Neighboring Group Effects in the β-Halo Amines. Synthesis and Solvolytic Reactivity of the anti-4-Substituted 2-Azaadamantyl System

Article abstract of DOI:10.1021/jo00337a026

The syntheses of anti-4-chloro-2-n-propyl-2-azaadamantane (1) and 2-(2-chloroethyl)-2-azaadamantane (8) were carried out.When 1 was subjected to solvolysis in aqueous methanolic NaOH, a rate enhancement of ca. 2*10⁶ was observed at 25 deg C, compared to that for 2-chloroadamantane (23).The solvolytic rate of 1 is comparable to that of an aliphatic β-halo amine, and because of the absence of a kinetic rate component due to solvent assistance in the adamantyl system, the observed enhancement may represent the rate-limiting case for the substituted β-chloroethylamines.The solvolysis rate of 8 was 2.5-fold less than that of 1, despite an expected decrease in activation energy.The lower rate for 8 may be due to its larger negative entropy of activation compared to that of 1.Indirect evidence was found for the existence of azridinium ion intermediates during solvolysis, but their direct observation remains to be accomplished.