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PROTON NMR WITHOUT DEUTERATED SOLVENTS
Team spreads the word that usable spectra can be obtained using regular organic solvents
NO D? NO PROBLEM AUTHORS have published a report on No-D NMR, a relatively simple technique that is grabbing attention.


What synthetic chemist hasn not wistfully lingered over a reaction flask, longing for a simple, informative way of following the chemistry without exposing sensitive reagents to air and moisture? AUTHORS contends that chemists already have the technology to do just that--most just haven not been using it.
AUTHORS calls the technique No-D NMR, short for no-deuterium proton nuclear magnetic resonance spectroscopy. As the name implies, the technique involves taking NMR spectra of reaction mixtures or reagent solutions in standard organic solvents, rather than protium-free solvents such as CDCl3 and CCl4 that are commonly used for NMR spectroscopy.

When they hear about his work, AUTHOR says, chemists always ask the same question: Would not the solvent peaks be so large that they swamp any signals from the product?

"That is the mental block that all of us have," AUTHOR answers, but it is just an old chemists tale. Modern NMR spectrometers are sophisticated enough to detect minor chemical components in a sea of solvents. AUTHOR says one need only expand the vertical scale of No-D NMR spectra to see that this is so. Indeed, in a No-D spectrum of phenyllithium in benzene, the ortho, meta, and para protons of the aryl lithium species can be easily distinguished from the solvent.

AUTHOR does not want to imply that this is a new concept. Scientists who study biological macromolecules routinely use a H2O/D2O mixture as an NMR solvent. And it is quite common to take the spectra of nuclei other than protons, for example, 31P and 19F, in nondeuterated solvents.

"Ten percent of the folks reading this are going to say, I have done this before, I don not see what the big deal is," AUTHOR admits. But he hopes that the report will be an eye-opener for the other 90%. "One can think about this as in situ NMR. You can do this for every reaction, if you want. In our lab, we are running No-D spectra on a daily basis."

While he emphasizes the No-D technique s utility, AUTHOR is also quick to point out that deuterated solvents are still de rigueur for characterizing final products in his lab. "I am not trying to put Aldrich or Cambridge Isotopes out of business," he jokes.

Of course, to use the technique effectively, one must master a few tricks. These, AUTHOR insists, are easy to learn, and the group wrote the paper in part to provide some guidance.

They have had the most success when a solution s concentration falls within the 0.1 to 1 M range. Solvent suppression programs can improve the spectral quality of more dilute samples.

Also, data acquisitions have to be taken with the spectrometer in the unlocked mode because, without deuterated solvents, there is no deuterium for the instrument to lock onto. AUTHOR says this isn not a problem for most modern NMR spectrometers. As long as the magnet doesn not drift substantially, running in unlocked mode should still give narrow peaks.

AUTHOR adds that the art of learning to reliably shim a No-D sample is like learning to ride a bicycle: "At the beginning, the data may not be pretty." But with a little practice, it becomes no more difficult to shim No-D samples than it is to shim an analogous deuterated sample. Shimming involves adjusting the magnetic field homogeneity to obtain narrow, well-shaped peaks.

Chemists can use a sealed reference tube of deuterated solvent as "training wheels" to lock and shim upon before acquiring data from the No-D sample. The report also includes a substantial footnote with shimming advice. "People who have just read the footnote have had tremendous success with the technique," AUTHOR says.

"As a means for monitoring reaction progress, No-D NMR complements traditional gas chromatography and thin-layer chromatography techniques because reactive intermediates, such as metal enolates, can be measured directly. No-D NMR has helped us to solve a variety of problems more quickly and cost-effectively than would have been possible from indirect methods such as traditional chemical functionalization."

The idea occurred to AUTHOR while his group was studying a high-molecular-weight polymer that carried a functional group on one end. Despite the large number of protons in the molecule, 1H NMR could still be used to observe protons near the functional group. After that, it was just a short leap to realizing that it didn not matter if those hydrogens were part of the molecule or part of the solvent.

AUTHORS say the technique is equally useful when it comes to analyzing commercially available solutions. They plan to publish a report describing how to use the technique to determine the concentration of organolithium reagents in solution



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