Solvation, aliphatic nucleophilic substitution

In aliphatic nucleophilic substitution reactions, the solvation of the departing anions is particularly important. In protic solvents, this takes place mainly through hydrogen bonding, thus the activated complexes may be described as in Eqs. (5-100) and (5-101). 

Our study on the solvation to the TS of aliphatic nucleophilic substitution is now in its infancy, and the results are only preliminary. We hope that measurements of KIEs will also be effective in this study, as they were in our previous studies. 

This chain reaction is analogous to radical chain mechanisms for nucleophilic aliphatic nucleophilic substitution that had been suggested independently by Russell and by Komblum and their co-workers. The descriptive title SrnI (substitution radical-nucleophilic unimolecular) was suggested for this reaction by analogy to the SnI mechanism for aliphatic substitution. The lUPAC notation for the SrkjI reaction is (T -t- Dm -t- An), in which the symbol T refers to an electron transfer. When the reaction was carried out in Ihe presence of solvated electrons formed by adding potassium metal to the ammonia solution, virtually no aryne (rearranged) products were observed. Instead, reaction of 95c produced only 98 (40%) and 94 (40%) but no 99, and reaction of 96c produced 99 (54%) and 94 (30%) with only a trace of 98. ... 

Since charged species are often created or destroyed in nucleophilic substitution reactions, we can anticipate that solvent effects might be large. When examining the effect that the solvent can have on the rate of any reaction, it is important to compare the relative solvations of the reactants and the transition state. Differences in the solvation of the two affect the rate. In the case of nucleophilic aliphatic substitution, we need to compare the solvation of the alkyl-LG species and the separate nucleophile relative to the transition state. Often, the solvent itself is the nucleophile, and in these cases we are not as concerned with how it solvates itself. 

The trichloromethyl group of 4-(trichloromethyl)quinazoline can be replaced by methoxy, hydroxy, aliphatic amino, and pyrrolidino groups to give quinazolines 1. From a preparative point of view, these nucleophilic aromatic substitution reactions are similar to the replacement of other more common leaving groups. In the reaction of 4-(trichloromethyl)quinazoline with a methoxide ion, in contrast to the usual aromatic substitution mechanism, a covalent solvation adduct was isolated as intermediate. Whereas 4-(trichloromethyl)quinazoline prefers to undergo aromatic substitution, 4-(tribromomethyl)quinazoline prefers aliphatic substitution. 2-Methyl-4-(tribromomcthyl)quinazoline affords 2-methylquinazolin-4(3/f)-one in 74% yield on treatment with sodium hypobromite in dioxane, probably via an aromatic substitution reaction of a tribromomethyl group. 

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