A method of producing 5-fluorouracil which includes the fluorination of uracil with elementary fluorine diluted with an inert gas in a glacial acetic acid medium under hydrodynamic conditions of Re=35,000-45,000 at a temperature of from 15.degree. to 35.degree. until the uracil disappears from the reaction mixture, whereafter said mixture is heated at a temperature of from 90.degree. to 95.degree.C until 5-fluoro-6-acetoxy-dihydrouracil formed during the fluorination disappears therefrom, followed by isolation of the desired product. The 5-fluorouracil compound is useful as a chemotherapeutical remedy for treating cancer of the alimentary tract and also as a starting material for synthesizing other antitumoric substances.
Direct fluorination of uracil, cytosine and their derivatives, in the presence of a non-aqueous solvent, by fluorine gas to produce 5-fluorouracil, 5-fluorocytosine, 5-fluorouracil derivatives and 5-fluorocytosine derivatives is disclosed. The non-aqueous solvent is an acid or alcohol, which can be partly or fully fluorinated or chlorinated, of up to 8 carbon atoms, such as trifluoroacetic acid. Novel compounds produced by the reaction, such as 5,5-difluoro-5,6-dihydro-6-(2,2,2-trifluoroethoxy) uracil are also disclosed. The derivatives and 5-fluorocytosine are useful as germicidal and antineoplastic agents while 5-fluorouracil itself is a known cancer chemotherapy agent.
Direct fluorination of uracil, cytosine and their derivatives, in the presence of a non-aqueous solvent, by fluorine gas to produce 5-fluorouracil, 5-fluorocytosine, 5-fluorouracil derivatives and 5-fluorocytosine derivatives is disclosed. The non-aqueous solvent is an acid or alcohol, which can be partly or fully fluorinated or chlorinated, of up to 8 carbon atoms, such as trifluoroacetic acid. Novel compounds produced by the reaction, such as 5,5-difluoro-5,6-dihydro-6-(2,2,2-trifluoroethoxy) uracil are also disclosed. The derivatives and 5-fluorocytosine are useful as germicidal and antineoplastic agents while 5-fluorouracil itself is a known cancer chemotherapy agent.
5-fluorocytosine is prepared by reacting 2,5-difluoro-4-chloro-pyrimidine with a proton acid in the presence of water to yield 2-hydroxy-4-chloro-5-fluoropyrimidine and reacting the 2-hydroxy-4-chloro-5-fluoropyrimidine with ammonia to yield 5-fluoro-cytosine.
A process for producing 5-fluorouracil using an aqueous phosphoric acid solution as a solvent which is a good solvent for an intermediate resulting from the reaction between uracil and elemental fluorine, and permits the reaction to proceed smoothly, but which can precipitate the final product, 5-fluorouracil, after cooling the heat-treated reaction solution to room temperature, with no need to evaporate the solvent. The process comprises reacting uracil in an aqueous phosphoric acid solution with elemental fluorine and heating the resultant reaction solution to form 5-fluorouracil.
