Reshaping Ritter reaction in Deep Eutectic Solvents: Sustainable Synthesis of Amides

Amides are fundamental compounds in chemistry, showcasing a vast spectrum of applications across biology, medicine, chemical synthesis, and material sciences. Among the numerous synthetic methodologies available, the Ritter reaction, first introduced by John J. Ritter in 1948, has emerged as one of the most significant and versatile approaches for the production of amides. Traditionally, the Ritter reaction has relied on harsh reaction conditions, including the use of strong acids (e.g., trifluoromethanesulfonic acid), harmful inorganic catalysts (e.g., CoCl₂), toxic and volatile organic solvents (e.g., dichloromethane), reactive anhydrides (e.g., propyl phosphonic anhydride), and high temperatures. These factors not only pose significant safety risks but also conflict with the principles of sustainable chemistry. In this communication, we present a green and efficient procedure for the synthesis of amides under mild and environmentally benign conditions. The process leverages Lewis acidic deep eutectic solvents (LADESs), which act simultaneously as catalysts and solvents. This innovative approach enables the transformation of secondary and tertiary alcohols into amides by reacting them with both aliphatic and aromatic nitriles. The method achieves excellent yields of up to 98%, under mild conditions (40 °C, 4 h), without requiring column chromatography for product purification.