2 -Hydroxychalcones

Phenolic oxygen participates in facile oxypalladation. The intramolecular reaction of 2-hydroxychalcone (105) produces the flavone 106[127]. The ben-zofuran 107 is formed from 2-allyIphenol by exo cyclization with Pd(OAc)2, but benzopyran 108 is obtained by endo cyclization with PdChf S], Normal cyclization takes place to form the furan 109 from 2-(l-phenylethenyl)phe-nol[129]. Benzofuran formation by this method has been utilized in the synthesis of aklavinione (110)[130]. 

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... 

Surprisingly, no marked effect of the substituent R2 on the product ratio was observed whereas in the similar reaction of 2 -hydroxychalcone dibromides a great influence of substituent R2 on the competing reaction pathways was found (ref. 4). Noteworthy, no formation of the azide E (regioisomer of 2) was detected. 

The mechanisms of the cyclisation of 2 -hydroxychalcone derivatives which can lead to flavanones, flavones and aurones have been reviewed <95MI1> and the formation of 3-hydroxy- chromanones and -flavanones from l-(2-hydroxyphenyl)-2-propen-l-ones via the epoxide has been optimised <96JOC5375>. 

Matsushima, R. Suzuki, M. Photochromic properties of 2-hydroxychalcones in solution and polymers. Bull. Chem. Soc. Jpn. 1992, 65, 39-45. 

Matsushima, R. Mizuno, H. Itoh, FI. Photochromic properties of 4-amino-substituted 2-hydroxychalcones. J. Photochem. Photobiol. A Chem. 1995, 89, 251-256. 

Dewar, D. Sutherland, R. G. The photolysis of 2-hydroxychalcone and its possible implication in flavonoid biosynthesis. J. Chem. Soc., Chem. Commun. 1970, 272-273. 

One-pot conversions of 2-hydroxy(acylbenzenes) with anhydrides or acid chlorides to produce coumarins [52-54] and flavones [54-58] under mild liquiddiquid or solidtliquid two-phase conditions via a Baker-Venkataraman type reaction (Scheme 6.19) are catalysed by quaternary ammonium salts. 3-Substituted coumarins are produced from salicylaldehyde and malonodinitrile, or substituted acetonitriles, in high yield (>85%) in a one-pot catalysed sequential aldol-type reaction and cycliza-tion in the absence of an added organic solvent [59]. When 2 -hydroxychalcones are reduced under catalytic two-phase conditions with sodium borohydride, 2,4-cis-flavan-4-ols are produced [60] (see Section 11.3). 

The carbamates formed from 2-hydroxychalcones and alkyl or aryl isocyanates readily cyclize to 3,4-dihydro-l,3-benzoxazin-2-one derivatives <1996CHEC-II(6)301>. When hydroxychalcones 318 with a benzofuran moiety were heated under reflux with phenyl isocyanate in benzene in the presence of a catalytic amount of potassium hydroxide, l,3-benzoxazin-2-one derivatives 320 were formed through the intermediate open-chain carbamates 319 (Scheme 61) <2006JHC437>. 

Gulacsi, K. et al., A short and facile synthetic route to prenylated flavones. Cyclodehydrogenation of prenylated 2 -hydroxychalcones by a hypervalent iodine reagent. Tetrahedron, 54, 13867, 1998. 

Sanicanin Z, Tabakovic I (1986) Electrochemical synthetis of heterocyclic compounds. Part 16. Electrochemical transformation of 2 -hydroxychalcones into flavonoids. Tetrahedr Lett 27 407-408. 

Chrysin shows a similar effect which is much enhanced in tecto-chrysin, owing presumably to methylation of the 7-hydroxyl in techto-chrysin leaving only the keto-associated 5-hydroxyl free in that flavone. Opening the flavone heterocyclic ring to produce 2-hydroxychalcone leaves monophenol activity still partly suppressed because of the remaining carbonyl effect on oxidizability and H-bonding. Since the structure is relatively free to rotate about the ring-to-carbonyl bond, the suppression is less than in tectochrysin. 

The formation of 2-arylbenzofuran-3-carboxylic acids by ring closure of 2-hydroxychalcones (379) [Algar-Flynn (19 34)831a and Oyamada (1935)s31b] can be regarded as involving an intermediate flavanol. Treatment of chalcones (379) with hydrogen peroxide in an alkaline medium normally leads to flavonols (381) or to aurones (382). At the... 

The formation of flavenes by the reduction of 2-hydroxychalcones undoubtedly proceeds via the alcohol and constitutes a simple but useful synthesis (67JCS(C)1933). This route has been developed (68AJC2247) and extended to spiroannelated compounds (99). 

It is of interest to note that the thallium(III) acetate oxidation of a 2 -hydroxychalcone yields a mixture of a flavone, through participation of the 2 -hydroxy group in the cyclization, and a coumaranone, which presumably arises by further oxidation of an intermediate acetal <70JCS(C)119). 

Evidence has been presented that 2-hydroxychalcones are also transformed into flavones on reaction with thallium(III) nitrate (equation 16) (78TL3359). Such a method would be complementary to the isoflavone synthesis if it proves to be of general applicability. 

A wide range of other photocyclizations resulting in the formation of oxygen and sulfur heterocycles have been reported. Only those conversions that are generally applicable and that have some preparative value will be considered in this section. Flavanone (487) is obtained on irradiation of the 2 -hydroxychalcone (488)425 such transformations are best carried out in... 

A mixture of substituted 2 -hydroxychalcone (1 mmol), the corresponding support (5 g) and the additive (5 mg) in a Pyrex tube was subjected to irradiation at 45 W for 20 min in a Maxidigest 350 Prolabo monomode, focused microwave (2.45 GHz) reactor with continuous rotation. The cooled mixture was washed with methylene chloride (2xl0mL) and concentrated in vacuo. The residue was purified by two subsequent column chromatographies (silica gel) by using hexane-acetone (4 1, v/v) and toluene or toluene-ethyl methyl ketone (30 1, v/v) as eluent. 

Another example of an equilibrium involving ring-formation is the cyclization of 2-hydroxychalcones (12) to form chromanones (8 b). The... 

---