Ullmann Reaction

Ullmann Coupling

The Ullmann reaction, also called Ullmann coupling, is an organic reaction that is used to couple two molecules of aryl halide for forming a biaryl with the help of copper metal and thermal conditions. The mechanism for the Ullmann reaction is not entirely understood, however, there are two popular mechanisms. The radical mechanism includes the single electron transfer from the copper metal to the alkyl halide for forming an aryl radical. Two aryl radicals then react and form the final biaryl product. The second mechanism includes an oxidative addition of the copper to the aryl halide and is followed by a single electron transfer and forms an organocuprate reagent. The organocuprate then performs another oxidative addition on an aryl halide and reductive elimination takes place that results in the final biaryl product. In this article, we will learn about the Ullmann reaction, Ullmann reaction mechanism, and the Ullmann reaction application.

Ullmann Coupling Reaction Mechanism

As mentioned, there are two different Ullmann coupling mechanisms. Both are shown as follows:

  1. Radical mechanism

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  1. Mechanism involving the aryl copper intermediate

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Mechanism of Ullmann Reaction in Detail

Let us now take a look at the mechanism in detail.

  1. Step 1:

The mechanism of the Ullmann reaction includes the formation of an active copper(I) species when the aryl halide is introduced to an excess of metallic copper under very high temperatures, above 200C.

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  1. Step 2:

The resulting copper(I) species further undergoes oxidative addition with another haloarene molecule and links the two molecules.

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  1. Step 3:

In the final step of the Ullmann coupling mechanism, the copper compound which is formed by the two aryl halide molecules undergoes a reductive elimination and results in the formation of a new carbon-carbon bond between both the aryl compounds.

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Role of Copper in Ullmann Reaction

The Ullmann reaction is a metal-catalyzed coupling of halogene-benzene derivatives which leads to biaryls (an aryl group is a group obtained by removing a hydrogen atom from and aromatic compound; if the aromatic compound is benzene, the aryl is the phenyl group) and the larger carbon-based structures. This reaction offers an unprecedented opportunity for accessing the molecular functionality by improving the mechanical stability and electron conductance, that is essential for the advancement in the realization of organic-based electronics.

Catalysts, like copper, provide an alternative pathway through which the reaction can proceed, in which the activation energy is slightly lower. It thus increases the rate at which the reaction comes to the equilibrium. The catalyst itself takes part in the reaction without undergoing any permanent chemical change, although it can undergo a physical one. In the classical Ullmann reaction, the oxidation of copper along with the formation of molecular cuprate intermediates and copper halides as side reaction products precedes the cross-coupling reaction. However, there is general agreement that at a certain point of the reaction a copper-coordinated structure is formed, the debromination mechanism, that is the rate-limiting step of the reaction, has been scarcely investigated. At this point, it is not clear whether the formation of radicals or organo-copper complexes or the oxidative addition process precedes the formation of the biaryl compound.

Ullmann Reaction Application

Now that you know about the Ullmann coupling reaction, its nomenclature, the mechanism of the reaction and the importance of copper in the reaction, let us have a look at the applications of the Ullmann reaction.

The Ullmann reaction applications are as follows:

  1. Biphenylenes are obtained from 2, 2- diiodo biphenyl through the Ullmann reaction.

  2. Ullmann reaction can also be used for the closure of the five-membered rings.

  3. An unsymmetrical reaction can be achieved when one of the reactants is provided in excess.

  4. Chiral reactants are coupled into a chiral product through the Ullmann coupling reaction.

Significance of Ullmann Reaction

The Ulmann reaction has its own significance when it comes to the organic chemistry. Let us now look at what it is. 

The Ullmann coupling reaction has become a powerful and essential tool in the organic synthesis and drug discovery. Copper-catalyzed Ullmann reactions were very well developed recently by employing the novel ligands and ancillary synthetic tools. Amongst the many exciting and rapid developments of the Ullmann coupling reactions, its is believed that the green synthetic methodologies, such as metal-, ligand-, and additive-free conditions, recyclable heterogeneous catalysts, and microwave-assisted synthesis will continue to have a significant impact on this field. 

FAQ (Frequently Asked Questions)

1. What is the Ullmann Coupling reaction?

The Ullmann reaction, also called an Ullmann coupling reaction, is an organic reaction which involves the coupling of the two aryl halides in the presence of copper to result into a biaryl as the product. The Ullmann coupling reaction is named after the German chemist named Fritz Ullmann. The general equation of the Ullmann reaction is shown below.

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2. What are non symmetric and asymmetric couplings in the Ullmann coupling reaction?

Ullmann synthesis of the biaryl compounds are used for the generation of the chiral products from chiral reactants. Nelson and collaborators worked on this synthesis of the asymmetric biaryl compounds and obtained a thermodynamically controlled product.

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The diastereomeric ratio of these products is enhanced with the bulkier R groups in the auxiliary oxazoline group. The unsymmetrical Ullmann reactions are very rarely pursued but are achieved when any one of the two coupling components is in excess quantity.

3. What is the type of solvent used in the Ullmann reaction?

In the Ullmann reaction, a highly polar non-aqueous solvent such as the dimethyl formamide (DMF) is used. Sometimes if one of the reagents used is a liquid, then the reaction has been carried out even without using any other solvents.