O Hydrazinobenzoic acid

A. o-Hydrazinobenzoic acid hydrochloride. In a 2-1. beaker, provided with a stirrer and a low-temperature thermometer, and cooled in an ice-salt bath, are placed 42 g. (0.31 mole) of anthra-nilic acid and 300 ml. of water. The stirrer is started, and 340 ml. of concentrated hydrochloric acid (sp. gr. 1.18) is added in one portion the anthranilic acid dissolves, and its hydrochloride begins to separate almost immediately. After the mixture has been cooled to 0°, a solution of 21.6 g. (0.31 mole) of technical sodium nitrite in 210 ml. of water is added from a dropping funnel, the tip of which extends below the surface of the suspension, at such a rate that the temperature never rises above 3°. The addition requires about 30 minutes stirring is continued for 15 minutes longer, and at the end of this period a positive test with starch-iodide paper should be obtained (Note 1). The dear brown solution is then diluted with 150 ml. of ice water. 

B. Inda2olone. In a 2-1. round-bottomed flask to which a reflux condenser is attached are placed 47.1 g. (0.25 mole) of o-hydrazinobenzoic acid hydrochloride, 1.25 1. of water, and 12.5 ml. of concentrated hydrochloric acid (sp. gr. 1.18). The mixture is refluxed for 30 minutes. The resulting pale yellow solution is transferred in two portions to a 23-cm. evaporating dish and concentrated on the steam bath to about one-fourth its original volume. The indazolone separates at an early stage of the evaporation but redissolves as the concentration of add increases. Sodium carbonate is added to the warm solution in small portions until the acid is neutralized (Note 6), and the suspension is allowed to stand for 2 hours. The nearly colorless indazolone is removed by filtration, washed with two 25-ml. portions of cold water, and air-dried. The yield of product, m.p. 246-249°, is 30-33 g. (90-98%) (Note 7). 

Small amounts of a red crystalline solid wtre obtained at this point by the checkers in several runs. This substance can be converted to o-hydrazinobenzoic acid by the addition of 5 ml. of concentrated hydrochloric acid to a suspension of 1 g. of the solid in 25 ml. of dilute (1 1) hydrochloric acid. The red solid changes to the white o-hydrazinobenzoic acid hydrochloride without apparent solution. 

The free acid may be obtained by treatment of a solution of the hydrochloride with a concentrated aqueous solution of sodium acetate. The powdered hydrochloride (18.9 g., 0.1 mole) is dissolved in 567 ml. of water, and sodium acetate solution (8.2 g. [0.1 mole] of anhydrous sodium acetate in 30 ml. of water) is added. o-Hydrazinobenzoic acid separates at once the mixture is chilled, and the light tan acid is removed by filtration, washed with two 25-ml. portions of water, and air-dried. The yield is 13.1 g. (86%) m.p. 248-2.50°. If a purer acid is required, the crude material may be recrystallized from ethanol (SO ml. per g.) the pale tan product then melts at 250-251.5°. 

Treatment of the N-cyano-imidates (257) with o-hydrazinobenzoic acid gives triazolo[l,5-a]quinazolines (258). The hydrazine attacks the imidate carbon initially, rather than the nitrile group this contrasts with the preferential reaction at the nitrile function of the similar A -cyano-amidines (221) by amines (see p. 253) (Scheme 103). ... 

A mixture of o-hydrazinobenzoic acid hydrodiloride, ethyl 2-cyano-3-ethoxy-acrylate, ethanol, and water heated 10 min. on a steam bath, and allowed to stand overnight at room temp. ethyl pyrazolo[l,5-a]quinazolin-5(4H)-one-3-carboxylate. Y 85%. F. e., also with amino and cyano in place of alkoxy leaving groups, s. J. B. Wright, J. Heterocyclic Chem. 6, 947 (1969). 

Iodine in the benzene nucleus is sometimes removed by hydrazine through replacement or reduction from ethyl 3-iodo-2-naphthoate and hydrazine, /3-naphthoyl hydrazide is obtained. Ethyl p-iodobenzoate yields p-iodobenzhydrazide, but ethyl o-iodobenzoate yields the internal hydrazide of o-hydrazinobenzoic acid. ... 

E.A. Pereira, M.O.O. Rezende and M.F.M. Tavares, Analysis of low molecular weight aldehydes in air samples by capillary electrophoresis after derivatization with 4-hydrazinobenzoic acid, J. Sep. Sci., 27, 28-32, 2004. 

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