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