SYNTHESIS. PROPERTIES, AND APPLICATIONS

OF IONIC LIQUIDS

by

SERGEI V. DZYUBA. M.S.

A DISSERTATION

IN

CHEMISTRY

Submitted to the Graduate Faculty of Texas Tech University in Partial Fulfillment of the Requirements for the Degree of

DOCTOR OF PHILOSOPHY

Approved

Chairperson of the Committee

Accepted

Dean of the Graduate School

May, 2002 ACKNOWLEDGEMENTS

Looking at all the things I have had a chance to do thus far, I realize that many of those things (or maybe all of them) might never have happened if for not the people who have been involved in my life. I feel privileged to acknowledge these individuals for what I am and have right now.

Professor Richard A. Bartsch, my Ph.D. advisor, introduced me to the field of ionic liquids and made it a very challenging and enjoyable experience. I am in debt to him for his encouragement and guidance throughout my stay at Texas Tech University.

It has been an honor of being mentored by Professor Bartsch. Professors David M.

Bimey and Guigen Li, my Ph.D. committee members, have provided invaluable help in teaching and research. It has been a real pleasure of being taught and guided by them.

Due to the interdisciplinary nature of my dissertation research, I was very fortunate to learn from and collaborate with members of various research groups.

Professor Sindee L. Simon (Department of Chemical Engineering, TTU) was invaluable in introducing the principles of differential scanning calorimetry. I thank Professor

Dominick J. Casadonte, Jr. (Department of Chemistry and Biochemistry, TTU) for sharing the DSC equipment. I would like to thank Dr. Sangki Chun (Department of

Chemistry and Biochemistry, TTU) for performing extraction studies with ionic liquids.

I like to acknowledge Mr. David W. Purkiss (Department of Chemistry and

Biochemistry, TTU) for various 500 MHz NMR spectroscopy experiments. The contributions of Professor Edward L. Quitevis and Dr. Byung-Ryool Hyun (Department of Chemistry and Biochemistry, TTU) on intermolecular dynamics of ionic liquids are greatly acknowledged. Professor Robert W. Shaw and Ms. Shelly Wells (Department of

11 Chemistry and Biochemistry, TTU) are acknowledged for initiating the studies on ionic liquids as cryogenic solvents for biochemical processes. I want to thank Professor Robert

A. Flowers, II (Department of Chemistry and Biochemistry, TTU) for help with the set­ up of Karl-Fisher apparatus and for a generous gift of ethylammonium nitrate. Professor

Robin D. Rogers (Department of Chemistry, The University of Alabama) provided helpful suggestions in different aspects of ionic liquids.

I want to express my deepest and warmest gratitude to my parents. I feel enormously blessed having them at every step of my life, and knowing that I can always rely on their love, support and understanding.

HI TABLE OF CONTENTS

ACKNOWLEDGEMENTS ii

LIST OF TABLES xi

LIST OF FIGURES xvi

LIST OF SCHEMES xi

CHAPTER

I. ROOM-TEMPERATURE IONIC LIQUIDS - OLD NOVEL

SOLVENTS: AN INTRODUCTION 1

1.1. Nomenclature of Ionic Liquids 7

1.2. Present Status of the Field of Ionic Liquids II

1.3. Statement of Research Objectives 13

1.4. References 14

II. SYNTHESIS OF IONIC LIQUIDS 17 2.1. Preparation of l-Alkyl(aralkyl)-3-alkyr-imidazoIium / J Halides 17

2.2. Preparation of N-alkyl(aralkyl)pyridinium and-quinolinium -y Halides 26

2.3. Synthetic Routes to C2v-symmetric 1,3-Dialkylimidazolium / '.^ Salts 28

2.4. Introducing Functional Groups into Imidazolium Ionic Liquids 30

2.5. Synthesis of Dicationic Salts 34

IV 2.6. Metathesis Reactions to Introduce Other Anions into Ionic

Liquids 36

2.7. Preparation of Deuterated Ionic Liquids 38

2.8. Conclusions 41

2.9. Experimental Section 41

2.9.1. Materials 41

2.9.2. Physical and Analytical Methods 42

2.9.3. Synthesis of I-Alkyl(aralkyl)-3-methylimidazoIium Halides 1-10 42 2.9.4. Procedure for the Synthesis of 1-Substituted Imidazoles 14-20 42

2.9.5. Synthesis of l-Alkyl-3-alkyr-imidazolium and l-Aralkyl-3- alkyliimidazolium HaHdes 21-47 44

2.9.6. Synthesis of N-Alkyl(aralkyl)pyridinium Halides 51-54 50

2.9.7. Synthesis of N-Alkyl(aralkyl)quinolinium Bromides 55-56 50

2.9.8. Synthesis of Symmetric 1,3-Dialkylimidazolium Bromides 21 and 57-64 51

2.9.9. Synthesis of Ionic Liquids Containing Functional Groups

65-72 51

2.9.10. Synthesis of Symmetric Dicationic Ionic Liquids 73-75 53

2.9.11. Synthesis of Non-symmetric Dicationic Ionic Liquids 76-83 54 2.9.12. Synthesis of l-Alkyl-3-methylimidazolium Hexafluorophosphate [C„-mim]PF6 Room-Temperature Ionic Liquids 84-89 56 2.9.13. Synthesis of Deuterated Pyridine-Containing Room- Temperature Ionic Liquids 90 and 91 57

2.9.14. References 57

III. FINE-TUNING THE PHYSICAL PROPERTIES OF IONIC LIQUIDS 60

3.1. Phase Transition Temperatures of Ionic Liquids 63

3.1.1. Phase Transition Temperatures of l-Alkyl-3- methylimidazolium Hexafluorophosphate and Bis(trifluoromethyIsulfonyl)imide Ionic Liquids 64

3.1.2. Phase Transition Temperatures of l-Alkyl-3-alkyl'- imidazolium hexafluorophasphates 66

3.1.3. Phase Transition Temperatures of Symmetric 1,3-Dialkylimidazolium Hexafluorophasphate Ionic Liquids.... 70

3.1.4. Phase Transition Temperatures of l-Aralkyl-3- methylimidazolium Hexafluorophosphate and Bis(trifluoromethylsulfonyl)imide Ionic Liquids 72

3.2. Densities of Room-Temperature Ionic Liquids 74

3.2.1. Density of l-Substituted-3-methylimidazolium Room- Temperature Ionic Liquids 75

3.2.2. Influence of Temperature on the Density of Selected Ionic Liquids 77

3.3. Viscosities of Room-Temperature Ionic Liquids 78

3.3.1. Influence of Structure of l-AlkyI(aralkyl)-3- methylimidazolium Ionic Liquids on Dynamic Viscosity 79

3.3.2. Viscosity - Temperature Dependence for Room-Temperature Various Ionic Liquids 81

VI 3.4. Surface Tensions of Room-Temperature Ionic Liquids 83

3.5. Polarity of Room-Temperature Ionic Liquids 86

3.6. Conclusions 90

3.7. Experimental Section 93

3.7.1. Materials 93

3.7.2. Physical and Analytical Methods 93

3.7.3. Preparation of l-Alkyl-3-methylimidazolium Hexafluorophosphate and Bis(trifluoromethylsulfonyl)imide Ionic Liquids 94

3.7.4. Preparation of l-Aralkyl-3-methylimidazolium Hexafluorophosphate and Bis(trifluoromethyIsulfonyl)imide Ionic Liquids 95

3.7.5. Preparation of l-Alkyl-3-alkyl'-imidazolium Hexafluorophosphate Ionic Liquids 95

3.7.6. Preparation of Symmetric 1,3-DialkyHmidazoIium Hexafluorophosphate Ionic Liquids 102

3.7.7. Preparation of Ionic Liquids 155 - 157 Containing Functional Groups 102

3.8. References 103

IV. SPECTROSCOPIC STUDIES ON IONIC LIQUIDS 105

4.1. Nuclear Magnetic Resonance (NMR) Spectroscopy of Ionic Liquids.. 105

4.1.1. Influence of the Nature of Deuterated Molecular Solvents on the Chemical Shifts of Imidazolium-Containing Ionic Liquids. 106

4.1.2. Relative Assignment of the H(4)- and H(5)-Imidazolium Protons 107

Vll 4.1.2.1. Influence of the Nature of Deuterated Solvent 108

4.1.2.2. Influence of Concentration on the Relative Positions of the H(4)- and H(5)-Imidazolium Protons 108

4.1.2.3. Influence of Temperature on the Relative Positions of the H(4)- and H(5)-Imidazolium Protons 109

4.1.2.4. Influence of the Anion on the Relative Positions of the H(4)- and H(5)-Imidazolium Protons 109

4.1.2.5. Influence of the Imidazolium Cation Structure on the Relative Positions of the H(4)- and H(5)-Imidazolium Protons Ill

4.1.3. Influence of the Anion on the Chemical Shifts of the H(2)- Imidazolium Protons 112

4.1.4. Influence of Concentration on the Chemical Shifts Imidazolium Protons in Different Ionic Liquids 113

4.1.5. Influence of Elongation of the Alkyl Substituent (C„) in [C8-C„im]PF6 with n = 1-4 (88,110,118,164) and [(C6H5)2CH-C„im]NTf2 with n = 1-4 (165-168) Ionic Liquids on Chemical Shifts of the H(2)-, H(4)- and H(5)-imidazolium Protons 116

4.1.6. Influence of Temperature on the Chemical Shifts of [C8-mim]PF6 (88) Ionic Liquid 118

4.1.7. Influence of Concentration and Solvent on Anions of Several Ionic Liquid 119

4.1.7.1. Influence of Concentration and Solvent on the 'H NMR Chemical Shifts of CHjCOj" in [Cg- mim]CH3C02 Ionic Liquid (159) 120

viu 4.1.7.2. Influence of Concentration and Solvent on the '^F NMR Chemical Shifts of-N(S02CF3)2 and CFjCOj" in [Cg-mimJNTfj (101) and [C8-mim]CF3C02 (163)

Ionic Liquids 120

4.2. Intermolecular Dynamics of Room-Temperature Ionic Liquids 121

4.3. Conclusions 124

4.4. Experimental Section 125

4.4.1. Materials 125

4.4.2. Physical and Analytical Methods 125

44.3. Preparation of [C8-mim]B(C6H5)4 (160) and [C8-mim]BF4 (161) Ionic Liquids 126 4.4.4. Preparation of [C8-mim]CH3C02 (159), [C8-mim]N03 (162) and [Cg-mim]CF3C02 (163) Ionic Liquids 127

4.4.5. Preparation of l-Benzhydryl-3-alkylimidazolium Bis(trifluoromethylsulfonyl)imide Ionic Liquids 128

4.5. References 129

V. APPLICATIONS OF ROOM-TEMPERATURE IONIC LIQUIDS: EN ROUTE TO DESIGNER SOLVENTS 131

5.1. Application of Room-Temperature Ionic Liquids in Competitive Alkali Metal Salts Extraction by a Crown Ether 131

5.2. Ionic Liquids as Solvents for Enzymatic Reactions: Enzyme- Catalyzed, Lactam-Ring Opening Reactions in Ionic Liquids 134

5.3. Diels-Alder Reactions in Ionic Liquids 139

5.4. Conclusions 143

5.5. Experimental Section 144

IX 5.5.1. Materials 144

5.5.2. Competitive Solvent Extraction of Alkali Metal Salts from Aqueous Solution into Ionic Liquids and Molecular Organic Solvents 145

5.5.3. Determination of Enzyme Activity in Ionic Liquids 145

5.5.4. Representative Procedure for the Diels-Alder Reaction in Ionic Liquids 145

5.6. References 145 LIST OF TABLES

1.1 Melting points in °C of alkali metal halides and their crystal ionic

radii (in parentheses) in A 1

1.2 Melting points of some binary and tertiary inorganic salts mixtures... 3

1.3 Acute oral toxicity of ionic and molecular solvents in rats 13 2.1 Structures and yields of the l-alkyl-3-methylimidazolim bromides, [C„-mim]Br 19

2.2 Structures and yields for l-aralkyl-3-methylimidazolium halides, [C6H5(CH2)„-mim]X with X = CI or Br and [(C6H5)2CH-mim]Cl 21

2.3 Structures, reaction times and yields of l-alkyl-3- methylimidazolium halides prepared under microwave irradiation and heating 22

2.4 Yields of 1-alkylimidazoles 25

2.5 Conditions for selected metathesis reactions 36

3.1 Phase transition temperatures of [Cn-mimlPFg ionic liquids 65

3.2 Phase transition temperatures of [C„-mim]NTf2 room-temperature ionic liquids 66

3.3 Phase transition temperatures of [Cn-Cjim] PF^ ionic liquids 67

3.4 Phase transition temperatures of [C„-C3im] PFg ionic liquids 68

3.5 Phase transition temperatures of [C„-isoC4im]PF6 ionic liquids 69

3.6 Phase transition temperatures of[Cn-isoCjimlPF^ ionic liquids 70

3.7 Phase transition temperatures of [(C„)2-im]PF5 ionic liquids 71

XI 3.8 Phase transition temperatures of [C6H5(CH2)n-mim]PF6 ionic liquids. 73

3.9 Phase transition temperatures of [C6H5(CH2)n-mim]NTf2 ionic liquids 73

3.10 Influence of the anion on the density of room-temperature ionic liquids at 25 "C 75

3.11 Density (d) of l-alkyl-3-methylimidazolium ionic liquids determined with an Anton-PAAR density measurement system 76

3.12 Densities of [Ph(CH2)„-mim]NTf2 ionic liquids 77

3.13 Temperature dependence of density for several ionic liquids 78

3.14 Viscosities of [C„-mim]NTf2 ionic liquids at 25 °C 80

3.15 Viscosities of [C„-mim]PF6 ionic liquids at 25 °C 80

3.16 Temperature dependence of viscosity for several ionic liquids 82

3.17 Surface tensions of [C„-mim]NTf2 ionic liquids at 25 °C 84

3.18 Surface tensions of [C„-mim]PF6 ionic liquids at 25 °C 85

3.19 Surface tensions of [C6H5(CH2)„-mim]NTf2 ionic liquids at 25 °C .... 85

3.20 Polarities of ionic liquids 88

3.21 Chemical shifts of the imidazolium protons (III) with 10% of Reichardt's dye (IV) added and pure ionic liquid (in parentheses) as 0.1 M solutions in ^g-acetone and selected Reichardt's dye protons for O.IM solutions in rfg-acetone 90

4.1 Influence of the deuterated solvents on the chemical shifts in ppm of the H(4)- and H(5)-imidazolium protons of [Cg-mimlPFg (88) ionic liquid 108

4.2 Anion influence on the chemical shifts in ppm of imidazolium protons of [Cg-mimJX ionic liquids as 0.50 M solutions in CDCI3 110

xu 4.3 Chemical shifts in ppm for H(2)-imidazolium proton of [Cg-mim]X ionic liquids as 0.10 M solutions in CDCI3 at 25 °C 112

4.4 Dependence of chemical shifts in ppm for H(2)-imidazolium proton on concentration of [Cg-mimJX ionic liquids as solutions in CDCI3 at 25 °C 114

4.5 Dependence of chemical shifts in ppm for H(4)-imidazolium proton on concentration of [Cg-mim]X ionic liquids as solutions in CDCI3 at 25 "C 115

4.6 Alkyl group influence on the 'H NMR chemical shifts (in ppm) of H(2)-protons of [Cg-CnimJPFg ionic liquid as 0.10 M solutions in CDCI3 116

4.7 Chemical shifts (in ppm) of the H(2)-proton as a function of the alkyl group in [(C6H5)2CH-C„im]NTf2 ionic liquids as determined by 'H NMR spectroscopy at 0.10 M solutions in CDCI3 117

4.8 Chemical shifts of the H(2)-, H(4)- and H(5)-imidazolium protons in [C8-mim]PF6 (88) ionic liquid as a function of temperature at -25 °C / 25 °C / 50 °C at 2 and 0.05 M concentrations (in parentheses) as determined by 'H NMR spectroscopy 118

4.9 Influence of concentration and solvent on the chemical shifts (in ppm) of CH3C02~ in [C8-mim]CH3C02 ionic liquid (159) as determined by 'H NMR spectroscopy 120

4.10 Influence of solvent and concentration on the fluorine chemical shifts (in ppm) of [C8-mim]N(S02CF3)2 and [C8-mim]CF3C02 ionic liquid as determined by ''F NMR spectroscopy 121

5.1 Endo/exo selectivity of the Diels-Alder reaction and its correlation with polarity of the ionic liquids 143

Xlll LIST OF FIGURES

1.1 Examples of the first liquid organic salts 2

1.2 Phase diagram of l-ethyl-3-methylimidazolium chloroaluminate ionic liquid 4

1.3 Phase transition temperature (melting points (•), and glass (n), and clearing (•) transitions) diagram for l-alkyl-3-methylimidazolium tetrafluoroborate ionic liquids 7

1.4 Abbreviations for l-butyl-3-methylimidazolium hexafluorophosphate 8

1.5 Examples of abbreviations for different types of 1,3-disubstituted imidazolium bromides 9

1.6 Abbreviation for 1,2,3-trisubstituted imidazolium-based ionic liquids 10

1.7 Representative structures and abbreviations for N-substituted pyridinium and quinolinium bromides 10

2.1 Stmctures of l-alkyl(aralkyl)-3-alkylimidazolium halides 26

2.2 Synthesized N-alkyl(aralkyl)pyridinium halides 27

2.3 Synthesized N-alkyl(aralkyl)quinolinium bromides 28

2.4 "Task-specific" ionic liquids 31

3.1 Dependence of surface tension of several ionic liquids as a function

of temperature 83

3.2 Structures of functionalized room-temperature ionic liquids 87

3.3 Structures of solvatochromic dyes, i.e., Reichardt's dye (I) and Nile Red (II), used in determining the polarity of ionic liquids 88

XIV 4.1 Assignment of imidazolium protons in an l-alkyl-3- methylimidazolium cation 105

4.2 Possible modes of anion - cation interaction in [C8-mim]CH3C02

(159) ionic liquid with correlations shown by arrows Ill

4.3 Possible resonance structures of [Cg-C„im]PF6 ionic liquids 117

44 Normalized OHD-RIKES signals of [C„-mim]NTf2 ionic liquids 123 5.1 Influence of the length of the alkyl group (n) on the efficiency of competitive alkali metal cation extraction from aqueous solutions by DC18C6 in [C„-mim]PF6 ionic liquids 133

5.2 Influence of the length of the alkyl group in the imidazolium cation on the KVCs* and K*/Rb* selectivities in competitive alkali metal extraction from aqueous solution from DC18C6 by [C„-mim]PF6

ionic liquids 134

5.3 Structure of nitrocefine 138

5.4 Enzyme activity in ionic liquid - water systems 139

XV LIST OF SCHEMES

1.1 Acid-base equilibrium in a haloaluminate ionic liquid 4

1.2 Applications of haloaluminate ionic liquids in organic synthesis 5

1.3 Anion metathesis reactions 6

1.4 Suggested abbreviation for 1,3-disubtituted imidazolium salts 9

2.1 Literature preparations of 1 -alkyl-3-methylimdazolium halides 18

2.2 Facile preparation of [C4-mim]Br (1) ionic liquid 18

2.3 Synthesis of [C6H5CH2-mim]Br (10) ionic hquid 20

2.4 Microwave-assisted synthesis of [C„-mim]X ionic liquids 21

2.5 Synthesis of [Cj-mimlBr (3) ionic liquid under ultrasound

irradiation 23

2.6 Examples of available synthesis for 1 -substituted imidazoles 23

2.7 Synthesis of 1-alkylimidazoles 24

2.8 Synthesis of [Cn,-C„im]Br ionic liquids 25

2.9 Synthesis of N-substituted pyridinium bromides 27 2.10 Facile preparation of symmetric imidazolium ionic liquid from N- TMS-imidazole 29

2.11 Developed synthetic route to C2-symmetric 1,3-dialkyliniidazolium ionic liquids from imidazole 30

2.12 Preparation of hydroxy- and methoxy-containing imidazolium halides 32

2.13 Synthesis of fluorine-containing imidazolium iodides 33

XVI 2.14 Preparation of various carboxyl-containing imidazolium bromides... 34

2.15 Synthesis of bis-imidazolium halides 35

2.16 Preparation of unsymmetrical dicationic [(CH3)3N(CH2)„+,-mim]2Br

and [(CH3)3N(CH2)„^,-Py]2Br ionic liquids 35

2.17 Preparation of metal-free, room-temperature ionic liquids 38

2.18 Synthetic route to deuterated imidazoles and imidazolium salts 39

2.19 Synthesis of a deuterated pyridinium ionic liquids 40

5.1 Reported examples of lipase - assisted organic transformations in

ionic liquids 135

5.2 Enzymatic kinetic resolution of secondary alcohols in ionic liquids... 136

5.3 Glucose acylation in ionic liquids and molecular organic solvents.... 137

5.4 Diels-Alder reaction of cyclopentadiene and methyl aery late 140

XVll CHAPTER I

ROOM-TEMPERATURE IONIC LIQUIDS - OLD

NOVEL SOLVENTS: AN INTRODUCTION

What are ionic liquids? Simply saying, any liquid that consists entirely of ions can be called an ionic liquid. Following the same reasoning, ionic liquids that are fluid­ like at or around room temperature can be called room-temperature ionic liquids.

Throughout this dissertation, the terms ionic liquid and room-temperature ionic liquid will be used interchangeably.

It is common knowledge that salts are high melting solids (see Table 1.1).' In their liquid state, usuaUy well above 500 °C, they are highly corrosive and toxic.

However, the ionic environments provided by these liquid salts, also known as molten salts, could provide unique media for organic reactions and for separation processes. The high temperatures that are required to bring the salts into a fluid-like state significantly limit their applications. Obviously, no synthetic transformations can be performed in such media.

Table 1.1. Meltir ig points in 'C of alkali metal halides and their crystal ionic radii (in parent leses) in A.' Li* (0.68) Na* (0.97) K*(1.33) Rb*(1.47) Cs*(1.67)

F(1.33) 845 993 856 795 703

CI-(1.81) 605 801 770 718 645

Br (1.96) 550 747 734 693 636

r (2.20) 449 661 681 647 626 Salts that would be liquids at and below ambient temperatures are very desirable and potentially important. It should be noted that, in general, an increase of the cation or anion size leads to a lowering of the melting point (see Table 1.1). Mainly, this phenomenon is governed by the efficiency of packing in the crystal lattice. This comes from mismatching in the sizes of the anion and cation (but this should not be taken as a sole explanation for this phenomenon). Therefore, one of the ways to lower the melting point of a salt is to change the anion-cation pair. A reasonable way to accomplish this is to keep on increasing the size of the positively charged part of the salt. Clearly, with the inorganic cations this cannot be done any further than the periodic table of the elements allows. Therefore, an organic cation should be introduced into the salt. An almost infinite variety of organic structures should provide an efficient substrate-pool to accomplish this goal.

As early as 1914, salts with melting points below room temperature were introduced in the form of ammonium salts (see Figure 1.1).^ Later, pyridinium analogues were also reported .^'' These ammonium and pyridinium ionic liquids seem to meet all of the desired criteria for suitable ionic media.

^NH3 NO3 J ^N^ NO3

Figure 1.1. Examples of the first liquid organic salts.

Another approach to lower the melting points of inorganic salts is to use binary and tertiary systems as shown in Table 1.2.^ The use of aluminium(III) chloride (m.p. 192 "C)' showed great promise. The melting point values drop significantly, but are still fairly high for these systems to be used conveniently as reaction media. Nevertheless, it illustrates a possibility of forming low melting systems, which consist exclusively of inorganic components.

Table 1.2. Melting points of some binary and tertiary inorganic salts mixtures.''^

System Mole % M.p.,°C

LiCl - CsCl 60 - 40 355

NaCl - KCl 50 - 50 658

LiCl - AICI3 50 - 50 144 NaCl-AlCl3 50-50 151

In the early 1950s, these two approaches were combined. This led to the introduction of so-called the haloaluminate based-ionic liquids.'' However, it was not until 1980s that these liquid salts received a second examination to produce markedly increased activity in the field.' N-Alkylpyridinium halides combined in different proportions with aluminum halides produced a series of ionic liquids, some of which with the fraction AICI3 (or AlBr3) around 66%, were liquids below room-temperature.* Simple adjustments of the ratios of organic and inorganic salts produce ionic liquids with variable levels of acidity, as shown in Scheme 1.1. + AICI3 + AICI3

N; N + J CI J AICI4" J AI2CI7 basic neutral acidic strongly coordinating weakly coordinating noncoordinating

Scheme 1.1. Acid-base equilibria in a haloaluminate ionic liquid.

Further improvements came from the use of 1,3-dialkylimidazolium cations instead of N-alkylpyridinium cations.*'^ It was postulated that the heterocyclic cation should be asymmetric for the salt to be a liquid at room temperature. An advantage of the imidazolium salts is that they can be more conveniently modified than their pyridinium analogs.

0 0,1 Oi 0.3 0* Oil DC 0 7 X(AICl3) Figure 1.2. Phase diagram of l-ethyl-3-methylimidazolium chloroaluminate ionic liquid.'

Although a number of other inorganic chlorides can be prepared in combination with imidazolium halides,* it is the haloaluminate ionic liquids that received the most attention and were applied in several areas of organic chemistry. Representative examples showing the versatility and uniqueness of this medium are shown in Scheme 1.2. Classic carbon-carbon bond-forming Friedel-Crafts' and Diels-Alder'" reactions have been successfully carried out in this medium (see Schemes 1.2a and 1.2b, respectively). The ionic liquid serves as both the solvent and catalyst for these types of reactions. The ionic environment stabilizes and favors ionic species. This explains the formation of isopropylbenzene as the major product in the Friedel-Crafts reaction

(Scheme 1.2a). The acidity of the medium plays a very important role in determining the endo/exo product ratio in the Diels-Alder reaction (Scheme 1.2b). Also, a very important and versatile reaction for the preparation of an array of biologically active products, the

Fisher indole synthesis," was effectively performed in an ionic liquid (see Scheme Ic).'^

-Br (excess) (a)

L®^N-^ AlCU (0.67) 67" 29 % o // // COOCH3 (b) COOCH3 <**^C00CH3 X % (AICI3) endo/exo

48 4.88 51 19

Ri R2 R = H, P-CH3 R^ (c) NHNHp N=/

AICI4 (0.67) 41 - 92 %

Scheme 1.2. Applications of haloaluminate ionic liquids in organic synthesis. However, the haloaluminate type of room-temperature ionic liquids has some disadvantages. Mainly, the extremely hygroscopic nature of these solvents requires the use of inert atmosphere at every stage of their preparation and utilization. Also, special precautions are needed to synthesize these salts in sufficiently high purity for subsequent application. From the environmental point of view, the haloaluminate ionic liquids present a significant problem.

These problems led to the development of new types of room-temperature ionic liquids in the early 1990s.'^ The main difference being the anion. Tetrafluoroborate, nitrate and acetate anions in combination with l-ethyl-3-methylimidazolium cation produced a series of novel ionic liquids via bench top metathesis reactions (Scheme 1.3).

Subsequently, a number of other anions were introduced affording an array of room- temperature ionic liquids, with hexafluorophosphate-based ionic liquids being the most widely used at the present time.

[©N-x " [©N^X —^ _ \ MeOH or MeOH-HsO ^^ \ I X- = NO3-, BF4- and CH3CO2"

Scheme 1.3. Anion metathesis reactions.

Structural variations in these novel systems influence a number of the physical properties. Both the cationic and the anionic constituents play important roles in the determining the characteristics of the ionic liquid. Hexafluorophosphate-containing ionic liquids are non-hygroscopic, water-immiscible solvents; whereas the corresponding nitrates are hygroscopic and can be mixed with water in any proportions. The physical state of these solvents can be controlled by fine-tuning the structure of the cation as shown in Figure 1.3."' The ability to tailor the properties of these ionic solvents continues to attract researchers to this field.

-100 0 4 8 12 16 Alkyl ch^n length (n)

Figure 1.3. Phase transition temperature (melting points (•), and glass (D)- and clearing (•) transitions) diagram for l-alkyl-3-methylimidazolium tetrafluoroborate ionic liquids.'"

The properties of these novel air- and water-stable room-temperature ionic liquids have produced a burst of the research activity in this field. A number of organic reactions have been performed in these water- and air-stable ionic liquids, including oxidation,'^ hydrogenation,'* and coupling reactions.'^

1.1 Nomenclature of Ionic Liquids

I With the growing number of reports on ionic liquids, a convenient nomenclature system is required. Although most of the ionic liquids can quite simply be identifying by naming the cationic and anionic constituents according to the lUPAC nomenclature, an abbreviation-type approach would be useful. 1 Unfortunately, at the present time, the abbreviations are inconsistent and quite often a full name is required to identify the abbreviation. The major complications come from cation, since several abbreviations have been introduced. As shown in Figure 1.4, l-butyl-3-methylimidazolium hexafluorophosphate has been given a number of abbreviations. For letter-type abbreviations, certain complications arise when other substituted imidazoles and alkyl or

^N^. +;.N-^ PF.

[bmimlPFe,,'*^ BMrPF,,'*" [BMIMlPFg,'''^ [BuMIm][PFJ,'''' [C4-mim][PF6]''^

Figure 1.4. Abbreviations for l-butyl-3-methylimidazolium hexafluorophosphate.

aralkyl groups are used. To identify ionic liquids derived from 1-ethylimidazole and 1- propylimidazole, eim and pim, respectively, have been utilized. Unfortunately, this is not universal and does not take into consideration the case when a branched substituent is part of the starting imidazole. Also, in case of l-pentylimidazole the abbreviation will be the same as that for 1-propyIimidazole. The most widely used abbreviation for l-butyl-3- methylimidazolium hexafluorophosphate is [C4-mim]PF6, where C4 stands for butyl and mim represents methylimidazole. This is quite a convenient way to name the ionic liquids and that has been used in a number of instanses. To extend this convenient method to distinguish among different types of ionic liquids, a general approach for naming a l-alkyl-3-alkyr-imidazolium bromides is suggested in Scheme 1.4. H2n+lCnx N-^

Cnim

Br" I@'^"^"^^2m+1

lCn,-Cnim]Br

Scheme 1.4. Suggested abbreviation for 1,3-disubstituted imidazoUum salts.

Ionic liquids derived from 1-methylimidazole are the most widely used systems.

Conventionally, this moiety in ionic liquids was abbreviated as mim. This abbreviation can be used instead of Ciim. Following the same principles, this approach can be used to abbreviate more complicated ionic liquids as shown in Figure 1.5, when aralkyl or branched substituents are used on the imidazolium cation. Symmetric imidazolium cations can be abbreviated similarly.

H2n+lCrT^ H2n+iCn>. N + ).N- Br" Br'

[C6H5(CH2)n-Cnim]Br [isoC4-Cninri]Br

H2n+lGn. H2n+lGnN -OH "^^N-CnHgn+l ^^N- Br Br' [(Cn)2-im]Br or [Cn-Cnim]Br [HO(CH2)2-Cnim]Br

Figure 1.5. Examples of abbreviations for different types of 1,3-disubstituted imidazolium bromides. There is a limited amount of work performed with ionic liquids that have a substituent in the 2-position on the imidazolium ring (see Figure 1.6).'"^ The common practice is to put the first letter of the susbstituent in front of the mim, when n=l. For example, when R and n are methyl groups, the abbreviation is mmim. Although only a few substituents were introduced into this position, one can expect future expansions.

R

3N-CmH2m.1 Br" [Cm-RCnim]Br

Figure 1.6. Abbreviation for 1,2,3-trisubstituted imidazolium-based ionic liquids.

For the N-alkylpyridinium- and N-aUcylquinolinium-types of ionic liquids, a similar approach can be employed (Figure 1.7). This is done by using Py and Qu to represent the heterocyclic moiety, as chosen by their fu-st letters, and C^ for the alkyl group.

QN + Br - ^^ N + Br CnH2n+l [Cn-Py]Br [Cn-Qu]Br

Br ^ ^ OH [CsHsCHs-PylBr [HO(CH2)2-Py]Br

Figure 1.7. Representative structures and abbreviations for N-substituted pyridinium and quinolinium bromides.

10 Although this type of nomenclature is not widely accepted, its simplicity and clarity makes it very convenient for use in this dissertation.

1.2. Present Status of the Field of Ionic Liquids

With the understanding of some basic principles of haloaluminate ionic liquids came a wave of exploratory work on applications of these solvents. A slightly reversed situation occurred with air- and water-stable ionic liquids. Following a burst of activity in the field of ionic liquids in the 1990s dealing with applications of ionic liquids primarily in organic chemistry, research began on the fundamentals of the structural features, which govern the physical properties of these unique solvents. This is because some of the structural understanding of these ionic liquids was taken from the early work on the haloaluminates. Non-haloaluminate containing ionic liquids are now the main systems used in this field, due to their non-toxicity and ability for bench top use.

With a better understanding of how the stmcture of ionic liquids influences their properties, it should be possible to rationally design a solvent for a particular application.

This is the opposite of the current situation in which solvents dictate the choice of applications. This assumption of the rationally designed solvent created a long speculated term of "designer solvents."^" This term, introduced by K. R. Seddon in 1998, became one of the most unique, attractive and desirable features of ionic liquids. Based on a nearly infinite number of combinations of anions and cations, millions of ionic liquids can be created with varying properties. In comparison, the stmctural and property variations within molecular solvents are very limited. J

11 - At present, almost every research group engaged in ionic liquid research tries to at least touch on both structure and applications of the solvents. However, only a very few of the ionic liquids are in frequent use. \

One of the physical properties of the ionic liquid is their negligible vapor pressure. This is another attractive feature of the ionic liquids, which makes them

"green" or "greener" alternatives to conventional volatile organic solvents. Furthermore, in a number of applications ionic liquids were shown to be very effective recyclable and reusable media.^' Arguably the best selling point for promoting ionic liquids, the "green" solvent-approach has obvious drawbacks. Firstly, conventional solvents are still required to obtain ionic liquids in the high purity that is necessary for many applications. Also, molecular organic solvents are used to extract reaction products from the ionic liquids in work-up. Although alternative methods, primarily the use of supercritical CO2, are available,^^ their application is far from convenient and practical, since special equipment is required. Secondly, studies on the biological activity of these solvents are needed to support the claim that they are environmentally benign. To date, there is only one published study that addresses the issue of toxicity of ionic liquids.j The LD50 of 1- hexyloxymethyl-3-methylimidazolium tetrafluoroborate was tested using the Gaddum method on the Wistar rats (see Table 1.3)^^ Based on these numbers the ionic liquid was claimed to be non-toxic., However, this should not imply that all ionic liquids are as non­ toxic as this one. Clearly, more work is needed in this area before more convincing conclusions can be drawn.

12 Table 1.3. Acute oral toxicity of ionic and molecular solvents in rats.

Solvent LD50, mg/kg

[C,H,30CH2-mim]BF4 1370-1400

Acetone^ 5800

DMSO" 17500

Dichloromethane" 2136

" Reference 24.

Surely, the successful applications, primarily the "designer" solvent approach, will stimulate other areas of research on the ionic liquids. The versatility of these unique solvents also benefits other areas of chemical research. Among the latest successes, ionic liquids were used in recovery of biofuels^' and in deep desulfurization of diesel fuel.^*

The utilization of room-temperature ionic liquids as versatile lubricants was also described.^'

In spite of all the recent advances in the field of ionic liquids, there are many gaps to be filled. Main obstacles are the lack of comprehensive knowledge about the nature of the ionic liquids and the factors that govern their physical properties. Partially, this can be attributed to the limited number of ionic liquids that have been used thus far.

Furthermore, there are very few convenient synthetic routes to these solvents.

Collectively, this retards the realization of the "designer" solvent ability for ionic liquids.

1.3. Statement of Research Objectives

The major research objectives for this dissertation are:

1. Development of convenient procedures for the synthesis of ionic liquids;

13 2. Investigation of the basic physical properties of a variety ionic liquids to obtain insight onto the structure-property relationships; and

3. Exploration for a range of applications of room-temperature ionic liquids.

1.4. References

I. CRC Handbook of Chemistry and Physics, Boca Raton, Florida: CRC Press Inc., 65"" Edition, Ed. R. C. West, 1985.

I c 2. (a) P. Walden, Bull. Acad. Imper. Sci. (St. Petersburg) 1914, 1800; (b) E. S. Lane, J. Chem.Soc. 1953, 1172.

; 3. P. W. Atkins, Physical Chemistry, New York: W. H. Freeman and Co., 6'" Ed. 1998.

' 4. F. H. Hurley, T. P. Wier, J. Electrochem. Soc. 1951,98, 203.

U 5. J. S. Wilkes, J. A. Levisky, R. A. Wilson, C. L. Hussey, Inorg. Chem. 1982,21,1263.

6. C. L. Hussey, Arfv. Molten Salt Chem. 1983,5,185.

^ 1. K. R. Seddon, J. Chem. Tech. Biotechnol. 1997, 68, 351.

7 8. For some recent examples see: (a) E. R. Schreiter, J. E. Stevens, M. F. Ortwerth, R. G. Freeman, Inorg. Chem. 1999,38, 3935; (b) M. Hasan, I. V. Kozhevnikov, M. R. H. Siddiqui, C. Femoni, A. Steiner, N. Winterton, Inorg. Chem. 2001,40,795; (c) M. S. Sitze, E. R. Schreiter, E. V. Patterson, Inorg. Chem. 2001,40, 2298.

9. J. A. Boon, J. A. Levisky, J. L. Pflug, J. S. Wilkes, J. Org. Chem. 1986,56,480. For recent examples of other Friedel-Crafts reactions see: C. J. Adams, M. J. Earle, G. Roberts, K. R. Seddon, Chem. Commun. 1998,2097; A. Stark, B. L. MacLean, R. D. Singer, J. Chem. Soc, Dalton Trans. 1999, 63; S. J. Nara, J. R. Harjani, M. M. Salunkhe, J. Org. Chem. 2001,65, 8616.

10. W. Lee, Tetrahedron Lett. 1999,40,2461.

II. B. Robinson, Chem. Rev. 1963,63,373.

14 12. G. L. Rebeiro, B. M. Khadilkar, Synthesis 2001, 370.

^ 13. J. S. Wilkes, M. J. Zaworotko, J. Chem. Soc, Chem. Commun. 1992,965.

14. J. D. Holbrey, K. R. Seddon, J. Chem. Soc, Dalton Trans. 1999, 2133.

n 15.(a) G. S. Owens, M. M. Abu-Omar, Chem. Commun. 2000, 1165; (b) L. Gaillon, F. Bedioui, Chem. Commun. 2001, 1458; (c) O. Bortolini, V.Conte, C. Chiappe, G. Fantin, M. Fogagnolo, S. Maietti, Green Chem. 2002,4,94. fO 16. Y. Chauvin, L. Mussmann, H. Olivier, Angew. Chem. Int. Engl. 1995, 34, 2698. For an asymmetric version of hydrogenation reactions in ionic liquids see: R. A. Brown, P. Pollet, E. McKoon, C. A. Eckert, C. L. Liotta, P. G. Jessop, J. Am. Chem. Soc. 2001,123, 1254; S. Gemik, A. Wolfson, M. Herskowitz, N. Greenspoon, S. Geresh, Chem. Commun. 2001,2314.

[ I 17. (a) C. J. Mathews, P. J. Smith, T. Welton, Chem. Commun. 2000, 1249; (b) R. R. Deshmukh, R. Rajagopal, K. V. Srinivasan, Chem. Commun. 2001,1544.

7 18.(a) T. Itoh, E. Akasaki, K. Kudo, S. Shirakami, Chem. Lett. 2001, 262; (b) A. D. Headley, N. M. Jackson, J. Phys. Org. Chem. 2002, 75, 52; (c) S. H. Schofer, N. Kaftzik, P. Wasserscheid, U. Kragl, Chem. Commun. 2001,425; d) D. W. Armstrong, L. He, Y.-S. Liu, Anal. Chem. 1999, 77, 3873; (e) A. J. Carmichael, K. R. Seddon, J. Phys. Org. Chem. 2000,13,591.

[I 19. a) S. Dai, Y. H. Ju, C. E. Barnes, J. Chem. Soc. Dalton Trans. 1999, 1201; b) M. J. Muldoon, C. M. Gordon, I. R. Dunkin, J. Chem. Soc. Perkin Trans. 2 2001,433.

/ ^ 20. M. Freemantle, Chem. Eng. News 1998, 76 (March 30), 32.

21. For some of the recent examples see: (a) N. J. Rosa, C. A. M. Alfonso, A. G. Santos, Tetrahedron 2001,57, 4189; (b) H. Okazaki, Y. Kawanami, K. Yamamoto, Chem. Lett. 2001, 650; (c) C. E. Song, E. J. Roh, S. Lee, W. H. Shim, J. H. Choi, Chem. Commun. 2001,1122.

I C 22. (a) L. A. Blanchard, D. Hancu, E. J. Beckman, J. F. Brennecke, Nature 1999,399,28; (b) L. A. Blanchard, J. F. Brennecke, Ind. Eng. Chem. Res. 2001,40, 287; (c) F. Liu, M. B. Abrams, R. T. Baker, W. Tumas, Chem. Commun. 2001,433.

15 23. J. Pemak, A. Czepukowics, R. Pozniak, Ind. Eng. Chem. Res. 2001,40,2379.

24. Materials Safety Data Sheets, Mallinckrodt Baker, Inc.

1^ 25. A. G. Fadeev, M. M. Meager, Chem. Commun. 2001,295.

. 1 26. A. Bosmann, L. Datsevich, A. Jess, A. Lauter, C. Schmitz, P. Wasserscheid, Chem. ' ' Commun. 2001,2494.

I Y 27. C. Ye, W. Liu, Y. Chen, L. Yu, Chem. Commun. 2001,2244.

16 CHAPTER II

SYNTHESIS OF IONIC LIQUIDS

Diverse structural variations of the ionic liquids are necessary for comprehending the nature of these novel solvents. Preparations of 1,3-disubstituted imidazolium halide ionic liquids, which are described in literature, involve long reaction times and/or a large excess of one of the reactants. More importantiy, very limited structural variations of the cation seem to be due to a lack of convenient synthetic methods. The metathesis reaction to convert the halide-containing precursors to other ionic liquid needs improvements in terms of the process efficiency and the purity of the products. Altogether, this creates the necessity for a set of efficient synthetic procedures to assess the spectrum of anion and cation identities.

2.1. Preparation of l-Alkyl(aralkyl)-3-alklyl'-imidazolium Halides

The 1,3-disubstituted imidazolium halides have been prepared in straightforward fashion, as shown in Scheme 2.1.''^ Commercial availability of 1-methylimidazole contributes greatly to the fact that the majority of the ionic liquids incorporate this moiety in their stmctures. One of the main disadvantages for these syntheses is the large excess of the alkyl halide employed, which creates a problem with expensive reactants and large-scale synthesis (Scheme 2.1a).' Also, long reaction times diminish the efficiency of the reaction (Scheme 2.1b).^ Often, a purification step, usually recrystallization or washing, is required to obtain the product in sufficient purity. It should be noted that

17 .. ^"^^N-^^, CaHsBr (excess) ^^%^ (a) IN ^ [0,^-\ Br ^ 48 h, reflux ^^ ^

^^' U^N . |0N^ CI 72 h, 70 °C

Scheme 2.1. Literature preparations of l-alkyl-3-methylimdazolium halides.

imidazolium halides are extremely hygroscopic, which requires the use of inert atmosphere in the purification step or extensive drying.

( In this research, an efficient method for the preparation of l-alkyl-3- methylimidazolium halides and their structural analogues in high yields without

purification (see Scheme 2.2) was discovered.^ The short reaction time and use of neat

reactants makes this approach very attractive.

^"^^N-^ C4H9Br N 30min, 140°C

Scheme 2.2. Facile preparation of [C4-mim]Br (1) ionic liquid.

A key feature of this approach is the difference in the leaving group ability

between the chloride and bromide, the latter being the better leaving group. The

preparation of [C4-mim]Cl was reported by reaction of neat 1-methylimidazole and 1-

chlorobutane at 70 °C for 72 hours (Scheme 2.1b).^ With 1-bromobutane as the

alkylating agent, the desired salt was formed in quantitative yield in two hours at the

same temperature. Increasing the reaction temperature to 110 and then to 140 °C gave

18 quantitative yields of [C4-mim]Br in one hour and in 30 minutes, respectively.

Obviously, the use of 1-iodobutane would further facilitate the process. However, the cost of the iodoalkanes precludes their practical use.

With the conditions depicted in Scheme 2.2, a series of l-alkyl-3- methylimidazolium bromides was prepared (some of which are shown in Table 2.1).^ A

Table 2.1. Structures and yields of the l-alkyl-3-methylimidazolim bromides, [C„-mim]Br. Compound 1-Alkyl group Yield, %

2 C2H5 99

3 C3H7 99

1 C4H9 99

4 CgR.g 99

5 iso-C4H9 98

6 sec-CJig 67

7 CH2CH(CH3)C3H7 95

8 CH2CH2CH(CH3)C2H5 96

9 CH2CH(C2H5)C3H7 94 flask containing a magnetic stirring bar was charged with 1-methylimidazole and the primary alkyl bromide, immersed in an oil bath and heated to 140 °C during a period of

10 minutes. During the latter stages of the reaction, an exothermic reaction occurred leading an emulsion. This is caused by formation of the ionic liquid, which is immiscible with the residual reactants. The emulsion disappeared in a few minutes to produce a transparent, golden, slightiy viscous liquid. At this point, the bath was removed to

19 prevent darkening of the product and the solution was allowed to stir and cool for 10 minutes. The flask was then returned to the oil bath and heating at 140 °C was continued for 10-15 minutes. The resulting oil was dried under vacuum at 100-120 °C to afford the desired [C„-mim]Br for which the 'H NMR spectrum contained only the absorptions expected for the product. Primary bromides gave 94-99% yields of the corresponding imidazolium bromides. Under the same conditions, the reaction of 1-methylimidazole with 2-bromobutane gave only a 45% yield of [^ec-C4-mim]Br (6). Either loss of the low-boiling halide or a competing elimination reaction, facilitated by the high temperature, contributed to the lower yield. When the oil bath temperature was reduced to 70 °C and the reaction time was increased to 2 hours, the yield of the desired product increased to 67%. Further increase in the yield of [sec-C4-mim]BT (6) was possible by use of an excess of 2-bromobutane.

This developed procedure was extended to the preparation of l-aralkyl-3- methylimidazolium halides.^ It appeared that under the neat reaction conditions, some purification of the product salt was necessary. To avoid this purification step, a modified procedure was developed. Equimolar amount of the reactants were refluxed in benzene for 5-10 hours, as shown in Scheme 2.3.

^'^^N-^ CgHsCHsBr ^sC.^ IN • L^/N^ Br ^--^ 5 h, benzene, reflux ^~^ /T^

10 \=/

Scheme 2.3. Synthesis of [CgHjCH^-mimlBr (10) ionic liquid.

Since the salts are not soluble in benzene, but the reactants are, the solvent was decanted from the imidazolium halides, followed by washing with a fresh portion of benzene to

20 give the desired salts in high yields (Table 2.2). Longer reaction times were chosen to force the reaction to completion and thereby simplify purification of the resulting salt.

Due to these longer reaction times, reactivity differences between aralkyl chloride and bromide reactants were less important. Therefore, cheaper chlorides were utilized in some cases.

Table 2.2. Structures and yields for l-aralkyl-3-methylimidazolium halides, [C,H,(CH,)„-mim]X, with X=C1 or Br and [(CftHO.CH-mim]Cl. Compound 3-Aralkyl group Yield, %

10 CH2C6H5 95

11 (CH2)2C6H5 99

12 (CH2)3C6H5 95

13 CH(C6H5)3 85

Other methods for the preparation of l-alkyl-3-methylimidazolium halides have been reported. A sol vent-free route to ionic liquids using microwave (MW) irradiation was described." The use of a modem household microwave oven, equipped with inverter technology provided a way to obtain a set of [C„-mim]Br ionic liquids (see Scheme 2.4).

The reactivity trend of the alkyl halides was found to be the same as for the thermal method. The reaction times were 1-2 minutes, which is a great improvement over those

^3C.^^ C4H9X

MW (240W) X" = CI", Br-, r

Scheme 2.4. Microwave-assisted synthesis of [C„-mim]X ionic liquids.

21 for analogous the thermal reactions. Yields of the desired salts were similar to those obtained by the conventional thermal method (Table 2.3). A secondary alkyl bromide, 2-

Table 2.3. Structures, reaction times and yields of l-alkyl-3-methylimidazolium halides prepared under microwave and thermal heating." Alkyl halide MW Yield, % (time/s) Thermal Yield, % (time/h)"

C4H9C1 76 (90) 50(5)

C4H9Br 86 (75) 76(5)

C4H9I 92 (60) 93(3)

5ec-C4H9Br 89 (75) 61(5)

QH,3Br 71 (90) 78(5)

CgHpBr 91 (75) 73(5)

Oil bath at 80 °C.

bromobutane, used in excess to the 1-methylimidazole gave a lower yield than the primary alkyl halides. However, under the microwave irradiation [sec-C4-mim]Bi was produced in a higher yield than by heating. Mixing in the reaction vial was essential for an efficient process. The reaction mixture was taken out after initial irradiation, mixed and then heated again. This was repeated until a single phase was observed. The unreacted reactants were removed by diethyl ether washings. Collectively, utilization of microwave irradiation does not bring a lot of the improvement to the synthesis of 1-alkyl-

3-methylimidazolium halides.

The possibility of forming [C„-mim]Br ionic liquids under ultrasound irradiation was also investigated (Scheme 2.5). Both low intensity (LIU) and high intensity ultrasound (HIU) were employed. As expected, the reaction times were shorter with the

22 N |0N^ Br )))))(LIUorHIU)

Scheme 2.5. Synthesis of [Cj-mimJBr (3) ionic liquid under ultrasound irradiation. former, but still was measured in hours. The yields of the resulting salt were 80-90 % as determined by 'H NMR spectroscopy. The viscosity of [Cj-mimjBr contributes to the incomplete reaction. Thus, the thermal approach remains a superior way to prepare 1- alkyl(aralkyl)-3-methylimidazolium bromides.

To increase the diversity of structures for the imidazolium cation, other than 1- methylimidazole starting materials were required. Several methods for the preparation of

1-alkyUmidazoles are available (Scheme 2.6).^ These procedures are based on generating

(a) IN >• I N " I N '^^^^Z CHaCN, 24 h, r.t ^^^ CH3CN, r.t., 72 h ^*==/ 98%

,,, HN-^ i) CaHsONa, C2H5OH, r.t -"^N^ (b) I N .• I N ii) C2H5Br, reflux, 30 min 50%

HN^ i)NaH,THF,0°C /==^ /TV^N^ ^' L N '^^^Jl^ [^ Br ^ , r.t to 40 °C, 4 h 55%

Scheme 2.6. Examples of available synthesis for 1-substituted imidazoles.

the sodium salt, either separately or in situ. In the process of adapting these procedures to this research, certain disadvantages became evident. For the procedure shown in Scheme

23 2.6a, special care in drying the solvent, acetonitrile, was needed to obtain reproducible results.^" The long reaction times are also an unattractive feature for this procedure.

Also, with the higher alkyl bromides, a decrease in yield was evident. Longer alkyl chain halides lead to significant decreases in yield, when the procedure given in Scheme 2.6b was utilized.^'' The yields of 1-ethyl- and 1-propylimidazoles were in the range of 50%, and did not decrease on the scale up runs. The yield dropped to 39% for 1- pentylimidazole and 33% for 1-hexylimidazole obtained from 1-bromopentane and 1- bromohexane, respectively. This made the procedure impractical and it was abandoned.

A number of bis(imidazoles) substrates containing different aromatic linkers have been obtained with either NaH or t-BuOK in THE (Scheme 2.6c) in yields ranging from 50 to

65%.^" Benzylie-type bromides were essential for these reactions.

This procedure was modified to prepare 1-alkylimidazoles in this research

(Scheme 2.7). Yields of the 1- alkylimidazoles were fair to good as can be seen from the

^^.^ l)NaH,THF, 0°Ctor.t H2n+iCn. r N f N ^^ ii) CnH2n+iBr, reflux, 2 h ^==/

Scheme 2.7. Synthesis of 1-alkylimidazoles.

data in Table 2.4. The reaction worked well with all primary alkyl bromides. Secondary bromides, i.e.. sec-C^^x, failed to give satisfactory yields of the 1-substituted imidazole. The lower yield in the case of bromoethane can be explained by its volatility, which leads to some evaporation of the reactant. The yield decreased slightly in the case

24 Table 2.4. Yields of 1-alkylimidazoles.

Compound 1-Alkyl group Yield, %

14 C2H5 ^ 54

15 C3H7 55

16 C4H9 75

17 C5H,, 81

18 iso-C4H9 41 19 iso-CjH,, 72

of branched iso-C4H9Br. Apparently, steric bulkiness around the imidazole moiety

contributes to the effect, since iso-CjHnBr gave a higher yield of the alkylated product.

Also, the reaction gave a moderate 36% yield for 1-allylimidazole (20).

With these 1-alkylimidazolium bromides, the range of ionic liquids was extended

to [C„-C„im]Br by utilizing the previously developed procedure (Scheme 2.8). Due to a

H2n+lCn. ,^ CrT,H2m+lBr Hsn.iCn. VA L©N-CmH2...1 B, 120-140 °C, 30-50 min

Scheme 2.8. Synthesis of [C^-C„im]Br ionic liquids.

large number of ionic liquids, some of which are shown in Figure 2.1, the synthetic

procedure was slightiy modified. A heating mantie was used instead of an oil bath and

the reactions were visually monitored for the appearance of golden oils. The temperature

control was not as precise as before so longer reaction times were employed. Similarly,

l-aralkyl-3-alkylimidazolium chlorides were prepared (Figure 2.1).

25 n 2 n L@N-CrT,H2m.l 21 0N-C,nH2m.1 3 22 2 30 [Cm-C2im]Br Br" 3 31 4 23 [Cm-iso-C4im]Br 5 24 4 32 6 25 5 33 7 26 6 34 8 27 7 35 9 28 8 36 10 29 9 37 10 38

n n 2 39 H2n+lCnx 2 48 Br '^0N-C,nH2m+1 3 40 CI 3 49 4 41 [Cm-iso-CslmlBr 4 50 5 42 [(C6H5)2CH2-Cnlm]Br \ y 43 6 44 7 45 8 46 9 47 10

Figure 2.1. Structures of l-alkyl(aralkyl)-3-alkyUmidazolium halides.

2.2. Preparation of N-alkyKaralkyDpyridinium and -quinolinium Halides

Pyridinium-containing ionic liquids are not among the most widely used systems today, in spite of the pioneering discoveries made with this type of ionic liquids.^ Greater versatility for derivatizing imidazolium-based ionic liquids makes pyridinium-based ionic liquids less attractive. However, the low cost of the pyridine encourages continuation of research in this direction.^ Correlations within a series of N-substituted pyridinium ionic liquids would be useful in establishing the factors that govern the properties of this class of solvents. For this reason, a series of pyridinium-containing ionic liquids was prepared

(Scheme 2.9).

26 R-Br f^^ benzene, reflux, 5-6h ^N^ Br I R , with R = alkyl or aralkyl Scheme 2.9. Synthesis of N-substituted pyridinium bromides.

In general, the N-substituted pyridinium halides were found to be solids. They were not miscible with the solvent, benzene, and could be separated easily. Similar to the previously obtained data, alkyl and aralkyl chlorides tend to react with pyridine slower and generally give poorer yields as compared to the corresponding bromides. Some of the prepared N-substituted pyridinium salts are shown in Figure 2.2.

N + ••" O" [C4-Py]Br [C6H5(CH2)n-Py]Br [(C6H5)2CH-Py]CI

54 n X 54 1 CI 52 2 Br 53 Figure 2.2. Synthesized N-alkyl(aralkyl)pyridinium halides.

Recently, theoretical calculations were applied to predict the melting points of the ionic liquids.* A set of pyridinium bromides was chosen as model compounds. In general, the experimental and calculated melting points were in good agreement for 126 salts.

27 To further expand the range of ionic liquids, some N-substituted quinolinium salts were prepared (Figure 2.3). The synthetic procedure was similar to that used to prepare

[C4-Qu]Br [CeHsCHs-QuJCI

55 56 Figure 2.3. Synthesized N-alkyl(aralkyl)quinolinium bromides.

the N-substituted pyridinium salts. The N-substituted quinolinium bromides were intensely colored solids with fairly high melting points. Yields were in the range of 40-

50%. Reaction of quinoline with (C5H5)2CHC1 failed, apparentiy due to the increased steric demands.

2.3. Synthetic Routes to C^^-symmetric 1.3-Dialkylimidazolium Salts

Although our understanding of why ionic liquids have such low melting points is still incomplete, the unsymmetrical nature of the cation is believed to play a major role.'

Thus, the 100 °C lower melting points of l-ethyl-3-methylimidazolium salts than their N- butylpyridinium analogues have been attributed to the C2v-symmetry of the latter. By extension of such reasoning, 1,3-dialkylimidazolium salts that also have C^v-symmetry would seem to be poor candidates as room-temperature ionic liquids. In agreement, 1,3- disubstituted imidazolium halides are solids.'° Also, 1,3-dialkylimidazolium

28 hexafluorophosphates are reported to be solids at room temperature when the two alkyl groups are hexadecyl." Such salts with elongated alkyl groups are of interest because they exhibit liquid crystalline behavior above their melting points.

However, the choice of anion can play a dominant role in determining the phase transition temperatures of ionic liquids. It is important to determine requisite features for a symmetrical cation and an anion to produce a room temperature ionic liquid. This requires an arsenal of synthetic routes to symmetric 1,3-disubstituted imidazolium salts.

Several methods are known for the preparation of symmetrical ionic liquids."

However, they usually require several steps to obtain the starting materials. Furthermore, the products are often difficult to isolate in high purity. Imidazole-based starting materials are usually a matter of choice due to their availability and the simplicity of synthetic transformations. A simple, one-pot preparation of 1,3-dialkyl and 1,3- dibenzylimidazolium halides starting from N-trimethylsilylimidazole is shown in Scheme

2.10.'° The reaction afforded moderate to high yields of the desired products with all by-

(HaOsSi.^ RX R-^ ^ I N " l\t)N-R ^=/ toluene, 100 °C ^^

R = alkyl and aralkyl, X" = CI" and Br*

Scheme 2.10. Facile preparation of symmetric imidazolium ionic liquid from N-TMS-imidazole.

products either being volatile or soluble in toluene. In spite of this, there are a number of

drawbacks to this reaction. Two or more equivalents of the primary alkyl or benzyl

bromide are required. Secondary halides produced an excessive contamination of the

29 formed imidazolium halide. Hindered aliphatic and aryl halides failed to react. Also, a recrystallization step is usually required to get the pure materials.

A convenient and effective way to introduce a number of substituents into the commercially available imidazole has been discovered in this research (Scheme 2.11).'^

n 2 19 3 57 4 58 5 59 HN-^ i)NaH, THF, 0°Ctor.t H2n+iCn. ^'' 6 60 7 61 L N [©N-CnH2n.i ^^ ii)2CnH2n+iBr, reflux, 4-6 h ^~^ 8 62 9 63 10 64

Scheme 2.11. Developed synthetic route to Cj-symmetric 1,3-dialkylimidazolium ionic liquids from imidazole.

This is a slight modification of one described previously (see Scheme 2.7). Reaction of imidazole with one equivalent of sodium hydride in THF followed by the addition of two equivalents of a 1-bromoalkane and heating at reflux gave high yields (75-89%) of [(C^),- im]Br with n = 2-10. The products were hygroscopic oils or solids.

2.4. Introducing Functional Groups into Imidazolium Ionic Liquids

To obtain a comprehensive view of ionic liquids and fully understand the factors that can influence their properties, groups other than alkyl and aralkyl should be introduced onto the imidazolium cation. Several functional groups have been attached to imidazolium cations, giving the name "task-specific" ionic liquids (Figure 2.4).'" These ionic liquids have been utilized as co-solvents in metal-extraction experiments'"' and

30 C02-sponge type liquids.'"" Also, several ionic liquids derived from the antifungal drug miconazole were reported.'"'^^ Unfortunately, no applications of this exotic ionic liquid followed. While being quite interesting systems, these ionic liquids require fairiy elaborate synthetic routes.

PFe ^ ^S PFe ^-^ ^ o ^CH3 HN^ HN-C4H9

BF4 '-^ \-^ PFe ^-/ V^ o NH2 HN-^ /i=x HN—4^-CH3

Figure 2.4. "Task-specific" ionic liquids.

In this light, simpler and more readily available ionic liquids might be more promising. For such purposes, readily available halides were utilized to afford several functionalized ionic liquids (Scheme 2.12). The differences in reactivities between bromide and chloride containing substrates with 1-methylimidazole have been noted previously.^'" Usually that resulted in longer reaction times for the chlorides. In this situation, as expected, 2-bromoethanol reacted much faster with 1-methylimidazole than did 2-chloroethanol. When the methoxy-analogues were used, the differences become

31 ^ / CICH2CH2OH CICH2CH2OCH3 \ N?^ CI •^^' 70-80 °C, 5 h HO- dioxane, reflux, 12 h / -OCH3 65 67

^ / BrCH2CH20H BrCH2CH20CH3 \ ^ N^ Br 100-140°C, 30min 100-140 °C, 30 min l©"^ HO- -OCHa 66 68

Scheme 2.12. Preparation of hydroxy- and methoxy-containing imidazolium halides.

more significant. The reaction of 2-chloroethyl methyl ether with 1-methylimidazole failed to take place under neat reaction conditions. Carrying out the reaction in refluxing benzene or THF afforded a moderate yield of the desired product after an extended period of time. On the other hand, the corresponding bromo derivative afforded [MeO(CH2)2- mim]Br ionic liquid under neat reaction conditions in nearly quantitative yield over a short period of time. Some of these ionic hquids were reported in the literature,^'''^ but no distinctions were made on the reactivity of chlorides and bromides.

Fluorine-containing ionic liquids were prepared according to slightly modified literature procedures (see Scheme 2.13).'* The reaction of 1-methylimidazole andl,l,l,2,2,3,3,4,4,5,5,6,6-tridecafluoro-8-iodooctane was more efficient when performed in a solvent. An excess of the alkylating reagent was required to obtain a high yield of the product. This is a serious drawback, considering the high cost of the iodofluoroalkane. The reaction of 1-methylimidazole and fluorobenzyl iodide was fast

32 ICH2CH2C6F13 (excess) \ N THF, reflux, 10 h + )N- \ -CeF 69 13

BrCH2C5F5 '^f^N- ^ 100-140°C, 15 min

Scheme 2.13. Synthesis of fluorine-containing imidazolium halides

and clean under neat reaction conditions. In general, these fluorine-containing ionic liquids were immediately converted into other room-temperature ionic liquids using anion metathesis reaction.

Ionic liquids with a carboxyl-containing substituent on the imidazolium moiety are of interest due to the possibility of having the anionic and cationic moieties covalently attached to each other. However, this concept has not been applied to the ionic liquids as yet. For this reason, the preparation of carboxylic acid-containing ionic liquids was attempted (Scheme 2.14). The reaction was very inefficient with bromoacetic acid. The yield of the product 71, as determined by 'H NMR spectroscopy, in the crude reaction mixture, was less than 30%. Varying the reaction conditions (solvents, temperature and excess of the alkylating agent) did not improve this synthesis of [H02CCH2-mim]Br. The desired ionic liquid could only be isolated from the complex mixture by recrystallization from a mixture of the molecular organic solvents, i.e., methanol/acetonitrile/diethyl ether.

When 3-bromopropionic acid was used, the corresponding [H02C(CH2)2-mim]Br ionic liquid was obtained more efficiently. Apparently, neighboring-group participation has some effect on the alkylation process. Based on these results, the further the carboxylic

33 ^==/ different conditions ^

n 1 71 2 72 Scheme 2.14. Preparation of various carboxyl-containing imidazolium bromides.

group is from the imidazole moiety the more efficient is formation of the corresponding salt.

2.5. Synthesis of Dicationic Salts

Thus far, most of the attention in the field of ionic liquids has been concentrated on compounds with one cationic moiety. It is of interest to explore the possibility of having multiple cations in the structure of ionic liquids. It is well-known that imidazolium salts form carbenes in the presence of transition metals and cooperative action of the two imidazolium moieties might be beneficial. Some of bis-imidazolium salts have been shown to be quite versatile catalysts in a number of organic reactions.'^

The synthetic route to 1,3-disubstituted imidazolium ionic liquids^ was used to prepare a series of bis-imidazolium salts (Scheme 2.15). Conducting the reaction in benzene gave higher yields than the neat reaction, avoiding the recrystallization step. The linkage between the two imidazolium centers, as well as the nature of atoms in it, can be altered to achieve greater variety. Preparation of some bis-imidazolium dibromides under MW irradiation heating is also described in literature."

34 \ Br Br n -N(OV^X^Vr^N- 2Br- benzene, reflux, 1-3 h

1 73 2 74 3 75 Scheme 2.15. Synthesis of bis-imidazolium halides.

To further explore these interesting systems, a set of dicationic ionic liquids was prepared with two different positively charged moieties. This utilized easily synthesized

(a)-bromoalkyl)-trimethylammonium bromides as reactants.'^ The synthetic route for the preparation of both imidazolium and pyridinium-containing structures is shown in

Scheme 2.16. The yields are generally moderate to high. All of the dibromides are hygroscopic solids.

Br Br n N(CH3)3 2 76 benzene, reflux, 5 h N + 3 77 2 Br 4 78 N(CH3)3 5 79 + n 2 Br Br 80 N(CH3)3 2 Br 3 81 4 82 benzene, reflux, 5 h > N(CH3)3 5 83

Scheme 2.16. Preparation of unsymmetrical dicationic [(CH3)3N(CH2)n+|-mim]2Br and [(CH3)3N(CH2)n^,-Py]2Br ionic liquids.

35 2.6. Metathesis Reactions to Introduce Other Anions into Ionic Liquids Halide-containing ionic liquids find very limited application due to their physical properties. They are hygroscopic, very viscous oils or even solids at room temperature.

They have been used as solvents in the Heck reaction, which is conducted at elevated temperatures."' Some examples of using 1,3-disubstituted imidazolium halides as catalysts, co-solvents'^'' or even as solvent-reagent"' are also known.

i When a halide is substituted by another anion, the properties of the resulting ionic liquids change dramatically. Metathesis reactions allow a vast variety of ionic liquids to be prepared.^'"•^*'"-* Ease of separation and purification of the resulting ionic liquid becomes the major feature for determining the suitability of this reaction. Depending on the nature of the desired ionic liquid, several different metathesis reaction conditions can be utilized. Representative examples are shown in Table 2.5. Yields usually vary from moderate to almost quantitative. \

Table 2.5. Conditions for selected metathesis reactions.

Br HX or MX N^f+j, N conditions

X Water miscibility Reagent(Conditions) Ref.

N03- yes AgNOj (H2O, MeOH, r.t.) 20

BF4- varies AgBF4 (MeOH, r.t.), NaBF4 (HjO, r.t.) 20a, 21 PFr no NaPFg (acetone, r.t.), HPF^ (H.0,0-r.t.) 22,23

NTf2" no LiNTf2(H20,r.t.) 5b, 24

Co(CO)4" Na[Co(CO)4] (acetone, r.t., 24 h) 25

BPh4- no NaBPh4 (acetone, r.t.) 26

36 A main concern for the metathesis reaction is the purity of the resulting ionic liquid. The main contaminants are usually halide ions. For a number of applications their presence in the ionic liquid presents quite a concern. One way to overcome this problem is to titrate the ionic liquid with silver salts." This leads to precipitation, i.e., removal, of the halide ions in the form of their silver salts. This approach is also not perfect. The silver halides might have some limited solubility in ionic liquids. In some biological applications, even a very slight presence of a silver salt has a dramatic effect on the outcome of the process.^^

At present, hexafluorophosphate-containing ionic liquids are among the most widely used due to the ease of preparation and the versatility of the resulting ionic liquids. Introduction of the anion can be accomplished by metathesis reaction with either

KPFg or HPFg. Both reagents are commercially available and provide a convenient way to introduce the anion. However, both of these reagents afford ionic liquids that contain a number of contaminants. KPF^ contains significant amounts of alkali metal cations, which are introduced into the ionic liquids and are extremely hard to remove. The use of cheaper HPFg leads to the formation of HBr or HCl, which tend to absorb in the resulting ionic liquids. Also, HPFg contains some metal salts. (Washing with water is the most widely used method to remove the contaminants. However, this process is not very efficient. More importantiy, due to the solubility of the hexafluorophosphate ionic liquid, loss of the product into the aqueous phase takes place.

Considering these complications, a procedure for producing large quantities of alkali metal cation-free hexafluorophosphate ionic liquids was developed (Scheme

2.\1)?^ The metathesis reaction between an l-alkyl-3-methylimidazolium bromide and

37 1. HPFg, H2O, aomin 4 84 N?=^^, 2. phase separation N?=^ 5 85 ^N-CnH2n.i '- . LgN-CnH2n.i 3. (C2H5)3N (aq) ^^^ 6 86 7 87 4. washings 8 88 9 89

Scheme 2.17. Preparation of metal-free room-temperature ionic liquids.

aqueous HPFg (60%) was performed in a plastic bottle using doubly distilled, deionized, water. The two phases were separated, and the organic layer was washed with an aqueous solution of triethylamine to neutralized the HBr contained in the ionic liquid. This allowed acid-free ionic liquid to be obtained. At this stage, the ionic liquid contained significant levels of alkali metal salts, which came from the HPF^. So, it was dissolved in dichloromethane and vigorously stirred with water. Separating the layers and repeating the washing procedure afforded metal ion-free ionic liquid, as determined by ion chromatography.

2.7. Preparation of Deuterated Ionic Liquids

Deuterated solvents play an indispensible role in current organic chemistry and 'H

NMR spectroscopy. A number of chemical processes were elucidated by the use of 'H

NMR spectroscopic studies. Based on the ease of preparation, prices for deuterated solvents vary significantly. The investigation of chemical processes in ionic liquids is still is in its infancy. However, knowledge of reaction kinetics and reactive species, to name a few, will be of great value in the process of understanding the factors that govern reactions in ionic liquids.

38 "H NMR spectroscopy was utilized to monitor a number of oxidation reactions in a set of ionic liquids.^' The kinetics of these reactions were shown to be similar to those in conventional molecular organic solvents. This approach, however, presents a serious drawback, due to significant limitations of the deuterated reactants available and cost associated with them.

To date, there is no report of using deuterated ionic liquids as media for monitoring reactions by means of 'H NMR spectroscopy. In this view, the preparation and utilization of deuterated ionic liquids would be quite important. Also, the reusability of ionic liquid media would further decrease the cost of such deuterated solvents.

Recentiy, a facile preparation of several deuterated 1-substituded imidazoles and

1,3-disubstituted imidazolium salts was reported.^" The three-step procedure is outlined in Scheme 2.18. The first step of the formation of the Jj-1-methyl-imidazole was the

D D - HN-^ I.CD3OD, RuCl3(xH20)/(n-BuO)3P ^^^^N^ "^aDsl ^^'^^K,^ ' IN IN " J0N-C2D5 ^==/ 2. D2O, 10%Pd/C D'^\ D^^ D D Scheme 2.18. Synthetic route to deuterated imidazoles and imidazolium salts.

most crucial, proceeding with the lowest yield of 49%. The procedure utilized RuClj hydrate and CD3OD, which would be expensive for a large-scale reaction. It might have been worthwhile to use anhydrous RUCI3, instead of its hydrate, which probably could increase the yield of the coupling reaction. Also, the alkylation of imidazole took place in an autoclave, which presents an inconvenience from the practical point of view. In principle, the coupling reaction should proceed similarly with deuterated ethanol

(C2D5OD) as well. Deuteration of the imidazolium ring in the second step presents a very

39 efficient way to introduce deuterium into all positions of the imidazole ring. Alkylation of the substituted imidazole is a trivial synthesis, which is similar to the one done with undeuterated substrates.

A slightly different approach was undertaken in this research. Equipped with the knowledge of the factors that are responsible for the physical state of these salts, a few pyridinium ionic liquids were prepared according to Scheme 2.19. Although the presence

C2D5Br LiNTf2 ho " dio- 'N reflux, 4 h N D2O, r.t., 30 min y Br J NTfp 90

(CD3)2CDBr LiNTf? ds » ^2 N'+ Br * di2- ^N + ^N reflux, 4 h D2O, r.t., 30 min NTf2

91

Scheme 2.19. Synthesis of a deuterated pyridinium ionic liquids.

of several anions (i.e., as BF4~, NO3" and ""N(S02CF3)2) might provide room-temperature ionic liquids, only the last was considered. Bis(trifluoromethylsulfonyl)imide anion can conveniently be introduced, and more importantiy, affords non-hygroscopic ionic hquids with low viscosity. The utilization of commercially available starting materials, simplicity of approach and the possibility of carrying the reactions in one-pot are the main advantages over the available literature procedures.

40 2.8. Conclusions

With the goal of accessing the physical properties for an array of ionic liquids, efficient routes to their precursors have been developed. Facile preparation of 1- alkyl(aralkyl)-3-methylimidazolium bromides, which serve as precursors to other ionic liquids, was accomplished. This methodology was successfully applied to the synthesis of N-substituted pyridinium and quinolinium halides. A series of both symmetrical and unsymmetrical dicationic salts was prepared as well.

Also, synthetic preparations were adapted and developed for 1-alkylimidazoles.

These compounds were utilized for the synthesis of 1,3-disubstituted imidazolium- containing ionic liquids. This methodology was extended for the synthesis of C2- symmetric 1,3-disubstituted imidazolium salts and presents a superior route to these compounds.

Conditions for metathesis reactions were optimized in the effort to obtain other than halide-containing ionic liquids. With this methodology in hand, various ionic liquids were prepared in purities and quantities necessary for exploring properties and various applications of room-temperature ionic liquids. To facilitate research in the study of reaction mechanisms, kinetics, etc., in ionic liquids, facile preparation of several deuterated room-temperature ionic liquids was also accomplished.

2.9. Experimental Section

2.9.1. Materials

For the synthesis of ionic liquids, commercially available, reagent-grade starting materials from Aldrich or Acros were used as received, unless noted otherwise. Lithium bis(trifluoromethylsulfonyl)imide was purchased from 3M Company of St. Paul,

41 Minnesota. Deuterated molecular solvents from Cambridge Isotopes Laboratory were dried and stored over 4 A molecular sieves.

2.9.2. Physical and Analytical Methods

The 'H NMR spectra were recorded on Bruker AF-200, Bruker AF-300 or Varian

Unity INOVA 500 spectrometers at room temperature in D2O, CDCI3, dg-acetone or d^-

DMSO. 'H NMR chemical shifts are reported downfield from TMS. Multiplicities are abbreviated as s = singlet, d = doublet, t = triplet, quart = quartet, quint = quintet, sixt = sixtet and m = multiplet. IR spectra were recorded with a Perkin Elmer Model 1600 infrared spectrometer as films for oil and liquid samples or by deposits on a NaCl plate from dichloromethane or methanol solutions for solid samples. Melting points were obtained with a Mel-Temp melting point apparatus. Combustion analysis was performed by Desert Analytics Laboratory of Tucson, Arizona.

2.9.3. Synthesis of l-Alkyl(aralkyl)-3-methyl Imidazolium Halides 1-10 Compounds 1-10 were prepared according to procedures developed in this research.^ Spectral and combustion analysis data are consistent with the proposed structures.^

2.9.4. Procedure for the Synthesis of 1-Substituted Imidazoles 14-20 Sodium hydride (3.20 g, 80 mmol, 60% suspension in mineral oil) was washed with dry pentane under nitrogen. The reaction flask was placed in an ice bath. Freshly distilled THF (25 ml) was added followed by a slow addition of imidazole (5.00 g, 73

42 mmol) in 25 ml of freshly distilled THF. The reaction mixture was allowed to stir for 2-4 hours before being removed from the ice bath. Then the alkyl or allyl bromide (73 mmol) was slowly added at room temperature. The reaction mixture was refluxed for 4-6 hours, filtered, washed with fresh THF and filtered again. After THF was removed in vacuo, the liquid residue was distilled under reduced pressure through a 15-cm Vigreux column to give the pure product as a liquid. Note: Two and a half equivalents of alkyl bromide was used in the case of ethyl bromide and isobutyl bromide.

1-Ethylimidazole (14) was prepared in 54% yield as colorless liquid with bp 69-

70 °C/0.15 Torr. 'H NMR(CDCl3): 8 1.54 (t, J=7.3 Hz, 3H), 3.99 (quart, J=7.3 Hz, 2H),

6.93 (t, J=l .2 Hz, IH), 7.30 (s, IH), 7.48 (s, IH).

1-Propylimidazole (15) was prepared in 55% yield as a colorless liquid with bp

70-72 °C/1 Torr. 'H NMR(CDCl3): 8 0.89 (t, J=74 Hz, 3H), 1.80 (sixt, J=7.3 Hz, 2H),

3.89 (t, J=7.1 Hz, 2H), 6.91 (t, J=l .1 Hz, IH), 7.30 (s, IH), 7.45 (s, IH).

1-ButylimidazoIe (16) was prepared in 75% yield as a colorless liquid with bp

80-81 °C/0.5 Torr. 'H NMR(CDCl3): 6 0.93 (t, J=7.4 Hz, 3H), 1.32 (sixt, J=7.6Hz, 2H),

1.75 (pent, J=7.6 Hz, 2H), 3.92 (t, J=7.1 Hz, 2H), 6.90 (t, J=1.2 Hz, IH), 7.04 (t, J=1.0

Hz, lH),7.45(s, IH).

1-Pentylimidazoie (17) was prepared in 81% yield as a coloriess liquid with bp

99-100 °C/1 Torr. 'H NMR(CDCl3): 8 0.89 (t, J=7.2 Hz, 3H), 1.30 (m, 4H), 1.76 (pent,

J=7.3 Hz, 2H), 3.91 (t, J=7.1 Hz, 2H), 6.90 (s, IH), 7.04 (s, IH), 7.45 (s, IH).

1-IsobutylimidazoIe (18) was prepared in 41% yield as a colorless liquid with bp

71-73 °C/0.15Torr. 'H NMR(CDCl3): 6 0.92 (d, J=6.7 Hz, 6H), 2.02 (m, IH), 3.73 (d,

J=7.2 Hz, 2H), 6.89 (t, J=l .2 Hz, IH), 7.05 (t, J=0.8 Hz, IH), 7.44 (s, IH).

43 l-lsopentylimidazole (19) was prepared in 72% yield as a colorless liquid with bp 84-86 ''C/0.15 Torr. 'H NMR(CDCl3): 8 0.93 (d, J=8.1 Hz, 6H), 1.54 (m, IH), 1.65 (m,

2H), 3.94 (t, J=7.5 Hz, 2H), 6.90 (t, J=l .1 Hz, IH), 7.04 (s, IH), 7.45 (s, IH).

1-AUylimidazole (20) was prepared in 36% yield as a coloriess liquid with bp 70-

71 "C/O.IS Torr. 'H NMR(CDC1,): 8 4.53 (m, 2H), 5.20 (m, 2H), 5.93 (m, IH), 6.91 (m,

IH), 7.06 (m,lH), 7.46 (m,lH).

2.9.5. Synthesis of l-Alkyl-3-alkyr-imidazolium and l-Aralkyl-3-alkylimidazolium Halides 21-47

Compounds 21-47 were prepared according to procedure developed in this dissertation,^ with only slight modifications, unless noted otherwise.

To 37 mmol of 1-substituted imidazole, 37 mmol of an alkyl bromide or aralkyl chloride was added (111 and 74 mmol in the cases of ethyl bromide and propyl bromide, respectively). The mixture was heated at 80-100 °C with magnetic stirring until the formation of one transparent phase was observed. Heat was removed for 5-10 min, and the reaction mixture was allowed to cool, with stirring. Then the reaction flask was heated at 100 °C for additional 5-10 minutes to afford the pure product as an oil or solid.

[Cj-CjimlBr (21)" was prepared in 90% yield as an oily solid. 'H NMR (CDCI3):

8 1.63 (t, J=7.2 Hz, 6H), 4.47 (quart, J=74 Hz, 4H), 7.75 (d, J=1.6 Hz, 2H), 10.40 (s,

IH).

[C3-C2im]Br (22) was prepared in 99% yield as an oil. 'H NMR (CDCI3): 8 1.00

(t, J=74 Hz, 3H), 1.63 (t, J=74 Hz, 3H), 2.00 (sixt, J=7.4 Hz, 2H), 4.36 (t, J=5.8 Hz,

2H), 4.48 (quart, J=6.8 Hz), 7.66 (t, J=l .7 Hz, IH), 7.75 (t, J=l .7 Hz, IH), 10.44 (s, IH).

Anal. Calcld. for C8H,5BrN2 x O.lHjO: C 43.49, H 6.93, N 12.68, found C 43.34, H 7.22,

N 12.49.

44 [C4-C2im]Br (23) was prepared in 99% as an oil. 'H NMR (CDCI3): 8 0.97 (t,

J=7.3 Hz, 3H), 1.38 (sixt, J=7.4 Hz, 2H), 1.63 (t, J=74 Hz, 3H), 1.94 (pent, J=74 Hz,

2H), 4.39 (t, J=74 Hz, 2H), 4.46 (quart, J=74 Hz, 2H), 7.68 (t, J=1.7 Hz, IH), 7.80 (t,

J=l .7 Hz, IH), 10.37 (s, IH). Anal. Calcld. for C^H^BrNj x O.2H2O: C 45.66, H 741, N

11.83, found C 45.74, H 7.49, N 11.86.

[Cj-CjimlBr (24) was prepared in 99% yield as an oil. 'H NMR (CDCI3): 8 0.90

(t, J=6.3 Hz, 3H), 1.34 (m, 4H), 1.62 (t, J=7.3 Hz, 3H), 1.95 (m, 2H), 4.37 (t, J=74 Hz,

2H), 4.44 (quart, J=7.3 Hz, 2H), 7.59 (t, J=l .7 Hz, IH), 7.74 (t, J=1.7 Hz, IH), 10.39 (s,

IH). Anal. Calcld. for CloH.gBrN. x O.3H2O: C 47.55, H 7.82, N 11.09, found C 47.59, H

7.98,N 11.10.

[Cft-CjimlBr (25) was prepared in 99% yield as oil. 'H NMR (CDCI3): 8 0.87 (t,

J=6.8 Hz, 3H), 1.32 (m, 6H), 1.62 (t, J=74 Hz, 3H), 1.94 (m, 2H), 4.36 (t, J=7.4 Hz, 2H),

4.46 (quart, J=7.3 Hz, 2H), 7.60 (t, J=1.7 Hz, IH), 7.76 (t, J=l .7 Hz, IH), 10.35 (s, IH).

Anal. Calcld. for CnH2iBrN2 x O.IH2O: C 50.23, H 8.13, N 10.65, found C 49.93, H 8.28,

N 10.75.

[C^-CiimlBr (26) was prepared in 99% yield as an oil. 'H NMR (CDCI3): 8 0.87

(t, J=6.8 Hz, 3H), 1.28 (m, 8H), 1.62 (t, J=74 Hz, 3H), 1.94 (m, 2H), 4.37 (t, J=74 Hz,

2H), 4.47 (quart, J=7.3 Hz, 2H), 7.54 (t, J=l .7 Hz, IH), 7.71 (t, J=l .7 Hz, IH), 10.46 (s,

IH). Anal. Calcld. for C,2H23BrN2 x O.5H2O: C 50.69, H 8.51, N 9.85, found C 50.49, H

8.53, N 10.03.

[Cg-CzimlBr (27) was prepared in 99% yield as an oil. 'H NMR (CDCI3): 8 0.87

(t, J=6.8 Hz, 3H), 1.30 (m, lOH), 1.62 (t, J=74 Hz, 3H), 1.93 (m, 2H), 4.36 (t, J=74 Hz,

2H), 4.47 (quart, J=7.3 Hz, 2H), 7.56 (t, J=l .7 Hz, IH), 7.73 (t, J=l .7 Hz, IH), 10.37 (s.

45 IH). Anal. Calcld. for C|3H25BrN2: C 53.98, H 8.71, N 9.68, found C 54.03, H 8.89, N 9.71.

[C,-C2im]Br (28) was prepared in 99% yield as an oil. 'H NMR (CDCI3): 8 0.87

(t, J=6.8 Hz, 3H), 1.29 (m, 12H), 1.62 (t, J=74 Hz, 3H), 1.93 (m, 2H), 4.37 (t, J=74 Hz,

2H), 4.47 (quart, J=7.3 Hz, 2H), 7.56 (t, J=l .7 Hz, IH), 7.75 (t, J=1.7 Hz, IH), 10.44 (s,

IH). Anal. Calcld. for C,4H27BrN2 x O.2H2O: C 54.79, H 9.00, N 9.13, found C 54.68, H

9.06, N 9.09.

[Cio-CzimlBr (29) was prepared in 99% yield as an oil. 'H NMR (CDCI3): 8 0.87

(t, J=6.8 Hz, 3H), 1.29 (m, 14H), 1.62 (t, J=74 Hz, 3H), 1.93 (m, 2H), 4.36 (t, J=74 Hz,

2H), 4.49 (quart, J=7.3 Hz, 2H), 7.57 (t, J=1.7 Hz, IH), 7.78 (t, J=l .7 Hz, IH), 10.45 (s,

IH). Anal. Calcld. for C,5H29BrN2 x O.3H2O: C 55.83, H 9.25, N 8.68, found C 55.97, H

8.84, N 9.04.

[C2-iso-C4iin]Br (30) was prepared according to procedure developed in this dissertation,^ and gave spectroscopic and combustion analysis consistent with the proposed structure.

[C3-iso-C4im]Br (31) was prepared in 99% yield as a solid with mp 64-67 °C. 'H

NMR (CDCI3): 8 0.99 (m, 9H), 1.99 (m, 2H), 2.27 (m, IH), 4.21 (d, J=74 Hz, 2H), 4.38

(t, J=7.3 Hz, 2H), 7.64 (t, J=1.7 Hz, IH), 7.75 (t, J=1.7 Hz, IH), 10.45 (s, IH). Anal.

Calcld. for CioH^BrNzi C 48.59, H 7.75, N 11.33, found C 48.24, H 7.90, N 11.19.

[C4-iso-C4im]Br (32) was prepared in 99% yield as an oil. 'H NMR (CDCI3): 8

1.01 (m, 9H), 1.36 (m, 2H), 1.96 (m, 2H), 2.27 (m, IH), 4.21 (d, J=74 Hz, 2H), 4.38 (t,

J=7.3 Hz, 2H), 7.64 (t, J=1.7 Hz, IH), 7.75 (t, J=1.7 Hz, IH), 10.45 (s, IH). Anal.

Calcld. for C,,H2,BrN2: C 50.58, H 8.10, N 10.72, found C 50.39, H 8.33, N 10.71.

46 [Cs-iso-C4im]Br (33) was prepared in 99% yield as an oil. 'H NMR (CDCI3): 8

0.89 (t, J=7.2 Hz, 3H), 0.98 (d, J=8.8 Hz, 6H), 1.36 (m, 4H), 1.96 (m, 2H), 2.27 (m, IH),

4.19 (d, J=74 Hz, 2H), 4.39 (t, J=7.3 Hz, 2H), 7.64 (t, J=l .7 Hz, IH), 7.75 (t, J=l .7 Hz,

IH), 10.46 (s, IH). Anal. Calcld. for C,2H23BrN2: C 52.37, H 8.42, N 10.18, found C

52.36, H 8.66, N 9.94.

[C6-iso-C4im]Br (34) was prepared in 99% yield as an oil. 'H NMR (CDCI3): 8

1.00 (m, 9H), 1.29 (m, 6H), 1.95 (m, 2H), 2.27 (m, IH), 4.19 (d, J=74 Hz, 2H), 4.39 (t,

J=7.3 Hz, 2H), 7.56 (m, 2H), 10.56 (s, IH). Anal. Calcld. for C,3H25BrN2: C 53.98, H

8.71, N 9.68, found C 53.99, H 8.56, N 9.68.

[C7-iso-C4im]Br (35) was prepared in 99% yield as an oil. 'H NMR (CDCI3): 8

0.95 (m, 9H), 1.29 (m,8H), 1.93 (m, 2H), 2.27 (m, IH), 4.18 (d, J=74 Hz, 2H), 4.38 (t,

J=7.3 Hz, 2H), 7.63 (m, 2H), 10.51 (s, IH). Anal. Calcld. for C,4H27BrN2: C 55.44, H

8.97, N 9.24, found C 55.40, H 8.70, N 9.26.

[C8-iso-C4im]Br (36) was prepared in 99% yield as an oil. 'H NMR (CDCI3): 8

0.95 (m, 9H), 1.29 (m, lOH), 1.94 (m, 2H), 2.24 (m, IH), 4.21 (d, J=74 Hz, 2H), 4.37 (t,

J=7.3 Hz, 2H), 7.66 (m, 2H), 10.51 (s, IH). Anal. Calcld. for C,5H29BrN2: C 56.78, H

9.21, N 8.83, found C 56.81, H 9.31, N 8.89.

[C9-iso-C4iin]Br (37) was prepared in 99% yield as an oil. 'H NMR (CDCI3): 8

0.95 (m, 9H), 1.29 (m, 12H), 1.94 (m, 2H), 2.25 (m, IH), 4.21 (d, J=74 Hz, 2H), 4.39 (t,

J=7.3 Hz, 2H), 7.66 (m, 2H), 10.47 (s, IH).

[Cio-iso-C4im]Br (38) was prepared in 99% yield as an oil. 'H NMR (CDCI3): 6

0.94 (m, 9H), 1.20 (m, 14H), 1.94 (m, 2H), 2.25 (m, IH), 4.21 (d, J=74 Hz, 2H), 4.39 (t,

J=7.3 Hz, 2H), 7.74 (m, 2H), 10.42 (s, IH).

47 [C2-iso-Csim]Br (39) was prepared in 99% yield as an oil. 'H NMR (CDCI3): 8

0.99 (d, J=6.6 Hz, 6H), 1.64 (t, J=7.4 Hz, 3H), 1.84 (m, 2H), 4.34 (t, J=7.8 Hz, 2H), 4.47

(quart, J=74 Hz, 2H), 7.56 (t, J=l .6 Hz, IH), 7.73 (t, J=l .6 Hz, IH), 10.51 (s, IH). Anal.

Calcld. for C,oH,9BrN2: C 48.59, H 7.75, N 11.33, found C 4843, H 8.03, N 11.40.

[Cj-iso-CsimlBr (40) was prepared in 99% as a solid with mp 60-63 °C. 'H NMR

(CDCI3): 8 0.99 (m, 9H), 1.65 (m, IH), 1.86 (m, 2H), 2.00 (m, 2H), 4.38 (m, 4H), 7.65

(m, IH), 7.73 (m, IH), 10.48 (s, IH). Anal. Calcld. for C,,H2,BrN2: C 50.58, H 8.10, N

10.72, found C 50.68, H 7.88, N 10.62.

[C4-iso-C5im]Br (41) was prepared in 99% yield as an oil. 'H NMR (CDCI3): 8

0.96 (m, 9H), 1.38 (m, 2H), 1.65 (m, IH), 1.90 (m, 4H), 4.38 (m, 4H), 7.62 (t, J=l .8 Hz,

IH), 7.66 (t, J=1.8 Hz, IH), 10.51 (s, IH). Anal. Calcld. for Ci2H23BrN2: C 52.37, H

8.42, N 10.18, found C 52.14, H 8.55, N 10.14.

[Cs-iso-CsimlBr (42) was prepared in 99% yield as an oil. 'H NMR (CDCI3): 8

0.94 (m, 9H), 1.35 (m, 4H), 1.65 (m, IH), 1.92 (m, 4H), 4.38 (m, 4H), 7.66 (m, 2H),

10.51 (s, IH). Anal. Calcld. for C.jHjjBrNz: C 53.98, H 8.71, N 9.68, found C 54.15, H

8.74, N 9.62.

[Cfi-iso-CsimlBr (43) was prepared in 99% yield as an oil. 'H NMR (CDCI3): 8

0.86 (m, 3H), 0.95 (d, J=6.6 Hz, 6H), 1.30 (m, 6H), 1.62 (m, IH), 1.92 (m, 4H), 4.38 (m,

4H), 7.66 (m, 2H), 10.51 (s, IH). Anal. Calcld. for C,4H27BrN2: C 55.44 H 8.97, N 9.24, found C 55.45, H 8.91, N 9.25.

[C7-iso-Csim]Br (44) was prepared in 99% yield as an oil. 'H NMR (CDCI3): 6

0.86 (t, J=7.2 Hz, 3H), 0.98 (d, J=6.6 Hz, 6H), 1.30 (m, 8H), 1.65 (m, IH), 1.88 (m, 4H),

4.38 (m, 4H), 7.68 (m, 2H), 10.49 (s, IH). Anal. Calcld. for C,5H29BrN2: C 56.78, H

9.21, N 8.83, found C 56.75, H 9.30, N 8.88.

48 [Cg-iso-CsimlBr (45) was prepared in 99% yield as an oil. 'H NMR (CDCl,): 8

0.86 (t, J=7.2 Hz, 3H), 0.98 (d, J=6.6 Hz, 6H), 1.30 (m, lOH), 1.65 (m, IH), 1.89 (m,

4H), 4.40 (m,4H), 7.65 (m,2H), 10.49 (s, IH). Anal. Calcld. for C,6H3,BrN2: C 58.00, H

9.43, N 8.45, found C 58.10, H 9.25, N 8.56.

[Cj-iso-CsimlBr (46) was prepared in 99% yield as an oil. 'H NMR (CDCI3): 6

0.87 (t, J=7.2 Hz, 3H), 0.98 (d, J=6.6 Hz, 6H), 1.30 (m, 12H), 1.64 (m, IH), 1.90 (m,

4H), 4.48 (m, 4H), 7.62 (m, 2H), 10.50 (s, IH). Anal. Calcld. for C,7H33BrN2: C 59.12, H

9.63, N 8.11, found C 59.14, H 9.52, N 8.22.

[Cio-iso-CsimlBr (47) was prepared in 95% yield as an oil. 'H NMR (CDCI3): 8

0.87 (m, 3H), 0.98 (d, J=6.6 Hz, 6H), 1.30 (m, 12H), 1.64 (m, IH), 1.90 (m, 4H), 4.48

(m, 4H), 7.63 (m, 2H), 10.45 (s, IH). Anal. Calcld. for C,8H35BrN2: C 60.16, H 9.82, N

7.79, found C 59.90, H 10.11,N 7.78.

[(C5H5)2CH-C2im]Cl (48) was prepared according to procedure developed in this dissertation,^ and gave spectroscopic and combustion analysis data consistent with the proposed structure.

[(C5H5)2CH-C3im]CI (49) was prepared according developed in this dissertation procedure,^ followed by recrystallization form CHjCN-EtOAc mixture in 72% yield as a solid with mp 149-151 °C. 'H NMR (CDCI3): 8 0.89 (t, J=74 Hz, 3H), 1.90 (m, 2H), 4.26

(t, J=7.2 Hz, 2H), 7.07 (t, J=1.8 Hz, IH), 7.16 (m, 4H), 7.28 (m, 6H), 7.53 (s, IH), 7.63

(t, J=l .8 Hz), 10.71 (s, IH). Anal. Calcld. for CigH^iClN.: C 72.95, H 6.77, N 8.95, found

C 72.58, H 6.71, H 8.91.

[(C6H5)2CH-C4ini]Cl (50) was prepared according to developed in this dissertation procedure,^ in 75% yield as a solid with mp 115-117 °C. 'H NMR (CDCI3): 8

0.93 (t, J=7.3 Hz, 3H), 1.36 (sixt, J=7.5 Hz, 2H), 1.92 (pent, J=7.6 Hz, 2H), 4.35 (t, J=7.5

49 Hz, 2H), 7.14 (t, J=1.8 Hz, IH), 7.22 (m, 4H), 7.35 (m, 6H), 7.62 (s, IH), 7.67 (t, J=l .8Hz), 10.85 (s, IH). Anal. Calcld. for C30H23CIN2: C 73.49, H 7.09, N 8.57, found C 73.87, H 7.44, H 8.86.

2.9.6. Synthesis of N-Alkyl(aralkyl)pyridinium Halides 51-54

N-Alkyl(aralkyl)pyridinium halides were prepared according to procedure developed in this research.'

[C4-Py]Br (51) was prepared in 75% yield as an oily solid. 'H NMR (CDCI3): 6

0.97 (t, J=7.2 Hz, 3H), 1.46 (sixt, J=74 Hz, 2H), 2.08 (pent, J=7.5 Hz, 2H), 5.06 (t, J=7.4

Hz, 2H), 8.23 (t, J=6.6 Hz, 2H), 8.65 (t, J=7.8 Hz, IH), 9.72 (d, J=5.6 Hz, 2H).

[C6HsCH2-Py]Cl (52): was prepared in 90% yield as a solid with mp 98-99 °C.'H

NMR (CDCI3): 8 6.42 (s, 2H), 7.32 (m, 3H), 7.82 (m, 2H), 8.09 (t, J=6.6 Hz, 2H), 8.54 (t,

J=7,4 Hz, IH), 9.97 (d, J=6.3 Hz, 2H).

[CsH5(CH2)2-Py]Br (53) was prepared in 73% yield as a solid with mp 115-117

°C. 'H NMR (CDCI3): 8 3.41 (t, J=7.1 Hz, 2H), 5.28 (t, J=7.2 Hz, 2H), 7.22 (m, 5H), 7.99

(t, J=6.6 Hz, 2H), 8.50 (t, J=6.7 Hz, IH), 945 (d, J=5.5 Hz, 2H).

[(C6H5)2CH-Py]CI (54) was prepared in 70% yield as a solid with mp 192-194

°C. 'H NMR (dg-DMSO): 8 7.33 (m, 4H), 7.51 (m, 6H), 8.06 (s, IH), 8.25 (t, J=7.6 Hz,

2H), 8.73 (t, J=7.8 Hz, IH), 9.24 (d, J=5.6 Hz, 2H).

2.9.7. Synthesis of N-Alkyl(aralkyl)quinolinium Bromides 55-56

N-alkyl(aralkyl)quinolinium bromides were prepared according to procedure developed in this research.'

50 [C4-Qu]Br (55) was prepared in 60% yield as a solid with mp 137-141 °C. 'H

NMR (CDCI3): 8 0.98 (t, J=7.2 Hz, 3H), 1.55 (sixt, J=7.5 Hz, 2H), 2.11 (m, 2H), 5.45 (t,

J=7.5 Hz, 2H), 8.00 (t, J=7.7 Hz, IH), 8.26 (m, 2H), 8.48 (m, 2H), 9.28 (d, J=8.3 Hz,

IH), 10.50 (dd, J=4.6 Hz, J=l .2 Hz, IH).

[CftHsCHj-QulCI (56): was prepared in 40% yield as a solid with mp 138-141 °C.

'H NMR (CDCI3): 8 6.82 (s, 2H), 7.25 (m, 3H), 7.43 (m, 2H), 7.87 (t, J=74 Hz, IH),

8.13 (m, 2H), 8.37 (dd, J=6.9 Hz, J=1.3 Hz, IH), 8.56 (d, J=9.0 Hz, IH), 9.23 (d,

J=8.3Hz, IH), 10.89 (dd, J=4.5Hz, J=1.4Hz, IH). Anal. Calcld. for C,6H,4C1N: C 75.14,

H 5.52, N 5.48, found C 75.34, H 5.62, H 5.55.

2.9.8. Synthesis of Symmetric 1.3-Dialkylimidazolium Bromides 21 and 57-64

1,3-Dialkylimidazolium bromides were prepared according to developed in this dissertation procedure." Their spectral and combustion analysis data were consistent with proposed structures.

2.9.9. Synthesis of Ionic Liquids Containing Functional Groups 65-72

Preparation of [HO(CH2)2-mim]Cl (65): 2-Chloroethanol (4.21 ml, 62.7 mmol) was added slowly to 1-methylimidazole (5.00 ml, 62.7 mmol) and the mixture was heated at 70-80 °C for 5 h until the formation of a single phase was observed. The reaction mixture was cooled to room temperature affording an oily solid in 95% yield. 'H NMR

(dg-DMSO) 8: 3.59 (t, J=5.1 Hz, 2H), 3.76 (s, 3H), 4.20 (t, J=5.1 Hz, 2H), 7.73 (t, J=1.7

Hz, IH), 7.77 (t, J=1.7 Hz, IH), 9.13 (s, IH). Anal. Calcd. for CgHnClN.O: C 44.32, H

6.82, N 17.23, found C 44.30, H 6.92, N 17.25.

51 [HO(CH2)2-mim]Br (66) was prepared according to developed in this research procedure' in 98% yield as an oil, which solidified over time, mp 95-96 °C. 'H NMR (d^-

DMSO) 8: 3.69 (t, J=5.0 Hz, 2H), 3.85 (s, 3H), 4.23 (t, J=5.0 Hz, 2H), 7.73 (t, J=l .7 Hz,

IH), 7.76 (t, J=l .7 Hz, IH), 9.23 (s, IH).

[CH30(CH2)2-inim]Cl (67): 2-Chloroethanol (4.36 ml, 62.7 mmol) was dissolved in dry dioxane (50 ml) and 1-methylimidazole (5.00 ml, 62.7 mmol) was added via syringe. The mixture was refluxed for 12 h, then cooled to room temperature. THF was decanted and the oily residue was washed with fresh dioxane (3 x 30 ml) and dried using the benzene azeotrope method. This gave the desired product in 50% yield as an oily solid. 'H NMR (CDCI3) 8: 3.37 (s, 3H), 3.78 (t, J=5.0 Hz, 2H), 4.13 (s, 3H), 4.61 (t, J=4.9

Hz, 2H), 7.68 (t, J=l .6 Hz, IH), 7.74 (t, J=l .6 Hz, IH), 10.37 (s, IH).

[CH30(CH2)2-inim]Br (68) was prepared according to developed in this research procedure' in 99% yield as an oil, 'H NMR (CDCI3) 8: 3.38 (s, 3H), 3.79 (t, J=4.8 Hz,

2H), 4.14 (s, 3H), 4.61 (t, J=4.8 Hz, 2H), 7.72 (t, J=l .6 Hz, IH), 7.75 (t, J=l .6 Hz, IH),

10.01 (s, IH). Anal. Calcd. for C7H,3BrN20: C 38.03, H 5.93, N 12.67, found C 37.68, H

6.07, N 12.72.

[C5Fi3(CH2)2-mim]I (69) was prepared according to literature procedure, with the exception that a 10-h reflux time was utilized.'^ The product was used for further syntheses without isolation or purification. 'H NMR (dg-DMSO/CDClj) 8: 2.99 (m, 2H),

4.07 (s, 3H), 4.78 (t, J=74 Hz, 2H), 7.75 (s, IH), 7.99 (s, IH), 9.78 (s, IH).

[C5F5CH2-iniin]Br (70) was prepared according to a method developed in this research.' The product was used for further syntheses without isolation or purification.

'H NMR (CDCI3) 8: 4.13 (s, 3H), 5.84 (s, 2H), 7.65 (t, J=l .6 Hz, IH), 7.78 (t, J=l .6 Hz,

IH), 10.38 (s,lH).

52 [H02CCH2-mim]Br (71): 1-Methylimidazole (2.50 ml, 31.4 mmol) was dissolved in dry benzene (50 ml) and bromoacetic acid (9.31 g, 62.7 mmol) was added.

The mixture was refluxed for 12 h leading to formation of an oily precipitate. The reaction mixture was cooled to room temperature and the benzene was decanted. The oily residue was recrystallized several times from EtOAc/CH3CN/MeOH mixture to give the desired product in 26% yield as an oily solid. 'H NMR (d^-DMSO) 8: 3.96 (s, 3H),

5.27 (s, 2H), 7.82 (t, J=l .5 Hz, IH), 7.85 (t, J=l .5 Hz, IH), 9.30 (s, IH). IR: 3385, 3098,

2955,2600, 1740, 1624, 1577, 1400, 1237, 1175, 621 cm'.

[H02C(CH2)2-inim]Br (72): 1-Methylimidazole (1.00 ml, 12.5 mmol) was dissolved in dry benzene (50 ml) and 3-bromopropionic acid (2.58 ml, 25 mmol) was added. The mixture was refluxed for 6 h leading to formation of an oily precipitate. The reaction mixture was cooled to room temperature and the benzene was decanted. The oily residue was recrystallized from EtOAc/CH3CN/MeOH mixture to give the desired product in 35 % yield as an oily solid, which still had some starting material left as judged by 'H NMR) 'H NMR (dg-DMSO) 8: 2.93 (t, J=6.6 Hz, 2H), 3.88 (s, 3H), 4.37 (t,

J=6.6 Hz, 2H), 7.74 (t, J=1.7 Hz, IH), 7.82 (t, J=1.7 Hz, IH), 9.25 (s, IH). IR: 3380,

3090, 2955, 2600, 1740, 1624, 1577, 1407, 1239, 1177, 621 cm'.

2.9.10. Synthesis of Symmetric Dicationic Ionic Liquids 73-75 1-Methylimidazole (63 mmol) was dissolved in dry benzene (75 ml) and the reaction mixture was placed on ice bath. The a,co-dibromoalkane (32 mmol) in benzene

(10 ml) was slowly added through an addition funnel, and the reaction mixture was stirred for 30 min. The ice bath was removed and the mixture was refluxed for 1 to 3 h, before being cooled to room temperature. The benzene was decanted and the formed

53 solid was washed with fresh benzene (2 x 30 ml), followed by drying in vacuo. Note: the reaction is extremely exothermic, so special precautions should be taken while adding the a,cjo-dibromide to 1-methylimidazole.

[mim-(CH2),-mim]2Br (73) was prepared in 40% yield as a solid with mp 149-

152 "C, 'H NMR (J,-DMSO): 8 2.42 (m, 2H), 3.88 (s, 6H), 4.27 (t, J=6.9 Hz, 4H), 7.78

(t, J=l .6 Hz, 2H), 7.87 (t, J=l .7 Hz, 2H), 9.31 (s, 2H).

[mim-(CH2)4-mim]2Br (74) was prepared in 55% yield as a solid with mp 125-

127 "C, 'H NMR (^,-DMSO): 8 1.78 (m, 2H), 3.86 (s, 6H), 4.26 (t, J=6.9 Hz, 4H), 7.78

(t, J=1.8 Hz, 2H), 7.88 (t, J=1.8 Hz, 2H), 9.39 (s, 2H). Anal. Calcd. for C.^HjoBr^N^ C

37.92, H 5.30, N 14.74, found C 37.52, H 5.49, N 14.50.

[mim-(CH2)s-mim]2Br (75) was prepared in 57% yield as a solid with mp 136-

137°C,'HNMR(rf6-DMS0): 8 1.22 (m,2H), 1.85 (m, 4H), 3.87 (s, 6H), 4.19 (t, J=6.9

Hz, 4H), 7.74 (t, J=1.8 Hz, 2H), 7.82 (t, J=1.8 Hz, 2H), 9.24 (s, 2H). Anal. Calcd. for

C,3H22Br2N4 C 39.62, H 5.63, N 14.21, found C 39.59, H 5.84, N 14.06.

2.9.11. Synthesis of Non-symmetric Dicationic Ionic Liquids 76-83 Preparation of 76-79 ionic liquids: To a stirring solution of Br(CH2)„NMe3Br

(3.46 mmol) in 20 ml of methanol-benzene (1:10) mixture, pyridine (3.46 mmol) was added. The reaction mixture was refluxed for 24 h leading to a formation of an oily precipitate, which was separated by decantation and recrystallized from CH3CN-EtOAc to give white or yellow crystals.

[(CH3)3N(CH2)3-Py]2Br (76) was prepared in 64% yield as a solid with mp 238

"C. 'H NMR (D2O): 8 2.58 (m, 2H), 3.13 (s, 9H), 3.50(m, 2H), 4.72(t, J=7.9 Hz, 2H, partially overlapping with the residual peak of D.O), 8.10 (t, J=7.1 Hz, 2H), 8.58(t, J=7.9

54 Hz, IH), 8.89 (d, J=5.8 Hz, 2H). Anal. Calcd. for: C,,H2oN2Br2: C, 38.84; H, 5.93; N, 8.24, found: C, 38.84; H, 6.16; N, 8.17.

[(CH3)3N(CH2)4-Py]2Br (77) was prepared in 63% yield as a solid with mp 185-

188 °C. 'H NMR (D2O): 8 2.00 (m, 4H), 3.11 (s, 9H0, 3.39 (m, 2H), 4.68 (t, J=7.3 Hz,

2H0, 8.09 (t, J=7.0 Hz, 2H), 8.56 (t, J=7.8 Hz, IH), 8.88 (d, J=5.9 H, 2H). Anal. Calcd. for: C,,H22N2Br2: C, 40.70; H, 6.26; N, 7.91, found: C, 40.30; H, 6.63; N, 7.75.

[(CH3)3N(CH2)s-Py]2Br (78) was prepared in 58% yield as a solid with mp 164-

167 °C. 'H NMR (D2O): 8 1.42 (m, 2H), 1.85 (m, 2H), 2.10 (m, 2H), 3.09 (s, 9H), 3.31

(m, 2H), 4.64 (t, J=74 Hz, 2H), 8.07 (t, J=7.0 Hz, 2H), 8.52 (t, J=8.0 Hz, IH), 8.85 (d,

J=5.7 Hz, 2H). Anal. Calcd. for C,3H24N2Br2: C, 4241; H, 6.57; N, 7.61; found: C,

42.27; H, 6.87; N, 7.58.

[(CH3)3N(CH2)6-Py]2Br (79): Recrystallization of the crude product from

CH3CN-EtOAc failed to give a pure material. Therefore, the oil was dissolved in a minimum amount of MeOH at room temperature, and diethyl ether was added until two layers were formed. The upper white layer was decanted and the lower yellow layer was washed with fresh diethyl ether twice and then with benzene. This yellow oil was further recrystallized from benzene to give a pure product in 51 % yield as a light yellow solid with mp 104-107 "C. 'H NMR (D2O): 8 1.42 (m, 4H), 1.78 (m, 2H), 2.05 (m, 2H), 3.09

(s, 9H), 3.31 (m, 2H), 4.62, (t, J=7.4 Hz, 2H), 8.07 (t, J=6.9 Hz, 2H), 8.54 (t, J=7.6 Hz,

IH), 8.85(d, J=6.0 Hz, 2H). Anal. Calcd. for: C,4H25N2Br2: C, 44.00; H, 6.86; N, 7.33; found: C, 43.64; H, 7.25; N, 7.21.

Preparation of ionic liquids 80-83: To a stirred solution of Br(CH2)„NMe3Br (3.83 mmol) in methanol-benzene mixture (20 ml, 1:10) 1-methylimidazole (3.83 mmol) was added. The reaction mixture was stirred under reflux for 24 h to afford an oily

55 precipitate, which was separated by decantation and recrystallized from CHjCN-EtOAc or CHjCN-CfeHft to give a white solid.

[(CH3)3N(CH2)3-mim]2Br (80) was prepared in 47% yield as a solid with mp

199-200 °C. 'H NMR (D2O): 8 2.44 (m, 2H), 3.16 (s, 9H), 3.45 (m, 2H), 3.90 (s, 3H),

4.33 (t, J=6.3 Hz, 2H), 7.50 (d, J=10.8, 2H). Anal. Calcd. for C,oH2,N3Br2: C, 35.00; N,

6.17; N, 12.25, found: C, 34.86; H, 6.33; N, 12.06.

[(CH3)3N(CH2)4-miin]2Br (81) was prepared in 52% yield as a solid with mp

166-169 "C. 'H NMR (D2O): 8 1.88 (m, 4H), 3.08 (s, 9H), 3.34 (m, 2H), 3.86 (s, 3H),

4.24 (t, J=6.8 Hz, 2H), 7.44 (d, J=8.8 Hz, 2H). Anal. Calcd. for C,,H23N3Br2: C, 36,99; N,

6.49; N, 11.77, found: C, 37.08; H, 6.70; N, 11.50.

[(CH3)3N(CH2)5-mim]2Br (82) was prepared in 70% yield as a solid with mp

126-129 °C. 'H NMR (D2O): 8 1.37 (m, 2H), 1.84 (m, 4H), 3.07 (s, 9H), 3.28 (m, 2H),

3.85 (s, 3H), 4.19 (t, J=7.I Hz, 2H), 7.42 (d, J=7.8 Hz, 2H), 8.71 (s, IH). Anal. Calcd. for C,2H25N3Br2«H20: C, 37.04; N, 6.99; N, 10.80, found: C, 37.31; H, 7.32; N, 10.72.

[(CH3)3N(CH2)6-mim]2Br (83) was prepared in 28% yield as a solid with mp

124-127 °C. 'HNMR(D20): 8 1.38 (m,4H), 1.83 (m,4H), 3.08 (s, 9H), 3.27 (m, 2H),

3.87 (s, 3H), 4.18 (t, J=7.1 Hz, 2H), 7.43 (d, J=9.9 Hz, 2H), 8.70(s, IH). Anal. Calcd. for

C.jHzvNjBr,: C, 40.54; N,7.07; N, 10.91; found: C, 40.48; H,741; N, 10.67.

2.9.12. Synthesis of l-Alkyl-3-methylimidazolium Hexafluorophosphate IC^-mimlPF^ Room-Temperature Ionic Liquids 84-89

Ionic liquids 84-89 were prepared according to a procedure developed in this research,^' and gave spectral and combustion analysis data consistent with the proposed structures.

56 2.9.13. Synthesis of Deuterated Pyridine-Containing Room-Temperature Ionic Liquids 90 and 91

To deuterated pyridine (11 mmol), a deuterated alkyl bromide (17 mmol) was added and the mixture was refluxed for 4 h until a solid or a single liquid-like phase was formed. The reaction mixture was cooled to room temperature and dissolved in DjO (10 ml). LiNTfi (11 mmol) was added, and the mixture was stirred at room temperature for

30 min, before being extracted with dichloromethane (2 x 20 ml). Dichloromethane was removed under reduced pressure, and the resulting liquid was dried in vacuum at 0.15

Torr for 3-5h.

rf;9-[C2-Py]NTf2 (90) was obtained in 84% yield. 'H NMR (acetone): 8 1.67

(3H), 4.80 (2H), 8.25 (2H), 8.71 (1H),9.11 (2H). "C NMR (d^-acetone): 8 15.62,57.30,

116.93-124.59, 128.74, 144.63,145.98.

d,2-[iso-C3-Py]NTf2 (91) was obtained in 75% yield. 'H NMR (acetone): 8 1.73

(6H), 5.17 (IH), 8.26 (2H), 8.73 (IH), 9.21 (2H). "C NMR (d^-acetone): 8 21.90, 65.37,

117.02-124.69, 128.93, 143.37, 146.29.

2.10. References

1. J. S. Wilkes, J. A. Levisky, R. A. Wilson, C. L. Hussey, Inorg. Chem. 1982, 27,1263.

2. J. G. Huddleston, H. D. Willauer, R. P. Swatloski, A. E. Visser, R. D. Rogers, Chem. Commun. 1998, 1765.

3. S. V. Dzyuba, R. A. Bartsch, J. Heterocyclic Chem. 2001,5S, 265.

4. R. S. Varma, V. V. Namboodiri, Chem. Commun. 2001, 643.

5. (a) M. Begtrup, P. Larsen, Acta Chem. Scand. 1990, 44, 1050; (b) P Bonhote, A.-P. Dias, N. Papageorgiou, K. Kalyanasundaram, M. Gratzel, Inorg. Chem. 1996,35, 1168; (c) P. K. Dhal, F. H. Arnold, Macromolecules 1992,25, 7051.

57 6. T. Welton, Chem. Rev. 1999, 99, 2071.

7 The cost of pyridine is $ 6.0/500 ml (Acros) and the cost of N-methylimidazole is $ 60.9/485 ml (Acros).

8. A. R. Katritzky, A. Lomaka, R. Petrukhin, R. Jain, M. Karelson, A. E. Visser, R. D. Rogers, J. Chem. Inf. Comput. Sci. 2002,42,11.

9. K. R. Seddon, J. Chem. Technol. Biotechnol. 1997, 68, 351.

10. K. J. Harlow, A. F. Hill, T. Welton, Synthesis 1996, 697.

11. K. M. Lee, C. K. Lee, I. J. B. Lin, Chem. Commun. 1997, 899.

12. A. J. Arduengo, III, R. Krafczyk, R. Schmutzler, H. A. Craig, J. R. Goerlich, W. J. Marshall, M. Unverzagt, Tetrahedron 1999,55,14523 and references therein.

13. S. V. Dzyuba, R. A. Bartsch, Chem. Commun. 2001,1466.

14.(a) A. E. Visser, R. P. Swatloski, W. M. Reichert, R. Mayton, S. Sheff, A. Wierzbicki, J. H. Davis, Jr., R. D. Roger, Chem. Commun. 2001,135; (b) E. D. Bates, R. D. Mayton, I. Ntai, J. H. Davis, Jr., J. Am. Chem. Soc. 2002,124, 926; (c) J. H. Davis, Jr., K. J. Forrester, T. Merrigan, Tetrahedron Lett. 1998,39, 8955.

15. D. W. Armstrong, L.-K. Zhang, L. He, M. L. Gross, Anal. Chem. 2001, 73, 3679.

16. T. L. Merrigan, E. D. Bates, S. C. Scott, J. H. Davis, Jr., Chem. Commun. 2001, 2051.

17. (a) W. A. Herrmann, M. Elison, J. Fischer, C. Kocher, G. R. J. Artus, Angew. Chem. Int. Ed. Engl. 1995, 34, 2371; (b) M. W. Baker, B. W. Skelton, A. H. White, C. C. Williams, J. Chem. Soc, Dalton Trans. 2001, HI.

18. R. A. Bartsch, W. Zhao, Z.-Y. Zhang, Synth. Commun. 1999,29, 2393.

19. (a) A. J. Carmichael, M. J. Earle, J. D. Holbrey, P. B. McCormac, K. R. Seddon, Org. Lett., 1999, 7, 997; (b) J. Howarth, K. Hanlon, D. Fayne, P. McCormac, Tetrahedron Lett., 1997, 38, 3097; (c) R. X. Ren, J. X. Wu, Org. Lett. 2001, 3, 3727.

58 20. (a) J. S. Wilkes, M.J. Zaworotko, J. Chem. Soc, Chem. Commun. 1992, 965; (b) M. Fields, G. V. Hutson, K. R. Seddon, CM. Gordon, International Patent WO 98/06106.

21. J. D. Holbrey, K. R. Seddon, 7. Chem. Soc, Dalton Trans. 1999, 2133.

22. P. A. Z. Suarez, J. E. L. Dullius, S. Einloft, R. F. De Souza, J. Dupont, Polyhedron 1996,75,1217.

23. S. Chun, S. V. Dzyuba, R. A. Bartsch, Ana/. Chem. 2001, 73, 3737.

24. R. Hagiwara, Y. Ito, J. Fluorine Chem. 2000, 75, 221.

25. R. J. C. Brown, P. J. Dyson, D. J. Ellis, T. Welton, Chem. Commun. 2001, 1862.

26. J. Dupont, P. A. Z. Suarez, R. F. De Souza, R. A. Burrow, J.-P. Kintzinger, Chem. Eur.J.2000,6,2311.

27. G. S. Owens, M. M. Abu-Omar, Chem. Commun. 2000, 1165.

28. S. Park, R. J. Kazlauskas,y. Org. Chem. 2001, 66, 8358.

29. A. Durazo, M. M. Abu-Omar, Chem. Commun. 2002, 66.

30.C. H. Hardacre, J. D. Holbrey, S. E. J. McMath, Chem. Commun. 2001, 367, and references therein.

59 CHAPTER III

FINE-TUNING THE PHYSICAL PROPERTIES

OF IONIC LIQUIDS

The potential for fine-tuning various physical properties of ionic liquids by structural modifications within the anionic and cationic parts distinguishes these systems from conventional molecular solvents.' Knowledge of structure-property relationships in various series of ionic liquids would allow for the rational design of these solvents for specific applications. To achieve this goal, a comprehensive picture of fundamental physical properties is needed. Unfortunately, isolated literature accounts dealing with this aspect utilize incomplete series of ionic liquids.

The properties of any type of solvent depend on the amount of impurities and moisture that they contain. Therefore, it is important to recognize these issues in such complex systems as room-temperature ionic liquids. The main source of impurities in ionic liquids is most likely to come from starting materials for the anion metathesis step.

The water content will depend on the hygroscopicity of the ionic liquid.

The presence of a halide ion, which comes from the staring imidazolium halide, is a primary concern and is claimed to impact physical properties, such as the density and viscosity.- However, fairly large amounts of the halide impurities are needed to affect those properties to the appreciable extent. For example, the density of chloride-free [C4- mim]BF4 (1.23 g ml"' at 30 °C) decreases only to 1.17 g ml"' when more than 1 mol kg"' of [C4-mim]Cl was added.^ Also, considering the limit of the accuracy of the determination, this is a fairly small change in density. It should also be taken into consideration that halide-containing ionic liquids are extremely water soluble. Since the

60 present research deals primarily with water-immiscible hexafluorophosphate- and bis(trifluoromethylsulfonyl)imide-containing ionic liquids, which are prepared by metathesis reactions in water,' the amount of halide impurities is believed to be too low to affect any of the properties under consideration. For this reason, the halide-content was not determined.

Also, it should be noted that the inorganic salt or acid, such as LiN(S02CF3)2 and

KPFg utilized for anion metathesis reaction may contain a variety of alkali metal salts that are ultimately introduced into the formed ionic liquid. However, this type of impurities can be removed by extensive washings, utilizing procedures developed in this research."

Applications of purer reactants will lead to a decreased level of metal ion contamination in the product ionic liquid.

Another issue is with the water-content level in room-temperature ionic liquids.^"^

The water content of ionic liquids will have a varying effect on the properties of different ionic liquids. As one would expect, the properties of hygroscopic ionic liquids would be much more susceptible to the presence of water, than the properties of non-hygroscopic ones.^ Although hydrophobic ionic liquids, such as those containing PF^'-and NTf2~- anions, are water-imiscible, they still can absorb moisture from the air.^

It was of interest to determine to what extent these solvents can be dried. Several ionic liquids were selected for consideration, including [C2-mim]NTf2, [Cio-mimJNTf,,

[C4-mim]PF6 and [Cg-mimJPFg. This group of ionic liquids covers the most hydrophobic and most hydrophilic members of each series of l-alkyl-3-methylimidazolium hexafluorophosphate and bis(trifluoromethylsulfonyl)imide ionic liquids. A dichloromethane solution of the ionic liquid was shaken with distilled, deionized water and the dichloromethane was evaporated under vacuum. The residual ionic liquid was

61 divided into three portions, which were dried using three different methods: (a) dry under vacuum at 0.15 Torr for 5 hours at room temperature; (b) dissolution of ionic liquid in dichloromethane, followed by addition of MgS04, stirring for 3 hours, filtration, removal of the dichloromethane under vacuum and drying under vacuum at 0.15 Torr at 100 "C for 5 hours; (c) drying with a benzene azeotrope method followed by evaporation of the benzene under vacuum and vacuum drying at 0.15 Torr at 100 °C for 5 hours. All of the ionic liquids were obtained as almost moisture free - materials, since the water content, which was determined by Karl-Fisher titration, was less than 0.05%. For this reason, the simpler first drying method is advantageous over the more elaborate ones. Since ionic liquids can dissolve small amounts of inorganic salts, the second drying method might lead to potential contamination with magnesium salt.

In agreement with literature observations,^ all of these dried ionic liquids absorbed water from atmospheric air at ambient temperature when left on a bench top in open vials. The water content of such "water-saturated" room-temperature ionic liquids was in the range of 3-4% for less hydrophobic [Cj-mimjNTfj and [C4-mim]PF6 ionic liquids, and around 1% for more hydrophobic [Cg-mimJPFg and [Cio-mim]NTf2.

Furthermore, NTf2 -containing ionic liquids tended to absorb less moisture than PF^ - containing ionic liquids. This correlates with the more inert, more hydrophobic nature of the former anion.

In this research, the determinations of all physical properties were performed under atmospheric conditions. The ionic liquids were kept without special precautions on the bench top. Since the absorbance of moisture by ionic liquids takes place fairly rapidly, no attempt was made to dry the liquids before the physical properties

62 determinations was done. Therefore, the ionic liquids contained the maximum amounts of water that can be absorbed from the air.

3.1. Phase Transition Temperatures of Ionic Liquids

One of the most fascinating features of ionic liquids, which initiated research in this area, is the possibility of having a salt as a liquid at room temperature.* Also, the range of applications of these room-temperature ionic liquids can be significantiy broader than those of their higher melting analogues, the molten salts. Therefore, it is important to establish the factors responsible for lowering the phase transition temperatures of ionic liquids. Several accounts have addressed this issue. It was demonstrated that by elongating the alkyl chain length of the substituent on the l-alkyl-3-methylimidazolium and 1-alkylpyridinium ionic liquids significant changes in the phase transitions occurred.^

Distruption of the crystal lattice of l-alkyl-3-methylimidazolium carborane-containing ionic liquids was postulated to be responsible for decreasing the melting point.^ Visual and spectroscopic methods have been utilized to determine phase transition temperatures below room temperature.'"' However, more conveniently and accurately, the subambient melting points are measured by the use of differential scanning calorimetry (DSC).

Since the values for the phase transitions of ionic liquids depend on the amount of water present, special precautions should be taken while preparing samples for these determinations.^ For this reason, hygroscopic ionic liquids should be handled under inert conditions. On the other hand, the use of well-defined, non-hygroscopic ionic liquids will assure the reproducibility of the results and simplify the determination procedure.

For this reason, bis(trifluoromethylsulfonyl)imide- and hexafluorophosphate-containing

63 ionic liquids were utilized in this research to establish the structure-property relationships.

It is important to note that, being kinetic phenomena, the glass transition temperature of a room-temperature ionic liquid will depend on the cooling rate and conditions under which the sample is stored, as well as the heating rate. Also, the determination of phase transitions can be performed on heating or cooling the sample."

Due to the instrumentation utilized in this research, phase transitions of the ionic liquids were recorded on heating of the samples, which were cooled to sub-ambient temperatures with liquid nitrogen. The accuracy of these determinations is ±2 °C. Ionic liquids usually exhibit both glass transitions and melting points. The midpoint points of glass transitions, Tg, expressed as heat capacities, ACp, are taken into consideration in this research, as well as the melting points, designated as T„, expressed as enthalpies, AH.

3.1.1. Phase Transition Temperatures of l-Alkyl-3-methylimidazolium Hexafluorophosphates and Bis(trifluoromethylsulfonyl')imide Ionic Liquids

Phase transition temperatures for selected l-alkyl-3-methylimidazolium hexafluorophosphates, [C„-mim]PF6, with n = 2, 4, 6, 8 and 10, are reported in literature.^•''''•^' In this research, the complete series of these ionic liquids, [C„-mim]PF6, with n = 2-10, was prepared. The measured phase transitions are shown in Table 3.1.''"

As can be seen, the phase transition temperature can be fine-tuned over a very wide temperature range by simple structural variation within the imidazolium cation.

This is in agreement with literature data. However, particular distinctions should be mentioned as well. Although a glass transition temperature of 6 °C has been reported for

[C4-mim]PF6 ionic liquid (84),^' no phase transition in 0-10 °C region was observed under

64 Table 3.1. Phase transition temperatures of [C„-mim]PF6 ionic liquids.

Compound n Tg,°C(ACp,JK"'g-') T„,°C(AH,kJmol"')

92 2 58(7.1)

93 3 -74 (0.12) 21 (4.2)

84 4 -77(0.18)

85 5 -80 (0.16)

86 6 -80(0.13)

87 7 -84 (0.23)

88 8 -71 (0.07)

89 9 -66 (0.02) 14(5.8)

94 10 -71 (0.14) 32(7.1)

the chosen conditions to obtain a DSC trace in this research. Ionic liquids 92-94 are solids with melting points above room temperature. The remaining members of the series are liquids at ambient temperature. When liquid imidazolium hexafluorophosphates 84-

89 were kept in glass vials at -25 °C overnight, only [Cg-mimJPFg (89) solidified.

However, this ionic liquid went back into the liquid-like state at room temperature.

The influence of the anion on the phase transition temperatures was established by use of [C„-mim]NTf2 ionic liquids, with n = 2-10 (Table 2.3).' All of the ionic liquids in this series are liquids. This is not surprising, since bis(trifluoromethylsulfonyl)imide- anion is known to suppress the melting points of the ionic liquids.'^ This set of ionic liquids contrasts with that for the [C„-mim]PF6 series. The mid-points of the glass transitions do not vary appreciably as the alkyl chain-group is elongated. Thus, [C„- mim]NTf2 ionic liquids do not provide much information as to how the fine-tuning of the

65 Table 3.2. Phase transition temperatures of [C^-mimjNTfj room-temperature ionic liquids. Compound n Tg,"C (AC,, J K'g') T^,°C (AH,kJ mol"')

95 2 -78 (0.02) -21 (9.0)

96 3 -87 (0.23)

97 4 -87 (0.09) -6(7.0)

98 5 -85 (0.17) -9(1.1)

99 6 -84 (0.20) -

100 7 -85 (0.15) 7 (0.4)

101 8 -84(0.17)

102 9 -83 (0.19) 103 10 -83(0.13) -29(1.5) -2(14.6)

cation's structure affects their glass transitions and/or melting points.

3.1.2. Phase Transition Temperatures of l-Alkyl-3-alkyr-imidazolium Hexafluorophosphates

A set of [C„-C„im]PF6 ionic liquids was utilized to further probe the structural

features of ionic liquids that are responsible for subambient phase transition temperatures.

The first set of ionic liquids was derived from 1-ethylimidazole (Table 3.3). Ionic liquids

111 and 112, containing nonyl and decyl groups, possess shghtly lower Tg values as

compared to their analogues derived from 1-methylimidazole, 89 and 94, respectively.

Also, for ionic liquids 106-111, there is a plateau in Tg values, which contrasts with the

[C„-mim]PF6 ionic liquids 84-89. Although ionic liquids 108 and 110 possess melting

66 Table 3.3. Phase transition temperatures of [C„-C2im]PF6 ionic liquids.

Compound n Tg,"C (AC^, J K' g') T,,°C (AH,kJ mol"')

92 1 58(7.1)

104 2 70 (6.6)

105 3 -7 (0.34)

23 (3.17)

106 4 -77(0.13)

107 5 -73 (0.13)

108 6 -73 (0.12) 25 (0.58)

109 7 -73 (0.17)

110 8 -73 (0.18) 30 (0.26)

111 9 -73 (0.20)

112 10 -37 (0.22)

points slightly above room temperature, the Tg are the main transitions responsible for the physical state of these ionic liquids.

This example demonstrates that a very fine balance between the structure of the ionic liquids and their physical properties, such as phase transitions, is a general phenomenon. Subsequently, a series of ionic liquids derived from 1-propylimidazole was prepared and their phase transition temperatures are recorded in Table 3.4. As can be seen from these data, glass transition temperatures do not change appreciably as the alkyl group is elongated from butyl to decyl in ionic liquids 114-120. Also, no melting points are noted for these ionic liquids. Apparentiy, as the length of the alkyl chains on the imidazolium cation increases, less efficient packing of the anionic and cationic parts of

67 Table 3.5. Phase transition temperatures of [C„-isoC4im]PF(, ionic liquids.

Compound n Tg,°C(ACp,JK'g"') T„,°C(AH,kJmol-')

121 1 42 (5.7)

122 2 -70 (0.19)

123 3 -65(0.19)

124 4 -62 (0.17)

125 5 26 (4.3)

126 6 64(13.2)

127 7 45 (4.3)

128 8 7 (2.4)

129 9 -61 (0.16)

130 10 0 (4.2)

[C9- isoC4im]PF6,129, however, is yet to be established.

The phase transition profiles for [Cn-isoCjimJPF^ (Table 3.6) are in sharp contrast to those for [C„-isoC4im]PF6 ionic liquids. As can be seen from these data, ionic liquids

135,136,138 and 139 possess both glass transitions and melting points. Since all of these compounds are room-temperature ionic liquids, the main transitions should be glass transitions. Those ionic liquids that exhibited both Tg and T^ were kept in glass vials at

-25 °C for 3 hours or overnight. [Cs-isoCsimJPFg (135), [Ce-isoCjimlPFg (136) and [Cg- isoCsimJPFft (138) solidified over a 3-hour period at -25 °C, but went back to the liquid state when brought back to room temperature. [Cg-isoCsimJPFg (138) solidified overnight at -25 °C and became a liquid again at room temperature. Ionic liquids [CrisoCjimlPFe,

(137) and [Cio-isoCjimlPFs (140) did not solidify at all, even when kept at -25 °C for

69 Table 3.6. Phase transition temperatures of [Cn-isoCjimJPF^ ionic liquids.

Compound n Tg,°C(ACp,JK'g-') T„,°C(AH,kJmol-')

131 1 -65(0.14)

132 2 -67(0.15)

133 3 -68(0.18)

134 4 -65 (0.19)

135 5 -67(0.18) 23 (0.54)

136 6 -67 (0.20) -1.64(0.13)

137 7 -66 (0.14)

138 8 -65 (0.07) -3(1.64)

139 9 -73 (0.15) -3(0.51) 140 10 -74 (0.20)

overnight.

3.1.3. Phase Transition Temperatures of Svmmetric 1 •3-Dialkylimidazolium Hexafluorophosphate Ionic Liquids

In spite of the fact that our understanding of why ionic liquids have low melting points is incomplete, the unsymmetrical nature of the cation is believed to play a major role.* Thus, the 100 °C lower melting points of l-ethyl-3-methylimidazolium salts than their A^-butylpyridinium analogues have been attributed to the Cj^-symmetry of the latter.

By extension of such reasoning, 1,3-dialkylimidazolium salts that have C.-symmetry would seem to be poor candidates as room temperature ionic liquids. In agreement with that statement, 1,3-dihexadecylimidazolium hexafluorophosphate is reported to be solids at room temperature."

70 In this research, a set of 1,3-dialkylimidazolium hexafluorophosphates with Cjv- symmetric imidazolium cation were prepared and their phase transitions temperatures recorded.'" Results are shown in Table 3.7. As can be seen, changing the alkyl groups

Table 3.7. Phase transition temperatures of [(C^j-inilPF^ ionic liquids.

Compound n Tg, °C (ACp, J K'g') T„,°C (AH,kJ mol')

141 1 89 (6.8) 104 2 70 (6.6) 113 3 43 (6.3)

142 4 -69 (0.3) 143 5 -72 (0.2) 144 6 73 (8.8) 145 7 47 (5.2) 146 8 -80 (0.2) 19 (5.2) 147 9 -70(0.2) 11(5.4) 148 10 -27 (0.4) 16 (6.7)

from methyl (141) to ethyl (104) to propyl (113) leads to a melting point drop from 89 to

70 to 43 °C, respectively. This can be explained by poorer packing into the crystal lattice as the alkyl group is elongated. With dibutyl and dipentyl substituents, salts 142 and 143 are room temperature ionic liquids with only glass transitions evident. In sharp contrast, when the alkyl groups are elongated to hexyl in 144, a solid salt is obtained with the melting point of 73 °C and no glass transition. There is a remarkable, greater than 140 °C

71 difference between the phase transition temperatures for [(C5)2-im]PF6 and [(C6).-im]PF6.

Apparently the hexyl groups in [(C6)2-im]PF6 pack into the crystal lattice almost as well as methyl and ethyl groups. The behavior of the ionic liquids with hexyl groups is unique and has been observed on some instances by others.' The understanding of this phenomenon is yet to be established. As the alkyl groups are lengthened from hexyl to heptyl, the 73 "C melting point for the former diminishes to 47 °C. For [(Cg)2-im]PF6 and[(C9)2-im]PF6 ionic liquids with octyl and nonyl groups, respectively, both glass transitions and melting points were observed. When the alkyl groups are decyl ([(C,o)2- imJPF^ 148), there are two melting points, but both are below ambient temperature.

Since their melting points are below room temperature, [(Cg)2-im]PF6 (146), [(C,),- imlPFg (147) and [(C,o)2-ini]PF5 (148) can also be considered room-temperature ionic liquids.

Thus, for the first time, it was demonstrated that by fine-tuning the structure of the

C2-symmetric cation, it is possible to have ionic liquids that are in the liquid state at ambient temperature.'"

3.1.4. Phase Transition Temperatures of 1 -Aralkyl-3-methylimidazolium Hexafluorophosphate and BisCtrifluoromethylsulfonvDimide Ionic Liquids

Easily obtainable [C6H5(CH2)„-mim]PF6 and [C6H5(CH2)„-mim]NTf2 ionic liquids were studied. The results presented on Table 3.8.' [C6H5CH2-mim]PF6 (149) and

[C6H5(CH2)2-mim]PF6 (150) are solids with melting points of 128 and 103 °C, respectively. Their DSC-traces showed no transitions below their melting points.

[C6H5(CH2)3-mim]PF6 (151) was isolated as a viscous liquid with a glass transition midpoint at ^0 °C. When a sample was kept at -25 °C overnight in a plastic bottie, it

72 Table 3.8. Phase transition temperatures of [C6H5(CH2)„-mim]PF5 ionic liquids.

Compound n Tg,°C (ACp, J K'g') T„,°C (AH,kJ mol')

149 1 - 130(9.0)

150 2 103 (10.7)

151 3 52 (9.5)

solidified and remained solid when allowed to warm to room temperature. The DSC

trace of solid 151 exhibited a melting point at 52 °C. When the viscous liquid 151 was

cooled at -25 °C in a glass vial, crystallization failed to occur even after several weeks.

Apparently, the surface of the plastic bottle promoted the crystallization process. For the

series of [C6H5(CH2)n-mim]PF6 149-151 ionic liquids, the melting point was lowered

upon increasing the number of methylene groups between the terminal phenyl group and

the imidazolium nitrogen.

Quite different behavior was noted for the NTf,"-analogues (Table 3.9).'

Table 3.9. Phase transition temperatures of [C6H5(CH2)„-mim]NTf2 ionic liquids.

Compound n Tg,°C (ACp, J K ' g') T,, °C (AH, kJ mol')

152 1 -56(0.19) 153 2 38(5.43)

154 3 48 (14.2)

[C6H5CH2- mim]NTf2 (152) gave a DSC-trace with a glass transition midpoint at

-56 °C. The salt remained liquid after being kept at -25 °C overnight in a plastic bottie

and its DSC trace was unchanged. For [C6H5(CH2)2-mim]NTf2 (153), which was

73 obtained as a liquid, the DSC trace showed two phase transitions, i.e., a glass transition at

-59 "C and a melting point at 37 °C. Ionic liquid 153 formed a wax-like solid after being kept at -25 °C overnight in a plastic bottie. This wax-like solid remained solid on warming to room temperature and the DSC trace exhibited only one phase transition at 38

°C. [C6H5(CH2)3-mim]NTf2 154 was originally obtained as a liquid and its DSC trace showed only a glass transition at -63 °C. The liquid 154 solidified when kept at room temperature for two months in a plastic bottle. The DSC trace of this crystalline solid exhibited a melting point at 48 °C. Thus, increasing the number of methylene groups in the aralkyl group of [C6H5(CH2)n-mim]NTf2 ionic liquids produced an increase in the highest phase transition temperature of the salt. This effect is the opposite to the one observed for the analogous hexafluorophosphate ionic liquids 152-154.

Collectively, the phase transitions can be fine-tuned over a very wide range of temperatures to produce a whole range of compounds from solids melting above 100 "C to room-temperature ionic liquids with extremely low glass transition temperatures.

3.2. Densities of Room-Temperature Ionic Liquids

Density is an important characteristic of any liquid. Large density differences in the solvents can facilitate phase separation processes. Yet very limited information is known about the densities of ionic liquids. Densities of a few l-alkyl-3- methylimidazolium ionic liquids have been reported in literature.^'^ Several factors are thought to influence the density of ionic liquids. The size of the anion is believed to strongly influence the density of ionic liquids. This is shown by the data in Table 3.10.^

A smaller anion affords a less dense ionic liquid. It has also been found that elongation of the alkyl group leads to diminished density. This is because methylene

74 Table 3.10. Influence of the anion on the density of room-temperature ionic liquids at 25 "C. Ionic liquid d, g ml'

[C4-mim]Cl 1.08

[C4-mim]I 1.44

[C4-mim]BF4 1.12

[C4-mim]PF6 1.36

[C4-mim]NTf2 143

moieties are less dense than imidazolium ones.^

For potential applications of ionic liquids in phase separations, densities of hydrophobic, water-immiscible ionic liquids are of great interest and important. Such ionic liquids are the focus of this research. Also, from the practical point of view, the ease of handling these solvents during the density determinations makes hydrophobic ionic liquids very attractive systems. Although it was shown that even hydrophobic room-temperature ionic liquids absorb moisture when exposed to air," the amount of water absorbed did not have an appreciable influence on the density of water-immiscible ionic liquids, such as [C4-mim]PF6 and [C4-mim]NTf2.^

3.2.1. Densitv of l-Suhstituted-3-methvlimidazolium Room-Temperature Ionic Liquids

In this research, densities of [C„-min]PF6 ionic liquids 84-89 and 92-94 and [C„- mim]NTL, ionic liquids 95-103 were measured. The data are presented in Table 3.11.'

In agreement with literature, the density decreases as n is increased." In the series

of room-temperature ionic liquids, the density of the bis(trifluoromethylsulfonyl)imide-

75 Table 3.11. Density (d) of l-alkyl-3-methylimidazolium ionic liquids determined by an Anton-PAAR density measurement system. Compound n, [C„-mim]PF(, d, g ml' Compound n, [C„-mim]NTf2 d, g ml"'

92 2 solid 95 2 1.519

93 3 solid 96 3 1.475

84 4 1.368 97 4 1.436

85 5 1.326 98 5 1.403

86 6 1.292 99 6 1.372

87 7 1.262 100 7 1.344

88 8 1.237 101 8 1.320

89 9 1.212 102 9 1.299

94 10 solid 103 10 1.271

containing ionic liquid is higher than that of the corresponding hexafluorophosphate.

These results are in agreement with those reported in literature.^

The influence of attaching an aralkyl group onto the imidazolium cation on the

density was investigated with [Ph(CH2)3-mim]PF6 (151) and [Ph(CH2)n-mim]NTf2 (152-

154) room-temperature ionic liquids. For [Ph(CH2)3-mim]PF6 while in the liquid state,

the density was determined to be 1.407 g ml"'. This shows that the density of the aralkyl-

containing ionic liquids is higher compared to those containing just the alkyl substituents.

This observation is in agreement with an anticipated density of a phenyl moiety as

compared to methylene groups.

Further evidence of higher densities of aralkyl-containing ionic liquids comes

from the densities of [Ph(CH2)„-mim]NTf2 ionic liquids 152-154 shown in Table 3.12.'

76 Table 3.12. Densities of [Ph(CH2)„-mim]NTf2 ionic liquids.

Compound n Density, g ml'

152 1 1.49P

153 2 1470"

154 3 1.455'

" Measured with an Anton-PAAR density measurement system.'' Determined with 1.00 ml volumetric flask.

Also, the larger NTf2^-anion is responsible for producing more dense ionic liquids, as opposed to smaller PF^"-containing ionic liquids. The measurements should be taken with caution since 153 and 154 were found to solidify under special conditions.

3.2.2. Influence of Temperature on the Density of Selected Ionic Liquids Considering that two-phase separation processes might take place at elevated temperatures, it would be of interest to obtain an insight into the density behavior of ionic liquids at higher temperatures. For [C4-mim]PF6 (84), [C4-mim]NTf2 (97) and [PhCH2- mim]NTf2 (152) ionic liquids, densities were measured as a function of temperature over

a range of 25-50 °C in 5 °C increments (Table 3.13).' For all three ionic liquids, an essentially linear decrease in density was observed as the temperature increased. In principle, with the proper choice of both anion and cation, one can expect that at elevated

temperatures, the density of hydrophobic ionic liquids can reach that of water or lower.

77 Table 3.13. Temperature dependence of density for several ionic liquids.

Density, gml"'

TCC) 84, [C4-mim]PF, 97,, [C4-mim |NTf2 152, [PhCH2-mim]NTf2

25 1.368 1.436 1.491

30 1.362 1.430 1.484

35 1.356 1.423 1.477

40 1.350 1417 1.471

45 1.345 1410 1.464

50 1.339 1.404 1.458

Thus, fine-tuning of densities of ionic liquids is possible through structural variations of the cation and identity of the anion, as well as the temperature.

3.3. Viscosities of Room-Temperature Ionic Liquids

Van der Waals and hydrogen bonding interactions are believed to govern the viscosity of room-temperature ionic liquids.'" An increase of viscosity for various ionic liquids compared to molecular solvents was attributed to enhanced van der Waals forces relative to the hydrogen bonding.^ This balance can be fine-tuned by finding the proper combination of anion and cation. Low anion weight along with low anion basicity are necessary to obtain a room-temperature ionic liquid with low viscosity. In support of the latter factor, the viscosity of [C2-mim]NTf2 with an inert anion of moderate molecular weight has a lower viscosity than [C2-mim]CH3C02.'° Considering the cation influence on the viscosity of ionic liquids, low molecular weight and sufficient mobility of the

78 substituents of the imidazolium moiety are important. In agreement, the viscosity of [C4- mimlPFft is much lower than that of [Cg-mimJPFg ionic liquid.^

Collectively, the reported results suggest a complex relationship between the structure and dynamic viscosity of room-temperature ionic liquids. For comprehensive understanding, complete series of ionic liquids should be used in determining the influence of the structure on viscosity. However, literature accounts deal only with a limited number ionic liquids.

3.3.1. Influence of Structure of l-Alkyl(aralkyl)-3- methylimidazolium Ionic Liquids on Dynamic Viscosity

The coefficients of viscosity 17 (dynamic viscosity) values for [C„-mim]NTf2 with n = 2-10 and [Cn-mimJPFg with n = 4-9 were measured. The results for [C„-mim]NTf2 ionic liquids are given in Table 3.14.' The data for [C2-mim]NTf2 and [C4-mim]NTf2 are in agreement with those reported previously.^ An almost linear dependence of r^ as a function of the length of the alkyl group is observed for [C„-mim]NTf2. This closely correlates with the idea of greater viscosity for an increase of the molecular weight of the cation and decrease of the flexibility of the substitient. Also, the potential for stacking of the methylene units increasing from the [C2-mim]NTf2 through [C|o-mim]NTf2 should be considered. The importance of this type of interaction was demonstrated in the X-ray structure of [C|4-mim]PF6."

79 Table 3.14. Viscosity of [C„-mim]NTf2 ionic liquids at 25 "C.

Compound n Viscosity, cP

95 2 25

96 3 35

97 4 44

98 5 50

99 6 59

100 7 68

101 8 74

102 9 85

103 10 90

On the other hand, the dependence of ry as a function of the alkyl group chain

length is much more complex for the [C„-mim]PF6 ionic liquids (Table 3.15).' For room-

Table 3.15. Viscosity of [C„-mim]PF6 ionic liquids at 25 °C.

compound n Viscosity, cP

84 4 270

85 5 308

86 6 408

87 7 432

88 8 470

89 9 785

80 temperature ionic liquid possessing butyl through octyl substituents, a steady increase in viscosity is observed. However, there is a disproportionate increase in viscosity when the alkyl group is elongated from octyl in [Cg-mim]PF, (88) to nonyl in [Cg-mimJPFg (89).

Enhanced solid-like behavior of the latter might be responsible for the very high viscosity. Also, [Cs-mimlPF^ might be structurally more similar to the higher homologue

[C,o-mim]PF6, which is a low melting solid, than to the lower homologue [Cg-mimJPFg, which is a room-temperature ionic liquid.'

It is immediately apparent that the [C„-mim]PF6 ionic liquids 84-89 are much more viscous than their NTf2" analogues. This is also in agreement with literature values for isolated examples of these room-temperature ionic liquids.^ Furthermore, the more inert bis(trifluoromethylsulfonyl)imide anion is expected to afford less viscous ionic liquids.'" For both ionic liquid series, there is a general increase in viscosity as the length of the alkyl group is increased.

For liquid-like [Ph(CH2)„-mim]NTf2 room-temperature ionic liquids, a significant increase in viscosity was observed on going from n = 1 (rj = 113 cP) to n = 2 (77 = 187 cP) with a much smaller enhancement on going to n = 3 (17 = 196 cP).' It should be recalled that both [Ph(CH2)2-mim]NTf2 and [Ph(CH2)3-mim]NTf2 changed from liquids to solids over time or after being cooled. In the originally obtained liquid form, [Ph(CH2),- mimJPFg (151) was an extremely viscous liquid (77 = 5756 cP at 25 °C). This liquid crystalUzed when cooled at -25 °C in a plastic bottie.

3.3.2. Viscosity - Temperature Dependence for Various Room-Temperature Ionic Liquids An increase in temperature diminishes the strength of interactions between the cation and anion and should result in lower viscosity values.^'^

81 The influence of temperature on viscosity for [Cj-mimJPF^ (84), [C4-mim]NTf2

(97) and [PhCH2-mim]NTf2 (151) is shown in Table 3.16.' These room-temperature

Table 3.16. Temperature dependence of viscosity for several ionic liquids.

Viscosity, cP

T,°C 84, [C4-mim]PF6 97, [C4-mim]NTf2 152, [C6H5CH2-mim]NTf2

25 270 44 113

30 211 29 75

35 157 25 59

40 124 21 45

45 84 17 37

50 69 16 30 ionic liquids were chosen so as to probe the influence of the anion for [C4-mim]PF6 and

[C4-mim]NTf2 ionic liquids. The influence of the cation can be seen by comparing the behavior of [C4-mim]NTf2 and [PhCH2-mim]NTf2. For all three ionic liquids, the viscosity decreased markedly as the temperature was increased in 5 °C intervals in the range of 25-50 °C. At 50 °C, the viscosities are only about 20-35% of that at 25 °C.

These results suggest that slow mass-transfer processes occurring in ionic liquids at room temperatures due to high viscosity of ionic liquids will be accelerated at elevated temperatures.

82 3.4. Surface Tensions of Room-Temperature Ionic Liquids

The surface tension is an important liquid property. Examination of the surface properties of ionic liquids will be particularly valuable in understanding the mechanism of multiphase-catalytic processes, which are known to occur at the interface.'* Surface tensions of room-temperature ionic liquids did not receive a significant attention until recently when several research groups independently disclosed the results of surface tension measurements for several ionic liquids.'"^'*

Surface tension can be described as a linearly decreasing function with increasing temperature.'* At the same temperature for the same cation, an ionic liquid with a larger anion will exhibit higher surface tension. These data are summarized in Figure 3.1 .'*

45

40 •

E ^ 35 •

[omimHBrJ 30 •

25 • (C .iinimJtPFJ

20 —»— 350 370 270 290 310 330 T(K) Figure 3.1. Dependence of surface tensions of several ionic liquid as function of temperature.

Surface tension data for [C„-mim]NTf2 with n = 2-10 from this research are presented in Table 3.17.' The surface tension exhibits a uniform decrease as the alkyl

83 Table 3.17. Surface tensions of [C^-mimJNTfj ionic liquids at 25 "C.

Compound n Surface tension, 10"^ N m"

95 2 3.95

96 3 3.84

97 4 3.74

98 5 3.65

99 6 3.57

100 7 3.15

101 8 3.09

102 9 3.04

103 10 2.98

group is lengthened from 2 to 6 carbon atoms. Followed by an unusually large decrease in surface tension when the alkyl group is changed from a hexyl to heptyl group, uniform decreases are once again apparent as the alkyl group is increased from 7 to 10 carbons.

Unusual behavior of l-hexyl-3-methylimidazolium cation has been noted earlier in reports from other research groups.'^ With elongated alkyl groups, the surface tensions for [Cn-mim]NTf2 approach those of common organic solvents, such as benzene and chloroform, 2.885 10"^ and 2.714 10"^ N m"' at 20 °C, respectively.'^

For [C„-mim]PF6 room-temperature ionic liquids (Table 3.18), there is once again a much larger decrease in surface tension when the alkyl group is changed from hexyl to heptyl than for all other one-carbon elongations. The overall trend in surface tension as function of the structure of the imidazolium cation is similar to that observed for [C„- mimJPFg ionic liquids.

84 Table 3.18. Surface tensions of [Cn-mimJPFg room-temperature ionic liquids at 25 °C.

Compound n Surface tension, 10 - N m'

84 4 4.63

85 5 4.49

86 6 4.20

87 7 3.62

88 8 3.54

89 9 3.47

Collectively, these data in agreement with surface tensions reported in the literature.' The l-alkyl-3-methylimidazolium room-temperature ionic liquids with the more inert NTf2"-anion possess lower surface tension values than corresponding PF(,"- containing ionic liquids.

Surface tensions for [C6H5(CH2)„-mim]NTf2 ionic liquids 152 and 153 are recorded in Table 3.19.' The surface tension is observed to increase as the number of

Table 3.19. Surface tensions of [C6H5(CH2)„-mim]NTf2 ionic liquids. Compound n Surface tension, 10" N m"'

152 1 4.08

153 2 4.21

154 3 4.35 methylene units between the terminal phenyl group and the imidazolium nitrogen is increased. Thus, elongation of the aralkyl substituent produces an increase in surface

85 tension rather than the decrease noted with alkyl group elongation. However, the data for

[C6H5(CH2)2- mimJNTL (153) and [C6H5(CH2)3-mim]NTf2 (154) must be viewed with some caution since these ionic liquids turned to solids after time or upon cooling.

The surface tension for [C6H5(CH2)3-mim]PF6 (151), which was initially isolated as a liquid but changed to a solid on cooling at -25 °C in a plastic bottle, was 3.30 10^ N m"', which is lower than for the corresponding NTf2~ salt. This contrasts with the behavior noted above for [C„-mim]PF6 and [C„-mim]NTf2 in which the surface tension is always appreciably larger for the hexafluorophosphate salt. Also, considering the sparsity of literature data, the influence of the anion on the surface tensions of ionic liquids needs further refinement.

3.5. Polarities of Room-Temperature Ionic Liquids

The polarity of room-temperature ionic liquids is an area of current research interest. Both solvatochromic and fluorescent dyes have been utilized to estimate the polarity of these solvents.''^ Unlike other physical properties of ionic liquids, such as phase transition temperatures, viscosity, etc., which vary over wide ranges,'-' only small polarity changes have been reported. It was demonstrated that the polarities of l-alkyl-3- methylimidazolium-based ionic liquids, such as [C„-mim]PF6^° and [C„-mim]BF4'' with n

= 4, 6 and 8, do not change appreciably as the 1-alkyl group is elongated. Generally, a more hydrophobic ionic liquid has a lower polarity. Varying the anion has a somewhat greater effect.""' However, changing the anion alters an array of physical properties of ionic liquids, including their physical state, as well as miscibility with molecular solvents.

In either case, variation in polarity does not exceed one unit for a specific spectroscopic probe.

86 Therefore, a different approach was sought in this research to vary the polarity over a wider range. The introduction functional groups onto the imidazolium moiety was postulated to achieve this goal. A few isolated examples of l-X-3-alkylimidazolium salts are reported in which X contains a functional group." However, the influence of incorporating a functional group on the room-temperature ionic liquids polarity is unknown.

To evaluate the potential of functional group variation for producing significant polarity changes in room-temperature ionic liquids, the series of l-X-3- methylimidazolium bis(trifluoromethylsulfonyl)imides was prepared (Figure 3.2). For

Compound X Abbreviation 96 C3H, [C3-mim]NTf2 HaC^ N(S02CF3)2 103 [C,o-mim]NTf2 l^N-X C10H21 152 C6H5CH2 [C6H5CH2-mim]NTf2 155 CH30(CH2)2 [CH30(CH2)2-mim]NTf2 156 HO(CH2)2 [HO(CH2)2-mim]NTf2 157 G6F|3(CH2)2 [C6F,3(CH2)2-mim]NTf2

Figure 3.2. Structures of functionalized room-temperature ionic liquids.

the series of non-hygroscopic room-temperature ionic liquids, NTfj" was selected as the anion instead of PFg" due to the anticipated lower viscosity and lower phase transitions of the bis(trifluoromethylsulfonyl)imide ionic liquids.'' Synthesis of the room- temperature ionic liquids was accomplished by reactions of 1-methylimidazole with the appropriate organic bromides, followed by anion metathesis with LiN(S02CF3)2 in water.'-'"'" These ionic liquids are all free-flowing liquids at room temperature.

Polarities of the ionic liquids were measured with Reichardt's dye (Figure 3.3).^' This is

87 I II

Figure 3.3. Structures of solvatochromic dyes, i.e., the Reichardt's dye (I) and Nile Red (II) used in determining the polarity of ionic liquids. the most widely used dye for determining solvent polarity. The £^(30) values for ionic liquids 96,103,152, and 155-157 are given in Table 3.20. As can be seen, changing the

Table 3.20. Polarities of ionic liquids.

Compound ET-(30), kcal mol"' (k^^^, nm) E^R, kcal mol"' (k^^, nm)

96 52.0 (550.0) 52.2 (547.5)

103 51.0(560.5) 52.2(547.5)

152 52.5(546.0) 51.8(552.0)

155 54.1(528.0) 51.0(561.0)

156 614(455.5) 50.5(566.0)

157 54.6(524.0) 52.2(548.0)

X group produces a range of ET-(30) values from 61.4 kcal mol"' for hydroxy-containing

[HO(CH2)2-mim]NTf2 (156) to 51.0 kcal mol"' for [C,o-mim]NTf2 (103). This is the largest polarity range obtained to date for a series of structurally related room-

88 temperatures ionic liquids. In general, the trend follows the polarity of the functional group in the substituent X.

These data were further supported by the polarity measurements made with the

Nile Red dye (Figure 3.3),'" which is another common dye applied for the determining polarities of both molecular solvents and ionic liquids. The data are also included in

Table 3.20. Although, variations in the ENR values are not as broad as observed with

Richardt's dye, the polarity trend correlates well between the two dyes.

Further confirmation of the polarity trend was obtained from the interactions of

Reichardt's dye with 96,155 and 156 ionic liquids, which span the range of the ionic liquid polarities, by 'H NMR spectroscopy. By comparing the chemical shifts of the imidazolium protons of the ionic liquids in the absence and presence of the dye, a polarity trend can be established. Moreover, the two distinct singlets of Reichardt's dye, which are attributed to the pyridinium (downfield singlet) and the phenoxide (upfield singlet) rings,"' can be used for this purpose as well. Results are given in Table 3.21. A downfield shifts for the dye and H(2)-imidazolium proton signals for 96 and 155 suggest hydrogen bonding between these parts of the molecules. This is the primary interaction responsible for the change in polarity, in agreement with that postulated previously based on the UV-visible spectroscopy data.

An upfield shift for the other two imidazolium protons indicates their interaction with the phenyl moieties of the dye. On the other hand, when the dye is added to ionic liquid 156, an upfield shift for the H(2)-imidazolium proton along with disappearance of the hydroxy-hydrogen [HO(CH2)2-mim-mim]NTf2 signal indicates a chance of the mode of interaction between the ionic liquid and the dye. Now the primary mode of interaction becomes the hydroxyl-moiety, which is forcing the H(2)- imidazolium proton to enter the

89 Table 3.21. Chemical shifts of the imidazolium protons (III) with 10 % of the Reichardt's dye (IV) added and pure ionic room-temperature liquid (in parentheses) as 0.1 M solutions in J^-acetone and selected Reichardt's dye protons for O.IM solutions in 6^^-acetone." Ph W2) A^^^''^^

TIT /\ A^H(phen) III (4)H H(5) y 1 '^ Ph-'S^Ph "O

Compound H(2) H(4) H(5) H(py) H(phen)

none 8.474 6.807

96 9.168(9.051) 7.697(7.745) 7.752(7.785) 8.516 6.896

155 9.098(9.020) 7.687(7.716) 7.722(7.746) 8.531 6.986

156 9.013(9.033) 7.697(7.724) 7.733(7.763) 8.587 7.153

" The H(4)- and H(5)-imidazolium protons were assigned based on NOESY ID NMR experiments. shielding cone of an aromatic moiety of the dye. Thus, with the introduction of a HO-containing group onto the imidazolium cation, the H(2) —dye interaction is replaced by the OH—dye interaction, which causes an increase in polarity. Collectively, the information obtained by 'H NMR spectroscopic studies supports the polarity data obtained by use of the solvatochromic dyes.

3.6. Conclusions

Various physical properties of ionic liquids were examined in this part of the research, which was aimed at establishing structure-property relationships. To obtain organic salts that are liquid at ambient temperature, a fine balance between the structure

90 of the cation and phase transition temperatures was established. Importantly, for the first time, it was demonstrated that a lack of symmetry in the cation is not essential to obtain room-temperature ionic liquids. Also, the introduction of the branched substituents away from the cationic moiety tends to decrease the phase transition temperatures, affording room-temperature ionic liquids. In general, for l-alkyl-3-methylimidazolium hexafluorophosphate-containing ionic liquids, longer alkyl chain groups on both imidazolium nitrogens lower the main phase transitions. This also seems to be the case for l-aralkyl-3-methylimidazolium hexafluorophosphates for which elongation of the methylene-bridge in [Ce,H5(CH2)„-mim]PF6 ionic liquids 149-151 leads to a decrease in the melting point of the ionic liquids.

The influence of the anion on the phase transition temperatures was established by comparing the hexafluorophosphate-based ionic liquids 84-89, 92-94 and 149-151 with the corresponding [C„-mim]NTf2 and [C6H5(CH2)„-mim]NTf2 ionic liquids. Glass transitions are, primarily, the main phase transitions, responsible for the liquid-like state for the majority of ionic liquids 95-103. In contrast with [C6H5(CH2)„-mim]PF6 compounds 149-151, an increase in the number of methylene units between the imidazolium and phenyl moieties in 152-154 leads to an increase in the major phase transition temperature. Special conditions were used to transform liquid-like 153 and 154 in their more thermodynamically stable solid state.

The overall picture of influence of the structure of the cation on the phase transition temperatures is fairly complex. Also, anomalous behavior of several ionic liquids should receive further consideration.

The densities for several series of ionic liquids were investigated as a function of the anion, structure of the cation and temperature. NTf2"-containing ionic liquids are

91 more dense than the corresponding PF^ -room-temperature ionic liquids. With an increase in temperature, a nearly linear decrease of density is observed.

Viscosities for an array of structurally related room-temperature ionic liquids were determined as a function of anion, structure of the cation and temperature. The dynamic viscosity is much higher than those of the conventional molecular solvents.

However, it can significantly be reduced at slightly elevated temperatures. This is especially advantageous, when slow mass - transfer processes take place in ionic liquids at ambient temperatures.

Surface tensions for several sets of room-temperature ionic liquids were determined. For l-alkyl-3-methylimidazolium ionic hquids, general trends in surface tension values seem to be fairly well established for l-alkyl-3-methylimidazolium hexafluorophosphates and bis(trifluoromethylsulfonyl)imides. However, the introduction of aralkyl-groups produced a different trend.

Finally, structural variations for fine-tuning of polarity over a wide range were demonstrated. This involved substituents with various functional groups. The polarity trend obtained for these room-temperature ionic liquids was established by use of UV- visible and 'H NMR spectroscopic techniques.

In conclusion, correlations between the structure of ionic liquids and various physical properties were determined. By tailoring the structure of the cation, the properties of ionic liquids can be fine-tuned over wide ranges. This knowledge, although still empirical, will help in the rational design of ionic liquids with desired properties for specific applications.

92 3.7. Experimental Section 3.7.1. Materials

The ionic liquids were prepared by procedures described eariier in this dissertation. For synthesis of the ionic liquids, commercially available, reagent-grade starting materials from Acros or Aldrich were used as received. Deuterated solvents were dried and stored over 4 A molecular sieves. Solvatochromic dyes were purchased from

Fluka and used as received.

3.7.2. Physical and Analytical Methods

The 'H NMR spectra were recorded on Brucker AF-200, Bruker AF-300 or

Varian Unity INOVA 500 spectrometers at 25 °C in CDCI3 or d^-acetone and chemical shits are reported downfield from TMS. "F NMR spectra were recorded on a Varian

Unity INOVA 500 spectrometer at 25 °C in dg-acetone with CF3COOH in 0,0 as an external reference. Multiplicities are abbreviated as s = singlet, t = triplet, quart = quartet, quint = quintet, sept = septet and m = multiplet.

The measurements of physical properties were carried out at 25±0.1 °C, unless noted otherwise. Water content was determined by Karl-Fisher titration method, using a

Metier Toledo DL36 KF Coulometer with Aqua Star Coulomat A and Coulomat C

solutions as the average of two runs with values that varied within 5 %.

A Shimadzu DSC-50 differential scanning calorimeter with a LTC low temperature assembly was utilized. The sample (5-25 mg), which had been stored at room temperature before analysis, was sealed in an aluminum pan under air and cooled to

about -130 °C by pouring liquid nitrogen into the LTC unit under helium (30 ml min"').

Cooling to this temperature usually took 20-25 min. As soon as all of the liquid nitrogen

93 had evaporated from the LTC unit and the temperature started to rise spontaneously, heating was initiated at 30 "C min '. Heating was continued to 70 "C for liquid samples and to 130 or 160 °C for solid samples. Such a rapid heating rate was employed to obtain well-defined transitions and baseline. Densities were measured with either a 1.00-ml volumetric flask or an Anton-PAAR Density Measurement System, i.e., DMA 602 density measuring cell, DMA 60 density meter, and FTC 50 flow-through cooler or EX

220 non-refrigerated bath/circulator. The dynamic viscosity was measured with an

Ostwald viscometer. Surface tensions were measured at 25±0.1 °C by use of a capillary rise method. For polarity measurements, the dyes were dissolved in ionic liquids in a capped vial at room temperature under magnetic stirring. The X^^^ values were recorded on a Shimadzu UV 2401-PC spectrophotometer using 1-mm cuvettes at 25±0.1 °C.

Polarity of an ionic liquid was calculated using a reported method.^'-^"

3.7.3. Preparation of l-Alkyl-3-methylimidazolium Hexafluorophosphate and BisCtrifluoromethylsulfonyDimide Ionic Liquids

Ionic liquids 84-89,92-94 and 95-103 were prepared according to procedure developed in this dissertation from the corresponding l-alkyl-3-methylimidazolium bromides by metathesis reactions with HPFg and LiN(S02CF3)2, respectively.' These ionic liquids gave spectroscopic and combustion analysis data consistent with the proposed structures.

94 3.7.4. Preparation of l-Aralkyl-3-methylimidazolium Hexafluorophosphate and BisdrifluoromethylsulfonyPimide Ionic Liquids

Ionic liquids 149-151 and 152-154 were prepared according to developed in this dissertation procedures from the corresponding 1 -aralkyl-3-methylimidazolium bromides by a metathesis reactions with HPF^ and LiN(S02CF3)2, respectively.' These ionic liquids gave spectroscopic and combustion analysis data consistent with the proposed structures.

3.7.5. Preparation of l-Alkyl-3-alkyr-imidazolium Hexafluorophosphate Ionic Liquids

HPFg or KPFg was added to an equimolar amount of l-alkyl-3-alkylimidazolium bromide dissolved in distilled deionized water. The reaction mixture was stirred at room temperature for 30-40 min until either the precipitation or phase separation occurred. The water was decanted and the solid or oil was dissolved in dichloromethane. The solution was washed with distilled deionized water two-three times and evaporated in vacuo. The residue was dried by the benzene azeotrope method followed by evaporation of the benzene in vacuo and drying the resulting liquid or solid at 0.15 Torr of vacuum at 70-

100 °C.

[C3-C2im]PFs (105): 80% yield, 'H NMR (d^-acet): 8 0.96 (t, J=74 Hz, 3H), 1.57

(t,J=7.3 Hz,3H), 1.97 (sept, J=7.3 Hz, 2H), 4.31 (t, J=74 Hz, 2H),4.39 (quart, J=7.3 Hz,

2H), 7.75 (t, J=1.8 Hz, IH), 7.78 (t, J=1.8 Hz, IH), 9.00 (s, IH). IR: 3167, 3119, 2975,

2884, 1567, 1469,1166, 836, 557 cm'. Anal. Calcd. for CgH.jFgNjP: C 33.81, H 5.32, N

9.86, found C 33.60, H 5.37, N 9.82.

95 [C4-C2im]PF, (106): 87% yield, 'H NMR (d^-acet): 8 0.95 (t, J=7.3 Hz, 3H), 1.39

(sept, J=7.5 Hz, 2H), 1.56 (t, J=7.3 Hz), 1.94 (pent, J=7.6 Hz, 2H), 4.34 (m, 4H), 7.69 (t,

J=1.9Hz, 1H),7.71 (t,J=1.9Hz, IH), 8.88 (s, IH). IR: 3166, 3119, 2965, 2939, 2878,

1567, 1469, 1165, 836, 557 cm'. Anal. Calcd. for C9H,7F,N2P: C 36.25, H 5,75, N 9.39, found C 36.03, H 5.70, N 9.29.

[C5-C2im]PFg (107): 89% yield, 'H NMR (d^-acet): 8 0.89 (t, J=6.9 Hz, 3H), 1.36

(m, 4H), 1.57 (t, J=7.4 Hz,), 1.96 (m, 2H), 4.36 (m, 4H), 7.73 (m, 2H), 8.94 (s, IH). IR:

3166, 3119, 2960, 2939, 2873, 1566, 1469, 1165, 843, 557 cm"'. Anal. Calcd. for

C,oH,9F6N2P: C 38.47, H 6.13, N 8.97, found C 38.34, H 6.23, N 8.96.

[C6-C2im]PF,(108): 90% yield, 'H NMR (d^-acet): 8 0.86 (m, 3H), 1.33 (m, 6H),

1.56(t,J=7.3Hz,3H), 1.95 (m, 2H), 4.35 (m, 4H), 7.71 (m, 2H), 8.90 (s, IH). IR: 3165,

3118, 2960, 2932, 2861, 1566, 1467, 1164, 837, 557 cm"'. Anal. Calcd. for C,,H2,F(,N2P:

C 40.49, H 6.49, N 8.59, found C 40.37, H 6.52, N 8.61.

[C7-C2im]PF6(109): 91 % yield, 'H NMR (d^-acet): 8 0.87 (m, 3H), 1.34 (m, 8H),

1.56 (t, J=7.3 Hz, 3H), 1.95 (m, 2H), 4.34 (m, 4H), 7.70 (m, 2H), 8.90 (s, IH). IR: 3165,

3119,2960,2930,2859, 1576, 1469, 1164, 834, 558 cm"'. Anal. Calcd. for C,2H23FeN2P:

C 42.35, H 6.81, N 8.23, found C 42.39, H 6.71, N 8.32.

[Cg-CiimlPFfi (110): 87% yield, 'H NMR (d^-acet): 8 0.87 (m, 3H), 1.34 (m,

lOH), 1.56 (t, J=7.3 Hz, 3H), 1.96 (m, 2H), 4.36 (m, 4H), 7.74 (m, 2H), 8.96 (s, IH). IR:

3165, 3118, 2960, 2928, 2858, 1576, 1467, 1164, 837, 557 cm"'. Anal. Calcd. for

C,3H25F6N2P: C 44.07, H 7.11, N 8.91, found C 44.46, H 7.35, N 7.84.

[C,-C2im]PF6(lll): 91% yield, 'H NMR (d^-acet): 8 0.87 (m, 3H), 1.35 (m,

12H), 1.56 (t, J=74 Hz, 3H), 1.96 (m, 2H), 4.37 (m, 4H), 7.76 (m, 2H), 9.01 (s, IH). IR:

96 3165, 3118, 2960, 2936, 2855, 1566, 1467, 1164, 836, 557 cm'. Anal. Calcd. for

C,4H27F,N2P: C 45.65, H 7.39, N 7.61, found C 45.60, H 7.51, N 7.96.

[Cjo-CzimlPF, (112): 90% yield, 'H NMR (d^-acet): 8 0.87 (m, 3H), 1.31 (m,

14H), 1.58 (t, J=7.3 Hz, 3H), 1.97 (m, 2H), 4.39 (m, 4H), 7.79 (m, 2H), 9.06 (s, IH). IR:

3165, 3119, 2960, 2926, 2855, 1567, 1465, 1165, 837, 557 cm"'. Anal. Calcd. for

C,5H29F6N2P: C 47.12, H 7.64, N 7.33, found C 47.51, H 7.92, N 741.

[C4-C3im]PF5(114): 85% yield, 'H NMR (d,-acet): 8 0.95 (m, 6H), 1.39 (m, 2H),

1.95 ( m, 4H), 4.33 (m, 4H), 7.30 (m, 2H), 8.93 (s, IH). IR: 3163, 3117, 2967, 2940,

2879, 1566, 1466, 1165, 836, 557 cm'. Anal. Calcd. for C,oH,9F6N2P: C 38.47, H 6.13, N

8.97, found C 38.16, H 6.27, N 8.97.

[C5-C3im]PF, (115): 89% yield, 'H NMR (d^-acet): 8 0.93 (m, 6H), 1.35 (m, 4H),

1.99 ( m, 4H), 4.32 (m, 4H), 7.34 (m, 2H), 8.96 (s, IH). IR: 3161, 3117, 2962, 2940,

2874, 1565, 1458, 1164, 836, 557 cm"'. Anal. Calcd. for C||H2,F6N2P: C 40.49, H 6.49, N

8.59, found C 40.13, H 6.69, N 8.67.

[Cs-C3im]PFs(116): 85 % yield, 'H NMR (d^-acet): 8 0.87 (m, 3H), 0.95 (t, J=74

Hz, 3H), 1.34 (m, 6H), 1.97 (m, 4H), 4.33 (m, 4H), 7.34 (m, 2H), 8.94 (s, IH). IR: 3162,

3118,2960,2935,2862, 1566, 1468, 1164, 836, 557 cm'. Anal calcd for C,2H23F6N2P: C

42.35, H 6.81, N 8.23, found C 42.07, H 6.96, N 8.37.

[C7-C3im]PF(i (117): 78% yield,'H NMR (d^-acet): 8 0.87 (m, 3H), 0.96 (t, J=74

Hz, 3H), 1.35 (m, 8H), 2.01 (m, 4H), 4.34 (m, 4H), 7.76 (m, 2H), 9.00 (s, IH). IR: 3162,

3117,2957,2931,2859, 1566, 1467, 1164, 836, 557 cm"'. Anal. Calcd. for C,3H25F6N2P:

C 44.07, H 7.11, N 7.91, found C 44.42, H 7.21, N 8.69.

[C8-C3iin]PF5 (118): 86% yield,'H NMR (d^-acet): 8 0.87 (m, 3H), 0.96 (t, J=74

Hz, 3H), 1.32 (m, 8H), 1.98 (m, 4H), 4.33 (m, 4H), 7.76 (m, 2H), 9.02 (s, IH). IR: 3161,

97 3117, 2929, 2851, 1566, 1466, 1164, 836, 557 cm"'. Anal. Calcd. for C,4H27F6N2P: C 45.65, H 7.39, N 7.61, found C 45.94, H 7.66, N 7.59.

[C,-C3im]PF, (119): 79% yield, 'H NMR (d,-acet): 8 0.88 (m, 3H), 0.95 (t, J=74

Hz, 3H), 1.32 (m, 12H), 1.96 (m, 4H), 4.33 (m, 4H), 7.74 (m, 2H), 8.97 (s, IH). IR: 3160,

3117, 2926, 2856, 1566, 1466, 1164, 835, 557 cm'. Anal. Calcd. for C,5H29F,N2P: C 47.12, H 7.64, N 7.33, found C 46.95, H 7.91, N 7.92.

[C,o-C3im]PF, (120): 70% yield, 'H NMR (CDCI3): 8 0.87 (m, 3H), 0.95 (t, J=7.3

Hz, 3H), 1.28 (m, 14H), 1.89 (m, 4H), 4.16 (m, 4H), 7.34 (m, 2H), 8.56 (s, IH). IR: 3162,

3118, 2926, 2856, 1566, 1466, 1165, 837, 557 cm'. Anal. Calcd. for C,6H3,F6N2P: C

48.48, H 7.88, N 7.07, found C 48.69, H 7.92, N 7.10.

[iso-C4-mim]PF6 (121): 85% yield, 'H NMR (d^-acet): 8 1.01 (d, J=6.6 Hz, 6H),

2.26 (m, IH), 4.16 (s, 3H), 4.05 (d, J=7.3 Hz, 2H), 7.70 (m, 2H), 8.92 (s, IH). IR: 3158,

2967, 1567, 1471, 832, 557 cm'.

[C2-iso-C4im]PF5(122): 89% yield, 'H NMR (d^-acet): 8 0.97 (d, J=6.7 Hz, 6H),

1.59 (t, J=9.2 Hz, 3H), 2.25 (m, IH), 4.19 (d, J=7.3 Hz, 2H), 4.42 (quart, J=74 Hz, 2H),

7.76(t,J=1.8Hz, 1H),7.81 (t, J=1.8Hz, IH), 9.04 (s, IH). IR: 3162,3118,2967,2880,

1565, 1471, 1164, 836, 557 cm"'. Anal. Calcd. for C9H,7F6N2P: C 36.25, H 5.75, N 9.39, found C 36.03, H 5.91, N 9.30.

[C3-iso-C4iiii]PF, (123): 81% yield, 'H NMR (d^-acet): 8 0.96 (m, 9H), 1.99 (sept,

J=7.2 Hz, 2H), 2.24 (m, IH), 4.19 (d, J=7.3 Hz, 2H), 4.33 (t, J=7.2 Hz, 2H), 7.75 (m,

2H), 8.99 (s, IH). IR: 3161, 3117, 2969, 2881, 1566, 1472, 1166, 837, 557 cm ' Anal.

Calcd. for C,oHi9F6N2P: C 38.47, H 6.13, N 8.97, found C 38.52, H 6.21, N 8.94.

[C4-iso-C4iin]PF6 (124): 84% yield, 'H NMR (CDCI3): 8 0.95 (m, 9H), 1.34 (m,

2H), 1.85 (M, 2H), 2.15 (m, IH), 4.00 (d, J=7.3 Hz, 2H), 4.20 (t, J=7.2 Hz, 2H), 7.38 (m.

98 2H), 8.58 (s, IH). IR: 3161, 3117, 2966, 2938, 2878, 1565, 1471, 1165, 836, 558 cm"'.

Anal. Calcd. for C,,H2,F,N2P: C 40.49, H 6.49, N 8.59, found C 40.72, H 6.25, N 8.62.

[Cs-iso-C4iin]PF, (125): 90% yield, 'H NMR (CDCI3): 8 0.88 (t, J=7.1 Hz, 3H),

0.93 (d, J=6.7 Hz, 6H), 1.31 (m, 4H), 1.85 (pent, J=5.8 Hz, 2H), 2.17 (m, IH), 3.99 (d,

J=74 Hz, 2H), 4.17 (t, J=74 Hz, 2H), 7.35 (m, 2H), 8.54 (s, IH). IR: 3161, 3117, 2962,

2976, 1566, 1471, 1164, 832, 558 cm '. Anal. Calcd. for C,2H23F6N2P: C 42.35, H 6.81, N

8.23, found C 42.48, H 6.86, N 8.11.

[C5-iso-C4im]PF, (126): 96% yield, 'H NMR (CDCI3): 8 0.88 (m, 3H), 0.93 (d,

J=6.7 Hz, 6H), 1.30 (m, 6H), 1.92 (m, 2H), 2.17 (m, IH), 3.99 (d, J=7.4 Hz, 2H), 4.18 (t,

J=7.4 Hz, 2H), 7.36 (m, 2H), 8.54 (s, IH). IR: Anal. Calcd. for C13H25F6N2P: C 44.07, H

7.11, N 7.91, found C 44.31, H 7.39, N 7.95.

[C7-iso-C4im]PF, (127): 83% yield, 'H NMR (CDCI3): 8 0.86 (m, 3H), 0.94 (d,

J=6.7 Hz, 6H), 1.27 (m, 8H), 1.88 (m, 2H), 2.14 (m, IH), 3.99 (d, J=7.4 Hz, 2H), 4.17 (t,

J=74 Hz, 2H), 7.34 (m, 2H), 8.56 (s, IH). IR: 3164, 3120,2960, 2929,2859, 1569, 1471,

1168, 831, 557 cm'. Anal. Calcd. for C,4H2vF6N2P: C 46.65, H 7.39, N 7.61, found C

46.30, H 7.70, N 7.60.

[Cg-iso-C4im]PF, (128): 81% yield, 'H NMR (CDCI3): 8 0.86 (m, 3H), 0.94 (d,

J=6.7 Hz, 6H), 1.28 (m, lOH), 1.88 (m, 2H), 2.15 (m, IH), 3.99 (d, J=74 Hz, 2H), 4.18

(t, J=7.4Hz, 2H), 7.33 (m, 2H), 8.58 (s, IH). IR: 3160, 3117. 2959, 2929, 2858, 1565,

1469, 1163, 835, 557 cm'. Anal. Calcd. for C,5H29F6N2P: C 47.12, H 7.64, N 7.33, found

C 46.99, H 7.75, N 7.29.

[C<»-iso-C4im]PFs (129): 78% yield, 'H NMR (CDCI3): 8 0.88 (m, 3H), 0.93 (d,

J=6.7 Hz, 6H), 1.26 (m, 12H), 1.85 (m, 2H), 2.14 (m, IH), 4.01 (d, J=74 Hz, 2H), 4.20

(t, J=74 Hz, 2H), 7.31 (m, 2H), 8.89 (s, IH). IR: 3158, 3115, 2959, 2926, 2856, 1565,

99 1469, 1164, 837, 557 cm'. Anal. Calcd. for Ci.H^F.NoP: C 48.48, H 7.88, N 7.07, found C 48.01, H 7.79, N 7.21.

[C,o-iso-C4im]PF, (130): 83% yield, 'H NMR (CDCI3): 8 0.87 (m, 3H), 0.95 (d,

J=6.7 Hz, 6H), 1.26 (m, 14H), 1.88 (m, 2H), 2.14 (m, IH), 4.00 (d, J=74 Hz, 2H), 4.18

(t, J=74 Hz, 2H), 7.33 (m, 2H), 8.66 (s, IH). IR: 3159, 3116, 2959, 2926, 2855, 1565,

1469, 1164, 836, 557 cm'. Anal. Calcd. C„H33F6N2P: C 49.75, H 8.10, N 6.83, found C

50.00, H 8.26, N 6.92.

[iso-C5-mim]PF,(131): 85% yield, 'H NMR (d^-acet): 8 0.93 (d, J=6.5 Hz, 6H),

1.60 (m, IH), 1.79 (quart, J=6.9 Hz, 2H), 3.92 (s, 3H), 4.24 (t, J=7.5 Hz, 2H), 7.49 (t,

J=1.8 Hz, IH), 7.56 (t, J=1.8 Hz, IH), 8.64 (s, IH). IR: 3170, 3124, 2969, 1574, 1470,

1169, 836, 557 cm"'. Anal. Calcd. for CgH^FgN.P: C 36.25, H 5.75, N 9.39, found C

36.03, H 5.95, N 9.32.

[Cj-iso-CsimlPFs (132): 87% yield, 'H NMR (d^-acet): 8 0.97 (d, J=6.6 Hz, 6H),

1.57 (t, J=7.3 Hz, 3H), 1.66 (m, IH), 1.86 (m, 2H), 4.38 (quart, J=7.5 Hz, 2H), 7.78 (m,

2H), 9.05 (s, IH). IR: 3167, 3119, 2962, 2875,1576, 1470, 1165, 838, 557 cm'. Anal.

Calcd. for C,oH,9F6N2P: C 38.47, H 6.13, N 8.97, found C 38.59, H 5.84, N 9.16.

[Cj-iso-CsimlPF, (133): 81% yield, 'H NMR (d^-acet): 8 0.96 (m, 9H), 1.66 (m,

IH), 1.88 (m, 2H), 1.97 (quart, J=7.3 Hz, 2H), 4.32 (t, J=7.2 Hz, 2H), 4.37 (t, J=7.7 Hz,

2H), 7.75 (t, J=l .8 Hz, IH), 7.78 (t, J=l .8 Hz, IH), 9.02 (s, IH). IR: 3164, 3118, 2964,

2878, 1566, 1471, 1165, 836, 557 cm'. Anal. Calcd. for C,|H2,F6N2P: C 40.49, H 6.49, N

8.59, found C 40.39, H 6.52, N 8.51.

[C4-iso-C5im]PF5 (134): 85% yield, 'H NMR (CDCI3): 8 0.94 (m, 9H), 1.36 (m,

2H), 1.64 (m, IH), 1.81 (m, 4H), 4.18 (m, 4H), 7.34 (m, 2H), 8.56 (s, IH). IR: 3162,

100 3117, 2961, 2878, 1566, 1471, 1166, 837. 557 cm'. Anal. Calcd. for C,2H23F6N2P: C 42.35, H 6.81, N 8.23, found C 42.56, H 6.86, N 8.34.

[Cs-iso-CjiinlPF, (135): 89% yield, 'H NMR (CDCI3): 8 0.93 (m, 9H), 1.35 (m,

4H), 1.66 (m, IH), 1.87 (m, 4H), 4.35 (m, 4H), 7.74 (m, 2H), 8.98 (s, IH). IR: 3163,

3117, 2960, 2934, 2873, 1566, 1469, 1164, 836, 557 cm '. Anal. Calcd. for C,3H25F,N2P:

C 44.07, H 7.11, N 7.91, found C 44.38, H 7.11, N 7.97.

[C.-iso-CsimlPF, (136): 90% yield, 'H NMR (CDCI3): 8 0.85 (m, 3H), 0.95 (d,

J=6.6 Hz, 6H), 1.30 (m, 6H), 1.61 (m, IH), 1.82 (m, 4H), 4.17 (m, 4H), 7.33 (m, 2H),

8.59 (s, IH). IR: 3164,3118,2964,2878, 1566, 1471, 1165, 836, 557 cm'. Anal. Calcd. for C,4H27F,N2P: C 44.65, H 7.39, N 7.61, found C 45.97, H 7.29, N 7.74.

[C^-iso-CsimlPFj (137): 89% yield, 'H NMR (CDCI3): 8 0.85 (m, 3H), 0.95 (d,

J=6.6Hz, 6H), 1.29 (m, 8H), 1.61 (m, IH), 1.83 (m,4H),4.18 (m, 4H), 7.34 (m, 2H),

8.88 (s, IH). IR: 3159, 3116, 2958, 2930, 2859, 1561, 1163, 839, 557 cm'. Anal. Calcd. for C,5H29F6N2P: C 47.12, H 7.64, N 7.33, found C 49.08, H 7.86, N 7.69.

[Cg-iso-CsimlPFe. (138): 85% yield, 'H NMR (CDCI3): 8 0.85 (m, 3H), 0.95 (d,

J=6.6 Hz, 6H), 1.27 (m, lOH), 1.60 ( m, IH), 1.80 (m, 4H), 4.17 (m, 4H), 7.35 (m, 2H),

8.63 (s, 1H).IR: 3162,3117,2958,2929,2858, 1566, 1469, 1163, 836, 557 cm'. Anal.

Calcd. for C16H31F6N2P: C 4848, H 7.88, N 7.07, found C 48.60, H 8.04, N 7.32.

[C^-iso-CsimlPFs (139): 79% yield, 'H NMR (CDCI3): 8 0.87 (m, 3H), 0.95 (d,

J=6.6Hz, 6H), 1.27(m, 12H), 1.61 ( m, IH), 1.80 (m, 4H), 4.17 (m, 4H), 7.36 (m, 2H),

8.63 (s, 1H).IR: 3162,3117,2958,2927,2856, 1566, 1467, 1164, 838, 557 cm"'. Anal.

Calcd. for C,7H33F6N2P: C 49.75, H 8.10, N 6.83, found C 50.18, H 7.97, N 6.86.

[Cio-iso-CsimlPFs (140): 85% yield, 'H NMR (CDCI3): 8 0.87 (m, 3H), 0.95 (d,

J=6.6Hz, 6H), 1.27 (m, 14H), 1.61 ( m, IH), 1.80 (m, 4H), 4.17 (m, 4H), 7.31 (m, 2H),

101 8.62 (s, IH). IR: 3161,3117, 2957, 2926, 2856, 1566, 1468, 1164, 839, 557 cm'. Anal.

Calcd. for C,9H,5F,N2P: C 50.93, H 8.31, N 6.60, found C 51.22, H 8.26, N 6.69.

3.7.6. Preparation of Symmetric 1.3-Dialkylimidazolium Hexafluorophosphate Ionic Liquids

Ionic liquids 104, 113, 141-148 were prepared according to developed in this research procedures from the corresponding by 1,3-dialkylimidazolium halides by a metathesis reaction with KPF^.'" The ionic liquids gave spectroscopic and combustion analysis consistent with the proposed structures.

3.7.7. Preparation of Ionic Liquids 155-157 Containing Functional Groups

LiN(S02CF3)2 was added to an equimolar amount of l-X-3-alkylimidazolium bromide or iodide dissolved in distilled, deionized water. The mixture was allowed to stir for 30-40 min until phase separation took place. The aqueous layer was decanted and the organic layer dissolved in dichloromethane, followed by two-three extensive washings with distilled, deionized water. Dichloromethane was evaporated in vacuo and the resulting ionic liquid was dried under 0.15 Torr vacuum at 70-100 °C.

[CH30(CH2)2-mim]NTf2 (155) was prepared in 95% yield, Tg= -81 °C. 'H NMR

(d^-acet) 8: 3.35 (s, 3H), 3.81 (t, J=5.0Hz, 2H), 4.08 (s, 3H), 4.53 (t, J=4.8Hz, 2H), 7.70

(t, J=l .8Hz, IH), 7.73 (t, J=l .8Hz, IH), 9.00 (s, IH). IR 3159, 3122,2943, 2903, 1567,

1454,1351, 1189, 1056, 616 cm"'. Anal. Calcd. for C9H,3F6N305S2: C 25.66, H 3.11, N

9.97, O 18.99, found C 25.23, H 3.09, N 9.87.

[HO(CH2)2-mim]NTf2 (156) was prepared in 90% yield, Tg= -79 °C. 'H NMR

(dfi-acet) 8: 3.98 (t, J=5.0Hz, 2H), 4.07 (s, 3H), 4.13 (s, IH), 4.44 (t, J=5.0Hz, 2H), 7.69

102 (t, J=l .7Hz, IH), 7.74 (t, J=l .7Hz, IH), 8.99 (s, IH). IR 3545, 3160, 3122, 2965, 1575,

1452, 1352, 1198, 1057, 616 cm'. Anal. Calcd. for C8H,,F6N305S2: C 23.59, H 2.72, N,

10.32, found C 23.48, H 2.84, N 10.21.

[C6F,3(CH2)2-mim]NTf2 (157) was prepared in 87% yield as an oil. 'H NMR (d^- acet) 6: 3.11 (m, 2H), 4.09 (s, 3H), 4.85 (t, J=7.0Hz, 2H), 7.77 (t, J=l .8Hz, IH), 7.94 (t,

J=l .8Hz, IH), 9.20 (s, IH). "F NMR (d^-acet) 8: -79.63 (m, 6F), -81.35 (m, 3F), -114.10

(m, 2F), -122.05 (m, 2F), -123.06 (m, 2F), -123.78 (m, 2F), -126.22 (m, 2F).

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20.P. Wasserscheid, CM. Gordon, C. Hilgers, M. J. Muldoon, 1. R. Dunkin, Chem. Commun. 2001, 1186.

21.M. J. Muldoon, CM. Gordon, I. R. Dunkin, J. Chem. Soc, Perkin Trans. 2 2001, 433.

22. (a) D. W. Armstrong, L.-K. Zhang, L. He, M. L. Gross, Anal. Chem. 2001, 73, 3679; (b) A. E. Visser, R. P. Swatloski, W. M. Reichert, R. Mayton, S. Sheff, A. Wierzbicki, J. H. Davis, Jr., R. D. Rogers, Chem. Commun. 2001,135.

23. C Reichardt, Chem. Rev. 1994, 94, 2319.

24. J. F. Deye, T. A.Berger, A. G. Anderson, Anal. Chem. 1990, 62,615.

25. S. M. Paley, J. M. Harris,7. Org. Chem. 1991, 56, 568.

104 CHAPTER IV

SPECTROSCOPIC STUDIES ON IONIC LIQUIDS

4.1. Nuclear Magnetic Resonance (NMR) Spectroscopy of Ionic Liquids

NMR spectroscopy is an estabUshed technique for studying various ir-complexes and hydrogen-bonding systems.' Both types of interactions are present in ionic liquids.

Therefore, NMR spectroscopy is an appropriate experimental method to study interactions between an imidazolium cation and anion. Most of the earlier studies probed ionic interactions in chloroaluminate ionic liquids.^ NMR spectroscopy was also shown to be a convenient tool for determining the composition of chloroaluminate melts.'

Later, chemical shifts of imidazolium protons in air- and water-stable room- temperature ionic liquids were determined by 'H NMR spectroscopy." It was found that chemical shifts of the imidazolium protons (Figure 4.1) depend on both the anion and

M(2)

H3C--Kj-y--^ M-CnH2n+i

(4)H H(5)

Figure 4.1. Assignment of imidazolium protons in an 1 -alkyl-3-methylimidazolium cation. concentration. This effect is more pronounced for the H(2) imidazolium proton than for the H(4) and H(5) protons.

At present, there is limited information in the literature about the NMR spectroscopic behavior of ionic liquids." For this reason, several aspects of NMR

105 spectroscopy of ionic liquids were addressed in this research. This information helps in understanding the nature of interactions present in ionic liquids and provides knowledge for the rational design of such solvents. Since the chemical shifts of the imidazolium protons H(2), H(4) and H(5) are most influenced by such variables as the concentration, structure of the ionic liquid, nature of the deuterated solvent and temperature, only their behavior is described in this dissertation.

4.1.1. Influence of the Nature of Deuterated Molecular Solvents on the Chemical Shifts of Imidazolium-Containing Ionic Liquids

The ionic interactions present in neat ionic liquids will be affected by the addition of molecular solvents. Depending on the dielectric constants of the molecular solvents, more or less effective ion solvation should be observed, leading to changes in the NMR spectra of the ionic liquid.^ In agreement, the formation of solvent-separated ion pairs in d6.DMSO and tight ion pairs in CDCI3 was postulated for the [C4-mim]BPh4 salt.' Also, for this reason, the chemical shifts of imidazolium protons are much more sensitive to concentration effects in CDCI3 than in d^-DMSO.

In this research, the influence of CDCI3, d^-acetone and d^-DMSO on chemical shifts of ionic liquids was investigated further. It was found that the NMR behavior of imidazolium protons of ionic liquids in d^-acetone is similar to that in dg-DMSO.

Therefore, the more practically useful dg-acetone can be used to study ion-solvent interactions. On the other hand, CDCI3 is an attractive solvent to gain insight into the ion-ion interactions.

106 4.1.2. Relative Assignment of the H(4V and Hr5V Imidazolium Protons

Assignment of the H(4)- and H(5)-imidazolium protons (Figure 4.1) in [C2- mim]AlCl4 ionic liquid was accomplished by NOE experiments.* Without specifying the solvent, the H(4) proton was assigned to the upfield signal and the H(5) proton to the downfield absorption. By analogy, this identification of these two protons was extended to other ionic liquids.^'* However, the sensitivity of chemical shifts of imidazolium protons to concentration, identity of anions and the nature of deuterated solvents, among other factors, suggests that the relative assignment of H(4) and H(5) protons should receive a more thorough examination.

Recentiy, the NMR spectroscopic behavior of [C4-mim]PF6, and [C4-mim]BF4 and ionic liquids in a number of deuterated and non-hydrogen containing solvents was reported.* Based on the NMR data and theoretical calculations, it was found that molecular solvents have similar effects on both the H(4)- and H(5)-imidazolium protons.

However, the relative assignments of these protons was not addressed.

Non-hygroscopic [Cg-mimlPF^ (88) ionic liquid was chosen as a model compound to investigate the influence of deuterated solvent, concentration and temperature on the relative positions of the H(4)- and H(5)-imidazolium protons. The choice of this imidazolium salt was done to assure solubility of the ionic liquid in all of the deuterated solvents. Furthermore, the influence of anion and structure of the cation on the positions of H(4) and H(5) protons was investigated. Differentiation between the H(4) and H(5) protons can be accomplished easily by NOESY ID NMR experiments.' The presence of peaks in NOESY ID NMR specti-a upon irradiation of specific protons suggests that there is a correlation between these protons. If such a correlation is absent, no peaks would be

107 observed. Therefore, irradiation of spacially closest protons, such as NCH3 and/or NCHj, allows an unambiguous assignment of the H(4) and H(5) protons.

4.1.2.1. Influence of the Nature of Deuterated Solvent

NOESY ID NMR experiments of ionic liquid 88 in three deuterated solvents were performed and results are shown in Table 4.1. By irradiation of the NCH3 protons

Table 4.1. Influence of the deuterated solvents on the chemical shifts in ppm of the H(4)- and H(5)-imidazolium protons of [Cg-mimJPFfi (88) ionic liquid. Solvent H(4) H(5)

CDCI3 7.29 7.25

dfi-acetone 7.72 7.78

d^-DMSO 7.69 7.76

the downfield peak was assigned to the H(4) imidazolium proton and the upfield peak to

H(5). However, in d^-acetone, the downfield signal is assigned to the H(5) proton and the upfield signal to H(4). In d^-DMSO, the relative positions for these imidazolium protons was the same as in dg-acetone. This is a fu-st demonstration that the position of the H(4)- and H(5)-imidazolium protons is solvent dependent. This should be taken into account in the assignment of chemical shifts for these protons. Also, the literature data should be revisited.

4.1.2.2. Influence of Concentration on the Relative Positions of the H(4)- and H(5)-Imidazolium Protons It is a known that the chemical shift displacement with changes in concentration depends on hydrogen bonding and leads to upfield shifts, while Jt-stacking produces a

108 downfield shift." The influence of concentiation was probed by recording NOESY ID

NMR spectra of ionic liquid 88 as 0.05 and 2 M solutions in the three deuterated solvents.

No concentration dependence was noted in d^-acetone and d^-DMSO. For the 2 M solution in CDCI3, the H(4) and H(5) protons appeared as a singlet. Therefore, the concentration was lowered. Separation of H(4) and H(5) signals was achieved at a much lower concentration of 0.05 M. For this reason, at present, the concentration dependence in CDCI3 cannot be unambiguously established.

4.1.2.3. Influence of Temperature on the Relative Positions of the H(4) and H(5) Protons

A range of temperatures (-25, 25 and 50 "C) was utilized to establish the effect of temperature on the relative positions of the two imidazolium protons of ionic liquid 88.

Both 0.05 and 2 M solutions of ionic liquid 88 in dg-DMSO froze at this temperature, so data could not be collected. At higher temperature (50 °C), the ionic liquid in dg-acetone did not give a stable signal, excluding this sample from consideration. The samples in

CDCI3 and dg-acetone did not freeze at -25 °C. Also, in CDCI3, a stable signal at 50 °C was obtained. Therefore, the relative positions of the H(4) and H(5) protons with respect to temperature are made based on the data obtained in CDCI3. The relative position of

H(4) and H(5) imidazolium protons appeared to be temperature independent in CDCI3.

4.1.2.4. Influence of the Anion on the Relative Positions of of the H(4)- and H(5)-Imidazolium Protons

To establish the anion influence on the chemical shifts of the imidazolium protons, several ionic liquids were considered (Table 4.2). The anions, acetate (159),

109 Table 4.2. Anion influence on the chemical shifts in ppm of imidazolium protons of [Cg-mim]X ionic liquids as 0.50 M solutions in CDCI3. Compound X H(4) H(5)

88 PF6 7.32 7.30 158 Br 7.76 7.57

159 CH3CO2 7.44 7.33

160 B(C6H5)4 5.53 5.73

bromide (158), hexafluorophosphate (88) and tetraphenylborate (160), were chosen to

have different electronic and steric properties. For ionic liquids 88,158 and 159, the

H(4) and H(5) protons appeared as downfield and upfield signals, respectively. A reverse

order for these imidazolium protons signals was observed for ionic liquid 160. Such

different behavior is likely to be due to specific interactions observed in BPh4"-

containing ionic liquids, which are absent in other ionic liquids.

An interesting fact regarding the position of the anion relative to the cation was

noted in the case of [Cg-mim]CH3C02 (159) ionic liquid from a NOESY ID NMR

specti^m at a concentration 0.5 M in CDCI3. By irradiating the CH3-group of the

CH3C02~, weak correlations with the H(4)- and NCH3-imidazolium protons were

observed. This suggests positioning the acetate anion relative to imidazolium cations as

shown in Figure 4.2. Although both arrangements are possible, it is likely that at lower

concentrations structure V would be the preferred.

110 ^*>C O© CH3

'^^.>^^. ^N ^0<^CH3 ,©\^^ H'^N.C3H,, H3C

V VI Figure 4.2. Possible modes of anion - cation interaction in [Cg-mim]CH3C02 (159) ionic liquid with correlations shown by arrows.

4.1.2.5. Influence of the Structure of Imidazolium Cation Structure on the Relative Positions of the H(4)- and H(5)- Imidazolium Protons

The 1-alky 1-3-alkyr-imidazolium ionic liquids of [Cg-mimJPFj (88), [Cg-

CjimJPFg (110) and [C8-C3im]PF6 (118) were utilized to establish the effect of structural variations in the imidazolium caton on the relative positions of the H(4)- and H(5)- imidazolium protons. For all three ionic liquids, the downfield signal was attributed to

H(5) and the upfield absorption to H(4). Thus, this level of structural variation within the imidazolium cation was insufficient to alter the relative positions of the imidazolium protons. Aralkyl substituents were introduced into the imidazolium cation to give

[C6H5(CH2)„-mim]PF6 ionic liquids 149-151. As revealed by the NOESY ID spectra of these compounds in d^-acetone, the relative positions of the imidazolium protons remained unchanged. The introduction of bulkier benzhydryl-goups in [(C6H5)2CH- mim]Cl (13) ionic liquid was expected to have a greater impact. However, the relative positions of the H(4) and H(5) imidazolium protons in ionic liquid 13 were the same as those in ionic liquids 88,110,118 and 149-151.

Collectively, these results demonstrate for the furst time that the relative positions for the H(4)- and H(5)-imidazolium protons is subject to deuterated solvent and anion

111 effects only. The correlations are general. Therefore, the assignment of these protons in various ionic liquids is now possible.

4.1.3. Influence of the Anion on the Chemical Shifts of the H(2VImidazolium Proton

Hydrogen bonding is expected to produce a downfield proton shift." Since the

H(2)-imidazolium proton experiences the strongest interaction with the anion, the behavior of this proton was investigated exclusively for various l-octyl-3- methylimidazolium ionic liquids (Figure 4.3). In general, a more basic anion caused

Table 4.3. Chemical shifts in ppm for the H(2)-imidazolium proton of [Cg-mim]X ionic liquids as 0.10 M solutions in CDCI3 at 25 °C. Compound X 0.10 M

160 B(C6H5)4 4.62

88 PFe 8.47

101 N(S02CF3)2 8.74

161 BF4 9.11

162 NO3 9.94

163 CF3CO2 10.31

158 Br 10.49

159 CH3CO2 11.78 greater downfield shift for imidazolium-ring protons. Based on these data, relative basicities of anions can be established. The PFg^is the least basic anion in the series.

The upfield shift for H(2) imidazolium proton in [Cg-mim]B(C6H5)4 (160) ionic liquid is

112 in agreement with literature data,' and is attributed to pointing of this proton to the center of one of the phenyl rings of the anion.

4.1.4. Influence of Concentration on the Chemical Shift of the Imidazolium Protons in Different Ionic Liquids

The influence of concentration on the chemical shifts of imidazolium protons is fairly complex." It is expected that as the concentration increases dominant ion-solvent interactions will be replaced by ion-ion interactions. The ion-ion interactions can be described in terms of both cation-cation and anion-cation interactions. As the concentration of an ionic liquid increases, the anion-cation interactions will be enhanced through hydrogen bonding. This should be reflected in the downfield shift for the imidazolium protons." On the other hand, two imidazolium cations will come in closer proximity as the concentration increases. This ring-stacking should lead to upfield shifts for the imidazolium cation protons, since they enter the electronic currents of n-orbitals of the neighboring imidazolium cation. The overall picture can be described as follows: at low concentrations, anion-cation infractions are dominant in a low-solvating solvent, such as CDCI3. For this reason, the interactions are governed by hydrogen-bonding. As the concentration increases, cation-cation interactions become dominate over anion- cation interactions. Then, jt-interactions become responsible for the proton signal shifts.

In this research, the influence of concentration on the chemical shifts of imidazolium cation protons was studied. A concentration range between 0.01 and 1 M was utilized. The lower limit was determined by the practical reason of needing to acquire the NMR spectra in a reasonable amount of time. At concentiations above 1 M, broadened of signals were observed. So those concentration were not considered.

113 Results for the behavior the H(2)-imidazolium proton chemical shift as a function of concentration for a set of [Cg-mim]X ionic liquids are summarized in Table 4.4.

Table 4.4. Dependence of chemical shifts in ppm for H(2) imidazolium proton on the concentration of [Cg-mim]X ionic liquids as solutions in CDCI3 at 25 °C. Compound X 0.01 M 0.10 M 0.50 M LOOM

160 B(C,H5)4 4.82 4.62 4.58 4.60

88 PFe 8.61 8.47 8.45 8.44

101 N(S02CF3)2 8.90 8.74 8.69 8.68

161 BF4 9.67 9.11 9.07 9.08

162 NO3 9.96 9.94 9.84 9.81

163 CF3CO2 10.76 10.31 10.12 10.04

158 Br 10.80 10.49 10.25 10.29

159 CH3CO2 12.05 11.78 11.42 11.23

As can be seen from the data, an increase in the concentration produces an upfield shift for the H(2) proton. The more significant changes take place in the 0.01 to 0.50 M range.

Apparently, cation-cation interactions have the greatest influence at this range of concenti-ations forcing away the anion. Above 0.50 M, some of the anions come closer to the cations leading to slight downfield shift.

The influence of concenti-ation on the H(4) and H(5) protons was reported to be different from that of the H(2) imidazolium proton." In case of basic anions, such as

CH3CO2" and CF3CO2", a downfield shift for the H(4) proton was observed with an increase of concentiration. The H(5) proton behaved similarly. An upfield shift for this proton in [C2-mim]NTf2 and [C2-mim]OTf ionic liquids was attributed to the inert nature

114 of NTfj and OTf anions." It should be mentioned that those results were obtained from 'H NMR spectra measured in d^-acetone. Therefore, they are unlikely to represent true ion-ion interactions.

In this research, the choice of imidazolium cation was made so as to assure that all of the ionic liquids would be soluble in CDCI3, in which ion-ion interactions will be less obscured by ion-solvent interactions. Since the behavior of the H(4) imidazolium proton is similar to that of the H(5) proton in CDCI3, only one of these protons will be described.

The behavior of the H(4) proton with respect to concentration in several ionic liquids is shown in Table 4.5. It is readily apparent that the principles influencing this proton in

Table 4.5. Dependence of chemical shifts in ppm for H(4) imidazolium proton on the concentration of [Cg-mimJX ionic liquids as solutions in CDCI3 at 25 °C. Compound X 0.01 M 0.10 M 0.50 M LOOM

160 B(C,U,), 6.08 5.66 5.53 5.51

88 PF6 7.25 7.30 7.32 7.32

101 N(S02CF3)2 7.25 7.32 7.35 7.36

161 BF4 7.28 7.42 7.49 7.50

162 NO3 748 7.49 7.61 7.65

163 CF3CO2 7.18 7.40 7.56 7.61

158 Br 7.27 7.61 7.76 7.83

159 CH3CO2 7.07 7.18 7.44 7.60

CDCI3 are completely different from those reported earlier for the proton in dg-acetone."

The downfield shift for this proton for all ionic liquids except [C8-mim]B(C6H5)4 (160) suggests that the H(4) protons become more involved in hydrogen-bonding with the

115 anion, as the concenti-ation increases. This correlates well with the behavior of the H(2)- imidazolium proton as a function of concentration. In other words, as the anion comes into closer proximity to the H(4) proton it lessens the interaction with the H(2) proton.

This explanation correlates well with an upfield shift for the H(4) proton in the case of ionic liquid 160, since now the H(4) proton will be pointing toward one of the phenyl rings of the anion.

4.1.5. Influence of Elongation of the Alkvl Substituent (C^) in rC-C„im1PF. with n = 1-4 (88.110.118.164) and KCJI.),CH-C„imlNTL with n = 1-4 (165-168) Ionic Liquids on the Chemical Shifts of the H(2)-. H(4)- and H(5)- Imidazolium Protons

The influence of the length of the alkyl chain length on the 'H NMR chemical shifts of imidazolium ring protons was studied for ionic liquids 88,110,118,164 and

165-168 in CDCI3. Results for the H(2)-imidazolium protons in [Cg-C„im]PF6 ionic liquids 88,110,118 and 164 are presented in Table 4.6. Apparentiy, as the alkyl group is elongated, stability of the carbene-like structure (Figure 4.3) of the ionic liquid is

Table 4.6. Alkyl group influence on the 'H NMR chemical shifts (in ppm) of the H(2) proton of [Cg-Cnim]PFfi ionic liquid as 0.10 M solutions in CDCI3. Compound n H(2)

88 1 8.47

110 2 8.57

118 3 8.61

164 4 8.59

116 enhanced. This makes the H(2) proton more available for the hydrogen-bonding with the anion, which leads to the downfield shift.

H H® 1^ •• C8Hi7-N<^N-^n'^2n+1 C8Hi7-,^/^K|-CnH2n+i \^ \=J Figure 4.3. Possible resonance structures of [Cg-C„im]PF6 ionic liquids.

Furthermore, if a carbene-like resonance structure of the ionic liquid is viable, similar and even greater effects should be observed for the [(C6H5)2CH-C„im]NTf2 ionic liquids. The bulkier benzhydryl-group, (C6H5)2CH, should have a greater stabilizing effect on the

"carbene" than the octyl group in the 88,110,118 and 164 ionic liquids.

This assumption is supported by trend in the chemical shifts for the H(2)- imidazolium protons in the series of ionic liquids 165-168 shown in Table 4.7.

Interestingly, the stabilization effects of the ethyl and propyl groups are fairly similar.

Table 4.7. Chemical shifts (in ppm) of the H(2) proton as a function of the alkyl group in [(C6H5)2CH-C„im]NTf2 ionic liquids as determined by 'H NMR spectroscopy at 0.10 M solutions in CDCI3. Compound n H(2)

165 1 848

166 2 8.61

167 3 8.62

168 4 8.80

117 affording almost identical chemical shifts. Notable effects are observed for changes from methyl to ethyl in 165 and 166, and from propyl to butyl in 167 and 168 ionic liquids.

Elongation of the alkyl group was found to have no significant effect on the chemical shifts of the H(4)- and H(5)-imidazolium protons in either the [Cg-C„im]PF6 or

[(C6H5)2CH-C„im]NTf2 ionic liquids.

These results are of importance for metal-assisted reactions in ionic liquids, which are believed to involve imidazolium carbene-like species.' Based on these data, rational design of ionic liquids can be achieved to afford more efficient solvents for various coupling reactions.

4.1.6. Influence of Temperature on the Chemical Shifts of fCg-mimlPF^ (88) Ionic Liquid

In this research, the influence of temperature on imidazolium protons of [Cg- mimJPFg (88) ionic liquid was also investigated. The results are given in Table 4.8. At

Table 4.8. Chemical shifts of the H(2)-. H(4)- and H(5)-imidazolium protons in [Cg-mimJPFg (88) ionic liquid as a function of temperature at -25 °C / 25 °C / 50 °C at 2 and 0.05 M concentrations (in parentheses) as determined by 'H NMR spectroscopy. Solvent (cone. M) H(2) H(4) H(5)

CDCl3(2) 8.45/8.43/8.43 7.36/7.34/7.32 7.36/7.34/7.32

CDCl3(0.05) 8.49/8.49/8.48 7.32/7.29/7.27 7.29/7.25/7.24

dfi-acetone (2) 8.85/8.79/8.75 7.64/7.59/7.56 7.71/7.66/7.63

dft-acetone (0.05) 9.08/9.00/8.99 7.78/7.72/7.68 7.85/7.78/7.74

d6-DMSO(2) -/9.04/8.99 -/7.63/7.60 -/7.70/7.66

dg-DMSO (0.05) -/9.08/9.05 -/7.69/7.66 -/7.76/7.73

118 -25 °C, the sample in d^-DMSO froze, so no data could be collected. The effect of temperature was greater for samples in d^-acetone and d^-DMSO. In all cases, an upfield shift is noted as the temperature increases. Apparently, with higher temperature, cation- cation interactions are enhanced. Also, at higher concentration (2 M), the temperature change has a greater impact on the chemical shifts of these protons. This is understandable, since the ion pairs are in closer proximity to each other and any reorganization would cause more notable changes than at lower concentration, where the ion pairs are separated further by solvent molecules.

4.1.7. Influence of Concentration and Solvent on Anions of Several Ionic Liquids

Spectroscopic behavior of the anion in ionic liquids has received very littie attention. Multinuclear NMR spectroscopy, such as CI and Al NMR,'" was applied to obtain insight into anion behavior for haloaluminate-containing ionic liquids. 'H NMR chemical shifts of the protons of "B(C6H5)4 in [C4-mim]B(C6H5)4 ionic liquid were shown to be insensitive to concentration.' In this research, ionic liquids containing different anions were utilized to get an idea of how the anion behaves with respect to the concentration and solvent. The choice of the anion was based on practical considerations for acquiring NMR spectra. For this reason, CH3CO2", CF3CO2" and "N(S02CF3)2- containing ionic liquids, which can be rapidly studied by 'H or "F NMR spectroscopy, were selected.

119 4.1.7.1. Influence of Concentration and Solvent on the 'H NMR Chemical Shifts of CH3CO2" in [C8-mim]CH3C02 (159) Ionic Liquid

The methyl group in the acetyl anion provides insight into the behavior of the anion as shown in Table 4.9. Small observed changes in chemical shifts are likely to

Table 4.9. Influence of concentration and solvent on the chemical shifts (in ppm) of CH3CO2" in [Cg-mim]CH3C02 (159) ionic liquid as determined by 'H NMR spectroscopy. Solvent 0.01 M O.IOM 0.50 M LOOM

CDCI3 2.03 2.02 2.00 1.98

dg-acetone 1.73 1.73 1.74 1.75

indicate that methyl group of the anion is remote from the imidazolium cation. In agreement with previous observations, smaller changes were observed in the more solvating dfi-acetone, than in the less solvating CDCI3. A downfield shift for the methyl group protons in CDCI3 correlates with weakening of the hydrogen bonding interaction between the H(2)-imidazolium proton and the anion as the concentration increases.

However, the concentration has litfle overall effect on the acetyl anion in [Cg- mim]CH3C02 ionic liquid.

4.1.7.2. Influence of Concenti-ation and Solvent on "F NMR Chemical Shifts of-N(S02CF3)2 and CF3CO2- in [Cg-mim]NTf2 (101) and [Cg-mimJCFjCOz (163) Ionic Liquids. '^ NMR chemical shifts for the fluorine-containing anions are presented in Table

4.10. Several differences are evident immediately. The solvent has a significant

120 Table 4.10. Influence of solvent and concentration on the fluorine chemical shifts (in ppm) of [Cg-mim]N(S02CF3)2 and [C8-mim]CF3C02 ionic liquid as determined by '^ NMR spectroscopy. Solvent 0.01 M O.IOM 0.50 M LOOM

[Cg-mim]NTf2

CDCI3 -79.53 -79.66 -79.72 -79.78

dfi-acetone -79.77 -79.76 -79.73 -79.72

[Cg-mim]CF3C02

CDCI3 -75.83 -75.60 -75.54 -75.49

dg-acetone -74.68 -74.77 -74.79 -74.79

influence on the chemical shifts of these anions. This is not surprising, since similar behavior was noted in the 'H NMR absorptions for the imidazolium protons.

Concentration also has a different effect on these anions. An upfield shift for

"N(S02CF3)2 anion is noted in CDCI3; whereas a downfield shift is observed in d^- acetone. An opposite trend is noted for the CF3C02~-containing ionic liquid. This effect is likely to be due to the differences in the electi-onic and structural features of the anions in [Cg-mimJNTfj (101) and [C8-mim]CF3C02(163) ionic liquids. Obviously, more detailed studies will be required to fully understand the observed trends. Also, in agreement with previous observations, greater changes are observed in low coordinating

CDCI3.

4.2. Intermolecular Dvnamics of Room-Temperature Tonic Liquids

The vast majority of studies on stiiictural aspects of the ionic liquids deal with macromolecular properties (or also known as bulk properties) of these solvents. Certain

121 conclusions about the nature of interactions within ionic liquids can be drawn based on the data obtained from investigation of these bulk properties. However, it is important to study the behavior at the micromolecular level as well. Combined information about macro- and micromolecular properties can lead to a comprehensive understanding of the nature of these novel and intriguing ionic solvents.

As a collaborative effort with the Quitevis Research Goup, the first direct measurement of the ultrafast dynamics of the ionic liquids by optical heterodyne-detected

Raman-Induced Kerr Effect Spectroscopy (OHD-RIKES) was performed. Femtosecond dynamic optical Kerr effect studies provide information about interactions within the liquids on the molecular level." There is no other convenient and reliable technique available that could provide a similar information.

In this initial study, the effect of varying the length of the alkyl chain and the substituent on the imidazolium cation on the ultrafast dynamics associated with the intermolecular modes in [C„-mim]NTf2 ionic liquids 95, 97, 98, 99,101,103 was determined. Due to the complexity of these spectroscopic measurements not all members of a consecutive series of the ionic liquids were utilized. Only those ionic liquids that gave stable low-noise signals were considered.

All of the studied ionic liquids possess similarities in the intramolecular dynamics properties. Based on these data, it is also possible to estimate the relative strength of the anion-cation interactions. According to their spectoscopic properties, the ionic liquids can be split into three groups. [C2-mim]NTf2 (95) ionic liquid exhibited a considerably longer diffusive relaxation time compared to the other ionic liquids. [C4-mim]NTf2 (97),

[C5-mim]NTf2 (98) and [Cg-mimlNTfj (99) ionic liquids showed coherent oscillation in

OHD-RIKES transients. This phenomenon is known for small molecules liquids.

122 Usually these oscillations are assigned to intramolecular vibrational modes of the molecules. However, because these peaks are not observed in all other ionic liquids, they were attributed to an intermolecular vibrational mode.

As can be seen from the data presented on Figure 4.4, the relaxation times

2 1

Normalized signal 1.5 103 101 0.9 99 98 0.3 97 95 Time delay (ps)

Figure 44. Normalized OHD-RIKES signals of [C„-mim]NTf2 ionic liquids.

decrease as the alkyl chain is lengthen. For the [C,o-mim]NTf2 (103) ionic liquid, there is

essentially no relaxation present, so the signal is entirely electronic. Such response

would be expected for a solid compound. It is apparent that there is an increase in the

solid-like character of the ionic liquid with the elongation of the alkyl chain. However,

[C,o-mim]NTf2 (103) ionic liquid is a free-flowing liquid. Thus this example illustrates

the existence of the ordered structure in the liquids. The major contributor to this type of ordering seems to be the interactions of the imidazolium cations, i.e., cation-cation interactions.

123 From these data, it might be possible to differentiate the contributions of the cation-cation and anion-cation interactions and their influence on the physical properties of ionic liquids.

Cation-cation interactions, which are responsible for observed trends in densities, viscosities, etc., within a particular set of ionic liquids, also seem to control the local structure of the ionic liquids. The anion-cation interactions, apparently, contribute more to the magnitude of the bulk properties of the liquids. This is reflected in the fact that major impact they have on the phase transition temperatures of the ionic liquids. For example, [C,o-mim]NTf2 (103) is a liquid, whereas [Cio-mimJPFg (94) is a low-melting solid.

Thus, by the use of the femtosecond dynamics technique, the experimental estimation of the influence of the cation-cation on the physical properties of the ionic liquids is now possible. These intereactions control the micro-properties of ionic liquids.

This has an implication in the design of ordered solvents and for their potential applications in a number of synthetic applications, where an ordered transition state is involved.

4.3. Conclusions

NMR spectroscopic studies on various ionic liquids were performed. The factors that influence the chemical shift behavior of imidazolium protons were investigated.

Specific trends in changes of chemical shifts of imidazolium-ring protons were determined by studying series of structurally related ionic liquids. Also, the behavior of

ionic liquid anions was investigated.

124 Intermolecular dynamics studies of a series of room-temperature ionic liquids [C„- mim]NTf2 were performed. Information gained allowed for stipulation of contributions by cation-cation and anion-cation interactions on the molecular level. For the first time, experimental evidence on the micromolecular level was provided, showing that an increase of ordering of the imidazolium cation structure is due to the elongation of the alkyl chain of the substituents on the imidazolium cation in ionic liquids.

4.4. Experimental section

4.4.1. Materials

For synthesis of the ionic liquids, commercially available, reagent-grade starting materials from Acros, Aldrich or 3M company were used as received. Deuterated solvents were dried and stored over 4 A molecular sieves. Ionic liquids were prepared according to literature procedures and gave spectroscopic and combustion analysis consistent with the proposed structures.'^

4.4.2. Physical and analytical methods

The 'H NMR spectra were recorded on Brucker AF-200, Bruker AF-300 or

Varian Unity INOVA 500 spectrometers at 25 "C in CDCI3 or dg-acetone and chemical shits are reported downfield from TMS. "F NMR spectra were recorded on a Varian

Unity INOVA 500 spectrometer at 25 °C in dg-acetone or CDCI3 with CF3COOH as the external standard. NOESY ID NMR experiments were performed on a Varian Unity

INOVA 500 specti-ometer at 25 "C Multiplicities are abbreviated as s = singlet, t = tiiplet, quart = quartet, quint = quintet, sept = septet and m = multiplet. IR spectra were recorded with a Perkin Elmer Model 1600 infrared spectrometer as films for oil and

125 liquid samples or by deposits on a NaCl plate from dichloromethane or methanol solutions for solid samples. Melting points were obtained with a Mel-Temp melting point apparatus. Combustion analysis was performed by Desert Analytics Laboratory of

Tucson, Arizona. Apparatus for the OHD-RIKES experiments is in literature."

44.3. Preparation of lCa-mimlR(C^H.)^ (160) and [Cg-mim1BF^ (161) Ionic Liquids

A sodium salt (NaB(C6H5)4 or NaBF4) was added to an equimolar amount of [Cg- mim]Br dissolved in water. The reaction mixture was stirred for 30-40 min at room temperature, before being extracted with dichloromethane. Removal of the dichloromethane in vacuo gave the desired product, which was dried under vacuum at

0.15 Torr at 70-100 °C.

[C8-mim]B(C6H5)4 (160) was obtained in 91% yield as a solid with mp 96 "C. 'H

NMR (dg-acetone): 8 0.87 (m, 3H), 1.29 (m, lOH), 1.88 (m, 2H), 3.80 (s, 3H), 4.13 (t,

J=74 Hz, 2H), 6.78 (m, 4H), 6.94 (m, 8H), 7.09 (t, J=l .6 Hz, IH), 7.19 (t, J=l .6 Hz, IH),

7.39 (m, 8H), 7.49 (s, IH). IR: 3122, 3054, 2998, 2984, 1578, 1543, 1479, 453, 1426,

1145,909,733,706 cm'.

[C8-miin]BF4 (161) was obtained in 92 % yield as a liquid.'' 'H NMR (CDCI3): 8

0.86 (t, J=64 Hz, 3H), 1.29 (m, lOH), 1.88 (m, 2H), 3.98 (s, 3H), 4.21 (t, J=7.3 Hz), 7.46

(t, J=1.6 Hz, IH), 7.51 (t, J=1.6 Hz, IH), 7.42 (m, 6H), 9.04 (s, IH). IR 3158, 3119,

2926,2856,1573,1467,1170,1058,754 cm-'.

126 444. Preparation of fCg-mimlCH^^CO. (159). ICg-mimlNO, (162) and ICs-mimlCF^CO-, (163) Ionic Liquids

A silver salt (AgCH3C02, AgN03 or AgCF3C02) was added to an equimolar

amount of [Cg-mim]Br dissolved in methanol. Formation of precipitate was noted

immediately. The reaction mixture was placed into an ice bath and stirred for 30-40 min,

and filtered. The methanol was evaporated in vacuo. The residue was redissolved in

acetone and filtered twice to obtain a clear solution. Removal of the methanol gave the

desired product as a light yellow liquid, which was dried under vacuum (0.15 mm Hg) at

70-100 °C overnight.

[Cg-mimlCHaCGz (159) was prepared in 89% yield as a liquid. 'H NMR

(CDCI3): 6 0.87 (t, J=6.8 Hz, 3H), 1.31 (m, lOH), 1.88 (m, 2H), 2.01 (s, 3H), 4.08 (s, 3H),

4.29 (t, J=7.3 Hz, 2H), 7.17 (t, J=1.7 Hz, IH), 7.22 (t, J=1.7 Hz, IH), 11.66 (s, IH).

[Cg-mimlNOa (162) was prepared in 90% yield as a liquid. 'H NMR (CDCI3): 8

0.85 (t, J=6.7 Hz, 3H), 1.29 (m, lOH), 1.87 (m, 2H), 4.05 (s, 3H), 4.25 (t, J=7.4 Hz, 2H),

7.49 (t, J=1.8 Hz, IH), 7.58 (t, J=1.8 Hz, IH), 9.89 (s, IH). IR: 3155, 3121, 2921, 2859,

1573,1467,1170,830,770 cm'.

[Cg-mimlCFaCGz (163) was obtained in 85% yield as a liquid. 'H NMR (CDCI3):

8 0.87 (t, J=6.7 Hz, 3H), 1.27 (m, lOH), 1.87 (m, 2H), 4.03 (s, 3H), 4.24 (t, J=7.4 Hz,

2H), 7.34 (t, J=l .8 Hz, IH), 7.43 (t, J=l .8 Hz, IH), 10.25 (s, IH). "F NMR (CDCI3): 8 -

75.60. IR: 3420, 3149, 3094, 2957, 2929, 2858, 1688, 1575, 1469, 1202, 1171, 1127,

827, 801,719. Anal. Calcd. for C,4H23F3N202: C 54.53, H 7.52, N 9.09, found C 54.37, H

7.80, N 9.15.

127 4.4.5. Preparation of l-Benzhydrvl-3-alkylimidazolium Bis(trifluoromethylsulfonyl)imide Ionic Liquids

Ionic liquids 165-168 were prepared from the corresponding chlorides by a metathesis reaction with LiN(S02CF3)2 in water according to a procedure developed in this research.'^"

[(C5H5)2CH-mim]N(S02CF3)2 (165) was obtained in 91% yield as a viscous liquid. 'H NMR (CDCI3): 8 3.90 (s, 3H), 6.85 (s, IH), 7.10 (t, J=1.8 Hz, IH), 7.22 (m,

4H), 7.36 (t, J=l .8 Hz, IH), 7.42 (m, 6H), 8.47 (s, IH). IR 3152, 3036,2964, 1574, 1555,

1455, 1348, 1182, 1053 cm'. Anal. Calcd. for C,9H,7F6N304S2: C 43.10, H 3.24, N 7.94; found C 43.36, H 3.37, N 7.89.

[(CsHs)2CH-C2im]N(S02CF3)2 (166) was obtained in 89% yield as a viscous liquid. 'H NMR (CDCI3): 8 1.52 (t, J=74 Hz, 3H), 4.25 (t, J=7.3 Hz, 2H), 6.90 (s, IH),

7.12 (t, J=1.8 Hz, IH), 7.20 (m, 4H), 7.39 (m, 7H), 8.60 (s, IH). IR 3147, 3036, 2989,

1576, 1551, 1455, 1351, 1193, 1056 cm'. Anal. Calcd. for C2oH,9F6N304S2: C 44.20, H

3.52, N 7.73; found C 44.53, H 3.51, N 7.69.

[(CsH5)2CH-C3im]N(S02CF3)2 (167) was obtained in 90% yield as a viscous liquid. 'H NMR (CDCI3): 6 0.93 (t, J=74 Hz, 3H), 1.90 (sixt, J=7.4 Hz, 2H), 4.15 (t,

J=7.3 Hz, 2H), 6.92 (s, IH), 7.12 (t, J=l .8 Hz, IH), 7.19 (m, 4H), 7.40 (m, 7H), 8.59 (s,

IH). IR 3145, 3036, 2972, 2883, 1588, 1550, 1455, 1351, 1193, 1056 cm'. Anal. Calcd. for C2,H2,F6N304S2: C 45.24, H 3.80, N 7.18; found C 45.45, H 3.86, N 7.47.

[(C6H5)2CH-C4im]N(S02CF3)2 (168) was in obtained 91% yield as a viscous liquid. 'H NMR (CDCI3): 8 0.94 (t, J=74 Hz, 3H), 1.36 (m, 2H), 1.90 (pent, J=6.3 Hz,

2H), 4.20 (t, J=7.5 Hz, 2H), 6.99 (s, IH), 7.10 (t, J=1.8 Hz, IH), 7.19 (m, 4H), 7.36 (t,

J=1.8 Hz, IH), 7.42 (m, 6H), 8.81 (s, IH). IR 3145, 3036,2972,2883,1588,1550,1455,

128 1351, 1193, 1056 cm'. Anal. Calcd. for C22H23F,N304S2: C 46.23, H 4.06, N 7.35; found C 46.34, H 4.05, N 7.31.

4.5. References

1. R. S. Macomber, A Complete Introduction to Modern NMR Spectroscopy. New York: John Wiley, 1998.

2. A. A. Fannin, Jr. L. A. King, J. A. Levisky, J. S. Wilkes, 7. Phys. Chem. 1984, 88, 2609.

3. J. S. Wilkes, J. A. Levisky, J. L. Pflug, C L. Hussey, T. B. Scheffer, Anal. Chem. 1982,54,2378.

4. P. Bonhote, A.-P. Dias, N. Papageorgiou, K. Kalyanasundaram, M. Gratzel, Inorg. Chem. 1996,35, lies.

5. J. Dupont, P. A. Z. Suarez, R. F. de Souza, R. A. Burrow, J.-P. Kintzinger, Chem. Eur. J. 2000,6,2311.

6. A. G. Avent, P. A. Chaloner, M. P. Day, K. R. Seddon, T. Welton, 7. Chem. Soc, Dalton Trans. 1994,3405.

7. J. D. Holbrey, K. R. Seddon, 7. Chem. Soc, Dalton Trans. 1999,2133.

8. A. D. Headley, N. M. Jackson, 7. Phys. Org. Chem. 2002, 75,52.

9. (a) M. V. Baker, B. W. Skelton, A. H. White, C. C. Williams, 7. Chem. Soc, Dalton Trans. 2001, 111; (b) C. J. Mathews, P. J. Smith, T. Welton, A. J. P. White, D. J. Williams, Organometallics, 2001,20, 3848.

10. A. Elaiwi, P. B. Hitchcock, K. R. Seddon, N. Srinivasan, Y.-M. Tan, T. Welton, J. A. Zora, 7. Chem. Soc, Dalton Trans. 1995,3467.

11. (a) M. Maroncelli, V. P. Kumar, A. Papazyan, 7. Phys. Chem. 1993,97. 13; (b) M. Cho, M. Du, N. F. Scherer, G. R. Fleming, S. Mukamel, 7. Chem. Phys. 1993, 99, 2410.

129 12.(a) S. Chun, S. V. Dzyuba, R. A. Bartsch, Anal. Chem. 2001, 73, 3737; (b) S. V. Dzyuba, R. A. Bartsch, ChemPhysChem. 2002,5,161.

13.(a) E. L. Quitevis, M. Neelakandan, 7. Phys. Chem. 1996,100, 10005; (b) M. Neelakandan, D. Pant, E. L. Quitevis, Chem. Phys. Lett. 1996,265, 283; (c) M. Neelakandan, D. Pant, E. L. Quitevis, 7. Phys. Chem. A 1997,101,2936.

130 CHAPTER V

APPLICATIONS OF ROOM-TEMEPRATURE

IONIC LIQUIDS: EN ROUTE TO

DESIGNER SOLVENTS

As pointed out earlier, the possibility for almost limitless structural modifications in ionic liquids is advantageous over the limited structural possibilities in conventional molecular organic solvents. Moreover, an array of structural properties, including phase transitions, density, viscosity, and polarity, can be tailored by simple structural modifications of the ionic liquid. This is particularly important since the nature of the ionic environment does not change. In this view, one can anticipate the fine-tuning of properties of a certain ionic liquid for a particular chemical process. Collectively this leads to the idea of the ionic liquids being "designer-solvents."' Coined by Professor

Seddon a few years ago, this term became a fascinating, yet challenging, aspect of research on ionic liquids. In this research, several attempts to address the issue of the

"designer-solvent" ability have been undertaken.

5.1. Application of Room-Temperature Ionic Liquids in Competitive Alkali Metal Salts Extraction by a Crown Ether

Room-temperature ionic liquids have emerged as a versatile alternative to molecular organic solvents for a wide variety of organic reactions.^ However, applications of these novel solvents in separation processes have received much less attention. Several 1,3-alkyIsubstituted imidazolium hexafluorophosphate and bis(trifluoromethylsulfonyl)imide room-temperature ionic liquids were found to be superior to an array of molecular solvents for stiontium extraction ion from aqueous

131 solutions by dicyclohexano-18-crown-6.' Subsequentiy, extractions of other metal ions from aqueous solution into selective I-alkyl-3-methylimidazolium hexafluorophosphates by several crown ethers were reported." Also, the development of so-called "task- specific" ionic liquids containing heavy-metal ions chelating units allowed combination of the extiactant and solvent in one unit.'

In collaboration with Sangki Chun, another member of the Bartsch Research

Group, the influence of structural variations on the efficiency and selectivity of competitive alkali metal cation extraction from aqueous solutions by dicyclohexano-18- crown-6 (DC18C6) into [C„-mim]PF6, with n = 4-9, ionic liquids 84-89 was investigated.*

A set of conventional molecular solvents (chloroform, nitrobenzene and 1-octanol) was used for comparison. Transfer of alkali metal salts from their aqueous solutions into these molecular solvents was undetectable even with the presence of the crown ether.

This effect is in agreement with literature observations.'

In the absence of the crown ether some transfer of alkali metal chlorides into the ionic liquids was noted. The efficiency of the extraction selectivity was fairly low, less than 7 %. However, the tiend of extraction selectivity was consistent with the relative hydrophobicities of the alkali metal cations, Cs"^ > Rb* > K"^ > Li"^ = Na*. Also, the efficiency of the transfer decreased when more hydrophobic room-temperature ionic liquids were utilized.

In the presence of DC18C6, a marked change in the exti-action selectivity was noted. Results for competitive solvent extraction of aqueous solutions of the alkali metal chlorides with DC18C6 in [C„-mim]PF6 ionic liquids are shown in Figure 5.1. In

132 Loading, %

Figure 5.1. Influence of the length of the alkyl group (n) on the efficiency of competitive alkali metal cation extraction from aqueous solutions by DC18C6 in [C„-mim]PF6 ionic liquids correlation with the relative complexing abilities of 18-crown-6 ligands for the alkali metal cations,' the observed selectivity was K^ > Rb* > Cs* > Na* a Li^. Again, the efficiency of the metal ion extraction diminished with elongation of the alkyl group on the imidazolium cation. The unusual behavior of [Ce-mimlPF^ ionic liquid remains anomalous at present.

Cation/cation selectivities are important parameters in designing an efficient system for the competitive metal ion extraction systems.^ In general, this can be achieved by an appropriate choice of ligand. The use of ionic liquids opens a possibility for designing a solvent system, which would govern the extraction selectivity. The influence of structural variation within the imidazolium cation on the K'^/Cs'^ and K'^/Rb'^ selectivities in competitive alkali metal extraction by DC18C6 is shown in Figure 5.2.

The K^'/Cs'^ selectivity increase significantiy as the 1-alkyl group of the imidazolium cation is elongated. Thus, these results show that a decrease in extiaction efficiency is coupled with an increase in extraction selectivity.

133 8-|

6- K+/Rb+ Selectivity 4 - ratio K+/CS+

2-1

0 1^ 1^ 1^ 1^ 4 5 6 7 8 9

Figure 5.2. Influence of the length of the alkyl group in the imidazolium cation on the KVCs"^ and K'^/Rb'" selectivities in competitive alkali metal extraction from aqueous solution from DC18C6 in [C4-mim]PF6 ionic liquids.

The competitive solvent extraction of alkali metal salts from their aqueous solutions into common molecular organic solvents by crown ethers depends on the identity of alkali metal salt anions.* In the case of [C„-mim]PF6 ionic liquids 84-89, the alkali metal cation extraction was unaffected by varying the aqueous-phase anion from chloride to nitrate to sulfate.

5.2. Ionic Liquids as Solvents for Enzymatic Reactions: Enzyme-Catalyzed. Lactam-Ring Opening Reactions in Ionic Liquids

Since it was demonstrated that enzymes can effectively function in organic solvents,' enzymatic processes in organic media became a powerful addition to the arsenal of synthetic organic chemistry. Numerous enzyme assisted organic reactions can be performed in organic solvents, affording high regio- and enantioselectivities.'"

However, there is still a challenge of determining the optimal solvent, which enhances

134 both enzymatic activity and selectivity." Recently, several pioneering reports appeared, which demonstrate that room-temperature ionic liquids can be utilized successfully in a number of bioprocesses.

The first effective enzyme-catalyzed functional group transformation was accomplished for hydration of 1,3-dicyanobenzene in a two-phase system ([C4-mim]PFe - water)." The ionic liquid was shown to be a "greener" alternative to hazardous toluene, being less destructive towards the R312 cells. Recovery of both the solvent and the biocatalyst could be easily achieved because of reduced aggregation of the cells.

A subsequent study utilized water-miscible [C4-mim]BF4 and water-immiscible [C4-mim]PF6 ionic liquids in a number of lipase - catalyzed reactions (Scheme 5.1)." An

,0R R'OH Q lipase, Ionic liquid

NHa lipase, ionic liquid

H2O2 / RCO2H lipase, ionic liquid

Scheme 5.1. Reported examples of lipase - assisted organic transformations in ionic liquids. interesting feature of the transesterification of reaction was that the reaction of secondary alcohols proceeded more efficient in [C4-mim]PF6 ionic liquid, whereas in case of a primary alcohol, a better conversion was observed in tert-h\xiy\ alcohol. Amminolysis in

[C4-mim]BF4 ionic liquid was faster, but less efficient process as compared to conventionally used tert-h\xiy\ alcohol. Epoxidation of cyclohexane was not as effective

135 in the ionic liquids as in conventionally used acetonitrile. Overall, the advantage of using ionic liquids was simplified isolation of the products and recycling of the ionic liquid - enzyme system.

A fine balance between the nature of ionic liquids and various lipases was demonstiated in enzymatic kinetic resolution of secondary alcohols (Scheme 5.2).'" It

^,, vinyl acetate ^,, OH lipase OH OAc Ar R ionicliquid Ar R Ar R

Ar = [TT I[jr ^ R = Me, CICH2 O O^CHg rj'^^^CHs

Scheme 5.2. Enzymatic kinetic resolution of secondary alcohols in ionic liquids.

was demonstrated that it is possible to find specific ionic liquid - lipase combinations that afford very efficient, highly enantioselective resolution.'"* Several ionic liquids appeared to be superior to conventional solvents, such as tetrahydrofuran and toluene.'"*"

The latest breakthrough demonstrated a high enantio- and regioselectivity in a sugar acylation reaction performed in ionic liquids (Scheme 5.3)" that is superior to conventional solvents." Monoacylation of the primary alcohol group is favored in ionic liquids; whereas, diacylation is common is common in molecular solvents. The advantage of using ionic liquids comes from greater solubility of glucose and its derivatives in these solvents, than in such molecular solvents as ferf-butyl alcohol, acetone and THF.

136 OH OH OH 1,0H -r^^^e i^^^ i^^^

HO^^^AQH solvent ^'^'^^'v^OH ' ^"°^^^^^^^OAc OH OH 6H

Major in ionic liquids Major in molecular solvents Scheme 5.3. Glucose acylation in ionic liquids and molecular organic solvents.

Collectively, these results demonstrate that ionic liquids hold considerable potential as media for organic enzyme-assisted transformations. Broadening the scope of applications of ionic liquids in bioorganic and biochemical research will be of great interest and importance. Unfortunately, no examples are known.

Understanding the mechanisms of enzymatic processes is an important area of biological and chemical research.'* By lowering the temperature of the specific reaction, possible intermediates might be observed or trapped to provide evidence for a particular pathway. Cryogenic solvents are required to achieve this goal. A commonly used cryogenic solvent system is an aqueous solution of glycerol containing 0.1 mM ammonium sulfate, (NH4)2S04. This system allows enzymes to be stored, and measurements on their activity to be performed at -20 °C. Further lowering of the temperature would be beneficial for trapping the intermediates of the enzymatic hydrolysis. Unfortunately, that requires additional amounts of (NH4)2S04, which leads to an appreciable decrease of activity of the enzyme. Ionic liquids, which possess low phase tiansition temperatures, are potentially useful for these purposes.

A collaborative project on testing ionic liquids as cryogenic solvents or co- solvents was initiated with the Shaw Research Group. For a model reaction, the p-lactam

137 ring opening reaction of niti-ocefin (Figure 5.3) by Bacillus cereus 5/B/6 metallo |3- lactamase was selected.'^

CO2H ^ ^ ,^ ^ O2N ^^ ^NOs

Figure 5.3. Structure of nitrocefine.

Ethylammonium nitrate, bis(ethylammonium) sulfate and l-butyl-3-methyl- imidazolium bromide (1) along with other imidazolium-containing ionic liquids, such as

[C4-mim]N03 and [C4-mim]NTf2, were tested as co-solvents for the P-Iactame ring opening reaction. Results for the enzyme activity in the lactame ring-opening reaction are shown in Figure 5.4. Results for EtNH3N03 and (EtNH3)2S04 ionic liquids were poor, since the enzyme activity diminished dramatically with an increase of concentration of ammonium salts. In case of [C4-mim]N03 some precipitation was noted. Therefore, the use of these ionic liquids was abandoned. One possible explanation for the observed phenomenon is that silver nitrate used for the preparation of this ionic liquid and the precipitate might be attributed to residual amounts of silver salts present in the liquid.

The [C4-mim]NTf2 ionic liquid being water immiscible, afforded a two-phase system, which turned out to be ineffective as well. Only the ionic liquid bromide 1 gave promising results. The enzyme retained its activity even at fairly high concentration of

[C4-mim]Br (1) ionic liquid.

138 100

75 4 EtNH3N03 Enzyme ^^ (EtNH3)2S04 activity, % "^ [C4-mim]Br 25-

0 0 12 3 Molarity of the ionic liquid

Figure 5.4. Enzyme activity in ionic liquid - water systems.

Importantly, the ionic liquid - water system remained in a liquid-like state even at

-20 °C. Based on these data, it is evident that imidazolium ionic liquids hold a considerable promise for this type of the reaction. Subsequent experiments will be focused on determining the enzyme activity at sub-ambient temperatures, such as -20 °C and -80 °C, and increasing our understanding of imidazolium-based ionic liquid structure on the enzyme activity.

5.3. Diels-Alder Reactions in Ionic Liquids

The Diels-Alder reaction is among the most useful reactions for carbon-carbon bond formation. Room-temperature ionic liquids have been shown to be suitable media for this reaction. One of the first examples of Diels-Alder reaction in ionic liquids utilized ethylammonium nitrate as a solvent for the cycloaddition reaction of cyclopentadiene and methyl acrylate (Scheme 54).'* Endo selectivity of 6.7 was

139 s:v C02CH3 -I-

CO2CH3 CO2CH3

Scheme 5.4. Diels-Alder reaction of cyclopentadiene and methyl acrylate.

achieved, making this ionic media comparable to molecular organic solvents and lithium perchlorate-diethyl ether mixtures. Also this reaction was successfully performed in several 1- alkyl-3-methylimidazolium room-temperature ionic liquids, including [C4- mim]BF4 and [C2-mim]CF3S03, to give selectivities comparable to molecular organic solvents.'^ Subsequently, a variety of Diels-Alder reactions was performed in different ionic liquids.^"^ The endo selectivities of the reaction varied between 3-6. An asymmetric version of this reaction was performed in an ionic liquid containing a chiral anion.

However, the enantiomeric excess was negligible.

Lewis acidity of the reaction mixture is among the most important factors influencing the selectivity and reactivity of the Diels-Alder reaction. For this reason, haloaluminate room-temperature ionic liquids, which posses an adjustable Lewis acidity, served as excellent media providing high endo stereoselectivity and rate enhancement in a Diels-Alder reaction.^' However, the air- and water-sensitivity of haloaluminate room- temperature ionic liquids complicates their general use. On the other hand, addition of

Lewis acid catalysts, such as Sc(0Tf)3, to the [C^-mimlPF^ and [C„-mim]BF4 ionic liquids was also shown to facilitate the rate and enhance selectivity of a cycloaddition reaction .^^

Another experimental variable that has a significant influence on the endo-exo ratio of the products in the Diels-Alder reaction is the polarity of the solvent,^'with a

140 more polar solvent facilitating formation of the endo isomer. Applying the same reasoning, the cycloaddition reaction of cyclopentadiene and methyl acrylate (Scheme

5.4) in ethylammonium nitrate with polarity £^(30) = 61.6 kcal mol','" proceeds with 6.7 endo selectivity,'* whereas in [C4-mim]BF4 ionic liquid, whose ET(30) polarity is 52.5 kcal mol'," endo selectivity of 4.3 was achieved." This suggests the possibility that the selectivity of this cycloaddition reaction might be tailored by fine-tuning the polarity of room-temperature ionic liquids. Since, ethylammonium nitrate lacks the potential for structural modifications, imidazolium-based ionic liquids become very attractive systems to achieve this goal. This goal of polarity variation has been realized by the introduction of functional groups onto the imidazolium cation affording "functionalized" room- temperature ionic liquids 96,103,152,155 and 156 (Figure 3.2).

These room-temperature ionic liquids were employed as solvents for the Diels-

Alder reaction of cyclopentadiene and methyl acrylate (Scheme 5.4). This reaction is reported to be heterogeneous in ethylammonium nitrate and several others ionic liquids'*" with the endo-exo ratio depending on both the concentration of reactants and the reaction time. In this research, the reactions were homogeneous. The influence of concentration and reaction time was evaluated with [C3-mim]NTf2 (96) ionic liquid.

Over a range of concentrations of the reactants (0.3-1 M) and reaction times (2-24 hours), no change in the endo-exo product ratio was noted. With this information in hand, the

Diels-Alder reactions were performed using 0.3 M concentrations of freshly distilled cyclopentadiene and an equimolar amount of methyl acrylate in 2 ml of ionic liquid in a capped vial under magnetic stirring at room temperature over a 2-hour period. This was followed by extiaction of the products with hexanes, since these ionic liquids are miscible with diethyl ether. To assure that the ionic liquid was not tiansferred into the hexanes.

141 the volatiles were evaporated to afford a liquid, which was analyzed by 'H NMR spectioscopy. Once it was confirmed that the extract was free of ionic liquid, the mixture was subjected to characterization by GC. For [C,o-mim]NTf2 (103), the mixture of the reaction products was evaluated by 'H NMR spectroscopy only, due to some solubility of this ionic liquid in hexanes. Due to the small scale of the reaction, isolation of the products was not performed. The yields were estimated on the basis of residual peaks of dicyclopentadiene in the 'H NMR spectrum and GC. Methyl acrylate was not considered, since it could be removed in either evaporation step, or during the GC analysis, considering that its boiling point is very close to that of hexanes. In all cases, the yields for the Diels-Alder reaction were > 95%.

Results from reaction of cyclopentadiene with methyl acrylate in the room- temperature ionic liquids are presented in Table 5.1. A control experiment was performed with ethylammonium nitrate as solvent and the ratio of isomeric products from the cycloaddition reaction was shown to be in close agreement with literature data.'* A general correlation between the polarity of the ionic liquids and the stereoselectivity of the Diels-Alder is evident with greater polarity leading to higher endo/exo ratios.

142 Table 5.1. Endo/exo selectivity of the Diels-Alder reaction and its correlation with the

ionic liquid ET(30), kcal mol"' endo/exo^

[C3-mim]NTf2 52.0 4.3

[C,o-mim]NTf2 51.0 4.3"

[C6H5CH2-mim]NTf2 52.5 4.9

[CH30(CH2)2-mim]NTf2 54.1 5.7

[HO(CH2)2-mim]NTf2 61.4 6.1

[(C2H5)3NH]N03 61.6'" 6.4^

[C4-mim]BF4 52.5" 4.3"

* Determined by GC." Determined by 'H NMR spectroscopy.' A value of 6.7 is reported in reference 18.

This is the first example in which structural variation within a series of ionic liquids influences the course of an organic reaction. Moreover, with the simplicity of preparation for such functionalized ionic liquids, further "designer solvent" applications can be anticipated.

5.4. Conclusions

Results presented in this chapter reveal the versatility of ionic liquids. They have been employed as solvents or co-solvents in various applications, which range from analytical chemistry to biochemistry to organic chemistry. The room-temperature ionic liquids have been shown to be superior to conventionally used molecular solvents in competitive solvent extraction studies. The use of the imidazolium-containing ionic liquid 1 showed the potential of ionic liquids as cryogenic solvents for the study of mechanisms of biochemical processes. Structural variations within the imidazolium

143 cation have been shown to influence the selectivity of a Diels-Alder reaction. In each example, an influence of the structure of ionic liquid on a specific chemical process was demonstrated. Collectively, the data obtained in this research in combination with several literature reports, builds a strong foundation for the long lasting speculation of ionic liquids being "designer-solvents." It is expected that other examples will follow shortly.

5.5. Experimental Section

5.5.1. Materials

Ionic liquids were prepared according to literature procedures or as described in

Chapters 2 and 3. All of the ionic liquids gave spectroscopic and combustion analysis consistent with the proposed structures. Ethylammonium nitrate was provided by

Professor Robert Flowers, II (Texas Tech University). Chloroform, nitrobenzene and 1- octanol were washed with distilled water prior to use. Dicyclohexano-18-crown-6 (a mixture of cis-syn-cis and cis-anti-cis isomers) was purchased from Aldrich. Deionized water was prepared by passing distilled water through three Barnstead D8922 combination cartidges in series. Nitrocefine was purchased from Becton Dickenson and

Co. and used as received. Cyclopentadiene was obtained by distilling the dicyclopentadiene twice before use. GC analysis of the isomeric mixture of the Diels-

Alder reaction was performed on a HP-6850 gas chromatograph with a Carbowax 20M column.

144 5.5.2. Competitive Solvent Extraction of Alkali Metal Salts from Aqueous Solution in Ionic Liquids and Molecular Organic Solvent

Competitive solvent extraction experiments were performed as reported.'

5.5.3. Determination of Enzyme Activity in Ionic Liquids

Steady state kinetic assays were carried out using nitrocefin as a substrate according to a literature procedure.'*" Enzymatic activity assays were carried out at

30±0.1 °C in a neutral buffer solution (pH 7.0, 50 mM MOPS / 1 mM ZnS04) at various concentrations of each ionic liquid tested.

5.5.4. Representative Procedure for the Diels-Alder Reaction in Ionic Liquids

Freshly doubly distilled cyclopentadiene (0.20 g, 3.0 mmol) was added to 2 ml of room-temperature ionic liquid in a glass vial equipped with the magnetic stirrer. Methyl acrylate (0.27 ml, 3.0 mmol) was added and the vial was tightly capped. The reaction mixture was stirred for 2 h at room temperature, before being extracted with hexanes (3 x

7 ml). The hexanes were evaporated in vacuo and the residue was analyzed by 'H NMR spectroscopy and then by GC to obtain the isomer ratio.

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147