Experimental versus theoretical evidence for the rate-limiting steps in uncatalyzed and H+- and hydrolysis HO-- catalyzed of the amide bond

Abstract

Recent theoretical studies of the alkaline hydrolysis of the amide bond have indicated that the nucleophilic attack of the hydroxide ion at the carbonyl carbon of the amide group is rate limiting. This is shown to be inconsistent with a large amount of experimental observations where the expulsion of the leaving group has been shown to be rate limiting. A kinetic approach has been described, which allows us to diagnose whether the pH independent/uncatalyzed hydrolysis of amides involves (a) both the uncatalyzed water reaction(k W) andH+(kH) and HO--catalyzed (kOH) water reaction, (b) only the kW reaction, or (c) only the kH- + kOH reaction. The analysis described in this critical review does not favor the recent theoretical claims of the absence of the water reaction in the pH-independent/uncatalyzed hydrolysis of formamide and urea. copy;2009 Wiley Periodicals.