Exploring the amide coupling of carboxylic acids with amines using green solvent limonene

Abstract

Limonene was identified as green media for amide formation through quantum chemistry calculation. An environmentally benign and sustainable protocol for amide formation was developed with simple filtration without the need for extensive isolation and purification. Additionally, the scope and general compatibility of the proposed method were explored with aromatic and aliphatic substrates, giving moderate to excellent yields, and a gram-scale synthesis of SHP1 activator 3a-18 were easily performed for further biological evaluation.

Graphical Abstract

Keywords:

• Amides
• gram-scale
• limonene
• solvents
• theoretical calculations

Acknowledgments

The authors express their gratitude to facility support from the BioDuro-Sundia in Wuxi and high-performance computing cluster platform of the School of Biotechnology in Jiangnan University.

Additional information

Funding

This work was supported by National Natural Science Foundation of China [Nos. 22277043 and 21772068], Fundamental Research Funds for the Central Universities [JUSRP121065] and Postgraduate Research & Practice Innovation Program of Jiangsu Province [No. KYCX22_2330].