Ligands and Coordination Chemistry Based on Vinyl and Alkynyl Substituted Pyrazoles

Der Naturwissenschaftlichen Fakultät der Friedrich-Alexander-Universität Erlangen-Nürnberg zur Erlangung des Doktorgrades Dr. rer. nat.

vorgelegt von Tobias Paul

aus Neuendettelsau

Als Dissertation genehmigt von der Naturwissen- schaftlichen Fakultät der Friedrich-Alexander-Universität Erlangen-Nürnberg

Tag der mündlichen Prüfung: 10. Juni 2015

Vorsitzender des Promotionsorgans: Prof. Dr. Jörn Wilms Gutachter: Prof. Dr. Nicolai Burzlaﬀ Prof. Dr. Julien Bachmann

Die vorliegende Arbeit entstand in der Zeit von November 2011 bis Dezember 2014 im Department für Chemie und Pharmazie (Lehrstuhl für Anorganische und Metallorganische Chemie) der Friedrich-Alexander-Universität Erlangen-Nürnberg unter der Anleitung von Prof. Dr. Nicolai Burzlaﬀ.

Früher starben die Menschen mit 35 Jahren, heute schimpfen sie bis 95 auf die Chemie.

Carl Heinrich Krauch

Contents

1 State of Knowledge 1 1.1 Scorpionate Ligands ...... 2 1.1.1 The History of Scorpionate Ligands ...... 2 1.1.2 Bis(pyrazol-1-yl)acetic Acids ...... 2 1.1.3 Bis(pyrazol-1-yl)methane Based Ligands ...... 4 1.2 Polymerizable Bis(pyrazolyl)acetic Acids ...... 7 1.2.1 Derivatives of Bis(pyrazolyl)acetic Acids ...... 7 1.2.2 Solid Phase Immobilization of Bis(3,5-dimethylpyrazol-1-yl)acetic acid ...... 8 1.2.3 Copolymerization Immobilization of Bis(3,5-dimethylpyrazol-1-yl)- acetic acid ...... 9 1.2.4 Bis(3,5-dimethyl-4-vinylpyrazol-1-yl)acetic acid (Hbdmvpza) . . . . 10 1.2.5 Immobilization of Hbdmvpza ...... 12 1.2.6 Metal Complexes of Hbdmvpza Based Copolymers ...... 13 1.3 Ferrocene as Building Block ...... 17 1.3.1 The History of Ferrocene ...... 17 1.3.2 Substitution Reactions of Ferrocene ...... 18 1.3.3 Transition Metal Catalyzed Cross-Coupling Reactions with Ferrocene 20 1.3.4 Negishi Type Coupling Reactions with Ferrocene ...... 21 1.3.5 Kumada Type Coupling Reactions with Ferrocene ...... 21 1.3.6 Sonogashira Type Coupling Reactions with Ferrocene ...... 21 1.3.7 Redox Properties of Ferrocene and its Derivatives ...... 24 1.3.8 Ferrocene Substituted Scorpionate Ligands ...... 26 1.4 The Rieske Dioxygenase ...... 30 1.4.1 Model Complexes of the Rieske Dioxygenase ...... 33 1.5 Molybdenum Containing Enzymes ...... 36 1.5.1 The Sulﬁte Oxidase ...... 37 1.5.2 The DMSO Reductase ...... 41 1.5.3 Model Complexes of the DMSO Reductase ...... 44 1.6 Coordination Polymers ...... 46 1.6.1 Building Blocks for Coordination Polymers ...... 46 1.6.2 Polyyne Bridged Coordination Polymers ...... 48 1.6.3 Pyrazole Based Ligands for Coordination Polymers ...... 50

i Contents

2 Objectives and Aims 53

3 Results and Discussion 57 3.1 Oxo-Transfer Catalysis by Chelate and Scorpionate Oxomolybdenum Com- plexes ...... 58 3.1.1 Bis(3,5-dimethyl-4-formylpyrazol-1-yl)methane (1)...... 59 3.1.2 Bis(3,5-dimethyl-4-vinylpyrazol-1-yl)methane (bdmvpzm) (2).... 60

3.1.3 [MoO2Cl2(bdmvpzm)] (3)...... 61 3.1.4 Bis(3,5-dimethyl-4-vinylpyrazol-1-yl)acetic acid (4)...... 63

3.1.5 [MoO2Cl(bdmvpza)] (5)...... 65 3.1.6 Copolymers containing bdmvpzm (2) and Hbdmvpza (4)...... 68 3.1.7 Molybdenum Containing Copolymers ...... 70

3.1.7.1 Treatment of Copolymers with [MoO2Cl2(THF)2]..... 70

3.1.7.2 Copolymerization of [MoO2Cl2(bdmvpzm)] (3) and

[MoO2Cl(bdmvpza)] (5)...... 73 3.1.8 Oxygen Atom Transfer Catalysis ...... 74 3.2 4-Ethynyl Substituted Pyrazole Based Ligands ...... 78 3.2.1 Bis(4-(2,2-dibromovinyl)-3,5-dimethylpyrazol-1-yl)methane (14).. 80 3.2.2 Bis(4-ethynyl-3,5-dimethylpyrazol-1-yl)methane (bedmpzm) (15)...... 81 3.2.3 Attempted Synthesis of Bis(4-trimethylsilyl-ethynyl-3,5-dimethylpyrazol-1-yl)acetic acid (16)...... 82 3.2.4 [CuI(bedmpzm)] (17)...... 83

3.2.5 [ZnCl2(bedmpzm)] (18)...... 84

3.2.6 [MnCl2(bedmpzm)2](19)...... 84

3.2.7 [CoCl2(bedmpzm)] (20)...... 85

3.2.8 [MoO2Cl2(bedmpzm)] (21)...... 86 3.2.9 4-Iodopyrazole (22) and 4-Iodo-3,5-dimethylpyrazole (23)..... 87 3.2.10 4-Iodo-1-tritylpyrazole (24) and 4-Iodo-3,5-dimethyl-1-tritylpyrazole (25)...... 87 3.2.11 3,5-Dimethyl-4-(trimethylsilyl)ethynyl-1-tritylpyrazole (26)..... 88 3.2.12 4-(Trimethylsilyl)ethynyl-1-tritylpyrazole (27)...... 89 3.2.13 3,5-Dimethyl-4-(trimethylsilyl)ethynylpyrazole (28)...... 90 3.2.14 2,2-Bis(4-ethynyl-3,5-dimethylpyrazol-1-yl)acetic acid (29)..... 91 3.2.15 (2-Hydroxyphenyl)-bis(3,5-dimethyl-4-(trimethylsilyl)ethynylpyrazol- 1-yl)methane [HOPhbdmeTMSpzm] (30)...... 92 TMS 3.2.16 [MoO2Cl2(HOPhbdme pzm)] (31)...... 93

ii Contents

3.2.17 (2-Hydroxyphenyl)-bis(3,5-dimethyl-4-ethynylpyrazol-1-yl)methane (32)...... 95 3.2.18 (1-Methylimidazol-2-yl)-bis(3,5-dimethyl-4-(trimethylsilyl)ethynylpyrazol-1-yl)methane (33)...... 96 3.2.19 (1-Methylimidazol-2-yl)-bis(3,5-dimethyl-4-ethynylpyrazol-1-yl)methane (34)...... 98 3.2.20 Summary of 4-Ethynyl Substituted Pyrazole Based Ligands . . . . 100 3.3 Coordination Polymers of 1,4-Bis(1H -pyrazol-4-yl)butadiynes ...... 101 3.3.1 3,5-Dimethyl-4-ethynyl-1-tritylpyrazole (35)...... 102 3.3.2 1,4-Bis(3,5-dimethyl-1-tritylpyrazole-4-yl)butadiyne (36)...... 103 3.3.3 1,4-Bis(3,5-dimethyl-1H -pyrazol-4-yl)butadiyne (37)...... 104 3.3.4 Poly(cobalt(II)acetylacetonato-bis(1,4-bis(3,5-dimethylpyrazol-4-yl)- butadiyne)) (38/39)...... 108 3.3.5 Poly(cobalt(II)chlorido-bis(1,4-bis(3,5-dimethyl-1H -pyrazol-4-yl)butadiyne)) (40)...... 111 3.3.6 4-Ethynyl-1-tritylpyrazole (42)...... 114 3.3.7 1,4-Bis(1-tritylpyrazol-4-yl)butadiyne (43)...... 114 3.3.8 Attempted Synthesis of 1,4-Bis(1H -pyrazol-4-yl)butadiyne (44).. 115 3.4 Ferrocene Based Models for Rieske Dioxygenases ...... 118 3.4.1 Bis(4-iodo-3,5-dimethylpyrazol-1-yl)methane (45)...... 120 3.4.2 Bis(4-iodopyrazol-1-yl)methane (46)...... 120 3.4.3 Bis(4-iodopyrazol-1-yl)acetic acid (47) and Bis(4-iodo-3,5-dimethylpyrazol-1-yl)acetic acid (48)...... 122 3.4.4 Methyl Bis(4-iodopyrazol-1-yl)acetate (49) and Methyl Bis(3,5-dimethyl-4-iodopyrazol-1-yl)acetate (50)...... 123 3.4.5 Bis(4-ethynylferrocenylpyrazol-1-yl)methane (befcpzm) (51).... 125 3.4.6 Methyl bis(4-ethynylferrocenylpyrazol-1-yl)acetate (mbefcpzac) (52)...... 128 3.4.7 Bis((4-ethynyl-1-ferrocenylphen-4-yl)-3,5-dimethylpyrazol-1-yl)methane (bepfcdmpzm) (53)...... 130 3.4.8 Methyl bis((4-ethynyl-1-ferrocenylphen-4-yl)pyrazol-1-yl)acetate (mbepfcpzac) (54)...... 133 3.4.9 Bis(3,5-dimethyl-4-(1-ferrocenyl-1,2,3-triazol-4-yl)pyrazol-1-yl)methane (bdmfctpzm) (55)...... 135 3.4.10 Bis(3,5-dimethyl-4-(1-methylferrocenyl-1,2,3-triazol-4-yl)pyrazol-1- yl)me-thane (bdmfcmtpzm) (56)...... 137 3.4.11 Summary of the Ferrocene Based Models for Rieske Dioxygenases . 140

iii Contents

4 Summary and Outlook 143

5 Zusammenfassung und Ausblick 151

6 Experimental Section 159 6.1 General Remarks ...... 160 6.1.1 Working Techniques ...... 160 6.1.2 Spectroscopic and Analytical Methods ...... 160 6.1.3 Destabilization of Copolymers ...... 162 6.1.4 Chemicals ...... 162 6.2 Oxo-Transfer Catalysis by Chelate and Scorpionate Oxomolybdenum Com- plexes ...... 164 6.2.1 Synthesis of Bis(3,5-dimethyl-4-formylpyrazol-1-yl)methane (1)... 164 6.2.2 Synthesis of Bis(3,5-dimethyl-4-vinylpyrazol-1-yl)methane (bdmvpzm) (2)...... 165

6.2.3 Synthesis of [MoO2Cl2(bdmvpzm)] (3)...... 166 6.2.4 Synthesis of Bis(3,5-dimethyl-4-vinylpyrazol-1-yl)acetic acid (Hbdmvpza) (4)...... 167

6.2.5 Synthesis of [MoO2Cl(bdmvpza)] (5)...... 168 6.2.6 Copolymerization of bdmvpzm (2) with MMA to form P6 ..... 169 6.2.7 Copolymerization of bdmvpzm (2) with EGDMA to form P7 .... 170 6.2.8 Copolymerization of Hbdmvpza (4) with MMA to form P8 ..... 171 6.2.9 Copolymerization of Hbdmvpza (4) with EGDMA to form P9 ... 172 6.2.10 Synthesis of P6-Mo ...... 173 6.2.11 Synthesis of P7-Mo ...... 174 6.2.12 Synthesis of P8-Mo ...... 175 6.2.13 Synthesis of P9-Mo ...... 176

6.2.14 Copolymerization of [MoO2Cl2(bdmvpzm)] (3) with MMA to form P10 ...... 177

6.2.15 Copolymerization of [MoO2Cl2(bdmvpzm)] (3) with EGDMA to form P11 ...... 178

6.2.16 Copolymerization of [MoO2Cl(bdmvpza)] (5) with MMA to form P12 ...... 179

6.2.17 Copolymerization of [MoO2Cl(bdmvpza)] (5) with EGDMA to form P13 ...... 180 6.3 4-Ethynyl Substituted Bis(pyrazolyl)methane Ligands ...... 181 6.3.1 Synthesis of Bis(4-(2,2-dibromovinyl)-3,5-dimethylpyrazol-1-yl)methane (14)...... 181

iv Contents

6.3.2 Synthesis of Bis(4-ethynyl-3,5-dimethylpyrazol-1-yl)methane (bedmpzm) (15)...... 182 6.3.3 Synthesis of [CuI(bedmpzm)] (17)...... 183

6.3.4 Synthesis of [ZnCl2(bedmpzm)] (18)...... 184

6.3.5 Synthesis of [MnCl2(bedmpzm)] (19)...... 185

6.3.6 Synthesis of [CoCl2(bedmpzm)] (20)...... 186

6.3.7 Synthesis of [MoO2Cl2(bedmpzm)] (21)...... 187 6.3.8 Synthesis of 4-Iodopyrazole (22)...... 188 6.3.9 Synthesis of 4-Iodo-3,5-dimethylpyrazole (23)...... 189 6.3.10 Synthesis of 4-Iodo-1-tritylpyrazol (24)...... 190 6.3.11 Synthesis of 4-Iodo-3,5-dimethyl-1-tritylpyrazole (25)...... 191 6.3.12 Synthesis of 3,5-Dimethyl-4-(trimethylsilyl)ethynyl-1-tritylpyrazole (26)...... 192 6.3.13 Synthesis of 4-(Trimethylsilyl)ethynyl-1-tritylpyrazole (27)..... 193 6.3.14 Synthesis of 3,5-Dimethyl-4-(trimethylsilyl)ethynylpyrazole (28).. 194 6.3.15 Synthesis of 2,2-Bis(4-ethynyl-3,5-dimethylpyrazol-1-yl)acetic acid (29)...... 195 6.3.16 Synthesis of (2-Hydroxyphenyl)-bis(3,5-dimethyl-4-(trimethylsilyl)- ethynylpyrazol-1-yl)methane [HOPhbdmeTMSpzm] (30)...... 196 TMS 6.3.17 Synthesis of [MoO2Cl2(HOPhbdme pzm)] (31)...... 197 6.3.18 Synthesis of (2-Hydroxyphenyl)-bis(3,5-dimethyl-4-ethynylpyrazol- 1-yl)methane (32)...... 198 6.3.19 Synthesis of (1-Methylimidazol-2-yl)-bis(3,5-dimethyl-4-(trimethylsilyl)ethynylpyrazol-1-yl)methane (33)...... 199 6.3.20 Synthesis of (1-Methylimidazol-2-yl)-bis(3,5-dimethyl-4-ethynylpyrazol-1-yl)methane (34)...... 200 6.4 Coordination Polymers of 1,4-Bis(1H -pyrazol-4-yl)butadiynes ...... 202 6.4.1 Synthesis of 3,5-Dimethyl-4-ethynyl-1-tritylpyrazole (35)...... 202 6.4.2 Synthesis of 1,4-Bis(3,5-dimethyl-1-tritylpyrazole-4-yl)butadiyne (36)...... 203 6.4.3 Synthesis of 1,4-Bis(3,5-dimethyl-1H -pyrazol-4-yl)butadiyne (37). 204 6.4.4 Synthesis of Poly(cobalt(II)acetylacetonato-bis(1,4-bis(3,5-dimethylpyrazol-4-yl)butadiyne)) (38/39)...... 205 6.4.5 Synthesis of Poly(cobalt(II)chlorido-bis(1,4-bis(3,5-dimethyl-1H -pyrazol-4-yl)butadiyne)) (40)...... 206 6.4.6 Attempted synthesis of Poly(cobalt(II)bromido-bis(1,4-bis(3,5-dimethyl-1H -pyrazol-4-yl)butadiyne)) (41)...... 207 6.4.7 Synthesis of 4-Ethynyl-1-tritylpyrazole (42)...... 208

v Contents

6.4.8 Synthesis of 1,4-Bis(1-tritylpyrazol-4-yl)butadiyne (43)...... 209 6.4.9 Attempted Synthesis of 1,4-Bis(1H -pyrazol-4-yl)butadiyne (44).. 210 6.5 Ferrocene Based Models for Rieske Dioxygenases ...... 211 6.5.1 Synthesis of Bis(4-iodo-3,5-dimethylpyrazol-1-yl)methane (45)... 211 6.5.2 Synthesis of Bis(4-iodopyrazol-1-yl)methane (46)...... 212 6.5.3 Synthesis of Bis(4-iodopyrazol-1-yl)acetic acid (47)...... 213 6.5.4 Synthesis of Bis(4-iodo-3,5-dimethylpyrazol-1-yl)acetic acid (48).. 214 6.5.5 Synthesis of Methyl bis(4-iodopyrazol-1-yl)acetate (49)...... 215 6.5.6 Synthesis of Methyl bis(4-iodopyrazol-1-yl)acetate (50)...... 216 6.5.7 Synthesis of Bis(4-ethynylferrocenylpyrazol-1-yl)methane (51)... 217 6.5.8 Synthesis of Methyl bis(4-ethynylferrocenylpyrazol-1-yl)acetate (52) 218 6.5.9 Synthesis of Bis((4-ethynyl-1-ferrocenylphen-4-yl)-3,5-dimethylpyrazol-1-yl)methane (53)...... 219 6.5.10 Synthesis of Methyl bis((4-ethynyl-1-ferrocenylphen-4-yl)pyrazol-1- yl)acetate (54)...... 220 6.5.11 Synthesis of Bis(3,5-dimethyl-4-(1-ferrocenyl-1,2,3-triazol-4-yl)pyrazol-1-yl)methane (55)...... 221 6.5.12 Synthesis of Bis(3,5-dimethyl-4-(1-methylferrocenyl-1,2,3-triazol-4- yl)pyrazol-1-yl)methane (56)...... 222 6.6 Oxygen Atom Transfer Catalysis ...... 224

Appendix 225 A Details of Structure Determinations ...... 226 B Abbreviations ...... 231 C List of Compounds ...... 235

Bibliography 237

Danksagung 251

1 State of Knowledge

1 1 State of Knowledge

1.1 Scorpionate Ligands

1.1.1 The History of Scorpionate Ligands

When S. Trofimenko synthesized ﬁrst hydro(trispyrazol-1-yl)borates in 1967, he laid the foundation for a whole new group of ligands.[1] These ligands are of the general form − [RR’B(pz)2] as depicted in ﬁgure 1.1. The pyrazole rings can either be unsubstituted or bear sterically more demanding moieties in the ring positions 3, 4 and 5. Such molecules with their three donor groups are excellent tripodal ligands and bind to metal centers in a facial κ3 fashion. The resulting complexes are of the general composition [RR’B(µ- [2] pz)2MLn].

R' R B M N N N N

Figure 1.1: Poly(pyrazolyl)borate ligands according to Trofimenko.[1]

The shape of those ligands, especially when coordinated towards a metal center reminded Trofimenko of a scorpion - with the pyrazole rings as the scissors and the third moiety as its sting. Hence he called those ligands scorpionate ligands. If the third donor is of the same kind as the other two, the term homoscorpionate ligands is used. If it is different, they are called heteroscorpionate ligands.[3] A first heteroscorpionate ligand bearing a sulfur donor group, was introduced by Ghosh et al. in 1998. In order to obtain this N,N,S binding motif, he used a thioether group as third donor moiety.[4] Despite the widespread applications that were found for these compounds, they still bore one drawback, namely their B-N bond, which is very sensitive towards hydrolysis.[5] First modifications of this concept were the exchange of the boron atom for other elements such as aluminum, indium, gallium or silicon. Such analogues could also change the charge of the resulting ligands.[3] The most prominent variation was however based on the bis- and tris(pyrazolyl)methane ligands, that have been known since 1937.[6–8] From there, Otero et al. started to synthesize the class of bis(pyrazol-1-yl)acetic acids.[9,10]

1.1.2 Bis(pyrazol-1-yl)acetic Acids

Those bis(pyrazol-1-yl)acetic acids were ﬁrst published in the late 90s. Otero et al. deprotonated bis(3,5-dimethylpyrazol-1-yl)methane with n-butyllithium and subsequently

2 1.1 Scorpionate Ligands reacted it with carbon dioxide, to obtain bis(3,5-dimethylpyrazol-1-yl)acetate (bdmpza) (see scheme 1.1).[9,10]

Li+

1. n-BuLi N N N N 2. CO 2 - 1/4 CO2 × H2O THF N N N N

Scheme 1.1: Synthesis of bis(pyrazolyl)acetato ligands according to Otero et al.[10]

Following this route, they were able to obtain N,N,O coordinating ligands in addition to the already known tris(pyrazolyl)methane ligands, which are N,N,N coordinating. How- ever this synthetic pathway only supports pyrazole precursors with substituents in ortho position. Without them, those positions would be deprotonated when n-butyllithium is applied. This problem was overcome by Burzlaff et al. in an attempt to simplify the synthesis of Hbdmpza from a three step synthesis under nitrogen atmosphere[10] to a nonsensitive one pot synthesis in 2001.[11]

O OH R 1. KOH, K CO R R Br O 2 3, NH TEBA 2 + 2. HCl N N N Br OH THF N N R R = H (bpzaH) R R R = Me (bdmpzaH)

Scheme 1.2: One pot synthesis of bis(pyrazol-1-yl)acetic acids according to Burzlaff et al.[11]

To do so, they deprotonated the desired pyrazole derivatives with potassium carbonate and potassium hydroxide in the presence of a phase transfer catalyst like benzyltriethylammonium chloride and dibromo- or dichloroacetic acid, to obtain the corresponding bis(pyrazol-1-yl)acetic acid after acidiﬁcation (see scheme 1.2).[11,12] Complexes of the middle and late transition metals of those ligands were published from there on. Apart from their apparent use for coordination chemistry,[11–13] their tripodal facial N,N,O coordination motif enables them to serve as model system for metalloenzymes that feature the frequently found “2-His-1-carboxylate facial triade” motif at their active site (see ﬁgure 1.2).[14,15]

3 1 State of Knowledge

Glu/Asp O N N His O His N N M X X X Figure 1.2: 2-His-1-carboxylate-triade, X = water/substrate.

1.1.3 Bis(pyrazol-1-yl)methane Based Ligands

At the same time, a diﬀerent approach was pursued by Higgs et al. They published N,N,O and N,N,S κ3-coordinating bis(pyrazol-1-yl)methane ligands, starting from bis(pyrazol- 1-yl)ketone.[16,17]

R3 R4

1 O 1 Y OH R1 R R R1 R1

NH Et3N/COCl2 N N O H N N THF N N N CoCl2 N N - CO2 R2 R2 R2 R2 R2 R1 = H, Me R3 = H, Me R2 = H, Me, i-Pr R4 = H, Me, i-Pr Y = OH, SCN

Scheme 1.3: Synthesis of a N,N,O coordinating heteroscorpionate ligand according to Carrano et al.[16,17]

Therefore, they deprotonated the pyrazole with triethylamine in order to subsequently react it with phosgene to obtain the corresponding keto compound (see scheme 1.3). This initial step was ﬁrst published by Byers et al. By this means, it is possible to turn any pyrazoles into the corresponding keto compounds, allowing it to inﬂuence the sterical demand of the resulting compounds.[18] The following cobalt catalyzed step was inspired by a reaction, which was published by Peterson and Thé in 1973 and leads to a metal catalyzed rearrangement at the bridging carbon atoms of bis(pyrazol-1-yl)ketones with aldehydes or ketones to the corresponding bis(pyrazol-1-yl)methanes and carbon dioxide.[19–21] The thiocyanate derivative was reacted further with lithium aluminum hydride to reduce the thiocyanate moiety to a thiol, since the direct synthesis of the thiophenol based ligand was not possible due to the high reactivity of thiols.[17] For easier handling, the problematic use of phosgene was abandoned by Artaud and Burzlaff and replaced by solid triphosgene.[22,23] Yet Reger et al. could further re-

4 1.1 Scorpionate Ligands duce the toxicity of the reaction by employing thionyl chloride to create a sulﬁnyl bridge between the pyrazoles. This leads to the formation of a 1,1’-sulﬁnylbispyrazole, which can, under release of sulfur dioxide, be turned over in the same way as the corresponding keto compounds (see scheme 1.4).[24–26]

O R R S NH NaH/SOCl2 N N O H N N THF N N N CoCl2 N N - SO2

Scheme 1.4: Modiﬁed Peterson reaction according to Reger et al.[24–26]

Inspired by the results of Higgs et al. and Rebek et al.[16,27], the above concepts were further used by Elflein et al. in a reaction pathway, which initially aimed at the synthesis of chiral heteroscorpionate ligands. First ligands of this class were published by Tolman and coworkers[28] and Oter et al.[29] Burzlaff and coworkers were able to ﬁnd a one pot synthesis for such compounds based on bis(pyrazol-1-yl)methane and could synthesize a whole library of N,N,N and N,N,O as well as N,N,S coordinating ligands.[30]

O R1 R1 R1 1. 2 NaH S NH 2. SOCl2 N N 2 R2 R2 R2 N - 2 NaCl N N

R3 R3 R3

O O pyridine, - SO2 Cl3C CCl3 R4 O O

O O R4 R1 R1 R1 R1 R4 N N CoCl2 or pyridine N N R2 R2 R2 R2 N N - CO2 N N

R3 R3 R3 R3

Scheme 1.5: One pot synthesis of bis(pyrazol-1-yl)methane based ligands according to Elflein et al.[23]

Originally, camphorpyrazole was reacted with phosgen and later trisphosgen as stated above.[22] In a next step the aforementioned modiﬁed Peterson reaction with salicy- ladehyde was carried out. (see scheme 1.5).[23]

5 1 State of Knowledge

However, this reaction pathway led to erratic yields, when sterically demanding hindered pyrazoles were used.[23] Such problems are known for Peterson rearrangements with sterically hindered pyrazoles.[20] Therefore the synthesis was altered to the ﬁnal one pot synthesis based on publications of Byers et al. and Reger et al.[18,26] One the one hand, the cobalt catalyst was omitted in favor of pyridine. This led to reproducible yields of up to 70 %. On the other hand, thionyl chloride was used as bridging agent, as was shown before (see scheme 1.4). Furthermore, the intermediate sulﬁnyl bridged species was not isolated. After treating the pyrazole derivatives with sodium hydride and thionyl chloride, the mixture was reacted with salicylaldehyde and pyridine without workup, delivering the desired ligand yields of up to 60 % (see scheme 1.5).[23] As mentioned before, this procedure led to the synthesis of a wide range of new chiral and achiral heteroscorpionate ligands, since any desired aldehyde and pyrazole derivatives can be used in this reaction.[30,31] This concept was adopted up by Hoffmann et al. Apart from the synthesis of several new ligands from the mentioned synthesis with aldehydes, it was found that also keto bridged compounds can be employed in this reaction pathway without altering the reaction conditions. By doing so, it was possible to obtain (2-pyridinyl)(phenyl)[bis(3- phenylpyrazolyl)]methane from 3-phenylpyrazole and benzoyl pyridine.[31]

6 1.2 Polymerizable Bis(pyrazolyl)acetic Acids

1.2 Polymerizable Bis(pyrazolyl)acetic Acids

1.2.1 Derivatives of Bis(pyrazolyl)acetic Acids

As mentioned before, bis(pyrazolyl)acetic acids, and especially the bis(3,5-dimethylpyrazol- 1-yl)acetic acid (bdmpza), were quickly adopted by Burzlaff et al. for their N,N,O binding motif, which closely resembles the “2-His-1-carboxylate triade”, which is found in a broad range of metalloenzymes.[14,15] Furthermore, they were readily available via the one pot synthesis shown in chapter 1.1.2. Searching for model complexes of iron and zinc enzymes, it was observed, that, due to the high coordination potential of bdmpza combined with the low sterical demand, complexation of iron(II) and zinc(II) chlorides with bdmpza led to the formation of bisligand complexes with two equivalents of bdmpza coordinated to one metal center (see ﬁgure 1.3).[12]

Figure 1.3: Molecular structure of the bisligand complex of ZnCl2 with bdmpza according to Beck et al.[12]

Of course this double coordination is undesired, since the active site of the resulting model enzyme is eﬀectively inhibited by the second coordinated ligand. It was expected, that this behavior could be overcome by an increase of the sterical demand of bdmpza. Therefore, the methyl substituents of the pyrazole rings, were exchanged for tert-butyl groups, what indeed led to the required singular coordination. The resulting zinc complex is depicted in ﬁgure 1.4. Unfortunately, the increased sterical demand also made the application of the one pot synthesis impossible, thus it was necessary to fall back to the original synthetic route of Otero et al. (see scheme 1.1).[10,12] Furthermore, it was possible to obtain chiral

7 1 State of Knowledge complexes by using two diﬀerently substituted pyrazole moieties. Upon introduction of the carboxylate function, a chiral center is formed at the methylene bridge.[32]

Figure 1.4: Molecular structure of the bisligand complex of ZnCl2 with bdtbpza according to Beck et al.[12]

Nevertheless, this concept could not be extended to all bio relevant transition metals. The reaction with some metals, such as copper, still leads to the formation of bisligand or even dinuclear complexes. Apart from this, those sterically demanding ligand could inﬂuence the reactivity of the resulting transition metal centers.[12,33]

1.2.2 Solid Phase Immobilization of bdmpza

In an effort to overcome these drawbacks, Burzlaff and coworkers adapted the concept of immobilization for bdmpza. In a first attempt, an allyl linker group was introduced at the bridging carbon atom, which allowed for the solid phase fixation of the ligand. The attachment of the ligand to an mercaptopropyl-silica matrix inhibited the formation of bisligand complexes, while keeping the original κ3-N,N,O binding motif intact. As depicted in scheme 1.6, it was possible to obtain the corresponding rhenium and manganese complexes. The tripodal coordination was thereby kept intact, as was proven by IR spectroscopy.[34]

8 1.2 Polymerizable Bis(pyrazolyl)acetic Acids

O OH CO H 1. LDA, THF 2 2. H2C=CH-CH2Br N N 3. H+ N N N N N N

1. KOtBu, THF

2. [MBr(CO)5] OR S O Si O OR O Si O N N SH N N O O O O N N N N M M OC CO OC CO CO CO Scheme 1.6: Solid phase ﬁxation of Mn and Re complexes on a mercaptopropyl-silica matrix by Hübner et al.[34]

1.2.3 Copolymerization Immobilization of bdmpza

As an alternative to the solid phase ﬁxation presented before, a second linker type with the capability to be copolymerized in a vinylogous polymerization reaction was developed. This hydroxymethyl linker was introduced at the methine bridge as well.[33] Apart from the aforementioned prevention of bisligand formation by withdrawing the ligand’s free mobility, this procedure provides another advantage. By using techniques of molecular imprinting, it is possible to create cavities in the resulting polymer.[33,35] To do so, dummy substrates are bound to the metal center of the complex prior to copolymerization. After the embedment of the complex in the polymer, those dummy substrates are removed, leaving stable cavities at the active sites. These cavities are similar to the substrate pockets of natural enzymes.[36–42] This technique can however only resemble the shape of such a cavity, thus increasing the substrate selectivity, whereas a real enzyme provides a wide range of especially hydrogen bonds, which support the catalytic activity of the enzyme. The synthesis of this hydroxymethyl substituted bdmpza derivative is depicted in scheme 1.7. The vinylogous copolymerization reaction can easily be initialized by a radical starter. For rhenium and manganese complexes, this copolymerization step can be carried either prior or after the complexation of metal fragments. Transition metals like copper, which tend to form bisligand complexes do however still do so, if the complexation is carried out

9 1 State of Knowledge

O OH OH 1. LDA, THF CO2H 2. (HCHO)n + N N 3. H / H2O N N N N N N

O 1. LDA, THF CO2H 2. (HCHO)n + 3. H / H2O N N N N

Scheme 1.7: Synthesis of a copolymerizable bdmpza derivative by Hübner et al.[33] before the polymerization. However, in any case, the original N,N,O binding motif was kept intact.[33]

1.2.4 Bis(3,5-dimethyl-4-vinylpyrazol-1-yl)acetic acid (Hbdmvpza)

Unfortunately, this concept soon reached its limit with respect to metal fragments with bulky substituents as for example [RuCl2(PPh3)3]. Depending on the desired substrate, such bulkier fragments are necessary to create a cavity large enough for catalytic application.

1. POCl3, DMF O O N N N N 2. H2O N N N N

"Ph3P=CH2" O OH 1. n-BuLi 2. CO2 N N 3. H+ N N N N N N

Scheme 1.8: Synthesis of a copolymerizable bdmpza derivative by Türkoglu et al.[35]

Due to the inﬂuence of the linker group located at the methine bridge on the coordination site, complexation of such fragments is inhibited. Furthermore, the low rigidity of the

10 1.2 Polymerizable Bis(pyrazolyl)acetic Acids linker group constitutes another drawback. On the one hand, it can cause chirality and thus enantiomers by dynamic interconversions.[33] On the other hand, the linker group tends to coordinate towards the metal center, thus replacing the carboxylate donor. For these reasons, it was attempted to move the linker group away from the coordination site of the ligand. As the most distant is position 4 of the pyrazole rings, a variation with a vinyl group was attempted in this position.[35]

[35] Figure 1.5: Molecular structure of [Mn(bdmvpza)(CO)3].

As depicted in scheme 1.8, the ligand synthesis started from bis(3,5-dimethylpyrazol- 1-yl)methane, which is readily available from 3,5-dimethylpyrazole in a phase transfer reaction.[43] The resulting methylene bridged compound is then turned over in a Vilsmeier- Haack formylation to obtain the corresponding bisaldehyde derivative, as reported by Potapov et al.[44] The next step consists of a Wittig reaction to introduce the desired vinyl linkers. The ﬁnal N,N,O binding motif is achieved by deprotonation of the methylene bridge with n-butyllithium and subsequent treatment with carbon dioxide followed by aqueous workup. Several transition metal complexes of the resulting Hbdmvpza ligand could be obtained by deprotonation of the carboxylate moiety with potassium tert-butoxide and the desired metal fragment. Since the coordination site is not inﬂuenced by the linker groups, the coordination of carbonyl fragments as well as reactions with bulky precursors as

[RuCl2(PPh3)3] were possible. The IR spectra recorded from the resulting complexes revealed almost identical absorption bands as similar κ3-N,N,O coordinated bis(pyrazol- 1-yl)acetato complexes, which have been studied in the past. In combination with X-ray structure determination (see figures 1.5 and 1.8), an influence of the linkers on the coordination site could be ruled out and the original binding motif could be verified.[11,33,35]

11 1 State of Knowledge

1.2.5 Immobilization of Hbdmvpza

As mentioned before, the most important feature of Hbdmvpza is its capability to form copolymers in a vinylogous copolymerization reaction. For this purpose, methyl methacrylate (MMA) and ethylene glycol dimethacrylate (EGDMA) were used as copolymers. It is also possible to polymerize the sole ligand to form a homopolymer by the same procedure. The resulting copolymer structures are depicted in ﬁgure 1.6.[35]

x y z O O NN NN

CO2H CO2H N N N N

x y z O O NN NN

CO2H CO2H N N O O N N

Figure 1.6: Molecular structures of Hbdmvpza copolymers with MMA (top) and EGDMA (bottom) according to Türkoglu et al.[35]

The composition of the resulting compound could be determined by elemental analysis. Since nitrogen is only contained in the ligand moieties, the nitrogen value enables the calculation of the ligand content of the copolymer.[35] Such an analysis of the homopolymer led to a value of 3.05 mmol/g polymer. Copoly- merization with MMA on the other hand led to the formation of two different fractions: The first fraction precipitated directly from solution during the polymerization process and was characterized by a high ligand incorporation of 0.746 mmol/g. On the contrary, the second fraction had to be precipitated from the reaction solution with methanol and exposed a significantly lower amount of ligand incorporation of only 0.304 g/mmol.[35]

12 1.2 Polymerizable Bis(pyrazolyl)acetic Acids

It was assumed, that the highly reactive crosslinking ligand molecules preferably reacted with each other, as long as their concentration was suﬃciently high. Therefore, highly crosslinked polymers were formed in the early phase of the reaction, which then precipitated because of their low solubility.[35,45] This theory was supported by the results of the reaction with EGDMA, which is a crosslinker itself. In this case, the resulting copolymer directly precipitated from solution with a ligand incorporation of 0.371 mmol/g. Since the feedstock contained ligand monomers in a concentration of 0.302 mmol/g, both components of the reaction showed a similar reactivity.[35] The exact polymer structure could not be determined. However, since free radical polymerization was used in the process, atactic arrangement has to be assumed in both cases. The size distribution for the soluble MMA copolymers could be determined to be between 5 × 103 g/mol and 1 × 107 g/mol. Whether these measurements derived from long single chains or several shorter chains, crosslinked by ligand moieties remained unclear. How- ever, the broad mass distribution range was most likely caused by random crosslinking of both of these units.[35]

1.2.6 Metal Complexes of Hbdmvpza Based Copolymers

It was expected, that the copolymerized Hbdmvpza ligand would bond to metal fragments in the same κ3-N,N,O fashion, as it was observed for the free ligand. In order to verify this behavior, the copolymers were reacted with manganese and rhenium pentacarbonyl bromides.[35]

O OH EGDMA / MMA EGDMA / MMA

1. KOtBu

N N 2. [MBr(CO)5] N N O O N N N N M EGDMA / MMA EGDMA / MMA OC CO CO

Scheme 1.9: Complexation of manganese and rhenium tricarbonyl fragments into the EGDMA and MMA copolymers. (M = Mn/Re).[35]

To do so, the insoluble polymers were treated with potassium tert-butoxide and charged with the corresponding carbonyl compounds, as depicted in scheme 1.9. In order to verify the coordination motif, the resulting compounds were examined via IR spectroscopy. Therefore, nujol mulls of the four polymers (Mn-EGDMA, Mn-MMA, Re-EGDMA and Re-MMA) were manufactured and analyzed. The two corresponding monomeric carbonyl

13 1 State of Knowledge

complexes [Mn(bdmvpza)(CO)3] and [Re(bdmvpza)(CO)3] were used as references for a successful N,N,O coordination.[35] As can be seen in figure 1.7, the spectra of the polymer embedded complexes (figure 1.7 b,c,e,f) agreed well with the reference spectra (figure 1.7 a, d), thus confirming the desired coordination mode. The reaction product of polymethylmethacrylate (PMMA) with [ReBr(CO)5] was used as control experiment and did not exhibit any of the desired vibrations (figure 1.7 g).[35]

Figure 1.7: IR spectra of (a) [Mn(bdmvpza)(CO)3](THF), (b) Mn-EGDMA (nujol), (c) Mn-EGDMA (nujol), (d) [Re(bdmvpza)(CO)3](THF), (e) Re-MMA (nujol), (f) Re-EGDMA (nujol), (g) control experiment with PMMA and [35] [ReBr(CO)5] (nujol).

However, non of the methods employed so far could determine the overall metal content of the resulting compounds, since it was unlikely, that every coordination site would be occupied after the complexation. Therefore, atomic absorption spectroscopy (AAS) was used in the case of manganese containing polymers and inductively coupled plasma atomic emission spectroscopy (ICP-AES) in the case of the rhenium containing polymers. An overview over the results is given in table 1.1. In general, the metal contents of the

14 1.2 Polymerizable Bis(pyrazolyl)acetic Acids

Polymer Metal/polymer Metal/polymer Occupied ligand sites [mg/g] [mmol/g] [%] Mn-MMA 25.8 0.470 63 Re-MMA 57.9 0.311 42 Mn-EGDMA 8.10 0.148 40 Re-EGDMA 7.11 0.038 10

Table 1.1: Metal content of the copolymers by Türkoglu et al.[35]

MMA copolymers were considerably higher than those of the corresponding EGDMA polymers. Since EGDMA as a crosslinker leads to a much denser polymer structure, than the MMA polymers, which are crosslinked at the ligand moieties only, it is more diﬃcult for metal fragments to reach the actual coordination sites. Thus, the lower sterical hindrance of the MMA copolymers leads to higher metal loadings.[35]

[35] Figure 1.8: Molecular structure of [Cu(bdmvpza)2] as shown by Türkoglu et al.

Finally, after having shown, that the original κ3-N,N,O binding motif was kept intact at the polymerized ligand bonding sites, it was necessary to investigate, if the formation of bisligand complexes could be effectively avoided by means of copolymerization of Hbdmvpza. Since the so far used precursor [MnBr(CO)5] reacts with this ligand to the 1:1 complex [Mn(bdmvpza)(CO)3], which is depicted in figure 1.5, copper(II) acetate was used. This salt was known to form bisligand complexes from experiments with bdmpza and did so when reacted with Hbdmpza under formation of a blue complex (see figure 1.8).[35]

15 1 State of Knowledge

To obtain a 1:1 copper polymer, the MMA copolymer was deprotonated with potassium tert-butoxide and treated with copper(II) chloride. The resulting compound was filtered off and washed thoroughly with methanol to obtain the desired product as a green powder (Cu-MMA).[35] To achieve an insight in the coordination of the copper salt to the polymer, UV/Vis spectra of both Cu-MMA and the monomeric bisligand complex [Cu(bdmvpza)2] were compared, as it is depicted in figure 1.9. The polymer could be analyzed by creating polymer pellets of Cu-MMA in a hydraulic press, which were made transparent by a drop of mineral oil.

Figure 1.9: UV/Vis spectra of (a) [Cu(bdmvpza)2] in methanol and (b) Cu-MMA (polymer pellet, nujol) by Türkoglu et al.[35]

As can be seen from the ﬁgure, a bathochromic shift of the absorption maximum by 64 nm was determined for Cu-MMA. These ﬁndings agreed well with measurements of the corresponding copper polymers of the methacryloxy-substituted ligand, which was presented above (see chapter 1.2.3).[33,35] This bathochromic shift strongly indicated the formation of one-sided κ3-N,N,O coordinated copper centers and therefore 1:1 complex moieties in the polymer. Nevertheless, other coordination modes like κ2-N,O could not be excluded entirely.[35]

16 1.3 Ferrocene as Building Block

1.3 Ferrocene as Building Block

1.3.1 The History of Ferrocene

Ferrocene was first synthesized by T. J. Kealy and P. L. Pauson in 1951 when they were trying to find a synthesis for fulvalene by reacting cyclopentadienylmagnesium bromide with ferric chloride. Instead they obtained an up till then unknown orange compound, which they called dicyclopentadienyl iron. The first striking feature of the new substance was its remarkable stability which they accounted to resonance structures (see figure 1.10 (i)).[46] First insight into molecular structure was brought by infrared studies of G. Wilkinson and R. B. Woodward. From their data, they proposed the correct structure for the new compound (see figure 1.10 (ii)) and also its final name ferrocene (Fc).[47] The proof for their proposal was first delivered by E. O. Fischer and W. Pfab and later in more detail by Dunitz et al. via X-ray structure analysis.[48]

Fe Fe2+ Fe

(i) (ii)

Figure 1.10: (i) First proposed mesomeric structures of ferrocene by T. J. Kealy and P. L. Pauson from 1951.[46]; (ii) Actual structure of ferrocene by G. Wilkin- son and R. B. Woodward.[47]

Since then, ferrocene became more and more important in organometallic chemistry. A wide range of applications was found during the last 60 years. On the one hand it can serve as a tunable electron reservoir in ligands for transition metal complexes, since its redox properties are strongly influenced by its chemical environment.[49] Heterocyclic ferrocene derivatives on the other hand are of special interest due to their remarkable photophysical,[50] magnetic,[51] and redox properties.[52] Another field with great potential for the application of ferrocene derivatives is the medicinal chemistry, especially in the field of cancer research in particular breast cancer. The biological activity of well-established drugs can be increased and their broad spectrum enhanced by the addition of ferrocene moieties.[53] The fact that ferrocene moieties have such an influence on the reactivity of its derivatives,[54] makes it interesting to implement it in different compounds to study the resulting effects and electronic properties.

17 1 State of Knowledge

1.3.2 Substitution Reactions of Ferrocene

In order to synthesize different ferrocene derivatives, it was first necessary to find suitable ways to substitute ferrocenes. Unfortunately, direct nitrations are not possible, since ferrocene would be oxidized simultaneously.[55] The cyclopentadienyl rings are however accessible for a wide range of reactions that are known from classical organic aromatic chemistry. These include acylation,[56] borylation,[56] mercuration,[57] and lithiation.[58] These pathways and the nucleophilic substitution reactions towards bromoferrocene and ferrocenylboronic acid are depicted in scheme 1.10.

HgCl Fe

Hg(OAc)2 NBS LiCl

n-BuLi or Li Br t-BuLi Tosylbromide Fe Fe Fe

B(OnBu)3, BBr3 H2O Acetlychloride AlCl3 BBr B(OH) 2 H O 2 Fe 2 Fe O

Scheme 1.10: Functionalization routes of ferrocene towards bromoferrocene and ferrocenylboronic acid.[56–59]

The shown conversions are of special importance because bromo- and iodoferrocene are educts for a wide range of subsequent reactions. Those compounds can be obtained by several synthetic pathways. As can be seen in scheme 1.10, it is possible to react ferrocene with mercury acetate followed by the addition of a lithium halide like lithium chloride or bromide, to yield the corresponding halomercury derivative as it was shown by Fish and Rosenblum Treatment of the monosubstituted species with N -bromosuccinimide (NBS) leads to the formation of bromoferrocene.[57] An alternative reaction pathway is initial functionalization of ferrocene with n-butyllithium and N,N,N’,N’-tetramethylethylenediamine or t-butyllithium at low temperatures, thus avoiding the formation of dilithiated products or cross reactions with solvents. Sub-

18 1.3 Ferrocene as Building Block sequent treatment with tosyl bromide leads to the formation of bromoferrocene.[58] Kamounah et al. on the other hand pursued a diﬀerent approach. Reacting ferrocene with boron tribromide yields dibromoborylferrocene, which can easily be hydrolyzed to fer- roceneboronic acid. From there, either a Suzuki coupling reaction with halide-substituted aromatic compounds or the reaction to iodoferrocene by application of N -iodosuccinimide (NIS) can be carried out (see scheme 1.11).[59]

B(OH) I 2 N-iodosuccinimide Fe Fe

Scheme 1.11: Iodination of ferrocenylboronic acid.[59]

Starting from bromoferrocene, it was possible to functionalize ferrocene with a range of diﬀerent moieties via copper(I) promoted Ullmann reactions. By this way a variety of N -, O- and S donor groups could be introduced as depicted in scheme 1.12.[60]

OPh OC(O)CH3 Fe Fe

NaOPh NaOAc CuCl CuCl

NaSPh KCN SPh Br CN CuCl CuCl Fe Fe Fe

NaN3 CuCl

N3 LiAlH4 NH2 Fe Fe

Scheme 1.12: Functionalization of bromoferrocene via copper(I) promoted Ullmann reactions.[60]

19 1 State of Knowledge

1.3.3 Transition Metal Catalyzed Cross-Coupling Reactions with Ferrocene

Advances in transition metal catalyzed homo and hetero coupling reactions made it possible to proceed from the above mentioned C-X connected ferrocene derivatives to C-C bonded aromatic systems. Among them are monodentate building blocks, which feature N donor functions like ferrocenylpyridines,[61] ferrocenylpyrazoles,[62–64] ferrocenylpyrim- idines,[65,66] ferrocenylpyrazine, ferrocenylimidazoles,[67] and ferrocenyltriazoles[63,68,69] (see ﬁgure 1.11).

N NH Fe N Fe N Fe N (i) (ii) (iii)

N N N N N Fe Fe Fe N (iv) (v) (vi)

N N N N N Fe N Fe N Fe (vii) (viii) (ix)

Figure 1.11: Heteroaryl substituted ferrocene derivatives: (i) ferrocenylpyridine, (ii) ferrocenylpyrazole, (iii) 2-ferrocenyl-4,6-dimethylpyrimidine, (iv) N- ferrocenylpyrazole, (v) N-ferrocenyl-3,5-dimethylpyrazole, (vi) 2-ferrocenylpyrazine, (vii) 5-ferrocenylpyrimidine, (viii) 4-ferrocenylpyrimidine, (ix) 1- ferrocenyl-1,2,3-triazole.[61–64,66,68,69]

While 3-ferrocenylpyrazoles were obtained by a diﬀerent approach starting from acetyl- ferrocene,[70] N donor ferrocene derivatives are generally accessible by copper mediated Ullmann type substitution reactions.[62,63] However, ferrocene triazoles are synthesized via the copper(I)-catalyzed Azide-Alkyne Cycloaddition (CuAAC).[68,69] The remaining C-C coupled ferrocene compounds are obtained by Kumada or Negishi coupling reactions as will be shown in the next sections.

20 1.3 Ferrocene as Building Block

1.3.4 Negishi Type Coupling Reactions with Ferrocene

To perform a Negishi type C-C coupling reaction, it is ﬁrst necessary to lithiate ferrocene with t-butyllithium at low temperatures. Subsequent addition of zinc(II) chloride leads to a transmetallation reaction, thus forming ferrocenyl zinc chloride, as shown by Mochida et al. The actual coupling step with an appropriate aryl halide such as 5-bromopyrimidine or 4-iodo-1-tritylpyrazole is catalyzed by a palladium catalyst like bis(triphenylphosphine)palladium dichloride. This way, ferrocenylpyrimidine and ferrocenylpyrazole can be obtained as depicted in scheme 1.13.[64,71]

N [PdCl2(PPh3)2] Fe 5-bromopyrimidine

1. t-BuLi ZnCl 2. ZnCl2 Fe Fe

Trt N N [PdCl2(PPh3)2] 4-iodo-1-tritylpyrazole Fe

Scheme 1.13: Reaction pathway of Negishi type coupling reactions with ferrocene towards 5-ferrocenylpyrimidine and 4-ferrocenyl-1-tritylpyrazole.[64,71]

1.3.5 Kumada Type Coupling Reactions with Ferrocene

Another applicable cross coupling reaction is the Kumada coupling reaction. It starts from bromoferrocene, which has to be transformed into a Grignard reagent in the ﬁrst place. The resulting ferrocenyl magnesium bromide is reacted with an arylbromide in the presence of a nickel(II) catalyst like Dichlorido[bis(1,3-diphenyl-phosphino)pro- pane]nickel(II). The resulting compound is the corresponding ferrocenylarene, as can be seen in scheme 1.14.[71]

1.3.6 Sonogashira Type Coupling Reactions with Ferrocene

The last cross coupling reaction to be considered here is the Sonogashira coupling reaction. This palladium(0) catalyzed reaction was ﬁrst reported by Sonogashira et al. in 1975 and has found a wide range of applications since then.[72] The reaction in general

21 1 State of Knowledge

N 3-bromopyridine Fe [NiCl2(dppp)]

MgBr 4-bromopyridine N [NiCl2(dppp)] Fe Fe

4-bromopyridine Fe N [NiCl2(dppp)]

Scheme 1.14: Reaction pathway of Kumada type coupling reactions with ferrocene towards ferrocenylpyridines.[71] creates a C-C bond between an terminal alkyne and an organic halide. In contrast to the other coupling reactions presented thus far, the two coupling partners are not directly bound by a single bond, but instead there is always at least an ethynyl moiety between them, serving as a linker group.

CO2Me

CO2Me [Pd(PPh3)2Cl2] CuI, NEt3, RT N Fe + X Fe N

X = Cl / Br

Scheme 1.15: Reaction pathway of Sonogashira type coupling reactions with ethynylferrocene.[73]

To perform the coupling reaction with a ferrocene derivative and a heterocycle, two different educt combinations are feasible. It is possible to start with a ferrocene halide and a heteroarylacetylene and vice versa. However, as stated by Torres et al. the ﬁrst educt combination leads to very low yields in the case of ferrocene. Therefore Torres used ethynylferrocene in combination with diﬀerent haloheterocycles and obtained yields of up to 96 % (see scheme 1.15).[73]

22 1.3 Ferrocene as Building Block

Following this procedure a variety of diﬀerent ferrocenylethynyl substituted heterocycles were accessible. A selection of them is presented in ﬁgure 1.12.[73–75]

Fe Fe

Fe Fe N (i) (ii)

n-Bu Bu-n B N N R R N N Fe B Fe n-Bu Bu-n (iii)

N N N HCl Fe (v) (iv)

Fe Fe

Figure 1.12: Ethynylferrocene substituted heterocycles. (i) 2,6-ferrocenylethynyl- pyridine, (ii) 3,4-Bis(ferrocenylethynyl)-N-phenylpyrrole, (iii) ferrocenyl pyrazaboles (R = varying spacer groups, see ﬁgure 1.13) (iv) 4- ferrocenylethynyl-pyridine hydrochloride, (v) bis-6,6’-(ferrocenylethynyl)- 2,2’-bipyridine.[73–75]

The most interesting compounds for this work are the group of the ferrocenyl pyrazaboles (ﬁgure 1.12 (iii)) by Misra et al., which are the only literature known 4-ferrocenylethynyl- pyrazole derivatives. The spacer groups used by this workgroup are mainly phenyl rings conjugated with ethynyl or vinyl groups. By doing so, they tried to inﬂuence the electrochemical potential of the corresponding ferrocenyl pyrazaboles.[75]

23 1 State of Knowledge

1.3.7 Redox Properties of Ferrocene and its Derivatives

Pure ferrocene has a redox potential of +400 mV against standard hydrogen electrode (SHE).[76] However, this potential can be easily influenced by the chemical environment of the ferrocene moiety, for example by the introduction of different substituents.[52] Mochida et al. examined the influence of pyrazole substituents on the redox properties of ferrocene and found for 4-ferrocenyl-1-tritylpyrazole (see scheme 1.13) a shift of the electrochemical potential to E1/2 = −0.03 V, which was found as a quasi reversible redox process by cyclovoltammetry. After deprotection of this compound with trifluoroacetic + [77] acid they obtained 4-ferrocenylpyrazole with E1/2 = −0.04 V (acetonitrile, vs. Fc/Fc ). While this may seem to be only a minor adjustment in the electrochemical potential of the resulting ferrocenyl compounds, the fact, that the half wave potential is shifted towards more negative values is still noteworthy, since other heteroaryl compounds differ greatly in this behavior: 4-, 3-, and 2-ferrocenylpyridine for example alter the redox potential + of the ferrocene moieties to E1/2 = +0.206 V, +0.168 V and +0.155 V vs. Fc/Fc , [61] + respectively. 5-Ferrocenylpyrimidine (E1/2 = +0.14 V vs. Fc/Fc ), 4-ferrocenyltriazole + + (E1/2 = +0.21 V vs. Fc/Fc ) and 4-ferrocenyltetrazole (E1/2 = +0.27 V vs. Fc/Fc ) exhibit higher half wave potentials than pure ferrocene as well.[64]

a) Fc b) Fc n-Bu Bu-n R = B N N R R N N c) Fc d) B n-Bu Bu-n Fc

e) Fc f) Fc

Fc g)

Figure 1.13: Series of ferrocenyl pyrazaboles by Misra et al.[75]

In general, the redox potential tends towards more negative values, if the size of the aromatic backbone, to which the ferrocene moiety is bonded, is increased. The system

Fc(CH=CH)n-CO2Me for example is strongly inﬂuenced by the value of n. For n = 0, 1, 2 or 3 the half wave potentials move from 0.72 V to 0.59 V, 0.49 V and 0.46 V (for n = 3).[78] A similar correlation was found for diferrocenyl compounds, that are bonded [78] by vinyl moieties. With increasing length of the polyvinyl chain (Fc(CH=CH)nFc), the

24 1.3 Ferrocene as Building Block potential diﬀerence between the two redox processes of the two iron centers in the cyclic voltammogram (∆E1/2) decreases. For n = 1, the diﬀerence amounts to 170 mV. For n = 3, this value decreases to ~100 mV. Compounds with more than three vinyl groups do not show two distinguishable processes anymore.[78]

In alkynyl bridged compounds of the general form Fc(C≡C)nFc (n = 1,2) redox processes generate relatively stable ferrocenium cations.[79] The more electron donating the conjugated bound substituents of the ferrocene moieties are, the better the corresponding ferrocenium cations are stabilized. Electron withdrawing groups on the other hand stabilize the neutral form of ferrocene and result in an anodic shift of the redox-wave in comparison to pure ferrocene.[71]

Figure 1.14: Cyclic voltammograms of ferrocenyl pyrazaboles a) - g) by Misra et al. as depicted in ﬁgure 1.13. Reaction conditions: dichloromethane, 0.1 m −1 [75] [NBu4][PF6], scan rate 100 mV s .

As already mentioned, Misra et al. synthesized and examined a group of ferrocenyl pyrazaboles via a Negishi type coupling reaction (figure 1.13 a)) and Sonogashira reactions (figure 1.13 b)-g)). Unfortunately, cylic voltammetry measurements were not carried out versus Fc/Fc+ but versus an Ag/AgCl electrode instead and can therefore not be compared to the aforementioned compounds in absolute numbers (see figure 1.14). Nevertheless, they nicely show the relative influence of different linker systems on the overall redox potential of the corresponding compounds.[75]

25 1 State of Knowledge

1.3.8 Ferrocene Substituted Scorpionate Ligands

As mentioned in chapter 1.1.1, tris(pyrazolyl)borate (Tp) ligands, so called scorpionates, have found a wide range of applications throughout inorganic chemistry. Therefore, it is not surprising, that it was attempted, to combine the aforementioned properties of ferrocene with those of the Tp ligand system. The ﬁrst approach in this direction was carried out by the father of scorpionate chemistry S. Trofimenko himself.[80] Trofimenko and coworkers started their experiments with the synthesis of a ferrocenyl substituted pyrazole. This precursors could be obtained from the reaction of acetylfer- rocene with ethyl formiate and hydrazine. From the resulting 3-ferrocenylpyrazole, it was possible to obtain the corresponding bis(pyrazolyl)borates.[80,81]

R N N B Pd(π - CH2CHCH2) R N N

Figure 1.15: First transition metal complex of a ferrocene substituted poly(1- [80] pyrazolyl)borate by Trofimenko and coworkers (R = C2H5).

From there, they could obtain ﬁrst transition metal complexes of the new ligands such as, for example, the palladium complex depicted in 1.15. These compounds were the ﬁrst poly(1-pyrazolyl)borate complexes, in which the boron backbone is bonded to a transition metal center via the nitrogen donors of the pyrazole rings and at the same time to another transition metal, in this case a ferrocenyl moiety, via one nitrogen atom and the carbon framework of a pyrazole ring.[81] However, it was not possible to prepare the corresponding tris(1-pyrazolyl)borates. The reaction conditions, that are required to synthesize the corresponding unsubstituted Tp ligand,[1] led in this case to decomposition of the ferrocenyl substituents.[80] Another approach was pursued by Jäkle et al. The ferrocenyl substituent of their ligands was not introduced at the pyrazole rings, but instead at the boron backbone of the ligand. Depending on the desired ligand, mono or di-substituted (dibromoboryl)ferrocenes were

26 1.3 Ferrocene as Building Block reacted with pyrazole and triethylamine, to obtain the corresponding ligand.[82] This technique on the one hand stabilized the boron nitrogen bond against hydrolysis. On the other hand, it was used as a linker for the potential use in a organometallic polymer, as depicted in figure 1.16. Following this procedure, a variety of different ligands and complexes could be synthesized. Among them were mono and dinuclear (see figure 1.16) as well as bisligand complexes and derivatives with higher sterical demand.[82,83]

N N B NN M N N N N Fe M N N B N N

Figure 1.16: Dinuclear complex [Fc(MBpz3)2] with ferrocene acting as linker group according to Jäkle et al. (M = Li, Tl).[82]

In 2010, Chen and Jordan reported on an altered Tp synthesis, which avoided the high temperatures, that were involved in the synthetic pathway of Trofimenko.[1] Instead, they performed a Lewis acid catalyzed synthesis at relatively low temperatures of only 60 ◦C.[84] However, ﬁrst tris(1-pyrazolyl)borates with ferrocene substituted pyrazole moieties were unknown before 2014. The Lewis acid catalyzed reaction by Chen and Jordan was adapted by Sirianni et al. to circumvent the heat induced decomposition of the ferrocenyl substituents. From this basis, they succeeded in the synthesis of the ﬁrst ferrocenyl- substituted hydrotris(pyrazolyl)borate ligands, as depicted in scheme 1.16.[85]

1. LiBH4, i MeB(O Pr)2 R R R (6 mol% vs pz) R B Toluene, 100 °C N N N 3 Fe 2. TlOAc HN N N N N Tl Fc R = H, Me, iPr Fe Fe

Scheme 1.16: Synthesis of TpFc,R ligands as thallium salts according to Sirianni et al.[85]

27 1 State of Knowledge

The group also investigated the electrochemical properties of the resulting compounds by cyclic voltammetry in dichloromethane with [NBu4][PF6] as electrolyte and Cp*2Fe as reference. In order the make the reported values more comparable to other measurements + 0 in this work, they were converted to potentials against Fc/Fc (Cp*2Fe, E = −0.59 V vs. Fc/Fc+).[86] The observed potentials were independent of the second substituents R of the pyrazole moieties (see scheme 1.16), which was surprising, since one of them contains electron withdrawing (CF3) and one of them electron donating (CH3) groups as second substituents. All three of them displayed a single reversible redox process at a half wave potential of approximately +30 mV vs Fc/Fc+ (compare 1.3.7).[85] The molecular structure of the methyl substituted derivative is depicted in ﬁgure 1.17. It shows the high sterical demand of the ligand, which is induced by the three ferrocenyl moieties, all of which are oriented towards the coordination site. This symmetrical isomer could be obtained from the crude mixture by thermal isomerization.[85]

Figure 1.17: Molecular structure of TpFc,MeTl as published by Sirianni et al.[85]

Another ferrocene substituted scorpionate ligand system was developed by Tampier et al. in 2013. They reported on the ﬁrst bis(pyrazol-1-yl)acetic acid bearing ferrocenyl substituents.[71] The synthesis of these new ligands started from ferrocene, which, after a transmetallation with zinc, was reacted in a Negishi coupling reaction, according to the procedure published by Mochida et al. (see 1.3.3).[64] After removal of the protecting trityl group, the already established one pot synthesis was used, to obtain the corresponding bis(pyrazol- 1-yl)acetic acid (Hbfcdmpza) (see scheme 1.17).[11,71]

28 1.3 Ferrocene as Building Block

R R R O R

N N N N N N N N Fe Fe Fe Fe R R R R R = H bfcpzm R = H bfcpzk R = CH3 bfcdmpzm R = CH3 bfcdmpzk

Scheme 1.17: Synthesis of bis(4-ferrocenyl-3,5-dimethylpyrazol-1-yl)acetic acid (H[bfcdmpza]) according to Tampier et al.[71]

While it was not possible to fully purify this ligand from educt contamination, the group could obtain a crystal structure of the corresponding iron(II) complex, which is depicted in ﬁgure 1.18.[71] Along with this compound, the group synthesized a variety of N,N coordinating derivatives. All of them could be suitable for future model complexes of Rieske dioxygenases, due to their beneﬁcial redox potential region, which reaches in to the redox potential region of Rieske ferredoxins with [2Fe-2S] clusters (see chapter 1.4).[71]

[71] Figure 1.18: Molecular structure of [Fe(bfcdmpza)2] by Tampier et al.

29 1 State of Knowledge

1.4 The Rieske Dioxygenase

The aforementioned Rieske clusters are electron reservoirs in enzymes like the Rieske dioxygenases and other oxygenases. These are iron based enzymes, capable of activating molecular oxygen and directly insert it into an organic cosubstrate, as was ﬁrst discovered by O. Hayaishi in 1955 as he was studying the catechol 1,2-dioxygenase.[87] Since then, mass spectrometry could show, that both atoms of oxygen, that are transferred during this cis-hydroxylation, derive from the same molecule of diatomic oxygen, as it is shown in scheme 1.18.[88]

H H H 18OH 16OH 18 16 + O2 + O2 or H 18 16 H OH H OH

Scheme 1.18: Example for the incorporation of molecular oxygen into organic substrates 16 in reactions catalyzed by Rieske dioxygenases, using a mixture of O2 18 [88,89] and O2.

Rieske dioxygenases in bacteria are mostly used for the aerobic decomposition of aromatic substances. However, using molecular oxygen as oxidizing agent for cis-hydroxy- lations is also an interesting option for synthetic chemistry. Oxygenases were used in this context, before they were even known to exist. In 1952, Peterson and Murray published the stereospecific steroid hydroxylation by fungi.[90] This revolutionized the synthesis of the anti-inflammatory cortisones by shortening the synthesis from 37 steps with 0.15 % overall yield to a six step synthesis. Subsequently, the price of progesterone dropped from US$ 200 to $ 6 per gram.[89] In modern synthetic chemistry, similar reactions are carried out by catalytical reactions with osmium tetroxide and hydrogen peroxide as oxidizing agents. The specific application of Rieske dioxygenases or synthetic analogues would however offer a probably cheaper and in any case more environmentally friendly alternative.[91] There are many Rieske dioxygenases with distinct structural and mechanistic properties to be found in nature. In general, they are enzymes of the family of the non-heme iron dioxygenases. The iron atom at the active site is coordinated by the aforementioned 2- His-1-carboxylate facial triade (see figure 1.2).[89,92] Depending on their substrates, they are divided into several groups, as for example naphthalene- or biphenyl-dioxygenases. Furthermore, Rieske dioxygenases are capable to perform a peroxide shunt instead of activating oxygen reductively. This is similar to what could be observed for cytochrome P450.[93,94] Exemplary, the focus will be on the naphthalene dioxygenase. It is a bacterial dioxygenase.

30 1.4 The Rieske Dioxygenase

Figure 1.19: Part of the protein structure of the naphthalene-1,2-dioxygenase (NDOS, PDB:1NDO) with the Rieske [2Fe-2S] cluster connected via [89,92,93] Asp205.

In contrast to plant-type iron-sulfur clusters, where the iron-sulfur clusters are coordinated by four cysteine ligands, they are bound by two histidine and two cysteine donors.[95] The structure of the active site of the napthalene-1,2-dioxygenase (NDOS, PDB:1NDO) is depicted in the ﬁgures 1.19 and 1.20.[89,92,93] The active site of the naphthalene-1,2-dioxygenase contains a 2-Histidine-1-carboxylate motif, to which an iron(II) center is bound. Molecular oxygen is activated at this site and the respective substrate, in this case naphthalene, is oxidized. The iron center is thereby bonded by the two nitrogen donors of the two histidine moieties and by the carboxylate group of a aspartic acid in a κ2-O,O fashion.[89,92]

HisN S Cys OH2 3+ 3+ O NHis Fe Fe Fe2+ ~ 3.0 Å ~ 2.7 Å N S Cys O N NH HN O O

Asp205

Figure 1.20: Schematic representation of the naphthalene-1,2-dioxygenase with the [89,92,93] Rieske [2Fe-2S] cluster connected over Asp205.

Another aspartic acid (Asp205) serves as bridge to a Rieske [2Fe-2S] ferredoxine cluster. The iron(II) center is oxidized to iron(III) during the catalytic cycle. The restoration

31 1 State of Knowledge

S S 1 e- Fe2+ Fe3+ Fe3+ Fe2+ Fe2+ Fe3+

S S

+ O2

Fe3+ Fe3+ Fe3+

+ H OH OH H

Scheme 1.19: Reaction cycle of naphthalene dioxygenase according to Wackett et al.[89] of the initial iron(II) species is carried out with electrons from the Rieske cluster. The electrons are thereby transferred over the bridging aspartic acid (Asp205). The electron reservoir is then reﬁlled with electrons from NADH. Thus electrons are transported from NADH over the [2Fe-2S] cluster to the active site and thereby to the molecular oxygen. This transfer chain spreads over 12 Å and is crucial for the catalytic activity.[89,92]

OH 3+ + OH A Fe OH O2 O Fe2+ Fe3+ B O OH Fe5+ Fe3+ + OH OH

Scheme 1.20: Possible reaction pathways with intermediates of the dioxygenation by Rieske dioxygenases.[89]

The reaction cycle depicted in scheme 1.19 was deduced from single turnover experiments. In this cycle, the histidine bonded iron center of the Rieske cluster and the previously formed iron(III) center of the active site are reduced to iron(II). The next step is the

32 1.4 The Rieske Dioxygenase concerted oxidization of the substrate, as depicted in scheme 1.20. The electrons for the oxidization are delivered one by the iron(II) center of the active site and one by the Rieske cluster.[96] The redox potential of the Rieske cluster varies greatly, depending on the electrostatic environment in the enzyme. The potential ranges from −150 mV to +400 mV against SHE.[97,98]

1.4.1 Model Complexes of the Rieske Dioxygenase

Model systems for the Rieske dioxygenase are sparse. There are several model complexes of the [2Fe-2S] cluster by Meyer and coworkers.[99–101] One example of them is depicted in ﬁgure 1.21. These clusters show a highly tunable reduction potential, depending on the substituents R. The half wave potentials range from −1.47 V (R = Cl) over −1.56 V (R = H) to −1.94 V (R = tBu) vs Fc/Fc+.[100] However, these complexes can hardly be used in a working model of a Rieske dioxygenase, because the iron centers of the cluster can not be bonded to an additional active site, since they are coordinatively saturated.

R R R R S S S (NEt4)2 Fe Fe S S S

R R R R

Figure 1.21: [2Fe-2S] clusters according to Ballmann et al. (R = Cl, H, tBu).[100]

Therefore, functional models are of interest. Iron(II) complexes of the ligands chlorido-3- (dipyridin-2-yl-methyl)-1,5,7-trimethyl-2,4-dioxo-3-azabi-cyclo[3.3.1]nonan-7-carboxylato- iron(II) and bis(di-(2-pyridyl)methyl)benzamid-iron(II) depicted in ﬁgure 1.22 work as such, while not being structural models of Rieske dioxygenases.[102,103]

O OH H N N N N O O N N O

Figure 1.22: Ligands for Rieske dioxygenase models by Oldenburg et al.[102,103]

33 1 State of Knowledge

These models however have redox potentials between −2.0 V and −1.5 V vs Fc/Fc+.[102,103] Thus they are in the same range as the [2Fe-2S] cluster models reported by Ballmann et al.[100] These values are drastically cathodically shifted in comparison to the natural Rieske ferredoxine clusters, which means, they are stronger reducing agents. A new approach was hence started by Burzlaff and coworkers. Ferrocene, with a reduction potential of +400 mV versus SHE (see chapter 1.3),[76] offers the opportunity, to create model systems, that reach into the redox potential of natural Rieske clusters of −150 mV to +400 mV against SHE.[97] As shown before, the electrochemical potential of ferrocene can be influence by its chemical environment. Furthermore, the Rieske dioxygenases contain the 2-Histidine-1-carboxylate facial triade motif at their active sites, which can be resembled by the bdmpza ligand (see chapter 1.1.2). The group attempted to combine these two concepts by substituting the pyrazole rings of the established ligand with ferrocenyl moieties, which should serve as electron reservoirs, as it is shown in figure 1.23.[71]

N N O O N N Fe e-

Figure 1.23: Possible electron transfer in a ferrocene based bis(pyrazolyl)acetate model system.[71]

The synthesis of the resulting 4-ferrocenyl substituted bdmpza derivative and the resulting crystal structure of the corresponding iron(II) complex was already shown in chapter 1.3.8. While this compound could not be studied by cyclovoltammetry due to educt contaminations, the carbonyl and methylene bridged derivatives were analyzed.[71] The methylene bridged ligand bis(4-ferrocenyl-3,5-dimethylpyrazol-1-yl)methane (bfcdmpzm) could easily be obtained by the reaction of the corresponding 4-ferrocenylpyrazole in a base assisted substitution reaction on dichloromethane under phase transfer conditions (see 1.21 top).[71] The carbonyl bridged derivate bis(4-ferrocenyl-3,5-dimethylpyrazol-1-yl)ketone (bfcdmpzk) was accessible from the reaction of aforementioned pyrazoles with triphosgene in the presence of triethylamine. (see 1.21 bottom).[71] The cyclic voltammograms of these two compounds revealed each one reversible redox potential. The half wave potentials versus Fc/Fc+ were determined to −9 mV for bfcdmpzm and −12 mV for bfcdmpzk (at a scanrate of 0.3 V/s).[71]

34 1.4 The Rieske Dioxygenase

N N KOH, K2CO3, CH Cl N N 2 2, Fe Fe TEBAC

NH N Fe O NEt3, triphosgene N N N N Fe Fe

Scheme 1.21: Synthesis of bis(4-ferrocenyl-3,5-dimethylpyrazol-1-yl)methane (bfcdmpzm) and bis(4-ferrocenyl-3,5-dimethylpyrazol-1-yl)ketone (bfcdmpzk) according to Tampier et al.[71]

These values are very promising, since the redox potentials reach into the range of natural Rieske clusters.[97] Especially in combination with a N,N,O binding motif, such compounds could serve as interesting model systems for Rieske dioxygenases.[71] There- fore, new ligands based on a similar concept will be presented as part of this work (see chapter 3.4).

35 1 State of Knowledge

1.5 Molybdenum Containing Enzymes

Apart from the iron depending metalloproteins, another group of enzymes are of interest for this work, this is the group of molybdenum containing enzymes. Molybdenum can be found in multinuclear metal centers of nitrogenases and is therefore crucial in the nitrogen ﬁxation.[104,105] Moreover, they are also common metal centers in the active sites of mononuclear metalloproteins. Such proteins usually catalyze oxygen-atom-transfer (OAT) reactions and are therefore called oxotransferases, although this name has no intended mechanistical connotation.[106,107] The common structural feature of most of these enzymes is an active site based on a Mo=O unit. Hence they are referred to as oxomolybdenum enzymes.[108]

Figure 1.24: Crystal structure of the chicken sulﬁte oxidase.[109] (PDB:1SOX)

This large family of metalloproteins can be divided in three groups by their reaction mechanisms. Enzymes of the ﬁrst group are hydroxylases, which are able to catalyze the oxidative hydroxylation of a broad range of aldehydes and aromatic heterocycles under cleavage of a C-H bond. This group is called xanthine oxidase family.[106] The

36 1.5 Molybdenum Containing Enzymes two remaining groups both catalyze proper OAT reactions. One of them is the sulﬁte oxidase family, a member of which is depicted in ﬁgure 1.24. The other one is the family of DMSO reductases. These two families can be distinguished by their characteristic UV/vis spectra.[106]

1.5.1 The Sulﬁte Oxidase

Molybdenum containing metalloproteins are important for the human biochemistry, as well. Xanthine oxidase, aldehyde oxidoreductase and sulfite oxidase (SO) can be found in the human body.[110] If the latter is not functional due to a genetic disorder, a disease called molybdenum cofactor deficiency (MoCD) is caused. In the human body, the SO catalyzes the oxidation from sulfite to sulphate, whereat electrons are transferred to ferricytochrome c (cyt c, see figure 1.25).[106,111,112] If this detoxification step is disabled, the high physiological concentration of sulfite leads to severe symptoms like the dislocation of ocular lenses, mental retardation and attenuated growth of the brain.[113]

2− 2− + SO3 + H2O + 2 (cyt c)ox → SO4 + 2 (cyt c)red + 2 H

Figure 1.25: Reaction equation of the sulﬁte oxidase.[106,111,112]

Worldwide, there are only about 100 known cases of this disease.[114] It can be caused by two different genetic disorders, which both lead to the inability to produce the necessary molybdenum-cofactor (Mo-co) of the enzyme. This cofactor is common among the oxomolybdenum enzymes. It is depicted in figure 1.26. In two thirds of the cases, patients suffer from the inability to form a precursor of Mo-co (MoCD type A), which is called cyclic pyranopterin monophosphate (cPMP).[114,115] In the remaining patients, the disease is caused by a point mutation in the protein itself, which is called an isolated sulfite oxidase deficiency, since only the SO itself is affected (MoCD type B).[115–117] Until today, there is no known cure for this disease, which usually leads to death in early infancy.[118] Despite of this, a case in 2009 caused a sensation. An infant girl with early symptoms of MoCD was treated with cPMP, which was experimentally expressed in cultures of Escherichia coli. by Veldmann et al., who were studying the influence of cPMP supplementation on mice.[118,119] As a result of this treatment, the little girl fully recovered. The crystal structure of this important human enzyme is still unknown, only the structure of the heme domain was reported so far.[120] The only known crystal structure of an intact animal SO was obtained from the chicken liver enzyme and is depicted in figures 1.24 and 1.26.[109] Figure 1.24 shows the tertiary structure of the enzyme. It is a homodimer, whose

37 1 State of Knowledge subunits consist of a heme domain the N -terminus and the Mo-co at the larger C-terminal domain. The two domains are connected over a flexible polypeptide.[109] The active site of the protein, which is depicted in figure 1.26, contains a molybdenum atom, which is coordinated in a pseudo square pyramidal geometry by five ligands. The axial position is occupied by the terminal oxo group. The equatorial positions contain three sulfur atoms, two from the Mo-co, one from a cysteine moiety. The remaining free coordination site is occupied by a water/hydroxo ligand.[110]

Figure 1.26: Active site with molybdenum-cofactor of the chicken sulﬁte oxidase.[109] (PDB:1SOX)

The mechanism of action of the sulfite oxidase was proposed by Hille and is generally accepted by now. It is split in an oxidative and a reductive half reaction.[121–124] In the oxidative half reaction, the metal center is oxidized by cyt c, as already mentioned (see figure 1.25). This process is divided in two steps, in each of which one intraprotein electron transfer from molybdenum to the cyt c takes place. The actual oxidation of the substrate sulfite happens during the reductive half reaction (see scheme 1.22). Hille proposed an attack of the free electron pair of the sulfite at one of the Mo=O units of the molybdenum center.[122]

38 1.5 Molybdenum Containing Enzymes

O S Scys O Mo O H O O S O S 2 O (IV) H O S O O O O S O O O S Scys S Scys Mo Mo S (VI) O S (IV) OH2

O S Scys e-, nH+ Mo e- S (V) OHn

Detectable by EPR

Scheme 1.22: Proposed reaction mechanism of the sulﬁte oxidase by Hille et al.[108,110]

The proposed mechanism was supported by EPR spectroscopy, which was able to detect the intermediate molybdenum(V) species. It was deduced from model reactions of molybdenum(VI) dioxo compounds with phosphines.[125,126]

Me SO Ph3PO 2

MoO(L-NS2)(DMF)

DMF DMF

MoO(L-NS2)(OPPh3) MoO(L-NS2)(Me2SO)

MoO2(L-NS2) PPh3 Me2S

Scheme 1.23: Catalytic cycle for the reduction of DMSO catalyzed by MoO(L-NS2) with [127] PPh3 as reductant.

These model reactions were carried out with an model complex for oxo molybdenum enzymes, which was developed by Holm and coworkers in 1985 and contained a 2,6-bis(2,2- [125,128] diphenyl-2-mercaptoethanyl)pyridine ligand (L-NS2). This bulky ligand was necessary to prevent the formation of oxo-bridged molybdenum(V) dimers.[125] The corresponding molybdenum(VI) complexes performed successfully at the quantitative reduction of [125,128] (p-C6H4F)2SO and 3-ﬂuoropyridine N -oxide. Furthermore, this system was able to catalyze the oxidation of phosphine substrates.[127]

39 1 State of Knowledge

The catalytic cycle is depicted in scheme 1.23. Therein, oxygen was transferred from dimethyl sulfoxide to a phosphine substrate under the release of dimethyl sulﬁde. The system proved to be a good functional model of oxo-transferase enzymes, with a high stability with turnover numbers above 500 before decomposition.[127] Another model system was developed by Heinze and Fischer. In order to overcome the tendency of oxo molybdenum complexes to form molybdenum(V) dimers, they used a copolymerized ligand system composed of two 2-imino-pyrrolato ligands, which formed a bis(chelate) dioxido molybdenum(VI) complex as shown in ﬁgure 1.27.[129] The formation of such oxo-bridged dinuclear molybedenum(V) species was found to be a thermodynamic sink in this system via density functional theory computations.[130]

iPr iPr S O O S iPr iPr

N N N Mo N O O

Figure 1.27: Polymerized model system by Heinze and Fischer.[129]

This two-point fixation resembles the fixation of the molybdenum center in real oxotransferases like the sulfite oxidase or DMSO reductase, which is therein accomplished by pterin dithiolene and cysteinato ligands (compare figure 1.26).[106,129,131–134] In their study, Heinze and Fischer catalyzed the oxidation of trimethylphosphine. The required oxygen atoms for the OAT were taken from water molecules. The protons of these t [135] water molecules were transferred to the phosphazane base P1- Bu. The anionic molybdenum species, which is formed by this process is then reduced by [Fe(AcC5H4)2][BF4] to restore the initial catalyst.[129] In order to find a way to catalyze this reaction under homogeneous conditions, Heinze et al. studied a similar, yet not solid phase fixated system, concerning its electrochemical properties. However, they found that it is impossible to suppress condensation and com- proportionation of the system without an excess of reactive substrate and the absence of water. Therefore, a full biomimetic catalytic cycle is not possible under homogeneous conditions with this system.[136] However, recent studies of the group have shown, that ligand derivatives with a drastically increased sterical demand, which was achieved by the introduction of isopropyl groups, could possibly avoid the formation of dimeric complexes.[137]

40 1.5 Molybdenum Containing Enzymes

1.5.2 The DMSO Reductase

The second group of oxygen-atom-transfer catalyzing oxomolybdenum enzymes consists of the DMSO reductases (see chapter 1.5).[106] These enzymes are found exclusively in eubacteria, such as E. coli [138], R. sphaeroides [139] and R. capsulatus [140]. They serve as reductases under aerobic conditions and allow for an higher energy yield than fermentation could deliver.[141] Fermentation is the least eﬀective process to obtain energy, since it is only yielded by substrate chain phosphorylation.[138]

Figure 1.28: Crystal structure of dimethyl sulfoxide reductase from Rhodobacter capsulatus.[142] (PDB:1DMS)

While catalyzing the same reactions, the protein structures differ significantly among these different bacteria. The proteins found in R. sphaeroides and R. capsulatus (see figures 1.28 and 1.29) contain the Mo-co (see figure 1.30) as only cofactor. The corresponding E. coli enzyme on the other hand consists of three subunits: the A-subunit contains the Mo- co, a B-subunit with four [4Fe-4S] clusters and a transmembrane C-subunit. The latter is also responsible for the binding and oxidation of menaquinol. In this process, electrons are transferred from the C-subunit to the B-subunit and from there to the Mo-co.[141] Figure 1.29 shows the active site of the DMSO reductase of R. capsulatus.[142] As can be

41 1 State of Knowledge seen, the molybdenum center is located between two molybdopterin units, which form the molybdenum cofactors. This common feature of the diﬀerent enzymes is depicted in ﬁgure 1.30 for comparison.[141]

Figure 1.29: Structure of the active site of the dimethyl sulfoxide reductase from Rhodobacter capsulatus.[142] (PDB:1DMS)

So far, only two crystal structures of DMSO reductases could be obtained. On the one hand the crystal structure of the DMSO reductase of R. capsulatus [142,143], which is depicted in ﬁgure 1.28 and on the other hand the X-ray structure of the DMSO reductase of R. sphaeroides.[144]

O O O S Mo O H N S HN 2- OPO3 H2N N N O H

Figure 1.30: Structure of the common molybdenum-cofactor.[141]

A reaction mechanism for the DMSO reductase was proposed by Kisker et al. in 1997 (see scheme 1.24).[144–146] As can be seen in the crystal structure of the DMSO reductase (ﬁgure 1.29), the molybdenum center is bound by two pterin derivatives. The reaction itself can be divided in two half reactions, as it was already observed for the SO (compare chapter 1.5.1). In the oxidative half cycle, the reduced molybdenum(IV) species of the enzyme binds the substrate DMSO. The bonding weakens the sulfur oxygen bond and two electrons are transferred from the molybdenum center to the substrate. Dimethyl sulﬁde (DMS) is released and the molybdenum center remains in an oxidation state of VI.[144–146]

42 1.5 Molybdenum Containing Enzymes

O-ser IV S Mo S S S OH- DMSO

SMe2 ser-O OH ser-O O V S IV Mo S S Mo S S S S S

+ H+ - H+ DMS 2

ser-O O ser-O O V VI S Mo S S Mo S S S S S e-

Scheme 1.24: Proposed reaction mechanism of the DMSO reductase. Coordination in the Mo(IV) and Mo(V) states as observed in the crystal structures of these forms.[144–146]

In the reductive part of the reaction, a proton and two electrons are transferred to the metal center. A hydroxyl anion is released and the initial molybdenum(IV) species is restored. The electron source for this reaction is most likely a water soluble cytochrome.[109,144–146]

43 1 State of Knowledge

1.5.3 Model Complexes of the DMSO Reductase

In order to mimic the pterin coordination environment of the Mo-co in the DMSO reductase, Fischer et al. studied a trichloro(quinonoid-N(8)H -6,7-dihydropterin)oxomolybde- + [147] num(IV) (Mo(IV)OCl3(H -q-H2Ptr)), which is depicted in ﬁgure 1.25.

Cl Cl Cl O O O Cl Mo Cl Cl Mo Cl Cl Mo Cl O O O N N N HN HN HN

H2N N N H2N N N H2N N N H H H Scheme 1.25: Structure of trichloro(quinonoid-N(8)H-6,7-dihydropterin)oxomolybdenum(IV) as determined by Fischer et al. via X-ray structure analysis.[147]

The reaction of this complex with DMSO was monitored via 13C NMR spectroscopy and mass spectrometry. The authors postulated a change of the oxidation state of the molybdenum center from the chemical shift of the carbonyl carbon atom of the pterin unit. The formation of a not closer speciﬁed Mo(VI)(O)2 species was assumed. During this reaction, a release of DMS was observed via mass spectrometry.[147] While the system was able to transfer oxygen from DMSO to the molybdenum center, the reaction was not carried out catalytically, since the pterin ligand was presumably oxidized in a second reaction step. Thus the original complex could only be restored by the addition of new tetrahydropterin to the reaction mixture.[147]

t Bu tBu O O tBu 1:1 1:2 O N Mo N N toluene toluene Mo O [MoO2Cl2] + pzK N N N Cl tBu tBu tBu

Scheme 1.26: Synthesis and structure of DMSO reductase model complexes by Most et al.[148]

Therefore, Most et al. found a new approach. They employed µ2-pyrazolato ligands with sterical demanding tBu moieties.[148] The bulky ligands were supposed to avoid bridging structures of molybdenum complexes with pyrazolato ligands.[149] Depending on the stoichiometry, either 1:1 or 1:2 complexes of molybdenum(VI) dichloride dioxide with potassium 3,5-di-tert-butylpyrazolate (pzK) could be prepared, as depicted

44 1.5 Molybdenum Containing Enzymes

[148] 2 2 in scheme 1.26. The resulting compounds [MoO2Cl(µ -pz)] and [MoO2(µ -pz)2] showed catalytic activity similar to DMSO reductases in the presence of triphenylphosphine and DMSO:[148]

[Mo] PPh3 + (Me)2SO −−→ OPPh3 + (Me)2S

31 The experiments were carried out in deoxygenated DMSO-d6 and analyzed via P NMR spectroscopy. The model compounds were applied in a concentration of 10 mol%. While the 1:1 complex was able to oxidize 100 % of the triphenylphosphine within two hours at room temperature, the 1:2 complex did not exhibit any activity under these conditions. Yet, at a temperature of 80 ◦C, it reached similar activity as the 1:1 complex. The formation of DMS could be veriﬁed via gas chromatography.[148] Inspired by these results, Mösch-Zanetti and coworkers developed a wide range of molybdenum and tungsten containing catalyst in order to investigate the mechanism and geometry dependent activity regarding OAT reactions.[107,150] The same reaction was examined in the studies of Hammes et al. The group used dioxo-molybdenum complexes of scorpionate ligands such as bis(3,5-dimethylpyrazol-1- yl)acetate (bdmpza, see also 1.1.2). The kinetics regarding the oxidation of triphenylphosphine has been studied for several scorpionate complexes.[151] The formation of µ-oxo bridged bdmpza oxo-molybdenum complexes was reported by Ceh˘ and coworkers, which is, as outlined above, unfavorable for OAT reactions.[152–154] Therefore, a copolymerizable derivative was developed as part of this work (see chapter 3.1).

45 1 State of Knowledge

1.6 Coordination Polymers

1.6.1 Building Blocks for Coordination Polymers

In general, polymers are deﬁned as high molecular weight molecules, which consist of repeated monomeric units, linked with covalent bonds.[155] Coordination polymers on the other hand are inﬁnite systems of alternating metal ions and organic ligands, linked via coordination or other weak chemical bonds.[156] If such systems build higher dimensional order structures, they are also referred to metal-organic coordination networks or metal- organic frameworks (MOF).[157]

neutral ligands N N

N H O N N

N NN N O

N N anionic ligands

O O O O O O

O O O O O O O O

cationic ligands N N N N

N N N N NN Figure 1.31: Selection of typical used organic molecules as organic linkers in coordination polymers.[158]

46 1.6 Coordination Polymers

To be considered as such, the ligand must be a bridging organic group. At least in one dimension, the metal ions must solely be bridged by this organic ligand. Furthermore, there must be at least one carbon atom between the donor atoms of the ligand.[157] A selection of common organic linkers for coordination polymers is depicted in ﬁgure 1.31.[158] As can be seen, neutral ligands and cationic ligands mostly rely on nitrogen heterocycles, while anionic ligands often use carboxylate donors.

linear chain

ladder zigzag chain

Figure 1.32: Various common 1D, 2D and 3D polymer motifs.[158]

Depending on the number and geometry of the donor functions of the ligand, a vast variety of diﬀerent structural motifs can be obtained (see ﬁgure 1.32).[158,159] Even 1D coordination polymers are known to form unique higher dimensional packing motifs due to π − π and other intermolecular interactions.[160] For this work, two groups of ligands for coordination polymers are of special interest: the polyyne bridged ligands and coordination polymer ligands based on pyrazole moieties.

47 1 State of Knowledge

1.6.2 Polyyne Bridged Coordination Polymers

In the recent years, several groups examined coordination polymers of polyyne bridged lig- and systems.[161–170] Schröder and coworkers used among others silver complexes of [1,4- bis(4-pyridyl)butadiyne] (pybut)[171] and [1,4-bis(4-pyridylethynyl)phenylene] (pyphe)[172] to study the resulting interactions between the polymer chains.[161]

Figure 1.33: Arrangement of inﬁnite chains in {[Ag(pybut)]BF4 × MeCN}∞ (top) and [161] {[Ag(pybut)PO2F2 × MeCN}∞ (bottom).

The arrangements of infinite chains depicted in figure 1.33 strongly depended on the influence of the counter ion. Stronger coordinating anions stabilize short cation - cation distances and the formation of head-to-head ligand placement (see figure 1.33, bottom). Weakly coordinating anions on the other hand promote a different chain arrangement with the ligands in a head-to-tail orientation and cationic centers separated by over 7 Å (see figure 1.33, top).[161] In order to create non linear 1D coordination polymers with non linear polymer chains, ligands with angular donor functions are required. Burzlaff and coworkers recently reported on a butadiyne bridged ligand, bearing imidazole moieties. This bis(N -methylimidazol-2-yl)butadiyne (bmib) ligand was synthesized in a Glaser homo coupling reaction from 2-ethynyl-N -methylimidazole.[170]

N N

Figure 1.34: Structure of bis(N-methylimidazol-2-yl)butadiyne (bmib) according to Burzlaff and coworkers.[170]

The reaction of this ligand with zinc(II) acetate yielded a 1D coordination polymer. The structure revealed by X-ray structure analysis consisted of alternating dinuclear

48 1.6 Coordination Polymers

[Zn2(O2CCH3)4] paddle-wheel units and trinuclear [Zn3(O2CCH3)6] units, as depicted in ﬁgure 1.35.[170]

Figure 1.35: Crystal structure of the coordination polymer [Zn5(OAc)10(bmib)2]n according to Burzlaff and coworkers.[170]

The shape of this structure reminded of the battlements of medieval castles and was therefore named after it. This alternating paddle-wheel and trinuclear coordination with N,N donor ligands is very rare and has only been reported once before.[170,173]

49 1 State of Knowledge

1.6.3 Pyrazole Based Ligands for Coordination Polymers

While most of the nitrogen donor based ligands for coordination polymers rely on pyridine moieties (see chapter 1.6.1), pyrazole based systems gained more and more attention in the recent years.[174–179]

N NH X = H, NO2, NH2, N NH HN N OH, SO3H HN N X (i) (ii)

O HN N NH N HN N OH (iii) (iv)

H H N N N N

(v) (v) N N N N H H Figure 1.36: Selection of known pyrazole based ligands for coordination polymers. (i)[175], (ii)[176], (iii)[177], (iv)[178], (v)[179].

Such ligands were employed by Colombo et al. for the synethesis of isoreticular families of cobalt and nickel MOFs bearing organic functionalities (see figure 1.36 (i)). The introduction of different groups X at the bridging aryl ring enabled the group to fine tune pore size, shape, volume and hence the adsorption capacity and selectivity toward specific guest molecules. By this procedure they were able to achieve a high adsorption sensitivitiy in gas separation experiments of mixtures of polar and apolar gases.[175] A similar structure was developed by Heering et al. with cobalt coordination polymers of ligand (iii) (figure 1.36). They also obtained isoreticular structures, which showed promising results at low-pressure hydrogen storage and the absorption of carbon dioxide.[177] Silver(I) sulfate coordination polymers of the bipyrazole ligand (ii) in figure 1.6.1 exposed a high degree of structural diversity depending on both solvent and temperature during the crystallization process.[176]

50 1.6 Coordination Polymers

N NH + Ag2SO4 HN N

120 °C, H2O/EtOH 90 °C 120 °C, H2O/MeCN H2O/MeCN

Scheme 1.27: Crystal structures resulting from the reaction of bispyrazole with silver(I) sulfate at diﬀerent conditions according to Du et al.[176]

The resulting structures are depicted in scheme 1.27. While a reaction temperature of 120 ◦C in ethanol led to the formation of a 2-fold 3D net (scheme 1.27, left), the same reaction in acetonitrile resulted in the formation of a 3D polycatenation with interpene- trating planes (scheme 1.27, right). If the temperature was lowered to 90 ◦C during the reaction in acetonitrile, helix based 2D layers were obtained (scheme 1.27, middle).[176] Du et al. found one reason for this coordination behavior in the two different possible confirmations of the bispyrazole ligand. The metal centers can either be coordinated in a trans or cis fashion to the ligand. While the helical structure consists of purely trans coordinated silver ions, the other two structures consist of different mixtures of cis and trans conformations.[176]

O R R

O N N N N O

R R O R = H / CH3

Figure 1.37: Structures of 1,4-bis[1-Boc-pyrazol-4-yl]butadiyne and 1,4-bis[1-Boc-3,5- [180–182] dimethylpyrazol-4-yl]butadiyne (Boc2L).

During the course of this thesis, Navarro and coworkers picked up a concept of Vasilevsky et al. for the synthesis of 1,4-bis[1-(1-ethoxyethyl)pyrazol-4-yl]butadiyne.[183] Based on

51 1 State of Knowledge this protocol, it was possible to synthesize ﬁrst metal organic frameworks based on this [180–182] ligand as well as the 3,5-dimethyl substituted derivative (Boc2L) (see ﬁgure 1.37). Starting from these compounds they could obtain crystal structures of metal organic frameworks containing nickel and cobalt. The tert-butyloxycarbonyl (Boc) protecting group was removed in situ during the reaction with the metal salts. Therefore, the structures contain anionic pyrazolate species, allowing a κ2 N,N coordination. The molecular structure of the respective cobalt(II) oxide MOF is depicted below.[181]

Figure 1.38: Perspective view, down [001], of the doubly interpenetrated networks found in the crystal structure of Co4O(L)3. The two symmetry-related frameworks are depicted in blue and yellow for the sake of clarity.[181]

As can be seen in ﬁgure 1.38, the structure of Co4O(L)3 consists of a two-fold interpene- 6− trated MOF, containing tetrahedraly coordininated Co4O centers. Similar to this, one task of this work will be to isolate unprotected 1,4-bis(1H -pyrazol- 4-yl)butadiyne ligands suitable for the formation of coordination polymers and to obtain respective linear coordination polymers of the free ligand. (see chapter 3.3).

52 2 Objectives and Aims

53 2 Objectives and Aims

During the last years, Burzlaff et al. investigated the synthesis and coordination behavior of heteroscorpionate ligands. In the beginning, bis(pyrazol-1-yl)acetic acids were used and modified concerning their sterical demand in order to influence their coordination behavior. This was achieved by the introduction of bulkier substituents in the positions 3 and 5 of the pyrazole rings.[11,12] The concept was later on extended to bis(pyrazol-1-yl)methane ligands, as was shown in chapter 1.1.3.[22–26] However, all of these concepts disregarded the possibility to introduce functional groups in position 4 of the pyrazole rings. First attempts in this direction were carried out by Türkoglu et al. in 2010, when they introduced vinyl groups at this position to obtain ligands capable of solid phase fixation via vinylogous polymerization reactions (see chapter 1.2.4).[35] The first part of this thesis should be a first catalytic study of polymeric materials derived from this ligand. Their reactivities should be evaluated in the context of a model system for the DMSO reductase. The transfer of oxygen from dimethyl sulfoxide to triphenylphosphine should be used as model OAT reaction. Therefore, N,N and N,N,O coordinated dioxomolybdenum complexes of the corresponding ligands were to be synthesized and polymerized. The influence of the polymerization process on the coordination motif as well as the influence of the polymerization on the ability of the resulting lig- and charged material to coordinate metal fragments was to be investigated. The amount of molybdenum incorporation in the respective polymers should be analyzed via atomic absorption spectroscopy (AAS). Finally, the influence of the solid phase fixation of the catalytic species on their catalytic performance concerning the aforementioned OAT reaction should be determined. Apart from vinyl substituted pyrazole ligands, ethynyl substituted pyrazole based ligands should be developed. To do so, 4-ethynyl substituted pyrazoles were to be synthesized, which should then be used in the synthesis of bis(pyrazol-1-yl)acetic acid and bis(pyrazol- 1-yl)methane derivatives. Such substituents could then serve as versatile linker groups in order to add additional functionalities to the resulting ligands. The corresponding one pot syntheses using dibromoacetic acid and phase transfer conditions to obtain the bis(pyrazol-1-yl)acetic acid derivative and thionyl chloride followed by pyridine and an aldehyde to obtain bis(pyrazol-1-yl)methane derivatives as established by Burzlaff et al.[11,23] should be used as a synthetic route towards such ligand systems. Starting from 4-ethynyl pyrazoles, bisacetylene bridged ligands suitable for coordination polymers should be synthesized via Glaser type coupling reactions. In order to avoid premature formation of such polymers during the metal catalyzed coupling reactions, bulky protecting groups should be applied. The ability of the resulting ligand to form 1D coordination polymers with metal fragments should be verified via X-ray structure determination of the resulting materials. Such compounds could prove useful in the field

54 of molecular electronics. The last part of this work should be the investigation of possible model systems for Rieske dioxygenases based on bis(4-ethynylpyrazol-1-yl)acetic acid derivatives bearing ferrocenyl moieties (see chapter 1.4). The acetylene function of the ligand precursors should therein serve as a linker group for Click reactions with ferrocenyl azides. For Sonogashira type coupling reactions, the corresponding 4-iodopyrazole derivatives should be synthesized. The electrochemical potential of the ferrocenyl moieties in these compounds should be inﬂuenced by changes in the chemical environment of the ferrocenyl groups. Therefore, the half wave potentials of the resulting model compounds should be determined and optimized.

55 56 3 Results and Discussion

57 3 Results and Discussion

3.1 Oxo-Transfer Catalysis by Chelate and Scorpionate Oxomolybdenum Complexes

In the ﬁrst part of this thesis, model-systems for DMSO reductases was to be synthesized starting from the above mentioned bis(3,5-dimethyl-4-vinylpyrazol-1-yl)acetic acid (Hbdmvpza) ligand (see chapter 1.2.4) as well as the N,N coordinating bis(3,5-dimethyl- 4-vinylpyrazol-1-yl)methane (bdmvpzm).[35]

O OH

N N N N N N N N

Figure 3.1: Polymerizable ligands for the application in DMSO reductase models.

In order to do so, these ligands were to be prepared from 3,5-dimethylpyrazole and had to be reacted to the corresponding oxomolybdenum complexes. The same should be done with the respective copolymers of these ligands. Such compounds should be capable of performing OAT reactions in a similar way, as natural DMSO reductases do. Thus, such compounds could serve as model systems to study the reactivity and mechanism of action of these enzymes. Furthermore, they should serve as a benchmark for the inﬂuence of the polymer matrix on the catalytic activity of the resulting materials.

O O O O O O MMA EGDMA

Figure 3.2: Monomers for the copolymerization of bdmvpzm (2) and Hbdmvpza (3), (left: MMA, right: EGDMA).

The co-monomers that should be used for these polymer embedded model systems are depicted in ﬁgure 3.2. On the one hand methyl methacrylate (MMA) and on the other hand ethylene glycol dimethacrylate (EGDMA) were used. While the former leads to linear polymer strains, the latter is a crosslinker due to its two polymerization sites. This property should lead to three dimensional networks with distinct diﬀerent properties.

58 3.1 Oxo-Transfer Catalysis by Chelate and Scorpionate Oxomolybdenum Complexes

3.1.1 Bis(3,5-dimethyl-4-formylpyrazol-1-yl)methane (1)[44]

The ﬁrst step towards a copolymerizable 4-vinyl substituted ligand starts from bis(3,5- dimethylpyrazol-1-yl)methane, which can be easily obtained in a phase transfer reaction of 3,5-dimethylpyrazole in dichloromethane under basic conditions, as shown by Juliá et al.[43] Starting from there, a Vilsmeier-Haack formylation was carried out, which led to the formation of the corresponding bisaldehyde derivative. The Vilsmeier reagent was hereby prepared by the reaction of phosphorous oxychloride with dimethylformamide at a temperature of 96 ◦C. The latter served as the solvent at the same time. After aqueous workup, the desired product is obtained in yields of 26 % referring to bis(3,5- dimethylpyrazol-1-yl)methane.

O O N N 1. POCl3, DMF N N N N 2. H2O N N

Scheme 3.1: Synthesis of bis(3,5-dimethyl-4-formylpyrazol-1-yl)methane (1).[44]

The 1H NMR spectrum of compound 1 reveals the two methyl groups in position 5 of the pyrazole with a chemical shift of 2.18 ppm. The corresponding methyl substituents in position 3 of the pyrazole rings are detected at 2.79 ppm. The protons of the methylene bridge are observed at 6.11 ppm. The success of the formylation reaction can be observed by the signal of the aldehyde proton at 9.93 ppm. The analysis via 13C NMR spectroscopy also shows the methyl substituents as the most upfield signals with chemical shifts of 10.1 and 12.7 ppm, respectively. The carbon atom of the methylene bridge is found at 59.1 ppm. The signals at 118.8, 146.5 and 151.8 ppm can be assigned to the pyrazole carbon atoms. The signal of an aldehyde carbon atom at 185.0 ppm also confirms the effected synthesis.

59 3 Results and Discussion

3.1.2 Bis(3,5-dimethyl-4-vinylpyrazol-1-yl)methane (bdmvpzm) (2)[35]

In the next step, the obtained bisaldehyde 1 was reacted in a Wittig reaction. By doing so, the desired vinyl linker was introduced, which is crucial for the desired copolymerization capability of the resulting ligand. The synthetic route reported by Türkoglu et al. was employed.[35] + − The required ylid [Ph3P -C H2 ↔ Ph3P=CH2] was generated in situ from the reaction of triphenyl-methyl-phosphoniumbromide with potassium tert-butoxide in tetrahydrofuran. After the addition of compound 1, the desired vinyl substituted product 2 is formed. After puriﬁcation of the crude product via column chromatography to remove triphenylphosphine oxide, which is generated during the reaction, compound 2 could be obtained in yields of 80 % referring to 1.

O O N N [Ph3P-CH2 Ph3P=CH2] N N N N N N

1 2

Scheme 3.2: Synthesis of Bis(3,5-dimethyl-4-vinylpyrazol-y-1l)methane (bdmvpzm) (2).[35]

The 1H NMR spectrum of the resulting compound shows signals of the methyl groups at the C5 and C3 carbon atoms of the pyrazole rings at 2.27 and 2.47 ppm. The introduced vinyl linkers create an AMX system in the spectrum, which proves the successful formation of the desired compound.[184] The terminal protons of the vinyl groups result in a doublet of doublet at 5.14 ppm (Z) and 5.29 (E). The corresponding coupling constant for the 2 3 geminal coupling is calculated to J H,H = 1.4 Hz. The J H,H(E) amounts to 17.7 Hz and 3 for J H,H(Z), 11.4 Hz is measured. The non terminal protons of the vinyl groups also split up in doublets of doublets at a chemical shift of 6.48 ppm. Their coupling constants are 3 J H,H = 11.5 Hz and 17.9 Hz, respectively. The CS symmetry of compound 2 is reﬂected by these results. The singlet at 6.09 ppm can be assigned to the protons of the methylene bridge. Furthermore, 13C NMR spectroscopy was performed. The spectrum shows the methyl signals at 10.2 and 13.6 ppm. The bridging methylene carbon atom is detected at 60.7 ppm.

The resonances of the vinyl groups can be found at 112.8 ppm (=CH2) and at 127.4 ppm (-CH=). The remaining signals at 116.5, 138.0 and 146.8 ppm can be assigned to the carbon atoms of the pyrazole rings.

60 3.1 Oxo-Transfer Catalysis by Chelate and Scorpionate Oxomolybdenum Complexes

3.1.3 [MoO2Cl2(bdmvpzm)] (3) For the synthesis of a molybdenum(VI)-dioxo complex of the N,N coordinating ligand bdmvpzm (2), the designated metal fragment molybdenum(VI) dichloride dioxide was

ﬁrst dissolved in tetrahydrofuran, to obtain the solvent stabilized [MoO2Cl2(THF)2]. To the resulting solution, 2 was added, which led to the precipitation of the desired N,N’ complex 3 as a yellow-green solid. This procedure followed roughly the synthesis of molybdenum(VI) cis-dioxo complexes with polypyrazolylmethane ligands published by Santos et al.[149]

N N [MoO2Cl2] N N Cl N N THF N N Mo Cl O 2 O 3

Scheme 3.3: Synthesis of [MoO2Cl2(bdmvpzm)] (3).

The 1H NMR spectrum of complex 3 reveals the two methyl groups at the C5 carbon atoms of the pyrazole rings at 2.15 ppm. The corresponding groups at the C3 carbon atoms have a chemical shift of 2.44 ppm. As for the free ligand, the vinyl protons split up into doublets of doublets at 5.09 ppm (Z) and 5.26 (E), respectively. The corresponding coupling constants 3J amount to 11.6 Hz for the former and 17.9 Hz for the latter. The 2J coupling constants were each of 1.2 Hz. The singlet at 6.50 ppm can be assigned to the protons of the methylene bridge. The remaining non terminal vinyl protons are found 3 3 at 6.50 ppm, with coupling constants of J H,H = 17.9 Hz and J H,H = 11.7 Hz. In the 13C NMR spectrum, the two methyl substituents of the C5 carbon atoms of the pyrazole rings appear at 9.69 ppm, while their counterparts at the C3 carbon atoms appear at 13.5 ppm. The carbon atom of the methylene bridge is detected at 59.0 ppm. The vinyl linker appears at a chemical shift of 112.3 ppm in the case of the terminal carbon atoms and of 127.6 ppm in the case of the non terminal carbon atoms. The remaining signals at 115.2, 138.0 and 145.8 ppm can be assigned to the carbon atoms of the pyrazole rings. The complex was analyzed via IR spectroscopy as well. Therefore, the metal precursor molybdenum(VI) dichloride dioxide was used as a reference. In the latter, the two charac- −1 teristic Mo=O bands can be found at νe = 959 (νsym) and 915 cm (νasym). The spectrum −1 of 3 shows these bands as well at νe = 944 (νsym) and 917 cm (νasym). These ﬁndings agree with the literature values of similar compounds published by Santos et al., which indicate a successful complexation.[149]

61 3 Results and Discussion

In addition, the composition of the complex was determined via elemental analysis, which conﬁrmed the desired compound. However, it was not possible to verify 3 via mass spectroscopy (ESI-MS). Neither the characteristic isotopic pattern of molybdenum, nor fragments in the relevant m/z range could be found. However, it was possible to obtain a single crystal suitable for X-ray structure determination by layering a solution of 3 in dichloromethane with n-hexane.

Figure 3.3: Molecular structure of [MoO2Cl2(bdmvpzm)] (3). Thermal ellipsoids are drawn at the 50 % probability level. Hydrogen atoms have been omitted for clarity.

The resulting molecular structure of 3 is depicted in figure 3.3. The molybdenum(VI) center therein is sixfold coordinated, which can be best described as a distorted octahedron. The ligand itself is κ2 N,N coordinated, as it was expected. The bond lengths Mo-Cl1 and Mo-Cl2 of 2.3806(5) and 2.3738(5) Å are almost identical, as are the Mo- N bonds with 2.3575(19) and 2.3591(17) Å and the Mo-O bonds with 1.6982(16) and 1.6961(15) Å. While this is a normal bond length for a molybdenum oxygen double bond, the Mo-N bonds are slightly longer than expected (2.2 Å), which can be attributed to the trans influence of the oxo groups.[151] On the other hand, the O-Mo-N angles differ by 4◦. Furthermore, the axial Cl-Mo-Cl angle is slightly bent with 162.669(18)◦. Both of the vinyl groups are turned out of the pyrazole plane. The torsion angle C12-C13- C16-C17 amounts to 39.163(9)◦ and is directed to the underside of the butterfly shaped molecule, in which both planes, that are spanned by the pyrazole rings, stand in an angle

62 3.1 Oxo-Transfer Catalysis by Chelate and Scorpionate Oxomolybdenum Complexes of 134.80◦. The other vinyl moiety is turned towards the upper side for 38.096(9)◦. Yet both of the vinyl linkers are directed towards the metal center.

Distances (Å) Mo-Cl1 2.3806(5) Mo-N21 2.3591(17) Mo-Cl2 2.3738(5) N11-N12 1.373(2) Mo-O1 1.6982(16) N21-N22 1.374(2) Mo-O2 1.6961(15) C16-C17 1.322(4) Mo-N11 2.3575(19) C26-C27 1.323(3)

Angles (deg) Cl1-Mo-Cl2 162.669(18) Cl2-Mo-N21 83.76(4) Cl1-Mo-O1 95.14(6) O1-Mo-O2 104.08(8) Cl1-Mo-O2 97.08(5) O1-Mo-N11 168.68(7) Cl1-Mo-N11 82.77(4) O1-Mo-N21 91.16(7) Cl1-Mo-N21 81.61(4) O2-Mo-N11 87.23(7) Cl2-Mo-O1 94.38(6) O2-Mo-N21 164.75(7) Cl2-Mo-O2 94.60(5) C12-C13-C16-C17 39.163(9) N11-Mo-N21 77.53(6) C22-C23-C26-C27 38.096(9) Cl2-Mo-N11 85.06(4)

Table 3.1: Selected interatomic distances (Å) and angles (deg) for compound 3.

In comparison to other complexes containing a MoO2Cl2N2 moiety, no significant difference to the angles or bond lengths could be found.[149,185] A list of selected interatomic distances and angles is shown in table 3.1. This shows, that there is no influence of the vinyl linker groups on the coordination site of bdmvpzm (2), as it was already shown before by Türkoglu et al. for the N,N,O coordinating bis(3,5-dimethyl-4-vinylpyrazol-1-yl)acetic acid (Hbdmvpza) (4).[35]

3.1.4 Bis(3,5-dimethyl-4-vinylpyrazol-1-yl)acetic acid (4)[35]

Having obtained a N,N coordinated molybdenum(VI) complex, the next step was to functionalize compound 2 further to obtain a κ3 N,N,O coordinating derivative bis(3,5- dimethyl-4-vinylpyrazol-1-yl)acetic acid 4, which was first synthesized by Türkoglu et al. in 2010.[35] This ligand is capable off resembling the desired “2-His-1-carboxylate triade” motif, which has a wide range of applications in bioinorganic chemistry (see figure 1.2 in chapter 1.1.2).[14,15,35] The necessary carboxylate function was introduced at the methylene bridge, as depicted in scheme 3.4. Therefore, the original bis(pyrazolyl)acetato ligand synthesis of Otero

63 3 Results and Discussion et al. was employed.[10] The methylene bridge was deprotonated with n-butyllithium in tetrahydrofuran at a temperature of −78 ◦C. Subsequent treatment with a dry stream of carbon dioxide at −20 ◦C followed by aqueous workup of the reaction mixture led to the formation of the desired carboxylic acid 4 in yields of 68 %.

O OH

1. n-BuLi N N 2. CO2 N N N N THF N N

2 4

Scheme 3.4: Synthesis of bis(3,5-dimethyl-4-vinylpyrazol-1-yl)acetic acid 4 according to Türkoglu et al.[35]

In the 1H NMR spectrum of Hdmvpza 4, there are two singlets for the methyl substituents at the pyrazole carbon atoms 3 and 5 at 2.32 and 2.28 ppm, respectively. Furthermore, the AMX system, that could already be found in the spectrum of bdmvpzm (2), can be observed once again.[184] It is caused by the vinyl moieties and consists of one doublet of doublets caused by the terminal vinyl protons at chemical shifts of 5.24 ppm (Z) and 2 5.34 ppm (E). The corresponding coupling constant amounts to J H,H = 0.8 Hz for the 3 3 geminal couplings. The constants J H,H(E) and J H,H(Z) were determined to 17.9 Hz and 11.6 Hz. Another doublet of doublets is caused by the non terminal vinyl protons 3 3 at 6.45 ppm. The corresponding coupling constants are J H,H = 11.7 Hz and J H,H =

17.9 Hz, respectively. These findings reflect the C S symmetry of compound 4. The most downfield signal at 6.45 ppm can be assigned to the proton of the methine bridge. The 13C NMR spectrum shows the methyl signals at chemical shifts of 10.0 and 13.4 ppm. The signal at 70.5 ppm could be assigned to the bridging carbon atom. The terminal carbon atoms of the vinyl linkers could be observed at 114.8 ppm, whereas the non terminal carbon atoms of the linkers lead to signals at 128.5 ppm. Furthermore, the carbon atoms of the pyrazole rings lead to singlets at 115.7 (C4), 137.3 (C5) and 145.1 ppm (C3). The carbon atom of the carboxylate group is detected at 165.4 ppm.

64 3.1 Oxo-Transfer Catalysis by Chelate and Scorpionate Oxomolybdenum Complexes

3.1.5 [MoO2Cl(bdmvpza)] (5) After the synthesis of Hbdmpvza (4), it was possible to synthesize the corresponding N,N,O coordinated complex of molybdenum(VI) dichloride dioxide. In the course of the reaction, one chlorido ligand was abstracted to maintain a sixfold coordination. The synthetic method, that was employed was based on the synthetic route of compound 3, except of the addition of potassium tert-butoxide to deprotonate the carboxylate donor function. A similar complex [MoO2Cl(bdmpza)] was already published by Hammes et al., yet without the additional vinyl linker substituents.[151] While the compound, that was obtained by Hammes et al. was a white solid, the vinyl substituted derivative is of a red-brown color.

O OH

N N [MoO2Cl2] N N THF O O N N N N Mo 4 Cl O O 5

Scheme 3.5: Synthesis of [MoO2Cl(bdmvpza)] (5).

Nevertheless, the findings that were revealed in the 1H NMR spectrum of 5, agree with the results, that were found for the [MoO2Cl(bdmpza)] complex of Hammes et al. De- pending on the solvent, the two isomers, that are depicted in figure 3.4 can be found in different ratios.[151] The cis isomer is defined as the isomer with the oxo groups cis to the oxygen donor of the ligand while the trans isomer has one oxo group trans to the oxygen donor.[151] Yet it was not possible to separate them from each other for analysis. This is not surprising, considering, that the difference in energy between the two isomers for the very similar [MoO2Cl(bdmpza)] complex was calculated via DFT calculations to only 2.58 kcal/mol.[151]

N N N N O O O O N N N N Mo Mo Cl O O O O Cl

Figure 3.4: Isomers: (left: trans-isomer, right: cis-isomer) of [MoO2Cl(bdmvpza)] (5).

The spectrum implies the loss of the former C S symmetry for one of the isomers. While the two isomers could not be separated, they could be distinguished in the 1H NMR spectrum.

65 3 Results and Discussion

The methyl protons of the symmetric cis isomer could be detected at 2.17 and 2.26 ppm, respectively. The AMX system caused by the vinyl moieties could be observed as well.[184] The terminal vinyl protons are detected at 5.12 (Z) and 5.28 ppm (E). The corresponding 2 coupling constant amounts to J H,H = 1.0 Hz for the geminal couplings. The constants 3 3 J H,H(E) and J H,H(Z) were determined to 18.0 Hz and 11.5 Hz. Another doublet of doublets is caused by the non terminal vinyl protons at 6.51 ppm. The corresponding 3 3 coupling constants are J H,H = 11.7 Hz and J H,H = 17.9 Hz, respectively. Furthermore the singlet at 7.27 ppm could be assigned to the methine bridge. In the case of the asymmetric trans isomer, the four methyl groups split up into four singlets at 2.54, 2.61, 2.71 and 2.79 ppm. The AMX systems appear as multiplets at 5.41 and 6.57 ppm, which could not be resolved. The singlet at 7.05 ppm was assigned to the methine bridge of the trans isomer. The analysis of the 13C NMR of compound 5 proved easier. Due to the lower time resolution of 13C NMR spectroscopy, only one set of signals could be observed. Thus, the methyl substituents in position 5 and 3 of the pyrazole rings could be detected at 9.91 and 13.5 ppm. The bridging carbon atom was found at 71.3 ppm. Furthermore, the carbon atoms of the vinyl moieties can be assigned to the signals at 112.7 ppm in the case of the terminal atoms, while the non terminal carbon atoms can be detected at 127.4 ppm. The remaining signals at 115.7, 138.4 and 145.6 ppm are caused by the carbon atoms of the pyrazole rings, whereas the singlet at 165.9 ppm derives from the carboxylate group. While it was not possible to obtain a molecular structure of compound 5, the structure of Hammes et al., which is depicted in ﬁgure 3.5, should,[151] apart from the lacking vinyl linkers, closely resemble the structure of compound 5. This similarity was already observed for the corresponding N,N coordinated complex [MoO2Cl2(bdmvpzm)] (3) and its non vinyl substituted counterpart by Santos et al.,[149] as stated in chapter 3.1.3.

νsym(Mo=O) νasym(Mo=O)

[MoO2Cl2] 959 915

[MoO2Cl2(bdmvpzm)] (3) 944 917

[MoO2Cl(bdmvpza)] (5) 942 911 [151] [MoO2Cl(bdmpza)] 941 910

Table 3.2: IR data of selected molybdenum(VI) dioxo compounds in cm−1.

Another argument speaking in favor of the isostructurality of the two complexes is delivered by the results of the IR measurements (KBr). As mentioned in 3.1.3, the vibrational −1 −1 bands of the metal educt [MoO2Cl2] are found at νsym = 959 cm and νasym = 915 cm . −1 The corresponding absorptions in compound 5 can be observed at νsym = 942 cm and −1 νasym = 911 cm , which shows the successful complexation. The IR absorption bands, −1 that were found by Hammes et al. for [MoO2Cl(bdmpza)], are νsym = 941 cm and

66 3.1 Oxo-Transfer Catalysis by Chelate and Scorpionate Oxomolybdenum Complexes

−1 [151] −1 νasym = 910 cm , which amounts to a difference of only 1 cm in both values in comparison to 5. This clearly speaks for a very similar coordination sphere. A list of the mentioned absorption bands for comparison is shown in table 3.2. As can be seen in figure 3.5, the molybdenum(VI) center is sixfold coordinated, as for compound 3. However, one chlorido ligand was exchanged by the carboxylate donor group of the ligand. Nevertheless, the coordination motif of a distorted octahedron is preserved. The Mo=O bonds are slightly elongated (1.754(8) and 1.769(7) Å) in comparison to compound 3 (1.693(3) Å). The trans influence of the oxo group on the Mo-N can be observed again. The corresponding bond has a length of 2.323(9) Å compared to the bond trans to the chlorido ligand with only 2.212(9) Å.[151]

[151] Figure 3.5: Molecular structure of [MoO2Cl(bdmpza)] by Hammes et al. Thermal ellipsoids are drawn at the 50 % probability level. Hydrogen atoms have been omitted for clarity. The structure is compositionally disordered. The nature of disorder is however indicating that the trans isomer is predominant.[151]

67 3 Results and Discussion

3.1.6 Copolymers containing bdmvpzm (2) and Hbdmvpza (4)[35]

The two vinyl substituted ligands bdmvpzm (2) and Hbdmvpza (3) were copolymerized with two comonomers suitable for vinylogous polymerizations. On the one hand, the linear polymerizing methyl methacrylate (MMA) and on the other hand the crosslinking ethylene glycol dimethacrylate (EGDMA) were used for this purpose.

x y z O O NN NN

CO2H CO2H N N N N

x y z O O NN NN

CO2H CO2H N N O O N N

Figure 3.6: Molecular structures of Hbdmvpza copolymers with MMA (top) and EGDMA (bottom).[35]

The reactions were carried out in dry xylenes at a temperature of 85 ◦C. In order to increase the surface area of the resulting compounds, xylenes were used as solvent for its porogenic properties. This was necessary to preserve the reactivity of the obtained copolymers and ensure access to the embedded coordination site for metal fragments. The copolymerization process was initialized by the addition of the radical starter azobisisobutyronitrile (AIBN). The possible molecular structures, which result from the reactions depicted in scheme 3.6, are depicted in ﬁgure 3.6. The amount of incorporated ligand moieties embedded in the copolymers was in a similar magnitude as reported earlier by Gazi Türkoglu.[35,186] However, in contrast to these earlier results, no ﬁrst fraction of the MMA copolymers with

68 3.1 Oxo-Transfer Catalysis by Chelate and Scorpionate Oxomolybdenum Complexes EGDMA / MMA

AIBN N N MMA/EGDMA N N N N xylene, 85°C N N

2 EGDMA / MMA P6/P7

O OH O OH EGDMA / MMA

AIBN N N MMA/EGDMA N N N N xylene, 85°C N N

4 EGDMA / MMA P8/P9

Scheme 3.6: Synthesis of copolymers of bdmvpzm (2) and Hbdmvpza (3) with MMA or EGDMA. an increased amount of ligand incorporation could be obtained as precipitate (compare chapter 1.2.5). The most likely reason for this is the higher starting concentration of MMA in the reaction feedstock (see table 3.3).

Polymer Ligand Added Ligand/monomer Ligand/polymer Yield monomer monomer [mmol/g][a] [mmol/g][b] [%][c] P6 bdmvpzm MMA 0.294 0.443 28.1 P7 bdmvpzm EGDMA 0.267 0.310 95.8 P8 Hbdmvpza MMA 0.294 0.624 18.4 P9 Hbdmvpza EGDMA 0.265 0.228 96.5

Table 3.3: Incorporation of bdmvpzm 2 and Hbdmvpza 4 in copolymers with MMA and EGDMA. [a] Ratio related to composition feed. [b] Ratio related to composition in the ﬁnal polymer. [c] Weight percent related to total weight of monomers in feed.

As can be seen in table 3.3, the ligand incorporation in the MMA copolymers is still higher than for the EGDMA copolymers. As stated in chapter 1.2.5, this is probably due to the higher reactivity of the crosslinking ligand monomers, in comparison to the MMA monomers, which therefore react preferentially with each other.[35] Yet, the yields of the copolymerization with EGDMA were almost quantitative.

69 3 Results and Discussion

The values listed in table 3.3 were determined by the % N value of the elemental analysis of the polymers. The calculations were carried out according to the following equation:[35]

mmol Ligand % N = · 10 g P olymer 4 · 14 g · mol−1

3.1.7 Molybdenum Containing Copolymers

In general, there are two diﬀerent possible routes to obtain molybdenum containing copolymers of the bdmpvz (2) and Hbdmvpza (4) ligands. On the one hand, the previously presented copolymers P6, P7, P8 and P9 can be charged with a molybdenum fragment. On the other hand, the complexes 3 and 5 can be embedded in copolymers.

3.1.7.1 Treatment of Copolymers with [MoO2Cl2(THF)2]

The coordination of molybdenum(VI) dichloride dioxide to the copolymers P6, P7, P8 and P9 was carried out in tetrahydrofuran. The N,N,O coordinating polymers P8 and P9 were deprotonated with potassium tert-butoxide prior to the addition of the metal fragment. To compensate for the increased sterical hindrance of the polymer structure, the reaction temperature was raised to 50 ◦C. EGDMA / MMA EGDMA / MMA

N N [MoO2Cl] N N Cl N N THF, 50 °C N N Mo EGDMA / MMA P6/P7 EGDMA / MMA Cl O O P6-Mo/P7-Mo

O OH EGDMA / MMA EGDMA / MMA

1. KOtBu

N N 2. [MoO2Cl2] N N O O N N THF, 50 °C N N Mo EGDMA / MMA P8/P9 EGDMA / MMA Cl O O P8-Mo/P9-Mo

Scheme 3.7: Synthesis of Synthesis of P6-Mo, P7-Mo, P8-Mo and P9-Mo.

It was expected, that the EGDMA polymers would exhibit a lower amount of complex- ated molybdenum, due to the highly crosslinked structure of the compound, which causes

70 3.1 Oxo-Transfer Catalysis by Chelate and Scorpionate Oxomolybdenum Complexes a high level of sterical hindrance in these polymers. The resulting metal loaded copolymers were analyzed via atomic absorption spectroscopy (AAS) after chemical digestion of the respective samples. The obtained results conﬁrmed these expectations, as listed in table 3.4. As can be seen, the values revealed a higher incorporation of molybdenum in MMA polymers. In P8-Mo 78.5 % of the available coordination sites were occupied and 61.2 % in P6-Mo. In contrast, the highly crosslinked EGDMA polymers exhibited low occupation ratios of only 14.8 (P7-Mo) and 8.41 % (P9-Mo).

Polymer Ligand Copolymer Ligand incorpo- Metal/polymer Occupancy monomer ration [mmol/g] [mmol/g] [%] P6-Mo bdmvpzm MMA 0.443 0.271 61.2 P7-Mo bdmvpzm EGDMA 0.310 0.0459 14.8 P8-Mo Hbdmvpza MMA 0.624 0.490 78.5 P9-Mo Hbdmvpza EGDMA 0.228 0.0192 8.41

Table 3.4: Molybdenum content of the polymers after treatment with [MoO2Cl2] as determined by AAS.

The question, why in the case of the MMA copolymers the N,N,O coordinating ligand moieties show higher degrees of occupation, while the opposite is the case for the EGDMA polymers, cannot be easily answered. A possible explanation for these findings is, that in the relatively flexible MMA copolymers, the influence of the higher coordination potential of the κ3 coordinating N,N,O binding sites dominates. In the already highly crosslinked EGDMA polymer however, the additional carboxylate moiety might block access to the coordination site from one side, thus further increasing the sterical hindrance and thereby hampering the complexation. As mentioned above, Gazi Türkoglu reported, that the κ2 or κ3 coordination mode was not influenced by the polymerization process (see chapter 1.2.6).[35,186] For the Ru- and Mn complexes reported earlier, IR studies strongly indicated an unchanged κ3-N,N,O coordination of the respective metal center.[35,186] In order to confirm, that the same applies to the molybdenum(VI) compounds discussed herein, the N,N,O coordinated were analyzed via IR spectroscopy. Unfortunately, the oxo molybdenum vibrations appear in the spectra in an area, where the polymer itself is absorbing, as well. The results for P8-Mo are depicted in figure 3.7. For comparison, the spectra of polymethylmethacrylate (PMMA), the homopolymer of MMA and of the monomeric complex

[MoO2Cl(bdmvpza)] (5) were added. The spectrum of compound 5 (ﬁgure 3.7 (a)) shows the two characteristic Mo=O vibrational bands. As discussed in chapter 3.1.5, they ap- −1 −1 pear at νe = 942 cm and νe = 911 cm . These vibrations were also found in the spectrum

71 3 Results and Discussion

−1 −1 of the corresponding copolymer P8-Mo at νe = 943 cm and νe = 913 cm . As the vibrations appear at almost identical wave numbers, it can be assumed, that the coordination motif is unchanged.

(a)

(b)

(c)

Figure 3.7: IR spectra of (a) [MoO2Cl(bdmvpza)] (5), (b) PMMA and (c) P8-Mo.

A comparison of the three spectra in ﬁgure 3.7 shows, that the spectrum of P8-Mo (c) obviously resembles a superposition of the absorptions of the free complex [MoO2Cl- (bdmvpza)] (5 (a) and PMMA (b). The same results were found for the copolymer P9-Mo. There, the vibrations were −1 −1 detected at νe = 944 cm as a shoulder and νe = 910 cm as a weak band.

72 3.1 Oxo-Transfer Catalysis by Chelate and Scorpionate Oxomolybdenum Complexes

3.1.7.2 Copolymerization of [MoO2Cl2(bdmvpzm)] (3) and

[MoO2Cl(bdmvpza)] (5)

The second possibility to obtain molybdenum containing polymers was the copolymerization of the complexes [MoO2Cl2(bdmvpzm)] (3) and [MoO2Cl(bdmvpza)] (5) with MMA and EGDMA. To do so, the complex monomers were dissolved in acetonitrile and heated to a temperature of 65 ◦C. As before, the polymerization was started by the addition of AIBN. The results of the copolymerization process can be seen in table 3.5, as determined by AAS. EGDMA / MMA

AIBN N N MMA/EGDMA N N Cl Cl N N MeCN, 65 °C N N Mo Mo

Cl O EGDMA / MMA Cl O O O 3 P10/P11 EGDMA / MMA

AIBN N N MMA/EGDMA N N O O O O N N MeCN, 65 °C N N Mo Mo

Cl O EGDMA / MMA Cl O O O 5 P12/P13

Scheme 3.8: Copolymerization of [MoO2Cl2(bdmvpzm)] (3) and [MoO2Cl(bdmvpza)] (5) with MMA and EGDMA.

As already mentioned, the MMA copolymer bares a lower activity in the polymerization process, since it is not a crosslinker. Therefore, the complex incorporation is comparatively high. The opposite applies to EGDMA. The corresponding polymers expose a low level of complex incorporation. While a change of the coordination scheme upon polymerization seems unlikely, IR spectroscopy of the resulting compounds was carried out, nevertheless. Table 3.6 shows the corresponding IR data. For comparison, the respective absorptions of the monomeric complexes were added. These results show, that the compounds obtained by polymerization subsequent to complexation, exhibit the same absorption characteristics as the aforementioned polymers (see chapter 3.1.7.1). In comparison with the monomeric complexes, only slight shifts of

73 3 Results and Discussion

Polymer Complex Copolymer Complex/monomer Metal/polymer monomer monomer [mmol/g][a] [mmol/g]

P10 MoO2Cl2(bdmvpzm) (3) MMA 0.211 0.646

P11 MoO2Cl2(bdmvpzm) (3) EGDMA 0.191 0.0334

P12 MoO2Cl(bdmvpza) (5) MMA 0.208 0.401

P13 MoO2Cl(bdmvpza) (5) EGDMA 0.188 0.0307

Table 3.5: Molybdenum content of the copolymers obtained by copolymerization of [MoO2Cl2- (bdmvpzm)] (3) and [MoO2Cl(bdmvpza)] (5) with MMA and EGDMA as determined by AAS. (a) Ratio related to composition feed. the wave numbers were observed. This argues for an unchanged coordination motif. P11 however did show the corresponding Mo=O bands only as weak shoulders. This was unexpected, since the metal content of the polymer appeared to be suﬃciently high. The most likely explanation is, that the corresponding absorptions were overlaid by the absorptions of the copolymer. Another explanation could be an unwanted side reaction. Yet, the most relevant side reaction, that could have occurred, is the reaction with traces of moisture during the polymerization process. This might have led to the formation of oxido-bridged dimers or oxidodiperoxo molybdenum(VI) centers, linked by µ2-bridging oxygen atom. Such compounds would however still show strong absorptions in the same region, which were not observed either.[187,188]

−1 Polymer νe [cm ] monomeric complexes P10 947, 915 944, 917 (3) P11 944, 919[a] P12 941, 911 942, 911 (5) P13 943, 911

Table 3.6: Observed Mo=O vibrational bands of P10, P11, P12 and P13 (KBr). [a] as weak shoulders

3.1.8 Oxygen Atom Transfer Catalysis

The previously presented complexes and copolymers were now applied in an oxygen atom transfer (OAT) reaction. More speciﬁcally the transfer of an oxygen atom from dimethyl sulfoxide to triphenylphosphine was attempted. This reaction resembles the catalytic activity of the DMSO reductase (see chapter 1.5.2). On the one hand, this serves as a veriﬁcation, if such a system can be useful as model for the DMSO reductase. On the other hand, the reaction may serve as a benchmark for the whole concept of the 4-vinyl substituted bis(pyrazolyl)acetic acids and their reactivity in the copolymerized state.

74 3.1 Oxo-Transfer Catalysis by Chelate and Scorpionate Oxomolybdenum Complexes

DMS PPh3

Cl NN VI Mo Cl O O Cl Cl NN NN V Mo Mo Cl O Cl O O O

S PPh3

Cl NN IV Mo Cl O OPPh DMSO 3

Scheme 3.9: Proposed catalytic cycle and relevant oxidation states for the reduction of DMSO by the presented molybdenum complexes and their copolymers (here: [MoO2Cl2(bdmvpzm)] (3)).

The catalysis was carried out in deoxygenated dimethyl sulfoxide to exclude this alternative source of oxygen atoms. 200 equivalents of triphenylphosphine were dissolved, before the catalysts were added. After 24 hours in the case of polymer catalysts and 6 hours in the case of the monomeric complexes, samples were taken and analyzed via 1H and 31P NMR spectroscopy.

Catalyst ligand/complex monomer copolymer

P10 MoO2Cl2(bdmvpzm) (3) MMA

P11 MoO2Cl2(bdmvpzm) (3) EGDMA

P12 MoO2Cl(bdmvpza) (5) MMA

P13 MoO2Cl(bdmvpza) (5) EGDMA P6-Mo bdmvpzm MMA P7-Mo bdmvpzm EGDMA P8-Mo Hbdmvpza MMA P9-Mo Hbdmvpza EGDMA

Table 3.7: Composition of copolymers employed in catalytic DMSO reduction.

1H NMR spectra were used to monitor the release of dimethyl sulﬁde, which was found at a chemical shift of 1.98 ppm. Furthermore, the formation of triphenylphosphine oxide was monitored via 31P NMR spectroscopy. The yields of the catalytic reactions were calculated by the integration of the corresponding signals in the 31P NMR spectra. The results of the experiments are shown in table 3.8. For better comparison, the compo-

75 3 Results and Discussion

Catalyst t neduct (t0) ncatalyst neduct (t) nproduct (t) y TON TOF [h] [mmol] [µmol] [mmol] [mmol] [%] [10−5 s−1] - 24 1.50 7.50 1.50 0 0 0 0 3 6 1.50 7.50 0.660 0.840 56 112 519 5 6 1.50 7.50 0.675 0.825 55 110 509 P10 24 1.50 7.50 0.195 1.31 87 174 201 P11 24 1.50 7.50 1.49 0.0200 1 2 2.31 P12 24 1.50 7.50 0.960 0.540 36 72 83.3 P13 24 1.50 7.50 1.14 0.360 24 48 55.6 P6-Mo 24 1.50 7.50 0.165 1.34 89 178 206 P7-Mo 24 1.50 7.50 0.435 1.07 71 142 164 P8-Mo 24 1.50 7.50 0.840 0.660 44 88 102 P9-Mo 24 1.50 7.50 1.38 0.120 8 16 18.5

Table 3.8: Results of the catalytic reduction of dimethyl sulfoxide. sition of all of the involved copolymers are listed in table 3.7. The measurements display, that all of the employed materials showed OAT activity and thus relevant catalytic activity concerning DMSO reductase models. As control experiment, dimethyl sulfoxide was stirred with triphenylphosphine without additional catalyst. However, no reaction could be observed in this case. The calculations of yields (y), turnover numbers (TON) and turnover frequencies (TOF) were calculated according to the following equations:

n (t) y = product · 100% nreactant(t0)

n (t) TON = product ncatalyst

TON TOF = t

In general, all of the EGDMA based copolymers revealed a lower activity than their MMA based counterparts. This was to expect, since the latter polymers are significantly less crosslinked. Furthermore, the copolymers, which were charged with molybdenum subsequent to the polymerization process show a higher activity than the corresponding polymers, in which the finished complexes were embedded. The reason for this correlation presumably lies in the amount of active metal sites. While many metal centers can be blocked during the polymerization process, if the final complexes are incorporated, the first mentioned

76 3.1 Oxo-Transfer Catalysis by Chelate and Scorpionate Oxomolybdenum Complexes polymers P6-Mo to P9-Mo contain metal fragments only at accessible active sites. Thus it is reasonable, that their relative catalytic activity is higher. The overall results show that the obtained materials are potential models, mimicking oxomolybdenum enzymes as shown above, especially for DMSO reductases. Nevertheless, the transfer of oxygen to triphenylphosphine is only a starting point, since it is no bio- relevant oxygen acceptor. Therefore, further studies have the be conducted on this topic.

77 3 Results and Discussion

3.2 4-Ethynyl Substituted Pyrazole Based Ligands

The second part of this thesis is about the introduction of ethynyl linkers in position 4 of the pyrazole rings of pyrazole based ligands. While ﬁrst compounds with vinyl groups in this position have already been reported by Gazi Türkoglu,[35,186] this is a new approach to add additional functionality to the well established system of bis(pyrazolyl)acetato or bis(pyrazolyl)methane scorpionate and chelate ligands. Acetylene moieties oﬀer a great potential for coupling reactions like the Sonogashira or the Glaser coupling reactions as well as Click chemistry reactions like the copper catalyzed azide-alkyne cycloaddition (CuAAC) or the Huisgen cycloaddition, as depicted in scheme 3.10.

HN R' N

R' Br

HN N N R' N HN R' I HN 3 R' N N N N R'

HN N

HN N N NH

Scheme 3.10: Possible reactions of acetylene linker groups.

These reactions provide relatively mild ways to functionalize ligands and the complexes thereof. Examples of such functionalizations could be the introduction of fluorophores, which could be triggered by paramagnetic fluorescence quenching, induced by the coordinated metal centers. Furthermore, moieties that are capable of promoting the solubility of the resulting complexes could be attached easily to overcome solubility issues. In order to obtain such compounds, different reaction pathways were to be used, as will be discussed in the following chapter. Two general approaches are to be mentioned here. On the one hand, the introduction of an ethynyl linker to an already coupled pair of pyrazole

78 3.2 4-Ethynyl Substituted Pyrazole Based Ligands moieties and on the other hand the synthesis of ethynyl substituted pyrazole derivatives, which should then be reacted to the corresponding ligands.

79 3 Results and Discussion

3.2.1 Bis(4-(2,2-dibromovinyl)-3,5-dimethylpyrazol-1-yl)- methane (14)

In order to obtain an ethynyl substituted bis(pyrazol-1-yl)methane ligand from bis(3,5- dimethyl-4-formylpyrazol-1-yl)methane (1), Corey-Fuchs conditions were chosen. The ﬁrst step of this two step reaction is the formation of a dibromovinyl species from an aldehyde precursor in a Wittig type reaction. To do so, 57 was treated with tetrabro- momethane in the presence of triphenylphosphine and triethylamine. After puriﬁcation via column chromatography, the product 14 could be obtained as a violet solid in good yields.

Br Br O O Br Br N N CBr4, PPh3 N N N N NEt3 N N H H 1 14

Scheme 3.11: Synthesis of Bis(4-(2,2-dibromovinyl)-3,5-dimethylpyrazol-1-yl)methane (14).

The 1H NMR spectrum of compound 14 shows two singlets corresponding to the methyl substituents of the pyrazole rings at 2.11 and 2.38 ppm. Compared to the educt, an upfield shift is noticed. The protons of the methylene bridge are detected at 6.01 ppm. The most striking difference in comparison to the educt spectrum is the signal of the proton adjacent to the reaction site. It is shifted from 9.93 ppm to 7.18 ppm in the product NMR spectrum. The 13C NMR spectrum is very similar to the educt spectrum as far as the bis(pyrazol- 1-yl)methane moiety is concerned, with the methyl groups at 11.6 and 13.2 ppm, the bridging carbon atom at 54.0 ppm and the carbon atoms of the pyrazole rings at chemical shift of 116.1, 138.8 and 147.3 ppm. The two carbon atoms of the dibromovinyl moiety clearly indicate the product formation with signals at 61.0 and 93.0 ppm. Furthermore, the product 14 could be confirmed by elemental analysis. Due to the high molecular mass of the bromide residues, this is a conclusive proof for the successful product formation.

80 3.2 4-Ethynyl Substituted Pyrazole Based Ligands

3.2.2 Bis(4-ethynyl-3,5-dimethylpyrazol-1-yl)methane (bedmpzm) (15)

The second step of the Corey-Fuchs reaction consists of the formation of the desired ethynyl substituted product by treatment of the dibromovinyl precursor 14 with two equivalents of n-butyllithium. The ﬁrst equivalent leads, after initial lithiation, to the rearrangement to a terminal alkyne. This alkyne reacts with the second equivalent to the corresponding lithium acetylide, which is protonated to the desired product after aqueous workup.[189] Standard conditions for this reaction suggest, as common for lithiation reactions with n-butyllithium, tetrahydrofuran as solvent and a temperature of −78 ◦C.[190] Yet these reaction conditions lead to decomposition of the substrate. The reaction could not be carried out in tetrahydrofuran at any other temperature up to 0 ◦C either. The only reaction condition that led to the formation of the desired product 15 in accept- able yields was by using diethyl ether as solvent at a temperature of 0 ◦C. After quenching of the reaction and removal of the solvent, the crude product could easily be puriﬁed by washing with methanol.

Br Br Br Br N N n-BuLi N N

N N Et2O, 0 °C N N H H 14 15

Scheme 3.12: Synthesis of bis(4-ethynyl-3,5-dimethylpyrazol-1-yl)methane (15).

The successful synthesis was conﬁrmed by 1H NMR spectroscopy. The signals of the methyl groups are therein detected at 2.10 and 2.44 ppm. The protons of the ethynyl moieties are detected at 4.15 ppm and the protons of the methylene bridge appear at a chemical shift of 6.13 ppm. In the 13C NMR spectrum, the methyl groups are observed at 10.5 and 12.3 ppm. The methylene bridge is detected at 60.7 ppm and the carbon atoms of the pyrazole rings are assigned to the signals at 102.4, 144.2 and 151.1 ppm. The ethynyl moiety that has been introduced during the reaction can be found at 75.4 and 81.1 ppm. The presence of the terminal alkyne could also be observed in the IR spectrum of compound 15. There, the alkyne group shows a strong C-H stretch vibration at 3221 cm−1 and a -C≡C- stretch band at 2106 cm−1.

81 3 Results and Discussion

3.2.3 Attempted Synthesis of Bis(4-trimethylsilyl-ethynyl-3,5-dimethylpyrazol-1-yl)acetic acid (16)

In an attempt to use the aforementioned Corey-Fuchs reaction to obtain a corresponding N,N,O coordinating bis(pyrazol-1-yl)acetic acid from bis(4-(2,2-dibromovinyl)- 3,5-dimethylpyrazol-1-yl)methane (14), a one pot reaction pathway was evaluated. Therefore, the educt 14 was converted into the respective lithium acetylide by two equivalents of n-butyllithium as mentioned in section 3.2.2. The resulting mixture was charged with trimethylsilyl chloride to obtain the trimethylsilyl-ethynyl species in situ. After- wards, another equivalent of n-butyllithium was added and a dry stream of carbon dioxide was applied. Aqueous workup was supposed to subsequently release the free carboxylic acid.

Br Br Br Br N N N N H H 14

1. Trimethylsilyl chloride n-BuLi 2. CO2 Et2O, 0 °C 3. H2O

CO2H

N N TMS TMS N N

Scheme 3.13: Attempted Synthesis of Bis(4-trimethylsilyl-ethynyl-3,5-dimethylpyrazol- 1-yl)acetic acid (16).

However, no solid product could be obtained from this reaction, nor did NMR spectroscopy of the resulting brownish oil reveal any signals indicating a successful synthesis. In further attempts, the synthesis was altered. Using 15 as educt also led to decomposition. The same is true for the direct application of three equivalents of n-butyllithium from the beginning or alterations of the solvent to tetrahydrofuran or varying temperatures. It could potentially be impossible to selectively deprotonate this molecule due to the number of acidic protons. However, the initial reaction protocol was supposed to overcome this problem. Yet all of the attempted syntheses led to decomposition of the substrate.

82 3.2 4-Ethynyl Substituted Pyrazole Based Ligands

3.2.4 [CuI(bedmpzm)] (17)

To evaluate the coordination behavior of 15, a series of transition metal complexes thereof was synthesized. In a ﬁrst attempt copper(I) iodide was reacted with 15. After stirring of 15 with this metal salt at ambient conditions for 30 minutes, the resulting colorless complex [CuI(bedmpzm)] (17) precipitated from solution and could be collected by ﬁltration in a very good yield of 85 %.

N N CuI N N N N acetonitrile N N Cu 15 I 17

Scheme 3.14: Synthesis of [CuI(bedmpzm)] (17).

The formation of the complex 17 could be confirmed by the shift of the signal of the methyl groups next to the coordination site from 2.10 ppm in the pure ligand to 2.20 ppm in the metal complex in the 1H NMR spectrum. The other methyl groups on the contrary were only slightly shifted by 0.01 ppm to 2.45 ppm. The protons of the terminal acetylenes are detected at 4.20 ppm and the methylene bridge appears at 6.23 ppm. Due to the low solubility, it was impossible to obtain a 13C NMR spectrum. However, the complex 17 could be confirmed by elemental analysis. Apart from the complex monomer shown in scheme 3.14, a polymeric system would be thinkable as well. In such a structure, the coordinatively unsaturated copper(I) could be bonded side-on to the acetylene moieties of another complex molecule. Such a coordination mode would ultimately lead to a polymeric structure with the same elemental composition as the structure proposed above. However, in this case, an insoluble material has to been assumed, which was not the case. Furthermore, the ν(C≡C) band in the IR spectrum would be expected at 1900- 1960 cm−1 as reported in the case of hydrotris(3-mesitylpyrazolyl)borato-copper(I) alkyne complexes.[191] Instead, the corresponding vibration was found at 2112 cm−1, which is very close to the free ligand (15) with 2106 cm−1. These findings strongly argue for the formation of the monomeric complex [CuI(bedmpzm)] (17) with no side-on coordination to the acetylene moieties as depicted in scheme 3.14.

83 3 Results and Discussion

3.2.5 [ZnCl2(bedmpzm)] (18)

In a similar fashion, the colorless [ZnCl2(bedmpzm)] (18) complex could be obtained. Once again, acetonitrile was used as solvent and the product precipitated within one hour after the addition of zinc(II) chloride to the ligand solution and could be collected via ﬁltration. Also for this compound, the yields were quite high with 79 % referring to bedmpzm (18).

N N ZnCl2 N N N N acetonitrile N N Zn 15 Cl Cl 18

Scheme 3.15: Synthesis of [ZnCl2(bedmpzm)] (18).

In the 1H NMR spectrum of compound 18, the methyl groups are detected at 2.10 and 2.44 ppm. The protons of the acetylene moieties can be found at 4.15 ppm and the methylene bridge has a chemical shift of 6.14 ppm. As for the copper(I) complex, a 13C NMR spectrum could not be obtained due to the low solubility of the complex. However, elemental analysis conﬁrmed the desired zinc(II) complex. As observed for the corresponding copper(I) complex [CuI(bedmpzm)] (17), the ν(C≡C) vibration was only shifted slightly in comparison to the free ligand 15 from 2106 cm−1 to 2110 cm−1, arguing against any side-on interaction of metal ions with the acetylene moieties.

3.2.6 [MnCl2(bedmpzm)2] (19)

A third transition metal complex of 15 that was synthesized was [MnCl2(bedmpzm)2](19). To do so, equimolar amounts of manganese(II) chloride and 58 were dissolved in acetonitrile and the resulting solution was stirred for one hour. Once again, the product precipitated during this time and the resulting colorless powder was collected via ﬁltration in yields of 82 %. In contrast to the previously reported complexes of bedmpzm (15), the reaction led to the formation of a bisligand complex with two equivalents of 15 bonded to the manganese(II) center. Unfortunately, it was impossible to record any NMR spectra, since the compound proofed insoluble in common solvents. However, due to their paramagnetic nature, they would have been of limited value.

84 3.2 4-Ethynyl Substituted Pyrazole Based Ligands

N N N N

N N MnCl2 2 Cl Mn Cl N N acetonitrile

15 N N N N

Scheme 3.16: Synthesis of [MnCl2(bedmpzm)2](19).

Nevertheless it was possible to conﬁrm the composition of [MnCl2(bedmpzm)2](19) via elemental analysis hinting at the proposed structure, as it is depicted in scheme 3.16. The IR spectrum once again shows no interaction of the metal ions with the acetylene moieties since the ν(C≡C) vibrational band remains almost unchanged at 2105 cm−1.

3.2.7 [CoCl2(bedmpzm)] (20)

A cobalt(II) chloride complex of bedmpzm (15) could be obtained by the same procedure as before. Yet precipitation of the deep blue complex took 24 hours. After this time, the product could be collected by ﬁltration and was obtained in yields of 80 %.

N N CoCl2 N N N N acetonitrile N N Co 15 Cl Cl 20

Scheme 3.17: Synthesis of [CoCl2(bedmpzm)] (20).

As for the mangenese(II) complexe (19), no NMR spectra could be recorded for [CoCl2- (bedmpzm)] (20), since the complex was insoluble in common organic solvents. However, due to their paramagnetic nature, they would have been of limited value. The composition of the complex however could be conﬁrmed by elemental analysis. Once again, the ν(C≡C) vibration was only shifted slightly in comparison to the free ligand 15 from 2106 cm−1 to 2114 cm−1, arguing against any side-on interaction of metal ions with the acetylene moieties.

85 3 Results and Discussion

3.2.8 [MoO2Cl2(bedmpzm)] (21) In order to prepare a molybdenum(VI) complex of bedmpzm (15), molybdenum(VI) dichloride dioxide was at ﬁrst dissolved in dry tetrahydrofuran to obtain the solvent stabilized [MoO2Cl2(THF)2]. To the resulting solution was added a solution of bedmpzm (15). The product could be collected by ﬁltration of the precipitate. A yield of 77 % regarding bedmpzm (15) could be obtained.

N N [MoO2Cl2] N N N N THF N N O Mo O 15 Cl Cl 21

Scheme 3.18: Synthesis of [MoO2Cl2(bedmpzm)] (21).

In contrast to the other transition metal complexes of bedmpzm (15) presented above, 21 was reasonably well soluble. Thus 1H NMR as well as 13C NMR spectra could be measured. In the 1H NMR spectrum, the methyl groups are detected at 2.10 and 2.44 ppm. The protons of the acetylene moieties appear with a chemical shift of 4.15 ppm and the protons of the methylene bridge can be found at 6.14 ppm. The 13C NMR spectrum on the other hand shows the methyl groups at 10.1 and 12.1 ppm. The carbon atom of the methylene bridge is assigned to the signal at 59.5 ppm. At 75.4 and 84.1 ppm follow the signals of the carbon atoms of the acetylene moieties. The signals at 101.2, 143.9 and 149.9 ppm derive from the pyrazole rings. The composition of this complex could as well be conﬁrmed by elemental analysis. Also for this complex, the IR spectrum revealed no interaction of the molybdenum ions with the acetylene moieties. The ν(C≡C) vibration was only shifted slightly in comparison to the free ligand 15 from 2106 cm−1 to 2118 cm−1. Furthermore, the ν(Mo=O) −1 −1 vibrational bands are found at νsym = 948 cm and νasym = 919 cm , which are in good agreement with the ﬁndings for the corresponding vinyl substituted complex −1 −1 [MoO2Cl2(bdmvpzm)] (3, νsym = 944 cm , νasym = 917 cm , see chapter 3.1.3).

86 3.2 4-Ethynyl Substituted Pyrazole Based Ligands

3.2.9 4-Iodopyrazole (22) and 4-Iodo-3,5-dimethylpyrazole (23)[192]

Since the initial aim to obtain an N,N,O coordinating 4-ethynylpyrazole based ligand failed on the route presented above, another synthetic pathway was attempted. Thus it was decided to attach the ethynyl substituents to the pyrazoles ﬁrst and then build up chelate or scorpionate ligands with ethynyl linkers starting from these educts.

[NH4]2[Ce(NO3)6], NH I NH 2 I N N 22

[NH4]2[Ce(NO3)6], NH I NH 2 I N N

Scheme 3.19: Synthesis of 4-iodopyrazole (22) and 4-iodo-3,5-dimethylpyrazole (23).[192]

The synthetic pathway that was chosen, was to carry out an Sonogashira reaction with 4-iodopyrazoles. To obtain these, pyrazole, respectively 3,5-dimethylpyrazole had to be iodinated ﬁrst. This was done in an electrophilic aromatic substitution reaction. The pyrazoles were therefore dissolved in acetonitrile and reacted with elemental iodine in the presence of ceric ammonium nitrate, as it is depicted in scheme 3.19. 4-iodo-3,5- dimethylpyrazole (23) could be obtained in yields of 69 % and 4-iodopyrazole (22) in yields of 83 %. The spectroscopic data agreed with the literature values.[192]

3.2.10 4-Iodo-1-tritylpyrazole (24)[77] and 4-Iodo-3,5-dimethyl-1-tritylpyrazole (25)[71]

In order to avoid undesired side reactions, especially electrophilic substitutions, a protection group was introduced. Therefore, triphenylmethylchloride (TrtCl) was applied after the deprotonation of the pyrazoles 22 and 23 with sodium hydride (see scheme 3.20). 4-Iodo-1-tritylpyrazol (24) could be obtained in yields of 85 % and 4-Iodo-3,5-dimethyl- 1-tritylpyrazole (25) in yields of 41 %. The obtained spectroscopic data agreed with the literature values.[71,77] The 1H NMR spectrum exhibits the signals of the methyl groups of compound 25 at 1.58 and 2.23 ppm. The pyrazole protons of compound 25 are detected at 7.43 and 7.69 ppm. A comparison of the signals of the trityl protecting group shows that they are

87 3 Results and Discussion

NaH NH TrtCl N I I N - NaCl N 22 24

NaH NH TrtCl N I I N - NaCl N

23 25

Scheme 3.20: Synthesis of 4-iodo-1-tritylpyrazol (24)[77] and 4-iodo-3,5-dimethyl-1- tritylpyrazole (25).[71] shifted downﬁeld in the spectrum of the unsubstituted 24 at 7.34 and 7.43 ppm, while the corresponding signals of 25 are observed at 7.10 and 7.27 ppm. In the 13C NMR spectrum of the dimethyl substituted 25, the methyl groups are assigned to the signals at 14.6 and 15.7 ppm. The carbon atoms of the pyrazole rings are detected at 66.9, 142.5 and 147.5 ppm. The remaining signals at 78.9, 127.3, 127.5, 130.3 and 142.9 ppm were assigned to the trityl protecting group. The spectrum of 24 is similar and contains the signals of the pyrazole carbon atoms at 55.6, 136.4 and 144.7 ppm. The trityl protecting group is observed at chemical shifts of 79.3. 127.8. 127.9. 130.1 and 142.7 ppm.

3.2.11 3,5-Dimethyl-4-(trimethylsilyl)ethynyl-1-tritylpyrazole (26)

As a precursor for the synthesis of 4-ethynyl substituted bis(pyrazol-1-yl)methane ligands, 26 was synthesized in a Sonogashira reaction from 3,5-dimethyl-4-iodo-1-tritylpyrazole (23) and trimethylsilyl acetylene to introduce the desired triple bond in position 4 of the pyrazole ring. The reaction was carried out in a mixture of dimethylformamide and triethylamine at 60 ◦C in a sealed flask to avoid premature evaporation of the volatile acetylene precursor. Similar reactions have been reported before, using different protecting groups.[183,193] After completion of the reaction, the product was purified via column chromatography and could be obtained in yields of 71 % referring to 23.

88 3.2 4-Ethynyl Substituted Pyrazole Based Ligands

[PdCl2(PPh3)2] N CuI, TMS-acetylene N I Si N DMF, NEt3, 60 °C N

25 26

Scheme 3.21: Synthesis of 3,5-dimethyl-4-(trimethylsilyl)ethynyl-1-tritylpyrazole (26).

The trimethylsilyl group can be found in the 1H NMR spectrum with a chemical shift of 0.23 ppm, thus conﬁrming successful product formation. The methyl groups result in signals at 1.57 and 2.26 ppm. The trityl protection group is assigned to two multiplets at 6.85-6.95 and 7.00-7.10 ppm. The successful substitution of the iodine can also be observed in the 13C NMR spectrum, in which the newly introduced trimethylsilyl groups cause a signal at 0.23 ppm. The methyl groups at the pyrazole ring are found at 12.9 and 13.9 ppm. The carbon atoms of the triple bond are assigned to the signals at 97.9 and 98.1 ppm. The tertiary carbon atom of the trityl group has a chemical shift of 78.6 ppm while the carbon atoms of the phenyl rings rise signals at 127.3, 127.5, 130.3 and 142.8 ppm. Finally, the pyrazole ring was detected at 104.4, 145.4 and 148.1 ppm.

3.2.12 4-(Trimethylsilyl)ethynyl-1-tritylpyrazole (27)

Similar to the synthesis of 26, it was possible to obtain the unsubstituted 4-((trimethylsilyl)ethynyl)-1-tritylpyrazole (27) via a Sonogashira reaction from 4-iodo-1-tritylpyrazole (24) and trimethylsilyl acetylene. After puriﬁcation via column chromatography, the compound could be obtained in yields of 68 %.

[PdCl2(PPh3)2] N CuI, TMS-acetylene N I Si N DMF, NEt3, 60 °C N 24 27

Scheme 3.22: Synthesis of 4-(trimethylsilyl)ethynyl-1-tritylpyrazole (27).

The 1H NMR spectrum of compound 27 exhibits the signal of the protecting trimethylsilyl group at 0.21 ppm. The trityl group appears as a multiplet at a chemical shift of 7.29 ppm.

89 3 Results and Discussion

The remaining signals at 7.56 and 7.77 ppm can be assigned to the protons of the pyrazole ring. The 13C NMR spectrum is also very similar to the spectrum of compound 26. However, the TMS group is shifted upﬁeld considerably to a chemical shift of −0.06 ppm. The same could be observed for the carbon atoms of the triple bond, which could be detected with an upﬁeld shift of about 3 ppm at 95.1 and 96.5 ppm, respectively.

3.2.13 3,5-Dimethyl-4-(trimethylsilyl)ethynylpyrazole (28)

The next step on the way to pyrazole based scorpionate ligands bearing acetylene moieties was the synthesis of an ethynyl substituted derivative of 3,5-dimethylpyrazole.

N CF3COOH NH Si Si N CH2Cl2 N

26 28

Scheme 3.23: Initial synthesis of 3,5-dimethyl-4-(trimethylsilyl)ethynylpyrazole (28).

Therefore, the trityl protected species 3,5-dimethyl-4-(trimethylsilylethynyl)-1-tritylpyrazole (26) (see section 3.2.11) was deprotected with triﬂuoroacetic acid in dichloromethane (see scheme 3.23). After puriﬁcation via column chromatography, the product could be obtained in yields of 41 %. However, under these conditions the protection group proofed to be unnecessary for the Sonogashira reaction, that is applied to obtain this product, so a more straight forward synthesis was employed.

[PdCl2(PPh3)2] NH CuI, TMS-acetylene NH I Si N DMF, NEt3, 60 °C N

23 28

Scheme 3.24: Final synthesis of 3,5-dimethyl-4-(trimethylsilyl)ethynylpyrazole (28).

An alternative pathway via a Sonogashira reaction with trimethylsilylacetylene and 3,5- dimethyl-4-iodopyrazole (23) also resulted in 3,5-dimethyl-4-(trimethylsilyl)ethynylpyrazole (28). Complete turnover could only be achieved, if dimethylformamide was employed

90 3.2 4-Ethynyl Substituted Pyrazole Based Ligands as a solvent. Reactions in tetrahydrofuran and triethylamine led to incomplete reactions (see scheme 3.24). Both pathways led to identical products. After puriﬁcation via column chromatography, the product 28 could be obtained in yields of 71 % referring to 4-iodo-3,5-dimethyl-1- tritylpyrazole (25).

H N N Si Si N N H

Figure 3.8: Cyclic dimer structure of 3,5-dimethyl-4-(trimethylsilyl)ethynylpyrazole (28).[194]

The 1H NMR spectrum of compound 28 shows the signal of the trimethysilyl group at 0.24 ppm, thus confirming the successful substitution of the iodine. The methyl groups are detected at 2.31 ppm. These protons do not split in two singlets, as it would be expected, since the pyrazoles form symmetric dimeric structures via hydrogen bonds as depicted in figure 3.8.[194] The proton of the secondary amine is assigned to a signal at 10.45 ppm. The formation of the product could also be verified via 13C NMR spectroscopy, with the newly introduced trimethylsilyl group at 0.21 ppm. The methyl groups at the pyrazole ring are detected at 11.3 ppm. The sp hybridized carbon atoms are observed at 97.0 and 97.7 ppm. The pyrazole carbon atom in position 4 to which they are bonded is detected at 101.5 ppm. The remaining pyrazole carbon atoms can be found at 147.2 ppm.

3.2.14 2,2-Bis(4-ethynyl-3,5-dimethylpyrazol-1-yl)acetic acid (29)

With a suitable ethynyl substituted pyrazole precursor at hand, a first bis(pyrazolyl)acetic acid derivative could be synthesized. The one pot synthesis by Burzlaff et al. was applied.[11] Therefore, the pyrazole was reacted with dibromoacetic acid under basic conditions in the presence of a phase transfer catalyst, as depicted in scheme 3.25. After acidic workup, compound 29 could be obtained as yellowish powder by filtration. Due to the basic conditions used during the phase transfer reaction, the trimethylsilyl protecting groups were removed during the process, thus rendering a further deprotection step moot. The 1H NMR spectrum of 29 showed the signals of the methyl groups at 2.23 and 2.35 ppm. The existence of the signal of acetylenic protons at 3.19 ppm in combination with the missing signal of the trimethylsilyl group confirmed the deprotection during the phase transfer reaction. Furthermore, the proton at the bridging carbon atom was

91 3 Results and Discussion

HO O 1. Br2CHCO2H, KOH, K2CO3, BTEAC NH 2. HCl N N 2 Si N THF N N

28 29

Scheme 3.25: Synthesis of 2,2-bis(4-ethynyl-3,5-dimethylpyrazol-1-yl)acetic acid (29). detected at a chemical shift of 6.82 ppm. The remaining resonance at 9.86 ppm could be assigned to the acidic proton of the carboxylate function. Furthermore, the compound could also be confirmed via 13C NMR spectroscopy. In the corresponding spectrum, the methyl groups were found at chemical shifts of 10.6 and 12.4 ppm, respectively. The resonance of the bridging carbon atom was observed at 81.6 ppm. The carbon atoms of the ethynyl moiety were detected at 103.3 and 124.8 ppm. The signals at 144.7, 146.7 and 151.4 ppm could be assigned to the carbon atoms of the pyrazole rings. The last signal at 166.0 ppm was caused by the carbon atom of the carboxylate moiety. Despite the fact that it was possible to confirm the compound via mass spectrometry, the elemental analysis showed impurities, which could not be removed. While the original bis(3,5-dimethylpyrazol-1-yl)acetic acid can be purified by recrystallization from acetone, the additional ethynyl substituents drastically improved the solubility of compound 29, making such procedures ineffective.

3.2.15 (2-Hydroxyphenyl)-bis(3,5-dimethyl-4-(trimethylsilyl)- ethynylpyrazol-1-yl)methane [HOPhbdmeTMSpzm] (30)

Starting from 3,5-dimethyl-4-(trimethylsilyl)ethynylpyrazole (28) it was now also possible to obtain a first bis(pyrazol-1-yl)methane based heteroscorpionate ligand. For the synthesis, the well established one pot synthesis of Elflein et al. was employed, that was already mentioned in section 1.1.3.[23] In a first attempt compound 28 was deprotonated with sodium hydride prior to reacting it with thionyl chloride, to obtain a S=O bridged species in situ. Without further purification, salicylaldehyde and one equivalent of pyridine were added to the reaction mixture, to obtain the desired ligand (2-hydroxyphenyl)-bis(3,5-dimethyl-4-(trimethylsilyl)-ethynylpyrazol-1-yl)methane [HOPhbdmeTMSpzm] (30) (see scheme 3.26). After purification via column chromatography, 30 could be obtained in yields of 45 % referring to 3,5-dimethyl-4-(trimethylsilyl)ethynylpyrazole (28). The 1H NMR spectrum of compound 30 shows the protons of the trimethylsilyl groups

92 3.2 4-Ethynyl Substituted Pyrazole Based Ligands

O NaH, S NH SOCl N N 2 Si 2 Si Si N THF, N N 0 °C 28

H O , pyridine N N Si Si - SO2 N N 30

Scheme 3.26: Synthesis of (2-hydroxyphenyl)-bis(3,5-dimethyl-4-(trimethylsilyl)ethynylpyrazol-1-yl)methane [HOPhbdmeTMSpzm] (30). at 0.23 ppm. The successful ligand formation is backed by the splitting of the methyl signal. The signals appear in the spectrum at 2.14 and 2.23 ppm, respectively. The signals of the aromatic protons are detected as a multiplet at 6.79 ppm and a triplet 3 with a coupling constant of J H,H = 7.21 Hz at 7.15 ppm. Furthermore, the formation of the desired compound is proved by the methine signal at 7.40 ppm. More downfield at 9.03 ppm appears the broad signal of an acidic proton, which can be assigned to the phenolic hydroxyl group. The desired N,N,O coordinating ligand could also be confirmed by 13C NMR spectroscopy. The signals of the the trimethylsilyl groups are therein shown at 0.15 ppm, followed by the methyl groups of the pyrazole moieties at 10.6 and 12.6 ppm. The methine carbon atom is detected at 72.9 ppm. Further downfield the carbon atoms of the ethynyl moieties are assigned to the signals at 96.4 and 98.8 ppm. The pyrazole ring exhibits signals at 104.0 ppm for the carbon atom in position 4 and 143.7 ppm respectively 150.8 ppm for the positions 3 and 5. Furthermore, the carbon atoms of the phenoxy moiety have appeared at 117.8, 120.0, 121.1, 129.2, 131.0 and 154.8 ppm.

TMS 3.2.16 [MoO2Cl2(HOPhbdme pzm)] (31)

After the successful synthesis of ligand 30, it was attempted to obtain a ﬁrst transition metal complex thereof. With molybdenum dichloride dioxide, a molybdenum(VI) metal fragment was chosen. In accordance with the synthesis for similar compounds by San- tos et al., this salt was ﬁrst dissolved in tetrahydrofuran to form the solvent stabilized [149] [MoO2Cl2(THF)2]. After the addition of ligand 30, the so far colorless solution turned

93 3 Results and Discussion yellow and subsequent treatment with n-hexane led to the precipitation of the yellow TMS 3 [MoO2Cl2(HOPhbdme pzm)] (31) complex. The desired κ coordination could however not be achieved by this route, although similar complexes with a menthopyrazole based ligand exhibited N,N,O coordination without the addition of base to the reaction mixture.[195]

N N Si Si N N

[MoO2Cl2(THF)2]

N N Si Cl Si N N Mo O O Cl 31

TMS Scheme 3.27: Synthesis of [MoO2Cl2(HOPhbdme pzm)] (31).

In general, two isomers of this complex would be possible. On the one hand, the two chlorido ligands could be in cis position to each other. On the other hand, it would be possible for them to be in trans position. The later possibility is depicted in scheme 3.27 as the ﬁrst option would lead to an asymmetric complex, resulting in two sets of signals in the NMR spectra. This was however not observed. Therefore, the exclusive formation of the symmetric trans isomer is assumed. Thus, the methyl groups of the pyrazole rings only result in two instead of four signals at 2.55 and 2.75 ppm in the 1H NMR spectrum. Also, the trimethyl silyl groups do not split up and are detected at 0.23 ppm. The signals of the aryl protons can be observed 3 at 6.86 ppm as a triplet with a coupling constant of J H,H = 7.5 Hz and as a second 3 triplet at 6.93 ppm with J H,H = 4.5 Hz. The remaining two aryl protons split up each

94 3.2 4-Ethynyl Substituted Pyrazole Based Ligands

3 into doublets, one at 7.10 ppm with a coupling constant of J H,H = 9.0 Hz and one at 3 7.34 ppm with J H,H = 6.0 Hz. The remaining singlet at 7.30 ppm can be assigned to the proton of the methine bridge. The phenolic proton could not be observed. This is probably caused by deuterium exchange with traces of DCl in the solvent. The 13C NMR spectrum revealed only one set of signals as well. The trimethyl silyl group is therein detected at −0.05 ppm, which is a 0.20 ppm upfield shift in comparison to the pure ligand 30. The methyl groups on the other hand are barely influenced and lead to signals at 11.0 and 13.9 ppm, respectively. The bridging carbon atom has a chemical shift of 70.4 ppm. The signals at 93.8 and 100.9 ppm can be assigned to the acetylene groups. The pyrazole rings are found at chemical shifts of 106.3, 142.8 and 156.7 ppm. The carbon atoms of the aryl ring are detected at 120.6, 120.7, 121.8, 128.4 and 132.6 ppm. As expected, the carbon atom with the strongest downfield shift is the hydroxyl substituted one at 157.1 ppm. The successful incorporation of the molybdenum fragment could furthermore be confirmed via infrared spectroscopy. Therein, the stretching vibrations of the molybdenum oxygen −1 bonds are observable at νe = 941 (νsym) and 921 cm (νasym). Furthermore, the proposed κ2 coordinated complex is also backed by the elemental analysis. There, the carbon value differs by 1.05 %. If the ligand was κ3 coordinated, the difference amounts to 3.69 %, since one chloride atom would have to be abstracted in this case. For these reasons, the κ2 coordinated complex can be assumed.

3.2.17 (2-Hydroxyphenyl)-bis(3,5-dimethyl-4-ethynylpyrazol-1-yl)methane (32)

In order to enable ligand 30 to undergo cross coupling or Click reactions, it is necessary to remove the protecting trimethyl silyl groups. To show that this is easily possible, two different reaction conditions were evaluated. On the one hand, it was attempted to remove the protecting group by the addition of potassium fluoride in a mixture of methanol and tetrahydrofuran. On the other hand, potassium carbonate was used. Both routes led to the terminal alkyne with similar yields of around 80 % and can therefore be chosen, what can gain importance, if not a free ligand, but instead a complex is to be deprotected. The loss of the trimethyl silyl group can reliably be verified by the non existence of the corresponding signal in the 1H NMR spectrum of compound 32. The methyl groups are still found at 2.18 and 2.23 ppm. The additional proton of the terminal alkyne, which is a second evidence for the successful deprotection, is detected at 3.20 ppm. The methine proton is slightly shifted downfield to 7.45 ppm. The protons of the aryl ring split up in 3 a triplet at 7.15 ppm with a coupling constant of J H,H = 6.0 Hz. The remaining aryl

95 3 Results and Discussion

N N Si Si N N

K2CO3 or KF THF, MeOH

N N N N

Scheme 3.28: Synthesis of (2-hydroxyphenyl)-bis(3,5-dimethyl-4-ethynylpyrazol-1- yl)methane (32). protons result in a multiplet at 6.81 ppm. The 13C NMR spectrum also confirms the absence of the trimethyl silyl group. The most upfield signals in the spectrum are caused by the methyl groups at 10.5 and 12.5 ppm. The carbon atoms of the alkyne moiety are shifted upfield to 75.3 and 81.4 ppm in comparison to the protected species with 93.8 and 100.9 ppm. The shift of the pyrazole carbon atoms is only slightly altered. Their resonances can be found at 102.7, 144.1 and 150.9 ppm. The same is true for the aryl carbon atoms with chemical shifts between 120 and 130 ppm and 154.8 ppm for the hydroxyl substituted carbon atom. Furthermore, the compound could be verified via mass spectrometry. Therein is found as the deprotonated species [M-H]− with 100 % intensity at 343.165 m/z.

3.2.18 (1-Methylimidazol-2-yl)-bis(3,5-dimethyl-4-(trimethylsilyl)- ethynylpyrazol-1-yl)methane (33)

Ut was possible to obtain an N,N,N coordinating ligand by the same one pot synthesis as used for the synthesis of [HOPhbdmeTMSpzm] (30, see section 3.2.15). Therefore, the salicylaldehyde that was used for the synthesis of 30 was replaced by 1-methyl-2- imidazolecarboxaldehyde.

96 3.2 4-Ethynyl Substituted Pyrazole Based Ligands

After the deprotonation of 3,5-dimethyl-4-(trimethylsilyl)ethynylpyrazole (28) by sodium hydride, the pyrazolate was reacted with thionyl chloride was applied. After subsequent addition of 1-methyl-2-imidazolecarboxaldehyde and one equivalent of pyridine, the desired product (1-Methylimidazol-2-yl)-bis(3,5-dimethyl-4-(trimethylsilyl)ethynylpyrazol- 1-yl)methane (33) was formed and could be isolated via column chromatography. Compound 33 could be obtained in yields of 9 % referring to 3,5-dimethyl-4-((trimethylsilyl)ethynyl)pyrazole (28).

O NaH, S NH SOCl N N 2 Si 2 Si Si N THF, N N 0 °C 28

N N N N

H O , pyridine N N Si Si - SO2 N N 33

Scheme 3.29: Synthesis of (1-methylimidazol-2-yl)-bis(3,5-dimethyl-4-(trimethylsilyl)- ethynylpyrazol-1-yl)methane (33).

Product formation could be confirmed via 1H NMR spectroscopy. The signal at 0.22 ppm could be assigned to the trimethylsilyl groups. The methyl groups of the pyrazole rings could be detected at 2.17 and 2.23 ppm, respectively. The methyl group of the imidazole moiety is shifted upfield to 3.33 ppm in comparison to the educt spectrum, in which it is detected at 3.99 ppm. In the same way, the two protons of the imidazole ring are shifted 3 upfield and generate two doublets at 6.92 ppm and 7.04 ppm with J H,H = 3.0 Hz. The educt spectrum of 1-methyl-2-imidazolecarboxaldehyde shows these protons at 7.08 and 7.24 ppm. The last signal at 7.48 ppm could be assigned to the methine bridge. The 13C NMR spectrum verified the proposed structure as well. The trimethylsilyl groups could be detected at 0.14 ppm, followed by the methyl groups of the pyrazole rings at 10.7 and 12.6 ppm. The carbon atom of the methine bridge, that was formed during the reaction, shows a signal at 70.4 ppm. The acetylene carbon atoms have chemical shifts of 96.5 and 98.5 ppm. The pyrazole rings appear at chemical shifts of 104.7, 140.1 and 144.4 ppm. These results correlate, just as the values from the 1H NMR, well with the values found for compound 30 (see section 3.2.15), indicating that the different third donor

97 3 Results and Discussion group does only slightly inﬂuence the electronical structure of the pyrazole backbone of the ligand. Furthermore, the methyl group of the imidazole moiety is detected at 33.0 ppm and the carbon atoms of the imidazole ring can be found at 123.0, 128.2 and 150.8 ppm.

3.2.19 (1-Methylimidazol-2-yl)-bis(3,5-dimethyl-4-ethynylpyrazol-1- yl)methane (34)

As already shown for compound 32, it might be necessary to remove the protecting trimethylsilyl groups, in order to enable further reactions like Click or further Sono- gashira reactions with the acetylene residue. As stated in chapter 3.2.17, two different deprotection pathways were evaluated, which both succeeded in similar yields of almost 80 %. On the one hand, the deprotection was carried out using basic conditions. In this case, potassium carbonate was employed. On the other hand the reaction was carried out exploiting the high affinity of silyl moieties towards halides, especially fluoride.[196] In both cases, the reaction was carried out in a mixture of tetrahydrofuran and methanol.

N N

N N Si Si N N

K2CO3 or KF THF, MeOH

N N

N N N N

Scheme 3.30: Synthesis of (1-methylimidazol-2-yl)-bis(3,5-dimethyl-4-ethynylpyrazol-1- yl)methane (34).

The successful deprotection could be monitored via NMR spectroscopy. The 1H NMR spectrum of 34 shows no signal of the trimethyl silyl anymore. The signals of the methyl

98 3.2 4-Ethynyl Substituted Pyrazole Based Ligands substituents of the pyrazole rings are detected at 2.21 and 2.24 ppm, respectively. The proton of the terminal alkyne, a further proof for the performed desilylation, is found at a chemical shift of 3.19 ppm. The protons of the methyl group located at the imidazole moiety are detected at 3.34 ppm. The signals at 6.93 and 7.05 ppm can be assigned to the protons of the imidazole moiety. Most downfield at 7.54 ppm, the proton of the methine bridge is detected. Similarly, no trimethyl silyl resonance could be found in the 13C NMR spectrum of compound 34. Instead, the most upfield signals are the resonances of the methyl substituents of the pyrazole rings at 10.5 and 12.5 ppm. The methyl substituent of the imidazole moiety is detected at 30.0 ppm. The carbon atom of the methine bridge has a chemical shift of 70.2 ppm. The signals at 75.3 and 81.4 ppm could be assigned to the carbon atoms of the acetylene moiety. In comparison to the trimethyl silyl protected acetylene, these signals are shifted upfield by 20 ppm (compare 3.2.18). The carbon atoms of the imidazole ring are detected at 103.4, 140.0 and 144.7 ppm. The remaining signals at 123.1, 128.0 and 150.9 ppm could be assigned to the pyrazole rings.

99 3 Results and Discussion

3.2.20 Summary of 4-Ethynyl Substituted Pyrazole Based Ligands

In this chapter, it could be shown, that it is possible to obtain the corresponding chelate and heteroscorpionate ligands based on 3,5-dimethyl-4-(trimethylsilyl)ethynylpyrazole (28) in the established one pot syntheses.[11,23] The ligands that could be synthesized by various protocols are depicted in scheme 3.31.

HO O

N N N N N N N N

15 29

HN TMS N

28 N N OH

N N N N N N N N

34 32

Scheme 3.31: 4-Ethynylpyrazole based scorpionate ligands.

The implementation of the acetylene moieties allows for a range of reactions to further modify the ligands or their complexes. Among these reactions are Glaser, Cadiot- Chodkiewicz or Sonogashira coupling reactions as well as the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC). The possible applications are manifold. In chapter 3.4, model ligands for Rieske dioxygenases will be presented, that are based on these principles. Furthermore, the introduction of ﬂuorophores, which could be switched via paramagnetic ﬂuorescence quenching, induced by metal centers coordinated to the ligand, could be an interesting opportunity. Besides, these linkers could serve as an easy way to PEGylate such ligands, thus im- proving the solubility of the resulting compounds via polyethylene glycol polymer (PEG) chains attached to the linker groups, which is a common procedure in pharmaceutical chemistry.[197]

100 3.3 Coordination Polymers of 1,4-Bis(1H-pyrazol-4-yl)butadiynes

3.3 Coordination Polymers of 1,4-Bis(1H-pyrazol-4-yl)- butadiynes

So far, 4-ethynyl substituted pyrazoles were used to obtain ligands by connecting two equivalents via methylene and methine bridges. Yet, the ethynyl moieties enable these precursors to undergo homo coupling reactions. Starting from the trityl protected 4- ethynyl substituted pyrazoles discussed above (see chapter 3.2), ligands suitable for 1D coordination polymers should be obtainable via such coupling reactions. A related compound could be obtained by T. Waidmann by performing a Glaser coupling reaction with a similarly substituted imidazole derivative.[170] The resulting ligand is depicted in ﬁgure 3.9.

N N

Figure 3.9: Structure of bis(N-methylimidazol-2-yl)butadiyne (bmib) according to T. Waidmann.[170]

Thus, corresponding compounds based on pyrazole derivatives should be synthesized in this part of this thesis. As already discussed above (see chapter 1.6.3), Navarro and coworkers could already succeed in the preparation of ﬁrst MOFs based on such ligands. For their experiments, they used the Boc protected ligands depicted in ﬁgure 3.10, which were deprotected in situ during the complexation with metal fragments.[180–182]

O R R

O N N N N O

R R O R = H / CH3

Figure 3.10: Structures of 1,4-bis[1-Boc-pyrazol-4-yl]butadiyne and 1,4-bis[1-Boc-3,5- [180–182] dimethylpyrazol-4-yl]butadiyne (Boc2L).

However, Navarro and coworkers did not isolate the unprotected ligand and could therefore neither study its properties nor obtain coordination polymers based on the neutral 1,4-bis(3,5-dimethyl-1H -pyrazol-4-yl)butadiyne ligand. Therefore, the synthesis using the trityl protecting group instead of the Boc protecting group and the properties of 1,4-bis(1H -pyrazol-4-yl)butadiynes as well as their abilities to form coordination polymers will be discussed in the following chapter.

101 3 Results and Discussion

3.3.1 3,5-Dimethyl-4-ethynyl-1-tritylpyrazole (35)

To synthesize the Glaser coupling product of 4-ethynyl-3,5-dimethylpyrazole, it was necessary to avoid premature coordination of the pyrazole to the metal catalyst, that is used during this procedure. Therefore, trityl, a bulky protecting group, was employed to shield the nitrogen donor functions of the resulting ligand. For this reason, the synthesis was started from 3,5-dimethyl-4-((trimethylsilyl)ethynyl)- 1-tritylpyrazole (26, see chapter 3.2.11). In the ﬁrst step, the trimethylsilyl group, which protects the terminal alkyne function had to be removed, in order to make Glaser type coupling reactions possible. Therefore, 26 was treated with potassium carbonate in a mixture of tetrahydrofuran and methanol, to obtain the desired terminal alkyne species in high yields. The crude product was washed with water and afterwards used without further puriﬁcation.

N K2CO3 N Si N THF/MeOH N

26 35

Scheme 3.32: Synthesis of 3,5-dimethyl-4-ethynyl-1-tritylpyrazole (35).

The successful deprotection of the alkyne function was confirmed via NMR spectroscopy. In comparison to 26, the trimethylsilyl signal in the 1H NMR spectrum disappeared. The protons of the methyl group are shifted upfield to 1.37 and 2.06 ppm, respectively. The hydrogen atom of the terminal alkyne can be found at 3.02 ppm. More downfield in the aromatic region, the resonances of the trityl group were observed as a multiplet at 6.99 ppm. These findings could also be confirmed via 13C NMR spectroscopy. No signals resulting from trimethylsilyl groups could be found therein. The methyl substituents are detected at 12.9 and 13.8 ppm, respectively. The carbon atoms of the triple bond exhibit an upfield shift from 97.9 and 98.1 ppm to 78.5 and 81.2 ppm. The signals of the pyrazole ring are found at 103.3, 145.6 and 148.1 ppm. The trityl protecting group was detected at chemical shifts of 127.3, 127.5, 130.3 and 142.8 ppm.

102 3.3 Coordination Polymers of 1,4-Bis(1H-pyrazol-4-yl)butadiynes

3.3.2 1,4-Bis(3,5-dimethyl-1-tritylpyrazole-4-yl)butadiyne (36)

After the removal of the trimethylsilyl protecting group, the terminal alkyne could now be reacted in a Glaser type homo coupling reaction. In order to increase yields, an Eglinton coupling reaction was used. The original Glaser protocol uses a catalytic amount of a copper(I) salt, which is oxidized by oxygen to the active catalytic copper(II) species. During the coupling step, the copper(II) ions get reduced and are reoxidized by oxygen again.[198] The Eglinton coupling however uses stoichiometric amounts of a copper(II) salt, e.g. copper(II)acetate to promote the reaction. In both cases, pyridine is used as base to deprotonate the terminal alkyne.[199] The reaction goes to completion without the observation of any side products and could therefore be puriﬁed by thorough washing with water to remove the metal salts.

2 N N

Cu(OAc)2 MeCN/pyridine

N N N N

Scheme 3.33: Synthesis of 1,4-bis(3,5-dimethyl-1-tritylpyrazole-4-yl)butadiyne (36).

The success of the coupling reaction was conﬁrmed by NMR spectroscopy. The 1H NMR spectrum of the resulting compound contains two singlets at 1.57 and 2.25 ppm, originat- ing from the two methyl substituents of the pyrazole rings. Furthermore, two multiplets at 7.11 and 7.29 ppm represent the trityl protecting groups. No signal of an acetylene proton could be observed anymore. Furthermore, the 13C NMR spectrum reveals the methyl substituents of the pyrazole rings

103 3 Results and Discussion at chemical shifts of 13.2 and 14.4 ppm. The signals at 74.8 and 79.3 ppm can be assigned to the four carbon atoms of the butadiyne bridge. This is a strong sign for the successful coupling reaction, since those carbon atoms experienced a strong upﬁeld shift of around 20 ppm in comparison to the spectra of the trimethyl silyl protected precursor (see chapter 3.2.11) and the terminal alkyne species (see chapter 3.3.1). The remaining signals of the pyrazole rings at 104.0, 147.4 and 149.3 ppm and of the trityl protecting groups at 127.9, 128.1, 130.8 and 143.2 ppm persist almost unchanged.

3.3.3 1,4-Bis(3,5-dimethyl-1H-pyrazol-4-yl)butadiyne (37)

In the last step of the ligand synthesis, the trityl protecting group needs to be removed. This bulky group prevented the nitrogen donor functions of the ligand from polymerization with the metal ions involved in the Eglinton coupling reaction shown above (chapter 3.3.2).

N N N N

CF3CO2H CH2Cl2

HN NH N N

Scheme 3.34: Synthesis of 1,4-bis(3,5-dimethyl-1H-pyrazol-4-yl)butadiyne (37).

The deprotection of the pyrazole moieties can be performed under mild conditions. A stoichiometric amount of triﬂuoroacetic acid in dichloromethane leads to the formation of the unprotected product. This product is capable of forming a polymer structure of its own, as it is depicted in ﬁgure 3.11. This might explain its low solubility in unpolar solvents. These polymer strands can only be cleaved by polar or even better by protic solvents, that are capable to form hydrogen bridges on their own, for example methanol.

104 3.3 Coordination Polymers of 1,4-Bis(1H-pyrazol-4-yl)butadiynes

H H N N N N N N N N H H n

Figure 3.11: Polymer structure of 1,4-bis(3,5-dimethyl-1H-pyrazol-4-yl)butadiyne (37).

Since this is not the case for dichloromethane, in which the reaction is carried out, the desired product precipitates directly from solution upon its formation and can be collected via filtration. The crude product was washed with organic solvents of lower polarity to obtain it in its pure form. The obtained compound was examined via NMR spectroscopy. The methyl substituents of the pyrazole rings split in the 1H NMR spectrum into two singlets, depending on the solvent. Whereas deuterated acetone only leads to one singlet at 2.28 ppm, deuterated dimethyl sulfoxide leads to a splitting into two singlets at 2.17 and 2.25 ppm. Further- more, it was possible to detect the signal of the pyrazole NH at 12.6 ppm. This behavior most likely relates to the ability of dimethyl sulfoxide molecules to bond to the ligand via hydrogen bridges. While the compound is a hydrogen bond acceptor due to its un- protonated nitrogen atom, it can act as a hydrogen bond donor as well via its second, protonated nitrogen donor, as it is depicted in figure 3.11. 13C NMR spectroscopy could only be performed in dimethyl sulfoxide, since the required concentration could not be reached in acetone. As observed in the 1H NMR, the methyl groups split up into two signals at 10.0 and 12.5 ppm. The carbon atoms of the butadiyne bridge are detected at 97.5 and 98.3 ppm. Furthermore, the signals at 105.5, 144.1 and 150.7 ppm can be assigned to the carbon atoms of the pyrazole rings. Crystals suitable for an X-ray structure determination could be obtained by layering a solution of 37 in methanol with n-hexane. The crystal structure contains two molecules of 1,4-bis(3,5-dimethyl-1H -pyrazol-4-yl)butadiyne (37) and one water molecule in the asymmetric unit. The compound crystallized in the monoclinic space group P 21/c. Selected bond lengths and angles are listed in table 3.9. As can be seen in figures 3.13 and 3.12, the two different molecules mostly differ in the angle of the butadiyne linker. The angles 6 (C4-C3A-C3B) and 6 (C3A-C4-C23) of the linear species amount to 179.70(20)◦ and 176.81(18)◦ and result in an almost linear conformation. The corresponding angles of the bent molecule on the other hand differ more from the ideal 180◦ angles with 6 (C1-C2A-C2B) = 176.37(12)◦ and 6 (C2A-C1-C13) = 174.97(18)◦. While this may seem like a minor difference, the significance can be easily seen in figure 3.12, which provides a side view on the packing motif. Therein, the linear molecules are colored blue, while the bent species is depicted in yellow. Furthermore, the

105 3 Results and Discussion

Figure 3.12: Packing motif of 37 (blue: linear molecule, yellow: bent molecule). Thermal ellipsoids are drawn at the 50 % probability level. Hydrogen atoms have been omitted for clarity. butadiyne linkers of both molecules contain discrete triple (in both cases 1.202(2) Å) and single bonds (1.377(3) Å and 1.375(3) Å) which show no sign of conjugation.[200] As can also be seen in ﬁgure 3.12, the two diﬀerent species are arranged in alternating layers. The pyrazole rings show parallel-displaced π − π stacking. The distance between the pyrazole rings amounts to 3.5330(21) Å. The linear molecules connect two layers of

Distances (Å) bent molecule linear molecule C1-C2A 1.202(2) C3A-C4 1.202(2) C2A-C2B 1.377(3) C3A-C3B 1.375(3) C1-C13 1.419(2) C4-C23 1.420(2) C13-C14 1.402(2) C23-C24 1.403(2) N11-N12 1.362(2) N21-N22 1.366(2) N11-O1 2.9097(14) N21-O1 2.9082(18) N12-N22 2.8848(19) N21-N11 4.2482(20)

Angles (deg) bent molecule linear molecule C1-C2A-C2B 176.37(12) C4-C3A-C3B 179.70(20) C2A-C1-C13 174.97(18) C3A-C4-C23 176.81(18) N11-N12-C14 109.25(13) N21-N22-C24 108.82(13) N11-N12-N22 120.249(104) N21-N22-N12 119.247(104)

Table 3.9: Selected interatomic distances (Å) and angles (deg) for both molecules in the asymmetric unit of compound 37.

106 3.3 Coordination Polymers of 1,4-Bis(1H-pyrazol-4-yl)butadiynes the bent species via hydrogen bridges. Each molecule of the latter is connected to only one of the neighboring layers via hydrogen bridges to one of the linear molecules, as it is depicted in ﬁgure 3.13. Apart from π stacking, these hydrogen bridges seem to be the driving force behind the curving of the butadiyne bridge of the bent species. This curvature is necessary to align with the pyrazole moiety of the next linear molecule as well as with the central water molecule in such a way, that hydrogen bonding becomes possible. This leads to a structure, in which the oxygen atom of the water molecule is surrounded tetrahedrally by four ligand molecules. This is done via hydrogen bridges. These bridges seem to exist on the hand between O1 and N11 as well as between O1 and N21. The corresponding distances amount to 2.9097(14) Å and 2.9082(18) Å, respectively, which is very well within in the range of typical hydrogen bridges.[201]

Figure 3.13: Molecular structure of 37. Thermal ellipsoids are drawn at the 50 % probability level. Most hydrogen atoms have been omitted for clarity. Only one of the two disordered proton distributions is depicted.

The distance between the two bonding pyrazole moieties (N12-N22) is even smaller with 2.8848(19) Å, which also argues for the existence of a hydrogen bridge between them.[201] Summing it up, every second ligand molecule accepts one hydrogen bond from the water molecule and at the same time donates one hydrogen bond to its bonding partner. The partner itself then donates one hydrogen bond back to the water molecule, which leads to the observed tetrahedral structure around the water center, with a 50:50 disorder regarding the water as well as the pyrazole protons.

107 3 Results and Discussion

3.3.4 Poly(cobalt(II)acetylacetonato-bis(1,4-bis(3,5-dimethylpyrazol- 4-yl)butadiyne)) (38/39)

Having obtained the unprotected 1,4-bis(3,5-dimethyl-1H -pyrazol-4-yl)butadiyne (37), the next step was, to synthesize a ﬁrst coordination polymer thereof. This could be accomplished by mixing a solution of the ligand in acetone with a solution of cobalt(II)- acetylacetonate, likewise dissolved in acetone. The product immediately precipitated as an insoluble violet powder. The composition of the obtained compound was ﬁrst determined via elemental analysis. The results suggested, that ligand 37 was deprotonated by acetylacetonate, thus enabling it to bind one cobalt atom with each nitrogen donor function. Since one acetylacetonato ligand gets protonated during the reaction, only one such ligand remains at each cobalt center.

HN NH N N

Co(acac) 2 acetone - Hacac

O O Co N N N N Co O O

38 n

Scheme 3.35: Synthesis and proposed structure of poly(cobalt(II)acetylacetonato- bis(1,4-bis(3,5-dimethylpyrazol-4-yl)butadiyne)) (38).

These considerations led to the proposed structure of the obtained compound depicted in scheme 3.35. This suggestion however was thus far solely based on the elemental composition. Therefore, the residue of the reaction was analyzed via 1H NMR spectroscopy. The spectrum exposed the predicted acetylacetone as a tautomeric keto enol equilibrium with the signals of the prevalent enol form at 2.05 and 5.50 ppm. The keto form was indicated by singlets at 2.24 and 3.59 ppm. These ﬁndings supported the proposed structure presented above. However, a variety of diﬀerent structures with this composition

108 3.3 Coordination Polymers of 1,4-Bis(1H-pyrazol-4-yl)butadiynes are possible and while very similar coordination modes have been reported for several compounds in literature,[202] it is not possible to definitely confirm one of them without an X-ray structure determination. As was recently shown by Navarro and Zhu (see chapter 1.6.3), pyrazole based coordination polymers can also result in higher order three dimensional structures.[176,180–182] While a blue single crystal suitable for X-ray structure determination could be obtained by slow evaporation of a highly diluted solution of ligand 37 and cobalt(II)acetylacetonate in methanol, the structure which was revealed therein, did not match the composition of the aforementioned violet powder. Instead a one dimensional chain of cobalt(II)acetylacetonate alternating with ligand units and bonded in a κ1 fashion are observed (39). The deprotonation of the amine function by one of the acetylacetonato ligands did not occur, as can be seen in figure 3.15, in which one repetition unit of the 1D coordination polymer is depicted.

Figure 3.14: Preliminary molecular structure of two strands of 39. Thermal ellipsoids are drawn at the 50 % probability level. Hydrogen atoms and water molecules have been omitted for clarity.

The compound crystallized in the triclinic crystal system in the space-group P−1. Se- lected bond lengths and angles are listed in table 3.10. The packing motif of 39 is depicted in ﬁgure 3.14. The single strands of the polymer are therein layered orthogonally to each other. The pyrazole rings show parallel-displaced π − π stacking. The distance between the pyrazole rings amounts to 3.4293(76) Å. The linear strands result from trans coordination of the metal centers to the ligand molecules. The structure determination showed, that the cobalt centers in the polymer are sixfold coordinated in a only slightly distorted octahedron. The angle N1-Co1-O2 amounts to 90.22(4)◦ and the angle between the oxygen donors of the acetylacetonato ligands measures 90.48(15)◦. They are both close to

109 3 Results and Discussion

Figure 3.15: Preliminary molecular structure of one repetition unit of 39. Thermal ellipsoids are drawn at the 50 % probability level. Most hydrogen atoms and water molecules have been omitted for clarity. the ideal value of 90◦. Furthermore, the coordinative bonds have lengths of 2.150(4) Å (N1-Co1) and 2.042(4) Å (Co1-O1). The bond lengths of the carbon atoms of the butadiyne linker are close to the ideal values for such a system. The triple bonds amount to 1.190(6) Å, which is close to the literature value of 1.20 Å. The bonds between the sp2-sp carbon atoms (C4-C6) have lengths of 1.425(6) Å and the single bond between the two sp hybridized carbon atoms C7A and C7B amounts to 1.382(9) Å. Both values agree well with the literature values of 1.43 Å and 1.37 Å, respectively. This clearly shows that there are no conjugation eﬀects but instead two discrete triple bonds in this compound.[200]

Distances (Å) N1-N2 1.352(5) N1-C5 1.320(6) N2-C3 1.336(6) C4-C6 1.425(6) C3-C4 1.367(7) C4-C5 1.409(6) C6-C7 1.190(6) C7A-C7B 1.382(9) N1-Co1 2.150(4) Co1-O1 2.042(4)

Angles (deg) N1-N2-C3 113.0(4) N2-N1-C5 105.2(4) O1-Co1-O2 90.48(15) N1-Co1-O2 90.22(4)

Table 3.10: Selected interatomic distances (Å) and angles (deg) for compound 39.

110 3.3 Coordination Polymers of 1,4-Bis(1H-pyrazol-4-yl)butadiynes

3.3.5 Poly(cobalt(II)chlorido-bis(1,4-bis(3,5-dimethyl-1H-pyrazol-4- yl)butadiyne)) (40)

Since the reaction of ligand 37 with cobalt(II)acetylacetonate led most likely to deprotonation of the ligand by the involved acetylacetonato ligands of the metal salt, the metal fragment was changed to cobalt(II)chloride. Deprotonation of the amine function by chloride was not supposed to occur for hydrochloric acid is the stronger acid compared to the protonated ligand. Instead, a κ1 coordination motif was expected.

HN NH N N

CoCl2 acetone

HN NH Cl N N Co Cl 40 n

Scheme 3.36: Synthesis and proposed structure of poly(cobalt(II)chlorido-bis(1,4- bis(3,5-dimethyl-1H-pyrazol-4-yl)butadiyne)) (40).

Therefore, an equimolar solution of 1,4-bis(3,5-dimethyl-1H -pyrazol-4-yl)butadiyne (37) and cobalt(II)chloride in acetone was stirred at room temperature. In contrast to polymer 38, no reaction could be observed after 24 hours. While heating the reaction mixture to reﬂux for another 24 hours, the desired compound was obtained in good yields as a blue powder. As stated for compound 38, it is not possible to clarify unambiguously the structure of the obtained polymer without an X-ray structure determination, especially since the substance is completely insoluble in common solvents. Elemental analysis however strongly supports the structure, which is presented in scheme 3.36. As discussed above, the ligand was not deprotonated by the very weak base chloride. Thus, only a κ1 coordination of the ligand by a single cobalt dichloride center is possible. A structure similar as the one found in the X-ray analysis of 39 (see chapter 3.3.4) is therefore assumed. Nevertheless, higher dimensional coordination polymer structures than the proposed one dimensional chain cannot be ruled out entirely. In an attempt to obtain another cobalt(II)dihalide polymer, the synthesis was repeated

111 3 Results and Discussion with the corresponding bromide salt. In this case however, no reaction could be observed, even by continuous stirring under reﬂux in solvents like acetonitrile.

HN NH N N

CoBr2 acetone/acetonitrile

HN NH Br N N Co Br 41 n

Scheme 3.37: Attempted synthesis of poly(cobalt(II)bromido-bis(1,4-bis(3,5-dimethyl- 1H-pyrazol-4-yl)butadiyne)) (41).

A possible explanation for this behavior could be the increased sterical demand of the bromido substituents compared to the chlorido substituents. This could for example lead to an interference with the methyl substituents of the ligand.

Summary

So far, it was possible to obtain the unprotected 1,4-bis(3,5-dimethyl-1H -pyrazol-4-yl)butadiyne (37) ligand. This ligand tends to form polymers by itself, due to its pyrazole moieties, which can act at the same time as hydrogen bond donors and acceptors. This was also confirmed by an X-ray structure determination. Based on this ligand 37, the structure of the 1D coordination polymer poly(cobalt(II)- acetylacetonato-bis(1,4-bis(3,5-dimethyl-1H -pyrazol-4-yl)butadiyne)) (39) could be clar- ified, which is the first coordination polymer, in which 37 is incorporated in its neutral form instead of its anionic form. However, this material could only be obtained as a crystal. The direct reaction of 37 with cobalt(II)acetylacetonate led to the formation of a polymer containing 37 in its deprotonated state 38. Therefore, the synthesis of coordination polymers of copper(II)dihalides was attempted, since the halides, as weaker bases compared to acetylacetonate, should not be able to deprotonate 37. This assumption was confirmed. The corresponding copper(II)chloride based polymer of 37, poly(cobalt(II)chlorido-bis(1,4-bis(3,5-dimethyl-1H -pyrazol-4-yl)bu-

112 3.3 Coordination Polymers of 1,4-Bis(1H-pyrazol-4-yl)butadiynes tadiyne)) (40), could be obtained. However, the synthesis of the corresponding copper(II)- bromide coordination polymer was not successful so far.

113 3 Results and Discussion

3.3.6 4-Ethynyl-1-tritylpyrazole (42)

In another approach, the synthesis of 4-ethynyl-1-tritylpyrazole (42) was attempted. Therefore, the previously discussed compound 27 (see chapter 3.2.12) was deprotected under basic conditions, to enable it to undergo Glaser type coupling reactions as shown in chapter 3.3.1). Reaction with potassium carbonate in a mixture of tetrahydrofuran and methanol led to the removal of the trimethylsilyl protecting group, while leaving the trityl group in place, which is useful to avoid the immediate formation of coordination polymers in the subsequent Eglinton coupling step. The desired compound 42 could be obtained in yields of 73 %.

N K2CO3 N Si N THF/MeOH N

27 42

Scheme 3.38: Synthesis of 4-ethynyl-1-tritylpyrazole (42).

The successful deprotection could be conﬁrmed via 1H NMR spectroscopy. While a new signal at 3.01 ppm was found and assigned to the terminal proton of the alkyne moiety, no more resonances of the TMS protecting group could be observed. The remaining signals of the trityl group (7.13 and 7.19 ppm) as well as the the signals of the pyrazole ring protons at 7.56 and 7.77 ppm, respectively, remained almost unchanged. The resonances of the alkyne moiety in the 13C NMR spectrum are shifted upﬁeld by 20 ppm to 75.4 and 78.3 ppm.

3.3.7 1,4-Bis(1-tritylpyrazol-4-yl)butadiyne (43)

As already shown for the dimethyl substituted compound 36, the next step consisted of an Eglinton homo coupling step. In this case, the product 43 showed a signiﬁcantly higher solubility in chlorinated solvents than its substituted counterpart 36 and was thus extracted with dichloromethane. Compared to 37 could be obtained as a white powder in yields of 66 %. The 1H NMR spectrum of compound 43 showed signals of the trityl protecting group at 7.14 and 7.33 ppm as multiplets, while the protons of the pyrazole rings resonate at chemical shifts of 7.58 and 7.78 ppm. In the 13C NMR spectrum, the signals of the butadiyne carbon atoms appear at 72.8 and 74.8 ppm, respectively. The trityl protecting group are assigned to the signals at 79.3,

114 3.3 Coordination Polymers of 1,4-Bis(1H-pyrazol-4-yl)butadiynes

2 N N

Cu(OAc)2 MeCN/pyridine

N N N N 43

Scheme 3.39: Synthesis of 1,4-bis(1-tritylpyrazol-4-yl)butadiyne (43).

127.9, 128.0, 130.1 and 136.6 ppm. Furthermore, the carbon atoms of the pyrazole rings are detected at chemical shifts of 100.8, 142.4 and 142.9 ppm. These ﬁndings agree well with the signals found for the dimethyl substituted compound 36.

3.3.8 Attempted Synthesis of 1,4-Bis(1H-pyrazol-4-yl)butadiyne (44)

While the precursors of 44 could be obtained in generally the same way as the precursors of the dimethyl substituted 37, it was not possible to remove the trityl protecting group from the nitrogen donor of 43 with triﬂuoroacetic acid. This was independent of the applied temperature or concentration of this reagent. Similar procedures involving hydrochloric acid or acetic acid did not lead to the desired product, either. However, reacting compound 43 with a Lewis acid, in this case boron tribromide, led to promising results, as depicted in scheme 3.40. Yet, no viable method for the puriﬁcation of 44 could be found during the course of this thesis. The 1H NMR spectrum of a bright green crude sample, taken during the reaction as reaction control, of compound 44 revealed only one signal, apart from solvent signals: a singlet at 7.31 ppm, which refers to the four protons of the pyrazole rings. This would agree nicely with the expected signal for the desired compound. More information could be gained from the 13C NMR spectrum of this sample. Only one

115 3 Results and Discussion

N N N N 43

BBr3 CH2Cl2

HN NH N N 44 ?

Scheme 3.40: Attempted synthesis of 1,4-bis(1H-pyrazol-4-yl)butadiyne (44). signal typical for an sp hybridized carbon atom could be observed at a chemical shift of 2 82.8 ppm or possibly the sp C4 pyrazole carbon atom. At 127.7 and 130.6 ppm appear two singlets with relatively high intensities, indicating carbon atoms, which carry protons. Therefore, they were assigned to the carbon atoms C3 and C5 of the pyrazole rings. The remaining two singlets at 127.8 and 145.6 ppm could be caused by the remaining atoms of the butadiyne linker. In this case, the discrete triple bonds of the linker group would be deallocated in favor of an cumulene like structure. A set of signals in this area would be typical for [5]cumelenes (e.g. tetraferrocenyl[5]cumulene 119.8, 119.9 and 140.8 ppm).[203,204] Yet, after quenching of the reaction mixture, this product could not be isolated.

HN NH ? N N C C C C N N -H2 N N 44

Scheme 3.41: Possible oxidation product of 1,4-bis(1H-pyrazol-4-yl)butadiyne (44).

This hypothesis is supported by the IR spectrum of the crude product. Therein, the initial C≡C band of the educt is accompanied by a second band at 1958 cm−1 in the spectrum of 44 (e.g. tetraferrocenyl[5]cumulene 1973 cm−1).[203–205] In order to react to a cumelene, molecular hydrogen must have been released and 44 must have been oxidized during this reaction as depicted in scheme 3.41. The bright green color

116 3.3 Coordination Polymers of 1,4-Bis(1H-pyrazol-4-yl)butadiynes of the crude sample, that was taken and analyzed during the reaction, might indicate the involvement of radical species during the reaction. However, while these are surely interesting ﬁndings, there is more investigation needed in future works to further elucidate this topic.

117 3 Results and Discussion

3.4 Ferrocene Based Models for Rieske Dioxygenases

Apart from the above presented model systems for DMSO reductases, a model system for Rieske dioxygenases was to be synthesized. The most important aspect of these compounds are, besides their coordination motif, the electrochemical properties. As stated in chapter 1.3, ferrocene is a compound, that is widely used in this context due to its distinct electrochemical properties.[64,66,71,77,206]

N N O O N N Fe e-

Figure 3.16: Possible electron transfer in a ferrocene based bis(pyrazolyl)acetate model system.

Recent attempts to use ferrocene in combination with scorpionate ligands and more speciﬁ- cally ferrocene substituted bis(pyrazolyl)acetic acids were undertaken by S. Tampier and S. Bleifuss.[71] In order to resemble the active site of a Rieske dioxygenase, ferrocene was supposed to serve as an electron reservoir, which would transfer electrons towards an iron center, which is κ3 N,N,O coordinated by the ligand. One potential variant of such a system is depicted in scheme 3.16.

R R R O R

N N N N N N N N Fe Fe Fe Fe R R R R R = H bfcpzm R = H bfcpzk R = CH3 bfcdmpzm R = CH3 bfcdmpzk

Figure 3.17: Selected ferrocenyl pyrazole compounds by Tampier et al.[71]

The reaction pathway was based on the work of Mochida et al., who recently reported on the synthesis of 4-ferrocenyl-1H -pyrazoles. These were obtained via Negishi type coupling reactions of 4-iodopyrazoles with ferrocene.[77] Starting from there, the corresponding 4-ferrocenylpyrazoles were reacted to bis(pyrazolyl)methanes, -ketones and -acetic acids via phase transfer reactions as already discussed in chapter 1.1.2.[71]

118 3.4 Ferrocene Based Models for Rieske Dioxygenases

While the bis(pyrazolyl)methanes and -ketones could be obtained in a pure form, Tam- pier and Bleifuss did not succeed to isolate the desired tripodal bis(4-ferrocenyl-3,5- dimethylpyrazol-1-yl)acetic acid. However, the electrochemical potentials of the obtained compounds was promising.[71] In this work, similar ligands for Rieske model systems are reported. These ligands however do not contain ferrocene, which is directly bonded to the pyrazole rings. Instead the ferrocenyl moieties were attached via triazole units (by Click chemistry) and via acetylene linkers (by Sonogshira coupling reactions) as shown in scheme 3.42.

CuSO4 N N 3 Sodium ascorbate N N Fe + Fe N N N N

[PdCl2(PPh3)2] N CuI N I + Fe N DMF, NEt3 N Fe

Scheme 3.42: Exemplary syntheses for ligands suitable for Rieske model systems.

In order to obtain these ligands, the corresponding ethynyl substituted ligand precursor bis(4-ethynyl-3,5-dimethylpyrazol-1-yl)methane (15) was reacted with ferrocenyl azides in copper(I)-catalyzed alkyne-azide cycloadditions (scheme 3.42 top). The iodinated ligand precursors for the Sonogashira coupling reactions (scheme 3.42 bottom) on the other hand were prepared as shown in the following chapter.

119 3 Results and Discussion

3.4.1 Bis(4-iodo-3,5-dimethylpyrazol-1-yl)methane (45)

For the synthesis of acetylene linked Rieske dioxygenase models, it was necessary to first synthesize iodo substituted bispyrazolyl precursors. Such compounds could later be employed in Sonogashira reactions to obtain the desired model systems. The first precursor of this kind was the N,N coordinating bis(4-iodo-3,5-dimethylpyrazol- 1-yl)methane (45). This compound was first synthesized by Potapov et al. from 1,1’- methylenebis(pyrazole) in 2006.[207] From there, the group used iodine and iodic acid in a mixture of acetic acid and sulphuric acid for the iodination.[207] However, instead of following this procedure, the synthesis presented herein started from the above mentioned 4-iodo-3,5-dimethylpyrazole (23, see chapter 3.2.9). Two equivalents of 23 were connected to the corresponding bis(pyrazol-1-yl)methane 45 by a phase transfer reaction in dichloromethane, which served as reactant as well as a solvent. The reaction was catalyzed by benzyltriethylammoniumchloride (BTEAC) as a phase transfer catalyst. This synthetic route is based on the report of Juliá et al. regarding bispyra- zolylmethane.[43]

KOH, K2CO3, NH BTEAC N N 2 I I I N CH2Cl2 N N

45 23

Scheme 3.43: Synthesis of bis(4-iodo-3,5-dimethylpyrazol-1-yl)methane (45).

The spectroscopic data agreed with those reported by Potapov et al.[207] The 1H NMR spectrum shows the methyl substituents of the pyrazole rings at chemical shifts of 2.19 and 2.47 ppm respectively. The protons of the introduced methylene bridge are detected at 6.14 ppm. Furthermore, the 13C NMR spectrum of 45 shows the resonances of the four methyl groups at 12.2 and 14.0 ppm. The iodinated carbon atoms are strongly shifted upﬁeld to 62.0 ppm. The carbon atom of the methylene bridge is detected at 65.1 ppm and the signals at 142.1 and 150.4 ppm can be assigned to the remaining carbon atoms of the pyrazole rings.

3.4.2 Bis(4-iodopyrazol-1-yl)methane (46)

While the procedure of Juliá et al.[43] led to good results for the synthesis of bis(4- iodo-3,5-dimethylpyrazol-1-yl)methane (45) as was discussed above, the same protocol was not applicable for the synthesis of bis(4-iodopyrazol-1-yl)methane (46) using from

120 3.4 Ferrocene Based Models for Rieske Dioxygenases

4-iodopyrazole (22), instead. Surprisingly not the anticipated methylene bridged product, but the corresponding carboxylic acid 47 was obtained as it is depicted in scheme 3.44. The actually desired product could only be obtained in yields of 3 % as a side product. The source of the carboxyl group is most likely the potassium carbonate, which is used as base during the phase transfer reaction.

N N I I N N

KOH, K2CO3, 46 NH BTEAC 2 I N CH2Cl2 CO2H 22 N N I I N N 47

Scheme 3.44: Attempted synthesis of bis(4-iodopyrazol-1-yl)methane (46).

This changed reactivity must be caused by the activation of the pyrazoles by the iodine substituent in position 4 of the pyrazole ring. Thus, the synthesis of 46 was carried out in two steps, as proposed by Potapov et al. (see chapter 3.4.1).[207] Yet, the iodination conditions were changed to the milder combination of iodine and cer(IV)ammoniumnitrate.

[NH4]2[Ce(NO3)6] N N I N N 2 I I N N N N 46

Scheme 3.45: Synthesis of bis(4-iodopyrazol-1-yl)methane (46).

By this procedure, the desired bis(4-iodopyrazol-1-yl)methane (46) could be isolated in almost quantitative yields. The spectroscopic data obtained from this compound agree with the ﬁnding of Potapov et al.[207] The 1H NMR spectrum shows one signal for the protons of the methylene bridge at 6.24 ppm. The protons in positions 5 and 3 of the pyrazole rings are detected at chemical shifts of 7.56, respectively 7.69 ppm. The signal at 58.6 ppm of the 13C NMR spectrum could be assigned to iodine substituted carbon atoms of the pyrazole rings. The methylene bridge is detected at 65.3 ppm. The remaining carbon atoms of the pyrazole moieties lead to signals at 134.0 and 146.0 ppm.

121 3 Results and Discussion

3.4.3 Bis(4-iodopyrazol-1-yl)acetic acid (47) and Bis(4-iodo-3,5-dimethylpyrazol-1-yl)acetic acid (48)

Having obtained the desired N,N coordinating precursors 45 and 46, the corresponding N,N,O coordinating ligands were to be synthesized. The synthesis was based on the one pot procedure reported by Burzlaff et al.[11] The two educts 4-iodopyrazole 22 and 4- iodo-3,5-dimethylpyrazole 23 were deprotonated with a mixture of potassium carbonate and potassium hydroxide under phase transfer conditions in tetrahydrofuran. As phase transfer catalyst, BTEAC was used. The reaction with dibromoacetic acid leads to the formation of the corresponding carboxylates bis(4-iodo-3,5-dimethylpyrazol-1-yl)acetic acid (48) and bis(4-iodopyrazol-1-yl)acetic acid (47). The desired compounds could be extracted from an aqueous solution after acidic workup.

CO2H

KOH, K2CO3, NH BTEAC, Br CHCO H N N 2 I 2 2 I I N THF N N 47 22

CO2H

KOH, K2CO3, NH BTEAC, Br CHCO H N N 2 I 2 2 I I N THF N N 48 23

Scheme 3.46: Synthesis of bis(4-iodopyrazol-1-yl)acetic acid (47) and bis(4-iodo-3,5- dimethylpyrazol-1-yl)acetic acid (48).

The spectrum of compound 48 contains two singlets for the methyl substituents of the pyrazole rings at 2.24 and 2.26 ppm. The proton of the methine bridge can be found at 7.00 ppm. The 1H NMR spectrum of compound 47 displays the signals of the methine bridge at a chemical shift of 7.22 ppm. The pyrazole protons in position 5 and 3 of the pyrazole rings are detected at 7.60 and 7.93 ppm, respectively. Furthermore, the products were analyzed via 13C NMR spectroscopy. The spectrum of compound 47 shows the iodo substituted carbon atom in position 4 of the pyrazole ring at 59.4 ppm. The bridging carbon atom is detected at 75.3 ppm. The remaining carbon atoms of the pyrazole rings are found at 136.6 and 147.19 ppm. The carbon atom of the carboxyl group has a chemical shift of 165.6 ppm. Apart from the two additional signals of the methyl substituents at 12.3 and 14.1 ppm, the 13C NMR spectrum of compound 48 agrees with these ﬁndings. At 67.1 ppm, the

122 3.4 Ferrocene Based Models for Rieske Dioxygenases iodo substituted carbon atom is found, followed by the signal of the methine bridge at 71.9 ppm. The remaining pyrazole carbon atoms are detected at 143.1 and 151.3 ppm and the carboxyl group at 164.5 ppm, clearly indicating the successful synthesis of the desired compounds.

3.4.4 Methyl Bis(4-iodopyrazol-1-yl)acetate (49) and Methyl Bis(3,5-dimethyl-4-iodopyrazol-1-yl)acetate (50)

The obtained N,N,O coordinating iodinated derivatives 47 and 48 were to be esteriﬁed in the next step, since the free carboxylic acids prevented their application in Sonogashira reactions. For the esteriﬁcation, the corresponding educts were dissolved in methanol. Some drops of sulfuric acid were added, to provide the required catalytical concentration of protons for the reaction, as it is depicted in scheme 3.47. After three days, both products could be obtained in yields of 40 - 50 %.

O O CO2H

N N MeOH, H SO N N I I 2 4 I I N N N N 47 49

O O CO2H

N N MeOH, H SO N N I I 2 4 I I N N N N 48 50

Scheme 3.47: Synthesis of methyl bis(4-iodopyrazol-1-yl)acetate (49)) and methyl bis(3,5-dimethyl-4-iodopyrazol-1-yl)acetate (50).

The 1H NMR spectra of both products clearly indicate the success of the esteriﬁcation processes. The spectrum of 50 contains two singlets of the methyl substituents of the pyrazole rings at 2.21 and 2.23 ppm. The signal of the proton of the methine bridge remains unchanged as well at 7.01 ppm. However, the singlet at 3.89 ppm can be assigned to the methyl ester. The corresponding 13C NMR spectrum exhibits the signals of the two methyl substituents of the pyrazole rings at 12.3 and 14.1 ppm. The relevant signal of the methyl ester is detected at 53.7 ppm. The singlet of the methine bridge carbon atom is found at 74.0 ppm. The four remaining signals can be assigned to the pyrazole carbon atoms at 68.0, 142.7 and 150.7 ppm and to the carbon atom of the carboxylate group at 164.5 ppm.

123 3 Results and Discussion

A similar situation can be found in the 1H NMR spectrum of compound 49. The methyl ester is therein detected at 3.89 ppm. The remaining protons are found at 7.00 ppm for the methine group and 7.60 and 7.80 ppm for the remaining protons of the pyrazole rings. In the 13C NMR spectrum of compound 49, the methyl ester group is found at 54.1 ppm. The chemical shift of the methine carbon atom is 74.3 ppm and the carbon atoms of the pyrazole rings are detected at 59.1, 134.5 and 146.2 ppm. The signal at 163.9 ppm can be assigned to the carboxylate.

124 3.4 Ferrocene Based Models for Rieske Dioxygenases

3.4.5 Bis(4-ethynylferrocenylpyrazol-1-yl)methane (befcpzm) (51)

Using the so far discussed iodinated ligand precursors, it was now possible to synthesize first ligands suitable as models for Rieske dioxygenases. In a first attempt, a palladium catalyzed Sonogashira reaction was carried out to react ethynylferrocene with bis(4- iodopyrazol-1-yl)methane 46 (see chapter 3.4.3). Bis(triphenylphosphine)palladium dichloride was hereby used as catalyst and copper(I) iodide as co-catalyst. The resulting crude product bis(4-ethynylferrocenylpyrazol-1-yl)methane (befcpzm) (51) was purified via column chromatography (see scheme 3.48).

N N I I + 2 Fe N N 46

[PdCl2(PPh3)2] CuI, DMF, NEt3 60 °C

N N N N Fe 51 Fe

Scheme 3.48: Synthesis of befcpzm (51).

The 1H NMR spectrum of compound 51 shows the signals of the β protons of the cyclopentadienyl rings at 4.22 ppm. The α protons were found at 4.45 ppm and the protons of the unsubstituted rings appeared at 4.23 ppm. The methylene bridge was detected at 6.23 ppm and the remaining protons of the pyrazole rings are observed at 7.66 and 7.78 ppm. Two signals in the 13C NMR spectrum could not be assigned unambiguously. They appear at 65.1 and 65.5 ppm, respectively. One of them is caused by the bridging carbon atom, while the other signals belongs to the quaternary carbon atoms of the cyclopentadienyl rings. The remaining signals of the ferrocenyl moieties are detected at 68.7, 69.9 and 71.2 ppm. The signals at 75.6 and 89.4 ppm could be assigned to the carbon atoms of the acetylene linkers. Their anchor point in position 4 of the pyrazole rings is found at a chemical shift of 105.9 ppm, while the remaining pyrazole carbon atoms appear at 131.8 and 143.2 ppm, respectively. The cyclic voltammogram of befcpzm (51) shows one reversible redox process with an

125 3 Results and Discussion

-5 0.1 V/s

1.6x10

0.2 V/s

-5

0.3 V/s 1.2x10

0.4 V/s

-6

8.0x10 0.5 V/s

-6

4.0x10

0.0 I (A) I

-6

-4.0x10

-6

-8.0x10

-5

-1.2x10

-5

-1.6x10

-0.4 -0.2 0.0 0.2

U (V) vs Fc/Fc

Figure 3.18: Cyclic voltammogram of befcpzm (51) in acetonitrile under nitrogen atmo- ◦ −4 sphere at 25 C. Conditions: 51: 5 × 10 mol/L, [NBu4][PF6]: 0.1 mol/L, scan rates: 0.1 V/s, 0.2 V/s, 0.3 V/s, 0.4 V/s, 0.5 V/s. oxidation potential of +170 mV and a reduction potential of +83 mV versus Fc/Fc+. With these values, the half wave potential calculates to +127 mV. However, as reported by S. Tampier, the lacking methyl substitution and thus missing +I eﬀect tend to lead to higher reduction potentials.[71] Under the applied conditions, there was no electronic communication between the ferrocenyl moieties indicated so far. Interestingly, it was not possible to synthesize similar compounds with 3,5-dimethyl substituted pyrazole moieties. This was surprising, since sterical hindrance as the most striking reason for this behavior appears unlikely considering the fact, that it was possible to directly bind ferrocene rings to 3,5-dimethylpyrazoles by a Negishi coupling reaction utilizing the same catalyst as reported by S. Tampier.[71] A single crystal suitable for X-ray structure determination could be obtained by slowly evaporating a solution of 51 in ethyl acetate and n-hexane. The molecular structure is depicted in ﬁgure 3.19. Selected angles and bond lengths are listed in table 3.11. The structure has a C2 symmetry axis. The bond lengths of the acetylene linker are close to the ideal values for a unconjugated system with discrete triple and single bonds. The lengths of the triple bond between

126 3.4 Ferrocene Based Models for Rieske Dioxygenases

Figure 3.19: Crystal structure of befcpzm (51). Thermal ellipsoids are drawn at the 50 % probability level. Hydrogen atoms have been omitted for clarity.

C5 and C6 amounts to 1.205(5) Å, which is close to the literature value of 1.20 Å.[200] The bond lengths between the sp2-sp carbon atoms (C3-C5 and C6-C7) are measured to be 1.426(6) Å and 1.421(5) Å, respectively. These values agree with the literature value of 1.43 Å for a sp2-sp bond, too.[200] Furthermore, the linker is bent slightly. The angles between C3-C5-C6 and C5-C6-C7 deviate from the ideal 180◦ by 5.9◦ and 2.0◦, respectively. The torsion angle between the pyrazole ring and the cyclopentadienyl ring 6 (C4-C3-C7- C8) is 39.9(1)◦. Therefore, the tilt between the ferrocenyl moieties and the pyrazole rings is larger than for systems, in which ferrocene is bonded directly to pyrazole in position 4. For bis(4-ferrocenylpyrazol-1-yl)methane, this angle is 19.81(37)◦ and 6.16(38)◦, respectively [195] (the structure is not C2 symmetric).

Distances (Å) C1-N2 1.447(4) N1-N2 1.354(4) N1-C4 1.326(5) N2-C2 1.351(4) C2-C3 1.384(6) C3-C4 1.416(5) C3-C5 1.426(6) C5-C6 1.205(5) C6-C7 1.421(5)

Angles (deg) N2-C1-N2 110.7(4) C1-N2-N1 118.9(2) C2-C3-C4 104.3(3) C2-N2-N1 112.7(3) C3-C5-C6 174.1(4) C5-C6-C7 178.0(4) C4-C3-C7-C8 39.9(1)

Table 3.11: Selected interatomic distances (Å) and angles (deg) for compound 56.

127 3 Results and Discussion

3.4.6 Methyl bis(4-ethynylferrocenylpyrazol-1-yl)acetate (mbefcpzac) (52)

Yet to mimic a Rieske dioxygenase, a N,N,O binding motif instead of the so far presented presented N,N coordinating ligand would be preferable since it would resemble the 2-His- 1-carboxylate triade more closely.[89,92] However, in previous works, it was not possible to synthesize ferrocenyl substituted bis(pyrazol-1-yl)acetic acids in a useful scale.[71] By performing a Sonogashira reaction with ethynylferrocene and methyl bis(4-ethynylpyrazol-1-yl)acetate (49, see chapter 3.4.6), it was possible to take an important step in this direction. The esteriﬁcation of the precursor compound was necessary since Sono- gashira reactions with carboxylic acids are usually not successful. The reaction was carried out in accordance to the synthesis of compound 51 (see chapter 3.4.5) to obtain methyl bis(4-ethynylferrocenylpyrazol-1-yl)acetate (mbefcpzac) (52).

O O

N N I I + 2 Fe N N 49

[PdCl2(PPh3)2] CuI, DMF, NEt3 60 °C

O O

N N N N Fe 52 Fe

Scheme 3.49: Synthesis of mbefcpzac (52).

In the 1H NMR spectrum of mbefcpzac (52), the methyl ester group is detected at 3.91 ppm. The signal of the unsubstituted cyclopentadienyl rings appears at 4.24 ppm and the β protons of the substituted rings appear as a shoulder at 4.23 ppm. The corresponding α protons are found at 4.46 ppm. The proton of the methine bridge has a chemical shift of 6.99 ppm. The remaining pyrazole protons are detected at 7.70 and 7.88 ppm, respectively. The 13C NMR conﬁrms the product formation as well. The methyl ester is detected

128 3.4 Ferrocene Based Models for Rieske Dioxygenases at 54.0 ppm. The signal at 74.6 ppm is assigned to the methine bridge. The ferrocene moieties are detected at 68.8, 69.9, 71.3 and 75.4 ppm. The presence of the triple bonds is conﬁrmed by signals at 82.8 and 106.2 ppm. The pyrazole rings are assigned to the signals at 132.3, 143.4 and 146.8 ppm. The carboxylate carbon atom is found at 164.00 ppm.

-6

4.0x10

0.1 V/s

0.2 V/s

-6

3.0x10

0.3 V/s

0.4 V/s

-6

2.0x10

0.5 V/s

-6

1.0x10

0.0 I (A) I

-6

-1.0x10

-6

-2.0x10

-6

-3.0x10

-6

-4.0x10

-0.4 -0.2 0.0 0.2

U (V) vs Fc/Fc

Figure 3.20: Cyclic voltammogram of mbefcpzac 52 in acetonitrile under nitrogen atmo- ◦ −4 sphere at 25 C. Conditions: 52: 5 × 10 mol/L, [NBu4][PF6]: 0.1 mol/L, scan rates: 0.1 V/s, 0.2 V/s, 0.3 V/s, 0.4 V/s, 0.5 V/s. Rippled noise due to low solubility of 52.

The cyclic voltammogram of mbefcpzac (52) once again shows one reversible redox process with an oxidation potential of +176 mV and a reduction potential of +83 mV. The half wave potential therefore calculates to +130 mV versus Fc/Fc+. In comparison to befcpzm (51), which features the same ferrocenyl moieties, yet does not have the ester group, the difference of the half wave potential only amounts to 3 mV (see chapter 3.4.5). This shows that there is only a minor influence of the ester group on the overall potential. As shown previously, electron withdrawing groups at the bridging carbon atom, especially keto functions, can have a way more significant influence.[71] As stated for befcpzm (51, see chapter 3.4.5), the missing electron donating methyl substituents at the pyrazole rings have an undesired influence on the measured potential by leaving the pyrazole moieties more electron deficient than comparable 3,5-dimethyl

129 3 Results and Discussion substituted compounds. However, as already discussed for compound 51 the attempted synthesis of the respective substituted species was not successful so far.

3.4.7 Bis((4-ethynyl-1-ferrocenylphen-4-yl)-3,5-dimethylpyrazol-1- yl)methane (bepfcdmpzm) (53)

In order to decrease the half wave potential further towards values within the range of Rieske clusters, the ferrocenyl substituent was modiﬁed by a moiety with a larger aromatic linker. This should on the one hand lower the redox potential of the resulting products and on the other hand enable the synthesis with 3,5-dimethyl substituted pyrazole rings by placing the sterically demanding ferrocenyl unit further away from the active site of the coupling reaction. One ferrocenyl precursor that, in comparison to ethynylferrocene, has been shown to inﬂuence the potential in such a way, is 1-ferrocenyl- 4-ethynylbenzene, as was previously published for pyrazabole compounds by Mobin and coworkers.[208,209] This precursor was synthesized by a diazotization reaction starting from 4-ethynylaniline and subsequent reaction with ferrocene.[210]

N N I I + 2 Fe N N 45

[PdCl2(PPh3)2] CuI, DMF, NEt3 60 °C

N N N N Fe 53 Fe

Scheme 3.50: Synthesis of befcpdmpzm (53).

The actual product synthesis was again carried out via a palladium catalyzed Sono- gashira reaction in dimethylformamide, yet this time with the 3,5-dimethyl substituted bis(4-iodo-3,5-dimethylpyrazol-1-yl)methane (45) as coupling partner. If only two equivalents of 1-ferrocenyl-4-ethynylbenzene were used in the reaction, the prevalent product was the mono substituted species ((4-ethynyl-1-ferrocenylphen-4-yl)-3,5-dimethylpyrazol- 1-yl)-(4-iodopyrazol-1-yl)methane. Yet, raising the ratio to four equivalents led to the for-

130 3.4 Ferrocene Based Models for Rieske Dioxygenases mation of the desired product bis((4-ethynyl-1-ferrocenylphen-4-yl)-3,5-dimethylpyrazol- 1-yl)methane (bepfcdmpzm) (53). Puriﬁcation of the crude product via column chromatography showed that larger quantities of the Glaser product of the ferrocenyl precursor was formed, although the reaction was carried out under careful exclusion of oxygen, which is usually needed to reoxidize the active copper species during Glaser coupling reactions.

-5

1.0x10 0.1 V/s

0.2 V/s

-6

8.0x10

0.3 V/s

-6

6.0x10 0.4 V/s

0.5 V/s

-6

4.0x10

-6

2.0x10

0.0 I (A) I

-6

-2.0x10

-6

-4.0x10

-6

-6.0x10

-6

-8.0x10

-0.4 -0.2 0.0 0.2

U (V) vs Fc/Fc

Figure 3.21: Cyclic voltammogram of befcpdmpzm (53) in acetonitrile under nitrogen ◦ −4 atmosphere at 25 C. Conditions: 53: 5 × 10 mol/L, [NBu4][PF6]: 0.1 mol/L, scan rates: 0.1 V/s, 0.2 V/s, 0.3 V/s, 0.4 V/s, 0.5 V/s.

The successful product formation could be confirmed by NMR spectroscopy as well as by mass spectrometry. In the 1H NMR spectrum, the methyl groups of the pyrazole rings are detected at 2.31 and 2.57 ppm, respectively. The proton signals of the cyclopentadienyl rings are shifted to 4.35 ppm for the β protons and 4.67 ppm for the α protons. The signal of the unsubstituted cyclopentadienyl rings is found at 4.05 ppm. With a chemical shift of 6.09 ppm, the methylene bridge can be observed. The signals of the phenylene rings appear as two doublets at 7.39 and 7.44 ppm with coupling constants of 8.29 and 8.48 Hz, respectively. These differ from the educt spectrum, in which these protons appear as one singlet at 7.42 ppm, thus confirming the successful synthesis. The 13C NMR spectrum shows the methyl groups at 10.8 and 12.6 ppm. The carbon atom

131 3 Results and Discussion of the methylene bridge can be found at 61.0 ppm. The signals at 66.5, 69.3, 69.7 and 80.2 ppm derive from the cyclopentadienyl rings. The acetylene bridges are detected at 84.3 and 93.5 ppm and the phenylene rings at 120.8, 125.8, 131.3 and 139.4 ppm. Finally, the carbon atoms of the pyrazole rings are assigned to the signals at 103.7, 143.2 and 150.6 ppm. The cyclic voltammogram of befcpdmpzm (53) shows one reversible redox process as for the previous compounds, as depicted in figure 3.21. The oxidation potential is measured to be +47 mV and the corresponding reduction potential to be −30 mV. Based on these values the half wave potential can be calculated to +9 mV. The enlarged aromatic system of the ferrocenyl moieties in combination with the +I-effect of the methyl substituents of the pyrazole rings led to a overall change of the half wave potential of −117 mV. This raises hope towards an adjustable system, where the potential of the ferrocenyl moieties can be fine tuned to negative values.

132 3.4 Ferrocene Based Models for Rieske Dioxygenases

3.4.8 Methyl bis((4-ethynyl-1-ferrocenylphen-4-yl)pyrazol-1- yl)acetate (mbepfcpzac) (54)

The same precursor was now to be incorporated into a N,N,O coordinating ligand as well. Therefore, once again a Sonogashira reaction was carried out. As for the synthesis of mbefcpzac (52), methyl bis(4-ethynylpyrazol-1-yl)acetate (49) was used, to obtain the desired N,N,O scorpionate ligand methyl bis((4-ethynyl-(1-ferrocenylphen-4-yl)pyrazol- 1-yl)acetate (mbepfcpzac) (54). An excess of 1-ferrocenyl-4-ethynylbenzene was again necessary to avoid the formation of the mono substituted product.

O O

N N I I + 2 Fe N N 49

[PdCl2(PPh3)2] CuI, DMF, NEt3 60 °C

O O

N N N N Fe 54 Fe

Scheme 3.51: Synthesis of mbepfcpzac (54).

The 1H NMR of mbepfcpzac (54) shows a singlet of the ester methyl group at 3.93 ppm. The cyclopentadienyl rings show basically the same chemical shifts as found for compound 53 with 4.05 ppm for the protons of the unsubstituted rings, 4.33 ppm for the β protons of the substituted rings and 4.66 ppm for the corresponding α protons. The hydrogen atom of the methine bridge is detected at 7.02 ppm. The two doublets at 7.40 and 7.44 ppm with coupling constants of 8.10 Hz and 8.48 Hz derive from the protons of the phenylene rings. Further downﬁeld, the protons of the pyrazole rings are assigned to the signals at 7.75 and 7.95 ppm. The 13C NMR spectrum of 54 shows the signal of the methyl ester at 30.0 ppm. The methine bridge is detected at 54.1 ppm. The ferrocene moieties are assigned to the signals at 66.5, 68.5, 69.3 and 69.7 ppm. The acetylene linkers were observed at 82.9 and

133 3 Results and Discussion

105.9 ppm and the phenylene moieties were observed at chemical shifts of 125.8, 131.4, 132.6 and 135.7 ppm. The remaining signals at 120.1, 139.9, 143.4 and 156.7 ppm were assigned to the pyrazole carbon atoms and the carboxylate, respectively.

-5

0.1 V/s 1.0x10

0.2 V/s

-6

8.0x10

0.3 V/s

-6 0.4 V/s

6.0x10

0.5 V/s

-6

4.0x10

-6

2.0x10

0.0 I (A) I

-6

-2.0x10

-6

-4.0x10

-6

-6.0x10

-6

-8.0x10

-0.4 -0.2 0.0 0.2

U (V) vs Fc/Fc

Figure 3.22: Cyclic voltammogram of mbepfcpzac (54) in acetonitrile under nitrogen ◦ −4 atmosphere at 25 C. Conditions: 54: 5 × 10 mol/L, [NBu4][PF6]: 0.1 mol/L, scan rates: 0.1 V/s, 0.2 V/s, 0.3 V/s, 0.4 V/s, 0.5 V/s.

The cyclic voltammogram of mbepfcpzac (54) shows one reversible redox potential with an oxidation potential of +68 mV and a reduction potential of −15 mV. With these values the half wave pontential calculates to +27 mV versus Fc/Fc+. Considering, that the influence of the additional methyl carboxylate group is only a minor one, as was shown for compounds 51 and 52, most of the potential difference to 53 derives from the absence of the methyl substituents at the pyrazole rings. However, the difference only calculates to 17 mV in this case, showing that for this system the methyl groups are only of minor importance for the optimization of the half wave potential.

134 3.4 Ferrocene Based Models for Rieske Dioxygenases

3.4.9 Bis(3,5-dimethyl-4-(1-ferrocenyl-1,2,3-triazol-4-yl)pyrazol-1- yl)methane (bdmfctpzm) (55)

Another approach to access ferrocenyl based chelate ligands relied on Click chemistry reactions instead of Sonogashira coupling reactions. Having obtained bis(4-ethynyl-3,5- dimethylpyrazol-1-yl)methane (bedmpzm) (15) as shown in chapter 3.2.2, it was possible to synthesize a first model complex for Rieske dioxygenases containing a triazole linker group. To do so, a copper(I) catalyzed alkyne-azide cycloaddition was carried out. There- fore, copper(II) sulfate was employed, which was in situ reduced by sodium ascorbate to form the active copper(I) species. The necessary ferrocene azide educt was synthesized in one step from bromoferrocene according to Plazuk et al.[211] The purification of the crude Click-reaction product however was not fully successful even after column chromatography. Nevertheless, the formation of bis(3,5-dimethyl-4-(1-ferrocenyl-1,2,3-triazol- 4-yl)pyrazol-1-yl)methane (bdmfctpzm) (55) could be verified by NMR spectroscopy and mass spectrometry and the properties of the ferrocene moieties could be determined via cyclic voltammetry (see figure 3.23).

N N N3 + Fe N N 15

CuSO4 sodium ascorbate

Fe N N N N Fe N N N N N N 55

Scheme 3.52: Synthesis of fcbdmtpz (55).

Compared to bedmpzm (15) the signals of the methyl groups in 55 are slightly shifted down ﬁeld to 2.37 and 2.73 ppm, respectively. The ferrocenyl protons split up into three signals. The unsubstituted cyclopentadienyl rings show a chemical shift of 4.23 ppm whereas the protons of the substituted rings can be found at 4.28 for the β and 4.87 ppm for the α protons. This conﬁrms the product formation since the corresponding signals of azidoferrocene are located at 4.05 and 4.29 ppm. The methylene bridge is detected at 6.25 ppm. Another proof for the successful product formation is the presence of a triazole proton peak at 7.69 ppm.

135 3 Results and Discussion

The 13C NMR spectrum of compound 55 shows the signals of the methyl groups at 11.0 and 13.4 ppm. The bridging methylene group can be found at 60.8 ppm. The ferrocenyl moieties are detected at 62.1, 66.7, 70.1 and 93.7 ppm. The carbon atoms of the triazole rings exhibit chemical shifts of 109.7 and 119.7 ppm. Finally, the signals of the pyrazole rings are found at 139.0, 141.1 and 146.8 ppm.

0.1 V/s -5

1.5x10

0.2 V/s

0.3 V/s

-5

1.0x10

0.4 V/s

0.5 V/s

-6

5.0x10

0.0 I (A) I

-6

-5.0x10

-5

-1.0x10

-5

-1.5x10

-0.5 -0.4 -0.3 -0.2 -0.1 0.0 0.1 0.2 0.3

U (V) vs Fc/Fc

Figure 3.23: Cyclic voltammogram of bdmfctpzm (55) in acetonitrile under nitrogen ◦ −4 atmosphere at 25 C. Conditions: 55: 5 × 10 mol/L, [NBu4][PF6]: 0.1 mol/L, scan rates: 0.1 V/s, 0.2 V/s, 0.3 V/s, 0.4 V/s, 0.5 V/s; * interal ferrocene standard.

The cyclic voltammogram features one reversible redox process. The oxidation potential of compound 55 could be determined to +201 mV and the reduction potential to +144 mV versus Fc/Fc+. Therefore the half wave potential of the ferrocene moieties lies with 173 mV versus Fc/Fc+ signiﬁcantly higher then the one observed for pure ferrocene. Those values agree well with comparable compounds in which ferrocene is attached to triazole rings.[68] A lower potential would however be desirable considering the potential application as a model complex for Rieske dioxygenases (see 1.4). Under the applied conditions, no electrochemical communication between the two ferrocenyl moieties could be observed.

136 3.4 Ferrocene Based Models for Rieske Dioxygenases

3.4.10 Bis(3,5-dimethyl-4-(1-methylferrocenyl-1,2,3-triazol-4- yl)pyrazol-1-yl)methane (bdmfcmtpzm) (56)

The second model compound, which was accessible from 15 via a Click reaction, was derived from azidomethylferrocene. The additional methylene bridge between the ferrocene moieties and the triazole rings was used to lower the inﬂuence of the triazoles on the potential of the ferrocenes, thus leading to a more desirable potential compared to compound 55. The necessary precursor azidomethylferrocene was synthesized from ferrocene in two steps via the ferrocenemethanol intermediate.[212,213] The reaction was carried out under similar conditions as the synthesis of 55, using copper(II) sulfate and sodium ascorbate to create the active copper(I) in situ as typical for CuAAC reactions. After puriﬁcation via column chromatography, bis(3,5-dimethyl-4- (1-methylferrocenyl-1,2,3-triazol-4-yl)pyrazol-1-yl)methane (bdmfcmtpzm) (56) could be obtained as an orange powder.

N3 N N + Fe N N 15

CuSO4 sodium ascorbate

N N N N N N N N Fe N N Fe 56

Scheme 3.53: Synthesis of bdmfcmtpzm (56).

The NMR spectra of bdmfcmtpzm (56) show similar chemical shifts as observed for bdmfctpzm (55). Successful product formation can be conﬁrmed due to the existence of a signal for the triazole protons in the 1H NMR spectrum at 7.37 ppm. The methylene bridge at the ferrocenyl moieties is detected at 5.30 ppm. The signals of the cyclopentadienyl rings are shifted to 4.16 ppm for the unsubstituted rings and 4.27 ppm for the α protons as well as 4.20 ppm for the β protons of the substituted rings. The 13C NMR spectrum contains a signal for the methylene bridge of the ferrocenyl moieties at 49.9 ppm. The cyclopentadienyl carbon atoms can be found at 68.7, 68.8, 68.9 and 81.1 ppm, followed by the signals of the triazole rings at 109.9 and 119.7 ppm,

137 3 Results and Discussion which give strong evidence of the success of the synthesis.

-5

2.5x10

0.1 V/s

-5

0.2 V/s 2.0x10

0.3 V/s

-5

1.5x10

0.4 V/s

0.5 V/s

-5

1.0x10

-6

5.0x10

0.0 I (A) I

-6

-5.0x10

-5

-1.0x10

-5

-1.5x10

-5

-2.0x10

-0.5 -0.4 -0.3 -0.2 -0.1 0.0 0.1 0.2 0.3

U (V) vs Fc/Fc

Figure 3.24: Cyclic voltammogram of bdmfcmtpzm (56) in acetonitrile under nitrogen ◦ −4 atmosphere at 25 C. Conditions: 56: 5 × 10 mol/L, [NBu4][PF6]: 0.1 mol/L, scan rates: 0.1 V/s, 0.2 V/s, 0.3 V/s, 0.4 V/s, 0.5 V/s.

The cyclic voltammogram of compound 56 shows a reversible redox process. The oxidation potential lies at +60 mV and the reduction potential at −9 mV versus Fc/Fc+. The half wave potential of the process can therefore be calculated to +26 mV. The inﬂuence of the methylene bridge decreased the potential by 147 mV, providing a way more beneﬁcial redox potential concerning the application as a model for Rieske dioxygenases. As a drawback, the conjugation towards the binding site of the ligand is interrupted by the additional methylene bridge. A single crystal suitable for X-ray structure determination could be obtained by layering a solution of compound 56 in ethyl acetate with n-hexane. Selected bond lengths and angles are listed in table 3.12. The molecular structure is depicted in 3.25. The compound crystallized in the triclinic space-group P−1. It was found that the triazole rings are slightly twisted out of plane compared to the pyrazole rings with dihedral angles of 18.172(1005)◦ and 3.77(102)◦. The angles between the triazole units and the ferrocenyl moieties amount to 112.2(5)◦ and 115.5(7)◦. The dihedral angle between the triazole rings and the link to the ferrocenyl units are 6 (N14-N15-C18-C30) = 55.344(740)◦ and

138 3.4 Ferrocene Based Models for Rieske Dioxygenases

Figure 3.25: Crystal structure of bdmfcmtpzm (56). Thermal ellipsoids are drawn at the 50 % probability level. Hydrogen atoms have been omitted for clarity.

6 (N24-N25-C28-C40) 50.995(908)◦, respectively. However, as the NMR spectra indicate free rotation of these groups, those angles are probably caused by crystal packing eﬀects. The angle at the methylene bridge between the pyrazoles amounts to 6 (N12-C1-N22) = 112.3(5)◦.

Distances (Å) C1-N12 1.451(7) C1-N22 1.449(8) N11-N12 1.357(7) N21-N22 1.368(7) N11-C12 1.344(8) N12-C14 1.360(8) N21-C22 1.323(8) N22-C24 1.355(9) N15-C18 1.491(7) N25-C28 1.459(9) C18-C30 1.487(10) C28-C40 1.492(10)

Angles (deg) N12-C1-N22 112.3(5) C1-N22-N21 117.9(5) C1-N12-N11 118.2(5) N15-C18-C30 112.2(5) N25-C28-C40 115.5(7) N13-C16-C13-C14 18.172(1005) N23-C26-C23-C24 3.77(102) N14-N15-C18-C30 55.344 (740) N24-N25-C28-C40 50.995(908)

Table 3.12: Selected interatomic distances (Å) and angles (deg) for compound 56.

A comparison to the molecular structure of bis(4-ferrocenyl-3,5-dimethylpyrazol-1-yl)- methane reported by Tampier and Bleifuss shows very similar bond lengths and angles as far as the bispyrazolyl backbone of the ligands is concerned.[71] Therefore, the additional triazole linker has most likely no signiﬁcant inﬂuence on the coordination properties of this N,N chelate ligand.

139 3 Results and Discussion

3.4.11 Summary of the Ferrocene Based Models for Rieske Dioxygenases

As was stated in the last section, optimization of the half wave potential for the examined compounds bepfcdmpzm (53) and mbepfcpzac (54) by the addition of the +I-eﬀect of methyl groups in pyrazole position 3 and 5, seems to be of minor importance for this system.

Compound Eox in mV Ered in mV E1/2 in mV befcpzm (51) +170 +83 +127 mbefcpzac (52) +176 +83 +130 bepfcdmpzm (53) +47 −30 +9 mbepfcpzac (54) +68 −15 +27 bdmfctpzm (55) +201 +144 +173 bdmfcmtpzm (56) +60 −9 +26 bfcdmpzm[71] +33 −50 −9 bfcpzm[71] +42 +42 0 bfcdmpzk[71] +37 −56 −9 bfcpzk[71] +103 +4 +54

Table 3.13: Summary of the electrochemical properties of the synthesized ferrocenyl derivatives and selected known ferrocenyl pyrazolyl compounds[71] (arithmetic means of 0.1- 0.5 V/s, versus Fc/Fc+).

Taking into account, that the methyl carboxylate moiety at the bridging carbon atom only leads to a slight shift of the potential by 3 mV for the compounds befcpzm (51) and mbefcpzac (52), the estimated change caused by the methyl groups calculates to only 15 mV.

R R R O R

N N N N N N N N Fe Fe Fe Fe R R R R R = H bfcpzm R = H bfcpzk R = CH3 bfcdmpzm R = CH3 bfcdmpzk

Figure 3.26: Ferrocenylpyrazole based ligands according to S. Tampier.[71]

As can be seen in table 3.13, this inﬂuence is much stronger for keto based ligands as bfcdmpzk and bfcpzk (for structures see ﬁgure 3.26). There, the presence of the methyl groups shifts the potential by 63 mV to more negative values.[71] However, without such

140 3.4 Ferrocene Based Models for Rieske Dioxygenases strong electron withdrawing bridging groups, this point seems to be only of minor importance. Thus the choice of the ferrocenyl moiety in the selected system is the more important task for the synthesis of such model complexes. As can be seen in table 3.13, the half wave potentials of the ligands that could be obtained so far range from +173 to +9 mV. It seems very likely that these values can be improved further towards lower redox potentials by a careful choice of ferrocenyl precursors.

R I R I

N R N R + K R N R N BH N N N N R N N R I I N N (i)R (ii) R I R I R R NH I N R (iii) O R R R N Rx N N N I I Fe N N R R R Scheme 3.54: Possible further ligands based on the presented synthetic route; conditions: (i) CHCl3/Base, (ii) KBH4, (iii) COCl2.

In contrast to the attempts of Tampier et al. to obtain N,N,O coordinating scorpionate ligands based on 4-ferrocenylpyrazole (see ﬁgure 3.26),[71] such compounds should now be accessible. Based on the presented results, the use of the ester groups to avoid unwanted interference of the carboxylate functions allows Sonogashira reactions to design various scorpionate ligands. Following this synthetic concept, a variation of the ligand backbone might be possible as well, as depicted in scheme 3.54. A ligand precursor is thereby synthesized as the corresponding 4-iodo-1H -pyrazolyl derivative and then subsequently reacted in a Sono- gashira reaction with any desired ethynyl-ferrocene moiety. Several routes to access various tripodal ligands are well established scorpionate chemistry.[1,23] E.g. the application of the one pot synthesis reported by Elflein et al. for the reaction of pyrazoles with aldehydes to obtain even more binding motifs should be possible as well.[23]

141 142 4 Summary and Outlook

143 4 Summary and Outlook

In order to overcome one of the most important drawbacks of bis(pyrazol-1-yl)acetic acids, namely their tendency to form bisligand complexes, they were modiﬁed following various concepts, so far. Apart from an increase of the sterical demand, vinyl linkers were introduced, to make the ligand capable to undergo copolymerization reactions. The most recent ligand of this type is the bis(3,5-dimethyl-4-vinylpyrazol-1-yl)acetic acid (Hbd- mvpza), which was ﬁrst reported on in 2010.[12,33–35] So far, complexes of this ligand and its copolymers were not employed in catalytic studies in order to compare their reactivity in their copolymerized state.

N N N N Cl O O N N N N Mo Mo Cl O Cl O O O 3 5

Figure 4.1: DMSO reductase model compounds 3 and 5.

Therefore, two complexes based on this ligand system were synthesized (see ﬁgure 4.1), one with a N,N (3) and one with a N,N,O coordination motif (5). These oxomolybdenum compounds showed good reactivity concerning the oxygen atom transfer (OAT) reaction from dimethyl sulfoxide to triphenylphosphine. Thus, these complexes might serve as functional model complexes for DMSO reductases.

Catalyst ligand/complex monomer copolymer

P10 MoO2Cl2(bdmvpzm) (3) MMA

P11 MoO2Cl2(bdmvpzm) (3) EGDMA

P12 MoO2Cl(bdmvpza) (5) MMA

P13 MoO2Cl(bdmvpza) (5) EGDMA P6-Mo bdmvpzm MMA P7-Mo bdmvpzm EGDMA P8-Mo Hbdmvpza MMA P9-Mo Hbdmvpza EGDMA

Table 4.1: Composition of copolymers employed in catalytic DMSO reduction.

In order to investigate the properties of the corresponding copolymers, both complexes were copolymerized with MMA and EGDMA (P10 - P13), respectively. Apart from this, copolymers of the two ligands with MMA and EGDMA were synthesized and subsequently loaded with molybdenum fragments (P6-Mo - P9-Mo). All of the obtained molybdenum containing polymers were analyzed via atomic absorption spectroscopy concerning the

144 molybdenum contents. It was found, that, in the case of the copolymerized complexes P10 - P13, the amount of incorporated complex fragments depends strongly on the applied copolymer. The reactivity of MMA during the polymerization reaction was found to be lower than the reactivity of the complex molecules, due to not being a crosslinker. The complex incorporation of up to 0.646 mmol/g was therefore rather high. The crosslinking EGDMA monomer on the other hand led to copolymers with metal contents of only up to 0.0334 mmol/g. When the polymers of the ligands were charged with the molybdenum fragments (P6- Mo - P9-Mo), the properties of the two copolymers also led to diﬀerent results. The highly crosslinked EGDMA copolymers reached occupation levels of up to 14.8 % while the less crosslinked MMA copolymers contained metal fragments in up to 78.5 % of the available binding sites. The amount of binding sites was thereby determined by the nitrogen value of the elemental analysis of the respective copolymers. The coordination motif of the incorporated complex moieties were investigated via IR spectroscopy and remained unchanged in either case when compared to the free complexes. The results of the catalytic DMSO reduction of the obtained compounds are summarized in table 4.2. As can be seen, all of the applied catalysts were able to catalyze the reduction of dimethyl sulfoxide under oxidation of triphenylphosphine.

−5 −1 Catalyst t [h] yield of OPPh3 [%] TON TOF [10 s ] 3 6 56 112 519 5 6 55 110 509 P10 24 87 174 201 P11 24 1 2 2.31 P12 24 36 72 83.3 P13 24 24 48 55.6 P6-Mo 24 89 178 206 P7-Mo 24 71 142 164 P8-Mo 24 44 88 102 P9-Mo 24 8 16 18.5

Table 4.2: Results of catalytic DMSO reduction (ncatalyst = 7.50 µmol, 0.5 mol%; nPPh = 1.50 mmol).

In general, the MMA copolymers exposed higher catalytic activities than the corresponding EGDMA derivatives, which is caused by the better access to the metal centers. It was also obvious that in the latter, the polymers which were charged with metal fragments subsequently to the polymerization process showed a signiﬁcantly higher activity. Their counterparts, for which the ﬁnal complexes were copolymerized probably contain a

145 4 Summary and Outlook certain amount of metal sites, which were locked in and therefore blocked from substrate access during the polymerization. Since the EGDMA polymers are highly crosslinked in comparison to the MMA copolymers, the eﬀect there is more striking (compare P11 and P7-Mo). In future experiments, such eﬀects could be avoided by the application of molecular imprinting. Therefore, a dummy substrate can be bound to the active site prior to the copolymerization process, which is removed afterwards. By this way, a cavity might be created, which would possibly keep the active site accessible for substrates in catalytic studies. The second part of this thesis dealt with the synthesis of ligands bearing an acetylene instead of a vinyl linker group in position 4 of the pyrazole rings. As such, a Hbdmpza derivative as well as bis(pyrazolyl)methane derivatives were synthesized (see scheme 4.1).

HO O

N N N N N N N N 15 29

HN TMS N 28

N N OH

N N N N N N N N 34 32

Scheme 4.1: 4-Ethynylpyrazole based scorpionate ligands.

Apart from bis(4-ethynyl-3,5-dimethylpyrazol-1-yl)methane (bedmpzm) (15), which was initially synthesized under Corey-Fuchs conditions starting from bis(3,5-dimethyl-4- formylpyrazol-1-yl)methane (1), these ligands were synthesized starting from 3,5-dimethyl- 4-(trimethylsilyl)ethynylpyrazole (28). This compound was synthesized from 3,5-dimethylpyrazole in four steps. Starting from there, 15 could also be synthesized under phase transfer conditions. The well established one pot synthesis of bispyrazolylacetic acids by

146 Burzlaff et al. was used in the synthesis of the Hbdmpza derivative 29.[11] Due to the basic conditions of this reaction, the trimethylsilyl groups are removed during the synthesis without an additional step. Bis(4-ethynylpyrazol-1-yl)methane ligands on the other hand were also obtained following a one pot synthesis procedure established by Elflein et al.[23] Following this protocol, basically any desired aldehyde can be used as bridging group thus altering the coordination motif. In this thesis, salicylaldehyde as well as 1-methyl-2-imidazolecarboxaldehyde were used to obtain the corresponding N,N,O and N,N,N coordinating ligands 30 and 33. The protecting trimethylsilyl group was kept in place during the reaction and could be removed in an additional step under either basic conditions or the application of potassium ﬂuoride in methanol. The introduction of acetylene linkers allows for a range of reactions to further modify the ligands or complexes thereof as depicted in scheme 4.2. Included are coupling reactions like the Glaser homo coupling reaction or the Cadiot-Chodkiewicz hetero coupling reaction. Furthermore, modiﬁcations via Click chemistry (CuAAC) or Sonogashira reactions are feasible.

HN R' N

R' Br

HN N N R' N HN R' I HN 3 R' N N N N R'

HN N

HN N N NH

Scheme 4.2: Possible reactions of the acetylene linker groups of 3,5-dimethyl-4-ethynylpyrazole.

Possible applications are manifold. Besides the herein presented modifications to serve as model complexes for Rieske dioxygenases, the introduction of fluorophores could be beneficial. The fluorescence could be switched via paramagnetic fluorescence quenching

147 4 Summary and Outlook induced by metal centers coordinated to the ligand. Another possible application is the PEGylation of the ligand. Thereby, polyethylene glycol polymer (PEG) chains are attached to the ligand molecules to improve their solubility. This can be achieved by the methods mentioned above, since a wide range of PEG derivatives are commercially available. This process is well established in pharmaceutical chemistry, since water solubility can be greatly improved without increasing the toxicity of the corresponding drugs.[197] Starting from 3,5-dimethyl-4-(trimethylsilyl)ethynyl-1-tritylpyrazole (26), the N,N coordinating ligand 1,4-bis(3,5-dimethyl-1H -pyrazol-4-yl)butadiyne (37) could be obtained, which is suitable to synthesize 1D coordination polymers. Therefore, the trimethylsilyl protecting group was removed to allow a Glaser homo coupling reaction of the obtained compound. A trityl protecting group was applied for this purpose. This group protects the nitrogen donors from building such polymers with the metal catalysts used during the coupling reaction.

Figure 4.2: Molecular structure poly(cobalt(II)acetylacetonato-bis(1,4-bis(3,5-dimethyl- 1H-pyrazol-4-yl)butadiyne)) (39)

The deprotected ligand readily forms coordination polymers with metal salts. As such, cobalt acetylacetonato and cobalt chloride coordination polymers could be obtained. It was possible to determine the structure of the cobalt(II)acetylacetonato polymer (38) via X-ray structure determination as it is depicted in ﬁgure 4.2. Furthermore, in order to design model systems for Rieske dioxygenases several ligands bearing ferrocenyl moieties were synthesized. These model systems were on the one hand based on the above mentioned bis(4-ethynyl-3,5-dimethylpyrazol-1-yl)methane (bedmpzm) (15) and on the other hand on 4-iodo substituted bis(pyrazolyl)methanes (45, 46) and -acetic acid (49). These ligand backbones were reacted with several ferroncenyl precursors in copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) or Sonogashira

148 O O

N N N N Fe 54 Fe

N N N N N N N N Fe N N Fe 56

Figure 4.3: Examples of Rieske dioxygenase models presented in this thesis. reactions. The influence of different linker groups on the electrochemical potential of the resulting compounds was investigated via cyclic voltammetry. This procedure revealed for each of the examined compounds one reversible redox potential. The obtained half wave potentials are summarized in table 4.3. In order to mimic the behavior of ferredoxin clusters, a potential of −150 up to +400 mV vs. SHE would be desirable, what equates to −550 to 0 mV vs. the ferrocene/ferrocenium couple. As can be seen in table 4.3, the most promising candidates are those with an additional phenyl group in the linker moiety. In combination with the N,N,O binding motif of bis(pyrazolyl)acetic acids, which mimics the natural 2-His-1-carboxylate triad binding motif of Rieske dioxygenases, these ligands are promising candidates for model complexes. However, it was shown, that the potential of such compounds can be tuned over a relatively wide potential range, which leaves room for future optimizations. Due to the versatility of this concept, different ferrocenyl derivatives can be introduced as electron donors easily.

Table 4.3: Summary of the electrochemical properties of the synthesized ferrocenyl derivatives (versus Fc/Fc+).

149 4 Summary and Outlook

For the studies conducted herein, the carboxylate donor function was protected by a esteriﬁcation. In future studies, iron(II) centers need to be coordinated subsequent to saponiﬁcation of the ester group, to create structural and functional models of a Rieske center.

150 5 Zusammenfassung und Ausblick

151 5 Zusammenfassung und Ausblick

Bis(pyrazol-1-yl)essigsäure Liganden wurde in den letzten 15 Jahren auf verschiedenste Weise modiﬁziert, um das Problem der Bisligandkomplexbildung zu vermeiden. Abgese- hen von der Erhöhung des sterischen Anspruchs wurden z.B. Vinyllinker eingeführt, die den Liganden befähigen, Vinylgruppen-basierte Copolymerisationsreaktionen einzugehen. Der jüngste Ligand dieser Art ist Hbdmvpza, welcher 2010 publiziert wurde.[12,33–35] Bisher wurden Komplexe dieses Liganden und seiner Copolymere nicht in katalytischen Studien eingesetzt, bei denen ihre jeweilige Reaktivität im copolymerisierten Zustand verglichen wurde.

N N N N Cl O O N N N N Mo Mo Cl O Cl O O O 3 5

Abbildung 5.1: Modellverbindungen 3 und 5 für DMSO-Reduktasen.

Aus diesem Grund wurden auf Grundlage dieses Ligandsystems zwei Komplexe synthetisiert (siehe Abbildung 5.1): einer von ihnen mit einem N,N (3) und einer mit einem N,N,O Koordinationsmotiv (5). Diese Oxomolybdän Verbindungen zeigten gute Reak- tivität im Bezug auf die Sauerstoﬀtransfer (OAT) Reaktion von Dimethylsulfoxid auf Triphenylphosphan. Daher eignen sie sich für den Einsatz als Modelsysteme für DMSO- Reduktasen.

Katalysator Ligand/Komplex-Monomer Copolymer

P10 MoO2Cl2(bdmvpzm) (3) MMA

P11 MoO2Cl2(bdmvpzm) (3) EGDMA

P12 MoO2Cl(bdmvpza) (5) MMA

P13 MoO2Cl(bdmvpza) (5) EGDMA P6-Mo bdmvpzm MMA P7-Mo bdmvpzm EGDMA P8-Mo Hbdmvpza MMA P9-Mo Hbdmvpza EGDMA

Tabelle 5.1: Zusammensetzung der Copolymere für die katalytische DMSO-Reduktion.

Um die Eigenschaften der jeweiligen Copolymere zu überprüfen wurden beide Komplexe jeweils mit MMA und EGDMA copolymerisiert (P10 - P13). Darüber hinaus wurden die metallfreien Liganden ebenfalls mit MMA und EGDMA polymerisiert und nachträglich mit Molbydän beladen (P6-Mo - P9-Mo). Alle erhaltenen molybdänhaltigen Polymere

152 wurden, nachdem sie chemisch aufgeschlossen wurden, mittels Atomabsorptionsspektros- kopie bezüglich des Molybdängehaltes analysiert. Die Ergebnisse zeigten, dass im Fall der copolymerisierten Komplexe P10 - P13 die Menge an eingebetteten Komplexfragmenten stark vom eingesetzten Copolymer abhängig ist. Die Reaktivität von MMA im Bezug auf die Polymersationsreaktion erwies sich als niedriger als die der Komplexmoleküle, da es sich bei MMA um keinen Quervernetzer handelt. Dadurch erklärt sich der hohe Gehalt an Komplexfragmenten im Copolymer von bis zu 0.646 mmol/g. Im Gegensatz dazu führte der Einsatz des quervernetzenden EGDMA nur zu Metallgehalten von bis zu 0.0334 mmol/g.

-5 -1 Katalysator t [h] Ausbeute an OPPh3 [%] TON TOF [10 s ] 3 6 56 112 519 5 6 55 110 509 P10 24 87 174 201 P11 24 1 2 2.31 P12 24 36 72 83.3 P13 24 24 48 55.6 P6-Mo 24 89 178 206 P7-Mo 24 71 142 164 P8-Mo 24 44 88 102 P9-Mo 24 8 16 18.5

Tabelle 5.2: Ergebnisse der katalytischen DMSO Reduktion (ncatalyst = 7.50 µmol, 0.5 mol%; nPPh = 1.50 mmol).

Wurden die Copolymere der freien Liganden nachträglich mit Molybdän beladen (P6-Mo - P9-Mo), führten die unterschiedlichen Eigenschaften der beiden Copolymere ebenfalls zu voneinandner abweichenden Ergebnissen. Die stark quervernetzten EGDMA Copoly- mere erreichten einen Besetzungsgrad von bis zu 14.8 %, während die weit weniger quervernetzten MMA Copolymere an bis zu 78.5 % der verfügbaren Bindungsstellen Metallfrag- mente enthielten. Die Anzahl der verfügbaren Bindungsstellen wurden dabei über den Stickstoﬀgehalt der Elementaranalyse der jeweiligen Polymere bestimmt. Das Koordina- tionsmotiv der eingebetteten Metallfragmente wurde mittels IR-Spektroskopie untersucht und erwies sich in beiden Fällen als unverändert im Vergleich zu den freien Komplexen. Die Ergebnisse der katalytischen Reduktion von DMSO durch die erhaltenen Verbindun- gen sind in Tabelle 5.2 zusammengefasst. Es ist ersichtlich, dass alle verwendeten Kataly- satoren Aktivität im Bezug auf die katalytische Reduktion von Dimethylsulfoxid unter Oxidation von Triphenylphosphan zeigten. Im Allgemeinen zeigten die MMA basierten Copolymere eine höhere katalytische Aktiv- ität als die entsprechenden EGDMA Polymere, da diese leichter einen Zugang zu den

153 5 Zusammenfassung und Ausblick

Metallfragmenten erlauben. Weiterhin wurde klar, dass bei letzteren die Polymere, die nach der Polymerisation mit Metallfragmenten beladen wurden, eine erhöhte Aktivität zeigten. Deren Gegenstücke, bei denen der bereits koordinierte Komplex copolymerisiert wurde, enthielten vermutlich eine gewisse Anzahl an Metallzentren, zu denen der Zu- gang für Substrate durch den Polyermisationsvorgang blockiert wurde. Dieser Eﬀekt ist hier besonders stark, da EGDMA Polymere im Vergleich zu MMA-Polymeren wesentlich stärker quervernetzt sind (vergleiche P11 und P7-Mo). In zukünftigen Versuchen könnte dieser Eﬀekt durch molecular imprinting vermieden werden. Hierbei wird ein Dummy-Substrat vor der Polymerisation an das reaktive Zentrum gebunden und anschließend wieder entfernt. Auf diese Weise wird ein Hohlraum erzeugt, der dazu führt, dass das aktive Zentrum des Komplexes für Substratmoleküle zugänglich bleibt. Der zweite Teil dieser Arbeit beschäftigte sich mit der Synthese von Liganden, welche mit einer Acetylengruppe anstelle der Vinylgruppe an Position 4 des Pyrazolrings substituiert sind. Als solche wurde ein Hbdmpza-Derivat sowie Bis(pyrazol-1-yl)methan Liganden dargestellt (siehe Schema 5.1).

HO O

N N N N N N N N 15 29

HN TMS N 28

N N OH

N N N N N N N N 34 32

Schema 5.1: 4-Ethinylpyrazol-basierte Skorpionatliganden.

Mit Ausnahme von Bis((4-ethinyl)-3,5-dimethylpyrazol-1-yl)methan (bedmpzm) (15), welches unter Corey-Fuchs Bedingungen ausgehend von Bis(3,5-dimethyl-4-formylpyrazol-

154 1-yl)methan (1) synthetisiert wurde, wurden diese Liganden ausgehend von 3,5-Dimethyl- 4-(trimethylsilyl)ethinylpyrazol (28) dargestellt. Diese Verbindung wurde ausgehend von 3,5-Dimethylpyrazol in vier Schritten erhalten. Mit diesem Edukt konnte 15 ebenfalls unter Phasentransferbedingungen dargestellt werden. Für die Synthese der entsprechenden Bis(pyrazolyl)essigsäure 29 wurde die bekannte Eintopfsynthese für Bispyrazoly- lessigsäuren angewendet, die von Burzlaff et al. 2001 etabliert wurde.[11] Aufgrund der basischen Reaktionsbedingungen dieser Reaktion, wurden die Trimethylsilylschutz- gruppen ohne weitere Reaktionsschritte im Lauf der Synthese entfernt. Die Bis(4-ethinylpyrazol-1-yl)methan Liganden wurden ebenfalls mittels einer Eintopfsyn- these erhalten. In diesem Fall mittels der Eintopfsynthese für enantionmerenreine Het- eroskorpionat Liganden, die bereits vielfach im Arbeitskreis Anwendung fand.[23] Mittels dieser Reaktion können prinzipiell verschiedenste Aldehyde als Brückengruppen eingesetzt und damit das Koordinationsmotiv beliebig angepasst werden. Im Rahmen dieser Arbeit wurden Salicylaldehyd sowie 1-Methyl-2-imidazol-carboxaldehyd verwendet um die entsprechenden N,N,O und N,N,N koordinierenden Liganden darzustellen. Die Trimethyl- silylschutzgruppen blieben hierbei intakt und konnten in einem weiteren Schritt unter Verwendung einer Base oder durch Kaliumﬂuorid entfernt werden.

HN R' N

R' Br

HN N N R' N HN R' I HN 3 R' N N N N R'

HN N

HN N N NH

Schema 5.2: Mögliche Reaktionen der Acetylen-Linker-Gruppen für 3,5-Dimethyl-4- ethinylpyrazol.

Die Einführung von Acetylen-Linkern erlaubt eine ganze Reihe von Reaktionen, mit deren Hilfe die Liganden oder deren Komplexe weiter modiﬁziert werden können, wie in Schema

155 5 Zusammenfassung und Ausblick

5.2 dargestellt. Unter diesen sind Reaktionen wie die Glaser Homokupplungsreak- tion, sowie die Cadiot-Chodkiewicz-Reaktion als Heterokupplungsreaktion. Darüber hinaus können weitere Schritte in Form von Click-Chemie-Reaktionen (CuAAC) oder Sonogashira-Kupplungen durchgeführt werden. Die dadurch enstehenden Anwendungsmöglichkeiten sind vielfältig. Abgesehen von den hier vorgestellten Modellliganden für Rieske Dioxygenasen (s.u.), wäre die Einführung von Fluoreszensgruppen ein lohnendes Ziel. Die Fluoreszens könnte hierbei durch para- magnetisches Fluoreszensquenching, ausgelöst von an das aktive Zentrum des Liganden koordinierten Metallen, gesteuert werden. Eine weitere Anwendungsmöglichkeit besteht in der PEGylierung des Liganden. Hierbei werden Polyethylenglycol-Polymer-Stränge (PEG) mit dem Liganden verbunden um ihre Löslichkeit zu verbessern. Dies kann durch die oben genannten Methoden durchgeführt werden, da eine breite Auswahl an PEG-Derivaten kommerziell verfügbar ist. Dieser Prozess wird insbesondere in der phar- mazeutischen Chemie häuﬁg angewendet, um die Wasserlöslichkeit von Substanzen stark zu erhöhen, ohne dabei die Toxizität der jeweiligen Verbindungen zu erhöhen.[197]

Abbildung 5.2: Molekülstruktur von Poly(cobalt(II)acetylacetonato-bis(1,4-bis(3,5- dimethyl-1H-pyrazol-4-yl)butadiin)) (39).

Ausgehend von 3,5-Dimethyl-4-(trimethylsilyl)ethinyl-1-tritylpyrazol (26), welches ein Zwis- chenprodukt bei der Synthese oben genannter Liganden ist, war es darüber hinaus möglich, einen Ligand mit Anwendungsmöglichkeiten für 1D-Koordinationspolymere darzustellen. Dafür wurde die Trimethylsilylschutzgruppe entfernt, um eine Glaser Homokupplung zu ermöglichen. Eine Tritylschutzgruppe wurde hierbei eingesetzt, um die vorzeitige Bildung von Polymeren mit dem Metallkatalysator der Kupplungsreaktion zu verhindern. Der entschützte Ligand bildete leicht Koordinationspolymere mit Metallsalzen, nachdem die Tritylschutzgruppen entfernt wurden. Es konnten Koordinationspolymere von

156 O O

N N N N Fe 54 Fe

N N N N N N N N Fe N N Fe 56

Abbildung 5.3: Auswahl von im Rahmen dieser Arbeit dargestellten Rieske- Dioxygenase-Modellen.

Kobalt(II)acetylacetonat und Kobalt(II)chlorid erhalten werden. Die Struktur des Ko- balt(II)acetylacetonat Polymers konnte mittels Röntgenstrukturanalyse aufgeklärt werden, wie in Schema 5.2 dargestellt.

Im letzten Teil der Arbeit wurden mit dem Ziel Modellkomplexe für Rieske-Dioxygenasen aufzubauen Ferrocenyl substituierte Liganden synthetisiert. Diese Modellsysteme wurden einerseits ausgehend vom oben genannten Bis(4-ethinyl-3,5-dimethylpyrazol-1-yl)methan (bedmpzm) (15) und andererseits ausgehend von 4-Iodo-substituierten Bis(pyrazol-1- yl)methanen (45, 46) und -essigsäuren (49) dargestellt. Diese Liganden wurden mit verschiedenen Ferrocenylvorstufen in CuAAC oder Sonogashira Reaktionen umgesetzt. Der Einﬂuss verschiedener Linkergruppen auf das elektrochemische Potential der dabei erhaltenen Verbindungen wurde mittels zyklischer Voltammetrie bestimmt. Dabei wurde für alle untersuchten Substanzen ein reversibles Redoxpotential beobachtet. Die daraus errechneten Halbwellenpotentiale sind in Tabelle 5.3 zusammengefasst. Um das Verhal-

Verbindung Eox in mV Ered in mV E1/2 in mV befcpzm (51) +170 +83 +127 mbefcpzac (52) +176 +83 +130 bepfcdmpzm (53) +47 −30 +9 mbepfcpzac (54) +68 −15 +27 bdmfctpzm (55) +201 +144 +173 bdmfcmtpzm (56) +60 −9 +26

Tabelle 5.3: Zusammenfassung der elektrochemischen Eigenschaften der dargestellten Ferrocenylverbindungen (gegen Fc/Fc+).

157 5 Zusammenfassung und Ausblick ten natürlicher Ferredoxincluster nachbilden zu können, wird ein Potential zwischen −150 bis +400 mV gegen SHE benötigt, was einem Potential von −550 bis 0 mV gegen das Ferrocen/Ferrocenium-Redoxpaar entspricht. Wie aus Tabelle 5.3 ersichtlich, erwiesen sich die Verbindungen mit zusätzlichen Phenylresten in der Linkereinheit als die vielver- sprechendsten Kandidaten. In Kombination mit dem N,N,O Koordinationsmotiv der Bis(pyrazolyl)essigsäuren, welches die natürlich vorkommende 2-His-1-carboxylat Triade der Rieske Dioxygenasen nachzubilden vermag, stellen derartige Verbindungen einen vielversprechenden Ausgangspunkt für Rieske-Modellsysteme dar. Es wurde weiterhin gezeigt, dass das elektrochemische Potential solcher Verbindungen über einen relativ bre- iten Potentialbereich justierbar ist, was Raum für weitere Optimierungen lässt. Aufgrund der Vielseitigkeit dieser Herangehensweise, können weitere Ferrocenyleinheiten leicht als Elektronendonoren eingeführt werden. Für die hier durchgeführten Untersuchungen wurden die Carboxylatgruppen der Liganden durch Veresterung geschützt. In zukünftigen Versuchen müssen diese verseift und an Eisen(II)-Zentren koordiniert werden, um strukturelle und funktionelle Modellsysteme für Rieske-Zentren darstellen zu können.

158 6 Experimental Section

159 6 Experimental Section

6.1 General Remarks

6.1.1 Working Techniques

All air sensitive compounds were prepared under dry nitrogen atmosphere using con- ventional Schlenk techniques. Purchased solvents (p.a. grade, < 50 ppm H2O) were degassed prior to use and stored under nitrogen atmosphere.

6.1.2 Spectroscopic and Analytical Methods

NMR Spectra The 1H, 13C and 31P NMR spectra were recorded using a Bruker DPX300 AVANCE and a Bruker DRX400 WB spectrometer. The calibrations of the spectra were carried out on the signal of the deuterated solvent, tetramethylsilane or H3PO4. Multiplicities are marked as follows:

s singlet d doublet t triplet m multiplet

Infrared Spectroscopy

Infrared spectra were recorded with an Excalibur FTS-3500 in CaF2 cuvettes (0.2 mm) or as KBr pellets. The latter were prepared using a Perkin-Elmer hydraulic press (10 t/cm2). Relative absorption intensities were marked as follows:

vs very strong s strong m medium w weak br broad

Mass Spectra ESI-MS spectra were recorded with a Bruker Daltonics maXis ultrahigh resolution ESI- TOF mass spectrometer with a resolution of at least 40.000 FWHM. Peaks were identiﬁed using simulated isotopic patterns created within the Bruker Data Analysis software.

160 6.1 General Remarks

Elemental Analysis Elemental analyses were determined with an EURO EA 3000 (Euro Vector) and EA 1108 (Carlo Erba) instrument (σ = ± 1 % of the measured content).

Polymer analysis The amount of incorporated ligand moieties in the polymers was determined by the nitrogen content (% N) of the elemental analysis of the respective polymer using the following equation:

mmol Ligand % N = · 10 g P olymer 4 · 14 g · mol−1

Atomic absorption spectrometry (AAS) Atomic absorption spectrometry (AAS) was carried out using a Perkin-Elmer 5100 F-AAS with AS-90 sample automation. Method of calibration was standard addition. Wave- length/spectral band width in nm: 313.3 nm.

Sample Preparation for AAS

The samples of the according copolymers (50 mg) were suspended in H2SO4 (p.a., conc., 3.00 mL). The suspension was heated for 2 h at 140 ◦C in a 25 or 50 mL volumetric ﬂask.

The black solution was cooled down to room temperature and treated with H2O2 (35 wt.% solution in water). The mixture was heated to 140 ◦C for 12 h to give a clear colourless solution. After cooling to room temperature, further H2O2 (1.00 mL) was added and stirring was continued for 12 h at 140 ◦C. The solution was cooled to room temperature again and diluted to 25.0 respectivley 50.0 mL with nitric acid (2 wt.% solution in water) and analyzed by AAS.

Cyclic Voltammetry Cyclic voltammetry experiments were carried out using an AUTOLAB PGSTAT 100. A three electrode cell with a gold disk working electrode, a platinum wire counter electrode and a silver wire as pseudo-reference electrode was used. Cyclic voltammetry was performed in acetonitrile or dichloromethane containing 0.1 m [n-Bu4N]PF6 as supporting electrolyte. All solutions were deoxygenated with nitrogen before each experiment and a blanket of nitrogen was used to cover the solution during the experiment. The potential values (E) were calculated using the following equation: E = (Epc + Epa)/2, where Epc and Epa correspond to the cathodic and anodic peak potentials, respectively. Potentials are referenced to the ferrocene/ferrocenium (Fc/Fc+) couple, which was used as internal standard.[214]

161 6 Experimental Section

X-ray Structure Determination X-ray structure determinations were carried out with a Bruker-Nonius Kappa-CCD diffractometer and a Agilent Super Nova S2 CCD diffractometer. Single crystals were mounted with Paratone-N, glue or perfluorated oil on a glass fiber. The structures were solved by using direct methods and refined with full-matrix least-squares against F 2 (SHELX- 97).[215] A weighting scheme was applied in the last steps of the refinement with w = 2 2 2 2 2 1/[σ (Fo ) + (aP ) + bP ] and P = [2F c + max(Fo , 0)]/3. Most hydrogen atoms were included in their calculated positions and refined in a riding model.

6.1.3 Destabilization of Copolymers

In order to destabilize EGDMA and MMA, they were washed each three times with 5 % sodium hydroxide solution in order to remove the stabilizer. Afterwards, they were dried rigorously with sodium sulfate. The destabilized copolymers were stored at −30 ◦C.

6.1.4 Chemicals

The following chemicals were used as purchased without further puriﬁcation:

- azobisisobutyronitrile - 4-ethynylaniline

- benzyltriethylammonium chloride - ethynylferrocene

- bis(triphenylphosphine)palladium - ethylene glycol dimethacrylate dichloride - ferrocene - cer(IV) ammoniumnitrate - iodine - cobalt(II) bromide - manganese(II) chloride

- cobalt(II) chloride - 1-methyl-2-imidazolecarboxaldehyde

- cobalt(II) acetylacetonate - methyl methacrylate

- copper(II) acetate - molybdenum(VI) dichloride dioxide

- copper(I) iodide - n-butyllithium

- copper(II) sulfate - paraformaldehyde

- dibromoacetic acid - phosphorous oxychloride

- dichloroacetic acid - potassium ﬂuoride

- 3,5-dimethylpyrazole - potassium tert-butoxide

162 6.1 General Remarks

- pyrazole - triethylamine

- salicylaldehyde - triﬂuoroacetic acid

- sodium ascorbate - triphenylmethyl-phosphonium bromide - sodium azide - trimethylphosphane

- sodium hydride - trimethylsilylacetylene

- sodium nitrite - trityl chloride

- thionyl chloride - zinc(II) chloride

The following chemicals were synthesized according to literature procedures.

- azidomethylferrocene[212,213]

- bis(3,5-dimethyl-4-formylpyrazol-1-yl)methane (1)[44]

- bis(3,5-dimethylpyrazol-1-yl)methane[43]

- bis(3,5-dimethyl-4-vinylpyrazol-1-yl)acetic acid (4)[35]

- bis(3,5-dimethyl-4-vinylpyrazol-1-yl)methane (bdmvpzm) (2)[35]

- ferrocene azide[211]

- 1-ferrocenyl-4-ethynylbenzene[208,209]

- 4-iodopyrazole (22)[192]

- 4-iodo-3,5-dimethylpyrazole (23)[192]

- 4-iodo-3,5-dimethyl-1-tritylpyrazole (25)[71]

- 4-iodo-1-tritylpyrazole (24)[71]

163 6 Experimental Section

6.2 Oxo-Transfer Catalysis by Chelate and Scorpionate Oxomolybdenum Complexes

6.2.1 Synthesis of Bis(3,5-dimethyl-4-formylpyrazol-1-yl)methane (1)[44]

A solution of bis(3,5-dimethylpyrazol-1-yl)methane (8.96 g, 43.9 mmol) in dimethylformamide (100 mL) was heated to a temperature of 96 ◦C. Within one hour, phosphorus oxychloride (14.9 g, 96.6 mmol) was slowly added. The resulting solution was stirred over night at this temperature. After this time, the heating was removed and the solution was chilled to 0 ◦C under vigorous stirring. Subsequently, the reaction mixture was poured into ice water, what led to the formation of a precipitate. The latter was ﬁltered oﬀ and washed thoroughly with water to remove impurities. Finally, the product was dried in a desiccator.

O O N N N N

C11H16N4 MW: 204.28 g/mol

Yield: 2.88 (11.1 mmol, 26 %)

1 ◦ 5 3 H NMR (300 MHz, CDCl3, 25 C): δ = 2.41 (s, 6 H, C -CH3), 2.79 (s, 6 H, C -CH3),

6.11 (s, 2 H, -CH2-), 9.93 (s, 2 H, -CHO) ppm.

13 ◦ 5 3 C NMR (75.5 MHz, CDCl3, 25 C): δ = 10.1 (C -CH3), 12.7 (C -CH3), 59.1 (-CH2-), 118.8 (C4), 146.5 (C5), 151.8 (C3), 185.0 (-CHO) ppm.

164 6.2 Oxo-Transfer Catalysis by Chelate and Scorpionate Oxomolybdenum Complexes

6.2.2 Synthesis of Bis(3,5-dimethyl-4-vinylpyrazol-1-yl)methane (bdmvpzm) (2)[35]

A suspension of triphenylmethyl-phosphonium bromide (19.8 g, 55.4 mmol) in tetrahydrofuran was treated with potassium tert-butoxide (5.80 g, 51.6 mmol). The resulting mixture was stirred for one hour at room temperature. After this time, it was reacted with bis(3,5-dimethyl-4-formylpyrazol-1-yl)methane (1) (4.80 g, 18.4 mmol). The solution was heated to a temperature of 60 ◦C and stirred for two hours. After this time, the heating was removed and the stirring was continued overnight at room temperature. Sub- sequently all solids were filtered off and all volatiles were removed in vacuo. The remaining residue was dissolved in dichloromethane and purified via column chromatography (silica, n-pentane:ethyl acetate 7:3 v/v).

N N N N

C15H20N4 MW: 256.35 g/mol

Yield: 3.78 g (14.8 mmol, 80 %)

1 ◦ 5 3 H NMR (300 MHz, CDCl3, 25 C): δ = 2.27 (s, 6 H, C -CH3), 2.47 (s, 6 H, C -CH3), 2 3 2 5.14 (dd, J H,H = 1.4 Hz, J H,H = 11.6 Hz, 2 H, (Z)-H2C=), 5.29 (dd, J H,H = 1.4 Hz, 3 3 3 J H,H = 17.9 Hz, 2 H, (E)-H2C=), 6.09 (s, 2 H, -CH2-), 6.48 (dd, J H,H = 17.9 Hz, J H,H = 11.5 Hz, 2 H, -HC=) ppm.

13 ◦ 5 3 C NMR (75.5 MHz, CDCl3, 25 C): δ = 10.2 (C -CH3), 13.6 (C -CH3), 60.7 (-CH2-), 4 5 3 112.8 (=CH2), 116.5 (C ), 127.4 (-HC=), 138.0 (C ), 146.8 (C ) ppm.

165 6 Experimental Section

6.2.3 Synthesis of [MoO2Cl2(bdmvpzm)] (3) A solution of molybdenum(VI) dichloride dioxide (0.388 g, 1.95 mmol) in tetrahydrofuran was treated with bdmvpzm (1) (0.500 g 1.95 mmol). The resulting solution was stirred for one hour at room temperature, whereupon a yellow precipitate was formed. This precipitate was collected via ﬁltration and dried in vacuo. Crystals suitable for an X-ray structure determination could be obtained by layering a solution of 3 in dichloromethane with n-hexane.

N N Cl N N Mo Cl O O 3

C15H20Cl2MoN4O2 MW: 455.21 g/mol

Yield: 0.604 g (1.33 mmol, 68 %)

1 ◦ 5 3 H NMR (300 MHz, CDCl3, 25 C): δ = 2.15 (s, 6 H, C -CH3), 2.44 (s, 6 H, C -CH3), 2 3 2 5.09 (dd, J H,H = 1.2 Hz, J H,H = 11.6 Hz, 2 H, (Z)-H2C=), 5.26 (dd, J H,H = 1.2 Hz, 3 3 3 J H,H = 17.9 Hz, 2 H, (E-H2C=), 6.12 (s, 2 H, -CH2-), 6.50 (dd, J H,H = 17.9 Hz, J H,H = 11.7 Hz, 2 H, -HC=) ppm.

13 ◦ 5 3 C NMR (75.5 MHz, CDCl3, 25 C): δ = 9.69 (C -CH3), 13.5 (C -CH3), 59.0 (-CH2-), 4 5 3 112.3 (=CH2), 115.2 (C ), 127.6 (-HC=), 138.0 (C ), 145.8 (C ) ppm.

Elemental analysis of C15H20Cl2MoN4O2 (455.21 g/mol): calcd. C 39.58, H 4.43, N 12.31; found C 39.83, H 4.30, N 12.53 %.

−1 IR (KBr): νe = 944 (s, νsym(Mo=O)), 917 (s, νasym(Mo=O)) cm .

166 6.2 Oxo-Transfer Catalysis by Chelate and Scorpionate Oxomolybdenum Complexes

6.2.4 Synthesis of Bis(3,5-dimethyl-4-vinylpyrazol-1-yl)acetic acid (Hbdmvpza) (4)[35]

A solution of bdmvpzm (2) (3.75 g, 14.6 mmol) in tetrahydrofuran was cooled to −80 ◦C. At this temperature, n-butyllithium (1.6 m solution in n-hexane, 9.58 mL, 15.3 mmol) was added slowly under vigorous stirring. The resulting solution was allowed to warm to a temperature of −20 ◦C over the next four hours. After this time, a dry stream of carbon dioxide was passed through the reaction mixture for one hour. Subsequently, the vessel was allowed to slowly reach room temperature and stirred over night. Afterwards, all volatiles were removed and the remaining residue was dissolved in water (250 mL). The resulting aqueous phase was washed with diethyl ether (2 × 50 mL) in order to remove impurities. After acidiﬁcation to an pH value of 2 with diluted hydrochloric acid, the solution was extracted with diethyl ether (2 × 100 mL) and the combined organic phases were dried (sodium sulfate). The solvent was removed in vacuo and the product was dried in high vacuum.

O OH

N N N N

C16H20N4O2 MW: 300.36 g/mol

Yield: 2.96 g (9.87 mmol, 68 %)

1 ◦ 5 3 H NMR (300 MHz, CDCl3, 25 C): δ = 2.28 (s, 6 H, C -CH3), 2.32 (s, 6 H, C -CH3), 2 3 2 5.24 (dd, J H,H = 0.8 Hz, J H,H = 11.6 Hz, 2 H, (Z)-H2C=), 5.34 (dd, J H,H = 0.8 Hz, 3 3 3 J H,H = 17.9 Hz, 2 H, (E)-H2C=), 6.45 (dd, J H,H = 17.9 Hz, J H,H = 11.7 Hz, 2 H,

-HC=), 6.83 (s, 1 H, CbridgeH) ppm.

13 ◦ 5 3 C NMR (75.5 MHz, CDCl3, 25 C): δ = 10.0 (C -CH3), 13.4 (C -CH3), 70.5 (Cbridge), 4 5 3 − 114.8 (H2C=), 115.7 (C ), 128.5 (-HC=), 137.3 (C ), 145.1 (C ), 165.4 (CO2 ) ppm.

167 6 Experimental Section

6.2.5 Synthesis of [MoO2Cl(bdmvpza)] (5) A solution of Hbdmvpza (4) (100 mg, 0.333 mmol) in tetrahydrofuran was charged with potassium tert-butoxide (0.0374 mg, 0.333 mmol). To the resulting mixture, molybdenum(VI) dichloride dioxide (66.0 mg, 0.333 mmol) was added. Subsequently, the reaction was stirred over night and ﬁltrated afterwards. All volatiles were removed and the remaining residue was dissolved in dichloromethane. The desired product was obtained by precipitation from this solution with diethyl ether and subsequent collection via ﬁltration. It was washed thoroughly with diethyl ether and dried in vacuum.

N N O O N N Mo Cl O O 5

C16H19ClMoN4O4 MW: 462.76 g/mol

Yield: 76.8 mg (0.166 mmol, 50 %)

1 ◦ 5 H NMR (symmetric cis-isomer, 300 MHz, DMSO-d6, 25 C): δ = 2.17 (s, 6 H, C - 3 2 3 CH3), 2.26 (s, 6 H, C -CH3), 5.12 (dd, J H,H = 1.0 Hz, J H,H = 11.5 Hz, 2 H, (Z)-H2C=), 2 3 3 5.28 (dd, J H,H = 1.0 Hz, J H,H = 18.0 Hz, 2 H, (E-H2C=), 6.51 (dd, J H,H = 17.9 Hz, 3 J H,H = 11.7 Hz, 2 H, -HC=), 7.27 (s, 1 H, -CbridgeH-) ppm.

1 ◦ H NMR (asymmetric trans-isomer, 300 MHz, DMSO-d6, 25 C): δ = 2.54 (s, 3 H, 5 5 5 5 3 3 C -CH3 or C ’-CH3), 2.61 (s, 3 H, C -CH3 or C ’-CH3), 2.71 (s, 3 H, C -CH3 or C ’-CH3), 3 3 2.79 (s, 3 H, C -CH3or C ’-CH3), 5.41 (m, AMX system, coupling not resolved, 4 H,

H2C=), 6.57 (m, AMX system, coupling not resolved, 2 H, -HC=), 7.05 (s, 1 H, CbridgeH) ppm.

13 ◦ 5 3 C NMR (75.5 MHz, DMSO-d6, 25 C): δ = 9.91 (C -CH3), 13.5 (C -CH3), 71.3 4 5 3 − (Cbridge), 112.7 (=CH2), 115.7 (C ), 127.4 (-HC=), 138.4 (C ), 145.6 (C ), 165.9 (CO2 ) ppm.

Elemental analysis of C16H19ClMoN4O4 (462.76 g/mol): calcd. C 41.53, H 4.14, N 12.11; found C 41.87, H 4.17, N 10.59 %.

−1 IR (KBr): νe = 942 (s, νsym(Mo=O)), 911 (s, νasym(Mo=O)) cm .

168 6.2 Oxo-Transfer Catalysis by Chelate and Scorpionate Oxomolybdenum Complexes

6.2.6 Copolymerization of bdmvpzm (2) with MMA to form P6

A solution of bdmvpzm (2) (85.0 mg, 0.332 mmol) in dry xylenes (10 mL) was charged with methyl methacrylate (MMA) (1.10 mL, 11.9 mmol). The resulting mixture was heated to a temperature of 80 ◦C. Azobisisobutyronitrile (AIBN) (20.0 mg, 0.120 mmol) was added to start the copolymerization. The reaction was stirred for ﬁve hours and subsequently poured in a mixture of methanol (300 mL) and diluted hydrochloric acid (3.00 mL). The resulting white precipitate was collected by ﬁltration and washed thoroughly with dry methanol and dried in vacuo.

N N MMA MMA N N

Yield: 0.310 g (28 %)

Elemental analysis: C 61.34, H 8.02, N 2.34 %.

Incorporation: 0.443 mmol/g.

169 6 Experimental Section

6.2.7 Copolymerization of bdmvpzm (2) with EGDMA to form P7

A solution of bdmvpzm (2) (85.0 mg, 0.332 mmol) in dry xylenes (10 mL) was charged with ethylene glycol dimethacrylate (EGDMA) (1.10 mL, 5.85 mmol). The resulting mixture was heated to a temperature of 80 ◦C. Azobisisobutyronitrile (AIBN) (20.0 mg, 0.120 mmol) were added to start the copolymerization. The reaction was stirred for ﬁve hours. Subsequently, the resulting white precipitate was collected by ﬁltration and washed thoroughly with dry methanol and dried in vacuo.

N N EGDMA EGDMA N N

Yield: 1.19 g (96 %)

Elemental analysis: C 60.83, H 7.15, N 1.74 %.

Incorporation: 0.310 mmol/g.

170 6.2 Oxo-Transfer Catalysis by Chelate and Scorpionate Oxomolybdenum Complexes

6.2.8 Copolymerization of Hbdmvpza (4) with MMA to form P8

A solution of Hbdmvpza (4) (100 mg, 0.333 mmol) in dry xylenes (10 mL) was charged with methyl methacrylate (MMA) (1.10 mL, 11.9 mmol). The resulting mixture was heated to a temperature of 80 ◦C. Azobisisobutyronitrile (AIBN) (20.0 mg, 0.120 mmol) was added to start the copolymerization. The reaction was stirred for ﬁve hours and subsequently poured in a mixture of methanol (300 mL) and diluted hydrochloric acid (3.00 mL). The resulting white precipitate was collected by ﬁltration and washed thoroughly with dry methanol and was dried in vacuo.

O OH

N N MMA MMA N N

Yield: 0.205 g (18 %)

Elemental analysis: C 60.31, H 7.58, N 3.51 %.

Incorporation: 0.624 mmol/g.

171 6 Experimental Section

6.2.9 Copolymerization of Hbdmvpza (4) with EGDMA to form P9

A solution of Hbdmvpza (4) (100.0 mg, 0.333 mmol) in dry xylene (10 mL) was charged with ethylene glycol dimethacrylate (EGDMA) (1.10 mL, 5.85 mmol). The resulting mixture was heated to a temperature of 80 ◦C. Azobisisobutyronitrile (AIBN) (20.0 mg, 0.120 mmol) was added to start the copolymerization. The reaction was stirred for ﬁve hours. Subsequently, the resulting white precipitate was collected by ﬁltration and washed thoroughly with dry methanol and was dried in vacuo.

O OH

N N EGDMA EGDMA N N

Yield: 1.21 g (97 %)

Elemental analysis: C 58.65, H 6.79, N 1.67 %.

Incorporation: 0.228 mmol/g.

172 6.2 Oxo-Transfer Catalysis by Chelate and Scorpionate Oxomolybdenum Complexes

6.2.10 Synthesis of P6-Mo

A suspension of P6 (0.300 mg, ligand content 0.441 mmol/g, equals 0.132 mmol) in tetrahydrofuran was treated with molybdenum(VI) dichloride dioxide (26.4 mg, 0.132 mmol). The resulting mixture was stirred for 24 hours at a temperature of 50 ◦C. Subsequently, all volatiles were removed and the residue was washed thoroughly with dry methanol. Afterwards, the polymer was dried in vacuo.

N N MMA Cl MMA N N Mo Cl O O

P6-Mo

AAS: Mo content = 0.271 mmol/g.

173 6 Experimental Section

6.2.11 Synthesis of P7-Mo

A suspension of P7 (0.300 mg, ligand content 0.310 mmol/g, equals 0.0930 mmol) in tetrahydrofuran was treated with molybdenum(VI) dichloride dioxide (18.6 mg, 0.0930 mmol). The resulting mixture was stirred for 24 hours at a temperature of 50 ◦C. Subsequently, all volatiles were removed and the residue was washed thoroughly with dry methanol. Afterwards, the polymer was dried in vacuo.

N N EGDMA Cl EGDMA N N Mo Cl O O

P7-Mo

AAS: Mo content = 0.0459 mmol/g.

174 6.2 Oxo-Transfer Catalysis by Chelate and Scorpionate Oxomolybdenum Complexes

6.2.12 Synthesis of P8-Mo

The copolymer P8 (500 mg, ligand content 0.624 g/mol, equals 0.312 mmol) was suspended in dry tetrahydrofuran. Potassium tert-butoxide (35.0 mg, 0.312 mmol) was added and the resulting mixture was stirred for one hour at a temperature of 50 ◦C. Subsequently, molybdenum(VI) dichloride dioxide (62.0 mg, 0.312 mmol) was added to the suspension. After 24 hours of stirring, the polymer was collected by ﬁltration, washed thoroughly with methanol and dried in vacuo.

N N MMA O O MMA N N Mo Cl O O

P8-Mo

AAS: Mo content = 0.490 mmol/g.

175 6 Experimental Section

6.2.13 Synthesis of P9-Mo

The copolymer P9 (500 mg, ligand content 0.228 g/mol, equals 0.114 mmol) was suspended in dry tetrahydrofuran. Potassium tert-butoxide (12.8 mg, 0.114 mmol) was added and the resulting mixture was stirred for one hour at a temperature of 50 ◦C. Subsequently, molybdenum(VI) dichloride dioxide (22.7 mg, 0.114 mmol) was added to the suspension. After 24 hours of stirring, the polymer was collected by ﬁltration, washed thoroughly with methanol and dried in vacuo.

N N EGDMA O O EGDMA N N Mo Cl O O

P9-Mo

AAS: Mo content = 0.0192 mmol/g.

176 6.2 Oxo-Transfer Catalysis by Chelate and Scorpionate Oxomolybdenum Complexes

6.2.14 Copolymerization of [MoO2Cl2(bdmvpzm)] (3) with MMA to form P10

A solution of [MoO2Cl2(bdmvpzm)] (3) (0.100 g, 0.220 mmol) in a mixture of acetonitrile (6.00 mL) and xylenes (2.00 mL) was treated with MMA (1.00 mL, 9.39 mmol). The resulting solution was heated to a temperature of 65 ◦C and AIBN (15.0 mg, 0.0913 mmol) was added. Subsequently, the solution was stirred for 24 hours. All volatiles were removed in vacuo and the residue was washed with dry methanol. The obtained material was dried in vacuum.

N N MMA Cl MMA N N Mo Cl O O

P10

Yield: 311 mg (30 %)

AAS: Mo content = 0.646 mmol/g.

−1 IR (KBr): νe = 947 (s, νsym(Mo=O)), 915 (s, νasym(Mo=O)) cm .

177 6 Experimental Section

6.2.15 Copolymerization of [MoO2Cl2(bdmvpzm)] (3) with EGDMA to form P11

A solution of [MoO2Cl2(bdmvpzm)] (3) (0.100 g, 0.220 mmol) in a mixture of acetonitrile (6.00 mL) and xylene (2.00 mL) was treated with EGDMA (1.00 mL, 5.30 mmol). The resulting solution was heated to a temperature of 65 ◦C and AIBN (40.0 mg, 0.240 mmol) was added. Subsequently, the solution was stirred for 24 hours. All volatiles were removed in vacuo and the residue was washed with dry methanol. The obtained material was dried in vacuum.

N N EGDMA Cl EGDMA N N Mo Cl O O

P11

Yield: 539 mg (47 %)

AAS: Mo content = 0.0334 mmol/g.

−1 IR (KBr): νe = 944 (w, νsym(Mo=O)), 919 (w, νasym(Mo=O)) cm .

178 6.2 Oxo-Transfer Catalysis by Chelate and Scorpionate Oxomolybdenum Complexes

6.2.16 Copolymerization of [MoO2Cl(bdmvpza)] (5) with MMA to form P12

A solution of [MoO2Cl(bdmvpza)] (5) (0.100 g, 0.216 mmol) in a mixture of acetonitrile (6.00 mL) and xylenes (2.00 mL) was treated with MMA (1.00 mL, 9.39 mmol). The resulting solution was heated to a temperature of 65 ◦C and AIBN (15.0 mg, 0.0913 mmol) was added. Subsequently, the solution was stirred for 24 hours. All volatiles were removed in vacuo and the residue was washed with dry methanol. The obtained material was dried in vacuum.

N N MMA O O MMA N N Mo Cl O O

P12

Yield: 281.0 mg (27 %)

AAS: Mo content = 0.401 mmol g−1.

−1 IR (KBr): νe = 941 (s, νsym(Mo=O)), 911 (s, νasym(Mo=O)) cm .

179 6 Experimental Section

6.2.17 Copolymerization of [MoO2Cl(bdmvpza)] (5) with EGDMA to form P13

A solution of [MoO2Cl(bdmvpza)] (5) (0.100 g, 0.216 mmol) in a mixture of acetonitrile (6.00 mL) and xylenes (2.00 mL) was treated with EGDMA (1.00 mL, 5.30 mmol). The resulting solution was heated to a temperature of 65 ◦C and AIBN (15.0 mg, 0.0913 mmol) was added. Subsequently, the solution was stirred for 24 hours. All volatiles were removed in vacuo and the residue was washed with dry methanol. The obtained material was dried in vacuum.

N N EGDMA O O EGDMA N N Mo Cl O O

P13

Yield: 516 mg (45 %)

AAS: Mo content = 0.0307 mmol g−1.

−1 IR (KBr): νe = 943 (s, νsym(Mo=O)), 911 (s, νasym(Mo=O)) cm .

180 6.3 4-Ethynyl Substituted Bis(pyrazolyl)methane Ligands

6.3 4-Ethynyl Substituted Bis(pyrazolyl)methane Ligands

6.3.1 Synthesis of Bis(4-(2,2-dibromovinyl)-3,5-dimethylpyrazol-1- yl)methane (14)

Tertrabromomethane (5.08 g, 15.32 mmol) was dissolved in dichloromethane at a temperature of 0 ◦C. Triphenylphosphine (8.04 g, 30.6 mmol) was slowly added. Subse- quently, bis(3,5-dimethyl-4-formylpyrazol-1-yl)methane (1.00 g, 3.83 mmol) and triethylamine (5.00 mL, 35.8 mmol) were given to the reaction mixture. The cooling was removed and the solution was stirred for 72 h. After that time, the solvent was removed in vacuo and the residue was puriﬁed via column chromatography (silica, n-pentane:ethyl acetate 7:3 v/v).

Br Br Br Br N N N N H H

C15H16Br4N4 MW: 571.94 g/mol

Yield: 1.84 g (3.22 mmol, 84.1 %)

1 ◦ 3 5 H NMR (300 MHz, CDCl3, 25 C): δ = 2.11 (s, 6 H, C -CH3), 2.38 (s, 6 H, C -CH3),

6.01 (s, 2 H, -CH2-), 7.18 (s, 2 H, Br2C=C-H) ppm.

13 ◦ 3 5 C NMR (75.5 MHz, CDCl3, 25 C): δ = 11.6 (C -CH3), 13.2 (C -CH3), 54.0 (-CH2-), 4 5 3 61.0 (C-Br2), 93.0 (H-C=), 116.1 (C ), 138.8 (C ), 147.3 (C ) ppm.

Elemental analysis of C15H16Br4N4 (571.93 g/mol): calcd. C 31.50, H 2.82, N 9.80; found C 31.35, H 2.58, N 9.95 %.

181 6 Experimental Section

6.3.2 Synthesis of Bis(4-ethynyl-3,5-dimethylpyrazol-1-yl)methane (bedmpzm) (15)

A solution of bis(4-(2,2-dibromovinyl)-3,5-dimethylpyrazol-1-yl)methane (14) (0.300 g, 0.525 mmol) in diethyl ether (50 mL) was cooled to 0 ◦C. N -butyllithium (2.30 ml, 3.68 mmol, 1.60 m in n-hexane) was added slowly and the resulting yellow solution was stirred for 20 minutes. The reaction was quenched by addition of a satured solution of ammonium chloride (10 mL). The solution was stirred for additional 30 minutes until it was extracted with diethyl ether (3 × 20 mL). The combined organic phases were dried over sodium sulfate and the solvent was removed in vacuo. The remaining residue was washed with methanol to remove impurities.

N N N N

C15H16N4 MW: 252.32 g/mol

Yield: 92.0 mg (0.365 mmol, 69.5 %)

1 ◦ 3 5 H NMR (300 MHz, DMSO-d6, 25 C): δ = 2.10 (s, 6 H, C -CH3), 2.44 (s, 6 H, C -CH3),

4.15 (s, 2 H, C≡C-H), 6.13 (s, 2 H, -CH2-) ppm.

13 ◦ 3 5 C NMR (75.5 MHz, DMSO-d6, 25 C): δ = 10.5 (C -CH3), 12.3 (C -CH3), 60.7 (- 4 5 3 CH2-), 75.4 (C≡C), 81.1 (C≡C), 102.4 (C ), 144.2 (C ), 151.1 (C ) ppm.

Elemental analysis of C15H16N4 (252.32 g/mol): calcd. C 71.40, H 6.39, N 22.21; found C 70.97, H 6.02, N 22.50 %.

−1 IR (KBr): νe = 3221 (s, C≡C-H), 2106 (m, C≡C), 1555 (m, C=N) cm .

182 6.3 4-Ethynyl Substituted Bis(pyrazolyl)methane Ligands

6.3.3 Synthesis of [CuI(bedmpzm)] (17)

A solution of bis((4-ethynyl)-3,5-dimethylpyrazol-1-yl)methane (bedmpzm) (15) (0.150 g, 0.595 mmol) and copper iodide (0.113 g, 0.595 mmol) in acetonitrile (15 mL) was stirred for 30 minutes at room temperature. During this time, a white precipitate was formed, which was ﬁltered oﬀ and dried in vacuo.

N N N N Cu I 17

C15H16N4CuI MW: 442.77 g/mol

Yield: 0.224 g (0.505 mmol, 85 %)

1 ◦ 3 3 H NMR (300 MHz, DMSO-d6, 25 C): δ = 2.20 (s, 6 H, C -CH3), 2.45 (s, 6 H, C -CH3),

4.20 (s, 2 H, C≡C-H), 6.23 (s, 2 H, -CH2-) ppm.

A 13C NMR spectrum could not be collected due to low solubility.

Elemental analysis of C15H16N4CuI (442.77 g/mol): calcd. C 40.69, H 3.64, N 12.65; found C 40.76, H 3.49, N 12.43 %.

−1 IR (KBr): νe = 3302 (s, C≡C-H), 2112 (m, C≡C), 1555 (m, C=N) cm .

183 6 Experimental Section

6.3.4 Synthesis of [ZnCl2(bedmpzm)] (18) A solution of bis((4-ethynyl)-3,5-dimethylpyrazol-1-yl)methane (bedmpzm) (15) (0.150 g, 0.594 mmol) and zinc(II) chloride (0.0810 g, 0.594 mmol) in acetonitrile (15 mL) was stirred for one hour until the formation of a white precipitate occured, which was ﬁltered oﬀ and dried in vacuo.

N N N N Zn Cl Cl 18

C15H16N4ZnCl2 MW: 388.60 g/mol

1 ◦ 3 5 H NMR (300 MHz, DMSO-d6, 25 C): δ = 2.10 (s, 6 H, C -CH3), 2.44 (s, 6 H, C -CH3),

4.15 (s, 2 H, C≡C-H), 6.14 (s, 2 H, -CH2-) ppm.

A 13C NMR spectrum could not be collected due to low solubility.

Elemental analysis of C15H16N4ZnCl2 (388.60 g/mol): calcd. C 46.36, H 4.15, N 14.42; found C 46.27, H 4.00, N 14.15 %.

−1 IR (KBr): νe = 3244 (C≡C-H), 2110 (C≡C), 1549 (m, C=N) cm .

184 6.3 4-Ethynyl Substituted Bis(pyrazolyl)methane Ligands

6.3.5 Synthesis of [MnCl2(bedmpzm)] (19) A solution of bis((4-ethynyl)-3,5-dimethylpyrazolyl)methane (bedmpzm) (15) (0.150 g, 0.594 mmol) and manganese(II) chloride (0.0750 g, 0.594 mmol) in acetonitrile (15 mL) was stirred for one hour at room temperature. The formed precipitate was ﬁltered oﬀ, washed with diethyl ether (3 × 5 mL) and dried in vacuo.

N N N N

Cl Mn Cl

N N N N

C30H32N8MnCl2 MW: 630.48 g/mol

Yield: 0.154 g (0.244 mmol, 82 %)

Elemental analysis of C30H32N8MnCl2 (630.48 g/mol): calcd. C 57.15, H 5.12, N 17.77; found C 57.26, H 4.88, N 17.49.

−1 IR (KBr): νe = 3257 (s, C≡C-H), 2105 (m, C≡C), 1556 (m, C=N) cm .

185 6 Experimental Section

6.3.6 Synthesis of [CoCl2(bedmpzm)] (20) A solution of bis((4-ethynyl)-3,5-dimethylpyrazolyl)methane (bedmpzm) (15) (0.150 g, 0.594 mmol) and cobalt(II) chloride (0.141 g, 0.594 mmol) in acetonitrile (15 mL) was stirred over night. The resulting deep blue precipitate was ﬁltered oﬀ and dried in vacuo.

N N N N Co Cl Cl 20

C15H16N4CoCl2 MW: 382.15 g/mol

Yield: 0.182 g (0.475 mmol, 80 %)

Elemental analysis of C15H16N4CoCl2 (382.15 g/mol): calcd. C 47.14, H 4.22, N 14.66; found C 47.29, H 4.33, N 14.65 %.

−1 IR (KBr): νe = 3265 (s, C≡C-H), 2114 (w, C≡C), 1551 (m, C=N) cm .

186 6.3 4-Ethynyl Substituted Bis(pyrazolyl)methane Ligands

6.3.7 Synthesis of [MoO2Cl2(bedmpzm)] (21) A solution of molybdenum(VI) dichloride dioxide (0.317 g, 1.60 mmol) in tetrahydrofuran was treated with bis((4-ethynyl)-3,5-dimethylpyrazolyl)methane (bedmpzm) (15) (0.402 g, 1.60 mmol). After stirring for one hour, the resulting precipiate was ﬁltered oﬀ and dried in vacuo.

N N N N Mo Cl Cl O O 21

C15H16N4O2MoCl2 MW: 451.81 g/mol

Yield: 470 mg (1.23 mmol, 77 %)

1 ◦ 3 5 H NMR (300 MHz, DMSO-d6, 25 C): δ = 2.10 (s, 6 H, C -CH3), 2.44 (s, 6 H, C -CH3),

4.15 (s, 2 H, C≡C-H), 6.14 (s, 2 H, -CH2-) ppm.

13 ◦ 3 5 C NMR (75.5 MHz, DMSO-d6, 25 C): δ = 10.1 (C -CH3), 12.1 (C -CH3), 59.5 (CH2), 75.4 (C≡C), 84.1 (C≡C), 101.2 (C4), 143.9 (C3), 149.9 (C5) ppm.

Elemental analysis of C15H16N4O2MoCl2 (451.18 g/mol): calcd. C 39.93, H 3.75, N 12.42; found C 40.33, H 3.22, N 11.61 %.

IR (KBr): νe = 3274 (s, C≡C-H), 2118 (w, C≡C), 1557 (m, C=N), 948 (s, νsym(Mo=O)), −1 919 (vs, νasym(Mo=O)) cm .

187 6 Experimental Section

6.3.8 Synthesis of 4-Iodopyrazole (22)

To a solution of pyrazole (22.9 g, 336 mmol) and iodine (50.1 g, 201 mmol) in acetonitrile (250 mL) was slowly added cer(IV)ammoniumnitrate (92.0 g, 186 mmol). After three hours of stirring, the volatiles were removed and the remaining residue was dissolved in ethyl acetate (250 mL) and water (250 mL). A saturated solution of sodium thiosulfate was slowly added until the red color disappeared. The organic phase was separated and washed with brine (2 × 250 mL), dried over sodium sulfate and the solvent removed in vacuo.

NH I N 22

C3H3IN2 MW: 193.98 g/mol

Yield: 53.0 g (273 mmol, 81 %)

1 ◦ H NMR (300 MHz, CDCl3, 25 C): δ = 7.65 (s, 2 H, CH) ppm.

188 6.3 4-Ethynyl Substituted Bis(pyrazolyl)methane Ligands

6.3.9 Synthesis of 4-Iodo-3,5-dimethylpyrazole (23)

To a solution of 3,5-dimethylpyrazole (32.3 g, 336 mmol) and iodine (50.1 g, 201 mmol) in acetonitrile (250 mL) was slowly added cer(IV)ammoniumnitrate (92.0 g, 186 mmol). After three hours of stirring, the volatiles were removed and the remaining residue was dissolved in ethyl acetate (250 mL) and water (250 mL). A saturated solution of sodium thiosulfate was slowly added until the red color disappeared. The organic phase was separated and washed with brine (2 × 250 mL), dried over sodium sulfate and the solvent removed in vacuo.

NH I N

C5H7IN2 MW: 222.03 g/mol

Yield: 52.0 g (234 mmol, 69.6 %)

1 ◦ H NMR (300 MHz, CDCl3, 25 C): δ = 2.20 (s, 6 H, CH3) ppm.

189 6 Experimental Section

6.3.10 Synthesis of 4-Iodo-1-tritylpyrazol (24)[77]

Sodium hydride (5.52 g, 138 mmol, 60 % in petrol ether) was added slowly to a solution of 4-iodopyrazole (22) (19.4 g, 100 mmol) in dry THF. After the addition of trityl chloride (27.9 g, 100 mmol), the reaction was stirred for three days. Afterwards, all volatiles were removed and the colorless residue was washed with water (3 × 50 mL) and diethyl ether (3 × 50 mL).

N I N

C22H17IN2 MW: 436.30 g/mol

Yield: 45.0 g (96.6 mmol, 41.3 %)

1 ◦ H NMR (300 MHz, CDCl3, 25 C): δ = 7.15 (m, 6 H, Trt), 7.34 (m, 9 H, Trt), 7.43 (s, 1 H, C5-H), 7.69 (s, 1 H, C3-H) ppm.

13 ◦ 4 C NMR (75.5 MHz, CDCl3, 25 C): δ = 55.6 (C ), 79.3 (C-(C6H5)3), 127.8 (Trt), 127.9 (Trt), 130.1 (Trt), 136.4 (C5), 142.7 (Trt), 144.7 (C3) ppm.

190 6.3 4-Ethynyl Substituted Bis(pyrazolyl)methane Ligands

6.3.11 Synthesis of 4-Iodo-3,5-dimethyl-1-tritylpyrazole (25)[71]

Sodium hydride (13.1 g, 327 mmol, 60 % in petrol ether) was added slowly to a solution of 4-iodo-3,5-dimethylpyrazole (23) (51.7 g, 233 mmol) in dry THF. After the addition of trityl chloride (65.2 g, 233 mmol), the reaction was stirred for three days. Afterwards, all volatiles were removed and the colorless residue was washed with water (3 × 50 mL) and diethyl ether (3 × 50 mL).

N I N

C24H21IN2 MW: 464.34 g/mol

Yield: 37.1 g (85.0 mmol, 85 %)

1 ◦ H NMR (300 MHz, CDCl3, 25 C): δ = 1.58 (s, 3 H, CH3), 2.23 (s, 3 H, CH3), 7.10 (m, 6 H, Trt), 7.27 (m, 9 H, Trt) ppm.

13 ◦ 5 3 4 C NMR (75.5 MHz, CDCl3, 25 C): δ = 14.6 (C -CH3), 15.7 (C -CH3), 66.9 (C ), 5 3 78.9 (C-(C6H5)3), 127.3 (Trt), 127.5 (Trt), 130.3 (Trt), 142.5 (C ), 142.9 (Trt), 147.5 (C ) ppm.

191 6 Experimental Section

6.3.12 Synthesis of 3,5-Dimethyl-4-(trimethylsilyl)ethynyl-1-tritylpyrazole (26)

A solution of 4-iodo-3,5-dimethyl-1-tritylpyrazole (25) (15.0 g, 32.0 mmol) in dimethylformamide (150 mL) was treated with copper(I) iodide (1.22 g, 6.40 mmol), bis(triphenylphosphine)palladium dichloride (2.27 g, 3.23 mmol), triethyl amine (22.2 mL, 160 mmol) and trimethylsilylacetylene (4.88 mL, 35.2 mmol). The solution was stirred for 24 hours at a temperature of 60 ◦C. Subsequently, volatiles were removed under vacuo and the remaining residue was dissolved in dichloromethane and water (2:1 v/v, 300 mL). Af- ter the phases were separated, the aqueous phase was extracted with dichloromethane (3 × 75 mL) and the combined organic phases were dried (sodium sulfate). The solvent was removed and the crude product was puriﬁed via column chromatography (silica, n-hexane:ethyl acetate 7:3 v/v).

N Si N

C29H30N2Si MW: 434.66 g/mol

Yield: 9.93 g (22.8 mmol, 71.3 %)

1 ◦ 5 H NMR (300 MHz, CDCl3, 25 C): δ = 0.23 (s, 9 H, Si(CH3)3), 1.57 (s, 3 H, C -CH 3), 3 2.26 (s, 3 H, C -CH 3), 6.85-6.95 (m, 6 H, Trt), 7.00-7.10 (m, 9 H, Trt) ppm.

13 ◦ 5 3 C NMR (75.5 MHz, CDCl3, 25 C): δ = 0.23 (Si(CH3)3), 12.9 (C -CH3), 13.9 (C - 4 CH3), 78.6 (C-(C6H5)3), 97.9 (C≡C), 98.1 (C≡C), 104.4 (C ), 127.3 (Trt), 127.5 (Trt), 130.3 (Trt), 142.8 (Trt), 145.4 (C5), 148.1 (C3) ppm.

Elemental analysis of C29H30N2Si (434.66 g/mol): calcd. C 80.14, N 6.45, H 6.96; found C 79.55, N 6.27, H 6.93 %.

+ + + ESI MS: m/z (%) = 243.11 (46) [Trt] , 457.21 (80) [M+Na] , 891.42 (100) [M2+Na] .

−1 IR (KBr): νe = 2152 (s, C≡C), 1551 (m, C=N) 1250 (s, Si-CH3), 861 (vs, Si-CH3) cm .

192 6.3 4-Ethynyl Substituted Bis(pyrazolyl)methane Ligands

6.3.13 Synthesis of 4-(Trimethylsilyl)ethynyl-1-tritylpyrazole (27)

A solution of 4-iodo-1-tritylpyrazole (24) (5.00 g, 11.5 mmol) in dimethylformamide (75 mL) was treated with copper(I) iodide (0.436 g, 2.29 mmol), bis(triphenylphosphine)- palladium dichloride (0.807 g, 1.15 mmol), triethyl amine (8.00 mL, 57.3 mmol) and trimethylsilylacetylene (1.75 mL, 12.6 mmol). The solution was stirred for 24 hours at a temperature of 60 ◦C. Subsequently, volatiles were removed under vacuo and the remaining residue was dissolved in dichloromethane and water (2:1 v/v, 350 mL). After the phases were separated, the aqueous phase was extracted with dichloromethane (3 × 50 mL) and the combined organic phases were dried (sodium sulfate). The solvent was removed and the crude product was puriﬁed via column chromatography (silica, n-hexane:ethyl acetate 9:1 v/v).

N Si N

C27H26N2Si MW: 406.60 g/mol

Yield: 3.18 g (7.82 mmol, 68 %)

1 ◦ H NMR (300 MHz, CDCl3, 25 C): δ = 0.21 (s, 9 H, Si(CH3)3), 7.13 (m, 6 H, Trt), 7.29 (m, 9 H, Trt), 7.56 (s, 1 H, C3-H), 7.77 (s, 1 H, C5-H) ppm.

13 ◦ C NMR (75.5 MHz, CDCl3, 25 C): δ = −0.06 (Si(CH3)3), 79.0 (C-(C6H5)3), 95.1 (C≡C), 96.5 (C≡C), 101.9 (C4), 127.7 (Trt), 127.8 (Trt), 130.0 (Trt), 135.6 (Trt), 142.5 (C5), 142.5 (C3) ppm.

Elemental analysis of C27H26N2Si (406.60 g/mol): calcd. C 79.76, H 6.89, N 6.45; found C 79.84, H 6.39, N 6.90 %.

+ + + ESI MS: m/z (%) = 243.12 (60) [Trt] , 333.14 (18) [M−Si(CH3)3] , 429.18 (82) [M+Na] , + + 739.32 [M+(M−Si(CH3)3)] , 835.36 (100) [2M+Na] .

−1 IR (KBr): νe = 2164 (s, C≡C), 1545 (w, C=N), 1248 (m, Si-CH3), 864 (s, Si-CH3) cm .

193 6 Experimental Section

6.3.14 Synthesis of 3,5-Dimethyl-4-(trimethylsilyl)ethynylpyrazole (28)

A solution of 3,5-dimethyl-4-(trimethylsily)ethynyl-1-tritylpyrazole (26) (9.93 g, 22.8 mmol) in dichloromethane (300 mL) and water (6 mL) was treated with triﬂuoroacetic acid (3.87 mL, 50.6 mmol). The reaction was stirred for 24 hours at room temperature. Subsequently, the solution was neutralized with a saturated solution of sodium carbonate. The organic phase was washed with water (2 × 40 mL) and dried (sodium sulfate). All volatiles were removed and the residue was puriﬁed via column chromatography (silica, chloroform to remove impurities, then chloroform:acetone 9:1 v/v).

Yield: 1.78 g (9.25 mmol, 41 %)

Alternative Synthesis: A solution of 4-iodopyrazole (23) (5.00 g, 22.5 mmol) in dimethylformamide (70 mL) was treated with bis(triphenylphosphine)palladium dichloride (1.58 g, 0.0275 mmol), cooper(I) iodide (0.857 g, 4.50 mmol), triethyl amine (15.6 mL, 113 mmol) and trimethylsilylacetylene (4.68 mL, 33.8 mmol). The resulting mixture was stirred for 24 hours at a temperature of 60 ◦C. After this time, all volatiles were distilled oﬀ and the residue was puriﬁed via column chromatography (silica, n-hexane:ethyl acetate 6:4 v/v).

NH Si N

C10H16N2Si MW: 192.34 g/mol

Yield: 3.41 g (17.7 mmol, 79 %)

1 ◦ H NMR (300 MHz, CDCl3, 25 C): δ = 0.24 (s, 9 H, Si(CH3)3), 2.31 (s, 6 H, CH3), 10.45 (s, 1 H, NH) ppm.

13 ◦ 3 5 C NMR (75.5 MHz, CDCl3, 25 C): δ = 0.21 (Si(CH3)3), 11.3 (C - and C -CH3), 97.0 (C≡C), 97.7 (C≡C), 101.5 (C4), 147.2 (C3 and C5) ppm.

Elemental analysis of C10H16N2Si (192.34 g/mol): calcd. 62.45, N 14.57, H 8.38; found 62.55, N 14.20, H 8.24 %.

ESI MS: m/z (%) = 193.11 (100) [MH]+.

194 6.3 4-Ethynyl Substituted Bis(pyrazolyl)methane Ligands

−1 IR (KBr): νe = 2155 (vs, C≡C), 1557 (w, C=N), 1250 (s, Si-CH3), 867 (vs, Si-CH3) cm .

6.3.15 Synthesis of 2,2-Bis(4-ethynyl-3,5-dimethylpyrazol-1- yl)acetic acid (29)

3,5-Dimethyl-4-(trimethylsilyl)ethynyl-1-tritylpyrazole (26) (1.78 g, 9.25 mmol) was dissolved in tetrahydrofuran (300 mL). Potassium hydroxide (1.55 g, 27.6 mmol), potassium carbonate (3.81 g, 27.6 mmol), benzyltriethylammonium chloride (0.210 g, 0.922 mmol) and dibromoacetic acid (1.01 g, 4.64 mmol) were added to the solution. The resulting reaction mixture was heated to reﬂux at 75 ◦C and stirred for three days. Subsequently, all volatiles were removed in vacuo. The remaining residue was dissolved in water (50 mL) and the pH value of the solution was adjusted to a value of 3. It was extracted with diethyl ether (3 × 50 mL), the combined organic phases were dried (sodium sulfate) and the solvent was removed in vacuo.

HO O

N N N N

C16H16N4O2 MW: 296.33 g/mol

Yield: 0.590 g (1.99 mmol, 43.0 %)

1 ◦ 5 3 H NMR (300 MHz, CDCl3, 25 C): δ = 2.23 (s, 6 H, C -CH 3), 2.35 (s, 6 H, C -CH 3),

3.19 (s, 2 H, C≡CH ), 6.82 (s, 1 H, CbridgeH), 9.86 (s, 1 H, CO2H) ppm.

13 ◦ 5 3 C NMR (75.5 MHz, CDCl3, 25 C): δ = 10.6 (C -CH3), 12.4 (C -CH3), 81.6 (Cbridge), 4 5 3 103.3 (C≡C), 124.8 (C≡C), 144.7 (C ), 146.7 (C ), 151.4 (C ), 166.0 (CO2H) ppm.

+ + ESI MS: m/z (%) = 333.1 (60) [M+K] , 172.1 (90) [C7H7N2+K] .

−1 IR (KBr): νe = 3288 (vs, C≡C-H), 2122 (m, C≡C), 1748 (vs, CO2H), 1562 (s, C=N) cm .

195 6 Experimental Section

6.3.16 Synthesis of (2-Hydroxyphenyl)-bis(3,5-dimethyl-4-(trimethylsilyl)ethynylpyrazol-1-yl)methane [HOPhbdmeTMSpzm] (30)

Sodium hydride (0.370 g, 9.24 mmol, 60 % in petrol ether) was suspended in dry tetrahydrofuran (40 mL) at a temperature of 0 ◦C. The mixture was treated with 3,5-dimethyl- 4-(trimethylsilyl)ethynylpyrazole (28) (1.71 g, 8.91 mmol) and allowed to stir at this temperature for 30 minutes. After this time, thionyl chloride (0.346 mL, 4.75 mmol) was added slowly and the solution was stirred for additional 30 minutes. Then the cooling was removed and the mixture was treated with salicylaldehyde (1.13 g, 9.24 mmol) and pyridine (0.747 mL, 9.24 mmol). The resulting solution was heated to reflux for 16 hours. Subsequently, excess aldehyde and pyridine were distilled off in a vacuum distillation at 105 ◦C. The remaining residue was redissolved in dichloromethane and washed with water (3 × 50 mL). The organic phase was dried (sodium sulfate) and the volatiles were removed in vacuo. The crude product was purified via column chromatography (silica, n-hexane:ethyl acetate 8:2 v/v) to obtain 30 as a colorless solid.

N N Si Si N N

C27H36N4OSi2 MW: 488.78 g/mol

Yield: 0.408 g (0.835 mmol, 19 %)

1 ◦ 3 H NMR (300 MHz, CDCl3, 25 C): δ = 0.23 (s, 18 H, Si(CH3)3), 2.14 (s, 6 H, C -CH3), 5 3 2.23 (s, 6 H, C -CH3), 6.79 (m, 3 H, CAr-H), 7.15 (t, 1 H, J H,H = 7.21 Hz, CAr-H), 7.40

(s, 1 H, CbridgeH), 9.03 (s, 1 H, OH) ppm.

13 ◦ 5 3 C NMR (75.5 MHz, CDCl3, 25 C): δ = 0.15 (Si(CH3)3), 10.6 (C -CH3), 12.6 (C - 4 CH3), 72.9 (Cbridge), 96.4 (C≡C), 98.8 (C≡C), 104.0 (C ), 117.8 (Car), 120.0 (Car), 121.1 5 3 (Car), 129.2 (Car), 131.0 (Car), 143.7 (C ), 150.8 (C ), 154.8 (Car-OH) ppm.

Elemental analysis of C27H36N4OSi2 (488.78 g/mol): calcd. C 66.35, N 11.46, H 7.42; found C 66.37, N 11.08, H 7.64 %.

ESI MS: m/z (%) = 511.23 (100) [M+Na]+, 999.47 (90) [2M+Na]+.

196 6.3 4-Ethynyl Substituted Bis(pyrazolyl)methane Ligands

IR (KBr): νe = 3143 (br, OH), 2156 (s, C≡C), 1559 (m, C=N), 1249 (s, Si-CH3), 859 (vs, −1 Si-CH3) cm .

TMS 6.3.17 Synthesis of [MoO2Cl2(HOPhbdme pzm)] (31)

Molybdenum(VI) dichloride dioxide (29.2 mg, 0.147 mmol) was dissolved in tetrahydrofuran (10 mL). The resulting solution was stirred for ten minutes at room temperature. Subsequently, [HOPhbdmeTMSpzm] (30) (70.0 mg, 0.147 mmol) was added. The reaction mixture turned yellow. After one hour, the solution was filtered and the filtrate was treated with n-hexane (15 mL). The desired complex precipitated after ten minutes while stirring and was collected by filtration.

N N Si Cl Si N N Mo O O Cl 31

C27H36Cl2MoN4O3Si2 MW: 687.64 g/mol

Yield: 27.3 mg (0.0397 mmol, 27 %)

1 ◦ 3 H NMR (300 MHz, CDCl3, 25 C): δ = 0.23 (s, 18 H, Si(CH3)3), 2.55 (s, 6 H, C -CH 3), 5 3 3 2.75 (s, 6 H, C -CH 3), 6.85 (t, J H,H = 7.5 Hz, 1 H, Car-H), 6.93 (t, J H,H = 4.5 Hz, 1 H, 3 3 Car-H), 7.09 (d, J H,H = 9.0 Hz, 1 H, Car-H), 7.30 (s, 1 H, CbridgeH), 7.33 (d, J H,H =

6.0 Hz, 1 H, CAr-H) ppm.

13 ◦ 3 5 C NMR (75.5 MHz, CDCl3, 25 C): δ = −0.05 (Si(CH3)3), 11.0 (C -CH3), 13.9 (C - 4 CH3), 70.4 (Cbridge), 93.8 (C≡C), 100.9 (C≡C), 106.3 (C ), 120.6 (Car), 120.7 (Car), 121.8 3 5 (Car), 128.4 (Car), 132.6 (Car), 142.8 (C ), 156.7 (C ), 157.1 (Car-OH) ppm.

Elemental analysis of C27H36Cl2MoN4O3Si2 (687.64 g/mol): calcd. C 47.16, H 5.28, N 8.15; found C 46.11, H 5.27, N 7.41 %.

IR (KBr): νe = 3440 (br, OH), 2160 (s, C≡C), 1559 (w, C=N), 1249 (s, Si-CH3), 941 (m, −1 νsym(Mo=O)), 921 (vs, νasym(Mo=O)), 866 (vs, Si-CH3) cm .

197 6 Experimental Section

6.3.18 Synthesis of (2-Hydroxyphenyl)-bis(3,5-dimethyl-4-ethynylpyrazol-1-yl)methane (32)

Procedure (i) [HOPhbdmeTMSpzm] (30) (100 mg, 0.210 mmol) was dissolved in a mixture of tetrahydrofuran (5 mL) and methanol (10 mL). The resulting solution was treated with potassium ﬂuoride (244 mg, 4.20 mmol) and stirred for six hours at room temperature. Afterwards, all volatiles were removed in vacuo and the residue was suspended in a saturated solution of sodium carbonate (10 mL). The aqueous suspension was extracted with diethyl ether (3 × 30 mL) and the combined organic phases were dried (sodium sulfate). The solvent was removed and the product was obtained as a white solid.

Yield: 56.4 mg (0.164 mmol, 78 %)

N N N N

C21H20N4O MW: 344.42 g/mol

Procedure (ii) [HOPhbdmeTMSpzm] (30) (50.0 mg, 0.105 mmol) was dissolved in a mixture of tetrahydrofuran (5 mL) and methanol (10 mL). The resulting solution was treated with potassium carbonate (145 mg, 1.05 mmol) and stirred over night at room temperature. After this time, all volatiles were removed in vacuo and the residue was redissolved in dichloromethane (30 mL) and the resulting solution was washed with water (3 × 30 mL). Subsequently, the organic phase was dried over sodium sulfate and the solvent was removed.

Yield: 27.4 mg (0.0796 mmol, 76 %)

1 ◦ 3 5 H NMR (300 MHz, CDCl3, 25 C): δ = 2.18 (s, 6 H, C -CH 3), 2.23 (s, 6 H, C -CH 3), 3 3.20 (s, 2 H, C≡C-H), 6.81 (m, 3 H, Car-H), 7.15 (t, 1 H, J H,H = 6.0 Hz, Car-H), 7.45 (s,

1 H, Cbridge) ppm.

13 ◦ 3 5 C NMR (75.5 MHz, CDCl3, 25 C): δ = 10.5 (C -CH3), 12.5 (C -CH3), 75.3 (C≡C), 4 81.4 (C≡C), 102.7 (C ), 119.8 (Car), 119.9 (Car), 121.0 (Car), 125.5 (Car), 130.9 (Car),

198 6.3 4-Ethynyl Substituted Bis(pyrazolyl)methane Ligands

3 5 144.1 (C ), 150.9 (C ), 154.8 (Car-OH) ppm. Cbridge could not be resolved.

ESI MS: m/z (%) = 367.15 (100) [M+Na]+, 711.32 (26) [2M+Na]+.

−1 IR (KBr): νe = 3430 (br, OH), 3291 (vs, C≡C-H), 2114 (m, C≡C), 1559 (m, C=N) cm .

6.3.19 Synthesis of (1-Methylimidazol-2-yl)-bis(3,5-dimethyl-4- (trimethylsilyl)ethynylpyrazol-1-yl)methane (33)

Sodium hydride (0.370 g, 9.24 mmol, 60 % in petrol ether) was suspended in dry tetrahydrofuran (40 mL) at a temperature of 0 ◦C. The mixture was treated with 3,5-dimethyl- 4-(trimethylsilyl)ethynylpyrazole (28) (1.71 g, 8.91 mmol) and allowed to stir at this temperature for 30 minutes. After this time, thionyl chloride (0.346 mL, 4.75 mmol) was added slowly and the solution was stirred for additional 30 minutes. Then the cooling was removed and the mixture was treated with 1-methyl-2-imidazolecarboxaldehyde (1.02 g, 9.24 mmol) and pyridine (0.747 mL, 9.24 mmol). The resulting solution was heated to reflux for 16 hours. Subsequently, excess aldehyde and pyridine were distilled off in a vacuum distillation at 105 ◦C. The remaining residue was redissolved in dichloromethane (50 mL) and washed with water (3 × 50 mL). The organic phase was dried (sodium sulfate) and the volatiles were removed in vacuo. The crude product was purified via column chromatography (silica, n-hexane:ethyl acetate 1:9 v/v) to obtain 33 as a brownish solid.

N N

N N Si Si N N

C25H36N6Si2 MW: 476.78 g/mol

Yield: 0.369 g (0.774 mmol, 17 %)

1 ◦ 3 H NMR (300 MHz, CDCl3, 25 C): δ = 0.22 (s, 18 H, Si(CH3)3), 2.17 (s, 6 H, C -CH3) 5 3 2.23 (s, 6 H, C -CH3), 3.33 (s, 3 H, CIm-CH3), 6.93 (d, 1 H, J H,H = 0.9 Hz), 7.05 (d, 1 3 H, J H,H = 1.0 Hz), 7.48 (s, 1 H, CbridgeH) ppm.

13 ◦ 5 3 C NMR (75.5 MHz, CDCl3, 25 C): δ = 0.14 (Si(CH3)3), 10.7 (C -CH3), 12.6 (C - 4 CH3), 33.0 (Nimid-CH3), 70.5 (Cbridge), 97.5 (C≡C), 95.5 (C≡C), 104.7 (C ), 123.0 (Cimid),

199 6 Experimental Section

5 3 128.2 (Cimid), 140.1 (C ), 144.4 (C ), 150.8 (Cimid) ppm.

Elemental analysis of C25H36N6Si2 (476.78 g/mol): calcd. C 62.98, N 17.63, H 7.61; found C 62.64, N 16.84, H 7.65 %.

ESI MS: m/z (%) = 975 (100) [2M+Na]+, 477 (100) [M+H]+.

−1 IR (KBr): νe = 2156 (s, C≡C), 1559 (w, C=N), 1250 (Si-CH3), 861 (vs, Si-CH3) cm .

6.3.20 Synthesis of (1-Methylimidazol-2-yl)-bis(3,5-dimethyl-4- ethynylpyrazol-1-yl)methane (34)

Procedure (i) (1-Methylimidazol-2-yl)-bis(3,5-dimethyl-4-(trimethylsilyl)ethynylpyrazol-1-yl)methane (33) (100 mg, 0.210 mmol) was dissolved in a mixture of tetrahydrofuran (5 mL) and methanol (10 mL). The resulting solution was treated with potassium ﬂuoride (244 mg, 4.20 mmol) and stirred for six hours at room temperature. Afterwards, all volatiles were removed in vacuo and the residue was suspended in a saturated solution of sodium carbonate (10 mL). The aqueous suspension was extracted with diethyl ether (3 × 30 mL) and the combined organic phases were dried (sodium sulfate). The solvent was removed and the product was obtained as a white solid.

Yield: 50.9 mg (0.153 mmol, 73 %)

N N

N N N N

C19H20N6 MW: 332.41 g/mol

Procedure (ii) (1-Methylimidazol-2-yl)-bis(3,5-dimethyl-4-(trimethylsilyl)ethynylpyrazol-1-yl)methane (33) (40.0 mg, 0.0839 mmol) was dissolved in a mixture of tetrahydrofuran (5 mL) and methanol (10 mL). The resulting solution was treated with potassium carbonate (116 mg, 0.839 mmol) and stirred over night at room temperature. After this time, all volatiles were removed in vacuo and the residue was redissolved in dichloro-

200 6.3 4-Ethynyl Substituted Bis(pyrazolyl)methane Ligands methane (30 mL) and the resulting solution was washed with water (3 × 30 mL). Subse- quently, the organic phase was dried (sodium sulfate) and the solvent was removed.

Yield: 22.0 mg (0.0663 mmol, 79 %)

1 ◦ 3 5 H NMR (300 MHz, CDCl3, 25 C): δ = 2.21 (s, 6 H, C -CH 3), 2.24 (s, 6 H, C -CH 3),

3.19 (s, 2 H, C≡C-H), 3.34 (s, 3 H, Nimid-CH 3), 6.93 (s, 1 H, Cimid-H), 7.05 (s, 1 H,

Cimid-H), 7.54 (s, 1 H, CbridgeH) ppm.

13 ◦ 3 5 C NMR (75.5 MHz, CDCl3, 25 C): δ = 10.5 (C -CH3), 12.5 (C -CH3), 30.0 (Nimid- 4 CH3), 70.2 (Cbridge), 75.3 (C≡C), 81.4 (C≡C), 103.4 (C ), 123.1 (Cimid), 128.0 (Cimid), 3 5 140.0 (C ), 144.7 (C ), 150.9 (Cimid) ppm.

ESI MS: m/z (%) = 355.16 (100) [M+Na]+, 687.34 (45) [2M+Na]+.

−1 IR (KBr): νe = 3261 (s, C≡C-H), 2118 (m, C≡C), 1554 (m, C=N) cm .

201 6 Experimental Section

6.4 Coordination Polymers of 1,4-Bis(1H-pyrazol-4- yl)butadiynes

6.4.1 Synthesis of 3,5-Dimethyl-4-ethynyl-1-tritylpyrazole (35)

A solution of 3,5-dimethyl-4-(trimethylsilylethynyl)-1-tritylpyrazole (59) (4.00 g, 9.20 mmol) in a mixture of tetrahydrofuran and methanol (1:1 v/v) was treated with potassium carbonate (6.36 g, 46.0 mmol) and stirred over night. Subsequently the solvent was removed in vacuo and the remaining residue was dissolved in dichloromethane (100 mL) and water (100 mL). The organic phase was washed with water two more times and dried (sodium sulfate). Finally the solvent was removed in vacuo. The product was used without further puriﬁcation

N N

C26H22N2 MW: 362.48 g/mol

Yield: 2.95 g (8.14 mmol, 89 %)

1 ◦ 5 3 H NMR (300 MHz, CDCl3, 25 C): δ = 1.37 (s, 3 H, C -CH3), 2.06 (s, 3 H, C -CH3), 3.02 (s, 1 H, C≡C-H), 6.99 (m, 15 H, Trt) ppm.

13 ◦ 5 3 C NMR (75.5 MHz, CDCl3, 25 C): δ = 12.9 (C -CH3), 13.8 (C -CH3), 78.5 (C≡C), 81.2 (C≡C), 103.3 (C4), 127.3 (Trt), 127.5 (Trt), 130.3 (Trt), 142.8 (Trt), 145.6 (C3), 5 148.1 (C ) ppm. (C-(C6H5)3) could not be resolved.

Elemental analysis of C26H22N2 (362.48 g/mol): calcd. C 86.15, N 7.73, H 6.12; found C 85.60, N 7.41, H 6.10 %.

202 6.4 Coordination Polymers of 1,4-Bis(1H-pyrazol-4-yl)butadiynes

6.4.2 Synthesis of 1,4-Bis(3,5-dimethyl-1-tritylpyrazole-4-yl)butadiyne (36)

To a solution of 4-ethynyl-3,5-dimethyl-1-tritylpyrazole (35) (6.85 g, 18.9 mmol) in a 3:1 (v/v) mixture of acetonitrile and pyridine (150 mL) was added copper(II) acetate (2.52 g, 12.6 mmol) and the resulting mixture was heated to reﬂux for two hours. After this time, the reaction was cooled down to ambient temperature and stirred for another 24 hours. Subsequently it was extracted with ethyl acetate (200 mL) and the organic phase was washed thoroughly with water until the disappearance of the blue copper color. The solvent was removed, the residue was washed with acetone to remove remaining impurities and the product was dried in vacuo.

N N N N

C52H42N4 MW: 722.94 g/mol

Yield: 4.70 g (13.0 mmol, 69 %)

1 ◦ 5 3 H NMR (300 MHz, CD2Cl2, 25 C): δ = 1.57 (s, 3 H, C -CH3), 2.25 (s, 3 H, C -CH3), 7.11 (m, 12 H, Trt), 7.29 (m, 18 H, Trt) ppm.

13 ◦ 5 3 C NMR (75.5 MHz, CD2Cl2, 25 C): δ = 13.2 (C -CH3), 14.4 (C -CH3), 74.8 (C≡C), 79.3 (C≡C), 104.0 (C4), 127.9 (Trt), 128.1 (Trt), 130.8 (Trt), 143.22 (Trt), 147.4 (C5), 3 149.3 (C ) ppm. (C-(C6H5)3) could not be resolved.

ESI MS: m/z (%) = 745.33 (100) [M+Na]+, 1468.67 (55) [2M+Na]+.

−1 IR (KBr): νe = 2144 (w, C≡C), 1560 (w, C=N) cm .

203 6 Experimental Section

6.4.3 Synthesis of 1,4-Bis(3,5-dimethyl-1H-pyrazol-4-yl)butadiyne (37)

1,4-Bis(3,5-dimethyl-1-tritylpyrazole-4-yl)butadiyne (36) (1.12 g, 1.55 mmol) was dissolved in a mixture of water and dichloromethane (1:50 v/v, 102 mL) and treated with trifluoroacetic acid (0.263 mL, 3.41 mmol). The resulting solution was stirred for 24 hours at ambient temperature. The product forms a precipitate, which is filtered off and washed thoroughly with water and chloroform before it is dried in vacuo. Crystals suitable for an X-ray structure determination could be obtained by layering a solution of 37 in methanol with n-hexane.

HN NH N N

C14H14N4 MW: 238.29 g/mol

Yield: 0.218 g (0.915 mmol, 59 %)

1 ◦ 5 3 H NMR (300 MHz, acetone-d6, 25 C): δ = 2.28 (s, 6 H, C -CH3 and C -CH3) ppm.

1 ◦ 5 3 H NMR (300 MHz, DMSO-d6, 25 C): δ = 2.17 (s, 3 H, C -CH3), 2.25 (s, 3 H, C -CH3), 12.62 (s, 1 H, NH) ppm.

13 ◦ 5 3 C NMR (75.5 MHz, DMSO-d6, 25 C): δ = 10.0 (C -CH3), 12.5 (C -CH3), 97.5 (C≡C), 98.3 (C≡C), 105.5 (C4), 144.1 (C5), 150.7 (C3) ppm.

Elemental analysis of C14H14N4 (238.29 g/mol): calcd. C 70.57, H 5.92, N 23.51; found C 70.18, H 6.17, N 22.84 %.

ESI MS: m/z (%) = 239.13 (100) [MH]+, 261.11 (30) [M+Na]+.

−1 IR (KBr): νe = 3172 (m, N-H), 2152 (w, C≡C), 1550 (w, C=N), 1243 (vs, C-C) cm .

204 6.4 Coordination Polymers of 1,4-Bis(1H-pyrazol-4-yl)butadiynes

6.4.4 Synthesis of Poly(cobalt(II)acetylacetonato-bis(1,4-bis(3,5- dimethylpyrazol-4-yl)butadiyne)) (38/39)

A solution of 1,4-bis(3,5-dimethyl-1H -pyrazol-4-yl)butadiyne (37) (38.0 mg, 0.159 mmol) in acetone (20 mL) was added to a solution of cobalt(II) acetylacetonate (40.9 mg, 0.159 mmol) in acetone (20 mL). A violet solid immediately precipitated and was collected by ﬁltration. The crude product was thoroughly washed with acetone and subsequently dried in vacuum. Crystals suitable for an X-ray structure determination could be obtained by slow evaporation of a highly diluted solution of 37 and cobalt(II) acetylacetonate (39).

O O Co N N N N Co O O

n 38

(C24H26Co2N4O4)n MW: 552.36 g/mol

Yield: 35.1 mg (63.5 µmol, 40 %)

Elemental analysis of C24H26Co2N4O4 (552.36): calcd. C 52.00, N 10.11, H 5.09; found C 52.01, N 10.01, H 4.70 %.

IR (KBr): νe = 2143 (m, C≡C), 1580 (s, acetylacetonate), 1519 (vs, acetylacetonate), 1428 (s, acetylacetonate), 1266 (m, acetylacetonate) cm−1

205 6 Experimental Section

6.4.5 Synthesis of Poly(cobalt(II)chlorido-bis(1,4-bis(3,5-dimethyl- 1H-pyrazol-4-yl)butadiyne)) (40)

A solution of 1,4-bis(3,5-dimethyl-1H -pyrazol-4-yl)butadiyne (37) (38.0 mg, 0.159 mmol) in acetone (20 mL) was added to a solution of cobalt(II) chloride (37.9 mg, 0.159 mmol) in acetone (20 mL). The resulting solution was stirred under reﬂux for 24 hours. During this time, a blue precipitate was formed, which was subsequently collected via ﬁltration. The crude product was thoroughly washed with acetone and subsequently dried in vacuum. The material was obtained as a microcrystalline powder, which crystallized containing acetone.

HN NH O Cl x 0.5 N N Co Cl n 40

(C14H14Cl2CoN4)n MW: 368.13 g/mol

Yield: 51.2 mg (0.139 mmol, 87 %)

Elemental analysis of C14H14CoN4 (× 0.5 eq. acetone) (368.13): calcd. C 46.87, N 14.11, H 4.31; found C 46.90, N 14.00, H 4.43 %.

−1 IR (KBr): νe = 3258 (s, N-H), 2151 (m, C≡C), 1567 (s, C=N) cm .

206 6.4 Coordination Polymers of 1,4-Bis(1H-pyrazol-4-yl)butadiynes

6.4.6 Attempted synthesis of Poly(cobalt(II)bromido-bis(1,4-bis(3,5- dimethyl-1H-pyrazol-4-yl)butadiyne)) (41)

A solution of 1,4-bis(3,5-dimethyl-1H -pyrazol-4-yl)butadiyne (37) (38.0 mg, 0.159 mmol) in acetone (20 mL) was added to a solution of cobalt(II) bromide (52.0 mg, 0.159 mmol) in acetone (20 mL). The resulting solution was stirred under reﬂux for 24 hours. After this time, no precipitate was formed.

HN NH Br N N Co Br n 41

(C14H14Br2CoN4)n MW: 457.04 g/mol

In an alternative attempt, acetone was exchanged by acetontrile and the resulting solution stirred for 24 hours under reﬂux. As before, no precipitate was formed and no hints for a successful reaction could be found.

207 6 Experimental Section

6.4.7 Synthesis of 4-Ethynyl-1-tritylpyrazole (42)

4-(Trimethylsilyl)ethynyl-1-tritylpyrazole (27) (1.00 g, 2.46 mmol) was dissolved in a mixture of tetrahydrofuran and methanol (1:2 v/v, 50 mL) and treated with potassium ﬂuoride (2.86 g, 49.2 mmol). The resulting solution was stirred for 48 hours at room temperature. After this time, all volatiles were removed and the residue was suspended in a saturated solution of sodium bicarbonate. The suspension was extracted with diethyl ether (3 × 50 mL), the combined organic phases were dried (sodium sulfate) and the solvent was removed in vacuo.

N N

C24H18N2 MW: 334.42 g/mol

Yield: 0.600 g (1.80 mmol, 73 %)

1 ◦ H NMR (300 MHz, CDCl3, 25 C): δ = 3.01 (s, 1 H, C≡C-H), 7.17 (m, 6 H, Trt), 7.35 (m, 9 H, Trt), 7.59 (s, 1 H, C3-H), 7.60 (s, 1 H, C5-H) ppm.

13 ◦ C NMR (75.5 MHz, CDCl3, 25 C): δ = 75.4 (C≡C), 78.3 (C≡C), 79.1 (Trt), 100.8 (C4), 127.8 (Trt), 127.9 (Trt), 130.1 (Trt), 135.9 (Trt), 142.5 (C3), 142.6 (C5) ppm.

Elemental analysis of C24H18N2 (334.42 g/mol): calcd. C 86.20, H 5.43, N 8.38; found C 86.19, H 5.45, N 8.34 %.

ESI MS: m/z (%) = 243.12 (100) [Trt]+, 357.14 (100) [M+Na]+, 691.28 (72) [2M+Na]+.

−1 IR (KBr): νe = 3284 (m, cch), 2165 (w, C≡C), 1544 (w, C=N) cm .

208 6.4 Coordination Polymers of 1,4-Bis(1H-pyrazol-4-yl)butadiynes

6.4.8 Synthesis of 1,4-Bis(1-tritylpyrazol-4-yl)butadiyne (43)

To a solution of 4-ethynyl-1-tritylpyrazole (42) (1.29 g, 3.85 mmol) in a 3:1 v/v mixture of acetonitrile and pyridine (160 mL) was added copper(II) acetate (1.92 g, 9.63 mmol). The resulting suspension was heated to reﬂux (85 ◦C) for two hours. After this time, the reaction was allowed to cool to room temperature and the stirring was continued for 24 hours. All volatiles were removed and the residue was extracted with dichloromethane (100 mL) in an ultrasonic bath. The organic phase was ﬁltrated, washed with water (4 × 50 mL) and dried (sodium sulfate).

N N N N

C48H34N4 MW: 666.83 g/mol

Yield: 0.847 g (1.27 mmol, 66 %)

1 ◦ H NMR (300 MHz, CDCl3, 25 C): δ = 7.14 (m, 6 H, Trt), 7.33 (m, 6 H, Trt), 7.58 (s, 1 H, C5-H), 7.78 (s, 1 H, C3-H) ppm.

13 ◦ C NMR (75.5 MHz, CDCl3, 25 C): δ = 72.8 (C≡C), 74.8 (C≡C), 79.3 (C-Trt3), 100.8 (C4), 127.9 (Trt), 128.0 (Trt), 130.1 (Trt), 136.6 (Trt), 142.4 (C5), 142.9 (C3) ppm.

Elemental analysis of C48H34N4 (666.83 g/mol): calcd. C 86.46, N 8.10, H 5.02; found C 84.91, N 8.10, H 5.02 %.

ESI MS: m/z (%) = 689.26 (100) [M+Na]+, 1356.54 (10) [2M+Na]+.

−1 IR (KBr): νe = 2151 (w, C≡C), 1539 (s, C=N) cm .

209 6 Experimental Section

6.4.9 Attempted Synthesis of 1,4-Bis(1H-pyrazol-4-yl)butadiyne (44)

A mixture of 1,4-bis(1-tritylpyrazol-4-yl)butadiyne (43) (200 mg, 0.300 mmol) in dichloromethane (10 mL) was treated with boron tribromide (0.301 mg, 1.20 mmol). The resulting solution was stirred for 24 hours at room temperature. Subsequently, all volatiles were removed in vacuo and the remaining residue was extracted with chloroform.

HN NH N N 44

C10H6N4 MW: 182.19 g/mol

1 ◦ H NMR (300 MHz, CD2Cl2, 25 C): δ = 7.31 (s, 4 H) ppm.

13 ◦ C NMR (75.5 MHz, CD2Cl2, 25 C): δ = 82.8, 127.7, 127.8, 130.6, 145.6 ppm.

−1 IR (KBr): νe = 2208 (w), 1958 (w) cm .

210 6.5 Ferrocene Based Models for Rieske Dioxygenases

6.5 Ferrocene Based Models for Rieske Dioxygenases

6.5.1 Synthesis of Bis(4-iodo-3,5-dimethylpyrazol-1-yl)methane (45)

To a solution of 4-iodo-3,5-dimethylpyrazole (23) (5.00 g, 22.5 mmol) in dichloromethane (250 mL) were added potassium hydroxide (4.55 g, 81.1 mmol), potassium carbonate (11.2 g, 81.1 mmol) and benzyltriethylammonium chloride (0.462 g, 2.03 mmol). The resulting suspension was heated to reflux for 48 hours. After this time, the solids were filtered off and the remaining solution was washed with water (3 × 250 mL) before it was dried (sodium sulfate). The solvent was removed in vacuo.

N N I I N N

C11H14I2N4 MW: 456.06 g/mol

Yield: 2.65 g (5.81 mmol, 52 %)

1 ◦ 3 5 H NMR (300 MHz, CDCl3, 25 C): δ = 2.19 (s, 6 H, C -CH3), 2.47 (s, 6 H, C -CH3),

6.14 (s, 2 H, -CH2-) ppm.

13 ◦ 5 3 4 C NMR (75.5 MHz, CDCl3, 25 C): δ = 12.2 (C -CH3), 14.0 (C -CH3), 62.0 (C ), 5 3 65.1 (-CH2-), 142.1 (C ), 150.4 (C ) ppm.

Elemental analysis of C11H14I2N4 (456.06 g/mol): calcd. C 28.97, N 12.29, H 3.09; found C 30.39, N 12.39, H 3.24 %.

ESI MS: m/z (%) = 478.20 (100) [M+Na]+, 934.85 (35) [2M+Na]+.

−1 IR (KBr): νe = 1539 (s, C=N) cm .

211 6 Experimental Section

6.5.2 Synthesis of Bis(4-iodopyrazol-1-yl)methane (46)

Attempted synthesis To a solution of 4-iodopyrazole (22) (10.0 g, 51.6 mmol) in dichloromethane (250 mL) were added potassium hydroxide (10.5 g, 186 mmol), potassium carbonate (25.7 g, 186 mmol) and benzyltriethylammonium chloride (1.18 g, 5.16 mmol). The resulting suspension was heated to reﬂux for 24 hours. After this time, all volatiles were removed and the residue was taken up in ethyl acetate (250 mL) and water (250 mL). The phases were seperated and the organic phase was washed with water (2 × 250 mL) before it was dried (sodium sulfate). The solvent was removed in vacuo. The remaining residue was thoroughly washed with acetone. While the desired product bis(4-iodopyrazol-1-yl)methane (46) could only be obtained in traces, the acetone phase contained signiﬁcant amounts of bis(4-iodopyrazol-1-yl)acetic acid (47).

Yield: 0.270 g (0.675 mmol, 3 %)

Successful synthesis To a solution of bis(pyrazol-1-yl)methane (10.0 g, 67.2 mmol) and iodine (20.4 g, 80.4 mmol) in acetonitrile (150 mL) was slowly added cer(IV)ammoniumnitrate (36.8 g, 33.6 mmol). After vigorous stirring for three hours, all volatiles were removed in vacuo and the remaining residues were dissolved in ethyl acetate (150 mL) and water (150 mL). Subsequently, a saturated solution of sodium thiosulfate was slowly added until the iodine color disappeared. The phases were separated and the organic phase was washed with brine (2 × 150 mL) and dried (sodium sulfate). The solvent was removed in vacuo and the obtained compound was dried in vacuum.

N N I I N N 46

C7H6I2N4 MW: 399.96 g/mol

Yield: 21.0 g (52.4 mmol, 78 %)

1 ◦ 3 H NMR (300 MHz, CDCl3, 25 C): δ = 6.24 (s, 2 H, -CH2-), 7.56 (s, 2 H, C H), 7.69 (s, 2 H, C5H) ppm.

13 ◦ 4 3 C NMR (75.5 MHz, CDCl3, 25 C): δ = 58.6 (C ), 65.3 (-CH2-), 134.0 (C ), 147.1 (C5) ppm.

Elemental analysis of C7H6I2N4 (399.96 g/mol): calcd. C 21.02, N 14.01, H 1.51; found

212 6.5 Ferrocene Based Models for Rieske Dioxygenases

C 20.61, N 13.41, H 1.51 %.

ESI MS: m/z (%) = 398.86 (100) [M-H]−.

−1 IR (KBr): νe = 1513 (m, C=N) cm .

6.5.3 Synthesis of Bis(4-iodopyrazol-1-yl)acetic acid (47)

A solution of 4-iodopyrazole (22) (4.80 g, 24.1 mmol) in tetrahydrofuran (150 mL) was treated with potassium hydroxide (3.97 g, 74.8 mmol), potassium carbonate (10.3 g, 74.8 mmol), benzyltriethylammonium chloride (0.593 g, 2.50 mmol) and dibromoacetic acid (2.72 g, 12.5 mmol). The suspension was heated to reﬂux and stirred over night. Afterwards, all volatiles were removed in vacuo and the remaining residue was redissolved in water (100 mL). The resulting solution was neutralized with half concentrated hydrochloric acid and extracted with diethyl ether (3 × 100 mL) to remove impurities. Subsequently, the aqueous phase was acidiﬁed to pH 1 and once again extracted with diethyl ether (3 × 100 mL). The combined organic phases were dried (sodium sulfate) and the solvent was removed in vacuo.

O OH

N N I I N N 47

C8H6I2N4O2 MW: 443.97 g/mol

Yield: 2.76 g (6.22 mmol, 50 %)

1 ◦ 5 H NMR (300 MHz, CD3CN, 25 C): δ = 7.22 (s, 1 H, CbridgeH), 7.60 (s, 2 H, C -H), 7.93 (s, 2 H, C3-H) ppm.

13 ◦ 4 5 C NMR (75.5 MHz, CD3CN, 25 C): δ = 59.4 (C ), 75.3 (Cbridge), 136.6 (C ), 147.2 3 (C ), 165.6 (-CO2H) ppm.

Elemental analysis of C8H6I2N4O2 (443.97 g/mol): calcd. C 21.64, N 12.62, H 1.36; found C 22.41, N 12.75, H 1.53 %.

− − ESI MS: m/z (%) = 398.86 (80) [M-CO2H] , 442.85 (100) [M-H] .

−1 IR (KBr): νe = 1719 (s, CO2H), 1517 (m, C=N) cm .

213 6 Experimental Section

6.5.4 Synthesis of Bis(4-iodo-3,5-dimethylpyrazol-1-yl)acetic acid (48)

A solution of 4-iodo-3,5-dimethylpyrazole (23) (15.0 g, 67.5 mmol) in tetrahydrofuran (300 mL) was treated with potassium hydroxide (13.7 g, 243 mmol), potassium carbonate (33.6 g, 243 mmol), benzyltriethylammonium chloride (1.39 g, 6.09 mmol) and dibromoacetic acid (7.38 g, 33.9 mmol). The suspension was heated to reflux and stirred over night. Afterwards, all volatiles were removed in vacuo and the remaining residue was redissolved in water (100 mL). The resulting solution was extracted with diethyl ether (3 × 100 mL) to remove impurities. Subsequently, the aqueous phase was acidified to pH 2 and once again extracted with diethyl ether (3 × 100 mL). The combined organic phases were dried (sodium sulfate) and the solvent was removed in vacuo. The product was used without further purification.

O OH

N N I I N N

C12H14I2N4O2 MW: 500.07 g/mol

Yield: 10.2 g (20.4 mmol, 60 %)

1 ◦ 3 5 H NMR (300 MHz, CDCl3, 25 C): δ = 2.24 (s, 6 H, C -CH3), 2.26 (s, 6 H, C -CH3)

7.00 (s, 1 H, CbridgeH) ppm.

13 ◦ 3 5 4 C NMR (75.5 MHz, CDCl3, 25 C): δ = 12.3 (C -CH3), 14.1 (C -CH3), 67.1 (C ), 3 5 71.9 (Cbridge), 143.1 (C ), 151.3 (C ), 164.5 (CO2H) ppm.

214 6.5 Ferrocene Based Models for Rieske Dioxygenases

6.5.5 Synthesis of Methyl bis(4-iodopyrazol-1-yl)acetate (49)

A solution of bis(4-iodopyrazol-1-yl)acetic acid (60) (1.00 g, 2.25 mmol) in methanol (100 mL) was treated with concentrated sulfuric acid (0.160 mL, 2.86 mmol). The reaction mixture was stirred for 72 hours at room temperature. After this time, the solvent was distilled oﬀ and the residue redissolved in diethyl ether (100 mL). The solution was washed with a saturated solution of sodium bicarbonate (3 × 100 mL) and dried afterwards (sodium sulfate). Subsequently all volatiles were removed in vacuo.

O O

N N I I N N 49

C9H8I2N4O2 MW: 458.00 g/mol

Yield: 426 mg (0.930 mmol, 41 %)

1 ◦ H NMR (300 MHz, CDCl3, 25 C): δ = 3.89 (s, 3 H, CH3), 7.00 (s, 1 H, CbridgeH), 7.60 (s, 2 H, C3-H), 7.80 (s, 2 H, C5-H) ppm.

13 ◦ 4 C NMR (75.5 MHz, CDCl3, 25 C): δ = 54.1 (CH3), 59.1 (C ), 74.3 (Cbridge), 134.5 3 5 (C ), 146.2 (C ), 163.9 (CO2) ppm.

Elemental analysis of C9H8I2N4O2 (458.00 g/mol): calcd. C 23.60, N 12.23, H 1.76; found C 24.38, N 11.72, H 2.02 %.

ESI MS: m/z (%) = 480.86 (100) [M+Na]+, 938.73 (10) [2M+Na]+.

−1 IR (KBr): νe = 1756 (vs, CO2H), 1513 (m, C=N) cm .

215 6 Experimental Section

6.5.6 Synthesis of Methyl bis(4-iodopyrazol-1-yl)acetate (50)

A solution of bis(4-iodo-3,5-dimethylpyrazol-1-yl)acetic acid (48) (1.18 g, 2.36 mmol) was dissolved in methanol (150 mL) and treated with concentrated hydrochloric acid (1.00 mL). The resulting mixture was stirred for 72 hours at room temperature. Subse- quently all volatiles were removed in vacuo and the remaining residue was redissolved in diethyl ether (100 mL) and washed with a saturated solution of sodium bicarbonate (3 × 100 mL). The organic phase was dried (sodium sulfate) and the solvent was distilled oﬀ.

O O

N N I I N N

C13H16I2N4O2 MW: 514.10 g/mol

Yield: 0.622 g (1.21 mmol, 51 %)

1 ◦ 3 5 H NMR (300 MHz, CDCl3, 25 C): δ = 2.21 (s, 6 H, C -CH3), 2.23 (s, 6 H, C -CH3)

3.89 (s, 3 H, CO2-CH3), 7.01 (s, 1 H, CbridgeH) ppm.

13 ◦ 3 5 C NMR (75.5 MHz, CDCl3, 25 C): δ = 12.3 (C -CH3), 14.1 (C -CH3), 53.7 (CO2- 4 3 5 CH3), 68.0 (C ), 74.0 (Cbridge), 142.7 (C ), 150.7 (C ), 164.5 (CO2) ppm.

Elemental analysis of C13H16I2N4O2 (514.10 g/mol): calcd. C 30.37, N 10.90, H 3.14; found C 30.74, N 10.81, H 3.17 %.

ESI MS: m/z (%) = 536.93 (100) [M+Na]+, 1050.87 (45) [2M+Na]+.

−1 IR (KBr): νe = 1764 (vs, CO2H), 1550 (m, C=N) cm .

216 6.5 Ferrocene Based Models for Rieske Dioxygenases

6.5.7 Synthesis of Bis(4-ethynylferrocenylpyrazol-1-yl)methane (51)

A solution of bis(4-iodopyrazol-1-yl)methane (46) (100 mg, 0.275 mmol) in tetrahydrofuran (50 mL) was treated with bis(triphenylphosphine)palladium dichloride (19.3 mg, 0.0275 mmol), copper(I) iodide (5.24 mg, 0.0275 mmol) and ethynylferrocene (116 mg, 0.550 mmol). After the addition of triethylamine (10 mL), the solution was heated to 60 ◦C and stirred at this temperature for 48 hours. After this time, all volatiles were distilled oﬀ and the remaining residue was puriﬁed via column chromatography (silica, n-hexane:ethyl acetate 9:1 v/v). The second colored fraction yielded 51 as an orange powder after removal of the solvent. Crystals suitable for an X-ray structure determination could be obtained by slowly evaporating a solution of 51 in ethyl acetate and n-hexane.

N N N N Fe Fe

C31H24Fe2N4 MW: 564.25 g/mol

Yield: 90.0 mg (0.160 mmol, 58 %)

1 ◦ H NMR (300 MHz, CDCl3, 25 C): δ = 4.22 (s, 4 H, C5H4), 4.23 (s, 10 H, Cp), 4.45 3 5 (s, 4 H, C5H4), 6.23 (s, 2 H, -CH2-), 7.66 (s, 2 H, C ), 7.78 (s, 2 H, C ) ppm.

13 ◦ C NMR (75.5 MHz, CDCl3, 25 C): δ = 65.1 (C Fc-C≡C or -CH2-), 65.5 (C Fc-C≡C or 4 -CH2-), 68.7 (C5H4), 69.9 (Cp), 71.2 (C5H4), 75.6 (C≡C), 89.4 (C≡C), 105.9 (C ), 131.8 (C5), 143.2 (C3) ppm.

Elemental analysis of C31H24Fe2N4 (564.25 g/mol): calcd. C 65.99, N 9.93, H 4.29; found C 66.19, N 9.58, H 4.33 %.

ESI MS: m/z (%) = 564.07 (25) [M]+, 565.08 (22) [MH]+, 587.06 (100) [M+Na]+.

−1 IR (KBr): νe = 2225 (w, C≡C), 1764 (vs, CO2H), 1563 (m, C=N) cm .

217 6 Experimental Section

6.5.8 Synthesis of Methyl bis(4-ethynylferrocenylpyrazol-1-yl)acetate (52)

A solution of methyl bis(4-iodopyrazol-1-yl)acetate (49) (119 mg, 0.238 mmol) in tetrahydrofuran (20 mL) was treated with bis(triphenylphosphine)palladium dichloride (16.7 mg, 0.0238 mmol), copper(I) iodide (4.53 mg, 0.0238 mmol) and ethynylferrocene (100 mg, 0.476 mmol). After the addition of triethylamine (5 mL), the solution was heated to 60 ◦C and stirred at this temperature for 24 hours. After this time, all volatiles were distilled oﬀ and the remaining residue was puriﬁed via column chromatography (silica, n-hexane:ethyl acetate 7:3 v/v). The second colored fraction yielded 51 as an orange powder after removal of the solvent.

O O

N N N N Fe Fe

C33H26Fe2N4O2 MW: 622.29 g/mol

Yield: 44.0 mg (70.7 µmol, 30 %)

1 ◦ H NMR (300 MHz, CDCl3, 25 C): δ = 3.91 (s, 3 H, -CO2CH3), 4.23 (s, 4 H, C5H4), 3 4.24 (s, 10 H, Cp), 4.46 (s, 4 H, C5H4), 6.99 (s, 1 H, CbridgeH), 7.70 (s, 2 H, C H), 7.88 (s, 2 H, C5H) ppm.

13 ◦ C NMR (75.5 MHz, CDCl3, 25 C): δ = 54.0 (CO2-CH3), 68.8 (C5H4), 69.9 (Cp), 4 71.3 (C5H4), 74.6 (Cbridge), 75.4 (C Fc-C≡C), 82.8 (C≡C), 106.2 (C≡C), 132.3 (C ), 143.4 3 5 (C ), 146.8 (C ), 164.0 (CO2) ppm.

Elemental analysis of C33H26Fe2N4O2 (622.29 g/mol): calcd. C 63.69, N 9.00, H 4.21; C 61.71, N 8.93, H 4.26 %.

ESI MS: m/z (%) = 622.07 (20) [M]+, 623.08 (15) [MH]+, 645.06 (100) [M+Na]+, 661.04 (50) [M+K]+.

−1 IR (KBr): νe = 2225 (w, C≡C), 1566 (m, C=N) cm .

218 6.5 Ferrocene Based Models for Rieske Dioxygenases

6.5.9 Synthesis of Bis((4-ethynyl-1-ferrocenylphen-4-yl)-3,5- dimethylpyrazol-1-yl)methane (53)

A solution of bis(4-iodo-3,5-dimethylpyrazol-1-yl)methane (bedmpzm) (15) (160 mg, 0.439 mmol) and 4-(ferrocenyl)-phenylacetylene (400 mg, 1.76 mmol) in a mixture of dimethylformamide (30 mL) and triethylamine (10 mL) was treated with bis(triphenylphosphine)palladium dichloride (30.8 mg, 0.0439 mmol) and copper(I) iodide (8.36 mg, 0.0439 mmol). The reaction was heated to 65 ◦C and stirred for 24 hours. After this time, all volatiles were distilled oﬀ and the remaining residue was puriﬁed via column chromatography (silica, 1. n-hexane:ethyl acetate 8:2 v/v, 2. n-hexane:ethyl acetate 7:3 v/v). The second colored fraction yielded 61 as a brownish oil after removal of the solvent. By precipitation from dichloromethane with n-pentane, the desired product could be obtained as an orange powder.

N N N N Fe Fe

C47H40Fe2N4 MW: 772.55 g/mol

Yield: 39.0 mg (51.0 µmol, 5.80 %)

1 ◦ 3 5 H NMR (300 MHz, CDCl3, 25 C): δ = 2.31 (s, 6 H, C -CH3), 2.57 (s, 6 H, C -CH3),

4.05 (s, 10 H, Cp), 4.35 (s, 4 H, C5H4), 4.67 (s, 4 H, C5H4), 6.09 (s, 2 H, -CH2-), 7.39 (d, 3 3 2 H, J H,H = 8.29 Hz, phenylene), 7.44 (d, 2 H, J H,H = 8.48 Hz, phenylene) ppm.

13 ◦ 3 5 C NMR (75.5 MHz, CDCl3, 25 C): δ = 10.8 (C -CH3), 12.6 (C -CH3), 61.0 (-CH2-),

66.5 (C5H4), 69.3 (C5H4), 69.7 (Cp), 80.2 (C Fc-C6H4), 84.3 (C≡C), 93.5 (C≡C), 103.7 (C4), 120.8 (phenylene), 125.8 (phenylene), 131.3 (phenylene), 139.4 (phenylene), 143.2 (C3), 150.6 (C5) ppm.

Elemental analysis of C47H40N4Fe2 (772.54): calcd. C 73.07, H 5.22, N 7.25; found C 71.18, H 4.98, N 5.82 g/mol.

ESI MS: m/z (%) = 772.19 (24) [M]+, 773.20 (21) [MH]+, 795.18 (100) [M+Na]+, 1568.38 (17) [2M+Na]+.

219 6 Experimental Section

−1 IR (CH2Cl2): νe = 2213 (w, C≡C), 1523 (m, cn) cm .

6.5.10 Synthesis of Methyl bis((4-ethynyl-1-ferrocenylphen-4- yl)pyrazol-1-yl)acetate (54)

A solution of methyl bis(4-iodopyrazol-1-yl)acetate (49) (150 mg, 0.341 mmol) and 4- (ferrocenyl)-phenylacetylene (292 mg, 1.02 mmol) in a mixture of dimethylformamide (30 mL) and triethylamine (10 mL) was treated with bis(triphenylphosphine)palladium dichloride (23.9 mg, 0.0341 mmol) and copper(I) iodide (6.49 mg, 0.0341 mmol). The reaction was heated to 65 ◦C and stirred for 24 hours. After this time, all volatiles were distilled oﬀ and the remaining residue was puriﬁed via column chromatography (silica, 1. n-hexane:ethyl acetate 8:2 v/v, 2. n-hexane:ethyl acetate 7:3 v/v). The second colored fraction yielded 62 as a brownish oil after removal of the solvent. By precipitation from dichloromethane with n-pentane, the desired product could be obtained as an orange powder.

O O

N N N N Fe Fe

C45H34Fe2N4O2 MW: 774.48 g/mol

Yield: 95.3 mg (0.123 mmol, 24 %)

1 ◦ H NMR (300 MHz, CDCl3, 25 C): δ = 3.93 (s, 3 H, CO2-CH3), 4.05 (s, 10 H, Cp), 4.36 3 (s, 4 H, C5H4), 4.66 (s, 4 H, C5H4), 7.02 (s, 1 H, -CH-), 7.40 (d, 2 H, J H,H = 8.10 Hz, 3 3 phenylene), 7.44 (d, 2 H, J H,H = 8.48 Hz, phenylene), 7.75 (s, 2 H, C -H), 7.95 (s, 2 H, C5-H) ppm.

13 ◦ C NMR (75.5 MHz, CDCl3, 25 C): δ = 30.0 (CO2-CH3), 54.1 (-CH-), 66.5 (C5H4), 4 68.5 (C Fc-C6H4), 69.3 (C5H4), 69.7 (Cp), 82.9 (C≡C), 105.9 (C≡C), 120.1 (C ), 125.8 (phenylene), 131.4 (phenylene), 132.6 (phenylene), 135.7 (phenylene), 139.9 (C3), 143.4 5 (C ), 156.7 (CO2) ppm.

Elemental analysis of C45H34Fe2N4O2 (774.48 g/mol): calcd. C 69.79, H 4.43, N 7.23;

220 6.5 Ferrocene Based Models for Rieske Dioxygenases found C 67.92, H 4.24, N 6.30.

ESI MS: m/z (%) = 774.14 (31) [M]+, 775.14 (17) [MH]+, 797.13 (100) [M+Na]+, 1572.27 (11) [2M+Na]+.

−1 IR (KBr): νe = 2143 (w, C≡C), 1717 (vs, CO2H), 1522 (w, C=N) cm .

6.5.11 Synthesis of Bis(3,5-dimethyl-4-(1-ferrocenyl-1,2,3-triazol-4- yl)pyrazol-1-yl)methane (55)

Bis(4-ethynylpyrazol-1-yl)methane (15) (50.0 mg, 0.198 mmol) and ferrocene azide (90.0 mg, 0.396 mmol) were dissolved in tetrahydrofuran (30 mL). To this mixture was added a solution of copper sulfate (24.8 mg, 9.92 µmol) and sodium ascorbate (78.6 mg, 0.396 mmol) in water (30 mL). The resulting mixture was stirred for 72 hours. After this time, the solution was extracted with ethyl acetate (3 × 50 mL), the combined organic phases were dried (sodium sulfate) and the solvent removed in vacuo. The crude product was puriﬁed via column chromatography (silica, n-hexane:ethyl acetate 7:3 v/v).

Fe N N N N Fe N N N N N N

C35H34Fe2N10 MW: 706.42 g/mol

Yield: 34.0 mg (48.1 µmol, 24 %)

1 ◦ 3 5 H NMR (300 MHz, CDCl3, 25 C): δ = 2.37 (s, 6 H, C -CH3), 2.73 (s, 6 H, C -CH3),

4.23 (s, 10 H, Cp), 4.28 (s, 4 H, C5H4), 4.87 (s, 4 H, C5H4), 6.25 (s, 2 H, -CH2-), 7.69 (s, 2 H, triazole) ppm.

13 ◦ 3 5 C NMR (75.5 MHz, CDCl3, 25 C): δ = 11.0 (C -CH3), 13.4 (C -CH3), 60.8 (-CH2-),

62.1 (C5H4), 66.7 (C5H4), 70.1 (Cp), 93.7 (C Fc-triazole), 109.7 (triazole), 119.7 (triazole),

139.0 (Cpz), 141.1 (Cpz), 146.8 (Cpz) ppm.

ESI MS: m/z (%) = 707.17 (30) [MH]+.

−1 IR (KBr): νe = 1526 (s, C=N) cm .

221 6 Experimental Section

6.5.12 Synthesis of Bis(3,5-dimethyl-4-(1-methylferrocenyl-1,2,3- triazol-4-yl)pyrazol-1-yl)methane (56)

Bis(4-ethynyl-3,5-dimethylpyrazol-1-yl)methane (15) (0.100 g, 0.396 mmol) and azido- methyl ferrocene (0.210 g, 0.871 mmol) were dissolved in a mixture of dichloromethane (10 mL) and methanol (25 mL). To this mixture were added solutions of copper sulfate (19.8 mg, 7.92 µmol) in water (1.5 mL) and sodium ascorbate (62.8 mg, 0.317 mmol) in water (1.5 mL). The resulting mixture was stirred for 72 hours. After this time, the solvent was removed and the remaining residue was redissolved in water and dichloromethane (1:1 v/v, 50 mL). The aqueous phase was extracted with dichloromethane (3 × 50 mL) and the combined organic phases were again washed with water (1 × 50 mL). Afterwards, they were dried (sodium sulfate) and the solvent was removed in vacuo. The crude product was puriﬁed via column chromatography (silica, 1. n-hexane:ethyl acetate 7:3 v/v, 2. n-hexane:ethyl acetate 3:7 v/v). The fourth colored fraction yielded the desired product as yellow powder after removal of the solvent. Crystals suitable for an X-ray structure determination could be obtained by layering a solution of 56 in ethyl acetate with n- hexane.

N N N N N N N N Fe N N Fe

C37H38Fe2N10 MW: 734.47 g/mol

Yield: 69.0 mg (93.8 µmol, 24 %)

1 ◦ 3 5 H NMR (300 MHz, CDCl3, 25 C): δ = 2.25 (s, 6 H, C -CH3), 2.60 (s, 6 H, C -CH3),

4.16 (s, 10 H, Cp), 4.20 (s, 4 H, C5H4), 4.27 (s, 4 H, C5H4), 5.30 (s, 4 H, CFc-CH2), 6.15

(s, 2 H, -CH2-), 7.37 (s, 2 H, triazole) ppm.

13 ◦ 3 5 C NMR (75.5 MHz, CDCl3, 25 C): δ = 10.8 (C -CH3), 13.1 (C -CH3), 49.9 (CFc-

CH2), 60.8 (-CH2-), 68.7 (C5H4), 68.8 (Cp), 68.9 (C5H4), 81.1 (C Fc-CH2), 109.9 (triazole),

119.7 (triazole), 138.7 (Cpz), 140.8 (Cpz), 146.7 (Cpz) ppm.

Elemental analysis of C37H38N10Fe2 (734.47 g/mol): calcd. C 60.42, H 5.34, N 19.04; found C 59.54, H 5.36, N 18.42 %.

222 6.5 Ferrocene Based Models for Rieske Dioxygenases

ESI MS: m/z (%) = 735.21 (10) [MH]+, 757.19 [M+Na]+, 1492.40 (30) [2M+Na]+.

−1 IR (KBr): νe = 1522 (m, C=N) cm .

223 6 Experimental Section

6.6 Oxygen Atom Transfer Catalysis

An evacuated Schlenk tube was ﬂushed with nitrogen and charged with triphenylphosphine (0.393 g, 1.50 mmol, 200 eq.) and degased dimethyl sulfoxide (10.0 mL). The catalyst (0.05 mol%) was added to the resulting solution and the mixture was stirred for 6 or 24 hours. The samples were analyzed by 1H and 31P NMR spectroscopy. Calculation 31 of yields was done via integration of the OPPh3 signal of the P NMR spectra.

Catalyst t neduct (t0) ncatalyst neduct (t) nproduct (t) y TON TOF [h] [mmol] [µmol] [mmol] [mmol] [%] [10−5 s−1] - 24 1.50 7.50 1.50 0 0 0 0 3 6 1.50 7.50 0.173 0.220 56 112 519 5 6 1.50 7.50 0.177 0.216 55 110 509 P10 24 1.50 7.50 0.0511 0.342 87 174 201 P11 24 1.50 7.50 0.3895 0.0944 1 2 2.31 P12 24 1.50 7.50 0.252 0.142 36 72 83.3 P13 24 1.50 7.50 0.299 0.0944 24 48 55.6 P6-Mo 24 1.50 7.50 0.0433 0.350 89 178 206 P7-Mo 24 1.50 7.50 0.114 0.279 71 142 164 P8-Mo 24 1.50 7.50 0.220 0.173 44 88 102 P9-Mo 24 1.50 7.50 0.362 0.0315 8 16 18.5

Table 6.1: Results of the catalytic reduction of dimethyl sulfoxide.

The results of the catalytic studies are depicted in table 6.1. For reference, the composition of the deployed catalysts is depicted in table 6.2.

Catalyst ligand/complex monomer copolymer

P10 MoO2Cl2(bdmvpzm) (3) MMA

P11 MoO2Cl2(bdmvpzm) (3) EGDMA

P12 MoO2Cl(bdmvpza) (5) MMA

P13 MoO2Cl(bdmvpza) (5) EGDMA P6-Mo bdmvpzm MMA P7-Mo bdmvpzm EGDMA P8-Mo Hbdmvpza MMA P9-Mo Hbdmvpza EGDMA

Table 6.2: Composition of copolymers employed in catalytic DMSO reduction.

224 Appendix

225 Appendix

A Details of Structure Determinations

[MoO2Cl2(bdmvpzm)] (3)

Empirical formula C15H20Cl2MoN4O2 Formula mass [g mol−1] 455.19 Crystal color/habit yellow block Crystal system monoclinic

Space group P 21/a a [Å] 13.6299(8) b [Å] 15.0051(15) c [Å] 8.9003(10) α [◦] 90 β [◦] 90.026(9) γ [◦] 90 V [Å3] 1820.3(3) θ [◦] 6 to 20 h −18 to 18 k −20 to 20 l −12 to 12 F (000),Z 920, 4 −1 µ(Mo-Kα) [mm ] 0.71069 Crystal size [mm] 0.16 × 0.11 × 0.10 −1 Dcalcd. [g cm ], T [K] 1.661, 150 Reflections collected 58192 Independent reflections 5066 Obs. reflections, I > 2σI 4720 Parameter 222 Weight parameter a 0.0369 Weight parameter b 0.0869

R1 (observed) 0.0214

R1 (overall) 0.0255

wR2 (observed) 0.0624

wR2 (overall) 0.0647 Diﬀ. hole / peak [eÅ] −1.254 / 0.372

Table A.1: Details for the structure determination of [MoO2Cl2(bdmvpzm)] (3).

226 A Details of Structure Determinations

1,4-Bis(3,5-dimethyl-1H -pyrazol-4-yl)butadiyne (37)

Empirical formula 2(C14H14N4) × H2O Formula mass [g mol−1] 494.60 Crystal color/habit colorless block Crystal system monoclinic

Space group P 21/c a [Å] 12.7184(14) b [Å] 7.1608(7) c [Å] 14.5737(6) α [◦] 90 β [◦] 106.123(6) γ [◦] 90 V [Å3] 1275.08(19) θ [◦] 6 to 20 h −16 to 16 k −9 to 9 l −18 to 18 F (000),Z 524, 2 −1 µ(Mo-Kα) [mm ] 0.71073 Crystal size [mm] 0.40 × 0.34 × 0.10 −1 Dcalcd. [g cm ], T [K] 1.288, 150 Reflections collected 24081 Independent reflections 2916 Obs. reflections, I > 2σI 2373 Parameter 180 Weight parameter a 0.0689 Weight parameter b 0.5837

R1 (observed) 0.0483

R1 (overall) 0.0624 wR2 (observed) 0.1390 wR2 (overall) 0.1483 Diﬀ. hole / peak [eÅ] −0.322 / 0.091

Table A.2: Details for the structure determination of 1,4-Bis(3,5-dimethyl-1H-pyrazol-4- yl)butadiyne (37).

227 Appendix

Poly(cobalt(II)acetylacetonato-bis(1,4-bis(3,5-dimethyl-1H -pyrazol-4-yl)butadiyne)) (38)

Empirical formula 2(C12H14Co0.5N2O2) × 3 H2O Formula mass [g mol−1] 545.46 Crystal color/habit blue plate Crystal system triclinic Space group P − 1 a [Å] 8.743(3) b [Å] 13.092(3) c [Å] 13.163(9) α [◦] 90.25(6) β [◦] 97.29(3) γ [◦] 97.42(4) V [Å3] 1481.6(12) θ [◦] 2.948 to 27.409 h −11 to 11 k −16 to 16 l −17 to 17 F (000),Z 571, 2 −1 µ(Mo-Kα) [mm ] 0.71073 Crystal size [mm] 0.40 × 0.34 × 0.10 −1 Dcalcd. [g cm ], T [K] 1.2225, 150 Reflections collected 40883 Independent reflections 6782 Obs. reflections, I > 2σI 3793 Parameter 347 Weight parameter a 0.1040 Weight parameter b 1.6398

R1 (observed) 0.0731

R1 (overall) 0.1372

wR2 (observed) 0.1836

wR2 (overall) 0.2336 Diﬀ. hole / peak [eÅ] −0.6583 / 0.9840

Table A.3: Details for the preliminary structure determination of poly(cobalt(II)acetylacetonato-bis(1,4-bis(3,5-dimethyl-1H-pyrazol-4-yl)butadiyne)) (38).

228 A Details of Structure Determinations

Bis(4-ethynylferrocenylpyrazol-1-yl)- methane (51)

Empirical formula C31H24Fe2N4 Formula mass [g mol−1] 564.24 Crystal color/habit brown block Crystal system I b a 2 Space group orthorhombic a [Å] 13.7913(3) b [Å] 18.9209(4) c [Å] 9.25359(18) α [◦] 90 β [◦] 90 γ [◦] 90 V [Å3] 2414.67(9) θ [◦] 3.966 to 73.536 h −15 to 16 k −21 to 23 l −11 to 11 F (000),Z 1160, 4 −1 µ(Cu-Kα) [mm ] 1.54184 Crystal size [mm] 0.4959 × 0.2257 × 0.2257 −1 Dcalcd. [g cm ], T [K] 1.552, 150 Reflections collected 3941 Independent reflections 1916 Obs. reflections, I > 2σI 1834 Parameter 168 Weight parameter a 0.1000 Weight parameter b 0

R1 (observed) 0.0302

R1 (overall) 0.0320

wR2 (observed) 0.0867

wR2 (overall) 0.0897 Diﬀ. hole / peak [eÅ] −0.349 / 0.478

Table A.4: Details for the structure determination of bis(4-ethynylferrocenylpyrazol-1- yl)methane (51).

229 Appendix

Bis(3,5-dimethyl-4-(1-methylferrocenyl-1,2,3-triazol-4-yl)pyrazol-1-yl)methane (56)

Empirical formula 2(C37H38Fe2N10) × H2O Formula mass [g mol−1] 1486.96 Crystal color/habit yellow block Crystal system triclinic Space group P − 1 a [Å] 7.630(2) b [Å] 10.4620(19) c [Å] 21.610(6) α [◦] 92.53(2) β [◦] 98.591(18) γ [◦] 91.61(2) V [Å3] 1703.0(7) θ [◦] 2.73 to 25.19 h −9 to 9 k −12 to 12 l −25 to 25 F (000),Z 774, 1 −1 µ(Mo-Kα) [mm ] 0.71073 Crystal size [mm] 0.18 × 0.13 × 0.12 −1 Dcalcd. [g cm ], T [K] 1.450, 150 Reflections collected 36705 Independent reflections 6114 Obs. reflections, I > 2σI 4006 Parameter 455 Weight parameter a 0.0715 Weight parameter b 10.2974

R1 (observed) 0.0854

R1 (overall) 0.1347

wR2 (observed) 0.1979

wR2 (overall) 0.2332 Diﬀ. hole / peak [eÅ] −1.209 / 0.12

Table A.5: Details for the structure determination of bis(3,5-dimethyl-4-(1-methylferrocenyl-1,2,3-triazol-4-yl)pyrazol-1-yl)methane (56).

230 B Abbreviations

B Abbreviations

∆ Heat

δ Chemical shift in ppm

νe Wavenumber n-BuLi n-Butyllithium iPr iso-Propyl- tBu tert-Butyl-

J Scalar coupling constant in Hz

AAS Atomic absorption spectroscopy

AIBN Azobisisobutyronitrile bdmfcmtpzm Bis(3,5-dimethyl-4-(1-methylferrocenyl-1,2,3-triazol-4-yl)- pyrazol-1-yl)methane bdmfctpzm Bis(3,5-dimethyl-4-(1-ferrocenyl-1,2,3-triazol-4-yl)- pyrazol-1-yl)methane bdmpza Bis(3,5-dimethylpyrazol-1-yl)acetate bdmvpzm Bis(3,5-dimethyl-4-vinylpyrazol-1-yl)methane bdtbpzm Bis(3,5-tert-butylpyrazol-1-yl)methane bedmpzm Bis(4-ethynyl-3,5-dimethylpyrazol-1-yl)methane befcpzm Bis(4-ethynylferrocenylpyrazol-1-yl)methane bepfcdmpzm Bis((4-ethynyl-1-ferrocenylphen-4-yl)-3,5-dimethylpyrazol-1- yl)methane bmip Bis(N -methylimidazol-2-yl)butadiyne

Boc tert-Butyloxycarbonyl br Broad

BTEAC Benzyltriethylammonium chloride

231 Appendix

Bu Butyl calcd. Calculated conc. Concentrated cPMP Cyclic pyranopterin monophosphate

CuAAC Copper(I)-catalyzed azide-alkyne cycloaddition cyt c Ferricytochrome c d Doublet

DMF N,N -Dimethylformamid

DMS Dimethyl sulﬁde

DMSO Dimethyl sulfoxide

E1/2 Half wave potential

EA Elemental Analysis

EGDMA Ethylene glycol dimethacrylate

ESI Electrospray ionization

FAB Fast atom bombardment

Fc Ferrocene/ferrocenyl-

ﬁg. Figure

Hbdmvpza Bis(3,5-dimethyl-4-vinylpyrazol-1-yl)acidic acid

HOPhbdmeTMSpzm (2-Hydroxyphenyl)-bis(3,5-dimethyl-4-(trimethylsilyl)ethynylpyrazol-1-yl)methane

Hz Hertz

ICP-AES Inductively coupled plasma atomic emission spectroscopy

IR Infrared spectroscopy

K[pz] Potassium 3,5-di-tert-butylpyrazolate m Multiplet

232 B Abbreviations m/z Ratio of mass to charge mbefcpzac Methyl bis(4-ethynylferrocenylpyrazol-1-yl)acetate mbepfcpzac Methyl bis((4-ethynyl-1-ferrocenylphen-4-yl)pyrazol-1-yl)- acetate

MMA Methyl methacrylate

Mo-co Molybdenum cofactor

MoCD Molybdenum cofactor deﬁciency

MOF Metal organic framework

MS Mass spectrometry

NBS N-bromosuccinimide

NMR Nuclear magnetic resonance

OAT Oxygen atom transfer

PEG Polyethylene glycol

PMMA Poly(methyl methacrylate) ppm Parts per million

Ptr Pterin pybut [1,4-Bis(4-pyridyl)butadiyne] pyphe [1,4-Bis(4-pyridylethynyl)phenylene] pz Pyrazolyl-

RT Room temperature

S Substrate s Singlet

SHE Standard hydrogen electrode

SO Sulﬁte oxidase t Triplet

233 Appendix

THF Tetrahydrofuran

TOF Turnover frequency

TON Turnover number

Trt Triphenylmethyl-/Trityl- y Yield

234 C List of Compounds

C List of Compounds

- Bis(3,5-dimethyl-4-formylpyrazol-1-yl)methane (1) - Bis(3,5-dimethyl-4-vinylpyrazol-1-yl)methane (bdmvpzm) (2)

- [MoO2Cl2(bdmvpzm)] (3) - Bis(3,5-dimethyl-4-vinylpyrazol-1-yl)acetic acid (Hbdmvpza) (4)

- [MoO2Cl(bdmvpza)] (5) - MMA copolymer of 2 (P6) - EGDMA copolymer of 2 (P7) - MMA copolymer of 4 (P8) - EGDMA copolymer of 4 (P9) - Molybdenum(VI) containing MMA copolymer (P6-Mo) - Molybdenum(VI) containing EGDMA copolymer (P7-Mo) - Molybdenum(VI) containing MMA copolymer (P8-Mo) - Molybdenum(VI) containing EGDMA copolymer (P9-Mo) - MMA copolymer of complex 3 (P10) - EGDMA copolymer of complex 3 (P11) - MMA copolymer of complex 5 (P12) - EGDMA copolymer of complex 5 (P13) - Bis(4-(2,2-dibromovinyl)-3,5-dimethylpyrazol-1-yl)methane (14) - Bis(4-ethynyl-3,5-dimethylpyrazol-1-yl)methane (bedmpzm) (15) - Bis(4-trimethylsilyl-ethynyl-3,5-dimethylpyrazol-1-yl)acetic acid (16) - [CuI(bedmpzm)] (17)

- [ZnCl2(bedmpzm)] (18)

- [MnCl2(bedmpzm)] (19)

- [CoCl2(bedmpzm)] (20)

- [MoO2Cl2(bedmpzm)] (21) - 4-Iodopyrazole (22) - 4-Iodo-3,5-dimethylpyrazole (23) - 4-Iodo-1-tritylpyrazol (24) - 4-Iodo-3,5-dimethyl-1-tritylpyrazole (25) - 3,5-Dimethyl-4-(trimethylsilyl)ethynyl-1-tritylpyrazole (26) - 4-(Trimethylsilyl)ethynyl-1-tritylpyrazole (27) - 3,5-Dimethyl-4-(trimethylsilyl)ethynylpyrazole (28)

235 Appendix

- 2,2-Bis(4-ethynyl-3,5-dimethylpyrazol-1-yl)acetic acid (29) - (2-Hydroxyphenyl)-bis(3,5-dimethyl-4-(trimethylsilyl)ethynylpyrazol-1-yl)methane [HOPhbdmeTMSpzm] (30) TMS - [MoO2Cl2(HOPhbdme pzm)] (31) - (2-Hydroxyphenyl)-bis(3,5-dimethyl-4-ethynylpyrazol-1-yl)methane (32) - (1-Methylimidazol-2-yl)-bis(3,5-dimethyl-4-(trimethylsilyl)ethynylpyrazol-1-yl)methane (33) - (1-Methylimidazol-2-yl)-bis(3,5-dimethyl-4-ethynylpyrazol-1-yl)methane (34) - 3,5-Dimethyl-4-ethynyl-1-tritylpyrazole (35) - 1,4-Bis(3,5-dimethyl-1-tritylpyrazole-4-yl)butadiyne (36) - 1,4-Bis(3,5-dimethyl-1H -pyrazol-4-yl)butadiyne (37) - Poly(cobalt(II)acetylacetonato-bis(1,4-bis(3,5-dimethylpyrazol-4-yl)butadiyne)) (38/39) - Poly(cobalt(II)chlorido-bis(1,4-bis(3,5-dimethyl-1H -pyrazol-4-yl)butadiyne)) (40) - Poly(cobalt(II)bromido-bis(1,4-bis(3,5-dimethyl-1H -pyrazol-4-yl)butadiyne)) (41) - 4-Ethynyl-1-tritylpyrazole (42) - 1,4-Bis(1-tritylpyrazol-4-yl)butadiyne (43) - 1,4-Bis(1H -pyrazol-4-yl)butadiyne (44) - Bis(4-iodo-3,5-dimethylpyrazol-1-yl)methane (45) - Bis(4-iodopyrazol-1-yl)methane (46) - Bis(4-iodopyrazol-1-yl)acetic acid (47) - Bis(4-iodo-3,5-dimethylpyrazol-1-yl)acetic acid (48) - Methyl bis(4-iodopyrazol-1-yl)acetate (49) - Methyl bis(4-iodopyrazol-1-yl)acetate (50) - Bis(4-ethynylferrocenylpyrazol-1-yl)methane (51) - Methyl bis(4-ethynylferrocenylpyrazol-1-yl)acetate (52) - Bis((4-ethynyl-(1-(ferrocenyl)-phen-4-yl))-3,5-dimethylpyrazol-1-yl)methane (53) - Methyl bis(4-ethynyl-(1-(ferrocenyl)-phen-4-yl)pyrazol-1-yl)acetate (54) - Bis(3,5-dimethyl-4-(1-ferrocenyl-1,2,3-triazol-4-yl)pyrazol-1-yl)methane (55) - Bis(3,5-dimethyl-4-(1-methylferrocenyl-1,2,3-triazol-4-yl)pyrazol-1-yl)methane (56)

236 Bibliography

[1] S. Troﬁmenko, J. Am. Chem. Soc. 1967, 89, 3904–3905.

[2] S. Troﬁmenko, Chem. Rev. 1993, 88, 943–980.

[3] A. Otero, J. Fernández-Baeza, A. Antiñolo, J. Tejeda, A. Lara-Sánchez, Dalton Trans. 2004, 1499–1510.

[4] P. Ghosh, G. Parkin, J. Chem. Soc. Dalton Trans. 1998, 2281–2283.

[5] M. Ruf, H. Vahrenkamp, Inorg. Chem. 1996, 35, 6571–6578.

[6] A. Antiñolo, F. Carrillo-Hermosilla, E. Díez-Barra, J. Fernández-Baeza, M. Fer- nández, A. Lara-Sánchez, A. Moreno, A. Otero, A. Maria Rodríguez, J. Tejeda, J. Chem. Soc. Dalton Trans. 1998, 3737–3744.

[7] J. Fernández-Baeza, F. A. Jálon, A. Otero, M. E. Rodrigo-Blanco, J. Chem. Soc. Dalton Trans. 1995, 1015–1021.

[8] W. Hückel, H. Bretschneider, Ber. Dtsch. Chem. Ges. 1937, 70, 2024–2026.

[9] A. Otero, J. Fernández-Baeza, J. Tejeda, A. Antiñolo, F. Carillo-Hermosilla, E. Díez-Barra, A. Lara-Sánchez, M. Fernández-López, M. Lanfranchi, M. A. Pellinghelli, J. Chem. Soc. Dalton Trans. 1999, 3537–3539.

[10] A. Otero, J. Fernández-Baeza, J. Tejeda, A. Antiñolo, F. Carrillo-Hermosilla, E. Díez-Barra, A. Lara-Sánchez, M. Fernández-López, J. Chem. Soc. Dalton Trans. 2000, 2367–2374.

[11] N. Burzlaﬀ, I. Hegelmann, B. Weibert, J. Organomet. Chem. 2001, 626, 16–23.

[12] A. Beck, B. Weibert, N. Burzlaﬀ, Eur. J. Inorg. Chem. 2001, 521–527.

[13] a) A. Beck, A. Barth, E. Hübner, N. Burzlaff, Inorg. Chem. 2003, 42, 7182–7188; b) N. Burzlaff, I. Hegelmann, Inorg. Chim. Acta 2002, 329, 147–150; c) A. López- Hernández, R. Müller, H. Kopf, N. Buzrlaff, Eur. J. Inorg. Chem. 2002, 671–677; d) I. Hegelmann, A. Beck, C. Eichhorn, B. Weibert, N. Buzrlaff, Eur. J. Inorg. Chem. 2003, 339–347.

[14] E. L. Hegg, L. Que Jr, Eur. J. Biochem. 1997, 250, 625–629.

237 Bibliography

[15] K. D. Koehntop, J. P. Emerson, L. Que Jr., J. Biol. Inorg. Chem. 2005, 10, 87–93.

[16] a) T. C. Higgs, C. J. Carrano, Inorg. Chem. 1997, 36, 298–306; b) T. C. Higgs, C. J. Carrano, Inorg. Chem. 1997, 36, 291–297; c) T. C. Higgs, D. Ji, R. S. Czer- nuscewicz, C. J. Carrano, Inorg. Chim. Acta 1998, 273, 14–23.

[17] T. C. Higgs, D. Ji, R. S. Czernuscewicz, B. F. Matzanke, V. Schunemann, A. X. Trautwein, M. Helliwell, W. Ramirez, C. J. Carrano, Inorg. Chem. 1998, 37, 2383– 2392.

[18] P. K. Byers, A. J. Canty, R. T. Honeyman, J. Organomet. Chem. 1990, 385, 417– 427.

[19] L. K. Peterson, E. Kiehlmann, A. R. Sanger, K. I. Thé, Can. J. Chem. 1974, 52, 2367–2374rr.

[20] K. I. Thé, L. K. Peterson, Can. J. Chem. 1973, 51, 422–426.

[21] K. I. Thé, L. K. Peterson, E. Kiehlmann, Can. J. Chem. 1973, 51, 2448–2451.

[22] E. Galardon, M. Giorgi, I. Artaud, Dalton Trans. 2007, 1047–1052.

[23] J. Elﬂein, F. Platzmann, N. Burzlaﬀ, Eur. J. Inorg. Chem. 2007, 5173–5176.

[24] D. L. Reger, T. C. Grattan, K. J. Brown, C. A. Little, J. J. S. Lamba, A. L. Rheingold, R. D. Sommer, J. Organomet. Chem. 2000, 607, 120–128.

[25] D. L. Reger, J. R. Gardinier, T. C. Grattan, M. D. Smith, J. Organomet. Chem. 2005, 690, 1901–1912.

[26] D. L. Reger, R. P. Watson, M. D. Smith, P. J. Pellechia, Organometallics 2005, 25, 743–755.

[27] J. Rebek, S. Wolf, A. Mossman, J. Org. Chem. 1978, 43, 180–181.

[28] a) D. D. LeCloux, C. J. Tokar, M. Osawa, R. P. Houser, M. C. Keyes, W. B. Tolman, Organometallics 1994, 13, 2855–2866; b) D. D. LeCloux, W. B. Tolman, J. Am. Chem. Soc. 1993, 115, 1153–1154; c) C. J. Tokar, P. B. Kettler, W. B. Tolman, Organometallics 1992, 11, 2737–2739.

[29] A. Otero, J. Fernánda-Baeza, A. Antiñolo, J. Tejeda, A. Lara-Sánchez, L. Sánchez- Barba, M. Sánchez-Molina, S. Franco, I. López-Solera, A. M. Rodríguez, Eur. J. Inorg. Chem. 2006, 707–710.

238 Bibliography

[30] a) T. Godau, S. M. Bleifuß, A. L. Müller, T. Roth, S. Hoffmann, F. W. Heinemann, N. Burzlaff, Dalton Trans. 2011, 40, 6547–6554; b) T. Godau, F. Platzmann, F. W. Heinemann, N. Burzlaff, Dalton Trans. 2009, 254–255; c) S. M. Bleifuß, F. H. F. Hofmann, N. Burzlaff, Z. Anorg. Allg. Chem. 2013, 639, 1433–1437.

[31] A. Hoﬀmann, U. Flörke, M. Schürmann, S. Herres-Pawlis, Eur. J. Org. Chem. 2010, 4136–4144.

[32] I. Hegelmann, A. Beck, C. Eichhorn, B. Weibert, N. Burzlaﬀ, Eur. J. Inorg. Chem. 2003, 339–347.

[33] E. Hübner, G. Türkoglu, M. Wolf, U. Zenneck, N. Burzlaﬀ, Eur. J. Inorg. Chem. 2008, 1226–1235.

[34] E. Hübner, T. Haas, N. Burzlaﬀ, Eur. J. Inorg. Chem. 2006, 4989–4997.

[35] G. Türkoglu, C. Pubill Ulldemolins, R. Müller, E. Hübner, F. W. Heinemann, M. Wolf, N. Burzlaﬀ, Eur. J. Inorg. Chem. 2010, 2962–2974.

[36] K. Severin, Curr. Opin. Chem. Biol. 2000, 4, 710–714.

[37] K. Polborn, K. Sever, Chem. Commun. 1999, 2481–2482.

[38] K. Polborn, K. Severin, Chem.-Eur. J. 2000, 6, 4604–4611.

[39] K. Polborn, K. Severin, Eur. J. Inorg. Chem. 2000, 1687–1692.

[40] E. Burri, M. Öhm, C. Daguenet, K. Severin, Chem.-Eur. J. 2005, 11, 5055–5061.

[41] A. Schiller, R. Scopelliti, K. Severin, Dalton Trans. 2006, 3858–3867.

[42] A. Schiller, R. Scopelliti, M. Benmelouka, K. Severin, Inorg. Chem. 2005, 44, 6482– 6492.

[43] S. Julià, P. Sala, J. Del Marzo, M. Sancho, J. Heterocycl. Chem. 1982, 19, 1141– 1145.

[44] A. S. Potapov, A. I. Khlebnikov, V. D. Ogorodnikov, Russ. J. Org. Chem. 2006, 42, 550–554.

[45] A. K. Ho, I. Iin, P. A. Gurr, M. F. Mills, G. G. Qiao, Polymer 2005, 46, 6727–6735.

[46] T. J. Kealy, P. L. Pauson, Nature 1951, 168, 1039–1040.

[47] a) G. Wilkinson, M. Rosenblum, M. C. Whiting, R. B. Woodward, J. Am. Chem. Soc. 1952, 74, 2125–2126; b) R. B. Woodward, M. Rosenblum, M. C. Whiting, J. Am. Chem. Soc. 1952, 74, 3458–3459.

239 Bibliography

[48] a) E. O. Fischer, W. Pfab, Z. Naturforsch. 1952, 7b, 377–9; b) J. D. Dunitz, L. E. Orgel, A. Rich, Acta Cryst. 1956, 9, 373–375.

[49] a) U. Siemeling, Z. Anorg. Allg. Chemie 2005, 631, 2957–2966; b) R. C. J. Atkinson, V. C. Gibson, N. J. Long, Chem. Soc. Rev. 2004, 33, 313–328.

[50] D. Kalita, M. Morisue, Y. Kobuke, New. J. Chem. 2006, 30, 77–92.

[51] O. Juergens, J. Vidal-Gancedo, C. Rovira, K. Wurst, C. Sporer, B. Bildstein, H. Schottenberger, P. Jaitner, J. Veciana, Inorg. Chem. 1998, 37, 4547–4558.

[52] J. L. Lopez, A. Tárraga, A. Espinosa, M. D. Velasco, P. Moline, V. Lloveras, J. Vidal-Gancedo, C. Rovira, J. Veciana, D. J. Evans, K. Wurst, Chem.–Eur. J. 2004, 10, 4547–4558.

[53] a) M. F. R. Fouda, M. M. Abd-Elzaher, R. A. Abdelsamaia, A. A. Labib, Appl. Organomet. Chem. 2007, 21, 613–625; b) A. Nguyen, A. Vessieres, E. A. Hillard, S. Top, P. Pigeon, G. Jaouen, Chimia 2007, 61, 716–724; c) C. Y. Acevedo- Morantes, E. Melendez, S. P. Singh, J. E. Ramirez-Vick, J. Cancer Sci. Ther. 2012, 4, 271–275.

[54] a) I. M. Lorkovic, R. R. Duﬀ, M. S. Wrighton, J. Am. Chem. Soc. 1995, 117, 3617– 3618; b) C. K. A. Gregson, V. C. Gibson, N. J. Long, E. L. Marshall, P. J. Oxford, A. J. P. White, J. Am. Chem. Soc. 2006, 128, 7410–7411.

[55] U. Siemeling in Ferrocenes, John Wiley & Sons, 2008, pp. 141–176.

[56] W. Siebert, W. Ruf, K.-J. Schaper, T. Renk, J. Organomet. Chem. 1977, 128, 219–224.

[57] R. W. Fish, M. Rosenblum, J. Org. Chem. 1965, 30, 1253–1254.

[58] a) D. Guillaneux, H. B. Kagan, J. Org. Chem. 1995, 60, 2502–2505; b) F. Rebiere, O. Samuel, H. B. Kagan, Tetrahedron Lett. 1990, 31, 3121–3124; c) R. Sanders, U. T. Mueller-Westerhoﬀ, J. Organomet. Chem. 1996, 512, 219–224.

[59] F. S. Kamounah, J. B. Christensen, J. Chem. Res. Synop. 1997, 150.

[60] R. C. J. Atkinson, N. J. Long in Ferrocenes, John Wiley & Sons, 2008, pp. 3–32.

[61] a) J. Rajput, J. R. Moss, A. T. Hutton, D. T. Hendricks, C. E. Arendse, C. Imrie, J. Organomet. Chem. 2004, 689, 1553–1568; b) J. Rajput, A. T. Hutton, J. R. Moss, H. Su, C. Imrie, J. Organomet. Chem. 2006, 691, 4573–4588.

[62] S. Özçubukçu, E. Schmitt, A. Leifert, C. Bolm, Synthesis 2007, 389–392.

240 Bibliography

[63] V. H. Purecha, N. S. Nandurkar, B. M. Bhanage, J. M. Nagarkar, Tetrahedron Lett. 2008, 49, 1384–1387.

[64] T. Mochida, K. Okazawa, R. Horikoshi, Dalton Trans. 2006, 693–704.

[65] a) O. N. Chupakhin, I. A. Utepova, I. S. Kovalev, V. L. Rusinov, Z. A. Starikova, Eur. J. Org. Chem. 2007, 857–862; b) C. Xu, Z.-Q. Wang, W.-J. Fu, X.-H. Lou, Y.-F. Li, F.-F. Cen, H.-J. Ma, B.-M. Ji, Organometallics 2009, 28, 1909–1916.

[66] R. Horikoshi, C. Nambu, T. Mochida, Inorg. Chem. 2003, 42, 6868–6875.

[67] F. Zapata, A. Caballero, A. Espinosa, A. Tárraga, P. Molina, J. Org. Chem. 2009, 74, 4787–4796.

[68] S. D. Köster, J. Dittrich, G. Gasser, N. Hüsken, I. C. Henao Castaneda, J. L. Jios, C. O. Della Védova, N. Metzler-Nolte, Organometallics 2008, 27, 6326–6332.

[69] T. S. Romero, A. Caballero, A. Tárraga, P. Molina, Org. Lett. 2009, 11, 3466–3469.

[70] K. Niedenzu, J. Serwatowski, S. Troﬁmenko, Inorg. Chem. 1991, 30, 524–527.

[71] S. Tampier, S. M. Bleifuß, M. M. Abd-Elzaher, J. Sutter, F. W. Heinemann, N. Bur- zlaﬀ, Organometallics 2013, 32, 5935–5945.

[72] K. Sonogashira, Y. Tohda, N. Hagihara, Tetrahedron Lett. 1975, 16, 4467–4470.

[73] J. C. Torres, R. A. Pilli, M. D. Vargas, F. A. Violante, S. J. Garden, A. C. Pinto, Tetrahedron 2002, 58, 4487–4492.

[74] a) I. R. Butler, C. Soucy-Breau, Can. J. Chem. 1991, 69, 1117–1123; b) M. Korb, U. Pfaﬀ, A. Hildebrandt, T. Rüﬀer, H. Lang, Eur. J. Inorg. Chem. 2014, 1051–1061.

[75] R. Misra, T. Jadhav, S. M. Mobin, Dalton Trans. 2014, 43, 2013–2022.

[76] N. G. Connelly, W. E. Geiger, Chem. Rev. 1996, 96, 877–910.

[77] T. Mochida, F. Shimizu, H. Shimizu, K. Okazawa, F. Sato, D. Kuwahara, J. Organomet. Chem. 2007, 692, 1834–1844.

[78] P. Debroy, S. Roy, Coord. Chem. Rev. 2007, 251, 203–221.

[79] C. Levanda, K. Bechgaard, D. O. Cowan, J. Org. Chem. 1976, 41, 2700–2704.

[80] K. Niedenzu, J. Serwatowski, S. Troﬁmenko, Inorg. Chem. 1991, 30, 524–527.

[81] S. Troﬁmenko, J. C. Calabrese, J. S. Thompson, Inorg. Chem. 1987, 26, 1507–1514.

241 Bibliography

[82] F. Jäkle, K. Polborn, M. Wagner, Chem. Ber. 1996, 129, 603–606.

[83] a) F. Fabrizi de Biani, F. Jäkle, M. Spiegler, M. Wagner, P. Zanello, Inorg. Chem. 1997, 36, 2103–2111; b) E. Herdtweck, F. Peters, W. Scherer, M. Wagner, Polyhe- dron 1998, 17, 1149–1157; c) S. Guo, F. Peters, F. Fabrizi de Biani, J. W. Bats, E. Herdtweck, P. Zanello, M. Wagner, Inorg. Chem. 2001, 40, 4928–4936.

[84] C. Chen, R. F. Jordan, Organometallics 2010, 29, 3679–3682.

[85] E. R. Sirianni, G. P. A. Yap, K. H. Theopold, Inorg. Chem. 2014, 53, 9424–30.

[86] A. J. Bard, L. R. Faulkner, Electrochemical Methods Fundamentals and Applications, John Wiley & Sons, Hoboken, NJ, 2nd ed., 2001.

[87] O. Hayaishi, M. Katagiri, S. Rothberg, J. Am. Chem. Soc. 1955, 77, 5450–5451.

[88] L. P. Wackett, L. D. Kwart, D. T. Gibson, Biochemistry 1988, 27, 1360–1367.

[89] L. P. Wackett, Enzyme Microb. Technol. 2002, 31, 577–587.

[90] D. H. Peterson, H. C. Murry, J. Am. Chem. Soc. 1952, 74, 1871–1872.

[91] B. M. Choudary, N. S. Chowdari, K. Jyothi, M. L. Kantam, J. Am. Chem. Soc. 2002, 124, 5341–5349.

[92] B. Kauppi, K. Lee, E. Carredano, R. E. Parales, D. T. Gibson, H. Eklund, S. Ra- maswamy, Structure 1998, 6, 571–586.

[93] M. D. Wolfe, J. D. Lipscomb, J. Biol. Chem. 2003, 278, 829–835.

[94] M. B. Neibergall, A. Stubna, Y. Mekmouche, E. Münck, J. D. Lipscomb, Biochem- istry 2007, 46, 8004–8016.

[95] H. Beinert, R. H. Holm, E. Munck, Science 1997, 277, 653–659.

[96] A. Karlsson, J. V. Parales, R. E. Parales, D. T. Gibson, H. Eklund, S. Ramaswamy, Science 2003, 299, 1039–1042.

[97] E. Brown, R. Friemann, A. Karlsson, J. Parales, M. J. Couture, L. Eltis, S. Ra- maswamy, J. Biol. Inorg. Chem. 2008, 13, 1301–1313.

[98] A. M. Kuznetsov, E. M. Zueva, A. N. Masliy, L. I. Krishtalik, Biochim. Biophys. Acta Bioenerg. 2010, 1797, 347–359.

[99] J. Ballmann, A. Albers, S. Demeshko, S. Dechert, E. Bill, E. Bothe, U. Ryde, F. Meyer, Angew. Chem. Int. Ed. 2008, 47, 9537–9541.

242 Bibliography

[100] J. Ballmann, S. Dechert, S. Demeshko, F. Meyer, Eur. J. Inorg. Chem. 2009, 3219– 3225.

[101] M. G. G. Fuchs, S. Dechert, S. Demeshko, U. Ryde, F. Meyer, Inorg. Chem. 2010, 49, 5853–5858.

[102] P. D. Oldenburg, A. A. Shteinman, L. Que Jr., J. Am. Chem. Soc. 2005, 127, 15672–15673.

[103] P. D. Oldenburg, C.-Y. Ke, A. A. Tipton, A. A. Shteinman, L. Que Jr., Angew. Chem. Int. Ed. 2006, 45, 7975–7978.

[104] J. B. Howard, D. C. Rees, Chem. Rev. 1996, 96, 2965–2982.

[105] B. K. Burgess, D. J. Lowe, Chem. Rev. 1996, 96, 2983–3012.

[106] R. Hille, Chem. Rev. 1996, 96, 2757–2816.

[107] R. Mayilmurugan, B. N. Harum, M. Volpe, A. F. Sax, M. Palaniandavar, N. C. Mösch-Zanetti, Chem. Eur. J. 2011, 17, 704–713.

[108] R. Hille, Biochim. Biophys. Acta Bioenerg. 1994, 1184, 143–169.

[109] C. Kisker, H. Schindelin, A. Pacheco, W. A. Wehbi, R. M. Garrett, K. V. Ra- jagopalan, J. H. Enemark, D. C. Ress, Cell 1997, 91, 973–983.

[110] C. Feng, G. Tollin, J. H. Enemark, Biochim. Biophys. Acta Proteins Proteomics 2007, 527–539.

[111] H. Schindelin, C. Kisker, K. V. Rajagopalan in Advances in Protein Chemistry, Vol. 58, Academic Press Inc., San Diego, 2001, pp. 47–94.

[112] K. V. Rajagopalan, J. L. Johnson in Wiley Encyclopedia of Molecular Medicine (Ed.: T. E. Creighton), Wiley, New York, 2002, pp. 3048–3051.

[113] A. B. Dublin, J. K. Hald, S. L. Wootton-Gorges, Am. J. Neuroradiol. 2003, 23, 484–485.

[114] J. Reiss, J. L. Johnson, Hum. Mutat. 2003, 21, 569–576.

[115] J. L. Johnson, M. Duran in The Metabolic and Molecular Bases of Inherited Disease, McGraw-Hill, New York, 8th ed., 2001, pp. 3163–3177.

[116] A. Matthies, K. V. Rajagopalan, R. R. Mendel, S. Leimkuhler, Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 5946–5951.

243 Bibliography

[117] G. Schwarz, J. A. Santamaria-Araujo, S. Wolf, H. J. Lee, I. M. Adham, H. J. Grone, H. Schwegler, J. O. Sass, T. Otte, P. Hanzelmann, R. R. Mendel, W. Engel, J. Reiss, Hum. Mol. Genet. 2004, 13, 1249–1255.

[118] A. Veldmann, J. A. Santamaria-Auraujo, S. Sollazzo, J. Pitt, R. Gianello, J. Yaplito- Lee, F. Wong, C. A. Ramsden, J. Reiss, I. Cook, J. Fairweather, G. Schwarz, Pedi- atrics 2010, 125, 1249–1254.

[119] H. J. Lee, A. I. M., G. Schwarz, Hum. Mol. Genet. 2002, 11, 3309–3317.

[120] M. J. Rudolph, J. L. Johnson, K. V. Rajagopalan, C. Kisker, Acta Crystallogr. Sect. D: Biol. Crystallogr. 2003, 59, 1183–1191.

[121] R. Hille, Essays Biochem. 1999, 34, 125–137.

[122] R. Hille, Biochim. Biophys. Acta Bioenerg. 1994, 1184, 125–137.

[123] M. S. Brody, R. Hille, Biochim. Biophys. Acta Prot. Struct. Mol. Enzymol. 1995, 1253, 133–135.

[124] M. S. Brody, R. Hille, Biochemistry 1999, 38, 6668–6677.

[125] J. P. Caradonna, P. R. Reddy, R. H. Holm, J. Am. Chem. Soc. 1988, 110, 2139– 2144.

[126] M. A. Pietsch, M. B. Hall, Inorg. Chem. 1996, 35, 1273–1278.

[127] J. M. Berg, R. H. Holm, J. Am. Chem. Soc. 1985, 107, 925–932.

[128] J. M. Berg, R. H. Holm, J. Am. Chem. Soc. 1985, 107, 917–925.

[129] K. Heinze, A. Fischer, Eur. J. Inorg. Chem. 2007, 1020–1026.

[130] K. Heinze, G. Marano, A. Fischer, J. Inorg. Biochem. 2008, 102, 1199–1211.

[131] C. G. Young in Biomimetic Oxidations Catalyzed by Transition Metals (Ed.: B. Me- unier), Imperial College Press, London, 2004, pp. 415–459.

[132] J. H. Enemark, C. G. Young, Adv. Inorg. Chem. 1993, 40, 1–88.

[133] J. H. Enemark, J. J. A. Cooney, J. J. Wang, R. H. Holm, Chem. Rev. 2004, 104, 1175–1200.

[134] R. H. Holm, Coord. Chem. Rev. 1990, 100, 183–221.

[135] R. Schwesinger, Nachr. Chem. Tech. Lab. 1990, 38, 1214–1226.

244 Bibliography

[136] K. Heinze, A. Fischer, Eur. J. Inorg. Chem. 2010, 1939–1947.

[137] J. Leppin, C. Förster, K. Heinze, Inorg. Chem. 2014, 53, 12416–12427.

[138] J. H. Weiner, R. A. Rothery, C. A. Sambasivarao, Trieber, Biochim. Biophys. Acta 1992, 1102, 1–18.

[139] T. Satoh, F. N. Kurihara, J. Biochem. 1987, 102, 191–197.

[140] A. G. McEwan, S. J. Ferguson, J. B. Jackson, J. Biochem. 1991, 274, 305–307.

[141] C. Kisker, H. Schindelin, D. Baas, J. Rétey, R. U. Meckenstock, P. M. H. Kroneck, FEMS Microbiol. Rev. 1999, 22, 503–521.

[142] F. Schneider, J. Löwe, R. Huber, H. Schindelin, C. Kisker, J. Knäblein, J. Mol. Biol. 1996, 263, 53–69.

[143] A. S. McAlpine, A. G. McEwan, A. L. Shaw, S. Bailey, J. Biol. Inorg. Chem. 1997, 2, 690–701.

[144] H. Schindelin, C. Kisker, J. Hilton, K. V. Rajagopalan, D. C. Rees, Science 1996, 272, 1615–1621.

[145] E. J. Enemark, J. J. A. Cooney in Concepts and Models in Bioinorganic Chemistry (Eds.: H.-B. Kraaty, N. Metzler-Nolte), Wiley-VCH, Weinheim, 2006, pp. 237–257.

[146] C. Kisker, H. Schindelin, D. C. Rees, Annu. Rev. Biochem. 1997, 66, 233–267.

[147] B. Fischer, H. Schmalle, E. Dubler, Inorg. Chem. 1995, 34, 5726–5734.

[148] K. Most, S. Köpke, F. Dall’Antionia, N. C. Mösch-Zanetti, Chem. Commun. 2002, 1676–1677.

[149] A. M. Santos, F. E. Kühn, K. Bruus-Jensen, I. Lucas, C. C. Romao, E. Herdtweck, J. Chem. Soc. Dalton Trans. 2001, 1332–1337.

[150] a) G. Lyashenko, G. Saischek, A. Pal, R. Herbst-Irmer, N. C. Mösch-Zanetti, Chem. Commun. 2007, 701–703; b) M. E. Judmaier, A. Wallner, G. N. Stipicic, K. Kirschner, J. Baumgartner, F. Belaj, N. C. Mösch-Zanetti, Inorg. Chem. 2009, 48, 10211–10221; c) G. Lyashenko, G. Saischek, M. E. Judmaier, M. Volpe, J. Baum- gartner, F. Belaj, V. Jancik, R. Herbst-Irmer, N. C. Mösch-Zanetti, Dalton Trans. 2009, 5655–5665; d) N. C. Mösch-Zanetti, D. Wurm, M. Volpe, G. Lyashenko, B. Harum, F. Belaj, J. Baumgartner, Inorg. Chem. 2010, 49, 8914–8921; e) T. Aru- muganathan, M. Volpe, B. Harum, D. Wurm, F. Belaj, N. C. Mösch-Zanetti, Inorg. Chem. 2011, 51, 150–156; f) T. Arumuganathan, R. Mayilmurugan, M. Volpe, N. C.

245 Bibliography

Mösch-Zanetti, Dalton Trans. 2011, 40, 7850–7857; g) M. Volpe, N. C. Mösch- Zanetti, Inorg. Chem. 2012, 51, 1440–1449.

[151] B. S. Hammes, B. S. Chohan, J. T. Hoﬀman, S. Einwächter, C. J. Carrano, Inorg. Chem. 2004, 43, 7800–7806.

[152] N. Kitanovski, B. Golobic, B. Ceh,˘ Inorg. Chem. 2006, 9, 296–299.

[153] A. Golobic, B. Ceh,˘ Acta Crystallogr. Sect. E: Struct. Rep. Online 2010, E66, m1648–m1649.

[154] N. Kitanovski, A. Golobi˘c,B. Ceh,˘ Inorg. Chem. Commun. 2011, 14, 276–280.

[155] A. Y. Robin, K. M. Fromm, Coord. Chem. Rev. 2006, 250, 2127–2157.

[156] J. Bailar, Coord. Chem. Rev. 1964, 83, 1–27.

[157] C. Janiak, Dalton Trans. 2003, 2781–2804.

[158] S. Kitagawa, S. Noro, ChemInform 2004, 35, 231.

[159] B. Moulton, M. J. Zaworotko, Chem. Rev. 2001, 101, 1629–1658.

[160] W. L. Leong, J. Chem. Rev. 2011, 111, 688–764.

[161] A. J. Blake, G. Baum, N. R. Champness, S. S. M. Chung, P. A. Cooke, D. Fenske, A. N. Khlobystov, D. A. Lemenovskii, W.-S. Li, M. Schroder, J. Chem. Soc. Dalton Trans. 2000, 4285–4291.

[162] Y. Hoshino, Y. Hagihara, Inorg. Chim. Acta 1999, 292, 64–72.

[163] M. Maekawa, K. Sugimoto, T. Kuroda-Sowa, Y. Suenaga, M. Munakata, J. Chem. Soc. Dalton Trans. 1999, 4357–4362.

[164] M. Maekawa, H. Konaka, Y. Suenaga, T. Kuroda-Sowa, M. Munakata, J. Chem. Soc. Dalton Trans. 2000, 4160–4166.

[165] M. B. Zaman, M. D. Smith, H.-C. zur Loye, Chem. Mater. 2001, 13, 3534–3541.

[166] M. B. Zaman, K. A. Udachin, J. A. Ripmeester, CrystEngComm 2002, 4, 613–617.

[167] M. Albrecht, M. Nieger, A. Schmidt, Z. Naturforsch. B: J. Chem. Sci. 2011, 66, 209–212.

[168] S. Han, Z. Ma, Y. Wei, V. C. Kravtsov, B. S. Luisi, I. Kulaots, B. Moulton, CrystEngComm 2011, 13, 4838–4840.

246 Bibliography

[169] C. Ding, X. Li, Y. Ding, X. Li, S. W. Ng, Y. Xie, Cryst. Growth Des. 2012, 12, 3465–3473.

[170] T. Waidmann, N. Fritsch, J. Tucher, M. Rudolf, F. Glaser, D. M. Guldi, N. Burzlaﬀ, CrystEngComm 2013, 15, 10157–10160.

[171] L. D. Ciana, A. Haim, J. Heterocycl. Chem. 1984, 21, 607–608.

[172] N. R. Champness, A. N. Khlobystov, A. G. Majuga, M. Schröder, N. V. Zyk, Tetrahedron Lett. 1999, 40, 5413–5416.

[173] J. Atienza, A. Gietiérrez, M. Felisa Perpinán, A. E. Sánchez, Eur. J. Inorg. Chem. 2008, 5524–5531.

[174] a) V. Colombo, S. Galli, H. J. Choi, G. D. Han, A. Maspero, G. Palmisano, N. Mas- ciocchi, J. R. Long, Chem. Sci. 2011, 2, 1311–1319; b) S. Galli, N. Masciocchi, V. Colombo, A. Maspero, G. Palmisano, F. J. López-Garzón, M. Domingo-Garcá, I. Fernández-Morales, E. Barea, J. A. R. Navarro, Chem. Mater. 2010, 22, 1664– 1672; c) N. Masciocchi, S. Galli, V. Colombo, A. Maspero, G. Palmisano, B. Seyyedi, C. Lamberti, S. Bordiga, J. Am. Chem. Soc. 2010, 132, 7902–7904; d) E. Quar- tapelle Procopio, F. A. T. Linares, C. Montoro, V. Colombo, A. Maspero, E. Barea, J. A. R. Navarro, Angew. Chem. Int. Ed. 2010, 49, 7308–7311.

[175] V. Colombo, C. Montoro, A. Maspero, G. Palmisano, N. Masciocchi, S. Galli, E. Barea, J. A. R. Navarro, J. Am. Chem. Soc. 2012, 134, 12830–12843.

[176] L.-Y. Du, W.-J. Shi, L. Hou, Y.-Y. Wang, Q.-Z. Shi, Z. Zhu, Inorg. Chem. 2013, 52, 14018–14027.

[177] C. Heering, I. Boldog, V. Vasylyeva, J. Sanchiz, C. Janiak, CrystEngComm 2013, 15, 9757–9768.

[178] S. Galli, A. Maspero, C. Giacobbe, G. Palmisano, L. Nardo, A. Comotti, I. Bas- sanetti, P. Sozzani, N. Masciocchi, J. Mater. Chem. 2014, 2, 12208–12221.

[179] A. Tăbăcaru, C. Pettinari, F. Marchetti, S. Galli, N. Masciocchi, Cryst. Growth Des. 2014, 14, 3142–3152.

[180] E. Q. Procopio, S. Rojas, N. M. Padial, S. Galli, N. Masciocchi, F. Linares, D. Miguel, J. E. Oltra, J. A. R. Navarro, E. Barea, Chem. Commun. 2011, 47, 11751–11753.

[181] E. Q. Procopio, N. M. Padial, N. Masciocchi, S. Galli, J. E. Oltra, E. Barea, J. A. R. Navarro, CrystEngComm 2013, 15, 9352–9355.

247 Bibliography

[182] N. M. Padial, E. Q. Procopio, C. Montoro, E. López, J. E. Oltra, V. Colombo, A. Maspero, N. Masciocchi, S. Galli, I. Senkovska, S. Kaskel, E. Barea, J. A. R. Navarro, Angew. Chem. Int. Ed. 2013, 52, 8290–8294.

[183] S. F. Vasilevsky, S. V. Klyatskaya, E. V. Tretyakov, J. Elguero, Heterocycles 2003, 60, 879–886.

[184] H. Friebolin, Basic one- and two-dimensonal NMR spectroscopy, Wiley-VCH, Wein- heim, 4th ed., 2005.

[185] a) K. Dreisch, C. Andersson, C. Stalhandske, Polyhedron 1993, 12, 303–311; b) B. Viossat, N. Rodier, Acta Cryst. 1979, B35, 2715–2718; c) D. M. Baird, F. L. Yang, D. J. Kavanaugh, Polyhedron 1996, 15, 2597–2606; d) V. S. Sergienko, V. L. Abramenko, M. A. Porai-Koshits, A. D. Garnovskii, Zh. Strukt. Khim. 1990, 31, 45–5; e) G. Minghetti, M. A. Cinellu, A. L. Bandini, A. L. Banditelli, F. Demartin, M. Manassero, J. Organomet. Chem. 1986, 315, 387–399; f) B. Bovio, A. Cingolani, F. Bonati, Z. Anorg. Allg. Chem. 1992, 610, 151–156; g) A. Lorenzotti, F. Bonati, A. Cingolani, G. G. Lobbia, D. Leonesi, B. Bovio, Inorg. Chim. Acta. 1990, 170, 199–208; h) M. R. Churchill, D. G. Churchill, M. H. Vo Huynh, K. J. Takeuchi, R. K. Castellano, D. L. Jameson, J. Chem. Cryst. 1996, 26, 179–183; i) B. Bovio, A. Cingolani, C. Pettinari, G. G. Lobbia, F. Bonati, Z. Anorg. Allg. Chem. 1991, 602, 169–177; j) C. Pettinari, A. Cingolani, Polyhedron 1996, 15, 115–126.

[186] G. Türkoglu, PhD thesis, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 2011.

[187] P. Nevest, S. Gago, S. S. Balula, A. D. Lopes, A. A. Valente, L. Cunha-Silva, F. A. A. Paz, M. Pillinger, J. Rocha, C. M. Silva, I. S. Gonçales, Inorg. Chem. 2011, 50, 3490–3500.

[188] H. Arzoumanian, R. Bakhtchadjian, Transition Met. Chem. 2006, 31, 681–689.

[189] R. Brückner, Reaktionsmechanismen, Spektrum Akademischer Verlag, München, 3rd ed., 2005, pp. 615–616.

[190] E. J. Corey, P. L. Fuchs, Tetrahedron Lett. 1972, 13, 3769–3772.

[191] C. Martín, M. Sierra, E. Alvarez, T. R. Belderrain, P. J. Pérez, Dalton Trans. 2012, 41, 5319–5325.

[192] M. A. I. Rodiíguez-Franco, I. Dorronsoro, A. I. Hernández-Higueras, G. Antequera, Tetrahedron Lett. 2001, 42, 863–865.

248 Bibliography

[193] G. Heinisch, W. Holzer, C. Obala, Monatsh. Chem. 1988, 119, 253–262.

[194] a) A. Baldy, J. Elguero, R. Faure, M. Pierrot, E. J. Vincent, J. Am. Chem. Soc. 1985, 107, 5290; b) J. A. S. Smith, B. Wehrle, F. Aguilar-Parrilla, H.-H. Limbach, C. Foces-Foces, F. H. Cano, J. Elguero, A. Baldy, M. Pierrot, M. M. T. Khursid, J. B. Larcombe-McDouall, J. Am. Chem. Soc. 1989, 111, 7304; c) F. Aguilar- Parrilla, G. Scherer, H.-H. Limbach, C. Foces-Foces, F. H. Cano, J. A. S. Smith, C. Toiron, J. Elguero, J. Am. Chem. Soc. 1992, 114, 9657; d) F. Aguilar-Parrilla, C. Cativiela, M. D. Díaz de Villegas, J. Elguero, C. Foces-Foces, J. I. García, F. H. Cano, H.-H. Limbach, J. A. S. Smith, C. Toiron, J. Chem. Soc. Perkin Trans. 2 1992, 1737; e) J. Elguero, F. H. Cano, C. Foces-Foces, A. L. Llamas-Saiz, H.-H. Limbach, F. Aguilar-Parrilla, R. M. Claramunt, C. López, J. Heterocycl. Chem. 1994, 31, 695.

[195] S. Bleifuß, PhD thesis, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 2014.

[196] G. L. Larson in The Chemistry of Organic Silicon Compounds, John Wiley & Sons, 1989, pp. 763–808.

[197] V. B. Damodaran, C. J. Fee, Eur. Pharma. Rev. 2010, 15, 18–26.

[198] a) C. Glaser, Liebigs Ann. Chem. 1870, 154, 137–171; b) C. Glaser, Ber. Dtsch. Chem. Ges. 1869, 2, 422–424.

[199] G. Eglinton, A. R. Galbraith, J. Chem. Soc. 1959, 889–893.

[200] M. A. Fox, J. K. Whitesell, Organic Chemistry, Jones & Bartlett Publishers, 3rd ed., 2004.

[201] G. A. Jeﬀrey, An Introduction to Hydrogen Bonding, Oxford University Press, 1997.

[202] a) N. Masciocchi, G. A. Ardizzoia, S. Brenna, G. LaMonica, A. Maspero, S. Galli, A. Sironi, Inorg. Chem. 2002, 41, 6080–6089; b) K. S. Chong, S. J. Rettig, A. Storr, J. Trotter, Can. J. Chem. 1979, 57, 3119–3125; c) E. V. Mutseneck, S. Bieller, M. Bolte, H.-W. Lerner, M. Wagner, Inorg. Chem. 2010, 49, 3540–3552.

[203] B. Bildstein, M. Schweiger, H. Angleitner, H. Kopacka, K. Wurst, K.-H. Ongania, M. Fontani, P. Zanello, Organometallics 1999, 18, 4286–4295.

[204] J. A. Januszewski, D. Wendinger, C. D. Methfessel, F. Hampel, R. R. Tykwinksi, Angew. Chem. Int. Ed. 2013, 52, 1817–1821.

[205] V. Cadierno, J. Gimeno, Chem. Rev. 2009, 109, 3512–3560.

249 Bibliography

[206] T. Mochida, H. Shimizu, S. Suzuki, T. Akasaka, J. Organomet. Chem. 2006, 691, 4882–4889.

[207] A. S. Potapov, A. I. Khlebnikov, S. F. Vasilevskii, Russ. J. Org. Chem. 2006, 42, 1368–1373.

[208] T. Jadhav, R. Maragani, R. Misra, V. Sreeramulu, D. N. Rao, S. M. Mobin, Dalton Trans. 2013, 42, 4340–4342.

[209] R. Misra, T. Jadhav, S. M. Mobin, Dalton Trans. 2013, 43, 2013–2022.

[210] H. Schottenberger, J. Lukassser, E. Reichel, A. G. Müller, G. Steiner, H. Kopacka, K. Wurst, K. H. Ongania, K. Kirchner, J. Organomet. Chem. 2001, 637, 558–576.

[211] D. Plazuk, B. Rychlik, A. Blauz, S. Domagala, J. Organomet. Chem. 2012, 715, 102–112.

[212] J. C. Barborak, J. M. Chance, J. Org. Chem. 1984, 49, 703–704.

[213] I. Choi, Y.-K. Kim, D.-H. Min, S. W. Lee, W.-S. Yeo, J. Am. Chem. Soc. 2011, 133, 16718–16721.

[214] G. Gritzner, J. Kuta, Pure Appl. Chem. 1984, 56, 461–466.

[215] G. M. Sheldrick, Acta Crystallogr. Sect. A 2008, 64, 112–122.

250 Danksagung

251 Danksagung

Mein besonderer Dank gilt meinem Doktorvater Prof. Dr. Nicolai Burzlaff für die Aufnahme in seine Arbeitsgruppe, den großen akademischen Freiraum zur Bearbeitung der interessanten Themenstellung, seine Unterstützung während der Promotion und die angenehme Atmosphäre im Arbeitskreis sowie für die Empfehlung für die Graduate School Molecular Science.

Bei Prof. Dr. Dr. hc. mult. Rudi van Eldik und seiner Arbeitsgruppe möchte ich mich für den freundlichen Empfang am Lehrstuhl und die stetige Versorgung mit Kaﬀee bedanken. Ebenso danke ich Herrn Prof. Dr. Sjoerd Harder dafür, dass sich das positive Arbeitsklima auch nach seiner Übernahme des Lehrstuhls nicht verändert hat.

Natürlich wäre so eine Arbeit nicht ohne die Mithilfe einer Vielzahl von Mitarbeitern des Departments möglich. Deshalb möchte ich mich bei Dr. Achim Zahl und Jochen Schmidt für die Messung unzähliger NMR-Spektren und bei Jochen zusätzlich für die Messung meiner AAS-Spektren bedanken. Für die Aufnahme der Massenspektren danke ich besonders Dr. Oliver Tröppner und dem Masse-Max Dürr. Außerdem danke ich Christina Wronna für die Durchführung der Elementaranalysen. Den Mitarbeitern der Werkstatt Peter Igel und Manfred Weller, dem Schreiner Wilfried Hof- mann und dem Elektriker Uwe Reißer danke ich für die Hilfe bei allerlei Problemen mit der Technik und dem Mobiliar sowie der häuﬁgen Unterstützung bei einer Vielzahl merkwürdiger Sonderanfertigungen für Promotionshüte. Natürlich möchte ich mich auch bei unserem Glasbläser Ronny Wiefel, bei Christl Hofmann für die Aufsicht über den Sondermüll sowie bei unseren Magazinmännern Roman Kania und Guido Grimm bedanken.

Mein besonderer Dank gilt den akademischen Räten Dr. Carlos Dücker-Benfer (einfach dafür, dass du bist wie du bist), Dr. Christian Färber (ich werde zeitlebens bei jeder größeren und kleineren Ansammlung von Kartons an dich denken) und Dr. Jörg Sutter (immer der rechte Spruch zur rechten Zeit). Bleibt wie ihr seid! Ohne euch würde so einiges fehlen. An dieser Stelle danke ich natürlich auch der heimlichen Cheﬁn des Lehrstuhls: Ursula Palmer. Danke, dass du dich so gewissenhaft um alles kümmerst und vor allem immer ein oﬀenes Ohr hast.

Meinen Kollegen aus dem Arbeitskreis gilt mein ganz besonderer Dank. Zum einen den Altvorderen Stefan Tampier, Gazi Türkoglu, Fatima Tepedino (alles für den Schäferhund), Tom Godau (auf dass wir bald auf dich anstoßen können), Andreas Beyer (der wohl größte Fugger am ganzen Ballermann) und natürlich Sascha Blei- fuß (was soll man da sagen... einfach für alles. Halt die Stellung an der Uni!). Natür- lich möchte ich mich auch ganz herzlich bei den nicht ganz so alten Kollegen bedanken.

252 Lieber Nico Fritsch (der König der Düse), lieber Philipp Rodehutskors (eines Tages komme ich mal vorbei auf der Hallig), lieber Frank Strinitz (bewahr dir deinen gesun- den Appetit), lieber Thomas Waidmann (danke für die gemeinsamen Jahre im Labor!), liebe Susy Spörler (danke für gelegentliche Blicke über den kulinarischen Tellerrand), liebe Eva Heinze (danke, dass du immer ein paar Kapazitäten für mich frei hattest) und liebe Julia Nils Stuber (ja, tief drinnen bist auch du ein Burzlaff), ich denke, man kann ohne Übertreibung sagen, ihr wart der beste Arbeitskreis, den man sich nur wünschen kann und ich hoffe, dass wir uns nicht so schnell aus den Augen verlieren werden. Danke für alles, ihr Zöpfe! Natürlich möchte ich mich auch bei allen neuen Burzlaffs bedanken: Marleen Mayer, Stephan Pflock und Lisa Müller, ich wünsche euch viel Glück und alles Gute für eure Promotion und ärgert die Susy nicht zu sehr!

Ebenso gilt mein Dank allen Mitarbeitern aus dem Arbeitskreis Harder. Insbesondere auch an Harmen Zijstra, Johanne Penafiel und Julia Intemann, ich hoﬀe, dass wir noch das ein oder andere Bier zusammen trinken werden. Darüber hinaus möchte ich mich bei meinen Mitarbeiter- und Bachelorstudenten danken, die mich im Laufe der Zeit unterstützt haben.

Zuletzt gilt jedoch mein größter Dank meinen Eltern, die mich während meiner Studienzeit stets unterstützt haben und immer für mich da waren und natürlich meiner Freundin Jani, ohne deren große Unterstützung und Verständnis in stressigen Phasen das alles nicht möglich gewesen wäre.

253