SN2 and Proton-Transfer Reactions

Sn2 reactions can be thought of as alkyl transfer reactions, and Sn2 characteristics can be anticipated by examining analogous proton transfer reactions. 

One after the other, step through (or animate) the sequence of structures depicting the SN2 and proton transfer reactions shown above. Compare the two. From what direction does cyanide approach the hydrogen in HCl From the same side as Cl ( frontside ), or from the other side ( backside ) Does the Sn2 reaction follow a similar trajectory  

Repeat the analysis for the Sn2 reaction. Is there significant buildup of positive charge on CH3  

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Reactions involving four electrons and three centres can include the formation of a chemical bond at the expenses of another bond which is consequently broken. A large variety of reactions can be explained by such a mechanism, by way of example attention here will be focused on bimolecular nucleophilic substitutions (Sn2) and proton transfers. Typically a four electron - three centre unit AXB, in which the central atom X could be a hydrogen or a carbon atom, is mainly described by the resonance of the following three classical VB structures... 

Many reactions can be described qualitatively by considering only three orbitals with four electrons. This includes proton transfer reactions (A - H + B-— A + H - B) and 8 2 reactions (X- Z + Y - X + Z- Y). The VB description of these reactions requires in principle the six states depicted in Fig. 2.7, which considered the typical case of the X + CH3-Y— X-CH3 + Y Sn2 reaction. 

In this article, we present an ab initio approach, suitable for condensed phase simulations, that combines Hartree-Fock molecular orbital theory and modem valence bond theory which is termed as MOVB to describe the potential energy surface (PES) for reactive systems. We first provide a briefreview of the block-localized wave function (BLW) method that is used to define diabatic electronic states. Then, the MOVB model is presented in association with combined QM/MM simulations. The method is demonstrated by model proton transfer reactions in the gas phase and solution as well as a model Sn2 reaction in water. 

The chloride exchange reaction in water is modeled in Monte Carlo simulations using the same approach as that described for the proton transfer reaction between ammonium ion and ammonia. The potential of mean force for the Sn2 reaction of C f + CH3C1 —> C1CH3 + C f obtained with the HF/6-31 G(d)... 

In CM terms the proton transfer reaction is very similar to the SN2 reaction of methyl derivatives. The two key configurations which are involved are the reactant and product configurations, [40] and [41]. The arguments that were applicable to methyl transfer reactions now may be utilized for proton transfer reactions. These may be summarized as follows ... 

An understanding of electron transfer and proton transfer is of great importance to the chemist, the first because it is concerned with a change in oxidation state and the second because to transform an organic compound it is usually necessary to disrupt the skin of hydrogen atoms that protect the compound. Equally familiar to the well-educated chemist are nucleophilic substitution reactions together with their SN1 and SN2 mechanisms. In recent 1 For the present addresses see p. v. 

Studies of proton transfers involving small ions with localized charge have shown that these reactions may proceed indeed with rate constants close to or even slightly larger than the collision rate constants predicted by the ADO theory (Mackay et al., 1976). However, rate-constant measurements of proton-transfer reactions between delocalized anions (Farneth and Brau-man, 1976) and sterically hindered pyridine bases (Jasinski and Brauman, 1980) and of SN2 displacement reactions (Olmstead and Brauman, 1977 Pellerite and Brauman, 1980 Pellerite and Brauman, 1983 Caldwell et al., 1984 for a review see Riveros et al., 1985) have shown that the rate constants can span the range from almost collision controlled values down to ones too slow to be observed. For these reactions the wide variation in rate constants has been explained on the basis of a double potential-well model which for a hypothetical SN2 substitution is schematically shown in Fig. 4. 

The mechanistic subtypes presented throughout this book include those related to the acid-base properties of organic molecules. These are protonations, deprotonations, and proton transfers. Mechanistic types based on solvation effects include solvolysis reactions, SN1, and El processes. Additional mechanisms utilizing ionic interactions include SN2, SN2, E2, 1,2-additions, 1,4-additions, and addition-elimination processes. Finally, those mechanistic types dependent upon the presence of cationic species include alkyl shifts and hydride shifts. 

Sodium hydroxide has been the most commonly used base in experimental nitroalkane proton transfer reaction studies.However, the computational studies of these reactions have generaUy been with hydroxide ion without the sodium counter ion. Recently a computational study of the proton transfer reactions of the three simple nitroalkanes in the presence of NaOH in water has been carried out and it was found that the presence of Na had an enormous effect on the energetics of the reactions. Double potential energy well diagrams, much like those found for the Sn2 reactions, were recorded for the proton transfer reactions of NM, NE and 2-NP with hydroxide ion in water. The computations included two explicit water molecules in the water cavity. The Gibbs free energies and enthalpies observed for the reactant complex (CPI), the TS and the product complex (CP2) both in the presence and absence of sodium ion and two explicit water molecules are summarized in Table 1.24. 

Proton transfer reactions such as the ones above are mechanistically identical to Sn2 reactions. By analogy with Sn2, identify the nucleophile, electrophilic atom, and leaving group for each. 

The first attempt to describe the dynamics of dissociative electron transfer started with the derivation from existing thermochemical data of the standard potential for the dissociative electron transfer reaction, rx r.+x-,12 14 with application of the Butler-Volmer law for electrochemical reactions12 and of the Marcus quadratic equation for a series of homogeneous reactions.1314 Application of the Marcus-Hush model to dissociative electron transfers had little basis in electron transfer theory (the same is true for applications to proton transfer or SN2 reactions). Thus, there was no real justification for the application of the Marcus equation and the contribution of bond breaking to the intrinsic barrier was not established. 

The modelling just deseribed of the direct HCl -1- CIONO2 reaction on an ice lattiee to produee molecular chlorine and ionized nitric acid portrayed a relatively faeile eoupled proton transfer/SN2 mechanism, evidently supported in subsequent ealeulations. These results also reinforced the idea of an ionic pathway involving ionized HC1,9-12,21 as opposed to molecular HC1. 

When CF3 is allowed to react with methyl benzoate, a new reaction channel appears along with the formation of the carbonyl addition product (Eq. 25). The nucleophile attacks at the methyl group to give an Sn2 substitution with the formation of the benzoate ion. In this case, proton transfer is not possible (no ot hydrogens), but benzoate is a better leaving group than acetate and substitution at the methyl group becomes viable. 

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