CS253446B1 - 1- (dimethylaminomethyl-cyclohexyl) -2-alkoxycarbanilate and the preparation thereof - Google Patents

Abstract

The solution relates to 1-(dimethylaminomethylcyclohexyl)-2-alkoxycarbanilates of the general formula I, where R represents 1 to 8 carbon atoms in a linear alkyl chain, a method of their preparation from 2-alkoxyphenylisocyanates of the general formula II by addition of 1-dimethylaminomethylcyclohexanol for 12 to 15 hours in a toluene environment under reflux. The final compounds are from the group of substances — carbanilates, whose salts, most often with hydrochloric acid, are characterized by local anesthetic properties.

Description

(54) 1- (dimethylaminomethyl-cyclohexyl) -2-alkoxycarbanilalates and process for their preparation

2

The present invention relates to 1- (dimethylaminomethylcyclohexyl) -2-alkoxycarbanolates of formula I wherein R is 1 to 8 carbon atoms in the linear alkyl chain, a process for their preparation from 2-alkoxyphenylisocyanates of formula II by addition of 1-dimethylaminomethylcyclohexanol for 12 to 15 hours in toluene under reflux. Finally, the compounds are from the group of carbanilate substances whose salts, most commonly with hydrochloric acid, are characterized by locally anesthetic properties.

NH-CO-O

STEED

N ^ C ~ Q

STEED

ΓΙ

The invention relates to 1- (dimethylaminomethylcyclohexyl) -2-carbanilalates of the formula I

STEED

-co -o

^CH 2 ^{N (c} ^^ 2.

(I) where

R represents 1 to 8 carbon atoms in the linear alkyl chain, a process for the preparation of these compounds. Carbanilate salts containing an amino group in their molecule are characterized by local anesthetic and, in some cases, antiarrhythmic activity. Most often, carbanilates are prepared by the addition of primary or secondary alcohols to aryl isocyanates. Addition of tertiary alcohols to arylisocyanates is difficult and the main product of this reaction is not carbanilate, but symmetrically substituted ureas.

Some simple types of such carbanilalates in which tertiary carbon is bound to the oxygen of the carbamate group have been described in the chemical literature, but the compounds of the invention are novel substances not previously described in the chemical literature. It is an advantage in the preparation of these compounds according to the invention that, by using the hitherto known method for the preparation of carbanilate by addition of primary and secondary alcohols to aryl isocyanates, carbanilate can be prepared in good yield by addition of tertiary alcohol under suitable reaction conditions. dimethylaminomethylcyclohexanol to the alkoxyphenylisocyanates of formula II

STEED

II

The compounds of the present invention are oils and cannot be purified by distillation because they decompose by heating during distillation even under reduced pressure. Another simple method of purification of these compounds has been found, which, together with the method of preparation described in Examples 1 and 2. The purification principle consists in the preparation of [1- (2) -alkoxycarbaniloyloxy) cyclohexylmethyl] dimethylammonium hydrogen oxalate from which 1- (dimethylaminomethylcyclohexyl) -2-alkoxycarbanoate is displaced by triethylamine in an aqueous medium. The examples illustrate but do not limit the use of the method for preparing the compounds of the invention and characterize their properties In addition to yields, elemental analysis results, R ₍ values (Silufol, cyclohexane: benzene: diet system) ylamine (45: 11: .3), detection under UV radiation are also given IR spectral characteristics (chloroform, v in cm ¹ ) and in some cases also ¹ H-NMR spectral characteristics (chemical shift δ in ppm).

Example 1

A mixture of 0.031 mol of 1-dimethylaminomethylcyclohexanol, 0.03 mol of 2-methoxyphenyl isocyanate and 30 cm ^{3 of} anhydrous toluene is heated under reflux for 12 hours. After cooling, 30 cm ^{3 of} hexane are added to the mixture and the precipitated solid (symmetrically substituted urea) is filtered off. The solvent and unreacted starting compounds are distilled off from the filtrate at atmospheric, ultimately under reduced pressure. The liquid residue is dissolved in 30 cm ^{3 of} anhydrous ether and a solution of 0.06 mol of anhydrous oxalic acid in 30 cm ^{3 of} anhydrous ether is added under stirring at 20 ° C. The precipitated [1- (2-methoxycarbaniloyloxy) cyclohexylmethyl] dimethylammonium hydrogen oxalate is filtered off, washed on a filter with ether and purified by crystallization from ethyl acetate. The organic layer was separated, dried over anhydrous potassium carbonate and filtered, and the solvent and excess triethylamine were distilled off to give 1- (dimethylaminomethylcyclohexyl) -2-methoxycarbanoate as a colorless oil nD ²⁰ = 1. 5306, Rf = 0.44, 36% yield;

IR spectral characteristics υ (N-Hj 3 430, v (NC-Hj 2 778), v (C = O) 1720, v (C = C) 1 605, δ (C — N — Η) 1 510;

⁴ H-NMR spectral characteristics (CH 3) 2N 2.33 CH 2 N 2.83, CONH 7.26; Analysis for C 17 H 26 N 2 O 3 (M. r. = 306.41) calculated:

% C, 66.64;% H, 8.55;% N / 9.14;

found:

H, 8.45; N, 9.02.

Example 2

To the reaction was repeated using 2-oktyloxyfenylizokyanát, workflow is identical with the procedure of Example 1 to give 1- (dimethyl mínometylcyklohexyl J oktyloxykarbanilát -2-like and colorless oil n _D ²⁰ = 1.5074, R [= 0.58, yield 52% of theory;

IR spectral characteristics v (N-H) 3 435, v (NC-H) 2 785, v (C = -O) 1725, v (C-C) 1 605, δ (C-N-Η) 1 515;

^! 1 H-NMR spectral characteristics (CH 2 N 2 2.33, CH 2 N 2.82, CONH 7.24; Analysis for C 24 H 40 N 2 O 3 (M. r = 404.60);

H, 9.97; N, 6.92. found:

% C, 73.48;% H, 10.02;% N, 6.72.

The following substances were prepared by the same procedure:

3. 1- (dimethylaminomethylcyclohexyl) -2-ethoxycarbanilate n _D ²⁰ = 1.5521;

R _f = 0.48;

yield 68% of theory;

IR: v (N-H, 3430) v (NC-H) 2 270 v (C = O) 1720, v (C-C 1 605, 5 (C-N-H) 1512;

Analysis for C 18 H 28 N 2 O 3 (M. r. = 320.44); calculated:

% C, 67.47;% H, 8.81;% N, 8.74;

H, 8.67; N, 8.38.

4. 1- (dimethylaminomethylcyclohexyl) -2-propoxycarbanilate ( _r) ²⁰ = 1.5210;

R _f = 0.51;

yield 69% of theory;

IR: v (N-H) 3430, v (NC-H) 2775, v (C = O) 1721, v (C = C) 1 605, δ (C-N-H) 1512;

Analysis for C 19 H 30 N 2 O 3 (M. r. = 334.46);

calculated:

H, 9.04; N, 8.38.

found:

% H, 9.19;% N, 8.64.

5.1- (dimethylaminomethylcyclohexyl) -2-butoxycarbainlate n _D ²⁰ = 1.5 168;

yield 76% of theory;

IR: v (N-H) 342, v (NC-H) 2780, v (C = O) 1721, v (C = C) 1 604, (C-N-H) 1 508;

Analysis for C 20 H 32 N 2 O 3 (M. r. = 348.49); calculated:

% C, 68.93;% H, 9.26;% N, 8.04; found:

% H, 9.56;% N, 8.05.

6. 1- (dimethylaminomethylcyclohexyl) -2-pentyloxycarbamate n _D ²⁰ = 1.5 1 46;

R _f = 0.54;

yield 80% of theory;

IR: v (N-H) 3430, v (NC-H) 2778, v f = O) 1720, v (C = C) 1,604, δ (N-C) H, 1511;

Analysis for C 21 H 34 N 2 O 5 (M. r. = 362.52); calculated:

% H, 9.45;% N, 7.73; found:

H, 9.38; N, 7.56.

7. 1- (dimethylaminomethylcyclohexyl) -2-hexyloxycarbanilate n _D ²⁰ = 1.5124;

Rf = 0.56;

yield 88% of theory;

IC: v (N-H) 3434, v (NC-H) 2777, v (C = O), 1720, v (C = C) 1 605, δ (C-N-H) 1513;

Analysis for C 22 H 36 N 2 O 3 (M. r. = 376.55); calculated:

% C, 70.18;% H, 9.64;% N, 7.44; found:

H, 9.22; N, 7.32.

8. 1- (dimethylaminomethylcyclohexyl) -2-heptyloxycarbanolate n _D ²⁰ = 1.5096;

Rf = 0.57;

yield 83% of theory;

IR: v (N-HJ 3 430, v (NC-HJ 2 780), v (C = O) 1 720, v (C = C) 1 605, δ (C-N-HJ 1510).

Claims (3)

SUBJECT VYNALEZU 1.1- (dimethylaminomethylcyclohexyl) -2-alkoxycarbanilalates of the formula I N’-C ~ Q (Q \ -nh-cq ~ o O ~ R π where R is a linear alkyl chain having 1 to 8 carbon atoms. 2. A process for the preparation of 1- (dimethylaminomethylcyclohexyl) -2-alkoxycarbonates of the formula I according to claim 1, characterized in that 1-dimethylaminomethylcyclohexanol is reacted with 2-alkoxyphenylisocyanates of the formula II in which: R is as defined above for 12 to 15 hours in toluene under reflux. 3. A process according to claim 2 wherein the crude 1- (dimethylaminomethylcyclohexylmethyl) -2-alkoxycarbanilate is treated with anhydrous oxalic acid to give [1- (2-alkoxycarbaniloyloxy) cyclohexylmethyl] dimethylammonium hydrogen oxalate, from which the porosine is converted into a p- of the solution displaces the 1- (dimethylaminomethylcyclohexyl) -2-alkoxycarbanilate of formula I.