This article reviews the fundamentals of variational transition state theory (VTST), its recent theoretical development, and some modern applications. The theoretical methods reviewed here include multidimensional quantum mechanical tunneling, multistructural VTST (MS-VTST), multi-path VTST (MP-VTST), both reaction-path VTST (RP-VTST) and variable reaction coordinate VTST (VRC-VTST), system-specific quantum Rice–Ramsperger–Kassel theory (SS-QRRK) for predicting pressure-dependent rate constants, and VTST in the solid phase, liquid phase, and enzymes. We also provide some perspectives regarding the general applicability of VTST.

Variational transition state theory: theoretical framework and recent developments

Even though quantum mechanical tunnelling has been appearing recurrently mostly in theoretical studies that emphasize its decisive role for many chemical reactions, it still appears suspicious to most organic chemists. Recent experiments in combination with powerful computational approaches, however, have demonstrated that tunnelling must be included to fully understand chemical reactivity. Here we provide an overview of the importance of tunnelling in organic chemical reactions.

Tunnelling control of chemical reactions--the organic chemist's perspective.

A theoretical study of primary kinetic isotope effects (KIEs) is presented for proton transfer (PT) reactions in a polar environment in the nonadiabatic, i.e., tunneling, regime. This treatment differs from traditional descriptions for PT most notably in the identification of a solvent coordinate as the reaction coordinate. The theory explicitly addresses KIE features that are extremely sensitive to the proton donor−proton acceptor mode dynamics. Besides KIE behaviors that are not consistent with nontunneling PT, individual KIE aspects in some cases, such as magnitude, temperature dependence, variation with reaction asymmetry, and Swain−Schaad behavior can yield results consistent with nontunneling PT. However, a combination of KIE aspectswith particular emphasis on KIE variation with reaction asymmetry or temperaturecan clearly identify tunneling in PT systems. In addition, PT via excited proton vibrational states is shown to significantly contribute to the reaction rate and KIEs, especially for extremel...

Kinetic isotope effects for nonadiabatic proton transfer reactions in a polar environment. 1. Interpretation of tunneling kinetic isotopic effects

Publisher Summary This chapter focuses on the enolization of simple carbonyl compounds and related reactions. It presents an overview of the data on the tautomerism of simple carbonyl compounds. “Simple” designates compounds are those that lack enol-stabilizing functions accounting for a significant or great amount of enol. The chapter discusses the mechanism of keto-enol tautomerization and presents the results on stereochemical aspects of enolization (or enolate formation) and on regioselectivity when two enolization sites are in competition. Because the keto-enol equilibrium is so displaced toward the keto form that the enol concentration cannot usually be measured as a function of time, the keto–enol tautomerization cannot be studied directly for simple carbonyl compounds. Most kinetic studies have made use of the property that enolization is the rate-limiting stage of some stepwise reactions that have a rate corresponding to enolization or ionization itself. Enolization and ionization are also the first stages of some elimination reactions, such as aldolization and alkylation, but in most cases, the enolization (or ionization) process is not rate-limiting. Thermodynamic data on enol and enolate formation are needed to understand the kinetic behavior of these reactions; a complete picture must include data on the subsequent steps.

Enolisation of Simple Carbonyl Compounds and Related Reactions

Publisher Summary This chapter describes the use of dimethyl sulphoxide (DMSO) as an “inert” solvent in mechanistic investigations of heterolytic reactions and illustrates the methods developed for mechanistic study in dipolar aprotic media. The effect of DMSO on product distributions is discussed, and possible future uses of DMSO in mechanistic investigations are explained. The origin of the medium effect is considered, which is exhibited for reactions on changing from a hydroxylic solvent to a dipolar aprotic medium such as DMSO. The use of DMSO in organic chemistry has revealed the profound influence of solvent on the course and the rates of organic reactions but there is still a need to garner fundamental thermodynamic data relating to the transfer of solutes to DMSO from the aqueous state. Studies of simpler organic reactions in DMSO or its protic mixtures have revealed that this solvent can affect the outcome of a proton transfer process in a variety of ways. The stereochemical outcome of proton transfer can be retention, inversion, racemization, or a combination of these, depending on the presence or absence of DMSO. DMSO has unique molecular properties, which enable it to stabilize certain types of structures, such as the anionic intermediates in SNAR reactions. The two illustrative systems that are discussed to demonstrate the versality of this solvent in mechanistic studies are stabilization and catalytic decomposition of intermediates in SNAR reactions and the steric course of bimolecular Olefin-forming eliminations.

Physical Organic Chemistry of Reactions in Dimethyl Sulphoxide

An electrostatic charge-cloud model, including an empirical repulsive potential is used to calculate the properties of initial, final and transition states for the reaction X–H++ Yδ–→X–+ Yδ–H+, where X– and Yδ– are spherical charge distributions. The real and imaginary frequencies thus derived are used to calculate hydrogen isotope effects as a function of δ and hence of the energy change in the reaction. It is concluded that the observed variation of isotope effects cannot be accounted for in terms of the real vibrations of the transition state, but are primarily determined by the tunnel correction. The model also accounts for the dependence of isotope effects upon steric hindrance.

W. H. Sachs

Papers

Model calculations of isotope effects in proton transfer reactions