Ester aminolysis in basic medium

Ester aminolysis, in general, occurs under harsh conditions that require high temperatures and extended reaction periods or the use of strong alkali metal catalysts. An efficient solid state synthesis of amides from nonenolizable esters and amines using KO Bu under the action of microwave irradiation [97] has been described. The reaction of esters with octylamine was extensively studied to identify possible micro-wave effects [98] (Eq. (45) and Tab. 3.20). 

The microwave-specific effect is increased when the reaction is performed in the absence of a phase transfer catalyst, showing that the nature of the reactive species is of great importance in connection with ionic dissociation (Eq. 46). 

As expected, the tighter ion pair (RNH , K+) exhibits the larger microwave effect. As an extension of this work, and in order to gain further insight, the effect of amine substituents was studied [99] in the reaction with ethyl benzoate (Eq. (47) and Tab. 3.21). 

The microwave effects are clearly substituent dependent and, as in the former example, disappear by adding a phase transfer agent. When the substituent R is able to delocalize the negative charge on the amide anion (R = Ph), the ion pairs RNH , M+ exist in a looser association. Consequently, a decrease in microwave effect is expected as the evolution from the GS - TS occurs with only a slight modification of polarity in the ion pairs. Conversely, the microwave effect is optimal with the tighter ion pair (nOctN , K+). 

In a parallel study [100], it was shown that formamide, primary and secondary amines react with esters in the presence of potassium terf-butoxide under the action of microwave irradiation. Substituted amides are formed in yields (generally more than 70%) much higher than under the action of conventional heating (Eq. (48) and Tab. 3.22). 

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