DK146622B - PROCEDURE FOR PREPARING AMINO ACIDS FROM THE SIMILAR N-CARBAMYLAMINOS ACIDS - Google Patents

Description

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f, i2) PUBLICATION MANUAL (n) 146622 B

DIRECTORATE OF THE PATENT AND TRADEMARKET SYSTEM

(21) Patent Application No. 1546/76 (51) Int.CI.3: C 07 C 99/00 (22) Filing Date: 31 Mar 1976 (41) Aim. available: 10 old 1976 (44) Submitted: 21 Nov 1983 (86) International Application No: - (30) Priority: 09 Apr1975IT22144 / 75 (71) Applicant: * ANIC S.P.A.; Palermo, IT.

(72) Inventor: Francesco 'Cecere; IT, Walter 'Marconi; IT, Franco 'Morisi; IT, Bruno 'Rappuoli; IT.

(74) Plenipotentiary: International Patent Bureau_ (54) Process for the preparation of amino acids from the corresponding N-carbamylamino acids

The present invention relates to a process for preparing amino acids from the corresponding N-carbamylamino acids.

It is known that optically active N-carbamyl derivatives of amino acids can be recovered from the corresponding racemic hydantoins by stereo-selective enzyme hydrolysis, as described in DE Patent No. 24,227,377.

The N-carbamyl derivative thus obtained was then converted to the corresponding amino acid by simply boiling it in an aqueous solution.

Imidlertid However, the hydrolysis of N-carbamyl derivative to amino acid produced under such conditions is very slow and requires close control of the working conditions and sometimes gives rise to by-products resulting in diminishing yield and even partial racemization.

2 1A 6 6 2 2

The present invention provides a novel and simple method for preparing amino acids from the corresponding N-carbamylamino acids, which preparation takes place under mild conditions such that the produced amino acid still has the same optical purity as the starting material used as N-carbamyl derivative.

The process of the invention is characterized in that the N-carbamyl derivative or a salt of this derivative in aqueous solution is reacted with 1 to 1.5 equivalents of nitric acid or a salt thereof in the presence of an acid group-containing cationic ion exchange resin used in an aqueous solution. such that it can bind 1-5 moles of product per mole of N-carbamylamino acid, at a temperature of from 0 to 40 ° C, after which the compound formed is eluted from the resin with a base.

The course of this process was very surprising in that it is known that oxidizing agents act on the amino acid of the amino acid during immediate conversion of the amino acid to the corresponding hydroxy acid, thus making it impossible to recover the amino acid.

However, it has been found that when employed at the temperature conditions prescribed for the process of the invention and the pH conditions of the ioribylate resin present, the amino group is completely free from attack by the oxidizing reactant and surprisingly high yields of the amino acid.

The above-described process is carried out by dissolving the N-carbamyl derivative, or a salt thereof, in variable concentration water, preferably near saturation. To the solution is added an acid group-containing cationic ion exchange resin having the above-mentioned binding ability. During this step, the pH decreases and the N-carbamyl derivative which, as a result, is in excess of its solubility is precipitated. Add from 1 to 1.5 equivalents of nitric acid or a salt thereof, the whole reaction being carried out at a temperature in the range of 0 ° C to 40 ° C.

As cationic resins, resins having different acidic groups can be used, but the resin used according to the invention is preferably of the sulfonic acid type.

Upon completion of the reaction, the amino acid is eluted from the resin with a base and the resin can again be acidified. From the eluate, the amino acid is isolated by simple concentration and crystallization operations.

The process according to the invention is further described by the following examples.

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Example 1 (Comparison) 50 ml of a 25 mM solution of N-carbamyl-α-alanine was treated at 0 ° C with 5 ml of a 50 mM solution of NalW 2 in water. The concentration of the amino acid in the solution was occasionally measured. After the concentration reached a ceiling of 5mM during the first hour of reaction, it slowly decreased and after 5 hours dropped to 3.2mM.

Chromatography analysis of the mixture showed the presence of a significant amount of lactic acid.

Example 2 194 g (1 mole) of D-N-carbamyl-phenylglycine with an optical purity of 99% were slurried in 10 liters of deionized water in the presence of 8 liters of VAmberlite 120 (H +). While stirring the solution at room temperature, 83 g (1.2 mol) of sodium nitrite was added. After approx. For 2 hours, the resin was filtered off, washed twice with 10 liters of demineralized water and then transferred to a column (diameter 11 cm, height 1 m). The resin was then eluted with 2M ammonia. All the amino acid was present in the fraction of 10 to 15 liters of eluate.

The 5-liter solution of the ammonium salt of D-phenylglycine was evaporated to dryness under reduced pressure. This yielded 150 g (99% of theory) of D (-) - phenylglycine with [of] _ = -157 ° (c = 0.5, HCl 1N), which is an optical purity higher than 987 ° at as [a ] ^ to take the value from the technical literature (Org.

Synth. 22, 23, 1942).

Example 3

Using the same procedure as in Example 2, but starting from 132 g (1 mole) of LN-carbamyl-α-alanine with an optical purity of 98%, 87 g (0.98 mole) of La-alanine were obtained with [ a] + = 14.3 ° (c = 2, HCl IN) (from the literature [a] + = 14.7 °, J. Chem. Soc. 113, 526, 1918).

Example 4

Using the same procedure as in Examples 2 and 3 and from 160 g (1 mole) of LN-carbamyl-valine with an optical purity of 97%, 110 g (0.94 mole) of L-valine was obtained, [ = 28.2 ° (c = 3, HCl 6N), (from the literature [a]

Ber. 39, 2320, 1906).