DE1179924B - Process for the preparation of carbamic acid esters of alkyl benzyl carbinols - Google Patents

Description

FEDERAL REPUBLIC OF GERMANY

Boarding school Cl .:

C 07 c

GERMAN

PATENT OFFICE

EDITORIAL

German class:

Number:
File number:
Registration date:
Display day:

12 ο -17/01

S 64203 IVb / 12 ο
July 30, 1959
October 22, 1964

The invention relates to a process for the preparation of carbamic acid esters of alkylbenzyl carbinols by known conversion of carbinols of the general formula

5 rows

CH ₂ -CH-OH

in which R is a saturated or unsaturated, straight or branched alkyl group and the Phenyl nucleus can carry an alkyl, aryl, aralkyl group, a halogen or an alkoxy group with

a) Phosgene in the presence of a tertiary base and subsequent reaction of the obtained Chloroformic acid ester with ammonia,

b) urea chloride,

c) urea or its salts or

d) ethyl carbamate.

The products of the process according to the invention represent pharmacologically valuable compounds This is what causes higher doses of the carbamic acid ester of isopropyl-benzyl-carbinol in mice Excitement. The other carbamic acid esters described below have very high low toxicity analgesic, antipyretic, anti-inflammatory, sedative and strong anticonvulsant Effect. When administered in the appropriate dose, they prevent the occurrence of electric shock as well as pentamethylenetetrazole and strychnine convulsions. Your superiority over comparable known drugs can be detected using the slide test with mice, in which the well-known phenyl isopropyl methyl carbamate shows practically no effect, while the carbamic acid ester obtainable according to the invention of Methyl-benzyl-carbinol is effective for about 4 hours under otherwise identical test conditions. After this time, the effectiveness decreases only slowly.

Some of the products of the process are distinguished by the fact that their pharmacological effect is very clearly evident even when administered orally.

In the production of the process products from the corresponding, some not yet described Alcohols, a catalyst can optionally be used. The carbamic acid esters obtained represent crystalline substances, most of which are only sparingly soluble in water.

Process for the preparation of carbamic acid esters of alkyl-benzyl-carbinols

Applicant:

Siegfried Aktiengesellschaft, Zofingen (Switzerland)

Representative:

Dipl.-Chem. Dr. jur. W. Beil and A. Hoeppener,

Lawyers,

Frankfurt / M.- Höchst, Antoniterstr. 36

Named as inventor:

Dr. Hans Saner, Oberbuchsiten,

Dr. Theodor Wagner-Jauregg, Zofingen

(Switzerland)

For the production of the not yet described alkylbenzyl-carbinols, which serve as starting materials, no protection is sought.

The following examples explain the process according to the invention.

example 1

14 g of methyl-benzyl-carbinol are dissolved in 100 ml of ether and left to stand overnight with 10 g of urea chloride. The ether is driven off, the residue is washed with warm water, dried and recrystallized from petroleum ether. The carbamic acid ester of methyl-benzyl-carbinol melts at 65 to 67 ° C.
Analysis:

Calculated

found

7.77% N;
7.88% N.

Example 2

To 55 ml of 19% strength solution of phosgene in toluene are added dropwise at 10 to 15 ° C with stirring, a mixture of 13.6 g of methyl-benzyl-carbinol (obtainable by reduction of the corresponding ketone with Raney nickel at 6O ⁰ C and a pressure of 90 atmospheres or by reacting phenylmagnesium bromide with propylene oxide according to Journ. Am. Chem. Soc, 62 [1940], p. 2295) and 12.1 g of N, N-dimethylaniline, stirred for 6 hours at room temperature and left to stand overnight. The next day, about 1 part by volume of ice water is stirred and the

409 708/420

separated organic phase. About 70 ml of 25% strength ammonia are then added dropwise at 0 to 10 ^° C. with stirring, and the mixture is stirred for ¹ 1/2 hour without cooling. The toluene phase is then separated off, dried and the toluene is completely evaporated off in vacuo on a boiling water bath. The residue solidifies in crystalline form and is filtered off after trituration with petroleum ether. 16.8 g (93%) of carbamic acid ester of methylbenzylcarbinol are obtained in the form of a colorless powder; F. = 67 ⁰ C.

Example 3

Ethyl benzyl carbinol, obtained by reducing ethyl benzyl ketone with z. B. LiAlHU (bp = 107 ³ C / 13 mm; nf = 1.5167) is converted into the carbamic acid ester according to the procedure of Example 1 or in the following way:

To 150 g of a 20% solution of phosgene in toluene at 0 to 5 ° C, a mixture of 30 g of ethyl-benzyl-carbinol and 30 g of dimethylaniline in 300 ml of toluene were added dropwise. The mixture is stirred overnight, and the precipitated dimethylaniline hydrochloride is filtered off and stir the toluene solution into 300 g of 25% NH3 with good cooling. The failed one Carbamic acid ester is suction filtered, washed and extracted from dilute alcohol or from Recrystallized petroleum ether. Yield: 28 g; F. = 61 to 62 C.

Analysis:
Calculated
found

7.25% N;
7.35% N.

Example 4

n-Propyl-benzyl-carbinol, obtained from 15 g of Mg turnings, 65 g of benzyl chloride and 36 g of n-butyraldehyde (b.p. = 120 to 122 ° C / 13 mm; nl ° = 1.5100), is according to the method of Example 3 or converted into the corresponding carbamic acid ester by reaction with urea at elevated temperature. F. = 64 to 65.5 ° C.
Analysis:

Calculated

found

6.76% N;
6.90% N.

Example 5

45

Isopropyl-benzyl-carbinol, obtained from benzylmagnesium chloride and isobutyraldehyde (bp = 116 to 118 ° C / 12mm; n ² g = 1.5080), is converted into the corresponding urethane by the process of Example 3 or by reaction with ethyl carbamate. F. = 67 to 68 ⁰ C.
Analysis:

Calculated ... 6.76% N; found ... 6.77% N.

Example 6

To produce the starting material, methylp-chlorobenzyl-carbinol, a Grignard solution is made from 18 g of magnesium turnings, 114 g of p-chlorobenzyl chloride and 420 ml of ether, and 45 ecm of acetaldehyde is added to this solution, cooled to -15 ° C., from an ice-cooled dropping funnel added dropwise to 150 ml of ether, the reaction temperature being kept between 3 and 7 ° C. Customary work-up gives 47 g of the carbinol. Bp = 125 ° C / about 2mm; nf = 1.5394; £> ³⁰ = 1.12.

The carbinol thus obtained is left dissolved in 10 parts of ether with a 10% excess Stand on urea chloride for 3 days, wash the ethereal solution with water, dry, evaporate and crystallize the residue with the addition of activated charcoal twice from petroleum ether-benzene. You get small colorless crystals; F. = 95 to 97 ° C (corrected). Yield: one third of the amount by weight of that used Carbinols.

Example 7

_{30 g of carbamic acid chloride (NH 2} COCl) are added to 58 g of o-chlorobenzyl-methyl-carbinol with a boiling point of 122 to 123 C / 13 mm (made from o-chlorobenzyl magnesium chloride and acetaldehyde in 580 ml of ether) and the mixture is left to stand for 2 days . After recrystallization from cyclohexane and then from benzene-petroleum ether, work-up gives the carbamic acid ester which crystallizes in fine needles. F. = 104 to 107.5 C.

Analysis:

³⁰ Calculated Found 16.62% Cl;
16.63% CI.

Claims (1)

Claim: Process for the preparation of carbamic acid esters of alkyl-benzyl-carbinols, characterized in that in in a manner known per se, carbinols of the general formula CH ₂ -CH-OH in which R is a saturated or unsaturated, straight or branched alkyl group and the phenyl nucleus is an alkyl, aryl, aralkyl group, a halogen or an alkoxy group can wear, either a) with phosgene in the presence of a tertiary base and then the resulting Can chloroformic acid ester react with ammonia or b) reacts with urea chloride or c) reacts with urea or its salts or d) allowed to react with carbamic acid ethyl ester. Documents considered: German Auslegeschrift No. 1020 017. 409 708/42 «10.64 © Bundesdruckerei Berlin