SU583741A3 - Method of preparing benzylamine derivatives or salts thereof - Google Patents

Claims (2)

-di1 h; 1oid) -benzyls)) Goiipcha with N-a.ich lcnklogsK1; and; | ami (10M (or rj -iiJiKJi / iaviHHOUHKJii) hexiol) nsJUBoanr B P1:. , and IIO-3 {or 5) halide ™ (or Za5 dihalide) is an alcohol of alcohol with TM-alkylShP.lo-1-sil. amine {or N-alkylaminocyclohexaiol in the presence of a fatty acid. The first option does not require the use of a fatty cell, but in the second it is necessary to take it to accelerate the reaction. As such an accelerator, preferably using acetic acid o, H-oil, KSOMacn.nHjiOj valeric, isovalerium, trimmw :; Acetic acid, caprone acid JcanpHFiosyfo acids The action of fatty acids used in the pre-cloak method consists in the amniogroup E amino-3 (or 5) -haloyl or (3,5-dihalide) benzyl alcohol and in the condensation reaction root, the benzyl alcohol the alcohol of general formula 1 can be easily reduced by reducing the corresponding halogen ™ of minic acid or its ester or by halogenating 2 ™ of amide benobyl alcohol followed by ecmi; by acetylating the amino group of the obtained compound. The condensation of a benzyl alcohol derivative with a derivative of shsglohexylamine is carried out by mixing E. heating the mixture of compounds in or without an inert solvent and, if necessary, with the presence of a fatty acid, is preferably used as an inert solvent. tetralin or xylene. The reaction is carried out at C ,. hydrophobic acid (0 at C. After testing the condensation, the excess of the cyclohexyl amine derivative, organic solvent or liquid) is removed from the reaction mixture. The residue formed is optionally deacetylated with mineral acid, Lmermer M-Methyl N ™ C ., 5-dibromobeneyl) cislohex 1lamig-g (. "Hydrogen sulfide salt). 3.0 g (0, ОО9 mol) 2 acetylamine (, 5-dibromobenzyl alcohol (m.p., C, and 1.2 g (0, O1 mol) M-methylcyclohexipamine add 0.10 ml of tetralin. And rfepeM a sew 4 hours at 170–18 ° C. Then the tetral n is removed from the reaction mixture, thus obtaining 4.1 g of ocTBTKas. The latter is added to 10 ml of concentrated acid and stirred at room temperature until the solution is complete. 80 ml of water and poromery. 1 hour at С „j iaoBiiBUiHecH crystals are filtered B, u; yiiJHB; iii T, And there are 3.2 g. Whole of the product,), a 8i,. (From theory), t pl ,, 2f С (with times,). Received) with Wash with auoTUinjM, dissolve in ipops and uonoj are treated with activated charcoal and cj) filtered. After cooling the filter: 1 g get 2.0 g of the clear. puppy white product, t, pl. 232 234Г (with Raal.) Found,%: C 40.62, H 5.05; B 39.23; C1 8.39; Mb, 58. C, (, HjiBrgCtNa. Calculated, Jo; C 40.75; H 5, O9; Br38, 76; Sy 8.61; 3 6.79; Example 2, b-Methyl-N - (3 5 dibromo 1zyl} cyclohexyl (1 (mercuric salt), 8 g (0.025 mol) 2 acetylamino-3, -dibromobenzyl alcohol is added to 15 g (0.132 mol) of N-methylcyclohexyl amine and stirred for 5 hours at 165 C. Then from 10 g of N-methylcyclohexylamine is obtained under reduced pressure, and 12 g of residue is obtained. The latter is treated as in Example 1, 8.3% of the desired product is obtained, mp 232 234 C (disassembled). 5 g t in 30 ml of water, to the mixture by adding kzt 10 g of a 47.5% aqueous solution of caustic n melt and mix 30 mip at 40--60 C. The resulting oil-like layer gradually crystallizes with; this gives 4.4 g of crystals, Te p; l 50-53 C; After recrystallization of benzene and ethanol, white crystals are obtained, Tc P.LE 54 C Prize, M-Methyl N (2 amino 5 -brombenzyl) -cycloxylamine {chloroisobutylnodal salt), 3.0 g (Os012 mol) 2 acetylamino 5 1 bromobenzyl alcohol (t, rc. C) is added to 10 g (O.088 mol) of C mesyl cyclohexylamine; 2 is stirred for 5 hours at C. Then the reaction mixture is removed with 7.5 g of N-methylcyclohexyl amine and 5.1 g of residue is obtained. The latter was washed with water, dissolved in 15 ml of concentrated hydrochloric acid, stirred for 30 minutes at C, the solution was discolored by adding 1OO ml of water and O., 5 g of activated carbon, and then filtered. After concentrating the filtrate, acetone is added to it. The crystals formed are filtered and dried. Semi-teaTrZ.Z.g target product, so pl. 2O521O C (with decomp.), Yield 78.8% (from theory). After recrystallization of ethanol from ethanol, they are obtained which melt at 211-215 C. Found,%: C 45.57; H 6.56; Br 20 and 18.51; N7.35. With ,,,) 2.jBrCEjNg ;. Calculated,%: C 45,52; H 6.22; Be 21.60; C1 19.19; N 7.57. EXAMPLE 4: L-Methyl-N- (2-amino -3,5-dichlorobenyl) -cyclohexylamine (hydrochloride salt), 2.4 g (0.10 mol) 2-acetylamino-3.5; - dichlorobenzyl alcohol and 1.5 g (O, O13. mol) W-fetilization IUIOhexylylamine are added to 10 ml of tetraphenol and stirred for 4 hours at 170-175 ° C. After removing the tetralin from the reaction mixture under reduced pressure, 3.2 g are obtained residue, The latter is treated as indicated in example 1, and 2.6 g of the desired product are obtained, yield 78.8% (from theory). The salt formed is recrystallized from hot water and 2.0 g of white crystals are obtained, t, pl. C. Found,% C 51.72; H 6.55; C 32.7 N 8.45. ik j Calculated, C, 51.93; H 6.49; Ql 32.92: 1Пр и ме р 5. N-Methyl-S (2 amino 3y-5-dibromobenzyl) - cyclohexylamine (hydrochloride salt), 8.0 g (0.025 mol) 2-acetylamino 3.5 -dibromobenzyl alcohol is added to 15 g (0s 132 mol) of N-methylcyclohexyl amine and stirred for 5 hours. After removing N-methylcyclohexylamine from the reaction mixture from the by-product, 12 g of residue is obtained, which is washed twice with 150 ml of hot water, dissolved in 30 m of concentrated hydrobromic acid and 200 ml of cold water is added to the solution while stirring. The crystals formed after the EU are filtered off, washed with acetone and 9.8 g of the desired product are obtained, mp 216-217 ° C. (with decomposition), code 86; 7% (from theory) The resulting salt is recrystallized from hot water and. petals, t, pl, 228-228,5 S. (with razl /). Found,%: C 37.06; H 4, Br 52.35; Ы5,95, Cjif I-l2 Вг N J Calculated,%: С 36.79; H 4.60; Bf- 52.49; N 6.13. When repeating Example 5, the difference is that (N-methylamino) is used instead of N-methyl-cyclohexyl mine. clohexanol, get (} T-methyl-N "(2, 5 dibromobenzylamino) 1 cyclohexanol in the form of hydrobromic salt, yield 82.3% (from theory) .1 Hp and measure 6, N-L1 tpl-N - (,, 5-dibrock bin iui) -ni k.Iji f-K (N4i ii, lu; i- velevoxide salt), 4, Оr residues, 1 rays) O) after beats, hl of excess N - metal chloride / hexyl / from the reaction mixture according to example 5, and) .- wash twice with 5 O ml of the first liquid. then 30 ml of water are added, after which 1.5 g of uvic acid dihydrate are added to it and the mixture is stirred at 70-80 ° C for 1 hour. After gradual crystallization of the formed oily substance, 3.3 g of powdered crystals are obtained. 182183 With (with decomp.), The output of 66.5% (from theog-ii). Found,%; C 41.35; H 4.83, Br 34.19; N 5.90, C, gH22bt.jN20 C 41.22; H 4.72, W Calculated,% 34.30; N6.01, Example, N-Methyl-M- (2 amino-3; 5 dibromobewsyl) cyclohexylamine (hydrogen chloride salt). 3.1 g; (0.01OMol) 2 diaceti. , 5-dibromobenzyl alcohol, M.p.-, 15 ° -152 ° C) is added to 10 g of KO, 088 mol) N-methylcyclohexylamine and nepfbieiuHBawT for 5 hours at 160-17 ° C. - 4.5 g of residue are obtained in the I-tion mixture, which is treated as in Example 1, 3 O g, M-methyl-M- (2-amino-3,5-di-bromobenzyl) -cyclohexylamine is obtained in the form of a hydrogen hydrogen salt, t. square 232-234 C (with different). EXAMPLE 8 N-Methyl-M- (2 iiMHno-3, 5 dibromobenzyl) -cyclohexnlamnn (hydrochloride salt), 5.6 g (O, O2 mol) 2 "amino-3,5-dibromobenzyl alcohol and 11.3 g of (O, 1Omol) N-methylcyclohexylamine are added to 8.8 g (0.10 mol) of n-butyric acid and stirred for 5 hours at 165 C. After that, excess N-methylcyclohexylamine is removed from the reaction mixture and n-butyric acid by distillation in vacuum at a residual pressure of 10 mm Hg. Art. After washing the residue with water, 9.5 g of an oily substance are obtained. The latter is completely dissolved in 12 ml of concentrated hydrochloric acid, 1OO ml of water is added to the resulting solution and stirred. The crystals calling in are filtered, washed with acetone and dried. Obtain 7.2 g of the target product, so pl. 224 226 C (c), yield 87.2% (from theory) The salt formed is recrystallized, and it is extracted from hot water and 5.0 g of crystals are obtained, m.p. 232-234 C (with different). Example 9 N Methyl-M- (2-vviino-3,5-dibromobenzyl) -cyclohexnlamiya (hydrochloride salt), 5.6 g (0.02 mol) of 2-amino 3.5 ibrom of benzyl alcohol and 11.3 g (ODO mol) N-methylcyclohexylamine is added to 7.4 g (O, 10 mol) of propionic acid and stirred for 5 hours at 167-170 ° C. For-. In this way, an excess of N-methylcyclohexylamine and pro-tonic acid is removed from the reaction mixture in vacuo and 9.0 g of oil are obtained. After treatment of this substance according to Example 8, 5.4 g of c & of the left product, yield 65.5% (from theory), 5.8 g of this salt in solution in 50 ml of water and 10 g of 47% pure sodium hydroxide solution are added to the solution. After gradual crystallization of the resulting oily layer, 4.4 g of N "-methyl-N- (2-amino-3,5-dibromobenzyl) -cyclohexylamine are obtained, m.p. 54 C (from benzene and ethanol). An example. N-Methyl MC2-.ami "but 5-bromobenzyl) -cyclohexylamine (Hydrogen Salt; Hydrogen Salt). 4.1 g (0fl2 mol) of 2 amino-5-bromobenzoyl alcohol and 5.7 g (0.05 mol) of Nm tylcyclohexylamine are added to 3.0 g of acetic acid and stirred 6 Io at 165-170 ° C. Then, from the reaction mixture, an excess of N-methylcycloheX silylene and acetic acid is removed and 5.6 g of the expected product are obtained, t, mp. 211 {cx,) (from ethanol), yield 74.4% (of theory), G | 1 example 11. N -MeTHJ -N- (2-amino-3 5 Dichlorobenzyl) -cyclohexylamine (hydrogen chloride salt). 1.9 g (0.01 mol) of 2-amino-3,5 dichloro benzyl alcohol, 1.5 g (0.013 mol) of methyl cyclohexylamine and 1.0 g (0.017 mol) of acetic acid are added to 10 ml of traline and stirred for 5 hours at 175 ° C. After removal of teggralin i from the reaction mixture, 3.5 g of the residue are obtained. The latter is treated as indicated in Example 8, and 2.5 g of the title compound are obtained, mp. 224-225 C (out of water), yield 78.1% (from theory). Example 2. N-Methyl- (2 amine1 -3,5-dibromobenzyl) -cyclohexylamine (hydrochloride salt), 5.6 g J0.02 mol) 2-amino-3,5-DI broc) benzyl alcohol and 11, 3 g (0.10 mo of N -methylcyclohexylamine is added to 8.88 g (0.10 mol) of isobutyric acid: the mixture is stirred for 8 hours at 150-155 ° C. After cooling, the reaction mixture is poured into water. The resulting oil completely dissolved in 20 m of hydrobromic hydrobromic acid and 100 ml of hungry water are added to the solution with stirring. The precipitated crystals are filtered off and washed tone and dried. Obtain 7.5 g of the desired product, t, pl. C (with decomp.) from water. EXAMPLE 13, N-Ethyl-} - (2-amino 3,5-dibromobenzyl- a) cyclohexylamine 5.6 g (0.02 mol) of 2 amino-355-dibromobenzyl alcohol and 6.4 g (0.05 mol) of M-ethylcyclohexylamine added to 3.0 g (0.05 mol) of acetic acid and stirred for 5 hours at 180 s. After cooling, the reaction mixture is poured into 50 ml of water and the oily layer is separated from the solution. After that, the oily layer is washed with 10% sodium hydroxide solution, water, and extracted with benzene. The benzoic extract is dried over anhydrous Naari sulfate and distillation in a vacuum. Obtain 4.5 g of the desired product as colorless; oily product t Kip, 235-240 C / 0.1-0.2 mm Hg. Art. Claim 1, A method for producing benzyl amine derivatives of the general formula: where X is C, VG Y is H, CE, Br - H. CHj R-CH, CjHg, or their salts based on cyclohexyl-silumin derivatives, characterized in that, in order to simplify the process, benzyl alcohol derivatives of the general formula. where X CE, Bg, a, Br V V nW-And Ac is condensed with derivatives with cyclohexyl amine of the general formula 9iO where in. and E is as defined above, 2-H, CHj; R -CI-Ij, S1. Ls at and isolate the target products in the form of the Basis that both radicals are e. e. vania or in the form of a salt. i mean hydrogen, 2. The method according to p. 1, distinguishing-04.07.72 when V n W - hydrogen, that. if V and W are hydrogen, nptx 5 isstoch1, information taken in mon, mon The process is carried out in the presence of a lower fatty examination: acid. Priority signs: 1. GDR patent number 74279, C 07 C ZO.OZL2 at X - Ct, Vg, Y-OY, CE, VG (12o, 25), 07.07.70. 583741.