Functionalization covalent derivatization

As mentioned above, fhe second PASP strategy for purifying a crude reaction mixture after a synfhesis is to separate fhe desired product by selective covalent derivatization with a functionalized resin followed by filtration and rinsing. After fhe formation of the product in solution, it reacts selectively wifh a solid support while impurities and unreacted substrate remain in solution and are washed away. This resin-capture concept has been demonstrated in fhe context of fhe Ugi four-component condensation [51]. After the condensation, fhe reactivity of fhe enam-ide allowed fhe specific reaction with Wang resin under anhydrous acidic conditions. The resin was washed wifh methanol and dichloromefhane and fhe subsequent cleavage was performed with trifluoroacetic add in dichloromefhane. The final carboxyhc adds were characterized without further purification and were found to be > 95 % pure. 

In order to construct an ordered monolayer on a carbon surface, a premodified smooth and functionalized film is needed. Electrochemical reduction of diazonium salts or oxidation of amine-containing compounds and arylacetate produces free radicals, resulting in covalent derivatization of the carbon surface in nonaqueous solutions (Figure 3). The premodification by free radical grafting methods is quite mild, simple, and rapid experimentally. The monolayers prepared as a precursor film for subsequent assembly are stable to harsh environments and can endure elevated temperatures, and especially are organized in order, compact, and charge-rich. 

A powerful strategy to covalently derivatize carbon electrodes with monolayers and multilayers utilizes electrochemical reactions (75). Electron transfer is used to activate a heterogeneous chemical reaction. The adlayer is formed after generating the highly reactive species by oxidation or reduction of the solution-based molecule or a surface-based functional group. In most electrochemically assisted modification schemes, the reaction involves a carbon radical. 

Besides the preparation of glyconanotube conjugates by supramolecular interactions, another synthetic pathway commonly used involved covalent attachment of the saccharidic units on the CNT scaffolds. The progress recently recorded concerning the derivatization of unfunctionalized CNTs, allowing introduction of suitable anchoring functions at their surface, are the basis of this synthetic alternative.255... 

Aldehyde-containing macromolecules will react spontaneously with hydrazide compounds to form hydrazone linkages. The hydrazone bond is a form of Schiff base that is more stable than the Schiff base formed from the interaction of an aldehyde and an amine. The hydrazone, however, may be reduced and further stabilized by the same reductants utilized for reductive amination purposes (Chapter 3, Section 4.8). The addition of sodium cyanoborohydride to a hydrazide-aldehyde reaction drives the equilibrium toward formation of a stable covalent complex. Mallia (1992) found that adipic acid dihydrazide derivatization of periodate-oxidized dextran (containing multiple formyl functionalities) proceeds with much greater yield when sodium cyanoborohydride is present. 

Figure 14.25 The preparation of highly controlled fluorescent silica nanoparticles can be done by first polymerizing APTS that has been covalently modified with an amine-reactive dye to form fluorescent core particles. The core then is capped by a shell of silica by polymerization of TEOS. The shell layer can be further derivatized with silane coupling agents to provide functional groups for conjugation.

It has also been demonstrated that CNT sidewalls can be covalently fluorinated [148 150], or they can be derivatized with certain highly reactive chemicals such as dichlorocarbene [142], In this context, Chen et al. applied derivatization chemistry with thionychloride and octadecylamine in order to obtain organic soluble SWCNTs and later they performed a reaction with dichlorocarbene that led to the covalent functionalization of the nanotube walls. 

The indirect approach has been widely applied since many functional groups can be derivatized with various chiral reagents and the covalent diastereoisomers can be separated with inexpensive non-chiral systems. Other advantages of the indirect approach are that method development is rather straightforward and that the detection sensitivity of the enantiomers can be improved by the selection of an appropriate CDR having a strong chromophor or fluorophor. 

Polystyrene does not enable the covalent, reversible attachment of synthetic intermediates unless the support is derivatized with suitable functional groups. The most common groups for the reversible attachment of intermediates are chloromethyl and hydroxymethyl, whereas aminomethyl groups are mainly used as non-cleavable points of attachment for linkers (see Chapter 3). 

The analytes are separated by adsorption to a polar or nonpolar support surface or by partition into a stationary liquid phase. Silica is the most common polar adsorbent. HPLC basically involves the separation of compounds by partition on a stationary liquid phase, bonded to a support. The support, such as silica, is derivatized with a functional group that is covalently attached to the surface and is more stable than ary coated phase. Such bonded phases can be used with most solvents and buffers. A mobile liquid phase transports the sample into the column where individual compounds are selectively retained on the stationary liquid phase and thus separated. 

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