Organic Chemistry ISE, 12e

Cover
Title Page
Copyright Page
About the Authors
Brief Contents
Contents
List of Important Features
Preface
Acknowledgements
CHAPTER 1 Structure Determines Properties
1.1 Atoms, Electrons, and Orbitals
Organic Chemistry: The Early Days
1.2 Ionic Bonds
1.3 Covalent Bonds, Lewis Formulas, and the Octet Rule
1.4 Polar Covalent Bonds, Electronegativity, and Bond Dipoles
Electrostatic Potential Maps
1.5 Formal Charge
1.6 Structural Formulas of Organic Molecules: Isomers
Curved Arrows and “Electron Pushing”
1.7 Resonance and Arrows
1.8 Sulfur and Phosphorus-Containing Organic Compounds and the Octet Rule
1.9 Molecular Geometries
Molecular Models and Modeling
1.10 Molecular Dipole Moments
1.11 Curved Arrows, Arrow Pushing, and Chemical Reactions
1.12 Acids and Bases: The Bronsted–Lowry View
1.13 How Structure Affects Acid Strength
1.14 Acid–Base Equilibria
1.15 Acids and Bases: The Lewis View
1.16 Summary
Problems
Descriptive Passage and Interpretive Problems 1: Amide Lewis Structural Formulas
CHAPTER 2 Alkanes and Cycloalkanes: Introduction to Hydrocarbons
2.1 Classes of Hydrocarbons
2.2 Electron Waves and Chemical Bonds
2.3 Bonding in H2: The Valence Bond Model
2.4 Bonding in H2: The Molecular Orbital Model
2.5 Introduction to Alkanes: Methane, Ethane, and Propane
2.6 sp3 Hybridization and Bonding in Methane
Methane and the Biosphere
2.7 Bonding in Ethane
2.8 sp2 Hybridization and Bonding in Ethylene
2.9 sp Hybridization and Bonding in Acetylene
2.10 Bonding in Water and Ammonia: Hybridization of Oxygen and Nitrogen
2.11 Molecular Orbitals and Bonding in Methane
2.12 Isomeric Alkanes: The Butanes
2.13 Higher n-Alkanes
2.14 The C5H12 Isomers
2.15 IUPAC Nomenclature of Unbranched Alkanes
2.16 Applying the IUPAC Rules: The Names of the C6H14 Isomers
What’s in a Name? Organic Nomenclature
2.17 Alkyl Groups
2.18 IUPAC Names of Highly Branched Alkanes
2.19 Cycloalkane Nomenclature
2.20 Introduction to Functional Groups
2.21 Sources of Alkanes and Cycloalkanes
2.22 Physical Properties of Alkanes and Cycloalkanes
2.23 Chemical Properties: Combustion of Alkanes
Thermochemistry
2.24 Oxidation–Reduction in Organic Chemistry
2.25 Summary
Problems
Descriptive Passage and Interpretive Problems 2: Some Biochemical Reactions of Alkanes
CHAPTER 3 Alkanes and Cycloalkanes: Conformations and cis–trans Stereoisomers
3.1 Conformational Analysis of Ethane
3.2 Conformational Analysis of Butane
3.3 Conformations of Higher Alkanes
Computational Chemistry: Molecular Mechanics and Quantum Mechanics
3.4 The Shapes of Cycloalkanes: Planar or Nonplanar?
3.5 Small Rings: Cyclopropane and Cyclobutane
3.6 Cyclopentane
3.7 Conformations of Cyclohexane
3.8 Axial and Equatorial Bonds in Cyclohexane
3.9 Conformational Inversion in Cyclohexane
3.10 Conformational Analysis of Monosubstituted Cyclohexanes
Enthalpy, Free Energy, and Equilibrium Constant
3.11 Disubstituted Cycloalkanes: cis–trans Stereoisomers
3.12 Conformational Analysis of Disubstituted Cyclohexanes
3.13 Medium and Large Rings
3.14 Polycyclic Ring Systems
3.15 Heterocyclic Compounds
3.16 Summary
Problems
Descriptive Passage and Interpretive Problems 3: Cyclic Forms of Carbohydrates
CHAPTER 4 Chirality
4.1 Introduction to Chirality: Enantiomers
4.2 The Chirality Center
4.3 Symmetry in Achiral Structures
4.4 Optical Activity
4.5 Absolute and Relative Configuration
4.6 Cahn–Ingold–Prelog R,S Notation
Homochirality and Symmetry Breaking
4.7 Fischer Projections
4.8 Properties of Enantiomers
Chiral Drugs
4.9 Chiral Molecules with Two Chirality Centers
4.10 Achiral Molecules with Two Chirality Centers
Chirality of Disubstituted Cyclohexanes
4.11 Molecules with Multiple Chirality Centers
4.12 Resolution of Enantiomers
4.13 The Chirality Axis
4.14 Chirality Centers Other Than Carbon
4.15 Summary
Problems
Descriptive Passage and Interpretive Problems 4: Prochirality
CHAPTER 5 Alcohols and Alkyl Halides: Introduction to Reaction Mechanisms
5.1 Functional Groups
5.2 IUPAC Nomenclature of Alkyl Halides
5.3 IUPAC Nomenclature of Alcohols
5.4 Classes of Alcohols and Alkyl Halides
5.5 Bonding in Alcohols and Alkyl Halides
5.6 Physical Properties of Alcohols and Alkyl Halides: Intermolecular Forces
5.7 Preparation of Alkyl Halides from Alcohols and Hydrogen Halides
5.8 Reaction of Alcohols with Hydrogen Halides: The SN1 Mechanism
Mechanism 5.1 Formation of tert-Butyl Chloride from tert-Butyl Alcohol and Hydrogen Chloride
5.9 Structure, Bonding, and Stability of Carbocations
5.10 Effect of Alcohol Structure on Reaction Rate
5.11 Stereochemistry and the SN1 Mechanism
5.12 Carbocation Rearrangements
Mechanism 5.2 Carbocation Rearrangement in the Reaction of 3,3-Dimethyl-2-butanol with Hydrogen Chloride
5.13 Reaction of Methyl and Primary Alcohols with Hydrogen Halides: The SN2 Mechanism
Mechanism 5.3 Formation of 1-Bromoheptane from 1-Heptanol and Hydrogen Bromide
5.14 Other Methods for Converting Alcohols to Alkyl Halides
5.15 Sulfonates as Alkyl Halide Surrogates
5.16 Summary
Problems
Descriptive Passage and Interpretive Problems 5: More About Potential Energy Diagrams
CHAPTER 6 Nucleophilic Substitution
6.1 Functional-Group Transformation by Nucleophilic Substitution
6.2 Relative Reactivity of Halide Leaving Groups
6.3 The SN2 Mechanism of Nucleophilic Substitution
Mechanism 6.1 The SN2 Mechanism of Nucleophilic Substitution
6.4 Steric Effects and SN2 Reaction Rates
6.5 Nucleophiles and Nucleophilicity
Enzyme-Catalyzed Nucleophilic Substitutions of Alkyl Halides
6.6 The SN1 Mechanism of Nucleophilic Substitution
Mechanism 6.2 The SN1 Mechanism of Nucleophilic Substitution
6.7 Stereochemistry of SN1 Reactions
6.8 Carbocation Rearrangements in SN1 Reactions
Mechanism 6.3 Carbocation Rearrangement in the SN1 Hydrolysis of 2-Bromo-3-methylbutane
6.9 Effect of Solvent on the Rate of Nucleophilic Substitution
6.10 Nucleophilic Substitution of Alkyl Sulfonates
6.11 Introduction to Organic Synthesis: Retrosynthetic Analysis
6.12 Substitution versus Elimination: A Look Ahead
6.13 Summary
Problems
Descriptive Passage and Interpretive Problems 6: Nucleophilic Substitution
CHAPTER 7 Structure and Preparation of Alkenes: Elimination Reactions
7.1 Alkene Nomenclature
7.2 Structure and Bonding in Alkenes
Ethylene
7.3 Isomerism in Alkenes
7.4 Naming Stereoisomeric Alkenes by the E–Z Notational System
7.5 Physical Properties of Alkenes
7.6 Relative Stabilities of Alkenes
7.7 Cycloalkenes
7.8 Preparation of Alkenes: Elimination Reactions
7.9 Dehydration of Alcohols
7.10 Regioselectivity in Alcohol Dehydration: The Zaitsev Rule
7.11 Stereoselectivity in Alcohol Dehydration
7.12 The E1 and E2 Mechanisms of Alcohol Dehydration
Mechanism 7.1 The E1 Mechanism for Acid-Catalyzed Dehydration of tert-Butyl Alcohol
7.13 Rearrangements in Alcohol Dehydration
Mechanism 7.2 Carbocation Rearrangement in Dehydration of 3,3-Dimethyl-2-butanol
Mechanism 7.3 Hydride Shift in Dehydration of 1-Butanol
7.14 Dehydrohalogenation of Alkyl Halides
7.15 The E2 Mechanism of Dehydrohalogenation of Alkyl Halides
Mechanism 7.4 The E2 Mechanism of 1-Chlorooctadecane
7.16 Anti Elimination in E2 Reactions: Stereoelectronic Effects
7.17 Isotope Effects and the E2 Mechanism
7.18 The E1 Mechanism of Dehydrohalogenation of Alkyl Halides
Mechanism 7.5 The E1 Mechanism for Dehydrohalogenation of 2-Bromo-2-methylbutane
7.19 Substitution and Elimination as Competing Reactions
7.20 Elimination Reactions of Sulfonates
7.21 Summary
Problems
Descriptive Passage and Interpretive Problems 7: A Mechanistic Preview of Addition Reactions
CHAPTER 8 Addition Reactions of Alkenes
8.1 Hydrogenation of Alkenes
8.2 Stereochemistry of Alkene Hydrogenation
Mechanism 8.1 Hydrogenation of Alkenes
8.3 Heats of Hydrogenation
8.4 Electrophilic Addition of Hydrogen Halides to Alkenes
Mechanism 8.2 Electrophilic Addition of Hydrogen Bromide to 2-Methylpropene
Rules, Laws, Theories, and the Scientific Method
8.5 Carbocation Rearrangements in Hydrogen Halide Addition to Alkenes
8.6 Acid-Catalyzed Hydration of Alkenes
Mechanism 8.3 Acid-Catalyzed Hydration of 2-Methylpropene
8.7 Thermodynamics of Addition–Elimination Equilibria
8.8 Hydroboration–Oxidation of Alkenes
8.9 Mechanism of Hydroboration–Oxidation
Mechanism 8.4 Hydroboration of 1-Methylcyclopentene
Mechanism 8.5 Oxidation of an Organoborane
8.10 Addition of Halogens to Alkenes
Mechanism 8.6 Bromine Addition to Cyclopentene
8.11 Epoxidation of Alkenes
Mechanism 8.7 Epoxidation of Bicyclo[2.2.1]-2-heptene
8.12 Ozonolysis of Alkenes
8.13 Enantioselective Addition to Alkenes
8.14 Retrosynthetic Analysis and Alkene Intermediates
8.15 Summary
Problems
Descriptive Passage and Interpretive Problems 8: Oxymercuration
CHAPTER 9 Alkynes
9.1 Sources of Alkynes
9.2 Nomenclature
9.3 Physical Properties of Alkynes
9.4 Structure and Bonding in Alkynes: sp Hybridization
9.5 Acidity of Acetylene and Terminal Alkynes
9.6 Preparation of Alkynes by Alkylation of Acetylene and Terminal Alkynes
9.7 Preparation of Alkynes by Elimination Reactions
9.8 Reactions of Alkynes
9.9 Hydrogenation of Alkynes
9.10 Addition of Hydrogen Halides to Alkynes
9.11 Hydration of Alkynes
Mechanism 9.1 Conversion of an Enol to a Ketone
9.12 Addition of Halogens to Alkynes
Some Things That Can Be Made from Acetylene . . . But Aren’t
9.13 Ozonolysis of Alkynes
9.14 Alkynes in Synthesis and Retrosynthesis
9.15 Summary
Problems
Descriptive Passage and Interpretive Problems 9: Thinking Mechanistically About Alkynes
CHAPTER 10 Introduction to Free Radicals
10.1 Structure, Bonding, and Stability of Alkyl Radicals
10.2 Halogenation of Alkanes
From Bond Enthalpies to Heats of Reaction
10.3 Mechanism of Methane Chlorination
Mechanism 10.1 Free-Radical Chlorination of Methane
10.4 Halogenation of Higher Alkanes
10.5 Free-Radical Addition of Hydrogen Bromide to Alkenes and Alkynes
Mechanism 10.2 Free-Radical Addition of Hydrogen Bromide to 1-Butene
10.6 Metal–Ammonia Reduction of Alkynes
Mechanism 10.3 Sodium–Ammonia Reduction of an Alkyne
10.7 Free Radicals and Retrosynthesis of Alkyl Halides
10.8 Free-Radical Polymerization of Alkenes
Mechanism 10.4 Free-Radical Polymerization of Ethylene
Ethylene and Propene: The Most Important Industrial Organic Chemicals
10.9 Summary
Problems
Descriptive Passage and Interpretive Problems 10: Free- Radical Reduction of Alkyl Halides
CHAPTER 11 Conjugation in Alkadienes and Allylic Systems
11.1 The Allyl Group
11.2 SN1 and SN2 Reactions of Allylic Halides
Mechanism 11.1 SN1 Hydrolysis of an Allylic Halide
11.3 Allylic Free-Radical Halogenation
Mechanism 11.2 Allylic Chlorination of Propene
11.4 Allylic Anions
11.5 Classes of Dienes: Conjugated and Otherwise
11.6 Relative Stabilities of Dienes
11.7 Bonding in Conjugated Dienes
11.8 Bonding in Allenes
11.9 Preparation of Dienes
Diene Polymers
11.10 Addition of Hydrogen Halides to Conjugated Dienes
Mechanism 11.3 Addition of Hydrogen Chloride to 1,3-Cyclopentadiene
11.11 Halogen Addition to Dienes
11.12 The Diels–Alder Reaction
11.13 Intramolecular Diels–Alder Reactions
11.14 Retrosynthetic Analysis and the Diels–Alder Reaction
11.15 Molecular Orbital Analysis of the Diels–Alder Reaction
Pericyclic Reactions in Chemical Biology
11.16 The Cope and Claisen Rearrangements
11.17 Summary
Problems
Descriptive Passage and Interpretive Problems 11: 1,3-Dipolar Cycloaddition
CHAPTER 12 Arenes and Aromaticity
12.1 Benzene
12.2 The Structure of Benzene
12.3 The Stability of Benzene
12.4 Bonding in Benzene
12.5 Substituted Derivatives of Benzene and Their Nomenclature
12.6 Polycyclic Aromatic Hydrocarbons
Fullerenes, Nanotubes, and Graphene
12.7 Physical Properties of Arenes
12.8 The Benzyl Group
12.9 Nucleophilic Substitution in Benzylic Halides
Triphenylmethyl Radical Yes, Hexaphenylethane No
12.10 Benzylic Free-Radical Halogenation
12.11 Benzylic Anions
12.12 Oxidation of Alkylbenzenes
12.13 Alkenylbenzenes
12.14 Polymerization of Styrene
Mechanism 12.1 Free-Radical Polymerization of Styrene
12.15 The Birch Reduction
Mechanism 12.2 The Birch Reduction
12.16 Benzylic Side Chains and Retrosynthetic Analysis
12.17 Cyclobutadiene and Cyclooctatetraene
12.18 Huckel’s Rule
12.19 Annulenes
12.20 Aromatic Ions
12.21 Heterocyclic Aromatic Compounds
12.22 Heterocyclic Aromatic Compounds and Huckel’s Rule
12.23 Summary
Problems
Descriptive Passage and Interpretive Problems 12: Substituent Effects on Reaction Rates and Equilibria
CHAPTER 13 Electrophilic and Nucleophilic Aromatic Substitution
13.1 Representative Electrophilic Aromatic Substitution Reactions of Benzene
13.2 Mechanistic Principles of Electrophilic Aromatic Substitution
13.3 Nitration of Benzene
Mechanism 13.1 Nitration of Benzene
13.4 Sulfonation of Benzene
Mechanism 13.2 Sulfonation of Benzene
13.5 Halogenation of Benzene
Mechanism 13.3 Bromination of Benzene
Biosynthetic Halogenation
13.6 Friedel–Crafts Alkylation of Benzene
Mechanism 13.4 Friedel–Crafts Alkylation
13.7 Friedel–Crafts Acylation of Benzene
Mechanism 13.5 Friedel–Crafts Acylation
13.8 Synthesis of Alkylbenzenes by Acylation–Reduction
13.9 Rate and Regioselectivity in Electrophilic Aromatic Substitution
13.10 Rate and Regioselectivity in the Nitration of Toluene
13.11 Rate and Regioselectivity in the Nitration of (Trifluoromethyl)benzene
13.12 Substituent Effects in Electrophilic Aromatic Substitution: Activating Substituents
13.13 Substituent Effects in Electrophilic Aromatic Substitution: Strongly Deactivating Substituents
13.14 Substituent Effects in Electrophilic Aromatic Substitution: Halogens
13.15 Multiple Substituent Effects
13.16 Retrosynthetic Analysis and the Synthesis of Substituted Benzenes
13.17 Substitution in Naphthalene
13.18 Substitution in Heterocyclic Aromatic Compounds
13.19 Nucleophilic Aromatic Substitution
13.20 The Addition–Elimination Mechanism of Nucleophilic Aromatic Substitution
Mechanism 13.6 Nucleophilic Aromatic Substitution in p-Fluoronitrobenzene by the Addition–Elimination Mechanism
13.21 Related Nucleophilic Aromatic Substitutions
13.22 Summary
Problems
Descriptive Passage and Interpretive Problems 13: Benzyne
CHAPTER 14 Spectroscopy
14.1 Principles of Molecular Spectroscopy: Electromagnetic Radiation
14.2 Principles of Molecular Spectroscopy: Quantized Energy States
14.3 Introduction to 1H NMR Spectroscopy
14.4 Nuclear Shielding and 1H Chemical Shifts
14.5 Effects of Molecular Structure on 1H Chemical Shifts
Ring Currents: Aromatic and Antiaromatic
14.6 Interpreting 1H NMR Spectra
14.7 Spin–Spin Splitting and 1H NMR
14.8 Splitting Patterns: The Ethyl Group
14.9 Splitting Patterns: The Isopropyl Group
14.10 Splitting Patterns: Pairs of Doublets
14.11 Complex Splitting Patterns
14.12 1H NMR Spectra of Alcohols
Magnetic Resonance Imaging (MRI)
14.13 NMR and Conformations
14.14 13C NMR Spectroscopy
14.15 13C Chemical Shifts
14.16 13C NMR and Peak Intensities
14.17 13C1H Coupling
14.18 Using DEPT to Count Hydrogens
14.19 2D NMR: COSY and HETCOR
14.20 Introduction to Infrared Spectroscopy
Spectra by the Thousands
14.21 Infrared Spectra
14.22 Characteristic Absorption Frequencies
14.23 Ultraviolet-Visible Spectroscopy
14.24 Mass Spectrometry
14.25 Molecular Formula as a Clue to Structure
14.26 Summary
Problems
Descriptive Passage and Interpretive Problems 14: More on Coupling Constants
CHAPTER 15 Organometallic Compounds
15.1 Organometallic Nomenclature
15.2 Carbon–Metal Bonds
15.3 Preparation of Organolithium and Organomagnesium Compounds
15.4 Organolithium and Organomagnesium Compounds as Bronsted Bases
15.5 Synthesis of Alcohols Using Grignard and Organolithium Reagents
15.6 Synthesis of Acetylenic Alcohols
15.7 Retrosynthetic Analysis and Grignard and Organolithium Reagents
15.8 An Organozinc Reagent for Cyclopropane Synthesis
Mechanism 15.1 Similarities Between the Mechanisms of Reaction of an Alkene with lodomethylzinc lodide and a Peroxy Acid
15.9 Carbenes and Carbenoids
15.10 Transition-Metal Organometallic Compounds
An Organometallic Compound That Occurs Naturally: Coenzyme B12
15.11 Organocopper Reagents
15.12 Palladium-Catalyzed Cross-Coupling
15.13 Homogeneous Catalytic Hydrogenation
Mechanism 15.2 Homogeneous Catalysis of Alkene Hydrogenation
15.14 Olefin Metathesis
Mechanism 15.3 Olefin Cross-Metathesis
15.15 Ziegler–Natta Catalysis of Alkene Polymerization
Mechanism 15.4 Polymerization of Ethylene in the Presence of Ziegler–Natta Catalyst
15.16 Summary
Problems
Descriptive Passage and Interpretive Problems 15: Allylindium Reagents
CHAPTER 16 Alcohols, Diols, and Thiols
16.1 Sources of Alcohols
16.2 Preparation of Alcohols by Reduction of Aldehydes and Ketones
16.3 Preparation of Alcohols by Reduction of Carboxylic Acids
16.4 Preparation of Alcohols from Epoxides
16.5 Preparation of Diols
16.6 Reactions of Alcohols: A Review and a Preview
16.7 Conversion of Alcohols to Ethers
Mechanism 16.1 Acid-Catalyzed Formation of Diethyl Ether from Ethyl Alcohol
16.8 Esterification
16.9 Oxidation of Alcohols
Sustainability and Organic Chemistry
16.10 Biological Oxidation of Alcohols
16.11 Oxidative Cleavage of Vicinal Diols
16.12 Thiols
16.13 Spectroscopic Analysis of Alcohols and Thiols
16.14 Summary
Problems
Descriptive Passage and Interpretive Problems 16: The Pinacol Rearrangement
CHAPTER 17 Ethers, Epoxides, and Sulfides
17.1 Nomenclature of Ethers, Epoxides, and Sulfides
17.2 Structure and Bonding in Ethers and Epoxides
17.3 Physical Properties of Ethers
17.4 Crown Ethers
17.5 Preparation of Ethers
Polyether Antibiotics
17.6 The Williamson Ether Synthesis
17.7 Reactions of Ethers: A Review and a Preview
17.8 Acid-Catalyzed Cleavage of Ethers
Mechanism 17.1 Cleavage of Ethers by Hydrogen Halides
17.9 Preparation of Epoxides
17.10 Conversion of Vicinal Halohydrins to Epoxides
17.11 Reactions of Epoxides with Anionic Nucleophiles
Mechanism 17.2 Nucleophilic Ring Opening of an Epoxide
17.12 Acid-Catalyzed Ring Opening of Epoxides
Mechanism 17.3 Acid-Catalyzed Ring Opening of an Epoxide
17.13 Epoxides in Biological Processes
17.14 Preparation of Sulfides
17.15 Oxidation of Sulfides: Sulfoxides and Sulfones
17.16 Alkylation of Sulfides: Sulfonium Salts
17.17 Spectroscopic Analysis of Ethers, Epoxides, and Sulfides
17.18 Summary
Problems
Descriptive Passage and Interpretive Problems 17: Epoxide Rearrangements and the NIH Shift
CHAPTER 18 Aldehydes and Ketones: Nucleophilic Addition to the Carbonyl Group
18.1 Nomenclature
18.2 Structure and Bonding: The Carbonyl Group
18.3 Physical Properties
18.4 Sources of Aldehydes and Ketones
18.5 Reactions of Aldehydes and Ketones: A Review and a Preview
18.6 Principles of Nucleophilic Addition: Hydration of Aldehydes and Ketones
Mechanism 18.1 Hydration of an Aldehyde or Ketone in Basic Solution
Mechanism 18.2 Hydration of an Aldehyde or Ketone in Acid Solution
18.7 Cyanohydrin Formation
Mechanism 18.3 Cyanohydrin Formation
18.8 Reaction with Alcohols: Acetals and Ketals
Mechanism 18.4 Acetal Formation from Benzaldehyde and Ethanol
18.9 Acetals and Ketals as Protecting Groups
18.10 Reaction with Primary Amines: Imines
Mechanism 18.5 Imine Formation from Benzaldehyde and Methylamine
18.11 Reaction with Secondary Amines: Enamines
Imines in Biological Chemistry
Mechanism 18.6 Enamine Formation
18.12 The Wittig Reaction
18.13 Stereoselective Addition to Carbonyl Groups
18.14 Oxidation of Aldehydes
18.15 Spectroscopic Analysis of Aldehydes and Ketones
18.16 Summary
Problems
Descriptive Passage and Interpretive Problems 18: The Baeyer–Villiger Oxidation
CHAPTER 19 Carboxylic Acids
19.1 Carboxylic Acid Nomenclature
19.2 Structure and Bonding
19.3 Physical Properties
19.4 Acidity of Carboxylic Acids
19.5 Substituents and Acid Strength
19.6 Ionization of Substituted Benzoic Acids
19.7 Salts of Carboxylic Acids
19.8 Dicarboxylic Acids
19.9 Carbonic Acid
19.10 Sources of Carboxylic Acids
19.11 Synthesis of Carboxylic Acids by the Carboxylation of Grignard Reagents
19.12 Synthesis of Carboxylic Acids by the Preparation and Hydrolysis of Nitriles
19.13 Reactions of Carboxylic Acids: A Review and a Preview
19.14 Mechanism of Acid-Catalyzed Esterification
Mechanism 19.1 Acid-Catalyzed Esterification of Benzoic Acid with Methanol
19.15 Intramolecular Ester Formation: Lactones
19.16 Decarboxylation of Malonic Acid and Related Compounds
Enzymatic Decarboxylation of a β-Keto Acid
19.17 Spectroscopic Analysis of Carboxylic Acids
19.18 Summary
Problems
Descriptive Passage and Interpretive Problems 19: Lactonization Methods
CHAPTER 20 Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution
20.1 Nomenclature of Carboxylic Acid Derivatives
20.2 Structure and Reactivity of Carboxylic Acid Derivatives
Reaction Trends: Aldehydes and Ketones vs. Carboxylic Acid Derivatives
20.3 Nucleophilic Acyl Substitution Mechanisms
20.4 Nucleophilic Acyl Substitution in Acyl Chlorides
20.5 Nucleophilic Acyl Substitution in Acid Anhydrides
Mechanism 20.1 Nucleophilic Acyl Substitution in an Anhydride
20.6 Physical Properties and Sources of Esters
20.7 Reactions of Esters: A Preview
20.8 Acid-Catalyzed Ester Hydrolysis
Mechanism 20.2 Acid-Catalyzed Ester Hydrolysis
20.9 Ester Hydrolysis in Base: Saponification
The Ball Method
Mechanism 20.3 Ester Hydrolysis in Basic Solution
20.10 Reaction of Esters with Ammonia and Amines
20.11 Reaction of Esters with Grignard and Organolithium Reagents and Lithium Aluminum Hydride
20.12 Amides
20.13 Hydrolysis of Amides
Mechanism 20.4 Amide Hydrolysis in Acid Solution
Mechanism 20.5 Amide Hydrolysis in Basic Solution
20.14 Lactams
β-Lactam Antibiotics
20.15 Preparation of Nitriles
20.16 Hydrolysis of Nitriles
Mechanism 20.6 Nitrile Hydrolysis in Basic Solution
20.17 Addition of Grignard Reagents to Nitriles
20.18 Spectroscopic Analysis of Carboxylic Acid Derivatives
20.19 Summary
Problems
Descriptive Passage and Interpretive Problems 20: Thioesters
CHAPTER 21 Enols and Enolates
21.1 Aldehyde, Ketone, and Ester Enolates
21.2 The Aldol Condensation
Mechanism 21.1 Aldol Addition of Butanal
21.3 Mixed and Directed Aldol Reactions
From the Mulberry Tree to Cancer Chemotherapy
21.4 Acylation of Enolates: The Claisen and Related Condensations
Mechanism 21.2 Claisen Condensation of Ethyl Propanoate
21.5 Alkylation of Enolates: The Acetoacetic Ester and Malonic Ester Syntheses
21.6 Enol Content and Enolization
Mechanism 21.3 Acid-Catalyzed Enolization of 2-Methylpropanal
21.7 The Haloform Reaction
Mechanism 21.4 The Haloform Reaction
21.8 Some Chemical and Stereochemical Consequences of Enolization
21.9 Conjugation Effects in α,β-Unsaturated Aldehydes and Ketones
21.10 Summary
Problems
Descriptive Passage and Interpretive Problems 21: The Knoevenagel Reaction
CHAPTER 22 Amines
22.1 Amine Nomenclature
22.2 Structure and Bonding
22.3 Physical Properties
22.4 Basicity of Amines
Amines as Natural Products
22.5 Tetraalkylammonium Salts as Phase-Transfer Catalysts
22.6 Reactions That Lead to Amines: A Review and a Preview
22.7 Preparation of Amines by Alkylation of Ammonia
22.8 The Gabriel Synthesis of Primary Alkylamines
22.9 Preparation of Amines by Reduction
Mechanism 22.1 Lithium Aluminum Hydride Reduction of an Amide
22.10 Reductive Amination
22.11 Reactions of Amines: A Review and a Preview
22.12 Reaction of Amines with Alkyl Halides
22.13 The Hofmann Elimination
22.14 Electrophilic Aromatic Substitution in Arylamines
22.15 Nitrosation of Alkylamines
22.16 Nitrosation of Arylamines
22.17 Synthetic Transformations of Aryl Diazonium Salts
22.18 Azo Coupling
From Dyes to Sulfa Drugs
22.19 Spectroscopic Analysis of Amines
22.20 Summary
Problems
Descriptive Passage and Interpretive Problems 22: Synthetic Applications of Enamines
CHAPTER 23 Carbohydrates
23.1 Classification of Carbohydrates
23.2 Fischer Projections and d,l Notation
23.3 The Aldotetroses
23.4 Aldopentoses and Aldohexoses
23.5 A Mnemonic for Carbohydrate Configurations
23.6 Cyclic Forms of Carbohydrates: Furanose Forms
23.7 Cyclic Forms of Carbohydrates: Pyranose Forms
23.8 Mutarotation
Mechanism 23.1 Acid-Catalyzed Mutarotation of d-Glucopyranose
23.9 Carbohydrate Conformation: The Anomeric Effect
23.10 Ketoses
23.11 Deoxy Sugars
23.12 Amino Sugars
23.13 Branched-Chain Carbohydrates
23.14 Glycosides: The Fischer Glycosidation
Mechanism 23.2 Preparation of Methyl d-Glucopyranosides by Fischer Glycosidation
23.15 Disaccharides
23.16 Polysaccharides
How Sweet It Is!
23.17 Application of Familiar Reactions to Monosaccharides
23.18 Oxidation of Carbohydrates
23.19 Glycosides: Synthesis of Oligosaccharides
Mechanism 23.3 Silver-Assisted Glycosidation
23.20 Glycobiology
Oligosaccharides in Infectious Disease
23.21 Summary
Problems
Descriptive Passage and Interpretive Problems 23: Emil Fischer and the Structure of (+)-Glucose
CHAPTER 24 Lipids
24.1 Acetyl Coenzyme A
24.2 Fats, Oils, and Fatty Acids
24.3 Fatty Acid Biosynthesis
24.4 Phospholipids
24.5 Waxes
24.6 Prostaglandins
Nonsteroidal Antiinflammatory Drugs (NSAIDs) and COX-2 Inhibitors
24.7 Terpenes: The Isoprene Rule
24.8 Isopentenyl Diphosphate: The Biological Isoprene Unit
24.9 Carbon–Carbon Bond Formation in Terpene Biosynthesis
24.10 The Pathway from Acetate to Isopentenyl Diphosphate
24.11 Steroids: Cholesterol
Mechanism 24.1 Biosynthesis of Cholesterol from Squalene
24.12 Vitamin D
Good Cholesterol? Bad Cholesterol? What’s the Difference?
24.13 Bile Acids
24.14 Corticosteroids
24.15 Sex Hormones
24.16 Carotenoids
Crocuses Make Saffron from Carotenes
24.17 Summary
Problems
Descriptive Passage and Interpretive Problems 24: Polyketides
CHAPTER 25 Amino Acids, Peptides, and Proteins
25.1 Classification of Amino Acids
25.2 Stereochemistry of Amino Acids
25.3 Acid–Base Behavior of Amino Acids
Electrophoresis
25.4 Synthesis of Amino Acids
25.5 Reactions of Amino Acids
25.6 Peptides
25.7 Introduction to Peptide Structure Determination
25.8 Amino Acid Analysis
25.9 Partial Hydrolysis and End Group Analysis
25.10 Insulin
25.11 Edman Degradation and Automated Sequencing of Peptides
Mechanism 25.1 The Edman Degradation
25.12 Mass Spectrometry of Peptides and Proteins
Peptide Mapping and MALDI Mass Spectrometry
25.13 The Strategy of Peptide Synthesis
25.14 Amino and Carboxyl Group Protection and Deprotection
25.15 Peptide Bond Formation
Mechanism 25.2 Amide Bond Formation Between a Carboxylic Acid and an Amine Using N,N′-Dicyclohexylcarbodiimide
25.16 Solid-Phase Peptide Synthesis: The Merrifield Method
25.17 Secondary Structures of Peptides and Proteins
25.18 Tertiary Structure of Polypeptides and Proteins
25.19 Protein Quaternary Structure: Hemoglobin
25.20 Enzymes
Mechanism 25.3 Carboxypeptidase-Catalyzed Hydrolysis
25.21 Coenzymes in Reactions of Amino Acids
Mechanism 25.4 Pyridoxal 5′-Phosphate-Mediated Decarboxylation of an α-Amino Acid
Mechanism 25.5 Transamination: Biosynthesis of l-Alanine from l-Glutamic Acid and Pyruvic Acid
Oh NO! It’s Inorganic!
25.22 G-Protein-Coupled Receptors
25.23 Summary
Problems
Descriptive Passage and Interpretive Problems 25: Amino Acids in Enantioselective Synthesis
CHAPTER 26 Nucleosides, Nucleotides, and Nucleic Acids
26.1 Pyrimidines and Purines
26.2 Nucleosides
26.3 Nucleotides
26.4 Bioenergetics
26.5 ATP and Bioenergetics
26.6 Phosphodiesters, Oligonucleotides, and Polynucleotides
26.7 Phosphoric Acid Esters
26.8 Deoxyribonucleic Acids
“It Has Not Escaped Our Notice . . .”
26.9 Secondary Structure of DNA: The Double Helix
26.10 Replication of DNA
26.11 Ribonucleic Acids
mRNA Therapeutics
26.12 Protein Biosynthesis
26.13 DNA Sequencing
26.14 Summary
Problems
Descriptive Passage and Interpretive Problems 26: Oligonucleotide Synthesis
CHAPTER 27 Synthetic Polymers
27.1 Some Background
From Bakelite to Nylon
27.2 Polymer Nomenclature
27.3 Classification of Polymers: Reaction Type
27.4 Classification of Polymers: Chain Growth and Step Growth
27.5 Classification of Polymers: Structure
27.6 Classification of Polymers: Properties
27.7 Addition Polymers: A Review and a Preview
27.8 Chain Branching in Free-Radical Polymerization
Mechanism 27.1 Branching in Polyethylene Caused by Intramolecular Hydrogen Transfer
Mechanism 27.2 Branching in Polyethylene Caused by Intermolecular Hydrogen Transfer
27.9 Anionic Polymerization: Living Polymers
Mechanism 27.3 Anionic Polymerization of Styrene
27.10 Cationic Polymerization
Mechanism 27.4 Cationic Polymerization of 2-Methylpropene
27.11 Polyamides
27.12 Polyesters
27.13 Polycarbonates
27.14 Polyurethanes
27.15 Copolymers
Conducting Polymers
27.16 Summary
Problems
Descriptive Passage and Interpretive Problems 27: Chemically Modified Polymers
Appendix: Summary of Methods Used to Synthesize a Particular Functional Group
Glossary
Index