Advanced Organic Chemistry: Part A: Structure and Mechanisms

600 Pages·1995·15.441 MB·English

by  Francis A. Carey, Richard J. Sundberg (auth.)

Advanced Organic
Chemistry
Part A: Structure and Mechanisms
ADVANCED ORGANIC CHEMISTRY
PART A: Structure and Mechanisms
PART B: Reactions and Synthesis
Advanced Organic
Chemistry
Part A: Structure and Mechanisms
Francis A. Carey
and Richard 1. Sundberg
University of Virginia, Charlottesville, Virginia
PLENUM PRESS • NEW YORK AND LONDON
Library of Congress Cataloging in Publication Data
Carey, Francis A 1937-
Advanced organic chemistry.
Includes bibliographical references and indexes.
CONTENTS: pt. A. Structure and mechanisms.-pt. B. Reactions and synthesis.
1. Chemistry, Organic. I. Sundberg, Richard J., 1938- joint author. II. Title.
[DNLM: 1. Chemistry, Organic. QD258 C273a)
QD251.2.C36 547 76-26090
ISBN-13: 978-1-4615-8884-9 e-ISBN-13: 978-1-4615-8882-5
001: 10.1007/978-1-4615-8882-5
Softcover reprint of the hardcover 1s t edition 1977
© 1977 Plenum Press, New York
A Division of Plenum Publishing Corporation
227 West 17th Street, New York, N.Y. 10011
All rights reserved
No part of this book may be reproduced, stored in a retrieval system, or transmitted,
in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording, or otherwise, without written permission from the Publisher
Preface to Part A
This volume is intended to serve as an advanced text in organic chemistry and is
aimed at developing a deeper understanding of the structure of organic compounds
and the mechanisms of organic reactions. The text assumes introductory courses in
organic chemistry and in physical chemistry. The first three chapters consider three
fundamental aspects of the structure of organic molecules: bondirfg, stereochemis
try, and conformation. Chapter 4 is an overview of the methods that have been used
to probe details of organic reaction mechanisms. The remaining chapters are
organized on the basis of fundamental mechanistic patterns, although we return to
the topic of structure in Chapter 9, in which aromatic molecules are considered. At
Virginia, we have used this material in a course that serves third- and fourth-year
undergraduate chemistry majors and beginning graduate students.
By the use of extensive references and referenced problems from the literature,
we hope to provide an opportunity for the student to delve into the research
literature. Considerable numerical data are included with the intent that the student
can supplement a qualitative understanding of the role that substituents and other
structural features play in organic reactions with some grasp of the magnitude of such
effects. A considerable amount of this material is presented with a minimum of
commentary in schemes and tables. Much of organic chemistry, however, resists
interpretation in terms of a single variable. Often, several factors may operate in
different directions to influence rate or equilibria or both, and it may not be possible
to make consistently correct interpretations by inspection. Caution also needs to be
exercised in attempts at rationalizing small differences in rate or equilibria or both.
We recommend that instructors and students use these schemes and tables as
working outlines for further discussion.
We have tried to emphasize the teaching of concepts in our development and
treatment of the material. This emphasis of concepts is often best done by referring
the reader to review articles, and sometimes produces the unfortunate result of
failing to credit important contributions to their original source. To our colleagues
v
VI whose work fell into this category, we extend our apologies and request their
understanding of our attempts to produce a working text, rather than to review the
PREFACE TO
PART A historical development of various concepts and techniques.
This volume is a companion to Part B, Reactions and Synthesis. Part B
emphasizes the synthetically important organic reactions. It adds some further
mechanistic information, but is aimed primarily at introducing to students the
available repertoire of organic reactions and providing an opportunity to develop a
background in synthetic methodology.
We believe that Parts A and B used sequentially as texts in a one-year advanced
course will prepare the student to turn to the extensive review and monograph
literature and to the primary journals with a thorough exposure to both the
mechanistic and synthetic areas of organic chemistry.
Francis A. Carey
Richard J. Sundberg
Charlottesville, Virginia
Contents of Part A
List of Figures Xlll
List of Tables xvii
List of Schemes xxi
Contents of Part B xxiii
Chapter 1. Chemical Bonding and Molecular Structure 1
Introduction . . . . . . . . . . . . . . . 1
1.1. Valence-Bond Approach to Chemical Bonding 2
1.2. Bond Energies, Lengths, and Dipoles 10
1.3. Molecular Orbital Theory 15
1.4. Hiickel Molecular Orbital Theory 26
General References 32
Problems 32
Chapter 2. Stereochemical Principles 39
Introduction . . . . . . . 39
2.1. Enantiomeric Relationships 40
2.2. Diastereomeric Relationships 45
2.3. Dynamic Stereochemistry. 53
2.4. Prochiral Relationships 61
General References 66
Problems .... 66
Chapter 3. Conformational and Other Steric Effects 71
Introduction . . . . . . . . . . . 71
3.1. Steric Strain and Molecular Mechanics 72
3.2. Conformations of Acyclic Molecules . 78
Vlll 3.3. Conformations of Cyclohexane Derivatives . 83
3.4. Carbocyclic Rings Other Than Six-Membered 94
CONTENTS OF
PART A 3.5. Heterocyclic Conformational Analysis . . . 98
3.6. Molecular Orbital Methods Applied to Conformational Analysis 103
3.7. Conformational Effects on Reactivity 107
3.8. Other Steric Effects on Reactivity 111
General References 119
Problems .... 119
Chapter 4. Study and Description of Organic Reaction Mechanisms 125
Introduction . . . . 125
4.1. Thermodynamic Data .............. . 125
4.2. Kinetic Data . . . . . . . . . . . . . . . . . . . 127
4.3. Substituent Effects and Linear Free-Energy Relationships 139
4.4. Isotope Effe<;ts . . . . . . . . . . . . 149
4.5. Characterization of Reaction Intermediates 152
4.6. Catalysis ............. . 154
4.7. Solvent Effects . . . . . . . . . . . . 158
4.8. Basic Mechanistic Concepts: Kinetic Versus Thermodynamic
Control, Hammond's Postulate, the Curtin-Hammett Principle 163
4.9. Isotopes in Labeling Experiments 170
4.10. Stereochemistry 171
General References 172
Problems .... 173
Chapter 5. Nucleophilic Substitution 183
Introduction . . . . . . . . . . . . . . . . . . . . 183
5.1. The Limiting Cases-Substitution by the Ionization (SN1)
Mechanism . . . . . . . . . . . . . . . . . . . . . 184
5.2. The Limiting Cases-Substitution by the Direct Displacement (SN2)
Mechanism .......... 187
5.3. Alternative Mechanistic Hypotheses 190
5.4. Carbonium Ions 195
5.5. Nucleophilicity . . . . . . . . . 206
5.6. Leaving-Group Effects ..... 212
5.7. Steric and Other Substituent Effects on Substitution and Ionization
Rates . . . . . . . . . . . . . . . . . . . . . . . . 215
5.8. Stereochemistry of Nucleophilic Substitution ....... 219
5.9. Secondary Kinetic Isotope Effects in Substitution Mechanisms 227
5.10. Neighboring-GroupParticipation . . . . . . . . . . . . 229
5.11. Carbonium Ion Rearrangements ............ 236
5.12. Nonclassical Carbonium Ions and the Norbornyl Cation Problem 242
5.13. Synthetic Applications of Nucleophilic Substitution Reactions 249
General References 257
Problems .... 257
Chapter 6. Polar Addition and Elimination Reactions 265 IX
Introduction . . . . . . . . . . . . 265 CONTENTS OF
PART A
6.1. Addition of Hydrogen Halides to Alkenes 266
6.2. Acid-Catalyzed Hydration of Alkenes 271
6.3. Addition of Halogens . . . . . . . 272
6.4. TheE2,El,andElcbMechanisms .. 278
6.5. Orientation Effects in Elimination Reactions 282
6.6. Stereochemistry of E2 Elimination Reactions 286
6.7. Dehydration of Alcohols . . . . . . 290
6.8. Eliminations Not Involving C-H Bonds 291
General References 294
Problems .... 294
Chapter 7. Carbanions and Other Nucleophilic Carbon Species 299
Introduction . . . . . . . . . . . . . 299
7.1. Acidity of Hydrocarbons . . . . . . . . 299
7.2. Carbanions Stabilized by Functional Groups 307
7.3. Enols and Enamines 315
General References 319
Problems .... 319
Chapter 8. Reactions of Carbonyl Compounds 325
Introduction . . . . . . . . . . . . . . . . . . . . . 325
8.1. Hydration and Addition of Alcohols to Aldehydes and Ketones 326
8.2. Addition-Elimination Reactions of Ketones and Aldehydes 329
8.3. Reactivity of Carbonyl Compounds toward Addition 334
8.4. Ester Hydrolysis and Related Reactions ..... . 335
8.5. Amide Hydrolysis .............. . 341
8.6. Acylation of Nucleophilic Oxygen and Nitrogen Groups 343
8.7. Intramolecular Catalysis 347
General References 352
Problems 352
Chapter 9. Aromaticity and Electrophilic Aromatic Substitution 361
9.1. Aromaticity . . . . . . . . . . 361
9.1.1. The Concept of Aromaticity 361
9.1.2. TheAnnulenes ..... . 365
9.1.3. Aromaticity in Charged Rings 372
9.1.4. Fused-RingSystems 376
9.1.5. Homoaromaticity . . . . . 383
9.2. Electrophilic Aromatic Substitution Reactions 385
9.3. Structure-Reactivity Relationships 391
9.4. Specific Substitution Mechanisms 400
9.4.1. Nitration ...... . 400
x 9.4.2. Halogenation ............. . 404
9.4.3. Protonation and Hydrogen Exchange ... . 408
CONTENTS OF
PART A 9.4.4. Friedel-Crafts Alkylation and Related Reactions 410
9.4.5. Friedel-Crafts Acylation and Related Reactions 412
9.4.6. Coupling with Diazonium Compounds . . . . 414
9.4.7. Substitution of Groups Other Than Hydrogen . 415
9.5. Theoretical Treatments of Aromatic Substitution Reactions 417
General References 419
Problems .... 419
Chapter 10. Concerted Reactions 425
Introduction . . . . . . 425
10.1. Electrocyc1ic Reactions 426
10.2. SigmatropicRearrangements 439
10.3. Cyc1oaddition and Cyc1oelimination Reactions 449
General References 457
Problems .... 458
Chapter 11. Photochemistry 465
11.1. General Principles ................. 465
11.2. Orbital Symmetry Considerations Related to Photochemical
Reactions . . . . . . . . . . . . 470
11. 3. Photochemistry of Carbonyl Groups . . 474
11.4. Photochemistry of Alkenes and Dienes . 483
11.5. Photochemistry of Aromatic Compounds 492
General References 494
Problems 494
Chapter 12. Free-Radical Reactions 501
12.1. Generation and Characterization of Free Radicals 501
12.1.1. Background ........... . 501
12.1.2. Stable Free Radicals ........ . 502
12.1.3. Direct Detection of Radical Intermediates 504
12.1.4. Sources of Free Radicals ...... . 510
12.1.5. Structural and Stereochemical Properties of Radical
Intermediates . . . . . . . . . . . . . . . . 512
12.1.6. ChargedRadicalSpecies .......... . 516
12.2. Characteristics of Reaction Mechanisms Involving Radical
Intermediates . . . . . . . . . . . . . . . . 519
12.2.1. Kinetic Characteristics of Chain Reactions 519
12.2.2. Structure-Reactivity Relationships 522
12.3. Free-Radical Substitution Reactions 527
12.3.1. Halogenation 527
12.3.2. Oxidation 531