Steglich esterification

This article will address Steglich esterification, a topic that has captured the attention and interest of numerous people in recent years. Steglich esterification has become a topic of relevance in today's society due to its impact in different areas, such as culture, politics and the economy. Throughout this article, the different aspects related to Steglich esterification will be explored, analyzing its causes, consequences and possible solutions. The historical evolution of Steglich esterification will be examined, as well as its influence on contemporary society. Likewise, different perspectives and approaches on Steglich esterification will be presented, with the aim of offering a comprehensive and enriching vision on this topic of general interest.
Steglich esterification
Named after Wolfgang Steglich
Reaction type Coupling reaction
Identifiers
Organic Chemistry Portal steglich-esterification

The Steglich esterification is a variation of an esterification 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
Steglich overview

This reaction generally takes place at room temperature. A variety of polar aprotic solvents can be used.[4] Because the reaction is mild, esters can be obtained that are inaccessible through other methods for instance esters of the sensitive 2,4-dihydroxybenzoic acid. A characteristic is the formal uptake of water generated in the reaction by DCC, forming the urea compound dicyclohexylurea (DCU).

Reaction mechanism

The reaction mechanism is described as follows:

Mechanism Steglich reaction part 1

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 an N-acylurea which is unable to further react with the alcohol. DMAP suppresses this side reaction, acting as an acyl transfer-reagent in the following manner:

Action of DMAP in the Steglich esterification

References

  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. PMID 5436656.
  4. ^ Jordan, Andrew; Whymark, Kyran D.; Sydenham, Jack; Sneddon, Helen F. (2021). "A solvent-reagent selection guide for Steglich-type esterification of carboxylic acids". Green Chem. 23 (17): 6405–6413. doi:10.1039/D1GC02251B.

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