Reactions of 2,4-disubstituted 5-nitro-1,2,3-triazole 1-oxides. 4. Dealkylation of 2-substituted 4,5-dinitro-1,2,3-triazole 1-oxides

Article abstract of DOI:10.1023/A:1025194031884

The N-dealkylation of 2-alkyl or 2-benzyl-substituted 4,5-dinitro-1,2,3-triazole 1-oxides has been studied. Conditions have been found for N-de-tert-butylation and 4-amino-5-nitro-1,2,3-triazole 1-oxide has been synthesized for the first time.

Full text of DOI:10.1023/A:1025194031884

Chemistry of Heterocyclic Compounds, Vol. 39, No. 5, 2003
REACTIONS OF 2,4-DISUBSTITUTED
5-NITRO-1,2,3-TRIAZOLE 1-OXIDES.
4*. DEALKYLATION OF 2-SUBSTITUTED
4,5-DINITRO-1,2,3-TRIAZOLE 1-OXIDES
T. I. Godovikova1, S. A. Vozchikova2, E. L. Ignat'eva2, L. I. Khmel'nitskii1,
and B. L. Korsunskii1
The N-dealkylation of 2-alkyl or 2-benzyl-substituted 4,5-dinitro-1,2,3-triazole 1-oxides has been
studied. Conditions have been found for N-de-tert-butylation and 4-amino-5-nitro-1,2,3-triazole 1-oxide
has been synthesized for the first time.
Keywords: substituted 4,5-dinitro-1,2,3-triazole 1-oxides, trifluoroperacetic acid, dealkylation.
1,2,3-Triazole 1-oxides containing no substituent at position 2 are of considerable interest as synthons,
since it is possible to carry out on them reactions known for 1,2,3- and 1,2,4-triazoles [2] such as salt formation,
addition to a multiple bond, nucleophilic substitution, etc. However our repeated attempts to obtain triazole
oxides of such structure by interacting the appropriate 3-nitrofuroxanes with ammonia according to the
recyclization reaction of the furoxane ring discovered by us [3-5] did not lead to the desired result. An
analogous route using aniline also failed to synthesize the corresponding oxides with a phenyl substituent in
position 2. Meanwhile it is known [6], that on nitration the latter is converted into a 2,4-dinitrophenyl
substituent, the elimination of which proceeds smoothly under the action of sodium methylate in methanol.
The present work is devoted to a study of the N-dealkylation of the available [7] 4,5-dinitro derivatives
of 1,2,3-triazole 1-oxides 1a-c with a methyl, ethyl, or benzyl substituent in position 2 respectively, using
reagents which are applied in analogous reactions for other classes of compound, such as potassium
permanganate [8], mercury acetate [9], sodium persulfate [10], potassium tert-butylate [11], dimethylformamide
[12], etc.
Numerous attempts to N-dealkylate compounds 1a-c did not lead to the target product. In the majority of
reactions either recovery or decomposition of the starting material was observed. Pure compounds were isolated
only in the case of dimethylformamide and sodium persulfate. Thus on interacting 2-methyl- and 2-benzyl-4,5-
dinitro-1,2,3-triazole 1-oxides 1a,c with dimethylformamide or sodium persulfate in the presence of silver
nitrate, fission of the N-oxide oxygen occurs, and the corresponding 2-substituted 4,5-dinitro-1,2,3-triazoles
2a,b are formed.
_______
* For Part 3 see [1].
__________________________________________________________________________________________
1
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 117913,
2
Russia; e-mail: ogv@cacr.ioc.ac.ru. Institute of the Problems of Chemical Physics, Russian Academy of
Sciences, Chernogolovka 142432, Moscow region. Translated from Khimiya Geterotsiklicheskikh Soedinenii,
No. 5, pp. 704-708, May, 2003. Original article submitted March 13, 2000; revision submitted October 13,
2000.
608
0009-3122/03/3905-0608$25.00©2003 Plenum Publishing Corporation

O2N
NO2
O2N
NO2
DMF / Na2S2O8
AgNO3
N
N
N
N
N
R
N
R
O
1a,c
2a,b
1a, 2a R = Me; 1c, 2b R = CH2Ph
Attempts to N-debenzylate 2-benzyl-4,5-dinitro-1,2,3-triazole 1-oxide (1c) with sodium persulfate in the
presence of copper chloride led to the nitrochloro- substituted benzyltriazole oxide 3. On the basis of the results
of elemental analysis and 14N NMR spectra of this product, in which there is one narrow signal at -31.90 ppm, it
may be concluded that there is one nitro group in this molecule. Comparison of the spectrum with the 14N NMR
spectrum of triazole oxide 1c containing signals of the 4- and 5-nitro groups at -34.39 (br) and -40.35 ppm
respectively [7] leads to the assumption that in the compound obtained the NO2 group is in position 4, i.e. it has
the structure 2-benzyl-5-chloro-4-nitro-1,2,3-triazole 1-oxide (3).
O2N
Cl
O2N
NO2
Na2S2O8
CuCl2
N
N
N
N
N
N
O
O
CH2Ph
CH2Ph
1c
3
Among the compounds of type 1 we also planned to study the dealkylation of a triazole oxide with a
tert-butyl group in position 2 (1d), considering that this substituent is more readily removable, for example on
saponification, than the methyl and ethyl groups in the series of esters and ethers [13-15]. Compound 1d was
presumed to be synthesized from 3,4-dinitrofuroxane by the scheme indicated below.
H2N
NO2
O2N
NO2
t-BuNH2
NH3
N
N
N
N
O
O
O
O
O2N
NO2
N
N
O
N
CMe3
1d
H2N
NO2
CF3COOOH
N
N
N
O
H2N
NO2
CMe3
4
N
N
N
H
5A
O
However on oxidizing 4-amino-2-tert-butyl-5-nitro-1,2,3-triazole 1-oxide (4) with trifluoroperacetic
acid, in place of the expected dinitro derivative 1d, 4-amino-5-nitro-1,2,3-triazole 1-oxide (5) in form A was
obtained in 50% yield, i.e. under the reaction conditions elimination of the tert-butyl group occurred
significantly more readily.
609

It must be noted that, on using trifluoroperacetic acid for the oxidation of 4-amino(alkylamino)-5-nitro-
1,2,3-triazole 1-oxides containing methyl, benzyl, or other substituents in position 2, no formation of
dealkylation products was observed in any experiment [7]. On the basis of the results obtained by us the
conclusion may be drawn that under such conditions only the tert-butyl group is removed from the molecule of
the appropriate triazole N-oxide with the same ease as on removing the tert-butyl protection from alcohols,
phenols, and thiols [16].
1
The structure of triazole oxide 5A was confirmed by data of elemental analysis, IR, UV, and H, 13C,
and 14/15N NMR spectra.
In the 15N NMR spectrum a large Overhauser effect on the 15N nuclei in the NH2 and N(2) (negative
signals) shows the presence of a direct N–H bond. Broadening of the signals of the N(2) and N(1) atoms probably
indicates intra- or intermolecular exchange with the low-populated form B containing NOH fragment.
H2N
NO2
5A
N
N
OH
N
5B
EXPERIMENTAL
1
The IR spectra were taken on a Specord IR 75 spectrophotometer in KBr tablets. The H, 13C, and
14/15N NMR spectra were obtained on a Bruker AM 300 instrument at frequencies of 300, 75.47, 21.67, and
30.42 MHz respectively, internal standard was TMS. The UV spectra were taken on a Specord UV instrument
in absolute ethanol. The mass spectra were obtained on a Varian instrument with direct insertion of the sample
into the ion source at an energy of ionizing electrons 70 eV, accelerating voltage was 1.75 kV, and emission
current 100 mA. Melting points were determined on a Boetius stage with a heating rate of 4°/min at the point of
melting. Column chromatography was carries out on silica gel L 100/250 µ, and TLC on Silufol UV 254 plates.
2-Benzyl-4,5-dinitro-1,2,3-triazole (2b). A solution of silver nitrate (0.2 g) in water (20 ml) was added
to a solution of triazole oxide 1c (0.2 g, 1.17 mmol) in acetonitrile (10 ml). The mixture was heated to 70-80°C
with vigorous stirring and a solution of sodium persulfate (0.2 g, 0.83 mmol) in water (20 ml) was added
dropwise to it. The reaction mixture was heated to 80-90°C and maintained at this temperature for 12-13 h, then
cooled to 20°C, water (50 ml) was added, and the mixture was extracted with ether (3 × 50 ml). The extract was
combined with the organic layer, dried with magnesium sulfate, and the solvent removed on a rotary evaporator.
Product 2b (0.06 g, 33%) was isolated from the residue by column chromatography (eluent CH2Cl2–CCl4, 2:3);
mp 73-75°C. After recrystallization from CCl4 it had mp 82-84°C, Rf 0.75 (CH2Cl2). IR spectrum, ν, cm-1: 1570,
1
1550, 1440, 1340, 1320, 1140, 1080, 960, 810, 730, 695. H NMR spectrum (acetone-d6), δ, ppm: 5.86 (2H, s,
CH2); 7.7 (5H, s, C6H5). 14N NMR spectrum (acetone-d6), δ, ppm: -33.02. The mass spectrum contains a peak for
the molecular ion M+ (m/z 249).
2-Benzyl-5-chloro-4-nitro-1,2,3-triazole 1-Oxide (3). A solution of copper(II) chloride (0.13 g,
0.76 mmol) in water (10 ml) was added to a solution of triazole oxide 1c (0.2 g, 0.76 mmol) in acetonitrile
(10 ml). The mixture was heated to 80°C with vigorous stirring and a solution of sodium persulfate (0.25 g,
1.04 mmol) in water (10 ml) was added dropwise to it. The reaction mixture was maintained at this temperature
for 20 h, then cooled to 20°C, and the organic layer separated. The aqueous layer was extracted with ether
(2 × 30 ml). The extract was combined with the organic layer, dried with magnesium sulfate, and the solvent
removed on a rotary evaporator. From the residue by column chromatography (CH2Cl2–CCl4, 1:1) were isolated
the starting material 1c (0.07 g, 38%), mp 121-122°C, Rf 0.7 (CH2Cl2) and product 3 (0.048 g, 24%),
mp 124-125°C, Rf 0.6 (CH2Cl2). IR spectrum, ν, cm-1: 2910, 1560, 1550, 1480, 1450, 1440, 1410, 1380, 1350,
610

14
1335, 1285, 1210, 1180, 1060, 885, 840, 790, 710, 690. N NMR spectrum (acetone-d6), δ, ppm: -31.90. The
mass spectrum contains peaks for the molecular ions (m/z 254 and 256). Found, %: C 42.60; H 2.85; Cl 14.03;
N 22.11. C9H7ClN4O3. Calculated, %: C 42.44; H 2.77; Cl 13.92; N 22.00.
tert
A saturated solution of ammonia in
4-Amino-2- -butyl-5-nitro-1,2,3-triazole 1-Oxide (4).
chloroform was added dropwise with stirring to a solution of 3,4-dinitrofuroxane [17] (1.7 g, 9.7 mmol) in
chloroform (30 ml) at -20 to -30°C. The progress of the reaction was followed by TLC (C2H4Cl2). After
disappearance of the starting material the temperature was raised to 0-5°C, a solution of tert-butylamine (1.0 g,
1.4 ml, 14 mmol) in ether (5 ml) was added, and the mixture was maintained at this temperature for 3-4 h until
disappearance of the aminonitrofuroxane. The inorganic solid was filtered off, and washed with chloroform
(2 × 20 ml). The chloroform extract was combined with the filtrate, washed with water (3 × 20 ml), and dried
with magnesium sulfate. The solvent was evaporated, and the residue (0.48 g, 25%) chromatographed on a
column (C2H4Cl2). Product 4 (0.32 g, 17%) of mp 151-152°C was obtained. IR spectrum, ν, cm-1: 3500, 3300,
3000, 2930, 1620, 1560, 1480, 1450, 1390, 1370, 1340, 1270, 1240, 1190, 1130, 1090, 1010, 900, 820, 800,
740. UV spectrum (EtOH), λ, nm: 220, 310, 379. Mass spectrum, m/z: 201 [M]+; 155 [M-NO2]+, 185 [M-O]+,
128 [M-O-t-Bu]+. Found, %: C 35.78; H 5.44; N 35.15. C6H11N5O3. Calculated, %: C 35.82; H 5.47; N 34.82.
4-Amino-5-nitro-1,2,3-triazole 1-Oxide (5). Triazole oxide 4 (0.2 g, 1 mmol) was added to a mixture
of trifluoroacetic acid (5 ml) and concentrated hydrogen peroxide (2 ml) at 0-10°C. The temperature of the
reaction mixture was raised to 18-20°C and maintained for ~3 h. The solid was then filtered off, washed with
trifluoro-acetic acid, with ether, and with acetone. Product 5 (0.058 g, 42%) was obtained having mp 77°C
(decomp.). IR spectrum, ν, cm-1: 3480, 3320, 2950, 1650, 1570, 1480, 1420, 1360, 1340, 1290, 1200, 1140,
1000, 800, 790, 740. UV spectrum, λ, nm: 208, 312.5, 370. 1H NMR spectrum (DMSO-d6), δ, ppm: 8.25 (2H, s,
NH2). 13C NMR spectrum (DMSO-d6), δ, ppm: 122.31 (C(5)), 148.02 (C(4)). 14N NMR spectrum (DMSO-d6),
δ, ppm: -29.92 (NO2). 15N NMR spectrum (DMSO-d6), δ, ppm: -30.20 (NO2); -57.88 (br, N(1)); -151.66 (br, N(2));
-318.15 (NH2). Found, %: C 16.78; H 2.12; N 48.43. C2H3N5O3. Calculated, %: C 16.55; H 2.07; N 48.27.
The authors are grateful to Candidate of Chemical Sciences Yu. A. Strelenko for taking and helping in
the interpretation of the NMR spectra.
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