Hydrolysis of Unsymmetrical Acetamidines: Leaving Abilities and Stereoelectronic Effects

Article abstract of DOI:10.1021/ja00236a033

Unsymmetrical acetamidines hydrolyze in alkaline D2O to a mixture of two acetamides and two amines.Product ratios from three N-methylated acetamidines and five N-alkyl-N'-methylacetamidines were determined by NMR.The direction of cleavage is determined largely by the relative basicities of the two amines, rather than by the relative basicities of the two nitrogens in the tetrahedral intermediate.Steric repulsion in the product amides can also affect the product ratio, but only slightly.There is also a novel configurational effect, which favors cleavage of the nitrogen whose alkyl group is (Z) in the amidinium ion.This arises from a stereoelectronic preference for cleavage of a leaving group that is antiperiplanar to two lone pairs in the tetrahedral intermediate.However, it is concluded that this preference is weak.These results have guided the design of a test of this stereoelectronic preference in the hydrolysis of a set of cyclic amidinium ions where product stabilities and leaving abilities can be closely matched.