Synthesis Of Triazoles And Isoxazoles Using Poly (Etheylene Glycol) As Support

Recently, the techniques of soluble polymer support to synthesize small molecule libraries were applied successfully to combinatorial chemistry and parallel synthesis. Synthetic approaches that utilize soluble polymers termed liquid-phase chemistry, couple the advantages of homogeneous solution chemistry with those of solid phase methods. A series of triazoles and isoxazol(in)es have been synthesized by using poly(ethylene glycol) (PEG) 4000 as support in this paper. All reactions were highly efficient in giving the desired compounds in high yields and excellent purity by simple precipitation and wash, which suited the demand of parallel and combinatorial of small molecule libraries.Firstly, liquid-phase synthesis of triazoles using Poly (etheylene glycol) as support was described. PEG-supported alkyne reacted with halide, sodium azide to give PEG-supported triazoles by 1, 3-dipolar cycloaddition reaction, followed by cleavage from the resin, to give 1-aryl-4-hydromethyl- triazoles. Eight 1-aryl-4-hydro-methyl- triazoles were synthesized by this method. To our surprise Sonogashira reaction products were obtained.Secondly, liquid-phase synthesis of multisubstituted isoxazoles was developed by using PEG-supported nitrile oxide withα,β-unsaturated ketones. The polymer supported nitrile oxide reacted withα,β-unsaturated ketones to give polymer supported isoxazolines via 1, 3-dipolar cycloaddition reaction. After cleavage from the resin by CH3ONa/CH3OH, bisubstituted isoxazolines were obtained from non-aromaticα,β-unsaturated ketones as materials. However, 3, 4, 5-trisubstituted isoxazoles were obtained from aromaticα,β-unsaturated ketone. It means the cleavage companied the dehydrogenation...