Cycle time as a variable in CRAMPS NMR. Detection of minor impurities in solids to levels of ≤0.01 mol%

The use of varying multiple-pulse decoupling cycle times in homonuclear dipolar decoupling experiments with combined rotation and multipole-pulse spectroscopy proton nuclear magnetic resonance (NMR) is shown to be capable of quantitatively and qualitatively analyzing amounts of occluded residual liquid solvent, present as saturated solution, in some organic solids crystallized from solution. Lower limits of detection can be 0.01 mol%, as illustrated for the cases of durene,p-hydroxy benzoic acid, and adipic acid crystallized from ethanol, and alanine crystallized from water. Quantitative detection at this level depends upon the phase diagram of the system in question, and the ability to obtain a high-resolution proton NMR spectrum from that portion of the sample consisting of the occluded solvent impurity in the presence of a relatively large proton background from the probe. Determinations of spin diffusion may be used to infer the average size of the mobile domains containing the impurity. The variation of longitudinal relaxation time with temperature may be used as a check on the uniformity of saturated solvent occluded in the system studied. The classical case of using a cooling curve to detect the total amount of liquid protion remaining in the crystal after crystallization is discussed.