Poly supports chloromethylation

With the above background of selective catalysis a number of attempts have been made to develop analogous polymer-supported systems. Chiellini and his coworkers have used linear poly(4-vinylpyridine) partially quaternised with a chiral alkylbromide as a phase transfer catalyst in the ethylation of phenylacetonitrile. Unfortunately, the high chemical yield achieved was accompanied by a negligible enantiometic excess. However, the same group have prepared chiral catalysts by reaction of linear poly(4-chloromethyl-... 

Even in solution the relative rigidity of the polymer support can play a significant role in the reactivity of attached functional groups. Contrasting studies conducted with chloromethylated derivatives of poly(arylene ether sulfone) (Tg 175°C), phenoxy resin (Tg= 65°C) and polystyrene (Tg= 105°C) allow evaluation of chain rigidity effects. We have shown that the rates of quaternization of chloromethylated poly(arylene ether sulfones) and phenoxy resin deviate from the anticipated second order process at... 

The oxazolidine-2,5-dione heterocycle, perhaps better known as the N-carboxyanhydride of an amino acid, has been incorporated employing a modification of chloromethylated poly(styrene) (192) (76USP3985715). The reaction sequence involved utilization of a masked amino acid, ethyl acetamidocyanoacetate (205). The amino acid was liberated in a subsequent hydrolysis/decarboxylation step (Scheme 98). The cyclized, IV-carboxyanhydride-functional resins (206) were reported to be useful in solid phase peptide synthesis and as supports for enzyme immobilization. 

On stirring at room temperature ozonides of terminal alkenes (prepared in dichloromethane at — 70 °C) with a polymer-supported tertiary amine obtained from chloromethylated poly(styrene/divinylbenzene) and piperidine, followed by filtration and concentration under reduced pressure, the products (aldehydes or ketones) can be obtained easily in almost pure form in high yields <2003T493>. However, yields are low for cycloalkenes because apparently they form monomeric and polymeric ozonides. 

In another approach, reactive monodisperse porous poly(chloromethylstyrene-co-styrene-co-divinylbenzene) beads have been employed for the preparation of chiral HPLC packings. Thus, reactive chloromethyl groups were derivatized to yield amino functionalized beads onto which both rt-basic and rt-acidic type chiral. selectors, (/ )- -(l-naphthyl)ethylamine and (/ )-A -(3.5-dinitrobenzoyl)phenylglycine, respectively, were attached. The resulting chiral particles were chromatographically tested for the enantioseparation of model SAs. Despite the presence of strongly competitive it-TT-binding sites of the styrenic support these chirally modified beads afforded baseline separations for 2,2,2-trifluoro-l-(9-anthryl) ethanol and Af-(3.5-dinitro-benzoyl) leucine enantiomers, respectively [369. ... 

In a subsequent study, the Co coordinated assembly was grafted onto a cross-linked poly(glycidoxypropylmethacrylate) (GMA)-ethylene glycol dimethacrylate (EDMA) support surface. The template and Co ions were then leached out from the matrix. This surface grafted polymer exhibited turnover, Michaelis-Menten kinetics and mechanisms such as inhibition by tosyl phenyl alanyl chloromethyl ketone and inhibition on acetylation of hydroxyl group of 2-hydroxyethylmethacry-late (HEMA), similar to native chymotrypsin. 

Besides the classical polymer introduced by Merrifield (1%-crosslinked chloromethylated polystyrene), a broad variety of polymeric supports is available for SPPS and some of the most popular resins are summarized in Table 1. The chemical structures of some selected resins are presented in Figure 1 and electron micrographs of several examples are displayed in Figure 2. In addition to the solid supports listed in Table 1, there are several other carriers used in peptide synthesis such as the gel-type and macroporous poly(meth-acrylates), coated surfaces like polystyrene films on polyethylene (PEt) sheets, polystyrene-coated polyethylene or polytetrafluoroethylene, and modified glass surfaces. (For recent reviews on polymeric carriers see refs . )... 

Usual attachment of the first amino acid unit to the chloromethylated poly-styrene-divinylbenzene resin has been improved, for example, with Boc-Asn, by-condensing the amino acid (2.0 mmoles) in DMF with triethylamine (1.8 mmoles) during one day at room temperature. Cleavage of the peptide end product from the polymer as the amide derivative has been accomplished using ammonia in DMF in a sealed reaction vessel at room temperature for 5 days. A careful stud - of several peptide bond-forming reagents and polymer supports in respect to racemization has revealed the DCCI procedure to be far inferior to DCCI-NHS or EEDQ. With the model tripeptide Gly-Ala-Leu (racemization assessment by means of the Izumiya procedure), the product was found to... 

These polymers constitute the largest group to be discussed in this report and this is mainly because polystyrene and poly(chloromethylstyrene), often crosslinked with divinylbenzene, continue to be widely used in the preparation of functional polymers and resin-supported reagents. In fact most of the examples given here refer to the preparation of functional polymers rather than to new materials. This is a rapidly growing area of polymer chemistry and it is not possible to refer, in a compressed review of this nature, to all reports of functionalized styrene-based resins that have appeared in the past two years. This section falls naturally into three parts the first deals with styrene polymers and copolymers, the second with reactions on chloromethylated polystyrenes, and the third deals with styrene-related polymers. 

Another study of polymer-supported crown ethers prepared by the reaction poly(ethylene or propylene glycols) with crosslinked chloromethylated polystyrene is presented by Warshawsky et al. [6]. In Fig. 5 the structure of these crown ether polymers is shown. 

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