Heteroaromatic oxidation pyrimidine

The 2-methyl group of 2-methyl-4-oxo-4//-pyrido[l,2-a]pyrimidines (41) and their 6,7,8,9-tetrahydro derivatives can be condensed with aromatic and heteroaromatic aldehydes in the presence of methanolic sodium metho-oxide.57 60 292... 

Sulfotransferase activity is not restricted to minoxidil. The ability of other pyrimidine-, as well as pyridine-, triazine- and imidazole N-oxides to serve as substrates was investigated using soluble liver preparation and PAPS. The variety of structures studied indicated that heteroaromatic N-oxides are generally metabolized by sulfotransferases183. Presumably, all of the heterocycles tested were conjugated via their N-oxide oxygens. 

Certain heteroaromatic compounds that have acidic methyl groups are effective in the Knoevenagel condensation. 6-Methyl-1,3,5-triazine (156), 2-methylpyridine V-oxides (157), quinolines and pyrimidines all condense with aromatic aldehydes in the presence of the usual catalysts. An example of a doubly activated methylene compound in which one activation group is a heterocycle is the 2-oxopro-pylthiazole (158), which condenses with a number of aldehydes. " ... 

JV-Oxide rearrangements in heteroaromatic compounds are frequently induced by either photochemical or acid anhydride initiated processes, and usually involve formation of a C—O bond at the carbon a to the original N-oxide. 60 One of the few -rearrangements is observed by treating 1,3-dimethylpyrido[2,3-r/Jpyrimidine-2,4(l //,3//)-dione 8-oxide (1 see Section 7.2.2.1.1.5.1.) with acetic acid/acetic anhydride at 90 CC, which gives 6-acetoxy-l,3-dimethylpyrido[2,3-t/]pyrimidine-2,4(l//,3//)-dione (2). When the reaction is run at reflux temperature in trifluoroacctic anhydride/trifluoroacetic acid, a 46% yield each of the a- and -product, 3 and 4, respectively, is obtained.310... 

The SNAr reactions of heteroarenes can be realized in a similar manner, as in the series of arenes [71, 82]. These nucleophilic reactions are analogous to electrochemical Sn transformations of arenes [22, 24, 25]. Terrier and co-workers considered an opportunity for electrochemical methoxylation of 4,6-dinitrobenzofuroxan by action of the methoxide ion via the SnAt mechanism [21]. The intermediate o -complex formed was oxidized successfully into the corresponding substitution product. Analogously, the formation of heteroaromatic amines has been suggested to occur via intermediacy of the corresponding amino adducts, as exemplified by the oxidation of the o -complex derived fi om the reaction of pyrimidine with NH2 (Scheme 26) [3, 102-104]. 

The synthesis of Primisulfuron-methyl (299) started from reaction of diethyl malonate and thiourea (Scheme 77) [284]. The resulting pyrimidine derivative 348 was methylated, difluoromethylated and then oxidized to give sulfone 351. Reaction of 351 with aqueous ammonia gave heteroaromatic amine 352, which was transformed to Primisulfuron-methyl (299) upon treatment with isocyanate 353. 

---