In 2022,Yin, Honglu; Chen, Yuepeng; Zhong, Qiu; Zheng, Shilong; Wang, Guangdi; He, Ling published an article in Bioorganic & Medicinal Chemistry Letters. The title of the article was 《Design, synthesis, and antitumor study of a series of novel 1-Oxa-4-azaspironenone derivatives》.Electric Literature of C7H6BrCl The author mentioned the following in the article:
A series of 1-oxa-4-azaspiro[4,5]deca-6,9-diene-3,8-dione derivatives containing structural fragments of conjugated dienone have been synthesized previously by authors’ group, however the Michael addition reaction between conjugated dienone and nucleophilic groups in the body may generate harmful and adverse effects. To reduce harmful side effects, the authors started with p-aminophenol to make 1-oxo-4-azaspirodecanedione derivatives I (R1 = 4-MeC6H4, 2-ClC6H4, 4-BrC6H4, etc.) then utilized the Michael addition and cyclopropanation to synthesize target compounds II (R1 = 4-Me, 4-ClC6H4, 3-ClC6H4, 4-BrC6H4; R2 = CH(COOMe)2), III (R1 = 4-MeC6H4, 4-ClC6H4, 2,6-Cl2C6H3; R2 = CH3CH2S) and IV (R1 = 4-O2NC6H4, 2-ClC6H4, 4-BrC6H4, etc.) in order to eliminate α, β unsaturated olefinic bond and lower the Michael reactivity of the compounds in vivo for optimization. At the same time, heteroatoms are put into the mols. in order to improve the hydrophilicity of the mols. and the binding sites of the mols. and the target mols., establishing the groundwork for improved antitumor activity. The majority of the compounds had moderate to potent activity against A549 human lung cancer cells, MDA-MB-231 breast cancer cells, and Hela human cervical cancer cells. Among them, II (R1 = 3-ClC6H4; R2 = CH(COOMe)2) showed the strongest effect on A549 cell line with IC50 of 0.26μM; IV (R1 = 2-ClC6H4) showed the strongest cytotoxicity on MDA-MB-231 cell line with IC50 of 0.10μM; and II (R1 = 3-ClC6H4; R2 = CH(COOMe)2) showed the strongest activity on Hela cell line with IC50 of 0.18μM. In the experiment, the researchers used many compounds, for example, 1-(Bromomethyl)-4-chlorobenzene(cas: 622-95-7Electric Literature of C7H6BrCl)
1-(Bromomethyl)-4-chlorobenzene(cas: 622-95-7) undergoes carbonylation in the presence of dimer of chloro(1,5-cyclooctadiene)rhodium(I) to yield the corresponding phenylacetic acid.Electric Literature of C7H6BrCl It can be synthesized by reacting 4-chlorobenzyl alcohol with bromodimethylsulfonium bromide (BDMS) It can also be synthesized by refluxing a mixture of 4-chlorobenzaldehyde, chlorotrimethylsilane, 1,1,3,3-tetramethyldisiloxane and lithium bromide.
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics