How To Optimize A Highly Reactive Chemistry

Highly Reactive Chemistry

Highly Reactive Chemistry

Highly reactive chemistries are used in the syntheses of drug molecules, special polymer products, herbicides and other agriculture products, high energy materials, and even special materials like nano-particles and chemo-sensors.

Examples of highly reactive chemistries include:

  • Azide chemistry
  • Diazo chemistry
  • Grignard chemistry
  • Lithium chemistry
  • Phosgene chemistry


To take full advantage of highly reactive chemistry, chemists and chemical engineers must know how to handle the inherent hazardous nature due to high instability, fast energy release, acute toxicity or bioactivity of the reaction mixtures.  Prevention of runaway reactions or explosions, minimization of human exposure to the dangerous reaction materials, and maximization of productivity are critical to the successful development of highly reactive chemistries.

Advanced Process Analytical Technology (PAT) tools are used for the effective development and operation of highly reactive chemistries by providing:

  • Precise control of critical reaction conditions including temperature, pressure, mixing rate, reagent dosing rates
  • In situ real-time monitoring of
    • Reaction progression and mechanisms, including identification of reaction onset, reaction rate, kinetics and desired reaction endpoint
    • Generation and accumulation of highly dangerous reactants, intermediates or by-products

Ensure Safe Operation

  • Runaway reactions can be triggered by a delay of reaction on-set leading to an accumulation of highly reactive reagent or intermediate.  In situ monitoring of reactant concentration provides real-time information and insight for control to avoid dangerous buildup conditions.
  • Fast heat release, another runaway trigger, can be monitored in real-time using real-time calorimetry and controlled to avoid runaway conditions
  • Control parameters that are critical for safe process scale-up and operation can be effectively identified and evaluated through data-rich experiments using real-time analysis under precisely controlled conditions

Minimize Human Exposure

  • Manual sampling and analysis by offline analytics expose human operators to the risk of contacting highly toxic, acute or bioactive materials.  Such exposure is avoided or minimized through the use of in-process measurements
  • Reaction progression and end-of-reaction can be measured by ATR-FTIR spectroscopy and by calorimetric data – without the need for offline sampling and measurement
  • Using real-time analytics and automated reactors also helps prevent explosions or runaway reactions which could expose large numbers of people to hazardous materials

Faster Process Optimization

  • Obtaining a high yield of desired product is dependent on detailed process knowledge and the ability to reliably control and replicate the optimized operating conditions.  More efficient techniques can be realized through the combined use of in situ real-time analytics and reaction calorimetry
  • In situ real-time analytics can provide direct reaction kinetics data and insight into the mechanisms that cannot be identified or confirmed by conventional offline techniques – saving time and effort in process development
  • Defining optimal process conditions can become a bottleneck due to the limited number of experiments and limited information obtained through traditional laboratory techniques.  Parallel automated reactors with real-time in situ FTIR can increase the number of experiments performed each day and can dramatically increase the process knowledge produced in each set of data-rich experiments
  • Grabbing samples for offline analysis – especially in large scale production – can be time consuming and labor intensive.  The use of real-time in situ FTIR and reaction calorimetry can eliminate offline sampling difficulties, produce real-time results, and increase operational productivity by both reducing batch cycle time and avoiding labor intensive operations

During the Reducing the Risks of Highly Reactive Chemistry (Part 2) On-Demand Webinar, Paul Scholl discusses how to:

  • optimize the synthesis step
  • increase lab safety
  • avoid unnecessary exposure and incident

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