Synthesis of 1-hydroxybenzotriazoles angularly annulated by furazan or furoxan rings

Article abstract of DOI:10.1007/s11172-009-0329-3

Synthesis of 6-hydroxy-6H-[1,2,3]triazolo[4,5-e][2,1,3]benzoxadiazole and a mixture of isomeric 6-hydroxy-6H-[1,2,3]triazolo[4,5-e][2,1,3]benzoxadiazole- 1(3)-oxides is carried out starting from 2,4-dinitrosoresorcinol. Total assignment of the signals in the ¹³C NMR spectra of O-methylated products of these compounds is performed.

Full text of DOI:10.1007/s11172-009-0329-3

Russian Chemical Bulletin, International Edition, Vol. 58, No. 11, pp. 2369—2375, November, 2009
2369
Synthesis of 1ꢀhydroxybenzotriazoles angularly annulated
by furazan or furoxan rings
V. A. Samsonov, G. E. Sal´nikov, and A. M. Genayev
N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry,
Siberian Branch of the Russian Academy of Sciences,
9 prosp. Akad. Lavrent´eva, 630090 Novosibirsk, Russian Federation.
Fax: 7 (383) 330 9752. Eꢀmail: Samson@nioch.nsc.ru
Synthesis of 6ꢀhydroxyꢀ6Hꢀ[1,2,3]triazolo[4,5ꢀe][2,1,3]benzoxadiazole and a mixture of
isomeric 6ꢀhydroxyꢀ6Hꢀ[1,2,3]triazolo[4,5ꢀe][2,1,3]benzoxadiazoleꢀ1(3)ꢀoxides is carried out
starting from 2,4ꢀdinitrosoresorcinol. Total assignment of the signals in the 13C NMR spectra
of Оꢀmethylated products of these compounds is performed.
Key words: nitrosophenols, 1ꢀhydroxybenzotriazoles, 2,1,3ꢀbenzoxadiazoles, 2,1,3ꢀbenzꢀ
1
oxadiazole Nꢀoxides, 2Hꢀbenzotriazole Nꢀoxides, H, 13C, 15N NMR spectroscopy.
1ꢀHydroxybenzotriazole is widely used as a promoter
in carbodiimideꢀbased1—3 and other methods for the synꢀ
thesis of peptides,4 nucleotides,5—7 and also in organic
synthesis.8,9 The use of this compound significantly
increases the yield and decreases racemization of the
reaction products. 1ꢀHydroxybenzotriazole derivatives
containing electronꢀwithdrawing groups in the ring
(trifluoromethyl, one or two nitro groups) are highly effiꢀ
cient and are also successfully used in organic synthesis,
in the synthesis of peptides and nucleotides.10,11
We synthesized 1ꢀhydroxybenzotriazoles annulated
by electronꢀwithdrawing heterocycles, namely, furazan
and furoxan, in the search for efficient promoters that can
be used in the synthesis of peptides, nucleotides and
in organic synthesis. Resorcinol (1) was used as the startꢀ
ing compound, its nitrosation leads to 2,4ꢀdinitrosoꢀ
resorcinol (2).12
it was found that only 5ꢀhydroxyꢀ4ꢀnitrosobenzofurazan
is formed in the reaction of the trioxime with acetic anhyꢀ
dride. It thus follows that trioxime 4 is the main oximation
product of compound 2. In fact, only one trioxime was
obtained by us upon treatment of compound 2 with
hydroxylamine hydrochloride in methanol (Scheme 1).
No other isomer was detected in the reaction mixture
judging by 1H NMR data.
Scheme 1
Taking into consideration that oꢀ and pꢀnitrosoꢀ
hydroxyarenes exist in tautomeric equilibrium with
quinone monooximes13 (nitroso compounds of this type
are obtained in both forms), the nitrosation products of
hydroxyarenes hereinafter will be referred to as the correꢀ
sponding nitroso compounds for the simplification of data
presentation.
NOH
The reaction of compound 2 with hydroxylamine
hydrochloride can result in two isomeric trioximes 3
and 4. It was claimed14 that isomer 3 was the main
product of this reaction, and compound 4 was presented
as an admixture. This conclusion was inferred from the
presumed formation of 7ꢀhydroxyꢀ4ꢀnitrosobenzofurazan
and small amount of 5ꢀhydroxyꢀ4ꢀnitrosobenzofurazan
upon reaction of the trioxime with acetic anhydride.
Later,15,16 these conclusions were shown to be erroneous,
Reagents and conditions: i. NaNO2, H2SO4; ii. NH2OH•HCl,
MeOH, reflux.
Synthesis of 1ꢀhydroxybenzotriazole fused with the
furazan ring was carried out according to Scheme 2. Treatꢀ
ment of compound 4 with acetic anhydride leads to
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2294—2299, November, 2009.
1066ꢀ5285/09/5811ꢀ2369 © 2009 Springer Science+Business Media, Inc.

2370
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 11, November, 2009
Samsonov et al.
Scheme 2
Ar = 2,4ꢀ(NO2)2C6H3
Reagents and conditions: i. Ac2O, 80—90 °C; ii. H+, MeOH, reflux; iii. 2,4ꢀDNPH, MeOH, HCl (gas), 20 °С; iv. MnO2, CHCl3,
50—55 °C; v. MeONa, MeOH, 40 °C.
to hydroxytriazolobenzofurazan 9. The structure of this
compound was established by analytical and spectral data.
Annulation of 1ꢀhydroxybenzotriazole by the furoxan
ring was carried out according to Scheme 3. Compound
10 is formed upon oxidation of compound 4 with MnO2
in acetonitrile in 70% yield.
5ꢀacetoxyiminodihydrobenzofurazanꢀ4ꢀone (5), hydrolyꢀ
sis of which results in 4ꢀhydroxyꢀ5ꢀnitrosobenzofurazan
6, which has been obtained earlier17 from 5ꢀnitrobenzoꢀ
furazan. Hydrazono oxime 7 is formed upon reaction of
compound 6 with 2,4ꢀdinitrophenylhydrazine (2,4ꢀDNPH).
It is known18 that oxidation of hydrazono oximes leads to
triazole Nꢀoxides. Triazolobenzofurazan 8 was obtained
by the oxidation of compound 7 with MnO2 in chloroꢀ
form in 80.4% yield. As has been shown earlier,19—23
2,4ꢀdinitrophenyl group in 2Hꢀbenzotriazoles is readily
eliminated under the action of nucleophilic reagents.
Treatment of compound 8 with sodium methoxide leads
Mass spectrum of this compound and the results of
elemental analysis corresponded to molecular formula
C6H3N3O2. The signals for two hydrogen atoms in the
1
form of doublets are observed in the H NMR spectrum
at δ 6.97 and 7.38 with SSCC 10.4 Hz, and a broadened
signal for one proton is observed at δ 5.56. The signals for
Scheme 3
Reagents and conditions: i. MnO2, acetonitrile, 20 °C; ii. 2,4ꢀDNPH, MeOH, HCl (gas), 20 °С; iii. МеONa, MeOH, 40 °C.

Synthesis of 1ꢀhydroxybenzotriazoles
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 11, November, 2009 2371
Table 1. Calculated and experimental (in DMSOꢀd6) chemical shifts of the carbon atoms of compounds 14, 15a, and 15b
Comꢀ
pound
Method
δ
C(3a)
C(4)
C(5)
C(5a)
C(8a)
C(8b)
ОМе
r2
*
14
Experiment
B3LYP/6Gꢀ31*
riB3LYP/L1
PBE/L2
Experiment
B3LYP/6Gꢀ31*
riB3LYP/L1
PBE/L2
Experiment
B3LYP/6Gꢀ31*
riB3LYP/L1
PBE/L2
149.6
154.7
151.8
154.5
113.2
119.9
114.8
114.1
152.3
156.7
151.6
150.8
117.4
123.4
121.3
122.5
114.6
119.8
117.3
117.9
119.0
126.0
124.4
126.4
118.3
118.9
117.9
119.1
114.5
113.5
112.7
114.8
118.5
118.4
116.7
116.8
128.7
133.5
132.0
133.4
129.5
134.9
133.1
134.5
127.2
131.8
130.5
132.6
141.8
145.0
143.4
145.9
145.0
146.2
143.8
143.7
104.9
108.1
102.8
100.7
129.6
135.2
134.4
136.8
130.6
136.2
135.8
138.5
127.6
133.1
131.5
132.1
69.6
71.5
70.4
71.2
69.3
71.4
70.3
71.1
69.3
71.5
70.2
71.0
—
0.995 (0.75)
0.996 (0.76)
0.995 (0.75)
—
0.986 (0.78, 0.38, 0.61)
0.989 (0.77, 0.35, 0.58)
0.984 (0.76, 0.34, 0.56)
—
0.993 (0.49, 0.32, 0.60)
0.987 (0.48, 0.31, 0.57)
0.973 (0.48, 0.28, 0.54)
15a
15b
* r is coefficient of correlation between calculated and experimental chemical shifts. Coefficient for the alternative signal
assigment, and also (in the case of compounds 15a and 15b) coefficients obtained with an assumption that signal sets
corresponding to these compounds are mixed up are given in the brackets.
six carbon atoms are observed in the 13C NMR spectrum
(Table 1), two of them are connected with hydrogen
atoms. The signals at δ 169.44, 153.36 and 150.45, apparꢀ
ently, correspond to the carbon atoms that are connected
with the nitrogen and oxygen atoms. The remaining
signal at δ 109.02 was assigned to the carbon atom that
is connected with the Nꢀoxide group. The presence of the
signal in the high field of the 13C NMR spectrum, which
corresponds to the carbon atom connected with the
Nꢀoxide group, is typical of benzofuroxans.24 These data
allow us to assign the structure of 4ꢀhydroxyꢀ5ꢀnitrosoꢀ
benzofuroxan to compound 10. In order to find out in
which form — quinonoid or nitrosophenol — compounds
6 and 10 exist, we recorded 15N NMR spectra. It is known
that chemical shifts of nitrogen atoms of the oxime and
the nitroso groups differ very much.25 5ꢀHydroxyiminoꢀ
4ꢀoxoꢀ4,5,6,7ꢀtetrahydrobenzofurazan А and 5ꢀhydroxyꢀ
iminoꢀ4ꢀoxoꢀ4,5,6,7ꢀtetrahydrobenzofuroxan B, which
have been synthesized by us earlier,26 were used as the
model compounds; the 15N NMR spectra for these comꢀ
pounds were also recorded. The NMR spectral data are
presented in Table 2. Three singlet signals for the nitrogen
atoms are observed in the 15N NMR spectra of all four
compounds. The lowꢀfield signals for N(1), apparently,
can be assigned to the nitrogen atom from oxime and
nitroso groups. Two rest signals N(2) and N(3) represent
the signals for the nitrogen atoms of the furazan and
furoxan rings. For furoxans, apparently, the highꢀfield
N(3) signals belong to the nitrogen atoms that are
connected with two oxygen atoms.24 Judging from the
15N NMR spectral data it can be concluded that comꢀ
pounds 6 and 10 in DMSO exist in the quinone oxime
form. The proportion of the nitroso form, obviously, is
insignificant.
2,4ꢀDinitrophenylhydrazone 11 was obtained upon
reaction of compound 10 with 2,4ꢀDNPH, the oxidation
of this compound with MnO2 in acetonitrile afforded comꢀ
1
pound 12. Judging by H NMR spectral data, product 12
represents a mixture of two isomers 12a and 12b in the
ratio 2.9 : 1, which differ from each other in the position
of the Nꢀoxide oxygen atom of the furoxan ring.
The presence of two isomers is typical of furoxans,
especially those annulated by aromatic rings, and is caused
by easy isomerization of the furoxan ring.27 Treatment
of compound 12 with sodium methoxide gave a mixture
of isomeric hydroxytriazolobenzofuroxans 13а and 13b.
The ratio of isomers was 6 : 1 judging by 1H NMR
spectral data.
It is known28 that methylation of 1ꢀhydroxybenzoꢀ
triazole leads to a mixture of Nꢀ and Oꢀmethylated comꢀ
Table 2. Chemical shifts of the nitrogen atom
in the 15N NMR spectra (in DMSOꢀd6)
Compound
δ
N(1)
N(2)
N(3)
A
6
B
10
422.34
443.61
406.10
421.15
410.74
422.12
387.88
370.28
406.02
409.21
366.80
362.52

2372
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 11, November, 2009
Samsonov et al.
pounds. The reaction of compound 9 and a mixture 13а,b
with methyl iodide resulted in only Oꢀmethylated comꢀ
pounds 14 and 15а,b. The ratio of tautomers 15а : 15b was
6.7 : 1 judging by 1H NMR spectral data. (Scheme 4).
DFTꢀpotential without the HF term, such as PBE, is also
reasonable: the correlation with the experiment is only
slightly worse, while the laboriosuess and computation
duration (using PRIRODA program)33 are significantly
smaller. According to the calculations, compound 15а is
0.5—0.9 kcal mol–1 more stable than compound 15b, and
this is in accordance with the observed dominance of
isomer 15а in the mixture.
Scheme 4
Thus, we described the synthesis and the spectral
characteristics of 1ꢀhydroxybenzotriazoles annulated by
furazan or furoxan rings. The obtained compounds are
analogs of promoters that are widely used in the synthesis
of peptides, nucleotides and other organic compounds.
Experimental
IR spectra were recorded on a Bruker Vector in KBr
(concentration — 0.25%), the most intensive absorption bands
in the spectra are presented. 1H and 13C NMR spectra were
obtained on a Bruker AMꢀ400 spectrometer (400.13 (1H) and
100.61 MHz (13C)) and on a Bruker Avance DRXꢀ500 spectroꢀ
meter (500.13 (1H) and 125.77 MHz (13C)) in CDCl3 and
DMSOꢀd6 for 10% solutions at 25 °C. Chemical shifts were
measured relative to the solvent residual signals: CDCl3 (δH 7.24
and δ 76.90), DMSOꢀd6 (δ 2.50 and δ 39.50). Multiplicity
C
H
C
of signals in the 13C NMR spectra was determined in the
Jꢀmodulation mode (JMOD) and by 13C—1H correlations.
15N NMR spectra were recorded on a Bruker Avance III 600
spectrometer (60.82 MHz). Chemical shifts were measured
relative to NH3 as the external standard. Mass spectra were
obtained on a Finnigan MATꢀ8200 mass spectrometer (ionizing
electron energy 70 eV, direct inlet of the sample, ion source
temperature 180 °C). The course of the reactions and purity of
the compounds were monitored by TLC on Sorbfil UVꢀ254
plates with visualization by UV light and iodine vapor. Comꢀ
pound 2 was synthesized by the known method,12 using
manganous dioxide catalyst (Spec 6ꢀ09ꢀ01ꢀ718ꢀ87, Leningrad
plant "Krasnyi khimik"). Melting points were determined on a
Kofler heating stage. Elemental analysis was carried out in
the Laboratory of microanalysis of the Institute of Organic
Chemistry, Siberian Branch of the Russian Academy of Sciences.
Geometry optimization in the quantum chemical comꢀ
putations for compounds 14 and 15а,b was carried out by
DFT/B3LYP method (6Gꢀ31* basis set ((4s)/[2s] for H,
(10s4p1d)/[3s2p1d] basis for C, N, O), GAMESS program),34
riDFT/B3LYP method (L1 basis set (Λ01)35 ((6s2p)/[2s1p] for
H, (10s7p3d)/[3s2p1d] for C, N, O), PRIRODA program)37
and DFT/PBE method (see Ref. 36) (L2 basis set (Λ02)33
((8s4p2d)/[3s2p1d] for H, (12s8p4d2f)/[4s3p2d1f] for C, N, O),
PRIRODA program). Calculations of the chemical shifts was
carried out by GIAO/DFT/PBE method (L2 basis set, PRIRODA
program).
Assignment of the signals in the 1H and 13C NMR
spectra for compounds 14, 15а, and 15b was made using
13C—1H correlation with direct (HSQC)29 and longꢀrange
(HMBC)30 SSCC. The NMR methods in this case allow
determination of relative positions of carbon and hydroꢀ
gen atoms of the benzene rings of the examined comꢀ
pounds. However, the NMR spectral data permit alternaꢀ
tive assignment of the signal for the benzene rings atoms.
Besides, the assignment of signals in the NMR spectra of
compounds 15а and 15b was ambiguous. In order to elimiꢀ
nate these ambiguities, we carried out quantum chemical
calculations (DFT) of geometry and chemical shifts in
the 13C NMR spectra of compounds 14, 15а, and 15b; a
comparison of the experimental data with the calculꢀ
ated values for different assignments has been made (see
Table 1). It can be seen from the Table that only one
variant of assignment, which is in good agreement with
the experiment, exists for each of the studied compounds,
and it is this variant that conforms best of all to the literaꢀ
ture data24,31 on the chemical shifts of analogs. Somewhat
better correlation with experimental data in the case of
structure 15a,b is achieved when B3LYP potential is used,
which is not surpising, because this potential reproduces
well the furoxan geometric parameters.32 The use of the
Cyclohexꢀ5ꢀeneꢀ1,2,3,4ꢀtetrone 1,2,4ꢀtrioxime (4)14
.
A mixture of dinitrosoresorcinol 2 (84 g, 0.5 mol), hydroxylamine
hydrochloride (50 g, 0.72 mol), 50% aqueous ethanol (1 L) and
conc. HCl (10 mL) was refluxed for 2 h and cooled. The
precipitate was filtered off, washed sequentially with water
(300 mL), ethanol (100 mL), and ether (200 mL). Compound 4
was obtained (83 g, 90%), m.p. 210 °C (decomp., from ethanol)

Synthesis of 1ꢀhydroxybenzotriazoles
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 11, November, 2009 2373
1
(cf. Ref. 14: m.p. 210 °C with flash). H NMR (DMSOꢀd6), δ:
J = 8.8 Hz, J = 2.4 Hz); 9.03 (d, 1 H, J = 2.4 Hz). 13C NMR
(DMSOꢀd6), δ: 116.14 (CH); 119.72 (CH); 121.30 (CH); 129.67
(CH); 131.31 (CH); 124.53; 128.99; 131.83; 142.26; 143.58;
148.79; 150.57. UV (EtOH), λmax/nm (logε): 240 (3.90); 295
(4.10). MS, m/z (Irel (%)): 343 [M]+ (100), 327 (10), 313 (15),
237 (15).
7.15, 7.27 (both d, 1 H each, J = 10.0 Hz); 12.72, 13.40, 13.95
(all br.s, 1 H each, ОН).
5ꢀNitrosoꢀ2,1,3ꢀbenzoxadiazolꢀ4ꢀol (6) was synthesized by
the modified method.14 Compound 4 (210 g, 1.15 mol) was
added to acetic anhydride (750 mL) and the mixture was heated
to 80 °C with vigorous stirring, to the beginning of exothermic
reaction. The mixture was kept for 1 h at 80—90 °C with water
cooling. Acetic anhydride was distilled off in vacuo at ~15 Torr.
Water (400 mL) was added to the residue. The mixture was kept
for 3 h at ~20 °C for decomposition of acetic anhydride. The
precipitate that formed was filtered off, washed with water and
dried. 4,5ꢀDihydroꢀ2,1,3ꢀbenzoxadiazoleꢀ4,5ꢀdione 5ꢀ(Oꢀacetylꢀ
oxime) (5) was obtained (175 g, 73.5%), m.p. 142—143 °C (from
benzene) (cf. Ref. 23: m.p. 142—143 °C). Found (%): C, 46.12;
H, 2.90; N, 20.10. C8H5N3О4. Calculated (%): C, 46.38,
H, 2.43, N, 20.29. IR, ν/cm–1: 1721 (C=О); 1775 (C=О).
1H NMR (DMSOꢀd6), δ: 2.30 (s, 3 H, Me); 7.60 (s, 2 H, CH).
13C NMR (DMSOꢀd6), δ: 19.30 (Me); 120.67 (CH); 125.02
(CH); 149.87; 151.34; 151.75; 167.25 (C=О); 171.64 (C=О).
UV (EtOH), λmax/nm (logε): 233 (3.83).
6ꢀHydroxyꢀ6Hꢀ[1,2,3]triazolo[4,5ꢀе][2,1,3]benzoxadiazole
(9). To a suspension of compound 8 (3.43 g, 0.01 mol) in
methanol (80 mL), NaOCH3 (1.52 g, 0.03 mol) was added; the
mixture was stirred for 6 h at 35—40 °C, concentrated to dryness,
chloroform (50 mL) was added to the residue. The precipitate
was filtered off, washed thoroughly with chloroform, and dried.
The precipitate was dissolved in water (15 mL) and acidified
with 10% HCl to pH ~5, cooled, the precipitate that formed
was filtered off, washed with water, and dried. Compound 9
was obtained (1.25 g, 70.8%), m.p. 206—207 °C (decomp., from
water). Found (%): C, 40.50; H, 1.62; N, 39.90. C6H3N5О2.
Calculated (%): C, 40.69; H, 1.71; N, 39.54. IR, ν/cm–1: 1423;
1
1531; 1583; 1639. H NMR (DMSOꢀd6), δ: 7.79, 7.86 (both d,
1 H each, J = 9.2 Hz); 6.18 (br.s, 1 H, OH). 13C NMR
(DMSOꢀd6), δ: 116.00 (CH); 129.52 (CH); 128.77; 129.51;
141.99; 149.56. UV (EtOH), λmax/nm (logε): 234 (4.25); 283
(3.62). MS, m/z (Irel (%)): 177 [M]+ (49), 149 (66).
Methanol (600 mL) and HCl (2 mL) were added to comꢀ
pound 5 (175 g, 0.85 mol) in a 1 L flask. The mixture was
refluxed for 1 h until all the starting oxime disappeared from the
mixture (TLC, ethyl acetate—hexane, 1 : 1, Rf 0.42 (compound
5) and 0.54 (compound 6)). The solvent was evaporated,
chloroform (200 mL) was added to the residue, the precipitate
was suspended, filtered off, and dried. Compound 6 was obtained
(90 g, 48%), m.p. 184—186 °C (from ethanol) (cf. Ref. 17:
m.p. 185—187 °C). Found (%): C, 43.72; H, 1.90; N, 25.40.
C6Н3N3О3. Calculated (%): C, 43.64; H, 1.82; N, 25.45.
1H NMR (DMSOꢀd6), δ: 7.28, 7.53 (both d, 1 H each,
J = 10.4 Hz); 10.65 (br.s, 1 H, OH). 13C NMR (DMSOꢀd6), δ:
118.17 (CH); 124.41 (CH); 148.77; 149.84; 152.23; 172.47.
4,5ꢀDihydroꢀ2,1,3ꢀbenzoxadiazoleꢀ4,5ꢀdione 4ꢀ(2,4ꢀdinitroꢀ
phenylhydrazone) 5ꢀoxime (7). 2,4ꢀDinitrophenylhydrazine
(2.0 g, 10.1 mmol) was added to a solution of compound 6
(1.65 g, 0.01 mol) in methanol (300 mL). Dry HCl was bubbled
through the mixture with stirring at ~20 °C, the mixture
was kept for 8 h at ~20 °C. The precipitate that formed was
filtered off, washed with methanol, and dried. Compound 7
was obtained (3.05 g, 96.3%), m.p. 234 °C (decomp., from
ethanol). Found (%): C, 42.40; H, 1.95; N, 28.30. C12H7N7О6.
Calculated (%): C, 42.23; H, 2.06; N, 28.70. 1H NMR
(DMSOꢀd6), δ: 7.49, 7.72 (both d, 1 H each, J = 9.6 Hz); 8.29
(d, 1 H, J = 8.8 Hz); 8.60 (dd, 1 H, J = 8.8 Hz, J = 2.4 Hz); 8.94
(d, 1 H, J = 2.4 Hz); 13.58 (s, 1 H, NH); 14.48 (s, 1 H, OH).
5ꢀ(2,4ꢀDinitrophenyl)ꢀ5Hꢀ[1,2,3]triazolo[4,5ꢀе][2,1,3]ꢀ
benzoxadiazole 6ꢀoxide (8). To a suspension of hydrazone 7
(4.0 g, 11.6 mmol) in chloroform (400 mL), МnO2 (10 g) was
added; the mixture was stirred at 40—50 °C for ~12 h (until all
starting compound has disappeared, TLC monitoring). The
precipitate was filtered off and extracted with chloroform in a
Soxhlet extractor. The extract was concentrated to 50 mL, the
precipitate that formed was filtered off, washed with small volume
of chloroform, and dried. Compound 8 was obtained (3.20 g,
80.4%), m.p. 246—248 °C (from CHCl3). Found (%): C, 41.82;
H, 1.30; N, 28.90. C6H3N3О3. Calculated (%): C, 41.98;
H, 1.46; N, 28.57. IR, ν/cm–1: 1341; 1465; 1498; 1554; 1611.
1H NMR (DMSOꢀd6), δ: 7.90, 7.98 (both d, 1 H each,
J = 9.60 Hz); 8.34 (d, 1 H, J = 8.8 Hz); 8.88 (dd, 1 H,
4ꢀHydroxyꢀ5ꢀnitrosoꢀ2,1,3ꢀbenzoxadiazole 1ꢀoxide (10).
To a solution of trioxime 4 (2.0 g, 10.9 mmol) in acetonitrile
(200 mL), MnO2 (5 g) was added, the mixture was stirred for 6 h
at ~20 °C. The precipitate was filtered off, the filtrate was
concentrated. The residue was chromatographed on silica gel
(ethyl acetate) (Rf = 0.75 in ethyl acetate). Benzofuroxan 10 was
obtained (1.4 g, 70%), m.p. 162 °C (decomp., from ethanol).
Found (%): C, 39.90; H, 1.42; N, 23.00. C6H3N3О4. Calculꢀ
ated (%): C, 39.79; H, 1.67; N, 23.20; IR, ν/cm–1: 1620; 1705.
1H NMR (DMSOꢀd6), δ: 6.97, 7.38 (both d, 1 H each,
J = 10.4 Hz); 5.56 (br.s, 1 H, OH). 13C NMR (DMSOꢀd6), δ:
113.39 (CH); 123.53 (CH); 109.02; 150.45; 153.36; 169.44.
UV (EtOH), λmax/nm (logε): 250 (4.04); 280 (4.13); 370 (3.72).
MS, m/z (Irel (%)): 181 [M]+ (100), 165 (10), 151 (15).
2,1,3ꢀBenzoxadiazoleꢀ4,5ꢀdione 4ꢀ(2,4ꢀdinitrophenylhydrꢀ
azone) 5ꢀoxime 1ꢀoxide (11) was obtained similarly to compound
7. Yield 80%, m.p. 212—214 °C (from ethanol). Found (%):
C, 41.10; H, 2.09; N, 26.90. C12H7N7О7. Calculated (%):
C, 39.89; H, 1.94; N, 27.15. IR, ν/cm–1: 1340; 1490: 1510;
1
1595; 1610; 1620. H NMR (DMSOꢀd6), δ: 7.34, 7.65 (both d,
1 H each, J = 10.4 Hz); 8.25 (d, 1 H, J = 9.2 Hz); 8.63 (dd, 1 H,
J = 9.2 Hz, J = 2.4 Hz); 8.94 (d, 1 H, J = 2.4 Hz); 13.62 (s, 1 H,
NH); 14.30 (s, 1 H, OH).
5ꢀ(2,4ꢀDinitrophenyl)ꢀ5Hꢀ[1,2,3]triazolo[4,5ꢀе][2,1,3]ꢀ
benzooxadiazole 1(3),6ꢀdioxide (12) was synthesized similarly
to compound 8. Yield 78%, m.p. 232—234 °C (from HNO3,
1
d = 1.42 g cm–3). Based on H NMR data, a mixture of two
compounds in the ratio 1 : 2.9 was obtained. Found (%):
C, 40.18; H, 1.27; N, 27.68. С12Н5N7О7. Calculated (%):
C, 40.11; H, 1.39; N, 27.30. IR, ν/cm–1: 1348; 1543; 1616;
1
1637; 1467; 1498. H NMR (DMSOꢀd6), δ, main isomer: 7.45,
7.62 (both d, 1 H each, J = 9.6 Hz); 8.35 (d, 1 H, J = 8.8 Hz);
8.89 (dd, 1 H, J = 8.8 Hz, J = 2.8 Hz); 9.03 (d, 1 H, J = 2.8 Hz);
minor isomer: 7.73, 7.79 (both d, 1 H each, J = 9.6 Hz); 8.27 (d,
1 H, J = 8.8 Hz); 8.86 (dd, 1 H, J = 8.8 Hz, J = 2.8 Hz); 9.00 (d,
1 H, J = 2.8 Hz). 13C NMR (DMSOꢀd6), δ, main isomer:
104.72; 113.44 (CH); 116.09 (CH); 121.23 (CH); 125.21; 128.98;
129.62 (CH); 131.29 (CH); 132.70; 143.54; 145.11; 148.80;

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Samsonov et al.
minor isomer: 105.98; 118.05 (CH); 119.65 (CH); 121.44 (CH);
123.28; 128.58; 129.85 (CH); 131.13 (CH); 132.28; 143.44;
148.63, 152.63. MS, m/z (Irel (%)): 359 [M]+ (100), 343 (35),
329 (5), 313 (10), 299 (25).
6. O. Akihiro, S. Kohji, S. Mitsuo, Tetrahedron Lett., 2004,
363.
7. S. Bae, M. K. Lakshman, J. Am. Chem. Soc., 2007, 129, 782.
8. D. A. Conlon, A. DrahusꢀPaone, G.ꢀJ. Ho, B. Pipik,
R. Helmy, J. M. McNamara, Y.ꢀJ. Shi, J. M. Williams,
D. Macdonald, D. Deschênes, M. Gallant, A. Mastracchio,
B. Roy, J. Scheigetz, Org. Process Res. Dev., 2006, 10, 36.
9. L. Chaveriat, J. Stasik, J. Lalot, G. Demailly, D. Beaupere,
Synthesis, 2005, 2476.
10. C. B. Reese, Zh. PeiꢀZhuo, J. Chem. Soc., Perkin Trans. 1,
1993, 2291.
11. K. Seio, K. Komura, J.ꢀCh. Bologna, M. Sekine, J. Org.
Chem., 2003, 68, 3849.
12. A. I. Buseev, Sintezy novykh organicheskikh reagentov
dlya neorganicheskogo analiza [Synthesis of Novel Chemical
Reactants for Inorganic Analysis], Izdꢀvo MGU, Moscow,
1972, 198 pp. (in Russian).
13. E. Yu. Belyaev, B. V. Gidaspov, Aromaticheskie nitrozosoediꢀ
neniya [Aromatic Nitroso Compounds], Khimiya, Leningrad,
1989, 175 pp. (in Russian).
14. W. Borsche, H. Weber, Liebigs Ann. Chem., 1931, 489, 270.
15. A. S. Angeloni, D. Dal Monte, E. Sandri, G. Scapini,
Tetrahedron, 1974, 30, 3849.
16. A. S. Angeloni, V. Cere, D. Dal Monte, E. Sandri,
G. Scapini, Tetrahedron, 1972, 28, 303.
6ꢀHydroxyꢀ6Hꢀ[1,2,3]triazolo[4,5ꢀе][2,1,3]benzoxadiazole
1(3)ꢀoxide (13) was synthesized similarly to compound 9. Yield
82%, m.p. 186—188 °C (decomp., from ethanol). Based on
1H NMR data, a mixture of isomers in the ratio 6 : 1 was
obtained. Found (%): C, 37.11; H, 1.31; N, 36.85. C6H3N5О3.
Calculated (%): C, 37.31; H, 1.57; N, 36.27. IR, ν/cm–1: 1645.
1H NMR (DMSOꢀd6), δ, main isomer: 7.45, 7.61 (both d, 1 H
each, J = 9.2 Hz); minor isomer: 7.70, 7.76 (both d, 1 H each,
J = 9.2 Hz). 13C NMR (DMSOꢀd6), δ, main isomer: 112.70
(CH); 112.88; 114.99 (CH); 129.29; 130.07; 144.92; minor
isomer: 104.89; 117.33 (CH); 118.40 (CH); 127.05; 127.11;
152.17. UV (EtOH), λmax/nm (logε): 240 (3.99); 259 (3.96);
348 (3.86). MS, m/z (Irel (%)): 193 [M]+ (50), 177 (50), 165 (5),
135 (70).
6ꢀMethoxyꢀ6Hꢀ[1,2,3]triazolo[4,5ꢀе][2,1,3]benzoxadiazole
(14). Dichloromethane (20 mL), methyl iodide (4.26 g,
0.015 mol), and tetrabutylammonium bromide (0.1 g) were
added to a solution of compound 9 (0.91 g, 0.005 mol) in 5%
NaOH (15 mL). The mixture was vigorously stirred for 4 h at
~20 °C, the layers were separated. the organic layer was washed
with water, dried with MgSO4, and concentrated. The residue
was suspended in hexane, the precipitate was filtered off.
Compound 14 was obtained (0.88 g, 82%), m.p. 135—136 °C
(from ethanol). Found (%): C, 44.20; H, 2.31; N, 36.85.
C6H3N5О3. Calculated (%): C, 43.98; H, 2.64; N, 36.64.
IR, ν/cm–1: 1442; 1455; 1527; 1566; 2953; 3087. 1H NMR
(DMSOꢀd6), δ: 8.06, 8.13 (both d, 1 H each, Н(4), Н(5),
17. D. Dal Monte, E. Sandri, P. Mazzaracchio, Boll. Sci. Fac.
Chim. Ind. Bologna, 1968, 26, 165; Chem. Abstrs, 1969, 70,
115074q.
18. T. I. Godovikova, E. L. Ignat´eva, L. I. Khmel´nitskii, Khim.
Geterotsikl. Soedin., 1989, 147 [Chem. Heterocycl. Compd.
(Engl.Transl.), 1989, 113].
1
J = 9.6 Hz); 4.61 (s, 3 H, ОCH3); H NMR (CDCl3), δ: 7.64,
19. R. A. Renfrow, M. J. Strauss, S. Cohen, E. Buncel, Aust.
J. Chem., 1983, 36, 1843.
7.83 (both d, 1 H each, J = 9.6 Hz); 4.50 (s, 3 H). 13C NMR
(DMSOꢀd6) see Table 1. 13C NMR (CDCl3), δ: 68.12 (ОCH3);
116.21 (CH); 117.30 (CH); 123.68; 130.48; 141.76; 149.23.
UV (EtOH), λmax/nm (logε): 290 (3.68); 235 (4.24). MS, m/z
(Irel (%)): 191 [M]+ (15); 163 (55), 148 (18), 132 (30).
20. E. Buncel, J. M. Dust, Can. J. Chem., 1988, 66, 1712.
21. J. M. Dust, E. Buncel, Can. J. Chem., 1991, 69, 978.
22. V. A. Samsonov, L. B. Volodarskii, V. L. Korolev, G. Kh.
Khisamutdinov, Khim. Geterotsikl. Soedin., 1993, 1364 [Chem.
Heterocycl. Compd. (Engl. Transl.), 1993, 1169].
23. V. A. Samsonov, L. B. Volodarskii, V. L. Korolev, G. Kh.
Khisamutdinov, Khim. Geterotsikl. Soedin., 1994, 1432 [Chem.
Heterocycl. Compd. (Engl. Transl.), 1994, 1243].
24. L. I. Khmel´nitskii, S. S. Novikov, T. I. Godovikova, Khimiya
furoksanov. Stroenie i sintez [Chemistry of Furoxans. Structure
and Synthesis] 2nd izd., Nauka, Moscow, 1996, 382 pp. (in
Russian).
25. M. Witanowski, L. Stefaniak, H. Januszewski, S. Szymanski,
G. A. Webb, Tetrahedron, 1973, 29, 2833.
26. V. A. Samsonov, L. B. Volodarskii, Khim. Geterotsikl. Soedin.,
1991, 1408 [Chem. Heterocycl. Compd. (Engl. Transl.), 1991,
1135].
6ꢀMethoxyꢀ6Hꢀ[1,2,3]triazolo[4,5ꢀе][2,1,3]benzoxadiazole
1(3)ꢀoxide (15а,b) was synthesized similarly to compound 14.
Yield 76%. Based on 1H NMR, a mixture of isomers in the
ratio 6.7 : 1 was obtained. M.p. 133—134 °C (from CHCl3).
Found (%): C, 40.30; H, 2.44; N, 33.50. C6H3N5О3. Calculꢀ
ated (%): C, 40.58; H, 2.43; N, 33.81. IR, ν/cm–1 : 1550; 1599;
1
1627; 3089. H NMR for compound 15а (DMSOꢀd6), δ: 7.57,
7.76 (both d, 1 H each, H(4), H(5), J = 9.6 Hz); 4.43 (s, 3 H,
ОCH3). 1H NMR for compound 15b (DMSOꢀd6), δ: 7.91, 7.82
(both d, 1 H each, H(4), H(5), J = 9.6 Hz); 4.43 (s, 3 H, ОCH3).
13C NMR spectra see Table 1. UV (EtOH), λmax/nm (logε): 252
(4.02); 344 (3.88). MS, m/z (Irel (%)): 207 [M]+ (15); 179 (48);
149 (100).
27. L. I. Khmel´nitskii, S. S. Novikov, T. I. Godovikova, Khimiya
furoksanov. Reaktsii i primenenie [Chemistry of Furoxans.
Reactions and Applications], Nauka, Moscow, 1983, 311 pp.
(in Russian).
28. O. L. Brady, C. V. Reynold, J. Chem. Soc., 1928, 193.
29. A. G. Palmer III, J. Cavanagh, P. E. Wright, M. Rance,
J. Magn. Reson., 1991, 93, 151; L. E. Kay, P. Keifer,
T. Saarinen, J. Am. Chem. Soc., 1992, 114, 10663; J. Schleucher,
M. Schwendinger, M. Sattler, P. Schmidt, O. Schedletzky,
S. J. Glaser, O. W. Sorensen, C. Griesinger, J. Biomol. NMR,
1994, 4, 301.
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Received February 5, 2008;
in revised form July 8, 2009