MISTRYF O U R T H E D I T I O N

K. Peter C. VollhardtUniversity of California at Berkeley

NeilE. SchoreUniversity of California at Davis

III. H. FREEMHN flND COMPANYNew York

ce: A User's Guide to Organic Chemistry: Structure and Function xxi

CHRPTER 1 Structure and Bonding in Organic Molecules1-1 The Scope of Organic Chemistry: An Overview1-2 Coulomb Forces: A Simplified View of Bonding1-3 Ionic and Covalent Bonds: The Octet Rule1-4 Electron-Dot Model of Bonding: Lewis Structures1-5 Resonance Forms1-6 Atomic Orbitals: A Quantum Mechanical Description

of Electrons around the Nucleus1-7 Molecular Orbitals and Covalent Bonding1-8 Hybrid Orbitals: Bonding in Complex Molecules1-9 Structures and Formulas of Organic Molecules

The Big PictureChapter Integration Problems / Important Concepts /

Problems / Team Problems / Preprofessional Problems

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CHAPTER 2 Structure and Reactivity: Reids and Bases, Polar andHonpolar Molecules

2-1 Kinetics and Thermodynamics of Simple Chemical Processes2-2 Acids and Bases; Electrophiles and Nucleophiles i2-3 Functional Groups: Centers of Reactivity2-4 Straight-Chain and Branched Alkanes2-5 Naming the Alkanes2-6 Structural and Physical Properties of Alkanes2-7 ' Rotation about Single Bonds: Conformations2-8 Rotation in Substituted Ethanes

The Big PictureChapter Integration Problems / Important Concepts /

Problems / Team Problems / Preprofessional Problems

CHAPTER 3

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Reactions of fllkanes: Bond-Dissociation Energies, RadicalHalogenation, and Relative Reactivity 93

3-1 Strength of Alkane Bonds: Radicals 943-2 Structure of Alkyl Radicals: Hyperconjugation 973-3 Conversion of Petroleum: Pyrolysis 983-4 Cnlorination of Methane: The Radical Chain Mechanism 101

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3-5 Other Radical Halogenations of Methane 1073-6 Chlorination of Higher Alkanes: Relative Reactivity

and Selectivity3-7 Selectivity in Radical Halogenation with Fluorine and Bromine3-8 Synthetic Radical Halogenation3-9 Synthetic Chlorine Compounds and the Stratospheric

Ozone Layer 1163-10 Combustion and the Relative Stabilities of Alkanes 119

The Big Picture 121Chapter Integration Problems / Important Concepts / Problems /

Team Problems / Preprofessional Problems 121

CHRPTER 4 Cyclic Alkanes4-1 Names and Physical Properties of Cycloalkanes 1294-2 Ring Strain and the Structure of Cycloalkanes 1314-3 Cyclohexane: A Strain-Free Cycloalkane 1354-4 Substituted Cyclohexanes 1404-5 Larger Cycloalkanes 1444-6 Poly cyclic Alkanes 1454-7 Carbocyclic Products in Nature 147

The Big Picture , 153Chapter Integration Problems / Important Concepts / Problems /

Team Problems / Preprofessional Problems 153

CHRPTER 5 Steieoisomers 1635-1 Chiral Molecules 1655-2 Optical Activity , 1695-3 Absolute Configuration: R—S Sequence Rules 1725-4 Fischer Projections 1775-5 Molecules Incorporating Several Stereocenters:

Diastereomers 1815-6 Meso Compounds 1855-7 Stereochemistry in Chemical Reactions 1875-8 Resolution: Separation of Enantiomers 195

The Big Picture 197Chapter Integration Problems / Important Concepts / Problems /

Team Problems / Preprofessional Problems 198

CHAPTER 6 Properties and Reactions of Haloalkanes:Bimolecular Kucleophilic Substitution 209

6-1 Physical Properties of Haloalkanes 2096-2 Nucleophilic Substitution 2126-3 Reaction Mechanisms Involving Polar Functional Groups:

Using "Electron-Pushing" Arrows 214

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6-4 A Closer Look at the Nucelophilic Substitution Mechanism:Kinetics 216

6-5 Frontside or Backside Attack? Stereochemistry of theSN2 Reaction 219

6-6 Consequences of Inversion in SN2 Reactions 2216-7 Structure and SN2 Reactivity: The Leaving Group 2236-8 Structure and SN2 Reactivity: The Nucleophile 2256-9 Structure and SN2 Reactivity: The Substrate 231

The Big Picture 236Chapter Integration Problems / Important Concepts / Problems /

Team Problems / Preprofessional Problems 236

CHRPTER 7 Further Reactions of Haloalkanes: UnimoleculaiSubstitution and Pathways of Elimination 243

7-1 Solvolysis of Tertiary and Secondary Haloalkanes 2437-2 Unimolecular Nucleophilic Substitution 2457-3 Stereochemical Consequences of SN1 Reactions 2487-4 Effects of Solvent, Leaving Group, and Nucleophile on

Unimolecular Substitution 2497-5 Effect of the Alkyl Group on the SN1 Reaction: Carbocation Stability 2517-6 Unimolecular Elimination: El 2547-7 Bimolecular Elimination: E2 2577-8 Competition between Substitution and Elimination:

Structure Determines Function 2607-9 Summary of Reactivity of Haloalkanes 263

The Big Picture 264Chapter Integration Problems / Important Concepts / Problems /

Team Problems / Preprofessional Problems 265

CHAPTER B Hydroxy Functional Group: Alcohols:Properties, Preparation, and Strategy of Synthesis 276

8-1 Naming the Alcohols 2778-2 Structural and Physical Properties of Alcohols 2788-3 Alcohols as Acids and Bases 2818-4 Industrial Sources of Alcohols: Carbon Monoxide and Ethene 2848-5 Synthesis of Alcohols by Nucleophilic Substitution 2858-6 Synthesis of Alcohols: Oxidation-Reduction Relation between

Alcohols and Carbonyl Compounds 2868-7 Organometallic Reagents: Sources of Nucleophilic Carbon for

Alcohol Synthesis 2938-8 Organometallic Reagents in the Synthesis of Alcohols 2978-9 Complex Alcohols: An Introduction to Synthetic Strategy 299

The Big Picture 306Chapter Integration Problems / Important Concepts / Problems /

Team Problems / Preprofessional Problems 307

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CHAPTER ? Further Reactions of Alcohols and the Chemistry of Ethers 3219-1 Reactions of Alcohols with Base: Preparation of Alkoxides 3229-2 Reactions of Alcohols with Strong Acids: Alkyloxonium Ions

in Substitution and Elimination Reactions of Alcohols 3239-3 Carbocation Rearrangements 3269-4 Organic and Inorganic Esters from Alcohols 3319-5 Names and Physical Properties of Ethers 3349-6 Williamson Ether Synthesis 3379-7 Synthesis of Ethers: Alcohols and Mineral Acid 3429-8 Reactions of Ethers 3449-9 Reactions of Oxacyclopropanes 3469-10 Sulfur Analogs of Alcohols and Ethers 3519-11 Physiological Properties and Uses of Alcohols and Ethers 354

The Big Picture 358Chapter Integration Problems / Important Concepts / Problems /

Team Problems / Preprofessional Problems 358

CHRPTER 10 Using Nuclear Magnetic Resonance Spectroscopyto Deduce Structure 374

10-1 Physical and Chemical Tests 37510-2 Defining Spectroscopy 37510-3 Proton Nuclear Magnetic Resonance 37810-4 Using NMR Spectra to Analyze Molecular Structure:

The Proton Chemical Shift 38310-5 Tests for Chemical Equivalence 38710-6 Integration 39110-7 Spin-Spin Splitting: The Effect of Nonequivalent

Neighboring Hydrogens 39310-8 Spin-Spin Splitting: Some Complications 40110-9 Carbon-13 Nuclear Magnetic Resonance 408

The Big Picture 417Chapter Integration Problems / Important Concepts / Problems /

Team Problems / Preprofessional Problems 417

CHAPTER 11 Hlkenes and Infrared Spectroscopy 43111-1 Naming the Alkenes 43211-2 Structure and Bonding in Ethene: The Pi Bond 43511-3 Physical Properties of Alkenes 43811-4 Nuclear Magnetic Resonance of Alkenes 43911-5 Infrared Spectroscopy 44411-6 Degree of Unsaturation: Another Aid to Identifying

Molecular Structure 44911-7 Catalytic Hydrogenation of Alkenes: Relative Stability

of Double Bonds 451

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11-8 Preparation of Alkenes from Haloalkenes and Alkyl Sulfonates:Bimolecular Elimination Revisited 453

11-9 Preparation of Alkenes by Dehydration of Alcohols 457The Big Picture 459Chapter Integration Problems / Important Concepts / Problems /

Team Problems / Preprofessional Problems 460

CHAPTER 12 Reactions of Rlkenes 47412-1 Why Addition Reactions Proceed: Thermodynamic Feasibility 47512-2 Catalytic Hydrogenation 47512-3 Nucleophilic Character of the Pi Bond: Electrophilic Addition

of Hydrogen Halides 47912-4 Alcohol Synthesis by Electrophilic Hydration:

Thermodynamic Control 48312-5 Electrophilic Addition of Halogens to Alkenes 48512-6 The Generality of Electrophilic Addition 48812-7 Oxymercuration-Demercuration: A Special

Electrophilic Addition 49112-8 Hydroboration-Oxidation: A Stereospecific

Anti-Markovnikov Hydration 49412-9 Diazomethane, Carbenes, and Cyclopropane Synthesis 49612-10 Oxacyclopropane (Epoxide) Synthesis: Epoxidation by

Peroxycarboxylic Acids 49812-11 Vicinal Syn Dihydroxylation with Osmium Tetroxide 50112-12 Oxidative Cleavage: Ozonolysis 50312-13 Radical Additions: Anti-Markovnikov Product Formation 50512-14 Dimerization, Oligomerization, and Polymerization

of Alkenes 50712-15 Synthesis of Polymers 50812-16 Ethene: An Important Industrial Feedstock ' 51412-17 Alkenes in Nature: Insect Pheromones 514

The Big Picture 516Chapter Integration Problems / Important Concepts / Problems /

Team Problems / Preprofessional Problems 516

CHRPTER 13 fllkynes: The Carbon-Carbon Triple Bond 53313-1 Naming the Alkynes 53413-2 Properties and Bonding in the Alkynes 53513-3 Spectroscopy of the Alkynes 53713-4 Preparation of Alkynes by Double Elimination 54113-4 Preparation of Alkynes from Alkynyl Anions 54213-6 Reduction of Akynes: The Relative Reactivity of the

Two Pi Bonds 543,' 13-7 Electrophilic Addition Reactions of Alkynes 547

Anti-Markovnikov Additions to Triple Bonds 550

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13-9 Chemistry of Alkenyl Halides 55113-10 Ethyne as an Industrial Starting Material . 55213-11 Naturally Occurring and Physiologically Active Alkynes 554

The Big Picture 555Chapter Integration Problems / Important Concepts / Problems /

Team Problems / Preprofessional Problems 556

CHAPTER 14 Delocalized Pi Systems: Inuestigation by Ultraviolet andVisible Spectroscopy 570

14-1 Overlap of Three Adjacent p Orbitals: Electron Delocalizationin the 2-Propenyl (Allyl) System 571

14-2 Radical Ally lie Halogenation 57414-3 Nucleophilic Substitution of Allylic Halides: SN1 and SN2 57514-4 Allylic Organometallic Reagents: Useful Three-Carbon

Nucleophiles 57714-5 Two Neighboring Double Bonds: Conjugated Dienes 57814-6 Electrophilic Attack on Conjugated Dienes: Kinetic and

Thermodynamic Control 58214-7 Delocalization Among More than Two Pi Bonds: Extended

Conjugation and Benzene 58514-8 A Special Transformation of Conjugated Dienes:

Diels-Alder Cycloaddition 58714-9 Electrocyclic Reactions 59614-10 Polymerization of Conjugated Dienes: Rubber 60214-11 Electronic Spectra: Ultraviolet and Visible Spectroscopy 606

The Big Picture 610Chapter Integration Problems / Important Concepts / Problems /

Team Problems / Preprofessional Problems 611

INTERLUDE: A Summary of Organic Reaction Mechanisms 623

CHRPT

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Q J Q | Benzene and Hromaticity: Electrophilic AromaticSubstitution

Naming the BenzenesStructure and Resonance Energy of Benzene:

A First Look at AromaticityPi Molecular Orbitals of BenzeneSpectral Characteristics of the Benzene RingPolycyclic Aromatic HydrocarbonsOther Cyclic Polyenes: Hiickel's RuleHiickel's Rule and Charged MoleculesSynthesis of Benzene Derivatives: Electrophilic

Aromatic SubstitutionHalogenation of Benzene: The Need for a CatalystNitration and Sulfonation of Benzene

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15-11 Friedel-Crafts Alkylation 66115-12 Limitations of Friedel-Crafts Alkylations 66315-13 Friedel-Crafts Alkanoylation (Acylation) 665

The Big Picture 669Chapter Integration Problems / Important Concepts / Problems /

Team Problems / Preprofessional Problems 669

CHAPTER I f Electrophilic Attack on Derivatives of Benzene:Substituents Control Regioselectivity 681

16-1 Activation or Deactivation by Substituents on aBenzene Ring • 682

16-2 Directing Inductive Effects of Alkyl Groups 68416-3 Directing Effects of Substituents in Conjugation with

the Benzene Ring 68816-4 Electrophilic Attack on Disubstituted Benzenes 69516-5 Synthetic Strategies toward Substituted Benzenes 69816-6 Reactivity of Polycyclic Benzenoid Hydrocarbons 70316-7 Polycyclic Aromatic Hydrocarbons and Cancer 706

The Big Picture 708Chapter Integration Problems / Important Concepts / Problems /

Team Problems / Preprofessional Problems 708

CHAPTER 17 Aldehydes and Ketones: The Carbonyl Group 72117-1 Naming the Aldehydes and Ketones 72217-2 Structure of the Carbonyl Group 72417-3 Spectroscopic Properties of Aldehydes and Ketones 72617-4 Preparation of Aldehydes and Ketones 72817-5 Reactivity of the Carbonyl Group: Mechanisms i

of Addition 73117-6 Addition of Water to Form Hydrates 73317-7 Addition of Alcohols to Form Hemiacetals

and Acetals 73517-8 Acetals as Protecting Groups 73717-9 Nucleophilic Addition of Ammonia and

Its Derivatives 74017-10 Deoxygenation of the Carbonyl Group 74417-11 Addition of Hydrogen Cyanide to Give Cyanohydrins 74617-12 Addition of Phosphorus Ylides: The Wittig Reaction 74717-13 Oxidation by Peroxycarboxylic Acids:

The Baeyer-Villiger Oxidation 75117-14 Oxidative Chemical Tests for Aldehydes 752

The Big Picture 753Chapter Integration Problems / Important Concepts / Problems /

Team Problems / Preprofessional Problems 753

X Contents

CHAPTER 18 Enols, Enolates, and the Aldol Condensation:a,j3-Unsaturated Aldehydes and Ketones 769

18-1 Acidity of Aldehydes and Ketones: Enolate Ions 77018-2 Keto-Enol Equilibria 77118-3 Halogenation of Aldehydes and Ketones 77418-4 Alkylation of Aldehydes and Ketones 77618-5 Attack by Enolates on the Carbonyl Function: Aldol Condensation 77918-6 Crossed Aldol Condensation 78418-7 Intramolecular Aldol Condensation 785 |18-8 Properties of a,/3-Unsaturated Aldehydes and Ketones 788 f18-9 Conjugate Additions to a,/3-Unsaturated Aldehydes and Ketones 790 |18-10 1,2-and 1,4-Additions of Organometallic Reagents 792 I18-11 Conjugate Additions of Enolate Ions: Michael Addition and

Robinson Annulation 795The Big Picture 797Chapter Integration Problems / Important Concepts / Problems /

Team Problems / Preprofessional Problems 798

CHAP?EJll% Carboxylic Acids 81319-1 Naming the Carboxylic Acids 81419-2 Structural and Physical Properties of Carboxylic Acids 81519-3 NMR and IR Spectroscopy of Carboxylic Acids 81819-4 Acidic and Basic Character of Carboxylic Acids 82019-5 Carboxylic Acid Synthesis in Industry 82319-6 Methods for Introducing the Carboxy Functional Group 82319-7 Substitution at the Carboxy Carbon:

The Addition-Elimination Mechanism 82719-8 Carboxylic Acid Derivatives: Alkanoyl (Acyl) Halides

and Anhydrides 82919-9 Carboxylic Acid Derivatives: Esters 83219-10 Carboxylic Acid Derivatives: Amides 83519-11 Reduction of Carboxylic Acids by Lithium Aluminum Hydride 83719-12 Bromination Next to the Carboxy Group:

The Hell-Volhard-Zelinsky Reaction 83719-13 Biological Activity of Carboxylic Acids 839

The Big Picture 846Chapter Integration Problems / Important Concepts / Problems /

Team Problems / Preprofessional Problems 846

CHAPTER20 urboxylic flcid Deriuatiues and Mass Spectrometry 86420-1 Relative Reactivities, Structures, and Spectra of

Carboxylic Acid Derivatives 86520-2 Chemistry of Alkanoyl Halides 86920-3 Chemistry of Carboxylic Anhydrides 873

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20-4 Chemistry of Esters 87420-5 Esters in Nature: Waxes, Fats, Oils, and Lipids 88020-6 Amides: The Least Reactive Carboxylic Acid Derivatives 88220-7 Amidates and Their Halogenation: The Hofmann

Rearrangement 88720-8 Alkanenitriles: A Special Class of Carboxylic

Acid Derivatives 89020-9 Measuring the Molecular Weight of Organic Compounds:

Mass Spectrometry 89420-10 Fragmentation Patterns of Organic Molecules 89920-11 High-Resolution Mass Spectrometry 904

The Big Picture 907Chapter Integration Problems / Important Concepts / Problems /

Team Problems / Preprofessional Problems 907

CHAPTER 21 Amines and Their Derivatives:Functional Groups Containing Nitrogen

21-1 Naming the Amines21-2 Structural and Physical Properties of Amines21-3 Spectroscopy of the Amine Group21-4 Acidity and Basicity of Amines21-5 Synthesis of Amines by Alkylation21-6 Synthesis of Amines by Reductive Animation21-7 Synthesis of Amines from Carboxylic Acids21-8 Quaternary Ammonium Salts: Hofmann Elimination21-9 Mannich Reaction: Alkylation of Enols by Iminium Ions21-10 Nitrosation of Amines

The Big PictureChapter Integration Problems / Important Concepts / Problems /

Team Problems / Preprofessional Problems

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CHRPTER 22 Chemistry of Benzene Substituents:Alkylbenzenes, Phenols, and Benzenamines

22-1 Reactivity at the Phenylmethyl (Benzyl) Carbon:Benzylic Resonance Stabilization

22-2 Benzylic Oxidations and Reductions22-3 Names and Properties of Phenols22-4 Preparation of Phenols: Nucleophilic Aromatic Substitution22-5 Alcohol Chemistry of Phenols22-6 Electrophilic Substitution of Phenols22-7 An Electrocyclic Reaction of the Benzene Ring:

The Claisen Rearrangement22-8 Oxidation of Phenols: Cyclohexadienediones (Benzoquinones)22-9 Oxidation-Reduction Processes in Nature22-10 'Arenediazonium Salts

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22-11 Electrophilic Substitution with Arenediazonium Salts:Diazo Coupling 1006

The Big Picture 1008Chapter Integration Problems / Important Concepts / Problems /

Team Problems / Preprofessional Problems 1008

CHAPTER 23 Enolates and the Claisen Condensation: Synthesisof /3-Dicaibonyl Compounds; Acyl Anion Equivalents 1024

23-1 /3-Dicarbonyl Compounds: Claisen Condensations 102523-2 /3-Dicarbonyl Compounds as Synthetic Intermediates 103123-3 /3-Dicarbonyl Anion Chemistry: Michael Additions 103623-4 Alkanoyl (Acyl) Anion Equivalents: Preparation of

a-Hydroxyketones 1038The Big Picture 1044Chapter Integration Problems / Important Concepts / Problems /

Team Problems / Preprofessional Problems 1044

CHAPTER 24 Carbohydrates: Polyfunctional Compounds in Nature 105624-1 Names and Structures of Carbohydrates 105724-2 Conformations and Cyclic Forms of Sugars 106124-3 Anomers of Simple Sugars: Mutarotation of Glucose 106524-4 Polyfunctional Chemistry of Sugars: Oxidation to

Carboxylic Acids 106624-5 Oxidative Cleavage of Sugars 106824-6 Reduction of Monosaccharides to Alditols 107024-7 Carbonyl Condensations with Amine Derivatives 107024-8 Ester and Ether Formation: Glycosides 107124-9 Step-by-Step Buildup and Degradation of Sugars 107524-10 Relative Configurations of the Aldoses: An Exercise in

Structure Determination 107924-11 Complex Sugars in Nature: Disaccharides 108124-12 Polysaccharides and Other Sugars in Nature 1086

The Big Picture 1091Chapter Integration Problem / Important Concepts / Problems /

Team Problems / Preprofessional Problems 1091

CHAPTEA 25 Heterocycles: Heteroatoms in Cyclic Organic Compounds 110425-1 Naming the Heterocycles 110725-2 Nonaromatic Heterocycles 110825-3 Structure and Properties of Aromatic Heterocyclopentadienes 111225-4 Reactions of the Aromatic Heterocyclopentadienes 111425-5 Structure and Preparation of Pyridine: An Azabenzene 111825-6 Reactions of Pyridine 112125-7 Quinoline and Isoquinoline: The Benzopyridines 1124

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25-8 Alkaloids: Physiologically Potent Nitrogen Heterocyclesin Nature 1125

The Big Picture 1130Chapter Integration Problems / Important Concepts / Problems /

Team Problems /Preprofessional Problems 1131

CHAPTER 26 Amino Acids, Peptides, Proteins, and Nucleic Acids:Nitrogen-Containing Polymers in Nature 1147

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26-1 Structure and Properties of Amino Acids 114826-2 Synthesis of Amino Acids: A Combination of Amine and

Carboxylic Acid Chemistry 115426-3 Synthesis of Enantiomerically Pure Amino Acids 115626-4 Peptides and Proteins: Amino Acid Oligomers and Polymers 115826-5 Determination of Primary Structure: Amino Acid Sequencing 116726-6 Synthesis of Polypeptides: A Challenge in the Application

of Protecting Groups 117226-7 Merrifield Solid-Phase Peptide Synthesis 117526-8 Polypeptides in Nature: Oxygen Transport by the Proteins

Myoglobin and Hemoglobin 117726-9 Biosynthesis of Proteins: Nucleic Acids 117926-10 Protein Synthesis Through RNA 118426-11 DNA Sequencing and Synthesis: Cornerstones

of Gene Technology 1186The Big Picture 1191Chapter Integration Problems / Important Concepts / Problems /

Team Problems / Preprofessional Problems 1192

MCAT® Questions MCAT®-1

i Answers to Exercises < A-l

Photograph Credits C-l

Index 1-1