Synthesis Of Polybrominated Diphenyl Ether Hydroxyl Metabolites And The Identification Of Related Unknown Contaminants

Polybrominated diphenyl ethers（PBDEs）are usually mixtures of tetra-,penta-,hexa-,octa-,and deca-brominated diphenyl ethers and are mostly used as flame retardants in plastics,textiles,coatings,and electronics.PBDEs are widely present in abiotic and biotic organisms and are persistent,biotoxic and bioaccumulative.It has been found that in living organisms,highly brominated diphenyl ethers undergo debromination,rearrangement of bromine atoms,and the introduction of hydroxyl or methoxy groups under the action of biometabolic enzymes.Such hydroxylated metabolites accumulate in human serum and cause multi-organ toxicity,especially disrupting thyroid hormone homeostasis.So far,limited studies are focused on lower brominated compounds and their hydroxylated metabolites（no more than seven bromine atoms）,and even less on highly brominated hydroxylated PBDEs（（Br7～Br9）HO-PBDEs）.That the synthesis of highly brominated HO-PBDEs are difficult due to the large steric hindrance between the bromination should be blamed.Therefore,the synthesis of highly brominated and hydroxylated PBDE specimens at high concentrations has become an important part of the research on this type of pollutants.The main contents of this thesis are as follows:1.A brief overview of the research progress of PBDEs and HO-PBDEs is presented.2.Five highly brominated（heptabromo and above）o-hydroxy polybrominated diphenyl ethers were designed and synthesized.Synthetic route I:Firstly,hydroxyl ortho-and para-bromination of 5-bromo-2-methoxyphenol gives 2,3,4-tribromo-6-methoxyphenol,then nucleophilic substitution with 3-bromo-4-fluoronitrobenzene to form PBDEs skeleton,then nitro reduction,amino ortho-bromination,diazotization-Sandmeyer reaction to achieve amino bromination,and finally,boron tribromide demethylation to obtain o-hydroxy PBDEs.Based on this route,two highly brominated o-hydroxy PBDEs,6-HO-BDE170 and 6-HO-BDE194 were synthesized.This route developed a new bromine source,where bromodimethyl-sulfonium bromide combined with DMSO and HBr to generate an electrophilic bromination of the aromatic ring,which is milder and more selective than the liquid bromine reaction,and greener and more environmentally friendly.Synthetic route II:The nucleophilic substitution of 5-fluoro-2-nitroaniline and 5-amino-2-methoxyphenol to form a PBDEs skeleton,the bromination of the ortho-and para-position of the amino group of the compound,followed by the diazotization of the two amino groups by HBr-Na NO₂ and the Sandmeyer reaction to bromine atoms,then the reduction of the nitro group,the bromination of the ortho-position of the amino group,and finally the demethylation of the boron tribromide and the bromination of the hydroxyl group to obtain three highly brominated o-hydroxy PBDEs,6′-HO-BDE177,6-HO-BDE195,and 6′-HO-BDE206.3.The synthesized target compound 6-HO-BDE194 was used as the standard sample for the quantitative analysis study of serum samples from three populations in an e-waste demolition area in southern China.The blood samples were processed and scanned by GC-MS in electron capture negative ionization（ECNI）mode with ion monitoring（SIM）to determine,the presence of 6-HO-BDE194 and to obtain the concentration of 6-HO-BDE194 in each blood sample by comparison with the retention time of the standard sample.Comparing the 6-HO-BDE194 concentrations in the blood samples of the three populations,it was found that the blood samples of e-waste dismantling workers contained higher 6-HO-BDE194 concentrations than those of the non-e-waste dismantling workers and the surrounding adult residents,indicating that more 6-HO-BDE-194 metabolites were produced in the bodies of people who were exposed to high exposure areas for a long time and bioaccumulated in the serum.