Provides the background, tools, and models required to understand organic synthesis and plan chemical reactions more efficiently

Knowledge of physical chemistry is essential for achieving successful chemical reactions in organic chemistry. Chemists must be competent in a range of areas to understand organic synthesis. Organic Chemistry provides the methods, models, and tools necessary to fully comprehend organic reactions. Written by two internationally recognized experts in the field, this much-needed textbook fills a gap in current literature on physical organic chemistry.

Rigorous yet straightforward chapters first examine chemical equilibria, thermodynamics, reaction rates and mechanisms, and molecular orbital theory, providing readers with a strong foundation in physical organic chemistry. Subsequent chapters demonstrate various reactions involving organic, organometallic, and biochemical reactants and catalysts. Throughout the text, numerous questions and exercises, over 800 in total, help readers strengthen their comprehension of the subject and highlight key points of learning. The companion Organic Chemistry Workbook contains complete references and answers to every question in this text. A much-needed resource for students and working chemists alike, this text:

-Presents models that establish if a reaction is possible, estimate how long it will take, and determine its properties
-Describes reactions with broad practical value in synthesis and biology, such as C-C-coupling reactions, pericyclic reactions, and catalytic reactions
-Enables readers to plan chemical reactions more efficiently
-Features clear illustrations, figures, and tables
-With a Foreword by Nobel Prize Laureate Robert H. Grubbs


Organic Chemistry: Theory, Reactivity, and Mechanisms in Modern Synthesis is an ideal textbook for students and instructors of chemistry, and a valuable work of reference for organic chemists, physical chemists, and chemical engineers.

Professor Kendall Houk is Saul Winstein Professor at the UCLA. He is an authority on theoretical and computational organic chemistry. His group develops rules to understand reactivity, computationally models complex organic reactions, and experimentally tests the predictions of theory. He collaborates prodigiously with chemists all over the world. He has published nearly 1100 articles in refereed journals and is among the 100 most-cited chemists.

Professor Pierre Vogel is Professor of organic chemistry at the EPFL in Lausanne, Switzerland. He has published three books and has co-authored more than 490 publications in the fields of physical organic chemistry, organic and organometallic synthesis, total asymmetric synthesis of natural products of biological interest, catalysis, glycochemistry and bio-organic chemistry.

Das erfolgreiche Arbeiten mit organischen Reaktionen erfordert Wissen über Reaktivität, Reaktionsmechanismen, Thermodynamik und weitere Grundlagen der physikalisch-organischen Chemie. Das Lehrbuch vermittelt dieses Wissen. Auch erhältlich: das Arbeitsbuch zum Lehrbuch.

Preface xv

Foreword xxix

1 Equilibria and thermochemistry 1

1.1 Introduction 1

1.2 Equilibrium-free enthalpy: reaction-free energy or Gibbs energy 1

1.3 Heat of reaction and variation of the entropy of reaction (reaction entropy) 2

1.4 Statistical thermodynamics 4

1.4.1 Contributions from translation energy levels 5

1.4.2 Contributions from rotational energy levels 5

1.4.3 Contributions from vibrational energy levels 6

1.4.4 Entropy of reaction depends above all on the change of the number of molecules between products and reactants 7

1.4.5 Additions are favored thermodynamically on cooling, fragmentations on heating 7

1.5 Standard heats of formation 8

1.6 What do standard heats of formation tell us about chemical bonding and ground-state properties of organic compounds? 9

1.6.1 Effect of electronegativity on bond strength 10

1.6.2 Effects of electronegativity and of hyperconjugation 11

1.6.3 -Conjugation and hyperconjugation in carboxylic functions 12

1.6.4 Degree of chain branching and Markovnikov's rule 13

1.7 Standard heats of typical organic reactions 14

1.7.1 Standard heats of hydrogenation and hydrocarbation 14

1.7.2 Standard heats of CH oxidations 15

1.7.3 Relative stabilities of alkyl-substituted ethylenes 17

1.7.4 Effect of fluoro substituents on hydrocarbon stabilities 17

1.7.5 Storage of hydrogen in the form of formic acid 18

1.8 Ionization energies and electron affinities 20

1.9 Homolytic bond dissociations; heats of formation of radicals 22

1.9.1 Measurement of bond dissociation energies 22

1.9.2 Substituent effects on the relative stabilities of radicals 25

1.9.3 -Conjugation in benzyl, allyl, and propargyl radicals 25

1.10 Heterolytic bond dissociation enthalpies 28

1.10.1 Measurement of gas-phase heterolytic bond dissociation enthalpies 28

1.10.2 Thermochemistry of ions in the gas phase 29

1.10.3 Gas-phase acidities 30

1.11 Electron transfer equilibria 32

1.12 Heats of formation of neutral, transient compounds 32

1.12.1 Measurements of the heats of formation of carbenes 32

1.12.2 Measurements of the heats of formation of diradicals 33

1.12.3 Keto/enol tautomerism 33

1.12.4 Heat of formation of highly reactive cyclobutadiene 36

1.12.5 Estimate of heats of formation of diradicals 36

1.13 Electronegativity and absolute hardness 37

1.14 Chemical conversion and selectivity controlled by thermodynamics 40

1.14.1 Equilibrium shifts (Le Chatelier's principle in action) 40

1.14.2 Importance of chirality in biology and medicine 41

1.14.3 Resolution of racemates into enantiomers 43

1.14.4 Thermodynamically controlled deracemization 46

1.14.5 Self-disproportionation of enantiomers 48

1.15 Thermodynamic (equilibrium) isotopic effects 49

1.A Appendix, Table 1.A.1 to Table 1.A.24 53

References 92

2 Additivity rules for thermodynamic parameters and deviations 109

2.1 Introduction 109

2.2 Molecular groups 110

2.3 Determination of the standard group equivalents (group equivalents) 111

2.4 Determination of standard entropy increments 113

2.5 Steric effects 114

2.5.1 Gauche interactions: the preferred conformations of alkyl chains 114

2.5.2 (E)- vs. (Z)-alkenes and ortho-substitution in benzene derivatives 117

2.6 Ring strain and conformational flexibility of cyclic compounds 117

2.6.1 Cyclopropane and cyclobutane have nearly the same strain energy 118

2.6.2 Cyclopentane is a flexible cycloalkane 119

2.6.3 Conformational analysis of cyclohexane 119

2.6.4 Conformational analysis of cyclohexanones 121

2.6.5 Conformational analysis of cyclohexene 122

2.6.6 Medium-sized cycloalkanes 122

2.6.7 Conformations and ring strain in polycycloalkanes 124