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TCI Practical Example: Condensation Reaction Utilizing the Boronic Acid Catalyst

We are proud to introduce the condensation reaction of benzoic acid and benzylamine using 2,4-bis(trifluoromethyl)phenylboronic acid as a catalyst. The reaction produces water only as a by-product. The catalyst can be removed by a partition with basic water solution.

Used Chemicals

• Benzoic Acid [B2635]
• Benzylamine [B0406]
• 2,4-Bis(trifluoromethyl)phenylboronic Acid [B3022]
• Fluorobenzene [F0034]

Procedure

To a solution of benzoic acid (122 mg, 1.0 mmol) and benzylamine (107 mg, 1.0 mmol) in fluorobenzene (5 mL) was added molecular sieves 3A (2 g) at room temperature. After that 2,4-bis(trifluoromethyl)phenylboronic acid (13 mg, 0.05 mmol) was added to the reaction mixture and stirred at reflux temperature for 24 hours. The reaction mixture was filtered on celite pad and washed with EtOAc. The filtrate was washed with 2 mol/L HCl aq. (30 mL), saturated NaHCO₃ aq. (30 mL), and brine (30 mL), dried over sodium sulfate and filtered. The solvent was removed under reduced pressure to give N-benzylbenzamide as a white solid (135 mg, 64% yield).

Experimenter’s Comments

The reaction mixture was monitored by LC.

Analytical Data

N-benzylbenzamide

¹H NMR (270 MHz, DMSO-d6); δ 9.05 (brt, 1H, J = 5.4 Hz), 7.90 (dd, 1H, J = 7.3, 1.6 Hz), 7.56-7.44 (m, 3H), 7.36-7.32 (m, 4H), 7.25 (q, 1H, J = 7.3 Hz).

Lead Reference

• The ortho-substituent on 2,4-bis(trifluoromethyl)phenylboronic acid catalyzed dehydrative condensation between carboxylic acids and amines
• • K. Wang, Y. Lu, K. Ishihara, Chem. Commun. 2018, 54, 5410.