Polystyrene, chloromethyl derivatives

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 polymer-bound catalysts A-C. (Table 31) are prepared by reaction of the corresponding amino alcohols with partially chloromethylated 1 -2% cross-linked polystyrene. In the case of A, the enantioselectivity of the addition of dialkylzincs to aldehydes is higher than with the corresponding monomeric ephedrine derivatives (vide supra). Interesting insights into the mechanism of the alkylation of aldehydes by dialkylzinc reagents can be obtained from the experi-... 

Benzylic quaternary phosphonium and ammonium salts are dealky-lated by mild heating and/or nucleophilic anions, particularly iodide (9) and thiolate (10), but also hydroxide (11). Most N-benzyl-pyridinium or quaternary aryl ammonium compounds are particularly susceptible (12). Decompositions of this sort have seriously limited the usefulness of solid phase-transfer catalysts derived from (chloromethyl)polystyrene (13, 14). 

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,... 

We synthesized 8 by the one-step reaction of [Ph4(Tl -C4CO)]Ru(CO)3 with benzyl chloride. In contrast to previous alcohol racemization catalysts, 8 was stable in the air during racemization [30]. The racemization was performed even under 1 atm of molecular oxygen. Thus, alcohol DKR was for the first time possible with 8 in the air at room temperature (R)-l-phenylethyl acetate (99% yield, greater than 99%e.e.) was obtained from 1-phenylethanol by using 4mol% of 8, CALB and isopropenyl acetate in the presence of potassium phosphate (Scheme 1.22). This catalyst system was effective for both benzylic and aliphatic alcohols. The synthetic method for 8 was applied to the preparation of a polymer-bound derivative (9). Hydroxymethyl polystyrene was reacted with 4-(chloromethyl)benzoyl chloride to... 

By analogous fashion to imidazoline synthesis (Section 1.11.4.2.2), oxazolines have been introduced by modification of an acrylonitrile-containing polymer with ethanolamine (75JAP(K)75160392). In another modification (Scheme 99), chloromethylated polystyrene) (192) was treated with a Iithiated oxazoline (207) derived from reaction of 2-methyloxazo-Iine and butyllithium (78MI11106). The oxazoline groups were incorporated, in this study, as intermediates to carboxyl groups. 

Chloromethyl polystyrene can be converted to a free-radical initiator by reaction with 2,2,6,6-tetramethylpipcridinc-/V-oxyl (TEMPO). Radical polymerization of various substituted alkenes on this resin has been used to prepare new types of polystyrene-based supports [123]. Alternatively, cross-linked vinyl polystyrene can be copolymerized with functionalized norbornene derivatives by ruthenium-mediated ringopening metathesis polymerization [124],... 

Acid-labile linkers are the oldest and still the most commonly used linkers for carboxylic acids. Most are based on the acidolysis of benzylic C-O bonds. Benzyl esters cleavable under acidic conditions were the first type of linker to be investigated in detail. The reason for this was probably the initial choice of polystyrene as an insoluble support for solid-phase synthesis [13]. Polystyrene-derived benzyl esters were initially prepared by the treatment of partially chloromethylated polystyrene with salts of carboxylic acids (Figure 3.3). 

Various thiamine derivatives were prepared on polymer support and were tested in C-C coupling reactions.40 The most straightforward approach was the alkylation of substituted 1,3-thiazoles with chloromethyl polystyrene resin yielding supported thiazolium chloride salts. Alternatively, resin-supported thiamine derivatives were constructed in a two-step process by alkylation of the primary alcohol with chloromethyl polystyrene followed by alkylation of the ring nitrogen yielding resin 12 (Fig. 8). Not only does this pathway introduce a spacer between the active thiamine... 

Several solid supports have been employed for the attachment of o-iodosobenzoic acid, including silica gel, titania and nylon [89]. Two polymer-supported o-iodoxybenzoic acid reagents have recently been reported. The first was obtained by attaching a carboxymethyloxy derivative of f-butyl o-iodo-benzoate to an aminopropylated silica gel and oxidation with oxone [90]. The second involved chloromethylated polystyrene which was coupled with methyl 5-hydroxy-2-iodobenzoate and eventually oxidized by Bu4NS05H/MeS03H [91]. Some of these polymeric reagents appear in Scheme 31. 

In 1985, application of this simple dendritic construction to a polymer core, specifically chloromethyl functionalized polystyrene was reported. 139 Another example of the identical procedure was reported 140 except utilizing another polymeric core backbone, derived from a functionalized vinyl ether monomer. These are very early examples of dendritic comb macromolecules. 

Subsequently D Alello developed the polystyrene-hased resin in 1944 (4). Two years later, polystyrene anion-exchange resins made hy chloromethylation and amination of the matrix were produced. Four principal classes of ion-exchange resins were commercially availahle by the 1950s. These are the strong-acid, strong-hase, and weak-hase resins derived from styrene-divinylbenzene copolymers, and the weak-acid resins derived from cross-linked acrylics. To this day, the most widely used ion exchangers are synthetic organic polymer resins based on styrene- or acrylic-acid-type monomers as described by D Alelio in U.S. Patent 2,3666,007. 

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. 

The cationic polymer 40, prepared from chloromethylated polystyrene and 1, was subjected to ion-exchange to give the hydroxide or fluoride derivatives, and used in the asymmetric addition of 6 to 7 giving (S)-8 in 27% ee (Fig. 6) [36]. 

In resins where the linker is anchored by an ether bond, the ether plays an essential role as an electron-donating substituent, thereby enhancing the acid sensitivity of the linker. In many cases, such as the Wang [8] (1) and Sasrin [10] linkers (3), this ether is benzylic as it derives from chloromethyl polystyrene (8). With such resins, there is always the risk that during the cleavage reaction the benzylic ether may also cleave, resulting in a product modified or contaminated... 

When the Cu(II) complex of cyclen (AE) was attached to cross-linked polystyrene, the proteolytic activity of the Cu(II) complex of cyclen was enhanced remarkably (111). Poly(chloromethylstyrene-co-divinylbenzene) (PCD) was prepared as a derivative of polystyrene in which all of the styryl residues contained chloromethyl groups. By the substitution of chloro groups of PCD with various nucleophiles, PCD derivative BA was prepared. y-Globulin was hydrolyzed upon incubation with BA, whose half-life was as short as 1 h at 25°C and pH 7 in the presence of excess BA. The rates for hydrolysis of y-globulin by the Cu(II) complex of cyclen itself dissolved in water were also measured. Comparison of rate data collected at the same catalyst concentrations revealed that the proteolytic activity of the Cu(II) complex of cyclen was... 

Chloromethylated cross-linked polystyrene was used to initiate the graft copolymerization of several 2-substituted-2-oxazoline derivatives (130, 131). Allylic chloride from 1-chloro-l,3-butadiene-butadiene copolymer and from poly(vinyl chloride) was used to initiate the graft copolymerization of 2-methyl-2-oxazoline (132. 133). 

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). 

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