Solution-phase synthesis validation

The next phase for SP is the validation of the selected route in solution. It is useful to check the outcome of the reaction on several compounds to uncover potential weaknesses. This step is obviously redundant in the solution phase, because it corresponds to the following chemical assessment step, even though the synthesis of a few more fully characterized discretes may be desirable (Fig. 8.7, top). Typically, the assessment of the chemistry in solution takes several weeks to check a few representative monomers with different reactivities in order to discard unsuitable monomer... 

Ideal reactions for solution-phase parallel synthesis are those that are kinetically and thermodynamically favored, are tolerant of diverse functionality, and have a broad range of reactant tolerance. In this approach, capture resins and extraction procedures are often used for preliminary purification. The solution-phase reaction conditions must be validated in terms of scope and optimal reaction conditions over the range of reactants. Two common strategies for solution libraries involve derivatization of preformed functionalized scaffolds and multicomponent condensation reactions, for example, the Ugi reaction, the Passerini reaction, and the formation of hydroxyamininimides from an ester, a hydrazine, and an epoxide. 

As of today, apart from straightforward one-step derivatizations, the vast majority of analoging procedures by combinatorial synthesis are carried out on solid support. This overview focuses on organic chemistry adapted to the operation mode of solid-phase synthesis. The translation of protocols from solution chemistry to validated solid-phase procedures is a nontrivial task, often... 

Essentially all of the engineering thermodynamic correlations used in pollution control models and synthesis gas phase equilibria, chemical equilibria, and enthalpy calculation schemes have their foundations in fundamental theory. Experimental data, in addition to being directly useful to designers, allows the correlation developer to assess the validity and suitability of his model. Included within the third section (Properties of Aqueous Solutions—Theory, Experiment, and Prediction) are chapters providing both comprehensive reviews and detailed descriptions of specific areas of concern in the theory and properties of aqueous solutions. 

From the viewpoint of scientific methodology there are three main tasks in CAPE representation of the problem, generation of several alternative solutions, and selection of the best one. These tasks correspond to the activities realized in four phases of any scientific method analysis (description of the problem and identification of the objectives), hypothesis (generation of solutions), synthesis (comparing the solutions), and validation (formulation of conclusions). The activities realized in the last two phases correspond to the selection task in CAPE. 

Unfortunately, the simple picture shown in Fig. 1 is only valid for pure CO2 and the phase behavior of mixtures is much more compHcated [4]. It is not sufficient to adjust temperature and pressure above the critical values of pure CO2 to assure a single-phase reaction mixture in the presence of other components The phase behavior of mixtures is a function of composition and the actual phase diagram can vary considerably even for seemingly similar components. Reaction solutions are mixtures of at least three (substrate, product and solvent) but in most cases more components of variable composition and a full description of the phase behavior is not practical in most cases. Fortunately, most exploratory studies towards chemical synthesis are carried out under fairly dilute conditions (substrate concentrations < 10 mol %), and the problem can therefore often be simplified to getting an idea of the solubiUty of the various components in SCCO2. 

---