Organic Sulfur Compounds: Part I. Benzothiazine Hydroxamic Acids and Related Compounds

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I\BSTR~\CT T h e products obtained wher a-(0-~~itrophen~lthio) acids are reduced b y means o f sodi~~lll borohydride and palladi~lm-charcoal depend on ( a ) the reaction temperature, ( b ) the solvent, ( G ) the length o f time in which the a-(0-nitrophenylthio) acid is in contact with the reducing agent, and (d) the nature o f the substituents on the a-(0-nitrophenylthio) acid. B y varying theseconditions, benzothiazine hydroxamic acids (i.e. s~~bstituted 3,4-dihydro-4-hydroxy-3-0x0-Z-1,4-benzothiazines), the corresponding lactallls (3,4-dihydr0-3-ox0-2H-1,4-benzothiazines, and derivatives of 2-carboxymethyIthioazobenze~:e can be prepared. In t\vo cases, additional products were obtained. W h e n (o-r~itrophe~~ylthio)acetic acid was catalytically reduced for 30 min in dioxane, 3,4-dihydro-3-0x0-2H-1,4-benzothiazine-l,1-dioxide (VIG) was an ~~ilexpected product, and when a-(4-trifl~1oromethyl-2-nitrophe11ylthio)-isob~~tyric acid was left for a prolonged time in contact with sodi~lirl borohydride and palladi~im-charcoal, a derivative o f hydrazobenzene, namely, 2-carboxy(a,a-dimethyl)methylthio-5-trifl~~orornethylhydrazobe~ize~~e (V), was one o f the three identified products.When reduced by means of sodium borohydride and palladiu~n-charcoal, certain aromatic nitro compounds which possess an ester group in a position suitably orientated with respect to the o-nitrophenyl group are converted into cyclic hydroxamic acids (1-3) ; the nitro group is reduced to a hydroxylanlino group which then cyclizes with the ester function. When t\vo nitro acids were reduced by siiuilar means, hoxvever, complete reduction to the corresponding amines occurred, and in both cases, lactamisation resulted on acidification (1).We have recently reported (3) that 2H-1,4-benzothiazine liydroxamic acids (I) are readily obtained by reducing suitably substituted (0-nitropl~enylt1~io)acetates bjr means of sodium borohydride and palladium-cliarcoal. On the suppositioil that reductioil of the corresponding acids would yield the related lactains (111), n-hich could be expected to possess anthelinintic properties (4, 5), substituted (0-nitropheny1thio)acetic acids were reduced sodiuin borohydride and palladium-charcoal. The resulting products depended on (a) time, (b) solvent, (c) nature of the substituents, and (d) temperature.When a-(4-trifluoroi~~etl~yl-2-nitrophenylthio)propionic acid (IIJ) was reduced in dioxane or illethanol over a period of 30 min n-ith excess sodium borohydride in the presence of palladium-charcoal, the corresponding anlino compound n-as not formed (6). The isolatioil of 6-trifluorometl~yl-3,4-dihydro-4-11ydroxy-2-~11et11yl-3-oxo-2H-l,4-benzothiazine (If) in good yield, on acidification of the filtrate, indicated that reductioil had proceeded only as far as the hydroxylamino stage. This reaction is a general one. For personal use only.

Section: Methodsmentioning

confidence: 99%

ORGANIC SULFUR COMPOUNDS: II. CATALYZED SODIUM BOROHYDRIDE REDUCTIONS OF SELECTED α-(o-NITROPHENYLTHIO) ACIDS

Coutts¹,

Barton²,

Smith³

1966

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“…The mother liquor remaining after the removal of 4a was cooled and from it the spiro[benzothiazoline-2,4'- [2]pyrazolone] (3a, 0.46 g) slowly deposited as dark yellow needles, mp 153-154 "C. Its ir spectrum was identical to that of product B described in preparation i. (ii) Ammonium chloride (0.2 g) in water (10 ml) was added to a solution of title compound (1.0 g) in 60% aqueous ethanol (70 ml).…”

Section: Reducrion Of 3-melhyl-4-(2-nirrophen~~1rhio)-i-phenyl-2-mentioning

confidence: 99%

“…These data suggested that compound B was 3'-methyl-1'-phenylspiro[benzothiazoline-2,4'- [2]pyrazoline]-5'-one, 3a. Mass spectral evidence supported this structure.…”

mentioning

confidence: 96%

Derivatives of 2-pyrazolin-5-one. IV. Preparation and properties of two spiro[benzothiazoline-2,4′-[2]pyrazoline] derivatives

Coutts¹,

El-Hawari²,

Pound³

et al. 1976

Can. J. Chem. 54, 993 (1976). Reduction of 3-methyl-4-(2-nitrophenylthio)-1-phenyl-2-pyrazolin-5-one (20) with sodium borohydride and palladium-charcoal gave two products which are identified as 3'-methyl-1'-phenylspiro[benzothiazoline-2,4'-[2]pyrazoline]-5'-one (3a) and 4-(2-mercaptopheny1amino)-3-methyl-I-phenyl-2-pyrazolin-5-one (4a). Evidence is presented in support of a reaction mechanism in which the spiro compound 3a is formed first and is then further reduced to the thiol 4a.Reduction of the 1,3-diphenyl-4-(2-nitrophenylthio)-2-pyrazolin-5-one (26) with the same reducing agent proceeded in a similar manner and diphenyl products 36 and 46, analogous to the spiro compound 3a and the thiol4a, respectively, were formed.Some chemical properties of the thiol 4a were investigated; it formed a dimethyl derivative, a diacetate, and a tribenzoate.Reduction of the pyrazolones 20 and 2b with zinc and ammonium chloride produced the same spirobenzothiazolines 30 and 36. RONALD T. COUTTS, ABDEL-MONAEM EL-HAWARI, NORMAN J. POUND et RUDOLPH A.ABRAMOVITCH. Can. J. Chem. 54, 993 (1976).La reduction de la methyl-3 (nitro-2 phenylthi0)-4 phenyl-l pyrazoline-2 one-5 (20) par le borohydrure de sodium et le palladium sur charbon conduit a deux produits que I'on a identifie comme etant la methyl-3' phenyl-I' spiro[benzothiazoline-2,A'-pyrazoline-2lone-5' (3a) et la (mercapto-2 phtny1amino)-4 methyl-3 phenyl-l pyrazoline-2 one-5 (4a). On presente des donnees qui supportent un mecanisme reactionnel dans lequel un compose de type spiro 3a est forme dans une premiere etape pour @tre ensuite reduit en thiol 40.La reduction de la diphenyl-1,3 (nitro-2 pheny1thio)-4 pyrazoline-2 one-5 (26) par le m&me agent reducteur conduit de la m&me maniere a d e w produits diphenyles 36 et 46 analogues respectivement au compose spiro 3a et au thiol4a.On a examine quelques proprietes chimiques du thiol 4a; il forme un derive dimtthylt, un diacetate et un tribenzoate.Le reduction des pyrazolones 20 et 2b par le zinc et le chlorure d'ammonium conduit aux m@mes spirobenzothiazolines 3a et 36.[Traduit par le journal]Palladium-charcoal catalyzed sodium borohydride reductions of cr-(0-nitrophenylthio) aliphatic acids (1) and esters (2,3) produce cyclic hydroxamic acids whichare formed via hydroxylamine intermediates. A similar reduction (4) of the pyrazolone l a yielded the corresponding hydroxylamine 16 as the major product, together with a small amount of the amine lc. It was of interest to us to extend these reduction studies to see whether catalyzed sodium borohydride reductions of the related pyrazolones 2a and 2b would produce cyclic N-hydroxylated 'For part 111, see ref. 17. products. Hydroxylamines, however, were not isolated; instead, the reaction followed an unexpected pathway.Pyrazolones 2a For personal use only.

“…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.…”

mentioning

confidence: 99%

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

Coutts¹,

Smith²

1967

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-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).