Solid-phase extraction is widely used in bio- or environmental analyses in order to enrich or discover organic molecules from complex aqueous matrices. It can also be very useful for the purification of combinatorial libraries. There are rather simple desktop instruments available which are designed for this application -Zymark Benchmate™, Gilson Aspec™, and Hamilton Microlab™ - in addition to integrated devices in automated systems (e.g. Chemspeed); simple self-constructed systems have also been reported . One of the big advantages of solid-phase extraction is the availability of various solid phases for the separation of diverse molecules, which range from hard and soft anion or cation exchangers to reversed phase silica columns which are all available in prepacked formats. One disadvantage of the system is that the separation problem has to be evaluated very carefully to achieve optimal results. This becomes a problem when the library is diverse in terms of biophysical behavior and limits the universality of this methodology. An example of the successful application of solid-phase extraction is the synthesis of 225 basic amines which were adsorbed on an acidic ion exchanger. Neutral side products were eluted, and after several washing steps the products were cleaved using ammonia in methanol . Another example is the separation of a library containing neutral compounds from basic and acidic side products via inline solidphase extraction using ion exchangers. The neutral products were not affected by the solid phases and only side products were absorbed. Excess isocyanates were also successfully removed by trapping them as ureas using an excess of a basic amine. This side product was then efficiently absorbed to an acidic solid-phase ab sorber . An enormous increase in the versatility of this methodology can be achieved with scavenging reagents. Scavenging reagents offer the opportunity to use chemical reactivity as a mode of irreversible absorption to a solid support. This allows the selective and efficient removal of many excess reagents. Examples are the removal of excess electrophiles such as acid chlorides, sulfonic chlorides, and isocyanates as well as the trapping of excess nucleophiles such as amines . Despite these simple separation problems rather complex multistep transformations have been performed using this separation technique . Several of these polymer-supported reagents are commercially available . Furthermore, solidphase reagents prepacked in columns or microplates would be a great advantage in performing parallel reactions.
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