Organic Syntheses, Coll. Vol. 4, p.110 (1963); Vol. 35, p.11 (1955).
. In a 1-l. three-necked flask (Note 1)
equipped with an efficient mechanical stirrer
, a dropping funnel
, and a gas outlet leading to a hood or trap
are placed 100 g. (0.5 mole) of p-bromoacetophenone (Note 2)
and 300 ml. of glacial acetic acid
. The resulting solution is stirred and cooled to 20°, and a solution of 26 ml. (0.5 mole) of bromine
in 100 ml. of glacial acetic acid
is added dropwise (Note 3)
. Crystals of the mono-α-brominated derivative separate during the addition, which requires about 30 minutes. When the addition is completed, a second solution of 26 ml. (0.5 mole) of bromine
in 100 ml. of glacial acetic acid
is added dropwise. Slight heating may be necessary to keep the reaction proceeding, as indicated by decolorization of the bromine
, but the temperature should be kept as near 20° as possible. During the addition, which requires about 30 minutes, the solid dissolves and crystals of the di-α,α-brominated derivative appear toward the end of the addition. The flask is heated to dissolve the contents, which are transferred, preferably in a hood, to a 1-l. beaker
and cooled rapidly by means of an ice-water bath (Note 4)
. The mixture is filtered with suction (Note 5)
, and the solid is washed with 50% ethanol
until colorless. The air-dried product has a slight pink cast and melts at 89–91°.
The yield is 130–135 g.
) (Note 6)
. A pure, white solid melting at 92–94°
is obtained by recrystallization from ethanol
, but the initial product is sufficiently pure for the next step.
B. p-Bromomandelic acid
. In a Waring-type blender
are placed 89 g. (0.25 mole) of p,α,α-tribromoacetophenone
and 100–150 ml. of cold water. The mixture is stirred for 10–15 minutes, and the contents are transferred to a 1-l. wide-mouthed bottle
. The mixing vessel is rinsed with 150–200 ml. of ice-cold water. The material from the rinse is combined with the mixture in the bottle, and sufficient crushed ice is added to bring the temperature below 10°. One hundred milliliters of a chilled aqueous solution containing 50 g. of sodium hydroxide
is added slowly while the bottle is rotated (Note 7)
. The contents are stored for approximately 4–5 days in a refrigerator (5°) and are shaken occasionally. During this time most of the solid dissolves, but a slight amount remains as a yellow sludge and the liquid assumes a yellow to amber color. The mixture is filtered, and the insoluble material is discarded. An excess of concentrated hydrochloric acid
is added to the filtrate. The entire resulting mixture containing a white solid is extracted with three 200-ml. portions of ether
. The ether
extracts are combined, dried over anhydrous sodium sulfate
, and filtered into a 1-l. flask
. The ether
is carefully removed by distillation using a hot-water bath
to give a yellow oil which solidifies when cooled. The product is recrystallized from 500 ml. of benzene
. The crystals are collected by filtration and washed with benzene
until the filtrate is colorless. The air-dried product (Note 8)
weighs 40–48 g.
based on p,α,α-tribromoacetophenone
), m.p. 117–119° (Note 9)
. A second recrystallization from 500 ml. of benzene
is sometimes necessary.
The use of ground-glass equipment is desirable but not necessary.
The preparation of p-bromoacetophenone
is described in Organic Syntheses.2
The compound is also available from Eastman Kodak Company.
Sometimes the initation of the reaction is slow. The reaction may be started by heating the solution until the bromine
is decolorized (approximately 45°), after which the reaction will proceed normally at 20°.
The checkers found that maximum yields of product were obtained when cooling was carried to the point where crystallization of the solvent commenced. The trace of crystalline solvent quickly melts during the filtering procedure.
These compounds are lachrymatory and should be kept away from the eyes.
An additional quantity of less pure material can be isolated from the glacial acetic acid
mother liquid and alcohol filtrates by evaporation of the solvent. This, after recrystallization from ethanol
, amounts to 15–30 g.
It is important that the reaction mixture be kept cold at this point. The amount of sludge and colored material increases as the temperature increases.
The last traces of benzene
leave very slowly and if present lower the melting point. The product should be thoroughly dried in air or on a clay plate before the melting point is taken.
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