ELECTROPHILIC SUBSTITUTION IN AROMATIC SYSTEMS A thesis submitted by BRIAN JONES

328 Pages·2017·7.77 MB·English

ELECTROPHILIC SUBSTITUTION
IN
AROMATIC SYSTEMS
A thesis submitted
by
BRIAN JONES
C-
to the University of Wales
in candidature for the degree of
Philosophiae Doctor
School of Physical and Molecular Science,
University College of North Wales,
Bangor. January, 1979.
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For my parents.
ABSTRACT
The nitrodecarboxylation of 2-acetamidothiophene-3-carboxylic acid was
investigated in an attempt to improve the yield of 2-acetamido-3,S-
dinitrothiophene obtained as product. The latter compound is valuable
as an intermediate in the dyestuffs industry. It was found that both
2-acetamido-5-nitrothiophene-3-carboxylic acid and 2-acetamido-3,5-
dinitrothiophene are susceptible to hydrolysis to unstable amines in the
nitrating medium, a mixture of sulphuric and nitric acid.
The rates of nitrodecarboxylation of a variety of substituted
thiophenes were determined as a function of sulphuric acid concentration •.
The characteristics of the reaction were found to be similar to those of
conventional nitrodeprotonation. although the latter reaction is
C0 H
considerably faster, (the ipso factor, i 2 for nitrodecarboxylation
f
4
was found to be S.6x10- ). Ring systems in which the carbon atom
containing the carboxyl group is activated towards electrophi1ic attack
are particularly susceptible to nitrodecarboxy1ation. A Hammett reaction
constant. p+, of -4.6 was obtained for the nitrodecarboxy1ation reaction,
the reaction constant for the corresponding nitrodeprotonation reaction
being -3.4. A concerted mechanism, similar to that for conventional
nitration, is favoured for the nitrodecarboxy1ation reaction.
The rates of hydrolysis of a variety of amido-thiophenes were also
determined as p function of sulphuric acid concentration. In concentrated
acid most amides were hydrolysed by the unimolecu1ar A1 mechanism whereas
in more dilute acid the bimolecular A2 mechanism of hydrolysis predominated.
The amino-thiophenes produced were particularly unstable in presence of
nitric acid. This hydrolysis to an unstable amine partially accounts for
the unsatisfactory yield of 2-acetamido-3,S-dinitrothiophene-3-carboxy1ic
acid in sulphuric-nitric acid. Indeed, the stability of the corresponding
formamido derivatives to hydrolysis is reflected in the improved yield
of 2-formamido-3.5-dinitrothiophene obtained by a similar nitration
process (70.3% compared with 46.2% for the acetamido derivative).
Unsuccessful attempts were made to isolate oxidation products of
unstable thiophene derivatives and the rates of oxidation were determined
in sulphuric-nitric acid mixtures.
ACKNOWLEDGEMENTS
I wish to express my sincere thanks to Prof. C.J.M. Stirling and
Or. o.R. Marshall, of U.C.N.W., Bangor. and Or. B.R. Fishwick of I.C.I.,
Manchester for their help, guidance and encouragement throughout the course
of this work.
I should also like to thank the technical staff at U.C.N.W. and I.C.I.
for their ready assistance and co-operation, especially Mr. E. Lewis
for the provision of the micro-analysis service. I am also grateful to
Mrs. Pat Pritchard and my wife for their assistance in producing the
manuscript.
Finally I wish to express my gratitude to the Science Research
Council and I.C.I. Organics Division for providing me with a research
grant.
CONTENTS
. . . . . . . . . . . . . . . . . . . . .
PART 1 INTRODUCTION
1
. . . . . . . . . . .
Chapter 1 - The Industrial Process
2
. . . . . . .
2-Amino-3.S-Dinitrothiophene
5
. . .
Chapter 2 - Thiophene Chemistry
9
Structure 10
. . . . . . . . .
Chemical Properties 11
Thiophene Derivatives of Industrial Significance 13
Nucleophilic Substitution in Thiophene Derivatives 16
. . . . .
Substitution with Elimination of Substituents • 17
. . . . . . . . . . . . . . . . . . . . . .
Surrrnary 17
. . . . . . .
Chapter 3 - Reactions in Sulphuric Acid 20
. . .
Sulphuric Acid/Water Mixtures • 21
Acidity Functions •••••••••••• 23
Nitration in Sulphuric Acid • • • • • • •• 26
Decarboxylations in Sulphuric Acid • • • • • • 37
Protonation of Amides • • • • • • • • • • • • • 40
· . . . . . . . .
PART 2 ELECTROPHILIC OISPU\CEMENT REACTIor~S 43
Chapter 4 - Introduction to Electrophilic Substitution · · · 44
. . . . . . . . . . .
Nitration · · · · · · · · · · 45
.
Anomalous Substitution Reactions · · · · · · 48
Ipso Factors/Ipso Substitutions · · · · · · 49
Heterocyclic Compounds · · · · · · 54
Leaving Group Ability · · · 56
Other Consequences of Ipso Attack · · · · · · · 63
. . . . . . . . . .
Summary · · · · · · · · · · · · 65
Chapter 5 - Nitrodecarboxylation of Thiophene Derivatives •• 66
· .
2-Acetamido-5-Nitrothiophene-3-Carboxylic Acid 67
. . . .
2-Acetamido-5-Nitrothiophene 73
. . . .
Ipso Factors • • • • • • • • • 76
2-Acylamino-5-Nitrothiophene-3-Carboxylic Acids. 76
Other Substituted Thiophenes ••••••• 80
2-Substituted-3-Nitrothiophene-5-Carboxylic Acids 86
. . . . . . . . . . . . . . . . . .
Hammett Plots 98
Comparison of Nitrodecarboxylation and Nitrodeprotonation 102
Summary and Conclusions .•.•. ' •••••.••. .• 105
· . . . . . . . . . . .
PART 3 HYDROLYSIS OF THIOPHENE-AMIDES 110
.
Chapter 6 - General Amide Hydrolysis · · · · · · · · · 111
. . . .
Basic Hydrolysis · · · · · · · · · · 112
. . .
Acid Hydrolysis · · · • · 115
. . . .
i) The A2 Mechanism · · · · · · 116
ii) The A1 Mechanism · · · · · 125
. . . .
Chapter 7 - Hydrolysis of Thiophene Amides 133
· . . . . . . .
13C Spectral Analysis 134
. . . .
Hydrolysis in Concentrated Sulphuric Acid • 140
. . . . . .
i) Unimolecular (A1) Mechanism. 143
. .
. . . . .
iiI Bimolecular [A21 Mechanism 152
Basic Hydrolysis of Amidothiophenes 155
. . . . . . . . . . . . . . . . . .
Summary 157
Page
PART 4 DEGRADATION OF THIOPHENE DERIVATIVES ••••••••• 160
Chapter 8 - Introduction to Reactions involving destruction of
. .
the Thiophene Nucleus • 161
. . . . . . . .
Polymerisation • • • 162
. . . . . . . . . . . . . .
Reduction • 162
. . . . . . . . .
Pyrolysis • • • 163
. . .
Oxidative Degradation • • 164
Chapter 9 - Degradation (Oxidation) of Thiophene Derivatives 166
Degradation via Hydrolysis • • 168
. . . .
2-Acylamino-3.5-Dinitrothiophenes • 170
. .
Substituent Effects • • • • • • • • 172
. . .
Isolation of Oxidation Products 174
. . . . . . . . . . . . . . . . . . . .
Sunmary 176