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.