Method of producing m-chlorobenzophenone

FIELD: chemistry.

SUBSTANCE: m-chlorobenzophenone is used as an intermediate product in synthesis of original anticonvulsant "halodif" (m-chlorobenzhydrylurea). The method involves diazotisation of 2-amino-5-chlorobenzophenone at room temperature using p-toluenesulfonic acid and polymer diazotising agent, with subsequent treatment of the obtained diazonium tosylate with an aqueous solution of sodium hypophosphite.

EFFECT: method allows for obtaining target product with quantitative output.

6 ex

The invention relates to the field of organic chemistry, in particular to a method for producing m-chlorobenzophenone, which is an intermediate product in the synthesis of the original anticonvulsant "galadir" (m-chlorobenzylamino) [SU 1401842 A1, SS 127/19, SU 1833611 A3, SS 275/24] formula:

With₇H₉lO

We propose a method of obtaining m-chlorobenzophenone the deamination of 2-amino-5-chlorobenzophenone using polymer diastereomer agent.

The use of this method allows to carry out the process at room temperature with a quantitative yield of m-chlorobenzophenone.

Closest to the claimed invention is a method of obtaining m-chlorobenzophenone [SU 1836322, SS 49/813, 45/46, publ. 1990], which consists in the processing of 2-amino-5-chlorobenzophenone with sodium nitrite in aqueous hydrochloric acid at a temperature of 0°C to obtain the corresponding chloride page, which is then treated with an aqueous solution phosphonoacetate sodium at a temperature of 20-30°C, at a molar ratio of 2-amino-5-chlorobenzophenone: sodium nitrite: hydrochloric acid: posterolaterally sodium, equal 1:(0,11-0,13):(0,6-0,8):(0,6-0,8).

The disadvantages of the method on the prototype are:

the use of a large excess of strong mineral acids;

the formation of unstable chloride, page, h is about requires it quickly in the further transformation;

the complexity of the technological process due to the need to maintain the temperature of the diazotization reaction at 0°C;

the use of special equipment associated with providing cooling of the reaction mass under diazotization;

the selection side of harmful nitrogen oxides even at small temperature deviations.

Technical problem behind the present invention is to obtain m-chlorobenzophenone of 2-amino-5-chlorobenzophenone method leselinyana through the reaction of diazotization.

The goal of the project is achieved by the fact that in the proposed method of obtaining m-chlorobenzophenone uses a new approach for conducting the reaction of diazotization using polymer diastereomer agent, p-toluenesulfonic acid instead of mineral hydrochloric acid, resulting in a corresponding stable toilet the page at room temperature.

As the polymer diastereomer agent encouraged to use strong basic anion exchange resin curing type, which are copolymers of styrene and divinylbenzene, with a grain size of 0.4 to 1.2 mm and a volumetric capacity of 0.1 N. the Hcl solution for at least 2 mmol/g

Example 1.

To obtain m-chlorobenzophenone the proposed method has preliminarily the prepared polymer diasterous agent. To do this, in a reactor equipped with a stirrer, was loaded with 50 ml of water, 5.4 g of sodium nitrite, 15 g of anion exchange resin brand AV-17-8. The resulting reaction mass is stirred for 10 minutes, after which the formed polymer diasterous agent is filtered off, washed on the filter with water, bringing the pH up to neutral reaction, and is used in the diazotization of 2-amino-5-chlorobenzophenone. Thus prepared polymer diasterous agent is the concentration of NO⁺cations of 1.05 mol/L.

In a reactor equipped with a stirrer, was loaded with 50 ml glacial acetic acid, 13.5 g of the monohydrate of p-toluenesulfonic acid. The reaction mass is stirred until complete dissolution of p-toluenesulfonic acid for 2-3 minutes at room temperature. Then under stirring load the previously obtained polymer diasterous agent and portions of 4.2 g of 2-amino-5-chlorobenzophenone. The reaction mass is stirred for 30 minutes at room temperature, the resulting solution tosilata the page in acetic acid. The end reaction of diazotization determined by TLC (eluent benzene: ethanol = 9:1). After completion of the diazotization reaction solution tosilata the page is filtered from the anion exchange resin. In the resulting solution tosilata the page in acetic acid under stirring once poured freshly prepared aq is th solution phosphonoacetate sodium (10 g NaH ₂PO₂in 10 ml of N₂About). The reaction mass is stirred for 6-7 hours at room temperature before the end of the reduction reaction of that control on the sample with β-naphthol (no redness). Then the reaction mass is poured 50 ml of water, stirred for 5 minutes. The precipitate is filtered off, washed with 100 ml of water, treated with 20 ml of 2%aqueous solution of acid sodium carbonate, washed with water, bringing the pH up to neutral reaction, dried, recrystallized from petroleum ether and obtain 3.7 g (99%) m-chlorobenzophenone with a melting point of 83-84°C; IR spectrum (liquid paraffin): γ=1660 cm^-1, R_f=0,9.

Example 2.

Differs from Example 1 in that instead of the anion brand AV-17-8 in obtaining polymer diastereomer agent use the same number Amberlit IRA 402. The yield of the final product m-chlorobenzophenone was 99%.

Example 3.

Differs from Example 1 in that instead of the anion brand AV-17-8 in obtaining polymer diastereomer agent use the same number Amberlit IRA 410. The yield of the final product m-chlorobenzophenone was 99%.

Example 4.

Differs from Example 1 in that instead of the anion brand AV-17-8 in obtaining polymer diastereomer agent use the same number Amberlit IRA 900. The yield of the final product m-chlorobenzophenone was 99%.

Example 5.

The difference is between a of Example 1, however, instead of the anion brand AV-17-8 in obtaining polymer diastereomer agent use the same amount of Amberlyst A-15. The yield of the final product m-chlorobenzophenone was 99%.

Example 6.

Differs from Example 1 in that instead of the anion brand AV-17-8 in obtaining polymer diastereomer agent use the same amount of Amberlyst A-26. The yield of the final product m-chlorobenzophenone was 99%.

The claimed method of obtaining m-chlorobenzophenone can be used in chemical and pharmaceutical industry in the synthesis of the original anticonvulsant "galadir" (m-chlorobenzylamino).

The method of obtaining m-chlorobenzophenone by diazotization of 2-amino-5-chlorobenzophenone at room temperature using p-toluenesulfonic acid and polymer diastereomer agent with subsequent processing of the received tosilata, page aqueous solution phosphonobutane acid sodium.