Analytical Techniques for Combinatorial Chemistry: Quantitative Infrared Spectroscopic Measurements of Deuterium-Labeled Protecting Groups

Infrared microspectroscopy has been developed as a powerful, nondestructive technique for the quantitative analysis of solid-phase, resin-bound chemical reactions. The synthesis and/or application of deuterium isotope containing protecting groups, including acetyl- d 3 chloride, benzoyl- d 5 chloride, and 2-[[[( tert -butyl- d 9 )oxy]carbonyl]oximino]-2-phenylacetonitrile (BOC-ON- d 9 ) are also introduced as highly selective infrared signatures amenable to quantitation by infrared spectroscopy. Calculation of first derivative carbon−deuterium (C−D) stretching absorbance relative to resin backbone derivative absorbances provided pathlength-independent quantitation of deuterium content and allowed for the determination of chemical yields in solid-phase resin reactions involving changes in deuterium content.