DE1805958C3 - Process for the production of ascorbic acid 3-phosphate - Google Patents

Description

3 4

The hydrolysis proceeds quickly even with the addition of example 3
of water to the reaction mixture. If as a re-

Action product in 5- and 6-position protected 8.3 parts by weight of ascorbic acid and 11.5 GE

Ascorbic acid-3-phosphate is obtained, it will be with parts by weight calcium hydroxide in 30 Rfcum-

a mineral acid (ζ. B. hydrochloric acid and sulfur- b share water dissolved at a temperature below

acid) or acidic ion exchange resins (e.g. sul- 0 ° C are 7.5 parts by weight of phosphorus oxychloride

fonierten polystyrene) in the presence of water of the resulting solution with constant stirring.

hydrolyzed, whereby ascorbic acid-3-phoEphat is obtained. 90 minutes after the addition has taken place

will. stirred at the same temperature. sales

The end product can be in the form of metal salts io is 70.6%. Working up the reaction is isolated be e.g. B. as a sodium, magnesium mixture in the manner described in Example 1 or calcium salt. gives 9.9 parts by weight of the magnesium salt of

The method according to the invention for the preparation of ascorbic acid 3-phosphate, i.e. 70.6% of theory
Treatment of ascorbic acid 3-phosphate is beneficial

for wholesale production, as the desired product 15 Example 4
is selectively obtained in good yield, so that the

Isolation of the desired compound simplifies 10 parts by weight of 5,6-isopropylidene-ascorbic acid

is. and 9.8 parts by weight of sodium carbonate are in

Preferred embodiments of the invention a mixture of 3 parts by volume of water and

are described in the following examples, dissolved in 20 100 parts by volume of dimethylformamide. At a

where parts by weight become parts of volume like grams, temperature below 0 ° C becomes 8.6 parts by weight

behave towards cubic centimeters. Phosphorus oxychloride of the resulting solution under

. added dropwise with constant stirring. After the addition

Example 1 ^ _n J _{nocn we} jt _ere 90 minutes at the same temperature

10 parts by weight of 5,6-isopropylidene-ascorbic acid were stirred at 25 temperature. The conversion is 94.5%. Through

and 21.8 parts by weight of pyridine are worked up in 30 space to that described in Example 1

share dissolved water. Below 0 ° C, 13.1 parts by weight of the magnesium

7.8 parts by weight of phosphorus oxychloride of the obtained salt of ascorbic acid 3-phosphate are obtained, d. s.

Solution was added dropwise with constant stirring. After 94.5% d. Th.

If the addition has taken place, another 90 minutes at the same 30 B is ρ ie 1 5
Chen temperature stirred. The conversion is

94.5%. After the reaction mixture has warmed to 10 parts by weight of so-isopropylidene-ascorbic acid room temperature, it is added to 1 and 9.8 parts by weight of sodium carbonate in a column of sulfonated polystyrene resin in bead form, a mixture of 50 parts by weight of trimethyl (commercially available as »Amberlite IR-120 «®, H ⁺ form, dissolved 35 phosphate and 15 parts by volume of water. Available for one) poured. The process is neutralized with magnesium temperature below 0 ° C, 8.6 parts by weight of oxide and the mixture is evaporated under reduced phosphorus oxychloride with stirring to dissolve the pressure. Add to the residue. Ethanol is added dropwise to the mixture for a further 60 minutes. The resulting white stirred at the same temperature, whereupon powdery crystals are filtered off. Add water to the 40 100 parts of the volume /> ground. The conversion described is 13.2 parts by weight of the 95%. The hydrolyzate obtained is held by the magnesium salt of ascorbic acid 3-phosphate, a column of a sulfonated polystyrene resin in pearls. This salt is passed from a water-ethanol form (commercially available under the name "Amberlite mixture. Yield: 94.5% of the IR-120" ®, H ⁺ form available), whereby

_,, ... _{"Ir nn., A} ,, _n 45, the hydrolyzate is desalted. The expiration is through

Elemental analysis for C ₆ H ₇ O ₉ · P · Mg ■ 4 H ₂ O: _{a column of a strongly basic} anion exchange

Resin of the quaternary ammonium type in bead form (commercially available as "Dowex 1X8, Cl" form "®), the η 2g 5 ° ascorbic acid-3-phosphate ^{contained in the drain is adsorbed on the resin. 1} The resin is mixed with water and then washed with 0.05 N hydrochloric acid, then the ascorbic acid 3-phosphate is eluted with 0.3 η hydrochloric acid, the 10 parts by weight of 5,6-isopropylidene ascorbic acid eluate is neutralized with magnesium oxide and 29.4 parts by weight of magnesium oxide become Then concentrated in 55. 120 Rauin-100 parts by volume of a 2: 1 mixture of water parts ethanol are added to the residue. The white and acetone formed in this way are dissolved. Powdery crystals are filtered off at a temperature below 0 ° C Parts by weight of phosphorus oxychloride of the booty are obtained with 12 parts by weight of the magnesium salt solution, with constant stirring, of ascorbic acid 3-phosphate, ie 95.0%.

stirred at the same temperature. Sales by 1 6
is 78 ° / o. By working up the reaction mixture in the manner described in Example 1, 8.3 parts by weight of ascorbic acid and 15.5 parts by weight of iO.9 parts by weight of the magnesium salt of parts by weight of calcium carbonate are obtained in a Ge - / \ scorbic acid 3-phosphate, ie 78% of theory . 65 mix of 50 parts by volume of trimethyl phosphate and 100 parts by volume of water is dissolved with cooling in the experiment described above. With essentially the same result obtained when a temperature below 0 ° C, 7.5 parts by volume of dioxane is used instead of acetone. Phosphorus oxychloride of the resulting solution

C. H P. Mg Calculated 20.55 4.32 8.84 6.94 Found 20.35 4.26 8.65 7.29 Example el 2

drips. The mixture is stirred for a further 60 minutes at the same temperature, after which 100 parts by volume of water are added. The conversion is 70%. By working up the hydrolyzate obtained in the manner described in Example 5, 8.9 parts by weight of the magnesium salt of ascorbic acid 3-phosphate are obtained; Yield 70.6 Vo of theory

The results of infrared analysis, ultraviolet analysis and electrophoresis for the products obtained in each example agree well with the results match for the authentic sample.

Claims (1)

<l nen. In other words, it is sufficient if the di- Patent claim: Electricity constant of the solvent mixture as such is at least 23 Typical examples Processes for the production of ascorbic acid games of such solvent mixtures are a 3-phosphate by phosphorylation of ascor- 5 1: 1 mixture of acetone and dimethylformamide, bic acid, its hydroxyl groups in 5 and a 2: 1 mixture of water and acetone 6-position are optionally protected, with a 1: 1 mixture of water and dioxane and a phosphoric acid halide in the presence of a 1: 1 mixture of water and pyridine.
a base, characterized as phosphoric acid halides are suitable for that the phosphorylation is carried out in a solution for the purposes of the invention, for example phosphoric acid, whose dielectric chloride, phosphoric acid dichloride, phosphoric acid constant, measured at 20 ° C. and 10 · 10 ^s Hz / fluoride, phosphoric acid bromide, phosphorus oxychloride, künde, 23 and larger is. Phosphorus oxybromide, phosphorus pentachloride and Pyrophosphoryl tetrachloride. 15 The amount of phosphoric acid halide is different depending on the type of solvent that Reaction temperature and the type of halide, however, the halide is generally used in one equimolar amount up to a multiple molar ao ren excess and to achieve the best results Ascorbic acid 3-phosphate was previously used by phosphorylation of ascorbic acid in an equimolar to two-fold molar amount, its hydro- based on the AC,
icyl groups in the 5- and 6-position with a Ascoi binsäuren, whose hydroxyl groups in Phosphoric acid halide protected or unprotected in the 5- and 6-positions can be generalized, i 1 a lower aliphatic ketone (ζ. B. as mean the condensation products of C ₃ - to C ₁₀ -aeetoia, methyl ethyl ketone, methyl isobutyl ketone) in ketones and ascorbic acid can be used. Presence of a base produced. This well-known typical example of such ketones is acetone, but the method has disadvantages. For example, there is methyl ethyl ketone, diethyl ketone, cyclopentanone and a non-specific phosphorylation on both hy-cyclohexanone. In general, the use of hydroxy'-groups in the 2- and 3-positions of the ascorbic acid of isopropylidene ascorbic acid is most advantageous, acidic instead, so that the yield of the desired for the process according to the invention can be achieved Ascominic acid 3-phosphate is inevitably bad. inorganic or organic bases are used. Suitable inorganic bases are, for example, separation of ascorodic acid 3-phosphate from ascoric alkali metal hydroxides, e.g. B. sodium hydroxide, cabinic acid-2-phosphate and others in less than 35 liumhydroxyd, alkaline earth metal hydroxides, z. B. calcium amount formed phosphorylation products er hydroxide and barium hydroxide, alkali carbonates, necessary (Gazz. Chem. Ital., 91, 964 to 972, 1961, z. B. sodium carbonate and potassium carbonate, Erdreferiert in CA, Vol. 56, 8827 c , 1962). alkali carbonates, e.g. B. Calcium hydrogen carbonate and It has now surprisingly been found that magnesium hydrogen carbonate, metal oxides, e.g. B. exclusively the hydroxyl group in the 3-position 40 calcium oxide and magnesium oxide, and ammonia, the ascorbic acid is selectively phosphorylated when the organic bases are, for example, one suitable for ^r according to ascorbic acid regardless of the various aliphatic amines such. B. Didarauf. whether their hydroxyl groups in 5- and 6-stelmethylamine, trimethylammine, triethylamine and dilution are protected, with a phosphoric acid halocyclohexylamine, and aromatic or cyclic genide in a solvent that converts a di- 45 amine, z. B. dimethylaniline, pyridine, N-Methylmorelektrizitätskonstante has at least 23, Ge pholin, N-ethylpiperidine, lutidine, collidine and measured at 20 ⁰ C and 10 x 10 ³ Hz. Quinoline. The base must be at least in an equi-The starting material, ie ascorbic acid, the molar amount thereof, based on A.C., who protected or the hydroxyl groups in the 5- and 6-positions. It is more expedient to use the base when it is unprotected, it will be referred to below as "AC" excess and, to achieve the best results, it will be used. The dielectric constants given here of 2 to 20 times the equimolar constant were all at 20 ° C. and 10 · 10 ^s Hz. In the case of a strong alkali, as measured. Sodium hydroxide or potassium hydroxide, it is. For the purposes of the invention, it is advisable to use solvents not more than 8 times the amount of the medium which uses a dielectric base, based on A.C., in order to achieve the BiI constant of at least 23 and do not affect the reaction of various phosphates as reaction products. As examples of suitable inputs to be avoided. cell solvents which have the values given in brackets. The reaction takes place in a short time, e.g. B. 10 minutes Have dielectric constants: up to a few hours, when they are in the Acetonitrile (36.6), methanol (32.6), glycerin (42.5), 60 near 0 ° C. However, it can Nitrobenzene (34.8), dimethylformamide (36.7), tri- also at higher or lower temperatures methyl phosphate (24.0), N-methylacetamide (165). With better results it is Water (80) and formamide (109). however, to be expected if the reaction is below If solvent mixtures are used, 15 ⁰ C is carried out. must have at least one of the solvents that produce the 65 If the product is an ascorbic acid c-3-halogen mixture form, a dielectric constant of phosphate derivative is obtained, this becomes more common Have at least 23 while the values for the way hydrolyzed, being ascorbic acid-3-phosphate other solvents lower than 23 can be obtained in good yield and high purity.