Traditionally, these reactions require high-boiling, polar solvents such as N-methylpyrrolidone, nitrobenzene, or dimethylformamide and high temperatures (often in excess of 210 °C) with stoichiometric amounts of copper.
The methodology improved with the introduction of soluble copper catalysts supported by diamines and acetylacetonate ligands.
The coupling of 2-chlorobenzoic acid and aniline is illustrative:[4] A typical catalyst is formed from copper(I) iodide and phenanthroline.
In the traditional Hurtley reaction, the carbon nucleophiles were derived from malonic ester and other dicarbonyl compounds:[6] More modern Cu-catalyzed C-C cross-couplings utilize soluble copper complexes containing phenanthroline ligands.
[1] These copper(I) compounds subsequently react with the aryl halide in a net metathesis reaction: In the case of C-N coupling, kinetic studies implicate oxidative addition reaction followed by reductive elimination from Cu(III) intermediates (Ln = one or more spectator ligands):[9] The Ullmann ether synthesis is named after its inventor, Fritz Ullmann.