Purity and Yield Determination in Solid-Phase Synthesis

The further development of these methods will allow chemists to select an appropriate method on the basis of the specific SP synthetic problem in hand and the instmmentation available in their laboratory. Eventually, analytical monitoring will become a routine element of SPS, as it is in classical solution-phase organic chemistry, and one of the major bottlenecks for the further development of SPS will disappear. 

4 PURITY AND YIELD DETERMINATION IN SOLID-PHASE SYNTHESIS 

The determination of the yield of a reaction carried out in the SP and the structure and purity of the product is an essential component of the process of SPS. The same analytical methods that we examined in the previous section for reaction monitoring can be used, but their usefulness for qualitative analysis may vary, as we will describe in this section. 

The problems associated with high-throughput analysis of SP reaction products, automation of purification techniques, and automation of methods for stmcture determination in SPS are typically encountered in combinatorial chemistry and will be dealt with more thoroughly in Chapters 6-8. 

The cleavage and characterization of intermediates or final compounds, as for off-bead reaction monitoring (Section 1.3.2), are the most reliable methods to quantify the outcome of an SPS. The final target molecule on SP has to be cleaved into solution so that it can be characterized by classical off-bead methods. The synthetic intermediates obtained after each SPS step can also be characterized off-bead when the cleavage conditions do not affect their structure and when the amount of resin beads lost during the characterization process is negligible. 

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