Sulfur Dioxide → 4-(5-Methyl-4-phenylisoxazol-3-yl)benzenesulfonamide

Participants

Reaction Conditions

Reaction Steps

4-[5-Methyl-4-phenylisoxazol-3-yl]bromobenzene from Step 3 (1.73 g, 5.5 mmol) and tetrahydrofuran (100 mL) were stirred at -78° C. under nitrogen. Butyllithium (1.6M in hexanes, 4.1 mL, 6.6 mmol) was added dropwise, maintaining the temperature below -60° C. After stirring at -78° C. for 0.5 hour, sulfur dioxide gas was passed through a stainless steel needle above the surface of the solution. After 1 minute, the solution changed color from orange to clear, and after 10 minutes pH paper indicated an acidic reaction. Gas addition was ceased and the cooling bath was removed. After 1 hour, the mixture was concentrated to 25 mL and hexane (100 mL) was added. A white precipitate formed which was isolated by filtration. This solid was dissolved in water (50 mL) and sodium acetate (4.5 g, 55 mmol), and hydroxylamine-O-sulfonic acid (0.75 g, 6.6 mmol) were added. The resulting mixture was stirred at room temperature overnight and extracted with ethyl acetate (2×50 mL). The combined extract was washed with brine, dried over MgSO4, and concentrated. A white solid was recrystallized from dichloromethane/hexane (0.8 g, 46%): mp 150.9°-152.3° C. 1H NMR (acetone-d6 /300 MHz) 7.9 (d, J=9.7 Hz, 2H), 7.6 (d, J=9.7 Hz, 2H), 7.4 (m, 3H), 7.3 (m, 2H), 6.7 (bs, 2H), 2.5 (s, 3H). Anal. Calc'd. for C16H14N2O3S: C, 61.13; H, 4.49; N, 8.91. Found: C, 61.18; H, 4.52; N, 8.85. High resolution mass spectrum calc'd. (M+H): 315.0803. Found : 315.0793.

Provenance & Evidence