Leroy G. Wade-Organic Chemistry-Prentice Hall (2012) (1).pdf

If you purchased this book within the United States or Canada you should be aware that it has been imported without the approval of the Publisher or the Author. Editor in Chief: Adam Jaworski Senior Technical Art Specialist: Connie Long Executive Editor: Jeanne Z...

If you purchased this book within the United States or Canada you should be aware that it has been imported without the approval of the Publisher or the Author. Editor in Chief: Adam Jaworski Senior Technical Art Specialist: Connie Long Executive Editor: Jeanne Zalesky Illustrator: Precision Graphics Senior Marketing Manager: Jonathan Cottrell Photo Manager: Maya Melenchuk Senior Project Editor: Jennifer Hart Photo Researcher: Eric Schrader VP/Executive Director, Development: Carol Trueheart Text Research Manager: Beth Wollar Development Editor: John Murdzek Text Researchers: Melissa Flamson and Assistant Editor: Coleen McDonald Natalie Giboney Turner Editorial Assistant: Lisa Tarabokjia Design Manager: Mark Ong Senior Media Producer: Angela Bernhardt Interior Design: Gary Hespenheide Marketing Assistant: Nicola Houston Cover Design: Jodi Notowitz Managing Editor, Chemistry and Geosciences: Operations Specialist: Jeff Sargent Gina M. Cheselka Spectra: ©Sigma-Aldrich Co. Senior Project Manager, Production: Shari Toron Cover Photo Credit: PhotoDisc Compositor: GEX Publishing Services Credits and acknowledgments borrowed from other sources and reproduced, with permission, in this textbook appear on the appropriate page within the text. Copyright © 2013, 2010, 2006, 2003, 1999, 1995, 1991, 1987 Pearson Education, Inc. All rights reserved. Manufactured in the United States of America. This publication is protected by Copyright, and permission should be obtained from the publisher prior to any prohibited reproduction, storage in a retrieval system, or transmission in any form or by any means, electronic, mechanical, photocopying, recording, or likewise. To obtain permission(s) to use material from this work, please submit a written request to Pearson Education, Inc., Permissions Department, 1900 E. Lake Ave., Glenview, IL 60025. For information regarding permissions, call (847) 486-2635. 1 2 3 4 5 6 7 8 9 10—CRK—15 14 13 12 11 ISBN-10: 0-321-81139-9; ISBN-13: 978-0-321-81139-4  ORGANIC CHEMISTRY EIGHTH EDITION L. G. WA D E , J R. WHITMAN C OLLEGE Boston Columbus Indianapolis New York San Francisco Upper Saddle River Amsterdam Cape Town Dubai London Madrid Milan Munich Paris Montréal Toronto Delhi Mexico City São Paulo Sydney Hong Kong Seoul Singapore Taipei Tokyo Editor in Chief: Adam Jaworski Senior Technical Art Specialist: Connie Long Executive Editor: Jeanne Zalesky Illustrator: Precision Graphics Senior Marketing Manager: Jonathan Cottrell Photo Manager: Maya Melenchuk Senior Project Editor: Jennifer Hart Photo Researcher: Eric Schrader VP/Executive Director, Development: Carol Trueheart Text Research Manager: Beth Wollar Development Editor: John Murdzek Text Researchers: Melissa Flamson and Assistant Editor: Coleen McDonald Natalie Giboney Turner Editorial Assistant: Lisa Tarabokjia Design Manager: Mark Ong Senior Media Producer: Angela Bernhardt Interior and Cover Design: Gary Hespenheide Marketing Assistant: Nicola Houston Operations Specialist: Jeff Sargent Managing Editor, Chemistry and Geosciences: Cover Photo Credit: Don Paulson Photography/ Gina M. Cheselka Purestock/Alamy Senior Project Manager, Production: Shari Toron Spectra: ©Sigma-Aldrich Co. Compositor: GEX Publishing Services Credits and acknowledgments borrowed from other sources and reproduced, with permission, in this textbook appear on the appropriate page within the text. Copyright © 2013, 2010, 2006, 2003, 1999, 1995, 1991, 1987 Pearson Education, Inc. All rights reserved. Manufactured in the United States of America. This publication is protected by Copyright, and permission should be obtained from the publisher prior to any prohibited reproduction, storage in a retrieval system, or transmission in any form or by any means, electronic, mechanical, photocopying, recording, or likewise. To obtain permission(s) to use material from this work, please submit a written request to Pearson Education, Inc., Permissions Department, 1900 E. Lake Ave., Glenview, IL 60025. For information regarding permissions, call (847) 486-2635. Library of Congress Cataloging-in-Publication Data Wade, L. G., Organic chemistry / L.G. Wade, Jr. -- 8th ed. p. cm. Includes index. ISBN 978-0-321-76841-4 (0-321-76841-8) 1. Chemistry, Organic--Textbooks. I. Title. QD251.3.W33 2013 547--dc23 2011041255 1 2 3 4 5 6 7 8 9 10—CRK—15 14 13 12 11 www.pearsonhighered.com ISBN-10: 0-321-76841-8; ISBN-13: 978-0-321-76841-4 To my students and colleagues at Whitman College About the Author 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, human 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. Since 1989, Dr. Wade has been a chemistry professor at Whitman College, where he teaches organic chemistry and pursues research interests in organic synthe- sis 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. iii Brief Contents Preface xxv 1 Introduction and Review 1 2 Structure and Properties of Organic Molecules 42 3 Structure and Stereochemistry of Alkanes 87 4 The Study of Chemical Reactions 132 5 Stereochemistry 174 6 Alkyl Halides: Nucleophilic Substitution and Elimination 218 7 Structure and Synthesis of Alkenes 285 8 Reactions of Alkenes 328 9 Alkynes 392 10 Structure and Synthesis of Alcohols 425 11 Reactions of Alcohols 467 12 Infrared Spectroscopy and Mass Spectrometry 513 13 Nuclear Magnetic Resonance Spectroscopy 563 14 Ethers, Epoxides, and Thioethers 625 15 Conjugated Systems, Orbital Symmetry, and Ultraviolet Spectroscopy 667 16 Aromatic Compounds 713 17 Reactions of Aromatic Compounds 756 18 Ketones and Aldehydes 816 19 Amines 879 20 Carboxylic Acids 939 21 Carboxylic Acid Derivatives 981 22 Condensations and Alpha Substitutions of Carbonyl Compounds 1045 23 Carbohydrates and Nucleic Acids 1101 24 Amino Acids, Peptides, and Proteins 1155 25 Lipids 1201 26 Synthetic Polymers 1222 Appendices 1243 Answers A1 Photo Credits PC1 Index I1 iv Contents About the Author iii Preface xxv 1 INTRODUCTION AND REVIEW 1 1-1 The Origins of Organic Chemistry 1 1-2 Principles of Atomic Structure 3 1-3 Bond Formation: The Octet Rule 6 1-4 Lewis Structures 7 1-5 Multiple Bonding 8 Summary: Common Bonding Patterns (Uncharged) 9 1-6 Electronegativity and Bond Polarity 10 1-7 Formal Charges 11 1-8 Ionic Structures 13 Summary: Common Bonding Patterns in Organic Compounds and Ions 13 1-9 Resonance 14 1-10 Structural Formulas 18 1-11 Molecular Formulas and Empirical Formulas 21 1-12 Arrhenius Acids and Bases 22 1-13 Brønsted–Lowry Acids and Bases 23 1-14 Lewis Acids and Bases 31 Essential Terms 34 Study Problems 36 STRUCTURE AND PROPERTIES 2 OF ORGANIC MOLECULES 42 2-1 Wave Properties of Electrons in Orbitals 42 2-2 Molecular Orbitals 44 2-3 Pi Bonding 47 2-4 Hybridization and Molecular Shapes 48 2-5 Drawing Three-Dimensional Molecules 52 2-6 General Rules of Hybridization and Geometry 53 2-7 Bond Rotation 58 2-8 Isomerism 60 2-9 Polarity of Bonds and Molecules 62 2-10 Intermolecular Forces 66 2-11 Polarity Effects on Solubilities 70 2-12 Hydrocarbons 72 2-13 Organic Compounds Containing Oxygen 76 2-14 Organic Compounds Containing Nitrogen 78 Essential Terms 81 Study Problems 83 v vi Contents STRUCTURE AND STEREOCHEMISTRY 3 OF ALKANES 87 3-1 Classification of Hydrocarbons (Review) 87 3-2 Molecular Formulas of Alkanes 88 3-3 Nomenclature of Alkanes 89 Summary: Rules for Naming Alkanes 94 3-4 Physical Properties of Alkanes 95 3-5 Uses and Sources of Alkanes 97 3-6 Reactions of Alkanes 99 3-7 Structure and Conformations of Alkanes 100 3-8 Conformations of Butane 104 3-9 Conformations of Higher Alkanes 106 3-10 Cycloalkanes 107 3-11 Cis-trans Isomerism in Cycloalkanes 109 3-12 Stabilities of Cycloalkanes; Ring Strain 109 3-13 Cyclohexane Conformations 113 Problem-Solving Strategy: Drawing Chair Conformations 116 3-14 Conformations of Monosubstituted Cyclohexanes 117 3-15 Conformations of Disubstituted Cyclohexanes 120 Problem-Solving Strategy: Recognizing Cis and Trans Isomers 122 3-16 Bicyclic Molecules 123 Essential Terms 125 Study Problems 129 4 THE STUDY OF CHEMICAL REACTIONS 132 4-1 Introduction 132 4-2 Chlorination of Methane 132 4-3 The Free-Radical Chain Reaction 134 Key Mechanism 4-1: Free-Radical Halogenation 136 4-4 Equilibrium Constants and Free Energy 138 4-5 Enthalpy and Entropy 140 4-6 Bond-Dissociation Enthalpies 142 4-7 Enthalpy Changes in Chlorination 143 4-8 Kinetics and the Rate Equation 145 4-9 Activation Energy and the Temperature Dependence of Rates 147 4-10 Transition States 148 4-11 Rates of Multistep Reactions 149 4-12 Temperature Dependence of Halogenation 150 4-13 Selectivity in Halogenation 151 4-14 The Hammond Postulate 157 4-15 Radical Inhibitors 161 4-16 Reactive Intermediates 162 Summary: Reactive Intermediates 168 Essential Terms 168 Study Problems 170  Contents vii 5 STEREOCHEMISTRY 174 5-1 Introduction 174 5-2 Chirality 175 5-3 (R) and (S) Nomenclature of Asymmetric Carbon Atoms 181 5-4 Optical Activity 185 5-5 Biological Discrimination of Enantiomers 189 5-6 Racemic Mixtures 191 5-7 Enantiomeric Excess and Optical Purity 192 5-8 Chirality of Conformationally Mobile Systems 193 5-9 Chiral Compounds without Asymmetric Atoms 195 5-10 Fischer Projections 197 5-11 Summary: Fischer Projections and Their Use 201 Diastereomers 201 Summary: Types of Isomers 203 5-12 Stereochemistry of Molecules with Two or More Asymmetric Carbons 204 5-13 Meso Compounds 205 5-14 Absolute and Relative Configuration 207 5-15 Physical Properties of Diastereomers 208 5-16 Resolution of Enantiomers 209 Essential Terms 213 Study Problems 215 ALKYL HALIDES: NUCLEOPHILIC 6 SUBSTITUTION AND ELIMINATION 218 6-1 Introduction 218 6-2 Nomenclature of Alkyl Halides 219 6-3 Common Uses of Alkyl Halides 221 6-4 Structure of Alkyl Halides 223 6-5 Physical Properties of Alkyl Halides 224 6-6 Preparation of Alkyl Halides 226 Mechanism 6-1: Allylic Bromination 228 Summary: Methods for Preparing Alkyl Halides 229 6-7 Reactions of Alkyl Halides: Substitution and Elimination 231 6-8 Second-Order Nucleophilic Substitution: The SN2 Reaction 232 Key Mechanism 6-2: The SN2 Reaction 233 6-9 Generality of the SN2 Reaction 234 Summary: SN2 Reactions of Alkyl Halides 234 6-10 Factors Affecting SN2 Reactions: Strength of the Nucleophile 236 Summary: Trends in Nucleophilicity 237 6-11 Reactivity of the Substrate in SN2 Reactions 240 6-12 Stereochemistry of the SN2 Reaction 244 Mechanism 6-3: Inversion of Configuration in the SN2 Reaction 244 6-13 First-Order Nucleophilic Substitution: The SN1 Reaction 246 Key Mechanism 6-4:The SN1 Reaction 247 6-14 Stereochemistry of the SN1 Reaction 250 6-15 Rearrangements in the SN1 Reactions 252 Mechanism 6-5: Racemization in the SN1 Reaction 252 viii Contents Mechanism 6-6: Hydride Shift in an SN1 Reaction 253 Mechanism 6-7: Methyl Shift in an SN1 Reaction 254 6-16 Comparison of SN1 and SN2 Reactions 255 Summary: Nucleophilic Substitutions 257 6-17 First-Order Elimination: The E1 Reaction 258 Key Mechanism 6-8:The E1 Reaction 258 Mechanism 6-9: Rearrangement in an E1 Reaction 261 Summary: Carbocation Reactions 262 6-18 Positional Orientation of Elimination: Zaitsev’s Rule 263 6-19 Second-Order Elimination: The E2 Reaction 265 Key Mechanism 6-10:The E2 Reaction 266 6-20 Stereochemistry of the E2 Reaction 267 6-21 Comparison of E1 and E2 Elimination Mechanisms 269 Problem-Solving Strategy: Predicting Substitutions and Eliminations 270 Summary: Elimination Reactions 270 Summary: Reactions of Alkyl Halides 273 Essential Terms 276 Study Problems 279 7 STRUCTURE AND SYNTHESIS OF ALKENES 285 7-1 Introduction 285 7-2 The Orbital Description of the Alkene Double Bond 286 7-3 Elements of Unsaturation 287 7-4 Nomenclature of Alkenes 289 7-5 Nomenclature of Cis-Trans Isomers 291 Summary: Rules for Naming Alkenes 293 7-6 Commercial Importance of Alkenes 294 7-7 Stability of Alkenes 296 7-8 Physical Properties of Alkenes 302 7-9 Alkene Synthesis by Elimination of Alkyl Halides 304 Mechanism 7-1: Dehydrohalogenation by the E2 Mechanism 304 Mechanism 7-2: Stereochemistry of the E2 Reaction 306 Mechanism 7-3: E2 Debromination of a Vicinal Dibromide 310 7-10 Alkene Synthesis by Dehydration of Alcohols 312 Key Mechanism 7-4: Acid-Catalyzed Dehydration of an Alcohol 313 7-11 Alkene Synthesis by High-Temperature Industrial Methods 315 Problem-Solving Strategy: Proposing Reaction Mechanisms 316 Summary: Methods for Synthesis of Alkenes 320 Essential Terms 322 Study Problems 323 8 REACTIONS OF ALKENES 328 8-1 Reactivity of the Carbon–Carbon Double Bond 328 8-2 Electrophilic Addition to Alkenes 329 Key Mechanism 8-1: Electrophilic Addition to Alkenes 330  Contents ix 8-3 Addition of Hydrogen Halides to Alkenes 331 Mechanism 8-2: Ionic Addition of HX to an Alkene 332 Mechanism 8-3: Free-Radical Addition of HBr to Alkenes 334 8-4 Addition of Water: Hydration of Alkenes 337 Mechanism 8-4: Acid-Catalyzed Hydration of an Alkene 338 8-5 Hydration by Oxymercuration–Demercuration 340 Mechanism 8-5: Oxymercuration of an Alkene 340 8-6 Alkoxymercuration–Demercuration 342 8-7 Hydroboration of Alkenes 343 Mechanism 8-6: Hydroboration of an Alkene 345 8-8 Addition of Halogens to Alkenes 349 Mechanism 8-7: Addition of Halogens to Alkenes 350 8-9 Formation of Halohydrins 352 Mechanism 8-8: Formation of Halohydrins 352 8-10 Catalytic Hydrogenation of Alkenes 355 8-11 Addition of Carbenes to Alkenes 358 8-12 Epoxidation of Alkenes 360 Mechanism 8-9: Epoxidation of Alkenes 360 8-13 Epoxidation of Alkenes 361 Mechanism 8-10: Acid-Catalyzed Opening of Epoxides 362 8-14 Syn Dihydroxylation of Alkenes 364 8-15 Oxidative Cleavage of Alkenes 366 8-16 Polymerization of Alkenes 369 8-17 Olefin Metathesis 373 Mechanism 8-11: Olefin Metathesis 376 Problem-Solving Strategy: Organic Synthesis 376 Summary: Reactions of Alkenes 378 Essential Terms 383 Study Problems 386 9 ALKYNES 392 9-1 Introduction 392 9-2 Nomenclature of Alkynes 393 9-3 Physical Properties of Alkynes 394 9-4 Commercial Importance of Alkynes 395 9-5 Electronic Structure of Alkynes 396 9-6 Acidity of Alkynes; Formation of Acetylide Ions 397 9-7 Synthesis of Alkynes from Acetylides 399 9-8 Synthesis of Alkynes by Elimination Reactions 403 Summary: Syntheses of Alkynes 404 9-9 Addition Reactions of Alkynes 405 Mechanism 9-1: Metal–Ammonia Reduction of an Alkyne 407 Mechanism 9-2: Acid-Catalyzed Keto–Enol Tautomerism 411 Mechanism 9-3: Base-Catalyzed Keto–Enol Tautomerism 413 9-10 Oxidation of Alkynes 414 Problem-Solving Strategy: Multistep Synthesis 416 Summary: Reactions of Alkynes 418 Essential Terms 421 Study Problems 422 x Contents STRUCTURE AND SYNTHESIS 10 OF ALCOHOLS 425 10-1 Introduction 425 10-2 Structure and Classification of Alcohols 425 10-3 Nomenclature of Alcohols and Phenols 427 10-4 Physical Properties of Alcohols 430 10-5 Commercially Important Alcohols 433 10-6 Acidity of Alcohols and Phenols 435 10-7 Synthesis of Alcohols: Introduction and Review 438 Summary: Previous Alcohol Syntheses 438 10-8 Organometallic Reagents for Alcohol Synthesis 440 10-9 Addition of Organometallic Reagents to Carbonyl Compounds 443 Key Mechanism 10-1: Grignard Reactions 443 Summary: Grignard Reactions 450 10-10 Side Reactions of Organometallic Reagents: Reduction of Alkyl Halides 451 10-11 Reduction of the Carbonyl Group: Synthesis of 1° and 2° Alcohols 453 Mechanism 10-2: Hydride Reduction of a Carbonyl Group 454 Summary: Reactions of LiAIH4 and NaBH4 455 Summary: Alcohol Syntheses by Nucleophilic Additions to Carbonyl Groups 457 10-12 Thiols (Mercaptans) 458 Essential Terms 461 Study Problems 462 11 REACTIONS OF ALCOHOLS 467 11-1 Oxidation States of Alcohols and Related Functional Groups 467 11-2 Oxidation of Alcohols 469 11-3 Additional Methods for Oxidizing Alcohols 472 11-4 Biological Oxidation of Alcohols 474 11-5 Alcohols as Nucleophiles and Electrophiles; Formation of Tosylates 476 Summary: SN2 Reactions Of Tosylate Esters 478 11-6 Reduction of Alcohols 478 11-7 Reactions of Alcohols with Hydrohalic Acids 479 Mechanism 11-1: Reaction of a Tertiary Alcohol with HBr (SN1) 480 Mechanism 11-2: Reaction of a Primary Alcohol with HBr (SN2) 480 11-8 Reactions of Alcohols with Phosphorus Halides 484 Reactions of Alcohols with Thionyl Chloride 485 11-9 Mechanism 11-3: Reaction of Alcohols with PBr3 485 11-10 Dehydration Reactions of Alcohols 487 Mechanism 11-4: (Review): Acid-Catalyzed Dehydration of an Alcohol 487 Problem-Solving Strategy: Proposing Reaction Mechanisms 491 11-11 Unique Reactions of Diols 494 Mechanism 11-5: The Pinacol Rearrangement 495  Contents xi 11-12 Esterification of Alcohols 496 11-13 Esters of Inorganic Acids 497 11-14 Reactions of Alkoxides 500 Key Mechanism 11-6:The Williamson Ether Synthesis 500 Problem-Solving Strategy: Multistep Synthesis 502 Summary: Reactions of Alcohols 505 Essential Terms 508 Study Problems 509 INFRARED SPECTROSCOPY AND 12 MASS SPECTROMETRY 513 12-1 Introduction 513 12-2 The Electromagnetic Spectrum 514 12-3 The Infrared Region 515 12-4 Molecular Vibrations 516 12-5 IR-Active and IR-Inactive Vibrations 518 12-6 Measurement of the IR Spectrum 519 12-7 Infrared Spectroscopy of Hydrocarbons 522 12-8 Characteristic Absorptions of Alcohols and Amines 527 12-9 Characteristic Absorptions of Carbonyl Compounds 528 12-10 Characteristic Absorptions of C—N Bonds 533 12-11 Simplified Summary of IR Stretching Frequencies 535 12-12 Reading and Interpreting IR Spectra (Solved Problems) 537 12-13 Introduction to Mass Spectrometry 541 12-14 Determination of the Molecular Formula by Mass Spectrometry 545 12-15 Fragmentation Patterns in Mass Spectrometry 548 Summary: Common Fragmentation Patterns 553 Essential Terms 555 Study Problems 556 NUCLEAR MAGNETIC RESONANCE 13 SPECTROSCOPY 563 13-1 Introduction 563 13-2 Theory of Nuclear Magnetic Resonance 563 13-3 Magnetic Shielding by Electrons 566 13-4 The NMR Spectrometer 567 13-5 The Chemical Shift 568 13-6 The Number of Signals 575 13-7 Areas of the Peaks 577 13-8 Spin-Spin Splitting 580 Problem-Solving Strategy: Drawing An NMR Spectrum 584 13-9 Complex Sitting 588 13-10 Stereochemical Nonequivalence of Protons 591 13-11 Time Dependence of NMR Spectroscopy 594 Problem-Solving Strategy: Interpreting Proton NMR Sectra 597 xii Contents 13-12 Carbon-13 NMR Spectroscopy 602 13-13 Interpreting Carbon NMR Spectra 609 13-14 Nuclear Magnetic Resonance Imaging 611 Problem-Solving Strategy: Spectroscopy Problems 612 Essential Terms 617 Study Problems 618 14 ETHERS, EPOXIDES, AND THIOETHERS 625 14-1 Introduction 625 14-2 Physical Properties of Ethers 626 14-3 Nomenclature of Ethers 630 14-4 Spectroscopy of Ethers 633 14-5 The Williamson Ether Synthesis 635 14-6 Synthesis of Ethers by Alkoxymercuration–Demercuration 636 14-7 Industrial Synthesis: Bimolecular Condensation of Alcohols 637 Summary: Syntheses of Ethers (Review) 638 14-8 Cleavage of Ethers by HBr and HI 638 Mechanism 14-1: Cleavage of an Ether by HBr or HI 639 14-9 Autoxidation of Ethers 641 Summary: Reactions of Ethers 641 14-10 Thioethers (Sulfides) and Silyl Ethers 642 14-11 Synthesis of Epoxides 646 Summary: Epoxide Syntheses 648 14-12 Acid-Catalyzed Ring Opening of Epoxides 649 Mechanism 14-2: Acid-Catalyzed Opening of Epoxides in Water 649 Mechanism 14-3: Acid-Catalyzed Opening of an Epoxide in an Alcohol Solution 650 14-13 Base-Catalyzed Ring Opening of Epoxides 652 Mechanism 14-4: Base-Catalyzed Opening of Epoxides 653 14-14 Orientation of Epoxide Ring Opening 654 14-15 Reactions of Epoxides with Grignard and Organolithium Reagents 656 14-16 Epoxy Resins: The Advent of Modern Glues 656 Summary: Reactions of Epoxides 658 Essential Terms 660 Study Problems 662 CONJUGATED SYSTEMS, ORBITAL SYMMETRY, 15 AND ULTRAVIOLET SPECTROSCOPY 667 15-1 Introduction 667 15-2 Stabilities of Dienes 667 15-3 Molecular Orbital Picture of a Conjugated System 669 15-4 Allylic Cations 673 15-5 1,2- and 1,4-Addition to Conjugated Dienes 674 Mechanism 15-1: 1,2- and 1,4-Addition to a Conjugated Diene 675  Contents xiii 15-6 Kinetic versus Thermodynamic Control in the Addition of HBr to Buta-1,3-diene 676 15-7 Allylic Radicals 678 Mechanism 15-2: Free-Radical Allylic Bromination 678 15-8 Molecular Orbitals of the Allylic System 680 15-9 Electronic Configurations of the Allyl Radical, Cation, and Anion 681 15-10 SN2 Displacement Reactions of Allylic Halides and Tosylates 683 15-11 The Diels–Alder Reaction 684 Key Mechanism 15-3:The Diels–Alder Reaction 684 15-12 The Diels–Alder as an Example of a Pericyclic Reaction 692 15-13 Ultraviolet Absorption Spectroscopy 696 15-14 Colored Organic Compounds 701 15-15 UV-Visible Analysis in Biology and Medicine 704 Essential Terms 706 Study Problems 708 16 AROMATIC COMPOUNDS 713 16-1 Introduction: The Discovery of Benzene 713 16-2 The Structure and Properties of Benzene 713 16-3 The Molecular Orbitals of Benzene 717 16-4 The Molecular Orbital Picture of Cyclobutadiene 720 16-5 Aromatic, Antiaromatic, and Nonaromatic Compounds 722 16-6 Hückel’s Rule 722 16-7 Molecular Orbital Derivation of Hückel’s Rule 725 16-8 Aromatic Ions 726 16-9 Heterocyclic Aromatic Compounds 731 16-10 Polynuclear Aromatic Hydrocarbons 735 16-11 Aromatic Allotropes of Carbon 737 16-12 Fused Heterocyclic Compounds 739 16-13 Nomenclature of Benzene Derivatives 740 16-14 Physical Properties of Benzene and Its Derivatives 742 16-15 Spectroscopy of Aromatic Compounds 743 Essential Terms 746 Study Problems 748 17 REACTIONS OF AROMATIC COMPOUNDS 756 17-1 Electrophilic Aromatic Substitution 756 Key Mechanism 17-1: Electrophilic Aromatic Substitution 757 17-2 Halogenation of Benzene 758 Mechanism 17-2: Bromination of Benzene 758 17-3 Nitration of Benzene 760 Mechanism 17-3: Nitration of Benzene 760 17-4 Sulfonation of Benzene 761 Mechanism 17-4: Sulfonation of Benzene 762 17-5 Nitration of Toluene: The Effect of Alkyl Substitution 763 xiv Contents 17-6 Activating, Ortho, Para-Directing Substituents 766 Summary: Activating, Ortho, Para-Directors 768 17-7 Deactivating, Meta-Directing Substituents 769 Summary: Deactivating, Meta-Directors 771 17-8 Halogen Substituents: Deactivating, but Ortho, Para-Directing 772 Summary: Directing Effects of Substituents 774 17-9 Effects of Multiple Substituents on Electrophilic Aromatic Substitution 774 17-10 The Friedel–Crafts Alkylation 777 Mechanism 17-5: Friedel–Crafts Alkylation 778 17-11 The Friedel–Crafts Acylation 781 Mechanism 17-6: Friedel–Crafts Acylation 782 Summary: Comparison of Friedel–Crafts Alkylation and Acylation 784 17-12 Nucleophilic Aromatic Substitution 786 Mechanism 17-7: Nucleophilic Aromatic Substitution (Addition–Elimination) 787 Mechanism 17-8: Nucleophilic Aromatic Substitution (Benzyne Mechanism) 789 17-13 Aromatic Substitutions Using Organometallic Reagents 790 17-14 Addition Reactions of Benzene Derivatives 796 Mechanism 17-9:The Birch Reduction 797 17-15 Side-Chain Reactions of Benzene Derivatives 798 17-16 Reactions of Phenols 802 Summary: Reactions of Aromatic Compounds 805 Essential Terms 808 Study Problems 810 18 KETONES AND ALDEHYDES 816 18-1 Carbonyl Compounds 816 18-2 Structure of the Carbonyl Group 817 18-3 Nomenclature of Ketones and Aldehydes 818 18-4 Physical Properties of Ketones and Aldehydes 820 18-5 Spectroscopy of Ketones and Aldehydes 822 18-6 Industrial Importance of Ketones and Aldehydes 828 18-7 Review of Syntheses of Ketones and Aldehydes 829 18-8 Synthesis of Ketones from Carboxylic Acids 833 18-9 Synthesis of Ketones and Aldehydes from Nitriles 833 18-10 Synthesis of Aldehydes and Ketones from Acid Chlorides and Esters 835 Summary: Syntheses of Ketones and Aldehydes 837 18-11 Reactions of Ketones and Aldehydes: Introduction to Nucleophilic Addition 839 Key Mechanism 18-1: Nucleophilic Additions to Carbonyl Groups 841 18-12 The Wittig Reaction 843 Mechanism 18-2: The Wittig Reaction 844 18-13 Hydration of Ketones and Aldehydes 847 Mechanism 18-3: Hydration of Ketones and Aldehydes 847  Contents xv 18-14 Formation of Cyanohydrins 849 Mechanism 18-4: Formation of Cyanohydrins 849 18-15 Formation of Imines 850 Key Mechanism 18-5: Formation of Imines 851 18-16 Condensations with Hydroxylamine and Hydrazines 853 Summary: Condensations of Amines with Ketones and Aldehydes 854 18-17 Formation of Acetals 855 Key Mechanism 18-6: Formation of Acetals 856 Problem-Solving Strategy: Proposing Reaction Mechanisms 858 18-18 Use of Acetals as Protecting Groups 860 18-19 Oxidation of Aldehydes 861 18-20 Reductions of Ketones and Aldehydes 862 Mechanism 18-7: Wolff–Kishner Reduction 864 Summary: Reactions of Ketones and Aldehydes 865 Essential Terms 868 Study Problems 870 19 AMINES 879 19-1 Introduction 879 19-2 Nomenclature of Amines 880 19-3 Structure of Amines 882 19-4 Physical Properties of Amines 884 19-5 Basicity of Amines 886 19-6 Effects on Amine Basicity 887 19-7 Salts of Amines 889 19-8 Spectroscopy of Amines 891 19-9 Reactions of Amines with Ketones and Aldehydes (Review) 895 19-10 Aromatic Substitution of Arylamines and Pyridine 896 Mechanism 19-1: Electrophilic Aromatic Substitution of Pyridine 897 Mechanism 19-2: Nucleophilic Aromatic Substitution of Pyridine 899 19-11 Alkylation of Amines by Alkyl Halides 899 19-12 Acylation of Amines by Acid Chlorides 900 Mechanism 19-3: Acylation of an Amine by an Acid Chloride 901 19-13 Formation of Sulfonamides 903 19-14 Amines as Leaving Groups: The Hofmann Elimination 904 Mechanism 19-4: Hofmann Elimination 904 19-15 Oxidation of Amines; The Cope Elimination 907 Mechanism 19-5: The Cope Elimination of an Amine Oxide 908 19-16 Reactions of Amines with Nitrous Acid 910 Mechanism 19-6: Diazotization of an Amine 910 19-17 Reactions of Arenediazonium Salts 911 Summary: Reactions of Amines 915 19-18 Synthesis of Amines by Reductive Amination 918 19-19 Synthesis of Amines by Acylation–Reduction 920 xvi Contents 19-20 Syntheses Limited to Primary Amines 922 Summary Synthesis of Amines 926 Essential Terms 929 Study Problems 931 20 CARBOXYLIC ACIDS 939 20-1 Introduction 939 20-2 Nomenclature of Carboxylic Acids 940 20-3 Structure and Physical Properties of Carboxylic Acids 943 20-4 Acidity of Carboxylic Acids 944 20-5 Salts of Carboxylic Acids 948 20-6 Commercial Sources of Carboxylic Acids 950 20-7 Spectroscopy of Carboxylic Acids 952 20-8 Synthesis of Carboxylic Acids 956 Summary: Syntheses of Carboxylic Acids 958 20-9 Reactions of Carboxylic Acids and Derivatives; Nucleophilic Acyl Substitution 960 Mechanism 20-1: Nucleophilic Acyl Substitution in the Basic Hydrolysis of an Ester 960 20-10 Condensation of Acids with Alcohols: The Fischer Esterification 961 Key Mechanism 20-2: Fischer Esterification 962 20-11 Esterification Using Diazomethane 965 Mechanism 20-3: Esterification Using Diazomethane 966 20-12 Condensation of Acids with Amines: Direct Synthesis of Amides 966 20-13 Reduction of Carboxylic Acids 967 20-14 Alkylation of Carboxylic Acids to Form Ketones 968 20-15 Synthesis and Use of Acid Chlorides 969 Summary: Reactions of Carboxylic Acids 972 Essential Terms 974 Study Problems 975 21 CARBOXYLIC ACID DERIVATIVES 981 21-1 Introduction 981 21-2 Structure and Nomenclature of Acid Derivatives 982 21-3 Physical Properties of Carboxylic Acid Derivatives 988 21-4 Spectroscopy of Carboxylic Acid Derivatives 991 21-5 Interconversion of Acid Derivatives by Nucleophilic Acyl Substitution 997 Key Mechanism 21-1: Addition–Elimination Mechanism of Nucleophilic Acyl Substitution 998 Mechanism 21-2: Conversion of an Acid Chloride to an Anhydride 1001 Mechanism 21-3: Conversion of an Acid Chloride to an Ester 1001 Mechanism 21-4: Conversion of an Acid Chloride to an Amide 1002 Mechanism 21-5: Conversion of an Acid Anhydride to an Ester 1002  Contents xvii Mechanism 21-6: Conversion of an Acid Anhydride to an Amide 1003 Mechanism 21-7: Conversion of an Ester to an Amide (Ammonolysis of an Ester) 1003 21-6 Transesterification 1006 Problem-Solving Strategy: Proposing Reaction Mechanisms 1007 Mechanism 21-8:Transesterification 1008 21-7 Hydrolysis of Carboxylic Acid Derivatives 1009 Mechanism 21-9: Saponification of an Ester 1010 Mechanism 21-10: Basic Hydrolysis of an Amide 1012 Mechanism 21-11: Acidic Hydrolysis of an Amide 1012 Mechanism 21-12: Base-Catalyzed Hydrolysis of a Nitrile 1014 21-8 Reduction of Acid Derivatives 1014 Mechanism 21-13: Hydride Reduction of an Ester 1015 Mechanism 21-14: Reduction of an Amide to an Amine 1016 21-9 Reactions of Acid Derivatives with Organometallic Reagents 1017 Mechanism 21-15: Reaction of an Ester with Two Moles of a Grignard Reagent 1018 21-10 Summary of the Chemistry of Acid Chlorides 1019 21-11 Summary of the Chemistry of Anhydrides 1020 21-12 Summary of the Chemistry of Esters 1023 21-13 Summary of the Chemistry of Amides 1027 21-14 Summary: of the Chemistry of Nitriles 1030 21-15 Thioesters 1031 21-16 Esters and Amides of Carbonic Acid 1032 Essential Terms 1035 Study Problems 1037 CONDENSATIONS AND ALPHA SUBSTITUTIONS 22 OF CARBONYL COMPOUNDS 1045 22-1 Introduction 1045 Mechanism 22-1: Alpha Substitution 1045 Mechanism 22-2: Addition of an Enolate to Ketones and Aldehydes (a Condensation) 1046 Mechanism 22-3: Substitution of an Enolate on an Ester (a Condensation) 1046 22-2 Enols and Enolate Ions 1046 Mechanism 22-4: Base-Catalyzed Keto–Enol Tautomerism 1047 Mechanism 22-5: Acid-Catalyzed Keto–Enol Tautomerism 1047 22-3 Alkylation of Enolate Ions 1050 22-4 Formation and Alkylation of Enamines 1051 22-5 Alpha Halogenation of Ketones 1054 Mechanism 22-6: Base-Promoted Halogenation 1054 Mechanism 22-7: Final Steps of the Haloform Reaction 1056 Mechanism 22-8: Acid-Catalyzed Alpha Halogenation 1058 22-6 Alpha Bromination of Acids: The HVZ Reaction 1059 22-7 The Aldol Condensation of Ketones and Aldehydes 1060 Key Mechanism 22-9: Base-Catalyzed Aldol Condensation 1061 Mechanism 22-10: Acid-Catalyzed Aldol Condensation 1063 xviii Contents 22-8 Dehydration of Aldol Products 1063 Key Mechanism 22-11: Base-Catalyzed Dehydration of an Aldol 1064 22-9 Crossed Aldol Condensations 1065 Problem-Solving Strategy: Proposing Reaction Mechanisms 1066 22-10 Aldol Cyclizations 1068 22-11 Planning Syntheses Using Aldol Condensations 1069 22-12 The Claisen Ester Condensation 1070 Key Mechanism 22-12: The Claisen Ester Condensation 1071 22-13 The Dieckmann Condensation: A Claisen Cyclization 1074 22-14 Crossed Claisen Condensations 1074 22-15 Syntheses Using b -Dicarbonyl Compounds 1077 22-16 The Malonic Ester Synthesis 1079 22-17 The Acetoacetic Ester Synthesis 1082 22-18 Conjugate Additions: The Michael Reaction 1085 Mechanism 22-13: 1,2-Addition and 1,4-Addition (Conjugate Addition) 1085 22-19 The Robinson Annulation 1088 Problem-Solving Strategy: Proposing Reaction Mechanisms 1089 Summary: Enolate Additions and Condensations 1092 Essential Terms 1094 Study Problems 1096 23 CARBOHYDRATES AND NUCLEIC ACIDS 1101 23-1 Introduction 1101 23-2 Classification of Carbohydrates 1102 23-3 Monosaccharides 1103 23-4 Erythro and Threo Diastereomers 1106 23-5 Epimers 1107 23-6 Cyclic Structures of Monosaccharides 1108 Mechanism 23-1: Formation of a Cyclic Hemiacetal 1108 23-7 Anomers of Monosaccharides; Mutarotation 1112 23-8 Reactions of Monosaccharides: Side Reactions in Base 1114 Mechanism 23-2: Base-Catalyzed Epimerization of Glucose 1115 Mechanism 23-3: Base-Catalyzed Enediol Rearrangement 1115 23-9 Reduction of Monosaccharides 1116 23-10 Oxidation of Monosaccharides; Reducing Sugars 1117 23-11 Nonreducing Sugars: Formation of Glycosides 1119 23-12 Ether and Ester Formation 1121 23-13 Reactions with Phenylhydrazine: Osazone Formation 1124 23-14 Chain Shortening: The Ruff Degradation 1125 23-15 Chain Lengthening: The Kiliani–Fischer Synthesis 1125 23-16 Determination of Ring Size; Periodic Acid Cleavage of Sugars 1128 Summary: Reactions of Sugars 1129 23-17 Disaccharides 1132 23-18 Polysaccharides 1136 23-19 Nucleic Acids: Introduction 1140  Contents xix 23-20 Ribonucleosides and Ribonucleotides 1141 23-21 The Structures of RNA and DNA 1143 23-22 Additional Functions of Nucleotides 1147 Essential Terms 1149 Study Problems 1151 24 AMINO ACIDS, PEPTIDES, AND PROTEINS 1155 24-1 Introduction 1155 24-2 Structure and Stereochemistry of the ␣-Amino Acids 1156 24-3 Acid–Base Properties of Amino Acids 1160 24-4 Isoelectric Points and Electrophoresis 1162 24-5 Synthesis of Amino Acids 1164 Summary: Syntheses of Amino Acids 1168 24-6 Resolution of Amino Acids 1169 24-7 Reactions of Amino Acids 1170 Summary: Reactions of Amino Acids 1172 24-8 Structure and Nomenclature of Peptides and Proteins 1173 24-9 Peptide Structure Determination 1177 24-10 Solution-Phase Peptide Synthesis 1182 24-11 Solid-Phase Peptide Synthesis 1185 24-12 Classification of Proteins 1190 24-13 Levels of Protein Structure 1190 24-14 Protein Denaturation 1193 Essential Terms 1195 Study Problems 1198 25 LIPIDS 1201 25-1 Introduction 1201 25-2 Waxes 1202 25-3 Triglycerides 1202 25-4 Saponification of Fats and Oils; Soaps and Detergents 1206 25-5 Phospholipids 1209 25-6 Steroids 1210 25-7 Prostaglandins 1213 25-8 Terpenes 1215 Essential Terms 1218 Study Problems 1219 26 SYNTHETIC POLYMERS 1222 26-1 Introduction 1222 26-2 Addition Polymers 1223 Mechanism 26-1: Free-Radical Polymerization 1225 Mechanism 26-2: Cationic Polymerization 1226 Mechanism 26-3: Anionic Polymerization 1228 xx Contents 26-3 Stereochemistry of Polymers 1229 26-4 Stereochemical Control of Polymerization; Ziegler–NattaCatalysts 1230 26-5 Natural and Synthetic Rubbers 1230 26-6 Copolymers of Two or More Monomers 1232 26-7 Condensation Polymers 1232 26-8 Polymer Structure and Properties 1236 Essential Terms 1239 Study Problems 1240 APPENDICES 1243 1A NMR: Proton Chemical Shifts 1244 1B NMR: Spin-Spin Coupling Constants 1246 1C NMR: Chemical Shifts in Organic Compounds 1247 2A IR: Characteristic Infrared Group Frequencies 1248 2B IR: Characteristic Infrared Absorptions of Functional Groups 1251 3A Methods and Suggestions for Proposing Mechanisms 1253 3B Suggestions for Developing Multistep Syntheses 1256 4 pKa Values for Representative Compounds 1257 Answers A1 Photo Credits PC1 Index I1  Contents xxi KEY MECHANISM BOXES CHAPTER 4 Free-Radical Halogenation 136 CHAPTER 6 The SN2 Reaction 247 The SN1 Reaction 258 The E1 Reaction 266 CHAPTER 7 Acid-Catalyzed Dehydration of an Alcohol 313 CHAPTER 8 Electrophilic Addition to Alkenes 330 CHAPTER 10 Grignard Reactions 443 CHAPTER 11 The Williamson Ether Synthesis 500 CHAPTER 15 The Diels–Alder Reaction 684 CHAPTER 17 Electrophilic Aromatic Substitution 757 CHAPTER 18 Nucleophilic Additions to Carbonyl Groups 841 Formation of lmines 851 Formation of Acetals 856 CHAPTER 20 Fischer Esterification 962 CHAPTER 21 Addition–Elimination Mechanism of Nucleophilic Acyl Substitution 998 CHAPTER 22 Base-Catalyzed Aldol Condensation 1061 Base-Catalyzed Dehydration of an Aldol 1064 The Claisen Ester Condensation 1071 MECHANISM BOXES CHAPTER 6 Allylic Bromination 228 Inversion of Configuration in the SN2 Reaction 244 Racemization in the SN1 Reaction 252 Hydride Shift in an SN1 Reaction 253 Methyl Shift in an SN1 Reaction 254 Rearrangement in an E1 Reaction 261 CHAPTER 7 Dehydrohalogenation by the E2 Mechanism 304 Stereochemistry of the E2 Reaction 306 E2 Debromination of a Vicinal Dibromide 310 CHAPTER 8 Ionic Addition of HX to an Alkene 332 Free-Radical Addition of HBr to Alkenes 334 Acid-Catalyzed Hydration of an Alkene 338 Oxymercuration of an Alkene 340 Hydroboration of an Alkene 345 Addition of Halogens to Alkenes 350 Formation of Halohydrins 352 Epoxidation of Alkenes 360 Acid-Catalyzed Opening of Epoxides 362 Olefin Metathesis 376 CHAPTER 9 Metal–Ammonia Reduction of an Alkyne 407 Acid-Catalyzed Keto–Enol Tautomerism 411 Base-Catalyzed Keto–Enol Tautomerism 413 xxii Contents MECHANISM BOXES (continued) CHAPTER 10 Hydride Reduction of a Carbonyl Group 454 CHAPTER 11 Reaction of a Tertiary Alcohol with HBr (SN1) 480 Reaction of a Primary Alcohol with HBr (SN2) 480 Reaction of Alcohols with PBr3 485 (Review): Acid-Catalyzed Dehydration of an Alcohol 487 The Pinacol Rearrangement 495 CHAPTER 14 Cleavage of an Ether by HBr or HI 639 Acid-Catalyzed Opening of Epoxides in Water 649 Acid-Catalyzed Opening of an Epoxide in an Alcohol Solution 650 Base-Catalyzed Opening of Epoxides 653 CHAPTER 15 1,2- and 1,4-Addition to a Conjugated Diene 675 Free-Radical Allylic Bromination 678 CHAPTER 17 Bromination of Benzene 758 Nitration of Benzene 760 Sulfonation of Benzene 762 Friedel–Crafts Alkylation 778 Friedel–Crafts Acylation 782 Nucleophilic Aromatic Substitution (Addition–Elimination) 787 Nucleophilic Aromatic Substitution (Benzyne Mechanism) 789 The Birch Reduction 797 CHAPTER 18 The Wittig Reaction 844 Hydration of Ketones and Aldehydes 847 Formation of Cyanohydrins 849 Wolff–Kishner Reduction 864 CHAPTER 19 Electrophilic Aromatic Substitution of Pyridine 897 Nucleophilic Aromatic Substitution of Pyridine 899 Acylation of an Amine by an Acid Chloride 901 Hofmann Elimination 904 The Cope Elimination of an Amine Oxide 908 Diazotization of an Amine 910 CHAPTER 20 Nucleophilic Acyl Substitution in the Basic Hydrolysis of an Ester 960 Esterification Using Diazomethane 966 CHAPTER 21 Conversion of an Acid Chloride to an Anhydride 1001 Conversion of an Acid Chloride to an Ester 1001 Conversion of an Acid Chloride to an Amide 1002 Conversion of an Acid Anhydride to an Ester 1002 Conversion of an Acid Anhydride to an Amide 1003 Conversion of an Ester to an Amide (Ammonolysis of an Ester) 1003 Transesterification 1008 Saponification of an Ester 1010 Basic Hydrolysis of an Amide 1012 Acidic Hydrolysis of an Amide 1012  Contents xxiii MECHANISM BOXES (continued) Base-Catalyzed Hydrolysis of a Nitrile 1014 Hydride Reduction of an Ester 1015 Reduction of an Amide to an Amine 1016 Reaction of an Ester with Two Moles of a Grignard Reagent 1018 CHAPTER 22 Alpha Substitution 1045 Addition of an Enolate to Ketones and Aldehydes (a Condensation) 1046 Substitution of an Enolate on an Ester (a Condensation) 1046 Base-Catalyzed Keto–Enol Tautomerism 1047 Acid-Catalyzed Keto–Enol Tautomerism 1047 Base-Promoted Halogenation 1054 Final Steps of the Haloform Reaction 1056 Acid-Catalyzed Alpha Halogenation 1058 Acid-Catalyzed Aldol Condensation 1063 1,2-Addition and 1,4-Addition (Conjugate Addition) 1085 CHAPTER 23 Formation of a Cyclic Hemiacetal 1108 Base-Catalyzed Epimerization of Glucose 1115 Base-Catalyzed Enediol Rearrangement 1115 CHAPTER 26 Free-Radical Polymerization 1225 Cationic Polymerization 1226 Anionic Polymerization 1228  New to this Edition  Cutting-edge coverage of organometallic reactions  Chapter Goals (Learning Outcomes) added to and reagents includes the palladium-catalyzed each chapter align with the Essential Problem- Suzuki and Heck reactions that were recognized by Solving Skills at the end of each chapter as well as the 2010 Nobel Prize in Chemistry. New discussions the Study Problems in the text and in of carbon-carbon bond formation, including MasteringChemistry. organometallic reagents in addition to reducing agents like DIBAL-H, are presented in a manner that  Nomenclature has been updated selectively to introductory students can understand. reflect the latest IUPAC naming convention standards.  Modern methods of oxidizing alcohols like Dess- Martin and Swern oxidations are explained by a  A new visual format throughout ensures unifying mechanism that covers the major methods consistency in the art, helping students make visual to oxidize alcohols to aldehydes and ketones connections between concepts and enhancing their (Chapter 11). accurate understanding of the figures.  Additional coverage on silyl ethers addresses their Approximately 100 new problems have been use as protecting groups for alcohols and added, both within the chapters and in the Study carbohydrates. Problems at the ends of the chapters.  A new section on colored compounds is added in New sections and notes of interest to biology Chapter 15, including natural and synthetic dyes, and majors and premedical students have been also a new section on biochemical and clinical added throughout, including a new section on applications of UV-visible spectroscopy. clinical analysis, as well as numerous applications relating to cancer and toxicology, green chemistry, biochemistry, and medicine. xxiv Preface To the Student As you begin your study of organic chemistry, you might feel overwhelmed by the number of compounds, names, reactions, and mechanisms that confront you. You might even won- der whether you can learn all this material in a single year. The most important function of a textbook is to organize the material to show that most of organic chemistry consists of a few basic principles and many extensions and applications of these principles. Relatively little memorization is required if you grasp the major concepts and develop flexibility in applying those concepts. Frankly, I have a poor memory, and I hate memorizing lists of information. I don’t remember the specifics of most of the reactions and mechanisms in this book, but I can work them out by remembering a few basic principles, such as “alcohol dehydrations usually go by E1 mechanisms.” Still, you’ll have to learn some facts and fundamental principles to serve as the work- ing “vocabulary” of each chapter. As a student, I learned this the hard way when I made a D on my second organic chemistry exam. I thought organic would be like general chemistry, where I could memorize a couple of equations and fake my way through the exams. For example, in the ideal gas chapter, I would 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 to point out a small number of important facts and principles that should be learned to prepare for solving problems. For example, of the hun- dreds of reaction mechanisms shown in this book, about 20 are the fundamental mechanis- tic steps that combine into the longer, more complicated mechanisms. I’ve highlighted these fundamental mechanisms in Key Mechanism boxes to alert you to their importance. Spec- troscopy is another area where a student might feel pressured to memorize hundreds of facts, such as NMR chemical shifts and infrared vibration frequencies. I couldn’t do that, so I’ve always gotten by with knowing about a dozen NMR chemical shifts and about a dozen IR vibration frequencies, and knowing how they are affected by other influences. I’ve listed those important infrared frequencies in Table 12-2 and the important NMR chem- ical shifts in Table 13-3. Don’t try to memorize your way through this course. It doesn’t work; you have to know what’s going on so you can apply the material. Also, don’t think (like I did) that you can get by without memorizing anything. Read the chapter, listen carefully to the lectures, and work the problems. The problems will tell you whether or not you know the material. If you can do the problems, you should do well on the exams. If you can’t do the problems, you probably won’t be able to do the exams, either. If you keep having to look up an item to do the problems, that item is a good one to learn. Here are some hints I give my students at the beginning of the course: 1. Read the material in the book before the lecture (expect 13–15 pages per lecture). Knowing what to expect and what is in the book, you can take fewer notes and spend more time listening and understanding the lecture. 2. After the lecture, review your notes and the book, and do the in-chapter problems. Also, read the material for the next lecture. 3. If you are confused about something, visit your instructor during office hours immediately, before you fall behind. Bring your attempted solutions to problems with you to show the instructor where you are having trouble. 4. To study for an exam, begin by reviewing each chapter and your notes, then con- centrate on the end-of-chapter problems. Also use old exams for practice, if available. Many students find that working in a study group and posing problems for each other is particularly helpful. xxv xxvi Preface Remember the two “golden rules” of organic chemistry. 1. Don’t Get Behind! The course moves too fast, and it’s hard to catch up. 2. Work Lots of Problems. Everyone needs the practice, and the problems show where you need more work. I am always interested to hear from students using this book. If you have any suggestions about how the book might be made better, or if you’ve found an error, please let me know (L. G. Wade, Whitman College, Walla Walla, WA 99362: E-mail [email protected]). I take students’ suggestions seriously, and hundreds of them now appear in this book. For exam- ple, Whitman student Brian Lian suggested Figure 21-9, and University of Minnesota student (and race-car driver) Jim Coleman gave me the facts on the use of methanol at Indianapolis. Good luck with your study of organic chemistry. I’m certain you will enjoy this course, especially if you let yourself relax and develop an interest in how organic compounds influ- ence our lives. My goal in writing this book has been to make the process a little easier: to build the concepts logically on top of each other, so they flow naturally from one to the next. The hints and suggestions for problem solving have helped my students in the past, and I hope some of them will help you to learn and use the material. Even if your memory is worse than mine (highly unlikely), you should be able to do well in organic chemistry. I hope this will be a good learning experience for all of us. To the Instructor In writing the first edition of this text, my goal was to produce a modern, readable text that uses the most effective techniques of presentation and review. I wanted a book that presents organic chemistry at the level needed for chemistry and biochemistry majors, but one that presents and explains the material in ways that facilitate success for all the many different kinds of students who take the course. Subsequent editions have extended and refined these goals, with substantial rewriting and reorganizing and with many new features. This eighth edition incorporates even more refinements than the seventh edition with revisions in the organization, writing, and graphics. NEW TO THIS EDITION In order to help students navigate the material and study more effectively, summarized Chapter Goals have been added to the start of each chapter to reflect the major focus and breadth of the chapter content. Revised Essential Problem-Solving Skills at the end of each chapter reinforce the Chapter Goals and provide students with a guide to major take-away skills they need from each chapter. New problem references with the Essential Problem-Solving Skills enable students to identify which in-chapter and end-of-chapter problems will help them master each of the skills. Updated Applications, including cases relating to cancer and toxicology, green chemistry, bio- chemistry, and medicine, now have descriptive titles to help students understand the relevance of an example to what they are learning in the text. Contemporary content has been updated throughout, including the palladium catalyzed Suzuki and Heck reac- tions, biochemical and clinical applications of UV-visible spectroscopy, a brief intro- duction to graphene, and the use of silyl ethers as a protecting group for alcohols ensuring that this edition is the most up-to-date organic chemistry resource possible. A revised visual program helps students make visual and accurate connections between concepts and from one figure to the next. KEY FEATURES Up-to-Date Treatment: In addition to the classical reactions, this book covers many techniques and reactions that have more recently gained wide use among practicing chemists. Molecular-orbital theory is included early and used to explain electronic effects in conjugated and aromatic systems, pericyclic reactions, and ultraviolet spectroscopy. Carbon-13 NMR spectroscopy is treated as the routine tool it has become in most research laboratories, and the DEPT technique is included in this edition. Many of the newer  Preface xxvii synthetic techniques are also included, such as Suzuki coupling and the Heck reaction, asymmetric hydrogenation and epoxidation, reductions using DIBAL-H, olefin metathe- sis, silyl ether protecting groups, and oxidations using chromium-free reagents such as the Swern and Dess–Martin oxidations. Reaction Mechanisms: Reaction mechanisms are important in all areas of organic chem- istry, but they are difficult for many students. Students fall into the trap of memorizing a mechanism while not understanding why it proceeds as it does. This book stresses the prin- ciples used to predict mechanisms. Problem-solving sections develop basic techniques for approaching mechanism problems, and they work to minimize rote memorization. These techniques emphasize deciding whether the reaction is acidic, basic, or free radical in nature, then breaking it down into Lewis acid–base interactions and using “electron pushing arrows” to illustrate these individual steps. Important mechanisms are high- lighted by placing them in the Mechanism and Key Mechanism boxes. Introduction to Mechanisms Using Free-Radical Halogenation: The advantages and disadvantages of using free-radical halogenation to introduce reaction mechanisms have been debated for many years. The principal objection to free-radical halogenation is that it is not a useful synthetic reaction. But useful reactions such as nucleophilic substitution and additions to alkenes are complicated by participation of the solvent and other effects. Gas-phase free-radical halogenation allows a clearer treatment of kinetics and thermo- dynamics, as long as its disadvantages as a synthetic reaction are discussed and students are aware of the limitations. Organic Synthesis: Organic synthesis is stressed throughout this book, with progressive discussions of the process involved in developing a synthesis. Retrosynthetic analysis is emphasized, and the student learns to work backward from the target compound and forward from the starting materials to find a common intermediate. Typical yields have been provided for many synthetic reactions, although I hope stu- dents will not misuse these numbers. Too often students consider the yield of a reaction to be a fixed characteristic just as the melting point of a compound is fixed. In practice, many factors affect product yields, and literature values for apparently similar reactions often differ by a factor of 2 or more. The yields given in this book are typical yields that a good student with excellent technique might obtain. Spectroscopy: Spectroscopy is one of the most important tools of the organic chemist. This book develops the theory for each type of spectroscopy and then discusses the char- acteristic spectral features. The most useful and dependable characteristics are summarized into a small number of rules of thumb that allow the student to interpret most spectra with- out looking up or memorizing large tables of data. For reference use, extensive tables of NMR and IR data are provided as appendices. This approach is particularly effective with IR and NMR spectroscopy, and with mass spectrometry. Practical rules are given to help students see what information is available in the spectrum and what spectral characteristics usually correspond to what structural features. Sam- ple problems and Study Problems located throughout the text show how the clues from various spectra are combined to propose a structure. The emphasis is on helping students develop an intu- itive feel for using spectroscopy to solve structural problems. A comprehensive list of the spec- troscopy problems found in each chapter is available online a www.pearsonhighered.com. Nomenclature: The most recent IUPAC nomenclature is stressed throughout the book, but common nomenclature is also discussed and used to develop students’ familiarity. Teach- ing only the IUPAC nomenclature might be justifiable in theory, but such an approach would handicap students in their further study and use of the literature. Much of the literature of chemistry, biology, and medicine uses common names such as methyl ethyl ketone, isovaleric acid, methyl tert-butyl ether, g-aminobutyric acid, and e-caprolactam. This book emphasizes why systematic nomenclature is often preferred, yet it encourages familiarity with common names as well. xxviii Preface Key Mechanism Boxes 20 Key Mechanism Boxes are the fundamental mechanistic principles that recur throughout the course. They are the mech- anisms that compose most of the longer, more complex mecha- nisms. Each Key Mechanism Box reinforces student understanding with steps and explanations that describe the the reaction mechanism (how the reaction occurs), a specific exam- ple of the mechanism for reinforcement, and a concluding prob- lem or question so students can assess their understanding. Mechanism Boxes 150 Mechanism Boxes help students understand how reactions occur by focusing on the individual steps of each reaction. The Mechanism Boxes are shaded in blue so students can locate them easily as they thumb through the chapter. Multi-Part Problems Over 1400 (mostly multi-part) problems provide immediate review and reinforcement as students learn the material and make sure they understand each section well enough before moving on to the next.  Preface xxix Problem Solving Strategies Problem-Solving Strategies help students break down the multitude of complex problems into simpler pieces and help students establish thoughtful methods for approach- ing complicated problems–like those that require proposing mech- anisms and developing multi-step synthesis. Problem Solving Hints Problem Solving Hints appear in the margins and remind students of facts or princi- ples that may be useful for solving common types of problems. They are the tips the author gives his own students to help them work problems and reviews for exams. Application Boxes Application Boxes throughout demonstrate the relevance of Organic Chemistry to students’ lives and areas of interest including contemporary topics such as Bio- chemistry, Drugs, Environment, Medicine, Fuels, and Green Chemistry. xxx Preface Chapter Goals and Essential Problem Solving Skills Enhanced pedagogical tools including Chapter Goals and Essential Problem Solving Skills help students navigate the material and assess their under- standing and proficiency throughout each chapter. Professors can use these features at-a-glance to assign homework related to specific skills (also available in MasteringChemistry) while students can study more effectively by solving problems directly tied to chapter goals. Summary Summary Feature: The Summaries, located in key locations throughout the chapters high- light important information using charts and graphs when possible. Resources in Print and Online Supplement Available in Available Instructor or Description Print? Online? Student Supplement MasteringChemistry® ✓ Instructor and Student MasteringChemistry from Pearson has been designed and refined with a Supplement single purpose in mind: to help educators create that moment of understanding with their students. The Mastering platform delivers engaging, dynamic learning opportunities—focused on your course objectives and responsive to each student’s progress—that are proven to help students absorb course material and understand difficult concepts. By complementing your teaching with our engaging technology and content, you can be confident your students will arrive at that moment—the moment of true understanding. (Available at www.masteringchemistry.com) Solutions Manual ✓ Instructor and Student This Solutions Manual provides detailed solutions to all in-chapter as well by Jan William Simek Supplement as the end-of-chapter exercises in the text. IRDVD ✓ ✓ Instructor Supplement This resource provides an integrated collection of resources to help instructors make efficient and effective use of their time. This DVD features all artwork from the text, including figures and tables in PDF format for high- resolution printing, as well as four pre-built PowerPoint™ presentations. The first presentation contains the images embedded within PowerPoint slides. The second includes a complete lecture outline that is modifiable by the user. The final two presentations contain worked “in chapter” sample exercises and questions to be used with classroom iClicker systems. This DVD also contains movies, animations, and electronic files of the Instructor’s Resource Manual, as well as the Test bank. Testbank ✓ ✓ Instructor Supplement This testbank contains over 3000 multiple-choice, true/false and matching questions. It is available in print format, in the TestGen program, in word format and in included in the item library of MasteringChemistry.. Organic Molecular Kit ✓ Instructor and Student Darling Models™ contain various pieces used to build atoms, bonds, and (Darling) Supplement molecules. This model kit allows you to build molecules and see the three- dimensional aspects of organic chemistry that can only be imagined in a two-dimensional drawing. Prentice Hall Molecular ✓ Instructor and Student The Prentice Hall molecular model set allows you to build space-filling and Model Kit for Organic Supplement ball-and-stick models of organic molecules. The components are precision- Chemistry tooled from quality plastics, are virtually indestructible, and come in a sturdy plastic case for easy storage. Provides a useful Instruction Book—with photos, diagrams, and concise discussions of chemical principles. xxxi Extend Learning Beyond the Classroom NEW for this edition! MasteringChemistry® leads students through the process of solving problems while promoting their understanding of chemical concepts. This assessment and tutorial program supplies quantifiable metrics and enables professors to compare their class performance against the national average on specific questions or topics. At a glance, professors can see class distribution of grades, time spent, most difficult problems, most difficult steps, and even the most common answer. Student Tutorial MasteringChemistry® tutorials guide students through the toughest topics in organic chem- istry with self-paced tutorials that provide individualized coaching. These assignable, in- depth tutorials are designed to coach students with hints and feedback specific to their indi- vidual misconceptions. Molecular Drawing Tool MasteringChemistry’s new molecular drawing tool accommodates the diversity of structures and reaction mechanisms inherent to organic chemistry while providing students with error-specific feedback. A comprehensive tutorial on drawing with MarvinSketch within Mastering helps students get up and running quickly on their homework. The drawing tool supports Lewis structures, skeletal structures, and complex mechanisms/arrow pushing and evaluates multiple aspects of the student-created structures in order to provide the most precise feedback possible. MasteringChemistry allows students to draw reaction mechanisms in a step-wise manner. Ranging in difficulty levels, the new mechanism problem types provide stu- dents with detailed, immediate feedback after each step of their mechanism or, if assigned, feedback after com- pletion of an entire multipart mechanism as to where they made their first mistake. Professors maintain con- trol over the grade value of each mechanistic step and can limit student attempts as well as assign a more challenging mechanistic problem for credit alone. Every individual student attempt is recorded within the grade- book and can be accessed by professors as they work with students to identify their misconceptions. xxxii  Extend Learning Beyond the Classroom xxxiii MasteringChemistry® End of Chapter Problems Almost all Study Problems from the Eighth Edition of Wade are available within MasteringChemistry and can be automatically graded and assigned for homework or practice. A robust, additional problem set associated with each chapter in Wade can also be assigned to encourage students to apply their knowledge to new problems and provide an excellent source for quiz questions. Gradebook Every assignment is automatically graded. At a glance, shades of red highlight vulnerable students and chal- lenging assignments. Gradebook Diagnostics Gradebook Diagnostics provide unique insight into class and student performance. With a single click, charts summarize the most difficult problems, vulnera- ble students, grade distribution, and score improve- ment over the duration of the course. Chapter-by-Chapter Changes Every chapter begins with Chapter Goals and ends with Essential Problem-Solving Skills, including references to particular end-of-chapter problems that reinforce each skill. New problems, Problem-Solving Hints, Essential Terms, and Applications have been added to almost every chapter. All IUPAC names have been updated to current IUPAC recommendations. Chapter 1 protecting groups earlier than acetals in Chapter 18. The section on acidity has been revised to include Problems using silyl ether chemistry reinforce the inductive effects of substituents on the acidity of concept. carboxylic acids, in addition to resonance effects and Sharpless Asymmetric Epoxidation (Nobel Prize 2001) is electronegativity. presented in a problem. Chapter 2 Chapter 15 The section on solubility has been expanded to A new section, Colored Organic Compounds, has been emphasize the role of hydrogen bonding and molecular added to explain how the HOMO-LUMO concept of size in the role of water solubility of organic molecules. highly conjugated molecules leads to absorption in the visible region, and how that applies to natural products, Chapter 3 dyes, pH indicators, and food colors. New problems show the student how to interconvert and A new section, UV-Visible Analysis in Biology and name structural formulas and Newman projections. Medicine, has been added to introduce UV analysis in Chapter 5 biochemistry, and to show the structural features of biological molecules that are responsible for UV The different types of chemical notation used to indicate absorption. An example of a reagent used in a clinical the three-dimensional spatial arrangement of bonds analyzer that undergoes a color change when changed by around carbon have been presented. alkaline phosphatase demonstrates how organic chemical Chapter 8 principles are used directly in medical technology. Dihydroxylation has been updated to emphasize catalytic Chapter 16 methods. A new description of graphene (Nobel Prize 2010 in Chapter 9 Physics) has been added in the section on Fullerenes (Nobel Prize 1996) and nanotubes. New problems emphasizing synthesis and identification of unknown structures have been added. Chapter 17 Chapter 11 A new section, Aromatic Substitutions Using Organometallic Reagents, has been added. In addition to Newer methods of alcohol oxidation (Swern, expanding the discussion of organocuprate reagents, new Dess–Martin) are introduced as environmentally discussions of the Heck reaction and Suzuki coupling preferable to the older chromium methods, including a (Nobel Prize 2010) are introduced, including methods of description of a general, unifying mechanism of alcohol preparing boronic acids and esters for the Suzuki oxidation to aldehydes and ketones. TEMPO is shown as reaction. Several problems illustrating these reactions in an oxidation catalyst to enhance hypochlorite oxidation. synthesis are included. Chapter 12 Chapter 18 An Application on the MALDI technique for mass The chemistry of 1,3-dithianes has been deleted. spectral analysis of biological molecules has been added. The use of DIBAL-H to reduce nitriles to aldehydes has Chapter 14 been added, as has the low-temperature reduction of A new section covers the formation and cleavage of silyl esters with DIBAL-H to produce aldehydes. Several ethers, and their strategy and use as protecting groups on problems have been added that include these reactions alcohols. This new material introduces the concept of in synthesis. xxxiv  Chapter-by-Chapter Changes xxxv Chapter 19 Chapter 23 The use of amine salts as phase-transfer catalysts has been The use of silyl ethers of carbohydrates to alter the deleted. solubility properties is incorporated in problems. Hofmann rearrangement of amides has been deleted. The Fischer proof of glucose has been condensed to an extended problem. Chapter 21 Newly added reactions are DIBAL-H reduction of esters, and Chapter 26 dialkylcuprate reaction with acid chlorides to produce ketones. Ring-opening metathesis polymerization (ROMP) has been demonstrated in a problem. Acknowledgments I am pleased to thank the many talented people who helped with this revision. More than anyone else, Jan William Simek, author of the Solutions Manual, has consistently provided me with excellent advice and sound judgment through several editions of this book. In this edition, Jan provided input on all of the chapter revisions, and helped to write and edit all of the new sections. He also co- authored most of the new problems and all of the Answers to Selected Problems. Particular thanks are also due to Developmental Editor John Murdzek, who made thousands of useful suggestions throughout the writing and revision process, and who helped to shape this new edition. I would like to thank the reviewers for their valuable insight and commentary. Although I did not adopt all their sug- gestions, most of them were helpful and contributed to the quality of the final product. Eighth Edition Accuracy Reviewers David A. Boyajian Palomar College Hasan Palandoken California Polytechnic State University Susan Schelbe Metro State College of Denver Alline Somlai Delta State University Eighth Edition Prescriptive Reviewers Jon Antilla University of South Florida Eric Brown Loyola University Lake Shore Timothy B Clark Western Washington University James Fletcher Creighton University Hasan Palandoken California Polytechnic State University Keith Osbourne Pascoe Georgia State University Anthony J Pearson Case Western Reserve Owen Priest Northwestern University K.C. Russell Northern Kentucky University Alline Somlai Delta State University Solomon Weldegirma University of South Florida Reviewers of Previous Editions Jung-Mo Ahn University of Texas at Dallas David Alonso Andrews University Merritt B. Andrus Brigham Young University Arthur J. Ashe University of Michigan Bill Baker University of South Florida Dan Becker Loyola University John Berger Montclair State University Bob Bly University of South Carolina Mary Boyd Loyola University, Chicago Hindy Bronstein Fordham College at Lincoln Center David Brown St. John’s University xxxvi Chapter-by-Chapter Changes Philip Brown North Carolina State University Christine Brzezowski University of Alberta Patrick Buick Florida Atlantic University David Cantillo Hillsborough Community College Dee Ann Casteel Bucknell University Amber Charlebois William Paterson University Cai Chengzhi University of Houston Barry Coddens Northwestern University Jamie Lee Cohen Pace University Barbara Colonna University of Miami Richard Conley Middlesex County College Robert Crow St. Louis College of Pharmacy Maria de GracaVicente Louisiana State University Chris Gorman North Carolina State University Geneive Henry Susquehanna University William Jenks Iowa State University Przemyslaw Maslak Pennsylvania State University Kristen Meisenheimer Cal Polytechnic at San Luis Obispo Stephen A. Miller University of Florida Guillermo Moyna University of the Sciences in Philadelphia Rabi Musah University at Albany Anthony J. Pearson CaseWestern Reserve University Allan Pinhas University of Cincinnati Stanley Raucher University ofWashington Suzanne Ruder Virginia Commonwealth University David Son Southern Methodist University Joseph B. Wachter Michigan State University Finally, I want to thank the people at Pearson, whose dedication and flexibility contributed to the completion of this project. Executive Editor, Jeanne Zalesky and Senior Project Editor, Jennifer Hart kept the project moving, ensured the needed resources were available, and made many useful comments and suggestions. Project Managers Marisa Taylor, Kate Thomas, and Shari Toron who kept the production process organized, on track, and on schedule. It has been a pleasure working with all these thoroughly professional and competent people. I’ve enjoyed working on this new edition, and I hope that it is an improved fine-tuning of the seventh edition. I’ve tried to make this book as error-free as possible, but I’m sure some errors have slipped by. If you find errors, or have suggestions about how the book might be made better, please let me know (L. G. Wade, Whitman College, Walla Walla, WA 99362; e-mail: [email protected]). Errors can be fixed quickly in the next print- ing. I’ve already started a file of possible changes and improvements for the next edition, and I hope many of the current users will contribute suggestions to this file. I hope this book makes your job easier and helps more of your students to succeed. That’s the most important reason why I wrote it. L. G. Wade, Jr. Walla Walla, Washington  1 Introduction and Review px pz py pz px GOALS FOR py CHAPTER 1  Review concepts from general chemistry that are essen-  Draw and interpret the types of structural formulas tial for success in organic chemistry, such as the electronic commonly used in organic chemistry, including condensed structure of the atom, Lewis structures and the octet rule, structural formulas and line–angle formulas. types of bonding, electronegativity, and formal charges.  Identify acids, bases, electrophiles, and nucleophiles.  Predict patterns of covalent and ionic bonding involv- Compare their strengths and predict their reactions based ing C, H, O, N, and the halogens. Identify resonance- on structure and bonding, as well as Ka and pKa values. stabilized structures and compare the relative importance of their resonance forms. 1-1 The modern definition of organic chemistry is the chemistry of carbon compounds. What is so special about carbon that a whole branch of chemistry is devoted to its com- The Origins of pounds? Unlike most other elements, carbon forms strong bonds to other carbon atoms Organic Chemistry and to a wide variety of other elements. Chains and rings of carbon atoms can be built up to form an endless variety of molecules. It is this diversity of carbon compounds that provides the basis for life on Earth. Living creatures are composed largely of com- plex organic compounds that serve structural, chemical, or genetic functions. The term organic literally means “derived from living organisms.” Originally, the science of organic chemistry was the study of compounds extracted from living organ- isms and their natural products. Compounds such as sugar, urea, starch, waxes, and plant oils were considered “organic,” and people accepted Vitalism, the belief that nat- ural products needed a “vital force” to create them. Organic chemistry, then, was the study of compounds having the vital force. Inorganic chemistry was the study of gases, rocks, and minerals, and the compounds that could be made from them. In the nineteenth century, experiments showed that organic compounds could be syn- thesized from inorganic compounds. In 1828, the German chemist Friedrich Wöhler converted ammonium cyanate, made from ammonia and cyanic acid, to urea simply by heating it in the absence of oxygen. The AbioCor self-contained artificial O heart, which was first implanted into a heat