4-Amino-2-iodobenzonitrile 98

• Hydroamination-double hydroarylation for synthesis of fuzed carbazoles
• Cycloisomerizations of aromatic homo- and bis-homopropargylic amine / amide intermediates
• Asymmetric organocatalytic condensation and cycloaddition
• Regioselective aryl C-H bond functionalization
• Synthesis of [(triisopropylsilyl)ethynyl]indole derivatives
• Domino condensation / S-arylation / heterocyclization reactions

873-74-5

33348-34-4

General procedure for the synthesis of 4-amino-3-iodobenzonitrile from 4-aminobenzonitrile: To a methanol (30 mL) solution of 4-aminobenzonitrile (2.4 g, 20 mmol) and 30% H2O2 (not titrated prior to use), a methanol (50 mL) solution of iodine (5.05 g, 12 mmol) was added at room temperature. The reaction mixture was stirred at room temperature for 48 hours, during which time it was replenished daily with fresh H2O2 (2 mL). Upon completion of the reaction, the mixture was concentrated under reduced pressure and treated with saturated Na2S2O3 solution until most of the color disappeared. The precipitated solid was collected by filtration, and the filtrate was diluted to 300 mL with ethyl acetate, washed sequentially with saturated aqueous NaHCO3 solution, brine, and dried with anhydrous MgSO4. After filtration, the filtrate was concentrated to dryness under reduced pressure. The crude product was initially purified by crystallization from ethanol to give 4-amino-3-iodobenzonitrile (3 g). The residue was further recrystallized from dichloromethane/hexane mixed solvent to give additional 4-amino-3-iodobenzonitrile (1.4 g). The total yield was 4.4 g (88%). The structure of the product was confirmed by 1H NMR (CDCl3): δ 7.87 (d, 1H, J = 1.8 Hz), 7.37 (dd, 1H, J = 1.8, 8.4 Hz), 6.68 (d, 1H, J = 8.4 Hz), 4.62 (br s, 2H).