carbonyldiimidazolemediated

Carbonyldiimidazole-mediated refers to reactions that use 1,1'-carbonyldiimidazole (CDI) to activate carboxylic acids or to form carbonyl-derived linkages under mild conditions. In typical processes, CDI reacts with a carboxylic acid to form an O-acyl imidazole intermediate, a highly reactive activated ester that readily undergoes nucleophilic attack by amines, alcohols, or other nucleophiles. This leads to the formation of amide, ester, or carbonate products with imidazole as the leaving group. The approach is widely used to couple carboxyl groups to amines in peptide and amide bond formation, to generate esters from carboxylic acids, and to prepare carbamates or related derivatives.

Applications and scope include peptide synthesis where CDI provides mild activation that reduces racemization; esterification of carboxylic acids; synthesis of carbamates, ureas, and urethanes; and intramolecular cyclizations that form lactams and lactones. CDI-mediated methods are also employed in polymer chemistry to couple monomers bearing carboxyl and hydroxyl groups and in small-molecule synthesis to construct amide or ester linkages with relatively clean byproducts.

Practical considerations include solvent choice (common solvents are DMF, DMSO, or dichloromethane), and typical reaction conditions ranging from room temperature to moderately elevated temperatures. A base or coupling additive (such as DIPEA or triethylamine) may be used to improve efficiency. The primary byproduct is imidazole, which is removable by standard aqueous workup or extraction. CDI is moisture sensitive, so anhydrous conditions are preferred. Compared with some other coupling reagents, CDI often affords cleaner byproducts and milder conditions, though its performance can be limited for highly hindered substrates or very sluggish nucleophiles.