Principal Organic Chemistry
Organic ChemistryPaula Yurkanis Bruice
Paula Bruice’s presentation in Organic Chemistry, Eighth Edition provides mixed-science majors with the conceptual foundations, chemical logic, and problem-solving skills they need to reason their way to solutions for diverse problems in synthetic organic chemistry, biochemistry, and medicine. The Eighth Edition builds a strong framework for thinking about organic chemistry by unifying principles of reactivity that students will apply throughout the course, discouraging memorization. With more applications than any other textbook, Dr. Bruice consistently relates structure and reactivity to what occurs in our own cells and reinforces the fundamental reason for all chemical reactions–electrophiles react with nucleophiles. New streamlined coverage of substitution and elimination, updated problem-solving strategies, synthesis skill-building applications and tutorials guide students throughout fundamental and complex content in both the first and second semesters of the course.
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One of the best books on Organic Chemistry written by the pioneers of this field. A must read for every organic chemistry enthusiast.
27 December 2017 (18:26)
It is Very helpful for getting famous author's book in one platform.Thanks a lot z- library.
19 May 2019 (05:58)
One of the best book.
26 September 2019 (18:56)
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 thirdparty 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 CH APTER 1 CH APTER 2 Remembering General Chemistry: Electronic Structure and Bonding 2 Acids and Bases: Central to Understanding Organic Chemistry 50 T U TO R IAL Acids and Bases CH APTER 3 An Introduction to Organic Compounds: Nomenclature, Physical Properties, and Structure 80 88 T U TO R IAL Using Molecular Models CH APTER 4 Isomers: The Arrangement of Atoms in Space TU TO R IAL Interconverting Structural Representations CH APTER 5 Alkenes: Structure, Nomenclature, and an Introduction to Reactivity • Thermodynamics and Kinetics 190 T U TO R IAL Drawing Curved Arrows CH APTER 6 The Reactions of Alkenes • The Stereochemistry of Addition Reactions CH APTER 7 iv xxii 142 143 187 225 The Reactions of Alkynes • An Introduction to Multistep Synthesis 235 288 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 CH APTER 9 Substitution and Elimination Reactions of Alkyl Halides CH APTER 10 Reactions of Alcohols, Ethers, Epoxides, Amines, and Sulfur-Containing Compounds 458 CH APTER 11 Organometallic Compounds CH APTER 12 Radicals TU TO R IAL Drawing Curved Arrows in Radical Systems CH APTER 13 Mass Spectrometry; Infrared Spectroscopy; UV/Vis Spectroscopy 567 CH APTER 14 NMR Spectroscopy CHAPTER 15 Reactions of Carboxylic Acids and Carboxylic Acid Derivatives 382 391 508 532 563 620 686 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 TUTO R I A L Synthesis and Retrosynthetic Analysis C HA P TE R 1 8 Reactions of Benzene and Substituted Benzenes C HA P TE R 1 9 More About Amines • Reactions of Heterocyclic Compounds C HA P TE R 2 0 The Organic Chemistry of Carbohydrates C HA P TE R 2 1 Amino Acids, Peptides, and Proteins C HA P TE R 2 2 Catalysis in Organic Reactions and in Enzymatic Reactions 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 C HA P TE R 2 5 The Organic Chemistry of Lipids C HA P TE R 2 6 The Chemistry of the Nucleic Acids C HA P TE R 2 7 Synthetic Polymers C HA P TE R 2 8 Pericyclic Reactions A P P E ND I C E S I pKa 801 854 868 950 986 1099 1127 1155 1182 1212 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 A-11 Bonds V Spectroscopy Tables A-12 VI Physical Properties of Organic Compounds A-18 VII Answers to Selected Problems Glossary G-1 Photo Credits Index I-1 C-1 924 ANS-1 1030 Complete List of In-Chapter Connection Features Medical Connections Fosamax Prevents Bones from Being Nibbled Away (2.8) Aspirin Must Be in its Basic Form to be Physiologically Active (2.10) Blood: A Buffered Solution (2.11) Drugs Bind to Their Receptors (3.9) Cholesterol and Heart Disease (3.16) How High Cholesterol is Treated Clinically (3.16) The Enantiomers of Thalidomide (4.17) Synthetic Alkynes Are Used to Treat Parkinson’s Disease (7.0) Synthetic Alkynes Are Used for Birth Control (7.1) The Inability to Perform an SN2 Reaction Causes a Severe Clinical Disorder (10.3) Treating Alcoholism with Antabuse (10.5) Methanol Poisoning (10.5) Anesthetics (10.6) Alkylating Agents as Cancer Drugs (10.11) S-Adenosylmethionine: A Natural Antidepressant (10.12) Artificial Blood (12.12) Nature’s Sleeping Pill (15.1) Penicillin and Drug Resistance (15.12) Dissolving Sutures (15.13) Cancer Chemotherapy (16.17) Breast Cancer and Aromatase Inhibitors (17.12) Thyroxine (18.3) A New Cancer-Fighting Drug (18.20) Atropine (19.2) Porphyrin, Bilirubin, and Jaundice (19.7) Measuring the Blood Glucose Levels in Diabetes (20.8) Galactosemia (20.15) Why the Dentist is Right (20.16) Resistance to Antibiotics (20.17) Heparin–A Natural Anticoagulant (20.17) Amino Acids and Disease (21.2) Diabetes (21.8) Diseases Caused by a Misfolded Protein (21.15) How Tamiflu Works (22.11) Assessing the Damage After a Heart Attack (23.5) Cancer Drugs and Side Effects (23.7) Anticoagulants (23.8) Phenylketonuria (PKU): An Inborn Error of Metabolism (24.8) Alcaptonuria (24.8) Multiple Sclerosis and the Myelin Sheath (25.5) How Statins Lower Cholesterol Levels (25.8) One Drug—Two Effects (25.10) Sickle Cell Anemia (26.9) Antibiotics That Act by Inhibiting Translation (26.9) Antibiotics Act by a Common Mechanism (26.10) Health Concerns: Bisphenol A and Phthalates (27.11) Biological Connections Poisonous Amines (2.3) Cell Membranes (3.10) How a Banana Slug Knows What to Eat (7.2) Electron Delocalization Affects the Three-Dimensional Shape of Proteins (8.4) vi Naturally Occurring Alkyl Halides That Defend Against Predators (9.5) Biological Dehydrations (10.4) Alkaloids (10.9) Dalmatians: Do Not Fool with Mother Nature (15.11) A Semisynthetic Penicillin (15.12) Preserving Biological Specimens (16.9) A Biological Friedel-Crafts Alkylation (18.7) A Toxic Disaccharide (20.15) Controlling Fleas (20.16) Primary Structure and Taxonomic Relationship (21.12) Competitive Inhibitors (23.7) Whales and Echolocation (25.3) Snake Venom (25.5) Cyclic AMP (26.1) There Are More Than Four Bases in DNA (26.7) Chemical Connections Natural versus Synthetic Organic Compounds (1.0) Diamond, Graphite, Graphene, and Fullerenes: Substances that Contain Only Carbon Atoms (1.8) Water—A Unique Compound (1.12) Acid Rain (2.2) Derivation of the Henderson-Hasselbalch Equation (2.10) Bad-Smelling Compounds (3.7) Von Baeyer, Barbituric Acid, and Blue Jeans (3.12) Starch and Cellulose—Axial and Equatorial (3.14) Cis-Trans Interconversion in Vision (4.1) The Difference between ∆G‡ and Ea (5.11) Calculating Kinetic Parameters (End of Ch 05) Borane and Diborane (6.8) Cyclic Alkenes (6.13) Chiral Catalysts (6.15) Sodium Amide and Sodium in Ammonia (7.10) Buckyballs (8.18) Why Are Living Organisms Composed of Carbon Instead of Silicon? (9.2) Solvation Effects (9.14) The Lucas Test (10.1) Crown Ethers—Another Example of Molecular Recognition (10.7) Crown Ethers Can be Used to Catalyze SN2 Reactions (10.7) Eradicating Termites (10.12) Cyclopropane (12.9) What Makes Blueberries Blue and Strawberries Red? (13.22) Nerve Impulses, Paralysis, and Insecticides (15.19) Enzyme-Catalyzed Carbonyl Additions (16.4) Carbohydrates (16.9) b-Carotene (16.13) Synthesizing Organic Compounds (16.14) Enzyme-Catalyzed Cis-Trans Interconversion (16.16) Incipient Primary Carbocations (18.7) Hair: Straight or Curly? (21.8) Right-Handed and Left-Handed Helices (21.14) b-Peptides: An Attempt to Improve on Nature (21.14) Why Did Nature Choose Phosphates? (24.1) Protein Prenylation (25.8) Bioluminescence (28.6) vii Pharmaceutical Connections Chiral Drugs (4.18) Why Are Drugs so Expensive? (7.0) Lead Compounds for the Development of Drugs (10.9) Aspirin, NSAIDs, and COX-2 Inhibitors (15.9) Penicillins in Clinical Use (15.12) Serendipity in Drug Development (16.8) Semisynthetic Drugs (16.14) Drug Safety (18.19) Searching for Drugs: An Antihistamine, a Nonsedating Antihistamine, and a Drug for Ulcers (19.7) A Peptide Antibiotic (21.2) Natural Products That Modify DNA (26.6) Using Genetic Engineering to Treat the Ebola Virus (26.13) Nanocontainers (27.9) Historical Connections Kekule’s Dream (8.1) Mustard Gas–A Chemical Warfare Agent (10.11) Grubbs, Schrock, Suzuki, and Heck Receive the Nobel Prize (11.5) The Nobel Prize (11.5) Why Radicals No Longer Have to Be Called Free Radicals (12.2) Nikola Tesla (1856–1943) (14.1) The Discovery of Penicillin (15.12) Discovery of the First Antibiotic (18.19) Vitamin C (20.17) Vitamin B1 (23.0) Niacin Deficiency (23.1) The First Antibiotics (23.7) The Structure of DNA: Watson, Crick, Franklin, and Wilkins (26.1) Influenza Pandemics (26.11) Nutritional Connections Trans Fats (5.9) Decaffeinated Coffee and the Cancer Scare (12.11) Food Preservatives (12.11) Is Chocolate a Health Food? (12.11) Nitrosamines and Cancer (18.20) Lactose Intolerance (20.15) Acceptable Daily Intake (20.19) Proteins and Nutrition (21.1) Too Much Broccoli (23.8) Differences in Metabolism (24.0) Fats Versus Carbohydrates as a Source of Energy (24.6) Basal Metabolic Rate (24.10) Omega Fatty Acids (25.1) Olestra: Nonfat with Flavor (25.3) Melamine Poisoning (27.12) The Sunshine Vitamin (28.6) Animals, Birds, Fish—And Vitamin D (28.6) Industrial Connections How is the Octane Number of Gasoline Determined? (3.2) Organic Compounds That Conduct Electricity (8.7) Synthetic Polymers (15.13) The Synthesis of Aspirin (17.7) Teflon: An Accidental Discovery (27.3) Designing a Polymer (27.11) Environmental Connections Pheromones (5.0) Which are More Harmful: Natural Pesticides or Synthetic Pesticides? (6.16) Green Chemistry: Aiming for Sustainability (7.12) The Birth of the Environmental Movement (9.0) Environmental Adaptation (9.14) Benzo[a]pyrene and Cancer (10.8) Chimney Sweeps and Cancer (10.8) Resisting Herbicides (26.13) Recycling Symbols (27.3) General Connections A Few Words About Curved Arrows (5.5) Grain Alcohol and Wood Alcohol (10.1) Blood Alcohol Concentration (10.5) Natural Gas and Petroleum (12.1) Fossil Fuels: A Problematic Energy Source (12.1) Mass Spectrometry in Forensics (13.8) The Originator of Hooke’s Law (13.13) Ultraviolet Light and Sunscreens (13.19) Structural Databases (14.24) What Drug-Enforcement Dogs Are Really Detecting (15.16) Butanedione: An Unpleasant Compound (16.1) Measuring Toxicity (18.0) The Toxicity of Benzene (18.1) Glucose/Dextrose (20.9) Water Softeners: Examples of Cation-Exchange Chromatography (21.5) Curing a Hangover with Vitamin B1 (23.3) Contents PART ONE 1 1.1 1.2 1.3 1.4 An Introduction to the Study of Organic Chemistry Remembering General Chemistry: Electronic Structure and Bonding CHEMICAL CONNECTION: Natural versus Synthetic Organic Compounds The Structure of an Atom 4 How the Electrons in an Atom are Distributed 5 Covalent Bonds 7 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 1.5 1.6 1.7 1.8 1.9 1.10 1.11 1.12 1.13 1.14 2 ESSENTIAL CONCEPTS 2.3 46 ■ 2.4 2.5 2.6 2.7 An Introduction to Acids and Bases pKa and pH 52 2.11 of pH on Structure • Acids and Bases: Predicting the Position of Equilibrium viii 2.12 50 50 54 58 to Predict the Outcome of an Acid-Base Reaction 58 to Determine the Position of Equilibrium 59 the Structure of an Acid Affects its pKa Value 60 Substituents Affect the Strength of an Acid 64 64 An Introduction to Delocalized Electrons 66 MEDICAL CONNECTION: Fosamax Prevents Bones from Being Nibbled Away 67 68 A Summary of the Factors that Determine Acid Strength 69 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 • Acids and Bases: Definitions • Acids and Bases: Factors That Influence Acid Strength How How How How P R O B L E M - S O LV I N G S T R AT E G Y 2.9 2.10 47 CHEMICAL CONNECTION: Acid Rain 54 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 2.8 PROBLEMS Acids and Bases: Central to Understanding Organic Chemistry P R O B L E M - S O LV I N G S T R AT E G Y • Acids and Bases: Base Strength and the Effect 44 Dipole Moments of Molecules 44 P R O B L E M - S O LV I N G S T R AT E G Y for Organic Chemistry 39 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 MasteringChemistry tutorials guide you through the toughest topics in chemistry with self-paced tutorials that provide individualized coaching. These assignable, in-depth tutorials are designed to coach you with hints and feedback specific to your individual misconceptions. For additional practice on Acids and Bases, go to MasteringChemistry, where the following tutorials are available: 15 1.16 2.1 2.2 3 Atomic Orbitals 19 An Introduction to Molecular Orbital Theory 21 How Single Bonds are Formed in Organic Compounds 25 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 How a Triple Bond is Formed: The Bonds in Ethyne 31 The Bonds in the Methyl Cation, the Methyl Radical, and the Methyl Anion 33 The Bonds in Ammonia and in the Ammonium Ion 35 The Bonds in Water 36 CHEMICAL CONNECTION: Water—A Unique Compound 37 The Bond in a Hydrogen Halide 38 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 1.15 2 71 CHEMICAL CONNECTION: Derivation of the Henderson-Hasselbalch Equation 72 MEDICAL CONNECTION: Aspirin Must Be in its Basic Form to be Physiologically Active Buffer Solutions 74 MEDICAL CONNECTION: Blood: A Buffered Solution 75 Lewis Acids and Bases 76 ESSENTIAL CONCEPTS 77 TUTORIAL Acids and Bases ■ 80 PROBLEMS 77 74 1 3 An Introduction to Organic Compounds: Nomenclature, Physical Properties, and Structure 3.3 Alkyl Groups 92 The Nomenclature of Alkanes 95 INDUSTRIAL CONNECTION: How is the Octane Number of Gasoline Determined? 98 The Nomenclature of Cycloalkanes 99 3.1 3.2 101 P R O B L E M - S O LV I N G S T R AT E G Y 3.4 3.5 3.6 3.7 3.8 3.9 The Nomenclature of Alkyl Halides 101 The Nomenclature of Ethers 103 The Nomenclature of Alcohols 104 The Nomenclature of Amines 106 CHEMICAL CONNECTION: Bad-Smelling Compounds 109 The Structures of Alkyl Halides, Alcohols, Ethers, and Amines 109 Noncovalent Interactions 110 114 P R O B L E M - S O LV I N G S T R AT E G Y 3.10 3.11 3.12 MEDICAL CONNECTION: Drugs Bind to Their Receptors 114 The Solubility of Organic Compounds 116 BIOLOGICAL CONNECTION: Cell Membranes 118 Rotation Occurs about Carbon–Carbon Single Bonds 118 Some Cycloalkanes Have Angle Strain 122 CHEMICAL CONNECTION: Von Baeyer, Barbituric Acid, and Blue Jeans 123 123 P R O B L E M - S O LV I N G S T R AT E G Y 3.13 3.14 3.15 3.16 Conformers of Cyclohexane 124 Conformers of Monosubstituted Cyclohexanes 127 CHEMICAL CONNECTION: Starch and Cellulose—Axial and Equatorial 128 Conformers of Disubstituted Cyclohexanes 129 P R O B L E M - S O LV I N G S T R AT E G Y 130 P R O B L E M - S O LV I N G S T R AT E G Y 132 Fused Cyclohexane Rings 134 MEDICAL CONNECTION: Cholesterol and Heart Disease 134 MEDICAL CONNECTION: How High Cholesterol is Treated Clinically 135 ESSENTIAL CONCEPTS PART TWO 135 ■ PROBLEMS 4.1 4.2 4.9 4.10 4.11 4.12 4.13 • Basics of Model Building • Building and Recognizing Chiral Molecules • Recognizing Chirality in Cyclic Molecules 142 143 Cis–Trans Isomers Result from Restricted Rotation 145 CHEMICAL CONNECTION: Cis-Trans Interconversion in Vision 147 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 157 P R O B L E M - S O LV I N G S T R AT E G Y 158 Chiral Compounds Are Optically Active 159 How Specific Rotation Is Measured 161 Enantiomeric Excess 163 Compounds with More than One Asymmetric Center 164 Stereoisomers of Cyclic Compounds 166 168 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 Using the E,Z system to name alkenes was moved to Chapter 4, so now it appears immediately after using cis and trans to distinguish alkene stereoisomers. 150 A Chiral Object Has a Nonsuperimposable Mirror Image 150 An Asymmetric Center is a Cause of Chirality in a Molecule 151 Isomers with One Asymmetric Center 152 Asymmetric Centers and Stereocenters 153 How to Draw Enantiomers 153 Naming Enantiomers by the R,S System 154 P R O B L E M - S O LV I N G S T R AT E G Y 4.14 Mastering Chemistry tutorials guide you through the toughest topics in chemistry with self-paced tutorials that provide individualized coaching. These assignable, in-depth tutorials are designed to coach you with hints and feedback specific to your individual misconceptions. For additional practice on Molecular Models, go to MasteringChemistry where the following tutorials are available: 136 Isomers: The Arrangement of Atoms in Space P R O B L E M - S O LV I N G S T R AT E G Y 4.3 4.4 4.5 4.6 4.7 4.8 for Organic Chemistry E lectrophilic Addition Reactions, Stereochemistry, and Electron Delocalization 141 TUTORIAL Using Molecular Models 4 88 171 for Organic Chemistry MasteringChemistry tutorials guide you through the toughest topics in chemistry with self-paced tutorials that provide individualized coaching. These assignable, in-depth tutorials are designed to coach you with hints and feedback specific to your individual misconceptions. For additional practice on Interconverting Structural Representations, go to MasteringChemistry where the following tutorials are available: • Interconverting Fischer Projections and Perspective Formulas • Interconverting Perspective Formulas, Fischer Projections, and Skeletal Structures • Interconverting Perspective Formulas, Fischer Projections, and Newman Projections x 4.15 How to Name Isomers with More than One Asymmetric Center 172 175 P R O B L E M - S O LV I N G S T R AT E G Y 4.16 4.17 4.18 Nitrogen and Phosphorus Atoms Can Be Asymmetric Centers 177 Receptors 178 MEDICAL CONNECTION: The Enantiomers of Thalidomide 179 How Enantiomers Can Be Separated 179 PHARMACEUTICAL CONNECTION: Chiral Drugs 180 ESSENTIAL CONCEPTS 181 PROBLEMS ■ 181 TUTORIAL Interconverting Structural Representations Catalytic hydrogenation and relative stabilities of alkenes were moved from Chapter 6 to Chapter 5 (thermodynamics), so they can be used to illustrate how ΔH° values can be used to determine relative stabilities. 5 Alkenes: Structure, Nomenclature, and an Introduction to Reactivity • Thermodynamics and Kinetics 190 5.1 5.2 5.3 ENVIRONMENTAL CONNECTION: Pheromones 191 Molecular Formulas and the Degree of Unsaturation 191 The Nomenclature of Alkenes 192 The Structure of Alkenes 195 196 P R O B L E M - S O LV I N G S T R AT E G Y 5.4 5.5 for Organic Chemistry MasteringChemistry tutorials guide you through the toughest topics in chemistry with self-paced tutorials that provide individualized coaching. These assignable, in-depth tutorials are designed to coach you with hints and feedback specific to your individual misconceptions. For additional practice on Drawing Curved Arrows: Pushing Electrons, go to MasteringChemistry where the following tutorials are available: • An Exercise in Drawing Curved Arrows: Pushing Electrons • An Exercise in Drawing Curved Arrows: Predicting Electron Movement 5.6 5.7 5.8 5.9 How An Organic Compound Reacts Depends on Its Functional Group 197 How Alkenes React • Curved Arrows Show the Flow of Electrons 198 GENERAL CONNECTION: A Few Words About Curved Arrows 200 Thermodynamics: How Much Product is Formed? 202 Increasing the Amount of Product Formed in a Reaction 205 Calculating ∆H ° Values 206 Using ∆H ° Values to Determine the Relative Stabilities of Alkenes 207 208 P R O B L E M - S O LV I N G S T R AT E G Y 5.10 5.11 5.12 5.13 5.14 • An Exercise in Drawing Curved Arrows: NUTRITIONAL CONNECTION: Trans Fats 211 Kinetics: How Fast is the Product Formed? 211 The Rate of a Chemical Reaction 213 CHEMICAL CONNECTION: The Difference between ∆G ‡ and Ea 215 A Reaction Coordinate Diagram Describes the Energy Changes That Take Place During a Reaction 215 Catalysis 218 Catalysis by Enzymes 219 ESSENTIAL CONCEPTS Interpreting Electron Movement 220 PROBLEMS ■ 221 CHEMICAL CONNECTION: Calculating Kinetic Parameters TUTORIAL Drawing Curved Arrows All the reactions in Chapter 6 follow the same mechanism the first step is always addition of the electrophile to the sp2 carbon bonded to the most hydrogens. 187 6 6.1 6.2 6.3 6.4 6.9 257 The Addition of a Peroxyacid to an Alkene 257 The Addition of Ozone to an Alkene: Ozonolysis 259 261 Regioselective, Stereoselective, And Stereospecific Reactions 263 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 6.14 243 The Addition of Water to an Alkene 245 The Addition of an Alcohol to an Alkene 246 A Carbocation Will Rearrange if It Can Form a More Stable Carbocation 248 The Addition of Borane to an Alkene: Hydroboration–Oxidation 250 CHEMICAL CONNECTION: Borane and Diborane 251 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 6.12 6.13 235 The Addition of a Hydrogen Halide to an Alkene 236 Carbocation Stability Depends on the Number of Alkyl Groups Attached to the Positively Charged Carbon 237 What Does the Structure of the Transition State Look Like? 239 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 6.10 6.11 225 The Reactions of Alkenes • The Stereochemistry of Addition Reactions P R O B L E M - S O LV I N G S T R AT E G Y 6.5 6.6 6.7 6.8 224 274 The Stereochemistry of Enzyme-Catalyzed Reactions 276 xi 6.15 6.16 Enantiomers Can Be Distinguished by Biological Molecules 277 CHEMICAL CONNECTION: Chiral Catalysts 278 Reactions and Synthesis 278 ENVIRONMENTAL CONNECTION: Which are More Harmful: Natural Pesticides or Synthetic Pesticides? 280 ESSENTIAL CONCEPTS 7 7.1 7.2 7.3 7.4 7.5 7.6 7.7 7.8 7.9 7.10 280 ■ 8.1 8.2 8.3 8.4 8.5 8.7 8.8 8.9 312 288 305 ■ SUMMARY OF REACTIONS 313 ■ 312 PROBLEMS 314 Delocalized Electrons Explain Benzene’s Structure 319 HISTORICAL CONNECTION: Kekule’s Dream 321 The Bonding in Benzene 321 Resonance Contributors and the Resonance Hybrid 322 How to Draw Resonance Contributors 323 BIOLOGICAL CONNECTION: Electron Delocalization Affects the Three-Dimensional Shape of Proteins 326 The Predicted Stabilities of Resonance Contributors 326 328 Delocalization Energy is the Additional Stability Delocalized Electrons Give to a Compound 329 Delocalized Electrons Increase Stability 330 INDUSTRIAL CONNECTION: Organic Compounds That Conduct Electricity A Molecular Orbital Description of Stability 335 Delocalized Electrons Affect pKa Values 339 342 Electronic Effects 342 Delocalized Electrons Can Affect the Product of a Reaction 346 Reactions of Dienes 347 Thermodynamic Versus Kinetic Control 350 The Diels–Alder Reaction is a 1,4-Addition Reaction 355 Retrosynthetic Analysis of the Diels–Alder Reaction 361 Benzene is an Aromatic Compound 362 The Two Criteria for Aromaticity 363 Applying the Criteria for Aromaticity 364 CHEMICAL CONNECTION: Buckyballs 365 P R O B L E M - S O LV I N G S T R AT E G Y 8.19 282 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 P R O B L E M - S O LV I N G S T R AT E G Y 8.10 8.11 8.12 8.13 8.14 8.15 8.16 8.17 8.18 PROBLEMS Synthesis Using Acetylide Ions 306 DESIGNING A SYNTHESIS I: An Introduction to Multistep Synthesis 307 ENVIRONMENTAL CONNECTION: Green Chemistry: Aiming for Sustainability P R O B L E M - S O LV I N G S T R AT E G Y 8.6 ■ MEDICAL CONNECTION: Synthetic Alkynes Are Used to Treat Parkinson’s Disease 289 PHARMACEUTICAL CONNECTION: Why Are Drugs so Expensive? 290 The Nomenclature of Alkynes 290 MEDICAL CONNECTION: Synthetic Alkynes Are Used for Birth Control 291 How to Name a Compound That Has More than One Functional Group 292 The Structure of Alkynes 293 BIOLOGICAL CONNECTION: How a Banana Slug Knows What to Eat 293 The Physical Properties of Unsaturated Hydrocarbons 294 The Reactivity of Alkynes 295 The Addition of Hydrogen Halides and the Addition of Halogens to an Alkyne 296 The Addition of Water to an Alkyne 299 The Addition of Borane to an Alkyne: Hydroboration–Oxidation 301 The Addition of Hydrogen to an Alkyne 302 A Hydrogen Bonded to an sp Carbon Is “Acidic” 304 CHEMICAL CONNECTION: Sodium Amide and Sodium in Ammonia 305 ESSENTIAL CONCEPTS 8 281 The Reactions of Alkynes • An Introduction to Multistep Synthesis P R O B L E M - S O LV I N G S T R AT E G Y 7.11 7.12 SUMMARY OF REACTIONS 366 A Molecular Orbital Description of Aromaticity 367 Chapter 8 starts by discussing the structure of benzene because it is the ideal compound to use to explain delocalized electrons. This chapter also includes a discussion of aromaticity, so a short introduction to electrophilic aromatic substitution reactions is now included. This allows students to see how aromaticity causes benzene to undergo electrophilic substitution rather than electrophilic addition— the reactions they have just finished studying. Traditionally, electronic effects are taught so students can understand the directing effects of substituents on benzene rings. Now that most of the chemistry of benzene follows carbonyl chemistry, students need to know about electronic effects before they get to benzene chemistry (so they are better prepared for spectroscopy and carbonyl chemistry). Therefore, electronic effects are now discussed in Chapter 8 and used to teach students how substituents affect the pKa values of phenols, benzoic acids, and anilinium ions. Electronic effects are then reviewed in the chapter on benzene. 333 for Organic Chemistry MasteringChemistry tutorials guide you through the toughest topics in chemistry with self-paced tutorials that provide individualized coaching. These assignable, in-depth tutorials are designed to coach you with hints and feedback specific to your individual misconceptions. For additional practice on Drawing Resonance Contributors, go to MasteringChemistry where the following tutorials are available: • Drawing Resonance Contributors: Moving p Electrons • Drawing Resonance Contributors: Predicting Aromaticity • Drawing Resonance Contributors: Substituted Benzene Rings xii 8.20 8.21 8.22 Aromatic Heterocyclic Compounds 368 How Benzene Reacts 370 Organizing What We Know About the Reactions of Organic Compounds (Group I) 372 ESSENTIAL CONCEPTS 373 ■ SUMMARY OF REACTIONS TUTORIAL Drawing Resonance Contributors PART THREE The two chapters in the previous edition on substitution and elimination reactions of alkenes have been combined into one chapter. The recent compelling evidence showing that secondary alkyl halides do not undergo SN1 solvolysis reactions has allowed this material to be greatly simplified, so now it fits nicely into one chapter. 9 9.1 9.2 9.3 9.4 9.5 9.14 9.15 9.16 10.1 10.2 10.3 10.4 421 425 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 Solvent Effects 438 CHEMICAL CONNECTION: Solvation Effects 438 ENVIRONMENTAL CONNECTION: Environmental Adaptation 441 Substitution and Elimination Reactions in Synthesis 442 Intermolecular Versus Intramolecular Reactions 444 446 DESIGNING A SYNTHESIS II: Approaching the Problem 446 449 405 411 Elimination from Substituted Cyclohexanes 427 Predicting the Products of the Reaction of an Alkyl Halide with a Nucleophile/Base 429 Benzylic Halides, Allylic Halides, Vinylic Halides, and Aryl Halides 433 ■ SUMMARY OF REACTIONS 450 ■ PROBLEMS eactions of Alcohols, Ethers, Epoxides, Amines, and R Sulfur-Containing Compounds 458 Nucleophilic Substitution Reactions of Alcohols: Forming Alkyl Halides 459 CHEMICAL CONNECTION: The Lucas Test 461 GENERAL CONNECTION: Grain Alcohol and Wood Alcohol 462 Other Methods Used to Convert Alcohols into Alkyl Halides 463 Converting an Alcohol Into a Sulfonate Ester 465 MEDICAL CONNECTION: The Inability to Perform an SN2 Reaction Causes a Severe Clinical Disorder 467 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 10.5 391 Competition Between E2 and E1 Reactions 422 E2 and E1 Reactions are Stereoselective 423 ESSENTIAL CONCEPTS 10 390 BIOLOGICAL CONNECTION: Naturally Occurring Alkyl Halides That Defend Against Predators Elimination Reactions of Alkyl Halides 412 The E2 Reaction 413 The E1 Reaction 419 P R O B L E M - S O LV I N G S T R AT E G Y 9.17 375 ENVIRONMENTAL CONNECTION: The Birth of the Environmental Movement 392 The SN2 Reaction 393 Factors That Affect SN2 Reactions 398 CHEMICAL CONNECTION: Why Are Living Organisms Composed of Carbon Instead of Silicon? The SN1 Reaction 406 Factors That Affect SN1 Reactions 409 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 9.11 9.12 9.13 PROBLEMS 382 Substitution and Elimination Reactions of Alkyl Halides P R O B L E M - S O LV I N G S T R AT E G Y 9.9 9.10 ■ Substitution and Elimination Reactions P R O B L E M - S O LV I N G S T R AT E G Y 9.6 9.7 9.8 374 471 BIOLOGICAL CONNECTION: Biological Dehydrations 473 Oxidation of Alcohols 474 GENERAL CONNECTION: Blood Alcohol Concentration 476 MEDICAL CONNECTION: Treating Alcoholism with Antabuse MEDICAL CONNECTION: Methanol Poisoning 477 476 451 412 xiii 10.6 10.7 10.8 10.9 10.10 10.11 10.12 10.13 Nucleophilic Substitution Reactions of Ethers 477 MEDICAL CONNECTION: Anesthetics 478 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 Arene Oxides 485 ENVIRONMENTAL CONNECTION: Benzo[a]pyrene and Cancer 488 ENVIRONMENTAL CONNECTION: Chimney Sweeps and Cancer 489 Amines Do Not Undergo Substitution or Elimination Reactions 490 BIOLOGICAL CONNECTION: Alkaloids 491 PHARMACEUTICAL CONNECTION: Lead Compounds for the Development of Drugs 491 Quaternary Ammonium Hydroxides Undergo Elimination Reactions 492 Thiols, Sulfides, and Sulfonium Ions 494 HISTORICAL CONNECTION: Mustard Gas–A Chemical Warfare Agent 495 MEDICAL CONNECTION: Alkylating Agents as Cancer Drugs 496 Methylating Agents Used by Chemists versus Those Used by Cells 496 CHEMICAL CONNECTION: Eradicating Termites 497 MEDICAL CONNECTION: S-Adenosylmethionine: A Natural Antidepressant 498 Organizing What We Know About the Reactions of Organic Compounds (Group II) 499 ESSENTIAL CONCEPTS 11 11.1 11.2 11.3 11.4 500 ■ Organometallic Compounds 12.1 12.2 12.3 12.4 12.5 ■ PROBLEMS 503 508 The discussion of palladiumcatalyzed coupling reactions has been expanded, and the cyclic catalytic mechanisms are shown. 521 Alkene Metathesis 522 HISTORICAL CONNECTION: Grubbs, Schrock, Suzuki, and Heck Receive the Nobel Prize 526 HISTORICAL CONNECTION: The Nobel Prize 526 ESSENTIAL CONCEPTS 12 501 Organolithium and Organomagnesium Compounds 509 Transmetallation 511 Organocuprates 512 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 11.5 SUMMARY OF REACTIONS Radicals 527 ■ SUMMARY OF REACTIONS 527 ■ PROBLEMS 528 532 Alkanes are Unreactive Compounds 532 GENERAL CONNECTION: Natural Gas and Petroleum 533 GENERAL CONNECTION: Fossil Fuels: A Problematic Energy Source 533 The Chlorination and Bromination of Alkanes 534 HISTORICAL CONNECTION: Why Radicals No Longer Have to Be Called Free Radicals 536 Radical Stability Depends on the Number of Alkyl Groups Attached to the Carbon with the Unpaired Electron 536 The Distribution of Products Depends on Probability and Reactivity 537 The Reactivity–Selectivity Principle 539 541 P R O B L E M - S O LV I N G S T R AT E G Y 12.6 12.7 12.8 12.9 MasteringChemistry tutorials guide you through the toughest topics in chemistry with self-paced tutorials that provide individualized coaching. These assignable, in-depth tutorials are designed to coach you with hints and feedback specific to your individual misconceptions. For additional practice on Drawing Curved Arrows in Radical Systems, go to MasteringChemistry where the following tutorials are available: Formation of Explosive Peroxides 542 The Addition of Radicals to an Alkene 543 The Stereochemistry of Radical Substitution and Radical Addition Reactions 546 Radical Substitution of Allylic and Benzylic Hydrogens 547 CHEMICAL CONNECTION: Cyclopropane 550 12.10 DESIGNING A SYNTHESIS III: More Practice with Multistep Synthesis 550 12.11 Radical Reactions in Biological Systems 552 NUTRITIONAL CONNECTION: Decaffeinated Coffee and the Cancer Scare 553 NUTRITIONAL CONNECTION: Food Preservatives 555 NUTRITIONAL CONNECTION: Is Chocolate a Health Food? 556 12.12 Radicals and Stratospheric Ozone 556 MEDICAL CONNECTION: Artificial Blood 558 ESSENTIAL CONCEPTS 558 ■ SUMMARY OF REACTIONS TUTORIAL Drawing Curved Arrows in Radical Systems 559 563 ■ PROBLEMS for Organic Chemistry • Curved Arrows in Radical Systems: Interpreting Curved Arrows • Curved Arrows in Radical Systems: Drawing Curved Arrows • Curved Arrows in Radical Systems: Drawing 559 Resonance Contributors xiv PART FOUR In addition to the more than 170 spectroscopy problems in Chapters 13 and 14, there are 60 additional spectroscopy problems in the Study Guide and Solutions Manual. 13 13.1 13.2 13.3 Identification of Organic Compounds Mass Spectrometry; Infrared Spectroscopy; UV/Vis Spectroscopy Mass Spectrometry 569 The Mass Spectrum • Fragmentation 570 Using The m/z Value of the Molecular Ion to Calculate the Molecular Formula 572 573 P R O B L E M - S O LV I N G S T R AT E G Y Chapters 13 and 14 are modular, so they can be covered at any time. 13.4 13.5 13.6 13.7 13.8 13.9 13.10 13.11 13.12 13.13 13.14 Isotopes in Mass Spectrometry 574 High-Resolution Mass Spectrometry Can Reveal Molecular Formulas 575 The Fragmentation Patterns of Functional Groups 575 Other Ionization Methods 583 Gas Chromatography–Mass Spectrometry 583 GENERAL CONNECTION: Mass Spectrometry in Forensics 583 Spectroscopy and the Electromagnetic Spectrum 583 Infrared Spectroscopy 585 Characteristic Infrared Absorption Bands 588 The Intensity of Absorption Bands 589 The Position of Absorption Bands 590 GENERAL CONNECTION: The Originator of Hooke’s Law 590 The Position and Shape of an Absorption Band is Affected by Electron Delocalization and Hydrogen Bonding 591 593 P R O B L E M - S O LV I N G S T R AT E G Y 13.15 13.16 13.17 13.18 13.19 13.20 13.21 13.22 13.23 C ¬ H Absorption Bands 595 The Absence of Absorption Bands 598 Some Vibrations are Infrared Inactive 599 How to Interpret an Infrared Spectrum 600 Ultraviolet and Visible Spectroscopy 602 GENERAL CONNECTION: Ultraviolet Light and Sunscreens 603 The Beer–Lambert Law 604 The Effect of Conjugation on lmax 605 The Visible Spectrum and Color 606 CHEMICAL CONNECTION: What Makes Blueberries Blue and Strawberries Red? 607 Some Uses of UV/Vis Spectroscopy 608 ESSENTIAL CONCEPTS 14 14.1 14.2 14.3 14.4 NMR Spectroscopy 610 14.10 14.11 14.12 14.13 ■ PROBLEMS 611 620 An Introduction to NMR Spectroscopy 620 HISTORICAL CONNECTION: Nikola Tesla (1856–1943) 622 Fourier Transform NMR 623 Shielding Causes Different Nuclei to Show Signals at Different Frequencies 623 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 14.5 14.6 14.7 14.8 14.9 566 625 The Chemical Shift Tells How Far the Signal Is from the Reference Signal 626 The Relative Positions of 1H NMR Signals 628 The Characteristic Values of Chemical Shifts 629 Diamagnetic Anisotropy 631 The Integration of NMR Signals Reveals the Relative Number of Protons Causing Each Signal 632 The Splitting of Signals Is Described by the N + 1 Rule 634 What Causes Splitting? 637 More Examples of 1H NMR Spectra 639 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 14.15 Enantiotopic and Diastereotopic Hydrogens 650 14.16 The Time Dependence of NMR Spectroscopy 652 647 567 xv 14.17 Protons Bonded to Oxygen and Nitrogen 652 14.18 The Use of Deuterium in 1H NMR Spectroscopy 14.19 The Resolution of 1H NMR Spectra 655 14.20 13C NMR Spectroscopy 657 660 P R O B L E M - S O LV I N G S T R AT E G Y 14.21 14.22 14.23 14.24 Dept 13C NMR Spectra 662 Two-Dimensional NMR Spectroscopy 662 NMR Used in Medicine is Called Magnetic Resonance Imaging 665 X-Ray Crystallography 666 GENERAL CONNECTION: Structural Databases 667 ESSENTIAL CONCEPTS PART FIVE 15 15.1 15.2 15.3 15.4 654 668 ■ PROBLEMS Carbonyl Compounds 669 The focus of the first chapter on carbonyl chemistry is all about how a tetrahedral intermediate partitions. If students understand this, then carbonyl chemistry becomes pretty straightforward. I found that the lipid materil that had been put into this chapter in the last edition detracted from the main message of the chapter. Therefore, the lipid material was removed and put into a new chapter exclusively about lipids. 685 Reactions of Carboxylic Acids and Carboxylic Acid Derivatives 686 The Nomenclature of Carboxylic Acids and Carboxylic Acid Derivatives 688 MEDICAL CONNECTION: Nature’s Sleeping Pill 691 The Structures of Carboxylic Acids and Carboxylic Acid Derivatives 692 The Physical Properties of Carbonyl Compounds 693 How Carboxylic Acids and Carboxylic Acid Derivatives React 694 696 P R O B L E M - S O LV I N G S T R AT E G Y 15.5 15.6 15.7 15.8 15.9 The Relative Reactivities of Carboxylic Acids and Carboxylic Acid Derivatives 696 Reactions of Acyl Chlorides 698 Reactions of Esters 701 Acid-Catalyzed Ester Hydrolysis and Transesterification 702 Hydroxide-Ion-Promoted Ester Hydrolysis 706 PHARMACEUTICAL CONNECTION: Aspirin, NSAIDs, and COX-2 Inhibitors 707 15.10 Reactions of Carboxylic Acids 709 710 P R O B L E M - S O LV I N G S T R AT E G Y 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 Penicillin 713 Resistance 713 15.13 15.14 15.15 15.16 15.17 15.18 15.19 HISTORICAL CONNECTION: The Discovery of MEDICAL CONNECTION: Penicillin and Drug PHARMACEUTICAL CONNECTION: Penicillins in Clinical Use 714 BIOLOGICAL CONNECTION: A Semisynthetic Penicillin 714 Hydroxide-Ion-Promoted Hydrolysis of Amides 715 INDUSTRIAL CONNECTION: Synthetic Polymers 715 MEDICAL CONNECTION: Dissolving Sutures 716 Hydrolysis of an Imide: a Way to Synthesize a Primary Amine 716 Nitriles 717 Acid Anhydrides 719 GENERAL CONNECTION: What Drug-Enforcement Dogs Are Really Detecting Dicarboxylic Acids 721 How Chemists Activate Carboxylic Acids 723 How Cells Activate Carboxylic Acids 724 CHEMICAL CONNECTION: Nerve Impulses, Paralysis, and Insecticides 727 ESSENTIAL CONCEPTS 16 16.1 16.2 16.3 728 ■ SUMMARY OF REACTIONS 729 ■ 721 PROBLEMS Reactions of Aldehydes and Ketones • More Reactions of Carboxylic Acid Derivatives 739 The Nomenclature of Aldehydes and Ketones 740 GENERAL CONNECTION: Butanedione: An Unpleasant Compound The Relative Reactivities of Carbonyl Compounds 743 How Aldehydes and Ketones React 744 742 731 xvi 16.4 Reactions of Carbonyl Compounds with Carbon Nucleophiles 745 CHEMICAL CONNECTION: Enzyme-Catalyzed Carbonyl Additions 747 749 P R O B L E M - S O LV I N G S T R AT E G Y 16.5 16.6 16.7 16.8 16.9 Reactions of Carbonyl Compounds with Hydride Ion 752 More About Reduction Reactions 757 Chemoselective Reactions 759 Reactions of Aldehydes and Ketones with Nitrogen Nucleophiles 760 PHARMACEUTICAL CONNECTION: Serendipity in Drug Development 765 Reactions of Aldehydes and Ketones with Oxygen Nucleophiles 766 BIOLOGICAL CONNECTION: Preserving Biological Specimens 768 CHEMICAL CONNECTION: Carbohydrates 770 771 P R O B L E M - S O LV I N G S T R AT E G Y 16.10 16.11 16.12 16.13 16.14 16.15 16.16 16.17 Protecting Groups 772 Reactions of Aldehydes and Ketones with Sulfur Nucleophiles 774 Reactions of Aldehydes and Ketones with a Peroxyacid 774 The Wittig Reaction Forms an Alkene 776 CHEMICAL CONNECTION: b-Carotene 777 DESIGNING A SYNTHESIS IV: Disconnections, Synthons, and Synthetic Equivalents 779 CHEMICAL CONNECTION: Synthesizing Organic Compounds 781 PHARMACEUTICAL CONNECTION: Semisynthetic Drugs 781 Nucleophilic Addition to a,b-Unsaturated Aldehydes and Ketones 781 Nucleophilic Addition to a,b-Unsaturated Carboxylic Acid Derivatives 785 CHEMICAL CONNECTION: Enzyme-Catalyzed Cis-Trans Interconversion 785 Conjugate Addition Reactions in Biological Systems 786 MEDICAL CONNECTION: Cancer Chemotherapy 786 ESSENTIAL CONCEPTS This chapter was reorganized and rewritten for ease of understanding. 17 17.1 787 ■ Reactions at the A-Carbon 17.12 17.13 17.14 17.15 17.16 PROBLEMS 791 801 804 813 Alkylating and Acylating the a-Carbon Via an Enamine Intermediate 814 Alkylating the b-Carbon 815 An Aldol Addition Forms a b-Hydroxyaldehyde or a b-Hydroxyketone 817 The Dehydration of Aldol Addition Products Forms a,b-Unsaturated Aldehydes and Ketones 819 A Crossed Aldol Addition 821 MEDICAL CONNECTION: Breast Cancer and Aromatase Inhibitors 823 A Claisen Condensation Forms a b-Keto Ester 824 Other Crossed Condensations 827 Intramolecular Condensations and Intramolecular Aldol Additions 827 The Robinson Annulation 830 830 P R O B L E M - S O LV I N G S T R AT E G Y 17.17 17.18 17.19 17.20 17.21 17.22 ■ Keto–Enol Tautomers 805 Keto–Enol Interconversion 806 Halogenation of the a-Carbon of Aldehydes and Ketones 807 Halogenation of the a-Carbon of Carboxylic Acids 809 Forming an Enolate Ion 810 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 17.8 17.9 17.10 17.11 788 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 17.2 17.3 17.4 17.5 17.6 17.7 SUMMARY OF REACTIONS CO2 Can be Removed from a Carboxylic Acid that has a Carbonyl Group at the 3-Position 831 The Malonic Ester Synthesis: A Way to Synthesize a Carboxylic Acid 833 The Acetoacetic Ester Synthesis: A Way to Synthesize a Methyl Ketone 834 DESIGNING A SYNTHESIS V: Making New Carbon–Carbon Bonds 836 Reactions at the a-Carbon in Living Systems 838 Organizing What We Know About the Reactions of Organic Compounds (Group III) 841 ESSENTIAL CONCEPTS 843 ■ SUMMARY OF REACTIONS TUTORIAL Synthesis and Retrosynthetic Analysis 854 844 ■ PROBLEMS 846 xvii PART SIX 18 18.1 18.2 18.3 18.4 18.5 18.6 18.7 18.8 18.9 18.10 18.11 18.12 18.13 18.14 18.15 18.16 18.17 18.18 18.19 18.20 18.21 18.22 Aromatic Compounds 19.1 19.2 19.3 19.4 19.5 for Organic Chemistry Reactions of Benzene and Substituted Benzenes 910 ■ 19.8 SUMMARY OF REACTIONS 911 ■ PROBLEMS More About Amines • Reactions of Heterocyclic Compounds 913 924 More About Nomenclature 925 More About the Acid–Base Properties of Amines 926 MEDICAL CONNECTION: Atropine 927 Amines React as Bases and as Nucleophiles 927 Synthesis of Amines 929 Aromatic Five-Membered-Ring Heterocycles 929 931 P R O B L E M - S O LV I N G S T R AT E G Y 19.6 19.7 868 GENERAL CONNECTION: Measuring Toxicity 869 The Nomenclature of Monosubstituted Benzenes 870 GENERAL CONNECTION: The Toxicity of Benzene 871 The General Mechanism for Electrophilic Aromatic Substitution Reactions 871 Halogenation of Benzene 872 MEDICAL CONNECTION: Thyroxine 874 Nitration of Benzene 874 Sulfonation of Benzene 875 Friedel–Crafts Acylation of Benzene 876 Friedel–Crafts Alkylation of Benzene 877 CHEMICAL CONNECTION: Incipient Primary Carbocations 879 BIOLOGICAL CONNECTION: A Biological Friedel-Crafts Alkylation 879 Alkylation of Benzene by Acylation–Reduction 880 Using Coupling Reactions to Alkylate Benzene 881 How Some Substituents on a Benzene Ring Can Be Chemically Changed 882 The Nomenclature of Disubstituted and Polysubstituted Benzenes 884 The Effect of Substituents on Reactivity 886 The Effect of Substituents on Orientation 890 The Ortho–Para Ratio 894 Additional Considerations Regarding Substituent Effects 894 DESIGNING A SYNTHESIS VI: The Synthesis of Monosubstituted and Disubstituted Benzenes 896 The Synthesis of Trisubstituted Benzenes 898 Synthesizing Substituted Benzenes Using Arenediazonium Salts 900 Azobenzenes 903 HISTORICAL CONNECTION: Discovery of the First Antibiotic 904 PHARMACEUTICAL CONNECTION: Drug Safety 904 The Mechanism for the Formation of a Diazonium Ion 905 MEDICAL CONNECTION: A New Cancer-Fighting Drug 905 NUTRITIONAL CONNECTION: Nitrosamines and Cancer 906 Nucleophilic Aromatic Substitution 907 DESIGNING A SYNTHESIS VII: The Synthesis of Cyclic Compounds 909 ESSENTIAL CONCEPTS 19 867 Aromatic Six-Membered-Ring Heterocycles 934 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 Organizing What We Know About the Reactions of Organic Compounds (Group IV) 943 ESSENTIAL CONCEPTS 944 ■ SUMMARY OF REACTIONS 945 ■ PROBLEMS 946 MasteringChemistry tutorials guide you through the toughest topics in chemistry with self-paced tutorials that provide individualized coaching. These assignable, in-depth tutorials are designed to coach you with hints and feedback specific to your individual misconceptions. For additional practice on Synthesis and Retrosynthetic Analysis, go to MasteringChemistry where the following tutorials are available: • Synthesis and Retrosynthetic Analysis: Changing the Functional Group • Synthesis and Retrosynthetic Analysis: Disconnections • Synthesis and Retrosynthetic Analysis: Synthesis of Carbonyl Compounds xviii PART SEVEN 20 20.1 20.2 20.3 20.4 20.5 20.6 20.7 20.8 20.9 20.10 20.11 20.12 20.13 20.14 20.15 20.16 20.17 20.18 20.19 Bioorganic Compounds The Organic Chemistry of Carbohydrates 950 Classifying Carbohydrates 951 The d and l Notation 952 The Configurations of Aldoses 953 The Configurations of Ketoses 955 The Reactions of Monosaccharides in Basic Solutions 956 Oxidation–Reduction Reactions of Monosaccharides 957 Lengthening the Chain: The Kiliani–Fischer Synthesis 958 Shortening the Chain: The Wohl Degradation 959 MEDICAL CONNECTION: Measuring the Blood Glucose Levels in Diabetes 960 The Stereochemistry of Glucose: The Fischer Proof 960 GENERAL CONNECTION: Glucose/Dextrose 962 Monosaccharides Form Cyclic Hemiacetals 962 Glucose is the Most Stable Aldohexose 965 Formation of Glycosides 967 The Anomeric Effect 968 Reducing and Nonreducing Sugars 969 Disaccharides 969 NUTRITIONAL CONNECTION: Lactose Intolerance 971 MEDICAL CONNECTION: Galactosemia 971 BIOLOGICAL CONNECTION: A Toxic Disaccharide 972 Polysaccharides 973 MEDICAL CONNECTION: Why the Dentist is Right 974 BIOLOGICAL CONNECTION: Controlling Fleas 975 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 Carbohydrates on Cell Surfaces 978 Artificial Sweeteners 979 NUTRITIONAL CONNECTION: Acceptable Daily Intake 981 ESSENTIAL CONCEPTS New art adds clarity. 21 21.1 21.2 21.3 21.4 21.5 21.6 21.7 21.8 21.9 21.10 21.11 21.12 21.13 949 981 ■ SUMMARY OF REACTIONS Amino Acids, Peptides, and Proteins 982 ■ PROBLEMS 986 The Nomenclature of Amino Acids 987 NUTRITIONAL CONNECTION: Proteins and Nutrition 991 The Configuration of Amino Acids 991 MEDICAL CONNECTION: Amino Acids and Disease 992 PHARMACEUTICAL CONNECTION: A Peptide Antibiotic 992 Acid–Base Properties of Amino Acids 993 The Isoelectric Point 995 Separating Amino Acids 996 GENERAL CONNECTION: Water Softeners: Examples of Cation-Exchange Chromatography Synthesis of Amino Acids 1000 Resolution of Racemic Mixtures of Amino Acids 1002 Peptide Bonds and Disulfide Bonds 1003 MEDICAL CONNECTION: Diabetes 1006 CHEMICAL CONNECTION: Hair: Straight or Curly? 1006 Some Interesting Peptides 1006 The Strategy of Peptide Bond Synthesis: N-Protection and C-Activation 1007 Automated Peptide Synthesis 1010 An Introduction to Protein Structure 1013 BIOLOGICAL CONNECTION: Primary Structure and Taxonomic Relationship 1013 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 983 1000 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 22 22.1 22.2 22.3 22.4 22.5 22.6 22.7 22.8 22.9 22.10 22.11 22.12 22.13 23.1 23.2 23.3 23.4 23.5 23.6 23.7 23.8 24.1 24.2 24.3 24.4 24.5 24.6 PROBLEMS 1026 1030 Catalysis in Organic Reactions 1032 Acid Catalysis 1032 Base Catalysis 1035 Nucleophilic Catalysis 1037 Metal-Ion Catalysis 1038 Intramolecular Reactions 1040 Intramolecular Catalysis 1042 Catalysis in Biological Reactions 1044 An Enzyme-Catalyzed Reaction That Is Reminiscent of Acid-Catalyzed Amide Hydrolysis 1046 Another Enzyme-Catalyzed Reaction That Is Reminiscent of Acid-Catalyzed Amide Hydrolysis 1049 An Enzyme-Catalyzed Reaction That Involves Two Sequential SN2 Reactions 1052 MEDICAL CONNECTION: How Tamiflu Works 1055 An Enzyme-Catalyzed Reaction That Is Reminiscent of the Base-Catalyzed Enediol Rearrangement 1056 An Enzyme Catalyzed-Reaction That Is Reminiscent of a Retro-Aldol Addition 1057 1059 ■ PROBLEMS 1060 The Organic Chemistry of the Coenzymes, Compounds Derived from Vitamins 1063 HISTORICAL CONNECTION: Vitamin B1 1065 Niacin: The Vitamin Needed for Many Redox Reactions 1066 HISTORICAL CONNECTION: Niacin Deficiency 1067 Riboflavin: Another Vitamin Used in Redox Reactions 1071 Vitamin B1: The Vitamin Needed for Acyl Group Transfer 1075 GENERAL CONNECTION: Curing a Hangover with Vitamin B1 1078 Biotin: The Vitamin Needed for Carboxylation of an a-Carbon 1079 Vitamin B6: The Vitamin Needed for Amino Acid Transformations 1081 MEDICAL CONNECTION: Assessing the Damage After a Heart Attack 1085 Vitamin B12: The Vitamin Needed for Certain Isomerizations 1086 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 Vitamin K: The Vitamin Needed for Carboxylation of Glutamate 1093 MEDICAL CONNECTION: Anticoagulants 1095 NUTRITIONAL CONNECTION: Too Much Broccoli 1095 ESSENTIAL CONCEPTS 24 ■ Catalysis in Organic Reactions and in Enzymatic Reactions ESSENTIAL CONCEPTS 23 1025 1095 ■ PROBLEMS 1096 The Organic Chemistry of the Metabolic Pathways 1099 NUTRITIONAL CONNECTION: Differences in Metabolism 1100 ATP is Used for Phosphoryl Transfer Reactions 1100 CHEMICAL CONNECTION: Why Did Nature Choose Phosphates? 1102 Why ATP is Kinetically Stable in a Cell 1102 The “High-Energy” Character of Phosphoanhydride Bonds 1102 The Four Stages of Catabolism 1104 The Catabolism of Fats: Stages 1 and 2 1105 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 Increased emphasis on the connection between the reactions that occur in the laboratory and those that occur in cells. xx 24.7 24.8 24.9 24.10 24.11 24.12 24.13 24.14 NUTRITIONAL CONNECTION: Fats Versus Carbohydrates as a Source of Energy 1112 The Fate of Pyruvate 1112 The Catabolism of Proteins: Stages 1 and 2 1113 MEDICAL CONNECTION: Phenylketonuria (PKU): An Inborn Error of Metabolism 1114 MEDICAL CONNECTION: Alcaptonuria 1115 The Citric Acid Cycle: Stage 3 1115 Oxidative Phosphorylation: Stage 4 1118 NUTRITIONAL CONNECTION: Basal Metabolic Rate 1119 Anabolism 1119 Gluconeogenesis 1120 Regulating Metabolic Pathways 1122 Amino Acid Biosynthesis 1123 ESSENTIAL CONCEPTS The lipid material previously in the chapter on carboxylic acids and their derivatives has been moved into this new chapter. The discussion of terpenes from the metabolism chapter has also been moved into this chapter, along with some new material. 25 25.1 25.2 25.3 25.4 25.5 25.6 25.7 25.8 1124 ■ PROBLEMS The Organic Chemistry of Lipids 1125 1127 Fatty Acids Are Long-Chain Carboxylic Acids 1128 NUTRITIONAL CONNECTION: Omega Fatty Acids 1129 Waxes Are High-Molecular-Weight Esters 1130 Fats and Oils Are Triglycerides 1130 NUTRITIONAL CONNECTION: Olestra: Nonfat with Flavor 1132 BIOLOGICAL CONNECTION: Whales and Echolocation 1132 Soaps and Micelles 1132 Phospholipids Are Components of Cell Membranes 1134 BIOLOGICAL CONNECTION: Snake Venom 1136 MEDICAL CONNECTION: Multiple Sclerosis and the Myelin Sheath 1137 Prostaglandins Regulate Physiological Responses 1137 Terpenes Contain Carbon Atoms in Multiples of Five 1139 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 26 26.1 26.2 26.3 26.4 26.5 26.6 26.7 26.8 26.9 26.10 26.11 26.12 26.13 1151 ■ PROBLEMS The Chemistry of the Nucleic Acids 1152 1155 Nucleosides and Nucleotides 1155 HISTORICAL CONNECTION: The Structure of DNA: Watson, Crick, Franklin, and Wilkins 1158 BIOLOGICAL CONNECTION: Cyclic AMP 1159 Nucleic Acids Are Composed of Nucleotide Subunits 1159 The Secondary Structure of DNA 1161 Why DNA Does Not Have A 2′-OH Group 1163 The Biosynthesis of DNA Is Called Replication 1163 DNA and Heredity 1164 PHARMACEUTICAL CONNECTION: Natural Products That Modify DNA 1165 The Biosynthesis of RNA Is Called Transcription 1165 BIOLOGICAL CONNECTION: There Are More Than Four Bases in DNA 1166 The RNAs Used for Protein Biosynthesis 1167 The Biosynthesis of Proteins Is Called Translation 1169 MEDICAL CONNECTION: Sickle Cell Anemia 1171 MEDICAL CONNECTION: Antibiotics That Act by Inhibiting Translation 1172 Why DNA Contains Thymine Instead of Uracil 1173 MEDICAL CONNECTION: Antibiotics Act by a Common Mechanism 1174 Antiviral Drugs 1174 HISTORICAL CONNECTION: Influenza Pandemics 1175 How the Base Sequence of DNA Is Determined 1175 Genetic Engineering 1177 xxi ENVIRONMENTAL CONNECTION: Resisting Herbicides 1177 PHARMACEUTICAL CONNECTION: Using Genetic Engineering to Treat the Ebola Virus 1177 ESSENTIAL CONCEPTS 27.1 27.2 27.3 27.4 27.5 27.6 27.7 27.8 27.9 27.10 27.11 27.12 27.13 27.14 Synthetic Polymers 28 28.7 PROBLEMS 1178 1181 1182 There Are Two Major Classes of Synthetic Polymers 1183 An Introduction To Chain-Growth Polymers 1184 Radical Polymerization 1184 INDUSTRIAL CONNECTION: Teflon: An Accidental Discovery 1187 ENVIRONMENTAL CONNECTION: Recycling Symbols 1189 Cationic Polymerization 1189 Anionic Polymerization 1192 Ring-Opening Polymerizations 1193 Stereochemistry of Polymerization • Ziegler–Natta Catalysts 1195 Polymerization of Dienes 1196 Copolymers 1198 PHARMACEUTICAL CONNECTION: Nanocontainers 1198 An Introduction to Step-Growth Polymers 1199 Classes of Step-Growth Polymers 1200 MEDICAL CONNECTION: Health Concerns: Bisphenol A and Phthalates 1202 INDUSTRIAL CONNECTION: Designing a Polymer 1203 Physical Properties of Polymers 1204 NUTRITIONAL CONNECTION: Melamine Poisoning 1205 Recycling Polymers 1206 Biodegradable Polymers 1207 ESSENTIAL CONCEPTS 28.1 28.2 28.3 28.4 28.5 28.6 ■ Special Topics in Organic Chemistry PART EIGHT 27 1178 1208 Pericyclic Reactions ■ PROBLEMS 1208 1212 There Are Three Kinds of Pericyclic Reactions 1213 Molecular Orbitals and Orbital Symmetry 1215 Electrocyclic Reactions 1218 Cycloaddition Reactions 1224 Sigmatropic Rearrangements 1227 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 Summary of the Selection Rules for Pericyclic Reactions 1235 ESSENTIAL CONCEPTS Appendices I 1236 ■ PROBLEMS 1236 A-1 PKA VALUES II KINETICS A-1 A-3 III SUMMARY OF METHODS USED TO SYNTHESIZE A PARTICULAR FUNCTIONAL GROUP IV SUMMARY OF METHODS EMPLOYED TO FORM CARBON-CARBON BONDS V SPECTROSCOPY TABLES A-12 VI PHYSICAL PROPERTIES OF ORGANIC COMPOUNDS ANSWERS TO SELECTED PROBLEMS GLOSSARY CREDITS INDEX I-1 G-1 C-1 ANS-1 A-18 A-11 A-8 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. • Group IV: Aromatic compounds. Some aromatic compounds are nucleophiles and, therefore, react with electrophiles—undergoing electrophilic aromatic substitution reactions. Other aromatic compounds are electrophiles and, therefore, react with nucleophiles—undergoing nucleophilic aromatic substitution reactions. The organization discourages rote memorization and allows students to learn reactions based on their pattern of reactivity. It is only after these patterns of reactivity are understood that a deep understanding of organic chemistry can begin. As a result, students achieve the predictive capacity that is the beauty of studying science. A course that teaches students to analyze, classify, explain, and predict gives them a strong foundation to bring to their subsequent study of science, regardless of the discipline. As students proceed through the book, they come across ~200 interest boxes that connect what they are studying to real life. Students don’t have to be preparing for a career in medicine to appreciate a box on the experimental drug used to treat Ebola, and they don’t have to be preparing for a career in engineering to appreciate a box on the properties that a polymer used for dental impressions must have. xxii Preface xxiii The Organization Ties Together Reactivity and Synthesis Many organic chemistry textbooks discuss the synthesis of a functional group and the reactivity of that group sequentially, but these two groups of reactions generally have little to do with one another. Instead, when I discuss a functional group’s reactivity, I cover the synthesis of compounds that are formed as a result of that reactivity, often by having students design syntheses. In Chapter 6, for example, students learn about the reactions of alkenes, but they do not learn about the synthesis of alkenes. Instead, they learn about the synthesis of alkyl halides, alcohols, ethers, epoxides, alkanes, etc.—the compounds formed when alkenes react. The synthesis of alkenes is not covered until the reactions of alkyl halides and alcohols are discussed—compounds whose reactions lead to the synthesis of alkenes. This strategy of tying together the reactivity of a functional group and the synthesis of c ompounds resulting from its reactivity prevents the student from having to memorize lists of unrelated reactions. It also results in a certain economy of presentation, allowing more material to be covered in less time. Although memorizing different ways a particular functional group can be prepared can be counterproductive to enjoying organic chemistry, it is useful to have such a compilation of reactions when designing multistep syntheses. For this reason, lists of reactions that yield a particular functional group are compiled in Appendix III. In the course of learning how to design syntheses, students come to appreciate the importance of reactions that change the carbon skeleton of a molecule; these reactions are compiled in Appendix IV. Helping Students Learn and Study Organic Chemistry As each student generation evolves and becomes increasingly diverse, we are challenged as teachers to support the unique ways students acquire knowledge, study, practice, and master a subject. In order to support contemporary students who are often visual learners, with preferences for interactivity and small “bites” of information, I have revisited this edition to make it more compatible with their learning style by streamlining the narrative and using organizing bullets and subheads. This will allow them to study more efficiently with the text. The book is written much like a tutorial. Each section ends with a set of problems that students need to work through to find out if they are ready to go on to the next section, or if they need to review the section they thought they had just mastered. This allows the book to work well in a “flipped classroom.” For those who teach organic chemistry after one semester of general chemistry, Chapter 5 and Appendix II contain material on thermodynamics and kinetics, so those topics can be taught in the organic course. An enhanced art program with new and expanded annotations provides key information to students so that they can review important parts of the chapter with the support of the visual program. Margin notes throughout the book succinctly repeat key points and help students review important material at a glance. Tutorials follow relevant chapters to help students master essential skills: • Acids and Bases • Using Molecular Models • Interconverting Structural Representations • Drawing Curved Arrows • Drawing Resonance Contributors • Drawing Curved Arrows in Radical Systems • Synthesis and Retrosynthetic analysis MasteringChemistry includes additional online tutorials on each of these topics that can be assigned as homework or for test preparation. Organizational Changes Using the E,Z system to distinguish alkene stereoisomers was moved to Chapter 4, so now it appears immediately after using cis and trans to distinguish alkene stereoisomers. Catalytic hydrogenation and the relative stabilities of alkenes was moved from Chapter 6 to Chapter 5 (thermodynamics), so it can be used to illustrate how ΔH° values can be used to determine relative stabilities. Moving this has another advantage—because catalytic hydrogenation is the only reaction of alkenes that does not have a well-defined mechanism, all the remaining reactions xxiv 308 Preface CH APT E R 7 The Reactions of Alkynes • An Introduction to Multistep Synthesis in Chapter 6 now have well-defined mechanisms, all following the general rule that applies to all Designing a Synthesis 2 NOTE TO THE STUDENT • As the number of reactions that you know increases, you may find it helpful to consult Appendix III when designing syntheses; it lists the methods that can be used to synthesize each functional group. electrophilic addition reactions: the first step is always the addition of the electrophile to the sp The following willhydrogens. give you an idea of the type of thinking required to design a successful carbon bondedexamples to the most synthesis. Problems of this kind repeatedly throughout because solvingto them Chapter 8 starts by discussingwill theappear structure of benzene becausethe it isbook, the ideal compound use is fun and is a good way to learn organic chemistry. to explain delocalized electrons. This chapter also includes a discussion on aromaticity, so a short introduction to electrophilic aromatic substitution reactions is now included. This allows students Example 1 to see how aromaticity causes benzene to undergo electrophilic substitution rather than electrophilic addition—the reactions they justyou finished Starting with 1-butyne, how could makestudying. the ketone shown here? You can use any reagents you need. Traditionally, electronic effects are taught so students can O understand the activating and directing effects of substituents on benzene rings. Now? that most of the chemistry of benzene follows carCH3CH2C CH CH3CH2CCH2CH2CH3 bonyl chemistry, students need to know about electronic effects before they get to benzene chemistry (so they are better prepared1-butyne for spectroscopy and carbonyl chemistry). Therefore, in this edition electronic effects arethat discussed in Chapter 8 and used to teachis students how substituents the Many chemists find the easiest way to design a synthesis to work backward. Insteadaffect of lookvalues of phenols, anilinium effects look are then reviewed the pKaat ing the reactant and benzoic decidingacids, how and to do the firstions. step Electronic of the synthesis, at the productinand chapterhow on benzene. decide to do the last step. The product two chapters the previous covered the substitution reactions of The of theinsynthesis is a edition ketone.that Now you need to rememberand all elimination the reactions you have alkyl halides have abeen combined into (Chapter addition 9). The recent compelling evidence learned that form ketone. We will useone thechapter acid-catalyzed of water to an alkyne. (Youshowalso 1 solvolysis reactions allowed material to be greatly ing that halides do not undergo S could usealkyl hydroboration–oxidation.) IfNthe alkyne used in the has reaction hasthis identical substituents on simplified, so now it fits into one both sp carbons, only onenicely ketone will bechapter. obtained. Thus, 3-hexyne is the alkyne that should be used have found that teaching for Ithe synthesis of the desiredcarbonyl ketone. chemistry before the chemistry of aromatic compounds (a change made in the last edition) has worked well for my students. Carbonyl compounds are probO OH ably the most important organic compounds, and moving them forward gives them the prominence H2O CH3CHhave. CH3location CH2C CHCH CHbenzene they should In addition, the current of the2CH chemistry of allows it 3and the 2C CCH 2CH3 3 3CH2CCH 2CH2CH H2SO4 chemistry of 3-hexyne aromatic heterocyclic compounds to be taught sequentially. The focus of the first chapter on carbonyl chemistry should be all about how a tetrahedral inter3-Hexyne can be obtained from the starting material (1-butyne) by removing the proton from its mediate partitions. If students understand this, then carbonyl chemistry becomes relatively easy. I sp carbon, followed by alkylation. To produce the desired six-carbon product, a two-carbon alkyl found that the lipid material that had been put into this chapter detracted from the main message halide must be used in the alkylation reaction. of the chapter. Therefore, the lipid material was removed and put into a new chapter: The Organic 1. NaNH2from the metabolism chapter has also been moved Chemistry of Lipids. The CH3discussion CH2C CHof terpenes CH3CH2C CCH2CH3 2. CH3CH2Br into this chapter, and some1-butyne some new material has been included. 3-hexyne Designing a synthesis by working backward from product to reactant is not just a technique Modularity/Spectroscopy taught to organic chemistry students. It is used so frequently by experienced synthetic chemists that itThe has book been given a name: retrosynthetic use open arrows when they write is designed to be modular,analysis. so the Chemists four groups (Group I—Chapters 6, 7,ret8; rosynthetic analyses to indicate they are working backward. Typically, the reagents needed carry Group II—Chapters 9 and 10; Group III—Chapters 15, 16, 17; Group IV—Chapters 18 andto 19) can out each stepinare specified until the reaction is written in the forward direction. For example, the be covered anynot order. ketone just discussed arrived at by the following retrosynthetic Sixtysynthesis spectroscopy problemsis and their answers—in addition to ~170 analysis. spectroscopy problems in the text—can be found in the Study Guide and Solutions Manual. The spectroscopy chapters retrosynthetic analysis (Chapters 13 and 14) are written so that they can be covered at any time during the course. For those O to teach spectroscopy before all the functional groups have been introduced—or in a who prefer separate laboratory course—there is 2aCtable of2CH functional groups the beginning of Chapter 13. CH CH3CH CCH CH3CHat 3CH2CCH2CH2CH3 3 2C CH Once the sequence of reactions is worked out by retrosynthetic analysis, the synthetic scheme can An Early and Consistent Emphasis on Organic Synthesis be written by reversing the steps and including the reagents required for each step. Students are introduced to synthetic chemistry and retrosynthetic analysis early in the book synthesis (Chapters 6 and 7, respectively), so they can start designing multistep syntheses early in the course. O are introduced at appropriSeven special sections on synthesis design, each with a different focus, 1. NaNH Hretrosynthetic 2 2O ate intervals. There is also a tutorial on synthesis and analysis that includes some CH3CH2C CH 2. CH CH Br CH3CH2C CCH2CH3 H SO CH3CH2CCH 2CH2CH3 3 2multistep syntheses from the literature. 2 4 examples of complicated Example 2 Starting with ethyne, how could you make 2-bromopentane? HC CH ethyne ? CH3CH2CH2CHCH3 Br 2-bromopentane 2-Bromopentane can be prepared from 1-pentene, which can be prepared from 1-pentyne. 1-Pentyne can be prepared from ethyne and an alkyl halide with three carbons. Preface xxv Problems, Solved Problems, and Problem-Solving Strategies The book contains more than 2,000 problems, many with multiple parts. This edition has many new problems, both in-chapter and end-of-chapter. They include new solved problems, new problemsolving strategies, and new problems incorporating information from more than one chapter. I keep a list of questions my students have when they come to office hours. Many of the new problems were created as a result of these questions. The answers (and explanations, when needed) to all the problems are in the accompanying Study Guide/Solutions Manual, which I authored to ensure consistency in language with the text. The problems within each chapter are primarily drill problems. They appear at the end of each section, so they allow students to test themselves on material just covered before moving on to the next section. Short answers provided at the end of the book for problems marked with a diamond give students immediate feedback concerning their mastery of a skill or concept. Selected problems are accompanied by worked-out solutions to provide insight into problemsolving techniques, and the many Problem-Solving Strategies teach students how to approach various kinds of problems. These skill-teaching problems are indicated by LEARN THE STRATEGY in the margin. These strategies are followed by one or more problems that give students the opportunity to use the strategy just learned. These problems, or the first of a group of such problems, are indicated in the margin by USE THE STRATEGY. The Study Guide/Solutions Manual has a practice test at the end of each chapter and contains Special Topics Sections on molecular orbital theory and how to solve problems on pH, pKa, and buffer solutions. Powerpoint All the art in the text is available on PowerPoint slides. I created the PowerPoint lectures so they would be consistent with the language and philosophy of the text. Students Interested in The Biological Sciences and Mcat2015 I have long believed that students who take organic chemistry also should be exposed to bioorganic chemistry—the organic chemistry that occurs in biological systems. Students leave their organic chemistry course with a solid appreciation of organic mechanism and synthesis. But when they take biochemistry, they will never hear about Claisen condensations, SN2 reactions, nucleophilic acyl substitution reactions, etc., although these are extremely important reactions in cells. Why are students required to take organic chemistry if they are not going to be taught how the organic chemistry they learn repeats itself in the biological world? Now that the MCAT is focusing almost exclusively on the organic chemistry of living systems, it is even more important that we provide our students with the “bioorganic bridge”—the material that provides the bridge between organic chemistry and biochemistry. Students should see that the organic reactions that chemists carry out in the laboratory are in many ways the same as those performed by nature inside a cell. The seven chapters (Chapters 20–26) that focus primarily on the organic chemistry of living systems emphasize the connection between the organic reactions that occur in the laboratory and those that occur in cells. Each organic reaction that occurs in a cell is explicitly compared to the organic reaction with which the student is already familiar. For example, the first step in glycolysis is an SN2 reaction, the second step is identical to the enediol rearrangement that students learn when they study carbohydrate chemistry, the third step is another SN2 reaction, the fourth step is a reverse aldol addition, and so on. The first step in the citric acid cycle is an aldol addition followed by a nucleophilic acyl substitution reaction, the second step is an E2 dehydration followed by the conjugate addition of water, the third step is oxidation of a secondary alcohol followed by decarboxylation of a 3-oxocarboxylate ion, and so on. We teach students about halide and sulfonate leaving groups. Adding phosphate leaving groups takes little additional time but introduces the students to valuable information if they are going on to study biochemistry. xxvi Preface Students who study organic chemistry learn about tautomerization and imine hydrolysis, and students who study biochemistry learn that DNA has thymine bases in place of the uracil bases in RNA. But how many of these students are ever told that the reason for the difference in the bases in DNA and RNA is tautomerization and imine hydrolysis? Colleagues have asked how they can find time to fit the “bioorganic bridge” into their organic chemistry courses. I found that tying together reactivity and synthesis (see p. xxiii) frees up a lot of time. (This is the organization I adopted many years ago when I was trying to figure out how to incorporate the bioorganic bridge into my course.) And if you find that this still does not give you enough time, I have organized the book in a way that allows some “traditional” chapters to be omitted (Chapters 12, 18, 19, and 28), so students can be prepared for biochemistry and/or the MCAT without sacrificing the rigor of the organic course. The Bioorganic Bridge Bioorganic chemistry is found throughout the text to show students that organic chemistry and biochemistry are not separate entities but rather are closely related on a continuum of knowledge. Once students learn how, for example, electron delocalization, leaving-group propensity, electrophilicity, and nucleophilicity affect the reactions of simple organic compounds, they can appreciate how these same factors influence the reactions of organic compounds in cells. In Chapters 1–19, the bioorganic material is limited mostly to “interest boxes” and to the last sections of the chapters. Thus, the material is available to the curious student without requiring the instructor to introduce bioorganic topics into the course. For example, after hydrogen bonding is introduced in Chapter 3, hydrogen boding in proteins in DNA is discussed; after catalysis is introduced in Chapter 5, catalysis by enzymes is discussed; after the stereochemistry of organic reactions is presented in Chapter 6, the stereochemistry of enzyme-catalyzed reactions is discussed; after sulfonium ions are discussed in Chapter 10, a biological methylation reaction using a sulfonium ion is examined and the reason for the use of different methylating agents by chemists and cells is explained; after the methods chemists use to activate carboxylic acids are presented (by giving them halide or anhydride leaving groups) in Chapter 15, the methods cells use to activate these same acids are explained (by giving them phosphoanhydride, pyrophosphate, or thiol leaving groups); and after condensation reactions are discussed in Chapter 17, the mechanisms of some biological condensation reactions are shown. In addition, seven chapters in the last part of the book (Chapters 20–26) focus on the organic chemistry of living systems. These chapters have the unique distinction of containing more chemistry than is typically found in the corresponding parts of a biochemistry text. Chapter 22 (Catalysis in Organic Reactions and in Enzymatic Reactions), for example, explains the various modes of catalysis employed in organic reactions and then shows that they are identical to the modes of catalysis found in reactions catalyzed by enzymes. All of this is presented in a way that allows students to understand the lightning-fast rates of enzymatic reactions. Chapter 23 (The Organic Chemistry of the Coenzymes, Compounds Derived from Vitamins) emphasizes the role of vitamin B1 in electron delocalization, vitamin K as a strong base, vitamin B12 as a radical initiator, biotin as a compound that transfers a carboxyl group by means of a nucleophilic acyl substitution reaction, and describes how the many different reactions of vitamin B6 have common mechanisms—with the first step always being imine formation. Chapter 24 (The Organic Chemistry of Metabolic Pathways) explains the chemical function of ATP and shows students that the reactions encountered in metabolism are just additional examples of reactions that they already have mastered. In Chapter 26 (The Chemistry of the Nucleic Acids), students learn that 2′-OH group on the ribose molecules in RNA catalyzes its hydrolysis and that is why DNA, which has to stay intact for the life of the cell, does not have 2′-OH groups. Students also see that the synthesis of proteins in cells is just another example of a nucleophilic acyl substitution reaction. Thus, these chapters do not replicate what will be covered in a biochemistry course; they provide a bridge between the two disciplines, allowing students to see how the organic chemistry that they have learned is repeated in the biological world. HN O + N5,N10-methylene-THF synthase HN O N + dihydrofolate N 2 -deoxyribose-5-P Because the incorporation of the methyl group into uracil oxidizes tetrahydrofolate to dihydrofolate, dihydrofolate must be reduced back to tetrahydrofolate to prepare the coenzyme for another catalytic reaction. The reducing agent is NADPH. ENGAGING MIXED SCIENCE MAJORS IN ORGANIC CHEMISTRY 26.13better GENETIC ENGINEERING Students understand the relevance of what they’re 26.13 Genetic Engineering 1177 + dihydrofolate + NADPH + H dihydrofolate reductase tetrahydrofolate + NADP+ The NADP+ formed in this reaction has to be reduced back to NADPH by NADH. Every NADH Genetic engineering (also called modification) is the insertion a segment of DNAformed into in a cell can result in the formation of 2.5 ATPs (Section 24.10). Therefore, reducing dihystudying by seeing the genetic connections between the ofreactions the DNA of a host cell so that the segment of DNA is replicated by the DNA-synthesizing machindrofolate comes at the expense of ATP. This means that the synthesis of thymine is energetically of that occur in the laboratory those replicating ery organic of the host compounds cell. Genetic engineering has many practical applications.and For example, expensive, so there must be a good reason for DNA to contain thymine instead of uracil. the DNA that codes human insulin makes it possible tothis synthesize largeprovide amounts of the protein, that occur in a for cell. Changes throughout edition The presence of thymine instead of uracil in DNA prevents potentially lethal mutations. Cytosine eliminating the dependence on pigs for insulin and helping those who are allergic to pig insulin. students with this much-needed “bioorganic bridge,” can tautomerize to form an imine (Section 17.2), which can be hydrolyzed to uracil (Section 16.8). Recall that pig insulin differs from human insulin by one amino acid (Section while 21.8). Agriculture is benefiting from engineering. Crops are now being produced withThe newoverall reaction is called a deamination because it removes an amino group. maintaining the rigor ofgenetic the traditional organic course. genes that increase their resistance to drought and insects. For example, genetically engineered For example, students about halide and cotton crops are resistant we to theteach cotton bollworm, and genetically engineered cornsulis resistant to the deamination corn rootworm. Genetically modified organismsphosphate (GMOs) have leaving been responsible for a nearly 50% fonate leaving groups. Adding groups NH2 NH O reduction in the use of chemicals for agricultural purposes in the United States. Recently, corn has takes little additional time, but it introduces students to been genetically modified to boost ethanol production, apples have been genetically modified to tautomerization H2O HN HN N + NH3 prevent theminformation, from turning brown when they are cut, and soybeans have been genetically modified valuable particularly if they are taking organic to prevent trans fats from being formed when soybean oil is hydrogenated (Section 5.9). O O O N N N chemistry because of an interest in the biological sciences. H H H Students who are studying organic chemistry learn about uracil cytosine imino tautomer amino tautomer Resisting Herbicides tautomerization and imine hydrolysis, and students studyGlyphosate, the active ingredient in a well-known herbicide called Roundup, kills weeds by inhibIf a C in DNA is deaminated to a U, the U will specify incorporation of an A into the daughter ing biochemistry learn that DNA has thymine bases in place iting an enzyme that plants need to synthesize phenylalanine and tryptophan, amino acids they strand during replication instead of the G that would have been specified by C, and all the progeny ofrequire the uracil bases Butbeen how manyengineered of these students for growth. Corn in and RNA. cotton have genetically to tolerate the herbicide. of the daughter strand would have the same mutated chromosome. Fortunately, there is an enzyme Then, when fields are sprayed with glyphosate, the weeds are killed but not the crops. are ever told that the reason for the difference in the bases that recognizes a U in DNA as a “mistake” and replaces it with a C before an incorrect base can be These crops have been given a gene that produces an enzyme that uses acetyl-CoA to acetyin late DNA and inRNA is tautomerization and(Section imine15.11 hydrolysis? inserted into the daughter strand. The enzyme cuts out the U and replaces it with a C. If Us were glyphosate a nucleophilic acyl substitution reaction ). Unlike glyphosphate, N-acetylglyphosphate does not inhibit the enzyme that synthesizes phenylalanine and tryptophan. normally found in DNA, the enzyme would not be able to distinguish between a normal U and a U formed by deamination of a cytosine. Having Ts in place of Us in DNA allows the Us that are found in DNA to be recognized as mistakes. CH O More Applications Than Any Other Organic Text O O O O C O 3 enzyme C and NH Updated P + Application C C NthePdiscussion + CoASH NEW! boxes connect to medical, environmental, biologi− − O O− SCoA O O− CH3 genetically engineered to resist the herbicide O− cal, pharmaceutical, nutritional, chemical, industrial,O−historical, andcorn general applications and allow glyphosate by acetylating it glyphosate acetyl-CoA N-acetylglyphosate students to relate the material to real life andharmless to potential future careers. an herbicide to plants 392 CHAPTER 9 Substitution and Elimination Reactions of Alkyl Halides Using Genetic Engineering to Treat the Ebola Virus This chapter focuses on the substitution and elimination reactions of alkyl halides—compounds - - - - , Br ,10.9 or I).). in which the leaving groupare is ajust halide (F , Cl Plants have long been a source of drugs—morphine, ephedrine, and codeine a fewion examples (Section Now scientists are attempting to obtain drugs from plants by biopharming. Biopharming uses genetic engineering techniques to produce drugs in crops such as corn, rice, tomatoes, and tobacco. To date, the only biopharmed alkyl halides drug approved by the Food and Drug Administration (FDA) is one that is manufactured in carrots and used to treat GauR F R Cl R Br R I cher’s disease. fluoride alkyl chloride bromide alkyl iodide An experimental drug that was used to treat a handful alkyl of patients with Ebola, the virus that was alkyl spreading throughout West Africa, was obtained from genetically engineered tobacco plants. The tobacco plants Alkyl halides arethat a good of to compounds withanimals which to start the study of substitution and were infected with three genetically engineered plant viruses are family harmless humans and elimination reactions have relatively leaving groups; that is, the halide ions are but have structures similar to that of the Ebola virus. As a resultbecause of beingthey infected, the plantsgood produced easily displaced. After learning aboutand the then reactions halides, you will be prepared to move on antibodies to the viruses. The antibodies were isolated from the plants, purified, used of to alkyl treat the to Chapter 10, which discusses the substitution and elimination reactions of compounds with poorer patients with Ebola. leaving groupswho (those areexposed more difficult to displace) as well as a few with better leaving groups. The experimental drug had been tested in 18 monkeys hadthat been to a lethal dose of Ebola. Substitution elimination reactions are drugs important in organic chemistry because they make it All 18 monkeys survived, whereas the three monkeys in theand control group died. Typically, go through to convert to readily available alkyl into. aInwide rigorous testing on healthy humans prior to possible being administered infected patients (seehalides page 290) the variety of other compounds. These reactions are also in thebecells of patients’ plants and animals. Ebola case, the FDA made an exception because it feared that important the drug might these only hope. We will see, however, that because cells Currently, exist in predominantly environments alkyl Five of the seven people given the drug survived. it takes about aqueous 50 kilograms of tobaccoand leaves andhalides are insoluble in water, biologitobacco compounds in which the group that is replaced is more polar thanplants a halogen and, about 4 to 6 months to produce enough drugcal to systems treat oneuse patient. therefore, more water soluble (Section 10.12). The Birth of the Environmental Movement Alkyl halides have been used as insecticides since 1939, when it was discovered that DDT (first synthesized in 1874) has a high toxicity to insects and a relatively low toxicity to mammals. DDT was used widely in World War II to control typhus and malaria in both the military and civilian populations. It saved millions of lives, but no one realized at that time that, because it is a very stable compound, it is resistant to biodegradation. In addition, DDT and DDE, a compound formed as a result of elimination of HCl from DDT, are not water soluble. Therefore, they accumulate in the fatty tissues of birds and fish and can be passed up the food chain. Most older adults have a low concentration of DDT or DDE in their bodies. In 1962, Rachel Carson, a marine biologist, published Silent Spring, where she pointed out the environmental impacts of the widespread use of DDT. The book was widely read, so it brought the problem of environmental pollution to the attention of the general public for the first time. Consequently, its publication was an important event in the birth of the environmental movement. Because of the concern it raised, DDT was banned in the United States in 1972. In 2004, the Stockholm Convention banned the worldwide use of DDT except for the control of malaria in countries where the disease is a major health problem. In Section 12.12, we will look at the environmental effects caused by synthetic alkyl halides known as chlorofluorohydrocarbons (CFCs). Cl Cl Cl Cl DDT Cl xxvii PROBLEM 1 PROBLEM 2 Methoxychlor is an insecticide that was intended to take DDT’s place because it is not as soluble in fatty tissues and is more readily biodegradable. It, too, can accumulate in the environment, however, so its use xxviii Preface GUIDED APPROACH TO PROBLEM SOLVING ESSENTIAL SKILL DRAWING CURVED ARROWS Essential Skill Tutorials TUTORIAL This is an extension of what you learned about drawing curved arrows on pp. 199–201. Working through these problems will take only a little of your time. It will be time well spent, however, because curved arrows are used throughout the book and it is important that you are comfortable with them. (You will not encounter some of the reaction steps shown in this exercise for weeks or even months, so don’t worry about why the chemical changes take place.) These tutorials guide students through some of the topics in organic chemistry that they typically find to be the most c hallenging. They provide concise explanations, related problem-solving opportunities, and answers for self-check. The print tutorials are paired with MasteringChemistry online tutorials. These are additional problem sets that can be assigned as h omework or as test preparation. TUTORIAL ESSENTIAL SKILL Enhanced by Chemists use curved arrows to show how electrons move as covalent bonds break and/or new covalent bonds form. ■ Each arrow represents the simultaneous movement of two electrons (an electron pair) from a nucleophile (at the tail of the arrow) toward an electrophile (at the point of the arrow). ■ The tail of the arrow is positioned where the electrons are in the reactant; the tail always starts at a lone pair or at a bond. ■ The head of the arrow points to where these same electrons end up in the product; the arrow always points at an atom or at a bond. In the following reaction step, the bond between bromine and a carbon of the cyclohexane ring breaks and both electrons in the bond end up with bromine. Thus, the arrow starts at the electrons that carbon and bromine share in the reactant, and the head of the arrow points at bromine because this is where the two electrons end up in the product. Br − + + Br Notice that the carbon of the cyclohexane ring is positively charged in the product. This is because it has lost the two electrons it was sharing with bromine. The bromine is negatively charged in the product because it has gained the electrons that it shared with carbon in the reactant. The fact that two electrons move in this example is indicated by the two barbs on the arrowhead. Notice that the arrow always starts at a bond or at a lone pair. It does not start at a negative charge. + CH3CHCH3 + Cl − CH3CHCH3 Cl In the following reaction step, a bond is being formed between the oxygen of water and a carbon of the other reactant. The arrow starts at one of the lone pairs of the oxygen and points at the atom (the carbon) that will share the electrons in the product. The oxygen in the product is positively charged, because the electrons that oxygen had to itself in the reactant are now being shared with carbon. The carbon that was positively charged in the reactant is not charged in the product, because it has gained a share in a pair of electrons. + CH3CHCH3 19.8 + CH3CHCH3 H2O Organizing What We Know about the Reactions of Organic Compounds OH + H Draw curved arrows to show the movement of the electrons in the following reaction steps. (The answers to all problems appear immediately after Problem 10.) Porphyrin, Bilirubin, and Jaundice PROBLEM 1 CH3 CH3 + Br CH CHday. C Br The protein CH CH C The average human body breaks down about 6 g of hemoglobin a.each portion (globin) and the iron are CH CH reutilized, but the porphyrin ring is cleaved between the A and B rings to form a linear tetrapyrrole called biliverdin + Cl forming bilirubin (a red-orange (a green compound). Then the bridge between the C and b.D ringCl is reduced, compound). You can witness heme degradation by observing the changing colors of a bruise. Enzymes in the large intestine reduce bilirubin to urobilinogen (a colorless compound). Some urobilinogen is transported to the kidney, where it is oxidized to urobilin (a yellow compound). This is the compound that gives urine its characteristic color. If more bilirubin is formed than can be metabolized and excreted by the liver, it accumulates in the blood. When its concentration there reaches a certain level, it diffuses into the tissues, giving them a yellow appearance. This condition is known as jaundice. 3 2 3 3 2 − + 3 + − 225 Organizing What We Know About the Reactivity of Organic Compounds This organization emphasizes the unifying principles of reactivity and offers an economy of presentation while discouraging memorization. Students learn that • organic compounds can be classified into families and that all members of a family react in the same way. • the families can be put into one of four groups and that all the family members in a group react in similar ways. The Organizing What We Know table builds as students work sequentially through the four groups. Group I: electrophilic addition reactions Group II: nucleophilic substitution reactions and elimination reactions Group III: nucleophilic acyl substitution reactions, nucleophilic addition reactions, and nucleophilic addition–elimination reactions Group IV: electrophilic (and nucleophilic) aromatic substitution reactions ORGANIZING WHAT WE KNOW ABOUT THE REACTIONS OF ORGANIC COMPOUNDS 19.8 Group I R CH CH Group II R R C C R R CH O R OH alcohol alkyne R X alkyl halide alkene R Group III X = F, Cl, Br, I CH CH CH R R ether diene + N R R HO R R quaternary ammonium hydroxide epoxide O R O R − O These are nucleophiles. They undergo electrophilic addition reactions. R R S R R O sulfonium salt sulfonate ester S+ R These are electrophiles. They undergo nucleophilic substitution and/or elimination reactions. Z Z = an atom more electronegative than C benzene O R OR C Group IV C Z Z = C or H These are electrophiles. They undergo nucleophilic acyl substitution reactions, nucleophilic addition reactions, or nucleophilic addition–elimination reactions. Removal of a hydrogen from an A-carbon forms a nucleophile that can react with electrophiles. N pyridine Z = N, O, or S H pyrrole, furan, thiophene Z These are nucleophiles. They undergo electrophilic aromatic substitution reactions. Halo-substituted benzenes and halo-substituted pyridines are electrophiles. They undergo nucleophilic aromatic substitution reactions. We saw that the families of organic compounds can be put in one of four groups, and that all the families in a group react in similar ways. Now that we have finished studying the families in Group IV, let’s review how these compounds react. All the compounds in Group IV are aromatic. To preserve the aromaticity of the rings, these 696 CH APTER 15 Reactions of Carboxylic Acids and Carboxylic Acid Derivatives acyl substitution reaction is the p bond, so this bond breaks first and the leaving group is eliminated in a subsequent step. Preface xxix − Y + Z CH3CH2 Emphasis on the Strategies Needed to Solve Problems and Master Content Z + Y CH3CH2 − an SN2 reaction Passages explaining important problem-solving PROBLEM-SOLVING STRATEGY strategies are clearly labeled with a LEARN THE THE STRATEGY Using Basicity to Predict the Outcome of a Nucleophilic Acyl Substitution Reaction 836 C HA P T E RLEARN 1 7 Reactions at the a-Carbon STRATEGY label. Follow-up problems that require What is the product of the reaction of acetyl chloride with CH3O-? The pKa of HCl is –7; the pKa of CH3OH is 15.5. students to apply the just-learned strategy are P R O B L E M 4 2 S O LV E D To identify the product of the reaction, we need to compare the basicities of the two groups in the tetralabeled with a USE THE STRATEGY label. These Starting with methyl propanoate, how could you prepare 4-methyl-3-heptanone? hedral intermediate so we can determine which one will be eliminated. Because HCl is a stronger acid than labels, which are implemented throughout the text, O CH3O−. Therefore, Cl− isOeliminated from the tetrahedral intermediate CH3OH, Cl− is a weaker base than ? and methyl acetate is the productCof the reaction. allow students to easily find important content and C CH3CH2 CH3CH2 OCH3 CHCH2CH2CH3 practice its use. O O O− methyl propanoate CH C + CH3O− Cl CH3 C CH3 C 4-methyl-3-heptanone Cl CH OCH + Cl− 3 3 Because the3 starting material is an ester and the target molecule OCH3 has more carbons than the starting material, a Claisen condensation Claisen condensation forms a methyl acetate acetyl chloride appears to be a good way to start this synthesis. The b-keto ester that can be easily alkylated at the desired carbon because it is flanked by two carbonyl groups. Acid-catalyzed hydrolysis forms