Perspectives on Structure and Mechanism in Organic Chemistry

Felix A. Carroll, PhD is the Joseph R. Morton Professor of Chemistry Emeritus at Davidson College. His research focuses on organic photochemistry and photophysics, kinetics, the synthesis and characterization of insect pheromone analogues, the correlation of molecular structure with physical properties, the combustion characteristics of organic compounds, and chemical education. Dr. Carroll has published extensively in the peer-reviewed literature and was awarded a patent in the field of insect pheromones.

Preface xi

Chapter 1 Fundamental Models of Organic Chemistry 1

1.1 Atoms and Molecules 1

Basic Concepts 1

Molecular Dimensions 5

1.2 Heats of Formation and Reaction 8

Experimental Determination of Heats of Formation 8

Bond Increment Calculation of Heats of Formation 10

Group Increment Calculation of Heats of Formation 11

Heats of Formation and the Concept of Protobranching 13

Homolytic and Heterolytic Bond Dissociation Energies 15

1.3 Bonding Models 18

Electronegativity and Bond Polarity 20

Complementary Theoretical Models of Bonding 23

Pictorial Representations of Bonding Concepts 27

sp3 Hybridization 28

Are There sp3 Hybrid Orbitals in Methane? 30

Hybridization and Molecular Geometry 34

Variable Hybridization 35

1.4 Complementary Models for the Double Bond 41

The σ,π Description of Ethene 41

The Bent Bond Description of Ethene 42

Predictions of Physical Properties with the Two Models 42

1.5 The Role of Complementary Models in Organic Chemistry 46

Problems 47

Chapter 2 Introduction to Computational Chemistry 53

2.1 Hückel Molecular Orbital Theory 53

Correlation of Physical Properties with Results of HMO Calculations 63

Other Parameters Generated Through HMO Theory 67

Properties of Odd Alternant Hydrocarbons 69

The Frost Circle 74

2.2 Aromaticity 75

Benzene 77

Other Aromatic Systems 81

Polycyclic Conjugated Systems 85

Larger Annulenes 90

Dewar Resonance Energy and Absolute Hardness 93

2.3 Contemporary Computational Methods 95

Extended Hückel Theory 95

Semiempirical Methods 96

Ab Initio Theory 97

2.4 Localized Molecular Orbitals 100

Perturbational Molecular Orbital Theory 104

Atoms in Molecules 108

2.5 Density Functional Theory 112

2.6 Another Look at Valence Bond Theory 114

Resonance Structures and Resonance Energies 114

Interpreting Computational Results 117

Problems 119

Chapter 3 Stereochemistry 127

3.1 Representations of Three-Dimensional Structures 127

3.2 Stereoisomerism 130

Isomerism 130

Symmetric, Asymmetric, Dissymmetric, and Nondissymmetric Molecules 133

Fischer Projections 146

Additional Stereochemical Designations 149

3.3 Physical Manifestations of Chirality 159

Optical Activity 159

Configuration and Optical Activity 161

Other Physical Properties of Stereoisomers 166

3.4 Stereotopicity 167

Stereochemical Relationships of Substituents 167

Chirotopicity and Stereogenicity 171

Problems 172

Chapter 4 Molecular Geometry and Steric Energy 183

4.1 Designation of Molecular Conformation 183

4.2 Conformational Analysis 187

Torsional Strain 187

van der Waals Strain 191

Angle Strain and Baeyer Strain Theory 193

Application of Conformational Analysis to Cycloalkanes 194

Conformational Analysis of Substituted Cyclohexanes 198

4.3 Molecular Mechanics 204

4.4 Anomeric Effect 221

4.5 Strain and Molecular Stability 225

Problems 237

Chapter 5 Reactive Intermediates 243

5.1 Reaction Coordinate Diagrams 243

5.2 Radicals 244

Early Evidence for the Existence of Radicals 244

Detection and Characterization of Radicals 246

Structure and Bonding of Radicals 251

Thermochemical Data for Radicals 253

Generation of Radicals 255

Radical Chain Reactions 256

5.3 Carbenes 263

Structure and Geometry of Carbenes 263

Generation of Carbenes 267

Reactions of Carbenes 268

5.4 Carbocations 272

Carbonium Ions and Carbenium Ions 272

Structure and Geometry of Carbocations 274

The 2-Norbornyl Cation 281

Carbocation Rearrangements 283

Radical Cations 285

5.5 Carbanions 290

Generation of Carbanions 294

Stability of Carbanions 296

Reactions of Carbanions 296

5.6 Choosing Models of Reactive Intermediates 298

Problems 299

Chapter 6 Determining Reaction Mechanisms 305

6.1 Reaction Mechanisms 305

6.2 Methods to Determine Reaction Mechanisms 306

Identification of Reaction Products 306

Determination of Intermediates 306

Crossover Experiments 311

Isotopic Labeling 313

Stereochemical Studies 314

Solvent Effects 315

Computational Studies 317

6.3 Applications of Kinetics in Studying Reaction Mechanisms 319

6.4 Arrhenius Theory and Transition State Theory 326

6.5 Reaction Barriers and Potential Energy Surfaces 337

6.6 Kinetic Isotope Effects 348

Primary Kinetic Isotope Effects 349

Secondary Kinetic Isotope Effects 354

Tunneling and Isotope Effects 359

Solvent Isotope Effects 362

6.7 Substituent Effects 363

6.8 Linear Free Energy Relationships 368

Problems 383

Chapter 7 Acid and Base Catalysis of Organic Reactions 393

7.1 Acidity and Basicity of Organic Compounds 393

Acid–Base Measurements in Solution 393

Acid–Base Reactions in the Gas Phase 402

Comparison of Gas Phase and Solution Acidities 408

Acidity Functions 410

7.2 Acid and Base Catalysis of Chemical Reactions 413

Specific Acid Catalysis 413

General Acid Catalysis 414

Brønsted Catalysis Law 417

7.3 Acid and Base Catalysis of Reactions of Carbonyl Compounds and Carboxylic

Acid Derivatives 418

Addition to the Carbonyl Group 418

Enolization of Carbonyl Compounds 422

Hydrolysis of Acetals 426

Acid-Catalyzed Hydrolysis of Esters 428

Alkaline Hydrolysis of Esters 431

Hydrolysis of Amides 437

Problems 441

Chapter 8 Substitution Reactions 449

8.1 Introduction 449

8.2 Nucleophilic Aliphatic Substitution 450

8.3 The SN1 Reaction 453

Kinetics 453

Structural Effects in SN1 Reactions 454

Solvent Polarity and Nucleophilicity 455

Solvated Ions and Ion Pairs 459

Anchimeric Assistance in SN1 Reactions 464

Nonclassical Carbocations in SN1 Reactions 469

8.4 The SN2 Reaction 471

Stereochemistry 471

Solvent Effects 473

Substrate Effects 477

8.5 Quantitative Measures of Nucleophilicity 480

Brønsted Correlations 481

Hard–Soft Acid–Base Theory and Nucleophilicity 482

Edwards Equations 483

Swain-Scott Equation 484

Mayr Equations 485

The α-Effect 488

Leaving Group Effects in SN2 Reactions 489

Aliphatic Substitution and Single Electron Transfer 490

8.6 Electrophilic Aromatic Substitution 495

The SEAr Reaction 495

Quantitative Measurement of SEAr Rate Constants: Partial Rate Factors 498

Lewis Structures as Models of Reactivity in SEAr Reactions 500

8.7 Nucleophilic Aromatic and Vinylic Substitution 504

Nucleophilic Aromatic Substitution 504

Nucleophilic Vinylic Substitution 509

8.8 Substitution Involving Benzyne Intermediates 511

8.9 Radical-Nucleophilic Substitution 518

8.10 The Impermanence of Mechanistic Labels 521

Problems 521

Chapter 9 Elimination Reactions 529

9.1 Introduction 529

9.2 Dehydrohalogenation and Related 1,2-Elimination Reactions 534

Potential Energy Surfaces for 1,2-Elimination 534

Competition Between Substitution and Elimination 540

Stereochemistry of 1,2-Elimination Reactions 541

Elimination Reactions to Produce Alkynes 547

Regiochemistry of 1,2-Elimination Reactions 548

9.3 Other 1,2-Elimination Reactions 558

Dehalogenation of Vicinal Dihalides 558

Dehydration of Alcohols 561

Deamination of Amines 568

Pyrolytic Eliminations 572

Problems 578

Chapter 10 Addition Reactions 587

10.1 Introduction 587

10.2 Addition of Halogens to Alkenes 588

Electrophilic Addition of Bromine to Alkenes 588

Role of Charge-Transfer Complexes in Bromine Addition Reactions 592

Kinetics of Bromine Addition Reactions 593

Solvent Effects in Bromine Additions 596

Reversibility of Bromine Addition 598

Intermediates in the Addition of Bromine to Alkyl-Substituted Alkenes 599

Intermediates in the Addition of Bromine to Aryl-Substituted Alkenes 604

Summary of Bromine Addition 608

Addition of Other Halogens to Alkenes 609

10.3 Other Addition Reactions 618

Addition of Hydrogen Halides to Alkenes 618

Hydration of Alkenes 625

Oxymercuration 628

Hydroboration 632

Epoxidation 637

Electrophilic Addition to Alkynes and Cumulenes 639

Nucleophilic Addition to Alkenes and Alkynes 647

Nucleophilic Addition to Carbonyl Compounds 651

Problems 656

Chapter 11 Pericyclic Reactions 661

11.1 Introduction 661

11.2 Electrocyclic Transformations 665

Definitions and Selection Rules 665

MO Correlation Diagrams 670

State Correlation Diagrams 675

11.3 Sigmatropic Reactions 678

Selection Rules for Sigmatropic Reactions 679

Other Examples of Sigmatropic Reactions 687

11.4 Cycloaddition Reactions 691

Introduction 691

Ethene Dimerization 692

The Diels–Alder Reaction 694

Selection Rules for Cycloaddition Reactions 698

11.5 Other Pericyclic Reactions 705

Cheletropic Reactions 705

Double Group Transfer Reactions 707

Ene Reactions 709

11.6 A General Selection Rule for Pericyclic Reactions 711

11.7 Alternative Conceptual Models for Pericyclic Reactions 713

Frontier Molecular Orbital Theory 713

Hückel and Möbius Aromaticity of Transition Structures 719

Synchronous and Nonsynchronous Pericyclic Reactions 725

Potential Energy Surfaces and Ambimodal Reactions 729

11.8 Reaction Dynamics and Potential Energy Surfaces 729

Problems 735

Chapter 12 Organic Photochemistry 745

12.1 Energy and Electronic States 745

12.2 Photophysical Processes 747

Designation of Spectroscopic Transitions 748

Selection Rules for Radiative Transitions 754

Fluorescence and Phosphorescence 756

Energy Transfer and Electron Transfer 759

12.3 Photochemical Kinetics 763

Actinometry and Quantum Yield Determinations 763

Rate Constants for Unimolecular Processes 764

Transient Detection and Monitoring 765

Bimolecular Decay of Excited States: Stern–Volmer Kinetics 768

12.4 Physical Properties of Excited States 770

Acidity and Basicity in Excited States 770

Bond Angles and Dipole Moments of Excited-State Molecules 774

12.5 Representative Photochemical Reactions 777

Photochemical Reactions of Alkenes and Dienes 778

Photochemical Reactions of Carbonyl Compounds 790

Photochemical Reactions of α,ß-Unsaturated Carbonyl Compounds 798

Photochemical Reactions of Aromatic Compounds 800

Photosubstitution Reactions 802

σ Bond Photodissociation Reactions 803

Singlet Oxygen and Organic Photochemistry 808

12.6 Applications of Organic Photochemistry 811

Problems 822

References for Selected Problems 831

Index 837