Organic Chemistry

Cover page......Page 1
Title Page......Page 9
Copyright Page......Page 10
Brief Contents......Page 11
Contents......Page 12
Preface......Page 25
Acknowledgments......Page 33
About the Authors......Page 36
To the Student......Page 37
1 The Basics Bonding and Molecular Structure......Page 39
1.2 Atomic Structure......Page 40
1.2B Valence Electrons......Page 42
1.3A Isomers: The Importance of Structural Formulas......Page 43
1.3B The Tetrahedral Shape of Methane......Page 44
1.4A Ionic Bonds......Page 45
1.4B Covalent Bonds and Lewis Structures......Page 46
1.5 How to Write Lewis Structures......Page 47
1.6 Exceptions to the Octet Rule......Page 49
1.7 Formal Charges and How to Calculate Them......Page 51
1.8 Resonance Theory......Page 53
1.8A How to Write Resonance Structures......Page 55
1.9 Quantum Mechanics and Atomic Structure......Page 58
1.10 Atomic Orbitals and Electron Configuration......Page 59
1.10A Electron Configurations......Page 60
1.11 Molecular Orbitals......Page 61
1.12 The Structure of Methane and Ethane: sp³ Hybridization......Page 63
1.12A The Structure of Methane......Page 64
1.12B The Structure of Ethane......Page 66
THE CHEMISTRY OF . . . Calculated Molecular Models: Electron Density Surfaces......Page 67
1.13 The Structure of Ethene (Ethylene): sp² Hybridization......Page 68
1.13A Restricted Rotation and the Double Bond......Page 70
1.13B Cis–Trans Isomerism......Page 71
1.14 The Structure of Ethyne (Acetylene): sp Hybridization......Page 72
1.15 A Summary of Important Concepts that Come from Quantum Mechanics......Page 74
1.16B Ammonia......Page 76
1.16D Boron Trifluoride......Page 77
1.16F Carbon Dioxide......Page 78
1.17A Dash Structural Formulas......Page 79
1.17B Condensed Structural Formulas......Page 80
1.17C Bond-Line Formulas......Page 81
1.17D Three-Dimensional Formulas......Page 83
1.18 Applications of Basic Principles......Page 84
2 Families of Carbon Compounds Functional Groups, Intermolecular Forces, and Infrared (IR) Spectroscopy......Page 91
2.1A Alkanes......Page 92
2.1C Alkynes......Page 93
2.1D Benzene: A Representative Aromatic Hydrocarbon......Page 94
2.2 Polar Covalent Bonds......Page 95
THE CHEMISTRY OF . . . Calculated Molecular Models: Maps of Electrostatic Potential......Page 97
2.3 Polar and Nonpolar Molecules......Page 98
2.4 Functional Groups......Page 100
2.4A Alkyl Groups and the Symbol R......Page 101
2.5 Alkyl Halides or Haloalkanes......Page 102
2.6 Alcohols......Page 103
THE CHEMISTRY OF . . . Ethers as General Anesthetics......Page 105
2.8 Amines......Page 106
2.9 Aldehydes and Ketones......Page 107
2.10A Carboxylic Acids......Page 108
2.10B Esters......Page 109
2.12 Summary of Important Families of Organic Compounds......Page 110
2.13 Physical Properties and Molecular Structure......Page 111
2.13A Ionic Compounds: Ion–Ion Forces......Page 112
2.13B Intermolecular Forces (van der Waals Forces)......Page 113
THE CHEMISTRY OF . . . Fluorocarbons and Teflon......Page 116
2.13D Solubilities......Page 117
2.13F Intermolecular Forces in Biochemistry......Page 119
THE CHEMISTRY OF . . . Organic Templates Engineered to Mimic Bone Growth......Page 120
2.15 Infrared Spectroscopy: An Instrumental Method for Detecting Functional Groups......Page 121
2.16A Infrared Spectra of Hydrocarbons......Page 125
2.16B IR Spectra of Some Functional Groups Containing Heteroatoms......Page 127
2.17 Applications of Basic Principles......Page 130
3 An Introduction to Organic Reactions and Their Mechanisms Acids and Bases......Page 136
3.1 Reactions and Their Mechanisms......Page 137
3.1A Homolysis and Heterolysis of Covalent Bonds......Page 138
3.2A Brønsted–Lowry Acids and Bases......Page 139
3.3 Lewis Acids and Bases......Page 140
3.3A Opposite Charges Attract......Page 141
3.4 Heterolysis of Bonds to Carbon: Carbocations and Carbanions......Page 142
THE CHEMISTRY OF . . . HOMOs and LUMOs in Reactions......Page 143
3.5 How to Use Curved Arrows in Illustrating Reactions......Page 144
3.6A The Acidity Constant, K[sub(a)]......Page 147
3.6B Acidity and pK[sub(a)]......Page 148
3.6C Predicting the Strength of Bases......Page 150
3.7 How to Predict the Outcome of Acid–Base Reactions......Page 151
3.7A Water Solubility as the Result of Salt Formation......Page 152
3.8 Relationships between Structure and Acidity......Page 153
3.8A The Effect of Hybridization......Page 155
3.8B Inductive Effects......Page 156
3.9 Energy Changes......Page 157
3.10 The Relationship between the Equilibrium Constant and the Standard Free-Energy Change, ΔG°......Page 158
3.11 The Acidity of Carboxylic Acids......Page 159
3.11A The Effect of Delocalization......Page 160
3.11B The Inductive Effect......Page 161
3.11D Inductive Effects of Other Groups......Page 162
3.12 The Effect of the Solvent on Acidity......Page 163
3.13 Organic Compounds as Bases......Page 164
3.14 A Mechanism for an Organic Reaction......Page 165
3.15 Acids and Bases in Nonaqueous Solutions......Page 166
3.16 Acid–Base Reactions and the Synthesis of Deuterium-and Tritium-Labeled Compounds......Page 168
3.17 Applications of Basic Principles......Page 169
4 Nomenclature and Conformations of Alkanes and Cycloalkanes......Page 175
4.1A Sources of Alkanes: Petroleum......Page 176
THE CHEMISTRY OF . . . Petroleum Refining......Page 177
4.2 Shapes of Alkanes......Page 178
4.3A Nomenclature of Unbranched Alkyl Groups......Page 180
4.3B Nomenclature of Branched-Chain Alkanes......Page 181
4.3C Nomenclature of Branched Alkyl Groups......Page 183
4.3E Nomenclature of Alkyl Halides......Page 185
4.3F Nomenclature of Alcohols......Page 186
4.4A Monocyclic Compounds......Page 187
4.4B Bicyclic Compounds......Page 188
4.5 Nomenclature of Alkenes and Cycloalkenes......Page 189
4.7 Physical Properties of Alkanes and Cycloalkanes......Page 192
THE CHEMISTRY OF . . . Pheromones: Communication by Means of Chemicals......Page 194
4.8A Newman Projections and How to Draw Them......Page 195
4.8B How to Do a Conformational Analysis......Page 196
4.9 Conformational Analysis of Butane......Page 198
4.9A Stereoisomers and Conformational Stereoisomers......Page 199
4.10A Cyclopropane......Page 200
4.11 Conformations of Cyclohexane: The Chair and the Boat......Page 201
4.12 Substituted Cyclohexanes: Axial and Equatorial Hydrogen Groups......Page 205
THE CHEMISTRY OF . . . Nanoscale Motors and Molecular Switches......Page 204
4.12B A Conformational Analysis of Methylcyclohexane......Page 206
4.12C 1,3-Diaxial Interactions of a tert-Butyl Group......Page 208
4.13A Cis–Trans Isomerism and Conformational Structures of Cyclohexanes......Page 209
4.14 Bicyclic and Polycyclic Alkanes......Page 213
THE CHEMISTRY OF . . . Elemental Carbon......Page 214
4.16A Hydrogenation of Alkenes and Alkynes......Page 215
4.17 How to Gain Structural Information from Molecular Formulas and the Index of Hydrogen Deficiency......Page 216
4.17A Compounds Containing Halogens, Oxygen, or Nitrogen......Page 218
4.18 Applications of Basic Pfinciples......Page 219
See SPECIAL TOPIC A: 13C NMR Spectroscopy – A Practical Introduction in Wiley PLUS......Page 223
5.1 Chirality and Stereochemistry......Page 224
5.1A The Biological Significance of Chirality......Page 225
5.2C Enantiomers and Diastereomers......Page 226
5.3 Enantiomers and Chiral Molecules......Page 228
5.4 A Single Chirality Center Causes a Molecule to Be Chiral......Page 229
THE CHEMISTRY OF . . . Life’s Molecular Handedness......Page 231
5.5 More about the Biological Importance of Chirality......Page 232
5.6 How to Test for Chirality: Planes of Symmetry......Page 233
5.7 Naming Enantiomers: The R,S-System......Page 234
5.7A How to Assign (R) and (S) Configurations......Page 235
5.8 Properties of Enantiomers: Optical Activity......Page 239
5.8A Plane-Polarized Light......Page 240
5.8B The Polarimeter......Page 241
5.8C Specific Rotation......Page 242
5.9 The Origin of Optical Activity......Page 243
5.9A Racemic Forms......Page 244
5.10A Racemic Forms......Page 245
5.10B Stereoselective Syntheses......Page 246
5.11 Chiral Drugs......Page 247
5.12 Molecules with More than One Chirality Center......Page 249
5.12A Meso Compounds......Page 251
5.12B How to Name Compounds with More than One Chirality Center......Page 252
5.13 Fischer Projection Formulas......Page 253
5.13A How to Draw and Use Fischer Projections......Page 254
5.14A Cyclohexane Derivatives......Page 255
5.15 Relating Configurations through Reactions in Which No Bonds to the Chirality Center Are Broken......Page 257
5.15A Relative and Absolute Configurations......Page 258
5.16B Current Methods for Resolution of Enantiomers......Page 261
5.18 Chiral Molecules that Do Not Possess a Chirality Center......Page 262
6 Ionic Reactions Nucleophilic Substitution and Elimination Reactions of Alky lHalides......Page 268
6.1 Organic Halides......Page 269
6.1A Physical Properties of Organic Halides......Page 270
6.2 Nucleophilic Substitution Reactions......Page 271
6.3 Nucleophiles......Page 272
6.5A How Do We Measure the Rate of This Reaction?......Page 275
6.6 A Mechanism for the S[sub(N)]2 Reaction......Page 276
6.7 Transition State Theory: Free-Energy Diagrams......Page 278
6.7A Temperature, Reaction Rate, and the Equilibrium Constant......Page 280
6.8 The Stereochemistry of S[sub(N)]2 Reactions......Page 281
6.9A Multistep Reactions and the Rate-Determining Step......Page 284
6.10 A Mechanism for the S[sub(N)]1 Reaction......Page 285
6.11 Carbocations......Page 286
6.11B The Relative Stabilities of Carbocations......Page 287
6.12A Reactions That Involve Racemization......Page 289
6.12B Solvolysis......Page 291
6.13A The Effect of the Structure of the Substrate......Page 292
6.13B The Effect of the Concentration and Strength of the Nucleophile......Page 296
6.13C Solvent Effects on S[sub(N)]2 Reactions: Polar Protic and Aprotic Solvents......Page 297
6.13D Solvent Effects on S[sub(N)]1 Reactions: The Ionizing Ability of the Solvent......Page 299
6.13E The Nature of the Leaving Group......Page 300
6.14 Organic Synthesis: Functional Group Transformations Using S[sub(N)]2 Reactions......Page 302
6.14A The Unreactivity of Vinylic and Phenyl Halides......Page 305
THE CHEMISTRY OF . . . Biological Methylation: A Biological Nucleophilic Substitution Reaction......Page 304
6.15A Dehydrohalogenation......Page 306
6.16 The E2 Reaction......Page 307
6.17 The E1 Reaction......Page 309
6.18A S[sub(N)]2 versus E2......Page 311
6.18B Tertiary Halides: S[sub(N)]1 versus E1......Page 313
6.19 Overall Summary......Page 314
7 Alkenes and Alkynes I Properties and Synthesis. Elimination Reactions of Alkyl Halides......Page 323
7.2 The (E)–(Z) System for Designating Alkene Diastereomers......Page 324
7.3A Heat of Reaction......Page 326
7.3B Overall Relative Stabilities of Alkenes......Page 327
7.4 Cycloalkenes......Page 328
7.6A How to Favor an E2 Mechanism......Page 329
7.6B Zaitsev’s Rule: Formation of the More Substituted Alkene Is Favored with a Small Base......Page 330
7.6C Formation of the Less Substituted Alkene Using a Bulky Base......Page 332
7.6D The Stereochemistry of E2 Reactions: The Orientation of Groups in the Transition State......Page 333
7.7 Acid-Catalyzed Dehydration of Alcohols......Page 335
7.7A Mechanism for Dehydration of Secondary and Tertiary Alcohols: An E1 Reaction......Page 337
7.7B Carbocation Stability and the Transition State......Page 338
7.7C A Mechanism for Dehydration of Primary Alcohols: An E2 Reaction......Page 340
7.8A Rearrangements during Dehydration of Secondary Alcohols......Page 341
7.8B Rearrangement after Dehydration of a Primary Alcohol......Page 344
7.9 The Acidity of Terminal Alkynes......Page 345
7.10A Laboratory Application of This Alkyne Synthesis......Page 346
7.11 Replacement of the Acetylenic Hydrogen Atom of Terminal Alkynes......Page 348
7.12 Alkylation of Alkynide Anions: Some General Principles of Structure and Reactivity Illustrated......Page 350
THE CHEMISTRY OF . . . Hydrogenation in the Food Industry......Page 351
7.14 Hydrogenation: The Function of the Catalyst......Page 352
7.15A Syn Addition of Hydrogen: Synthesis of cis-Alkenes......Page 353
7.15B Anti Addition of Hydrogen: Synthesis of trans-Alkenes......Page 354
7.16A Why Do Organic Synthesis?......Page 355
7.16B Retrosynthetic Analysis—Planning an Organic Synthesis......Page 356
7.16C Identifying Precursors......Page 357
7.16D Raison d’Etre......Page 360
THE CHEMISTRY OF . . . From the Inorganic to the Organic......Page 359
8 Alkenes and Alkynes II Addition Reactions......Page 369
8.1A How to Understand Additions to Alkenes......Page 370
8.2 Electrophilic Addition of Hydrogen Halides to Alkenes: Mechanism and Markovnikov’s Rule......Page 372
8.2A Theoretical Explanation of Markovnikov’s Rule......Page 374
8.2B Modern Statement of Markovnikov’s Rule......Page 375
8.2D An Exception to Markovnikov’s Rule......Page 376
8.3 Stereochemistry of the Ionic Addition to an Alkene......Page 377
8.5 Addition of Water to Alkenes: Acid-Catalyzed Hydration......Page 378
8.5A Mechanism......Page 379
8.5B Rearrangements......Page 380
8.6A Regioselectivity of Oxymercuration–Demercuration......Page 382
8.6C Mechanism of Oxymercuration......Page 383
8.8 Hydroboration: Synthesis of Alkylboranes......Page 385
8.8A Mechanism of Hydroboration......Page 386
8.8B Stereochemistry of Hydroboration......Page 387
8.9 Oxidation and Hydrolysis of Alkyboranes......Page 388
8.9A Regiochemistry and Stereochemistry of Alkylborane Oxidation and Hydrolysis......Page 389
8.11 Protonolysis of Alkyboranes......Page 391
8.12 Electrophilic Addition of Bromine and Chlorine to Alkenes......Page 392
8.12A Mechanism of Halogen Addition......Page 393
THE CHEMISTRY OF . . . The Sea: A Treasury of Biologically Active Natural Products......Page 395
8.13 Stereospecific Reactions......Page 396
8.14 Halohydrin Formation......Page 397
8.15A Structure and Reactions of Methylene......Page 399
8.15C Carbenoids: The Simmons–Smith Cyclopropane Synthesis......Page 400
8.16A Mechanism for Syn Dihydroxylation of Alkenes......Page 401
8.17A Cleavage with Hot Basic Potassium Permanganate......Page 403
8.17B Cleavage with Ozone......Page 404
8.18 Electrophilic Addition of Bromine and Chlorine to Alkynes......Page 406
8.19 Addition of Hydrogen Halides to Alkynes......Page 407
8.21 How to Plan a Synthesis: Some Approaches and Examples......Page 408
8.21A Retrosynthetic Analysis......Page 409
8.21B Disconnections, Synthons, and Synthetic Equivalents......Page 410
8.21C Stereochemical Considerations......Page 411
9 Nuclear Magnetic Resonance and Mass Spectrometry Tools for Structure Determination......Page 423
9.2 Nuclear Magnetic Resonance (NMR) Spectroscopy......Page 424
9.2A Chemical Shift......Page 425
9.2C Coupling (Signal Splitting)......Page 428
9.3 How to Interpret Proton NMR Spectra......Page 430
9.4 Nuclear Spin: The Origin of the Signal......Page 433
9.5 Detecting the Signal: Fourier Transform NMR Spectrometers......Page 435
9.6 Shielding and Deshielding of Protons......Page 437
9.7 The Chemical Shift......Page 438
9.8A Homotopic and Heterotopic Atoms......Page 439
9.8B Enantiotopic and Diastereotopic Hydrogen Atoms......Page 441
9.9A Vicinal Coupling......Page 443
9.9B Splitting Tree Diagrams and the Origin of Signal Splitting......Page 444
9.9C Coupling Constants—Recognizing Splitting Patterns......Page 448
9.9D The Dependence of Coupling Constants on Dihedral Angle......Page 449
9.9F Analysis of Complex Interactions......Page 450
9.10 Proton NMR Spectra and Rate Processes......Page 453
9.11B One Peak for Each Magnetically Distinct Carbon Atom......Page 455
9.11C [sup(13)]C Chemical Shifts......Page 456
9.11E DEPT [sup(13)]C Spectra......Page 458
9.12 Two-Dimensional (2D) NMR Techniques......Page 460
9.12A COSY Cross-Peak Correlations......Page 461
9.12B HETCOR Cross-Peak Correlations......Page 462
THE CHEMISTRY OF . . . Magnetic Resonance Imaging in Medicine......Page 463
9.13 An Introduction to Mass Spectrometry......Page 464
9.15 Depicting the Molecular Ion......Page 465
9.16A Fragmentation by Cleavage at a Single Bond......Page 466
9.16B Fragmentation of Longer Chain and Branched Alkanes......Page 468
9.16C Fragmentation to Form Resonance-Stabilized Cations......Page 469
9.16D Fragmentation by Cleavage of Two Bonds......Page 472
9.17A Isotopic Peaks and the Molecular Ion......Page 473
9.17B How to Determine the Molecular Formula......Page 474
9.17C High-Resolution Mass Spectrometry......Page 477
9.18A Ionization Techniques: Electron Impact, Electrospray, and MALDI......Page 478
9.19 GC/MS Analysis......Page 480
9.20 Mass Spectrometry of Biomolecules......Page 481
10 Radical Reactions......Page 497
10.1B Reactions of Radicals......Page 498
10.2 Homolytic Bond Dissociation Energies (DH°)......Page 499
10.2A How to Use Homolytic Bond Dissociation Energies to Calculate Heats of Reaction......Page 500
10.2B How to Use Homolytic Bond Dissociation Energies to Determine the Relative Stabilities of Radicals......Page 501
10.3 Reactions of Alkanes with Halogens......Page 503
10.3A Multiple Halogen Substitution......Page 504
10.4 Chlorination of Methane: Mechanism of Reaction......Page 505
10.5 Chlorination of Methane: Energy Changes......Page 508
10.5A The Overall Free-Energy Change......Page 509
10.5B Activation Energies......Page 510
10.5C Reaction of Methane with Other Halogens......Page 513
10.6 Halogenation of Higher Alkanes......Page 515
10.6A Selectivity of Bromine......Page 517
10.7 The Geometry of Alkyl Radicals......Page 518
10.8 Reactions that Generate Tetrahedral Chirality Centers......Page 519
10.8A Generation of a Second Chirality Center in a Radical Halogenation......Page 520
10.9 Radical Addition to Alkenes: The Anti-Markovnikov Addition of Hydrogen Bromide......Page 522
10.10 Radical Polymerization of Alkenes: Chain-Growth Polymers......Page 524
10.11A Molecular Oxygen and Superoxide......Page 528
10.11C Combustion of Alkanes......Page 529
10.11D Autoxidation......Page 531
THE CHEMISTRY OF . . . Calicheamicin γ[sub(1)][Sup(I)]: A Radical Device for Slicing the Backbone of DNA......Page 530
THE CHEMISTRY OF . . . Antioxidants......Page 532
THE CHEMISTRY OF . . . Ozone Depletion and Chlorofluorocarbons (CFCs)......Page 533
See SPECIAL TOPIC B: Chain-Growth Polymers in WileyPLUS......Page 539
11 Alcohols and Ethers Synthesis and Reactions......Page 540
11.1A Nomenclature of Alcohols......Page 541
11.1B Nomenclature of Ethers......Page 542
11.2 Physical Properties of Alcohols and Ethers......Page 543
11.3B Ethanol......Page 545
THE CHEMISTRY OF . . . Ethanol as a Biofuel......Page 546
11.4 Synthesis of Alcohols from Alkenes......Page 547
11.5 Reactions of Alcohols......Page 549
11.6 Alcohols as Acids......Page 551
11.8 Alkyl Halides from the Reaction of Alcohols with Hydrogen Halides......Page 552
11.8A Mechanisms of the Reactions of Alcohols with HX......Page 553
11.9 Alkyl Halides from the Reaction of Alcohols with PBr3 or SOCl2......Page 555
11.10 Tosylates, Mesylates, and Triflates: Leaving Group Derivatives of Alcohols......Page 556
THE CHEMISTRY OF . . . Alkyl Phosphates......Page 559
11.11A Ethers by Intermolecular Dehydration of Alcohols......Page 560
11.11B The Williamson Synthesis of Ethers......Page 561
11.11D tert-Butyl Ethers by Alkylation of Alcohols: Protecting Groups......Page 563
11.11E Silyl Ether Protecting Groups......Page 564
11.12A Cleavage of Ethers......Page 565
11.13A Synthesis of Epoxides: Epoxidation......Page 566
11.13B Stereochemistry of Epoxidation......Page 568
THE CHEMISTRY OF . . . The Sharpless Asymmetric Epoxidation......Page 567
11.14 Reactions of Epoxides......Page 569
11.14A Polyethers from Epoxides......Page 572
THE CHEMISTRY OF . . . Epoxides, Carcinogens, and Biological Oxidation......Page 571
11.15 Anti 1,2-Dihydroxylation of Alkenes via Epoxides......Page 573
11.16 Crown Ethers......Page 575
THE CHEMISTRY OF . . . Transport Antibiotics and Crown Ethers......Page 577
11.17A How Alkenes Can Be Used in Synthesis......Page 578
12 Alcohols From Carbonyl Compounds Oxidation–Reduction and Organometallic Compounds......Page 586
12.1 Structure of the Carbonyl Group......Page 587
12.2 Oxidation–Reduction Reactions in Organic Chemistry......Page 588
12.2A Oxidation States in Organic Chemistry......Page 589
12.3 Alcohols by Reduction of Carbonyl Compounds......Page 590
12.3B Sodium Borohydride......Page 591
THE CHEMISTRY OF . . . Alcohol Dehydrogenase – A Biochemical Hydride Reagent......Page 592
THE CHEMISTRY OF . . . Stereoselective Reductions of Carbonyl Groups......Page 593
12.4B Oxidation of Primary Alcohols to Carboxylic Acids:RCH[sub(2)]OH→RCO[sub(2)]H......Page 595
12.4D Mechanism of Chromate Oxidations......Page 596
12.4E A Chemical Test for Primary and Secondary Alcohols......Page 598
12.5 Organometallic Compounds......Page 599
12.6A Organolithium Compounds......Page 600
12.7A Reactions with Compounds Containing Acidic Hydrogen Atoms......Page 601
12.7C Reactions of Grignard Reagents with Carbonyl Compounds......Page 603
12.8 Alcohols from Grignard Reagents......Page 604
12.8A How to Plan a Grignard Synthesis......Page 607
12.8B Restrictions on the Use of Grignard Reagents......Page 610
12.8D The Use of Sodium Alkynides......Page 611
12.9 Protecting Groups......Page 613
See the First Review Problem Set in WileyPLUS......Page 622
13 Conjugated Unsaturated Systems......Page 623
13.2 Allylic Substitution and the Allyl Radical......Page 624
13.2A Allylic Chlorination (High Temperature)......Page 625
13.2B Allylic Bromination with N-Bromosuccinimide (Low Concentration of Br[sub(2)])......Page 627
13.3 The Stability of the Allyl Radical......Page 628
13.3A Molecular Orbital Description of the Allyl Radical......Page 629
13.3B Resonance Description of the Allyl Radical......Page 630
13.4 The Allyl Cation......Page 632
13.5A Rules for Writing Resonance Structures......Page 633
13.5B Estimating the Relative Stability of Resonance Structures......Page 635
13.6 Alkadienes and Polyunsaturated Hydrocarbons......Page 637
13.7A Bond Lengths of 1,3-Butadiene......Page 638
13.7C Molecular Orbitals of 1,3-Butadiene......Page 639
13.8 The Stability of Conjugated Dienes......Page 640
13.9A The Electromagnetic Spectrum......Page 642
13.9B UV–Vis Spectrophotometers......Page 644
13.9C Absorption Maxima for Nonconjugated and Conjugated Dienes......Page 646
13.9D Analytical Uses of UV–Vis Spectroscopy......Page 649
THE CHEMISTRY OF . . . The Photochemistry of Vision......Page 647
13.10 Electrophilic Attack on Conjugated Dienes: 1,4 Addition......Page 650
13.10A Kinetic Control versus Thermodynamic Control of a Chemical Reaction......Page 652
13.11 The Diels–Alder Reaction: A 1,4-Cycloaddition Reaction of Dienes......Page 654
13.11B Stereochemistry of the Diels–Alder Reaction......Page 656
13.11C Molecular Orbital Considerations That Favor an Endo Transition State......Page 659
THE CHEMISTRY OF . . . Molecules with the Nobel Prize in Their Synthetic Lineage......Page 658
14 Aromatic Compounds......Page 670
14.1 The Discovery of Benzene......Page 671
14.2 Nomenclature of Benzene Derivatives......Page 672
14.3 Reactions of Benzene......Page 675
14.4 The Kekulé Structure for Benzene......Page 676
14.5 The Thermodynamic Stability of Benzene......Page 677
14.6A The Resonance Explanation of the Structure of Benzene......Page 678
14.6B The Molecular Orbital Explanation of the Structure of Benzene......Page 679
14.7A How to Diagram the Relative Energies of π Molecular Orbitals in Monocyclic Systems Based on Hückel’s Rule......Page 681
14.7B The Annulenes......Page 682
14.7C NMR Spectroscopy: Evidence for Electron Delocalization in Aromatic Compounds......Page 684
14.7D Aromatic Ions......Page 685
14.7E Aromatic, Antiaromatic, and Nonaromatic Compounds......Page 687
14.8A Benzenoid Aromatic Compounds......Page 689
14.8C Fullerenes......Page 692
14.9 Heterocylic Aromatic Compounds......Page 693
14.10 Aromatic Compounds in Biochemistry......Page 695
14.11B [sup(13)]C NMR Spectra......Page 698
14.11C Infrared Spectra of Substituted Benzenes......Page 701
THE CHEMISTRY OF . . . Sunscreens (Catching the Sun’s Rays and What Happens to Them......Page 702
14.11E Mass Spectra of Aromatic Compounds......Page 703
15 Reactions of Aromatic Compounds......Page 714
15.1 Electrophilic Aromatic Substitution Reactions......Page 715
15.2 A General Mechanism for Electrophilic Aromatic Substitution......Page 716
15.3 Halogenation of Benzene......Page 718
15.4 Nitration of Benzene......Page 719
15.5 Sulfonation of Benzene......Page 720
15.6 Friedel–Crafts Alkylation......Page 722
15.7 Friedel–Crafts Acylation......Page 723
15.8 Limitations of Friedel–Crafts Reactions......Page 725
15.9 Synthetic Applications of Friedel–Crafts Acylations: The Clemmensen Reduction......Page 728
15.10 Substituents Can Affect Both the Reactivity of the Ring and the Orientation of the Incoming Group......Page 729
15.10B Ortho–Para-Directing Groups and Meta-Directing Groups......Page 730
15.10D Groups: Ortho–Para Directors......Page 731
15.10F Halo Substituents: Deactivating Ortho–Para Directors......Page 733
15.10G Classification of Substituents......Page 734
15.11A Reactivity: The Effect of Electron-Releasing and Electron-Withdrawing Groups......Page 735
15.11B Inductive and Resonance Effects: Theory of Orientation......Page 736
15.11C Meta-Directing Groups......Page 738
15.11D Ortho–Para-Directing Groups......Page 739
15.11E Ortho–Para Direction and Reactivity of Alkylbenzenes......Page 743
15.12 Reactions of the Side Chain of Alkylbenzenes......Page 744
15.12A Benzylic Radicals and Cations......Page 746
THE CHEMISTRY OF . . . Industrial Styrene Synthesis......Page 747
THE CHEMISTRY OF . . . Iodine Incorporation in Thyroxine Biosynthesis......Page 745
15.13B Additions to the Double Bond of Alkenylbenzenes......Page 750
15.13D Oxidation of the Benzene Ring......Page 751
15.14 Synthetic Applications......Page 752
15.14A Use of Protecting and Blocking Groups......Page 753
15.14B Orientation in Disubstituted Benzenes......Page 754
15.15 Allylic and Benzylic Halides in Nucleophilic Substitution Reactions......Page 755
15.16A The Birch Reduction......Page 757
16 Aldehydes and Ketones Nucleophilic Addition to the Carbonyl Group......Page 767
16.2 Nomenclature of Aldehydes and Ketones......Page 768
16.3 Physical Properties......Page 770
16.4A Aldehydes by Oxidation of 1° Alcohols......Page 771
16.4C Aldehydes by Reduction of Acyl Chlorides, Esters, and Nitriles......Page 772
16.5A Ketones from Alkenes, Arenes, and 2° Alcohols......Page 776
16.5B Ketones from Nitriles......Page 777
16.6 Nucleophilic Addition to the Carbon–Oxygen Double Bond......Page 779
16.6C Addition Products Can Undergo Further Reactions......Page 781
16.7A Hemiacetals......Page 782
16.7B Acetals......Page 785
16.7C Acetals Are Used as Protecting Groups......Page 787
16.7D Thioacetals......Page 788
16.8A Imines......Page 789
16.8B Oximes and Hydrazones......Page 790
16.8C Enamines......Page 792
THE CHEMISTRY OF . . . A Very Versatile Vitamin, Pyridoxine (Vitamin B[sub(6)])......Page 791
16.9 The Addition of Hydrogen Cyanide: Cyanohydrins......Page 793
16.10 The Addition of Ylides: The Wittig Reaction......Page 795
16.10A How to Plan a Wittig Synthesis......Page 796
16.10B The Horner–Wadsworth–Emmons Reaction: A Modification of the Wittig Reaction......Page 798
16.12B Tollens’ Test (Silver Mirror Test)......Page 799
16.13A IR Spectra of Aldehydes and Ketones......Page 800
16.13B NMR Spectra of Aldehydes and Ketones......Page 801
16.13D UV Spectra......Page 802
16.14 Summary of Aldehyde and Ketone Addition Reactions......Page 803
17 Carboxylic Acids and Their Derivatives Nucleophilic Addition–Elimination at the Acyl Carbon......Page 817
17.2A Carboxylic Acids......Page 818
17.2C Acidity of Carboxylic Acids......Page 819
17.2D Dicarboxylic Acids......Page 821
17.2E Esters......Page 822
17.2H Amides......Page 823
17.2I Nitriles......Page 824
17.2J Spectroscopic Properties of Acyl Compounds......Page 825
17.3 Preparation of Carboxylic Acids......Page 827
17.4 Acyl Substitution: Nucleophilic Addition–Elimination at the Acyl Carbon......Page 830
17.4A Relative Reactivity of Acyl Compounds......Page 831
17.5A Synthesis of Acyl Chlorides......Page 832
17.5B Reactions of Acyl Chlorides......Page 833
17.6A Synthesis of Carboxylic Acid Anhydrides......Page 834
17.7A Synthesis of Esters: Esterification......Page 835
17.7B Base-Promoted Hydrolysis of Esters: Saponification......Page 838
17.7C Lactones......Page 840
17.8B Amides from Acyl Chlorides......Page 842
17.8C Amides from Carboxylic Anhydrides......Page 843
17.8E Amides from Carboxylic Acids and Ammonium Carboxylates......Page 844
17.8F Hydrolysis of Amides......Page 845
17.8G Nitriles from the Dehydration of Amides......Page 847
THE CHEMISTRY OF . . . Penicillins......Page 849
17.9A Alkyl Chloroformates and Carbamates (Urethanes)......Page 850
17.10 Decarboxylation of Carboxylic Acids......Page 852
17.11 Chemical Tests for Acyl Compounds......Page 854
17.12 Polyesters and Polyamides: Step-Growth Polymers......Page 855
17.13 Summary of the Reactions of Carboxylic Acids and Their Derivatives......Page 856
18 Reactions at the α Carbon of Carbonyl Compounds Enols and Enolates......Page 869
18.1 The Acidity of the α Hydrogens of Carbonyl Compounds: Enolate Anions......Page 870
18.2 Keto and Enol Tautomers......Page 871
18.3A Racemization......Page 872
18.3B Halogenation at the α Carbon......Page 875
18.3C The Haloform Reaction......Page 876
THE CHEMISTRY OF . . . Chloroform in Drinking Water......Page 877
18.4 Lithium Enolates......Page 879
18.4B Direct Alkylation of Ketones via Lithium Enolates......Page 880
18.4C Direct Alkylation of Esters......Page 881
18.5 Enolates of β-Dicarbonyl Compounds......Page 882
18.6 Synthesis of Methyl Ketones: The Acetoacetic Ester Snythesis......Page 883
18.6A Acylation......Page 887
18.7 Synthesis of Substituted Acetic Acids: The Malonic Ester Synthesis......Page 888
18.8 Further Reactions of Active Hydrogen Compounds......Page 891
18.9 Synthesis of Enamines: Stork Enamine Reactions......Page 892
18.10 Summary of Enolate Chemistry......Page 895
See SPECIAL TOPIC C: Step-Growth Polymers in WileyPLUS......Page 906
19 Condensation and Conjugate Addition Reactions of Carbonyl Compounds More Chemistry of Enolates......Page 907
19.2 The Claisen Condensation: The Synthesis of β-Keto Esters......Page 908
19.2A Intramolecular Claisen Condensations: The Dieckmann Condensation......Page 911
19.2B Crossed Claisen Condensations......Page 912
19.3 β-Dicarbonyl Compounds by Acylation of Ketone Enolates......Page 913
19.4 Aldol Reactions: Addition of Enolates and Enols to Aldehydes and Ketones......Page 914
19.4B The Retro-Aldol Reaction......Page 915
19.4C Aldol Condensation Reactions: Dehydration of the Aldol Addition Product......Page 917
19.4D Acid-Catalyzed Aldol Condensations......Page 918
19.4E Synthetic Applications of Aldol Reactions......Page 919
THE CHEMISTRY OF . . . A Retro-Aldol Reaction in Glycolysis—Dividing Assets to Double the ATP Yield......Page 916
19.5 Crossed Aldol Condensations......Page 920
19.5A Crossed Aldol Condensations Using Weak Bases......Page 921
19.5B Crossed Aldol Condensations Using Strong Bases: Lithium Enolates and Directed Aldol Reactions......Page 924
19.6 Cyclizations via Aldol Condensations......Page 926
19.7 Additions to α,β-Unsaturated Aldehydes and Ketones......Page 927
19.7A Conjugate Additions of Enolates: Michael Additions......Page 930
19.7B The Robinson Annulation......Page 931
19.8 The Mannich Reaction......Page 932
THE CHEMISTRY OF . . . A Suicide Enzyme Substrate......Page 933
19.9 Summary of Important Reactions......Page 935
See SPECIAL TOPIC E: Thiol Esters and Lipid Biosynthesis in WileyPLUS......Page 948
20 Amines......Page 949
20.1A Arylamines......Page 950
20.2B Structure of Amines......Page 951
20.3 Basicity of Amines: Amine Salts......Page 953
20.3A Basicity of Arylamines......Page 954
20.3C Amines versus Amides......Page 956
20.3D Aminium Salts and Quaternary Ammonium Salts......Page 957
20.3F Amines as Resolving Agents......Page 958
THE CHEMISTRY OF . . . Biologically Important Amines......Page 960
20.4A Through Nucleophilic Substitution Reactions......Page 962
20.4C Preparation of Primary, Secondary, and Tertiary Amines through Reductive Amination......Page 965
20.4D Preparation of Primary, Secondary, or Tertiary Amines through Reduction of Nitriles, Oximes, and Amides......Page 967
20.4E Preparation of Primary Amines through the Hofmann and Curtius Rearrangements......Page 969
20.5 Reactions of Amines......Page 971
20.5A Oxidation of Amines......Page 972
20.6B Reactions of Primary Arylamines with Nitrous Acid......Page 973
20.7 Replacement Reactions of Arenediazonium Salts......Page 975
THE CHEMISTRY OF . . . N-Nitrosoamines......Page 974
20.7B The Sandmeyer Reaction: Replacement of the Diazonium Group by Cl, Br, or CN......Page 976
20.7F Replacement by Hydrogen: Deamination by Diazotization......Page 977
20.8 Coupling Reactions of Arenediazonium Salts......Page 979
20.9A The Hinsberg Test......Page 981
THE CHEMISTRY OF . . . Chemotherapy and Sulfa Drugs......Page 982
20.11A Chemical Analysis......Page 985
20.11B Spectroscopic Analysis......Page 986
20.12A The Hofmann Elimination......Page 987
20.13 Summary of Preparations and Reactions of Amines......Page 988
See SPECIAL TOPIC F: Alkaloids in WileyPLUS......Page 1001
21 Phenols and Aryl Halides Nucleophilic Aromatic Substitution......Page 1002
21.1A Nomenclature of Phenols......Page 1003
21.3 Physical Properties of Phenols......Page 1004
21.4B Industrial Syntheses......Page 1005
21.5 Reactions of Phenols as Acids......Page 20
21.5A Strength of Phenols as Acids......Page 1007
21.5B Distinguishing and Separating Phenols from Alcohols and Carboxylic Acids......Page 1009
21.6A Phenols in the Williamson Synthesis......Page 1010
21.8 Reactions of the Benzene Ring of Phenols......Page 1011
THE CHEMISTRY OF . . . Polyketide Anticancer Antibiotic Biosynthesis......Page 1013
21.9 The Claisen Rearrangement......Page 1015
21.10 Quinones......Page 1016
THE CHEMISTRY OF . . . The Bombardier Beetle’s Noxious Spray......Page 1017
21.11 Aryl Halides and Nucleophilic Aromatic Substitution......Page 1018
21.11A Nucleophilic Aromatic Substitution by Addition–Elimination: The SNAr Mechanism......Page 1019
21.11B Nucleophilic Aromatic Substitution through an Elimination–Addition Mechanism: Benzyne......Page 1022
21.11C Phenylation......Page 1025
THE CHEMISTRY OF . . . Bacterial Dehalogenation of a PCB Derivative......Page 1021
21.12 Spectroscopic Analysis of Phenols and Aryl Halides......Page 1026
THE CHEMISTRY OF . . . Aryl Halides: Their Uses and Environmental Concerns......Page 1027
See SPECIAL TOPIC H: Electrocyclic and Cycloaddition Reactions in WileyPLUS......Page 1037
22 Carbohydrates......Page 1038
22.1A Classification of Carbohydrates......Page 1039
22.1B Photosynthesis and Carbohydrate Metabolism......Page 1040
22.2B D and L Designations of Monosaccharides......Page 1042
22.2C Structural Formulas for Monosaccharides......Page 1043
22.3 Mutarotation......Page 1047
22.4 Glycoside Formation......Page 1048
22.5A Enolization, Tautomerization, and Isomerization......Page 1051
22.5C Formation of Ethers......Page 1052
22.5D Conversion to Esters......Page 1053
22.6A Benedict’s or Tollens’ Reagents: Reducing Sugars......Page 1054
22.6B Bromine Water: The Synthesis of Aldonic Acids......Page 1055
22.6C Nitric Acid Oxidation: Aldaric Acids......Page 1056
22.6D Periodate Oxidations: Oxidative Cleavage of Polyhydroxy Compounds......Page 1058
22.8 Reactions of Monosaccharides with Phenylhydrazine: Osazones......Page 1060
22.9A Kiliani–Fischer Synthesis......Page 1061
22.10 The D Family of Aldoses......Page 1063
22.11 Fischer’s Proof of the Configuration of D-(+)-Glucose......Page 1065
22.12A Sucrose......Page 1067
22.12B Maltose......Page 1068
22.12C Cellobiose......Page 1069
22.13 Polysaccharides......Page 1071
THE CHEMISTRY OF . . . Artificial Sweeteners (How Sweet It Is)......Page 1070
22.13A Starch......Page 1072
22.13B Glycogen......Page 1073
22.13C Cellulose......Page 1074
22.14 Other Biologically Important Sugars......Page 1075
22.15A Glycosylamines......Page 1076
22.15B Amino Sugars......Page 1077
22.16 Glycolipids and Glycoproteins of the Cell Surface: Cell Recognition and theImmune System......Page 1078
22.18 Summary of Reactions of Carbohydrates......Page 1080
23 Lipids......Page 1088
23.1 Introduction......Page 1089
23.2 Fatty Acids and Triacylglycerols......Page 1090
23.2A Hydrogenation of Triacylglycerols......Page 1092
THE CHEMISTRY OF . . . Olestra and Other Fat Substitutes......Page 1093
23.2C Saponification of Triacylglycerols......Page 1094
23.2E Reactions of the Alkenyl Chain of Unsaturated Fatty Acids......Page 1097
THE CHEMISTRY OF . . . Self-Assembled Monolayers—Lipids in Materials Science andBioengineering......Page 1098
23.3 Terpenes and Terpenoids......Page 1099
23.4 Steroids......Page 1102
23.4A Structure and Systematic Nomenclature of Steroids......Page 1103
23.4B Cholesterol......Page 1104
23.4C Sex Hormones......Page 1106
23.4E D Vitamins......Page 1108
23.4F Other Steroids......Page 1109
23.4G Reactions of Steroids......Page 1110
23.5 Prostaglandins......Page 1111
23.6A Phosphatides......Page 1112
THE CHEMISTRY OF . . . STEALTH® Liposomes for Drug Delivery......Page 1115
23.7 Waxes......Page 1116
24 Amino Acids and Proteins......Page 1122
24.1 Introduction......Page 1123
24.2A Structures and Names......Page 1124
24.2C Amino Acids as Dipolar Ions......Page 1127
24.3A From Potassium Phthalimide......Page 1130
24.3C Resolution of DL-Amino Acids......Page 1131
24.4 Polypeptides and Proteins......Page 1132
24.4A Hydrolysis......Page 1133
24.5A Edman Degradation......Page 1135
24.5B Sanger N-Terminal Analysis......Page 1136
24.5D Complete Sequence Analysis......Page 1137
24.5E Peptide Sequencing Using Mass Spectrometry and Sequence Databases......Page 1138
24.6A Oxytocin and Vasopressin......Page 1139
24.6B Insulin......Page 1140
THE CHEMISTRY OF . . . Sickle-Cell Anemia......Page 1141
24.7 Polypeptide and Protein Synthesis......Page 1142
24.7A Protecting Groups......Page 1143
24.7C Peptide Synthesis......Page 1145
24.7D Automated Peptide Synthesis......Page 1146
24.8A Secondary Structure......Page 1148
24.8C Quaternary Structure......Page 1152
24.9 Introduction to Enzymes......Page 1153
24.10 Lysozyme: Mode of Action of an Enzyme......Page 1154
THE CHEMISTRY OF . . . Carbonic Anhydrase: Shuttling the Protons......Page 1157
24.11 Serine Proteases......Page 1158
24.12 Hemoglobin: A Conjugated Protein......Page 1160
THE CHEMISTRY OF . . . Some Catalytic Antibodies......Page 1161
24.13B Analysis......Page 1163
24.14 Proteomics......Page 1164
25 Nucleic Acids and Protein Synthesis......Page 1169
25.1 Introduction......Page 1170
25.2 Nucleotides and Nucleosides......Page 1171
25.3 Laboratory Synthesis of Nucleosides and Nucleotides......Page 1175
25.4A Primary Structure......Page 1177
25.4B Secondary Structure......Page 1178
25.4C Replication of DNA......Page 1182
25.5 RNA and Protein Synthesis......Page 1184
25.5A Messenger RNA Synthesis—Transcription......Page 1185
25.5B Ribosomes—rRNA......Page 1186
25.5C Transfer RNA......Page 1187
25.5D The Genetic Code......Page 1188
25.5E Translation......Page 1190
25.6A DNA Sequencing by the Chain-Terminating (Dideoxynucleotide) Method......Page 1193
25.7 Laboratory Synthesis of Oligonucleotides......Page 1195
25.8 The Polymerase Chain Reaction......Page 1196
25.9 Sequencing of the Human Genome: An Instruction Book for the Molecules of Life......Page 1200
Answers to Selected Problems......Page 1203
Glossary......Page 1212
Photo Credits......Page 1234
Index......Page 1236