amidáció

Amidáció (amidation) is a chemical reaction that forms an amide bond by combining a carboxylic acid derivative with an amine or ammonia. The typical product is an amide of the form R-CO-NR'R'', with water or another leaving group removed in the process. In practice, amidation usually requires activation of the carboxyl group, which can be achieved by converting the carboxylic acid into a more reactive derivative such as an acid chloride, an acid anhydride, or an activated ester, or by using coupling reagents (for example DCC, EDC, DIC) often in combination with additives like HOBt or HOAt. Direct condensation of a carboxylic acid with an amine is possible under dehydrating conditions or at elevated temperatures, but activation strategies are commonly used to improve yields and selectivity.

Mechanism and scope: amidation proceeds via nucleophilic attack of the amine on the carbonyl carbon of the activated carboxyl derivative, forming a tetrahedral intermediate that collapses to yield the amide while expelling a leaving group. The method chosen depends on substrate sensitivity, desired selectivity, and the presence of other functional groups. Direct amidation can be challenging for sterically hindered amines or less reactive carboxylic acids, whereas activated esters, acid chlorides, or coupling reagents offer broader scope. Enzymatic methods, including amidases and proteases, enable biocatalytic amidation under mild conditions, particularly for peptide synthesis.

Applications: amidation is central to peptide and protein chemistry, pharmaceutical synthesis, and the production of polyamides such as nylons. It is also used in small-molecule drug development and material science for forming amide linkages in complex architectures.

Limitations: the reaction is often driven by removing water or using activating agents, which can generate byproducts or require careful purification. Racemization can occur at chiral centers during activation, and functional group compatibility must be considered.