Synthesis of chlorinated and non-chlorinated biphenyl-2,3- and 3,4-catechols and their [2H3]-isotopomers

• Published in: Organic & biomolecular chemistry 2004-09, Vol.2 (18), p.2624-2629
• Main Authors: Lin, Po-Hsiung, Sangaiah, R, Ranasinghe, Asoka, Ball, Louise M, Swenberg, James A, Gold, Avram
• Format: Article
• Language: English
• Subjects: Biphenyl Compounds - chemical synthesis; Biphenyl Compounds - chemistry; Catechols - chemical synthesis; Catechols - chemistry; Isomerism; Magnetic Resonance Spectroscopy; Mass Spectrometry; Molecular Structure; Polychlorinated Biphenyls - chemical synthesis; Polychlorinated Biphenyls - chemistry
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/b409373a

A synthetic scheme is described for chlorinated biphenyl-2,3- and 3,4-catechols to be used as standards for structural assignment of metabolites and protein adducts of 2,2',5,5'-tetrachlorobiphenyl in which both rings retain chlorine substituents. The scheme has general applicability to the synthesis of chlorinated biphenyl catechols. Dimethyl catechol ethers are coupled to dichloroaniline via the Cadogan reaction to give a library of isomers, followed by demethylation of the ethers with BBr3 to yield the target catechols. Separation of pure isomers is accomplished by TLC or HPLC prior to or following demethylation, depending on the isomer mixture. [2H3]-Isotopomers are generated using 2,5-dichloroaniline-d3 as the starting arylamine in the coupling reaction. The dichloroaniline-d3 hydrochloride is obtained as the sole product from nitration of p-dichlorobenzene-d4 followed by Pd/C-catalyzed hydrogenation under strongly acidic conditions. This hydrogenation procedure provides a simple and convenient approach to selective reduction of aryl nitro groups in the presence of halogen ring substituents.