Mechanistic Studies Of The Reactions Of Some
Transcript Of Mechanistic Studies Of The Reactions Of Some
MECHANISTIC STUDIES OF THE REACTIONS OF SOME ALLYLIC HALIDES A thesis presented by Mohammac Rahimizadeh for the degree of Doctor of Philosophy of the University of London
September 1977
AB T.-/ACT
A review of nucleophilic substiWtion is set forth, in which the diffPrent techniques available for the elucidation of reaction mechanism are described. Allylic solvolytic reactions are briefly summarised.
An account is given of the synthesis of several new (reactive) allyli.c chlorides. A chlorination method particularly useful for the preparation of very reactive or volatile allelic chlorides is described.
The solvolytic reactions (solvolyses) of 5-chloropent-3-en-l-yne and 3-chloro-pent-4-en-l-yne are studied and possible mechanisms are propounded. The solvolytic mechanism for the former compound is of a bimolecular type and it is suggested that the rate determining step is fortnation of a nucleophilically solvated ion-pair intermediate. However, for the latter compound the mechanism has a unimolecular character, and product distributions are explained by the involvement of two discrete ion-pair intermediates. It is suggested that the rearrangement ana solvolysis reactions have the same ion-pair intermediate for the 3-(qiloro compound.
The isomerisation of 3-chloro-pent-4-en-l-yne has been studied in sulpholane at different salt concentrations. The reaction is shown to follow unimolecular kinetics in the absence of lithium chloride (chloride ion). However, lithium chloride accelerates the reaction so that the composite rate of rearrangement becomes dominated by a bimolecular nrocess.
To my Parents
ACKNOWLEDGEMENTS
I am most grateful to my supervisor Dr E S Weight for his patience, guidance and encouragement during the course of this research. I am also indebted to Professor Sir Derek Barton for the opporunity of working in the Chemistry Department.
The technical co-operation of Mr R Carter and his staff is greatly appreciated. My special thanks go to Mr J Bilton for his friendly assistance, Mrs J Lee in obtaining mass spectra and Mr E Pepper for his cooperation with instrument service. I would like to express my sincere thanks to Mrs B Day and Mrs I Hamblin in the Organic Store for their friendship.
My deepest thanks go to my friends and colleagues Mr J Bilton, Ms M A Baguena and Dr N Kyriakidis whose friendship will always be remembered. I would also like to mention my late friend Mr H Rahman. I also wish to thank Miss B Johnston for typing the manuscript. Finally, I am greatly indebted to the Ministry of Science and Higher Education of Iran for providing financial support.
CONTENTS
INTRCDUCTION CHAPTER 1 1. Nucleophilic Substitution Reactions
1.1 Normal Bimolecular Nucleophilic substitution
1.2 Abnormal Bimolecular Nucleophilic substitution
1.3 Unimolecular Nucleophilic Substitution 1.4 Nucleophilic Substitution of Borderline
Type Substrates 1.5 Ion-pair Intermediate in the Reactions
of Allylic Substrates 1.6 Allylic Solvolytic Reactions
CHAPTER 2 2. Result and Discussion of Synthetic Work
Page 1
6 6 9 13 15 19 29
40
CHAPTER 3
3. Result and Discussion of Solvolytic Reactions of
3-chloro-pent-4--en-i-yne and 5-chloro-pent-3-en-
1-yne
53
3.1 The Vinyl-acetylene System
54
3.2 Solvolysis of 3-chloro-pent--4-en-1-yne
58
3.2.1. The Effect of Solvent Ionizing
Power
58
3.2.2 The Salt Effect
62
3.2.3 The Common Ion Effect
CV
3.2.4 Result and Discussion
72
3.3 Solvolysis of 5-chloro-pent-3-en-l-yne
78
3.3.1 Result
78
3.3.2 Discussion and Conclusion
85
CHAPTER 4
4. Rearrangement of 3-chloro-pent-4-en-l-yne
92
4.1 Introduction and Result
93
4.2 Discussion and Conclusion
98
CHAPTER 5
5. Experimental
103
5.1 Preparations of Materials
104
5.2 Solvents
5.3 Salts
122
5.4 Kinetics
124
5.5 Examples of Kinetic Runs
129
REFERENCES
134
INTRODUCTION
2.
INTRODUCTION
The chemistry of allylic compounds, which have
the part-structure 1, has played an important part in the
development of theoretical organic chemistry. These
substances owe their importance to the high reactivity that
they display in nucleophilic substitution and to the fact
that they readily undergo rearrangement reactions. For
this reason allylic intermediates are widely used in organic
synthesis.
C = C - C X
(1)
In addition, allylic systems are found in many
natural products, such as alkaloids, steroids and terpenes.
Allylic systems are particularly common among the terpenes,
and allylic substitution reactions are widely used in the
synthesis of essential oils, vitamin A and its analogs, and
other un$aturated compounds.
Rearrangements in allylic compounds have been long 1/ known. A typical isomeric rearrangement is the conversion
2/ of 1-phenylallyi ester into its 3-isomer:—
PhCH(OCOR)CH = CH2
PhCH = CHCH2 OCOR (1) 3/
It was first clearly recognised by Burton and Ingold chat such reactions may involve migration of a nucleophilic 02 anionic fragment from one end of the alllic system to the other. They are frequently found to accompany nucleophilic displacements in the allylic system. Rearrangement
3.
reactions of this type belong to the class of reactions
known as anionotropic rearrangement. The term anionotropy,
introduced by Ingold refers to molecular rearrangement
9
0
where the migrating groups are anions as OH, OR Cl etc.
4/
•
Anionotopy has been redefined by Braude as the migration
of a group or atom in which that group or atom retains the
electrons by which it was originally bound to the molecule.
The equilibrium in an anionotopic system can be considered
quite independently of the mechanism of the rearrangement
but depends on the free energy difference (AG) between the
isomeric structures expressed in equation (2).
A G == - RT to K
(2)
For qualitative and semiquantitative discussion it is usually
sufficiently accurate to identify (AG) with the change in heat content and to discuss the effect of substituents attached to the carbon atoms C1, C 2 and C3 in terms of what is known of the stabilization energies resulting from the presence of substituents adjacent to the C1-C2 double bond in the first isomer and the C2-C3 double bond in the second isomer. For example, the equilibrium mixture of cinnamJ ana 1-phenylallyl chlorides contains no detectable quantities of the latter (equation 1) and the composition of the equilibrium mixture between crotyl and l-methyl-allyl ehorides
5/ or bromides :
(75-85)% CH3-CH==CH-Ci 2X
CH3-CHX-CH==CH2 (15-25)%
(3)
depends on the halides and the temperature. A study of the
aniontropic rearrangement occurring during a displacement
reaction can yield valuable information concerning the
4.
mechanism of the latter reaction. Allylic halides display the properties of ease of nucleophilic substitution and anionotropic mobility to a high degree, and in the following sections mechanistic aspects of these reactions . will be discussed with particular reference to solvolytic reactions. Isomerization reactions of allylic alcohols, esters and ethers have been reviewed by Braude. De Wolfe
(4, 6, 7) and Young.
September 1977
AB T.-/ACT
A review of nucleophilic substiWtion is set forth, in which the diffPrent techniques available for the elucidation of reaction mechanism are described. Allylic solvolytic reactions are briefly summarised.
An account is given of the synthesis of several new (reactive) allyli.c chlorides. A chlorination method particularly useful for the preparation of very reactive or volatile allelic chlorides is described.
The solvolytic reactions (solvolyses) of 5-chloropent-3-en-l-yne and 3-chloro-pent-4-en-l-yne are studied and possible mechanisms are propounded. The solvolytic mechanism for the former compound is of a bimolecular type and it is suggested that the rate determining step is fortnation of a nucleophilically solvated ion-pair intermediate. However, for the latter compound the mechanism has a unimolecular character, and product distributions are explained by the involvement of two discrete ion-pair intermediates. It is suggested that the rearrangement ana solvolysis reactions have the same ion-pair intermediate for the 3-(qiloro compound.
The isomerisation of 3-chloro-pent-4-en-l-yne has been studied in sulpholane at different salt concentrations. The reaction is shown to follow unimolecular kinetics in the absence of lithium chloride (chloride ion). However, lithium chloride accelerates the reaction so that the composite rate of rearrangement becomes dominated by a bimolecular nrocess.
To my Parents
ACKNOWLEDGEMENTS
I am most grateful to my supervisor Dr E S Weight for his patience, guidance and encouragement during the course of this research. I am also indebted to Professor Sir Derek Barton for the opporunity of working in the Chemistry Department.
The technical co-operation of Mr R Carter and his staff is greatly appreciated. My special thanks go to Mr J Bilton for his friendly assistance, Mrs J Lee in obtaining mass spectra and Mr E Pepper for his cooperation with instrument service. I would like to express my sincere thanks to Mrs B Day and Mrs I Hamblin in the Organic Store for their friendship.
My deepest thanks go to my friends and colleagues Mr J Bilton, Ms M A Baguena and Dr N Kyriakidis whose friendship will always be remembered. I would also like to mention my late friend Mr H Rahman. I also wish to thank Miss B Johnston for typing the manuscript. Finally, I am greatly indebted to the Ministry of Science and Higher Education of Iran for providing financial support.
CONTENTS
INTRCDUCTION CHAPTER 1 1. Nucleophilic Substitution Reactions
1.1 Normal Bimolecular Nucleophilic substitution
1.2 Abnormal Bimolecular Nucleophilic substitution
1.3 Unimolecular Nucleophilic Substitution 1.4 Nucleophilic Substitution of Borderline
Type Substrates 1.5 Ion-pair Intermediate in the Reactions
of Allylic Substrates 1.6 Allylic Solvolytic Reactions
CHAPTER 2 2. Result and Discussion of Synthetic Work
Page 1
6 6 9 13 15 19 29
40
CHAPTER 3
3. Result and Discussion of Solvolytic Reactions of
3-chloro-pent-4--en-i-yne and 5-chloro-pent-3-en-
1-yne
53
3.1 The Vinyl-acetylene System
54
3.2 Solvolysis of 3-chloro-pent--4-en-1-yne
58
3.2.1. The Effect of Solvent Ionizing
Power
58
3.2.2 The Salt Effect
62
3.2.3 The Common Ion Effect
CV
3.2.4 Result and Discussion
72
3.3 Solvolysis of 5-chloro-pent-3-en-l-yne
78
3.3.1 Result
78
3.3.2 Discussion and Conclusion
85
CHAPTER 4
4. Rearrangement of 3-chloro-pent-4-en-l-yne
92
4.1 Introduction and Result
93
4.2 Discussion and Conclusion
98
CHAPTER 5
5. Experimental
103
5.1 Preparations of Materials
104
5.2 Solvents
5.3 Salts
122
5.4 Kinetics
124
5.5 Examples of Kinetic Runs
129
REFERENCES
134
INTRODUCTION
2.
INTRODUCTION
The chemistry of allylic compounds, which have
the part-structure 1, has played an important part in the
development of theoretical organic chemistry. These
substances owe their importance to the high reactivity that
they display in nucleophilic substitution and to the fact
that they readily undergo rearrangement reactions. For
this reason allylic intermediates are widely used in organic
synthesis.
C = C - C X
(1)
In addition, allylic systems are found in many
natural products, such as alkaloids, steroids and terpenes.
Allylic systems are particularly common among the terpenes,
and allylic substitution reactions are widely used in the
synthesis of essential oils, vitamin A and its analogs, and
other un$aturated compounds.
Rearrangements in allylic compounds have been long 1/ known. A typical isomeric rearrangement is the conversion
2/ of 1-phenylallyi ester into its 3-isomer:—
PhCH(OCOR)CH = CH2
PhCH = CHCH2 OCOR (1) 3/
It was first clearly recognised by Burton and Ingold chat such reactions may involve migration of a nucleophilic 02 anionic fragment from one end of the alllic system to the other. They are frequently found to accompany nucleophilic displacements in the allylic system. Rearrangement
3.
reactions of this type belong to the class of reactions
known as anionotropic rearrangement. The term anionotropy,
introduced by Ingold refers to molecular rearrangement
9
0
where the migrating groups are anions as OH, OR Cl etc.
4/
•
Anionotopy has been redefined by Braude as the migration
of a group or atom in which that group or atom retains the
electrons by which it was originally bound to the molecule.
The equilibrium in an anionotopic system can be considered
quite independently of the mechanism of the rearrangement
but depends on the free energy difference (AG) between the
isomeric structures expressed in equation (2).
A G == - RT to K
(2)
For qualitative and semiquantitative discussion it is usually
sufficiently accurate to identify (AG) with the change in heat content and to discuss the effect of substituents attached to the carbon atoms C1, C 2 and C3 in terms of what is known of the stabilization energies resulting from the presence of substituents adjacent to the C1-C2 double bond in the first isomer and the C2-C3 double bond in the second isomer. For example, the equilibrium mixture of cinnamJ ana 1-phenylallyl chlorides contains no detectable quantities of the latter (equation 1) and the composition of the equilibrium mixture between crotyl and l-methyl-allyl ehorides
5/ or bromides :
(75-85)% CH3-CH==CH-Ci 2X
CH3-CHX-CH==CH2 (15-25)%
(3)
depends on the halides and the temperature. A study of the
aniontropic rearrangement occurring during a displacement
reaction can yield valuable information concerning the
4.
mechanism of the latter reaction. Allylic halides display the properties of ease of nucleophilic substitution and anionotropic mobility to a high degree, and in the following sections mechanistic aspects of these reactions . will be discussed with particular reference to solvolytic reactions. Isomerization reactions of allylic alcohols, esters and ethers have been reviewed by Braude. De Wolfe
(4, 6, 7) and Young.