Organic Chemistry

Professor Michael B. Smith was born in Detroit, Michigan in 1946 and moved to Madison Heights, Virginia in 1957, where he attended high school at Amherst County High School. He received an A.A. from Ferrum College in 1967 and a B.S. in chemistry from Virginia Polytechnic Institute in 1969. After working for three years at the Newport News Shipbuilding and Dry Dock Co. in Newport News VA as an analytical chemist, he entered graduate school at Purdue University. He received a Ph.D. in Organic chemistry in 1977, under the auspices of Professor Joe Wolinsky. Professor Smith spent one year as a faculty research associate at the Arizona State University with Professor G. Robert Pettit, working on the isolation of cytotoxic principles from plants and sponges. He spent a second year of postdoctoral work with Professor Sidney M. Hecht at the Massachusetts Institute of Technology, working on the synthesis of bleomycin A2. Professor Smith began his academic career at the University of Connecticut in 1979, where he achieved the rank of professor of chemistry. In 1986 he spent a sabbatical leave in the laboratories of Professor Leon Ghosez, at the Université Catholique de Louvain in Louvain-la-Neuve, Belgium, as a visiting professor. He retired as a full professor from the University of Connecticut on January 1, 2017, and is currently pursuing his interests as an author.

Chapter 1: Introduction

1.1. A Brief History of Organic Chemistry

1.2. The Variety and Beauty of Organic Molecules

Chapter 2: Why Is an Acid-Base Theme Important?

2.1. Traditional Acid and Base Theory

2.2. There are Two Acid-Base Definitions: How Are They Related?

2.3. Acid-Base Equilibria and Equilibrium Constants

2.4. Electronegativity and Atom Size

2.4.A. Electronegativity

2.4. B. Atom Size

2.5. Atom Size and Electronegativity Arguments Applied to Acids and Bases

2.6. Resonance, Electron Dispersion and Base Strength

2.7. Lewis Acids and Bases

2.8. Why Is Acid–Base Chemistry a Theme for Organic Chemistry?

2.9. Biological Relevance

Correlation of Homework with Concepts

ANSWERS TO IN-CHAPTER QUESTIONS

HOMEWORK

Chapter 3: Bonding

3.1. Atomic orbitals and Electrons

3.1.A. Atomic Orbitals

3.1.B. Electronic Configuration

3.2. Ionic versus Covalent Chemical Bonds

3.3. Covalent Bonds

3.4. Linear Combination of Atomic Orbital (LCAO) Model

3.5. Tetrahedral Carbons and sp3 Hybridization

3.5.A. The Experimentally Determined Structure of Methane

3.5.B. Electron Promotion and sp3 Hybridization

3.5.C. The Hybrid Carbon Model of sp3-Hybrid Orbitals

3.6. The Valence Shell Electron Pair Repulsion (VSEPR) Model

3.7. Breaking Covalent Bonds

3.8. Carbon Bonded to Heteroatoms

3.8.A. A Covalent Bond Between Carbon and a Heteroatom: Bond Polarization

3.8.B. Bond Polarity, Bond Moments, and Bond Strength

Correlation of Homework with Concepts

ANSWERS TO IN-CHAPTER QUESTIONS

HOMEWORK

Chapter 4: Alkanes, Isomers, and an Introduction to Nomenclature

4.1. Alkanes

4.2. Structural Variations of Alkane Hydrocarbons

4.2.A. Straight-chain and Branched Alkanes

4.2.B. Isomers

4.3. The IUPAC Rules of Nomenclature

4.3.A. Prefixes and Simple Alkanes

4.3.B. Common Names

4.3.C. Halogens are Substituents

4.3.D. Multiple Substituents

4.3.E. Complex Substituents

4.4. Rings Made of Carbon: Cyclic Compounds

4.5. The Acid or Base Properties of Alkanes

4.6. Combustion Analysis and Empirical Formulas

4.7. Commercial and Biological Relevance

Correlation of Homework with Concepts

ANSWERS TO IN-CHAPTER QUESTIONS

HOMEWORK

Chapter 5: Functional Groups

5.1. -Bonds. The C=C Unit and Alkenes

5.2. -Bonds. The CºC Unit and Alkynes

5.3. Hydrocarbons With Several -Bonds

5.4. Terpenes

5.5. Heteroatom Functional Groups

5.5.A. Alcohols and Thiols

5.5.B. Ethers and Dithioethers (Sulfides)

5.5.C. Amines

5.6. Functional Groups With Polarized -Bonds

5.6.A. The Carbonyl Functional Group, C=O

5.6.B. Ketones and Aldehydes

5.6.C. Carboxylic Acids, Carboxylic Anions and Resonance

5.6.D. Double and Triple Bonds to Nitrogen

5.7. Acid-Base Properties of Functional Groups

5.8. Physical Properties and Intermolecular Forces

5.8.A. Boiling Point

5.8.B. Solubility

5.8.C. Melting Point

5.9. Benzene: A Special Cyclic Hydrocarbon

5.10. Biological Relevance

Correlation of Homework with Concepts

ANSWERS TO IN-CHAPTER QUESTIONS

HOMEWORK

Chapter 6: Acids, Bases, and Nucleophiles

6.1. Acid-Base Equilibria

6.2. Carboxylic Acids and Sulfonic Acids

6.2.A. Carboxylic Acids

6.2.B Sulfonic Acids

6.3. Factors That Influence the Strength of a Carboxylic Acid

6.3.A. Stability of the Conjugate Base

6.3.B. Inductive Effects

6.3.C. Solvent Effects

6.4. Alcohols Are Amphoteric

6.5. Amines

6.6. Carbon Acids

6.6.A. Terminal Alkynes Are Weak Acids

6.6.B. -Hydrogen Atoms and Carbonyls

6.7. Organic Bases

6.7.A. Amines

6.7.B. Alcohols Are Bases

6.7.C. Ethers Are Bases

6.7.D. Carbonyl Compounds Are Bases

6.7.E. Alkenes and Alkynes Are Bases

6.8. Lewis Acids and Bases

6.9. Nucleophiles

6.10. Biological Relevance

Correlation of Homework with Concepts

ANSWERS TO IN-CHAPTER QUESTIONS

HOMEWORK

Chapter 7. Chemical Reactions, Bond Energy, and Kinetics

7.1. A Chemical Reaction

7.2. Reactive Intermediates

7.2.A. Carbocations (Carbenium ions)

7.2.B. Carbanions

7.2.C. Radicals

7.3 Formal Charge

7.4. Free Energy: Enthalpy and Entropy

7.5. Bond Dissociation Enthalpy and Reactions

7.6. Transition States

7.7. Competing Reactions

7.8. Reversible Chemical Reactions

7.9. Reaction Curves and Intermediates

7.10. Mechanisms

7.11. Kinetics

7.11.A. Reaction Rate and First-Order Reactions

7.11.B. Second-Order Reactions

7.11.C. Half Life

7.11.D. No Reaction

7.12. Biological Relevance

Correlation of Homework with Concepts

ANSWERS TO IN-CHAPTER QUESTIONS

HOMEWORK

Chapter 8: Conformations

8.1. Rotation Around C—C Bonds

8.1.A. Staggered and Eclipsed Rotamers

8.1.B. Torsional Strain: Steric Hindrance and Energy Barriers

8.2. Longer Chain Alkanes

8.3. Influence of Heteroatoms on the Rotamer Population

8.3.A. Halogen Substituents

8.3.B. OH or NH Groups in Alcohols or Amines

8.4. Introducing -Bonds

8.5. Cyclic Alkanes

8.5.A. Strain and Steric Hindrance in Cyclic Alkanes

8.5.B. Conformations of C3–C5 Cycloalkanes

8.5.C. Conformationally Mobile Cyclohexane

8.6. Substituted Cyclohexanes. A1,3-Strain

8.7. Large Rings

8.8 Cyclic Alkenes

8.9. Biological Relevance

Correlation of Homework with Concepts

ANSWERS TO IN-CHAPTER QUESTIONS

HOMEWORK

Chapter 9: Stereoisomers: Chirality, Enantiomers, and Diastereomers

9.1. Stereogenic Carbons and Stereoisomers

9.2. Absolute Configuration [(R) and (S) Nomenclature]

9.3. Specific Rotation: A Physical Property

9.4. Circular Dichroism

9.5. Diastereomers

9.6. Alkenes

9.7. Cis and Trans Substituents Attached to Rings

9.8. Stereogenic Centers in Cyclic Molecules

9.9. Stereogenic Centers in Bicyclic Molecules

9.10. Optical Resolution

9.11. Biological Relevance

Correlation of Homework with Concepts

ANSWERS TO IN-CHAPTER QUESTIONS

HOMEWORK

Chapter 10: Acid–Base Reactions of -Bonds: Addition Reactions

10.1. Carbocation Stability

10.2. Alkenes React With Brønsted-Lowry Acids

10.3. Carbocation Rearrangements

10.4. Hydration Reactions of Alkenes

10.5. Alkenes React With Dihalogens

10.5.A Dihalogenation

10.5.B. Diastereoselectivity in the Dihalogenation Reaction of Alkenes

10.5.C. Reaction With Aqueous Solutions of Halogens (Hypohalous Acids)

10.6. Alkenes React With Borane

10.7. Alkenes React With Mercury(II) Compounds

10.8. Alkynes React as Bases

10.8.A. Reaction With Brønsted-Lowry Acids

10.8.B. Hydration of Alkynes

10.8.C. Dihalogenation of Alkynes

10.8.D. Hydroboration of Alkynes

10.8.E. Oxymercuration of Alkynes

10.9. Metathesis

10.10. Non-Ionic Reactions: Radical Reactions

10.11. Polymerization

10.12. Organization of Reaction Types

10.13. Biological Relevance

Correlation of Homework with Concepts

ANSWERS TO IN-CHAPTER QUESTIONS

HOMEWORK

Chapter 11: Substitution Reactions

11.1. Alkyl Halides, Sulfonate Esters, and the Electrophilic C—X Bond

11.2. The SN2 Reaction

11.2.A. Nucleophilic Approach to an Electrophilic Carbon

11.2.B. Reaction Rate and Energy Requirements

11.2.C. The Role of the Solvent

11.3. Functional Group Transformations Via the SN2 Reaction

11.4. The SN1 Reaction

11.5. Substitution Reactions of Alcohols

11.5.A. Alcohols React With Mineral Acids

11.5.B. Sulfur and Phosphorous Halide Reagents

11.5.C. Mitsunobu Reaction

11.6. Reactions of Ethers

11.6.A. Ethers React as Brønsted–Lowry Bases

11.6.B. Reactions of Epoxides

11.7. Free Radical Halogenation of Alkanes

11.8. C—H Substitution

11.9. Organization of Reaction Types

11.10. Biological Relevance

Correlation of Homework with Concepts

ANSWERS TO IN-CHAPTER QUESTIONS

HOMEWORK

Chapter 12: Elimination and p-Bond-Forming Reactions

12.1. Bimolecular Elimination

12.2. Stereochemical Consequences of the E2 Reaction

12.3. The E2 Reaction in Cyclic Molecules

12.4. Unimolecular Elimination: The E1 Reaction

12.5. Intramolecular Elimination

12.6. Elimination Reactions of Vinyl Halides: Formation of Alkynes

12.7. Substitution versus Elimination

12.8. Strength and Limitations of the Simplifying Assumptions

12.9. Organization of Reaction Types

12.10. Biological Relevance

Correlation of Homework with Concepts

ANSWERS TO IN-CHAPTER QUESTIONS

HOMEWORK

13: Spectroscopic Methods of Identification

13.1. Light and Energy

13.2. Mass Spectrometry

13.3. Infrared Spectroscopy

13.3.A. Absorbing Infrared Light and the Infrared Spectrophotometer

13.3.B. The Infrared Spectrum and Functional Group Absorptions

13.4. Nuclear Magnetic Resonance Spectroscopy

13.4.A. The Nuclear Magnetic Resonance Experiment

13.4.B. The Proton NMR Spectrum

13.5. Identifying Monofunctional Molecules

13.6. Carbon-13 NMR Spectroscopy: Counting the Carbons

13.7. Two-Dimensional (2D)-NMR

13.8. Biological Relevance

Correlation of Homework with Concepts

ANSWERS TO IN-CHAPTER QUESTIONS

HOMEWORK

Chapter 14: Organometallics

14.1. Organomagnesium Compounds

14.2. Grignard Reagents Are Bases and Nucleophiles

14.3. Organolithium Reagents

14.4. Organocuprates

14.5. Other Organometallic Compounds

14.6. Organization of Reaction Types

14.7. Biological Relevance

Correlation of Homework with Concepts

ANSWERS TO IN-CHAPTER QUESTIONS

HOMEWORK

Chapter 15: Oxidation

15.1. Defining an Oxidation

15.2. Oxidation of Alcohols

15.2.A. Chromium (VI) Oxidation of Alcohols

15.2.B. Swern Oxidation

15.3. Dihydroxylation of Alkenes

15.4. Epoxidation of Alkenes

15.5. Oxidative Cleavage

15.5. C—H Oxidation

15.6. Organization of Reaction Types

15.7. Biological Relevance

Correlation of Homework with Concepts

ANSWERS TO IN-CHAPTER QUESTIONS

HOMEWORK

Chapter 16: Reactions of Aldehydes and Ketones

16.1. Aldehydes and Ketones

16.2. The Reaction of Ketones and Aldehydes With Strong Nucleophiles

16.3. Stereoselectivity

16.4. The Reaction of Ketones and Aldehydes With Weak Nucleophiles

16.4.A. Reaction With Water

16.4.B. Reaction With Alcohols

16.4.C. Reaction With Amines

16.5. Organization of Reaction Types

16.6. Biological Relevance

Correlation of Homework with Concepts

ANSWERS TO IN-CHAPTER QUESTIONS

HOMEWORK

Chapter 17: Reduction

17.1 Defining a Reduction

17.2. Hydride Reducing Agents

17.3. Hydride Reduction of Other Functional Groups

17.4. Catalytic Hydrogenation

17.4.A. Hydrogenation of Alkenes and Alkynes

17.4.B. Homogeneous Hydrogenation

17.4.C. Hydrogenation of Heteroatom Functional Groups

17.5. Dissolving Metal Reductions

17.6. Organization of Reaction Types

17.7. Biological Relevance

Correlation of Homework with Concepts

ANSWERS TO IN-CHAPTER QUESTIONS

HOMEWORK

Chapter 18: Carboxylic Acid Derivatives and Acyl Substitution

18.1. Carboxylic Acids

18.2. Carboxylic Acid Derivatives: Structure and Nomenclature

18.3. Sulfonic Acids and Derivatives

18.4. Acyl Substitution and Hydrolysis of Carboxylic Acid Derivatives

18.5. Preparation of Acid Chlorides and Acid Anhydrides

18.6. Preparation of Esters

18.7. Baeyer-Villiger Oxidation

18.8. Preparation of Amides

18.9. Carboxylic Acid Derivatives React With Carbon Nucleophiles

18.10. Dicarboxylic Acid Derivatives

18.11. Nitrate Esters, Sulfate Esters, and Phosphate Esters

18.12. Nitriles Are Carboxylic Acid Derivatives

18.13. Fatty Acids and Lipids

18.14. Organization of Reaction Types

18.15. Biological Relevance

Correlation of Homework with Concepts

ANSWERS TO IN-CHAPTER QUESTIONS

HOMEWORK

Chapter 19: Aromatic Compounds and Benzene Derivatives

19.1. Benzene and Aromaticity

19.2. Functionalized Benzene Derivatives

19.2.A. Alkyl Substituents (Arenes)

19.2.B. Functional Groups on the Benzene Ring

19.3. Electrophilic Aromatic Substitution

19.3.A. Aromatic Substitution: Halogenation, Nitration, and Sulfonation

19.3.B. Friedel-Crafts Alkylation

19.3.C. Friedel-Crafts Acylation

19.4. Disubstituted Benzene Derivatives

19.4.A. Regioselectivity

19.4.B. Activating and Deactivating Substituents

19.4.C. Halogen Substituents

19.4.D. Aniline and Aniline Derivatives

19.5. Polysubstituted Benzene Derivatives

19.6. Aromatic Coupling Reactions

19.7. Reduction And Aromatic Compounds

19.8. Aromaticity in Monocyclic Molecules Other Than Benzene

19.9. Polynuclear Aromatic Hydrocarbons

19.9.A. Naphthalene, Anthracene, and Phenanthrene

19.9.B. Aromatic Substitution Reactions of Polycyclic Hydrocarbons

19.10. Nucleophilic Aromatic Substitution

19.11. Aromatic Amines and Diazonium Salts

19.12. Benzyne Intermediates

19.13. Synthesis of Aromatic Compounds

19.14. Spectroscopy of Aromatic Compounds

19.15. Organization of Reaction Types

19.16. Biological Relevance

Correlation of Homework with Concepts

ANSWERS TO IN-CHAPTER QUESTIONS

HOMEWORK

Chapter 20: Enolate Anions: Acyl Addition and Acyl Substitution

20.1. Aldehydes and Ketones Are Weak Acids

20.2. Non-nucleophilic Bases

20.3. Enolate Alkylation

20.4. The Aldol Condensation

20.5. The Zimmerman Model

20.6. The Intramolecular Aldol Condensation

20.7. Acid-Catalyzed Aldol Condensations

20.8. Ester Enolate Anions

20.8.A. Alkylation of Ester Enolate Anions

20.8.B. Acyl Substitution and Acyl Addition

20.8.C. Intramolecular Condensation: The Dieckmann Condensation

20.8.D. Malonic Ester Enolate Anions

20.9. Decarboxylation

20.10. The Knoevenagel Reaction, the Malonic Ester Synthesis,

and the Acetoacetic Acid Synthesis

20.11. Yid Reactions

20.12. Organization of Reaction Types

20.13. Biological Relevance

Correlation of Homework with Concepts

ANSWERS TO IN-CHAPTER QUESTIONS

HOMEWORK

Chapter 21: Difunctional Molecules: Dienes and Conjugated Carbonyl Compounds

21.1. Conjugation

21.2. Photochemistry of C=C and C=O

21.3. Detecting Conjugation With Ultraviolet Spectroscopy

21.4. Reactions of Conjugated -Bonds

21.5. Conjugate Addition

21.6. Reduction of Conjugated Systems

21.7. Organization of Reaction Types

21.8. Biological Relevance

Correlation of Homework with Concepts

ANSWERS TO IN-CHAPTER QUESTIONS

HOMEWORK

Chapter 22. Difunctional Molecules: Pericyclic Reactions

22.1. The Diels-Alder Reaction

22.2. Reactivity of Dienes and Alkenes

22.3. Selectivity in the Diels-Alder Reaction

22.4. Other Pericyclic Reactions: [3+2] [2+2]

22.5. Sigmatropic Rearrangements

22.6. Organization of Reaction Types

22.7. Biological Relevance

Correlation of Homework with Concepts

ANSWERS TO IN-CHAPTER QUESTIONS

HOMEWORK

Chapter 23: Heteroaromatic Compounds

23.1. Nitrogen, Oxygen and Sulfur in an Aromatic Ring

23.2. Substitution Reactions in Monocyclic Heterocyclic Aromatic Compounds

23.3. Heteroaromatic Compounds With More Than One Ring

23.4. Aromatic Substitution Reactions of Polycyclic Heterocycles

23.5. Reduced Heterocycles

23.6. Alkaloids

23.7. Biological Relevance

Correlation of Homework with Concepts

ANSWERS TO IN-CHAPTER QUESTIONS

HOMEWORK

Chapter 24: Multifunctional Compounds:

Amines, Amino Acids and Peptides

24.1. Reactions That Form Amines

24.2. Amino Acids

24.3. Reactions and Synthesis of -Amino Acids

24.4. Biological Relevance: Peptides

24.5. Biological Relevance: Proteins

24.6. Biological Relevance: Enzymes

24.7. Combinatorial Methods

24.8. Amino Acid Residue Identification in Proteins

24.9. End Group Analysis

24.10. Hormones

Correlation of Homework with Concepts

ANSWERS TO IN-CHAPTER QUESTIONS

HOMEWORK

Chapter 25: Multifunctional Compounds: Carbohydrates

25.1. Polyhydroxy Carbonyl Compounds

25.1.A. Monosaccharides

25.1.B. Hemi-Acetals

25.1.C. The Anomeric Effect

25.1.D. Ketose Monosaccharides

25.1.E. Amino Sugars

25.2. Disaccharides, Trisaccharides, Oligosaccharides, and Polysaccharides

25.3. Reactions of Carbohydrates

25.4. Glycosides

25.5. Biological Relevance: Nucleosides and Nucleotides

25.6. Biological Relevance: Polynucleotides

Correlation of Homework with Concepts

ANSWERS TO IN-CHAPTER QUESTIONS

HOMEWORK