Carbonic acid anhydrides are important synthetic intermediates and, therefore, are produced industrially on a multi-ton scale. Acetic anhydride, for example, is needed to produce the widely used painkillers aspirin and paracetamol. The established synthesis routes for acetic anhydride generally rely on rare and expensive rhodium catalysts or toxic and reactive reagents like ketene. Replacing rhodium with a more abundant metal could improve the production of acid anhydrides.
Neal P. Mankad, University of Illinois, Chicago, USA, and colleagues have developed a copper-catalyzed reaction for the synthesis of aliphatic, symmetric acid anhydrides from alkyl iodides and carbon monoxide. The reaction is mediated by blue LED light (390 nm). The transformation was optimized using the conversion of 3-phenyl-1-iodopropane in acetonitrile as an example. Under 6 atm of CO, using potassium carbonate as an added base and CuBr∙SMe2 as a copper precatalyst, the team obtained a yield of 97 % after 8 h reaction time. The isolation of the pure product was achieved by simple filtration and subsequent removal of volatile components.
The reaction is compatible with a wide range of alkyl iodides, but bulkier substituents lead to slightly decreased yields. Alkyl bromides do not react directly, but were successfully converted after the addition of NaI for the in-situ formation of the corresponding iodide analogues. After the addition of NaI, tosylates were also successfully converted to the desired anhydrides.
During the reaction, the researchers observed the precipitation of a solid material, which was found to be essential for the catalysis. According to X-ray photoelectron spectroscopy (XPS) measurements, it contains Cu(0) species. This could indicate the presence of copper nanoparticles as the catalytically active species. After adaption to larger scales, this procedure could be an alternative for the industrial synthesis of carbonic acid anhydrides that does not depend on rhodium catalysis.
- Light-Mediated Synthesis of Aliphatic Anhydrides by Cu-Catalyzed Carbonylation of Alkyl Halides,
Pinku Tung, Neal P. Mankad,
J. Am. Chem. Soc. 2023.