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Org. Synth. 1923, 3, 11
DOI: 10.15227/orgsyn.003.0011
p-AMINOPHENYLACETIC ACID
[α-Toluic acid, p-amino-]
Submitted by G. Ross Robertson
Checked by H. T. Clarke and J. H. Bishop.
1. Procedure
A 1500-cc. flask is fitted with a two-holed rubber stopper carrying a glass tube which ends below the middle of the flask. The second hole is fitted with a common glass stopcock (Note 1). To the flask is added 500 cc. of 6 N aqueous ammonia (sp. gr. about 0.95), and 100 g. (0.55 mole) of p-nitrophenylacetic acid (p. 406) is now slowly introduced, with shaking. The flask is then placed in an ice bath, and the mixture saturated with hydrogen sulfide, the temperature being held below 50°.
The stopper is removed from the reaction flask, and the solution of ammonium p-aminophenylacetate gently boiled under the hood until nearly all the excess hydrogen sulfide and ammonia have escaped. The solution changes from a dark orange-red to a pale yellow. The deposited sulfur is filtered off by suction, and 40 cc. of glacial acetic acid rapidly stirred into the hot filtrate. The p-aminophenylacetic acid which crystallizes out weighs 69–70 g., but it is contaminated with a small amount of free sulfur. On evaporating the mother liquor to a small volume, about 5 g. more can be obtained. The crude material is recrystallized from 4 l. of distilled water, 69–70 g. (83–84 per cent of the theoretical amount) of a product which melts at 199–200° being thus obtained (Note 2).
2. Notes
1. The use of a stopcock in the reaction flask during the saturation with hydrogen sulfide permits the occasional expulsion of hydrogen gas, which would otherwise accumulate. Apparently, commercial ferrous sulfide contains free iron as an impurity.
2. The procedure avoids the troubles of filtration incidental to the method of reduction with ferrous sulfate and ammonia, and the yield is better. Inasmuch as the only by-product is the very soluble ammonium acetate, a large yield can be secured by close evaporation.
3. Discussion
p-Aminophenylacetic acid can be prepared by the hydrolysis of p-aminobenzyl cyanide with concentrated hydrochloric acid,1 and by the reduction of p-nitrophenylacetic acid with tin and hydrochloric acid2 or with ferrous sulfate and ammonia.3 Reduction of p-nitrophenylacetic acid with a platinum oxide catalyst is reported to furnish a quantitative yield of p-aminophenylacetic acid, but, because of more favorable solubilities, it is recommended that the ethyl ester be reduced and the reduction product then hydrolyzed to the acid.4
This preparation is referenced from:

References and Notes
  1. Friedländer, Ber. 17, 237 (1884); Gabriel, Ber. 15, 835 (1882).
  2. Radziszewski, Ber. 2, 209 (1869); Bedson, J. Chem. Soc. 37, 92 (1880).
  3. Jacobs and Heidelberger, J. Am. Chem. Soc. 39, 1437 (1917); Robertson and Stieglitz, ibid. 43, 180 (1921).
  4. Ferber and Bendix, Ber. 72, 839 (1939).

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

hydrochloric acid (7647-01-0)

acetic acid (64-19-7)

ammonia (7664-41-7)

ammonium acetate (631-61-8)

hydrogen (1333-74-0)

iron (7439-89-6)

hydrogen sulfide (7783-06-4)

tin (7440-31-5)

α-Toluic acid (65-85-0)

sulfur (7704-34-9)

ferrous sulfide

ferrous sulfate (13463-43-9)

platinum oxide

ethyl ester (141-97-9)

p-AMINOPHENYLACETIC ACID (1197-55-3)

p-Nitrophenylacetic acid (104-03-0)

ammonium p-aminophenylacetate

p-aminobenzyl cyanide (3544-25-0)