Polymer-Assisted Solution-Phase Organic Synthesis

Polymer-Assisted Solution-Phase Organic Synthesis 

In this chapter we summarize results from our work on RD catalysts, which we started in the early 1980s [11, 24, 25, 35-43]. The concept of polymer/carrier materials in the shape of Raschig rings, rods, discs, or other shapes has demonstrated its benefits in a number of applications. Starting from the requirements for RD 

Reactive distillation Reactive stripping Large scale reactors 

4 Rock, K. Smith, L. Chen, J., in AIChE Spring Meeting, New Orleans, Louisiana, USA, 29 March, 1992. 

17 Andllotti, E. Massi Mauri, M. Pescar-ollo, E. Romagnoni, L. J. Mol. Catal. 1978, 4, 37-48. 

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For a solution-phase parallel synthesis to be efficient, a complete conversion of reactants to product with little or no formation of by-products or impurities is required. Here the concept of solid-phase-assisted solution-phase organic synthesis comes into play. The important characteristic to have in mind about polymer-assisted solution-phase organic synthesis... 

Polymer-Assisted Solution-Phase Organic Synthesis... 

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-... 

In this chapter we discuss the new speeding-up techniques, optimized during the last decade, such as solid-phase extraction, polymer-assisted solution-phase synthesis, microwave-assisted organic synthesis, and flow chemistry. The improvements obtained with these techniques are not limited to a subset of chemical reactions (e.g., the reported examples), but they are fully applicable to the entire set of chemistry involved in the synthetic drug discovery process. 

Linclau B, Sing AK, Curran DP. Organic-Fluorous phase switches a fluorous amine scavenger for purification in solution phase parallel synthesis. J Org Chem. 1999 64 2835-2842. Parlow JJ. Polymer-assisted solution-phase chemical library synthesis. Curr. Opin. Drug Discov. Devel. 2005 8 757-775. 

Li, X., AbeU, C., Warrington, B.H. and Ladlow, M. (2003) Polymer-assisted solution phase synthesis of the antih3fperglycemic agent Rosiglitazone (Avandia ). Organic and Biomolecular Chemistry, 1, 4392-4395. 

However, it was not until Merrifield developed a polystyrene matrix for peptide synthesis that a broad range of functionalized solid supports became available [91], leading to solid phase organic synthesis (SPOS) and eventually to polymer-assisted solution synthesis (PASS). Both of these techniques are heavily utilized by industry, especially for rapid library synthesis. 

Many laboratories have investigated alternative solution-phase strategies for preparing combinatorial libraries to overcome these limitations of solid-phase organic synthesis.This chapter reviews advances that have been made over the last two years in polymer-assisted syntheses. This... 

The field of organic chemistry has seen the most extensive use of polymeric materials as aids in effecting chemical transformation and product isolation. Insoluble polymer supports have been used as handles to facilitate these functions. As chemical reagents can be bound to an insoluble polymer carrier and used in organic synthesis [117,118], polymer-bound reagents can also be used to assist in the purification step of solution-phase reactions [119,120]. The latter are known as scavenger resins. These are added to the reaction mixture upon completion of the reaction in order to quench and selectively bind to the unreacted reagents or by-products. The polymer-bound impurities are then removed firom the product by simple filtration to obtain pure compounds. For example, aminomethylated poly(styrene-co-divinyl benzene) can be used to remove acid chlorides, sulfonyl chlorides, isocyanates, thiocyanates, and proton. Similarly, 2-Chlorotrityl resins have been developed for the attachment of carboxylic acids, alcohols. 

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