1,2,4-Oxadiazines and 1,2,4-Thiadiazines

The 6-membered aza-heterocycles, 1,2,4-oxadiazines and 1,2,4-thiadiazines, are valuable scaffolds due to the vast spectrum of medicinal properties they possess. These scaffolds exist in several drugs or drug-leads such as MK-8428, mS-11, BPDZ44, and IDRA21. These can be classified as 2H-, 4H- or 6H-isomers depending upon the position of double bonds in the ring. The sulfur in thiadiazines exists in different oxidation states, namely, SII, SIV and SVI, of which SVI (1,2,4-benzothiadiazine-1,1-dioxide) is the most common oxidation state. This article discusses various methods such as cycloaddition, rearrangement and CH functionalization for the synthesis of 1,2,4-oxadiazines and 1,2,4-thiadiazines and their biological properties.