General procedure for the synthesis of 2-fluoro-6-nitrobenzaldehyde from 2-fluoro-6-nitrotoluene and N,N-dimethylformamide dimethyl acetal: A mixture of 2-fluoro-6-nitrotoluene and N,N-dimethylformamide dimethyl acetal (2.75 eq.) was heated to 135 °C and kept for 12 hours. Upon completion of the reaction, the reaction mixture was cooled to room temperature and slowly added dropwise to a pre-prepared water/DMF (1:1, 1.1 M) solution of NaIO4 (2.75 equiv.). After the dropwise addition, the reaction mixture was stirred at room temperature for 3 hours. Subsequently, the reaction mixture was filtered and the solid was washed with toluene. The filtrate was transferred to a partition funnel to separate the organic and aqueous layers. The organic layer was washed with water and dried with anhydrous Na2SO4. The solvent was removed by evaporation under reduced pressure to give the crude product. The crude product was purified by rapid chromatography on silica gel with gradient elution using EtOAc/petroleum ether (1:30) as eluent to finally obtain 2-fluoro-6-nitrobenzaldehyde in 23% yield. Mass spectrometry analysis (ES+): the theoretical value of C7H4FNO3 was 169 and the measured value was 170 (M+H)+.
