Management of the Heat of Reaction under Continuous Flow Conditions Using In-Line Monitoring Technologies

Abstract

This work presents a guideline for managing process safety under continuous flow conditions. In our previous work, we developed a Grignard reaction for use under such conditions. This reaction was completed in seconds and entailed a large amount of heat generation. To manage the heat of reaction, we quantitatively analyzed the reaction rate using ReactIR with a flow cell. The difference between quantitative values from HPLC and ReactIR was less than 1%, and the reaction rate was 94% in 0.4 s. Based on the reaction rate and the heat of reaction, we simulated the distribution of the internal temperature along the tube length and found the maximum difference from the measured internal temperatures to be 5 °C. This accuracy was suitable for evaluating and managing the heat of reaction. Our methodology can facilitate the discussion of process safety under continuous flow conditions.

The rise of continuous flow biocatalysis – fundamentals, very recent developments and future perspectives

“…215 Moreover, inline infrared (IR) and attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy is widely applied. 216,217 Fortunately, this spectroscopy technique allows to follow the change in concentration of the respected reactants and products during the reaction and also, beneficially, to observe the formation of some intermediates that could not be detected otherwise. A very recent and interesting real-time application uses a method that has long been established in chemical practice: nuclear magnetic resonance (NMR).…”

Continuous flow synthesis of pyridinium salts accelerated by multi-objective Bayesian optimization with active learning

“…and purications or separations coupled with automation enhances the utility of ow techniques for high-throughput and autonomous experimentation. [24][25][26][27][28][29][30][31] Recently, there have been tremendous strides made towards fully autonomous (closed-loop) experimentation systems that require little to no human intervention once initiated, and undoubtedly these systems will continue to mature and nd value in research labs. 16,[32][33][34] In contrast to fully self-driving labs, there are many opportunities for human-in-the-loop and interactive ML to make an impact.…”

Impact of Flow Configurations on Response Time and Data Quality in Real-Time, In-Line Fourier Transform Infrared (FTIR) Monitoring of Viscous Flows

“…The real-time, in-line monitoring of reactant and/or product concentrations in a reactive continuous flow is widely used both in research and developmental laboratories, as well as in the chemical industry. − It is typically achieved via a flow cell or a probe sensor that is connected or inserted into the flow stream. This in-line monitoring enables one to reliably analyze complex reaction systems and gain a better understanding of and better control over chemical processes with minimal flow intervention and without the need for disruptive and invasive sampling and off-line analysis. − From a safety perspective, it allows one to detect and monitor hazardous chemicals with minimal contact and accurately manage process safety under continuous flow conditions. , In addition, the in-line monitoring of the progress of a reaction is becoming even more important in the context of intensifying specialty and fine chemicals processing by transitioning from batch operations to continuous operations. − This batch-to-continuous transition requires a continuous in-line tracking of concentrations in order to perform rapid screening of reaction conditions, − identify key intermediate steps and reaction end points, , and develop robust and sensitive reaction kinetics and thermodynamic data − that can be used for process modeling, design, optimization, and scale-up of continuous flow processes.…”

“…4−6 From a safety perspective, it allows one to detect and monitor hazardous chemicals with minimal contact 7 and accurately manage process safety under continuous flow conditions. 8,9 In addition, the in-line monitoring of the progress of a reaction is becoming even more important in the context of intensifying specialty and fine chemicals processing by transitioning from batch operations to continuous operations. 10−12 This batch-to-continuous transition requires a continuous in-line tracking of concentrations in order to perform rapid screening of reaction conditions, 13−16 identify key intermediate steps and reaction end points, 17,18 and develop robust and sensitive reaction kinetics and thermodynamic data 19−22 that can be used for process modeling, design, optimization, and scale-up of continuous flow processes.…”