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CONTENTS List of Boxed Essays xxiii Preface xxv Acknowledgments xxviii A Guide to Using this Text xxxi INTRODUCTION1 The Origins of Organic Chemistry 1 Berzelius, W"hler, 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 STRUCTURE DETERMINES PROPERTIES7 1.1 Atoms, Electrons, and Orbitals 7 1.2 Ionic Bonds 10 1.3 Covalent Bonds and the Octet Rule 12 1.4 Double Bonds and Triple Bonds 14 1.5 Polar Covalent Bonds and Electronegativity 14 Electrostatic Potential Maps 16 1.6 Formal Charge 17 1.7 Structural Formulas of Organic Molecules 21 1.8 Constitutional Isomers 23 1.9 Resonance 24 Learning By Modeling 28 1.10 The Shapes of Some Simple Molecules 29 1.11 Molecular Dipole Moments 31 1.12 Acids and Bases: The Arrhenius View 32 1.13 Acids and Bases: The Bronsted-Lowry View 33 Curved Arrows 34 1.14 What Happened to pKb? 37 1.15 How Structure Affects Acid Strength 38 1.16 Acid-Base Equilibria 43 1.17 Lewis Acids and Lewis Bases 45 1.18 SUMMARY 47 Problems 50 HYDROCARBON FRAMEWORKS. ALKANES57 2.1 Classes of Hydrocarbons 57 2.2 Electron Waves and Chemical Bonds 58 2.3 Bonding in H2: The Valence Bond Model 60 2.4 Bonding in H2: The Molecular Orbital Model 61 2.5 Introduction to Alkanes: Methane, Ethane, and Propane 63 2.6 sp3 Hybridization and Bonding in Methane 63 Methane and the Biosphere 66 2.7 Bonding in Ethane 67 2.8 Isomeric Alkanes: The Butanes 67 2.9 Higher n-Alkanes 68 2.10 The C5H12 Isomers 69 2.11 IUPAC Nomenclature of Unbranched Alkanes 70 2.12 Applying the IUPAC Rules: The Names of the C6H14 Isomers 71 2.13 Alkyl Groups 73 2.14 IUPAC Names of Highly Branched Alkanes 75 2.15 Cycloalkane Nomenclature 77 A Brief History of Systematic Organic Nomenclature 78 2.16 Sources of Alkanes and Cycloalkanes 79 2.17 Physical Properties of Alkanes and Cycloalkanes 80 2.18 Chemical Properties. Combustion of Alkanes 83 Thermochemistry 86 2.19 Oxidation-Reduction in Organic Chemistry 87 2.20 sp2 Hybridization and Bonding in Ethylene 89 2.21 sp Hybridization and Bonding in Acetylene 92 2.22 Which Theory of Chemical Bonding Is Best? 93 2.23 SUMMARY 95 Problems 99 CONFORMATIONS OF ALKANES AND CYCLOALKANES104 3.1 Conformational Analysis of Ethane 105 3.2 Conformational Analysis of Butane 109 3.3 Conformations of Higher Alkanes 110 Molecular Mechanics Applied to Alkanes and Cycloalkanes 111 3.4 The Shapes of Cycloalkanes: Planar or Nonplanar? 112 3.5 Small Rings: Cyclopropane and Cyclobutane 114 3.6 Cyclopentane 115 3.7 Conformations of Cyclohexane 116 3.8 Axial and Equatorial Bonds in Cyclohexane 117 3.9 Conformational Inversion (Ring Flipping) in Cyclohexane 119 3.10 Conformational Analysis of Monosubstituted Cyclohexanes 120 Enthalpy, Free Energy, and Equilibrium Constant 122 3.11 Disubstituted Cycloalkanes: Stereoisomers 124 3.12 Conformational Analysis of Disubstituted Cyclohexanes 125 3.13 Medium and Large Rings 129 3.14 Polycyclic Ring Systems 129 3.15 Heterocyclic Compounds 131 3.16 SUMMARY 132 Problems 136 ALCOHOLS AND ALKYL HALIDES142 4.1 Functional Groups 143 4.2 IUPAC Nomenclature of Alkyl Halides 144 4.3 IUPAC Nomenclature of Alcohols 145 4.4 Classes of Alcohols and Alkyl Halides 146 4.5 Bonding in Alcohols and Alkyl Halides 146 4.6 Physical Properties of Alcohols and Alkyl Halides: Intermolecular Forces 147 4.7 Preparation of Alkyl Halides from Alcohols and Hydrogen Halides 151 4.8 Mechanism of the Reaction of Alcohols with Hydrogen Halides 153 4.9 Potential Energy Diagrams for Multistep Reactions: The SN1 Mechanism 159 4.10 Structure, Bonding, and Stability of Carbocations 160 4.11 Effect of Alcohol Structure on Reaction Rate 162 4.12 Reaction of Primary Alcohols with Hydrogen Halides: The SN2 Mechanism 163 4.13 Other Methods for Converting Alcohols to Alkyl Halides 165 4.14 Halogenation of Alkanes 166 4.15 Chlorination of Methane 166 4.16 Structure and Stability of Free Radicals 167 4.17 Mechanism of Methane Chlorination 172 4.18 Halogenation of Higher Alkanes 173 From Bond Energies to Heats of Reaction 174 4.19 SUMMARY 178 Problems 182 STRUCTURE AND PREPARATION OF ALKENES: ELIMINATION REACTIONS187 5.1 Alkene Nomenclature 187 Ethylene 189 5.2 Structure and Bonding in Alkenes 190 5.3 Isomerism in Alkenes 192 5.4 Naming Stereoisomeric Alkenes by the E-Z Notational System 193 5.5 Physical Properties of Alkenes 196 5.6 Relative Stabilities of Alkenes 197 5.7 Cycloalkenes 200 5.8 Preparation of Alkenes: Elimination Reactions 202 5.9 Dehydration of Alcohols 202 5.10 Regioselectivity in Alcohol Dehydration: The Zaitsev Rule 204 5.11 Stereoselectivity in Alcohol Dehydration 205 5.12 The E1 and E2 Mechanisms of Alcohol Dehydration 206 5.13 Rearrangements in Alcohol Dehydration 208 5.14 Dehydrohalogenation of Alkyl Halides 211 5.15 The E2 Mechanism of Dehydrohalogenation of Alkyl Halides 214 5.16 Anti Elimination in E2 Reactions: Stereoelectronic Effects 216 5.17 The E1 Mechanism of Dehydrohalogenation of Alkyl Halides 217 5.18 SUMMARY 220 Problems 223 REACTIONS OF ALKENES: ADDITION REACTIONS230 6.1 Hydrogenation of Alkenes 230 6.2 Heats of Hydrogenation 231 6.3 Stereochemistry of Alkene Hydrogenation 234 6.4 Electrophilic Addition of Hydrogen Halides to Alkenes 235 6.5 Regioselectivity of Hydrogen Halide Addition: Markovnikov's Rule 236 6.6 Mechanistic Basis for Markovnikov's Rule 238 Rules, Laws, Theories, and the Scientific Method 239 6.7 Carbocation Rearrangements in Hydrogen Halide Addition to Alkenes 241 6.8 Free-Radical Addition of Hydrogen Bromide to Alkenes 242 6.9 Addition of Sulfuric Acid to Alkenes 245 6.10 Acid-Catalyzed Hydration of Alkenes 247 6.11 Hydroboration-Oxidation of Alkenes 250 6.12 Stereochemistry of Hydroboration-Oxidation 252 6.13 Mechanism of Hydroboration-Oxidation 252 6.14 Addition of Halogens to Alkenes 254 6.15 Stereochemistry of Halogen Addition 256 6.16 Mechanism of Halogen Addition to Alkenes: Halonium Ions 256 6.17 Conversion of Alkenes to Vicinal Halohydrins 259 6.18 Epoxidation of Alkenes 260 6.19 Ozonolysis of Alkenes 262 6.20 Introduction to Organic Chemical Synthesis 265 6.21 Reactions of Alkenes with Alkenes: Polymerization 266 Ethylene and Propene: The Most Important Industrial Organic Chemicals 269 6.22 SUMMARY 271 Problems 274 STEREOCHEMISTRY281 7.1 Molecular Chirality: Enantiomers 281 7.2 The Chirality Center 282 7.3 Symmetry in Achiral Structures 286 7.4 Optical Activity 287 7.5 Absolute and Relative Configuration 289 7.6 The Cahn-Ingold-Prelog R-S Notational System 290 7.7 Fischer Projections 293 7.8 Properties of Enantiomers 295 Chiral Drugs 296 7.9 Reactions That Create a Chirality Center 297 7.10 Chiral Molecules with Two Chirality Centers 300 7.11 Achiral Molecules with Two Chirality Centers 303 Chirality of Disubstituted Cyclohexanes 305 7.12 Molecules with Multiple Chirality Centers 306 7.13 Reactions That Produce Diastereomers 307 7.14 Resolution of Enantiomers 310 7.15 Stereoregular Polymers 312 7.16 Chirality Centers Other Than Carbon 314 7.17 SUMMARY 315 Problems 318 NUCLEOPHILIC SUBSTITUTION326 8.1 Functional Group Transformation by Nucleophilic Substitution 326 8.2 Relative Reactivity of Halide Leaving Groups 330 8.3 The SN2 Mechanism of Nucleophilic Substitution 330 8.4 Stereochemistry of SN2 Reactions 331 8.5 How SN2 Reactions Occur 333 8.6 Steric Effects in SN2 Reactions 334 8.7 Nucleophiles and Nucleophilicity 336 An Enzyme-Catalyzed Nucleophilic Substitution of an Alkyl Halide 339 8.8 The SN1 Mechanism of Nucleophilic Substitution 339 8.9 Carbocation Stability and SN1 Reaction Rates 341 8.10 Stereochemistry of SN1 Reactions 342 8.11 Carbocation Rearrangements in SN1 Reactions 344 8.12 Effect of Solvent on the Rate of Nucleophilic Substitution 345 8.13 Substitution and Elimination as Competing Reactions 348 8.14 Sulfonate Esters as Substrates in Nucleophilic Substitution 350 8.15 Looking Back: Reactions of Alcohols with Hydrogen Halides 354 8.16 SUMMARY 355 Problems 357 ALKYNES363 9.1 Sources of Alkynes 363 9.2 Nomenclature 364 9.3 Physical Properties of Alkynes 365 9.4 Structure and Bonding in Alkynes: sp Hybridization 365 Natural and "Designed" Enediyne Antibiotics 368 9.5 Acidity of Acetylene and Terminal Alkynes 368 9.6 Preparation of Alkynes by Alkylation of Acetylene and Terminal Alkynes 370 9.7 Preparation of Alkynes by Elimination Reactions 372 9.8 Reactions of Alkynes 374 9.9 Hydrogenation of Alkynes 374 9.10 Metal-Ammonia Reduction of Alkynes 376 9.11 Addition of Hydrogen Halides to Alkynes 377 9.12 Hydration of Alkynes 379 9.13 Addition of Halogens to Alkynes 381 9.14 Ozonolysis of Alkynes 381 9.15 SUMMARY 382 Problems 384 CONJUGATION IN ALKADIENES AND ALLYLIC SYSTEMS390 10.1 The Allyl Group 390 10.2 Allylic Carbocations 391 10.3 Allylic Free Radicals 395 10.4 Allylic Halogenation 396 10.5 Classes of Dienes 398 10.6 Relative Stabilities of Dienes 399 10.7 Bonding in Conjugated Dienes 400 10.8 Bonding in Allenes 402 10.9 Preparation of Dienes 404 10.10 Addition of Hydrogen Halides to Conjugated Dienes 405 10.11 Halogen Addition to Dienes 407 Diene Polymers 408 10.12 The Diels-Alder Reaction 409 10.13 The p Molecular Orbitals of Ethylene and 1,3-Butadiene 412 10.14 A p Molecular Orbital Analysis of the Diels-Alder Reaction 414 10.15 SUMMARY 415 Problems 418 ARENES AND AROMATICITY423 11.1 Benzene 424 11.2 Kekul, and the Structure of Benzene 424 Benzene, Dreams, and Creative Thinking 426 11.3 A Resonance Picture of Bonding in Benzene 427 11.4 The Stability of Benzene 428 11.5 An Orbital Hybridization View of Bonding in Benzene 430 11.6 The p Molecular Orbitals of Benzene 430 11.7 Substituted Derivatives of Benzene and Their Nomenclature 432 11.8 Polycyclic Aromatic Hydrocarbons 434 Carbon Clusters, Fullerenes, and Nanotubes 436 11.9 Physical Properties of Arenes 438 11.10 Reactions of Arenes: A Preview 438 11.11 The Birch Reduction 438 11.12 Free-Radical Halogenation of Alkylbenzenes 439 11.13 Oxidation of Alkylbenzenes 443 11.14 Nucleophilic Substitution in Benzylic Halides 444 11.15 Preparation of Alkenylbenzenes 446 11.16 Addition Reactions of Alkenylbenzenes 447 11.17 Polymerization of Styrene 449 11.18 Cyclobutadiene and Cyclooctatetraene 449 11.19 Hückel's Rule 451 11.20 Annulenes 454 11.21 Aromatic Ions 456 11.22 Heterocyclic Aromatic Compounds 460 11.23 Heterocyclic Aromatic Compounds and Hückel's Rule 462 11.24 SUMMARY 463 Problems 467 REACTIONS OF ARENES: ELECTROPHILIC AROMATIC SUBSTITUTION473 12.1 Representative Electrophilic Aromatic Substitution Reactions of Benzene 474 12.2 Mechanistic Principles of Electrophilic Aromatic Substitution 474 12.3 Nitration of Benzene 477 12.4 Sulfonation of Benzene 478 12.5 Halogenation of Benzene 480 12.6 Friedel-Crafts Alkylation of Benzene 481 12.7 Friedel-Crafts Acylation of Benzene 484 12.8 Synthesis of Alkylbenzenes by Acylation-Reduction 486 12.9 Rate and Regioselectivity in Electrophilic Aromatic Substitution 488 12.10 Rate and Regioselectivity in the Nitration of Toluene 489 12.11 Rate and Regioselectivity in the Nitration of (Trifluoromethyl)benzene 492 12.12 Substituent Effects in Electrophilic Aromatic Substitution:Activating Substituents 494 12.13 Substituent Effects in Electrophilic Aromatic Substitution: Strongly Deactivating Substituents 498 12.14 Substituent Effects in Electrophilic Aromatic Substitution: Halogens 500 12.15 Multiple Substituent Effects 502 12.16 Regioselective Synthesis of Disubstituted Aromatic Compounds 504 12.17 Substitution in Naphthalene 506 12.18 Substitution in Hetereocyclic Aromatic Compounds 507 12.19 SUMMARY 508 Problems 512 SPECTROSCOPY519 13.1 Principles of Molecular Spectroscopy: Electromagnetic Radiation 520 13.2 Principles of Molecular Spectroscopy: Quantized Energy States 521 13.3 Introduction to 1H NMRSpectroscopy 522 13.4 Nuclear Shielding and 1H Chemical Shifts 525 13.5 Effects of Molecular Structure on 1H Chemical Shifts 526 Ring Currents: Aromatic and Antiaromatic 530 13.6 Interpreting 1H NMRSpectra 532 13.7 Spin-Spin Splitting in 1H NMRSpectroscopy 535 13.8 Splitting Patterns: The Ethyl Group 538 13.9 Splitting Patterns: The Isopropyl Group 540 13.10 Splitting Patterns: Pairs of Doublets 541 13.11 Complex Splitting Patterns 543 13.12 1H NMRSpectra of Alcohols 544 13.13 NMR and Conformations 545 Magnetic Resonance Imaging 546 13.14 13C NMR Spectroscopy 547 13.15 13C Chemical Shifts 549 13.16 13C NMR and Peak Intensities 551 13.17 13C 1H Coupling 552 13.18 Using DEPT to Count Hydrogens Attached to 13C 553 Spectra by the Thousands 555 13.19 2D NMR: COSY and HETCOR 556 13.20 Infrared Spectroscopy 559 13.21 Ultraviolet-Visible (UV-VIS) Spectroscopy 565 13.22 Mass Spectrometry 567 GasChromatography, GC/MS, and MS/MS 572 13.23 Molecular Formula as a Clue to Structure 573 13.24 SUMMARY 575 Problems 578 ORGANOMETALLIC COMPOUNDS587 14.1 Organometallic Nomenclature 588 14.2 Carbon-Metal Bonds in Organometallic Compounds 588 14.3 Preparation of Organolithium Compounds 589 14.4 Preparation of Organomagnesium Compounds: Grignard Reagents 591 14.5 Organolithium and Organomagnesium Compounds as Bronsted Bases 592 14.6 Synthesis of Alcohols Using Grignard Reagents 594 14.7 Synthesis of Alcohols Using Organolithium Reagents 597 14.8 Synthesis of Acetylenic Alcohols 597 14.9 Retrosynthetic Analysis 598 14.10 Preparation of Tertiary Alcohols from Esters and Grignard Reagents 601 14.11 Alkane Synthesis Using Organocopper Reagents 602 14.12 An Organozinc Reagent for Cyclopropane Synthesis 604 14.13 Carbenes and Carbenoids 606 14.14 Transition Metal Organometallic Compounds 608 14.15 Ziegler-Natta Catalysis of Alkene Polymerization 610 An Organometallic Compound That Occurs Naturally: Coenzyme B12 611 14.16 SUMMARY 614 Problems 617 ALCOHOLS, DIOLS, AND THIOLS623 15.1 Sources of Alcohols 623 15.2 Preparation of Alcohols by Reduction of Aldehydes and Ketones 627 15.3 Preparation of Alcohols by Reduction of Carboxylic Acids and Esters 632 15.4 Preparation of Alcohols from Epoxides 632 15.5 Preparation of Diols 633 15.6 Reactions of Alcohols: A Review and a Preview 635 15.7 Conversion of Alcohols to Ethers 635 15.8 Esterification 638 15.9 Esters of Inorganic Acids 640 15.10 Oxidation of Alcohols 641 Economic and Environmental Factors in Organic Synthesis 644 15.11 Biological Oxidation of Alcohols 645 15.12 Oxidative Cleavage of Vicinal Diols 647 15.13 Thiols 648 15.14 Spectroscopic Analysis of Alcohols and Thiols 651 15.15 SUMMARY 653 Problems 657 ETHERS, EPOXIDES, AND SULFIDES665 16.1 Nomenclature of Ethers, Epoxides, and Sulfides 665 16.2 Structure and Bonding in Ethers and Epoxides 667 16.3 Physical Properties of Ethers 668 16.4 Crown Ethers 668 Polyether Antibiotics 670 16.5 Preparation of Ethers 671 16.6 The Williamson Ether Synthesis 672 16.7 Reactions of Ethers: A Review and a Preview 673 16.8 Acid-Catalyzed Cleavage of Ethers 674 16.9 Preparation of Epoxides: A Review and a Preview 676 16.10 Conversion of Vicinal Halohydrins to Epoxides 676 16.11 Reactions of Epoxides: A Review and a Preview 678 16.12 Nucleophilic Ring-Opening of Epoxides 679 16.13 Acid-CatalyzedRing-Opening of Epoxides 681 16.14 Epoxides in Biological Processes 684 16.15 Preparation of Sulfides 685 16.16 Oxidation of Sulfides: Sulfoxides and Sulfones 685 16.17 Alkylation of Sulfides: Sulfonium Salts 686 16.18 Spectroscopic Analysis of Ethers, Epoxides, and Sulfides 688 16.19 SUMMARY 691 Problems 695 ALDEHYDES AND KETONES: NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP 703 17.1 Nomenclature 703 17.2 Structure and Bonding: The Carbonyl Group 706 17.3 Physical Properties 708 17.4 Sources of Aldehydes and Ketones 709 17.5 Reactions of Aldehydes and Ketones: A Review and a Preview 712 17.6 Principles of Nucleophilic Addition: Hydration of Aldehydes and Ketones 712 17.7 Cyanohydrin Formation 717 17.8 Acetal Formation 720 17.9 Acetals as Protecting Groups 723 17.10 Reaction with Primary Amines: Imines 724 17.11 Reaction with Secondary Amines: Enamines 727 Imines in Biological Chemistry 728 17.12 The Wittig Reaction 730 17.13 Planning an Alkene Synthesis via the Wittig Reaction 732 17.14 Stereoselective Addition to Carbonyl Groups 734 17.15 Oxidation of Aldehydes 736 17.16 Baeyer-Villiger Oxidation of Ketones 736 17.17 Spectroscopic Analysis of Aldehydes and Ketones 738 17.18 SUMMARY 741 Problems 745 ENOLS AND ENOLATES755 18.1 The a-Carbon Atom and Its Hydrogens 756 18.2 a Halogenation of Aldehydes and Ketones 757 18.3 Mechanism of a Halogenation of Aldehydes and Ketones 757 18.4 Enolization and Enol Content 759 18.5 Stabilized Enols 761 18.6 Base-Catalyzed Enolization. Enolate Anions 763 18.7 The Haloform Reaction 765 The Haloform Reaction and the Biosynthesis of Trihalomethanes 767 18.8 Some Chemical and Stereochemical Consequences of Enolization 768 18.9 The Aldol Condensation 769 18.10 Mixed Aldol Condensations 774 18.11 Effects of Conjugation in a,b-Unsaturated Aldehydes and Ketones 775 18.12 Conjugate Addition to a,b-Unsaturated Carbonyl Compounds 777 18.13 Addition of Carbanions to a,b-Unsaturated Ketones: The Michael Reaction 779 18.14 Conjugate Addition of Organocopper Reagents to a,b-Unsaturated Carbonyl Compounds 780 18.15 Alkylation of Enolate Anions 781 18.16 SUMMARY 781 Problems 784 CARBOXYLIC ACIDS791 19.1 Carboxylic Acid Nomenclature 792 19.2 Structure and Bonding 793 19.3 Physical Properties 794 19.4 Acidity of Carboxylic Acids 795 19.5 Salts of Carboxylic Acids 797 Quantitative Relationships Involving Carboxylic Acids 798 19.6 Substituents and Acid Strength 801 19.7 Ionization of Substituted Benzoic Acids 803 19.8 Dicarboxylic Acids 804 19.9 Carbonic Acid 804 19.10 Sources of Carboxylic Acids 806 19.11 Synthesis of Carboxylic Acids by the Carboxylation of Grignard Reagents 806 19.12 Synthesis of Carboxylic Acids by the Preparation and Hydrolysis of Nitriles 808 19.13 Reactions of Carboxylic Acids: A Review and a Preview 809 19.14 Mechanism of Acid-Catalyzed Esterification 810 19.15 Intramolecular Ester Formation: Lactones 814 19.16 a Halogenation of Carboxylic Acids: The Hell-Volhard-Zelinsky Reaction 19.17 Decarboxylation of Malonic Acid and Related Compounds 816 19.18 Spectroscopic Analysis of Carboxylic Acids 819 19.19 SUMMARY 821 Problems 824 CARBOXYLIC ACID DERIVATIVES: NUCLEOPHILIC ACYL SUBSTITUTION830 20.1 Nomenclature of Carboxylic Acid Derivatives 831 20.2 Structure and Reactivity of Carboxylic Acid Derivatives 833 20.3 General Mechanism for Nucleophilic Acyl Substitution 836 20.4 Nucleophilic Substitution in Acyl Chlorides 838 20.5 Preparation of Carboxylic Acid Anhydrides 841 20.6 Reactions of Carboxylic Acid Anhydrides 842 20.7 Sources of Esters 845 20.8 Physical Properties of Esters 846 20.9 Reactions of Esters: A Review and a Preview 846 20.10 Acid-Catalyzed Ester Hydrolysis 848 20.11 Ester Hydrolysis in Base: Saponification 852 20.12 Reaction of Esters with Ammonia and Amines 857 20.13 Thioesters 858 20.14 Preparation of Amides 859 20.15 Lactams 861 20.16 Imides 862 20.17 Hydrolysis of Amides 862 20.18 Preparation of Nitriles 867 Condensation Polymers: Polyamides and Polyesters 868 20.19 Hydrolysis of Nitriles 870 20.20 Addition of Grignard Reagents to Nitriles 871 20.21 Spectroscopic Analysis of Carboxylic Acid Derivatives 872 20.22 SUMMARY 874 Problems 877 ESTER ENOLATES886 21.1 The Claisen Condensation 887 21.2 Intramolecular Claisen Condensation: The Dieckmann Reaction 890 21.3 Mixed Claisen Condensations 891 21.4 Acylation of Ketones with Esters 892 21.5 Ketone Synthesis via b-Keto Esters 893 21.6 The Acetoacetic Ester Synthesis 894 21.7 The Malonic Ester Synthesis 897 21.8 Barbiturates 900 21.9 Michael Additions of Stabilized Anions 901 21.10 a Deprotonation of Carbonyl Compounds by Lithium Dialkylamides 902 21.11 SUMMARY 905 Problems 908 AMINES913 22.1 Amine Nomenclature 913 22.2 Structure and Bonding 916 22.3 Physical Properties 918 22.4 Basicity of Amines 919 22.5 Tetraalkylammonium Salts as Phase-Transfer Catalysts 923 Amines as Natural Products 924 22.6 Reactions That Lead to Amines: A Review and a Preview 926 22.7 Preparation of Amines by Alkylation of Ammonia 928 22.8 The Gabriel Synthesis of Primary Alkylamines 929 22.9 Preparation of Amines by Reduction 931 22.10 Reductive Amination 934 22.11 Reactions of Amines: A Review and a Preview 935 22.12 Reaction of Amines with Alkyl Halides 937 22.13 The Hofmann Elimination 938 22.14 Electrophilic Aromatic Substitution in Arylamines 939 22.15 Nitrosation of Alkylamines 943 22.16 Nitrosation of Arylamines 945 22.17 Synthetic Transformations of Aryl Diazonium Salts 946 22.18 Azo Coupling 950 From Dyes to Sulfa Drugs 951 22.19 Spectroscopic Analysis of Amines 951 22.20 SUMMARY 955 Problems 962 ARYL HALIDES971 23.1 Bonding in Aryl Halides 971 23.2 Sources of Aryl Halides 972 23.3 Physical Properties of Aryl Halides 972 23.4 Reactions of Aryl Halides: A Review and a Preview 973 23.5 Nucleophilic Substitution in Nitro-Substituted Aryl Halides 975 23.6 The Addition-Elimination Mechanism of Nucleophilic Aromatic Substitution 977 23.7 Related Nucleophilic Aromatic Substitution Reactions 980 23.8 The Elimination-Addition Mechanism of Nucleophilic Aromatic Substitution: Benzyne 981 23.9 Diels-Alder Reactions of Benzyne 985 23.10 SUMMARY 986 Problems 988 PHENOLS993 24.1 Nomenclature 993 24.2 Structure and Bonding 994 24.3 Physical Properties 995 24.4 Acidity of Phenols 996 24.5 Substituent Effects on the Acidity of Phenols 998 24.6 Sources of Phenols 999 24.7 Naturally Occurring Phenols 1001 24.8 Reactions of Phenols: Electrophilic Aromatic Substitution 1002 24.9 Acylation of Phenols 1004 24.10 Carboxylation of Phenols: Aspirin and the Kolbe-Schmitt Reaction 1006 24.11 Preparation of Aryl Ethers 1008 Agent Orange and Dioxin 1009 24.12 Cleavage of Aryl Ethers by Hydrogen Halides 1010 24.13 Claisen Rearrangement of Allyl Aryl Ethers 1011 24.14 Oxidation of Phenols: Quinones 1012 24.15 Spectroscopic Analysis of Phenols 1014 24.16 SUMMARY 1016 Problems 1019 CARBOHYDRATES1026 25.1 Classification of Carbohydrates 1026 25.2 Fischer Projections and D-L Notation 1027 25.3 The Aldotetroses 1029 25.4 Aldopentoses and Aldohexoses 1030 25.5 A Mnemonic for Carbohydrate Configurations 1032 25.6 Cyclic Forms of Carbohydrates: Furanose Forms 1032 25.7 Cyclic Forms of Carbohydrates: Pyranose Forms 1036 25.8 Mutarotation 1040 25.9 Ketoses 1041 25.10 Deoxy Sugars 1042 25.11 Amino Sugars 1042 25.12 Branched-Chain Carbohydrates 1043 25.13 Glycosides 1043 25.14 Disaccharides 1046 25.15 Polysaccharides 1048 25.16 Cell-Surface Glycoproteins 1050 How Sweet It Is! 1051 25.17 Carbohydrate Structure Determination 1052 25.18 Reduction of Carbohydrates 1052 25.19 Oxidation of Carbohydrates 1053 25.20 Cyanohydrin Formation and Chain Extension 1055 25.21 Epimerization, Isomerization, and Retro-Aldol Cleavage 1056 25.22 Acylation and Alkylation of Hydroxyl Groups in Carbohydrates 1058 25.23 Periodic Acid Oxidation of Carbohydrates 1059 25.24 SUMMARY 1061 Problems 1065 LIPIDS1069 26.1 Acetyl Coenzyme A 1070 26.2 Fats, Oils, and Fatty Acids 1071 26.3 Fatty Acid Biosynthesis 1075 26.4 Phospholipids 1077 26.5 Waxes 1079 26.6 Prostaglandins 1080 Nonsteroidal Antiinflammatory Drugs (NSAIDs) and COX-2 Inhibitors 1083 26.7 Terpenes: The Isoprene Rule 1084 26.8 Isopentenyl Pyrophosphate: The Biological Isoprene Unit 1087 26.9 Carbon-Carbon Bond Formation in Terpene Biosynthesis 1087 26.10 The Pathway from Acetate to Isopentenyl Pyrophosphate 1091 26.11 Steroids: Cholesterol 1093 Good Cholesterol? Bad Cholesterol? What's the Difference? 1096 26.12 Vitamin D 1096 26.13 Bile Acids 1097 26.14 Corticosteroids 1098 26.15 Sex Hormones 1098 Anabolic Steroids 1099 26.16 Carotenoids 1100 26.17 SUMMARY 1101 Problems 1103 AMINO ACIDS, PEPTIDES, AND PROTEINS1109 27.1 Classification of Amino Acids 1110 27.2 Stereochemistry of Amino Acids 1115 27.3 Acid-Base Behavior of Amino Acids 1117 Electrophoresis 1120 27.4 Synthesis of Amino Acids 1121 27.5 Reactions of Amino Acids 1123 27.6 Some Biochemical Reactions of Amino Acids 1123 27.7 Peptides 1126 27.8 Introduction to Peptide Structure Determination 1129 27.9 Amino Acid Analysis 1130 27.10 Partial Hydrolysis of Peptides 1130 27.11 End GroupAnalysis 1131 27.12 Insulin 1131 27.13 The Edman Degradation and Automated Sequencing of Peptides 1133 27.14 The Strategy of Peptide Synthesis 1135 27.15 Amino Group Protection 1137 27.16 Carboxyl Group Protection 1138 27.17 Peptide Bond Formation 1139 27.18 Solid-Phase Peptide Synthesis: The Merrifield Method 1141 27.19 Secondary Structures of Peptides and Proteins 1143 27.20 Tertiary Structure of Peptides and Proteins 1145 27.21 Coenzymes 1147 27.22 Protein Quaternary Structure: Hemoglobin 1148 Oh NO! It's Inorganic! 1149 27.23 SUMMARY 1150 Problems 1152 NUCLEOSIDES, NUCLEOTIDES, AND NUCLEIC ACIDS1155 28.1 Pyrimidines and Purines 1155 28.2 Nucleosides 1158 28.3 Nucleotides 1160 28.4 Bioenergetics 1162 28.5 ATP and Bioenergetics 1162 28.6 Phosphodiesters, Oligonucleotides, and Polynucleotides 1164 28.7 Nucleic Acids 1165 28.8 Secondary Structure of DNA: The Double Helix 1166 "It Has Not Escaped Our Notice . . ." 1167 28.9 Tertiary Structure of DNA: Supercoils 1170 28.10 Replication of DNA 1172 28.11 Ribonucleic Acids 1172 RNAWorld 1177 28.12 Protein Biosynthesis 1178 28.13 AIDS 1179 28.14 DNA Sequencing 1180 28.15 The Human Genome Project 1182 28.16 DNA Profiling and the Polymerase Chain Reaction 1183 28.17 SUMMARY 1186 Problems 1189 GLOSSARY G-1 CREDITS C-1 INDEX I-1 LIST OF BOXED ESSAYS INTRODUCTION Where Did the Carbon Come From? CHAPTER 1 Electrostatic Potential Maps Learning By Modeling Curved Arrows CHAPTER 2 Methane and the Biosphere A Brief History of Systematic Organic Nomenclature Thermochemistry CHAPTER 3 Molecular Mechanics Applied to Alkanes and Cycloalkanes Enthalpy, Free Energy, and Equilibrium Constant CHAPTER 4 From Bond Energies to Heats of Reaction CHAPTER 5 Ethylene CHAPTER 6 Rules, Laws, Theories, and the Scientific Method Ethylene and Propene: The Most Important Industrial Organic Chemicals CHAPTER 7 Chiral Drugs Chirality of Disubstituted Cyclohexanes CHAPTER 8 An Enzyme-Catalyzed Nucleophilic Substitution of an Alkyl Halide CHAPTER 9 Natural and "Designed" Enediyne Antibiotics CHAPTER 10 Diene Polymers CHAPTER 11 Benzene, Dreams, and Creative Thinking Carbon Clusters, Fullerenes, and Nanotubes CHAPTER 13 Ring Currents: Aromatic and Antiaromatic Magnetic Resonance Imaging Spectra by the Thousands Gas Chromatography, GC/MS, and MS/MS CHAPTER 14 An Organometallic That Occurs Naturally: Coenzyme B12 CHAPTER 15 Economic and Environmental Factors in Organic Synthesis CHAPTER 16 Polyether Antibiotics CHAPTER 17 Imines in Biological Chemistry CHAPTER 18 The Haloform Reaction and the Biosynthesis of Trihalomethanes CHAPTER 19 Quantitative Relationships Involving Carboxylic Acids CHAPTER 20 Condensation Polymers: Polyamides and Polyesters CHAPTER 22 Amines as Natural Products From Dyes to Sulfa Drugs CHAPTER 24 Agent Orange and Dioxin CHAPTER 25 How Sweet It Is! CHAPTER 26 Nonsteroidal Antiinflammatory Drugs (NSAIDs) and COX-2 Inhibitors Good Cholesterol? Bad Cholesterol? What's the Difference? Anabolic Steroids CHAPTER 27 Electrophoresis Oh NO! It's Inorganic! CHAPTER 28 "It Has Not Escaped Our Notice . . ." RNA World
Library of Congress Subject Headings for this publication:
Chemistry, Organic.