Synthesis And Structure-property Relationships Study Of Some Diphenyl Ether Derivatives

Diphenyl ether and its derivatives with different substituents are widely used in the manufacture of agrochemicals, pharmaceuticals, spices and dyes. Many researches proved that diphenyl ether and its derivatives have been distributed all over the world and frequently detected in air, water, soil and food, damaging environment and the health of human and other organisms. Therefore, studying the environmental behavior and ecological risks of diphenyl ether derivatives has become important and attracted worldwide attention.In the present work, some diphenyl ether derivatives were studied, and the appropriate models were constructed. The main contents and the corresponding conclusions are as follows:(1) A synthetic route of polymethoxy diphenyl ethers was designed and optimized.27polymethoxy diphenyl ethers were synthesized with methoxy-iodobenzenes and methoxy-phenols as reagents by coupling reaction. Copper iodide as catalyst, cesium carbonate as base,1,2-did(dimethylamino) ethane as ligand, N,N-dimethylformamide as solvent, refluxing16h at130℃with N2protection. Infrared spectra (IR) and1H NMR spectra were adopted for structural identification of the samples synthesized, melting points were measured and high performance liquid chromatography was employed to determine the purities of the samples. Furthermore, the synthetic method of polyhydroxyl diphenyl ether was studied and the IR and1H NMR spectra of5products were also given.(2) Experimental and theoretical studies on Raman spectra, IR, and1H NMR of4,4’-oxybis(1-methoxybenzene) and4,4’-dihydroxydiphenyl ether have been worked out. The calculated values were consistent with the experimental results, which proved that the B3LYP/6-311G(d,p) method was feasible to predict the parameters and characteristics of structural-similar compounds.(3) We analyzed the spatial orientation of hydroxyl groups in polyhydroxyl diphenyl ethers (PHODEs), the type and strength of the intramolecular hydrogen bonds and the relative stability of PHODEs isomers. The standard enthalpies of formation (â–³fHθ) and the standard Gibbs energies of formation (â–³fGθ) of DE and209PHODEs were calculated with an isodesmic reactions. The quantitative structure-property relationships (QSPR) models between thermodynamic parameters (Sθ,â–³fHθå'Œâ–³fGθ) and the number and position of hydroxyl (NPHOS) were established, indicating these thermodynamic parameters all have close relationships with NPHOS· The first ionization constants (pKa{) of the synthesized compounds were determined using potentiometric titration experiments, together with the software ACD/Labs pKa DB program (version6.0). The compared results showed that the software could be used to predict the pKal of all209PHODEs.(4) Evaluation of4,4’-dihydroxydiphenyl ether,4,4’-difluorodiphenyl ether,4,4’-dichlorodiphenyl ethers and4,4’-dibromodiphenyl ether toxicity on adult and embryonic zebrafish was performed. The96h-LC50values demonstrated that they were of moderate toxicity to adult zebrafish. Moreover, the four compounds could cause the embryonic developmental toxicities, such as yolk sac edema, pericardial edema and spine deformation or tail curvature, and they also inhibited or delayed hatching and growth.