Quick Screen Solvents

Frank et aL reported examples of quickly screening solvents for organic solids. In one particular example, solubilities of aspirin in four different solvents (acetone, ethanol, chloroform, and cyclohexane) were used to regress the Hansen solubility parameters for the solute, aspirin. Once the Hansen solubility parameters are identified for aspirin, Frank et al. showed that one could quickly estimate the solubilities of aspirin in any solvent or solvent mixture as long as the Hansen solubility parameters are also available for the solvents. 

Frank TC, DowneyJR, and Gupta SK. Quickly Screen Solvents for Organic Solids. Chem Eng Progress 1999 95 41-61. 

Recently, Frank et al. (1999) presented a good review of these and other calculation-based methods to quickly screen solvents for use in organic solids crystallization processes. 

A simple way of applying enzymes in a non-aqueous reaction is through addition of lyophilized enzyme powder. With a hydrophobic solvent, this will create an enzyme suspension and, if other conditions (substrate, temperature, etc.) are acceptable, it will probably work. For a quick screening of a range of enzymes it may even be the most optimal setup. It is, however, well known that many enzymes lose activity upon lyophilization (which to some degree can be prevented by the use of lyoprotectants). Another concern is that enzyme dust is potentially allergenic if inhaled. 

A simple experimanc in which a proposed solvent is mixed with the feed mixture can be used to guide solvent selection evan if the equilibrium phases are not analyzed to determine concentrations. If lahotmory facilities are available, batch shakeout rests are often the mosi attractive way lo screen solvents and quickly identity a fow suitable candidates for further study. 

Since there are several options for solvent selection tools, there will be tradeoffs between completeness and the time and information necessary to make a decision. Table 15.2 presents the examples of tools from simple to more sophisticated approaches. One can perform a quick screen using few data points, but after the initial screening, one may need to do some advanced computer modeling before the experimental validation. 

Note 2—quick screening can be conducted by injecting the solvent and sample once or twice and comparing relative area counts. 

The selection of a mobile diase for the separation of simple aixtures may not be a particuleurly difficult problem and can be arrived at quite quickly by trial and error. Solvent systems can be screened in parallel using either several development chambers or a device like the Camag Vario KS chamber, which allows the simultaneous evaluation of a number of solvents by allowing each of these to migrate along parallel channels scored on a single TLC plate [8]. However, whenever the number of components in a mixture exceeds all but a small fraction of the spot capacity for the TLC system, a more systematic method of solvent optimization is required. 

Use of the above conditions in conjunction with the enol tosylate 32, provided only low yields of 22, prompting an extensive screening of structurally diverse phosphine ligands/solvents and palladium sources to attempt to define suitable conditions. Quite quickly a number of conditions were found to be effective, with chelating diphosphines being superior to monodentate phosphines (Table 9.7). In... 

Fluid from solid-phase extraction of wool was placed on simple screen-printed electrodes (an outer membrane was applied with an airbrush) [45]. The solvent was allowed to evaporate and, after an overnight incubation, the activity of the electrodes was measured quickly with reference to that of unexposed electrodes. It was possible to detect the presence of organo-phosphates which had been used to contaminate samples of untreated sheep wool (Fig. 28.3) (see Procedure 41 in CD accompanying this book). 

Flash Chromatography. In 1978, Still, Kahn, and Mitra75 published a quick-and-dirty prep method that has become very popular and even has its own name—flash chromatography. They used short, fat columns (1-5 cm i.d. x 18 in.), 40-65 xm silica, and low viscosity solvents (e.g., ethyl acetate/petroleum ether mixtures). The exact solvent mixture is selected by screening the sample via TLC to give an R value of about 0.35. However, they found that when the proportion of the polar component was small, it was better to use about half as much of it for the column separation as was used for TLC. 

Muzart s group has recently described the use of molybdenum catalysts with the hydrogen peroxide adduct, sodium percarbonate and a phase-transfer agent.198 The molybdenum catalyst used in the study was Mo02(acac)2, and the solvents screened were dichloroethane and acetonitrile. The active species is a Mo peroxo complex and in common with other methods based on Mo and W catalysts, secondary, allylic and benzylic alcohols react quickly, and give higher yields of carbonyl product than primary aliphatic alcohols. 

In the first instance, it is used to confirm a diagnosis when dealing with a patient with a metabolic problem. When the routine chemical screens indicate the presence of abnormal metabolites or raised levels of the usual metabolites, then MS can positively confirm their identity and thus a diagnosis, or, should it be a new inborn error, point to the metabolic pathways which are affected. In many of the organic acidurias described, the defect leads to gross excretion of one or more compounds and, as quantitative extraction is not necessary for their detection, simple solvent or other methods are normally used. In some instances it is vital that analysis be carried out quickly so as to indicate the most suitable clinical management of an acutely ill patient. 

An ingeniously simple screening method was used by Britain and Gemeinhardt [146] to evaluate catalysts for the isocyanate/hydroxyl reaction. To approximate as closely as possible actual polymerization conditions, the 80 20 ratio of 2,4- and 2,6-tolylene diisocyanate (80 20 TDI) isomers and a polyether triol of 3000 molecular weight were mixed at NCO OH ratio of 1.0. A 10% solution of catalyst in dry dioxane was added, the final catalyst concentration being 1% of the weight of polyether. The time for the mixture to gel at 70°C was noted as an indication of catalytic strength. This technique used the same reactants employed in one-shot flexible polyether-based foam systems, almost completely eliminated solvent, and was used to screen quickly hundreds of possible catalysts. 

With the development of the potentiometric technique as describe above, paH determinations can now be made very quickly and easily. This makes the screening of any buffer system in any mixed solvent much easier. Data concerning the paH of three buffer systems (cacodylate, phosphate, Tris) in three mixed solvents of water with ethylene glycol, methanol, glycerol at different volume ratios between +20° and their freezing points are summarized in Tables XXIII—... 

In this single-solvent polymorph screening approach, the solvent is added to the API and heated to an appropriate temperature until the solid is completely dissolved. The resulting solution is quickly cooled to a specific crystallization temperature chosen to create the desired degree of supersaturation. Rapid cooling... 

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