Contents in Brief. Prologue 1. Appendices A-1 Glossary G-1 Credits C-1 Index I-1

Transcription

1 Contents in Brief Prologue 1 1 Structure and Bonding 7 2 Acids and Bases 58 3 Introduction to Organic Molecules and Functional Groups 86 4 Alkanes Stereochemistry Understanding Organic Reactions Alkyl Halides and Nucleophilic Substitution Alkyl Halides and Elimination Reactions Alcohols, Ethers, and Epoxides Alkenes Alkynes Oxidation and Reduction Mass Spectrometry and Infrared Spectroscopy Nuclear Magnetic Resonance Spectroscopy Radical Reactions Conjugation, Resonance, and Dienes Benzene and Aromatic Compounds Reactions of Aromatic Compounds Carboxylic Acids and the Acidity of the O H Bond Introduction to Carbonyl Chemistry; Organometallic Reagents; Oxidation and Reduction Aldehydes and Ketones Nucleophilic Addition Carboxylic Acids and Their Derivatives Nucleophilic Acyl Substitution Substitution Reactions of Carbonyl Compounds at the α Carbon Carbonyl Condensation Reactions Amines Carbon Carbon Bond-Forming Reactions in Organic Synthesis Pericyclic Reactions Carbohydrates Amino Acids and Proteins Lipids Synthetic Polymers 1225 Appendices A-1 Glossary G-1 Credits C-1 Index I-1 iv

2 Contents Preface xiii Acknowledgments xxi List of How To s xxiv List of Mechanisms xxvi List of Selected Applications xxix 2.7 Aspirin Lewis Acids and Bases 77 Key Concepts 79 Problems 80 Prologue 1 What Is Organic Chemistry? 1 Some Representative Organic Molecules 2 Organic Chemistry in the Marine Environment 4 1 Structure and Bonding The Periodic Table Bonding Lewis Structures Isomers Exceptions to the Octet Rule Resonance Determining Molecular Shape Drawing Organic Structures Hybridization Ethane, Ethylene, and Acetylene Bond Length and Bond Strength Electronegativity and Bond Polarity Polarity of Molecules L-Dopa A Representative Organic Molecule 48 Key Concepts 49 Problems 51 2 Acids and Bases Brønsted Lowry Acids and Bases Reactions of Brønsted Lowry Acids and Bases Acid Strength and pk a Predicting the Outcome of Acid Base Reactions Factors That Determine Acid Strength Common Acids and Bases 76 3 Introduction to Organic Molecules and Functional Groups Functional Groups An Overview of Functional Groups Intermolecular Forces Physical Properties Application: Vitamins Application of Solubility: Soap Application: The Cell Membrane Functional Groups and Reactivity Biomolecules 110 Key Concepts 111 Problems Alkanes Alkanes An Introduction Cycloalkanes An Introduction to Nomenclature Naming Alkanes Naming Cycloalkanes Common Names Fossil Fuels Physical Properties of Alkanes Conformations of Acyclic Alkanes Ethane Conformations of Butane An Introduction to Cycloalkanes Cyclohexane Substituted Cyclohexanes Oxidation of Alkanes Lipids Part Key Concepts 158 Problems 160 v

3 vi Contents 5 Stereochemistry Starch and Cellulose The Two Major Classes of Isomers Looking Glass Chemistry Chiral and Achiral Molecules Stereogenic Centers Stereogenic Centers in Cyclic Compounds Labeling Stereogenic Centers with R or S Diastereomers Meso Compounds R and S Assignments in Compounds with Two or More Stereogenic Centers Disubstituted Cycloalkanes Isomers A Summary Physical Properties of Stereoisomers Chemical Properties of Enantiomers 195 Key Concepts 197 Problems Understanding Organic Reactions Writing Equations for Organic Reactions Kinds of Organic Reactions Bond Breaking and Bond Making Bond Dissociation Energy Thermodynamics Enthalpy and Entropy Energy Diagrams Energy Diagram for a Two-Step Reaction Mechanism Kinetics Catalysts Enzymes 229 Key Concepts 230 Problems Alkyl Halides and Nucleophilic Substitution Introduction to Alkyl Halides Nomenclature Physical Properties Interesting Alkyl Halides The Polar Carbon Halogen Bond General Features of Nucleophilic Substitution The Leaving Group The Nucleophile Possible Mechanisms for Nucleophilic Substitution Two Mechanisms for Nucleophilic Substitution The S N 2 Mechanism Application: Useful S N 2 Reactions The S N 1 Mechanism Carbocation Stability The Hammond Postulate Application: S N 1 Reactions, Nitrosamines, and Cancer When Is the Mechanism S N 1 or S N 2? Vinyl Halides and Aryl Halides Organic Synthesis 278 Key Concepts 280 Problems Alkyl Halides and Elimination Reactions General Features of Elimination Alkenes The Products of Elimination Reactions The Mechanisms of Elimination The E2 Mechanism The Zaitsev Rule The E1 Mechanism S N 1 and E1 Reactions Stereochemistry of the E2 Reaction When Is the Mechanism E1 or E2? E2 Reactions and Alkyne Synthesis When Is the Reaction S N 1, S N 2, E1, or E2? 311 Key Concepts 315 Problems Alcohols, Ethers, and Epoxides Introduction Structure and Bonding Nomenclature 327

4 Contents vii 9.4 Physical Properties Interesting Alcohols, Ethers, and Epoxides Preparation of Alcohols, Ethers, and Epoxides General Features Reactions of Alcohols, Ethers, and Epoxides Dehydration of Alcohols to Alkenes Carbocation Rearrangements Dehydration Using POCl 3 and Pyridine Conversion of Alcohols to Alkyl Halides with HX Conversion of Alcohols to Alkyl Halides with SOCl 2 and PBr Tosylate Another Good Leaving Group Reaction of Ethers with Strong Acid Reactions of Epoxides Application: Epoxides, Leukotrienes, and Asthma Application: Benzo[a]pyrene, Epoxides, and Cancer 363 Key Concepts 363 Problems Alkenes Introduction Calculating Degrees of Unsaturation Nomenclature Physical Properties Interesting Alkenes Lipids Part Preparation of Alkenes Introduction to Addition Reactions Hydrohalogenation Electrophilic Addition of HX Markovnikov s Rule Stereochemistry of Electrophilic Addition of HX Hydration Electrophilic Addition of Water Halogenation Addition of Halogen Stereochemistry of Halogenation Halohydrin Formation Hydroboration Oxidation Keeping Track of Reactions Alkenes in Organic Synthesis 407 Key Concepts 409 Problems Alkynes Introduction Nomenclature Physical Properties Interesting Alkynes Preparation of Alkynes Introduction to Alkyne Reactions Addition of Hydrogen Halides Addition of Halogen Addition of Water Hydroboration Oxidation Reaction of Acetylide Anions Synthesis 434 Key Concepts 437 Problems Oxidation and Reduction Introduction Reducing Agents Reduction of Alkenes Application: Hydrogenation of Oils Reduction of Alkynes The Reduction of Polar C X σ Bonds Oxidizing Agents Epoxidation Dihydroxylation Oxidative Cleavage of Alkenes Oxidative Cleavage of Alkynes Oxidation of Alcohols Green Chemistry Application: The Oxidation of Ethanol Sharpless Epoxidation 471 Key Concepts 474 Problems Mass Spectrometry and Infrared Spectroscopy Mass Spectrometry Alkyl Halides and the M + 2 Peak Fragmentation Other Types of Mass Spectrometry 492

5 viii Contents 13.5 Electromagnetic Radiation Infrared Spectroscopy IR Absorptions IR and Structure Determination 505 Key Concepts 507 Problems Nuclear Magnetic Resonance Spectroscopy An Introduction to NMR Spectroscopy H NMR: Number of Signals H NMR: Position of Signals The Chemical Shift of Protons on sp 2 and sp Hybridized Carbons H NMR: Intensity of Signals H NMR: Spin Spin Splitting More Complex Examples of Splitting Spin Spin Splitting in Alkenes Other Facts About 1 H NMR Spectroscopy Using 1 H NMR to Identify an Unknown C NMR Spectroscopy Magnetic Resonance Imaging (MRI) 547 Key Concepts 548 Problems Radical Reactions Introduction General Features of Radical Reactions Halogenation of Alkanes The Mechanism of Halogenation Chlorination of Other Alkanes Chlorination Versus Bromination Halogenation as a Tool in Organic Synthesis The Stereochemistry of Halogenation Reactions Application: The Ozone Layer and CFCs Radical Halogenation at an Allylic Carbon Application: Oxidation of Unsaturated Lipids Application: Antioxidants Radical Addition Reactions to Double Bonds Polymers and Polymerization 582 Key Concepts 585 Problems Conjugation, Resonance, and Dienes Conjugation Resonance and Allylic Carbocations Common Examples of Resonance The Resonance Hybrid Electron Delocalization, Hybridization, and Geometry Conjugated Dienes Interesting Dienes and Polyenes The Carbon Carbon σ Bond Length in 1,3-Butadiene Stability of Conjugated Dienes Electrophilic Addition: 1,2- Versus 1,4-Addition Kinetic Versus Thermodynamic Products The Diels Alder Reaction Specific Rules Governing the Diels Alder Reaction Other Facts About the Diels Alder Reaction Conjugated Dienes and Ultraviolet Light 619 Key Concepts 621 Problems Benzene and Aromatic Compounds Background The Structure of Benzene Nomenclature of Benzene Derivatives Spectroscopic Properties Interesting Aromatic Compounds Benzene s Unusual Stability The Criteria for Aromaticity Hückel s Rule Examples of Aromatic Compounds What Is the Basis of Hückel s Rule? The Inscribed Polygon Method for Predicting Aromaticity Buckminsterfullerene Is it Aromatic? 655 Key Concepts 656 Problems 657

6 Contents ix 18 Reactions of Aromatic Compounds Electrophilic Aromatic Substitution The General Mechanism Halogenation Nitration and Sulfonation Friedel Crafts Alkylation and Friedel Crafts Acylation Substituted Benzenes Electrophilic Aromatic Substitution of Substituted Benzenes Why Substituents Activate or Deactivate a Benzene Ring Orientation Effects in Substituted Benzenes Limitations on Electrophilic Substitution Reactions with Substituted Benzenes Disubstituted Benzenes Synthesis of Benzene Derivatives Nucleophilic Aromatic Substitution Halogenation of Alkyl Benzenes Oxidation and Reduction of Substituted Benzenes Multistep Synthesis 705 Key Concepts 708 Problems Carboxylic Acids and the Acidity of the O H Bond Structure and Bonding Nomenclature Physical Properties Spectroscopic Properties Interesting Carboxylic Acids Aspirin, Arachidonic Acid, and Prostaglandins Preparation of Carboxylic Acids Reactions of Carboxylic Acids General Features Carboxylic Acids Strong Organic Brønsted Lowry Acids Inductive Effects in Aliphatic Carboxylic Acids Substituted Benzoic Acids Extraction Sulfonic Acids Amino Acids 741 Key Concepts 744 Problems Introduction to Carbonyl Chemistry; Organometallic Reagents; Oxidation and Reduction Introduction General Reactions of Carbonyl Compounds A Preview of Oxidation and Reduction Reduction of Aldehydes and Ketones The Stereochemistry of Carbonyl Reduction Enantioselective Carbonyl Reductions Reduction of Carboxylic Acids and Their Derivatives Oxidation of Aldehydes Organometallic Reagents Reaction of Organometallic Reagents with Aldehydes and Ketones Retrosynthetic Analysis of Grignard Products Protecting Groups Reaction of Organometallic Reagents with Carboxylic Acid Derivatives Reaction of Organometallic Reagents with Other Compounds α,β-unsaturated Carbonyl Compounds Summary The Reactions of Organometallic Reagents Synthesis 792 Key Concepts 795 Problems Aldehydes and Ketones Nucleophilic Addition Introduction Nomenclature Physical Properties Spectroscopic Properties Interesting Aldehydes and Ketones Preparation of Aldehydes and Ketones 816

7 x Contents 21.7 Reactions of Aldehydes and Ketones General Considerations Nucleophilic Addition of H and R A Review Nucleophilic Addition of CN The Wittig Reaction Addition of 1 Amines Addition of 2 Amines Addition of H 2 O Hydration Addition of Alcohols Acetal Formation Acetals as Protecting Groups Cyclic Hemiacetals An Introduction to Carbohydrates 845 Key Concepts 846 Problems Carboxylic Acids and Their Derivatives Nucleophilic Acyl Substitution Introduction Structure and Bonding Nomenclature Physical Properties Spectroscopic Properties Interesting Esters and Amides Introduction to Nucleophilic Acyl Substitution Reactions of Acid Chlorides Reactions of Anhydrides Reactions of Carboxylic Acids Reactions of Esters Application: Lipid Hydrolysis Reactions of Amides Application: The Mechanism of Action of β-lactam Antibiotics Summary of Nucleophilic Acyl Substitution Reactions Natural and Synthetic Fibers Biological Acylation Reactions Nitriles 897 Key Concepts 902 Problems Substitution Reactions of Carbonyl Compounds at the ` Carbon Introduction Enols Enolates Enolates of Unsymmetrical Carbonyl Compounds Racemization at the α Carbon A Preview of Reactions at the α Carbon Halogenation at the α Carbon Direct Enolate Alkylation Malonic Ester Synthesis Acetoacetic Ester Synthesis 940 Key Concepts 943 Problems Carbonyl Condensation Reactions The Aldol Reaction Crossed Aldol Reactions Directed Aldol Reactions Intramolecular Aldol Reactions The Claisen Reaction The Crossed Claisen and Related Reactions The Dieckmann Reaction The Michael Reaction The Robinson Annulation 974 Key Concepts 978 Problems Amines Introduction Structure and Bonding Nomenclature Physical Properties Spectroscopic Properties Interesting and Useful Amines Preparation of Amines Reactions of Amines General Features Amines as Bases 1005

8 Contents xi Relative Basicity of Amines and Other Compounds Amines as Nucleophiles Hofmann Elimination Reaction of Amines with Nitrous Acid Substitution Reactions of Aryl Diazonium Salts Coupling Reactions of Aryl Diazonium Salts Application: Synthetic Dyes Application: Sulfa Drugs 1030 Key Concepts 1031 Problems Carbon Carbon Bond- Forming Reactions in Organic Synthesis Coupling Reactions of Organocuprate Reagents Suzuki Reaction Heck Reaction Carbenes and Cyclopropane Synthesis Simmons Smith Reaction Metathesis 1056 Key Concepts 1061 Problems Pericyclic Reactions Types of Pericyclic Reactions Molecular Orbitals Electrocyclic Reactions Cycloaddition Reactions Sigmatropic Rearrangements Summary of Rules for Pericyclic Reactions 1090 Key Concepts 1091 Problems Carbohydrates Introduction Monosaccharides The Family of D-Aldoses The Family of D-Ketoses Physical Properties of Monosaccharides The Cyclic Forms of Monosaccharides Glycosides Reactions of Monosaccharides at the OH Groups Reactions at the Carbonyl Group Oxidation and Reduction Reactions at the Carbonyl Group Adding or Removing One Carbon Atom The Fischer Proof of the Structure of Glucose Disaccharides Polysaccharides Other Important Sugars and Their Derivatives 1134 Key Concepts 1139 Problems Amino Acids and Proteins Amino Acids Synthesis of Amino Acids Separation of Amino Acids Enantioselective Synthesis of Amino Acids Peptides Peptide Sequencing Peptide Synthesis Automated Peptide Synthesis Protein Structure Important Proteins 1182 Key Concepts 1185 Problems Lipids Introduction Waxes Triacylglycerols Phospholipids Fat-Soluble Vitamins Eicosanoids Terpenes Steroids 1214 Key Concepts 1219 Problems 1220

9 xii Contents 31 Synthetic Polymers Introduction Chain-Growth Polymers Addition Polymers Anionic Polymerization of Epoxides Ziegler Natta Catalysts and Polymer Stereochemistry Natural and Synthetic Rubbers Step-Growth Polymers Condensation Polymers Polymer Structure and Properties Green Polymer Synthesis Polymer Recycling and Disposal 1247 Key Concepts 1250 Problems 1251 Appendix A pk a Values for Selected Compounds A-1 Appendix B Nomenclature A-3 Appendix C Bond Dissociation Energies for Some Common Bonds [A B A + B] A-7 Appendix D Reactions that Form Carbon Carbon Bonds A-8 Appendix E Characteristic IR Absorption Frequencies A-9 Appendix F Characteristic NMR Absorptions A-10 Appendix G General Types of Organic Reactions A-12 Appendix H How to Synthesize Particular Functional Groups A-14 Glossary G-1 Credits C-1 Index I-1