The Pechmann condensation is a synthesis of coumarins, starting from a phenol and a carboxylic acid or ester containing a β-carbonyl group.[1] 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 GermanchemistHans von Pechmann[2] .
To synthesize coumarin derivatives, β-ketoesters can be condensed with phenols under acidic conditions.[3] In this case, a transesterification occurs first with the formation of the phenol ester. This is then followed by ring closure, similar to Friedel-Crafts alkylation.
Examplesedit
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:
The Pechmann condensation as applied to 7-hydroxy-4-methylcoumarin
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:
The Pechmann condensation as applied to umbelliferone
Mechanistic studiesedit
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 cyclizationedit
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.
^J. A. Joule, K. Mills Heterocyclic Chemistry, 4th edition, Blackwell Science, Oxford, UK, 2000.
^Eugene H. Woodruff , Organic Syntheses, Coll. Vol. 3, p.581. Available online 2011-05-14 at the Wayback Machine.
^Daru, János; Stirling, András (4 November 2011). "Mechanism of the Pechmann Reaction: A Theoretical Study". The Journal of Organic Chemistry. 76 (21): 8749–8755. doi:10.1021/jo201439u. PMID 21932799.
^Name reactions: a collection of detailed reaction mechanisms, Jie Jack Li.
December 07, 2023
pechmann, condensation, synthesis, coumarins, starting, from, phenol, carboxylic, acid, ester, containing, carbonyl, group, condensation, performed, under, acidic, conditions, mechanism, involves, esterification, transesterification, followed, attack, activate. The Pechmann condensation is a synthesis of coumarins starting from a phenol and a carboxylic acid or ester containing a b carbonyl group 1 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 2 Pechmann condensationNamed after Hans von PechmannReaction type Ring forming reactionReactionPhenol b keto carboxylic acid or b keto ester Coumarin s ConditionsTemperature VariableCatalyst Strong acids AlCl3 CH4SO3 H2SO4IdentifiersOrganic Chemistry Portal pechmann condensation Contents 1 Mechanism 2 Examples 3 Mechanistic studies 4 Simonis chromone cyclization 5 See also 6 ReferencesMechanism editTo synthesize coumarin derivatives b ketoesters can be condensed with phenols under acidic conditions 3 In this case a transesterification occurs first with the formation of the phenol ester This is then followed by ring closure similar to Friedel Crafts alkylation nbsp Examples editWith simple phenols the conditions are harsh although yields may still be good 4 nbsp With highly activated phenols such as resorcinol the reaction can be performed under much milder conditions This provides a useful route to umbelliferone derivatives nbsp The Pechmann condensation as applied to 7 hydroxy 4 methylcoumarinFor 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 nbsp The Pechmann condensation as applied to umbelliferoneMechanistic studies editThe 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 editIn 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 nbsp See also editAldol condensation Kostanecki acylation Perkin reactionReferences edit J A Joule K Mills Heterocyclic Chemistry 4th edition Blackwell Science Oxford UK 2000 H v Pechmann 1884 Neue Bildungsweise der Cumarine Synthese des Daphnetins Berichte der deutschen chemischen Gesellschaft 17 1 929 936 doi 10 1002 cber 188401701248 J A Joule K Mills Heterocyclic Chemistry 4th edition Blackwell Science Oxford UK 2000 Eugene H Woodruff Organic Syntheses Coll Vol 3 p 581 Available online Archived 2011 05 14 at the Wayback Machine Daru Janos Stirling Andras 4 November 2011 Mechanism of the Pechmann Reaction A Theoretical Study The Journal of Organic Chemistry 76 21 8749 8755 doi 10 1021 jo201439u PMID 21932799 E Petschek H Simonis Ber 46 2014 1913 Name reactions a collection of detailed reaction mechanisms Jie Jack Li Retrieved from https en wikipedia org w index php title Pechmann condensation amp oldid 1150748801, wikipedia, wiki, book, books, library,
