SU12600A1 - The method of preparation of barbituric acid derivatives - Google Patents

Description

The proposed method for the preparation of barbituric acid derivatives of the general formula

, f, .. f. - CO-NH /

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where B is an unsaturated aliphatic residue, a -and, and E, are two different aliphatic, aromatic, or ali-radicalic residues, the fact is that an unsaturated aliphatic residue is introduced into monosubstituted barbituric acids containing a CH residue. It is also possible to achieve the production of the same barbituric acid derivatives from CH containing malonic esters, then entering into them an unsaturated aliphatic residue. The resulting barbituric acid derivatives have more or less hypnotic properties.

The production of these derivatives occurs when applying methods generally accepted for the extraction of barbituric acids with two carbon atoms substituted in them. For the purpose of introducing a -haloaryl residue, it is not necessary to use at least 1,2-dibromo-2,3-bromo ropen: with appropriate addition of alkali we can proceed from 1. 2, 3-trihalopropane.

Example 1. Prepared in the usual manner from 69 parts by weight of sodium, 690 parts by volume of absolute alcohol and 216 parts by weight of diethyl ether of a secondary bottle of lamajonic acid (boiling point 115-116 °, 12 mm: D5 0.988), by condensation with 90 weight parts of urea and precipitated from the initially formed sodium salt, after evaporation of the alcohol and dissolving in 750 volume parts

water, by supersaturation with 300 parts by volume of hydrochloric acid (1.19), the secondary butylbarbituric acid crystallizes out of the water in the form of silvery-shiny leaves with a melting point of 194-195 °.

184 parts of this acid are dissolved in 40 parts of NaOH containing diluted sodium alkali. 1x 127 parts of allyl bromide are added to the bright solution and the mixture is heated by stirring for several hours to 55-60 °. The oil-like reaction product, which is precipitated by heating and cooling, solidifies into a solid, white, crystalline mass, which, when rubbed with a small amount of water, disintegrates into a fine powder; this powder is sucked off and washed with water. The resulting, in a quantity that almost exactly corresponds to the theoretical yield, secondary butylgilyl-barbituric acid, after non-recrystallization from chloroform, shows a melting point of 109-110 °. It is easily soluble already in the cold; in alkalis, alcohol, ether, acetone, or lightly heated, it is well soluble in water, benzene, chloroform; in netrole ether, even heating is hardly soluble.

Example 2. 184 parts of secondary buty. 1-barbituric acid (melting point C) dissolve in 500 parts by volume in 2-sodium alkali and are thoroughly nonreactive with 205 parts of 2, D) dibromopro-ian (-1) at a new temperature. during few hours. The isolated, as a semi-solid mass, the reaction product is extracted in the heat with a small amount of x. Doform. The reaction product is thus obtained in the form of fine, colorless crystals which, by recrystallization from water or from diluted acetic acid, are isolated in pure form. Secondary butyl - omally-barbituric acid has a melting point of. It is already easily soluble in the cold in alcohol, ether, acetone, benzene, toluene, and acetic acid.

ether, glacial acetic acid, is more difficult to dissolve in water, hexahydrotoluene, chloroform, mail is insoluble in petroleum ether.

Example 3. A solution of sodium ester ether from 4.4 parts of Na, 60 parts by volume of alcool and 31 parts of malonic ester is boiled with 38 parts of iodine-tepentane for 6 hours with a reverse set fridge in a water bath. The alcohol is then distilled off, the residue is dissolved in water, extracted with ether and dried over. To distill off the ester, methyl-and-nropyl-methylmalonic ether boils in vacuum (13 mm) at 122-125 °.

To an alcoholic solution of 9.9 parts of Na in 120 parts by volume of alcohol (absolute), 12.4 parts of urea and 33 parts of methyl and prone methyl methyl ester are added and the whole is heated for 6 hours in a water bath. . By distillation, the alcohol is dissolved in water; Methyl-p -nopropyl-methi-1-barbituric acid is precipitated from the aqueous solution with dilute hydrochloric acid and, after drying, is recrystallized from acetic acid by a fortress about its melting point 162-163 °.

38 parts of methyl - "- ipropyl - methyl barbituric acid, dissolved in 120 parts by volume of 6.6 /" aqueous sodium alkali, are heated with 40 parts of m-bromoallyl - bromide for approximately one day, stirring the mixture at 70- 80 °. The methyl-and-pronnl-bromo-allyl-barbituric acid crystallized on cooling is sucked off and precipitated from the diluted alkaline solution after filtration; non-recrystallized from slightly diluted glacial acetic acid, it is melted to nrn 164-165 °; acid is soluble in most organic solvents.

The subject of the patent. The method of preparation of barbituric acid derivatives of the general formula

-K ../ C0-yV E, R. CH / CO - NH /

-B means an unsaturated aliphatic residue, a, and J2, j are two different aliphatic, aromatic or alicyclic residues, characterized in that monosubstituted barbituric acids containing a CH residue are added

With conventional methods, the limiting alfatic residue, or malonic esters containing the residue jR, 2 SI, is converted into barbituric acid derivatives, into which the unsaturated aliphatic residue is then introduced.