Low cross-linked polystyrene

Low cross-linked polystyrene resins (1% divinylbenzene) is probably the most popular solid support. These resins swell to 2-6 times their original volume depending on the solvent used. Swollen resin, after removal of solvent and without excessive drying, remains in a rubbery state and can be easily flattened for FTIR study in the transmission mode. The support-bound compound should be washed free of reagent and solvent. 

Low cross-linked polystyrene resins were first adopted for oligodeoxyribonucleo-tide synthesis within the framework of the phosphodiester method [146-150],... 

In the following paragraph a description is given for the preparation of very low cross-linked polystyrene gel, which can hardly be obtained on the market. 

A method for the polymerization of polysulfones in nondipolar aprotic solvents has been developed and reported (9,10). The method reUes on phase-transfer catalysis. Polysulfone is made in chlorobenzene as solvent with (2.2.2)cryptand as catalyst (9). Less reactive crown ethers require dichlorobenzene as solvent (10). High molecular weight polyphenylsulfone can also be made by this route in dichlorobenzene however, only low molecular weight PES is achievable by this method. Cross-linked polystyrene-bound (2.2.2)cryptand is found to be effective in these polymerizations which allow simple recovery and reuse of the catalyst. 

The pore structure of most cross-linked polystyrene resins are the so called macro-reticular type which can be produced with almost any desired pore size, ranging from 20A to 5,000A. They exhibit strong dispersive type interaction with solvents and solutes with some polarizability arising from the aromatic nuclei in the polymer. Consequently the untreated resin is finding use as an alternative to the C8 and Cl8 reverse phase columns based on silica. Their use for the separation of peptide and proteins at both high and low pH is well established. 

The separation takes place in a column of sulphonated cross-linked polystyrene resin, which is a strong cation exchanger. The matrix of the resin is strongly anionic in nature (S03 ) and at the low pH used initially, the amino acids will be positively charged and will be attracted to the negatively charged sulphonate groups. 

A third variation on this theme was recently reported by Hodge (48), who alkylated the cinchona alkaloids on the quinuclidine nitrogen using the well-known chloromethylated cross-linked polystyrenes. Optical yields were low (10 to 30%) and no significant conclusions were drawn. 

Moderate doses, between 1.0 and 20 Mrad (10 to 200 kGy) on partially or completely formed articles and polymer pellets substantially reduce the content of residual monomer98 The mechanical properties of polystyrene are changed only at high radiation doses, which is characteristic of low cross-link yield and glassy morphology.99... 

In this section the use of polystyrene and copolymers of styrene with various cross-linking agents as supports for solid-phase organic synthesis is discussed. Copolymers of styrene with divinylbenzene are the most common supports for solid-phase synthesis. Depending on the kind of additives used during the polymerization and on the styrene/divinylbenzene ratio, various different types of polystyrene can be prepared. However, non-cross-linked polystyrene has also been used as a support for organic synthesis [10,16-22], Linear, non-cross-linked polystyrene is soluble in organic solvents such as toluene, pyridine, ethyl acetate, THF, chloroform, or DCM, even at low temperatures, but can be selectively precipitated by the addition of methanol or water. 

Catalyzed aldol additions do not generally proceed with high diastereoselectivity at ambient temperature. Improved stereoselectivity can be achieved by using preformed, diastereomerically pure enolates at low temperatures (Entry 5, Table 7.2). This strategy enables the solid-phase preparation of stereochemically defined polyketides. On cross-linked polystyrene, the observed diastereoselectivity in the addition of boron enolates to aldehydes is the same as that in the homogeneous phase reaction [14,18]. 

The most common synthesis of sulfonic esters, which can also be conducted on insoluble supports, is the sulfonylation of alcohols with sulfonyl chlorides under basic reaction conditions. Several examples of the sulfonylation of support-bound alcohols and of the reaction of support-bound sulfonyl chlorides with alcohols have been reported (Table 8.11). For the preparation of highly reactive sulfonates, bases of low nucleophilicity, such as DIPEA or 2,6-lutidine, should be used to prevent alkylation of the base by the newly formed sulfonate. This potential side reaction is, however, less likely to occur on cross-linked polystyrene than in solution, because quaternization on hydrophobic supports only proceeds sluggishly (see Section 10.2 and [155]). 

Cross-linked polystyrene can be directly nitrated with fuming nitric acid at low temperatures (-25 °C to 0°C) [189,203,374] polymers with up to one nitro group per arene result [203]. Partial nitration can be achieved with milder nitrating agents, such as acetyl nitrate [203]. Because direct nitrations are not compatible with most linkers (which are often acid- or oxidant-labile), nitro compounds are generally not prepared on supports but in solution, and are then linked to the support. 

Phthalazine-l,4-diones have been prepared by nucleophilic cleavage of polystyrene-bound phthalimides (Entry 7, Table 15.27). The reaction rate proved to be highly dependent on the solvent used, being low in EtOH but high in DCM. Using DMF as solvent, no phthalazinediones could be isolated [325]. Hexahydropyridazines have been prepared on cross-linked polystyrene in low yields by treatment of support-bound 1-acyloxy-l, 3-dienes with diimide [326]. 

Obviously, the way to heterogeneous enantioselective catalysis is open when chiral ligands are introduced into the polymers. This idea was first proposed by Okamoto and Still (231). However, the first catalytic results were published by Cazaux and Caze (235). These authors use the asymmetric Mo(VI) complex (9) covalently bound to a cross-linked polystyrene resin for the enantioselective epoxidation of geraniol. Unfortunately, the enantiomeric excess obtained was low—far below that obtained with the Ti-tartrate catalyst (Section II,B). Moreover, the polymeric structure appeared to be unstable. 

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