Structure automated parallel

Automated parallel experiments were carried out to rapidly screen and optimize the reaction conditions for ATRP of methyl methacrylate (MMA) [34]. A set of 108 different reactions was designed for this purpose. Different initiators and different metal salts have been used, namely ethyl-2-bromo-tTo-butyrate (EBIB), methyl bromo propionate (MBP), (1-bromo ethyl) benzene (BEB), and p-toluene sulfonyl chloride (TsCl), and CuBr, CuCl, CuSCN, FeBr2, and FeCl2, respectively. 2,2 -Bipyridine and its derivatives were used as ligands. The overall reaction scheme and the structure of the used reagents are shown in Scheme 2. 

A reactor block consisting of 16 reactors was divided into 4 zones with 4 different CTA to initiator ratios, and 4 different acrylates or methacrylates were used in each set of experiments. The polymerization of tert-buiyl methacrylate was repeated four times to demonstrate the reproducibility of the polymerization in an automated parallel synthesizer. Structural analysis of the polymers revealed that there was less than 10% deviation in the number average molar mass (Mn) and the PDI values. 

H. Tanaka, N. Matoba, H. Tsukamoto, H. Takimoto, H. Yamada, and T. Takahashi, Automated parallel synthesis of a protected oligosaccharide library based upon the structure of dimeric Lewis X by one-pot sequential glycosylation, SYNLETT, (2005) 824—828. 

We have developed an automated parallel synthesis methodology that permits the rapid and detailed Investigation of hydrothermal systems. The general procedure is as follows automatic dispensing of reagents into autoclave blocks followed by synthesis, product isolation and automated structure analysis with X-ray diffractometry. Here we describe the application of this technique to the exploration of the aluminophosphate synthesis field. The effects of template, template concentration, A1 sources as well as mixed template systems are investigated. Emphasis is put on the study of cooperative structure direction effects. 

To understand the effect of molecular structure on the thermoresponsive OEGMA (co) polymers, polymer libraries were evaluated. By systematically varying the structure, for example, length or composition, of the copolymers followed by evaluation of the thermoresponsive properties, structure-property relationships are revealed. However, the preparation of such libraries of polymers can be very time consuming and is prone to human errors due to less-challenging repetition of similar experiments. Therefore, we have adapted the use of automated parallel synthesis robots for both the optimization of polymerization conditions as well as the preparation of polymer libraries (Hoogenboom et al, 2003 Meier et al, 2004). These synthesis robots will be discussed in this section as well as their use for the optimization of the RAFT polymerization process to demonstrate the added value of such equipment. 

Figure 22.9 Left Schematic representation of the main reactions in the RAFT polymerization process. The background shows a picture of the automated parallel RAFT polymerizations. Right Chemical structure of the used 2-cyano-2-butyl dithiobenzoate (CBDB) RAFT agent and azibisisobutyronitrile (AIBN) initiator.

Parallel processing of synthetic operations has been one of the cornerstones of medicinal and high-throughput synthesis for years. In the parallel synthesis of compound libraries, compounds are synthesized using ordered arrays of spatially separated reaction vessels adhering to the traditional one vessel/one compound philosophy. The defined location of the compound in the array provides the structure of the compound. A commonly used format for parallel synthesis is the 96-well microtiter plate, and today combinatorial libraries comprising hundreds to thousands of compounds can be synthesized by parallel synthesis, often in an automated fashion. 

A one pot formation and purification of a 5-arylidine 4-thiazolidinone library has also been reported using polymer scavenging as the principle method of purification. An automated synthesizer was employed to make a parallel array of 4080 4-thiazolidinones, prepared simultaneously from a 3-component condensation of mercaptoacetic acid with an amine and a carbonyl compound. Further structural decoration was then introduced using the libraries from libraries principle where the core template was derivatized via an aldol reaction with a second carbonyl unit at the 5-methylene position (Scheme 2.57) [84]. After both synthetic steps. 

To carry out this parallel combinatorial approach towards the evaluation of organic reactions the automated analysis and structure elucidation of a large number... 

Solid-phase synthesis techniques applied either in a parallel fashion in automated synthesis or in split-pool-synthesis enable the rapid production of compound libraries containing thousands of members. But the original expectation that new hits will be discovered solely by the creation of a large quantity of library members was not fulfilled. Some of the libraries contained hardly any hit, because the underlying structures therein were not biologically relevant. Thus an old question returned Where in the almost indefinite space of thinkable chemical compounds are the structures which are of biological relevance [2] ... 

The word library is used to define a collection of compounds usually built around a common structural motif. There are three general approaches to library preparation parallel synthesis, mixture synthesis and split synthesis. One of these preferred strategies, parallel synthesis, is the approach where the compounds are made individually by automated or semi-automated methods. The library members may be made either in solution by classical methods, in solution attached to a polymeric carrier or on solid support. In parallel synthesis there must be linkage to a spatially defined position. The structure of the product is inferred from the position of the reactor and by the order of addition of the synthons and reagents at that position in space. Every possible member, resulting from the combinatorial mix of the synthons, need not be included in the library. 

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