Organic Chemistry

Cover......Page 1
Title Page......Page 3
Copyright......Page 4
Brief Contents......Page 5
Contents......Page 6
Preface......Page 15
The Development Story......Page 20
1 A Review of General Chemistry: Electrons, Bonds, and Molecular Properties......Page 27
1.1 Introduction to Organic Chemistry......Page 28
1.2 The Structural Theory of Matter......Page 29
What Are Bonds?......Page 30
Drawing the Lewis Structure of an Atom......Page 31
Drawing the Lewis Structure of a Small Molecule......Page 32
1.4 Identifying Formal Charges......Page 34
1.5 Induction and Polar Covalent Bonds......Page 35
Quantum Mechanics......Page 38
Phases of Atomic Orbitals......Page 39
Filling Atomic Orbitals with Electrons......Page 40
1.7 Valence Bond Theory......Page 42
1.8 Molecular Orbital Theory......Page 43
Methane and sp³ Hybridization......Page 44
Double Bonds and sp²  Hybridization......Page 46
Triple Bonds and sp Hybridization......Page 48
Bond Strength and Bond Length......Page 50
1.10 VSEPR Theory: Predicting Geometry......Page 51
Geometries Resulting from sp³ Hybridization......Page 52
Geometries Resulting from sp² Hybridization......Page 53
Geometry Resulting from sp Hybridization......Page 54
1.11 Dipole Moments and Molecular Polarity......Page 56
Hydrogen Bonding......Page 60
PRACTICALLY SPEAKING: Biomimicry and Gecko Feet......Page 62
MEDICALLY SPEAKING: Drug-Receptor Interactions......Page 66
Dry Cleaning......Page 67
Review of Concepts Vocabulary......Page 68
SkillBuilder Review......Page 69
Practice Problems......Page 72
Challenge Problems......Page 74
2 Molecular Representations......Page 75
2.1 Molecular Representations......Page 76
How to Read Bond-Line Structures......Page 78
How to Draw Bond-Line Structures......Page 81
2.3 Identifying Functional Groups......Page 83
2.4 Carbon Atoms with Formal Charges......Page 84
2.5 Identifying Lone Pairs......Page 85
2.6 Three-Dimensional Bond-Line Structures......Page 89
MEDICALLY SPEAKING: Identifying the Pharmacophore......Page 90
The Inadequacy of Bond-Line Structures......Page 92
Resonance......Page 93
2.8 Curved Arrows......Page 94
2.9 Formal Charges in Resonance Structures......Page 97
2.10 Drawing Resonance Structures via Pattern Recognition......Page 99
2.11 Assessing Relative Importance of Resonance Structures......Page 105
Localized Lone Pairs......Page 109
Key Terminology......Page 113
SkillBuilder Review......Page 114
Practice Problems......Page 116
Integrated Problems......Page 118
Challenge Problems......Page 119
3 Acids and Bases......Page 120
3.2 Flow of Electron Density: Curved Arrow Notation......Page 121
MEDICALLY SPEAKING: Antacids and Heartburn......Page 124
Using pK[sub(a)] Values to Compare Acidity......Page 125
Using pK[sub(a)]  Values to Compare Basicity......Page 128
Using pK[sub(a)]  Values to Predict the Position of Equilibrium......Page 129
MEDICALLY SPEAKING: Drug Distribution and pK[sub(a)]......Page 132
Conjugate Base Stability......Page 133
Factors Affecting the Stability of Negative Charges......Page 134
Ranking the Factors That Affect the Stability of Negative Charges......Page 143
3.5 Position of Equilibrium and Choice of Reagents......Page 146
3.6 Choice of Solvent......Page 149
3.7 Solvating Effects......Page 150
3.8 Counterions......Page 151
PRACTICALLY SPEAKING: Baking Soda versus Baking Powder......Page 152
3.9 Lewis Acids and Bases......Page 153
Review of Concepts and Vocabulary......Page 154
SkillBuilder Review......Page 155
Practice Problems......Page 158
Integrated Problems......Page 160
Challenge Problems......Page 161
4 Alkanes and Cycloalkanes......Page 162
An Introduction to IUPAC Nomenclature......Page 163
Selecting the Parent Chain......Page 164
Naming Substituents......Page 166
Naming Complex Substituents......Page 168
Assembling the Systematic Name of an Alkane......Page 171
Naming Bicyclic Compounds......Page 173
MEDICALLY SPEAKING: Naming Drugs......Page 176
4.3 Constitutional Isomers of Alkanes......Page 177
4.4 Relative Stability of Isomeric Alkanes......Page 178
4.5 Sources and Uses of Alkanes......Page 179
4.6 Drawing Newman Projections......Page 181
4.7 Conformational Analysis of Ethane and Propane......Page 183
4.8 Conformational Analysis of Butane......Page 185
MEDICALLY SPEAKING: Drugs and Their Conformations......Page 189
4.9 Cycloalkanes......Page 190
Cyclopentane......Page 191
4.10 Conformations of Cyclohexane......Page 192
Drawing the Skeleton of a Chair Conformation......Page 193
Drawing Axial and Equatorial Substituents......Page 194
Drawing Both Chair Conformations......Page 195
Comparing the Stability of Both Chair Conformations......Page 197
Drawing Both Chair Conformations......Page 198
Comparing the Stability of Chair Conformations......Page 201
4.14 cis-trans Stereoisomerism......Page 203
4.15 Polycyclic Systems......Page 204
Review of Concepts and Vocabulary......Page 205
Key Terminology......Page 206
SkillBuilder Review......Page 207
Practice Problems......Page 210
Integrated Problems......Page 212
Challenge Problems......Page 213
5 Stereoisomerism......Page 214
5.1 Overview of Isomerism......Page 215
Chirality......Page 218
Chirality Centers......Page 219
Enantiomers......Page 221
PRACTICALLY SPEAKING: The Sense of Smell......Page 224
5.3 Designating Configuration Using the Cahn-Ingold-Prelog System......Page 225
Assigning Priorities to All Four Groups......Page 226
Rotating the molecule......Page 227
MEDICALLY SPEAKING: Chiral Drugs......Page 230
Plane-Polarized light......Page 231
Polarimetry......Page 232
Specific Rotation......Page 233
Enantiomeric Excess......Page 235
5.5 Stereoisomeric Relationships: Enantiomers and Diastereomers......Page 236
Rotational Symmetry Versus Reflectional Symmetry......Page 240
Meso Compounds......Page 242
5.7 Fischer Projections......Page 245
5.8 Conformationally Mobile Systems......Page 247
Resolution via Crystallization......Page 248
Chiral Column Chromatography......Page 249
Review of Concepts & Vocabulary......Page 250
SkillBuilder Review......Page 251
Practice Problems......Page 253
Integrated Problems......Page 257
Challenge Problems......Page 258
6 Chemical Reactivity and Mechanisms......Page 259
6.1 Enthalpy......Page 260
6.2 Entropy......Page 263
6.3 Gibbs Free Energy......Page 266
PRACTICALLY SPEAKING: Explosives......Page 267
PRACTICALLY SPEAKING: Do Living Organisms Violate the Second Law of Thermodynamics?......Page 268
6.4 Equilibria......Page 269
Rate Equations......Page 271
Factors Affecting the Rate Constant......Page 272
MEDICALLY SPEAKING Nitroglycerin: An Explosive with Medicinal Properties......Page 274
PRACTICALLY SPEAKING: Beer-Making......Page 275
Kinetics Versus Thermodynamics......Page 276
Transition States Versus intermediates......Page 277
The Hammond Postulate......Page 278
6.7 Nucleophiles and Electrophiles......Page 279
Nucleophiles......Page 280
Electrophiles......Page 281
Nucleophilic Attack......Page 283
Loss of a Leaving Group......Page 284
Proton Transfers......Page 285
Rearrangements......Page 286
6.9 Combining the Patterns of Arrow Pushing......Page 289
6.10 Drawing Curved Arrows......Page 291
6.11 Carbocation Rearrangements......Page 294
Review of Concepts and Vocabulary......Page 296
SkillBuilder Review......Page 297
Practice Problems......Page 299
Integrated Problems......Page 305
Challenge Problems......Page 306
7 Substitution Reactions......Page 307
7.1 Introduction to Substitution Reactions......Page 308
Naming Halogenated Organic Compounds......Page 309
Uses of Organohalides......Page 310
7.3 Possible Mechanisms for Substitution Reactions......Page 313
Kinetics......Page 316
Stereospecificity of S[sub N]2 Reactions......Page 317
Structure of the Substrate......Page 318
PRACTICALLY SPEAKING: S[sub N]2 Reactions in Biological Systems—Methylation......Page 322
Kinetics......Page 323
Structure of Substrate......Page 325
Stereochemistry of SN1 Reactions......Page 327
7.6 Drawing the Complete Mechanism of an SN1 Reaction......Page 329
Proton Transfer at the Beginning of an SN1 Process......Page 330
Proton Transfer at the end of an SN1 Process......Page 331
Carbocation Rearrangements during an SN1 Process......Page 332
Summary of the SN1 Process and Its energy Diagram......Page 333
Proton Transfer at the Beginning of an SN2 Process......Page 337
Proton Transfer Before and After an SN2 Process......Page 338
The Substrate......Page 340
The Leaving Group......Page 342
Solvent Effects......Page 344
Summary of Factors Affecting SN2 and SN1 Mechanisms......Page 346
7.9 Selecting Reagents to Accomplish Functional Group Transformation......Page 347
MEDICALLY SPEAKING: Pharmacology and Drug Design......Page 350
Review of Concepts and Vocabulary......Page 352
SkillBuilder Review......Page 353
Practice Problems......Page 355
Challenge Problems......Page 358
8 Alkenes: Structure and Preparation via Elimination Reactions......Page 359
8.2 Alkenes in Nature and in Industry......Page 360
PRACTICALLY SPEAKING: Pheromones to Control Insect Populations......Page 361
8.3 Nomenclature of Alkenes......Page 363
Using cis and trans Designations......Page 366
Using E and Z Designations......Page 367
8.5 Alkene Stability......Page 370
8.6 Possible Mechanisms for Elimination......Page 372
Kinetic Evidence for a Concerted Mechanism......Page 374
Effect of Substrate......Page 375
Regioselectivity of E2 Reactions......Page 377
Stereoselectivity of E2 Reactions......Page 380
Stereospecificity of E2 Reactions on Substituted Cyclohexanes......Page 384
8.8 Drawing the Products of an E2 Reaction......Page 387
Kinetic Evidence for a Stepwise Mechanism......Page 388
Effect of Substrate......Page 389
Regioselectivity of E1 Reactions......Page 391
Stereoselectivity of E1 Reactions......Page 392
Proton Transfer at the Beginning of an E1 Mechanism......Page 393
Carbocation Rearrangement During an E1 Mechanism......Page 394
An E1 Mechanism Can Have Many Steps......Page 395
8.11 Drawing the Complete Mechanism of an E2 Process......Page 398
8.12 Substitution vs. Elimination: Identifying the Reagent......Page 399
Basicity......Page 400
Nucleophilicity vs. Basicity......Page 401
Possible Outcomes for Reagents That Function Only as Bases......Page 403
Possible Outcomes for Reagents That Are Weak Bases and Weak Nucleophiles......Page 404
8.14 Substitution vs. Elimination: Predicting the Products......Page 407
Review of Concepts and Vocabulary......Page 410
Key Terminology......Page 411
SkillBuilder Review......Page 412
Practice Problems......Page 415
Integrated Problems......Page 418
Challenge Problems......Page 419
9 Addition Reactions of Alkenes......Page 420
9.1 Introduction to Addition Reactions......Page 421
9.2 Addition vs. Elimination: A Thermodynamic Perspective......Page 422
Regioselectivity of Hydrohalogenation......Page 423
A Mechanism for Hydrohalogenation......Page 425
Stereochemistry of Hydrohalogenation......Page 428
Hydrohalogenation with Carbocation Rearrangements......Page 429
PRACTICALLY SPEAKING: Cationic Polymerization and Polystyrene......Page 431
Mechanism and Source of Regioselectivity......Page 432
Controlling the Position of Equilibrium......Page 433
Stereochemistry of Acid-Catalyzed Hydration......Page 434
9.5 Oxymercuration-Demercuration......Page 436
An Introduction to Hydroboration-Oxidation......Page 438
Reagents for Hydroboration-Oxidation......Page 439
Regioselectivity of Hydroboration-Oxidation......Page 440
Stereospecificity of Hydroboration-Oxidation......Page 442
Stereospecificity of Catalytic Hydrogenation......Page 444
The Role of the Catalyst in Catalytic Hydrogenation......Page 445
Asymmetric Catalytic Hydrogenation......Page 448
PRACTICALLY SPEAKING: Partially Hydrogenated Fats and Oils......Page 450
Experimental Observations......Page 451
A Mechanism for Halogenation......Page 452
Halohydrin Formation......Page 453
Regiochemistry of Halohydrin Formation......Page 454
9.9 Anti Dihydroxylation......Page 456
9.10 Syn Dihydroxylation......Page 459
9.11 Oxidative Cleavage......Page 460
9.12 Predicting Products of an Addition Reaction......Page 462
One-Step Syntheses......Page 464
Changing the Position of a Leaving Group......Page 466
Changing the Position of a π Bond......Page 468
Review of Concepts and Vocabulary......Page 470
Key Terminology......Page 471
SkillBuilder Review......Page 472
Practice Problems......Page 475
Integrated Problems......Page 478
Challenge Problems......Page 479
10 Alkynes......Page 480
Alkynes in Industry and Nature......Page 481
MEDICALLY SPEAKING: The Role of Molecular Rigidity......Page 482
10.2 Nomenclature of Alkynes......Page 483
10.3 Acidity of Acetylene and Terminal Alkynes......Page 486
10.4 Preparing Alkynes......Page 489
Catalytic Hydrogenation......Page 490
Dissolving Metal Reduction......Page 492
Catalytic Hydrogenation vs. Dissolving Metal Reduction......Page 493
A Mechanism for Hydrohalogenation......Page 494
Interconversion of Dihalides and Alkynes......Page 496
Acid-Catalyzed Hydration of Alkynes......Page 497
Hydroboration-Oxidation of Alkynes......Page 500
Controlling the Regiochemistry of Alkyne Hydration......Page 501
10.9 Ozonolysis of Alkynes......Page 503
10.10 Alkylation of Terminal Alkynes......Page 504
10.11 Synthesis Strategies......Page 505
Review of Reactions......Page 508
Key Terminology......Page 509
SkillBuilder Review......Page 510
Practice Problems......Page 512
Integrated Problems......Page 514
Challenge Problems......Page 515
11 Radical Reactions......Page 516
Structure and Geometry of Radicals......Page 517
Resonance Structures of Radicals......Page 519
11.2 Common Patterns in Radical Mechanisms......Page 522
A Radical Mechanism for Chlorination of Methane......Page 526
Radical Initiators......Page 528
11.4 Thermodynamic Considerations for Halogenation Reactions......Page 529
11.5 Regioselectivity of Halogenation......Page 532
11.6 Stereochemistry of Halogenation......Page 535
Halogenation at an Existing Chirality Center......Page 536
11.7 Allylic Bromination......Page 538
11.8 Atmospheric Chemistry and the Ozone Layer......Page 540
PRACTICALLY SPEAKING: Fighting Fires with Chemicals......Page 542
Autooxidation......Page 543
Antioxidants as Food Additives......Page 545
MEDICALLY SPEAKING: Why is an Overdose of Acetaminophen Fatal?......Page 546
Regiochemical Observations......Page 547
A Mechanism for Anti-Markovnikov Addition of HX Br......Page 548
Thermodynamic Considerations......Page 549
Stereochemistry for Radical Addition of HBr......Page 550
Radical Polymerization of Ethylene......Page 551
Radical Polymerization of a Substituted Ethylene......Page 553
11.13 Halogenation as a Synthetic Technique......Page 554
Review of Concepts and Vocabulary......Page 555
SkillBuilder Review......Page 556
Practice Problems......Page 558
Integrated Problems......Page 560
Challenge Problems......Page 561
12 Synthesis......Page 562
12.1 One-Step Syntheses......Page 563
12.2 Functional Group Transformations......Page 564
12.3 Reactions that Change the Carbon Skeleton......Page 569
MEDICALLY SPEAKING: Vitamins......Page 571
12.4 How to Approach a Synthesis Problem......Page 572
MEDICALLY SPEAKING: The Total Synthesis of Vitamin B₁₂......Page 574
12.5 Retrosynthetic Analysis......Page 575
PRACTICALLY SPEAKING: Retrosynthetic Analysis......Page 9
Organizing a Synthetic “Toolbox” of Reactions......Page 583
Multiple Correct Answers......Page 584
SkillBuilder Review......Page 585
Practice Problems......Page 587
Integrated Problems......Page 588
Challenge Problems......Page 589
13 Alcohols and Phenols......Page 590
13.1 Structure and Properties of Alcohols......Page 591
Nomenclature......Page 592
Physical Properties of Alcohols......Page 595
MEDICALLY SPEAKING: Chain Length as a Factor in Drug Design......Page 596
Reagents for Deprotonating an Alcohol......Page 597
Factors Affecting the Acidity of Alcohols and Phenols......Page 598
Substitution Reactions......Page 600
13.4 Preparation of Alcohols via Reduction......Page 601
Oxidation States......Page 602
Reducing Agents......Page 604
13.5 Preparation of Diols......Page 609
13.6 Preparation of Alcohols via Grignard Reagents......Page 610
13.7 Protection of Alcohols......Page 614
13.8 Preparation of Phenols......Page 616
SN2 Reactions with Alcohols......Page 617
E1 and E2 Reactions with Alcohols......Page 621
13.10 Reactions of Alcohols: Oxidation......Page 623
PRACTICALLY SPEAKING: Breath Tests to Measure Blood Alcohol Level......Page 624
13.11 Biological Redox Reactions......Page 627
PRACTICALLY SPEAKING: Biological Oxidation of Methanol and Ethanol......Page 628
13.12 Oxidation of Phenol......Page 629
Functional Group interconversion......Page 630
C-C Bond Formation......Page 634
Functional Group Transformations and C-C Bond Formation......Page 635
Review of Reactions......Page 637
Review of Concepts and Vocabulary......Page 638
SkillBuilder Review......Page 639
Practice Problems......Page 642
Integrated Problems......Page 645
Challenge Problems......Page 647
14 Ethers and Epoxides; Thiols and Sulfides......Page 648
14.2 Nomenclature of Ethers......Page 649
14.3 Structure and Properties of Ethers......Page 652
MEDICALLY SPEAKING: Ethers as Inhalation Anesthetics......Page 653
14.4 Crown Ethers......Page 654
Industrial Preparation of diethyl Ether......Page 656
Williamson Ether Synthesis......Page 657
Acidic Cleavage......Page 659
Autooxidation......Page 661
14.7 Nomenclature of Epoxides......Page 662
Preparation with Peroxy Acids......Page 663
Preparation from Halohydrins......Page 664
MEDICALLY SPEAKING: Active Metabolites and Drug Interactions......Page 666
14.9 Enantioselective Epoxidation......Page 667
Reactions of Epoxides with Strong Nucleophiles......Page 669
Acid-Catalyzed Ring Opening......Page 672
MEDICALLY SPEAKING: Cigarette Smoke and Carcinogenic......Page 677
Thiols......Page 678
Sulfides......Page 680
Installing Two Adjacent Functional Groups......Page 682
Grignard Reagents: Controlling the location of the Resulting Functional Group......Page 684
Review of Reactions......Page 687
Review of Concepts and Vocabulary......Page 689
SkillBuilder Review......Page 690
Practice Problems......Page 692
Integrated Problems......Page 695
Challenge Problems......Page 696
15 Infrared Spectroscopy and Mass Spectrometry......Page 697
The Nature of Light......Page 698
The Interaction between Light and Matter......Page 699
Vibrational Excitation......Page 700
Identification of Functional Groups with IR Spectroscopy......Page 701
The General Shape of an IR Absorbance Spectrum......Page 702
Hooke’s Law......Page 703
Effect of Hybridization States on Wavenumber of Absorption......Page 704
Effect of Resonance on Wavenumber of Absorption......Page 705
15.4 Signal Characteristics: Intensity......Page 707
Effects of Hydrogen Bonding......Page 710
Amines: Symmetrical vs. Asymmetrical......Page 713
15.6 Analyzing an IR Spectrum......Page 714
15.7 Using IR Spectroscopy to Distinguish between Two Compounds......Page 719
15.8 Introduction to Mass Spectrometry......Page 721
PRACTICALLY SPEAKING: Mass Spectrometry for Detecting Explosives......Page 722
15.9 Analyzing the (M)⁺• Peak......Page 723
15.10 Analyzing the (M+1)⁺• Peak......Page 724
15.11 Analyzing the (M+2)⁺● Peak......Page 726
Fragmentation of Alkanes......Page 728
Fragmentation of Alcohols......Page 729
Fragmentation of ketones and Aldehydes......Page 730
15.13 High Resolution Mass Spectrometry......Page 731
15.14 Gas Chromatography—Mass Spectrometry......Page 733
15.16 Hydrogen Deficiency Index: Degrees of Unsaturation......Page 734
Review of Concepts and Vocabulary......Page 737
SkillBuilder Review......Page 739
Practice Problems......Page 740
Integrated Problems......Page 742
Challenge Problems......Page 743
16 Nuclear Magnetic Resonance Spectroscopy......Page 744
16.1 Introduction to NMR Spectroscopy......Page 745
Magnetic Field Strength......Page 747
NMR Spectrometers......Page 748
Chemical Equivalence......Page 749
Variable-Temperature NMR......Page 755
Chemical Shift Values......Page 756
Inductive Effects......Page 757
Anisotropic Effects......Page 760
16.6 Integration......Page 762
Coupling......Page 765
Coupling Constant......Page 769
Pattern Recognition......Page 770
Complex Splitting......Page 771
Protons That lack Observable Coupling Constants......Page 772
16.8 Drawing the Expected ¹H NMR Spectrum of a Compound......Page 773
16.9 Using 1H NMR Spectroscopy to Distinguish between Compounds......Page 775
16.10 Analyzing a ¹H NMR Spectrum......Page 777
16.11 Acquiring a ¹³C NMR Spectrum......Page 780
16.12 Chemical Shifts in ¹³C NMR Spectroscopy......Page 781
16.13 DEPT ¹³C NMR Spectroscopy......Page 783
MEDICALLY SPEAKING: Magnetic Resonance Imaging (MRI)......Page 785
Review of Concepts and Vocabulary......Page 786
SkillBuilder Review......Page 787
Practice Problems......Page 789
Integrated Problems......Page 792
Challenge Problems......Page 793
17 Conjugated Pi Systems and Pericyclic Reactions......Page 794
17.1 Classes of Dienes......Page 795
Stability......Page 796
Conformations of 1,3-Butadiene......Page 797
Molecular Orbitals of Butadiene......Page 798
Molecular Orbitals of Hexatriene......Page 800
Addition of HX Across 1,3-Butadiene......Page 802
17.5 Thermodynamic Control vs. Kinetic Control......Page 805
PRACTICALLY SPEAKING: Natural and Synthetic Rubbers......Page 808
17.6 An Introduction to Pericyclic Reactions......Page 809
Thermodynamic Considerations......Page 810
The Dienophile......Page 811
The Diene......Page 813
Endo Preference......Page 814
17.8 MO Description of Cycloadditions......Page 816
An Introduction to Electrocyclic Reactions......Page 818
The Stereochemistry of Thermal Electrocyclic Reactions......Page 819
Stereochemistry of Photochemical Electrocyclic Reactions......Page 821
The Claisen Rearrangement......Page 824
The Information in a UV-Vis Spectrum......Page 826
Woodward-Fieser Rules......Page 828
PRACTICALLY SPEAKING: Sunscreens......Page 831
PRACTICALLY SPEAKING: Bleach......Page 832
17.13 The Chemistry of Vision......Page 833
Review of Reactions......Page 834
Review of Concepts and Vocabulary......Page 836
SkillBuilder Review......Page 837
Practice Problems......Page 839
Integrated Problems......Page 841
Challenge Problems......Page 842
18 Aromatic Compounds......Page 843
18.1 Introduction to Aromatic Compounds......Page 844
Monosubstituted Derivatives of Benzene......Page 845
Disubstituted Derivatives of Benzene......Page 846
Evidence for Unusual Stability......Page 849
Source of Stability......Page 851
Hückel’s Rule......Page 852
MO Theory and Frost Circles......Page 853
PRACTICALLY SPEAKING: Molecular Cages......Page 854
The Criteria for Aromaticity......Page 856
Aromatic lons......Page 857
Aromatic Heterocycles......Page 859
Polycyclic Aromatic Compounds......Page 862
MEDICALLY SPEAKING: The Development of Nonsedating Antihistamines......Page 863
Oxidation......Page 865
elimination Reactions of Benzylic Halides......Page 866
Summary of Reactions at the Benzylic Position......Page 867
Birch Reduction......Page 869
IR Spectroscopy......Page 872
¹H NMR Spectroscopy......Page 873
¹³C NMR Spectroscopy......Page 874
PRACTICALLY SPEAKING: Buckyballs and Nanotubes......Page 875
Key Terminology......Page 876
Review of Concepts and Vocabulary......Page 877
SkillBuilder Review......Page 878
Practice Problems......Page 879
Integrated Problems......Page 882
Challenge Problems......Page 883
19 Aromatic Substitution Reactions......Page 884
19.1 Introduction to Electrophilic Aromatic Substitution......Page 885
19.2 Halogenation......Page 886
19.3 Sulfonation......Page 889
PRACTICALLY SPEAKING: What Are Those Colors in Fruity Pebbles?......Page 891
19.4 Nitration......Page 892
19.5 Friedel–Crafts Alkylation......Page 893
MEDICALLY SPEAKING: The Discovery of Prodrugs......Page 894
19.6 Friedel–Crafts Acylation......Page 897
Nitration of Toluene......Page 899
Nitration of Anisole......Page 901
19.8 Deactivating Groups......Page 903
19.9 Halogens: The Exception......Page 905
Activators......Page 907
Deactivators......Page 908
Directing Effects......Page 910
Steric effects......Page 912
Blocking Groups......Page 914
Disubstituted Benzene Rings......Page 917
Polysubstituted Benzene Rings......Page 921
19.13 Nucleophilic Aromatic Substitution......Page 924
19.14 Elimination-Addition......Page 926
19.15 Identifying the Mechanism of an Aromatic Substitution Reaction......Page 928
Review of Concepts and Vocabulary......Page 930
SkillBuilder Review......Page 932
Practice Problems......Page 934
Challenge Problems......Page 939
20 Aldehydes and Ketones......Page 941
20.1 Introduction to Aldehydes and Ketones......Page 942
Nomenclature of Aldehydes......Page 943
Nomenclature of Ketones......Page 944
20.3 Preparing Aldehydes and Ketones: A Review......Page 946
20.4 Introduction to Nucleophilic Addition Reactions......Page 947
Hydrate Formation......Page 949
Acetal Formation......Page 951
Acetals as Protecting Groups......Page 955
MEDICALLY SPEAKING: Acetals as Prodrugs......Page 956
Primary Amines......Page 957
PRACTICALLY SPEAKING: Beta-carotene and Vision......Page 961
Secondary Amines......Page 962
Wolff-Kishner Reduction......Page 965
20.7 Mechanism Strategies......Page 966
MEDICALLY SPEAKING: Prodrugs......Page 970
20.8 Sulfur Nucleophiles......Page 971
20.9 Hydrogen Nucleophiles......Page 972
Grignard Reagents......Page 973
Cyanohydrin Formation......Page 974
Wittig Reaction......Page 976
20.11 Baeyer-Villiger Oxidation of Aldehydes and Ketones......Page 980
Functional Group Interconversion......Page 981
Reactions Involving a Change in Carbon Skeleton......Page 982
IR Signals......Page 985
¹³C NMR Signals......Page 986
Review of Concepts and Vocabulary......Page 987
Key Terminology......Page 988
SkillBuilder Review......Page 989
Practice Problems......Page 991
Integrated Problems......Page 994
Challenge Problems......Page 995
21 Carboxylic Acids and Their Derivatives......Page 996
21.1 Introduction to Carboxylic Acids......Page 997
Diacids......Page 998
Acidity of Carboxylic Acids......Page 999
Carboxylic Acids at Physiological pH......Page 1001
Substituent Effects on Acidity......Page 1002
Carboxylation of Grignard Reagents......Page 1003
21.5 Reactions of Carboxylic Acids......Page 1004
Classes of Carboxylic Acid Derivatives......Page 1005
Naming Acid Halides......Page 1006
MEDICALLY SPEAKING: Sedatives......Page 1007
Naming Amides......Page 1008
Electrophilicity of Carboxylic Acid Derivatives......Page 1009
Nucleophilic Acyl Substitution......Page 1011
Preparation of Acid Chlorides......Page 1017
Hydrolysis of Acid Chlorides......Page 1018
Aminolysis of Acid Chlorides......Page 1019
Reduction of Acid Chlorides......Page 1020
Reactions between Acid Chlorides and Organometallic Reagents......Page 1021
Summary of Reactions of Acid Chlorides......Page 1022
Reactions of Acid Anhydrides......Page 1023
Acetylation with Acetic Anhydride......Page 1024
Preparation of Esters via SN2 Reactions......Page 1025
Preparation of Esters via Fischer Esterification......Page 1026
Saponification......Page 1027
PRACTICALLY SPEAKING: How Soap is Made......Page 1028
Reduction of Esters with Hydride-Reducing Agents......Page 1029
MEDICALLY SPEAKING: Esters as Prodrugs......Page 1030
Reactions between Esters and Grignard Reagents......Page 1031
Preparation of Amides......Page 1032
PRACTICALLY SPEAKING: Polyamides and Polyesters......Page 1033
Base-Catalyzed Hydrolysis of Amides......Page 1034
Reduction of Amides......Page 1035
MEDICALLY SPEAKING: Beta-Lactam Antibiotics......Page 1036
Hydrolysis of Nitriles......Page 1037
Reactions between Nitriles and Grignard Reagents......Page 1038
Functional Group Interconversions......Page 1039
C-C Bond-Forming Reactions......Page 1042
¹H NMR Spectroscopy......Page 1045
Review of Reactions......Page 1046
Review of Concepts and Vocabulary......Page 1047
SkillBuilder Review......Page 1049
Practice Problems......Page 1050
Integrated Problems......Page 1054
Challenge Problems......Page 1055
22 Alpha Carbon Chemistry: Enols and Enolates......Page 1056
Enols......Page 1057
Enolates......Page 1060
Choosing a Base for Enolate Formation......Page 1062
Alpha Halogenation in Acidic Conditions......Page 1064
Alpha Bromination of Carboxylic Acids: The Hell-Volhard-Zelinski Reaction......Page 1066
Alpha Halogenation in Basic Conditions: The Haloform Reaction......Page 1067
Aldol Additions......Page 1069
Aldol Condensations......Page 1071
PRACTICALLY SPEAKING: Muscle Power......Page 1072
PRACTICALLY SPEAKING: Why Meat from Younger Animals is Softer......Page 1076
Crossed Aldol Reactions......Page 1077
Intramolecular Aldol Reactions......Page 1079
The Claisen Condensation......Page 1080
Intramolecular Claisen Condensations: The Dieckmann Cyclization......Page 1082
Alkylation via Enolate Ions......Page 1083
The Malonic Ester Synthesis......Page 1085
The Acetoacetic Ester Synthesis......Page 1088
Michael Reactions......Page 1091
MEDICALLY SPEAKING: Glutathione Conjugation and Biological Michael Reactions......Page 1094
The Stork Enamine Synthesis......Page 1095
Reactions That Yield Difunctionalized Compounds......Page 1098
Alkylation of the Alpha and Beta Positions......Page 1100
Review of Reactions......Page 1103
Review of Concepts & Vocabulary......Page 1104
Key Terminology......Page 1105
SkillBuilder Review......Page 1106
Practice Problems......Page 1108
Integrated Problems......Page 1113
Challenge Problems......Page 1114
23 Amines......Page 1115
Classification of Amines......Page 1116
Reactivity of Amines......Page 1117
Nomenclature of Primary Amines......Page 1118
Colligative Properties......Page 1120
Other Distinctive Features of Amines......Page 1121
MEDICALLY SPEAKING: Fortunate Side Effects......Page 1122
Basicity of Amines......Page 1123
Delocalization Effects......Page 1124
Amines at Physiological pH......Page 1126
Preparing an Amine from a Carboxylic Acid......Page 1127
Alkylation of Ammonia......Page 1128
The Azide Synthesis......Page 1129
The Gabriel Synthesis......Page 1130
23.6 Preparation of Amines via Reductive Amination......Page 1132
23.7 Synthesis Strategies......Page 1134
23.8 Acylation of Amines......Page 1137
23.9 The Hofmann Elimination......Page 1138
23.10 Reactions of Amines with Nitrous Acid......Page 1141
Secondary Amines and Nitrous Acid......Page 1142
Primary Amines and Nitrous Acid......Page 1143
Sandmeyer Reactions......Page 1144
Other Substitution Reactions of Aryl diazonium Salts......Page 1145
Azo Coupling......Page 1146
Pyrrole and Imidazole......Page 1149
MEDICALLY SPEAKING: H2-Receptor Antagonists and the Development of Cimetidine......Page 1150
NMR Spectroscopy......Page 1152
Mass Spectrometry......Page 1153
Review of Reactions......Page 1154
Review of Concepts and Vocabulary......Page 1156
SkillBuilder Review......Page 1157
Practice Problems......Page 1159
Integrated Problems......Page 1163
Challenge Problems......Page 1164
24 Carbohydrates......Page 1165
Aldoses vs. Ketoses......Page 1166
D and L Sugars......Page 1167
Aldotetroses......Page 1169
Aldohexoses......Page 1170
24.4 Configuration of Ketoses......Page 1171
Cyclization of Hydroxyaldehydes......Page 1172
Pyranose Forms of Monosaccharides......Page 1174
Three-Dimensional Representations of Pyranose Rings......Page 1177
Furanose Forms of Monosaccharides......Page 1179
Ester and Ether Formation......Page 1180
MEDICALLY SPEAKING: Diseases Associated with Insufficient Glycoside Formation......Page 1182
Reduction of Monosaccharides......Page 1183
Oxidation of Monosaccharides......Page 1184
Chain Lengthening: the Kiliani-Fischer Synthesis......Page 1186
Chain Shortening: the Wohl Degradation......Page 1187
Maltose......Page 1188
MEDICALLY SPEAKING: Lactose Intolerance......Page 1191
PRACTICALLY SPEAKING: Artificial Sweeteners......Page 1192
Starch......Page 1193
24.9 Amino Sugars......Page 1194
24.10 N-Glycosides......Page 1195
MEDICALLY SPEAKING: Aminoglycoside Antibiotics......Page 1196
Review of Reactions......Page 1200
Key Terminology......Page 1201
SkillBuilder Review......Page 1202
Practice Problems......Page 1204
Challenge Problems......Page 1207
25 Amino Acids, Peptides, and Proteins......Page 1208
25.1 Introduction to Amino Acids, Peptides and Proteins......Page 1209
Naturally Occurring Amino Acids......Page 1210
Acid-Base Properties......Page 1212
Isoelectric Point......Page 1215
Separation of Amino Acids via Electrophoresis......Page 1216
Amino Acid Synthesis via α-Haloacids......Page 1217
Amino Acid Synthesis via the Amidomalonate Synthesis......Page 1218
Amino Acid Synthesis via the Strecker Synthesis......Page 1220
Enantioselective Synthesis of L Amino Acids......Page 1221
The Assembly of Peptides from Amino Acids......Page 1222
The Geometry of Peptide Bonds......Page 1225
Some Interesting Peptides......Page 1226
MEDICALLY SPEAKING: Polypeptide Antibiotics......Page 1228
The Edman degradation......Page 1229
Enzymatic Cleavage......Page 1230
Peptide Bond Formation......Page 1231
Protecting the Amino Group of an Amino Acid......Page 1233
Protecting the Carboxylic Acid Moiety of an Amino Acid......Page 1235
Preparing a Dipeptide......Page 1236
The Merrifield Synthesis......Page 1237
Primary Structure......Page 1240
Secondary Structure......Page 1241
Tertiary Structure......Page 1242
MEDICALLY SPEAKING: Diseases Caused by Misfolded Proteins......Page 1243
Structural Proteins......Page 1244
Review of Reactions......Page 1246
Key Terminology......Page 1248
SkillBuilder Review......Page 1249
Practice Problems......Page 1251
Challenge Problems......Page 1254
26 Lipids......Page 1255
26.1 Introduction to Lipids......Page 1256
26.2 Waxes......Page 1257
Properties of Fatty Acids and Triglycerides......Page 1258
Hydrogenation of Triglycerides......Page 1261
Autooxidation of Triglycerides......Page 1262
PRACTICALLY SPEAKING: Soaps vs. Synthetic Detergents......Page 1266
26.5 Phospholipids......Page 1270
Phosphoglycerides......Page 1271
Lipid Bilayers......Page 1272
MEDICALLY SPEAKING: Selectivity of Antifungal Agents......Page 1273
Introduction to Steroids......Page 1274
Biosynthesis of Cholesterol......Page 1275
Sex Hormones......Page 1277
MEDICALLY SPEAKING: Anabolic Steroids and Competitive Sports......Page 1279
26.7 Prostaglandins......Page 1280
MEDICALLY SPEAKING: NSAIDs and COX-2 Inhibitors......Page 1282
26.8 Terpenes......Page 1283
Classification of Terpenes......Page 1284
Review of Reactions: Synthetically Useful Reactions......Page 1288
Key Terminology......Page 1289
SkillBuilder Review......Page 1290
Practice Problems......Page 1291
Challenge Problems......Page 1293
27 Synthetic Polymers......Page 1294
27.2 Nomenclature of Synthetic Polymers......Page 1295
27.3 Copolymers......Page 1297
Addition Polymers......Page 1299
Condensation Polymers......Page 1304
Chain-Growth Polymers......Page 1307
Step-Growth Polymers......Page 1308
Branched Polymers......Page 1309
Linear Polymers......Page 1310
Cross-linked Polymers......Page 1311
27.7 Polymer Classification by Properties......Page 1312
Thermosetting Resins......Page 1313
PRACTICALLY SPEAKING: Safety Glass and Car Windshields......Page 1314
27.8 Polymer Recycling......Page 1315
Review of Reactions......Page 1316
Review of Concepts and Vocabulary......Page 1317
SkillBuilder Review......Page 1318
Practice Problems......Page 1319
Challenge Problems......Page 1321
Glossary......Page 1322
Credits......Page 1333
Index......Page 1335