Synthesis of Amides from Esters and Amines

Synthesis of amides from the coupling reactions of esters and amines is a potentially attractive method however, stoichiometric amounts of promoters or metal mediators are normally required [52], Complex 8 also catalyzes the amide synthesis from esters and amines and the reaction is general and efficient, and proceeds under neutral conditions, thus providing an environmentally benign method [15]. As demonstrated in the alcohol acylation process (Section 1.3.3, Table 1.6), when symmetrical esters are used, acylation of amines occurs by both acyl and alkoxo parts of the esters and they are incorporated in the products, and the only byproduct generated from this reaction is H2. 

Entry Ester Amine Convet ion. of amine/time (%/h) Amides Isolated yields (%) 

When a benzene solution of complex 8 (0.1 mol%) containing pyrrolidine and ethyl acetate was refluxed under an argon atmosphere, quantitative conversion of pyrrolidine was observed by GC after 28 h, and N-acetylpyrrolidine was isolated in 98% yield (Table 1.10, entry 1). The same results were obtained when the reaction was carried out in refluxing toluene. The scope of the ester amidation reaction was explored with various esters and amines, and the results are summarized in Table 1.10. 

The aminolysis of esters catalyzed by complex 8 is possibly initiated by N-H activation of the amine by metal-ligand cooperation involving 8. Ester coordination followed by intramolecular nucleophilic attack by the amido ligand at the acyl functionality is thought to be a key step [15]. Overall, in one catalytic cycle, two 

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Table 1.10 Synthesis of amides from esters and amines catalyzed by complex...

Gnanaprakasam B, Milstein D (2011) Synthesis of amides from esters and amines with liberation of H2 under neutral conditions. J Am Chem Soc 133 1682... 

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