Synthesis of Amides by Nucleophilic Substitution of Hydrogen in 3-Nitropyridine

Article abstract of DOI:10.1134/S1070428018060076

3-Nitropyridine reacted with nitrogen-centered carboxylic acid amide anions in anhydrous DMSO in the presence of K₃Fe(CN)₆ via oxidative nucleophilic substitution of hydrogen to give previously unknown N-(5-nitropyridin-2-yl) carboxa

Full text of DOI:10.1134/S1070428018060076

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2018, Vol. 54, No. 6, pp. 867–872. © Pleiades Publishing, Ltd., 2018.
Original Russian Text © G.A. Amangasieva, I.V. Borovlev, O.P. Demidov, E.K. Avakyan, A.A. Borovleva, 2018, published in Zhurnal Organicheskoi Khimii,
2018, Vol. 54, No. 6, pp. 865–870.
Synthesis of Amides by Nucleophilic Substitution
of Hydrogen in 3-Nitropyridine
G. A. Amangasievaa, I. V. Borovleva,* O. P. Demidova, E. K. Avakyana, and A. A. Borovlevaa
a North Caucasus Federal University, ul. Pushkina 1a, Stavropol, 355009 Russia
*e-mail: ivborovlev@rambler.ru
Received September 13, 2017
Abstract—3-Nitropyridine reacted with nitrogen-centered carboxylic acid amide anions in anhydrous DMSO
in the presence of K3Fe(CN)6 via oxidative nucleophilic substitution of hydrogen to give previously unknown
N-(5-nitropyridin-2-yl) carboxamides. The reaction of nitrobenzene with urea anion in DMSO enabled one-pot
synthesis of bis(4-nitrophenyl)amine.
DOI: 10.1134/S1070428018060076
The problem of direct C–H functionalization of
aromatic compounds, e.g., by nucleophilic substitution
without preliminary introduction of a halogen atom or
other substituent into the aromatic ring, is important in
modern organic chemistry. Among other methods,
oxidative nucleophilic substitution of hydrogen [1–4],
which is widely applicable to π-deficient arenes and
hetarenes, provides a good alternative to cross-cou-
pling reactions catalyzed by transition metals [5].
The SNH methodology has already found application
in industry [6], and it largely conforms to the “green
chemistry” principles [7, 8].
AgPy2MnO4, AgMnO4) showed that the best results
were obtained with a complex oxidant, dipyridinesilver
permanganate (AgPy2MnO4) [13]. Verbeeck et al. [14]
measured the primary kinetic isotope effect in the
oxidative alkylamination of 3-nitropyridine and found
that the rate-determining stage is the oxidation of inter-
mediate σH-adduct. Therefore, the apparent reaction
rate depends on both equilibrium concentration of the
σH-adduct and on the oxidant nature.
The oxidative SNH-arylamination of 3-nitropyridines
with preliminarily generated 2-, 3-, and 4-aminopyri-
dine anions was studied in detail in [5]. The authors
used nitrobenzene as a mild oxidant for the oxidation
of σH-adducts formed in the first stage. In all cases, the
N-nucleophile was directed to the para position with
respect to the nitro group to afford products of oxida-
tive nucleophilic substitution of hydrogen even in the
presence of readily departing groups [5].
Due to cooperative effect of electron-withdrawing
nitro group and endocyclic nitrogen atom, 3-nitropyri-
dine is a highly electrophilic heteroaromatic compound
which readily reacts with various nucleophiles. For
example, oxidative amination of 3-nitropyridine in the
system liquid ammonia–KMnO4 is not selective, and it
involves all ortho and para positions with respect to
the nitro group, giving rise to a mixture of three iso-
meric 3-nitropyridinamines [9]. The oxidative amina-
tion of 3-nitropyridine was later carried out with the
use of ammonia in aqueous potassium permanganate,
as well as in the system DMSO–KMnO4 [10, 11].
Oxidative SHN-alkylamination of 3-nitropyridines
has been well documented [12–14]. These reactions
are usually accomplished with excess alkyl- or dialkyl-
amine used as solvent in the presence of an oxidant.
Comparison of the efficiency of most common
oxidants used for this purpose (KMnO4, CAN,
Vicarious nucleophilic amination of 3-nitropyri-
dines with such reagents as hydroxylamine [15],
1,2,4-triazol-4-amine [15], O-methylhydroxylamine
[16], and sulfenamides [17] was also thoroughly
studied. If one more electron-withdrawing substituent
was present in the pyridine ring, the nitro group itself
was replaced by nucleophile. For instance, the nitro
group in methyl 3-nitropyridine-4-carboxylate was re-
placed by the action of some anionic nucleophiles [18].
Unlike amination of azines, examples of SNH-amida-
tion reactions remain very rare. The possibility of such
reaction with nitrobenzene was reported for the first
867

AMANGASIEVA et al.
868
Scheme 1.
O
O
NaH, DMSO
–H2
R
NH2
R
NH– Na+
(1) RC(O)NH–, DMSO
K3[Fe(CN)6], 20°C
(2) H2O
NO2
NO2
NO2
O
[O]
O
H
...
–H2O
N
N
R
N
N
N
H
R
H
1
2a–2h
3a–3h
R = Ph (a), 4-MeC6H4 (b), 4-MeOC6H4 (c), 4-O2NC6H4 (d), 2-O2NC6H4 (e), Me (f), Et (g), i-Pr (h).
time in the early 1990s [19]. Later on, benzamidation
of 1,3-dinitrobenzene under anaerobic conditions
afforded N-(2,4-dinitrophenyl)benzamide in 12%
yield [20].
It was not surprising that an attempt to introduce
a formamide group into the 3-nitropyridine molecule
under analogous conditions was unsuccessful. In this
case, the only isolated compound was known 5-nitro-
pyridin-2-amine (4). The yield of 4 was as low as 16%,
whereas the conversion of 3-nitropyridine was com-
plete (according to the TLC data). Presumably, primary
amine 4 is oxidized with K3Fe(CN)6 to give water-
soluble by-products. Previously reported reaction of
3-nitropyridine derivative with formanilide anion was
also accompanied by hydrolysis [29].
In continuation of our studies on direct introduction
of a carboxamido group into 1,3,7-triazapyrene
[21, 22] and acridine molecules [23, 24], we set our-
selves the task of elucidating whether analogous
SNH-functionalization of 3-nitropyridine is possible.
The conditions for the introduction of an amido
group into 3-nitropyridine molecule were optimized
using benzamide as model nucleophile. The corre-
sponding anion was generated by the action of sodium
hydride in anhydrous DMSO. If atmospheric oxygen
was used as oxidant, the reaction at room temperature
was too slow, and the complete conversion was not
achieved after 48 h. Raising the temperature to 65–
70°C accelerated the process, but elevated temperature
also favored formation of a number of by-products.
As in other SNH reactions [23–28], better results were
obtained in the presence of K3Fe(CN)6 as one-electron
oxidant. The reaction of 3-nitropyridine with benz-
amide in the presence of K3Fe(CN)6 was complete in
1 h at room temperature, and N-(5-nitropyridin-2-
yl)benzamide (3a) was obtained in 79% yield
(Scheme 1). Other aromatic carboxamides containing
both electron-donating and electron-withdrawing sub-
stituents in the benzene ring reacted in a similar way
under analogous conditions to give previously un-
known amides 3b–3e in 70–88% yield.
We then proceeded with studying the behavior of
3-nitropyridine toward urea anion in DMSO. The urea
anion is a good nucleophile for the introduction of
an amino group into the 1,3,7-triazapyrene and acri-
dine molecules via SNH [21–24] or SNAr reaction
[30, 31]. Atmospheric oxygen acts as oxidant in the
SNH reactions with urea anion. For example, acridin-2-
amine was thus synthesized from acridine in 78% yield
[24] which significantly exceeded the yield in the
Chichibabin synthesis [32, 33].
However, the use of urea anion for SNH-amination of
3-nitropyridine proved less successful than in the
reactions with 1,3,7-triazapyrene and acridine. The
reaction of 1 with 2 equiv of urea anion in anhydrous
DMSO without protection from atmospheric oxygen
was accompanied by considerable tar formation, and
we succeeded in isolating from the reaction mixture
two products with low yields, expected 5-nitropyridin-
2-amine (4) and 5-nitropyridin-2(1H)-one (5)
(Scheme 2).
As in the reactions with 1,3,7-triazapyrenes [21],
the yields of compounds 3f–3h from aliphatic acid
amides (acetamide, propionamide, and isobutyramide)
were considerably lower (27–48%), which may be due
to their low hydrolytic stability. We believe that they
are hydrolyzed not only during the isolation stage but
also in the reaction mixture which contains water
liberated as a result of oxidative aromatization of
σH-adducts 2 (Scheme 1).
Our attempts to improve the yield of 4 by varying
the temperature, using K3Fe(CN)6 and other solvents
(both polar and nonpolar), and varying the reactant
ratio were unsuccessful. In all cases, by-product 5
was formed. Probably, urea anion acts as both N-
and O-nucleophile [22] in the reaction with 3-nitro-
pyridine.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 54 No. 6 2018

SYNTHESIS OF AMIDES BY NUCLEOPHILIC SUBSTITUTION OF HYDROGEN
869
Scheme 2.
NO2 (1) H2NC(O)NH–, DMSO, 20°C
(2) H2O
NO2
NO2
+
N
H2N
N
O
N
H
1
4
5
Scheme 3.
(1) H2NC(O)NH–
DMSO, O2, 20°C
(2) H2O
NO2
NO2
O2N
NO2
O
+
H2N
N
H
N
H
6
7
We also tried to use nitrobenzene as a mild oxidant
for the aromatization of σH-adduct; however, as
a result, even more complex mixture of products was
obtained. We presumed that under the given conditions
nitrobenzene itself is also capable of reacting with urea
anion. In fact, the reaction of nitrobenzene with pre-
liminarily prepared urea anion in DMSO was complete
at room temperature with the formation of a mixture of
two products, 4-nitrophenylurea (6) and bis(4-nitro-
phenyl)amine (7) (Scheme 3).
showed that, in fact, nitrobenzene reacts with 4-nitro-
aniline anion under the same conditions to afford 61%
of bis(4-nitrophenyl)amine (7) (see Experimental).
In summary, we have developed a procedure for the
synthesis of N-(5-nitropyridin-2-yl) carboxamides by
direct nucleophilic substitution of hydrogen in 3-nitro-
pyridine using N-centered carboxamide anions as nu-
cleophiles. Nitrobenzene reacts with urea in DMSO in
the presence of sodium hydride at room temperature
to give bis(4-nitrophenyl)amine as a result of tandem
SNH–SNH reaction.
Undoubtedly, this reaction involves the addition of
urea anion to give the corresponding σH-adduct and
oxidative aromatization of the latter by the action of
atmospheric oxygen. However, SNH-carbamoylamina-
tion products analogous to 6 were not isolated in the
reactions with 1,3,7-triazapyrene [21, 22] and acridine
[23, 24], since these compounds were converted to
primary amines under the given conditions. More
stable 4-nitrophenylurea is also partially involved in
further transformations with successive generation of
anions A and B and elimination of isocyanic acid
(Scheme 4), but intermediate 4-nitroaniline anion C
thus formed reacts with nitrobenzene, yielding SNH-aryl-
amination product 7. Bis(4-nitrophenyl)amine (7) was
formed as the only product (yield 57%) when the reac-
tion was carried out at 70°C. By special experiment we
EXPERIMENTAL
1
The H and 13C NMR spectra were recorded on
a Bruker Avance HD 400 spectrometer at 400 and
100 MHz, respectively; the chemical shifts were
measured relative to the residual proton and carbon
signals of deuterated dimethyl sulfoxide [34]
(DMSO-d5, δ 2.50 ppm; DMSO-d6, δC 40.45 ppm) or
tetramethylsilane (in CDCl3). The mass spectra were
obtained with a Bruker UHR-TOF Maxis™ Impact
mass spectrometer (electrospray ionization). The IR
spectra were measured on a Shimadzu IRTracer-100
instrument. The melting points were determined with
REACH Devices RD-MP and Electrotermal IA 9200
Scheme 4.
NO2
NO2
NO2
~H+
O
O
O–
6
–H+
H2N
N
–HN
N
HN
N
H
H
A
B
NO2
PhNO2, O2, H2O
7
–HNCO
HN
C
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 54 No. 6 2018

AMANGASIEVA et al.
870
melting point apparatuses. Compounds obtained by
different methods were identified by comparing their
IR spectra. The progress of reactions and the purity of
the isolated compounds were monitored by TLC on
Silufol UV-254 plates. Sodium hydride was used as
a 60% suspension in mineral oil (Merck). Commercial
reagents were used without additional purification.
M + H 258.0873. Found: m/z 280.0700 [M + Na]+.
C13H11N3NaO3. Calculated: M + Na 280.0693.
4-Methoxy-N-(5-nitropyridin-2-yl)benzamide
(3c). Reaction time 1.5 h. Yield 102 mg (75%), yellow
crystals, mp 195–196°C (from EtOH). IR spectrum
(film), ν, cm–1: 3100, 1679, 1601, 1578, 1496, 1342.
1H NMR spectrum (CDCl3), δ, ppm: 3.83 s (3H,
OCH3), 6.95 d (2H, 3-H, 5-H, J = 8.8 Hz), 7.85 d (2H,
2-H, 6-H, J = 8.8 Hz), 8.47 d.d (1H, 4′-H, J = 9.2,
2.5 Hz), 8.51 d (1H, 3′-H, J = 9.2 Hz), 8.77 br.s (1H,
NH), 9.09 d (1H, 6′-H, J = 2.7 Hz). 13C NMR spectrum
(CDCl3), δC, ppm: 54.6, 111.9, 113.3, 124.2, 128.4,
133.1, 139.5, 143.8, 154.7, 162.5, 164.1. Found:
m/z 296.0648 [M + Na]+. C13H11N3NaO4. Calculated:
M + Na 296.0642.
Compounds 3a–3h (general procedure). Sodium
hydride, 40 mg (1 mmol), was added with stirring to
a solution of 1 mmol of the corresponding amide in
4 mL of anhydrous DMSO. When the evolution of
hydrogen ceased (~0.5 h), 62 mg (0.5 mmol) of
3-nitropyridine and 329 mg (1 mmol) of K3Fe(CN)6
were added, and the mixture was vigorously stirred for
1–3 h at room temperature. The mixture was then
poured into 50 mL of cold water and neutralized with
dilute aqueous HCl to pH ~7. The precipitate was
filtered off, washed with water, and dried. The prod-
ucts were additionally purified by recrystallization
from appropriate solvents.
4-Nitro-N-(5-nitropyridin-2-yl)benzamide (3d).
Reaction time 1 h. Yield 127 mg (88%), yellow–
orange crystals, mp 219–220°C (from EtOH). IR spec-
trum (film), ν, cm–1: 3465, 3181, 1676, 1582, 1562,
1
1345. H NMR spectrum (DMSO-d6), δ, ppm: 8.24 d
N-(5-Nitropyridin-2-yl)benzamide (3a). Reaction
time 1 h. Yield 96 mg (79%), gold yellow crystals,
mp 168–169°C (from EtOH). IR spectrum (film), ν,
(2H, 2-H, 6-H, J = 8.8 Hz), 8.35 d (2H, 3-H, 5-H, J =
8.8 Hz), 8.44 d (1H, 3′-H, J = 9.2 Hz), 8.69 d.d (1H,
4′-H, J = 9.2, 2.8 Hz), 9.25 d (1H, 6′-H, J = 2.8 Hz),
11.90 s (1H, NH). 13C NMR spectrum (DMSO-d6), δC,
ppm: 113.8, 123.5, 129.9, 134.3, 139.1, 140.4, 144.6,
149.6, 156.1, 165.4. Found: m/z 289.0580 [M + H]+.
C12H9N4O5. Calculated: M + H 289.0567.
1
cm–1: 3265, 1686, 1582, 1535, 1505, 1342. H NMR
spectrum, δ, ppm: in DMSO-d6: 7.55 m (2H, 3-H,
5-H), 7.64 t (1H, 4-H, J = 7.4 Hz), 8.03 d (2H, 2-H,
6-H, J = 7.1 Hz), 8.44 d (1H, 3′-H, J = 9.3 Hz),
8.66 d.d (1H, 4′-H, J = 9.3, 2.8 Hz), 9.23 d (1H, 6′-H,
J = 2.8 Hz), 11.54 br.s (1H, NH); in CDCl3: 7.48 d.d
(2H, 3-H, 5-H, J = 7.3, 7.4 Hz), 7.57 d.t (1H, 4-H, J =
7.4, 1.1 Hz), 7.87 d.d (2H, 2-H, 6-H, J = 7.1, 1.1 Hz),
8.47 d.d (1H, 4′-H, J = 9.2, 2.5 Hz), 8.53 d (1H, 3′-H,
J = 9.2 Hz), 8.87 br.s (1H, NH), 9.09 d (1H, 6′-H, J =
2.5 Hz). 13C NMR spectrum (DMSO-d6), δC, ppm:
113.6, 128.4, 128.5, 132.6, 133.4, 134.2, 140.1, 144.6,
156.5, 166.7. Found: m/z 244.0697 [M + H]+.
C12H10N3O3. Calculated: M + H 244.0717. Found:
m/z 266.0546 [M + Na]+. C12H9N3NaO3. Calculated:
M + Na 266.0536.
2-Nitro-N-(5-nitropyridin-2-yl)benzamide (3e).
Reaction time 3 h. Yield 104 mg (72%), yellow crys-
tals, mp 216–217°C (from EtOH). IR spectrum (film),
ν, cm–1: 3276, 1673, 1581, 1505, 1345. 1H NMR spec-
trum (DMSO-d6), δ, ppm: 7.79–7.91 m (3H, 4-H, 5-H,
6-H), 8.20 d (1H, 3-H, J = 8.2 Hz), 8.39 d (1H, 3′-H,
J = 9.2 Hz), 8.69 d.d (1H, 4′-H, J = 9.2, 2.8 Hz), 9.20 d
(1H, 6′-H, J = 2.8 Hz), 11.95 s (1H, NH). 13C NMR
spectrum (DMSO-d6), δC, ppm: 113.2, 124.3, 129.4,
131.4, 131.8, 134.47, 134.52, 140.3, 144.8, 145.9,
155.8, 166.0. Found: m/z 289.0567 [M + H]+.
C12H9N4O5. Calculated: M + H 289.0567. Found:
m/z 311.0396 [M + Na]+. C12H8N4NaO5. Calculated:
M + Na 311.0387.
4-Methyl-N-(5-nitropyridin-2-yl)benzamide (3b).
Reaction time 1.5 h. Yield 90 mg (70%), yellow
crystals, mp 196–197°C (from EtOH). IR spectrum
(film), ν, cm–1: 3269, 1687, 1583, 1532, 1501, 1339.
1H NMR spectrum (CDCl3), δ, ppm: 2.38 s (3H, CH3),
7.26 d (2H, 3-H, 5-H, J = 8.1 Hz), 7.76 d (2H, 2-H,
6-H, J = 8.1 Hz), 8.46 d.d (1H, 4′-H, J = 9.2, 2.7 Hz),
8.51 d (1H, 3′-H, J = 9.2 Hz), 8.90 br.s (1H, NH),
9.03 d (1H, 6′-H, J = 2.7 Hz). 13C NMR spectrum
(CDCl3), δC, ppm: 20.6, 112.0, 126.4, 128.8, 129.3,
133.1, 139.5, 143.0, 143.8, 154.6, 164.7. Found:
m/z 258.0875 [M + H]+. C13H12N3O3. Calculated:
N-(5-Nitropyridin-2-yl)acetamide (3f). Reaction
time 2 h. Yield 31 mg (34%), light yellow crystals,
mp 198–199°C (from PhH). IR spectrum (film), ν,
1
cm–1: 3205, 1687, 1544, 1496, 1344. H NMR spec-
trum (DMSO-d6), δ, ppm: 2.16 s (3H, CH3), 8.28 d
(1H, 3′-H, J = 9.3 Hz), 8.58 d.d (1H, 4′-H, J = 9.3,
2.8 Hz), 9.16 d (1H, 6′-H, J = 2.8 Hz), 11.22 br.s (1H,
NH). 13C NMR spectrum (DMSO-d6), δC, ppm: 24.1,
112.4, 134.2, 139.7, 144.7, 156.2, 170.2. Found:
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SYNTHESIS OF AMIDES BY NUCLEOPHILIC SUBSTITUTION OF HYDROGEN
871
m/z 204.0380 [M + Na]+. C7H7N3NaO3. Calculated:
M + Na 204.0380.
(7:3) and then with ethyl acetate (both fractions were
yellow). Removal of the solvent from the first fraction
left 7.6 mg (11%) of 5-nitropyridin-2-amine (4), and
6.3 mg (9%) of 5-nitropyridin-2(1H)-one (5) was
isolated from the second fraction.
N-(5-Nitropyridin-2-yl)propanamide (3g). Reac-
tion time 2 h. Yield 26 mg (27%), brown crystals,
mp 152–153°C (from PhH). IR spectrum (film), ν,
1
cm–1: 3203, 1682, 1533, 1501, 1341. H NMR spec-
5-Nitropyridin-2(1H)-one (5). Yellow crystals,
mp 187–188°C; published data [35]: mp 182–183°C.
1H NMR spectrum (DMSO-d6), δ, ppm: 6.42 d (1H,
3-H, J = 10.1 Hz), 8.11 d.d (1H, 4-H, J = 10.1, 3.2 Hz),
8.65 d (1H, 6-H, J = 3.2 Hz), 12.65 br.s (1H, NH).
13C NMR spectrum (DMSO-d6), δC, ppm: 98.8, 119.01,
134.3, 138.7, 162.07. Found: m/z 141.0294 [M + H]+.
C5H5N2O3. Calculated: M + H 141.0292.
trum (DMSO-d6), δ, ppm: 1.07 t (3H, CH3, J =
7.5 Hz), 2.46 q (2H, CH2, J = 7.5 Hz), 8.30 d (1H,
3′-H, J = 9.3 Hz), 8.59 d.d (1H, 4′-H, J = 9.3, 2.8 Hz),
9.15 d (1H, 6′-H, J = 2.8 Hz), 11.18 br.s (1H, NH).
13C NMR spectrum (DMSO-d6), δC, ppm: 9.1, 29.5,
112.3, 134.2, 139.6, 144.8, 156.2, 173.8. Found:
m/z 218.0380 [M + Na]+. C8H9N3NaO3. Calculated:
M + Na 218.0380.
Reaction of nitrobenzene with urea anion.
a. A 60% suspension of sodium hydride, 80 mg
(2 mmol), was added with stirring to a solution of
60 mg (1 mmol) of urea in 4 mL of anhydrous DMSO.
When the evolution of hydrogen ceased (~0.5 h),
61.5 mg (0.5 mmol) of nitrobenzene was added, and
the mixture was vigorously stirred for 25 h at room
temperature. The mixture was then poured into 50 mL
of cold water, and the precipitate of compound 7 was
filtered off, washed with water, and dried. The filtrate
was extracted with ethyl acetate (3×10 mL), and the
combined extracts were evaporated to obtain com-
pound 6. The products were purified by recrystal-
lization from appropriate solvents.
2-Methyl-N-(5-nitropyridin-2-yl)propanamide
(3h). Reaction time 3 h. Yield 50 mg (48%), light
yellow crystals, mp 175–176°C (from PhH). IR spec-
trum (film), ν, cm–1: 3490, 3357, 1691, 1590, 1501,
1
1332. H NMR spectrum (DMSO-d6), δ, ppm: 1.10 d
[6H, CH(CH3)2, J = 6.8 Hz], 2.81 m (1H, CH), 8.30 d
(1H, 3′-H, J = 9.3 Hz), 8.58 d.d (1H, 4′-H, J = 9.3,
2.7 Hz), 9.15 d (1H, 6′-H, J = 2.7 Hz), 11.18 br.s (1H,
NH). 13C NMR spectrum (DMSO-d6), δC, ppm: 19.2,
34.7, 112.5, 134.2, 139.7, 144.7, 156.4, 177.1. Found:
m/z 210.0872 [M + H]+. C9H12N3O3. Calculated:
M + H 210.0873.
5-Nitropyridin-2-amine (4). Reaction time 1.5 h.
Yield 15 mg (16%), yellow crystals, mp 185–186°C
(from PhH); published data [9]: mp 188–189°C. IR
spectrum (film), ν, cm–1: 3394, 3319, 1652, 1601,
N-(4-Nitrophenyl)urea (6). Yield 23 mg (25%),
light brown crystals, mp 269–270°C (from EtOAc–
1
PhH). H NMR spectrum (DMSO-d6), δ, ppm:
1
1572, 1332, 1318. H NMR spectrum (DMSO-d6), δ,
6.21 br.s (2H, NH2), 7.63 d (2H, 2-H, 6-H, J = 9.2 Hz),
8.13 d (2H, 3-H, 5-H, J = 9.2 Hz), 9.31 br.s (1H, NH).
13C NMR spectrum (DMSO-d6), δC, ppm: 116.9, 125.1,
140.4, 147.3, 155.3. Found: m/z 182.0566 [M + H]+.
C7H8N3O3. Calculated: M + H 182.0560.
ppm: 6.49 d (1H, 3-H, J = 9.3 Hz), 7.54 br.s (2H,
NH2), 8.12 d.d (1H, 4-H, J = 9.3, 2.8 Hz), 8.84 d (1H,
6-H, J = 2.8 Hz). 13C NMR spectrum (DMSO-d6), δC,
ppm: 107.2, 132.6, 134.4, 147.0, 163.3. Found:
m/z 140.0460 [M + H]+. C5H6N3O2. Calculated: M + H
140.0455.
Reaction of 3-nitropyridine with urea anion.
Sodium hydride, 40 mg (1 mmol), was added at room
temperature to a solution of 60 mg (1 mmol) of urea in
1.25 mL of anhydrous DMSO. When the evolution
of hydrogen ceased (~0.5 h), 62 mg (0.5 mmol) of
3-nitropyridine was added, and the mixture was vigor-
ously stirred for 2 h at room temperature. The mixture
was then poured into 50 mL of cold water, neutralized
with dilute aqueous HCl to pH ~7, and filtered. The
aqueous filtrate was extracted with ethyl acetate (5×10
mL), the combined extracts were evaporated to dryness
under reduced pressure, and the residue was purified
by dry-column flash chromatography on silica gel. The
column was eluted first with benzene–ethyl acetate
4-Nitro-N-(4-nitrophenyl)aniline (7). Yield 49 mg
(38%), orange crystals, mp 219–220°C (from PhH).
1H NMR spectrum (DMSO-d6), δ, ppm: 7.36 d (4H,
o-H, J = 9.2 Hz), 8.20 d (4H, m-H, J = 9.2 Hz),
9.98 br.s (1H, NH). 13C NMR spectrum (DMSO-d6),
δC, ppm: 117.1, 125.8, 140.5, 147.6. Found:
m/z 282.0490 [M + Na]+. C12H9N3NaO4. Calculated:
M + Na 282.0485.
b. A 60% suspension of sodium hydride, 80 mg
(2 mmol), was added with stirring to a solution of
60 mg (1 mmol) of urea in 4 mL of anhydrous DMSO.
When the evolution of hydrogen ceased (~0.5 h),
61.5 mg (0.5 mmol) of nitrobenzene was added, and
the mixture was vigorously stirred for 3 h at 70°C. The
mixture was then poured into 50 mL of cold water, and
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 54 No. 6 2018

AMANGASIEVA et al.
872
15. Bakke, J.M., Svensen, H., and Trevisan, R., J. Chem.
Soc., Perkin Trans. 1, 2001, p. 376.
16. Seko, S. and Miyake, K., Chem. Commun., 1998,
the precipitate of compound 7 was filtered off, washed
with water, dried, and recrystallized from an appro-
priate solvent. Yield 74 mg (57%).
no. 15, p. 1519.
c. A 60% suspension of sodium hydride, 20 mg
(0.5 mmol), was added with stirring to a solution of
0.5 mmol of 4-nitroaniline in 4 mL of anhydrous
DMSO. When the evolution of hydrogen ceased
(~0.5 h), 61.5 mg (0.5 mmol) of nitrobenzene was
added, and the mixture was vigorously stirred for 25 h
at room temperature. The mixture was then poured into
50 mL of cold water, and the precipitate of compound
7 was filtered off, washed with water, dried, and
recrystallized from benzene. Yield 79 mg (61%).
17. Makosza, M. and Bialecki, M., J. Org. Chem., 1998,
vol. 63, p. 4878.
18. Holt, J., Tjosås, F., Bakke, J.M., and Fiksdahl, A.,
J. Heterocycl. Chem., 2004, vol. 41, p. 987.
19. Stern, M.K. and Cheng, B.K., J. Org. Chem., 1993,
vol. 58, p. 6883.
20. Gulevskaya, A.V., Tyaglivaya, I.N., Verbeeck, S.,
Maes, U.W., and Tkachuk, A.V., Arkivoc, 2011,
part (ix), p. 238.
21. Borovlev, I.V., Demidov, O.P., Kurnosova, N.A., Aman-
gasieva, G.A., and Avakyan, E.K., Chem. Heterocycl.
Compd., 2015, vol. 51, p. 170.
22. Borovlev, I.V., Demidov, O.P., Amangasieva, G.A.,
Avakyan, E.K., and Kurnosova, N.A., Arkivoc, 2016,
part (iii), p. 58.
This study was performed under financial support
by the Ministry of Education and Science of the
Russian Federation in the framework of state assign-
ment (project nos. 4.141.2014/K, 4.6306.2017/BCh).
REFERENCES
23. Demidov, O.P., Borovlev, I.V., Amangasieva, G.A., and
Avakyan, E.K., Chem. Heterocycl. Compd., 2016,
vol. 52, p. 104.
24. Borovlev, I.V., Demidov, O.P., Amangasieva, G.A., and
Avakyan, E.K., Tetrahedron Lett., 2016, vol. 57,
p. 3608.
1. Chupakhin, O.N. and Charushin, V.N., Tetrahedron
Lett., 2016, vol. 57, p. 2665.
2. Charushin, V.N. and Chupakhin, O.N., Top. Heterocycl.
Chem., 2014, vol. 37, p. 1.
3. Gulevskaya, A.V. and Pozharskii, A.F., Top. Heterocycl.
Chem., 2014, vol. 37, p. 179.
4. Makosza, M. and Wojciechowski, K., Top. Heterocycl.
Chem., 2014, vol. 37, p. 51.
25. Demidov, O.P., Borovlev, I.V., Saigakova, N.A., Nemy-
kina, O.A., Demidova, N.V., and Pisarenko, S.V., Chem.
Heterocycl. Compd., 2011, vol. 47, p. 114.
26. Demidov, O.P., Borovlev, I.V., Pisarenko, S.V., Nemy-
kina, O.A., and Saigakova, N.A., Chem. Heterocycl.
Compd., 2010, vol. 46, p. 636.
5. Patriciu, O.-I., Finaru, A.-L., Sandulescu, I., and
Guillaumet, G., Synthesis, 2007, p. 3868.
27. Borovlev, I.V., Demidov, O.P., and Saigakova, N.A.,
6. Bashkin, J.K., Rains, R., and Stern, M., Green Chem.,
Russ. Chem. Bull., Int. Ed., 2011, vol. 60, p. 1784.
1999, vol. 1, p. G41.
28. Borovlev, I.V., Demidov, O.P., Saigakova, N.A., Pisa-
renko, S.V., and Nemykina, O.A., J. Heterocycl. Chem.,
2011, vol. 48, p. 1206.
7. Constable, D.J.C., Dunn, P.J., Hayler, J.D., Hum-
phrey, G.R., Leazer, J.L., Linderman, R.J., Lorenz, K.,
Manley, J., Pearlman, B.A., Wells, A., Zaks, A., and
Zhang, T.Y., Green Chem., 2007, vol. 9, p. 411.
29. Finch, N., Campbell, T.R., Gemenden, C.W., and
8. Utepova, I.A., Trestsova, M.A., Chupakhin, O.N.,
Charushin, V.N., and Rempel, A.A., Green Chem., 2015,
vol. 17, p. 4401.
9. Wozniak, M., Baranski, A., and Szpakiewicz, B., Justus
Liebigs Ann. Chem., 1991, p. 875.
Povalski, H.J., J. Med. Chem., 1980, vol. 23, p. 1405.
30. Amangasieva, G.A., Borovlev, I.V., Demidov, O.P.,
Kurnosova, N.A., and Avakyan, E.K., Chem. Hetero-
cycl. Compd., 2015, vol. 51, p. 586.
31. Borovlev, I.V., Demidov, O.P., Amangasieva, G.A.,
Avakyan, E.K., and Kurnosova, N.A., J. Heterocycl.
Chem., 2017, vol. 54, p. 406.
10. Bakke, J.M. and Svensen, H., Tetrahedron Lett., 2001,
vol. 42, p. 4393.
32. Pozharskii, A.F. and Konstantinchenko, A.A., Chem.
Heterocycl. Compd., 1972, vol. 8, p. 1518.
11. Bakke, J.M., J. Heterocycl. Chem., 2005, vol. 42, p. 463.
12. Szpakiewicz, B. and Wozniak, M., J. Prakt. Chem.,
33. Kitahara, T., Ishihara, Y., and Takano, J., Nippon
Kagaku Zasshi, 1997, vol. 12, p. 876; Chem. Abstr.,
1997, vol. 128, no. 22802.
34. Gottlieb, H.E., Kotlyar, V., and Nudelman, A., J. Org.
Chem., 1997, vol. 62, p. 7512.
1999, vol. 341, p. 75.
13. Gulevskaya, A.V., Maes, B.U.W., Meyers, C.,
Herrebout, W., and van der Veken, B.J., Eur. J. Org.
Chem., 2006, no. 23, p. 5305.
14. Verbeeck, S., Herrebout, W.A., Gulevskaya, A.V., van
der Veken, B.J., and Maes, B.U.W., J. Org. Chem.,
2010, vol. 75, p. 5126.
35. Kokars, V., Yanishevskii, A., and Kampars, V., Chem.
Heterocycl. Compd., 2002, vol. 38, p. 805.
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