xii 8.22 Organizing What We Know About the Reactions of Organic Compounds (Group I)372 ESSENTIAL CONCEPTS 373 SUMMARY OF REACTIONS 374 PROBLEMS 375 TUTORIAL Drawing Resonance Contributors 382 PART Substitution and Elimination Reactions 39o THREE 9 Substitution and Elimination Reactions of Alkyl Halides 391 The S Reaction actors Reactions ctions 410 PROBLEM.SOLVING STRATEGY 411 NAlkyl Halides That Defend ganst Predators Ikyl Halides 4 PROBLEM-SOLVING STRATEGY 42】 品om2 PROBLEM-SOLVING STRATEGY 425 设 kyl Halide with a Nucleophile/Base 429 9.13 Benzylic Halides,Halides,Halides.and Ary Halides 4 914 Solvent 9.15 9.16 Intermolecular Versus Intramolecular Reactions 444 TEGY 44 9.17 the Problem 446 ESSEN TIAL CONCEPTS 449 ·SUMMARY OF REACTIONS450·PROBLEMS45I eactioschos,hers,Epxides,Amines,and Sulfur-Containing Compounds 458 10.1 GENERAL CONNECTION:Grain Alcohol and Wood Alcohol 462 10.2 I Halides 46 10.3 10.Reactions:Dehydration PROBLEM-SOLVING STRATEGY 471 :Biological Dehydrations 473 GENERAL CONNECTION:Blood Alcohol Concentration 476 Antabuse 476
PART THREE Substitution and Elimination Reactions 390 9 Substitution and Elimination Reactions of Alkyl Halides 391 ENVIRONMENTAL CONNECTION: The Birth of the Environmental Movement 392 9.1 The SN2 Reaction 393 9.2 Factors That Affect SN2 Reactions 398 CHEMICAL CONNECTION: Why Are Living Organisms Composed of Carbon Instead of Silicon? 405 9.3 The SN1 Reaction 406 9.4 Factors That Affect SN1 Reactions 409 9.5 Competition Between SN2 and SN1 Reactions 410 PROBLEM-SOLVING STRATEGY 411 BIOLOGICAL CONNECTION: Naturally Occurring Alkyl Halides That Defend Against Predators 412 9.6 Elimination Reactions of Alkyl Halides 412 9.7 The E2 Reaction 413 9.8 The E1 Reaction 419 PROBLEM-SOLVING STRATEGY 421 9.9 Competition Between E2 and E1 Reactions 422 9.10 E2 and E1 Reactions are Stereoselective 423 PROBLEM-SOLVING STRATEGY 425 9.11 Elimination from Substituted Cyclohexanes 427 9.12 Predicting the Products of the Reaction of an Alkyl Halide with a Nucleophile/Base 429 9.13 Benzylic Halides, Allylic Halides, Vinylic Halides, and Aryl Halides 433 PROBLEM-SOLVING STRATEGY 434 PROBLEM-SOLVING STRATEGY 437 9.14 Solvent Effects 438 CHEMICAL CONNECTION: Solvation Effects 438 ENVIRONMENTAL CONNECTION: Environmental Adaptation 441 9.15 Substitution and Elimination Reactions in Synthesis 442 9.16 Intermolecular Versus Intramolecular Reactions 444 PROBLEM-SOLVING STRATEGY 446 9.17 DESIGNING A SYNTHESIS II: Approaching the Problem 446 ESSENTIAL CONCEPTS 449 ■ SUMMARY OF REACTIONS 450 ■ PROBLEMS 451 10 Reactions of Alcohols, Ethers, Epoxides, Amines, and Sulfur-Containing Compounds 458 10.1 Nucleophilic Substitution Reactions of Alcohols: Forming Alkyl Halides 459 CHEMICAL CONNECTION: The Lucas Test 461 GENERAL CONNECTION: Grain Alcohol and Wood Alcohol 462 10.2 Other Methods Used to Convert Alcohols into Alkyl Halides 463 10.3 Converting an Alcohol Into a Sulfonate Ester 465 MEDICAL CONNECTION: The Inability to Perform an SN2 Reaction Causes a Severe Clinical Disorder 467 10.4 Elimination Reactions of Alcohols: Dehydration 468 PROBLEM-SOLVING STRATEGY 471 BIOLOGICAL CONNECTION: Biological Dehydrations 473 10.5 Oxidation of Alcohols 474 GENERAL CONNECTION: Blood Alcohol Concentration 476 MEDICAL CONNECTION: Treating Alcoholism with Antabuse 476 MEDICAL CONNECTION: Methanol Poisoning 477 The two chapters in the previous edition on substitution and elimination reactions of alkenes have been combined into one chapter. The recent compelling evidence showing that secondary alkyl halides do not undergo SN1 solvolysis reactions has allowed this material to be greatly simplified, so now it fits nicely into one chapter. xii 8.20 Aromatic Heterocyclic Compounds 368 8.21 How Benzene Reacts 370 8.22 Organizing What We Know About the Reactions of Organic Compounds (Group I) 372 ESSENTIAL CONCEPTS 373 ■ SUMMARY OF REACTIONS 374 ■ PROBLEMS 375 TUTORIAL Drawing Resonance Contributors 382
10.6 Nucleophilic Substitution Reactions of Ethers 477 10.7 MEDICAL CONNECTION:Anesthetics 47 ide CHEMICAL CONNECTION: CHEMICAL CONNECTION:Crown Ethers Can be Used to Catalyze SN2 Reactions 485 10.8 ENVIRONMENTAL CONNECTION:Benzo[a]pyrene and Cancer 488 10.9 CONNECTIO N:Lead Compounds for the Development of Drugs 491 HISTORICAL CONNECTION:Mustard Gas-A Chemical Warfare Agent495 CHEMICAL CONNECTION:Eradicating Termites497 ESSENTIAL CONCEPTS 500 SUMMARY OF REACTIONS 501 PROBLEMS 503 11 Organometallic Compounds 508 Organolithium and Organomagnesium Compounds09 ansmetallation 51 11.4 Palladium-Catalyzed Coupling Reactions515 115 PROBLEM-SOLVING STRATEGY 521 ISTORICAL CONNECTION:Grubbs,Schrock,Suzuki,and Heck Receive the Nobel Prize 526 HISTORICAL CONNECTION:The Nobel Prize 526 ESSENTIAL CONCEPTS 527SUMMARY OF REACTIONS 527PROBLEMS 528 Radicals 532 12.1 122 HISTORICAL CONNECTION:Why Radicals No Lo Have to Be Called Free Radicals 536 123 1路 The Distribution of Products Depends on Probability and Reactivity 537 MasteringChemistry for Organic Chemistry Formation of Explosive Peroxides 542 The Addition of Radicals to an Alkene 543 Radical Addition Reactions 546 Thes For ad nal pr with Multistep Synthesis 550 s in Bi Systems 552 einated Co e and the Cancer NUTRITIONAL CONNECTION:Is Chocolate a Health Food?556 12.12 nRadical Systems:Drawing ESSENTIAL CONCEPTS 558SUMM MARY OF REACTIONS 559.PROBLEMS 559 TUTORIAL Drawing Curved Arrows in Radical Systems 563
10.6 Nucleophilic Substitution Reactions of Ethers 477 MEDICAL CONNECTION: Anesthetics 478 10.7 Nucleophilic Substitution Reactions of Epoxides 480 CHEMICAL CONNECTION: Crown Ethers—Another Example of Molecular Recognition 484 CHEMICAL CONNECTION: Crown Ethers Can be Used to Catalyze SN2 Reactions 485 10.8 Arene Oxides 485 ENVIRONMENTAL CONNECTION: Benzo[a]pyrene and Cancer 488 ENVIRONMENTAL CONNECTION: Chimney Sweeps and Cancer 489 10.9 Amines Do Not Undergo Substitution or Elimination Reactions 490 BIOLOGICAL CONNECTION: Alkaloids 491 PHARMACEUTICAL CONNECTION: Lead Compounds for the Development of Drugs 491 10.10 Quaternary Ammonium Hydroxides Undergo Elimination Reactions 492 10.11 Thiols, Sulfides, and Sulfonium Ions 494 HISTORICAL CONNECTION: Mustard Gas–A Chemical Warfare Agent 495 MEDICAL CONNECTION: Alkylating Agents as Cancer Drugs 496 10.12 Methylating Agents Used by Chemists versus Those Used by Cells 496 CHEMICAL CONNECTION: Eradicating Termites 497 MEDICAL CONNECTION: S-Adenosylmethionine: A Natural Antidepressant 498 10.13 Organizing What We Know About the Reactions of Organic Compounds (Group II) 499 ESSENTIAL CONCEPTS 500 ■ SUMMARY OF REACTIONS 501 ■ PROBLEMS 503 11 Organometallic Compounds 508 11.1 Organolithium and Organomagnesium Compounds 509 11.2 Transmetallation 511 11.3 Organocuprates 512 11.4 Palladium-Catalyzed Coupling Reactions 515 PROBLEM-SOLVING STRATEGY 521 11.5 Alkene Metathesis 522 HISTORICAL CONNECTION: Grubbs, Schrock, Suzuki, and Heck Receive the Nobel Prize 526 HISTORICAL CONNECTION: The Nobel Prize 526 ESSENTIAL CONCEPTS 527 ■ SUMMARY OF REACTIONS 527 ■ PROBLEMS 528 12 Radicals 532 12.1 Alkanes are Unreactive Compounds 532 GENERAL CONNECTION: Natural Gas and Petroleum 533 GENERAL CONNECTION: Fossil Fuels: A Problematic Energy Source 533 12.2 The Chlorination and Bromination of Alkanes 534 HISTORICAL CONNECTION: Why Radicals No Longer Have to Be Called Free Radicals 536 12.3 Radical Stability Depends on the Number of Alkyl Groups Attached to the Carbon with the Unpaired Electron 536 12.4 The Distribution of Products Depends on Probability and Reactivity 537 12.5 The Reactivity–Selectivity Principle 539 PROBLEM-SOLVING STRATEGY 541 12.6 Formation of Explosive Peroxides 542 12.7 The Addition of Radicals to an Alkene 543 12.8 The Stereochemistry of Radical Substitution and Radical Addition Reactions 546 12.9 Radical Substitution of Allylic and Benzylic Hydrogens 547 CHEMICAL CONNECTION: Cyclopropane 550 12.10 DESIGNING A SYNTHESIS III: More Practice with Multistep Synthesis 550 12.11 Radical Reactions in Biological Systems 552 NUTRITIONAL CONNECTION: Decaffeinated Coffee and the Cancer Scare 553 NUTRITIONAL CONNECTION: Food Preservatives 555 NUTRITIONAL CONNECTION: Is Chocolate a Health Food? 556 12.12 Radicals and Stratospheric Ozone 556 MEDICAL CONNECTION: Artificial Blood 558 ESSENTIAL CONCEPTS 558 ■ SUMMARY OF REACTIONS 559 ■ PROBLEMS 559 TUTORIAL Drawing Curved Arrows in Radical Systems 563 for Organic Chemistry MasteringChemistry tutorials guide you through the toughest topics in chemistry with self-paced tutorials that provide individualized coaching. These assignable, in-depth tutorials are designed to coach you with hints and feedback specific to your individual misconceptions. For additional practice on Drawing Curved Arrows in Radical Systems, go to MasteringChemistry where the following tutorials are available: • Curved Arrows in Radical Systems: Interpreting Curved Arrows • Curved Arrows in Radical Systems: Drawing Curved Arrows • Curved Arrows in Radical Systems: Drawing Resonance Contributors The discussion of palladiumcatalyzed coupling reactions has been expanded, and the cyclic catalytic mechanisms are shown. xiii
xiv 6 Identification of Organic Compounds s66 Mass Spectrometry:ntrared Spectroscopy:UV/Vispctroscopy567 132 Mass Spectrometry 569 13.3 ineleMCalculate the Molecula Forml PROBLEM-SOLVING STRATEGY 573 Can Reveal Molecular Formulas 575 The Fragmentation Patterns of Functional Groups 575 13.3 SENERAL CONNECTION MC rometry 583 Characteristic Infrared Absorption Bands 88 13.14 and Hydrogen Bonding 591 PROBLEM-SOLVING STRATEGY 593 nds 598 Some Vibrations are Infrared Inactive 599 GENERAL CONNECTION:Ultraviolet Light and Sunscreens 603 605 13.22 13.23 Some Uses of UV/Vis Spectroscopy 608 berries Blue and Strawberries Red?607 ESSENTIAL CONCEPTS 610PROBLEMS 611 14 NMR Spectroscopy 620 14.1 (-193)62 Fourier Transform NMR 623 PROBLEM-SOLVING STRATEGY 625 The Chemical Shift Tells How r the Signal Is from the Reference Signal 626 The Characteristic Values of Chemical shifts Each Signal Is Described by the More Examples of H NMR Spectra 639 Protons 644 14.14 Splitting Diagram s Explain the Multiplicity of a Signal 647 Enantiot ic and Diastere ogens 650 Dependence copy
PART FOUR Identification of Organic Compounds 566 13 Mass Spectrometry; Infrared Spectroscopy; UV/Vis Spectroscopy 567 13.1 Mass Spectrometry 569 13.2 The Mass Spectrum • Fragmentation 570 13.3 Using The m/z Value of the Molecular Ion to Calculate the Molecular Formula 572 PROBLEM-SOLVING STRATEGY 573 13.4 Isotopes in Mass Spectrometry 574 13.5 High-Resolution Mass Spectrometry Can Reveal Molecular Formulas 575 13.6 The Fragmentation Patterns of Functional Groups 575 13.7 Other Ionization Methods 583 13.8 Gas Chromatography–Mass Spectrometry 583 GENERAL CONNECTION: Mass Spectrometry in Forensics 583 13.9 Spectroscopy and the Electromagnetic Spectrum 583 13.10 Infrared Spectroscopy 585 13.11 Characteristic Infrared Absorption Bands 588 13.12 The Intensity of Absorption Bands 589 13.13 The Position of Absorption Bands 590 GENERAL CONNECTION: The Originator of Hooke’s Law 590 13.14 The Position and Shape of an Absorption Band is Affected by Electron Delocalization and Hydrogen Bonding 591 PROBLEM-SOLVING STRATEGY 593 13.15 C¬H Absorption Bands 595 13.16 The Absence of Absorption Bands 598 13.17 Some Vibrations are Infrared Inactive 599 13.18 How to Interpret an Infrared Spectrum 600 13.19 Ultraviolet and Visible Spectroscopy 602 GENERAL CONNECTION: Ultraviolet Light and Sunscreens 603 13.20 The Beer–Lambert Law 604 13.21 The Effect of Conjugation on lmax 605 13.22 The Visible Spectrum and Color 606 CHEMICAL CONNECTION: What Makes Blueberries Blue and Strawberries Red? 607 13.23 Some Uses of UV/Vis Spectroscopy 608 ESSENTIAL CONCEPTS 610 ■ PROBLEMS 611 14 NMR Spectroscopy 620 14.1 An Introduction to NMR Spectroscopy 620 HISTORICAL CONNECTION: Nikola Tesla (1856–1943) 622 14.2 Fourier Transform NMR 623 14.3 Shielding Causes Different Nuclei to Show Signals at Different Frequencies 623 14.4 The Number of Signals in an 1H NMR Spectrum 624 PROBLEM-SOLVING STRATEGY 625 14.5 The Chemical Shift Tells How Far the Signal Is from the Reference Signal 626 14.6 The Relative Positions of 1H NMR Signals 628 14.7 The Characteristic Values of Chemical Shifts 629 14.8 Diamagnetic Anisotropy 631 14.9 The Integration of NMR Signals Reveals the Relative Number of Protons Causing Each Signal 632 14.10 The Splitting of Signals Is Described by the N + 1 Rule 634 14.11 What Causes Splitting? 637 14.12 More Examples of 1H NMR Spectra 639 14.13 Coupling Constants Identify Coupled Protons 644 PROBLEM-SOLVING STRATEGY 646 14.14 Splitting Diagrams Explain the Multiplicity of a Signal 647 14.15 Enantiotopic and Diastereotopic Hydrogens 650 14.16 The Time Dependence of NMR Spectroscopy 652 Chapters 13 and 14 are modular, so they can be covered at any time. In addition to the more than 170 spectroscopy problems in Chapters 13 and 14, there are 60 additional spectroscopy problems in the Study Guide and Solutions Manual. xiv
14.17 Protons Bonded to Oxygen and Nitrogen 652 657 GENERAL CONNECTION:Structural Databases 667 ESSENTIAL CONCEPTS 668PROBLEMS 669 PART Carbonyl Compounds FIVE 685 actins f Caboylic Acids an abi Acid Derivatives 15.1 The Nomer ature o Carboxylic Acids and Carboxylic Acid Derivatives 688 152 chapter exclusively React 694 ROBLEM-SOLVING STRATEGY 696 The Relative Reactivi acotcch3nacatogicAeaDetains6w drolysis and Transesterification 702 PHARMACEUTICAL CONNECTION: NSAIDS.and COX-2 Inhibitors 707 15.i0ReacioioeCtolAcita,7o91o BLE 15.11 BIOLOGICAL CONNECTION:Daimatians:Do Not Fool with Mother Nature 711 15.12 113 DCAL CONNE TION:Pen inand Drue Resistanc 713 714 15.13 Hydroysis of Amides MEDICAL CONNECTION:Disso ing Sutures 1 an Imide:Way to Amine 1516 Acid vdrides 719 GENERAL CONNECTION:What Drug-Enforcement Dogs Are Really Detecting 721 es727 SSENTIAL CONCEPTS 72B·SUMMARY OF REACTIONS729·PROBLEMS73 16 Reactions of Aldehydes and Ketones.More Reactions of Carboxylic Acid Derivatives 739 16.1 The 740 Compound 742 How Aldenydes and Ketones Reac
14.17 Protons Bonded to Oxygen and Nitrogen 652 14.18 The Use of Deuterium in 1H NMR Spectroscopy 654 14.19 The Resolution of 1H NMR Spectra 655 14.20 13C NMR Spectroscopy 657 PROBLEM-SOLVING STRATEGY 660 14.21 Dept 13C NMR Spectra 662 14.22 Two-Dimensional NMR Spectroscopy 662 14.23 NMR Used in Medicine is Called Magnetic Resonance Imaging 665 14.24 X-Ray Crystallography 666 GENERAL CONNECTION: Structural Databases 667 ESSENTIAL CONCEPTS 668 ■ PROBLEMS 669 PART FIVE Carbonyl Compounds 685 15 Reactions of Carboxylic Acids and Carboxylic Acid Derivatives 686 15.1 The Nomenclature of Carboxylic Acids and Carboxylic Acid Derivatives 688 MEDICAL CONNECTION: Nature’s Sleeping Pill 691 15.2 The Structures of Carboxylic Acids and Carboxylic Acid Derivatives 692 15.3 The Physical Properties of Carbonyl Compounds 693 15.4 How Carboxylic Acids and Carboxylic Acid Derivatives React 694 PROBLEM-SOLVING STRATEGY 696 15.5 The Relative Reactivities of Carboxylic Acids and Carboxylic Acid Derivatives 696 15.6 Reactions of Acyl Chlorides 698 15.7 Reactions of Esters 701 15.8 Acid-Catalyzed Ester Hydrolysis and Transesterification 702 15.9 Hydroxide-Ion-Promoted Ester Hydrolysis 706 PHARMACEUTICAL CONNECTION: Aspirin, NSAIDs, and COX-2 Inhibitors 707 15.10 Reactions of Carboxylic Acids 709 PROBLEM-SOLVING STRATEGY 710 15.11 Reactions of Amides 711 BIOLOGICAL CONNECTION: Dalmatians: Do Not Fool with Mother Nature 711 15.12 Acid-Catalyzed Amide Hydrolysis and Alcoholysis 712 HISTORICAL CONNECTION: The Discovery of Penicillin 713 MEDICAL CONNECTION: Penicillin and Drug Resistance 713 PHARMACEUTICAL CONNECTION: Penicillins in Clinical Use 714 BIOLOGICAL CONNECTION: A Semisynthetic Penicillin 714 15.13 Hydroxide-Ion-Promoted Hydrolysis of Amides 715 INDUSTRIAL CONNECTION: Synthetic Polymers 715 MEDICAL CONNECTION: Dissolving Sutures 716 15.14 Hydrolysis of an Imide: a Way to Synthesize a Primary Amine 716 15.15 Nitriles 717 15.16 Acid Anhydrides 719 GENERAL CONNECTION: What Drug-Enforcement Dogs Are Really Detecting 721 15.17 Dicarboxylic Acids 721 15.18 How Chemists Activate Carboxylic Acids 723 15.19 How Cells Activate Carboxylic Acids 724 CHEMICAL CONNECTION: Nerve Impulses, Paralysis, and Insecticides 727 ESSENTIAL CONCEPTS 728 ■ SUMMARY OF REACTIONS 729 ■ PROBLEMS 731 16 Reactions of Aldehydes and Ketones • More Reactions of Carboxylic Acid Derivatives 739 16.1 The Nomenclature of Aldehydes and Ketones 740 GENERAL CONNECTION: Butanedione: An Unpleasant Compound 742 16.2 The Relative Reactivities of Carbonyl Compounds 743 16.3 How Aldehydes and Ketones React 744 The focus of the first chapter on carbonyl chemistry is all about how a tetrahedral intermediate partitions. If students understand this, then carbonyl chemistry becomes pretty straightforward. I found that the lipid materil that had been put into this chapter in the last edition detracted from the main message of the chapter. Therefore, the lipid material was removed and put into a new chapter exclusively about lipids. xv
xvi 16.4 PROBLEM-SOLVING STRATEGY 749 Reactions Chemoselective Reactions 759 Re es with Nitr gen Nucleophiles 16.9 PROBLEM-SOLVING STRATEGY 771 Protecting Groups 772 774 16.14 DESIGNINGSYNTHESISIV:Disconnections.Synthons,and Synthetic Equivalents77 781 EMICAL CONNE ION.B- s-Tra 16.17 Reactions in Biological Systems7 ESSENTIAL CONCEPTS 787 SUMMARY OF REACTIONS 788.PROBLEMS 791 1 Reactions at the o-Carbon 801 The Acidity of an a-Hydrogen 8oa PROBLEM-SOLVING STRATEGY 804 Ke-no Carbon of Carboxylic Acids the a-Carbo 、81 17.8 Alkylating and Acylating Via an Enamine ntermediate Alkylating the B-Carbon 815 17.12 oe en Con EM-SOLVINGSTRTE 830 17.17 COCan be Removed from a Carboxylic Acid that has a Carbonyl Group at the 3-Position831 Malonic Este rSynthesis:A Wa to Synthesize a Ca 米 ESSENTIAL CONCEPTS 843 SUMMARY OF REACTIONS 844 PROBLEMS 846 TUTORIAL Synthesis and Retrosynthetic Analysis 854
16.4 Reactions of Carbonyl Compounds with Carbon Nucleophiles 745 CHEMICAL CONNECTION: Enzyme-Catalyzed Carbonyl Additions 747 PROBLEM-SOLVING STRATEGY 749 16.5 Reactions of Carbonyl Compounds with Hydride Ion 752 16.6 More About Reduction Reactions 757 16.7 Chemoselective Reactions 759 16.8 Reactions of Aldehydes and Ketones with Nitrogen Nucleophiles 760 PHARMACEUTICAL CONNECTION: Serendipity in Drug Development 765 16.9 Reactions of Aldehydes and Ketones with Oxygen Nucleophiles 766 BIOLOGICAL CONNECTION: Preserving Biological Specimens 768 CHEMICAL CONNECTION: Carbohydrates 770 PROBLEM-SOLVING STRATEGY 771 16.10 Protecting Groups 772 16.11 Reactions of Aldehydes and Ketones with Sulfur Nucleophiles 774 16.12 Reactions of Aldehydes and Ketones with a Peroxyacid 774 16.13 The Wittig Reaction Forms an Alkene 776 CHEMICAL CONNECTION: b-Carotene 777 16.14 DESIGNING A SYNTHESIS IV: Disconnections, Synthons, and Synthetic Equivalents 779 CHEMICAL CONNECTION: Synthesizing Organic Compounds 781 PHARMACEUTICAL CONNECTION: Semisynthetic Drugs 781 16.15 Nucleophilic Addition to a,b-Unsaturated Aldehydes and Ketones 781 16.16 Nucleophilic Addition to a,b-Unsaturated Carboxylic Acid Derivatives 785 CHEMICAL CONNECTION: Enzyme-Catalyzed Cis-Trans Interconversion 785 16.17 Conjugate Addition Reactions in Biological Systems 786 MEDICAL CONNECTION: Cancer Chemotherapy 786 ESSENTIAL CONCEPTS 787 ■ SUMMARY OF REACTIONS 788 ■ PROBLEMS 791 17 Reactions at the A-Carbon 801 17.1 The Acidity of an a-Hydrogen 802 PROBLEM-SOLVING STRATEGY 804 17.2 Keto–Enol Tautomers 805 17.3 Keto–Enol Interconversion 806 17.4 Halogenation of the a-Carbon of Aldehydes and Ketones 807 17.5 Halogenation of the a-Carbon of Carboxylic Acids 809 17.6 Forming an Enolate Ion 810 17.7 Alkylating the a-Carbon 811 INDUSTRIAL CONNECTION: The Synthesis of Aspirin 813 PROBLEM-SOLVING STRATEGY 813 17.8 Alkylating and Acylating the a-Carbon Via an Enamine Intermediate 814 17.9 Alkylating the b-Carbon 815 17.10 An Aldol Addition Forms a b-Hydroxyaldehyde or a b-Hydroxyketone 817 17.11 The Dehydration of Aldol Addition Products Forms a,b-Unsaturated Aldehydes and Ketones 819 17.12 A Crossed Aldol Addition 821 MEDICAL CONNECTION: Breast Cancer and Aromatase Inhibitors 823 17.13 A Claisen Condensation Forms a b-Keto Ester 824 17.14 Other Crossed Condensations 827 17.15 Intramolecular Condensations and Intramolecular Aldol Additions 827 17.16 The Robinson Annulation 830 PROBLEM-SOLVING STRATEGY 830 17.17 CO2 Can be Removed from a Carboxylic Acid that has a Carbonyl Group at the 3-Position 831 17.18 The Malonic Ester Synthesis: A Way to Synthesize a Carboxylic Acid 833 17.19 The Acetoacetic Ester Synthesis: A Way to Synthesize a Methyl Ketone 834 17.20 DESIGNING A SYNTHESIS V: Making New Carbon–Carbon Bonds 836 17.21 Reactions at the a-Carbon in Living Systems 838 17.22 Organizing What We Know About the Reactions of Organic Compounds (Group III) 841 ESSENTIAL CONCEPTS 843 ■ SUMMARY OF REACTIONS 844 ■ PROBLEMS 846 TUTORIAL Synthesis and Retrosynthetic Analysis 854 xvi This chapter was reorganized and rewritten for ease of understanding