Polymeric Supports in Organic Synthesis

The polymer support used in these reactions should have a reasonably high degree of substitution of reactive sites. In addition, it should be easy to handle and must not undergo mechanical degradation. There are several polymers in use, but the most common one is the styrene-divinyl benzene copolymer. 

Because of the tetrafunctionality of divinyl benzene, the polymer shown is a three-dimensional network that would swell instead of dissolving in any solvent. These polymers can be easily functionalized by chloromethylation, hydrogenation, and metalation. For example, in the following scheme, an organotin reagent is incorporated  

Because the cross-linked polymer molecule in Eq. (1.7.1) has several phenyl rings, the reaction in Eq. (1.7.2) would lead to several organotin groups distributed randomly on the network polymer molecule. 

Sometimes, ion-exchanging groups are introduced on to the resins and these are synthesized by first preparing the styrene-divinyl benzene copolymer [as in Eq. (1.7.1)] in the form of beads, and then the chloromethylation is carried out. Chloromethylation is a Friedel-Crafts reaction catalyzed by anhydrous aluminum, zinc, or stannous chloride the polymer beads must be fully swollen in dry chloromethyl methyl ether before adding the catalyst, ZnCla. Normally, the resin has very small internal surface area and the reaction depend heavily on the degree of swelling. This is a solid-liquid reaction and the formed product can be shown to be 

This reaction is fast and can lead to disubstitution and trisubstitution on a given phenyl ring, but monosubstitution has been found to give better results. The 

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Vinyl polymers incorporating acrylamide, ethylene-maleic anhydride, styrene-maleic anhydride, maleimide, etc. have also been prepared and functionalized to serve as polymeric supports in organic synthesis (Table 2-7). 

PEGs are one of the most used soluble polymeric supports in organic synthesis. They are well soluble in water and many organic solvents, such as alcohols, dimethyl formamide, toluene, dichloromethane, and acetone, but are insoluble in... 

Dendritic polymeric supports or hybrids of these with solid-phase resins are among the most promising candidates for new high-loading supports in organic synthesis and catalysis. However, every new polymeric support has to compete with the current bench mark, the so-called Merrifield resin and its derivatives. 

Baxendale, I.R., Storer, R.I. and Ley S.V. (2003) Supported reagents and scavengers in multi-step organic synthesis, in Polymeric Materials in Organic Synthesis and Catalysis (ed. M.R. Buchmeiser), VCH, Berlin, pp. 53-136. 

R. I. Storer and S. V. Ley. Polymeric materials in organic synthesis and catalysis. In M. R. Buchmeiser, Ed. Supported Reagents and Scavengers in Multi-step Organic Synthesis. VCH, Berhn, 2003, p. 53. 

Suspension polymerization was applied to prepare polynor-bomene aosslinked beads suitable for use as supports in organic synthesis. The monomers used included norbor-nene, norbom-2-ene-5-methanol, and aosslinking agents including bis(norbom-2-ene-5-methoxy)alkanes, di(norbom-2-ene-5-methyl)ether, and l,3-di(norbom-2-ene-5-methoxy) benzene. The initial resins, which were unsaturated, were subsequently modified using hydrogenation, hydrofluorination, chlorination, or bromination to yield saturated resins with varying properties. They were reported to be superior to more traditional styrene-divinylbenzene resins due to reduced interference in electrophilic aromatic substitution reactions (e.g., Friedel-Crafts acylation and nitration). 

Multi-phase Systems.—An account of the use of insoluble polymer supports in organic synthesis has been given by Leznoff The use of alumina, an inorganic polymeric support, in organic reactions has been reviewed by Posner/ A new monograph on phase-transfer catalysis is available " and a comparison of phase-transfer catalysis by quaternary ammonium salts, crown ethers, and poly-alkylamines has been made. ... 

E. C. Blossey and D. C. Neckers, Eds., Solid Phase Synthesis, Halsted, New York, 1975 P. Hodge and D. C. Sherrington, Eds., Polymer-Supported Reactions in Organic Synthesis, Wiley-Interscience, New York, 1980. A comprehensive review of polymeric protective groups by J. M. J. Frechet is included in this book. 

Standard Suspension Polymerization Techniques, Appendix (1980). In Polymer-Supported Reaction in Organic Synthesis (P. Hodge and D. C. Sherington eds.), Wiley Chichester. 

Solid-state synthesis of /J-nitrostyrenes has been reported by Varma et al. in a process that uses readily available styrene and its substituted derivatives and inexpensive clay-supported nitrate salts, clayfen and clayan (Scheme 6.50) [170], In a simple experiment, admixed styrene with clayfen or clayan is irradiated in a MW oven (-100-110 °C, 3 min) or heated in an oil bath (-100-110 °C, 15 min). For clayan intermittent heating is recommended with 30-s intervals to maintain the temperature below 60-70 °C. Remarkably, the reaction proceeds only in solid state and leads to the formation of polymeric products in organic solvent. 

Perhaps the most important issues to consider now are the application of novel methodologies, molecular diversity, and synthetic convenience. There have been several reports of novel, one-pot procedures for the preparation of 1,2,4-triazoles with diverse structures. Synthesis of 1,2,4-triazoles on polymeric supports, in both solution and solid phase, represents a step toward the combinatorial synthesis of these heterocycles. It is these novel applications of technology to organic synthesis that perhaps lead the way in 1,2,4-triazole chemistry. 

Soluble polymers that have been used in hquid-phase methodologies are listed in Fig. 5.1 [3, 7, 8, 34, 35]. Polyethylene glycol and non-cross-linked polystyrene are some of the most often used polymeric carriers for organic synthesis and have found frequent use in the preparation of soluble polymer-supported catalysts and reagents consequently, a brief discussion of these polymers is warranted. 

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. 

The solid-phase synthesis of organic compounds requires a linkage element which acts as a tether to the polymeric support. In a multi-step synthesis the linker must be stable towards all reaction conditions used, but should easily and quantitatively be cleaved to release the target molecule without any degradation of the latter. 

The use of polymeric reagents or catalysts is popular in organic synthesis. Usually, the reactive entity is attached to a solid support, and while its chemical properties are similar to its solution counterpart, the heterogeneicity of the solid supported version... 

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