Organic Syntheses, CV 5, 718
Submitted by Marion L. Miles, Thomas M. Harris, and Charles R. Hauser
1.
Checked by Victor Nelson, Wayland E. Noland, and William E. Parham.
1. Procedure
Caution!
Sodium hydride causes severe burns if brought into contact with the skin and, in the dry state, is pyrophoric. Since
hydrogen is evolved during the course of the reaction, the necessary precautions against fire and explosion should be taken.
A
1-l. three-necked flask is fitted with a sealed mechanical stirrer, an addition funnel with a pressure-equalizing side arm, and a reflux condenser with a gas take-off at the upper end. The gas take-off is connected by means of rubber tubing to one arm of a
glass Y-tube. The other arm of the Y-tube is connected to a source of dry
nitrogen gas. The bottom of the Y-tube is immersed just beneath the surface of a little
1,2-dimethoxyethane (monoglyme) contained in a
small beaker.
The flask is swept with a stream of dry
nitrogen.
Monoglyme (100 ml.) (Note
1) and
sodium hydride (6 g., 0.25 mole) (Note
2) are placed in the flask. A solution of
8.1 g. (0.050 mole) of benzoylacetone (Note
3) and
12.5 g. (0.075 mole) of methyl anisate (Note
4) in
100 ml. of monoglyme is placed in the addition funnel. The funnel is stoppered, and the
nitrogen flow rate is adjusted so that approximately 10 bubbles per minute are emitted from the bottom of the Y-tube. The
sodium hydride slurry is stirred and heated on the
steam bath. When reflux is obtained, the solution of
benzoylacetone and
methyl anisate is added slowly so that
hydrogen evolution is maintained at a controllable rate. The reaction mixture is kept at the reflux temperature for 6 hours.
The reaction mixture is then cooled to room temperature, the reflux condenser is replaced with a
distillation condenser equipped with a vacuum take-off, and most of the solvent is removed under reduced pressure (
ca. 100 mm.) until a thick paste is obtained. The mixture is then cooled in an
ice water bath, and
150 ml. of ether is added. Cold water (200 ml.) is placed in the addition funnel, and initially the water is added dropwise
(Caution! Vigorous evolution of hydrogen) until the excess
sodium hydride is destroyed; then the remainder of the water is added more rapidly (Note
5).
The reaction mixture is poured into a
1-l. separatory funnel, and the aqueous layer is removed. The
ether layer is extracted with two 100-ml. portions of water and then with
100 ml. of aqueous 1% sodium hydroxide. The extracts are combined with the original aqueous layer, and the resulting solution is washed once with
100 ml. of fresh ether. Crushed ice (100 g.) is added to the solution, followed by
30 ml. of 12N hydrochloric acid. The product, which precipitates at this point, is removed by filtration, washed with water, and recrystallized from
450 ml. (Note 6) of 95% ethanol. The yield of
1-(p-methoxyphenyl)-5-phenyl-1,3,5-pentanetrione is
11.4–12.8 g. (
77–86%) (Note
7), m.p.
120–121.5°.
2. Notes
2. The submitters used
sodium hydride obtained as a 50% dispersion in mineral oil from Ventron Corp. This material was used as received.
3. The
benzoylacetone was obtained from Eastman Kodak (Eastman grade), m.p.
57–58°.
4.
Eastman Kodak (Eastman grade) methyl anisate was used without further purification.
5. The checkers observed that the thick brown oil, which separates as the water is added, may partially solidify when stored overnight. The solid was melted on a steam bath, placed in the separatory funnel, and processed with the rest of the reaction mixture as described.
6. The checkers used
480 ml. of 95% ethanol.
7. The checkers found that the product retained as much as
2 g. of ethanol after 20 minutes of air drying. The product was dried to constant weight.
3. Discussion
4. Merits of the Preparation
This procedure appears to be fairly general for the aroylation of β-diketones to give 1,3,5-triketones. Using this method, the submitters
2 have aroylated
benzoylacetone with
methyl benzoate (87%),
methyl p-chlorobenzoate (78%), and
ethyl nicotinate (69%). Also,
acetylacetone has been monobenzoylated with
methyl benzoate to form
1-phenyl-1,3,5-hexanetrione in
75% yield or dibenzoylated with the same ester to form
1,7-diphenyl-1,3,5,7-heptanetetraone in
56% yield.
6 Symmetrical 1,5-diaryl-1,3,5-pentanetriones can be conveniently prepared by a similar procedure
2 from
acetone and two equivalents of the appropriate aromatic ester; for example,
1,5-diphenyl-1,3,5-pentanetrione and
1,5-di(p-methoxyphenyl)-1,3,5-pentanetrione are formed in yields of
82% and
77%, respectively.
1,3,5-Triketones are useful intermediates in the preparation of 4-pyrones, 4-pyridones,
3,4 and other cyclic products.
This preparation is referenced from:
Appendix
Compounds Referenced (Chemical Abstracts Registry Number)
1,2-dimethoxyethane (monoglyme)
Monoglyme
ethanol (64-17-5)
hydrochloric acid (7647-01-0)
ammonia (7664-41-7)
ether (60-29-7)
hydrogen (1333-74-0)
sodium hydroxide (1310-73-2)
nitrogen (7727-37-9)
acetone (67-64-1)
sodium (13966-32-0)
methyl benzoate (93-58-3)
Acetylacetone (123-54-6)
benzoylacetone (93-91-4)
sodium hydride (7646-69-7)
calcium hydride (7789-78-8)
1,2-dimethoxyethane (110-71-4)
methyl anisate (121-98-2)
ethyl nicotinate (614-18-6)
1-phenyl-1,3,5-hexanetrione
1,7-diphenyl-1,3,5,7-heptanetetraone
1,5-diphenyl-1,3,5-pentanetrione (1467-40-9)
1-(p-Methoxyphenyl)-5-phenyl-1,3,5-pentanetrione,
1,3,5-Pentanetrione, 1-(p-methoxyphenyl)-5-phenyl- (1678-17-7)
2-(p-Methoxyphenyl)-6-phenyl-4-pyrone (14116-43-9)
methyl p-chlorobenzoate (1126-46-1)
1,5-di(p-methoxyphenyl)-1,3,5-pentanetrione
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