Nitrophenylacetic acid

In a i-l. round-bottom flask are placed 100 g. of -nitrobenzyl cyanide. A solution of 300 cc. of concentrated sulfuric acid (sp. gr. 1.84) in 280 cc. of water is prepared, and two-thirds of this solution is poured on to the -nitrobenzyl cyanide. The mixture is shaken well, until the solid is all moistened with the acid. Any solid material sticking to the walls of the vessel is now washed down into the liquid with the remainder of the acid, the flask is attached to a reflux condenser, then set, without shaking, over a 10-cm. hole in a large sheet of asbestos board which rests on a tripod, and heated until the mixture boils. The boiling is continued for fifteen minutes. 

The reaction mixture, which becomes rather dark, is diluted with an equal volume of cold water and cooled to o° or below. The solution is filtered, the precipitate is washed several times with ice water and then dissolved in 1600 cc. of boiling water. (A few grams of animal charcoal are added in dissolving the precipitate, if a technical -nitrobenzyl cyanide has been used.) This solution is filtered as rapidly as possible through a large folded filter, preferably with a steam funnel. In spite of all precautions, however, some solid usually separates on the filter. This must be rcdissolved in a minimum quantity of boiling water, and this solution then filtered into the main solution. The 

If the flask is not protected with an asbestos board or the equivalent, decomposition occurs where the substance is superheated on the side walls of the flask. If crystals of the cyanide are allowed to remain on the upper walls of the flask, they are not easily washed down and so are not hydrolyzed. 

The solubility curve of / -nitrophenylacetic acid is very steep at temperatures near ioo°, so that the filtering of the boiling solution should be rapid. 

If a good grade of cyanide be used, it is not necessary to add bone-black in order to obtain the acid in a pure state. 

CgHsCHjCN + HNOa — p-NOjCeH CHjCN (main product) + HjO 

CeHsCKjCN -f HNO3 — p-NOjC.H CHjCN (main product) -f H O 

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Thionyl chloride (11.5g, 96.4 mmol) was added to 2-nitrophenylacetic acid (8.72g, 48.2mmol) and the suspension was warmed to 50°C and stirred until gas evolution was complete. The resulting solution was concentrated in vacuo and the residue dissolved in CHjClj (30 ml). This solution was added dropwise to a stirred solution of Meldrum s acid (6.94 g, 48.2 mmol) in CH2CI2 (200 ml) under nitrogen at 0 C. The solution was stirred at 0" C for 1 h after the addition was complete and then kept at room temperature for an additional hour. The reaction solution was then worked up by successively washing with dil. HC1, water and brine and dried (MgSOJ. The dried solution was concentrated in vacuo and abs. ethanol (200 ml) was added to the residue. The mixture was... 

Bromo-2-nitrophenylacetic acid (26 g, 0.10 mol) was dissolved in a mixture of 50% HjSO (400 ml) and ethanol (600 ml) and heated to 90°C. Over a period of 1 h, zinc dust (26.2 g, 0.40 mol) was added. slowly and then heating was continued for 2 h. The excess ethanol was removed by distillation. The solution was cooled and filtered. The filtrate was extracted with EtOAc. The filtered product and extract were combined, washed with 5% NaCOj and brine and then dried (MgSO ). The solvent was removed in vacuo and the residue recrystallized from methanol to give 20.5 g (97% yield) of the oxindole. 

Nitrophenylacetic acid [3740-52-1] M 181.2, m 120 , pK 3.95. Crystd from EtOH/water and dried over P2O5 under vacuum. 

Methyl 5-methoxyindole-2-acetate lndole-2-acetic acid, 5-methoxy-, methyl ester (8) 1H-lndole-2-acetic acid, 5-methoxy-, methyl ester (9) (27798-66-9) 5-Methoxy-2-nitrophenylacetic acid Acetic acid, (5-methoxy-2-nitrophenyl)- (8) Benzeneacetic acid, 5-methoxy-2-nitro- (9) (20876-29-3)... 

Sodium methoxide, 3-methyl-4-nitroanisole, diethyl oxalate, 30% hydrogen peroxide, 97% sodium hydride, methyl acetoacetate, sodium sulfate, 10% palladium on activated carbon, ammonium formate, and 2-nitrophenylacetic acid were purchased from Aldrich Chemical Company, Inc., and were used without further purification. 

Tandem Passerini/Knoevenagel reactions were also performed by employing 2-nitrophenylacetic acid as the acid component to give the butenolides 65 that were reduced to the intermediate amines 66, which immediately cyclized to give indoles 67 in very high yields via a ring-switching process (Scheme 2.24) [52],... 

The synthesis of compound (88) is outlined in Scheme 3.13. DCC coupling of enantiomerically pure (1. S, 2.V)-(+)-tra i-2-pyrrolidinyl-(V-methylcy-clohexylamine (92) with 2-nitrophenylacetic acid gave the nitro derivative (93). Catalytic hydrogenation over Pd-C catalyst afforded amine (94) which was treated with thiophosgene to yield (88). 

Nitrophenylacetic acid [3740-52-1 ] M 181.2, m 141-142.5°, pK 3.95. The acid crystallises as yellow needles from EtOH, EtOH/water and dry it over P2O5 under vacuum. The amide has m 160-161° (from C6H6 plates or EtOH, needles). [Beilstein 9 III 2282,9 IV 1687.]... 

The method of Leupold was used to prepare 3-( -nitrobenzyli-dene)phthalide in a 42% yield by the condensation of phthalic anhydride with 2 -nitrophenylacetic acid in the presence of potassium acetate m.p. 227-229 C (lit m.p. 222 C). The nitro compound was reduced by the conventional stannous chloride reduction to give 3-(p -aminobenzylidene)phthalide in a 64% yield. Recrystallization from aqueous acetone gave pale yellow needles m.p. 233 C. 

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