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. ppi-dpi 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. pi-pi 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. Brønsted Theory 339

8.A.i. Brønsted Acids 340

8.A.ii. Brønsted 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 pi and sigma 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...