A Publication
of Reliable Methods
for the Preparation
of Organic Compounds
Annual Volume
Org. Synth. 1955, 35, 3
DOI: 10.15227/orgsyn.035.0003
[o-Toluidine, 6-nitro-]
Submitted by John C. Howard1
Checked by Charles C. Price and Joseph D. Berman.
1. Procedure
A 1-l. three-necked flask is fitted with a sealed Hershberg stirrer, a reflux condenser, and a dropping funnel. The flask is charged with 650 ml. of acetic anhydride, and 107 g. (107 ml., 1 mole) of o-toluidine (Note 1) is introduced from the dropping funnel. The mixture becomes very warm. After the amine has been completely added, the solution is cooled to 12–13° in an ice-salt bath (Note 2). During the cooling, the dropping funnel and condenser are replaced by another dropping funnel containing 126 ml. (2 moles) of 70% nitric acid and a thermometer which can be read to within 0.5° in the range from 10° to 20° (Note 3).
The nitric acid is added drop by drop to the cold slurry at a rate which maintains the temperature carefully within the limits of 10–12° (Note 4). If the temperature persists in dropping, the addition is stopped after about 5 minutes. The ice bath is removed until the temperature rises 0.5°, the ice-salt bath is replaced, and addition is continued. As the reaction progresses, the acetotoluide which may have precipitated redissolves, and the solution becomes deeply colored. The addition is complete in 1–2 hours, and the nitro compounds may start to separate.
The solution is poured, with stirring, into 3 l. of ice water. The mixture of 4- and 6-nitroacetotoluides precipitates as a creamcolored solid which is collected on a large Büchner funnel. After thorough washing with four 500-ml. portions of ice water, the precipitate is partly dried by suction (Note 5). The moist product is then placed in a steam-distillation apparatus (Note 6), covered with 300 ml. of concentrated hydrochloric acid, and heated until the mixture boils. The acetotoluides are rapidly hydrolyzed, and the solution becomes dark red. Steam is then introduced, and the distillation is thus continued until 36 l. of distillate has been collected (Note 7) and (Note 8). The 2-amino-3-nitrotoluene, which separates as bright orange needles when the distillate is cooled, is collected on a large Büchner funnel. The dried product amounts to 75–84 g. (49–55%), m.p. 92–94°. The product may be further purified by a second steam distillation. Ten grams of the amine is distilled from 150 ml. of water, and 3 l. of distillate is collected, yielding 8.7 g. of 2-amino-3-nitrotoluene, m.p. 95–96° (cor.).
2. Notes
1. Commercially available o-toluidine, b.p. 75–77°/10 mm., is suitable. Redistillation of this material gave no significantly better results. The checkers obtained a 42% yield of 2-amino-3-nitrotoluene using practical grade o-toluidine directly, and a 57% yield after redistillation.
2. The flask should be immersed up to the neck in the slurry of ice and salt. During the cooling, the acetotoluide may suddenly precipitate, immobilizing the stirrer; a few turns manually break up the mass of crystals and allow the stirring to be continued.
3. A low-temperature thermometer with a range from −15° to +50° is suitable.
4. If the temperature is allowed to rise above 18°, violent if not explosive decomposition may ensue.
5. The precipitate can be air-dried to a constant weight of 150–160 g.
6. An efficient steam-distillation apparatus such as that described by Fieser2 is recommended. A 12-l. round-bottomed flask cooled in a tub of ice serves as the receiver, which is equipped with an auxiliary vertical condenser attached to a gas absorption trap3 to accommodate the hydrogen chloride which distils first.
7. The third 12-l. portion yields about 20 g. of 2-amino-3-nitrotoluene. The residue in the steam-distillation flask, about 20 g. of crude 2-amino-5-nitrotoluene, solidifies when cooled and may be separated by filtration. It can be recrystallized from 2 l. of hot water, yielding 14–15 g. of yellow plates, m.p. 130–131° (cor.).
8. Instead of separating the mixture of isomers by the slow steam distillation, one may employ the procedure of Wepster and Verkade.4 In the latter, the product from the nitration of o-methylacetanilide is treated with the Witt-Utermann solution,5 which consists of a water-alcohol solution of potassium hydroxide. 2-Acetylamino-5-nitrotoluene is insoluble in this solution, while the 3-nitro isomer is soluble and may be recovered in high yield and a good state of purity by acidification of the red filtrate. Hydrolysis of the acetyl derivatives affords 2-amino-5-nitro-and 2-amino-3-nitrotoluene.
3. Discussion
2-Amino-3-nitrotoluene has been prepared by the nitration of oxalotoluide6 and by the nitration of o-acetotoluide in acetic acid with fuming nitric acid,7 with a mixture of nitric and sulfuric acid,8 or with metal nitrates.9
This preparation is referenced from:

References and Notes
  1. Cornell University, Ithaca, New York.
  2. Fieser, Experiments in Organic Chemistry, 3rd ed., p 257 (Figs. 45.4 and 45.5), D. C. Health and Company, Boston, Massachusetts, 1955.
  3. Org. Syntheses Coll. Vol. 2, 4 (1943).
  4. Wepster and Verkade, Rec. trav. chim., 68, 77 (1949).
  5. Witt and Utermann, Ber., 39, 3901 (1906).
  6. Hadfield and Kenner, Proc. Chem. Soc., 30, 253 (1914).
  7. Cohen and Dakin, J. Chem. Soc., 79, 1127 (1901).
  8. McGookin and Swift, J. Soc. Chem. Ind., 58, 152 (1939).
  9. Kyryacos and Schultz, J. Am. Chem. Soc., 75, 3597 (1953).

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

4- and 6-nitroacetotoluides

2-amino-5-nitro-and 2-amino-3-nitrotoluene

nitric and sulfuric acid

hydrogen chloride,
hydrochloric acid (7647-01-0)

acetic acid (64-19-7)

acetic anhydride (108-24-7)

nitric acid (7697-37-2)

potassium hydroxide (1310-58-3)

2-amino-5-nitrotoluene (99-52-5)

o-Toluidine, 6-nitro- (570-24-1)

acetotoluide (103-89-9)



o-toluidine (95-53-4)

o-acetotoluide (120-66-1)