SU497766A3 - Method for producing amino derivatives of 1,2-diphenyl-1,1,2.2-tetrafluoroethane - Google Patents

Description

(54) METHOD FOR OBTAINING 1,2-DIPHENYL-1,1,2,2, -TETRAFTORETHANE AMINO DERIVATIVES

The invention relates to new, not described in the literature, substituted benzylamine with high physiological activity, which can be used in medicine. A known method for producing amino derivatives of 1,2-diphenyl-1,1,2,2-tetrafluoroethane of the general formula: CF, - CF, W where XF, C1, Br, J, OA1K, OAg, NO, NH2NHA1K n NHAr, consisting of that 1,2-diphenyl-1,1,2,2-tetrafluoroethane or its derivatives are nitrated with nitric acid or a mixture of nitric and sulfuric acids, and the resulting nitro compounds are treated with a reducing agent, for example a solution of tin dichloride in concentrated hydrochloric acid. However, there is no information in the literature on the preparation of amino derivatives of 1,2-diphenl1, 1,2,2-tetrafluoroethane of the general formula A, where X is a group. where R and RI each represent hydrogen or lower alkyl having valuable properties. A method for the preparation of amino derivatives of 1,2-difleinyl-1,1,2,2-tetrafluoroethane of the general formula A is proposed, which consists in that the substituted 1,2-diphenyl-1,1,2,2-tetrachloroethane is reacted with metal fluoride, for example, with mercury fluoride, in anhydrous hydrogen fluoride, followed by separation of the target product in a known manner. Example 1. 4- (2-phenyl-G, 1,2,2-Tetrafluoroethyl) -. A, a-dimethylbenzylamine. A. 1-Chloro-1-paracumylethylene. 4-Isopropyl acetophenone 1.2 g (0.1 mol) is gradually added to a cooled and vigorously stirred suspension of 208 g (1.0 mol) of ethyl chloride phosphorus in 1500 ml of hexane. After the termination of the release of hydrogen chloride, the reaction mixture is slowly poured into a stirred mixture (2 kg) of ice and water. The organic layer is separated, washed thrice with water, then with sodium bicarbonate solution until neuralization and again with water. The hexane solution was dried over anhydrous magnesium sulphate; hexane was distilled off under reduced pressure and under fractional distillation at a pressure of 1 mm Hg. Art. Get pure 1-chloro-1-cumylethylene.

B. Para- (1-vinyl chloride) -a, a-dimethylbenzylamine. 1-Chloro-1-paracumylethyl 90.3 g (0.5 mol) was charged into a 1 L three-neck flask equipped with a stirrer, an addition funnel and a thermometer, and 20 ml of anhydrous methylene chloride was added. The flask is placed in a cooling bath and its contents are stirred until the temperature drops to 0 ° C. Then, 13.3 g (0.10 mol) of anhydrous aluminum chloride and 2 g (0.015 mol) of r / jer-butyl bromide are added. A solution of three-chlorine nitrogen (0.5 mol in approximately 150 ml of methylene chloride) is loaded through the funnel into the depth of the stirred mixture for 45-60 minutes. After completion of the reaction, the mixture is poured into ice-cold water with stirring, and the whole mass is strongly alkalinized with sodium hydroxide. The methylene chloride layer is separated and the aqueous phase is extracted twice with 100 ml of ethylene chloride. The extract is treated with shaking 100 ml of 2.5 n. hydrochloric acid. Unreacted 1-chloro-1-pacumylethylene is removed from the solvent phase by fractionated distillation; the aqueous phase is again strongly basified and the amine is isolated by extraction and vacuum distillation. The procedure is repeated until a sufficient amount of product is obtained.

B. 4-Ethynyl-: a, a-dimethylbenzylamine. The product obtained in Step B 19.6 g (0.1 mol) is added to a solution of 8 g (0.14 mol) of potassium hydroxide in 100 ml of absolute ethanol and heated under reflux for 24 hours. Then the reaction mixture was poured into ice water and the organic product was extracted with benzene. The extract is washed with 2.5 n. hydrochloric acid, water, and dried over sodium sulfate. Pure acetylene is obtained by distillation under reduced pressure.

G. 4-Ethynyl - a, a-dimethylbenzylamine-copper. A solution of copper dinamide is prepared by passing ammonia through a deaerated suspension of 9.5 g (0.05 mol) of copper iodide in water. The product of stage B is dissolved in 100 ml of tetrahydrofuran and 8.0 g (0.05 mol) are added and the copper complex is added with stirring; the yellow precipitate formed 4-ethinyl-a, a-dimethylbenzylamine — copper is filtered and dried in a stream of nitrogen at 50 ° C.

D. 4- (a-aminisopropyl) tolan. The product of step D 8.9 g (0.04 mol) is added to a solution of 8.2 g (0.04 mol) iodobenzene in 100 ml of anhydrous pyridine. The mixture is heated under reflux in an atmosphere of anhydrous nitrogen for 10 hours, and then poured into 300 ml of water. Pyridine is distilled as azeotropic

mixtures with water and the residue in the flask are extracted with enough chloroform containing acetic acid to destroy the copper-amine complex of the blue color. After coal bleaching and

by recrystallization from methanol in the presence of sodium hydroxide in an amount sufficient to neutralize, pure 4- (a-aminiminonpropyl) tolane is obtained.

E. (2-Phenyl-1,1,2,2-tetrachloroethyl) -a, a-dimethylbenzylamine hydrochloride. The product of the stage D 7.06 g (0.3 mol) is dissolved in 50 ml of chloroform, cooled to 0 ° C. Hydrogen chloride is passed through the solution in excess. Then the temperature is lowered to -20 ° C and

anhydrous chlorine in excess is passed through the solution. This excess is removed with a stream of nitrogen. By removing chloroform under reduced pressure, a waxy product is obtained, which is transferred to a polyethylene

flask using fresh anhydrous tetra. chloroethylene.

G. 4- (2-phenyl-1, 1, 2,2-tetra afore-ethyl) -e, a-dimethylbenzylamine. The product of stage E is treated with 7.5 g of mercury oxide (excess) and,

keeping the temperature in the range from 15 to 20 ° C, the mixture is stirred for 16 hours, anhydrous hydrogen chloride is passed through it. The mixture is poured into water, made alkaline with sodium hydroxide.

and the precipitate formed is filtered, dried and extracted with benzene. After recrystallization, pure 4- (1, 1,2,2-tetrafluoroethyl) -a, a-dimethylbenzamine is obtained.

Example 2. 4- (2-phenyl -, 2,2-tetraftoethyl) -a, “- dimethylbenzylamine.

A. M-Trifluoroacetyl-, a, a - dimethylbenzylamine. a, a-Dimethylbenzene, 67.6 g (0.5 mol) was dissolved in 200 ml of anhydrous benzene and 89.1 g (0.5 mol) of trifluoroacetic anhydride was added dropwise with cooling. After elimination of heat release, the mixture is cooled on ice, the benzene layer is washed with sodium bicarbonate solution and

water, dried and evaporated to form crystals.

B. 4-Nitro-Y-trifluoroacetyl-a, a-dimethylbenzylamine. The product of stage A, 92.4 g (0.4 mol) is gradually added to 340 g

(5 mol) of fuming nitric acid at -20 ° C and vigorous stirring. After all the acetylated amine has been added, the mixture is stirred for another 30 minutes, and then poured into ice-water, basified with ammonia solution. The crystalline precipitate is recrystallized from aqueous ethanol.

B. 4-Amine N-trifluoroacetyl-1a, a-dimethylbenzylamine. The product of stage B, 82.9 g (0.3 mol), is dissolved in 1 l of 50% aqueous diglyme and, with stirring, 800 g of sodium hydrosulfite are added to the solution. After bleaching, the mixture is re-extracted with benzene. The benzene extract is washed with water, and then 2.5 n. hydrochloric acid (about 200 ml); The 4-amino derivative is precipitated with sodium bicarbonate and recrystallized from ethanol.

G. 4-Iodine-M-trifluoroacetyl-a, a-dimethylbenzylamine. The product of stage B is 14.2 g (0.2 mol) dissolved in 100 ml of concentrated hydrochloric acid, 200 g of ice and 100 ml of water. After the temperature was reduced to 5 ° C, a solution of 14.5 g (excess) of sodium nitrite was added dropwise with stirring. When an excess of nitrous acid is formed, the addition of nitrite is stopped, the ayut is dissolved, and the excess is decomposed by sulfamic acid. Then, with stirring, a solution containing 23.3 g (a slight excess) of potassium iodide is added and the mixture is kept at room temperature overnight. The resulting suspension is then mixed with 300 ml of benzene, the benzene layer is separated, washed with water, dried, decolorized with charcoal and concentrated to crystallization; get pure 4-iodine-Y - trifluoroacetyl-a, and - dimethylbenzylamine.

D. 4-iodine-a, a-dimethylbenzylamine. The product of stage D 35.7 g (0.1 mol) is dissolved in 200 ml of ethanol and treated with a solution of 20 g of sodium carbonate in 100 ml of water. The resulting suspension is heated on a steam bath with stirring until a sample is completely soluble in dilute hydrochloric acid. The pH is then adjusted to about 14 and the suspension is distilled with steam under a nitrogen atmosphere. Upon extraction of the oily distillate with benzene and repeated distillation under reduced pressure, pure 4-iodo, a, a-dimethylbenzylamine is obtained.

E. 4- (a-Aminoisopropyl) Tolan. Copper phenylacetylide 11.22 g (0.08 mol), prepared as described in example 1 (step D), is added to 20.9 g (0.08 mol) of 4-iodo-a, adimethylbenzylamine in pyridine, as in example 1 (stage D).

J. Hydrochloride- (2-phenyl-1,1,2,2-tehrahloroethyl) -a, a-dimethylbenznlamin. The product of stage E 7.06 g (0.03 mol) is dissolved in 50 ml of chloroform, cooled to 0 ° C and anhydrous hydrogen chloride in excess is passed through the solution. The temperature is then lowered to and anhydrous chlorine is passed in excess, which is removed by a stream of nitrogen. Chloroform is then removed under reduced pressure and the waxy product is transferred to a polyethylene flask using freshly distilled anhydrous tetrachloroethylene.

3. 4- (2-phenyl-G, G, 2,2-tetrafluoroethyl) -a, adimethylbenzylamine. The product of stage W is treated with 7.5 g (excess) of mercury oxide and, maintaining the temperature from 15 to 20 ° C, the mixture is stirred, anhydrous hydrogen fluoride passes through it, for 16 hours. After that, the mixture is poured into water,

alkaline with sodium hydroxide and the precipitate formed is filtered, dried and extracted with benzene. After recrystallization, pure 4- (2phenyl-G, G, 2,2-tetrafluoroethyl) -a, .a - dimethylbenzylamine is obtained.

Invention

The method of producing amino derivatives of 1,2 diphenyl-1, 1,2,2-tetrafluoroethane of the general formula

CF,

where X represents a group

-C (CH5) 2 6 H-position

F

R (to

wherein R and RI each represents hydrogen or lower alkyl, characterized in that the substituted 1,2-diphenyl-1,1,2,2-tetrachloroethane is reacted with metal fluoride, for example, mercury fluoride, in anhydrous hydrogen fluoride, followed by separation target product in a known manner.