Nitric Acid → 2-Bromo-4-methoxy-1-nitrobenzene

Participants

Reaction Conditions

Reaction Steps

Nitric acid (70%, 5 mL) was placed in a 25 mL round-bottomed flask. Concentrated sulphuric acid (4 mL) was then added dropwise with stirring. The mixture was kept cool during the addition by immersing the flask in an ice bath. 3-Methoxybromobenzene (4 g, 21.5 mmol) was then introduced dropwise. The reaction mixture was then heated to 50° C. and stirred for 5 h. After cooling, the mixture was poured into 100 mL of cold water and extracted with ethyl acetate (30 mL×3). The organic layers were combined and washed with water (50 mL×4) and brine. The ethyl acetate layer was dried with anhydrous sodium sulfate and concentrated in vacuo. The crude product was purified by column chromatography on silica gel using 95:5 hexanes:ethyl acetate. The first compound that eluted from the column was 3-methoxy-4-nitrobromobenzene (1.2 g) in 24% yield; 1H NMR (CDCl3) δ3.96(3H, s), 7.17 (1H, dd, J1=8.6, J2=1.9), 7.24 (1H, d, J=1.9), 7.75 (1H, d, J=8.6); 13C NMR δ57.34 117.58, 124.00, 127.41, 129.05, 142.26, 154.02. The second compound eluting from the column was 24 (1.5 g, 30% yield); 43-45° C.; 1H NMR (CDCl3) δ3.89 (3H, s), 6.91 (1H, dd, J1=9.1, J2=2.7), 7.21 (1H, d, J=2.7), 7.98 (1H, d, J=9.1); 13C NMR δ56.68, 114.02, 117.29, 120.61, 128.46, 163.23.

Provenance & Evidence