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Synthesis of Functionalized Pyridazin-3(2H)-ones via Selective Bromine–Magnesium Exchange and Lactam Directed Ortho C–H Magnesiation

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posted on 19.08.2011, 00:00 authored by Tom Verhelst, Jens Maes, Zuming Liu, Sergey Sergeyev, Bert U. W. Maes
Selective bromine–magnesium exchange on 2-benzyl-5-bromo-4-methoxypyridazin-3(2H)-one could be achieved when MesMgBr was used as reagent. With more nucleophilic RMgCl species (R = Bu, i-Pr, Ph) both nucleophilic addition–elimination at C-4 and bromine–magnesium exchange at C-5 occurred. In 2-benzyl-5-bromopyridazin-3(2H)-one, which does not contain a substituent at C-4, addition could not be suppressed. Less nucleophilic Mg amides (TMPMgCl·LiCl) allowed regioselective C–H magnesiation at the C-4 position in such substrates, as exemplified for 2-benzyl-5-chloro- and 2-benzyl-6-chloropyridazin-3(2H)-one. Quenching of the magnesiated pyridazinones with electrophiles gives access to a variety of hitherto unknown pyridazin-3(2H)-one derivatives.