DE1161254B - Process for the production of new, halogen-containing carbamic acid esters - Google Patents

Description

FEDERAL REPUBLIC OF GERMANY

GERMAN

PATENT OFFICE

EDITORIAL

Boarding school Cl .: C 07 c;

Number:
File number:
Registration date:
Display day:

C07d

German class: 12 ο -17/01

B 61399IVb / 12 ο
February 23, 1961
January 16, 1964

The invention relates to new halogen-containing carbamic acid esters the general formula

Xi - CH ₂ O Ri

X ₂ -CH ₂ -C-CH ₂ -OCN

X ₃ -CH ₂ R ₂

In this formula, Ri denotes alkyl, cycloalkyl or aryl radicals and R ₂ denotes hydrogen or alkyl radicals; Ri and R ₂ can form a heterocycle together with the amide nitrogen atom; Xi, X ₂ and X _{3 are} halogen, preferably chlorine and bromine.

These new compounds are obtained by adding pentaerythritol trihalohydrins to the general formula

Xi - CH ₂

X ₂ -CH ₂ -C -CH ₂ OH

X ₃ -CH ₂

in which X ₁ , X ₂ and X _{3 have} the meanings given above, according to methods known per se

a) with carbamic acid halides

Process for the production of new, halogen-containing carbamic acid esters

Applicant:

Aniline & Soda Factory in Baden

Aktiengesellschaft, Ludwigshafen / Rhein

Named as inventor:

Dr. August Amann,

Dr. Wolfgang Jentzsch, Ludwigshafen / Rhine,

Dr. Gerald Neubauer, Frankenthal (Palatinate)

d) with haloformic acid esters and then with an amine

Ri

Hal - C - OR ₃ + NH O

R ₂

e) with phosgene and an alcohol to a mixed carbonic acid ester and then with one Amine

Hal-C-N

OR ₂

b) with phosgene and then with an amine

Cl-C-Cl + HN

OR ₂

c) with urethanes

Ri
R ₃ OC -N

Il \

OR ₂

Cl - C - Cl + HOR ₈ + HN
0

Ri

R ₂

or
f) with isocyanates

= NR _x

Il ο

reacted, where Ri and R _{2 have} the meaning given above and R _{3 is} a lower alkyl radical.
The pentaerythritol halohydrins required for the specified process - z. B. pentaerythritol trichlorohydrin, pentaerythritol tribromohydrin or pentaerythritol dichlorobromohydrin, hereinafter referred to as hydrins for short - are obtainable in a simple and known manner from pentaerythritol.

The products of the process can, for. B. be obtained in the following way: The hydrin is dissolved in an inert solvent and sets it at elevated levels

309 779/269

Temperature, preferably in the presence of equimolar amounts of an auxiliary base, with the stoichiometric Amount of carbamic acid chloride or initially with phosgene or a chloroformic acid ester and then deal with the amine. The salts of the auxiliary base obtained in these reactions are separated off. The remaining solution is washed with water and then worked up as usual. Hydrin and phosgene can also be reacted in the presence of a lower alcohol. This gives a carbonic acid ester which, after the salts have been separated off, is moderately increased Reacts temperature with the amine. When using phosgene, it is recommended to use before Further processing, the unreacted phosgene is blown out of the solution with air or with nitrogen.

If one assumes a hydrin and a urethane in the production of the carbamic acid esters, for example, the hydrin is boiled with a five to ten fold excess of the urethane. After the reaction has ended, i. That is, when no more alcohol is split off, the reaction mixture is introduced into water and the organic one is extracted Phase with ether and work up as usual.

In the reaction with isocyanate, equimolar amounts of the hydrin and the isocyanate are allowed, ζ. B. in boiling benzene solution with the addition of catalytic amounts of a base such as sodium methylate or pyridine, react with each other. The reaction mixture that makes up the carbamic acid ester usually begins to separate out during the reaction, is worked up as usual.

The technically very advantageous process is the starting point among the manufacturing methods mentioned of hydrin, amine and phosgene, capable of the widest application.

The carbamic acid esters of pentaerythritol trihalohydrins thus obtained have excellent sedative-hypnotic properties. Compared to the carbamic acid ester known from British patent specification 850 003 of 2,2,2-tris-chloromethylethanol, the compounds according to the invention are distinguished according to previous observations by a greater therapeutic effect, d. H. through better ones Compatibility with the same effectiveness.

The parts mentioned in the examples are parts by weight.

example 1

To 58 parts of pentaerythritol trichlorohydrin, dissolved in 100 parts of dry pyridine, 33 parts of dimethylcarbamic acid chloride are added dropwise at 60.degree. The reaction mixture heats up by itself to 75 ^° C. and is subsequently stirred at this temperature for 5 hours. The excess pyridine is drawn off under reduced pressure; the remaining residue is poured into ice water and quickly extracted with ether. The ether phase is dried well and concentrated. The distillation of the remaining residue gives 48 parts (= 61%) of the Ν, Ν-dimethyl-carbamic acid - ^^^ - tris-chloromethylJ-ethyl ester in the form of a colorless oil; Boiling point 111 to 113 ° C / 0.2mm.

Example 2

40 parts of pyrrolidine-N-carboxylic acid chloride dissolved in 50 parts of dry benzene are gradually added at 40 ° C. to a solution of 58 parts of pentaerythritol trichlorohydrin, 31 parts of triethylamine and 200 parts of dry benzene. The temperature is then gradually increased and refluxed for 20 hours. After cooling, the triethylamine hydrochloride solution is filtered off with suction, the benzene solution is washed twice with 100 parts of cold water each time and the benzene is then distilled off - finally in vacuo. The remaining residue is recrystallized from alcohol or petroleum ether, 61 parts (= 71%) of N, N-pentamethylene carbamic acid (2,2,2-tris-chloromethyl) ethyl ester being obtained in the form of white crystals (melting point 74 bis 75 ^D C).

Example 3

To 64.9 parts of isopropylamine dissolved in 400 parts of dry benzene, 140 parts of ethyl chloroformate, dissolved in 100 parts of dry benzene, are added dropwise with stirring at room temperature. After 3 hours the solution is filtered, washed with water and evaporated; the residue that remains gives, recrystallized from petroleum ether, 128 parts (= 84% of theory) of N-iso-propylcarbamic acid (2,2,2-tris-chloromethyl) ethyl ester in the form of white crystals. Melting point 80 to 81 C.
The chloroformic acid ester can be obtained as follows: To 300 parts of phosgene, dissolved in 400 parts of dry toluene, 536 parts of pentaerythritol trichlorohydrin are added at -15 ° C. dissolved in 1000 parts of dry toluene, and then at -5C 518 parts of tributylamine, dissolved in 800 parts of dry toluene, were added dropwise with stirring. The cold bath is then removed, the mixture is stirred for a further 26 hours at room temperature and finally the excess phosgene is blown out with nitrogen. The reaction solution is washed twice with a mixture of ice and 2η hydrochloric acid and once with ice water, dried and concentrated. The vacuum distillation of the remaining residue gives 582 parts (= 82% of theory) of chloroformic acid (2.2,2-trischloromethyl) ethyl ester, boiling point 92 to 95 ° C./0.2 mm.

Example 4

To 396 parts of cyclohexylamine dissolved in 2000 parts of benzene, are added under stirring at 39 C. 508 parts chloroformate (2,2,2-tris-chlormethyi) -ethyl ester (s. Example 3) dissolved in 500 parts of benzene are added dropwise. After 3 hours the solution is filtered off and gently evaporated; the residue is recrystallized from benzene-petroleum ether, 530 parts (= 84% of theory) of N-cyclohexylcarbamic acid (2,2,2-tris-chloromethyl) ethyl ester being obtained in the form of white crystals. Melting point 108 to 109 ⁰ C.

Example 5

To 118 parts of isopropylamine dissolved in 2000 parts of dry benzene are added with stirring at about 35 ° C 298 parts of chloroformic acid (2,2-bis-chloromethyl-2-bromomethyl) ethyl ester, dissolved in 500 parts of dry benzene, added dropwise and worked up in the usual way. The recrystallization of the crude product from petroleum ether gives 280 parts (= 88% of theory) of N-iso-propylcarbamic acid (2,2-bis-

chloromethyl-2-bromomethyl) ethyl ester white crystals. Melting point 81 ° C.

Analysis:
Calculated
found

in shape

Cl 21.5%, Br 24.9%; Cl 22.1%, Br 24.9%.

The chloroformic acid ester can be obtained as follows: To 500 parts of phosgene, which is stored at -15 ° C has dissolved in 800 parts of dry toluene, 900 parts of pentaerythritol dichlorobromohydrin are initially added with stirring, dissolved in 2000 parts of dry toluene, and then at -5 ° C 703 parts of tri-n-butylamine, dissolved in 1,800 parts of dry toluene, added dropwise; the cold bath is then removed and the mixture is stirred another 20 hours at room temperature. The work-up is carried out as described in Example 3 Way. By distilling the crude product twice, 840 parts (= 74% of theory) pure chloroformic acid - (2,2 - bis - chloromethyl-2-bromomethyl) ethyl ester obtained; boiling point 107 ° C / 0.5 mm.

Example 6

387 parts of chloroformic acid (2,2,2-tris-bromomethyl) ethyl ester are analogous to Example 4 with 118 parts Isopropylamine implemented. The crude product is recrystallized twice from petroleum ether. You get the N-iso-propyl-carbamic acid (2,2,2-tris -bromomethyl) ethyl ester in a yield of 255 parts (= 62% of theory) in the form of white crystals. Melting point 84 to 85 ° C.

Example 7

To a solution of 96 parts of pentaerythritol trichlorohydrin and 250 parts of benzene, 1 part of soda and then 60 parts of phenyl isocyanate dissolved in 80 parts of benzene are added dropwise with stirring. The reaction mixture is then slowly heated to the boil, 1 part of sodium methylate is added after 7 hours and the mixture is refluxed for a further 4 hours. Then it is suctioned off hot and the filtrate is concentrated by half. The N-phenylcarbamic acid (2,2,2-tris-chloromethyl) ethyl ester which precipitates as a crude product on cooling is recrystallized from benzene. Yield 151 parts (= 97% of theory). Melting point 106 to 108 ⁰ C.

Claims (1)

Claim: Process for the preparation of new, halogen-containing carbamic acid esters of the general formula XiCH ₂ O \ Il X ₂ CH ₂ -C - CH ₂ O - C X ₃ CH ₂ ■ N Ri R ₂ 50 55 60 in which Ri is alkyl, cycloalkyl or aryl radicals and R2 is hydrogen or alkyl radicals, where Ri and R ₂ can form a heterocycle together with the amide nitrogen, and in which Xi, X ₂ and X3 are halogen, preferably chlorine or bromine, characterized in that , that one pentaerythritol trihalohydrins of the general formula Xi - CH ₂ X ₂ -CH ₂ -C -CH ₂ OH X3 - CH ₂ in which Xi, X ₂ and X3 have the meaning given, in a manner known per se a) with carbamic acid halides Ri Shark - C - N OR ₂ or b) with phosgene and then with an amine Ri Cl - C - Cl + HN Il \ OR ₂ or
c) with urethanes Ri R ₃ O-C-N Il \ OR ₂ or d) with haloformic acid esters and then with an amine Ri Hai - C - OR ₃ + NH Il \ OR ₂ or e) with phosgene and an alcohol to a mixed carbonic acid ester and then with an amine Ri Cl - C - Cl + HOR3 + HN OR ₂ or f) with isocyanates C = N-Ri reacted, where Ri and R _{2 have} the meaning given above and R3 is a lower alkyl radical. Documents considered: German Patent No. 95,375; German interpretative document No. 1 037 443; British Patent No. 850 003. A test report was displayed when the registration was announced. 309 779/269 .1.64 © Bundesdruckerei Berlin