Org. Synth. 1951, 31, 90
DOI: 10.15227/orgsyn.031.0090
QUINACETOPHENONE MONOMETHYL ETHER
[Acetophenone, 2'-hydroxy-5'-methoxy-]
Submitted by G. N. Vyas and N. M. Shah
1.
Checked by William S. Johnson and R. T. Keller.
1. Procedure
In a
1-l. round-bottomed flask fitted with a
reflux condenser and a
calcium chloride guard tube are placed
30.0 g. (0.197 mole) of quinacetophenone2 (Note 1) and
300 ml. of acetone (Note 2). The mixture is warmed on a
steam bath to dissolve the
quinacetophenone. The resulting greenish solution is cooled to room temperature under tap water, and
28 g. (0.20 mole) of anhydrous potassium carbonate is added followed by
42 g. (0.295 mole) of methyl iodide. The mixture is allowed to reflux on a
water bath at 60–70° for about 6 hours
(Note 3).
As much of the acetone as possible is removed by distillation on the water bath (Note 4), and the residual dark-colored liquid is cooled and acidified with 2N sulfuric acid with cooling under the water tap. The resulting mixture is steam-distilled until no oily drops are seen collecting in the condenser. The distillate, which amounts to about 2.5 l., is allowed to stand overnight at room temperature, and the greenish crystals are separated by suction filtration, washed twice with cold water, and air-dried. The yield of quinacetophenone monomethyl ether, m.p. 48–50°, is 18–21 g. (55–64%) (Note 5).
The brown solution remaining in the distilling flask is filtered while hot; on being cooled it gives 6–7 g. of brownish needles of crude quinacetophenone.
2. Notes
1. The
quinacetophenone2 is dried in an
oven at 100–110° for 2–3 hours.
2. The
acetone is dried over anhydrous
potassium carbonate and distilled.
3. The temperature of the water bath should not exceed 70°; otherwise serious bumping may occur.
4. The recovered
acetone may be reused for another methylation.
5. The submitters state that the
dimethyl ether of quinacetophenone is conveniently prepared by the following procedure: In a 1-l. round-bottomed flask fitted with a reflux condenser
60 g. (0.39 mole) of quinacetophenone2 is dissolved in
300 ml. of ethanol by heating. The source of heat is then removed, and to the hot solution are alternately added in five installments with shaking a solution of
sodium hydroxide (40 g. in 100 ml. of water) and
dimethyl sulfate (120 g.). The heat evolved during the reaction makes the solution boil. After the addition is complete (about 20 minutes), the reaction mixture is made alkaline by the further addition of
10 g. of sodium hydroxide in 20 ml. of water and is allowed to reflux on the water bath for 3 hours. The dark mixture is distilled to remove most of the
ethanol, and the residual liquid in the flask is steam-distilled. The distillate, which amounts to about 2.5 l., is cooled in an
ice bath and saturated with
sodium chloride, whereupon a thick oil settles to the bottom. Most of the aqueous layer is decanted, and the remaining oil is extracted with
ether and dried over
calcium chloride. The
ether is removed by distillation, and the residue is fractionated at reduced pressure to give
50–52 g. (
71–74% yield) of material boiling at
152–156°/15 mm., m.p.
20–22°.
3. Discussion
Quinacetophenone monomethyl ether has been prepared by the methylation of
quinacetophenone with
dimethyl sulfate and alkali,
3 by the partial demethylation of
quinacetophenone dimethyl ether;
4 and by the acetylation of
hydroquinone dimethyl ether with
acetyl chloride in the presence of
aluminum chloride.
5 It also has been obtained as a by-product in the preparation of
quinacetophenone dimethyl ether.
6
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
Quinacetophenone monomethyl ether
quinacetophenone
dimethyl ether of quinacetophenone
quinacetophenone dimethyl ether
ethanol (64-17-5)
calcium chloride (10043-52-4)
potassium carbonate (584-08-7)
sulfuric acid (7664-93-9)
ether (60-29-7)
sodium hydroxide (1310-73-2)
acetyl chloride (75-36-5)
sodium chloride (7647-14-5)
dimethyl sulfate (77-78-1)
acetone (67-64-1)
aluminum chloride (3495-54-3)
Methyl iodide (74-88-4)
hydroquinone dimethyl ether (150-78-7)
Acetophenone, 2'-hydroxy-5'-methoxy- (705-15-7)
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