March’s Advanced Organic Chemistry: Reactions, Mechanisms, and Structure	1
	Contents	7
	Preface	15
	Common Abbreviations	23
	Biographical Statement	27
	Part I: Introduction	29
	1. Localized Chemical Bonding	31
	1.A. Covalent Bonding	31
	1.B. Multiple Valence	34
	1.C. Hybridization	35
	1.D. Multiple Bonds	37
	1.E. Photoelectron Spectroscopy	39
	1.F. Electronic Structures of Molecules	42
	1.G. Electronegativity	43
	1.H. Dipole Moment	46
	1.I. Inductive and Field Effects	47
	1.J. Bond Distances	49
	1.K. Bond Angles	53
	1.L. Bond Energies	55
	2. Delocalized Chemical Bonding	59
	2.A. Molecular Orbitals	60
	2.B. Bond Energies and Distances in Compounds Containing Delocalized Bonds	63
	2.C. Molecules that have Delocalized Bonds	65
	2.D. Cross-Conjugation	70
	2.E. The Rules of Resonance	71
	2.F. The Resonance Effect	73
	2.G. Steric Inhibition of Resonance and the Influences of Strain	74
	2.H. p?–d? Bonding. Ylids	77
	2.I. Aromaticity	78
	2.I.i. Six-Membered Rings	82
	2.I.ii. Five, Seven, and Eight-Membered Rings	85
	2.I.iii. Other Systems Containing Aromatic Sextets	90
	2.J. Alternant and Nonalternant Hydrocarbons	91
	2.K. Aromatic Systems with Electron Numbers other than Six	93
	2.K.i. Systems of Two Electrons	94
	2.K.ii. Systems of Four Electrons: Antiaromaticity	95
	2.K.iii. Systems of Eight Electrons	99
	2.K.iv. Systems of Ten Electrons	100
	2.K.v. Systems of more than Ten Electrons: 4n + 2 Electrons	102
	2.K.vi. Systems of more than 10 Electrons: 4n Electrons	107
	2.L. Other Aromatic Compounds	110
	2.M. Hyperconjugation	113
	2.N. Tautomerism	117
	2.N.i. Keto–Enol Tautomerism	117
	2.N.ii. Other Proton-Shift Tautomerism	120
	3. Bonding Weaker Than Covalent	124
	3.A. Hydrogen Bonding	124
	3.B. ?–? Interactions	131
	3.C. Addition Compounds	132
	3.C.i. Electron Donor–Acceptor Complexes	132
	3.C.ii. Crown Ether Complexes and Cryptates	136
	3.C.iii. Inclusion Compounds	141
	3.C.iv. Cyclodextrins	144
	3.D. Catenanes and Rotaxanes	146
	3.E. Cucurbit[n]Uril-Based Gyroscane	149
	4. Stereochemistry and Conformation	150
	4.A. Optical Activity and Chirality	150
	4.A.i. Dependence of Rotation on Conditions of Measurement	152
	4.B. What Kinds of Molecules Display Optical Activity?	153
	4.C. The Fischer Projection	164
	4.D. Absolute Configuration	165
	4.D.i. The CAHN–INGOLD–PRELOG System	166
	4.D.ii. Methods of Determining Configuration	169
	4.E. The Cause of Optical Activity	173
	4.F. Molecules with more than One Stereogenic Center	174
	4.G. Asymmetric Synthesis	177
	4.H. Methods of Resolution	182
	4.I. Optical Purity	188
	4.J. cis–trans Isomerism	190
	4.J.i. cis-trans Isomerism Resulting from Double Bonds	190
	4.J.ii. cis–trans Isomerism of Monocyclic Compounds	193
	4.J.iii. cis–trans Isomerism of Fused and Bridged Ring Systems	195
	4.K. Out–In Isomerism	196
	4.L. Enantiotopic and Diastereotopic Atoms, Groups, and Faces	198
	4.M. Stereospecific and Stereoselective Syntheses	201
	4.N. Conformational Analysis	201
	4.N.i. Conformation in Open-Chain Systems	203
	4.N.ii. Conformation in Six-Membered Rings	208
	4.N.iii. Conformation in Six-Membered Rings Containing Heteroatoms	214
	4.N.iv. Conformation in Other Rings	216
	4.O. Molecular Mechanics	218
	4.P. STRAIN	220
	4.P.i. Strain in Small Rings	221
	4.P.ii. Strain in Other Rings	227
	4.P.iii. Unsaturated Rings	229
	4.P.iv. Strain Due to Unavoidable Crowding	232
	5. Carbocations, Carbanions, Free Radicals, Carbenes, and Nitrenes	236
	5.A. Carbocations	236
	5.A.i. Nomenclature	236
	5.A.ii. Stability and Structure of Carbocations	237
	5.A.iii. The Generation and Fate of Carbocations	246
	5.B. Carbanions	249
	5.B.i. Stability and Structure	249
	5.B.ii. The Structure of Organometallic Compounds	256
	5.B.iii. The Generation and Fate of Carbanions	261
	5.C. Free Radicals	262
	5.C.i. Stability and Structure	262
	5.C.ii. The Generation and Fate of Free Radicals	273
	5.C.iii. Radical Ions	276
	5.D. Carbenes	277
	5.D.i. Stability and Structure	277
	5.D.ii. The Generation and Fate of Carbenes	281
	5.E. Nitrenes	285
	6. Mechanisms and Methods of Determining them	289
	6.A. Types of Mechanism	289
	6.B. Types of Reaction	290
	6.C. Thermodynamic Requirements for Reaction	292
	6.D. Kinetic Requirements for Reaction	294
	6.E. The Baldwin Rules for Ring Closure	298
	6.F. Kinetic and Thermodynamic Control	299
	6.G. The Hammond Postulate	300
	6.H. Microscopic Reversibility	301
	6.I. Marcus Theory	301
	6.J. Methods of Determining Mechanisms	303
	6.J.i. Identification of Products	303
	6.J.ii. Determination of the Presence of an Intermediate	303
	6.J.iii. The Study of Catalysis	305
	6.J.iv. Isotopic Labeling	305
	6.J.v. Stereochemical Evidence	306
	6.J.vi. Kinetic Evidence	306
	6.J.vii. Isotope Effects	313
	7. Irradiation Processes in Organic Chemistry	317
	7.A. Photochemistry	317
	7.A.i. Excited States and the Ground State	317
	7.A.ii. Singlet and Triplet States: “Forbidden” Transitions	319
	7.A.iii. Types of Excitation	320
	7.A.iv. Nomenclature and Properties of Excited States	322
	7.A.v. Photolytic Cleavage	323
	7.A.vi. The Fate of the Excited Molecule: Physical Processes	324
	7.A.vii. The Fate of the Excited Molecule: Chemical Processes	329
	7.A.viii. The Determination of Photochemical Mechanisms	334
	7.B. Sonochemistry	335
	7.C. Microwave Chemistry	337
	8. Acids and Bases	340
	8.A. Brønsted Theory	340
	8.A.i. Brønsted Acids	341
	8.A.ii. Brønsted Bases	348
	8.B. The Mechanism of Proton-Transfer Reactions	351
	8.C. Measurements of Solvent Acidity	352
	8.D. Acid and Base Catalysis	355
	8.E. Lewis Acids and Bases	358
	8.E.i. Hard–Soft Acids–Bases	359
	8.F. The Effects of Structure on the Strengths of Acids and Bases	362
	8.G. The Effects of the Medium on Acid and Base Strength	371
	9. Effects of Structure and Medium on Reactivity	375
	9.A. Resonance and Field Effects	375
	9.B. Steric Effects	377
	9.C. Quantitative Treatments of the Effect of Structure on Reactivity	380
	9.D. Effect of Medium on Reactivity and Rate	389
	9.D.i. High Pressure	390
	9.D.ii. Water and Other Non-Organic Solvents	391
	9.D.iii. Ionic Solvents	392
	9.D.iv. Solventless Reactions	394
	Part II: Introduction	395
	10. Aliphatic Substitution, Nucleophilic and Organometallic	401
	10.A. Mechanisms	401
	10.A.i. The SN2 Mechanism	402
	10.A.ii. The SN1 Mechanism	407
	10.A.iii. Ion Pairs in the SN1 Mechanism	411
	10.A.iv. Mixed SN1 and SN2 Mechanisms	415
	10.B. SET Mechanisms	417
	10.C. The Neighboring-Group Mechanism	419
	10.C.i. Neighboring-Group Participation by ? and ? Bonds: Nonclassical Carbocations	422
	10.D. The SNi Mechanism	436
	10.E. Nucleophilic Substitution at an Allylic Carbon: Allylic Rearrangements	437
	10.F. Nucleophilic Substitution at an Aliphatic Trigonal Carbon: The Tetrahedral Mechanism	441
	10.G. Reactivity	445
	10.G.i. The Effect of Substrate Structure	445
	10.G.ii. The Effect of the Attacking Nucleophile	454
	10.G.iii. The Effect of the Leaving Group	460
	10.G.iv. The Effect of the Reaction Medium	463
	10.G.v. Phase-Transfer Catalysis	470
	10.G.vi. Influencing Reactivity by External Means	473
	10.G.vii. Ambident (Bidentant) Nucleophiles: Regioselectivity	474
	10.G.viii. Ambident Substrates	478
	10.H. Reactions	479
	10.H.i. Oxygen Nucleophiles	479
	10.H.ii. Attack by OR at an Alkyl Carbon	487
	10.H.iii. Sulfur Nucleophiles	503
	10.H.iv. Nitrogen Nucleophiles	509
	10.H.v. Halogen Nucleophiles	526
	10.H.vi. Carbon Nucleophiles	538
	11. Aromatic Substitution, Electrophilic	597
	11.A. Mechanisms	597
	11.A.i. The Arenium Ion Mechanism	598
	11.A.ii. The SE1 Mechanism	604
	11.B. Orientation and Reactivity	604
	11.B.i. Orientation and Reactivity in Monosubstituted Benzene Rings	604
	11.B.ii. The Ortho/Para Ratio	608
	11.B.iii. Ipso Attack	609
	11.B.iv. Orientation in Benzene Rings with More Than One Substituent	611
	11.B.v. Orientation in Other Ring Systems	612
	11.C. Quantitative Treatments of Reactivity in the Substrate	614
	11.D.A Quantitative Treatment of Reactivity of the Electrophile: The Selectivity Relationship	616
	11.E. The Effect of the Leaving Group	619
	11.F. Reactions	619
	11.F.i. Hydrogen as the Leaving Group in Simple Substitution Reactions	620
	11.F.ii. Hydrogen as the Leaving Group in Rearrangement Reactions	663
	11.F.iii. Other Leaving Groups	669
	12. Aliphatic, Alkenyl, and Alkynyl Substitution, Electrophilic and Organometallic	677
	12.A. Mechanisms	678
	12.A.i. Bimolecular Mechanisms: SE2 and SEi	678
	12.A.ii. The SE1 Mechanism	682
	12.A.iii. Electrophilic Substitution Accompanied by Double-Bond Shifts	685
	12.A.iv. Other Mechanisms	686
	12.B. Reactivity	686
	12.C. Reactions	688
	12.C.i. Hydrogen as Leaving Group	688
	12.C.ii. Metals as Leaving Groups	726
	12.C.iii. Halogen as Leaving Group	741
	12.C.iv. Carbon Leaving Groups	746
	12.C.v. Electrophilic Substitution at Nitrogen	755
	13. Aromatic Substitution: Nucleophilic and Organometallic	760
	13.A. Mechanisms	760
	13.A.i. The SNAr Mechanism	760
	13.A.ii. The SN1 Mechanism	763
	13.A.iii. The Benzyne Mechanism	765
	13.A.iv. The SRN1 Mechanism	767
	13.A.v. Other Mechanisms	768
	13.B. Reactivity	769
	13.B.i. The Effect of Substrate Structure	769
	13.B.ii. The Effect of the Leaving Group	772
	13.B.iii. The Effect of the Attacking Nucleophile	773
	13.C. Reactions	773
	13.C.i. All Leaving Groups Except Hydrogen and N2+	774
	13.C.ii. Hydrogen as Leaving Group	812
	13.C.iii. Nitrogen as Leaving Group	816
	13.C.iv. Rearrangements	825
	14. Substitution Reactions: Radical	831
	14.A. Mechanisms	831
	14.A.i. Radical Mechanisms in General	831
	14.A.ii. Free Radical Substitution Mechanisms	835
	14.A.iii. Mechanisms at an Aromatic Substrate	837
	14.A.iv. Neighboring-Group Assistance in Free Radical Reactions	838
	14.B. Reactivity	840
	14.B.i. Reactivity for Aliphatic Substrates	840
	14.B.ii. Reactivity at a Bridgehead	845
	14.B.iii. Reactivity in Aromatic Substrates	846
	14.B.iv. Reactivity in the Attacking Radical	847
	14.B.v. The Effect of Solvent on Reactivity	848
	14.C. Reactions	849
	14.C.i. Hydrogen as a Leaving Group	849
	14.C.ii. N2 as Leaving Group	874
	14.C.iii. Metals as Leaving Groups	877
	14.C.iv. Halogen as Leaving Group	879
	14.C.v. Sulfur as Leaving Group	879
	14.C.vi. Carbon as Leaving Group	881
	15. Addition to Carbon–Carbon Multiple Bonds	887
	15.A. Mechanisms	887
	15.A.i. Electrophilic Addition	887
	15.A.ii. Nucleophilic Addition	893
	15.A.iii. Free Radical Addition	895
	15.A.iv. Cyclic Mechanisms	897
	15.A.v. Addition to Conjugated Systems	897
	15.B. Orientation and Reactivity	899
	15.B.i. Reactivity	899
	15.B.ii. Orientation	902
	15.B.iii. Stereochemical Orientation	905
	15.B.iv. Addition to Cyclopropane Rings	907
	15.C. Reactions	909
	15.C.i. Isomerization of Double and Triple Bonds	909
	15.C.ii. Reactions in which Hydrogen Adds to One Side	911
	15.C.iii. Reactions in which Hydrogen Adds to Neither Side	1009
	15.C.iv. Cycloaddition Reactions	1042
	16. Addition to Carbon–Hetero Multiple Bonds	1095
	16.A. Mechanism and Reactivity	1095
	16.A.i. Nucleophilic Substitution at an Aliphatic Trigonal Carbon: The Tetrahedral Mechanism	1097
	16.B. Reactions	1103
	16.B.i. Reactions in which Hydrogen or a Metallic Ion Adds to the Heteroatom	1103
	16.B.ii. Acyl Substitution Reactions	1217
	16.B.iii. Reactions in which Carbon Adds to the Heteroatom	1267
	16.B.iv. Addition to Isocyanides	1274
	16.B.v. Nucleophilic Substitution at a Sulfonyl Sulfur Atom	1276
	17. Eliminations	1281
	17.A. Mechanisms and Orientation	1281
	17.A.i. The E2 Mechanism	1282
	17.A.ii. The E1 Mechanism	1289
	17.A.iii. The E1cB Mechanism	1290
	17.A.iv. The E1–E2–E1cB Spectrum	1295
	17.A.v. The E2C Mechanism	1296
	17.B. Regiochemistry of the Double Bond	1297
	17.C. Stereochemistry of the Double Bond	1301
	17.D. Reactivity	1302
	17.D.i. Effect of Substrate Structure	1302
	17.D.ii. Effect of the Attacking Base	1304
	17.D.iii. Effect of the Leaving Group	1304
	17.D.iv. Effect of the Medium	1305
	17.E. Mechanisms and Orientation in Pyrolytic Eliminations	1306
	17.E.i. Mechanisms	1306
	17.E.ii. Orientation in Pyrolytic Eliminations	1309
	17.E.iii. 1,4-Conjugate Eliminations	1310
	17.F. Reactions	1310
	17.F.i. Reactions in which C=C and C?C Bonds are Formed	1310
	17.F.ii. Fragmentations	1335
	17.F.iii. Reactions in which C?N or C=N Bonds are Formed	1338
	17.F.iv. Reactions in which C=O Bonds are Formed	1342
	17.F.v. Reactions in which N=N Bonds are Formed	1343
	17.F.vi. Extrusion Reactions	1344
	18. Rearrangements	1349
	18.A. Mechanisms	1350
	18.A.i. Nucleophilic Rearrangements	1350
	18.A.ii. The Actual Nature of the Migration	1352
	18.A.iii. Migratory Aptitudes	1356
	18.A.iv. Memory Effects	1358
	18.B. Longer Nucleophilic Rearrangements	1359
	18.C. Free Radical Rearrangements	1361
	18.D. Carbene Rearrangements	1365
	18.E. Electrophilic Rearrangements	1365
	18.F. Reactions	1365
	18.F.i. 1,2-Rearrangements	1366
	18.F.ii. Non-1,2 Rearrangements	1408
	19. Oxidations and Reductions	1461
	19.A. Mechanisms	1462
	19.B. Reactions	1464
	19.B.i. Oxidations	1465
	19.B.ii. Reductions	1525
	Appendix A: The Literature of Organic Chemistry	1597
	Appendix B: Classification of Reactions by Type of Compounds Synthesized	1633
	Indexes	1659
	Author Index	1659
	Subject Index	1863