Benchtop NMR spectroscopy for industry

Quality Control of raw materials in thechemical industry

Introduction – benchtop and high field NMR
spectroscopy
NMR spectroscopy is an analytical techniquefamiliar to most chemists working in industry andacademia, and is a vital part of today’s chemistry,
biochemistry, food and pharmaceuticals research.
NMR enables fast identification of most organic
substances by determining their chemical
structure and can often quantify the amount ofa specific substance in samples. Benchtop NMR
spectrometers use permanent magnets insteadof the cryogen cooled superconducting magnets
used in high field NMR. They are consequently
much smaller, easier to maintain and cheaper
to run and can take over routine work previously
carried out using high field NMR instruments
or complementary analytical techniques (e.g.
FTIR, NIR, GC-MS and some chromatography
techniques). Instruments can be placed in alaboratory or test facility and can also be moved
on a trolley to different factory locations. Thisnow makes benchtop NMR spectroscopy an ideal
technique for quality control of raw materials, forin line process monitoring and end product Quality
Assurance (QA).

1Screening Applications of Benchtop NMR
Most analytical work on benchtop NMR
spectrometers uses just the proton (1H) spectrum,
but benchtop instruments are perfectly capable ofobtaining spectra from other NMR-sensitive nuclei
including carbon (13C), fluorine (19F), phosphorus(31P), lithium (7Li), boron (11B), silicon (29Si), and manyothers. The Oxford Instruments X-Pulse instrument
offers a broadband option where a large range ofNMR-sensitive nuclei can be accessed on a single
instrument. Benchtop NMR spectrometers typicallywork best for identifying molecules or compoundswith molecular weights around 600 Daltons orless. In this range, the peaks in the spectra can bequantified by lower dispersion benchtop systems.

A common application for benchtop NMR is fast
screening of samples to confirm molecular structure
after a chemical synthesis. This provides a QA
tool, to check the quality and identity of incoming
raw materials. They can additionally check large
numbers of samples quickly to see whether theexpected peaks are present in the spectrum before
passing the samples on to high field systems formore detailed analysis. This saves a considerable
time for the chemists doing the syntheses andmakes sure that the expensive high field instruments
are used in the most efficient way.
We highlight below case study examples of QA
screening from chemical suppliers to the (1) plastics
and construction, (2) fluoropolymers and (3) lithium
battery industries.

Raw materials checking (1) – fibreglass sizing compounds.
In this example, a company making fibreglass was concerned about the quality of incoming chemicals used
for glass fibre sizing. They used an Oxford Instruments X-Pulse instrument to test three different samples,
each provided by two suppliers.

A570

2B570
16.5

6.0

5.5

5.0

4.5

4.0

3.5
3.0
1H (ppm)

2.5

2.0

1.5

1.0

0.5

0.0

Figure 1 - Comparison of spectra of sample type 570, from suppliers A and B

The user compared samples from the two suppliers that were supposed to be the same material. First,
sample type 570 (Figure 1, above). Clearly the two spectra are identical, proving that the materials fromSupplier A and Supplier B are the same.

2A560

2B560
16.0

5.5

5.0

4.5

4.0

3.5

3.0
1H (ppm)

2.5

2.0

1.5

1.0

0.5

0.0

Figure 2 - Comparison of spectra of sample type 560, from suppliers A and B
We see the same with spectra from sample type 560, as in Figure 2 (above). Again, the two spectra areidentical, proving that the materials from Supplier A and Supplier B are the same chemical.

A550

2B550
1

6.0

5.5

5.0

4.5

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3.5

3.0

2.5

2.0
1H (ppm)

1.5

1.0

0.5

0.0

-0.5

-1.0

-1.5-2.0

Figure 3 - Comparison of spectra of sample type 550, from suppliers A and B
However, when we compare the spectra from sample type 550 (Figure 3, above) we can immediately seethat the spectra are NOT the same, proving that the material from one of the suppliers is not the correctmaterial.

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Raw materials checking (2) – fluorinated chemical
feedstocks.
In this example, a chemical manufacturer received afeedstock chemical from two different suppliers andfound that one of them worked in their reaction but
the other didn’t, costing the company a significant
amount in both time and money. They wanted toknow if the cause of if this was due to degradation,
contamination, or another factor.

The feedstock chemical was 2,3-Dichloro-1,1,1trifluoropropane, a relatively simple moleculethat generates a surprisingly complex 1H NMR
spectrum given that it has only three hydrogenatoms. We first looked at the 1H spectrum of areference sample of this material and comparedthat to the spectrum of the “failed” material. Figure
4 shows the two spectra.

Figure 4 - 1H 1D NMR spectra of 2,3-Dichloro-1,1,1-trifluoropropane (bottom, red) and theunknown sample (top, blue).

It is clear that there are big differences between the two spectra, so we can tell immediately that the reason
for the failure of the reaction is that this supplier’s feedstock is chemically different from what was claimed.
To confirm this conclusion, we then looked at the 19F spectra which is extremely straightforward to interpretand again saw very large differences between them, as shown in Figure 5.

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By looking also at the 13C spectra (not shown here) we were able to identify that the “failed” material wasin fact 3-Chloro-1,1,1-trifluoropropane and not 2,3-Dichloro-1,1,1-trifluoropropane and was mislabelled.
Because the full structural determination is not necessary to screen a compound, either the 1H or the 19F
spectra alone can provide the yes/no QA answer. Both can be acquired in approximately 1 minute enabling afast and, when needed, high throughput checking process.

Figure 5 - 19F 1D NMR spectra of 2,3-Dichloro-1,1,1-trifluoropropane (bottom, red) and theunknown sample (top, blue), now assigned as 3-Chloro-1,1,1-trifluoropropane.
Final product checking (1) – Electrolytes for Lithium
ion batteries
In this case study, a chemical manufacturer had
two different batches of their final product, a typicalbattery electrolyte of lithium hexafluorophosphate(LiPF6) in a mixture of two carbonated solvents, ethyl
methyl carbonate (EMC) and ethylene carbonate(EC). Although to the eye the two batches B1 andB2, looked identical it was found that batch B2 hadvery different performance characteristics to those
expected when place inside a battery cell. As withthe previous examples, initially the 1H spectra of thetwo compounds were collected. The spectra bothshow all the expected peaks for the 1H nuclei in thetwo solvents as identified in figure 6. Visually, they
appear identical. Again, as with the previous example

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the next test was to measure the 19F spectrum, inthese samples this will specifically probe the Li-salt
and will identify if the source of the performancedifference can be found there. When comparing
the spectra in figure 7, the difference is immediatelyapparent. In sample B2 the expected doublet fromthe PF is also accompanied by a second doublet.
This doublet most likely corresponds to OPF(OH), a
common breakdown product of LiPF6 when exposed
to water in the presence of carbonated solvents.
This clearly identifies the cause of the performancedifference between the two electrolytes.

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8.0

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4.0
1H (ppm)

3.5

3.0

2.5

2.0

1.5

1.0

0.5

0.0

Figure 6 - 1H Spectra of two different batches of LiPH6 in EMC/ECConclusions
In the examples presented, similarities and differences in the “good” and “bad” spectra can be spotted with thenaked eye, and without any knowledge of the chemical structure of the compounds. This enables “Go - No Go”
test methods for incoming raw materials that can be formalised with spectral pattern matching to reference
databases.

21Probable breakdown product

-40

-45

-50

-55

-60

-65

-70

-75
19F (ppm)

-80

-85

-90

-95

-100

-105

-110

-115

Figure 7 - 19F Spectra of two different batches of LiPH6 in EMC/EC, extra peaks in sample
B2 clearly show the failed sample
For many QA/QC and raw materials screening applications, especially for low molecular weight molecules,
modern benchtop NMR spectrometers now provide a faster, more convenient and low-cost solution. They
can replace or complement analytical methods such as GCMS, FTIR and chromatography as well as more
complex, expensive high field NMR instruments. Their speed and simplicity of use creates significant cost andtime savings for both low volume and high throughput uses.

6X-Pulse is a high-resolution benchtop NMRspectrometer. Using a high stability 60MHz (1.4T)
permanent magnet X-Pulse enables users to collect
NMR data without the need for liquid cryogens or
specialist facilities. X-Pulse has been optimised withunique shimming technology to provide resolution of
better than 0.35Hz. For convenience, X-Pulse uses
standard 5mm NMR tubes requiring only 300μL ofsample. X-Pulse is the first benchtop NMR system
to have a broadband X-Nuclei channel allowing
users to select the nucleus that is right for their own
application including, carbon, phosphorous, lithium,boron, silicon and many more.
X-Pulse is controlled by the user friendly spinflow
software interface. This software allows users tocontrol every aspect of the instrument. For quality
control applications like those described above
specific experiments can be stored and run using
a single mouse click to ensure repeatability andconsitancy between measurements.

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