(1-Phenyl-1-tosyl)methyl isocyanide

37643-54-2

36635-66-2

General procedure for the synthesis of 1-((isocyano(phenyl)methyl)sulfonyl)-4-methylbenzene from N-(phenyl(p-toluenesulfonyl)methyl)formamide: N-(α-toluenesulfonylbenzyl)formamide (16.73 g, 57.8 mmol) and anhydrous THF (120 mL) were added to a 500 mL three-necked round-bottom flask equipped with a magnetic stirrer. Phosphoryl chloride (10.78 mL, 116.0 mmol) was added slowly via syringe and the resulting reaction solution was stirred at 25 °C for 5 min. Subsequently, the reaction system was cooled to about 0 °C in an ice/salt bath and triethylamine (48.4 mL, 347.0 mmol) was slowly added through a dropping funnel over 45 min while the reaction temperature was controlled below 10 °C. After the addition of triethylamine, the reaction was continued with stirring at 5-10 °C (ice bath) for 45 min. After completion of the reaction, ethyl acetate (85 mL) and water (85 mL) were added to the system, stirred for 5 min and then transferred to a separatory funnel to separate and discard the aqueous layer. The organic phase was washed sequentially with water (2 x 85 mL), saturated sodium bicarbonate solution (85 mL), and brine (50 mL), and subsequently concentrated under reduced pressure to a slurry residue. The residue was diluted with n-propanol (85 mL) and concentrated to one-half of the original volume, cooled to 0 °C and kept at 0 °C for 15 min to promote crystallization. The resulting solid was collected by filtration through a Brinell funnel, washed with cold n-propanol (2 x 50 mL) and finally dried under vacuum to give α-toluenesulfonylbenzyl isocyanide (7.47 g, 48% yield) as a beige solid.1H NMR (200 MHz, CDCl3) δ 7.60 (d, 2H, J = 8.2 Hz), 7.30-7.52 (m, 5H), and 5.61 (s, 1H), 2.47 (s, 3H).