Quantitative Determination of Resin Loading in Solid-Phase Organic Synthesis Using ¹³C MAS NMR

Abstract

The use of quantitative carbon nuclear magnetic resonance spectroscopy ((13)C NMR) for the determination of resin loadings has been investigated. Magic angle spinning (MAS) NMR spectra have been obtained for solvent-swollen resins on a conventional 7 mm CP/MAS probe using the two pulse phase modulation (TPPM) proton decoupling sequence. Loadings of resin-bound organic compounds were evaluated via addition of tetrakis(trimethylsilyl)silane as reference or using the carbon resonances of the polymeric resin material as an internal standard. Results for several functionalized Wang and trityl resins are consistent with those obtained using well-established analytical methods. The (13)C NMR method has interesting applications in the field of solid-phase organic synthesis (SPOS), since no functional group acting as a support for the attachment of a quantifiable chromophore must be available in the material of interest.

13C SPE MAS measurement of ligand concentration in compressible chromatographic beads

“…The SPE MAS NMR experiment, where the 13 C nuclei are excited by a 90° pulse and the signal is acquired under high power 1 H decoupling, preserves accuracy, and must be preferred in analytical applications. Inspired by a previous study, where resin loading in solvent swollen polymer resins for solid‐phase organic synthesis was estimated by 13 C SPE MAS NMR, we investigate here if the lower signal‐to‐noise remains sufficient or not and if accuracy can be retained in a system with soft and thereby, under MAS conditions, deformable components. We also establish and communicate protocols that may allow one to achieve experimental errors that are assumedly sufficient for a range of materials in this analytical application of solid‐state NMR spectroscopy.…”

Precision and sensitivity optimization of quantitative measurements in solid state NMR

“…However, because of the complexity of cross polarization dynamics [1], quantitative determinations achieved by CP MAS experiments are not trivial [2][3][4], and hence SPE MAS experiments are usually preferred, provided of course that sensitivity is not an issue. A few quantitative studies in the solid state have been reported so far [5], and the investigated systems have been as diverse as, for instance, drugs [6][7][8], cement based materials [9,10], soils and humic substances [11,12], coals [13] and resin loadings [14]. As a matter of fact, recent technological advances and the currently less prohibitive price of the required instrumentation have made quantitative ssNMR available to chemists and biochemists as a new analytical tool.…”

Structural characterization and quantitation of compound loading of disubstituted benzoates bound to Wang resin through high‐resolution magic angle spinning NMR spectroscopy

“…Any premature cleavage of molecules during the synthesis is easily detected by the occurrence of the methylene signal a, which belongs to the Wang linker of the free resin. It should be mentioned that other protocols for quantifying compound loading for resins containing the Wang linker, based on 13 C or 19 F NMR spectroscopy, 24,25 have been reported. However, these methods require long measurement times or the presence of a fluorine atom.…”