Water → 4-Bromo-5-fluoro-2-nitroaniline

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([C:6]([N+:9]([O-:11])=[O:10])=[CH:7][CH:8]=1)[NH2:5].[Br:12]N1C(=O)CCC1=O.O>CN(C=O)C>[Br:12][C:8]1[CH:7]=[C:6]([N+:9]([O-:11])=[O:10])[C:4]([NH2:5])=[CH:3][C:2]=1[F:1]

Participants

Procedure

4-Bromo-3-fluoro-6-nitroaniline was prepared using an adaptation of the method of Mitchell et al. (Mitchell, R. H. et al., J. Org. Chem. 44:4733 (1979)). To a solution of 3-fluoro-6-nitroaniline (500 mg, 3.2 mmol) in dry DMF (15 mL) under N2 was added dropwise a solution of N-bromosuccinimide (626 mg, 3.2 mmol) in dry DMF. The reaction was allowed to stir 48 h. The solution was then poured into 100 mL H2O. The cloudy yellow suspension which formed was then extracted with 4×25 mL of methylene chloride. The combined organic extracts were washed with 4×25 mL of H2O and 25 mL sat'd NaCl solution. The organic phase was dried (MgSO4) and the drying agent removed by vacuum filtration. The solvent was rotary evaporated to yield a yellow orange oil which crystallized on standing. 1H NMR showed this solid to be a mixture of mono- and dibrominated products in a 3.8:1 ratio. The mixture was separated by flash chromatography (2:1 hexanes:ethyl acetate) to yield 324 mg of a yellow solid (43%). 1H NMR (CDCl3) δ6.19(br s, 2H, NH2); 6.58(d, 1H, JHF =9.6, ArH); 8.39(d, 1H, JHF =6.9, ArH).