Kinetics and mechanism of hydrolysis of the amidinating agent, 1-(N 1-benzoylamidino)-3,5-dimethylpyrazole

Abstract

The kinetics of hydrolysis of 1-(N1-aroylamidino)-3,5-dimethylpyrazoles (3) have been studied at high and in 24·5% methanol at 30°. At high pH (>11) a specific base catalysed elimination occurs with the formation N-cyanoarenecarboxamides (which, stabilized as the anions, do not undergo further reaction) and 3,5-dimethylpyrazole. Variation of the N-aroyl substituent (in 1·0M-HO– in water) gave ρ=+0·45. In neutral solution is unreactive but acid hydrolysis results in direct formation of aroylureas. This reaction is specifically acid catalysed and the apparent pKa required to fit the kinetic data [1·40 in 24·5% methanol for the unsubstituted conmpound (3; X = H)] is the same as the measured spectrophotometric pKa. Data for the variation of the N-aroyl substituent are also presented and are consistent with a mechanism involving water attack on protonated (3). Kinetic data are also presented for N-benzoyl-S-methylisothiourea which also shows a rapid base-catalysed elimination (reflecting the improved leaving group, MeS–, relative to pyrazole anion) to give N-cyanobenzamide.