Synthesis of 2-Substituted 1-Hydroxyimidazoles through Directed Lithiation.
Benzylation of 3-hydroxyimidazole 1-oxide gave 3-(benzyloxy)imidazole 1-oxide, which was deoxygenated with phosphorous trichloride to produce 1-(benzyloxy)imidazole. 1-(Benzyloxy)imidazole was deprotonated selectively at C-2 by n-butyllithium. The anion formed was reacted with electrophiles to give 1-(benzyloxy)imidazoles with carbon, halogen, silicon, or sulfur substituents at the 2-position. Subsequent debenzylation afforded 2-substituted 1-hydroxyimidazoles which in turn could be deoxygenated to give 2-substituted imidazoles.
Eriksen
Birgitte Langer
BL
Department of Medicinal Chemistry, Royal Danish School of Pharmacy, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
Vedsø
Per
P
Morel
Sandrine
S
Begtrup
Mikael
M