Merrifield resin chloromethyl polystyrene

In the case of the benzyloxytrityl-hydroxylamineresin 24b, the starting material is the Merrifield resin, chloromethylated polystyrene (1.7 mmol Cl x g 1) which is treated with 3 equiv. of 4-hydroxy-methyl benzoate in DMA with sodium methylate as base. The Beilstein test is used for monitoring and microanalyses showed the absence of chloride (Scheme 6). 

Smith and Liu have successfully prepared an unsymmetrical analog of a Katsui-type salen ligand possessing a hydroxyalkyl group in the 6-position, which facilitated the formation of an ester Hnkage to a polystyrene carboxyl chloride resin (Figure 5.19) derived from Merrifield s resin (chloromethylated polystyrene,... 

Materials. Crosslinked polystyrene beads were purchased from Bio-Rad Laboratories and were dried under vacuo at 40 C. Merrifield resin (chloromethyl group content 0.9 meq/g) was purchased from Pierce Chemical Co. A series of 3-nitro-4-acyloxy-benzoic acids ( ) were prepared by methods described in the literature. The long-chain p-nitrophenyl ester substrates were purchased from Sigma Chemical Co. p-Nitrophenyl acetate was a product of Pierce Chemical Co. and sublimed in vacuo before being used. Polystyrene (average MW 22,000) was purchased from Aldrich Chemical Co. 

Starting from the corresponding hydroxymethyl-benzocrown, it has been possible to generate the immobilized system (186) by reacting the above precursor with chloromethylated polystyrene (which is available commercially as Merrifield s resin). Typically, systems of this type contain a polystyrene matrix which has been cross-linked with approximately 1-4% p-divinylbenzene. In one study involving (186), a clean resolution of the alkali metal halides was achieved by HPLC using (186) as the solid phase and methanol as eluent (Blasius etal., 1980). In other studies, the divalent alkaline earths were also separated. 

Chloromethyl polystyrene (Merrifield resin) has been prepared by chloro-methylation of polystyrene [23,27,53,54], by copolymerization of 4-chloromethylsty-rene with styrene [20,26,55,56], and by chlorination of poly(4-methylstyrene) [57,58], Aminomethyl polystyrene is most conveniently prepared by direct amidomethylation of polystyrene with (hydroxymethyl)amides or (halomethyl)amides under acidic conditions followed by hydrolysis [59-62], but it has also been prepared directly from chloromethyl polystyrene ([63,64] see also Section 10.1.1.1). 

NaHC03 (0.2 g) was added to a suspension of chloromethylated polystyrene-1 % divinylbenzene copolymer (Merrifield resin, 0.5 g, 0.76 mmol/g) in DMSO (3 mL). After stirring for 7 h at 155 °C, the resin was washed successively with H20, MeOH, DMF, CH2C12, and Et20 and then dried under reduced pressure. To confirm the conversion of the chloromethyl resin into the aldehyde resin, two analyses were used FTIR analysis showing the typical carbonyl absorption at 1700.5 cm-1 and microanalysis showing the absence of any chlorine on the resin. The benzaldehyde resin (1.0g, 0.59mmol/g) was suspended in... 

This reaction, which is comparable to a Friedel-Crafts Alkylation, is useful for the preparation of chloromethylated arenes (for example, the Merrifield resin based on polystyrene) from the parent arene with formaldehyde, HC1, and ZnCl2. 

In early studies on insolubilized systems, Grubbs and Kroll (35) found that when chloromethylated polystyrene beads, Merrifield resins (38), were treated... 

The solid support is a special polystyrene bead in which some of the aromatic rings have chloromethyl groups. This polymer, often called the Merrifield resin, is made by copolymerizing styrene with a few percent of p-(chloromethyl)styrene. 

The chemical steps involved in the Merrifield s peptide synthesis using chloromethylated polystyrene is outlined in scheme 1. After the incorporation of the first amino add to the polymer through a benzyl ester linkage, the terminal amino group is deprotected under conditions which do not cleave the resin-amino add ester bond. 

The Merrifield resin, polystyrene-g-chloromethyl, or Wang resin can also be used as the polymeric substrate in the current invention. 

The chloromethylated polystyrene resin used for Merrifield solid-phase peptide synthesis is prepared by treatment of polystyrene with chloromethyl methyl ether and a Lewis acid catalyst. Propose a mechanism for the reaction. 

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 . )... 

The asymmetric alkylation of glycine derivatives is one of the most simple methods by which to obtain optically active a-amino acids [31]. The enantioselective alkylation of glycine Schiff base 52 under phase-transfer catalysis (PTC) conditions and catalyzed by a quaternary cinchona alkaloid, as pioneered by O Donnell [32], allowed impressive degrees of enantioselection to be achieved using only a very simple procedure. Some examples of polymer-supported cinchona alkaloids are shown in Scheme 3.14. Polymer-supported chiral quaternary ammonium salts 48 have been easily prepared from crosslinked chloromethylated polystyrene (Merrifield resin) with an excess of cinchona alkaloid in refluxing toluene [33]. The use of these polymer-supported quaternary ammonium salts allowed high enantioselectivities (up to 90% ee) to be obtained. 

Modifications of these basic materials include the formation of the V-methanesu 1 tonate 36 which has been used for the synthesis of boronates used in allyl transfer reactions39 (Section D. 1.3.3.3.) and the attachment of the compounds to a chloromethylated polystyrene (Merrifield resin)40. The immobilized amino alcohol has been used as a catalyst for the addition of zinc alkyls to carbonyl compounds (Section D. 1.3.1.4.). 2,/ -Unsaturated dihvdrooxazoles have been prepared from such amino alcohols by reaction with imino ethers41 and used as chiral dienophiles in Diels-Alder reactions (Section D. 1.6.1.1.1.2.2.1.1.). 

Solid supports ultimately require a functional group, e.g., an amino, hydroxyl, chloromethyl, or other functionality, that can be a starting point for SPPS. In some cases, a suitable functionalized monomer is included in the polymerization mix that gives the final support. Alternatively, the desired functional group can be introduced by a postpolymerization transformation [15]. The classic example of functionalization of a solid support is the chlo-romethylation of cross-linked polystyrene to produce chloromethyl-resin, also known as Merrifield resin [31]. This may then be modified further to introduce other functional groups such as aminomethyl or hydroxymethyl... 

The solid supports used are often derived from chloromethylated polystyrene resins, which can be used directly (Merrifield) for alkylation or for coupling via a linker, which may be cleavable selectively, by acid or base (e.g. Wang). 

Amberlite XAD-4 polystyrene was supplied by Rohm Haas (20-50 mesh spheres) and was dried in a rotary evaporator at 50°C for 12 hr before being chloromethylated by the procedure of Pepper etal. [71a], to give a chlorine content of 10-11% (Aldrich also supplies a chloromethylated polystyrene which is a 1 and 2% crosslinked copolymer—called Merrifield s peptide resin and containing 1 meq Cl/gm resin [72]. 

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