DE838002C - Process for the production of phenolic ethers - Google Patents

Description

Issued on the basis of the First Transitional Act of July 8 , 1949

(WiGBL p. 175)

FEDERAL REPUBLIC OF GERMANY

ISSUED MAY 5, 1952

GERMAN PATENT OFFICE

PATENT LETTERING

CLASS 12q GROUP 14o4

C. 809 IV c j 12q

Dr. Hans Suter, Dörflingen, Schaffhausen, and

Werner Kündig, Schaffhausen (Switzerland)

have been named as inventors

Cilag Aktiengesellschaft, Schaffhausen (Switzerland)

Process for the production of phenolic ethers

Patented in the territory of the Federal Republic of Germany on April 14, 1950 Patent application published October 26, 1950

Grant of patent announced on March 27, 1952 The priority of the application in Switzerland of May 13, 194β has been claimed

The invention relates to a process for the preparation of therapeutically valuable compounds the general formula

--0 ("H ₂ - (CH) _n -CH ₂ OH
OH

R.

in which R ₁ . R, and R _{3 are} lower alkyl radicals and η are the numbers ι to 4 l> edeut.

ICs have been found that the phenolic ethers of this formula affect the nervous system by

they ζ. Usually cause the muscles to relax.

The new compounds should find pharmaceutical use, but should also be used as an intermediate ao products are used to manufacture potent pharmaceuticals.

The process for the preparation of the new phenol ethers is characterized in that one Compound of the general formula »5

R ₂ - <

OH

in which R ₁ , R ₂ and R _{3 are} lower alkyl radicals, with a compound of the formula

X-CH ₂ - (CH) _n -CH ₂ OH

in which X is a group capable of introducing the remainder connected to it, such as B. the hydroxyl group, halogen, one with an inorganic acid such. B. sulfuric acid or phosphoric acid, esterified hydroxyl group or a hydroxyl group esterified with an organic sulfonic acid, means and η can be the numbers ι to 4, is implemented.

You can z. B. a phenol corresponding to the general formula with a polyoxy compound Heat in a stream of hydrogen until the required amount of water has been split off. Another Variation of the method for the preparation of the new phenol ethers consists in the fact that one of the general Formula corresponding phenol with a halohydrin, e.g. B. with a glycerin-a-halogenhvdrin, in the presence of a hydrogen halide agent.

The new ethers can also be obtained by reacting a phenol with a tosyl or mesyl ester a polyoxy compound, e.g. B. with glycerine atosyl or glycerol-a-mesyl ester will. In this method, too, an acid-binding agent is expediently added.

example 1

14 g mesitol (2,4,6-trimethylphenol) are mixed with 30 g glycerol and 15 g of anhydrous N ^T atriumacetat to "triturated intimate slurry and heated in a hydrogen stream 16 hours 210 to 220 ^0th After cooling, which becomes a resinous The solidified reaction mixture was taken up in water and the solution made strongly alkaline with sodium hydroxide solution. It is then extracted several times with chloroform, the chloroform extract is washed with water, dried over sodium sulfate and then evaporated to dryness.

The residue is distilled in a high vacuum. The 2, 4, 6-trimethylphenyl (2 ', 3'-dioxypropyl) ether formed passes over at 144 to 147 ^{0 under a pressure of 0.004 mm} Hg. It forms colorless needles that melt ^{at 60 to 62 0.} The new ether is easily soluble in ethanol, methanol, acetone and chloroform. It is sparingly soluble in water and petroleum ether.

Example 2

4/6 R 2. 4, 6-trimethylphenol (mesitol) are added to a solution of 88.5 g of sodium in 1440 ecm of absolute ethanol. The whole is heated to the boil and 464 g of glycerol-a-monochlorohydrin are added dropwise with stirring over 30 minutes. The reaction mixture slowly begins to turn yellow and sodium chloride separates out. The mixture is boiled for an hour, stirring continuously, and then allowed to cool. The table salt is sucked off and washed out three times with 100 ecm of ethanol each time. The combined ethanolic filtrates are evaporated and the residue is distilled in a high vacuum. After the glycerol monochlorohydrin has been separated off, about 50 g of mesitol can be recovered as first runnings. About 500 g of 2, 4, 6-trimethylphenyl (2 ', 3'-dioxypropyl) ether below 0.004 mm Hg at 144 to 147 ⁰ distill over as the main fraction. The yield is 68% of theory.

In a manner similar to that described in the examples, the following can be prepared:

From 2,4,6-triethylphenol and a glycerine-α-halohydrin of 2,4,6-triärhylphenyl (2 ', 3'-dioxypropyl) ether a colorless oil with a b.p. 161 to 163 ⁰ under 0.003 ^mm Hg, easily soluble in organic solvents, very sparingly soluble in water.

From 2, 4, 6-tri-n-propylphenol and a glycerol-ct-halohydrin of 2, 4, 6-tri-n-propylphenyl- (2 ', 3'-dioxypropyl) -ether a colorless oil with bp. 175 to 178 ⁰ below 0.005 mm Hg, slightly soluble in organic solvents, very slightly soluble in water.

Claims (3)

Patent claims: i. Process for the preparation of phenol ethers, characterized in that one Compound of the general formula > —OH R, in which R ₁ , R ₂ and R _{3 represent} lower Al1 <yl radicals l> e, with a compound of the formula X-CH ₂ - (CH) _n -CH ₂ OH OH in which X is a group capable of introducing the radical connected to it and η denotes the numbers 1 to 4. 2. The method according to claim 1, characterized in that that one with a compound of the formula X-CH ₂ - (CH) _n -CH ₂ OH OH in which X is the hydroxyl group and η is the number ι, implements. 3. The method according to claim 1, characterized in that that one with a compound of the formula X-CH ₂ - (CH) ₁₁ -CH ₂ OH OH in which X is halogen and η is the number 1, converts and the reaction with the aid a hydrogen halide binding agent performs. Referred publications: Chemical Abstracts. Vol. 41, p. 5969 (1947); Vol.43. S-311 and 312 (1949); B e i 1 s t e i η, 4th ed., Vol. 6, pp. 149 and 354, supplementary work, Vol. 6, pp. 85 and 86; Houben, The Methods of Organic Chemistry, 3rd Vol., Pp. 107, 121, 122; German Patent No. 282991; Nature 159, pp. 813 and 814 (1947). 5137 4.52