TCI Practical Example: Reduction of Amide Group Using Zirconocene Chloride Hydride

We are proud to present the reduction of N,N-diethylnicotinamide to nicotinaldehyde using zirconocene chloride hydride.

Used Chemicals

• N,N-Diethylnicotinamide [D0514]
• Zirconocene Chloride Hydride [Z0010]
• THF

Procedure

Zirconocene chloride hydride (0.43 g, 1.68 mmol) was added to a reaction vessel and dried in vacuo for 3 hours. Then, a THF solution (4.1 mL) of N,N-diethylnicotinamide (200 mg, 1.12 mmol) was added under argon atmosphere and the reaction mixture was stirred at room temperature for 30 minutes. The mixture was purified by chromatography on silica gel (hexane : ethyl acetate = 2 : 1) to give nicotinaldehyde as a brown oil (80.0 mg, 0.07 mmol, 60% yield).

Experimenter's Comments

The reaction solution was monitored by TLC (hexane : ethyl acetate = 1 : 1) and UPLC.
The reaction vessel was dried up before use.

Analytical Data

Nicotinaldehyde

¹H NMR (400 MHz, DNSO-d₆); δ 10.09 (s, 1H), 9.07 (d, J = 1.4 Hz, 1H), 8.84 (dd, J = 5.0 Hz, 1.8 Hz, 1H), 8.23 (dt, J = 7.8 Hz, 2.1 Hz, 1H), 7.62 (dd, J = 8.5 Hz, 2.1 Hz, 1H).

Lead Reference

• Mild and Selective Hydrozirconation of Amides to Aldehydes Using Cp₂Zr(H)Cl: Scope and Mechanistic Insight
  • J. T. Spletstoser, J. M. White, A. R. Tunoori, G. I. Georg, J. Am. Chem. Soc. 2007, 129, 3408.