Process for the preparation of 5-acylpyrimidines

Claim 1

A process for the preparation of a 5-acylpyrimidine of the formula ##STR46## in which R represents straight-chain or branched alkyl with 1 to 12 carbon atoms, straight-chain or branched alkenyl with 3 to 6 carbon atoms, straight-chain or branched alkinyl with 3 to 6 carbon atoms or cycloalkyl and cycloalkylalkyl with in each case 3 to 7 carbon atoms in the alkyl part and in each case optionally mon-, di- or tri-substituted by identical or different alkyl substituents with 1 to 4 carbon atoms; or represents phenyl which is optionally mono-, di- or tri-substituted by identical or different substituents selected from the group consisting of halogen, hydroxyl, alkyl, alkoxy and alkylthio with in each case 1 to 4 carbon atoms; halogenoalkyl, halognoalkoxy and halogenoalkylthio with in each case 1 to 4 carbon atoms and 1 to 5 identical or different halogen atoms; nitro, cyano and alkoxycarbonyl with 1 to 4 carbon atoms in the alkoxy part, and phenyl and phenoxy, in each case optionally substituted by halogen; or furthermore represents 5- to 6-membered heteroaryl which has 1 to 3 oxygen, nitrogen and/or sulphur atoms, and is optionally mono-, di or tri-substituted by identical or different substitutents, possible substituents being the abovementioned substituents on phenyl, or represents the groupings ##STR47## wherein R 3 represents fluorine, chlorine or bromine; R 4 represents hydrogen, fluorine, chlorine or bromine; R 5 represents straight-chain or branched alkenyl with 2 to 4 carbon atoms, straight-chain or branched alkinyl with 3 to 5 carbon atoms, or the CHO group, alkoximinomethyl with 1 to 4 carbon atoms in each alkoxy part, dialkoxymethyl with 1 to 4 carbon atoms in each alkoxy part, dioxolanyl and dioxanyl; R 6 represents cyano, or represents phenyl which is optionally mono- di or tri-substituted by identical or different substituents, possible substituents being the substituents on phenyl which have already been mentioned above, or represents the groupings --XR 7 and --CONR 8 R 9 , wherein R 7 represents straight-chain or branched alkyl with 1 to 6 carbon atoms or halogenoalkyl with 1 to 4 carbon atoms and 1 to 5 identical or different halogen atoms or represents phenyl or phenylalkyl, with 1 or 2 carbon atoms in the alkyl part, each of which is optionally mono-, di- or tri-substituted by identical or different substituents, possible substituents in each case being the substituents on phenyl which have already been mentioned above; R 8 represents hydrogen or straight-chain or branched alkyl with 1 to 4 carbon atoms, or represents phenyl which is optionally mono- di- or tri-substituted by identical or different substituents, possible substituents being the substituents on phenyl which have already been mentioned above; R 9 represents hydrogen or straight-chain or branched alkyl with 1 to 4 carbon atoms; x represents oxygen or sulphur and n represents the number 0, 1 or 2, comprising reacting a methyl ketone of the formula R--CO--CH.sub.3 (a) in a first stage with a formylating reagent selected from the group consisting of a formic acid alkyl ester with 1 to 4 carbon atoms in the alkyl group, and phenyl formate, in the presence of a base at a temperature between -25° C. and +60° C., thereby forming an enol-ketone of the formula R--CO--CH═CH--OR.sup.10 in which R 10 represents hydrogen or an alkali metal, in a second stage reacting the enol-lactone with formamidine or a salt thereof with an organic or inorganic acid, at a temperature between -25° C. and +50° C. thereby to form a formamidine derivative of the formula R--CO--CH.sub.2 --CH═N--CH═NH; in a third state reacting the formamidine derivative with an amino-formylating agent selected from the group consisting of (α) a formamidine acetal of the formula ##STR48## in which R 12 and R 13 independently of one another represent metyl, ethyl, n-propyl, isopropyl or n-butyl, or R 12 and R 13 , together With the nitrogen atom to which they are bonded, represent pyrrolidinyl, piperidinyl, morpholinyl or N-methyl-piperazinyl, and R 14 represents methyl, ethyl or n-propyl, (β) an aminal ester of the formula R.sup.14 --O--CH(NR.sup.12 R.sup.13).sub.2 and (γ) a formimimum halide of the formula ##STR49## in which Hal represents halogen, at a temperature between -25° C. and +50° C., thereby to form a compound of the formula ##STR50## and, in a fourth stage cyclizing such compound by heating to a temperature between 0° C. and 100° C., or (b) in a first stage with a formylating reagent selected from the group consisting of a formic acid alkyl ester with 1 to 4 carbon atoms in the alkyl group, and phenyl formate, in the presence of a base at a temperature between -25° C. and +60° C., to form an enol-ketone of the formula R--CO--CH═CH--OH, in a second stage reacting the enol-lactone with an amino-formylating agent selected from the group consisting of (α) a formamidine acetal of the formula ##STR51## (β) an amimal ester of the formula R.sup.14 --O--CH(NR.sup.12 R.sup.13).sub.2 and (γ) a formiminum halide of the formula ##STR52## at a temperature between -25° C. and +50° C., to form a compound of the formula ##STR53## reacting such compound with formamidine at a temperature between -20° C. and +30° C., and then cyclizing the product formed by heating to a temperature between 0° C. and 100° C.