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DOI: 10.1055/s-2005-868523
First Halogen Dance Reaction on Oxazoles. Synthesis of 4,5-Disubstituted 2-Phenyloxazoles
Publication History
Publication Date:
02 May 2005 (online)
Abstract
The halogen dance reaction was investigated on the oxazole system for the first time. Various 5-substituted 4-bromo-2-phenyloxazole derivatives are accessible via this convenient methodology.
Key words
halogen dance - metalation - lithiation - oxazole
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References
General Procedure for the Halogen Dance Reaction: A freshly prepared solution of LDA (1.5 equiv) in anhyd THF (10 mL) was added to a solution of 5-bromo-2-phenyloxazole (1; 1 equiv) in anhyd THF at -80 °C under nitrogen. The reaction was monitored by TLC, once the reaction had reached completion (after 15-30 min,) the corresponding electrophile (1.5 equiv in 5 mL anhyd THF) was added and the reaction was allowed to warm to 0 °C over 1 h. Water was added to this solution and 2/3 of the THF was removed under reduced pressure. The mixture was extracted with CH2Cl2 and washed with sat. NaHCO3 and brine. The organic layer was dried over Na2SO4, filtered and the solvent was removed under reduced pressure. The crude product was purified by column chromatography.
15(4-Bromo-2-phenyloxazol-5-yl)phenylmethanol ( 6b): Beige crystals (78%); mp 116-119 °C; 1H NMR (CDCl3): δ = 3.15 (br s, 1 H, OH), 6.00 (s, 1 H, CH), 7.20-7.56 (m, 8 H, H3′, H4′, H5′, 5H′′), 7.84-7.99 (m, 2 H, H2′, H6′); 13C NMR (CDCl3): δ = 67.0 (d, CHOH), 114.7 (s, C4), 126.2 (d, CH), 126.3 (s, C1′), 126.5 (d, CH), 128.4 (d, C4′), 128.5 (d, CH), 128.5 (d, CH), 131.1 (d, C4′′), 139.4 (s, C1′′), 148.3 (s, C5), 161.4 (s, C2).