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7.4. CONCLUSION 241
Wavenumber (cm'"*) b
Figure 7.11. UV-Visible absorption of 9-anthroylnitrile in the supernatant (A) and single-bead FTIR spectra taken from the resin (B) before and after a 20-min reaction.
aldehydes and ketones has been developed.9 Hydroxyl groups are routinely quantitated by reaction with 9-anthroylnitrile for 20 min in DMF14; Figure 7.11 shows the UV-visible spectra of 9-anthroylnitrile in the supernatant and the single-bead IR spectra of the solid sample before and after a 20-min reaction. Similarly, carboxyl groups are routinely quantitated by reaction with 1-pyrenyldiazomethane for 50 min in ethyl acetate. In general, these methods take about 1 h or less and require 2-10-mg resin samples.
“Cleave-and-analyze” methods can be used in solid-phase organic syntheses, but direct spectroscopic analyses are convenient and sometimes provide
242 VIBRATIONAL SPECTROSCOPY
information that would be hard to obtain in any other way. The IR spectral shifts and peak-area changes can be used to observe intermediates in solid-phase syntheses. Single-bead FTIR spectroscopy, for instance, is a simple, sensitive, fast, and convenient method for following reactions on a solid support without stopping them or cleaving product from the resin. Single-bead FTIR can also provide kinetic information. Fourier transform FTIR internal reflection spectroscopy in the micro- and macro-formats is now the primary analytical method for monitoring of reactions directly on surface-functionalized polymers.
Dye-coupling/consumption techniques enable quantitation of functional groups on resin. However, this area is at an early stage of refinement; more quantitative analytical methods for quantifying a diverse set of organic functional groups are required.
The author is very grateful to co-workers at Novartis for participating in the projects described and to the co-authors in references 3a, 3b, 4c, 9, lOa-c, and 11-14. In particular, the author thanks Lina Liu, Robert Dunn, Qing Tang, Qun Sun, Wenbao Li, and Roger E. Marti for their contributions.
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