Horenstein-Pählicke reaction

What is Horenstein-Pählicke reaction?

The Horenstein-Pählicke reaction, also known as the Horenstein-Pählicke process or Horenstein-Pählicke condensation, involves the reaction between a substituted aryl carboxylic acid and N,N-dialkylamino alkyl halide to produce N,N-dialkylaminoalkyl arylcarboxylate hydrochloride.

The Horenstein-Pählicke reaction was first reported in 1938 by Horenstein and Pählicke and is particularly useful for preparing a group of molecules with anesthetic activity.

Horenstein-Pählicke reaction - general reaction scheme - Horenstein-Pählicke process - Horenstein-Pählicke condensation
Horenstein-Pählicke reaction

The use of a benzyl group instead of an acetyl group for protection of the hydroxyl group in the aryl carboxylic acid can increase the yield of the reaction. The Horenstein-Pählicke reaction is typically carried out in isopropanol or butanol n-BuOH in the presence of a base such as K2CO3. The use of butanol as a solvent generally results in higher yields than isopropanol, and direct reaction between the aryl carboxylic acid and alkyl halide can give even higher yields. However, this reaction is more effective with primary alkyl halides and is not ideal for secondary alkyl halides. The Horenstein-Pählicke reaction is often performed in dry toluene under basic conditions.

References

Horenstein, H. and Pählicke, H. (1938), Über eine neue Umlagerungsreaktion und ihre Anwendung zur Darstellung von Estern der Aminoalkohole. [On a new rearrangement reaction and its application to the preparation of esters of aminoalcohols.] Ber. Dtsch. Chem. Ges. A/B, 71: 1644-1657. https://doi.org/10.1002/cber.19380710820

Shares