Silica gels as solid supports

Furthermore, a versatile and efficient microwave-promoted combinatorial library synthesis of two long alkyl chain benzimidazoles from o-substituted amines and fatty adds employing either bentonite, alumina or silica gel as solid supports has been developed [33]. Bismuth chloride [34], montmoril-lonite clay K-10 [35] and silica impregnated with sulfuric acid [36] have also... 

Ogilvie KK, Nemer MN. Silica gel as solid-support in the synthesis of oligoribonucleotide. Tetrahedron Lett 21 4159-4162, 1980. 

The first of a series of papers from M. H. Caruthers group (367) at the University of Colorado appeared describing the potential of silica gel as a support for solid phase synthesis. 

A very interesting approach toward solid-supported synthesis under microwave heating was introduced by Chandrasekhar and coworkers [64], The authors developed a synthesis of N-alkyl imides on a solid phase under solvent-free conditions employing tantalum(V) chloride-doped silica gel as a Lewis acid catalyst (Scheme 7.53). 

Bis(indolyl)nitroethanes are obtained readily in 7-10 min in high yields (70-86%) on fine TLC-grade silica gel (5-40 pm) by Michael reaction of 3-(2 -nitrovinyl) indole with indoles. The same reaction reported requires 8-14 h for completion at room temperature [77]. Several functionalized resins have been prepared from Merrifield resin via a MW-assisted procedure that utilized mixed solvent system to facilitate the swelling of resins and coupling with microwaves [78], These resins can function as solid supports or polymeric scavengers in solid phase synthesis. 

In 2003, Balalaie and co-workers published a new paper in the area of imidazole synthesis39. In the above examples reported by Westman, ammonium acetate and primary amines act as the nitrogen source for the imidazole ring. In the Baladie novel one-pot three-component method, ammonium acetate was replaced by benzonitrile derivatives. Thus, benzil, primary amines and benzonitrile derivatives underwent a condensation reaction on acidic silica gel as the solid support, Scheme 5.23. The reaction mixtures were irradiated for 8 min in a domestic oven under solvent-free conditions to give the products in 58-92% yield. 

Eksborg and Schill1 separated a series of alkylamines on a cellulose column loaded with a 0.06 M aqueous picrate solution, of pH 11.2, using as mobile phase chloroform - 1-pentanol (19 1). Addition of the alcohol to the mobile phase was necessary to reduce tailing. Celite and porous silica gel were found to be less suitable as solid support for aqueous picrate solutions. At the low pH necessary to ionize tertiary, secondary and primary amines, picrate... 

A common method to prepare bonded-phase materials is to use silica gel as the solid support and to react functionalized organosilanes onto the surface hydroxyl groups of the silica gel. Of course, other solid support materials can be used provided that they present surface functional groups (e.g., OH, COOH, and NH2) that can participate in modification reactions. The flexibility offered by this approach leads to stationary phase materials with myriad functionalities. Fig. 3 illustrates commonly used organosilane reactants and two example reaction paths that lead to bonded-phase silica. For more discussion on bonded-phase materials, see Ref.. ... 

The process of ethane oxidative chlorination imposes heavy demands on the catalysts. The conventional salt supported catalysts are composed of Cu, K, Ca, Mn, Co, Fe, Mg, and other metal chlorides containing various additives these salts are precipitated on alumina, zeolites, silica gel, and other supports. Catalytic systems that represent solid solutions of iron cations in the lattice of the a-A Oa and a-Ct203 phases doped with cations, such as K, Ba, Ce, and Ag are also known [7]. 

In another study, supported catalysts are prepared with rhodium metal deposited on silica gel or alumina as solid support and modified with Diop. For further modification of these catalysts. (PhCN)2PiCl2 or Fe(CO)5 is used89. 

Since an overall interpretation of the precise role of silica gel, as well as zeolites and aluminosilicates in general, as surface catalysts has yet to be reached, further investigation is needed to understand the detailed reaction mechanisms taking place on the solid supports. 

Zou et al. have described an MSPD procedure for the extraction of eight sulfonamides from honey samples using C18 as solid support. After the MSPD, the sulfonamides were derivatized with 9-lluorenylmethylchloroformate (EMOC-Cl). The derivatives required further purification by silica gel SPE, prior to LC-UV determination. Average recoveries for most sulfonamides were >70%. Other polar sorbents, such as silica gel, CN- or NH2-bonded silica resulted in a strong absorption of the polar sulfonamides, providing very low recoveries. 

Flash chromatography is widely employed for the purification of crude products obtained by synthesis at a research laboratory scale (several grams) or isolated as extracts from natural products or fermentations. The solid support is based on silica gel, and the mobile phase is usually a mixture of a hydrocarbon, such as hexane or heptane, with an organic modifier, e.g. ethyl acetate, driven by low pressure air. (Recently the comparison of flash chromatography with countercurrent chromatography (CCC), a technique particularly adapted to preparative purposes, has been studied for the separation of nonchiral compounds [90].)... 

The synthesis of imidazoles is another reaction where the assistance of microwaves has been intensely investigated. Apart from the first synthesis described since 1995 [40-42], recently a combinatorial synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles has been described on inorganic solid support imder solvent-free conditions [43]. Different aldehydes and 1,2 dicarbonyl compounds 42 (mainly benzil and analogues) were reacted in the presence of ammonium acetate to give the trisubstituted ring 43. When a primary amine was added to the mixture, the tetrasubstituted imidazoles were obtained (Scheme 13). The reaction was done by adsorption of the reagent on a solid support, such as silica gel, alumina, montmorillonite KIO, bentonite or alumina followed by microwave irradiation for 20 min in an open vial (multimode reactor). The authors observed that when a non-acid support was used, addition of acetic acid was necessary to obtain good yields of the products. 

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