Computational Organic Chemistry by Steven M. Bachrach

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Second Edition now available!

This web site serves as the companion to my book Computational Organic Chemistry, Second Edition published by Wiley. It provides access to supplementary materials for the book and to the ongoing blog.

The book provides a survey of examples where computational chemistry served to explicate problems in organic chemistry. The second edition inlcudes updates to the subjects covered in the first edition, along with a number of new studies, including two entirely new chapters. Details on the new materials in the second edition can be found in these blog posts.

Chapter 1. Quantum Mechanics for Organic Chemistry
- 1.1 Approximations to the Schrödinger Equation — the Hartree Fock Method
  - 1.1.1 Non-Relativistic Mechanics
  - 1.1.2 The Born Oppenheimer Approximation
  - 1.1.3 The One-Electron Wavefunction and the Hartree-Fock Method
  - 1.1.4 Linear Combination of Atomic Orbitals (LCAO) Approximation
  - 1.1.5 Hartree-Fock-Roothaan Procedure
  - 1.1.6 Restricted vs. Unrestricted Wavefunctions
  - 1.1.7 The Variational Principle
  - 1.1.8 Basis Sets
    - Basis Set Superposition Error
- 1.2 Electron Correlation — Post-Hartree-Fock Methods
  - 1.2.1 Configuration Interaction (CI)
  - 1.2.2 Size Consistency
  - 1.2.3 Perturbation Theory
  - 1.2.4 Coupled-Cluster Theory
  - 1.2.5 Multi-Configuration SCF (MCSCF) Theory and Complete Active Space SCF (CASSCF) Theory
  - 1.2.6 Composite Energy Methods
- 1.3 Density Functional Theory (DFT)
  - 1.3.1 The Exchange-Correlation Functionals: Climbing Jacob's Ladder
    - 1.3.1.1 Double Hybrid Functionals
  - 1.3.2 Dispersion-Corrected DFT
  - 1.3.3 Functional Selection
- 1.4 Computational Approaches to Solvation
  - 1.4.1 Microsolvation
  - 1.4.2 Implicit Solvation Models
  - 1.4.3 Hybrid Solvation Models
- 1.5 Hybrid QM/MM Methods
  - 1.5.1 Molecular Mechanics
  - 1.5.2 QM/MM Theory
  - 1.5.3 ONIOM
- 1.6 Potential Energy Surfaces
  - 1.6.1 Geometry Optimization
- 1.7 Population Analysis
  - 1.7.1 Orbital-based Population Methods
  - 1.7.2 Topological Electron Density Analysis
- 1.8 Interview: Stefan Grimme
- 1.9 References
Chapter 2. Computed Spectral Properties and Structure Identification
- 2.1 Computed Bond Lengths and Angles
- 2.2 IR Spectroscopy
- 2.3 Nuclear Magnetic Resonance
  - 2.3.1 General Considerations
  - 2.3.2 Scaling Chemical Shift Values
  - 2.3.3 Customized Density Functionals and Basis Sets
  - 2.3.4 Methods for Structure Prediction
  - 2.3.5 Statistical Approaches to Computed Chemical Shifts
  - 2.3.6 Computed Coupling Constants
  - 2.3.7 Case Studies
    - 2.3.7.1 Hexcyclinol
    - 2.3.7.2 Maitotoxin
    - 2.3.7.3 Vannusal B
    - 2.3.7.4 Conicasterol F
    - 2.3.7.5 1-Adamantyl Cation
- 2.4 Optical Rotation, Optical Rotatory Dispersion, Electronic Circular Dichroism, and Vibrational Circular Dichroism
  - 2.4.1 Case Studies
    - 2.4.1.1 Solvent Effect
    - 2.4.1.2 Chiral Solvent Imprinting
    - 2.4.1.3 Plumericin and Prismatomerin
    - 2.4.1.4 2,3-Hexadiene
    - 2.4.1.5 Multilayered Paracyclophane
    - 2.4.1.6 Optical Activity of an Octaphyrin
- 2.5 Interview: Jonathan Goodman
- 1.9 References
- 1.9 References
- 1.9 References
Chapter 3. Fundamentals of Organic Chemistry
- 3.1 Bond Dissociation Enthalpy
  - 3.1.1 Case Studies of BDE: Trends in the R-X BDE
- 3.2 Acidity
  - 3.2.1 Case Studies of Acidity
    - 3.2.1.1 Carbon Acidity of Strained Hydrocarbons
    - 3.2.1.2 Origin of the Acidity of Carboxylic Acids
    - 3.2.1.3 Acidity of Amino Acids
- 3.3 Isomerism and Problems With DFT
  - 3.3.1 Conformational Isomerism
  - 3.3.2 Conformations of Amino Acids
  - 3.3.3 Alkane Isomerism and DFT Errors
    - 3.3.3.1 Chemical Consequences of Dispersion
- 3.4 Ring Strain Energy
  - 3.4.1 RSE of Cyclopropane and Cylcobutane
- 3.5 Aromaticity
  - 3.5.1 Aromatic Stabilization Energy (ASE)
  - 3.5.2 Nucleus-Independent Chemical Shift (NICS)
  - 3.5.3 Case Studies of Aromatic Compounds
    - 3.5.3.1 [n]Annulenes
    - 3.5.3.2 The Mills-Nixon Effect
    - 3.5.3.3 Aromaticity Versus Strain
  - 3.5.4 π-π Stacking
- 3.6 Interview: Professor Paul Von Rague Schleyer
- 3.7 References
Chapter 4. Pericyclic Reactions
- 4.1 The Diels-Alder Reaction
  - 4.1.1 The Concerted Reaction of 1,3-Butadiene with Ethylene
  - 4.1.2 The Non-Concerted Reaction of 1,3-Butadiene with Ethylene
  - 4.1.3 Kinetic Isotope Effects and the Nature of the Diels-Alder Transition State
  - 4.1.4 Transition State Distortion Energy
- 4.2 The Cope Rearrangement
  - 4.2.1 Theoretical Considerations
  - 4.2.2 Computational Results
  - 4.2.3 Chameleons and Centaurs
- 4.3 The Bergman Cyclization
  - 4.3.1 Theoretical Considerations
  - 4.3.2 Activation and Reaction Energies of the Parent Bergman Cyclization
  - 4.3.3 The cd Criteria and Cyclic Enediynes
  - 4.3.4 Mayers-Saito and Schmittel Cyclization
- 4.4 Bispericyclic Reactions
- 4.5 Pseudopericyclic Reactions
- 4.6 Torquoselectivity
- 4.7 Interview: Professor Weston Thatcher Borden
- 4.8 References
Chapter 5. Diradicals and Carbenes
- 5.1 Methylene
  - 5.1.1 Theoretical Considerations of Methylene
  - 5.1.2 The H-C-H Angle in Triplet Methylene
  - 5.1.3 The Methylene Singlet-Triplet Energy Gap
- 5.2 Phenylnitrene and Phenylcarbene
  - 5.2.1 The Low-Lying States of Phenylnitrene and Phenylcarbene
  - 5.2.2 Ring Expansion of Phenylnitrene and Phenylcarbene
  - 5.2.3 Substituent Effects on the Rearrangement of Phenylnitrene
- 5.3 Tetramethyleneethane
  - 5.3.1 Theoretical Considerations of Tetramethyleneethane
  - 5.3.2 Is TME a Ground-State Singlet or Triplet?
- 5.4 Oxyallyl Diradical
- 5.5 Benzynes
  - 5.5.1 Theoretical Considerations of Benzyne
  - 5.5.2 Relative Energies of the Benzynes
  - 5.5.3 Structure of m-Benzyne
  - 5.5.4 The Singlet-Triplet Gap and Reactivity of the Benzynes
- 5.6 Tunneling of Carbenes
  - 5.6.1 Tunneling control
- 5.7 Interview: Professor Henry "Fritz" Schaefer
- 5.8 Interview: Professor Peter R. Schreiner
- 5.9 References
Chapter 6. Organic Reactions of Anions
- 6.1 Substitution Reactions
  - 6.1.1 The Gas Phase S_N2 Reaction
  - 6.1.2 Effect of Solvent on S_N2 Reactions
- 6.2 Asymmetric Induction via 1,2-Addition to Carbonyl Compounds
- 6.3 Asymmetric Organocatalysis of Aldol Reactions
  - 6.3.1 Mechanism of Amine-Catalyzed Intermolecular Aldol Reactions
  - 6.3.2 Mechanism of Proline-Catalyzed Intramolecular Aldol Reactions
  - 6.3.3 Comparison with the Mannich Reaction
  - 6.3.4 Catalysis of the Aldol Reaction in Water
  - 6.3.5 Another Organocatalysis Example: The Claisen Rearrangement
- 6.4 Interview - Professor Kendall N. Houk
- 6.5 References
Chapter 7. Solution-Phase Organic Chemistry
- 7.1 Aqueous Diels-Alder Reactions
- 7.2 Glucose
  - 7.2.1 Models Compounds: Ethylene Glycol and Glycerol
    - 7.2.1.1 Ethylene Glycol
    - 7.2.1.2 Glycerol
  - 7.2.2 Solvation Studies of Glucose
- 7.3 Nucleic Acids
  - 7.3.1 Nucleic Acid Bases
    - 7.3.1.1 Cytosine
    - 7.3.1.2 Guanine
    - 7.3.1.3 Adenine
    - 7.3.1.4 Uracil and Thymine
  - 7.3.2 Base Pairs
- 7.4 Amino Acids
- 7.5 Interview: Professor Christopher J. Cramer
- 7.6 References
Chapter 8. Organic Reaction Dynamics
- 8.1 A Brief Introduction to Molecular Dynamics Trajectory Computations
  - 8.1.1 Integrating the Equations of Motion
  - 8.1.2 Selecting the PES
  - 8.1.3 Initial Conditions
- 8.2 Statistical Kinetic Theories
- 8.3 Examples of Organic Reactions with Non-Statistical Dynamics
  - 8.3.1 [1,3]-Sigmatropic rearrangement of bicyclo[3.2.0]hex-2-ene
  - 8.3.2 Life in the Caldera: Concerted vs. Diradical Mechanisms
    - 8.3.2.1 Rearrangement of Vinylcyclopropane to Cyclopentane
    - 8.3.2.2 Bicyclo[3.1.0]hex-2-ene
    - 8.3.2.3 Cyclopropane Stereomutation
  - 8.3.3 Entrance into Intermediates from Above
    - 8.3.3.1 Deazetization of 2,3-Diazabicyclo[2.2.1]hept-2-ene
  - 8.3.4 Avoiding Local Minima
    - 8.3.4.1 Methyl Loss from Acetone Radical Cation
    - 8.3.4.2 Cope Rearrangement of 1,2,6-Heptatriene
    - 8.3.4.3 The S_N2 Reaction: HO^- + CH₃F
    - 8.3.4.4 Reaction of Fluoride with Formic Acid
  - 8.3.5 Bifurcating Surfaces: One TS, Two Products
    - 8.3.5.1 C₂-C₆ Enyne Allene Cyclization
    - 8.3.5.2 Cycloadditions Involving Ketenes
    - 8.3.5.3 Diels-Alder Reactions: Steps toward Predicting Dynamic Effects on Bifurcating Surfaces
  - 8.3.6 Stepwise Reaction on a Concerted Surface
    - 8.3.6.1 Rearrangement of Protonated Pinacolyl Alcohol
  - 8.3.7 Roaming Mechanism
  - 8.3.8 A Roundabout SN2 reaction
  - 8.3.9 Hydroboration: Dynamical or Statistical?
  - 8.3.10 A Look at the Wolff Rearrangement
- 8.4 Conclusions
- 8.5 Interview: Professor Daniel Singleton
- 8.6 References
Chapter 9. Computational Approaches to Understanding Enzymes
- 9.1 Models for Enzymatic Activity
- 9.2 Strategy for Computational Enzymology
  - 9.2.1 High Level QM/MM Computations of Enzymes
  - 9.2.2 Chorismate Mutase
  - 9.2.3 Catechol-O-Methyltransferase (COMT)
- 9.3 De Novo Design of Enzymes
- 9.4 References

Any book that hopes to capture the status of a dynamic field like computational chemistry is destined to become out-of-date. Even between the time the manuscript is completed and the book is printed and distributed, research continues on, and the book is by definition incomplete. This blog serves as a mechanism to update the book, providing brief posts commenting on recent articles that touch on or expand upon the subjects discussed in the printed book.

The book's auxiliary web site and blog extend the printed version into Web 2.0 space. On this auxiliary site, I have included all of the citations with links (using the DOI) to the cited articles, where electronic versions of those articles exist. Please keep in mind that most of these articles are not open-access and it is up to the reader to secure proper access rights to these articles. Also, most of the figures of 3-D molecules are reproduced along with their 3-D coordinates (as xyz files). These coordinates can be downloaded into your favorite molecular visualization tool for manipulation and re-use. All figures of 3-D molecules that have a border are actually links to the 3-D coordinates that will automatically load up into a Jmol applet, allowing you to manipulate the structure on-screen, in real time, within the blog window. Simply click on the figure to get this to work!

In addition, the blog provides an avenue for feedback from the readers. I welcome readers to comment on the book and the blog posts. I am particularly interested in correcting any errors that may be present in the book (or the blog).

Steven Bachrach
Trinity University

About the Book

Citations

Molecules

Second Edition now available!

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