Acylation. Part XXIX. The mechanism of ester aminolysis in non-hydroxylic media and the effect of nitrogen-containing leaving groups

Abstract

At 25° the aminolysis of p-nitrophenyl acetate and of various p,p′-disubstituted phenyl benzoates in diethyl ether solution obeys the rate equation –d[Ester]/dt=(k1[Ester][Amine]+k2[Ester][Amine]2). In acetonitrile solution this equation is simplified to –d[Ester]/dt=k1[Ester][Amine]. The aminolysis of esters of the form R1CO·O·NR22 obeys the rate equation –d[Ester]/dt=k1[Ester][Amine] in both ether and acetonitrile. The change of solvent has little effect on k1 for the latter esters, but k1 is notably increased in acetonitrile for the phenyl esters. The amines studied were n-butylamine, diethylamine, t-butylamine, and piperidine. The form of the rate equation is unchanged for the secondary amines, contrary to the findings of Shawali and Beichler for dioxan solutions. Steric effects affect both k1 and k2 and it is unlikely that the aminolysis of esters R1CO·O·NR22 are any more subject to these effects than are the phenyl esters. Under conditions of constant steric requirement the ratio k2 : k1 increases as electron withdrawing substituents are introduced into the acyl portion of phenyl benzoates. Substituent changes in the leaving group have a more complex effect on this ratio. In no case was there detectable catalysis of aminolysis by triethylamine. In ether all the esters were subject to catalysis by carboxylic acids, the N-containing compounds being particularly susceptible. In acetonitrile there is no detectable acid catalysis for the phenyl esters and that for the N-containing esters is greatly reduced.Rationalisation of the foregoing facts leads to aminolysis mechanisms resembling those we have previously established for acyl cyanides and ketens in non-hydroxylic solvents. The route employing two amine molecules involves a hydrogen-bonded, cyclic transition state. A cyclic, hydrogen-bonded transition state is also likely with the nitrogen-containing esters, as suggested by Young and co-workers. Shawali and Beichler's general conclusions about the mechanism of ester aminolysis cannot be sustained.