ORGANIC C H E M I S T RY NI N T H GL O B AL E DI T I O N E DI T I O N LEROY G WADE, JR WHITMAN COLLEGE C O N T R I B U T I N G AU T H O R : JAN WILLIAM SIMEK C A L I F O R N I A P O LY T E C H N I C S T AT E U N I V E R S I T Y Editor-in-Chief: Jeanne Zalesky Executive Editor: Terry Haugen Product Marketing Manager: Elizabeth Ellsworth Executive Field Marketing Manager: Chris Barker Director of Development: Jennifer Hart Development Editor: David Chelton Project Manager: Elisa Mandelbaum Program Manager: Lisa Pierce Editorial Assistant: Fran Falk Associate Content Producer: Lauren Layn Marketing Assistant: Megan Riley Team Lead, Project Management: David Zielonka Team Lead, Program Management: Kristen Flathman Assistant Acquisitions Editor, Global Edition: Murchana Borthakur Senior Project Editor, Global Edition: Amrita Naskar Manager, Media Production, Global Edition: Vikram Kumar Senior Manufacturing Controller, Production, Global Edition: Trudy Kimber Project Manager: GEX Publishing 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published by Pearson Education © 2017 All rights reserved No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without either the prior written permission of the publisher or a license permitting restricted copying in the United Kingdom issued by the Copyright Licensing Agency Ltd, Saffron House, 6–10 Kirby Street, London EC 1N 8TS All trademarks used herein are the property of their respective owners The use of any trademark in this text does not vest in the author or publisher any trademark ownership rights in such trademarks, nor does the use of such trademarks imply any affiliation with or endorsement of this book by such owners PEARSON, ALWAYS LEARNING, and MasteringCHEMISTRY, are exclusive trademarks in the U.S and/or other countries owned by Pearson Education, Inc or its affiliates Unless otherwise indicated herein, any third-party trademarks that may appear in this work are the property of their respective owners and any references to third-party trademarks, logos or other trade dress are for demonstrative or descriptive purposes only Such references are not intended to imply any sponsorship, endorsement, authorization, or promotion of Pearson’s products by the owners of such marks, or any relationship between the owner and Pearson Education, Inc or its affiliates, authors, licensees or distributors ISBN 10: 1-292-15110-2 ISBN 13: 978-1-292-15110-6 British Library Cataloguing-in-Publication Data A catalogue record for this book is available from the British Library 10 Typeset by GEX Publishing Services Printed and bound by Vivar in Malaysia To my students and colleagues at Whitman College About the Authors L G “Skip” Wade decided to become a chemistry major during his sophomore year at Rice University, while taking organic chemistry from Professor Ronald M Magid After receiving his B.A from Rice in 1969, Wade went on to Harvard University, where he did research with Professor James D White While at Harvard, he served as the Head Teaching Fellow for the organic laboratories and was strongly influenced by the teaching methods of two master educators, Professors Leonard K Nash and Frank H Westheimer After completing his Ph.D at Harvard in 1974, Dr Wade joined the chemistry faculty at Colorado State University Over the course of fifteen years at Colorado State, Dr Wade taught organic chemistry to thousands of students working toward careers in all areas of biology, chemistry, h uman medicine, veterinary medicine, and environmental studies He also authored research papers in organic synthesis and in chemical education, as well as eleven books reviewing current research in organic synthesis In 1989, Dr. Wade joined the chemistry faculty at Whitman College, where he continued to teach organic chemistry and pursue research interests in o rganic synthesis and forensic chemistry Dr Wade received the A E Lange Award for Distinguished Science Teaching at Whitman in 1993 Dr Wade’s interest in forensic science has led him to testify as an expert witness in court cases involving drugs and firearms, and he has worked as a police firearms instructor, drug consultant, and boating safety officer He also enjoys repairing and restoring old violins and bows, which he has done professionally for many years Jan Simek was born to humble, coal-mining parents who taught him to a ppreciate the importance of carbon at a very early age At age 14, he was inspired to pursue a career teaching chemistry by his high school c hemistry teacher, Joe Plaskas Under the guidance of Professor Kurt Kaufman at Kalamazoo College, Dr Simek began lab work in synthesis of natural products that turned into research in hop extracts for the Kalamazoo Spice Extraction Company After receiving a master’s degree from Stanford University, Dr Simek worked in the pharmaceutical industry, synthesizing compounds designed to control diabetes and atherosclerosis, and assisted in the isolation of anti-cancer antibiotics from natural sources Returning to Stanford University, Dr Simek completed his Ph.D with the legendary Professor Carl Djerassi, who developed the first synthesis of steroidal oral contraceptives Dr Simek’s 35-year teaching career was spent primarily at California Polytechnic State University, San Luis Obispo, where he received the university’s Distinguished Teaching Award Other teaching experiences include Albion College, the University of Colorado at Boulder, Kalamazoo College, and the University of California at Berkeley In addition to his pharmaceutical research, he has industrial experience investigating dyes, surfactants, and liquid crystals, and he continues to consult for the biotechnology industry Although his outside interests include free climbing in Yosemite, performing in a reggae band, and parasailing over the Pacific, as close as he gets to any of those is tending his backyard garden with his wife Judy Brief Contents Preface 25 Structure and Bonding 37 Acids and Bases; Functional Groups 91 Structure and Stereochemistry of Alkanes 143 The Study of Chemical Reactions 191 Stereochemistry 237 Alkyl Halides; Nucleophilic Substitution 283 Structure and Synthesis of Alkenes; Elimination 332 Reactions of Alkenes 395 Alkynes 464 10 Structure and Synthesis of Alcohols 496 11 Reactions of Alcohols 541 12 Infrared Spectroscopy and Mass Spectrometry 592 13 Nuclear Magnetic Resonance Spectroscopy 643 14 Ethers, Epoxides, and Thioethers 708 15 Conjugated Systems, Orbital Symmetry, and Ultraviolet Spectroscopy 752 16 Aromatic Compounds 800 17 Reactions of Aromatic Compounds 845 18 Ketones and Aldehydes 912 19 Amines 977 20 Carboxylic Acids 1038 21 Carboxylic Acid Derivatives 1079 22 Condensations and Alpha Substitutions of Carbonyl Compounds 1148 23 Carbohydrates and Nucleic Acids 1208 24 Amino Acids, Peptides, and Proteins 1258 25 Lipids 1301 26 Synthetic Polymers 1322 Appendices 1344 Brief Answers to Selected Problems 1368 Photo Credits 1374 Index 1375 4 Contents About the Authors Preface 25 STRUCTURE AND BONDING 37 1-1 1-2 1-3 1-4 1-5 O C S S N N OH luciferin OH luciferin Luciferin is the light-emitting compound found in many firefly (Lampyridae) species Luciferin reacts with atmospheric oxygen, under the control of an enzyme, to emit the yellow light that fireflies use to attract mates and prey The Origins of Organic Chemistry 37 Principles of Atomic Structure 39 Bond Formation: The Octet Rule 43 Lewis Structures 44 Multiple Bonding 45 Summary: Common Bonding Patterns (Uncharged) 45 1-6 Electronegativity and Bond Polarity 46 1-7 Formal Charges 47 Summary: Common Bonding Patterns in Organic Compounds and Ions 49 1-8 Ionic Structures 49 1-9 Resonance 50 PROBLEM-SOLVING STRATEGY: Drawing and Evaluating Resonance Forms 54 1-10 Structural Formulas 58 1-11 Molecular Formulas and Empirical Formulas 61 1-12 Wave Properties of Electrons in Orbitals 63 1-13 Molecular Orbitals 64 1-14 Pi Bonding 67 1-15 Hybridization and Molecular Shapes 68 1-16 Drawing Three-Dimensional Molecules 72 1-17 General Rules of Hybridization and Geometry 73 Summary: Hybridization and Geometry 73 1-18 Bond Rotation 78 1-19 Isomerism 80 Essential Terms 83 Study Problems 86 ACIDS AND BASES; FUNCTIONAL GROUPS 91 2-1 2-2 2-3 2-4 2-5 2-6 2-7 Polarity of Bonds and Molecules 92 Intermolecular Forces 96 Polarity Effects on Solubilities 100 Arrhenius Acids and Bases 103 Brønsted–Lowry Acids and Bases 104 Strengths of Acids and Bases 105 Equilibrium Positions of Acid–Base Reactions 109 PROBLEM-SOLVING STRATEGY: Predicting Acid–Base Equilibrium Positions 111 2-8 Solvent Effects on Acidity and Basicity 112 Summary: Acidity and Basicity Limitations in Common Solvents 114 5 6 Contents 2-9 Effects of Size and Electronegativity on Acidity 114 2-10 Inductive Effects on Acidity 116 2-11 Hybridization Effects on Acidity 117 2-12 Resonance Effects on Acidity and Basicity 119 2-13 Lewis Acids and Bases 122 2-14 The Curved-Arrow Formalism 124 2-15 Hydrocarbons 126 2-16 Functional Groups with Oxygen 129 2-17 Functional Groups with Nitrogen 132 Essential Terms 134 Study Problems 137 STRUCTURE AND STEREOCHEMISTRY OF ALKANES 143 3-1 Classification of Hydrocarbons (Review) 144 3-2 Molecular Formulas of Alkanes 144 3-3 Nomenclature of Alkanes 146 Summary: Rules for Naming Alkanes 151 3-4 Physical Properties of Alkanes 153 3-5 Uses and Sources of Alkanes 154 3-6 Reactions of Alkanes 157 3-7 Structure and Conformations of Alkanes 158 3-8 Conformations of Butane 162 3-9 Conformations of Higher Alkanes 165 3-10 Cycloalkanes 165 3-11 Cis-trans Isomerism in Cycloalkanes 167 3-12 Stabilities of Cycloalkanes; Ring Strain 168 3-13 Cyclohexane Conformations 172 PROBLEM-SOLVING STRATEGY: Drawing Chair Conformations 174 3-14 Conformations of Monosubstituted Cyclohexanes 176 3-15 Conformations of Disubstituted Cyclohexanes 179 PROBLEM-SOLVING STRATEGY: Recognizing Cis and Trans Isomers 179 3-16 Bicyclic Molecules 182 Essential Terms 184 Study Problems 188 THE STUDY OF CHEMICAL REACTIONS 4-1 4-2 4-3 4-4 4-5 4-6 4-7 4-8 191 Introduction 191 Chlorination of Methane 192 The Free-Radical Chain Reaction 193 Equilibrium Constants and Free Energy 197 Enthalpy and Entropy 199 Bond-Dissociation Enthalpies 201 Enthalpy Changes in Chlorination 202 Kinetics and the Rate Equation 205 Contents 7 4-9 Activation Energy and the Temperature Dependence of Rates 207 4-10 Transition States 208 4-11 Rates of Multistep Reactions 210 4-12 Temperature Dependence of Halogenation 211 4-13 Selectivity in Halogenation 212 4-14 Hammond’s Postulate 218 PROBLEM-SOLVING STRATEGY: Proposing Reaction Mechanisms 219 4-15 Radical Inhibitors 222 4-16 Reactive Intermediates 223 Summary: Reactive Intermediates 230 Essential Terms 230 Study Problems 233 STEREOCHEMISTRY 237 5-1 Introduction 237 5-2 Chirality 238 5-3 (R) and (S) Nomenclature of Asymmetric Carbon Atoms 244 5-4 Optical Activity 249 5-5 Biological Discrimination of Enantiomers 254 5-6 Racemic Mixtures 255 5-7 Enantiomeric Excess and Optical Purity 256 5-8 Chirality of Conformationally Mobile Systems 257 5-9 Chiral Compounds Without Asymmetric Atoms 260 5-10 Fischer Projections 262 Summary: Fischer Projections and Their Use 266 5-11 Diastereomers 266 Summary: Types of Isomers 268 5-12 Stereochemistry of Molecules with Two or More Asymmetric Carbons 269 5-13 Meso Compounds 269 5-14 Absolute and Relative Configuration 271 5-15 Physical Properties of Diastereomers 273 5-16 Resolution of Enantiomers 274 Essential Terms 277 Study Problems 280 ALKYL HALIDES; NUCLEOPHILIC SUBSTITUTION 283 6-1 Introduction 283 6-2 Nomenclature of Alkyl Halides 284 H3C O Cl 6-3 Common Br Uses of Alkyl Halides 286 H3C 6-4 Structure CH3 of Alkyl Halides 288 kumepaloxane 6-5 Physical Properties of Alkyl Halides 289 6-6 Preparation of Alkyl Halides 291 cymbal bubble snail Haminoea cymbalum Summary: Methods for Preparing Alkyl Halides 295 6-7 Reactions of Alkyl Halides: Substitution and Elimination 296 8 Contents 6-8 Bimolecular Nucleophilic Substitution: The SN2 Reaction 297 6-9 Generality of the SN2 Reaction 299 Summary: SN2 Reactions of Alkyl Halides 300 6-10 Factors Affecting SN2 Reactions: Strength of the Nucleophile 301 Summary: Trends in Nucleophilicity 302 6-11 Reactivity of the Substrate in SN2 Reactions 305 6-12 Stereochemistry of the SN2 Reaction 309 6-13 Unimolecular Nucleophilic Substitution: The SN1 Reaction 311 6-14 Stereochemistry of the SN1 Reaction 315 6-15 Rearrangements in SN1 Reactions 317 6-16 Comparison of SN1 and SN2 Reactions 320 Summary: Nucleophilic Substitutions 322 Summary: Reactions of Alkyl Halides 323 Essential Terms 324 Study Problems 327 STRUCTURE AND SYNTHESIS OF ALKENES; ELIMINATION 7-1 7-2 7-3 7-4 7-5 squalene 332 Introduction 332 The Orbital Description of the Alkene Double Bond 333 Elements of Unsaturation 335 Nomenclature of Alkenes 337 Nomenclature of Cis-Trans Isomers 339 Summary: Rules for Naming Alkenes 341 7-6 Commercial Importance of Alkenes 342 7-7 Physical Properties of Alkenes 344 7-8 Stability of Alkenes 346 7-9 Formation of Alkenes by Dehydrohalogenation of Alkyl Halides 354 7-10 Unimolecular Elimination: The E1 Reaction 355 Summary: Carbocation Reactions 359 7-11 Positional Orientation of Elimination: Zaitsev’s Rule 360 7-12 Bimolecular Elimination: The E2 Reaction 362 7-13 Bulky Bases in E2 Eliminations; Hofmann Orientation 364 7-14 Stereochemistry of the E2 Reaction 365 7-15 E2 Reactions in Cyclohexane Systems 368 7-16 Comparison of E1 and E2 Elimination Mechanisms 370 Summary: Elimination Reactions 371 7-17 Competition Between Substitutions and Eliminations 372 Summary: Substitution and Elimination Reactions of Alkyl Halides 374 PROBLEM-SOLVING STRATEGY: Predicting Substitutions and Eliminations 376 7-18 Alkene Synthesis by Dehydration of Alcohols 377 7-19 Alkene Synthesis by High-Temperature Industrial Methods 380 PROBLEM-SOLVING STRATEGY: Proposing Reaction Mechanisms 382 Summary: Methods for Synthesis of Alkenes 385 Essential Terms 386 Study Problems 389 Contents 9 REACTIONS OF ALKENES 395 8-1 Reactivity of the Carbon–Carbon Double Bond 395 8-2 Electrophilic Addition to Alkenes 396 8-3 Addition of Hydrogen Halides to Alkenes 398 8-4 Addition of Water: Hydration of Alkenes 406 8-5 Hydration by Oxymercuration–Demercuration 408 8-6 Alkoxymercuration–Demercuration 411 8-7 Hydroboration of Alkenes 412 8-8 Addition of Halogens to Alkenes 418 8-9 Formation of Halohydrins 421 8-10 Catalytic Hydrogenation of Alkenes 425 8-11 Addition of Carbenes to Alkenes 427 8-12 Epoxidation of Alkenes 429 8-13 Acid-Catalyzed Opening of Epoxides 431 8-14 Syn Dihydroxylation of Alkenes 434 8-15 Oxidative Cleavage of Alkenes 436 8-16 Polymerization of Alkenes 439 8-17 Olefin Metathesis 443 PROBLEM-SOLVING STRATEGY: Organic Synthesis 446 Summary: Reactions of Alkenes 448 Summary: Electrophilic Additions to Alkenes 451 Summary: Oxidation and Cyclopropanation Reactions of Alkenes 452 Essential Terms 453 Study Problems 457 ALKYNES 464 9-1 9-2 9-3 9-4 9-5 9-6 9-7 9-8 Introduction 464 Nomenclature of Alkynes 465 Physical Properties of Alkynes 467 Commercial Importance of Alkynes 467 Electronic Structure of Alkynes 469 Acidity of Alkynes; Formation of Acetylide Ions 470 Synthesis of Alkynes from Acetylides 472 Synthesis of Alkynes by Elimination Reactions 475 Summary: Syntheses of Alkynes 477 9-9 Addition Reactions of Alkynes 477 9-10 Oxidation of Alkynes 486 PROBLEM-SOLVING STRATEGY: Multistep Synthesis 488 Summary: Reactions of Alkynes 490 Summary: Reactions of Terminal Alkynes 491 Essential Terms 492 Study Problems 493 ... through their first mechanisms with greater clarity and with more opportunities to test and apply their understanding without getting overwhelmed by organic chemistry New problem-solving strategy... Chapter -by- Chapter Changes Global Changes Every chapter begins with a new chapter-opening photograph showing an interesting, real-world application of the material in that chapter New Problem-Solving... memorize PV = nRT, and I was good to go When I tried the same approach in organic, I got a D We learn by making mistakes, and I learned a lot in organic chemistry In writing this book, I’ve tried