Organic Syntheses, CV 3, 536
Submitted by L. F. Audrieth and M. Sveda.
Checked by Homer Adkins and William H. Bateman.
1. Procedure
One hundred and forty-six grams (0.96 mole) of mandelic acid is dissolved in
440 ml. (6.2 moles) of acetone, and the resulting solution is placed in a
2-l. three-necked flask fitted with an
efficient stirrer, a
dropping funnel, and a
thermometer. The reaction flask is placed in an
ice-salt bath, and
98 g. of concentrated sulfuric acid (sp. gr. 1.84) is added through the dropping funnel at such a rate that the temperature does not exceed −10°. The reaction mixture is then poured into an ice-cold solution of
sodium carbonate containing 200 g. of the anhydrous salt in 1800 ml. of water. The
mandelic acid-acetone condensation product precipitates from the solution. The curdy product is washed by grinding with ice water (200 ml.) and is then filtered and dried over
calcium chloride under reduced pressure. The crude product weighs
181 g. (Note
1).
The
mandelic acid-acetone condensation product is added in small portions to about
1.8 l. of liquid ammonia (Note
2) contained in two
silvered 1-l. Dewar flasks. Each flask is fitted with a
stopper containing a
capillary tube to serve as an ammonia outlet. The ammonolysis is allowed to proceed overnight, after which the contents of the flasks are poured into open beakers to facilitate rapid evaporation of the liquid
ammonia.
After the
ammonia has been removed to a point where a pulverulent mass remains, the product is treated with
475 ml. of hot absolute ethanol and the resulting solution is filtered through a
hot funnel to remove insoluble impurities. The filtrate is cooled in an
ice bath to give about
90 g. of glistening white crystals of
mandelamide melting at
132° (
62% based upon the
mandelic acid) (Note
3) and (Note
4).
2. Notes
1. The crude product contains varying quantities of
sodium carbonate and
sodium sulfate, which are difficult to remove. These impurities are insoluble in liquid
ammonia; consequently the crude compound can be ammonolyzed without further purification. The
mandelic acid-acetone condensation product may be purified by recrystallization from absolute
ethanol; it then melts at
45°.
2. The solubility of the
mandelic acid-acetone condensation compound in liquid
ammonia at its boiling point is approximately 10 g. per 100 ml.
3. Additional quantities of
mandelamide may be obtained by concentrating the ethanolic mother liquor carefully.
4. This method is generally applicable to the preparation of the amides of α-hydroxy acids.
3. Discussion
Mandelamide has been prepared by treating the ethyl ester with concentrated aqueous
ammonia,
1,2 and a saturated
ethanolic solution of ammonia has been used to effect ammonolysis of the methyl ester.
3 Esters of
mandelic acid were treated with liquid
ammonia at its boiling point;
4 this procedure was improved by use of
ammonia at superatmospheric pressures and higher temperatures.
5 The procedure described in this synthesis was first used by Ôeda.
6
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