Used in synthesis and pharmaceutical development, flow reactors offer both time and resource savings, when compared with off-line methods. Enabling rapid screening of key process parameters to ensure optimal conditions are reached, such as reaction temperature, residence time and molarity ratio. Mass spectrometry provides compound specificity for improved on-line characterisation and monitoring but can introduce intrinsic challenges. In this blog post we examine the potential for mass detection in reaction monitoring and the challenges facing end-users.
What is measured in flow reactors?
Even in simple synthesis step processes, the end-user must monitor reagents, intermediates and products. The relative concentration of these species will describe how the reaction is progressing. The key parameters governing the flow reaction, such as residence time in the reactor, temperature and molarity ratio, can then be adjusted accordingly with the reactor apparatus. Generally, it is desirable to achieve a ‘steady-state’: that is, a level of variable where further adjustment does not lead to further improvements in reaction response.
How to measure what’s going on in the flow reactor?
Ideally, on-line measurement is a favoured technique, providing in real-time information necessary for understanding the reaction . Many laboratories are simply not equipped with the adequate on-line instrumentation, and many settle for sending samples to specialised labs either within the same institution or even remotely, thus limiting the data that can be taken, which introduces more steps in the reaction, the increased possibility of error, and increases time and resource.
Mass spectrometry (MS) is ideal for on-line measurements, offering unrivalled selectivity over traditional alternative methods such as on-line Infrared (IR), Ultraviolet (UV) and Nuclear Magnetic Resonance (NMR).
Uptake of MS technology as a routine analysis method is limited, as it is traditionally seen as expensive, difficult to use and maintain, and requires significant specialist laboratory resource and infrastructure.
Compact “Point-of-Need” MS as tool for on-line flow reaction
For all its power as an analytical tool, traditional mass spectrometry is typically not space efficient. There is requirement for an external roughing vacuum pump, a dedicated computer, and a nitrogen generator severely restricts placement of traditional, full size instruments in the majority of synthetic lab environments. When considering this, one can imagine that a cramped fume hood is not ideally suited for a traditional MS. The Microsaic MiD® series of miniature mass spectrometers can achieve this due the unique small footprint that encompasses all necessary vacuum pumps inside one box with no external pumps needed. This greatly improves the ability to deploy this technology in confined work areas such as alongside flow reactors, inside fume hoods.
Organic chemists will be familiar with the somewhat extreme conditions that are present in reaction vessels. End-users often complain that high concentrations of compounds eluting from the reaction vessel will clog up their sensitive mass spec. The eluent could also be highly acidic or basic, or contain solvents that are not suitable for MS. Significant sample modification is therefore required before the MS analysis.
Microsaic’s fluidics platform the MiDas™ incorporates an attenuator and a make-up pump connected to a solvent reservoir. These parts work together to provide controllable dilution factors that can be adjusted to the required level using integrated software. Together the MiD® and MiDas™ provide a platform that can be tailored to most flow reaction applications.
To see examples of how Microsaic products have integrated with flow reactor apparatus and give powerful real-time data, to aid the development of chemical synthesis please see our Application Notes section of our website