Synthesis of functionalized pyridazin-3(2H)-ones via selective bromine-magnesium exchange and lactam directed ortho C-H magnesiation

Tom Verhelst; Jens Maes; Zuming Liu; Sergey Sergeyev; Bert U W Maes

doi:10.1021/jo201009m

Synthesis of functionalized pyridazin-3(2H)-ones via selective bromine-magnesium exchange and lactam directed ortho C-H magnesiation

J Org Chem. 2011 Aug 19;76(16):6670-7. doi: 10.1021/jo201009m. Epub 2011 Jul 20.

Authors

Tom Verhelst¹, Jens Maes, Zuming Liu, Sergey Sergeyev, Bert U W Maes

Affiliation

¹ Organic Synthesis, Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium.

PMID: 21732644
DOI: 10.1021/jo201009m

Abstract

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.