DE1052977B - Process for the preparation of 2-AEthyl-2-sec-butyl-1,3-propane-diol dicarbamate - Google Patents

Description

kl. 12 ο 17/01

INTERNAT. KL. C 07 C

PATENT OFFICE

C 14228 IVb / 12 ο

REGISTRATION DATE: JANUARY 11, 1957

NOTICE
THE REGISTRATION
AND ISSUE OF THE
EDITORIAL: MARCH 19, 1959

The invention relates to a process for preparing a new compound, the highly effective SphI af i nd u ζ ie re nde properties. It is based on deiFTjitdeckurig, "" that in the class of 2,2-disubstituted dicarbamates a certain compound has pronounced sleep-inducing properties, namely 2-ethyl-2-sec-butyl-1,3-propanediol dicarbamate. This compound is a white crystalline solid that is soluble in most organic solvents, but has only poor solubility in water. It forms stable solutions in water and organic solvents. When heated or boiled with acid or alkali, this compound hydrolyzes to form 2-ethyl-2-sec-butyl-1,3-propanediol, ammonia and carbon dioxide.

The new compound is made by primary reaction of 2-ethyl-2-sec-butyl-1,3-propanediol with Phosgene produced with the formation of the corresponding dichlorocarbonate derivative, advantageously with addition of acid-binding agents such as sodium hydroxide, antipyrine or dialkylaniline. The dichlorocarbonate derivative is then converted into the desired by the action of anhydrous or aqueous ammonia Dicarbonate transferred.

The 2-ethyl-2-sec-butyl-1,3-propanediol used to prepare the new compound can z. B. be prepared by reducing the corresponding disubstituted malonic acid ester.

example

a) 97.7 g of diethyl ethyl sec-butylmalonate were reduced in the usual manner with 22.8 g of lithium aluminum hydride, the reduction being carried out ^{in 900 cm 3 of anhydrous ethyl ether.} The excess reducing agent was consumed by adding a small amount of ethyl acetate. The reaction mixture was treated with water and the ether-soluble fraction was removed. The solution was dried and concentrated by removing the solvent. The remaining liquid was then fractionally distilled; 54 g (84%) of liquid, which distilled the 93 to 99 ° C under 0.1 mm pressure, was specially collected. They were distilled again at 90 to 92 ° C under 0.08 mm pressure. The liquid was about 0.5% soluble in water and had a refractive index η "= 1.4625.

Analysis for C ₉ H ₂₀ O ₂ :

Calculated C 67.44, H 12.58;

found C 67.71, H 12.25.

b) In a 500-cm ⁵ flasks containing 150 cm ³ of dry, at - 10 ⁰ C chilled includes toluene, 33 g of phosgene are added (0.3 mole + 10%). Then 24 g method of manufacture

of 2-ethyl-2-sec-butyl-1,3-propane

dioldicarbamate

Applicant:

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

Representative: Dr. H.-H. Willrath, patent attorney,
Wiesbaden, Hildastr. 32

Claimed priority:
V. St. v. America January 13, 1956

Frank Milan Berger, Princeton, NJ,
and Bernard John Ludwig, North Brunswick, NJ,

(V. St. A.),
have been named as inventors

2-Ethyl-2-sec-butyl-1,3-propanediol, dissolved in 100 cm ^{3 of} toluene, with 31 g (0.3 mol) of N, N-dimethylaniline added. The internal temperature is kept at -5 to 5 ° C; the addition takes about 20 minutes. The cold reaction mixture is washed with 5% hydrochloric acid. The toluene layer is _{dried over Na 0} SO ₄ and saturated with ammonia gas, the temperature rising. The mixture is heated to reflux and filtered. The solid product, 2-ethyl-2-sec-butyl-1,3-propanediol dicarbamate, is ^{recrystallized from 150 cm 3 of} benzene. Its melting point is 119 to 120 ⁰ C.

When the compound according to the invention is applied to suitable test animals, e.g. B. Moulting, on their ability is tested to induce sleep, it turns out that it has an intense sleep-inducing effect. It it was also found that this compound was not used as an anticonvulsant to prevent its occurrence of electric shock attacks is effective because the dosage required for this purpose put all animals into a deep sleep.

Advantageously, the compound according to the invention is effective when used as an euthanasia drug no unpleasant or dangerous side effects, as are often caused by the usual used euthanasia drugs, e.g. B. the bar

809 770/485

biturate, induced. Besides, it means one Safety in use that the agent has a wide safety border between the lethal Dose and the hypnotic or drowsy doses.

The results of studies on test animals conclusively show that the compound after the Invention has unique properties in terms of its sleep-inducing effect.

The connection near the invention is first. jfc ° line is intended for oral use and is shaped into suitable pills, tablets or capsules using conventional techniques. But you can also in a suitable solvent, for. B. a mixture of water and polyethylene glycol, dissolved and used for injections or as an enema.

The substance prepared according to the invention was compared with a known, isomeric compound, namely 2-ethyl-2-n-butyl-1,3-propanediol dicarbamate, with regard to the sleep-inducing effect. The measure of this effect is the paralyzing dose (DP ₅₀ ), which, when administered interperitoneally, is a statistically determined mean that causes paralysis in the animals, which is indicated by the fact that the animals are unable to straighten themselves up again. The method is described by LC Miller and ML Tainter in Proc. Soc. Exper. Biol. And Med., 57, p. 261 [1944].

In the experiments carried out, groups of ten mice were treated in geometric progression with doses increasing by a factor of approximately 1.5. The number of animals paralyzed at each dose level was noted. In these experiments, the 2-ethyl-2-sec-butyl-1,3-propanediol dicarbamate gave a PD ₃₀ value of 315 ± 23, the 2-ethyl-2-n-butyl-1,3-propanediol dicarbamate, on the other hand, of 600 + 43. Accordingly, the sec-butyl compound according to the invention is considerably more effective than the ^ -butyl compound in terms of sleep inducing properties, since a smaller amount is required to achieve the same result.

Claims (2)

Claims. 1. \ ^ experienced in the production of 2-ethyl-2 - sec.-butyl -1,3-propanediol dicarbamate, thereby characterized in that 2-ethyl-2-sec-butyl-1,3-propanedial reacted with phosgene to form the corresponding dichlorocarbonate and this converted into the dicarbamate by the action of anhydrous or aqueous ammonia. 2. The method according to claim 1, characterized in that in the first procedural stage acid binding agent is added. Considered publications:
Journ. amer. formerly soc, 1951, p. 5780. © 809 770/485 3.