This innovative book from acclaimed educator Paula Bruice is organized in a way that discourages rote memorization. The author's writing has been praised for anticipating readers' questions, and appeals to their need to learn visually and by solving problems. Emphasizing that learners should reason their way to solutions rather than memorize facts, Bruice encourages them to think about what they have learned previously and apply that knowledge in a new setting.KEY TOPICSThe book balances coverage of traditional topics with bioorganic chemistry, 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.For the study of organic chemistry.
(NOTE: Each chapter concludes with Key Terms, Problems, and a Summary.)
I. AN INTRODUCTION TO THE STUDY OF ORGANIC CHEMISTRY
1. Electronic Structure and Bonding—Acids and Bases.
The Structure of an Atom. The Distribution of Electrons in an Atom. Ionic, Covalent, and Polar Bonds. Representation of a Structure. Atomic Orbitals. An Introduction to Molecular Orbital Theory. Bonding in Methane and Ethane: Single Bonds. Bonding in Ethane: A Double Bond. Bonding in Ethyne: A Triple Bond. Bonding in the Methyl Cation, the Methyl Radical, and the Methyl Anion. Bonding in Water. Bonding in Ammonia and the Ammonium Ion. Bonding in the Hydrogen Halides. Summary: 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. Structures 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. Alkenes: Structure, Nomenclature, and an Introduction to Reactivity—Thermodynamics and Kinetics.
Molecular Formula and the Degree of Unsaturation. Nomenclature of Alkenes. The Structure of Alkenes. Cis- Trans Isomerism. The E,Z System of Nomenclature. How Alkenes React. Curved Arrows. Thermodynamics and Kinetics. 4. Reactions of Alkenes.
Addition of Hydrogen Halides. Carbocation Stability. The Structure of the Transition State. Regioselectivity of Electophilic Addition Reactions. Addition of Water and Addition of Alcohols. Rearrangement of Carbocations. Addition of Halogens. Oxymercuration-Reduction and Alkoxymercuration-Reduction. Addition of Borane: Hydroboration-Oxidation. Addition of Radicals. The Relative Stabilities of Radicals. Addition of Hydrogen. The Relative Stabilities of Alkenes. Reactions and Synthesis. 5. Stereochemistry: The Arrangement of Atoms in Space; The Stereochemistry of Addition Reactions.
Cis-Trans Isomers. Chirality. Asymmetric Carbon, Chirality Centers, and Stereocenters. Isomers with One Asymmetric Carbon. Drawing Enantiomers. Naming Enantiomers: The R, S System of Nomenclature. Optical Activity. Optical Purity and Enantiomeric Excess. Isomers with More Than One Asymmetric Carbon. Meso Compounds. The R, S System of Nomenclature for Isomers with More Than One Asymmetric Carbon. Reactions of Compounds that Contain an Asymmetric Carbon. The Absolute Configuration of (+)- Glyceraldehyde. Separating Enantiomers. Discrimination of Enantiomers by Biological Molecules. Enantiotopic Hydrogens, Diastereotopic Hydrogens, and Prochiral Carbons. Nitrogen and Phosphorus Asymmetric Carbons. Stereochemistry of Reactions: Regioselective, Stereoselective, and Stereospecific Reactions. Stereochemistry of Electrophilic Addition Reactions of Alkenes. Stereochemistry of Enzyme-Catalyzed Reactions. 6. Reactions of Alkynes—Introduction to Multistep Synthesis.
Nomenclature of Alkynes. Physical Properties of Unsaturated Hydrocarbons. The Structure of Alkynes. How Alkynes React. 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. 7. Electron Delocalization and Resonance—More About Molecular Orbital Theory.
Delocalized Electrons: the Structure of Benzene. The Bonding In Benzene. Resonance Contributors and the Resonance Hybrid. Drawing Resonance Contributors. Predicted Stabilites of Resonance Contributors. Resonance Energy. Stability of Allylic and Benzylic Cations. Stability of Allylic and Benzylic Radicals. Some Chemical Consequences of Electron Delocalization. The Effect of Electron Delocalization on pKa. A Molecular Orbital Description of Stability. 8. Reactions of Dienes—Ultraviolet/Visible Spectroscopy.
Nomenclature of Alkenes with More than One Functional Group. Configurational Isomers of Dienes. Relative Stabilities of Dienes. How Dienes React. Electrophilic Addition Reactions of Isolated Dienes. Electrophilic Addition Reactions of Conjugated Dienes. Thermodynamic Versus Kinetic Control of Reactions. The Diels-Alder Reaction: A 1,4-Addition Reaction. Ultraviolet and Visible Spectroscopy. The Beer-Lambert Law. Effect of Conjugation on Imax. The Visible Spectrum and Color. Uses of UV/VIS Spectroscopy.
III. SUBSTITUTION AND ELIMINATION REACTIONS.
9. Reactions of Alkanes: Radicals.
The Low Reactivity of Alkanes. 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. Reactions of Cyclic Compounds. Radicals Reactions in Biological Systems. Radicals and Stratospheric Ozone. 10. 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 Reaction. 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 SN1 and SN1 Reactions. Biological Methylating Reagents. 11. Elimination Reactions of Alkyl Halides; Competition Between Substitution and Elimination.
The E2 Reaction. The Regioselectivity of the E2 Reaction. 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.
IV. IDENTIFICATION OF ORGANIC COMPOUNDS.
12. Reactions of Alcohols, Ethers, Epoxides, and Sulfur-Containing Compounds—Organometallic Compounds.
Substitution Reactions of Alcohol. Amines Do Not Undergo Substitution Reactions. Other Methods Used to Convert Alcohols Into Alkyl Halides. Converting Alcohols into Sulfonates. Dehydration of Alcohols. Substitution Reactions of Ethers. Reactions of Epoxides. Arene Oxides. Crown Ethers. Thiols, Sulfides, and Sulfonium Salts. Organometallic Compounds. Coupling Reactions. 13. Mass Spectrometry and Infrared 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 on
lmax. The Visible Spectrum and Color. Uses of UV/Vis Spectroscopy. 14. NMR Spectroscopy.
Introduction to NMR Spectroscopy. Fourier Transform NMR. Shielding. The Number of Signals in the 1H NMR Spectrum. The Chemical Shift. The Relative Position of 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. Resolution of 1H NMR Spectra. 13C NMR Spectroscopy. DEPT 13C NMR Spectra. Two-Dimensional NMR Spectroscopy. Magnetic Resonance Imaging.
V. AROMATIC COMPOUNDS.
15. Aromaticity—Reactions of Benzene.
Criteria for Aromaticity. Aromatic Hydrocarbons. Aromatic Heterocyclic Compounds. Some Chemical Consequences of Aromaticity. Antiaromaticity. A Molecular Orbital Description of Aromaticity and Antiaromaticity. Nomenclature of Monosubstituted Benzenes. How Benzene Reacts. General Mechanism for Electrophilic Aromatic Substitution Reactions. Halogenation of Benzene. Nitration of Benzene. Sulfonation of Benzene. Friedel-Crafts Alkylation of Benzene. Friedel-Crafts Alkylations of Benzene. Alkylations of Benzene by Acylation-Reduction. 16. Reactions of Substituted Benzenes.
Nomenclature of Diubstituted and Polysubstituted Benzenes. Reactions of Substituents on Benzene. The Effect of Substituents on Reactivity. The Effect of Substituents on Orientation. The Effect of Substituents on pKa. The Ortho/Para Ratio. Additional Considerations Regarding Substituent Effects. Designing a Synthesis III: Synthesis of Monosubstituted and Disubstituted Benzenes. Synthesis of Trisubstituted Benzenes. Synthesis of Substituted Benzenes Using Arenediazonium Salts. The Arenediazonium 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.
17. Carbonyl Compounds I: Nucleophilic Acyl Substitution.
Nomenclature. Structures of Carboxylic Acids and Carboxylic Acid Derivatives. Physical Properties of Carbonyl Compounds. Naturally Occurring Carboxylic Acids and Carobxylic Acid Derivatives. How Class I Carbonyl Compounds React. Relative Reactivities of Carboxylic Acids, Acyl Halides, and Carboxylic Acid Derivatives. General Mechanism for Nucleophilic Acyl Substitution Reactions. Reactions of Acyl Halides. Reactions of Acid Anhydrides. Reactions of Esters. Acid-Catalyzed Ester Hydrolysis. Hydroxide-Ion-Promotes Ester Hydrolysis. Soaps, Detergents, and Micelles. Reactions of Carboxylic Acids. Reactions of Amides. Acid-Catalyzed Hydrolysis of Amides. Hydrolysis of an Imide- The Gabriel Synthesis. Hydrolysis of Nitriles. Designing a Synthesis IV: The Synthesis of Cyclic Compounds. Synthesis of Carboxylic Acid Derivatives. Dicarboxylic Acids and Their Derivatives. 18. Carbonyl Compounds II: Nucleophilic Acyl Addition, Nucleophilic Acyl Substitution, and Nucleophilic Addition-Elimination—Reactions of
b-Unsaturated Carbonyl Compounds.
Nomenclature. Relative Reactivities of Carbonyl Compounds. How Aldeyhdes and Ketones React. Reactions of Carbonyl Compounds with Carbon Nucleophiles. Reactions of Carbonyl Compounds with Hydride Ion. Reactions of Aldehydes and Ketones with Nitrogen Nucleophiles. Reactions of Aldehydes and Ketones with Oxygen Nucleophiles. Protecting Groups. Addition of Sulfur Nucleophiles. The Wittig Reaction. Stereochemistry of Nucleophilic Addition Reactions: Re and Si Faces. Designing a Synthesis V: The Synthesis of Cyclic Compounds. Nucleophilic Addition to -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. 19. Carbonyl Compounds III: Reactions at the
a-Hydrogens. Keto-Enol Tautomerism. How Enols and Enolate Ions React. 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 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
b-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.
20. 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 VII: Functional Group Interconversion. Biological Oxidation-Reduction Reactions. Oxidation of Hydroquinones/Reduction of Quinones. 21. More about Amines—Heterocyclic Compounds.
More About Nomenclature. More About Acid-Base Properties. Amine Inversion. Synthesis of Amines. Reactions of Amines. Reactions of Quaternary Ammonium Compounds. Phase-Transfer Catalysis. Unsaturated Five-Membered-Ring Heterocycles. Unsaturated Six-Membered-Ring Heterocycles. Biologically Important Heterocycles. 22. Carbohydrates.
Classification of Carbohydrates. The D and L Notation. Configurations 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: Hemiacetal 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. 23. 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. 24. 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. 25. 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.
VIII: SPECIAL TOPICS IN ORGANIC CHEMISTRY.
Fatty Acids. Waxes. Fats and Oils. Membranes. Prostaglandins. Terpenes. Vitamin A. Biosynthesis of Terpenes. Steroids. Biosynthesis of Cholesterol. Synthetic Steroids. 27. Nucleosides, Nucleotides, and Nucleic Acids I.
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 DNA Strands. Rational Drug Design. 28. 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. 29. 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. 30. The Organic Chemistry of Drugs: Discovery and Design.
Naming Drugs. Lead Compounds. Molecular Modification. Random Screening. Serendipity in Drug Development. Receptors. Drugs as Enzyme Inhibitors. Designing a Suicide Substrate. Quantitative Structure-Activity Relation-ships (QSAR). Molecular Modeling. Combinatorial Organic Synthesis. Antiviral Drugs. Economics of Drugs. Governmental Regulations. Appendices.
Physical Properties of Organic Compounds. 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. Answers to Selected Problems. Glossary. Photo Credits.
To the Instructor My guiding principle in writing this book was to create a text that focuses on the student, one that presents the material in a way that encourages students to think about what they have already learned and then apply this knowledge in a new setting. Some students look upon organic chemistry as a course they have to endure simply because it is part of their course of study. Others may get the impression that learning organic chemistry is akin to learning a foreign "language"--a diverse collection of molecules and reactions--the language of a country that they will never visit. I hope, however, that as students proceed through their study of organic chemistry, they see that it is a subject that unfolds and grows and allows them to use what they learn at the beginning of the course to predict what follows. Countering the impression that the study of organic chemistry necessarily involves simply memorizing molecules and reactions, this book revolves around shared features and unifying concepts, and it emphasizes principles that can be applied again and again. I want students to learn how to apply what they have learned to a new setting, reasoning their way to a solution, rather than memorizing a multitude of facts. I also want to encourage students to see that organic chemistry is integral to biology as well as to their daily lives. From the comments I have received from colleagues and students using previous editions, the book is working in the way I had hoped. As much as I enjoy having faculty tell me that their students are scoring higher than ever before on tests, nothing is more rewarding than hearing from the students themselves. Many students have generously attributed their success in organic chemistry to this book&3#51;not giving themselves nearly enough credit for how hard they studied to achieve that success. And they always seem surprised that they have come to love "orgo" (on the East Coast) or "o-chem" (on the West Coast). I also hear from many premedical students who say that the book gave them the permanent understanding of organic chemistry that allowed them to find the organic chemistry section of the MCAT to be the easiest part. In striving to make this fourth edition even more useful to students, I have relied on constructive comments from many of you. For these, I am extremely grateful. I also have kept a journal of questions that students asked when they came to my office. These questions let me know what sections in the book needed clarifying and what answers in theStudy Guide and Solutions Manualneeded more in-depth explanations. Most important, this analysis showed me where new problems could reduce the chance that students using the new edition would ask these same questions. Because I teach large classes, I have a vested interest in foreseeing potential confusion before it arises. In this edition, many sections have been rewritten to optimize readability and comprehension. A variety of new in-chapter and end-of-chapter problems will help students master organic chemistry through problem solving. There are also new interest boxes to show students the relevance of organic chemistry and there are additional margin notes to remind students of important concepts and principles. I hope you find the fourth edition even more appealing to your students. As always, I am eager to hear your comments--positive comments are the most fun, but critical comments are the most useful. A Functional Group Approach with a Mechanistic Organization That Ties Together Synthesis and Reactivity The organization of this book is designed to discourage rote memorization. The presentation of functional groups is organized around mechanistic similarities--electrophilic additions, radical substitutions, nucleophilic substitutions, eliminations, electrophilic aromatic substitutions, nucleophilic acyl substitutions, and nucle,ophilic addit