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.