Chemistry. Organic. A Mechanistic Approach. Penny Chaloner. CRC Press. J Taylor & Francis Group Boca Raton London New York QJ*"

Transcription

1 Organic Chemistry A Mechanistic Approach Penny Chaloner ^ QJ*" CRC Press J Taylor & Francis Group Boca Raton London New York CRC Press is an imprint of the Taylor & Francis Croup, an informa business

2 Contents Preface Acknowledgments Author xvii xix xxi Chapter 1 Review of Atomic and Molecular Structure Introduction Atomic and Molecular Structure Orbitals of the Hydrogen Atom Multielectron Atoms Bonding 8 Review Problems 11 Chapter 2 Alkanes and Friends: Structure, Bonding, Properties, and Nomenclature Introduction Hybridization in Methane, Ammonia, and Water Drawing Molecules Introduction to Alkanes Formal Nomenclature of Alkanes Structural Isomers and Formal Nomenclature Haloalkanes Cycloalkanes Stability, Strain, and Properties of Alkanes and Cycloalkanes 31 Review Problems 33 Chapter 3 Alkenes, Alkynes, and Aromatic Compounds Alkenes Bonding in Alkenes Nomenclature of Alkenes Geometric Isomerism in Alkenes Stability of Alkenes and the Effect of Conjugation Aromatic Hydrocarbons Bonding in Aromatic Compounds Nomenclature of Benzene Derivatives Alkynes: Hydrocarbons Containing Triple Bonds Resonance 66 Review Problems 71 Chapter 4 Heteroatom-Containing Functional Groups Compounds Containing sp3 Nitrogen Atoms Molecules Containing sp2 Nitrogen Atoms Molecules with sp-hybridized Nitrogen Compounds Containing sp3 Oxygen Alcohols Ethers Crown Ethers, lonophores, and the Solvation of Metal Ions 91 vii

3 viii Contents 4.5 Compounds Containing sp2 Oxygen Aldehydes Ketones Carboxylic Acids Carboxylate Esters Amides Acyl Halides and Anhydrides Priorities in Nomenclature Structure and Bonding in Some Highly Reactive Species Carbocations Carbanions Carbon-Centered Radicals More Resonance 112 Review Problems 113 More Challenging Problems 118 Chapter 5 Purification and Identification of Organic Compounds Introduction Purification of Organic Compounds Crystallization Distillation and Sublimation Chromatography Mass Spectrometry UWVisible Spectroscopy Infrared Spectroscopy Introduction and Theory Regions of the Infrared Spectrum 154 Review Problems 169 More Challenging Problems 171 Chapter 6 Identification of Organic Compounds 2: Nuclear Magnetic Resonance Spectroscopy Introduction Chemical Shifts Spin-Spin Coupling Simple Aliphatic Systems Spin-Spin Coupling Involving Protons Attached to sp2 Carbon Atoms Spin-Spin Decoupling Protons Attached to Oxygen and Nitrogen ,3C NMR Spectroscopy 209 Review Problems 215 More Challenging Problems 219 Chapter 7 Stereochemistry Introduction Conformations of Alkanes Cycloalkanes Cyclopropane Cyclobutane Cyclopentane Six-Membered Rings Medium and Large Rings Ring Synthesis 233

4 Contents ix 7.4 Chirality Absolute Configuration Molecules with More than One Chiral Center Chiral Molecules with Noncarbon Chiral Centers Other Chiral Compounds Fischer Projections 255 Review Problems 259 More Challenging Problems 262 Chapter 8 Introduction to Mechanism Introduction Studying Organic Reaction Mechanisms Thermodynamics Kinetics Study of Products Isotopic Labeling and Kinetic Isotope Effects Study of Intermediates Classification of Reactions Acids and Bases Orbital Effects Electronegativity Inductive Effects Derealization Solvation Hydrogen Bonding Steric Effects Aromaticity Tautomers: A Slight Digression Writing Mechanisms Using Curly Arrows 296 Review Problems 304 More Challenging Problems 311 Chapter 9 Nucleophilic Substitution at Saturated Carbon Introduction Mechanistic Types Stereochemical Implications Effect of Nucleophile Effect of the Leaving Group Effect of Substrate Structure SN1 Reactions SN2 Reactions Effect of Solvents Competing Reactions Competition between SN1 and SN2 Processes Applications and Scope of the Reaction Halide Ions as Nucleophiles Oxygen and Sulfur as Nucleophiles Nitrogen Nucleophiles Carbon Nucleophiles Neighboring Group Participation and Intramolecular Reactions 365 Review Problems 369 More Challenging Problems 376

5 x Contents Chapter 10 Elimination Reactions Introduction Mechanisms El Elimination, Unimolecular E2 Elimination, Bimolecular E1cB Elimination, Unimolecular, Conjugate Base Stereochemistry E1 Eliminations E2 Eliminations E1cB Eliminations Regiochemistry Effect of Substrate Substitution versus Elimination Carbocation Rearrangements Examples and Applications E1 Reactions E2 Reactions ElcB Reactions Mixed or Variable Mechanisms Elimination to Give Alkynes Other Elimination Reactions 406 Review Problems 410 More Challenging Proolems 416 Chapter 11 Addition Reactions Introduction Electrophilic Reactions Reaction Mechanism Scope of the Reaction Electrophilic Addition to Conjugated Dienes Terpenes: Biology Oligomerizes Dienes Electrophilic Addition to Alkynes Radical Addition Reactions Multicenter Processes Epoxidation Using Peracids Carbene Addition Hydroboration Dihydroxylation of Alkenes Ozonolysis Cycloadditions, Diels-Alder Reactions Hydrogenation 478 Review Problems 484 More Challenging Problems 493 Chapter 12 Electrophilic Aromatic Substitution Introduction Electrophiles Protons Carbocations Halogens Nitration Sulfonation Orientation Effects Inductive Donors Resonance Donors 514

6 Contents xi Resonance Acceptors Halogens Two or More Groups in Conflict Partial Rate Factors Reactions of Polycyclic Aromatic Compounds Heterocyclic Aromatic Compounds Pyridine and Related Compounds Analogues of the Cyclopentadienyl Anion 532 Review Problems 536 More Challenging Problems 544 Chapter 13 Nucleophilic Aromatic Substitution and Synthesis of Aromatic Compounds Introduction Unimolecular Nucleophilic Substitution of Aromatic Compounds: The Reactions of Diazonium Salts with Simple Nucleophiles Azo Coupling Reactions Nucleophilic Substitution of Aryl Halides, SN2Ar Substitution of Haloheterocycles Substitution via Benzyne and Related Intermediates Reactions in Side Chains of Aromatic Compounds Reactions of Alkylbenzenes Reduction of Nitro Groups Reduction of Aryl Ketones Reduction of Benzene Rings Carbon-Aryl Bond Formation Friedel-Crafts Alkylation and Acylation Haloalkylation Reactions Reactions of Grignard Reagents Nucleophilic Substitution by Cyanide Aromatic Synthesis 582 Review Problems 590 More Challenging Problems 599 Chapter 14 Addition to Carbon-Heteroatom Double Bonds Introduction and Review Mechanism of Addition Reactions Reversible Addition Reactions Cyanohydrin Formation Hydrates, Hemiacetals, and Acetals Acetals and Thioacetals Imines, Enamines, Oximes, and Hydrazones Irreversible Addition Reactions Replacement of Carbonyl Oxygen by Hydrogen Addition of Hydride: Reduction to Alcohols or Amines Addition of Carbon Nucleophiles Wittig Reactions 648 Review Problems 652 More Challenging Problems 660 Chapter 15 Substitution of Carbonyl Compounds: Carboxylic Acids and Their Derivatives Introduction: Review of Nomenclature Substitution Reaction Effect of Substrate Effect of Leaving Group 672

7 xii Contents 15.3 Oxygen Nucleophiles Nitrogen Nucleophiles Synthesis of Acid Chlorides Hydride as Nucleophile Carbon Nucleophiles Grignard Reagents Organolithium Compounds Organocadmium Compounds Organozinc Compounds: The Reformatskii Reaction Organocopper Reagents 701 Review Problems 703 More Challenging Problems 712 Chapter 16 Lipids and Carbohydrates Introduction Lipids Surfactants Fatty Acids and Triglycerides Prostaglandins Waxes Steroids Carbohydrates Introduction Triose Sugars Tetrose Sugars Pentose Sugars Hexose Sugars Cyclic Forms of Sugars Substitution of the OH Groups of Sugars Oxidation Reactions Reduction Chain Lengthening and Shortening Reactions Disaccharides Polysaccharides 768 Review Problems 770 More Challenging Problems 775 Chapter 17 Substitution a and p to Carbonyl Groups Introduction Formation of Enolsand Enolates Isomerizations Involving Enolsand Enolates Reactions of Enols and Enolates with Electrophiles Reaction with Halogens Aldol Reaction Claisen Ester Condensation Alkylation of p-dicarbonyl Compounds Alkylation of Simple Ketones Reactions of Enamines Revisiting the Reformatskii Reaction Two Useful Reactions of Nonenolizable Carbonyl Compounds Reactions at the p-position of a,p-unsaturated Carbonyl Compounds and Other Electron-Poor Alkenes Reactions of Enones with Simple Nucleophiles Conjugate Addition to Other Electron-Poor Alkenes Epoxidation of Electron-Poor Alkenes Organometallic Nucleophiles 825

8 Contents xiii Addition of Enolate Anions to Enones Robinson Annulation: A Look Ahead to Synthesis 830 Review Problems 833 More Challenging Problems 842 Chapter 18 Rearrangement Reactions Introduction Migration to Electron-Deficient Carbon Carbocation Rearrangements Pinacol and Semipinacol Rearrangements Dienone-Phenol Rearrangements Migration to Electron-Deficient Nitrogen Beckmann Rearrangement Hofmann Degradation: A Chain-Shortening Reaction Migration to Electron-Deficient Oxygen: The Baeyer-Villiger Oxidation Anionic Rearrangements Neutral Rearrangements Electrocyclic Reactions Sigmatropic Rearrangements 875 Review Problems 884 More Challenging Problems 893 Chapter 19 Synthesis 1: One-Group Disconnections Introduction Simple Disconnections and the Retrosynthetic Approach One-Group Disconnections Disconnection of Alcohols Disconnections of Alkenes FGIs and Disconnections Leading to Aldehydes and Ketones FGIs and Disconnections to Prepare Carboxylic Acids 929 Review Problems 932 More Challenging Problems 937 Chapter 20 Synthesis 2: Two-Group Disconnections and Protecting Groups Introduction to Two-Group Disconnections ,2-Difunctionalized Compounds Addition to Double Bonds Acyl Anion Equivalents Radical Coupling Reactions Other Reactions ,3-Difunctionalized Compounds p-hydroxyketones: The Aldol Condensation oc,p-unsaturated Aldehydes and Ketones ,3-Diketones p-ketoesters Two Important Synthons for Ester Enolates ,4-Difunctionalized Compounds ,5-Difunctionalized Compounds Robinson Annulation ,6-Difunctionalized Compounds Pericyclic Disconnections Protecting Groups Protection of Aldehydes and Ketones Protection of Alcohols 980

9 xiv Contents Protection of 1,2- and 1,3-Diols Protection of Carboxylic Acids Protection of Amines 985 Further Reading 986 Review Problems 986 More Challenging Problems 995 Chapter 21 Polymeric Materials Introduction Polymer Structures Preparation of Addition or Chain-Growth Polymers Radical Polymerization Cationic Polymerization Anionic Polymerization Metal-Mediated Polymerizations Scope of Polymerization of Substituted Alkenes Polymerization of Dienes Ring-Opening Polymerization Preparation of Step-Reaction Polymers Polyesters and Polycarbonates Polyamides Other Polymers Unusual Biopolymers It's a Sticky Business Chewing It Over Pretty as a Picture 1036 Review Problems 1038 More Challenging Problems 1043 Chapter 22 Amines, Alkaloids, Amino Acids, Peptides, and Nucleic Acids Synthesis of Amines Syntheses Involving Nucleophilic Substitution Syntheses from Amides Reduction and Addition at Carbon-Nitrogen Double Bonds Reduction of Nitro Compounds Alkaloids Amino Acids Synthesis of Amino Acids Resolution of Amino Acids Reactions of Amino Acids Peptides Structures of Peptides and Proteins Synthesis Analysis of Peptides Nucleic Acids 1083 Review Problems 1090 More Challenging Problems 1097 Chapter 23 Catalysis of Organic Reactions Introduction Catalysis by Acids and Bases Lewis Acid Catalysis Reactions of Carbonyl Compounds Catalysis of Diels-Alder Reactions.'. 1110

10 Contents xv 23.4 Phase-Transfer Catalysis Reactions Catalyzed by Metal Surfaces Reactions Catalyzed by Transition Metal Complexes Wacker Oxidation and Related Reactions Homogeneous Hydrogenation Coupling Reactions Organocatalysis Enzyme Catalysis 1134 Review Problems 1139 More Challenging Problems 1143 Chapter 24 Organic Chemistry in Industry Introduction Process Chemistry versus Research Chemistry Pharmaceutical Industry Introduction Drug Discovery Drug Development: Preclinical Testing Drug Development: Clinical Testing Personalized Medicine The Future: Problems and Opportunities Agrochemicals Herbicides Fungicides Insecticides Dyes and Colorants Textile Dyes Food Dyes 1170 Review Problems 1173 Further Reading 1174 Chapter 25 Organic Chemistry and the Environment Introduction Pesticides Endocrine Disruptors Chlorofluorocarbons and Their Replacements Polycyclic Aromatic Hydrocarbons Plastics: Recycle, Degrade, or Burn? Is "Green Chemistry" the Future? 1192 Review Problems 1196 Further Reading 1197 Chapter 26 Organic Chemistry in Forensic Science Introduction Drugs of Abuse Categories of Drugs of Abuse Presumptive Tests for Drugs of Abuse Instrumental Methods Designer Drugs Poisons and Poisoning Testing for Blood Dyes, Inks, and Paper 1224

11 xvi Contents 26.6 Trace Evidence Visualization of Fingerprints 1232 Review Problems 1234 Appendix A: Glossary of Abbreviations and Acronyms 1239 Appendix B: Some Common/Trivial Names You Need to Know 1247 Index 1249