a halogen or pseudohalogen is initiated by a one-electron transfer mechanism catalyzed by copper(I) to form an aryl radical with loss of nitrogen gas. The substituted arene is possibly formed by direct transfer of Cl, Br, CN, or OH from a copper(II) species to the aryl radical to produce the substituted arene and regenerate the copper(I) catalyst. In an alternative proposal, a transient copper(III) intermediate, formed from coupling of the aryl radical with the copper(II) species, undergoes rapid reductive elimination to afford the product and regenerate copper(I). However, evidence for such an organocopper intermediate is weak and mostly circumstantial, and the exact pathway may depend on the substrate and reaction conditions. These possibilities are shown below. Generation of the nitrosonium ion Formation of the benzenediazonium ion Single electron transfer Synthetic applications Variations on the Sandmeyer reaction have been developed to fit multiple synthetic applications. These reactions typically proceed through the formation of an aryl diazonium salt followed by a reaction with a copper(I) salt to yield a substituted arene according to the scheme below. Some examples of the synthetic applications of the Sandmeyer reaction are provided below. Halogenation One of the most important uses of the Sandmeyer reaction is the formation of aryl halides. The solvent of choice for the synthesis of iodoarenes is diiodomethane, while for the synthesis of bromoarenes, bromoform is used. For the synthesis of chloroarenes, chloroform is the solvent of choice. The synthesis of (+)-curcuphenol, a bioactive compound that displays antifungal and anticancer activity, employs the Sandmeyer reaction to substitute an amine group by a bromo group. One bromination protocol employs a Cu(I)/Cu(II) mixture with additional amounts of the bidentate ligand phenanthroline and phase-transfer catalyst dibenzo-18-crown-6 to convert an aryl diazonium tetrafluoroborate salt to an aryl bromide. The Balz–Schiemann reaction uses tetrafluoroborate and delivers the halide-substituted product, fluorobenzene, which is not obtained by the use of copper fluorides. This reaction displays motifs characteristic of the Sandmeyer reaction. Cyanation Another use of the Sandmeyer reaction is for cyanation which allows for the formation of benzonitriles, an important class of organic compounds. A key intermediate in the synthesis of the antipsychotic drug Fluanxol is synthesized by a cyanation through the Sandmeyer reaction. The Sandmeyer reaction has also been employed in the synthesis of neoamphimedine, a compound that is suggested to target topoisomerase II as an anti-cancer drug. Trifluoromethylation It has been demonstrated that Sandmeyer-type reactions can be used