On the Rearrangement in Dioxane/Water of (Z)-Arylhydrazones of 5-Amino-3-benzoyl-1,2,4-oxadiazole into (2-Aryl-5-phenyl-2H-1,2,3-triazol-4-yl)ureas:  Substituent Effects on the Different Reaction Pathways

Abstract

We have recently evidenced an interesting differential behavior in the reactivity in dioxane/water between the (Z)-2,4-dinitrophenylhydrazone (1a) and the (Z)-phenylhydrazone (1b) of 5-amino-3-benzoyl-1,2,4-oxadiazole. The former rearranges into the relevant triazole 2a only at pS+ > 4.5 while undergoing hydrolysis at high proton concentration (pS+ < 3.5); on the contrary, the latter rearranges into 2b in the whole pS+ range examined (0.1 < or = pS+ < or = 14.9). Thus, for a deeper understanding of these differences we have now collected kinetic data on the rearrangement in dioxane/water of a series of 3- or 4-substituted (Z)-phenylhydrazones (1c-l) of 5-amino-3-benzoyl-1,2,4-oxadiazole in a wide range of proton concentrations (pS+ 0.1-12.3) with the aim of gaining information about the effect of the substituent on the course of the reaction. All of the (Z)-arylhydrazones studied rearrange via three different reaction routes (specific-acid-catalyzed, uncatalyzed, and general-base-catalyzed), and the relevant results have been examined by means of free energy relationships.

On the use of multi-parameter free energy relationships: the rearrangement of (Z)-arylhydrazones of 5-amino-3-benzoyl-1,2,4-oxadiazole into (2-aryl-5-phenyl-2H-1,2,3-triazol-4-yl)ureas

“…Considering some our previous results 14,17,28 and because of their limited number and nature (in the instance of disubstituted (Z)-arylhydrazones only methyl substituents are present) we directly correlated reactivity data by using s þ values and by neglecting the proximity polar effect (its susceptibility constant was calculated near to zero) and obtained the results reported in line 2 of Table 3 again with an excellent correlation coefficient (R 2 >0.999).…”

“…'Classical' electronic, 'proximity polar', and 'primary steric' effects in MRH of (Z)-arylhydrazones of series c: a comparison with the reactivity of the relevant (Z)-arylhydrazones of series a (Z)-Arylhydrazones of series a (at C-5 a phenyl group is present) can rearrange via the general-base-catalyzed and the uncatalyzed pathways, 14,17 while those of series c (at C-5 an amino group is present) can rearrange also via the pS þ -dependent specific-acidcatalyzed pathway. 27,28 Thus the comparison between the effect of substituents in the MRH of (Z)-arylhydrazones of series a and c can be carried out for the first two pathways. To get initial information, we plotted the log k A,R (the logarithms of the rearrangement rate constants for the MRH) of compounds of series c versus those of the relevant ones of series a for both general-base-catalyzed and uncatalyzed paths (Fig.…”

“…Accordingly, an examination of the thermodynamic parameters concerning the rearrangement in the uncatalyzed pathway (for which the reactivity differences are higher and the discussion of thermodynamic parameters is 'correct'), 14,28 shows that the higher reactivity of (Z)-arylhydrazones of series c with respect to those of series a is essentially entropy-dependent (see after data under Section 2.3.2 and in Ref. 14).…”

“…Starting from the results of the IYT relationship applied to meta-and parasubstituted (Z)-arylhydrazones (19c, 20c, 22c, 24c, and 26e32c) 28 we have enlarged the FN treatment to all of the examined orthoand poly-substituted (Z)-arylhydrazones (1c, 3c, 4c, 8ce10c, 13c, 33c, 35ce38c), obtaining an excellent correlation (see line 3 of Table 3, R 2 >0.998).…”

“…Moreover by investigating the MRH of some meta-and parasubstituted (Z)-arylhydrazones of 5-amino-3-benzoyl-1,2,4-oxadiazole (19c, 20c, 22c, 24c, 26e32c) 28 we have gained a general FER-picture of meta-and para-substituents effects in the arylhydrazonic moiety on the different reaction pathways (general-basecatalyzed, uncatalyzed, and specific-acid-catalyzed).…”