Ullmann condensation

In the Ullmann condensation or Ullmann-type reaction is the copper-promoted conversion of aryl halides to aryl ethers, aryl thioethers, aryl nitriles, and aryl amines. These reactions are examples of cross-coupling reactions. In the Ullmann condensation or Ullmann-type reaction is the copper-promoted conversion of aryl halides to aryl ethers, aryl thioethers, aryl nitriles, and aryl amines. These reactions are examples of cross-coupling reactions. Ullmann-type reactions are comparable to Buchwald-Hartwig reactions but usually require higher temperatures. Traditionally these reaction requires 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. Aryl halide were required to be activated by electron-withdrawing groups. Traditional Ullmann style reactions used 'activated' copper powder, e.g. prepared in situ by the reduction of copper sulfate by zinc metal in hot water. The methodology improved with the introduction of soluble copper catalysts supported by diamines and acetylacetonate ligands. Illustrative of the traditional Ullmann ether synthesis is the preparation of p-nitrophenyl phenyl ether from 4-chloronitrobenzene and phenol. Modern arylations use soluble copper catalysts. A traditional Goldberg reaction is illustrated by the synthesis of fenamic acid, an intermediate in the preparation of acridone: Aryl iodides are favored arylating agents. The catalyst used is formed from copper(I) iodide and phenanthroline. As this reaction proceeds well with an electron-rich aryl iodide it is a valuable alternative to the Buchwald–Hartwig amination reaction, which gives best yields with electron-poor aryl halides. The scope is extended to amides. The nucleophile can also be carbon as in a carbanion as well as cyanide. In the traditional Hurtley reaction, the carbon nucleophiles were derived from malonic ester and other dicarbonyl compounds: More modern Cu-catalyzed C-C cross-couplings utilize soluble copper complexes containing phenanthroline ligands. The arylation of alkylthiolates proceeds by the intermediacy of cuprous thiolates.