Foundations of Organic Chemistry Unity and Diversity of Structures, Pathways, and Reactions

Prologue

Acknowledgement

Part One: Background

Introduction

Chapter 1. An Introduction to Structure and Bonding.

A. The Sources of Carbon Compounds.

How Do We Know A Material is Pure?

B. More About Hydrocarbons Heats of Combustion and Reaction

C. On the Nature of the Chemical Bond.

I. Ionic and Nonpolar Covalent Bonds

II. Polar Covalent Bonds (Introduction to WebMO)III. Orbital Hybridization (Use of WebMO)IV Allotropes of Carbon

V Combinations of Ionic and Covalent Bonding

Notes and References

Problems

Chapter 2. An Introduction to Spectroscopy and Selected Spectroscopic Methods in Organic Chemistry

A. General Introduction. The Electromagnetic Spectrum

B. X-Ray Crystallography

C. Photon Spectroscopy

I. General Introduction

II. Ultraviolet and Visible Spectroscopy

III. Infrared Spectroscopy

IV. Raman Spectroscopy

V. Microwave Spectroscopy

VI. Magnetic Resonance Spectroscopy(a) Nuclear Magnetic Resonance (NMR)

1. The Chemical Shift

2. Multiplicity (The Coupling Constant - Spin-Spin Splitting)

3. The Integrated Area

4. Expansion of the Principle

5. NMR in Two Dimensions

6. Double Resonance

7. 13C, 19F and 31P NMR Spectroscopy

(b) Electron Spin Resonance (ESR)

D. Mass Spectrometry

I. Creation of Ions in the Mass Spectrometer

II. Separation of Ions by Mass

III. Detecting the Ions

Notes and References

Problems

Chapter 3, Structure: The Nomenclature of Hydrocarbons and the Shape of Things to ComeA. Introduction

B. Nomenclature and Spectroscopy

I. Alkanes in two and three dimensions

a Acyclic alkanes

b Cyclic alkanes

II. Alkenes, Arenes and Alkynes in two and three dimensionsa Alkenes

b Arenes

c Alkynes

C. Physical and Chemical Properties; Oxidation and Reduction of HydrocarbonsI. The Concept of Homology

II. Oxidation and Reduction

a Oxidation

b Reduction

Notes and References

Problems

Chapter 4, An Introduction to DynamicsA. Introduction

B. Review of Some Energy Considerations

C. The Barrier Between Reactants and Products

D. More About the Transition State

 E. Rotation About Sigma (σ) Bonds in Acyclic Alkanes, Alkenes, Alkynes and Alkyl Substituted Arenes

I. Alkanes

II. Alkenes, Alkynes and Alkyl Substituted Arenes

F. Conformational Analysis of Medium-Ring Cyclic Alkanes

G. The Conservation of Symmetry During Reactions

H. The Measurement of Chirality

I. The Wave Nature of Light

II Plane-Polarized Light and Handedness

III Optical Rotatory Dispersion (ORD and Circular Dichroism (CD)

Notes and References

Problems

Chapter 5. Classes of Organic Compounds - A Survey. An Introduction to Solvents, Acids and  Bases; More About Computational Chemistry

A. Introduction

B. General Characteristics of Functional Group Placement

C. The Functional Groups and Their Names and Some Physical and Spectroscopic Properties

 I. Hydrocarbons

a. Alkanesb. Alkenes

c. Alkynes

d. Arenes

II. Alkyl and Aryl Halides

III. Alcohols and Phenols

IV. Ethers

V. Thiols, Thioethers, Disulfides and their Oxides

VI. Amines, Hydrazines, and Other Nitrogenous Materials

VII. Phosphines, Phosphonium Salts and Other Phosphorus Derivatives

VIII. An Introduction to Organometallic Compounds

IX Compounds Containing Unsaturated Functional Groups

a. Aldehydes

b. Ketones

c. Nitrogen, Sulfur and Phosphorus Analogues of Aldehydes and Ketones

d. Carboxylic Acids

e. Carboxylic Acid Derivatives

1 Carboxylic acid halides (acyl halides)

2. Carboxylic acid anhydrides

3. Carboxylic Acid Esters and Lactones

4. Amides, Lactams, Imides, Hydroxamic Acids and Ureas5. Nitriles

D. An Introduction to Solvents

I. Protic and Aprotic Solvents

II. Polar and Nonpolar Solvents

III. Polarizability

IV Choosing a Solvent

a. Solvents for Spectroscopy

b. Immiscible Liquids

c. Organic Compounds that Dissolve in Water

d. Phase Transfer Catalysts

E. Acids and Bases

I. Brǿnsted Acids and Bases

II. Lewis Acids and Bases

III. Hard and Soft Acids and Bases

F. Computational Methods

Notes and References

Problems

Part Two: Middleground

Introduction

Chapter 6. Reactions of Hydrocarbons: Oxidation, Reduction, Substitution, Addition, Elimination and Rearrangement.

A. Introduction

B. Alkanes

I. Oxidation

II. Reduction

III. Substitution

IV. Rearrangement

C. Alkenes

I. Oxidation

II. Reduction

III. Addition

a. Electrophilic Addition

1. Stereochemistry of Electrophilic Addition

2. The Regiochemistry of Electrophilic Addition

3. The Kinetics of Electrophilic Addition

4. Cationic Polymerization

5. Electrophilic Addition to Dienes

6. Special Cases: Oxo and Ritter Reactions

b. Nucleophilic Addition to Alkenes, Dienes and Polyenes

c. Radical Addition to Alkenes, Dienes and Polyenes

d. Intermolecular Cheletropic and Other Cycloaddition Reactions

IV. Substitution

V. Rearrangements

D. Alkynes

I. Oxidation

II. Reduction

III. Addition

a. Electrophilic Addition

b. Nucleophilic Addition

c. Radical Addition to Alkynes

d. Intermolecular Cheletropic and Other Cycloaddition ReactionsE. Arenes and Aromaticity: Special Introduction

I. Oxidation

a. Oxidation of the Aromatic Ring

b. Oxidation of Alkyl Substituents on the Aromatic Ring

II. Reduction

III. Addition

IV. Substitution

a. Electrophilic Aromatic Substitution

b. Nucleophilic Aromatic Substitution

c. Free Radical Substitution

Notes and References

Problems

Chapter 7. The Reactions of Alkyl, Alkenyl and Aryl Halides: Oxidation, Reduction. Substitution, Addition, Elimination, and Rearrangement

A. Introduction

B. Fluorocarbons

I. Freons and Halons

II. Polymers of Highly Fluorinated Monomers

III. Use of Fluorocarbons to Carry Oxygen

C. Oxidation

D. Reduction of Alkyl, Alkenyl and Aryl Halides

I. Dehalogenation and Reduction at Carbon

a. Hydrogenolysis

b. Substitution of Hydride for Halide

c. Radical Replacement of Halogen by Hydrogen

d. Reaction of Alkyl, Alkenyl and Aryl Halides with Metals

1. Organomercurials

2. Organomagnesium Compounds (Grignard Reagents)

3. Alkyl, Alkenyl and Aryl Lithium Reagents

II. Reductions at Halogen

E. Nucleophilic Substitution

I. Nucleophiles and Nucleophilicity

II. Substitution, Nucleophilic, Unimolecular (SN1)

a. The Kinetics

b. Electronegativity Differences

c. The Structure of the Alkyl Group

d. The Role of the Solvent

e. Substrate Stereochemistry and the SN1

III. Substitution, Nucleophilic, Bimolecular (SN2)

a. The Kinetics

b. The Stereochemistry Attending the SN2

c. The Nature of the Leaving Group

d. The Nature of the Nucleophile

e. The Nature of the Solvent

IV. The SN2' Reaction

V. Nucleophilic Aromatic Substitution

a. The Elimination-Addition Pathway (Benzyne)

b. The Addition-Elimination Pathway (SNAr)

VI. Electrophilic Aromatic Substitution

VII. Substitution by Carbon

VIII. Photochemically Induced Substitution of Vinyl and Aryl Halides

F. Addition Reactions

I. Addition Reactions to Vinyl Halides

G. Elimination Reactions of Alkyl and Alkenyl Halides

I. α-Elimination (1,1-Elimination)

a. α-Elimination of HX

b. α-Elimination of X2

II β-Elimination (1,2-Elimination)

a. β-Elimination of HX

1. Elimination, Unimolecular (E1)2. Elimination, Unimolecular, Conjugate Base (E1cb)

3. Elimination, Bimolecular (E2)

4. 1,2-Elimination and the Primary Deuterium Isotope Effect

b. 1,2-Elimination of X2

III γ-Elimination (1,3-Elimination) and δ-Elimination (1,4-Elimination)

a. γ- Elimination of HX

b. γ- Elimination of X2

c. δ- Elimination of X2

H. Rearrangement Reactions of Alkyl and Alkenyl Halides

Notes and References

Problems

Chapter 8. Part One: The Reactions of Alcohols, Enols and Phenols: Oxidation   Reduction, Substitution, Addition Elimination, and Rearrangement  

 Part Two: Ethers.

 Part Three: Selected Reactions of Alkyl and Aryl Thiols and Thioethers.

Special Introduction

Part One: Alcohols, Enols and Phenols

A. Acidity and Basicity

B. Oxidation of Alcohols, Enols and Phenols

I. Introduction

II. Oxidation at the Hydroxyl Bearing Carbon

a. Chemical Oxidation of Alcohols

b. Biological Oxidation of Alcohols

III Oxidation at Sites that do not Bear the Hydroxyl

a. Oxidation of Enols

b. Oxidation of Phenols

c. Oxidation at the Double Bond of Allylic Alcohols

C. Reduction of Alcohols, Enols and Phenols

I Reduction of Alcohols

II Reduction of Enols and Phenols

D. Substitution Reactions of Alcohols, Enols and Phenols

I. Introduction

II. Substitution Reactions of Alcohols, Enols and Phenols at Oxygen

III. Substitution Reactions of Alcohols at Carbon

a. Formation of Alkyl Halides

b. Replacement of the Hydroxyl Group by Other Substituents

c. Replacement of the Hydroxyl (-OH) Functional Group by Carbon.

An Example from Nature.

 IV. Substitution Reactions of Enols and Phenols at Carbon.

 a. Substitution at the Carbon Bearing Oxygen.

b. Electrophilic Aromatic Substitution of Phenols

 E. Addition Reactions of Alcohols, Enols and Phenols

I. Introduction

II. Addition of the Oxygen of Alcohols to Carbon (with loss of Hydrogen).

F. Elimination Reactions of Alcohols, Enols and Phenols

I. Introduction

II. Acid Catalyzed Elimination of Water

III. Elimination from Derivatives of Alcohols

G. Rearrangement Reactions of Alcohols, Enols and Phenols

I. Introduction

Part Two: Ethers.

A. Introduction

B. The Reactions of Ethers

Part Three: Thiols, Thioethers, and Some Products of Their Oxidation.

Notes and References

Problems

Chapter 9. Part One.The Reactions of Aldehydes and Ketones: OxidationReduction, Substitution, Addition, Elimination, and Rearrangement  

Part Two. The Reactions of Carboxylic Acids and Their Derivatives:

Oxidation, Reduction, Substitution, Addition Elimination, and

Rearrangement

Introduction

Part One. Aldehydes and Ketones

A. Oxidation of Aldehydes and Ketones

B. Reduction of Aldehydes and Ketetones

I. Introduction

II. Reduction of Aldehydes and Ketones to Hydrocarbons

III. Reduction of Aldehydes and Ketones to Alcohols

C. Addition to Aldehydes and Ketones

I. Introduction

II. Photochemical Reactions of Aldehydes and Ketones

a. Nonconjugated Carbonyl Compounds

b. Conjugated Carbonyl Compounds

III. Thermal Electrocyclic and Related Reactions of Aldehydes and Ketones

a. Nonconjugated Carbonyl Compounds

b. Conjugated Carbonyl Compounds.

c. The Carbonyl "ene" ReactionIV. Nucleophilic Addition Reactions Retaining the Carbonyl Oxygen

a. General Comments

b. Addition of HX

c. Addition of Carbon Nucleophiles

1. Hydrogen Cyanide

2 . Organometallic Reagents.

3. The Aldol Reaction (Without Dehydration)

4. The Darzens Glycidic Ester Condensation

5. Epoxide Syntheses

6. The Benzoin Condensation

V. Nucleophilic Addition Reactions with Loss of the Carbonyl Oxygen

a. General Comments

b. Formation of Acetals, Ketals and Thioketals

c. Reaction of Aldehydes and Ketones with Nitrogen Nucleophiles

d. Replacement of the Carbonyl Oxygen by Halogen and Sulfur

e. Replacement of the Oxygen of the Carbonyl by Carbon.

f. Addition to the Carbon Alpha (α) to the Carbonyl.

1.Halogenation

 2..Alkylation

3. C-alkylation versus O-alkylation

4. Regioselectivity

5. Stereoselectivity

6. Eneamine Assisted Alkylation of Ketones.

D. Substitution Reactions Producing Aldehydes and Ketones.

I. Introduction

II. Reimer-Tiemann Synthesis

III. Gatterman-Koch (Friedel-Crafts) Formylation.

IV. The Pauson-Khand Reaction

E. Rearrangement Reactions of Aldehydes and Ketones

I. Introduction

II. The Benzilic Acid Rearrangement

III. The Dienone-Phenol Rearrangement.

IV. Anionic Rearrangements.

Part Two. Carboxylic Acids and Their Derivatives

 A. General Introduction.

 B. Oxidation

 C. Reduction.

 D. Substitution: Addition and Elimination

 E. Additional Reactions and Rearrangements of Esters and β-Dicarbonyl Compou¬nds

Notes and References

Problems

Chapter 10. Part One:The Reactions of Amines: Oxidation.Reduction, Addition, Substitution and Rearrangement.  

Part Two: Some Organophosphorus Chemistry.

Part Three:. Some Organosilicon Chemistry.

Part One The Reactions of Amines:

Introduction and Comments on the Synthesis of Amines

A. Oxidation of Amines

I. Oxygen and Peroxide Oxidation

II. Other Oxidizing Agents

a. General

b. Oxidation by Halogen

c. Oxidation with Nitrous Acid

B. Reduction of Amines

C. Addition and Substitution Reactions of Amines with a General Introduction

D. Addition and Rearrangement Reactions of Amines

Part Two: Some Organophosphorus Chemistry

Part Three. Some Organosilicon Chemistry

Notes and References

Problems

Part ThreeForeground

Introduction

Chapter 11 An Introduction to Carbohydrates, Acetogenins and Steroids

I. Introduction

II. The Calvin Cycle

III.Carbohydrates

A.Biosynthesis

B.Chemistry

C.Oligosaccharides

D.Polysaccharides

IV.Actetogenins

A. Acetyl Coenzyme A

B. Acetyl CoA to Fatty-Acids and Related Compounds

C. Isoprenoides: To Dimethylallyl Diphosphate and Beyond

1. Dimethylallyl Diphosphate from Acetyl Co A via Mevalonate

2. Dimethylallyl Diphosphate from Pyruvate and Glyceraldehyde

3. Terpenes

4. Loose Ends

i. Iridoids (Loganin and Secologanin)

ii. Shikimic acid, Isoshikimic acid and Prephenic acid

iii.The citric acid cycle (TCA, Krebs Cycle)

Notes and References

Problems

Chapter 12 An Introduction to Amino Acids, Peptides and Proteins, Enzymes, Coenzymes and Metabolic Processes.

I Introduction

II Amino Acids

A. Biosynthesis

B. Synthesis

III Peptides and Proteins

A. Amino Acids from Peptides

B. Peptides from Amino Acids -- in vivo

C. Peptides from Amino Acids -- in vitro

IV. The Coenzymes

A. Pyridoxal Phosphate

B. Lipoic Acid

C. Thiamin Diphosphate

1. 4-Amino-5-hydroxy-2-methylpyrimidine

2. 2-Methyl-5-(2-phosphonooxyethyl)thiazole

3. Thiamin Diphosphate

D. Biotin

E. Adenosine

F. Nicotinamide Adenine Dinucleotide (NAD+)

G. Coenzyme A (CoA-SH)

H. Flavin Adenine Dinucleotide (FAD)

I. S-Adenosylmethionine

J. Tetrahydrofolate

Notes and References

Chapter 13 An Introduction to Alkaloids and Some Other Heterocyclic Compounds Compounds

I. Introduction

II. Tropane Alkaloids A.Chemistry of Hyoscyamine

B. Chemistry of Nicotine

C. Biosynthesis of Hyoscyamine and Nicotine

1. The Common Feature

2. The Biosynthesis of Nicotine

3. The Biosynthesis of Hyoscyamine

4. The Biosynthesis of Tropic Acid

III. Morphine (and Codeine and Thebaine)

A. Chemistry of Morphine (and Codeine and Thebaine)

B. The Biosynthesis of Morphine (and Codeine and Thebaine)

C. The Synthesis of Morphine

IV. VinblastineA. Chemistry of Vinblastine

B. Biosynthesis of Vinblastine

V. Caffeine

A. Some History and the Synthesis of Caffeine

B. Biosynthesis of Caffeine

Notes and References

Chapter 14 Part One: On the Genetic Code: Unity and Diversity.  

Part Two: The Tetrapyrrolic Cofactors: Unity and Diversity.

Part One: Introduction

I. The Genetic Code

A. The Bases of Deoxyribonucleic Acid (DNA and Ribonucleic Acid (RNA)

1. Adenine (A)

2. Guanine (G)3. Uracil (U) and Thymine (T)

4.Cytosine (C)

B. Deoxynucleotides

C .The Role of Phosphate

D. The Sequencing of DNA

E. Chemical Synthesis of DNAF. Modification to DNA

1. Zinc Fingers

2. TALENs

3. CRISPR-Cas

Part Two: The Tetrapyrrolic Cofactors and other Metal Organic Frameworks (MOFs)

A. Introduction

B. Some Early Chemistry

C. Current Biosynthetic Understanding

Notes and References

Epilogue

Appendix I The Schrodinger Equation

Appendix II. The Literature