Silica-based scavengers

The silica-based scavenger has much faster kinetics which allows it to scavenge HOBt in only five minutes (Table 3.1). 

Comparable results were achieved with the silica-based diamine (3.0 equivalents of the amine functionality). At room temperature, the excess anhydride was scavenged within 4 h. On the other hand, microwave heating at 100 °C in a sealed ves-... 

Fig. 7.10 Polymer-supported scavengers polystyrene-bound diamine (top left), silica-based diamine (top right), Stratosphere Plugs (bottom left), and Synphase Lanterns (bottom right).

Removing residual transition metals after reaction completion is a major task for many chemists in the pharmaceutical industry. The toxic nature of transition metals means their concentration has to be reduced to the single digit ppm level for the material to be used in vivo and in clinical work. Silicycle Inc. is a silica gel company who has commercialized several functionalized silica based metal scavengers for the purification of active pharmaceutical ingredients. Scheme 9.1 shows the process for using silica based metal scavengers. 

Silicycle offers a wide range of silica-based metal scavenger products (Figure 9.1 ) to simplify the purification step and remove various transition metals. These metal scavengers are based on functionalized silica designed to react and bind excess... 

Several specialized silica-based functionalized platinum scavengers such as N-acetyl-L-cysteine, 2-aminoethyl sulfide, 2-mercaptoethyl ethyl sulfide, 3-mercapto-propyl ethyl sulfide, pentaerythritol 2-mercaptoacetate ethyl sulfide and triamine ethyl sulfide amide, developed by Strem Chemicals, are also available. These scavengers are highly stable and available in pure forms, which successfully scavenge platinum metal ions in batch processes. 

Silica-based metal scavengers, such as pentaerythritol 2-mercaptoacetate ethyl sulfide and 3-mercaptopropyl ethyl sulfide, which have been developed by Phos-phonics are used to remove rhodium and iron across all oxidation states. These scavengers work well in virtually all solvents, including water, and are available in various particle sizes. 

The most popular reversed-phase columns today are manufactured from silica-based bonded phases, and among those the Cjg-type bonded phase is most frequently used. As we have seen in Section 6.2, these bonded phases are prepared by reacting silica with a reactive silane that carries the ligand after which the phase is named. Commonly, chlorosilanes are used as the reactive silane in the presence of a scavenger of the hydrochloric acid, which is a byproduct of this reaction ... 

To verify whether the Pd(OH)2/C system was truly heterogeneous or not, a series of three-phase tests were carried out (Scheme 14.2). In the first case, the aryl halide was anchored to a Wang resin via an amide linker. Under standard conditions for 4.5 h, 100% conversion of supported substrate to arylated product was observed. In addition, in the presence of a silica-supported thiol-based scavenger resin (thiols are known to have a very high affinity for palladium), less than 5% of the desired product formed. These results led to the determination of... 

NH2 is readily oxidized, so peroxides (in diethyl ether, dioxane or tetrahydrofuran) should be strictly avoided. Ketones and aldehydes react to give Schiff bases." Amino silicas are less stable towards hydrolysis than other bonded phases and it is recommended to use a pre-column (scavenger column) to saturate the mobile phase. 

Although many groups now use MnO-vermiculite or silica gel as an oxygen scavenger, we find that the standard commercially available BASF catalyst works satisfactorily for our research and can be regenerated at substantially lower temperatures than the manganese based material (see ref. 1 pp. 74-80). 

There are several players in this field who have developed silica and polymer based functionalized metal scavengers - SiliCycle, Polymer Labs, Reaxa and Aldrich are key players in the medicinal and process chemistry fields. ChemRoutes Corporation has carried out significant research effort in this field, commercialized by the above-mentioned players, and is now developing novel technologies in the metal scavenging area for the nanotechnology field. Examples of the chemistries commercialized by the various players are given below. 

In addition to the silica or polymer based resins mentioned above, polymer based resins with specific chemistries at the functional group have also been widely used as palladium scavengers for synthetic organic reactions. These include macroporous polystyrene-bound trimercaptotriazine (TMT). It, along with the thiol resin, has been found to be highly effective in reducing the concentration of palladium in both aqueous and non-aqueous solutions [18]. 

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