Kostanecki acylation

The Kostanecki acylation is a method used in organic synthesis to form chromones ^[1] or coumarins ^[2] by acylation of O-hydroxyaryl ketones with aliphatic acid anhydrides, followed by cyclization. ^[3] If benzoic anhydride (or benzoyl chloride) is used, a particular type of chromone called a flavone is obtained. It was named after Polish chemist Stanisław Kostanecki.

Mechanism

The mechanism consists of three well-differentiated reactions: ^{[4] [5]}

1. Phenol O-acylation with formation of a tetrahedral intermediate
2. Intramolecular aldol condensation to cyclize and to form a hydroxydihydrochromone
3. Elimination of the hydroxyl group to form the chromone (or coumarin)

Examples

• Alvocidib (flavopiridol)
• Dimefline
• Flavoxate

See also

• Allan–Robinson reaction
• Baker–Venkataraman rearrangement

References

1. Gaspar, A.; Matos, M. J. O.; Garrido, J.; Uriarte, E.; Borges, F. (2014). "Chromone: A Valid Scaffold in Medicinal Chemistry" . Chemical Reviews. 114 (9): 4960–92. doi:10.1021/cr400265z. PMID   24555663.
2. Sethna, S. M.; Shah, N. M. (1945). "The Chemistry of Coumarins". Chemical Reviews. 36: 1–62. doi:10.1021/cr60113a001.
3. v. Kostanecki, St.; Różycki, A. (1901). "Ueber eine Bildungsweise von Chromonderivaten". Berichte der Deutschen Chemischen Gesellschaft. 34: 102–109. doi:10.1002/cber.19010340119.
4. Mamedov, V. A.; Kalinin, A. A.; Gubaidullin, A. T.; Litvinov, I. A.; Levin, Ya. A. (2003). "3-Benzoylquinoxalin-2(1H)-one in the Kostanecki-Robinson Reaction. Synthesis and Structure of 2-Oxo-4-phenylpyrano[2,3-b]quinoxaline" . Chemistry of Heterocyclic Compounds. 39 (1): 96–100. doi:10.1023/A:1023028927007. S2CID   98794444.
5. Ellis, G. P. (1977) Chromenes, Chromanones, and Chromones from The Chemistry of Heterocyclic Compounds, Weissberger, A. and Taylor, E. C., eds.; Wiley & Sons: New York, vol. 31, p. 495.