Synthesis of functionalized pyridazin-3(2H)-ones via nucleophilic substitution of hydrogen (SNH)

Org Lett. 2011 Jan 21;13(2):272-5. doi: 10.1021/ol102703w. Epub 2010 Dec 7.

Abstract

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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Combinatorial Chemistry Techniques
  • Hydrocarbons, Chlorinated / chemical synthesis*
  • Hydrocarbons, Chlorinated / chemistry
  • Hydrogen / chemistry*
  • Molecular Structure
  • Pyridazines / chemical synthesis*
  • Pyridazines / chemistry
  • Stereoisomerism

Substances

  • Hydrocarbons, Chlorinated
  • Pyridazines
  • Hydrogen