Synthesis of Br(7)-Br(9) hydroxylated/methoxylated polybrominated diphenyl ethers (OH/MeO-PBDEs) and analyses on mass spectra and GC data of the MeO-PBDEs

Abstract

Previous studies have indicated that highly brominated diphenyl ethers may be oxidatively metabolized to OH-PBDEs and accumulated in human serum. However, identification of such metabolites has been hampered by a lack of reference standards. In the present study, we have developed a systematic approach for the preparation of Br7-Br9 OH-PBDEs with various substitution patterns. The approach involved a coupling reaction between 5-fluoro-2-nitroaniline and a methoxyphenol or aminomethoxyphenol to produce diphenyl ethers, subsequent bromination of these diphenyl ethers, removal of the amino/nitro groups, and/or conversion of amino/nitro groups to bromo substituents. The amino group was the key to our approach; it facilitated regioselective bromination on the phenyl rings and could then be removed or readily replaced by a bromo substituent. In total, 25 MeO-PBDEs and 20 OH-PBDEs were successfully synthesized, demonstrating the feasibility and versatility of this approach. The characteristics of the mass spectrometric fragmentations of the MeO-PBDEs have been investigated and are discussed herein. In addition, the relative retention times of these MeO-PBDEs relative to BDE-118 on three columns with different polarities have been determined.