Organic Syntheses, CV 6, 859
Submitted by R. N. Mirrington and G. I. Feutrill
1.
Checked by H. Gurien, G. Kaplan, and A. Brossi.
1. Procedure
Caution!
Benzene has been identified as a carcinogen; OSHA has issued emergency standards on its use. All procedures involving
benzene should be carried out in a
well-ventilated hood, and glove protection is required.
A.
Orcinol dimethyl ether. A
1-l., three-necked flask fitted with a
mechanical stirrer, a
condenser, and a
100-ml. dropping funnel is charged with
124 g. (0.984 mole) of anhydrous potassium carbonate,
410 ml. of acetone (Note
1), and
42.6 g. (0.344 mole) of orcinol monohydrate (Note
2). The stirrer is started, and
94.5 g. (70.9 ml., 0.750 mole) of dimethyl sulfate is added from the dropping funnel to the pink mixture over a period of 2 minutes. The mixture warms appreciably and begins to reflux after an additional 5 minutes. When the spontaneous boiling has subsided (15–20 minutes after addition of the
dimethyl sulfate), the stirred mixture is heated gently under reflux for 4 hours longer. The condenser is then arranged for distillation and
200 ml. of acetone is distilled. A
50-ml. portion of concentrated aqueous ammonia is added to the reaction mixture; stirring and heating are continued for 10 minutes. The mixture is diluted with water to a total volume of approximately 750 ml., the layers are separated, and the organic layer is combined with two 150-ml. ethereal extracts of the aqueous layer. The organic phase is washed with 50 ml. of water, twice with
50-ml. portions of 3 N sodium hydroxide solution (Note
3), once with
50 ml. of saturated aqueous sodium chloride, and dried over
magnesium sulfate. After evaporation of the
ether at atmospheric pressure, the residual liquid is distilled under reduced pressure, yielding
42.9–43.7 g. (
94–96%) of
orcinol dimethyl ether, b.p.
133–135° (40 mm.) (Note
4) and (Note
5).
Caution! Because
hydrogen is evolved and large volumes of foul-smelling
ethyl methyl sulfide are liberated, this step should be conducted in a well-ventilated hood.
B.
Orcinol monomethyl ether. A 1-l., three-necked flask equipped with a
magnetic stirrer, a condenser, a dropping funnel, and a
nitrogen inlet is charged with
250 ml. of dry N,N-dimethylformamide (Note
6) and
22 g. (0.55 mole) of sodium hydride (60% oil dispersion). The suspension is stirred under an atmosphere of dry
nitrogen and cooled with an
ice bath while a solution of
31 g. (37 ml., 0.50 mole) of ethanethiol (Note
7) in
150 ml. of dry N,N-dimethylformamide (Note
6) is added slowly from the dropping funnel over a period of 20 minutes. The ice bath is removed and stirring is continued for an additional 10 minutes. A solution of
38.0 g. (36.5 ml., 0.250 mole) of orcinol dimethyl ether in 100 ml. of dry N,N-dimethylformamide (Note
6) is added in one lot, and the mixture is refluxed under an atmosphere of dry
nitrogen for 3 hours (Note
8) and (Note
9). The mixture is cooled, poured into 1.8 l. of cold water, and extracted with two
250-ml. portions of petroleum ether (b.p.
50–70°), which are discarded. The aqueous layer is acidified with
330 ml. of ice-cold 4 N hydrochloric acid and extracted with three
250-ml. portions of ether. The combined ethereal extracts are washed with
100 ml. of saturated aqueous sodium chloride and dried over
magnesium sulfate. After the
ether is distilled at atmospheric pressure, the residual liquid is distilled under reduced pressure, yielding
28–30.5 g. (
81–88%) of
orcinol monomethyl ether, b.p.
89–90° (0.2 mm.) or
156–158° (25 mm.) (Note
10) and (Note
11)
2. Notes
1. Technical
acetone containing about 1% water is quite satisfactory.
2.
British Drug Houses Ltd. reagent grade orcinol monohydrate was used without further purification.
3. If the first washing is colorless, as is usually the case, the second washing is unnecessary. Washing with
sodium hydroxide solution should be continued until the washings are colorless.
5. GC analysis of the product on two columns (silicone gum rubber SE-30 and OV-1) indicated the presence of traces of two other compounds with retention times longer than that of
orcinol dimethyl ether. These impurities, which were most likely
C-methylated materials,
2 totaled less than 0.5% of the product.
8. The mixture may become gelatinous during this time, but stirring is not necessary.
9. A polythene tube leading from the top of the condenser to the back of the hood is advisable, preventing any diffusion of the by-product,
ethyl methyl sulfide, into the laboratory. Alternatively, this by-product may be collected, if desired, by passing the vapors through a cold
trap (dry ice in
acetone).
10. This distillate, which is sufficiently pure for most reactions, solidifies after standing for 4–6 hours. A sample crystallizes from
benzene-petroleum ether as off-white prisms, m.p.
61–62°, and is relatively free of sulfurous odor.
11.
1H NMR (CCl
4): δ 2.19 (s, 3H, C
H3), 3.63 (s, 3H, OC
H3), 6.17 (m, 3H, C
6H3), 6.38 (broad s, 1H, O
H).
3. Discussion
This procedure is characterized by the easy isolation of a high-purity product in excellent yield. The reaction illustrates a general method
6 for the conversion of aryl methyl ethers to the corresponding phenols, and has proved to be of special advantage with acid-sensitive substrates.
6,7
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