Table of contents

PREFACE

0.1 About the Textbook

0.2 How to Study with the Text

0.3 How to Study Organic Chemistry

CHAPTER 1. INTRODUCTION TO ORGANIC CHEMISTRY AND DRAWING MOLECULES

1.1 WHAT IS ORGANIC CHEMISTRY?

1.2 BOND-LINE STRUCTURES: ELECTRONS, BONDS, AND FORMAL CHARGES

1.2.1 Formal Charge

1.3 DEGREES OF UNSATURATION (DU)

1.3.1 Using DU for Molecules with Other Atoms

1.4 RESONANCE AND ELECTRON PUSHING

1.4.1 Moving Electrons without Violating Rules

1.4.2 Estimating the Relative Importance of Contributing Resonance Structures

1.5 X-RAY CRYSTALLOGRAPHY: FINDING POSITIONS OF ATOMS

            1.5.1 Why X-Rays?

1.5.2 The Spatially Periodic Crystalline State

1.5.3 How It’s Done

 

CHAPTER 2. MOLECULAR STRUCTURE - THE σ BOND

2.1 ATOMIC ORBITALS (AOs)

2.2 MOLECULAR ORBITALS (MOs)

2.2.1 H Atoms to Diatomic H2

2.2.2 AOs and MOs Define Atomic and Molecular Size

2.2.3 MO Energy Diagrams

2.2.4 Minimalist Summary of Bond Formation

2.3 HYBRIDIZATION OF AOs TO DETERMINE MOLECULAR SHAPE

2.3.1 Note to the Reader Regarding Sections 2.3, 2.6-2.8

2.3.2 Methane: The Simplest Stable Hydrocarbon

2.3.3 Hybridized Carbon AO Model for CH4

2.3.4 Shape of Hybrid Carbon Carbon sp3 AOs

2.3.5 Directionality of Hybrid MOs

2.3.6 Hybrid Carbon AOs + Hydrogen AOs --> CH4 MOs

2.3.7 Group sp3 Orbitals

2.4 PES: Evidence for CH4 MOs

2.5 CH4 ON THE MOVE

2.6 STRUCTURE OF THE METHYL ANION

2.6.1 MO Energy Diagram of the Methyl Anion

2.6.2 MOs of the Methyl Anion

2.7 STRUCTURE OF THE METHYL CATION

2.7.1 Directionality of Hybrid Carbon sp2 AOs

2.8 STRUCTURE OF THE METHYL RADICAL

2.8.1 The Improper Dihedral Angle

 

CHAPTER 3. MOLECULAR STRUCTURE – UNDERSTANDING σ and π BONDING

3.1 ATOMIC ORBITALS (AOs)

3.1.1 The Bond in Ethane Rotates

3.1.2 Molecules with Rotatable Bonds Related to Ethane

3.1.3 Naming Alkanes

3.2 STRUCTURE OF ETHYLENE: THE NON-ROTATABLE Π BOND

3.2.1 Molecules with Π Bonds Related to Ethylene

3.2.2 Namine Alkenes

3.3 PARALLEL MO INTERACTIONS IN GENERAL

3.3.1 Resonance Structures Involving Double Bonds

3.4 STRUCTURE OF ACETYLENE

3.4.1 MOs of Acetylene

3.4.2 Molecules with Π Bonds Related to Acetylene

3.5 CHEMISTRY AND BONDS

3.6 THE ALLYLIC ORBITAL SYSTEM

3.6.1 The Allyl Cation

3.6.2 The Allyl Anion

3.6.3 The Allyl Radical

3.6.4 Allylic MOs in Many Organic Molecules

3.7 BUTADIENE AND CONJUGATED Π BONDS

3.7.1 Shortcut to Building Conjugated Π MOs

3.8 LOCAL NATURE OF σ AND THE GLOBAL NATURE OF Π

3.8.1 Saturation Truncates Conjugated Systems

3.9 BOND AND ORBITAL HYBRIDIZATION UPON INSPECTION

3.10 INDUCTION, POLAR COVALENT BONDS, AND ELECTRONEGATIVITY

3.10.1 Dipole Moments and Molecular Polarity

3.10.2 The Magnitude of the Debye Unit

3.11 INTERMOLECULAR FORCES AND PHYSICAL PROPERTIES

3.11.1 Dispersion Forces

3.11.2 Dipole-Dipole Interactions

3.11.3 Hydrogen Bonding Interactions

3.12 UV-VIS SPECTROSCOPY – A MINIMAL INTRODUCTION

3.13 ANALYTICAL UV-VISIBLE SPECTRA AND MO CONJUGATION

3.13.1 The Electronic Transition

3.13.2 Protecting Yourself from Sunburn

3.13.3 Looking at UV-vis Spectra

3.13.4 Organic and Biological Analytical UV Spectroscopy

 

CHAPTER 4. ISOMERS

4.1 INTRODUCTION: SOURCES AND USES OF ALKANES

4.2 NOMENCLATURE

4.2.1 Naming Functional Groups

4.2.2 IUPAC Nomenclature

4.2.3 Molecules with Substituents Other than Carbon

4.2.4 Cyclic Molecules

4.2.5 Bicyclic Molecules

4.3 INFRARED SPECTROSCOPY

4.3.1 IR Spectra: Absorption Intensity

4.3.2 IR Spectra: Absorption Frequency

4.3.3 IR Spectra: Bond Strength

4.3.4 IR Spectra: Atomic Mass

4.3.5 IR Spectra: Absorption Band Width

4.3.6 IR Spectra: Coupled Frequencies

4.3.7 IR Spectra: Functional Group Identification

4.4 ISOMERS

            4.4.1 Stereoisomers / Enantiomers

4.4.2 Meso Compounds: Those that Posses an Internal Mirror of Symmetry

4.5 CHIRALITY AND NATURAL PRODUCTS

            4.5.1 R/S Configuration

4.6 CHIRAL COMPOUNDS THAT LACK A CHIRAL CENTER

4.7 OPTICAL ACTIVITY

4.7.1 Optical Purity

4.8 MULTIPLE CHIRAL ELEMENTS / DIASTEREOMERS

4.9 RESOLUTION OF ENANTIOMERS

4.9.1 Asymmetric Crystallization

4.9.2 Derivatization

4.9.3 Chromatography

4.9.4 Enzymatic Resolution

4.10 REVIEW OF STEREOISOMERS

 

CHAPTER 5. CHEMICAL REACTIVITY AND MECHANISMS

5.1 INTRODUCTION TO CHEMICAL THERMODYNAMICS

5.2 REACTION ENTHALPY (ΔHrxn)

5.3 REACTION ENTROPY

5.3.1 Entropy in Calorimetry

5.3.2 Changes in Chemical Entropy (ΔSrxn)

5.3.3 Universal Aspect of Entropy

5.4 GIBBS FREE ENERGY (ΔGrxn) FOR CHEMICAL EQUILIBRIA

5.4.1 ΔGrxn is a Difference in Entropy

5.4.2 Thermodynamic Parameters for Spontaneous Chemistry

5.4.3 Using ΔH of Chemical Bonds

5.5 EQUILIBRIA

5.5.1 ΔGrxn = –RTLn Keq

5.6 KINETICS

5.6.1 ΔG‡ is Not a State Function!

5.6.2 Molecular Features that Affect Reaction Rates

5.7 INTRODUCING ENERGY DIAGRAMS

5.7.1 Kinetic vs. Thermodynamic Products

5.8 READING ENERGY DIAGRAMS

5.9 CATALYSIS

5.10 USING pKa TO PREDICT HETEROLYTIC BOND FORMTAION

5.10.1 pKa is an Energy Unit

5.11 NUCLEOPHILES AND ELECTROPHILES

5.12 MECHANISMS AND ARROW PUSHING

5.13 ARROW PUSHING IN SPECIFIC REACTIONS

5.13.1 Heterolytic Bond Cleavage

5.13.2 Homolytic Bond Cleavage

5.13.3 Using Arrow Pushing in Mechanisms

 

CHAPTER 6. MOLECULAR CONFORMATION

6.1 INTRODUCTION TO MOLECULAR DYNAMICS

6.2 CONFORMATIONS OF OPEN-CHAIN NEWMAN PROJECTIONS

6.3 CONFORMATION IN CYCLIC MOLECULES

6.3.1 Conformation in Cyclohexanes

6.3.2 Drawing Cyclohexane Conformers

6.3.3 Axial / Equatorial vs. Cis / Trans

6.3.4 Chair Conformations

6.4 CYCLOHEXANE CONFORMATIONAL ENERGY

6.4.1 Relative Energies of Substituted Cyclohexanes

6.5 CHAIR CONFORMATIONS IN CYCLIC CARBOHYDRATES

6.6 CHAIR CONFORMATIONS IN SATURATED POLYCYCLIC STRUCTURES

6.7 NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY

6.7.1 Chemical Shifts in NMR

6.7.2 Chemical Shifts and Residual 1H in NMR Solvents

6.7.3 NMR Time Scale

6.7.4 NMR and Molecular Symmetry

6.7.5 NMR Integration and the Beer-Lambert Law

6.7.6 J-Coupling in NMR

6.7.7 Stepwise Analysis of First Order 1H NMR Coupling

6.7.8 Protic 1H NMR Chemical Shifts and Dynamic States

6.7.9 The NMR Time Scale

6.7.10 A Few More Notes about NMR Spectroscopy

6.8 13C NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY

6.8.1 Chemical Shifts in 13C NMR

 

CHAPTER 7. ONE-ELECTRON TRANSFER: RADICAL REACTIONS

7.1 INTRODUCTION TO RADICALS

            7.1.1 Radical Mechanisms

7.2 RADICAL STABILITY

7.3 CHLORINATION OF ETHANE

7.4 THERMODYNAMICS OF HALOGENATION

7.5 SELECTIVITY OF HALOGENATION

            7.5.1 Hammond’s Postulate

            7.5.2 Hammond’s Postulate in Selectivity of Halogenation

7.6 STEREOCHEMISTRY OF HALOGENATION

7.7 ALLYLIC / BENZYLIC BROMINATION

7.8 ATMOSPHERIC CHEMISTY AND THE OZONE LAYER

7.9 THE ORGANIC OXIDATION STATE

            7.9.1 Addition of Water or HX is Neither Oxidation Nor Reduction

7.10 AUTOOXIDATION

7.11 RADICAL ADDITION OF HBr

            7.11.1 Mechanism of Radical Addition to a C-C Pi Bond

            7.11.2 Reaction Conditions for Radical Addition of HBr

7.12 DISSOLVING METAL REDUCTION OF ALKYNES

7.13 BIRCH REDUCTION

7.14 RADICAL POLYMERIZATION

            7.14.1 Overview of a Radical Chain-Growth Polymerization Reaction

            7.14.2 Initiation

            7.14.3 Propagation

            7.14.4 Termination

            7.14.5 Kinetics

 

CHAPTER 8. ACIDS AND BASES

8.1 INTRODUCTION TO ACIDS AND BASES

8.2 BRØNSTED-LOWRY ACIDS AND BASES

8.2.1 Lewis Acids and Bases

            8.2.2 Curved Arrow Notation

8.3 ACIDITY

            8.3.1 Qualitative Perspective

            8.3.2 Quantitative Perspective

8.4 POSITION OF EQUILIBRIUM

8.5 BIOLOGICAL RELEVANCE

 

CHAPTER 9. SUBSTITUTION AND ELIMINATION REACTIONS

9.1 INTRODUCTION

9.2 KINETICS AND MECHANISMS

9.3 SUBSTITUTION REACTION MECHANISMS

            9.3.1 Bimolecular Substitution Reactions: SN2

9.3.2 Unimolecular Substitution Reactions: SN2

9.4 NUCLEOPHILES

            9.4.1 What is a Nucleophile?

            9.4.2 Protonation State

            9.4.3 Periodic Trends in Nucleophilicity

            9.4.4 Resonance Effects on Nucleophilicity

            9.4.5 Steric Effects on Nucleophilicity           

9.5 ELECTROPHILES AND CARBOCATION STABILITY

9.5.1 Steric Hindrance at the Electrophile

9.5.2 Carbocation Stability

9.6 LEAVING GROUPS

9.7 REGIOCHEMISTRY OF SN1 REACTIONS WITH ALLYLIC ELECTROPHILES

9.8 SN1 or SN2? PREDICTING THE MECHANISM

9.9 BIOLOGICAL NUCLEOPHILIC SUBSTITUTION REACTIONS

            9.9.1 A Biochemical SN2 Reaction

9.9.2 A Biochemical SN1 Reaction

9.9.2 A Biochemical SN1/2 Hybrid Reaction

9.10 NUCLEOPHILIC SUBSTITUTION IN THE ORGANIC SYNTHESIS LABORATORY

            9.10.1 Wiliamson Ether Synthesis

            9.10.2 Turning a Poor Leaving into a Good One: Tosylates

9.11 SUMMARY

 

CHAPTER 10. ELIMINATION REACTIONS

10.1 INTRODUCTION

10.2 UNIMOLECULAR ELIMINATION REACTION MECHANISM: E1

            10.2.1 Overview of the E1 Mechanism

10.2.2 Regiochemistry of E1 Elimination

10.2.3 Stereochemistry of E1 Elimination

10.4 BIMOLECULAR ELIMINATION REACTION MECHANISM: E2

10.4.1 Overview of the E2 Mechanism

10.4.2 Regiochemistry of E2 Elimination

10.4.3 Stereochemistry of E2 Elimination

10.5     COMPETITION BETWEEN ELIMINATION AND SUBSTITUTION REACTIONS

10.6     BIOCHEMICAL E1 ELIMINATION REACTIONS

10.7     SUMMARY