Copyright 2011, Deepali Butani

PERICYCLIC AND PSEUDOPERICYCLIC: [3, 3] AND [3, 5] REARRANGEMENTS

by

Deepali Butani, M.Sc.

A Dissertation

In

CHEMISTRY

Submitted to the Graduate Faculty

of Texas Tech University in

Partial Fulfillment of

the Requirements for

the Degree of

DOCTOR OF PHILOSOPHY

Approved

David M. Birney, Chairman

Jorge A. Morales

William L. Hase

Peggy Gordon Miller

Dean of the Graduate School

August, 2011

Texas Tech University, Deepali Butani, August 2011

ii

ACKNOWLEDGMENTS

I wish to thank my advisor, Professor David M. Birney, for his excellent

guidance, continued support, freedom and encouragement to pursue interesting and

challenging research problems. His enthusiasm and skill for suggesting efficient

solutions has been a big factor behind most of the work done by me in the last six

years. Even though I was a physical chemist he encouraged me a great deal about

synthetic chemistry and has broadened much of my synthetic point of view.

I would also like to express my sincere thanks to Professor Jorge A. Morales

and Professor William L. Hase for serving in my committee and providing constant

support and advice throughout my doctoral degree.

I am thankful to all the faculty and staff members of the Department of

Chemistry and Biochemistry, Texas Tech University for their support and help during

the period of six years. Their ever-helping nature made my student experience a

memorable one. My sincere thanks to Mr. David W. Purkiss for his help and

assistance with NMR spectroscopy related issues.

I would like to thank Texas Tech University and Robert A Welch Foundation

for the financial support for the research project.

I would like to thank all past and current group members of Dr, Birney’s

group: George Tamas, Shikha Sharma, Trideep Rajale, Jo Ramos, Ali Al-Khafaji,

Krishnaja Duvvuri, Rudhran Mehra, Fabrice Duvernay, Indra Reddy Gudipati, Tina


iii

Thomas, Hua Ji and Sherina Shahbazian who shared their willingness to listen to my

problems, both research and otherwise, and giving useful suggestions and advice.

I have had the fortune of making some great friends during my stay in

Lubbock. Last six years would have been impossible without constant help and

guidance from Arindam Mazumdar and Rahul Kanungoe. They have helped me

completely transforming into a better person. I would also like to thank Cole Seifert

for his unconditional support and helping me learn a lot about life. Also would like to

thank Chandrani Banerjee, Anuja Malvankar, Manav Gupta and Bipasha Deb for their

company during my early years; and Pillhun Son, Eric Clevenger, Sunil Paladugu,

Suresh Pindi and Sekhar Kunapareddy.

At the end, I would like to express my sincere gratitude to all my family

members and relatives for their unconditional support. My cousins, Sajjan Chuggani

and Chandramita Chuggani, Mahesh uncle and Asha aunty have been a constant

source of encouragement for me. I wish to express special gratitude to my father

Pritam Gobindram Butani and my sister, Jaya Butani without whose encouragement

and guidance, I would not have made it here. My mother Late Neena Butani has been

an inspiration to finish my doctoral program. Finally, I would like to dedicate this

thesis to my grandparents, Prem and Pushpa Chawla, who made sure I did something

meaningful in life, and for their love and affection, when it mattered the most.


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TABLE OF CONTENTS

ACKNOWLEDGMENTS ............................................................................................. ii

ABSTRACT ............................................................................................................. vi

LIST OF TABLES .................................................................................................. viii

LIST OF FIGURES ................................................................................................. xiv

I. INTRODUCTION .................................................................................................... 1

1.1 Pericyclic Reactions ..................................................................................... 1

1.2 Pseudopericyclic Reactions .......................................................................... 7

1.3 Sigmatropic Rearrangements ...................................................................... 15

1.4 References ................................................................................................... 23

II. COMPUTATIONAL STUDIES OF SIGMATROPIC REARRANGEMENT OF ALLYLIC

AND VINYLOGOUS AZIDES ................................................................................... 30

2.1 Azide Chemistry ......................................................................................... 30

2.2 Sigmatropic Rearrangement of Allylic Azide ............................................ 35

2.3 Computational Method ............................................................................... 40

2.4 Results and Discussion ............................................................................... 41

2.4.1 Study of [3, 3] Sigmatropic Rearrangement of Allylic Azide ............ 41

2.4.2 Study of [3, 5] Sigmatropic Rearrangement of Vinylogous

(pentadienyl) Azide ........................................................................... 58

2.5 Conclusion .................................................................................................. 73

2.6 References .................................................................................................. 74

III. SYNTHESIS OF PENTADIENYL ALCOHOL DERIVATIVES AND STUDY OF THEIR

POSSIBLE [3, 3] AND [3, 5] SIGMATROPIC REARRANGEMENTS ........................... 82

3.1 Rearrangement of Esters ............................................................................. 82

3.1.1 Background .......................................................................................... 82


v

3.1.2 Computational Study on Rearrangement of Esters .............................. 84

3.1.3 Proposed alcohol molecules ................................................................. 88

3.1.4 Proposed synthesis of phenyl(2-vinylcyclopent-1-enyl)methyl

acetate .................................................................................................. 91

3.1.5 Proposed synthesis of phenyl(2-vinylcyclohex-1-enyl)methyl

acetate .................................................................................................. 95

3.1.6 Flash Vacuum Pyrolysis ....................................................................... 99

3.1.7 Result and Discussion ........................................................................ 103

3.2 Rearrangement of Trichloroacetimidates ................................................... 109

3.2.1 Background ........................................................................................ 109

3.2.2 Proposed synthesis of phenyl(2-vinylcyclopent-1-enyl)methyl 2,2,2-

trichloroacetimidate.............................................................................. 112

3.2.3 Proposed synthesis of phenyl(2-vinylcyclohex-1-enyl)methyl 2,2,2-

trichloroacetimidate ............................................................................ 115

3.2.4. Results and Discussion ....................................................................... 118

3.3 Rearrangement of Xanthates ....................................................................... 119

3.3.1 Background .......................................................................................... 119

3.3.2 Proposed synthesis of S-methyl O-phenyl(2-vinylcyclopent-1-enyl)methyl

carbonodithioate ................................................................................... 121

3.3.3 Proposed synthesis of S-methyl O-phenyl(2-vinylcyclohex-1-enyl)methyl

carbonodithioate ................................................................................... 123

3.3.4. Results and Discussion ......................................................................... 126

3.4 Conclusion .................................................................................................. 127

3.5 Experimental Section ................................................................................... 128

3.6 References .................................................................................................... 155

APPENDICES ........................................................................................................ 161

A. OPTIMIZED CARTESIAN COORDINATES FOR THE

THEORETICAL CALCULATIONS ............................................................. 161

B. 1H-NMR,

13C-NMR, HMQC AND COSY SPECTRA ............................. 196


vi

ABSTRACT

Sigmatropic rearrangements have been known over 100 years. For almost 60

years the [3, 3] sigmatropic rearrangement was known only for the Claisen (one

oxygen present) and the Cope (all carbons) rearrangements, which constituted an

exceptionally versatile class of bond organization processes with many obvious

applications in organic synthesis. More recently, other types of [3, 3] sigmatropic

rearrangements have been studied. Even though [3, 3] sigmatropic rearrangements

have been known for quite a long period of time, there has been very little study done

on [3, 5] sigmatropic rearrangements. In this study, the main aim is to study various

types of reactions undergoing [3, 3] and [3, 5] sigmatropic rearrangements and classify

them as pericyclic or pseudopericyclic.

In the first part of this dissertation, computational studies were carried on allyl

azide and the vinylogous azide to study possible sigmatropic rearrangements of them.

There has been numerous syntheses using [3, 3] rearrangements of allylic azides but

there were not any previous computational studies. Computational studies using

Gaussian 03 at the RB3LYP/6-31G(d,p) level of theory for [3,3] sigmatropic

rearrangements of allylic azides as well as different possible conformers of allyl azide

were calculated. At this level, the activation energy barrier was predicted to be 23.1

kcal/mol and a rate constant of 1.09E-05 s-1

was calculated. Also, as the rearrangement

proceeded through six-centered transition state, the geometry of which suggests that

the reaction is pericyclic in nature. Similar studies were done for the sigmatropic


vii

rearrangement of the vinylogous azide. The vinylogous azide was proposed to have to

two possible thermal pathways, [3, 3] and [3, 5] sigmatropic rearrangements. The

studies clearly showed the formation of eight-centered transition state, with an orbital

disconnection on the azide, indicating it is pseudopericyclic. However, the activation

energy for the [3, 5] rearrangement was calculated to be 42.4 kcal/mol with rate

constant of 7.30E-20 s-1

, which is much higher than the competing [3, 3]

rearrangement, 15.2 kcal/mol.

In the second part of this dissertation, we designed suitable alcohol molecules,

to prepare acetate, trichloroacetimidate and methyl carbonodithioate derivatives, in

such a manner that they could have six- and eight- member transition structures to

possibly see [3, 3] and [3, 5] sigmatropic rearrangements. The reason to synthesize

such molecule was to test the earlier prediction of [3, 3] and [3, 5] rearrangement of

esters. Earlier computational studies done by Birney’s group showed that for a [3, 5]

rearrangement to be allowed the distance between reactive centers need to be close

enough for rearrangement to occur. Preliminary results suggest [3, 3] or [3, 5]

sigmatropic rearrangements can be observed in different molecules.


viii

LIST OF TABLES

2.1 The calculated absolute energies (Hartree), zero-point energies (ZPE, kcal/mol),

relative energies (kcal/mol with respect to ground state), relative energies with

zero-point energy correction (kcal/mol) of different models at different

constrained C-N bond length (Å) at the RB3LYP/6-31G(d,p) level of theory ..... 42

2.2 Dihedral angles (C-C-C-N and C-C-N-N) of ground state, transition state and

different conformers using RB3LYP/6-31G(d,p) level of theory ......................... 44

2.3 The calculated absolute energies (AE, Hartree), dipole moment (DM, Debye), low

or imaginary frequencies (LF, cm-1

), zero-point energies (ZPE, kcal/mol),

absolute energies with zero-point energy correction (AE+ZPE, kcal/mol) and

relative energies with zero-point energy correction (RE, kcal/mol) for the

stationary points of the [3, 3] sigmatropic rearrangement reaction of allyl azide at

the RB3LYP/6-31G(d,p) level of theory ............................................................... 45







the RHF/6-31G(d,p) level of theory ..................................................................... 46





ix




the RMP2/6-31G(d,p) level of theory................................................................... 47

2.6 Calculated thermodynamic data for the [3, 3] sigmatropic rearrangement of allyl

azide at the RB3LYP/6-31G(d,p) level of theory: sum of electronic and thermal

Gibbs free energies (G), sum of electronic and thermal enthalpies (H), and

entropies (S) ........................................................................................................... 48


azide at the RHF/6-31G(d,p) level of theory: sum of electronic and thermal Gibbs

free energies (G), sum of electronic and thermal enthalpies (H), and entropies

(S) .......................................................................................................................... 49


azide at the RMP2/6-31G(d,p) level of theory: sum of electronic and thermal

Gibbs free energies (G), sum of electronic and thermal enthalpies (H), and

entropies (S) ............................................................................................................ 50

2.9 Activation parameters for the [3, 3] sigmatropic rearrangement of allyl azide at

three different level of theory using 6-31G(d.p) basis set using ground state

conformation (1a) as reference. (Gibbs activation free energy, (ΔG≠, kcal/mol),

Enthalpies of activation, (ΔH≠, kcal/mol), Entropy of activation, (ΔS

≠, cal/mol.K),

Activation energy, (Ea, kcal/mol) and Rate constant, (k, s-1

)) ................................ 51


x

2.10 The calculated absolute energies (AE, Hartree), dipole moment (DM, Debye),

low or imaginary frequencies (LF, cm-1


absolute energies with zero-point energy correction (AE+ZPV, kcal/mol) and


stationary points for the [3, 3] sigmatropic rearrangements of cis and trans-1-

azido-2-butene at the RB3LYP/6-31G(d,p) level of theory .................................... 55

2.11 Calculated thermodynamic data for the [3, 3] sigmatropic rearrangements of cis

and trans-1-azido-2-butene at the RB3LYP/6-31G(d,p) level of theory: sum of

electronic and thermal Gibbs free energies (G), sum of electronic and thermal

enthalpies (H), and entropies (S) ............................................................................. 56

2.12 Activation parameters for the [3, 3] sigmatropic rearrangements of trans-1-azido-

2-butene (2) and cis-1-azido-2-butene (4) from 3-azido-1-butene (3) at RB3LYP/6-

31G(d.p) level of theory using thermodynamic parameters from Table 2.11. (Gibbs

activation free energy, (ΔG≠, kcal/mol), Enthalpies of activation, (ΔH

≠, kcal/mol),

Entropy of activation, (ΔS≠, cal/mol.K), Activation energy, (Ea, kcal/mol) and Rate

constant, (k, s-1

)) ...................................................................................................... 56







xi

stationary points of the [3, 5] and [3, 3] sigmatropic rearrangements of the

vinylogous azide at the RB3LYP/6-31G(d,p) level of theory ................................ 62







vinylogous azide at the RHF/6- 31G(d,p) level of theory ....................................... 63







vinylogous azide at the RMP2/6-31G(d,p) level of theory ..................................... 64

2.16 Calculated thermodynamic data for the [3, 5] and [3, 3] sigmatropic

rearrangements of the vinylogous azide at the RB3LYP/6-31G(d,p) level of theory:

sum of electronic and thermal Gibbs free energies (G), sum of electronic and

thermal enthalpies (H), and entropies (S) ............................................................... 65


rearrangements of the vinylogous azide at the RHF/6-31G(d,p) level of theory:


xii




rearrangements of the vinylogous azide at the RMP2/6-31G(d,p) level of theory:



2.19 Activation parameters for the [3, 5] and [3, 3] sigmatropic rearrangements of

vinylogous azide 16 and 19 from 15 at three different levels of theory using 6-

31G(d,p) basis set. (Gibbs activation free energy, (ΔG≠, kcal/mol), Enthalpies of

activation, (ΔH≠, kcal/mol), Entropy of activation, (ΔS

≠, cal/mol.K), Activation

energy, (Ea, kcal/mol) and Rate constant, (k, s-1

)) .................................................. 69

2.20 Dihedral angles of various structures of vinylogous azide rearrangements using

RB3LYP/6-31G(d,p) level of theory....................................................................... 70

3.1 Calculated strain energy, total energy and potential energy of minimized structure

of a series of pentadienyl alcohols using MM2 ............................................................ 89

3.2 Calculated strain energy, total energy and potential energy of minimized structures

of various possible acetates and their possible [3, 3] and [3, 5] rearranged products

using MM2 .................................................................................................................... 91


of various possible acetates and their possible [3, 3] and [3, 5] rearranged products

using MM2 .................................................................................................................... 96


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3.4 Flash Vacuum Pyrolysis (FVP) experimental setup ............................................. 102

3.5 Products formed on pyrolysis of phenyl(2-vinylcyclopent-1-enyl)methyl acetate

(25) at two different temperatures ............................................................................... 104

3.6 Products formed on pyrolysis of phenyl (2-vinylcyclohex-1-enyl) methyl acetate

(33) at three different temperatures ............................................................................. 107


of trichloroacetimidate, 41 and their possible [3, 3], (42) and [3, 5], (43) rearranged

products using MM2 ................................................................................................... 114


of trichloroacetimidate, 44 and their possible [3, 3], (45) and [3, 5], (46)

rearrangement products using MM2 ........................................................................... 117


of xanthate, 47 and its possible [3, 3] (48) and [3, 5] (49) rearrangement products

using MM2 .................................................................................................................. 122

3.10 Calculated strain energy, total energy and potential energy of minimized

structures of xanthate, 50 and its possible [3, 3], (51) and [3, 5], (52) rearrangement

products using MM2 ................................................................................................... 125


xiv

LIST OF FIGURES

1.1 Complete orbital symmetry correlation diagram for the formation of cyclobutane

from two molecules of ethylene ................................................................................ 2

1.2 Orbital symmetry correlation diagram for the allowed conrotatory ring opening of

3,4-dimethylcyclobutene. .......................................................................................... 3

1.3 Orbital correlation diagram for the allowed disrotatory ring opening of 5,6-

dimethylcyclohexa-1,3-diene .................................................................................... 4

1.4 [3, 3] Sigmatropic rearrangement of octa-2,6-diene ................................................. 5

1.5 Example of Group Transfer reaction between an alkene and enophile .................... 5

1.6 (a) Addition of sulfur dioxide to butadiene; (b) Thermal cheletropic

decarbonylation of 3-cyclopentenone ....................................................................... 6

1.7 Dyotropic reactions (a) Type 1 reaction (b) Type 2 reaction .................................... 7

1.8 Degenerate rearrangement of PFDTSO .................................................................... 8

1.9 Proposed pseudopericyclic orbital interaction in the rearrangement of PFDTSO .... 8

1.10 Prototropy in internally hydrogen bonded enols of β-dicarbonyl compounds ........ 9

1.11 Orbitals and their interactions in the pseudopericyclic reaction of the addition of

the water to formylketene........................................................................................ 11

1.12 Orbital interactions in the pseudopericyclic decarbonylation of transition state of

furandione ............................................................................................................... 12

1.13 Examples of low or no barrier for pseudopericyclic reactions. ............................ 14

1.14 [1, 3] shift in the bicyclo[3.2.0] hept-ene system .................................................. 16


xv

1.15 Possible pathways for concerted [1, 3] migration ................................................. 17

1.16 Antara-antara [1, 5] methylene sigmatropic shift in propenylidene

cyclopropane ........................................................................................................... 18

1.17 1, 7] sigmatropic rearrangement of in o-butadienylphenols where it has one

orbital disconnection ............................................................................................... 19

1.18 General mechanism of [2, 3]-sigmatropic rearrangement..................................... 19

1.19 [2, 3]-sigmatropic rearrangement of benzyl allyl ether ......................................... 20

1.20 (a) Claisen and Cope rearrangements, (b) Transition state of the [3, 3] Claisen

rearrangement showing effects of stereochemistry, (c) Transition state of the [3, 3]

Cope rearrangement showing effects of stereochemistry ....................................... 21

1.21 [5, 5] shift of phenyl pentadienyl ether ................................................................. 22

2.1 Representative resonance structures of azides ........................................................ 31

2.2 Products from unimolecular decomposition of azides ............................................ 32

2.3 Nitrene products from azides .................................................................................. 32

2.4 Rearrangement products from azides ...................................................................... 32

2.5 Zwittazido cleavage of azides (a) general mechanisms, (b) a specific example ..... 33

2.6 Mechanism of acid-catalyzed decomposition ......................................................... 34

2.7 Mechanism of Staudinger Reaction ........................................................................ 34

2.8 Mechanism of Curtius Rearrangement.................................................................... 34


xvi

2.9 Reaction of Schmidt Rearrangement ...................................................................... 34

2.10 Reaction showing reduction .................................................................................. 35

2.11 Reaction showing Cycloaddition .......................................................................... 35

2.12 Mechanism showing nucleophilic attack at the azide terminus ............................ 35

2.13 [3, 3] Sigmatropic rearrangement of allyl azide (1) .............................................. 36

2.14 Rearrangement of an allylic azide ......................................................................... 37

2.15 Concerted rearrangement vs. SN2ʹ attack. Top: the expected SN2 pathway of

nucleophilic opening of epoxide, 1; middle: allylic azide rearrangement of 2

leading to 4-azido-2-buten-1-ol, 3; bottom: alternative SN2ʹ pathway leading to 4-

azido-2-buten-1-ol, 2 ............................................................................................... 38

2.16 Equilibrium between α- and γ-methylallyl azide .................................................. 38

2.17 Possible mechanistic alternatives for the allylic rearrangement ........................... 39

2.18 (a) [3, 3] Sigmatropic Rearrangement of allylic azide (1); (b) Molecular orbital

diagram of azide ...................................................................................................... 41

2.19 Energy profile showing relative energy and constrained C-N bond distance. This

helps in determining which structure should be taken to optimize at ground state

and transition state................................................................................................... 43

2.20 IRC calculation of transition state of the allylic azide using the RB3LYP/6-

31G(d,p) level of theory .......................................................................................... 44


xvii

2.21 Energy profile (RE from Table 2.3) of the [3,3] sigmatropic rearrangement of the

allyl azide and different conformers of the allyl azide at B3LYP/6-31G(d,p) level

of theory, where GS stands for ground state (1a), TS for transition state (5), C1 for

conformation1 (1b), C2 for conformation-2 (1c), C3 for conformation-3 (1d) and

C4 for conformation-4 (1e). Their relative energies in kcal/mol with respect to

ground state are provided in parentheses ................................................................ 52

2.22 Three different views of the transition state of the [3, 3] sigmatropic

rearrangement of allyl azide. Bond Lengths: C(6)-N(1) = 2.07 Å, C(4)-N(3) = 2.07

Å; Bond Angles: N(1)-N(2)-N(3) = 163.13°, C(4)-C(5)-C(6) = 120.39° ............... 53

2.23 Energy profile (RE from Table 2.11) for the [3, 3] sigmatropic rearrangements of

cis and trans-1-azido-2-butene at the RB3LYP/6-31G(d,p) level of theory, where

trans-1-azido-2-butene (2), 3-azido-1-butene (3), cis-1-azido-2-butene (4), trans-

transition state (6) and cis-transition state (7). Their relative energies in kcal/mol

with respect to 2 are provided in parentheses ......................................................... 57

2.24 Structure of trans-transition state (6). Bond Lengths: C(6)-N(1) = 2.11 Å, C(4)-

N(3) = 2.13 Å; Bond Angles: N(1)-N(2)-N(3) = 164.6°, C(4)-C(5)-C(6) = 121.3°,

C(5)-C(6)-C(7) = 123.1°, N(1)-C(6)-C(7) = 153.6° ............................................... 57

2.25 Structure of cis-transition state (7). Bond Lengths: C(6)-N(1) = 2.13 Å, C(4)-N(3)

= 2.11 Å; Bond Angles: N(1)-N(2)-N(3) = 164.5°, C(4)-C(5)-C(6) = 122.9°, C(5)-

C(6)-C(7) = 125.2°, N(1)-C(6)-C(7) = 97.0° .......................................................... 58

2.26 The [3,3] and [3,5] sigmatropic rearrangement of vinylogous azide (8) .............. 59


xviii

2.27 IRC run for transition state-1 (11): (a) IRC run in forward direction towards

possible product and (b) IRC run in reverse direction towards possible reactant

using RB3LYP/6-31G(d,p) level of theory. ............................................................ 60

2.28 IRC calculations for transition state-2 (14): (a) IRC calculations in reverse

direction towards possible reactant and (b) IRC calculations in forward direction

towards possible product using RB3LYP/6-31G(d,p) level of theory .................... 61

2.29 Energy profile (RE from Table 2.13) for the [3, 5] and [3, 3] sigmatropic

rearrangements of vinylogous azide at the RB3LYP/6-31G(d,p) level of theory.

Their relative energies in kcal/mol with respect to 16 are provided in

parentheses .............................................................................................................. 68

2.30 Three different views of 11 using RB3LYP/6-31G(d,p) level of theory. Bond

Lengths: N(1)-C(8) = 1.69 Å, N(3)-C(4) = 1.48 Å; Bond Angles: N(1)-N(2)-N(3)

= 140.8°, N(2)-N(3)-C(4) = 121.7°, N(3)-C(4)-C(5) = 109.7°, C(6)-C(7)-C(8) =

129.3°; Dihedral angle: C(8)-N(1)-N(3)-C(4) = 25.7° ............................................ 71



= 174.2°, C(4)-C(5)-C(6) = 128.4°, C(6)-C(7)-C(8) = 126.2°; Dihedral angle:

C(8)-N(1)-N(3)-C(4) = -59.4° ................................................................................. 71




xix

= 123.1°, N(2)-N(3)-C(4) = 101.9° C(4)-C(5)-C(6) = 61.4°, C(6)-C(7)-C(8) =

126.1°; Dihedral angle: C(8)-N(1)-N(3)-C(4) = -53.1° .......................................... 72



= 167.9°, N(2)-N(3)-C(4) = 93.9° C(4)-C(5)-C(6) = 122.1°, C(6)-C(7)-C(8) =

123.4°. Dihedral angle: C(6)-N(1)-N(3)-C(4) = -6.82° .......................................... 72

3.1 Energy profile showing the [3, 3] rearrangement of 2,4-cyclohexadienyl formate,

10 to 11 (right side) and the degenerate [3, 5] rearrangement of 2,4-

cyclohexadienyl formate, 10 (left side), with their transition states (10ǂ and 11

ǂ) in

between. The geometries were calculated at the MP2/6-31G** level of theory and

the relative energies were calculated at the MP4/6-31G** + ZPV (kcal/mol) level

of theory. ................................................................................................................. 86

3.2 Energy profile showing 12 forming a boat transition state leading to the [3, 3]

rearrangement of 13. The relative energies in kcal/mol were calculated at the

MP4/6-31G** level of theory ................................................................................. 87

3.3 MM2 minimized structure of phenyl(2-vinylcyclohex-1-enyl)methanol (16, side

viewed from two different directions) where blue are H-atoms, grey are carbon

atoms, red are oxygen atoms and pink are lone pair orbitals .................................. 90

3.4 MM2 minimized structure of phenyl(2-vinylcyclopent-1-enyl)methanol (18, side

viewed from two different directions) where blue are H-atoms, grey are carbon

atoms, red are oxygen atoms and pink are lone pair orbitals .................................. 90


xx

3.5 MM2 minimized structure of phenyl(2-vinylcyclopent-1-enyl)methyl acetate (25)

where blue are H-atoms, grey are carbon atoms, red are oxygen atoms and pink are

lone pair orbitals ...................................................................................................... 94

3.6 MM2 minimized structure of [3, 3] (26) and [3, 5] (27) rearrangement products

from phenyl(2-vinylcyclopent-1-enyl)methyl acetate (25); where blue are H-

atoms, grey are carbon atoms, red are oxygen atoms and pink are lone pair

orbitals ...................................................................................................................... 94

3.7 MM2 minimized structure of phenyl(2-vinylcyclohex-1-enyl)methyl acetate (33)

where blue are H-atoms, grey are carbon atoms, red are oxygen atoms and pink are

lone pair orbitals ...................................................................................................... 98

3.8 MM2 minimized structure of [3, 3], 34 and [3, 5], 35 rearrangement products from

phenyl(2-vinylcyclohex-1-enyl)methyl acetate (33); where blue are H-atoms, grey

are carbon atoms, red are oxygen atoms and pink are lone pair orbitals ................ 98

3.9 Flash Vacuum Pyrolysis (FVP) setup ................................................................... 102

3.10 1H-NMR from FVP of 25, obtained column chromatography where boxed signals

are possibly from [3, 5] rearrangement ................................................................. 105

3.11 1H-NMR from FVP of 33, obtained column chromatography where boxed

signals are possibly from [3, 5] rearrangement ................................................... 108

3.12 Cyclic six-centered transition state of the [3, 3] rearrangement of allylic imidates

where R, R1, R2, R3, R4 are various alkyl groups ................................................ 111


xxi

3.13 MM2 minimized structure of phenyl(2-vinylcyclopent-1-enyl)methyl 2,2,2-

trichloroacetimidate (41) where blue are N-atom, grey are C- atoms, red are O-

atom, pink are lone pair orbitals, green are Cl-atoms and white are H-atoms .... 113

3.14 MM2 minimized structure of phenyl(2-vinylcyclohex-1-enyl)methyl 2,2,2-

trichloroacetimidate (44) where blue are N-atom, grey are C- atoms, red are O-

atom, pink are lone pair orbitals, green are Cl-atoms and white are H-atoms .... 116

3.15 Energy profile showing the [3, 3] sigmatropic rearrangement of allylic xanthates

calculated at the MINDO/3 level of theory ......................................................... 120

3.16 Minimized structure of S-methyl O-phenyl (2-vinylcyclopent-1-enyl) methyl

carbonodithioate (47) where yellow are S-atom, grey are C- atoms, red are O-

atom, pink are lone pair orbitals, and white are H-atoms using MM2 ................ 121

3.17 Minimized structure of S-methyl O-phenyl(2-vinylcyclohex-1-enyl)methyl

carbonodithioate (50) where yellow are S-atom, grey are C- atoms, red are O-

atom, pink are lone pair orbitals, and white are H-atoms using MM2 level of

theory ................................................................................................................... 124


1

CHAPTER I

INTRODUCTION

1.1 PERICYCLIC REACTIONS

Pericyclic reactions represent an important class of concerted (single step)

processes involving σ- and π- systems. The fact that the reactions are concerted often

gives good stereochemical control of the product. By definition, pericyclic reactions

have a cyclic transition state. In the transition state, a concerted rearrangement of the

electrons takes place which causes σ- and π-bonds to simultaneously break and form.

Pericyclic reactivity can be understood in terms of frontier molecular orbital (FMO)

theory1 which can be explained by the favorable overlap of the Highest Occupied

Molecular Orbital (HOMO) and the Lowest Unoccupied Molecular Orbital (LUMO)

in the transition states. Alternatively, the outcome of reactions can be predicted by

considering the conservation of orbital symmetry. The conclusion of these analysis on

a variety of reactions are summarized in the Woodward-Hoffmann rules.2 These

reactions are popular with synthetic chemists because the reagents and conditions are

mild and the reactions are very “clean” unlike many organic chemical reactions that

results in the formation of large quantities of brown-black, smelly by-product of

unknown composition. Woodward and Hoffmann defined pericyclic reactions as ones

in which all the first order changes in bonding relationships take place in a concerted

closed curve.2 The following are six common types of pericyclic reactions. These


2

reactions can either be induced to occur under thermal conditions with simple heating

or under photochemical conditions.3,4,5

1. Cycloaddition: A cycloaddition is a pericyclic chemical reaction, in

which "two or more unsaturated molecules (or parts of the same molecule)

combine with the formation of a cyclic adduct in which there is a net

reduction of the bond multiplicity."6,7

Cycloaddition reactions can be

suprafacial / suprafacial (SS) or suprafacial/ antarafacial (AS). The orbital

correlation diagram for cycloaddition of two ethylene molecules to form

cyclobutane is shown in Figure 1.1 as a four-electron system, it is

thermally forbidden but photochemically allowed.

Figure 1.1: Complete orbital symmetry correlation diagram for the formation of

cyclobutane from two molecules of ethylene.2


3

2. Electrocyclic Reaction: An electrocyclic reaction is a type of pericyclic

rearrangement reaction where the net result is one π-bond being converted

into one σ- bond or vice-versa.7,8

The stereospecificity of the

rearrangement is determined by conrotatory or disrotatory mode of

transition state formation as predicted by the Woodward-Hoffmann rules.

The correlation diagram in Figure 1.2 shows how only a conrotatory ring

opening of 3,4-dimethylcyclobutene is symmetry allowed whereas the

correlation diagram in Figure 1.3 shows how only a disrotatory ring

opening of 5,6-dimethylcyclohexa-1,3-diene is symmetry allowed. This is

because only in these cases would maximum orbital overlap occur in the

transition state. Also, the product would be formed in the ground state

rather than an excited state.

Figure 1.2: Orbital symmetry correlation diagram for the allowed

conrotatory ring opening of 3,4-dimethylcyclobutene.9


4

Figure 1.3: Orbital correlation diagram for the allowed disrotatory ring

opening of 5,6-dimethylcyclohexa-1,3-diene.9

3. Sigmatropic Rearrangement: The sigmatropic rearrangement is a

pericyclic reaction wherein the net result is one σ-bond is changed to

another σ-bond in an uncatalyzed intramolecular process.10

In this type of

rearrangement reaction, a substituent moves from one part of a π-bonded

system to another part in an intramolecular reaction with simultaneous

rearrangement of the π system. In sigmatropic rearrangements the


5

transition state can be visualized as an association of two fragments

connected at their termini by two partial σ-bonds, one being broken and the

other being formed. Considering only atoms within the (real or

hypothetical) cyclic array undergoing reorganization, if the numbers of

these in the two fragments are designated i and j, then the rearrangement is

said to be a sigmatropic change of order [i, j] (conventionally [ i ] ≤ [ j ]).7

Figure 1.4 is an example showing the sigmatropic rearrangement of two

allyl fragments.11

Figure 1.4: [3, 3] Sigmatropic rearrangement of octa-2,6-diene.11

4. Group Transfer Reactions: Group transfer reactions are type of pericyclic

reactions where one π-bond is converted into one σ-bond, with migration

of σ- bond.12

Figure 1.5: Example of Group Transfer reaction between an alkene and

enophile. 12


6

5. Cheletropic reactions: Cheletropic reactions are pericyclic reactions which

involve formation of a transition state with a cyclic array of atoms and an

associated cyclic array of interacting orbitals. In other words, it is a

reorganization of σ and π bonds in a cyclic array.3

(a)

(b)

Figure 1.6: (a) Addition of sulfur dioxide to butadiene.3

(b) Thermal cheletropic decarbonylation of 3-cyclopentenone.88

6. Dyotropic reactions: A dyotropic reaction is a type of organic reaction and

more specifically a pericyclic valence isomerization in which two sigma

bonds simultaneously migrate intramolecularly.13

They can be either Type I

in which two migrating groups interchange their positions or Type II which

involves migration of new bonding sites without change of position (Figure

1.7)


7

Figure 1.7: Dyotropic reactions (a) Type 1 reaction (b) Type 2 reaction.13

1.2 PSEUDOPERICYCLIC REACTIONS

In 1976, Lemal and coworkers

14 were first to propose the name

“pseudopericyclic”. They proposed this name because they saw an extraordinarily

facile sigmatropic rearrangement for automerization while studying

perfluorotetramethyl Dewar thiophene exo-S-oxide (PFDTSO) by NMR at low

temperatures as shown in Figure 1.8. They found one signal at –100 °C (which could

be interpreted as structure c in Figure 1.8). Below –100 °C, the signal split into two,

corresponding to structure a (Figure 1.8). This led them to suggest that a rapid

exchange between the sulfoxide moiety and the rest of the molecule was taking place

in a degenerate rearrangement .


8

Figure 1.8: Degenerate rearrangement of PFDTSO.14

Since 1, 3-sigmatropic rearrangements of hydrocarbons are symmetry

forbidden, Lemal and coworkers

14 proposed what they termed a pseudopericyclic

mechanism. They suggested that the low activation energy (of exchange at -124 °C

was 6.8 ± 0.3 kcal/mol) of the reaction was due to a sulfur lone pair (i.e. nonbonding

orbital) forming a new bond to carbon, while the electrons from the cleavage of C-S

bond (i.e. orthogonal orbital) becoming a new lone pair as shown in Figure 1.9.14

This

avoided the cyclic orbital overlap of a pericyclic rearrangement.

Figure 1.9: Proposed pseudopericyclic orbital interaction in the rearrangement of

PFDTSO.14

Hence, Lemal14

defined the term “pseudopericyclic reactions” as a concerted

transformation whose primary changes in bonding compassed a cyclic array of atoms,


9

at one (or more) of which nonbonding and bonding atomic orbitals interchange roles.

In the crucial sense the role interchange meant that there was a “disconnection” in the

cyclic array of overlapping orbitals because the atomic orbitals switching functions

were mutually orthogonal. This means that pseudopericyclic reactions cannot be

orbital symmetry forbidden.

Prototropy in internally hydrogen bonded enols of β-dicarbonyl compounds

(Figure 1.10) is an example of pseudopericyclic reaction.15

As the proton tunnels

between minima, lone pair and bonding orbitals formally interchange functions at

both oxygens in the planar chelate ring. Basically, a bonding p orbital and a

nonbonding lone pair orbital switches roles at left-hand oxygen, while a

complementary interchange occurs at the oxygen on the right. Although the

bonding/nonbonding distinction was not absolute, the separation of this concerted

process into persistently orthogonal σ and π components proved the fact that it was

not pericyclic.15

Figure 1.10: Prototropy in internally hydrogen bonded enols of β-dicarbonyl

compounds.15

Nearly 20 years later Birney and coworkers16

began a systematic study of a

series of pseudopericyclic reactions based on quantitative theory, transition state

calculations and experiments on a variety of thermal pseudopericyclic reactions,


10

including cycloadditions,17,20,21,38-42

sigmatropic rearrangements,18,40,43,44

electrocyclizations,17-19

cheletropic fragmentations,16,45

and group

transfers/eliminations.46

Based on these studies, a series of generalizations have been

developed. These are summarized as the following16-24

:

1. A pseudopericyclic reaction may be orbital symmetry allowed via a

pathway that maintains the orbital disconnections, regardless of the

number of electrons involved.

In pericyclic reactions aromatic orbitals overlap to form a

cyclic system and this is implicit in the pattern of alternating

allowed and forbidden predictions by Woodward-Hoffmann rules

and Frontier Molecular Orbital theory. These theories are useful but

are not directly applicable to pseudopericyclic reactions. In

pseudopericyclic reactions there are two kinds of orbital

interactions: in-plane orbital overlaps and out-of-plane ones. Since

these orbital interactions lead to disconnections between orbitals of

reactants, counting electrons to predict whether the reaction is

allowed becomes irrelevant. Examples illustrating the disconnection

of orbitals are:


11

Orbital topology is the [4 + 2] cycloaddition of water to

formylketene as shown in Figure 1.11.

Figure 1.11: Orbitals and their interactions in the pseudopericyclic

reaction of the addition of the water to formylketene.17

For the decarbonylation of furandione (Figure 1.12) a

pseudopericyclic orbital topology is possible, with two orbital

disconnections, i.e. two atoms where orthogonal sets of orbitals meet,

but do not overlap. Because no electrons are exchanged between the in-

plane and out-of-plane orbitals, the transition state for decarbonylation

of furandione is orbital symmetry allowed when the CO departs in the

plane of the molecule.


12

Figure 1.12: Orbital interactions in the pseudopericyclic

decarbonylation of transition state of furandione.16

2. Barriers to pseudopericyclic reactions can be very low or even

nonexistent

(a) If there is a good match between nucleophilic and

electrophilic sites in reactants

(b) If the geometrical constraints of the system allow for

appropriate angles in transition state, in close analogy to

Baldwin’s rules.35

(c) If the reaction is exothermic.


13

Pericyclic reactions are often easy to perform due to maximum

bonding orbital overlap arising in the concerted allowed pathway.

But the barrier for activation energy is roughly between 20-30

kcal/mol,47,48

which is substantially high. It is because pericyclic

reactions involve the unavoidable electron-electron repulsion

between interacting orbitals from the aromatic of transition states.49

Whereas, in case of pseudopericyclic reactions, there can be very

low or sometimes no barrier. This is because there is a lack of

cyclic orbital overlap which avoids electron-electron repulsion. In

addition, the planar transition state allows for a better orbital

overlap. For instance, in the addition of water to formylketene the

low barrier of 6.3 kcal/mol, because the lone pair of electrons on

oxygen in water attacks the carbon of ketene in plane and hence

there is no overlap of the out-of-plane p orbitals. The reaction also

has a match between the nucleophilic site of lone pairs on oxygen

of water and the electrophilic site of carbonyl carbon on ketene and

also the nucleophilic oxygen on ketene and electrophilic hydrogen

on water. As the lone pair on oxygen attacks the carbonyl carbon

the negative charge is dispersed to oxygen on ketene. This results in

an increased nucleophilicity of the oxygen, which ultimately helps

in abstracting the hydrogen from water easily. As there is no

accumulation of charge and also the electron-electron repulsion is


14

minimal, these have lower energy barriers. More examples of low

barrier pseudopericyclic reactions are shown in Figure 1.13.48

Figure 1.13: Examples of low or no barrier for pseudopericyclic

reactions.48

3. Pseudopericyclic reactions have a planar transition states if possible.

However, crowding at transition states can lead to small distortions

from planarity. This is in contrast to typically all hydrocarbon

pseudopericyclic reactions for which the need to maintain orbital

overlap leads to non-planar transition states.36,37

In pericyclic reactions it is essential that orbitals are non-planar so as to

maximize their overlap in the transition state. In contrast, for pseudopericyclic

reactions there is no or little overlap between out of plane (π) and in-plane (σ and π)

orbitals.

Birney16-24,50

and several other authors25-34

have been working in field of

pseudopericyclic for several years to show that a number of organic syntheses involve


15

this type of process. However, until now there is no universally accepted clear-cut,

absolute criterion for distinguishing a pseudopericyclic reaction from a normal

pericyclic reaction.

Pericyclic and pseudopericyclic reactions can be distinguished from each other using

several methods:

1. Density Functional Theory (DFT) and many other computational methods

are used to determine the barrier of reaction and also the pathway of

reaction. Often the geometry of the transition state requires an orbital

disconnection.

2. The study of magnetic properties and their relation with aromaticity. As

pericyclic reactions proceed via an aromatic transition state whereas in

pseudopericyclic arrangement aromaticity is avoided at transition state.

Two commonly used methods are Nucleus Independent Chemical Shift

(NCIS)51,52

and Anisotrop of Chemical-Induced Density (ACID).53,54

3. Pseudopericyclic reactions can occur regardless of the number of atoms

involved. Therefore observing both a six-centered and an eight-centered

reaction would suggest both are pseudopericyclic.

1.3 SIGMATROPIC REARRANGEMENTS

Sigmatropic reactions55,56

of neutral molecules are of special interest, as they are

controlled by the conservation of orbital symmetry.3 These reactions involve

intramolecular migration of a group from one carbon to another, and an obvious


16

experiment is to compare the migratory aptitudes of various groups in these reactions

with those found in other rearrangements. The purposes of such a comparison are to

provide predictive power over the facility of sigmatropic reactions and to gain a more

detailed knowledge of the transition-state structure for group migrations. Thermal and

photochemical [i, j] sigmatropic rearrangement can occur either via suprafacial or

antarafacial pathways, and the resultant product has stereochemical consequences.57-60

Classes of Sigmatropic Rearrangement are:

1. [1, 3] shift: A [1, 3] shift involves the shift of one atom (or substituent, -H

or -R) down three atoms of a π system. The Woodward-Hoffmann rules

dictate that a thermal [1, 3] shift would proceed via an antarafacial shift.

Although such a shift is symmetry allowed, the Mobius topology required

in the transition state prohibits such a shift because it is geometrically

impossible. Berson and Nelson have described an example of [1,3] shift in

the bicyclo[3.2.0] hept-ene system (Figure 1.14) demonstrating that

inversion does occur for the suprafacial path but with a high barrier,

presumably because the reaction is forbidden.61,62

Figure 1.14: [1, 3] shift in the bicyclo[3.2.0] hept-ene system.61,62


17

If the migrating atom is capable of undergoing stereochemical

inversion, then the selection rules allow two distinct suprafacial or

antarafacial routes with attendant retention or inversion at the migrating

center (Figure 1.15).62

Figure 1.15: Possible pathways for concerted [1, 3] migration.62

2. [1, 5] shift: A [1, 5] shift involves the shift of 1 substituent (-H, -R or -Ar)

down 5 atoms of a π system.63

The methylene sigmatropic shift in

propenylidene cyclopropane (Figure 1.16) occurs by Antara-Antara [1,5]

methylene shift and is pericyclic in nature but if heteroatoms like N and O


18

are introduced at both reacting termini of parent molecule then they can

become pseudopericyclic in nature.64

Figure 1.16: Antara-antara [1, 5] methylene sigmatropic shift in

propenylidene cyclopropane.64

3. [1, 7] shift: Thermal [1, 7] sigmatropic shifts are predicted by the

Woodward-Hoffmann rules to proceed in an antarafacial fashion, via a

Möbius topology transition state. The 4n-π-electron series explores the

competition between the antarafacial mode being manifested via inversion

at a single carbon, or antarafacial along a chain of atoms. Thus a [1, 7]

hydrogen shift can only occur antarafacially.65,66

Migration of hydrogen from oxygen to carbon in o-butadienylphenols

(Figure 17) 67,68

involves a [1, 7] shift. The [1, 7] shift is also responsible

for cis-trans isomerism 2, and competes favorably with electrocyclic ring

closure to 3.


19

Figure 1.17: [1, 7] sigmatropic rearrangement of in o-butadienylphenols where

it has one orbital disconnection.67,68

4. [2, 3] shift: The general scheme of [2, 3] sigmatropic rearrangement is

shown in Figure 1.18.

Figure 1.18: General mechanism of [2, 3]-sigmatropic rearrangement.75

Atom Y in Figure 1.18 can be oxygen, sulfur, selenium, or nitrogen. If Y is

nitrogen, the reaction is referred to as a 2, 3-Stevens rearrangement; if Y is

oxygen, then it is called a 2, 3-Wittig rearrangement. Because the reaction

is concerted, it exhibits a high degree of stereocontrol, and can be

employed early in a synthetic route to establish stereochemistry. The Wittig

rearrangement requires strongly basic conditions, however, as a carbanion

intermediate is essential.69-74

[2, 3] sigmatropic rearrangement is defined as

a thermal isomerization that proceeds via a six-electron, five-membered

cyclic transition state. [2, 3]-sigmatropic rearrangement of benzyl allyl

ether (as shown in Figure 1.19)75

where the new bond formed has a 2,3-

relationship to the old and the transition state is a five-membered ring. The


20

transition state can be quite chair-like so that the new π bond will be trans

if it has a choice.

Figure 1.19: [2, 3]-sigmatropic rearrangement of benzyl allyl ether.75

5. [3, 3] shift: [3, 3] sigmatropic rearrangements76-79

are the one which

follow the Woodward-Hoffmann rules predicting that the reaction proceeds

suprafacially with six electrons and it forms a Hückel topology transition

state. The [3, 3] sigmatropic processes are characterized by the formation

of highly ordered transition states where repulsive interactions are

minimized. The Claisen80-83

and the Cope84-86

rearrangement are known as

reliable protocols to generate defined configured tertiary and quaternary

carbon centers as well as complicated C atom-heteroatom bonds. The [3,

3] rearrangement defines the product olefin geometry. Also, the

stereospecific bond reorganization of the reactant helps in the prediction of

stereogenic properties of the product as shown in Figure 1.20 (a, b and c).


21

Figure 1.20: (a) Claisen and Cope rearrangements. (b) Transition state of the [3,

3] Claisen rearrangement showing effects of stereochemistry. (c) Transition state

of the [3, 3] Cope rearrangement showing effects of stereochemistry.


22

6. [5, 5] shift: [5, 5] Sigmatropic shifts also proceed suprafacially by Hückel

topology transition state. An example of such a rearrangement is the [5, 5]

shift is seen in rearrangement of phenyl pentadienyl ether (Figure 1.21).89

Figure 1.21: [5, 5] shift of phenyl pentadienyl ether.89

There are different classes of sigmatropic rearrangements classified and most

of them are pericyclic in nature. Our aim throughout this dissertation will be study

potential [3, 5] sigmatropic rearrangements which we expect will pseudopericyclic in

nature.


23

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73. Vogel, C. Synthesis 1997, 497.


28

74. (a) Hoffmann, R. W. Angew. Chem., Int. Ed. Engl. 1979, 18, 563. (b)

Hiersemann, M.; Abraham, L.; Pollex, A. Org. Biomol. Chem. 2003,

1, 1088.

75. McNally, A.; Evans, B.; Gaunt, M. J. Angew. Chem. Int. Ed. 2006, 45,

2116-2119.

76. Hansen, H. J.; Schmid, H. Tetrahedron 1974, 30, 1959.

77. Andreev, V. G.; Kolomiets, A. F. Russ. Chem. Rev. 1993, 62, 553.

78. Enders, D.; Knopp, M.; Schiffers, R. Tetrahedron: Asymmetry 1996,

7, 1847.

79. Nubbemeyer, U. Synlett. 2003, 961.

80. Castro, A. M. M. Chem. Rev. 2004, 104, 2939.

81. Claisen, L.; Ber. 1912, 45, 3157.

82. Claisen, L.; Tietze, E.; Ber. 1925, 58, 275.

83. Claisen, L.; Tietze, E.; Ber. 1926, 59, 2344.

84. Cope, A. C.; Hardy, E. M. J. Am. Chem. Soc. 1940, 62, 441.

85. Hoffmann, R.; Stohrer, W. D. J. Am. Chem. Soc. 1971, 93, 6941.

86. Dupuis, M.; Murray, C.; Davidson, E. R. J. Am. Chem. Soc. 1991, 113,

9756.

87. Klarner, F.G. Topics in Stereochem. 1984, 15, 1.

88. Unruh, G. R.; Birney, D. M., J. Am. Chem. Soc. 2003, 125, 8529 –

8533.


29

89. Miller, B. Advanced Organic Chemistry. 2nd Ed. Upper Saddle River:

Pearson Prentice Hall. 2004.


30

CHAPTER II

COMPUTATIONAL STUDIES OF SIGMATROPIC REARRANGEMENT OF

ALLYLIC AND VINYLOGOUS AZIDES

2.1 AZIDE CHEMISTRY

Azide chemistry was first introduced in the 1864 with discovery of phenyl

azide by Peter Griess. 1,2

The chemistry of these electron rich and flexible

intermediates broadened after important contributions by Curtius who developed

hydrogen azide and discovered the rearrangement of acyl azide to corresponding

isocyanates (Curtius rearrangement).3,4

However, the organic azides started receiving

considerable attention in the 1950s and 1960s5,6

with new applications in the

chemistry of the acyl, aryl and alkyl azides. Synthesis of hetrocycles such as triazoles

and tetrazoles as well as with their use as blowing agents and as functional groups in

pharmaceuticals led to the extensive use of organic azide compounds for industrial

purposes.7-11

AZT (an azidonucleoside) is an organic azide compound that is used for

treatment of AIDS.12

Azides are considered as the first and foremost energy-rich molecules which

often exhibit explosive properties. The azido group is considered to be the highly

energetic functional group. The N3 π-bond easily polarizes which consequently

results in strong exothermic dissociation reactions leading to release of molecular

nitrogen and reactive nitrene groups. It has been reported that the introduction of

azido group into an organic compound increases its energy content by approximately


31

290-355 kJ/mol13,14

which makes organic azides useful for the preparation of

energetic materials such as energetic polymers or high-energy-density materials in

explosives or propellant formation (NaN3 is the propellant used in the air bags of

automobiles).15,16

However, the poor thermal and mechanical stability of many

organic azides sometimes make them impractical to use.

Organic azides have a variety of chemical diversity because of the

physicochemical properties of azides. Some of these properties of organic azides are

explained by the resonance structures of azides, which have different dipolar

characteristics as shown in Figure 2.1.

Figure 2.1: Representative resonance structures of azides.

The structures 1c and 1d which were proposed by Pauling17,18

explain the

facile decomposition into corresponding nitrene and dinitrogen as well as the

reactivity as a 1,3-dipole. The regioselectivity of the reaction with an electrophile or

nucleophile can be explained by the mesomeric structure 1d. Azide ions are known as

pseudohalides as the electronegativitiy value of N3 (7.7eV) which is very close to that

of Cl (8.3eV) and Br (7.5eV).19,20

The most common types of reactions encountered by azides are: 21


32

1. Unimolecular Decomposition by Light or Heat: It generates singlet or triplet

nitrenes. The possible reaction pathways are summarized in Figure 2.2 and

discussed in more detail below.

Figure 2.2: Products from unimolecular decomposition of azides.

a. Nitrene-Derived Products: 21

The more electron-attracting is R, the

more electrophilic will be the singlet nitrene, so promoting its

reactions relative to those of the triplet nitrene.

Figure 2.3: Nitrene products from azides.

b. Rearrangement followed by Nucleophilic Attack22

Figure 2.4: Rearrangement products from azides.


33

c. Zwittazido Cleavage: 23

Zwittazido cleavage is represented by the ring

contraction (path A, as shown in Figure 2.5(a)) or fragmentation (path B, as

shown in Figure 2.5(a)) of appropriately substituted vinyl azides. The

fragmentation mode since to date is the only synthetically useful route to

cyanoketenes as shown in Figure 2.5(b).

(a)

(b)

Figure 2.5: Zwittazido cleavage of azides (a) general mechanisms, (b) a specific

example.23


34

2. Acid- Catalyzed Decomposition24

Figure 2.6: Mechanism of acid-catalyzed decomposition.

3. Staudinger Reaction25

Figure 2.7: Mechanism of Staudinger Reaction.

4. Curtius Rearrangement26

Figure 2.8: Mechanism of Curtius Rearrangement.

5. Schmidt Rearrangement27

Figure 2.9: Reaction of Schmidt Rearrangement.


35

6. Reduction28

Figure 2.10: Reaction showing reduction.

7. Cycloadditions29

Figure 2.11: Reaction showing cycloaddition.

8. Nucleophilic Attack at the Azide Terminus30

Figure 2.12: Mechanism showing nucleophilic attack at the azide terminus.

2.2 SIGMATROPIC REARRANGEMENT OF ALLYLIC AZIDES

As mentioned in Section 2.1 organic azides represent an important class of

compounds for organic synthesis and material sciences. There have been extensive

studies on the reactivity of organic azides. However, among this family, allylic azides

have not been explored as much. The synthesis of allylic azides is complicated as they

undergo [3, 3] sigmatropic rearrangement as shown in Figure 2.13.31


36

Figure 2.13: [3, 3] Sigmatropic rearrangement of allyl azide (1).

[3, 3] Sigmatropic rearrangements of acyclic allylic azides have been reported

at or below room temperature.32

But cyclic allylic azides seem to require higher

temperatures to rearrange. Indeed, it has been seen that most allylic azides exist as

mixtures of regioisomers that interconvert rapidly at ambient temperature. This is a

major drawback which hampers the use of allylic azides in synthesis. It has also been

reported that, in general, tertiary and secondary allylic azides rearrange much more

rapidly than primary allylic azides.33

In addition, the regioisomer with the more

substituted alkene are usually thermodynamically more favored. Hence, a high degree

of regioselectivity can be obtained in cases where the double bond is conjugated with

an unsaturation34

while some degree of regiochemical control is achieved using

competitive reactivity of either the azide or alkene moiety.35

Olefins are often considered stable in most acid/base environments, therefore

one expects that the special case of allylic azides might possess the familiar reactivity

profile, and it does, even though the azide and the olefins groups are engaged in

dynamic [3,3] sigmatropic equilibrium process as shown in Figure 2.14.36


37

Figure 2.14: Rearrangement of an allylic azide.36

[3, 3] Sigmatropic rearrangements like the Cope and the Claisen reactions have

been known for over 60 years. But it was not until 1954, when Vander Werf and

coworkers37

while studying the reaction of sodium azide with epoxides, observed that

the allylic case gave a mixture of regioisomers. Although the possibility of as SN2ʹ

attack could not be ruled out (Figure 2.15), they were the first to propose the

hypothesis that the resulting mixture could be result of sigmatropic rearrangement.


38

Figure 2.15: Concerted rearrangement vs. SN2ʹ attack. Top: the expected SN2 pathway

of nucleophilic opening of epoxide, 1; middle: allylic azide rearrangement of 2 leading

to 4-azido-2-buten-1-ol, 3; bottom: alternative SN2ʹ pathway leading to 4-azido-2-

buten-1-ol, 2.37

In 1960, Gagneux, Winstein and Young reported that allylic azides exist as

equilibrium mixture of regioisomers. They showed that α- and γ-methylallyl azide

rapidly form an equilibrium mixture of the two isomers (Figure 2.16).31a

Figure 2.16: Equilibrium between α- and γ-methylallyl azide.

The rates of the allylic azide rearrangements were found to be remarkably

insensitive to methyl substitution in the substrate azide or to solvent change. It was

also seen that the change from ground state to transition state in azide isomerization

involved a very little increase in polar character. And finially, no detectable solvolysis

competes with azide isomerization, even in 70% aqueous acetone.


39

The two mechanisms that were postulated to rationalize this equilibrium are

shown in Figure 2.17:38(a)

1. A concerted [3, 3] -sigmatropic rearrangement (Path A) in

which the sterochemical integrity of molecule is preserved.

2. A dissociative process involving ion-pair formation (Path B)

whereby the initial stereochemistry can be lost.

Figure 2.17: Possible mechanistic alternatives for the allylic rearrangement.

The remarkable insensitivity of the rearrangement to changes in solvent as well

as to alkyl substitution are indicative of very little charge separation in the transition

state, and it is generally assumed that the equilibration occurs via a cyclic transition

state (i.e., Path A). No definitive proof has been presented to date, however, which

unequivocally distinguishes between the above two mechanistic possibilities. Lacking

well-defined regio- and stereochemistry, the rearrangement has been underutilized and

no general approach to affecting a controllable stereoselective isomerization has been

reported.


40

Since then various groups38(b-i)

are using the concept of sigmatropic

rearrangement of allylic azide to provide mechanistic route and use them for the

purpose of syntheses of different useful compounds. Our main aim in this chapter is to

study [3, 3] sigmatropic rearrangement of the allylic azide through computational

studies and also our aim here is to study [3, 5] sigmatropic rearrangement of the

vinologous azide and distinguish them as pericylic or pseudopericyclic.

2.3 COMPUTATIONAL METHOD

All the computational calculations were carried out using Gaussian 03

program.39

The 6-31G(d,p) basis set40

was used throughout. Geometries were

completely optimized at using RHF/6-31G(d,p) , RMP2/6-31G(d,p) (ab initio second-

order Møller-Plesset perturbation)41-45

and Density Functional Theory using

RB3LYP/6-31G(d,p) (the hybrid three parameter function developed by Becke with

Lee-Yang-Parr correlation function).46-55

A systematic search with constrained

distance was performed at the RB3LYP/6-31G(d,p) level. Frequency calculations

verified the identity of each stationary point as a minimum or transition state. Zero-

point vibrational energies have been computed and have not been scaled. All energies

discussed here are the results of calculations at the RB3LYP/6-31G(d,p) + ZPE level.


41

2.4 RESULTS AND DISCUSSIONS

2.4.1 Study of the [3, 3] Sigmatropic Rearrangement of Allylic Azide

The geometry of allyl azide as shown in Figure 2.18 (a) was calculated in

different conformations. A transition state for degenerate rearrangement was also

located as described below. Molecular orbitals in Figure 2.18 (b) shows that three N-

atoms in azide are in same plane.

Initially, the C-N distance was constrained at various lengths to obtain an

energy profile for the reaction (Figure 2.19). This indicated a minimum energy

conformation near 1.50 Å and a transition state near 2.00 Å. The values of all relative

energies with constrained bond lengths are given in Table 2.1.

Figure 2.18: (a) [3, 3] Sigmatropic Rearrangement of allylic azide (1).

(b) Molecular orbital diagram of azide.


42

Table 2.1: The calculated absolute energies (Hartree), zero-point energies (ZPE,

kcal/mol), relative energies (kcal/mol with respect to ground state), relative energies

with zero-point energy correction (kcal/mol) of different models at different

constrained C-N bond length (Å) at the RB3LYP/6-31G(d,p) level of theory.

Constrained C-N

Bond Length

(Å)

Absolute

Energy

(Hartree)

Absolute

Energy

(kcal/mol)

ZPE

(kcal/mol)

Relative

Energy + ZPE

(kcal/mol)

1.50 -281.4936 -176640.04 52.80 40.49

1.75 -281.4785 -176630.59 51.83 49.46

2.00 -281.4601 -176619.01 51.36 62.47

2.25 -281.4659 -176622.65 52.79 59.05

2.50 -281.4755 -176628.69 53.01 0.00


43

Figure 2.19: Energy profile showing relative energy and constrained C-N bond

distance. This helps in determining which structure should be taken to optimize at

ground state and transition state.

The optimization was done for ground state using the structure at 1.50 Å,

removing the constraint on the bond length. The transition state was similarly found

beginning with the optimized geometry of the structure with a C-N bond length near

2.00 Å. Later an IRC (Intrinsic Reaction Coordinate) was run from transition state to

confirm the connection to the product (i.e. degeneracy of rearrangement). The other

conformations (1b-e) were found by rotating around the C-C and the C-N single

bonds. Four other conformations were located (Table 2.2).


44

Figure 2.20: IRC calculation of transition state of the allylic azide using the

RB3LYP/6-31G(d,p) level of theory.

Table 2.2: Dihedral angles (C-C-C-N and C-C-N-N) of ground state, transition state

and different conformers using RB3LYP/6-31G(d,p) level of theory.

Structure Dihedral angle

C-C-C-N

Dihedral angle

C-C-N-N

Ground State, 1a -120.7 64.8

Transition state, 5 -67.7 28.4

Conformation-1, 1b 0.02 -179.9

Conformation-2, 1c -1.8 -84.7

Conformation-3, 1d -127.1 -169.4

Conformation-4, 1e -118.8 -78.6


45

The results of the optimization of the ground state, the transition state, and four

other conformations at three different levels of theory are provided in Tables 2.3, 2.4

and 2.5. Also all the calculated thermodynamic quantities are given in Tables 2.6, 2.7

and 2.8.

Table 2.3: The calculated absolute energies (AE, Hartree), dipole moment (DM,

Debye), low or imaginary frequencies (LF, cm-1


absolute energies with zero-point energy correction (AE+ZPE, kcal/mol) and relative

energies with zero-point energy correction (RE, kcal/mol) for the stationary points of

the [3, 3] sigmatropic rearrangement reaction of allyl azide at the RB3LYP/6-31G(d,p)

level of theory.

Structure AE DM LF ZPE AE+ZPE RE

Ground State, 1a -281.4936 2.40 63.2 52.82 -176587.2352 0.00

Transition state, 5 -281.4555 2.96 372.3i 51.91 -176564.2434 22.99

Conformation-1, 1b -281.4925 2.20 27.4 52.64 -176586.6936 0.54

Conformation-2, 1c -281.4926 2.31 46.6 52.79 -176586.6001 0.64

Conformation-3, 1d -281.4920 2.41 32.7 52.59 -176586.4489 0.79

Conformation-4, 1e -281.4922 2.41 38.8 52.75 -176586.4392 0.80


46






the [3, 3] sigmatropic rearrangement reaction of allyl azide at the RHF/6-31G(d,p)

level of theory.


Ground State, 1a -279.7562 2.01 69.1 56.70 -175493.0823 0.00


Conformation-1, 1b -279.7543 1.85 24.7 56.51 -175492.1108 0.97

Conformation-2, 1c -279.7548 1.93 56.5 56.69 -175492.2329 0.85

Conformation-3, 1d -279.7544 1.96 35.6 56.47 -175492.2470 0.84

Conformation-4, 1e -279.7541 2.06 32.9 56.61 -175491.8871 1.20


47






the [3, 3] sigmatropic rearrangement reaction of allyl azide at the RMP2/6-31G(d,p)

level of theory.


Ground State, 1a -280.6730 2.27 58.0 53.94 -176071.1552 0.00


Conformation-1, 1b -280.6707 2.10 30.1 53.74 -176069.9310 1.22

Conformation-2, 1c -280.6717 2.22 71.1 53.94 -176070.3321 0.82

Conformation-3, 1d -280.6707 2.29 43.7 53.77 -176069.8737 1.28

Conformation-4, 1e -280.6713 2.38 57.2 53.94 -176070.1169 1.04


48

Table 2.6: Calculated thermodynamic data for the [3, 3] sigmatropic rearrangement of

allyl azide at the RB3LYP/6-31G(d,p) level of theory: sum of electronic and thermal

Gibbs free energies (G), sum of electronic and thermal enthalpies (H), and entropies

(S).

Structure G

(Hartree)

H

(Hartree)

S

(cal/mol.K)

Ground State, 1a -281.4401 -281.4022 79.7530

Transition state, 5 -281.4015 -281.3664 73.9800

Conformation-1, 1b -281.4396 -281.4013 80.6570

Conformation-2, 1c -281.4390 -281.4013 79.4370

Conformation-3, 1d -281.4392 -281.4008 80.9190

Conformation-4, 1e -281.4392 -281.4009 80.5790


49


allyl azide at the RHF/6-31G(d,p) level of theory: sum of electronic and thermal Gibbs

free energies (G), sum of electronic and thermal enthalpies (H), and entropies (S).

Structure G

(Hartree)

H

(Hartree)

S

(cal/mol.K)

Ground State, 1a -279.6961 -279.6589 78.2110


Conformation-1, 1b -279.6951 -279.6572 79.7880

Conformation-2, 1c -279.6946 -279.6576 77.8920

Conformation-3, 1d -279.6952 -279.6574 79.5370

Conformation-4, 1e -279.6947 -279.6569 79.6370


50


allyl azide at the RMP2/6-31G(d,p) level of theory: sum of electronic and thermal

Gibbs free energies (G), sum of electronic and thermal enthalpies (H), and entropies

(S).

Structure G

(Hartree)

H

(Hartree)

S

(cal/mol.K)

Ground State, 1a -280.6176 -280.5798 79.6140


Conformation-1, 1b -280.6161 -280.5777 80.7730

Conformation-2, 1c -280.6159 -280.5785 78.6710

Conformation-3, 1d -280.6158 -280.5776 80.3100

Conformation-4, 1e -280.6160 -280.5781 79.7030

Using the thermodynamic values in Table 2.6, 2.7 and 2.8, activation energy

Ea. and rate constant k were calculated using following formulas:

-

------ (eq.1)


51

( ) --------- (eq.2)

where Boltzmann constant, kb=1.38E-23 J K-1

, Plank’s constant, h=6.626E-34 J s,

T=298.15 K, Gas constant, R=1.98 cal K−1

mol−1

, concentration, c0=1, enthalpies of

activation (ΔH≠), Gibbs activation free energies (ΔG

≠).

Table 2.9: Activation parameters for the [3, 3] sigmatropic rearrangement of allyl

azide at three different level of theory using 6-31G(d.p) basis set using ground state

conformation (1a) as reference. (Gibbs activation free energy, (ΔG≠, kcal/mol),

Enthalpies of activation, (ΔH≠, kcal/mol), Entropy of activation, (ΔS

≠, cal/mol.K),

Activation energy, (Ea, kcal/mol) and Rate constant, (k, s-1

))

From Table 2.9 it is observed that the RHF method predicts a higher energy barrier,

RMP2 predicts a lower energy barrier while RB3LYP predicts an intermediate energy

barrier. These results are in agreement with previous studies56,57

which shows that RB3LYP

Level of theory ΔG≠ ΔH

≠ ΔS

≠ Ea k

RB3LYP 24.209 22.488 -5.773 23.08 1.09E-05

RHF 42.243 40.567 -5.617 41.16 6.43E-19

RMP2 18.667 16.727 -6.508 17.32 1.26E-01


52

level of theory are in closer agreement with experimental results as observed in many

pericyclic reactions.

After computing all the data an energy profile is made using calculation results

from RB3LYP/6-31G(d,p) as shown in Figure 2.21. The calculated energy barrier

(RE) for the [3, 3] sigmatropic rearrangement of the allyl azide with respect to ground

state (1a) is 23.08 kcal/mol (Table 2.9).

Figure 2.21: Energy profile (RE from Table 2.3) of the [3,3] sigmatropic

rearrangement of the allyl azide and different conformers of the allyl azide at

B3LYP/6-31G(d,p) level of theory, where GS stands for ground state (1a), TS for

transition state (5), C1 for conformation1 (1b), C2 for conformation-2 (1c), C3 for

conformation-3 (1d) and C4 for conformation-4 (1e). Their relative energies in

kcal/mol with respect to ground state are provided in parentheses.


53

The transition state geometry of the [3, 3] sigmatropic rearrangement of allyl

azide suggest that it is pericyclic in nature. Figure 2.22 shows different views of the

transition state.

Figure 2.22: Three different views of the transition state of the [3, 3] sigmatropic

rearrangement of allyl azide. Bond Lengths: C(6)-N(1) = 2.07 Å, C(4)-N(3) = 2.07 Å;

Bond Angles: N(1)-N(2)-N(3) = 163.13°, C(4)-C(5)-C(6) = 120.39°.


54

A reaction is pericyclic in name if the reaction proceeds in concerted manner

involving no charged intermediates with a single cyclic transition state.58

Furthermore,

textbook examples of pericyclic reactions have cyclic overlap. As seen in Figure 2.22

the [3, 3] sigmatropic rearrangement of allyl azide fits these criteria, including cyclic

orbital overlap between the allylic fragment and one of the two π-systems on the azide

fragment, hence it is pericyclic in nature.

Figure 2.14: Rearrangement of an allylic azide.36

As shown in Figure 2.14, 3-azido-1-butene (3) is an intermediate in the

interconversion of cis-1-azido-2-butene (4) and trans-1-azido-2-butene (2), via a

sequential [3, 3] sigmatropic rearrangements. RB3LYP/6-31G(d,p) calculations were

performed on this system; the results are summarized in Table 2.10 and Figure 2.23.

The transition state (6) for formation of trans-1-azido-2-butene from 3-azido-1-butene

(3) is 2.36 kcal/mol lower than that (7) for the cis-1-azido-2-butene (Table 2.12) but

both are low enough in energy to account for the rapid interconversion observed at

room temperature.32


55




absolute energies with zero-point energy correction (AE+ZPV, kcal/mol) and relative

energies with zero-point energy correction (RE, kcal/mol) for the stationary points for

the [3, 3] sigmatropic rearrangements of cis and trans-1-azido-2-butene at the



transǂ-1-azido-2-butene (6) -320.7793 3.31 333.2i 69.41 -201222.8036 22.30

cisǂ-1-azido-2-butene (7) -320.7757 3.25 343.6i 69.59 -201220.3668 24.73

cis-1-azido-2-butene (4) -320.8138 2.69 34.4 70.65 -201243.2431 1.86

trans-1-azido-2-butene (2) -320.8166 2.70 48.3 70.52 -201245.1006 0.00

3-azido-1-butene (3) -320.8143 2.41 54.3 70.33 -201243.8344 1.27


56

Table 2.11: Calculated thermodynamic data for the [3, 3] sigmatropic rearrangements

of cis and trans-1-azido-2-butene at the RB3LYP/6-31G(d,p) level of theory: sum of


enthalpies (H), and entropies (S).

Structure G

(Hartree)

H

(Hartree)

S

(cal/mol.K)

transǂ-1-azido-2-butene (6) -320.6995 -320.6607 81.7940

cisǂ-1-azido-2-butene (7) -320.6956 -320.6569 81.3410

cis-1-azido-2-butene (4) -320.7346 -320.6926 88.4150

trans-1-azido-2-butene (2) -320.7371 -320.6955 87.6360

3-azido-1-butene (3) -320.7347 -320.6936 86.5010

Table 2.12: Activation parameters for the [3, 3] sigmatropic rearrangements of trans-

1-azido-2-butene (2) and cis-1-azido-2-butene (4) from 3-azido-1-butene (3) at

RB3LYP/6-31G(d.p) level of theory using thermodynamic parameters from Table

2.11. (Gibbs activation free energy, (ΔG≠, kcal/mol), Enthalpies of activation, (ΔH

≠,

kcal/mol), Entropy of activation, (ΔS≠, cal/mol.K), Activation energy, (Ea, kcal/mol)

and Rate constant, (k, s-1

))

Structure ΔG≠ ΔH

≠ ΔS

≠ Ea k

transǂ-1-azido-2-butene (6) 22.052 20.649 -4.707 21.24 4.15E-04

cisǂ-1-azido-2-butene (7) 24.541 23.003 -5.160 23.60 6.20E-06


57

Figure 2.23: Energy profile (RE from Table 2.11) for the [3, 3] sigmatropic

rearrangements of cis and trans-1-azido-2-butene at the RB3LYP/6-31G(d,p) level of

theory, where trans-1-azido-2-butene (2), 3-azido-1-butene (3), cis-1-azido-2-butene

(4), trans-transition state (6) and cis-transition state (7). Their relative energies in

kcal/mol with respect to 2 are provided in parentheses.


58

Figure 2.24: Structure of trans-transition state (6). Bond Lengths: C(6)-N(1) = 2.11 Å,

C(4)-N(3) = 2.13 Å; Bond Angles: N(1)-N(2)-N(3) = 164.6°, C(4)-C(5)-C(6) =

121.3°, C(5)-C(6)-C(7) = 123.1°, N(1)-C(6)-C(7) = 153.6°.

Figure 2.25: Structure of cis-transition state (7). Bond Lengths: C(6)-N(1) = 2.13 Å,

C(4)-N(3) = 2.11 Å; Bond Angles: N(1)-N(2)-N(3) = 164.5°, C(4)-C(5)-C(6) =

122.9°, C(5)-C(6)-C(7) = 125.2°, N(1)-C(6)-C(7) = 97.0°.

2.4.2 Study of the [3, 5] Sigmatropic Rearrangement of Vinylogous

(Pentadienyl) Azide

After examining the [3, 3] sigmatropic rearrangement of allyl azide, our next

aim was to add a vinyl group to allylic structure. With a vinyl group added, the


59

vinylogous (pentadienyl) azide and the orthogonal π-system of the azide present the

possibility of an eight-centered pseudopericyclic transition state for a [3, 5]

sigmatropic rearrangement. The [3, 3] rearrangement of vinylogous azides are still

possible, these reactions are shown in Figure 2.26.

Figure 2.26: The [3, 3] and [3, 5] sigmatropic rearrangement of vinylogous azide (8).

The initial calculations were done using the RB3LYP/6-31G(d,p) level of

theory by constraining the C-N distance to find structures close to the possible

transition states. The calculations were done at bond lengths of 1.50 Å, 1.80 Å and

2.00 Å. The optimization for the transiton state using the structure calculated at 1.80

Å, removing the constrain on bond length, resulted in the structure of transition state-1

(11, Figure 2.27). Similar optimization of structure obtained at 2.00 Å resulted in the

structure of transition state-2 (14, Figure 2.28). After obtaining the transition state-1

(11) and transition state-2 (14), IRC (Intrinsic Reaction Coordinate) calculations

(Figure 2.27 a,b and Figure 2.28 a,b) were run on transition states in both directions to

obtain possible reactants and products. The structures obtained through the IRC

calculations were optimized to reactants and products. Optimizations were done to


60

obtain structures of possible [3, 3] rearrangement, product-4 (19) and transition state-

4 (18), Figure 2.29.

Figure 2.27: IRC run for transition state-1 (11): (a) IRC run in forward direction

towards possible product and (b) IRC run in reverse direction towards possible

reactant using RB3LYP/6-31G(d,p) level of theory.


61

As shown in Figure 2.27(a) IRC for transition state-1 (11) in forward direction

resulted in a structure which futher optimized to give structure 13 as product (Figure

2.29). Similarly, IRC calculations for transition state-1 (11) in reverse direction

(Figure 2.27 (b)) resulted in a structure which futher optimized to give structure 12 as

reactant (Figure 2.29). When IRC calculation for transition state-1 (11) in reverse

direction was checked there was a structure which looked like another transition state

(TS-3). The structure was optimized to obtain transition state-3 (17, Figure 2.29).

Figure 2.28: IRC calculations for transition state-2 (14): (a) IRC calculations in reverse

direction towards possible reactant and (b) IRC calculations in forward direction

towards possible product using RB3LYP/6-31G(d,p) level of theory.

IRC for transition state-1 (14) in forward direction (Figure 2.28 (b)) resulted in a

structure which futher optimized to give structure 16 as product (Figure 2.29). Similarly,

IRC calculations for transition state-1 (14) in reverse direction (Figure 2.28 (a)) resulted

in a structure which futher optimized to give structure 15 as reactant (Figure 2.29).


62

The results of all optimizations done for different reactants, transition states

and products at three levels of theory are provided in Tables 2.13, 2.14 and 2.15. Also

all the calculated thermodynamic quantities are given in Tables 2.16, 2.17 and 2.18.






the [3, 5] and [3, 3] sigmatropic rearrangements of the vinylogous azide at the



transition state-1 (11) -358.8145 4.11 512.8i 73.57 -225086.1357 48.79

reactant-1 (12) -358.8627 3.60 164.5 75.57 -225114.3378 20.59

product-1 (13) -358.8926 2.62 44.3 74.05 -225134.6329 0.29


reactant-2 (15) -358.8861 2.34 35.5 73.68 -225130.9458 3.98

product-2 (16) -358.8932 2.48 29.7 74.14 -225134.9240 0.00



product-4 (19) -358.8882 2.42 44.9 73.27 -225132.6676 2.26


63






the [3, 5] and [3, 3] sigmatropic rearrangements of the vinylogous azide at the RHF/6-

31G(d,p) level of theory.


transition state-1 (11) -356.5322 4.89 841.9 79.35 -223648.1933 66.96

reactant-1 (12) -356.6148 3.86 192.1 82.12 -223697.2306 17.93

product-1 (13) -356.6390 2.28 48.5 79.41 -223715.1560 0.00

transition state-2 (14) -356.5260 7.69 -500.9 77.52 -223646.0824 69.07

reactant-2 (15) -356.6148 3.86 41.9 79.39 -223699.9588 15.20

product-2 (16) -356.6386 2.05 28.2 79.51 -223714.7548 0.40



product-4 (19) -356.6371 1.96 53.4 78.72 -223714.6357 0.52


64






the [3, 5] and [3, 3] sigmatropic rearrangements of the vinylogous azide at the

RMP2/6-31G(d,p) level of theory.



reactant-1 (12) -357.7875 3.93 181.4 77.05 -224438.1787 24.38

product-1 (13) -357.8218 2.56 53.2 75.49 -224461.2655 1.29


reactant-2 (15) -357.8234 2.17 21.9 75.21 -224462.5557 0.00

product-2 (16) -357.8221 2.29 40.6 75.58 -224461.3380 1.22



product-4 (19) -357.8199 2.28 54.9 74.65 -224460.9034 1.65


65

Table 2.16: Calculated thermodynamic data for the [3, 5] and [3, 3] sigmatropic

rearrangements of the vinylogous azide at the RB3LYP/6-31G(d,p) level of theory:

sum of electronic and thermal Gibbs free energies (G), sum of electronic and thermal


Structure G

(Hartree)

H

(Hartree)

S

(cal/mol.K)

transition state-1 (11) -358.7279 -358.6896 80.5850

reactant-1 (12) -358.7724 -358.7350 78.6660

product-1 (13) -358.8085 -358.7653 90.9770


reactant-2 (15) -358.8034 -358.7592 93.1260

product-2 (16) -358.8092 -358.7658 91.2090



product-4 (19) -358.8058 -358.7619 92.2700


66


rearrangements of the vinylogous azide at the RHF/6-31G(d,p) level of theory: sum of



Structure G

(Hartree)

H

(Hartree)

S

(cal/mol.K)


reactant-1 (12) -356.5137 -356.4772 76.6230

product-1 (13) -356.5462 -356.5036 89.5970


reactant-2 (15) -356.5474 -356.5046 90.0320

product-2 (16) -356.5462 -356.5036 89.5970



product-4 (19) -356.5137 -356.4772 76.6230


67


rearrangements of the vinylogous azide at the RMP2/6-31G(d,p) level of theory: sum

of electronic and thermal Gibbs free energies (G), sum of electronic and thermal


Structure G

(Hartree)

H

(Hartree)

S

(cal/mol.K)


reactant-1 (12) -357.6947 -357.6576 78.1670

product-1 (13) -357.7351 -357.6923 89.9530


reactant-2 (15) -357.7382 -357.6942 92.7230

product-2 (16) -357.7352 -357.6925 89.9580



product-4 (19) -357.6947 -357.6576 78.1670


68

An energy profile summarizing the computational results at the RB3LYP/6-

31G(d,p) as shown in Figure 2.29.

Figure 2.29: Energy profile (RE from Table 2.13) for the [3, 5] and [3, 3] sigmatropic

rearrangements of vinylogous azide at the RB3LYP/6-31G(d,p) level of theory. Their

relative energies in kcal/mol with respect to 16 are provided in parentheses.

Optimization of structure 14 at transition state using UB3LYP/6-31G(d,p)

level of theory gave the same energy values hence showing that it does not have any

biradical character.

From Figure 2.29 it can be seen that the lowest energy transition state for [3, 5]

rearrangement is 14, hence 14 is used for calculating the activation energy and rate

constant for the [3, 5] rearrangement. Using thermodynamic quantities from Tables

2.16, 2.17 and 2.18 and eq. 1 and eq. 2, the rate constant (k) and activation energy (Ea)

for [3, 3] and [3, 5] sigmatropic rearrangements of vinylogous azide were calculated as

summarized in Table 2.19.


69

Table 2.19: Activation parameters for the [3, 5] and [3, 3] sigmatropic rearrangements

of vinylogous azide 16 and 19 from 15 at three different levels of theory using 6-

31G(d,p) basis set. (Gibbs activation free energy, (ΔG≠, kcal/mol), Enthalpies of

activation, (ΔH≠, kcal/mol), Entropy of activation, (ΔS

≠, cal/mol.K), Activation

energy, (Ea, kcal/mol) and Rate constant, (k, s-1

))

To study the rearrangement of vinylogous azide in detail, the dihedral angles

(C-C-C-N, C-C-N-N and C-C-C-C (Table 2.20)) of each structure was considered. As

our main interest in studying rearrangement depended on the transition states, Figures

2.30, 2.31, 2.32 and 2.34 were used to show different views of transition states.

Rearrangement Level of theory ΔG≠ ΔH

≠ ΔS

≠ Ea k

[3.5] RB3LYP 43.532 41.824 -5.728 42.42 7.30E-20

[3.3] RB3LYP 16.480 14.604 -6.294 15.20 5.07E+00

[3.5] RHF 70.766 69.570 -4.009 70.16 7.71E-40

[3.3] RHF 38.329 36.749 -5.298 37.34 4.78E-16

[3.5] RMP2 52.150 49.731 -8.112 50.32 3.48E-26

[3.3] RMP2 16.467 14.440 -6.797 15.03 5.18E+00


70

Table 2.20: Dihedral angles of various structures of vinylogous azide rearrangements

using RB3LYP/6-31G(d,p) level of theory.

Structure Dihedral Angle

(N3-C4-C5-C6)

Dihedral Angle

(N2-N3-C4-C5)

Dihedral Angle

(C5-C6-C7-C8)

transition state-1 (11) -79.29 96.85 4.31

reactant-1 (12) -65.92 65.55 -3.07

product-1 (13) 118.71 -65.09 -2.25

transition state-2 (14) -53.22 118.76 -12.58

reactant-2 (15) 90.14 66.92 -1.95

product-2 (16) -46.64 126.92 -3.73

transition state-3 (17) -96.54 115.04 7.92

transition state-4 (18) 70.21 -27.58 -160.91

product-4 (19) 126.45 -173.70 125.23


71

Figure 2.30: Three different views of 11 using RB3LYP/6-31G(d,p) level of theory.

Bond Lengths: N(1)-C(8) = 1.69 Å, N(3)-C(4) = 1.48 Å; Bond Angles: N(1)-N(2)-

N(3) = 140.8°, N(2)-N(3)-C(4) = 121.7°, N(3)-C(4)-C(5) = 109.7°, C(6)-C(7)-C(8) =

129.3°; Dihedral angle: C(8)-N(1)-N(3)-C(4) = 25.7°.



N(3) = 174.2°, C(4)-C(5)-C(6) = 128.4°, C(6)-C(7)-C(8) = 126.2°; Dihedral angle:

C(8)-N(1)-N(3)-C(4) = -59.4°.


72



N(3) = 123.1°, N(2)-N(3)-C(4) = 101.9° C(4)-C(5)-C(6) = 61.4°, C(6)-C(7)-C(8) =

126.1°; Dihedral angle: C(8)-N(1)-N(3)-C(4) = -53.1°.



N(3) = 167.9°, N(2)-N(3)-C(4) = 93.9° C(4)-C(5)-C(6) = 122.1°, C(6)-C(7)-C(8) =

123.4°. Dihedral angle: C(6)-N(1)-N(3)-C(4) = -6.82°.

From Figure 2.31 it can be seen that the sigmatropic rearrangement of the

vinylogous azide is via a eight-centered transition state. Also, structure 14 is orbital

symmetry allowed due to two orbital disconnections involving azide fragement, where


73

lone pair from nitrogen at azide forms a new C-N bond becoming a new bonded pair

with simultaneous cleavage of existing C-N bond to form a new lone pair. Hence, it

shows that it is pseudopericyclic in nature.

2.5 CONCLUSION

The [3, 3] sigmatropic rearrangement of allyl azide was found to be pericyclic

with low barrier of 23.08 kcal/mol. The low barrier can be explained from the fact that

the geometry of transition state of allyl azide is appropriate for cyclic orbital overlap.

The high nucleophilicity of azide may also be a factor in the low barrier. Calculations

for the [3, 3] rearrangements of cis and trans-1-azido-2-butene also shows that the

barrier of their interconversion is very low. Hence, this offers an explanation of the

experimentally observed rapid interconversion of cis and trans at room temperature.

The vinylogous azide was calculated to undergo [3, 5] as well [3, 3]

sigmatropic rearrangement. However, the barrier for transition state (14) undergoing

[3, 5] rearrangement was found to be much higher than the barrier for transition state

(18) of [3, 3] rearrangement. The eight-centered transition state-2 (14) of vinylogous

azide was found to be pseudopericyclic, with two orbital disconnections on the azide

fragment. The high barrier for the [3, 5] rearrangement can be explained due to the

unfavorable geometry of transition state which is required to allow the orthogonal π-

orbitals of the azide to participate in the pseudopericyclic rearrangement.


74

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55. Houk, K. N.; Gonzalez, J.; Li, Y. Acc. Chem. Res. 1995, 28, 81.

56. Hermida-Ramón, J. M.; Rodríguez-Otero, J.; Cabaleiro-Lago, E. M. J. Phys.

Chem. A 2003, 107, 1651–1654.

57. Ji, H.; Li, L.; Xu, X.; Ham, S.; Hammad, L. A.; Birney, D. M. J. Am. Chem.

Soc. 2009, 131, 528–537.

58. (a) Woodward, R. B.; Hoffmann, R. Angew. Chem. 1969, 81, 797. (b)

Woodward, R. B.; Hoffmann, R. Angew. Chem. Int. Ed. Engl. 1967, 8, 781.

(c) Hoffmann, R.; Woodward, R. B. Science. 1970, 167, 825. (d)


81

Hoffmann, R.; Woodward, R. B. Acc. Chem. Res. 1968, 1, 17. (e)

Hoffmann, R.; Woodward, R. B. J. Am. Chem. Soc. 1965, 87, 2046.


82

CHAPTER III

SYNTHESIS OF PENTADIENYL ALCOHOL DERIVATIVES AND STUDY OF

THEIR POSSIBLE [3, 3] AND [3, 5] SIGMATROPIC REARRANGEMENTS

3.1 REARRANGEMENT OF ESTERS

3.1.1 Background

After initial discovery of [3, 3]-sigmatropic rearrangements their scope and

utility has been greatly expanded.1,2

A wide variety of methods have been reported for

promoting the Cope and the Claisen rearrangements, including the use of Brønsted

acids, Brønsted bases, Lewis acids, and transition metals. These developments led to

the use of milder reaction conditions and, therefore, the examination of more complex

and synthetically relevant substrates.3

Lewis and coworkers in late 1960’s were the first to observe the rearrangement

of allylic esters, also known as [1, 3]-dioxa-Cope rearrangement.4-6

They observed the

rearrangement in the gas phase and the reaction was proposed to be a sigmatropic

rearrangement, proceeding via a six-membered cyclic transition state as shown in

Structure 1 of Scheme 3.1. They also considered the possibility of a four-membered

cyclic transition state as shown in Structure 2 of Scheme 3.1.


83

Scheme 3.1

Unlike the closely related Claisen rearrangement, this reaction is an

equilibrium process, in which the product distribution is governed by the relative

thermodynamic stabilities of the two allylic isomers. Therefore, strategies that

recognize this are required for the [1, 3]-dioxa-Cope rearrangement to become

synthetically useful for high product selectivity. At the same time rearrangement of

allylic esters using a mild catalyst have shown some promising results.7

in related

work, Overman and co-workers found that both allylic acetates and allylic carbamates

rearranged in the presence of either mercury(II) 8, 9

or palladium(II) 10-12

catalysts gave

moderate to high levels of product selectivity as shown in Scheme 3.2. Use of

PdCl2(NCCH3)2 as catalyst gave a high level of chirality transfer with observed

enantiomeric selectivity of rearrangement of allylic acetates.10-12

This method has

been proven useful in the synthesis of several natural products, including steroids,13

amino acids,14

and prostaglandins.15

Overman classified the transition-metal-

catalyzed reactions as “cyclization-induced” rearrangements, proposing a unique

mechanism for rearrangement of esters. The key feature of this mechanism was that

the metal acted as an electrophilic catalyst, binding to the alkene and activating it

toward nucleophilic attack by the pendant carbonyl oxygen to generate a cyclic,

organometallic intermediate 3 as shown in Scheme 3.3.7


84

Scheme 3.2

Scheme 3.3: Proposed mechanism of “cyclization-induced” rearrangements.7

3.1.2 Computational Study on Rearrangement of Esters

Wessely and coworkers16

observed that acyloxycyclohexadione 4 undergoes

thermal rearrangements. The observed phenol products, 7 and 9 were proposed to arise

from tautomerization of the rearranged acyloxycyclohexadiones 5 and 8 (and the acyl

migration of 6 to 7, Scheme 3.4). These authors proposed competing [3, 3] and [3, 5]

sigmatropic rearrangements, to form 5 and 8, respectively. They could not rule out

sequential [3, 3] rearrangements of 4 to 8 to 5. This work was published prior to the

Woodward-Hoffmann rules.50

Subsequent publications assumed that, the [3, 5]

rearrangement was forbidden, in analogy to the hydrocarbon system, until Birney et al.

revisited the system.17


85

Scheme 3.4

Birney and coworkers17

who were interested in study of pseudopericyclic

reactions, choose 2,4-cyclohexadienyl formate (10) as a model system (Scheme 3.5)

for understanding the rearrangements of acyloxycyclohexadiones seen earlier. They

calculated that the barrier for the [3, 5] sigmatropic rearrangement of 10 to 10 was 3.0

kcal/mol lower than the calculated barrier for the related [3, 3] sigmatropic

rearrangement of 10 to 11. This is because the [3, 3] rearrangement has a boat-shaped

transition state whereas the [3, 5] rearrangement has a transition state,

pseudopericyclic in nature, with the breaking and forming bonds in the same plane of

the ester. Figure 3.1 shows the calculated geometries and energies of the structures

involved in the rearrangements.


86

Scheme 3.5

Figure 3.1: Energy profile showing the [3, 3] rearrangement of 2,4-cyclohexadienyl

formate, 10 to 11 (right side) and the degenerate [3, 5] rearrangement of 2,4-

cyclohexadienyl formate, 10 (left side), with their transition states (10ǂ and 11

ǂ) in

between. The geometries were calculated at the MP2/6-31G** level of theory and the

relative energies were calculated at the MP4/6-31G** + ZPV (kcal/mol) level of

theory.17

They also did studies on simplest formate ester ((Z)-penta-2,4-dienyl formate,

12, Scheme 3.6) to possibly see the [3, 5] rearrangement.17

But instead the


87

optimization of transition state constrained to Cs symmetry led not to a [3, 5]

rearrangement but to a boat transition state for a [3, 3] rearrangement, 13, Scheme 3.6.

Figure 3.2 shows the schematic representation of the rearrangement. One conclusion

from this study is that a [3, 5] rearrangement to be allowed the distance between

reactive centers needs to be close enough for rearrangement to occur.

Scheme 3.6

Figure 3.2: Energy profile showing 12 forming a boat transition state leading to the

[3, 3] rearrangement of 13. The relative energies in kcal/mol were calculated at the

MP4/6-31G** level of theory.17


88

3.1.3 Proposed alcohol molecules

After carefully reviewing the calculation on esters, we wanted to study

possible [3, 3] and [3, 5] sigmatropic rearrangements of esters experimentally. Our

main aim was to design such as ester which can undergo both [3, 3] and [3, 5]

rearrangements. Hence, the selection of alcohol became an important factor. The

alcohol molecule was designed in such a way that the ester formed from alcohol

should have the oxygen (which would be one of the reactive centers) closer to C=C

where the rearrangement would take place. So, we examined a series of pentadienyl

alcohols (14-18). Compound 15 has the methanol group attached to a six-membered

ring (cyclohexene ring) with a vinyl group at the other end of the double bond. Also,

we added a phenyl group to the carbon next to alcohol in 16. All this was done to

make sure that it can form an eight-centered transition state. Then we did the same for

the five-membered ring structures as well (17 and 18). Table 3.1 shows the strain

energy, total energy and potential energy of each molecule was calculated using

MM2.51

Figure 3.3 and Figure 3.4 show the minimized structure of the proposed

pentadienyl alcohols for further experiments.


89

Table 3.1: Calculated strain energy, total energy and potential energy of minimized

structure of a series of pentadienyl alcohols using MM2.

Structure Strain Energy

(kcal/mol)

Total Energy

(kcal/mol)

Potential Energy

(kcal/mol)

OH

14

-2.03 24.66 9.86

OH

15

-1.14 43.28 23.35

OHPh

16

0.92 64.26 32.81

OH

17

-1.17 39.38 18.81

OHPh

18

0.41 57.46 27.40


90

16

Figure 3.3: MM2 minimized structure of phenyl(2-vinylcyclohex-1-enyl)methanol

(16, side viewed from two different directions) where blue are H-atoms, grey are

carbon atoms, red are oxygen atoms and pink are lone pair orbitals.

18

Figure 3.4: MM2 minimized structure of phenyl(2-vinylcyclopent-1-enyl)methanol

(18, side viewed from two different directions) where blue are H-atoms, grey are

carbon atoms, red are oxygen atoms and pink are lone pair orbitals.


91


acetate (25)

We proposed to synthesize phenyl(2-vinylcyclopent-1-enyl)methyl acetate, 25

(Figure 3.5) because one of the reactive centers (i.e. O from C=O) is closer to the

other (H attached to C=C). Also, it has enough strain to undergo not only [3, 3]-

sigmatropic rearrangement but also [3, 5]-sigmatropic rearrangement. The minimized

structures of proposed [3, 3] and [3, 5] rearranged products are shown in Figure 3.6.

Also, Table 3.2 shows the strain energy; total energy of molecule and potential energy

of different acetates and their rearranged products are calculated using MM2.


structures of various possible acetates and their possible [3, 3] and [3, 5] rearranged

products using MM2.

Structure Strain

Energy

(kcal/mol)

Total

Energy

(kcal/mol)

Potential

Energy

(kcal/mol)

Total Energy

difference in

rearrangement

(kcal/mol)

O

O

19

1.40 35.30 17.76 -

O

O

20

2.52 39.57 18.94 4.26


92

Table 3.2: Continued

Structure Strain

Energy

(kcal/mol)

Total

Energy

(kcal/mol)

Potential

Energy

(kcal/mol)

Total Energy

difference in

rearrangement

(kcal/mol)

O

O

21-cis

1.93 44.28 23.36 8.98

O

O

21-trans

1.57 41.89 19.89 6.59

O

O

22

3.13 53.77 24.93 -

O

O

23

5.19 56.00 33.55 2.06

O

O

24 (E)

8.87 58.57 32.64 5.74


93


Structure Strain

Energy

(kcal/mol)

Total

Energy

(kcal/mol)

Potential

Energy

(kcal/mol)

Total Energy

difference in

rearrangement

(kcal/mol)

O

O

24 (Z)

9.97 61.27 35.99 7.50

O

PhO

25

4.22 76.01 40.96 -

Ph

O

O

26

6.85 74.57 41.33 -1.44

Ph

O

O

27(E)

10.41 77.15 45.19 1.14

Ph

O

O

27(Z)

13.72 79.82 46.05 3.81


94

The results in Table 3.2 suggest that the [3, 5] sigmatropic rearrangement of acetate 25

is the least endothermic and might be anticipated to be observed.

25

Figure 3.5: MM2 minimized structure of phenyl(2-vinylcyclopent-1-enyl)methyl

acetate (25) where blue are H-atoms, grey are carbon atoms, red are oxygen atoms and

pink are lone pair orbitals.

Figure 3.6: MM2 minimized structure of [3, 3] (26) and [3, 5] (27) rearrangement

products from phenyl(2-vinylcyclopent-1-enyl)methyl acetate (25); where blue are H-

atoms, grey are carbon atoms, red are oxygen atoms and pink are lone pair orbitals.


95

The following scheme shows the methods used for the synthesis of phenyl(2-

vinylcyclopent-1-enyl)methyl acetate (25, Scheme 3.7).

Scheme 3.7


acetate (33)

Along the same lines we decided to study the rearrangement on phenyl(2-

vinylcyclohex-1-enyl)methyl acetate (33, Figure 3.7). We examined the MM2

minimized structures of all different acetates with possible [3, 3] and [3, 5]

sigmatropic rearrangements as shown in Table 3.3.


96


structures of various possible acetates and their possible [3, 3] and [3, 5] rearranged

products using MM2.

Structure Strain

Energy

(kcal/mol)

Total

Energy

(kcal/mol)

Potential

Energy

(kcal/mol)

Total Energy

difference in

rearrangement

(kcal/mol)

O

O

30

2.61 60.80 30.69 -

OO

31

7.65 63.31 35.84 2.51

O

O

32 (E)

5.95 61.78 35.54 0.98

O

O

32 (Z)

5.88 60.31 35.55 -0.49

PhO

O

33

8.01 78.76 44.68 -


97


Structure Strain

Energy

(kcal/mol)

Total

Energy

(kcal/mol)

Potential

Energy

(kcal/mol)

Total Energy

difference in

rearrangement

(kcal/mol)

Ph

OO

34

10.83 82.83 46.03 4.07

Ph

O O

35(E)

6.79 80.73 40.56 1.97

Ph O

O

35(Z)

6.50 80.33 41.80 1.57


98

33

Figure 3.7: MM2 minimized structure of phenyl(2-vinylcyclohex-1-enyl)methyl

acetate (33) where blue are H-atoms, grey are carbon atoms, red are oxygen atoms and

pink are lone pair orbitals.

Figure 3.8: MM2 minimized structure of [3, 3], 34 and [3, 5], 35 rearrangement

products from phenyl(2-vinylcyclohex-1-enyl)methyl acetate (33); where blue are H-

atoms, grey are carbon atoms, red are oxygen atoms and pink are lone pair orbitals.


99

The synthesis of phenyl(2-vinylcyclohex-1-enyl)methyl acetate (33, Scheme 3.8) was

similar to that of 25 (above).

Scheme 3.8

3.1.6 Flash Vacuum Pyrolysis

Flash vacuum pyrolysis (FVP) is experimental technique involving the vacuum

sublimation or distillation of a substrate through a hot tube (generally at temperatures

between 300–1000 °C) to induce chemical change. After passing through the tube, the

products are quenched at low temperatures in a trap placed at the exit point of the

tube.18,19

The pyrolysis therefore takes place under dilute, short contact time

conditions in the gas phase such that individual molecules react intramolecularly in the

effective absence of other molecules of substrate, product or substantial amounts of

oxygen. The technique is therefore known to produce much cleaner results than other

forms of pyrolysis. Flash Vacuum Pyrolysis is a robust, highly reproducible method

and has found widespread use in applications ranging from matrix isolation and


100

mechanistic studies to preparative organic chemistry.20

As is the case with any method

which depends on gas flow, the residence time of substrate molecules in the hot

(reacting) zone is a key parameter,21

and this in turn depends on a number of variables

including the pressure and temperature, the dimensions of the tube, throughput rate

and the presence of any material.21

Whereas static pyrolysis which are usually carried out in a sealed tube or by

reflux in presence of some solvent, for a longer period of time, this sometimes does

not yield clean products. However, in a flow system for FVP, compounds are exposed

to heat for short time and the pyrolysates are cooled immediately to very low

temperatures. This prevents bimolecular reactions from happening. Therefore, flash

pyrolysis requires higher temperatures to compensate for the short contact times.22

The

FVP method is used to study highly reactive intermediates or very unstable organic

compounds. The compounds or fragments formed in the pyrolysis are immediately

cooled down to -198 °C or trapped by other compounds so they can be further studied.

The method can also be used preparatively for synthesis of larger amounts of

compounds. For example, FVP of indanetrione and of phthalic anhydride as shown in

Scheme 3.9.23


101

Scheme 3.9

In our experiment we were studying the rearrangement of phenyl(2-

vinylcyclopent-1-enyl)methyl acetate (25) and phenyl(2-vinylcyclohex-1-enyl)methyl

acetate (33) in which a C-O bond had to be broken. The enthalpy of C-O bond is 358

kJ/mol which meant that C-O bond breaking would require a large amount of energy.

Experimental Procedure used for flash vacuum pyrolysis

The Flash Vacuum Pyrolysis technique was used to study rearrangement of

phenyl(2-vinylcyclopent-1-enyl)methyl acetate (25) and phenyl(2-vinylcyclohex-1-

enyl)methyl acetate (33). The experiment was carried out between 270-370 °C on the

apparatus as shown in Figure 3.9.


102

Figure 3.9: Flash Vacuum Pyrolysis (FVP) setup.

Table 3.4: Flash Vacuum Pyrolysis (FVP) experimental setup.

Number Description

1 Quartz tube with one end closed, sample is placed directly in quartz tube- the

quartz tube used is 66 cm length and 2.54 cm in diameter.

2 Digital thermometer

3 Pyrolysis oven, Heavy duty Heating Equipment

4 U-shape product collector tube

5 Dewar flask- used for cooling the pyrolysates at -198 °C

Approximately 100-200 mg of sample (25 or 33) was dissolved in anhydrous

diethyl ether (because they are very viscous, they need to be diluted for transfer) was

placed in the quartz tube (1). A vacuum of 0.1 torr was drawn on the quartz tube to

remove residual solvents such as diethyl ether, hexane or ethyl acetate. Then the


103

equipment was set up as shown in Figure 3.9. The liquid nitrogen bath is kept under

the U-tube to cool the pyrolysates. The pyrolysis oven was adjusted to a proper

temperature and the digital thermometer was set in the middle of the oven to read the

temperature of the oven. After the oven had reached a required temperature, the closed

end of the quartz tube was slowly pushed inside the oven. This was continued until the

closed end of the tube had gone inside the oven and the sample had vaporized the

quartz tube. The products were collected either at the end of the end of quartz tube or

in the U-tube. After the pyrolysis tube cooled, the system was filled with nitrogen. The

U-tube was removed from the system and warmed up to room temperature. A 1H-

NMR spectrum was obtained for crude the pyrolysis products collected both at the end

of the pyrolysis tube and in the U-tube. The samples obtained were then

chromatographed on silica gel column using 2% ethyl acetate solution in hexane to

separate the different products. The verification of products formed was done by 1H-

NMR and 13

C-NMR.

3.1.7 Result and Discussion

Although Flash Vacuum Pyrolysis experiments are highly reproducible using

one set of apparatus, the variables are often not specified in literature reports of FVP

applications, so it can be difficult to reproduce such conditions in another laboratory

without carrying out a series of trial experiments. In the work described here, we have

therefore systematically performed the experiments at varied temperatures and

monitored the effect of temperature on conversion to products.


104

The possible products of pyrolysis of phenyl(2-vinylcyclopent-1-enyl)methyl

acetate (25, Scheme 3.10).

Scheme 3.10

However, when we conducted pyrolysis of phenyl(2-vinylcyclopent-1-enyl)methyl

acetate (25) which gave the following results (Table 3.5):

Table 3.5: Products formed on pyrolysis of phenyl(2-vinylcyclopent-1-enyl)methyl

acetate (25) at two different temperatures.

Temperature Product formed

270-280°C 1. Only starting material, 25 (analyzed by 1H-NMR)

300-330°C

1. The 1H-NMR of the crude was a mixture of starting material and

possible peaks for [3, 5] rearranged product (27(E) or 27 (Z)).

2. Starting material, 25, 80% (obtained from column

chromatography on silica gel using 2% ethyl acetate in hexane).

3. Possibly small amount of [3, 5] rearrangement, 27 (obtained

from column chromatography) was a mixture with starting

material 25 (1H-NMR shown in Figure 3.10). The possible [3, 5]

rearrangement product, 27 is either due to expected [3, 5]

rearrangement (27-Z) or two sequential [3, 3] rearrangements

(27-E).


105

Figure 3.10: 1H-NMR from FVP of 25, obtained from column chromatography where

boxed signals in region from 8.75 ppm to 5.00 ppm are possibly from [3, 5] rearrangement.


106

Though we were able to see possibility of small amount of [3, 5]

rearrangement with a mixture of starting material (analysis done with 1H-NMR and

13C-NMR) but this experiment still needs to be optimized to get the exact ratio of

rearrangement. It needs to be conducted at various temperatures and a study of the

different products formed with increasing temperature may allow the differentiation of

direct [3, 5] as compared to sequential [3, 3] rearrangement mechanism.

The possible products of pyrolysis of phenyl(2-vinylcyclohex-1-enyl)methyl

acetate (33) are shown in Scheme 3.11.

Scheme 3.11

However, when we conducted pyrolysis of phenyl(2-vinylcyclohex-1-enyl)methyl

acetate (33) which gave the following results (Table 3.6):


107

Table 3.6: Products formed on pyrolysis of phenyl (2-vinylcyclohex-1-enyl) methyl

acetate (33) at three different temperatures.

Temperature Product formed

330-350°C 1. β-elimination, 37 as major product, 40% (after column chromatography

in silica gel using 2% ethyl acetate in hexane).

2. Starting material, 33 (after column chromatography).

3. Possibly small amount of [3, 5] rearrangement, 35 (obtained from

column chromatography) was a mixture with starting material 33 (1H-

NMR shown in Figure 3.11). The possible [3, 5] rearrangement product,

35 is either due to expected [3, 5] rearrangement (35-Z) or two

sequential [3, 3] rearrangements (35-E).

350-370°C 1. Completely dissociated to give an unidentified product containing

phenyl group (analyzed by 1H-NMR).

303-330°C 1. β-elimination, 37, 50% (after column chromatography).

2. Starting material, 33 (after column chromatography).

In case of phenyl(2-vinylcyclohex-1-enyl)methyl acetate (33) we were able to

identify 37 as the major product from the pyrolysis at 330 to 350 °C and also 303 to

330 °C. This presumably is formed by β-elimination from 34. There were also peaks

on 1H-NMR and

13C-NMR from the pyrolysis at 330-350 °C that could correspond to

35, the expected product from [3, 5] rearrangement (or two sequential [3,3]

rearrangements). We also need to repeat this experiment at several different


108

temperatures to see if we can observe more of the [3, 5] product and the possibility of

the [3, 3] product as well.

Figure 3.11: 1H-NMR from FVP of 33, obtained from column chromatography

where boxed signals in region between 6.6 ppm to 4.50 ppm are possibly from [3, 5]

rearrangement.

3.2 REARRANGEMENT OF TRICHLOROACETIMIDATES

3.2.1 Background

The thermal rearrangement of allylic imidates (e.g. 38 to 39) also known as the

“aza-Claisen” or “Claisen-imidate”, was discovered in 1937.24

Since then a number of

systems have been investigated for the practical preparation of allylic amides like

urethanes, isourethanes, formimidates, benzimidates, isourears and


109

carbonimidothioates. However, it is the discovery and development of the

rearrangement of allylic trichloroacetimidates that has led to the widest application

(Scheme 3.12).25-27

Scheme 3.12: Rearrangement of allylic trichloroacetimidates.

The [3, 3]-sigmatropic rearrangement of allylic tricholoroacetimidates is

generally referred to as Overmann rearrangement. It is conveniently carried out either

thermally or with Hg(II) or Pd(II) catalysis.28

The scope of the rearrangement is

readily accessible for primary, secondary, and tertiary allylic amides, thus providing

entry into a wide variety of nitrogen-containing products including amino sugars,

nucleotides, amino acids, peptides, and various nitrogen heterocycles. In addition, the

Overman rearrangement has found extensive application in the total synthesis of

natural products. Also, the development of chiral Pd(II) catalysts to promote

asymmetric allylic trichloroacetimidates rearrangements with good enantioselectivity

bodes well for the continued with broad application of the amine synthesis.29-31

Mechanism of Thermal rearrangements

The thermal rearrangement of allylic trichloroacetimidates is an irreversible

process because the enthalpy or driving force associated with conversion of the

imidate (e.g. 38) to the amide (e.g. 39) functionality is very large.32

The thermal [3, 3]


110

sigmatropic rearrangement occurs via a concerted process via a cyclic six-centered

transition state as shown in Figure 3.12.33

The activation parameters observed for the

allylic trichloroacetimidates rearrangement are ΔH#= 24 kcal/mol and ΔS

#= -19 eu,

which are typical of those observed for other [3, 3]-sigmatropic rearrangements.34

Hence, only small increases in rate35

are observed upon changing solvent from xylene

to nitrobenzene. Larger increased rate are the result of the attachment of carbocation

stabilizing groups to the imidate bearing carbon suggesting that some charge

separation in the transition state.

Figure 3.12: Cyclic six-centered transition state of the [3, 3] rearrangement of allylic

imidates where R, R1, R2, R3, R4 are various alkyl groups.

An example of the thermal rearrangement of trichloroacetimidic ester derived

from secondary alcohol, gave exclusively (E)-trichloroacetimidates, which is expected

from the large steric bulk of the tricholomethyl substitutent and the usual chair model

for the cyclic six-membered transition state (shown in Scheme 3.13).36

However, a

pseudopericyclic transition state (planar on the imidate) is also possible.


111

Scheme 3.13

Mechanism of Metal-Catalyzed Rearrangements

The rearrangement of allylic trichloroacetimidates using metal catalysts not

only lowers the temperature required for rearrangement but also leads to higher yields,

cleaner reactions and better sterocontrol. Many allylic trichloroacetimidates, ranging

from simple allylic trichloroacetimidates to highly functionalized substrates, rearrange

rapidly in presence of Pd(II) or Hg(II) catalysts. A cyclization-induced rearrangement

mechanism in which the metal coordinates to the allylic double bond to bring about

antarafacial intramolecular nucleophilic attack by the imidate nitrogen is believed to

be involved in Pd(II)- or Hg(II)-catalyzed rearrangements (as shown in Scheme

3.14).37


112

Scheme 3.14


2,2,2-trichloroacetimidate (41)

As a part of our effort to explore the differences between pericyclic and

pseudopericyclic reactions we decided to study the [3, 3] and [3, 5] sigmatropic

rearrangement of phenyl(2-vinylcyclopent-1-enyl)methyl 2,2,2-trichloroacetimidate

(41, Figure 3.13). We calculated the MM2 strain energy, total energy and potential

energy of minimized structures of trichloroacetimidate (41) and possible [3, 3], (42)

and [3, 5], (43) sigmatropic rearrangement products as shown in Table 3.7. The

calculated MM2 energies suggest that the [3, 5] rearrangement of 41 may be less

favored as compared to that of acetate 25.


113

41

Figure 3.13: MM2 minimized structure of phenyl(2-vinylcyclopent-1-enyl)methyl

2,2,2-trichloroacetimidate (41) where blue are N-atom, grey are C- atoms, red are O-

atom, pink are lone pair orbitals, green are Cl-atoms and white are H-atoms.


114


structures of trichloroacetimidate, 41 and their possible [3, 3], (42) and [3, 5], (43)

rearranged products using MM2.

Structure Strain

Energy

(kcal/mol)

Total

Energy

(kcal/mol)

Potential

Energy

(kcal/mol)

Total Energy

difference in

rearrangement

(kcal/mol))

O

Ph NH

CCl3

41

5.90 74.18 40.32 -

NHCOCCl3

Ph

42

-3.03 63.15 29.27 -11.03

Ph

NHCOCCl3

43(E)

4.77 72.12 40.61 -2.06

Ph

NHCOCCl3

43(Z)

7.62 70.43 38.61 -3.75


115

Trichloroacetimidates are readily prepared by the reaction of alcohols with

trichloroacetonitrile (Cl3CCN) with base catalysis. Several bases were screened for the

preparation of phenyl(2-vinylcyclopent-1-enyl)methyl 2,2,2-trichloroacetimidate (41)

from the alcohol 18 (Scheme 3.15). The best results were obtained with 0.1 eq. of

DBU relative to the alcohol.

Scheme 3.15


2,2,2-trichloroacetimidate (44)

We also decided to study the [3, 3] and [3, 5] sigmatropic rearrangement of

phenyl(2-vinylcyclohex-1-enyl)methyl 2,2,2-trichloroacetimidate (44, Figure 3.14).

We calculated MM2 strain energy, total energy and potential energy of minimized

structures of trichloroacetimidate, 44 and possible [3, 3], (45) and [3, 5], (46)

sigmatropic rearrangement products as shown in Table 3.8. These results suggest that

the [3, 5] rearrangement to form 46 may be favored.


116

44

Figure 3.14: MM2 minimized structure of phenyl(2-vinylcyclohex-1-enyl)methyl

2,2,2-trichloroacetimidate (44) where blue are N-atom, grey are C- atoms, red are O-

atom, pink are lone pair orbitals, green are Cl-atoms and white are H-atoms.


117


structures of trichloroacetimidate, 44 and their possible [3, 3], (45) and [3, 5], (46)

rearrangement products using MM2.

Structure Strain

Energy

(kcal/mol)

Total

Energy

(kcal/mol)

Potential

Energy

(kcal/mol)

Total Energy

difference in

rearrangement

(kcal/mol)

O

Ph NH

Cl3C

44

5.00 95.18 53.69 -

NHCOCCl3

Ph

45

1.52 69.46 34.60 -22.72

Ph

NHCOCCl3

46(E)

2.12 69.20 33.77 -26.98

Ph NHCOCCl3

46(Z)

2.64 66.37 32.66 -28.81


118

The synthesis of phenyl(2-vinylcyclohex-1-enyl)methyl 2,2,2-trichloroacetimidate

(44, Scheme 3.16) from the alcohol, 16 was carried out similarly to that of 41, above.

Scheme 3.16

3.2.4. Results and Discussion

We tried to synthesize compound 41 and compound 44 at different

temperatures (-78 °C, -20 °C, 0 °C and r.t.) using different solvents (ether, DCM and

toluene) and bases (NaH, KH and DBU). The crude NMR spectra showed compounds

41 and compound 44. However, these were very reactive and rearranged to [3, 3]

products (as evident in 1H-NMR) as shown in Scheme 3.17 and 3.18. The problem

with this is that we have not been able to separate the products and also have not been

able to calculate the ratio of sigmatropic rearrangement. Further experiments are

ongoing to stabilize trichloroacetimidates and study the [3, 3] as well as possible [3, 5]

rearrangements under controlled conditions.


119

Scheme 3.17: Possible products from sigmatropic rearrangement of phenyl(2-

vinylcyclopent-1-enyl)methyl 2,2,2-trichloroacetimidate (41)

Scheme 3.18: Possible products from sigmatropic rearrangement of phenyl(2-

vinylcyclohex-1-enyl)methyl 2,2,2-trichloroacetimidate (44)

3.3 REARRANGEMENT OF XANTHATES

3.3.1 Background

The formation of allylic sulfur compounds by [3, 3]-sigmatropic

rearrangements of allylic thiocarbonyl compounds, promoted thermally38

or by metal-

catalyzed cyclization induced rearrangement mechanisms,39-41

typically is not

complicated by issues of regioselectivity. The [3, 3]-sigmatropic rearrangement


120

reactions of allylic xanthates can be treated as gas-phase reactions because they are not

sensitive to the change in solvent polarity.

Harano42

and coworkers performed computational calculations using

MINDO/3 on O-allyl-S-methyl xanthate to study the [3, 3] sigmatropic rearrangement

of this representative allylic xanthate to form S-allyl S-methyl dithiocarbonate as

shown in Figure 3.15. The calculated energy profile shows that S-allyl S-methyl

dithiocarboante is 12 kcal/mol more than O-allyl- S-methyl xantate, suggesting that

the thione-to-carbonyl isomerization is exothermic.

Figure 3.15: Energy profile showing the [3, 3] sigmatropic rearrangement of allylic

xanthates calculated at the MINDO/3 level of theory.42


121

3.3.2 Proposed synthesis of S-methyl O-phenyl (2-vinylcyclopent-1-

enyl) methyl carbonodithioate (47)

We also wanted to study the [3, 3] and [3, 5] sigmatropic rearrangement when

a S-atom is replaced at the position of O-atom and N-atom in 25 and 41 respectively.

So, we decided to study rearrangement of S-methyl O-phenyl (2-vinylcyclopent-1-

enyl) methyl carbonodithioate (47, Figure 3.16). We calculated the MM2 strain

energy, total energy and potential energy of minimized structures of xanthates and

possible [3, 3] (48) and [3, 5] (49) sigmatropic rearrangements as shown in Table 3.9.

The product from [3, 5] rearrangement, 48 is more stable than that from the [3, 3]

rearrangement, 49, suggesting this might be observed.

47

Figure 3.16: Minimized structure of S-methyl O-phenyl (2-vinylcyclopent-1-enyl)

methyl carbonodithioate (47) where yellow are S-atom, grey are C- atoms, red are O-

atom, pink are lone pair orbitals, and white are H-atoms using MM2.


122


structures of xanthate, 47 and its possible [3, 3] (48) and [3, 5] (49) rearrangement

products using MM2.

Structure Strain

Energy

(kcal/mol)

Total

Energy

(kcal/mol)

Potential

Energy

(kcal/mol)

Total Energy

difference in

rearrangement

(kcal/mol)

Ph

O

S

S

47

5.31 74.54 39.33 -

S

Ph

O

S

48

5.26 72.15 38.60 - 2.39

Ph

S

O

S

49(E)

5.60 70.28 39.19 - 4.26

Ph

S

O

S

49(Z)

10.95 74.14 41.08 - 0.40


123

The synthesis of S-methyl O-phenyl (2-vinylcyclopent-1-enyl) methyl

carbonodithioate (47) was attempted from the alcohol, 18 (Scheme 3.19)

Scheme 3.19

3.3.3 Proposed synthesis of S-methyl O-phenyl (2-vinylcyclohex-1-

enyl) methyl carbonodithioate (50)

Similar studies on the [3, 3] and [3, 5] sigmatropic rearrangement of S-methyl

O-phenyl (2-vinylcyclohext-1-enyl) methyl carbonodithioate (50, Figure 3.17) were

conducted. We calculated the MM2 strain energy, total energy and potential energy of

minimized structures of xanthates and possible [3, 3], (51) and [3, 5], (52) sigmatropic

rearrangements as shown in Table 3.10. The product from [3, 5] rearrangement, 52 is

more stable than that from the [3, 3] rearrangement, 51 suggesting this might be

observed.


124

50

Figure 3.17: Minimized structure of S-methyl O-phenyl(2-vinylcyclohex-1-

enyl)methyl carbonodithioate (50) where yellow are S-atom, grey are C- atoms, red

are O- atom, pink are lone pair orbitals, and white are H-atoms using MM2 level of

theory.


125


structures of xanthate, 50 and its possible [3, 3], (51) and [3, 5], (52) rearrangement

products using MM2.

Structure Strain

Energy

(kcal/mol)

Total

Energy

(kcal/mol)

Potential

Energy

(kcal/mol)

Total Energy

difference in

rearrangement

(kcal/mol)

Ph

O S

S(CH3)

50

3.87 79.86 43.52 -

Ph

SS(CH3)

O

51

8.52 75.97 41.20 - 3.89

Ph

S

O

S(CH3)

52(E)

2.31 70.07 36.03 - 9.79

Ph

S

O

S(CH3)

52(Z)

3.72 74.56 36.72 -5.30


126

The synthesis of S-methyl O-phenyl (2-vinylcyclohex-1-enyl) methyl carbonodithioate

(50) was attempted from the alcohol, 16 (Scheme 3.20).

Scheme 3.20

3.3.4. Results and Discussion

The synthesis of compound 47 and 50 from the alcohols 18 and 16 respectively

was attempted using NaH, CS2 and CH3I in different ratios with different solvents

THF, DMF and DMSO. But unfortunately, xanthates 47 and 50 were not obtained.

When 47 and 50 are synthesized, a suitable solvent will be chosen so that refluxing in

this solvent will lead to the [3, 3] and [3, 5] rearrangements of these xanthates as

shown in Schemes 3.21 and 3.22.

Scheme 3.21: Proposed rearrangement of S-methyl O-phenyl(2-vinylcyclopent-1-

enyl)methyl carbonodithioate (47)


127

Scheme 3.22: Proposed rearrangement of S-methyl O-phenyl(2-vinylcyclohex-1-

enyl)methyl carbonodithioate (50)

3.4 CONCLUSION

The synthesis of pentadienyl alcohols, 16 and 18 was a key aspect for studying

[3, 3] and [3, 5] rearrangement. These pentadienyl alcohols were further used to

prepare acetate, trichloroacetimidate and methyl carbonodithioate derivatives, in such

a manner that they will form six and eight member transition structure to possibly see

[3, 3] and [3, 5] sigmatropic rearrangements.

The synthesis of phenyl(2-vinyl-cyclopent-1enyl)methyl acetate (25) and

phenyl(2-vinyl-cyclohex-1-enyl)methyl acetate (33) was successful. Later, flash

vacuum pyrolysis was conducted on 25 and 26 to see possible rearrangement products.

The flash vacuum pyrolysis of 25 gave an evidence of [3, 5] rearrangement product

(27). Further, experiments have to be conducted on a larger quantity to confirm the

identity of this product as 27 and to determine, whether the product formed was due to

sequential [3, 3] rearrangement or directly [3, 5] rearrangement. The flash vacuum

pyrolysis of 33 gave β-elimination product (37) which has been purified and

characterized by completely of 1H-NMR and

13C-NMR. It also gave a large amount of


128

starting material (33) with small amount of what appears to be the [3, 5]

rearrangement product (35). Further experiments also need to be conducted on larger

quantity to identify the products formed.

The synthesis of phenyl(2-vinylcyclopent-1-enyl)methyl 2,2,2-

trichloroacetimidate (41) and phenyl(2-vinylcyclohex-1-enyl)methyl 2,2,2-

trichloroacetimidate (44) was successful with the only problem that crude being

unable to be purified. Future experiments for purification of crude to obtain pure

trichloroacetimidates is necessary for studies on possible [3, 3] and [3, 5]

rearrangements.

3.5 EXPERIMENTAL SECTION

General

The 1H NMR,

13C NMR, HMQC and COSY spectra were recorded with a

Varian Unity INOVA 500 FT-NMR (1H NMR at 500 MHz and

13C NMR at 126

MHz) spectrometer. All spectra were obtained in deuterochloroform (CDCl3) with

residual CHCl3 as internal standard unless stated otherwise. Spectra were reported as

follows: chemical shifts (δ) are reported in ppm downfield from TMS and coupling

constants values (J) are in Hz. Infrared (IR) spectra were recorded with a Nicolet

IR100 FT-IR spectrophotometer as deposits from CH2Cl2 solutions on a NaCl plate

unless otherwise stated.

Reagents were purchased from commercial suppliers and used directly unless

otherwise noted. Choloroform (CH3Cl) was dried over CaCl2. Tetrahydrofuran (THF)


129

was dried over sodium with benzophenone as an indicator and distilled immediately

prior to use. Toluene was dried over sodium and distilled immediately before use.

Dimethylformamide (DMF), diethyl ether (Et2O), dichloromethane (DCM) were

purified using a MB-Solvent Purification System. Analytical TLC was performed on

silica gel plates, while silica gel from Sorbent technologies (40-63 µm, 60 Å) was used

for column chromatography.

N-butyllithium (n-BuLi) and tert-butyllithium (t-BuLi) all were titrated to

check the molarity of the bottle. For the titration, in an oven dried round bottom flask,

approximately 0.2 g of L-menthol was weighed and dissolved in solvent used for the

reaction. A pinch of 1,10-phenanthroline was added as indicator. The titration was

carried out under N2. N-butyllithium (n-BuLi) or tert-butyllithium (t-BuLi) was added

slowly using a 1 mL syringe until the color changed from colorless to yellow to a

persistent red. This was done to make sure the equivalents of n-butyllithium (n-BuLi)

and tert-butyllithium (t-BuLi) remain same during the course of experiments.

Synthesis of 2-bromocyclopent-1-ene carbaldehyde (28)43

Br

O

28


130

The following methods were used for synthesis of 2-bromocyclopent-1-ene

carbaldehyde (28). Method A gave a higher yield that method B.

(A) In a 500 mL dry round bottom flask under N2, dry DMF (3.0 eq.,10.96 g, 11.6

mL, 150 mmol) was cooled to 0 ˚C in dry CHCl3 (100 mL) and phosphorous

tribromide, (PBr3, 99% pure, 2.5 eq., 33.8 g, 11.7 mL, 125 mmol) was added

dropwise over a period of 10 min. The mixture was stirred at 0 ˚C for 1 h to

yield a yellow suspension. A solution of cyclopentanone (1.0 eq., 4.2 g, 4.4

mL, 50 mmol) in CHCl3 (10 mL) was added and the mixture was stirred at

room temperature for 12 h. The reaction was cooled to 0 ˚C and aq. NaHCO3

was added slowly until the effervescence subsided. The mixture was extracted

with diethyl ether (3 x 50 mL) and washed with brine (2 x 10 mL). The extract

was dried with MgSO4, concentrated under vacuum and chromatographed on a

silica gel column using 10:1 hexane/ethyl acetate to give a yellow oily product

2-bromocyclopent-1-ene carbaldehyde (28). The identity and purity of the

product was confirmed by TLC, 1H-NMR, HMQC, COSY and

13C-NMR.

Yield: 6.56 g and 75%.

(B) In a 100 mL dry round bottom flask under N2, dry DMF (3.0 eq., 10.96 g, 11.6

mL, 150 mmol) was cooled to 0 ˚C in dry CHCl3 (50 mL) and phosphorous

tribromide (PBr3, 99% pure 2.7 eq., 39.1 g, 13.5 ml, 135 mmol) was added


yield a yellow suspension. A solution of cyclopentanone (1.0 eq., 4.2 g, 4.4

mL, 50 mmol) in CHCl3 (10 mL) was added and the mixture was then refluxed


131

for 60-80 min. The reaction was cooled to 0 ˚C and aq. NaHCO3 was added

slowly until the effervescence subsided. The mixture was extracted with

CH2Cl2 (3 x 50 mL) and washed with brine (2 x 10 mL). The extract was dried

with MgSO4, concentrated under vacuum and chromatographed on a silica gel

column using 10:1 hexane/ethyl acetate to give a yellow oily product 2-

bromocyclopent-1-ene carbaldehyde (28). The identity and purity of the


13C-NMR

(provided in Appendix B, Figure B1, B2, B3 and B4). Yield: 3.94 g and 45%.

Rf = 0.87 (10:1 hexane/ethyl acetate)

1H-NMR (500 MHz, CDCl3, 25°C): δ 1.96-2.1 (m, 2H), 2.47-2.52 (m, 2H),

2.85-2.90 (m, 2H), 9.86 (br s, 1H).

13C-NMR (126 MHz, CDCl3, 25°C): δ 21.3, 29.2, 42.4, 139.9, 141.3, 189.1.

Synthesis of 2-bromocyclohex-1-ene carbaldehyde (37)44

Br

O

37

The following methods were used for synthesis of 2-bromocyclohex-1-ene

carbaldehyde (37). Method B gave a higher yield that method A.

(A) In a 500 mL dry round bottom flask under N2, dry DMF (3.0 eq.,10.96 g, 11.6

mL, 150 mmol) was cooled to 0˚C in dry CHCl3 (100 mL) and phosphorous


132

tribromide, (PBr3, 99% pure 2.5 eq., 33.8 g, 11.7 mL, 125 mmol) was added


yield a yellow suspension. A solution of cyclohexanone (1.0 eq., 4.9 g, 5.2 mL,

50 mmol) in CHCl3 (10 mL) was added and the mixture was stirred at room

temperature for 12 h. The reaction was cooled to 0 ˚C and aq. NaHCO3 was

added slowly until the effervescence subsided. The mixture was extracted with




bromocyclohex-1-ene carbaldehyde (37). The identity and purity of the


13C-NMR.


(B) In a 100 mL dry round bottom flask under N2, dry DMF (3.0 eq., 11.05 g, 11.7

mL, 152.7 mmol) was cooled to 0 ˚C in dry CHCl3 (50 mL) and phosphorus

tribromide, (PBr3, 99% pure 2.7 eq., 39.9 g, 13.8 ml, 137.6 mmol) was added


yield a yellow suspension. A solution of cyclohexanone (1.0 eq., 5.0 g, 5.3 mL,

50.9 mmol) in CHCl3 (10 mL) was added and the mixture was then refluxed

for 60-80 min. The reaction was cooled to 0 ˚C and aq. NaHCO3 was added

slowly until the effervescence subsided. The mixture was extracted with




133


bromocyclohex-1-ene carbaldehyde (37). The identity and purity of the


13C-NMR

(provided in Appendix B, Figure B17, B18, B19 and B20).

Yield: 6.1 g and 65%. Rf = 0.85 (10:1 hexane/ethyl acetate)

1H-NMR (500 MHz, CDCl3, 25°C): δ 1.65-1.78 (m, 4 H), 2.24-2.28 (m, 2H),

2.71-2.76 (m, 2 H), 10.00 (s, 1 H).

13C-NMR (126 MHz, CDCl3, 25°C): δ 21.0, 24.2, 24.9, 38.8, 135.2, 143.6,

193.7.

Synthesis of 1-bromo-2-vinylcyclopentene (29)45

Br

29

The following methods were used for synthesis of 1-bromo-2-vinylcyclopentene (29).

Method B gave a higher yield that method A.

(A) Methyltriphenylphosphonium bromide (1.1 eq., 3.90 g, 11 mmol) was

suspended in THF (15 mL) and n-BuLi (1.1 eq., 6.9 mL, 11 mmol of 1.6 M

solution in hexane) was added dropwise with stirring under N2 at 0 ˚C. It gave

a brown color solution. After 30 min at 0 ˚C, 2-bromocyclopent-1-ene

carbaldehyde (28, 1.0 eq., 1.9 g, 10 mmol) in THF (10 mL) was added


134

dropwise and stirred for 1 h to yield a dark brown color solution. The reaction

was quenched with water (20 mL) and extracted with diethyl ether (3 x 20

mL). The organic layer was washed with brine (2 x 10 mL).The extract was

dried with MgSO4, concentrated under vacuum and chromatographed on a

silica gel column using pentane to give yellow product of 1-bromo-2-

vinylcyclopenetene (29). The identity and purity of the product was confirmed

by TLC, 1H-NMR, HMQC, COSY and

13C-NMR. Yield: 0.92 g and 35%.

(B) In a 250 mL two-necked dry round bottom flask a mixture of

methyltriphenylphosphonium bromide (1.1 eq., 6.0 g, 16.8 mmol) and sodium

amide (NaNH2, 1.7 eq., 1.0 g, 25.6 mmol) was suspended in THF (80 mL)

and stirred under N2 for 60 min at room temperature to yield a bright yellow

color. Then, 2-bromocyclopent-1-ene carbaldehyde (28, 1.0 eq., 2.7 g, 15.2

mmol) in THF (10 mL) was added dropwise and stirred for 90-120 min

yielding a dark brown solution. The reaction was quenched by adding 23 mL

of 25 % aq. NaOH solution. The solution was then neutralized by 31 mL of

0.1 N HCl, extracted with diethyl ether (3 x 20 mL) and washed with brine (2

x 10 mL). The extract was dried with MgSO4, concentrated under vacuum and

chromatographed on a silica gel column using pentane to give yellow oily

product of 1-bromo-2-vinylcyclopenetene (29). The identity and purity of the


13C-NMR

(provided in Appendix B, Figure B5, B6, B7 and B8). Yield: 1.6 g and 60%.

Rf = 0.9 (pentane).


135

1H-NMR (500 MHz, CDCl3, 25 °C): δ 1.94-2.02 (m, 2 H), 2.43-2.49 (m, 2 H),

2.71-2.78 (m, 2 H), 5.17 (dq, J = 14.0, 3.5 Hz, 1 H), 5.22 (dq, J = 10.0, 1.0 Hz,

1 H), 6.62 (dd, J = 10.5, 7.0 Hz, 1 H).

13C-NMR (126 MHz, CDCl3, 25°C): δ 21.4, 30.7, 40.7, 116.8, 120.9, 131.1,

138.2.

IR (neat): 2956.48, 2850.78, 1677.64, 1635.48, 1442.47 cm-1

.

Synthesis of 1-bromo-2-vinylcyclohexene (38)45

Br

38

The following methods were used for synthesis of 1-bromo-2-vinylcyclohexene (38).

Method B gave a higher yield that method A.

(A) Methyltriphenylphosphonium bromide (1.1 eq., 3.90 g, 11 mmol) was

suspended in THF (15 mL) and n-BuLi (1.1 eq., 6.9 mL, 11 mmol of 1.6 M

solution in hexane) was added dropwise with stirring under N2 at 0 ˚C. It gave

a brown color solution. After 30 min at 0 ˚C, 2-bromocyclohex-1-ene

carbaldehyde (37, 1.0 eq., 1.89 g, 10 mmol) in THF (10 mL) was added

dropwise and stirred for 1 h to yield a dark brown color solution. The reaction

was quenched with water (20 mL) and extracted with diethyl ether (3 x 20

mL). The organic layer is washed with brine (2 x 10 mL). The extract was then


136

dried with MgSO4 concentrated under vacuum and chromatographed on a

silica gel column using pentane to give yellow product of 1-bromo-2-

vinylcyclohexene (38). The identity and purity of the product was confirmed

by TLC, 1H-NMR, HMQC, COSY and

13C-NMR. Yield: 0.46 g and 25%.

(B) In a 250 mL two-necked dry round bottom flask a mixture of

methyltriphenylphosphonium bromide (1.1 eq., 3.94 g, 11.03 mmol) and

sodium amide (NaNH2, 1.7 eq., 0.66 g, 16.9 mmol) was suspended in THF (80

mL) and stirred under N2 for 60 min at room temperature to yield a bright

yellow color. Then, 2-bromocyclohex-1-ene carbaldehyde (37, 1.0 eq., 2.0 g,

9.94 mmol) in THF (10 mL) was added dropwise and stirred for 90-120 min

yielding a dark brown solution. The reaction was quenched by adding 23 mL

of 25 % aq. NaOH solution. The solution was then neutralized by 31 mL of 0.1

N HCl, extracted with diethyl ether (3 x 20 mL) and washed with brine (2 x 10

mL). The extract was dried with MgSO4 concentrated under vacuum and

chromatographed on a silica gel column using pentane to give yellow oily

product of 1-bromo-2-vinylcyclohexene (38). The identity and purity of the


13C-NMR



Rf = 0.9 (pentane)


137

1H-NMR (500 MHz, CDCl3, 25°C): δ 1.69-1.74 (m, 4 H), 2.24-2.3 (m, 2 H),

2.6-2.66 (m, 2 H), 5.1 (dq, J = 10.0, 1.0 Hz, 1 H), 5.22 (dq, J = 16.5, 1.0 Hz, 1

H), 6.86 (dd, J = 11.0, 6.5 Hz, 1 H).

13C-NMR (126 MHz, CDCl3, 25°C): δ 22.0, 24.7, 26.7, 37.5, 114.3, 125.1,

132.2, 137.1.

IR (neat): 3434.46, 2934.98, 1629.79, 1435.82 cm-1

.

Synthesis of phenyl(2-vinylcyclopent-1-enyl)methanol (18):46

Ph

OH

18

The following methods were used for synthesis of phenyl(2-vinylcyclopent-1-

enyl)methanol (18). The reaction at -78 ˚C with t-BuLi gave better yield.

(A) A solution of 1-bromo-2-vinylcyclopentene (29, 1.0 eq., 0.152 g, 0.88 mmol)

in 2.7 mL of THF under N2 at -78 ˚C was treated dropwise with n-BuLi (1.1

eq., 1 mL, 0.97 mmol of 1.6 M solution in hexane). After stirring for 15 min

freshly distilled benzaldehyde (1.02 eq., 0.9 mL, 0.90 mmol) was added. After

stirring for 1 h the mixture was allowed to warm to 0 ˚C and quenched with

15 mL of 4% NH4Cl solution. The mixture was extracted with diethyl ether (3

x 35 mL) and organic layer was washed with water and brine. The extract was


138

dried with MgSO4, concentrated under vacuum and chromatographed on a

silica gel column using 6.5:1 hexane/ ethyl acetate to give a yellow product of

phenyl(2-vinylcyclopent-1-enyl)methanol (18). The identity and purity of the


13C-NMR.

Yield: 0.05 g, 30%.

(B) A solution of 1-bromo-2-vinylcyclopentene (29, 1.0 eq., 0.1 g, 0.58 mmol) in

5 mL of dry Et2O under N2 at -78 ˚C was treated dropwise with t-BuLi (1.98

eq., 0.67 mL, 1.15 mmol of 1.7 M solution in pentane) over a period of 15

min. After stirring continuously for 30 min at -78 ˚C, freshly distilled

benzaldehyde (1.03 eq., 0.06 mL, 0.60 mmol) was added. After stirring the

mixture for 5 h at -78 ˚C the cold bath was removed and the mixture was

allowed to slowly attain room temperature and then it was quenched with 15

mL of saturated NH4Cl solution. The mixture was extracted with diethyl ether

(3 x 35 mL) and organic layer was washed with water and brine (2 x 10 mL).

The extract was dried with MgSO4, concentrated under vacuum and

chromatographed on a silica gel column using 10:1 hexane/ ethyl acetate to

give a yellow product of phenyl(2-vinylcyclopent-1-enyl)methanol (18). The

identity and purity of the product was confirmed by TLC, 1H-NMR, HMQC,

COSY and 13

C-NMR (provided in Appendix B, Figure B9, B10, B11 and

B12). Yield: 0.07 g and 60%.

Rf = 0.3 (10:1 hexane/ethyl acetate), 0.55 (5:1 hexane/ethyl acetate).


139

1H-NMR (500 MHz, CDCl3, 25°C): δ 1.73-1.86 (m, 2 H), 1.86 (br s, 1 H),

2.16-2.23 (m, 1 H), 2.52-2.62 (m, 3 H), 5.18 (dd, J = 6.0, 1.0 Hz, 1 H), 5.2

(dd, J = 12.5, 0.5 Hz, 1 H), 5.86 (br, s, 1 H), 6.90 (dd, J = 11.0, 6.0 Hz, 1 H),

7.23-7.40 (m, 5 H);

13C-NMR (126 MHz, CDCl3, 25°C): δ 21.3, 31.8, 32.9, 69.8, 115.4, 125.6,

127.1, 128.3, 130.2, 137.3, 142.1, 142.3.

IR (neat): 3367.7 (O-H) cm-1

.

Synthesis of phenyl(2-vinylcyclohex-1-enyl)methanol (16):46

Ph

OH

16

The following methods were used for synthesis of phenyl(2-vinylcyclohex-1-

enyl)methanol (16). The reaction at -78°C with t-BuLi gave better yields.

(A) A solution of 1-bromo-2-vinylcyclohexene (38, 1.0 eq., 0.165 g, 0.882 mmol)

in 2.7 mL of THF under N2 at -78 ˚C was treated dropwise with n-BuLi (1.1

eq., 1 mL, 0.97 mmol of 1.6 M solution in hexane). After stirring for 15 min

freshly distilled benzaldehyde (1.02 eq., 0.9 mL, 0.90 mmol) was added. After

stirring for 1 h the mixture was allowed to warm to 0 ˚C and quenched with

15 mL of 4% NH4Cl solution. The mixture was extracted with diethyl ether (3


140

x 35 mL) and organic layer was washed with water and brine (2 x 10 mL).


chromatographed on a silica gel column using 6.5:1 hexane/ ethyl acetate to

give a yellow product of phenyl(2-vinylcyclohex-1-enyl)methanol (16). The


COSY and 13

C-NMR. Yield: 0.05 g and 25%.

(B) A solution of 1-bromo-2-vinylcyclohexene, (38, 1.0 eq., 0.1 g, 0.53 mmol) in

5 mL of dry Et2O under N2 at -78 ˚C was treated dropwise with t-BuLi (1.98

eq., 0.62 mL, 1.05 mmol of 1.7 M solution in pentane) over a period of 15

min. After stirring continuously for 30 min at -78 ˚C, freshly distilled

benzaldehyde (1.03 eq., 0.05 mL, 0.50 mmol) was added. After stirring the

mixture for 5 h at -78 ˚C the cold bath was removed and the mixture was

allowed to slowly attain room temperature and then it was quenched with 15

mL of saturated NH4Cl solution. The mixture was extracted with diethyl ether

(3 x 35 mL) and organic layer was washed with water and brine (2 x 10 mL).


chromatographed on a silica gel column using 10:1 hexane/ ethyl acetate to

give a yellow product of phenyl (2-vinylcyclohex-1-enyl) methanol (16). The


COSY and 13

C-NMR (provided in Appendix B, Figure B25, B26, B27 and

B28). Yield: 0.07g and 65%.

Rf = 0.3 (10:1 hexane/ethyl acetate), 0.55 (5:1 hexane/ethyl acetate)


141

1H-NMR (500 MHz, CDCl3, 25°C): δ 1.47-1.78 (m, 5 H), 1.81 (br s, 1 H),

2.20-2.35 (m, 3 H), 5.08 (d, J = 11.0 Hz, 1 H), 5.27 (dd, J = 15.5, 0.5 Hz, 1

H), 6.08 (br, s, 1 H), 7.04 (dd, J = 11.0, 6.5 Hz, 1 H), 7.22-7.38 (m, 5 H).

13C-NMR (126 MHz, CDCl3, 25°C): δ 22.43, 22.45, 23.95, 25.5, 70.7,

113.15, 125.6, 126.8, 128.15, 131.45, 133.8, 137.77, 142.57.

IR (neat): 3596 (O-H) cm-1

.

Synthesis of phenyl (2-vinylcyclopent-1enyl) methyl acetate (25):47

Ph

O

O

25

In a 25 mL round bottom flask, a solution of phenyl(2-vinylcyclopent-1-

enyl)methanol (18, 1.0 eq., 0.12 g, 0.6 mmol) dissolved in 5 mL of DCM

under N2 at 0 °C was treated with acetyl chloride, (CH3COCl, 1.05 eq., 0.05

mL, 0.05 g, 0.63 mmol). After stirring the reaction mixture at 0 °C for 15 min

pyridine (1.05 eq., 0.05 mL, 0.05 g, 0.63 mmol) was added to remove HCl

produced during the reaction. The reaction was stirred at room temperature for

24 h. The reaction was the quenched with 10 mL of water. The mixture was

extracted with DCM (3 x 15 mL) and organic layer was washed with water

and brine (2 x 5 mL). The extract was dried with MgSO4, concentrated under


142

vacuum and chromatographed on a silica gel column using 10:1 hexane/ ethyl

acetate to give a yellow oily product of phenyl (2-vinylcyclopent-1enyl)

methyl acetate (25). The identity and purity of the product was confirmed by

TLC, 1H-NMR, HMQC, COSY and

13C-NMR (provided in Appendix B,

Figure B13, B14, B15 and B16). Yield: 0.13 g and 86%.

Rf = 0.7 (10:1 hexane/ ethyl acetate)

1H-NMR (500 MHz, CDCl3, 25°C): δ 1.75-1.88 (m, 2 H), 2.14 (br, s, 3 H),

2.25-2.33 (m, 1 H), 2.52-2.58 (m, 3 H), 5.2 (d, J = 3.0 Hz, 1 H), 5.23 (d, J =

0.5 Hz, 1 H), 6.86 (br, s, 1 H), 6.96 (dd, J = 10.5, 7.5 Hz, 1 H), 7.24-7.36 (m,

5 H).

13C-NMR (126 MHz, CDCl3, 25°C): δ 21.13, 21.16, 32.56, 32.69, 71.58,

116.0, 125.9, 128.34, 130.16, 130.25, 138.1, 138.5, 139.0, 169.96.

IR (neat): 1737 (C=O) cm-1

.

Synthesis of phenyl(2-vinylcyclohex-1enyl)methyl acetate (33):47

Ph

O

O

33


143

In a 25 mL round bottom flask, a solution of phenyl(2-vinylcyclohex-1-

enyl)methanol (16, 1.0 eq., 0.2 g, 0.9 mmol) dissolved in 5 mL of DCM

under N2 at 0 °C was treated with acetyl chloride, (CH3COCl, 1.05 eq., 0.07

mL, 0.07 g, 0.94 mmol). After stirring the reaction mixture at 0 °C for 15

min pyridine (1.05 eq., 0.08 mL, 0.07 g, 0.94 mmol) was added to remove

HCl produced during the reaction. The reaction was stirred at room

temperature for 24 h. The reaction was the quenched with 10 mL of water.

The mixture was extracted with DCM (3 x 15 mL) and organic layer was

washed with water and brine (2 x 5 mL). The extract was dried with MgSO4,

concentrated under vacuum and chromatographed on a silica gel column

using 10:1 hexane/ ethyl acetate to give a yellow oily product of phenyl (2-

vinylcyclohex-1enyl) methyl acetate (33). The identity and purity of the


13C-NMR

(provided in Appendix B, Figure B29, B30, B31 and B32). Yield: 0.16 g and

68%.

Rf = 0.7 (10:1 hexane/ ethyl acetate)

1H-NMR (500 MHz, CDCl3, 25 °C): δ 1.48-1.71 (m, 5 H), 1.8-1.9 (m, 1 H),

2.17 (br, s, 3 H), 2.20-2.36 (m, 2 H), 5.12 (d, J = 11.0 Hz, 1 H), 5.28 (dd, J =

16.5, 0.5 Hz, 1 H), 7.08 (br, s, 1 H), 7.12 (dd, J = 11.0 Hz, 1 H), 7.24-7.35 (m,

5 H).

13C-NMR (126 MHz, CDCl3, 25°C): δ 21.13, 22.26, 22.34, 24.69, 25.42,

72.86, 113.57, 125.7, 127.21, 128.24, 132.62, 133.96, 134.03, 139.41, 170.03.


144

IR (neat): 1741.18 (C=O) cm-1

.

Flash Vacuum Pyrolysis of 33 and synthesis of 1-((1E)-(2-vinylcyclohex-2-

enylidene)methylbenzene (37):

Ph

37

Approximately 100-200 mg of 33 was dissolved in anhydrous diethyl ether

(because it is very viscous, it needed to be diluted for transfer) was placed in

the quartz tube. A vacuum of 0.1 torr was drawn on the quartz tube to remove

residual solvents such as diethyl ether, hexane or ethyl acetate. Then the

equipment was set up as shown in Figure 3.9. The liquid nitrogen bath is kept

under the U-tube to cool the pyrolysates. The pyrolysis oven was adjusted to a

proper temperature and the digital thermometer was set in the middle of the

oven to read the temperature of the oven. After the oven had reached a

required temperature, the closed end of the quartz tube was slowly pushed

inside the oven. This was continued until the closed end of the tube had gone

inside the oven and the sample had vaporized the quartz tube. The products

were collected either at the end of the end of quartz tube or in the U-tube.

After the pyrolysis tube cooled, the system was filled with nitrogen. The U-

tube was removed from the system and warmed up to room temperature. A


145

1H-NMR spectrum was obtained for crude the pyrolysis products collected

both at the end of the pyrolysis tube and in the U-tube. The sample obtained

was then chromatographed on silica gel column using 2% ethyl acetate in

hexane solution to separate the different products. The identity and purity of

the product was confirmed by TLC, 1H-NMR, HMQC, COSY and

13C-NMR


Rf = 0.85 (2% ethyl acetate in hexane).

1H-NMR (500 MHz, CDCl3, 25°C): δ 1.65-1.71 (m, 2 H), 2.24-2.3 (m, 2 H),

2.6-2.64 (m, 2 H), 5.1 (dd, J = 8.5, 2.0 Hz, 1 H), 5.38 (dd, J = 15.0, 2.0 Hz, 1

H), 6.02 (t, J = 4.0, Hz, 1 H), 6.5 (br, s, 1 H), 6.53 (dd, J = 11.0, 5.0 Hz, 1 H),

7.2-7.4 (m, 5 H).

13C-NMR (126 MHz, CDCl3, 25°C): δ 22.38, 26.24, 26.96, 115.09, 124.34,

126.14, 127.98, 128.77, 129.24, 137.11, 137.22, 138.03, 138.31.

Synthesis of phenyl(2-vinylcyclopent-1-enyl)methyl 2,2,2-trichloroacetimidate

(41):48

Ph

O

NH

CCl3

41


146

Various procedures were tried for synthesis of phenyl(2-vinylcyclopent-1-

enyl)methyl 2,2,2-trichloroacetimidate (41):

(a) NaH (0.1 eq., 0.042 mmol, 1.7 mg of 60% dispersion in mineral oil) was

washed with hexane, suspended in absolute diethyl ether (2 mL) and cooled to

0 °C. Phenyl(2-vinylcyclopent-1-enyl)methanol (18, 1.0 eq., 85 mg, 0.42

mmol) dissolved in diethyl ether (1 mL) was added. After the reaction time 20

min, the reaction mixture was cooled to 0 °C and trichloroacetonitrile (1.05

eq., 0.44 mmol, 0.06 g, 40 µL) was added. The reaction was monitored by

TLC and 1H-NMR. The reaction was monitored for 3 days and no new

product could be seen. Hence, it was concluded that the reaction did not work

with NaH as base.

(b) A suspension of potassium hydride (0.2 eq. 5 mg, 0.034 mmol of a 30%

dispersion in mineral oil), washed twice with hexane was suspended in 2 mL

of diethyl ether was cooled to 0 °C. Phenyl(2-vinylcyclopent-1-enyl)methanol

(18, 1.0 eq., 35 mg, 0.17 mmol) dissolved in 1 mL of diethyl ether was added

to it. After 20 min trichloroacetonitrile (1.2 eq., 0.20 mmol, 0.03 g, 0.02 mL)

was added at 0 °C to the reaction. The reaction mixture was then let to stir

initially for 2 h at 0 °C and then at the room temperature. The reaction was

monitored by TLC and 1H-NMR. The reaction was monitored for 12 h and no

new product formed could be seen. Hence, it was concluded that the reaction

did not work with KH as base.


147

(c) To phenyl(2-vinylcyclopent-1-enyl)methanol (18, 1.0 eq., 0.21 g, 1.04 mmol),

2 mL of dicholoromethane was added. The mixture was kept under N2 at 0

°C, and 1,8 diazabicycloundec-7-ene (DBU) (0.1 eq., 15 µL, 0.1 mmol) was

added. The solution was stirred for 15 min at 0 °C and trichloroacetonitrile

(5.0 eq., 52 µL, 5.2 mmol) was added and stirred for 1 h. A crude NMR taken

after 1 h showed phenyl(2-vinylcyclopent-1-enyl)methyl 2,2,2-

trichloroacetimidate (41). The solvent was not removed and the crude was

directly loaded on column to be purified by flash chromatography using 2%

ethyl acetate solution in hexane. The problem was that the phenyl(2-

vinylcyclopent-1-enyl)methyl 2,2,2-trichloroacetimidate (41) rearranged on

silica gel to give product 42.

Crude 1H-NMR (300 MHz, CD2Cl2, 25°C) tentatively assigned to 41:

1H-

NMR : δ 1.4-1.6 (m, 5 H), 2.10-2.4 (m, 3 H), 5.31 (dd, 1 H), 5.35 (dd, 1 H),

7.08 (br, s, 1 H), 7.12 (dd, 1 H), 7.3-7.6 (m, 5 H), 8.6 (br, s, 1H).

1H-NMR (500 MHz, CDCl3, 25°C) tentatively assigned to 42: δ 1.79-1.88 (m,

5 H), 1.98-2.08 (m, 3 H), 5.22 (dd, 9, 1.5 Hz, 1 H), 5.43 (dd, 16.0, 1.5 Hz, 1

H), 5.94 (dd, 10.5, 7.0 Hz, 1 H), 6.54 (br, s, 1H), 7.28 (br, s, 1 H), 7.3-7.4 (m,

5 H).


148

Synthesis of phenyl(2-vinylcyclohex-1-enyl)methyl 2,2,2-trichloroacetimidate (44):48

Ph

O

NH

CCl3

44

Various procedures were tried for synthesis of compound 44:

(a) NaH (0.1 eq., 0.042 mmol, 1.7 mg 60% dispersion in mineral oil) was

washed with hexane, then suspended in absolute diethyl ether (2 mL) and

cooled to 0 °C. Phenyl(2-vinylcyclohex-1-enyl)methanol (16, 1.0 eq., 84 mg,

0.42 mmol) dissolved in diethyl ether (1 mL) was added. After the reaction

time 20 min, the reaction mixture was cooled to 0 °C and trichloroacetonitrile

(1.05 eq., 0.44 mmol, 0.06 g, 40 µL) was added. The reaction was monitored

by TLC and 1H-NMR. The reaction was monitored for 3 days and no new

product could be seen. Hence, it was concluded that the reaction did not work

with NaH as base.

(b) A suspension of potassium hydride (0.2 eq. 5 mg, 0.034 mmol of a 30%

dispersion in mineral oil), washed twice with hexane was suspended in 2 mL

of diethyl ether was cooled to 0 °C. Phenyl(2-vinylcyclohex-1-enyl)methanol,

(16, 1.0 eq., 34 mg, 0.17 mmol) dissolved in 1mL of diethyl ether was added

to it. After 20 min trichloroacetonitrile (1.2 eq., 0.20 mmol, 0.03 g, 0.02 mL)

was added at 0 °C to the reaction. The reaction mixture was then let to stir


149

initially for 2 h at 0 °C and then at the room temperature. The reaction was

monitored by TLC and 1H-NMR. The reaction was monitored for 12 h and no

new product formed could be seen. Hence, it was concluded that the reaction

did not work with KH as base.

(c) To phenyl(2-vinylcyclohex-1-enyl) methanol (16, 1.0 eq., 0.27 g, 1.24 mmol),

2 mL of dicholoromethane was added. The mixture was kept under N2 at 0

°C, and 1,8 diazabicycloundec-7-ene (DBU) (0.1 eq., 18 µL, 0.12 mmol) was

added. The solution was stirred for 15 min at 0 °C and trichloroacetonitrile

(5.0 eq., 62 µL, 6.2 mmol) was added and stirred for 1 h. A crude NMR taken

after 1 h showed phenyl(2-vinylcyclohex-1-enyl)methyl 2,2,2-

trichloroacetimidate (44). The solvent was not removed and the crude was

directly loaded on column to be purified by flash chromatography using 2%

ethyl acetate solution in hexane. The problem was that the phenyl(2-

vinylcyclohex-1-enyl)methyl 2,2,2-trichloroacetimidate (44) rearranged on

silica gel to give product 45 and some amount of 44 (1H-NMR in Appendix

B).

Crude 1H-NMR (300 MHz, CDCl3, 25°C) tentatively assigned to 44:

1H-

NMR : δ 1.75-1.99 (m, 5 H), 2.33-2.5 (m, 3 H), 5.0 (dd, 1 H), 5.15 (dd, 1 H),

7.01 (br, s, 1 H), 7.2 (dd, 1 H), 7.3-7.6 (m, 5 H), 8.3 (br, s, 1H).


150

Attempted synthesis of S-methyl O-phenyl(2-vinylcyclopent-1-enyl)methyl

carbonodithioate (47):49

O

Ph S

S(CH3)

47


(a) To a stirred solution of phenyl(2-vinylcyclopent-1-enyl)methanol (18, 1.0 eq.,

0.12g, 0.62 mmol) in THF at 0 °C, CS2 (67.17 eq., 2.6 mL, 41.6 mmol) was

added, followed by CH3I (67.5 eq., 2.7 mL, 41.8 mmol). After stirring for 15 min

NaH (2.1 eq., 0.05 g of 60% dispersion in mineral oil) was added slowly and the

reaction mixture was stirred at 0 °C for 20 min. The reaction mixture was then

quenched with ice and organic layer was extracted with ethyl acetate. The

organic layer was then washed with brine, dried over MgSO4 and concentrated in

vacuum to give yellow oil. The reaction was monitored by TLC and it showed a

lot of new spots with possibility of product 47. 1H-NMR of crude showed peaks

corresponding to 47. But the crude compound 47 seemed to decompose on the

silica gel column.

(b) A stirred solution of phenyl(2-vinylcyclopent-1-enyl)methanol (18, 1.0 eq., 0.1

g, 0.5 mmol) in THF, NaH (1.2 eq., 30 mg of 60% dispersion in mineral oil) was

added slowly portionwise at 0 °C. After the resulting mixture was stirred for 1 h

at room temperature, CS2 (2 eq., 70 µL) was added dropwise at 0 °C. The

resultant mixture was stirred for 2 h at room temperature before CH3I (1.2 eq.,


151

40 µL) was added dropwise to the reaction mixture at 0 °C. The resultant

mixture was stirred for 1 h at room temperature, treated with NH4Cl solution and

extracted with diethyl ether. The organic layer was washed with brine, dried over

MgSO4 and concentrated under vacuum. The reaction was monitored by TLC

and it showed a lot of new spots with possibility of product 47. 1H-NMR of

crude showed peaks corresponding to 47. But the crude compound 47 seemed to

decompose on the silica gel column.

(c) DMSO (2 mL) was added under N2 to NaH (1.2 eq., 40 mg of 60% dispersion in

mineral oil) and the mixture was heated to 70 °C and stirred for 45 min. After

cooling the reaction mixture phenyl(2-vinylcyclopent-1-enyl)methanol (18, 1.0

eq., 0.12 g, 0.6 mmol) dissolved in 1 mL of DMSO was added dropwise and the

mixture was stirred at room temperature for 1 h. A solution of CS2 (1.2 eq., 0.04

mL) was added slowly. After 1 h stirring at room temperature a solution of CH3I

(1.2 eq., 0.05 mL) was added. The reaction mixture was stirred for 1 h at room

temperature. It was quenched with ice, the organic layer was extracted with

hexane and washed with water to remove DMSO. 1H-NMR of crude showed

peaks corresponding to 18 only. Hence, no reaction occurred.

(d) To a stirred solution of phenyl (2-vinylcyclopent-1-enyl) methanol, (18) (1.0 eq.,

68 mg, 0.34 mmol) in DMF, NaH (1.2 eq., 16 mg of 60% dispersion in mineral

oil) was slowly added portionwise at 0 °C. After the resulting mixture was stirred

for 1h at room temperature CS2 (2 eq., 0.04 mL) was added dropwise at 0 °C.

The resulting mixture was stirred for 2 h at room temperature before CH3I (1.2


152

eq., 0.03 mL) was added to the reaction mixture at 0 °C. The resulting mixture

was stirred for 1 h at room temperature, quenched with NH4Cl and extracted

with ether. The combined layer was washed with brine, dried over MgSO4 and

concentrated under vacuum. 1H-NMR of crude showed peaks corresponding to

18 only. Hence, no reaction occurred.

Attempted synthesis of S-methyl O-phenyl (2-vinylcyclohex-1-enyl) methyl

carbonodithioate (50):49

Ph

O

S

S(CH3)

50


(a) To a stirred solution of phenyl(2-vinylcyclohex-1-enyl)methanol (16, 1.0 eq.,

0.13 g, 0.62 mmol) in THF at 0 °C, CS2 (67.17 eq., 2.6 mL, 41.6 mmol) was

added, followed by CH3I (67.5 eq., 2.7 mL, 41.8 mmol). After stirring for 15 min

NaH (2.1 eq., 0.05 g of 60% dispersion in mineral oil) was added slowly and the

reaction mixture was stirred at 0 °C for 20 min. The reaction mixture was then

quenched with ice and organic layer was extracted with ethyl acetate. The

organic layer was then washed with brine, dried over MgSO4 and concentrated in

vacuum to give yellow oil. The reaction was monitored by TLC and it showed a

lot of new spots with possibility of product 50. 1H-NMR of crude showed peaks


153

corresponding to 50. But the crude compound 50 seemed to decompose on the

silica gel column.

(b) A stirred solution of phenyl(2-vinylcyclohex-1-enyl)methanol, (16, 1.0 eq., 107

mg, 0.5 mmol) in THF, NaH (1.2 eq., 30 mg of 60% dispersion in mineral oil)

was added slowly portionwise at 0 °C. After the resulting mixture was stirred for

1 h at room temperature, CS2 (2 eq., 70 µL) was added dropwise at 0 °C. The

resultant mixture was stirred for 2 h at room temperature before CH3I (1.2 eq.,

40 µL) was added dropwise to the reaction mixture at 0 °C. The resultant

mixture was stirred for 1 h at room temperature, treated with NH4Cl solution and

extracted with diethyl ether. The organic layer was washed with brine, dried over

MgSO4 and concentrated under vacuum. The reaction was monitored by TLC

and it showed a lot of new spots with possibility of product 50. 1H-NMR of

crude showed peaks corresponding to 50. But the crude compound 50 seemed to

decompose on the silica gel column.

(c) DMSO (2 mL) was added under N2 to NaH (1.2 eq., 40 mg of 60% dispersion in

mineral oil) and the mixture was heated to 70 °C and stirred for 45 min. After

cooling the reaction mixture phenyl(2-vinylcyclohex-1-enyl)methanol (16, 1.0

eq., 128 mg, 0.6 mmol) dissolved in 1 mL of DMSO was added dropwise and

the mixture was stirred at room temperature for 1 h. A solution of CS2 (1.2 eq.,

0.04 mL) was added slowly. After 1 h stirring at room temperature a solution of

CH3I (1.2 eq., 0.05 mL) was added. The reaction mixture was stirred for 1 h at

room temperature. It was quenched with ice, the organic layer was extracted with


154

hexane and washed with water to remove DMSO. 1H-NMR of crude showed

peaks corresponding to 16 only. Hence, no reaction occurred.

(d) To a stirred solution of phenyl(2-vinylcyclohext-1-enyl)methanol (16, 1.0 eq., 73

mg, 0.34 mmol) in DMF, NaH (1.2 eq., 16 mg of 60% dispersion in mineral oil)

was slowly added portionwise at 0 °C. After the resulting mixture was stirred for

1 h at room temperature CS2 (2 eq., 0.04 mL) was added dropwise at 0°C. The

resulting mixture was stirred for 2 h at room temperature before CH3I (1.2 eq.,

0.03 mL) was added to the reaction mixture at 0 °C. The resulting mixture was

stirred for 1 h at room temperature, quenched with NH4Cl and extracted with

ether. The combined layer was washed with brine, dried over MgSO4 and

concentrated under vacuum. 1H-NMR of crude showed peaks corresponding to

16 only. Hence, no reaction occurred.


155

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161

APPENDIX- A

OPTIMIZED CARTESIAN COORDINATES FOR THE

THEORETICAL CALCULATIONS


162

Cartesian coordinates of all stationary structures at different levels.

[3, 3] sigmatropic rearrangement of allyl azide

Ground State (1a)

RB3LYP/6-31G(d,p)

C .000007825 .000031819 -.000011125

C -.000023219 -.000021619 .000021816

C .000011083 .000007571 -.000005048

H .000009121 .000008845 .000003558

N .000007902 -.000054733 -.000045079

N .000073161 .000091318 .000106815

N -.000088452 -.000047665 -.000058837

H .000007271 -.000004969 -.000004827

H -.000003695 -.000017648 .000010074

H -.000006222 -.000001610 -.000006182

H .000005225 .000008692 -.000011166

RHF/6-31G(d,p)

C -.000018963 .000000395 .000003138

C .000013176 -.000018412 .000001521

C -.000006899 .000011309 -.000005845

H -.000005075 -.000013608 .000002187


163

N .000005530 -.000008907 .000016253

N .000004840 .000009748 -.000024945

N .000013467 .000010419 .000012447

H .000001659 .000003068 -.000011412

H .000001339 .000002279 -.000011051

H -.000007725 .000006071 .000005640

H -.000001350 -.000002360 .000012067

RMP2/6-31G(d,p)

C .000002496 -.000000534 -.000003577

C -.000000414 .000001805 .000005703

C -.000000131 -.000000155 -.000001046

H -.000000168 .000000512 .000000079

N .000000245 -.000002414 -.000002691

N -.000003962 -.000002365 .000004704

N .000002262 .000003732 -.000002230

H .000000839 -.000001076 -.000000477

H -.000000482 .000000251 -.000000836

H .000000483 -.000000094 -.000000005

H -.000001168 .000000337 .000000376

Transition State (5)


164

RB3LYP/6-31G(d,p)

C -.000003285 -.000000932 -.000005096

C .000005653 -.000015573 -.000016632

C .000009082 .000010114 .000016232

H .000006285 -.000003389 -.000001846

N .000009904 .000006192 .000022783

N -.000035941 .000012466 .000013989

N -.000015299 .000000267 -.000021678

H .000006430 -.000003054 -.000004094

H .000009053 .000000721 -.000003570

H .000007738 -.000006903 .000000117

H .000000380 .000000091 -.000000206

RHF/6-31G(d,p)

C .000004464 .000006282 .000004293

C -.000015589 -.000000017 -.000006634

C .000004422 -.000006270 .000004287

H -.000001725 .000000329 -.000003862

N .000019022 -.000078491 -.000007670

N -.000028714 -.000000091 .000013795

N .000019041 .000078586 -.000007678

H -.000002500 -.000000547 .000005372

H -.000002485 .000000546 .000005370

H -.000001720 -.000000323 -.000003858

H .000005784 -.000000003 -.000003413


165

RMP2/6-31G(d,p)

C -.000006334 .000004339 -.000007043

C .000003742 .000000026 .000006696

C -.000006334 -.000004309 -.000007056

H -.000000228 -.000002901 .000001535

N -.000003108 -.000059956 .000010337

N .000022656 .000000049 -.000012791

N -.000003088 .000059908 .000010353

H -.000002954 .000000602 -.000001021

H -.000002967 -.000000608 -.000000995

H -.000000228 .000002858 .000001510

H -.000001157 -.000000008 -.000001526

Conformation-1 (1b)

RB3LYP/6-31G(d,p)

C -.000001631 -.000000222 -.000005062

C .000003760 .000005662 -.000006258

C -.000001764 -.000002632 .000003864

H .000000807 .000000876 .000001079

H -.000000388 -.000000160 -.000001120

H .000000188 .000000090 -.000001312

H .000001453 -.000001234 -.000000324

H .000000867 -.000000777 .000000660


166

N -.000005700 .000012805 .000011073

N .000005179 -.000021603 -.000008463

N -.000002771 .000007194 .000005863

RHF/6-31G(d,p)

C -.000011729 .000001045 -.000012583

C -.000005051 -.000001425 .000003420

C .000001256 .000004138 .000000008

C -.000002210 .000003881 .000004030

H -.000001182 .000000711 -.000001398

H -.000000253 -.000000317 -.000000190

H .000000815 -.000000221 .000000484

H .000003638 -.000008620 -.000001232

N .000022904 .000014945 .000016445

N .000104130 -.000003252 -.000019310

N -.000112319 -.000010886 .000010325

RMP2/6-31G(d,p)

C -.000004021 -.000043240 -.000000800

C -.000001027 -.000023241 .000000365

C .000013418 .000038927 -.000000183

H -.000001389 .000021642 -.000000131

H -.000001367 .000011454 .000000047

H -.000008702 -.000009448 .000000244

H .000009534 -.000011983 -.000000276

H -.000000374 .000022113 .000000394

N -.000040706 .000000096 -.000001002


167

N -.000049888 -.000015609 .000001792

N .000084521 .000009290 -.000000450

Conformation-2 (1c)

RB3LYP/6-31G(d,p)

C -.000001593 .000002730 -.000000646

C -.000000712 .000000147 .000000903

C .000000503 .000001874 -.000000175

H -.000006523 .000004244 .000000376

H .000000150 .000003660 .000001690

H .000001063 .000000975 .000000139

H -.000000102 -.000002859 -.000001049

H .000002281 .000004303 .000001925

N .000001116 -.000004518 .000004802

N -.000000162 -.000004871 -.000004787

N .000003978 -.000005684 -.000003179

RHF/6-31G(d,p)

C .000001582 -.000000126 -.000000610

C .000000521 -.000000003 .000000117

C -.000000186 .000000019 -.000000208

H -.000000120 .000000183 .000000234

H .000000375 .000000068 .000000087


168

H .000000150 -.000000106 -.000000041

H -.000000269 -.000000164 -.000000042

H -.000000512 .000000140 -.000000066

N -.000000650 -.000002617 .000001561

N .000002655 .000009424 -.000000341

N -.000003546 -.000006818 -.000000689

RMP2/6-31G(d,p)

C -.000007848 -.000003080 .000000718

C -.000000928 -.000011874 .000002265

C .000003191 .000003980 -.000004262

H -.000004419 -.000000679 .000001539

H .000001967 .000001401 -.000000727

H .000001221 -.000001034 .000000150

H .000000768 -.000000091 .000001121

H .000000255 .000000690 -.000001753

N -.000007010 -.000005184 -.000001887

N -.000014447 -.000006396 -.000013634

N .000027251 .000022268 .000016470

Conformation-3(1d)

RB3LYP/6-31G(d,p)

C -.000001393 -.000003541 .000000992


169

C -.000000244 .000000966 -.000001671

C .000000138 .000003154 -.000000809

H .000000068 -.000002422 .000000816

N -.000000257 -.000000819 -.000000375

N -.000000214 -.000002371 .000000448

N .000000141 -.000003827 .000001552

H .000002388 .000001149 .000002453

H .000001889 .000003892 .000001164

H -.000000469 .000003654 -.000001718

H -.000002046 .000000165 -.000002853

RHF/6-31G(d,p)

C -.000003177 .000000361 .000003723

C .000001135 -.000000622 .000001099

C -.000002092 .000000234 -.000001882

H .000000057 .000000058 .000000789

N .000000797 -.000006193 -.000008157

N -.000018936 .000001137 .000004341

N .000023481 .000003161 -.000000347

H .000000145 .000001041 -.000000617

H -.000000152 .000000947 -.000000294

H -.000000916 -.000000347 -.000000120

H -.000000342 .000000222 .000001464

RMP2/6-31G(d,p)

C -.000003291 -.000004162 .000000224

C .000005311 .000004942 -.000003785


170

C .000003018 -.000000763 .000001635

H -.000002084 -.000000620 .000000745

N -.000006708 -.000005543 .000003945

N .000001684 .000004165 -.000004743

N .000001881 -.000000562 .000001862

H -.000000792 .000002936 -.000000160

H .000000035 -.000000629 -.000000517

H -.000000643 .000000494 .000000987

H .000001589 -.000000257 -.000000192

Conformation-4 (1e)

RB3LYP/6-31G(d,p)

C .000001463 -.000006503 .000005438

C -.000008526 .000005652 -.000018073

C .000003075 -.000000654 -.000003079

H -.000004530 -.000006653 .000004872

N -.000036873 .000006056 .000006482

N .000077069 -.000007723 .000004639

N -.000017876 .000000440 .000001465

H -.000016289 .000008997 .000000362

H .000001141 -.000001730 -.000001247

H .000001634 .000002096 -.000001394

H -.000000289 .000000022 .000000535


171

RHF/6-31G(d,p)

C .000012551 .000001422 .000007363

C -.000004358 -.000000708 -.000004788

C .000003089 -.000001818 .000003845

H -.000006281 .000001585 -.000001202

N -.000001075 .000005267 .000005879

N -.000019758 -.000001352 -.000022407

N .000007577 .000000102 .000013841

H .000006279 -.000005682 -.000001985

H .000001780 -.000003621 .000000740

H .000002414 .000002985 -.000000550

H -.000002217 .000001820 -.000000736

RMP2/6-31G(d,p)

C .000041664 .000002617 .000005972

C -.000031409 .000006115 -.000025275

C .000033288 -.000011550 .000013660

H .000000148 -.000001498 .000014477

N -.000000117 .000006758 -.000000474

N .000007245 -.000077342 .000006538

N -.000073174 .000087796 -.000002371

H .000026230 .000001138 -.000010963

H -.000007200 .000008284 -.000001909

H -.000008789 -.000007755 -.000003020

H .000012115 -.000014563 .000003365


172

[3, 5] sigmatropic rearrangement of vinylogous azides

Transition State-1 (11)

RB3LYP/6-31G(d,p)

C .000001173 .000006054 .000016174

C .000001624 .000004940 .000031247

C -.000027766 -.000003505 -.000041885

C -.000040782 .000031350 .000084463

H .000000383 -.000006324 -.000021363

H .000002032 .000002101 .000004346

H -.000008512 .000003676 .000013003

H .000009233 -.000009695 -.000038420

C -.000022318 -.000012471 -.000005860

H .000002505 -.000012667 -.000005567

N .000044725 -.000002153 -.000006192

N -.000006347 .000012303 .000002862

N .000039729 -.000011202 -.000034944

H .000000958 .000002207 -.000011526

H .000003364 -.000004615 .000013662


173

RHF/6-31G(d,p)

C .000007589 .000008583 -.000006649

C -.000008850 .000001670 -.000007674

C .000005043 -.000002074 .000001248

C -.000003095 -.000001488 .000003318

H -.000002936 .000003745 .000003372

H .000001233 -.000002243 -.000003941

H -.000000011 -.000000376 -.000001549

H .000001452 .000000062 .000001591

C .000001587 -.000016823 .000005871

H -.000002148 .000001423 .000001610

N .000004309 .000001734 -.000002056

N -.000004633 -.000003905 -.000006104

N .000001187 .000002805 .000002918

H -.000000662 .000002122 .000003548

H -.000000065 .000004765 .000004497

RMP2/6-31G(d,p)

C .000012079 .000016086 .000003737

C -.000014496 .000007669 .000003501

C .000003060 .000013824 .000017346

C .000002850 -.000005907 -.000010394

H -.000002433 .000001973 .000004165

H -.000001249 -.000002847 -.000000979

H .000000804 .000000607 -.000004265

H .000003619 .000005776 .000007578


174

C -.000001609 .000006651 -.000022239

H .000001230 -.000000831 -.000002811

N .000013329 -.000023154 .000002695

N -.000042607 -.000022037 .000000124

N .000017318 .000005572 .000014105

H .000000042 -.000000182 .000000208

H .000008064 -.000003201 -.000012771

Reactant-1 (12)

RB3LYP/6-31G(d,p)

C .000013321 .000003049 .000007617

C -.000008647 -.000008727 .000005859

C -.000002898 -.000012129 .000003074

C -.000011760 -.000014219 .000008967

H .000001346 .000002964 .000002562

H -.000000944 -.000001116 .000002272

H .000008364 .000000036 -.000003741

H -.000001013 -.000004567 -.000001411

C -.000015906 .000009963 -.000004642

H -.000001111 .000005836 -.000000580

N .000020183 -.000001818 -.000024242

N -.000028960 -.000008778 .000020818


175

N .000031225 .000027310 -.000012447

H -.000002131 -.000003142 -.000001790

H -.000001068 .000005339 -.000002317

RHF/6-31G(d,p)

C .000006044 -.000037575 -.000002823

C -.000016752 -.000003519 -.000001541

C .000015153 .000005436 -.000000472

C .000008954 -.000015232 -.000006242

H -.000001174 -.000003428 -.000002857

H -.000000981 -.000002196 .000001274

H -.000000755 -.000000148 -.000002975

H .000002005 -.000000059 -.000000217

C -.000007189 .000003439 .000004706

H -.000002785 .000000204 -.000001248

N -.000019645 .000013558 -.000020021

N .000048707 .000021024 .000021821

N -.000033770 .000019525 .000008526

H .000002338 -.000001429 .000000216

H -.000000149 .000000400 .000001852

RMP2/6-31G(d,p)

C -.000010130 -.000012737 .000019121

C -.000019220 -.000010378 -.000012668

C .000013486 -.000003136 -.000016953

C .000027764 .000001240 .000006605

H .000005833 .000006168 -.000000651


176

H -.000000724 .000006898 .000004240

H .000004533 .000002972 .000008409

H -.000001336 -.000000666 .000000870

C .000000299 -.000002889 .000004613

H .000004567 -.000000478 -.000000372

N -.000019577 .000008323 -.000006791

N -.000063854 .000011894 .000005242

N .000060526 -.000014819 -.000013548

H -.000002658 .000007036 .000004265

H .000000492 .000000572 -.000002382

Product-1 (13)

RB3LYP/6-31G(d,p)

C .000004156 -.000001371 -.000004003

C -.000000516 -.000002147 -.000004044

C -.000003226 -.000000768 -.000000278

C -.000001418 .000001264 .000003008

H .000006228 -.000002535 -.000006061

H -.000001485 -.000003347 -.000006847

H -.000001759 .000002083 .000004693

H .000001809 .000002115 .000003481

C .000004932 -.000000735 -.000001767

H .000008355 -.000000506 -.000002095


177

N -.000004930 .000001990 .000004558

N -.000004498 .000002104 .000004850

N -.000004640 .000002888 .000005788

H -.000005847 -.000000928 -.000001466

H .000002839 -.000000107 .000000182

RHF/6-31G(d,p)

C .000003315 -.000002516 -.000004219

C .000001378 -.000000895 .000000928

C .000000446 -.000000476 -.000002109

C .000000825 .000002043 -.000000253

H -.000001180 -.000000510 -.000001113

H -.000000137 .000001130 .000001937

H -.000001355 .000002724 -.000001682

H .000001144 .000000108 .000000798

C -.000003382 .000004640 .000002577

H .000000006 -.000001111 -.000000619

N -.000010592 .000039156 -.000010549

N .000006740 -.000049240 .000004302

N -.000005250 .000004290 .000005820

H .000000512 .000000866 .000001586

H .000007530 -.000000209 .000002596

RMP2/6-31G(d,p)

C -.000001216 -.000000834 .000000705

C .000000017 .000002405 .000000315

C .000001308 -.000000637 -.000000282


178

C .000000140 -.000001608 -.000000020

H -.000000422 .000000457 -.000000037

H -.000000109 -.000000339 -.000000217

H .000000523 .000000005 .000000448

H -.000000130 -.000000419 -.000000165

C .000000833 -.000000028 .000000073

H -.000000175 .000000253 -.000000236

N -.000000644 .000000342 -.000000667

N .000000020 -.000000243 .000001114

N -.000000333 .000001157 -.000000525

H -.000000476 -.000000400 -.000000864

H .000000664 -.000000113 .000000357


RB3LYP/6-31G(d,p)

C -.000115935 .000043503 .000092751

C .000041974 -.000006554 .000027102

C -.000052727 .000008778 -.000019405

C .000010408 .000034357 -.000003307

H -.000005495 -.000001191 .000006913

H .000001600 .000003969 .000009131


179

H .000008223 .000000706 .000000626

H .000001741 -.000018395 -.000025051

C .000109860 -.000039757 -.000088742

H -.000010101 -.000009395 .000013274

N .000000091 -.000009885 -.000003770

N .000016074 -.000057557 .000017052

N -.000002307 .000033180 -.000019164

H .000009115 .000006054 .000001188

H -.000012521 .000012188 -.000008597

RHF/6-31G(d,p)

C -.000020438 .000025275 -.000011869

C -.000010480 -.000042605 .000003892

C .000018637 .000028225 .000003773

C -.000016696 -.000004129 .000001149

H .000004406 .000003418 .000002207

H .000003713 -.000003020 .000003132

H -.000000250 -.000006359 -.000002426

H .000007718 .000000031 -.000013502

C .000040601 -.000031066 .000018035

H -.000002836 .000000956 -.000011284

N -.000095225 -.000164064 -.000103872

N .000065211 .000210404 .000035258

N .000048685 -.000054646 .000059051

H .000000418 -.000004229 .000005735

H -.000043465 .000041810 .000010721


180

RMP2/6-31G(d,p)

C .000003949 .000009278 -.000018906

C -.000013832 -.000005142 -.000006159

C .000014893 .000003137 .000018088

C -.000016440 .000000916 .000000605

H -.000000524 .000001149 -.000000427

H -.000001417 .000000874 .000001676

H -.000001621 .000000009 .000000031

H .000006364 -.000000205 -.000010115

C .000012297 .000002412 .000006852

H .000000995 -.000000956 -.000004679

N -.000040562 -.000028027 -.000019434

N .000025313 -.000004330 .000024259

N .000018746 .000028045 -.000002175

H .000000192 -.000000048 .000001059

H -.000008353 -.000007113 .000009325

Reactant-2 (15)

RB3LYP/6-31G(d,p)

C .000003989 -.000000024 -.000002043

C .000000553 .000003672 -.000005123


181

C -.000002065 .000004929 -.000002931

C -.000001936 -.000000805 -.000001703

H .000002141 -.000000854 .000004916

H .000003202 .000000601 .000004457

H -.000003566 .000001451 -.000005584

H -.000003600 -.000002463 -.000002110

C -.000003006 .000000683 .000005272

H .000000540 -.000001812 .000003962

N .000002879 .000002354 .000000421

N -.000001085 -.000005761 .000003243

N -.000000405 .000001268 -.000000646

H .000004480 -.000001194 -.000007597

H -.000002123 -.000002045 .000005469

RHF/6-31G(d,p)

C -.000000079 .000005550 -.000000901

C -.000000464 .000001052 .000000045

C .000000233 .000000631 -.000000856

C -.000001159 .000000676 -.000000971

H .000004412 -.000000198 .000002645

H .000000228 .000000999 -.000002083

H .000000721 .000000157 -.000000115

H -.000000474 -.000001543 .000000552

C -.000001849 -.000005674 .000010980

H .000001968 .000000352 .000002301

N .000003282 .000008460 -.000000115

N -.000008149 -.000015955 -.000020082


182

N .000003337 .000007629 .000013351

H -.000001640 -.000000007 -.000000693

H -.000000367 -.000002128 -.000004059

RMP2.6-31G(d,p)

C .000005463 -.000010452 .000004784

C -.000001354 .000000813 -.000001247

C -.000002597 -.000004827 .000005008

C -.000001414 -.000000178 -.000001865

H -.000000870 -.000000851 -.000003351

H -.000000790 .000004613 -.000002971

H .000000552 .000004589 .000001061

H .000000757 -.000001979 -.000001045

C .000002079 .000010879 -.000000799

H .000003538 -.000003469 -.000000018

N -.000008667 .000004144 .000000572

N .000010591 -.000003335 -.000010341

N -.000004606 .000000018 .000007351

H .000000386 -.000002051 .000001898

H -.000003067 .000002085 .000000962

Product-2 (16)


183

RB3LYP/6-31G(d,p)

C .000001200 .000000615 -.000001090

C -.000001100 .000003225 -.000001637

C -.000003226 .000002643 -.000000145

C -.000002036 -.000000827 .000002845

H .000000453 .000001380 -.000001513

H -.000002043 .000006156 -.000002773

H -.000003915 -.000000666 .000004327

H -.000000333 -.000003426 .000003575

C .000003380 -.000002594 -.000001110

H .000004967 -.000004373 -.000001247

N .000001102 -.000000104 -.000001174

N .000000904 -.000000940 -.000000252

N .000000925 -.000002445 .000001318

H -.000004148 .000004875 -.000000001

H .000003868 -.000003521 -.000001122

RHF/6-31G(d,p)

C .000000827 .000000578 .000001037

C -.000000600 -.000001046 -.000000951

C -.000000451 -.000000846 .000000099

C .000002234 .000000043 -.000000232

H -.000000572 .000000382 -.000000157

H -.000000415 .000000787 -.000000067

H .000000155 .000001310 .000000919

H .000001186 -.000000780 -.000000984

C .000000179 .000000232 -.000000202


184

H -.000000342 -.000000377 .000000049

N -.000004373 -.000001150 -.000001086

N .000007218 .000003042 .000003659

N -.000006071 -.000002961 -.000001570

H .000000061 .000000678 -.000000407

H .000000964 .000000109 -.000000108

RMP2/6-31G(d,p)

C .000000582 .000001303 .000000496

C -.000002467 -.000000334 .000000915

C -.000000410 -.000000584 .000000548

C .000000670 .000000164 .000002750

H -.000000044 .000000096 -.000000006

H .000000064 .000000019 -.000000072

H -.000000503 .000001607 -.000000615

H .000000974 -.000000551 .000000884

C -.000000645 -.000000733 -.000000502

H .000000277 .000000203 -.000000069

N .000001894 .000000154 .000001190

N .000000258 -.000001315 .000002295

N -.000001554 .000001493 -.000005957

H .000000717 -.000001415 -.000001653

H .000000186 -.000000107 -.000000206


185


RB3YLP/631G(d,p)

C -.000003782 -.000011996 .000000893

C .000000536 .000020691 .000003738

C .000000517 -.000003348 -.000001138

C -.000002929 -.000000432 .000001837

H -.000000929 .000000945 .000001221

H .000000689 .000023082 .000002010

H -.000002341 .000002852 -.000000432

H -.000003970 -.000008009 .000002963

C -.000005313 -.000008379 -.000003651

H -.000007628 -.000007728 .000001817

N .000014892 -.000003747 -.000007050

N .000011965 .000006272 .000014484

N .000013098 .000003158 -.000010825

H .000001515 .000008690 .000000667

H -.000016320 -.000022051 -.000006534

RHF/6-31G(d,p)

C -.000002212 -.000005151 -.000000636

C .000000731 .000000307 .000002034


186

C .000005671 -.000001506 -.000015186

C -.000002128 -.000006650 .000005226

H .000001462 .000002764 -.000003267

H -.000000250 .000003447 .000006770

H -.000001383 .000004379 .000002855

H -.000002195 -.000000206 .000003838

C -.000003718 .000000071 -.000022840

H .000002009 .000002407 .000000086

N .000004977 -.000004565 .000032361

N -.000120134 -.000078578 -.000067055

N .000119798 .000084100 .000057460

H -.000001110 -.000000895 .000002740

H -.000001518 .000000076 -.000004386

RMP2/6-31G(d,p)

C -.000004286 .000029426 .000003589

C -.000022049 -.000013768 -.000002962

C .000015957 .000006575 .000015585

C -.000006549 .000010472 -.000009495

H -.000000597 .000001139 .000000894

H .000000337 -.000000553 -.000000623

H .000000301 -.000000558 .000000631

H -.000000044 .000002278 -.000000886

C -.000000450 -.000007081 -.000011509

H -.000000088 .000004706 .000001480

N .000021798 -.000011114 .000010899

N .000042573 .000019956 .000014684


187

N -.000052488 -.000034061 -.000018543

H .000000699 -.000002216 -.000002233

H .000004887 -.000005202 -.000001510

Transition state-4 (18)

RB3LYP/6-31G(d,p)

C .000008727 .000031088 -.000017568

C .000003595 .000004816 -.000001792

C -.000005457 -.000005023 -.000002184

N -.000001860 -.000002106 .000002370

N -.000008902 .000001461 -.000007128

N .000006229 -.000002273 -.000000270

H -.000002421 .000000020 .000001664

H -.000000255 -.000001664 .000000287

H -.000000205 .000001624 -.000001433

H .000000304 .000001536 -.000000433

C -.000000391 -.000027450 .000016263

H .000001011 .000000987 .000003328

C -.000000413 -.000001294 .000002064

H -.000001272 -.000000994 .000001290

H .000001311 -.000000728 .000003541


188

RHF/6-31G(d,p)

C -.000000879 -.000000345 .000000235

C .000001076 .000000292 -.000000466

C .000001233 -.000001851 -.000000512

N .000012185 .000003463 .000001658

N -.000018915 -.000007944 -.000003221

N .000005508 .000005992 .000001974

H .000000040 .000000055 .000000331

H .000000011 -.000000039 -.000000370

H -.000000183 .000000293 .000000435

H -.000000303 .000000190 .000000110

C -.000000192 -.000000257 .000000220

H .000000047 -.000000281 -.000000091

C .000000378 .000000459 -.000000314

H .000000014 .000000000 .000000030

H -.000000018 -.000000029 -.000000019

RMP2/6-31G(d,p)

C .000005164 -.000003180 -.000004816

C -.000000048 -.000003547 -.000001206

C .000001347 -.000002096 .000003234

N .000020559 .000000425 -.000000889

N -.000010540 .000008491 .000005719

N -.000014153 -.000003772 -.000003972

H -.000001099 -.000000553 .000001352

H -.000000064 .000000630 -.000001740

H .000002045 .000000854 .000000350


189

H .000000231 -.000000478 -.000000233

C -.000003697 .000002820 .000002140

H .000000317 .000000736 .000000372

C -.000000096 -.000000225 -.000000275

H -.000000038 .000000191 -.000000019

H .000000073 -.000000297 -.000000017

Product-4 (19)

RB3LYP/6-31G(d,p)

C .000005311 -.000001130 .000002244

C -.000000346 .000005267 .000001524

C .000000647 .000000812 -.000001184

N -.000002518 -.000001904 .000002349

N .000001914 -.000001310 -.000001596

N .000000302 -.000001387 .000006845

H -.000000639 .000002063 -.000001009

H .000002232 .000001140 -.000000691

H .000000710 .000000598 -.000001193

H -.000002335 -.000000885 -.000000755

C .000000827 -.000008068 .000004960

H -.000003989 .000002221 -.000000959

C .000000476 .000005058 .000001138

H .000000412 .000001498 -.000007116

H -.000003004 -.000003972 -.000004557


190

RHF/6-31G(d,p)

C .000004845 .000003526 -.000000850

C .000000081 -.000001456 .000000578

C -.000000393 .000000785 -.000000531

N -.000002920 -.000004322 .000000954

N .000001101 .000002720 .000002014

N -.000002718 -.000001623 -.000001627

H -.000000144 .000000024 -.000001034

H -.000000110 -.000000099 -.000000839

H -.000000089 .000000758 .000000320

H .000000264 .000000055 .000000892

C -.000001576 -.000000307 .000000436

H .000000127 .000000201 .000000850

C .000000820 -.000000266 -.000000588

H -.000000091 .000000135 -.000000838

H .000000805 -.000000133 .000000263

RMP2/6-31G(d,p)

C .000000394 .000002053 -.000000266

C .000002236 -.000001818 -.000002524

C .000000026 -.000001880 .000001002

N -.000003638 .000004276 .000003550

N -.000004226 -.000005727 -.000006029

N .000007797 .000001537 .000003841

H .000000151 .000001250 -.000000582

H .000000016 -.000000138 -.000000127

H -.000000203 .000000620 .000000278


191

H -.000000232 -.000000496 .000000812

C -.000001089 -.000000192 -.000001661

H .000000257 .000000143 .000000759

C -.000002074 .000000146 .000001080

H -.000000078 -.000000240 -.000000437

H .000000663 .000000466 .000000304

Interconversion of cis- and trans-1-azido-2-butene, via a sequential [3, 3] sigmatropic

rearrangements at RB3LYP/6-31G(d,p)

Transition state of trans#-1-azido-2-butene (6)

C -.000011243 .000001152 .000010903

C .000004330 -.000009025 -.000002149

C -.000000118 -.000003188 -.000001174

N .000005040 -.000027169 .000001252

N .000002993 .000018131 -.000012534

N .000000186 .000005826 -.000001339

H -.000006280 .000000595 -.000008737

H -.000004890 .000000965 .000003052

H -.000000531 -.000000669 .000003138

H .000003420 -.000002858 .000002552

C -.000009057 .000017667 -.000026576

H .000005818 .000007001 -.000006267


192

H .000002539 -.000007087 .000004733

H .000007792 -.000001341 .000033147

Transition state of cis#-1-azido-2-butene (7)

C .000021499 .000010173 .000022868

C .000004243 -.000005368 -.000008018

C .000003249 -.000006449 .000001628

N -.000003210 -.000058332 .000002315

N .000005156 .000068051 .000002117

N -.000010796 .000013095 -.000002284

H -.000005470 -.000000062 -.000004640

H -.000010004 -.000000175 .000000211

H -.000004951 -.000000444 -.000001686

C -.000012046 .000005465 -.000012124

H .000001884 -.000008175 .000008388

H .000002837 -.000014163 -.000005802

H .000002939 -.000000123 .000013082

H .000004669 -.000003493 -.000016054


193

cis-1-azido-2-butene (4)

C -.000009371 -.000001332 -.000003605

C .000010080 .000000310 .000000993

C -.000010101 -.000007010 .000014308

H .000004410 -.000001224 .000000124

N .000003304 .000003506 -.000002888

N .000001446 .000002995 -.000003086

N .000000430 .000003883 -.000005261

H .000000980 .000006492 -.000001756

H .000001609 -.000007898 .000007401

H .000007191 .000000229 .000001456

C -.000018593 -.000008774 .000005390

H .000002248 .000000576 .000000274

H .000004997 -.000004107 -.000004986

H .000001371 .000012355 -.000008361

trans-1-azido-2-butene (2)

C .000000468 -.000002243 -.000001740

C .000007628 -.000000093 -.000003664

C -.000000560 -.000012497 .000014870


194

H -.000002369 -.000000493 -.000003687

N -.000002016 -.000002319 -.000002891

N -.000000207 -.000001697 .000000219

N .000000942 -.000002894 .000001096

H -.000001915 .000001526 -.000002338

H -.000008864 .000004210 .000002220

H -.000004889 -.000006773 -.000002376

C .000009464 .000011693 -.000004564

H -.000005249 -.000007983 -.000009249

H .000000212 .000021259 .000010964

H .000007356 -.000001697 .000001140

3-azido-1-butene (3)

C -.000001035 .000000833 -.000000380

C .000001296 .000001470 -.000000225

C .000001590 .000001086 -.000001965

N .000001081 -.000001774 -.000000337

N .000000298 -.000002666 .000004990

N .000002607 -.000003627 -.000000915

H .000000162 -.000001453 -.000000059

H .000003046 .000001288 -.000002405

H .000002545 .000002629 -.000002958

H -.000001045 .000002092 -.000000658


195

C -.000002426 .000001125 .000001644

H -.000000960 -.000002158 .000001557

H -.000003472 .000000789 -.000000324

H -.000003687 .000000365 .000002035


196

APPENDIX-B

1H-NMR,

13C-NMR, HMQC AND COSY SPECTRA


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Copyright 2011, Deepali Butani

Documents

Transcript of Copyright 2011, Deepali Butani