Syntheses and Reactions of Pyridazine Derivatives XX. Studies on the Radical Methylation of the 1,2-Diazine System

Protonated pyridazines (1,2,3) on reaction with methyl radical (generated by oxidative decarboxylation of acetic acid or by redox reaction of t-Bu00H/FeS04.7H0) are shown main-2 ly to be attacked at positions 8 to the nitrogen atoms.However, formation of compounds 2,4,5,5,8,9 and 10 indicates lower degree of regio~electivity compared with homolytic benzylation or acylation of the 1.2-diazine system.Synthesis of ethyl 5-styryl-4p y r i d a z i n e c a r b o x y l a t e s l ~, ~) w a s achieved by homolytic methylation of ethyl 4 -p y r i d a z i n e c a r b o ~~l a t e 1 ~1 followed by condensation with aromatic carbaldehydes.In spite of the fact that the 'Minisci" reaction2 has, due to its high selectivity and versatility, attracted much attention in heterocyclic chemistry during the last decade, there are, to our knowledge, only a few reports 3 -1 3 dealing with this type of substitution reactions of the protonated 1.2-diarine system.We describe herein investigations of reactions of protonated pyridazine (1).methylpyridazines 2 and 3 and ethyl 4 -p y r i d a z i n e c a r b o x y l a t e l ~) with methyl radical generated by ~g+-catalyzed oxidative decarboxylation of acetic acid with peroxy-disulphate5 (method A ) or by redox process of ~-B U O O H / F ~S O ~. ~H ~O ' ~ (method Bl, respectively.As can be seen from results listed in Tables 1 and2, reactions of 1.2 and 3 yield,In contrast to findings with photo-induced radical methylation of pyridazines, 6mixtures, containing all of the theoretically possible C-methylated pyridazines.15 compounds 1-10.all known from literature.6,16-21could be separated by means of GLC.They were identified by their behaviour in gas-chromatographic analysis and their spectroscopic Ims, nmr) characteristics.