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Updated: Jan 20, 2026
Carboxylic Acids to Esters: Acid-Catalyzed Fischer Esterification Overview
Formamide catalyzed activation of carboxylic acids - versatile and cost-efficient amidation and esterification
Peter H Huy1, Christelle Mbouhom1
1Saarland University , Institute of Organic Chemistry , P. O. Box 151150 , D-66041 Saarbruecken , Germany . https://www.peterhuylab.de/ ;
Abstract:
A novel, broadly applicable method for amide C-N and ester C-O bond formation is presented based on formylpyrrolidine (FPyr) as a Lewis base catalyst. Herein, trichlorotriazine (TCT), which is the most cost-efficient reagent for OH-group activation, was employed in amounts of ≤40 mol% with respect to the starting material (100 mol%). The new approach is distinguished by excellent cost-efficiency, waste-balance (E-factor down to 3) and scalability (up to >80 g). Moreover, high levels of functional group compatibility, which includes acid-labile acetals and silyl ethers, are demonstrated and even peptide C-N bonds can be formed. In comparison to reported amidation procedures using TCT, yields are considerably improved (for instance from 26 to 91%) and esterification is facilitated for the first time in synthetically useful yields. These significant enhancements are rationalized by activation by means of acid chlorides instead of less electrophilic acid anhydride intermediates.
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01:20Carboxylic Acids to Esters: Acid-Catalyzed (Fischer) Esterification Overview
01:13Carboxylic Acids to Esters: Acid-Catalyzed (Fischer) Esterification Mechanism
01:28Amides to Carboxylic Acids: Hydrolysis
Acid-catalyzed hydrolysis:
Hydrolysis of amides under acidic conditions yields carboxylic acids. Since the reaction occurs slowly, hydrolysis requires the conditions of heat.
The mechanism begins with the protonation of the carbonyl oxygen by the acid catalyst. The protonation makes the amide carbonyl carbon more...
01:13Esters to Carboxylic Acids: Acid-Catalyzed Hydrolysis
During hydrolysis, the ester is first activated towards nucleophilic attack through the protonation of the carboxyl oxygen atom by the acid catalyst. The protonation makes the ester carbonyl carbon more electrophilic. In the next step, water acts as a nucleophile and adds to the...
01:11Nomenclature of Carboxylic Acid Derivatives: Amides and Nitriles
The IUPAC and common names of amides are derived from the parent carboxylic acid, by replacing the suffix “oic acid” and “ic acid,” respectively, with “amide.” In the following example, the IUPAC name ethanamide is derived from ethanoic acid, and the common name, acetamide, is obtained from acetic acid.
03:48Esterification
The structure of an ester is a carbonyl with an alkyl or aryl group (R) on one side, and an oxygen bound to another alkyl or aryl group (R’) on the other side, represented by the general formula: RCOOR’. Esters can be commonly derived by an esterification reaction between a carboxylic acid and an alcohol. The hydroxyl group of the carboxylic acid is replaced by an alkyl or aryl group. Simple esters, which have low molecular weight and small R and R’ functional groups,...