Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1991-10-25
1993-05-11
Tsang, Cecilia
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
549315, C07D30762, C07F 906
Patent
active
052102203
DESCRIPTION:
BRIEF SUMMARY
The invention is concerned with a process for the manufacture of ascorbyl phosphates, namely of phosphates of the formula ##STR2## wherein M.sup.k.sym. denotes a cation, k.sup..sym. denotes the valency and m denotes the equivalents, with the proviso that the product from k.m=3, by phosphorylating ascorbic acid.
k is 1 to 3, especially 1 or 2.
The process comprises using pre-formed sodium (or potassium) dichlorophosphate as the phosphorylating reagent, adding ascorbic acid to this pre-formed phosphorylating reagent in aqueous solution, especially at pH values between about 11.0 and about 13.0, in the presence of a water-soluble trialkylamine as the catalyst and at temperatures between about +10.degree. C. and about -8.degree. C., especially at temperatures below 0.degree. C., and, if desired, trans-salting the I which is obtained as the sodium (or potassium) salt and/or, if desired, purifying via an amine salt.
The preparation of the phosphorylating reagent is preferably carried out in situ, namely from POCl.sub.3 and aqueous NaOH or KOH. The ratio of POCl.sub.3 :base is conveniently about 1:1.5 to about 1:2.5, preferably about 1:2.
The reagent is prepared in a pH range of about 4-11, with the preferred procedure being carried out in a neutral medium.
the phosphorylation is conveniently carried out at temperatures of about -8.degree. C. to about +10.degree. C., with temperatures below 0.degree. C. being preferred. This also applies to the separation of the alkali salts described below.
The ascorbic acid is now added to the thus-prepared phosphorylating reagent which is in solution or, if desired, in suspension. This addition is conveniently effected at pH values between about 11 to 13 and at the above temperatures.
The addition of the ascorbic acid to the pre-formed phosphorylating reagent leads to the selectivity which is striven for: the temperature can be held low in a much simpler manner: part of the heat liberated during the hydrolysis is, of course, already dissipated.
A convenient ratio of ascorbic acid:phosphorylating agent is that of about 1:1 to about 1:1.5, with the preferred range lying at about 1:1.35.
The manufacture of the salts I is effected with the addition of a catalyst, namely a water-soluble tert. amine.
The tert. amine is conveniently acyclic, monocylic or bicyclic.
Examples of preferred water-soluble amine are amines having the following groupings: ##STR3## Timethylamine is preferred.
The convenient ratio of ascorbic acid:amine is about 1:0.2 to about 1:1, with the preferred range being 1:0.5.
The addition of the ascorbic acid to the pre-formed phosphorylating reagent is thus effected in a strongly alkaline range.
Spontaneous crystallization of the alkali phosphate takes place, with the Na salt being preferred over the K salt.
After its separation, the trisodium or tripotassium salt I which is present in the filtrate can be trans-salted using a solution of a water-soluble metal salt, whereby the respective most insoluble salt I can be precipitated.
Ca.sup.2+ and Mg.sup.2+ are in the foreground of interest here. A chloride is preferably used, but the anion of another mineral acid, for example the nitrate, also comes into consideration.
The preferred concentrations lie in the range of a few mol/liter, e.g. about 1-2 mol/l.
The further purification of the phosphates I (M=Na, K) is preferable carried out with the aid of so-called "crystallization bases" which form salts with acids, in the present instance with the "acidic" form of I.
Especially suitable crystallization bases are bicyclic and tricyclic amino compounds, for example 1- or 2-amino-adamantane, (+)-dehydroabietylamine, etc.
Especially suitable are amino compounds which have the camphane (bornane) or pinane structure, such as e.g.
From this list it will be evident that the lower limit of C atoms in the ring is preferably 9.
Those phosphates I which have as the cation an ammonium ion corresponding to one of the above amino compounds crystallize especially readily, for example from a mixture of lower alcohols, e.g. methanol/water.
REFERENCES:
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patent: 4179445 (1979-12-01), Seib et al.
patent: 4251449 (1981-02-01), Schreur
patent: 4997958 (1991-03-01), Pauling et al.
patent: 4999437 (1991-03-01), Dobler et al.
patent: 5110950 (1992-05-01), Seib et al.
patent: 5110951 (1992-05-01), Ishimura et al.
patent: 5118817 (1992-06-01), Toshida et al.
Lee et al., Carbohydrate Research, vol. 67, pp. 127-138 (1978).
Nomura et al., Chem. Pharm. Bull., vol. 19, pp. 1433-1437 (1971).
Computer Search Abstract.
Pauling Horst
Wehrli Christof
Epstein William H.
Gould George M.
Hoffmann-La Roche Inc.
Tsang Cecilia
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