2-nitroguanidine derivatives: X. Synthesis and nitration of 4-nitriminotetrahydro-1,3,5-oxadiazine and 2-nitriminohexahydro-1,3,5-triazine and their substituted derivatives

Article abstract of DOI:10.1134/S1070428007100041

A new synthetic procedure was developed to obtain 1-hydroxymethyl-2- nitroguanidine from 2-nitroguanidine and formaldehyde without catalyst. Reactions of 2-nitroguanidine and its 1-methyl-and 1-phenylsubstituted derivatives with formaldehyde and urotropin under acid catalysis resulted in 4-nitriminotetrahydro-1,3,5-oxadiazine and 2-nitriminohexahydro-1,3,5-triazine and their methyl-and phenyl-substituted derivatives, whose nitration with concn. HNO₃ in the presence of acetic anhydride and concn. H ₂SO₄ depending on the temperature conditions led to the formation of 4-nitrimino-3,5-dinitrotetrahydro-1,3,5-oxadiazine, 3-methyl-4-nitrimino-5-nitrotetrahydro-1,3,5-oxadiazine, 2-nitrimino-5- nitrohexahydro-1,3,5-triazine, and 1,3,5-trinitro-hexahydro-1,3,5-triazine-2- one.

Full text of DOI:10.1134/S1070428007100041

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2007, Vol. 43, No. 10, pp. 1437−1440. © Pleiades Publishing, Ltd., 2007.
Original Russian Text © E.L. Metelkina, 2007, published in Zhurnal Organicheskoi Khimii, 2007, Vol. 43, No. 10, pp. 1447−1450.
2-Nitroguanidine Derivatives: X.* Synthesis and Nitration
of 4-Nitriminotetrahydro-1,3,5-oxadiazine
and 2-Nitriminohexahydro-1,3,5-triazine and Their Substituted
Derivatives
E. L. Metelkina
St. Petersburg State Technological Institute, St. Petersburg, 198013 Russia
Received February 7, 2007
Abstract—A new synthetic procedure was developed to obtain 1-hydroxymethyl-2-nitroguanidine from 2-nitro-
guanidine and formaldehyde without catalyst. Reactions of 2-nitroguanidine and its 1-methyl- and 1-phenyl-
substituted derivatives with formaldehyde and urotropin under acid catalysis resulted in 4-nitriminotetrahydro-
1,3,5-oxadiazine and 2-nitriminohexahydro-1,3,5-triazine and their methyl- and phenyl-substituted derivatives,
whose nitration with concn. HNO3 in the presence of acetic anhydride and concn. H2SO4 depending on the tempera-
ture conditions led to the formation of 4-nitrimino-3,5-dinitrotetrahydro-1,3,5-oxadiazine, 3-methyl-4-nitrimino-
5-nitrotetrahydro-1,3,5-oxadiazine, 2-nitrimino-5-nitrohexahydro-1,3,5-triazine, and 1,3,5-trinitro-hexahydro-1,3,5-
triazine-2-one.
DOI: 10.1134/S1070428007100041
The reaction of 2-nitroguanidine with formaldehyde
under catalysis with alkali is known to result in
1-hydroxymethyl-2-nitro-guanidine [2]. However the
consideration of acid-base characteristics of the 2-nitro-
guanidine in the series of nitroamides and nitroamines
permitted a suggestion that the nucleophilicity of the
nitrogen in the molecule of 2-nitroguanidine is sufficient
for this reaction to occur also without catalyst. We
actually established that boiling of the 2-nitroguanidine
with a triple excess of formaldehyde water solution for
3–5 min provided a hydroxymethyl derivative of
2-nitroguanidine II in 85% yield.
add the formaldehyde to this site under conditions of
acid catalysis.
The experiments showed that the heating of com-
pounds I and II in 10% hydrochloric acid and excess
formaldehyde solution at 80–85°C led to the formation
of a heterocyclic compound, 4-nitriminotetrahydro-1,3,5-
oxadiazine (III). Under similar conditions the reaction
of 1-methyl- and 1-phenyl-2-nitroguanidine (IV and V)
with formaldehyde water solution gave rise to new
representatives of this series compounds, 3-methyl- and
3-phenyl-4-nitriminotetrahydro-1,3,5-oxadiazines (VI
and VII).
The intermediate products of these reactions are
evidently dihydroxymethyl derivatives A whose dehydra-
tion results in the cyclization.
Inasmuch as in the molecules of 2-nitroguanidine (I)
and 1-hydroxymethyl-2-nitroguanidine (II) a second, less
reactive nucleophilic site was present we attempted to
H
N
H
NHR
N CH2OH
10% HCl
+ CH2O
O2NN
O2NN
O2NN
O
_H2O
NH2
N CH2OH
N
R
R
I, II, IV, V
III, VI, VII
A
R = H (I,III), CH2OH (II), Me (IV,VI), Ph (V,VII).
*For Communication IX, see [1].
1437

METELKINA et al.
1438
Synthesized compounds III, VI, and VII are stable
(III) with concn. HNO3- in acetic anhydride at –2÷0°C
4-nitrimino-3,5-dinitrotetrahydro-1,3,5-oxadiazine (X)
formed in a good yield.
colorless crystalline substances, whose composition and
1
structure was confirmed by elemental analyses and H
1
NMR spectra. The character of H NMR spectra of
The nitration of 3-methyl-4-nitriminotetrahydro-
1,3,5-oxadiazine (VI) with concn. HNO3- in acetic
anhydride at –5°C gave 3-methyl-4-nitrimino-5-nitro-
tetrahydro-1,3,5-oxadiazine (XI) that was isolated as
hydrate.
compounds III, VI, and VII is similar for the spectra
contain the methylene group signals in the region 5.10–
5.32 ppm and downfield signals of the protons from the
NH groups in the oxadiazine ring at 9.35–10.13 ppm
It was presumable that analogously to the reaction
with formaldehyde the 2-nitroguanidine would take up
urotropin in hydrochloric acid medium.
Actually, it was experimentally established that
the reaction of 2-nitroguanidine (I) with urotropin in
concn. HCl at room temperature led to the formation of
2-nitriminohexahydro-1,3,5-triazine monohydrochloride
(VIII), and after heating the reagents in 18% hydrochloric
acid at 50–55°C for 3 h we isolated a compound which
was assigned the structure of nitrimine (IX) based on
the elemental analysis and 1H NMR spectrum.
The composition and structure of nitro compounds X
and XI were confirmed by elemental analyses and H
NMR spectra.
1
In the 1H NMR spectrum of compound X the signals
of methylene protons are present as singlets at δ 5.02
and 5.47 ppm, and in the spectrum of compound XI the
singlets of methyl and methylene protons appear at δ
3.02, 5.11, and 5.74 ppm with the integral intensity ratio
3:2:2 respectively. Besides at δ 3.55 ppm a signal of
protons from the water molecule appears as a singlet of
integral intensity equal 2.
The treating of 2-nitriminohexahydro-1,3,5-triazine
(IX) and its monohydrochloride VIII with nitrating
mixtures HNO3-–H2SO4 and HNO3–NH4NO3 provided
2-nitrimino-5-nitrohexahydro-1,3,5-triazine (XII).
1
In the H NMR spectrum of 2-nitriminohexahydro-
1,3,5-triazine (IX) in the downfield region appear three
singlets of amine protons at δ 8.49, 9.11, and 9.49 ppm
at the integral intensity ratio 1:1:1. In the upfield region
the methylene groups signals are observed at δ 5.13 and
4.60 ppm (2:2).
To prepare more nitrated analogs of compounds III,
VI–IX nitration procedures were developed by concn.
HNO3 in the presence of acetic anhydride and concn.
H2SO4.
H
N
As a result of investigations it was established that
the nitration of 4-nitriminotetrahydro-1,3,5-oxadiazine
O2NN
NH
N
H
NNO2
NNO2
O2N
NO2
H
HNO3
Ac2O
N
N
N
HN
NH
HNO3 H2SO4
O2NN
NNO2
O
X
O
III
N
H
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 10 2007

2-NITROGUANIDINE DERIVATIVES: X.
1439
The nitration of compound XII with concn. HNO3 in
acetic anhydride at 15–45°C yielded its analog of a higher
nitration degree, 1,3,5-trinitrohexahydro-1,3,5-triazin-2-
one (XIII).
precipitate was filtered off, washed with water, and dried
at 50–55°C. Yield: 0.56 g (51%), mp >300°C. 1H NMR
spectrum, δ, ppm: 5.10 s (4H, 2CH2), 9.35 s (2H, 2NH).
Found, %: C 24.28; H 4.02; N 38.49. C3H6N4O3.
Calculated, %: C 24.32; H 4.05; N 38.35.
H
N
Compounds VI and VII were similarly obtained.
3-Methyl-4-nitriminotetrahydro-1,3,5-oxadiazine
(VI). From 2.36 g (0.02 mol) of 1-methyl-2-nitro-
guanidine (IV) and 8 ml of 35% formaldehyde water
solution we obtained 2.02 g (63%) of compound VI, mp
O2NN
NNO2
N
H
O2N
N
N
1
HNO3 Ac2O
134–135°C (from water). H NMR spectrum, δ, ppm:
O
NNO2
3.10 s (3H, Me), 5.10 s (4H, 2CH2), 9.85 s (1H, NH).
Found, %: C 29.92; H 5.11; N 35.34. C4H8N4O3.
Calculated, %: C 30.00; H 5.00; N 35.00.
O2N
3-Phenyl-4-nitriminotetrahydro-1,3,5-oxadiazine
(VII). From 1.8 g (0.01 mol) of 1-phenyl-2-nitro-
guanidine (V) in 6 ml of 10% hydrochloric acid and
4 ml of 35% formaldehyde water solution we obtained
0.89 g (40%) of compound VII, mp 155–156°C (from
The composition and structure of nitro compounds
X–XIII were confirmed by elemental analyses and H
NMR spectra. Compounds X and XII were formerly
described [3], but the nitration conditions of compounds
III and VIII were not revealed.
1
1
water). H NMR spectrum, δ, ppm: 5.22 s (2H, CH2),
5.32 s (2H, CH2), 7.53 s (5H, Ph), 10.13 s (1H, NH).
Found, %: C 48.46; H 4.58; N 25.41. C9H10N4O3.
Calculated, %: C 48.65; H 4.54; N 25.23.
EXPERIMENTAL
1H NMR spectra were registered on spectrometers
Tesla BS-487C (80 MHz) and BrukerAC-200 (200 MHz)
in DMSO-d6, external reference HMDS.
2-Nitriminohexahydro-1,3,5-triazine monohydro-
chloride (VIII). To a dispersion of 2.5 g (0.024 mol) of
2-nitroguanidine in 11 ml of concn. HCl was added at
room temperature while stirring 2.6 g of urotropin. After
the halogenization of the mixture (2 h) the flask was
stoppered and put into a desiccator. After 3 days the
formed solid was dissolved in 50 ml of water. The crystals
precipitated on the next day were filtered off, washed
with ethanol, and dried at 30°C. Yield 4.2 g (96%), mp
176°C. Found, %: C 19.78; H 4.51; N 38.57.
1-Hydroxymethyl-2-nitroguanidine (II). To a dis-
persion of 2.08 g (0.02 mol) of 2-nitroguanidine in 8 ml
of water was poured 6 ml of 32% formaldehyde water
solution, then the mixture was brought to boiling. After
2–3 min the formed solution was cooled, the separated
amorphous precipitate was filtered off and recrystallized
from water. Yield 2.55 g (85%), mp 220°C. Found, %:
C 17.93; H 4.47; N 42.04. C2H6N4O3. Calculated, %:
C 17.91; H 4.48; N 41.79.
.
C3H7N5O2 HCl. Calculated, %: C 19.84; H 4.408; N 38.45.
2-Nitriminohexahydro-1,3,5-triazine (IX). To a dis-
persion of 2.08 g (0.02 mol) of 2-nitroguanidine in
80 ml of 18% hydrochloric acid was added at stirring 3 g
of urotropin in 7 ml of water, and the mixture was heated
for 3 h at 55°C. The solution obtained was evaporated
on a rotary evaporator. The colorless precipitate was
filtered off and recrystallized from water. Yield 2.2 g
(78%), t.decomp. 200–205°C. Found, %: C 24.78; H 4.84;
N 48.51. C3H7N5O2. Calculated, %: C 24.82; H 4.82;
N 48.27.
4-Nitriminotetrahydro-1,3,5-oxadiazine (III). a. To
a dispersion of 1.04 g (0.01 mol) of 2-nitroguanidine in
6 ml of 10% hydrochloric acid was added at stirring
4 ml of 35% formaldehyde water solution, and the
mixture was heated for 3 h at 80–85°C. On cooling the
separated precipitate was filtered off, washed with water,
and dried at 50–55°C. Yield 0.84 g (56%), mp >300°C.
Found, %: C 24.28; H 4.02; N 38.49. C3H6N4O3.
Calculated, %: C 24.32; H 4.05; N 38.35.
b. To a dispersion of 1 g (8 mmol) of reagent II in 6
ml of 10% hydrochloric acid was added at stirring 4 ml
of 35% formaldehyde water solution, and the mixture
was heated for 3 h at 80–85°C. On cooling the separated
4-Nitrimino-3,5-dinitrotetrahydro-1,3,5-oxa-
diazine (X).At 0°C to 2.2 g (0.02 mol) of acetic anhydrid
was added dropwise at stirring 1.5 ml (0.035 mol) of
concn. HNO3 (d 1.51 g/cm3). Then at –2°C within 5 min
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 10 2007

METELKINA et al.
1440
was added 0.5 g (3.5 mol) of reagent III which dissolved,
and 20 min later a precipitate separated that was in 1 h
filtered off, washed with cold water, and dried at 30–
5°C, and poured into ice water. In 2.5 h the separated
precipitate was filtered off, washed with cold water, and
dried. Yield 0.35 g (67%), mp.187–188°C (from water).
Found, %: C 19.16; H 3.28; N 44.62. C3H6N6O4.
Calculated, %: C 19.11; H 3.33; N 44.68.
1
40°C. Yield 0.48 g (56%), t.decomp. 85°C. H NMR
spectrum, δ, ppm: 5.20 s (CH2), 5.47 s (CH2). Found, %:
C 15.35; H 1.98; N 35.47. C3H4N6O8. Calculated, %:
C 15.25; H 1.69; N 35.59.
1,3,5-Trinitrohexahydro-1,3,5-triazin-2-one (XIII).
a. At 0°C to 2.7 g (0.025 mol) of acetic anhydride was
added 1.5 ml (0.035 mol) of concn. HNO3 (d 1.51 g/cm3),
then the mixture was heated to 45°C, and within 5 min
was added at stirring 0.5 g (3 mmol) of compound XII
that dissolved in 5–6 min, and within another 5 min
a precipitate separated. After 1 h the reaction mixture
was cooled to 10°C, the separated precipitate was filtered
off, washed thrice with cold dichloromethane, and dried.
Yield 0.32 g (53%), t.decomp. 173°C. 1H NMR spectrum,
δ, ppm: 5.4 s (CH2), 6.05 s (CH2). Found, %: C 15.12;
H 2.23; N 34.98. C3H6N7O4. Calculated, %: C 15.25;
H 1.69; N 35.59.
3-Methyl-4-nitrimino-5-nitrotetrahydro-1,3,5-
oxadiazine (XI). To 1.5 g (14 mmol) of acetic anhydride
was added at –5°C while stirring 0.6 ml (14 mmol) of
concn. HNO3 (d 1.50 g/cm3). To the solution obtained
was added at –5°C within 20 min 1.1 g (7 mmol) of
reagent VI. The mixture was stirred for 1.5 h at –5°C,
then it was poured into ice mixed with water, at 0–5°C
the formed precipitate was filtered off, washed with cold
water, and dried in air. Yield 0.98 g (70%), t.decomp.
108°C. Found, %: C 21.96; H 4.16; N 31.12.
.
C4H7N5O5 H2O. Calculated, %: C 21.53; H 4.04; N 31.38.
b To 2.7 g (0.025 mol) of acetic anhydride was added
at 0°C 1.5 ml (0.035 mol) of concn. HNO3 (d 1.51 g/cm3),
then the mixture was warmed to 24°C, and within 5 min
was added at stirring 0.5 g (3 mmol) of compound XII.
After 25–30 min a precipitate started to form that 2 h
later after cooling the reaction mixture to 5°C was filtered
off, washed with cold water, and dried. Yield 0.3 g (50%),
t.decomp. 173°C. Found, %: C 15.39; H 2.24; N 34.96.
C3H6N7O4. Calculated, %: C 15.25; H 1.69; N 35.59.
2-Nitrimino-5-nitrohexahydro-1,3,5-triazine (XII).
a. At 0°C to 1.8 ml of concn. HNO3 (d 1.51 g/cm3) was
added at stirring 5.4 ml of 95% H2SO4. To the nitrating
mixture at 0°C was added by small portions within 40
min 4.2 g (0.023 mmol) of 2-nitriminohexahydro-1,3,5-
triazine monohydrochloride (VIII), then the mixture was
warmed to 24°C and stirred at this temperature for 1 h.
The reaction mixture was afterwards poured into ice
water, the separated precipitate was filtered off, washed
with cold water, and dried. Yield 3.9 g (94%), mp 187°C.
Found, %: C 19.20; H 3.21; N 44.76. C3H6N6O4.
Calculated, %: C 19.11; H 3.33; N 44.68.
c. At 0°C to 2.7 g (0.025 mol) of acetic anhydride
was added 1.5 ml (0.035 mol) of concn. HNO3
(d 1.51 g/cm3), then the mixture was warmed to 15°C,
and within 5 min was added at stirring 0.5 g (3 mmol) of
compound XII. After 40–45 min a precipitate started to
form that 2 h later after cooling the reaction mixture to
5°C was filtered off, washed with cold dichloromethane,
and dried at room temperature. Yield 0.3 g (50%),
t.decomp. 173°C. Found, %: C 15.22; H 2.16; N 34.95.
C3H6N7O4. Calculated, %: C 15.25; H 1.69; N 35.59.
b. At 0°C to 1.25 ml of concn. HNO3 (d 1.51 g/cm3)
was added at stirring 3.75 ml of 95% H2SO4. To the
nitrating mixture at 0°C was added by small portions
within 10 min 1.44 g (8 mmol) of 2-nitriminohexahydro-
1,3,5-triazine (IX), then the mixture was warmed to 20–
25°C, and the reaction mixture was kept at this
temperature for 30–35 min. The reaction mixture was
afterwards poured into ice water, the separated precipitate
was filtered off, washed with cold water, and dried. Yield
The study was carried out under a financial support
of the International Science and Technology Center (grant
no. 2468p).
1
1.2 g (82%), mp 187°C (from water). H NMR spectrum,
δ, ppm: 4.87 s (CH2), 5.31 s (CH2), 9.14 s (NH), 9.22 s
(NH). Found, %: C 19.22; H 3.34; N 44.74. C3H6N6O4.
Calculated, %: C 19.11; H 3.33; N 44.68.
REFERENCES
c. To 10 ml of concn. HNO3 (d 1.51 g/cm3) was added
at stirring 5 g of ammonium nitrate, then at room
temperature 0.5 g of 2-nitriminohexahydro-1,3,5-triazine
monohydrochloride (VIII) was added. The reaction
mixture was stirred for 1 h at 55°C, then it was cooled to
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 10 2007