SU503508A3 - The method of obtaining-bis / -oxy-aryl ethyl diaminoalkanes - Google Patents

Description

(54) METHOD OF OBTAINING N, N-BIS- (p-OKCIAPILETHYL) DIAMINAL ALKANES

in which R is hydrogen or an acyl group,

R2 is hydrogen or OR-rpynny,

Rs is a lower oxyalkyl group or one of the groups of the following structure -NH- -CO-R., -NH-SOs-Rs, -CH2-NH CO-R4, -CHN-NH-SOa-Rs or

—CH2 — NH — CO — NHR4, wherein R4 is hydrogen or a lower alkyl group, Rs is

AT,

Ar-CH (OH). F-C- (H2): f C- "E.7 Hf-CH (OH) -Ar.2

1 R

where Ar2 is an Ari radical in which the phenolic hydroxyls are free or protected by cleavable hydrolysis, alcoholysis or hydrogenation with protecting groups,

Ry is hydrogen or a hydrogenatively cleavable radical, predominantly substituted, for example, a benzyl radical,

RI and m are as defined,

introduced into the exchange decomposition reaction with a compound of general formula III

H-Q

where Q is hydrogen, hydroxy or alkoxy,

followed by isolation of the desired product in the form of a base or salt, in the form of a racemate or an optically active antipode by known methods.

In the case where, in Compound III, Q is hydrogen, the reaction is carried out in the presence of a hydrogenation catalyst. If Q denotes a hydroxyl group, the reaction is carried out in the presence of an acidic catalyst and, if Q is an alkoxy group, the reaction is carried out in the presence of a basic catalyst.

In case the target products obtained according to the proposed method are racemates, they are divided, if necessary, into optic antipodes. If necessary, the initially obtained free bases are converted into salts of acids, the initially obtained salts of acids into free bases or salts of other acids.

Example 1. A solution of 2,5-dimethyl-2,5-diaminohexane in acetonitrile in the presence of sodium carbonate is introduced into an exchange decomposition reaction with a double molar amount of 3.5-dibenzyloxy-a-bromoacetophenone (mp 83-86 ° C) and then in ethanol is reduced with sodium borane. 5 g of the thus obtained M, M-bis- (3,5-dibenzyloxy-p-oxyphenethyl) -2,5-dimethyl-2,5-diaminohexanedigndrochloride (mp 180-185 ° C) is hydrogenated as a solution in 125 ml of methanol on Rene nickel as a catalyst at normal pressure and room temperature. After separation from the catalytic alkyl group or lower dialkylamino group, Rg is hydrogen, amino, or hydroxy,

X is chlorine or bromine,

Y is chlorine, bromine or hydrogen, and l is a five- or six-membered saturated or unsaturated cycle.

The method according to the invention consists in that the compound of the general formula II

TO,

one

of mash and solvent (in a small amount of ethanol at the nominal level of ethereal hydrochloric acid), by adding acetonitrile, N, lN-6Hc- (ip, 3,5 - trioxyphenethyl) -2,5-dimethyl2,5-dynamohexane dihydrochloride are obtained, which

after recrystallization from 1 n. hydrochloric acid melts at 275-279 ° C.

Example 2. By the reaction of disintegrating decomposition of 4-benzyloxy-3-carbomethoxy-a-oro-mazotofenone with 2,5-dimethyl-2,5-diamino-escan in a solution of acetonitrile, N, N-6nc- (4-bepsyloxy-3-carbomethox-oxo-phenethyl) is obtained ) -2.5 - dimethyl-2,5-diaminohexanedihydrochloride (mp 133-138 ° C), from which N, N-6nc- (4-6eHsyloxy-3-carbomethoxy-) is obtained by reduction with sodium borane in ethanol - oxyphenethyl) -2,5 dimethyl-2, 5-diaminohexane (t. pl. 119-). 1 g of this compound is dissolved in 50 ml of tetrahydrofuran, but is added dropwise to 500 ml of tetrahydrofuran, 7 g of sodium aluminum hydride is added at 20 ° C, cooled with ice and then thrown over 3 hours with a reverse refrigerator. After decomposition with water and withdrawn on the filter, it is unary. Crystal crystals are called; S, M-bis- (4-benzyloxy - 3-hydroxymethyl- | 3-hydroxyphenethyl) -2,5-dimethyl - 2,5-diaminohexane (mp. 129-132 ° C, from methanol) .

The resulting product in the form of a solution in isopropanol with the help of ethereal hydrochloric acid is converted into digindrochloride (mp 205-208 ° C). 4 g of this compound is hydrogenated in 100 ml of methanol and 10 ml of water at a pressure of 1 atm and 20 ° C using palladium on carbon as a catalyst. After removal of the catalyst and solvent, N, N-6Hc- (ip, 4-dioxy-3-hydroxymethylphenethyl) -2,5-dimethyl-2,5-diaminohexanedihydrochloride is crystallized out. The product is recrystallized from a mixture of water with acetonitrile (mp. Above 350 ° C).

Example 3. 4-Benzyloxy-3-carbomethoxy-bromoacetophenone is subjected to the reaction of exchange rasnol.enn with N, M-dibenzyl-1,6-diaminohexane and get K, N- (benzyloxy-3-carbomethoxy-p-oxofenethyl) -Y, M - dibenzyl-1,6-diaminohexanedihydrochloride (mp. 108 ° C, from acetonitrile), which according to example 2 is reduced with lithium aluminum hydride to N, 1-bis- {4-benzyloxy-3-hydroxymethyl (3-hydroxyphenethyl) - N, M-dibenzyl - 1,6-diaminohexane. 37 g of this base is hydrogenated in 600 ml of methanol at 50 ° C and a pressure of 5 atm, using palladium on carbon as a catalyst. After suctioning the catalyst on the filter, the methapole solution, cooled with ice and stirred with concentrated sulfuric acid, is adjusted to pH 5.5. 1, M-bis- (p, 4-dioxy-3-hydroxymethylphenethyl) -1,6 - diaminohexanesulfate is crystallized. The product is recrystallized from water (mp. Above 350 ° C). Example 4. A mixture consisting of 34 g of 3-benzyloxy-a-bromoacetophenone, 18 g of N, N-dibenzyl - 2,5-dimethyl - 2,5-diaminohexane (b.p. at 0.05 Torr 167-168 ° C), 15 g of sodium carbonate and 125 ml of acetonitrile are heated under reflux for 4 hours. After suctioning off on the filter and evaporation, N, N-6nc- (3-benzyloxy-3-oxofenethyl) -N, N - dibenzyl-2,5-dimethyl-2,5-diaminohexane is obtained, which is hydrogenated in 250 ml of acidified ethereal hydrochloric salt. acid methanol in the presence of palladium on carbon as a catalyst at 60 ° C and 5 atm. After removal of the catalyst and solvent, N, N-6nc- () p, 3-dioxyphenethyl) -2,5-dimethyl-2,5-diaminohexane dihydrochloride is crystallized out. After recrystallization from water, the final product has a melting point of 20 ml. 270-273 ° C. Example 5. By the exchange decomposition reaction of M, M-dibenzyl-2,7-dimethyl-2,7-diaminooctane with a double molar amount of 3,5-dibenzyloxy-a-bromoacetophenone as a solution in acetonitrile in the presence of sodium carbonate, S is obtained N-bis- (3,5) -dibenzyloxy - p-oxyphenethyl) -N, N - dibenzyl2, 7-dimethyl-2,7 - diamio-octane dihydrochloride

Ari-CH (OH) -C% -NH-C- (CH-C-NH-CH.: -CHiOH )-Ar in which RI is hydrogen or a methyl group, t is O or an integer from 1 to eight,

PV,

Claims (3)

K, (t. Pl. 170-172 ° C), which with help, and sodium borane is reduced to N, N-bis- (3,5benzyloxy- | p-oxyphenethyl) - N, N-dibenzyl2, 7-diaminooctane ( mp 108-110 ° C). The resulting base is hydrogenated in glacial acetic acid with POMOSH.I palladium on coal at 50 ° C and 5 atm. The crystals obtained after recrystallization from ethanol, suctioning off on the filter and evaporation are dissolved in hot water and mixed with hot, sulphate of sodium sulphate. When cooled, crystallize C, B-bis- (p, 3,5-trioxyphenethyl) -2,7-dimethyl-2,7-diaminooctane sulfate (mp. 245 ° C, from water). Example 6. In accordance with Example 5, the following compounds were prepared: N, N-6Hc- (2-chloro-p-oxyphenethyl) -2,5-dimethyl-2, 5 - diaminohexanedihydrochloride, m.p. 247-249 ° C; N, .N - bis- (| p, 4-dioxy - 3-methanesulfonamidophenethyl) -1,4 - diaminobutane dihydrochloride, t. Pl. 226-227 ° C; N, N-bis- (p, 3,5 - trioxyphenethyl) -1,6 - diaminohexapsulfate, so pl. 283 ° С (with decomposition); N, N-6nc- (3,5 - dichloro-p, 4-dioxyphenethyl) 1, 6-diaminohexanedihydrochloride, t. Pl. 208–209 ° С (with decomposition); N, N - bis- (p, 4-dioxy-3-dimethylaminosulfonamidophenethyl) - 1,8 - diaminooctane dihydrochloride, so pl. 185-186 ° C (with decomposition); S, K-bis - (: p, 4 - dioxy-3 - methanesulfonamidophenethyl) - 1,6 - diamipohexanedihydrochloride, so pl. 250 ° C (with decomposition). The invention The method of obtaining N, N-bis- (p-hydroxyarylethyl) diaminoalkanes of the general formula Ari means one of the radicals of the following structure RO or RO in which R is hydrogen or an acyl 45 group, Ra is hydrogen or OR-rpynny, Rs is a lower oxyalkyl group or one of the groups of the following structure -NH- -CO-R4, -NH-3Gr-Rs, -CHA-NH- -CO-R4, -CHN-NH-SOs-Rs or -CHN-NH-CO-NH-R4 and R4 means hydrogen or a lower alkyl group. 7 Rs is a lower alkyl group or a shuya dialkylamino group; Re is hydrogen, an amino or hydroxy group, X is chlorine or bromine, Y is chlorine, bromine or hydrogen. ,, I1 CH (OH) -CH-i-imf-C- (CH2); JC-lJR-CH.rCH (OH) Ar2 R where AGg is an Ari radical in which the phenolic hydroxyls are free or protected by cleavable hydrolysis, alcoholysis or hydrogenation with protecting groups, R / is hydrogen or a cleavable radical, predominantly substituted, for example, a benzyl radical, RI and m are as defined, introduced into the reaction of the decomposition with a compound of the general formula Nq where Q is hydrogen, hydroxy or alkoxy. A is a pi or six membered saturated or unsaturated ring, characterized in that the compound of the general formula and one With the subsequent isolation of the target product in the form of a base or salt, in the form of a racemate or an optically active antipode by known methods. 2. A method according to claim 1, wherein the reaction is carried out in the presence of hydrogenation catalysts, if Q is hydrogen. 3. The method according to claim 1, wherein the reaction is carried out in the presence of an acidic catalyst, if Q is an oxy group, and preferably in the presence of a basic catalyst, if Q is an alkoxy group.