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Advanced Organic Ch · t THIRD emlS ry EDITION

Part A: Structure and Mechanisms

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

Advanced Organic Chemistry THIRD

EDITION

Part A: Structure and Mechanisms

FRANCIS A. CAREY and RICHARD J. SUNDBERG University of Virginia Charlottesville, Virginia

PLENUM PRESS • NEW YORK AND LONDON

Library of Congress Cataloglng-In-Publlcatlon Data

Carey. Francis A .• 1937-Advanced organic chellstry I Francis A. Carey and Richard J.

Sundberg. -- 3rd ed. p. c ••

Includes bibliographical references. CD~tents: pt. A. Structure and lechanlsNs.

ISBN-13: 978-0-306-43447-1 e-ISBN-13: 978-1-4613-9795-3

001: 10.1007/978-1-4613-9795-3

1. Che.lstry. OrganiC. II. T1tle. QD251.2.C36 ·1990 547--dc20

First Printing-April 1990 Second Printing-October 1991

I. Sundberg. Richard J .• 1938-

© 1990, 1984, 1977 Plenum Press, New York A Division of Plenum Publishing Corporation 233 Spring Street, New York. N.Y. 10013

All rights reserved

90-6851 CIP

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 Third Edition

The purpose of this edition, like that of the earlier ones, is to provide the basis for 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 goals are to solidify the student's understanding of basic concepts provided by an introduction to organic chemistry and to present 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 topi~s of bonding theory, stereochemistry, and conformation. Chapter 4 discusses the techniques that are used to study and characterize reaction mechanisms. Chapter 9 focuses on aromaticity and the structural basis of aromatic stabilization. The remaining chapters consider basic reaction types, including substituent effects and stereochemistry. As compared to the earlier editions, there has been a modest degree of reorganization. The emergence of free-radical reactions in synthesis has led to the inclusion of certain aspects of free-radical chemistry in Part B. The revised chapter, Chapter 12, emphasizes the distinctive mechanistic and kinetic aspects of free-radical reactions. The synthetic applications will be considered in Part B. We have also split the topics of aromaticity and the reactions of aromatic compounds into two separate chapters, Chapters 9 and 10. This may facilitate use of Chapter 9, which deals with the nature of aromaticity, at an earlier stage if an instructor so desires.

Both the language of valence bond theory and resonance and that of molecular orbital theory are used in the discussion of structural effects on reactivity. 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 both of these viewpoints of structure. Nearly all reaction types and concepts are illustrated by specific examples from the chemical literature. Such examples, of course, cannot provide breadth of coverage, and those that are cited have been selected merely to illustrate the mechanism or interpretation. Such illustrations are not meant to suggest any

v

VI

PREFACE

priority of the specific example which has been selected. Whenever possible, references to reviews which can provide a broader coverage of the topic are given.

Some new problems have been added. The general level is similar to that of the earlier editions, and we expect many of the problems will present a considerable challenge to the student. Most represent applications of concepts to new systems and circumstances, rather than review of material 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 neady all problems.

The companion volume, Part B, has been revised to reflect the continuing development and evolution of synthetic practice. Part B emphasizes the synthetic applications of organic reactions. We believe that the material in Parts A and B can provide a level of preparation which will permit the student to assimilate and apply the primary and review literature of organic chemistry.

During the preparation of the third edition, F.A.C. has been involved in other writing endeavors, and the primary responsibility for new errors or omission of new results rests with R.J.S. We hope that this text will continue to serve students in fostering an understanding of organic chemistry. We continue to welcome comments and suggestions from colleagues which can improve the treatment of material in this text.

F. A. Carey R. J. Sundberg

Charlottesville, Virginia

Contents of Part A

Chapter 1. Chemical Bonding and Structure . . . . .

1.1. Valence Bond Approach to Chemical Bonding 1.2. Bond Energies, Lengths, and Dipoles .... 1.3. Molecular Orbital Theory and Methods 1.4. Qualitative Application of Molecular Orbital Theory 1.5. Huckel Molecular Orbital Theory . . . . . . . . 1.6. Perturbation Molecular Orbital Theory ..... . 1.7. Interactions between u and 'TT Systems-Hyperconjugation

General References Problems ....

Chapter 2. Stereochemical Principles

2.1. Enantiomeric Relationships .... 2.2. Diastereomeric Relationships . . . . 2.3. Stereochemistry of Dynamic Processes 2.4. Prochiral Relationships


Chapter 3. Conformational, Steric, and Stereoelectronic Effects

3.1. Steric Strain and Molecular Mechanics 3.2. Conformations of Acyclic Molecules 3.3. Conformations of Cyclohexane Derivatives 3.4. Carbocyclic Rings Other Than Six-Membered

vii

1

2 11 20 27 37 46 54 59 59

67

68 75 88 98

108 108

117

118 124 130 141

viii

CONTENTS OF PART A

3.5. The Effect of Heteroatoms on Conformational Equilibria 3.6. Molecular Orbital Methods Applied to Conformational Analysis 3.7. Conformational Effects on Reactivity ......... . 3.8. Angle Strain and Its Effect on Reactivity . . . . . . . . . 3.9. Relationships between Ring Size and Facility of Ring Closure 3.10. Torsional and Stereoelectronic Effects on Reactivity

General References .. Problems .....

Chapter 4. Study and Description of Organic Reaction Mechanisms

4.1. Thermodynamic Data 4.2. Kinetic Data . . . .

144 151 152 157 163 167 172 172

179

180 183

4.3. Substituent Effects and Linear Free-Energy Relationships 196 4.4. Basic Mechanistic Concepts: Kinetic versus Thermodynamic

Control, Hammond's Postulate, and the Curtin-Hammett Principle 209 4.4.1. Kinetic versus Thermodynamic Control 209 4.4.2. Hammond's Postulate . . . . 211 4.4.3. The Curtin-Hammett Principle 215

4.5. Isotope Effects .......... 216 4.6. Isotopes in Labeling Experiments . . 220 4.7. Characterization of Reaction Intermediates 221 4.8. Catalysis by Acids and Bases 4.9. Lewis Acid Catalysis .4.10. Solvent Effects 4.11. Structural Effects in the Gas Phase 4.12. Stereochemistry . . 4.13. Conclusion ....


Chapter 5. Nucleophilic Substitution . . . . . . . . . . . . .

5.1. The Limiting Cases-Substitution by the Ionization (SN 1)

223 229 232 239 242 244 244 245

257

Mechanism ........................ 258 5.2. The Limiting Cases-Substit~tion by the Direct Displacement (SN 2)

Mechanism .•.................... 261 5.3. Detailed Mechanistic Description and Borderline Mechanisms 264 5.4. Carbocations . . . . . . . . . . 270 5.5. Nucleophilicity and Solvent Effects 284 5.6. Leaving Group Effects . . . . . . 290 5.7. Steric and Strain Effects on Substitution and Ionization Rates 293 5.8. Substituent Effects on Reactivity ..... 5.9. Stereochemistry of Nucleophilic Substitution

296 297

5.10. Neighboring-Group Participation ....... . . . . . 5.11. Rearrangements of Carbocations ........... . 5.12. The Norbornyl Cation and Other Nonclassical Carbocations


Chapter 6. Polar Addition and Elimination Reactions

6.1. Addition of Hydrogen Halides to Alkenes 6.2. Acid-Catalyzed Hydration and Related Addition Reactions 6.3. Addition of Halogens 6.4. Electrophilic Additions Involving Metal Ions 6.5. Additions to Alkynes and Allenes 6.6. The E2, E1, and E1cb Mechanisms 6.7. Orientation Effects in Elimination Reactions 6.8. Stereochemistry of E2 Elimination Reactions 6.9. Dehydration of Alcohols 6.10. Eliminations Not Involving C-H Bonds

General References Problems

Chapter 7. Carbanions and Other Nucleophilic Carbon Species .....

7.1. Acidity of Hydrocarbons ........ . 7.2. Carbanions Stabilized by Functional Groups 7.3. Enols and Enamines ......... . 7.4. Carbanions as Nucleophiles in SN2 Reactions

General References Problems .............. .

305 313 319 328 328

341

342 348 351 359 361 368 373 377 383 384 389 389

397

397 407 416 423 430 431

Chapter 8. Reactions of Carbonyl Compounds . . . . . . . . . . . 439

8.1. Hydration and Addition of Alcohols to Aldehydes and Ketones 439 8.2. Addition-Elimination Reactions of Aldehydes and Ketones 447 8.3. Addition of Carbon Nucleophiles to Carbonyl Groups 453 8.4. Reactivity of Carbonyl Compounds toward Addition 462 8.5. Ester Hydrolysis 465 8.6. Aminolysis of Esters 470 8.7. Amide Hydrolysis . 473 8.8. Acylation of Nucleophilic Oxygen and Nitrogen Groups 475 8.9. Intramolecular Catalysis 479

General References 487 Problems .... 487

IX

CONTENTS OF PART A

x

CONTENTS OF PART A

Chapter 9. Aromaticity

9.1. The Concept of Aromaticity 9.2. The Annulenes 9.3. Aromaticity in Charged Rings 9.4. Homoaromaticity 9.5. Fused-Ring Systems 9.6. Heterocyclic Rings


Chapter 10. Aromatic Substitution ....... .

10.1 Electrophilic Aromatic Substitution Reactions 10.2. Structure-Reactivity Relationships 10.3. Reactivity of Polycyclic and Heteroaromatic Compounds 10.4. Specific Substitution Mechanisms

10.4.1. Nitration 10.4.2. Halogenation 10.4.3. Protonation and Hydrogen Exchange 10.4.4. Friedel-Crafts Alkylation and Related Reactions 10.4.5. Friedel-Crafts Acylation and Related Reactions 10.4.6. Coupling with Diazonium Compounds . . 10.4.7. Substitution of Groups Other than Hydrogen

10.5. Nucleophilic Aromatic Substitution by Addition-Elimination 10.6. Nucleophilic Aromatic Substitiution by the Elimination-Addition

Mechanism General References Problems

Chapter 11. Concerted Reactions

11.1 Electrocyclic Reactions 11.2. Sigmatropic Rearrangements 11.3. Cycloaddition Reactions


Chapter 12. Free-Radical Reactions

12.1. Generation and Characterization of Free Radicals 12.1.1. Background ........... .

499

499 503 513 518 521 531 532 532

539

539 546 557 561 561 565 569 570 573 576 577 579

583 587 587

595

596 609 625 640 640

651

651 651

12.1.2. Stable and Persistent Free Radicals 12.1.3. Direct Detection of Radical Intermediates 12.1.4. Sources of Free Radicals . . . . . . . 12.1.5. Structural and Stereochemical Properties of Radical

Intermediates . . . . . . . . . . . . . . . . 12.1.6. Charged Radical Species . . . . . . . . . . .

12.2. Characteristics of Reaction Mechanisms Involving Radical Intermediates ............... . 12.2.1. Kinetic Characteristics of Chain Reactions 12.2.2. Structure-Reactivity Relationships

12.3. Free-Radical Substitution Reactions 12.3.1. Halogenation . . . . . 12.3.2. Oxidation .....

12.4. Free-Radical Addition Reactions 12.4.1. Addition of Hydrogen Halides 12.4.2. Addition of Halomethanes 12.4.3. Addition of Other Carbon Radicals 12.4.4. Addition of Thiols and Thiocarboxylic Acids

12.5. Intramolecular Free-Radical Reactions ..... . 12.6. Rearrangement and Fragmentation Reactions of Free Radicals

12.6.1. Rearrangement Reactions .......... . 12.6.2. Fragmentation Reactions . . . . . . . . . . . .

12.7. Electron Transfer Reactions Involving Transition Metal Ions 12.8. SRN 1 Substitution Processes


Chapter 13. Photochemistry

13.1. General Principles ................ . 13.2. Orbital Symmetry Considerations Related to Photochemical

Reactions ............ . 13.3. Photochemistry of Carbonyl Compounds 13.4. Photochemistry of Alkenes and Dienes 13.5. Photochemistry of Aromatic Compounds


References for Problems

Index

652 Xl 655 660

CONTENTS OF PART A

664 668

671 671 674 688 688 693 695 695 698 700 701 701 704 704 706 709 712 719 719

729

.. 729

734 738 751 762 764 765

773

787

Contents of Part B

List of Figures

List of Tables

List of Schemes

Chapter 1. Alkylation of Nucleophilic Carbon. Enolates and Enamines

1.1. Generation of Carbanions by Deprotonation 1.2. Regioselectivity and Stereoselectivity in Enolate Formation 1.3. Other Means of Generating Enolates 1.4. Alkylation of Enolates 1.5. Generation and Alkylation of Dianions 1.6. Medium Effects in the Alkylation of Enolates 1.7. Oxygen versus Carbon as the Site of Alkylation 1.8. Alkylation of Aldehydes, Esters, Amides, and Nitriles 1.9. The Nitrogen Analogs of Enols and Enolates-Enamines and Imine

Anions 1.10. Alkylation of Carbon NucIeophiles by Conjugate Addition


Chapter 2. Reactions of Carbon Nucleophiles with Carbonyl Groups

2.1. Aldol Condensation 2.1.1. The General Mechanism 2.1.2. Mixed Aldol Condensations with Aromatic Aldehydes 2.1.3. Control of Regiochemistry and Stereochemistry of Mixed

Aldol Condensations of Aliphatic Aldehydes and Ketones

xiii

XIV

CONTENTS OF PART B

2.1.4. Intramolecular Aldol Condensations and the Robinson Annulation

2.2. Condensation Reactions of Imines and Iminium Ions 2.2.1. The Mannich Reaction 2.2.2. Amine-Catalyzed Condensation Reactions

2.3. Acylation of Carbanions 2.4. The Wittig and Related Reactions 2.5. Reactions of Carbonyl Compounds with a-Trimethylsilyl

Carbanions 2.6. Sulfur Ylides and Related Nucleophiles 2.7. Nucleophilic Addition-Cyclization


Chapter 3. Functional Group Interconversion by Nucleophilic Substitution

3.1. Conversion of Alcohols to Alkylating Agents 3.1.1. Sulfonate Esters 3.1.2. Halides

3.2. Introduction of Functional Groups by Nucleophilic Substitution at Saturated Carbon 3.2.1. General Solvent Effects 3.2.2. Nitriles 3.2.3. Azides 3.2.4. Alkylation of Amines and Amides 3.2.5. Oxygen Nucleophiles 3.2.6. Sulfur Nucleophiles 3.2.7. Phosphorus NUcleophiles 3.2.8. Summary of Nucleophilic Substitution at Saturated Carbon

3.3. Nucleophilic Cleavage of Carbon-Oxygen Bonds in Ethers and Esters

3.4. Interconversion of Carboxylic Acid Derivatives 3.4.1. Preparation of Reaction Reagents for Acylation 3.4.2. Preparation of Esters 3.4.3. Preparation of Amides Problems

Chapter 4. Electrophilic Additions to Carbon-Carbon Multiple Bonds

4.1. Addition of Hydrogen Halides 4.2. Hydration and Other Acid-Catalyzed Additions 4.3. Oxymercuration 4.4. Addition of Halogens to Alkenes 4.5. Electrophilic Sulfur and Selenium Reagents 4.6. Addition of Other Electrophilic Reagents 4.7. Electrophilic Substitution Alpha to Carbonyl Groups

4.8. Additions to Allenes and Alkynes 4.9. Addition at Double Bonds via Organoboranes

4.9.1. Hydroboration 4.9.2. Reactions of Organoboranes 4.9.3. Enantioselective Hydroboration 4.9.4. Hydroboration of Alkynes General References Problems

Chapter S. Reduction of Carbonyl and Other Functional Groups

5.1. Addition of Hydrogen 5.1.1. Catalytic Hydrogenation 5.1.2. Other Hydrogen-Transfer Reagents

5.2. Group III Hydride-Donor Reagents 5.2.1. Reduction of Carbonyl Compounds 5.2.2. Reduction of Other Functional Groups by Hydride Donors

5.3. Group IV Hydride Donors 5.4. Hydrogen Atom Donors 5.5. Dissolving-Metal Reductions

5.5.1. Addition of Hydrogen 5.5.2. Reductive Removal of Functional Groups 5.5.3. Reductive Carbon-Carbon Bond Formation

5.6. Reductive Deoxygenation of Carbonyl Groups General References Problems

Chapter 6. Cycioaddition, Unimolecular Rearrangements, and Thermal Eliminations

6.1. Cycloaddition Reactions 6.1.1. The Diels-Alder Reaction: General Features 6.1.2. The Diels-Alder Reaction: Dienophiles 6.1.3. The Diels-Alder Reaction: Dienes 6.1.4. Intramolecular Diels-Alder Reactions

6.2. Dipolar Cycloaddition Reactions 6.3. [2 + 2] Cycloadditions and Other Reactions Leading to

Cyclobutanes 6.4. Photochemical Cycloaddition Reactions 6.5. [3,3]-Sigmatropic Rearrangements: Cope and Claisen

Rearrangements 6.6. [2,3]-Sigmatropic Rearrangements 6.7. Ene Reactions 6.8. Unimolecular Thermal Elimination Reactions

6.8.1. Cheletropic Elimination 6.8.2. Decomposition of Cyclic Azo Compounds

xv

CONTLNTS OF PART B

XVl

CONTENTS OF PART B

6.8.3. f3-Eliminations Involving Cyclic Transition States General References Problems

Chapter 7. Organometallic Compounds of Group I and II Metals

7.1. Preparation and Properties of Organolithium and Organomagnesium Compounds

7.2. Reactions of Organolithium and Organomagnesium Compounds 7.2.1. Reactions with Alkylating Agents 7.2.2. Reactions with Carbonyl Compounds

7.3. Organic Derivatives of Group lIB Metals 7.3.1. Organozinc Compounds 7.3.2. Organocadmium Compounds 7.3.3. Organomercury Compounds

7.4. Organocerium Compounds General References Problems

Chapter 8. Reactions Involving the Transition Metals

8.1. Reactions Involving Organocopper Intermediates 8.2. Reactions Involving Organopalladium Intermediates 8.3. Reactions Involving Organonickel Compounds 8.4. Reactions Involving Rhodium, Iron, and Cobalt 8.5. Organometallic Compounds with 7T Bonding


Chapter 9. Carbon-Carbon Bond-Forming Reactions of Compounds of Boron, Silicon, and Tin

9.1. Organoboron Compounds 9.1.1. Synthesis of Organoboranes 9.1.2. Carbon-Carbon Bond-Forming Reactions

9.2. Organosilicon Compounds 9.2.1. Synthesis of Organosilanes 9.2.2. Carbon-Carbon Bond-Forming Reactions

9.3. Organotin Compounds 9.3.1. Synthesis of Organostannanes 9.3.2. Carbon-Carbon Bond-Forming Reactions General References Problems

Chapter 10, Reactions! Involving Highly Reactive Electron-Deficient Intermediates

10.1. Reactions Involving Carbocation Intermediates 10.1.1. Carbon-Carbon Bond-Formation Involving Carbocations 10.1.2. Rearrangements of Carbocations 10.1.3. Related Rearrangements 10.1.4. Fragmentation Reactions

10.2. Reactions Involving Carbenes and Nitrenes 10.2.1. Structure and Reactivity of Carbenes 10.2.2. Generation of Carbenes 10.2.3. Addition Reactions 10.2.4. Insertion Reactions 10.2.5. Rearrangement Reactions 10.2.6. Related Reactions 10.2.7. Nitrenes and .Related Intermediates 10.2.8. Rearrangements to Electron-Deficient Nitrogen

10.3. Reactions Involving Free-Radical Intermediates 10.3.1. Sources of Radical Intermediates 10.3.2. Introduction of Functionality by Radical Reactions 10.3.3. Addition Reactions of Radicals with Substituted Alkenes 10.3.4. Cyclization of Free-Radical Intermediates 10.3.5. Fragmentation and Rearrangement Reactions General References Problems

Chapter 11. Aromatic Substitution Reactions

11.1. Electrophilic Aromatic Substitution 11.1.1. Nitration 11.1.2. Halogenation 11.1.3. Friedel-Crafts Alkylations and Acylations 11.1.4. Electrophilic Metalation

11.2. Nucleophilic Aromatic Substitution 11.2.1. Aromatic Diazonium Ions as Synthetic Intermediates 11.2.2. Substitution by the Addition-Elimination Mechanism 11.2.3. Substitution'by the Elimination-Addition Mechanism 11.2.4. Copper-Catalyzed Reactions

11.3. Aromatic Radical Substitution Reactions 11.4. Substitution by the SRN 1 Mechanism

Problems

Chapter 12. Oxidations

12.1. Oxidation of Alcohols to Aldehydes, Ketones, or Carboxylic Acids 12.1.1. Transition Metal Oxidants 12.1.2. Other Oxidants

xvii

CONTENTS OF PART B

xviii

CONTENTS OF PART B

12.2. Addition of Oxygen at Carbon-Carbon Double Bonds 12.2.1. Transition Metal Oxidants 12.2.2. Epoxides from Alkenes and Peroxidic Reagents 12.2.3. Subsequent Transformations of Epoxides 12.2.4. Reactions of Alkenes with Singlet Oxygen

12.3. Cleavage of Carbon-Carbon Double Bonds 12.3.1. Transition Metal Oxidants 12.3.2. Ozonolysis

12.4. Selective Oxidative Cleavages at Other Functional Groups 12.4.1. Cleavage of Glycols 12.4.2. Oxidative Decarboxylation

12.5. Oxidation of Ketones and Aldehydes 12.5.1. Transition Metal Oxidants 12.5.2. Oxidation of Ketones and Aldehydes by Oxygen and

Peroxidic Compounds 12.5.3. Oxidation with Other Reagents

12.6. Allylic Oxidation 12.6.1. Transition Metal Oxidants 12.6.2. Other Oxidants

12.7. Oxidations at Unfunctionalized Carbon General References Problems

Chapter 13. Multistep Syntheses

13.1. Protective Groups 13.1.1. Hydroxyl-Protecting Groups 13.1.2. Amino-Protecting Groups 13.1.3. Carbonyl-Protecting Groups 13.1.4. Carboxy Acid-Protecting Groups

13.2. Synthetic Equivalent Groups 13.3. Synthetic Analysis and Planning 13.4. Control of Stereochemistry 13.5. Illustrative Syntheses

13.5.1. luvabione 13.5.2. Longifolene 13.5.3. Prelog-Djerassi Lactone 13.5.4. Aphidicolin General References Problems

References for Problems

Index

List of Tables

1.1. Dependence of s~ructure on hybridization of carbon 1.2. Bond lengths 1.3. Bond energies 1.4. Heterolytic bond dissociation energies for some C-Hand C-Cl bonds 1.5. Standard heats of formation of some hydrocarbons 1.6. Heats of hydrogenation of some alkenes 1.7. Atomic and group electronegativities 1.8. Bond and group dipoles for some organic functional groups 1.9. Acidity of substituted acetic acids 1.10. Hardness of some atoms, cations and anions 1.11. Deviations of calculated values from experimental dHf data for various

MO methods 1.12. Coefficients of wave functions calculated for methyl cation by the

CNDO/2 approximation 1.13. Calculated charge transfer and stabilization resulting from substituents on

the methyl cation 1.14. Calculated stabilization of methyl anion by substituents 1.15. Energy levels and coefficients for HMOs of 1,3,5-hexatriene 1.16. Stabilization resulting from conjugation of ethylene with substituents

2.1. Enantioselective reduction of 2-acetamidoacrylic acids by chiral phosphine complexes of rhodium

2.2. Examples of enantioselective reduction of acetophenone

3.1. Van der Waals radii of several atoms and groups 3.2. Composition-Equilibrium-Free-Energy Relationships 3.3. Correlation between intramolecular strain and activation energies for

dissociation of C-C bonds in substituted ethanes

xix

xx

LIST OF TABLES

3.4. 3.5.

3.6. 3.7. 3.8.

Rotational energy barriers of compounds of the type CH3-X Half-life for conformational inversion of cyclohexyl chloride at various temperatures Conformational free energies (-aGO) for substituent groups Strain energies of cycloalkanes Comparison of conformational free-energy values for substituents on tetrahydropyran, 1,3-dioxane, and 1,3-dithiane rings with those for cyclohexane

3.9. Strain energies in some alicyclic compounds 3.10. Relative stabilities of cis- and trans-cycloalkenes 3.11. Relative rates of cyclization of diethyl (w-bromoalkyl)malonate ester

anions as a function of ring size 3.12. Classification of ring-closure types 3.13. Comparison of the stereochemistry of reactions with bicyclo[2.2.1]heptene

and 7,7 -dimethylbicyclo[2.2.1 ]heptene

4.1. aH for some reactions calculated by MO methods 4.2. Calculated and experimental aH values for some isodesmic reactions 4.3. Substituent constants 4.4. Reaction constants 4.5. Classification of substituent groups 4.6. H o as a function of composition of aqueous sulfuric acid 4.7. Dielectric constants of some common solvents 4.8. Y values for some solvent systems 4.9. ET (30), an empirical measure of polarity, compared with dielectric

constant 4.10. Comparison of substituent contributions to phenol ionization in the gas

phase and solution 4.11. Acidities of simple alcohols in solution

5.1. Values of pKR+ for some carbocations 5.2. Hydride affinity of some carbocations 5.3. aH for ionization of chlorides over a wide structural range 5.4. Destabilization of 2-propyl cation by electron-withdrawing substituents 5.5. Nucleophiiic constants of various nucleophiles 5.6. Hardness and softness of some common ions and molecules 5.7. Solvent nucleophilicity (NTos) and ionization (YTos) parameters 5.8. Relative solvolysis rates of 1-phenylethyl esters and halides 5.9. Relative solvolysis rates of ethyl sulfonates and halides 5.10. Tosylate/bromide rate ratios for solvolysis of RX in 80% ethanol 5.11. Rate constants for nucleophilic substitution in primary alkyl substrates 5.12. Relative hydrolysis rates of 2-alkyl-2-adamantyl p-nitrobenzoates 5.13. a-Substituent effects 5.14. Stereochemical course of nucleophilic substitution reactions 5.15. Stereochemical course of deamination reactions in acetic acid

5.16. Product composition from deamination of stereoisomeric amines 5.17. Solvolysis rates of w-chloroalcohols 5.18. Relative solvolysis rates of some w-methoxyalkyl

p- bromobenzenesulfonates in acetic acid 5.19. Extent of aryl rearrangement in 2-phenylethyl tosylate solvolysis 5.20. Extent of solvolysis with aryl participation as a function of substituent and

solvent for 1-aryl-2-propyl tosylates

6.1. Rates of hydration of some alkenes in aqueous sulfuric acid 6.2. Stereochemistry of halogenation 6.3. Relative reactivity of alkenes toward halogenation 6.4. Product ratios for some E2 eliminations 6.5. Orientation in E2 elimination as a function of base strength 6.6. Orientation of elimination in the 2-butyl system under various E2

conditions 6.7. Extent of syn elimination as a function of the leaving group in the 5-decyl

system 6.8. Stereochemistry of E2 eliminations for some acyclic substrates

7.1. Values of H_ for some representative solvent-base syste~s 7.2. Acidities of some hydrocarbons 7.3. Equilibrium acidities of substituted methanes in dimethyl sulfoxide 7.4. Relative rates of base-catalyzed deuteriation of some ketones 7.5. Acidities of some cyano compounds 7.6. Acidities of some compounds with sulfur and phosphorus substituents 7.7. Relative rates of acid-catalyzed enolization for some ketones 7.8. Equilibrium constants for enolization of some carbonyl compounds

8.1. Hydration carbonyl compounds 8.2. Stereoselectivity in addition of organometallic reagents to some chiral

aldehydes and ketones 8.3. Rates of reduction of aldehydes and ketones by sodium borohydride 8.4. Relative reactivity of some ketones toward addition of nucleophiles

9.1. Hiickel's rule relationships for charged species 9.2. Energy values for reference bond types 9.3. Rates of Diels-Alder addition of linear polycyclic aromatic hydrocarbons

10.1. Energy changes for isodesmic proton transfer reactions of substituted benzenes

10.2. Percent meta nitration for some alkyl groups with electron-withdrawing substituents

10.3. Isomer proportions in the nitration of some substituted benzenes 10.4. Selectivity in some electrophilic aromatic substitution reactions 10.5. Values of p for some electrophilic aromatic substitution reactions

xxi LIST OF TABLES

XXll 10.6. 10.7.

LIST OF TABLES

10.8.

10.9. 10.10.

11.1 11.2.

12.1. 12.2. 12.3. 12.4. 12.5.

12.6. 12.7.

13.1.

Kinetic isotope effects in some electrophilic aromatic substitution reactions Relative reactivity and position selectivity for nitration of some aromatic compounds Partial rate factors for hydrogen exchange in some substituted aromatic compounds Toluene-benzene reactivity ratios in Friedel-Crafts alkylation reactions Substrate and position selectivity in Friedel-Crafts acylation reactions

Relative reactivity toward cyclopentadiene in the Diels-Alder reaction Relative reactivity of substituted butadienes in the Diels-Alder reaction

Oxidation and reduction potentials for some aromatic hydrocarbons Absolute rates of some free-radical reactions Regioselectivity of radical cyclization as a function of ring size Bond dissociation energies Thermochemical stabilization energies for some substituted radicals Relative rates of radical addition as a function of alkene substitution Relative reactivities of some aromatic hydrocarbons towared oxygen

General wavelength ranges for lowest-energy absorption band of some classes of photochemical substrates

List of Figures

1.1. Idealized view of u-bond formation by overlap of (a) an s and a p orbital and (b) two p orbitals

1.2. Cross section of angular dependence of orbitals 1.3. The 7T bond in ethylene 1.4. 7T-Bonding in acetylene 1.5. Bent bonds in cyclopropane 1.6. Charge distributions in strained cyclic hydrocarbons in comparison with

cyclohexane 1. 7 . Strain energies of some propellanes 1.8. Total energy as a function of distortion from planarity for methyl cation,

methyl radical, and methyl anion 1.9. Graphic description of combination of two Is orbitals to give two

molecular orbitals 1.10. Energy level diagram for HHe+ 1.11. Energy levels in the carbon monoxide molecule 1.12. Interaction of atomic orbitals of carbon and oxygen leading to molecular

orbitals of carbon monoxide 1.13. Representation of the molecular orbitals of carbon monoxide 1.14. Molecular orbital energy diagram for methane 1.15. Atomic orbitals of carbon relative to methane in a cubic frame of

reference 1.16. Atomic orbital combinations giving rise to bonding molecular orbitals for

methane 1.17. Qualitative molecular orbital diagram for methane 1.18. ESCA spectrum of methane 1.19. Ethylene molecular orbital energy levels 1.20. Representation of the molecular orbitals of ethylene

xxiii

xxiv

LIST OF FIGURES

1.21. Log scale plot of u-electron density in a plane bisecting the carbon atoms and perpendicular to the plane of the molecule

1.22. Log scale plot of 1T-electron density in a plane bisecting the carbon atoms and perpendicular to the plane of the molecule

1.23. Graphic representation of 1T-molecular orbitals of 1,3,5-hexatriene as combinations of 2p AOs

1.24. Energy level diagrams for cyclobutadiene and benzene 1.25. Energy level diagrams for cyclobutadiene and benzene, illustrating the

application of Frost's circle 1.26. Energy level diagrams for C3H3 and CsHs systems 1.27. Relative energy of the 1T and 1T* orbitals in ethylene and formaldehyde 1.28. PMO description of interaction of ethylene and formaldehyde with an

electrophile (E+) and a nucleophile (Nu-) 1.29. Orbital coefficients for the HOMO and LUMO of acrolein 1.30. MOs for ethylene and allyl cation 1.31. MO diagram showing mutual perturbation of MOs of butadiene and allyl

cation 1.32. Interactions between two hydrogen Is orbitals and carbon 2pz orbitals

stabilize the eclipsed conformation of propene 1.33. Interaction between CH3 - 1T and CH3 - 1T* orbitals and carbon 2pz

orbitals 1.34. Molecular orbitals of ethane revealing 1T character of 1Tz , 1Ty , 1T~, and 1T~

orbitals

2.1. UV absorption, ORO, and CD curves of ethyl methyl p-tolyl sulfonium tetraftuoroborate

2.2. CD spectra of (S)- and (R)-2-amino-l-phenyl-l-propanone hydrochloride 2.3. Stereoisomeric relationships in 2,3,4-trihydroxybutanal 2.4. Basis of kinetic resolution 2.5. Oepende~ce of enantiomeric excess on relative rate of reaction with a

chiral reagent in a kinetic resolution 2.6. NMR spectrum of I-phenylethylamine in presence of chiral shift reagent,

showing differential chemical shift of methine and methyl signals and indicating ratio of R- to S-enantiomers

2.7. Equivalent benzyl CH2 protons in I-benzyl-cis-2,6-dimethylpiperidine compared with nonequivalent protons in trans isomer

3.1. Potential energy as a function of torsion angle for ethane 3.2. Energy as a function of internuclear distance for nonbonded atoms 3.3. Potential energy diagram for rotation about C-2-C-3 bond of n-butane 3.4. Energy diagram for ring inversion of cyclohexane 3.5. Appearance of NMR spectra for system undergoing two-site exchange

(A~B)

3.6. NMR spectrum of cyclohexyl iodide at -80°C 3.7. Equivalent diamond-lattice conformations of cyclodecane (boat-chair

boat)

3.8. Approximate energy diagram for acetylation of cis- and trans-4-tbutylcyclohexanol

3.9. Approximate energy diagram for oxidation of cis- and trans-4-tbutylcyclohexanol

3.10. Approximate energy diagram for saponification of ethyl esters of cis- and trans-4-t-butylcyclohexanecarboxylic acid

3.11. Rates of ring closure for w-bromoalkanecarboxylates and w

bromoalkyloxyphenolates

4.1. Potential energy diagrams for single-step and two-step reactions 4.2. Correlation of acid dissociation constants of benzoic acids with rates of

alkaline hydrolsis of ethyl benzoates 4.3. Resonance, field, and inductive components of substituent effects in

substituted benzenes 4.4. Kinetic versus thermodynamic control 4.5. Some typical potential energy diagrams that illustrate the application of

Hammond's postulate 4.6. Potential energy diagram for electrophilic aromatic substitution 4.7. Transition state energies in bromination 4.8. Effect of conformation on product distribution 4.9. Differing zero-point energies of protium- and deuterium-substituted

molecules as the cause of primary kinetic isotope effects 4.10. Brl2lnsted relation for hydrolysis of methyl cyclohexenyl ether 4.11. Solvation changes during ionization of t-butyl chloride 4.12. Potential energy diagrams showing effect of preferential solvation of

transition state and ground state on the activation energy 4.13. Space-filling molecular model depicting a metal cation complexed by 18-

crown-6 4.14. Reactant and transition state solvation in the reaction of ethyl acetate with

hydroxide ion

5.1. Potential energy diagram for nucleophilic substitution by the ionization (SNl) mechanics

5.2. Potential energy diagram for nucleophilic substitution by the direct displacement (SN2) mechanism

5.3. MO description of the transition state for an SN2 displacement at carbon 5.4. Schematic relationship between reactants, intermediate species, and

products in substitution proceeding through ion pairs 5.5. Potential energy diagrams for substitution mechanisms 5.6. Relationship between stability and potential lifetime of carbocation

intermediate and mechanism for substitution 5.7. Crystal structures of bis(cyclopropyl)hydroxymethyl cation and 1-

cyclopropyl-1-phenylhydroxymethyl cation 5.8. Contrasting potential energy diagrams for stable and unstable bridged

norbornyl cation 5.9. Crystal structures of substituted norbornyl cations

xxv LIST OF

FIGURES

xxvi

LIST OF FIGURES

6.1. 6.2.

6.3. 6.4.

6.5.

6.6.

Crystal structure of bromonium ion from adamantylideneadamantane Enthalpy differences of starting alkenes and transition states in bromination Variable transition state theory of elimination reactions Three-dimensional (More O'Ferrall) diagrams depicting transition state locations for EI, Elcb, and E2 mechanisms Representation of changes in transition state character in the variable transition state E2 elimination reaction Product-determining step for EI elimination

7.1. Crystal structures of phenyllithium 7.2. Crystal structures of some lithium enolates of ketones

8.1. Representation of transition states for the first stage of acetal hydrolysis 8.2. Contour plot showing a favored concerted mechanism for the first step in

acetal hydrolysis, in which proton transfer is more complete in the transition state than C-O bond breaking

8.3. Three-dimensional potential energy diagram for addition of a proton and nucleophile to a carbonyl group

8.4. Ldgarithm of the first-order rate constants for the hydrolysis of substituted benzylidene-l,l-dimethylethylamines as a function of pH

8.5. pH-Rate profile for release of salicylic acid from benzaldehyde disalicyl acetal

8.6. pH-Rate profile for compound 3

9.1. HMO energies for conjugated ring systems of three to nine carbon atoms 9.2. X-ray crystal structures of 1,6-methanodeca-l,3,5,7,9-pentaene and 1,6-

methanodeca-l ,3,5,7 ,9-pentaene-2-carboxylic acid 9.3. Carbon framework from X-ray crystal structure of syn

tricyclo[ 8.4.1.13.8]hexadeca-l ,3,5,7,9,11,13-heptaene 9.4. X-ray crystal structures of tricyclo[8.4.1.1 4.9]hexadeca-2,4,6,8,10,12,14-

heptaene and anti-tricyclo[8.4.1.14.9]hexadeca-2,4,6,8, 1 0, 12, 14-heptaene-5-carboxylic acid

9.5. Structure of TMEDA complex of lithium bicyclo[3.2.1]octa-2,6-dienide 9.6. Crystal structure of 9,10-diphenylbicyclo[6.2.0]deca-l,3,5,7,9-pentaene 9.7. Hiickel molecular orbitals for phenalene

10.1 1T-Molecular .orbitals and energy levels for the pentadienyl cation 10.2. MO diagram for anisole by application of perturbation for a methoxyl

substituent 10.3. Orbital coefficients for HOMO and next highest 1T orbital for some

substituted benzenes 10.4. Total 1T-electron density for some substituted benzenes 10.5. Transition states for highly reactive and less reactive electrophiles 10.6. Various potential energy profiles for electrophilic aromatic substitution

11.1 Symmetry properties for the 7T system of a conjugated diene 11.2. Symmetry properties of hexatriene molecular orbitals 11.3. Symmetry properties of cyc10butene and butadiene orbitals 11.4. Correlation diagram for cyc10butene and butadiene orbitals (symmetry

forbidden disrotatory reaction) 11.5. Correlation diagram for cyc10butene and butadiene orbitals (symmetry

allowed conrotatory reaction) 11.6. Classification of sigmatropic hydrogen shifts with respect to basis set

orbitals 11.7. Classification of sigmatropic shifts of alkyl groups with respect to basis set

orbitals 11.8. Symmetry properties of ethylene, butadiene, and cyclohexene orbitals with

respect to cyc1oaddition 11.9. Correlation diagram for ethylene, butadiene, and cyc10hexene orbitals 11.10. Classification of cyc1oaddition reactions with respect to basis set orbitals 11.11. Frontier orbital interactions in Diels-Alder reactions 11.12. Coefficients and relative energies of dienophile and diene molecular

orbitals 11.13. Orbital coefficients for HOMO and LUMO 7T MOs of some common 1,3-

dipoles 11.14. Estimated energy of frontier 7T orbitals for some connon 1,3-dipoles 11.15. Concerted cyc1oaddition of a ketene and an olefin

12.1. Hyperfine splitting in EPR spectra 12.2. Some EPR spectra of small organic free radicals 12.3. NMR spectra recorded during thermal decomposition of dibenzoyl

peroxide 12.4.. PMO representation of p-orbital interactions with C=C, C=O, and OR

substituents 12.5. Frontier orbital interactions between different combinations of substituted

radicals and alkenes

13.1. Energy level diagram and summary of photochemical processes 13.2. Orbital correlation diagram for two ground state ethylenes and

cyc10butane 13.3. Orbital correlation diagram for one ground state alkene and one excited

state alkene 13.4. Correlation of energy states involved in the photochemical butadiene-to

cyc10butene conversion 13.5. Energy diagram showing potential energy curves for interconversion of

ground (So), first and second singlet (SI and S2), and first triplet (Tl )

excited states 13.6. Symmetry properties for [1,4]-sigmatropic shifts with inversion and

retention

XXVll

LIST OF FIGURES

xxviii

LIST OF FIGURES

13.7. Absorption spectra of a cis-trans isomer pair 13.8. Energy of excited states involved in cis-trans isomerization of stilbene 13.9. Energy diagram illustrating differential in energy deficit for

photosensitized isomerization of cis and trans isomers

List of Schemes

1.1. Dipole moments for some organic compounds

2.1. Chiral compounds of sulfur and phosphorus 2.2. Examples of chiral molecules lacking asymmetric atoms 2.3. Chiral and achiral disubstituted cycloalkanes 2.4. Resolution of 2-phenyl-3-methylbutanoic acid 2.5. Examples of kinetic resolutions 2.6. Examples of enzymatic resolutions 2.7. Stereoisomeric alkenes and related molecules with the double-bond

geometry named according to the sequence rule 2.8. Stereospecific reactions 2.9. Stereoselective reactions 2.10. Enantioselective transformations based on enzyme-catalyzed reactions

which differentiate between enantiomers or enantiotopic substituents

3.1. Equilibria in compounds that exhibit the anomeric effect 3.2. Effects of functional-group orientation on rates and equilibria 3.3. Bridgehead alkenes 3.4. Relative rates of ring closure as a function of ring size

4.1. Some representative rate laws 4.2. Some representative kinetic isotope effects 4.3. Relative ordering of hardness and softness 4.4. Effect of solvent polarity on reactions of various charge types

5.1. Representative nucleophilic substitution reactions 5.2. Rotational energy barriers for allyl cations 5.3. Protonation and ionization of organic substrates in superacid media

xxix

xxx

LIST OF SCHEMES

5.4. Competition between nucleophilicity and basicity 5.5. Other examples of nonclassical carbo cations

6.1. Some examples of J3-elimination reactions

7.1. Composition of ketone-enolate mixtures formed under kinetic and thermodynamic conditions

7.2. Alkylation of some organometallic reagents

8.1. Acetals and ketals that exhibit general acid catalysis in hydrolysis 8.2. Some addition-elimination reactions of aldehydes and ketones

9.1. Completely conjugated cyclic cations and anions 9.2. Stabilization energies of some conjugated hydrocarbons 9.3. Correlation between Ea for retro-Diels-Alder reaction and resonance

stabilization of aromatic products 9.4. Completely conjugated hydrocarbons incorporating exocyclic double

bonds 9.5. Heteroaromatic structures isoelectronic with benzene or naphthalene

10.1. Electrophilic species active in aromatic substitution 10.2. Generalized mechanism for electrophilic aromatic substitution

11.1. Examples of sigmatropic rearrangements 11.2. Generalized selection rules for sigmatropic processes 11.3. Regioselectivity of the Diels-Alder reaction 11.4. Some 1,3-dipoles

12.1. Stability of some free radicals 12.2. Stereochemistry of radical reactions at chiral carbon atoms 12.3. Radicals with capto-dative stabilization 12.4. Radical halogenations 12.5. Free-radical chain additions to alkenes 12.6. Free-radical rearrangements 12.7. Carbon alkylation via nitro alkane radical anions generated by electron

transfer 12.8. Aromatic substitution by the SRN 1 mechanism

13.1. Some examples of photochemical cycloaddition and electro cyclic reactions

part a: structure and mechanisms - springer978-1-4613-9795-3/1.pdf · 2.3. stereochemistry of...

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