DE1073477B - Process for the production of 2-phenyl- and 2-p-chlorophenyl- 3-methyl-2,3-dihydroxy-hexene- (5) effective as sedatives - Google Patents

Description

The invention relates to a process for the preparation of hitherto unknown 2-phenyl and 2-p-Chlorophenyl-3-methyl-2,3-dihydroxy-hexene- (5) of the general formula

CH ₃
CC-CH ₂ -CH = CH ₂

OH OH

where X is a hydrogen or a chlorine atom.

The process according to the invention is characterized in that 2-phenyl- or 2-p-chlorophenyl-acetoin reacts with 2-propenylmagnesium chloride or bromide, after which the Grignard compound formed to the desired compound and is decomposed to magnesium hydroxychloride or bromide.

The new compounds can be used as sedatives, especially as tranquilizers. In biological experiments with small mammals the compounds have been found to have a long lasting sedative effect exercise and thereby cause muscle relaxation, with larger doses even cause the loss of the stretch reflex. They also create a blockage in the polysynaptic reflexes in cats' spinal cords, they have no effect on the monosynaptic reflexes, on the myoneural connection and on the peripheral nerve conduits.

The new compounds can be compared favorably with known tranquilizers, such as 2-methyl-2-n-propyl-1,3-propanediol dicarbamate and 2-p-chlorophenyl-3-methyl-2,3-butanediol in their prolongation effectiveness of sleep, caused by 1,5-dimethyl-5- (l-methylbutyl) barbituric acid. So in this attempt it has 2-Phenyl-3-methyl-2,3-dihydroxy-hexene (5) about four times as much activity as the carbamate.

Clinical trials have shown that 2-phenyl-3-methyl-2,3-dihydroxy-hexene (5) can be compared favorably with the above-mentioned carbamate as a tranquilizer for male and female patients aged 67 to 89 years suffered from mental senile disorders such as depression, confusion, restlessness, agitation. In 28% of the cases examined a better effect was observed when it was obtained with the carbamate, while in 22 ° / ₀ of the cases the two drugs same effects elicited occurred and no observable sedative effect in 44% of cases. The carbamate was only better in 6% of all cases. The toxic effects of the two drugs are practically the same.

The acetone derivatives used as starting substances in the process according to the invention can be prepared in a manner not claimed here according to the following preliminary process
of effective as a sedative
2-phenyl- and 2-p-chloro ^ henyl-3-methyl-2,3-dihydroxy-hexene- (5)

Applicant:

L, 0vens kemiske Fabrik ved A. Kongsted, Copenhagen

Representative: Dr.-Ing. F. Wuesthoff, Dipl.-Ing. G. Pulse ,,

and Dipl.-Chem. Dr. rer. nat. E. Frhr. v. Bad luck man,

Patent Attorneys, Munich 9, Schweigerstr. 2

Claimed priority:
Great Britain 12 July 1957

Dr. rer. nat. Peter Werner Feit,

Kongens Lyngby (Denmark),

has been named as the inventor

font for the production of 2-p-chlorophenyl-acetoin.

2 g of mercury oxide are dissolved in 20 ml of 4N sulfuric acid and the solution is mixed with 30 ml of methanol. A solution of 20 g of p-chlorophenyl-methyl-äthinyl-carbinol (prepared in a known manner by reacting p-chloroacetophenone with acetylene) in 10 ml of methanol is added dropwise to the mixture at 60 to 65 ° C. in the course of I ¹ Z ₂ Hours given. The mixture is held at this temperature for 3 hours. Then 10 g of potassium carbonate are slowly added and the mixture is cooled. The resulting ketone is extracted with ether, the ethereal solution washed with water and dried over magnesium sulfate. The ether is evaporated and the residue fractionated in vacuo. 15.5 g of 2-p-chlorophenyl-acetoin, a hitherto unknown compound, with a boiling point of 147 to 148 ° C./10 mm Hg were obtained.

The 2-phenyl-acetoin can be prepared in an analogous manner will.

example 1

Preparation of 2-phenyl-3-methyl-2,3-dihydroxy-hexene (5)

2-propenyl magnesium chloride is used in a known manner from 12 g magnesium and 34.5 g 3-chloropropene in 120 ml

- 909 710/534.

Claims (15)

-3 4 produced from anhydrous ether. Given to the resulting. The mixture is then heated to 25 ° C and the suspension is stirred a solution of 16.4 g of 2-phenyl-acetoin at this temperature for 16 hours, after which it slowly into 100 ml of anhydrous ether, at 10 ⁰ C with an aqueous solution of ammonium chloride added stirring. The mixture is then set to 25 ° C. and the ethereal phase is separated off. the heated and at this temperature for 16 hours. The ethereal solution is washed with water over stirred, whereupon it was dried with an aqueous solution of ammonium magnesium sulfate and concentrated to dryness added and the ethereal phase is separated and evaporated. It becomes a partially crystalline residue will. The ethereal solution is obtained with water, which completely crystallizes with hexane. After washing again, dried over magnesium sulfate and recrystallized from hexane and benzene Evaporated dry. A partially crystalline io 2-p-chlorophenyl-3-methyl-2,3-dihydro-hexene (5) is obtained from the residue, which crystallizes completely with hexane, melting point 104.5 to 105.5 ° C,
sated. After repeated recrystallization from benzene 2-phenyl-3-methyl-2,3-dihydroxy-hexene (5) is obtained. from melting point 98 to 98.5 ° C. Process for the production of calming 15 moderately effective 2-phenyl- and 2-p-chlorophenyl- Example 2 3-methyl-2,3-dihydroxy ~ hexene- (5), thereby Production of 2-p-chlorophenyl-3-methyl- indicates that 2-phenyl- or 2-p-chlorine- 2,3-dihydroxy-hexen- (5) phenyl-acetoin with 2-propenyl-magnesium chloride . or bromide converts in a manner known per se, 2-propenyl magnesium chloride is 20 in a known manner whereupon the resulting Grignard compound in hydrolyzed from 6 g of magnesium and 17.55 g of 3-chloropropene in 60 ml in the usual way. produced from anhydrous ether. To the received - Suspension becomes a solution of 10g 2-p-chlorophenyl- Considered publications: Acetoin in 50 ml of anhydrous ether slowly at 10 ° C. German Auslegeschrift No. 1 005 952. © 909 710/534 1.60