Mechanism of nonactivated aromatic nucleophilic substitution

148 Pages·2009·3.5 MB·English

In presenting the dissertation as a partial fulfillment of
the requirements for an advanced degree from the Georgia
Institute of Technology, I agree that the Library of the
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7/25/68
MECHANISM OF NONACTIVATED AROMATIC NUCLEOPHILIC SUBSTITUTION
A THESIS
Presented to
The Faculty of the Graduate Division
by
Daniel Farmer Pinholster, Jr.
In Partial Fulfillment
of the Requirements f or the Degree
Doctor of Philosophy
in the School of .Chemistry
Georgia Institute of Technology
July, 1970
MECHANISM OF NONACTIVATED AROMATIC NUCLEOPHILIC SUBSTITUTION
Approved:
I.
,• • —..--^ ~ ,-
V
• Date approved by Chairman; ••. 9/9/7
11
ACKNOWLEDGMENTS
I gratefully thank Dr. C. L. Liotta for proposing the work
herein. His inspiration and enthusiasm provided the leadership which
led to the fulfillment of this research" For his many discussions
and helpful comments I will ever be thankful.
I thank Dr. E. Grovenstein, Jr. for reading and criticizing
this manuscript. I also thank him for his objective comments during
group discussions which provided new insight and directives for further
research.
I thank Dr. J. A. Stanfield for thoroughly reading and criti­
cizing this manuscript.
I am grateful to Mrs. Joyce Williams for the typing of this
manuscript.
i ii
TABLE OF CONTENTS
Page
ACKNOWLEDGMENTS ii
LIST OF TABLES . . . . . . . . . . . . . . .. vi
LIST OF FIGURES viii.
GLOSSARY OF ABBREVIATIONS . . . . . . . . . . . . .. ix
SUMMARY . . . . . . . . . . . . . . . . .. x
Chapter
I. HISTORICAL BACKGROUND ." . . . .. 1
Introduction
Nonrearranging 'Reactions
Nucleophiles
Amides and Amines
Alkoxides
Sodium Hydroxide and Sodium Cyanide Fusions
Sodium Hydroxide Hydrolysis Reactions
Halides
Diphenyl Phosphide
Acetates and Carbonates
Thiophenoxide
Carbanions
Leaving Groups
Nitro
Benzenesulfonate
Ammonia
Phenoxide
Thiophenoxide
Phenyl Sulfonyl and Methyl Sulfonyl
Sulfonate
Phenyl Iodonium Group
Halogen Order
Substituent Effects
Deactivating Substituents
Halogen Substituents
Intermediate Activating Substituents
Side Reactions
Linear Free Energy Relationships
The ortho:para Ratio
iv
TABLE OF CONTENTS (Continued)
Page
Solvent Effects
Mechanism
Rearranging Reactions
Sommelet-Hauser Rearrangement
Competitive (Benzyne vs Addition-Elimination)
Truce-Smiles Rearrangement
Miscellaneous
Azulene
Nucleophilic Aromatic Alkylation
Keto-enol Equilibrium
Anilenium Ion
II. EXPERIMENTAL . . . . . . . . . . . . .. kQ
Chemicals
Instrumentation
pH Meter and Titration Apparatus
Infrared Instrument
Ultraviolet Spectrophotometer
Melting Point Apparatus
Nuclear Magnetic Resonance Spectrophotometer
Constant Temperature Baths
Gas-Liquid Chromatography Instruments
Index of Refraction
Weighing Balances
Mass Spectrometer
Preparation of Solutions
'Syntheses and Product Identification
Reaction of 1,5-Dibromopentane with Substituted Anilines
N-(m- or p_-R-Phenyl)-piperidines from Aromatic Nucleophilic
Displacements
Further Studies of the Products from Nucleophilic
Displacement by Piperidine
Deuterated Compounds
Kinetic Procedures and Related Studies
Treatment of Kinetic Data
Reactions with Deuterated Compounds
III. DISCUSSION AND RESULTS . 90
Rate Data
Hammett Plot
Substituent Effects
Halogen Order and Activation Data
Element Effect
Base Catalysis
Deuterium Exchange
V
TABLE OF CONTENTS (Concluded)
Page
IV. CONCLUSIONS . . . . . . . . . . . . .. 119
V. RECOMMENDATIONS . . . . . . . . . . . . . .. 120
APPENDICES . 121
BIBLIOGRAPHY . . . . . . . . . .. . • 123
VITA 133
vi
LIST OF TABLES
Table Page
lo Classification of Substituents 2
2. Reaction of Halobenzenes and Halonaphthalenes with
Piperidines at l65°C . , k
3° Activation Data f or Bromonaphthalenes with Piperidine . h
kc Effect of t he Substrate on Reactivity with Piperidine
at 200°C . . . . . . . . . . . . . . . .. 6
5« Reactivity Data f or t he Reactions of Piperidine with
Halofurans at 200° C 6
6. Reaction of Substituted Chlorobenzenes with Aqueous
Ammonia at 270° C . . 8
7« Reactions of Amides with Substituted Benzenes and
Naphthalenes by Direct Displacement . . . . . .. 9
8. Reactions of Alkoxides with Haloaromatics . . . .. 11
9» Hydrolysis of p_-Substituted. Halotoluenes at 250° C . .. Ik
10. Relative Rates of Reaction of Halobenzenes with
Piperidine and Sodium Methoxide . . . . . . . .. 20
11. Rate Constants f or Substituted Fluoro- or Chlorobenzenes
with Sodium E t h o x i d e at 150°C . . . . . . . .. 22
12. Activating A b i l i ty of Substituents . . . . . . . .. 23
13- • Kinetic Parameters of t he Reaction of Substituted
Chlorobenzenes with Sodium Methoxide at 120°C . . .. 2h
ih. Kinetics of t he Reaction of Chlorobenzenes with
Sodium Methoxide at 210°C . . . . . . . . .. 2k
15. Halogen Substituent Effects at 200°C with
Sodium Methoxide . . . . . . . . . . . .. 26
16. Sigma Values 30
17• Hammett Plots 31
LIST OF TABLES (Continued)
Table
l8<. The ortho :para Effect of Carboxylate . . . . . ..
19 • The ortho: para Ratio of SOCgHg and SOgCgHg in Aqueous
Dimethyl Sulfoxide at 158°C . . . .
20. The ortho;para Ratio of COCHa and C0CHs
6
21. The ortho;para Ratio of the Trifluoromethyl Substituent .
22. The ortho:para Ratio of Chlorine and Bromine . . . .
23• Methylation of Aromatic Compounds
2k° Data on Substituted Anilines . . . . . . . ..
25° Data on Distilled Halobenzenes .
26. Compounds Not Purified . . . . . . . . . ..
27- Preparation of N- (X-Phenyl)-piperidines
28. UV Data on N-(X-Phenyl)-piperidines .
29« N-(m-or p_-Phenyl)-piperidines Isolated From the Reactions
of Piperidine with the Corresponding m- dr. p-Substituted
Fluorobenzenes in Triethylene Glycol at 19^--5°C
30. Experimental Per Cent Displacement ;iri Mixeid Dihaloben-
zenes . . . . . . . . . . . . . . . ..
31. Rate Data Sheet ' . .,
;
32. Second Order Data f or Reactions Carried out in
Triethylene Glycol . . . . . ..
33° Hammett Plot Data.for Substituted Fluorobenzenes
3k* Relative Rates of Substituted Halobenzenes in
Piperidine . . . . .. .
35* Calculated Per Cent Displacement in Mixed
Dihalobenzenes . . . .
36. Activation Data and Relative Rates of Halobenzenes
with Piperidine
37•. Amine Catalysis Data
V l . ll
LIST OF FIGURES
Figure Page
lo Plot of the Per Cent Hydrogen Incorporation into
N-(Phenyl-U-d)-piperidine vs. Time in the Reaction
of Piperidine with Fluorobenzene-U-d in TEG at 225°C . . Qk
2= Change in the Rate Determining Step 9^
3» Change in the Mechanism . 9k
k° Change in Mechanism in Aromatic Nucleophilic
Substitution . . . . . . . . . . . . . .. 95
5» Slight Change of Mechanism . . . . . . . . . .. 95
6. Hammett Plot for the Reaction of m-. and p-Substituted
Fluorobenzenes with Piperidine in Triethylene Glycol
at 19l|.5°C . . . . . . . . . . . . . .. . 96
7. Graphical Representation of the Reactivity in
Mixed Dihalobenzenes . . . . . . . . . . . . .. 105
8. Orbital Picture for the Thermal Disrotatory Cyclization of
Cyclohexadienyl Anion to Cyclopentenyl -Anion . . ' . . . 117