The amines are one of the most important classes of chemical compounds today. Amines that contain a ring-like structure - called an "aryl" group - are used widely in pharmaceuticals, such as the top-selling drugs Abilify, Crestor, Gleevec, and Lidoderm. EPFL scientists have now developed a method to produce aryl-containing amines in a cheap and easily scalable way. The work is published in Nature Communications.
Aromatic and heteroaromatic amines ((hetero)aryl amines) are central to medicinal chemistry. The process of making different amines is called amination, which 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 and Chi Wai Cheung at EPFL have now developed a new method for making (hetero)aryl amines through the reductive coupling of nitroarenes with organic compounds, without needing to go through the aniline step first. Using a simple 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.
The new method allows chemists to synthesize alkyl or aryl amines from directly from nitroarenes, which are often cheaper than anilines. Moreover, using nitroarenes directly is more step-economical than using anilines, since the latter have to be derived from nitroarenes anyway. In addition, certain anilines containing are difficult to produce, while their corresponding nitroarenes are readily available.
The authors state: "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."
This work was funded by the European Research Council (ERC).
Cheung CW, Hu X. Amine Synthesis via Iron Catalyzed Reductive Coupling of Nitroarenes with Alkyl Halides. Nature Communications 12 August 2016. DOI: 10.1038/NCOMMS12494