2-Iodophenylacetonitrile

Uses

2-Iodophenylacetonitrile may be used in the preparation of:

• 2-aminobiphen-2-ylacetonitrile
• ethyl (2-iodophenyl)iminoacetate hydrochloride
• 3,4-disubstituted 2-naphthalenamines

It may also be used in the preparation of the following nitriles:

• 2-(2-iodophenyl)-2-methylpropanenitrile
• 1-(2-iodophenyl)cyclopentanecarbonitrile
• 5-bromo-2-(2-iodophenyl)pentanenitrile
• 2-(2-iodophenyl)-2-propylpentanenitrile
• 1-(2-iodophenyl)cyclohexanecarbonitrile
• 1-(2-Iodophenyl)cyclopropanecarbonitrile

General Description

2-Iodophenylacetonitrile is a 2-aryl substituted nitrile. It reacts with lactams to form ring-fused isoquinolinones via palladium-catalyzed carboxamidation in tandem with aldol condensation.

Synthesis

Distilled dichloromethane (5 mL) was added to a 25 mL reaction tube under nitrogen protection. Subsequently, 161 mg (0.5 mmol) of iodobenzene diacetate was added. Next, 180 μL of trimethylsilyl trifluoromethanesulfonate (TMSOTf, 1.0 mmol) was added. The reaction mixture was stirred at room temperature for 5 min. After that, 198 mg (0.6 mmol) of 2-(tributylstannyl)acetonitrile was added at -78 °C and stirring was continued for 5 min, and the reaction process was monitored by thin layer chromatography (TLC). Upon completion of the reaction, 3 mL of saturated sodium bicarbonate solution was added to quench the reaction. The reaction was slowly warmed to room temperature and then extracted with dichloromethane (3 mL x 3). The organic phases were combined and dried over anhydrous sodium sulfate. It was subsequently concentrated under reduced pressure. Purification by column chromatography (Rf = 0.19, unfolding agent: petroleum ether/ethyl acetate = 40/1, v/v) afforded the target product 2-iodophenylacetonitrile as a white solid in 86% yield.

References

[1] Angewandte Chemie - International Edition, 2018, vol. 57, # 29, p. 9078 - 9082
[2] Angew. Chem., 2018, vol. 130, # 29, p. 9216 - 9220,5
[3] Patent: CN108409602, 2018, A. Location in patent: Paragraph 0022; 0023; 0024