No abstract

No abstract

Preparation of 3-Hydroxypyrazolines (Table I). Hydrolysis Procedure.-A mixture of 10.0 g (0.059 mol) of 3-acetoxy-3,5,5trimethylpyrazoline-Is and 30 ml of 5% methanolic sodium hydroxide was stirred at room temperature for 10 hr. It was diluted with water and carefully neutralized with 5% HC1. After extraction with ether, drying (MgS04), and concentration, distillation yielded 6.1 g (81%) of 3-hydroxy-3,5,5-trimethyl-1-pyrazoline: ir (neat) 3378 (OH), 1560 cm-1 (N=N); nmr (neat) 1.32, 1.42, 1.58 (s, 3, CCH3), 1.53 (m, 2, CH2), 5.88 (s, 1, OH).Hydrogenolysis Procedure.-A solution of 17.0 g (0.1 mol) of 3-acetoxy-3,5,5-trimethyl-1-pyrazoline in 100 ml of CH3OH was added, dropwise and with stirring, to a solution of 37.85 g (1 mol) of sodium borohydride in 450 ml of CH3OH. This mixture was heated under reflux for 1 hr, cooled, diluted with water, concentrated to half its volume, and extracted with five 50-ml portions of CHCls. The CHC13 extract was dried (MgSO<), concentrated, and distilled to yield 11.0 g (86%) of 3-hydroxy-3,5,5-trimethyl-1-pyrazoline.3-(3,5-Dinitrobenzoyloxy)-3,5,5-trimethyl-l-pyrazoline.-To a cold mixture of 1.65 g (0.0078 mol) of 3,5-dmitrobenzoic acid and 2.8 g (0.016 mol) of benzenesulfonyl chloride in 15 ml of pyridine was added 1.0 g (0.0078 mol) of 3-hydroxy-3,5,5-trimethylpyrazoline (6a). The mixture was stirred for 4 hr, poured into water, and filtered, and the residue was recrystallized from C2H:,OH-C6H6 to give 0.7 g (28%) of the title compound, mp 162-163°.3-Methoxy-3,5,5-trimethyl-1-pyrazoline. Procedure A.-An ether suspension of the sodium salt of 6a was prepared by adding 12.3 g (0.096 mol) of 6a to a suspension of 2.2 g of sodium in ether. This mixture was stirred at room temperature for several days to ensure complete reaction. Methyl iodide (28.4 g, 0.2 mol) was added dropwise and the mixture was heated under reflux for 24 hr. It was filtered, dried, and distilled to give 9.9 g (73%) of 3-methoxy-3,5,5-trimethylpyrazoline-l: bp 22°( 0.25 mm); ir (neat) 1655 (N=N), 1201 cm-1 (COC); nmr (CDC13) 3.75 (s,

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.

No abstract