ORGANIC CHEMISTRY

Fifth Edition

Stanley H. Pine Professor of Chemistry California State University, Los Angeles

McGraw-Hill, Inc. New York St. Louis San Francisco Auckland Bogota Caracas Lisbon London Madrid Mexico Milan Montreal New Delhi Paris San Juan Singapore Sydney Tokyo Toronto

Contents

1 What is Organic Chemistry? 1

1-1 The Chemistry of Carbon Compounds 2 1-2 A Historical Perspective 3 1-3 Contemporary Organic Chemistry 6

2 Bonding in Organic Molecules 8

2-1 Bonding 9 2-2 Structural Formulas of Organic Molecules 12 2-3 Electronegativity and Dipoles 22 2-4 Quantum Mechanics and Atomic Orbitals 26 2-5 Molecular Orbitals and Bonding 30 2-6 Hybrid Orbitals 33 2-7 Bond Angles 36 2-8 Bond Energies and Distances 41 2-9 Summary 45 2-10 Supplementary Problems 46

3 Classes and Nomenclature of Organic Compounds— Functional Groups 48

3-1 Hydrocarbons 49 3-2 Heteroatom Functional Groups 65 3-3 Supplementary Problems 89

ix

X Contents

4 Characteristic Reactions of Organic Compounds 93

4-1 Acids and Bases 94 4-2 Reactions of Organic Compounds 105 4-3 Oxidation and Reduction 110 4-4 Summary 113 4-5 Supplementary Problems 113

5 Reaction Mechanism 116

5-1 The Reaction Mechanism 117 5-2 Reaction Energetics 122 5-3 Reaction Kinetics 127 5-4 Summary 129 5-5 Supplementary Problems 130

6 The Shapes of Molecules—Stereochemistry 132

6-1 Representations of Three-Dimensional Molecules 133 6-2 Conformations of Acyclic Compounds 137 6-3 Conformations of Cyclic Compounds 140 6-4 Geometrical Isomerism 152 6-5 Chirality and Optical Activity 163 6-6 Summary 177 6-7 Supplementary Problems 178

7 Structural Effects on Reactivity—Resonance 182

7-1 Structural Effects on Acidity and Basicity 183 7-2 The Resonance Method 190 7-3 Aromatic Compounds 195 7-4 Some Consequences of Resonance 198 7-5 Summary 208 7-6 Supplementary Problems 209

8 Nucleophilic Additions to the Carbonyl Group— Aldehydes and Ketones 212

8-1 Reactivity of the Carbonyl Group 213 8-2 Cyanide as the Nucleophile—The Cyanohydrin Reaction 219 8-3 Oxygen or Sulfur as the Nucleophile—Acetals, Ketals and Hydrates

223

Contents x i

8-4 Hydride as the Nucleophüe—Reduction 231 8-5 Carbon as the Nucleophüe—Organometallic Compounds 239 8-6 Nitrogen as the Nucleophüe 248 8-7 Nucleophilic Addition to Carbonyl Analogs 253 8-8 Summary 255 8-9 Supplementary Problems 259

9 Nucleophilic Substitutions on the Carbonyl Group—The Carboxylic Acid Family 265

9-1 Reactivity in the Carboxylic Acid Family 267 9-2 Oxygen or Sulfur as the Nucleophüe—Esters and Carboxylic Acids

270 9-3 Nitrogen as the Nucleophüe—Amides 283 9-4 Acyl Halides and Anhydrides 286 9-5 Hydride as the Nucleophüe—Reduction 291 9-6 Carbon as the Nucleophüe—Organometallic Reagents 295 9-7 Enantiomer Resolution 301 9-8 Nucleophilic Substitution on Derivatives of Sulfuric and Phosphoric

Acids 302 9-9 Summary 308 9-10 Supplementary Problems 312

10 Nucleophilic Substitutions at Saturated Carbon 316

10-1 The Reaction Mechanism 317 10-2 Stereochemistry of Nucleophilic Substitution 322 10-3 The Variables in Nucleophilic Substitution 327 10-4 Summary 343 10-5 Supplementary Problems 345

11 The Scope of Nucleophilic Substitution 348

11-1 Nucleophüe—Substrate Combinations 349 11-2 Halide as the Nucleophüe—Haloalkanes 351 11-3 Competing Reactions 356 11-4 Oxygen and Sulfur as the Nucleophiles—Alcohols, Ethers, and

Sulfides 359 11-5 Nitrogen and Phosphorus as the Nucleophiles—Amines 372 11-6 Neighboring Group Participation 379 11-7 Hydride, Nitrile, and Organometallic Nucleophiles 383 11-8 Summary 389 11-9 Supplementary Problems 391

XÜ Contents

12 The Alpha Carbanion—Nucleophilic-Electrophilic Reactivity of Carbonyl Compounds 398

12-1 Enols and Enolate Anions 399 12-2 Addition-Dehydration—The Aldol Reaction 404 12-3 Ester Condensation 411 12-4 Fragmentation of Beta-Dicarbonyl Compounds 418 12-5 Alkylation of Enolate Anions 421 12-6 Other Stabilized Carbanions and Carbon Nucleophiles 430 12-7 Summary 433 12-8 Supplementary Problems 435

13 Nucleophilic Additions and Substitutions in Synthesis 444

13-1 Available Reactions 445 13-2 Experimental Considerations 446 13-3 The Strategy of Synthesis 448 13-4 Synthesis Examples 452 13-5 Summary 456 13-6 Supplementary Problems 457

14 Elimination Reactions—Alkenes and Alkynes 464

14-1 The Reaction Mechanism 466 14-2 Elimination Versus Substitution 471 14-3 The Direction of Elimination 475 14-4 Stereochemistry 479 14-5 Formation of Alkenes 486 14-6 Formation of Alkynes 499 14-7 Other Double and Triple Bonds 501 14-8 Summary 506 14-9 Supplementary Problems 509

15 Electrophilic Additions to Unsaturated Carbon 517

15-1 The Mechanism of Electrophilic Addition 519 15-2 Direction and Stereochemistry of Addition 522 15-3 Additions to Alkenes and Alkynes 525 15-4 Transition Metal Organometallics 557 15-5 Summary 565 15-6 Supplementary Problems 569

Contents x i ü

16 Additions to Conjugated Compounds 576

16-1 Conjugated Dienes 577 16-2 Double Bonds Conjugated with Carbonyl Groups 582 16-3 Pericyclic Reactions 588 16-4 Summary 603 16-5 Supplementary Problems 604

17 The Mechanism of Electrophilic Aromatic Substitution 609

17-1 Characteristics of Cyclic Polyenes 610 17-2 Mechanism and Orientation in Electrophilic Aromatic Substitution

616 17-3 Quantitative Correlations of Substituent Effects 629 17-4 Summary 635 17-5 Supplementary Problems 636

18 The Scope oi Aromatic Substitutions 638

18-1 Electrophilic Aromatic Substitution Reactions—Heteroatoms as the Electrophiles 639

18-2 Electrophilic Aromatic Substitution Reactions—Carbon Electrophiles 650

18-3 Nucleophilic Aromatic Substitutions 662 18-4 Synthesis with Aromatic Compounds 673 18-5 Summary 682 18-6 Supplementary Problems 686

19 Polycyclic and Heterocyclic Aromatic Compounds 693

19-1 Polycyclic Aromatic Compounds 694 19-2 Heterocyclic Aromatic Compounds 703 19-3 Summary 715 19-4 Supplementary Problems 716

20 Organic Synthesis 721

20-1 Design of a Synthesis 722 20-2 Reaction Patterns 728 20-3 Stereochemistry 741

Xiv Contents

20-4 Applications and Examples 744 20-5 Summary 753 20-6 Supplementary Problems 753

21 Carbohydrates and Nucleosides 757

21-1 Characteristics and Properties of Carbohydrates 758 21-2 Chemistry of Monosaccharides 764 21-3 Oligosaccharides and Polysaccharides 786 21-4 Nucleosides and Nucleotides 796 21-5 Sunlight, Carbohydrates, and Energy 800 21-6 Summary 805 21-7 Supplementary Problems 807

22 Ämino Acids and Proteins 811

22-1 Amino Acids 812 22-2 Peptides 822 22-3 Proteins, Enzymes, and Biosynthesis 840 22-4 Summary 854 22-5 Supplementary Problems 855

23 Lipids 858

23-1 Glycerol Derivatives 859 23-2 Terpenes 866 23-3 Steroids 875 23-4 Prostaglandins 885 23-5 Pheromones 894 23-6 Summary 900 23-7 Supplementary Problems 901

24 Free Radicals 909

24-1 History 911 24-2 Characteristics of Free Radicals 912 24-3 Reactions 922 24-4 Detection of Free Radicals 937 24-5 Summary 939 24-6 Supplementary Problems 940

Contents XV

25 Natural and Synthetic Polymers 944

25-1 Structural Characteristics 945 25-2 Preparation of Synthetic Polymers 951 25-3 Fibers 963 25-4 Summary 969 25-5 Supplementary Problems 970

26 Molecular Rearrangements 972

26-1 Rearrangement to an Electron-Deficient Atom 973 26-2 Free-Radical and Anionic Rearrangements 995 26-3 Orbital Symmetry Considerations 1000 26-4 Summary 1014 26-5 Supplementary Problems 1015

27 Photochemistry and Electrochemistry 1021

27-1 Principles of Photochemistry 1023 27-2 Photochemical Reactions 1028 27-3 Principles of Electrochemistry 1042 27-4 Electrochemical Reactions 1046 27-5 Summary 1057 27-6 Supplementary Problems 1057

APPENDIX: Spectroscopic Methods 1062

A-l Electromagnetic Radiation 1064 A-2 Nuclear Magnetic Resonance Spectroscopy 1065 A-3 Infrared Spectroscopy 1095 A-4 Ultraviolet and Visible Spectroscopy 1113 A-5 Mass Spectrometry 1120 A-6 Spectroscopic Solution of Structural Problems 1132 A-7 Supplementary Problems 1139

Index 1157