Checked by William S. Johnson, Donald W. Stoutamire, and A. L. Wilds.
1. Procedure
A.
o-Methylbenzyl acetate. A solution of
29.8 g. (0.20 mole) of 2-methylbenzyldimethylamine (p.585) and
32.7 g. (0.30 mole) of ethyl bromide in
40 ml. of absolute ethanol is placed in a
500-ml. round-bottomed flask fitted with a reflux condenser capped with a calcium chloride drying tube. The solution is heated under reflux on the
steam bath for 1 hour; then an additional
10.8 g. (0.10 mole) of ethyl bromide is added and the heating continued for an additional 3 hours. The solvent and residual
ethyl bromide are removed to reduced pressure (
water aspirator) while the flask is heated in a
water bath kept at about 60° (Note
1). The oily residue is treated with about
300 ml. of absolute ether, and on scratching crystallization is induced. The product is collected on a
Büchner funnel, washed with two
50-ml. portions of anhydrous ether, and dried in a
vacuum desiccator. The yield of colorless
2-methylbenzylethyldimethylammonium bromide is
47.5–49.0 g. (
92–95%) (Note
2). It is hygroscopic and should therefore not be exposed to moist air.
In a
500-ml. round-bottomed flask, fitted with a reflux condenser capped with a calcium chloride drying tube, are placed
38.7 g. (0.15 mole) of the quaternary ammonium bromide (Note
3) described above,
24.6 g. (0.3 mole) of fused sodium acetate, and
100 ml. of glacial acetic acid. The mixture is boiled under reflux for 24 hours (Note
4) and then allowed to cool. It is transferred to a
large beaker (Note
5), 250 ml. of water is added, and the acid is partially neutralized by the addition of
84 g. of solid sodium bicarbonate. The mixture is extracted with three
75-ml. portions of ether, and the combined
ether solutions are washed with two or more
50-ml. portions of saturated sodium bicarbonate solution until all the
acetic acid has been removed. The
ether layer is then washed with
50 ml. of saturated sodium chloride solution and dried over anhydrous
sodium sulfate. The
ether is removed by distillation, and the residue is distilled under reduced pressure. The yield of colorless liquid acetate, b.p.
119–121°/15 mm. or
129–131°/31 mm., is
21.6–22.4 g. (
88–91%),
nD25 1.5041–1.5045 (Note
6).
B.
o-Methylbenzyl alcohol. A solution of
5 g. (0.12 mole) of sodium hydroxide in 50 ml. of water is added to a solution of
16.4 g. (0.1 mole) of 2-methylbenzyl acetate (prepared as described above, part A) in
50 ml. of methanol contained in a
250-ml. round-bottomed flask fitted with a reflux condenser. The mixture is boiled under reflux for 2 hours, cooled, diluted with 50 ml. of water, and extracted with three
75-ml. portions of ether. The combined
ether solutions are washed with 50 ml. of water and
50 ml. of saturated sodium chloride solution and dried over
anhydrous sodium sulfate. The solvent is removed by distillation, finally at reduced pressure to remove the last traces of
methyl alcohol, and the residue is dissolved in
50 ml. of boiling 30–60° petroleum ether. The colorless crystals obtained on cooling, finally in the
ice bath, are collected by suction filtration, washed with a few milliliters of cold petroleum ether, and air-dried. Concentration of the mother liquors to 6–7 ml. and cooling gives an additional crop. The total yield of product melting between
33–34° and 35–36° is
11.6–11.8 g. (
95–97%) (Note
7).
2. Notes
1. A
capillary ebullition tube is used to prevent bumping.
3. The ethobromides are preferable to methiodides in this reaction, because the former salts are more soluble in glacial
acetic acid and do not liberate halogen as do the iodides.
4. The
sodium acetate dissolves as the mixture reaches reflux temperature, but a small amount of solid (perhaps
sodium bromide) remains undissolved throughout the heating.
5. Considerable foaming may occur during the neutralization, and material may be lost if the process is carried out in a
small narrow-mouthed vessel.
6. The submitters have used the same procedure for the preparation of
2,3-dimethylbenzyl acetate from the corresponding quaternary salt (Note
2). The yield of material b.p.
127–129°/9 mm. was
94%.
3. Discussion
The vicinal methylbenzyl alcohols have been prepared in general by the abnormal reaction of the appropriately substituted Grignard reagent with
formaldehyde.
2 The present method is preferred over the former because it yields purer products than the Grignard approach.
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