Abstract
Dimethyl sulfoxide (DMSO) effect on the alkaline hydrolysis rate of amide was studied. Among seven amides studied, i.e., benzamide, p-nitrobenzamide, N-methyl-p-nitrobenzamide, acetanilide, N-methylacetanilide, N, N-dimethylbenzamide and N, N-dimethyl-p-nitrobenzamide, DMSO increased the rates of the last two N, N-dimethylamides, and decreased the rates of the other five amides. Since DMSO increased the ester alkaline hydrolysis rates with desolvation of hydroxide ion, the rate determining step in N, N-dimethylbenzamides hydrolysis was assumed to be the OH- addition to carbonyl carbon as in ester. And in the other five amides, the rate determining step was assumed to be the leaving of amino group from the tetrahedral intermediate. This assumption was supported by pH dependence of DMSO effect on 2, 2, 2-trifluoro-N-methylacetanilide hydrolysis of which rate determining step depends on hydroxide ion concentration. From this standpoint, as DMSO decreased the hydrolysis rates of hexobarbital and thiamylal, the rate determining step of barbitals was considered to be C-N bond fission.
