Microreactor Technology: Continuous Synthesis of 1H-Isochromeno[3,4-d]imidazol-5-ones

Abstract

A synthetic method was evaluated to form 1H-isochromeno[3,4d]imidazol-5-ones Wia ring closure starting from 3-amino-4-(arylamino)-1H-isochromen-1-ones. The method was implemented and optimized in a microreactor environment. It was possible to synthesize these compounds in a continuous mode with an output up to 2.2 g/h.

Continuous‐flow syntheses of heterocycles

“…For the pyrazole synthesis, the optimized batch microwave conditions-180 C, 1 s reaction time-could be directly translated to a flow process, whereby 225.8 g of 3,5-dimethyl-1-phenylpyrazole was formed in 1 h. In a similar manner, $51 g of 2-methylbenzimidazole were synthesized by reacting o-phenylenediamine with acetic acid under neat conditions at 270 C. The continuous synthesis of 1H-isochromeno[3,4-d]imidazol-5-ones starting from 3-amino-4-(arylamino)-1H-isochromen-1-ones was recently disclosed by Stevens and coworkers [43]. The ring closure was achieved by reacting the corresponding isochromenones and orthoesters in the presence of catalytic amounts of pTsOH at room temperature.…”