March's Advanced Organic Chemistry

Michael B. Smith, PhD, is Professor Emeritus in the Department of Chemistry at the University of Connecticut. He is a coauthor of the fifth through eighth editions of March’s Advanced Organic Chemistry and the author of Volumes 6 - 13 of the Compendium of Organic Synthetic Methods, as well as several other monographs and textbooks.

• New Reaction Sections Correlation: 8th Edition → 9th Editions xiiiPreface xixCommon Abbreviations xxiBiographical Statement xxviiNew Features of the 9th Edition xxixPart I Introduction 11. Localized Chemical Bonding 31.a. Covalent Bonding 31.b. Multiple Valence 61.c. Hybridization 61.d. Multiple Bonds 71.e. Photoelectron Spectroscopy 91.f. Electronic Structures of Molecules 111.g. Electronegativity 131.h. Dipole Moment 151.i. Inductive and Field Effects 161.j. Bond Distances 191.k. Bond Angles 221.l. Bond Energies 232. Delocalized Chemical Bonding 272.a. Molecular Orbitals 282.b. Bond Energies and Distances in Compounds Containing Delocalized Bonds 312.c. Molecules that have Delocalized Bonds 322.d. Cross- Conjugation 352.e. The Rules of Resonance 362.f. The Resonance Effect 372.g. Steric Inhibition of Resonance and the Influences of Strain 372.h. pπ–dπ Bonding. Ylids 402.i. Aromaticity 422.I.i. Six- Membered Rings 452.I.ii. Five- , Seven- , and Eight- Membered Rings 482.I.iii. Other Systems Containing Aromatic Sextets 522.j. Alternant and Nonalternant Hydrocarbons 542.k. Aromatic Systems with Electron Numbers other than Six 542.K.i. Systems of Two Electrons 552.K.ii. Systems of Four Electrons: Antiaromaticity 562.K.iii. Systems of Eight Electrons 592.K.iv. Systems of Ten Electrons 602.K.v. Systems of More than Ten Electrons: 4n + 2 Electrons 622.K.vi. Systems of More than Ten Electrons: 4n Electrons 662.l. Other Aromatic Compounds 702.M. Hyperconjugation 722.n. Tautomerism 752.N.i. Keto- Enol Tautomerism 752.N.ii. Other Proton- Shift Tautomerism 793. Bonding Weaker Than Covalent 833.a. Hydrogen Bonding 833.b. π–π Interactions 903.c. Addition Compounds 913.C.i. Electron Donor–Acceptor Complexes 923.C.ii. Crown Ether Complexes and Cryptates 943.C.iii. Inclusion Compounds 993.C.iv. Cyclodextrins 1023.d. Catenanes and Rotaxanes 1043.e. Cucurbit[n]Uril- Based Gyroscane 1074. Stereochemistry and Conformation 1094.a. Optical Activity and Chirality 1094.b. Dependence of Rotation on Conditions of Measurement 1114.c. What kinds of Molecules Display Optical Activity? 1124.d. The Fischer Projection 1214.e. Absolute Configuration 1214.E.i. The Cahn–Ingold–Prelog System 1224.E.ii. Methods of Determining Configuration 1254.f. Optical Purity 1284.g. The Cause of Optical Activity 1304.h. Molecules with more than One Stereogenic Center 1314.i. Asymmetric Synthesis 1344.j. Methods of Resolution 1374.k. Cis–Trans Isomerism 1424.K.i. Cis–Trans Isomerism Resulting from Double Bonds 1424.K.ii. Cis–Trans Isomerism of Monocyclic Compounds 1454.K.iii. Cis–Trans Isomerism of Fused and Bridged Ring Systems 1464.l. Out–In Isomerism 1474.M. Enantiotopic and Diastereotopic Atoms, Groups, and Faces 1494.n. Stereospecific and Stereoselective Syntheses 1514.o. Conformational Analysis 1524.O.i. Conformation in Open- Chain Systems 1534.O.ii. Conformation in Six- Membered Rings 1584.O.iii. Conformation in Six- Membered Rings Containing Heteroatoms 1624.O.iv. Conformation in Other Rings 1644.p. Molecular Mechanics 1664.q. Strain 1684.Q.i. Strain in Small Rings 1684.Q.ii. Strain in Other Rings 1724.Q.iii. Unsaturated Rings 1744.Q.iv. Strain Due to Unavoidable Crowding 1775. Carbocations, Carbanions, Free Radicals, Carbenes, and Nitrenes 1815.a. Carbocations 1825.A.i. Nomenclature 1825.A.ii. Stability and Structure of Carbocations 1825.A.iii. The Generation and Fate of Carbocations 1905.b. Carbanions 1925.B.i. Stability and Structure 1925.B.ii. The Structure of Grignard Reagents and Organolithium Reagents 1985.B.iii. The Generation and Fate of Carbanions 2015.c. Free Radicals 2025.C.i. Stability and Structure 2025.C.ii. The Generation and Fate of Free Radicals 2125.C.iii. Radical Ions 2155.d. Carbenes 2175.D.i. Stability and Structure 2175.D.ii. The Generation and Fate of Carbenes 2205.D.iii. N- Heterocyclic Carbenes 2235.e. Nitrenes 2256. Mechanisms and Methods of Determining Them 2296.a. Types of Mechanism 2296.b. Types of Reaction 2306.c. Thermodynamic Requirements for Reaction 2326.d. Kinetic Requirements for Reaction 2336.e. The Baldwin Rules for Ring Closure 2366.f. Kinetic and Thermodynamic Control 2386.g. The Hammond Postulate 2386.h. Microscopic Reversibility 2396.i. Marcus Theory 2396.j. Methods of Determining Mechanisms 2406.J.i. Identification of Products 2416.J.ii. Determination of the Presence of an Intermediate 2416.J.iii. The Study of Catalysis 2426.J.iv. Isotopic Labeling 2436.J.v. Stereochemical Evidence 2436.J.vi. Kinetic Evidence 2446.J.vii. Isotope Effects 2506.k. Catalyst Development 2537. Irradiation Processes and Techniques that Influence Reactions in Organic Chemistry 2577.a. Photochemistry 2577.A.i. Excited States and the Ground State 2577.A.ii. Singlet and Triplet States: “Forbidden” Transitions 2597.A.iii. Types of Excitation 2607.A.iv. Nomenclature and Properties of Excited States 2627.A.v. Photolytic Cleavage 2627.A.vi. The Fate of the Excited Molecule: Physical Processes 2637.A.vii. The Fate of the Excited Molecule: Chemical Processes 2677.A.viii. The Determination of Photochemical Mechanisms 2717.b. Sonochemistry 2727.c. Microwave Chemistry 2747.d. Flow Chemistry 2757.e. Mechanochemistry 2768. Acids and Bases 2798.a. Brønsted Theory 2798.A.i. Brønsted Acids 2808.A.ii. Brønsted Bases 2868.b. The Mechanism of Proton Transfer Reactions 2898.c. Measurements of Solvent Acidity 2908.d. Acid and Base Catalysis 2938.e. Lewis Acids and Bases 2958.E.i. Hard–Soft Acids–Bases 2968.f. The Effects of Structure on the Strengths of Acids and Bases 2988.g. The Effects of the Medium on Acid and Base Strength 3069. Effects of Structure and Medium on Reactivity 3099.a. Resonance and Field Effects 3099.b. Steric Effects 3119.c. Quantitative Treatments of the Effect of Structure on Reactivity 3139.d. Effect of Medium on Reactivity and Rate 3209.e. High Pressure 3219.f. Water and other Nonorganic Solvents 3219.g. Ionic Liquid Solvents 3239.h. Solventless Reactions 325Part II Introduction 32710. Aliphatic Substitution: Nucleophilic and Organometallic 32910.A. Mechanisms 33010.A.i. The S N 2 Mechanism 33010.A.ii. The S N 1 Mechanism 33410.A.iii. Ion Pairs in the S N 1 Mechanism 33810.A.iv. Mixed S N 1 and S N 2 Mechanisms 34010.B. Set Mechanisms 34210.C. The Neighboring- Group Mechanism 34410.C.i. Neighboring- Group Participation by π and σ Bonds: Nonclassical Carbocations 34710.D. The S N I Mechanism 35910.E. Nucleophilic Substitution at an Allylic Carbon: Allylic Rearrangements 36010.F. Nucleophilic Substitution at an Aliphatic Trigonal Carbon: The Tetrahedral Mechanism 36310.G. Reactivity 36610.G.i. The Effect of Substrate Structure 36610.G.ii. The Effect of the Attacking Nucleophile 37410.G.iii. The Effect of the Leaving Group 37810.G.iv. The Effect of the Reaction Medium 38210.G.v. Phase- Transfer Catalysis 38710.G.vi. Influencing Reactivity by External Means 38910.G.vii. Ambident (Bidentant) Nucleophiles: Regioselectivity 39010.G.viii. Ambident Substrates 39310.H. Reactions 39411. Aromatic Substitution: Electrophilic 49111.A. Mechanisms 49111.A.i. The Arenium Ion Mechanism 49111.B. Orientation and Reactivity 49611.B.i. Orientation and Reactivity in Monosubstituted Benzene Rings 49611.B.ii. The Ortho/Para Ratio 49911.B.iii. Ipso Attack 50011.B.iv. Orientation in Benzene Rings with more than one Substituent 50111.B.v. Orientation in Other Ring Systems 50211.C. Quantitative Treatments of Reactivity in the Substrate 50411.D. A Quantitative Treatment of Reactivity of the Electrophile: The Selectivity Relationship 50511.E. The Effect of the Leaving Group 50711.F. Reactions 50712. Aliphatic, Alkenyl, and Alkynyl Substitution: Electrophilic and Organometallic 55512.A. Mechanisms 55512.A.i. Bimolecular Mechanisms: S E 2 and S E I 55612.A.ii. The S E 1 Mechanism 55812.A.iii. Electrophilic Substitution Accompanied by Double- Bond Shifts 56012.A.iv. Other Mechanisms 56112.B. Reactivity 56112.C. Reactions 56213. Aromatic Substitution: Nucleophilic and Organometallic 61713.A. Mechanisms 61713.A.i. The S N Ar Mechanism 61813.A.ii. The S N 1 Mechanism 62013.A.iii. The Benzyne Mechanism 62113.A.iv. The S RN 1 Mechanism 62313.A.v. Other Mechanisms 62413.B. Reactivity 62513.B.i. The Effect of Substrate Structure 62513.B.ii. The Effect of the Leaving Group 62613.B.iii. The Effect of the Attacking Nucleophile 62613.C. Reactions 62714. Radical Reactions 67714.A. Mechanisms 67714.A.i. Radical Mechanisms in General 67714.A.ii. Free- Radical Substitution Mechanisms 68114.A.iii. Mechanisms at an Aromatic Substrate 68214.A.iv. Neighboring- Group Assistance in Free- Radical Reactions 68314.B. Reactivity 68414.B.i. Reactivity for Aliphatic Substrates 68414.B.ii. Reactivity at a Bridgehead 68814.B.iii. Reactivity in Aromatic Substrates 68914.B.iv. Reactivity in the Attacking Radical 69014.B.v. The Effect of Solvent on Reactivity 69014.C. Reactions 69115. Addition to Carbon–Carbon Multiple Bonds 71715.A. Mechanisms 71715.A.i. Electrophilic Addition 71715.A.ii. Nucleophilic Addition 71915.A.iii. Free- Radical Addition 72015.A.iv. Cyclic Mechanisms 72215.A.v. Addition to Conjugated Systems 72215.B. Orientation and Reactivity 72215.B.i. Reactivity 72215.B.ii. Orientation 72515.B.iii. Stereochemical Orientation 72715.B.iv. Addition to Cyclopropane Rings 72815.C. Reactions 72916. Addition to Carbon–Heteroatom Multiple Bonds 86916.A. Mechanism and Reactivity 86916.A.i. Nucleophilic Substitution at an Aliphatic Trigonal Carbon: The Tetrahedral Mechanism 87116.B. Reactions 87417. Elimination Reactions 100117.A. Mechanisms and Orientation 100117.A.i. The E2 Mechanism 100217.A.ii. The E1 Mechanism 100617.A.iii. The E1cB Mechanism 100717.A.iv. The E1–E2–E1cB Spectrum 101117.A.v. The E2C Mechanism 101217.B. Regiochemistry of the Double Bond 101317.C. Stereochemistry of the Double Bond 101417.D. Reactivity 101517.D.i. Effect of Substrate Structure 101517.D.ii. Effect of the Attacking Base 101717.D.iii. Influence of the Leaving Group 101717.D.iv. Influence of the Medium 101817.E. Mechanisms and Orientation in Pyrolytic Eliminations 101817.E.i. Mechanisms 101817.E.ii. Orientation in Pyrolytic Eliminations 102017.F. Reactions 102118. Rearrangements 104718.A. Mechanisms 104818.A.i. Nucleophilic Rearrangements 104818.A.ii. The Actual Nature of the Migration 104918.A.iii. Migratory Aptitudes 105118.A.iv. Memory Effects 105218.B. Longer Nucleophilic Rearrangements 105318.C. Free- Radical Rearrangements 105418.D. Carbene Rearrangements 105718.E. Electrophilic Rearrangements 105718.F. Reactions 105719. Oxidations and Reductions 112319.A. Mechanisms 112519.B. Reactions 112619.B.i. Oxidations 112619.B.ii. Reductions 1172Appendix A: the Literature of Organic Chemistry 1243Indexes 1273Author Index 1273Subject Index 1501