RU2708590C1 - Method of purifying glycoluril from hydantoin impurity - Google Patents

Abstract

FIELD: manufacturing technology.

SUBSTANCE: invention relates to methods of purifying substances from related hardly-separable impurities by crystallization, specifically to a method of purifying glycoluril (2,4,6,8-tetraazabicyclo[3.3.0]octane-3,7-dione) from hard-separable impurities of hydantoin (2,4-imidazolidinedione), wherein hydantoin is formed as a by-product (product of condensation of urea and glyoxal at high temperature in acidic medium) and content thereof should not exceed 0.1 %. Method of purifying glycoluril from admixture of hydantoin to hydantoin level of less than 0.1 % involves applying a crystallization method by successively dissolving glycoluril with a hydantoin admixture in 85 % orthophosphoric acid while heating to 60 °C, cooling the obtained solution to room temperature and adding acetonitrile in ratio, pts. wt.: glycoluril with a hydantoin impurity of 1, 85 % orthophosphoric acid 5, acetonitrile 4, followed by washing the residue with acetonitrile, filtering and drying.

EFFECT: disclosed is a method of purifying glycoluril from hydantoin impurities.

1 cl, 1 dwg

Description

The invention relates to methods for purifying substances from related hardly separated impurities by crystallization. The invention consists in a method for the purification of glycoluryl (2,4,6,8-tetraazabicyclo [3.3.0] octane-3,7-dione) from an intrinsic impurity of hydantoin (2,4-imidazolidinedione). Hydantoin is formed as a by-product in the synthesis of glycoluril (as a condensation product of urea and glyoxal at elevated temperatures in an acidic environment). The analysis of glycoluril samples obtained from urea and glyoxal synthesis shows that they contain 1–2% hydantoin impurities. Moreover, in glycoluril, intended for the synthesis of supramolecular compounds (cucurbituril and bambusuril), affinity sorbents and substances of high purity, the content of hydantoin should not exceed 0.1%.

The content of hydantoin impurities in glycoluril can be determined by high performance liquid chromatography (HPLC) according to our developed method. About 40 mg (accurately weighed) of glycoluril is dissolved by heating in a water bath in 30 ml of water, the resulting solution is quantitatively transferred to a volumetric flask with a capacity of 50 ml, the volume of the flask is adjusted to the mark with water. 20 μl of the obtained test solution was chromatographed using an UltiMate 3000 HPLC liquid chromatograph with a spectrophotometric detector, wavelength 195 nm, flow rate 1.0 ml / min, ACE Excel 3 C column ₁₈ 250 × 4.6 mm, column temperature 50 ° C. Then chromatograph 20 μl of the comparison solution (0.1% aqueous hydantoin solution). The hydantoin content is calculated by a single point calibration method.

A known method of producing glycoluryl by condensation of glyoxal and urea at a temperature of 80 ° C in the presence of p-toluenesulfonic acid [1]. Purification of the product is carried out by cooling the reaction mixture, filtering the precipitate on a Buchner funnel, washing with water and drying.

A method for producing glycoluril by the interaction of urea with an aqueous solution of glyoxal at 85–90 ° C in hydrochloric acid at pH = 1.5–2.0 is described [2]. The purification process of glycoluril in this method is not shown.

A known method by condensation of glyoxal and urea at a temperature of 80 ° C in the presence of sulfuric acid. After the reaction, the mixture is cooled to room temperature, the precipitate is filtered off, washed with water, dried [3].

The disadvantage of all of the above methods is the presence in the glycoluril impurities of hydantoin in a concentration of 1-2%. The present invention is to develop a method for the purification of glycoluril from impurities of hydantoin.

The technical result of the invention is the reduction of the content of hydantoin impurities in glycoluril to a level of less than 0.1%.

The purification of glycoluril from hydantoin by the method of “classical” recrystallization from hot water is characterized by low efficiency due to the close solubility of glycoluril and hydantoin. Glycoluryl is practically insoluble in alcohols, alkanes, ethers, acetone, toluene and chloroform even when heated, so its recrystallization from these solvents is impossible.

The problem is solved by crystallization of glycoluril from a solution of 85% phosphoric acid with the addition of acetonitrile. We found that orthophosphoric acid has a high solubility in relation to glycoluril - more than 150 g / l. A solution of glycoluryl in phosphoric acid is prepared in a mass ratio of 1:10 at a temperature of 60 ° C in order to accelerate the process. Precipitation of pure glycoluril occurs when a small volume excess of an aprotic solvent, acetonitrile, is added to the cooled glycoluril phosphoric acid solution, while the solubility of glycoluril is significantly reduced, and hydantoin remains in the solution. Glycoluryl precipitates in the form of needle crystals. The resulting precipitate of purified glycoluril is separated from the solution by filtration, washed with acetonitrile and dried. Glycoluryl purified in this way contains less than 0.05% hydantoin.

In FIG. 1. The chromatograms of glycoluril samples are presented: a — initial sample; b - sample after cleaning.

The following is an example of a specific embodiment of the invention.

Example - obtaining purified glycoluryl

1 g of the starting glycoluryl containing 1.6% hydantoin (Fig. 1 a) was dissolved in 5 g of phosphoric acid when heated in a water bath at 60 ° C. After cooling, 5 ml (about 4 g) of acetonitrile was added to the resulting solution. The precipitate was filtered off and dried by heating in an oven. Received 0.6 g of purified glycoluryl. The content of hydantoin in glycoluril was less than 0.05% (Fig. 1 b).

Literature

1. Pat. No. 2583110 of the Russian Federation, IPC C07D 487/04. A method of producing glycoluril / Malkov V.S., Odysheva L.E. Application 2014152624/04 of 12.25.2014, publ. 05/10/2016 Bull. Number 13.

2. Slezak F.B., Hirsch A., Rosen I.J. Halogenation of glycoluril and diureidopentane // J. Org. Chem., 1960. - Vol. 25 (4). - pp. 660–661.

3. Pat. No. 2439072 of the Russian Federation, C07D 487/04. The method of obtaining 2,4,6,8-tetraazabicyclo [3.3.0] octane-3,7-dione. Malkov V.S., Knyazev A.S., Volynets A.A. Application 2010123595/04 dated 06/09/2010, publ. 01/10/2012 Bull. Number 1.

Claims (3)

The method of purification of glycoluril from hydantoin impurities to a hydantoin content of less than 0.1%, which consists in applying the crystallization method by sequentially dissolving glycoluril with hydantoin in 85% phosphoric acid while heating to 60 ° C, cooling the resulting solution to room temperature and adding acetonitrile to ratio, mass. parts: hydantoin glycoluryl one 85% phosphoric acid 5 acetonitrile 4 followed by washing the precipitate with acetonitrile, filtering and drying.

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