SU382278A1 - METHOD FOR OBTAINING AMINO ACIDS OR THEIR DERIVATIVES - Google Patents

Description

one

The invention relates to a method for producing new amino acid derivatives that can be used in the synthesis of physiologically active compounds.

The method of preparing "new compounds" is based on the known phenol C condensation reaction with functional substituted carboxylic acids in the presence of Friedel Crafts catalysts. However, in the invention using this reaction, new compounds not described in the literature have been obtained that can be applied in the synthesis of pharmaceutical preparations.

According to the invention, a method for preparing the compound- | and the general formula I is proposed.

(yogi.

where R, is hydrogen, hydroxy or lower alkoxygroup, lower alkyl, ga.choid or amino group; 11 is an integer from 1 to 3; Ra is hydrogen or lower alkyl; Ra -OXY-, lower alkoxy-, monoyl dnsubstituted lower; lilac agcinogroup; RI is hydrogen, lower alkyl, lower

alkaioyl or aroyl; RG is hydrogen or lower alkyl; RC and R - one of the residues of the hydroxy group, and

the other is lower alkanoyl. The method consists in the interaction of a compound of the general formula I and the preferred reader in the form of an L or DL form,

(Ri)

/

 CH-C-SOKS,

 /- four

R7

 Rb

where one of the | Restatts is R or R is hydrogen, and the other is Oxygroup, and all other designations correspond to the above, with a functional derivative of a lower carboxylic acid, for example, an acid halide, in the presence of a Friedel Crafts catalyst, followed by hydrolysis if necessary and the isolation of the target product by known method in free form or in salt form. If necessary, the resulting racemate is divided into optically active forms by one of the known methods.

A strong Lewis acid may be used as a Friedel-Crafts catalyst. The reaction should be carried out in the presence of solvent inert to Friedel Crafts reagents, for example, nitrobenzene, chlorobenzene, carbon disulfide and others. Anhydrides and acid halides can be used as a functional derivative of a lower carboxylic acid. The reaction is expediently carried out at O-200 ° C.

flip and measure 1. To a solution of 21.2 g of aluminum chloride in 80 ml of nitrobenzene, 7.24 g of β-rosin is added at room temperature, which dissolves with stirring after a few hours. Upon addition of 3.45 ml of acetyl chloride, the initial mixture is heated to 100 ° C for 6 hours, and the solution gradually becomes viscous and then solidifies. After cooling to room temperature, the solidified mass is added to 40 ml of concentrated hydrochloric acid and 200 g of ice. The aqueous phase is extracted with three portions of ethyl acetate, 200 ml each, after which the remaining clear aqueous solution is concentrated to a volume of 50 ml. After settling at 0 ° C, the reaction product, which is isolated in the form of crystals, is filtered off under suction, and the crude product is recrystallized from a small amount of semi-concentrated hydrochloric acid. After drying over potassium hydroxide and phosphorus pentoxide, the yield of 3-acetyl-L-tyrosine hydrochloride is 7.2 g (69% by weight), the decomposition point is 227-228 ° C, ag -3.2 ° (in water).

Example 2. Analogously to Example 1, starting from L-tyrosine, 3-Propionyl-L-tyrosine chlorohydrate is obtained with m. 223-225 ° C;

. 25

-1.3 ° (enter).

Example 3. To 110 ml of nitrobenzene, 26 g of anhydrous aluminum chloride, 7.9 g of acetyl chloride and 11.3 g of L-acetyl-L-tyrosine are sequentially added. After approximately 10 minutes, the additives are dissolved. Then the solution is heated to 100 ° C for 5 hours. The viscous, dark brown reaction mixture is cooled to 20 ° C and decomposed with a mixture of 250 g of ice and 25 ml of concentrated hydrochloric acid. 60 g of sodium chloride are added and the mixture is extracted with two portions of ethyl acetate, 500 ml each. The organic extracts are washed twice with a saturated solution of 100 ml each of salt and then extracted 3 times with 2 soda solution of 50 ml. The soda drains are brought to pH-1 with concentrated hydrochloric acid. The acidified solution is freed from vacuum from residual organic solvents and then cooled to 4 ° C for 14 hours.

Selected crystals are filtered and recrystallized from water with the addition of active carbon. Obtain 7.1 g (52 wt.%) N-3-diacetyl-L-tyrosine with T. pl. 142-143 ° C, 0.20,22,4 ° (in acetone).

Example 4. The process is carried out analogously to example 1, but with a reaction time of 20 hours, a starting point is 5-chloro-L-tyrosine, 3-acetyl-5-chloro-b-tyrosine hydrochloride with m.p. 231 ° C (with decomposition).

11 p and m p 5. 35.35 g of aluminum chloride in powder form is dissolved at room temperature in 133.5 ml of nitrobenzene. Then 12 g of 1-tyrosine and 5.75 ml of acetyl chloride are added. The mixture is heated for 6 hours to

after cooling, it is added to 66.5 ml of concentrated hydrochloric acid and 335 ml of ice-cold water. The aqueous phase is separated, washed with three portions of ethyl acetate, 350 ml each, concentrated to 100 ml and cooled, and the crystallized reaction product is filtered off. After double non-recrystallization from 5 n. hydrochloric acid gives 7.7 g of 4-acetyl-OH-L-throsine hydrochloride with m.p. 217-220 ° C.

Example 6. To a suspension of 33.9 g of Z-dimethyl DL-tyrosine in 340 ml of nitrobenzene, 71.3 g of anhydrous aluminum chloride are added. After dissolving the total amount of aluminum chloride (approximately through

10 minutes) 13.6 g of acetyl chloride are added to the solution. Then the mixture is heated for 18 hours with stirring to 105 ° C. The viscous reaction mixture is then cooled to 50 ° C and poured into a mixture of 1000 g of ice and 100 ml.

concentrated hydrochloric acid. Then extracted once with 1400 ml of ether and once with 700 ml of ether; the combined extracts wash twice 2N. 200 ml aqueous solution of hydrochloric acid.

The United aqueous extracts at 40 ° C and at a pressure of 12 mm RT. Art. concentrated to a volume of 400 ml n and then cooled to 4 ° C for 12 hours. The crystals that have been isolated are filtered out and by the addition of active

coal is recrystallized from 5 n. aqueous solution of hydrochloric acid, 33.7 g of 3-acetyl-a, 5-dimethyl-OB-tyrosine hydrochloride are obtained in the form of colorless crystals with m.p. 251--255 ° C.

Example 7. In 300 ml of nitrobenzene, 80 g of aluminum chloride and 39 g of 3-bromo-b-tyrosine are successively added. 13.1 g of acetyl chloride are introduced by dissolution and the reaction mixture is stirred for 18 hours.

at 120 ° C (bath temperature).