SU512696A3 - Method for producing benzylamines - Google Patents

Description

where is hydrogen, hydroxy or alkyl with 1-4 carbon atoms; n is an integer of 0.1 or 2; A and B are hydrogen or together form a group (K.) i,, where y is hydrogen or lower alkyl with 1-2 carbon atoms; fn is an integer 1 or 2; T is a non-branched or branched alkyl with 1-4 carbon atoms, alkenyl with 2-4 carbon atoms or cycloalkyl with 3-4 carbon atoms, or hydrogen, if RJ has the indicated values other than hydrogen, or T. is branched alkyl with 3-5 carbon atoms, which can be substituted by 1-3 hydroxyl rpyj t - an integer of 1 or 2, possessing a high vislogichikoy activity. They propose a method for the preparation of benzylains of formula I or their salts, which consists in the fact that the compound of the general formula 11) it, J, where Hot,., And - have the same meaning; II is the form of either, or the values indicated for Kit; hydrogen or the residue of carboic acid is subjected to reduction by one of the known methods. The reduction is carried out predominantly by catalytically hydration with hydrogen in the case of a hydrogen atom or hydrogen at the time of separation, obtained, for example, by the interaction of a chain metal in alcohol, for example, by reacting sodium with ethylene, at a temperature / temperature of room temperature. boiling point with interchangeable solvent. Restored. It is preferable to carry out complex metal hydride, for example sodium borate in pyridine or lithium aluminum hydride in ether or tetrahydrofuran. If in the compound of general formula II 1, if formyl or acetyl, this group is simultaneously reduced to the corresponding gishkin group and / and R - the carbonic acid radical is then split off during the reaction if the reduction is carried out with hydrogen at the time of isolation or with the complex metal hydride. Used as starting compounds of the enamide of the general formula P, for example, the interaction of the acid halide with the corresponding mines, and, if necessary, subsequent acylation. Target products are isolated by known methods in free form. The compound of general formula 1 with organic or inorganic acids can be converted into their salts, acids such as hydrochloric, phosphoric, hydrobromic, sulfuric, lactic, tartaric or maleic acids are used as acids. Example 1. N-ethyl-N-cyclohexyl-3, 5-Dibromo-2-hydroxybenzylamine. 0.4 g of N-ethyl-N-cyclohexyl-3,5-dibromo-2-oxybenzamide is boiled for 5 hours with 0.12 g of sodium borohydride in 20 MP of dry pyridine. To decompose excess sodium borohydride, acetone-pyridine is then distilled off in vacuo, the residue is separated into water and chloroform, the chloroform phase is dried over sodium sulfate and concentrated in vacuo. Purification residue is chromatographed over silica gel with ethyl acetate. Obtains an oil that is dissolved in zanol and hydrochloric acid in ethanol is converted to N-ethyl-N-cyclohexyl-3, 5-dibromo-2-hydroxybenzylamine hydrochloride, m.p. 193-194c (decomposition). Pr im e p2. M-ethyl-N-cyclohexyl-3, 5-dibromo-2-hydroxybenzyl 1 Min 1 g of β-methyl-M-cyclohexyl-3,5-dibrom-2 oxy benzyl amide is boiled for 1 hour with 0.17 g of lithium aluminum hydride in 80 ml of absolute tetrahydrofuran, cool it, carefully mix it with water, separate the precipitate, boil it with tetrahydrofuranrm, combine the solution of heterohydrofluorine and condensing it in vacuum. The residue is partitioned into; water and chloroform; the chloroform phases are dried over sodium sulfate and concentrated under vacuum. An oil is obtained which is dissolved in ethanol and hydrochloric acid in ethio e., Hydrochloride in the hydrochloride of the N-ethyl-N-cyclohexyl-3,5-dibroy-2-oxybenzylamine a- hydrochloride, m.p. 193-194 ° C (decomposition). Example 3. N-ethyl-N-cyclo: hexide-3, 5-dibromo-2-hydroxybenznlamine 2.25 g of 2-acetoxy- / -ethyl-N-cyclo Hexyl-3,5-dibromobeneamide dissolved in 30 ml absolute tetrafrafuran and, stirring, drop in a suspension of 0.8 g of lithium aluminum hydride in 120 ml of absolute tetrahydrofuran. The mixture is boiled for 75 minutes, then heated to about and mixed with water. The precipitate formed is separated and washed once with tetrahydrofuran. Combined aqueous solutions of tetrahydrofuran to remove the organic solvent from the condensate. Thus obtained aqueous solution

Extracted three times with chloroform, the combined chloroform extracts were dried over sodium sulfate and concentrated. N-ethyl-N-cyclohexyl-3,5-di-6-th-2-oxybeneyl amine is obtained in the form of an oil, which is dissolved in ethanol and hydrochloric acid in ethanol is converted into hydrochloride, m.p. 193-194 0 (decomposition).

Pr and Ie p 4. 3 5-dibromo-2-hydroxy-W- (trans-4-hydroxycyclohexyl-benzylamine is obtained by reduction of 3,5-dibromo-2-hydroxy-i - (trans-4 oxycyclohexyl) -benzamide with lithium aluminum hydride according to example 2. Tpl of hydrochloride 212-218 ° C (decomposition).

Example 5. 3,5-Dibromo-2-hydroxy-M - (trans-4-.oxycyclohexyl) -benzylamine is obtained by reduction of 2-acetoxy-3,5-dibromo.N- (trans-4-oxycyclohexyl) -benzylamide with aluminum hydride lithium as in example 3. So pl. hydrochloride 212-218®С (decomposition).

Example 6. 3,5-Dibromo-4-hydroxy-1- (cis-hydroxycyclohexyl) - | benzylamine is obtained by reduction of 3,5-dibromo-4-hydroxy-N- (cis-3-oxycyclohexyl) -benzamide with lithium aluminum hydride as in example 2. m.p. hydrochloride 21b-218 C (decomposition).

Example 7. 315-Dibromo-4-hydroxyN - (cis-3-hydroxycyclohexyl) -benzylamine is obtained by precipitating 4-acetoxy-3, 5-dibromo-1 - (cis-3-oxycyclohexyl) -benzamide with lithium aluminum hydride in example 3. T .pl. hydrochloride 21b-218 with (decomposition).

Example 8. 3,5-DibrOM-4-oxyN - (trais-W-hydroxy 3 -hexyl) benzylamine is obtained by reduction of 3,5-dibromo-4-hydroxy-N - (trans-4-oxycyclohexyl) -benzamide with lithium aluminum hydride in Example 2. M.p. hydrochloride 215-215, (decomposition).

Example 9. 3,5-Dibrom-4-oxy-N - (trans-3-6xycyclohexyl) -benzyl C1min is obtained by reducing 4-aceto sy-3, b-dibromo-tranc-3-oxycyclohexyl) -benzamide with alum hydride. Anoshogichno 3 T. pl. hydrochloride 215-215 §; (raElozhenie. P r and measures Go 3,5-Dibrom-5-bk si-tert.-pentylbenzylamine,

0.8 g of 3,5-Dibromo-2-oxa-.N-tert.pentylbenzamide with O, 3 g of sodium borohydride in 30 ml of dry pyridine is heated under reflux for 5 hours. To decompose sodium borohydride, a small amount of gacheton is added and pyridine is distilled off in vacuo. The residue is dissolved in hot water 2 n. a solution of hydrochloric acid, filtered, alkalinized from 2 n. ammonia solution and extracted with chloroform three times by shaking. The organic phase is dried with sulphate, sodium fate and concentrated. For further purification, the crude product is chromatographed with chloroform (2: 1) ethyl acetate with silica gel. The resulting base is dissolved in a small amount of acetone, acidified with hydrochloric acid in ethanol, and the 3,5-dibromo-2-hydroxy-tert.-shenylbenzylamine hydrochloride is brought to crystallization by adding ether, T. c. 202-206С (decomposition from water).

Example 11.N-Ethyl-N-cyclohexyl-3, 5-dibromo-4-hydroxybenzylamine is obtained by reduction of N-ethyl-JN-M-cyclohexyl-3, 5-dibromo-4-oxybenzamide with lithium aluminum hydride according to example 2. So . hydrochloride 180181 ° C (decomposition).

Example 12. 3-Bromo-2-hydroxyN - (trans-4-oxycyclohe1 strength) -benzylamine is obtained by the reduction of 3-bp-2-propionicloxy- / N - (trans-4-bxy-. Cyclohexyl) -benzamide with lithium aluminum hydride at the same time 3. m.p. hydrochloride 194-196 with (decomposition).

Example 13. 3-Brohm-5-chloro-M-cyclohexyl-4-hydroxy- N.-methylbenzylamine is obtained by reduction of 3-bromo-5-chloro-N -cyclohexyl-4-oxn-N-methylbeoamide by lithium aluminum hydride in Example 2 M.p. 13b-138c.

Example 14. 3,5-Dibromo-N- (dioxy-tert.-butyl) -2-hydroxybenzylamine is obtained by reduction of 3, B-di6poM-, N- (dioxy-tert.-butyl) -2-hydroxybeneamide gsyumohydride lithium in example 2, So pl. 187-189 C.

Example 15. 3,5-Dnchlor-.N "- {dnoxy-tert .-- butyl) -4-hydroxy-benzyla prichgio reduced 3,5-dichloro-N - (; ixy-tert. -Butyl) -4-oxybenzamide by aluminum alum , L1№ and on. Example 2. m.p. hydrochloride 166169 C (decomposition).

 the invention

Claims (3)

1. The method of obtaining benelgminov, General formula I x "t. SN | -1G ". where is Nav - chlorine or bromine;  . - voorol, xftof№a.H sr; .Rj branched alkyl with 3-5 carbon atoms, which μsmkw to be substituted by 1-3 hydroxyl groups or a group of formula 1a Rj is hydrogen, hydroxy or where alkyl with 1-4 carbon atoms; P - integer 0,1 or 2 { and B is hydrogen or together form a group (Rj-Cl-Rsjm, where Ry is hydrogen or lower alkyl with 1-2 carbon atoms; m is an integer of 1 or 2; T (is a meta-branched or rae branched alkyl with 1-4 carbon atoms, alkenyl with 2-4 v atoms or cichlosyl alkyl with 3-4 carbon atoms, or it can be hydrogen, if JRj has the above values, except hydrogen , or I, branched alkyl I with 3-5 carbon atoms, which can be zeyen et 1–3 hydroxyl groups; .. is an integer of 1 or 2, or 1 of their salts, so that compound of general formula It .AT , where Hag, And, and t are the above); th | - formyl or acetyl ataae for  - value; e - hydrogen or the residue of karOonic acid is subjected to bbc becoming one of the known methods, followed by isolation of the target product in a known manner in a free-form or as a salt. 2. The process according to claim 1, wherein the process is carried out in a solvent, for example, pyridine, ether, or tetrahydrofuran. 3. A method according to claims, 1.2 o tl and h ayu and with the fact that the reduction process is carried out catalytically if R is hydrogen, catalytically or xlex metal hydride, if .and - hydrogen or a carboxylic acid residue, at a temperature up to three seconds after the solvent is applied. . Priority signs 9473 with H E-chlorine or bromine; I - hydrogen, or bromine; Rj is a group of the formula (JaT; Yui R is {starting compound of the formula P) -d linear or branched alkyl with 1-4 carbon atoms, alkenyl with 2-4 carbon atoms or cycloalkyl with 3-4 carbon atoms, or hydrogen; , t is an integer i or 2 26,04,73 with Ei | - (starting compound of formula II) - formyl or acetyl; ; I "(starting compound of the formula I) is hydrogen or a carboxylic acid residue; 09/17/73 with - branched alkyl with 3-5 carbon atoms, 35 which can be substituted by 1-3 hydroxyl groups.