The Passerini reaction is a nucleophilic addition reaction involving a isocyanide a aldehyde or ketone and a carboxylic acid to form a alpha-acyloxy amide.

This organic reaction was discovered by Mario Passolini in 1921 in Florence Italy. It is one of the oldest multi component reactions and a a good example of a convergent synthesis.

One possible reaction mechanism can be visualised as follows:

In the isocyanide R-NC both the carboxylic acid nucleophile and the carbonyl electrophile add to the carbon atom in two simultaneous nucleophilic addition reactions. The transition state TS# is depicted as a 5-membered ring with partial covalent or double bonding. . The second step of the Passerini reaction is a acyl rearrangement reaction. Support for this reaction mechanism: the reaction proceeds in relatively non-polar solvents (in line with transition state) and the reaction kinetics depend on all three reactants. See also the Ugi reaction.

References

The Passirini Reaction L. Banfi, R.Riva in Organic Reactions vol. 65 L.E. Overman Ed. Wiley 2005 ISNB 0-471-68260-8