Organic Syntheses, Coll. Vol. 5, p.839 (1973); Vol. 43, p.83 (1963).
Caution! The nitrating mixture consisting of fuming nitric acid
and acetic anhydride
is an extremely active one, and combinations of it and organic materials are potentially explosive. The nitration should be carried out behind adequate safety shields. Acetone cyanohydrin nitrate
is moderately explosive (Note 6)
and all operations with it, but particularly its distillation, should be carried out behind safety shields.
A. Acetone cyanohydrin nitrate
. White fuming nitric acid (106 ml., 158 g., 2.3 moles) (Note 1)
is added dropwise to 380 ml. (408 g., 4.00 moles) of acetic anhydride
at 3–5° contained in a 2-l. three-necked flask
fitted with a stirrer
, a thermometer
, and a dropping funnel
and immersed in an ice bath
. After the addition, which requires 45 minutes, the mixture is stirred at 5° for 15 minutes (Note 2)
. Acetone cyanohydrin (92 ml., 85 g., 1.00 mole (Note 3)
is added dropwise to the mixture at 5–10° over a 45-minute period. After the addition, the ice bath is removed and the mixture is allowed to warm to room temperature and is stirred there for 30 minutes. It is then poured into 600 g. of ice and water, and the resulting mixture is stirred for 90 minutes to dissolve the acetic anhydride
. Morpholine (34.8 g., 0.40 mole)
and 26 g. (0.20 mole) of acetone cyanohydrin nitrate
are mixed in a 50-ml. round-bottomed flask
equipped with a thermometer well. A condenser is attached, and the mixture is heated slowly. At about 60° an exotherm ensues that raises the temperature of the mixture to 110°. The mixture is allowed to cool to 80° and maintained there for 1 hour. It is poured into 200 ml. of 10% hydrochloric acid Caution! Do in a hood! (Note 8))
and extracted with three 100-ml. portions of methylene chloride (Note 9)
. The extracts are combined, washed successively with two 100-ml. portions of water, 100 ml. of 10% hydrochloric acid
, and 100 ml. of water, and dried over anhydrous magnesium sulfate
. The solvent is removed by evaporation on a water aspirator at room temperature to yield a pale-yellow oil (Note 10)
The oil is dissolved in 80 ml. of absolute ethanol
. The solution is cooled to 0–5°, causing white crystals of N-nitromorpholine
to precipitate; weight 15–17 g.
); m.p. 52–54° (Note 11)
This is 90% nitric acid
, d. 1.48–1.50. In order to remove dissolved nitrogen
oxides from it, 0.5 g. of urea
is added and the mixture is air-sparged for 20 minutes. The acid should be colorless before it is added to the acetic anhydride
The nitrating mixture should be colorless at this point. If it is not, 0.5 g. of urea
should be added and the mixture air-sparged until colorless.
Suitable acetone cyanohydrin can be purchased from the Rohm and Haas Co.
and other commercial sources, or it can be prepared as described in Organic Syntheses
Washing with the carbonate solution should be continued until the organic layer is free of acid. Traces of acid may cause extensive decomposition during the distillation.
Similar yields were observed in preparations on three times this scale.
The product obtained from this distillation usually contains small amounts of acetone cyanohydrin acetate
, as evidenced by an ester carbonyl band at 1740 cm.−1
in its infrared spectrum. This material does not interfere with the nitration reactions of the reagent. It may be removed by fractionation through a more efficient column.
This operation should be carried out in a good hood because hydrogen cyanide
is evolved at this point.
Occasionally this oil solidifies after removal of the last traces of solvent; in these instances it is necessary to warm the ethanol
slightly to effect solution.
In nitrating amines other than morpholine
, particularly on a larger scale, it may be desirable to carry out the reaction in acetonitrile
to control the temperature better.3
4. Merits of the Preparation
This synthesis of N-nitromorpholine
is representative of a rather general reaction for the preparation of both primary and secondary nitramines.3
It represents the simplest process for obtaining both types of compounds. The reaction is unique in that a nitration is carried out under neutral or alkaline conditions. Acetone cyanohydrin nitrate
may also be used for the nitration of many active methylene compounds.8
Copyright © 1921-, Organic Syntheses, Inc. All Rights Reserved