Polymer-supported Reactions Research Articles

Microwave-assisted oxidative coupling of thiols using polystyrene supported bromoderivatives of 2-oxazolidone

Polymer-supported reagents have become popular in synthetic organic chemistry over the past decades. But the kinetics of polymer-supported reactions is slow compared to solution phase synthesis because of the poor diffusion of the reactants through the macromolecular polymer matrix. This difficulty can be reduced to a great extent by performing polymer-supported reactions under microwave (MW) conditions. The present work is focussed on the design and development of an innovative, powerful, MW stable and recyclable polymeric reagent prepared by attaching bromoderivative of 2-oxazolidone into the macromolecular matrix of polystyrene. 3% cross-linked polystyrene was prepared by free radical aqueous suspension polymerization technique using tetra ethylene glycol diacrylate as the cross-linking agent and the resulting beads were functionalized by chloromethylation followed by reaction with 2-oxazolidone. Bromine functionality is introduced into the polymer by treating with bromine in carbon tetrachloride. The synthetic utility of the prepared polymeric reagent was demonstrated by the oxidative coupling of thiols to disulfides under MW irradiation. No over oxidation was observed in this protocol and the utilization of polystyrene support simplifies work up and product isolation. The synthesised polymeric reagent displayed good cyclic stability up to five cycles without any substantial decrease in bromine content and satisfactory storage stability under normal laboratory condition. Moreover this may be the first report that uses MW energy for the oxidation of thiols to disulfides using polymer-supported reagents. [Formula: see text]

David Colin Sherrington. 5 March 1945—4 October 2014

David Colin Sherrington began life as a Liverpool docker's son and became an internationally recognized authority on reactive polymers and using polymer-supported reagents in novel applications. His research career began at University of Liverpool with his PhD work on the mechanisms of cationic polymerization. From 1972 until retirement in 2010, Strathclyde University was his chief research base. In the very early years he continued with mechanistic and kinetic studies of cationic polymerization, but soon moved to the field of polymer-supported reactions and reagents, to which he devoted the rest of his research career. An important contribution to the direction of his scientific activity was the secondment years he spent at Unilever, where he became involved in polymeric high internal phase emulsions (polyHIPEs). In the following years, he devoted much effort to accurate characterization of these and other porous polymer supports, frequently involving him in learning new techniques (e.g. neutron scattering). An important feature was the use of polymer supports to catalyse oxidation reactions, especially olefin epoxidation. He gained valuable insight into many aspects of his research from the many visiting professorships over his career. He was involved on the editorial board of Reactive Polymers continuously from 1982 until 2010 and he was awarded many honours. His free time was mainly devoted to fishing, particularly for salmon, an activity he shared with his wife and a group of friends for many years. His warmth, intellect and clear interest in the careers of his research students were key components in creating the polymer ‘family’ to which they belonged. His years of retirement were saddened by multiple system atrophy, a devastating illness throughout which he was cared for by Val, his wife.

Parallel and Combinatorial Liquid-Phase Synthesis of Alkylbiphenyls Using Pentaerythritol Support

Unfunctionalized alkylbiphenyls were fabricated by a parallel and combinatorial synthesis using pentaerythritol as a tetrapodal soluble support for a sulfonate-based traceless multifunctional linker system. Nickel N-heterocyclic carbene-catalyzed reactions of pentaerythritol tetrakis(biphenylsulfonate)s with primary alkylmagnesium bromides generated the alkylbiphenyl derivatives by desulfitative cleavage/cross-coupling of the C-S bond without any "memory" of the attachment on the support. Though the reactions were completed with sufficient yields in 12 h at room temperature, even with only 1.5 equiv of nucleophiles, they still retained the benefits of facile isolation observed in polymer-supported reactions.

Solid-phase asymmetric synthesis using a polymer-supported chiral Evans'-type oxazolidin-2-one

This protocol describes the synthesis of (S)-4-(4-hydroxybenzyl)-oxazolidin-2-one, its attachment to a Merrifield-Cl resin and its use for asymmetric synthesis. The chiral auxiliary is prepared in four steps from N-Boc-L-tyrosine on a multigram scale in high yield and attached to Merrifield-Cl resin via its phenolic group to afford a solid-supported chiral auxiliary for asymmetric synthesis that takes ∼7 d to prepare. A procedure for its N-acylation is reported and a method for carrying out diastereoselective solid-supported Evans' syn-aldol reactions is described, with aldol products being cleaved from the polymer by either hydrolysis or reduction. The use of the supported auxiliary for two sequential 'on-bead' reactions has been demonstrated for the synthesis of a chiral cyclopropane aldol and a γ-lactone in a >95:5 diastereomeric ratio. These polymer-supported reactions are carried out in IRORI Kan resin capsules to protect the polymer support from mechanical degradation, thus allowing multiple on-bead reactions to be performed.

Soluble polymer supported divergent synthesis of tetracyclic benzene-fused pyrazino/diazepino indoles: an advanced synthetic approach to bioactive scaffolds

The synthesis of indoline substituted nitrobenzene on a PEG support and its further elaboration to structurally diverse benzene-fused pyrazino/diazepino indoles is disclosed. A reagent based diversification approach coupled with Pictet-Spengler type condensation reactions furnished these fused polycyclic scaffolds. Microwave irradiation was used as a means of rate acceleration for soluble polymer-supported reactions. The efficiency of these fused heterocyclic molecules to inhibit the vascular endothelial growth factor receptor 3 (VEGFR-3) was examined in vitro using kinase receptor activation enzyme-linked immunosorbant assay (KIRA-ELISA). Based on the preliminary results obtained, a small set of potential drug candidates were identified as novel leads in this therapeutic area to be further explored as anti-metastatic agents.

Traceless Liquid-Phase Synthesis of Biphenyls and Terphenyls Using Pentaerythritol as a Tetrapodal Soluble Support

Application of a novel sulfonate-based traceless multifunctional linker system using pentaerythritol as a tetrapodal soluble support was demonstrated using liquid-phase parallel and combinatorial preparation of biphenyl and terphenyl compounds. Nickel-catalyzed reactions of pentaerythritol tetrakis(arenesulfonate)s with arylmagnesium bromides generated the desired products in sufficient yields through reductive cleavage/cross-coupling of the C-S bond. Homogeneous pentaerythritol-supported reactions could be accomplished using less nucleophile with shorter reaction periods than could the corresponding heterogeneous polymer-supported reactions. This liquid-phase approach using a small polyfunctionalized support combines advantages of solution-phase and solid-phase syntheses by allowing high reactivity, high atom economy, simple isolation, and real-time monitoring of the reaction progress.

Understanding Supported Reactions in Spherical Compartments: A General Algorithm To Model and Determine Rate Constants, Diffusion Coefficients, and Spatial Product Distributions

A general algorithm allowing the numerical modeling of the time and space dependence of product formation in spherical reaction volumes is described. The algorithm is described by the complete set of mass balance equations. On the basis of these equations, the effects of the diffusion coefficient, reaction rate, bead size, reagent excess, and packing density of the resin beads on the overall reaction rates are determined for second-order reactions. Experimental data of reaction progress are employed to calculate reaction rates and diffusion coefficients in polymer-supported reactions. In addition, the conditions for shell-like product formation are determined, and various strategies for the radial patterning of resin beads are compared. The effect of diffusion on polymer-supported enzyme-catalyzed reactions of the Michaelis-Menten type is treated, as well. Finally, the effects of typical nonideal solid-phase phenomena, namely, the inhomogeneity of rate constants and the concentration dependence of diffusion coefficients, on overall rates are discussed.

A Polymer-Supported Organic Reaction: Seeing Is Believing

Polymer-supported reactions have recently been shown to provide an important alternative approach to preparing organic compounds. Whereas traditional solution-phase syntheses can involve lengthy workup procedures leading to the isolation of organic products, the use of solid polymer supports considerably simplifies this process and products are recovered by filtration and washing procedures. These types of reactions can be used in combinatorial chemistry to prepare large numbers of compounds both quickly and efficiently. This method has found particular application in the pharmaceutical industry. However, the progress of reactions on polymer supports can be difficult to follow and, for example, thin-layer chromatography cannot be used if the starting material and product are covalently bound to the polymer. One simple method for determining the progress of reactions on polymer supports involves the use of chemical stains. These selectively react with certain functional groups to form highly-colored products. In this laboratory experiment, an amide-coupling reaction is carried out on a polymer support, and the reaction is monitored using different chemical stains. This effectively demonstrates, through color changes, the reaction of a polymer-supported amine that provides students with valuable practical experience of this important and modern advance in organic chemistry methodology.

No-carrier-added (n.c.a.) synthesis of asymmetric [73,75Se]selenoethers with isonitriles.

A new synthetic pathway for the preparation of no-carrier-added (n.c.a.) [73.75Se]selenoethers was investigated in order to enlarge the scope of available radioselenated compounds. Starting from n.c.a. 73,75Se(0), an isonitrile and an amine, the preparation of appropriate disubstituted radioselenoureas via homogenous and polymer-supported reactions was examined. Alkylation of these intermediates yielded the corresponding [73-75S]selenouronium salts. Hydrolysis under basic conditions provided the [73,75Se]alkylselenolates and a subsequent alkylation yielded various asymmetric [73-75Se]selenoethers with radiochemical yields of 13-56% within a reaction time of 130min in the homogenous phase and 35 min using the polymer-supported synthesis.

Liquid-phase combinatorial reaction monitoring by conventional 1H NMR spectroscopy

The application of 1H NMR spectroscopy for complete analysis of soluble polymer-supported reactions is described. This conventional analytical technique enables us to determine the extent of liquid-phase reactions without cleavage of the soluble matrix. The polymer matrix permitted us to obtain 1H NMR spectra with a resolution comparable with that of spectra of the molecule in solution.

Exploring the scope of poly(ethylene glycol) (PEG) as a soluble polymer matrix for the Stille cross-coupling reaction.

The optimization and efficient parallel synthesis and purification of a library of biaryl, heterobiaryl, and styryl derivatives, via the first reported poly(ethylene glycol)-supported palladium-catalyzed Stille procedure, are described. Preliminary investigations into the reaction between monomethoxy poly(ethylene glycol)5000-supported iodide 1a with tributylphenyltin 2 revealed that the optimal "liquid-phase" conditions employ PdCl2(PPh3)2 (0.1 equiv) catalysis with LiCl (10 equiv) in DMF at 80 degrees C for either 48 h (at 20 mM concentration of 1a) or 24 h (at 10 mM concentration of 1a). The soluble polymer-supported reaction is superior to its solution-phase counterpart because the tributyltin side products and excess reagents are easily separated from the product intermediate 3a by precipitation of 3a into diethyl ether followed by recovery of the polymer by filtration in > 99%. In addition, the homocoupled byproduct 6 is also removed during this precipitation step. Under these conditions the transesterified biaryl adduct 4a can be isolated in 97-98% yield. The scope of this reaction was probed in a parallel format with the PEG-supported electrophiles 1a-b and a range of tributyl stannanes 2 and 7-13 under the optimized conditions vide supra. Subsequent cleavage of the polymer-supported adducts, by transesterification, and short column chromatography yielded a library of substituted methyl benzoates 4a-b and 14a-b to 20a-b in high yield (69-99%) and purity (> 95%).

Analysis of cyclic oligomers of poly(ethylene terephthalate) by liquid chromatography/mass spectrometry

Cyclic oligomers [CO · C 6H 4 · CO · O · CH 2 · CH 2 ·O] x (with x = 3–8) of poly(ethylene terephthalate) have been prepared by a polymer-supported reaction. They have been investigated by field desorption mass spectrometry and liquid chromatography/mass spectrometry. The particular stability of the cyclic trimer x = 3 is demonstrated by the results.

Polymer-supported organic reactions: what takes place in the beads?

The use of polymer-supported reactants in organic synthesis is currently of considerable interest, especially in the context of combinatorial syntheses. To carry out successfully reactions using polymer-supported reactants it is important to be aware of what takes place inside the beads. Examples are presented in this article which show that compared to the analogous homogeneous reactions systems, polymer-supported reactions can show substrate selectivity, be slower or faster, follow a different reaction course, or give a significantly different stereochemical result.

Cyclic polyesters: 1. Preparation by a new synthetic method, using polymer-supported reagents

A new method of synthesizing cyclic polyesters is described, using polymer-supported reactions. This method involves the attachment of Ω-bromocarboxylate anions to the surface of an ion-exchange resin, followed by polymerization and cyclization by inter- and intramolecular alkylation reactions, respectively. The polymerization reaction results in the formation of oligomeric chain polyester molecules that remain bound to the resin by the carboxylate anion end group. The cyclization reaction results in the detachment of the cyclic product from the resin support. The cyclic polyester [(CH 2) 10CO.O] x obtained was divided into a series of sharp fractions using preparative g.p.c. and each fraction was examined by analytical g.p.c. The cyclic nature of the polyester product was established by n.m.r. spectroscopy and by fast atom bombardment (f.a.b.) mass spectrometry. The f.a.b. mass spectrum of a fraction showed a series of spectral lines corresponding to [(CH 2) 10CO.O] x with x = 2–7. The cyclic products were directly compared with analogous linear polymers.

Polymer-supported reaction and further expansion

Polymer-supported reaction and further expansion

3rd international conference on polymer-supported reactions in organic chemistry concluding remarks

3rd international conference on polymer-supported reactions in organic chemistry concluding remarks

3rd International conference on polymer-supported reactions in organic chemistry a personal assessment

3rd International conference on polymer-supported reactions in organic chemistry a personal assessment

3rd International conference on polymer-supported reactions in organic chemistry Opening remarks

3rd International conference on polymer-supported reactions in organic chemistry Opening remarks

ChemInform Abstract: Polymer‐Supported Reactions: Synthesis of Phenacyl Esters of Phenoxyacetic Acids.

ChemInformVolume 18, Issue 33 Preparative Organic Chemistry ChemInform Abstract: Polymer-Supported Reactions: Synthesis of Phenacyl Esters of Phenoxyacetic Acids. S. D. MAHAJAN, S. D. MAHAJAN Dep. Chem., Univ. Calif., Santa Barbara, CA 93106, USASearch for more papers by this authorR. B. MANE, R. B. MANE Dep. Chem., Univ. Calif., Santa Barbara, CA 93106, USASearch for more papers by this authorM. H. JAGDALE, M. H. JAGDALE Dep. Chem., Univ. Calif., Santa Barbara, CA 93106, USASearch for more papers by this authorM. M. SALUNKHE, M. M. SALUNKHE Dep. Chem., Univ. Calif., Santa Barbara, CA 93106, USASearch for more papers by this author S. D. MAHAJAN, S. D. MAHAJAN Dep. Chem., Univ. Calif., Santa Barbara, CA 93106, USASearch for more papers by this authorR. B. MANE, R. B. MANE Dep. Chem., Univ. Calif., Santa Barbara, CA 93106, USASearch for more papers by this authorM. H. JAGDALE, M. H. JAGDALE Dep. Chem., Univ. Calif., Santa Barbara, CA 93106, USASearch for more papers by this authorM. M. SALUNKHE, M. M. SALUNKHE Dep. Chem., Univ. Calif., Santa Barbara, CA 93106, USASearch for more papers by this author First published: August 18, 1987 https://doi.org/10.1002/chin.198733124AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume18, Issue33August 18, 1987 RelatedInformation

Second international meeting on polymer-supported reactions in organic chemistry

Second international meeting on polymer-supported reactions in organic chemistry