Oxidative Halogenation with “Green” Oxidants: Oxygen and Hydrogen Peroxide

Abstract

It is difficult to imagine organic chemistry without organo-halogen compounds and the molecular halogens needed for their preparation. The halogens have very different reactivity, with iodine usually requiring some form of activation, while others are reactive and hazardous chemicals. To avoid their use, various modified reagents have been discovered (N-bromo- and N-chlorosuccinimide, Selectfluor..), but halogens are used to prepare these reagents and when they are used the atom economy is poor. A better approach, which is based on biomimetric research on oxidative halogenation in nature, consists of generating the halogenating reagent in situ under acidic conditions from a halide salt. The result of such a reaction has been halogenation with 100 % halogen atom economy. Suitable oxidants for the oxidation of halides are hydrogen peroxide and oxygen.

A sustainable two-phase procedure for V-catalyzed toluene oxidative bromination with H2O2–KBr

“…1 Furthermore, these molecules find applications in the field of materials science, pharmaceuticals, agrochemicals and bioactive compounds. 2 In a general sense, halogenation is an oxidative process carried out efficiently in nature through enzyme-catalysed reactions where a halide ion is transformed into a halogenating intermediate.…”

“…5c, 7a As a logical development, we decided to explore this procedure also for functionalization of toluene at the benzylic position. Bromination in the side chain of aromatic derivatives has been performed with several acid systems containing bromide and an oxidant, 1,8 eventually in the presence of light. 8 Also some dibromo disulfonamides have been proposed as effective brominating agents for toluene.…”

Recent advances in vanadium catalyzed oxygen transfer reactions

“…Organic bromo-derivatives are important precursors for various selective and efficient transformations in organic synthesis, as industrial intermediates and pharmaceuticals. Hazards and environmental problems correlated with classical bromination methods have encouraged the attention towards the development of safer and environmentally friendlier methods [55]. In this contest vanadium haloperoxidases (VHPOs), which have been isolated mainly from marine algae and fungi, have received much attention because they are able to catalyze the oxidation of halides to the corresponding hypohalous acid using hydrogen peroxide as primary oxidant [56].…”

Regioselective Arene Halogenation using the FAD‐Dependent Halogenase RebH

“…[5] Oxidative methods to catalytically generate halogenating agents from halide salts have been developed, but none of these have solved the aforementioned selectivity problem, and few utilize oxygen as a terminal oxidant (Scheme 1). [6] New, more efficient methods for oxidative halogenation would significantly improve the syntheses of a wide range of chemicals and are therefore highly desirable. [6] Given the high efficiency and selectivity often associated with enzyme-catalyzed reactions, we were drawn to several classes of enzymes that catalyze oxidative halogenation reactions.…”

“…[6] New, more efficient methods for oxidative halogenation would significantly improve the syntheses of a wide range of chemicals and are therefore highly desirable. [6] Given the high efficiency and selectivity often associated with enzyme-catalyzed reactions, we were drawn to several classes of enzymes that catalyze oxidative halogenation reactions. [7] Particularly notable in this regard are the FAD-dependent halogenases, which were first characterized by van Pée and coworkers in the late 1990's.…”