Sustainable and scalable synthesis of polysubstituted bis-1,2,4-triazoles, bis-2-iminothiazolines and bis-thiobarbiturates using bis-N,N-disubstituted thioureas as versatile substrate

Abstract

An expedient and tandem regioselective one-pot protocol for the sono-synthesis of bis-[1,2,4]-triazol-3-yl amines and bis-2-iminothiazolines from corresponding bis-1,3-disubstituted thioureas has been developed. The products' regioselectivity correlate well with the pKas of the parent amines, in which the amine possessing higher pKa goes to the ring nitrogen, whereas the other nitrogen remains flanked as an exocyclic nitrogen of the bis-triazole or bis-thiazole moieties. Further, the sonochemical preparation of both bis-5-(2-nitrobenzylidene) thiobarbiturates and bis-2-thioxoimidazolidine-4,5-diones from bis-1,3-disubstituted thioureas has also been achieved. The obtained bis-5-(2-nitrobenzylidene)thiobarbiturates easily underwent reductive cyclization to afford the corresponding bis-5-benzo[c]isoxazol-3-ylidenethiobarbiturates. The scope and limitations of these strategies have been studied. Moreover, the suggested methodologies have advantages such as broad functional group tolerance, mild conditions, operational simplicity and applicability on a gram scale. Furthermore, the protocols scored well in a number of green metrics, subsequently showing these approaches to be environmentally benign and sustainable processes.

Keywords

• regioselectivity
• ultrasonic irradiation
• bis-[1,2,4]-triazol-3-yl amines
• bis-2-iminothiazolines
• green metrics