Catalyst Library Preparation

This mapping gives a smooth variation in composition across the array, as illustrated in the eolor map made from cyan, magenta, yellow, and blaek inks. According to the eombinatorial theory, for a combinatorial map of n different components, the number of the total combinations N is given by Equation 12.4  

This preparation method of catalyst array has an advantage, which is that the high surface-area catalysts can be screened under similar circumstances as are used in the traditional half-cell electrochemical testing. An additional advantage is that through this approach, the effect of other chemical/physical variables besides composition can also be studied, for example, variables such as Pt loading and catalyst particle size, as has been done in Guerin s work. 

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Figure 3.21 Ternary catalyst library prepared by wet impregnation of oxidized aluminum carriers with Pd, Co and Cu salts [51]...

Table 11.2 Catalyst libraries prepared by irTtpregnation techniques. 

Figure 12.9. Schematic drawing of an assembled electrochemical cell for combinatorial screening catalyst libraries prepared by sputter deposition [22], (Reprinted from Joiunal of Power Sources, 163(1), Cooper JS, McGinn PJ. Combinatorial screening of thin film electrocatalysts for a direct methanol fuel cell anode, 330-8, 32006, with permission from Elsevier.)...

It is worth noting that combinatorial chemistry has only been explored in the field of fuel cell electrocatalysis for a short time (around ten years). Therefore, it is still a developing and maturing technology. With improvement in both catalyst library preparation and screening techniques, combinatorial methods will become more important in new fuel cell electrocatalyst development. It is also believed that this combinatorial method will speed up new catalyst exploration, and thus accelerate developments toward PEM fuel cell breakthrough and commercialization. 

A given ligand system was first prepared on the solid support, and a small collection of catalysts (library 1) generated by adding 11 different metals and in one case no metal (Scheme 23).119 It turned out that the best ee-value (19%) was in fact obtained in the metal-free system. Based on this... 

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... 

Particularly noteworthy examples are Entries 8 and 9 in Table 3.19 these represent a diastereoselective RCM in which the stereoselectivity is controlled by the catalyst [886]. Entries 17, 23 and 24 (Table 3.19) illustrate the use of RCM for the solid-phase synthesis of lactams [894]. RCM induces both ring closure to the lactam and cleavage from the support. Although elegant at first glance, the usefulness of this methodology will be limited if the products must be used without further purification (as is usually the case for compound libraries prepared by parallel synthesis). Because relatively large amounts of catalyst are required, the crude products will only be acceptable for assays in which transition metal complexes do not interfere. 

In the 1970s and 1980s, however, it was believed that the key to wider use of solid-phase supported reagents and catalysts is their adoption in industry for fine chemical and pharmaceutical manufacturing on a large scale. In fact, this restricted view hampered their wide use [7]. The dramatic developments in the need for compound library preparation in pharmaceutical and agrochemical industries have finally removed functionalized supports from their academic corner and helped reinvent them for industrial purposes and applications. 

A similar approach was reported by Lygo and co-workers who applied comparable anthracenylmethyl-based ammonium salts of type 26 in combination with 50% aqueous potassium hydroxide as a basic system at room temperature [26, 27a], Under these conditions the required O-alkylation at the alkaloid catalyst s hydroxyl group occurs in situ. The enantioselective alkylation reactions proceeded with somewhat lower enantioselectivity (up to 91% ee) compared with the results obtained with the Corey catalyst 25. The overall yields of esters of type 27 (obtained after imine hydrolysis) were in the range 40 to 86% [26]. A selected example is shown in Scheme 3.7. Because the pseudo-enantiomeric catalyst pairs 25 and 26 led to opposite enantiomers with comparable enantioselectivity, this procedure enables convenient access to both enantiomers. Recently, the Lygo group reported an in situ-preparation of the alkaloid-based phase transfer catalyst [27b] as well as the application of a new, highly effective phase-transfer catalyst derived from a-methyl-naphthylamine, which was found by screening of a catalyst library [27c],... 

The DMAP derivative 19a was tested for kinetic resolution of a variety of mono esters of cyclic cis diols (rac-20a-i) (Scheme 12.5) [15]. Catalyst 19a afforded selectivity factors up to 12.3 and highly enantioenriched mono esters 20 with conversions of 65-73%. For this type of reaction the selectivity of the Campbell catalyst 19b was similar (selectivity factor 13.2, Scheme 12.5) [16a], The latter catalyst was identified by screening of a 31-mer library prepared from the parent N-(4-pyridyl)-a-methylproline and a variety of amines [16a], The solid-phase-bound forms of N-(4-pyridyl)-a-methylproline, as reported by Anson et al. [16b], are easily recyclable acylation catalysts affording selectivity factors up to 11.9 in the kinetic resolution of the secondary alcohol rac-20b (Scheme 12.5). In the kinetic resolution of N-acylated amino alcohols, selectivity factors up to 21 were achieved by use of the Kawabata-Fuji catalyst 19a, and up to 18.8 by use of the Campbell system 19b (Scheme 12.5) [15, 16a]. 

Taylor and Morken extended the use of IR-thermography to the monitoring of the change in the heat of reaction on and in the surroundings of a bead carrying an active catalyst (Figure 5.4.4) [13]. In a search for acylation catalysts an encoded library of 3150 different potential nucleophilic catalysts was prepared by the split-and-mix procedure and tested for their acylation properties. The library beads were spread in a reaction solution of chloroform-ethanol-triethylamine-acetic anhydride, 40 6 6 3, and monitored with an IR camera. Whereas no detectable thermal... 

Holzwarth et al. (51) reported the synthesis and IR thermographic-imaging screening of a 37-member, focused discrete heterogeneous catalyst library L6 for oxidations and reductions. The library was prepared using sol-gel solution synthetic protocols (47, 51) to produce the library individuals as amorphous microporous mixed oxides (AMMs), which have previously shown heterogeneous catalytic properties (54, 55). The scaffolding metal oxides contained either Ti (subset 1, Fig. 11.7) or Si (subset 2), and many active metal components were used. The complete structure of L6 is reported... 

Monger et al. (100) reported the synthesis and screening of a 1344-member discrete polymer library L15 as a source of catalysts for the dehydration of the p-hydroxy ketone 11.33 to the enone 11.34 (equation 1, Fig. 11.21). The main feamres of L15, obtained from poly(acrylic anhydride) 11.32 (101) as a scaffold and the amine monomer set Mi (11 representatives) are reported in Fig. 11.21. The protocols for library preparation followed the same principles seen for L14 in the previous section. The presence of both acidic (the COOH backbone, to protonate the OH in 11.33 and promote its departure) and basic groups (side chains in some Mi representatives, to promote proton abstraction) should fulfill the core functional requirements to exert the overall catalytic activity. 

For 4 cyclen-containing carboxylic acids, 18 amines, 17 aldehydes, and 5 isocyanides were used to build the library. For 3 cyclen-containing amines, 18 carboxylic acids, 17 aldehydes, and 5 isocyanides were utilized to construct the library. In total, therefore, 7500 combinations of the four components were employed for the Ugi reaction. As each Ugi condensation reaction produces a stereogenic carbon atom, the total number of catalyst candidates prepared in this study was 15,000. The number of compounds to be placed in one reaction vessel was adjusted to produce 9 different combinations and, consequently, 18 catalyst candidates in each vessel. 

A key to widespread use of fuel cells as a power source is high-performance, low-cost manufacturable electrocatalyst. Ink-jet technology has been used in library preparation for methanol fuel cell catalysts discovery at Penn State University and Illinois Institute of Technology [34]. 

Catalyst library Catalyzed reaction Preparation details References... 

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