ANALYTICAL TECHNIQUES FOR COMBINATORIAL CHEMISTRY - QUANTITATIVE INFRARED SPECTROSCOPIC MEASUREMENTS OF DEUTERIUM-LABELED PROTECTING GROUPS

Infrared microspectroscopy has been developed as a powerful, nondestru ctive technique for the quantitative analysis of solid-phase, resin-bo und chemical reactions. The synthesis and/or application of deuterium isotope containing protecting groups, including acetyl-d(3) chloride, benzoyl-d(5) chloride, and l-d(9))oxy]carbonyl]-oximino]-2-phenylaceto nitrile (BOC-ON-d(9)) are also introduced as highly selective infrared signatures amenable to quantitation by infrared spectroscopy. Calcula tion 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 dete rmination of chemical yields in solid-phase resin reactions involving changes in deuterium content.