A microfluidic high-resolution NMR flow probe based on a novel stripline detector chip is demonstrated. This tool is invaluable for the in situ monitoring of reactions performed in microreactors. As an example, the acetylation of benzyl alcohol with acetyl chloride was monitored. Because of the uncompromised (sub-Hz) resolution, this probe holds great promise for metabolomics studies, as shown by an analysis of 600 nL of human cerebrospinal fluid.

The generally accepted benefits of small lateral dimensions of microreactors (1 microm to 1 mm) enable a different way of performing synthetic chemistry: Extremely short contact times in the millisecond range can circumvent the need for performing highly exothermic and fast reactions at very low temperatures. In order to fully exploit this technology, such fast processes need to be redesigned and investigated for optimal reaction conditions, which can differ drastically from the ones traditionally applied. In a comprehensive study, we optimized the selective Swern-Moffatt oxidation of benzyl alcohol to benzaldehyde by varying five experimental parameters, including reaction time and temperature. Employing an ultrashort mixing and reaction time of only 32 ms, the optimal temperature was determined to be 70 degrees C, approximately 150 degrees C higher than in the conventional batch conditions. This remarkable difference shows both the potency of continuous-flow chemistry as well as the urgency of a paradigm shift in reaction design for continuous-flow conditions.

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.

A flow chemistry method for the synthesis of pyrroles was developed. The method was optimized in 0.13 to 7 μL microreactors in continuous flow, reaching yields of nearly 100%. Subsequently, the method was scaled up in continuous flow using a 9.6-mL internal volume, glass, microstructured flow reactor, leading to production of a pyrrole derivative at a rate of 55.8 g per hour .

Three factors (temperature, stoichiometry and reaction temperature) were investigated in continuous flow microreactors in an automated fashion for optimization of the removal of the pmethoxyphenyl (PMP) protecting group, thereby consuming only minute amounts of substrate (0.2 mg/sample). The optimal reaction conditions were also applied to a larger microreactor system, in which the corresponding free amine was obtained at a preparative scale.