DE2552266A1 - (1)-Aryloxy or arylthio-(3)-cyclohexylamino-(2)-propanol derivs. - prepd. e.g. by reacting epoxy propane cpds. with (3,3,5)-trimethyl-cyclohexylamine - Google Patents

Abstract

New N-(2-hydroxypropyl)-cyclohexylamine derivs. are cpds. of formula (I) their salts with acceptable (in)organic acids, and their quat. cpds. with lower alkyl halides. Cpds. which a are optically active due to the asymmetric C-atom in the 2-position of the side-chain are also included. In formula (I), R is phenyl or naphthyl which may be substd. by halogen, CF3, 1-4C alkyl, 1-4C alkyl, 1-4C alkylthio, 3-6C alkenyl, NO2, amino, OH, CN, thiocyanato, 2-4C acyl, aryl, aralkyl, aralkoxy, and/or ureido; X is O or S; and R1 is H or 1-4c alkyl. (I) and their salts have valuable therapeutic properites. Specific cpds. (I) include 1-(2-chloro-5-methylphenoxy)-3-(3,3,5-trimethylcyclohexylamino)-2- -propanol. In an example, the hydrochloride of this cpd. is prepd. by refluxing 1(2-chloro-5-methylphenoxy)-2,3-epoxypropane with 3,3,5-trimethylcyclohexylamine in EtOH, removing alcohol in vacuo, dissolving the residue in Et2O, and saturating the soln. with HCl.

Description

The invention relates to new cyclohexylamine derivatives

general formula I, process for their preparation and their pharmaceutical application.

in which R denotes a phenyl or naphthyl radical, which optionally by halogens, trifluoromethyl groups, straight or branched alkyl and / or alkoxy and / or thioalkyl groups with 1 to 4 carbon atoms, alkenyl groups with 3 to 6 carbon atoms, nitro, amino, hydroxy, nitrile, rhodan, acyl with 2 am 4 carbon atoms, aryl, aralkyl, aralkyloxy groups and / or one ureido group, is optionally substituted, X for oxygen or sulfur, R1 for hydrogen or a lower alkyl group having 1 to 4 carbon atoms.

The products of the formula I according to the invention can be according to the following known processes can be obtained, where R, R1 and X in the following Formulas have the same meaning as in formula I.

1. By reacting the cyclododecylamine of the general formula II with an Arylglycidae-tller of the general formula III at elevated temperature, optionally in the presence of an inert solvent, or with a compound of the general formula IV, where lial stands for chlorine, bromine or iodine, at an elevated temperature, optionally in the presence of an inert solvent and / or an acid scavenger.

2. By reacting the 3,3,5-trimethyl-cyclohexyl-amino-2,3-oxydopropane of the general formula V or a 3,3,5-trimethyl-cyclohexyl-amino-2-hydroxy prolzan-llalogenid- (3) of the general formula VI, wherein Hal is a halogen atom, such as preferably chlorine or bromine, with a phenol or naphthol of the general formula VII at elevated temperature, optionally in the presence of an inert solvent tu1d / or in an alkaline environment.

3. By reacting a compound of the general formula VIII with a 3,3,5-trimethyl-cyclohexyl halide, preferably the chloride, at elevated temperature, optionally in the presence of an inert solvent and / or an acid scavenger, where R can be a phenol or naphthol.

4. By reducing a compound of the general formula IX to the corresponding alcohol by z. B. hydrogenation in the presence of a suitable catalyst, such as. B. platinum oxide, optionally in the equivalent of an inert solvent, where R can be a phenol or naphthol.

5. By hydrolysis of oxazolidones of the general formula X and optionally reacting the reaction product with an alkylating agent, such as. B. methyl halide, diethyl sulfate or formic acid (according to Eschweiler-Clark), optionally at elevated temperature and in the presence of an inert solvent, R can be a phenol or naphthol.

The reaction partners are largely converted into equinolar amounts Conditions.

The bases can be converted into salts with physiologically acceptable inorganic salts or organic acids.

As examples of physiologically harmless inorganic and organic Acids that are suitable for salt formation may be mentioned, hydrogen chloride, hydrogen bromide, Hydrogen iodide, sulfur, salopeter, phosphorus, vinegar, glucon, milk, malon, Malcin, amber, fumar, wine, lemon, benzoin, ß-oxynaphthol, embon or theophyllinosetic acid.

The compounds according to the invention occur according to the center of asymmetry on carbon atom 2 of the side chain in optically active isomers, which according to known Procedures can be separated.

The cyclohexylamine derivatives according to the invention and their physiological harmless salts have valuable therapeutic properties.

For example: 19.7 g of 1- (3-chloro-5-methyl-phenoxy) -2,3-epoxypropane are used with 14.1 g of 3,3,5-trimethyl-cyclohexylamine in 200 ml of abs. Ethanol approx. 8 hours heated to reflux. After the alcohol has been distilled off in vacuo, the residue becomes dissolved in ether. Hydrogen chloride is passed into this ethereal solution while cooling with ice until saturation cin. The precipitate is filtered off with suction and recrystallized from benzene.

Mp. 180-182 ° Analysis: C19H30ClNO2 x HCl mol. Wt. 376.38 calc.

C 60.63% 60.78% H 8.3% 8.33% H 3.72% 3.69% The following substances were also produced: X xe R Sum formula F (OC) ,. ,,. . C181129it02 J 1101 142 - 144 CH3 01911311102 IIC1 108 - 111 H3 9 C19II31IT02 X 1101 133 - 135 H 3C ~ 9 C19II31 Iro2 X IICl 132-133 O C2Ms 02011331103 X IICl 150 - 151 Br t c1 3II2 SrIT02 X IIG1 165 - 166 R Sum formcl 2 (OC) ct 123 0181128011 102 x 1101 123 - 125 Cle 0181128ClN02 X 1101 C 16 to I 165 NO2 - 018112811204 X 1101 166 - 167 ° 2Ng3 0 Ci 8lI28ìT2 ° 4 htl 176 - 178 CH3 t3 0201133NO2S X 1101 133 - 134

Claims (10)

Cyclohexylamine derivatives P atent claims: 1. New cyclohexylamine derivatives of the general formula I in which R denotes a phenyl or naphthyl radical, optionally substituted by halogens, trifluoromethyl groups, straight or branched alkyl and / or alkoxy and / or thioalkyl groups with 1 to 4 carbon atoms, alkenyl groups with 3 to 6 carbon atoms, nitro, amino, Hydroxyl, nitrile, raw danish, acyl with 2 to 4 carbon atoms, aryl, aralkyl, aralkyloxy groups and / or an ureide group, optionally substituted, X for oxygen or sulfur, R1 for hydrogen or a lower alkyl group with 1 to 4 Carbon atoms. 2. Process for the preparation of the compounds of the general formula I by reacting a 3,3,5-trimethyl-cyclo hexylamine of the general formula II with an aryl glycidate ether of the general formula III at elevated temperature, optionally in the presence of an inert solvent or with a compound of the general formula IV, where IIal is chlorine, bromine or iodine, at elevated temperature, optionally in the presence of an inert solvent and / or an acid scavenger, where R, R1 and X have the same meaning as in general formula I. 3. Process for the preparation of the compounds of the general formula I by reacting the 3,3,5-trimethyl-cyclohexylamino-2,3-oxydopropane of the general formula V or one,, 5-trimethyl-cyclohexylamino-2-hydroxy propene halide (3) of the general formula VI, where Hal is a halogen atom, such as preferably chlorine or bromine, with a phanol or naphthol of the general formula VII at elevated temperature, optionally in the presence of an inert solvent and / or in an alkaline Hilleu, where R, R1 and X have the same meaning as in the general formula I. 4, process for the preparation of compounds of the general formula I by reacting a compound of the general formula VIII with a 3,3,5-trimethyl-cyclohexyl halide, preferably the chloride, at elevated temperature, optionally in the presence of an inert solvent and / or an acid scavenger, where R, R1 and X correspond to the meaning of the general formula I. 5. Process for the preparation of compounds of the general formula I by reducing a compound of the general formula IX to the corresponding alcohol by z. B. hydrogenation in the presence of a suitable catalyst, such as. B. platinum oxide, optionally in the presence of an inert solvent. R, R1 and X are equal to the general formula I. 6. Process for the preparation of compounds of the general formula I by hydrolysis of oxazolidones of the general formula Jr and optionally reacting the reaction product with an alkylating agent, such as. B. methyl halide, diethyl sulfate or formic acid (according to Eschweiler-Clark) optionally at elevated temperature and in the presence of an inert solvent. R, R1 and X have the meaning given in general formula 1. 7. Salts with physiologically compatible inorganic and organic Acids. 8. Quaternary compounds with lower alkyl halides 9. OntiJch active Compounds due to the asymmetry center on carbon atom 2 of the side chain appear 10. Pharmaceutical preparations made from these compounds.