SU654615A1 - Method of obtaining 5-nitro-8-oxyquinoline - Google Patents

Description

(54) METHOD FOR OBTAINING 5-NITRO-8-OXYHINOLINE

18–40 ° C in the case of organic acids and purification of the target product is carried out with subsequent recrystallization from aqueous alcohol. Sublimation is advantageously carried out by passing a carrier gas of nitrogen through a layer of crushed product from top to bottom at 130-170 ° C, and the precipitation of the freeze-dried product is caused by the supply of cold nitrogen to the hot stream.

The distinctive features of the proposed method is that 8-hydroxyquinoline is first acted upon with dilute nitric acid (sp. Weight 1.345) at 5-10 ° C, and 8-hydroxyquinoline nitrate is acted upon with acid selected from sulfuric, at a temperature of -20. to -14 ° C, formic, acetic or propionic at 35-40 ° C and the target product is purified by sublimation, followed by recrystallization from aqueous alcohol.

The output of 5-nitro-8-hydroxypoline 60-69%.

Example 1. 7.25 (0.05 mol) of 8-hydroxyquinoline are suspended in 15 ml of absolute alcohol, added at 18–20 ° C and transported over 20 min to 6 ml (0.072 mol) of nitric acid (specific weight of 1.345) . The yellow precipitate of nitrate of 8-hydroxyquinoline is filtered off, washed with alcohol.

Yield 9.4 g (90.3%). T. pl. 174.5-175 ° C.

Found,%: C 52.00; H 4.40; N 13.00.

CgHyNO-HNOs.

Calculated,%: C, 51.93; H 3.87; N 13.45.

Example 2. 14.5 g (0.01 mol) of 8-hydroxyquinoline is dissolved in 87 ml of acetic acid, added at 5-10 ° C and transferred 8.32 ml (0.1 mol) of nitric acid (specific weight 1,345) for 5-10 min. The precipitated yellow precipitate of 8-hydroxyquinoline nitrate is filtered off, washed with alcohol, and present.

Yield 17.4 g (83.5%). T. pl. 173-174 ° C. Identical to the product described in Example 1. The IR spectra are identical, the sample does not detect a displacement of the melting point.

Example 3. 21.17 g (0.146 mol) of 8-hydroxyquinoline is dissolved in 100 ml of propionic acid and 13 ml (0.156 mol) of nitric acid (sp. Weight 1.345) are added to the solution at O-5 ° C and constantly moving. . A light yellow precipitate of 8-hydroxyquinoline nitrate is formed immediately, which is filtered off, washed on the filter with absolute alcohol, and is formed. T. pl. 173-174 ° C.

The yield of 28.0 g (92.2%). Identical to the product described in example 1.

Example 4. 20.8 g (0.1 mol) of 8-hydroxyquinoline nitrate are suspended in 62.4 ml of acetic acid, heated to 35 ° C, dissolution of the nitrate precipitate begins with an exothermic effect (the same result can be achieved by adding 1 -1, 5 ml of strong acid: sulfuric, hydrochloric. The reaction mass is cooled and maintained at 35-37 ° C for half an hour, then 500 ml of distilled water is added and 40% sodium hydroxide solution is brought to pH 5. The mixture is kept at 10-15 ° C for half an hour. The precipitated 5-nitro8-hydroxyquinoline precipitate is filtered off, washed with water, and t, suschat at 60- 70 ° C.

Yield 11.91 g (62.7%). The product is subjected to sublimation, and then recrystallization from 80% alcohol. T. pl. 181-181.5 ° C. Found,%: N 14.57. CgHeNsOs.

Calculated,%: N 14.70.

According to thin layer chromatography, the product does not contain impurities and meets all the requirements imposed on the preparation of pharmacopoeial purity. 5-nitro-8-oxyquinoline obtained by the methods described in examples 5-8, purified in example 4 and identified with it according to TLC and IR spectra.

Thin-layer chromatography was carried out on Silufol-254 plates impregnated with a saturated solution of Trilon B, dried and labeled by the Mattis method with a width of 20 mm. The benzene-methanol-dimethylformamide system (24:

: 6: 1).

Example 5. 20 ml of concentrated sulfuric acid are cooled to -20 ° C and in portions with a good displacement, not allowing the temperature to rise higher

-14 ° C, 5.2 g (0.025 mol) of 8-hydroxyquinoline nitrate is added. The resulting thick, black-brown solution is kept for 10 minutes at -14 ° C, then the outer cooling is removed, the temperature is given

solution is raised to 0 ° C and poured into 200 ml of chilled distilled water, neutralized with caustic soda solution to pH 5. When a pH of 2-3 is reached, a bulky precipitate of 5-nitro-8-hydroxyquinoline sulfate is formed, which upon further alkalinization goes into 5-nitro8 oxyquinoline. The latter is filtered off, washed thoroughly on the filter with water, dried at 70 ° C.

Yield 3.27 g (68.8%).

Example 6. 5.2 g (0.025 mol) of 8-hydroxyquinoline nitrate are dissolved at a temperature not higher than 18-20 ° C in 15 ml of formic

acid. The solution is gently heated to 27-28 ° C, the development of the exothermic process of nitrate conversion begins. Cooling, the mass is maintained at a temperature of 32-36 ° C for 30 minutes, then

poured into 200 ml of distilled water, neutralized with a solution of alkali to pH 5. The precipitated 5-nitro-8-hydroxyquinoline precipitate is filtered, washed on the filter with water, and existed at 70 ° C.

Yield 3.03 g (63.8%).

Example 7. 14.5 g (0.1 mol) of 8-oxycinnolina are dissolved in propionic acid cooled to 5 ° C and 8.32 ml (0.1 mol) of nitric acid are added at 5-10 ° C and in good mixing. (sp. weight 1,345). A light yellow precipitate of 8-hydroxyquinoline nitrate falls out. No precipitate is released, the mass is heated to 40-4 ° C, the precipitate of nitrate dissolves, the mass is kept at this temperature for 30 minutes. (The conversion of nitrate can be carried out at 28 ° C, if 2 ml of concentrated sulfuric acid are added to the mass and allowed to stand for 2 hours). The mass is poured into 750 ml of water, alkalinized to RP 5, the precipitate of 5-nitro-8-hydroxyquinoline is filtered off, washed on the filter with water, and dried at 70 ° C

Yield 11.52 (60.6%).

Example 8. 10.4 g of 8-hydroxyquinoline nitrate is added in portions to 40 ml of sulfuric acid so that the temperature does not rise above -20 ° C. After all the nitrate is added, the mixture is kept at room temperature for 2 hours, then poured into 400 ml of chilled distilled water and neutralized with 20% sodium hydroxide to RP 6. The precipitate formed is filtered off, washed with distilled water and washed with 120 ml of acetone. The acetone solution is filtered hot, diluted with 120 ml of water and cooled. A precipitate of 5-nitro-8-hydroxyquinoline is precipitated, which is filtered, dried.

Chrome is 8.1 g (85.20 / 0). Read by sublimation followed by recrystallization from aqueous alcohol, analogously to example 4.

When determining the main content of 5-POC and products before purification using UV-spectroscopy, the following data were obtained,%: in a product obtained from sulfuric acid 70-72; from formic 75- 78; from acetic acid 84-87; Propionic 92-93.

After cleaning, the content of the main ventecTBa 99.7-100%.

Claims (3)

1. The method of obtaining 5-nitro-8-hydroxyquinoline by treating 8-hydroxyquinoline with two acids, one of which is nitric, with the release of the target product, characterized in that, in order to simplify the process technology, increase the yield and improve the quality of the target product, first 8-hydroxyquinoline is treated with dilute nitric acid at 5-10 ° C, the resulting 8-hydroxyquinoline nitrate is acted with an acid selected from sulfuric, formic, acetic or proionic at a temperature of from -20 to -14 ° C in the case of sulfuric acid, at a temperature of 35-40 ° C in case e organic acids and then the desired product was purified by sublimation, followed by recrystallization from aqueous alcohol. 2. A method according to claim 1, characterized in that the sublimation is carried out by passing a carrier gas, nitrogen through a layer of crushed product from top to bottom at 130-170 ° C, and the sublimated product is precipitated by feeding cold nitrogen into a hot stream. 3. A method according to claim 1, characterized in that dilute nitric acid is used with beats. weighing 1,345.