Department of Chemistry, Indian Institute of Science Education and Research, Bhopal By-Pass Road, Bhauri, Bhopal, 462 066, Madhya Pradesh, India.
Chem Asian J. 2021 Apr 19;16(8):966-973. doi: 10.1002/asia.202100139. Epub 2021 Mar 19.
The presence of a chalcogen atom at the ortho-position of phenols enhances their radical chain-breaking activity. Here, a copper(I)-catalyzed reaction of 2,6-dibromo- and 2,6-diiodophenols with diorganodiselenides has been studied for the introduction of two organoselenium substituents at both ortho-positions of the phenolic radical chain-breaking antioxidants, which afforded 2,6-diorganoseleno-substituted phenols in 80-92% yields having electron-donating CH , and electron-withdrawing CN and CHO functionalities. Additionally, 2,6-diiodophenols with electron-withdrawing CHO and CN groups also afforded novel 5,5'-selenobis(4-hydroxy-3-(phenylselanyl)benzaldehyde) and 5,5'-selenobis(4-hydroxy-3-(phenylselanyl)benzonitrile) consisting of three selenium and two phenolic moieties along with 2,6-diorganoseleno-substituted phenols has been synthesized. The electron-withdrawing CHO group has been reduced by sodium borohydride to the electron-donating alcohol CH OH group, which is desirable for efficient radical quenching activity of phenols. The developed copper-catalyzed reaction conditions enable the installation of two-arylselenium group ortho to phenolic radical chain-breaking antioxidants, which may not be possible by conventional organolithium-bromine exchange methods due to the sluggish reactivity of trianions (dicarba and phenoxide anion), which are generated by the reaction of organolithium with 2,6-dibromophenols, with diorganodiselenides. The antioxidant activities of the synthesized bis and tris selenophenols have been accessed by DPPH, thiol peroxides, and singlet oxygen quenching assay. The radical quenching antioxidant activity has been studied for the synthesized compounds by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The bis-selenophenols show comparable radical deactivating activity, while tris seleno-bisphenols show higher radical deactivating activity than α-tocopherol. Furthermore, the tris seleno-bisphenol shows comparable peroxide decomposing activity with ebselen molecules.
酚类化合物邻位上的杂原子的存在可以增强其自由基链断裂活性。在此，研究了铜（I）催化的 2,6-二溴和 2,6-二碘苯酚与二芳基二硒醚的反应，以在酚类自由基链断裂抗氧化剂的邻位上引入两个有机硒取代基，从而以 80-92%的产率得到具有给电子 CH 3 、吸电子 CN 和 CHO 官能团的 2,6-二芳基硒取代酚。此外，具有吸电子 CHO 和 CN 基团的 2,6-二碘苯酚还得到了新型的 5,5'-硒代双（4-羟基-3-（苯硒基）苯甲醛）和 5,5'-硒代双（4-羟基-3-（苯硒基）苯甲腈），它们由三个硒原子和两个酚部分组成，以及 2,6-二芳基硒取代酚。吸电子 CHO 基团已被硼氢化钠还原为给电子的醇 CH 3 OH 基团，这对于酚类物质的高效自由基猝灭活性是理想的。开发的铜催化反应条件允许在酚类自由基链断裂抗氧化剂的邻位上安装两个芳基硒基，这可能是不可能的，因为由有机锂与 2,6-二溴苯酚反应生成的三阴离子（二碳和苯氧阴离子）的反应性缓慢，与二芳基二硒醚反应。通过 DPPH、硫代过氧化物和单线态氧猝灭测定法来评估合成的双硒和三硒酚的抗氧化活性。通过 2,2-二苯基-1-苦基肼（DPPH）测定法研究了合成化合物的自由基猝灭抗氧化活性。双硒酚表现出相当的自由基失活活性，而三硒双酚比α-生育酚表现出更高的自由基失活活性。此外，三硒双酚的过氧化物分解活性与 ebselen 分子相当。
