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WO1991013068A1 - Procede de fabrication de sulfate-2 dihydrate d'ascorbate dipotassique - Google Patents

Procede de fabrication de sulfate-2 dihydrate d'ascorbate dipotassique Download PDF

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Publication number
WO1991013068A1
WO1991013068A1 PCT/CH1991/000047 CH9100047W WO9113068A1 WO 1991013068 A1 WO1991013068 A1 WO 1991013068A1 CH 9100047 W CH9100047 W CH 9100047W WO 9113068 A1 WO9113068 A1 WO 9113068A1
Authority
WO
WIPO (PCT)
Prior art keywords
keto
reaction
gulonic acid
water
solution
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/CH1991/000047
Other languages
German (de)
English (en)
Inventor
Zeljko Guberovic
Marijan Hohnjec
Tomislav Keglevic
Josip Kuftinec
Milan Oklobdzija
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Enco Engineering Chur AG
Original Assignee
Enco Engineering Chur AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Enco Engineering Chur AG filed Critical Enco Engineering Chur AG
Publication of WO1991013068A1 publication Critical patent/WO1991013068A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D307/62—Three oxygen atoms, e.g. ascorbic acid
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/174—Vitamins

Definitions

  • the present invention relates to a process for the preparation of dipotassium ascorbate-2-sulfate dihydrate of the formula
  • Dipotassium ascorbate-2-sulfate dihydrate is a derivative of Vitamin C (ascorbic acid). It is used, among other things, in fish
  • vitamin C is added to the fish feed.
  • vitamin C is not very stable, especially very sensitive to temperature. In the production and storage of fish feed, up to 65% of the vitamin C used is therefore broken down and lost. However, such a loss does not occur when using the much more stable dipotassium ascorbate-2-sulfate dihydrate instead of vitamin C. Dipotassium ascorbate-2-sulfate dihydrate is therefore used with great success as an additive to fish feed instead of vitamin C (B.W. Tucker, J.E. Halver, Fish Physiol. Boichem., __, 151, (1986)). Fish have the enzyme (sulfatase) required to split off the sulfate residue. This enables your organism to regenerate the pure vitamin C from the stored derivative.
  • vitamin C or one of its salts serves as the starting material.
  • These substances are available on the market (mostly in pharmaceutically pure form); However, they are much too expensive to produce dipotassium ascorbate-2-sulphate dihydrate, which should only be used as an additive to fish feed and therefore does not necessarily have to be of the highest purity. Such a production would not be economical.
  • the invention as characterized in the claims is the object of specifying a process for the preparation of dipotassium ascorbate-2-sulfate dihydrate which is sufficiently pure for fish feed, which starts from a starting material which is also available on the market but is considerably cheaper and which is economically viable with a high yield is more executable than the known methods.
  • Trimethylamine-sulfur-trioxide complex is also available on the market.
  • methyl ester (IIb) is preferably used as the ester.
  • it can also be ethyl ester (IIc), for example.
  • a suitable solution of 2-keto-L-gulonic acid methyl ester (Ilb) in a water / methanol mixture can be easily and also very economically e.g. are obtained by adding sulfuric acid in a catalytic amount to a solution of the monohydrate of 2-keto-L-gulonic acid (Ha) in methanol, precipitating non-esterified acid together with sulfates after a predetermined reaction time and adding the precipitate.
  • diacetone-2-keto-L-gulonic acid (2,3: 4,6-di-O-isopropylide-L-xylo-hexulofuranosonic acid) can also be used with the general formula
  • Diacetone-2-keto-L-gulonic acid is an intermediate product of vitamin C production which is very cheaply available on the market.
  • the economic viability of the process according to the invention is primarily due to the fact that it can be carried out in a single reaction vessel without isolation of intermediate products.
  • the procedural steps required for this can also be carried out beforehand in the same reaction vessel. Acid which has not reacted or sulfates formed are precipitated and separated off.
  • the main reaction path in the method according to the invention should be as shown below:
  • ester is sulfated in enol form; Only then does the lactonization to ascorbate take place.
  • the molar excess in which the trimethylamine-sulfur-trioxide complex is added to the solution of the 2-keto-L-gulonic acid ester in water or the water / methanol mixture is preferably between 4 and 10%.
  • the potassium hydroxide solution added successively to adjust the pH is preferably a 10 N solution.
  • the pH By adjusting the pH to a value between 9.2 and 10.2, the 2-keto group is kept in the enol form.
  • the temperature is preferably adjusted to a value between 40 and 65 ° C during the reaction.
  • the dipotassium ascorbate-2-sulfate dihydrate formed during the reaction is preferably precipitated by adding methanol or ethanol.
  • 10 N potassium hydroxide solution is gradually added to a suspension of 2-keto-L-gulonic acid methyl ester (54 g: 0.26 mol) in water (45 ml) at room temperature until a pH of 8.7 is reached.
  • Trimethylamine-sulfur-trioxide complex 38 g: 0.273 mol is then added, the temperature is raised to 50 ° and the pH is adjusted to 9.99 by further addition of 10 N potassium hydroxide solution. During the following three hours, this pH is maintained by the successive addition of a further 10 N potassium hydroxide solution (a total of 55 ml).
  • the temperature is raised to 60 ° C. and the pressure in the reaction vessel is reduced in order to drive off trimethylamine formed.
  • 10 N potassium hydroxide solution is gradually added to a suspension of 2-keto-L-gulonic acid methyl ester (Ilb) (44 g: 0.21 mol) in a methanol / water mixture (30 ml + 20 ml) a pH of 8.4 is reached. At the same time, the temperature is increased to 58 ° C. Then trimethylamine-sulfur-trioxide complex (32.33 g: 0.23 mol) is added, the pH is adjusted to 10.0 by further addition of 10 N potassium hydroxide solution and the temperature is increased further to 60 ° C. During the following 65 minutes, the pH value of 10.0 is maintained by successively adding a further 10 N potassium hydroxide solution (in total 52 ml) and with stirring.
  • Ilb 2-keto-L-gulonic acid methyl ester

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Polymers & Plastics (AREA)
  • Animal Husbandry (AREA)
  • Zoology (AREA)
  • Engineering & Computer Science (AREA)
  • Food Science & Technology (AREA)
  • Furan Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Steroid Compounds (AREA)

Abstract

Pour la fabrication de sulfate-2 dihydraté d'ascorbate dipotassique, le complexe de triméthylamine-trioxyde de soufre est ajouté, en excès molaire, à une solution concentrée d'un ester de l'acide 2-céto-L-gulonique dans l'eau ou dans un mélange d'eau-méthanol. Le pH de ce mélange réactionnel est ajusté à une valeur comprise entre 9,3 et 10,2, par additions successives d'une solution d'hydroxyde de potassium et est maintenu à cette valeur pendant toute la durée de la réaction. Le procédé est particulièrement approprié pour la fabrication rentable, à l'échelle industrielle, du produit précité, doté d'une pureté suffisante, en vue de son utilisation comme adjuvant pour l'alimentation des poissons.
PCT/CH1991/000047 1990-03-01 1991-02-28 Procede de fabrication de sulfate-2 dihydrate d'ascorbate dipotassique Ceased WO1991013068A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CH00655/90-1 1990-03-01
CH65590 1990-03-01

Publications (1)

Publication Number Publication Date
WO1991013068A1 true WO1991013068A1 (fr) 1991-09-05

Family

ID=4192068

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CH1991/000047 Ceased WO1991013068A1 (fr) 1990-03-01 1991-02-28 Procede de fabrication de sulfate-2 dihydrate d'ascorbate dipotassique

Country Status (1)

Country Link
WO (1) WO1991013068A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110746388A (zh) * 2019-11-06 2020-02-04 宁夏启元药业有限公司 一种古龙酸酯化转化方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2249667A1 (fr) * 1973-11-07 1975-05-30 Kumiai Chemical Industry Co
EP0289894A1 (fr) * 1987-05-04 1988-11-09 F. Hoffmann-La Roche Ag Procédé pour la préparation de dérivés de l'acide L-ascorbique

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2249667A1 (fr) * 1973-11-07 1975-05-30 Kumiai Chemical Industry Co
EP0289894A1 (fr) * 1987-05-04 1988-11-09 F. Hoffmann-La Roche Ag Procédé pour la préparation de dérivés de l'acide L-ascorbique

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Chemical Abstracts, Band 99, Nr. 3, 18. 1983 (Columbus, Ohio, US) siehe Seite 603 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110746388A (zh) * 2019-11-06 2020-02-04 宁夏启元药业有限公司 一种古龙酸酯化转化方法

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