A Publication
of Reliable Methods
for the Preparation
of Organic Compounds
Annual Volume
Org. Synth. 1947, 27, 15
DOI: 10.15227/orgsyn.027.0015
[Acetic acid, aminoöxy-, hydrochloride]
Submitted by H. S. Anker and H. T. Clarke.
Checked by H. R. Snyder and Peter Kovacic.
1. Procedure
A. Acetone carboxymethoxime. A mixture of 612 g. (4.4 moles) of bromoacetic acid (Note 1) and 500 g. of crushed ice is chilled in an ice-salt bath and made distinctly alkaline to litmus with sodium hydroxide (about 440 g. of a 40% solution). During the neutralization an additional 500 g. of ice is added. To the solution are then added 292 g. (4.0 moles) of acetoxime1 and 440 g. of 40% sodium hydroxide (4.4 moles), the temperature being held below 20° during the addition of the alkali. The mixture is then allowed to flow dropwise, during 3–4 hours, through the inner tube of a steam-heated Liebig condenser (jacket 75 cm. long; inner tube 10-mm. diameter; angle of inclination about 20°) into a 5-l. round-bottomed flask cooled with running water (Note 2). The resulting solution is extracted three times with 500-ml. quantities of freshly distilled peroxide-free ether (Note 3), and the aqueous solution is then cooled and made strongly acid by the addition of 500 ml. of concentrated hydrochloric acid (6 moles). During the acidification the temperature should not rise above 15°. The solution is saturated with sodium chloride and immediately extracted with six successive 1.5-l. portions of peroxide-free ether. The ether is distilled from the combined ethereal extracts, and the residue, consisting of the crude acetone carboxymethoxime (333–345 g.), is used for the next step. The acetone carboxymethoxime may be purified by distillation under reduced pressure, the fraction boiling at 95–97°/1 mm. (Note 4) being collected (Note 5). The yield is 300 g. (57%) of a colorless product melting at 76°.
B. Carboxymethoxylamine hemihydrochloride. The crude acetone carboxymethoxime is dissolved in about twice its weight of benzene; the solution is filtered and freed of benzene by distillation under reduced pressure from a steam bath. To a solution of 200 g. (1.52 moles) of the residue in 1 l. of water, in a 5-l. flask, are added 2 mg. of hydroquinone and 1 l. of concentrated hydrochloric acid. The flask is connected with a condenser, and steam is passed through the solution until acetone no longer comes over (30–40 minutes). The solution is concentrated under reduced pressure to a volume of 180–220 ml., and 400 ml. of isopropyl alcohol is added. The solution is then stored for 12 hours in the icebox, and the crystals that separate are collected on a Büchner funnel and washed with cold isopropyl alcohol. Further crops are obtained by concentrating the mother liquors and adding isopropyl alcohol. The crude product (120–135 g.) may be recrystallized (Note 6) with very little loss by dissolving it in twice its weight of warm (50°) water (Note 7), adding 2 volumes of isopropyl alcohol, and again chilling in an icebox. Further small quantities can be recovered from the mother liquors by systematic repetition of the process described. The yield is 110–120 g. (66–72%) of white crystals which melt with decomposition at 152–153° (Note 8) and (Note 9).
2. Notes
1. Chloroacetic acid gives a poorer yield (46–49%) of acetone carboxymethoxime, and the crude product is more difficult to purify.2
2. By this procedure, the reaction takes place in a few seconds, and the formation of by-products is minimized. If the solution of the reactants is heated in bulk, the reaction temperature cannot be controlled, and a lower yield is obtained of a dark product which, however, can be purified by distillation under reduced pressure.
3. The unchanged acetoxime extracted by the ether amounts to 14–24 g. (5–8%).
4. The temperature of the vapor, during distillation under apparently comparable conditions, may differ from run to run by as much as 20°. The temperature range of 95–97° is the lowest observed for 1-mm. pressure. Boiling ranges of 110–118°/1 mm. have been reported.
5. No carbonization and only slight formation of hydrogen cyanide, which occurs extensively during the distillation of preparations from chloroacetic acid,2 are observed.
6. The use of decolorizing carbon should be avoided, as some brands appear to contain impurities that catalyze decomposition to ammonium chloride.
7. If the resulting aqueous solution is cooled to 0° before the addition of isopropyl alcohol, about one-third of the product crystallizes in very pure form.
8. The melting point depends on the rate at which the sample is heated. When the temperature is raised in the ordinary way the material melts (with evolution of gas) at 152–153°; when the bath is heated to 150° before the sample is inserted, the melting point is 159°. On the other hand, when a sample is held between 140° and 145° it melts after about 6 minutes. Decomposition evidently plays a large part in the matter.
9. The hydrolysis of acetone carboxymethoxime may also be accomplished on a smaller scale (10 g.) by a simplified procedure as described by Lott.3
3. Discussion
Carboxymethoxylamine (also called hydroxylamine-O-acetic acid), which is of value for the isolation of ketones,4 has been prepared by the hydrolysis of ethylbenzhydroximinoacetic acid5 and of ethyl benzhydroximinoacetate.6 The present method is a modification of that described by Borek and Clarke.2

References and Notes
  1. Org. Syntheses Coll. Vol. 1, 318 (1941).
  2. Borek and Clarke, J. Am. Chem. Soc., 58, 2020 (1936).
  3. Lott, J. Am. Chem. Soc., 70, 1972 (1948).
  4. Anchel and Schoenheimer, J. Biol. Chem., 114, 539 (1936).
  5. Werner, Ber., 26, 1567 (1893); Werner and Sounenfeld, Ber., 27, 3350 (1894).
  6. Kitagawa and Takani, J. Biochem. Japan, 23, 181 (1936).

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

Carboxymethoxylamine hemihydrochloride

Acetone carboxymethoxime

hydrochloric acid (7647-01-0)

Benzene (71-43-2)

ether (60-29-7)

ammonium chloride (12125-02-9)

sodium hydroxide (1310-73-2)

hydroquinone (123-31-9)

sodium chloride (7647-14-5)

hydrogen cyanide (74-90-8)

chloroacetic acid (79-11-8)

acetone (67-64-1)

decolorizing carbon (7782-42-5)

isopropyl alcohol (67-63-0)


Bromoacetic acid (79-08-3)

hydroxylamine-O-acetic acid (645-88-5)

ethylbenzhydroximinoacetic acid

ethyl benzhydroximinoacetate

Acetic acid, aminooxy-, hydrochloride (2921-14-4)