Running Experiments Without Using Deuterated Solvents

Introduction

The No-D NMR (No-Deuterium Proton NMR) technique is a measurement of high resolution 1H NMR spectra without using a deuterium solvent. With this technique many reaction mixtures or reagent solutions are directly available using protonated solvents. In conventional NMR measurements, 2H signals of deuterium solvent are used for shimming, however 1H solvent signals work just as well in No-D NMR measurements. Since suppression of strong 1H solvent signals by the WET pulse suppression sequence eliminates 13C satellite signals, it is a convenient approach to collect 1H NMR spectra without deuterium solvent by No-D NMR measurement.


Merits of No-D NMR with More Solvent Choice

  • The better approach for newly synthesized unstable compounds
  • Follow reactions and dynamic processes:
    • Go from flask to NMR tube and back again, no sample prep, no additional reagents added
    • Neat samples
    • Broadband nuclei
  • Use solvents with better solubility
  • Use solvents with desired properties (polarity, protic/aprotic, boiling/freezing point, etc.)
  • Substitute "green" solvents when possible
  • Protonated solvents are much less expensive
  • It's so EASY!
    • Quickly obtain high-quality results
    • Easily implemented in undergraduate lab, research, or QC environment
    • Can collect useful 1D and 2D data

Automation script for No-D NMR

1H spectra of 5 mg rotenone measured with JNM-ECZ500R

The following 5 steps are constitute the automated No-D NMR measurement procedure for JEOL's Delta software. All the usual manual measurement parameters are automatically adjusted.

  1. Shimming
  2. Detecting solvent signals
  3. Suppression of solvent signals
  4. Processing FID data
  5. Chemical shift adjustment

Using the Delta software, whereas chemical shifts for conventional 1H measurement require NMR lock (Fig. 1a) for shimming, for the automated No-D NMR the adjustment for chemical shifts occurs automatically using fast 1H gradient shimming (Fig. 1b). Its result has the same chemical shift information as a deuterated solvent sample spectrum (Fig. 1c). Gradient shimming works at different temperatures, in different solvents, however, varying sample heights is not a problem.

Because the total acquisition time in the 2nd dimension as well as the time steps between the samples are kept the same, the spectral width and resolution are identical to the uniformly sampled data.

For starting No-D NMR measurement, only simple 2 parameters are required

Operation window of No-D NMR

As shown in Fig. 2

  1. Select the solvent so that unwanted peak(s) can be excluded by digital filtering
  2. Input the number of suppression signals

Application of No-D NMR 1: Observation of exchangeable 1H signals

When the compound with the exchangeable proton is dissolved in an exchangeable proton solvent (D2O, CD3OD, etc.), the proton is replaced with a deuterium atom. As a result, it is not possible to observe amino protons for the target molecule (Fig. 3 upper). On the other hand, the exchangeable proton can be observed in No-D NMR, since amino protons are not replaced while dissolved in a protonated solvent (Fig. 3 bottom).

2.5mg L-Tryptophan measured with JNM-ECZ600R


Application of No-D NMR 2: Apply to mixed solvent

Because No-D NMR can suppress multi-site signals, it is also effective for multi-signal solvents such as CH3OH and mixed solvent samples. Furthermore, 13C decoupling is useful, when solvent 13C satellite signals overlap with sample signals. Fig.5 indicates how a sample signal can be distinguished from a 13C satellite by 13C decoupling. Chemical shifts in Fig.4 and Fig.5 are intentionally adjusted for better clarity.

2.5mg ibuprofen (racemic form) measured with JNM-ECZ400S

Conclusion

No-D NMR is a cost effective way to collect NMR data for process NMR applications, undergraduate laboratories, and research laboratories. There is also an opportunity to use "green" solvents instead of the "usual" organic solvents. Shimming, solvent suppression, and referencing can be automated using proton gradient shimming, which is robust and fast. Using the Wet suppression pulse sequence is easy to automate and very effective, while referencing is possible from a solvent peak. Unfortunately, the use of No-D NMR can still be problematic due to solvent/sample peak overlap. There is a need to choose solvents carefully and in some cases peak overlap is ultimately unavoidable. However, deuterated solvents do not pose overlap problem.



No-D NMR Is Included In Delta. To Download A Free Copy, Please Visit nmrsupport.jeol.com.
 

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Relevant Publications

3 SEP
2020

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