DE912094C - Process for the preparation of pyrimidine derivatives - Google Patents

Description

Process for the preparation of pyrimidine derivatives The invention relates to relate to a process for the production of new pyrimidine derivatives, the anticonvulsant Possess properties.

According to the invention there is provided a process for the preparation of pyrimidine derivatives of the formula proposed in which R1 is a one-membered carbocyclic radical, R $ is an alkyl radical with a maximum of 3 carbon atoms and R is a hydrogen atom or an alkyl radical with a maximum of 4 carbon atoms, which is characterized in that a malondiamide derivative of the general formula where R1, R $ and Ra have the meaning given above, or compounds which form such malondiamide derivatives under the reaction conditions are reacted with formic acid or a compound which delivers this under the reaction conditions at a temperature above 150 ° and advantageously in a solvent or diluent .

The reaction can be suitably carried out by the Reaction components together in solution in a solution or Thinners are heated. Such a solvent or diluent can e.g. B. cyclohexanol, methylcyclohexanol, N-methylformamide, N ethylformamide, Dimethylformamide, formanilide, N-methylformanilide, N-phenylformanilide, nitrobenzene, Dichlorobenzenes and monochloronaphthalenes.

A substance can also be used in place of the malondiamide derivative from which the malondiamide derivative is formed in the reaction mixture. Such Substances are e.g. B. the N-methylol and N-formyl derivatives of the malondiamide derivative.

Likewise, a substance can be used in place of formic acid from which formic acid is formed in the reaction mixture. Such substances are z. B. oxalic acid and oxalic acid in the presence of glycerol.

The pyrimidine derivatives prepared according to the process of the present invention are already described in the patent 843 413 and are called antispasmodic Funds used.

The invention is illustrated in the following examples. The parts are parts by weight. EXAMPLE i 11.7 parts of a-phenyl-a-ethyl-N-ethylmalondiamide and 7 parts of 98% aqueous formic acid are heated together for 4 hours to 25o to 26o °, while 39 parts of formic acid are slowly added. The mixture is cooled, washed with water and recrystallized from aqueous methanol and gives 5-phenyl-i, 5-diethylhexahydropyrimidine-4,6-dione with a melting point of 135 ° to 136 °.

In a similar way, 5-phenyl-5-methylhexahydropyrimidine-4, 6-dione (melting point 295 to 296 °), 5-phenyl-5-ethyl-hexahydropyrimidine-4, 6-dione (melting point 281 °), 5-phenyl- 5-ethyl-i-methylhexahydropyrimidine-4, 6-dione (melting point 185 to 186 °), 5-phenyl-5-ethyl-in-propylhexahydropyrimidine-4, 6-dione (melting point 124 to 125 °) and 5-phenyl 5-ethyl-in-butyl-hexahydropyrimidine-4, 6-dione with a melting point of 116 ° can be obtained. The a-phenyl-a-ethereal-Nn-butylmalondiamide, from which this last substance is obtained, has a melting point of 123 ° and is obtained by hydrolysis of the a-phenyl-a-cyano-Nn-butylbutyramide with a boiling point of 196 ° 16 mm print obtained with cold concentrated sulfuric acid. formanilide, N-phenylformanilide, nitrobenzene, dichlorobenzene and monochloronaphthalenes are mentioned.

Example 3 To 22.4 parts of α-phenyl-α-ethylmalondiamide which has been heated to igo °, 27 parts of oxalic acid are added in 15 minutes, and heating is then continued for g hours. The mixture is cooled and diluted with 25 parts of methanol and filtered. 5-Phenyl-5-ethyl-hexahydropyrimidine-4, 6-dione is obtained as the solid residue (melting point 28 °). Example 4 5 parts of the N, N'-dimethylol derivative of a-phenyla-ethylmalondiamide are dissolved in 150 parts of dimethylformamide and the solution is heated on the reflux condenser. 6 parts of 98% aqueous formic acid are then added to the mixture at a rate of 1 part every 30 minutes. 100 parts of dimethylformamide are then distilled from the mixture, which is then cooled and filtered. The solid residue consists of 5-phenyl-5-ethylhexahydropyrimidine-4, 6-dione (melting point 281 °).

The N, N'-dimethylol derivative of a-phenyl-a-äthylmalondiamids with a Melting point of igi ° can be obtained by heating an aqueous suspension of a-phenyl-a-ethylmalondiamide with far more than 2 moles of formaldehyde in the presence of a small amount of potassium carbonate can be obtained. Example 5 2 parts of a-phenyl-a-ethyl-N-formylmalondiamide, 150 parts Dimethylformamide and 10 parts of 98% aqueous formic acid are dissolved together Heated 18o ° for 2 hours and during this time a further 40 parts of formic acid were added. The mixture is distilled to a small volume, cooled and filtered. Of the solid residue consists of 5-phenyl-5-ethylhexahydropyrimidine-4, 6-dione (melting point 281 °).

The a-phenyl-a-ethylformylmalondiamide with a melting point of 170 ° can by oxidation of the N, N'-dimethylol derivative of a-phenyl-a-ethylmalondiamide can be obtained with chromic acid.

Claims (1)

PATENT CLAIMS: Example 2 22.4 parts of a-phenyl-a-ethylmalondiamide and 20 parts of methylcyclohexanol are heated to 180 ° and 28 parts of 85% formic acid are added below the surface of the mixture in 5 hours. The heating to 180 ° is then continued for a further 4 hours. The mixture is cooled, diluted with methanol and filtered. The solid residue consists of 5-phenyl-5-ethylhexahydropyrimidine-4, 6-dione (melting point 281 °). Other solvents that can be used in place of methylcyclohexanol in this example are N-methylformamide, N-ethylformamide, dimethylformamide, formanilide, N-methyli. Process for the preparation of pyrimidine derivatives of the general formula where Rl denotes a one-membered carbocyclic radical, R2 denotes an alkyl group with a maximum of 3 carbon atoms and R3 denotes a hydrogen atom or an alkyl group with a maximum of 4 carbon atoms, characterized in that a malondiamide derivative of the general formula wherein R1, R2 and R3 have the meaning given above or compounds which form such malondiamide derivatives under the reaction conditions are reacted with formic acid or a compound which delivers this under the reaction conditions at a temperature above 150 ° and advantageously in a solvent or diluent. a. Process according to Claim i, characterized in that an N-methylol or N-formyl derivative of the malondiamide derivative of the composition specified in Claim i is used as the condensation partner. 3. The method according to claim i, characterized in that instead of formic acid oxalic acid, optionally together with glycerol, is used as a condensation partner.