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DOI:10.15227/orgsyn.032.0072

Organic Syntheses, Coll. Vol. 4, p.478 (1963); Vol. 32, p.72 (1952).

FLAVONE
[Method 1]

Submitted by T. S. Wheeler1
Checked by R. L. Shriner and Donald A. Scott.

1. Procedure
A. o-Benzoyloxyacetophenone. In a 100-ml. conical flask fitted with a calcium chloride drying tube
are placed 13.6 g. (12 ml., 0.1 mole) of o-hydroxyacetophenone,2 21.1 g. (17.4 ml., 0.15 mole) of
benzoyl chloride, and 20 ml. of pyridine (Note 1). The temperature of the reaction mixture rises
spontaneously, and when no further heat is evolved (about 15 minutes) the mixture is poured with good
stirring into 600 ml. of 3% hydrochloric acid containing 200 g. of crushed ice. The product is collected
on a Bchner funnel and washed with 20 ml. of methanol, then with 20 ml. of water. The product is
sucked as dry as possible and air-dried at room temperature. The yield of dry crude product melting at
8187 is 2223 g. It is recrystallized from 25 ml. of methanol, and the o-benzoyloxyacetophenone is
obtained as white crystals; yield 1920 g. (7983%); m.p. 8788.
B. Flavone. In a 500-ml. round-bottomed three-necked flask, equipped with a mercury-sealed
mechanical stirrer, a thermometer, and an air condenser closed with a calcium chloride drying tube in
the second neck, are placed 20 g. (0.083 mole) of o-benxoyloxyacetophenone and 200 ml. of freshly
distilled anhydrous glycerol (Note 2). A stream of nitrogen, dried by passage through a wash bottle
containing sulfuric acid, is introduced through the third neck. The mixture is heated and maintained at
260 for two hours while being stirred continuously. The contents are cooled below 100 and then
poured into 2 l. of water which is rendered slightly alkaline with aqueous sodium hydroxide. The
mixture is stirred for 15 minutes, cooled, and kept at 0 (in a refrigerator) for 48 hours. The tan-colored
crystals of flavone are collected on a filter and dried at 50. The yield of crude product amounts to about
10 g.; m.p. 9093. The crude material is dissolved in 400 ml. of hot ligroin (b.p. 6070). Repeated
partial evaporation of the solvent in stages, each followed by cooling, gives successive crops of flavone
as white needles. The yield of pure flavone amounts to 89 g. (4348%); m.p. 9697.

[Method 2]

1. Procedure
A. o-Benzoyloxyacetophenone. This is prepared as in Method 1.
B. o-Hydroxydibenzoylmethane. A solution of 20 g. (0.083 mole) of o-benzoyloxyacetophenone in
75 ml. of pyridine (Note 1) is prepared in a 300-ml. beaker and warmed to 50. To the solution is added
7 g. of hot pulverized 85% potassium hydroxide (Note 3), and the mixture is mechanically stirred for 15
minutes, during which time a copious precipitate of the yellow potassium salt of ohydroxydibenzoylmethane forms (Note 4). The mixture is cooled to room temperature and acidified
with 100 ml. of 10% acetic acid. The diketone separates as a light-yellow precipitate which is collected
on a filter and sucked dry (Note 5). The yield of crude o-hydroxydibenzoylmethane is 1617 g. (80
85%); m.p. 117120.
C. Flavone. To a solution of 16.6 g. (0.069 mole) of the crude diketone in 90 ml. of glacial acetic
acid, contained in a 250-ml. conical flask, is added, with shaking, 3.5 ml. of concentrated sulfuric acid.
The mixture is heated under a reflux condenser on a steam bath for 1 hour with occasional shaking and
is then poured onto 500 g. of crushed ice with vigorous stirring. After the ice has melted, the crude
flavone is collected on a filter, washed with water (about 1 l.) until free from acid, and finally dried at
50. The yield of product is 14.515 g. (9497%); m.p. 9597. The over-all yield of flavone based on
o-hydroxyacetophenone is 5968%. The product may be recrystallized from ligroin as in Method 1.

2. Notes
1. Commercial pyridine is dried over solid sodium hydroxide and distilled through a fractionating
column.
2. Glycerol is twice distilled under reduced pressure and used immediately in the reaction.
3. The potassium hydroxide is pulverized rapidly in a mortar previously heated at 100.
4. The mixture usually becomes so thick and pasty that hand stirring is necessary.
5. o-Hydroxydibenzoylmethane can be crystallized from 95% ethanol and forms crystals melting at
120, which give a strong enol reaction with ferric chloride. Crystallization is not necessary here.

3. Discussion
o-Benzoyloxyacetophenone has been prepared by the action of benzoyl chloride on a pyridine
solution of o-hydroxyacetophenone.3 The rearrangement of o-benzoyloxyacetophenone to ohydroxydibenzoylmethane by alkali has been described.4,5 The latter diketone has been made by the
base-catalyzed condensation of ethyl benzoate with o-hydroxyacetophenone.6 The cyclization of ohydroxydibenzoylmethane described in Method 2 is based on the work of Doyle, Gogan, Gowan,
Keane, and Wheeler.5 Cyclization has also been effected by use of glacial acetic acid containing
hydrogen chloride or sodium acetate.4

Other methods of preparing flavone include: the action of ethanolic alkali on 2'-acetoxy-,dibromochalcone;7 Claisen condensation of ethyl o-ethoxybenzoate and acetophenone, and cyclization
of the resulting 1,3-diketone with hydriodic acid;8 and treatment of 3-bromoflavanone with potassium
hydroxide in ethanol.9 Flavone has also been prepared from ethyl phenylpropiolate by condensation
with sodium phenoxide and subsequent cyclization with phosphorus pentachloride in benzene;10 by
fusing o-hydroxyacetophenone with benzoic anhydride and sodium benzoate;11 by the dehydrogenation
of 2'-hydroxychalcone with selenium dioxide;12 by the action of alkali on flavylium chloride;13 by the
acid hydrolysis of 3-benzoyl-4-hydroxycoumarin;14 by the condensation of benzamide with 2hydroxyacetophenone;15 and by heating -morpholino-2-chlorochalcone which cyclizes to 4morpholinoflavylium chloride, and which in turn may be hydrolyzed to flavone.16
Method 1 is a new procedure for the direct production of flavone from o-benzoyloxyacetophenone
and has been successfully applied to the synthesis of other flavones. Method 2, which involves the
Baker-Venkataraman transformation, is recommended because of its high over-all yield and the
reproducibility of the results. Mozingo and Adkins' method6 is satisfactory, but the yield of ohydroxydibenzoylmethane is variable.

References and Notes

1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.

University College, Dublin, Ireland.

Org. Syntheses Coll. Vol. 2, 545 (1943); Org. Syntheses Coll. Vol. 3, 389 (1955).
Freudenberg and Orthner, Ber., 55, 1748 (1922); Baker, J. Chem. Soc., 1933, 1386.
Baker, J. Chem. Soc., 1933, 1386; Bhalla, Mahal, and Venkataraman, J. Chem. Soc., 1935, 868;
Virkar and Wheeler, J. Chem. Soc., 1939, 1681.
Doyle, Gogan, Gowan, Keane, and Wheeler, Sci. Proc. Roy. Dublin Soc., 24, 291 (1948).
Mozingo and Adkins, J. Am. Chem. Soc., 60, 672 (1938).
Feuerstein and Kostanecki, Ber., 31, 1757 (1898).
Kostanecki and Tambor, Ber., 33, 330 (1900).
Kostanecki and Szabranski, Ber., 37, 2634 (1904); Nakagawa and Tsukahima, Nippon Kagaku
Zasshi, 75, 485 (1954) [C. A., 51, 11339 (1957)].
Ruhemann, Ber., 46, 2188 (1913); Bogert and Marcus, J. Am. Chem. Soc., 41, 87 (1919).
Chadha and Venkataraman, J. Chem. Soc., 1933, 1073.
Mahal, Rai, and Venkataraman, J. Chem. Soc., 1935, 866.
Hill and Melhuish, J. Chem. Soc., 1935, 1165.
Veres and Horak, Chem. listy, 48, 1644 (1954), Collection Czechoslov. Chem. Communs., 20,
371 (1955) [C. A., 49, 14756 (1955)].
Gowan, O'Connor, and Wheeler, Chem. & Ind. (London), 1954, 1201.
Southwick and Kirchner, J. Am. Chem. Soc., 79, 689 (1957).

Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
ligroin
o-benxoyloxyacetophenone
ethanol (64-17-5)
sulfuric acid (7664-93-9)

hydrogen chloride,
hydrochloric acid (7647-01-0)
acetic acid (64-19-7)
Benzene (71-43-2)
methanol (67-56-1)
sodium acetate (127-09-3)
sodium hydroxide (1310-73-2)
phosphorus pentachloride (10026-13-8)
glycerol (56-81-5)
nitrogen (7727-37-9)
Acetophenone (98-86-2)
benzoyl chloride (98-88-4)
Benzoic anhydride (93-97-0)
benzamide (55-21-0)
pyridine (110-86-1)
selenium dioxide (7446-08-4)
potassium hydroxide (1310-58-3)
sodium benzoate (532-32-1)
hydriodic acid (10034-85-2)
ferric chloride (7705-08-0)
ethyl benzoate (93-89-0)
sodium phenoxide
ethyl phenylpropiolate (2216-94-6)
2-hydroxyacetophenone (582-24-1)
Flavone (525-82-6)
3-bromoflavanone

flavylium chloride
3-benzoyl-4-hydroxycoumarin
-morpholino-2-chlorochalcone
4-morpholinoflavylium chloride
o-Hydroxyacetophenone (118-93-4)
o-Benzoyloxyacetophenone (4010-33-7)
o-Hydroxydibenzoylmethane (1469-94-9)
ethyl o-ethoxybenzoate
potassium salt of o-hydroxydibenzoylmethane
2'-acetoxy-,-dibromochalcone
2'-hydroxychalcone
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