SU562971A1 - Process for preparing 1-(5,6,7,8-tetrahydro-1- or 2-naphthyl)-2-alkylaminopropanols-1 - Google Patents

Abstract

METHOD OF OBTAINING 1-

Description

The invention relates to methods for producing new compounds - 1- (5 / b, 78-tetrahydro-1 - or 2-naphthyl) 2-alkylamino-propanol 1B-1 of the general formula

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having valuable pharmacological properties ..

Naphthoxy-substituted alkanolamines are known to be pharmacologically active compounds.

However, there is no information in the literature about the compounds of formula I.

A method is proposed for preparing compounds of the formula I which are of pharmacological interest, namely, that naphthalene is reacted with cd-bromopropionyl bromide in various organic solvents by reaction of Crafts liquoride in the presence of aluminum chloride, - and depending on the solvent, it is obtained: in chloroform 1- (ob-naphthyl) -2-bromopropanone-1, and in nitrobenzene -1 - ((naphthyl) -2-bromopropanone-1. The obtained 1- (or p-naphthyl) -2-brbmpropanone-1 is reacted with an excess of the corresponding alkylamine, such as isopropylamine, diethylamine, piperidine, in an environment of an inert solvent, for example benzene, the selected amino ketone in the form of hydrochloride is regenerated by catalytic conversion into an autoclave. . Skeletal nickel is used as a hydrogenation catcher. The desired product is isolated in the form of a salt, usually in the form of the hydrochloride.

Properties of the synthesized products are shown in the table.

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g Example 1 - ("/ - Naphthyl) -2-bromopropanone-1 (II (i). In a three-necked flask with a stirrer, a calcium chloride tube and a dropping funnel, 7 g (0.052 mol) of aluminum chloride and 20 ml of dry chloroform are placed. To this mixture for 30 10.6 g (5.2 ml, 0.052 mol) of bromopropionyl bromide diluted in 10 ml of dry chloroform are added dropwise with good stirring. The bath temperature is raised to 30 ° C and stirred at this temperature until the solution becomes clear, after which the temperature is lowered to room temperature. A solution of 6, 4 g of 0.952 mol of naphthalene in 20 ml of dry is added dropwise Hydrogen bromide is liberated at the same time, the bath temperature is again raised to 35-40 ° C and stirred for 30 minutes, the reaction mixture is poured into ice (150 g), 10 ml of concentrated hydrochloric acid is added and left overnight. the organic layer is rinsed with water (2-3 times and dried with magnesium sulfate. The solvent is distilled off and the resulting l- (cv naphthyl) -2-bromopropanone-1 is recrystallized from petroleum, 9 g of substance is obtained, 1- (-Naphthyl) -2-br companon-1 (11R). To 120 g (0.91 mol) of aluminum chloride in 340 ml of dry nitrobenzene with good stirring, 189 g (0.89 mol) of ot-bromopropionyl bromide in 170 ml of dry nitrobenzene are slowly added dropwise. The reaction mixture is cooled with ice before and for 1 h a solution of 110 g (0.89 mol) of naphthalene in 340 ml of nitrobenzene is added dropwise. Stirring is then continued for 1 hour at room temperature and for 1 hour at 30-35 ° C. The reaction mixture is poured onto ice, treated with 100 ml of concentrated hydrochloric acid and left overnight. Processed as indicated before. After distilling off the solvent, 1- (p-naphthyl) -2-bromopropanone is distilled under vacuum. A slightly yellowish oil is obtained, which crystallizes on standing, 1- (-Naphthyl) -2-isopropylaminopropanone-1 (111, NC -HN-} H7-iso) 30 g (0.012 mol) 1 - ("- or. - The naphthyl) -2-bromopropanone-1 is dissolved in 150 ml of dry benzene and 24 ml (16.5 g, 0.03 mol) of isopropyl amine are added. The mixture is left for a day at 15-16 ° C. At a higher temperature, the reaction mixture is almost completely precipitated. The precipitate of the hydrobromide hydrochloride salt of Isopropylamine is filtered, washed twice with a small amount of dry benzene. The amount of hydrobromic salt is judged on the degree of reaction. The benzene is distilled off. The remaining oil is dissolved in 120 ml of dilute hydrochloric acid (1: 1), and the hydrochloric acid solution is left in the refrigerator for a day. The precipitate of the 1- (° C or p-n-Ltil) -2-isopropylaminopropylamine-1 hydrochloric acid salt is filtered off, the filtrate is evaporated to dryness, and the residue is added to the basic precipitate. All recrystallized from alcohol with ether. 1- (wasp or p-naphthyl) -2-diethylaminopropanone-1 (Oi, (C2Hj), This compound is obtained as the isopropylamino derivative described earlier. To 57 g (0.216 mol) 1 - "(-naphthyl) - 2-bromopropanone-1 in 300 ml of dry benzene was poured 57 ml (38.5 g, 0.525 mol) of diethyl jaja and left for three days at 15-1 bs, the reaction mixture was drained, as indicated earlier. 8 g of unreacted starting bromoketone are sour. The acidic solution is made alkaline to a strongly alkaline reaction with 40% sodium hydroxide solution, and the basement is extracted with benzene or chlorine. The extracts are dried with magnesium sulphate. The solvent is distilled off and the product is distilled in vacuum. 35 g (64%, calculated on bromoketone, 74%, calculated as reacted) are obtained, the Aminoketon quickly darkens and, therefore, immediately after distillation should be transferred to hydrochloric acid salt, which is usually prepared as follows: To the acetone solution of the amino ketone, an equivalent amount of a 10% acetone solution of hydrogen chloride is added while cooling. The mixture is left in the refrigerator for 2-3 hours. The precipitate of the acidic salt is filtered off, and dry ether is added to the filtrate to obtain some more salt. The total yield of hydrochloric acid salt is 90-95%. 1- (o: -or (-naphthyl)) -2-piperidinopropanone-1 (Ili, NRj-N H). The compound is prepared analogously to the indicated amino-derivatives, 4.2 g (0.016 mol) of bromoketone, 3.4 g (0.039 mol ) piperidine in 30 ml of dry benzene is left for two days at 16-18 ° C. The mixture is treated as before. The sulfate solution is boiled with coal, cooled and alkalinized, with cooling, to a strongly alkaline reaction with 40% sodium hydroxide solution. The precipitated yellowish precipitate is filtered and air dried. ,

1- (5,6,7 8-Tetrahydro-G-or 2-naphthyl) -2-alkylaminopropanol-1 (loi or I).

The reduction of amine ketone chlorohydrates is carried out under pressure in an autoclave at 60-70 atm and a temperature of 10 ° -11 °. Skeletal nickel is used as a catalyst, the solvent is an aqueous alcohol or other suitable solvent. Irodolite reduction of the activity of the catalyst (6-24 h). The progress of the reaction is judged by the amount of absorbed hydrogen as well as by the disappearance of the absorption band -CO- in the IR spectra.

After the reduction is complete, the catalyst is filtered off and the solvent is distilled off to dryness. The residue of the acid salt of amino alcohol is recrystallized from a suitable solvent (for example, from an alcohol with ether).

By alkalinizing hydrochloric aqueous solutions of amino alcohols, free bases can be isolated. The structure of amino alcohols proved IR, NMR spectroscopy and confirmed by elemental analysis.

Claims (1)

METHOD FOR PRODUCING 1- (5 ^ 60 (8 ^ TETRAHYDRO-1'- OR 2'-NAPHTHYL) -2ALKYLAMINOPROPANOLES-1, characterized in that naphthalene is reacted with Λ-bromopropionyl bromide in an organic solvent such as chloroform or nitroben According to the Friedel-Crafts reaction in the presence of aluminum chloride, the obtained 1 - (<X- or p-naphthyl) -2-brompro.panon-1 is reacted with the corresponding alkylamine in an inert solvent, for example benzene, and the resulting aminoketone is reduced catalytically to pressure autoclave, target product Uct is isolated in the form of salt.