DMAP polymer

Figure 4. Direct amide formation by DMAP polymer via mixed anhydride fonnation.

Dimethylamino)pyridine (1, DMAP) and its analogs, particularly 4-(pyrrolidino)pyridine (2, PPY) have acquired enormous importance and utility as supemucleophilic catalysts in synthetic organic and polymer chemistry (1, 2). 

DMAP has been found to improve the coupling reaction in solid phase peptide synthesis (4). Polypeptides synthesized via the DMAP-DCC method were found to be of higher purity compared to other methods of synthesis. In polymer chemistry, DMAP has been used for hardening of resins and in the synthesis of polyurethanes, (5) polycarbonates, (6) and polyphenyleneoxides (7) ... 

The tremendous scope of utilization of DMAP and PPY as catalysts has led to an active interest in the development of their polymeric analogs. The pioneering work was carried out by Hierl et al (8) and Delaney et al. (9). They attached 4-dialkyl-aminopyridine derivatives to poly(ethyleneimine) and found the modified polymers to be highly active catalysts for hydrolysis of p-nitrophenylcarboxylates. Since then, many research groups have reported the synthesis of polymers functionalized with 4-dialkyl-aminopyridine (10-18). 

In order to determine the efficiency of the polymers as reagents in nucleophilic catalysis, it was decided to study the rate of quaternization with benzyl chloride. Table I shows the second-order-rate constants for the benzylation reaction in ethanol. Comparison with DMAP indicates that poly(butadiene-co-pyrrolidinopyridine) is the most reactive of all the polymers examined and is even more reactive than the monomeric model. This enhanced reactivity is probably due to the enhanced hydrophobicity of the polymer chain in the vicinity of the reactive sites. 

The desired polymer-bound tryptophan was rapidly generated under microwave irradiation, employing a classical esterification protocol using N,N -dicydohexylcar-bodiimide (DCC) and a catalytic amount of N,N-dimethylaminopyridine (DMAP), followed by subsequent Fmoc deprotection (Scheme 7.68). Cyclocondensations with various carbonyl compounds were performed with catalytic amounts of p-toluene-... 

Polymer-bound 1-hydroxybenzotriazole 1008 reacts with carboxylic acids in the presence of 1,3-diisopropylcarbo-diimide (1,3-DIC) and DMAP to produce esters 1009. Treated with hydroxylamine, esters 1009 are converted to hydroxamic acids 1010 (Scheme 167) <20030BC850>. Starting 1-hydroxybenzotriazole 1008 is recycled in the process and can be used for other syntheses. This method is well suited for automated synthesis of a library of hydroxamic acids. In similar applications of polymer-supported 1-hydroxybenzotriazole 1008, a wide variety of amides is synthesized <1997JOC2594, 2002JC0576>. 

All maleimides were synthesized according to standard procedures.16 Maleic anhydride, dimethyl maleate, and diethyl fiimarate were purchased from Aldrich Chemical Co. and used as received. 1,4-Cyclohexanedimethanol divinyl ether (CHVE) and tetraethylene glycol divinyl ether (CHVE) were used as received from International Speciality Products. Bis(4-vinyloxybutyl) isophthalate (IPDBVE) and bis(vinyloxybutyl)succinate (SEGDVE) were obtained from Allied-Signal and used without further purification. All acrylates were used as received from either Aldrich Chemical Co. or Scientific Polymer Products. 2,2-Dimethoxy-2-phenylacetophenone (DMAP) was used as received from Ciba Specialty Chemicals. 

A related series of 5-substituted-2-amino-oxadiazole compounds have also been prepared in a one-pot procedure using a microwave-assisted cyclisation procedure (Scheme 6.26)164. Rapid preparation of the pre-requisite ureas from the mono acyl hydrazines and various isocyanates (or the isothiocyanate) was easily achieved by simple mixing. The resulting products were then cyclo dehydrated by one of the two procedures either by the addition of polymer-supported DMAP and tosyl chloride or alternatively with an immobilised carbodiimide and catalytic sulphonic acid. Purity in most cases was excellent after only filtration through a small plug of silica but an SCX-2 cartridge (sulphonic acid functionalised - catch and release) could be used in the cases where reactions required additional purification. 

EtN=C=N(CH2)3NMe2HCl, DMAP EtN=C=N(CH2)3iWe2-polymer EtN=C=N(CH2)3NMe2, HOBt, (base)... 

The ability of the boron atom of 59 to engage in a donor-acceptor interaction was illustrated with DMAP and DABCO (DABCO = diazabi-cyclo-[2.2.2]-octane) that readily formed the corresponding Lewis adducts. Interestingly, a similar behavior was retained after coordination of the phosphorus atom to palladium. The formation of the Lewis base adducts 66a and 66b of complex 65 (Scheme 38) was supported by solid-state 31P and nB CP/MAS-NMR spectroscopy (<5 1 B = 5-6 ppm), although the occurrence of decomposition and/or dissociation processes impeded spectroscopic characterization in solution and recrystallization to obtain X-ray quality crystals. Compounds 66a and 66b substantiate the ability of ambiphilic compounds to engage concomitantly into the coordination of donor and acceptor moieties. Such a dual behavior opens interesting perspectives for the preparation of metallo-polymers and multimetallic complexes. 

Functionalisation with bulky hydrophobic carboxylic acids/DCC was studied for the synthesis of amphiphilic polymers based on dextran. Bile acid is covalently bound to dextran (Fig. 27) through ester linkage in the presence of DCC/DMAP (added in dichloromethane) as coupling reagent. 

The 17 membered ring lactone is also obtained in 96 % yield, while shorter chains produce lower yields. Under similar conditions without DMAP hydrochloride, mixtures of the lactones and linear polymers are obtained. ... 

Cross-linking of 23b by ethylene dimethacrylate (EDMA) leads to formation of porous monolithic sulfobetaine polymers [258]. Alternatively, grafting of the internal surfaces of porous poly(trimethylpropane trimethacrylate) (polyTRIM) by DMAPS provides grafted monoliths. Both synthesis routes yielded polymers capable of interacting reversibly with proteins in aqueous solutions. The SEM pictures show the copolymerized monolith poly(DMAPS-co-EDMA) comprised of spherical units with average diameter approximately... 

Racemization occurring during esterification of protected amino acids to hydroxymethyl polymers is a well-recognized problem.PP l This reaction is promoted by the use of DMAP as catalyst,P l and racemization is particularly pronounced in the case of cysteine.P By the use of optimized esterification methods racemization can be reduced, but not totally sup-pressed.P l When starting with halomethyl-functionalized resins, such as 2-chlorotrityl chloride resin,P l bromo-SASRIN resin,P l or 4-(bromomethyl)phenoxyacetamide res-in,P l racemization levels are significantly lowered. Alternatively, racemization is largely prevented by using the TDO esters without DMAP,f P°l or PyAOP in the presence of DIPEA at low temperature.P l... 

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