Org. Synth. 1929, 9, 12
DOI: 10.15227/orgsyn.009.0012
ANISOLE
Submitted by G. S. Hiers and F. D. Hager.
Checked by Henry Gilman, S. A. Harris, and G. F. Wright.
1. Procedure
In a 5-l., three-necked, round-bottomed flask fitted with an efficient stirrer, separatory funnel, and reflux condenser is placed a mixture of 235 g. (2.5 moles) of phenol and 100 g. (2.5 moles) of sodium hydroxide (Note 1) in 1 l. of water. The mixture is cooled, with stirring, in an ice-salt bath to below 10°. There is then added through the separatory funnel, with stirring, 315 g. (235 cc., 2.5 moles) of dimethyl sulfate (Note 2). This addition requires about one hour, and the cooling bath is not removed until the addition is complete. The mixture is then heated on a water bath for one-half hour. At the end of this time there is added through the separatory funnel a mixture of 235 g. (2.5 moles) of phenol and 100 g. (2.5 moles) of sodium hydroxide in 1 l. of water. This addition requires about fifteen minutes. The mixture is then refluxed vigorously over a free flame for fifteen hours (Note 3).
The mixture is cooled and the
anisole layer is separated. The aqueous portion is extracted with about
200 cc. of benzene (Note 4). The combined
anisole-benzene portion is washed once with water, dried over
calcium chloride and distilled from a
modified Claisen flask (p. 130). The portion boiling at 100–153° is refractionated. The main fraction distils at
153–154°/748 mm. The yield is
388–405 g. (
72–75 per cent of the theoretical amount)
(Note 5) and
(Note 6).
2. Notes
1.
The
sodium hydroxide was a high quality technical grade.
2.
Dimethyl sulfate is toxic, but with due care to avoid spattering of the liquid and inhaling of the vapor the operation may be carried out without the use of a
hood.
Ammonia is a specific antidote for
dimethyl sulfate and should be kept at hand to destroy any of the ester accidentally spilled.
A good technical grade of dimethyl sulfate was used.
3.
When the period of refluxing is shorter, the yield is materially decreased. The first methyl group reacts easily but the second only with considerable difficulty. A longer period of refluxing does not give much larger yields. As the
sodium sulfate concentration increases, the
dimethyl sulfate hydrolyzes less readily.
It is recommended that the addition of dimethyl sulfate is best effected at the lowest temperature where reaction takes place readily. With phenol this is 25–35°. For the second methyl group, the mixture is not refluxed but the anisole is boiled out, during which time the reaction completes itself (W. W. Hartman, private communication).
4.
A separate fractional distillation of this
benzene extract yields
9–18 g. of
anisole. The major part of the
anisole contained in the aqueous layer may be recovered by steam distillation instead of a
benzene extraction. Neither method of recovery is wholly satisfactory.
5.
When only one-half the amount of
phenol is used, the yield is
85–92 per cent but with fairly inexpensive
phenol it is more profitable to operate in such a manner that both methyl groups of the
dimethyl sulfate are used.
6.
Other methyl ethers may be prepared by a similar procedure.
Methyl β-naphthyl ether is obtained in a
65–73 per cent yield by adding the
dimethyl sulfate over a period of thirty minutes to equivalent quantities of
β-naphthol and
sodium hydroxide kept cool by an ice-water bath, then heating for one hour at 75–78°, and, finally, crystallizing from
benzene to obtain the pure
methyl ether which melts at
71°.
3. Discussion
Anisole can be prepared from
phenol or its salts by the use of the following methylating agents:
methyl chloride;
1 sodium methyl sulfate;
2 methyl alcohol in the presence of
thorium oxide;
3 methyl alcohol and
β-naphthalenesulfonic acid4 or
potassium hydrogen sulfate5 or
boron fluoride;
6 dimethyl sulfate;
7 and
methyl ether and
boron fluoride.
8
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
anisole-benzene
calcium chloride (10043-52-4)
ammonia (7664-41-7)
Benzene (71-43-2)
methyl alcohol (67-56-1)
sodium hydroxide (1310-73-2)
phenol (108-95-2)
sodium sulfate (7757-82-6)
β-naphthol (135-19-3)
Anisole (100-66-3)
dimethyl sulfate (77-78-1)
Methyl β-naphthyl ether (93-04-9)
methyl ether (115-10-6)
methyl chloride (74-87-3)
sodium methyl sulfate (512-42-5)
thorium oxide
β-naphthalenesulfonic acid (120-18-3)
potassium hydrogen sulfate (7646-93-7)
boron fluoride (7637-07-2)
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