Malonic Ester Amide Synthesis: An Efficient Methodology for Synthesis of Amides

Abstract

A general methodology “malonic ester amide synthesis” has been demonstrated, which uses α-substituted/unsubstituted diethyl malonates for the decarboxylative acylation of various aromatic/heteroaromatic primary/secondary amines to form one-carbon homologated amides, thus providing easy access to amides with odd/even chain lengths and an array of substituents on the alkyl/aryl part while avoiding use of acyl chlorides or peptide coupling reagents.

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GRAPHICAL ABSTRACT

Keywords:

• Amide synthesis
• aromatic amines
• condensation
• decarboxylation
• diethyl malonates

ACKNOWLEDGMENTS

P. S. M. and J. P. M. thank the Council of Scientific and Industrial Research (CSIR), New Delhi, for the research fellowship. S. B. M. thanks the Department of Science and Technology (DST), New Delhi for the Ramanujan fellowship award and DST-Science and Engineering Research Council (SERC) Fast-Track project research grant. S. B. M. also thanks CSIR, New Delhi, and S. Pal, director, National Chemical Laboratory Pune, for providing the infrastructure, constant support, and encouragement.

Notes

^a Single step, 120 °C, 1 h (Cs₂CO₃ was not necessary, self-catalyzed).

^a α-Substituted DEM was purchased or prepared.^{[ 18 , 26–30 ]}

^b Step 1, 12 h. Step 2, 5 h.

^c Single step, 120 °C, 1 h (Cs₂CO₃ was not required, self-catalyzed).