A Green Twist on the Ritter Reaction: Amide Synthesis in Lewis Acidic Deep Eutectic Solvents

Amides are chemically fundamental compounds with an extensive spectrum of applications in the material sciences, biology, medicine, and chemical synthesis1.The Ritter reaction, initially presented by John J. Ritter in 19482, is one of the many synthetic approaches that are accessible for the synthesis of amides. Conventionally, the Ritter reaction is counted on harsh reaction conditions like the use of strong acids (trifluoromethanesulfonic acid)3, noxious inorganic catalysts (CoCl2)4, toxic and volatile organic compounds (dichloroethane)5, reactive anhydrides (propylphosphonic anhydride)6, and high temperatures7 (Figure 1a). These factors not only produce safety risks but also conflict with the principles of green chemistry. In this communication, we present an innovative approach to produce amides by reacting secondary and tertiary alcohols with a variety of aliphatic and aromatic nitriles in Lewis acidic deep eutectic solvents (LADESs), which act as solvents and catalysts (Figure 1b). This method features mild (40 °C, 4h), aerobic conditions and yields up to 98% without chromatographic purification. Moreover, the efficiency of this methodology was demonstrated by the sustainable, multigram-scale synthesis of actoprotector Chlodantane8 (Figure 1c). CHEM21 metrics highlights its significantly reduced environmental impact, establishing this procedure as greener and more efficient substitute to traditional methods for the synthesis of amides9.