Despite the focus on the use of solid-phase techniques
for the synthesis of combinatorial libraries, there have been few examples where
libraries have successfully been made and screened in solution.
The benefit of preparing libraries on resin beads has been explained as offering advantages in handling, especially where a need to separate excess reagents from the reaction products is attached to the resin. In most of case a simple filtration effects a rapid purification and the product are ready to further synthetic transformation. But it should be remember that using solid phase chemistry brings several disadvantages as well. Clearly the range of chemistry available on solid phase is limited and it is difficult to monitor the progress of reaction when the substrate and product are attached to the solid phase.
Indeed some groups have expressed a preference for solution libraries because there is no prior requirement to develop workable solid phase coupling and linking techniques. The difficulty in purifying large number of compounds without sophisticated automated processes.