Pechmann condensation

The Pechmann condensation is a synthesis of

Mechanism

To synthesize coumarin derivatives, β-ketoesters can be condensed with phenols under acidic conditions.^[3] In this case, a transesterification reaction occurs first with the formation of the phenol ester. This is then followed by ring closure, similar to Friedel-Crafts alkylation.

Examples

With simple phenols, the conditions are harsh, although yields may still be good.^[4]

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:

Mechanistic studies

The mechanism of the reaction has been studied in details with theoretical treatment.^[5]

The study shown that reaction takes place on oxo-form, and not on enolic-form. Three different oxo-routes have been proposed.

Simonis chromone cyclization

In a variation the reaction of phenols and beta-ketoesters and phosphorus pentoxide yields a chromone. This reaction is called Simonis chromone cyclization.^[6][7] The ketone in the ketoester is activated by P₂O₅ for reaction with the phenol hydroxyl group first, the ester group in it is then activated for electrophilic attack of the arene.

See also

• Aldol condensation
• Kostanecki acylation
• Perkin reaction

References