Organic Syntheses, CV 3, 661
Submitted by Paul E. Fanta and D. S. Tarbell.
Checked by W. E. Bachmann and N. C. Deno.
1. Procedure
A.
2-Nitro-4-methoxyacetanilide. In a
2-l. three-necked, round-bottomed flask equipped with a
mechanical stirrer and a
thermometer are placed
123 g. (1 mole) of p-anisidine (Note
1),
300 ml. of glacial acetic acid, and 217 ml. of water. Stirring is started, and, when the
p-anisidine has dissolved, 350 g. of ice is added. When the temperature reaches 0–5°,
103 ml. (1.1 moles) of acetic anhydride is added all at once with rapid stirring. Within several seconds the contents of the flask set to a crystalline mass and the temperature rises to 20–25°. The flask is heated on a
steam bath until the crystalline material dissolves and is then cooled with stirring to 45°, at which temperature crystals begin to separate. An
ice bath is applied, and
100 ml. (55% excess) of concentrated nitric acid (sp. gr. 1.42) is added all at once. The temperature rises rapidly to 70° and soon begins to fall. By suitable adjustment of the cooling bath the temperature is maintained at 60–65° for 10 minutes and then brought down to 25° in the course of 10 minutes (Note
2).
The solution is chilled overnight in an ice chest, and the precipitated yellow crystals are collected on a
19-cm. Büchner funnel. The crystals are washed with 270 ml. of ice-cold water and pressed as dry as possible with a
rubber dam. The filter cake can be dried (Note
3) in air or in a
vacuum desiccator over
calcium chloride and
soda lime. The yield of
2-nitro-4-methoxyacetanilide melting at
116–116.5° is
158–168 g. (
75–79%).
B.
2-Nitro-4-methoxyaniline. A mixture of
160 g. of 2-nitro-4-methoxyacetanilide and 250 ml. of cold Claisen's alkali (Note
4) in a
2-l. beaker is stirred and warmed on a steam bath for 15 minutes; it first becomes liquid and then sets to a thick, red paste. After the addition of 250 ml. of hot water the mixture is stirred and digested on a steam bath for an additional 15 minutes and then cooled to 0–5°. The product is collected on a 19-cm. Büchner funnel, washed with three 160-ml. portions of ice-cold water, and pressed as dry as possible with a rubber dam. The yield of vacuum-dried product melting at
122.5–123° is
122–124 g. (
95–97%).
2. Notes
1.
Eastman Kodak Company's Practical grade of p-anisidine was used.
2. In a run in which the mixture was allowed to cool spontaneously from 65° the product became dark.
3. Drying is unnecessary if the
2-nitro-4-methoxyacetanilide is used in step B. The material may be recrystallized with
97% recovery from dilute aqueous
ethanol (2 ml. of 95% ethanol and 4 ml. of water per gram). The product so obtained melts at
116.5–117°.
4. Claisen's alkali is prepared by dissolving
88 g. of potassium hydroxide in 63 ml. of water, cooling, and diluting to 250 ml. with
methanol.
3. Discussion
2-Nitro-4-methoxyacetanilide has been prepared by the nitration of
p-acetaniside.
1 2 3 4 The procedure described for the nitration is essentially that used by Lothrop.
4
Copyright © 1921-2002, Organic Syntheses, Inc. All Rights Reserved