PL96532B1 - THE METHOD OF MAKING NEW BENZYLOAMINES - Google Patents

Description

The subject of the invention is a method of producing new ones benzylamines of general formula I wherein R x is hydrogen or aliphatic or optionally substituted an aromatic acyl group, R2 is a hydrogen atom, chlorine or bromine, R3 is fluoro, methyl 5 at the 3, 4 or 5 position or when Rt is aliphatic or an optionally substituted aromatic acyl group or when R2 is chlorine or bromine also in position 2 or 6 phenyl ring, straight or branched an alkyl group of 2 to 4 carbon atoms, a trifluoro group methyl, cyano, carbamyl, carboalkoxy, ace- back, or 1-hydroxyethyl, carboxyl group when at least one of the symbols R ± and R2, R4, or R5 is not hydrogen, an alkoxy group in the 3, 4 or 5 position, or when R2 is chlorine or bromine also in the 2 or 6 position of the phenyl ring or the aminomethyl group of the formula 3, wherein R6 and R7 are the same or different and represent an alkyl, cycloalkyl or hydroxycycloalkyl group or together with the nitrogen atom form a pyrrolidine ring, piperidine or morpholine, R4 and R5 are the same or 20 different and denote hydrogen atoms, straight or branched an alkyl group of 1-5 carbon atoms, or optionally lower than substituted with 1 or 2 hydroxyl groups, alkenes- Io having 2 to 4 carbon atoms, optionally substituted by 1 or With 2 hydroxyl groups a cycloalkyl group with 5-7 25 carbon atoms, benzyl, morpholinocarbonyl- methyl or together with the nitrogen atom form the ring pyrrolidine, piperidine, hexamethylene amine, mor folinic, N-methylpiperazine or camphidine.

The novelty of the compounds obtained by the method of 30 The invention results primarily from its use as starting products of formula 2 of the new compounds, nowhere undefined.

The most closely related of the known compounds is 2-amino- -N-cyclohexyl-3,5-dibromo-N-methyl-benzylamine (Bromhexine). It demonstrates in conducted research on guinea pigs secretion increase by 46% and the answer the corresponding nitro compound only 25%. From the following the data shows that the compounds obtained the way according to of the present invention have at least twice the activity secretolytic spanking.

The compounds of the general formula I and their physiological properties soluble salts with inorganic or organic acids mi exhibit valuable pharmacological properties in particular, anti-ulcer, secretolytic action antitussive and increasing effect on production surfactant or anti-hypothermia lung follicles.

According to the invention, new compounds are produced by reductions of a compound of formula II wherein R2 - R5 have the meaning given above.

The reductions are carried out effectively in a solvent, such as water, methanol, ethanol, water / methanol, or acetate of ethyl, especially with the aid of hydrogen in statu nascendi, e.g. * using zinc / glacial acetic acid or iron / / hydrochloric acid> with hydrogen in the presence of a catalyst like nickel Raney, platinum or palladium / carbon, by means of a complex a metal hydride such as lithium aluminum hydride or tin chloride (II) hydrochloric acid, effective at temperature 0-100 ° C. vol yS 96 532 \ ^ ¦., V :: -: '* ¦¦¦¦ <' ^ f ¦ ¦: For the preparation of the compound of general formula I where R3 represents an acetyl group and / or R * and / or R5 represents a group alkenyl, reactions are carried out especially with tin chloride / / II / and / hydrochloric acid.

If the reductions are carried out catalytically activated with hydrogen in the presence of the corresponding acid anhydride carboxylic acid, the compound of formula is then obtained general 1, wherein R x is the corresponding acyl group.

If a compound of the general formula I is obtained, in which rhyme R3 is nitrile, then it can be as by partial hydrolysis, e.g. by means of a water-alcohol reflux the sodium liquor solution to the a suitable carbamyl compound of general formula I and / or a compound of formula I, wherein Rt is an atom hydrogen and R2, R3, R4 and R5, except for the containing group reactive hydrogen atom as defined above, this compound can then be acylated. He leads these reactions effectively with the aid of a reactive derivative acid, such as acid halide, acid anhydride owls or mixed acid anhydride or in the presence of a water repellant such as N, N'-bi-cycle hexyl carbodiimide.

The compounds of general formula I obtained can optionally be used do not carry out with inorganic or organic acids into their physiologically acceptable addition salts with 1,2 or 3 equivalents of the appropriate acid. Respond with suitable acids are, e.g. hydrochloric acid, hydrobromic acid, sulfuric, phosphoric, lactic, lemon, tartaric, decreasing new, or fumar.

Used as starting products compounds with formula general 2 is prepared by known methods, e.g. reaction of the corresponding benzyl halide with the appropriate amine.

As already mentioned above, the new compounds of the general formula nym 1 have valuable pharmacological properties, especially they show anti-ulcer activity, secretory tolytic, antitussive and potentiating effect generation of an agent acting on the surface or follicular anti-nephropathy factor.

They were tested for biological activity new relationships, the following example title substances: A == 2-amino-3-bromo-5-carboethoxy hydrochloride N, N-diethylbenzylamine, B = N-ethyl-2-amino-3-bromo-5-carbohydrate hydrochloride ethoxy-N-cyclohexylbenzylamine, C = N-ethyl-2-arnino-5-bromo-N-cyclo hydrochloride hexyl-3-fluorobenzylamine, D = N- (2-amino-5-bromo-3-methyl- dihydrochloride lobenzyl / hexamethyleneamine J, E = N- (2-amino-5-bromo-4-III- dihydrochloride -before butylbenzyl) -morpholine, F = 5-acetyl-2-amino-3-bromo-N, N-dimethylbenzy- lamina and G = 2-arnino-3-bromo-N, N-dimethyl, hydrochloride -5-fluorobenzylamine. 1. Secretolytic activity. Coughing up attempts was carried out on narcotic sleepy guinea pigs or rabbits (Perry and Boyd, Pharmacol. exp. Therap. 73, 65 (1941)). The substances were applied from 6 to 8 each time to experimental animals at a dose of 8 mg / kg orally.

Calculation of the secretion boost (value over 2 hours) was done by comparing the amount of discharge after and prior to test substance administration.

The circulation test was carried out on 3 cats each time 532 and '' 4 in an anesthetic state of chloralose-urethane after intravenous administration the dose of the test substance in each case in the amount of 2.4 and 8 mg / kg.

The results of the tests on guinea pigs are summarized in the following block 1.

Table 1 Substance AND B C. D Increase secretion + 90% + 81% + 100% + 84% Action on the circulatory system new 2.4 and 8 mg / kg: no change 2.4 and 8 mg / kg: no change The results of the rabbit studies are summarized in Table 2.

Table 2 Substance D E. F. Increased secretion + 72% + 77% + 75% 2. Anti-ulcer action. Activity of the respondents ulcerative substances was determined by the K. Takagi method and others. (Jap. J. Pharmac. 19, 418 (1969)). For this purpose alone micome of rats with a body weight of 220-250 g in a state of of the ether goat, the abdominal cavity was opened and removed stomach. Then in the space between the muscularis muscosae and 0.05 ml of a 5% solution was injected under the gastric mucosa acetic acid. After injection, the abdominal cavity closed back. Ulcers appearing after 3–5 days on the mucosa at the site of the acid injection heals in 3 weeks thanks to doping of the test substance in doses of 50-100 mg / kg to the feed (6 animals / dose). The control animals received only powdered food. After 3 weeks of treatment Forty animals were sacrificed, their stomachs removed and determined ulceration measure the length and width of the ulcer. Action substances were determined by comparing them with the results obtained in control animals (100%), At a dosage of substance A of 50 mg / kg orally 45, the ulcer was reduced by 52%, and at at 100 mg / kg orally there was a reduction ulcers by 79% from control animals. 3. Acute Toxicity. Acute study toxicity substances were roughly determined on groups of white mice 50 years after a single dose of 1000 or 2000 mg / kg orally. The results are given in Table 3.

Table 3 Substance AND B ¦ C D ¦ E.

Acute Toxicity > 2000 mg / kg orally (none of the 5 animals the order did not fall) > 1000 mg / kg orally (none of 5 animals the order did not fall) > 1000 mg / kg (none of the 5 animals padlo) > 1000 mg / kg orally (none of 5 animals the order did not fall) 1 > 1000 mg / kg orally (none of 5 animals the government did not fall) | 96 532 Substance F. G. Acute toxicity | > 1000 mg / kg orally (2 animals from the po Wednesday 5 padly) > 1000 mg / kg orally (none of 5 animals the order did not fall) The new compounds of general formula 1 are applicable of pharmaceuticals in the form of known preparations pharmaceutical installments, such as tablets, dragees, capsules, suppositories, ampoules and solutions, optionally in fields mixing with other active substances. Unit doses they are, in particular, 1-100 mg, in particular 4-60 mg, and the doses the daily amount is 2-300 mg, especially 4-200 mg.

In the case of compounds with a secretolytic activity unit dose is 1-20 mg, especially 4-15 mg, and in the case of anti-ulcer activity, this dose "is 25-100 mg, especially 35-60 mg.

The following examples explain the invention in more detail, no limiting its scope Example I. 2-Amino-3-bromo-5-carboethoxy-N, N- - dimethyl benzylamine. - 2 g 3-bromo-5-carboethoxy-N, N-diethyl-2-nitro-ben- nylamine is dissolved in 20 ml of ethanol and upon addition 0.2 g of Raney nickel is hydrogenated at room temperature, under 5 atm of hydrogen. The catalyst drains away, the solution is concentrated to dryness in a vacuum and the residue is cleaned by silica gel chromatography (euent: chloroform: ethyl acetate = 6: 1) and basically performed into the hydrochloride, mp: 165-168 ° C.

Example II. 2-amino-3-bromo-5-carbamyl-N, N- - dietikfcbenzylamine. 2-amino-3-bromo-5-cyano-N, N-diethylbenzyl- The amines are boiled under reflux with 70 ml ethanol and 100 ml of 5N sodium liquor. After cooling, the dilution It is quenched with 100 ml of water and extracted with chloroform. Extract chloroform is dried over sodium sulfate, concentrated and the residue recrystallizes from isopropanol. Receives sie 2-amino-3-bromo-5-carbamyl-N, N-diethylbenzyl- amine, mp: 140-142 ° C.

Example III. 2-acetylamino-3-bromo-5-carboeto- xy-N, N-diethylbenzylamine. 1 g 2-amino-3-bromo-5-carboethoxy-N, N-diethyl-ben- The zylamine is dissolved in 2 ml of acetyl chloride and heated for 1 hour to 50 ° C. Acetyl chloride dec it evaporates in a vacuum, the remainder is treated with a cold solution with thinned ammonia and chloroform, chlorine solution the mold is evaporated and the residue is cleaned as a half power of silica gel chromatography (euent: ethyl acetate), the residue after evaporation of the eluate dissolves in isopropanol and by adding isopropanol solution of hydrochloric acid and ether, leads to crystallization 2-acetylamino-3-bromo-5-carboethoxy-N, N chlorohydride -diethylbenzylamine. Melting point: 190— —194 ° C.

Example IV. 2-acetylamino-3-bromo-N, N-two- ethyl-5-methylbenzylamine. 1.53 g of 2-amino-3-bromo-N, N-diethyl hydrochloride -5-methylbenzyl amine is dissolved in 50 ml of anhydride acetic acid at 75 ° C. It evaporates in a vacuum to dryness and the residue recrystallizes from ethanol. Received many 2-acetyl hydrochloride> aniino-3-brorno-N, N-two- ethyl-5-methylbenzylamine melts in temperature 170-172 ° C. 6 Example V. 2-acelylamino-3-bromo-N, 5-dimene- tyl-N- (trans-4-hydroxycyclohexyl) benzylamine. 2.2 g 2-amino-3-bromo-N, 5-dimethyl-N- (trans-4-hy- Droxycyclohexyl) benzylamine is dissolved in 100 ml methanol and heated to boiling. Within 2 hours he adds 75 ml of acetic acid anhydride, distilled off the resulting acetic acid methyl ester is caught.

It is evaporated in a vacuum and re-evaporated after a day giving more methanol. The resulting residue was and dissolved in ethanol and converted into ethanolic solution rem hydrochloric acid into 2-acetylamino-3- hydrochloride -bromo-N, 5-dimethyl-N4 (trans-4-hydrocyclohexyl) - -benzylamine. Melting point: 246-248 ° C.

Example VI. 3-bromo-2-butyryloairiino-5-carboeto xy-N, N-diethylbenzylamine. 3 g 2-amino-3-bromo-5-carboethoxy-N, N-diethyl-ben- The zylamine is dissolved in 30 ml of benzene and heated for ° C minutes to 50 ° C with 3 ml of acid chloride maskn wego. Concentrate in a vacuum to dryness and clean the residue by chromatography on silica gel (euent: benzene acetate v = 6: 1). You get 3-bar mo-2-butyrylamino-5-carboetcksy-N, N-diethyl-benzy- loamine which was converted into ethanolic hydrochloric acid leads to hydrochloride, melting point: 134 ° C.

Example VII. 2-aeethylamino-3-bromo-5-carboeto- xy-N-cyclohexyl-N-methyl-benzylamine.

Mp. Hydrochloride: 220-223 ° C Prepared from 2-amino-3-bromo-5-carboethoxy-N-cyclo- hexyl-N-methylbenzylamine and acetyl chloride analog as in example VI.

Analogously to examples 1-7, it is prepared on ^ tap dance unions: 4-bromo-2,6-bis- (pyrrolidine-methyl) - dihydrochloride -acetanilide, melting point: 319 ° C (decomposition), 4-bromo-2,6-bis- (morpholine-methyl) dihydrochloride - -aniline, melting point: 251 ° -257 ° C (decomposition), 4-bromo-2,6-bis- (piperidine-methyl) dihydrochloride -acetanilide, mp: 308-312 ° C (decomp. 40 clades). ^ N- (2-amino-5-methoxybenzyl) piperidine, oil, poly Structure theorem using IR, UV and resonance spectra nuclear, -acetyl-2-acetylamino-N, N-diethylbenzylamine, 45, mp: 102-103 ° C, 5-acetic hydrochloride> -2-amino-3-bromo-N-cyclohe- xyl-N-methyl-benzylamine, melting point: 229-231 ° C, 2-amino-3-bromo-N, N-dimethyl-5- (1-hydroxy-ethyl) 50-benzylamine, mp: 69-72 ° C, 2-amino-5-bromo-3-dimethylamine dihydrochloride nomethyl-N, N-dimethylc-benzylamine, at a temperature of melting; 284-287 ° C (decomposition), 2-acetylamino-5-bromo-N, N-diethyl hydrochloride 55-3-methylbenzylamine, m.p. 192.5- —194 ° C, 2-amino-5-bromo-N-cyclohexyl-N> 3- hydrochloride - dimethyl benzylamine, melting point: 206.5-207.5 ° C (decomposition, 60 N- (2-acetylamino-5-bromo-3-methyl-benzyl) -morphol- na, mp: 105-110 ° C, 2-amino-5-bromc-N, 3-dimethyl-N- (trans-4-hydroxy- -cyclohexyl) -benzylamine, melting point: 122-123.5 ° C, 65 2-acetylamino-5-bromo-N3-dimethyl-N- (trans-4-hy-7 droxy-cyclohexyl) -benzylamine, with a temperature of not / a: 136.5 ° -138 ° C, 2-acetylaminc-N, N, 3-trimethylbenzyl hydrochloride loamines, melting point: 162 ° C to 164 ° C, N- (2-amino-5-bromo-3-methyl-ben- zyl) piperidine, mp 176-179 ° C (schedule), 4-amino-5-bromo-3-III-order dihydrochloride butyl- -N, N-diethylbenzylamine3 melting point: 201-204 ° C (decomposition), 2-acetylamino-5-bromo-3-tertiary hydrochloride. bu- ' Tyl-N-cyclohexyl-N-methyl-benzylamine, temp melting point: 231-234 ° C, 2-amino-3-bromo-5-III-rcd hydrochloride. butyl-N- -cyclohexy-N-methyl-benzylamine, m.p. temperature: 214 ° C -215 ° C (decomposition) and N- (2-amino-5-bromo-4-tertiary butyl hydrochloride) -benzyl) -pyrrolidine, mp: above 190 ° C (decomposition), N- (2-acetylamino-5-bromo-4-tertiary butyl benzyl) - -piperidine, mp: 132-134 ° C, 2-acetylamino-5-bromo-N-cyclohexyl-N-methyl-3- - (N-methyl-cyclohexylaminomethyl) benzylamine, o boiling point: 194-199 ° C, 2-acetylamino-5-bromo-4-III-order. butyl-N, N-two- ethylbenzylamine, mp: 88-91 ° C, 2-amino-5-bromo-4-III-order hydrochloride butyl-N- -cyclohexyl-N-methyl-benzylamine, temp foaming: 202-202.5 ° C (decomposition), N- (2-Amino-5-bromo-4-III-order bu-) dihydrochloride tylobenzyl) morpholine, mp: 194- —198 ° C (decomposition), N- (2-acetylamino-5-bromo-4-III- dihydrochloride -before butyl-benzyl) -N'-methyl-piperazine, temp melting point: above 250 ° C (decomposition), 2-amino-5-bromo-N- (trans-4-hydroxy-cyclohexyl) -N -methyl-3- [N-methyl- (t * ans-4-hydroxy-cyclohexylam- no) -methyl] -benzylamine, m.p.: 179-180 ° C, 2-amino-3-bromo-N, N-dimethyl-5-methoxy-benzyl- amine, construction confirmed by IR, UV spectrum and nuclear resonance, 2-amino-N, N-dimethyl-5-methoxybenzylamine, poly Structure theorem using IR, UV and resonance spectra nuclear, N- (5-acetyl-2-amino-benzyl) -hexame- hydrochloride of tylenoamines, m.p .: 205 ° -207 ° C. (dec Quad), -acetyl-2-amino-3-bromo-N, N-thivumethyl-benzyl- amine, mp: 92-95 ° C, 5-acetyl-2-amino-N, N-dimethylbene hydrochloride zylamine, mp: 209-215 ° C (dec Quad), N-ethyl-2-amino-3-bromo-N-cyclohexyl-5- (1-hydro- x-ethyl) -benzylamine, m.p .: 117- -121 ° C, N-ethyl-2-amino-3-bromo-N-cyclohexy hydrochloride l-5-fluorobenzylamine, m.p .: 176- —178 ° C, N-ethyl-2-amino-5-bromo-N-cyclohexy hydrochloride l-3-fluorobenzylamine, m.p .: 193- —195 ° C, 2-amino-5-bromo-N-cyclohexyl-3-fluoro hydrochloride ro-N-methyl-benzylamine, melting point: 226-228 ° C (decomposition), 6 532 8 2-amino-5-bromo-3-fluoro-N- (trans-4- -hydroxy-cyclohexyl) benzylamine, m.p. temperature: 231-233 ° C (decomposition), N- (2-amino-3-bromo-5-fluoro-benzyl) hydrochloride - -morfokny, melting point: 230-232 ° C, 2-amino-3-bromo-N, N-dimethyl-5- hydrochloride -fluoro-benzylamine, mp: 241- -243 ° C, 2-amino-5-bromo-N, N-dimethyl-3- hydrochloride o -fluoro-benzylamine, mp: 263- —265 ° C (decomposition), 2-amino-5-bromo-N, N-diethyl-3-me- hydrochloride tylobenzylamine, mp: 177-179 ° C (schedule), N-ethyl-2-amino-5-bromo-N-cyclo dihydrochloride hexyl-3-methylbenzylamine, melting point: 183-187 ° C (decomposition), 2-acetylamino-5-bromo-N-cyclohexyl-N, 3-dimene- tylobenzylamine, mp 102-104 ° C, N- (2-acetylamino-5-bromo-3-methyl-benzyl) -pyrrole- dyne, melting point: 123 ° C to 127 ° C, N- (2-amino-5-bromo-3-methyl) -he- dihydrochloride xamethyleneamine, m.p .: 159-164 ° C (schedule), N- (2-acetylcamino-5-bromo-3-methyl-benzyl) -piper- dyne, melting point: 119 ° C to 124 ° C, N-ethyl-2-amino-3-bromo-5-carboxy-N- hydrochloride -cyclohexylbenzylamine, melting point: 227-229 ° C (decomposition), 2-amino-5-carboxy-N-cyclohexyl-N-methyl-benzyl- amine, melting point: 200 ° C to 205 ° C, N- (2-amino-5-carboxy-benzyl) -he- dihydrochloride xamethyleneamine, melting point: above 121r ° C (decomposition), 2-amino-5-carboxy-N, N-diethylbene hydrochloride zylamine, m.p .: 194 ° C to 198 ° C, N- (2-amino-3-bromo-5-carboethoxybene hydrochloride) zyl) -pyrrolidine, m.p .: 204-205 ° C, 2-amino-3-bromo-5-carboethoxy-N- (trans 40 -4-hydroxy-cyclohexyl) benzylamine, at a temperature of melting point: above 137 ° C (decomposition), N- (2-amino-3-bromo-5-carboethoxybene hydrochloride) zyl) hexamethyleneamine, m.p. 219- —221 ° C, 45 N-ethyl-2-amino-N-cyclohexyl-5-methyl hydrochloride l-benzylamine, m.p .: 189-191 ° C (schedule), 2-amino-3-bromo-5-cyano-N-cyclohe- hydrochloride xyl-N-methyl-benzylamine, melting point: 50 236-240 ° C, 2-amino-3-bromo-5-carboethoxy-N-cyclo hydrochloride hexyl-N-methylbenzylamine, melting point: 212-215 ° C, 2-amino-5-bromo-N, N-diethyl-3-tri- 55 fluoromethylbenzylamine, melting point: 198-200 ° C, 2-amino-3-bromo-N, N-diethyl-5-fluoro hydrochloride benzylamine, m.p. 182 ° C to 184 ° C, 60 N-ethyl-2-amino-3-carboethoxy-N-cyclo hydrochloride hexylbenzylamine, mp: 193- —197 ° C, N-ethyl-2-amino-5-bromo-3-carboxy-N- hydrochloride -cyclohexylbenzylamine, melting point: 65 130-140 ° C. 96 53 9 .¦ • '' '-v

Claims (8)

Patent claims A method for the preparation of new benzylamines of general formula I, wherein Rx is hydrogen, R2 is hydrogen, chlorine or bromine, R3 is fluoro, methyl is in the 3, 4 or 5 position, or when RA is aliphatic or optionally substituted an aromatic group; acyl or, when R2 is chlorine or bromine, also in the 2- or 6-position of the phenyl ring, a straight or branched alkyl group with 2 to 4 carbon atoms, a tri-bromethyl group, cyano, carboalkoxy, acetyl or 1-hydroxyethyl, carboxyl group, when at least one of the symbols R ^ R ^ R4 or R5 is not a hydrogen atom, an alkoxy group in the 3, 4 or 5 position or when R2 is chlorine or bromo, also in the 2 or 6 position of the phenyl ring, or aminomethyl of formula III where Rg and R7 are the same or different and represent an alkyl, cycloalkyl or hydroxycycloalkyl group or together with the nitrogen atom form a pyrrolidine, piperidine or morpholine ring, R4 and R5 are the same or different and represent hydrogen atoms, straight line or branched alkyl group with 1-5 carbon atoms optionally substituted with 1 or 2 hydroxyl groups, alkenyl group with 2-4 carbon atoms optionally substituted with 1 or 2 hydroxyl groups cycloalk alkyl group with 5-7 carbon atoms, benzyl, morpholinocarbonylmethyl groups or together with the nitrogen atom form the pyrrolidine, piperidine, hexamethyleneamine, morpholine, N-methyl-piperazine or camphidine ring and physiologically acceptable salts with inorganic or organic acids in that the compound of general formula 2, in which R2 -Rs have the meaning given above, is reduced and the obtained compound of general formula 1, in which R3 is a nitrile group, is optionally converted by partial hydrolysis into the corresponding carbamino compound of of general formula I and / or the obtained compound of general formula I, in which Rt is hydrogen and R2, R3, R4 and R5, except for the group containing a reactive hydrogen atom, is optionally then acylated and / or the compound of general formula I obtained, optionally it is converted into its physiologically acceptable salt with an inorganic or organic acid. 2. The method according to claim The process of claim 1, wherein the reactions are carried out in a solvent. 3. The method according to p. The process of claim 1 or 2, characterized in that the reductions are carried out with nascent hydrogen, hydrogen in the presence of a catalyst, metal complex hydride or tin (II) chloride-hydrochloric acid system, at a temperature of 0-100 ° C. 4. A method for the preparation of new benzylamines of general formula I, wherein RL is hydrogen, R2 is hydrogen, chlorine or bromine, R3 is a carbamyl group, R4 and R5 are the same or different and represent hydrogen, straight or branched alkyl group with 1-5 carbon atoms optionally substituted with 1 or 2 hydroxyl groups, alkenyl group with 2-4 carbon atoms optionally substituted with 1 or 2 hydroxyl groups, cycloalkyl group with 5-7 carbon atoms, benzyl, morpholinecarbonylmethyl or together with the nitrogen atom is the pyrrolidine, piperidine, hexamethylene amine, morpholine, N-methyl-piperazine or camphidine ring, and their physiologically acceptable salts with inorganic or organic acids, characterized by the compound of general formula 2 in which R2 - Rs are as above given meaning is reduced and the obtained compound of general formula I, in which R3 is a nitrile group, is converted by partial hydrolysis to the compound of general formula I, in which R3 is a carbamyl group and optionally converted to a physiologically acceptable salt with an inorganic or organic acid 5. The method according to p. The process of claim 4, wherein the reactions are carried out in a solvent. 6. The method according to p. The process as claimed in claim 4, characterized in that the reductions are carried out with nascent hydrogen, complex metal hydride or tin (II) chloride-hydrochloric acid at a temperature of 0 ° - 100 ° C. 7. Process for the preparation of new benzylamines of general formula I, in which R ± is an aliphatic or optionally substituted aromatic acyl group, R2 is hydrogen, chlorine or bromine, R3 is a fluorine atom, a methyl group in position 3, 4 or 5 or when R2 is a chlorine or bromine atom also in the 2- or 6-position of the phenyl ring, a straight or branched alkyl group with 2 to 4 carbon atoms, a trifluoromethyl group, a cyano, a carboalkoxy, acetyl, 1-hydroxyethyl, a carboxyl group, when at least one of R2, R4 or R5 is not a hydrogen atom, an alkoxy group in the 3, 4 or 5 position, or when R2 is chlorine or bromine also in the 2- or 6-position of the phenyl ring, or an aminomethyl group of formula III, wherein R6 and R7 are the same or different and represent an alkyl, cycloalkyl or hydroxycycloalkyl group, or together with the nitrogen atom form a pyrrolidine, piperidine or morpholine ring, R4 and R5 represent an alkenyl group with 2 to 4 atoms in gla, and their physiologically acceptable salts with inorganic or organic acids, characterized in that the compound of formula II, in which R2 - Rs are as defined above, is reduced with catalytically activated hydrogen in the presence of carboxylic anhydride, the in situ formed compound of general formula 19 wherein R x is hydrogen immediately transforms into the acyl compound which is optionally then converted to a physiologically acceptable salt with an inorganic or organic acid. 8. The method according to p. The process of claim 7, wherein the reactions are carried out in a solvent. 96,532 ch-n; MODEL 1 -R, U R. R 'ch2-n: N0 “2 2 MODEL 2 -R. XR, -R, ¦chl-n: 2 * R. PATTERN 3 LZG Z-d o in Pab. residing 246-78 on imprint 105 + 20 copies. Price: PLN 45