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Facile One-Pot Transformation of Arenes into Aromatic Nitriles under Metal-Cyanide-Free Conditions
Abstract
Electron-rich arenes bearing methyl or methoxy groups on the aromatic ring were treated with dichloromethyl methyl ether and ZnBr2, and then with molecular iodine and aq. ammonia to give the corresponding aromatic nitriles in good yields. Using this method, febuxostat was efficiently prepared from 4-bromophenol in four steps. The method can be used for the preparation of aromatic nitriles from arenes in one pot under metal-cyanide-free conditions.
The nitrile moiety is an important group that is found in pharmaceuticals and agrochemicals. In addition the nitrile can serve as a stable intermediate for amides, carboxylic acids, ketones, aldehydes, etc. As a result, many methods to make nitriles have been reported. In a new publication Togo et al. report their development of a one-pot metal-cyanide-free protocol to make electron-rich aromatic nitriles ( Eur. J. Org. Chem. 2015, 2023). The reaction first reacts arenes with zinc bromide (ZnBr2) and dichloromethyl methyl ether to make in situ the (dichloromethyl)arene, that then reacts with aq. ammonia and iodine to make the nitrile. The electron-rich aromatic nitriles are formed in moderate-to-high yields (59–94%). They demonstrate usefulness of this reaction by synthesizing febuxostat.
Facile One-Pot Transformation of Arenes into Aromatic Nitriles under Metal-Cyanide-Free Conditions
Article first published online: 9 FEB 2015
Tamura, T., Moriyama, K. and Togo, H. (2015), Facile One-Pot Transformation of Arenes into Aromatic Nitriles under Metal-Cyanide-Free Conditions. Eur. J. Org. Chem., 2015: 2023–2029. doi: 10.1002/ejoc.201403672
http://onlinelibrary.wiley.com/doi/10.1002/ejoc.201403672/abstract
