An emphasis on problem solving and critical thinking, key to helping students successfully meet the science and technology needs of the future.Coverage of topics in green chemistry, nanotechnology, and biochemistry to introduce students to exciting and important frontiers of organic chemistry.

1 The Basics

BONDING AND MOLECULAR STRUCTURE 1

1.1 Life and the Chemistry of Carbon Compounds-We are Stardust 2

THE CHEMISTRY OF...Natural Products 3

1.2 Atomic Structure 3

1.3 Chemical Bonds:The Octet Rule 5

1.4 HOW TO Write Lewis Structures 7

1.5 Formal Charges and HOW TO Calculate Them 12

1.6 Isomers: Different Compounds that Have the Same Molecular Formula 14

1.7 HOW TO Write and Interpret Structural Formulas 15

1.8 Resonance 丁heory 22

1.9 Quantum Mechanics and Atomic Structure 27

1.10 Atomic Orbitals and Electron Configuration 28

1.11 Molecular Orbitals 30

1.12 The Structure of Methane and Ethane: sp3 Hybridization 32

THE CHEMISTRY OF... Calculated Molecular Models: Electron Density Surfaces 36

1.13 The Structure of Ethene (Ethylene): sp2 Hybridization 36

1.14 The Structure of Ethyne (Acetylene): sp Hybridizat ion 40

1.15 A Summary of Important Concepts That Come from Quantum ·Mechanics 43

1.16 HOW TO Predict Molecular Geometry:The Valence Shell Electron Pair Repulsion Model 44

1.17 Applicat ions of Basic Principles 47

[ WHY D THESE TOPICS MATTER? ] 48

2 Families of Carbon Compounds

FUNCTIONAL GROUPS, INTERMOLECULAR FORCES, AND INFRARED (IR) SPECTROSCOPY 55

2.1 Hydrocarbons : Representative Alkanes, Alkenes, Alkynes, and Aromatic Compounds 56

2.2 Polar Covalent Bonds 59

2.3 Polar and Nonpolar Molecules 61

2.4 Functional Groups 64

2.5 AlkyI Halides Or Haloalkanes 65

2.6 Alcohols and Phenols 67

2.7 Ethers 69

THE CHEMISTRY OF... Ethers as General Anesthetics 69

2.8 Amines 70

2.9 Aldehydes and Ketones 71

2.10 Carboxylic Acids, Esters, and Amides 73

2.11 Nitriles 75

2.12 Summary of lmportant Families of Organic Compounds 76

2.13 Physical Properties and Molecular Structure 77

THECHEMISTRY OF... Fluorocarbons and Teflon 82

2.14 Summary of Attractive Electric Forces 85

THE CHEMISTRY OF... Organic Templates Engineered to Mimic Bone Growth 86

2.15 lnfrared Spectroscopy: An Instrumental Method for Detecting Functional Groups 86

2.16 Interpreting IR Spectra 90

2.17 Applications of Basic Principles 97

[ VJHV DO T ESE TOPICS MATTER? ] 97

3 Acids and Bases

AN INTRODUCTION TO ORGANIC REACTIONS AND THEIR MECHANISMS 104

3.1 Acid-Base Reactions 105

3.2 HOW TO Use Curved Arrows in Illustrating Reactions 107

[ A MECHANISM F R THE REACTI ” ］ Reaction of Water with Hydrogen Chloride: The Use of Curved Arrows 107

3.3 Lewis Acids and Bases 109

3.4 Heterolysis of Bonds to Carbon: Carbocations and Carbanions 111

3.5 The Strength of Br0nsted-Lowry Acids and Bases: Ka and pK8 113

3.6 HOW TO Predict the Outcome of Acid-Base Reactions 118

3.7 Relationships Between Structure and Acidity 120

3.8 Energy Changes 123

3.9 The Relationship Between the Equilib「ium Constant and the Standard Free-Energy Change, t.G。125

3.10 Acidity: Carboxylic Acids versus Alcohols 126

3.11 The Effect of the Solvent on Ac idity 130

3.12 Organic Compounds as Bases 130

3.13 A Mechanism for an Organic Reaction 132

[ A MECHANISM F R T”E REACTI ” ］ Reaction of tert-Buty l Alcohol with Concentrated Aqueous HCI 132

3.14 Acids and Bases in Nonaqueous Solutions 133

3.15 Acid-Base Reactions and the Synthesis of Deute「ium- and T「itium-Labeled Compounds 134

3.16 Applications of Basic Principles 135

[ WHY DO THESE T PICS MATTER？】 136

4 Nomenclature and Confrmatins of Alkanes and Cycloalkanes 142

4.1 Introduction to Alkanes and Cycloalkanes 143

THE CHEMISTRY OF... Petroleum Refining 143

4.2 Shapes of Alkanes 144

4.3 HOW TO Name Alkanes, Alkyl Halides, and Alcohols: The IUPAC System 146

4.4 HOW TO Name Cycloalkanes 153

4.5 HOW TO Name Alkenes and Cycloalkenes 156

4.6 HOW TO Name Alkynes 158

4.7 Physical Properties of Alkanes and Cycloalkanes 159

THE CHEMISTRY OF ... Pheromones: Communication by Means of Chemicals 161

4.8 Sigma Bonds and Bond Rotation 162

4.9 Conformational Analysis of Butane 164

THE CHEMISTRY OF ... Muscle Action 166

4.10 The Relative Stabilities of Cyc loalkanes: Ring Strain 167

4.11 Conformations of Cyclohexane: The Chair and the Boat 168

THE CHEMISTRY ... Nanoscale Motors and Molecular Switches 170

4.12 Substituted Cyclohexanes : Axial and Equatorial Hydrogen Groups 171

4.13 Disubstituted Cycloalkanes: Cis-Trans Isomerism 175

4.14 Bicyclic and Polycyclic Alkanes 179

4.15 Chemical Reactions of Alkanes 180

4.16 Synthesis of Alkanes and Cycloalkanes 180

4.17 HOW TO Gain Structural Information from Molecular Formulas and the Index of Hydrogen Deficiency 182

4.18 Applications of Basic Principles 184

[ WHY DO THESE T PICS MATTER? ] 185

See SPECIAL TOPIC A:13C NMR Spectroscopy-A Practical Introduction in WileyPLUS

5 Stereochemistry

CHIRAL MOLECULES 191

5.1 Chirality and Stereochemistry 192

5.2 Isomerism: Constitutional Isomers and Stereoisomers 193

5.3 Enantiomers and Chiral Molecules 195

5.4 Molecules Having One Chirality Center are Chiral 196

5.5 More about the Biological Importance of Chirality 199

5.6 .HOW TO Test for Chirality: Planes of Symmetry 201

5.7 Naming Enantiomers: The R’S-System 202

5.8 Properties of Enantiomers: Optical Activity 206

5.9 The Origin of Optical Activity 211

5.10 The Synthesis of Chiral Molecules 213

5.11 Chiral Drugs 215

THE CHEMISTRY OF...Selective Binding of Drug Enantiomers to Left- and Right-Handed Coiled DNA 217

5.12 Molecules with More than One Chirality Center 217

5.13 Fischer Projection Formulas 223

5.14 Stereoisomerism of Cyclic Compounds 225

5.15 Relating Configurations through Reactions in which No Bonds to the Chirality Center Are Broken 227

5.16 Separation of Enantiomers: Resolution 231

5.17 Compounds with Chirality Centers Other than Carbon 232

5.18 Chiral Molecules That Do Not Possess a Chirality Center 232

[ WHY DO THESE TOPICS MATTER? ] 233

6 Ionic Reactionsel

NUCLEOPHILIC

SUBSTITUTION AND ELIMINATION REACTIONS OF A LKYL HALIDES 239

6.1 Alkyl Halides 240

6.2 Nucleophilic Substitution Reactions 241

6.3 Nucleophiles 243

6.4 Leaving Groups 245

6.5 Kinetics of a Nucleophilic Substitution Reaction: An SN2 Reaction 245

6.6 A Mechanism for the SN2 Reaction 246

[ A MECHANISM F R THE REACTION ] Mechanism for the SN2 Reaction 247

6.7 Transition State Theory: Free-Energy Diagrams 248

6.8 The Stereochemistry of SN2 Reactions 251

[ A MECHANISM F THE REACTION 】 The Stereochemistry of an SN2 Reaction 253

6.9 The Reaction of Tert-Butyl Chloride with Water:An SN1 Reaction 253

6.10 A Mechanism for the SN1 Reaction 254

[ A MECHANISM FOR THE REACTION ] Mechanism for the SN1 Reaction 255

6.11 Carbocations 256

6.12 The Stereochemistry of SN1 Reactions 258

[ A MECHANISM F R THE REACTION ] The Stereochemistry of an SN1 Reaction 259

6.13 Factors Affecting the Rates of SN1 and SN2 Reactions 261

6.14 Organic Synthesis: Functional Group Transformations Using SN2 Reactions 271

THE CHEMISTRY OF... Biological Methylation: A Biological Nucleophilic Substitution Reaction 273

6.15 Elimination Reactions of Alkyl Halides 275

6.16 The E2 Reaction 276

[ A MECHANISM FOR THE REACTION ] Mechanism for the E2 Reaction 277

6.17 The E1 Reaction 278

[ A MECHANISM FOR THE REACTION ] Mechanism for the E1 Reaction 279

6.18 HOW TO Determine Whether Substitution or Elimination Is Favored 280

6.19 Overall Summary 282

[ WYD THESE TOPICS MATTER? ] 283

7 Alkenes and Alkynes I

PROPERTIES AND SYNTHESIS. ELIMINATION EACTIONS OF ALK YL HALIDES 291

7.1 Introduction 292

7.2 The (E)-(Z) System for Designating Alkene Diastereomers 292

7.3 Relative Stabilities of Alkenes 293

7.4 Cycloalkenes 296

7.5 Synthesis of Alkenes via Elimination Reactions 296

7.6 Dehydrohalogenation of Alkyl Halides 297

[ A MECHANISM F R THE REACTION ] E2 Elimination

Where There Are Two Axial f3 Hydrogens 302

[ A MECHANISM FOR T”E REACTION ] E2 Elimination Where the Only Axial f3 Hydrogen Is from a Less Stable Conformer 302

7.7 Acid-Catalyzed Dehydration of Alcohols 303

[ A MECHANISM F THE REACTIN ] Acid-Catalyzed Dehydration of Secondary or Tertiary Alcohols: An E1 Reaction 307

[ A MECHANISM FOR THE R巨ACTION ] Dehydration of a Primary Alcohol: An E2 Reaction 308

7.8 Carbocation Stability and the Occurrence of Molecular Rearrar1gements 309

[ A MECHANISM FOR THE REACTION ]Formation of a Rearranged Alkene During Dehydration of a Primary Alcohol 312

7.9 The Acidity of Terminal Alkynes 313

7.10 Synthesis of Alkynes by Elimination Reactions 314

[ A MEC”ANISMFR THE REACTI ”]

Dehydrohalogenation of vic-Dibromides to Form Alkynes 315

7.11 Terminal Alkynes Can Be Converted to Nucleophiles for Carbon-Carbon Bond Formation 316 to Alkenes 359

7.12 Hydrogenation of Alkenes 318

THE CHEMISTRY OF... Hydrogenation in the Food industry 310

7.13 Hydrogenation:The Function of the Catalyst 320

7.14 Hydrogenation of Alkynes 321

[ A MECANISM FOR THE REACTION ] The Dissolving Metal Reduction of an Alkyne 322

7.15 An Introduction to Organic Synthesis 323

THE CHEMISTRY OF... From the Inorganic to the Organic 325

[ WHY DO THESE TOPICS MATTER? ] 327

8 Alkenes and Alkynes II

A DDITION R EAC丁IONS 337

8.1 Addition Reactions of Alkenes 338

8.2 Electrophilic Addition of Hydrogen Halides to Alkenes: Mechanism and Markovnikov’s Rule 340

[ A MECHANISM FOR THE REACTI ” ］ Addition of a Hydrogen Halide to an Alkene 341

[ A MECHANISM F R THE REACTI N ] Addition of HBr to 2-Methylpropene 343

8.3 Stereochemistry of the Ionic Addition to an Alkene 345

[ THE STEREOCHEMISTRY OF THE REACTION... ] Ionic Addition to an Alkene 345

8.4 Addition of Water to Alkenes: Acid-Catalyzed Hydration 346

[ A MECHANISM F R THE REACT，N ] Acid-Catalyzed Hydration of an Alkene 346

8.5 Alcohols from Alkenes through Oxymercuration- Demercuration: Markovnikov Addition 349

[ A MECHANISMFR THE REACTION ]

Oxymercuration 351

8.6 Alcoho ls from Alkenes through Hydroboration- Oxidation: Anti-Markovnikov Syn Hydration 352

8.7 Hydroboration:Synthesis of Alkylboranes 353

[ A MECHANISM FOR THE REACTION ]

Hydrboration 354

8.8 Oxidation and Hydrolysis of Alkylboranes 355

[ A MECHANISM FOR THE REACTION ] Oxidation of Trialkylboranes 356

8.9 Summary of Alkene Hydration Methods 358

8.10 Protonolysis of Alkylboranes 359

8.11 Electrophilic Addition of Bromine and Chlorine to Alenes 359

[ A MECHANISM FOR THE REACTION ] Addition of Bromine to an Alkene 361

THE CHEMISTRY OF... The Sea: A Treasury of Biologically Active Natural Products 362

8.12 Stereospecific Reactions 363

[THE STEREOCHEMISTRY OF THE REACTION...]

Addition of Bromine to cis- and trans-2-Butene 364

8.13 Halohydrin Formation 364

[ A MECHANISM FOR THE REACTION ] Halohydrin Formation from an Alkene 365

THE CHEMISTRY OF...Citrus-Flavored Soft Drinks 366

8.14 Divalent Carbon Compounds: Carbenes 366

8.15 Oxidation of Alkenes : Syn 1,2-Dihydroxylation 368

THE CHEMISTRY OF...Catalytic Asymmetric Dihydroxylation 370

8.16 Oxidative Cleavage of Alkenes 371

[ A MECHANISM FOR THE REACTION ］ Ozonolysis of an Alkene 373

8.17 Electrophilic Addition of Bromine and Chlorine to Alkynes 374

8.18 Addition of Hydrogen Halides to Alkynes 374

8.19 Oxidative Cleavage of Alkynes 375

8.20 HOW TO Plan a Synthesis: Some Approaches and Examples 376

[ WHY DO THESE TOPICS MATTER? ] 381

9 Nuclear Magnetic Res nance and Mass Spectrometry

TOOLS FOR S丁RUCTURE DETERMINA丁ION 391

9.1 Introduction 392

9.2 Nuclear Magnetic Resonance (NMR) Spectroscopy 392

9.3 HOW TO Interpret Proton NMR Spectra 398

9.4 Nuclear Spin:The Origin of the Signal 401

9.5 Detecting the Signal:Fourier Transform NMR Spectrometers 403

9.6 The Chemical Shift 405

9.7 Shielding and Deshielding of Protons 406

9.8 Chemical Shift Equivalent and Nonequivalent Protons 408

9.9 Signal Splitting: Spin-Spin Coupling 411

9.10 Proton NMR Spectra and Rate Processes 420

9.11 Carbon-13 NMR Spectroscopy 422

9.12 Two-Dimensional (20) NMR Techniques 428

THE CHEMISTRY F...Magnetic Resonance Imaging 1n Medicine 431

9.13 An Introduction to Mass Spectrometry 431

9.14 Formation of Ions: Electron Impact Ionization 432

9.15 Depicting the Molecular Ion 432

9.16 Fragmentation 433

9.17 Isotopes in Mass Spectra 440

9.18 GC/MS Analysis 443

9.19 Mass Spectrometry of Biomolecules 444

[ WHY DO THESE TOPICS MATTER? ] 444

10 Radical Reactions 457

10.1 Introduction: How Radicals Form and How They React 458

[ A MECHANISM FOR THE REACTI N ] Hydrogen Atom Abstraction 459

[ A MECHANISM FOR THE REACTION ] Radical Addition to a π Bond 459

THE CHEMISTRY OF Acne Medications 459

10.2 Homolytic Bond Dissociation Energies (DH0) 460

10.3 Reactions of Alkanes with Halogens 463

10.4 Chlorination of Methane: Mechanism of Reaction 465

[ A MECHAN.ISM FOR THE REACTION ] Radical Chlorination of Methane 465

10.5 Halogenation of Higher Alkanes 468

[ A MECHAN SM FOR THE REACTION ] Radical Halogenation of Ethane 468

10.6 The Geometry of Alkyl Radicals 471

10.7 Reactions That Generate Tetrahedral Chirality Centers 471

[ A MECHANISM F R THE REACTION ] The

Stereochemistry of Chlorination at C2 of Pentane 472

{ A MECHANISM F R THE REACT！”] The Stereochernistry of Chlorination at c3 of (S)-2-Chloropentane 473

10.8 A.llylic Substitution and A.llylic Radicals 475

10.9 Benzylic Substitution and Benzylic Radicals 478

10.10 Radical Addition to Alkenes: The Anti-Markovnikov Addition of Hydrogen Bromide 481

[ A MECHANISM FOR THE REACTION ] Anti-Markovnikov Addition of HBr 481

10.11 Radical Polymerization of Alkenes: Chain-Growth Polymers 483

[ A MECHANISM FOR THE REACTION ] Radical Polymerization of Ethene (Ethylene) 484

10.12 Other Important Radical Reactions 487

THE CHEMISTRY OF...Antiox idants 489

THE CHEMISTRY OF...Ozone Depletion and Chlorofluorocarbons (CFCs) 490

[ WHY DO THESE TOPICS MATTER? ] 491

See SPECIAL TOPIC B: Chain-Growth Polymers in WileyPLUS

11 AlcohoIs and Ethers

SYNT HESIS AND REACTIONS 498

11.1 Structure and Nomenclature 499

11.2 Physical Proper飞ies of Alcohols and Ethers 501

11.3 Important Alcohols and Ethers 503

THE CHEMISTRY F... Ethanol as a Biofuel 504

THE CHEMISTRY F... Choleste ol and Heart Disease 505

11.4 Synthesis of Alcohols from Alkenes 505

11.5 Reactions of Alcohols 507

11.6 Alcohols as Acids 509

11.7 Conversion of Alcohols into Alkyl Halides 510

11.8 Alkyl Halides from the Reaction of Alcohols with Hydrogen Halides 510

11.9 Alkyl Halides from the Reaction of Alcohols with PBr3 or SOCl2 513

11.10 Tosylates, Mesylates, and Triflates: Leaving Group Derivatives of Alcohols 514

[ A MECHAN SM FOR THE REACTION ] Conversion of an Alcohol into a Mesylate (an Alkyl Methanesulfonate) 516

11.11 Synthesis of Ethers 517

[ A MECHANISM FOR THE REACTION ] Intermolecular Dehydration of Alcohols to Form an Ether 517

[ A MEC”A NISM FOR THE REACTION ] The Williamson Ether Synthesis 518

11.12 Reactions of Ethers 522

[ A MECANISM FOR T E REACTION J Ether Cleavage by Strong Acids 522

11.13 Epoxides 523

[ A MECHANISM F R THE REACTI ” ］ Alkene Epoxidation 524

THE CHEM STRY OF...The Sharpless Asymmetric Epoxidation 524

11.14 Reactions of Epoxides 525

[ A MECHANISM FOR THE REACT，” ］ Acid-Catalyzed Ring Opening of an Epoxide 525

[ A MECHAN’SM F R T”E REACTION ] Base-Catalyzed Ring Opening of an Epoxide 526

11.15 Anti 1,2-Dihydroxylation of Alkenes via Epoxides 528

THE CHEMISTRY OF... Environmentally Friendly Alkene Oxidation Methods 530

11.16 Crown Ethers 531

THE CHEMISTRY OF...Transport Antibiotics and Crown Ethers 532

11.17 Summary of Reactions of Alkenes, Alcohols, and Ethers 532

[ WY D THESE T PICS MATTER? ] 534

12 Alcohols from Carbonyl Compounds

OXIDATION- EDUCTION AND ORGANOMETALLIC COMPOUNDS 542

12.1 Structure of the Carbonyl Group 543

12.2 Oxidation-Reduction Reactions in Organic Chemistry 544

12.3 Alcohols by Reduction of Carbonyl Compounds 546

[ A MECHANISM F R THE REACTION ] Reduction of Aldehydes and Ketones by Hydride Transfer 548

TEC EMISTRY OF... Alcohol Dehydrogenase-A Biochemical Hydride Reagent 548

THE CHEMISTRY F... Stereoselective Reductions of Carbonyl Groups 550

12.4 Oxidation of Alcohols 551

[ A MECHANISM F R THE REACTI N ] The Swem Oxidation 552

[ A MECHANISM F THE REACTI N ] Chromic Acid Oxidation 554

12.5 Organometallic Compounds 556

12.6 Prepatatio of Organolithium and Organomagnesium Compounds 557

12.7 Reactions of Organolithium and Organomagnesium Compounds 558

[ A MECHANISM FOR THE REACTION ］ The Grignard Reaction 561

12.8 Alcohols from Grignard Reagents 561

12.9 Protecting Groups 570

[ WHY DO THESE TOPICS MATTER? ] 571

See First Review Problem Set in WileyPLUS

13 Conjugated Unsaturated Systems 581

13.1 Introduction 582

13.2 The Stability of the Allyl Radical 582

13.3 The Allyl Cation 586

13.4 Resonance Theory Revisited 587

13.5 Alkadienes and Polyunsaturated Hydrocarbons 591

13.6 1,3-Butadiene: Electron Delocalization 592

13.7 The Stability of Conjugated Dienes 595

13.8 Ultraviolet-Visible Spectroscopy 596

13.9 Electrophilic Attack on c njugated Dienes: A1,4-Addition 604

13.10 The Diels-Alder Reaction: A 1,4-Cycloaddition Reaction of Dienes 608

THE CHEMISTRY OF... Molecules with the Nobel Prize in Their Synthetic Lineage 617

[ WHY DO THESE TOPICS MATTER? ] 617

14 Aromatic Compounds 626

14.1 The Discovery of Benzene 627

14.2 Nomenclature of Benzene Derivatives 628

14.3 Reactions of Benzene 630

14.4 The Kekule Structure for Benzene 631

14.5 The Thermodynamic Stability of Benzene 632

14.6 Modern Theories of the Structure of Benzene 634

14.7 Huckel's Rule:The 4n ＋ 2 τ Electron Rule 637

14.8 Other Aromatic Compounds 645

THE CHEMISTRY OF...Nanotubes 648

14.9 Heterocyclic Aromatic Compounds 648

14.10 Aromatic Compounds in Biochemistry 650

14.11 Spectroscopy of Aromatic Compounds 652

THE CHEMISTRY OF...Sunscreens (Catching the Sun’s Rays and What Happens to Them) 656

15 Reactions of Aromatic Compounds 669

15.1 Electrophilic Aromatic Substitution Reactions 670

15.2 A General Mechanism for Electrophilic Aromatic Substitution 671

15.3 Halogenation of Benzene 673

[ A MEC ANISM FOR THE REACTION ] Electrophilic Aromatic Bromination 673

15.4 Nitration of Benzene 674

[ A MECHANISM FOR THE REACTION ]Nitration of Benzene 675

15.5 Sulfonation of Benzene 675

[ A MECHA NISM FOR THE REACTION ] Sulfonation of Benzene 676

15.6 Friedel-Crafts Alkylation 676

[ A MECHANISM FOR THE REACTION ］ Friedel-Crafts Alkylation 677

15.7 Friedel-Crafts Acylation 678

[ A MECHANISM FOR THE REACTION ] Friedel-Crafts Acylation 680

15.8 Limitations of Friedel-Crafts Reactions 680

15.9 Synthetic Applications of Friedel-Crafts Acylations:The Clemmensen and Wolff-Kishner Reduction 83

15.10 Substituents Can Affect Both the Reactivity of the Ring and the Orientation of the Incoming Group 685

15.11 How Substituents Affect Electrophilic Aromatic Substitution: A Closer Look 690

15.12 Reactions of the Side Chain of Alkylbenzenes 699

THE CHEMISTRY OF... Industrial Styrene Synthesis 701

[ A MECHANISM FOR THE REACTION ] Benzylic Halogenation 701

15.13 Alkenylbenzenes 702

15.14 Synthetic Applications 704

15.15 Allylic and Benzylic Halides in Nucleophilic Substitution Reactions 708

15.16 Reduction of Aromatic Compounds 710

[ A MECHANISM FOR THE REACTION ] Birch Reduction 710

[ WHY DO THESE TOPICS MATTER? ] 711

16 Aldehydes and Ketones

NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP 720

16.1 Introduction 721

16.2 Nomenclature of Aldehydes and Ketones 721

16.3 Physical Properties 723

THE CHEMISTRY OF... Aldehydes and Ketones in Perfumes 724

16.4 Synthesis of Aldehydes 724

[ A MECHANISM FOR THE REACTION ] Reduction of an

Acyl Chloride to an Aldehyde 727

[ A MECHANISM FOR THE REACTION ] Reduction of an Ester to an Aldehyde 728

[ A MECHANISM FOR THE REACTION ] Reduction of a Nitrile to an Aldehyde 728

16.5 Synthesis of Ketones 729

16.6 Nucleophilic Addition to the Carbon-Oxygen Double Bond 732

[ A MECHANISM FOR THE REACTION ] Addition of a Strong Nucleophile to an Aldehyde or Ketone 733

[ A MECHANISM FOR THE REACTION ] Acid-Catalyzed Nucleophilic Addition to an Aldehyde or Ketone 733

16.7 The Addition of Alcohols: Hemiacetals and Acetals 735

[ A MECHANISM FOR THE REACTION ] Hemiacetal Formation 735

[ A MECHANISM FOR THE REACTION ] Acid-Catalyzed Hemiacetal Formation 736

[ A MECHANISM FOR THE REACTION ] Base-Catalyzed Hemiacetal Formation 736

[ A MECHANISM FOR THE REACTION ] Hydrate Formation 737

[ A MECHANISM FOR THE REACTION ] Acid-Catalyzed Acetal Formation 738

16.8 The Addition of Primary and Secondary Amines 741

[ A MECHANISM FOR THE REACTION ] Imine Formation 742

[ A MECHANISM FOR THE REACTION ] The Wolff-Kishner Reduction 743

THE CHEMISTRY OF...A Very Versatile Vitamin, Pyridoxine (Vitamin B6) 744

[ A MECHANISM FOR THE REACTION ] Enamine Formation 745

16.9 The Addition of Hydrogen Cyanide: Cyanohydrins 746

[ A MECHANISM FOR THE REACTION ] Cyanohydrin Formation 746

16.10 The Addition of YIides: The Wittig Reaction 747

[ A MECHANISM FOR THE REACTION ] The Wittig Reaction 749

16.11 Oxidation of Aldehydes 751

16.12 The Baeyer-Villiger Oxidation 751

[ A MECHANISM FOR THE REACTION ] The Baeyer-Villiger Oxidation 752

16.13 Chemical Analyses for Aldehydes and Ketones 753

16.14 Spectroscopic Prope「ties of Aldehydes and Ketones 753

16.15 Summa「y of Aldehyde and Ketone Addition Reactions 756

[ WHY DO THESE TOPICS MATTER? ] 757

17 Carboxylic Acids and Their Derivatives

NUCLEOPHILIC ADDITION-ELIMINATION AT THE ACYL CARBON 771

17.1 Introduction 772

17.2 Nomenclature and Physical Properties 772

17.3 Preparation of Carboxylic Acids 781

17.4 Acyl Substitution: Nucleophilic Addition-Elimination at the Acyl Carbon 784

[ A MECHANISM FOR THE REACTION ] Acyl Substitution by Nucleophilic Addition-Elimination 784

17.5 Acyl Chlorides 786

[ A MECHANISM FOR THE REACTION ] Synthesis of Acyl Chlorides Using Thionyl Chloride 787

17.6 Carboxylic Acid Anhydrides 788

17.7 Esters 789

[ A MECHANISM FOR THE REACTION ] Acid-Catalyzed Esterification 790

[ A MECHANISM FOR THE REACTION ] Base-Promoted Hydrolysis of an Ester 793

17.8 Amides 796

[ A MECHANISM FOR THE REACTION ] DCC-Promnoted Amide Synthesis 798

[ A MECHANISM FOR THE REACTION ] Acidic Hydrolysis of an Amide 799

[ A MECHANISM FOR THE REACTION ] Basic Hydrolysis of an Amide 799

[ A MECHANISM FOR THE REACTION ] Acidic Hydrolysis of a Nitrile 801

[ A MECHANISM FOR THE REACTION ] Basic Hydrolysis of a Nitrile 801

17.9 Derivatives of Carbonic Acid 802

17.10 Decarboxylation of Carboxylic Acids 805

17.11 Chemical Tests for Acyl Compounds 807

17.12 Polyesters and Polyamides: Step-Growth Polymers 807

17.13 Summary of the Reactions of Carboxylic Acids and Their Derivatives 809

[ WHY DO THESE TOPICS MATTER? ] 812

18 Reactions at the α Carbon of Carbonyl Compounds

ENOLS AND ENOLATES 821

18.1 The Acidity of the a Hydrogens of Carbonyl Compounds: Enolate Anions 822

18.2 Keto and Enol Tautomers 823

18.3 Reactions via Enols and Enolates 825

[ A MECHANISM FOR THE REACTION ] Base-Catalyzed Enolization 825

[ A MECHANISM FOR THE REACTION ] Acid-Catalyzed Enolization 826

[ A MECHANISM FOR THE REACTION ] Base-Promoted Halogenation of Aldehydes and Ketones 827

[ A MECHANISM FOR THE REACTION ] Acid-Catalyzed Halogenation of Aldehydes and Ketones 828

[ A MECHANISM FOR THE REACTION ] The Haloform Reaction 829

THE CHEMISTRY OF... Chloroform in Drinking Water 829

18.4 Lithium Enolates 831

18.5 Enolates of β Dicarbonyl Compounds 834

18.6 Synthesis of Methyl Ketones:The Acetoacetic Ester Synthesis 835

18.7 Synthesis of Subst ituted Acetic Acids: The Malonic Ester Synthesis 840

[ A MECHANISM FOR THE REACTION ] The Malonic Ester Synthesis of Substituted Acetic Acids 840

18.8 Further Reactions of Active Hydrogen Compounds 844

18.9 Synthesis of Enamines:Stork Enamine Reactions 844

18.10 Summary of Enolate Chemistry 847

[ WHY DO TOPICS MATTER? ] 849

See SPECIAL TOPIC C:Step-Growth Polymers in WileyPLUS

19 Condensation and Conjugate Addition Reactions of Carbonyl Compounds

MORE CHEMIS丁RY OF ENOLATES 858

19.1 Introduction 859

19.2 The Claisen Condensation:A Synthesis of β Keto Esters 859

[ A MECHANISM FOR THE REACTION ] The Claisen Condensation 860

[ A MECHANISM FOR THE REACTION ] The Dieckmann Condensation 862

19.3 β Dicarbonyl Compounds by Acylation of Ketone Enolates 864

19.4 Aldol Reactions:Addition of Enolates and Enols to Aldehydes and Ketones 865

[ A MECHANISM FOR THE REACTION ] The Aldol Addition 866

[ A MECHANISM FOR THE REACTION ] Dehydration of the Aldol Addition Product 867

[ A MECHANISM FOR THE REACTION ] The Acid­Catalyzed A ldo/ React on 867

[ A MECHANISM F R THE REACTI ” J

19.6 Cyclizations via Aldol Condensations 876

[ A MECHANISM FOR THE REACTION ] The Aldol Cychlization 877

19.7 Additions to a β Unsaturated Aldehydes and Ketones 877

[ A MECHANISM FOR THE REACTION ] The Conjugate Addition of HCN 879

[ A MECHANISM FOR THE REACTION ] The Conjugate Addit ion of an Amine 879

[ A MECHANISM FOR THE REACTION ] The Michael Addition 880

THE CHEMISTRY OF...Conjugate Additions to Activate Drugs 881

19.8 The Mannich Reaction 882

[ A MECHANISM FOR THE REACTION ] Reaction 882

THE CHEMISTRY OF... A Suicide Enzyme Substrate 883

19.9 Summary of Important Reactions 884

[ WHY DO THESE TOPICS MATTER? ] 885

See SPECIAL TOPIC D: Thiols, Sulfur Ylides, and Disulfides in WileyPLUS

See SPECIAL TOPIC E: Thiol Esters and Lipid

20 Amines 897

20.1 Nomenclature 898

20.2 Physical Properties and Structure of Amines 899

20.3 Basicity of Amines: Amine Salts 901

THE CHEMISTRY OF... Biologically Important Amines 906

20.4 Preparation of Amines 908

[ A MECHANISM FOR THE REACTION ] A lkylatron of NH3 909

[ A MECHANISM FOR THE REACTION ] Reductive Amination 912

[ A MECHANISM FOR THE REACTION ] The Hofmann Rearrangement 915

20.5 Reactions of Amines 917

20.6 Reactions of Amines with Nitrous Ac id 918

[ A MECHANISM FOR THE REACTION ]Diazotization 919

THE CHEMISTRY OF... N-Nitrosoamines 919

20.7 Replacement Reactions of Arenediazonium Salts 920

20.8 Coupling Reactions of Arenediazonium Salts 924

20.9 Reactions of Amines with Sulfonyl Chlorides 926

THE CHEMISTRY OF... Essential Nutrients and Antimetabolites 927

20.10 Synthesis of Sulfa Drugs 928

20.11 Analysis of Amines 929

20.12 Eliminations Involving Ammonium Compounds 931

20.13 Summary of Preparations and Reactions of Amines 932

[ WHY DO THESE TOPICS MATTER? ] 934

See SPECIAι TOPIC F:Alkaloids in WileyPLUS

21 Phenols and Aryl Halides

NUCLEOPHILIC AROMATIC SUBSTITUTION 944

21.1 Structure and Nomenclature of Phenols 945

21.2 Naturally Occurring Phenols 946

21.3 Physical Properties of Phenols 947

21.4 Synthesis of Phenols 947

21.5 Reactions of Phenols as Acids 949

21.6 Other Reactions of the 0-H Group of Phenols 952

21.7 Cleavage of Alkyl Aryl Ethers 952

21.8 Reactions of the Benzene Ring of Phenols 953

THE CHEMISTRY OF... Polyketide Anticancer Antibiotic Biosynthesis 954

21.9 The Claisen Rear「angement 956

21.10 Quinones 957

THE CHEMISTRY OF...The Bombardier Beetle’s Noxious Spray 958

21.11 Aryl Halides and Nucleophilic Aromatic Substitution 959

[ A MECHANISM FOR THE REACTION ] The SNAr Mechanism 960

THE CHEMISTRY OF... Bacterial Dehalogenation of a PCB Derivative 961

[ A MECHANISM FOR THE REACTION ] The Benzyne Elimination-Addition Mechanism 962

21.12 Spectroscopic Analysis of Phenols and Aryl Halides 966

THE CHEMISTRY OF...Aryl Halides: Their Uses and Environmental Concerns 967

[ WHY DO THESE T PICS MATTER? ] 969

See Second Review Problem Set in WileyPLUS

SPECIAL T PIC G:Carbon-Carbon Bond-Forming and Other Reactions of Transition Metal Organometallic Compounds ONLINE

See SPECIAL TOPIC H: Electrocyclic and Cycloaddition Reactions in WileyPLUS

22 Carbohydrates 979

22.1 Introduction 980

22.2 Monosaccharides 982

22.3 Mutarotation 987

22.4 Glycoside Formation 988

[ A MECHANISM FOR THE REACTION ] Formation of a Glycoside 988

[ A MECHANISM FOR THE REACTION ] Hydrolysis of a Glycoside 989

22.5 Other Reactions of Monosacchar ides 990

22.6 Oxidation Reactions of Monosaccharides 994

22.7 Reduction of M nosaccharides: Alditols 999

22.8 Reactions of Monosaccharides with Phenylhydrazine:Osazones 999

[ A MECHANISM FOR THE REACTION ] Phenylosazone Formation 1000

22.9 Synthesis and Degradation of Monosaccharides 1000

22.10 The o Family of Aldoses 1002

22.11 Fischer's Proof of the configuration of o-(+)-Glucose 1003

22.12 Disaccharides 1005

THE CHEMISTRY OF...Artificial Sweeteners (How Sweet It Is) 1008

22.13 Polysaccharides 1009

22.14 Other Biologically Important Sugars 1013

22.15 Sugars That Contain Nitrogen 1014

22.16 Glycolipids and Glycoproteins of the Cell Surface: Cell Recognition and the Immune System 1016

THE CHEMISTRY OF... Patroling Leukocytes and Sialyl Lewis" Acids 1018

22.17 Carbohydrate Antibiotics 1018

22.18 Summary of Reactions of Carbohydrates 1019

[ WY DO THESE TOPICS MATTER? ] 1020

23 Lipids 1021

23.1 Introduction 1028

23.2 Fatty Acids and Triacylglycerols 1028

THE CHEMISTRY OF... Olestra and Other Fat Substitutes 1032

THE CHEMISTRY OF... Self-Assembled Monolayers­ Lipids in Materials Science and Bioengineering 1036

23.3 Terpenes and Terpenoids 1037

23.4 Steroids 1040

THE CHEMISTRY OF... The Enzyme Aromatase 1046

23.5 Prostaglandins 1049

23.6 Phospholipids and Cell Membranes 1050

THE CHEMISTRY OF... STEALTH® Liposomes for Drug Delivery 1053

23.7 Waxes 1054

[ WHY DO THESE TOPICS MATTER? ] 1054

24 Amino Acids and Proteins 1060

24.1 Introduction 1061

24.2 Amino Acids 1062

24.3 Synthesis of a-Amino Acids 1068

[ A MECHANISM FOR THE REACTION ] Formation of an a-Aminonitrile during the Strecker Synthesis 1069

24.4 Polypeptides and Proteins 1070

24.5 Primary Structure of Polypeptides and Proteins 1073

24.6 Examples of Polypeptide and Protein Primary Structure 1077

THE CHEMISTRY OF... Sickle-Cell Anemia 1079

24.7 Polypeptide and Protein Synthesis 1080

24.8 Secondary, Tertiary, and Quaternary Structures of Proteins 1086

24.9 lntroduction to Enzymes 1090

24.10 Lysozyme: Mode of Action of an Enzyme 1092

THE CHEMISTRY OF... Carbonic Anhydrase: Shuttling the Protons 1094

24.11 Serine Proteases 1094

24.12 Hemoglobin: A Conjugated Protein 1096

THE CHEMISTRY OF... Some Catalytic Antibodies 1096

24.13 Purification and Analysis of Polypeptides and Proteins 1098

24.14 Proteomics 1100

[ WHY DO THESE TOPICS MATTER? ] 1102

25 Nucleic Acids and Protein Synthesis 1105

25.1 Introduction 1106

25.2 Nucleotides and Nucleosides 1107

25.3 Laboratory Synthesis of Nucleosides and Nucleotides 1110

25.4 Deoxyribonucleic Acid: DNA 1113 25.5 RNA and Protein Synthesis 1120

25.6 Determining the Base Sequence of DNA: The Chain-Terminating (Oideoxynucleotide) Method 1128

25.7 Laboratory Synthesis of Oligonucleotides 1131

25.8 The Polymerase Chain Reaction 1133

25.9 Sequencing of the Human Genome: An Instruction Book for the Molecules of Life 1135

[ WHY DO THESE T PICS MATTER? ] 1136

ANSWERS TO SELECTED PROBLEMS A-1

GLOSSARY GL-1INDEX I-1

SCOTT A. SNYDER is Associate Professor of Chemisrry at Columbia Universiry. He grew up in the suburbs of Buffalo NY and was an undergraduate at Williams College, where he graduated summa cum laude in 1999, before pursuing his doccoral studies ar The Scripps Research lnsciruce under the rutelege of K. C. Nicolaou as an NSF, Pfizer, and Bristol-Myers-Squibb predocroraJ fellow. While there, he co-authored the graduate textbook Classics in Total Synthesis II with his doctoral mentor. Scott was then an NIH postdoctoral fellow in the laborarories of E.J. Corey at Harvard University before assuming his cur-rent posicion in 2006. His research inrerests lie in the arena f natural products total synthesis, especially in the realm of unique polyphenols and halogenared materials, and to date he has trained more than 60 srudencs at the high school, undergraduate, graduate, and postdoctoral levels and co-authored more than 40 research and review articles. Scott has received a number of awards and honors，including a Camille and Henry Dreyfus New Faculty Award, Amgen New Faculty and Young Investigator Awards, Eli Lilly New Faculty and Granree Awards, a Bristol-Myers Squibb Unrestricted Grant Award, an NSF CAREER Award, an Alfred P. Sloan Foundation Fellowship, a DuPont Young Professor Award, and an Arthur C. Cope Scholar Award from the American Chemical Society. He has also received recognition for his teaching through a Corrrell Schobr Award from the Research Corporarion for Science Advancement and a Columbia Presidential Teaching Award. He is a member of the international advisory board for The Chemicrtl Record and the edirorial board of Chimlity. He lives north of New York City with his wife Cathy where he enjoys gardening, cooking, and watching movies.

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