Methyl 4-(cyanoacetyl)benzoate

Chemical Properties

BEIGE FLAKY CRYSTALS

Uses

Methyl 4-(cyanoacetyl)benzoate may be used in chemical synthesis.

General Description

Methyl 4-(cyanoacetyl)benzoate (Methyl 4-(2-cyanoacetyl)benzoate) is an ester. Its various physical properties such as density, refractive index, melting point and boiling point have been reported.

Synthesis

General procedure for the synthesis of methyl 4-carbonitrile acetylbenzoate from methyl 4-chlorocarbonylbenzoate and cyanoacetic acid: cyanoacetic acid (1.7 g, 20 mmol, 2 eq.), MgSO4 (0.2 mg), and 2,2'-bipyridine (ca. 1 mg) were dissolved in tetrahydrofuran (100 mL), and the mixture was transferred to a three-necked flask containing a 500-mL three-necked flask that was equipped with two dropping funnels and a mechanical stirrer. The system was flushed with nitrogen and cooled to -78°C in a dry ice/acetone bath. A n-butyllithium solution (25 mL, 1.6 M hexane solution; 40 mmol, 4 eq.) was slowly added through the dropping funnel with stirring. When the solution took on a slight purple color, stirring was continued for 30 min, followed by the addition of a 5 mL methanol solution of methyl 4-chlorocarbonylbenzoate (10 mmol, 1 eq.) dropwise under stirring. During this process, the cloudy solution changed to yellow color. The reaction mixture was continued to be stirred at -78 °C for 1 h. Subsequently, the cooling bath was removed and the reaction was allowed to slowly warm up to room temperature and held for 1 h. The reaction was then allowed to warm up to room temperature and held for 1 h. The reaction was allowed to warm up to room temperature. A 1 M HCl solution (50 mL) was added dropwise, at which point the reaction solution became clear but remained yellow. Water (25 mL) and dichloromethane (50 mL) were added and the aqueous layer was extracted three times with the same volume of dichloromethane. The organic layers were combined, washed with saturated sodium bicarbonate solution (50 mL x 2), dried over magnesium sulfate, filtered, and concentrated on a rotary evaporator. Purification by fast chromatography (hexane:ethyl acetate=6:1) gave the target product in 50-80% yield.

References

[1] Tetrahedron Letters, 2011, vol. 52, # 19, p. 2440 - 2442