Algar-Flynn-Oyamada Reaction

The conversion of 2 -hydroxychalcones to 2-aryl-3-hydroxy-4f/-lbenzopyran-4-ones (flavonols) by alkaline hydrogen peroxide oxidation is known as the Algar-Flynn-Oyamada (AFO) reaction or AFO oxidation.  

In 1934 the transformation of 2 -hydroxychalcones to flavonols in the presence of hydrogen peroxide and sodium hydroxide was reported simultaneously by Algar and Flynn in Ireland and Oyamada in Japan However, many reports following the original disclosures showed that the Algar-Flynn-Oyamada reaction could lead to several products including aurones 4, dihydroflavonols 5, 2-benzyl-2-hydroxydihydrobenzofuran-3-ones 6, and 2-arylbenzofuran-3-carboxylic acids 

Despite the formation of several products, the AFO reaction has remained a popular method for the synthesis of flavonols. 

It is also hypothesized that formation of 2-benzyl-2-hydroxydihydrobenzofuran-3-ones 6 and 2-arylbenzofuran-3-carboxylic acids 7 are derived from an intramolecular attack of the phenoxide at the P-position. Despite the complex mechanism and multiple products, general trends have emerged through experimental results. If the chalcone lacks a 6 -methoxy group but has a hydroxyl group at the C2 or C4 positions, flavonols are favored. However, if the 6 -methoxy group is present and no hydroxyl substituent is present at C2 or C4 aurones and flavonols are formed. Others have also shown that pH and temperature influence the product distribution. 

The AFO reaction has seen very few variations since it was first reported in 1934. However, the most significant modification was reported in 1958 by Ozawa and further elaborated by Smith and others. Prior to this modification the intermediate chalcones were purified and then subjected to hydrogen peroxide in a basic medium. With the modification, the chalcone was generated in situ, from an aldehyde and a hydroxyacetophenone, and then allowed to react with aqueous hydrogen peroxide in the presence of sodium hydroxide to deliver the flavonol. Smith and coworkers conducted a limited study to examine the scope and limitations of this modification.Flavonols were delivered in 51-67% however, no flavonols were isolated with highly reactive aldehydes such as p-nitrobenzaldehyde and when 2-hydroxy-4-methoxyacetophenone was used. 

Stuessy, T. F. Flavonoids of the Sunflower Family (Asteraceae) Springer-Verlag New York, 2001. (Review). 

Name Reactions, 4th ed., DOI 10.1007/978-3-642-01053-8 3, Springer-Verlag Berlin Heidelberg 2009 

Wollenweber, E. In The Flavonoids Advances in Research, Harbome, J. B. Mabry, T. J., Eds Chapman and Hall New York, 1982 pp 189-259. (Review). 

Name Reactions A Collection of Detailed Mechanisms and Synthetic Applications, DOI 10.1007/978-3-319-03979-4 3, Springer International Publishing Switzerland 2014 

Exanqjle 3, The side reaction dominated to give the aurone derivative  

Irish Acad 1934, B42, 1-8. Algar and Flynn were 

---

Aminofiavones are also available from chalcones derived from 5-acetamino-2-hydroxyacetophenone (57JOC304). Oxidation by selenium dioxide leads to 6-acetaminoflavones which may be deacetylated to the 6-amino compound, whilst alkaline hydrogen peroxide affords the corresponding flavonols (461) in a typical Algar-Flynn-Oyamada reaction (64CB610). 

Algar-Flynn-Oyamada reaction. Alkaline hydrogen peroxide oxidation of o-hydroxyphenyl styryl ketones (chalcones) to flavonols via the intermediate dihydroflavonols. 

The Algar-Flynn-Oyamada reaction is a convenient and efficient ntethod of converting a chalcone into a 3 hydroxyflavone [2392] but chalcones which contain a 6 -substituent (R H) give benzofuran-3-ones (coumarones) instead [2261]. A dehydrogenative high-yielding cyclization of a chalcone may be effected by heating with selenium dioxide in isopentyl alcohol [2521]. 

Other references related to the Algar-Flynn-Oyamada reaction are cited in the literature. 

Limberakis, C. Algar-Flynn-Oyamada Reaction. In Name Reactions in Heterocyclic Chemistry, Li, J. J., Corey, E. J., Eds. Wiley Sons Hoboken, NJ, 2005, pp 496-503. (Review). 

Algar-Flynn-Oyamada Reaction Allan-Robinson Reaction Allvlic Rearrangements Aluminum Alkoxide Reduction... 

---