Impurity Detection in Solid-Phase Organic Chemistry: Scope and Limits of HR MAS NMR

We evaluate the possibilities and limits of HR MAS NMR to detect and quantify side products during solid-phase synthesis, using a model system where pyroglutamate and glutamate are coupled in a well defined ratio. Resins swollen in deuterated and protonated solvent are studied. Use of the LED sequence eliminates the peaks due to the use of protonated solvents, but sensitivity is decreased, and differential losses of magnetization might lead to a biased population estimation. However, as all sample workup steps are eliminated, this technique will be helpful in detecting minority species in solid-phase combinatorial chemistry, and its application at the different steps of the reaction might lead to the early detection of otherwise unidentifiable active components.