Organic Syntheses, CV 5, 27
Submitted by John D. Hepworth
1
Checked by W. T. Nolan and V. Boekelheide.
1. Procedure
A.
Acetamidoacetone. A mixture of
75.0 g. (1.0 mole) of glycine (Note
1),
475 g. (485 ml., 6 moles) of pyridine (Note
1), and
1190 g. (1.1 l., 11.67 moles) of acetic anhydride (Note
1) and (Note
2) is heated under reflux with stirring for 6 hours (Note
3) in a
3-l., three-necked, round-bottomed flask. The
reflux condenser is replaced by one set for downward distillation, and the excess
pyridine,
acetic anhydride, and
acetic acid are removed by distillation under reduced pressure. The residue is transferred to a simple distillataion apparatus such as a
Claisen flask and is distilled to give
80–90 g. (
70–78%) of a pale yellow oil, b.p.
120–125° (1 mm.). This product is of satisfactory purity for use in step B.
B.
Aminoacetone hydrochloride. A mixture of
175 ml. of concentrated hydrochloric acid and 175 ml. of water is added to
52 g. (0.45 mole) of the acetamidoacetone from step A contained in a
1-l. round-bottomed flask. The mixture is boiled under reflux under a
nitrogen atmosphere (Note
4) for 6 hours. The resulting solution is concentrated using a
flash evaporator held below 60° and with the
condensation trap for solvent being cooled by a
dry ice-acetone bath. The dark red oily residue (
40–45 g.) is satisfactory for use in step C (Note
5).
C.
Aminoacetone semicarbazone hydrochloride. The product from step B is dissolved in
250 ml. of absolute alcohol in a
1-l. Erlenmeyer flask, and to this solution is added a solution of
48 g. of semicarbazide hydrochloride (Note
1) in 100 ml. of water. The mixture is allowed to stand at room temperature for 2 hours, the crystalline precipitate is collected by suction filtration, and the off-white product is washed on the filter with absolute
alcohol. The crystals, after air-drying, amount to
54–58 g. (
72–78%) and melt at
208–210°. The product is essentially pure and can be used for most purposes without further purification (Note
6).
2. Notes
3. It is necessary that the mixture actually boil under reflux or the yield may drop to 25–30%.
4. The checkers used high-purity
nitrogen. If ordinary commercial
nitrogen is employed, the
oxygen should be removed by passing the gas through Fieser's solution.
6. For further purification, the
semicarbazone hydrochloride may be recrystallized from aqueous
ethanol to give colorless crystals, m.p.
212°.
3. Discussion
4. Merits of the Preparation
Aminoacetone is a versatile starting material for many syntheses, particularly for the preparation of heterocycles. The present procedure describes a convenient method for its preparation in a form suitable for storage. The
aminoacetone can be generated from
aminoacetone semicarbazone hydrochloride in situ as needed.
Copyright © 1921-2002, Organic Syntheses, Inc. All Rights Reserved