ABSTRACT
In practice, gel-based, spherical resin beads of 50-200 µm diameter are commonly used in solid-phase organic chemistry (SPOC). These can be easily synthesized or bought from a range of commercial suppliers. The size, shape, and uniformity are important features, and the uniformity of cross-linked polymer particles is vital for reproducible SPOC. Robust spherical beads with a uniform size are preferred for reproducible chemistry, with irregularly shape particles being much more sensitive to mechanical destruction, often falling apart in the course of the chemistry. Bead size is also important since reaction rates are inversely proportional to bead size. The technique of suspension polymerization is almost universally used for resin synthesis and provides regular particles in a highly reproducible manner. Typically, styrene and divinylbenzene (DVB) mixtures are dispersed as spherical droplets in an excess of an immiscible phase (water) containing the polymerization initiator. The aqueous phase generally contains a low level of some dissolved suspension stabilizer, a surface-active species, which prevents the organic monomer droplets from conglomerating. In the course of the polymerization, these droplets are converted to the hard glassy beads. Then the resin particles can be collected by filtration; unreacted monomers, initiator, and other byproducts removed by solvent extraction; and the beads vacuum dried and sieved. The introduction of functionality onto a polymer support is usually achieved by direct chloromethylation to give the classical Merrifield resin. However, an alternative approach is to use a co-monomer that already bears the desired functionality in the free polymerization mixture or some precursor that can subsequently be transformed. This second strategy can be useful in producing a structurally well-defined resin network with control of functional group ratios (Fig. 1). So-called Merrifield resin and related PS-based analogues (e.g., aminomethyl resin) are the most widely used resins in SPOS today. They are characterized as being a gel-type polymer typically containing 1-2% cross-linking agent DVB which provides the links between the linear PS chains, with the whole polymer solvated and with reactions taking place throughout the polymer network, controlled by diffusion into the bead.
