Jourdan-Ullmann reaction

What is Jourdan-Ullmann reaction?

The Jourdan-Ullmann condensation is a copper-catalyzed reaction between aryl halides and aniline, which results in the formation of diarylamines in the presence of a base. This reaction was first reported by Jourdan in 1885, who observed the reaction between aniline and activated aryl halides. Ullmann extended this reaction in 1902 to include unactivated or slightly activated aryl halides using copper or copper reagents as a catalyst and K2CO3 as the base. Goldberg, Ullmann’s assistant and wife, further extended this reaction from acetanilide to form diarylamines, regardless of the degree of activation of the aryl halides.

Jourdan-Ullmann reaction - general reaction scheme - Ullmann condensation - Ullmann-Goldberg coupling - Ullmann-Jourdan reaction
Jourdan-Ullmann reaction
  • X = Cl, Br, I
  • R1, R2 = H, alkyl, aryl, NO2, CN, COOH, etc.

The Jourdan-Ullmann condensation is also known as the Ullmann condensation, Ullmann-Goldberg coupling, and Ullmann-Jourdan reaction. The reactivity of aryl halides with electron-withdrawing groups is higher than those with electron-donating substituents. The reactivity of halides follows the order:

I > Br > Cl > F

In comparison, anilines with electron-withdrawing groups generally proceed poorly in this reaction, except for some specific reaction pairs.

Copper acetate, cuprous iodide, and pure copper metal in the presence of oxygen are all effective catalysts for this reaction. Other metal salts, such as iron, nickel, platinum, and zinc, are also active catalysts. However, the salts of tin and manganese are inactive reagents. The addition of a base such as K2CO3 is critical for this reaction because it neutralizes the generated hydrogen halide, and it also converts the carboxyl group into carboxylate for certain reactions, which reduces the chance for decarboxylation and minimizes the resinous by-products.

The heterogenous Jourdan-Ullmann reaction proceeds slowly in general, but the application of high-boiling aprotic solvents containing oxygen, nitrogen, and sulfur atoms facilitates the reaction by partially converting it into a homogenous reaction due to coordination. Mono-ether of ethylene glycol and its oligomers have shown considerable advantages as solvents for this condensation, due to their different boiling points, ability to accelerate the reaction rate, and miscibility with water, which simplifies the workup process. However, all solvents used for this reaction must be dry because existing water may coordinate with copper and deplete the active catalyst.

Additionally, under the conditions of the Jourdan-Ullmann condensation, many other nucleophiles can also couple with aryl halides, but this reaction suffers from high reaction time and the need for a large excess of copper or copper salts. Moreover, this reaction is often accompanied by reductive dehalogenation of aryl halides.