Isatin, nitration

Nitration of isatin,217,218 7-methylisatin,8 4,7-dimethylisatin,21 and 1-ethylisatin147 leads to the introduction of the nitro group into the 5-position. Nitration of 5-methylisatin gave 5-methyl-7-nitroisatin.8,21... 

The synthesis of antiviral spiro-(3-lactam 51 begins with the benzylation of isatin 45 to give 1-benzylisatin 46, which affords Schiff s base 47 on reaction with anisidine in ethanol. The Schiff s base 47 on treatment with methoxyacetyl chloride by the chloride-imidate cycloaddition [85] route afforded a mixture of spiro E- and Z-azetidin-2-ones 48 and 49, which were separated by chromatography. The (Z)-N-arylazetidin-2-one 49 was further converted to desired 4-spiro-(3-lactam 51 by treatment with ceric ammonium nitrate and subsequently with tetrabutylammonium bromide in THF in the presence of pulverized KOH (Scheme 13). 

Nitration, 4-acetaminobiphenyl, 211 4-acetamino-l,3-dimethylbenzene, 211 2-acetaminonaphthalene, 212 benzonitrile, 215 cumene, 220 dibenzothiophene, 220 o-dichlorobenzene, 112 2,4-dimethylaniline, 131 ethyl acetoacetate, 159 ethylbenzene, 223 fluorobenzene, 223 p-hydroxyphenylarsonic acid, 224 isatin, 225 isoquinoline, 225 lepidine, 226... 

Reactions of Indoles. 2-Arylindoles react with tosyl azide under phase-transfer conditions to give 3-diazo-compounds (148). The phenylazoindole (149 R = N2Ph) is converted into the nitroindole (149 R = NO2) by ipso-nitration. Indoles are oxidized by thallium(III) nitrate to mixtures of oxindoles and isatins. Sensitized photo-oxygenation of the indole (150) yields the hydroperoxide (151), which forms compound (152) on treatment with methanolic potassium borohydride. Vilsmeier-Haack formylation of... 

Iron (III) nitrate, anhydrous 1737 IsatInIc acid anhydride 2068... 

Phenyl-3-propoxyclnconlc acid (3)4 To a solution of 33% KOH (25 ml.) were added isatin 1 (21.05 g, 0.15 mol) and a-propoxyacetophenone 2 (26.7 g, 0.15 mol). Enough EtOH was added to render the mixture homogeneous and this was heated to 100 C lor 48 h. After decoiorizatlon with charcoal the nitrate was acidified with 50% AcOH and the product 3, mp 216 0 (40%), was recrystaKzed from dlute EtOH or MejCO. 

Baeyer confirmed his results by the total synthesis of oxindole, isatin and indole. Nitration ofphenylacetic acid, isolation of the o-nitro isomer, and reduction of the latter followed by ring closure gave oxindole. Reaction with nitrous acid ( .e. potassium nitrate and sulfuric acid) gave isatin oxime, from which by reduction, dehydrogenation with iron(lll) chloride and final hydrolysis, isatin itself was obtained. 

Baeyer nitrated phenylacetic acid, and reduced this to o-aminophenylacetic acid, which lost water to form oxindole. By reducing nitroso-oxindole (prepared by Baeyer and Knop) to amino-oxindole, and oxidising this, Baeyer obtained isatin ... 

Polychromatic reagents Moffat and Lyttle (42) developed a polychromatic ninhydrin reagent. It consisted of (a) ninhydrin (0.2%) in ethanol (50 ml) + acetic acid (10 ml) + 2,4,6-collidine (2 ml) and (b) a solution of copper nitrate (1.0%) in absolute ethanol. The two solutions are mixed in a ratio of 50 3 before use. Krauss and Reinbothe replaced ethanol by methanol (43) and also achieved polychromatic amino acid detection by joint application of ninhydrin and primary, secondary, or tertiary amines. The layers were first sprayed with diethylamine, dried for 3 min at 110°C, cooled, and then sprayed with 0.2% methanolic ninhydrin and heated for 10 min at 110°C, when the spots of amino acids appeared on a pale blue background. Use of ninhydrin (0.27 g), isatin (0.13 g), and triethylamine (2 ml) in methanol (100 ml) gave spots of amino acids on a yellow background. 

Ramin et al. performed the combination of isatin, barbituric acid, and cyclohexane-l,3-dione derivatives in the presence of alum (KAl(S04)2 l2H20) as a catalyst in [BMIM][PF6] to afford spiro[chromeno[2,3-d]pyrimidine-5,3 -indoline]-tetraones 183 after 15 min at 100 °C (Scheme 107). A total of eight types of substituted isatins, two types of 1,3-cyclohexanediones, and three types of barbituric acids were used in this tactic for the library validation. The authors investigated tiie catalytic effect of other Lewis and Bronsted acids such as SSA (silica sulfuric acid), SnCb, p-TSA (para-toluenesulfonic acid), and CAN (ceric ammonium nitrate) under this methodology and foxmd that alum at 10mol% demonstrated significant capability and promotion of reaction rate in [BMIM][PF6] as reaction medium [287]. 

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