Sodium Nitrite

• p-Anisidine [A0487]
• p-Toluenesulfonic Acid Monohydrate (= p-TsOH·H₂O) [T0267]
• Potassium Iodide [P1721]
• Sodium Nitrite [S0565]
• Acetonitrile

Potassium iodide (415 mg, 2.5 mmol, 2.5 eq.) and sodium nitrite (172 mg, 2.5 mmol, 2.5 eq.) in water (5 mL) were added dropwise to the solution of p-anisidine (123 mg, 1.0 mmol) and p-TsOH·H₂O (190 mg, 1.0 mmol, 1.0 eq.) in acetonitrile (10 mL) at 0 °C. The mixture was stirred at room temperature for 2 hours. The reaction was quenched with 10% Na₂S₂O₃ aq. (15 mL) and the aqueous layer was extracted with ethyl acetate (15 mL x 3). The combined organic layer was washed with 2 mol/L HCl aq. (15 mL), sat. NaHCO₃ aq. (15 mL), and brine (15 mL), dried over sodium sulfate and filtered. The solvent was removed under reduced pressure and the residue was purified by column chromatography (on silica gel, ethyl acetate:hexane = 1:4) to give 4-iodoanisole as a pale red solid (154 mg, 66% yield).

The reaction mixture was monitored by UPLC.

4-iodoanisole

¹H NMR (400 MHz, CDCl₃); δ 7.56 (d, J = 8.0 Hz, 2H), 6.68 (d, J = 8.0 Hz, 2H), 3.78 (s, 3H).

• A New, One-Step, Effective Protocol for the Iodination of Aromatic and Heterocyclic Compounds via Aprotic Diazotization of Amines
• E. A. Krasnokutskaya, N. I. Semenischeva, V. D. Filimonov, P. Knochel, Synthesis 2007, 81.