A facile and efficient one-pot 3-component reaction (3-CR) method for the synthesis of thiazine-based heterocyclic compounds using zwitterion adduct intermediates

Abstract

Multicomponent reactions (MCRs) are considered a green strategy by generating diversity of scaffolds from less synthetic effort and safe conditions. This work present the synthesis of dimethyl 8-(tert-butylamino)-4-oxo-4,6-dihydropyrimido[2,1-b][1,3]thiazine-6,7-dicarboxylate in low to moderate yields 33–74 % from the prepared 2-amino-4H-1,3-thiazin-4-one derivatives containing both an acidic proton and a suitable nucleophile with alkyl isocyanides and DMAD/DEtAD. The work portrays facile method under green chemical production processes using green solvents such as acetone, ethanol, isopropanol, and 2-methyl-tetrahydrofuran. This chapter shows the flexibility of zwitterion adduct from the reaction of alkyl isocyanide and DMAD. The zwitterion adduct is trapped by 2-amino-4H-1,3-thiazin-4-one derivatives and forms fused [6-6] heterocyclic compounds. The preparation of starting material thiazine was carried out at different condition from 0 °C temperatures to reflux, while the synthesis of novel dimethyl 8-(tert-butylamino)-4-oxo-4,6-dihydropyrimido[2,1-b][1,3]thiazine-6,7-dicarboxylates was done at room temperature without the use of catalyst.