TCI Practical Example: Dehydration Reaction of an Amide by Using Cyanuric Chloride

We are proud to present the synthesis of 4-bromobenzonitrile by the dehydration of 4-bromobenzamide by using cyanuric chloride.

Used Chemicals

• Cyanuric Chloride [C0460]
• 4-Bromobenzamide [B4216]
• DMF

Procedure

Cyanuric chloride (183 mg, 1.0 mmol, 0.67 eq.) was added to a solution of 4-bromobenzamide (300 mg, 1.5 mmol) in DMF (3 mL) at 0 °C. The mixture was stirred at room temperature for 3.5 hours and quenched with water (15 mL). The solution was extracted with ethyl acetate (15 mL x 3) and the organic layer was washed with 2 mol/L HCl (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-bromobenzonitrile as a pale white solid (260 mg, 95% yield).

Experimenter's Comments

The reaction mixture was monitored by UPLC.

Analytical Data

4-bromobenzonitrile

¹H NMR (400 MHz, CDCl₃); δ 7.64 (d, 2H, J = 8.4 Hz), 7.53 (d, 2H, J = 8.4 Hz).

Lead Reference

• (S)-5-Pyrrolidin-2-yl-1H-Tetrazole
  • V. Aureggi, V. Franckevicius, M. O. Kitching, S. V. Ley, D. A. Longbottom, A. J. Oelke, G. Sedelmeier, Org. Synth. 2008, 85, 72.