Organic Syntheses, CV 4, 478
[Method 1]
Submitted by T. S. Wheeler
1
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
Büchner 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
81–87° is
22–23 g. It is recrystallized from
25 ml. of methanol, and the
o-benzoyloxyacetophenone is obtained as white crystals; yield
19–20 g. (
79–83%); m.p.
87–88°.
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.
90–93°. The crude material is dissolved in
400 ml. of hot ligroin (b.p.
60–70°). 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
8–9 g. (
43–48%); m.p.
96–97°.
[Method 2]
1. Procedure
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
14.5–15 g. (
94–97%); m.p.
95–97°. The over-all yield of
flavone based on
o-hydroxyacetophenone is
59–68%. The product may be recrystallized from
ligroin as in Method 1.
2. Notes
2.
Glycerol is twice distilled under reduced pressure and used immediately in the reaction.
4. The mixture usually becomes so thick and pasty that hand stirring is necessary.
3. Discussion
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' method
6 is satisfactory, but the yield of
o-hydroxydibenzoylmethane is variable.
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