Synthesis of 2-(4-chlorophenyl)-2-(4-chloro-3-thiophenol)-1,1-dichloroethene (3-SH-DDE) via Newman-Kwart rearrangement - a precursor for synthesis of radiolabeled and unlabeled alkylsulfonyl-DDEs.
For the first time, a pathway for synthesis of 2-(4-chlorophenyl)-2-(4-chloro-3-thiophenol)-1,1-dichloroethene (3-SH-DDE), is presented. The compound is of particular interest as a precursor for synthesis of alkylsulfonyl-DDE containing different alkyl groups to discover structural activity relationships, and to promote synthesis of radiolabeled methylsulfonyl-DDE. 2-Chloro-5-methylphenol was first methylated and further oxidized to the corresponding benzoic acid. The acid was reduced to the corresponding aldehyde (4-chloro-3-methoxy benzaldehyde) via 4-chloro-3-methoxy-benzene methanol. A lead/aluminium bimetal system was used to carry out the reductive addition of tetrachloromethane to 4-chloro-3-methoxy benzaldehyde to obtain 2,2,2-trichloro-1-(4-chloro-3-methoxyphenyl)ethanol, the desired starting material to synthesize the DDT-analogue (2-(4-chlorophenyl)-2-(4-chloro-3-methoxy-phenyl)-1,1,1-trichloroethane). Elimination of hydrochloric acid and removal of the methyl group led to the 3-OH-DDE. The Newman-Kwart rearrangement was applied to convert 3-OH-DDE to 3-SH-DDE via the dimethylcarbamothioate derivative. 3-SH-DDE is then used as a precursor for the radiolabel synthesis. The overall yield to acquire 3-SH-DDE after 11 steps was 3%. The step with the lowest yield was the DDT-analog synthesis with a yield of 30%. All other step had a yield of >50%. 3-SH-DDE was methylated with (14)C-labeled iodomethane and oxidized by hydrogen peroxide to obtain 3-[(14)C]MeSO(2)-DDE in an overall yield of 30%.
Cantillana
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T
Department of Environmental Chemistry, Stockholm University, SE-10691 Stockholm, Sweden. tatiana@mk.su.se
Sundström
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M
Bergman
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A
D003633:Dichlorodiphenyl Dichloroethylene / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D007306:Insecticides / Q000138:chemical synthesis* / Q000737:chemistry; D007553:Isotope Labeling; D008939:Mitotane / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry
C544535:2-(4-chlorophenyl)-2-(4-chloro-3-thiophenol)-1,1-dichlorethene; D007306:Insecticides; D003633:Dichlorodiphenyl Dichloroethylene; D008939:Mitotane