No abstract

No abstract

A new macroporous stationary phase bearing 'tweezer' receptors that exhibit specificity for cholesterol has been constructed from rigid multifunctional vinylic monomers derived from 3,5-dibromobenzoic acid, propargyl alcohol and cholesterol. The synthesis of the novel tweezer monomer that contains two cholesterol receptor arms using palladium mediated Sonogashira methodologies and carbonate couplings is reported. The subsequent co-polymerisation of this tweezer monomer with a range of cross-linking agents via a 'pseudo' molecular imprinting approach afforded a diverse set of macroporous materials. The selectivity and efficacy of these materials for cholesterol binding was assessed using a chromatographic screening process. The optimum macroporous stationary phase material composition was subsequently used to construct monolithic solid phase extraction columns for use in the selective extraction of cholesterol from multi-component mixtures of structurally related steroids. {Electronic supplementary information (ESI) available: synthetic procedures and analytical data for compounds 3-8. See

No abstract

The efficient synthesis of rigid multifunctional vinylic monomers 1 and 2 from 3,5-dibromobenzene derivatives and propargyl alcohol via the Sonogashira reaction is reported. For example, a series of 3,5-bis(3-hydroxyprop-1-ynl)benzoate ester derivatives have been prepared efficiently using an improved palladium catalyst system. Subsequent hydrolysis and reaction with 4-vinylaniline afforded a new monomer 2 for use in functional macroporous polymer systems. In addition, Sonogashira and Wittig methodologies have been optimised in order to construct successfully an alternative rigid monomer 1 from 3,5-dibromobenzaldehyde.The palladium(0)/copper(I) halide catalysed coupling of terminal alkynes with aryl or alkenyl halides, first reported 1 by Sonogashira and co-workers, is a widely used method for the synthesis of arylalkynes and conjugated enynes. 2 As part of our research towards the synthesis of novel rigid vinylic monomers 1 and 2 ( Figure) for use in imprinted polymer systems, 3 an efficient and robust procedure for the coupling of propargyl alcohol to a range of 3,5-dibromobenzene derivatives was required. Consequently, use of Sonogashira coupling methodologies was investigated and the results of these studies are reported herein.The synthesis of monomer 1 employed the conditions reported 4 by Brown et al. for the synthesis of 3,5-dibromobenzaldehyde from 3,5-dibromobenzoic acid via a two step reduction/selective oxidation process (Scheme 1). Employing the original reaction conditions described 1 by Sonogashira and co-workers (0.4 mol% Pd (PPh 3 ) 2 Cl 2 , 0.8 mol% CuI, triethylamine, THF) in conjunction with 3,5-dibromobenzaldehyde and propargyl alcohol, the key intermediate 3,5-bis(3-hydroxyprop-1-yl)benzaldehyde 3 was constructed in good yield (Table, entry 1). The hydroxyl moieties of 3 were then protected in the form of their corresponding tert-butyldimethylsilyl (TBDMS) ethers. Subsequent conversion of the aldehyde group of the protected diol 4 to the corresponding olefin 5 employing standard Wittig conditions 5 followed by deprotection of the TBDMS groups afforded the desired monomer 1 in 96% yield.In addition to monomer 1, novel rigid monomers such as 2 ( Figure), comprised of 3,5-bis-acetylenated aromatic units tethered to a polymerisable vinylic group, were also targeted to enable structure-property relationships of the resultant imprinted polymers to be studied. The approach used to obtain monomers such as 2 also involved use of the palladium mediated cross-couplings of propargyl alcohol to 3,5-dibromobenzoic acid ethyl ester (Scheme 2). However, in stark contrast to monomer 1, the synthesis of monomer 2 required significant modification of the Sonogashira-based methodologies.Under the original coupling conditions (Table, entry 2), the desired bis-acetylenic product 6a was not isolated, only a moderate yield of mono-substituted product 7a was obtained. This effect has also been observed 6 by Krause and co-workers in the coupling of trimethylsilylacetylene to methyl bromobenzoate derivatives and highe...