Decomposition of Pyridinyltriazenes in Aqueous Buffer: A Kinetic and Mechanistic Investigation

Article abstract of DOI:10.1021/jo00099a024

1-(X)-pyridinyl)-3-butyltriazenes (X-PBT), where X = 2,3, or 4, were prepared as prototypes of new chemotherapeutic agents.The acid-catalyzed decomposition of the 1-(X-pyridinyl)-3-butyltriazenes leads to the formation of the corresponding aminopyridines and butyl alcohols. pH-rate profiles, determined over a pH range of 3.5-12.00, show sigmoidal curves with slopes asymptotically approaching 0 at the extremes.The transitions have slopes where rate is inversely proportional to pH, indicating regions of acid catalysis.The solvent kinetic isotope effect, k_H2O/k_D2O, for each reaction is <1.0.The determination of the kinetics of the decomposition in amino buffers, ranging in pK_a from 8.95 to 10.4 and concentrations from 0.03 to 0.15 M, indicates negligible variation in the rate constants.These data strongly support the conclusion that the decomposition is specific acid catalyzed (A1) for each X-PBT isomer.This implies that the reactions involve fast, reversible protonation followed by the rate-determining heterolysis of the protonated species to the n-butyldiazonium ion and X-aminopyridine.Near neutral pH, the half-lives of the 2- and 4-isomers are ca. 100-fold shorter than that of the 3-isomer.This difference can be explained by protonation of the pyridinyl N, which leads to the direct dissociation only for the 2- and 4-isomers.Experimental pK_a''s were obtained for each isomer: 2-PBT, 5.19 +/- 0.19; 3-PBT, 4.89 +/- 0.12; 4-PBT, 7.77 +/- 0.16.These values are lower than, but follow the same order as, the pK_a values for the analogous isomers of aminopyridine.