And Para-Substituted Allyl Phenyl Ethers Was Investigated

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Experimental and theoretical study of the regioselectivity of Claisen rearrangements of substituted allyl phenyl ethers

William Thomas Möller

Faculty of Physical Sciences University of Iceland 2020

Experimental and theoretical study of the regioselectivity of Claisen rearrangements of substituted allyl phenyl ethers

William Thomas Möller

60 ECTS thesis submitted in partial fulfillment of a Magister Scientiarum degree in Organic Chemistry

Advisor Benjamín Ragnar Sveinbjörnsson

MS Committee Benjamín Ragnar Sveinbjörnsson Krishna Kumar Damodaran

Master’s Examiner Haraldur Garðarsson

Faculty of Physical Sciences School of Engineering and Natural Sciences University of Iceland Reykjavik, May 2020

Experimental and theoretical study of the regioselectivity of Claisen rearrangements of substituted allyl phenyl ethers Claisen rearrangement of substituted allyl phenyl ethers (50 characters including spaces) 60 ECTS thesis submitted in partial fulfillment of a Magister Scientiarum degree in Chemistry

Faculty of Physical Sciences School of Engineering and Natural Sciences University of Iceland Hjarðarhagi, 2-6 107, Reykjavik Iceland

Telephone: 525 4000

Bibliographic information: William Thomas Möller, 2020, Experimental and theoretical study of the regioselectivity of Claisen rearrangements of substituted allyl phenyl ethers, Master’s thesis, Faculty of Physical Science, University of Iceland.

Printing: Háskólaprent, Fálkagata 2, 107 Reykjavík Reykjavik, Iceland, June 2020

Abstract

The regioselectivity of Claisen rearrangement with different meta-substituted and meta- and para-substituted allyl phenyl ethers was investigated. The main results were that in meta- substituent Claisen rearrangements the regioselectivity depends roughly on the electronic nature of the substituent. When the substituent is electron donating it favors the migration to unhindered side while when the substituent is electron withdrawing it favors migration towards the meta-substituent. In meta- and para-substituted aromatic Claisen rearrangement the results indicated that the para substituent does have influence on the A:B ratio. In most cases it seemed to amplify the preference of the meta-substituents. Two meta substituents were tried, methyl and chlorine with various other para-substituents. When methyl and chlorine were in meta position with hydrogen in para position they both preferred formation of isomer B. In most cases when hydrogen in para position was switched out for other substituents isomer B was still preferred.

Theoretical calculations were performed on allyl phenyl ethers with different meta substituents and meta- and para-substituents. The calculations were mostly in agreement with experimental data and in some cases, it could possibly explain different behavior than was expected. For example, an allyl phenyl ether with methyl as meta-substituents gave A:B ratio 1:1.20 but the methyl group was expected to be electron donating which should form more of isomer A. The calculations did predict that isomer A was lower in energy than isomer B, but that transition state of B was lower in energy than transition state of A suggesting the temperature for the reaction probably needed to be higher to get more of A.

Population analysis were performed with Mulliken, Löwdin, Hirshfeld and natural population analysis to analyze the influence of the substituents on the atomic charges on the reaction sides of the aryl and allyl group in the allyl phenyl ether. In fact, it was observed that the atomic charge on the carbon that forms the more dominant isomer is of higher negativity than the atomic charge on the carbon that forms the lesser isomer. When plotting the difference between the two carbon on the aryl ring versus B:A ratio a notable trend was observed. The atomic charges calculation methods were not always in agreement though. For example, NPA and MPA fail to agree with the other methods for Claisen rearrangement of allyl phenyl ether with fluorine as the meta substituent. This would have to be studied further with more methods!

Molecular orbital composition analysis was done on few allyl phenyl ethers. The analysis predicted there to be orbital coefficients on the allyl group for allyl phenyl ethers with fluorine, methyl and ethyl as substituents. When the calculations were expanded to more complex molecules, like allyl phenyl ethers with chlorine and bromine as meta-substituents the model failed to predict coefficients on the allyl group suggesting that, presumably, another level of theory could be better with better basis sets.

Útdráttur

Svæðisvendni fyrir Claisen umröðun á nokkrum meta setnum og meta og para setnum allýl phenýl eterum var rannsökuð. Helstu niðurstöður rannsóknarinnar fyrir meta setnu allýl phenýl eterana er að svæðisvendnin veltur gróflega á elektrónískum áhrifum frá meta hópnum. Þegar hópurinn er rafgefandi þá mjakast allýl hópurinn í átt að óhindraði stöðunni til að mynda byggingarhverfu A og þegar hópurinn er raftogandi þá vill allýl hópurinn fara í átt að meta hópnum til að mynda byggingarhverfu B. Í Claisen umröðun þegar það eru meta og para hópar var fundið út að para hópurinn hefur áhrif á A:B hlutfallið. Í mörgum tilfellum virðist vera að para hópurinn magnar áhrifin frá meta hópnum. Tveir meta hópar voru prufaðir, metýl og klór með mörgum mismunandi para hópum. Þegar metýl og klór hóparnir voru í meta stöðu með vetni í para stöðu þá myndaðist meira af byggingarhverfu B og í mörgum tilfellum þegar vetni í para stöðu er skipt út fyrir aðra hópa þá myndaðist samt meira af byggingarhverfu B.

Kennilegir reikningar voru framkvæmdir á völdum allýl fenýl eterum með mismunandi meta hópa og meta og para hópa. Reikningarnir pössuðu nokkuð vel við niðurstöður frá tilraununum og í sumum tilvikum geta reikningarnir hugsanlega útskýrt frávik. Eins og í tilfelli Claisen umröðunar þar sem metýl er meta hópur og A:B hlutfallið var 1:1.20 en búist var við að metýl hópurinn væri rafgefandi og meira af byggingarhverfu A átti að myndast. Reikningarnir sýndu að varmafræðilega ætti meira að myndast af byggingarhverfu A. Hins vegar sýndu reikningar að byggingarhverfa B væri hraðafræðilega ákjósanlegri og að hugsanlega gæti það verið að spila inní afhverju hlutfallið er B í vil. Hugsanlega gæti þurft að hafa hærri hita fyrir sumar Claisen umraðanirnar til að fá meira af varmafræðilega myndefninu.

Reikningar voru framkvæmdir með Mulliken, Löwdin, Hirshfeld og náttúrulegri fjölda greiningum (e. population analysis) til að sjá hvort mismunandi sethópar hefðu áhrif á atóm hleðslur innan sameindanna. Helst var þá skoðað hvernig atóm hleðslurnar breyttust á kolefnunum sem taka þátt í umröðuninni á arýl hringnum og allýl hópnum. Helstu niðurstöður frá þeim reikningum voru þær að mismunandi sethópar hafa áhrif á atóm hleðslurnar og er það kolefni sem tekur þátt í að mynda nýtt kolefnis-kolefnis tengi í Claisen umröðuninni sem myndar meira af einni byggingarhverfu með hærri neikvæða hleðslu heldur en kolefnið sem tekur þátt í að mynda kolefnis-kolefnis tengi af þeirri byggingarhverfu sem myndast minna af. Þær kenningar sem voru prufaðar sýndu þó ekki alltaf sömu niðurstöðu. Í tilfelli þar sem meta hópur er flúor voru MPA og NPA ekki í samræmi við aðrar niðurstöður sem gefur til kynna að þetta þarf að skoða betur.

Reikningar voru framkvæmdir til að finna út samsetningu sameinda svigrúmanna. Það er að segja hversu mikið af sameinda svigrúminu situr á hverju atómi. Reikningarnir sýndu fram á að sameinda svigrúmin sitja á kolefnunum á allýl hópnum þegar meta hóparnir eru metýl, etýl og flúor. Þegar reikningarnir voru framkvæmdir fyrir flóknari kerfi með stærri atóm eins og klór og bróm þá sýndu þeir ekki sömu niðurstöðu sem gæti þýtt að það þurfi að prufa reikningana með annarri kenningu fyrir reikninga innan skammtafræðinnar.

Dedication

I want to dedicate the work of this research to my parents. My mother who loved and raised me and my father who worked away from home for many days of the year so we would never need anything and for being my biggest role model in the world!

Table of Contents

List of Figures ...... viii

List of Tables ...... xii

Acknowledgements ...... xv

1 Introduction ...... 1

2 Results and Discussions ...... 5 2.1 Sample definition and ratio determination ...... 5 2.2 Meta-substituted Allyl Phenyl Ethers ...... 8 2.3 Meta- and para-substituted Allyl Phenyl Ethers ...... 12 2.4 Theoretical calculations ...... 15 2.4.1 Reaction energies ...... 15 2.4.2 Population analysis and atomic charges ...... 18 2.4.3 Molecular orbital analysis ...... 25

3 Conclusions ...... 29

4 Experimental section ...... 31 4.1 General information ...... 31 4.2 Synthetic protocols ...... 31 4.2.1 General synthesis of allyl aryl ethers ...... 31 4.2.2 General protocol for the Claisen rearrangement ...... 32 4.3 NMR analysis of products ...... 32 4.3.1 1-(allyloxy)-3-fluorobenzene (1a)...... 32 4.3.2 1-(allyloxy)-3-chlorobenzene (1b) ...... 33 4.3.3 1-(allyloxy)-3-bromobenzene (1c) ...... 34 4.3.4 1-(allyloxy)-3-iodobenzene (1d) ...... 35 4.3.5 1-(allyloxy)-3-methylbenzene (1e) ...... 36 4.3.6 1-(allyloxy)-3-ethylbenzene (1f) ...... 37 4.3.7 1-(allyloxy)-3-(tert-butyl)benzene (1g) ...... 38 4.3.8 1-(allyloxy)-3-1,1’biphenyl (1h) ...... 39 4.3.9 1-(allyloxy)-3-(trifluoromethyl)benzene (1i)...... 40 4.3.10 N-(3-(allyloxy)phenyl)acetamide (1j) ...... 41 4.3.11 1,3-bis(allyloxy)benzene (1k) ...... 42 4.3.12 4-(allyloxy)-1-fluoro-2-methylbenzene (2a) ...... 43 4.3.13 4-(allyloxy)-1-chloro-2-methylbenzene (2b) ...... 44 4.3.14 4-(allyloxy)-1,2-dimethylbenzene (2c) ...... 45 4.3.15 4(allyloxy)-1-isopropyl-2-methylbenzene (2d) ...... 46 4.3.16 (4-(allyloxy)-2-methylphenyl)(methyl)sulfane (2e) ...... 47 4.3.17 4-(allyloxy)-2-chloro-1-fluorobenzene (2f) ...... 48

v 4.3.18 4-(allyloxy)-1,2-dichlorobenzene (3a) ...... 49 4.3.19 4-(allyloxy)-2-chloro-1-methylbenzene (3b) ...... 50 4.3.20 4-(allyloxy)-2-chlorobenzonitrile (3d) ...... 51 4.3.21 Products from Claisen rearrangement of 1-(allyloxy)-3-fluorobenzene (1a) ...... 52 4.3.22 Products from Claisen rearrangement of 1-(allyloxy)-3-chlorobenzene (1b) ...... 53 4.3.23 Products from Claisen rearrangement of 1-(allyloxy)-3-bromobenzene (1c) ...... 54 4.3.24 Products from Claisen rearrangement of 1-(allyloxy)-3-iodobenzene (1d) ...... 55 4.3.25 Products from Claisen rearrangement of 1-(allyloxy)-3-methylbenzene (1e) ...... 56 4.3.26 Products from Claisen rearrangement of 1-(allyloxy)-3-ethylbenzene (1f) ...... 57 4.3.27 Products from Claisen rearrangement of 1-(allyloxy)-3-(tert- butyl)benzene (1g) ...... 58 4.3.28 Products from Claisen rearrangement of 3-(allyloxy)-1,1'-biphenyl (1h) ...... 59 4.3.29 Products from Claisen rearrangement of 1-(allyloxy)-3- (trifluoromethyl)benzene (1i) ...... 60 4.3.30 Products from Claisen rearrangement of N-(3- (allyloxy)phenyl)acetamide (1j) ...... 61 4.3.31 Products from Claisen rearrangement of 1,3-bis(allyloxy)benzene (1k) ..... 62 4.3.32 Products from Claisen rearrangement of 4-(allyloxy)-1- fluoro-2- methylbenzene (2a) ...... 63 4.3.33 Products from Claisen rearrangement of 4-(allyloxy)-1- chloro-2- methylbenzene (2b)...... 64 4.3.34 Products from Claisen rearrangement of 4-(allyloxy)-1,2- dimethylbenzene (2c) ...... 65 4.3.35 Products from Claisen rearrangement of 4-(allyloxy)-1-isopropyl-2- methylbenzene (2d)...... 66 4.3.36 Products from Claisen rearrangement of (4-(allyloxy)-2- methylphenyl)(methyl)sulfane (2e) ...... 67 4.3.37 Products from Claisen rearrangement of 4-(allyloxy)-2-chloro-1- fluorobenzene (3a) ...... 68 4.3.38 Products from Claisen rearrangement of 4-(allyloxy)-1,2- dichlorobenzene (3b) ...... 69 4.3.39 Products from Claisen rearrangement of 4-(allyloxy)-2-chloro-1- methylbenzene (3c) ...... 70 4.3.40 Products from Claisen rearrangement of 4-(allyloxy)-2- chlorobenzonitrile (3d) ...... 71

5 Computational calculations ...... 72 5.1 General information ...... 72 5.2 Orca input files ...... 73 5.2.1 Claisen rearrangement of 1-(allyloxy)-3-fluorobenzene (1a) ...... 73 5.2.2 Claisen rearrangement of 1-(allyloxy)-3-chlorobenzene (1b) ...... 78 5.2.3 Claisen rearrangement of 1-(allyloxy)-3-bromobenzene (1c) ...... 84

vi 5.2.4 Claisen rearrangement of 1-(allyloxy)-3-methylbenzene (1e) ...... 89 5.2.5 Claisen rearrangement of 1-(allyloxy)-3-ethylbenzene (1f) ...... 95 5.2.6 Claisen rearrangement of 1-(allyloxy)-3-(trifluoromethyl)benzene (1i) .... 100 5.2.7 Claisen rearrangement of 4-(allyloxy)-1-fluoro-2-methylbenzene (2a)..... 106 5.2.8 Claisen rearrangement of 4-(allyloxy)-1-chloro-2-methylbenzene (2b) .... 112 5.2.9 Claisen rearrangement of 4-(allyloxy)-1,2-dimethylbenzene (2c)...... 118 5.2.10 Claisen rearrangement of 4-(allyloxy)-2-chloro-1-fluorobenzene (3a) ..... 124 5.2.11 Claisen rearrangement of 4-(allyloxy)-1,2-dichlorobenzene (3b) ...... 129 5.2.12 Claisen rearrangement of 4-(allyloxy)-2-chloro-1-methylbenzene (3c) .... 135

References ...... 141

Appendix A ...... 145

vii List of Figures

Figure 1.1: Example of nucleophilic substitution which show substituent effects...... 1

Figure 1.2: Nitration of substituted benzene. The first one is chlorobenzene where para position is preferred. The second one is di substituted benzene where the nitro group prefers to be close to the methyl group...... 2

Figure 1.3: The aliphatic and aromatic Claisen rearrangement...... 3

Figure 1.4: A:B ratio when H as para-substituent is switched for two different groups. This experiment was performed by Gozzo and co-workers.11 ...... 4

Figure 2.1: Shows reaction scheme where intermedidates and isomer A and isomer B are defined...... 5

Figure 2.2: (a) 1H NMR analysis for reactant in 1a. (b) Claisen rearrangement product from 1a. (c) Claisen rearrangement product from 1b...... 6

Figure 2.3: (a) An example of the aromatic region of the NMR spectrum for the Claisen rearrangement product of a meta- and para-substituted allyl aryl ether, 2b. (b) The full 1H NMR spectrum for the Claisen rearrangement products of 2b showing how the product ratios of the aromatic region match with the product ratio measured by the alkyl region...... 7

Figure 2.4: Inductive and resonance effect of alkyl group when attached to atom or sp2 or sp-hybridized carbon. The picture is reproduced from same picture from article from Luis Salvatella.19 ...... 10

Figure 2.5: Shows a possible scheme of the reaction in 1k...... 11

Figure 2.6: Scheme where the transition state and intermedidates are defined for computer calculations...... 15

Figure 2.7: The reaction above shows addition of HBr to 1,3-butadiene under kinetic vs. thermodynamic control. The reaction below shows sulfonation of naphthalene under kinetic vs. thermodynamic control.32,34 ...... 17

Figure 2.8: (a) Optimized structure of reactant in 1b, (b) MEP of the optimized structure of reactant in 1b...... 19

Figure 2.9: Graph of atomic charges from MPA, LPA, HPA, NPA for the reactants from 1a-c, 1e-f, and 1i. The X-axis shows the atoms that atomic charges were calculated for. The Y-axis shows the calculated atomic charges...... 20

Figure 2.10: Graph of atomic charges from MPA, LPA, HPA, NPA for the reactants from 1e, and 2a-c. The X-axis shows the atoms that atomic charges were calculated for. The Y-axis shows the calculated atomic charges...... 22

viii Figure 2.11: Graph of atomic charges from MPA, LPA, HPA, NPA for the reactants from 1b, and 3a-c. X-axis the atoms that atomic charges were calculated for. Y-axis shows atomic charges...... 23

Figure 2.12: (a) Charge difference between carbon 1 and 3 from HPA a plot of charge difference vs B:A ratio. (a) Charge difference between carbon 1 and 3 from NPA a plot of charge difference vs B:A ratio...... 25

Figure 2.13: (a) Optimized structure of 1a, the atoms of interest are labelled. (b) Shows HOMO and LUMO of aliphatic and aromatic Claisen rearrangement, the picture is reproduced from same picture from article from Gozzo and co-workers.11 ...... 26

Figure 2.14: (a) HOMO of 1a, (b) Shows LUMO of 1a, (c) HOMO of 1e, (d) Shows LUMO of 1e ...... 27

Figure 4.1: 1H NMR of 1-(allyloxy)-3-fluorobenzene...... 32

Figure 4.2: 1H NMR of 1-(allyloxy)-3-chlorobenzene...... 33

Figure 4.3: 1H NMR of 1-(allyloxy)-3-bromobenzene...... 34

Figure 4.4: 1H NMR of 1-(allyloxy)-3-iodobenzene...... 35

Figure 4.5: 1H NMR of 1-(allyloxy)-3-methylbenzene...... 36

Figure 4.6: 1H NMR of 1-(allyloxy)-3-ethylbenzene...... 37

Figure 4.7: 1H NMR of 1-(allyloxy)-3-(tert-butyl)benzene...... 38

Figure 4.8: 1H NMR of 1-(allyloxy)-3-1,1’biphenyl...... 39

Figure 4.9: 1H NMR of 1-(allyloxy)-3-(trifluoromethyl)benzene...... 40

Figure 4.10: 1H NMR of N-(3-(allyloxy)phenyl)acetamide...... 41

Figure 4.11: 1H NMR of 1,3-bis(allyloxy)benzene...... 42

Figure 4.12: 1H NMR of 4-(allyloxy)-1-fluoro-2-methylbenzene...... 43

Figure 4.13: 1H NMR of 4-(allyloxy)-1-chloro-2-methylbenzene...... 44

Figure 4.14: 1H NMR of 4-(allyloxy)-1,2-dimethylbenzene...... 45

Figure 4.15: 1H NMR of 4-(allyloxy)-1-isopropyl-2-methylbenzene...... 46

Figure 4.16: 1H NMR of (4-(allyloxy)-2-methylphenyl)(methyl)sulfane...... 47

Figure 4.17: 1H NMR of 4-(allyloxy)-2-chloro-1-fluorobenzene...... 48

Figure 4.18: 1H NMR of 4-(allyloxy)-1,2-dichlorobenzene...... 49

ix Figure 4.19: 1H NMR of 4-(allyloxy)-2-chloro-1-methylbenzene...... 50

Figure 4.20: 1H NMR of 4-(allyloxy)-2-chlorobenzonitrile...... 51

Figure 4.21: 1H NMR of isomer A and B from Claisen rearrangement of 1-(allyloxy)- 3-fluorobenzene...... 52

Figure 4.22: 1H NMR of isomer A and B from Claisen rearrangement of 1-(allyloxy)- 3-chlorobenzene...... 53

Figure 4.23: 1H NMR of isomer A and B from Claisen rearrangement of 1-(allyloxy)- 3-bromobenzene...... 54

Figure 4.24: 1H NMR of isomer A and B from Claisen rearrangement of 1-(allyloxy)- 3-iodobenzene...... 55

Figure 4.25: 1H NMR of isomer A and B from Claisen rearrangement of 1-(allyloxy)- 3-methylbenzene...... 56

Figure 4.26: 1H NMR of isomer A and B from Claisen rearrangement of 1-(allyloxy)- 3-ethylbenzene...... 57

Figure 4.27: 1H NMR of isomer A and B from Claisen rearrangement of 1-(allyloxy)- 3-(tert-butyl)benzene...... 58

Figure 4.28: 1H NMR of isomer A and B from Claisen rearrangement of 3-(allyloxy)- 1,1’-biphenyl...... 59

Figure 4.29: 1H NMR of isomer A and B from Claisen rearrangement of 1-(allyloxy)- 3-(trifluoromethyl)benzene...... 60

Figure 4.30: 1H NMR of isomer A and B from Claisen rearrangement of N-(3- (allyloxy)phenyl)acetamide...... 61

Figure 4.31: 1H NMR of isomer A and B from Claisen rearrangement of 1,3- bis(allyloxy)benzene...... 62

Figure 4.32: 1H NMR of isomer A and B from Claisen rearrangement of 4-(allyloxy)- 1-fluoro-2-methylbenzene...... 63

Figure 4.33: 1H NMR of isomer A and B from Claisen rearrangement of 4-(allyloxy)- 1-chloro-2-methylbenzene...... 64

Figure 4.34: 1H NMR of isomer A and B from Claisen rearrangement of 4-(allyloxy)- 1,2-dimethylbenzene...... 65

Figure 4.35: 1H NMR of isomer A and B from Claisen rearrangement of 4-(allyloxy)- 1-isopropyl-2-methylbenzene...... 66

Figure 4.36: 1H NMR of isomer A and B from Claisen rearrangement of (4-(allyloxy)- 2-methylphenyl)(methyl)sulfane...... 67

x Figure 4.37: 1H NMR of isomer A and B from Claisen rearrangement of 4-(allyloxy)- 2-chloro-1-fluorobenzene...... 68

Figure 4.38: 1H NMR of isomer A and B from Claisen rearrangement of 4-(allyloxy)- 2-chloro-1-chlorobenzene...... 69

Figure 4.39: 1H NMR of isomer A and B from Claisen rearrangement of 4-(allyloxy)- 2-chloro-1-methylbenzene...... 70

Figure 4.40: 1H NMR of isomer A and B from Claisen rearrangement of 4-(allyloxy)- 2-chlorobenzonitrile...... 71

xi List of Tables

Table 2.1: Shows how samples are labelled. They first get a prefix and then a letter. The position of R1 and R2 can be seen in Figure 2.1...... 5

Table 2.2: The A:B ratio for the Claisen rearrangement of meta-substituted allyl phenyl ethers is given here...... 8

Table 2.3: A:B ratio results for meta- and para-substituted Claisen rearrangement...... 12

Table 2.4: Calculated Gibbs free energies for reactants and the relative energies to reactants of transition states for isomers A and B (TS A and TS B, respectively), and intermediates for isomer A and B (IA and IB, respectively) where the energy for reactant is in Hartrees and the relative energies are in kcal/mol. The table also shows energy differences between A and B transition states and intermedidates for each reaction...... 16

Table 2.5: Results from molecular orbital composition analysis with Hirshfeld. The values are given in percentages (%) and show the molecular orbital contribution on each atom. The labelled carbons are illustrated in Figure 2.13a...... 26

Table A 1: The atomic charges of selected atoms for reactant in the Claisen rearrangement 1a...... 145

Table A 2: The atomic charges of selected atoms for reactant in the Claisen rearrangement 1b...... 145

Table A 3: The atomic charges of selected atoms for reactant in the Claisen rearrangement 1c...... 145

Table A 4: The atomic charges of selected atoms for reactant in the Claisen rearrangement 1e...... 146

Table A 5: The atomic charges of selected atoms for reactant in the Claisen rearrangement 1f...... 146

Table A 6: The atomic charges of selected atoms for reactant in the Claisen rearrangement 1i...... 146

Table A 7: The atomic charges of selected atoms for reactant in the Claisen rearrangement 2a...... 146

Table A 8: The atomic charges of selected atoms for reactant in the Claisen rearrangement 2b...... 147

Table A 9: The atomic charges of selected atoms for reactant in the Claisen rearrangement 2c...... 147

xii Table A 10: The atomic charges of selected atoms for reactant in the Claisen rearrangement 3a...... 147

Table A 11: The atomic charges of selected atoms for reactant in the Claisen rearrangement 3b...... 148

Table A 12: The atomic charges of selected atoms for reactant in the Claisen rearrangement 3c...... 148

xiii

Acknowledgements

I want to express my sincere gratitude to my advisor Benjamín Ragnar Sveinbjörnsson for his guidance, patience, knowledge, and for providing me with the opportunity to work on this project and gaining more experience in the laboratory. I also want to express my gratitude to Vilhjálmur Ásgeirsson for helping me with theoretical calculations and just almost being a co-advisor!

I want to thank Dr. Sigríður Jónsdóttir for performing all NMR measurements and Dr. Svana Hafdís Stefánsdóttir for all the assistance she provided me. A special thanks to Professor Snorri Þór Sigurðsson and to doctoral candidate Anna-Lena Johanna Siegler for allowing me to use the third-year lab.

A special thanks go to all the teachers within the chemistry department for their endless support and understanding of my disability and giving me confidence to keep going and keep learning!

Finally, I want to thank my wife, brother and sister, and all my friends. My parents specially for everything they have surrendered for me to be able to fulfill my dreams!

1 Introduction

When it comes to organic synthesis, it is of significant importance to understand the regioselectivity of the reactions to be used, in order to better utilize them in the process of synthesizing target compounds. Many regioselective reactions are well understood and can be explained or rationalized using the stability of intermediates (e.g. Markovnikov’s rule for electrophilic addition reactions)1 or the stability of the products (Zaitsev‘s rule for elimination reactions).2

Simple experiments are often the most direct path towards establishing trends of regioselectivity within a specific type of reaction. The reaction is run for several compounds and the product distribution observed and recorded. Once enough reactions have been run, the results are compiled and analyzed in order to see the presence or absence of a clear trend. This enables us then to put forth a clearer hypothesis about the regioselectivity of the reaction in question and test the hypothesis further.

Understanding the transition states and thermodynamics of a reaction can be of significant help towards understanding why the observed regioselectivity (or lack thereof) is the way it is. When important steps are endergonic, the Hammond postulates informs us that the transition state bears a closer resemblance to the intermediate/product than the starting material or previous intermediate.3 If there is a significant difference in the stability of the intermediate/product, this often leads to a more significant regioselectivity. If the important steps are exergonic, that often leads to less regioselectivity since the transition states then bear a closer resemblance towards the starting material than the product. Improvements in computer power have allowed us to better estimate the thermodynamics of a reaction and more importantly, the energies of the various transition states in order to better understand why we observe the regioselectivity that we do. With faster computers we are also able to visualize better the molecular orbitals in order to see if they give us any further insight into the observed experimental results.

Substituents can also often influence a reaction pathway. One clear example of that is in the nucleophilic substitution reaction of the aromatic reagent shown below (Figure 1.1), where electron-donating groups push the reaction towards an SN1 mechanism by stabilizing the intermediate cation while electron-withdrawing groups would destabilize such a cation and 4 the reaction proceeds instead via the SN2 mechanism.

Figure 1.1: Example of nucleophilic substitution which show substituent effects.5

Another example of this type of reaction is electrophilic aromatic substitution. Regioselectivity in electrophilic aromatic substitutions is affected when a substituent is attached to the benzene ring. Some groups can be ortho-para directing while other groups can be meta directing.6 Substituents can generally be divided into two classes: activating or

1 deactivating. The activating groups add electron density to the ring while deactivating groups withdraw the electron density from the ring by inductive or resonance effects, respectively. In electrophilic aromatic substitutions, steric hindrance can also have effect on the directing ability of the substituent. When the benzene has two substituents, each exerts influence on subsequent substitution reactions. When there are two substituents the behaviour of their directing abilities can be categorised as either non-cooperative or cooperative. So what matters is if the group is activating or deactivating, and how the two substituents are aligned to each other. It matters if they are ortho to each other or meta or para to each other. Below in Figure 1.2 are two example that illustrate the regioselectivity in electrophilic aromatic substitutions. In the first example chlorobenzene reacts with nitric acid to make nitrobenzenes where the nitro group goes more to para position than ortho. In the second example the nitro group favours slightly being ortho to the methyl group instead of the chlorine group.7

The Claisen rearrangement is a carbon-carbon bond-forming chemical reaction discovered by Rainer Ludwig Claisen in 1912.8 The reaction proceeds by heating an allyl vinyl ether at 150-200°C without any reagents to produce a γ, δ-unsaturated aldehyde. The [3,3]- sigmatropic rearrangement of aryl allyl ethers is called aromatic Claisen rearrangement. It was Claisen that first described the thermal [3,3]-sigmatropic rearrangement of allyl vinyl ethers and allyl aryl ethers before then proposing the mechanism of this rearrangement.9 The mechanism behind aliphatic and aromatic Claisen rearrangement can be seen in Figure 1.3. Normally the aromatic Claisen rearrangement requires very high temperature, 180-225°C, which can lead to formation of several by-products through undesired side reactions. There are two major side reactions in the aromatic Claisen rearrangement: the first one is the rearrangement of the allylic moiety at the para position10 and the other one is the abnormal Claisen rearrangement.11 The first one can be avoided by having a para-substituent.

Figure 1.3: The aliphatic and aromatic Claisen rearrangement.

The most common preparation to prepare the allyl aryl ether is the Williamson ether synthesis. Allyl aryl ethers can be obtained by refluxing a phenol derivative with an allylic halide under basic conditions in acetone.4 This is convenient for the preparation of simple 10 aryl allyl ethers but there can be some side reactions like C-allylation (SN2 type reaction).

The reaction of study in this project is the Claisen rearrangement of meta- and para- substituted allyl aryl ethers. For non-substituted allyl-aryl ethers, the regioselectivity is not a significant issue as the allyl group migrates mostly to the neighboring ortho position, and due to the symmetry of the starting material, both products are equivalent. A similar observation can be found for the symmetric starting materials of para-substituted allyl aryl ethers. If one of the ortho-positions is occupied, the allyl group is expected to migrate to the other ortho position and although this reaction can also result in the allyl group migrating to a vacant para-position, that will not be studied in this thesis. It is however the meta-position that is of particular interest here.

The regioselectivity of the Claisen rearrangement of meta-substituted allyl aryl ethers reaction has been studied to some extent, but recent results have opened the door to more questions, which need to be answered. In 2002, Gozzo et al. published a paper with some interesting results.12 The regioselectivity of allyl aryl ethers with different substituents was explored along with theoretical calculations of the transition state energies, which helped to explain the observed regioselectivity. A simple molecular orbital analysis was not able to predict adequately the regioselectivity, but with improved computing power this could be achieved. Of significant interest was the comparison of 2 pairs of allyl aryl ethers (see Figure 1.4). Surprisingly, the presence or absence of a para-substituent had significant effect on the regioselectivity of this reaction. It can therefore be inferred that the para- and meta substituents can affect the regioselectivity of a Claisen rearrangement.

Figure 1.4: A:B ratio when H as para-substituent is switched for two different groups. This experiment was performed by Gozzo and co-workers.12

In this project, the Claisen rearrangement of a number of meta-substituted allyl aryl ethers will be executed along with the same reaction for some meta- and para-substituted allyl aryl ethers. The product distribution will be analyzed using NMR in order to see if substituent trends can be inferred from the results.

Furthermore, computational methods will be used to explore the transition state energies for selected reactions. Population analysis like Hirshfeld and natural population analysis will be performed to see if there is any electrostatic driving force behind the regioselectivity of the reaction.13 The molecular orbitals for selected reactants will be visualized and an attempt to rationalize the regioselectivity with frontier molecular orbital composition analysis will be made.14

4 2 Results and Discussions

2.1 Sample definition and ratio determination

There were 11 successful aromatic Claisen rearrangements with different meta-substituent and 9 successful aromatic Claisen rearrangements with different meta- and para- substituents. This is illustrated in Table 2.1.

Figure 2.1: Shows reaction scheme where intermedidates and isomer A and isomer B are defined.

The samples are defined first with number where 1 is the rearrangement with only meta- substituents and no para-substituents, the prefix 2 is the rearrangement where methyl group is fixed and the meta-substituent and para-substituents are varied, and the prefix 3 is the rearrangement where chlorine atom is fixed and the meta-substituent and different para- substituents are used. The letters stand for different substituents within each group. For example, in 1 the letter a stands for fluorine as the meta-substituent while b stands for chlorine as the meta-substituent. In 2 and 3, the letters stand for different para- substituents. The intermediates are also defined here as IA for isomer A and IB for isomer B. The intermediates will be used later in theoretical calculations.

Table 2.1: Shows how samples are labelled. They first get a prefix and then a letter. The position of R1 and R2 can be seen in Figure 2.1. Sample R1 Sample R1 R2 1a F 2a CH3 F 1b Cl 2b CH3 Cl 1c Br 2c CH3 CH3 1d I 2d CH3 iPr 1e CH3 2e CH3 SCH3 1f Et 3a Cl F 1g t-Bu 3b Cl Cl 1h Ph 3c Cl CH3 1i CF3 3d Cl CN 1j NHCOCH3 1k OCH2CH=CH2

5 The ratios between constitutional isomers A and B were determined by analyzing the crude 1H NMR spectra, so remaining starting materials and/or side products were sometimes observed. The two alkyl protons (e.g. H1 and H2 in the reactant in Figure 2.1) are the most important protons when it comes to later identifying the ratios of isomers A and B. An example of 1H NMR for 1a can been seen in Figure 2.2a, which shows that the peak around 4.5 ppm represents protons H1 and H2. After the Claisen rearrangement, this peak was split into two peaks, one represents isomer A and other represents isomer B. This is illustrated in Figure 2.2b and Figure 2.2c where the reactions of 1a and 1b are compared. The peak furthest to the left in b and c is the peak for the H1 and H2 protons of the reactants. As the reaction progresses the H1 and H2 peak of the reactant will start to shrink while the new product peaks start to grow. As one can see in Figure 2.2a there is also a multiplet for the H6 proton and doublet of doublets for H7 and H8 protons. These areas become very crowded after the Claisen rearrangement and are not considered when analysing the ratios between isomers A and B. The same can be said about the protons in the aromatic regions, at least for most of the meta-only substituted reactants.

Figure 2.2: (a) 1H NMR analysis for reactant in 1a. (b) Claisen rearrangement product from 1a. (c) Claisen rearrangement product from 1b.

It is however a little bit easier to analyse the aromatic region when the allyl phenyl ether is both meta- and para-substituted because the area is less crowded. In that way, one proton

6 will be eliminated from the aromatic region so there are only two aromatic protons that can be analysed in the respective products. On the reactant there are three aromatic protons, H3, H4, and H5 (see Figure 2.3). The allyl group can migrate to only one side, either it migrates to where H3 is or where H4 is. That means that for product A, only protons H3 and H5 should be found in the aromatic region. Furthermore, for protons H3 and H5 only two singlets should be observed, or doublets with a very low coupling constant. In the case of product B, only protons H4 and H5 should be found in the aromatic region. For protons H4 and H5, two doublets should be observed. An example of this, for sample 2b, is illustrated in Figure 2.3a where the protons in the aromatic region are analysed. The doublets represent the protons in isomer B while the singlets represent the protons in isomer A. The ratios are determined by integrating the peaks. In Figure 2.3b the two peaks of isomer A and isomer B for the alkyl protons are showed to be close to having double the integration compared to the protons in the aromatic region from the same product.

7 With isomer A and isomer B successfully identified, in most cases of meta- and para- substituted products, by the aromatic region, it can be seen that for the new alkyl peaks that form in the Claisen rearrangement, isomer A has the peak to the right while isomer B has the peak to the left. This trend has also been reported in the literature for several meta-substituted products of the Claisen rearrangement.15–17

2.2 Meta-substituted Allyl Phenyl Ethers

The results for the Claisen rearrangement of meta-substituted allyl phenyl ethers are summarized in Table 2.2. In this part of the project, the effect of different meta- substituents on the ratio between the A and B constitutional isomer products(from now on called isomer A and isomer B) was investigated and what could possibly cause the reaction to favor one isomer over the other.

Table 2.2: The A:B ratio for the Claisen rearrangement of meta-substituted allyl phenyl ethers is given here. Sample Meta substituent A:B product ratio 1a F 1:0.60 1b Cl 1:1.40 1c Br 1:1.50 1d I 1:1.50-1.65 1e CH3 1:1.20 1f Et 1:0.90 1g t-Bu 1:0.40 1h Ph 1:0.95 1i CF3 1:1.45 1j NHCOCH3 1:0.95 1k OCH2CH=CH2 1:0.35

From the results for the meta-substituted Claisen rearrangement reactions gathered in Table 2.2, it is observed that while there is regioselectivity, it is not so high. When investigating the topic, White and Slater found out that in all cases except for the electron-donating methoxy-substituent, rearrangement occurs primarily towards the substituted meta-position. Among the meta substituents they tried were methoxy-, methyl-, chlorine-, and cyano- substituents. The explanation provided by the authors was that the ratio between the isomers varied roughly between the electronic nature of the meta substituent. Thus electron donating substituents would favor migration to the unhindered position while electron withdrawing substituents would favor migration towards the substituted meta position.18 Here there rise two interesting cases to point out. In one case, 1a, the fluorine is expected to be electron withdrawing (see discussion later) but more of isomer A forms rather than isomer B. In the other case, 1e, the methyl group is expected to be electron donating (see discussion later) but more of isomer B forms rather than isomer A. The original conclusion by White and Slater does seem to hold up for the rest of the reactions tried out in this research but these two cases might imply that it is not as straight forward as just saying electron donating groups favor migration to the unhindered position while electron withdrawing group favor migration towards the substituted meta position.

8 For 1a, the one with fluorine as meta-substituent, isomer A is favored over isomer B. This differs from 1b, 1c, and 1d with the other halogens, where isomer B is favored over isomer A. Note also that the A:B ratio increases with the order 1a < 1b < 1c < 1d in favor of isomer B. When determining the A:B ratio in 1d a small pollution appeared around the peaks that were used to determine the A:B ratio in the NMR sample. This could have been because of some oxidation happening while the reaction was still in progress, and because of the oxidation some new unidentified by-products might have started to form.

To figure out the electrostatic nature of the substituent for the Claisen rearrangement, the electrophilic aromatic substitution was used as reference as the substituent is attached to a benzene ring in both cases. Since the reactions are mechanistically different, the substituents could behave differently for both reactions. In electrophilic aromatic substitution the halogens have shown the ability to be both electron withdrawing and donating. This is because of two opposing effects: electron donation by conjugation and electron withdrawal by induction. The halogens have lone pairs of electrons that they can donate to the ring. This electron-donating resonance is, however, not as good compared to if there were hydroxide or amine groups instead of halogens. When chlorine, bromine or iodine is the substituent, the problem is size. The 2p orbital of the carbon doesn’t overlap well with the 2p orbital for the halogen (3p for Cl, 4p for Br and 5p for I). Fluorine has 2p orbitals that are a better fit in size for overlap with the carbon 2p orbitals, but the problem is that fluorine is so electronegative that the 2p orbitals are much lower in energy than the 2p orbitals of carbon. So, conjugation in halobenzenes is expected to be weak and the inductive electron withdrawal ability is expected to take over and be the dominating factor in determining reactivity of halobenzenes in electrophilic aromatic substitutions.6

So, for electrophilic aromatic substitution of halobenzenes most electron density would first be removed from ortho position, then from meta position and finally the para position. Any conjugation of lone pairs would increase the electron density in the ortho and para positions. This makes the halogens ortho and para directing where both effects, conjugation and inductive, favor the para position. In a different reaction, the nitration of halobenzene, Taikei Ri and Henry Eyring found out that fluorine was better at directing the reaction towards the para position than ortho (85.0% para, 14.6% ortho). This could be compared to nitration of chlorobenzene (71.8% para, 28.2% ortho), bromobenzene (61.0% para, 39% ortho) and iodobenzene(56.9% para, 43.1% ortho).19

In the Claisen rearrangement of allyl m-X-phenyl ethers where the X is halogen and the halogen is electron withdrawing it would be expected that more of isomer B would form. This is indeed the case for 1b-d where more of isomer B is formed. It is only the odd case of 1a where more of isomer A is favored making fluorine differ from the other halogens when it comes to the Claisen rearrangement of allyl m-X-phenyl ethers. This could mean that, for the rearrangement, fluorine could possibly be better at donating its lone pair electrons to add electron density to the unhindered position. While ortho and para directing ability of the halogens might not be of high importance for the Claisen rearrangement it does show a similar trend as in nitration of halobenzenes. In nitration of fluorobenzene the nitro group is directed mostly to para position and in the Claisen rearrangement the allyl group migrates mostly to the unhindered position. In nitration of iodobenzene the nitro group is directed more to the ortho position than in nitration of fluorobenzene. This similar trend in Claisen rearrangement of allyl-m-halo-phenyl ethers and nitration of halobenzenes could be a coincidence but it could also suggest that electron density is distributed among the benzene in a similar way.

For 1e, the one with methyl as meta-substituent, isomer B is favored over isomer A. This is in agreement with previous results by White and Slater.18 However, the result found by Gozzo showed that the ratio was 1:1 which is slightly different from result observed in this experiment.12 This could mean that the percent of isomer A formed varies in range from 40-50%. For 1f, the one with ethyl as meta-substituent, isomer A is just slightly favored over isomer B. This could possibly mean that when alkyl group gets bigger the A:B ratio starts to get larger in favor of isomer A. For 1g the one with t-butyl as meta-substituent, isomer A is favored even more over isomer B, suggesting that when the alkyl group gets bigger, the A:B ratio increases in favor of A. For 1h, the one with phenyl, there was no significant difference in A:B ratio.

Figure 2.4: Inductive and resonance effect of alkyl group when attached to atom or sp2 or sp-hybridized carbon. The picture is reproduced from same picture from article from Luis Salvatella.20

Alkyl groups can be electron withdrawing by induction because of σ bond polarization when carbon is attached to any atom that is not more electronegative than carbon. When an alkyl group is attached to an sp2 or sp-hybridized carbon atom), a different behavior is observed because of electron density donation from alkyl C-H or C-C σ bonds to the empty p orbital of the contiguous atom(see Figure 2.4). Alkyl groups should be considered as atypical π- donor substituents because of lack of lone electron pairs. This is an example of 20 hyperconjugation. Alkyl groups are ortho para directing in electrophilic aromatic substitutions. In a study by Baas and Webster they found out that in nitration of substituted benzene, methylbenzene was better at directing to ortho position (34.5% para, 62.7% ortho), compared to ethylbenzene (47.2% para, 47.8% ortho).21 In another study by Sotheeswaran and Toyne they found out that t-Butylbenzene was much better at directing the reaction to para position (78.7% para, 10.6% ortho).22 The authors attributed this trend partially to steric hindrance. Phenyl group is related to vinyl group in terms of its electronic properties. It is considered to be inductively withdrawing because of the higher electronegativity of sp2 carbon atoms. It is also believed to be a resonance donating group because of its ability to donate electron density when conjugation is possible.23 Such a system as the biphenyl system is nonplanar with rotational freedom about the central carbon-carbon bond.24

So, the alkyl group are expected to be electron donating. While isomer A does not totally dominate over isomer B in the aromatic Claisen rearrangement when the meta-substituent is methyl or ethyl, they still do better than electron withdrawing halogens (apart from fluorine). When compared to nitration of alkylbenzenes a similar trend occurs as it did with the halobenzenes. Methylbenzene directs the nitro group better to the ortho position. In the Claisen rearrangement the allyl group migrates slightly more towards the substituted meta-

10 position. For ethylbenzene, the nitro group is directed almost equally to para and ortho positions. This is like the Claisen rearrangement with ethyl as meta-substituent where the allyl group favors the migration that forms isomer A just about over isomer B. When nitration of t-Butylbenzene is compared to the meta-substituted Claisen rearrangement with t-Butyl at meta-position a similar trend is observed. The nitration of t-Butylbenzene favors the para position while the rearrangement favors isomer A, both further away from the t-Butyl group. This could suggest that steric hindrance can influence the Claisen rearrangement. Previously by White and Slater, it had been concluded that steric hindrance was of no high importance in the reaction. The variation between isomers A:B for different meta-substituted phenyl ethers didn’t follow any systematic pattern with respect to the steric bulk of the substituents.25 For 1h, the one with phenyl group, a close to equal amount of isomers A and B is formed. When the biphenyl is unsubstituted the equilibrium torsional angle is 44.5° and the torsional barrier is 6.0 kJ/mol at 0°C temperature but gets slightly higher at 90°C or 6.5 kJ/mol. When substituents are added the barrier becomes higher.26 Steric hindrance might not be vital here because of the phenyl group’s ability to rotate about the central carbon-carbon bond.

Figure 2.5: Shows a possible scheme of the reaction in 1k.

Lastly, for 1i, 1j and 1k a diverse group was tested. These are trifluoromethyl, acetamido and alkoxy groups. The trifluoromethyl group has significant electronegativity that makes it inductively electron withdrawing.27 The acetamido group is an electron donating group because it has a lone pair of electrons that can activate the benzene ring. In electrophilic aromatic substitution it is ortho para directing. It is still a weaker donator than amine because of the presence of the electron withdrawing carbonyl group. For the alkoxy group the oxygen has a lone pair of electrons that are well placed to delocalize and increase the electron density within the ring through conjugation. However, the oxygen is also electronegative so it can be electron withdrawing by inductive effect.28 In this case the resonance effect dominates the inductive effect because the lone pairs of oxygen can be delocalized when oxygen is attached to conjugated system.

With the trifluoromethyl being electron withdrawing, it would be expected that more of isomer B would form than isomer A in 1i. This is in fact the case. Also, for 1j, the one with acetamido it would be expected for more of isomer A to form than isomer B. This is not the case as close to equal amount of isomer A and isomer B is formed. Still, 1j does better at forming isomer A when compared to the Claisen rearrangement with halogens as meta-

11 substituents (apart from fluorine). For 1k, the one with two alkoxy groups it would have been expected before the reaction that more than isomer A and isomer B could form. In Figure 2.5, two more isomers, C and D are thought to be able to form. However, after analyzing 1H NMR sample it was concluded that primarily isomers A and B formed. This particular reaction could possibly be studied further later. The A:B ratio is in favor of isomer A. This could be explained as before that the alkoxy group is electron donating. Steric hindrance might also have an effect here. As there are primarily two peaks observed in the 1H NMR analysis, only two products seemed to have formed, so it looks like when one allyl group starts to migrate the other one will not go as fast.

2.3 Meta- and para-substituted Allyl Phenyl Ethers

The results for meta- and para-substituted allyl phenyl ethers Claisen rearrangement are summarized in Table 2.3. In this part of the experiment, it was investigated how para- substituents would affect the ratio between the A and B constitutional isomers if the meta- substituent was kept constant, and what could possibly cause the reaction to favor one isomer over the other.

Table 2.3: A:B ratio results for meta- and para-substituted Claisen rearrangement. Sample Meta substituent Para substituent A:B product ratio* 1e CH3 H 1:1.20 2a CH3 F 1:1.30 2b CH3 Cl 1:1.65 2c CH3 CH3 1:1.20 2d CH3 iPr 1:1.30 2e CH3 SCH3 1:1.15 1b Cl H 1:1.40 3a Cl F 1:1.55 3b Cl Cl 1:2.30 3c Cl CH3 1:2.15 3d Cl CN 1:1.60

From the data given in Table 2.3, the first thing to report is that in all cases isomer B predominates over isomer A. Secondly when 1e, the one with only methyl as meta- substituent, is compared with 2a-e, only in the case of 2e is the A:B ratio lower in favor of isomer B. The ratio increases slightly for 2a and 2d and it increases significantly in the case of 2b. Interestingly in the case of 2c, the one with methyl group both as para- and meta- substituent, the A:B ratio stays the same as in 1e.

When 1b, the one with chlorine as meta-substituent is compared to 3a-d the A:B ratio increases in all cases. An interesting phenomenon occurs with 2a and 2c on the one hand and 3a and 3c on the other hand. In the case of 2a, the one with fluorine in para position and methyl in meta position, it makes more of isomer B than 2c, the one with methyl both in meta and para position. This is flipped on its head when the meta-substituent is chlorine. In the case of 3a, the one with fluorine in para position and methyl in meta position, it makes less of isomer B than 3c, the one with methyl in para position and chlorine in meta

12 position. The results from para- and meta-substituted Claisen rearrangement suggest that para-substituents do influence the A:B ratios but not only that, it also suggests that the function of the substituent might change or be slightly altered when it interacts with other groups.

Previously, in section 2.2 the subgroups had been defined as either electron withdrawing or donating. Electrophilic substitution of benzene like nitration of benzene was used as reference. Not because the reaction is like the Claisen rearrangement mechanistically, it is not, but because in both cases the substituent is attached to a benzene ring and the behavior of the substituent is expected to be similar. The halogens were defined as electron withdrawing and the methyl group was defined as donating. Starting with the isopropyl group, it is expected to behave like other alkyl groups, and in fact Remya and Suresh found out that it is slightly electron donating when attached to benzene.29 The thioether is expected to be electron donating through resonance.30 Finally, the last group to define is the cyano group. The cyano group has been described as electron withdrawing both by inductive effect and resonance.31

Another thing to take from electrophilic aromatic substitution is when there are two substituents that might either cooperate or compete. The site at which a new substituent is introduced depends on the orientation of the two groups attached to the benzene ring and their individual directing effects. In electrophilic aromatic substitution it has been found out that when two substituents are ortho to each other and they are both either electron donating or electron withdrawing they tend to be non-cooperative. On the other hand, when the two substituents are ortho to each other and one is donating and the other withdrawing they tend to be cooperative.

Here it is important to remember that the Claisen rearrangement is a mechanistically different reaction. From the meta-substituted Claisen rearrangement it has been found out that meta-substituents do affect the regioselectivity of the reaction. As a thought experiment, one can consider the case where there was only a para-substituent on the allyl phenyl ether. Because of its symmetry, isomers A and B would be the same. Here there is meta- and para- substituted Claisen rearrangement and it raises a couple of questions. For starters, how do different meta- and para-substituents affect each other, or even when the meta- and para- substituents are the same, how do they affect each other? Does the substituent show different behavior in para position than it would in meta position?

When sample 2a is analyzed, the methyl group is expected to be electron donating and the fluorine group is expected to be withdrawing. In previous results for 1e, where there was only methyl as meta-substituent, the A:B ratio was 1:1.20. Here in 2a the ratio is 1:1.30 so it looks like fluorine amplifies the regioselectivity to the same side as was preferred in 1e. In 2b, the one with methyl as meta-substituent and chlorine as para-substituent, the A:B ratio increase even more in favor of isomer B. In 2c, the one with methyl in both meta and para position the A:B ratio is the same as in 1e. One explanation could be that when methyl is in para position with another donating group like itself it does not influence or work together with the meta group. This would be in contrast with reaction 3c, when methyl group is in para position with the electron withdrawing chlorine in meta position, where the A:B ratio increases a lot in favor of isomer B.

Overall, in reactions 2 where the methyl is meta-substituent and there are various para- substituents it looks like when the para group is electron withdrawing like chlorine more of

13 isomer B will form. Hence, electron withdrawing group in para position could amplify the regioselectivity of the methyl group when it is in meta position. When the para-substituents is electron donating like methyl, isopropyl or the thioether, the ratio barely changes. Hence, electron donating groups do not seem to have much influence on the methyl group when it is in meta position. The A:B ratio gets slightly higher in favor of isomer B when the group is isopropyl, and it goes slightly down when the group is thioether.

When sample 2a is analyzed, the methyl group is expected to be electron donating and the fluorine group is expected to be withdrawing. Previous results in 1e where there was only methyl as meta-substituent there was A:B ratio of 1:1.20. Here in 2a the ratio is 1:1.30 so it looks like fluorine amplifies the regioselectivity to the same side as was preferred in 1e. In 2b, the one with methyl as meta-substituent and chlorine as para-substituent, the A:B ratio increase even more in favor of isomer B. In 2c, the one with methyl in both meta and para position the A:B ratio is same as in 1e. One explanation could be that when methyl is in para position with another donating group like itself it does not influence or work together with the meta group. Because in reaction 3c when methyl group is in para position with the electron withdrawing chlorine the A:B ratio increases a lot in favor of isomer B.

Overall, in reactions 2 where the methyl is meta-substituent and there are various para- substituents it looks like when the para group is electron withdrawing like chlorine more of isomer B will form. Hence, electron withdrawing group in para position could amplify the regioselectivity of the methyl group when it is in meta position. When the para-substituents is electron donating like methyl, isopropyl or the thioether, the ratio barely changes. Hence, electron donating groups do not seem to have much influence on the methyl group when it is in meta position. The A:B ratio gets slightly higher in favor of isomer B when the group is isopropyl, and it goes slightly down when the group is thioether.

One last point to point out is that it is interesting to speculate with case 2d, the one with isopropyl in para position. For reactions 1f and 1g, the ones with ethyl and t-Butyl as meta- substituents respectively, the A:B ratios were 1:0.90 and 1:0.40. And in the case of 1a, the one with fluorine, the A:B ratio is 1:0.60. Since 2a and 2d have the same A:B ratio in para- and meta-substituted rearrangement maybe a meta-substituted rearrangement with isopropyl as meta-substituent would have the same A:B ratio as 1a.

Now in the cases where chlorine is the meta-substituent a similar trend can be seen in A:B ratios where isomer B is favored, that is 1a < 1e < 1b is the same as 3a < 3c < 3b. Fluorine from para position seems to amplify the preference of isomer B formation of both when methyl is in meta position and when chlorine is in meta position. Chlorine shows similar behavior as fluorine when it is in para position in the regard that it seems to amplify the isomer preference of the meta-substituent. It amplifies the A:B ratio in favor of isomer B in both cases, 2b and 3b. A different behavior is observed when 3c, the one with methyl in para position and chlorine in meta position, is compared to 2c, the one with methyl in both para and meta positions. Finally, in the case of 3d the cyano group is expected to be electron withdrawing but the isomer A or isomer B directing ability in meta-substituted Claisen rearrangement is not known. It gives similar ratios to 3a but an explanation for this is not apparent at this moment.

A final thought on the matter is that the direction effect of the para substituent might change dramatically both because it is in a different position than if it would be the meta- substituent and also because there is another group in the meta position and these two groups

14 could be having some effect on each other. This is very hard to rationalize with such a small sample pool. Remember, both methyl and chlorine group directed the allyl group towards forming more of isomer B rather than isomer A in the meta-substituted Claisen rearrangement. Here it would be suggested to have a larger sample size of reactions where another group than methyl or chlorine would be picked to be as the constant meta- substituent. A group that would direct meta-substituted Claisen rearrangement to form more of isomer A than isomer B would be useful, such as F.

2.4 Theoretical calculations

2.4.1 Reaction energies

The ground-state optimized geometry of reactants, transition states and intermediates were all calculated at the B3LYP/def2-TZVP level of theory. The selected reactants, transition states and intermediates are given in Figure 2.6. The selected B3LYP tends to give good results when calculating organic molecules.32 This theoretical level was also used for frequency calculations. The calculations were performed to see if the favored products from experiments correlate with theoretical calculations of kinetically and thermodynamically favored Claisen rearrangement products. For these calculations, a handful of samples were selected each carrying the same sample name as in Result and Discussion sections 2.1 through 2.3.

Figure 2.6: Scheme where the transition state and intermedidates are defined for computer calculations.

Table 2.4 summarizes the Gibbs free energy calculated for reactants, the activation energies for isomers A and B, and for the corresponding intermediates for products A and B. All calculations were carried out with the orca package.

15 Table 2.4: Calculated Gibbs free energies for reactants and the relative energies to reactants of transition states for isomers A and B (TS A and TS B, respectively), and intermediates for isomer A and B (IA and IB, respectively) where the energy for reactant is in Hartrees and the relative energies are in kcal/mol. The table also shows energy differences between A and B transition states and intermedidates for each reaction.

Sample GR TS A TS B ΔTS IA IB ΔI 1a -523.2 31.1 33.9 -2.8 8.3 9.6 -1.3 1b -883.5 30.4 29.6 0.8 9.1 8.4 0.7 1c -2997.4 31.1 30.3 0.8 9.5 7.2 2.3 1e -463.3 30.7 30.3 0.4 8.2 8.8 -0.6 1f -502.5 31.2 30.2 1.0 6.4 11.6 -5.2 1i -761.0 30.4 29.1 1.3 10.6 9.0 1.6 2a -562.5 31.2 31.6 -0.4 8.9 8.3 0.6 2b -922.8 30.6 29.9 0.7 7.8 7.6 0.2 2c -502.5 30.8 30.6 0.2 7.9 8.0 -0.1 3a -982.8 30.1 29.1 0.2 7.3 6.5 0.8 3b -1343.1 31.5 30.0 1.5 10.4 8.9 1.5 3c -538.5 31.2 30.1 1.1 9.2 8.7 0.5

Starting with 1a, the one with fluorine as the substituent, IA is both kinetically and thermodynamically favored over IB. For 1b, the one with chlorine as substituent, IB is both kinetically and thermodynamically favored over IA. For 1c, the one with bromine as substituent, IB is both kinetically and thermodynamically favored over IA. This agrees with the available experimental data from section 2.1. When 1b is compared to 1c the difference between energies of TSA and TSB in 1b is 0.8 kcal/mol and for IA and IB it is 0.7 kcal/mol. For 1c the difference between transition states and A and B is 0.8 kcal/mol and for IA and IB it is 2.3 kcal/mol. This could suggest that when the ratio of IA and IB grows larger the energy difference between IA and IB also grows larger.

For 1e and 1f, the ones with methyl and ethyl as substituents respectively, the calculations suggest in both cases that IA is thermodynamically favored. This would agree with the statement that aromatic Claisen rearrangements with electron donating meta-substituents would favor formation of isomer A. However, interestingly, in both cases of 1e and 1f, isomer B is kinetically favored over isomer A. This could explain why more of isomer B forms in case of 1e and why the A:B ratio is 0.9:1 in case of 1f. When 1f is compared to 1a it is noticed from experimental data that the A:B ratio is 1:0.6 for 1a and 1:0.9 for 1f. It can be seen from theoretical calculations that the difference between IA and IB is 1.3 kcal/mol for 1a and 5.2 kcal/mol for 1f. It is also observed that theoretically IA is more stable for 1f than 1a. This could mean that the kinetic product of 1f is getting in the way of a better A:B ratio in favor of isomer A.

It is not unheard of that kinetic products can predominate thermodynamic products. Here are examples from two mechanistically different reactions (see Figure 2.7). Starting with addition of HBr to 1,3-butadiane. When HBr is added to 1,3-butadiane it forms a mixture of 3-bromo-1-butene and 1-bromo-2-butene. At -80°C, 3-bromo-1butene is the major product but at 40°C 1-bromo-2-butene is the major product. Theoretical calculations showed that 1- bromo-2-butene was thermodynamically more stable than 3-bromo-1-butene.33,34 In the second example the sulfonation of naphthalene is explored. When the reaction is run at 80°C, 1-naphthalenesulfonic acid is the major product, at 160°C, 2-naphthalenesulfonic acid is the

16 major product. Theoretical calculations showed that 2-naphthalenesulfonic acid is more stable than 1-naphthalenesulfonic acid.35

Here it has been shown that temperature is of high importance when carrying out reactions regarding to kinetic and thermodynamic control of the reaction. The aromatic Claisen rearrangement for 1e was carried out at 200°C which should be enough energy to overcome the energy barrier of both species. But given that the kinetic product seems to have prevailed, the question remains whether higher temperatures would have yielded more of the thermodynamic product of 1e.

For 1i, the one with trifluoromethyl as meta-substituent the theoretical calculations predict isomer B to be kinetically favorable and the intermediate of isomer B to be thermodynamically favorable. This agrees with experimental results where more of isomer B formed than isomer A. When 1i is compared to 1b and 1c, the ones with chlorine and bromine as meta-substituents, the A:B ratios are 1b < 1i < 1c in favor of isomer B. When the energy difference between IA and IB is calculated a similar trend is observed that 1b < 1i < 1c. This could be a coincidence and would have to be studied further with a larger sample pool but from these results there is a possibility that one could use theoretical calculations to estimate when comparing two reactions which one would give better A:B ratios towards either A or B by using energy difference between IA and IB. This would then probably have to be for reactions where the product is both kinetically and thermodynamically favorable.

With 2a, the IB is predicted to be more thermodynamically stable than IA, but the IA is predicted to be more kinetically favorable than IB. Here it is a bit different from the case of 1e, where the possibility of the kinetically favoured intermediate IB was intervening with the thermodynamically favoured intermediate IA, because the A:B ratio was 1:1.20. Because for 1e it is predicted that thermodynamically, more of isomer A should form than B, but the experimental data show that more of isomer B forms, the possibility was entertained that the temperature needed to be higher. In 2a there seems to be success driving the reaction at 200°C to get the more thermodynamically favoured intermediate IB even if IA is predicted to be kinetically favoured. This could suggest that the temperature at which kinetic control gives way to thermodynamic control can vary significantly for different substrates in the Claisen rearrangement.

For 2b, it is predicted that the intermediate for product isomer B is both thermodynamically and kinetically favoured and agrees with experimental data that show that isomer B is favoured over isomer A. An interesting thing to point out is that the energy differences between both transition states and intermediates can be somewhat smaller when there are meta- and para-substituents than if there was only meta-substituent. For example, the energy difference between the intermediates in 1e is 0.6 kcal/mol but for 2b it is only 0.2 kcal/mol.

In 2c, the same thing happens as in 1e. Isomer B is kinetically more favoured while isomer A is thermodynamically favoured. As said before, 2c and 1e have identical ratios. Before, it was pointed out that the energy difference between transition states and the intermediates is smaller for meta- and para substituted Claisen rearrangement than if it were only meta- substituted Claisen rearrangement. Here the energy difference between both transition states A and B, and intermediates A and B is very small.

When samples 3a-3c are analysed, for all three reactions, isomer B is predicted to be both kinetically and thermodynamically favoured. This agrees with experimental data. The energy difference between transition states A and B for 3a is 1 kcal/mol, for 3b it is 1.5 kcal/mol and for 3c it is 1.1 kcal/mol. The energy difference between IA and IB is 0.8 kcal/mol for 3a, 1.5 kcal/mol for 3b, and 0.5 kcal/mol for 3c. The energy difference between transition states follow the same trend as A:B ratios in favour of isomer B between these 3 reactions where 3a < 3c < 3b. However, there is not much difference between the two energy differences of 3a and 3c when it comes to the intermediates.

Overall, the energy calculations of reactant, transition states and intermediates of the products of isomers A and B seem to be in good agreement with experimental results. Furthermore, beforehand it was expected that more of isomer A would form for 1e and 1f but the calculations suggest that the transition state for IB is lower in energy than the transition state for IA for both 1e and 1f and this could maybe answer why there is not more of isomer A seen than isomer B in 1e and why the A:B ratio is not bigger in favour of isomer A for 1f.

2.4.2 Population analysis and atomic charges

The molecular electrostatic potential (MEP) map was created of molecules. The MEP is created by its nuclei and electrons and is related to electron density. It can hold significance because it provides insight into the sites within the molecule where the electron distribution effect is dominant.36 However, when analyzing the MEP of the reactant molecules in the Claisen rearrangement most of them showed the same electrostatic potential as in Figure 2.8 (b). The molecule in Figure 2.6 (b) is the reactant in 1b, the one with chlorine as meta- substituent. In Figure 2.8 (b) the red color is towards increasing range of potential while the blue color is towards decreasing range of potential. Green regions are of intermediary potential. In Figure 2.8 (b) it can be seen that the regions that take part in the reaction are of higher potential than other regions. However, it is very difficult to see which region is more negative. To find out the effective atomic charges a population analysis was performed for the molecules.

Figure 2.8: (a) Optimized structure of reactant in 1b, (b) MEP of the optimized structure of reactant in 1b.

Calculations of effective atomic charges is significant when quantum calculations are applied to molecular systems. In such systems, the atomic charges are attributed through population analysis. To study the electrostatic arguments that could explain possible differences in the potential of the reaction sides in the Claisen rearrangement, the atomic charges of reactants were determined with Mulliken population analysis (MPA), the Hirshfeld population analysis (HPA), the Löwdin population analysis (LPA), and the natural population analysis (NPA) at HF/def2-SV(P) level of theory.37 Here the aim is not to compare the different population analysis methods or to find the exact atomic charges of the molecule. But much rather to see if they show similar trend. It needs to be pointed out that results from atomic charge calculation need to be carefully interpreted as equating electrostatic potential with atomic charges is not always valid procedure.38

The atoms of most interest are illustrated in Figure 2.8 (a), the atoms are given a number from 1 and 9. In Figure 2.9 the atomic charges for reactants in the meta-substituted Claisen rearrangement is reported, the table for the graphs in Figure 2.9 can be found in Appendix A. The reactants get same label as in Table 2.1.

From the data observed in Figure 2.9 the main trend is that there is a difference in atomic charges of carbon 1 and 3. Furthermore, for carbon 5 it is predicted to be negative just like carbon 1 and 3. However, when the atomic charges of hydrogen 6 and 7 are added up that region has a slight positive charge overall in most cases.

Figure 2.9: Graph of atomic charges from MPA, LPA, HPA, NPA for the reactants from 1a- c, 1e-f, and 1i. The X-axis shows the atoms that atomic charges were calculated for. The Y- axis shows the calculated atomic charges.

Starting with 1a, the one with fluorine as meta-substituent, carbon 1 is predicted to have higher negative atomic charge in LPA and HPA than carbon 3 but in MPA and NPA it is carbon 3 that has higher negative atomic charge than carbon 1. When hydrogen 2 and 4, the ones attached to carbon 1 and 3, respectively, are considered the overall charge in the region is still negative. All models predict carbon 5 which is on the allyl group to be negative with two positively charged hydrogen attached to it. If the positive charges are taken into account, the overall charge region of carbon 5 and hydrogen 6 and 7 is positive. This could help with the attraction in the reaction, but it is also difficult to say how much influence the positive hydrogen have on the reaction side. LPA predicts the fluorine group to have a positive charge while HPA predicts it to have negative charge of -0.15 Hartree. MPA and NPA predict the fluorine to have negative charges of -0.32 and -0.34 Hartree, respectively.

20 For 1b, the one with chlorine as meta-substituent, all population analysis methods predict carbon 3 to have higher negative atomic charge than carbon 1. This would correlate well with the fact that in the meta-substituent Claisen rearrangement where chlorine is the meta- substituent, more of isomer B forms rather than isomer A. When hydrogen 2 and 4 are considered the reaction regions on the benzene ring still has overall negative charge where the region around carbon 3 is more negative than around carbon 1. Just like before with 1a, all population analyses predict for 1b that carbon 5 is negatively charged with positively charged hydrogen attached to it. Again, when the charges are added up, this region on the allyl group is slightly positive. LPA predicts the chlorine group to be positively charged, but less positive than fluorine group. MPA, HPA and NPA predict the chlorine group to be negatively charged but in all cases less negatively charged than fluorine.

With 1c, the one with bromine as meta-substituent, all population analysis methods predict carbon 3 to have a higher negative atomic charge than carbon 1. When the charges of the hydrogen attached to carbon 1 and 3 are considered the overall charge in these regions is still negative where the region around carbon 3 dominates over carbon 1. All population analysis predict carbon 5 to be negatively charged with positive hydrogen attached to it where the overall charge in this region gets slightly positive. MPA predicts the bromine group to be less negative than the chlorine group, so the order of negative charges on meta-substituents F, Cl, Br would be F > Cl > Br where fluorine is the most negatively charged. LPA predicts the bromine group to be positive but less positive than the chlorine group so the order of positive charges on meta-substituents F, Cl, Br would be F > Cl > Br where F is the most positive. HPA pretends the order to be Br > F > Cl where bromine is the most negatively charged while NPA predicts fluorine and chlorine to be negatively charged and the bromine to be positively charged, but the order is F > Cl > Br.

For 1e, the one with methyl as meta-substituent, all population analysis methods predict carbon 3 to have a higher negative atomic charge than carbon 1. When the atomic charges of the hydrogen attached to carbon 1 and 3 are considered the overall charges in these regions is still negative where the region around carbon 3 dominates over carbon 1. The charge on carbon 5 is negative with the charges of hydrogen attached to it being positive. When the charges of these three atoms are added up the region has overall slightly positive charge. The carbon in the methyl group has a negative charge but when the charges of hydrogen are added to the group, the MPA, LPA and NPA predict the group to be slightly positive while HPA predicts it to be slightly negative.

Finally, for 1i, the one with trifluoromethane as meta-substituent, the population analysis methods predict that carbon 3 to have higher negative atomic charge than the carbon 3. When the atomic charges of the hydrogen attached to carbon 1 and 3 are considered the overall charge in the region is still negative where charges in the region of carbon 3 predominates

21 over carbon 3. Like before the carbon on the allyl group is negative with two positive hydrogen attached to it where the overall charge gets positive. MPA, LPA and NPA predict the trifluoromethane meta-substituent to be overall positive while HPA predicts it to be slightly negative.

Overall, the results from population analysis of meta-substituted Claisen rearrangement seem to suggest that the carbon on the benzene ring that forms the new carbon-carbon bond to give more of one isomer has higher negative charge than the carbon that forms the new carbon-carbon bond to give the lesser isomer. For example, in 1f there is higher negative charge on carbon 1 than carbon 3 and in the experiment more of isomer A formed than isomer B. In 1c there is higher negative charge on carbon 3 than carbon 1 and in the experiment more of isomer B formed than isomer A. Only in 1a does the population analysis fail to be consistent with each other about this, where MKA and NPA say that carbon 3 has a higher negative charge than carbon 1 and LPA and HPA say that carbon 1 has a higher negative charge than carbon 3. In the experiment more of isomer A formed for 1a, than isomer B.

Following is the report of population analysis done at selected para- and meta-substituted reactants in Claisen rearrangement. In Figure 2.10 selected para- and meta- substituted reactants where methyl is constant as meta-substituent are reported. They take the same sample names as in Table 2.3. Note that 1e is reported again, here just for reference. In Figure 2.11 selected para- and meta- substituted reactants where chlorine is constant as meta-substituent are reported. They take the same sample names as in Table 2.3. Here 1b is reported again just for reference. The tables for all the graphs in Figure 2.10 and Figure 2.11 can be found in Appendix A.

22 Starting with 2a, the one with methyl as meta-substituent and fluorine as para-substituent, all population analysis methods predict carbon 3 to have higher negative charge than carbon 1. When hydrogen are taken into account the region is still negative where the region around carbon 3 is more negative than carbon 1. Same as before, carbon 5 on the allyl group is negative with two positive hydrogen attached to it. The overall charge in that region is positive. Here all population analysis methods predict the methyl group, the meta-substituent to have positive charge overall while the para substituent, fluorine, has negative charge.

For 2b, the one with methyl as meta-substituent and chlorine as para-substituent, all population analysis methods predict carbon 3 to have higher negative charge than carbon 1. The region around the carbon 1 and 3, after when the charges of hydrogen have been taken into account, still express negative charge. The carbon on the allyl group is negative with two positive hydrogen an attached to it. The methyl group has positive charge overall, while the chlorine has negative charge. When 2a and 2b are compared chlorine has much less negative charge than fluorine as para-substituents.

For 2c, the one with methyl both as meta- and para-substituents, all population analysis methods predict carbon 3 to have higher negative charge than carbon 1. For the attached hydrogen the same trend as before is observed. Same for the carbon and its hydrogen on the allyl group. Both methyl groups in meta and para position show positive charge and in fact they show very similar charges.

Figure 2.11: Graph of atomic charges from MPA, LPA, HPA, NPA for the reactants from 1b, and 3a-c. X-axis the atoms that atomic charges were calculated for. Y-axis shows atomic charges.

23 For 3a, the one with chlorine as meta-substituent and fluorine as para-substituent, all population analysis methods predicted carbon 3 to have higher negative charge than carbon 1. The same trend as before is observed that the hydrogen attached to the carbon are positive but the overall charge in the region of carbon 3 and 1 is negative. For the carbon on the allyl group it is still predicted to be negative with positive hydrogen. Now both chlorines as meta- substituent and fluorine as meta-substituent are predicted to be negative. In MPA and NPA the chlorine is predicted to be less negative for 3a than it is in 1b. In HPA it is predicted to be more negative. Fluorine as para-substituent in 3a is predicted to be slightly less negative than fluorine as para-substituent in 2a.

With 3b, the one with chlorine as both meta- and para-substituent, all population analysis methods predicted carbon 3 to have higher negative charge than carbon 1. Hydrogen attached to carbon 1 and 3 are positive but the overall charge in the region is negative where carbon 3 has higher negative charge than carbon 1. It is still same with allyl group where carbon 5 has negative charge but the two hydrogen attached to it have positive charge. MPA predicts chlorine to have less negative charge in 3b than in 1b. It still has slightly more negative charge than 3a. The order is 1b > 3b > 3a. In HPA and LPA the charges of chlorine both in meta and para position are positive but also like in 2c where methyl was both in meta and para position, the magnitude of the charges is very similar.

For 3c, the one with chlorine as meta-substituent and methyl as para-substituent the same trend as before was observed with carbon 1 and 3 where carbon 3 is more negative. The hydrogen attached to carbon 1 and 3, and carbon 5 and its hydrogen also follow the same trend.

When comparing 2b, 2c, 3b, and 3c both methyl and chlorine as meta-substituent have less positive or higher negative charge when methyl is the para-substituent instead of chlorine as para-substituent. When chlorine is in para position it has more negative charge when methyl is in meta position instead of chlorine in meta position. And when methyl is in para position it is has more positive charge when methyl is in meta position instead of chlorine.

When 1e, 2a, 2b, and 2c are compared there is a little disagreement that vary within the population analysis methods when it comes to the meta substituent. In MPA, 2b has the highest positive atomic charge while 1e has the lowest. The order is 2b > 2a > 2c > 1e. In NPA 2c has the lowest charge while 2b has the highest charge. The order is 2b > 2a > 1e > 2c. These two correlate somewhat with the A:B ratio which is 2b > 2a > 2c = 1e in favour of isomer B.

In an attempt to understand the atomic charges on carbon 1 and 3 better, a plot was made of the atomic charge difference on carbon 3 and 1 versus the B:A product ratio. One such graph is reported here in Figure 2.12a for HPA where there appears to be correlation between the charge difference on carbon 3 and carbon 1 and the A:B ratio. The graph shows that when carbon 1 has higher negative charge than carbon 3, more of isomer A will form. When carbon 3 has higher negative charge than carbon 1, more of isomer B will form. One thing to point out is that the slope where more of isomer B forms is not that high. In Figure 2.12b the same plot is made but this time for NPA, just for comparison. There it can been seen that the 1f is a bit of an outlier but nevertheless, for the other materials there seems to be some correlation. So, it does look like the substituents affect the density on the reaction side.

24 The MEP gives a good idea about the reaction sides of the allyl phenyl ether. Both carbon 1 and 3 look to be reactive towards the allyl group. The general results from population analysis seems to suggest that the carbon on the benzene ring that makes the new carbon- carbon bond of the isomer that forms more of is of higher negative charge than the carbon that makes the new carbon-carbon bond of the isomer that forms less off. So, there is a possibility that regioselectivity of the Claisen rearrangement could have a electrostatic driving force.

2.4.3 Molecular orbital analysis

The transition state of the Claisen rearrangement of allyl vinyl ether it can be described as proceeding through intramolecular HOMO (O-vinyl moiety) and LUMO (allyl moiety) orbital interactions through the resonance of the π-electron system. Gozzo and co-workers found out that when the vinyl group is switched out for aryl group the complexity of the system greatly increases.12 They concluded that a simple frontier HOMO-LUMO orbital interaction could not be used to predict reactivity or regioselectivity by mimicking the orbital interactions of TS for aromatic Claisen rearrangement.

This effect is illustrated in Figure 2.13b when allyl vinyl ether and allyl aryl ether with methyl as meta-substituent were compared by Gozzo and co-workers. For the allyl vinyl ether (left), the LUMO has contributions from the antibonding π orbitals on the allyl group. But when there is allyl aryl ether (right) the LUMO only seems to have contribution from the antibonding π orbitals on the aryl group. There seems to be no contribution from the antibonding π orbitals on the allyl group itself. The problem Gozzo and his co-workers had was that when π-orbital-containing substituents were added to the aryl group, the system became more complex and any resembles of HOMO-LUMO interactions disappeared.

25 In their calculations, Gozzo and his co-workers used Pople basis set. Here it will be switched to Karlsruhe like in calculations of reaction energies and these calculations will be performed at B3LYP/def2-SV(P) level of theory. The atoms of interest in HOMO and LUMO orbitals are labelled in Figure 2.13a.

Another problem that can rise is when the molecular orbitals are studied visually only qualitative conclusions can be drawn. This can be a big problem when two almost identical systems are compared. For example, in Figure 2.14a the HOMO and LUMO of 1a are compared to Figure 2.14b the HOMO and LUMO of 1e. As it can be seen there is not much difference between the two molecules when they are qualitative compared. So, for the analysis of selected reactants in the Claisen rearrangement, there will be used molecular orbital composition analysis. The advantage of composition analysis is that the results can be quantified instead of just being qualitative analysed.

1a 1f 1e 2a 1i HOMO Carbon 1 17.35 14.03 11.55 10.93 9.36 Carbon 2 14.06 15.27 15.27 15.43 14.78 Carbon 3 5.08 7.87 10.00 8.74 13.52 Carbon 4 1.11 1.27 1.83 0.17 1.91 Carbon 5 0.22 0.25 0.16 0.45 0.89 LUMO

26 Carbon 1 6.19 9.00 8.30 15.45 18.03 Carbon 2 2.78 9.04 3.88 16.38 5.82 Carbon 3 5.90 6.96 12.14 18.85 18.86 Carbon 4 21.46 17.67 13.47 2.19 0.47 Carbon 5 25.35 20.15 15.48 2.67 0.26

In Table 2.5. the results from Hirshfeld molecular orbital analysis of HOMO and LUMO can be seen for reactants from 1a, 1f, 1e, 2a and 1i. The results from other reactants like with chlorine and bromine as meta-substituent were discarded as it seems like when the atoms get heavier the calculations for composition of LUMO on carbon 4 and 5 disappear. 2a and 1i are example of this because they are little bit more complex systems than 1a, 1f, 1e. There it can be seen that there is no composition on carbon 4 and carbon 5, the ones on the allyl group. They are still reported here because the trend of carbon 1 and 3 on the aryl group looks to be in agreement with experimental data.

Figure 2.14: (a) HOMO of 1a, (b) Shows LUMO of 1a, (c) HOMO of 1e, (d) Shows LUMO of 1e

27 The first thing to report is that the coefficient on carbon 1 is always larger than the coefficient on carbon 3 bar in the case of 1f. The A:B ratio in favour of isomer B for the selected reactants is 1a < 1f < 1e < 2a < 1i. The coefficient on carbon 1 for the selected reactants is 1a > 1f > 1e > 2a > 1i. For carbon 3, for reactants 1a, 1f and 1e the coefficient gets larger with the order 1a < 1f < 1e which correlates with the A:B ratio in favour of isomer B.

Gozzo and his team had previously struggled with finding coefficients on carbon 4 and carbon 5 on the allyl group even for a reactant with methyl as meta-substituent like in 1e. Here it has been shown by improved computational and improved basis sets that a coefficient can be obtained on carbon 4 and 5 and hence there is a suggestion that the aromatic Claisen rearrangement has the same reaction mechanism as the classical Claisen rearrangement. Furthermore, here the coefficient on both carbon 4 and carbon 5 seems to get smaller in the order 1a > 1f > 1e which correlates with the A:B ratio from these reactions.

However, when the systems start to get more complex beyond the one with the ethyl group, the B3LYP/def2-SV(P) doesn’t predict that there is a coefficient on carbon 4 and 5 or that it is a much smaller than in examples of 1a, 1f, and 1e.

Overall, the results from 1a, 1f, and 1e look promising because there is a trend that the coefficient gets larger on carbon 3 as more of isomer B starts to form. But the coefficient is still smaller on carbon 3 than on carbon 1 in 1e where more of isomer B forms than isomer A. This could possible mean that the size of the occupancy from the molecular orbital on carbons 1 and 3 is not predominant for the regioselectivity of aromatic Claisen rearrangement but with the trend observed from 1a, 1f and 1e it could still have some role to play. Another possible explanation is that with computer calculations the meta-substituent could be getting in the way of the molecular orbital occupancy on the carbon 3.

When the system gets more complicated the results for carbon 4 and 5 are not like one would have hoped beforehand. Here is a question if another level of theory like coupled cluster and another basis sets like Dunning basis sets could yield different or even better results.

28 3 Conclusions

The meta-substituted aromatic Claisen rearrangement has been studied further. The previous results had concluded that the regioselectivity depended roughly on the electronic nature of the meta-substituent. If the meta-substituent were electron donating the allyl group would migrate to the unhindered position to form isomer A. If the meta-substituent was electron withdrawing the allyl group would migrate towards the meta-substituent to form isomer B.

This research does support this conclusion to certain extent. Here there are reported two cases where this does not hold up. In the first case, 1a, where fluorine is the meta-substituent and it is expected to be electron withdrawing, more of isomer A forms rather than isomer B. In case of 1e, where methyl is the meta-substituent and it is expected to be electron donating, more of isomer B forms rather than isomer A.

Theoretical calculations of reaction energies were however in agreement with the experimental results for 1a. The calculations predicted that both transition state of isomer A and intermediate for isomer A would be lower in energy than of isomer B. In the case of 1e the intermediate of isomer A is predicted to be lower in energy than isomer B which disagrees with experimental results. However, the transition state of isomer B was lower in energy than of isomer A for 1e. This could mean that the reaction needs to be carried out at higher temperature.

For meta- and para-substituted aromatic Claisen rearrangement there were two different series of rearrangements tried out, one with methyl as meta-substituent with various para- substituents and the other with chlorine as meta-substituent with various para-substituents. The main results here were that just like in the meta-substituted aromatic Claisen rearrangement where methyl and chlorine were the meta-substituents, isomer B was also always favored in the meta- and para-substituted aromatic Claisen rearrangement. Different para-substituents did affect the A:B ratio in both cases. In most cases it amplified the A:B ratio in favor of isomer B. Unfortunately, both methyl and chlorine preferred isomer B as when they were meta-substituents. It would have been interesting to find a group that favors the formation of isomer A to try out in the future.

The theoretical calculations for meta- and para-substituted aromatic Claisen rearrangement agreed in most cases that the isomer that formed more of was thermodynamically more stable than the other. Only in case 2c was isomer A predicted to be slightly more thermodynamically stable. The difference between isomer A and isomer B in case of 2c was 0.1 kcal/mol. However, for the same sample, the transition state of B is predicted to be slightly lower in energy or of 0.2 kcal/mol. Again, suggesting that maybe the temperature needed to be a bit higher in some cases!

Population analysis was done with MPA, LPA, HPA and NPA. Here the aim was not to find the exact atomic charge on selected atoms but only to check if a similar trend would be observed between different population analysis. In most cases the population analysis gave same results, that the carbon on the aryl ring that is involved in the rearrangement to form more of one isomer has higher negative charge than the carbon on the aryl ring that forms

29 less isomer. However, there was an instance, with fluorine, where two theories did not agree with these results, MPA and NPA, leaving the question if this could be tested more with other methods, like CHELP-G for example. Plotting difference in HPA charges between carbon 1 and carbon 3 versus B:A ratio show there is some correlation between atomic charges and the isomer that predominates suggesting that the substituents influence the reactivity on the carbon on the aryl ring that take part in the new carbon-carbon forming during the Claisen rearrangement.

Finally, previously Gozzo and his co-workers had tried to calculate HOMO and LUMO for reactant 1e, but without seeing any coefficients on the carbon on the allyl group in LUMO. By improving on basis sets and using Hirshfeld molecular orbitals composition analysis, here were reported three reactants: 1a, 1f, and 1e, that showed that there are orbitals on the allyl carbon in the LUMO. Furthermore, a trend was observed where the coefficient on carbon 1 gets lower and coefficient on carbon 3 gets higher as the A:B ratio increases in favor of isomer B.

Unfortunately, attempts of calculations with more complicated systems proved difficult. With heavier atoms like chlorine and bromine the same results of coefficient on the allyl carbon were not observed. It seems like when the system gets larger and more complicated these calculations struggle within B3LYP/def2-SV(P) level of theory. An interesting task for the future would be to try it within coupled cluster level of theory and with Dunning basis sets.

For what appears to be just a simple rearrangement it appears that the aromatic Claisen rearrangement still has some investigating left to do. Meta- and para-substituted aromatic Claisen rearrangement could be studied further with more variant in the meta-substituents than just chlorine and meta. Then there is another aromatic system that could be studied, an allyl phenyl ether with two meta-substituents. Finally, while theoretical calculations do look promising, they could be improved further upon. For frontier orbitals there still is some work needed to be done to see if calculations can successfully agree with experimental data when the system are complicated and have heavier atoms. Finally, the conformation of the allyl group was not specially investigated. It could be interesting to investigate how different alignments of the allyl group can influence the molecular orbitals or even atomic charges.

30 4 Experimental section

4.1 General information

1H spectra were recorded on Bruker Avance 400 MHz spectrometer in deuterated chloroform as solvent, at 400.12 MHz respectively. Chemical shifts (δ) are quoted in parts per million (ppm) and the coupling constants (J) in Hertz (Hz). The following abbreviations are used to describe the multiplicity: s, singlet; d, doublet; t, triplet; q: quartet; quin.: quintet; dd, doublet of doublets; m, multiplet.

All reactants, 3-Fluorophenol(98%), 3-chlorophenol(98%), 3-bromophenol(98%), 3- iodophenol(98%), m-cresol(99%), 3-ethylphenol (99%), 3-tert-Butylphenol (99%), [1,1'- biphenyl]-3-ol (85%), 3-(trifluoromethyl)phenol (99%), 3-Acetamidophenol (97%), resorcinol (99%), 4-fluoro-3-methylphenol (98%), 4-chloro-3-methylphenol (98%), 3,4- dimethylphenol (98%), 4-isopropyl-3-methylphenol (99%), 3-methyl-4-(methylthio)phenol (97%). 4-hydroxy-2-methylbenzoic acid (98%), 3-chloro-4-fluorophenol (98%), 3,4- dichlorophenol (99%), 3-chloro-4-methylphenol (97%), 2-chloro-4-hydroxybenzonitrile 98% and allyl bromide were bought from Sigma Aldrich. Potassium carbonate (99.99%) and Potassium iodide (≥99.0%) was also bought from Sigma Aldrich. The organic solvent, acetone (≥99.8%) was bought from Honeywell. The organic solvents, hexane (95%) and ethyl acetate (99.8%) were bought from sigma Aldrich. The silica gel for the chromatography (40-63 μm, 0.060-0.300 m, F60) and preparative silica TLC plates (250 μm, F-255) were obtained from Silicycle. The nitrogen gas is from Isaga hf.

4.2 Synthetic protocols

4.2.1 General synthesis of allyl aryl ethers

The allyl aryl ethers were synthesized from substituted phenols using the SN2 reaction of phenoxide with allyl bromide. The job description goes like this. 0.5-3g of substituted phenol were dissolved in 75 mL of acetone in 100 mL round bottom flask. About 1.3 equivalent of K2CO3 (potassium carbonate) and 0.1 equivalent of KI (potassium iodide) were added to the solution as well as 1.5 equivalent of allyl bromide. This mixture was refluxed for 3 hours. After that the solution was filtered and the solvent evaporated off via rotary evaporator!

The product was purified by one of three methods. 1) via silica gel chromography where the mobile phase was 9:1 Hexane:Ethyl acetate. 2) by dissolving it in ethyl acetate and washing with a solution of KH2PO4, Na2CO3 and water. Then, it was dried over sodium sulfate, filtered and solvent evaporated off. 3) recrystallization from EtOAc (for m=NHCOCH3). In all purification methods the product was dried under high vacuum at the end.

31 4.2.2 General protocol for the Claisen rearrangement

For the Claisen rearrangement, 0.3-2g was put into 25-100mL Schlenk flask. The Schlenk flask is then connected to vacuum inert gas line and the reactant goes through three vacuum- nitrogen cycles before the reaction is set off by putting the Schlenk flask in an aluminum block and heated from room temperature up to 200°C. The temperature arose somewhat linearly but also a bit slowly.

In 4.3 the 1H NMR will be reported for the allyl phenyl ethers and the products of the Claisen rearrangement.

4.3 NMR analysis of products

4.3.1 1-(allyloxy)-3-fluorobenzene (1a)

1 H NMR (400 MHz, CDCl3) δ 7.27 – 7.17 (m, 1H), 6.74 – 6.60 (m, 3H), 6.05 (ddt, J = 17.3, 10.6, 5.3 Hz, 1H), 5.42 (dq, J = 17.3, 1.6 Hz, 1H), 5.31 (dq, J = 10.6, 1.4 Hz, 1H), 4.53 (dt, J = 5.3, 1.6 Hz, 2H).

Reference: BRS-i-15

Figure 4.1: 1H NMR of 1-(allyloxy)-3-fluorobenzene.

4.3.2 1-(allyloxy)-3-chlorobenzene (1b)

1 H NMR (400 MHz, CDCl3) δ 7.19 (t, J = 8.0 Hz, 1H), 6.97 – 6.87 (m, 2H), 6.81 (ddd, J = 8.4, 2.4, 1.0 Hz, 1H), 6.04 (ddt, J = 17.3, 10.5, 5.3 Hz, 1H), 5.41 (dq, J = 17.2, 1.6 Hz, 1H), 5.30 (dq, J = 10.5, 1.4 Hz, 1H), 4.52 (dt, J = 5.3, 1.6 Hz, 2H).

Reference: BRS-i-14

Figure 4.2: 1H NMR of 1-(allyloxy)-3-chlorobenzene.

4.3.3 1-(allyloxy)-3-bromobenzene (1c)

1 H NMR (400 MHz, CDCl3) δ 7.14 (t, J = 8.3 Hz, 1H), 7.10 – 7.05 (m, 2H), 6.85 (ddd, J = 8.2, 2.4, 1.3 Hz, 1H), 6.03 (ddt, J = 17.3, 10.5, 5.3 Hz, 1H), 5.41 (dq, J = 17.3, 1.6 Hz, 1H), 5.30 (dq, J = 10.5, 1.4 Hz, 1H), 4.52 (dt, J = 5.3, 1.5 Hz, 2H).

Reference: WTM-i-7

Figure 4.3: 1H NMR of 1-(allyloxy)-3-bromobenzene.

34 4.3.4 1-(allyloxy)-3-iodobenzene (1d)

1 H NMR (400 MHz, CDCl3) δ 7.31 – 7.26 (m, 2H), 6.99 (t, J = 8.0 Hz, 1H), 6.88 (ddd, J = 8.4, 2.4, 1.1 Hz, 1H), 6.03 (ddt, J = 17.2, 10.5, 5.2 Hz, 1H), 5.41 (dq, J = 17.2, 1.6 Hz, 1H), 5.30 (dq, J = 10.5, 1.5 Hz, 1H), 4.51 (dt, J = 5.3, 1.5 Hz, 2H).

Reference: BRS-i-5

Figure 4.4: 1H NMR of 1-(allyloxy)-3-iodobenzene.

35 4.3.5 1-(allyloxy)-3-methylbenzene (1e)

1 H NMR (400 MHz, CDCl3) δ 7.16 (t, J = 7.7 Hz, 1H), 6.82 – 6.69 (m, 3H), 6.06 (ddt, J = 17.2, 10.5, 5.3 Hz, 1H), 5.41 (dq, J = 17.3, 1.6 Hz, 1H), 5.28 (dq, J = 10.5, 1.4 Hz, 1H), 4.53 (dt, J = 5.3, 1.5 Hz, 2H), 2.33 (s, 3H).

Reference: BRS-i-11

Figure 4.5: 1H NMR of 1-(allyloxy)-3-methylbenzene.

36 4.3.6 1-(allyloxy)-3-ethylbenzene (1f)

1 H NMR (400 MHz, CDCl3) δ 7.19 (t, J = 7.8 Hz, 1H), 6.82 – 6.76 (m, 2H), 6.74 (ddd, J = 8.2, 2.6, 0.9 Hz, 1H), 6.07 (ddt, J = 17.3, 10.6, 5.3 Hz, 1H), 5.42 (dq, J = 17.3, 1.7 Hz, 1H), 5.28 (dq, J = 10.5, 1.4 Hz, 1H), 4.54 (dt, J = 5.3, 1.5 Hz, 2H), 2.63 (q, J = 7.6 Hz, 2H), 1.23 (t, J = 7.6 Hz, 3H).

Reference: BRS-i-12A

Figure 4.6: 1H NMR of 1-(allyloxy)-3-ethylbenzene.

37 4.3.7 1-(allyloxy)-3-(tert-butyl)benzene (1g)

1 H NMR (400 MHz, CDCl3) δ 7.22 (ddd, J = 8.2, 7.5, 0.7 Hz, 1H), 7.03 – 6.95 (m, 2H), 6.73 (ddd, J = 8.2, 2.5, 1.0 Hz, 1H), 6.15 – 6.01 (m, 1H), 5.43 (dq, J = 17.3, 1.6 Hz, 1H), 5.29 (dq, J = 10.5, 1.4 Hz, 1H), 4.55 (dt, J = 5.4, 1.5 Hz, 2H), 1.31 (d, J = 0.8 Hz, 9H).

Reference: WTM-i-50

Figure 4.7: 1H NMR of 1-(allyloxy)-3-(tert-butyl)benzene.

38 4.3.8 1-(allyloxy)-3-1,1’biphenyl (1h)

1 H NMR (400 MHz, CDCl3) δ 7.64 – 7.55 (m, 2H), 7.49 – 7.39 (m, 2H), 7.39 – 7.32 (m, 2H), 7.19 (ddd, J = 7.6, 1.7, 1.0 Hz, 1H), 7.16 (dd, J = 2.6, 1.7 Hz, 1H), 6.92 (ddd, J = 8.2, 2.6, 1.0 Hz, 1H), 6.10 (ddt, J = 17.3, 10.6, 5.3 Hz, 1H), 5.45 (dq, J = 17.3, 1.6 Hz, 1H), 5.32 (dq, J = 10.5, 1.4 Hz, 1H), 4.61 (dt, J = 5.3, 1.5 Hz, 2H).

Reference: BRS-i-9A

Figure 4.8: 1H NMR of 1-(allyloxy)-3-1,1’biphenyl.

39 4.3.9 1-(allyloxy)-3-(trifluoromethyl)benzene (1i)

1 H NMR (400 MHz, CDCl3) δ 7.38 (tdd, J = 8.3, 1.3, 0.7 Hz, 1H), 7.21 (ddt, J = 7.7, 1.6, 0.8 Hz, 1H), 7.15 (t, J = 2.1 Hz, 1H), 7.11 – 7.06 (m, 1H), 6.05 (ddt, J = 17.3, 10.6, 5.3 Hz, 1H), 5.43 (dq, J = 17.2, 1.6 Hz, 1H), 5.32 (dq, J = 10.5, 1.4 Hz, 1H), 4.58 (dt, J = 5.2, 1.5 Hz, 2H).

Reference: WTM-i-12

Figure 4.9: 1H NMR of 1-(allyloxy)-3-(trifluoromethyl)benzene.

40 4.3.10 N-(3-(allyloxy)phenyl)acetamide (1j)

1 H NMR (400 MHz, CDCl3) δ 7.69 (s, 1H), 7.29 (d, J = 2.3 Hz, 1H), 7.17 (t, J = 8.1 Hz, 1H), 6.97 (dd, J = 8.0, 2.0 Hz, 1H), 6.66 (dd, J = 8.4, 2.5 Hz, 1H), 6.02 (ddt, J = 17.5, 10.5, 5.3 Hz, 1H), 5.39 (dt, J = 17.2, 1.8 Hz, 1H), 5.26 (dd, J = 10.5, 1.6 Hz, 1H), 4.50 (dt, J = 5.4, 1.7 Hz, 2H), 2.15 (s, 3H).

Reference: BRS-i-8

Figure 4.10: 1H NMR of N-(3-(allyloxy)phenyl)acetamide.

41 4.3.11 1,3-bis(allyloxy)benzene (1k)

1 H NMR (400 MHz, CDCl3) δ 7.17 (t, J = 8.3 Hz, 1H), 6.56 – 6.49 (m, 3H), 6.05 (dddt, J = 17.9, 10.3, 7.3, 5.2 Hz, 2H), 5.42 (dq, J = 17.2, 1.7 Hz, 2H), 5.29 (dt, J = 10.4, 1.5 Hz, 2H), 4.52 (dq, J = 5.9, 2.6, 2.1 Hz, 4H).

Reference: WTM-i-49A

Figure 4.11: 1H NMR of 1,3-bis(allyloxy)benzene.

42 4.3.12 4-(allyloxy)-1-fluoro-2-methylbenzene (2a)

1 H NMR (400 MHz, CDCl3) δ 6.90 (t, J = 9.0 Hz, 1H), 6.73 (dd, J = 6.3, 3.2 Hz, 1H), 6.67 (dt, J = 9.1, 3.5 Hz, 1H), 6.04 (ddt, J = 17.2, 10.5, 5.3 Hz, 1H), 5.40 (dq, J = 17.3, 1.6 Hz, 1H), 5.28 (dq, J = 10.5, 1.4 Hz, 1H), 4.48 (dt, J = 5.3, 1.5 Hz, 2H), 2.25 (d, J = 2.1 Hz, 3H).

Reference: SDH-i-62

Figure 4.12: 1H NMR of 4-(allyloxy)-1-fluoro-2-methylbenzene.

43 4.3.13 4-(allyloxy)-1-chloro-2-methylbenzene (2b)

1 H NMR (400 MHz, CDCl3) δ 7.21 (d, J = 8.7 Hz, 1H), 6.79 (d, J = 3.0 Hz, 1H), 6.69 (dd, J = 8.7, 3.5 Hz, 1H), 6.03 (ddt, J = 17.2, 10.5, 5.2 Hz, 1H), 5.40 (dq, J = 17.3, 1.6 Hz, 1H), 5.28 (dq, J = 10.5, 1.4 Hz, 1H), 4.50 (dt, J = 5.2, 1.5 Hz, 2H), 2.34 (s, 3H).

Reference: SDH-i-44

Figure 4.13: 1H NMR of 4-(allyloxy)-1-chloro-2-methylbenzene.

44 4.3.14 4-(allyloxy)-1,2-dimethylbenzene (2c)

1 H NMR (400 MHz, CDCl3) δ 7.03 (d, J = 8.3 Hz, 1H), 6.74 (d, J = 2.7 Hz, 1H), 6.66 (dd, J = 8.3, 2.7 Hz, 1H), 6.06 (ddtd, J = 17.3, 10.6, 5.3, 1.6 Hz, 1H), 5.41 (dp, J = 17.2, 1.7 Hz, 1H), 5.27 (dt, J = 10.6, 1.5 Hz, 1H), 4.51 (dt, J = 5.3, 1.5 Hz, 2H), 2.24 (s, 3H), 2.20 (s, 3H).

Reference: SDH-i-56

Figure 4.14: 1H NMR of 4-(allyloxy)-1,2-dimethylbenzene.

45 4.3.15 4(allyloxy)-1-isopropyl-2-methylbenzene (2d)

1 H NMR (400 MHz, CDCl3) δ 7.14 (d, J = 8.3 Hz, 1H), 6.74 (dd, J = 8.3, 2.8 Hz, 1H), 6.71 (d, J = 2.8 Hz, 1H), 6.06 (ddt, J = 17.3, 10.6, 5.3 Hz, 1H), 5.40 (dq, J = 17.3, 1.6 Hz, 1H), 5.27 (dq, J = 10.5, 1.5 Hz, 1H), 4.51 (dt, J = 5.3, 1.5 Hz, 2H), 3.07 (hept, J = 6.8 Hz, 1H), 2.31 (s, 3H), 1.20 (d, J = 6.8 Hz, 6H).

Reference: SDH-i-46

Figure 4.15: 1H NMR of 4-(allyloxy)-1-isopropyl-2-methylbenzene.

46 4.3.16 (4-(allyloxy)-2-methylphenyl)(methyl)sulfane (2e)

1 H NMR (400 MHz, CDCl3) δ 7.19 (d, J = 8.5 Hz, 1H), 6.78 (d, J = 2.9 Hz, 1H), 6.75 (dd, J = 8.4, 2.8 Hz, 1H), 6.05 (ddt, J = 17.3, 10.6, 5.3 Hz, 1H), 5.40 (dq, J = 17.3, 1.6 Hz, 1H), 5.28 (dq, J = 10.6, 1.5 Hz, 1H), 4.54 – 4.48 (m, 2H), 2.39 (s, 3H), 2.37 (s, 3H).

SDH-i-50

Figure 4.16: 1H NMR of (4-(allyloxy)-2-methylphenyl)(methyl)sulfane.

47 4.3.17 4-(allyloxy)-2-chloro-1-fluorobenzene (2f)

1 H NMR (400 MHz, CDCl3) δ 7.04 (t, J = 8.8 Hz, 1H), 6.94 (dd, J = 5.9, 3.0 Hz, 1H), 6.77 (ddd, J = 9.1, 3.8, 3.0 Hz, 1H), 6.02 (ddt, J = 17.2, 10.5, 5.2 Hz, 1H), 5.40 (dq, J = 17.3, 1.6 Hz, 1H), 5.30 (dq, J = 10.6, 1.4 Hz, 1H), 4.49 (dt, J = 5.2, 1.5 Hz, 2H).

Reference: WTM-i-16

Figure 4.17: 1H NMR of 4-(allyloxy)-2-chloro-1-fluorobenzene.

48 4.3.18 4-(allyloxy)-1,2-dichlorobenzene (3a)

1 H NMR (400 MHz, CDCl3) δ 7.31 (d, J = 9.0 Hz, 1H), 7.01 (d, J = 2.9 Hz, 1H), 6.77 (dd, J = 8.8, 2.9 Hz, 1H), 6.01 (ddt, J = 17.3, 10.6, 5.3 Hz, 1H), 5.40 (dq, J = 17.2, 1.6 Hz, 1H), 5.31 (dq, J = 10.6, 1.4 Hz, 1H), 4.50 (dt, J = 5.3, 1.6 Hz, 2H).

Reference: SDH-i-48

Figure 4.18: 1H NMR of 4-(allyloxy)-1,2-dichlorobenzene.

49 4.3.19 4-(allyloxy)-2-chloro-1-methylbenzene (3b)

1 H NMR (400 MHz, CDCl3) δ 7.10 (d, J = 7.6 Hz, 1H), 6.93 (d, J = 2.7 Hz, 1H), 6.73 (dd, J = 8.5, 2.7 Hz, 1H), 6.03 (ddt, J = 17.3, 10.6, 5.3 Hz, 1H), 5.40 (dq, J = 17.2, 1.6 Hz, 1H), 5.29 (dq, J = 10.5, 1.5 Hz, 1H), 4.50 (dt, J = 5.3, 1.6 Hz, 2H), 2.29 (s, 3H).

Reference: SDH-i-58

Figure 4.19: 1H NMR of 4-(allyloxy)-2-chloro-1-methylbenzene.

50 4.3.20 4-(allyloxy)-2-chlorobenzonitrile (3d)

1 H NMR (400 MHz, CDCl3) δ 7.49 (d, J = 8.7 Hz, 1H), 6.95 (d, J = 2.4 Hz, 1H), 6.81 (dd, J = 8.7, 2.4 Hz, 1H), 5.94 (ddt, J = 17.2, 10.5, 5.3 Hz, 1H), 5.35 (dq, J = 17.3, 1.5 Hz, 1H), 5.28 (dq, J = 10.5, 1.4 Hz, 1H), 4.52 (dt, J = 5.3, 1.6 Hz, 2H).

Reference: BRS-i-28

Figure 4.20: 1H NMR of 4-(allyloxy)-2-chlorobenzonitrile.

51 4.3.21 Products from Claisen rearrangement of 1-(allyloxy)-3- fluorobenzene (1a)

Reference: WTM-i-60C

Figure 4.21: 1H NMR of isomer A and B from Claisen rearrangement of 1-(allyloxy)-3- fluorobenzene.

52 4.3.22 Products from Claisen rearrangement of 1-(allyloxy)-3- chlorobenzene (1b)

Isomer A

1 H NMR (400 MHz, CDCl3) δ 7.03 (d, J = 8.2 Hz, 1H), 6.87 (dd, J = 8.1, 2.1 Hz, 1H), 6.84 (d, J = 2.1 Hz, 1H), 6.06 – 5.90 (m, 1H), 5.22 – 5.02 (m, 2H), 3.37 (dt, J = 6.3, 1.7 Hz, 2H).

Isomer B

1 H NMR (400 MHz, CDCl3) δ 7.05 (t, J = 8.0 Hz, 1H), 6.99 (dd, J = 8.1, 1.4 Hz, 1H), 6.73 (dd, J = 7.9, 1.4 Hz, 1H), 6.06 – 5.90 (m, 1H), 5.22 – 5.02 (m, 2H), 3.60 (dt, J = 6.0, 1.7 Hz, 2H).

Reference: WTM-i-58

Figure 4.22: 1H NMR of isomer A and B from Claisen rearrangement of 1-(allyloxy)-3- chlorobenzene.

53 4.3.23 Products from Claisen rearrangement of 1-(allyloxy)-3- bromobenzene (1c)

Isomer B:

1 H NMR (400 MHz, CDCl3) δ 7.17 (dd, J = 8.1, 1.2 Hz, 1H), 6.98 (t, J = 8.0 Hz, 1H), 6.77 (dd, J = 8.1, 1.2 Hz, 1H), 6.10 – 5.90 (m, 1H), 5.20 – 5.09 (m, 2H), 5.07 (br s, 1H) 3.63 (dt, J = 6.0, 1.7 Hz, 2H).

Isomer A:

1 H NMR (400 MHz, CDCl3) δ 7.02 (dd, J = 8.0, 1.9 Hz, 1H), 6.99 (d, J = 1.9 Hz, 1H), 6.97 (d, J = 8.0 Hz, 2H), 6.10 – 5.90 (m, 3H), 5.21 – 5.09 (m, 5H), 5.07 (br s, 1H) 3.36 (dt, J = 6.3, 1.7 Hz, 2H).

Reference: WTM-i-57B

Figure 4.23: 1H NMR of isomer A and B from Claisen rearrangement of 1-(allyloxy)-3- bromobenzene.

54 4.3.24 Products from Claisen rearrangement of 1-(allyloxy)-3- iodobenzene (1d)

Reference: WTM-i-67B

Figure 4.24: 1H NMR of isomer A and B from Claisen rearrangement of 1-(allyloxy)-3- iodobenzene.

55 4.3.25 Products from Claisen rearrangement of 1-(allyloxy)-3- methylbenzene (1e)

The compounds are unseparable according to several references but looking at the integration and peak splitting patterns this is likely the separate NMR patterns – although the coupling constants do not match as well as one would expect.

Isomer A

1 H NMR (400 MHz, CDCl3) δ 6.91 (d, J = 8.2 Hz, 1H), 6.63 (ddd, J = 7.6, 1.7, 0.8 Hz, 1H), 6.57 (d, J = 1.6 Hz, 1H), 6.01 – 5.82 (m, 1H), 5.12 – 5.05 (m, 2H), 3.30 (dd, J = 6.3, 1.7 Hz, 2H), 2.21 (s, 3H).

Isomer B

1 H NMR (400 MHz, CDCl3) δ 6.94 (t, J = 7.7 Hz, 1H), 6.70 (d, J = 7.6 Hz, 2H), 6.60 (d, J = 8.0 Hz, 1H), 6.01 – 5.82 (m, 1H), 5.02 – 4.92 (m, 2H), 3.36 (dt, J = 5.8, 1.8 Hz, 2H), 2.22 (s, 3H).

Reference: WTM-i-42B

Figure 4.25: 1H NMR of isomer A and B from Claisen rearrangement of 1-(allyloxy)-3- methylbenzene.

56 4.3.26 Products from Claisen rearrangement of 1-(allyloxy)-3- ethylbenzene (1f)

Reference: WTM-i-44B

Figure 4.26: 1H NMR of isomer A and B from Claisen rearrangement of 1-(allyloxy)-3- ethylbenzene.

57 4.3.27 Products from Claisen rearrangement of 1-(allyloxy)-3- (tert-butyl)benzene (1g)

Reference: WTM-i-61

Figure 4.27: 1H NMR of isomer A and B from Claisen rearrangement of 1-(allyloxy)-3-(tert- butyl)benzene.

58 4.3.28 Products from Claisen rearrangement of 3-(allyloxy)- 1,1'-biphenyl (1h)

Reference: WTM-i-62C

Figure 4.28: 1H NMR of isomer A and B from Claisen rearrangement of 3-(allyloxy)-1,1’- biphenyl.

59 4.3.29 Products from Claisen rearrangement of 1-(allyloxy)-3- (trifluoromethyl)benzene (1i)

Refrence: WTM-i-46C

Figure 4.29: 1H NMR of isomer A and B from Claisen rearrangement of 1-(allyloxy)-3- (trifluoromethyl)benzene.

60 4.3.30 Products from Claisen rearrangement of N-(3- (allyloxy)phenyl)acetamide (1j)

Reference: WTM-i-46C

Figure 4.30: 1H NMR of isomer A and B from Claisen rearrangement of N-(3- (allyloxy)phenyl)acetamide.

61 4.3.31 Products from Claisen rearrangement of 1,3- bis(allyloxy)benzene (1k)

Reference: WTM-i-49B

Figure 4.31: 1H NMR of isomer A and B from Claisen rearrangement of 1,3- bis(allyloxy)benzene.

62 4.3.32 Products from Claisen rearrangement of 4-(allyloxy)-1- fluoro-2-methylbenzene (2a)

Reference: WTM-i-66

Figure 4.32: 1H NMR of isomer A and B from Claisen rearrangement of 4-(allyloxy)-1- fluoro-2-methylbenzene.

63 4.3.33 Products from Claisen rearrangement of 4-(allyloxy)-1- chloro-2-methylbenzene (2b) wtm-i-55b

Isomer A

1 H NMR (400 MHz, CDCl3) δ 7.09 (s, 1H), 6.71 (d, J = 0.8 Hz, 1H), 6.07 – 5.89 (m, 1H), 5.20 (t, J = 1.6 Hz, 1H), 5.17 (dq, J = 8.0, 1.6 Hz, 1H), 4.88 (s, 1H), 3.36 (dt, J = 6.3, 1.7 Hz, 2H), 2.32 (s, 3H).

Isomer B

1 H NMR (400 MHz, CDCl3) δ 7.15 (d, J = 8.6 Hz, 1H), 6.65 (d, J = 8.6 Hz, 1H), 6.07 – 5.89 (m, 1H), 5.10 (dq, J = 10.1, 1.6 Hz, 1H), 5.01 (dq, J = 17.2, 1.8 Hz, 1H), 4.81 (s, 1H), 3.48 (dt, J = 5.7, 1.8 Hz, 2H), 2.36 (s, 3H).

A:B ratio 1:1.64

Reference: WTM-i-55b

Figure 4.33: 1H NMR of isomer A and B from Claisen rearrangement of 4-(allyloxy)-1- chloro-2-methylbenzene.

4.3.34 Products from Claisen rearrangement of 4-(allyloxy)- 1,2-dimethylbenzene (2c)

Isomer A

1 H NMR (400 MHz, CDCl3) δ 6.88 (s, 1H), 6.65 (s, 1H), 6.10 – 5.94 (m, 1H), 5.24 – 5.12 (m, 2H), 3.38 (dt, J = 6.4, 1.7 Hz, 2H), 2.xy (s, 3H), 2.20 (s, 3H).

Isomer B

1 H NMR (400 MHz, CDCl3) δ 6.94 (d, J = 8.2 Hz, 1H), 6.61 (d, J = 8.1 Hz, 1H), 6.08 – 5.97 (m, 1H), 5.08 (dq, J = 10.1, 1.7 Hz, 1H), 5.02 (dq, J = 17.1, 1.9 Hz, 1H), 3.49 (dt, J = 5.8, 1.8 Hz, 2H), 2.25 (s, 3H), 2.21 (s, 3H).

A:B ratio 1:1.18

Reference: BRS-i-25A

Figure 4.34: 1H NMR of isomer A and B from Claisen rearrangement of 4-(allyloxy)-1,2- dimethylbenzene.

65 4.3.35 Products from Claisen rearrangement of 4-(allyloxy)-1- isopropyl-2-methylbenzene (2d)

Isomer A

1 H NMR (400 MHz, CDCl3) δ 6.87 (s, 1H), 6.53 (s, 1H), 6.03 – 5.83 (m, 1H), 5.09 (dq, J = 25.0, 1.7 Hz, 1H), 5.08 (p, J = 1.6 Hz, 1H), 3.31 (dt, J = 6.4, 1.8 Hz, 2H), 2.96 (hept, J = 6.8 Hz, 1H), 2.19 (s, 3H), 1.12 (d, J = 6.9 Hz, 6H).

Isomer B

1 H NMR (400 MHz, CDCl3) δ 6.95 (d, J = 8.3 Hz, 1H), 6.59 (d, J = 8.3 Hz, 1H), 6.03 – 5.83 (m, 1H), 4.96 (dq, J = 6.3, 1.8 Hz, 1H), 4.95 (dq, J = 33.5, 1.8 Hz, 1H), 3.40 (dt, J = 5.8, 1.8 Hz, 2H), 3.06 (hept, J = 6.8 Hz, 1H), 2.18 (s, 3H), 1.12 (d, J = 6.8 Hz, 6H).

A:B ratio 1:1.29

Reference: WTM-i-59E

Figure 4.35: 1H NMR of isomer A and B from Claisen rearrangement of 4-(allyloxy)-1- isopropyl-2-methylbenzene.

66 4.3.36 Products from Claisen rearrangement of (4-(allyloxy)-2- methylphenyl)(methyl)sulfane (2e)

Isomer A

1 H NMR (400 MHz, CDCl3) δ 7.06 (s, 1H), 6.70 (s, 1H), 6.13 – 5.90 (m, 1H), 5.20 (dq, J = 6.4, 1.7 Hz, 1H), 5.17 (t, J = 1.6 Hz, 1H), 3.40 (dt, J = 6.3, 1.7 Hz, 2H), 2.41 (s, 3H), 2.36 (s, 3H).

Isomer B

1 H NMR (400 MHz, CDCl3) δ 7.14 (d, J = 8.4 Hz, 1H), 6.70 (d, J = 8.7 Hz, 1H), 6.13 – 5.90 (m, 1H), 5.09 (dq, J = 10.1, 1.7 Hz, 1H), 5.02 (dq, J = 17.2, 1.8 Hz, 1H), 3.49 (dt, J = 5.8, 1.8 Hz, 2H), 2.41 (s, 3H), 2.40 (s, 3H).

A:B ratio 1.14

Reference: WTM-i-65

Figure 4.36: 1H NMR of isomer A and B from Claisen rearrangement of (4-(allyloxy)-2- methylphenyl)(methyl)sulfane.

67 4.3.37 Products from Claisen rearrangement of 4-(allyloxy)-2- chloro-1-fluorobenzene (3a)

Isomer A

1 H NMR (400 MHz, CDCl3) δ 6.93 (d, J = 9.3 Hz, 1H), 6.88 (d, J = 6.2 Hz, 1H), 6.05 – 5.90 (m, 1H), 5.27 – 5.09 (m, 2H), 3.37 (dt, J = 6.3, 1.7 Hz, 2H)

Isomer B

1 H NMR (400 MHz, CDCl3) δ 6.96 (t, J = 8.7 Hz, 1H), 6.72 (dd, J = 8.8, 4.3 Hz, 1H), 6.05 – 5.90 (m, 1H), 5.27 – 5.09 (m, 2H), 3.62 (dt, J = 6.1, 1.8 Hz, 2H).

A:B ratio 1:1.55

Reference: WTM-i-45

Figure 4.37: 1H NMR of isomer A and B from Claisen rearrangement of 4-(allyloxy)-2- chloro-1-fluorobenzene.

68 4.3.38 Products from Claisen rearrangement of 4-(allyloxy)- 1,2-dichlorobenzene (3b)

Reference: WTM-i-70

Figure 4.38: 1H NMR of isomer A and B from Claisen rearrangement of 4-(allyloxy)-2- chloro-1-chlorobenzene.

69 4.3.39 Products from Claisen rearrangement of 4-(allyloxy)-2- chloro-1-methylbenzene (3c)

Isomer A

1 H NMR (400 MHz, CDCl3) δ 6.94 (d, J = 0.8 Hz, 1H), 6.84 (s, 1H), 6.10 – 5.89 (m, 1H), 5.09 (dp, J = 7.2, 1.8 Hz, 2H), 3.34 (dt, J = 6.3, 1.7 Hz, 2H), 2.27 (d, J = 0.7 Hz, 3H).

Isomer B

1 H NMR (400 MHz, CDCl3) δ 6.99 (dd, J = 8.2, 0.8 Hz, 1H), 6.66 (d, J = 8.2 Hz, 1H), 6.04 – 5.91 (m, 1H), 5.18 – 5.11 (m, 2H), 3.62 (dt, J = 6.0, 1.7 Hz, 2H), 2.31 (d, J = 0.7 Hz, 3H).

Reference: BRS-i-58

Figure 4.39: 1H NMR of isomer A and B from Claisen rearrangement of 4-(allyloxy)-2- chloro-1-methylbenzene.

4.3.40 Products from Claisen rearrangement of 4-(allyloxy)-2- chlorobenzonitrile (3d)

Isomer A

1 H NMR (400 MHz, CDCl3) δ 7.41 (s, 1H), 6.98 (s, 1H), 6.21 (s, 1H), 6.08 – 5.85 (m, 1H), 5.25 – 5.15 (m, 2H), 3.38 (dd, J = 6.5, 1.7 Hz, 2H).

Isomer B

1 H NMR (400 MHz, CDCl3) δ 7.45 (d, J = 8.5 Hz, 1H), 6.84 (d, J = 8.5 Hz, 1H), 6.17 (s, 1H), 6.08 – 5.85 (m, 1H), 5.17 – 5.08 (m, 2H), 3.61 (dt, J = 6.1, 1.7 Hz, 2H).

Reference: BRS-i-64

Figure 4.40: 1H NMR of isomer A and B from Claisen rearrangement of 4-(allyloxy)-2- chlorobenzonitrile.

71 5 Computational calculations

5.1 General information

A series of geometry optimizations of reactants, transition states and products for Claisen rearrangement were performed on Garpur and Jötunn clusters. Garpur I is Lenovo 36 nodes and Garpur II is Lenovo 8 FAT nodes both NextScale models. Jötunn is IBM, HS20 model and has 42 nodes. To access the servers the program MobaXterm was used. For the calculations and optimizations, the ORCA 4.2.0 package was used.39 The optimizations were done at B3LYP/def2-TZVP level of theory and then a few handpicked Claisen rearrangement reactants, transition states and products were done at another level of theory, DLPNO-CCSD(T)/def2-TZVP to confirm similar trend in results for energies.

The simple-input line in the optimizations was like this:

!UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRIDX4 tightopt freq

UKS means unrestricted electronic formalism or there are two spatial orbitals for two unpaired electrons. This is important when reaction mechanisms are investigated because the transition state geometry can have bi-radical character.

B3LYP is level of theory used for investigation. B3LYP is Becke 88 exchange functional with Lee-Yang-Parr correlation functional. 3 in B3LYP stands for that there are 3 parameters in the functional that are then fit towards very high benchmark sets of chemical features. This functional use 20% of exact exchange from HF and is therefore hybrid functional.

RIJCOSX is approximation on Coloumb and exchange integration in the calculations and it can speed up the calculations without losing accuracy. For this approximation an auxiliary basis set needs to be defined -> def2/J.

GRID4 is the size of the numerical grid which is used to calculate the energy with DFT. Default is 2 which can be a little low for many applications. GRIDX is the size on the grid in COSX approximation. The bigger the grid the more points are to calculate and that means bigger numerical calculation and it takes longer time. Finally, tightopt is keyword to get “tight geometric convergence”.

For the output there are three important instructions put in the orca input file. First the orca is asked to print out the Hirshfeld charges by the command Print[ P_Hirshfeld], secondly for other necessary information like basis sets and MO coefficients so that Chemcraft can later render the orbitals for visualization the commands Print[ P_MOs] and Print[ P_Basis] were used.

To find the transition states the NEB-TS was used.40 The Nudged Elastic Band (NEB) can be used to find the minimum energy path and also the saddle point between two minima. The main advantage of the method is that only gradients are required. The method converges to the minimum path (MEP) and allows convenient saddle-point optimization in the same job.

72 The orca output files were visualized and data from them analyzed with the program chemcraft version 1.8 programmed by G. A. Andrienko.41 The pictures of geometries were created with the open source molecular viewer licensed under the GNU Lesser General Public License, Jmol 14.30.2(2019-11-26 10:18).42 In order to view geometries in Jmol the orca output files had to be converted to molden.input file. This was done by using program, part of the orca package called orca_2mkl. The unix command was orca_2mkl nameoftheorcaoutputfile – molden.

ORCA output file gives Mulliken, Löwden and Hirshfeld population analysis. To confirm the values from ORCA and add Natural population analysis a program called JANPA 2.01 was used. JANPA is a freeware program package initially aimed at performing natural population analysis, a method for partial atomic charges calculation and natural atomic orbital creation.43,44

Finally, for molecular orbital analysis the open source program Multiwfn - A multifunctional wavefunction analyzer, version 3.7, release date 23.04.2020 was used. Project leader of Multiwfn is Tian Lu(Beijing Kein research center for natural science).45

In 5.2 the orca input files for reactants, transition states and products are given.

5.2 Orca input files

5.2.1 Claisen rearrangement of 1-(allyloxy)-3-fluorobenzene (1a)

Reactant ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP FREQ

%output Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1 6 1.057995000 2.012090000 -1.659005000

6 -0.168088000 1.723724000 -1.084811000

6 2.198065000 1.280664000 -1.330451000

1 -1.054746000 2.289588000 -1.334968000

1 3.163059000 1.488625000 -1.769592000

6 -0.276461000 0.684837000 -0.156084000

6 2.055707000 0.259735000 -0.413153000

73 6 0.849157000 -0.062991000 0.186840000

1 0.814995000 -0.888521000 0.878148000

1 1.132691000 2.819800000 -2.375495000

8 -1.516403000 0.488633000 0.369432000

9 3.139378000 -0.476882000 -0.077177000

6 -1.730277000 -0.577895000 1.295153000

6 -1.759933000 -1.924259000 0.637588000

6 -1.159468000 -3.003471000 1.118183000

1 -0.991282000 -0.545155000 2.101685000

1 -2.706982000 -0.352156000 1.727635000

1 -2.345131000 -1.980629000 -0.275388000

1 -0.561594000 -2.966070000 2.022701000

1 -1.243018000 -3.965826000 0.630321000 *

Transition state A ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP NEB-TS PAL8

%neb nimages = 8 NEB_END_XYZfile = “product.xyz” NEB_TS_XYZfile = “guess1” end

%output Print[ P_Basis ] 3 Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1 6 1.349673000 0.995470000 -1.133185000

6 0.161026000 1.137119000 -0.376949000

6 2.394106000 0.248514000 -0.660180000

1 -0.561588000 1.891419000 -0.651254000

74 1 3.307081000 0.106395000 -1.220913000

6 0.084206000 0.630703000 0.970151000

6 2.266980000 -0.339462000 0.615947000

6 1.172059000 -0.192935000 1.411453000

1 1.124822000 -0.651803000 2.389027000

1 1.421658000 1.469379000 -2.104103000

8 -0.951890000 0.803170000 1.673876000

9 3.306730000 -1.083498000 1.050687000

6 -2.565712000 -0.429063000 0.738182000

6 -1.764682000 -1.102058000 -0.144638000

6 -1.227609000 -0.460421000 -1.255684000

1 -2.889350000 -0.879818000 1.664206000

1 -3.027823000 0.508164000 0.466553000

1 -1.327989000 -2.044966000 0.164896000

1 -1.765257000 0.356774000 -1.714108000

1 -0.506441000 -0.963080000 -1.883967000 *

Transition state B ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP NEB-TS PAL8

%neb nimages = 8 NEB_END_XYZfile = “product.xyz” NEB_TS_XYZfile = “guess1” end

%output Print[ P_Basis ] 3 Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1 6 0.562210000 4.960555000 2.346644000

75 6 -0.685883000 4.543480000 1.818869000

6 1.613530000 4.096832000 2.486481000

1 -1.509038000 5.233515000 1.700051000

1 2.567354000 4.426244000 2.876793000

6 -0.818007000 3.240055000 1.449244000

6 1.506646000 2.731257000 2.061761000

6 0.207101000 2.286213000 1.622731000

1 0.127138000 1.335141000 1.118482000

1 0.676046000 5.997255000 2.638444000

8 2.460764000 1.903227000 2.182721000

9 -1.989343000 2.796879000 0.938440000

6 2.026041000 0.877120000 4.014655000

6 0.748852000 0.470765000 3.713010000

6 -0.282282000 1.395329000 3.600601000

1 -1.276107000 1.077929000 3.316081000

1 -0.223351000 2.342729000 4.119782000

1 0.602705000 -0.521081000 3.300411000

1 2.856585000 0.187420000 3.983211000

1 2.204355000 1.818523000 4.513020000 *

Product A ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP FREQ

%output Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1 6 -1.925565000 0.363011000 -3.425679000

6 -2.781610000 -0.359815000 -2.434511000

76 6 -0.948585000 1.199098000 -3.061069000

1 -3.710340000 0.233957000 -2.385186000

1 -0.352293000 1.749801000 -3.775713000

6 -2.260318000 -0.319192000 -0.991505000

6 -0.668369000 1.379080000 -1.656931000

6 -1.277425000 0.710254000 -0.664900000

1 -0.983612000 0.834480000 0.367851000

1 -2.154645000 0.218822000 -4.474821000

8 -2.667880000 -1.106120000 -0.158095000

9 0.297784000 2.269043000 -1.378706000

6 -5.447933000 -1.655906000 -1.780235000

6 -4.566300000 -2.236199000 -2.580872000

6 -3.170276000 -1.778827000 -2.891681000

1 -6.432734000 -2.080700000 -1.635932000

1 -5.222081000 -0.761350000 -1.213683000

1 -4.849892000 -3.156284000 -3.085305000

1 -2.463736000 -2.493216000 -2.456594000

1 -3.028837000 -1.846257000 -3.974772000 *

Product B ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP FREQ

%output Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1 6 1.209589000 -0.873674000 -2.048463000

6 -0.120123000 -0.956038000 -1.843870000

6 2.052613000 0.099913000 -1.384388000

77 1 -0.741450000 -1.660362000 -2.380110000

1 3.105069000 0.170539000 -1.619784000

6 -0.799439000 -0.011783000 -0.958639000

6 1.500480000 0.908275000 -0.478946000

6 0.082641000 0.845071000 -0.044962000

1 -0.341343000 1.852634000 -0.023113000

1 1.685186000 -1.543511000 -2.754936000

8 -2.009869000 0.096371000 -0.907912000

9 2.240414000 1.830043000 0.165931000

6 -1.935448000 -0.744535000 2.565063000

6 -1.335439000 0.304725000 2.021039000

6 0.028849000 0.273044000 1.412597000

1 -2.914340000 -0.664821000 3.019347000

1 -1.470782000 -1.724316000 2.570322000

1 -1.839519000 1.266506000 2.015171000

1 0.712315000 0.883489000 2.009453000

1 0.422080000 -0.746015000 1.409481000 *

5.2.2 Claisen rearrangement of 1-(allyloxy)-3-chlorobenzene (1b)

Reactant ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP FREQ

%output Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1 6 -0.750699000 -0.909275000 3.611907000

6 -2.112383000 -0.854150000 3.328948000

78 6 -0.285714000 -1.070755000 4.907371000

1 -2.434982000 -0.734011000 2.306084000

1 0.770764000 -1.115854000 5.126796000

6 -3.032502000 -0.960018000 4.371674000

6 -1.221859000 -1.176898000 5.930968000

6 -2.580508000 -1.124022000 5.684177000

1 -3.300633000 -1.205879000 6.485222000

1 -0.040327000 -0.826379000 2.799346000

8 -4.382950000 -0.908237000 4.229133000

17 -0.668068000 -1.383576000 7.574339000

6 -4.953953000 -0.802056000 2.919787000

6 -4.976565000 -2.117076000 2.205417000

6 -6.077800000 -2.661522000 1.705211000

1 -6.055182000 -3.610091000 1.184023000

1 -7.043753000 -2.175817000 1.790481000

1 -4.025105000 -2.629722000 2.107915000

1 -4.417025000 -0.038672000 2.346515000

1 -5.968345000 -0.442991000 3.087851000 *

Transition state A ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP NEB-TS PAL8

%neb nimages = 8 NEB_END_XYZfile = “product.xyz” NEB_TS_XYZfile = “guess1” end

%output Print[ P_Basis ] 3 Print[ P_Basis ] 2

79 Print[ P_MOs ] 1 end

*xyz 0 1

6 -1.537187000 1.241093000 -0.524396000

6 -0.280555000 0.684744000 -0.878282000

6 -2.427270000 0.536920000 0.236635000

1 0.321131000 1.162826000 -1.637170000

1 -3.376377000 0.958918000 0.533678000

6 0.000479000 -0.698297000 -0.591342000

6 -2.100345000 -0.786763000 0.622141000

6 -0.935898000 -1.391559000 0.247829000

1 -0.711789000 -2.409726000 0.533174000

1 -1.779392000 2.248316000 -0.839861000

8 1.091818000 -1.234224000 -0.951391000

17 -3.257710000 -1.656870000 1.600880000

6 2.514466000 -0.512751000 0.499089000

6 2.269980000 0.828972000 0.342750000

6 1.064167000 1.387696000 0.752159000

1 0.481623000 0.917277000 1.533067000

1 0.868470000 2.438882000 0.594834000

1 2.898907000 1.395038000 -0.335264000

1 1.973649000 -1.094392000 1.231211000

1 3.392048000 -0.976589000 0.073526000 *

Transition state B ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP NEB-TS PAL8

%neb nimages = 8

80 NEB_END_XYZfile = “product.xyz” NEB_TS_XYZfile = “guess1” end

%output Print[ P_Basis ] 3 Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1

6 0.588074000 4.964998000 2.366466000

6 -0.657968000 4.551451000 1.833114000

6 1.637330000 4.099407000 2.503265000

1 -1.470915000 5.254545000 1.723887000

1 2.590920000 4.423641000 2.899043000

6 -0.807375000 3.249377000 1.449155000

6 1.527118000 2.736860000 2.070330000

6 0.227636000 2.298146000 1.623865000

1 0.159388000 1.343749000 1.125420000

1 0.700547000 6.000378000 2.664143000

8 2.478053000 1.906436000 2.188833000

17 -2.326079000 2.693945000 0.788444000

6 2.032660000 0.875236000 4.027559000

6 0.758093000 0.475162000 3.711004000

6 -0.271098000 1.402088000 3.594938000

1 -1.262549000 1.089985000 3.296736000

1 -0.214749000 2.347177000 4.118631000

1 0.613232000 -0.514385000 3.292404000

1 2.862557000 0.184807000 3.997593000

1 2.210441000 1.816382000 4.526600000 *

81 Product A ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP FREQ

%output Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1 6 3.683646000 10.059463000 1.902011000

6 3.321741000 8.785103000 2.076838000

6 5.040021000 10.561903000 2.269005000

1 2.323748000 8.436641000 1.852016000

6 4.287358000 7.826472000 2.585036000

6 6.076539000 9.469360000 2.499187000

6 5.578621000 8.128029000 2.810137000

1 6.294890000 7.390460000 3.142667000

1 2.963353000 10.782539000 1.536875000

8 7.266709000 9.719214000 2.457449000

17 3.691537000 6.217474000 2.869277000

6 4.908004000 11.421536000 3.573690000

6 6.175664000 12.098244000 3.984639000

6 6.754189000 11.946057000 5.167239000

1 5.430081000 11.220176000 1.488125000

1 4.136798000 12.172814000 3.376088000

1 4.536137000 10.784822000 4.379554000

1 6.629414000 12.753584000 3.246999000

1 6.341634000 11.282642000 5.919495000

1 7.665535000 12.469554000 5.424882000 *

82 Product B ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP FREQ

%output Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1 6 2.686741000 7.607092000 7.140707000

6 1.434730000 8.319366000 7.291897000

6 3.688382000 7.693720000 8.036738000

1 0.635688000 8.147237000 6.584903000

1 4.597604000 7.115092000 7.944481000

6 1.275798000 9.166215000 8.315261000

6 3.533787000 8.499784000 9.246899000

6 2.370148000 9.494498000 9.277569000

1 2.789127000 6.957651000 6.279175000

8 4.306925000 8.426780000 10.184162000

17 -0.225893000 10.010008000 8.548473000

6 2.932895000 10.919745000 8.934612000

6 3.857548000 11.468385000 9.974842000

6 3.625218000 12.592214000 10.640972000

1 1.982996000 9.529234000 10.296879000

1 2.081859000 11.589659000 8.808501000

1 3.440617000 10.850574000 7.967117000

1 4.753944000 10.895437000 10.181466000

1 2.731925000 13.183102000 10.468911000

1 4.320868000 12.964283000 11.382287000 *

83 5.2.3 Claisen rearrangement of 1-(allyloxy)-3-bromobenzene (1c)

Reactant ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP FREQ

%output Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1 6 -0.020295000 -1.652826000 1.108051000

6 -1.370843000 -1.440185000 1.368069000

6 0.893807000 -1.848285000 2.132283000

1 -2.051994000 -1.301618000 0.542611000

1 1.940233000 -2.015544000 1.925047000

6 -1.818249000 -1.416573000 2.689131000

6 0.422359000 -1.825950000 3.440165000

6 -0.910700000 -1.614316000 3.734498000

1 -1.270374000 -1.596337000 4.752844000

1 0.322219000 -1.668280000 0.081246000

8 -3.104132000 -1.205260000 3.074834000

35 1.653869000 -2.095347000 4.876721000

6 -4.113492000 -0.986912000 2.083211000

6 -4.587834000 -2.263537000 1.460603000

6 -5.859690000 -2.637218000 1.438958000

1 -6.173364000 -3.558553000 0.965230000

1 -6.636707000 -2.031383000 1.892375000

1 -3.828823000 -2.894740000 1.010377000

1 -3.739786000 -0.286352000 1.329186000

84 1 -4.929804000 -0.500450000 2.615657000 *

Transition state A ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP NEB-TS PAL8

%neb nimages = 8 NEB_END_XYZfile = “product.xyz” NEB_TS_XYZfile = “guess1” end

%output Print[ P_Basis ] 3 Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1

6 -1.529905000 1.246938000 -0.533352000

6 -0.273863000 0.688401000 -0.884529000

6 -2.423649000 0.545378000 0.226780000

1 0.331846000 1.166658000 -1.640151000

1 -3.371561000 0.972840000 0.518911000

6 0.005178000 -0.694743000 -0.596802000

6 -2.097484000 -0.777811000 0.613289000

6 -0.934932000 -1.386373000 0.243404000

1 -0.707257000 -2.403759000 0.528354000

1 -1.769939000 2.254315000 -0.850266000

8 1.093656000 -1.234564000 -0.955520000

35 -3.368154000 -1.727839000 1.683735000

6 2.525875000 -0.508946000 0.496862000

6 2.276001000 0.831595000 0.343207000

6 1.067990000 1.385119000 0.753783000

85 1 0.483605000 0.906631000 1.528301000

1 0.868946000 2.436473000 0.602385000

1 2.906834000 1.404560000 -0.327150000

1 1.982316000 -1.096260000 1.222162000

1 3.404712000 -0.969106000 0.069866000 *

Transition state B ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP NEB-TS PAL8

%neb nimages = 8 NEB_END_XYZfile = “product.xyz” NEB_TS_XYZfile = “guess1” end

%output Print[ P_Basis ] 3 Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1

6 0.587617000 4.970447000 2.376878000

6 -0.657874000 4.554993000 1.842084000

6 1.639428000 4.107541000 2.510549000

1 -1.470090000 5.259312000 1.736765000

1 2.592543000 4.434288000 2.905475000

6 -0.801314000 3.253781000 1.454256000

6 1.533689000 2.745880000 2.073828000

6 0.233786000 2.303707000 1.627177000

1 0.172965000 1.348732000 1.129254000

1 0.696935000 6.005417000 2.677398000

8 2.487587000 1.919084000 2.187330000

86 35 -2.463177000 2.647633000 0.727336000

6 2.044813000 0.863248000 4.019412000

6 0.766386000 0.472878000 3.706471000

6 -0.257971000 1.406488000 3.601572000

1 -1.254162000 1.102903000 3.310769000

1 -0.190461000 2.349456000 4.127795000

1 0.612445000 -0.513989000 3.284832000

1 2.870288000 0.167994000 3.978384000

1 2.231882000 1.799594000 4.523867000 *

Product A ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP FREQ

%output Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1 6 -4.537789000 -0.404894000 -3.559402000

6 -3.188391000 -1.001584000 -3.336517000

6 -5.042736000 0.565645000 -2.793504000

1 -3.327721000 -2.061452000 -3.084968000

1 -6.021525000 0.984527000 -2.977288000

6 -2.401193000 -0.414405000 -2.161914000

6 -4.261279000 1.083215000 -1.686178000

6 -3.029991000 0.644058000 -1.372498000

1 -2.459068000 1.049924000 -0.549801000

1 -5.112858000 -0.784724000 -4.396195000

8 -1.283391000 -0.824997000 -1.903809000

35 -5.072561000 2.466915000 -0.658685000

87 6 -2.444671000 0.884962000 -6.297314000

6 -2.058903000 0.413997000 -5.119022000

6 -2.325908000 -0.974904000 -4.627087000

1 -2.993738000 0.269527000 -7.002021000

1 -2.223379000 1.898840000 -6.605373000

1 -1.508931000 1.060754000 -4.440424000

1 -2.826086000 -1.558334000 -5.403403000

1 -1.385308000 -1.473936000 -4.384792000 *

Product B ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP FREQ

%output Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1 6 13.481932000 30.095051000 9.602585000

6 13.198756000 29.715621000 10.863058000

6 14.684543000 29.686188000 8.904450000

1 12.283377000 30.005604000 11.361378000

1 14.823092000 29.986865000 7.875785000

6 14.114263000 28.858459000 11.608177000

6 15.589915000 28.932062000 9.533641000

6 15.468974000 28.520263000 10.962267000

1 12.782280000 30.719828000 9.059547000

8 13.862282000 28.433413000 12.720772000

35 17.153410000 28.344096000 8.614245000

6 16.596949000 29.141674000 11.844099000

6 16.580402000 30.638183000 11.847569000

88 6 17.543039000 31.398867000 11.344215000

1 15.580373000 27.434649000 11.032500000

1 17.559877000 28.774562000 11.489721000

1 16.431907000 28.754793000 12.851705000

1 15.705381000 31.108040000 12.287985000

1 17.484688000 32.479674000 11.370655000

1 18.429942000 30.968450000 10.893051000 *

5.2.4 Claisen rearrangement of 1-(allyloxy)-3-methylbenzene (1e)

Reactant ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP FREQ

%output Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1 6 0.019235000 -1.587324000 1.106343000

6 -1.339989000 -1.411898000 1.357749000

6 0.934914000 -1.672557000 2.141124000

1 -2.029764000 -1.354614000 0.529382000

1 1.987656000 -1.807065000 1.924964000

6 -1.775123000 -1.317061000 2.677579000

6 0.502689000 -1.584410000 3.469065000

6 -0.850010000 -1.406484000 3.720740000

1 -1.218756000 -1.328114000 4.735812000

1 0.358035000 -1.656918000 0.080104000

8 -3.070195000 -1.130239000 3.061933000

6 -4.085098000 -0.989151000 2.066071000

89 6 -4.537617000 -2.308435000 1.519524000

6 -5.802290000 -2.706607000 1.521692000

1 -6.100160000 -3.659959000 1.104266000

1 -6.590000000 -2.089678000 1.940579000

1 -3.766260000 -2.948929000 1.104854000

1 -3.728210000 -0.328490000 1.268728000

1 -4.910913000 -0.487616000 2.570029000

6 1.485273000 -1.700167000 4.603415000

1 1.051769000 -1.355151000 5.542208000

1 1.797950000 -2.738779000 4.742969000

1 2.385286000 -1.114238000 4.407516000

Transition state A ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP NEB-TS PAL8

%neb nimages = 8 NEB_END_XYZfile = “product.xyz” NEB_TS_XYZfile = “guess1” end

%output Print[ P_Basis ] 3 Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1

6 -1.559931000 1.208882000 -0.542358000

6 -0.295618000 0.664988000 -0.888979000

6 -2.434888000 0.494046000 0.224639000

1 0.310189000 1.147157000 -1.642453000

1 -3.387771000 0.924573000 0.508523000

90 6 -0.003057000 -0.709965000 -0.585698000

6 -2.123390000 -0.831767000 0.645085000

6 -0.937666000 -1.397785000 0.257584000

1 -0.685566000 -2.411794000 0.545119000

1 -1.812673000 2.211048000 -0.866973000

8 1.097058000 -1.239151000 -0.938294000

6 2.500611000 -0.511673000 0.516039000

6 2.248536000 0.830704000 0.370717000

6 1.031565000 1.375555000 0.763199000

1 0.435786000 0.891513000 1.525411000

1 0.826591000 2.425125000 0.607337000

1 2.886858000 1.411094000 -0.286177000

1 1.956175000 -1.104455000 1.236153000

1 3.390728000 -0.962583000 0.102502000

6 -3.111411000 -1.578385000 1.497295000

1 -4.083332000 -1.642560000 1.001109000

1 -2.769044000 -2.590630000 1.709627000

1 -3.271743000 -1.065026000 2.449192000 *

Transition state B ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP NEB-TS PAL8

%neb nimages = 8 NEB_END_XYZfile = “product.xyz” NEB_TS_XYZfile = “guess1” end

%output Print[ P_Basis ] 3 Print[ P_Basis ] 2

91 Print[ P_MOs ] 1 end

*xyz 0 1 6 0.615288000 4.902641000 2.338820000

6 -0.636985000 4.503925000 1.808464000

6 1.651977000 4.020362000 2.461221000

1 -1.427192000 5.237536000 1.705986000

1 2.615815000 4.325151000 2.848505000

6 -0.849850000 3.209586000 1.408583000

6 1.508790000 2.664286000 2.019781000

6 0.197136000 2.259293000 1.590310000

1 0.119302000 1.293429000 1.109838000

1 0.748824000 5.935079000 2.639867000

8 2.449840000 1.815423000 2.124636000

6 2.031359000 0.804859000 3.958185000

6 0.733022000 0.442111000 3.691520000

6 -0.267351000 1.401430000 3.589912000

1 -1.278588000 1.112671000 3.339082000

1 -0.165221000 2.351624000 4.096840000

1 0.544167000 -0.546806000 3.288752000

1 2.835421000 0.085645000 3.906488000

1 2.256392000 1.738401000 4.452083000

6 -2.161184000 2.756600000 0.834864000

1 -2.018383000 2.253382000 -0.124634000

1 -2.654771000 2.039500000 1.498658000

1 -2.840335000 3.595172000 0.683131000 *

92 Product A ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP FREQ

%output Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1 6 -2.361512000 -0.339718000 -5.419489000

6 -2.982137000 -1.601301000 -4.913843000

6 -3.074699000 0.764027000 -5.658532000

1 -2.830620000 -2.390806000 -5.661427000

1 -2.587231000 1.665008000 -6.012484000

6 -4.499965000 -1.538788000 -4.714854000

6 -4.517469000 0.807920000 -5.450884000

6 -5.178073000 -0.282682000 -5.005264000

1 -6.248574000 -0.267282000 -4.840701000

1 -1.288914000 -0.339817000 -5.567921000

8 -5.102428000 -2.525552000 -4.322373000

6 -2.316792000 -2.082640000 -3.606465000

6 -0.919542000 -2.613124000 -3.722139000

6 -0.245090000 -2.889945000 -4.831232000

1 -0.654797000 -2.730199000 -5.821068000

1 0.754743000 -3.301563000 -4.787679000

1 -0.437117000 -2.803575000 -2.766752000

1 -2.958629000 -2.863832000 -3.187569000

1 -2.328413000 -1.262288000 -2.880554000

6 -5.216812000 2.098168000 -5.745044000

1 -5.061788000 2.386692000 -6.788893000

1 -6.287153000 2.031020000 -5.557614000

93 1 -4.803506000 2.904604000 -5.132203000

Product B ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP FREQ

%output Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1 6 0.162336000 3.211154000 -1.363061000

6 0.485788000 4.516491000 -1.457613000

6 -1.198162000 2.733836000 -1.489652000

1 1.510907000 4.862226000 -1.442456000

1 -1.361527000 1.664794000 -1.554535000

6 -0.556474000 5.513508000 -1.689152000

6 -2.234608000 3.583558000 -1.598385000

6 -1.995058000 5.058518000 -1.445194000

1 -2.648231000 5.629016000 -2.108636000

1 0.947629000 2.473088000 -1.242453000

8 -0.314437000 6.670722000 -1.983045000

6 -4.620713000 6.247457000 0.594086000

6 -3.685839000 5.308744000 0.511848000

6 -2.293371000 5.549770000 0.020513000

1 -2.076906000 6.619035000 0.027703000

1 -1.578271000 5.059286000 0.686527000

1 -3.921752000 4.298977000 0.833449000

1 -4.422196000 7.270602000 0.293747000

1 -5.613717000 6.030405000 0.966806000

6 -3.621815000 3.121826000 -1.912111000

94 1 -3.900950000 3.454708000 -2.917448000

1 -3.696688000 2.034803000 -1.880526000

1 -4.361649000 3.549368000 -1.234277000

5.2.5 Claisen rearrangement of 1-(allyloxy)-3-ethylbenzene (1f)

Reactant ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP FREQ

%output Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1 6 -0.577492000 -0.857296000 3.753626000

6 -1.938419000 -0.868843000 3.458598000

6 -0.128817000 -0.854988000 5.064079000

1 -2.257480000 -0.876437000 2.427383000

1 0.933540000 -0.845999000 5.274980000

6 -2.858251000 -0.869973000 4.505862000

6 -1.046765000 -0.864349000 6.118576000

6 -2.403774000 -0.869806000 5.825773000

1 -3.140783000 -0.871734000 6.619565000

1 0.136263000 -0.849622000 2.939147000

8 -4.214234000 -0.859417000 4.354524000

6 -4.775554000 -0.937404000 3.043357000

6 -4.761222000 -2.333935000 2.501673000

6 -5.836561000 -2.954088000 2.036039000

1 -5.784339000 -3.958736000 1.636395000

1 -6.810775000 -2.477211000 2.033330000

95 1 -3.800330000 -2.838228000 2.503995000

1 -4.252817000 -0.245167000 2.374505000

1 -5.800337000 -0.583204000 3.151509000

6 -0.574083000 -0.924109000 7.548685000

1 0.363822000 -0.370978000 7.644080000

1 -1.301044000 -0.427009000 8.195464000

6 -0.364326000 -2.365153000 8.031079000

1 0.374575000 -2.877206000 7.411651000

1 -1.295292000 -2.932145000 7.973921000

1 -0.014707000 -2.385816000 9.065433000 *

Transition state A ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP NEB-TS PAL8

%neb nimages = 8 NEB_END_XYZfile = “product.xyz” NEB_TS_XYZfile = “guess1” end

%output Print[ P_Basis ] 3 Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1 6 -1.521375000 1.264192000 -0.496845000

6 -0.264698000 0.729288000 -0.886292000

6 -2.414067000 0.498330000 0.194862000

1 0.354168000 1.264096000 -1.592029000

1 -3.359761000 0.919926000 0.514862000

6 -0.005312000 -0.672729000 -0.709094000

6 -2.135987000 -0.869140000 0.491675000

96 6 -0.958519000 -1.419768000 0.060500000

1 -0.717194000 -2.457047000 0.248946000

1 -1.751445000 2.297904000 -0.725380000

8 1.088216000 -1.190102000 -1.100034000

6 2.480700000 -0.637259000 0.433700000

6 2.269135000 0.719417000 0.399671000

6 1.062349000 1.263252000 0.824644000

1 0.447494000 0.734981000 1.541188000

1 0.888528000 2.327875000 0.757700000

1 2.929943000 1.332395000 -0.203104000

1 1.908355000 -1.270632000 1.095406000

1 3.361643000 -1.079460000 -0.007571000

6 -3.178763000 -1.647687000 1.259736000

1 -3.407966000 -1.093624000 2.176544000

1 -4.106484000 -1.633742000 0.676369000

6 -2.825510000 -3.087256000 1.611729000

1 -1.923882000 -3.138537000 2.225294000

1 -2.655834000 -3.688605000 0.716836000

1 -3.638338000 -3.549296000 2.173875000 *

Transition state B ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP NEB-TS PAL8

%neb nimages = 8 NEB_END_XYZfile = “product.xyz” NEB_TS_XYZfile = “guess1” end

%output Print[ P_Basis ] 3

97 Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1

Product A ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP FREQ

%output Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1 6 -4.724515000 5.285743000 2.148579000

6 -4.698567000 3.931292000 1.522871000

6 -4.911438000 6.399727000 1.435688000

1 -4.933163000 7.365951000 1.925977000

6 -4.861966000 3.914747000 0.000657000

6 -5.084151000 6.365433000 -0.012184000

6 -5.056352000 5.189606000 -0.677108000

1 -5.182899000 5.146341000 -1.752266000

1 -4.603943000 5.333252000 3.224332000

8 -4.832347000 2.853760000 -0.602869000

6 -5.324113000 7.669318000 -0.717677000

1 -4.570299000 8.393399000 -0.391281000

1 -5.195691000 7.532827000 -1.792569000

6 -6.722190000 8.235539000 -0.431702000

1 -6.881466000 8.387036000 0.637272000

1 -7.493093000 7.552015000 -0.791098000

1 -6.855689000 9.196337000 -0.931189000

6 -5.749417000 2.982288000 2.164409000

98 6 -5.451750000 2.665805000 3.594403000

6 -6.233814000 2.960657000 4.625257000

1 -3.714772000 3.481531000 1.713586000

1 -5.738350000 2.069047000 1.564564000

1 -6.741440000 3.430702000 2.071627000

1 -4.509339000 2.153127000 3.775819000

1 -7.179672000 3.473628000 4.489207000

1 -5.964939000 2.692344000 5.639033000 *

Product B ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP FREQ

%output Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1 6 -10.540231000 7.163715000 1.468838000

6 -11.496649000 6.225394000 1.331460000

6 -9.201268000 6.850752000 1.910067000

1 -12.504299000 6.463479000 1.017432000

1 -8.507173000 7.672423000 2.045332000

6 -11.205245000 4.827871000 1.612197000

6 -8.802530000 5.594878000 2.175977000

6 -9.767027000 4.447320000 2.007401000

1 -10.773710000 8.201905000 1.259633000

8 -12.055802000 3.956483000 1.530010000

6 -7.397060000 5.334966000 2.657468000

1 -7.074261000 6.198658000 3.243819000

1 -7.385496000 4.474128000 3.326311000

99 6 -6.378744000 5.106847000 1.530844000

1 -6.368738000 5.953669000 0.842466000

1 -6.602528000 4.206267000 0.961498000

1 -5.376365000 4.993504000 1.947910000

6 -9.274446000 3.364586000 1.009726000

6 -8.359080000 2.292803000 1.527741000

6 -8.159807000 1.922190000 2.785185000

1 -9.881385000 3.962529000 2.983945000

1 -8.810053000 3.858258000 0.151973000

1 -10.168301000 2.864335000 0.624916000

1 -7.851647000 1.733821000 0.745186000

1 -8.634269000 2.416394000 3.624118000

1 -7.510243000 1.090501000 3.024542000 *

5.2.6 Claisen rearrangement of 1-(allyloxy)-3- (trifluoromethyl)benzene (1i)

Reactant ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP FREQ

%output Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1 6 -2.456451000 -0.683868000 4.575215000

6 -3.277159000 -1.415322000 3.722549000

6 -2.505588000 -0.865531000 5.948088000

1 -3.216304000 -1.245216000 2.658290000

1 -1.864095000 -0.297000000 6.605126000

6 -4.164875000 -2.352116000 4.253469000

100 6 -3.394827000 -1.803828000 6.468063000

6 -4.220272000 -2.541308000 5.635131000

1 -4.908523000 -3.273554000 6.033072000

1 -1.769576000 0.038406000 4.153613000

8 -5.003109000 -3.133838000 3.524612000

6 -3.504318000 -1.993630000 7.956291000

9 -4.497476000 -1.239735000 8.484788000

9 -3.776502000 -3.272125000 8.289457000

9 -2.370773000 -1.647666000 8.598990000

6 -5.048224000 -2.988610000 2.100416000

6 -5.855205000 -1.801500000 1.674019000

6 -6.885719000 -1.878620000 0.843431000

1 -4.028489000 -2.945683000 1.703726000

1 -5.506987000 -3.908276000 1.740012000

1 -5.556318000 -0.840434000 2.079661000

1 -7.214492000 -2.827394000 0.433402000

1 -7.437612000 -0.998660000 0.539092000 *

Transition state A ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP NEB-TS PAL8

%neb nimages = 8 NEB_END_XYZfile = “product.xyz” NEB_TS_XYZfile = “guess1” end

%output Print[ P_Basis ] 3 Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

101 *xyz 0 1 6 -1.561069000 1.150033000 -0.602584000

6 -0.279542000 0.610463000 -0.897420000

6 -2.446192000 0.455682000 0.168738000

1 0.327965000 1.069612000 -1.663747000

1 -3.410896000 0.873529000 0.421123000

6 0.029389000 -0.752008000 -0.546363000

6 -2.100738000 -0.842474000 0.634053000

6 -0.910558000 -1.425955000 0.308261000

1 -0.658914000 -2.420850000 0.647644000

1 -1.818825000 2.134686000 -0.971899000

8 1.134877000 -1.279030000 -0.861907000

6 2.528518000 -0.437672000 0.594830000

6 2.230314000 0.880631000 0.367660000

6 0.992213000 1.409383000 0.725258000

1 1.986760000 -1.013350000 1.330701000

1 3.433194000 -0.884103000 0.209077000

1 2.854353000 1.444374000 -0.316674000

1 0.412106000 0.951847000 1.515524000

1 0.764762000 2.446579000 0.524324000

6 -3.109040000 -1.569217000 1.481743000

9 -3.505694000 -0.810719000 2.530010000

9 -4.225509000 -1.866630000 0.778506000

9 -2.638896000 -2.723766000 1.984462000

Transition state B ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP NEB-TS PAL8

102

%neb nimages = 8 NEB_END_XYZfile = “product.xyz” NEB_TS_XYZfile = “guess1” end

%output Print[ P_Basis ] 3 Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1 6 0.580090000 4.960849000 2.318408000

6 1.613165000 4.081071000 2.468172000

6 -0.663795000 4.549024000 1.775966000

1 2.572946000 4.396699000 2.857120000

1 -1.453844000 5.271300000 1.630747000

6 1.488127000 2.709806000 2.055051000

6 -0.843785000 3.242796000 1.414651000

6 0.179995000 2.278818000 1.635110000

1 0.105964000 1.313797000 1.156311000

1 0.706823000 5.998635000 2.600812000

8 2.440027000 1.884375000 2.171097000

6 2.016581000 0.878157000 4.046759000

6 0.732255000 0.496708000 3.754818000

6 -0.287430000 1.436930000 3.639372000

1 2.834248000 0.173403000 4.014172000

1 2.220653000 1.828262000 4.517454000

1 0.561592000 -0.498859000 3.360923000

1 -1.288575000 1.124535000 3.382163000

1 -0.210243000 2.389321000 4.147150000

103 6 -2.132153000 2.779021000 0.798403000

9 -2.962585000 3.792440000 0.498037000

9 -1.915229000 2.084723000 -0.340702000

9 -2.818650000 1.943402000 1.620706000

Product A ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP FREQ

%output Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1

6 -0.689679000 -3.734927000 3.646803000

6 0.347862000 -2.889535000 2.983777000

6 -1.998115000 -3.525972000 3.477118000

1 1.160661000 -2.658192000 3.675939000

1 -2.733880000 -4.177783000 3.927910000

6 -0.178992000 -1.572533000 2.433724000

6 -2.461259000 -2.405091000 2.672844000

6 -1.621199000 -1.490305000 2.160437000

1 -1.969878000 -0.635221000 1.599073000

1 -0.342441000 -4.577547000 4.233234000

8 0.561426000 -0.636609000 2.198482000

6 -3.948131000 -2.303326000 2.450318000

9 -4.607842000 -2.213321000 3.625190000

9 -4.300188000 -1.243947000 1.708316000

9 -4.411229000 -3.407854000 1.824356000

6 3.374838000 -3.663283000 1.152188000

104 6 2.180593000 -3.086236000 1.189842000

6 0.972183000 -3.719063000 1.804162000

1 3.546837000 -4.646797000 1.576618000

1 4.223814000 -3.175365000 0.690843000

1 2.048551000 -2.098188000 0.764142000

1 0.190330000 -3.865845000 1.051999000

1 1.230161000 -4.706437000 2.192399000 *

Product B ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP FREQ

%output Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1

6 -0.689679000 -3.734927000 3.646803000

6 0.347862000 -2.889535000 2.983777000

6 -1.998115000 -3.525972000 3.477118000

1 1.160661000 -2.658192000 3.675939000

1 -2.733880000 -4.177783000 3.927910000

6 -0.178992000 -1.572533000 2.433724000

6 -2.461259000 -2.405091000 2.672844000

6 -1.621199000 -1.490305000 2.160437000

1 -1.969878000 -0.635221000 1.599073000

1 -0.342441000 -4.577547000 4.233234000

8 0.561426000 -0.636609000 2.198482000

6 -3.948131000 -2.303326000 2.450318000

9 -4.607842000 -2.213321000 3.625190000

9 -4.300188000 -1.243947000 1.708316000

105 9 -4.411229000 -3.407854000 1.824356000

6 3.374838000 -3.663283000 1.152188000

6 2.180593000 -3.086236000 1.189842000

6 0.972183000 -3.719063000 1.804162000

1 3.546837000 -4.646797000 1.576618000

1 4.223814000 -3.175365000 0.690843000

1 2.048551000 -2.098188000 0.764142000

1 0.190330000 -3.865845000 1.051999000

1 1.230161000 -4.706437000 2.192399000 *

5.2.7 Claisen rearrangement of 4-(allyloxy)-1-fluoro-2- methylbenzene (2a)

Reactant ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP FREQ

%output Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1 6 -10.592196000 0.259815000 7.695409000

6 -11.919862000 0.652121000 7.529542000

6 -10.282849000 -0.717153000 8.614044000

1 -12.156810000 1.415448000 6.804470000

6 -12.909482000 0.049123000 8.300884000

6 -11.248288000 -1.348233000 9.396078000

6 -12.564509000 -0.944127000 9.221035000

1 -13.354422000 -1.399604000 9.804580000

1 -9.801892000 0.712328000 7.111939000

8 -14.236848000 0.354779000 8.232197000

106 6 -10.862573000 -2.415322000 10.379197000

1 -11.737943000 -2.779657000 10.915319000

1 -10.390082000 -3.261267000 9.875177000

1 -10.142391000 -2.037486000 11.107769000

9 -8.984707000 -1.085532000 8.768196000

6 -14.647563000 1.383276000 7.334628000

6 -16.113033000 1.597037000 7.516008000

6 -16.994193000 1.563792000 6.526704000

1 -14.099049000 2.305539000 7.566263000

1 -14.420146000 1.101950000 6.300729000

1 -16.432384000 1.806861000 8.532127000

1 -16.694690000 1.343528000 5.508001000

1 -18.045331000 1.758471000 6.696113000 *

Transition state A ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP NEB-TS PAL8

%neb nimages = 8 NEB_END_XYZfile = “product.xyz” NEB_TS_XYZfile = “guess1” end

%output Print[ P_Basis ] 3 Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1 6 -1.559627000 1.029611000 -0.695181000

6 -0.250685000 0.515398000 -0.886816000

6 -2.385694000 0.411149000 0.188488000

1 0.338124000 0.864252000 -1.722096000

107 6 0.120728000 -0.743451000 -0.296130000

6 -2.027499000 -0.762108000 0.904953000

6 -0.790757000 -1.299259000 0.664613000

1 -0.480024000 -2.204425000 1.172145000

1 -1.896728000 1.913688000 -1.219757000

8 1.254520000 -1.265987000 -0.520177000

6 2.605081000 -0.148275000 0.753206000

6 2.260126000 1.105019000 0.313452000

6 1.004283000 1.639945000 0.579340000

1 2.089284000 -0.608878000 1.582624000

1 3.526177000 -0.618428000 0.441668000

1 2.864546000 1.567725000 -0.458930000

1 0.434238000 1.296779000 1.432305000

1 0.733825000 2.615343000 0.200712000

6 -3.002066000 -1.366775000 1.872445000

1 -3.924613000 -1.661525000 1.367399000

1 -2.571744000 -2.245209000 2.350926000

1 -3.283033000 -0.649267000 2.646553000

9 -3.626814000 0.911906000 0.404143000

Transition state B ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP NEB-TS PAL8

%neb nimages = 8 NEB_END_XYZfile = “product.xyz” NEB_TS_XYZfile = “guess1” end

108 %output Print[ P_Basis ] 3 Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1 6 0.567437000 4.955550000 2.343568000

6 1.611325000 4.086536000 2.488905000

6 -0.652918000 4.509556000 1.797103000

1 2.562616000 4.411609000 2.889257000

6 1.493952000 2.722735000 2.057553000

6 -0.872650000 3.219962000 1.405344000

6 0.189825000 2.295283000 1.621481000

1 0.129362000 1.325340000 1.147880000

1 0.651802000 5.996511000 2.628754000

8 2.448173000 1.894131000 2.173561000

6 2.030598000 0.869012000 4.031251000

6 0.743087000 0.491785000 3.741270000

6 -0.270219000 1.436582000 3.623336000

1 2.844237000 0.159451000 3.997175000

1 2.238051000 1.812327000 4.514067000

1 0.570611000 -0.503303000 3.346354000

1 -1.275092000 1.131944000 3.366688000

1 -0.187333000 2.389801000 4.127898000

6 -2.170199000 2.777968000 0.794789000

1 -2.149310000 2.896916000 -0.292341000

1 -2.355283000 1.723153000 1.002717000

1 -3.009362000 3.361784000 1.170684000

9 -1.637995000 5.431892000 1.651310000

109 *

Product A ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP FREQ

%output Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1 6 -15.391343000 1.469720000 7.563030000

6 -14.256484000 0.503825000 7.685569000

6 -16.627780000 1.040508000 7.334333000

1 -14.043289000 0.422250000 8.763472000

6 -14.591308000 -0.942610000 7.301142000

6 -16.983517000 -0.353576000 7.120735000

6 -16.000946000 -1.280012000 7.109056000

1 -16.220476000 -2.323150000 6.919054000

1 -15.198889000 2.527237000 7.691928000

8 -13.710886000 -1.779192000 7.210964000

6 -18.424141000 -0.693733000 6.901171000

1 -18.552884000 -1.766610000 6.772444000

1 -19.031562000 -0.361382000 7.746135000

1 -18.813018000 -0.179801000 6.019063000

9 -17.657679000 1.919515000 7.260547000

6 -13.973292000 0.982422000 4.723577000

6 -12.977737000 1.233076000 5.562671000

6 -12.949388000 0.992276000 7.042750000

1 -13.874707000 1.185480000 3.665035000

1 -14.916567000 0.561044000 5.045207000

1 -12.056253000 1.648999000 5.163422000

110 1 -12.176777000 0.250226000 7.260752000

1 -12.635711000 1.913803000 7.545226000 *

Product B ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP FREQ

%output Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1

6 -15.201566000 1.171174000 6.228864000

6 -14.760218000 0.286336000 5.316619000

6 -16.236852000 0.833862000 7.168732000

1 -13.963915000 0.521834000 4.623549000

6 -15.327311000 -1.059422000 5.247334000

6 -16.861225000 -0.346748000 7.214934000

6 -16.508244000 -1.382986000 6.177018000

1 -17.363629000 -1.403783000 5.483360000

1 -14.779074000 2.166442000 6.299306000

8 -14.918186000 -1.892836000 4.459903000

6 -17.922796000 -0.662527000 8.217516000

1 -18.809025000 -1.075214000 7.727641000

1 -17.565173000 -1.414471000 8.926220000

1 -18.214843000 0.222255000 8.778113000

9 -16.540135000 1.821138000 8.052296000

6 -14.418718000 -2.193749000 8.186677000

6 -15.338675000 -3.051103000 7.764910000

6 -16.393799000 -2.816922000 6.725684000

1 -13.690178000 -2.480490000 8.933968000

111 1 -14.342610000 -1.183545000 7.807187000

1 -15.346813000 -4.052283000 8.188154000

1 -16.195058000 -3.470450000 5.872431000

1 -17.362198000 -3.131129000 7.124767000 *

5.2.8 Claisen rearrangement of 4-(allyloxy)-1-chloro-2- methylbenzene (2b)

Reactant ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP FREQ

%output Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1 6 -3.499563000 -1.633648000 11.828068000

6 -4.225705000 -2.182282000 12.869705000

6 -2.654029000 -0.552009000 12.050810000

1 -2.104722000 -0.138116000 11.219086000

6 -4.134707000 -1.671637000 14.169942000

6 -2.541616000 -0.028541000 13.336704000

6 -3.284701000 -0.592496000 14.375147000

1 -3.180968000 -0.167152000 15.365038000

1 -3.594631000 -2.048959000 10.834406000

8 -1.739485000 1.013962000 13.689043000

6 -4.917821000 -2.259102000 15.307357000

1 -5.990379000 -2.219907000 15.106745000

1 -4.664307000 -3.310977000 15.455200000

1 -4.717790000 -1.720348000 16.232432000

17 -5.278256000 -3.541660000 12.537725000

112 6 -0.938198000 1.651753000 12.690701000

6 -1.721676000 2.625655000 11.865808000

6 -1.383105000 3.899244000 11.719742000

1 -0.458859000 0.891503000 12.064728000

1 -0.155331000 2.169136000 13.244098000

1 -2.608008000 2.239587000 11.373133000

1 -0.509313000 4.313260000 12.211148000

1 -1.961524000 4.574178000 11.101978000 *

Transition state A ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP NEB-TS PAL8

%neb nimages = 8 NEB_END_XYZfile = “product.xyz” NEB_TS_XYZfile = “guess1” end

%output Print[ P_Basis ] 3 Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1 6 -1.649296000 0.895295000 -0.800764000

6 -0.362371000 0.341394000 -1.011209000

6 -2.493036000 0.331851000 0.112024000

1 0.219333000 0.663080000 -1.862534000

6 -0.014316000 -0.915396000 -0.403475000

6 -2.144468000 -0.848888000 0.837008000

6 -0.928332000 -1.425171000 0.577501000

1 -0.637746000 -2.333082000 1.092064000

1 -1.954111000 1.780126000 -1.342942000

113 8 1.100694000 -1.471742000 -0.633308000

6 2.503590000 -0.344225000 0.592385000

6 2.173477000 0.906232000 0.135281000

6 0.932921000 1.469228000 0.415879000

1 1.995280000 -0.780129000 1.439484000

1 3.409233000 -0.837950000 0.271977000

1 2.771881000 1.344558000 -0.655662000

1 0.372021000 1.150077000 1.284010000

1 0.673889000 2.443693000 0.027073000

6 -3.087341000 -1.442866000 1.841235000

1 -4.032583000 -1.725355000 1.372804000

1 -2.648076000 -2.327092000 2.300467000

1 -3.330386000 -0.723794000 2.626436000

17 -4.056218000 1.068117000 0.388929000

Transition state B ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP NEB-TS PAL8

%neb nimages = 8 NEB_END_XYZfile = “product.xyz” NEB_TS_XYZfile = “guess1” end

%output Print[ P_Basis ] 3 Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1 6 0.592493000 4.953274000 2.301730000

6 1.630972000 4.082651000 2.463660000

114 6 -0.640466000 4.518174000 1.758855000

1 2.581914000 4.411738000 2.861921000

6 1.508780000 2.713338000 2.056425000

6 -0.852643000 3.215908000 1.381059000

6 0.205646000 2.291063000 1.614137000

1 0.142746000 1.314725000 1.154716000

1 0.694602000 5.994613000 2.577120000

8 2.453179000 1.878531000 2.193451000

6 1.992327000 0.875896000 4.065161000

6 0.703376000 0.514165000 3.764114000

6 -0.295161000 1.471943000 3.626109000

1 2.796331000 0.154931000 4.046794000

1 2.209049000 1.823060000 4.536219000

1 0.519820000 -0.483304000 3.380565000

1 -1.302222000 1.180821000 3.362151000

1 -0.200668000 2.431380000 4.116900000

6 -2.149719000 2.738150000 0.799451000

1 -2.445095000 3.344087000 -0.058696000

1 -2.070943000 1.699716000 0.479519000

1 -2.960564000 2.812937000 1.529400000

17 -1.907700000 5.710369000 1.573679000

Product A ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP FREQ

%output Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

115 *xyz 0 1 6 -1.282997000 1.517854000 12.105775000

6 -0.894892000 1.223831000 13.347463000

6 -2.253180000 0.665581000 11.360628000

1 -3.098763000 1.288108000 11.043578000

6 -1.397972000 0.059568000 14.082966000

6 -2.854804000 -0.484200000 12.162708000

6 -2.320538000 -0.733492000 13.495233000

1 -2.718744000 -1.596448000 14.014129000

1 -0.869017000 2.375165000 11.592169000

8 -3.740077000 -1.169595000 11.679050000

6 -0.888860000 -0.227745000 15.459903000

1 0.196145000 -0.352000000 15.454525000

1 -1.101570000 0.605308000 16.133456000

1 -1.347466000 -1.130787000 15.857962000

17 0.272584000 2.253731000 14.153904000

6 -0.060348000 1.473494000 8.663593000

6 -1.284212000 1.149552000 9.060515000

6 -1.609186000 0.090288000 10.063693000

1 0.112886000 2.248804000 7.928293000

1 0.813802000 0.966281000 9.057295000

1 -2.136239000 1.683686000 8.645849000

1 -0.710673000 -0.470541000 10.331502000

1 -2.335125000 -0.614551000 9.650986000 *

Product B ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP FREQ

116 %output Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1

6 0.945720000 0.941225000 11.367101000

6 0.545244000 -0.436269000 11.561189000

6 0.076929000 1.959654000 11.500238000

1 0.387830000 2.992654000 11.420209000

6 -0.725922000 -0.806626000 11.785295000

6 -1.316648000 1.694796000 11.851094000

6 -1.792848000 0.251724000 11.712538000

1 -2.544372000 0.076172000 12.485072000

1 1.989976000 1.129863000 11.152232000

8 -2.095179000 2.573718000 12.172415000

6 -1.123722000 -2.215741000 12.101757000

1 -0.597899000 -2.565430000 12.993980000

1 -2.194197000 -2.293922000 12.277218000

1 -0.852475000 -2.900088000 11.294410000

17 1.841338000 -1.614085000 11.558129000

6 -4.582523000 -1.181006000 10.025949000

6 -3.260978000 -1.059446000 10.029518000

6 -2.540369000 0.216515000 10.330094000

1 -5.066003000 -2.121003000 9.792340000

1 -5.228853000 -0.340032000 10.252145000

1 -2.650564000 -1.923871000 9.789554000

1 -3.248427000 1.046480000 10.344462000

117 1 -1.800749000 0.419673000 9.549787000 *

5.2.9 Claisen rearrangement of 4-(allyloxy)-1,2- dimethylbenzene (2c)

Reactant ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP FREQ

%output Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1 6 -10.340318000 -5.310960000 1.809456000

6 -10.439875000 -4.751648000 3.072256000

6 -11.053388000 -6.454616000 1.450085000

1 -9.881448000 -3.865134000 3.341580000

6 -11.272239000 -5.340329000 4.020146000

6 -11.890483000 -7.042651000 2.407501000

6 -11.994101000 -6.481675000 3.681099000

1 -12.659529000 -6.943080000 4.394430000

1 -9.689253000 -4.845334000 1.078662000

8 -11.298159000 -4.738070000 5.248057000

6 -12.689753000 -8.273710000 2.075797000

1 -13.292030000 -8.593025000 2.925936000

1 -13.363925000 -8.096747000 1.233207000

1 -12.041598000 -9.106880000 1.790645000

6 -10.926962000 -7.030699000 0.066154000

1 -11.888941000 -7.047544000 -0.454303000

1 -10.233746000 -6.444498000 -0.536940000

1 -10.561847000 -8.061638000 0.086839000

118 6 -12.185001000 -5.228106000 6.249192000

6 -13.616057000 -4.864788000 5.989124000

6 -14.642877000 -5.683701000 6.165831000

1 -14.500741000 -6.711577000 6.482872000

1 -15.663278000 -5.360299000 6.005962000

1 -13.778047000 -3.842210000 5.661235000

1 -11.840991000 -4.740613000 7.164019000

1 -12.068396000 -6.308366000 6.383352000 *

Transition state A ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP NEB-TS PAL8

%neb nimages = 8 NEB_END_XYZfile = “product.xyz” NEB_TS_XYZfile = “guess1” end

%output Print[ P_Basis ] 3 Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1 6 -1.552149000 1.263410000 -0.479072000

6 -0.293169000 0.724963000 -0.846609000

6 -2.457854000 0.546891000 0.257622000

1 0.314316000 1.235152000 -1.580098000

6 -0.013217000 -0.661952000 -0.603375000

6 -2.139580000 -0.805187000 0.622107000

6 -0.957480000 -1.364288000 0.213666000

1 -0.719131000 -2.390956000 0.466012000

1 -1.788222000 2.281904000 -0.766316000

119 8 1.078710000 -1.192880000 -0.979345000

6 2.491542000 -0.553290000 0.503089000

6 2.261088000 0.797615000 0.409737000

6 1.053601000 1.346913000 0.824919000

1 1.937585000 -1.163091000 1.201463000

1 3.371752000 -1.003882000 0.068780000

1 2.905333000 1.390231000 -0.230415000

1 0.453670000 0.845854000 1.572810000

1 0.866111000 2.404878000 0.708627000

6 -3.772074000 1.153396000 0.663126000

1 -4.618071000 0.586410000 0.264896000

1 -3.891233000 1.173043000 1.750047000

1 -3.853487000 2.177192000 0.299009000

6 -3.116745000 -1.606840000 1.436663000

1 -4.071295000 -1.717326000 0.914975000

1 -2.726988000 -2.602622000 1.642951000

1 -3.335127000 -1.121218000 2.391446000

Transition state B ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP NEB-TS PAL8

%neb nimages = 8 NEB_END_XYZfile = “product.xyz” NEB_TS_XYZfile = “guess1” end

%output Print[ P_Basis ] 3 Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

120 *xyz 0 1 6 0.601199000 4.887158000 2.434988000

6 1.620847000 3.991649000 2.596711000

6 -0.677336000 4.516271000 1.937257000

1 2.592661000 4.300140000 2.960613000

6 1.446362000 2.619170000 2.231000000

6 -0.907359000 3.194972000 1.614031000

6 0.116697000 2.232814000 1.837951000

1 0.005726000 1.245592000 1.410776000

1 0.766794000 5.929944000 2.683560000

8 2.366493000 1.753903000 2.364897000

6 1.938857000 0.846222000 4.278268000

6 0.630057000 0.511222000 4.035982000

6 -0.345291000 1.491739000 3.886141000

1 2.719910000 0.100321000 4.267081000

1 2.197589000 1.803905000 4.704795000

1 0.407133000 -0.494404000 3.696722000

1 -1.365704000 1.215336000 3.660262000

1 -0.214902000 2.465291000 4.339535000

6 -2.232285000 2.739179000 1.068705000

1 -2.253718000 1.657298000 0.939447000

1 -3.058534000 3.017848000 1.728962000

1 -2.440472000 3.195631000 0.096814000

6 -1.740551000 5.565486000 1.755537000

1 -2.038566000 5.658977000 0.707234000

1 -2.646340000 5.326466000 2.319798000

1 -1.388966000 6.541709000 2.088590000

121 *

Product A ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP FREQ

%output Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1

6 -12.696729000 -5.756058000 5.294784000

6 -11.871537000 -6.108198000 4.104542000

6 -12.276959000 -5.872713000 6.561711000

1 -12.378795000 -6.913774000 3.556045000

6 -10.480877000 -6.651947000 4.421102000

6 -10.926233000 -6.391544000 6.832541000

6 -10.103462000 -6.749702000 5.822192000

1 -9.107477000 -7.127038000 6.019710000

1 -13.685795000 -5.359799000 5.093437000

8 -9.727545000 -6.985155000 3.519605000

6 -10.470700000 -6.511923000 8.256392000

1 -9.461742000 -6.916369000 8.311202000

1 -10.480843000 -5.539714000 8.755736000

1 -11.136271000 -7.163630000 8.828057000

6 -13.158408000 -5.475323000 7.713780000

1 -12.698549000 -4.692800000 8.322616000

1 -14.114178000 -5.100443000 7.349732000

1 -13.358302000 -6.318533000 8.379827000

6 -11.749972000 -4.910988000 3.120419000

6 -13.055175000 -4.543819000 2.492034000

122 6 -13.688731000 -3.389889000 2.660090000

1 -13.277914000 -2.606063000 3.287283000

1 -14.632123000 -3.181853000 2.171428000

1 -13.503152000 -5.305526000 1.857346000

1 -11.031606000 -5.213772000 2.354859000

1 -11.330639000 -4.053533000 3.652197000 *

Product B ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP FREQ

%output Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1

6 -12.918543000 -4.293394000 6.061919000

6 -13.175473000 -5.369631000 5.295967000

6 -11.584470000 -3.835516000 6.421291000

1 -14.183685000 -5.691140000 5.069059000

6 -12.083172000 -6.161901000 4.753861000

6 -10.507197000 -4.500614000 5.960381000

6 -10.663075000 -5.663767000 5.017470000

1 -10.122935000 -6.521998000 5.433089000

1 -13.752042000 -3.722703000 6.460247000

8 -12.264705000 -7.172437000 4.093258000

6 -9.091168000 -4.127237000 6.292609000

1 -8.441524000 -5.003434000 6.254206000

1 -8.696836000 -3.402517000 5.573115000

1 -9.001010000 -3.688449000 7.284496000

6 -11.524764000 -2.618518000 7.305620000

123 1 -10.513819000 -2.244075000 7.442246000

1 -12.118721000 -1.809311000 6.872259000

1 -11.946401000 -2.827737000 8.293407000

6 -9.990013000 -5.363469000 3.641480000

6 -10.566412000 -4.160656000 2.963813000

6 -9.875357000 -3.081983000 2.618785000

1 -8.809875000 -3.006447000 2.808254000

1 -10.344038000 -2.240009000 2.125480000

1 -11.632120000 -4.196082000 2.754229000

1 -10.146556000 -6.254220000 3.028471000

1 -8.915355000 -5.236591000 3.778864000 *

5.2.10 Claisen rearrangement of 4-(allyloxy)-2-chloro-1- fluorobenzene (3a)

Reactant ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP FREQ

%output Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1 6 -1.871836000 -0.070161000 3.012016000

6 -3.140323000 0.231848000 3.499543000

6 -0.841776000 0.837630000 3.140806000

1 -3.930803000 -0.492517000 3.378358000

6 -3.366264000 1.457656000 4.124752000

6 -1.061299000 2.064787000 3.759988000

6 -2.318804000 2.372461000 4.248958000

1 -2.499519000 3.321737000 4.731969000

124 1 -1.677310000 -1.015426000 2.523707000

8 -4.553199000 1.861826000 4.653846000

17 0.239612000 3.200467000 3.915213000

9 0.378039000 0.534320000 2.661999000

6 -5.700176000 1.013493000 4.541931000

6 -6.343188000 1.100849000 3.192286000

6 -7.628212000 1.371864000 3.010280000

1 -5.421286000 -0.016459000 4.788721000

1 -6.386537000 1.364814000 5.311292000

1 -5.698936000 0.925229000 2.336867000

1 -8.291829000 1.563211000 3.846571000

1 -8.067267000 1.409002000 2.021686000 *

Transition state A ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP NEB-TS PAL8

%neb nimages = 8 NEB_END_XYZfile = “product.xyz” NEB_TS_XYZfile = “guess1” end

%output Print[ P_Basis ] 3 Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1 6 -1.564620000 1.236238000 -0.514037000

6 -0.301650000 0.683800000 -0.851843000

6 -2.438894000 0.512414000 0.234129000

1 0.293133000 1.163250000 -1.614936000

6 -0.018018000 -0.699839000 -0.567682000

125 6 -2.131403000 -0.811425000 0.647133000

6 -0.954710000 -1.392916000 0.274903000

1 -0.724340000 -2.407754000 0.567012000

1 -1.838318000 2.235444000 -0.825862000

8 1.064896000 -1.241662000 -0.934662000

6 2.528492000 -0.515331000 0.508553000

6 2.270125000 0.820838000 0.342064000

6 1.066221000 1.377692000 0.762917000

1 1.990281000 -1.099592000 1.240368000

1 3.401952000 -0.978386000 0.073699000

1 2.892009000 1.389236000 -0.340529000

1 0.496765000 0.908182000 1.554024000

1 0.866308000 2.428275000 0.606771000

17 -3.287666000 -1.666265000 1.617388000

9 -3.627583000 1.032511000 0.580676000

Transition state B ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP NEB-TS PAL8

%neb nimages = 8 NEB_END_XYZfile = “product.xyz” NEB_TS_XYZfile = “guess1” end

%output Print[ P_Basis ] 3 Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1 6 0.723714000 4.982197000 1.927729000

126 6 1.731386000 4.070030000 2.061314000

6 -0.567257000 4.575760000 1.532678000

1 2.728973000 4.375469000 2.347356000

6 1.515843000 2.681929000 1.765969000

6 -0.846242000 3.262530000 1.280925000

6 0.161329000 2.282681000 1.472961000

1 0.003675000 1.296492000 1.064675000

1 0.884663000 6.036713000 2.112142000

8 2.435337000 1.817126000 1.876499000

6 2.117570000 0.954438000 3.834145000

6 0.803196000 0.601908000 3.653824000

6 -0.188915000 1.569938000 3.548551000

1 2.907430000 0.218869000 3.793904000

1 2.383528000 1.921141000 4.235858000

1 0.576457000 -0.408913000 3.333920000

1 -1.216926000 1.288134000 3.366796000

1 -0.042785000 2.547242000 3.989452000

17 -2.435313000 2.768475000 0.794225000

9 -1.514877000 5.519810000 1.403677000

Product A ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP FREQ

%output Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1

6 -6.825633000 -1.721615000 -0.218227000

127 6 -7.935829000 -2.617010000 -0.656225000

6 -6.907995000 -0.999855000 0.894566000

1 -7.565448000 -3.651061000 -0.657347000

6 -9.161204000 -2.640175000 0.261113000

6 -8.072985000 -1.051254000 1.767897000

6 -9.134373000 -1.823547000 1.473957000

1 -10.004119000 -1.856293000 2.114393000

1 -5.946032000 -1.644165000 -0.844042000

8 -10.126305000 -3.327755000 -0.019017000

17 -8.041793000 -0.075703000 3.192056000

9 -5.915924000 -0.174870000 1.267325000

6 -6.660792000 -1.785354000 -3.872991000

6 -7.318866000 -2.652685000 -3.114227000

6 -8.372173000 -2.298374000 -2.114289000

1 -5.909113000 -2.107144000 -4.582386000

1 -6.858896000 -0.720438000 -3.818481000

1 -7.087950000 -3.712413000 -3.197892000

1 -8.627650000 -1.238687000 -2.186021000

1 -9.280626000 -2.876342000 -2.296994000 *

Product B ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP FREQ

%output Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1

6 -6.837339000 -2.686390000 -2.016773000

6 -8.161223000 -2.852114000 -1.853162000

128 6 -6.007043000 -2.098498000 -0.996090000

1 -8.781532000 -3.310922000 -2.610851000

6 -8.817725000 -2.432746000 -0.616155000

6 -6.504793000 -1.656255000 0.162149000

6 -7.973331000 -1.703430000 0.443143000

1 -8.128805000 -2.250578000 1.378271000

1 -6.334431000 -3.003385000 -2.922440000

8 -10.002508000 -2.619386000 -0.413314000

17 -5.473919000 -0.992488000 1.376948000

9 -4.694096000 -2.039993000 -1.277393000

6 -7.674797000 1.702297000 -0.579125000

6 -8.415290000 0.602452000 -0.545305000

6 -8.567573000 -0.277673000 0.655648000

1 -7.596517000 2.307201000 -1.473334000

1 -7.122483000 2.039105000 0.291058000

1 -8.952115000 0.294459000 -1.438607000

1 -8.085659000 0.176456000 1.521272000

1 -9.623735000 -0.425306000 0.890481000 *

5.2.11 Claisen rearrangement of 4-(allyloxy)-1,2- dichlorobenzene (3b)

Reactant ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP FREQ

%output Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1 6 -11.176933000 -1.240157000 -1.921646000

129 6 -11.599561000 -1.094066000 -0.607526000

6 -10.274593000 -0.353057000 -2.490657000

1 -12.327132000 -1.783272000 -0.208100000

6 -11.102126000 -0.041981000 0.159156000

6 -9.790264000 0.706194000 -1.719927000

6 -10.200402000 0.857931000 -0.405461000

1 -9.820087000 1.672980000 0.192888000

1 -11.559254000 -2.052609000 -2.523590000

8 -11.429965000 0.198823000 1.457463000

17 -8.665531000 1.852392000 -2.376391000

17 -9.779909000 -0.579491000 -4.138934000

6 -12.234601000 -0.738139000 2.159146000

6 -13.706946000 -0.589599000 1.922341000

6 -14.276346000 0.338555000 1.168076000

1 -11.908376000 -1.760336000 1.933697000

1 -12.014550000 -0.563635000 3.215434000

1 -14.318476000 -1.318234000 2.448128000

1 -15.351373000 0.387806000 1.058190000

1 -13.689305000 1.076831000 0.637479000 *

Transition state A ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP NEB-TS PAL8

%neb nimages = 8 NEB_END_XYZfile = “product.xyz” NEB_TS_XYZfile = “guess1” end

%output Print[ P_Basis ] 3

130 Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1 6 -1.553082000 1.228453000 -0.518104000

6 -0.298482000 0.672862000 -0.868503000

6 -2.438357000 0.526853000 0.250762000

1 0.296412000 1.155527000 -1.629680000

6 -0.014673000 -0.709312000 -0.582806000

6 -2.120710000 -0.805010000 0.651896000

6 -0.951264000 -1.393031000 0.262691000

1 -0.726091000 -2.409391000 0.553711000

1 -1.807814000 2.230889000 -0.833926000

8 1.069643000 -1.249940000 -0.946349000

6 2.514737000 -0.512844000 0.513835000

6 2.253744000 0.823243000 0.350090000

6 1.043676000 1.373560000 0.761735000

1 1.971164000 -1.101485000 1.238094000

1 3.395625000 -0.969953000 0.087947000

1 2.878460000 1.395588000 -0.326475000

1 0.466586000 0.896534000 1.542702000

1 0.841352000 2.424141000 0.609474000

17 -3.942681000 1.257188000 0.712999000

17 -3.233455000 -1.699042000 1.639945000

Transition state B ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP NEB-TS PAL8

%neb

131 nimages = 8 NEB_END_XYZfile = “product.xyz” NEB_TS_XYZfile = “guess1” end

%output Print[ P_Basis ] 3 Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1 6 1.473636000 -1.425182000 -0.739069000

6 0.735133000 -1.772998000 0.353873000

6 1.852112000 -0.080137000 -0.981585000

1 0.463477000 -2.803885000 0.538573000

6 0.340021000 -0.791633000 1.322412000

6 1.465474000 0.899685000 -0.103611000

6 0.639966000 0.580613000 1.004817000

1 0.520854000 1.316295000 1.784957000

1 1.794447000 -2.174300000 -1.450408000

8 -0.352498000 -1.083240000 2.341513000

17 1.892239000 2.564102000 -0.339993000

17 2.798325000 0.265153000 -2.391965000

6 -2.382285000 -0.620958000 1.739576000

6 -2.162142000 0.673159000 1.338411000

6 -1.405250000 0.951549000 0.206649000

1 -2.858138000 -0.842624000 2.683315000

1 -2.290009000 -1.442644000 1.045118000

1 -2.353833000 1.474564000 2.043018000

1 -1.194846000 1.971936000 -0.082834000

1 -1.311635000 0.213236000 -0.579186000

132 *

Product A ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP FREQ

%output Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1 6 -12.495437000 0.503756000 2.009390000

6 -12.577256000 -0.339755000 0.779943000

6 -11.423629000 1.239494000 2.315275000

1 -13.203254000 0.229158000 0.072972000

6 -11.263144000 -0.502418000 0.016385000

6 -10.230920000 1.186922000 1.468890000

6 -10.157380000 0.374095000 0.397323000

1 -9.256892000 0.314654000 -0.197254000

1 -13.363478000 0.531486000 2.655241000

8 -11.163580000 -1.295793000 -0.899864000

17 -8.873759000 2.175241000 1.881363000

17 -11.416760000 2.234841000 3.739218000

6 -11.508973000 -2.485798000 2.591873000

6 -12.667371000 -2.629359000 1.963151000

6 -13.304461000 -1.675584000 0.997313000

1 -11.139676000 -3.250828000 3.262271000

1 -10.875337000 -1.617806000 2.463960000

1 -13.242398000 -3.535414000 2.135168000

1 -14.327563000 -1.466024000 1.327992000

1 -13.394355000 -2.166503000 0.024976000 *

133 Product B ! UKS B3LYP D3BJ RIJCOSX def2-TZVP def2/J GRID4 GRID4X TIGHTOP FREQ

%output Print[ P_Basis ] 2 Print[ P_MOs ] 1 end

*xyz 0 1

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140 References

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144 Appendix A

Table A 1: The atomic charges of selected atoms for reactant in the Claisen rearrangement 1a. MPA LPA HPA NPA 1 -0.289381 -0.2046 -0.132672 -0.316982541 2 0.136052 0.130696 0.019792 0.22424746 3 -0.331089 -0.187343 -0.099927 -0.326544357 4 0.140625 0.145447 0.038639 0.239936507 5 -0.268289 -0.239113 -0.080689 -0.374401152 6 0.155637 0.130028 0.027378 0.204525199 7 0.144688 0.127327 0.030045 0.190340173 8 -0.320036 0.119615 -0.147474 -0.347045356

Table A 2: The atomic charges of selected atoms for reactant in the Claisen rearrangement 1b. MPA LPA HPA NPA 1 -0.201014 -0.155747 -0.048462 -0.263337244 2 0.133212 0.135494 0.033318 0.216821901 3 -0.283842 -0.197635 -0.069299 -0.319342398 4 0.138145 0.135999 0.021787 0.22359248 5 -0.264953 -0.235932 -0.050371 -0.344377851 6 0.147109 0.120693 0.027157 0.17537822 7 0.156336 0.12778 0.030888 0.1893368 8 -0.144083 0.079421 -0.05546 -0.045076524

Table A 3: The atomic charges of selected atoms for reactant in the Claisen rearrangement 1c. MPA LPA HPA NPA 1 -0.19818 -0.15075 -0.045385 -0.256936377 2 0.13411 0.13583 0.033991 0.216971065 3 -0.26913 -0.19018 -0.066108 -0.31215777 4 0.14315 0.13598 0.02058 0.223844523 5 -0.26453 -0.23553 -0.050052 -0.343903076 6 0.14738 0.12083 0.027305 0.175501114 7 0.15647 0.12787 0.031007 0.189409377 8 -0.05313 0.0761 -0.356226 0.041583189

145 Table A 4: The atomic charges of selected atoms for reactant in the Claisen rearrangement 1e. MPA LPA HPA NPA 1 -0.21375 -0.16227 -0.055549 -0.268960088 2 0.12507 0.13101 0.029028 0.212227396 3 -0.31168 -0.18832 -0.074839 -0.310937267 4 0.12111 0.12513 0.013058 0.203414533 5 -0.27084 -0.24322 -0.05616 -0.353318215 6 0.15311 0.11881 0.024838 0.173855644 7 0.14292 0.12595 0.028538 0.187742251 8 0.167 0.06762 -0.029676 0.041775044

Table A 5: The atomic charges of selected atoms for reactant in the Claisen rearrangement 1f. MPA LPA HPA NPA 1 -0.3042 -0.20131 -0.070555 -0.327079099 2 0.12476 0.12469 0.021613 0.202113575 3 -0.24593 -0.15673 -0.05793 -0.263451221 4 0.11724 0.12967 0.0256 0.211128394 5 -0.27286 -0.23564 -0.054278 -0.341695501 6 0.13512 0.10609 0.021112 0.163467743 7 0.13554 0.11613 0.03161 0.179866217 8 0.13968 0.05902 0.021886 0.041110692

Table A 6: The atomic charges of selected atoms for reactant in the Claisen rearrangement 1i. MPA LPA HPA NPA 1 -0.183984 -0.13444 -0.035212 -0.242517247 2 0.13724 0.13721 0.036314 0.2175924521 3 -0.27524 -0.15914 -0.057743 -0.2762236466 4 0.15522 0.13961 0.019996 0.2250034294 5 -0.26326 -0.23375 -0.048564 -0.341794242 6 0.14901 0.12793 0.028085 0.1761479576 7 0. 15102 0.12152 0.031596 0.1761479576 8 0.11928 0.13021 -0.087962 0.045672979

Table A 7: The atomic charges of selected atoms for reactant in the Claisen rearrangement 2a. MPA LPA HPA NPA 1 -0.18322 -0.150967 -0.042287 -0.242517247 2 0.13396 0.137333 0.099715 0.216454853 3 -0.294722 -0.175013 -0.059952 -0.28007461 4 0.129059 0.132302 0.016874 0.208878128 5 -0.270277 -0.239688 -0.040392 -0.352150768

146 6 0.143659 0.11944 0.025009 0.174036519 7 0.154661 0.127207 0.029485 0.188558482 8 0.202162 0.075414 0.040603 0.0530312 9 -0.336243 -0.167474 -0.130213 -0.41052784

Table A 8: The atomic charges of selected atoms for reactant in the Claisen rearrangement 2b. MPA LPA HPA NPA 1 -0.206057 -0.158526 -0.045936 -0.254641676 2 0.133405 0.136871 0.034056 0.217629146 3 -0.327144 -0.182349 -0.067538 -0.29374087 4 0.128817 0.132029 0.016072 0.209378266 5 -0.269087 -0.238988 -0.036156 -0.349883482 6 0.144257 0.119602 0.02546 0.174223078 7 0.144257 0.127374 0.030013 0.188942915 8 0.216085 0.056299 0.029549 0.057755106 9 -0.153738 0.069079 -0.9773 -0.059470075

Table A 9: The atomic charges of selected atoms for reactant in the Claisen rearrangement 2c. MPA LPA HPA NPA 1 -0.208294 -0.159834 -0.055732 -0.25914427 2 0.121929 0.130482 0.028917 0.211809317 3 -0.325479 -0.183532 -0.072469 -0.296360504 4 0.120662 0.126351 0.011987 0.203755849 5 -0.271442 -0.242296 -0.038397 -0.354565159 6 0.142333 0.118785 0.024384 0.173625671 7 0.152581 0.125792 0.028312 0.187492298 8 0.174576 0.059741 0.030353 0.037533084 9 0.170778 0.051697 0.009755 0.031807803

Table A 10: The atomic charges of selected atoms for reactant in the Claisen rearrangement 3a. MPA LPA HPA NPA 1 -0.163222 -0.132828 -0.035107 -0.23347266 2 0.404982 0.140089 0.038868 0.220754015 3 -0.264932 -0.177507 -0.058832 -0.290964858 4 0.141248 0.139834 0.025771 0.226825933 5 -0.264714 -0.235204 -0.049614 -0.343598921 6 0.147722 0.120903 0.027379 0.175523119 7 0.157698 0.128442 0.03154 0.190049072 8 -0.102818 0.10609 -0.102337 -0.021075391 9 -0.310274 -0.108604 -0.090837 -0.39335088

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Table A 11: The atomic charges of selected atoms for reactant in the Claisen rearrangement 3b. MPA LPA HPA NPA 1 -0.190109 -0.146018 -0.039825 -0.245901193 2 0.140243 0.141005 0.038219 0.22153495 3 -0.286704 -0.188105 -0.064215 -0.303067641 4 0.140285 0.14165 0.024147 0.227504742 5 -0.263649 -0.233673 -0.048589 -0.341722354 6 0.148295 0.121271 0.027768 0.175733214 7 0.158211 0.128975 0.031933 0.190287631 8 -0.111892 0.076557 0.114262 -0.024090822 9 -0.104469 0.080213 0.116893 -0.017320179

Table A 12: The atomic charges of selected atoms for reactant in the Claisen rearrangement 3c. MPA LPA HPA NPA 1 -0.191213 -0.149441 -0.047678 -0.250017759 2 0.129921 0.134989 0.033414 0.216205495 3 -0.276451 -0.190954 -0.067995 -0.305587262 4 0.133899 0.135352 0.021255 0.223389249 5 -0.265638 -0.237081 -0.051033 -0.345815681 6 0.146602 0.120455 0.026824 0.17522003 7 0.155585 0.127368 0.030394 0.188956097 8 -0.147254 0.079495 -0.453414 -0.052848297 9 0.213974 0.066091 0.016646 0.052587556

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