Nucleophilic Substitution on the Ultimate Hepatacarcinogen N-(Sulfonatooxy)-2-(acetylamino)fluorene by Aromatic Amines

Article abstract of DOI:10.1021/jo00030a043

The kinetics and products of the reactions of the title compound 1 with aniline (5) and N,N-dimethylaniline (6) were investigated in MeOH.Addition of 5 (0.1-0.4 M) to a solution of 1 in MeOD-d4 has no effect on the overall rate of decomposition of 1 but generates a number of adducts (20-24) in moderate to high yield.The yields of all solvolysis products, except the rearranged O-sulfates 18 and 19, are suppressed by the addition of 5.The kinetic and product data are consistent with an S_N1 mechanism (Scheme IV) in which 18 and 19 are generated by internal return from a tight ion pair, but all other products are generated by nucleophilic attack on a free nitrenium ion or solvent separated ion pair.The reaction of 6 with 1 shows similar characteristics to that of 5 with the exception that 6 reduces 1 in moderate yield to generate 2-(acetylamino)fluorene (25).This reduction occurs in competition with reaction to generate adducts (26, 27) similar to those obtained with 5.Kinetic and product data indicate that 25 is generated by reaction of 6 with a nitrenium ion intermediate.The differences in the behavior of 5 and 6 may be explained by cyclic voltammetry results which show that 6 is oxidized in MeOH more readily than 5 by about 2.5 kcal/mol.The reaction of 1 with 5 and 6 is considerably different from the rections of the same amines with the N-aryl-O-pivaloylhydroxylamines, which were previously shown to proceed via an S_N2 mechanism.This change in mechanism may be attributed, in part, to increased steric hindrance at the nitrogen of 1 due to the N-acetyl group.