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 quanti fy side products during solid-phase synthesis, using a model system where p yroglutamate and glutamate are coupled in a well defined ratio. Resins swol len in deuterated and protonated solvent are studied. Use of the LED sequen ce eliminates the peaks due to the use of protonated solvents, but sensitiv ity is decreased, and differential losses of magnetization might lead to a biased population estimation. However, as all sample workup steps are elimi nated, this technique will be helpful in detecting minority species in soli d-phase combinatorial chemistry, and its application at the different steps of the reaction might lead to the early detection of otherwise unidentifia ble active components. (C) 2000 Elsevier Science Ltd. All rights reserved.