SU439963A1 - Method for preparing phenylaminoalkanes - Google Patents

Description

Tyor 1- (4-chloro-3-trifluoromethylphenyl) -2-nitropropane in 100 ml of ether and the mixture is refluxed for 2 hours. Then it is poured into ice water, the ether phase is dried, evaporated and subjected to fractional distillation. From 1-4- (chloro-3-trifluoromethylphenyl) -2-aminopropane (T. Il., Boiling point is 124 ° C) in acetonitrile and hydrochloric acid in ether, the hydrochloride is obtained, which is recrystallized from a small amount of acetonitrile and melts at 196 -198 ° C.

In a similar manner, 1- (6-chloro-3-trifluoromethylphenyl) -2-aminopropane-hydrochloride is obtained, mp. 226-230 ° C.

Example 2. 4-chloro-3-trifluoromethyl-a-methylphenethylcarbamic acid ethyl ester.

To a mixture of 7 g of 1- (4-chloro-3-trifluoromethylphenyl) -2-aminopropane obtained by the method of Example I, 4 g of sodium carbonate and 50 ml of acetonitrile are added dropwise 3.3 g of ethyl chloroformate and for 15 min, heated to 40 ° C. Then stirred for 12 hours, sucked off and evaporated. The remaining oil is dissolved in ether, shaken with -c dilute hydrochloric acid, the ether phase is evaporated. After fractional distillation, 4-chloro-3-trifluoromethyl-a-methylphenethylcarbaminoBoBic acid ethyl ester (m.p. b.o. 135-140 ° C) is obtained, which is recrystallized from petroleum ether, m.p. 56-58 ° C.

Similarly, (4-chloro-3-trifluoromethylphenyl) -2propyl-thiol-carbamic acid ethyl ester is obtained, m.p. 67 ° C.

Example 3. 1- (4-chloro-3-trifluoromethylphenyl) - (7-thiofillinyl) -ethylamino-propane.

A mixture consisting of 15 g of I- (4-chloro-3-trifluoromethylphenyl) -2-aminopropa and 7.6 g of 6- (2chloroethyl) -thiofillin is heated to 190 ° C. When this happens, an exothermic reaction occurs. Then it is stirred at 170 ° C for 1 hour, cooled, acetic ether is added, the filtrate is sucked off and the filtrate is acidified with hydrochloric acid in ether.

The resulting 1 - (4-chloro-3-trif hormethylphenyl) - {7-thiofillinyl) - ethylamino-propane-hydrochloride, after recrystallization from methanol, has an mp. 244-248 ° C.

Example 4. 1 - (4-chloro-3-trifluoromethylphenyl) -2-acetonylamino) propane.

To a boiling mixture consisting of 6.45 g of 1- (4 chloro-3-trifluoromethylphenyl) -2-aminopropane, 50 ml of acetonitrile and 2.93 g of sodium carbonate are added dropwise 2.53 ml of chloroacetone and over a period of 1 hour boil under reflux. After suction and evaporation, the residue is dissolved in ethyl acetate and hydrochloric acid in ether and ether is precipitated with 1- (4 chloro-3-trifluoromethylphenyl) -2 - (acetonylamino) propane-hydrochloride, which after recrystallization from isopropanol melts at 191 -194 ° WITH.

Example 5. 1- (4-chloro-3-trifluoromethylphenyl) -2- (2-cyanoethylamino) -prop n.

A mixture consisting of 5 g of 1- (4-chloro-3-trifluoromethylphenyl) -2-aminopropane and 1.2 acrylonitrile is stirred at 90 ° C for 5 hours, then the unreacted still amine is distilled off (v. 15) 124 ° C) and 1- (4-chloro-3 trifluoromethylphenyl) -2- (2-cyanoethylamino) propane-hydrochloride is precipitated from the residue dissolved in acetic ester of the residue with hydrochloric acid in ether and ether, which after recrystallization from a small amount of water melts at 170 -173 ° C.

Example 6. 1 - (4-chloro-3-trifluoromethylphenyl) -2- (2-hydroxyethylamino) propane.

A mixture consisting of 23.7 g of 1- (4-chloro-3-trifluoromethylphenyl) -2-aminopropane, 3.6 g of ethylene oxide, 120 ml of methanol and 1.25 ml of water, in a pressure apparatus, two days shake at room temperature. After distilling off the solvent, the residue is subjected to fractional distillation. The resulting 1- (4-chloro-3-trifluoromethylphenyl) 2- (2-hydroxyethylamino) propane (m.p. b.o, 2-140-145 ° C) in ethyl acetate in hydrochloric acid in ether and ether are converted into the hydrochloride t. pl. 127-128 ° C.

Example 7. 1- (4-chloro-3-trifluoromethylphenyl) -2- (phenacylamino) propane.

A mixture consisting of 23.8 g of 1- (4-chloro-3-trifluoromethylphenyl) -2-aminopropane, 9.3 g of abroacetophenone and 100 ml of acetonitrile is stirred for 30 minutes and evaporated. After the addition of ether, it is filtered off with suction and the filtrate is evaporated. From the residue dissolved in acetonitrile, 1- (4-chloro-3-trifluoromethylphenyl) -2- (phenacylamino) propane-chlorohydride is isolated in ether with ether, which is recrystallized from methanol-water melts at 210-213 ° C.

Similarly to the method described in examples 3-7, receive:

1- (4-chloro-3-trifluoromethylphenyl) -2 - (2-hydroxyethylamino) -propanchlorohydrate, m.p. 127-128 ° C;

N- (4-chloro-3-trifluoromethyl-a-methylphenethyl) glycine ethyl ester hydrochloride, mp 165-167 ° C;

1- (4-chloro-3-trifluoromethylphenyl) -2- (3-hydroxypropylamino) propanchlorohydrate, m.p. 141 - 143 ° C;

1- (4-chloro-3 - trifluoromethylphenyl) - benzylaminopropane methanesulfonate, t. Pl. 158-162 ° C;

1- (4-chloro-3-trifluoromethylphenyl) - 2-ethylaminopropane-hydrochloride, so pl. 199-200 ° C;

N- (4 - chloro-3-trifluoro.methyl - a - methylphenethyl) -gly; cy - hydrochloride, so pl. 208-210 ° C (decomposition);

1- (6-chloro-3 - trifluoromethylphenyl) - 2-methylaminopropane-hydrochloride, so pl. 146-148 ° C;

1- (4-chloro-3 - trifluoromethylphenyl) -2-methylaminopropane-hydrochloride, t. Nl. .

Example 8. 2- (4-chloro-3-trifluoromethyl-amethylphenethylamino) -acetonitrile.

To 13.7 g of a 38% aqueous solution of sodium hydrosulfite is added 5 g of a 30% aqueous solution of formalin and stirred for 10 minutes. Then, 12 g of 1- (4-chloro-3-trifluoromethylphenyl) -2-aminopropane, prepared according to the procedure described for Example 1, is added dropwise to the mixture, and the temperature of the mixture rises to 60 ° C. After adding 3.75 g of potassium cyanide solution in 7.5 ml of water, stir for another 1 hour, then add water and extract with ether. The ether phase is dried and evaporated, and the remaining, oil is subjected to fractional distillation, which at 0.02 mm Hg. Art. and 130-150 ° C is converted to 2- (4-chloro-3-trifluoromethylphenethylamino) acetonitrile, dissolved in a small amount of ethyl acetate, acidified with methanesulfonic acid, and the methanesulfonate obtained after the addition of ether is recrystallized from alcohol, m.p. 181 ° С (decomposition).

Example 9. 1 - (4-chloro-3-trifluoromethylphenyl) -2- (3-chloropropylamino) propane.

3 g of 1- (4-chloro-3-trifluoromethylphenyl) -2- (3-hydroxypropylamino) propane-hydrochloride in 50 ml of acetonitrile with 1 ml of thionyl chloride is boiled under reflux for 30 minutes, the reaction mixture is evaporated, and the residue suspended in ether. Crystalline 1- (4chloro-3-trifluoromethylphenyl) -2- (3-chloropropylamino) -propane-hydrochloride is sucked off, after recrystallization from water, t. square 150-152 ° C.

In a corresponding way, they are obtained from 1 (4-chloro-3-trifluoromethylphenyl) -2- (2-hydroxyethylamino) propane with thionyl chloride 1- (4chloro-3-trifluoromethylphenyl) -2- (2-chloroethylamino-propane-hydrochloride, m.p. 154- G56 ° C.

Example 10. 1- (4-chloro-3-trifluoromethylphenyl) -2- (2-chloroacetylaminopropane).

A mixture of 62.8 g (0.2 mol) of 1- (4-chloro-3-trifluoromethylphenyl) -2-aminopropane and 10.2 ml of 2chloroacetyl chloride in 250 ml of acetonitrile is reacted for 1 hour at room temperature. Then the salt precipitated is filtered off, the filtrate is concentrated and the above compound is precipitated with petroleum ether, mp. 59-63 ° C.

Example 11. 1- (4-chloro-3-trifluoromethylphenyl) -2- (2-bepsylamino-acetylamino) propane.

12.6 g of 1- (4-chloro-3-trifluoromethylphenyl) -2 (2-chloro-acetylamino) -propane, prepared according to the procedure described in Example 10, by reacting 1- (4-chloro-3-trifluoromethylphenyl) -2-aminolpropa with chloroacetyl chloride in acetonitrile at room temperature, refluxed in 100 ml of acetonitrile with 9.4 g of benzylamine for 2 hours and after removal of benzylaminohydrochloride and the solvent is washed in acetic ether with water and osal {give hydrochloric acid in ether 1 - (4-chloro-3-trifluoromethylphenyl) -2- (2-benzylamino-acetylamino) -propane-hydrochloride, which is after recrystallization from water, it melts at 161 - 164 ° C.

Example 12. 1- (4-chloro-3-trifluoromethylphenyl) -2- (2-amino-acetylamino) propane.

By reacting 1- (4-chloro-3-trifluoromethylphenyl) -2- (2-chloro-acetylamino) -propane in dimethylformamide with phthalimid potassium at 100 ° C, 1- (4-chloro-3-trifluoromethyl-phenyl) -2- (2-phthalimidoacetylamino ) - propane.

6 g of this compound in 250 ml of ethanol are heated under reflux for 3 hours with 3.8 g of hydrazine hydrate, then acidified with ethyl acetate, cooled, sucked off and evaporated. The residue is dissolved in water, sucked off over active carbon, made basic, added ammonia, extracted with ethyl acetate, washed with water, dried and evaporated. The residue is dissolved in acetonitrile and acidified with methanesulfonic acid. The 1- (4-Chloro-3 trifluoromethylphenyl) -2- (2-amino-acetylamino) propane methanesulfonate crystallizes out, after recrystallization from alcohol, it melts at.

Example 13. 1- (4-chloro-3-trifluoromethylphenyl) -2- (2-hydroxy-2-phenylethylamino) propane.

The base, obtained from 7 g of 1- (4-chloro-3 trifluoromethylphenyl) -2 - (phenacylamino) propane-hydrochloride, at room temperature

0.7 g of sodium borohydride is reduced in 50 ml of ethanol, and after removing the solvent and decomposing the excess sodium borohydride in ether, the calculated amount of hydrochloric acid in ether is added. 1- (4-Chloro-3-trifluoromethylphenyl) -2- (2-hydroxy-2-phenylethylamino) propane-hydrochloride crystallizes out. After recrystallization from a small amount of acetonitrile, it melts at 165-167 ° C.

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Subject invention

The method of obtaining phenylaminoalkanes of General formula I

FjCR, CH,

// I

 CH-CH-NHR,

C1

where C1 is in the fourth or sixth position; RI is hydrogen or methyl; R2 is hydrogen, lower alkyl, benzyl, thiofillin- (7) -ethyl group, or groups, -СНСНСп-И, where or 2, Кз is carboxyl, alkoxycarbonyl, aminocarbonyl

or nitrile; -CmH2mR4 or CmH2m-l -

Sbpo-R4, where m is 2, 3, or 4, R4 is halogen, ox, ammonium or acylamino; -SiNi COR, where n is 1 or 2, R is lower alkyl or

phenyl; -CO-Rs, where Rs is a lower alkoxy, alkylthio, or benzyloxy group, or an alkyl which may be substituted with a halogen, hydroxy, or amino group, or their salts, characterized in that the nitrolefin of the total

Formula II

sn.

where R is as defined above, is reduced in a known manner, for example, lithium aluminum hydride, the compounds of general formula I obtained therewith are isolated or translated, and R2 is hydrogen, into compounds of general formula I, where Ra has the above values for Ra,

in a known manner, 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 antinode.