Substituent effects on the mechanism changeover in a multi-pathway reaction: a model for the behavior of biological systems?

By studying the rearrangement in dioxane/water of a series of (Z)-arylhydrazones of 5-amino-3-benzoyl-1,2,4-oxadiazole (1a-k) into the relevant (2-aryl-5-phenyl-2H-1,2,3-triazol-4-yl) ureas (2a-k) in a wide range of pS(+) ( an operational scale of proton concentration in the mixed solvent used; dioxane/water, 1:1, v:v), the occurrence of three different reaction pathways (specific-acid-catalyzed, uncatalyzed, and general-base-catalyzed) for the relevant S(N)i process has been recently enlightened. The significantly different substituent effects on the three pathways cause some crossovers in the log k(A,R) versus pS(+) plots. Both the pS(+) value at which the crossover occurs and the width of the uncatalyzed pathway appear in turn substituent-dependent. Thus, thanks to the wide and complete range of substituents examined, the data obtained have been treated by using free-energy relationships. Interestingly enough, these results also furnish valuable information concerning the effects of "small" variations in chemical structures able to produce "large" reactivity variations in some way recalling what can occur in biological systems.