A Mechanistic Approach to Liquid-Assisted Mechanochemical Synthesis of 5-Aryl/Spiro-[1,2,4]-triazolidine-3-thiones

1,3-dimethylbarbituric acid-H2O mediated liquid assisted mechanochemical route has been developed for the synthesis of a wide array of 5-aryl/spiro-1,2,4-triazolidine-3-thiones, via in situ generation of benzylidene/alkylidene barbiturates, followed by tandem, base-driven Michael addition reaction and rearrangement of the pyrimido[4,5-e][1,2,4]triazepine intermediate. The method is an application of mechanochemistry in organic synthesis. It is efficient, easy to follow and avoids the tedious steps of catalyst preparation and chromatographic separation. Moreover, the protocol is compared to on-water, room temperature approach and the reaction mechanism has been revisited with the aid of experiments.

Automated summary

In this study, a liquid-assisted mechanochemical route mediated by 1,3-dimethylbarbituric acid-H2O was developed for the synthesis of a wide array of 5-aryl/spiro-1,2,4-triazolidine-3-thiones. The method is efficient, easy to follow, and avoids the tedious steps of catalyst preparation and chromatographic separation. The protocol was compared to an on-water, room temperature approach and the reaction mechanism was revisited through experiments.