Solid-phase multi-step Polymers

Under certain condition, however, reactions are still preferably conducted in solution. This is the case e.g., for heterogeneous reactions and for conversions, which deliver complex product mixtures. In the latter case, further conversion of this mixture on the solid support is not desirable. In these instances, the combination of solution chemistry with polymer-assisted conversions can be an advantageous solution. Polymer-assisted synthesis in solution employs the polymer matrix either as a scavenger or for polymeric reagents. In both cases the virtues of solution phase and solid supported chemistry are ideally combined allowing for the preparation of pure products by filtration of the reactive resin. If several reactive polymers are used sequentially, multi-step syntheses can be conducted in a polymer-supported manner in solution as well. As a further advantage, many reactive polymers can be recycled for multiple use. 

One of the key technologies used in combinatorial chemistry is the solid-phase organic synthesis (SPOS)2, originally developed by Merrifield in 1963 for the synthesis of peptides3. In SPOS, a molecule (scaffold) is attached to a solid support, for example, a polymer resin . In general, resins are insoluble base polymers with a linker molecule attached to them. Often, spacers are included to reduce steric hindrance by the bulk of the resin. Linkers on the other hand are functional moieties, which allow the attachment and cleavage of scaffolds under controlled conditions. Subsequent chemistry is then carried out on the molecule attached to a support, until at the end of the often multi-step synthesis the desired molecule is released from the support (Figure 7.1). 

The urea-formaldehyde polymer is formed by a multi-step reaction process between urea and formaldehyde. The initial phase is a methylolation of the urea under slightly alkaline conditions with a formaldehyde-urea (F/U) molar ratio of 2.0 1 to 2.4 1. Condensation of the methylolureas from the methylolat ion reaction is at atmospheric reflux with a pH of 4 to 6. This condensation polymerization continues to a pre-determined viscosity, at which time the pH is adjusted with a suitable base to 7-3 to 8.0. The adhesive is then concentrated to a total solids content of 50 to 60 percent by vacuum distillation. Additional urea is then normally added to produce a final F/U molar ratio of 1.6 1 to 1.8 1. 

Abstract Recent developments in the microwave-assisted synthesis of heterocycles are surveyed with the focus on diversity-oriented multi-component and multi-step one-pot procedures. Both solution- and solid-phase as well as polymer-supported methodologies for the preparation of libraries of heterocycles are reviewed. Advantages of microwave dielectric heating are highlighted by comparison with conventional thermal conditions. 

As discussed in Section 16.1.4, polymer-bound acetoacetates can be used as precursors for the solid-phase synthesis of enones [30]. For these Knoevenagel condensations, the crucial step is to initiate enolization of the CH acidic component. For the microtvave-assisted enolization procedure, however, piperidinium acetate was found to be the catalyst of choice, if temperatures were kept below 130 °C. A 21-member library, of polymer-bound enones was generated (Scheme 16.33) by using a multi-vessel rotor system for parallel microwave-assisted synthesis. Reaction... 

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