SU486022A1 - The method of obtaining choline esters of phosphorous acid - Google Patents

Description

one

The invention relates to the field of production of organophosphorus compounds, namely to a method for producing new choline phosphate esters of the general formula

1 (СНз) ЗМ-СН, СН, 0 |, Р-Н,

.

Where; R --- K (S11z) 2 or

-OCH, CH, K (CH3) s;

BUT

And - anion of an acid.

These compounds can be used in biological studies.

Acetylcholine analogs are widely used in studies of the mechanism of excitation transfer from nerve fiber to muscle. So the phosphorylcholines successfully use to study the structure of the active center of cholinesterase.

It is known that the inhibition of this enzyme by the action of organophosphorus compounds consists in the phosphorylation of hydroxyl serine, which is included in the esterase point of cholinesterase.

Choline esters of phosphoric and thiophosphoric acids are known as physiologically active BeaiecTBa.

Tricholine phosphate is obtained by the interaction of trimethylamine with tris (p-chloroethyl) phosphate.

Tricholine ester of thiophosphoric acid was synthesized by the reaction of phosphorus thiochloroxide with p-dimethylaminoethanol alcoholate followed by iodmethylation of the resulting thiophosphate.

Choline phosphate esters are not described in the literature. The method of their preparation is based on the known reaction of phosphorous amides with alcohols, which, however,

not previously used for the synthesis of similar compounds.

By the proposed method, choline chloride is subjected to interaction with hexamethyltriamide phosphorous acid when heated. Depending on the ratio of the initial reagents and the temperature of the process, di- or tricholine phosphate esters are obtained. In the preparation of dimethylamidophosphorous acid dicholone ester, the process is carried out at 110-115 ° C. Upon receipt of tricholinic phosphate ester, the process is carried out at 150 ° C. Target products are isolated.

tricks. It is convenient to distinguish them as perchlorate. For this purpose, the technical product is dissolved in alcohol in cold and a small excess of perchloric acid is added, the precipitated crystals are separated and dried under vacuum while heating.

Example 1. Dimethylamidophosphorous acid dicholone ester.

1.8 g of dry choline chloride and 8.95 g of phosphoric acid hexamethyltriamide are placed in a reaction flask equipped with a reflux condenser with a calcium chloride tube. The mixture is heated, stirred on a magnetic stirrer for 3 hours at-115 ° C. Notable gas evolution in the form of bubbles is observed already at 90 ° C. At the end of the reaction, unreacted amide is separated, the residue is washed with ether and dried in a Fisher pistol.

Obtain 2.14 g (94%) of the desired product in the form of white very hygroscopic crystals.

Found,%: C 39.63; H 8.64; N 12.12.

Ci2H32Cl2N302P.

Calculated,%: C 40.09; H 9.09; N 11.93.

Example 2. Tricholinic phosphate ester.

In Example 1, 1.36 g of dry choline chloride and 3.3 g of phosphoric acid hexamethyltriamide are heated at 140-150 ° C for b-8 hours. At the end of the reaction, the excess amide is removed, the residue is dissolved in 5 ml of ethyl alcohol, filtered through a glass filter, and 1 g of 70% HClO4 is added in the cold. After 4 hours, the precipitated crystals were separated by filtration and treated as in Example 1.

0.76 g (36.5%) of white crystalline matter is obtained; m.p. 149-153 ° C. Found,%: C 28.00; P 6.71; N 6.75. CisHssCUNaOisP. Calculated,%: C 28.01; H 6.10; N 6.57.

Prev Invention

Claims (3)

1. The method of obtaining choline esters of phosphorous acid obsh, her formula (SNZ) zM-CH, CH, OP-N BUT where R is M (CH3) 2 or —OCH, CH, H (CH3), BUT And the acid anion, characterized in that choline chloride is reacted with phosphoric acid hexamethyltriamide when heated, followed by isolation of the desired product using known techniques. 2. A method according to claim 1, characterized in that, in the preparation of dimethylamidophosphorous acid dicholine ester, the process is carried out at PO-115 ° C. 3. A method according to claim 1, characterized in that, in the preparation of phosphorous tricholine ester, the process is carried out at 150 ° C,