SU416941A3 - Method of producing 9,10-dihydro-9,10-ethaneanthracene - Google Patents

Description

The invention relates to a method of obtaining new, not described in the literature, treadio-anthracene, which have pharmacological activity and can be used in medicine.

A known method for producing ethano-aptracenes of the general formula

Qlk-am

where X is a chlorine atom or hydrogen;

alk-lower alkylene residue;

Am is a substituted amino group,

by catalytic hydrogenation of 9, W-dihydro-9, 10-ethano- (1,2)-anthracene, which in the 9 position has a residue translatable into the amino group.

However, in the literature there is no information about the methods of obtaining new 9, W-Dihydro-9,10 ethanoanthracene with cores of the general formula I

one(

“HH

having an aminoalkyl residue in the 9-position, and in one of 1-8-free-free or acylated oxygrune, having valuable properties.

A method for the preparation of 9,10-dihydro9, 10-ethanoanthracene of the general formula I or its salts is proposed, which consists in that in 9-X-9,10 dihydro-9, 10-ethano-11tracene, which has in one of 1-b-free or acylated oxygroup and where X is translatable

in the amioalkyl group, the residue is translated

the residue X in the aminoalkyl group is known by the molecular method.

The residue X is, for example,

an alkyl residue substituted by a hydroxyl group Z, reactively esterified into an ester. A hydroxyl group Z, esterified to ester reactively esterified, is an example, a hydroxyl group that has been esterified into an ester with a strong organic or inorganic acid, in particular, a hydrochloric acid, such as chlorine -, bromo- or iodo-hydrogen, OR arylsulfonazole acid, for example / g-toluenesulfonic.

The conversion of the residue Z to an amine group is carried out, in particular, by reacting with an amnn, for example ammonia or methylamine.

The exchange reaction is carried out in the usual way, with stpeino in the presence of pi-iiC .iH and in the corresponding case in the presence of a condensing agent, preferably at an elevated temperature and in a corresponding case under pressure.

G revr; pzenie residue Z in the primary or vtorpchuk; amiponuyu group can be carried out by means of iKianMo / iciicIVIJA with M (j4eBnnoi i or, correspondingly, | () L, C-dp: American urea.

The residue X can also be converted by reduction to an aminoalkyl group. Such residues are, for example, the corresponding carba.mil or carba.mylalkyl groups, the corresponding acylaminoalkyl or carbalkoxyamidoalkyl groups.

Restoration is carried out in the usual manner, in part with an amidium reducing agent, such as magnum aluminum hydride or iodo borohydride in a tertiary amine, e.g. pyridium or triethylamine, or in aluminum hydride or diborane.

Reducing agents can also be used with activators, for example aluminum chloride. If the starting materials contain apyloxy groups, they can be simultaneously split into free hydroxy groups. In this case, loss of viscosity can be carried out electrolytically on cathodes with an overvoltage (high), for example, mercury, lead alumine or lead. As a catalyst, for example, a mixture of water, sulfuric acid and a lower alkanecarboxy acid, such as acetic acid or propioic acid, is used. The anodes can consist of platinum, coal, or svitsa, and as anolyte they play an advantage with sulfuric acid.

The residue which is transferable to an amioalkyl group is a residue corresponding to the indicated aminoalkyl group, in which nitrogen is bonded to one of its substituents by a double bond and, in appropriate case, carries a positive charge, or where one of the atoms linked to nitrogen atoms carries a hydroxyl group. i.e., an imino-or imi-alkyl radical or a corresponding amino or ammonium alkyl residue, where the amino group is bonded to one of the amio substituents by a double bond.

The translation is carried out in the usual way by restoring, for example, an azomethine bond. Restoration is carried out in the usual way, preferably with hydrogen in the presence of a catalyst such as platinum, palladium or ipkelic, and also with formic acid. The Schiff base can also be reduced with an alkali or p hydride of the earth-metal, for example, boron patry or lithium aluminum hydride. If the starting materials contain aniloxyl groups, they are simultaneously decomposed into free hydroxyl groups, for example, lithium aluminum hydride.

Another residue which is converted by reduction to an aminoalkyl group is, for example, also a K-non-essential; or N-amino-substituted aminoalkyl residue, a residue at the nitrogen atom;

V, o-iine i,: i5i (Mbiii by restoring. 0t .ii, iiioieiUic propod g by restoring

good way.

The advantage is an a-aralkoxycarbonyl residue, such as carbobenzoxy residue, which can be split off by hydrogenolysis, in particular by reduction, for example, with hydrogen in the presence of a hydrogenation catalyst, such as palladium or platinum. Y may also be a p-halogenoalkoxycarbonyl residue, for example a 2,2,2-trihaloethoxycarbonyl, such as a 2,2,2-trichloroethoxycarbonyl, or a 2-monoiodoxycarbonyl residue, which can be removed by reduction. Hydrogen is preferably used as a reducing agent at a point of release, which can be obtained, in particular, by exposure to a metal or metal alloy and hydrogen-discharging agents, for example carboxylic acids, alcohols or water. Preferably nink or zinc alloys are used in acetic acid. Divalent chromium compounds such as chloride or acetate can be used.

Y may also be an arylsulfonyl group, such as a toluene sulfopyl group, which is otschenlen in the usual way, in particular by reduction

hydrogen at the time of release, for example with an alkali metal, such as lithium or sodium, in liquid ammonia.

The residue that can be converted to aminoalkyl may also be N-unsubstituted.

or N-myo-substituted amioalkyl residue, bearing an additional atom of nitrogen removed by the nitrogen atom by hydrolysis. Cleavage is carried out by hydrolytic detachment Y. The residue Y is predominantly

is an acyl residue, nanopolymer alkanoyl, preferably lower alkanoylplate, such as acetyl residue, benzoyl, phenylalkanoyl, carcaroxy residue, tertiary butyloxycarbonyl,

carboethoxy or carbomethoxy residue, or aralkoxycarbonyl residue, such as carbobenzoxy residue.

The hydrolytic cleavage of Y is carried out, in particular, by hydrolyzing agents, in particular, in the presence of acidic means of dilute mineral acids, such as sulfuric or hydrohalic acids, or, preferably, in the presence of fixed assets — alkali metal hydroxides,

Naprimer hydroxide iatri.

If compounds that in one of the 1-8-positions of acyloxy are reduced, a. lithium humic hydride, the acyloxy group can be simultaneously reduced to a hydroxyl group. If in this

If it is desirable to obtain a compound containing an acyloxy group, then the hydroxyl group obtained can be acylated in a known manner.

The desired product is isolated in a known manner as the base or salt, as a racemate or as an optical antipode. In the thus obtained target products - N-ne-substituted or L-monosubstituted amio-alkyl groups, substituents can be introduced in a known manner, for example, by treatment with a reactive ester of the corresponding alcohol.

Example 1. A solution of 12 g of L-methyl-2-hydroxy9, 10-dihydro-9,10-ethano-9-anthrylcarboxamide in 100 ml of tetrahydrofuran is added slowly dropwise to a suspension of 4 g of lithium aluminum hydride and then heated to boiling. After 2 hours, cool the reaction mixture and carefully add 4 ml of water and then 5 ml of 15% sodium hydroxide. The precipitated precipitate is filtered off and the filtrate is evaporated at vacuum. The crude 2-hydroxy-9 (methylaminomethyl) -9,10-dihydro-9,10 - ethanoanthracene remains, which melts after repeated recrystallization from isopropanol at 120-125 ° C. The hydrochloride melts at 261 - 262 ° C.

The following compounds are prepared in a similar manner:

2-hydroxy-9- (dimethylaminomethyl) -9,10 - dihydro-9, 10-ethanoanthracene;

2-oxn-9- (y-methylaminopropyl) -9,10 - dihydro-9, 10-ethazo-anthracene;

2-hydroxy-9- (1-dimethylaminopropyl) -9,10 - dihydro-9, 10-etaioantracene.

Example 2. A solution of 10 g of 2-hydroxy-9,10-dihydro-9, 10-ethano-9-anthraldehyde and 4 g of methylamide in 100 ml of methanol is heated in a refractory tube for 4 hours to 90 ° C. Then evaporated in vacuo. The residue is dissolved in 200 ml of alcohol and hydrogenated at room temperature after the addition of 2 g of Rene nickel. After the absorption of hydrogen ceases, the catalyst is filtered off and evaporated in vacuo. 2-hydroxy-9- (methylaminomethyl) 9, 10-dihydro-9,10-ethanoanthracene remains, which melts after recrystallization from isopropanol at 120-125 ° C and is identical with the product described in Example 1.

Example 3. A solution of 7 g of 2-oKCH-9- (N-6eiizylmethylaminomethyl) -9,10-digdro-9,10 - jrn anthracene in 100 ml of dimethylformamdda is hydrogenated after the addition of 8 g of palladium np (10%) at normal pressure and room temperature. After the uptake of hydrogen ceases, the catalyst is filtered off and the solvent is evaporated in vacuo. Remains 2-hydroxy-9- {methylaminomethyl) 9, 10-dihydro-9,10-ethanoanthracene, melting after repeated recrystallization from isopropanol at 120-125 ° C and is identical with the product described in example 1.

Subject invention

20

The method of obtaining 9,10-dihydro-9,10-ethanoanthracene with cores of the general formula I

25

having a 9-position of the aminoalkyl residue 1 in one of the 1-8-positions of a free or acylcated hydroxy group, or its salts, characterized in that in 9-X-9,10 dihydro-9, 10-ethanoanthracene, which in one of 8 free positions or an acylated hydroxy group, and where X is non-reducible to an aminoalkyl primer, translate said residue X in a known manner, for example, by reacting said starting product with an amino compound, followed by isolating the desired product and in the case of preparing N-unsubstituted or N-substituted with Unity of its alkylated

and is isolated in a known manner as a base or salt, as a racemate or as an optically active antipode.