Trimethylsilyl Cyanide

• p-Tolualdehyde [T1073]
• Methylamine (40% in Methanol, ca. 9.8mol/L) [M1016]
• Trimethylsilyl Cyanide (=TMSCN) [T0990]
• Methanol

Methylamine (40% in methanol, ca. 9.8 mol/L, 1.0 mL, 10 mmol, 2.0 eq.) was added to a solution of p-tolualdehyde (601 mg, 5.0 mmol) in methanol (12 mL) at room temperature and the mixture was stirred for 1 hour. Then TMSCN (744 mg, 7.5 mmol, 1.5 eq.) was added to the mixture and stirred at room temperature for overnight. The solvent was removed under reduced pressure. The residue was diluted with ethyl acetate (15 mL) and water (15 mL) and separated. The water layer was extracted with ethyl acetate (15 mL x 2) and the organic layer was washed with 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 1 as a pale yellow liquid (605 mg, 76% yield).

The reaction mixture was monitored by UPLC.
This experiment was performed in a fume hood due to the possibility of generating hydrogen cyanide.

Compound 1

¹H NMR (400 MHz, CDCl₃); δ 7.40 (d, J = 8.0 Hz, 2H), 7.21 (d, J = 8.0 Hz, 2H), 4.72 (2, 1H), 2.57 (s, 3H), 2.37 (s, 3H), 1.47 (brs, 1H).

• Racemase Activity of B. cepacia Lipase Leads to Dual-Function Asymmetric Dynamic Kinetic Resolution of α-Aminonitriles
• P. Vongvilai, M. Linder, M. Sakulsombat, M. S. Humble, P. Berglund, T. Brinck, O. Ramström. Angew. Chem. Int. Ed. 2011, 50, 6592.