Determination of enantiomeric purity from solid‐state ³¹P MAS NMR of organophosphorus compounds

Abstract

Phosphorus-31 Magic-Angle Spinning (MAS) NMR is shown to be an extremely useful and accurate method for the determination of the enantiomeric purity for chiral organophosphorus compounds. "P and "C chemical shielding tensors in racemic and enantiomeric crystals of organophosphorus compounds vary because of different crystal symmetries. This implies that solid-state 31P (13C) MAS spectra of an enantiomerically impure sample reveal separate signals from the racemic and enantiomer crystallites. Simple integration (or deconvolution) of the MAS NMR signals can thus be used to determine the enantiomeric purity of the sample. For organophosphorus compounds the application of this technique to 31P MAS NMR is of particular interest due to the high sensitivity and large shielding anisotropy of the 31P nucleus. KEY WORDS 31P MAS NMR Enantiomeric purity

Solid-State Nuclear Magnetic Resonance Spectroscopy-Pharmaceutical Applications

“…In another example, a series of racemic and optically pure organophosphorus samples were studied by solid‐state 31 P NMR spectroscopy 202. Analogous to the tartaric acid work, the two optical isomers (+ and −) had identical 31 P NMR spectra that were distinct from the spectrum of the racemic material.…”

Chiral recognition of ethers by NMR spectroscopy

“…113,[117][118][119][120] Here, further NMR parameters can be evaluated (e.g., crystal packing effects, chemical shift tensors, etc. ), which are not available from isotopic liquid phase NMR.…”

“…During the last two decades, enormous progress has been made in high-resolution solid state NMR by introduction of cross-polarization (CP) and magic angle spinning (MAS) techniques. [113][114][115][116] So, chiral discrimination by solid state NMR in no longer out of scope. Some approaches led to successful enantiodifferentiation, e.g., by isotropic chemical shift comparison exploiting the fact that conformational structures and crystal packing forces are different for solid material containing racemate or pure enantiomers, respectively.…”

“…Some approaches led to successful enantiodifferentiation, e.g., by isotropic chemical shift comparison exploiting the fact that conformational structures and crystal packing forces are different for solid material containing racemate or pure enantiomers, respectively. 113 Another technique is the application of the ODESSA (one-dimensional exchange spectroscopy by sideband alternation) pulse sequence 117 ; some racemic oxazaphosphorinanes could be distinguished from their enantiomers. 118 Finally, it is possible to differentiate stereoisomers by their chemical shift tensors, which can be extracted from the side bands in their solid-state NMR spectra.…”

NMR studies of chiral organic compounds in non‐isotropic phases

“…The existence of different types of crystals and consequently diastereotopic intermolecular interactions result in a variety of physical properties like melting point, solubilities and intermolecular distances between chemically equivalent nuclei. Hence, the crystal and/ or powdered samples of racemate and enantiomers should be easily recognized by solid state NMR spectroscopy giving observable differences of the iso- This approach has been exploited by Jacobsen and coworkers (24) for searching of chiral species of organophosphorus compounds. In a cited paper authors reported 31 P CP/MAS NMR spectra for racemic and optically active forms of the N-[(diphosphono)methyl]-3-isobutyl-thiomorpholine 2 shown in Fig.…”