Synthesis of esters
The Steglich Esterification is a mild reaction, which allows the conversion of sterically demanding and acid labile substrates. It's one of the convenient methods for the formation of tert-butyl esters because t-BuOH tends to form carbocations and isobutene after a subsequent elimination under the conditions employed in the Fischer Esterification.
Mechanism of the Steglich Esterification
DCC (dicyclohexylcarbodiimide) and the carboxylic acid are able to form an O-acylisourea intermediate, which offers reactivity similar to the corresponding carboxylic acid anhydride:
The alcohol may now add to the activated carboxylic acid to form the stable dicyclohexylurea (DHU) and the ester:
In practice, the reaction with carboxylic acids, DCC and amines leads to amides without problems, while the addition of approximately 5 mol-% DMAP is crucial for the efficient formation of esters.
N-Acylureas, which may be quantitatively isolated in the absence of any nucleophile, are the side products of an acyl migration that takes place slowly. Strong nucleophiles such as amines react readily with the O-acylisourea and therefore need no additives:
A common explanation of the DMAP acceleration suggests that DMAP, as a stronger nucleophile than the alcohol, reacts with the O-acylisourea leading to a reactive amide ("active ester"). This intermediate cannot form intramolecular side products but reacts rapidly with alcohols. DMAP acts as an acyl transfer reagent in this way, and subsequent reaction with the alcohol gives the ester.
Simple Method for the Esterification of Carboxylic Acids
B. Neises, W. Steglich, Angew. Chem. Int. Ed., 1978, 17, 522-524.
A Sequential Acyl Thiol-Ene and Thiolactonization Approach for the Synthesis of δ-Thiolactones
R. O. McCourt, E. M. Scanlan, Org. Lett., 2019, 21, 3460-3464.