Synthesis of functionalized pyridazin-3(2H)-ones via nucleophilic substitution of hydrogen (SNH).
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 σ(H)-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 Br(2) was used as the electrophile).
Organic Synthesis, Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium.
Tom
T
Verhelst
Stefan
S
Verbeeck
Oxana
O
Ryabtsova
Stefaan
S
Depraetere
Bert U W
BU
Maes
D020650:Combinatorial Chemistry Techniques; D006843:Hydrocarbons, Chlorinated / Q000138:chemical synthesis* / Q000737:chemistry; D006859:Hydrogen / Q000737:chemistry*; D015394:Molecular Structure; D011724:Pyridazines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D006843:Hydrocarbons, Chlorinated; D011724:Pyridazines; D006859:Hydrogen