For full-year courses in organic chemistry taken by science and pre-health professions majors. This innovative text from acclaimed educator Paula Bruice is organized in a way that discourages rote memorization. It highlights mechanistic similarities and ties synthesis and reactivity togetherteaching the reactivity of a functional group and the synthesis of compounds obtained as a result of that reactivity. Bruice's writing has been praised for anticipating students' questions and appeals to their need to learn visually and by solving problems. Emphasizing that students should reason their way to solutions rather than memorize facts, Bruice encourages students to think about what they have learned previously and apply that knowledge in a new setting. The text balances coverage of traditional topics with bioorganic chemistry, recognizing the importance of bioorganic topics to today's students.
(NOTE: Each chapter concludes with Key Terms and Problems. Chapters 3, 7-11, 14-20, and 27 conclude with a Summary of Reactions`.)
I. AN INTRODUCTION TO THE STUDY OF ORGANIC CHEMISTRY.
1. Electronic Structures and Bonding. Acids and Bases.
The Structure of an Atom. Distribution of Electrons in an Atom. Ionic, Covalent, and Polar Bonds. Lewis Structures. Atomic Orbitals. Molecular Orbitals and Bonding. Bonding in Methane and Ethane. Single Bonds. Bonding in Ethane. Double Bonds. Bonding in the Ethyne. Bonding in the Methyl Cation, the Methyl Radical, and the Methyl Anion. Bonding in Water. Bonding in Ammonia and in the Ammonium Ion. Bonding in the Hydrogen Halides. Summary of Orbital Hybridization, Bond Lengths, Bond Strengths, and Bond Angles. Dipole Moments of Molecules. An Introduction to Acids and Bases. Organic Acids and Bases: pKa and pH. The Effect of Structure on pKa. An Introduction to Delocalized Electrons and Resonance. The Effect of pH on the Structure of an Organic Compound. Lewis Acids and Bases. 2. An Introduction to Organic Compounds: Nomenclature, Physical Properties, and Representation of Structure.
Nomenclature of Alkyl Substituents. Nomenclature of Alkanes. Nomenclature of Cycloalkanes. Nomenclature of Alkyl Halides. Nomenclature of Ethers. Nomenclature of Alcohols. Nomenclature of Amines. Structure of Alkyl Halides, Alcohols, Ethers, and Amines. Physical Properties of Alkanes, Alkyl Halides, Alcohols. Ethers, and Amines. Conformations of Alkanes: Rotation about Carbon—Carbon Bonds. Cycloalkanes: Ring Strain. Conformations of Cyclohexane. Conformations of Monosubstituted Cyclohexanes. Conformations of Disubstituted Cyclohexanes. Conformations of Fused Rings.
II. HYDROCARBONS, STEREOCHEMISTRY, AND RESONANCE.
3. Reactions of Alkenes. Thermodynamics and Kinetics.
General Molecular Formula for a Hydrocarbon. Nomenclature of Alkenes. The Structure of Alkenes. Cis-Trans Isomerism. The E,Z System of Nomenclature. Reactivity Considerations. Thermodynamics and Kinetics. General Mechanism for Electrophilic Addition Reactions. Addition of Hydrogen Halides. Carbocation Stability. The Structure of the Transition State. Regioselectivity of Electrophilic Addition Reactions: Markovnikov's Rule. Addition of Water and Alcohols. Rearrangement of Carbocations. Addition of Halogens. Oxymercuration-Demercuration. Addition of Borane: Hydroboration-Oxidation. Addition of Radicals. The Relative Stabilities of Radicals. Addition of Hydrogen. The Relative Stabilities of Alkenes. Reactions and Synthesis. 4. Stereochemistry: The Arrangement of Atoms in Space; The Stereochemistry of Addition Reactions.
Conformational Isomers. Configurational Isomers: Cis-Trans Isomers. Configurational Isomers: Isomers with One Chirality Center. Drawing Enantiomers. Naming Enantiomers: The R, S System of Nomenclature. Optical Rotation. Optical Purity. Isomers with More Than One Chirality Center. Meso Compounds. The R, S System of Nomenclature for Isomers with More Than One Chirality Center. Reactions of Compounds That Contain a Chirality Center. Determining the Configuration. Separation of Enantiomers. Enantiotopic Hydrogens. Diastereotopic Hydrogens. and Prochirality Centers. Nitrogen and Phosphorus Chirality Centers. Stereochemistry of Reactions: Regioselective, Stereoselective, and Stereospecific Reactions. Stereochemistry of Alkene Addition Reactions. Stereochemistry of Enzyme-Catalyzed Reactions. 5. Reactions of Alkynes. Introduction to Multistep Synthesis.
Nomenclature of Alkynes. Physical Properties of Unsaturated Hydrocarbons. The Structure of Alkynes. Reactivity Considerations. Addition of Hydrogen Halides and Addition of Halogens. Addition of Water. Addition of Borane: Hydroboration-Oxidation. Addition of Hydrogen. Acidity of a Hydrogen Bonded to an sp Hybridized Carbon. Synthesis Using Acetylide Ions. Designing a Synthesis I: An Introduction to Multistep Synthesis. Commercial Use of Ethyne. 6. Electron Delocalization and Resonance.
Delocalized Electrons: The Structure of Benzene. Bonding in Benzene. Delocalized Electrons and Resonance. How to Draw Resonance Contributors. The Resonance Hybrid. Resonance Energy. Stability of Allylic and Benzylic Cations. Stability of Allylic and Benzylic Radicals. Some Chemical Consequences of Electron Delocalization. Effect of Delocalized Electrons on pKa. A Molecular Orbital Description of Stability. 7. Reactions of Dienes.
Nomenclature of Alkenes with More Than One Functional Group. Configurational Isomers of Dienes. Relative Stabilities of Dienes. A Molecular Orbital Description of 1,3-Butadiene. Reactivity Considerations. Electrophilic Addition Reactions of Isolated Dienes. Electrophilic Addition Reactions of Conjugated Dienes. Thermodynamic versus Kinetic Control of Reactions. Addition of a Dienophile to a Conjugated Diene: The Diels-Alder Reaction. Nomenclature of Bicyclic Compounds. 8. Reactions of Alkanes: Radicals.
Reactivity Considerations. Chlorination and Bromination of Alkanes. Factors That Determine Product Distribution. The Reactivity-Selectivity Principle. Radical Substitution of Benzylic and Allylic Hydrogens. Stereochemistry of Radical Substitution Reactions. Reaction of Cyclic Compounds. Radical Reactions in Biological Systems. Radicals and Stratospheric Ozone.
III. SUBSTITUTION AND ELIMINATION REACTIONS.
9. Reactions at an sp3 Hybridized Carbon I: Substitution Reactions of Alkyl Halides.
Reactivity Considerations. The Mechanism of SN2 Reactions. The SN2 Reaction. The Reversibility of an SN2 Reaction. The Mechanism of SN1 Reactions. The SN1 Reaction. The Stereochemistry of SN2 and SN1 Reactions. Benzylic Halides, Allylic Halides, Vinylic Halides, and Aryl Halides. Competition between SN2 and SN1 Reactions. The Role of the Solvent in SN2 and SN1 Reactions. Biological Methylating Agents. 10. Reactions at an sp3 Hybridized Carbon II: Elimination Reactions of Alkyl Halides; Competition between Substitution and Elimination.
The E2 Reaction. Zaitsev's Rule. The E1 Reaction. Competition between E2 and E1 Reactions. Stereochemistry of E2 and E1 Reactions. Elimination from Cyclic Compounds. A Kinetic Isotope Effect. Competition between Substitution and Elimination. Substitution and Elimination Reactions in Synthesis. Consecutive E2 Elimination Reactions. Intermolecular versus Intramolecular Reactions. Designing a Synthesis II: Approaching the Problem. 11. Reactions at sp3 Hybridized Carbon III: Substitution and Elimination Reactions of Compounds with Leaving Groups Other Than Halogen. Organometallic Compounds.
Substitution Reactions of Alcohols. Additional Methods for Converting Alcohols into Alkyl Halides. Conversion of Alcohols into Sulfonate Esters. Dehydration of Alcohols. Substitution Reactions of Ethers. Reactions of Epoxides. Arene Oxides. Organometallic Compounds. Crown Ethers. Thiols, Sulfides, and Sulfonium Salts. Reactions of Quaternary Ammonium Compounds. Phase Transfer Catalysis.
IV. IDENTIFICATION OF ORGANIC COMPOUNDS.
12. Mass Spectrometry, Infrared Spectroscopy, and Ultraviolet/Visible Spectroscopy.
Mass Spectrometry. The Mass Spectrum. Fragmentation. Isotopes in Mass Spectrometry. Determination of Molecular Formulas: High-Resolution Mass Spectrometry. Fragmentation at Functional Groups. Spectroscopy and the Electromagnetic Spectrum. Infrared Spectroscopy. Infrared Absorption Bands. Intensity of Absorption Bands. Position of Absorption Bands. C—H Absorption Bands. Shape of Absorption Bands. Absence of Absorption Bands. Infrared Inactive Vibrations. Identifying Infrared Spectra. Ultraviolet and Visible Spectroscopy. The Beer-Lambert Law. Effect of Conjugation of
lmax. The Visible Spectrum and Color. Uses of UV/Vis Spectroscopy. 13. NMR Spectroscopy.
Introduction to NMR Spectroscopy. Fourier Transform NMR. Shielding. The Number of Signals in the 1H NMR Spectrum. The Chemical Shift. The Position of the 1H NMR Signals. Characteristic Values of Chemical Shifts. Integration of the NMR Signals. Diamagnetic Anisotropy. Splitting of the Signals. More Examples of 1H NMR Spectra. Coupling Constants. Splitting Diagrams. Time Dependence of NMR Spectroscopy. Protons Bonded to Oxygen and Nitrogen. Use of Deuterium in 1H NMR Spectroscopy. High Resolution 1H NMR Spectroscopy. 13C NMR Spectroscopy. DEPT 13C NMR Spectra. Two-Dimensional NMR Spectroscopy. Magnetic Resonance Imaging.
V. AROMATIC COMPOUNDS.
14. Aromaticity. Reactions of Benzene.
Criteria for Aromaticity. Aromatic and Nonaromatic Cyclic Hydrocarbons. Aromatic and Nonaromatic Heterocyclic Compounds. Some Chemical Consequences of Aromaticity. Antiaromaticity. A Molecular Orbital Description of Aromaticity and Antiaromaticity. Reactivity Considerations. General Mechanism for Electrophilic Aromatic Substitution Reactions. Halogenation of Benzene. Nitration of Benzene. Sulfonation of Benzene. Friedel-Crafts Acylation of Banzene. Friedel-Crafts Alkylation of Benene. Alkylation of Benzene by Acylation-Reduction. 15. Reactions of Substituted Benzenes.
Nomenclature of Subsitituted Benzenes. Reactions of Substituents on Benzene. The Effect of Substituents on Reactivity. The Effect of Substituents on Orientaiton. The Effect of Substituents on pKa. The Ortho/Para Ratio. Additional Consideration Regarding Substituent Effects. Designing a Synthesis III: Synthesis of Monosubstituted and Disubstitued Benzenes. Synthesis of Trisubstitued Benzenes. Synthesis of Substitued Benzenes Using Arenadiazonium Salts. The Arenadiazonium Ion as an Electrophile. Mechanism for the Reaction of Amines with Nitrous Acid. Nucleophilic Aromatic Substitution Reactions. Benzyne. Polycyclic Benzenoid Hydrocarbons. Electrophilic Substitution Reactions of Naphthalene and Substituted Naphthalenes.
VI. CARBONYL COMPOUNDS.
16. Carbonyl Compounds I: Reactions of Carboxylic Acids and Their Derivatives with Oxygen and Nitrogen Nucleophiles.
Nomenclature. Structures of Carboxylic Acids and Carboxylic Acid Derivatives. Physical Properties of Carbonyl Compounds. Reactivity Considerations. Relative Reactivities of Carboxylic Acids, Acyl Halids. Acid Anhydrides, Esters, and Amides. General Mechanism for Nucleophilic Acyl Substitution Reactions. Reactions of Acyl Halids. Reactions of Acid Anhydrides. Reactions of Esters. Acid-Catalyzed Ester Hydrolysis. Hydroxide-Ion-Promoted Ester Hydrolysis. Reactions of Carboxylic Acids. Reactions of Amides. Hydrolysis of Amides: Acid-Catalyzed Hydrolysis and Hydroxide-Ion-Promoted Hydrolysis. The Gabriel Synthesis of Primary Amines. Hydrolysis of Nitriles. Soaps, Detergents, and Micelles. Synthesis of Carboxylic Acid Derivatives. Dicarboxylic Acid Derivatives. 17. Carbonyl Compounds II: Reactions of Carbonyl Compounds with Carbon and Hydrogen Nucleophiles; Reactions of Aldehydes and Ketones with Oxygen and Nitrogen Nucleophiles; Reactions of a,
b-Unsaturated Carbonyl Compounds.
Nomenclature. Relative Reactivities of Carbonyl Compounds. Reactivity Considerations. Addition of Carbon Nucleophiles. Addition of Hydride Ion. Reactions of Carbonyl Compounds That Have Leaving Groups with Grignard Reagents and Hydride Ion Donors. Addition of Nitrogen Nucleophiles. Addition of Oxygen Nucleophiles. Protecting Groups. Addition of Sulfur Nucleophiles. The Wittig Reaction. Stereochemistry of Nucleophilic Addition Reactions: Re and Si Faces. Designing a Synthesis IV: The Synthesis of Cyclic Compounds. Nucleophilic Addition to
b-Unsaturated Aldehydes and Ketones: Direct Addition Versus Conjugate Addition. Nucleophilic Addition to
b-Unsaturated Carboxylic Acid Derivatives. Enzyme-Catalyzed Additions to
b-Unsaturated Carbonyl Compounds. 18. More about Oxidation-Reduction Reactions.
Reduction Reactions. Oxidation of Alcohols. Oxidation of Aldehydes and Ketones. Oxidation of Alkenes with Peroxyacids. Hydroxylation of Alkenes. Oxidative Cleavage of 1,2-Diols. Oxidative Cleavage of Alkenes: Ozonolysis. Oxidative Cleavage of Alkynes. Designing a Synthesis V: Functional Group Interconversion. Biological Oxidation-Reduction Reactions. Oxidation of Hydroquinones/Reduction of Quinones. 19. Carbonyl Compounds III: Reactions at the
a-Hydrogens. Keto-Enol Tautomerism. Reactivity Considerations. Halogenation of the
a-Carbon of Aldehydes and Ketones. Halogenation of the
a-Carbon of Carboxylic Acids: The Hell-Volhard-Zelinski Reaction.
a-Halogenated Carbonyl Compounds in Synthesis. Using Lithium Diisopropylamide (LDA) to Form an Enolate. Alkylation of the
a-Carbon of Carbonyl Compounds. Alkylation and Acylation of the
a-Carbon via an Enamine Intermediate. Alkylation of the
b-Carbon: The Michael Reaction. The Aldol Addition. Dehydration of Aldol Addition Products: Formation of
ab-Unsaturated Aldehydes and Ketones. The Mixed Aldol Addition. The Claisen Condensation. The Mixed Claisen Condensation. Intramolecular Condensation and Addition Reactions. Decarboxylation of 3-Oxocarboxylic Acids. The Malonic Ester Synthesis: Synthesis of Carboxylic Acids. The Acetoacetic Ester Synthesis: Synthesis of Methyl Ketones. Designing a Synthesis VI: Making New Carbon-Carbon Bonds. Reactions at the
a-Carbon in Biological Systems.
VII. BIOORGANIC COMPOUNDS.
Classification of Carbohydrates. The D and L Notation. Configuration of the Aldoses. Configurations of the Ketoses. Redox Reactions of Monosaccharides. Osazone Formation. Chain Elongation: The Kiliani-Fischer Synthesis. Chain Shortening: The Ruff Degradation. Stereochemistry of Glucose: The Fischer Proof. Cyclic Structure of Monosaccharides: Hemiactetal Formation. Stability of Glucose. Acylation and Alkylation of Monosaccharides. Formation of Glycosides. The Anomeric Effect. Reducing and Nonreducing Sugars. Determination of Ring Size. Disaccharides. Polysaccharides. Some Naturally Occurring Products Derived from Carbohydrates. Carbohydrates on Cell Surfaces. Synthetic Sweeteners. 21. Amino Acids, Peptides, and Proteins.
Classification and Nomenclature of Amino Acids. Configuration of Amino Acids. Acid-Base Properties of Amino Acids. The Isoelectric Point. Separation of Amino Acids. Resolution of Racemic Mixtures of Amino Acids. Peptide Bonds and Disulfide Bonds. Some Interesting Peptides. Strategy of Peptide Bond Synthesis: N-Protection and C-Activation. Automated Peptide Synthesis. Protein Structure. Determining the Primary Structure of a Protein. Secondary Structure of Proteins. Tertiary Structure of Proteins. Quaternary Structure of Proteins. Protein Denaturation. 22. Catalysis.
Catalysis in Organic Reactions. Nucleophilic Catalysis. Acid Catalysis. Base Catalysis. Metal-Ion Catalysis. Intramolecular Reactions. Intramolecular Catalysis. Catalysis in Biological Reactions. Enzyme-Catalyzed Reactions. Catalytic Antibodies and Artificial Enzymes. 23. The Organic Mechanisms of the Coenzymes. Metabolism.
Overall View of Metabolism. Niacin: The Vitamin Needed for Many Redox Reactions. Flavin Adenine Dinucleotide and Flavin Mononucleotide: Vitamin B2. Thiamine Pyrophosphate: Vitamin B1. Biotin: Vitamin H. Pyridoxal Phosphate: Vitamin B6. Coenzyme B12: Vitamin B12. Tetrahydrofolate: Folic Acid. Vitamin KH2: Vitamin K. 24. Lipids.
Fatty Acids. Waxes. Fats and Oils. Membranes. Prostaglandins. Terpenes. Vitamin A. Biosynthesis of Terpenes. Steroids. Biosynthesis of Cholesterol. Synthetic Steroids. 25. Nucleosides, Nucleotides, and Nucleic Acids.
Nucleosides and Nucleotides. ATP: The Carrier of Chemical Energy. Three Mechanisms for Phosphoryl Transfer Reactions. The “High-Energy” Character of Phosphoanhydride Bonds. Kinetic Stability of ATP in the Cell. Other Important Nucleotides. The Nucleic Acids. Helical Forms of DNA. Biosynthesis of DNA: Replication. Biosynthesis of Messenger RNA: Transcription. Ribosomal RNA. Transfer RNA. Biosynthesis of Proteins: Translation. Why DNA Contains Thymine Instead of Uracil. Determining the Base Sequence of DNA. Laboratory Synthesis of DAN Strands. Rational Drug Design.
VIII. SPECIAL TOPICS IN ORGANIC CHEMISTRY.
26. Synthetic Polymers.
General Classes of Synthetic Polymers. Chain-Growth Polymers. Stereochemistry of Polymerization. Ziegler-Natta Catalysts. Polymerization of Dienes. The Manufacture of Rubber. Copolymers. Step-Growth Polymers. Physical Properties of Polymers. Biodegradable Polymers. 27. Heterocyclic Compounds.
Saturated Heterocycles. Unsaturated Five-Membered-Ring Heterocycles. Unsaturated Six-Membered Ring Heterocycles. Biologically Important Heterocycles. 28. Pericyclic Reactions.
Three Kinds of Pericyclic Reactions. Molecular Orbitals and Orbital Symmetry. Electrocyclic Reactions. Cycloaddition Reactions. Sigmatropic Rearrangements. Pericyclic Reactions in Biological Systems. Summary of the Selection Rules for Pericyclic Reactions. 29. More about Multistep Organic Synthesis.
Functional Group Introduction, Removal. and Interconversion. More about Retrosynthetic Analysis: Disconnections. Retrosynthetic Analysis of Dioxygenated Compounds. More about Protecting Groups. Control of Stereochemistry. Selected Examples of Syntheses. 30. The Organic Chemistry of Drugs: Discovery and Design.
Naming Drugs. Lead Compounds. Molecular Modification. Random Screening. Serendipity in Drug Development. Receptors. Drugs and Enzyme Inhibitors. Designing a Suicide Substrate. Quantitative Structure-Activity Relationships (QSAR). Molecular Modeling. Combinatorial Organic Sysnthsis. Antiviral Drugs. Economics of Drugs. Governmental Regulations. Appendices.
Physical Properties of Organic Compounds. PKa Values. Derivations of Rate Laws. Summary of Methods Used to Synthesize a Particular Functional Group. Summary of Methods Used to Form Carbon-Carbon Bonds. Spectroscopy Tables.