One-Pot Esterification and Amide Formation via Acid-Catalyzed Dehydration and Ritter Reactions

Abstract

Esterification of carboxylic acid is achieved using acetonitrile as a water trap. Water liberated during esterification is consumed in cyanide hydrolysis, thereby driving the esterification to completion. Substrates having carboxylic acid and nitrile groups undergo intramolecular dehydration and rehydration to amido esters in the absence of acetonitrile. Cyano acids also undergo esterification and Ritter reaction in one pot when excess alcohol is used. For the first time, we have observed an interesting Ritter reaction of primary alcohols, leading to ester amide product in one pot.

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GRAPHICAL ABSTRACT

Keywords:

• Amide
• dehydration
• esterification
• hydrolysis
• rehydration

ACKNOWLEDGMENTS

The authors thank the director of R. L. Fine Chemicals, Anjan K. Roy, for financial support, and K. R. Prabhu, Indian Institute of Science, for useful discussion.

Notes

^a Benzoic acid (81 mmol), alcohol (90 mmol), and acetonitrile (162 mmol) are used for the experiments.

^b Isolated yield. All reactions were carried out for 16–18 h.

^c In the absence of acetonitrile.

^a All the reactions were carried with 80 mmol of substrate, 90 mml of alcohol, and 162 mmol of acetonitrile with 94 mmol of sulfuric acid (98%) and yield referred to isolated yield.

^b Alcohol (180 mmol) used for the experiments.

^c 80 mmol of substrate, 190 mmol of alcohol, and 162 mmol of acetonitrile with 94 mmol of sulfuric acid (98%).

^d 80 mmol of substrate, 190 mmol of alcohol with 94 mmol of sulfuric acid (98%) and yield referred to isolated yield.

^a All the reactions were carried with 80 mmol of substrate, 360 mmol of alcohol, and 94 mmol of sulfuric acid (98%). Yield refers to isolated yield.