Process NMR

Simple, Continuous Flow Hi-Resolution NMR at 60 MHz.


The use of an NMR as a simple flow detector for benchtop reaction monitoring, mixing monitoring, dilution monitoring, or conversion monitoring has been limited by the need to bring the "reaction" to the typical "supercon" NMR lab. We are introducing a continuous flow NMR system that can be on the benchtop. The system uses a high resolution 60 MHz permanent magnet with a simple flow cell and total system volumes of 2 to 5 ml depending on the length and diameter of the transfer tubing. Further, detection limits of analytes in the 200+ ppm range are possible without the use of typical deuterated NMR solvents. Analysis times of 5 to 20 seconds are also possible at flow rates of 5 to 20+ ml/minute.
Simple, Continuous Flow Hi-Resolution NMR at 60 MHz figure 1

As an example, we observed the Hydrogen bonding exchange rate between the OH protons on isopropyl alcohol with the hydrogen of water as a function of increasing water concentration. Figure 1 shows the starting spectrum (blue) of "off the shelf" 91 vol % IPA obtained at the local pharmacy flowing through the NMR at 10 ml/min. At this concentration, the IPA OH hydrogen and water hydrogen are spectrally distinct. The red spectrum is the final spectrum after 50 minutes of slowing adding water to the original IPA to bring the IPA concentration to approximately 76 vol %. At the end of the dilution, the OH peaks from IPA and water are in complete exchange as represented by the single peak.
Simple, Continuous Flow Hi-Resolution NMR at 60 MHz
Simple, Continuous Flow Hi-Resolution NMR at 60 MHz

Figure 1: "Off the Shelf" Isopropyl Alcohol at the original concentration of 91 vol % IPA (blue) and diluted to 76 vol % (red).

Figure 2 shows the results of the sequential addition of 20 0.5 ml aliquots of water that take the original 91% IPA to its final concentration of 76%. As shown in Figure 3, one can readily observe the convergence of the OH peaks as the dilution progresses.
Simple, Continuous Flow Hi-Resolution NMR at 60 MHz

Figure 2. Continuous flow NMR dilution monitoring of 91% by volume isopropyl alcohol with water to a final concentration of 76%.
Simple, Continuous Flow Hi-Resolution NMR at 60 MHz

Figure 3. Continuous flow NMR monitoring of OH hydrogen exchange between water and isopropyl alcohol as a function of IPA concentration.

Continuous Flow NMR was also used to monitor solute addition in a non-mixed vessel. In this experiment a concentrated table sugar solution (2.19 molar) was injected every 100 seconds at an injection volume of 0.083 ml each for the first 30 minutes (1 ml total) with two final injections of 0.5 ml each. Starting volume of water was 25 ml. Total volume of sugar solution injected was 2.0 ml representing 1.5 grams of table sugar. Flow rate through the NMR flow cell was 10 ml/min with a total NMR sample volume (tubing + flow cell) was 5 ml. Again, no solvent suppression was applied.

Figure 4 shows the overall spectra through the entire run. Figure 5 shows the expansion of the water/carbohydrate region showing the sensitivity of the 60 MHz flow NMR to sugar concentration.
Simple, Continuous Flow Hi-Resolution NMR at 60 MHz

Figure 4. Overall flow NMR results for concentrated sugar solution addition to water.
Simple, Continuous Flow Hi-Resolution NMR at 60 MHz

Figure 5. Water/carbohydrate region expansion showing table sugar addition to water.

For more information on reaction monitoring "on-low" with process NMR systems please contact:

John Edwards
Tel: +1 (203) 744-5905
 
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