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IntermedIate OrganIc chemIstry

IntermedIate OrganIc chemIstry

Third Edition

ann m. FabIrkIewIczDepartment of Chemistry Randolph College Lynchburg, Virginia

JOhn c. stOwellDepartment of Chemistry University of New Orleans New Orleans, Louisiana

Copyright 2016 by John Wiley & Sons, Inc. All rights reserved

Published by John Wiley & Sons, Inc., Hoboken, New JerseyPublished simultaneously in Canada

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Library of Congress CataloginginPublication Data:

Fabirkiewicz, Ann M., 1960 Intermediate organic chemistry / Ann M. Fabirkiewicz, Department of Chemistry, Randolph College, Lynchburg, Virginia, John C. Stowell, Department of Chemistry, University of New Orleans, New Orleans, Louisiana. Third edition. pages cm Includes bibliographical references and index. ISBN 978-1-118-30881-3 (cloth) ISBN (invalid) 978-1-118-66227-4 (pdf) ISBN 978-1-118-66220-5 (epub)1. Chemistry, OrganicTextbooks. I. Stowell, John C. (John Charles), 19381996 II. Title. QD251.2.S75 2016 547dc23 2015010086

Printed in the United States of America

10 9 8 7 6 5 4 3 2 1

1 2016

http://www.copyright.comhttp://www.wiley.com/go/permissionshttp://www.wiley.com

Contents

Preface to the third edition xi

Preface to the second edition xiii

Preface to the First edition xv

1 Reading nomenclature 1

1.1 Acyclic Polyfunctional Molecules, 21.2 Monocyclic Aliphatic Compounds, 31.3 Bridged Polycyclic Structures, 41.4 Fused Polycyclic Compounds, 61.5 Spiro Compounds, 101.6 Monocyclic Heterocyclic Compounds, 121.7 FusedRing Heterocyclic Compounds, 141.8 Bridged and Spiro Heterocyclic Compounds, 19Resources, 20Problems, 21References, 22

vi ContentS

2 Accessing Chemical Information 25

2.1 Databases, 252.2 Chemical Literature, 262.3 Synthetic Procedures, 292.4 Health and Safety Information, 30Problems, 32References, 33

3 stereochemistry 35

3.1 Representations, 353.2 Vocabulary, 373.3 Property Differences Among Stereoisomers, 403.4 Resolution of enantiomers, 443.5 enantioselective Synthesis, 473.6 Reactions at a Stereogenic Atom, 49

3.6.1 Racemization, 493.6.2 epimerization, 503.6.3 Inversion, 513.6.4 Retention, 513.6.5 transfer, 52

3.7 Relative and Absolute Configuration, 533.8 topism, 56Resources, 59Problems, 60References, 65

4 Mechanisms and Predictions 69

4.1 Reaction Coordinate Diagrams andMechanisms, 694.2 the Hammond Postulate, 714.3 Methods for Determining Mechanisms, 72

4.3.1 Identification of Products and Intermediates, 724.3.2 Isotope tracing, 734.3.3 Stereochemical Determination, 744.3.4 Concentration Dependence of Kinetics, 754.3.5 Isotope effects in Kinetics, 85

ContentS vii

4.3.6 temperature effects on Kinetics, 874.3.7 Substituent effects on Kinetics, 90

4.4 Representative Mechanisms, 954.4.1 Reactions in Basic Solution, 964.4.2 Reactions in Acidic Solution, 1004.4.3 FreeRadical Reactions, 1034.4.4 Molecular Rearrangements, 106

Resources, 108Problems, 109References, 120

5 electron Delocalization, Aromatic Character, andPericyclic Reactions 123

5.1 Molecular orbitals, 1245.2 Aromatic Character, 1305.3 Pericyclic Reactions, 135

5.3.1 Cycloaddition Reactions, 1375.3.2 electrocyclic Reactions, 1425.3.3 Sigmatropic Reactions, 147

Resources, 152Problems, 152References, 158

6 Functional Group transformations 163

6.1 Carboxylic Acids and Related Derivatives, 1646.1.1 Carboxylic Acids, 1646.1.2 Carboxylic esters, 1666.1.3 Carboxylic Amides, 1686.1.4 Carboxylic Acid Halides, 1686.1.5 Carboxylic Anhydrides, 1696.1.6 nitriles, 1696.1.7 ortho esters, 170

6.2 Aldehydes, Ketones, and Derivatives, 1716.2.1 Aldehydes, 1716.2.2 Ketones, 1746.2.3 Imines and enamines, 175

viii ContentS

6.2.4 Acetals, 1756.2.5 Vinyl ethers, 177

6.3 Alcohols, 1796.4 ethers, 1796.5 Alkyl Halides, 181

6.5.1 Alkyl Chlorides and Alkyl Bromides, 1826.5.2 Alkyl Iodides, 1846.5.3 Alkyl Fluorides, 184

6.6 Amines, 1856.7 Isocyanates, 1876.8 Alkenes, 1876.9 Reductive Removal of Functionality, 190Resources, 191Problems, 191References, 198

7 CarbonCarbon Bond Formation 205

7.1 CarbonCarbon Single Bond Formation, 2067.1.1 Reactions in Basic Solution, 2067.1.2 Reactions in Acidic Solution, 2147.1.3 organometallic Coupling Reactions, 217

7.2 CarbonCarbon DoubleBond Formation, 2187.3 Multibond Processes, 222Resources, 224Problems, 224References, 230

8 Planning Multistep syntheses 235

8.1 Retrosynthetic Analysis, 2358.2 Disconnection at a Functional Group

orBranch Point, 2368.3 Cooperation for Difunctionality, 2448.4 Ring Closure, 2508.5 Acetylide Alkylation and Addition, 2538.6 the DielsAlder Reaction, 2558.7 the Claisen Rearrangement, 2598.8 Synthetic Strategies, 2638.9 Final note, 265

ContentS ix

Resources, 266Problems, 266References, 271

9 Physical Influences onReactions 277

9.1 Unimolecular Reactions, 2789.2 Homogenous twoComponent Reactions, 2799.3 temperature effects, 2809.4 Pressure effects, 2819.5 Solvent effects, 2829.6 Biphasic Reactions, 283

9.6.1 Phase transfer Catalysis, 2839.6.2 Increasing Solubility, 2869.6.3 Increasing Surface Area, 2879.6.4 Ultrasound, 287

9.7 Reactions on Chemical Supports, 2889.8 Using Unfavorable equilibria, 2919.9 Green Chemistry, 293Resources, 294Problems, 294References, 295

10 survey of organic spectroscopy 299

10.1 electromagnetic Radiation, 29910.2 Ultraviolet Spectroscopy, 300

10.2.1 origin of the Signals, 30010.2.2 Interpretation, 30210.2.3 Visible Spectroscopy, 302

10.3 Infrared Spectroscopy, 30310.3.1 origin of the Signals, 30410.3.2 Interpretation, 304

10.4 Mass Spectrometry, 30510.4.1 origin of the Signals, 30610.4.2 Interpretation, 307

10.5 nMR Spectroscopy, 30910.5.1 origin of the Signals, 30910.5.2 Interpretation of Proton nMR Spectra, 311

x ContentS

10.6 Carbon nMR Spectra, 32310.6.1 General Characteristics, 32310.6.2 Interpretation of 13C nMR Spectra, 325

10.7 Correlation of 1H and 13C nMR Spectra, 327Resources, 329Problems, 329References, 333

Appendix A 337

Appendix B 341

Index 347

Preface to the third edition

When I read the first edition of Stowells Intermediate Organic Chemistry, I knew I had found an ideal text for a onesemester advanced organic chemistry course. The text was manageable in one semester, and the exten-sive references into the primary literature served as an introduction for students interested in pursuing organic chemistry in greater depth and made the text a useful reference beyond the scope of the course.

In this revision, I tried to stay true to the features that attracted me to the text initially, well described in Professor Stowells preface to the second edition. The organization of the book remains much the same. The chapter on mechanisms has been moved to early pages of the book, as has been the chapter on pericyclic reactions. My inclination is to teach mechanisms early as a foundation for the study of reactions, but all the chapters have been written with the intent that they can be introduced to the student in any order. As much as possible, open source materials are cited allowing students ready access to the original literature, but at the same time, the early work on a topic is found in older literature and that historical value is recognized. The second chapter has been completely rewritten to focus on internet accessible resources. The last chapter has also been completely rewritten to focus on a survey of organic spectroscopy.

I have tried to make this text as error free as possible, knowing the frustration of a missing or mistaken reference, or a bond misplaced in a

xii PrefAce To The ThIrd edITIon

chemical structure. I welcome input from readers of this text. Please contact me directly at afab@randolphcollege.edu.

I want to thank my husband Steve for his patience and support during the preparation of this manuscript. My son Adam is a source of support and insight. My mom is an inspiration. My colleague Abraham Yousef at Sweet Briar college was helpful in obtaining figures 10.6 and 10.14. Jonathan rose and the team at Wiley have been responsive to all my ques-tions and their assistance is invaluable. The support of my family and colleagues has made this work possible.

Lynchburg, Virginia Ann M. fabirkiewiczApril 2015

http://afab@randolphcollege.edu

Preface to the Second edition

consider the typical student who, having finished the twosemester introductory course in organic chemistry and then picking up an issue of the Journal of Organic Chemistry, finds the real world of the practicing chemist to be mostly out of reach, requiring a higher level of understanding. This text is intended to bridge that gap and equip a student to delve into new material.

There are two things to know while studying organic chemistry. one is the actual chemistry, that is, the behavior of compounds of carbon in various circumstances. The other is the edifice of theory, vocabulary, and sym-bolism that has been erected to organize the facts. In firstyear texts, there is an emphasis on the latter with little connection to the actual observables. Thus students are able to answer subtle questions about reactions without knowing quite how the information is obtained. chemistry is anchored in observations of specific cases, which can be obscured by the abstractions. for this reason, this text includes specific cases with more details and literature references to illustrate the general principles. Understanding these cases is an exercise to ensure the understanding of those general principles in a concrete way.

Many of the problems begin with raw data and require multistep thinking. Therefore, the student must solve a problem from the beginning rather than from a halffinished setup, and more thought and puzzling is necessary.

Title PageCopyright PageContentsPreface to the Third EditionPreface to the Second EditionPreface to the First EditionChapter 1 Reading Nomenclature1.1 ACYCLIC POLYFUNCTIONAL MOLECULES1.2 MONOCYCLIC ALIPHATIC COMPOUNDS1.3 BRIDGED POLYCYCLIC STRUCTURES1.4 FUSED POLYCYCLIC COMPOUNDS1.5 SPIRO COMPOUNDS1.6 MONOCYCLIC HETEROCYCLIC COMPOUNDS1.7 FUSED-RING HETEROCYCLIC COMPOUNDS1.8 BRIDGED AND SPIRO HETEROCYCLIC COMPOUNDSRESOURCESPROBLEMSREFERENCES

Chapter 2 Accessing Chemical Information2.1 DATABASES2.2 CHEMICAL LITERATURE2.3 SYNTHETIC PROCEDURES2.4 HEALTH AND SAFETY INFORMATIONPROBLEMSREFERENCES

Chapter 3 Stereochemistry3.1 REPRESENTATIONS3.2 VOCABULARY3.3 PROPERTY DIFFERENCES AMONG STEREOISOMERS3.4 RESOLUTION OF ENANTIOMERS3.5 ENANTIOSELECTIVE SYNTHESIS3.6 REACTIONS AT A STEREOGENIC ATOM3.6.1 Racemization3.6.2 Epimerization3.6.3 Inversion3.6.4 Retention3.6.5 Transfer

3.7 RELATIVE AND ABSOLUTE CONFIGURATION3.8 TOPISMRESOURCESPROBLEMSREFERENCES

Chapter 4 Mechanisms and Predictions4.1 REACTION COORDINATE DIAGRAMS ANDMECHANISMS4.2 THE HAMMOND POSTULATE4.3 METHODS FOR DETERMINING MECHANISMS4.3.1 Identification of Products and Intermediates4.3.2 Isotope Tracing4.3.3 Stereochemical Determination4.3.4 Concentration Dependence of Kinetics4.3.5 Isotope Effects in Kinetics4.3.6 Temperature Effects on Kinetics4.3.7 Substituent Effects on Kinetics

4.4 REPRESENTATIVE MECHANISMS4.4.1 Reactions in Basic Solution4.4.2 Reactions in Acidic Solution4.4.3 Free-Radical Reactions4.4.4 Molecular Rearrangements

RESOURCESPROBLEMSREFERENCES

Chapter 5 Electron Delocalization, Aromatic Character, andPericyclic Reactions5.1 MOLECULAR ORBITALS5.2 AROMATIC CHARACTER5.3 PERICYCLIC REACTIONS5.3.1 Cycloaddition Reactions5.3.2 Electrocyclic Reactions5.3.3 Sigmatropic Reactions

RESOURCESPROBLEMSREFERENCES

Chapter 6 Functional Group Transformations6.1 CARBOXYLIC ACIDS AND RELATED DERIVATIVES6.1.1 Carboxylic Acids6.1.2 Carboxylic Esters6.1.3 Carboxylic Amides6.1.4 Carboxylic Acid Halides6.1.5 Carboxylic Anhydrides6.1.6 Nitriles6.1.7 Ortho Esters

6.2 ALDEHYDES, KETONES, AND DERIVATIVES6.2.1 Aldehydes6.2.2 Ketones6.2.3 Imines and Enamines6.2.4 Acetals6.2.5 Vinyl Ethers

6.3 ALCOHOLS6.4 ETHERS6.5 ALKYL HALIDES6.5.1 Alkyl Chlorides and Alkyl Bromides6.5.2 Alkyl Iodides6.5.3 Alkyl Fluorides

6.6 AMINES6.7 ISOCYANATES6.8 ALKENES6.9 REDUCTIVE REMOVAL OF FUNCTIONALITYRESOURCESPROBLEMSREFERENCES

Chapter 7 CarbonCarbon Bond Formation7.1 CARBONCARBON SINGLE BOND FORMATION7.1.1 Reactions in Basic Solution7.1.2 Reactions in Acidic Solution7.1.3 Organometallic Coupling Reactions

7.2 CARBONCARBON DOUBLE-BOND FORMATION7.3 MULTIBOND PROCESSESRESOURCESPROBLEMSREFERENCES

Chapter 8 Planning Multistep Syntheses8.1 RETROSYNTHETIC ANALYSIS8.2 DISCONNECTION AT A FUNCTIONAL GROUP ORBRANCH POINT8.3 COOPERATION FOR DIFUNCTIONALITY8.4 RING CLOSURE8.5 ACETYLIDE ALKYLATION AND ADDITION8.6 THE DIELSALDER REACTION8.7 THE CLAISEN REARRANGEMENT8.8 SYNTHETIC STRATEGIES8.9 FINAL NOTERESOURCESPROBLEMSREFERENCES

Chapter 9 Physical Influences onReactions9.1 UNIMOLECULAR REACTIONS9.2 HOMOGENOUS TWO-COMPONENT REACTIONS9.3 TEMPERATURE EFFECTS9.4 PRESSURE EFFECTS9.5 SOLVENT EFFECTS9.6 BIPHASIC REACTIONS9.6.1 Phase Transfer Catalysis9.6.2 Increasing Solubility9.6.3 Increasing Surface Area9.6.4 Ultrasound

9.7 REACTIONS ON CHEMICAL SUPPORTS9.8 USING UNFAVORABLE EQUILIBRIA9.9 GREEN CHEMISTRYRESOURCESPROBLEMSREFERENCES

Chapter 10 Survey of Organic Spectroscopy10.1 ELECTROMAGNETIC RADIATION10.2 ULTRAVIOLET SPECTROSCOPY10.2.1 Origin of the Signals10.2.2 Interpretation10.2.3 Visible Spectroscopy

10.3 INFRARED SPECTROSCOPY10.3.1 Origin of the Signals10.3.2 Interpretation

10.4 MASS Spectrometry10.4.1 Origin of the Signals10.4.2 Interpretation

10.5 NMR SPECTROSCOPY10.5.1 Origin of the Signals10.5.2 Interpretation of Proton NMR Spectra

10.6 CARBON NMR SPECTRA10.6.1 General Characteristics10.6.2 Interpretation of 13C NMR Spectra

10.7 CORRELATION OF 1H AND 13C NMR SPECTRARESOURCESPROBLEMSREFERENCES

Appendix A Common Chemical AbbreviationsRESOURCES

Appendix B Common Protecting GroupsRESOURCES

IndexEULA