Nitration of 4-acetylamino-4′-nitro-, 4-acetylamino-2′ -nitrodiphenyl sulfides and 4-acetylamino-2′-nitrodiphenyl ether

Article abstract of DOI:10.1023/A:1020391104880

Nitration of 4-acetylamino-4′-nitrodiphenyl sulfide, 4-acetylamino-2′-nitrodiphenyl sulfide, and 4-acetylamino-2′ -nitrodiphenyl ether yields respectively 4-acetylamino-3,4′ -dinitrodiphenyl sulfide, 4-acetylamino-2′,3-dinitrodiphenyl sulfide, and 4-acety

Full text of DOI:10.1023/A:1020391104880

Russian Journal of Organic Chemistry, Vol. 38, No. 6, 2002, pp. 833 839. Translated from Zhurnal Organicheskoi Khimii, Vol. 38, No. 6, 2002,
pp. 875 882.
Original Russian Text Copyright
2002 by Pilyugin, Mikhailyuk, Kosareva, Kiseleva.
Nitration of 4-Acetylamino-4 -nitro-,
-Acetylamino-2 -nitrodiphenyl Sulfides
4
and 4-Acetylamino-2 -nitrodiphenyl Ether
V. S. Pilyugin, A. N. Mikhailyuk, V. M. Kosareva, and G. V. Kiseleva
Technological Research Institute of Herbicides and Plant Growth Regulator, Academy of Sciences of Bashkortostan
Republic, Ufa, 450029 Russia
Received February 23, 2001
Abstract Nitration of 4-acetylamino-4 -nitrodiphenyl sulfide, 4-acetylamino-2 -nitrodiphenyl sulfide, and
4
4
-acetylamino-2 -nitrodiphenyl ether yields respectively 4-acetylamino-3,4 -dinitrodiphenyl sulfide,
-acetylamino-2 ,3-dinitrodiphenyl sulfide, and 4-acetylamino-2 ,3-dinitrodiphenyl ether.
4
-Acetylamino-4 -nitrodiphenyl sulfide (I), 4-acet-
ylamino-2 -nitrodiphenyl sulfide (II), 4-acetylamino-
-nitrodiphenyl ether (III), and obtained therefrom
OC H NO . Therefore the direction of nitration may
6 4 2
be predicted by analysis of the electronic effects of
these substituents [6].
2
by nitration respectively 4-acetylamino-3,4 -dinitro-
diphenyl sulfide (IV), 4-acetylamino-2 ,3-dinitrodi-
phenyl sulfide (V), and 4-acetylamino-2 ,3-dinitro-
diphenyl ether (VI) are important semiproducts in the
synthesis of quite a number of helminthicides from
the series of 2-aminobenzimidazole derivatives [1 3].
The demand on these preparations is fairly high, and
therefore the development of reliable synthetic
methods for them is urgent.
The groups SC H NO in compounds I and II and
6
4
2
OC H NO in substrate III possess overall negative
6
4
2
effects ( I and E) and decrease the electron density
in the second benzene ring impeding its nitration and
orienting the new substituent into the meta-position
with respect to these groups. On the other hand, the
MeC(O)NH group possesses an electropositive effect
and directs the nitro group entering into this ring
into ortho- and para-positions.
The present study was aimed at investigation of
compounds I III nitration to obtain the correspond-
ing dinitro derivatives IV VI and to optimize the
nitration conditions.
Therefore obviously in this case occurs correlated
orientation, and it is possible to expect selective
formation from compounds I III respective dinitro
derivatives IV VI.
The nitration mechanism in the aromatic series is
considered in detail in numerous publications [4 8].
In the molecules of substrates I III in para-posi-
tion with respect to each other are present two groups
capable to affect the orientation of nitration:
MeC(O)NH and SC H NO , MeC(O)NH and
6
4
2
Nitrocompound IV was obtained in [9] by nitration
of sulfide I by the mixture of acetic and nitric acids.
3
The nitric acid used was of density 1.4 g cm .
Regretfully, the yield of the product was not indicated,
but it was stated that the reaction is accompanied by
1
070-4280/01/3806-833$27.00 2002 MAIK Nauka/Interperiodica

8
34
PILYUGIN et al.
oxidation of compound IV into sulfoxide and sulfone.
Under more stringent conditions, when nitration was
performed with the use of a mixture of equal volumes
of nitric and sulfuric acids, sulfone was the main
reaction product.
the nitration of 4-acetylamino-4 nitrodiphenyl sulfide
proceeds through N-nitro compound that under mild
conditions is the main reaction product.
To support the assumed mechanism of nitration of
4
-acetylamino-4 -nitrodiphenyl sulfide we attempted
The highest yield of dinitrosulfide IV (45%) we
to nitrate 4-(N-dimethylamino)-4 -nitrodiphenyl
obtained at nitrating with dilute nitric acid ( 1.35 g
sulfide in the mixture of acetic acid with chloroform
3
3
cm ) and at the ratio substrate HNO AcOH 1: 3:
by dilute nitric acid ( 1.35 g cm ) for 6 h at 18
3
1
0. The nitric acid was added to the dispersion of the
20 C. The analysis of the reaction mixture showed
that no nitration occurred. 4-(N-dimethylamino)-4 -
nitrodiphenyl sulfide was prepared by methylation
of 4-amino-4 -nitrodiphenyl sulfide with dimethyl
sulfate in a water-dioxane mixture in the presence
initial compound I in AcOH at room temperature, and
then the reaction mixture was heated to 35 40 C for
3
4 h. In the course of the process a liberation of
nitrogen oxides as brown vapor was observed. The
addition of small amount of urea did not prevent
oxidation, and at large quantities of urea the nitration
decelerated up to total inhibition of reaction when
of NaHCO [13] and analyzed by NMR and HPLC
3
methods.
The rearrangement of N-nitro compound into a
C-nitro compound we succeeded to perform by
boiling the reaction mixture in acetic acid or by stir-
ring at room temperature in acetic acid with addition
of sulfuric acid. In a mixture of acetic and nitric acid
the rearrangement required a moderate heating. This
rearrangement was accompanied by appearance of
oxidation products, and their amount is greater in the
presence of nitric acid.
1
mole of urea per 1 mole of substrate I was used.
The data obtained support the mechanism of nitra-
tion with dilute nitric acid [10] as catalytic nitra-
tion , and the process in the dilute nitric acid
proceeds only in the presence of nitrogen(IV) oxides.
The side oxidative processes result in increasing
concentration of nitrogen(IV) oxides in the course of
nitration. The molecules of nitric acid here serve as a
source of nitrogen dioxide.
Therefore after adding the mixture of nitric and
acetic acids the reaction mixture was stirred for 1 h at
Nitrogen oxides play dual role in nitration of
sulfide I. On the one hand, no nitration occurs when
they are absent; on the other hand, they oxidize sulfur
in sulfide I into sulfoxide and sulfone. We observed
that if the reaction mixture was not stirred, the
removal of excessive nitrogen oxides was hampered,
and the oxidative processes increased.
15 25 C, and then gradually into the reaction mixture
was added separately prepared mixture of sulfuric and
acetic acid in a definite required ratio. Then the
reaction mixture was vigorously stirred at 15 25 C
for 4 5 h more.
On completion of nitration into the reaction mix-
ture water was added in amount necessary for separat-
ing acids from the solvent. After layers separation
the organic layer was twice washed with hot water.
To a solution obtained of compound IV in the chloro-
form acetic acid mixture was added water, and the
main part of solvents was distilled off in a vacuum.
The dispersion of dinitrosulfide IV thus obtained was
filtered, the product was washed on the filter with
2-propanol, water, and dried. The results of com-
pound I nitration in the mixture of chloroform and
acetic acid are listed in Table 1.
To reduce the excess of nitrogen(IV) oxides and
therewith the oxidation processes the nitration of
sulfide I should be performed in less polar medium
that acetic acid. Therefore we carried out the nitration
in mixtures of acetic acid with aprotic solvents for
instance, with dichloromethane, dichloroethane,
chloroform, chlorobenzene etc. The nitration was
performed in a mixture of acetic acid with chloroform
3
(
1: 3 by volume) using nitric acid of 1.35 g cm .
This procedure resulted in decreased oxidation and
increased yield of dinitrosulfide IV up to 60%.
Thus from the data obtained for nitration of sulfide
I the following conclusions may be drawn. Firstly,
the limiting stage of sulfide IV formation is obviously
the rearrangement of N-nitrocompound into C-nitro-
compound. Secondly, the side oxidation processes
occur at the rearrangement stage or after. Thirdly, in
the presence of sulfuric acid the rearrangement
proceeds under milder conditions and with less oxid-
ation.
In 2 3 h after adding nitric acid in the reaction
mixture were no found either initial compound I and
its oxidation products (according to the data of TLC
and HPL chromatography). However the isolated reac-
tion product had lower melting point that 4-acetyl-
amino-3,4 -dinitrodiphenyl sulfide [9]. Some differ-
ence was also observed in the IR and NMR spectra
of the compound. We presume that similar to [11, 12]
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 6 2002

NITRATION OF 4-ACETYLAMINO-4 -NITRO-...
835
Table 1. Nitration of 4-acetylamino-4 -nitrodiphenyl sulfide (I) in a mixture of chloroform with acetic acid by 57%
nitric acid
Ratios of reagents
Dinitrosulfide (IV)
c
a
a
a
b
yield, %
(I): HNO3
CH COOH: HNO
HNO : H SO
CHCl : (I)
3
3
3
2
4
3
d
e
1
1
1
1
1
1
1
1
1
1
1
1
1
.0: 3.46
.0: 6.97
.0: 6.93
.0: 6.97
.0: 6.00
.0: 1.29
.0: 1.30
.0: 1.30
.0: 1.30
.0: 1.58
.0: 1.60
.0: 1.40
.0: 1.23
4.38: 1.0
2.38: 1.0
2.40: 1.0
2.40: 1.0
2.77: 1.0
8.58: 1.0
9.00: 1.0
9.00: 1.0
8.58: 1.0
8.58: 1.0
8.50: 1.0
9.00: 1.0
8.77: 1.0
21 (93)
20 (93)
55 (72)
56 (75)
56 (76)
56 (92)
58 (93)
58 (94)
57 (93)
69 (91)
70 (92)
69 (92)
46 (89)
33.9: 1.0
22.5: 1.0
33.9: 1.0
29.2: 1.0
1.32: 1.0
1.32: 1.0
1.32: 1.0
1.32: 1.0
1.32: 1.0
1.32: 1.0
1.30: 1.0
1.94: 1.0
3.46: 1.0
3.46: 1.0
3.46: 1.0
3.00: 1.0
3.00: 1.0
3.00: 1.0
3.00: 1.0
3.00: 1.0
3.00: 1.0
3.00: 1.0
3.00: 1.0
3.00: 1.0
a
b
c
d
e
Molar reagents ratio.
Weight ratio.
Yield of crude reaction product (IV); the content of the main product in the sample, wt%, is given in parentheses.
Without acetic acid.
Without solvent.
The latter conclusion seems to contradict the data
9] on sulfone formation as the main product in the
this substance cannot be nitrated under the given
reaction conditions.
[
nitration process with the use of sulfuric acid in the
nitrating system. However in [9] were used con-
centrated nitric and sulfuric acids, and in this case the
nitration apparently occurred by an other mechanism.
The formation of sulfoxide derivative VII is also
unwelcome because it impedes the isolation of the
target dinitro compound IV at the stage of nitration.
Since the source of excess nitrogen oxides was the
nitric acid, we further decreased its amount in the
reaction mixture. At the ratio initial sulfide I nitric
To elucidate the effect of sulfuric acid on the
nitration with a dilute nitric acid we carried out a
series of experiments and established that at the ratio
3
acid ( 1.35 g cm ) acetic acid sulfuric acid
1
: (1.3 1.5): 5: 1.0, providing the sulfuric acid was
3
initial sulfide I nitric acid ( 1.35 g cm ) acetic
added after the nitric acid, we carried out the reaction
at room temperature and increased the yield of the
target dinitro compounds IV to 50%. If the reaction
is carried out in a less polar medium, i.e. in the
mixture of acetic acid with chloroform, then the yield
of compound IV can be raised to 70%.
acid sulfuric acid 1: 3: 5: 0.5, providing the sulfuric
acid be added after the nitric acid, then the nitration
occurred with high rate, the rearrangement did not
require heating, and the whole process could be
carried out at room temperature. However in this case
the content of oxidation products did not decrease.
Thus the optimal parameters of the process are as
follow: the temperature of the main process 15 25 C,
the temperature to the end of the process 20 25 C,
stirring of reaction mixture after nitric acid addition
till the start of sulfuric acid addition for 60 min, the
duration of the process after addition of all acids
If at the same ratio of reagents the sulfuric acid is
added before the nitric acid, then arises a significant
amount of compound originating from oxidation of
the initial sulfide at the sulfur atom (compound VII);
4
5 h, weight ratio of chloroform and acetic acid in
the solvent (3.14 5.24): 1, weight ratio chloroform
substrate I (2.0 3.1): 1, molar ratio nitric acid
sulfide I 1.30: 1.00, the volume ratio of nitric and
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 6 2002

8
36
PILYUGIN et al.
Table 2. Nitration of 4-acetylamino-2 -nitrodiphenyl sulfide (II) in a mixture of chloroform with acetic acid by 57%
nitric acid
Ratios
Yield of crude
c
a
b
b
producta, %
CHCl : CH COOH
Sulfide II: HNO3
H SO : HNO
2 4 3
3
3
2
2
3
3
3
3
3
.00: 1.0
.50: 1.0
.00: 1.0
.33: 1.0
.33: 1.0
.96: 1.0
.96: 1.0
1.0: 2.90
1.0: 2.90
1.0: 2.90
1.0: 2.86
1.0: 2.86
1.0: 2.44
1.0: 2.44
1.0: 65.00
1.0: 65.00
1.0: 65.00
1.0: 64.96
1.0: 64.96
1.0: 49.27
1.0: 49.27
60 (92)
62 (93)
72 (96)
73 (98)
73 (99)
67 (95)
67 (94)
a
b
c
Volume ratio.
Molar ratio of reagents.
Yield of unpurified reaction product V; the content of the main product in the sample, wt%, is given in parentheses.
Table 3. Nitration of 4-acetylamino-2 -nitrodiphenyl sulfide (II) in a mixture of chlorobenzene with acetic acid by 57%
nitric acid
Ratios
Yield of crude
product, %
c
b
b
b
chlorobenzene: acetic sulfide II: HNO3
H SO : HNO
CH COOH: HNO
2
4
3
3
3
a
acid
4
7
3
2
2
2
1
1
.48: 1.0
.27: 1.0
.96: 1.0
.00: 1.0
.00: 1.0
.00: 1.0
.00: 1.5
.00: 1.5
1.0: 2.6
1.0: 2.6
1.0: 4.0
1.0: 2.5
1.0: 2.4
1.0: 2.6
1.0: 2.6
1.0: 2.0
1.0: 40.0
1.0: 40.0
1.0: 40.0
1.0: 60.0
1.0: 65.0
1.0: 60.0
1.0: 60.0
1.0: 60.0
1.0: 1.76
1.0: 1.56
1.0: 1.36
1.0: 1.35
1.0: 1.35
1.0: 1.35
1.0: 0.75
1.0: 0.70
54 (93)
51 (94)
55 (94)
56 (94)
56 (95)
55 (95)
54 (95)
54 (93)
a
b
c
Volume ratio.
Molar ratio of reagents.
Yield of unpurified reaction product V; the content of the main product in the sample, wt%, is given in parentheses.
acetic acids in the nitrating mixture 2.0 : 1.0, the
volume ratio of sulfuric and acetic acids 1.0 : 2.0, the
molar ratio of nitric and sulfuric acids 1.3 : 1.0,
weight concentration of the initial nitric acid 57%
In these experiments into a solution of sulfide II in
the mixed solvent was added a mixture of acetic and
sulfuric acids. Then into the reactor at temperature
not exceeding 30 C was gradually added the nitric
3
(
free of oxides).
acid ( 1.35 g cm ). After the end of nitric acid
addition the reaction mixture was vigorously stirred
for 4 5 h. After completion of the process the separa-
tion of the acid layer and isolation of dinitrosulfide V
from the organic layer was carried out similarly to the
workup described for dinitrosulfide IV.
The nitration of sulfide II differs from that of
sulfide I because the nitro group in ortho-position
with respect to sulfur hampers sulfur oxidation into
sulfoxide and sulfone apparently due to steric
hindrances. This fact simplifies the nitration. The
nitration is also performed with dilute nitric acid.
In Table 2 are given the data on the nitration of
sulfide II in the mixture of chloroform and acetic
acid. The optimal parameters of dinitrosulfide V
synthesis are as follows: reaction temperature of the
The nitration of sulfide II was studied using as
solvent mixtures of acetic acid with chloroform or
chlorobenzene.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 6 2002

NITRATION OF 4-ACETYLAMINO-4 -NITRO-...
837
Table 4. Nitration of 4-acetylamino-2 -nitrodiphenyl ether III with 90% nitric acid at 40 45 C
Ratios
Concentration of
Duration of
process, h
Yield of crude
c
product, %
ether III:
HNO3
acetic acid:
HNO :acetic
anhydride
nitric acid %
3
a
a
a
HNO3
1.0: 3.12
1.0: 3.12
1.0: 3.10
1.0: 3.00
1.0: 3.01
1.0: 2.94
1.0: 2.87
1.0: 2.75
1.0: 2.74
1.0: 2.74
1.0: 2.74
1.0: 2.77
1.0: 2.70
1.0: 2.70
1.0: 2.68
1.0: 2.65
1.0: 2.65
1.0: 2.65
1.0: 2.64
1.0: 2.64
1.0: 3.11
1.0: 3.11
1.0: 2.09
1.0: 4.94
1.0: 2.77
1.0: 4.73
1.0: 5.13
1.0: 5.11
1.0: 5.11
1.0: 5.11
1.0: 5.11
1.0: 5.12
1.0: 5.13
1.0: 5.13
1.0: 2.12
1.0: 2.12
1.0: 2.12
1.0: 2.13
1.0: 2.12
1.0: 2.12
1.0: 2.35
1.0: 2.35
1.0: 2.04
1.0: 2.65
1.0: 2.65
1.0: 0.34
1.0: 0.37
1.0: 0.37
1.0: 0.36
1.0: 0.36
1.0: 0.36
1.0: 0.36
1.0: 0.37
1.0: 0.37
1.0: 2.10
1.0: 1.77
1.0: 1.77
1.0: 1.77
1.0: 2.09
1.0: 1.76
57
57
57
57
57
90
90
90
90
90
90
90
90
90
57
57
57
57
57
57
5.0
5.5
7.0
8.0
9.0
3
1.0
1.5
1.0
1.5
2.0
1.75
1.5
1.5
7.0
4.5
5.5
6.5
7.0
6.5
92 (97)
92 (96)
84 (91)
76 (99)
75 (99)
90 (99)
93 (97)
94 (98)
79 (98)
93 (99)
95 (99)
93 (99)
92 (98)
92 (98)
85 (99)
96 (96)
95 (97)
95 (98)
86 (99)
85 (98)
a
b
c
Molar ratio of reagents.
Yield of crude dinitroether VI, wt% of main compound in the samples is given in parentheses.
Nitration temperature 32 C.
main process 25 30 C, temperature to the end of the
process 30 35 C, temperature during evaporation of
chloroform in a vacuum not higher than 45 C, dura-
tion of the process 5 6 h, molar ratio initial sulfide
II nitric acid 1.0 : (2.6 2.9), molar ratio nitric acid
(2.0 4.0): 1.0, molar ratio initial sulfide II nitric
acid 1.0 : (2.4 2.6), molar ratio nitric acid sulfuric
acid (60 65): 1.0, molar ratio acetic acid nitric acid
1.00: 1.35, the process temperature and duration are
the same as in nitration of sulfide II in the mixture of
chloroform and acetic acid.
sulfuric
acid
(50 65): 1.0,
volume
ratio
chloroform acetic acid in the solvent (3.0 4.0):1.
Our investigation showed that nitration of ether III
was best performed by concentrated nitric acid (90%)
in a mixture of acetic acid and acetic anhydride. Into
a reactor was charged the necessary amount of acetic
acid, and at stirring ether III of technical grade. Into
the mixture was poured acetic anhydride, and then at
vigorous stirring and cooling with brine to 10 15 C
into the reactor is gradually charged the concn. nitric
acid. On completion the nitric acid addition the reac-
tion mixture is stirred at 20 25 C for 20 25 min, and
then at 40 45 C the vigorous stirring was continued
for 4 6 h more.
In nitration carried out in a mixture of chloro-
benzene and acetic acid the yield and quality of the
target product V are somewhat worse than in reaction
performed in a mixture of chloroform and acetic acid.
In this case after the end of nitration and washing
of the reaction mixture from oxides and acids the
solution of compound V in chlorobenzene was cooled
with brine to 0 5 C, filtered, the product on filter
was washed with 2-propanol and water, and dried.
The results obtained at nitration of sulfide II in
the mixture of acetic acid with chlorobenzene are
presented in Table 3.
The results obtained at nitration of ether III in
the mixture of acetic acid and acetic anhydride are
presented in Table 4.
The best parameters of the process are as follows:
volume ratio chlorobenzene acetic acid in the solvent
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 6 2002

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38
PILYUGIN et al.
The analysis of data obtained shows that nitration
Analysis of sulfide II and dinitrosulfide V was
performed by separation of these compounds on a
column with reversed phase Bondapac C18 using the
following eluent system: 33.5% (by volume) of
acetonitrile, 54.5% of water, 12% of 2-propanol, and
5 ml of acetic acid added per 0.5 l of eluent. The
calculation of chromatograms was done by the
method of internal normalization of peaks area.
of ether III occurs more readily than that of sulfide
II: the yield and quality of dinitroether VI are
higher. Therewith the parameters of the process may
be varied within relatively wide limits without
hampering its outcome.
As optimal parameters of ether III nitration may
be recommended the following: temperature 40
4
5 C, duration 4.5 6.5 h, 90% nitric acid, molar
Analysis of ether III and dinitroether V was per-
formed by separation of these compounds on a
column with reversed phase Rsil or Ultrasphere ODS
using the following eluent system: 65% (by volume)
of methanol, 35% of water, with addition 25 ml of
solution of 18-crown-6 in methanol (0.1 g per 1 ml of
methanol) per 1 l of eluent. The calculation of
chromatograms was done by the method of internal
normalization of peaks area.
ratio initial ether III nitric acid 1.0 : (2.7 2.9), molar
ratio nitric acid acetic acid 1.0 : (2.1 5.1), molar
ratio nitric acid acetic anhydride 1.0 : (0.3 1.7).
EXPERIMENTAL
Reaction mixtures and crude nitration products in
the process of preparation of dinitro derivatives IV,
V, and VI were analyzed by TLC (qualitatively) and
HPLC (quantitatively), and identification of products
To a dispersion of 172.8 g (0.6 mol) of sulfide I
in 350 ml of chloroform at 20 25 c was added 105 ml
of acetic acid (11.3 g, 1.76 mol), and dropwise was
added 73.7 ml (99.47 g, 0.9 mol) of nitric acid (
1
3
was performed by IR and C NMR spectroscopy.
IR spectra of compounds were measured on
spectrometer Jasco 810-IR in the range 4000
3
1
1.35 g cm , 57%). In 60 min after addition of nitric
4
00 cm from solutions in CCl or mulls in mineral
4
1
3
acid was added dropwise while stirring at room
temperature a solution of 36 ml (67 g; 0.69 mol) of
concn. sulfuric acid in 72 ml(76.32g, 1.2 mol) of
acetic acid, and the stirring was continued for 5 h
more.
oil. C NMR spectra were registered on spectrometer
Bruker CXP-100 in FT mode at operating frequency
2
2.63 MHz at full decoupling from protons or with-
out decoupling, solvent DMSO, reference HMDS.
The assignment of signals was based on chemical
shifts, coupling constants, multiplicity of signals,
and the intensity ratio of peaks. In interpretation of
spectra were used data on chemical shifts of model
compounds and calculations of magnetic shielding in
aromatic ring.
In the course of nitration the reaction progress was
monitored by sampling every hour and analysis by
TLC for the presence of initial sulfide I. If the initial
sulfide was still detected, to the reaction mixture was
added a supplementary amount of nitric and sulfuric
acids (in a mixture with acetic acid). After stirring for
TLC analyses were carried out on Silufol plates
with thin layer of silica gel, spots visualized by solu-
tion of tin dichloride, diazotization of the anilines
formed, and their azocoupling with -naphthol.
Eluent benzene ethanol, 10: 1.
1
h the reaction mixture was again analyzed for the
presence of initial sulfide I. At the absence of sulfide
I in the probe the nitration was finished.
After the end of nitration into the reactor 500 ml
of water was added for washing out acids from the
solution. The mixture was vigorously stirred, after
separation the acid water layer was removed, and the
organic layer was washed twice more with hot water.
Then to the organic solution was added 500 ml of
water, and the solvents were distilled off in a vacuum
(at residual pressure about 100 mm Hg and at
temperature not higher than 45 C). The residue was
poured into a crystallization dish with cold water and
after stirring was filtered. The precipitate on filter
was thoroughly washed with 2-propanol and water,
and dried. We obtained 139.86 g (about 70%) of
4-acetylamino-3,4 -dinitrodiphenyl sulfide IV, mp
HPLC analyses were performed on Altex model
30 isocratic chromatograph, pump 110, UV detector
53, loop feeders 210 of 20 l volume, Hamilton
3
1
microsyringes of SNR type, volumes 30, 50, or
1
00 l.
The separation and analysis of sulfide I and di-
nitrosulfide IV was carried out on a stainless steel
column 250 4.6 mm with reversed phase Ultra-
sphere ODS, particle size 5 . Analysis and identific-
ation of products obtained by nitration of sulfide I
was performed in the following eluent system: 20
3
0% water (by volume), 70 80% of acetonitrile,
internal reference diphenyl.
140 141 C (publ. mp 140 C [9]). R of the initial
f
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 6 2002

NITRATION OF 4-ACETYLAMINO-4 -NITRO-...
839
product 0.39, of the final product 0.60 (eluent
benzene ethanol, 10: 1).
4-Amino-4 -nitrodiphenyl sulfide was methylated
with dimethyl sulfate at 35 C within 3 h by procedure
[
13].
In nitration of 4-acetylamino-2 -nitrodiphenyl
sulfide (II) 172.8 g (0.6 mol) of the sulfide was dis-
solved in a mixture of 350 ml of chloroform (or
chlorobenzene) and 105 ml (111.3 g; 1.76 mol) of
acetic acid. Into the reactor at cooling and stirring
was charged a mixture of 72 ml (76.32 g, 1.2 mol)
of acetic acid and 36 ml (0.69 mol) of concn. sulfuric
acid. At vigorous stirring (with a high-speed agitator
or even better, with an internal hydroacoustic device)
REFERENCES
1. Kosareva, V.M., Solonenko I.G., Valitov R.B., Pi-
,
lyugin, V.S., Vorob eva, T.P., Mikhailyuk, A.N.,
,
Novik, T.S., Sorokina, O.N., and Belen kii, L.I.,
,
USSR Inventor s Certificate 1246563, 1986; SSSR
Byull. Izobr., 1986.
2
3
4
. Khomutov, M.A., Mikhailyuk, A.N., Belen’kii, L I.,
into the reactor was gradually added dropwise 73.7ml
Novik, T.S., Berezkina, S.V., Pilyugin, V.S., Vali-
3
,
(
99.47 g, 0.9 mol) of nitric acid ( 1.35 g cm ,
tov, R.B., and Demidov, N.V., USSR Inventor s
5
7%) maintaining the temperature below 30 C. After
Certificate 1340073, 1987; SSSR Byull. Izobr., 1987,
no. 35.
. Sorokina, O.N., Kosareva, V.M., Mikhailyuk, A.N.,
Chukina, S.I., Novik, T.S., Berezkina, S.V., Vol-
the nitric acid was added the reaction mixture was
vigorously stirred for 4 5 h. In the course of nitration
the reaction progress was monitored by sampling
every hour and analysis by TLC for the presence of
initial sulfide II. If the initial sulfide was still detected
after 4 5 h of reaction, to the reaction mixture was
added a supplementary amount of nitric acid, and the
temperature was raised to 35 C; the reaction mixture
at this temperature was stirred for 1/0 1.5 h more.
kova, G.N., Pilyugin, V.S., and Valitov, R.B.,
,
USSR Inventor s Certificate 1573817, 1990; SSSR
Byull. Izobr., 1990, no. 23.
. Fuson, R.G., Reaction of Organic Compounds: a
Textbook for the Advanced Student, New York: John
Wiley & Sons, 1962,
On completion the nitration the workup of the
reaction mixture and isolation of the target nitro-
sulfide V was performed similarly to the above
described procedure for nitrosulfide IV. The crude
5. Ingold, C.K., Structure and Mechanism in Organic
Chemistry, Cornell Univ Pr., 1969.
6. Mathier, G. and Pinakot, R., Kurs teoreticheskikh
osnov organicheskoi khimii (Treatise of Fundamentals
of Organic Chemistry), Moscow: Mir, 1975.
7. Kern, F. and Sandberg, R., Uglublennyi kurs orga-
nicheskoi khimii (Treatise of Organic Chemistry),
Moscow: Khimiya, 1981.
4-acetylamino-2 ,3-dinitrodiphenyl sulfide V was
obtained in 73% yield; content ot the main substance
was no less than 97%.
In nitration of 4-acetylamino-2 -nitrodiphenyl
ether (III) to a dispersion of 163.2 g (0.6 mol) of the
ether in 350 ml of acetic acid was added at 20 25 C
8
. Fieser, L.F. and Fieser, M., Reagents for Organic
Synthesis, New York: John Wiley.
9
. Passerini, R., Bull. Sci. Fac. Chim. Ind. Bologna,
7
6 ml (82 g, 0.8 mol) of acetic anhydride, and drop-
1
950, no. 8, p. 126.
wise was added 77 ml (115.5 g, 1.65 mol) of nitric
acid ( 1.5 g cm ). The reaction mixture was stirred
3
10. Orlova, E.Yu., Khimiya i tekhnologiya brizantnykh
vzryvchatykh veshchestv (Chemistry and Technology
of High Explosive), Moscow: Khimiya, 1981,
pp. 34 38.
1. Schoffeld, K., Aromatic Nitration, Cambridge: Cam-
bridge University Press, 1980, pp. 376 381.
2. Gorelik, M.V. and Efros, L.S., Osnovy khimii i tekh-
nologii aromaticheskikh soedinenii (Foundamentals of
Chemistry and Technology of Aromatic Compounds),
Moscow: Khimiya, 1992, pp. 149 150.
at room temperature for 20 25 min, and then it was
heated to 40 45 C, and stirring at this temperature
continued for 4 5 h. The reaction mixture was poured
into water, the precipitate was filtered off, washed
with water, and dried. We obtained 176 g (93%) of
crude 4-acetylamino-2 ,3-dinitrodiphenyl ether (VI)
with content of the main substance 98%, mp 98 99 C,
Rf of nitroether VI 0.56, of initial ether III 0.30
1
1
(
eluent benzene ethanol, 10: 2). Found, %: C 53.05;
H 3.52; N 13.28. C H N O . Calculated, %: C
13. Weigand, C. and Hilgetag, G., Organisch-Chemische
Experimentierkunst, Leipzig: Johann Ambrosis Barth.
1
4
11
3
6
5
3.00; H 3.49; N 13.24.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 6 2002