Studies in the synthesis of benzoxazole compounds

[摘要] ENGLISH ABSTRACT: Benzoxazoles are an important class of π-electron-excessive, benzene-fused heterocycliccompounds found in natural products and display a wide range of pharmacological applications.It is therefore a widely used starting scaffold for drug and agrochemical discovery programs.Other applications include: chiral auxiliaries in asymmetric reactions, chiral receptors for theresolution of racemic mixtures, fluorescent whitening dyes, various photochromic materials andas ligands for a wide range of catalytic reactions. Due to our interests in resorcinarenes, wecame across 4-hydroxybenzoxazoles, a structural motif that has not been explored as potentialasymmetric ligands. In this thesis it was attempted to investigate the synthesis, functionalisationand coordination chemistry of these compound class and finally look at a method ofsynthesising chiral 4-hydroxybenzoxazoles from amino acids. A small library of achiral 4-hydroxybenzoxazoles were synthesised in good yields. Thesecompounds were then reacted with various transition metals, of which only the Pd-salts provedto return any usable compounds. The first structural evidence of the bonding of 4-hydroxybenzoxazoles was recorded from single crystal X-ray diffraction analysis of thecoordination compounds that formed. Different coordination modes were recorded, dependingon the ligand and the Pd-salt used. The PdCl2 compounds were also tested for catalytic activitywith a Heck reaction, showing good conversions for the reaction between iodobenzene andstyrene to form stilbene. Further examination pointed to the ligands playing an insignificant rolein the reaction and the products possibly due to only the PdCl2's reactivity.During this period it was also attempted to functionalise the phenol group with P(III) groups andrepeat the coordination and catalytic studies. Efforts to synthesise these compounds were notsuccessful, with oxidation of the P(III) to P(V) groups or degradation of these compounds.Efforts to synthesise these via phosphorous protection, utilising BH3 or the in situ trapping of thecompounds with transition metals, were also not successful. During the trapping experimentsthe phosphinite and Pd-salt formed a re-arranged product that is a known and useful catalyst onits own. Finally a small library of chiral benzoxazoles and 4-hydroxybenzoxazoles were synthesised,starting from amino acids and utilising a Mitsunobu reaction to perform the ring closing.Antimicrobial tests with these compounds did not return any appreciable results.

[发布机构] Stellenbosch University