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 seventh 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: 7th Edition 8th Edition xv


Preface xxi


Common Abbreviations xxv


Biographical Statement xxxi


New Features of the 8th Edition xxxiii


Part I Introduction 1


1. Localized Chemical Bonding 3


1.A. Covalent Bonding 3


1.B. Multiple Valence 7


1.C. Hybridization 7


1.D. Multiple Bonds 9


1.E. Photoelectron Spectroscopy 12


1.F. Electronic Structures of Molecules 15


1.G. Electronegativity 17


1.H. Dipole Moment 19


1.I. Inductive and Field Effects 20


1.J. Bond Distances 23


1.K. Bond Angles 27


1.L. Bond Energies 29


2. Delocalized Chemical Bonding 33


2.A. Molecular Orbitals 34


2.B. Bond Energies and Distances in Compounds Containing Delocalized Bonds 37


2.C. Molecules that have Delocalized Bonds 39


2.D. Cross Conjugation 44


2.E. The Rules of Resonance 46


2.F. The Resonance Effect 48


2.G. Steric Inhibition of Resonance and the Influences of Strain 48


2.H. p -d Bonding: Ylids 52


2.I. Aromaticity 54


2.I.i. Six-Membered Rings 58


2.I.ii. Five-, Seven-, and Eight-Membered Rings 62


2.I.iii. Other Systems Containing Aromatic Sextets 67


2.J. Alternant and Nonalternant Hydrocarbons 68


2.K. Aromatic Systems with Electron Numbers Other Than Six 70


2.K.i. Systems of Two Electrons 72


2.K.ii. Systems of Four Electrons: Antiaromaticity 73


2.K.iii. Systems of Eight Electrons 76


2.K.iv. Systems of Ten Electrons 77


2.K.v. Systems of More than Ten Electrons: 4n + 2 Electrons 80


2.K.vi. Systems of More Than Ten Electrons: 4n Electrons 85


2.L. Other Aromatic Compounds 89


2.M. Hyperconjugation 92


2.N. Tautomerism 96


2.N.i. Keto-Enol Tautomerism 97


2.N.ii. Other Proton-Shift Tautomerism 100


3. Bonding Weaker Than Covalent 105


3.A. Hydrogen Bonding 105


3.B. - Interactions 113


3.C. Addition Compounds 114


3.C.i. Electron Donor-Acceptor (EDA) Complexes 114


3.C.ii. Crown Ether Complexes and Cryptates 117


3.C.iii. Inclusion Compounds 122


3.C.iv. Cyclodextrins 125


3.D. Catenanes and Rotaxanes 127


3.E. Cucurbit[n]Uril-Based Gyroscane 131


4. Stereochemistry and Conformation 133


4.A. Optical Activity and Chirality 133


4.B. Dependence of Rotation on Conditions of Measurement 135


4.C. What Kinds of Molecules Display Optical Activity? 136


4.D. The Fischer Projection 147


4.E. Absolute Configuration 148


4.E.i. The Cahn-Ingold-Prelog System 150


4.E.ii. Methods of Determining Configuration 152


4.F. The Cause of Optical Activity 156


4.G. Molecules with More Than One Stereogenic Center 157


4.H. Asymmetric Synthesis 161


4.I. Methods of Resolution 166


4.J. Optical Purity 173


4.K. Cis-Trans Isomerism 175


4.K.i. Cis-Trans Isomerism Resulting from Double Bonds 175


4.K.ii. Cis-Trans Isomerism of Monocyclic Compounds 179


4.K.iii. Cis-Trans Isomerism of Fused and Bridged Ring Systems 180


4.L. Out-In Isomerism 181


4.M. Enantiotopic and Diastereotopic Atoms, Groups, and Faces 183


4.N. Stereospecific and Stereoselective Syntheses 186


4.O. Conformational Analysis 187


4.O.i. Conformation in Open-Chain Systems 188


4.O.ii. Conformation in Six-Membered Rings 194


4.O.iii. Conformation in Six-Membered Rings Containing Heteroatoms 199


4.O.iv. Conformation in Other Rings 202


4.P. Molecular Mechanics 204


4.Q. Strain 206


4.Q.i. Strain in Small Rings 207


4.Q.ii. Strain in Other Rings 213


4.Q.iii. Unsaturated Rings 215


4.Q.iv. Strain Due to Unavoidable Crowding 218


5. Carbocations, Carbanions, Free Radicals, Carbenes, and Nitrenes 223


5.A. Carbocations 224


5.A.i. Nomenclature 224


5.A.ii. Stability and Structure of Carbocations 224


5.A.iii. The Generation and Fate of Carbocations 234


5.B. Carbanions 237


5.B.i. Stability and Structure 237


5.B.ii. The Structure of Organometallic Compounds 244


5.B.iii. The Generation and Fate of Carbanions 249


5.C. Free Radicals 250


5.C.i. Stability and Structure 250


5.C.ii. The Generation and Fate of Free Radicals 261


5.C.iii. Radical Ions 265


5.D. Carbenes 266


5.D.i. Stability and Structure 266


5.D.ii. The Generation and Fate of Carbenes 269


5.D.iii. N-Heterocyclic Carbenes (NHCs) 274


5.E. Nitrenes 276


6. Mechanisms and Methods of Determining Them 279


6.A. Types of Mechanism 279


6.B. Types of Reaction 280


6.C. Thermodynamic Requirements for Reaction 283


6.D. Kinetic Requirements for Reaction 284


6.E. The Baldwin Rules for Ring Closure 288


6.F. Kinetic and Thermodynamic Control 290


6.G. The Hammond Postulate 291


6.H. Microscopic Reversibility 291


6.I. Marcus Theory 292


6.J. Methods of Determining Mechanisms 293


6.J.i. Identification of Products 293


6.J.ii. Determination of the Presence of an Intermediate 294


6.J.iii. The Study of Catalysis 295


6.J.iv. Isotopic Labeling 296


6.J.v. Stereochemical Evidence 296


6.J.vi. Kinetic Evidence 297


6.J.vii. Isotope Effects 304


6.K. Catalyst Development 308


7. Irradiation Processes and Techniques that Influence Reactions in Organic Chemistry 313


7.A. Photochemistry 314


7.A.i. Excited States and the Ground State 314


7.A.ii. Singlet and Triplet States: "Forbidden" Transitions 316


7.A.iii. Types of Excitation 317


7.A.iv. Nomenclature and Properties of Excited States 318


7.A.v. Photolytic Cleavage 319


7.A.vi. The Fate of the Excited Molecule: Physical Processes 320


7.A.vii. The Fate of the Excited Molecule: Chemical Processes 325


7.A.viii. The Determination of Photochemical Mechanisms 330


7.B. Sonochemistry 331


7.C. Microwave Chemistry 334


7.D. Flow Chemistry 336


7.E. Mechanochemistry 338


8. Acids and Bases 339


8.A. Bronsted Theory 339


8.A.i. Bronsted Acids 340


8.A.ii. Bronsted Bases 347


8.B. The Mechanism of Proton Transfer Reactions 350


8.C. Measurements of Solvent Acidity 352


8.D. Acid and Base Catalysis 355


8.E. Lewis Acids and Bases 357


8.E.i. Hard-Soft Acids-Bases 359


8.F. The Effects of Structure on the Strengths of Acids and Bases 361


8.G. The Effects of the Medium on Acid and Base Strength 370


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 390


9.E. High Pressure 390


9.F. Water and Other Nonorganic Solvents 391


9.G. Ionic Liquid Solvents 393


9.H. Solventless Reactions 395


Part II Introduction 397


10. Aliphatic Substitution, Nucleophilic and Organometallic 403


10.A. Mechanisms 404


10.A.i. The SN2 Mechanism 404


10.A.ii. The SN1 Mechanism 410


10.A.iii. Ion Pairs in the SN1 Mechanism 414


10.A.iv. Mixed SN1 and SN2 Mechanisms 418


10.B. SET Mechanisms 420


10.C. The Neighboring-Group Mechanism 422


10.C.i. Neighboring-Group Participation by and Bonds: Nonclassical Carbocations 425


10.D. The SNi Mechanism 440


10.E. Nucleophilic Substitution at an Allylic Carbon: Allylic Rearrangements 441


10.F. Nucleophilic Substitution at an Aliphatic Trigonal Carbon: The Tetrahedral Mechanism 445


10.G. Reactivity 449


10.G.i. The Effect of Substrate Structure 449


10.G.ii. The Effect of the Attacking Nucleophile 457


10.G.iii. The Effect of the Leaving Group 464


10.G.iv. The Effect of the Reaction Medium 469


10.G.v. Phase-Transfer Catalysis 474


10.G.vi. Influencing Reactivity by External Means 477


10.G.vii. Ambident (Bidentant) Nucleophiles: Regioselectivity 478


10.G.viii. Ambident Substrates 481


10.H. Reactions 483


10.H.i. Oxygen Nucleophiles 483


10.H.ii. Sulfur Nucleophiles 506


10.H.iii. Nitrogen Nucleophiles 512


10.H.iv. Halogen Nucleophiles 534


10.H.v. Carbon Nucleophiles 545


11. Aromatic Substitution, Electrophilic 607


11.A. Mechanisms 607


11.A.i. The Arenium Ion Mechanism 608


11.A.ii. The SE1 Mechanism 613


11.B. Orientation and Reactivity 614


11.B.i. Orientation and Reactivity in Monosubstituted Benzene Rings 614


11.B.ii. The Ortho/Para Ratio 618


11.B.iii. Ipso Attack 620


11.B.iv. Orientation in Benzene Rings with More Than One Substituent 621


11.B.v. Orientation in Other Ring Systems 622


11.C. Quantitative Treatments of Reactivity in the Substrate 624


11.D. A Quantitative Treatment of Reactivity of the Electrophile: The Selectivity Relationship 626


11.E. The Effect of the Leaving Group 628


11.F. Reactions 629


11.F.i. Hydrogen as the Leaving Group in Simple Substitution Reactions 629


11.F.ii. Hydrogen as the Leaving Group in Rearrangement Reactions 675


11.F.iii. Other Leaving Groups 680


12. Aliphatic, Alkenyl, and Alkynyl Substitution: Electrophilic and Organometallic 687


12.A. Mechanisms 687


12.A.i. Bimolecular Mechanisms. SE2 and SEi 688


12.A.ii. The SE1 Mechanism 691


12.A.iii. Electrophilic Substitution Accompanied by Double-Bond Shifts 694


12.A.iv. Other Mechanisms 695


12.B. Reactivity 695


12.C. Reactions 697


12.C.i. Hydrogen as Leaving Group 697


12.C.ii. Metals as Leaving Groups 733


12.C.iii. Halogen as Leaving Group 746


12.C.iv. Carbon Leaving Groups 751


12.C.v. Electrophilic Substitution At Nitrogen 760


13. Aromatic Substitution: Nucleophilic and Organometallic 767


13.A. Mechanisms 768


13.A.i. The SNAr Mechanism 768


13.A.ii. The SN1 Mechanism 771


13.A.iii. The Benzyne Mechanism 772


13.A.iv. The SRN1 Mechanism 774


13.A.v. Other Mechanisms 776


13.B. Reactivity 776


13.B.i. The Effect of Substrate Structure 776


13.B.ii. The Effect of the Leaving Group 778


13.B.iii. The Effect of the Attacking Nucleophile 779


13.C. Reactions 779


13.C.i. All Leaving Groups Except Hydrogen and N2+ 779


13.C.ii. Hydrogen as Leaving Group 823


13.C.iii. Nitrogen as Leaving Group 824


13.C.iv. Rearrangements 834


14. Radical Reactions 839


14.A. Mechanisms 839


14.A.i. Radical Mechanisms in General 839


14.A.ii. Free-Radical Substitution Mechanisms 844


14.A.iii. Mechanisms at an Aromatic Substrate 845


14.A.iv. Neighboring-Group Assistance in Free-Radical Reactions 847


14.B. Reactivity 848


14.B.i. Reactivity for Aliphatic Substrates 848


14.B.ii. Reactivity at a Bridgehead 853


14.B.iii. Reactivity in Aromatic Substrates 854


14.B.iv. Reactivity in the Attacking Radical 855


14.B.v. The Effect of Solvent on Reactivity 856


14.C. Reactions 856


14.C.i. Hydrogen as Leaving Group 856


14.C.ii. Metals as Leaving Groups 880


14.C.iii. Halogen as Leaving Group 883


14.C.iv. Sulfur as Leaving Group 883


14.C.v. Carbon as Leaving Group 885


15. Addition to Carbon-Carbon Multiple Bonds 891


15.A. Mechanisms 892


15.A.i. Electrophilic Addition 892


15.A.ii. Nucleophilic Addition 895


15.A.iii. Free-Radical Addition 896


15.A.iv. Cyclic Mechanisms 898


15.A.v. Addition to Conjugated Systems 898


15.B. Orientation and Reactivity 899


15.B.i. Reactivity 899


15.B.ii. Orientation 902


15.B.iii. Stereochemical Orientation 904


15.B.iv. Addition to Cyclopropane Rings 906


15.C. Reactions 908


15.C.i. Isomerization of Double and Triple Bonds 908


15.C.ii. Reactions in Which Hydrogen Adds to One Side 910


15.C.iii. Reactions in Which Hydrogen Adds to Neither Side 992


15.C.iv. Cycloaddition Reactions 1027


16. Addition to Carbon-Heteroatom Multiple Bonds 1087


16.A. Mechanism and Reactivity 1087


16.A.i. Nucleophilic Substitution at an Aliphatic Trigonal Carbon: The Tetrahedral Mechanism 1089


16.B. Reactions 1094


16.B.i. Reactions in Which Hydrogen or a Metallic Ion Adds to the Heteroatom 1095


16.B.ii. Acyl Substitution Reactions 1218


16.B.iii. Reactions in Which Carbon Adds to the Heteroatom 1257


16.B.iv. Addition to Isocyanides 1264


16.B.v. Nucleophilic Substitution at a Sulfonyl Sulfur Atom 1266


17. Elimination Reactions 1273


17.A. Mechanisms and Orientation 1273


17.A.i. The E2 Mechanism 1274


17.A.ii. The E1 Mechanism 1280


17.A.iii. The E1cB Mechanism 1281


17.A.iv. The E1-E2-E1cB Spectrum 1286


17.A.v. The E2C Mechanism 1287


17.B. Regiochemistry of the Double Bond 1288


17.C. Stereochemistry of the Double Bond 1290


17.D. Reactivity 1291


17.D.i. Effect of Substrate Structure 1291


17.D.ii. Effect of the Attacking Base 1293


17.D.iii. Effect of the Leaving Group 1294


17.D.iv. Effect of the Medium 1294


17.E. Mechanisms and Orientation in Pyrolytic Eliminations 1295


17.E.i. Mechanisms 1295


17.E.ii. Orientation in Pyrolytic Eliminations 1298


17.E.iii. 1,4 Conjugate Eliminations 1298


17.F. Reactions 1299


17.F.i. Reactions in Which C C and C C Bonds are Formed 1299


17.F.ii. Fragmentations 1321


17.F.iii. Reactions in Which C N or C N Bonds are Formed 1325


17.F.iv. Reactions in Which C O Bonds are Formed 1328


17.F.v. Reactions in Which N N Bonds are Formed 1329


17.F.vi. Extrusion Reactions 1329


18. Rearrangements 1335


18.A. Mechanisms 1336


18.A.i. Nucleophilic Rearrangements 1336


18.A.ii. The Actual Nature of the Migration 1337


18.A.iii. Migratory Aptitudes 1340


18.A.iv. Memory Effects 1343


18.B. Longer Nucleophilic Rearrangements 1344


18.C. Free-Radical Rearrangements 1345


18.D. Carbene Rearrangements 1349


18.E. Electrophilic Rearrangements 1349


18.F. Reactions 1350


18.F.i. 1,2-Rearrangements 1350


18.F.ii. Non 1,2-Rearrangements 1389


19. Oxidations and Reductions 1439


19.A. Mechanisms 1440


19.B. Reactions 1442


19.B.i. Oxidations 1442


19.B.ii. Reductions 1510


Appendix A: The Literature of Organic Chemistry 1607


Appendix B: Classification of Reactions by Type of Compounds Synthesized 1645


Indexes


Author Index 1669


Subject Index 1917