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
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.
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.
3. Discussion
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