Hydrazones and oximes are common conjugates, but are labile to hydrolysis. The hydrolytic stability of isostructural hydrazones and an oxime have been determined at pD 5.0-9.0. The hydrolysis of each adduct was catalyzed by acid. Rate constants for oxime hydrolysis were nearly 10 3 -fold lower than those for simple hydrazones; a trialkylhydrazonium ion (formed after condensation) was even more stable than the oxime. The data suggest a general mechanism for conjugate hydrolysis.
Keywordsconjugates; hydrazones; hydrolysis; oximes; reaction mechanisms Molecules containing carbon-nitrogen double bonds are prevalent in both chemical and biological contexts. The foundations for our current understanding of carbon-nitrogen doublebond formation and hydrolysis were laid by seminal early work on hydrazone hydrolysis and formation,[1] and by contributions from mechanistic studies on enzymes that utilize pyridoxal phosphate.[2] In particular, the meticulous kinetic analyses of Jencks resulted in the delineation of a carbinolamine intermediate in carbon-nitrogen double-bond formation and hydrolysis, and elucidation of the general mechanism of carbonyl-group addition reactions.[3,4] These principles were summarized in a landmark review. [5] Hydrazones and oximes (C 1 =N 1 −X 2 ) possess greater intrinsic hydrolytic stability than do imines. The textbook explanation for this greater stability invokes the participation of X 2 in electron delocalization (Figure 1).[6] The contribution of resonance form II in alkylhydrazones and oximes, and resonance form IV in acylhydrazones increases the negative-charge density