Organic Chemistry, Eighth Edition PDF

Organic Chemistry EIGHTH EDITION Paula Yurkanis Bruice University Of California Santa Barbara Editor in Chief: Jeanne Zalesky Senior Acquisitions Editor: Chris Hess Product Marketing Manager: Elizabeth Ellsworth Project Manager: Elisa Mandelbaum Program Manager: Lis...

Organic Chemistry EIGHTH EDITION Paula Yurkanis Bruice University Of California Santa Barbara Editor in Chief: Jeanne Zalesky Senior Acquisitions Editor: Chris Hess Product Marketing Manager: Elizabeth Ellsworth Project Manager: Elisa Mandelbaum Program Manager: Lisa Pierce Editorial Assistant: Fran Falk Marketing Assistant: Megan Riley Executive Content Producer: Kristin Mayo Media Producer: Lauren Layn Director of Development: Jennifer Hart Development Editor: Matt Walker Team Lead, Program Management: Kristen Flathman Team Lead, Project Management: David Zielonka Production Management: GEX Publishing Services Compositor: GEX Publishing Services Art Specialist: Wynne Au Yeung Illustrator: Imagineering Text and Image Lead: Maya Gomez Text and Image Researcher: Amanda Larkin Design Manager: Derek Bacchus Interior and Cover Designer: Tamara Newnam Operations Specialist: Maura Zaldivar-Garcia Cover Image Credit: OlgaYakovenko/Shutterstock Copyright © 2016, 2014, 2011, 2007, 2004, 2001 Pearson Education, Inc. All Rights Reserved. Printed 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 otherwise. For information regarding permissions, request forms and the appropriate contacts within the Pearson Education Global Rights & Permissions department, please visit www.pearsoned.com/permissions/. Credits and acknowledgments of third party content appear on page C-1 which constitutes an extension of this copyright page. 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. Library of Congress Cataloging-in-Publication Data Bruice, Paula Yurkanis Organic chemistry / Paula Yurkanis Bruice, University of California, Santa Barbara. Eighth edition. | Upper Saddle River, NJ: Pearson Education, Inc., 2015. | Includes index. LCCN 2015038746 | ISBN 9780134042282 | ISBN 013404228X LCSH: Chemistry, Organic—Textbooks. LCC QD251.3.B78 2015 | DDC 547--dc23 LC record available at http://lccn.loc.gov/2015038746 ISBN 10: 0-13-404228-X; ISBN 13: 978-0-13-404228-2 (Student edition) ISBN 10: 0-13-406659-6; ISBN 13: 978-0-13-406659-2 (Instructor’s Review Copy) 1 2 3 4 5 6 7 8 9 10—CRK—16 15 14 13 12 www.pearsonhighered.com To Meghan, Kenton, and Alec with love and immense respect and to Tom, my best friend  Brief Table of Contents Preface xxii CH APTER 1 Remembering General Chemistry: Electronic Structure and Bonding 2 CH APTER 2 Acids and Bases: Central to Understanding Organic Chemistry 50 T U TO R IAL Acids and Bases 80 CH APTER 3 An Introduction to Organic Compounds: Nomenclature, Physical Properties, and Structure 88 T U TO R IAL Using Molecular Models 142 CH APTER 4 Isomers: The Arrangement of Atoms in Space 143 TU TO R IAL Interconverting Structural Representations 187 CH APTER 5 Alkenes: Structure, Nomenclature, and an Introduction to Reactivity Thermodynamics and Kinetics 190 T U TO R IAL Drawing Curved Arrows 225 CH APTER 6 The Reactions of Alkenes The Stereochemistry of Addition Reactions 235 CH APTER 7 The Reactions of Alkynes An Introduction to Multistep Synthesis 288 CH APTER 8 Delocalized Electrons: Their Effect on Stability, pKa, and the Products of a Reaction Aromaticity and Electronic Effects: An Introduction to the Reactions of Benzene 318 T U TO R IAL Drawing Resonance Contributors 382 CH APTER 9 Substitution and Elimination Reactions of Alkyl Halides 391 CH APTER 10 Reactions of Alcohols, Ethers, Epoxides, Amines, and Sulfur-Containing Compounds 458 CH APTER 11 Organometallic Compounds 508 CH APTER 12 Radicals 532 TU TO R IAL Drawing Curved Arrows in Radical Systems 563 CH APTER 13 Mass Spectrometry; Infrared Spectroscopy; UV/Vis Spectroscopy 567 CH APTER 14 NMR Spectroscopy 620 CHAPTER 15 Reactions of Carboxylic Acids and Carboxylic Acid Derivatives 686 iv     v C HA P TE R 1 6 Reactions of Aldehydes and Ketones More Reactions of Carboxylic Acid Derivatives 739 C HA P TE R 1 7 Reactions at the a-Carbon 801 TUTO R I A L Synthesis and Retrosynthetic Analysis 854 C HA P TE R 1 8 Reactions of Benzene and Substituted Benzenes 868 C HA P TE R 1 9 More About Amines Reactions of Heterocyclic Compounds 924 C HA P TE R 2 0 The Organic Chemistry of Carbohydrates 950 C HA P TE R 2 1 Amino Acids, Peptides, and Proteins 986 C HA P TE R 2 2 Catalysis in Organic Reactions and in Enzymatic Reactions 1030 C HA P TE R 2 3 The Organic Chemistry of the Coenzymes, Compounds Derived from Vitamins 1063 C HA P TE R 2 4 The Organic Chemistry of the Metabolic Pathways 1099 C HA P TE R 2 5 The Organic Chemistry of Lipids 1127 C HA P TE R 2 6 The Chemistry of the Nucleic Acids 1155 C HA P TE R 2 7 Synthetic Polymers 1182 C HA P TE R 2 8 Pericyclic Reactions 1212 A P P E ND I C E S I  pKa Values A-1 II  Kinetics A-3 III  Summary of Methods Used to Synthesize a Particular Functional Group A-8 IV  Summary of Methods Employed to Form Carbon–Carbon Bonds A-11 V  Spectroscopy Tables A-12 VI  Physical Properties of Organic Compounds A-18 VII  Answers to Selected Problems ANS-1 Glossary G-1 Photo Credits C-1 Index I-1 Complete List of In-Chapter Connection Features Medical Connections Naturally Occurring Alkyl Halides That Defend Against Predators (9.5) Biological Dehydrations (10.4) Fosamax Prevents Bones from Being Nibbled Away (2.8) Alkaloids (10.9) Aspirin Must Be in its Basic Form to be Physiologically Active (2.10) Dalmatians: Do Not Fool with Mother Nature (15.11) Blood: A Buffered Solution (2.11) A Semisynthetic Penicillin (15.12) Drugs Bind to Their Receptors (3.9) Preserving Biological Specimens (16.9) Cholesterol and Heart Disease (3.16) A Biological Friedel-Crafts Alkylation (18.7) How High Cholesterol is Treated Clinically (3.16) A Toxic Disaccharide (20.15) The Enantiomers of Thalidomide (4.17) Controlling Fleas (20.16) Synthetic Alkynes Are Used to Treat Parkinson’s Disease (7.0) Primary Structure and Taxonomic Relationship (21.12) Synthetic Alkynes Are Used for Birth Control (7.1) Competitive Inhibitors (23.7) The Inability to Perform an SN2 Reaction Causes a Severe ­ Whales and Echolocation (25.3) Clinical Disorder (10.3) Snake Venom (25.5) Treating Alcoholism with Antabuse (10.5) Cyclic AMP (26.1) Methanol Poisoning (10.5) There Are More Than Four Bases in DNA (26.7) Anesthetics (10.6) Alkylating Agents as Cancer Drugs (10.11) S-Adenosylmethionine: A Natural Antidepressant (10.12) Chemical Connections Artificial Blood (12.12) Natural versus Synthetic Organic Compounds (1.0) Nature’s Sleeping Pill (15.1) Diamond, Graphite, Graphene, and Fullerenes: Substances that Contain Penicillin and Drug Resistance (15.12) Only Carbon Atoms (1.8) Dissolving Sutures (15.13) Water—A Unique Compound (1.12) Cancer Chemotherapy (16.17) Acid Rain (2.2) Breast Cancer and Aromatase Inhibitors (17.12) Derivation of the Henderson-Hasselbalch Equation (2.10) Thyroxine (18.3) Bad-Smelling Compounds (3.7) A New Cancer-Fighting Drug (18.20) Von Baeyer, Barbituric Acid, and Blue Jeans (3.12) Atropine (19.2) Starch and Cellulose—Axial and Equatorial (3.14) Porphyrin, Bilirubin, and Jaundice (19.7) Cis-Trans Interconversion in Vision (4.1) Measuring the Blood Glucose Levels in Diabetes (20.8) The Difference between ∆G‡ and Ea (5.11) Galactosemia (20.15) Calculating Kinetic Parameters (End of Ch 05) Why the Dentist is Right (20.16) Borane and Diborane (6.8) Resistance to Antibiotics (20.17) Cyclic Alkenes (6.13) Heparin–A Natural Anticoagulant (20.17) Chiral Catalysts (6.15) Amino Acids and Disease (21.2) Sodium Amide and Sodium in Ammonia (7.10) Diabetes (21.8) Buckyballs (8.18) Diseases Caused by a Misfolded Protein (21.15) Why Are Living Organisms Composed of Carbon Instead of Silicon? (9.2) How Tamiflu Works (22.11) Solvation Effects (9.14) Assessing the Damage After a Heart Attack (23.5) The Lucas Test (10.1) Cancer Drugs and Side Effects (23.7) Crown Ethers—Another Example of Molecular Recognition (10.7) Anticoagulants (23.8) Crown Ethers Can be Used to Catalyze SN2 Reactions (10.7) Phenylketonuria (PKU): An Inborn Error of Metabolism (24.8) Eradicating Termites (10.12) Alcaptonuria (24.8) Cyclopropane (12.9) Multiple Sclerosis and the Myelin Sheath (25.5) What Makes Blueberries Blue and Strawberries Red? (13.22) How Statins Lower Cholesterol Levels (25.8) Nerve Impulses, Paralysis, and Insecticides (15.19) One Drug—Two Effects (25.10) Enzyme-Catalyzed Carbonyl Additions (16.4) Sickle Cell Anemia (26.9) Carbohydrates (16.9) Antibiotics That Act by Inhibiting Translation (26.9) b-Carotene (16.13) Antibiotics Act by a Common Mechanism (26.10) Synthesizing Organic Compounds (16.14) Health Concerns: Bisphenol A and Phthalates (27.11) Enzyme-Catalyzed Cis-Trans Interconversion (16.16) Incipient Primary Carbocations (18.7) Biological Connections Hair: Straight or Curly? (21.8) Right-Handed and Left-Handed Helices (21.14) Poisonous Amines (2.3) b-Peptides: An Attempt to Improve on Nature (21.14) Cell Membranes (3.10) Why Did Nature Choose Phosphates? (24.1) How a Banana Slug Knows What to Eat (7.2) Protein Prenylation (25.8) Electron Delocalization Affects the Three-Dimensional Shape of Bioluminescence (28.6) Proteins (8.4) vi    vii Pharmaceutical Connections Basal Metabolic Rate (24.10) Omega Fatty Acids (25.1) Chiral Drugs (4.18) Olestra: Nonfat with Flavor (25.3) Why Are Drugs so Expensive? (7.0) Melamine Poisoning (27.12) Lead Compounds for the Development of Drugs (10.9) The Sunshine Vitamin (28.6) Aspirin, NSAIDs, and COX-2 Inhibitors (15.9) Animals, Birds, Fish—And Vitamin D (28.6) Penicillins in Clinical Use (15.12) Serendipity in Drug Development (16.8) Industrial Connections Semisynthetic Drugs (16.14) Drug Safety (18.19) How is the Octane Number of Gasoline Determined? (3.2) Searching for Drugs: An Antihistamine, a Nonsedating Antihistamine, Organic Compounds That Conduct Electricity (8.7) and a Drug for Ulcers (19.7) Synthetic Polymers (15.13) A Peptide Antibiotic (21.2) The Synthesis of Aspirin (17.7) Natural Products That Modify DNA (26.6) Teflon: An Accidental Discovery (27.3) Using Genetic Engineering to Treat the Ebola Virus (26.13) Designing a Polymer (27.11) Nanocontainers (27.9) Environmental Connections Historical Connections Pheromones (5.0) Kekule’s Dream (8.1) Which are More Harmful: Natural Pesticides or Synthetic Mustard Gas–A Chemical Warfare Agent (10.11) Pesticides? (6.16) Grubbs, Schrock, Suzuki, and Heck Receive Green Chemistry: Aiming for Sustainability (7.12) the Nobel Prize (11.5) The Birth of the Environmental Movement (9.0) The Nobel Prize (11.5) Environmental Adaptation (9.14) Why Radicals No Longer Have to Be Called Free Radicals (12.2) Benzo[a]pyrene and Cancer (10.8) Nikola Tesla (1856–1943) (14.1) Chimney Sweeps and Cancer (10.8) The Discovery of Penicillin (15.12) Resisting Herbicides (26.13) Discovery of the First Antibiotic (18.19) Recycling Symbols (27.3) Vitamin C (20.17) Vitamin B1 (23.0) General Connections Niacin Deficiency (23.1) The First Antibiotics (23.7) A Few Words About Curved Arrows (5.5) The Structure of DNA: Watson, Crick, Franklin, and Wilkins (26.1) Grain Alcohol and Wood Alcohol (10.1) Influenza Pandemics (26.11) Blood Alcohol Concentration (10.5) Natural Gas and Petroleum (12.1) Fossil Fuels: A Problematic Energy Source (12.1) Nutritional Connections Mass Spectrometry in Forensics (13.8) Trans Fats (5.9) The Originator of Hooke’s Law (13.13) Decaffeinated Coffee and the Cancer Scare (12.11) Ultraviolet Light and Sunscreens (13.19) Food Preservatives (12.11) Structural Databases (14.24) Is Chocolate a Health Food? (12.11) What Drug-Enforcement Dogs Are Really Detecting (15.16) Nitrosamines and Cancer (18.20) Butanedione: An Unpleasant Compound (16.1) Lactose Intolerance (20.15) Measuring Toxicity (18.0) Acceptable Daily Intake (20.19) The Toxicity of Benzene (18.1) Proteins and Nutrition (21.1) Glucose/Dextrose (20.9) Too Much Broccoli (23.8) Water Softeners: Examples of Cation-Exchange Differences in Metabolism (24.0) Chromatography (21.5) Fats Versus Carbohydrates as a Source of Energy (24.6) Curing a Hangover with Vitamin B1 (23.3) Contents PART An Introduction to the Study of Organic Chemistry 1 ONE 1 Remembering General Chemistry: Electronic Structure and Bonding CHEMICAL CONNECTION: Natural versus Synthetic Organic Compounds 3 2 1.1 The Structure of an Atom 4 1.2 How the Electrons in an Atom are Distributed 5 1.3 Covalent Bonds 7 1.4 How the Structure of a Compound is Represented 13 P R O B L E M - S O LV I N G S T R AT E G Y 15 1.5 Atomic Orbitals 19 1.6 An Introduction to Molecular Orbital Theory 21 1.7 How Single Bonds are Formed in Organic Compounds 25 1.8 How a Double Bond is Formed: The Bonds in Ethene 29 CHEMICAL CONNECTION: Diamond, Graphite, Graphene, and Fullerenes: Substances that Contain Only Carbon Atoms 31 1.9 How a Triple Bond is Formed: The Bonds in Ethyne 31 1.10 The Bonds in the Methyl Cation, the Methyl Radical, and the Methyl Anion 33 1.11 The Bonds in Ammonia and in the Ammonium Ion 35 1.12 The Bonds in Water 36 CHEMICAL CONNECTION: Water—A Unique Compound 37 1.13 The Bond in a Hydrogen Halide 38 1.14 Hybridization and Molecular Geometry 39 P R O B L E M - S O LV I N G S T R AT E G Y 39 1.15 Summary: Hybridization, Bond Lengths, Bond Strengths, and Bond Angles 40 P R O B L E M - S O LV I N G S T R AT E G Y 44 1.16 Dipole Moments of Molecules 44 ESSENTIAL CONCEPTS PROBLEMS 2 46 47 Acids and Bases: Central to Understanding Organic Chemistry 50 2.1 An Introduction to Acids and Bases  50 2.2 pKa and pH 52 P R O B L E M - S O LV I N G S T R AT E G Y 54 CHEMICAL CONNECTION: Acid Rain 54 2.3 Organic Acids and Bases 55 BIOLOGICAL CONNECTION: Poisonous Amines 56 P R O B L E M - S O LV I N G S T R AT E G Y 58 2.4 How to Predict the Outcome of an Acid-Base Reaction 58 2.5 How to Determine the Position of Equilibrium 59 2.6 How the Structure of an Acid Affects its pKa Value 60 for Organic Chemistry 2.7 How Substituents Affect the Strength of an Acid 64 MasteringChemistry tutorials guide you through P R O B L E M - S O LV I N G S T R AT E G Y 64 the toughest topics in chemistry with self-paced tutorials that provide individualized coaching. These 2.8 An Introduction to Delocalized Electrons 66 assignable, in-depth tutorials are designed to MEDICAL CONNECTION: Fosamax Prevents Bones from Being Nibbled Away 67 coach you with hints and feedback specific to your P R O B L E M - S O LV I N G S T R AT E G Y 68 individual misconceptions. For additional practice on Acids and Bases, go to MasteringChemistry, 2.9 A Summary of the Factors that Determine Acid Strength 69 where the following tutorials are available: 2.10 How pH Affects the Structure of an Organic Compound 70 P R O B L E M - S O LV I N G S T R AT E G Y 71 Acids and Bases: Definitions  Acids and Bases: Factors That Influence Acid CHEMICAL CONNECTION: Derivation of the Henderson-Hasselbalch Equation 72 Strength MEDICAL CONNECTION: Aspirin Must Be in its Basic Form to be Physiologically Active 74  Acids and Bases: Base Strength and the Effect 2.11 Buffer Solutions 74 of pH on Structure MEDICAL CONNECTION: Blood: A Buffered Solution 75  Acids and Bases: Predicting the Position of 2.12 Lewis Acids and Bases 76 Equilibrium ESSENTIAL CONCEPTS 77 PROBLEMS 77 viii TUTORIAL Acids and Bases 80 3 An Introduction to Organic Compounds: Nomenclature, Physical Properties, and Structure 88 3.1 Alkyl Groups 92 3.2 The Nomenclature of Alkanes 95 INDUSTRIAL CONNECTION: How is the Octane Number of Gasoline Determined? 98 3.3 The Nomenclature of Cycloalkanes 99 P R O B L E M - S O LV I N G S T R AT E G Y 101 3.4 The Nomenclature of Alkyl Halides 101 3.5 The Nomenclature of Ethers 103 3.6 The Nomenclature of Alcohols 104 3.7 The Nomenclature of Amines 106 CHEMICAL CONNECTION: Bad-Smelling Compounds 109 3.8 The Structures of Alkyl Halides, Alcohols, Ethers, and Amines 109 3.9 Noncovalent Interactions 110 P R O B L E M - S O LV I N G S T R AT E G Y 114 MEDICAL CONNECTION: Drugs Bind to Their Receptors 114 3.10 The Solubility of Organic Compounds 116 BIOLOGICAL CONNECTION: Cell Membranes 118 3.11 Rotation Occurs about Carbon–Carbon Single Bonds 118 3.12 Some Cycloalkanes Have Angle Strain 122 for Organic Chemistry CHEMICAL CONNECTION: Von Baeyer, Barbituric Acid, and Blue Jeans 123 Mastering Chemistry tutorials guide you P R O B L E M - S O LV I N G S T R AT E G Y 123 through the toughest topics in chemistry with 3.13 Conformers of Cyclohexane 124 self-paced tutorials that provide individualized coaching. These assignable, in-depth tutorials are 3.14 Conformers of Monosubstituted Cyclohexanes 127 designed to coach you with hints and feedback CHEMICAL CONNECTION: Starch and Cellulose—Axial and Equatorial 128 specific to your individual misconceptions. For 3.15 Conformers of Disubstituted Cyclohexanes 129 additional practice on Molecular Models, go to P R O B L E M - S O LV I N G S T R AT E G Y 130 MasteringChemistry where the following tutorials are available: P R O B L E M - S O LV I N G S T R AT E G Y 132 3.16 Fused Cyclohexane Rings 134 Basics of Model Building MEDICAL CONNECTION: Cholesterol and Heart Disease 134 Building and Recognizing Chiral Molecules MEDICAL CONNECTION: How High Cholesterol is Treated Clinically 135 Recognizing Chirality in Cyclic Molecules ESSENTIAL CONCEPTS 135 PROBLEMS 136 PART E lectrophilic Addition Reactions, Stereochemistry, TWO and Electron Delocalization 141 TUTORIAL Using Molecular Models 142 4 Using the E,Z system to name Isomers: The Arrangement of Atoms in Space 143 alkenes was moved to Chapter 4, so now it appears immediately after using cis and trans to distinguish 4.1 Cis–Trans Isomers Result from Restricted Rotation 145 alkene stereoisomers. CHEMICAL CONNECTION: Cis-Trans Interconversion in Vision 147 4.2 Using the E,Z System to Distinguish Isomers 147 P R O B L E M - S O LV I N G S T R AT E G Y 150 4.3 A Chiral Object Has a Nonsuperimposable Mirror Image 150 for Organic Chemistry 4.4 An Asymmetric Center is a Cause of Chirality in a Molecule 151 MasteringChemistry tutorials guide you 4.5 Isomers with One Asymmetric Center 152 through the toughest topics in chemistry with 4.6 Asymmetric Centers and Stereocenters 153 self-paced tutorials that provide individualized 4.7 How to Draw Enantiomers 153 coaching. These assignable, in-depth tutorials are designed to coach you with hints and feedback 4.8 Naming Enantiomers by the R,S System 154 specific to your individual misconceptions. P R O B L E M - S O LV I N G S T R AT E G Y 157 For additional practice on Interconverting Structural P R O B L E M - S O LV I N G S T R AT E G Y 158 Representations, go to MasteringChemistry where the following tutorials are available: 4.9 Chiral Compounds Are Optically Active 159 4.10 How Specific Rotation Is Measured 161 Interconverting Fischer Projections and 4.11 Enantiomeric Excess 163 Perspective Formulas 4.12 Compounds with More than One Asymmetric Center 164  Interconverting Perspective Formulas, Fischer 4.13 Stereoisomers of Cyclic Compounds 166 Projections, and Skeletal Structures P R O B L E M - S O LV I N G S T R AT E G Y 168 Interconverting Perspective Formulas, Fischer Projections, and Newman Projections 4.14 Meso Compounds Have Asymmetric Centers but Are Optically Inactive 169 P R O B L E M - S O LV I N G S T R AT E G Y 171 x 4.15 How to Name Isomers with More than One Asymmetric Center 172 P R O B L E M - S O LV I N G S T R AT E G Y 175 4.16 Nitrogen and Phosphorus Atoms Can Be Asymmetric Centers 177 4.17 Receptors 178 MEDICAL CONNECTION: The Enantiomers of Thalidomide 179 4.18 How Enantiomers Can Be Separated 179 PHARMACEUTICAL CONNECTION: Chiral Drugs 180 ESSENTIAL CONCEPTS 181 PROBLEMS 181 TUTORIAL Interconverting Structural Representations 187 Catalytic hydrogenation and relative stabilities of alkenes were 5 Alkenes: Structure, Nomenclature, and an Introduction to Reactivity Thermodynamics and Kinetics 190 moved from Chapter 6 to Chapter 5 ENVIRONMENTAL CONNECTION: Pheromones 191 (thermodynamics), so they can be used to illustrate how ΔH° values 5.1 Molecular Formulas and the Degree of Unsaturation 191 can be used to determine relative 5.2 The Nomenclature of Alkenes 192 stabilities. 5.3 The Structure of Alkenes 195 P R O B L E M - S O LV I N G S T R AT E G Y 196 5.4 How An Organic Compound Reacts Depends on Its Functional Group 197 5.5 How Alkenes React Curved Arrows Show the Flow of Electrons 198 GENERAL CONNECTION: A Few Words About Curved Arrows 200 5.6 Thermodynamics: How Much Product is Formed? 202 for Organic Chemistry 5.7 Increasing the Amount of Product Formed in a Reaction 205 MasteringChemistry tutorials guide you through 5.8 Calculating ∆H ° Values 206 the toughest topics in chemistry with self-paced 5.9 Using ∆H ° Values to Determine the Relative Stabilities of Alkenes 207 tutorials that provide individualized coaching. These assignable, in-depth tutorials are designed P R O B L E M - S O LV I N G S T R AT E G Y 208 to coach you with hints and feedback specific NUTRITIONAL CONNECTION: Trans Fats 211 to your individual misconceptions. For additional 5.10 Kinetics: How Fast is the Product Formed? 211 practice on Drawing Curved Arrows: Pushing 5.11 The Rate of a Chemical Reaction 213 Electrons, go to MasteringChemistry where the following tutorials are available: CHEMICAL CONNECTION: The Difference between ∆G ‡ and Ea 215  An Exercise in Drawing Curved Arrows: Pushing 5.12 A Reaction Coordinate Diagram Describes the Energy Changes That Take Place During Electrons a ­Reaction 215  An Exercise in Drawing Curved Arrows: 5.13 Catalysis 218 Predicting Electron Movement 5.14 Catalysis by Enzymes 219  An Exercise in Drawing Curved Arrows: ESSENTIAL CONCEPTS 220 PROBLEMS 221 Interpreting Electron Movement CHEMICAL CONNECTION: Calculating Kinetic Parameters 224 TUTORIAL Drawing Curved Arrows 225 All the reactions in Chapter 6 follow the same mechanism the first step is 6 The Reactions of Alkenes The Stereochemistry of Addition Reactions 235 always addition of the electrophile 6.1 The Addition of a Hydrogen Halide to an Alkene 236 to the sp2 carbon bonded to the most 6.2 Carbocation Stability Depends on the Number of Alkyl Groups Attached to the Positively hydrogens. Charged Carbon 237 6.3 What Does the Structure of the Transition State Look Like? 239 6.4 Electrophilic Addition Reactions Are Regioselective 241 P R O B L E M - S O LV I N G S T R AT E G Y 243 6.5 The Addition of Water to an Alkene 245 6.6 The Addition of an Alcohol to an Alkene 246 6.7 A Carbocation Will Rearrange if It Can Form a More Stable Carbocation 248 6.8 The Addition of Borane to an Alkene: Hydroboration–Oxidation 250 CHEMICAL CONNECTION: Borane and Diborane 251 6.9 The Addition of a Halogen to an Alkene 254 P R O B L E M - S O LV I N G S T R AT E G Y 257 6.10 The Addition of a Peroxyacid to an Alkene 257 6.11 The Addition of Ozone to an Alkene: Ozonolysis 259 P R O B L E M - S O LV I N G S T R AT E G Y 261 6.12 Regioselective, Stereoselective, And Stereospecific Reactions 263 6.13 The Stereochemistry of Electrophilic Addition Reactions 264 CHEMICAL CONNECTION: Cyclic Alkenes 269 P R O B L E M - S O LV I N G S T R AT E G Y 274 6.14 The Stereochemistry of Enzyme-Catalyzed Reactions 276  xi   6.15 Enantiomers Can Be Distinguished by Biological Molecules 277 CHEMICAL CONNECTION: Chiral Catalysts 278 6.16 Reactions and Synthesis 278 ENVIRONMENTAL CONNECTION: Which are More Harmful: Natural Pesticides or Synthetic ­Pesticides? 280 ESSENTIAL CONCEPTS 280 SUMMARY OF REACTIONS 281 PROBLEMS 282 7 The Reactions of Alkynes An Introduction to Multistep Synthesis 288 MEDICAL CONNECTION: Synthetic Alkynes Are Used to Treat Parkinson’s Disease 289 PHARMACEUTICAL CONNECTION: Why Are Drugs so Expensive? 290 7.1 The Nomenclature of Alkynes 290 MEDICAL CONNECTION: Synthetic Alkynes Are Used for Birth Control 291 7.2 How to Name a Compound That Has More than One Functional Group 292 7.3 The Structure of Alkynes 293 BIOLOGICAL CONNECTION: How a Banana Slug Knows What to Eat 293 7.4 The Physical Properties of Unsaturated Hydrocarbons 294 7.5 The Reactivity of Alkynes 295 Chapter 8 starts by discussing the 7.6 The Addition of Hydrogen Halides and the Addition of Halogens to an Alkyne 296 structure of benzene because it is 7.7 The Addition of Water to an Alkyne 299 the ideal compound to use to explain delocalized electrons. This chapter 7.8 The Addition of Borane to an Alkyne: Hydroboration–Oxidation 301 also includes a discussion of 7.9 The Addition of Hydrogen to an Alkyne 302 aromaticity, so a short introduction 7.10 A Hydrogen Bonded to an sp Carbon Is “Acidic” 304 to electrophilic aromatic substitution CHEMICAL CONNECTION: Sodium Amide and Sodium in Ammonia 305 reactions is now included. This allows students to see how P R O B L E M - S O LV I N G S T R AT E G Y 305 aromaticity causes benzene to 7.11 Synthesis Using Acetylide Ions 306 undergo electrophilic substitution 7.12 DESIGNING A SYNTHESIS I: An Introduction to Multistep Synthesis 307 rather than electrophilic addition— ENVIRONMENTAL CONNECTION: Green Chemistry: Aiming for Sustainability 312 the reactions they have just finished studying. ESSENTIAL CONCEPTS 312 SUMMARY OF REACTIONS 313 PROBLEMS 314 8 Delocalized Electrons: Their Effect on Stability, pKa, and the Products of a Reaction Aromaticity and Electronic Effects: An Introduction to the Traditionally, electronic effects are taught so students can understand the directing effects of substituents Reactions of Benzene 318 on benzene rings. Now that most of the chemistry of benzene follows 8.1 Delocalized Electrons Explain Benzene’s Structure 319 carbonyl chemistry, students HISTORICAL CONNECTION: Kekule’s Dream 321 need to know about electronic 8.2 The Bonding in Benzene 321 effects before they get to benzene 8.3 Resonance Contributors and the Resonance Hybrid 322 chemistry (so they are better 8.4 How to Draw Resonance Contributors 323 prepared for spectroscopy and carbonyl chemistry). Therefore, BIOLOGICAL CONNECTION: Electron Delocalization Affects the Three-Dimensional Shape of electronic effects are now discussed ­Proteins 326 in Chapter 8 and used to teach 8.5 The Predicted Stabilities of Resonance Contributors 326 students how substituents affect P R O B L E M - S O LV I N G S T R AT E G Y 328 the pKa values of phenols, benzoic acids, and anilinium ions. Electronic 8.6 Delocalization Energy is the Additional Stability Delocalized Electrons effects are then reviewed in the Give to a Compound 329 chapter on benzene. 8.7 Delocalized Electrons Increase Stability 330 INDUSTRIAL CONNECTION: Organic Compounds That Conduct Electricity 333 8.8 A Molecular Orbital Description of Stability 335 8.9 Delocalized Electrons Affect pKa Values 339 for Organic Chemistry P R O B L E M - S O LV I N G S T R AT E G Y 342 MasteringChemistry tutorials guide you through the 8.10 Electronic Effects 342 toughest topics in ­chemistry with self-paced tutorials 8.11 Delocalized Electrons Can Affect the Product of a Reaction 346 that provide individualized coaching. These assign- 8.12 Reactions of Dienes 347 able, in-depth tutorials are designed to coach you 8.13 Thermodynamic Versus Kinetic Control 350 with hints and feedback specific to your individual misconceptions. For additional practice on Drawing 8.14 The Diels–Alder Reaction is a 1,4-Addition Reaction 355 Resonance Contributors, go to MasteringChemistry 8.15 Retrosynthetic Analysis of the Diels–Alder Reaction 361 where the following tutorials are available: 8.16 Benzene is an Aromatic Compound 362  Drawing Resonance Contributors: Moving p 8.17 The Two Criteria for Aromaticity 363 Electrons 8.18 Applying the Criteria for Aromaticity 364  Drawing Resonance Contributors: Predicting CHEMICAL CONNECTION: Buckyballs 365 Aromaticity P R O B L E M - S O LV I N G S T R AT E G Y 366  Drawing Resonance Contributors: Substituted Benzene Rings 8.19 A Molecular Orbital Description of Aromaticity 367 xii 8.20 Aromatic Heterocyclic Compounds 368 8.21 How Benzene Reacts 370 8.22 Organizing What We Know About the Reactions of Organic Compounds (Group I) 372 ESSENTIAL CONCEPTS 373 SUMMARY OF REACTIONS 374 PROBLEMS 375 TUTORIAL Drawing Resonance Contributors 382 PART Substitution and Elimination Reactions 390 THREE The two chapters in the previous edition on substitution and 9 Substitution and Elimination Reactions of Alkyl Halides 391 elimination reactions of alkenes ENVIRONMENTAL CONNECTION: The Birth of the Environmental Movement 392 have been combined into one 9.1 The SN2 Reaction 393 chapter. The recent compelling 9.2 Factors That Affect SN2 Reactions 398 evidence showing that secondary CHEMICAL CONNECTION: Why Are Living Organisms Composed of Carbon Instead of ­Silicon? 405 alkyl halides do not undergo SN1 9.3 The SN1 Reaction 406 solvolysis reactions has allowed this material to be greatly simplified, so 9.4 Factors That Affect SN1 Reactions 409 now it fits nicely into one chapter. 9.5 Competition Between SN2 and SN1 Reactions 410 P R O B L E M - S O LV I N G S T R AT E G Y 411 BIOLOGICAL CONNECTION: Naturally Occurring Alkyl Halides That Defend Against ­Predators 412 9.6 Elimination Reactions of Alkyl Halides 412 9.7 The E2 Reaction 413 9.8 The E1 Reaction 419 P R O B L E M - S O LV I N G S T R AT E G Y 421 9.9 Competition Between E2 and E1 Reactions 422 9.10 E2 and E1 Reactions are Stereoselective 423 P R O B L E M - S O LV I N G S T R AT E G Y 425 9.11 Elimination from Substituted Cyclohexanes 427 9.12 Predicting the Products of the Reaction of an Alkyl Halide with a Nucleophile/Base 429 9.13 Benzylic Halides, Allylic Halides, Vinylic Halides, and Aryl Halides 433 P R O B L E M - S O LV I N G S T R AT E G Y 434 P R O B L E M - S O LV I N G S T R AT E G Y 437 9.14 Solvent Effects 438 CHEMICAL CONNECTION: Solvation Effects 438 ENVIRONMENTAL CONNECTION: Environmental Adaptation 441 9.15 Substitution and Elimination Reactions in Synthesis 442 9.16 Intermolecular Versus Intramolecular Reactions 444 P R O B L E M - S O LV I N G S T R AT E G Y 446 9.17 DESIGNING A SYNTHESIS II: Approaching the Problem 446 ESSENTIAL CONCEPTS 449 SUMMARY OF REACTIONS 450 PROBLEMS 451 10  eactions of Alcohols, Ethers, Epoxides, Amines, and R Sulfur-Containing Compounds 458 10.1 Nucleophilic Substitution Reactions of Alcohols: Forming Alkyl Halides 459 CHEMICAL CONNECTION: The Lucas Test 461 GENERAL CONNECTION: Grain Alcohol and Wood Alcohol 462 10.2 Other Methods Used to Convert Alcohols into Alkyl Halides 463 10.3 Converting an Alcohol Into a Sulfonate Ester 465 MEDICAL CONNECTION: The Inability to Perform an SN2 Reaction Causes a ­Severe ­Clinical ­Disorder 467 10.4 Elimination Reactions of Alcohols: Dehydration 468 P R O B L E M - S O LV I N G S T R AT E G Y 471 BIOLOGICAL CONNECTION: Biological Dehydrations 473 10.5 Oxidation of Alcohols 474 GENERAL CONNECTION: Blood Alcohol Concentration 476 MEDICAL CONNECTION: Treating Alcoholism with Antabuse 476 MEDICAL CONNECTION: Methanol Poisoning 477  xiii   10.6 Nucleophilic Substitution Reactions of Ethers 477 MEDICAL CONNECTION: Anesthetics 478 10.7 Nucleophilic Substitution Reactions of Epoxides 480 CHEMICAL CONNECTION: Crown Ethers—Another Example of Molecular Recognition 484 CHEMICAL CONNECTION: Crown Ethers Can be Used to Catalyze SN2 Reactions 485 10.8 Arene Oxides 485 ENVIRONMENTAL CONNECTION: Benzo[a]pyrene and Cancer 488 ENVIRONMENTAL CONNECTION: Chimney Sweeps and Cancer 489 10.9 Amines Do Not Undergo Substitution or Elimination Reactions 490 BIOLOGICAL CONNECTION: Alkaloids 491 PHARMACEUTICAL CONNECTION: Lead Compounds for the Development of Drugs 491 10.10 Quaternary Ammonium Hydroxides Undergo Elimination Reactions 492 10.11 Thiols, Sulfides, and Sulfonium Ions 494 HISTORICAL CONNECTION: Mustard Gas–A Chemical Warfare Agent 495 MEDICAL CONNECTION: Alkylating Agents as Cancer Drugs 496 10.12 Methylating Agents Used by Chemists versus Those Used by Cells 496 CHEMICAL CONNECTION: Eradicating Termites 497 MEDICAL CONNECTION: S-Adenosylmethionine: A Natural Antidepressant 498 10.13 Organizing What We Know About the Reactions of Organic Compounds (Group II) 499 ESSENTIAL CONCEPTS 500 SUMMARY OF REACTIONS 501 PROBLEMS 503 11 Organometallic Compounds 508 The discussion of palladium- catalyzed coupling reactions has 11.1 Organolithium and Organomagnesium Compounds 509 been expanded, and the cyclic 11.2 Transmetallation 511 catalytic mechanisms are shown. 11.3 Organocuprates 512 11.4 Palladium-Catalyzed Coupling Reactions 515 P R O B L E M - S O LV I N G S T R AT E G Y 521 11.5 Alkene Metathesis 522 HISTORICAL CONNECTION: Grubbs, Schrock, Suzuki, and Heck Receive the Nobel Prize 526 HISTORICAL CONNECTION: The Nobel Prize 526 ESSENTIAL CONCEPTS 527 SUMMARY OF REACTIONS 527 PROBLEMS 528 12 Radicals 532 12.1 Alkanes are Unreactive Compounds 532 GENERAL CONNECTION: Natural Gas and Petroleum 533 GENERAL CONNECTION: Fossil Fuels: A Problematic Energy Source 533 12.2 The Chlorination and Bromination of Alkanes 534 HISTORICAL CONNECTION: Why Radicals No Longer Have to Be Called Free Radicals 536 12.3 Radical Stability Depends on the Number of Alkyl Groups Attached to the Carbon with the ­Unpaired Electron 536 12.4 The Distribution of Products Depends on Probability and Reactivity 537 12.5 The Reactivity–Selectivity Principle 539 P R O B L E M - S O LV I N G S T R AT E G Y 541 for Organic Chemistry 12.6 Formation of Explosive Peroxides 542 MasteringChemistry tutorials guide you through the toughest topics in chemistry with self-paced 12.7 The Addition of Radicals to an Alkene 543 tutorials that provide individualized coaching. These 12.8 The Stereochemistry of Radical Substitution and Radical Addition Reactions 546 assignable, in-depth tutorials are designed to 12.9 Radical Substitution of Allylic and Benzylic Hydrogens 547 coach you with hints and feedback specific to your CHEMICAL CONNECTION: Cyclopropane 550 individual misconceptions. For additional practice on 12.10 DESIGNING A SYNTHESIS III: More Practice with Multistep Synthesis 550 Drawing Curved Arrows in Radical Systems, go to MasteringChemistry where the following tutorials 12.11 Radical Reactions in Biological Systems 552 are available: NUTRITIONAL CONNECTION: Decaffeinated Coffee and the Cancer Scare 553  Curved Arrows in Radical Systems: Interpreting NUTRITIONAL CONNECTION: Food Preservatives 555 Curved Arrows NUTRITIONAL CONNECTION: Is Chocolate a Health Food? 556  Curved Arrows in Radical Systems: Drawing 12.12 Radicals and Stratospheric Ozone 556 Curved Arrows MEDICAL CONNECTION: Artificial Blood 558  Curved Arrows in Radical Systems: Drawing Resonance Contributors ESSENTIAL CONCEPTS 558 SUMMARY OF REACTIONS 559 PROBLEMS 559 TUTORIAL Drawing Curved Arrows in Radical Systems 563 xiv PART Identification of Organic Compounds 566 FOUR In addition to the more than 170 spectroscopy problems in Chapters 13 Mass Spectrometry; Infrared Spectroscopy; UV/Vis Spectroscopy 567 13 and 14, there are 60 additional 13.1 Mass Spectrometry 569 spectroscopy problems in the Study 13.2 The Mass Spectrum Fragmentation 570 Guide and Solutions Manual. 13.3 Using The m/z Value of the Molecular Ion to Calculate the Molecular Formula 572 P R O B L E M - S O LV I N G S T R AT E G Y 573 13.4 Isotopes in Mass Spectrometry 574 Chapters 13 and 14 are modular, so 13.5 High-Resolution Mass Spectrometry Can Reveal Molecular Formulas 575 they can be covered at any time. 13.6 The Fragmentation Patterns of Functional Groups 575 13.7 Other Ionization Methods 583 13.8 Gas Chromatography–Mass Spectrometry 583 GENERAL CONNECTION: Mass Spectrometry in Forensics 583 13.9 Spectroscopy and the Electromagnetic Spectrum 583 13.10 Infrared Spectroscopy 585 13.11 Characteristic Infrared Absorption Bands 588 13.12 The Intensity of Absorption Bands 589 13.13 The Position of Absorption Bands 590 GENERAL CONNECTION: The Originator of Hooke’s Law 590 13.14 The Position and Shape of an Absorption Band is Affected by Electron Delocalization and ­Hydrogen Bonding 591 P R O B L E M - S O LV I N G S T R AT E G Y 593 13.15 C ¬ H Absorption Bands 595 13.16 The Absence of Absorption Bands 598 13.17 Some Vibrations are Infrared Inactive 599 13.18 How to Interpret an Infrared Spectrum 600 13.19 Ultraviolet and Visible Spectroscopy 602 GENERAL CONNECTION: Ultraviolet Light and Sunscreens 603 13.20 The Beer–Lambert Law 604 13.21 The Effect of Conjugation on lmax 605 13.22 The Visible Spectrum and Color 606 CHEMICAL CONNECTION: What Makes Blueberries Blue and Strawberries Red? 607 13.23 Some Uses of UV/Vis Spectroscopy 608 ESSENTIAL CONCEPTS 610 PROBLEMS 611 14 NMR Spectroscopy 620 14.1 An Introduction to NMR Spectroscopy 620 HISTORICAL CONNECTION: Nikola Tesla (1856–1943) 622 14.2 Fourier Transform NMR 623 14.3 Shielding Causes Different Nuclei to Show Signals at Different Frequencies 623 14.4 The Number of Signals in an 1H NMR Spectrum 624 P R O B L E M - S O LV I N G S T R AT E G Y 625 14.5 The Chemical Shift Tells How Far the Signal Is from the Reference Signal 626 14.6 The Relative Positions of 1H NMR Signals 628 14.7 The Characteristic Values of Chemical Shifts 629 14.8 Diamagnetic Anisotropy 631 14.9 The Integration of NMR Signals Reveals the Relative Number of Protons Causing Each ­Signal 632 14.10 The Splitting of Signals Is Described by the N + 1 Rule 634 14.11 What Causes Splitting? 637 14.12 More Examples of 1H NMR Spectra 639 14.13 Coupling Constants Identify Coupled Protons 644 P R O B L E M - S O LV I N G S T R AT E G Y 646 14.14 Splitting Diagrams Explain the Multiplicity of a Signal 647 14.15 Enantiotopic and Diastereotopic Hydrogens 650 14.16 The Time Dependence of NMR Spectroscopy 652  xv   14.17 Protons Bonded to Oxygen and Nitrogen 652 14.18 The Use of Deuterium in 1H NMR Spectroscopy 654 14.19 The Resolution of 1H NMR Spectra 655 14.20 13C NMR Spectroscopy 657 P R O B L E M - S O LV I N G S T R AT E G Y 660 14.21 Dept 13C NMR Spectra 662 14.22 Two-Dimensional NMR Spectroscopy 662 14.23 NMR Used in Medicine is Called Magnetic Resonance Imaging 665 14.24 X-Ray Crystallography 666 GENERAL CONNECTION: Structural Databases 667 ESSENTIAL CONCEPTS 668 PROBLEMS 669 PART Carbonyl Compounds 685 The focus of the first chapter on carbonyl chemistry is all about FIVE how a tetrahedral intermediate partitions. If students understand this, then carbonyl chemistry 15 becomes pretty straightforward. I Reactions of Carboxylic Acids and Carboxylic Acid Derivatives 686 found that the lipid materil that had been put into this chapter in the last edition detracted from the main 15.1 The Nomenclature of Carboxylic Acids and Carboxylic Acid Derivatives 688 message of the chapter. Therefore, MEDICAL CONNECTION: Nature’s Sleeping Pill 691 the lipid material was removed and 15.2 The Structures of Carboxylic Acids and Carboxylic Acid Derivatives 692 put into a new chapter exclusively about lipids. 15.3 The Physical Properties of Carbonyl Compounds 693 15.4 How Carboxylic Acids and Carboxylic Acid Derivatives React 694 P R O B L E M - S O LV I N G S T R AT E G Y 696 15.5 The Relative Reactivities of Carboxylic Acids and Carboxylic Acid Derivatives 696 15.6 Reactions of Acyl Chlorides 698 15.7 Reactions of Esters 701 15.8 Acid-Catalyzed Ester Hydrolysis and Transesterification 702 15.9 Hydroxide-Ion-Promoted Ester Hydrolysis 706 PHARMACEUTICAL CONNECTION: Aspirin, NSAIDs, and COX-2 Inhibitors 707 15.10 Reactions of Carboxylic Acids 709 P R O B L E M - S O LV I N G S T R AT E G Y 710 15.11 Reactions of Amides 711 BIOLOGICAL CONNECTION: Dalmatians: Do Not Fool with Mother Nature 711 15.12 Acid-Catalyzed Amide Hydrolysis and Alcoholysis 712 HISTORICAL CONNECTION: The Discovery of Penicillin 713 MEDICAL CONNECTION: Penicillin and Drug Resistance 713 PHARMACEUTICAL CONNECTION: Penicillins in Clinical Use 714 BIOLOGICAL CONNECTION: A Semisynthetic Penicillin 714 15.13 Hydroxide-Ion-Promoted Hydrolysis of Amides 715 INDUSTRIAL CONNECTION: Synthetic Polymers 715 MEDICAL CONNECTION: Dissolving Sutures 716 15.14 Hydrolysis of an Imide: a Way to Synthesize a Primary Amine 716 15.15 Nitriles 717 15.16 Acid Anhydrides 719 GENERAL CONNECTION: What Drug-Enforcement Dogs Are Really Detecting 721 15.17 Dicarboxylic Acids 721 15.18 How Chemists Activate Carboxylic Acids 723 15.19 How Cells Activate Carboxylic Acids 724 CHEMICAL CONNECTION: Nerve Impulses, Paralysis, and Insecticides 727 ESSENTIAL CONCEPTS 728 SUMMARY OF REACTIONS 729 PROBLEMS 731 16 Reactions of Aldehydes and Ketones More Reactions of Carboxylic Acid Derivatives 739 16.1 The Nomenclature of Aldehydes and Ketones 740 GENERAL CONNECTION: Butanedione: An Unpleasant Compound 742 16.2 The Relative Reactivities of Carbonyl Compounds 743 16.3 How Aldehydes and Ketones React 744 xvi 16.4 Reactions of Carbonyl Compounds with Carbon Nucleophiles 745 CHEMICAL CONNECTION: Enzyme-Catalyzed Carbonyl Additions 747 P R O B L E M - S O LV I N G S T R AT E G Y 749 16.5 Reactions of Carbonyl Compounds with Hydride Ion 752 16.6 More About Reduction Reactions 757 16.7 Chemoselective Reactions 759 16.8 Reactions of Aldehydes and Ketones with Nitrogen Nucleophiles 760 PHARMACEUTICAL CONNECTION: Serendipity in Drug Development 765 16.9 Reactions of Aldehydes and Ketones with Oxygen Nucleophiles 766 BIOLOGICAL CONNECTION: Preserving Biological Specimens 768 CHEMICAL CONNECTION: Carbohydrates 770 P R O B L E M - S O LV I N G S T R AT E G Y 771 16.10 Protecting Groups 772 16.11 Reactions of Aldehydes and Ketones with Sulfur Nucleophiles 774 16.12 Reactions of Aldehydes and Ketones with a Peroxyacid 774 16.13 The Wittig Reaction Forms an Alkene 776 CHEMICAL CONNECTION: b-Carotene 777 16.14 DESIGNING A SYNTHESIS IV: Disconnections, Synthons, and Synthetic Equivalents 779 CHEMICAL CONNECTION: Synthesizing Organic Compounds 781 PHARMACEUTICAL CONNECTION: Semisynthetic Drugs 781 16.15 Nucleophilic Addition to a,b-Unsaturated Aldehydes and Ketones 781 16.16 Nucleophilic Addition to a,b-Unsaturated Carboxylic Acid Derivatives 785 CHEMICAL CONNECTION: Enzyme-Catalyzed Cis-Trans Interconversion 785 16.17 Conjugate Addition Reactions in Biological Systems 786 MEDICAL CONNECTION: Cancer Chemotherapy 786 ESSENTIAL CONCEPTS 787 SUMMARY OF REACTIONS 788 PROBLEMS 791 This chapter was reorganized and rewritten for ease of understanding. 17 Reactions at the A-Carbon 801 17.1 The Acidity of an a-Hydrogen 802 P R O B L E M - S O LV I N G S T R AT E G Y 804 17.2 Keto–Enol Tautomers 805 17.3 Keto–Enol Interconversion 806 17.4 Halogenation of the a-Carbon of Aldehydes and Ketones 807 17.5 Halogenation of the a-Carbon of Carboxylic Acids 809 17.6 Forming an Enolate Ion 810 17.7 Alkylating the a-Carbon 811 INDUSTRIAL CONNECTION: The Synthesis of Aspirin 813 P R O B L E M - S O LV I N G S T R AT E G Y 813 17.8 Alkylating and Acylating the a-Carbon Via an Enamine Intermediate 814 17.9 Alkylating the b-Carbon 815 17.10 An Aldol Addition Forms a b-Hydroxyaldehyde or a b-Hydroxyketone 817 17.11 The Dehydration of Aldol Addition Products Forms a,b-Unsaturated Aldehydes and ­Ketones 819 17.12 A Crossed Aldol Addition 821 MEDICAL CONNECTION: Breast Cancer and Aromatase Inhibitors 823 17.13 A Claisen Condensation Forms a b-Keto Ester 824 17.14 Other Crossed Condensations 827 17.15 Intramolecular Condensations and Intramolecular Aldol Additions 827 17.16 The Robinson Annulation 830 P R O B L E M - S O LV I N G S T R AT E G Y 830 17.17 CO2 Can be Removed from a Carboxylic Acid that has a Carbonyl Group at the 3-Position 831 17.18 The Malonic Ester Synthesis: A Way to Synthesize a Carboxylic Acid 833 17.19 The Acetoacetic Ester Synthesis: A Way to Synthesize a Methyl Ketone 834 17.20 DESIGNING A SYNTHESIS V: Making New Carbon–Carbon Bonds 836 17.21 Reactions at the a-Carbon in Living Systems 838 17.22 Organizing What We Know About the Reactions of Organic Compounds (Group III) 841 ESSENTIAL CONCEPTS 843 SUMMARY OF REACTIONS 844 PROBLEMS 846 TUTORIAL Synthesis and Retrosynthetic Analysis 854  xvii   PART Aromatic Compounds 867 SIX for Organic Chemistry 18 MasteringChemistry tutorials guide you through the Reactions of Benzene and Substituted Benzenes 868 toughest topics in chemistry with self-paced tutorials that provide individualized coaching. These assign- able, in-depth tutorials are designed to coach you GENERAL CONNECTION: Measuring Toxicity 869 with hints and feedback specific to your individual 18.1 The Nomenclature of Monosubstituted Benzenes 870 misconceptions. For additional practice on Synthesis and Retrosynthetic Analysis, go to MasteringChemis- GENERAL CONNECTION: The Toxicity of Benzene 871 try where the following tutorials are available: 18.2 The General Mechanism for Electrophilic Aromatic Substitution Reactions 871  Synthesis and Retrosynthetic Analysis: Changing 18.3 Halogenation of Benzene 872 the Functional Group MEDICAL CONNECTION: Thyroxine 874  Synthesis and Retrosynthetic Analysis: 18.4 Nitration of Benzene 874 Disconnections 18.5 Sulfonation of Benzene 875 Synthesis and Retrosynthetic Analysis: 18.6 Friedel–Crafts Acylation of Benzene 876 Synthesis of Carbonyl Compounds 18.7 Friedel–Crafts Alkylation of Benzene 877 CHEMICAL CONNECTION: Incipient Primary Carbocations 879 BIOLOGICAL CONNECTION: A Biological Friedel-Crafts Alkylation 879 18.8 Alkylation of Benzene by Acylation–Reduction 880 18.9 Using Coupling Reactions to Alkylate Benzene 881 18.10 How Some Substituents on a Benzene Ring Can Be Chemically Changed 882 18.11 The Nomenclature of Disubstituted and Polysubstituted Benzenes 884 18.12 The Effect of Substituents on Reactivity 886 18.13 The Effect of Substituents on Orientation 890 18.14 The Ortho–Para Ratio 894 18.15 Additional Considerations Regarding Substituent Effects 894 18.16 DESIGNING A SYNTHESIS VI: The Synthesis of Monosubstituted and Disubstituted Benzenes 896 18.17 The Synthesis of Trisubstituted Benzenes 898 18.18 Synthesizing Substituted Benzenes Using Arenediazonium Salts 900 18.19 Azobenzenes 903 HISTORICAL CONNECTION: Discovery of the First Antibiotic 904 PHARMACEUTICAL CONNECTION: Drug Safety 904 18.20 The Mechanism for the Formation of a Diazonium Ion 905 MEDICAL CONNECTION: A New Cancer-Fighting Drug 905 NUTRITIONAL CONNECTION: Nitrosamines and Cancer 906 18.21 Nucleophilic Aromatic Substitution 907 18.22 DESIGNING A SYNTHESIS VII: The Synthesis of Cyclic Compounds 909 ESSENTIAL CONCEPTS 910 SUMMARY OF REACTIONS 911 PROBLEMS 913 19 More About Amines Reactions of Heterocyclic Compounds 924 19.1 More About Nomenclature 925 19.2 More About the Acid–Base Properties of Amines 926 MEDICAL CONNECTION: Atropine 927 19.3 Amines React as Bases and as Nucleophiles 927 19.4 Synthesis of Amines 929 19.5 Aromatic Five-Membered-Ring Heterocycles 929 P R O B L E M - S O LV I N G S T R AT E G Y 931 19.6 Aromatic Six-Membered-Ring Heterocycles 934 19.7 Some Heterocyclic Amines Have Important Roles in Nature 939 PHARMACEUTICAL CONNECTION: Searching for Drugs: An Antihistamine, a Nonsedating ­Antihistamine, and a Drug for Ulcers 940 MEDICAL CONNECTION: Porphyrin, Bilirubin, and Jaundice 943 19.8 Organizing What We Know About the Reactions of Organic Compounds (Group IV) 943 ESSENTIAL CONCEPTS 944 SUMMARY OF REACTIONS 945 PROBLEMS 946 xviii PART Bioorganic Compounds 949 SEVEN 20 The Organic Chemistry of Carbohydrates 950 20.1 Classifying Carbohydrates 951 20.2 The d and l Notation 952 20.3 The Configurations of Aldoses 953 20.4 The Configurations of Ketoses 955 20.5 The Reactions of Monosaccharides in Basic Solutions 956 20.6 Oxidation–Reduction Reactions of Monosaccharides 957 20.7 Lengthening the Chain: The Kiliani–Fischer Synthesis 958 20.8 Shortening the Chain: The Wohl Degradation 959 MEDICAL CONNECTION: Measuring the Blood Glucose Levels in Diabetes 960 20.9 The Stereochemistry of Glucose: The Fischer Proof 960 GENERAL CONNECTION: Glucose/Dextrose 962 20.10 Monosaccharides Form Cyclic Hemiacetals 962 20.11 Glucose is the Most Stable Aldohexose 965 20.12 Formation of Glycosides 967 20.13 The Anomeric Effect 968 20.14 Reducing and Nonreducing Sugars 969 20.15 Disaccharides 969 NUTRITIONAL CONNECTION: Lactose Intolerance 971 MEDICAL CONNECTION: Galactosemia 971 BIOLOGICAL CONNECTION: A Toxic Disaccharide 972 20.16 Polysaccharides 973 MEDICAL CONNECTION: Why the Dentist is Right 974 BIOLOGICAL CONNECTION: Controlling Fleas 975 20.17 Some Naturally Occurring Compounds Derived from Carbohydrates 976 MEDICAL CONNECTION: Resistance to Antibiotics 976 MEDICAL CONNECTION: Heparin–A Natural Anticoagulant 977 HISTORICAL CONNECTION: Vitamin C 978 20.18 Carbohydrates on Cell Surfaces 978 20.19 Artificial Sweeteners 979 NUTRITIONAL CONNECTION: Acceptable Daily Intake 981 ESSENTIAL CONCEPTS 981 SUMMARY OF REACTIONS 982 PROBLEMS 983 New art adds clarity. 21 Amino Acids, Peptides, and Proteins 986 21.1 The Nomenclature of Amino Acids 987 NUTRITIONAL CONNECTION: Proteins and Nutrition 991 21.2 The Configuration of Amino Acids 991 MEDICAL CONNECTION: Amino Acids and Disease 992 PHARMACEUTICAL CONNECTION: A Peptide Antibiotic 992 21.3 Acid–Base Properties of Amino Acids 993 21.4 The Isoelectric Point 995 21.5 Separating Amino Acids 996 GENERAL CONNECTION: Water Softeners: Examples of Cation-Exchange Chromatography 1000 21.6 Synthesis of Amino Acids 1000 21.7 Resolution of Racemic Mixtures of Amino Acids 1002 21.8 Peptide Bonds and Disulfide Bonds 1003 MEDICAL CONNECTION: Diabetes 1006 CHEMICAL CONNECTION: Hair: Straight or Curly? 1006 21.9 Some Interesting Peptides 1006 21.10 The Strategy of Peptide Bond Synthesis: N-Protection and C-Activation 1007 21.11 Automated Peptide Synthesis 1010 21.12 An Introduction to Protein Structure 1013 BIOLOGICAL CONNECTION: Primary Structure and Taxonomic Relationship 1013 21.13 How to Determine the Primary Structure of a Polypeptide or a Protein 1013 P R O B L E M - S O LV I N G S T R AT E G Y 1015    xix 21.14 Secondary Structure 1019 CHEMICAL CONNECTION: Right-Handed and Left-Handed Helices 1020 CHEMICAL CONNECTION: b-Peptides: An Attempt to Improve on Nature 1022 21.15 Tertiary Structure 1022 MEDICAL CONNECTION: Diseases Caused by a Misfolded Protein 1024 21.16 Quaternary Structure 1024 21.17 Protein Denaturation 1025 ESSENTIAL CONCEPTS 1025 PROBLEMS 1026 22 Catalysis in Organic Reactions and in Enzymatic Reactions 1030 22.1 Catalysis in Organic Reactions 1032 22.2 Acid Catalysis 1032 22.3 Base Catalysis 1035 22.4 Nucleophilic Catalysis 1037 22.5 Metal-Ion Catalysis 1038 22.6 Intramolecular Reactions 1040 22.7 Intramolecular Catalysis 1042 22.8 Catalysis in Biological Reactions 1044 22.9 An Enzyme-Catalyzed Reaction That Is Reminiscent of Acid-Catalyzed Amide Hydrolysis 1046 22.10 Another Enzyme-Catalyzed Reaction That Is Reminiscent of Acid-Catalyzed Amide ­Hydrolysis 1049 22.11 An Enzyme-Catalyzed Reaction That Involves Two Sequential SN2 Reactions 1052 MEDICAL CONNECTION: How Tamiflu Works 1055 22.12 An Enzyme-Catalyzed Reaction That Is Reminiscent of the Base-Catalyzed Enediol ­Rearrangement 1056 22.13 An Enzyme Catalyzed-Reaction That Is Reminiscent of a Retro-Aldol Addition 1057 ESSENTIAL CONCEPTS 1059 PROBLEMS 1060 Increased emphasis on the connection between the reactions 23 The Organic Chemistry of the Coenzymes, Compounds Derived from Vitamins 1063 that occur in the laboratory and those that occur in cells. HISTORICAL CONNECTION: Vitamin B1 1065 23.1 Niacin: The Vitamin Needed for Many Redox Reactions 1066 HISTORICAL CONNECTION: Niacin Deficiency 1067 23.2 Riboflavin: Another Vitamin Used in Redox Reactions 1071 23.3 Vitamin B1: The Vitamin Needed for Acyl Group Transfer 1075 GENERAL CONNECTION: Curing a Hangover with Vitamin B1 1078 23.4 Biotin: The Vitamin Needed for Carboxylation of an a-Carbon 1079 23.5 Vitamin B6: The Vitamin Needed for Amino Acid Transformations 1081 MEDICAL CONNECTION: Assessing the Damage After a Heart Attack 1085 23.6 Vitamin B12: The Vitamin Needed for Certain Isomerizations 1086 23.7 Folic Acid: The Vitamin Needed for One-Carbon Transfer 1088 HISTORICAL CONNECTION: The First Antibiotics 1089 MEDICAL CONNECTION: Cancer Drugs and Side Effects 1092 BIOLOGICAL CONNECTION: Competitive Inhibitors 1092 23.8 Vitamin K: The Vitamin Needed for Carboxylation of Glutamate 1093 MEDICAL CONNECTION: Anticoagulants 1095 NUTRITIONAL CONNECTION: Too Much Broccoli 1095 ESSENTIAL CONCEPTS 1095 PROBLEMS 1096 24 The Organic Chemistry of the Metabolic Pathways 1099 NUTRITIONAL CONNECTION: Differences in Metabolism 1100 24.1 ATP is Used for Phosphoryl Transfer Reactions 1100 CHEMICAL CONNECTION: Why Did Nature Choose Phosphates? 1102 24.2 Why ATP is Kinetically Stable in a Cell 1102 24.3 The “High-Energy” Character of Phosphoanhydride Bonds 1102 24.4 The Four Stages of Catabolism 1104 24.5 The Catabolism of Fats: Stages 1 and 2 1105 24.6 The Catabolism of Carbohydrates: Stages 1 and 2 1108 P R O B L E M - S O LV I N G S T R AT E G Y 1111 xx NUTRITIONAL CONNECTION: Fats Versus Carbohydrates as a Source of Energy 1112 24.7 The Fate of Pyruvate 1112 24.8 The Catabolism of Proteins: Stages 1 and 2 1113 MEDICAL CONNECTION: Phenylketonuria (PKU): An Inborn Error of Metabolism 1114 MEDICAL CONNECTION: Alcaptonuria 1115 24.9 The Citric Acid Cycle: Stage 3 1115 24.10 Oxidative Phosphorylation: Stage 4 1118 NUTRITIONAL CONNECTION: Basal Metabolic Rate 1119 24.11 Anabolism 1119 24.12 Gluconeogenesis 1120 24.13 Regulating Metabolic Pathways 1122 24.14 Amino Acid Biosynthesis 1123 ESSENTIAL CONCEPTS 1124 PROBLEMS 1125 The lipid material previously in the chapter on carboxylic acids and their derivatives has been 25 The Organic Chemistry of Lipids 1127 moved into this new chapter. The 25.1 Fatty Acids Are Long-Chain Carboxylic Acids 1128 discussion of terpenes from the NUTRITIONAL CONNECTION: Omega Fatty Acids 1129 metabolism chapter has also been 25.2 Waxes Are High-Molecular-Weight Esters 1130 moved into this chapter, along with 25.3 Fats and Oils Are Triglycerides 1130 some new material. NUTRITIONAL CONNECTION: Olestra: Nonfat with Flavor 1132 BIOLOGICAL CONNECTION: Whales and Echolocation 1132 25.4 Soaps and Micelles 1132 25.5 Phospholipids Are Components of Cell Membranes 1134 BIOLOGICAL CONNECTION: Snake Venom 1136 MEDICAL CONNECTION: Multiple Sclerosis and the Myelin Sheath 1137 25.6 Prostaglandins Regulate Physiological Responses 1137 25.7 Terpenes Contain Carbon Atoms in Multiples of Five 1139 25.8 How Terpenes Are Biosynthesized 1141 MEDICAL CONNECTION: How Statins Lower Cholesterol Levels 1142 P R O B L E M - S O LV I N G S T R AT E G Y 1144 CHEMICAL CONNECTION: Protein Prenylation 1146 25.9 How Nature Synthesizes Cholesterol 1147 25.10 Steroids 1148 MEDICAL CONNECTION: One Drug—Two Effects 1149 25.11 Synthetic Steroids 1150 ESSENTIAL CONCEPTS 1151 PROBLEMS 1152 26 The Chemistry of the Nucleic Acids 1155 26.1 Nucleosides and Nucleotides 1155 HISTORICAL CONNECTION: The Structure of DNA: Watson, Crick, Franklin, and Wilkins 1158 BIOLOGICAL CONNECTION: Cyclic AMP 1159 26.2 Nucleic Acids Are Composed of Nucleotide Subunits 1159 26.3 The Secondary Structure of DNA 1161 26.4 Why DNA Does Not Have A 2′-OH Group 1163 26.5 The Biosynthesis of DNA Is Called Replication 1163 26.6 DNA and Heredity 1164 PHARMACEUTICAL CONNECTION: Natural Products That Modify DNA 1165 26.7 The Biosynthesis of RNA Is Called Transcription 1165 BIOLOGICAL CONNECTION: There Are More Than Four Bases in DNA 1166 26.8 The RNAs Used for Protein Biosynthesis 1167 26.9 The Biosynthesis of Proteins Is Called Translation 1169 MEDICAL CONNECTION: Sickle Cell Anemia 1171 MEDICAL CONNECTION: Antibiotics That Act by Inhibiting Translation 1172 26.10 Why DNA Contains Thymine Instead of Uracil 1173 MEDICAL CONNECTION: Antibiotics Act by a Common Mechanism 1174 26.11 Antiviral Drugs 1174 HISTORICAL CONNECTION: Influenza Pandemics 1175 26.12 How the Base Sequence of DNA Is Determined 1175 26.13 Genetic Engineering 1177  xxi   ENVIRONMENTAL CONNECTION: Resisting Herbicides 1177 PHARMACEUTICAL CONNECTION: Using Genetic Engineering to Treat the Ebola Virus 1177 ESSENTIAL CONCEPTS 1178 PROBLEMS 1178 PART Special Topics in Organic Chemistry 1181 EIGHT 27 Synthetic Polymers 1182 27.1 There Are Two Major Classes of Synthetic Polymers 1183 27.2 An Introduction To Chain-Growth Polymers 1184 27.3 Radical Polymerization 1184 INDUSTRIAL CONNECTION: Teflon: An Accidental Discovery 1187 ENVIRONMENTAL CONNECTION: Recycling Symbols 1189 27.4 Cationic Polymerization 1189 27.5 Anionic Polymerization 1192 27.6 Ring-Opening Polymerizations 1193 27.7 Stereochemistry of Polymerization Ziegler–Natta Catalysts 1195 27.8 Polymerization of Dienes 1196 27.9 Copolymers 1198 PHARMACEUTICAL CONNECTION: Nanocontainers 1198 27.10 An Introduction to Step-Growth Polymers 1199 27.11 Classes of Step-Growth Polymers 1200 MEDICAL CONNECTION: Health Concerns: Bisphenol A and Phthalates 1202 INDUSTRIAL CONNECTION: Designing a Polymer 1203 27.12 Physical Properties of Polymers 1204 NUTRITIONAL CONNECTION: Melamine Poisoning 1205 27.13 Recycling Polymers 1206 27.14 Biodegradable Polymers 1207 ESSENTIAL CONCEPTS 1208 PROBLEMS 1208 28 Pericyclic Reactions 1212 28.1 There Are Three Kinds of Pericyclic Reactions 1213 28.2 Molecular Orbitals and Orbital Symmetry 1215 28.3 Electrocyclic Reactions 1218 28.4 Cycloaddition Reactions 1224 28.5 Sigmatropic Rearrangements 1227 28.6 Pericyclic Reactions in Biological Systems 1232 CHEMICAL CONNECTION: Bioluminescence 1233 NUTRITIONAL CONNECTION: The Sunshine Vitamin 1234 NUTRITIONAL CONNECTION: Animals, Birds, Fish—And Vitamin D 1235 28.7 Summary of the Selection Rules for Pericyclic Reactions 1235 ESSENTIAL CONCEPTS 1236 PROBLEMS 1236 Appendices A-1 I PKA VALUES A-1 II KINETICS A-3 III SUMMARY OF METHODS USED TO SYNTHESIZE A PARTICULAR FUNCTIONAL GROUP A-8 IV SUMMARY OF METHODS EMPLOYED TO FORM CARBON-CARBON BONDS A-11 V SPECTROSCOPY TABLES A-12 VI PHYSICAL PROPERTIES OF ORGANIC COMPOUNDS A-18 ANSWERS TO SELECTED PROBLEMS ANS-1 GLOSSARY G-1 CREDITS C-1 INDEX I-1 Preface The guiding principle behind this book is to present organic chemistry as an exciting and vitally important science. To counter the impression that the study of organic chemistry consists primarily of memorizing a multitude of facts, I have organized this book around shared features and u­ nifying concepts, while emphasizing principles that can be applied again and again. I want students to apply what they have learned to new settings and to learn how to reason their way to solutions. I also want them to see that organic chemistry is a fascinating discipline that is integral to their daily lives. Preparing Students for Future Study in a Variety of Scientific Disciplines This book organizes the functional groups around mechanistic similarities. When students see their first reaction (other than an acid–base reaction), they are told that all organic compounds can be divided into families and that all members of a family react in the same way. And to make things even easier, each family can be put into one of four groups, and all the families in a group react in similar ways. “Organizing What We Know About Organic Chemistry” is a feature based on these ­statements. It lets students see where they have been and where they are going as they proceed through each of the four groups. It also encourages them to remember the fundamental reason behind the reactions of all organic compounds: electrophiles react with nucleophiles. When students finish studying a particular group, they are given the opportunity to review the group and understand why the families came to be members of that particular group. The four groups are covered in the following order. (However, the book is written to be modular, so they could be covered in any order.)   Group I: Compounds with carbon-carbon double and triple bonds. These compounds are nucleophiles and, therefore, react with electrophiles—undergoing electrophilic addition reactions.   Group II: Compounds with electron-withdrawing atoms or groups attached to sp3 ­carbons. These compounds are electrophiles and, therefore, react with nucleophiles—­ undergoing nucleophilic substitution and elimination reactions.  Group III: Carbonyl compounds. These compounds are electrophiles and, therefore, react with nucleophiles—undergoing nucleophilic acyl substitution, nucleophilic addition, and nucleophilic addition-elimination reactions. Because of the “acidity” of the a-carbon, a ­carbonyl compound can become a nucleophile and, therefore, react with electrophiles.