Organic sulfur compounds. V. The preparation of some benzothiazine hydroxamic acids

Abstract

-ox~-l,4-benzothiazine hydroxamic acids (VI) were best prepared by the reduction of a-(0-nitropheny1thio)cinnamates and related compounds of general structure V with sodium borohydride and palladium-charcoal. These precursors (V) were obtained by reacting methyl (0-nitropheny1thio)acetate and its simple derivatives with a variety of aryl aldehydes, in the presence of piperidine. Attempts to prepare the sulfones of V in a similar manner from methyl or ethyl (0-nitrobenzenesu1fonyl)acetate were successful in two instances when absolute methanol or ethanol was the solvent. The alternative reaction, in which one molecule of the aldehyde condensed with two molecules of the (o-nitrobenzenesulfonyl)acetate, also occurred.Methyl and ethyl (2-nitrobenzenesulfonyl)acetate and their simple ring-substituted derivatives were smoothly hydrolyzed and decarboxylated by heating a solution of the acetate in aqueous alcohol containing piperidine. Methyl p-nitrophenylsulfone is similarly obtained in an excellent yield from methyl (p-nitrobenzenesu1fonyl)acetate. Neither methyl (o-nitropheny1thio)acetate nor methyl ol-(4-trifluoromethyl-2-nitrobenzenesulfonyl)propionate is affected by this treatment.Canadian Journal of Chemistry. Volume 45. 975 (1967) The-preparation of a variety of 2H-1,4-tion was an investigation of the reactivity benzothiazine hydroxamic acids possessing of the methylene group in IIa, in view of general structure Ia was the subject of two the fact that the corresponding lactam IIb recent publications (1, 2). Because com-is known (5) to react with aryl aldehydes pounds structurally related to I are known and other compounds. Attempts to conto possess antibacterial activity (3), and dense IIa and benzaldehyde in the presence because some derivatives of I have been of piperidine were unsuccessful, though the shown recently (4, and unpublished results) methylene group of IIa was sufficiently to be reactivators of organophosphorus-active to react with amyl nitrite and gave inhibited cholinesterase, it was necessary to the oximino-hydroxamic acid 111. The synthesize other derivatives of 3,4-dihydro-alternative method (Reaction Scheme 1) 4-hydroxy-3-oxo-2H-1,4-benzothiazine was used for the preparation of the required compounds (VI). The intermediates V fixxi# \ os& \ were I), although obtained when in fair o-chlorobenzaldehyde to good yields (Table or T o R'T o I vanillin was used no products were isolated. of a-(2-nitrophenoxy)cinnan~ates (V, 0 (IIa) for future antibacterial testing and replacing S ) from methyl (2-nitro~henox~)-pharmacolog-ical evaluation. The desired acetate and aryl aldehydes failed, as a products were 2-arylidene-3,4-dihydro-4-result of the reduced reactivity of the hydroxy-3-oxo-2H-1,4-benzothiazines (VI) , methylene group of the (2-nitrophenoxy)-and the initial approach to their prepara-acetate compared with that of the (2-nitropheny1thio)acetates (cf. ref. 6).

Notizen zur Synthese von 2‐Aminophenylsulfonen

“…Als Methode zur Herstellung von Methyl-(2-nitrophenyl)-sulfon (1) -einem potentiellen Zwischenprodukt fur die Synthese von 2-Aminophenyl-methyl-sulfon (2) -ist in der Literatur neben der Oxydation von 2-Nitrophenyl-methyl-sulfid (2-Nitro-thioanisol) 111 [2] und neben der Umsetzung des Silbersalzes von 2-Nitrobenzol-sulfinsaure (3) mit Methyljodid [3] insbesondere die Decarboxylierung von 2-Nitrophenylsulfonylessigsaure (4) beschrieben [4] [5] (vgl. auch [6] [lo] fuhrte dann problemlos zum angestrebten 2 (vgl. auch [ 111 [12]).…”

“…Als hellgelbe o l e werden so in roher Form erhalten: 214,l g (SS,l%) Butyl-(2-nitrophenyl)-sulfon (9c), 233,4 g (90,8%)2-Nitrophenyl-pentyl-suljon (9d), 259,6 g (95.8%) Hexyl-(2-nitrophenyl)-sulfon (9e), 228,5 g (88,9%) Neopentyl-(2-nitrophenyl)-suljon (9j). ; 7,40-7,22 (m, 1 H) ;6,68 (m,2 H);5,16 (2 H);3,91 (m,IH);2,13 (m,10 H)]; 180,7 g (77,6%) 2-Aminophenyl-phenyl-sulfon (10k) analysenreine Probe (Smp. 119-120") durch Umkristallisation von 1 g aus 5 ml 95proz.…”

“…auch [6]). Durch eigene Versuche konnten die in [ 11 erwiihnten negativen Resultate bestatigt werden, wonach 1 nicht durch Umsetzung von Dimethylsulfat oder Methyljodid mit dem Natriumsalz von 3 synthetisierbar ist.…”