The method of obtaining 1,4 : 3,6-dianhydro-d-sorbitol

 

(57) Abstract:

The invention relates to the technology of 1,4 : 3,6-dianhydro-D-sorbitol (sorbed, isosorbide), which is an intermediate in the production of medicines on the basis of its mono - and dinitropropane, which is used as a vasodilator prolonged action in hypertension, angina and other cardiovascular diseases. Describes how to obtain carbide, which consists in boiling when 130-150oWith food sorbitol in the medium of xylene with water separator until the cessation of water separation in the presence as catalyst p-toluenesulfonic acid, taken in an amount of 5.0% by weight of sorbitol. The technical result consists in simplifying the process and increasing the yield of the target product, while maintaining its high quality. table 2.

The invention relates to the technology of 1,4:3,6-dianhydro-D-sorbitol (sorbed, isosorbide), which is an intermediate in the production of medicines on the basis of its mono - and dinitropropane, which are used as a vasodilator prolonged action in hypertension, angina and other cardiovascular SV acid type scheme

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There are several ways to get isosorbide, however they mostly have only laboratory value, their implementation in an industrial environment is difficult due to the high cost and complexity of the process.

The most noteworthy ways dehydration of sorbitol in toluene or xylene in the presence of acid catalysts nature [1-3]. According to these works, the output isosorbide ranges from 8 to 67%. Methods for isolation and purification of isosorbide complex, long and multi-stage.

Currently isosorbide get improved method proposed by P. M. Kochergin with employees [4, 5]. This method is implemented in Krasnouralsk copper smelting plant in Krasnouralsk the Ekaterinburg region) and adopted us for the prototype.

In this way isosorbide is obtained by boiling at 130-150oC food sorbitol in the medium of xylene with water separator until the complete termination of water (about 8 h) in the presence as catalyst p-toluenesulfonic acid, taken in an amount of 5.0% by weight of sorbitol.

So, 2.0 kg of the crushed food sorbitol take 7.5 l technical xylene and 100 g of p-toluenesulfonic acid. The reaction water is collected in the water separator. On iconastas dark residue is dissolved in 10 l of water and boil 1,0 h with 0.5 kg of activated carbon, then the solution is cooled to 50-60oC and filtered from coal. The filtered coal boiled for 1 h with 2.0 l of water for a more complete extraction of isosorbide and filtered. From United almost colorless filtrate water is distilled off in a vacuum at a temperature not higher than 75,0oC. a Thick residue (about 1.5 kg) of isosorbide raw cleanse by deep-vacuum distillation (pressure of 1.0 to 4.0 kPa, the temperature in pairs 160-175oC).

Isosorbide is obtained as a pale yellow oil that crystallized upon standing or making seed yield 68-70% of theoretical.

The advantage of this process is that sorbed get high quality and for further processing there is no need for additional recrystallization him from flammable solvents.

The disadvantages of the method are:

- a multi-stage process;

- use GZH as the reaction medium, which makes the process of fire;

high labour and energy cost;

- the use of a large number of scarce catalyst and activated carbon (in 5.0 and 25.0 wt.% respectively);

- poor performance.

According to the authors [4, 5] and patent [3] decrease if the littelest reaction of dehydration.

The aim of the present invention is

- creation of a single-stage, high-performance, fire-get isosorbide;

- eliminate labor intensive and energy-intensive stages;

- reduce consumption of raw materials;

- increase the yield of the target product, while maintaining its high quality.

This goal is achieved by combining the processes of dehydration food carbide and purification of the resulting isosorbide.

Distinctive features of the method is that the process of dehydration is carried out with simultaneous separation from the reaction zone of the target product and the reaction water. The reaction is carried out in the presence of catalytic amounts of water (3-10 wt.%) and acid catalyst (0.2 to 0.6 wt.% p-toluenesulfonic acid or sulfuric ortho-phosphoric acid).

The process is performed at a pressure of 1.0 to 4.0 kPa, which corresponds to the boiling temperature of the reaction mass 165-195oC, but not above 205oC because at this temperature already has a partial resinification of the reaction mass, resulting in a loss of yield of the target product. For the criterion of the process is the vacuum (or residual pressure), which determines the boiling point (othonna, equipped with a thermometer, was loaded 75,0 g food sorbed (in terms of 100%), of 0.15-0.45 g of catalyst and 2.25-7,50 ml of water. The flask through the nozzle vyurts connected with receiver isosorbide connected through a cooler-condenser with a collection of water that connects to a vacuum pump. The reaction mass was heated on a sand bath under vacuum. Thus the boiling temperature of the reaction mass was 170-195oC. When this temperature was held for selection of isosorbide in the form of a light yellow oil that crystallized upon standing or when making seed. The reaction water passing through the collector isosorbide, was condensed in the cooler-condenser and collected in the water collection.

On the technological regime in the laboratory were developed samples of isosorbide, of which, after nitration was obtained 2,5-dinitrate treatment-1,4:3,6-dianhydro-D-sorbitol with a good solution that meets the requirements of the Federal Assembly of 42-422-86.

The results of the experiments are presented in table.2, which shows that the isosorbide is obtained from the output 70,6-78,1%. The quality of isosorbide was evaluated by gas chromatography. Found that the quality of isosorbide received by existing and proposed technology, islanova catalyst at elevated temperature, characterized in that, to simplify and enhance the security of the process and increase the yield of the target product as the acid catalyst used p-toluensulfonate, phosphoric or sulphuric acid taken in the quantity of 0.2 - 0.6 wt.%, and the process is carried out in the presence of 3.0 - 10.0 wt.% water at a temperature of 165 to 195oC and a pressure of 1.0 to 4.0 kPa (-0,96oC -0,99 kgf/cm2with simultaneous distillation of the water and the desired product from the reaction zone.

 

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