The Steglich esterification is a variation of an
esterification
In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ar ...
with
dicyclohexylcarbodiimide as a coupling reagent and
4-dimethylaminopyridine as a
catalyst
Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...
. The reaction was first described by
Wolfgang Steglich in 1978. It is an adaptation of an older method for the formation of
amide
In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it i ...
s by means of DCC (dicyclohexylcarbodiimide) and
1-hydroxybenzotriazole (HOBT).
:
This reaction generally takes place at
room temperature
Colloquially, "room temperature" is a range of air temperatures that most people prefer for indoor settings. It feels comfortable to a person when they are wearing typical indoor clothing. Human comfort can extend beyond this range depending on ...
. A suitable
solvent
A solvent (s) (from the Latin '' solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. Water is a solvent for ...
is
dichloromethane
Dichloromethane (DCM or methylene chloride, methylene bichloride) is an organochlorine compound with the formula . This colorless, volatile liquid with a chloroform-like, sweet odour is widely used as a solvent. Although it is not miscible wit ...
. 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
Urea, also known as carbamide, is an organic compound with chemical formula . This amide has two amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest amide of carbamic acid.
Urea serves an important ...
compound
dicyclohexylurea
Dicyclohexylurea is an organic compound, specifically, a urea. It is the byproduct of the reaction of dicyclohexylcarbodiimide with amines or alcohols. It may be prepared by the reaction of cyclohexylamine
Cyclohexylamine is an organic compound, ...
(DCU).
Reaction mechanism
The
reaction mechanism
In chemistry, a reaction mechanism is the step by step sequence of elementary reactions by which overall chemical change occurs.
A chemical mechanism is a theoretical conjecture that tries to describe in detail what takes place at each stage o ...
is described as follows:
With
amine
In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent ...
s, the reaction proceeds without problems to the corresponding
amide
In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it i ...
s 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:
References
Further reading
*
* J. Otera: ''Esterification''. 1. Auflage, Wiley-VCH, Weinheim, 2003, {{ISBN, 3-527-30490-8
External links
Mechanism for the Steglich esterification
Name reactions
Esterification reactions