Organic Syntheses, CV 6, 797
Submitted by S. Zen, M. Koyama, and S. Koto
1.
Checked by M. Ando and G. Büchi.
1. Procedure
Caution!
Benzene has been identified as a carcinogen; OSHA has issued emergency standards on its use. All procedures involving
benzene should be carried out in a
well-ventilated hood, and glove protection is required.
A.
Dipotassium salt of nitroacetic acid. A
3-l., three-necked, round-bottomed flask equipped with a sealed
mechanical stirrer, a
condenser fitted with a
calcium chloride drying tube, and a
pressure-equalizing dropping funnel is charged with a fresh solution of
224 g. of potassium hydroxide in 112 g. of water. From the dropping funnel is added, over 30 minutes (Note
1),
61 g. (1.0 mole) of nitromethane. The reaction mixture is heated to reflux for 1 hour in an
oil bath maintained at approximately 160° (Note
2). After cooling to room temperature, the precipitated crystalline product is filtered, washed several times with
methanol, and dried in a
vacuum desiccator under reduced pressure, yielding
71.5–80.0 g. (
79–88%) of the
dipotassium salt of nitroacetic acid, m.p.
262° (dec.).
B.
Methyl nitroacetate. A
2-l., three-necked, round-bottomed flask equipped with a sealed mechanical stirrer, a pressure-equalizing dropping funnel fitted with a calcium chloride drying tube, and a
thermometer is charged with
70 g. (0.39 mole) of finely powdered dipotassium salt of nitroacetic acid (Note
4) and
465 ml. (11.6 moles) of methanol.
The reaction mixture is cooled to −15° ± 3° and
116 g. (1.16 moles) of concentrated sulfuric acid is added with vigorous stirring over approximately 1 hour at such a rate that the reaction temperature is maintained at −15°. The reaction mixture is allowed to warm to room temperature over a 4-hour period and stirred for another 4 hours at room temperature. The precipitate is removed by suction filtration, and the filtrate is concentrated on a
rotary evaporator at 30–40°. The residual oil is dissolved in
benzene and washed with water. The organic layer is dried over anhydrous
sodium sulfate, and the
benzene is removed by distillation. Further distillation under reduced pressure yields
30–32 g. (
66–70%) of
methyl nitroacetate, b.p.
80–82° (8 mm.),
111–113° (25 mm.) (Note
5).
2. Notes
1. The reaction mixture heats to 60–80° during the addition of
nitromethane. The mixture may require external heating to maintain this temperature. The initial, yellowish color begins to turn red-brown and gradually deepens as
ammonia gas is liberated.
2. The reaction mixture should not be stirred mechanically during this period in order to avoid decomposition of the product.
3. This crude product is rather pure. It can and should be employed for the esterification step without further purification. Elemental analyses for C
2HO
4NK
2 were as follows;
calculated: C, 13.26; H, 0.56; N, 7.73; K, 43.16%,
found: C, 13.27; H, 0.57; N, 7.80; K, 42.68%. This is a hygroscopic crystalline powder and should be used immediately after drying. There is a report
2 regarding an explosion of the dry dipotassium salt prepared by another method. There is no evidence that this procedure produces the same unstable impurities.
4. This must be ground into a fine powder with a
mortar and pestle immediately prior to use.
5. The spectral properties of the product are as follows; IR (neat) cm.
−1: 1776, 1760;
1H NMR (CDCl
3), δ (multiplicity, number of protons, assignment): 3.83 (s, 3H, OC
H3), 5.20 (s, 2H, C
H2);
nD20 1.4260.
3. Discussion
This procedure
5 is an improvement in that the reaction time is reduced and the yield is improved by increasing the concentration of alkali.
The acid-catalyzed esterification has been accomplished with either
hydrochloric acid3 or
sulfuric acid;
6 an improvement on the Steinkopf method has been reported,
7 but the procedure lacks the simplicity of the present method.
Application of
sulfuric acid as the catalyst is considered more practical for esterification because of its higher boiling point, its incompatibility with
benzene, and the stability of
nitroacetic acid in the reaction mixture, which allows omission of the final neutralization step.
This preparation is referenced from:
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