ChemicalBook CAS DataBase List 4-CHLOROBENZOYLACETONITRILE

4-CHLOROBENZOYLACETONITRILE synthesis

9synthesis methods

Product Name:4-CHLOROBENZOYLACETONITRILE
CAS Number:4640-66-8
Molecular formula:C9H6ClNO
Molecular Weight:179.6

122-01-0
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$13.00/25g

372-09-8
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$20.00/25g

4640-66-8
253 suppliers
$6.00/1g

Yield:4640-66-8 80%

Reaction Conditions:

Stage #1:cyanoacetic acid with [2,2]bipyridinyl;n-butyllithium;magnesium sulfate in tetrahydrofuran;hexane at -78; for 0.5 h;Inert atmosphere;
Stage #2:4-chloro-benzoyl chloride in tetrahydrofuran;methanol;hexane at -78 - 20;Inert atmosphere;
Stage #3: with hydrogenchloride in tetrahydrofuran;methanol;hexane;water

Steps:

Synthesis of β-keto nitriles
General procedure: Cyanoacetic acid (1.7 g, 20 mmol, 2 equiv), 0.2 mg MgSO₄, and ~1 mg 2,2'-bipyridyl was dissolved in tetrahydrofuran (100 mL) and placed in a 500 mL three-neck flask fitted with two dropping funnels and a mechanical stirrer. The system was flushed with nitrogen and cooled to -78 C with a dry ice/ acetone bath. An n-butyl lithium solution (25 mL, 1.6 M in hexanes; 40 mmol, 4 equiv) was added via a dropping funnel with stirring. Once the solution turned slightly purple it was stirred (30 min) after which the acid chloride (10 mmol, 1 equiv) in 5 mL of methanol was added drop-wise with stirring. During this process, the cloudy solution took on a yellow color. The solution was stirred at -78 C for one hour, then the bath was removed and the reaction was allowed to return to room temperature for one hour. An HCl solution (50 mL, 1M) was added drop-wise. At this point, the reaction became clear, while remaining yellow. Water (25 mL) and CH₃Cl (50 mL) were added. The aqueous layer was extracted three times with the same volume of CH₃Cl. The combined organic layers were washed with two portions (50 mL) of saturated sodium bicarbonate solution and dried over magnesium sulfate, filtered, and reduced on a rotoevaporator. Samples were purified by flash chromatography 6 Hex : 1 EtOAc resulting in percent yields from 50-80%.

References:

Nowill, Randall W.;Patel, Trisha J.;Beasley, David L.;Alvarez, Jose A.;Jackson III, Elizah;Hizer, Todd J.;Ghiviriga, Ion;Mateer, Scott C.;Feske, Brent D. [Tetrahedron Letters,2011,vol. 52,# 19,p. 2440 - 2442] Location in patent:supporting information; experimental part

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