Voigt condensation

What is Voigt condensation?

The Voigt condensation, also known as the Voigt reaction, was discovered by Voigt in 1886. It involves the condensation of a primary amine or a secondary amine with a benzoin in the presence of phosphorus pentoxide P2O5 or hydrochloric acid HCl to form a secondary or tertiary α-aminoketone.

Voigt condensation - general reaction scheme
Voigt condensation

Steric hindrance can affect the success of this reaction, making it more effective for primary amines. Phosphorus pentoxide P2O5 is commonly used as the condensation reagent. However, primary amines with high steric hindrance, such as tri-(hydroxymethyl)methylamine and 2-amino-1,3-dihydroxymethyl-2-methylpropane, do not undergo this reaction, and simple secondary amines, like diethylamine, do not react due to steric hindrance.

Cyclic secondary amines, such as pyrrolidine and piperidine, readily react with benzoins to produce corresponding tertiary aminoketones. Electron density on both benzoins and amines can also affect the Voigt condensation. An electron-donating group on the benzoins impedes the reaction, and 4-methoxybenzoin reacts less readily with secondary amines than benzoin due to its carbonyl group being less electron deficient.

Voigt condensation requires an α-proton and is not possible without it, resulting in the direct replacement of the hydroxyl group by the amino group, which is difficult. The Meerwein-Ponndorf-Verley reduction, using aluminum isopropoxide, can be used to convert the resulting aminoketones into α-amino alcohols. Only one stereoisomer is typically isolated after the reduction of most α-amino ketones, except for α-piperidyldesoxybenzoin.

References

Voigt, K., J. Prakt. Chem., 1886, 34, 2

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