Polymeric libraries

Nonoligomeric libraries. Peptide and peptoid libraries are examples of oligomeric (polymeric) libraries made up of repeating monomers (a-amino acids, A-substitutcd glycines). Random libraries composed of nonoligomeric compounds have been extensively explored. One illustration comes from the former laboratories at Organon (Fig. 1.6) (16). Thirteen different secondary amino-phenol inputs were attached to solid support by reaction with REM resin yielding resin-bound b-amino propionates. Two-site derivatization was then used to drive library diversity. The free phenolic OH was subjected to O-alkylation,... 

Menger et al. (33) also reported a similar polymeric library to identify catalysts for the hydrolysis of a phosphate ester (102), where a 30,000-fold increase versus the uncatalyzed reaction rate was obtained. Miller and Ford (103) reported the synthesis of a 32-member discrete polymer library based on anion-exchange latexes and its screening for the alkaline hydrolysis of p-nitrophenylalkane carboxylates. The reported efforts may represent just the tip of an iceberg in terms of opportunities granted by polymeric catalysts, and an expansion of knowledge derived from further efforts is to be expected in the near future. 

Systematic Polymeric Libraries via Atom Transfer Radical Polymerization... 

It is concluded that MALDI-ToFMS is a suitable method for direct analysis of low-MW additives in complex polymeric materials (in dissolution), in particular as a rapid screening technique (within 0.5 h). However, in order to turn this method into a general tool for identification and quantitation, considerably more work needs to be done. Identification of additives in polymeric matrices by means of MALDI-ToFMS would greatly benefit from reference libraries of additives contained in such matrices. This is not unlike the situation observed for ToF-SIMS. 

We have designed PBUILD, a new CHEMLAB module, for easy construction of random copolymers. A library of monomers has been developed from which the chemists can select a particular sequence to generate a polymeric model. PBUILD takes care of all the atom numbering, three dimensional coordinates, and knows about stereochemistry (tacticity) as well as positional isomerism (head to tail versus head to head attachment). The result is a model of the selected polymer (or more likely a polymer fragment) in an all trans conformation, inserted into the CHEMLAB molecular workspace in literally a few minutes. 

A solid-phase synthesis of pyrroloindolizines has been developed using this cycloaddition methodology, whereby an isoxazolopyrroloindolizine can be removed from the polymeric resin upon treatment with trifluoroacetic acid (TFA). This also results in ring opening of the isoxazole to give the isolated compound 210 (Scheme 58). A library of 96 such derivatives has been prepared in this way <1998TL5869>. 

Several combinatorial approaches to the discovery of transition metal based catalysts for olefin polymerization have been described. In one study Brookhart-type polymer-bound Ni- and Pd-(l,2-diimine) complexes were prepared and used in ethylene polymerization (Scheme 3).60,61 A resin-bound diketone was condensed with 48 commercially available aminoarenes having different steric properties. The library was then split into 48 nickel and 48 palladium complexes by reaction with [NiBr2(dme)] and [PdClMe(COD)], respectively, all 96 pre-catalysts being spatially addressable. 

Additionally, the authors chose 3-chloropropionyl chloride as the immobilized building block in order to carry out a ring-expansion approach, which led to the generation of a 14-member library of thioxotetrahydropyrimidinones [85, 86], The initially prepared polymer-bound chloropropionyl ester was efficiently transformed into the corresponding diamines by transamination utilizing several primary amines. These diamine intermediates could also be obtained by treatment of the pure polymeric support with acryloyl chloride and subsequent addition of the appropriate amines (Scheme 7.74). 

To date, the most frequently used ligand for combinatorial approaches to catalyst development have been imine-type ligands. From a synthetic point of view this is logical, since imines are readily accessible from the reaction of aldehydes with primary or secondary amines. Since there are large numbers of aldehydes and amines that are commercially available the synthesis of a variety of imine ligands with different electronic and steric properties is easily achieved. Additionally, catalysts based on imine ligands are useful in a number of different catalytic processes. Libraries of imine ligands have been used in catalysts of the Strecker reaction, the aza-Diels-Alder reaction, diethylzinc addition, epoxidation, carbene insertions, and alkene polymerizations. 

Figure 11.11 Library of amines and diketo compounds, which was employed in a polymerization catalyst study described in Section 11.7 [87], For simplicity, amines have a number and diketones a letter as library name.

We have discussed the structure and synthesis of the library of molecular catalysts for polymerization in Section 11.5.1. In the present section we want to take a closer look at the performance of the catalyst library and discuss the results obtained [87], The entire catalyst library was screened in a parallel autoclave bench with exchangeable autoclave cups and stirrers so as to remove the bottleneck of the entire workflow. Ethylene was the polymerizable monomer that was introduced as a gas, the molecular catalyst was dissolved in toluene and activated by methylalumoxane (MAO), the metal to MAO ratio was 5000. All reactions were carried out at 50°C at a total pressure of 10 bar. The activity of the catalysts was determined by measuring the gas uptake during the reaction and the weight of the obtained polymer. Figure 11.40 gives an overview of the catalytic performance of the entire library of catalysts prepared. It can clearly be seen that different metals display different activities. The following order can be observed for the activity of the different metals Fe(III) > Fe(II) > Cr(II) > Co(II) > Ni(II) > Cr(III). Apparently iron catalysts are far more active than any of the other central metal... 

A library of compounds prepared under homogeneous reaction conditions without the aid of polymeric supports... 

A synthesis of a library of benzoxazinones was also accomplished by blending several of the previously described methods (Scheme 2.42) [63]. This creative piece of work used a polymeric DMAP equivalent to mediate a coupling between aniline frag-... 

The use of polymeric materials for the rapid access of compound libraries in solution will be presented in chapter 5. 

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