Pechmann condensation

The Pechmann condensation is a synthesis of coumarins, starting from a phenol and a carboxylic acid or ester containing a β-carbonyl group [J. A. Joule, K. Mills "Heterocyclic Chemistry", 4th edition, Blackwell Science, Oxford, UK, 2000.] . The condensation is performed under acidic conditions. The mechanism involves an esterification/transesterification followed by attack of the activated carbonyl ortho to the oxygen to generate the new ring. The final step is a dehydration, as seen following an aldol condensation. It was discovered by the German chemist Hans von Pechmann [cite journal
author= H. v. Pechmann
title = Neue Bildungsweise der Cumarine. Synthese des Daphnetins
journal = Berichte der deutschen chemischen Gesellschaft
year = 1884
volume = 17
issue = 1
pages = 929–936
doi = 10.1002/cber.188401701248] .

With simple phenols, the conditions are harsh, although yields may still be good [Eugene H. Woodruff , "Organic Syntheses, Coll. Vol. 3", p.581. [http://www.orgsyn.org/orgsyn/prep.asp?prep=cv3p0581 Available online] .] .

With highly activated phenols such as resorcinol, the reaction can be performed under much milder conditions. This provides a useful route to umbelliferone derivatives:

For coumarins unsubstituted at the 4-position, the method requires the use of formylacetic acid or ester. These are unstable and not commercially available, but the acid may be produced "in situ" from malic acid and sulfuric acid above 100°C. As soon as it forms, the formylacetic acid performs the Pechmann condensation. In the example shown, umbelliferone itself is produced, albeit in low yield:

See also

*Aldol condensation
*Perkin reaction

References