Mechanochemical synthesis of coumarins via Pechmann condensation under solvent-free conditions: an easy access to coumarins and annulated pyrano[2,3-f] and [3,2-f]indoles

Abstract

A green protocol has been developed for the synthesis of simple coumarins and linear pyrano[2,3-f] and [3,2-f]indoles by the reaction of phenol derivatives with β-ketoesters under ball milling at ambient...

Recent developments in the solvent-free synthesis of heterocycles

“…In 2022, Ainur D. Sharapov et al reported solvent-free, mechanochemical coumarins synthesis by Pechmann condensation (Scheme 13). 26 They initiated the reaction using condensation between phloroglucinol 46a and ethyl acetoacetate 47a (molar ratio: 1 : 1.1) under acidic conditions. The ball-milling reaction was screened under several acid catalysts (TFA, TsOH, and MsOH) and the optimal conditions were established in the presence of 10 mol% methane sulfonic acid.…”

Batch and continuous flow mechanochemical synthesis of organic compounds including APIs

“…Colacino et al have further reported the mechanochemical synthesis of nitrofurantoin and dantrolene. 50 1-Aminohydantoin•HCl (41) was treated with aldehyde (42) in the absence of base and solvent to afford compound (43), selectively the E-isomer, and high yield (87-98%) with 10 examples within 10-15 min. Furthermore, they have extended their methodology for the synthesis of nitrofurantoin (44) and dantrolene (45), achieving an excellent yield (95% and 90%, respectively) after 2 h milling using a ball mill (Scheme 11).…”

Green metrics in mechanochemistry

“…Coumarine 59 synthesis by Pechmann condensation was recently revisited by Ranu team. 116 This original reaction, published in 1883, 117 consisted of the condensation of a phenol derivative with a β-ketoester catalyzed by Brønsted acids (such as sulfuric acid). Despite several advantageous modifications, which included the use of milder acids, this process still requires a large quantity of acid, as well as having a limited substrate scope.…”