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TCI Practical Example: Sandmeyer Reaction Using tBuONO

We are proud to present the preparation of diazonium salt by using tBuONO followed by the Sandmeyer reaction to introduce the iodo group.

Used Chemicals

• p-Anisidine [A0487]
• p-Toluenesulfonic Acid Monohydrate (=p-TsOH·H₂O) [T0267]
• Potassium Iodide [P1721]
• tert-Butyl Nitrite (= tBuONO) [N0357]
• Acetonitrile

Procedure

tert-Butyl nitrite (0.30 mL, 2.5 mmol, 2.5 eq.) was added dropwise to a solution of p-anisidine (123 mg, 1.0 mmol), p-toluenesulfonic acid monohydrate (190 mg, 1.0 mmol, 1.0 eq.) and potassium iodide (415 mg, 2.5 mmol, 2.5 eq.) in acetonitrile (5 mL) at 0 °C. The mixture was stirred at same temperature for 30 minutes. Then the reaction mixture was heated to 60 °C and stirred for 4 hours. After quenching with water (15 mL), the mixture was extracted with ethyl acetate (15 mL x 3) and the 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 filtrate 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 red solid (202 mg, 86% yield).

Experimenter's Comments

The reaction mixture was monitored by UPLC.

Analytical Data

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).

Lead Reference

• 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. Filimonova, P. Knochel, Synthesis 2007, 81.