Obtaining Kinetics From Continuous Processes: Sampling Multiple Time Points Concurrently With a Single Valve Rotation

Abstract

The manufacturers of fine chemicals and pharmaceuticals are beginning to accept flow chemistry as a production alternative following the lead of commodity chemical manufacturers, who have been producing goods in continuous format for decades. The ability to trace time backwards by retracting the spatial length of a flow reactor is perhaps one of the biggest advantages of flowed synthesis. However, in the absence of an appropriate tool that would allow scientists to sample throughout the entire space of a production line, the theory is not possible to put into practice. A step in this direction has been taken with the invention of a unique, multi‐port valve/flow reactor that allows the chemist to simultaneously sample multiple timepoints of a chemical transformation with one single valve actuation, thereby capturing instantaneously the entire reaction course of the flowed chemical process.

Rapid Kinetic Screening via Transient Timesweep Experiments in Continuous Flow Reactors

“…Secondly, since reaction time is correlated via flow rate and volume, it is possible to directly monitor reaction progress along the axis of a flow reactor. An excellent example of this concept was recently published by Organ et al [18] They created a multi-port valve/flow reactor that was able to sample at multiple points in time with one single valve actuation. Even though interesting, this approach is, however, still limited in the number of datapoints that can be collected.…”

Sampling and Analysis in Flow: The Keys to Smarter, More Controllable, and Sustainable Fine‐Chemical Manufacturing

“…Av ery recent report describes aP AT sampling solution that enables the simultaneous sampling of IPC samples at various reactor lengths in asingular flow reactor. [7] A24-port valve was used to intercept four IPC samples simultaneously using four sampling loops (Figure 14, L1-L4). This device was used to monitor the aza-Michael reaction between aniline (9, Figure 15) and 3-buten-2-one (10).…”

“…Flow chemistry,the science that forms the foundation of chemical CM, allows chemists to transform reaction time (known as reactor residence time in CM) into reactor length, atangible physical dimension that enables scientists to unwind "time" through "space", and to minimize the impact from transient process failures.T his increases the chance of keeping ap roduction run immune from temporary glitches and, ultimately,f rom batches being scrapped, thus ushering an era of more reliable pharmaceutical manufacturing that was almost unthinkable just ad ecade ago. [7][8][9] Thek ey to this reliability lies in the detection of transient failures on time (real-time analysis) or in advance (data trending analysis). [10][11][12][13] PATa llows scientists to design, analyze,a nd control manufacturing processes through the measurement of critical process parameters (CPPs) and the analysis of critical quality attributes (CQAs), which, in turn, helps them monitor the chemical state of aproduction run in real time.…”