Synthesis of substituted diphenylamines and carbazoles: phototransformation products of diclofenac

Abstract

The formation of stable and potentially hazardous compounds as a result of photochemical transformation of pharmaceutical substances in the aquatic environment implies a demand for standard compounds within environmental analysis. The major phototransformation products of diclofenac are comprised of substituted diphenylamines and carbazoles. Substituted diphenylamines were synthesized by Ullmann condensation reactions between anilines and halobenzenes. Monochlorocarbazoles were obtained from palladium-catalyzed intramolecular coupling reactions of monochlorinated diphenylamines, photocyclization of dichlorinated diphenylamines or by direct chlorination of carbazole. The availability of synthetic photoproducts of diclofenac is of critical importance for further studies on the environmental fate as well as the ecotoxicological effects of the drug in the environment.

A Photochemical Study of Diclofenac and Its Major Transformation Products

“…The aim of this paper was to conduct a kinetic study of the aqueous photochemical transformation of diclofenac and its major transformation products (TPs) (8‐chloro‐9H‐carbazol‐1‐yl) acetic acid (Cz1), 2‐(2‐chloro‐phenylamino)‐benzaldehyde (Ald) and (1,4‐dioxo‐4,9‐dihydro‐1H‐carbazol‐8‐yl) acetic acid (Cz4). In addition, identification of transformation products, either through access to synthesized standard compounds (14) or by NMR analysis of isolated products, is emphasized.…”

Electrochemical Determination of Diclofenac Sodium in Aqueous Solution on Cu‐Doped Zeolite‐Expanded Graphite‐Epoxy Electrode

“…. These species with very high reactivity, generated by anodic evolution of a hydroxide ion at copper oxide sites as intermediate of oxygen evolution, could generate the formation of ortho-substitued diphenylamines and carbazoles, reported as transformation products of diclofenac [3].…”

“…In recent years, the growing use of pharmaceuticals has initiated a considerable concern regarding their presence in the environment [1][2][3]. Sodium diclofenac(DCF), sodium[o-(2,6-dichloroanilino) phenyl] acetate, is a widely used anti-inflammatory drug, which exhibits anti-inflammatory, analgesic and antipyretic activities, and can be regarded as a representer of a novel class of water pharmaceuticals contaminants, because it has been found in many wastewater treatment plants effluents [4].…”

Oxidation of diclofenac by potassium ferrate (VI): Reaction kinetics and toxicity evaluation

“…During the phototransformation process, the major byproducts of DCF are composed of substituted diphenylamines and carbazoles, which are of critical importance for further studies on the ecotoxicological effects of the drug in the ambient environment (Svanfelt and Kronberg, 2011). Although DCF was rapidly degraded during drinking water disinfection using free chlorine, it may generate chlorinated disinfection byproducts (Soufan et al, 2012).…”