Potassium tert-Butoxide

Used Chemicals

• Benzyl Alcohol [B2378]
• Benzonitrile [B0082]
• Potassium tert-Butoxide [P1008]
• 1,4-Dioxane

Procedure

To a solution of benzyl alcohol (540 mg, 5.0 mmol), benzonitrile (1.03 g, 10 mmol, 2.0 eq.) in 1,4-dioxane (10 mL) was added potassium tert-butoxide (1.12 g, 10.0 mmol, 2.0 eq.) at r.t. and the mixture was stirred at 130 °C for overnight. The solvent was removed under reduced pressure and the residue was purified by column chromatography (on silica gel, ethyl acetate:hexane = 0:1 - 1:2) several times, giving N-benzylbenzamide as a white solid (513 mg, 49% yield).

Experimenter’s Comments

The reaction mixture was monitored by UPLC.
The reaction was carried out using a pressure-resistant test tube.
Purification by column chromatography was performed several times.

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

• Direct Synthesis of Amides from Benzonitriles and Benzylic Alcohols via a KOt‑Bu-Mediated MPV-type Hydrogen Transfer Process
• G. Li, M. Li, Z. Xia, Z. Tan, W. Deng, C. Fang. J. Org. Chem. 2022, 87, 8884.

References

• 1)Transesterification/Acylation of Secondary Alcohols Mediated by N-Heterocyclic Carbene Catalysts
  • R. Singh, R. M. Kissling, M. Letellier, S. P. Nolan, J. Org. Chem. 2004, 69, 209.
• 2)Protection for the Hydroxyl Group, Including 1,2- and 1,3-Diols
  • P. G. M. Wuts, in Greene’s Protective Groups in Organic Synthesis, 5th ed., ed. by P. G. M. Wuts, John Wiley & Sons, Inc., Hoboken, New Jersey, 2014, Chap. 2, 17.

References

• Potassium tert-Butoxide-Catalyzed Dehydrogenative Si-O Coupling: Reactivity Pattern and Mechanism of an Underappreciated Alcohol Protection
  • A. Weickgenannt, M. Oestreich, Chem. Asian J. 2009, 4, 406.
• Protection for the Hydroxyl Group, Including 1,2- and 1,3-Diols
  • P. G. M. Wuts, in Greene’s Protective Groups in Organic Synthesis, 5th ed., ed. by P. G. M. Wuts, John Wiley & Sons, Inc., Hoboken, New Jersey, 2014, Chap. 2, 17.