NO130345B - - Google Patents

Description

Process for the production of sedative-acting phenyl-alkyne-diols.

The present invention relates to a

process for the production of sedative-acting phenyl-alkyne diols with the general formula:

in which R represents hydrogen or a lower alkyl group. By the procedure

according to the invention, these phenyl-alkyne-diols are prepared by reacting 2-phenylacetoin

with an alkyne or a metal compound of

an alkyne, having the general formula

XC = CR, in which X is Li, Na, K, -MgCl,

- MgBr or - MgJ, and R is hydrogen or

a lower alkyl group. When applying

an alkyne is generally required

promoting the reaction by means of an alkaline substance or another known condensation agent for alkynes. When one uses a metal compound of an alkyne, one obtains

one a metal connection if desired

phenyl-alkyl-diol, and this metal compound is then decomposed into the desired one

compound by hydrolysis. If the metal compound used is a magnesium compound, the compound formed is decomposed most appropriately by adding

of an acid.

The compounds produced by the method according to the invention are up to now

unknown substances. They are valuable sedatives.

In experiments with small mammals, it was found that

the substances are capable of exerting long-lasting sedative effects, inducing muscle relaxation and, at larger doses, loss of postural reflexes. Furthermore, they block the polysynaptic reflexes in the spinal cord in cats, but have no effect on the monosynaptic reflexes, on the neuromuscular transmission or on the conduction of the peripheral nerves.

The new substances are to a greater extent than the known sedatives, 2-methyl-2-n-propyl-1,3-propanediol-dicarbamate (meprobamate) and 2-p-chlorophenyl-3-methyl-2,3-butanediol (phenaglycodol ) able to prolong the sleep induced by 1,5-dimethyl-5-(1-methylbutyl)-barbituric acid (hexobarbital), and in this respect they are superior in comparison with 2-phenyl-3-methyl -2,3-dihydroxyhexene-(5) and its p-chloro derivative. Clinical experience has shown that the new substances have a better effect than meprobamate as a sedative for patients who suffer from senile mental disorders, such as depression, confusional states, restlessness and states of agitation.

Example 1.

Sodium acetylide is prepared in a known manner from 9.2 g of sodium dissolved in 500 ml of liquid ammonia and acetylene, and the sodium acetylide solution is cooled to a temperature of between -50° and -40° C. At this temperature, 16.4 g of 2- phenylacetoin while stirring and adding acetylene. The temperature of the reaction mixture is then raised to approx. -30° C, and the ammonia is allowed to evaporate during approx. 10 hours. The residue is poured into ether, and it is then decomposed by the addition of dilute sulfuric acid under cooling. The ether solution is washed with water and dried over MgSC-4. The ether is distilled off and the residue is distilled in vacuo to give 2-phenyl-3-methyl-2,3-dihydroxypentyne- (4) with

boiling point 153-155° C at 15 mm Hg.

Example 2.

In an autoclave equipped with stirrers, a mixture of 82 g of 2-phenylacetoin and 80 ml of a 3% aqueous solution of potassium carbonate is reacted with a mixture of 75% by volume. acetylene and 25 vol. nitrogen at 20 atmospheres pressure and 95° C. The said pressure is maintained by introducing more of the gaseous mixture, until the pressure remains constant and thereby indicates that the reaction is complete. The reaction mixture is then extracted with ether, and the ether solution is dried over MgSO-t. The ether is distilled off and the residue is distilled in vacuo to give 2-phenyl-3-methyl-2,3-dihydroxy-pentyne-(4) with a boiling point of 150-152° C. at 12 mm Hg.

Example 3.

A solution of sodium amide in liquid ammonia is prepared in a known manner from 9.2 g of sodium, 0.15 g of ferric nitrate and 600 ml of liquid ammonia, and the solution is cooled to a temperature of between -50° and -40° C. At this temperature, add 20 g of methylacetylene during 20 minutes with stirring. Stirring is continued for one hour, while the temperature of the reaction mixture gradually rises to approx. -33° C. Now 16.4 g of 2-phenylacetoin is added dropwise while stirring, after which the ammonia is allowed to evaporate during approx. 10 hours. Ether is poured onto the residue, which is then decomposed by the addition of dilute sulfuric acid while cooling. The ether solution is washed with water and dried over MgSC-4. The ether is distilled off, and the residue is distilled in vacuo to give 2-phenyl-3-methyl-2,3-dihydroxyhexyne-(4) with a boiling point of 170-176° C at 14 mm Hg.

Example 4.

To an ethereal solution of ethylmagnesium bromide prepared from 10 g of Mg, 43.5 g of ethyl bromide and 400 ml of absolute ether, a solution, which has previously been cooled to -10° C, of butyne- (l) in 150 ml of absolute ether. The temperature of the reaction mixture is then allowed to gradually rise to 20° C over the course of 48 hours, after which 16.4 g of 2-phenylacetoin are added dropwise over the course of 2 hours with stirring. Stirring is continued for 24 hours, after which dilute sulfuric acid is added while cooling. The ether phase is separated, washed with water and dried over MgSOt. The ether is distilled off, and the residue is distilled in vacuo to give 2-phenyl-3-methyl-2,3-dihydroxy-heptyne-(4) with a boiling point of 173-180° C. at 13 mm Hg.

Claims (1)

Process for the preparation of sedative-acting phenyl-alkyne diols with the general formula in which R is hydrogen or a lower alkyl group, characterized by reacting 2-phenylacetoin with an alkyne or a metal compound of an alkyne, which has the general formula XC = CR, in which X is Li, Na, K, - MgCl, -MgBr or -MgJ, and R is hydrogen or a lower alkyl group.