4-Hydroxy-3-nitrobenzonitrile

• 3-azido-4-methoxybenzonitrile
• 4-methoxy-3-nitrobenzonitrile
• ethyl [2,2-dimethyl-6-(Δ²-thiazolin-2-yl)-4H-l,4-benzoxazin-3-one-4-yl]butyrate

3011-34-5

3272-08-0

General procedure for the synthesis of 4-hydroxy-3-nitrobenzonitrile from 4-hydroxy-3-nitrobenzaldehyde: Aromatic aldehyde 1 (0.500 mmol, 1.0 eq.) and trimethylsilyl azide (TMSN3; 115 mg, 1.00 mmol, 2.0 eq.) were dissolved in a pre-mixed solvent mixture of hexafluoroisopropanol (HFIP) and acetonitrile (ACN) (2.0 mL, 1:1 volume ratio) in two dram vials, which was carried out under nitrogen protection. Subsequently, trifluoromethanesulfonic acid (TfOH; 17.7 μL, 0.200 mmol, 0.40 eq.) was added to the reaction system, and exothermic and rapid foaming phenomena due to gas production were immediately observed. The vial was quickly capped and the reaction mixture was stirred at room temperature for 20 to 75 min. Upon completion of the reaction, the reaction mixture was concentrated under a stream of nitrogen. The residue obtained was suspended in a solvent mixture of dichloromethane (CH2Cl2) and hexane and this suspension was upsampled into a cartridge containing 5 g silica gel. Purification was carried out by normal-phase silica gel fast column chromatography using a CombiFlash purification system, and suitable fractions were collected and concentrated to give the target product, aromatic nitrile 2.