P-Hydroxyphenylarsonic acid

In a 2-1. round-bottom flask is placed 218 g. (1 mole) of p-hydroxyphenylarsonic acid (Note 1) and 375 cc. of water. A solution of 180 g. (4.5 moles) (Note 2) of sodium hydroxide in 375 cc. of water is added, and the mixture shaken until a homogeneous solution is obtained. After cooling to 40-50° there is added 189 g. (2 moles) of chloroacetic acid in small portions (Note 3) with stirring, and the clear solution is refluxed for four hours. At the end of this time the mixture is cooled to 20°, filtered to remove a slight flocculent precipiLaLe, and the -arsonophenoxyacetic acid precipitated (Note 4) by the addition of 200 cc. (2.1 moles) of hydrochloric acid (sp. g. 1.19). The product is filtered on a 10-cm. Buchner funnel and washed with three successive 100-cc. portions of cold water. It is then crystallized from 2 1. of hot water (Note 5), filtered, and washed... 

One hundred and forty-four grams (0.60 mole) of the dry mono-sodium salt of p-hydroxyphenylarsonic acid [Org. Syntheses Coll. Vol. 1, 490 (1941)] is added portionwise with stirring and cooling to 450 ml. of concentrated sulfuric acid. A mixture of 39 ml. of nitric acid (sp. gr. 1.4) and 39 ml. of concentrated sulfuric acid is added with continuous stirring and sufBcient cooling to hold.the temperature of the reaction mixture below 0°. The temperature is then allowed to rise to 10° over a period of several hours. The reaction mixture is poured into 2250 ml. of water and allowed to stand for 24-48 hours. The precipitated 3-nitro-4-hydroxyphenylarsonic acid is filtered off and washed with saturated aqueous sodium chloride solution until free of sulfuric acid and then with water until free of salt. The dry product is obtained in a yield of 65-75%. 

Hydroxyl Groups. Although o- and p-aminophenols have been converted into 0- and p-hydroxyphenylarsonic acids in satisfactory yields (35-90%), - the reaction fails with the meta ismner. Several substituted hydroxyphenylarsonic acids have been prepared by the Bart reaction. Following are a number of examples ... 

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... 

Detailed procedures for the preparation of arsanilic acid and sodium p-hydroxyphenylarsonate, by arsonation of aniline and phenol, respectively, are published in Organic Syntheses.79> 80... 

Hydroxy-4-acetylphenylarsonic acid 3-Acetyl-4-hydroxyphenylarsonic acid p-Arsonophenylacetic acid... 

A mixture of a solution of 31.6 g. (0.136 mole) of 3-nitro-4-hydroxy-phenylarsonic acid (p. 224) in 600 ml. of methanol and 840 g. of 4% sodium amalgam [Org. Syntheses Coll. Vol. 1, 554 (1941)] is heated to reflux on a water bath until there is no more evolution of gas. The alcohol is removed by distillation, and the residue is treated with 120 ml. of water. The mercury is separated, and 150 ml. of concentrated hydrochloric acid is added to the aqueous phase. After standing for a day, the mixture is filtered and the filtrate treated with activated carbon. Sodium hydroxide solution (0.10 N) is added until the solution is just on the alkaline side of Congo red but is acid to litmus. Acetic acid (25 ml.) is added to complete the precipitation of the 3-amino-4-hydroxyphenylarsonic acid, which is removed by filtration after cooling. The precipitate is washed with water until free of chloride ion and dried. The yield is around S7 fo. 

It is prepared by treating sodium p-hydroxyphenylarsonate (37) with a mixture of nitric acid and sulphuric acid at O C [32],... 

Synonyms Arsonic acid, (4-hydroxy-3-nitrophenyl)- 4-Hydroxy-3-nitrobenzenearsonic acid 2-Nitro-1-hydroxybenzene-4-arsonic acid 3-Nitro-4-hydroxybenzenearsonic acid 3-Nitro-4-hydroxyphenylarsonic acid Nitrophenoloarsonic acid Empirical CeHeAsNOe Formula HOC6H3(N02)AsO(OH)2 Properties Pale yel. cryst. or It. tan powd. sol. in methanol, acetic acid, alkalis, DMSO sol. 10-50 mg/ml in 95% ethanol sparingly sol. in dil. min. acids sol. < 1 mg/ml in water, acetone insol. in ethyl acetate, ether m.w. 263.04 m.p. > 300 C Toxicology ACGIH TLV/TWA 0.2 mg(As)/m ... 

Organic arsenicals such as arsenilic acid, 3-nitro-4-hydroxyphenylarsonic acid, 4-nitrophenylarsonic acid, and p-ureidobenzenearsonic acid have been used as a feed additive since the 1950 s [4]. The U.S. Food and Administration approves of all four of these compounds for use in poultry and swine feeds but only at levels low enough to preclude residues in edible animal tissues which would be hazardous to human health [10]. In France and other countries almost all uses of these compounds are forbidden. 

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