SU1293171A1 - Method of producing n-acetyl-d,l-alanine - Google Patents

Abstract

The invention relates to amino acid derivatives, in particular, the N-acetyl derivative of 0-b-apanine, which is used as cfé, in organic synthesis, for example, to obtain the optically active amino acids L-alanine and H-acetyl-B-apanine with aminoacylase or D-alanine by chemical hydrolysis. Simplification of the process is achieved by the fact that a1 dl L-anaHHHa is stratified with acetic anhydride in acetic acid, taken in a molar ratio of 1: 1.2-1.3: 4.4-5.0, at 48-55 & ° C for 20-30 minutes The desired product is isolated from water without ion exchange purification. The method allows to simplify and cheapen the process by reducing the consumption of acetic acid and its anhydride, as well as to eliminate ion-exchange purification. 2 tab. a (o

Description

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The invention relates to an improved method for the preparation of the N-acetyl derivative B, 1-alanine. N-Aceti-B, L-alanine is widely used in fine organic synthesis, it is used as a raw material for the production of optical active amino acids L-alanine and N- -acetyl-O-alanine using amino acylase, as well as D-alanine. using chemical hydrolysis.

The purpose of the invention is to simplify the process.

The goal is achieved by the fact that the process is carried out at 48-55 s for 20-30 mi with a molar ratio of amino acid – acetic anhydride – acetic acid equal to 1: 1.20–1.30: 4.4–5.0 . The desired product separates from the water without ion exchange purification.

The method makes it possible to obtain the target product with a yield of 78-83% and a purity of 98.7-99.0%.

Example 1 In a tetragon) four-liter round-bottomed flask equipped with a stirrer, a thermometer, a reflux condenser and an addition funnel, 534.2 g (6 mol) of D, L-alanine, 1500 ml (26.2 mol) of acetic acid are placed and the reaction mixture is heated with stirring weight up to 48-50 ° C. While maintaining this temperature for 20 minutes, 720 ml (7.2 mol) of acetic anhydride was added. Then the solvent is distilled off in vacuum at 45-50 ° C. With this, 1800 ml of acetic acid with a content of 0.6% acetic anhydride is obtained, which is reused for the same purpose.

The reaction product is dissolved in 400-500 ml of distilled water, and the water is evaporated under the same conditions. The precipitate containing L-acetyl-B, L-alanine is dissolved in a miniature volume of water and crystallized by gradually lowering the temperature to OC. The precipitated crystals are separated on a Buchner funnel and dried under vacuum at 40 ° C or in air.

653 g of L-acetyl-B, L-alanine are obtained, which is 83% of the theoretical per B, L-alanine. The content of the main substance 99,0% So pl. 135.5-136 ° C. The product is chromatographically homogeneous.

Found,%: With 45.62; H 7.06; N 1 1.88.

Calculated,%: C 45.80; H 6.92; N I1.96,

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Example 2. The process is carried out analogously to example I, with the difference that the ratio of amino acid to acetic anhydride is acetic acid: 3: 5.0 j and the process temperature is 53-55 ° C. From 534.2 g (6 mol) of D, L-alanine, 1717 ml (30 mol) of acetic acid and 780 ml (7.8 mol) of acetic anhydride, 630 g (80% of theoretical) of N-acetyl-B , B-alanine. Content of the main substance is 99,0%. M.p. 135-136 ° C.

Found,%: With 45.62; H 7.06; N-11.88.

Calculated,%: C 45.80; H 6.92; N 11.96 ..

Example 3: Preparation of N-acetyl-D, L-alanine in pilot plants under production conditions. The selection of the desired product is carried out in two steps. The crystals of N-α-acetyl-D, L-alanine are separated in a centrifuge.

A 10.07 kg (113 mol) of D, L-alanine and 27.0 l (469.9 mol) are placed in a glass reactor of the brand Si-max with a capacity of 75 l equipped with a stirrer, a thermometer, a 20-meter measuring device and a heating coil. acetic acid. 1 steam in a coil and with stirring, preheat the contents of the reactor to 48-50 ° C. Keeping this temperature from the measuring device, 14.13 liters (141.25 mol) of acetic anhydride are added within 25-30 minutes. The contents of the apparatus are then transferred to a Simax vacuum circulation apparatus with a capacity of 25 and a capacity of 25 l / h and the solvent is distilled off. 7.5 liters of water is added to the bottom residue containing N-acetyl-D, L-alaanin as an oil. Water was evaporated under the same conditions until the first H-acetyl-B5L-alanine crystals were formed. Then 6 l of water are added and, after good mixing, they are transferred to an enamelled vat equipped with a stirrer, a thermometer and a brine line. Open the brine and gradually reduce the temperature of the mixture to 0 ° C for 2.5 3 hours.

N-Acethyl-D, L-alanine is separated in a TB-600N centrifuge, 3000 v / m

Colorless crystals 11; the gallstone product is dried at 30–40 ° C in vacuum for 6 hours or in air at 20 for 24 hours.

10.0-11.0 kg of N-acetyl-D, L-alanine are obtained;

The mother liquor is concentrated in vacuo to give n, j, l, 410-1.420 and crystallized under the same conditions. Additionally, 0.9-1.6 kg of the desired product is obtained.

The total yield of H-acetyl-B, L-alanine is 11.6-11.9 kg (78-80% of the theoretical per B, L-alanine). Content of the main substance is 98.7%. M.p. I35-136-C.

The product is chromatographically homogeneous.

Found,%: C 46.09; H 7.21; N 11.98

Calculated,%: C 45.80; H 6.92; N 11.96.

In tab. Figures 1 and 2 show the results of comparative examples of the acetylation process at different temperatures and different ratios of reagents.

From tab. I, it can be seen that the temperature range of 48-55 ° C is optimal, since raising or lowering the acetylation temperature from the optimum 48-55 ° C does not lead to better results.

From tab. 2 it becomes apparent that the optimum ratio of alanine

67.3

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acetic anhydride - acetic acid is 1: 1.20-1.30: 4.4-5.0, because a decrease in the amount of acetic anhydride and acetic acid

 leads to incomplete reaction, and the increase does not have a perceptible change, but only leads to an over-consumption of raw materials.

The method allows to simplify and reduce the process by reducing the consumption of acetic acid and acetic anhydride, avoiding ion-exchange purification. A positive effect is also achieved by lowering the temperature of the acetylation reaction (5 rounds) and reducing environmental pollution.

Claims (1)

Invention Formula The method of obtaining K-acetyl-B, L-α-alanine by acetylation-D, L-alanine with acetic anhydride in acetic acid when heated, followed by separation of the target product from water, characterized in that, to simplify the process, acetylation is carried out at a temperature 48-55 with a molar ratio of - 30 scientific research institute B, L-alanine - acetic anhydride - acetic acid, equal to 1: 1.20 - 1.30: 4.4 to 5.0. 20 25 Table 1 Lack of 135-136 vuat The same135-136 - -135-136 - -135.5-136 1.6130-136 12931716 table 2 Compiled by L.Ioffe Editor M.b) Shyn Tehred A.Kravchuk Order 343/25 Circulation 372Subscription VNIIPI USSR State Committee for inventions and discoveries 113035, Moscow, Zh-35, Raushsk nab., 4/5 Production and printing company, Uzhgorod, st. Project, 4 Proofreader N.Korol