Organic chemistry

Front Cover......Page 1
Title Page......Page 4
Copyright Page......Page 5
About the Author......Page 7
Contents in Brief......Page 8
Contents......Page 9
Preface......Page 21
Acknowledgments......Page 26
List of How To’s......Page 28
List of Mechanisms......Page 30
List of Selected Applications......Page 33
What Is Organic Chemistry?......Page 38
Some Representative Organic Molecules......Page 39
Ginkgolide B—A Complex Organic Compound from the Ginkgo Tree......Page 41
1 Structure and Bonding......Page 43
1.1 The Periodic Table......Page 44
1.2 Bonding......Page 47
1.3 Lewis Structures......Page 49
1.4 Lewis Structures Continued......Page 54
1.5 Resonance......Page 55
1.6 Determining Molecular Shape......Page 60
1.7 Drawing Organic Structures......Page 64
1.8 Hybridization......Page 69
1.9 Ethane, Ethylene, and Acetylene......Page 73
1.10 Bond Length and Bond Strength......Page 77
1.11 Electronegativity and Bond Polarity......Page 79
1.12 Polarity of Molecules......Page 81
1.13 L-Dopa—A Representative Organic Molecule......Page 82
Key Concepts......Page 83
Problems......Page 84
2 Acids and Bases......Page 91
2.1 Brønsted–Lowry Acids and Bases......Page 92
2.2 Reactions of Brønsted–Lowry Acids and Bases......Page 93
2.3 Acid Strength and pKa......Page 95
2.4 Predicting the Outcome of Acid–Base Reactions......Page 98
2.5 Factors That Determine Acid Strength......Page 99
2.6 Common Acids and Bases......Page 107
2.7 Aspirin......Page 108
2.8 Lewis Acids and Bases......Page 109
Key Concepts......Page 111
Problems......Page 112
3 Introduction to Organic Molecules and Functional Groups......Page 118
3.1 Functional Groups......Page 119
3.2 An Overview of Functional Groups......Page 120
3.3 Intermolecular Forces......Page 124
3.4 Physical Properties......Page 127
3.5 Application: Vitamins......Page 134
3.6 Application of Solubility: Soap......Page 135
3.7 Application: The Cell Membrane......Page 137
3.8 Functional Groups and Reactivity......Page 139
3.9 Biomolecules......Page 141
Key Concepts......Page 142
Problems......Page 143
4 Alkanes......Page 150
4.1 Alkanes—An Introduction......Page 151
4.2 Cycloalkanes......Page 155
4.3 An Introduction to Nomenclature......Page 156
4.4 Naming Alkanes......Page 157
4.5 Naming Cycloalkanes......Page 162
4.6 Common Names......Page 164
4.7 Fossil Fuels......Page 165
4.9 Conformations of Acyclic Alkanes—Ethane......Page 166
4.10 Conformations of Butane......Page 171
4.11 An Introduction to Cycloalkanes......Page 174
4.12 Cyclohexane......Page 175
4.13 Substituted Cycloalkanes......Page 178
4.14 Oxidation of Alkanes......Page 184
4.15 Lipids—Part 1......Page 186
Key Concepts......Page 188
Problems......Page 190
5 Stereochemistry......Page 196
5.1 Starch and Cellulose......Page 197
5.2 The Two Major Classes of Isomers......Page 199
5.3 Looking Glass Chemistry—Chiral and Achiral Molecules......Page 200
5.4 Stereogenic Centers......Page 203
5.5 Stereogenic Centers in Cyclic Compounds......Page 205
5.6 Labeling Stereogenic Centers with R or S......Page 207
5.7 Diastereomers......Page 212
5.8 Meso Compounds......Page 214
5.9 R and S Assignments in Compounds with Two or More Stereogenic Centers......Page 216
5.10 Disubstituted Cycloalkanes......Page 217
5.11 Isomers—A Summary......Page 218
5.12 Physical Properties of Stereoisomers......Page 219
5.13 Chemical Properties of Enantiomers......Page 223
Key Concepts......Page 225
Problems......Page 227
6 Understanding Organic Reactions......Page 233
6.1 Writing Equations for Organic Reactions......Page 234
6.2 Kinds of Organic Reactions......Page 235
6.3 Bond Breaking and Bond Making......Page 237
6.4 Bond Dissociation Energy......Page 240
6.5 Thermodynamics......Page 243
6.6 Enthalpy and Entropy......Page 246
6.7 Energy Diagrams......Page 247
6.8 Energy Diagram for a Two-Step Reaction Mechanism......Page 250
6.9 Kinetics......Page 252
6.10 Catalysts......Page 255
6.11 Enzymes......Page 256
Key Concepts......Page 257
Problems......Page 259
7 Alkyl Halides and Nucleophilic Substitution......Page 265
7.1 Introduction to Alkyl Halides......Page 266
7.2 Nomenclature......Page 267
7.3 Physical Properties......Page 268
7.4 Interesting Alkyl Halides......Page 269
7.5 The Polar Carbon–Halogen Bond......Page 271
7.6 General Features of Nucleophilic Substitution......Page 272
7.7 The Leaving Group......Page 273
7.8 The Nucleophile......Page 275
7.9 Possible Mechanisms for Nucleophilic Substitution......Page 279
7.10 Two Mechanisms for Nucleophilic Substitution......Page 280
7.11 The S[sub(N)]2 Mechanism......Page 281
7.12 Application: Useful S[sub(N)]2 Reactions......Page 287
7.13 The SN1 Mechanism......Page 289
7.14 Carbocation Stability......Page 293
7.15 The Hammond Postulate......Page 295
7.16 Application: SN1 Reactions, Nitrosamines, and Cancer......Page 298
7.17 When Is the Mechanism SN1 or SN2?......Page 299
7.19 Organic Synthesis......Page 304
Key Concepts......Page 307
Problems......Page 308
8 Alkyl Halides and Elimination Reactions......Page 315
8.1 General Features of Elimination......Page 316
8.2 Alkenes—The Products of Elimination Reactions......Page 318
8.4 The E2 Mechanism......Page 322
8.5 The Zaitsev Rule......Page 325
8.6 The E1 Mechanism......Page 328
8.7 S[sub(N)]1 and E1 Reactions......Page 331
8.8 Stereochemistry of the E2 Reaction......Page 332
8.9 When Is the Mechanism E1 or E2?......Page 335
8.10 E2 Reactions and Alkyne Synthesis......Page 336
8.11 When Is the Reaction S[sub(N)]1, S[sub(N)]2, E1, or E2?......Page 337
Key Concepts......Page 341
Problems......Page 342
9 Alcohols, Ethers, and Epoxides......Page 349
9.1 Introduction......Page 350
9.3 Nomenclature......Page 351
9.4 Physical Properties......Page 355
9.5 Interesting Alcohols, Ethers, and Epoxides......Page 356
9.6 Preparation of Alcohols, Ethers, and Epoxides......Page 358
9.7 General Features—Reactions of Alcohols, Ethers, and Epoxides......Page 360
9.8 Dehydration of Alcohols to Alkenes......Page 361
9.9 Carbocation Rearrangements......Page 365
9.10 Dehydration Using POCl[sub(3)] and Pyridine......Page 367
9.11 Conversion of Alcohols to Alkyl Halides with HX......Page 368
9.12 Conversion of Alcohols to Alkyl Halides with SOCl2 and PBr3......Page 372
9.13 Tosylate—Another Good Leaving Group......Page 375
9.14 Reaction of Ethers with Strong Acid......Page 378
9.15 Reactions of Epoxides......Page 380
9.16 Application: Epoxides, Leukotrienes, and Asthma......Page 384
Key Concepts......Page 386
Problems......Page 388
10 Alkenes......Page 395
10.1 Introduction......Page 396
10.2 Calculating Degrees of Unsaturation......Page 397
10.3 Nomenclature......Page 399
10.4 Physical Properties......Page 402
10.6 Lipids—Part 2......Page 403
10.7 Preparation of Alkenes......Page 406
10.8 Introduction to Addition Reactions......Page 407
10.9 Hydrohalogenation—Electrophilic Addition of HX......Page 408
10.10 Markovnikov’s Rule......Page 411
10.11 Stereochemistry of Electrophilic Addition of HX......Page 413
10.12 Hydration—Electrophilic Addition of Water......Page 415
10.13 Halogenation—Addition of Halogen......Page 416
10.14 Stereochemistry of Halogenation......Page 418
10.15 Halohydrin Formation......Page 420
10.16 Hydroboration–Oxidation......Page 422
10.17 Keeping Track of Reactions......Page 427
10.18 Alkenes in Organic Synthesis......Page 428
Key Concepts......Page 430
Problems......Page 431
11 Alkynes......Page 436
11.1 Introduction......Page 437
11.2 Nomenclature......Page 438
11.4 Interesting Alkynes......Page 439
11.5 Preparation of Alkynes......Page 441
11.6 Introduction to Alkyne Reactions......Page 442
11.7 Addition of Hydrogen Halides......Page 443
11.9 Addition of Water......Page 446
11.10 Hydroboration–Oxidation......Page 449
11.11 Reaction of Acetylide Anions......Page 451
11.12 Synthesis......Page 454
Key Concepts......Page 456
Problems......Page 458
12 Oxidation and Reduction......Page 463
12.1 Introduction......Page 464
12.3 Reduction of Alkenes......Page 465
12.4 Application: Hydrogenation of Oils......Page 469
12.5 Reduction of Alkynes......Page 471
12.6 The Reduction of Polar C–X σ Bonds......Page 474
12.7 Oxidizing Agents......Page 475
12.8 Epoxidation......Page 476
12.9 Dihydroxylation......Page 479
12.10 Oxidative Cleavage of Alkenes......Page 481
12.11 Oxidative Cleavage of Alkynes......Page 483
12.12 Oxidation of Alcohols......Page 484
12.13 Green Chemistry......Page 487
12.15 Sharpless Epoxidation......Page 488
Key Concepts......Page 491
Problems......Page 494
13 Mass Spectrometry and Infrared Spectroscopy......Page 500
13.1 Mass Spectrometry......Page 501
13.2 Alkyl Halides and the M + 2 Peak......Page 505
13.3 Fragmentation......Page 506
13.4 Other Types of Mass Spectrometry......Page 509
13.5 Electromagnetic Radiation......Page 511
13.6 Infrared Spectroscopy......Page 513
13.7 IR Absorptions......Page 515
13.8 IR and Structure Determination......Page 522
Key Concepts......Page 524
Problems......Page 525
14 Nuclear Magnetic Resonance Spectroscopy......Page 531
14.1 An Introduction to NMR Spectroscopy......Page 532
14.2 [sup(1)]H NMR: Number of Signals......Page 535
14.3 [sup(1)]H NMR: Position of Signals......Page 539
14.4 The Chemical Shift of Protons on sp[sup(2)] and sp Hybridized Carbons......Page 542
14.5 [sup(1)]H NMR: Intensity of Signals......Page 544
14.6 [sup(1)]H NMR: Spin–Spin Splitting......Page 545
14.7 More Complex Examples of Splitting......Page 550
14.8 Spin–Spin Splitting in Alkenes......Page 553
14.9 Other Facts About [sup(1)]H NMR Spectroscopy......Page 554
14.10 Using [sup(1)]H NMR to Identify an Unknown......Page 556
14.11 [sup(13)]C NMR Spectroscopy......Page 559
Key Concepts......Page 564
Problems......Page 565
15 Radical Reactions......Page 575
15.1 Introduction......Page 576
15.2 General Features of Radical Reactions......Page 577
15.3 Halogenation of Alkanes......Page 578
15.4 The Mechanism of Halogenation......Page 579
15.5 Chlorination of Other Alkanes......Page 582
15.6 Chlorination versus Bromination......Page 583
15.7 Halogenation as a Tool in Organic Synthesis......Page 585
15.8 The Stereochemistry of Halogenation Reactions......Page 586
15.9 Application: The Ozone Layer and CFCs......Page 588
15.10 Radical Halogenation at an Allylic Carbon......Page 589
15.11 Application: Oxidation of Unsaturated Lipids......Page 593
15.12 Application: Antioxidants......Page 594
15.13 Radical Addition Reactions to Double Bonds......Page 595
15.14 Polymers and Polymerization......Page 597
Key Concepts......Page 600
Problems......Page 601
16 Conjugation, Resonance, and Dienes......Page 608
16.1 Conjugation......Page 609
16.2 Resonance and Allylic Carbocations......Page 611
16.3 Common Examples of Resonance......Page 612
16.4 The Resonance Hybrid......Page 614
16.5 Electron Delocalization, Hybridization, and Geometry......Page 615
16.6 Conjugated Dienes......Page 617
16.8 The Carbon–Carbon σ Bond Length in 1,3-Butadiene......Page 618
16.9 Stability of Conjugated Dienes......Page 620
16.10 Electrophilic Addition: 1,2- Versus 1,4-Addition......Page 621
16.11 Kinetic Versus Thermodynamic Products......Page 623
16.12 The Diels–Alder Reaction......Page 625
16.13 Specific Rules Governing the Diels–Alder Reaction......Page 627
16.14 Other Facts About the Diels–Alder Reaction......Page 632
16.15 Conjugated Dienes and Ultraviolet Light......Page 634
Key Concepts......Page 636
Problems......Page 638
17 Benzene and Aromatic Compounds......Page 644
17.1 Background......Page 645
17.2 The Structure of Benzene......Page 646
17.3 Nomenclature of Benzene Derivatives......Page 647
17.4 Spectroscopic Properties......Page 650
17.5 Interesting Aromatic Compounds......Page 651
17.6 Benzene’s Unusual Stability......Page 652
17.7 The Criteria for Aromaticity—Hückel’s Rule......Page 654
17.8 Examples of Aromatic Compounds......Page 657
17.9 What Is the Basis of Hückel’s Rule?......Page 663
17.10 The Inscribed Polygon Method for Predicting Aromaticity......Page 666
17.11 Buckminsterfullerene—Is It Aromatic?......Page 669
Problems......Page 670
18 Electrophilic Aromatic Substitution......Page 678
18.2 The General Mechanism......Page 679
18.3 Halogenation......Page 681
18.4 Nitration and Sulfonation......Page 683
18.5 Friedel–Crafts Alkylation and Friedel–Crafts Acylation......Page 684
18.6 Substituted Benzenes......Page 691
18.7 Electrophilic Aromatic Substitution of Substituted Benzenes......Page 694
18.8 Why Substituents Activate or Deactivate a Benzene Ring......Page 696
18.9 Orientation Effects in Substituted Benzenes......Page 698
18.10 Limitations on Electrophilic Substitution Reactions with Substituted Benzenes......Page 702
18.11 Disubstituted Benzenes......Page 703
18.12 Synthesis of Benzene Derivatives......Page 705
18.13 Halogenation of Alkyl Benzenes......Page 706
18.14 Oxidation and Reduction of Substituted Benzenes......Page 708
18.15 Multistep Synthesis......Page 712
Key Concepts......Page 715
Problems......Page 717
19 Carboxylic Acids and the Acidity of the O–H Bond......Page 725
19.1 Structure and Bonding......Page 726
19.2 Nomenclature......Page 727
19.3 Physical Properties......Page 729
19.4 Spectroscopic Properties......Page 730
19.5 Interesting Carboxylic Acids......Page 731
19.6 Aspirin, Arachidonic Acid, and Prostaglandins......Page 733
19.7 Preparation of Carboxylic Acids......Page 734
19.8 Reactions of Carboxylic Acids—General Features......Page 736
19.9 Carboxylic Acids—Strong Organic Brønsted–Lowry Acids......Page 737
19.10 Inductive Effects in Aliphatic Carboxylic Acids......Page 740
19.11 Substituted Benzoic Acids......Page 742
19.12 Extraction......Page 744
19.13 Sulfonic Acids......Page 746
19.14 Amino Acids......Page 747
Key Concepts......Page 750
Problems......Page 751
20 Introduction to Carbonyl Chemistry; Organometallic Reagents; Oxidation and Reduction......Page 758
20.1 Introduction......Page 759
20.2 General Reactions of Carbonyl Compounds......Page 760
20.3 A Preview of Oxidation and Reduction......Page 763
20.4 Reduction of Aldehydes and Ketones......Page 764
20.5 The Stereochemistry of Carbonyl Reduction......Page 766
20.6 Enantioselective Carbonyl Reductions......Page 768
20.7 Reduction of Carboxylic Acids and Their Derivatives......Page 770
20.8 Oxidation of Aldehydes......Page 775
20.9 Organometallic Reagents......Page 776
20.10 Reaction of Organometallic Reagents with Aldehydes and Ketones......Page 779
20.11 Retrosynthetic Analysis of Grignard Products......Page 783
20.12 Protecting Groups......Page 785
20.13 Reaction of Organometallic Reagents with Carboxylic Acid Derivatives......Page 787
20.14 Reaction of Organometallic Reagents with Other Compounds......Page 790
20.15 α,β-Unsaturated Carbonyl Compounds......Page 792
20.16 Summary—The Reactions of Organometallic Reagents......Page 795
20.17 Synthesis......Page 796
Key Concepts......Page 799
Problems......Page 802
21 Aldehydes and Ketones—Nucleophilic Addition......Page 811
21.1 Introduction......Page 812
21.2 Nomenclature......Page 813
21.3 Physical Properties......Page 816
21.4 Spectroscopic Properties......Page 817
21.5 Interesting Aldehydes and Ketones......Page 820
21.6 Preparation of Aldehydes and Ketones......Page 821
21.7 Reactions of Aldehydes and Ketones—General Considerations......Page 822
21.8 Nucleophilic Addition of H– and R–—A Review......Page 826
21.9 Nucleophilic Addition of –CN......Page 827
21.10 The Wittig Reaction......Page 829
21.11 Addition of 1° Amines......Page 834
21.12 Addition of 2° Amines......Page 837
21.13 Addition of H2O—Hydration......Page 839
21.14 Addition of Alcohols—Acetal Formation......Page 841
21.15 Acetals as Protecting Groups......Page 845
21.16 Cyclic Hemiacetals......Page 846
21.17 An Introduction to Carbohydrates......Page 849
Key Concepts......Page 850
Problems......Page 852
22 Carboxylic Acids and Their Derivatives— Nucleophilic Acyl Substitution......Page 862
22.1 Introduction......Page 863
22.2 Structure and Bonding......Page 865
22.3 Nomenclature......Page 867
22.4 Physical Properties......Page 871
22.5 Spectroscopic Properties......Page 872
22.6 Interesting Esters and Amides......Page 873
22.7 Introduction to Nucleophilic Acyl Substitution......Page 875
22.8 Reactions of Acid Chlorides......Page 879
22.9 Reactions of Anhydrides......Page 881
22.10 Reactions of Carboxylic Acids......Page 882
22.11 Reactions of Esters......Page 887
22.12 Application: Lipid Hydrolysis......Page 890
22.13 Reactions of Amides......Page 892
22.14 Application: The Mechanism of Action of β-Lactam Antibiotics......Page 893
22.15 Summary of Nucleophilic Acyl Substitution Reactions......Page 894
22.16 Natural and Synthetic Fibers......Page 895
22.17 Biological Acylation Reactions......Page 897
22.18 Nitriles......Page 899
Key Concepts......Page 904
Problems......Page 907
23 Substitution Reactions of Carbonyl Compounds at the ` Carbon......Page 917
23.2 Enols......Page 918
23.3 Enolates......Page 921
23.4 Enolates of Unsymmetrical Carbonyl Compounds......Page 926
23.5 Racemization at the α Carbon......Page 928
23.7 Halogenation at the α Carbon......Page 929
23.8 Direct Enolate Alkylation......Page 934
23.9 Malonic Ester Synthesis......Page 937
23.10 Acetoacetic Ester Synthesis......Page 940
Key Concepts......Page 943
Problems......Page 945
24 Carbonyl Condensation Reactions......Page 953
24.1 The Aldol Reaction......Page 954
24.2 Crossed Aldol Reactions......Page 958
24.3 Directed Aldol Reactions......Page 962
24.4 Intramolecular Aldol Reactions......Page 963
24.5 The Claisen Reaction......Page 965
24.6 The Crossed Claisen and Related Reactions......Page 967
24.7 The Dieckmann Reaction......Page 969
24.8 The Michael Reaction......Page 971
24.9 The Robinson Annulation......Page 973
Key Concepts......Page 977
Problems......Page 978
25 Amines......Page 986
25.2 Structure and Bonding......Page 987
25.3 Nomenclature......Page 989
25.4 Physical Properties......Page 991
25.5 Spectroscopic Properties......Page 992
25.6 Interesting and Useful Amines......Page 993
25.7 Preparation of Amines......Page 997
25.9 Amines as Bases......Page 1003
25.10 Relative Basicity of Amines and Other Compounds......Page 1005
25.11 Amines as Nucleophiles......Page 1012
25.12 Hofmann Elimination......Page 1014
25.13 Reaction of Amines with Nitrous Acid......Page 1017
25.14 Substitution Reactions of Aryl Diazonium Salts......Page 1019
25.15 Coupling Reactions of Aryl Diazonium Salts......Page 1023
25.16 Application: Synthetic Dyes......Page 1025
25.17 Application: Sulfa Drugs......Page 1027
Key Concepts......Page 1028
Problems......Page 1031
26 Carbon–Carbon Bond-Forming Reactions in Organic Synthesis......Page 1039
26.1 Coupling Reactions of Organocuprate Reagents......Page 1040
26.2 Suzuki Reaction......Page 1042
26.3 Heck Reaction......Page 1046
26.4 Carbenes and Cyclopropane Synthesis......Page 1049
26.5 Simmons–Smith Reaction......Page 1051
26.6 Metathesis......Page 1052
Key Concepts......Page 1057
Problems......Page 1058
27 Carbohydrates......Page 1064
27.2 Monosaccharides......Page 1065
27.3 The Family of D-Aldoses......Page 1071
27.4 The Family of D-Ketoses......Page 1072
27.6 The Cyclic Forms of Monosaccharides......Page 1073
27.7 Glycosides......Page 1079
27.8 Reactions of Monosaccharides at the OH Groups......Page 1083
27.9 Reactions at the Carbonyl Group—Oxidation and Reduction......Page 1084
27.10 Reactions at the Carbonyl Group—Adding or Removing One Carbon Atom......Page 1086
27.11 The Fischer Proof of the Structure of Glucose......Page 1090
27.12 Disaccharides......Page 1093
27.13 Polysaccharides......Page 1096
27.14 Other Important Sugars and Their Derivatives......Page 1098
Key Concepts......Page 1103
Problems......Page 1105
28 Amino Acids and Proteins......Page 1111
28.1 Amino Acids......Page 1112
28.2 Synthesis of Amino Acids......Page 1115
28.3 Separation of Amino Acids......Page 1118
28.4 Enantioselective Synthesis of Amino Acids......Page 1122
28.5 Peptides......Page 1123
28.6 Peptide Sequencing......Page 1127
28.7 Peptide Synthesis......Page 1131
28.8 Automated Peptide Synthesis......Page 1136
28.9 Protein Structure......Page 1138
28.10 Important Proteins......Page 1143
Key Concepts......Page 1148
Problems......Page 1150
29 Lipids......Page 1156
29.1 Introduction......Page 1157
29.2 Waxes......Page 1158
29.3 Triacylglycerols......Page 1159
29.4 Phospholipids......Page 1163
29.5 Fat-Soluble Vitamins......Page 1165
29.6 Eicosanoids......Page 1166
29.7 Terpenes......Page 1169
29.8 Steroids......Page 1175
Key Concepts......Page 1180
Problems......Page 1181
30 Synthetic Polymers......Page 1185
30.1 Introduction......Page 1186
30.2 Chain-Growth Polymers—Addition Polymers......Page 1187
30.3 Anionic Polymerization of Epoxides......Page 1193
30.4 Ziegler–Natta Catalysts and Polymer Stereochemistry......Page 1194
30.5 Natural and Synthetic Rubbers......Page 1196
30.6 Step-Growth Polymers—Condensation Polymers......Page 1197
30.7 Polymer Structure and Properties......Page 1201
30.8 Green Polymer Synthesis......Page 1203
30.9 Polymer Recycling and Disposal......Page 1206
Key Concepts......Page 1209
Problems......Page 1210
Appendix A: pKa Values for Selected Compounds......Page 1217
Appendix B: Nomenclature......Page 1219
Appendix C: Bond Dissociation Energies for Some Common Bonds......Page 1223
Appendix D: Reactions that Form Carbon–Carbon Bonds......Page 1225
Appendix E: Characteristic IR Absorption Frequencies......Page 1226
Appendix F: Characteristic NMR Absorptions......Page 1227
Appendix G: General Types of Organic Reactions......Page 1229
Appendix H: How to Synthesize Particular Functional Groups......Page 1231
Glossary......Page 1235
Credits......Page 1253
Index......Page 1255