Steglich esterification

The Steglich esterification is a name reaction in organic chemistry . It is an esterification method and was first described in 1978 by Wolfgang Steglich (* 1933). With this process, sterically demanding alcohols can be esterified with carboxylic acids.

Overview reaction

Under the influence of dicyclohexyl carbodiimide (DCC) and 4-dimethylaminopyridine (DMAP) are secondary and tertiary alcohols esterified. Here R ¹ , R ² , R ^{3 are} alkyl or aryl radicals and R ⁴ is an alkyl, aryl radical or hydrogen atom.

mechanism

Side reaction esterification using the DCC method: acyl migration in the case of acylisourea

The Steglich esterification is an adaptation of the method using DCC and 1-hydroxybenzotriazole (HOBT), which has been known for a long time for the formation of carboxamides . However, undesirable side reactions can occur when carboxylic esters are prepared using the DCC method. Due to a [1,3] rearrangement at the O - acylisourea , this reacts irreversibly to form N -acylisourea. Acetyl transfer agents such as DMAP prevent this acyl migration . The so-called Steglich catalyst DMAP accelerates the DCC-activated esterification in such a way that the formation of by-products does not occur and sterically demanding esters are formed in good yields at room temperature.

For the sake of clarity, the following reaction mechanism with a primary alcohol is shown.

The carboxy group of the carboxylic acid 1 adds to a C = N double bond of the DCC ( N , N '-dicyclohexylcarbodiimide) ( 2 ), the O - acylisourea 5 being formed. As an intermediate step, the carboxylate anion 3 and the compound 4 are formed by protonation of the DCC . The use of DCC accelerates the reaction, since the reactivity of the O -acylisourea is higher than that of the carboxylic acid.

In order to increase the yield, DMAP (4-dimethylaminopyridine) ( 6 ) is used. DMAP is more nucleophilic than alcohol and reacts with the O -acylisourea 5 to form a reactive N -acylpyridinium ion 7 :

The alcohol then reacts with the reactive intermediate, the N -acylpyridinium ion 7 . In an equilibrium reaction, a proton transfer takes place:

In the last step, the deprotonated N , N '-dicyclohexylurea attacks the proton of compound 8 , the corresponding ester 9 being formed and 6 being split off. The water released during esterification is absorbed by the DCC with the formation of N , N ′ -dicyclohexylurea (DCU):

(DCU, "U" stands for the Latin term "Urea" for urea)

Individual evidence

↑ ^a ^b B. Neises, W. Steglich: Simple process for the esterification of carboxylic acids. In: Angewandte Chemie . Volume 90, 1978, pp. 556-557.
↑ JCn Sheehan, GP Hess: A New Method of Forming Peptide Bonds. In: J. Am. Chem. Soc. 77, 1955, pp. 1067-1068.
↑ W. König, R. Geiger: A new method for the synthesis of peptides: Activation of the carboxy group with dicyclohexylcarbodiimide with the addition of 1-hydroxy-benzotriazoles. In: Chemical Reports . 103, 1970, pp. 788-798.
^ ^A ^b Zerong Wang: Comprehensive Organic Name Reactions and Reagents . Set of 3 volumes. John Wiley & Sons, Hoboken, NJ 2009, ISBN 978-0-471-70450-8 , pp. 2651-2655 .

literature

J. Otera: Esterification. 1st edition. Wiley-VCH, Weinheim 2003, ISBN 3-527-30490-8 .

Web links

Steglich esterification mechanism

[Steglich-1] B. Neises, W. Steglich: Simple process for the esterification of carboxylic acids. In: Angewandte Chemie . Volume 90, 1978, pp. 556-557.

[2] JCn Sheehan, GP Hess: A New Method of Forming Peptide Bonds. In: J. Am. Chem. Soc. 77, 1955, pp. 1067-1068.

[3] W. König, R. Geiger: A new method for the synthesis of peptides: Activation of the carboxy group with dicyclohexylcarbodiimide with the addition of 1-hydroxy-benzotriazoles. In: Chemical Reports . 103, 1970, pp. 788-798.

[Wang-4] A ^b Zerong Wang: Comprehensive Organic Name Reactions and Reagents . Set of 3 volumes. John Wiley & Sons, Hoboken, NJ 2009, ISBN 978-0-471-70450-8 , pp. 2651-2655 .