Highly reactive chemistries are widely used in the synthesis 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:
Examples of highly reactive chemistries include:
- Azide chemistry
- Diazo chemistry
- Grignard chemistry
- Lithium chemistry
- Phosgene chemistry
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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 dangerous reaction materials, and maximization of productivity are critical to the successful development of highly reactive chemistries.
METTLER TOLEDO has developed advance process analytical tools for the effective development and operation of highly reactive chemistries by providing:
- Precise control of critical reaction conditions such as temperature, pressure, mixing rate, reagent dosing rates, etc.
- In situ real-time monitoring of:
- Reaction progression and mechanisms, including identification of reaction on-set, reaction rate, kinetics and desired reaction endpoint
- Generation and accumulation of highly dangerous reactants, intermediates, or by-products
Figure 1. The delay in formation of Grignard after addition of 5% Ar-Br substrate is detected and displayed in real-time by ReactIRTM
Figure 2. The accumulation of hydroxylamine intermediate during the hydrogenation of nitrobenzene is detected and displayed in real-time by ReactIRTM
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 using ReactIRTM (Figure 1 and 2) 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 the real-time calorimetry (RTCalTM) capability of METTLER TOLEDO RC1 automated reactors (Figure 3) and controlled to avoid runaway conditions using the RC1 thermostat
- 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 ReactIRTM analysis under precisely controlled reaction conditions.
Figure 3. The fast heat flow at the initial state (1st kinetic regime) of the pryzine carboxamide hydrogenation is recorded and displayed in real-time by the calorimetry feature of RC1TM
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 directly by ReactIRTM ATR-FTIR spectrometry (Figure 4) and by RC1 and RTCalTM 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
Figure 4. ReactIRTM detects and displays in real-time the formation of anhydride due to H2O intrusion, the intertness of the anhydride under the hydrogenation condition, the rates and progressions of anhydride formation and RCOCI reduction to RCHO. This is a case when the HPLC assay is clearly inferior.
Faster Process Optimization
- Obtaining a high yield of desired product is dependant 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 such as ReactIRTM and reaction calorimetry in precisely controlled automated reactors.
- 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 (Figure 4) - 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 ReactIRTM spectrometry 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 very time consuming and labor intensive. The use of in situ analytics, such as ReactIRTM spectrometry and RC1 calorimetry can eliminate offline sampling difficulties, produce real-time results (Figure 4), and increase operational productivity by both reducing batch cycle time and avoiding labor intensive operations.
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