A Publication
of Reliable Methods
for the Preparation
of Organic Compounds
Annual Volume
Org. Synth. 1925, 4, 19
DOI: 10.15227/orgsyn.004.0019
Submitted by C. S. Marvel
Checked by Oliver Kamm
1. Procedure
The moist phenylhydroxylamine obtained from 1 kg. (8.1 moles) of nitrobenzene, by the procedure described on p. 445, is weighed and dissolved in 4.5 l. of ordinary ether (Note 1). The ether-insoluble material (sodium chloride and water) is also weighed, the difference between the two weighings being a fairly accurate measure of the amount of phenylhydroxylamine in solution.
The ether solution is filtered through a dry filter paper into a 5-l. round-bottomed flask which is fitted with an efficient mechanical stirrer and immersed in an ice-salt bath. When the temperature of the solution has fallen to 0° (Note 2), a rapid stream of dry ammonia, from a cylinder of the compressed gas, is passed into the solution.
After about fifteen minutes, the theoretical amount of freshly distilled n-butyl nitrite (95 g. for every 100 g. of phenylhydroxylamine) is added slowly through a dropping funnel (Note 3) and (Note 4). The addition of butyl nitrite usually requires about one hour (Note 5), during which time the stream of ammonia gas is continued in order that ammonia may always be in excess. If this precaution is not observed, a colored product will result. The temperature of the reaction mixture should be maintained below 10° and this may be done best by controlling the rate at which the butyl nitrite is added (Note 6). An appreciable rise in temperature will cause the volatilization of considerable quantities of ether and of ammonia (Note 7).
After the butyl nitrite has been added, the reaction mixture is stirred for about ten minutes longer in order to insure completion of the reaction, after which the cupferron is filtered off and washed several times with small portions of fresh ether. The product is spread on sheets of paper until all traces of ether have been lost, and is then stored in bottles where it is exposed to the vapors of ammonium carbonate. This may be done by protecting each cork with a double sheet of filter paper and placing a lump of ammonium carbonate between the cork and the filter paper (Note 8).
The yield of cupferron based on a given weight of phenylhydroxylamine averages 85–90 per cent of the theoretical amount.
2. Notes
1. The solvent ether may be replaced by benzene, but this modification offers no advantages for the preparation of cupferron on a laboratory scale.
2. The temperature must be kept low. If it is not, the material is generally colored brown and the reaction does not run smoothly. Probably the most important factor in securing successful results is always to have an excess of ammonia present.
3. The butyl nitrite is freshly distilled as a general precaution, because a product which has stood for some time is often partially decomposed.
4. It is suggested that gaseous ethyl nitrite be passed in until the precipitate ceases to increase (W. W. Hartman, private communication). However, it is probable that butyl nitrite is more convenient for a laboratory method. A method for the preparation of ethyl nitrite is described in Org. Syn. 10, 22.
5. In the preparation of cupferron, it has been recommended that the butyl nitrite be added all at one time. This procedure is satisfactory only when the amount of phenylhydroxylamine used is less than 200 g.; otherwise the reaction becomes extremely vigorous and an excessive proportion of ether is lost. The directions given above, on the other hand, are adaptable for the preparation of large quantities of cupferron. For the rapid preparation of small quantities of material, the butyl nitrite may be added all at one time, provided sufficient excess of ammonia is present.
6. If ammonia is kept in a definite excess at all times, a rise of temperature to the boiling point of ether appears to do no harm. The lower temperature was used because it makes possible a more rapid addition of the nitrite.
7. It is found that 75 per cent of the ether and 95 per cent of the butyl alcohol used may be recovered, and that one person, working six to seven hours, is able to prepare 800 g. of cupferron. The recovered ether may be used over again, provided the following procedure is observed: The phenylhydroxylamine is dissolved in a little fresh ether, the solution cooled and treated with ammonia, then the recovered ether added. This precaution is necessary owing to the presence of some butyl nitrite in the recovered ether.
8. The addition of a small quantity of acetophenetidide to a solution of cupferron reagent tends to prevent its decomposition.1
Cupferron has been kept in dark bottles sealed with viscose caps for a year without decomposition.
3. Discussion
Nitroso-β-phenylhydroxylamine, of which cupferron is the ammonium salt, can be prepared by the action of sodium nitrite and hydrochloric acid on β-phenylhydroxylamine,2 from a mixture of alkyl nitrite and β-phenylhydroxylamine in the presence of ammonia in ether or benzene solution,3 and by the zinc dust reduction of nitrobenzene in the presence of amyl nitrite and ammonium hydroxide solution.4
This preparation is referenced from:

References and Notes
  1. Germuth, Chemist-Analyst, 17, No. 3, 3; 15 (1928) [C. A. 22, 3372 (1928)].
  2. Wohl, Ber. 27, 1435, 1554 (1894); Bamberger and Landau, Ber. 52, 1839 (1919); Marvel and Kamm, J. Am. Chem. Soc. 41, 280 (1919).
  3. Baudisch, Chem. Ztg. 35, 913 (1911); Baudisch and King, J. Ind. Eng. Chem. 3, 629 (1911); Kasanof, ibid. 12, 799 (1920); Marvel and Kamm, J. Am. Chem. Soc. 41, 280 (1919); Slotta and Jacobi, Z. anal. Chem. 80, 97 (1930); This last method, using ethyl nitrite, is promising but has not been checked completely.
  4. Baudisch, Ger. pat. 227, 659 [Frdl. 10, 126 (1910–12)].

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


ammonium salt


hydrochloric acid (7647-01-0)

ammonium carbonate (506-87-6)

ammonia (7664-41-7)

Benzene (71-43-2)

ether (60-29-7)

sodium chloride (7647-14-5)

sodium nitrite (7632-00-0)

nitrite (14797-65-0)

butyl alcohol (71-36-3)

Nitrobenzene (98-95-3)

Cupferron (135-20-6)

Phenylhydroxylamine (100-65-2)

Butyl nitrite,
n-butyl nitrite (544-16-1)

ethyl nitrite (109-95-5)

acetophenetidide (62-44-2)

amyl nitrite (463-04-7)

ammonium hydroxide (1336-21-6)