Synthesis organic solution phase

These libraries contain a relatively small number of individuals (typically tens to hundreds) and are almost always prepared as discrete libraries using parallel synthesis and automated or semiautomated devices. Focused libraries are predominantly prepared in solution because of the easier shift from classical organic synthesis to solution-phase combinatorial chemistry, while automated purification procedures for relatively small arrays of discrete compounds in solution are common nowadays. The... 

Among the other published works, Parlow et al. [60] and Xu et al. [61] reported the use of anion-exchange resins for the synthesis of solution-phase libraries of aryl and heteroaryl ethers via formation of a resin-bound phenol salt and its subsequent alkylation [60] (two pools of 10 compounds each) or with a one-pot procedure [61] (13 discretes). Polyme supported reagents being established tools in classical organic chemistry, their use for the synthesis of high-quality solution-phase libraries, possibly in combination with other solid-support-... 

In the 1990s the technique of solid-phase organic synthesis (SPOS) became generally popular, but especially in the medicinal chemistry community, for lead detection and lead optimization via combinatorial techniques. The combination with microwave irradiation brought an elegant solution for the problem of the notoriously slower reactions compared to those in solution phase. 

Soluble support-based synthetic approaches offer the advantages of both homogeneous solution-phase chemistry (high reactivity, ease of analysis) and solid-phase synthesis (large excess of reagents, simple product isolation and purification) [98,99]. As a representative example, PEG, one of the most widely used soluble polymers, has good solubility in most organic solvents (i.e., dichloromethane, acetonitrile, dimethylformamide, and toluene), but it... 

An important breakthrough in that respect was the use of soHd-phase organic synthesis (SPOS) where the attachment of the substrate to an insoluble support allowed for easy workup (filtration) and for rapid generation of products via split-mix procedures [1,2]. An important subsequent development consisted of the immobihzation of reagents, scavengers and catalysts. This technique, coined polymer-assisted solution phase chemistry (PASP), allowed solution phase synthesis of compoimds, yet still enjoying the bene-... 

DCC is a waxy solid that is often difficult to remove from a bottle. Its vapors are extremely hazardous to inhalation and to the eyes. It should always be handled in a fume hood. The isourea by-product of a DCC-initiated reaction, dicyclohexyl urea (DCU) (Figure 3.5), is also water-insoluble and must be removed by organic solvent washing. For synthesis of peptides or affinity supports on insoluble matrices this is not a problem, because washing of the support material can be done without disturbing the conjugate coupled to the support. For solution phase chemistry, however, reaction products must be removed by solvent washings, precipitations, or recrystallizations. 

Applications of the cross-metathesis reaction in more diverse areas of organic chemistry are beginning to appear in the literature. For example, the use of alkene metathesis in solution-phase combinatorial synthesis was recently reported by Boger and co-workers [45]. They assembled a chemical library of 600 compounds 27 (including cisttrans isomers) in which the final reaction was the metathesis of a mixture of 24 oo-alkene carboxamides 26 (prepared from six ami-nodiacetamides, with differing amide groups, each functionalised with four to-alkene carboxylic acids) (Eq.27). 

P. Wipf, Handbook of Reagents for Organic Synthesis Reagents for High Throughput Solid-Phase and Solution-Phase Organic Synthesis, Wiley, Chichester, 2005. 

B. Linclau, A. K. Singh, D. P. Curran, Organic-Eluorous Phase Switches A Fluorous Amine Scavenger for Purification in Solution Phase Parallal Synthesis , J. Org. Chem 1999, 64, 2835. 

An important tool for the fast characterization of intermediates and products in solution-phase synthesis are vibrational spectroscopic techniques such as Fourier transform infrared (FTIR) or Raman spectroscopy. These concepts have also been successfully applied to solid-phase organic chemistry. A single bead often suffices to acquire vibrational spectra that allow for qualitative and quantitative analysis of reaction products,3 reaction kinetics,4 or for decoding combinatorial libraries.5... 

DIC is a moderately expensive liquid that is employed in solid-phase synthesis to avoid the obstacles presented by the use of DCC. Both the reagent and the corresponding urea are soluble in organic solvents, and hence there is no bulky precipitate to contend with. The urea cannot be removed from an organic solution by aqueous extraction however, it is soluble enough in water that final traces can be removed from a precipitated peptide by washing the latter with a water-ether mixture. Clean up of spills of DIC can cause temporary blindness if utmost care is not exercised. 

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