SIXTH EDITION

Organic Chemistry

Robert Thornton MorrisonRobert Neilson Boyd

New York University

Prentice Hall International, Inc.

Contents

Preface xxiiiAcknowledgments xxvii

PART ONEThe Fundamentals

1 Structure and Properties1.1 Organic chemistry 11.2 The structural theory 31.3 The chemical bond before 1926 41.4 Quantum mechanics 51.5 Atomic orbitals 61.6 Electronic configuration. Pauli exclusion principle 81.7 Molecular orbitals 91.8 The covalent bond 91.9 Hybrid orbitals: sp 111.10 Hybrid orbitals: sp2 131.11 Hybrid orbitals: sp3 151.12 Unshared pairs of electrons 171.13 Intramolecular forces 201.14 Bond dissociation energy. Homolysis and heterolysis 211.15 Polarity of bonds 231.16 Polarity of molecules 231.17 Structure and physical properties 261.18 Melting point 271.19 Intermolecular forces 281.20 Boiling point 301.21 Solubility 31

vi CONTENTS

1.22 Acids and bases 331.23 Isomerism 36

2 Methane Energy of Activation. Transition State2.1 Hydrocarbons 392.2 Structure of methane 402.3 Physical properties 412.4 Source 412.5 Reactions 422.6 Oxidation. Heat of combustion 422.7 Chlorination: a substitution reaction 432.8 Control of chlorination 442.9 Reaction with other halogens: halogenation 442.10 Relative reactivity 452.11 Reaction mechanisms 452.12 Mechanism of chlorination. Free radicals 462.13 Chain reactions 482.14 Inhibitors 492.15 Heat of reaction 502.16 Energy of activation 572.17 Progress of reaction: energy changes 522.18 Rate of reaction 552.19 Relative rates of reaction 582.20 Relative reactivities of halogens toward methane 592.21 An alternative mechanism for halogenation 612.22 Structure of the methyl radical, sp2 Hybridization 642.23 Transition state 652.24 Reactivity and development of the transition state 672.25 Chlorofluorocarbons and the ozone shield 692.26 Molecular formula: its fundamental importance 722.27 Qualitative elemental analysis 722.28 Quantitative elemental analysis: carbon, hydrogen, and

halogen 732.29 Empirical formula 742.30 Molecular weight. Molecular formula 74

3 Alkenes Free-Radical Substitution3.1 Classification by structure: the family 773.2 Structure of ethane 783.3 Free rotation about the carbon-carbon single bond.

Conformations. Torsional strain 793.4 Propane and the butanes 833.5 Conformations of n-butane. Van der Waals repulsion 553.6 Higher alkanes. The homologous series 863.7 Nomenclature 873.8 Alkyl groups 883.9 Common names of alkanes 903.10 IUPAC names of alkanes 90

CONTENTS vii

3.11 Classes of carbon atoms and hydrogen atoms 923.12 Physical properties 923.13 Industrial source 943.14 Industrial source vs. laboratory preparation 963.15 Preparation 973.16 The Grignard reagent: an organometallic compound 993.17 Coupling of alkyl halides with organometallic compounds 1013.18 Reactions 1023.19 Halogenation 1043.20 Mechanism of halogenation 1063.21 Orientation of halogenation 7073.22 Relative reactivities of alkanes toward halogenation 7093.23 Ease of abstraction of hydrogen atoms. Energy of activation 7703.24 Stability of free radicals 7773.25 Ease of formation of free radicals 7753.26 Transition state for halogenation 7753.27 Orientation and reactivity 1143.28 Reactivity and selectivity 7753.29 Non-rearrangement of free radicals. Isotopic tracers 7763.30 Combustion 1183.31 The greenhouse effect 7793.32 Pyrolysis: cracking 7203.33 Determination of structure 7273.34 Analysis of alkanes 722

4 Stereochemistry I. Stereoisomers4.1 Stereochemistry and stereoisomerism 7254.2 Isomer number and tetrahedral carbon 7264.3 Optical activity. Plane-polarized light 1284.4 The polarimeter 7254.5 Specific rotation 7294.6 Enantiomerism: the discovery 7504.7 Enantiomerism and tetrahedral carbon 7574.8 Enantiomerism and optical activity 7554.9 Prediction of enantiomerism. Chirality 7554.10 The chiral center 7554.11 Enantiomers 7564.12 The racemic modification 7554.13 Optical activity: a closer look 7594.14 Configuration 1404.15 Specification of configuration: 7? and S 1404.16 Sequence rules 1414.17 Diastereomers 1444.18 Meso structures 1464.19 Specification of configuration: more than one chiral center 1484.20 Conformational isomers 1494.21 Reactions involving stereoisomers 7504.22 Generation of a chiral center. Synthesis and optical activity 757

viii CONTENTS

4.23 Reactions of chiral molecules. Bond-breaking 7554.24 Reactions of chiral molecules. Relating configurations 1544.25 Optical purity 7564.26 Reactions of chiral molecules. Generation of a second chiral

center 7564.27 Reactions of chiral molecules with optically active reagents.

Resolution 7554.28 Reactions of chiral molecules. Mechanism of free-radical

chlorination 760

5 Alkyl Halides Nucleophilic Aliphatic Substitution5.1 Homolytic and heterolytic chemistry 7655.2 Relative rates of competing reactions 7665.3 Structure. The functional group 7675.4 Classification and nomenclature 7655.5 Physical properties 7695.6 Preparation 7705.7 Reactions. Nucleophilic aliphatic substitution 7725.8 Nucleophilic aliphatic substitution. Nucleophiles and leaving

groups 7755.9 Rate of reaction: effect of concentration. Kinetics 7775.10 Kinetics of nucleophilic aliphatic substitution. Second-order and

first-order reactions 7755.11 Nucleophilic aliphatic substitution: duality of mechanisms 7 795.12 The SN2 reaction: mechanism and kinetics 7575.13 The SN2 reaction: stereochemistry. Inversion of

configuration 7525.14 The SN2 reaction: reactivity. Steric hindrance 7555.15 The SNI reaction: mechanism and kinetics. Rate-determining

step 7555.16 Carbocations 7975.17 Structure of carbocations 7955.18 The SNI reaction: stereochemistry 1945.19 Relative stabilities of carbocations 7965.20 Stabilization of carbocations. Accommodation of charge. Polar

effects 7995.21 The SNI reaction: reactivity. Ease of formation of

carbocations 2005.22 Rearrangement of carbocations 2035.23 SN2 VS. SNI 2055.24 Analysis of alkyl halides 277

6 Alcohols and Ethers6.1 Introduction 2756.2 Structure of alcohols 2746.3 Classification of alcohols 2146.4 Nomenclature of alcohols 2756.5 Physical properties of alcohols 275

CONTENTS ix

6.6 Industrial source 2756.7 Fermentation of carbohydrates 2796.8 Fuel from carbohydrates. Carbon dioxide balance 2796.9 Ethanol 2276.10 Preparation of alcohols 2226.11 Reactions of alcohols 2246.12 Alcohols as acids and bases 2276.13 Reaction of alcohols with hydrogen halides. Acid catalysis 2296.14 Formation of alkyl sulfonates 2336.15 Oxidation of alcohols 235

ETHERS

6.16 Structure and nomenclature of ethers 23 76.17 Physical properties of ethers 2556.18 Industrial sources of ethers. Dehydration of alcohols 2556.19 Preparation of ethers 2406.20 Preparation of ethers. Williamson synthesis 2416.21 Reactions of ethers. Cleavage by acids 2426.22 Analysis of alcohols 2436.23 Analysis of ethers 244

7 Role of the Solvent Secondary Bonding7.1 Role of the solvent 2497.2 Secondary bonding 2507.3 Solubility: non-ionic solutes 2527.4 Solubility: ionic solutes. Protic and aprotic solvents. Ion pairs 2547.5 The SNI reaction: role of the solvent. Ion-dipole bonds 2557.6 The SN2 reaction: role of the solvent. Protic and aprotic

solvents 2677.7 The SN2 reaction: phase-transfer catalysis 2647.8 SN2 VS. SNI: effect of the solvent 2677.9 Solvolysis. Nucleophilic assistance by the solvent 2657.10 The medium: a message 277

8 Alkenes I. Structure and Preparation Elimination8.1 Unsaturated hydrocarbons 2738.2 Structure of ethylene. The carbon-carbon double bond 2738.3 Propylene 2768.4 Hybridization and orbital size 2768.5 The butylenes 2778.6 Geometric isomerism 2798.7 Higher alkenes 2528.8 Names of alkenes 2528.9 Physical properties 2558.10 The organic chemistry of vision 2558.11 Industrial source 2578.12 Preparation 2578.13 Dehydrohalogenation of alkyl halides: 1,2-elimination 2908.14 Kinetics of dehydrohalogenation. Duality of mechanism 293

CONTENTS

8.15 The E2 mechanism 2948.16 Evidence for the E2 mechanism. Kinetics and absence of

rearrangements 2948.17 Evidence for the E2 mechanism. Isotope effects 2958.18 Evidence for the E2 mechanism. Absence of hydrogen

exchange 2978.19 Evidence for the E2 mechanism. The element effect 2998.20 The E2 reaction: orientation and reactivity 3008.21 The El mechanism 3038.22 Evidence for the El mechanism 3048.23 The El reaction: orientation 3068.24 Elimination: E2 vs. El 5058.25 Elimination vs. substitution 5058.26 Dehydration of alcohols 570

Alkenes II. Reactions of the Carbon-Carbon Double BondElectrophilic and Free-Radical Addition9.1 Reactions of alkenes 5779.2 Reactions at the carbon-carbon double bond. Addition 5779.3 Hydrogenation. Heat ofhydrogenation 3239.4 Heat ofhydrogenation and stability of alkenes 3269.5 Addition of hydrogen halides. Markovnikov's rule. Regioselective

reactions 3279.6 Addition of hydrogen bromide. Peroxide effect 3309.7 Addition of sulfuric acid 5579.8 Addition of water. Hydration 3329.9 Electrophilic addition: mechanism 3329.10 Electrophilic addition: rearrangements 3349.11 Electrophilic addition: orientation and reactivity 3359.12 Addition of halogens 3399.13 Mechanism of addition of halogens 3409.14 Halohydrin formation: addition of the elements of hypohalous

acids 3429.15 Addition of alkenes. Dimerization 3439.16 Addition of alkanes. Alkylation 3449.17 Oxymercuration-demercuration 3469.18 Hydroboration-oxidation 3479.19 Orientation of hydroboration 3489.20 Mechanism of hydroboration 3499.21 Free-radical addition. Mechanism of the peroxide-initiated

addition of HBr 5579.22 Orientation of free-radical addition 3529.23 Other free-radical additions 3559.24 Free-radical polymerization of alkenes 3569.25 Hydroxylation. Formation of 1,2-diols 3579.26 Cleavage: determination of structure by degradation.

Ozonolysis 5559.27 Analysis of alkenes 360

CONTENTS xi

10 Stereochemistry II. Stereoselective and StereospecificReactions10.1 Organic chemistry in three dimensions 36710.2 Stereochemistry of addition of halogens to alkenes. syn- and anti-

addition 36810.3 Mechanism of addition of halogens to alkenes 5 7210.4 Stereochemistry of the E2 reaction, syn- and a/jri-elimination 37710.5 Stereospecific reactions 55710.6 Stereoselectivity vs. stereospecificity 55210.7 A look ahead 555

11 Conjugation and Resonance Dienes11.1 The carbon-carbon double bond as a substituent 55711.2 Free-radical halogenation of alkenes: substitution vs.

addition 55511.3 Free-radical substitution in alkenes: orientation and

reactivity 39011.4 Free-radical substitution in alkenes: allylic rearrangement 39211.5 Symmetry of the allyl radical 39311.6 The theory of resonance 39411.7 The allyl radical as a resonance hybrid 39511.8 Stability of the allyl radical 39711.9 Orbital picture of the allyl radical 39711.10 Using the resonance theory 39911.11 Resonance stabilization of alkyl radicals. Hyperconjugation 40711.12 The allyl cation as a resonance hybrid 40211.13 Nucleophilic substitution in allylic substrates: SNI . Reactivity.

Allylic rearrangement 40411.14 Stabilization of carbocations: the resonance effect 40611.15 Nucleophilic substitution in allylic substrates: SN2 40711.16 Nucleophilic substitution in vinylic substrates. Vinylic

cations 40711.17 Dienes: structure and properties 40911.18 Stability of conjugated dienes 47011.19 Resonance in conjugated dienes 41111.20 Resonance in alkenes. Hyperconjugation 41311.21 Ease of formation of conjugated dienes: orientation of

elimination 41411.22 Electrophilic addition to conjugated dienes. 1,4-Addition 41411.23 1,2- vs. 1,4-Addition. Rate vs. equilibrium 41711.24 Free-radical polymerization of dienes. Rubber and rubber

substitutes 41911.25 Isoprene and the isoprene rule 42111.26 Analysis of dienes 421

12 Alkynes12.1 Introduction 42512.2 Structure of acetylene. The carbon-carbon triple bond 42512.3 Higher alkynes. Nomenclature 428

xii CONTENTS

12.4 Physical properties of alkynes 42512.5 Industrial source of acetylene 42912.6 Preparation of alkynes 42912.7 Reactions of alkynes 43012.8 Reduction of alkenes 43312.9 Electrophilic addition to alkynes 43412.10 Hydration of alkynes. Tautomerism 43512.11 Acidity of alkynes. Very weak acids 43612.12 Reactions of metal acetylides. Synthesis of alkynes 43812.13 Formation of carbon-carbon bonds. Role played by

organometallic compounds 43912.14 Analysis of alkynes 440

13 Cyclic Aliphatic Compounds13.1 Open-chain and cyclic compounds 44313.2 Nomenclature 44313.3 Industrial source 44613.4 Preparation 44713.5 Reactions 44813.6 Reactions of small-ring compounds. Cyclopropane and

cyclobutane 44913.7 Baeyer strain theory 45013.8 Heats of combustion and relative stabilities of the

cycloalkanes 45013.9 Orbital picture of angle strain 45313.10 Factors affecting stability of conformations 45413.11 Conformations of cycloalkanes 45513.12 Equatorial and axial bonds in cyclohexane 46013.13 Stereoisomerism of cyclic compounds: cis and trans isomers 46313.14 Stereoisomerism of cyclic compounds. Conformational

analysis 46613.15 Stereochemistry of elimination from alicyclic compounds 47113.16 Carbenes. Methylene. Cycloaddition 47313.17 Addition of substituted carbenes. 1,1-Elimination 47613.18 Cyclic ethers 47813.19 Crown ethers. Host-guest relationship 47813.20 Epoxides. Structure and preparation 48113.21 Reactions of epoxides 45213.22 Acid-catalyzed cleavage of epoxides. awfr'-Hydroxylation 45513.23 Base-catalyzed cleavage of epoxides 45513.24 Orientation of cleavage of epoxides 45513.25 Analysis of alicyclic compounds 457

14 Aromaticity Benzene

14.1 Aliphatic and aromatic compounds 49314.2 Structure of benzene 49414.3 Molecular formula. Isomer number. Kekule structure 49414.4 Stability of the benzene ring. Reactions of benzene 497

CONTENTS xiii

14.5 Stability of the benzene ring. Heats of hydrogenation andcombustion 495

14.6 Carbon-carbon bond lengths in benzene 49914.7 Resonance structure of benzene 50014.8 Orbital picture of benzene 50714.9 Representation of the benzene ring 50314.10 Aromatic character. The Huckel 4n + 2 rule 50414.11 Nomenclature of benzene derivatives 50514.12 Polynuclear aromatic hydrocarbons. Naphthalene 57014.13 Quantitative elemental analysis: nitrogen and sulfur 575

75 Electrophilic Aromatic Substitution15.1 Introduction 57715.2 Effect of substituent groups 57915.3 Determination of orientation 52015.4 Determination of relative reactivity 52715.5 Classification of substituent groups 52215.6 Orientation in disubstituted benzenes 52215.7 Orientation and synthesis 52415.8 Mechanism of nitration 52515.9 Mechanism of sulfonation 52 715.10 Mechanism of Friedel-Crafts alkylation 52515.11 Mechanism of halogenation 52915.12 Desulfonation. Mechanism of protonation 52915.13 Mechanism of electrophilic aromatic substitution: a

summary 53015.14 Mechanism of electrophilic aromatic substitution: the two

steps 55715.15 Reactivity and orientation 53515.16 Theory of reactivity 53615.17 Theory of orientation 55515.18 Electron release via resonance 54015.19 Effect of halogen on electrophilic aromatic substitution 54215.20 Relation to other carbocation reactions 54415.21 Electrophilic substitution in naphthalene 545

16 Aromatic-Aliphatic Compounds Arenes and TheirDerivatives16.1 The aromatic ring as a substituent 54916.2 Aromatic-aliphatic hydrocarbons: arenes 54916.3 Structure and nomenclature of arenes and their derivatives 55716.4 Physical properties 55216.5 Industrial source of alkylbenzenes 55516.6 Preparation of alkylbenzenes 55616.7 Friedel-Crafts alkylation 55716.8 Mechanism of Friedel-Crafts alkylation 55516.9 Limitations of Friedel-Crafts alkylation 56716.10 Reactions of alkylbenzenes 567

xiv CONTENTS

16.11 Oxidation of alkylbenzenes 56316.12 Electrophilic aromatic substitution in alkylbenzenes 56416.13 Halogenation of alkylbenzenes: ring vs. side chain 56516.14 Side-chain halogenation of alkylbenzenes 56616.15 Resonance stabilization of the benzyl radical 56516.16 Triphenylmethyl: a stable free radical 5 7016.17 Stability of the benzyl cation 57416.18 Nucleophilic substitution in benzylic substrates 57516.19 Preparation of alkenylbenzenes. Conjugation with the ring 57616.20 Reactions of alkenylbenzenes 57816.21 Addition to conjugated alkenylbenzenes 57916.22 Alkynylbenzenes 55016.23 Analysis of arenes 580

17 Spectroscopy and Structure17.1 Determination of structure: spectroscopic methods 55517.2 The mass spectrum 55617.3 The electromagnetic spectrum 58917.4 The infrared spectrum 59017.5 Infrared spectra of hydrocarbons 59217.6 Infrared spectra of alcohols 594\1.1 Infrared spectra of ethers 59617.8 The ultraviolet spectrum 59717.9 The nuclear magnetic resonance (NMR) spectrum 60017.10 NMR. Number of signals. Equivalent and non-equivalent

protons 60717.11 NMR. Positions of signals. Chemical shift 60417.12 NMR. Peak area and proton counting 60917.13 NMR. Splitting of signals. Spin-spin coupling 67017.14 NMR. Coupling constants 62017.15 NMR. Complicated spectra. Deuterium labeling 62317.16 Equivalence of protons: a closer look 62517.17 Carbon-13 NMR (CMR) spectroscopy 62917.18 CMR. Splitting 63017.19 CMR. Chemical shift 63417.20 NMR and CMR spectra of hydrocarbons 63917.21 NMR and CMR spectra of alkyl halides 64017.22 NMR and CMR spectra of alcohols and ethers. Hydrogen

bonding. Proton exchange 64017.23 The electron spin resonance (ESR) spectrum 642

18 Aldehydes and Ketones Nucleophilic Addition18.1 Structure 65718.2 Nomenclature 65518.3 Physical properties 66018.4 Preparation 66718.5 Preparation of ketones by Friedel-Crafts acylation 6668.6 Preparation of ketones by use of organocopper compounds 665

CONTENTS xv

18.7 Reactions. Nucleophilic addition 66918.8 Oxidation 67518.9 Reduction 67718.10 Addition of cyanide 67518.11 Addition of derivatives of ammonia 6 7918.12 Addition of alcohols. Acetal formation 65018.13 Cannizzaro reaction 65518.14 Addition of Grignard reagents 65518.15 Products of the Grignard synthesis 65618.16 Planning a Grignard synthesis 65518.17 Syntheses using alcohols 69218.18 Limitations of the Grignard synthesis 69518.19 Tetrahydropyranyl (THP) ethers: the use of a protecting

group 69618.20 Analysis of aldehydes and ketones 69718.21 Iodoformtest 69718.22 Analysis of 1,2-diols. Periodic acid oxidation 69918.23 Spectroscopic analysis of aldehydes and ketones 700

19 Carboxylic Acids19.1 Structure 77519.2 Nomenclature 77419.3 Physical properties 77719.4 Salts of carboxylic acids 77519.5 Industrial source 77919.6 Preparation 72019.7 Grignard synthesis 72319.8 Nitrile synthesis 72419.9 Reactions 72519.10 Ionization of carboxylic acids. Acidity constant 72919.11 Equilibrium 73019.12 Acidity of carboxylic acids 73219.13 Structure of carboxylate ions 73319.14 Effect of substituents on acidity 73519.15 Conversion into acid chlorides 73 719.16 Conversion into esters 73719.17 Conversion into amides 74019.18 Reduction of acids to alcohols 74019.19 Halogenation of aliphatic acids. Substituted acids 74719.20 Dicarboxylic acids 74219.21 Analysis of carboxylic acids. Neutralization equivalent 74419.22 Spectroscopic analysis of carboxylic acids 745

20 Functional Derivatives of Carboxylic Acids NucleophilicAcyl Substitution20.1 Structure 75320.2 Nomenclature 75420.3 Physical properties 754

xvi CONTENTS

20.4 Nucleophilic acyl substitution. Role of the carbonyl group 75520.5 Nucleophilic substitution: alkyl vs. acyl 759

ACID CHLORIDES

20.6 Preparation of acid chlorides 76020.7 Reactions of acid chlorides 76720.8 Conversion of acid chlorides into acid derivatives 762

ACID ANHYDRIDES

20.9 Preparation of acid anhydrides 76320.10 Reactions of acid anhydrides 764

AMIDES

20.11 Preparation of amides 76620.12 Reactions of amides 76620.13 Hydrolysis of amides 76720.14 Imides 767

ESTERS

20.15 Preparation of esters 76520.16 Reactions of esters 77020.17 Alkaline hydrolysis of esters 77320.18 Acidic hydrolysis of esters 77620.19 Ammonolysis of esters 77520.20 Transesterification 77520.21 Reaction of esters with Grignard reagents 77920.22 Reduction of esters 75020.23 Functional derivatives of carbonic acid 75020.24 Analysis of carboxylic acid derivatives. Saponification

equivalent 75420.25 Spectroscopic analysis of carboxylic acid derivatives 755

21 Carbanions I Aldol and Claisen Condensations21.1 Acidity of a-hydrogens 79 721.2 Reactions involving carbanions 79921.3 Base-promoted halogenation of ketones 50221.4 Acid-catalyzed halogenation of ketones. Enolization 50421.5 Aldol condensation 50521.6 Dehydration of aldol products 50721.7 Use of aldol condensation in synthesis 50521.8 Crossed aldol condensation 50921.9 Reactions related to the aldol condensation 57021.10 The Wittig reaction 57721.11 Claisen condensation. Formation of/i-keto esters 57521.12 Crossed Claisen condensation 576

22 Amines I. Preparation and Physical Properties22.1 Structure 52722.2 Classification 52722.3 Nomenclature 52222.4 Physical properties of amines 52522.5 Salts of amines 525

CONTENTS xvii

22.6 Stereochemistry of nitrogen 52522.7 Industrial source 52722.8 Preparation 52522.9 Reduction of nitro compounds 55222.10 Ammonolysis of halides 55222.11 Reductive amination 55422.12 Hofmann degradation of amides 55622.13 Synthesis of secondary and tertiary amines 83622.14 Heterocyclic amines 55722.15 Hofmann rearrangement. Migration to electron-deficient

nitrogen 55522.16 Hofmann rearrangement. Stereochemistry at the migrating

group 54022.17 Hofmann rearrangement. Timing of the steps 547

23 Amines II. Reactions23.1 Reactions 54523.2 Basicity of amines. Basicity constant 54923.3 Structure and basicity 55023.4 Effect of substituents on basicity of aromatic amines 55523.5 Quaternary ammonium salts. Hofmann elimination 55423.6 E2 elimination: Hofmann orientation. The variable E2 transition

state 55523.7 Conversion of amines into substituted amides 55723.8 Ring substitution in aromatic amines 56023.9 Sulfonation of aromatic amines. Dipolar ions 56223.10 Sulfanilamide. The sulfa drugs 86323.11 Reactions of amines with nitrous acid 56423.12 Diazonium salts. Preparation and reactions 56623.13 Diazonium salts. Replacement by halogen. Sandmeyer

reaction 56923.14 Diazonium salts. Replacement by —CN. Synthesis of carboxylic

acids 57023.15 Diazonium salts. Replacement by —OH. Synthesis of

phenols 57023.16 Diazonium salts. Replacement by —H 57723.17 Syntheses using diazonium salts 57723.18 Coupling of diazonium salts. Synthesis of azo compounds 87323.19 Analysis of amines. Hinsberg test 57623.20 Analysis of substituted amides 87723.21 Spectroscopic analysis of amines and substituted amides 577

24 Phenols24.1 Structure and nomenclature 55924.2 Physical properties 59024.3 Salts of phenols 59524.4 Industrial source 59524.5 Rearrangement of hydroperoxides. Migration to electron-

deficient oxygen 595

xviii CONTENTS

24.6 Rearrangement of hydroperoxides. Migratory aptitude 59624.7 Preparation 59524.8 Reactions 59924.9 Acidity of phenols 90324.10 Ester formation. Fries rearrangement 90524.11 Ring substitution 90624.12 Kolbe reaction. Synthesis of phenolic acids 90524.13 Reimer-Tiemann reaction. Synthesis of phenolic aldehydes.

Dichlorocarbene 90524.14 Formation of aryl ethers 90924.15 Reactions of aryl ethers 97724.16 Analysis of phenols 97224.17 Spectroscopic analysis of phenols 972

25 Carbanions II Malonic Ester and Acetoacetic Ester Syntheses25.1 Carbanions in organic synthesis 92325.2 Malonic ester synthesis of carboxylic acids 92425.3 Acetoacetic ester synthesis of ketones 92725.4 Decarboxylation of /?-keto acids and malonic acids 93025.5 Direct and indirect alkylation of esters and ketones 95725.6 Synthesis of acids and esters via 2-oxazolines 93225.7 Organoborane synthesis of acids and ketones 93325.8 Alkylation of carbonyl compounds via enamines 935

PART TWOSpecial Topics

26 Aryl Halides Nucleophilic Aromatic Substitution26.1 Structure 94326.2 Physical properties 94426.3 Preparation 94626.4 Reactions 94526.5 Low reactivity of aryl and vinyl halides 94926.6 Structure of aryl and vinyl halides 95026.7 Nucleophilic aromatic substitution: bimolecular

displacement 95226.8 Bimolecular displacement mechanism for nucleophilic aromatic

/ substitution 95526.9 Reactivity in nucleophilic aromatic substitution 95626.10 Orientation in nucleophilic aromatic substitution 95726.11 Electron withdrawal by resonance 95526.12 Evidence for the two steps in bimolecular displacement 95926.13 Nucleophilic substitution: aliphatic and aromatic 96726.14 Elimination-addition mechanism for nucleophilic aromatic

substitution. Benzyne 96226.15 Analysis of aryl halides 96 7

CONTENTS xix

27 a,/?-Unsaturated Carbonyl Compounds Conjugate Addition27.1 Structure and properties 97727.2 Preparation 97327.3 Interaction of functional groups 97421A Electrophilic addition 97427.5 Nucleophilic addition 97627.6 Comparison of nucleophilic and electrophilic addition 97527.7 The Michael addition 97927.8 The Diels-Alder reaction 95227.9 Quinones 954

28 Molecular Orbitals. Orbital Symmetry28.1 Molecular orbital theory 99728.2 Wave equations. Phase 99228.3 Molecular orbitals. LCAO method 99328.4 Bonding and antibonding orbitals 99428.5 Electronic configurations of some molecules 99628.6 Aromatic character. The Huckel 4« + 2 rule 700028.7 Orbital symmetry and the chemical reaction 700428.8 Electrocyclic reactions 700528.9 Cycloaddition reactions 707528.10 Sigmatropic reactions 7079

29 Symphoria Neighboring Group Effects. Catalysis byTransition Metal Complexes29.1 Symphoria 705729.2 Neighboring group effects: the discovery. Stereochemistry 705229.3 Neighboring group effects: intramolecular nucleophilic

attack 705529.4 Neighboring group effects: rate of reaction. Anchimeric

assistance 705729.5 Homogeneous hydrogenation. Transition metal complexes 7 04229.6 Stereochemistry of homogeneous hydrogenation:

diastereoselectivity 704629.7 Stereochemistry of homogeneous hydrogenation:

enantioselectivity 704929.8 The oxo process 705229.9 Enzyme action 7054

30 Heterocyclic Compounds30.1 Heterocyclic systems 7057

FIVE-MEMBERED RINGS30.2 Structure of pyrrole, furan, and thiophene 705930.3 Source of pyrrole, furan, and thiophene 706730.4 Electrophilic substitution in pyrrole, furan, and thiophene.

Reactivity and orientation 7062

xx CONTENTS

30.5 Saturated five-membered heterocycles 7065SIX-MEMBERED RINGS

30.6 Structure of pyridine 706630.7 Source of pyridine compounds 706730.8 Reactions of pyridine 706530.9 Electrophilic substitution in pyridine 706530.10 Nucleophilic substitution in pyridine 706930.11 Basicity of pyridine 707730.12 Reduction of pyridine 7075

31 Macromolecules. Polymers and Polymerization31.1 Macromolecules 707731.2 Polymers and polymerization 707531.3 Free-radical vinyl polymerization 705031.4 Copolymerization 705531.5 Ionic polymerization. Living polymers 7 05431.6 Coordination polymerization 705731.7 Step-reaction polymerization 709031.8 Structure and properties of macromolecules 7 095

32 Stereochemistry III. Enantiotopic and Diastereotopic Ligandsand Faces32.1 Introduction 770732.2 Biological oxidation and reduction. Ethanol and

acetaldehyde 770732.3 Biological oxidation and reduction. Deuterium labeling

experiments 770532.4 Biological oxidation and reduction. Stereochemistry 770432.5 Enantiotopic and diastereotopic ligands 770732.6 Enantiotopic and diastereotopic faces 777032.7 Origin of enantiospecificity 7772

PART THREEBiomolecules

33 Lipids Fats and Steroids33.1 The organic chemistry of biomolecules 777933.2 Lipids 772033.3 Occurrence and composition of fats 772033.4 Hydrolysis of fats. Soap. Micelles 772433.5 Fats as sources of pure acids and alcohols 772533.6 Detergents 772633.7 Unsaturated fats. Hardening of oils. Drying oils 772733.8 Phosphoglycerides. Phosphate esters 772533.9 Phospholipids and cell membranes 7750

CONTENTS xxi

33.10 Biosynthesis of fatty acids 775233.11 Steroids 7754

34 Carbohydrates I. Monosaccharides34.1 Introduction 774534.2 Definition and classification 774434.3 (+)-Glucose: an aldohexose 774434.4 (—)-Fructose: a 2-ketohexose 774634.5 Stereoisomers of (+)-glucose. Nomenclature of aldose

derivatives 774634.6 Oxidation. Effect of alkali 774934.7 Osazone formation. Epimers 775734.8 Lengthening the carbon chain of aldoses. The Kiliani-Fischer

synthesis 775234.9 Shortening the carbon chain of aldoses. The Ruff

degradation 775434.10 Conversion of an aldose into its epimer 775434.11 Configuration of (+)-glucose. The Fischer proof 775534.12 Configurations of aldoses 776034.13 Optical families, D and L 776234.14 Tartaricacid 776434.15 Families of aldoses. Absolute configuration 776634.16 Cyclic structure of D-(+)-glucose. Formation of glucosides 776534.17 Configuration about C-1 77 7534.18 Methylation 777434.19 Determination of ring size 777634.20 Conformation 7775

35 Carbohydrates II. Disaccharides and Polysaccharides35.1 Disaccharides 775535.2 (+)-Maltose 775535.3 (+)-Cellobiose 775535.4 (+)-Lactose 775935.5 (+)-Sucrose 779735.6 Polysaccharides 779235.7 Starch 779535.8 Structure of amylose. End group analysis 779535.9 Structure of amylopectin 779535.10 Cyclodextrins 779535.11 Structure of cellulose 720035.12 Reactions of cellulose 7200

36 Proteins and Nucleic Acids Molecular Biology36.1 Proteins 720536.2 Structure of amino acids 720636.3 Amino acids as dipolar ions 720536.4 Isoelectric point of amino acids 7277

xxii CONTENTS

36.5 Configuration of natural amino acids 727236.6 Preparation of amino acids 727536.7 Reactions of amino acids 727536.8 Peptides. Geometry of the peptide linkage 727536.9 Determination of structure of peptides. Terminal residue

analysis. Partial hydrolysis 727736.10 Synthesis of peptides 722736.11 Proteins. Classification and function. Denaturation 722536.12 Structure of proteins 722636.13 Peptide chain 722636.14 Side chains. Isoelectric point. Electrophoresis 722736.15 Conjugated proteins. Prosthetic groups. Coenzymes 722536.16 Secondary structure of proteins 722936.17 Biochemistry, molecular biology, and organic chemistry 725536.18 Mechanism of enzyme action. Chymotrypsin 725636.19 Nucleoproteins and nucleic acids 724736.20 Chemistry and heredity. The genetic code 7246

Suggested Readings 1251

Answers to Problems 1263

Index 1279