Hydrochloric Acid → 2-Nitro-4-trifluoromethylanisole

Participants

Reaction Conditions

Reaction Steps

Sodium methoxide (1.35 g; 25 mmol; 2.5 equiv) was slurried in DMSO (10 mL) and cooled in a cool water bath. Nitroethane (0.79 mL; 11 mmol; 1.1 equiv.) and 4-chloro-3-nitrobenzotrifluoride (1; 1.49 mL; 10 mmol) were mixed and added slowly dropwise with cooling such that the temperature remained between 15 and 20° C. After the addition was complete, the reaction mixture was allowed to warm slowly over 3 h from 15 to 18° C. and then stirred overnight at 18° C. to completely consume 1 according to GC analysis. Toluene (10 mL) was added and the mixture was cooled in ice water and 3 N HCl (10 mL; 30 mmol; 3 equiv) was added dropwise such that the temperature remained below 20° C. After the addition the layers were separated, and the organic solution was dried (Na2SO4) and concentrated to afford 2.60 g of crude product. Analysis of this material by 1H NMR and GC indicated that the major product was 6 with 2 and 3 as minor products. 6: 1H NMR (CDCl3) δ 8.127 (d, 1H, J=1.8 Hz); 7.803 (dd, 1 H, J=2.1, 8.7 Hz); 7.203 (d, 1H, J=9.06 Hz); 4.028 (s, 3H). GC (30 m DB-17, 100° C., 3 min; 100-280° C., 15°/min); 280° C., 1 min): tR 9.35 min.

Provenance & Evidence