NO142103B - EQUIPMENT FOR USE IN AND ON AGRICULTURAL PRODUCTS - Google Patents

Abstract

Fungicide for use in and on agricultural products.

Description

Process for the production of therapeutically valuable, basic substituted diphenylalkane derivatives.

The object of the invention is a method for producing basic substituted

diphenylalkane derivatives.

It has been found that basic substituted diphenylalkane derivatives of the general formula

wherein R means a halogen atom or a low molecular weight alkyl group, R, and R, means

hydrogen atoms, low molecular weight alkyl or

alkoxy groups or halogen atoms, and n

means the whole numbers 1 or 2, have valuable

therapeutic properties, especially cardiac and

cycle action, and that you get these compounds when you a) reduce phenylacetone

in the presence of amines with the general

formula II

in which R, R1, R2 and n have the above meaning, or that one reacts phenylacetone with amines of the general formula II, and then reduces the condensation product, or b) reacts an amine of formula II with l-phenyl-2-halopropane- respectively propene, optionally in the presence of hydrogen halide-releasing agents, and hydrates an optionally present double bond, or c) reacts 2-amino-3-phenylpropane with compounds of the general formula

in which R, Rp R2 and n have the above meaning, and Hal stands for chlorine, bromine or iodine, optionally in the presence of hydrogen halo-

genide-releasing agents, or

d) reduces aldehydes with the general formula

wherein R, R, and R;, have the above meaning and m stands for the numbers 0 or 1, in the presence of 2-amino-3-phenyl-propane, or reacts 2-amino-3-phenyl-propane with aldehydes of the formula IV and then reduces the condensation products or e) reduces carboxylic acid amides of the general formula in which R, R, R 2 and m have the above meaning, or f) hydrates compounds of the general formula VI

in which R, R, R, and m have the above meaning, in a manner known per se, and optionally transfer the basic compounds formed into the corresponding salts of inorganic or organic acids.

The reduction of phenylacetone in the presence of amines of the formula II is particularly advantageous for the production of the new process products. As amines can be used, for example: 1-phenyl-1-p-(m,o)-chlorophenyl-propylamine-(3),

l-phenyl-l-p-(m,o)-chlorophenyl-ethylamine-(2),

1,1-di-p (m,o)-chlorophenyl-propylamine-(3), l,l-di-p(m,o)-chlorophenyl-ethylamine-(2), l-p (m,o)- chlorophenyl-1-p(m,o)-methoxyphenyl-propylamine-(3),

l-p(m,o)-chlorophenyl-l-p(m,o)-methoxyphenyl-ethylamine-(2),1-p(m,o)-chlorophenyl-1-(3',4'-dichlorophenyl)-propylamine - (3), l-p (m,o)-chlorophenyl-1-(3',4'-dichlorophenyl)-ethylamine- (2), l-p (m,o)-chlorophenyl-1-(3'-methyl- 4'-chlorophenyl)-propylamine-(3), l-p (m(o)-chlorophenyl-1-(3'-methyl-4'-chlorophenyl)-ethylamine-(2), l-p(m,o)- chlorophenyl-1-(3'-methyl-2'-chlorophenyl)-propylamine-(3), l-p(m.o)-chlorophenyl-1-(3'-methyl-2'-chlorophenyl)-ethylamine-(2) ,

1-p(m,o)-tolyl-1-(3'-methyl-2'-chlorophenyl)-propylamine-(3),

1-p(m,o)-tolyl-1-(3'-methyl-2'-chlorophenyl)-ethylamine-(2), 1-p(m,o)-isopropyl-phenyl-1-(4'-chloro-3 '-methyl-phenyl)-propyl-amine-(3), 1-p(m,o)-isopropyl-phenyl-1-(4'-chloro-3'-methyl-phenyl)-ethylamine- (2), l-p(m,o)-tolyl-l-phenyl-propylamine- (3) ,-l-p-(m,o)-tolyl-l-phenyl-ethylamine-(2), l-p (m,o)-ethylphenyl-l-f enyl-propylamine-(3),

l-p(m,o)-ethylphenyl-l-phenyl-ethylamine-(2),

l-p (m,o)-isopropyl-phenyl-l-phenyl-propylamine-(3),

l-p (m,o)-isopropyl-phenyl-l-phenyl-ethylamine-(2),

1-p(m,o)-tolyl-1-(2'-chloro-5'-methylphenyl)-propylamine-(3),

1-p (m,o)-tolyl-1-(2'-chloro-5'-methyl-phenyl)-ethylamine-(2),

1-p(m.o)-methoxyphenyl-1-(2'-chloro-5'-methyl-phenyl)-propylamine-(3), 1-p(m,o)-methoxyphenyl-1-(2'-chloro-5'- methyl-phenyl)-ethylamine-(2), 1-p(m,o)-methoxyphenyl-1-phenyl-propylamine-(3) and l-p(m,o)-methoxyphenyl-l-phenyl-ethylamine-(2) .

These amines can be prepared according to known methods, for example by the action of aryl-magnesium halides on cinnamic nitriles and subsequent catalytic hydrogenation of the diphenyl-propionitriles formed. The diphenylethylamines are obtained by catalytic hydrogenation of the diphenylacetonitrile.

The reduction of phenylacetone in the presence of the amines can e.g. is carried out by means of catalytic hydrogenation. As catalysts, the metals from the 8th group of the periodic system, especially the noble metals, are suitable. Appropriately, one works in the presence of the solvents which are common for hydration purposes, e.g. aqueous alcohols, alcohols or water. Nickel catalysts can also be used, preferably Raney catalysts. The reduction can also be carried out with the aid of sodium borohydride, as it is appropriate to first prepare the condensation product of amine and phenylacetone, possibly at slightly elevated temperatures, as well as possibly in the presence of an indifferent organic solvent, for example benzene or toluene, and reduce by portionwise addition of sodium borohydride after dilution with a suitable solvent, for example low molecular weight alcohols, possibly in the presence of water. One can also reduce with nascent hydrogen, e.g. with aluminum amalgam and alcohol, sodium amalgam or lithium aluminum hydride. The reduction can also be carried out electrolytically.

According to a further advantageous embodiment of the method according to the invention, the above-mentioned amines of formula II can be reacted with 1-phenyl-2-halopropanes or propene.

As such l-phenyl-2-halo-propanes

respectively Propene can be used:

1-phenyl-2-chloro-propane, 1-phenyl-2-bromo-propane or 1-phenyl-2-iodo-propane, as well as the corresponding 1-phenyl-2-halo-propenes. The 1-phenyl-2-halopropanes can also be obtained by halogenation of methyl-benzylcarbinol (cf. Beilstein, volume 5, 391 and volume 5, 1st supplementary work 190).

This reaction is suitably carried out in suitable solvents, for example aromatic hydrocarbons such as benzene or toluene by prolonged heating. Advantageously, 1 mol of 1-phenyl-2-halopropane or -propene with 2 moles of the amine used for binding free hydrogen halide. The hydrogen-halide bond can also take place with the help of the usual basic agents, such as alkali and alkaline earth carbonates or hydroxides, as well as organic bases such as pyridine or quinoline, which can possibly simultaneously serve as a solvent. The work-up takes place in the usual way by separating the halohydrogen acid salt from the base used, for example by precipitation with ether or shaking out with water. The process product can be purified by distillation or by transfer in a suitable salt. If propene halides are used, the double bin is subsequently hydrogenated according to methods known per se.

A further possibility for the production of the process products consists in reacting compounds of the aforementioned formula III with 1-phenyl-2-aminopropane corresponding to the regulation stated above. As compounds of formula III, the compounds corresponding to the amine of formula II which contain a halogen atom instead of the amino group can be used. Examples include l-phenyl-p-(m,o)-chlorophenyl-3-chloropropane and l-phenyl-l-p(m,o)-chlorophenyl-2-chloroethane, which can be prepared in the usual way by halogenating the correspondingly substituted diphenylpropyl resp. diphenylethyl alcohols, sm. e.g. Bull. Soc. chim. France [5] 23, 936 (1956).

A further embodiment of the method according to the invention consists in reducing aldehydes of formula IV in the presence of 1-phenyl-2-aminopropane. As aldehydes, for example, p,(3-diphenyl-propionaldehyde and diphenyl-acetaldehyde can be used, the phenyl radicals can contain the specified substituents R — R2. These aldehydes can, for example, be obtained by heating correspondingly substituted a,a'-dihydroxybenzyls according to Recueil Trav. chim. Pays-Bas 21, 36 or according to U.S. Patent No. 2,446,522 of chloroacetaldehyde acetals and diphenylmethanes The reaction takes place preferably by hydrogenation The hydrogenation is suitably catalytic with the help of metals from the 8th group of the periodic table, preferably noble metals such as palladium or platinum, in the presence of common solvents for this purpose, e.g. aqueous alcohols, alcohols or water. Raney catalysts can also be used. Furthermore, one can also reduce with nascent hydrogen, e.g. aluminum amalgam and alcohol, sodium amalgam , lithium aluminum hydride or particularly advantageously with sodium borohydride. Furthermore, the reduction is also feasible electrolytically. In many cases it can be expedient to first isolate the condensation products obtained from aldehyde and l-phenyl-2-amino-propane, and then reduce in the second reaction step. The condensation carried out in the first step usually already takes place at room temperature or a slightly increased temperature (steam bath). It is appropriate to work in the presence of an indifferent organic solvent such as benzene or toluene. For the reduction, one advantageously uses one of the already mentioned solvents, and proceeds as indicated above. For example, you can reduce with sodium borohydride

According to a further embodiment of the method according to the invention, carboxylic acid amides with the general formula can also be reduced by methods known per se

wherein R, R, and R, have the said meaning | and m stands for the numbers O or 1, the reduction with lithium aluminum hydride being particularly suitable. The production of the carboxylic acid amides used as starting materials can, for example, be carried out by reacting acid chlorides with the general formula

wherein R, R,, R, and m have the aforementioned meaning with 1-phenyl-2-amino-propane. The

corresponding carboxylic acids can, for example, be obtained by adding aromatic hydrocarbons to cinnamic acid using aluminum chloride or concentrated sulfuric acid (cf. Chem. Ber. 56, 1131 and German patent no. 1,064,494).

The reduction of the carboxylic acid amides using lithium aluminum hydride is carried out according to methods known per se, suitably in the presence of indifferent solvents such as ether, dioxane or tetrahydrofuran. It is appropriate to work in such a way that the carbonic acid amide is added to the lithium aluminum hydride suspension in one of the aforementioned solvents, then the reaction mixture is allowed to boil under reflux for some time, and then carefully mixed with water and worked up in the usual way by separating the organic and the inorganic components. The reduction of the carboxylic acid amides to the corresponding amines can also be carried out electrolytically.

Finally, the process products can also be prepared in such a way that the compounds with the general formula are hydrogenated in a manner known per se

wherein R, R 1 , R 5 and m have the aforementioned meaning. The production of such unsaturated compounds can, for example, take place by dehydration of compounds with the general formula

Dehydration is usually successful by brief heating with acids, for example hydrohalic acids, sulfuric acid, phosphoric acid etc. 1. It can also be carried out with the help of phosphorus pentoxide, phosphorus halides and thionyl chloride. The transfer of the unsaturated compounds of the formula VI to the process products advantageously takes place by catalytic hydrogenation. Metals from the 8th group of the periodic system, such as palladium, platinum or nickel, are preferably used as catalysts. Raney catalysts can also be used.

The process products can be transferred as basic compounds by means of inorganic or organic acids in the corresponding salts. As inorganic acids can be used, for example: halogenated hydrogen acids such as hydrochloric acid and hydrobromic acid, as well as sulfuric acid, phosphoric acid and amidosulfonic acid. Examples of organic acids include: Formic acid, acetic acid, propionic acid, lactic acid, glycolic acid, gluconic acid, maleic acid, succinic acid, tartaric acid, benzoic acid, salicylic acid, citric acid, aceturic acid, oxyethanesulfonic acid and ethylenediaminetetraacetic acid. The process products have an over- properly beneficial cardiac and circulatory effects. Thus, e.g. administration of 1-phenyl-2-[1'-p-chlorophenyl-1'-(4"-chloro-3"-methylphenyl)-propyl-(3')]-aminopropane in experiments on isolated rabbit hearts according to Lan- gendorff by a single injection of only 2.5 y to a strong coronary dilation which, compared to the normal untreated heart, corresponds to an increase in the coronary flow of approx. 50 percent l-phenyl-2-[l', l'-diphenyl-propyl-(3') ]-amino-propane, which is known from Belgian patent 578,515, causes in anesthetized dogs after injection into the left coronary arteries ramus circumflexus in a dosage of 0.2 mg an average increase in coronary flow of 100 percent. Under the same conditions, l-phenyl-2-[l'-p-chlorophenyl-1'-(3"-methyl-4 "-chlorophenyl)-propyl(3')]-amino-propane at a dosage of 0.5 mg average 180 percent and 1-phenyl-2-[1'-p-chlorophenyl-1'-phenyl -propyl-(3')]-amino-propane in propylene glycol solution with an average of 175 per cent.

The process products are considerably superior to the already known compounds of similar structure. Thus, for example, of the already known 1-phenyl-2-[l',l'-diphenylpropyl-(3'y-amino-propane) the administration of the double dose (5 y) is necessary when an equally strong coronary dilation is to be achieved effect. The new process product's toxicity (Dos. let. min. i. v.) amounts to 10 mg per kg, with regard to the double coronary artery widening effect in relation to the mentioned known compounds is more favorable than the corresponding value of the said known compound, if Dos. let. min. i. v. in mice amounts to 15 mg/kg. A further significant advantage of the new method products in relation to the known compounds consists in that their coronary artery dilating effect lasts significantly longer in comparison. For example, the new method product l- phenyl-2-[1'-p-chlorophenyl-1'-(4"-chloro-3"-methyl-phenyl)-propyl-(3)]-aminopropane about 2 to 3 times longer coronary vessel dilating than the aforementioned known compound.

The process products can be applied parenterally or orally as such or in the form of their salts, possibly also in admixture with pharmaceutical usual carriers. In the case of oral application, tablets or dragees can preferably be used as the form of administration, for which the process products are processed as active substance with the usual carriers such as milk sugar, starch, tragacanth and magnesium stearate.

5-10 mg is administered as a single dose.

Example 1:

4.9 g of 1-p-chlorophenyl-1-phenyl-propylamine -(3) is heated with 2.7 g of phenylacetone for 30 min. in a steam bath. It is then diluted with 50 cm<3> of methanol and the reaction mixture is mixed in portions with 0.5 g of sodium borohydride. After a delay of 1 hour at approx. At 50° C, the solvent is distilled off under reduced pressure. 6 g of 1-phenyl-2-[1'-p-chlorophenyl-1'-phenylpropyl-(3')]-amino-propane are obtained in the form of an oil-like residue. After mixing with 2n-hydrochloric acid, the compound's hydrochloride crystallizes out, which after recrystallization from 70% ethanol melts at 146-147°C.

Example 2:

14 g of 1,1-di-p-chlorophenyl-propylamine-(3) are mixed with 6.7 g of phenylacetone and 30 cm<8 >toluene. After heating in a steam bath, the calculated amount of water separates. The mixture is diluted with 50 cm<:i> of methanol and 0.7 g of sodium borohydride is added in portions. After completion of the reaction, the solvents are evaporated under reduced pressure, the oil-like residue is taken up in ether. The ether solution is vigorously shaken with a solution of 5 g of glycolic acid in 100 cm<8> of water. Herein, l-phenyl-2-[ r-l'-di-p-chlorophenylpropyl-(3')]-amino-propaneglycolate is first secreted oil-like, but

hardens after a short time. The melting point is after recrystallization from ethanol/ether at 147° C.

Example 3:

Corresponding to the regulation stated in example 1, from 14 g of 1-p-chlorophenyl-1-p-methoxyphenyl-propyl-(3)-amine and 6.7 g of phenylacetone, 18 g of l-phenyl-2-[l'-p- chlorophenyl-1'-p-methoxyphenyl-propyl-(3')]-amino-propane. The maleate, which is obtained by adding a calculated amount of maleic acid in ethanol to an oil-like base, melts at 172-174°

C.

Example 4:

Corresponding to the regulation given in example 1, 16 g of l-phenyl-2-[l'-phenyl-1'-p-chlorophenyl-(2')]-amino-propane is obtained from 11.6 g of l-phenyl-l-p- chlorophenylethylamine-(2) and 6.7 g of phenylacetone. The maleate's melting point is 163-164° C (from ethanol).

Example 5:

Corresponding to the regulation given in example 1, 13.3 g of 1,1-di-p-chlorophenyl-ethylamine-(2) and 6.7 g of phenylacetone yield 18.5 g of l-phenyl-2[l\l'- di-p-chlorophenylethyl-(2')]-aminopropane. The maleate melts at 162-163° C (from ethanol).

Example 6:

Corresponding to the regulation given in example 1, 15.7 g of 1-p-chlorophenyl-1-(3',4'-dichlorophenyl)-propylamine-(3) and 6.7 g of phenylacetone yield 21 g of l-phenyl-2 -[1'-p-chlorophenyl-1'(3",4"-dichlorophenyl)-propyl-(3')]-amino-propane. The hydrochloride melts at 183-185° C (from ethanol).

Example 7:

Corresponding to the regulation stated in example 1, from 14.7 g of 1-p-chlorophenyl-1-(3'-methyl-4'-chlorophenyl-propylamine- (3) and 6.7 g of phenylacetone, 19 g of l-phenyl -2-[1'-p-chlorophenyl-1'-(3"-methyl-4"-chlorophenyl-propyl-(3')]-aminopropane. The corresponding hydrochloride melts at 185-186° C (from ethanol).

The easily water-soluble gluconate of this base can e.g. obtained in the following way:

2.7 g of the base are stirred with 1.3 g of gluconic acid lactone in 30 cm 8 of water at a bath temperature of approx. 60° C for several hours. After approx. After 10 hours, clear resolution has occurred. Ma adds 20 cm<:1> of water and obtains a 5% aqueous solution of the gluconate of the above-mentioned base.

Example 8:

Corresponding to the regulation given in example 1, 10.7 g of l-phenyl-1-(p-fluorophenyl)-ethylamine and 6.7 g of phenylacetone yield 14 g of l-phenyl-2-[l'-phenyl-2'- (p-fluorophenyl)-ethyl-(2')]-aminopropane, the maleinate of which after recrystallization melts at 157-159° C (from ethanol).

Example 9:

Corresponding to the regulation given in example 1, 13.2 g of 1-p-chlorophenyl-1-(p-fluorophenyl)-propylamine-(3) and 6.7 g of phenylacetone yield 17 g of 1-phenyl-2-[l' -p-chlorophenyl-1'-(p-fluorophenyl)-propyl-(3')]-amino-propane. The hydrochloride of the base melts at 201-203° C (from ethanol).

Example 10:

Corresponding to the regulation given in example 1, 10.6 g of 1-phenyl-l-p-tolyl-ethylamine-(2) and 6.7 g of phenylacetone yield 16 g of 1-phenyl-2-[l'-phenyl-l'- p-tolylethyl-(2')]-aminopropane. The maleate of the compound melts after recrystallization from ethanol at 168-169° C.

Example 11:

24.6 g of 1-chlorophenyl-1-phenyl-propylamine-(3) are boiled with 10 g of 1-phenyl-2-bromopropane in 150 cm<3> toluene for a few hours under reflux. After cooling, the toluene solution is shaken with water, dried and evaporated under reduced pressure. The oily residue (9 g) is mixed with 2n-hydrochloric acid, crystallizing the hydrochloride of 1-phenyl-2-[1'-p-chlorophenyl-1'-phenylpropyl-(3')]-aminopropane, m.p. . 146° C. (from dilute ethanol).

Example 12:

Corresponding to the regulation given in example 1, 17.5 g of 1-p-tolyl-1-(2-chloro-5-methyl-phenyl)-propylamine-(3) and 8.6 g phenylacetone 24 g l-phenyl-2-[l'-p-tolyl-l-(2"-chloro-5"-methylphenyl)-propyl-(3')]-aminopropane, whose maleate melts at 167-168 ° C (from vinegar).

Example 13:

20 g of y-phenyl-y-tolyl-propionic acid prepared according to the regulations stated in German patent no. 1,064,494 are heated with 40 cm 3 of thionyl chloride for 45 min. in a steam bath. After the reaction mixture has been evaporated under reduced pressure, the residue is taken up in 100 cm<3> ether and mixed until an alkaline reaction with 1-phenyl-2-aminopropane dissolved in the same amount of ether, since approx. 20 g of 1-phenyl-2-aminopropane. After 2 hours of stirring, the formed hydrochloride is suctioned off, the ether solution is washed with water, dried and evaporated. The oil-like brown residue dissolves in approx. 50 cm<3> of ether and added while stirring

a suspension of 5 g of lithium aluminum hydride in 200 cm<3> of ether. After boiling under reflux for 6 hours, the mixture is left overnight and then split with water. The formed precipitate is suctioned off and the ethereal solution is dried with sodium sulphate and evaporated. 5 g of 1-phenyl-2-[1'-p-tolyl-1'-phenyl-propyl-(3')]-amino-propane are obtained in the form of an oil-like residue. After addition of 2n-hydrochloric acid, an initially oil-like hydrochloride is obtained which crystallizes after addition of ether. After recrystallization from 70% ethanol, the hydrochloride melts at 171-173°C.

The same compound can also be prepared according to the regulations stated in example 1, reacting 4.5 g of 1-p-tolyl-1-phenyl-propylamine-(3) with 2.7 g of phenylacetone and then reducing with sodium borohydride . A sample of the hydrochloride of the base thus prepared gave no melting point depression with the process product prepared in the manner first described.

Example 14:

Corresponding to the regulation given in example 1, 12.7 g of 1-p-isopropyl-l-phenyl-3-amino-propane and 6.7 g of phenylacetone yield 18.4 g of l-phenyl-2-[l'-p -isopropyl-phenyl-1'-phenyl-propyl-(3')]-amino-propane in the form of an oil. The process product's maleinate melts after recrystallization from ethanol at 163-165°C.

Example 15:

Corresponding to the prescription given in example 1, 10 g of 1-p-isopropyl-phenyl-1-(3'-methyl-4'-chlorophenyl)-3-amino-

propane and 4.5 g phenylacetone 14 g 1-phenyl-2-[1'-p-isopropylphenyl-1'-(3"-methyl-4"-chlorophenyl)-propyl-(3')]-aminopropane in the form of an oil. The maleate melts at 177 to 179°C (from ethanol).

Example 16:

20 g of Y-pheny1-Y"(P"toly1)"Pr°Pionic acid prepared according to German patent no. 1,064,494 is reduced according to the regulation indicated in Bull. Soc. Chim. France [5] 20, 809 (1953)

by means of lithium aluminum hydride to 1-phenyl-l-(p-tolyl)-propanol-(3), then treated with phosphorus tribromide for 2 hours at 60° C, and thereby transferred into 1-phenyl-l-(p- tolyl)-3-bromo-propane. After adding ice water to the reaction mixture, the bromide is taken up in benzene and the benzene solution is mixed after drying using sodium sulphate with 1-phenyl-2-amino-propane.

After approx. After 6 to 8 hours of reflux, the corresponding 1-phenyl-2-[1'-(p-tolyl)-1'-phenyl-propyl-(3')]-aminopropane is obtained in the usual way as an oil. The base's hydro-

chloride melts at 172° C from 70 percent ethanol.

Example 17:

21 g tolyl-phenyl-acetaldehyde (prepared according to Compt. Rend. hebd. Seances Acad.

Pollock. 184, 1467) and 13.5 g of 1-phenyl-2-amino-propane are dissolved in 40 cm<3> toluene and heated

mes for Yi hour In a steam bath. After adding 80 cm8 of methanol, mix in portions with sodium borohydride. After the end of the reaction, the solvent is evaporated

where reduced pressure. The oil-like residue

duum is recorded in ether. After the addition of an equivalent amount of maleic acid, the maleate of 1-phenyl-2-[1'-phenyl-1-(p-tolyl)-ethyl-(2')]-aminopropane is obtained, which melts at 168°

C (from ethanol).

Example 18: 1-phenyl-2-[1'-phenyl-1'-p-tolylpropene-(1')-yl(3')]-amino-propane, which was pre-

prepared by water elimination from 1-phenyl-2-[ 1 '-phenyl-1'-p-tolyl-1'-hydroxypropyl -

(3') ]-aminopropane with the aid of toluenesulfonic acid in toluene, is hydrogenated in the presence of palladium catalysts. After filtration and evaporation of the filtrate, 1-phenyl-2-[1'-phenyl-1'-p-tolylpropyl-(3')]-amino-

propane as oil. The base hydrochloride melts

ter at 170-171° C.

The necessary starting material 1-phenyl-2-[1'-phenyl-1'-p-tolyl-1'-hydroxypropyl-(3')]-aminopropane can be prepared in the following way: Phenyl-p-tolyl ketone (Beilstein 7, 440) is condensed with acetonitrile in the manner indicated in Liebig's Ann. Chem. 603, 189

(1957). The thus formed (3-phenyl-p-p-tolyl-p-hydroxy-propionitrile is hydrogenated with the aid of Raney nickel in ammonia-

calc methanol. The 1-phenyl-1-p-tolyl-1-hydroxy-propyl-(3)-

amine is condensed with phenylacetone according to the regulations given in example 1, and redu-

is then converted using sodium borohydride to 1-phenyl-2-[1'-phenyl-1'-p-tolyl-1'-hydroxy-propyl(3')]-aminopropane.

Claims (1)

Process for the preparation of therapeutically valuable, basic substituted diphenylalkane derivatives of the general formula in which R means a halogen atom or a low-molecular alkyl group, R, and R2 means hydrogen atoms, low-molecular alkyl or alkoxy groups or halogen atoms, and n means the numbers 1 or 2, as well as acid addition- salts of these compounds, characterized in that one a) reduces phenylacetone in the presence of amines of the general formula in which R, R, and R2 and n have the above meaning, or that one reacts phenylacetone with amines of the general formula II and then reduces the condensation product, or b) reacts an amine of formula II with l-phenyl- 2-halopropane or -propene optionally in the presence of hydrogen halide-releasing agents, and hydrates an even tually present double bond, or c) reacts 2-amino-3-phenyl-propane with compounds of the general formula in which R, R,, R., and n have the above meaning, and Hal stands for chlorine, bromine or iodine, possibly in the presence of hydrogen-halide removing agents, or d) reduces aldehydes of formula wherein R, R, and R2 have the above meaning and m represents the numbers 0 or 1, in the presence of 2-amino-3-phenyl-propane, or reacts 2-amino-3-phenyl-propane with al dehydrogenates of formula IV and then reduces the condensation products, or e) reduces carboxylic acid amides of the general formula in which R, R1, R2 and m have the above-mentioned meaning or f) in a manner known per se hydrates compounds of the general formula in which R, R1, R2 and m have the above-mentioned meaning, and optionally transfer the formed basic compounds to the corresponding salts of inorganic or organic acids.