Wohl-Ziegler reaction

What is Wohl-Ziegler reaction?

The Wohl-Ziegler reaction is a bromination of unsaturated organic compounds at either allylic or benzylic position (or α-position of the side chain of other aromatic compounds) using N-bromosuccinimide (NBS) as the bromination reagent. This reaction was first reported by Wohl in 1919 using N-bromoacetamide as the bromination reagent, which resulted in a very low yield of allylic bromide and was subsequently improved by Ziegler who introduced NBS as the bromination reagent in 1942. Therefore, the bromination by N-bromoacetamide is simply referred to as the Wohl reaction, whereas the bromination by NBS is generally known as the Wohl-Ziegler bromination, or Wohl-Ziegler reaction. Occasionally, this reaction is also referred to as the Wohl-Ziegler radical bromination.

The Wohl-Ziegler reaction is typically performed by adding an alkyllithium reagent, such as n-butyllithium or sec-butyllithium, to a halide or pseudohalide compound in the presence of a polar solvent, such as ether or THF. The alkyllithium reagent acts as a nucleophile, attacking the electrophilic carbon atom of the halide or pseudohalide compound and forming a lithium halide compound..

Wohl-Ziegler reaction - general reaction scheme
Wohl-Ziegler reaction
Wohl-Ziegler reaction - general reaction scheme
Wohl-Ziegler reaction

The lithium halide compound is then eliminated through the loss of a proton, resulting in the formation of an alkyl group in place of the halide or pseudohalide. The Wohl-Ziegler reaction is typically used to synthesize primary and secondary alkyl compounds, but it can also be used to synthesize tertiary alkyl compounds under certain conditions..

The Wohl-Ziegler reaction is a useful method for the synthesis of alkyl compounds. For example, the synthesis of alkylbenzene carboxylic acids and phenols, benzyl alcohols, and benzylic ethers. However, it has several limitations, including the need for highly reactive alkyllithium reagents and the formation of unwanted byproducts. As a result, it has largely been superseded by other methods, such as the Grignard reaction and the Corey-House reaction..

It should be noted that the Wohl-Ziegler reaction is not a very efficient reaction and often requires high pressure and temperature to run the reaction, which can lead to unwanted side reactions. Additionally, the Wohl-Ziegler reaction is not selective and can lead to the formation of multiple products depending on the reaction conditions..

Summary

The Wohl-Ziegler reaction is a valuable method for the synthesis of alkyl compounds, but it has largely been replaced by more modern and efficient methods. Despite this, it remains an important part of the history of chemistry and continues to be studied by chemists today..

Example

The reaction involves the oxidation of the alkylbenzene using a combination of bromine (Br2) and aluminum isopropoxide Al(Oi-Pr)3 as the catalysts.

The general equation for the Wohl-Ziegler reaction is:

Alkylbenzene + Br2 + Al(Oi-Pr)3 → Alkylbenzene carboxylic acid + HBr

For example, the Wohl-Ziegler reaction of toluene (methylbenzene) with bromine and aluminum isopropoxide produces benzoic acid:

C6H5CH3 + Br2 + Al(Oi-Pr)3 → C6H5COOH + HBr

Mechanism of reaction

The Wohl-Ziegler bromination proceeds via a radical mechanism. Initially, the reaction was proposed to involve a succinimidyl radical. However, more evidence indicates that the molecular bromine, generated from NBS and hydrogen bromide, is the active brominating reagent that is maintained at a low concentration level. Moreover, since NBS and succinimide are rather insoluble in CCl4, it is possible that the reaction involving succinimidyl radical propagation occurs on the surface of NBS crystals. The combination of proposed mechanisms is given here for a general allylic bromination, where a small amount of HBr may exist in NBS or form due to a trace amount of moisture in the reaction system.

Wohl-Ziegler reaction mechanism
Reaction mechanism of Wohl-Ziegler reaction

The mechanism of the Wohl-Ziegler reaction involves several steps, starting with the formation of a complex between the alkylbenzene, bromine and aluminum isopropoxide. The overall process can be summarized in three main steps:

  • Initiation: The first step is the formation of a complex between the alkylbenzene, bromine and aluminum isopropoxide. The bromine acts as a Lewis acid and coordinates with the aluminum isopropoxide to form a bromonium ion intermediate, which is a species with a positive charge on the bromine atom. The alkylbenzene then coordinates with the bromonium ion intermediate, forming a complex..
  • Propagation: The next step is the propagation of the reaction by the formation of a carbocation intermediate. The complex formed in step 1 undergoes a nucleophilic attack by the bromide ion (Br), which acts as a nucleophile. This leads to the formation of a carbocation intermediate and the release of a bromide ion (Br)..
  • Termination: The final step is the termination of the reaction by the formation of the alkylbenzene carboxylic acid and hydrogen bromide (HBr). The carbocation intermediate formed in step 2 undergoes an electrophilic attack by the bromine molecule, leading to the formation of the alkylbenzene carboxylic acid and HBr..

Overall, the Wohl-Ziegler reaction is a bromination of the alkylbenzene followed by an oxidation of the intermediate brominated species using bromine and aluminum isopropoxide to form the alkylbenzene carboxylic acid.

References

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