Mixture synthesis

As a chemical compound, methane is not very reactive. It does not react with acids or bases under normal conditions. It reacts, however, with a limited number of reagents such as oxygen and chlorine under specific conditions. For example, it is partially oxidized with a limited amount of oxygen to a carbon monoxide-hydrogen mixture at high temperatures in presence of a catalyst. The mixture (synthesis gas) is an important building block for many chemicals. (Chapter 5). 

As mentioned in Chapter 2, methane is a one-carhon paraffinic hydrocarbon that is not very reactive under normal conditions. Only a few chemicals can he produced directly from methane under relatively severe conditions. Chlorination of methane is only possible by thermal or photochemical initiation. Methane can be partially oxidized with a limited amount of oxygen or in presence of steam to a synthesis gas mixture. Many chemicals can be produced from methane via the more reactive synthesis gas mixture. Synthesis gas is the precursor for two major chemicals, ammonia and methanol. Both compounds are the hosts for many important petrochemical products. Figure 5-1 shows the important chemicals based on methane, synthesis gas, methanol, and ammonia. ... 

Fluorous Mixture Synthesis of Fused-Tricyclic Hydantoins. 114... 

Fig. 32 Fluorous mixture synthesis of fused-tricyclic hydantoins. Reagents and conditions a Mo(CO)6, DMSO, toluene, MW 150 °C, 35 min, closed system b TFA CH2CI2 (1 1), rt c PhC2H4NH2, PyBOP, i-Pr2EtN, MeOH, CH2CI2 followed by flash chromatography and F-HPLC d i-Pr2EtN, MeOH, MW 140 °C, 40 min, followed by F-SPE...

The application of fluorous mixture synthesis (FMS) for deriving natural products and their stereoisomers was demonstrated by the total synthesis of all 16 stereoisomers of the pine sawfly sex pheromoned ... 

The reforming step makes a hydrogen-carbon monoxide mixture (synthesis gas) that is used to produce a variety of other chemicals. 

Much of the early work in combinatorial chemistry focused on the preparation of large mixtures of compounds. The most widely used technique for mixture synthesis is the split/recombine method which assures that each component of the mixture is present in approximately equimolar concentrations. The structures of the bound ligands are determined either through an iterative, or reclusive, deconvolution strategy or through the use of encoded libraries. 

The chapter by Kiely reviews the preparation of libraries as mixtures from 1995 to the present. The important areas which are reviewed are methods of preparation, means of identifying active compounds from the mixtures, and why one might wish to prepare mixtures. The chapter also includes the preparation of mixtures of non-peptide molecules, as well as peptidomimetic molecules, and even a few examples of peptides. Examples are presented where mixture synthesis and screening have been effective in identifying interesting biological leads. 

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. 

In contrast, combinatorial libraries represent a subclassification and define a library in which every possible member that can be generated from the sets of reactants is present. Such libraries can be prepared by parallel synthesis, but are much more commonly synthesized by either mixture synthesis or split synthesis. Because of a commonality in structure among the members in each set of reactants and the optimized reaction conditions used, combinatorial libraries are composed of variants around a scaffold where the substituents control much of the diversity. 

In this subsection we describe heat pumps, multieffect distillation of binary mixtures, synthesis of multicomponent distillation systems with heat integration, and multieffect distillation for thermally coupled configurations. 

Figure 1 Representative scheme for fluorous mixture synthesis...

Z. Luo, Q. Zhang, Y. Oderaotoshi, and D. P. Curran, Fluorous mixture synthesis A fluorous-tagging strategy for the synthesis and separation of mixtures of organic compounds, Science, 291 (2001), 1766-1769. 

W. Zhang, Y. Lu, C. H.-T. Chen, L. Zeng, and D. B. Kassel, Fluorous Mixture Synthesis of Two Libraries with Hydrantoin-, and Benzodiazepinedione-Fused Heterocyclic Scaffolds, / Comb. Chem. 8 (2006), 687-695. 

Process options for the production of homochiral compounds are summarized in Fig. 2. The three basic routes are separation of racemic mixture, synthesis using a naturally occurring chiral synthon, and asymmetric synthesis using a prochiral intermediate. Historically, the efficiency of asymmetric synthesis has been capricious in terms of chemical and optical yield. Hence, from a practical, commercial process perspective, resolution via diastereomer crystallization has remained important for many commercial scale processes, for example, diltiazem. 

Fluorous Mixture Synthesis (FMS) of Drug-like Molecules and Enantiomers, Stereoisomers, and Analogues of Natural Products... 

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