Advanced Organic • t SECOND Che m IS ry EDITION Part A: Structure and Mechanisms Advanced Organic Chemistry PART A: Structure and Mechanisms PART B: Reactions and Synthesis Advanced Organic SECOND Chemistry EDITION Part A: Structure ,and Mechanisms FRANCIS A. CAREY and RICHARD J. SUNDBERG University of Virginia Charlottesville, Virginia SPRINGER SCIENCE+BUSINESS MEDIA, LLC Library of Congress Cataloging in Publication Data Carey, Francis A., 1937- Advanced organic chemistry. Includes bibliographical references and index. Contents: pt. A. Structure and mechanisms-pt. B. Reactions and synthesis. I. Chemistry, Organic. I. Sundberg, Richard J., 1938- . II. Title. QD251.2.C36 1984 547 84-8229 ISBN 978-1-4757-1145-5 ISBN 978-1-4757-1143-1 (eBook) DOI 10.1007/978-1-4757-1143-1 © 1984 Springer Science+B usiness Media New York Originally published by Plenum Press, New York in 1984 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 the Second Edition The purpose of this edition is the same as that of the first edition, that is, to provide a deeper understanding of the structures of organic compounds and the mechanisms of organic reactions. The level is aimed at advanced undergraduates and beginning graduate students. Our goal is to solidify the student's understanding of basic concepts provided in an introduction to organic chemistry and to fill in much more information and detail, including quantitative information, than can be presented in the first course in organic chemistry. The first three chapters consider the fundamental topics of bonding theory, stereochemistry, and conformation. Chapter 4 discusses the techniques that are used to study and characterize reaction mechanisms. The remaining chapters consider basic reaction types with a broad coverage of substituent effects and stereochemistry being provided so that each reaction can be described in good, if not entirely complete, detail. The organization is very similar to the first edition with only a relative shift in emphasis having been made. The major change is the more general application of qualitative molecular orbital theory in presenting the structural basis of substituent and stereoelectronic effects. The primary research literature now uses molecular orbital approaches very widely, while resonance theory serves as the primary tool for explanation of structural and substituent effects at the introductory level. Our intention is to illustrate the use of both types of interpretation, with the goal of facilitating the student's ability to understand and apply the molecular orbital concepts now widely in use. As in the first edition, the specific reactions discussed have been chosen to illustrate a point and no effort has been made to trace the origin of a particular explanation or observation. Thus references to a particular example do not imply any indication of priority. We have also tried to cite references to reviews which will give readers the opportunity to consider specific reactions from a much more comprehensive and detailed point of view than is possible in this text. v Vl Some of the problems are new. The general level is similar to that in the first edition and it is expected that most of the problems will present a considerable PREFACE degree of challenge to the typical student, since most represent application of the ideas presented in the text to different systems and circumstances, rather than review or repetition of the material which was explicitly presented in the text. References to the literature material upon which the problems are based are given at the end of the book for nearly all the problems. The companion volume, Part B, has also been substantially revised to reflect the major developments in synthetic procedures that have taken place since the initial material was prepared. Part B extends the material of Part A with particular emphasis on the synthetic application of organic reactions. We believe that the material in Parts A and B can serve to prepare students to assimilate and apply the extensive primary and review literature of organic chemistry. We thank colleagues who have provided comments and encouragement regard- ing the first edition. We hope that we will continue to receive suggestions concerning the organization and presentation of the material and also information concerning errors and omissions. F. A. Carey R. J. Sundberg Charlottesville, Virginia January 1983 Contents of Part A Chapter 1. Chemical Bonding and Molecular Structure 1 1.1. Valence Bond Approach to Chemical Bonding 2 1.2. Bond Energies, Lengths, and Dipoles . . . . 11 1.3. Molecular Orbital Methods . . . . . . . . 17 1.4. Qualitative Application of Molecular Orbital Theory 23 1.5. Hiickel Molecular Orbital Theory . . . . . . . . 37 1.6. PMO Theory . . . . . . . . . . . . . . . . 44 1. 7. Interaction between 1T and u Systems-Hyperconjugation 51 General References 55 Problems .... 55 Chapter 2. Stereochemical Principles 61 2.1. Enantiomeric Relationships 62 2.2. Diastereomeric Relationships 69 2.3. Dynamic Stereochemistry 76 2.4. Prochiral Relationships 85 General References 91 Problems .... 92 Chapter 3. Conformational, Steric, and Stereoelectronic Effects 99 3.1. Steric Strain and Molecular Mechanics 100 3.2. Conformations of Acyclic Molecules 107 3.3. Conformations of Cyclohexane Derivatives 111 3.4. Carbocyclic Rings Other Than Six Membered 123 3.5. Conformational Analysis of Heterocyclic Molecules 128 3.6. Molecular Orbital Methods Applied to Conformational Analysis 133 Vll vm 3. 7. Conformational Effects on Reactivity . .. . . . . . . . . 137 3.8. Angle Strain and Its Effect on Reactivity . . . . . . . . 141 CONTENTS OF PART A 3.9. Relationships between Ring Size and Facility of Ring Closure 147 3.1 0. Torsional Strain and Related Stereoelectronic Effects 150 General References 154 Problems . . . . 154 Chapter 4. Study and Description of Organic Reaction Mechanisms 161 4.1. Thermodynamic Data 161 4.2. Kinetic Data . . . . . . . . . . . . . . . . . . . . 165 4.3. Substituent Effects and Linear Free-Energy Relationships 179 4.4. Isotope Effects 190 4.5. Characterization of Reaction Intermediates 194 4.6. Catalysis . . . . . . . . . . . 197 4. 7. Solvent Effects . . . . . . . . . 202 4.8. Structural Effects in the Gas Phase 209 4.9. Basic Mechanistic Concepts: Kinetic Versus Thermodynamic Control, Hammond's Postulate, the Curtin-Hammett Principle 212 4.10. Isotopes in Labeling Experiments 220 4.11. Stereochemistry 221 General References 223 Problems . . . . 224 Chapter 5. Nucleophilic Substitution 235 5.1. The Limiting Cases-Substitution by the Ionization (SN 1) Mechanism 238 5.2. The Limiting Cases-Substitution by the Direct Displacement (SN2) Mechanism 240 5.3. Detailed Mechanistic Descriptions and Borderline Mechanisms 243 5.4. Carbonium Ions . . . . . . . . 248 5.5. Nucleophilicity and Solvent Effects 263 5.6. Leaving-Group Effects . . . . . 271 5. 7. Steric and Other Substituent Effects on Substitution and Ionization Rates . . . . . . . . . . . . . . . . . . . . . . . . . 274 5.8. Stereochemistry of Nucleophilic Substitution . . . . . . . . 278 5.9. Secondary Kinetic Isotope Effects in Substitution Mechanisms 287 5.10. Neighboring-Group Participation 289 5.11. Carbonium Ion Rearrangements 298 5.12. The Norbornyl Cation 304 General References 312 Problems . . . . 313 Chapter 6. Polar Addition and Elimination Reactions 323 lX CONTENTS OF 6.1. Addition of Hydrogen Halides to Alkenes ...... . 324 PART A 6.2. Acid-Catalyzed Hydration and Related Addition Reactions 330 6.3. Addition of Halogens . . . . 333 6.4. Additions Involving Metal Ions . . 339 6.5. Additions to Acetylenes . . . . . 341 6.6. The E2, E1, and E1cb Mechanisms 345 6. 7. Orientation Effects in Elimination Reactions 351 6.8. Stereochemistry of E2 Elimination Reactions 356 6.9. Dehydration of Alcohols . . .... 361 6.10. Eliminations Not Involving C-H Bonds 362 General References 365 Problems .... 366 Chapter 7. Carbanions and Other Nucleophilic Carbon Species 0 •• 0 373 7 .1. Acidity of Hydrocarbons . . . . . . . . 373 7.2. Carbanions Stabilized by Functional Groups 382 7.3. Enols and Enamines 390 General References 395 Problems .... 396 Chapter 8. Reactions of Carbonyl Compounds . . . . . . . . . . 403 8.1. Hydration and Addition of Alcohols to Aldehydes and Ketones 404 8.2. Addition-Elimination Reactions of Ketones and Aldehydes 411 8.3. Reactivity of Carbonyl Compounds toward Addition 417 8.4. Ester Hydrolysis 421 8.5. Aminolysis of Esters 426 8.6. Amide Hydrolysis 431 8. 7. Acylation of Nucleophilic Oxygen and Nitrogen Groups 433 8.8. Intramolecular Catalysis 437 General References 444 Problems . . . . 444 Chapter 9. Aromaticity and Electrophilic Aromatic Substitution 0 ••• 455 9.1. Aromaticity . . . . . . . . . . 455 9 .1.1. The Concept of Aromaticity 455 9.1.2. The Annulenes ..... 460 9.1.3. Aromaticity in Charged Rings 468 9.1.4. Homoaromaticity 472 9.1.5. Fused-Ring Systems 475