Steglich esterification

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The Steglich esterification is a variation of an esterfication with dicyclohexylcarbodiimide as a coupling reagent and 4-dimethylaminopyridine as a catalyst. The reaction was first described by Wolfgang Steglich in 1978.[1] It is an adaptation of an older method for the formation of amides by means of DCC (dicyclohexylcarbodiimide) and 1-hydroxybenzotriazole (HOBT).[2][3]

Steglich overview

This reaction generally takes place at room temperature. A suitable solvent is dichloromethane. Because the reaction is mild, esters can be obtained that are inaccessible through other methods for instance esters of the sensitive 1,4-dihydroxybenzoic acid. A characteristic is the formal uptake of water generated in the reaction by DCC, forming the urea compound dicyclohexylurea (DCU).

Reaction mechanism[edit]

The reaction mechanism is described as follows:

  • The carboxylic acid reacts with DCC to an O-acyl isourea, which is more reactive than the free acid

Mechanism Steglich reaction part 1

  • The alcohol attacks this intermediate, forming DCU and the corresponding ester

Steglich reaction overview

With amines, the reaction proceeds without problems to the corresponding amides because amines are more nucleophilic. If the esterification is slow, a side-reaction occurs, diminishing the final yield or complicating purification of the product. This side-reaction is a 1,3-rearrangement of the O-acyl intermediate to a N-acyl urea which is unable to further react with the alcohol

To suppress this reaction, DMAP is added, acting as an acyl transfer-reagent in the following manner:

Action of DMAP in the Steglich esterfication

References[edit]

This article incorporates information from the German Wikipedia.
  1. ^ B. Neises, W. Steglich (1978). "Simple Method for the Esterification of Carboxylic Acids". Angew. Chem. Int. Ed. 17 (7): 522–524. doi:10.1002/anie.197805221. 
  2. ^ J. C. Sheehan, G. P. Hess (1955). "A New Method of Forming Peptide Bonds". J. Am. Chem. Soc. 77 (4): 1067–1068. doi:10.1021/ja01609a099. 
  3. ^ W. König, R. Geiger (1970). "Eine neue Methode zur Synthese von Peptiden: Aktivierung der Carboxylgruppe mit Dicyclohexylcarbodiimid unter Zusatz von 1-Hydroxy-benzotriazolen". Chem. Ber. 103 (3): 788–798. doi:10.1002/cber.19701030319. 

Further reading[edit]

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