DE1183093B - Process for the production of homocysteinic acid - Google Patents

Description

GERMAN

PATENT OFFICE

EDITORIAL

German KLc 12 q - 6/03

Number _:; 1183 093

File number; A 38256 TVb / 12 q

Filing date: September 5, 1961

Opening day: December 10, 1964

The invention relates to a simple and in wirtt economically feasible process for the production of homocysteic acid, after which one Acrolein or a gas mixture containing acrolein - which in turn is produced by air oxidation of Propylene has been obtained - in an aqueous containing a suitable amount of sodium hydrogen sulfite Introduces solution, the resulting solution with an aqueous, cyanide ions, carbonate ions and ammonium ions Reacts containing solution and hydrolyzed the product obtained.

It is already in the literature (e.g. by L. W. Butz and V. de Vigneaul, in J. Biol. Chem., 99 [1932-1933], p. 135) that homocysteic acid by oxidation of homocysteine with Bromine is obtained. However, apart from the melting point, there is hardly anything about his at this point physical properties indicated. In the older literature there is a large number of Manufacturing processes for homocysitein are described, however none of them are simple enough for that Practice.

The method of the invention has the advantage over the known methods that you neither the difficult to synthesize homocysteine nor the difficult to handle bromine, but that instead, acrolein is used and homocysteic acid is used in a relatively simple procedure easily obtained in an economical manner.

The carbonate, cyanide and ammonium ions required according to the invention can be in the form of Salts, free acids or ammonia are added. So z. B. ammonium cyanide or Alkali cyanide can be used together with ammonium carbonate. The hydrolysis can according to Invention can be carried out in the usual manner, e.g. B. by means of alkali hydroxide. The one in hydrolysis Homocysteic acid formed can be isolated in a known manner, for. B. by the hydrolyzed Concentrated solution, the precipitated inorganic salts filtered off and finally the solution obtained cleans with ion exchange resins.

example 1

14.0 g (0.25 mol) of freshly distilled acrolein were added dropwise with stirring to a suspension of 52 g (0.5 mol) of sodium hydrogen sulfite in 80 ecm of water. In order to avoid a temperature increase as a result of the heat of reaction associated with the addition of acrolein, the solution was kept below 20 ° C. by cooling. Stirring was continued for an additional 30 minutes after the addition was complete. Homocysteine _acid:

Applicant:

Ajinomoto Kabushiki Kaisha, Tokyo \

Representative: , . ■

Dr. G. W. Lotterhos and

Dr, -Ing. H, -W. ^! Lotterhos; Patent Attorneys, Prankfurt / M ;, Anriastr. 19th

Named as inventor:

Takeo Kaneko, Osaka-Shi, Osaka-fu, Ryonosuke Yoshida, Suita-shi, Osaka-fu, Takeshi Hayama, Hodogaya-Ku, Yokohama-shi, Masahiko Täkesada,

Kamakura-shi, Kanagawa-kep (Japan)

Claimed priority:

Japan 6 September 1960 (37 009)

continued to stop the reaction. Then the reaction mixture was added to a stirred suspension of 26.4 g (10.275 mol) of ammonium carbonate in 190 cc of a 20 ⁰ / o ammonia solution containing 12.1 g (0.275 mol) ammonium cyanide containing not exceeding at a 20 ° C temperature were added dropwise and then." Maintained at 55 to 60 ° C with heating for 3 hours. The reaction was terminated by maintaining the temperature at 60 to 70 ° C. for a further hour. 78 ecm of 16 η sodium hydroxide solution were added to the solution of the reaction product obtained in this way and the mixture was hydrolyzed by heating at 200 ° C. for 30 minutes in an autoclave.

After concentrating the hydrolyzed solution and removing the excess ammonia the concentrate was redissolved in water through a layer of strongly acidic ion exchange resin out and the eluate from which the cation such. B. sodium ion, has been removed by adsorption was collected. The resulting solution was concentrated, then alcohol was added, whereby colorless Crystals precipitated which, after cooling, were filtered off, washed with alcohol and dried. the Yield was 28.3 g (62% of theory - based on acrolein), melting point 261 to 262 ° C (decomposition

409 757/386

T 183

setting). After recrystallization from water and Alcohol had a melting point of 265 to 266 ° C. (decomposition).

Analysis for C ₄ H ₉ NSO ₅ :

Calculated .... C 26.23 Vo, H 4.95%, N 7.65%; found C 25.95%, H 5.25%, H 7.36%.

In the paper chromatogram of these crystals, developed on “Toyo Roshi No. 50 «, using a solvent mixture consisting of n-butanol, acetic acid and water in a volume ratio of 4: 2: 1 as developer, only one spot of the Rf value of 0.083 was obtained, the was identical to that from an authentic homocysteic acid sample.

Example 2

A mixture of propylene and air, which contained selenium vapor, was ao with cuprooxide coated aluminum catalyst, which was kept at 300 ° C, passed, the oxidizing gas mixture thus obtained in 120 ecm of an aqueous solution containing 60.4 g (0.577 mol) of sodium hydrogen sulfite initiated and the acrolein collected. After introducing 12.41 (about 0.5 ecm) of the oxidation mixture the free sodium hydrogen sulfite in the aqueous solution had disappeared. 130 ecm the aqueous solution thus obtained, which contained an adduct of acrolein with sodium hydrogen sulfite, were a suspension of 0.32 mol of ammonium cyanide and 0.32 mol of ammonium carbonate in 210 ecm 20% aqueous ammonia at 20 ° C does not Exceeding temperature was added dropwise with stirring. The temperature was increased to complete the reaction Maintained at 60 to 70 ° C for another hour. The reaction product thus obtained was added with 90 ecm 16 η sodium hydroxide solution, the hydrolysis was carried out by heating to 200 ° C. for 30 minutes heated in the autoclave. The further work-up was then carried out as described in Example 1 Manner to obtain 33 g of homocysteic acid.

Example 3

45

A suspension of 20.2 g of sodium hydrogen sulfite in 30 ecm of water was initially added with stirring 5.6 g of acrolein at 5 to 10 ° C and then after 15 minutes a solution of 5.4 g of sodium cyanide in 20 ecm of water were added dropwise, with inorganic crystals separating out, which were filtered off after 30 minutes became. The filtrate obtained was with 50 ecm of water, 45.6 g of ammonium carbonate and 100 ecm of methanol are added, then kept at 50 to 60 ° C. for 4 hours with stirring, then through Filtration freed from a small amount of insoluble substances, the pH of the obtained The filtrate was adjusted to unity with hydrochloric acid, the solution heated for 1 hour and then concentrated. The residue was then passed through a column (5 cm in diameter and 50 cm in length) with the ion exchange resin »Diaion SK No 1« (trade name) and the acidic fractions were collected. The combined fractions were concentrated to a syrup, which is in Dissolved water, neutralized with sodium hydroxide and then concentrated. After removing the failed inorganic substances by filtration were obtained by adding methanol to the filtrate 4.5 g of crystalline sodium johydantou diethane sulfonate obtain. Another 4.0 g of crystals were recovered from the mother liquor.

After recrystallization from water-methanol, the crystals had a melting point of 205 bis 210 ° C (decomposition) and the following values at the Elemental analysis:

C ₅ H ₇ O ₆ N ₂ Na:
Calculated
found .

C 26.08%, H 3.08%, N 12.17%; C 26.02%, H 3.25%, N 11.24%.

To a solution of 3 g sodium - /? - hydantoinethanesulfonate 12 g of barium hydroxide in 100 ecm of water were added and the mixture was then heated for 8 hours and dry ice is added to the hydrolyzate in order to convert excess barium hydroxide into barium carbonate, which was filtered off. The filtrate obtained was adjusted to pH 1 with dilute sulfuric acid and the precipitated barium sulfate was filtered off. The filtrate was concentrated, the residue obtained was dissolved in water and alcohol was added to give homocysteic acid in crystalline form to fail. This gave 1.5 g of crystals which, after recrystallization from water and alcohol, became one M.p. of 266 to 267 ° C (decomposition).

Claims (1)

Claim: Process for the production of homocysteic acid, characterized in that one acrolein or an acrolein-containing oxidizing gas mixture, which by air oxidation of propylene was introduced into an aqueous solution containing an appropriate amount of sodium hydrogen sulfite, the obtained Reacts solution with an aqueous, cyanide, carbonate and Ammondumionen containing solution and hydrolyzing the product obtained. Elderly Rights Considered:
German Patent No. 1151 510. «9 757ß86 12.64