Following reactions and determining structures of intermediates on-bead

Following reactions and determining structures of intermediates on-bead 

Qualitative color tests are frequently used to follow reactions to assure completion. The Kaiser ninhydrin test is the best known of these [15], An improved method for the detection of secondary amines has been reported [16], The Fmoc method for assuring complete deprotection of an amine is in wide use [13], 

IR methods can be used to support a proposed intermediate in a reaction [17] or to follow the incorporation of a distinctive functional group (e.g. CHO) onto a resin [8,18], IR is especially useful for surfaces such as pins or crowns, where NMR techniques are not useful. High-quality IR spectra can be obtained from single beads [19], 

Natural abundance gel-phase 13C NMR spectroscopy is used for assessing intermediate structures in solid-phase synthesis [20], but requires long acquisition times and so is not useful for following reactions. Affymax scientists [21] have pioneered the use of specifically 13C-labeled starting materials in conjunction with fast 13C-gel phase NMR to follow multi-step reactions [17,22,23], 

Magic angle spinning (MAS) NMR brings the power of H NMR to solid-phase chemistry [2,25], A simple MAS spectrum, that of the reaction product of succinic anhydride and TentaGel S NH2, is shown in Fig. 2. Presaturation of the PEG resonance at 3.6 ppm is critical to spectral quality. The complex peaks from 3.4 to 3.9 ppm are due to residual PEG, 13C satellites and the terminal CH2 of the PEG chain. The characteristic doubling of the solution-phase CDC1, and TMS resonances can be seen. 

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