2,6-Lutidine → 2-Amino-4-bromobenzonitrile

Participants

Reaction Steps

To a cold solution of oxime (10) (8 g, 33.33 mmol) in CH2Cl2 (200 mL) at 0° C. was added 2,6-lutidine (4.5 mL, 38.7 mmol), followed by the dropwise addition of triflouromethanesulfonic anhydride (5.6 mL, 33.33 mmol). The cooling bath was removed, and the mixture was heated to reflux for 3 h. The reaction mixture was cooled to room temperature, and DBU (9.9 mL, 66.66 mmol) was added dropwise while maintaining the internal temperature of the reaction below 30° C. The mixture was further stirred at room temperature for 1 h and poured with vigorous stirring into excess dilute NaHCO3. This mixture was then stirred for several minutes, and the organic layer was separated. The aqueous layer was re-extracted with CH2Cl2 (100 mL×2). The combined extracts were dried with MgSO4 and concentrated to leave a dark brown solid, which was passed through a short silica column, eluting with CH2Cl2 (100%). The resulting fraction was dried under vacuum, triturated with CH2Cl2/hexanes, and the solid formed was filtered and dried under vacuum to afford 5.36 g (82%) of 11 as a light yellow solid. IR (KBr) νmax. cm−1: 3436, 3310 (NH2), 3032 (Ar—H), 2920 (Alph-H), 2246 (CN), 1610, 1512, 1418 (C═C). 1H NMR (500 MHz, CDCl3) δ=4.47 (br. s, 2H, NH2); 6.88 (dd, 1H, J=2.8, 8.2 Hz, H-5); 6.94 (br. s, 1H, H-3); 7.24 (d, 1H, J=8.2 Hz, H-6); 13C NMR (125.7 MHz, CDCl3) δ=95.17 (C-1), 117.16 (CN), 118.15 (C-3), 121.60 (C-5), 129.03 (C-4), 133.60 (C-6), 150.47 (C-2). Calculated (%) for C7H5BrN2 (195.96); C: 42.67, H: 2.56, N: 14.22. found (%); C: 42.60, H: 2.61, N: 14.17.

Provenance & Evidence