On Sn2 reactions

The effects on SN2 reactions of the four variables—substrate structure, nucleophile, leaving group, and solvent—are summarized in the following statements and in the energy diagrams of Figure 11.7 ... 

Figure 11.7 Energy diagrams showing the effects of (a) substrate, (b) nucleophile, (c) leaving group, and (d) solvent on Sn2 reaction rates. Substrate and leaving group effects are felt primarily in the transition state. Nucleophile and solvent effects are felt primarily in the reactant ground state.

Huston, S. E., Rossky, P. J. and Zichi, D. A. Hydration effects on SN2 reaction An integral equation study of free energy surface and corrections to transitiion-state theory, J.Am.Chem.Soc., Ill (1989), 5680-5687... 

This example illustrates the synthesis of cyclic compounds by intramolecular alkylation reactions. The relative rates of cyclization for ca-haloalkyl malonate esters are 650,000 1 6500 5 for formation of three-, four-, five-, and six-membered rings, respectively.28 (See Section 3.9 of Part A to review the effect of ring size on Sn2 reactions.)... 

One of the earlier examples was reported on Sn2 reactions. Basilevsky reported more than two decades ago quantum-dynamical evidence that SN2 reactions of CH3F with nucleophiles X- were direct without trapping in the X CH3F pre-reaction complex.30... 

An example is the study by Lambert9 of the influence of aromatic rings and neighbouring electron-withdrawing groups on Sn2 reactions. He needed the few-tosylate 50. This comes from the diol 51 and now he had a choice. He could epoxidise an -alkene or dihydroxylate a Z-alkene. He chose the latter as Z-52 could be made by a Wittig reaction. 

Theoretical studies of the microsolvation effect on SN2 reactions have also been reported by our coworkers and ourselves (Gonzalez-Lafont et al. 1991 Truhlar et al. 1992 Tucker and Truhlar 1990 Zhao et al. 1991b, 1992). Two approaches were used for interfacing electronic structure calculations with variational transitional state theory (VST) and tunneling calculations. We analyzed both the detailed dynamics of microsolvation and also its macroscopic consequences (rate coefficient values and kinetic isotope effects and their temperature... 

Schowen (1972) used the Swain-Bader theory to explain solvent kinetic isotope effects on SN2 reactions involving halides, in terms of the numer of water molecules solvating a halide ion in the transition state (assumed to be three) vs. the number solvating it in the bulk (four). The contribution of a single halide-water hydrogen bond was also taken to depend on the partial charge on the halide, which could be consistent with either theory. 

In cases where steric factors are kept constant, electronic effects on Sn2 reactions can be observed however, these effects are found to be comparatively mail. Some 8 2 reactions are speeded up slightly by electron release, and others are speeded up slightly by electron withdrawal, but it is not usually possible to predict which will be the case simply from the structures involved... 

Parker and coworkers have investigated solvent effects on a variety of organic reactions. In one massive study on Sn2 reactions (Parker, et al., 1968), data are presented for a large number of substitution reactions carried out in a wide range of solvents. Data for two of the numerous... 

The accelerating effect of the carbonyl group on Sn2 reactions is demonstrated on p. 342 of the textbook. 

Scheme 8.69. The Chugaev reaction. The salt of an alcohol is allowed to react with carbon disulfide, producing the sodium salt of a dithiocarbonate derivative, which, on Sn2 reaction with methyl iodide (CH3I), produces the corresponding xanthate ester. Heating the xanthate (pyrolysis) results in loss of carbon oxysulfide (COS), methane thiol (thiomethane), and the corresponding alkene.

The rates of Sn2 reactions correlate well with relative nucleophilicities, because the nucleophile is intimately involved in the rate-determining step. In SnI reactions, the nucleophile is involved after the rate-determining step. Furthermore, the product ratios observed for Sn 1 reactions, when more than one nucleophile is present, do not correlate very well with relative nucleophilicities. This is because reactions with very unstable intermediates, such as carbenium ions, are not selective (see the reactivity-selectivity principle in Chapter 7). They occur at close to diffusion controlled rates. Therefore, in the following discussion, little needs to be said about the influence of the nucleophile on SnI reactions. Instead, our focus is on Sn2 reactions. 

Solvent effects on Sn2 reactions are common textbook material, but these reactions are not common in Nature. Nevertheless, there are a few... 

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