Dimethylformamide → 2-Formyl-3-(4-methylphenyl)pyrrole

Participants

Reaction Steps

Following a standard procedure (Balasubramanian, T. et al., J. Org. Chem. 2000, 65, 7919-7929), a solution of 7 (472 mg, 3.00 mmol) in DMF (0.96 mL) and CH2Cl2 (30 mL) under argon was cooled to 0° C. and then POCl3 (340 μL, 3.60 mmol) was added dropwise. After 1 h, the flask was warmed to room temperature and stirred overnight (˜18 h). The reaction was quenched at 0° C. with 2.5 M NaOH (25 mL). The mixture was poured into water (50 mL), extracted with CH2Cl2, and the combined organic layers were washed with water, brine, dried (Na2SO4), and concentrated. The residue was chromatographed [silica, CH2Cl2/ethyl acetate (9:1)] to give a brown solid. 1H NMR spectroscopy showed two regioisomers in ˜13:1 ratio. Cooling of the solution (ethyl acetate/hexanes) at ˜−16° C. resulted in precipitation of an orange solid, which proved to be a single regioisomer (354 mg, 64%): mp 149-150° C.; 1H NMR δ 2.41 (s, 3H), 6.42-6.44 (m, 1H), 7.10-7.13 (m, 1H), 7.26 (d, J=8.0 Hz, 2H), 7.40 (d, J=8.0 Hz, 2H), 9.63-9.64 (m, 1H), 9.52-9.78 (br, 1H); 13C NMR δ 21.4, 111.6, 126.2, 128.9, 129.3, 129.7, 130.9, 137.7, 137.9, 180.2; FAB-MS obsd 186.0907, calcd 186.0919 (C12H11NO).

Provenance & Evidence