Synthesis of 2-Aminothiophenes Using Piperidinium Borate

Truly Catalytic Gewald Synthesis of 2-Aminothiophenes Using Piperidinium Borate (Pip Borate), a Conjugate Acid–Base Pair: K. D. Gavali, G. U. Chaturbhuj
SynOpen 2023, 7, 674–679

The Gewald reaction, first reported in 1960, is a one-pot cyclocondensation of ketones or aldehydes with activated nitriles and elemental sulfur to produce 2-aminothiophenes, which are important for synthesizing dyes, agrochemicals, and active pharmaceutical ingredients.

Boric acid is weak; thus, it can form a strong conjugate base, which can deprotonate active methylene compounds. Recently, the group of Professor Ganesh U. Chaturbhuj (Institute of Chemical Technology, Mumbai, India) described the first truly catalytic use of boric acid salts as conjugate acid–base pairs for a Gewald reaction, achieving excellent recyclability and reaction times ranging from 15 minutes to six hours with ethanol, or ethanol/water mixtures as eco-friendly solvents. The synthesis of tinoridine, NSAID, and analgesics was achieved under optimized conditions with excellent yields and short reaction times.

Professor Chaturbhuj said: “The current work depicts for the first time the use of a conjugate acid–base pair catalyst for the synthesis of 2-aminothiophenes via Gewald reaction with truly catalytic amounts with excellent yields of 19 products having outstanding recyclability and reusability of catalyst.”