Diazotization of 2-aminobenzoic acid

B. Diazotization of 3,5-dichloro-2-aminobenzoic acid. Fifty grams (0.24 mole) of 3,5-dichloro-2-aminobenzoic acid is dissolved in a solution of 12 g. (0.3 mole) of sodium hydroxide in 700 ml. of water. To this solution is added 20 g. (0.29 mole) of sodium nitrite, and the solution is cooled to 10° (Note 5). One hundred milliliters of concentrated hydrochloric acid (sp. gr. 1.191) and 200 ml. of water are placed in a 2-1. three-necked flask and cooled to 10°. The cold solution of sodium 3,5-dichloro-2-aminobenzoate and sodium nitrite is then added to the hydrochloric acid solution with cooling (10°) and efficient stirring at such a rate that no appreciable accumulation of undiazotized amine results (Note 6). At the conclusion of the diazotization, the resulting solution is stirred a few minutes with 2 g. of diato-maceous earth and filtered by suction (Note 7). 

In Chapter 23 we met the remarkable intermediate benzyne and mentioned that convincing evidence for its existence was the trapping by a Diels-Alder reaction. An ideal method for generating benzyne for this purpose is the diazotization of anthranilic acid (2-aminobenzoic acid). 

Iodobenzoic acid has been prepared by the oxidation of -iodotoluene with chromic acid mixture 1 and with nitric acid 2 from the nitrile obtained from -iodonitrobenzene and potassium cyanide 3 and from / -aminobenzoic acid by diazotization.4... 

C) Preparation of o-Chlorobenzoic Acid (Sm.). Use the same method as in sections (A) or (B) above. For diazotization use 4.2 g of o-aminobenzoic (anthranilic) acid and the same quantities of all other reagents. After the decomposition of the diazonium salt the solution is cooled, and the o-chlorobenzoic acid crystals which sep-... 

In the preparation of 2,4,6-tribromobenzoic acid from m-aminobenzoic acid, this substance (0.2 mole) is brominated in solution in dilute hydrochloric acid and the tribromo compound which precipitates is collected and washed and used in the next step without drying. A diazotizing solution is prepared by stirring with ice... 

In a 5-I. round-bottomed flask are placed 165 g. (i mole) of ethyl -aminobenzoate (Coll. Vol. i, 235), 300 cc. of water, and 204 cc. (2.5 moles) of concentrated hydrochloric acid (sp. gr. 1.19) (Note i). This mixture is warmed on a steam bath for an hour with occasional shaking. The flask containing the resulting white paste of -carbethoxyaniline hydrochloride is placed in an ice-salt bath and cooled to 0°. The mixture is stirred mechanically, and a solution of 72.6 g. (i mole) of 95 per cent sodium nitrite in a minimum quantity of water is run in slowly while the temperature is kept below 7°. The diazotization is complete when a faint positive test for nitrous acid with starch-iodide paper persists for ten minutes. 

Dihydro-4-oxo-l,2,3-benzotriazin-3-ylbenzoic acids 212 were synthesized by diazotization of the amino amides 213, obtained by the condensation of the anhydrides 1 and 10 with aminobenzoic acids (214) [128],... 

Aminothiophene-2-carboxylic acid has been diazotized with isoamyl nitrite to form the diazo-nium salt which, on thermolysis, loses CO2. The resultant diazonium salt has been coupled with 2-naphthol. Similarly, 3-aminobenzo[i)]thiophene-2-carboxylic acid has been converted to the corresponding diazonium salt. This preferential loss of CO2 from or/Ao-diazonium carboxylates is unprecedented <89TL2345>. 

It has been found by experiment that substances of the type RX, containing two different haptenic groups, do not form precipitates with either anti-R serum or anti-X serum Alone, but do form precipitates with a mixture of the two specific antisera. This provides proof of the effective bivalence of the dihaptenic precipitating antigen, and thus furnishes further evidence for e framework theory of antigen-antibody precipitation. In these experiments tiie anti-R serum and anti-X serum were made by injecting rabbits with sheep serum coupled with diazotized p-arsanilic add and diazotized p-aminobenzoic acid, respectively, and the RX substances used were l-amino-2-/>-(p-azophenylazo)-phenylarsonic acid-3,6-disul-fonic add 7-p-(p-azophenylazo)-benzoic acid-8-hy-droxynaphthalene and l,8-dihydroxy-2-/>-azo-phenylarsonic acid-3,6-disulfonic acid-7-p-(p-azo-phenylazo)-benzoic acid-naphthalene. 

Diazo coupling—Under conditions where 2-picoline failed to react with diazotized sulphanilic acid or / -aminobenzoic acid, diazotized / -nitroaniline gave 7 per cent of pyridine-2-aldehyde j -nitrophenylhydrazone2i3. In acetic acid containing sodium acetate, the yield i s 58 per cent. Pyridyl-2-acetic acid and its homologues take part efficiently in the Japp-Klingemann... 

The 5-acetyl derivative of (538) has been converted into the 5-NHj, 5-CO2H, and 5-CH2C02H compounds. From the amino-compound the 5-bromo-derivative was obtained upon diazotization, which upon treatment with potassium amide in liquid ammonia gave a mixture of the 4-amino-(major) and 5-amino-isomers. The compound (538) was converted into the iST-oxide, which upon nitration in sulphuric acid gave 4-nitrothieno-[2,3-Z>]pyridine 7-oxide. Nitration in acetic acid, on the other hand, gave the isomeric 5-nitro-derivative. Several reactions were carried out with these nitro-compounds. In a manner similar to that described for (538) and (539), the compounds (542)—(544) were prepared from 3-aminobenzo[6]-thiophen, 2-aminothieno[2,3- ]thiophen, and 5-aminobenzo[6]thiophen... 

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