Reactions of 1-amino-2-nitroguanidine with 2-aryl(hetaryl)-1-nitro-1-ethoxycarbonyl(benzoyl)ethenes

Article abstract of DOI:10.1134/S1070363214080088

Reactions of 1-amino-2-nitroguanidine with 2-aryl(hetaryl)-1-nitro-1-ethoxycarbonyl(benzoyl)-ethenes proceed via initial formation the aza-Michael product, are accompanied by liberation of nitroacetic ester (or nitroacetophenone), and result in N-aryl(het

Full text of DOI:10.1134/S1070363214080088

ISSN 1070-3632, Russian Journal of General Chemistry, 2014, Vol. 84, No. 8, pp. 1496–1499. © Pleiades Publishing, Ltd., 2014.
Original Russian Text © T.P. Efimova, O.Yu. Ozerova, T.A. Novikova, R.I. Baichurin, V.M. Berestovitskaya, 2014, published in Zhurnal Obshchei Khimii,
2014, Vol. 84, No. 8, pp. 1268–1272.
Reactions of 1-Amino-2-nitroguanidine
with 2-Aryl(hetaryl)-1-nitro-1-ethoxycarbonyl(benzoyl)ethenes
T. P. Efimova, O. Yu. Ozerova, T. A. Novikova, R. I. Baichurin, and V. M. Berestovitskaya
Herzen State Pedagogical University of Russia, nab. reki Moiki 48, St. Petersburg, 191186 Russia
e-mail: kohrgpu@yandex.ru
Received March 17, 2014
Abstract—Reactions of 1-amino-2-nitroguanidine with 2-aryl(hetaryl)-1-nitro-1-ethoxycarbonyl(benzoyl)-
ethenes proceed via initial formation the aza-Michael product, are accompanied by liberation of nitroacetic
ester (or nitroacetophenone), and result in N-aryl(hetaryl)methylidene-N-(2-nitroguanidino)amines.
Keywords: nitroguanidine, gem-alkoxycarbonyl(benzoyl)nitroethene, N-aryl(hetaryl)methylidene-N-(2-nitro-
guanidino)amine
DOI: 10.1134/S1070363214080088
1-Amino-2-nitroguanidine is of particular interest
as a synthon for synthesis of valuable biologically
active and energy-rich compounds. In particular, some
guanidine-containing compounds are used as drugs
possessing hypotensive (clonidine, guanfacine, apra-
clonidine, and guanabenz) and hypoglycemic (phen-
formin, metformin, and buformin) activities [1–3].
Certain nitroguanidine derivatives have found
agriculture application. For instance, patent [4] describes
method for N-arylmethylidene-N-(2-nitroguanidino)-
amines preparation and the products use as insecticides.
nitroguanidine, yielding the amination products: 1-
nitro- and 2-aryl-1-bromo-1-nitro-2-(2-nitroguanidino-
amino)ethanes [5]. In the presence of basic catalyst or
upon prolonged refluxing the adducts derived from
gem-bromonitrostyrenes were cleaved to form N-
arylmethylidene-N-(2-nitroguanidino)amines.
Extending our studies in that area, herein we report
the reactions of 1-amino-2-nitroguanidine I with gem-
ethoxycarbonyl- and gem-benzoylnitroethenes. 1-
Amino-2-nitroguanidine I reacted with 2-aryl(hetaryl)-
1-nitro-1-ethoxycarbonylethenes II–V in aqueous-
alcoholic medium at 35–40°C within 40 min to yield
high-melting crystalline N-aryl(hetaryl)methylidene-N-
Previously, we studied the reaction of 2-aryl-1-
nitro- and 1-bromo-1-nitroethenes with 1-amino-2-
Scheme 1.
R
X
R
H
NH
H2N
35−40oC, 40 min
NO2
NH
H2N
NH2
+
NH
EtOH/H2O (2 : 1)
NNO2
NNO2
NO2
X
I
II−V, VII−IX
− XCH2NO2
O
H
R
80oC, 5 min
NH
H2N
N
R
EtOH/H2O (3 : 1)
NNO2
X−XIII
X = COOC2H5, R = C6H5 (II), 4-CH3OC6H4 (III), 2-thienyl (IV), 2-furyl (V); X = COC6H5, R = C6H5 (VII), 2-thienyl
(VIII), 2-furyl (IX); R = C6H5 (X), 4-CH3OC6H4 (XI), 2-thienyl (XII), 2-furyl (XIII).
1496

REACTIONS OF 1-AMINO-2-NITROGUANIDINE
1497
Scheme 2.
C6H4NO2-4
H
4-O2NH4C6
I +
NO2
35−40oC, 40 min
HB
NHX
NH
H2N
NH
H2N
+
NO2
HA
COOEt
EtOH/H2O (2 : 1)
N
C6H4NO2-4
H
COOEt
NNO2
NNO2
XV
VI
XIV
78oC, EtOH
− O2NCH2COOEt
(2-nitroguanidino)amines X–XIII with yields of up to
Signals of the protons of all the structural fragments
90% (Scheme 1).
were identified in 1H NMR spectra of compounds XI–
XIII. Protons of the =CH, NH2, and NH groups
resonated in the weak field at 8.05–8.30, 8.11–8.76,
8.11–8.76, and 11.69–11.81 ppm, respectively. The
signals at 6.62–7.83 ppm were assigned to protons of
the aromatic and heterocyclic rings. IR spectra of
compounds XI–XIII contained sets of strong
absorption bands. Absorption bands of the N–H bonds
stretching were observed in the high-frequency part of
the spectra (3206–3222, 3343–3363, and 3438–
3477 cm–1). Absorption bands at 1612–1633 cm–1 could
be probably attributed to stretching of the C=N bond
and to deformation of the N–H bond. Absorbance at
1426–1440 and 1313–1338 cm–1 was assigned to the
NNO2 group stretching. IR spectral features of com-
pounds XI–XIII were in line with those of the struc-
turally similar compounds prepared previously [5, 6].
Apparently, the reactions proceeded via the initial
formation of the adducts followed by elimination of
nitroacetic ester. The elimination readiness depended
significantly on the nature of the substituent in the
aromatic ring: the electron-donating substituents were
expected to promote that process, and the electron-
withdrawing groups should have inhibited it. Indeed,
1-nitro-2-(4-nitrophenyl)-1-ethoxycarbonylethene VI
(containing the electron-withdrawing nitro group in
para-position of the aromatic ring) yielded a mixture
of the adduct XIV and the elimination product XV in
the 1 : 1 ratio (1H NMR) in the reaction with the
similar conditions (1H NMR). Attempts to separate that
mixture were not successful: recrystallization from
ethanol resulted in azomethine XV (Scheme 2).
Reactions of 1-amino-2-nitroguanidine with gem-
benzoylnitroethenes VII–IX as well as with their ester
analogs proceeded via the AdN–E mechanism, i.e., they
were accompanied by nitroacetophenone elimination
and yielded the corresponding N-aryl(hetaryl)methyli-
dene-N-(2-nitroguanidino)amines X, XII, and XIII.
Obviously, the driving force of the transformation
of the initially formed adducts into azomethines was
elimination of the resonance-stabilized anions of
nitroacetic ester (or nitroacetophenone) along with
favorable energetics of the final conjugated products.
Physical characteristics of the obtained aryl(hetaryl)
methylideneguanidinoamines XI–XIII coincided with
those of model compounds prepared by authentic
synthesis from the corresponding aromatic aldehydes
and 1-amino-2-nitroguanidine; the mixing test did not
reveal any melting point depression.
Strong absorption bands at λmax of 328–337 nm
(ε = 28000–33000 L mol–1 cm–1) observed in electronic
absorption spectra of XI–XIII were characteristic of
chromophore system of such compounds [5, 7].
1H NMR spectrum of a mixture of XIV and XV
contained the proton signals of the both compounds.
The doublet signals at 6.06–7.79 ppm, characteristic of
the HB, NHX, HA multispin system of two dia-
stereomers a and b (in the ratio of 3.4 : 1), were
assigned to the adduct XIV. Broadened proton signals
of the primary (7.58 and 8.54 ppm) and secondary
(9.32 and 9.37 ppm) amino groups of nitroguanidine
fragments of the two diastereomers were found in the
weak-field part of the spectrum. The protons of =CH,
NH2, and NH groups of XV resonated at 8.19, 8.91–
8.94, and 4.12 ppm, respectively.
EXPERIMENTAL
Structures of the obtained compounds were con-
1
firmed by H NMR, IR, and electronic absorption
1H NMR spectra were recorded with the Jeol
ECX400A spectrometer (DMSO-d6, 399.78 MHz;
residual solvent protons as internal reference). IR
spectra were registered with the Shimadzu IRPrestige-
spectroscopy. The spectral data of X and XV coincided
with those of the same compounds synthesized
independently [5].
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 84 No. 8 2014

1498
EFIMOVA et al.
21 Fourier-spectrometer (KBr). Electronic spectra
were recorded with the Shimadzu UV-2401 PC spectro-
photometer (ethanol, quartz cell, l = 0.1 cm, c ≈
0.3 mmol/L). Elemental analysis was performed with
the EuroVector EA 3000 analyzer (CHN Dual mode).
ppm: 6.95 d and 7.77 d (4Н, 4-CH3OC6H4, J 8.8 Hz),
8.06 s (1Н, =CH), 8.43 s and 8.74 s (2H, NH2), 11.69 s
(1H, NH). Electronic absorption spectrum, λmax, nm
(ε): 332 (33000). Found, %: C 45.56; H 29.53; N 4.64.
С9Н11N5O3. Calculated, %: C 46.14; H 29.73; N 4.70.
1-Amino-2-nitroguanidine I was prepared as de-
b. A solution of 0.17 g (1.5 mmol) of 1-amino-2-
nitroguanidine I in 10 mL of water was added to a
solution of 0.2 g (1.5 mmol) of 4-methoxy-
benzaldehyde in 10 mL of ethanol. The mixture was
stirred at 80°C during 5 min and then cooled down.
The precipitated crystals were filtered off. Yield 0.33 g,
mp 202–203°C (ethanol–water, 2 : 1). The mixing test
with the sample obtained via the method a did not
reveal any depression of the melting point.
scribed elsewhere [8].
gem-Ethoxycarbonylnitroethenes II, III [9], IV,
and V [10]; gem-benzoylnitroethenes VII [11], VIII,
and IX [12] were prepared via condensation of
aldehydes with ethyl nitroacetate [13] or nitro-
acetophenone [14] upon heating in benzene in the
presence of acetic acid and β-alanine in a flask
equipped with the Dean–Stark trap. 1-Nitro-2-(4-
nitrophenyl)-1-ethoxy-carbonylethene VI was synthe-
sized via condensation of nitroacetic ester with N-(4-
nitro-phenylmethylidene)-n-butylamine [15].
N-(2-Nitroguanidino)-N-(2-thienylmethylidene)-
amine (XII). a. Prepared similarly to compound X,
method a from 0.32 g (1.4 mmol) of 1-nitro-2-(2-
thienyl)-1-ethoxycarbonylethene IV and 0.17
g
N-Benzylidene-N-(2-nitroguanidino)amine (X).
a. A solution of 0.27 g (2.2 mmol) of 1-amino-2-nitro-
guanidine I in 10 mL of water was added to a solution
(1.4 mmol) of 1-amino-2-nitroguanidine I. Yield 0.23 g
(73%), mp 189–192°C (ethanol–water, 2 : 1). IR
spectrum, ν, cm–1: 1338, 1440 (N–NO2), 1620, 1635
of 0.55
g
(2.2 mmol) of 1-nitro-2-phenyl-1-
1
(C=N), 3222, 3343, 3438 (NH). Н NMR spectrum, δ,
ethoxycarbonylethene II in 20 mL of ethanol. The
reaction mixture was stirred at 40°C during 40 min and
then cooled to 18–20°C. The precipitated crystals were
filtered off, washed sequentially with water, ethanol,
and diethyl ether, and dried in air. Yield 0.36 g (80%),
mp 182–183°C (ethanol–water, 2 : 1) (mp 182–185°C
[5]). Found, %: C 47.05; H 4.50; N 34.17. C8H9N5O2.
Calculated, %: C 46.37; H 4.34; N 33.81.
ppm: 7.10 d.d (1Н, C4H3S, J 5.0, J 3.6 Hz), 7.49 d.d
(1Н, C4H3S, J 3.6, J 1.1 Hz), 7.69 d.d (1Н, C4H3S, J
5.0, J 1.1 Hz), 8.30 s (1Н, =CH), 8.11 s and 8.76 s
(2H, NH2), 11.81 s (1H, NH). Electronic absorption
spectrum, λmax, nm (ε): 337 (28000). Found, %: C
33.80; H 32.85; N 3.31. С6Н7N5O2S. Calculated, %: C
34.00; H 32.11; N 2.94.
b. Prepared similarly to compound X, method b
from 0.34 g (1.5 mmol) of 1-benzoyl-1-nitro-2-(2-
thienyl)ethene VIII and 0.17 g (1.5 mmol) of 1-amino-
2-nitroguanidine I. Yield 0.25 g (78%), mp 189–191°C
(ethanol–water, 2 : 1).
b. A solution of 0.27 g (2.2 mmol) of 1-amino-2-
nitroguanidine I in 10 mL of water was added a
solution of 0.52 g (2.2 mmol) of 1-benzoyl-1-nitro-2-
phenylethene VII in 20 mL of ethanol. The reaction
mixture was stirred at 40°C during 40 min and then
cooled to 18–20°C. The precipitated crystals were
filtered off, washed sequentially with water, ethanol,
and diethyl ether, and dried in air. Yield 0.38 g (85%),
mp 183–184°C (ethanol–water, 2 : 1). The mixing test
with the sample obtained via the method a did not
reveal any depression of the melting point.
c. Prepared similarly to compound XI, method b
from 0.16 g (1.5 mmol) of thiophene-2-carbaldehyde
and 0.17 g (1.5 mmol) of 1-amino-2-nitroguanidine I.
Yield 0.30 g (95%), mp 190–192°C (ethanol–water,
2 : 1). The mixing test did not reveal any depression of
the melting point.
N-(4-Methoxyphenylmethylidene)-N-(2-nitrogua-
nidino)amine (XI). a. Prepared similarly to compound
X, method a from 0.4 g (1.6 mmol) of 2-(4-methoxy-
phenyl)-1-nitro-1-ethoxycarbonylethene III and 0.19 g
(1.6 mmol) of 1-amino-2-nitroguanidine I. Yield 0.35 g
(92%), mp 201–203°C (ethanol–water, 2 : 1). IR
spectrum, ν, cm–1: 1313, 1426 (NNO2), 1619, 1633
N-(2-Nitroguanidino)-N-(2-furylmethylidene)-
amine (XIII). a. Prepared similarly to compound X,
method a from 0.29 g (1.4 mmol) of 1-nitro-2-(2-
furyl)-1-ethoxycarbonylethene V and 0.167 g (1.4
mmol) of 1-amino-2-nitroguanidine I. Yield 0.22 g
(81%), mp 203–205°C (ethanol–water, 2 : 1). IR
spectrum, ν, cm–1: 1328, 1430 (N–NO2), 1612, 1622
1
1
(C=N), 3206, 3363, 3477 (NH). Н NMR spectrum, δ,
(C=N), 3218, 3345, 3443 (NH). Н NMR spectrum, δ,
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 84 No. 8 2014

REACTIONS OF 1-AMINO-2-NITROGUANIDINE
ppm: 6.62 d.d (1Н, C4H3O, J 1.7, J 3.4 Hz), 7.03 d
1499
REFERENCES
(1Н, C4H3O, J 3.4 Hz), 7.83 d (J 1.7 Hz), 8.05 s (1Н,
=CH), 8.22 s and 8.75 s (2H, NH2), 11.79 s (1H, NH).
Electronic absorption spectrum, λmax, nm (ε): 328
(29600). Found, %: C 36.54; H 3.55. С6Н7N5O3.
Calculated, %: C 37.03; H 3.61.
1. Mashkovskii, M.D., Lekarstvennye sredstva (Drugs),
Moscow: RIA “Novaya Volna,” 2012.
2. Granik, V.G., Osnovy meditsinskoi khimii (Funda-
mentals of Medicinal Chemistry), Moscow: Vuzovskaya
Kniga, 2001, p. 291.
3. Granik, V.G. Lekarstva (farmakologicheskii, biologi-
b. Prepared similarly to compound X, method b
from 0.36 g (1.5 mmol) of 1-benzoyl-1-nitro-2-(2-
furyl)ethene IX and 0.17 g (1.5 mmol) of 1-amino-2-
nitroguanidine I. Yield 0.23 g (78%), mp 204–205°C
(ethanol–water, 2 : 1).
cheskii
i khimicheskii aspekty) [Drugs (Pharma-
cological, Biological and Chemical Aspects)], Moscow:
Vuzovskaya Kniga, 2006, p. 209.
4. Zhaohai, Q., China Patent 2216324 А1, 2010.
5. Efimova, T.P., Ozerova, O.Yu., Belik, I.V., Noviko-
va, T.A., and Berestovitskaya, V.M., Rus. J. Gen.
Chem., 2012, vol. 82, no. 8, p. 1409. DOI: 10.1134/
S1070363212080129
6. Morozova, N.S., Metelkina, E.L., Novikova, T.A.,
Shlyapochnikov, V.A., Sergienko, O.I., and Perekalin, V.V.,
Zh. Org. Khim., 1983, vol. 19, no. 6, p. 1228.
7. Novikova, T.A., Metelkina, E.L., Efimova, T.P.,
Zaskokina, D.V., and Berestovitskaya, V.M., Russ. J.
Org. Chem., 2005, vol. 41, no. 6, p. 938. DOI: 10.1007/
s11178-005-0271-2.
c. Prepared similarly to compound XI, method b
from 0.14 g (1.5 mmol) of furfural and 0.17 g
(1.5 mmol) of 1-amino-2-nitroguanidine I. Yield 0.28 g
(95%), mp 203–205°C (ethanol–water, 2 : 1). The
mixing test did not reveal any depression of the
melting point.
Ethyl
2-nitro-3-(2-nitroguanidinoamino)-3-(4-
nitrophenyl)propanoate (XIV) and N-(2-nitro-
guanidino)-N-(4-nitrophenylmethylidene)amine (XV).
A solution of 0.12 g of 1-amino-2-nitroguanidine I in
10 mL of water was added to a solution of 0.26 g of 1-
nitro-2-(4-nitrophenyl)-1-ethoxycarbonylethene VI in
20 mL of ethanol. The reaction mixture was stirred at
40°C during 30 min and then cooled to 18–20°C. The
precipitated crystals were filtered off, washed
sequentially with water, ethanol, and diethyl ether, and
dried in air to yield 0.16 g of a mixture of XIV and XV
in the ratio of 1 : 1 (1H NMR). After recrystallization
from ethanol, only compound XV was isolated, mp
241–243°C (ethanol–water, 2 : 1) (mp 240–242°C [5]).
Found N, %: 32.57. C8H8N6O4. Calculated N, %:
33.33.
8. Henry, R.A., Makovsky, R.C., and Smith, G.B.L., J. Am.
Chem. Soc., 1951, vol. 73, no. 1, p. 474. DOI: 10.1021/
ja01145a513.
9. Baichurin, R.I., Baichurina, L.V., Aboskalova, N.I., and
Berestovitskaya, V.M., Russ. J. Gen. Chem., 2013,
vol. 83, no. 9, p. 1764. DOI: 10.1134/S1070363213090223.
10. Baichurina, L.V., Baichurin, R.I., Aboskalova, N.I. and
Berestovitskaya, V.M., Russ. J. Gen. Chem., 2010,
vol. 80, no. 10, p. 2022. DOI: 10.1134/
S1070363210100221.
11. Sokolov, N.A., Tishchenko, I.G., Karpitskaya, N.V.,
and Grinkevich, V.G., Vestn. BGU, 1978, Ser. 2, no. 3,
p. 29.
12. Berestovitskaya, V.M., Aboskalova, N.I., Ishmaeva, E.A.,
Bakhareva, S.V., Berkova, G.A., Vereshchagina, Ya.A.,
Fel’gendler, A.V., and Fattakhova, G.R., Russ. J. Gen.
Chem., 2001, vol. 71, no. 12, p. 1942. DOI: 10.1023/A:
1014200612456.
ACKNOWLEDGMENTS
13. Sintezy organicheskikh soedinenii (Synthesis of Organic
Compounds), Eds A.N. Nesmeyanov, P.A. Bobrov,
Moscow: Izd. Akad. Nauk SSSR, 1950, no. 1, p. 117.
Physico-chemical studies were performed in the
Center for Collective Use in Herzen State Pedagogical
University of Russia.
14. Long, L.M. and Troutman, H.D., J. Am. Chem. Soc.,
1949, vol. 71, no. 7, p. 2469. DOI: 10.1021/ja01175a067.
This work was financially supported by the
Ministry of Education of Russia in the frame of the
basic part of the governmental task.
15. Dornow, A. and Menzel, H., Lieb. Ann., 1954, vol. 588,
no. 1, p. 40. DOI: 10.1002/jlac.19545880105.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 84 No. 8 2014