A watched pot never boils….how to monitor reactions the easy way

When monitoring reaction progress for determination of reaction kinetic parameters, NMR spectroscopy has increasingly become the method of choice. The ease in which one can calculate the concentration changes of a substrate being consumed or a product being formed over time, directly from peak integration are the reason behind this. However, from the user endpoint, acquiring the necessary NMR data can sometimes be a cumbersome and complicated endeavor, particularly if the reaction is not amenable to be performed in an NMR tube. Some examples of the challenges one can encounter are, sampling the reaction at the appropriate intervals, being able to access the NMR instrument for the necessary periods of time or at exactly the right time intervals, making sure all acquisition parameters are kept the same between runs, etc.

Enter the NMReady-flow! As Toby showed us on his earlier post from April, ^[1] the NMReady-60 family of spectrometers can be readily converted into online analyzer. Here is a very cool video in which Dr. Juan Araneda shows us how easy of a process this really is.^[2]

With the aid of a simple peristaltic pump now we can easily set up a regular reaction system and attach it to our NMR, making the acquisition of NMR spectra for kinetic data analysis a true benchtop, no-hassles involved endeavor!

We have evaluated several different reactions using the NMReady-flow^[3] but my favorite by far is the hydrosilation of acetophenone catalyzed by tris(pentafluorophenyl)borane (figure 1), but this is mainly due to my biased love of Boron chemistry and main group catalysts!

Figure 1. Hydrosilation of acetophenone with triphenylsilane catalyzed by tris(pentafluorophenyl)borane

One of the highlights of this example in particular is that the reaction was carried out in regular non-deuterated dichloromethane. Figure 2 displays the stacked spectra that were obtained while monitoring the reaction with the NMReady-60e adapted with the NMReady-flow. The parameters employed for the acquisition were: continuous flow, ¹H NMR at 59.96 MHz, No. of scans: 16, flow rate: 1.2 mL/min.

Figure 2. Stacked spectra acquired with the NMReady-60e while monitoring the hydrosilation of acetophenone.

As we can see from the stacked spectra in figure 2, the signal for the non-deuterated solvent dominates. However, we can easily zoom-in into the desired regions for analysis (figure 3), where we can follow both the formation of our hydrosilated product (with the increase on the signal for its methyl group at 1.5 ppm), or the consumption of the acetophenone starting material (with the decrease of the signal for its methyl group at 2.6 ppm).

Figure 3. Integration regions employed for monitoring both the consumption of the acetophenone and the production of the hydrosilated product. The signals followed correspond to the methyl groups in each compound respectively.

With the integration data at hand we can easily calculate the respective concentrations for both reactant and product and we can then generate our plot of concentration vs. time Graph 1.

Graph 1. Concentration vs time for the consumption of acetophenone and the production of (1-phenylethoxy)triphenylsilane in the hydrosilation of acetophenone monitored via 1H NMR spectroscopy with the NMReady-60e and the NMReady-flow.

With the concentration data at hand we can obtain the rate of the reaction over time. In this case, the reaction is first order with respect to acetophenone as we obtain the best linear fit when we use the Ln[acetophenone] vs time in our analysis (graph 2, eqn. 1 and 2).

Eqn 1.

Eqn 2.

Graph 2. Ln[acetophenone] vs. time.

From the equation for the linear regression we can obtain the value for our rate constant k = 1.14 x10^-3s^-1. This is in excellent agreement to the published data obtained in a high field instrument.^[3]

I believe that the NMReady-60 benchtop NMR spectrometers are ideal for reaction monitoring and reaction kinetic studies as they streamline the process and facilitate data acquisition. If you would like to see more examples on reaction monitoring with the NMReady-60 you can find some more on our latest Applications Note on hydrogenation reactions.^[4]

References

^[1]www.nanalysis.com/nmready-blog/2017/3/28/process-nmr-future-key-elements-in-the-world-of-process-analytical-technology-pat [Viewed June 26/17]
^[2]www.youtube.com/watch?v=d7bPECyD-UM [Viewed June 26/17]
^[3]Parks, D.J.; Piers, W. E. J. Am. Chem. Soc., 1996, 118(39), 9440-9441
^[4]static1.squarespace.com/static/5707ede0d210b8708e037a1e/t/ 58dbd5fa46c3c49f850883c3/1490802172210/online-benchtop-NMR-flow-hydrogenations.pdf [Viewed June 26/17]