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Synthesis of Functionalized Pyridazin-3(2H)-ones via Nucleophilic Substitution of Hydrogen (SNH)

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journal contribution
posted on 21.01.2011, 00:00 by Tom Verhelst, Stefan Verbeeck, Oxana Ryabtsova, Stefaan Depraetere, Bert U. W. Maes
Reaction of 2-benzyl-5-halopyridazin-3(2H)-ones (3) with Grignard reagents followed by quenching with electrophiles unexpectedly yielded 4,5-disubstituted pyridazin-3(2H)-ones instead of 5-substituted pyridazin-3(2H)-ones. These reactions represent the first examples of cine substitution in which the anionic σH-adduct is quenched by electrophiles (other than a proton) before elimination takes place. Insight into the reaction mechanism led to the direct transformation of 2-benzylpyridazin-3(2H)-one (7) and 2-benzyl-6-chloropyridazin-3(2H)-one (9) into the corresponding C-4 alkyl and aryl derivatives (when Br2 was used as the electrophile).