SU334689A1 - - Google Patents

Description

METHOD OF OBTAINING PHENILALKYLAMINOUANIDINE

The invention relates to the production of new substances that can be used in mediation.

A method for the preparation of phenylalkylaminoguanidine of the General formula

NH

# A-NH-NH-C # 2

 A is a straight branched alkylene group with two or three carbon atoms; RI and Ra -, halogen, methyl, ethyl, methoxy - or it is ksn groups a, and Hi and R2 can be the same or different, or its salt. These compounds act as blood pressure depressors and in this respect are superior to other compounds of antihypertensive type: pa. Thus, their use enriches the range of medical npenapaTOiB.

The method consists in the fact that phenylalkylidene aminoguanidine or phenylalkenilide "aminoguanidine of the general formula

where A is an alkylidene or alkenylidene group;

RI and Rs have pokazapie values, or its salt is hydrogenated with hydrogen in the presence of a catalyst, such as an Adams catalyst, in an organic solvent medium, followed by isolation of the target product as a base or salt by conventional methods. Example 1. Weigh 85 g (0,625 mol)

aminoguanidine carbonate with 1200 ml of water and diluted (1: 1) nitric acid is added to the suspension with stirring until it reaches pH 3. The mixture is treated with 300 ml of ethyl alcohol and the resulting solution is heated to reflux. Then, a hot solution of C 81 g (0.625 mol) of fanylacetaldehyde in 1000 ml of ethyl alcohol is stirred for 1.25 hours, after which it is heated again under reflux for 2 hours

when mixing. The reaction mixture is evaporated in a vacuum to a volume of about 1000 ml. Upon cooling, rhombic whitish crystals are released. After recrystallization from ethyl alcohol / dinopropyl

of ether and treatment with decolorizing charcoal, (3-phenethylidene and the lamprey anidinium nitrate with mp 156-157 ° C, yield 90% of theoretical. 11 g (0.046 mol) of this salt is dissolved (are

at room temperature and at normal pressure, using 0.25 g of Adams catalyst. After the theoretical amount of hydrogen gas is absorbed, the catalyst is filtered off, the filtrate is heated in a water bath and mixed with diisopropyl ether. Upon cooling, 9.8 g (89% of theoretical) of p-phenethylaminoguanide nitride, which, after crystallization from ethyl α-alcohol / diisopropyl ether, melts at 145 ° C, is released.

The semi-oxalate of this base is melted at 213-214 ° C — decomposition (from aqueous alcohol), the hydrochloride at .114–121 ° C (after propylation, propyl alcohol / diisopropyl, m ether), the semi-carbonate — at 109 – yoke with decomposition ( from ethyl alcohol / diisopropyl ether) and hydrobromide - at 119-120 ° С (from tropyl alcohol / diisoprapyl ether).

Example 2. A solution of 34.25 g (0.25 mol} of amino-guanidine nitrate in a mixture of 250 ml of 93% ethanol and 50 ml of water is heated under reflux, after which a solution of 37.4 g (0.275 mol a) cinnamic aldehyde in 150 ml of 93% alcohol. The reaction mixture is heated for another 3 hours with reverse X0v pump. After concentrating the reaction mixture in a thin-layer rotary evaporator, 51.8 g (83% of the theoretical) N-phenylpropenylidene - (M-guanyl ) - hydrazononitrate as light yellow needles melting at 194-195 ° C with decomposition. Suspension 39 g (0.155 mol} of this compound in 1000 ml of absolute alcohol is hydrogenated using 0.5 g of catalyst at 45 ° C until the absorption of hydrogen ceases. The reaction mixture is filtered from the catalyst and the filtrate is evaporated in a thin rotary evaporator to dryness. 38.2 g are obtained (98 % of theoretical) f of nilpropyl 1 minogue of nitdinitrate as a white powder with mp 72-76 ° C; after recrystallization from ethyl alcohol / diisopropyl ether so pl. 81-84 ° C.

Example 3. o-Methylbenzyl bromide is converted into y-o-tolylpropanol with magnesium and then ethylene oxide, which is oxidized with sodium bichromate and concentrated sulfuric acid to y-o-tolylpropinic aldehyde. 37 g (0.25 mol} of the latter are added within 45 minutes to a solution of 32.9 g (0.24 mol})

aminoguanide nest in a mixture of 50 ml of water and 95% alcohol, heated under reflux. After additional heating under reflux for 2 hours, the solvent is distilled off in a thin-layer rotary evaporator and the solid white residue is taken up in ether. In this way, 54.7 g (86% of the theoretical) of UTOTH or propyl-idb are obtained; noguaiidi.nnitr ata in the form of an amorphous powder, melted

at 150-158 ° C. This compound. After a single recrystallization from water / iso. PROPYLO. YOUR alcohol melts at 169-17GS (with decomposition).

A suspension of 21.1 g (0.079 mol} y-o-tolyl propyl or deaminoguangdium and nitrate in 500 ml of absolute alcohol is hydrated using 0.5 g of Adams catalyst until the absorption of hydrogen ceases. After filtering off the catalyst, the reaction mixture is concentrated on a thin-layer rotated ion evaporator. A white solid is obtained in the residue, it is weighed in diisopropyl ether, the suspension is filtered and the residue is dried.

Get 16.4 g (77% of theoretical) of the white drug tolylprolylaminoguann. Dinitrate with t. L. 121-125 ° C, which, after two-double-sided lerecrystallization from isopropyl alcohol and heated with coal, melts three 126--129 ° C. Similarly, other compounds are obtained, given in the table. The subject of the invention. A method for producing phenylalkylaminogonidine of general formula A-NH-NH-C-NH2 where A is an alkylene group with two or three carbon atoms; Ri and R2 are hydrogen, haloes | D, methyl, ethyl, methoxy or ethoxygrut, or a salt thereof, characterized in that phenylalkylidenamide or phenylalkenylideneminoguanidine of the general formula NH A N-NH-C-NH2 where A is an alkylidene or alkenylidene group; RI and Hz have the indicated values, or its salt is hydrogenated with hydrogenolol (Presence of a catalyst, for example, Adams catalyst, in an organic solvent medium, followed by isolation of the desired product in the form of salt or salt by conventional methods.