Organic Syntheses, CV 3, 538
Submitted by J. G. Aston, J. D. Newkirk, D. M. Jenkins, and Julian Dorsky.
Checked by R. L. Shriner and C. H. Tilford.
1. Procedure
A.
Dichloroacetophenone. A
3-l. round-bottomed flask is fitted with a
three-holed rubber stopper through which are passed an inlet tube extending to the bottom of the flask, an outlet tube, and a
thermometer. The inlet tube is connected to a
cylinder of chlorine through a bubble counter consisting of a
500-ml. wash bottle which contains about
200 ml. of concentrated sulfuric acid. The outlet tube is connected with a
gas trap in which the evolved
hydrochloric acid is absorbed by running water. It is best to set up the apparatus under a good
hood.
In the flask are placed
240 g. (2 moles) of acetophenone and
1 l. of glacial acetic acid. The thermometer is adjusted so that it extends considerably below the surface of the solution, and
chlorine is admitted at such a rate that the temperature does not exceed 60° (Note
1). Chlorination is continued until an excess of the halogen has been absorbed. This requires about 5 hours; completion of the reaction is indicated by the development of a yellow color. The reaction mixture is poured over 6 l. of crushed ice in a
2-gal. jar. The mixture is stirred several times (Note
2) and allowed to stand until the ice has melted. The
dichloroacetophenone, which separates as a heavy lachrymatory oil, is removed. The yield is
340–370 g. (
90–97%). This product, containing only a few per cent of water and
acetic acid, is pure enough for the preparation of
mandelic acid. It may be purified by adding about
100 ml. of benzene, removing the water and
benzene by distillation, and fractionally distilling the residual oil under reduced pressure. There is obtained
302–356 g. (
80–94%) of a colorless oil boiling at
132–134°/13 mm. (
142–144°/25 mm.).
B.
Mandelic acid. In a
2-l. three-necked round-bottomed flask, fitted with an
efficient mechanical stirrer, a
dropping funnel, and a thermometer, is placed
156 g. (3.9 moles) of sodium hydroxide dissolved in 1.4 l. of water. The solution is warmed to 60° (Note
3), vigorous stirring is begun, and
200 g. (1.06 moles) of dichloroacetophenone (either crude or distilled) is added from the dropping funnel. The
dichloroacetophenone is added slowly at first so that the temperature does not exceed 65°. The addition requires about 2 hours (Note
4). Stirring is continued for 1 hour longer while the temperature is maintained at 65° by means of a
water or steam bath. After addition of
170 ml. of 12 M hydrochloric acid (Note
5), the solution is extracted with
ether. The
continuous extractor shown in
.htmFig. 18 is very useful for this purpose. About
250–300 ml. of ether is used, and the extraction is continued until no more material is obtained. With this apparatus, about
130 g. of crude
mandelic acid is recovered after 24 hours, and 150 g. after 48 hours. The volume of liquid in the larger flask must be great enough so that, when
250–300 ml. of ether is used for the extraction, there will be a continuous overflow from the larger to the smaller flask; the latter serves as the "boiler."
Fig. 18.
The
ether extracts are transferred to a
1-l. round-bottomed flask, the
ether is removed by distillation, and the residue of crude
mandelic acid is dried by warming it on a steam bath under the vacuum of a
water pump. About
400 ml. of benzene is added, and the mixture is distilled until 100 ml. of distillate is collected. The acid in the residual mixture is brought completely into solution by the addition of
6–10 ml. of ethanol. The hot solution is then filtered through a
warm Büchner funnel, and the filtrate is cooled overnight at 6°. The first crop of pure
mandelic acid weighs
100–120 g. A second crop is obtained by evaporation of the mother liquor to about one-fourth its volume; this weighs
20–40 g. The total yield is
136–144 g. (
85–90% based on the
dichloroacetophenone, or
76–87% based on the
acetophenone). The white crystalline product melts at
115–117° (Note
6).
2. Notes
2. Stirring results in a better separation of
acetic acid from the oil and prevents the formation of an emulsion.
3. At lower temperatures, hydrolysis is slow.
4. If the temperature becomes much higher, side reactions occur and loss in yield and purity results. The heat of reaction is sufficient to maintain the required temperature.
5. If the reaction mixture is cooled at this point, some of the
mandelic acid may crystallize. If this happens, the precipitate should not be filtered, as it is contaminated with
sodium chloride.
3. Discussion
α-C14-Mandelic acid has been prepared from
α-C14-phenylglyoxal, and from
α-C14-α,α-dibromoacetophenone.
13 α-C13-Mandelic acid has been prepared from
α-C13-α,α-dibromoacetophenone.
14
This preparation is referenced from:
Copyright © 1921-2002, Organic Syntheses, Inc. All Rights Reserved