OXONIC ACID POTASSIUM SALT(link:https://www.bloomtechz.com/synthetic-chemical/oxonic-acid-potassium-salt-cas-2207-75-2.html) is also known as oteracil potassium (0teracil Potassiym), chemical name 1, 4, 5, 6-tetrahydro-4, 6-dioxo-1, 3, 5-triazine-2-carboxylate potassium . As one of the main components of a compound anticancer drug, fluterazine (TS-1), although it does not exhibit antitumor activity itself, it remains in the gastrointestinal tract and can inhibit 5-fluorouracil (5-FU) Activation at this position, thereby inhibiting the toxic and side effects of the antineoplastic drug tegafur, potassium oxonate can selectively act on orotate phosphoribosyltransferase in the gastrointestinal tract, block fluorouracil phosphorylation, reduce The resulting toxic and side effects of the gastrointestinal tract, potassium oxonate can also inhibit the reduction in food intake of the tested animals, thereby improving the symptoms of animal weight loss.
The first method is to be starting raw material with allantoin, under liquid bromine, KI effect, be converted into six-membered ring by five-membered ring, then salt in KOH aqueous solution, obtain potassium oxonate, yield 70%, No refining method is provided, nor is product purity stated.
1. Oxidative ring-opening reaction:
a. Dissolve allantoin in a suitable solvent, such as water.
b. Add liquid bromine (Br2) and potassium iodide (KI), and stir the reaction mixture well.
c. After the reaction has been carried out for a period of time, the product will undergo a structural change to form a six-membered ring compound.
The chemical equation for this reaction is as follows:
C4H6N4O3 + Br2 + 2KI → six-membered ring compound + 2KBr + I2
2. Salt formation reaction:
a. Dissolve the six-membered ring compound prepared above in an aqueous solution of potassium hydroxide (KOH).
b. Stir the mixture and let it react for a while.
c. After the reaction, remove excess impurities by filtration or other methods.
d. Crystallization of the salt of potassium oxonate.
The chemical equation for this reaction is as follows:
Six-membered ring compound + KOH → C4H2KN3O4
The British literature provides a method for synthesizing potassium oxonate, using 2,2-diureidomalonic acid or its decarboxylated product diureidoacetic acid (alantoic acid) as the starting material respectively, which is oxidized to cyclic , Salt under alkaline conditions in the system, the crude product is not refined, the yield is only 48%. The detailed steps are as follows:
Step 1: Oxidation to ring
2,2-diureidomalonic acid undergoes an oxidation reaction to form an oxazolidine structure.
Chemical formula:
2,2-Diureidomalonic acid + polar solvent + O2 → C3H5NO2
Step 2: Decarboxylation
Under alkaline conditions, the carboxyl group (COOH) in oxurea is detached to form carboxylate.
Chemical formula:
C3H5NO2 + base → carboxylate
Step 3: Saltification reaction
Reaction of carboxylate with appropriate potassium salt produces OXONIC ACID POTASSIUM SALT (Oxazolidine Glycopolypeptide Salt).
Chemical formula:
Carboxylate + potassium salt → C4H2KN3O4
It is also the same British author who published another method for this product. The steps of synthesizing OXONIC ACID POTASSIUM SALT using diureidoacetic acid (alantoic acid) as the starting material are similar to the above steps, except that there is a slight difference in step 1. the difference:
Step 1: Oxidation to ring
Diuretoacetic acid undergoes an oxidation reaction to form a vinylacetamide structure.
Chemical formula:
Diuretoacetic acid + polar solvent + oxygen → vinylacetamide
Subsequent steps (decarboxylation and salinization reactions) are the same as those described above.
The yield of this method is 82%, and the recrystallization in gained crude product 80g (0° C. of hot water obtains acicular crystal twice, m.p. > 300 ℃, does not mention purity, the contriver high-performance liquid phase analysis finds, by this method refining though The color changed to some extent, but the two impurity peaks that appeared in about 4 to 5 minutes not only were not refined but increased, probably because potassium oxonate was heated in 80g (°C) hot water
caused by decomposition.
For the potassium oxonate product obtained in the above technology has many impurities and low purity, it cannot reach the relevant standards and cannot meet the requirements of the pharmaceutical industry.
According to the requirements of pharmaceutical preparations, the purpose of our company is to provide an effective refining method for purifying potassium oxonate. Scientific research personnel analyzed by high-performance liquid phase-mass spectrometry (chromatographic conditions use octadecyl silane and silica gel as filler, use acetonitrile-0.010mol/l bromohexadecyl trimethylamine solution (65: 35) with triethylamine Adjust the pH value to 9 as the mobile phase, the detection wavelength is 264 °C, and the number of theoretical plates is not less than 5000 according to the peak of oxonic acid potassium) to find impurities, determine and formulate a purification scheme according to the structure and physical and chemical properties of the impurities. This invention can Effectively remove impurities and prepare high-purity potassium oxonate, which has the advantages of simple and convenient operation, mild reaction conditions, and high yield. The yield is more than 90%, and the purity is more than 99.95M (HPLC detection), and the single impurity peak is reduced by 0.5%. To below 0.05%. The advantage of this method is that there is no complicated reaction process, it can be carried out at normal temperature, the operability is strong, it is not easy to cause side reactions, the yield > 90%, the purity is more than 99.95% (HPLC detection), and the single impurity peak is formed by 0.5% to below 0.05%.