FTIR Spectroscopy with In Situ Reaction Monitoring

In Situ FTIR Spectroscopy with ReactIR

for Stable, Scaleable, Consistent Process Development

FTIR Spectroscopy enables scientists to measure reaction trends and profiles in real-time, providing highly specific information about kinetics, mechanism, pathways, and the influence of reaction variables on performance.  Using ReactIR in situ FTIR spectroscopy, ReactIR directly tracks reactants, reagents, intermediates, products and by-products as they change during the course of the reaction.  ReactIR provides critical information to scientists as they research, develop and optimize chemical compounds, synthetic routes, and chemical processes.

FTIR Spectroscopy Simplified

In order to understand chemical reactions, chemists must address the following:

• When does the reaction start? When does the reaction stop?
• What are the reaction kinetics and mechanism?
• What is the effect of those transient intermediates?
• Did it react as expected? Did any by-products form and why?
• What happens if reaction temperature, dosing rates, mixing rates change?

In order to get to the best data and analyze reactions quickly, there are five areas that ReactIR FTIR Spectroscopy leverages so that reaction understanding is available for every chemist – expert or not.

Best-in-Class Performance

From probe to detector to software, ReactIR is optimized for use in the mid-IR “fingerprint” region – resulting in a highly-sensitive system for fast and accurate molecular information.

One Click Analytics

Designed specifically for time-resolved reaction analysis, iC IR software combines a peak picking algorithm with functional group intelligence to drastically reduce analysis time. Users combine knowledge of their chemistry with an automated data analysis workflow to ensure correct collection and interpretation for every experiment.

Broad Range of In Situ Probes for FTIR Spectroscopy

Probes designed to operate from low to high temperature, low to high pressure, under acidic, basic, caustic, oxidizing and aqueous conditions enable the analysis of virtually any type of chemistry.

FTIR Spectroscopy Solutions From Lab to Plant

Small enough to fit in a fume hood, ATEX rated to fit in a plant, and sampling technology to sample any reaction or process - ReactIR FTIR spectroscopy can be used to prove that what happens in the plant is what you observed in the lab.

Extensive FTIR Spectroscopy Experience

As a company, METTLER TOLEDO has over 30 years of dedicated reaction analysis experience. This is our focus and our passion. We built this expertise into fit-for-purpose FTIR spectroscopy.

Process Chemistry with FTIR Spectroscopy

Featuring presenters from Boehringer-Ingelheim, AbbVie, and the University of California-Merced, this free online event is for Process Chemists and Chemical Engineers interested in learning more about how data-rich experimentation has a direct impact on the delivery of stable, scalable, and consistent processes. Each presenter will share data-rich examples that influenced their work and what it means for the future of development laboratories. 

Case studies in this seminar utilize In Situ FTIR Spectroscopy as part of their chemical and process understanding.

Why Choose Real-Time, In Situ FTIR Spectroscopy Over Offline Analysis?

Traditionally, to obtain reaction information, samples are taken for offline analysis using HPLC.  For chemistries in which sample removal results in the loss of key information, or are toxic or otherwise hazardous, this procedure is not straightforward.  Furthermore, chemists must be present to take the sample and then wait for the results before reaction analysis can begin.

These problems have implications, including:

• The sample may not be representative
• Destruction of intermediate leads to incorrect pathway hypothesis
• Poor understanding for air sensitive, toxic, explosive or pressurized systems
• Longer development times due to erroneous data because reaction changed
• Critical events that impact product or process quality may be missed

Introducing the ReactIR 702L, the first system that truly merges the power of real-time, in situ FTIR reaction analysis with equivalent operational convenience. ReactIR is ready for every chemist and for every experiment.

ReactIR is Ready to Run Overnight!
ReactIR 702L uses solid-state cooling technology to deliver best-in-class performance without the need for liquid nitrogen. By eliminating hazardous setup and repetitive Dewar refills, scientists can easily monitor chemistry over extended periods.

ReactIR is Ready to Grab and Go!
Small, stackable units save valuable space in the fume hood and offer flexibility to deploy ReactIR in various locations across the lab. An “always on“ detector reduces setup time and enables scientists to start collecting data with confidence at a moment‘s notice.

ReactIR is Ready for Your Chemistry!
Probe- and flow-based sampling technologies enable scientists to study liquid and gas phase chemistry in batch or continuous setups. Fit-for-purpose materials of construction make data collection straightforward in acidic and corrosive environments across a wide range of temperatures and pressures.

FTIR Spectroscopy Applications

ReactIR FTIR Spectroscopy works in a wide-range of chemistries in which the molecule is infrared active, the chemistry is in solution or off-gas, and the concentration is higher than ~0.1%. 

Common FTIR Spectroscopy application areas include:

FTIR versus Raman Spectroscopy

A Comparison

Although FTIR Spectroscopy and Raman Spectroscopy are often interchangeable and give complimentary information, there are practical differences that influence which one will be optimal. Most molecular symmetry will allow for both FTIR and Raman activity. In a molecule that contains a center of inversion, IR bands and Raman bands are mutually exclusive, i.e. the bond will either be Raman active or it will be IR active but it will not be both. One general rule is that functional groups that have large changes in dipoles are strong in the IR, whereas functional groups that have weak dipole changes or have a high degree of symmetry and no net dipole change, will be better seen in Raman spectra.

Choose FTIR Spectroscopy when:

• Reactions in which reactants, reagents, solvents and reaction species fluoresce
• Bonds with strong dipole changes are important, e.g., C=O, O-H, N=O
• Reactions in which reagents and reactants are at low concentration
• Reactions in which solvent bands are strong in Raman and can swamp key species signal
• Reactions in which intermediates that form are IR active

Choose Raman when:

• Investigating carbon bonds in aliphatic and aromatic rings are of primary interest
• Bonds that are difficult to see in FTIR , i.e., 0-0, S-H, C=S, N=N, C=C etc
• Examination of particles in solution is important, e.g., polymorphism
• Lower frequency modes are important, e.g., metal-oxygen
• Reactions in aqueous media are investigated
• Reactions in which observation through a reaction window is easier and safer, e.g., high pressure catalytic reactions, polymerizations
• Investigating lower frequency lattice modes is of interest
• Investigation of reaction initiation , end point and product stability of biphasic and colloidal reactions

This paper presents five examples taken from recent journal articles in which in situ FTIR spectroscopy accomplishes tasks that would be difficult, impossible, or overly time consuming, if carried out with traditional offline techniques:

• Reveal Reaction Mechanisms - Transient Intermediate Detection in a Coupling Reagent
• Monitor Difficult to Sample Chemistry - Lithiation Reaction Performed at -70 °C
• Track Reaction Progress for Better Yield & Purity - Determination of Optimal Reaction Endpoint
• Eliminate Hold Time to Increase Quality & Throughput - Decomposition Leading to Epimerization
• Quickly Determine Kinetics - 1st Order Reaction Kinetics in One Experiment

FTIR Spectroscopy in Recent Journal Publications

Continuous measurements from infrared spectroscopy are used for obtaining reaction profiles to calculate reaction rates. A list of publications from peer-reviewed journals focuses on exciting and novel applications of in situ FTIR spectroscopy.  Researchers in both academia and industry employ in situ mid-FTIR spectroscopy to provide comprehensive information and rich experimental data that to advance their research.

Featured FTIR spectroscopy citations

• Beutner, G., Young, I., Davies, M., Hickey, M., Park, H., Stevens, J., Ye, Q., “TCFH−NMI: Direct Access to N‑Acyl Imidazoliums for Challenging Amide Bond Formations”, Org. Lett. (2018) 20, 4218−4222.
• Sheikh,N., Leonori,D., Barker,G., Firth,J., Campos,K., Meijer, A., O’Brien,P., Coldham,I., “An Experimental and in Situ IR Spectroscopic Study of the Lithiation−Substitution of N-Boc-2-phenylpyrrolidine and -piperidine: Controlling the Formation of Quaternary Stereocenters” J. Am. Chem. Soc.( 2012) 134, 5300−5308.
• Hamilton, P., Sanganee, M., Graham, J., Hartwig, T., Ironmonger, A., Priestley, C., Senior, L., Thompson, D., Webb, M., “Using PAT To Understand, Control, and Rapidly Scale Up the Production of a Hydrogenation Reaction and Isolation of Pharmaceutical Intermediate”, Org. Process Res. Dev. (2015) 19, 236−243.
• Chanda, A., Daly, A., Foley, D., LaPack, M., Mukherjee, S., Orr, J., Reid, G., Thompson, D., Ward, H., “Industry Perspectives on Process Analytical Technology: Tools and Applications in API Development”, Org. Process Res. Dev. (2015) 19, 63−83.
• Rehbein, M., Husmann, S., Lechner, C., Kunick, C., Scholl, S., “Fast and calibration free determination of first order reaction kinetics in API synthesis using in-situ ATR-FTIR”, European Journal of Pharmaceutics and Biopharmaceutics 126 (2018) 95–100.