One-electron oxidation of chloroquine, cymanquine, and related aminoquinolines in nonaqueous media

The anodic oxidation of a series of secondary-amine-substituted chloroquinoline derivatives, 1–5, has been studied in dichloromethane/0.05 M [NBu₄][B(C₆F₅)₄]. Compounds 4 and 5 contain organometallic moieties of the cymantrene family as part of the amine group. All five compounds undergo an electrochemically irreversible one-electron oxidation. For compounds 2–4, this occurs at the secondary amine group (0.86 to 0.98 V vs ferrocene). The oxidations of others occur at tertiary amines located either in the side chain of the quinoline secondary amine (1, 0.68 V) or in the cyclopentadienyl ring of the cymantrene moiety (5, 0.82 V). The anodic reaction products have been isolated and shown to be ring-nitrogen protonated aminochloroquinolinium ions. Abstraction of a hydrogen atom from the solvent by the putative aminochloroquinoline radical cation is thought to be responsible for formation of the protonated oxidation product. Cathodic reduction of the latter regenerates the neutral starting material in an overall chemically reversible process that mimics a simple acid/base reaction at the quinoline ring nitrogen.