Org. Synth. 1936, 16, 4
DOI: 10.15227/orgsyn.016.0004
[Aniline, 3,4-dimethoxy-]
Submitted by J. S. Buck and W. S. Ide.
Checked by John R. Johnson and H. B. Stevenson.
1. Procedure
In a 5-l. flask fitted with a mechanical stirrer are placed 1.8 kg. (1.6 moles) of fresh 3 per cent hydrogen peroxide solution, 100 g. of 25 per cent potassium hydroxide solution, and 57 g. (0.35 mole) of veratronitrile (p. 622). The mixture is warmed slowly to 45°, with stirring, and the source of heat is then withdrawn. The reaction proceeds with evolution of oxygen, and the temperature continues to rise (Note 1). The amide soon begins to separate; in about fifty minutes the reaction is complete and the temperature begins to fall. The mixture is cooled to 3–5° and allowed to remain in the cooling bath for one and one-half to two hours. The white crystalline product is filtered with suction and dried in the air. The veratric amide melts at 162.5–163.5° and weighs 55–58 g. (87–92 per cent of the theoretical amount).
An alkaline solution of sodium hypochlorite is prepared by passing chlorine (0.412 gram for each gram of the amide) (Note 2) into a mixture of 300 g. of cracked ice and a cold solution of 80 g. of sodium hydroxide in 500 cc. of water, contained in a 2-l. round-bottomed flask. The whole of the veratric amide (55–58 g.) is added in one portion, and the mixture is warmed slowly in a water bath, with mechanical stirring. The material soon darkens in color, and at 50–55° (internal temperature) oily droplets begin to separate. The temperature is raised gradually to 70° and maintained at this point for one hour. A solution of 120 g. of sodium hydroxide in 120 cc. of water is added slowly, and the temperature is increased to 80° for an additional hour.
Upon cooling the mixture, the oily layer of amine solidifies to a red crystalline mass. The crude amine is filtered with suction, washed with two 60-cc. portions of ice-cold water, pressed thoroughly, and transferred to an ordinary 125-cc. Claisen flask. The filtrate is extracted with three 60-cc. portions of benzene, the extracts are transferred separately to the Claisen flask, and the benzene is distilled at atmospheric pressure (Note 3). The residual amine is distilled under reduced pressure and is collected at 172–174°/24 mm. (Note 4). The distillate solidifies quickly to a mass of colorless crystals which melt sharply at 87.5–88° (Note 5). From 58 g. (0.32 mole) of veratric amide there is obtained 39–40 g. (80–82 per cent of the theoretical amount) of 4-aminoveratrole.
2. Notes
1. A large amount of frothing occurs, and the temperature rises to 52–55° during the reaction. The flask should be removed at intervals and shaken by hand to bring the material carried up by the froth into contact with the solution.
2. The quantity of chlorine indicated is 5 per cent more than the theoretical amount. The chlorine may be obtained from a cylinder, but for small amounts it is more accurate to generate chlorine by treating a weighed amount of potassium permanganate with an excess of concentrated hydrochloric acid (0.367 g. KMnO4 ≎ 0.412 g. Cl2). For 55–58 g. of veratric amide the weight of permanganate to be used is 20.2–21.3 g.
For generating the chlorine, the requisite weight of potassium permanganate is placed in a 500-cc. distilling flask fitted with a separatory funnel and suspended so that the flask can be agitated. Concentrated hydrochloric acid (about 130 cc. is required) is allowed to drop slowly upon the permanganate crystals, and as the reaction progresses the flask is heated. After all the acid has been added the mixture is boiled gently for a few minutes to expel the last portions of chlorine, and the delivery tube is removed rapidly from the alkaline hypochlorite solution to prevent the solution from being sucked back into the generator. A safety bottle should be inserted between the side tube of the generator and the tube which delivers the chlorine into the alkali.
3. Distillation of the benzene extracts in this way serves to remove the water, and in the subsequent distillation of the amine no watery fore-run is obtained.
4. Since the aminoveratrole tends to solidify in the side tube of the distilling flask, it is advisable to distil the material rapidly and to employ a bath temperature about 60° higher than that of the distilling vapor. Care must be taken to avoid contaminating the distillate with a small amount of colored material which comes over if the distillation is carried too far.
5. The melting point of 4-aminoveratrole obtained by reduction of 4-nitroveratrole is reported as 85–86°.1 The amine discolors on exposure to air and light; it should be stored in a sealed, dark container.
3. Discussion
4-Aminoveratrole has been prepared by the reduction of 4-nitroveratrole with tin,1, 2 or stannous chloride,3 and hydrochloric acid. The present procedure is based upon a method used for the preparation of aminopiperole (3,4-methylenedioxyaniline).4
This preparation is referenced from:

References and Notes
  1. Moureu, Bull. soc. chim. (3) 15, 647 (1896).
  2. Simonsen and Rau, J. Chem. Soc. 113, 28 (1918); Pollecoff and Robinson, ibid. 113, 645 (footnote) (1918).
  3. Heinisch, Monatsh. 15, 232 (1894).
  4. Rupe and Majewski, Ber. 33, 3401 (1900).

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


hydrochloric acid (7647-01-0)

Benzene (71-43-2)

sodium hydroxide (1310-73-2)

potassium permanganate (7722-64-7)

oxygen (7782-44-7)

tin (7440-31-5)

stannous chloride

chlorine (7782-50-5)

potassium hydroxide (1310-58-3)

hydrogen peroxide (7722-84-1)


sodium hypochlorite (7681-52-9)

Aniline, 3,4-dimethoxy- (6315-89-5)

Veratronitrile (2024-83-1)

Veratric amide (1521-41-1)


4-nitroveratrole (709-09-1)

3,4-methylenedioxyaniline (14268-66-7)