Organic Syntheses, Coll. Vol. 1, p.58 (1941); Vol. 9, p.12 (1929).
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.
per cent of the theoretical amount) (Note 5)
and (Note 6)
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
is a specific antidote for dimethyl sulfate
and should be kept at hand to destroy any of the ester accidentally spilled.
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).
A separate fractional distillation of this benzene
extract yields 9–18 g.
. 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.
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
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