The role of nucleophilicity in the ratio of primary to secondary solute-derived products in the decomposition of (1-acetoxypropyl)propylnitrosamine.

The reactions of 1-propanediazotic acid, generated in situ from the hydrolysis of (1-acetoxypropyl)propylnitrosamine (1-APPN), with inorganic halides (X- = Cl-,Br-,I-) were studied in pH 8.0 buffer at 37 degrees C with specific emphasis on the extent of structurally rearranged solute-derived product. There is a direct correlation between the nucleophilicity of the halide and increased total and individual isomeric propyl halide (PrX) products. However, the relative formation of rearranged secondary propyl halide (2-PrX) is inversely proportional to solute nucleophilicity. The extent of isomerization ranges from 28% for Cl- to 13% for I-. In contrast, 2-propanol accounts for 33% of the total solvent-derived propanol yield. It is also demonstrated that the ratio of 1-PrX/2-PrX is inversely related to [X-] for Br- and I-. The data suggest that a nucleophilicity-driven association of the solute with a propanediazonium ion in the transition state leads to both primary and secondary products. The results are also discussed in terms of understanding the solvolysis products and DNA adducts previously observed from the metabolism of dipropylnitrosamine and the hydrolysis of N-propyl-N-nitrosourea.