DE1041490B - Process for the preparation of 2-methyl-2-sec-butyl-1,3-propanediol dicarbaminate - Google Patents

Description

The present invention relates to a process for the preparation of a novel compound having a strong sleep effect. Compared with other 2,2-disubstituted dicarbaminates, that which can be prepared according to the invention possesses 2-methyl-2-sec-butyl-1,3-propanediol dicarbarninate has a remarkably good sleep effect.

The new compound is a white crystalline solid that resides in most organic solvents is soluble, but only slightly dissolves in water. It forms with water and organic solvents constant solutions. When heated or boiled with acid or alkali it will form the corresponding 2,2-disubstituted 1,3-propanediol, ammonia and carbon dioxide hydrolyzed.

The new compound is made by adding 2-methyl-2-sec-butyl-l, 3-propanediol with phosgene to the converts corresponding dichlorocarbonate. This reaction is caused by the addition of acid-binding agents, such as Sodium hydroxide, antipyrine, dialkylaniline, and the like, are favored among the reactants. The dichlorocarbonate is then treated with ammonia, using either anhydrous or aqueous ammonia used, converted to dicarbaminate.

The compound can also be obtained by transesterification of a low molecular weight urethane with the disubstituted one Propanediol are produced. The 2-methyl-2-sec-butyl-1,3-propanediol used to make the new dicarbamate can be in any known manner, e.g. B., as described below, by reducing the corresponding disubstituted malonic ester.

92 g of diethyl sec-butyl methylmalonate were reduced in the usual manner using 22.8 g of lithium aluminum hydride in a suitable volume of anhydrous ethyl ether. The resulting mixture was then treated with 10 ° / ₀ sulfuric acid and extract the ether-soluble constituents. The ether solution was dried using a suitable drying agent and the residue obtained after removal of the ether was purified by distillation under reduced pressure. The material obtained was further purified by another distillation. About 46 g of 2-methyl-2-sec-butyl-1,3-propanediol were obtained in the form of a clear, colorless liquid, the boiling point of which was 92 to 97 ° C. (0.1 mm pressure); Refractive index n% = 1.4587. The solubility in water was about 0.5%.

Analysis for C ₈ H ₁₈ O ₂ :

Calculated C 65.7%, H 12.4%;
found C 66.1%, H 12.1%.

The following example illustrates the preparation of 2-methyl-2-sec-butyl-1,3-propanediol dicarbaminate Transesterification of a urethane.

Process for the preparation of 2-methyl-2-sec-butyl-1 _r 3-propanediol dicarbaminate

Applicant:

Carter Products, Inc.,
New York, NY (V. St. A.)

Representative: Dr. W. Beil, lawyer,
Frankfurt / M.-Höchst, Antoniterstr. 36

Claimed priority:
V. St. v. America November 29, 1955

Frank Milan Berger, Princeton, N. J.,

and Bernard J. Ludwig, Middlesex, N. J. (V. St. Α.),

have been named as inventors

example 1

14.6 g of 2-methyl-2-sec-butyl-1,3-propanediol and 18.7 g of ethyl urethane are dissolved in about 100 ecm of anhydrous toluene. 3 g of aluminum isopropoxide are added and the mixture is distilled to remove the ethyl alcohol formed by the reaction of the ethyl urethane with the diol. The alcohol distills off in the form of an azeotropic mixture with toluene. The distillation is continued until the theoretical amount of ethanol has been removed.

The toluene is distilled off from the mixture under reduced pressure. The residue is dissolved in hot, aqueous isopropanol. The hot solution is filtered and allowed to cool, whereupon about 14 g of product separate out. The purified product is obtained in a yield of about 60% of theory and melts at 77 to 79 ^° C. The solubility in water is about 0.1%.

Analysis for C ₁₀ H ₂₂ O ₁ N ₂ :

Calculated N 12.06%;

found N 12.02%.

Example 2

In a 500 ecm flask, the 150 ecm Contains dry toluene cooled to -10 ° C., 33 g of phosgene (0.3 mol I-10%) are added. The received The mixture is 21.9 g (0.15 mol) of 2-methyl-2-sec-butyl-1,3-propanediol added that in 100 ecm 31.3 g (0.3 mol)

80i 659/421

Ν, Ν-dimethylaniline containing toluene is dissolved. The temperature of the contents of the flask is kept at -5 to -5 ¹ C. The addition takes about 20 minutes. Then removed the ice bath, the reaction mixture is allowed to warm to room temperature and stirred · 3 ¹ O hours. It is then cooled to 0 ⁰ C, and extracted with 150 cc S '/ cent hydrochloric acid. The toluene layer is dried over sodium sulfate and saturated with gaseous ammonia, the temperature rising to 40 ° C. The mixture is then heated to reflux and nitrated. After the filtrate has cooled, the solid 2-methyl-2-sec-butyl-1,3-propanediol dicarbamate is collected and recrystallized from 150 ecm benzene. The yield is 20 g (60% of theory). Melting point: 75 to 78 ° C.

The connection that can be produced according to the invention causes in experimental animals, such as mice, a strong drowsy effect. Such an effect is achieved with the isomeric 2-methyl-2-n-butyl-1,3-propanediol dicarbaminate surprisingly not observed.

In addition, 2-methyl-2-sec-butyl-1,3-propanediol dicarbaminate has an effect counteract the convulsions caused by electric shock, as the following test results show using known Sleep pills were used as comparison substances.

Against electric shock
protective middle
intraperitoneal
dose mg / kg 2-methyl-2-sec-butyH, 3-propane
diol dicarbaminate 170 ± 15 2-methyl-2-isopropyl-1,3-propane
diol dicarbaminate 500 ± 23 3-JI ethyl-1-pentm-3-olcarbaminate .. > 940

The compound that can be produced according to the invention does not lead to unpleasant effects when used as a sleeping aid or dangerous side effects that often occur with the usual sleeping pills, e.g. B. the barbituric acid preparations, appear. In addition, their use is completely safe, since it is between the fatal and the soporific effective dose is a "standard safety range".

The 2-methyl-2-sec. - butyl -1,3 - propanediol dicarbaminate primarily intended for oral use and is made into pills, tablets according to known methods or capsules processed. It can also be done with a suitable solvent, such as a mixture of water and polyethylene glycol, are transferred to a solution suitable for injection or use as an enema will.

Claims (2)

Patent claims: 1. Process for the preparation of 2-methyl-2-sec-butyl-1,3-propanediol dicarbaminate, characterized in that 2-methyl-2-sec-butyl-1,3-propanediol a) with a low molecular weight urethane or b) the diol is reacted with phosgene and the dichlorocarbonate obtained is converted into the dicarbaminate with ammonia converts. 2. The method according to claim 1, characterized in that that the reaction of the dichlorocarbonate in the presence of an acid-binding agent, such as sodium hydroxide. 35 Publications considered:
Austrian patent specifications No. 180 566, 180 063; Journ. amer. formerly soc, 1951, p. 5780. © 809 659/421 10.