New synthesis of 4-nintrobenzamide

Article abstract of DOI:10.1023/B:RUJO.0000003187.11780.e4

The reaction of 4-nitrobenzoic acid with ammonia in the presence of various catalysts was studied. Tetrabutoxytitanium and boric acid with addition of PEG-400 favor formation of 4-nitrobenzamide in a high yield. The amidation occurs in the temperature range from 160 to 185°C in trichlorobenzene and in a mixture of trichlorobenzene with o-xylene. Neither PEG-400 nor the above catalysts in the absence of PEG-400 do not catalyze the reaction.

Full text of DOI:10.1023/B:RUJO.0000003187.11780.e4

Russian Journal of Organic Chemistry, Vol. 39, No. 7, 2003, pp. 972 974. Translated from Zhurnal Organicheskoi Khimii, Vol. 39, No. 7, 2003,
pp. 1033 1035.
Original Russian Text Copyright
2003 by Shteinberg.
New Synthesis of 4-Nintrobenzamide
L. Ya. Shteinberg
Institute of Chemical Technology and Industrial Ecology ( Krasitel’ Public Corporation),
pl. Khimikov 3, Rubezhnoe, Luganskaya oblast, 93000 Ukraine
Received April 26, 2002
Abstract The reaction of 4-nitrobenzoic acid with ammonia in the presence of various catalysts was studied.
Tetrabutoxytitanium and boric acid with addition of PEG-400 favor formation of 4-nitrobenzamide in a high
yield. The amidation occurs in the temperature range from 160 to 185 C in trichlorobenzene and in a mixture
of trichlorobenzene with o-xylene. Neither PEG-400 nor the above catalysts in the absence of PEG-400 do not
catalyze the reaction.
We previously showed that titanium, phosphorus,
and tin compounds catalyze acylation of aromatic
amines with aromatic carboxylic acids. Conditions
were found for the preparation of N-arylbenzamides,
2,3-hydroxynaphthanilide, 1-benzoylaminoanthra-
quinone, and 2-arylbenzimidazoles in high yields
[1 4]. In the present work we examined catalytic
reaction of 4-nitrobenzoic acid with ammonia.
Taking into account that ammonium salts of sub-
stituted benzoic acids are poorly soluble in weakly
polar solvents which are usually used in the catalytic
acylation of substituted anilines [1 3], as reaction
medium we selected more polar o-dichlorobenzene
and trichlorobenzene. In some experiments, toluene
or o-xylene was added to facilitate removal of the
liberated water.
The reaction of 4-nitrobenzoic acid with ammonia
was studied in the temperature range from 160 to
185 C in the presence of various catalysts. Ammonia
was taken in a stoichiometric amount (as ammonium
4-nitrobenzoate) or was bubbled through the reaction
mixture (in excess) throughout the process (5 10 h).
Under the above conditions, none of the catalysts
listed below turned out to be effective: Ti(OBu)4,
SnCl4, H3BO3, H3PO3, H3PO4, (CH3O)2P(O)H,
FeSO4 7H2O. Almost no 4-nitrobenzamide was
obtained.
We have found that addition of PEG-400 as co-
catalyst considerably enhances the catalytic activity.
By bubbling gaseous ammonia through a solution of
4-nitrobenzoic acid in the presence of a catalyst and
PEG-400, 4-nitrobezamide was formed in high yield
(see table).
When PEG-400 was added to the reaction mixture
containing ammonium 4-nitrobenzoate without
bubbling ammonia, 4-nitrobenzamide was not formed.
By special experiments, using the catalytic system
boric acid PEG-400, we showed that trichlorobenzene
does not react with ammonia and that 4-nitrobenz-
amide is not converted into 4-aminobenzamide or
N-(4-nitrobenzoyl)-4-nitrobenzamide.
As follows from the data in table, in the presence
of PEG-400, effective catalysts are tetrabutoxytita-
nium (run nos. 1, 2), boric acid (run nos. 3, 4), and
dimethyl hydrogen phosphite (run no. 5). Iron(II) sul-
fate and tin(IV) chloride showed no catalytic activity
(run nos. 6, 7). The latter catalysts promoted forma-
tion in a low yield of compounds other than 4-nitro-
benzamide. PEG-400 did not exhibit catalytic activity
in the absence of other catalyst (run no. 8).
It should be emphasized that 4-nitrobenzamide is
formed in a high yield in the presence of various
amounts of a catalyst and PEG-400 (cf. run nos. 1 4);
therefore, there exists the possibility for further
optimization of the reaction conditions.
According to the results of run nos. 1 and 2,
vigorous boiling of the mixture and removal of water
as azeotrope are not necessary for the reaction to be
successful, in contrast to the data of [2]. Presumably,
the liberated water can also leave the reaction mixture
1070-4280/03/3907-0972$25.00 2003 MAIK Nauka/Interperiodica

NEW SYNTHESIS OF 4-NINTROBENZAMIDE
Reaction conditions
973
Synthesis of 4-nitrobenzamide
Run
Yield of
4-nitrobenz-
amide, %
no.
tempera- reaction
catalyst, mol %a
PEG-400, mol %a
0.9
solvent
ture,
C
time, h
1
Ti(OBu)4, 2.0
Trichlorobenzene
170 175
6
10
5
60
90
74
59
92
64
35
2
3
4
16
17
2
3
Ti(OBu)4, 0.9
H3BO3, 7.0
22.0
16.0
Trichlorobenzene
Trichlorobenzene o-xylene
180 185
160 165
5
10
4
9
6
6
6
7
7
4
5
6
H3BO3, 34.0
54.0
18.0
15.0
35.0
10.0
0.9
Trichlorobenzene o-xylene
Trichlorobenzene o-xylene
o-Dichlorobenzene toluene
o-Dichlorobenzene toluene
Trichlorobenzene o-xylene
Trichlorobenzene
160 165
180 183
160 165
160 165
160 165
170 175
170 175
(CH3O)2P(O)H, 3.0
FeSO4 7H2O, 3.0
SnCl4, 7.0
7
8
9
10
H3PO4, 2.0
H3PO3, 2.0
0.9
Trichlorobenzene
with a stream of ammonia. It is also probable that,
even without removal of water, a large excess of
ammonia bubbled through the mixture shifts the
equilibrium toward formation of 4-nitrobenzamide
which is thus obtained in high yield.
The role of PEG-400 in the process under study
remains unclear, though this compound is known as
an efficient phase-transfer catalyst [5]. It may be seen
that PEG-400 favors dissolution of boric acid and
hence homogenization of the reaction mixture. On the
other hand, the other efficient catalyst, tetrabutoxy-
titanium, is readily soluble in trichlorobenzene in the
absence of PEG-400.
Thus, catalytic systems have been proposed (tetra-
butoxytitanium PEG-400 and boric acid PEG-400)
which ensure direct synthesis of 4-nitrobenzamide.
The procedure is advantageous, for it does not involve
carbonyl chloride or thionyl chloride (for preliminary
conversion of 4-nitrobenzoic acid into 4-nitrobenzoyl
chloride.
plates using binary mixtures acetone hexane and
acetone chloroform as eluent; spots were visualized
with UV light.
Synthesis of 4-nitrobenzamide. A mixture of
2.5 g (14.9 mmol) of 4-nitrobenzoic acid, 45 ml of
appropriate solvent, catalyst, and PEG-400 was heated
for 0.5 h at 160 185 C in a flask equipped with
a thermometer, stirrer, gas-inlet tube, Dean Stark trap,
and reflux condenser while bubbling ammonia at
a flow rate of 500 ml/h. When o-dichlorobenzene or
trichlorobenzene was used as solvent, the Dean Stark
trap was initially empty. When the reaction was
carried out in binary mixtures containing toluene or
o-xylene (5 ml) as the second component, the Dean
Stark trap was filled with that solvent.
When the reaction was complete, the mixture was
cooled to room temperature, and the precipitate was
filtered off, washed with 20 ml of a 10 15% aqueous
solution of ammonia and with 20 ml of water, and
dried. The product had mp 196 197 C [7]. The results
of experiments are summarized in table.
EXPERIMENTAL
4-Nitrobenzamide was synthesized from ammo-
nium 4-nitrobenzoate following the same procedure,
but no ammonia was bubbled through the mixture.
The solvent was a mixture of trichlorobenzene and
o-xylene, ammonium 4-nitrobenzoate H3BO3
PEG-400 molar ratio 1:0.07:0.16, reaction time 10 h,
temperature 160 165 C.
4-Nitrobenzoic acid, Ti(OBu)4, SnCl4, H3BO3,
H3PO3, H3PO4, (CH3O)2P(O)H, o-xylene, toluene,
and trichlorobenzene were purified as described in
[2, 3, 6]. Iron(II) sulfate heptahydrate FeSO4 7H2O
of pure grade was used without preliminary purifica-
tion, and o-dichlorobenzene was purified by vacuum
distillation.
Ammonium 4-nitrobenzoate. 4-Nitrobenzoic acid,
4.0 g (20.5 mmol), was dispersed in 20 ml of 25%
aqueous ammonia. The mixture was stirred and dried
The reaction mixtures and products were analyzed
by thin-layer chromatography on Silufol UV-254
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 7 2003

974
SHTEINBERG
at 60 80 C until a colorless solid, ammonium 4-nitro-
benzoate, precipitated.
3. Shteinberg, L.Ya., Kondratov, S.A., and Shein, S.M.,
Zh. Org. Khim., 1989, vol. 25, p. 1945.
The reactions of 4-nitrobenzoic acid with 4-nitro-
benzamide and of 4-nitrobenzamide with ammonia
were carried out in trichlorobenzene at 180 185 C
(reaction time 6 h); 4-nitrobenzoic acid 4-nitrobenz-
amide H3BO3 PEG-400 molar ratios 1:1:0.07:0.16
and 0:1:0.07:0.16, respectively.
4. Kondratov, S.A., Shteinberg, L.Ya., Shein, S.M.,
Udovichenko, L.V., and Boiko, V.D., Zh. Org. Khim.,
1994, vol. 30, p. 284.
5. Gol’dberg, Yu.Sh., Izbrannye glavy mezhfaznogo
kataliza (Selected Topics in Phase-Transfer Catalysis),
Riga: Zinatne, 1989, p. 554.
6. Shteinberg, L.Ya., Boiko, V.D., Kondratov, S.A.,
Shein, S.M., and Shteinberg, Ya.B., Zh. Org. Khim.,
1992, vol. 28, p. 1034.
REFERENCES
1. Kondratov, S.A., Shteinberg, L.Ya., Boiko, V.D., and
Shein, S.M., Zh. Org. Khim., 1986, vol. 22, p. 2466.
7. Laptev, N.G. and Vysokosova, A.I., USSR Inventor’s
Certificate no. 127657, 1960; Byull. Izobret., 1960,
no. 8.
2. Shteinberg, L.Ya., Kondratov, S.A., and Shein, S.M.,
Zh. Org. Khim., 1988, vol. 22, p. 1968.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 7 2003