American Chemical Society
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Continuous Flow Production of Thermally Unstable Intermediates in a Microreactor with Inline IR-Analysis: Controlled Vilsmeier–Haack Formylation of Electron-Rich Arenes

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journal contribution
posted on 2012-05-18, 00:00 authored by Sebastiaan (Bas) A. M. W. van den Broek, Jeroen R. Leliveld, René Becker, Mariëlle M. E. Delville, Pieter J. Nieuwland, Kaspar Koch, Floris P. J. T. Rutjes
The Vilsmeier–Haack formylation of aromatic compounds is a well-established process in organic synthesis, largely driven by the fact that the resulting aldehydes are generally useful intermediates for the synthesis of fine chemicals and pharmaceutical products. Industrial-scale production, however, is often hampered by laborious procedures requiring the use of hazardous chemicals to produce the highly reactive intermediates. In order to circumvent these issues, a flow chemistry approach was developed. This article describes the design and semiautomated optimization of the Vilsmeier–Haack formylation in continuous flow and subsequent scale-up to preparative volumes in an intrinsically safe manner.