Application Guide—Using the expression CMS Compact Benchtop Mass Spectrometer to Monitor and Optimize Flow Chemistry Reactions

Flow chemistry, in its original sense, refers to the completion of chemical reactions in a continuously flowing system. Unlike batch reactions, flow chemistry innovatively integrates traditionally separate and independent synthetic operations, thereby accelerating the synthesis process. In particular, it enables the realization of hazardous and otherwise difficult-to-achieve reaction conditions. As such, flow chemistry holds tremendous significance for the fields of green chemistry and laboratory automation.

Application Guide—Using the expression CMS Compact Benchtop Mass Spectrometer to Monitor and Optimize Flow Chemistry Reactions

2023-12-06

Flow chemistry, in its original sense, refers to the completion of chemical reactions in a continuously flowing system. Unlike batch reactions, flow chemistry innovatively integrates traditionally separate synthetic operations into a single, continuous process, thereby accelerating synthesis rates. In particular, it enables the realization of hazardous and otherwise difficult-to-achieve reaction conditions. As such, flow chemistry holds tremendous significance for the fields of green chemistry and laboratory automation.

Continuous-flow chemistry begins with two or more reactants—such as the initial reactants—which are pumped into the reaction chamber, reaction tube, or microreactor at a set flow rate. In these microreactors, the different reactants are mixed and allowed to undergo chemical reactions. Depending on the reaction kinetics and the flow rates of the reactants, it is essential to ensure that the reactants achieve a specific residence time within the microreactor, thereby attaining the desired reaction conversion rate. Since the reaction takes place in a continuously flowing fluid, it is naturally desirable to monitor the reaction in real time to gain insight into various reaction conditions; thus, reaction monitoring becomes particularly important.

In this application guide, we present two different reaction examples of flow chemistry synthesis using expression CMS.

Experimental method

Mass Spectrometry System: expression® CMS Compact Benchtop Mass Spectrometer

I. Instrument Setup

Two slightly different setups were used in the experiment. In the first method, the reaction mixture was injected into the mass spectrometer using a syringe (via a valve; Figure 1).

In the second scenario, a syringe pump system is used to deliver reagents, and valves are switched automatically to transfer samples into the mass spectrometer (Figure 2). The CMS data are then fed into reaction optimization and data processing software.

II. Mass Spectrometry Conditions

Scan range: m/z 100–m/z 800;

Scan time: 400 ms;

Scanning speed: 1750 m/z units/s;

Flow rate: 0.2 mL/min;

Mobile phase: MeCN, H2O (50:50) (0.1% formic acid);

Ion source: ESI;

Mode: Positive Ion Mode

Capillary Temp: 200℃;

Capillary Voltage: 80V;

Source Offset: 30;

Source Gas Temp: 250℃;

ESI Voltage: 3500V;

Experimental results

The reaction data (Figure 3) show real-time monitoring of the increase in product and the decrease in reactants, while also revealing intermediates and impurities. This provides valuable information about the reaction, offering experimentalists an advantage that cannot be achieved through other techniques in terms of controlling the reaction or process.

Using a CMS to monitor reactions in flow cells with varying residence times allows for close monitoring of the reaction progress, enabling the identification of conditions under which large amounts of impurities or intermediates are formed and facilitating the selection of the optimal residence time. This reaction proceeds via two distinct intermediates; if the reaction is not properly controlled and optimized, it could ultimately give rise to impurities. Therefore, close monitoring and thorough understanding of this process are crucial.

In this experiment, the reagent ratios are automatically determined and the reaction mixtures containing different components are delivered via a flow chemistry device. The expression CMS monitors raw materials, products, and intermediates in real time, which facilitates subsequent optimization of the reaction.

Conclusion

1. The expression CMS is an ideal mass spectrometer for use in conjunction with flow chemistry systems.

2. The CMS features multiple signal input and output ports, giving it unique and flexible interface capabilities.

3. Expression CMS analysis provides detailed, real-time information about reactions that is typically unavailable from other analytical techniques (such as chromatography, nuclear magnetic resonance, infrared/near-infrared, and ultraviolet).

4. A variety of ion source options, including ESI and APCI, expand the range of reactions that can be monitored.

5. Advion Interchim Scientific has extensive experience in solutions that combine mass spectrometry with innovative synthetic chemistry, and can offer a variety of mass-spectrometry-based coupling approaches.

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