BACKGROUND OF THE INVENTION AND PRIOR ART

Organic synthesis is of fundamental importance in the discovery of new pharmaceuticals, agrochemicals, and advanced materials. For example, during the discovery phase to develop a pharmaceutical, the synthesis of a large number of compounds is needed for biological evaluation and optimization. However, the labor-intensive nature of organic synthesis and its hazardous conditions have not changed fundamentally despite other significant advances. Typically, after reaction completion, a work-up or clean-up procedure is needed to quench the active intermediate (e.g. acid chloride) and catalyst(s) and remove water-soluble inorganic byproducts (e.g. salts) and polar solvents, which can detrimentally affect chromatographic separation or subsequent processing. The ultimate goal of work-up is to separate the organic and aqueous components present after reaction completion. Thus, reaction work-up is a particularly time- and labor-consuming practice. (Cork, D.; Hird, N.Drug Discov. Today2002, 7, 56-63.)

The most common prior reaction work-up procedure has at its heart liquid-liquid extraction (LLE) using a separatory funnel. The practice of LLE dates back to the late 19th century. It is based on the partition of an organic compound between two liquid phases (usually an organic and aqueous phase). Generally, the organic compound will preferentially dissolve in one phase versus the other, enabling separation and purification. A typical LLE-based work-up procedure has the following steps:

1) The crude reaction mixture is quenched with a suitable aqueous solution (e.g. saturated NH4Cl solution) to stop the reaction and destroy excess reagent(s)/intermediate(s)/catalyst(s) and to dissolve water-soluble by-products. The quenching process typically leaves a complex mixture of compounds that are partially soluble in both the organic and aqueous phases of the quenched reaction mixture.

2) LLE is performed to separate the organic compounds from the aqueous phase solution consisting of water and water-soluble compounds. The organic compounds are extracted from the quenched reaction mixture with suitable (chemistry-dependent) organic solvents (e.g., diethyl ether or ethyl acetate) in an iterative fashion. The combined organic layers with extracted organics are then washed with an aqueous solution to remove any residual inorganic by-products.

3) The organic phase is dried using a solid drying agent such as Na2SO4. Drying may take 10 minutes to several hours depending on the drying agent and solvent used. The drying agent is then removed by filtration and the solvents in the filtrate are evaporated under vacuum, leaving the organic reaction products behind as a residue.

4) The organic residue is further purified by flash chromatography or other processes.

All of these steps are labor- and time-consuming, especially for the work-up of a large number of reactions. Additional disadvantages of LLE include the use of relatively large volumes of solvent, possible emulsion formation that blurs the separation between liquid phases, and a relatively high chance of contact with potentially hazardous chemicals and solvents. (Cork, D.; Hird, N.Combinatorial chemistry2002, 7, 56.)

To overcome these drawbacks, the inventors developed a substantially faster technique for work-up that relied on a porous organic polymer (‘Porelite’) supported solvent phase (a ‘rigid solvent’) to extract organic products from an aqueous reaction mixture. Porelite was based on a then-new type of porous polymer—a High Internal Phase Emulsion polymer (‘polyHIPE’) containing extremely large and inter-connected pores. This improvement was disclosed in U.S. Pat. No. 9,272,260 to Gerald B. Hammond and Bo Xu. In U.S. Pat. No. 9,272,260, the porous organic solid support functioned like a honeycomb with an array of interior spaces to support or hold in place very small droplets of an organic extraction solvent through the ‘attraction’ (polarity-based) of the honeycomb (organic polymer) for the solvent or desired organic products. In this new invention, the molecules of the organic compounds (solvent or desired products) permeate into a solid polymer (as either a solid or coating on a support) into which the aqueous phase cannot permeate. Additionally with respect to U.S. Pat. No. 9,272,260, large scale preparation of a polyHIPE-type polymer such as Porelite is difficult. A large amount of a templating surfactant was used in the preparation of Porelite and the complete removal of the surfactant is also difficult. Also, the density of polystyrene foam-like Porelite is very low (ca. 0.15 gram/mL), which causes handling and weighing problems, particularly in low ambient humidity conditions that promote static electric charge generation. This new invention is an improvement in that the materials are more dense and are free-flowing powders or easy-to-handle sponges, foams or pieces of porous polymer solids. They are prepared by a simple coating operation or commercially available as foams or sponges made for other applications.

Typically, after reaction completion, a work-up or clean-up procedure is needed to quench the active intermediate (e.g. acid chloride) and catalyst(s) and remove water-soluble inorganic byproducts (e.g. salts) and polar solvents, which can affect chromatographic separation. Reaction work-up is a particularly time- and labor-consuming practice.

Therefore, it is highly desired to develop a faster reaction work-up protocol using an easy-to-handle absorbent which can be prepared using a scalable protocol.

SUMMARY OF INVENTION

The present invention discloses materials and methods for substantially reducing the time required for extracting organic compounds dissolved in an aqueous phase or aqueous solution, typically the major part of reaction work-up. The inventive material uses silicone elastomer-coated glass powders, magnetic powders and sponges, foams or other porous supports as absorbents to extract organic compounds from an aqueous mixture. After separation from the mixture, these different forms now loaded with organic compounds can serve as a convenient input for flash chromatographic separations or other processing steps. With these techniques, tedious liquid-liquid extractions are replaced by a simple solid filtration or transfer and emulsion formation is eliminated. These versatile sorbents can also be used for larger scale work-ups, various extractions of organics from an aqueous phase (e.g., water purification) or gas phase and various analytical or other applications. They are also easy to handle, overcoming the handling problems with the previously-developed Porelite.

