CONTENTS Preface xxv INTRODUCTION he Origins of Organic Chemistry 1 Berzelius, Wohler. and vitalism 1 The Structural Theory 3 Electronic Theories of Structure and Reactivity 3 The Influence of Organic Chemistry 4 Computers and Organic Chemistry 4 Challenges and Opportunities 5 Where Did the Carbon Come from? 6 CHAPTER 1 CHEMICAL BONDING 7 1.1 Atoms. Electrons, and Orbitals 7 1.2 lonic Bonds 11 1.3 Covalent Bonds 1.4 Double Bonds and Triple Bonds 14 1.5 Polar Covalent Bonds and Electronegativity 15 6 Formal cha 1.7 Structural Formulas of Organic Molecules 19 1.8 Constitutional Isomers 22 1 1.10 The Shapes of Learning By Modeling 27 1.11 Molecular Dipole Moments 30 1.12 Electron Waves and Chemical Bonds 31 1.13 Bonding in H2: The Valence Bond Model 32 1.14 Bonding in H2 The Molecular Orbital Model 34 1.15 Bonding in Methane and Orbital Hybridization 35 1.16 spHybridization and Bonding in Ethane 37 1.17 sp2 Hybridization and Bonding in Ethylene 38 1.18 sp Hybridization and Bonding in Acetylene 40 1.19 Which Theory of Chemical Bonding Is Best? 42 1.20 SUMMARY 43 PROBLEMS 47 CHAPTER 2 ALKANES 2.2 Reactive Sites in Hydrocarbons 54 2.3 The Key Functional Groups 55 Methane and the Biosphere 5e Ethane, and Propane 56 2.4 Introduction to Alkanes: Methane 2.5 Isomeric Alkanes: The butanes Forward Main Men TOC Study Guide Toc Student OLCMHHE Website
CONTENTS xi Preface xxv INTRODUCTION 1 The Origins of Organic Chemistry 1 Berzelius, Wöhler, and Vitalism 1 The Structural Theory 3 Electronic Theories of Structure and Reactivity 3 The Influence of Organic Chemistry 4 Computers and Organic Chemistry 4 Challenges and Opportunities 5 Where Did the Carbon Come From? 6 CHAPTER 1 CHEMICAL BONDING 7 1.1 Atoms, Electrons, and Orbitals 7 1.2 Ionic Bonds 11 1.3 Covalent Bonds 12 1.4 Double Bonds and Triple Bonds 14 1.5 Polar Covalent Bonds and Electronegativity 15 1.6 Formal Charge 16 1.7 Structural Formulas of Organic Molecules 19 1.8 Constitutional Isomers 22 1.9 Resonance 23 1.10 The Shapes of Some Simple Molecules 26 Learning By Modeling 27 1.11 Molecular Dipole Moments 30 1.12 Electron Waves and Chemical Bonds 31 1.13 Bonding in H2: The Valence Bond Model 32 1.14 Bonding in H2: The Molecular Orbital Model 34 1.15 Bonding in Methane and Orbital Hybridization 35 1.16 sp3 Hybridization and Bonding in Ethane 37 1.17 sp2 Hybridization and Bonding in Ethylene 38 1.18 sp Hybridization and Bonding in Acetylene 40 1.19 Which Theory of Chemical Bonding Is Best? 42 1.20 SUMMARY 43 PROBLEMS 47 CHAPTER 2 ALKANES 53 2.1 Classes of Hydrocarbons 53 2.2 Reactive Sites in Hydrocarbons 54 2.3 The Key Functional Groups 55 2.4 Introduction to Alkanes: Methane, Ethane, and Propane 56 2.5 Isomeric Alkanes: The Butanes 57 Methane and the Biosphere 58
CONTENTS 2.6 Higher n-Alkanes 59 2.7 The CsH12 Isomers 5 2.8 IUPAC Nomenclature of unbranched alkanes 61 2.9 Applying the IUPAC Rules: The Names of the C6H14 isomers 62 A Brief History of Systematic Organic Nomenclature 63 2.10 Alkyl Groups 65 2.11 IUPAC Names of Highly Branched Alkanes 60 2. 12 Cycloalkane Nomenclature 68 2.13 Sources of alkanes and cycloalkanes 69 2. 14 Physical Properties of Alkanes and Cycloalkanes 71 2.15 Chemical Properties. Combustion of Alkanes 74 Thermochemistry 77 2.16 Oxidation-Reduction in Organic Chemistry 78 2.17 SUMMARY 80 PROBLEMS 83 CHAPTER 3 CONFORMATIONS OF ALKANES AND CYCLOALKANES 3.1 Conformational Analysis of Ethane 90 3. 2 Conformational Analysis of Butane 94 Molecular Mechanics Applied to Alkanes and Cycloalkanes 96 3.3 Conformations of Higher Alkanes 97 3.4 The Shapes of Cycloalkanes: Planar or Nonplanar? 98 3.5 Conformations of cyclohexane 99 3.6 Axial and Equatorial Bonds in Cyclohexane 100 3.7 Conformational Inversion(Ring Flipping)in Cyclohexane 103 3.8 Conformational Analysis of Monosubstituted Cyclohexanes 104 Enthalpy, Free Energy, and Equilibrium Constant 106 3.9 Small Rings: Cyclopropane and Cyclobutane 106 3.10 Cyclopentane 108 3.11 Medium and Large Rings 108 3.12 Disubstituted Cycloalkanes: Stereoisomers 108 3.13 Conformational Analysis of Disubstituted Cyclohexanes 110 3. 14 Polycyclic Ring Systems 114 3.15 Heterocyclic Compounds 116 3.16 SUMMARY 117 PROBLEMS 120 CHAPTER 4 ALCOHOLS AND ALKYL HALIDES 4.1 IUPAC Nomenclature of Alkyl Halides 127 4.2 IUPAC Nomenclature of alcohols 127 4.3 Classes of Alcohols and Alkyl Halides 128 4.4 Bonding in Alcohols and Alkyl Halides 129 4.5 Physical Properties of Alcohols and Alkyl Halides: Intermolecular Forces 130 4.6 Acids and Bases: General Principles 133 4.7 Acid-Base Reactions: A Mechanism for Proton transfer 1 4.8 Preparation of Alkyl Halides from Alcohols and Hydrogen Halides 137 4.9 Mechanism of the Reaction of Alcohols with Hydrogen Halides 139 4.10 Structure, Bonding, and Stability of Carbocations 140 Forward Main Men TOC Study Guide Toc Student OLCMHHE Website
xii CONTENTS 2.6 Higher n-Alkanes 59 2.7 The C5H12 Isomers 59 2.8 IUPAC Nomenclature of Unbranched Alkanes 61 2.9 Applying the IUPAC Rules: The Names of the C6H14 Isomers 62 A Brief History of Systematic Organic Nomenclature 63 2.10 Alkyl Groups 65 2.11 IUPAC Names of Highly Branched Alkanes 66 2.12 Cycloalkane Nomenclature 68 2.13 Sources of Alkanes and Cycloalkanes 69 2.14 Physical Properties of Alkanes and Cycloalkanes 71 2.15 Chemical Properties. Combustion of Alkanes 74 Thermochemistry 77 2.16 Oxidation–Reduction in Organic Chemistry 78 2.17 SUMMARY 80 PROBLEMS 83 CHAPTER 3 CONFORMATIONS OF ALKANES AND CYCLOALKANES 89 3.1 Conformational Analysis of Ethane 90 3.2 Conformational Analysis of Butane 94 Molecular Mechanics Applied to Alkanes and Cycloalkanes 96 3.3 Conformations of Higher Alkanes 97 3.4 The Shapes of Cycloalkanes: Planar or Nonplanar? 98 3.5 Conformations of Cyclohexane 99 3.6 Axial and Equatorial Bonds in Cyclohexane 100 3.7 Conformational Inversion (Ring Flipping) in Cyclohexane 103 3.8 Conformational Analysis of Monosubstituted Cyclohexanes 104 Enthalpy, Free Energy, and Equilibrium Constant 106 3.9 Small Rings: Cyclopropane and Cyclobutane 106 3.10 Cyclopentane 108 3.11 Medium and Large Rings 108 3.12 Disubstituted Cycloalkanes: Stereoisomers 108 3.13 Conformational Analysis of Disubstituted Cyclohexanes 110 3.14 Polycyclic Ring Systems 114 3.15 Heterocyclic Compounds 116 3.16 SUMMARY 117 PROBLEMS 120 CHAPTER 4 ALCOHOLS AND ALKYL HALIDES 126 4.1 IUPAC Nomenclature of Alkyl Halides 127 4.2 IUPAC Nomenclature of Alcohols 127 4.3 Classes of Alcohols and Alkyl Halides 128 4.4 Bonding in Alcohols and Alkyl Halides 129 4.5 Physical Properties of Alcohols and Alkyl Halides: Intermolecular Forces 130 4.6 Acids and Bases: General Principles 133 4.7 Acid–Base Reactions: A Mechanism for Proton Transfer 136 4.8 Preparation of Alkyl Halides from Alcohols and Hydrogen Halides 137 4.9 Mechanism of the Reaction of Alcohols with Hydrogen Halides 139 4.10 Structure, Bonding, and Stability of Carbocations 140
CONTENTS 4.11 Potential Energy Diagrams for Multistep Reactions: The SN1 Mechanism 143 4.12 Effect of alcohol structure on reaction rate 145 4.13 Reaction of Primary Alcohols with Hydrogen Halides: The SN2 4. 14 Other Methods for Converting Alcohols to Alkyl Halides 147 4.15 Halogenation of Alkanes 148 4.16 Chlorination of methane 148 4. 17 Structure and Stability of free Radicals 149 4.18 Mechanism of Methane Chlorination 153 From Bond Energies to Heats of Reaction 155 4.19 Halogenation of Higher Alkanes 156 4.20 SUMMARY 159 PROBLEMS 163 CHAPTER 5 STRUCTURE AND PREPARATION OF ALKENES: ELIMINATION REACTIONS 5.1 Alkene Nomenclature 167 Ethylene 168 5.2 Structure and Bonding in Alkenes 170 5.3 Isomerism in alkenes 172 5.4 Naming Stereoisomeric Alkenes by the E-Z Notational System 173 5.6 Relative Stabilities of alkenes 176 5.7 Cycloalkenes 180 5.8 Preparation of Alkenes: Elimination Reactions 181 5.9 Dehydration of Alcohols 182 5.10 Regioselectivity in Alcohol Dehydration: The Zaitsev Rule 183 5.11 Stereoselectivity in Alcohol Dehydration 184 5.12 The Mechanism of Acid-Catalyzed Dehydration of Alcohols 185 5.13 Rearrangements in Alcohol Dehydration 187 5.14 Dehydrohalogenation of Alkyl Halides 190 5.15 Mechanism of the Dehydrohalogenation of Alkyl Halides: The E2 Mechanism 192 5.16 Anti Elimination in E2 Reactions: Stereoelectronic Effects 194 5.17 A Different Mechanism for Alkyl Halide Elimination: The E1 5.18 SUMMARY 198 PROBLEMS 202 CHAPTER 6 REACTIONS OF ALKENES: ADDITION REACTIONS ntion of alk 6.2 Heats of Hydrogenation 209 6.3 Stereochemistry of Alkene Hydrogenation 212 6.4 Electrophilic Addition of Hydrogen Halides to Alkenes 213 6.5 Regioselectivity of Hydrogen Halide Addition: Markovnikov's Rule 214 6.6 Mechanistic Basis for markovnikov' s rule 2 Rules. Laws. Theories, and the scientific Method 217 6.7 Carbocation Rearrangements in Hydrogen Halide Addition to Alkenes 219 6.8 Free-Radical Addition of Hydrogen Bromide to Alkenes 220 Forward Main Men TOC Study Guide Toc Student OLCMHHE Website
CONTENTS xiii 4.11 Potential Energy Diagrams for Multistep Reactions: The SN1 Mechanism 143 4.12 Effect of Alcohol Structure on Reaction Rate 145 4.13 Reaction of Primary Alcohols with Hydrogen Halides: The SN2 Mechanism 146 4.14 Other Methods for Converting Alcohols to Alkyl Halides 147 4.15 Halogenation of Alkanes 148 4.16 Chlorination of Methane 148 4.17 Structure and Stability of Free Radicals 149 4.18 Mechanism of Methane Chlorination 153 From Bond Energies to Heats of Reaction 155 4.19 Halogenation of Higher Alkanes 156 4.20 SUMMARY 159 PROBLEMS 163 CHAPTER 5 STRUCTURE AND PREPARATION OF ALKENES: ELIMINATION REACTIONS 167 5.1 Alkene Nomenclature 167 Ethylene 168 5.2 Structure and Bonding in Alkenes 170 5.3 Isomerism in Alkenes 172 5.4 Naming Stereoisomeric Alkenes by the E–Z Notational System 173 5.5 Physical Properties of Alkenes 174 5.6 Relative Stabilities of Alkenes 176 5.7 Cycloalkenes 180 5.8 Preparation of Alkenes: Elimination Reactions 181 5.9 Dehydration of Alcohols 182 5.10 Regioselectivity in Alcohol Dehydration: The Zaitsev Rule 183 5.11 Stereoselectivity in Alcohol Dehydration 184 5.12 The Mechanism of Acid-Catalyzed Dehydration of Alcohols 185 5.13 Rearrangements in Alcohol Dehydration 187 5.14 Dehydrohalogenation of Alkyl Halides 190 5.15 Mechanism of the Dehydrohalogenation of Alkyl Halides: The E2 Mechanism 192 5.16 Anti Elimination in E2 Reactions: Stereoelectronic Effects 194 5.17 A Different Mechanism for Alkyl Halide Elimination: The E1 Mechanism 196 5.18 SUMMARY 198 PROBLEMS 202 CHAPTER 6 REACTIONS OF ALKENES: ADDITION REACTIONS 208 6.1 Hydrogenation of Alkenes 208 6.2 Heats of Hydrogenation 209 6.3 Stereochemistry of Alkene Hydrogenation 212 6.4 Electrophilic Addition of Hydrogen Halides to Alkenes 213 6.5 Regioselectivity of Hydrogen Halide Addition: Markovnikov’s Rule 214 6.6 Mechanistic Basis for Markovnikov’s Rule 216 Rules, Laws, Theories, and the Scientific Method 217 6.7 Carbocation Rearrangements in Hydrogen Halide Addition to Alkenes 219 6.8 Free-Radical Addition of Hydrogen Bromide to Alkenes 220
CONTENTS 6.9 Addition of sulfuric Acid to Alkenes 223 6.10 Acid-Catalyzed Hydration of Alkenes 225 6.11 Hydroboration-Oxidation of Alkenes 227 6. 12 Stereochemistry of Hydroboration-Oxidation 22 6.13 Mechanism of Hydroboration-Oxidation 230 6. 14 Addition of Halogens to Alkenes 233 6.15 Stereochemistry of Halogen Addition 233 6.16 Mechanism of Halogen Addition to Alkenes: Halonium lons 234 6. 17 Conversion of Alkenes to Vicinal Halohydrins 236 6. 18 Epoxidation of Alkenes 238 6. 19 Ozonolysis of Alkenes 240 6. 20 Introduction to Organic Chemical Synthesis 243 6.21 Reactions of Alkenes with Alkenes: Polymerization 244 Ethylene and Propene: The Most Important Industrial Organic Chemicals 248 6.22 SUMMARY 249 PROBLEMS 252 CHAPTER 7 STEREOCHEMISTRY 259 7.1 Molecular Chirality: Enantiomers 259 7. 2 The Stereogenic Center 260 7.3 Symmetry in Achiral Structures 264 7. 4 Properties of Chiral Molecules: Optical Activity 265 7.5 Absolute and Relative Configuration 26 7.6 The Cahn-Ingold-Prelog R-S Notational System 268 7.7 Fischer Projections 271 7.8 Physical Properties of Enantiomers 272 Chiral Drugs 273 7.9 Reactions That Create a Stereogenic Center 274 7.10 Chiral Molecules with Two Stereogenic Centers 276 7. 11 Achiral Molecules with Two Stereogenic Centers 279 Chirality of Disubstituted Cyclohexanes 281 7.12 Molecules with Multiple Stereogenic Centers 282 7.13 Reactions That Produce Diastereomers 284 7.14 Resolution of enantiomers 286 7.15 Stereoregular Polymers 288 7.16 Stereogenic Centers Other Than Carbon 290 7.17 SUMMARY 290 PROBLEMS 293 CHAPTER 8 NUCLEOPHILIC SUBSTITUTION 8.1 Functional Group Transformation by Nucleophilic Substitution 302 8. 2 Relative Reactivity of Halide Leaving Groups 305 8.3 The SN2 Mechanism of Nucleophilic Substitution 306 8.4 Stereochemistry of SN2 Reactions 307 8.5 How SN2 Reactions Occur 308 8.6 Steric Effects in SN2 Reactions 310 8.7 Nucleophiles and Nucleophilicity 312 An Enzyme-Catalyzed Nucleophilic Substitution of an Alkyl Halide 314 Forward Main Men TOC Study Guide Toc Student OLCMHHE Website
xiv CONTENTS 6.9 Addition of Sulfuric Acid to Alkenes 223 6.10 Acid-Catalyzed Hydration of Alkenes 225 6.11 Hydroboration–Oxidation of Alkenes 227 6.12 Stereochemistry of Hydroboration–Oxidation 229 6.13 Mechanism of Hydroboration–Oxidation 230 6.14 Addition of Halogens to Alkenes 233 6.15 Stereochemistry of Halogen Addition 233 6.16 Mechanism of Halogen Addition to Alkenes: Halonium Ions 234 6.17 Conversion of Alkenes to Vicinal Halohydrins 236 6.18 Epoxidation of Alkenes 238 6.19 Ozonolysis of Alkenes 240 6.20 Introduction to Organic Chemical Synthesis 243 6.21 Reactions of Alkenes with Alkenes: Polymerization 244 Ethylene and Propene: The Most Important Industrial Organic Chemicals 248 6.22 SUMMARY 249 PROBLEMS 252 CHAPTER 7 STEREOCHEMISTRY 259 7.1 Molecular Chirality: Enantiomers 259 7.2 The Stereogenic Center 260 7.3 Symmetry in Achiral Structures 264 7.4 Properties of Chiral Molecules: Optical Activity 265 7.5 Absolute and Relative Configuration 267 7.6 The Cahn–Ingold–Prelog R–S Notational System 268 7.7 Fischer Projections 271 7.8 Physical Properties of Enantiomers 272 Chiral Drugs 273 7.9 Reactions That Create a Stereogenic Center 274 7.10 Chiral Molecules with Two Stereogenic Centers 276 7.11 Achiral Molecules with Two Stereogenic Centers 279 Chirality of Disubstituted Cyclohexanes 281 7.12 Molecules with Multiple Stereogenic Centers 282 7.13 Reactions That Produce Diastereomers 284 7.14 Resolution of Enantiomers 286 7.15 Stereoregular Polymers 288 7.16 Stereogenic Centers Other Than Carbon 290 7.17 SUMMARY 290 PROBLEMS 293 CHAPTER 8 NUCLEOPHILIC SUBSTITUTION 302 8.1 Functional Group Transformation by Nucleophilic Substitution 302 8.2 Relative Reactivity of Halide Leaving Groups 305 8.3 The SN2 Mechanism of Nucleophilic Substitution 306 8.4 Stereochemistry of SN2 Reactions 307 8.5 How SN2 Reactions Occur 308 8.6 Steric Effects in SN2 Reactions 310 8.7 Nucleophiles and Nucleophilicity 312 An Enzyme-Catalyzed Nucleophilic Substitution of an Alkyl Halide 314
CONTENTS 8.8 The SN1 Mechanism of Nucleophilic Substitution 315 8.9 Carbocation Stability and Sn1 Reaction Rates 315 8.10 Stereochemistry of Sn1 Re 318 8.11 Carbocation Rearrangements in SN1 Reactions 319 8.12 Effect of Solvent on the Rate of Nucleophilic Substitution 320 8.13 Substitution and Elimination as Competing Reactions 323 8.14 Sulfonate Esters as Substrates in Nucleophilic Substitution 326 8.15 Looking Back: Reactions of Alcohols with Hydrogen Halides 329 8.16 SUMMARY 330 PROBLEMS 332 CHAPTER 9 ALKYNES 339 9.1 Sources of Alkynes 339 9.2 Nomenclature 340 9.3 Physical Properties of Alkynes 341 9.4 Structure and Bonding in Alkynes: sp Hybridization 341 Natural and"Designed"Enediyne Antibiotics 344 9.5 Acidity of acetylene and Terminal alkynes 344 9.6 Preparation of Alkynes by Alkylation of Acetylene and Terminal Alkynes 9.7 Preparation of Alkynes by Elimination Reactions 348 9.8 Reactions of Alkynes 350 9.9 Hydr 9.10 Metal-Ammonia Reduction of Alkynes 351 9.11 Addition of Hydrogen Halides to Alkynes 352 9.12 Hydration of Alkynes 355 9.13 Addition of Halogens to Alkynes 356 9.14 Ozonolysis of Alkynes 357 9.15 SUMMARY 357 PROBLEMS 358 CHAPTER 10 CONJUGATION IN ALKADIENES AND ALLYLIC SYSTEMS 365 10.1 The Allyl Group 365 Allylic Carbocations 10.3 Allylic Free Radicals 10.4 Allylic Halogenation 370 10.5 Classes of dienes 372 10.6 Relative Stabilities of dienes 374 10.7 Bonding in Conjugated Dienes 375 10.8 Bonding in Allenes 377 10.9 Preparation of Dienes 378 10.10 Addition of Hydrogen Halides to Conjugated Dienes 379 10.11 Halogen Addition to Dienes 382 10.12 The Diels-Alder reaction 382 Diene Polymers 383 10.13 The T Molecular Orbitals of Ethylene and 1, 3-Butadiene 386 10.14 A T Molecular Orbital Analysis of the Diels-Alder Reaction 388 10.15 SUMMAR PROBLEMS 3 Forward Main Men TOC Study Guide Toc Student OLCMHHE Website
CONTENTS xv 8.8 The SN1 Mechanism of Nucleophilic Substitution 315 8.9 Carbocation Stability and SN1 Reaction Rates 315 8.10 Stereochemistry of SN1 Reactions 318 8.11 Carbocation Rearrangements in SN1 Reactions 319 8.12 Effect of Solvent on the Rate of Nucleophilic Substitution 320 8.13 Substitution and Elimination as Competing Reactions 323 8.14 Sulfonate Esters as Substrates in Nucleophilic Substitution 326 8.15 Looking Back: Reactions of Alcohols with Hydrogen Halides 329 8.16 SUMMARY 330 PROBLEMS 332 CHAPTER 9 ALKYNES 339 9.1 Sources of Alkynes 339 9.2 Nomenclature 340 9.3 Physical Properties of Alkynes 341 9.4 Structure and Bonding in Alkynes: sp Hybridization 341 Natural and “Designed” Enediyne Antibiotics 344 9.5 Acidity of Acetylene and Terminal Alkynes 344 9.6 Preparation of Alkynes by Alkylation of Acetylene and Terminal Alkynes 346 9.7 Preparation of Alkynes by Elimination Reactions 348 9.8 Reactions of Alkynes 350 9.9 Hydrogenation of Alkynes 350 9.10 Metal–Ammonia Reduction of Alkynes 351 9.11 Addition of Hydrogen Halides to Alkynes 352 9.12 Hydration of Alkynes 355 9.13 Addition of Halogens to Alkynes 356 9.14 Ozonolysis of Alkynes 357 9.15 SUMMARY 357 PROBLEMS 358 CHAPTER 10 CONJUGATION IN ALKADIENES AND ALLYLIC SYSTEMS 365 10.1 The Allyl Group 365 10.2 Allylic Carbocations 366 10.3 Allylic Free Radicals 370 10.4 Allylic Halogenation 370 10.5 Classes of Dienes 372 10.6 Relative Stabilities of Dienes 374 10.7 Bonding in Conjugated Dienes 375 10.8 Bonding in Allenes 377 10.9 Preparation of Dienes 378 10.10 Addition of Hydrogen Halides to Conjugated Dienes 379 10.11 Halogen Addition to Dienes 382 10.12 The Diels–Alder Reaction 382 Diene Polymers 383 10.13 The π Molecular Orbitals of Ethylene and 1,3-Butadiene 386 10.14 A π Molecular Orbital Analysis of the Diels–Alder Reaction 388 10.15 SUMMARY 390 PROBLEMS 393
CONTENTS CHAPTER 11 ARENES AND AROMATICITY 11.1 Benzene 399 11.2 Kekule and the structure of benzene 399 Benzene, Dreams, and Creative Thinking 401 11.3 A Resonance Picture of Bonding in Benzene 402 11. 4 The Stability of Benzene 403 11.5 An Orbital Hybridization View of Bonding in Benzene 405 11.6 The I Molecular Orbitals of benzene 405 11.7 Substituted derivatives of benzene and their nomenclature 406 11.8 Polycyclic Aromatic Hydrocarbons 408 Carbon Clusters, Fullerenes, and Nanotubes 410 11.9 Physical Properties of Arenes 411 11.10 Reactions of Arenes: A Preview 411 11.11 The Birch Reduction 412 11.12 Free-Radical Halogenation of Alkylbenzenes 414 11.13 Oxidation of Alkylbenzenes 416 11.14 Nucleophilic Substitution in Benzylic Halides 417 11.15 Preparation of Alkenylbenzenes 419 11.16 Addition Reactions of Alkenylbenzenes 419 11.17 Polymerization of Styrene 42 11.18 Cyclobutadiene and Cyclooctatetraene 422 11.19 Huckel's Rule: Annulenes 423 11.20 Aromatic lons 426 11.21 Heterocyclic Aromatic Compounds 430 11.22 Heterocyclic Aromatic Compounds and Huckel's Rule 432 11.23 SUMMARY 433 PROBLEMS 437 CHAPTEER 12 REACTIONS OF ARENES: ELECTROPHILIC AROMATIC SUBSTITUTION 443 2.1 Representative Electrophilic Aromatic Substitution Reactions of 12.2 Mechanistic Principles of Electrophilic Aromatic Substitution 444 12.3 Nitration of benzene 447 12.4 Sulfonation of benzene 448 12.5 Halogenation of Benzene 448 12.6 Friedel-Crafts Alkylation of Benzene 12.7 Friedel-Crafts Acylation of Benzene 12.8 Synthesis of Alkylbenzenes by Acylation-Reduction 455 12.9 Rate and Regioselectivity in Electrophilic Aromatic Substitution 457 12.10 Rate and Regioselectivity in the Nitration of Toluene 458 12.11 Rate and Regioselectivity in the Nitration of (trifluoromethylbenzene 461 12.12 Substituent Effects in Electrophilic Aromatic Substitution: Activating 12.13 Substituent Effects in Electrophilic Aromatic Substitution: Strongly Deactivating Substituents 466 12.14 Substituent Effects in Electrophilic Aromatic Substitution: Halogens 469 12.15 Multiple Substituent Effects 470 12.16 Regioselective Synthesis of Disubstituted Aromatic Compounds 472 Forward Main Men TOC Study Guide Toc Student OLCMHHE Website
xvi CONTENTS CHAPTER 11 ARENES AND AROMATICITY 398 11.1 Benzene 399 11.2 Kekulé and the Structure of Benzene 399 Benzene, Dreams, and Creative Thinking 401 11.3 A Resonance Picture of Bonding in Benzene 402 11.4 The Stability of Benzene 403 11.5 An Orbital Hybridization View of Bonding in Benzene 405 11.6 The π Molecular Orbitals of Benzene 405 11.7 Substituted Derivatives of Benzene and Their Nomenclature 406 11.8 Polycyclic Aromatic Hydrocarbons 408 Carbon Clusters, Fullerenes, and Nanotubes 410 11.9 Physical Properties of Arenes 411 11.10 Reactions of Arenes: A Preview 411 11.11 The Birch Reduction 412 11.12 Free-Radical Halogenation of Alkylbenzenes 414 11.13 Oxidation of Alkylbenzenes 416 11.14 Nucleophilic Substitution in Benzylic Halides 417 11.15 Preparation of Alkenylbenzenes 419 11.16 Addition Reactions of Alkenylbenzenes 419 11.17 Polymerization of Styrene 421 11.18 Cyclobutadiene and Cyclooctatetraene 422 11.19 Hückel’s Rule: Annulenes 423 11.20 Aromatic Ions 426 11.21 Heterocyclic Aromatic Compounds 430 11.22 Heterocyclic Aromatic Compounds and Hückel’s Rule 432 11.23 SUMMARY 433 PROBLEMS 437 CHAPTER 12 REACTIONS OF ARENES: ELECTROPHILIC AROMATIC SUBSTITUTION 443 12.1 Representative Electrophilic Aromatic Substitution Reactions of Benzene 444 12.2 Mechanistic Principles of Electrophilic Aromatic Substitution 444 12.3 Nitration of Benzene 447 12.4 Sulfonation of Benzene 448 12.5 Halogenation of Benzene 448 12.6 Friedel–Crafts Alkylation of Benzene 450 12.7 Friedel–Crafts Acylation of Benzene 453 12.8 Synthesis of Alkylbenzenes by Acylation–Reduction 455 12.9 Rate and Regioselectivity in Electrophilic Aromatic Substitution 457 12.10 Rate and Regioselectivity in the Nitration of Toluene 458 12.11 Rate and Regioselectivity in the Nitration of (Trifluoromethyl)benzene 461 12.12 Substituent Effects in Electrophilic Aromatic Substitution: Activating Substituents 463 12.13 Substituent Effects in Electrophilic Aromatic Substitution: Strongly Deactivating Substituents 466 12.14 Substituent Effects in Electrophilic Aromatic Substitution: Halogens 469 12.15 Multiple Substituent Effects 470 12.16 Regioselective Synthesis of Disubstituted Aromatic Compounds 472
CONTENTS 12.17 Substitution in Naphthalene 474 12.18 Substitution in Heterocyclic Aromatic Compounds 475 12.19 SUMMARY 477 PROBLEMS 480 CHAPTER 13 SPECTROSCOPY 13.1 Principles of Molecular Spectroscopy: Electromagnetic Radiation 488 13.2 Principles of Molecular Spectroscopy: Quantized Energy States 489 13.3 Introduction to H NMR Spectroscopy 490 13.4 Nuclear Shielding and h chemical Shifts 493 13.6 Interpreting Proton NMR Spectra 497 cal 13.5 Effects of molecular structure on h chemical shifts 494 13.7 Spin-Spin Splitting in NMR Spectroscopy 500 13.8 Splitting Patterns: The Ethyl Group 503 13.9 Splitting Patterns: The Isopropyl Group 505 13.10 Splitting Patterns: Pairs of Doublets 505 13.11 Complex Splitting Patterns 507 13.12 H NMR Spectra of Alcohols 509 13.13 NMR and Conformations 510 13.14C NMR Spectroscopy 510 13.15 C Chemical shifts 512 13.16 13C NMR and Peak Intensities 513 13.17C-H Coupling 515 13.18 Using dEPT to Count the Hydrogens Attached to 13C515 Magnetic Resonance Imaging 517 13.19 Infrared Spectroscopy 13.20 Ultraviolet-Visible (UV-VIS)Spectroscopy 522 Gas Chromatography, GC/MS, and MS/Ms 530 13.22 Molecular formula as a clue to structure 532 13.23 SUMMARY 533 PROBLEMS 536 CHAPTER 14 ORGANOMETALLIC COMPOUNDS 546 14.1 Organometallic Nomenclature 547 14.2 Carbon-Metal Bonds in Organometallic Compounds 547 14.3 Preparation of Organolithium Compounds 549 14.4 Preparation of Organomagnesium Compounds: Grignard Reagents 550 14.5 Organolithium and Organomagnesium Compounds as Bronsted Bases 551 14.6 Synthesis of Alcohols Using Grignard Reagents 553 14.7 Synthesis of Alcohols Using Organolithium Reagents 554 14.8 Synthesis of Acetylenic Alcohols 556 9 Retrosynthetic Analysis 557 14.10 Preparation of Tertiary Alcohols from Esters and Grignard Reagents 560 14.11 Alkane Synthesis Using Organocopper Reagents 561 14.12 An Organozinc Reagent for Cyclopropane Synthesis 563 14.13 Carbenes and Carbenoids 565 14 14 Transition-Metal Organometallic Compounds 566 14.15 Ziegler-Natta Catalysis of Alkene Polymerization 567 Forward Main Men TOC Study Guide Toc Student OLCMHHE Website
CONTENTS xvii 12.17 Substitution in Naphthalene 474 12.18 Substitution in Heterocyclic Aromatic Compounds 475 12.19 SUMMARY 477 PROBLEMS 480 CHAPTER 13 SPECTROSCOPY 487 13.1 Principles of Molecular Spectroscopy: Electromagnetic Radiation 488 13.2 Principles of Molecular Spectroscopy: Quantized Energy States 489 13.3 Introduction to 1 H NMR Spectroscopy 490 13.4 Nuclear Shielding and 1 H Chemical Shifts 493 13.5 Effects of Molecular Structure on 1 H Chemical Shifts 494 13.6 Interpreting Proton NMR Spectra 497 13.7 Spin–Spin Splitting in NMR Spectroscopy 500 13.8 Splitting Patterns: The Ethyl Group 503 13.9 Splitting Patterns: The Isopropyl Group 505 13.10 Splitting Patterns: Pairs of Doublets 505 13.11 Complex Splitting Patterns 507 13.12 1 H NMR Spectra of Alcohols 509 13.13 NMR and Conformations 510 13.14 13C NMR Spectroscopy 510 13.15 13C Chemical Shifts 512 13.16 13C NMR and Peak Intensities 513 13.17 13C—1 H Coupling 515 13.18 Using DEPT to Count the Hydrogens Attached to 13C 515 Magnetic Resonance Imaging 517 13.19 Infrared Spectroscopy 518 13.20 Ultraviolet-Visible (UV-VIS) Spectroscopy 522 13.21 Mass Spectrometry 526 Gas Chromatography, GC/MS, and MS/MS 530 13.22 Molecular Formula as a Clue to Structure 532 13.23 SUMMARY 533 PROBLEMS 536 CHAPTER 14 ORGANOMETALLIC COMPOUNDS 546 14.1 Organometallic Nomenclature 547 14.2 Carbon–Metal Bonds in Organometallic Compounds 547 14.3 Preparation of Organolithium Compounds 549 14.4 Preparation of Organomagnesium Compounds: Grignard Reagents 550 14.5 Organolithium and Organomagnesium Compounds as Brønsted Bases 551 14.6 Synthesis of Alcohols Using Grignard Reagents 553 14.7 Synthesis of Alcohols Using Organolithium Reagents 554 14.8 Synthesis of Acetylenic Alcohols 556 14.9 Retrosynthetic Analysis 557 14.10 Preparation of Tertiary Alcohols from Esters and Grignard Reagents 560 14.11 Alkane Synthesis Using Organocopper Reagents 561 14.12 An Organozinc Reagent for Cyclopropane Synthesis 563 14.13 Carbenes and Carbenoids 565 14.14 Transition-Metal Organometallic Compounds 566 14.15 Ziegler–Natta Catalysis of Alkene Polymerization 567
CONTENTS An Organometallic Compound That Occurs Naturall Enzyme B12 568 PROBLEMS 573 CHAPTER 15 ALCOHOLS, DIOLS, AND THIOLS 579 15.1 Sources of alcohols 579 15.2 Preparation of Alcohols by Reduction of Aldehydes and Ketones 583 15.3 Preparation of Alcohols by Reduction of Carboxylic Acids and Esters 587 15.4 Preparation of Alcohols from Epoxides 587 15.5 Preparation of Diols 589 15.6 Reactions of Alcohols: a Review and a preview 15.7 Conversion of alcohols to ethers 590 15.8 Esterification 593 15.9 Esters of Inorganic Acids 595 15.10 Oxidation of Alcohols 596 Economic and Environmental Factors in Organic Synthesis 598 15.11 Biological Oxidation of Alcohols 600 15.12 Oxidative Cleavage of Vicinal Diols 602 15.14 Properties of Thiols 604 15.15 Spectroscopic Analysis of Alcoho 15.16 SUMMARY PROBLEMS CHAPTER 16 ETHERS EPOXIDES, AND SULFIDES 619 16.1 Nomenclature of Ethers, Epoxides, and Sulfides 619 16.2 Structure and Bonding in Ethers and Epoxides 621 Properties of Ethers 62 16.4 Crown Ethers 622 Polyether Antibiotics 624 16.5 Preparation of Ethers 625 16.6 The Williamson Ether Synthesis 626 16.7 Reactions of ethers: a review and a preview 627 16.8 Acid-Catalyzed Cleavage of Ethers 628 16.9 Preparation of Epoxides: A Review and a Preview 630 16.10 Conversion of Vicinal Halohydrins to Epoxides 630 16.11 Reactions of Epoxides: A Review and a Preview 632 16.12 Nucleophilic Ring-Opening reactions of Epoxides 633 16.13 Acid-Catalyzed Ring-Opening Reactions of Epoxides 635 16 14 Epoxides in Biological Processes 637 16. 15 Preparation of Sulfides 638 16.16 Oxidation of Sulfides: Sulfoxides and Sulfones 639 16.17 Alkylation of Sulfides: Sulfonium Salts 640 16.18 Spectroscopic Analysis of Ethers 64 16.19 SUMMARY 643 PROBLEMS 647 Forward Main Men TOC Study Guide Toc Student OLCMHHE Website
xviii CONTENTS An Organometallic Compound That Occurs Naturally: Coenzyme B12 568 14.16 SUMMARY 570 PROBLEMS 573 CHAPTER 15 ALCOHOLS, DIOLS, AND THIOLS 579 15.1 Sources of Alcohols 579 15.2 Preparation of Alcohols by Reduction of Aldehydes and Ketones 583 15.3 Preparation of Alcohols by Reduction of Carboxylic Acids and Esters 587 15.4 Preparation of Alcohols from Epoxides 587 15.5 Preparation of Diols 589 15.6 Reactions of Alcohols: A Review and a Preview 590 15.7 Conversion of Alcohols to Ethers 590 15.8 Esterification 593 15.9 Esters of Inorganic Acids 595 15.10 Oxidation of Alcohols 596 Economic and Environmental Factors in Organic Synthesis 598 15.11 Biological Oxidation of Alcohols 600 15.12 Oxidative Cleavage of Vicinal Diols 602 15.13 Preparation of Thiols 603 15.14 Properties of Thiols 604 15.15 Spectroscopic Analysis of Alcohols 605 15.16 SUMMARY 607 PROBLEMS 611 CHAPTER 16 ETHERS, EPOXIDES, AND SULFIDES 619 16.1 Nomenclature of Ethers, Epoxides, and Sulfides 619 16.2 Structure and Bonding in Ethers and Epoxides 621 16.3 Physical Properties of Ethers 622 16.4 Crown Ethers 622 Polyether Antibiotics 624 16.5 Preparation of Ethers 625 16.6 The Williamson Ether Synthesis 626 16.7 Reactions of Ethers: A Review and a Preview 627 16.8 Acid-Catalyzed Cleavage of Ethers 628 16.9 Preparation of Epoxides: A Review and a Preview 630 16.10 Conversion of Vicinal Halohydrins to Epoxides 630 16.11 Reactions of Epoxides: A Review and a Preview 632 16.12 Nucleophilic Ring-Opening Reactions of Epoxides 633 16.13 Acid-Catalyzed Ring-Opening Reactions of Epoxides 635 16.14 Epoxides in Biological Processes 637 16.15 Preparation of Sulfides 638 16.16 Oxidation of Sulfides: Sulfoxides and Sulfones 639 16.17 Alkylation of Sulfides: Sulfonium Salts 640 16.18 Spectroscopic Analysis of Ethers 641 16.19 SUMMARY 643 PROBLEMS 647
CONTENTS CHAPTER 17 ALDEHYDES AND KETONES: NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP 654 17.1 Nomenclature 654 17. 2 Structure and Bonding: The Carbonyl Group 657 17.3 Physical Properties 658 17. 4 Sources of Aldehydes and Ketones 659 17.5 Reactions of Aldehydes and Ketones: A Review and a Preview 661 17.6 Principles of Nucleophilic Addition: Hydration of Aldehydes and 17.7 Cyanohydrin Formation 667 17.8 Acetal Formation 668 17.9 Acetals as Protecting Groups 671 17.10 Reaction with Primary Amines: Imines 672 17.11 Reaction with Secondary Amines: Enamines 674 Imines in Biological Chemistry 675 17.12 The Wittig Reaction 677 17.13 Planning an Alkene Synthesis via the Wittig Reaction 678 17. 14 Stereoselective Addition to Carbonyl Groups 681 17.15 Oxidation of Aldehydes 682 17.16 Baeyer-Villiger Oxidation of Ketones 683 17.17 Spectroscopic Analysis of Aldehydes and Ketones 684 17.18 SUMMARY 688 PROBLEMS 691 CHAPTER 18 ENOLS AND ENOLATES 701 18.1 The a-Carbon Atom and Its Hydrogens 702 18. 2 a Halogenation of Aldehydes and Ketones 703 18.3 Mechanism of a halogenation of aldehydes and Ketones 703 18.4 Enolization and enol content 705 18.5 Stabilized Enols 707 18.6 Base-Catalyzed Enolization: Enolate Anions 708 18.7 The Haloform Reaction 711 The Haloform Reaction and the Biosynthesis of Trihalomethanes 18.8 Some Chemical and Stereochemical Consequences of Enolization 18.9 The Aldol Condensation 715 18.10 Mixed Aldol Condensations 719 18.12 Conjugate Addition to a, B-Unsaturated Carbonyl Compounds 2 720 18.11 Effects of Conjugation in a, B-Unsaturated Aldehydes and Ketones 8.13 Additions of Carbanions to a, B-Unsaturated Ketones: The michael Reaction 724 8.14 Conjugate Addition of Organocopper Reagents to ax, B-Unsaturated Carbonyl Compounds 18.15 Alkylation of Enolate Anions 725 18.16 SUMMARY 726 PROBLEMS 726 Forward Main Men TOC Study Guide Toc Student OLCMHHE Website
CONTENTS xix CHAPTER 17 ALDEHYDES AND KETONES: NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP 654 17.1 Nomenclature 654 17.2 Structure and Bonding: The Carbonyl Group 657 17.3 Physical Properties 658 17.4 Sources of Aldehydes and Ketones 659 17.5 Reactions of Aldehydes and Ketones: A Review and a Preview 661 17.6 Principles of Nucleophilic Addition: Hydration of Aldehydes and Ketones 663 17.7 Cyanohydrin Formation 667 17.8 Acetal Formation 668 17.9 Acetals as Protecting Groups 671 17.10 Reaction with Primary Amines: Imines 672 17.11 Reaction with Secondary Amines: Enamines 674 Imines in Biological Chemistry 675 17.12 The Wittig Reaction 677 17.13 Planning an Alkene Synthesis via the Wittig Reaction 678 17.14 Stereoselective Addition to Carbonyl Groups 681 17.15 Oxidation of Aldehydes 682 17.16 Baeyer–Villiger Oxidation of Ketones 683 17.17 Spectroscopic Analysis of Aldehydes and Ketones 684 17.18 SUMMARY 688 PROBLEMS 691 CHAPTER 18 ENOLS AND ENOLATES 701 18.1 The -Carbon Atom and Its Hydrogens 702 18.2 Halogenation of Aldehydes and Ketones 703 18.3 Mechanism of Halogenation of Aldehydes and Ketones 703 18.4 Enolization and Enol Content 705 18.5 Stabilized Enols 707 18.6 Base-Catalyzed Enolization: Enolate Anions 708 18.7 The Haloform Reaction 711 The Haloform Reaction and the Biosynthesis of Trihalomethanes 713 18.8 Some Chemical and Stereochemical Consequences of Enolization 713 18.9 The Aldol Condensation 715 18.10 Mixed Aldol Condensations 719 18.11 Effects of Conjugation in ,-Unsaturated Aldehydes and Ketones 720 18.12 Conjugate Addition to ,-Unsaturated Carbonyl Compounds 722 18.13 Additions of Carbanions to ,-Unsaturated Ketones: The Michael Reaction 724 18.14 Conjugate Addition of Organocopper Reagents to ,-Unsaturated Carbonyl Compounds 724 18.15 Alkylation of Enolate Anions 725 18.16 SUMMARY 726 PROBLEMS 726
CONTENTS CHAPTER 19 CARBOXYLIC ACIDS 736 19.1 Carboxylic Acid Nomenclature 737 19.2 Structure and Bonding 738 19.3 Physical Properties 739 19.5 Salts of Carboxylic Acids 742 Quantitative Relationships Involving Carboxylic Acids 743 19.6 Substituents and Acid Strength 745 19.7 lonization of substituted Benzoic Acids 747 19.8 Dicarboxylic Acids 748 19.9 Carbonic Acid 749 19.10 Sources of Carboxylic Acids 750 19.11 Synthesis of Carboxylic Acids by the Carboxylation of grignard Reagents 750 19.12 Synthesis of Carboxylic Acids by the Preparation and Hydrolysis of Nitriles 752 9.13 Reactions of Carboxylic Acids: A Review and a Preview 753 19.14 Mechanism of Acid-Catalyzed Esterification 754 19.15 Intramolecular Ester Formation Lactones 758 19.16 a Halogenation of Carboxylic Acids: The Hell-Volhard-Zelinsky Reaction 759 9.17 Decarboxylation of Malonic Acid and Related Compounds 760 19.18 Spectroscopic Analysis of Carboxylic Acids 763 9.19 SUMMARY 765 PROBLEMS 768 CHAPTER 20 CARBOXYLIC ACID DERIVATIVES: NUCLEOPHILIC ACYL SUBSTITUTION 774 20.1 Nomenclature of Carboxylic Acid Derivatives 775 20.2 Structure of Carboxylic Acid Derivatives 777 20.3 Nucleophilic Substitution in Acyl Chlorides 780 20.4 Preparation of Carboxylic Acid Anhydrides 783 20.5 Reactions of Carboxylic Acid Anhydrides 784 20.6 Sources of esters 787 20.7 Physical Properties of Esters 788 20.8 Reactions of esters: a review and a preview 790 20.9 Acid-Catalyzed Ester Hydrolysis 791 20.10 Ester Hydrolysis in Base: Saponification 794 20.11 Reaction of esters with Ammonia and Amines 799 20.12 Thioesters 800 20.13 Preparation of Amides 800 20. 14 Lactams 803 20.15 Imide 20.16 Hydrolysis of Amides 804 20.17 The Hofmann Rearrangement 807 Condensation Polymers: Polyamides and Polyesters 809 20.18 Preparation of Nitriles 813 20.19 Hydrolysis of Nitriles 815 20.20 Addition of Grignard Reagents to Nitriles 816 Forward Main Men TOC Study Guide Toc Student OLCMHHE Website
xx CONTENTS CHAPTER 19 CARBOXYLIC ACIDS 736 19.1 Carboxylic Acid Nomenclature 737 19.2 Structure and Bonding 738 19.3 Physical Properties 739 19.4 Acidity of Carboxylic Acids 740 19.5 Salts of Carboxylic Acids 742 Quantitative Relationships Involving Carboxylic Acids 743 19.6 Substituents and Acid Strength 745 19.7 Ionization of Substituted Benzoic Acids 747 19.8 Dicarboxylic Acids 748 19.9 Carbonic Acid 749 19.10 Sources of Carboxylic Acids 750 19.11 Synthesis of Carboxylic Acids by the Carboxylation of Grignard Reagents 750 19.12 Synthesis of Carboxylic Acids by the Preparation and Hydrolysis of Nitriles 752 19.13 Reactions of Carboxylic Acids: A Review and a Preview 753 19.14 Mechanism of Acid-Catalyzed Esterification 754 19.15 Intramolecular Ester Formation: Lactones 758 19.16 Halogenation of Carboxylic Acids: The Hell–Volhard–Zelinsky Reaction 759 19.17 Decarboxylation of Malonic Acid and Related Compounds 760 19.18 Spectroscopic Analysis of Carboxylic Acids 763 19.19 SUMMARY 765 PROBLEMS 768 CHAPTER 20 CARBOXYLIC ACID DERIVATIVES: NUCLEOPHILIC ACYL SUBSTITUTION 774 20.1 Nomenclature of Carboxylic Acid Derivatives 775 20.2 Structure of Carboxylic Acid Derivatives 777 20.3 Nucleophilic Substitution in Acyl Chlorides 780 20.4 Preparation of Carboxylic Acid Anhydrides 783 20.5 Reactions of Carboxylic Acid Anhydrides 784 20.6 Sources of Esters 787 20.7 Physical Properties of Esters 788 20.8 Reactions of Esters: A Review and a Preview 790 20.9 Acid-Catalyzed Ester Hydrolysis 791 20.10 Ester Hydrolysis in Base: Saponification 794 20.11 Reaction of Esters with Ammonia and Amines 799 20.12 Thioesters 800 20.13 Preparation of Amides 800 20.14 Lactams 803 20.15 Imides 804 20.16 Hydrolysis of Amides 804 20.17 The Hofmann Rearrangement 807 Condensation Polymers: Polyamides and Polyesters 809 20.18 Preparation of Nitriles 813 20.19 Hydrolysis of Nitriles 815 20.20 Addition of Grignard Reagents to Nitriles 816