Advanced Organic FOURTH. Part A: Structure and Mechanisms

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1 Advanced Organic FOURTH Chemistry EDITION Part A: Structure and Mechanisms

2 Advanced Organic Chemistry PART A: Structure and Mechanisms PART B: Reactions and Synthesis

3 Advanced Organic Chemistry FOURTH EDITION Part A: Structure and Mechanisms FRANCIS A. CAREY and RICHARD J. SUNDBERG University of Virginia Charlottesville, Virginia Kluwer Academic Publishers New York, Boston, Dordrecht, London, Moscow

4 ebook ISBN: Print ISBN: Kluwer Academic Publishers New York, Boston, Dordrecht, London, Moscow Print 2000 Kluwer Academic Publishers New York All rights reserved No part of this ebook may be reproduced or transmitted in any form or by any means, electronic, mechanical, recording, or otherwise, without written consent from the Publisher Created in the United States of America Visit Kluwer Online at: and Kluwer's ebookstore at:

5 Preface to the Fourth Edition The goal of this text is to build on the foundation of introductory organic chemistry to provide students and other readers a deeper understanding of structure and mechanism and the relationships between them. We have provided speci c data and examples with which to illustrate the general principles that are discussed. Our purpose is to solidify the student's understanding of the basic concepts,but also to illustrate the way speci c structural changes in uence mechanism and reactivity. The rst three chapters discuss fundamental bonding theory,stereochemistry,and conformation,respectively. Chapter 4 discusses the means of study and description of reaction mechanisms. Chapter 9 focuses on aromaticity and aromatic stabilization and can be used at an earlier stage of a course if an instructor desires to do so. The other chapters discuss speci c mechanistic types,including nucleophilic substitution,polar additions and eliminations,carbon acids and enolates,carbonyl chemistry,aromatic substitution, concerted reactions,free-radical reactions,and photochemistry. Both the language of valence bond theory and of molecular orbital theory are used in discussing structural effects on reactivity and mechanism. Our intent is to illustrate both approaches to interpretation. A decade has passed since the publication of the Third Edition. That decade has seen signi cant developments in areas covered by the text. Perhaps most noteworthy has been the application of computational methods to a much wider range of problems of structure and mechanism. We have updated the description of computational methods and have included examples throughout the text of application of computational methods to speci c reactions. References to the primary literature are provided for speci c issues of structure, reactivity,and mechanism. These have been chosen to illustrate the topic of discussion and, of course,cannot be comprehensive. The examples and references chosen do not imply any priority of concept or publication. References to general reviews which can provide a broader coverage of the various topics are usually given. The problems at the end of each chapter represent application of concepts to new structures and circumstances,rather than review of material explicitly presented in the text. The level of dif culty is similar to that of earlier editions,and we expect that many will present a considerable challenge to students. Some new problems have been added in this v

6 vi PREFACE TO THE FOURTH EDITION edition. References to the literature material upon which the problems are based are given at the end of the book. The companion volume,part B,has also been revised to re ect the continuing development of synthetic methodology. Part B emphasizes synthetic application of organic reactions. We believe that the material in Part A and Part B will provide advanced undergraduate and beginning graduate students with a background which will permit them to understand,analyze,and apply the primary and review literature in organic chemistry. We hope that this new edition will continue to serve students and teachers in fostering both an understanding of the structural and mechanistic foundations of organic chemistry and a broad knowledge of the most fundamental reaction types in organic chemistry. We welcome comments and suggestions which can improve the text or correct errors. Charlottesville, Virginia F. A. Carey R. J. Sundberg

7 Contents of Part A Chapter 1. Chemical Bonding and Structure Valence Bond Description of Chemical Bonding Orbital Hybridization Resonance Bond Energy,Polarity,and Polarizability Bond Energies Electronegativity and Polarity PolarizabilityÐHardness and Softness Molecular Orbital Theory and Methods HuÈckel Molecular Orbital Theory Qualitative Application of Molecular Orbital Theory Application of Molecular Orbital Theory to Reactivity Interactions between s and p SystemsÐHyperconjugation Other Quantitative Descriptions of Molecular Structure Atoms in Molecules Electron Density Functionals Modern Valence Bond Approaches General References Problems Chapter 2. Principles of Stereochemistry Enantiomeric Relationships Diastereomeric Relationships Stereochemistry of Reactions Prochiral Relationships vii

8 viii CONTENTS OF PART A General References Problems Chapter 3. Conformational, Steric, and Stereoelectronic Effects Strain and Molecular Mechanics Conformations of Acyclic Molecules Conformations of Cyclohexane Derivatives Carbocyclic Rings Other Than Six-Membered The Effect of Heteroatoms on Conformational Equilibria The Anomeric Effect Conformational Effects on Reactivity Angle Strain and Its Effect on Reactivity Relationships between Ring Size and Rate of Cyclization Torsional and Stereoelectronic Effects on Reactivity General References Problems Chapter 4. Study and Description of Organic Reaction Mechanismns Thermodynamic Data Kinetic Data Substituent Effects and Linear Free-Energy Relationships Basic Mechanistic Concepts: Kinetic versus Thermodynamic Control, Hammond's Postulate,the Curtin±Hammett Principle Kinetic versus Thermodynamic Control Hammond's Postulate The Curtin±Hammett Principle Isotope Effects Isotopes in Labeling Experiments Characterization of Reaction Intermediates Catalysis by Brùnsted Acids and Bases Lewis Acid Catalysis Solvent Effects Substituent Effects in the Gas Phase Stereochemistry Conclusion General References Problems Chapter 5. Nucleophilic Substitution The Limiting CasesÐSubstitution by the Ionization S N 1) Mechanism The Limiting CasesÐSubstitution by the Direct Displacement S N 2) Mechanism Detailed Mechanistic Description and Borderline Mechanisms

9 5.4. Carbocations Nucleophilicity and Solvent Effects Leaving-Group Effects Steric and Strain Effects on Substitution and Ionization Rates Effects of Conjugation on Reactivity Stereochemistry of Nucleophilic Substitution Neighboring-Group Participation Mechanism of Rearrangements of Carbocations The Norbornyl Cation and Other Nonclassical Carbocations General References Problems ix CONTENTS OF PART A Chapter 6. Polar Addition and Elimination Reactions Addition of Hydrogen Halides to Alkenes Acid-Catalyzed Hydration and Related Addition Reactions Addition of Halogens Electrophilic Additions Involving Metal Ions Additions to Alkynes and Allenes The E2,E1,and E1cb Mechanisms Regiochemistry of Elimination Reactions Stereochemistry of E2 Elimination Reactions Dehydration of Alcohols Eliminations Not Involving C H Bonds General References Problems Chapter 7. Carbanions and Other Nucleophilic Carbon Species Acidity of Hydrocarbons Carbanions Stabilized by Functional Groups Enols and Enamines Carbanions as Nucleophiles in S N 2 Reactions General References Problems Chapter 8. Reactions of Carbonyl Compounds Hydration and Addition of Alcohols to Aldehydes and Ketones Addition±Elimination Reactions of Ketones and Aldehydes Addition of Carbon Nucleophiles to Carbonyl Groups Reactivity of Carbonyl Compounds toward Addition Ester Hydrolysis Aminolysis of Esters Amide Hydrolysis Acylation of Nucleophilic Oxygen and Nitrogen Groups

10 x CONTENTS OF PART A 8.9. Intramolecular Catalysis General References Problems Chapter 9. Aromaticity The Concept of Aromaticity The Annulenes Aromaticity in Charged Rings Homoaromaticity Fused-Ring Systems Heterocyclic Rings General References Problems Chapter 10. Aromatic Substitution Electrophilic Aromatic Substitution Reactions Structure±Reactivity Relationships Reactivity of Polycyclic and Heteroaromatic Compounds Speci c Substitution Mechanisms Nitration Halogenation Protonation and Hydrogen Exchange Friedel±Crafts Alkylation and Related Reactions Friedel±Crafts Acylation and Related Reactions Coupling with Diazonium Compounds Substitution of Groups Other Than Hydrogen Nucleophilic Aromatic Substitution by the Addition±Elimination Mechanism Nucleophilic Aromatic Substitution by the Elimination±Addition Mechanism General References Problems Chapter 11. Concerted Pericyclic Reactions Electrocyclic Reactions Sigmatropic Rearrangements Cycloaddition Reactions General References Problems Chapter 12. Free-Radical Reactions Generation and Characterization of Free Radicals

11 Background Stable and Persistent Free Radicals Direct Detection of Radical Intermediates Sources of Free Radicals Structural and Stereochemical Properties of Radical Intermediates Charged Radical Species Characteristics of Reaction Mechanisms Involving Radical Intermediates Kinetic Characteristics of Chain Reactions Structure±Reactivity Relationships Free-Radical Substitution Reactions Halogenation Oxidation Free-Radical Addition Reactions Addition of Hydrogen Halides Addition of Halomethanes Addition of Other Carbon Radicals Addition of Thiols and Thiocarboxylic Acids Halogen,Sulfur,and Selenium Group Transfer Reactions Intramolecular Free-Radical Reactions Rearrangement and Fragmentation Reactions of Free Radicals Rearrangement Reactions Fragmentation Electron-Transfer Reactions Involving Transition-Metal Ions S RN 1 Substitution Processes General References Problems xi CONTENTS OF PART A Chapter 13. Photochemistry General Principles Orbital Symmetry Considerations Related to Photochemical Reactions Photochemistry of Carbonyl Compounds Photochemistry of Alkenes and Dienes Photochemistry of Aromatic Compounds General References Problems References to Problems Index

12 Contents of Part B Chapter 1. Alkylation of Nucleophilic Carbon. Enolates and Enamines Chapter 2. Reactions of Carbon Nucleophiles with Carbonyl Groups Chapter 3. Functional Group Interconversion by Nucleophilic Substitution Chapter 4. Electrophilic Additions to Carbon-Carbon Multiple Bonds Chapter 5. Reduction of Carbonyl and Other Functional Groups Chapter 6. Cycloaddition, Unimolecular Rearrangements, and Thermal Eliminations Chapter 7. Organometallic Compounds of the Group I and II Metals Chapter 8. Reactions Involving the Transition Metals Chapter 9. Carbon-Carbon Bond-Forming Reactions of Compounds of Boron, Silicon, and Tin Chapter 10. Reactions Involving Carbocations, Carbenes, and Radicals as Reactive Intermediates Chapter 11. Aromatic Substitution Reactions Chapter 12. Oxidations Chapter 13. Planning and Execution of Multistep Syntheses xii