The synthesis of novel spirocyclic N-aryl-substituted 2-thiopyrimidine-4,6-diones

Abstract

A convenient and efficient method for the synthesis of new unsaturated spiro-annulated N-aryl-4,6-dioxopyrimidine-2-thione derivatives has been developed. The resulting compounds can be potential biological active molecules or precursors for further chemical modification. Aim. To develop the methods for the synthesis of new unsaturated spiro-annulated 2-thiopyrimidine-4,6-dione derivatives, which can be used as potentially biological active molecules or precursors for their formation. Results and discussion. By condensation of N-aryl-substituted thioureas and allylmalonic acid using acetic anhydride or acetyl chloride the series of 5-allyl-substituted 2-thiopyrimidinediones has been synthesized. Their further alkylation with allyl bromide or metallyl chloride led to formation of 5,5-dialkenyl derivatives, which were converted to the corresponding unsaturated spirocyclic dioxopyrimidine-2-thiones by ring-closing metathesis. Experimental part. The synthesis of the starting compounds and title products was performed by preparative chemical methods, TLC and column chromatography, elemental analysis, NMR-spectroscopy. Conclusions. The efficient three-step synthetic route of new unsaturated spiro-annulated N-aryl-4,6-dioxopyrimidine-2-thione derivatives from the starting N-arylsubstituted thioureas and allylmalonic acid has been developed. The spiro-annulated products obtained can find application in biological and pharmaceutical science or as starting substrates for further chemical modification.

Keywords

• nitrogen heterocycles
• spiro-annulation
• thiopyrimidinedione
• metathesis
• grubbs catalyst