Preparation of potentially bioactive aza and thiaza polycyclic compounds containing a bridgehead nitrogen atom. Synthesis of pyrrolo[1,2,3‐de]‐1,4‐benzothiazine derivatives

Abstract

The synthesis of some pyrrolo[1,2,3‐de]‐1,4‐benzothiazine derivatives by using a modified Bischler type cyclization of N‐(2,2‐diethoxyethyl)‐2H‐1,4‐benzothiazines as a crucial step is described. The alternative approach based on Friedel‐Crafts alkylation of the N‐(2‐chloroethyl)‐2H‐1,4‐benzothiazines is shown to be impractical due to the low yield obtained.

2-(3-Oxo-3,4-dihydro-2H-1,4-benzothiazin-4-yl)acetohydrazide

“…For the biological and medicinal activity of 1,4-benzothiazine compounds, see: Armenise et al (1991); Gupta et al (1993); Vicente et al (2009); Schiaffella et al (2006); Kaneko et al (2002). For the pharmacological properties of hydrazones and their derivatives, see: Sivasankar et al (1995); Satyanarayana et al (2008).…”

2-(3-Oxo-3,4-dihydro-2H-1,4-benzothiazin-4-yl)acetic acid monohydrate

“…For the biological activity of 4H-benzo(1,4)thiazine, see: Armenise et al (1991); Gupta et al (1993); Fringuelli et al (2005). For medical applications of sulfone derivatives of 4Hbenzo(1,4)thiazine, see: Shinji & Koshiro (1995); Szule et al (1988); Culbertson (1991).…”

“…A number of molecules containing the 4H-benzo(1,4)thiazine nucleus in their structures exhibit a broad spectrum of biological activity, including antibacterial (Armenise et al, 1991), anticancer (Gupta et al, 1993), anti-rheumatic, antiallergic, vasorelaxant, anti-arrhythmic and anti-hypertensive (Fringuelli et al, 2005) properties. The sulfone derivatives of 4H-benzo(1,4)thiazine have been reported to find a number of applications in medicine (Shinji & Koshiro, 1995;Szule et al, 1988;Culbertson, 1991).…”

Diethyl 1-benzyl-2,2-dioxo-4-phenyl-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[2,1-c][1,4]thiazine-1,3-dicarboxylate

“…For the biological and pharmacological properties of compounds containing the pyrrolidine sub-structure, see: Hemming & Patel (2004); Kueh et al (2003). For biological properties of compounds containing the pyrrolothiazine scaffold, see: Armenise et al (1991Armenise et al ( , 1998. For ring puckering analysis, see: Cremer & Pople (1975).…”

“…Compounds containing the pyrrolothiazine scaffold have also been shown to exhibit anti-inflammatory, anti-fungal and anti-microbial activities (Armenise et al, 1998;Armenise et al, 1991).…”