
Continuous Measurement of Isocyanate
Optimize Process Robustness & Quality
Isocyanates are critical building blocks for high performance polyurethane-based polymers that make up coatings, foams, adhesives, elastomers, and insulation. Concerns over exposure to residual isocyanates led to new limits for residual isocyanates in new products. Traditional analytical methods for measuring the residual isocyanate (NCO) concentration using offline sampling and analysis raise concerns with:
- Long wait times for offline analytical results, making it impossible to make real-time decisions, leading to inconsistent product quality and reduction in production capacity
- Sufficient process knowledge lacking at any given time point
- Exposure to NCO samples increasing the risk of sensitization and human health risks

Continuous In Situ Reaction Analysis
Providing Selectivity and Sensitivity
In situ monitoring with process analytical technology addresses these challenges. Specifically, in situ mid-IR spectroscopy with an attenuated total reflectance (ATR) sensor is an ideal choice due to its selectivity and sensitivity. Inline FTIR spectroscopy offers a straight-forward way to monitor reaction initiation, progression, conversion, intermediate (transient and/or highly reactive) formation, and endpoint in real time. FTIR spectroscopy can quantify NCO, polyol, by-products, and pre-polymer concentrations under reaction conditions, without taking samples for offline analysis. This enables manufacturers and formulators to ensure that product quality specifications, personnel safety, and environmental regulations are met.

Monitoring Prepolymer Reactions
Inline FTIR Spectroscopy Case Study
In this example, a diisocyanate reacts with a polyol. Several critical process parameters may affect the residual diisocyanate in the product, including temperature of the reaction, quality of the incoming starting material, feed rates, reaction kinetics, and reaction time.

To track reaction progression, an in situ FTIR spectroscopy probe is inserted directly into the vessel for the duration of the batch. Mid-infrared spectra are recorded every 60 seconds and plotted over time creating a three dimensional waterfall graph as shown to the right. This plot depicts how a decrease in reactants is concurrent with an increase in the product as time progresses. Results can also be depicted via reaction progression, displaying a plot of the relative concentration of each reaction component as a function of reaction time.

The mid-infrared absorbance values of the diisocyanate component trend are correlated to the ASTM titration method. If a trend deviates from expected values, the in situ measurement can immediately detect the change from optimum or expected, and provide engineers and plant operators with the opportunity to make the necessary corrections during development or manufacture of the prepolymer. This actionable information available in real-time reduces or eliminates the need to re-work batches that do not meet quality standards; this ensures residual NCO concentration meets specifications, while optimizing production capacity and lowering operating costs.

Control Residual Isocyanates
In situ monitoring with PAT provides process understanding to quantify isocyanate (NCO), polyol, by-products, and pre-polymer concentrations in real-time. In this paper, in situ mid-infrared spectroscopy was applied to ensure product quality, personnel safety, and environmental regulations were met.

PAT in Literature
Publications in Scientific Journals
Infrared spectroscopy is widely used to improve the control of residual isocyanates (NCO). Researchers in academia and industry employ in situ mid-FTIR spectroscopy routinely to provide comprehensive information rich experimental data that is used to advance research.

In Situ FTIR Spectroscopy
Reaction Kinetics, Pathway, and Mechanism
In situ ReactIR FTIR spectroscopy provides continuous monitoring of key reaction species and reaction progression. ReactIR provides specific information about reaction initiation, conversion, intermediates, and endpoint - even under challenging conditions that make offline sample and analysis difficult. Combining automated synthesis reactors with in situ analytical tools provides an additional level productivity by controlling and recording all reaction parameters 24 hours a day.
Applications
Applications Related to Controlling Residual Isocyanate
Isocyanates are critical building blocks for high performance polyurethane-based polymers that make up coatings, foams, adhesives, elastomers, and insulation. Concerns over exposure to residual isocyanates led to new limits for residual isocyanates in new products. Traditional analytical methods for measuring the residual isocyanate (NCO) concentration using offline sampling and analysis raise concerns. In situ monitoring with process analytical technology addresses these challenges and enables manufacturers and formulators to ensure that product quality specifications, personnel safety, and environmental regulations are met.
Measuring and understanding polymerization reactions, mechanisms, kinetics, reactivity ratios, and activation energies lead researchers to employ in situ infrared spectroscopy as a routine technique to gain comprehensive, information-rich data that is used to advance research in a shorter time frame.
Knowledge of impurity kinetics and mechanism of formation is important in determining reaction end-point in chemical and process development studies. Accurate, reproducible, and representative reactions samples are necessary for these studies.
In situ chemical reaction kinetics studies provide an improved understanding of reaction mechanism and pathway by providing concentration dependences of reacting components in real-time. Continuous data over the course of a reaction allows for the calculation of rate laws with fewer experiments due to the comprehensive nature of the data. Reaction Progression Kinetics Analysis (RPKA) uses in situ data under synthetically relevant concentrations and captures information throughout the whole experiment ensuring that the complete reaction behavior can be accurately described.
Continuous flow chemistry opens options with exothermic synthetic steps that are not possible in batch reactors, and new developments in flow reactor design provide alternatives for reactions that are mixing limited in batch reactors. This can often result in better product quality and higher yield. When coupled with Process Analytical Technology (PAT), flow chemistry allows for rapid analysis, optimization, and scale-up of a chemical reaction.
Grignard reactions are one of the most important reaction classes in organic chemistry. Grignard reactions are useful for forming carbon-carbon bonds. Grignard reactions form alcohols from ketones and aldehydes, as well as react with other chemicals to form a myriad of useful compounds. Grignard reactions are performed using a Grignard reagent, which is typically a alkyl-, aryl- or vinyl- organomagnesium halide compound. To ensure optimization and safety of Grignard reactions in research, development and production, in situ monitoring and understanding reaction heat flow is important.
Hydrogenation reactions are widely used in the manufacture of both bulk and fine chemicals for reducing multiple bonds to single bonds. Catalysts are typically used to promote these reactions and reaction temperature, pressure, substrate loading, catalyst loading, and agitation rate all effect hydrogen gas uptake and overall reaction performance. Thorough understanding of this energetic reaction is important and PAT technology such as in situ FTIR, calorimetry and automated, in situ sampling in support of HPLC analysis ensure safe, optimized and well-characterized chemistry.
Highly reactive chemistry is a terminology used to describe chemical reactions that are particularly challenging to handle and develop due to the potentially hazardous and/or energetic nature of the reactants, intermediates and products that are present during synthesis. These chemistries often involve highly exothermic reactions which require specialized equipment or extreme operating conditions (such as low temperature) to ensure adequate control. Ensuring safe operating conditions, minimizing human exposure, and gaining the maximum amount of information from each experiment are key factors in successfully designing and scaling-up highly reactive chemistries.
Many processes require reactions to be run under high pressure. Working under pressure is challenging and collecting samples for offline analysis is difficult and time consuming. A change in pressure could affect reaction rate, conversion and mechanism as well as other process parameters plus sensitivity to oxygen, water, and associated safety issues are common problems.
Hydroformylation, or oxo synthesis/process, is important for the production of olefins to aldehydes and aldehydes from alkenes. Hydroformylation reactions are performed at high pressure and can be challenging to sample due to the extreme reaction conditions, as well as the toxic, flammable, and reactive raw materials and reagents.
Catalysts create an alternative path to increase the speed and outcome of a reaction, so a thorough understanding of the reaction kinetics is important. Not only does that provide information about the rate of the reaction, but also provides insight into the mechanism of the reaction. There are two types of catalytic reactions: heterogeneous and homogeneous. Heterogeneous is when the catalyst and reactant exist in two different phases. Homogeneous is when the catalyst and the reactant are in the same phase..
One of the four major classes of chemical reactions, synthesis reactions are represented by important examples in organic synthesis, catalyzed chemistry, polymerizations and inorganic/organometallic chemistry. In the simplest case, a synthesis reaction occurs when two molecules combine to form a third, more complex product molecule. Often, synthesis reactions are more complex and require a thorough understanding of the kinetics and mechanisms of the underlying chemistry, as well as carefully controlled reaction conditions.
Design of Experiments (DoE) requires experiments to be conducted under well-controlled and reproducible conditions in chemical process optimization. Chemical synthesis reactors are designed to perform DoE investigations ensuring high quality data.
Reaction mechanisms describe the successive steps at the molecular level that take place in a chemical reaction. Reaction mechanisms cannot be proven, but rather postulated based on empirical experimentation and deduction. In situ FTIR spectroscopy provides information to support reaction mechanisms hypotheses.
Organometallic Synthesis refers to the process of creating organometallic compounds, and is among the most actively researched areas in chemistry. Organometallic compounds are frequently used in fine chemical syntheses and to catalyze reactions. In situ Infrared and Raman spectroscopy are among the most powerful analytical methods for the study of organometallic compounds and syntheses.
Isocyanates are critical building blocks for high performance polyurethane-based polymers that make up coatings, foams, adhesives, elastomers, and insulation. Concerns over exposure to residual isocyanates led to new limits for residual isocyanates in new products. Traditional analytical methods for measuring the residual isocyanate (NCO) concentration using offline sampling and analysis raise concerns. In situ monitoring with process analytical technology addresses these challenges and enables manufacturers and formulators to ensure that product quality specifications, personnel safety, and environmental regulations are met.
Measuring and understanding polymerization reactions, mechanisms, kinetics, reactivity ratios, and activation energies lead researchers to employ in situ infrared spectroscopy as a routine technique to gain comprehensive, information-rich data that is used to advance research in a shorter time frame.
Knowledge of impurity kinetics and mechanism of formation is important in determining reaction end-point in chemical and process development studies. Accurate, reproducible, and representative reactions samples are necessary for these studies.
In situ chemical reaction kinetics studies provide an improved understanding of reaction mechanism and pathway by providing concentration dependences of reacting components in real-time. Continuous data over the course of a reaction allows for the calculation of rate laws with fewer experiments due to the comprehensive nature of the data. Reaction Progression Kinetics Analysis (RPKA) uses in situ data under synthetically relevant concentrations and captures information throughout the whole experiment ensuring that the complete reaction behavior can be accurately described.
Continuous flow chemistry opens options with exothermic synthetic steps that are not possible in batch reactors, and new developments in flow reactor design provide alternatives for reactions that are mixing limited in batch reactors. This can often result in better product quality and higher yield. When coupled with Process Analytical Technology (PAT), flow chemistry allows for rapid analysis, optimization, and scale-up of a chemical reaction.
Grignard reactions are one of the most important reaction classes in organic chemistry. Grignard reactions are useful for forming carbon-carbon bonds. Grignard reactions form alcohols from ketones and aldehydes, as well as react with other chemicals to form a myriad of useful compounds. Grignard reactions are performed using a Grignard reagent, which is typically a alkyl-, aryl- or vinyl- organomagnesium halide compound. To ensure optimization and safety of Grignard reactions in research, development and production, in situ monitoring and understanding reaction heat flow is important.
Hydrogenation reactions are widely used in the manufacture of both bulk and fine chemicals for reducing multiple bonds to single bonds. Catalysts are typically used to promote these reactions and reaction temperature, pressure, substrate loading, catalyst loading, and agitation rate all effect hydrogen gas uptake and overall reaction performance. Thorough understanding of this energetic reaction is important and PAT technology such as in situ FTIR, calorimetry and automated, in situ sampling in support of HPLC analysis ensure safe, optimized and well-characterized chemistry.
Highly reactive chemistry is a terminology used to describe chemical reactions that are particularly challenging to handle and develop due to the potentially hazardous and/or energetic nature of the reactants, intermediates and products that are present during synthesis. These chemistries often involve highly exothermic reactions which require specialized equipment or extreme operating conditions (such as low temperature) to ensure adequate control. Ensuring safe operating conditions, minimizing human exposure, and gaining the maximum amount of information from each experiment are key factors in successfully designing and scaling-up highly reactive chemistries.
Many processes require reactions to be run under high pressure. Working under pressure is challenging and collecting samples for offline analysis is difficult and time consuming. A change in pressure could affect reaction rate, conversion and mechanism as well as other process parameters plus sensitivity to oxygen, water, and associated safety issues are common problems.
Hydroformylation, or oxo synthesis/process, is important for the production of olefins to aldehydes and aldehydes from alkenes. Hydroformylation reactions are performed at high pressure and can be challenging to sample due to the extreme reaction conditions, as well as the toxic, flammable, and reactive raw materials and reagents.
Catalysts create an alternative path to increase the speed and outcome of a reaction, so a thorough understanding of the reaction kinetics is important. Not only does that provide information about the rate of the reaction, but also provides insight into the mechanism of the reaction. There are two types of catalytic reactions: heterogeneous and homogeneous. Heterogeneous is when the catalyst and reactant exist in two different phases. Homogeneous is when the catalyst and the reactant are in the same phase..
One of the four major classes of chemical reactions, synthesis reactions are represented by important examples in organic synthesis, catalyzed chemistry, polymerizations and inorganic/organometallic chemistry. In the simplest case, a synthesis reaction occurs when two molecules combine to form a third, more complex product molecule. Often, synthesis reactions are more complex and require a thorough understanding of the kinetics and mechanisms of the underlying chemistry, as well as carefully controlled reaction conditions.
Design of Experiments (DoE) requires experiments to be conducted under well-controlled and reproducible conditions in chemical process optimization. Chemical synthesis reactors are designed to perform DoE investigations ensuring high quality data.
Reaction mechanisms describe the successive steps at the molecular level that take place in a chemical reaction. Reaction mechanisms cannot be proven, but rather postulated based on empirical experimentation and deduction. In situ FTIR spectroscopy provides information to support reaction mechanisms hypotheses.
Organometallic Synthesis refers to the process of creating organometallic compounds, and is among the most actively researched areas in chemistry. Organometallic compounds are frequently used in fine chemical syntheses and to catalyze reactions. In situ Infrared and Raman spectroscopy are among the most powerful analytical methods for the study of organometallic compounds and syntheses.