Polycondensed heterocycles. IV. Synthesis of 1,4-Dioxo-2,3,3a,4-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzothiazine

A method for the synthesis of the title compound 3 consisted of an intramolecular cyclization in a stannic chloride catalyzed Friedel‐Crafts reaction of N‐(2‐methylthiophenyl)‐5‐oxoproline chloride 10, prepared by chlorination of the corresponding acid 9 obtained by hydrolysis of its ethyl ester 8. Condensation of 2‐methylthioaniline 4 with diethyl bromomalonate 5 afforded diethyl 2‐methylthioanilinomalonate 6 which gave 8 either directly by reaction with ethyl acrylate or by alkylation with ethyl β‐bromopropionate or ethyl acrylate and cyclization of resulting triethyl 2‐(2‐methylthio)anilino‐2‐carboxyglutarate 7. This method was not convenient because of the poor yield of 3 (14%). On the other hand, cyclization of N‐(2‐mercaptophenyl)‐5‐oxoproline 14 with DCC and DMAP provided 3 in 45% yield. Oxidation with m‐CPBA of the esters 11 and 8, demethylation via the Pummerer rearrangement of the respective sulphoxides 12 and 17 with TFAA and oxidation with iodine of resulting N‐(2‐mercap‐tophenyl)‐5‐oxoproline esters 13 and 18 gave the corresponding disulphides 16 and 19. Hydrolysis of these latter compounds and reduction of the resulting bis[2‐[2‐(hydroxycarbonyl)‐5‐oxo‐1‐pyrrolidinyl]phenyl] disulphide 15 with sodium dithionite afforded the required 14. Deprotection of t‐butyl ester 13 with TFA at 55° to obtain 14 led to 3 in 42% yield. Finally the Pummerer rearrangement of N‐(2‐methylsulphinylphenyl)‐5‐oxo‐proline 20 yielded the mixture of 14 and 15. Copyright © 1990 Journal of Heterocyclic Chemistry.