Kinetic Demonstration of the "Syn Effect" in β-Hydroxy Nitrosamine Fragmentation

Article abstract of DOI:10.1021/jo00146a004

The base-induced fragmentation rate of β-hydroxy nitrosamines is subject to striking control by the stereochemical orientation of the N-nitroso function. (Z)-(2-Hydroxy-2,2-diphenylethyl)methylnitrosamine (1Z) is cleaved to dimethylnitrosamine and benzophenone (k_obsd = 6.8x10^-3 s^-1) 287 times more rapidly than an equilibrium mixture of the Z and E isomers (13:87) at 35 deg C in tert-butyl alcohol containing potassium tert-butoxide.The rate constant for the fragmentation of the equilibrium mixture (k_obsd = 2.37x10^-5 s^-1) is similar in magnitude to the rateconstant (k_obsd = 1.67x10^-5 s^-1) for isomerization of the Z isomer (syn) to its E form.Arguments are presented in support of the hypothesis that the E isomer must isomerize prior to fragmentation.This remarkable stereoelectronic control of a C-C bond cleavage five bonds removed from the isomerizing N-NO group is attributed to the greater stability of the incipient syn α-nitrosamino carbanion.A Hammet study of substituent effects on the fragmentation rate of ring-substituted derivatives of 17 gives a ρ = -0.86, indicating modest positive charge development in the transition state.A detailed discussion of the mechanism is presented.