FTIR Spectroscopy

Fourier Transform Infrared (FTIR) spectroscopy is an analytical technique used to understand the structure of individual molecules and the composition of molecular mixtures. The fundamental vibrations of molecules occurs at the same frequency as infrared light. Molecules can absorb this light and convert it into molecular vibration. FTIR spectrometers allow us to monitor this absorption and as every molecule vibrates slightly differently, a unique infrared spectrum can be obtained.

The bands seen within a spectrum correspond to a particular vibration. Therefore, we can use the position (frequency) of these bands to identify specific molecular bonds. The intensity of the bands tells us how much light is absorbed, this is directly proportional to the number of bonds that are vibrating.  

FTIR spectroscopy has broad use and applicability in the analysis of molecules important in the pharmaceutical, chemical and polymer industries. FTIR spectroscopy equipment is used in industry and academic laboratories to better understand reaction kinetics, reaction mechanism and pathways as well as catalytic cycles. In QA/QC labs. FTIR spectroscopy is used to help scale-up chemical reactions, optimize reaction yield and minimize impurities. In the chemical industry, FTIR spectroscopy is used to ensure that raw materials, intermediate compounds and final products meet content and purity specifications. In chemical product production, FTIR spectroscopy helps to ensure that processes are stable, in control, and meet end-product specifications and impurity profiles. 

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To measure materials in situ the infrared light from the spectrometer needs to be immersed or in contact with the chemistry. To achieve this, ATR (Attenuated Total Reflectance) has been developed into an immersion probe design that allows for a wide variety of reactor and flow interfaces.

ATR FTIR is an attractive technology since it only involves insertion of the probe into the reactor (or flow stream), collect spectra in real time under real reaction conditions, even in aqueous-based chemistry (due to the small path length of the ATR, ~14um). Additionally, bubbles, solids such as catalysts do not effect the measurement.

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:

• Epoxides
• Alkylation Reactions
• Polymerization Reactions
• High Pressure Reactions
• Hydrogenation Reactions
• Hydroformylation or Oxo Synthesis/Process
• Grignard Reaction Mechanisms
• Halogenation
• Biocatalysis | Enzymatic Catalysis
• Flow Chemistry
• Catalyzed Reactions
• Chemical Synthesis

In many instances, reaction understanding requires the construction of accurate reaction profiles for each species that are expressed as concentration versus time, leading to the determination of reaction kinetics, as well as detection of intermediate(s), reaction initiation and endpoint. In-Situ FTIR Spectroscopy, such  such as ReactIR, is an ideal technique to provide this information, as it allows the rapid collection of detailed reaction profiles in real time.

In-Situ FTIR Spectroscopy brings a couple of advantages to reaction analysis. First, the use of the fingerprint region of the mid-infrared enables the individual tracking of chemical species, which in turn provides clues to the mechanism of the reaction. Second, Beer's Law gives the connection between the measured absorbance of the reaction species and its concentration. This relationship means we can use an offline measurement to determine the concentration of an offline sample, and then use that data point to scale the mid-infrared profile. There is a correlation between the concentration measurement of offline samples and the in-situ measured component profiles.

Mid-infrared Attenuated Total Reflectance (ATR) technology offers numerous advantages over alternative analytical methods, including other molecular spectroscopy techniques.  Researchers and scientists improve chemical development by leveraging these advantages, including:

• Immersible for direct insertion into reaction vessel for in situ, continuous, real-time measurements
• No extractive sampling required, providing the ability to measure chemistry in its natural environment
• Impervious to bubbles or solids, making it ideal for hydrogenations or any heterogeneous reactions
• Suitable for aqueous chemistry
• Non-destructive, preserving the integrity of the chemical reaction
• Adheres to Beer-Lambert law, enabling both qualitative and quantitative measurements

Instantaneous information can be gained about a reaction from FTIR spectroscopy because it is an in-situ technique.  This is a key benefit to obtaining further insights into reaction behavior, particularly where transient species are involved.

The reason why the data is so important is because of its continuous nature. With ATR FTIR Spectroscopy equipment, data collection is automated, typically generating qualitative or quantitative information every minute, even as fast as four times every second. This means that rather than running a large number of reactions to understand rate dependencies, just a few experiments can provide the necessary information to determine the driving forces of a reaction supporting reaction mechanism, critical control parameters and "fingerprinting" of the reaction that can be seamlessly transferred to production. This means that research can progress at an accelerated rate. In addition, the data is often more accurate than data analyzed by offline techniques as there is no possible alteration of the molecules by preparation for analysis, or by exposing it to an environment other than that within the reaction vessel.

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 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 (e.g. 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, endpoint, and product stability of biphasic and colloidal reactions

FTIR Spectroscopy is used in the pharmaceutical, chemical, and petrochemical industries as well as in academic research.

• Chemical Synthesis
• Grignard Reactions
• Hydrogenation Reactions
• Crystallization and Recrystallization
• Asymmetric Catalysis
• Halogenations
• Enzymatic Catalysis
• Cross-Coupling Reactions
• Organometallic Chemistry
• Solution Phase and Heterogeneous Catalysis

• Intermediates
• Surfactants
• Flavors and Fragrances
• Coatings/Pigments
• Agrochemicals
• Initiators
• Bulk Chemicals
• Isocyanate Chemistry
• EO/PO
• Highly Oxidizing Reactions
• Hydroformylation
• Catalytic Reactions
• Phosgenations
• Esterifications
• Epoxides
• Alkylations

• Metal-Mediated Chemistry
• Catalysis
• C-H Activation
• Mechanistic Studies
• Reaction Kinetics

The ReactIR 702L is the first system that truly merges the power of real-time, in situ FTIR 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 offers flexibility to deploy ReactIR in various locations across the lab. An “always on“ detector reduces set up 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.

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 FTIR spectroscopy to provide comprehensive information and rich experimental data that to advance their research.

Featured FTIR Spectroscopy Citations

• Mei, C., Deshmukh, S., Cronin, J., Cong, S., Chapman, D., Lazaris, N., Sampaleanu, L., Schacht, U., Drolet-Vives, K., Ore, M., Morin, S., Carpick, B., Balmer, M., & Kirkitadze, M. (2019). Aluminum Phosphate Vaccine Adjuvant: Analysis of Composition and Size Using Off-Line and In-Line Tools. Computational and Structural Biotechnology Journal, 17, 1184–1194. https://doi.org/10.1016/j.csbj.2019.08.003
• Meng, S. S., Lin, L. R., Luo, X., Lv, H. J., Zhao, J. L., & Chan, A. S. C. (2019). Aerobic oxidation of alcohols with air catalyzed by decacarbonyldimanganese. Green Chemistry, 21(22), 6187–6193. https://doi.org/10.1039/c9gc02446h
• Rao, K. S., St-Jean, F., & Kumar, A. (2019b). Quantitation of a Ketone Enolization and a Vinyl Sulfonate Stereoisomer Formation Using Inline IR Spectroscopy and Modeling. Organic Process Research & Development, 23(5), 945–951. https://doi.org/10.1021/acs.oprd.9b00042
• Beutner, G. L., Young, I. S., Davies, M. L., Hickey, M. R., Park, H., Stevens, J. M., & Ye, Q. (2018). TCFH–NMI: Direct Access to N-Acyl Imidazoliums for Challenging Amide Bond Formations. Organic Letters, 20(14), 4218–4222. https://doi.org/10.1021/acs.orglett.8b01591
• Rehbein, M. C., Husmann, S., Lechner, C., Kunick, C., & Scholl, S. (2018). 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, 95–100. https://doi.org/10.1016/j.ejpb.2017.09.013