An Efficient and Facile Multicomponent Reaction for the Synthesis of 5′,6′‐dihydro‐6′‐hydroxy‐6′‐(trifluoromethyl)‐1′H‐spiro[indoline‐3,4′‐pyrimidine]‐2,2′(3′H)‐dione Derivatives under Solvent‐Free Conditions

Abstract

The reactions of isatins, urea, and different diketones under solvent‐free conditions have been developed for the preparation of novel spiroheterocycles. It was found that these reactions could be given higher yields and required shorter time compared with commonly used volatile organic solvent conditions. In this synthesis, the important group trifluoromethyl was introduced into the structure of the products. The pure products could be obtained only through removing TsOH, isatins, and urea from hot water. At same time, diketone was eliminated through a small amount of EtOH. Other advantages of this method are simple setup, mild conditions, and minimal environment impact.

Trifluoromethyl‐β‐dicarbonyls as Versatile Synthons in Synthesis of Heterocycles

“…[240] Xu et al disclosed an environmentally benign, efficient synthesis of 5',6'-dihydro-6'-hydroxy-6'-(trifluoromethyl)-1'Hspiro[indoline-3,4'-pyrimidine]-2,2'(3'H)diones 416 via threecomponent Biginelli reaction of isatins 415, trifluoromethyl-βdiketones 1 and urea 313 using p-TsOH as catalyst under solvent-free conditions (Scheme 143). [241] This solvent-free approach has advantages over the solvent mediated synthesis in terms of low cost, short reaction time, mild reaction conditions and high yields.…”