Short, Efficient Syntheses of Pyrrole α-Amides

Abstract

We report an inexpensive method for producing a diverse array of pyrrole amides on a large scale and in good yield. The synthetic sequence allows for the preparation of a number of pyrrole amide derivatives in excellent to moderate yields from commercially available compounds. The diketene adduct, in the presence of an amine nucleophile, provides an excellent method for acetoacetylation. For diversity and versatility, a second method utilizing Meldrum's acid was successfully employed for the preparation of additional acetoacetamide derivatives. Using the Knorr pyrrole synthesis, pyrrole amides were readily prepared from the oxime of the acetoacetamides.

Keywords:

• Diketene
• Knorr pyrrole synthesis
• Meldrum's acid
• pyrrole amide
• synthesis

ACKNOWLEDGMENTS

M. T. H. thanks the American Chemical Society's Petroleum Research Fund (PRF 44304-GB4) and the University of West Florida (UWF) Research Foundation for their generous support of this work. P. S. B. was a Morelli-Quinteros Undergraduate Research Fellow. D. F. was a Project SEED summer I and II student at UWF and thanks the American Chemical Society for its support.

Notes

∗Reaction was conducted via one-pot reaction sequence.

∗∗Reaction failed give the desired product.