Researchers at the Ecole Polytechnique Federale De Lausanne (EPFL) say they have developed a method to produce aryl-containing amines in a cheap and easily scalable way. Their study (“Amine Synthesis via Iron Catalysed Reductive Coupling of Nitroarenes with Alkyl Halides”) is published in Nature Communications.
The amines are one of the most important classes of chemical compounds today. Amines that contain a ring-like aryl group are used widely in pharmaceuticals, such as the top-selling drugs Abilify® (aripiprazole), Crestor® (rosuvastatin), Gleevec® (imatinib mesylate), and Lidoderm® (lidocaine patch 5%). The process of making different amines (amination) involves connecting an amine to an organic molecule. The amine itself must first be prepared in advance by the hydrogenation of anilines, which are used as a nitrogen source and are derived from nitroarenes.
Xile Hu, Ph.D., and Chi Wai Cheung, Ph.D., at EPFL developed a technique for making (hetero)aryl amines through the reductive coupling of nitroarenes with organic compounds, without needing to go through the aniline step first. Using an iron catalyst, the researchers were able to couple amines to a number of alkyl halides, a group of organic compounds widely used in commercial products.
The method was shown to have a high tolerance to functional groups, including some that require protection under conventional amine synthesis, making them versatile and well suited for a broad range of applications, according to the investigators.
The new method allows chemists to synthesize alkyl or aryl amines directly from nitroarenes, which are often cheaper than anilines. Moreover, using nitroarenes directly is more step-economical than using anilines, because the latter have to be derived from nitroarenes anyway, add the scientists. In addition, certain anilines containing are difficult to produce, while their corresponding nitroarenes are readily available.
“From these points of view, the current method can be considered as a valuable alternative to the conventional amination methods such as direct alkylation and reductive amination,” said Dr.Hu.