Application example

One of the easiest ways of monitoring a reaction’s conversion with ReactIR is to pick a characteristic peak of the starting material. At the start of your experiment, ReactIR measures the full spectrum of your starting material, and you can select which peak you wish to monitor.

After you start your experiment, ReactIR will measure the spectrum of the reaction mixture periodically, zoom in on your selected peak, and create a 3D diagram of the intensity change of that peak over time (Scheme 1). The white peak on the left disappears, while a new peak gradually appears on the right, which belongs to the product.

 

Scheme 1: 3D diagram of the selected peak’s intensity change vs reaction time

 

ReactIR can turn this 3D diagram into a 2D plot, showing the peak intensity with respect to reaction time (Scheme 2). This allows you to see the conversion of your starting material into your product.

 

 

Scheme 2: Turning your 3D IR spectrum into a reaction conversion diagram

 

The main advantage of this technique lies in its solvent subtraction option, which allows even extremely low intensity peaks to become visible. This method isolates the peaks of substrates and products, which would normally seem to be just minor perturbations superimposed upon the solvent’s spectrum (see scheme 3).

 

 

For example, we have successfully used this method to monitor the conversion of 5-nitroindole into 5-aminoindole in ThalesNano’s PhoenixTM+H-Genie® flow reactor system.

 

On Scheme 4, you can see the power of solvent subtraction, as well as the change of the selected peak over time. On the solvent subtracted spectrum, you can see that at first, no peak was detected, because the reactor system needed to reach steady state. Because the nitroindole needs time to reach the detector, no starting material was detected in the first few minutes. After the starting material reached the IR instrument, the characteristic peak of the nitro group at ~1335 cm-1 was detected.

 

Scheme 4: Detecting the conversion of nitroindole into aminoindole

 

As hydrogen gas was gradually injected into the liquid flow, after a few minutes we started to detect the decrease of the intensity of our selected peak. We waited for the steady state to stabilize, but because we still saw the nitro group peaks, we changed the conditions in our reactor system. After a few minutes, a further decrease in peak intensity was observed. At this point, we finished the experiment without further optimization. The increasing peak intensity at the end is due to washing our system with methanol at a higher flow rate, which resulted in all the remaining nitroindole in the system to arrive at the detector at almost the same time.

The 3D spectrum was converted into a 2D conversion diagram using ReactIR’s software (Scheme 5), which also allows you to add comments to the diagram. All the major events and important changing points are demonstrated on our diagram as well.

 

Scheme 5: 2D conversion diagram of our reduction reaction

 

Conclusion: We were able to monitor the conversion of 5-nitroindole into 5-aminoindole using Mettler Toledo’s ReactIR 702L instrument, at a low (0.05M) concentration of the starting material in methanol. The method is perfectly suitable for reaction optimizations, as you can continue to change the parameters in situ, and detect the changes in-line shortly after. This method can be continued until an acceptable conversion is observed.

Note: quantification of the conversion into a percentage value is also possible based on the 2D diagram using Beer-Lambert law, but this is not discussed here in detail.