1,2-Thiazines and their Benzo Derivatives

Abstract

1,2-Thiazines are six-membered heterocyclic rings composed of four contiguous carbon atoms along with adjacent sulfur and nitrogen atoms. The nomenclature of 1,2-thiazines is complicated by various degrees of saturation of the ring atoms, double-bond regioisomers, and the multiple oxidation states of sulfur. A majority of the compounds encountered in this class of heterocycles exist as dioxides at sulfur. Particularly prevalent monocyclic compounds include the dihydro-1,2-thiazine 1,1-dioxides, tetrahydro-1,2-thiazine 1,1-dioxides, and 3,6-dihydro-1,2-thiazine 1-oxides. Recently, chemistry has been developed to synthesize the tetrahydro-1,2-thiazine 1,1-dioxide subclass via a transition metal-mediated C–H insertion reaction. A catalytic, asymmetric hetero-Diels–Alder cycloaddition reaction of N -sulfinylimine dienophiles with dienes has recently been developed for formation of enantiomerically enriched 3,6-dihydro-1,2-thiazine 1-oxides. Fully conjugated 1,2-thiazines have been prepared with both S( ii ) and S( vi ) oxidation states. The fused benzo derivatives of 1,2-thiazines are of great commercial importance due to their potent biological activity. Extensive studies have been performed on the synthesis and reactivity of these benzo derivatives. The most biologically active members of the benzothiazines, the oxicams, have a 1,2-benzothiazine 1,1,4-trioxide structure. The focus of this chapter is to update the literature from 1996 to 2006 on the physical and structural-properties, preparation, and applications of the 1,2-thiazines and their benzo derivatives.