ORGANIC CHEMISTRY T. W. GRAHAM SOLOMONS. University of South Florida. JOHN WlLEY & SONS, INC. New York Chichester Brisbane Toronto Singapore

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1 SIXTH EDITION ORGANIC CHEMISTRY T. W. GRAHAM SOLOMONS University of South Florida JOHN WlLEY & SONS, INC. New York Chichester Brisbane Toronto Singapore

2 CONTENTS CHAPTER 1 CARBON COMPOUNDS AND CHEMICAL BONDS 1.1 Introduction Development of Organic Chemistry as a Science The Structural Theory of Organic Chemistry Chemical Bonds: The Octet Rule Writing Lewis Structures Exceptions to the Octet Rule Formal Charge Resonance Energy Changes Quantum Mechanics Atomic Orbitals Molecular Orbitals The Structure of Methane: sp 3 Hybridization The Structure of Borane: sp 2 Hybridization The Structure of Beryllium Hydride: sp Hybridization A Summary of Important Concepts that Come from Quantum Mechanics Molecular Geometry: The Valence Shell Electron-Pair Repulsion (VSEPR) Model Polar Covalent Bonds Polar and Nonpolar Molecules Representation of Structural Formulas 41 CHAPTER 2 REPRESENTATIVE CARBON COMPOUNDS 2.1 Carbon-Carbon Covalent Bonds Methane and Ethane: Representative Alkanes Alkenes: Compounds Containing the Carbon-Carbon Double Bond; Ethene and Propene Orbital Hybridization and the Structure of Alkenes Alkynes: Compounds Containing the Carbon-Carbon Triple Bond; Ethyne (Acetylene) and Propyne Orbital Hybridization and the Structure of Alkynes Benzene: A Representative Aromatic Hydrocarbon Functional Groups Alkyl Halides or Haloalkanes Alcohols 67 xvii

3 XVÜi CONTENTS 2.11 Ethers Amines Aldehydes and Ketones Carboxylic Acids, Amides, and Esters Summary of Important Families of Organic Compounds Physical Properties and Molecular Structure Summary of Attractive Electric Forces 83 CHAPTER3 AN INTRODUCTION TO ORGANIC REACTIONS: ACIDS AND BASES 3.1 Reactions and Their Mechanisms Acid-Base Reactions Heterolysis of Bonds to Carbon: Carbocations and Carbanions The Use of Curved Arrows in Illustrating Reactions The Strength of Acids and Bases: K a and pk a Predicting the Outcome of Acid-Base Reactions The Relationship between Structure and Acidity The Relationship between the Equilibrium Constant and the Standard Free- Energy Change, AG The Acidity of Carboxylic Acids The Effect of the Solvent on Acidity Organic Compounds as Bases A Mechanism for an Organic Reaction Acids and Bases in Nonaqueous Solutions 7/ Acid-Base Reactions and the Synthesis of Deuterium- and Tritium-Labeled Compounds Some Important Terms and Concepts 118 CHAPTER 4 ALKANES AND CYCLOALKANES. CONFORMATIONS OF MOLECULES 4.1 Introduction to Alkanes and Cycloalkanes Shapes of Alkanes IUPAC Nomenclature of Alkanes, Alkyl Halides, and Alcohols Nomenclature of Cycloalkanes Physical Properties of Alkanes and Cycloalkanes Sigma Bonds and Bond Rotation Conformational Analysis of Butane The Relative Stabilities of Cycloalkanes: Ring Strain The Origin of Ring Strain in Cyclopropane and Cyclobutane: Angle Strain and Torsional Strain Conformations of Cyclohexane Substituted Cyclohexanes: Axial and Equatorial Hydrogen Atoms Disubstituted Cycloalkanes: eis-trans Isomerism Bicyclic and Polycyclic Alkanes Chemical Reactions of Alkanes Synthesis of Alkanes and Cycloalkanes 165

4 4.16 Planning Organic Syntheses Pheromones: Communication by Means of Chemicals Some Important Terms and Concepts 173 CHAPTER 5 STEREOCHEMISTRY. CHIRAL MOLECULES 5.1 Isomerism: Constitutional Isomers and Stereoisomers Enantiomers and Chiral Molecules The Biological Importance of Chirality Historical Origin of Stereochemistry Tests for Chirality: Planes of Symmetry Nomenclature of Enantiomers: The (R-S) System Properties of Enantiomers: Optical Activity The Origin of Optical Activity The Synthesis of Enantiomers Chiral Drugs Molecules with More than One Stereocenter Fischer Projection Formulas Stereoisomerism of Cyclic Compounds Relating Configurations through Reactions in which No Bonds to the Stereocenter are Broken Separation of Enantiomers: Resolution Compounds with Stereocenters Other than Carbon Chiral Molecules that Do Not Possess a Tetrahedral Atom with Four Different Groups Some Important Terms and Concepts 220 CHAPTER 6 IONIC REACTIONS NUCLEOPHILIC SUBSTITUTION AND ELIMINATION REACTIONS OF ALKYL HALIDES 6.1 Introduction Physical Properties of Organic Halides Nucleophilic Substitution Reactions Nucleophiles Leaving Groups Thermodynamics and Kinetics of Chemical Reactions 229 h.l Kinetics of a Nucleophilic Substitution Reaction: An S N 2 Reaction A Mechanism for the S N 2 Reaction Transition State Theory: Free-Energy Diagrams The Stereochemistry of S N 2 Reactions The Reaction of terf-butyl Chloride with Hydroxide Ion: An S N 1 Reaction A Mechanism for the S N 1 Reaction Carbocations The Stereochemistry of S N 1 Reactions Factors Affecting the Rates of S N 1 and S N 2 Reactions Org anic Synthesis: Functional Group Transformations Using S N 2 Reactions Elimination Reactions of Alkyl Halides 260

5 XX CONTENTS 6.18 The E2 Reaction The El Reaction Substitution versus Elimination Overall Summary Some Important Terms and Concepts 269 SPECIAL TOPIC A BlOLOGICAL A/lETHYLATION. BlOCHEMICAL NUCLEOPHILIC SUBSTITUTION REACTIONS 277 SPECIAL TOPIC ß NEIGHBORING GROUP PARTICIPATION IN NUCLEOPHILIC SUBSTITUTION REACTIONS 280 CHAPTER 7 ALKENES AND ALKYNES l. PROPERTIES AND SYNTHESIS 7.1 Introduction Nomenclature of Alkenes and Cycloalkenes Nomenclature of Alkynes Physical Properties of Alkenes and Alkynes Hydrogenation of Alkenes Hydrogenation: The Function of the Catalyst Hydrogenation of Alkynes Molecular Formulas of Hydrocarbons: The Index of Hydrogen Deficiency Relative Stabilities of Alkenes Cycloalkenes Synthesis of Alkenes via Elimination Reactions Dehydrohalogenation of Alkyl Halides Dehydration of Alcohols Carbocation Stability and the Transition State Carbocation Stability and the Occurrence of Molecular Rearrangements Alkenes by Debromination of Vicinal Dibromides Summary of Methods for the Preparation of Alkenes Synthesis of Alkynes by Elimination Reactions The Acidity of Terminal Alkynes Replacement of the Acetylenic Hydrogen Atom of Terminal Alkynes 321 CHAPTER 8 ALKENES AND ALKYNES II. ADDITION REACTIONS 8.1 Introduction: Addition to Alkenes Addition of Hydrogen Halides to Alkenes: Markovnikov's Rule Stereochemistry of the Ionic Addition to an Alkene Addition of Sulfuric Acid to Alkenes Addition of Water to Alkenes: Acid-Catalyzed Hydration Addition of Bromine and Chlorine to Alkenes Stereochemistry of the Addition of Halogens to Alkenes Halohydrin Formation Oxidations of Alkenes: Syn Hydroxylation Oxidative Cleavage of Alkenes Summary of Addition Reactions of Alkenes 351

6 CONTENTS xxi 12 Addition of Bromine and Chlorine to Alkynes Addition of Hydrogen Halides to Alkynes Oxidative Cleavage of Alkynes Summary of Addition Reactions of Alkynes Synthetic Strategies Revisited Simple Chemical Tests for Alkanes, Alkenes, Alkynes, Alkyl Halides, and Alcohols 359 CHAPTER9 RADICAL REACTIONS 9.1 Introduction Homolytic Bond Dissociation Energies The Reactions of Alkanes with Halogens Chlorination of Methane: Mechanism of Reaction Chlorination of Methane: Energy Changes Halogenation of Higher Alkanes The Geometry of Alkyl Radicals Reactions that Generate Tetrahedral Stereocenters Radical Addition to Alkenes: The An ti-marko vnikov Addition of Hydrogen Bromide Radical Polymerization of Alkenes: Chain-Growth Polymers Other Important Radical Chain Reactions Some Important Terms and Concepts 401 SPECIAL TOPIC c CHAIN-GROWTH POLYMERS 404 SPECIAL TOPIC D DIVALENT CARBON COMPOUNDS: CARBENES 412 CHAPTER 10 ALCOHOLS AND ETHERS 10.1 Structure and Nomenclature Physical Properties of Alcohols and Ethers Important Alcohols and Ethers Synthesis of Alcohols from Alkenes Alcohols from Alkenes through Oxymercuration-Demercuration Hydroboration: Synthesis of Organoboranes Alcohols from Alkenes through Hydroboration-Oxidation Reactions of Alcohols Alcohols as Acids Conversion of Alcohols into Mesylates and Tosylates Mesylates and Tosylates in S N 2 Reactions Alkyl Phosphates Conversion of Alcohols into Alkyl Halides Alkyl Halides from the Reactions of Alcohols with Hydrogen Halides Alkyl Halides from the Reactions of Alcohols with PBr 3 or SOCl Synthesis of Ethers Reactions of Ethers Epoxides 448

7 XXÜ CONTENTS Reactions of Epoxides Anti Hydroxylation of Alkenes via Epoxides Summary of Reactions of Alcohols and Ethers Crown Ethers: Nucleophilic Substitution Reactions in Relatively Nonpolar Aprotic Solvents by Phase-Transfer Catalysis 458 CHAPTER 1 1 ALCOHOLS FROM CARBONYL COMPOUNDS, OXIDATION- REDUCTION AND ORGANOMETALLIC COMPOUNDS 11.1 Introduction Oxidation-Reduction Reactions in Organic Chemistry Alcohols by Reduction of Carbonyl Compounds Oxidation of Alcohols Organometallic Compounds Preparation of Organolithium and Organomagnesium Compounds Reactions of Organolithium and Organomagnesium Compounds Alcohols from Grignard Reagents 484 CHAPTER 1 2 CONJUGATED UNSATURATED SYSTEMS 12.1 Introduction Allylic Substitution and the Allyl Radical The Stability of the Allyl Radical The Allyl Cation Summary of Rules for Resonance Alkadienes and Polyunsaturated Hydrocarbons ,3-Butadiene: Electron Delocalization The Stability of Conjugated Dienes Electrophilic Attack on Conjugated Dienes: 1,4 Addition The Diels-Alder Reaction: A 1,4-Cycloaddition Reaction of Dienes 520 FIRST REVIEW PROBLEM SET 530 CHAPTER 1 3 SPECTROSCOPIC METHODS OF STRUCTURE DETERMINATION 13.1 Introduction. The Electromagnetic Spectrum Visible and Ultraviolet Spectroscopy Infrared Spectroscopy Nuclear Magnetic Resonance Spectroscopy Nuclear Spin: The Origin of the Signal Shielding and Deshielding of Protons The Chemical Shift Chemical Shift Equivalent and Nonequivalent Protons Signal Splitting: Spin-Spin Coupling Proton NMR Spectra and Rate Processes Carbon-13 NMR Spectroscopy Magnetic Resonance Imaging in Medicine 577

8 CONTENTS XXÜi SPECIAL TOPic E TWO-DIMENSIONAL (2D) NMR TECHNIQUES 585 SPECIAL TOPIC F MASS SPECTROMETRY 589 SPECIAL TOPIC G THE PHOTOCHEMISTRY OF VISION 610 CHAPTER 14 AROMATIC COMPOUNDS 14.1 Introduction Nomenclature of Benzene Derivatives Reactions of Benzene The Kekule Structure for Benzene The Stability of Benzene Modern Theories of the Structure of Benzene Hückel's Rule: The {An + 2) TT Electron Rule Other Aromatic Compounds Heterocyclic Aromatic Compounds Aromatic Compounds in Biochemistry Spectroscopy of Aromatic Compounds A Summary of Important Terms and Concepts 646 CHAPTER 1 5 REACTIONS OF AROMATIC COMPOUNDS 15.1 Electrophilic Aromatic Substitution Reactions A General Mechanism for Electrophilic Aromatic Substitution: Arenium Ions Halogenation of Benzene Nitration of Benzene Sulfonation of Benzene Friedel-Crafts Alkylation Friedel-Crafts Acylation Limitations of Friedel-Crafts Reactions Synthetic Applications of Friedel-Crafts Acylations. The Clemmensen Reduction Effect of Substituents on Reactivity and Orientation Theory of Substituent Effects on Electrophilic Aromatic Substitution Reactions of the Side Chain of Alkylbenzenes Alkenylbenzenes Synthetic Applications Allylic and Benzylic Halides in Nucleophilic Substitution Reactions Reduction of Aromatic Compounds: The Birch Reduction 697 CHAPTER 16 ALDEHYDES AND KETONES I. NUCLEOPHILIC ADDITIONS TO THE CARBONYL GROUP 16.1 Introduction Nomenclature of Aldehydes and Ketones Physical Properties 706

9 XXJV CONTENTS 16.4 Synthesis of Aldehydes Synthesis of Ketones Nucleophilic Addition to the Carbon-Oxygen Double Bond The Addition of Water and Alcohols: Hydrates and Acetals The Addition of Derivatives of Ammonia The Addition of Hydrogen Cyanide The Addition of Ylides: The Wittig Reaction The Addition of Organometallic Reagents: The Reformatsky Reaction Oxidation of Aldehydes and Ketones Chemical Analysis of Aldehydes and Ketones Spectroscopic Properties of Aldehydes and Ketones Summary of the Addition Reactions of Aldehydes and Ketones 745 CHAPTER 1 7 ALDEHYDES AND KETONES II. ALDOL REACTIONS 17.1 The Acidity of the a Hydrogens of Carbonyl Compounds: Enolate Ions Keto and Enol Tautomers Reactions via Enols and Enolate Ions The Haloform Reaction The Aldol Reaction: The Addition of Enolate Ions to Aldehydes and Ketones Crossed Aldol Reactions Cyclizations via Aldol Condensations Acid-Catalyzed Aldol Condensations Additions to a,/3-unsaturated Aldehydes and Ketones 774 SPECIAL TOPIC H LITHIUM ENOLATES IN ORGANIC SYNTHESIS 784 CHAPTER 1 8 CARBOXYLIC ACIDS AND THEIR DERIVATIVES. NUCLEOPHILIC SUBSTITUTION AT THE ACYL CARBON 18.1 Introduction Nomenclature and Physical Properties Preparation of Carboxylic Acids Nucleophilic Substitutions at the Acyl Carbon Acyl Chlorides Carboxylic Acid Anhydrides Esters Amides a-halo Acids: The Hell-Volhard-Zelinski Reaction Derivatives of Carbonic Acid Decarboxylation of Carboxylic Acids Chemical Tests for Acyl Compounds Summary of the Reactions of Carboxylic Acids and Their Derivatives 835 SPECIAL TOPIC i STEP-GROWTH POLYMERS 849

10 CONTENTS XXV CHAPTER 1 9 SYNTHESIS AND REACTIONS OF /3-DICARBONYL COMPOUNDS: MORE CHEMISTRY OF ENOLATE IONS 19.1 Introduction The Claisen Condensation: The Synthesis of /3-Keto Esters The Acetoacetic Ester Synthesis: Synthesis of Substituted Acetones 19.4 The Malonic Ester Synthesis: Synthesis of Substituted Acetic Acids 19.5 Further Reactions of Active Hydrogen Compounds Direct Alkylation of Esters and Nitriles Alkylation of 1,3-Dithianes The Knoevenagel Condensation Michael Additions The Mannich Reaction Synthesis of Enamines: Stork Enamine Reactions Barbiturates Summary of Important Reactions 890 CHAPTER 2 0 AMINES 20.1 Nomenclature Physical Properties and Structure of Amines Basicity of Amines: Amine Salts Some Biologically Important Amines Preparation of Amines Reactions of Amines Reactions of Amines with Nitrous Acid Replacement Reactions of Arenediazonium Salts Coupling Reaction of Arenediazonium Salts Reactions of Amines with Sulfonyl Chlorides The Sulfa Drugs: Sulfanilamide Analysis of Amines Eliminations Involving Ammonium Compounds Summary of Preparations and Reactions of Amines 942 SPECIAL TOPIC J REACTIONS AND SYNTHESIS OF HETEROCYCLIC AMINES 952 CHAPTER 2 1 PHENOLS AND ARYL HALIDES: NUCLEOPHILIC AROMATIC SUBSTITUTION 21.1 Structure and Nomenclature of Phenols Naturally Occurring Phenols Physical Properties of Phenols Synthesis of Phenols Reactions of Phenols as Acids Other Reactions of the O H Group of Phenols Cleavage of Alkyl Aryl Ethers 973

11 XXVi CONTENTS 21.8 Reactions of the Benzene Ring of Phenols The Claisen Rearrangement Quinones Aryl Halides and Nucleophilic Aromatic Substitution Spectroscopic Analysis of Phenols and Aryl Halides Summary of Important Reactions 986 SECOND REVIEW PROBLEM SET 993 SPECIAL TOPIC K ALKALOIDS 999 SPECIAL TOPIC L THIOLS, THIOETHERS, AND THIOPHENOLS 1006 SPECIAL TOPIC M COMPOUNDS 1012 TRANSITION METAL ORGANOMETALLIC SPECIAL TOPIC N ORGANIC HALIDES AND ORGANOMETALLIC COMPOUNDS IN THE ENVIRONMENT 1024 SPECIAL TOPIC O ELECTROCYCLIC AND CYCLOADDITION REACTIONS 1030 CHAPTER 22 CARBOHYDRATES 22.1 Introduction Monosaccharides Mutarotation Glycoside Formation Reactions of Monosaccharides Oxidation Reactions of Monosaccharides Reduction of Monosaccharides: Alditols Reactions of Monosaccharides with Phenylhydrazine: Osazones Synthesis and Degradation of Monosaccharides The D-Family of Aldoses Fischer's Proof of the Configuration of D-(+)-Glucose Disaccharides Polysaccharides Other Biologically Important Sugars Sugars That Contain Nitrogen Glycolipids and Glycoproteins of the Cell Surface Carbohydrate Antibiotics 7087 CHAPTER 23 LlPIDS 23.1 Introduction Fatty Acids and Triacylglycerols Terpenes and Terpenoids Steroids Prostaglandins 7777

12 CONTENTS XXVÜ 23.6 Phospholipids and Cell Membranes Waxes 1122 SPECIAL TOPIC P THIOL ESTERS AND LIPID BIOSYNTHESIS 1128 CHAPTER 24 AMINO ACIDS AND PROTEINS 24.1 Introduction Amino Acids Laboratory Synthesis of a-amino Acids Analysis of Polypeptides and Proteins Amino Acid Sequence of Polypeptides and Proteins Primary Structures of Polypeptides and Proteins Polypeptide and Protein Synthesis Secondary and Tertiary Structures of Proteins Introduction to Enzymes Lysozyme: Mode of Action of an Enzyme Serine Proteases Hemoglobin: A Conjugated Protein 1183 CHAPTER 25 NUCLEIC ACIDS AND PROTEIN SYNTHESIS 25.1 Introduction Nucleotides and Nucleosides Laboratory Synthesis of Nucleosides and Nucleotides Deoxyribonucleic Acid: DNA 7/ RNA and Protein Synthesis Determining the Base Sequence of DNA Laboratory Synthesis of Oligonucleotides The Polymerase Chain Reaction 1216 ANSWERS TO SELECTED PROBLEMS A-l GLOSSARY G-1 INDEX i-i