Organic Syntheses, Coll. Vol. 6, p.859 (1988); Vol. 53, p.90 (1973).
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.
) 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
), 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.
) of orcinol monomethyl ether
, b.p. 89–90° (0.2 mm.)
or 156–158° (25 mm.) (Note 10)
and (Note 11)
containing about 1% water is quite satisfactory.
British Drug Houses Ltd. reagent grade orcinol monohydrate
was used without further purification.
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.
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
totaled less than 0.5% of the product.
The mixture may become gelatinous during this time, but stirring is not necessary.
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
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.
H NMR (CCl4
): δ 2.19 (s, 3H, CH3
), 3.63 (s, 3H, OCH3
), 6.17 (m, 3H, C6H3
), 6.38 (broad s, 1H, OH
This procedure is characterized by the easy isolation of a high-purity product in excellent yield. The reaction illustrates a general method6
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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