Solid-phase organic synthesis solvents

Solvents for Microwave-Assisted Solid-Phase Organic Synthesis... 

There are only few examples for oxidation reactions on solid supports, because most linkers or polymeric supports are sensitive towards some reagents suitable for classical transformations. Classical oxidation reagents are not soluble in most solvents used in the solid-phase organic synthesis step (but e.g. Scheme 3.10). 

Solid-phase organic synthesis refers to syntheses in which the starting material and synthetic intermediates are linked to an insoluble material (support), which enables the facile mechanical separation of the intermediates from reactants and solvents (Figure 2.1). 

Several different support materials have proven useful for solid-phase organic synthesis, but not all materials are compatible with all types of solvents and reagents. Therefore, for each application the proper type of support has to be selected. Some review articles on supports for solid-phase synthesis have recently appeared [1,9, 12-15]. 

In this section the use of polystyrene and copolymers of styrene with various cross-linking agents as supports for solid-phase organic synthesis is discussed. Copolymers of styrene with divinylbenzene are the most common supports for solid-phase synthesis. Depending on the kind of additives used during the polymerization and on the styrene/divinylbenzene ratio, various different types of polystyrene can be prepared. However, non-cross-linked polystyrene has also been used as a support for organic synthesis [10,16-22], Linear, non-cross-linked polystyrene is soluble in organic solvents such as toluene, pyridine, ethyl acetate, THF, chloroform, or DCM, even at low temperatures, but can be selectively precipitated by the addition of methanol or water. 

Different forms of silicon dioxide have been used as supports for solid-phase organic synthesis. Silica gel is a rigid, insoluble material, which does not swell in organic solvents. Commercially available silica gel differs in particle size, pore size (typically 2-10 nm), and surface area (typically 200-800 m2/g). Like macroporous, highly cross-linked polystyrene, silica gel enables efficient and rapid transfer of solvents and reagents to its entire surface. Because the synthetic intermediates are only located on the surface of the support, enzyme-mediated reactions can be realized on silica [189,190], Silica gel is particularly well suited for continuous-flow synthesis because its volume stays constant and diffusion rates are high. 

Chemistry on soluble polymer matrices has recently emerged as a viable alternative to solid-phase organic synthesis (SPOS) involving insoluble cross-linked polymer supports. Separation of the functionalized matrix is achieved by solvent or heat precipitation, membrane filtration, or size-exclusion chromatography. Suitable soluble polymers for liquid phase synthesis should be crystalline at room temperature, with functional groups on terminal ends or side chains, but must not be not cross-linked they are therefore soluble in several organic solvents. 

In triphase catalysis, solvated resin supports are important carriers for solid-phase organic synthesis in combinatorial chemistry. The physical properties of resin, resin swelling, dynamic solvation, and solvated supports are important factors in affecting the synthesis. However, these factors are also affected by solvent. Selective solvation of resin alters the local reactivity and accessibility of the bound substrate and the mobility of the entrapped re-... 

Solid phase organic synthesis without using any solvent. 

Solid Phase Organic Synthesis Without Using Any Solvent... 

The following gives a brief account of solid phase organic synthesis without the use of any solvent. 

A method has been developed that enables solid phase organic synthesis to be performed in microtiter wells not equipped with any kind of porous material at the bottom to facilitate the separation of solid resin beads from a solvent. The concept of washing resin beads in the Don Cucna synthesizer was developed by the need for a reliable and fast operational cycle applicable to a hundred reaction vessels at the same time. The simplest compact reaction block for solid phase synthesis is the 96-well plate. The suction (aspirating) principle of the Don Cucna synthesizer is based on the fact that in most solvents used in solid phase synthesis the resin beads settle to the bottom of the wells of the plates. The settling of the resin is relatively fast (tens of seconds). After the resin beads have settled, stainless-steel needles connected to an evacuated waste container are slowly immersed into the wells of a plate (Fig. 8). The needles remove the liquid from above the surface of the resin without disturbing the resin bed. For washing the resin beads in 96-well microtiter plates, two... 

Since most aaAAs are hydrophobic in nature, peptides rich in aaAAs are generally restricted to study in organic solvents due to their low solubility in aqueous media. There have been very few examples of side-chain functionalized aaAAs that would allow for the synthesis of highly water-soluble peptides rich in aaAA content.3 This is primarily due to difficulty of synthesis, since side-chain functionalized derivatives must be orthogonally protected to allow for incorporation into solid-phase peptide synthesis. The harsh conditions, under which standard methods of aaAA synthesis are performed, make this a difficult task. 

---