Authors:Daniel Blanco-Ania and Floris P. J. T. Rutjes
While continuous-flow chemistry is steadily increasing its footprint in academic research and in the manufacturing of pharmaceutical intermediates and fine chemicals, the attention for flow chemistry in educational programs is on average rather limited. This account is meant to provide a personal overview of the possibilities to address the involvement of flow chemistry in the various stages of chemical education.
Authors:René Becker, Sebastiaan (Bas) A.M.W. van den Broek, Pieter J. Nieuwland, Kaspar Koch and Floris P.J.T. Rutjes
To expand the knowledge base for fundamental organic reactions in continuous flow, the α-bromination of acetophenone was successfully transformed from a known batch procedure to a continuous flow process in 99 % yield through D-optimal optimisation and subsequent scale-up of the validated optimum. Using a preparative scale system, a space–time yield of 0.26 kg/m3/s (comparable literature batch reaction 0.24 kg/m3/s) was achieved under conditions suitable for laboratory and small-scale industrial application where high yield or purity is required, e.g., when expensive substrates are used.
Authors:Caroline Bosch, Pablo López-Lledó, Josep Bonjoch, Ben Bradshaw, Pieter J. Nieuwland, Daniel Blanco-Ania and Floris P. J. T. Rutjes
An Amberlite IR 120 H-promoted one-pot Fischer indolization from a cis-decahydroquinoline using a range of phenylhydrazines led to compounds with the pyrido[2,3-a]carbazole scaffold. The process may be conducted either in batch mode or in a continuous manner in a flow reactor. The stereochemical course of the Fischer indole reaction changed in going from using free phenylhydrazine to the corresponding hydrochloride in batch conditions, whereas, with the short reaction times in continuous flow, no changes due to isomerization processes were observed.
Authors:Mariëlle M.E. Delville, Jasper J.F. van Gool, Ivo M. van Wijk, Jan C.M. van Hest and Floris P.J.T. Rutjes
Cyanohydrins are synthetically versatile chiral building blocks in organic synthesis. They can be conveniently synthesized in enantiomerically pure form via chemoenzymatic hydrogen cyanide addition onto the corresponding aldehyde using hydroxynitrile lyase. Recently, we reported that such transformations can be efficiently carried out in a continuous flow manner using microreactors. Since racemization of enantiopure cyanohydrins occurs readily under slightly basic conditions, they should be protected before the follow-up reactions, preferably under acidic conditions. In this contribution, we demonstrate that the methoxyisopropyl protection of mandelonitrile can be conveniently optimized in an automated microscale continuous flow system and subsequently scaled up under the same conditions by applying a larger flow reactor.