OBSERVATION OF LARGE AMOUNTS OF C=0-18 EXCHANGE CONCURRENT WITH ACID-CATALYZED HYDROLYSIS OF TOLUAMIDES HAVING AMINE PORTIONS OF REDUCED BASICITY - THE INVOLVEMENT OF PROTONATED INTERMEDIATES IN THE ACID-CATALYZED HYDROLYSIS OF N-TOLUOYLPYRROLE

N-Toluoylpyrrole (2a) and N-toluoyl-2,5-dimethylpyrrole (2b) have been prepared along with their approximately 50% O-18-labeled analogues and the kinetics of hydrolysis and O-18-exchange studied in H3O+ at 72-degrees-C. N-Toluoylpyrrole shows a k(ex)/k(hyd) ratio of approximately 50 that is independent of [H3O+] between pH 0 and 1. Both k(ex) and k(hyd) are first order in [H3O+] in this range. The 2,5-dimethyl derivative (2b) exhibits an apparent reduction in k(ex)/k(hyd) of approximately 10(4) relative to 2a. While the hydrolysis of 2a is shown to proceed normally to produce pyrrole and toluic acid, hydrolysis of 2b is abnormal in that the initial products are toluamide and 2,5-hexanedione. Solvent kinetic isotope studies with 2a indicate a (k(ex))H/D value of 0.81 +/- 0.08 and (k(hyd))H/D value of 0.91 +/- 0.18. The large amount of O-18-exchange observed for 2a relative to that for benzamide, acetanilide, and N,2,4-trimethylacetanilide results from the low basicity of the pyrrole moiety which inhibits protonation and favors C-O cleavage. A generalized mechanism of acid-catalyzed hydrolysis for the above amides is presented.