Recent Advances in the Use of Polymers as Chemical Reagents

Some recent developments in the preparation of polymeric reagents and their use in various chemical reactions are described. Improved polymeric acyl transfer reagents were prepared. They possess good mechanical properties and are therefore easy to handle and pure products are obtained by their use. With one of these polymeric reagents pure peptides may be obtained in high yield in reactions lasting only 10—30 mm. Polymeric alkylating and condensing agents are described. Specific polymeric chelating agents were obtained by impregnating macroporous polymers by the appropriate chelating compounds. The use of polymers as protecting groups in synthesis is discUssed. Recent results on the simultaneous use of two different polymeric reagents for analytical and synthetic purposes are cited. The use of polymers as chemical reagents has increased greatly in recent years. The main types of polymeric reagents developed have been polymer bound catalysts (biological and non-biological), specific polymeric adsorbents for biologically active compounds and for metal ions, polymeric transfer agents and polymeric carriers for peptide synthesis and other organic syntheses.1 Polymers have also been used as immobilizing media and as means for separating different active species from each other.1 In this article some recent developments in the field of polymeric reagents will be discussed. Polymeric acyl transfer agents have been suggested as efficient reagents for peptide synthesis.2 Their use is outlined in Scheme 1. Polymeric active esters of N-blocked amino acids (III) are treated with soluble, C-blocked amino-acids or peptides. The product peptide is obtained in solution and may be separated from the reaction mixture by filtering off the polymer. An excess of the insoluble polymeric reagent III may be employed and thus high yields of products IV, V are obtained. The first polymer of type I prepared was cross linked poly(3-nitro-4hydroxystyrene). Considerable yields of peptides as long as bradykinin could be obtained by its use.3 However improved polymeric carriers were sought because of a number of disadvantages inherent to the use of the above polymeric reagents. They are powdery and are thus often difficult to filter and wash; a more convenient physical form such as beads was desirable. Some of these polymeric reagents disintegrate partially, liberating fine particles into solution; a polymer backbone more stable mechanically and chemically was needed. The above polymers are capable of swelling only in a limited number of solvents thus making the accessibility of the reactive sites very solvent dependent. A polymer possessing high accessibility irrespective of solvent or at least in a large number of solvents was sought. Reactions utilizing the above polymers were sometimes much slower than similar reactions with soluble active esters. Polymers of higher reactivity are desirable for faster reactions. The synthesis of an improved mtrophenol polymer is described in Scheme 2. The best synthetic route was found to be the Friedel—Crafts alkylation of polystyrene in bead form by 4-hydroxy-3-nitrobenzyl chloride.4 The good mechanical properties of the starting polymers (VI, commercial