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Org. Synth. 1925, 4, 1
DOI: 10.15227/orgsyn.004.0001
ACETYLMANDELIC ACID and ACETYLMANDELYL CHLORIDE
[(Mandelic acid, acetate) (Mandelyl chloride, acetate)]
Submitted by F. K. Thayer
Checked by Roger Adams and E. E. Dreger.
1. Procedure
(A) In a 500-cc. Claisen distilling flask with a low side tube connected to a condenser, are placed 105 g. (0.69 mole) of mandelic acid (p. 336) (m.p. 118°) and 151 g. (137 cc., 1.92 moles) of acetyl chloride. A reaction sets in without the application of heat (Note 1). As soon as a clear solution results, the flask is warmed on a water bath and the excess acetyl chloride is distilled. The last trace of acetyl chloride may be removed by prolonged drying in a vacuum. The acetylmandelic acid then crystallizes in large, round, white clusters after one or two days' standing. The yield is 130–133 g. (97–99 per cent of the theoretical amount) (Note 2).
(B) To the crude acetylmandelic acid still containing some acetyl chloride obtained as described above, is added 250 g. (149 cc., 2.1 moles) of thionyl chloride. The reaction starts at once without warming but it is necessary to reflux for four hours to complete the reaction (Note 3). The excess thionyl chloride is then distilled and the residue distilled under reduced pressure (Note 4). The yield is 115–120 g. (79–82 per cent of the theoretical amount) of almost colorless liquid boiling at 125–130°/10 mm. (150–155°/33 mm.).
2. Notes
1. Occasionally the application of a little heat is necessary to bring about a more rapid acetylation.
2. The melting points given in the literature range from 39 to 80°. The acetylmandelic acid is difficult to crystallize but may be purified from benzene or chloroform, preferably the former. The product thus obtained melts at about 79–80°.
3. Prolonged refluxing of the acetylmandelic acid with the thionyl chloride tends to lower the yield.
4. The boiling point of acetylmandelyl chloride has been reported1 as 129°/10 mm. The pressure should be reduced as low as possible, to avoid the formation of tar during the distillation.
3. Discussion
Acetylmandelic acid can be prepared by the action of acetyl chloride1 or acetic anhydride2 on mandelic acid.
Acetylmandelyl chloride can be prepared by the action of phosphorus pentachloride1 or thionyl chloride3 on acetylmandelic acid.

References and Notes
  1. Anschütz and Böcker, Ann. 368, 57, 59 (1909).
  2. Kaufler and Herzog, Ber. 42, 3872 (1909).
  3. v. Braun and Müller, Ber. 51, 244 (1918).

Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

Benzene (71-43-2)

acetic anhydride (108-24-7)

phosphorus pentachloride (10026-13-8)

Acetylmandelic acid

Acetylmandelyl chloride (1638-63-7)

Mandelic acid, acetate (5438-68-6)

Mandelyl chloride, acetate

Mandelic acid (90-64-2)

acetyl chloride (75-36-5)

thionyl chloride (7719-09-7)

chloroform (67-66-3)