Organic Syntheses, Coll. Vol. 8, p.16 (1993); Vol. 67, p.187 (1989).
Wet, 5% rhodium on carbon (1.1 g) (Note 1)
, tetrahydrofuran (200 ml) (Note 2)
, and nitrobenzene (41.0 g) (Note 3)
are introduced into a 500-mL, three-necked, round-bottomed flask
fitted with a mechanical stirrer
, a thermometer
, and a condenser
. The mixture is cooled to 15°C and hydrazine hydrate (17.0 g) (Note 4)
is introduced into the reaction mixture from a pressure-equalized addition funnel
over 30 min. The temperature of the mixture is maintained at 25–30°C throughout the addition by means of an ice–water bath
. After the mixture is stirred for a further 2 hr at 25–30°C, the reaction is complete (Note 5)
. The mixture is filtered and the catalyst washed with a little tetrahydrofuran
. The solution is used immediately in the acylation step (Note 6)
To the N-phenylhydroxylamine
solution in a 1000-mL, three-necked, round-bottomed flask
fitted with a mechanical stirrer
and a thermometer
is added a slurry of sodium bicarbonate (42 g)
in water (40 mL). The mixture is cooled to −4°C in an ice–salt bath
before acetyl chloride (26.0 g) (Note 7)
is introduced into the well-stirred mixture over 1 hr (Note 8)
while the temperature is maintained below 0°C. Stirring is then continued for 30 min before a solution of sodium hydroxide (20.0 g)
in water (200 mL) is added, keeping the temperature below 20°C. The aqueous phase is separated, the tetrahydrofuran
phase is diluted with an equal volume of petroleum ether
, the aqueous phase is separated again, and the organic phase is extracted with aqueous 10% sodium hydroxide solution (2 × 50 mL)
. The combined aqueous phases are washed with methylene chloride (200 mL)
and then neutralized with concentrated hydrochloric acid
(cooling employed). The mixture is extracted with methylene chloride (3 × 100 mL)
and the extracts are combined, dried over magnesium sulfate
, filtered, and concentrated at reduced pressure (about one-fifth volume) (Note 9)
. After the solution is cooled to 40°C, 100 mL of petroleum ether
) is added. The mixture is stirred at 10°C for 39 min before filtering and washing with additional petroleum ether
. The material is dried at room temperature to afford 39.3–40.1 g
) of N-acetyl-N-phenylhydroxylamine
as a white crystalline solid, mp 66–67°C
) (Note 10)
The 5% rhodium on carbon used was purchased dry from Engelhard Industries Ltd.
The checkers purchased it from Aldrich Chemical Company, Inc. The catalyst is used wet (40–50% water) to reduce the risk of fire when the solvent is added.
Tetrahydrofuran was from a bulk supply purchased from Blagden Campbell
. The checkers obtained it from EM Science. The solvent was tested for peroxides prior to use.
Nitrobenzene was supplied by BDH Chemicals Ltd.
, and was used as received. The checkers obtained it from Aldrich Chemical Company, Inc. Nitrobenzene
should be handled only with gloves and in an efficient fume hood.
Hydrazine hydrate was purchased from FBC Industrial Chemicals
and was used as supplied. The checkers obtained it from Aldrich Chemical Company, Inc. Hydrazine
is a severe poison and should be handled only with gloves in an efficient fume hood.
An HPLC system was used to monitor the reduction and to determine the end of the reaction. The HPLC monitoring was not employed by the checker. However, TLC indicated that the reduction was almost complete after stirring for 2 hr at 25–30°C. If only a slight excess (1.03 equiv) of hydrazine
is employed, the reaction is generally complete in 2 hr and excessive overreduction cannot occur.
The HPLC system
consisted of a Waters C18 μ-Bondapak column
, a mobile phase consisting of 15% acetonitrile
, 85% 0.05 M aqueous ammonium acetate
using a flow rate of 2 mL/min and a UV wavelength detector for 235 nm
. The relative response factors of nitrobenzene
were 1.75 and 0.66, respectively.
Acetyl chloride was obtained from Hoechst
and was used as supplied. The checkers obtained it from Fluka Chemical Corporation. The quantity of acetyl chloride
used is 1.05 equiv based on the HPLC yield. (The checkers simply used the amount specified.) Acetyl chloride
should be handled only with gloves in an efficient fume hood.
No vigorous, exothermic reaction is seen during the addition of acetyl chloride
, but the addition should be slow because of the heterogeneous nature of the reaction and the need to destroy efficiently hydrogen chloride
as it is formed. The product, like N-phenylhydroxylamine
, is sensitive to acid and undergoes the Bamberger rearrangement.3
Excessive heating causes decomposition of the product. This method also affords an easily handled crystalline solid of good purity.
The following analytical data have been obtained: 1
H NMR (CDCl3
, 100 MHz) δ: 2.11 (s, 3 H acetylmethyl); 7.40 (m, 5 H, aromatics); 8.90 (board, 0.6 H, NOH); IR (Nujol) cm−1
: 3140, 2930, 2860, 1630, 1595, 1460, 1380. Anal. calcd. for C8
: C, 63.56; H, 6.00; N, 9.27. Found: C, 63.48; H, 5.99; N, 9.21. Nonaqueous titration (Bu4
This preparation illustrates a convenient reduction of nitrobenzene
under catalytic transfer hydrogenation conditions to give N-phenylhydroxylamine
in high yield and demonstrates a monoacylation method to afford the N
-acetyl derivative in high yield. Some work has been done in this area by Johnstone et al.4
A number of other reductive methods described in the literature were tried,5,6,7
but these were not as good as the procedure described here. Phenylhydroxylamine
is thermally unstable, can undergo a Bamberger rearrangement,3
and deteriorates on storage, so its isolation is undesirable. The material was therefore converted directly, without isolation, to its more stable N
-acetyl derivative. Other acylation methods led to mixtures of mono and diacylated products.
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