Synthesis of hetarylsulfanyl- and hetaryloxyfuroxans by nucleophilic substitution of nitro group in nitrofuroxans with heterocyclic thiol and hydroxy derivatives

Article abstract of DOI:10.1007/s10593-015-1678-5

[Figure not available: see fulltext.] We report a general method for the synthesis of previously unknown heterocyclic systems containing furoxan and heterocyclic fragments linked by S- and O-bridges, based on nucleophilic substitution of nitro group in 4-

Full text of DOI:10.1007/s10593-015-1678-5

DOI 10.1007/s10593-015-1678-5
Chemistry of Heterocyclic Compounds 2015, 51(2), 176–186
Synthesis of hetarylsulfanyl- and hetaryloxyfuroxans by
nucleophilic substitution of nitro group in nitrofuroxans
with heterocyclic thiol and hydroxy derivatives*
Leonid L. Fershtat1, Margarita A. Epishina1, Alexander S. Kulikov1,
Marina I. Struchkova1, Nina N. Makhova1*
1 N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky Ave., Moscow 119991, Russia; е-mail: mnn@ioc.ac.ru
Translated from Khimiya Geterotsiklicheskikh Soedinenii,
2015, 51(2), 176–186
Submitted January 13, 2015
Accepted January 28, 2015
We report a general method for the synthesis of previously unknown heterocyclic systems containing furoxan and heterocyclic fragments
linked by S- and О-bridges, based on nucleophilic substitution of nitro group in 4-nitrofuroxans with HetS and HetO groups introduced
by reactions with hetarylthiols and hydroxy heterocycles in 1,8-diazabicyclo[5.4.0]undec-7-ene/МеCN system at room temperature. We
showed that hetarylthiols reacted with 4-nitrofuroxans containing aliphatic, benzyl, and aromatic substituents at the ring С-3 atom,
allowing to obtain a library of previously unknown hetarylsulfanylfuroxans, while the reaction with hydroxy heterocycles was successful
only in the case of 4-nitro-3-phenylfuroxan, the rest of the nitrofuroxans showing low reactivity, and substitution products could be
obtained only in certain cases. 4-Nitrofuroxans with electron-withdrawing substituents (NO2, CONH2) acted as oxidants, forming
1,2-di(hetaryl)disulfides.
Keywords: hetaryloxyfuroxans, hetarylthiols, hydroxyheterocycles, 4-nitrofuroxans, disulfide bridges, hetarylsulfanylfuroxan library,
nucleophilic substitution.
At the end of the 20th century it was established that
nitric oxide (NO) is one of ubiquitous and crucial regulator
molecules for cellular metabolism, affecting various
physiological and pathophysiological processes. Nitric
oxide participates in the regulation of vasoconstriction,
inhibits thrombocyte aggregation and adhesion to blood
vessel walls, acts on the central and autonomic nervous
systems, regulating respiratory, digestive, urinary and
reproductive functions.2–11
Therefore, one of the most active areas of medicinal
chemistry is the search for compounds capable of releasing
NO in the body, either enzymatically, or independently of
NO synthases. Several drugs are currently available that act
by releasing NO (exogenous NO), first of all, nitrates,
nitrate esters, and nitrites (nitroglycerin, nitrosorbide,
isosorbide mononitrate, amyl nitrite, etc.), which are used
as vasodilators. Many different types of compounds have
been synthesized and tested as NO donors (guanidines,
nitramines, oximes, mesoionic systems, heterocyclic
N-oxides, and others).12,13 1,2,5-Oxadiazole 2-oxides
(furoxans) are also known as compounds capable of NO
release in vivo.14–16
One of the approaches to the preparation of new
pharmacologically active compounds involves the addition
of a furoxan ring as potential NO donor to molecules with
known pharmacological activity. Such a strategy has been
widely used by the Italian chemist A. Gasco with positive
results.17–19 Thus, the goal of our current work was the
development of a general method for the synthesis of
previously unknown heterocyclic systems, with sulfur or
oxygen linkers connecting a furoxan system to various
heterocyclic pharmacophores.
Recently we developed a new, simple and effective
method for the synthesis of previously practically
* A brief report is available.1
0009-3122/15/5102-0176©2015 Springer Science+Business Media New York
176

Chemistry of Heterocyclic Compounds 2015, 51(2), 176–186
Scheme 1
HetSH
2a–n
S Het
NO2
SHet
R
NO2
R
NO2
S Het
R
R
N
N
DBU, MeCN, rt
– [DBUH]
N
N
N
N
N
N
– NO2
O
O
N
O
O
O
O
O
O
1a,b
3a–ab
O
O
Het
O
O
N
HetSH
2a–n
N
NO2
S
N
N
N
O
N
DBU, MeCN, rt
O2N
S
N
Het
O
O
O
1d
3ac–ap
R2
N
R3
R3
N
N
N
2l m 3c g r ab an ao
, , ,
2n 3d h ap
, , , Het =
2a–k, 3a,b,e,f,i–q,s–am Het =
;
,
,
,
,
Het =
;
N
N
H2N
N
S
N
R1
1a, 3a–c,i–r R = Ph; 1b, 3e–h,s–ab R = Bn;
1
1
1
1
1
2a 3a e ac
2b j k 3b f p q z aa ad al am
2c 3i s ae
, , R = Et;
2h 3n x aj
, , , R = CH2CH2Ph;
2d 3j t af
2e 3k u ag
,
, , R = H; , , , , , , , ,
,
,
,
R = Me;
,
,
, , R = n-Pr;
,
, , R = i-Pr;
1
1
1
1
2f 3l v ah
, , , R = n-Bu;
2g 3m w ai
2i 3o y ak
, , R = All;
,
,
,
R = Bn;
,
2a–i, 3a,b,e,f,i–o,s–y,ac R2 = H; 2j, 3p,z,al R2 = NO2; 2k, 3q,aa,am R2 = Br; 2l, 3c,g,an R3 = NH2; 2m, 3r,ab,ao R3 = Me
unavailable 3-alkyl- and 3-aryl-4-nitrofuroxans 1a,b,d,
enabling the preparation of these compounds in significant
quantities.20 Therefore, in this work we planned to perform
nucleophilic substitution of nitro group with hetaryl-
sulfanyl and hetaryloxy fragments by treating 4-nitro-
furoxans with hetarylthiols and hydroxy derivatives of
heterocycles in the presence of bases.
reaction media: KOH/DMF, K2CO3/DMF, K2CO3/acetone,
Et3N/MeCN, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)/
MeCN, DBU/[bmim]BF4, [bmim]OH/DMF, and [bmim]
OH/[bmim]BF4 ([bmim]–butylmethylimidazolium). The first
representative of hetarylsulfanylfuroxans 3a was obtained
only in the DBU/MeCN system at room temperature in
65% yield. These optimized conditions were used for the
preparation of several additional hetarylsulfanylfuroxan
representatives 3b–h from nitrofuroxans 1a,b and thiols
2a,b,l,n (Scheme 1).1
In the first experiments, we used hetarylthiols 2, while
the starting 4-nitrofuroxans contained phenyl, benzyl,
aliphatic, and various electron-withdrawing substituents at
the С-3 atom of 1,2,5-oxadiazole ring: Ph (compound 1a),
Bn (compound 1b), NO2 (compound 1с), 4-nitro-3-[6-(4-nitro-
furoxan-3-yl)hexyl] (compound 1d), and CONH2
(compound 1e), which were synthesized according to known
procedures.20–22 The heterocyclic thiols 2a–m have been
described in the literature,23–25 while the thiol 2n is
commercially available. All the investigated thiols 2а–n
possess some types of pharmacological activity. Thus,
derivatives of indolotriazinethiols 2a–k have been
characterized as a new series of compounds with pronounced
antiparasitic23 and antihypoxic26 activity. The diamino-
pyrimidinethiol 2l in combination with gold nanoparticles
shows a wide range of antibacterial activity,27 dimethyl-
pyrimidinethiol 2m may serve as an effective inhibitor of
certain metal-containing enzymes,28 while 5-amino-1,3,4-thia-
diazole-2-thiol 2n is a strong inhibitor of carbonic anhydrase
IX, and thus a potential anticancer agent.29
As a part of this study, we were interested in evaluating
the reactivity of 4-nitrofuroxans 1a–e towards nucleophilic
substitution of nitro group with hetarylsulfanyl and
hetaryloxy fragments, depending on the structure of
substituents at the C-3 atom of furoxan ring and the type of
heterocyclic fragment in the starting nucleophiles. We
previously demonstrated the general possibility of nitro
group substitution in 4-nitrofuroxans with heterocyclic
thiols,1 using the model reaction of 4-nitro-3-phenylfuroxan
(1а) with triazinethiol 2а. In order to find the optimum
conditions for this process, we used various bases and
The nucleophilic substitution of nitro group in
nitrofuroxans with HetS fragments can be formally
considered as nucleophilic aromatic substitution according
to SNAr mechanism. However, the formation of
Meisenheimer-type complex in furoxan ring is unlikely,
because both double bonds in the ring are strictly fixed,
while the О(1)–N(2) bond is close to ordinary.30 We can
assume that the negative charge arising after attack by
thiolate ion at the nitrofuroxan С-4 atom is localized on the
ring N-5 atom, followed by elimination of NO2 anion and
formation of the final hetarylsulfanylfuroxan 3 (Scheme 1).
An analogous mechanism was proposed by us earlier.31
As previously shown,1 the substitution of nitro group in
4-nitro-3-phenylfuroxan (1а) occurred faster and with
higher yields than in 3-benzyl-4-nitrofuroxan (1b). In
contrast to furoxans 1a,b, the nucleophilic substitution in
3,4-dinitrofuroxan (1с) could be achieved only with thiol
2b, and even the product 4 of nucleophilic substitution at both
nitro groups was obtained in low yield (14%) (Scheme 2). The
major product of this reaction was disulfide 5a, i.e.,
dinitrofuroxan 1с played the role of an oxidant in this reaction.
In the current work, we continued the study of
nucleophilic nitro group substitution in 4-nitrofuroxans
1a,b by reaction with other hetarylthiols 2с–k,m, as well as
observed the behavior of 1,6-bis(4-nitrofuroxan-3-yl)
hexane (1d) and 4-nitrofuroxan-3-carboxamide (1e) in this
reaction. Nitrofuroxans 1a,b successfully reacted with thiols
2с–k,m under the previously found conditions (equimolar
177

Chemistry of Heterocyclic Compounds 2015, 51(2), 176–186
Scheme 2
ratio of reactants and DBU in MeCN at 20°С), giving the
hetarylsulfanylfuroxans 3i–ab, and the same reactivity
trend towards nucleophilic substitution was observed – the
reaction with 4-nitrofuroxan 1а occurred faster (control by
TLC) and gave higher yields of substitution products than
the reaction with nitrofuroxan 1b (Scheme 1). At the same
time, indolotriazinethiols 2c–k were found to be more
reactive compared to the dimethylpyrimidinethiol 2m. The
reaction of nitrofuroxan 1а with hetarylthiols 2с–k was
finished in 8 h with the formation of hetarylsulfanyl-
furoxans 3i–q in 70–84% yields, while the reaction with
hetarylthiol 2m required 30 h, and the yield of hetaryl-
sulfanylfuroxan 3r was merely 53%. Similar results were
obtained also in the reaction of 3-benzyl-4-nitrofuroxan
(1b) with hetarylthiols 2с–m. While the reaction of compound
1b with thiols 2c–k was accomplished in 10 h, giving the
hetarylsulfanylfuroxans 3s–z and 3aa in 61-76% yields, the
reaction with thiol 2m required stirring for 48 h, while the
hetarylsulfanylfuroxan 3ab was obtained in only 35%
yield.
The nucleophilic substitution of nitro groups in 3,3'-(hexane-
1,6-diyl)bis(4-nitrofuroxan) (1d), containing two nitro-
furoxan fragments linked by a hexamethylene chain,
predictably was even slower than the reaction of
benzylnitrofuroxan 1b (Scheme 1). Besides that, effective
substitution of both nitro groups in the starting substrate 1d
required a 20% molar excess of thiol with respect to 1 mol
of furoxan 1d. As in the previous cases, the most reactive
were derivatives of indolotriazinethiols 2a–k. The
completion of these reactions took 48 h, giving the
hetarylsulfanylfuroxans 3ac–an in up to 70% yields, while
completing the reaction with dimethylpyrimidinethiol 2m
and aminothiadiazolethiol 2n required longer time (90 and
120 h, respectively), while the yields of compounds 3ao
and 3ap were 34% and 51%, respectively.
С-3 atom of furoxan ring apparently increased the oxidizing
properties of 4-nitrofuroxans. However, the tendency to form
disulfide was observed only in the reaction of compound 1е
with indolotriazine 2d. The reaction of nitrofuroxan 1e
with pyrimidinethiols 2l,m and aminothiadiazolethiol 2n
was not successful – all experiments failed to produce nitro
group substitution products or the respective disulfides, but
thiols 2l–n were recovered unchanged from the reaction
mixtures.
In order to study the nucleophilic substitution of nitro group
in nitrofuroxans with hetaryloxy fragments, 4-nitro-
furoxans 1a–c were treated with some heterocyclic
hydroxy derivatives 6a–e.
The optimum conditions found for the reaction with
thiols (DBU/MeCN) were also effective for the reaction of
nitrofuroxans 1а–с with hydroxy heterocycles 6 (Scheme 4).
As in the case with hetarylthiols 2, 4-nitro-3-phenylfuroxan
(1a) was the most reactive nitrofuroxan in nucleophilic
substitution reactions with hydroxy heterocycles. Pyridine
derivatives 6a,b were the most reactive nucleophiles
among the hydroxy heterocycles used (reaction time 2 h),
while the quinoline derivatives 6c,d gave slower reactions
(reaction time 8 h), and the reaction with hydroxypyrazole
6e was the most difficult (48 h). The respective 4-hetaryl-
oxy-3-phenylfuroxans 7a–e were obtained in high yields
(68–90%). However, in the cases of 3-benzyl-4-nitro-
furoxan (1b) and bisnitrofuroxan 1d the reaction was no
longer universally applicable. Thus, the nitrofuroxan 1b in
reactions with hydroxy heterocycles 6a,e gave only two
types of hetarylfuroxan ethers 7f,g in 72 and 54% yields,
respectively. The reaction of furoxan 1d was successful
only with three nucleophiles 6a,d,e, giving the respective
compounds 7h–j in fair yields (61–78%), while the
reaction time increased from 4 h to 48 h in the series of
compound 6a (4 h), compound 6d (12 h), and compound
6e (48 h). The lower reactivity of hydroxy heterocycles was
apparently associated with their weaker nucleophilicity
compared to the nucleophilicity of hetarylthiols.
An interesting feature was observed during the reaction of
4-nitrofuroxan-3-carboxamide (1e) with indolotriazinethiol
2d. Instead of the expected nitro group substitution
product, we obtained the disulfide 5b. Variation of base
(Et3N versus DBU), and the reaction temperature (0–20°C)
had no effect on the direction of reaction, while the yield of
compound 5b changed insignificantly (Scheme 3), pointing
to the oxidizing properties of nitrofuroxan 1e. The presence
of electron-withdrawing substituents (NO2, CONH2) at the
The structure of the synthesized hetarylsulfanylfuroxans
3i–ap and hetaryloxyfuroxans 7a–j was confirmed by a
1
data set that consisted of elemental analysis, H and 13C
NMR spectroscopy, and high-resolution mass spectrometry.
The obtained polyheterocyclic structures had very poor
solubility even in highly polar solvents. For this reason, the
Scheme 3
N
N
H2NOC
NO2
Et3Nor DBU
N
N N
N
SH
N
MeCN
0°C or rt
56–63%
N
N
N
N
N
O
Pr
Pr
O
N
N
Pr
1e
2d
S S
5b
178

Chemistry of Heterocyclic Compounds 2015, 51(2), 176–186
Scheme 4
Experimental
reaction products were precipitated from solution with water
and carefully washed on filter with water to remove salts,
followed by washing with acetonitrile to remove possible
organic impurities. Besides that, the poor solubility of the
synthesized compounds explains the broadened shape of all 1H
NMR signals. The hetarylsulfanylfuroxans 3i–ap and
hetaryloxyfuroxans 7a–j were found to obey a general rule
applicable to all furoxans: the difference of 13C NMR
chemical shifts for the furoxan ring was ~40 ppm, that
could be explained by the increased electron density on the
ring C-3 atoms due to resonance coupling with the N-oxide
fragment.32
1H and 13C NMR spectra were acquired on a Bruker AM-300
spectrometer (300 and 75 MHz, respectively) in DMSO-d6.
The residual solvent proton signals (2.50 ppm) and 13C
signals (39.5 ppm) were used as internal standards. High-
resolution mass spectra were recorded on a Bruker
micrOTOF II instrument with electrospray ionization
(ESI). Elemental analysis was performed on Perkin–Elmer
2400 and EuroVector EA instruments. The bromine content
was determined gravimetrically. Melting points were
determined on a Sanyo Gallenkamp apparatus. The reaction
progress was controlled by TLC on Merck 60 F254 silica gel
plates (visualization under 254 nm UV light).
Thus, our study of nucleophilic nitro group substitution
in 4-nitrofuroxans with hetarylthiol and hetaryloxy
fragments allowed to identify the optimal conditions for the
formation of hetaryl thiolate anion (DBU/MeCN), which
were effective also for the formation of hetaryloxy anion,
allowing to develop a general method for the synthesis of
previously unknown heterocyclic systems containing a
furoxan ring linked to a heterocyclic fragment by S- and
О-bridges. The effects of substituents at the furoxan ring
С-3 atom and the starting hetarylthiol structure on the
reaction outcome were established. Nucleophilic substi-
tution with hetarylthiols was successful for 4-nitro-
furoxans with phenyl, benzyl, and aliphatic substituents.
With electron-withdrawing substituent (NO2, CONH2) at
this position, 4-nitrofuroxans reacted as oxidizers with
indolotriazine thiols, resulting in oxidative formation of a
disulfide bridge. In the case of less nucleophilic hydroxy
heterocycles, only 4-nitro-3-phenylfuroxan gave nucleo-
philic substitution products. Other nitrofuroxans partici-
pated in nucleophilic substitution reactions with hetero-
cyclic hydroxy compounds only in certain cases. Among
the studied hetarylthiols, indolotriazine thiols were the
most active in nucleophilic substitution reactions of
4-nitrofuroxan nitro groups, while 3-hydroxy-6-methyl-
pyridine was the most active among heterocyclic hydroxy
derivatives. The overall practical result of this study was the
preparation of a library of previously unknown hetaryl-
sulfanylfuroxans.
The starting nitrofuroxans 1а,b,d,201c,21 and 1e,22 as
well as the heterocyclic thiols 2a–g,i–m23–25 were obtained
according to published methods. 5-Amino-1,3,4-thiadiazole-
2-thiol (2n), hydroxy heterocycles 6a–d, and DBU were
commercially available (Acros). Acetonitrile was purified
by refluxing with P2O5 until the solvent no longer changed
color after adding a fresh portion of P2O5, then distilled
over anhydrous potassium carbonate.
5-(2-Phenylethyl)-5
Н-[1,2,4]triazino[5,6-b]indole-
3-thiol (2h)
.
A
suspension of 1-(2-phenylethyl)isatin33 (25.1 g,
0.100 mol) in water (400 ml) was stirred at room temperature
and treated by the addition of thiosemicarbazide (9.56 g,
0.105 mol) and K2CO3 (20.7 g, 0.150 mol). The reaction
mixture was refluxed for 4 h until complete dissolution of
the starting isatin and for additional 1 h, then filtered while
hot to remove insoluble impurities. The obtained filtrate
was cautiously acidified with 10% HCl (accompanied by
evolution of hydrogen sulfide) to pH 1, the precipitate
formed was filtered off, washed with water, and air-dried.
1
Yield 26.62 g (87%), yellow powder, mp 279–281°C. H
3
NMR spectrum, δ, ppm (J, Hz): 3.08 (2Н, t, J = 7.4,
3
NCH2CH2); 4.42 (2Н, t, J = 7.4, NCH2); 7.17–7.23 (5Н,
3
m, Н Ph); 7.34 (1H, t, J = 7.4, H Het); 7.50–7.62 (2H, m,
H Het); 7.97 (1H, d, 3J = 7.6, H Het); 14.48 (1Н, br. s, SH).
13C NMR spectrum, δ, ppm: 34.3 (NCH2CH2); 43.3
(NCH2); 112.8, 118.2, 122.7, 124.4, 127.5, 129.3, 129.8,
132.7, 136.1, 138.9, 144.4, 148.9 (C Ph, C Het); 180.1 (CS).
179

Chemistry of Heterocyclic Compounds 2015, 51(2), 176–186
Found, % C 66.60; H 4.63; N 18.27; S 10.50. C17H14N4S.
Calculated, %: C 66.64; H 4.61; N 18.29; S 10.46.
121.8, 122.0, 123.2, 127.6, 128.9, 130.9, 131.7, 141.2, 141.9,
144.8, 163.4 (C Ph, C Het); 148.9 (C-4 furoxan). Found, m/z:
419.1273 [M+H]+. C21H19N6O2S. Calculated, m/z: 419.1285.
Found, %: C 60.30; H 4.28; N 20.11; S 7.70. C21H18N6O2S.
Calculated, %: C 60.27; H 4.34; N 20.08; S 7.66.
Preparation of hetarylsulfanylfuroxans 3i–ab (General
method). DBU (0.15 ml, 1 mmol) was added at room
temperature to a stirred suspension of the respective thiol
2c–k,m (1 mmol) in anhydrous MeCN (2 ml). Furoxan 1a or
1b was added to the obtained mixture after 10 min and the
reaction mixture was stirred for 8–48 h until complete
conversion of the starting furoxan 1a or 1b (control by TLC,
eluent CHCl3). The mixture was then treated with H2O (10 ml).
The precipitate that formed was filtered off, carefully washed
with water, acetonitrile (~1 ml), and air-dried.
5-Ethyl-3-[(5-oxido-4-phenyl-1,2,5-oxadiazol-3-yl)sulfa-
nyl]-5Н-[1,2,4]triazino[5,6-b]indole (3i). Yield 319 mg
(82%), orange powder, mp 162–164°C. 1H NMR spectrum,
δ, ppm: 1.28 (3H, br. s, CH3); 4.29 (2H, br. s, CH2); 7.47
(4H, br. s, H-3,4,5 Ph, H); 7.81 (2H, br. s, H-2,6 Ph); 7.94
(2H, br. s, H); 8.32 (1H, br. s, H Het). 13C NMR spectrum,
δ, ppm: 13.1 (CH3); 36.3 (CH2); 111.6 (C-3 furoxan);
116.4, 117.0, 122.1, 123.3, 127.8, 129.0, 129.3, 131.0,
131.8, 141.0, 142.2, 145.5, 163.2 (C Ph, C Het); 149.8 (C-4
furoxan). Found, m/z: 391.0968 [M+H]+. C19H15N6O2S.
Calculated, m/z: 391.0972. Found, %: C 58.41; H 3.66;
N 21.48; S 8.23. C19H14N6O2S. Calculated, %: C 58.45; H 3.61;
N 21.53; S 8.21.
5-Benzyl-3-[(5-oxido-4-phenyl-1,2,5-oxadiazol-3-yl)sulfa-
nyl]-5Н-[1,2,4]triazino[5,6-b]indole (3m). Yield 334 mg
1
(74%), orange powder, mp 193–195°C. H NMR spectrum,
δ, ppm (J, Hz): 5.46 (2H, s, NCH2); 7.25 (5H, s, Н Ph);
7.42 (3H, br. s, H-3,4,5 3-Ph); 7.50 (2H, br. s, H-2,6, 3-Ph);
7.76 (1H, br. s, H Het); 7.88 (2H, br. s, H Het); 8.34 (1H, d,
3J = 8.4, H Het). 13C NMR spectrum, δ, ppm: 44.6 (NCH2);
111.9 (C-3 furoxan); 117.2, 122.1, 123.6, 127.6, 127.8,
128.0, 128.8, 129.0, 131.0, 131.9, 132.7, 135.5, 138.4, 141.7,
142.5, 144.7, 163.1 (C Ph, C Het); 149.1 (C-4 furoxan).
Found, m/z: 453.1119 [M+H]+. C24H17N6O2S. Calculated, m/z:
453.1128. Found, %: C 63.66; H 3.54; N 18.52; S 7.13.
C24H16N6O2S. Calculated, %: C 63.70; H 3.56; N 18.57;
S 7.09.
3-[(5-Oxido-4-phenyl-1,2,5-oxadiazol-3-yl)sulfanyl]-5-
(2-phenylethyl)-5Н-[1,2,4]triazino[5,6-b]indole (3n). Yield
326 mg (70%), bright-orange powder, mp 200–202°C.
1H NMR spectrum, δ, ppm: 2.97 (2H, br. s, NCH2CH2);
4.42 (2H, br. s, NCH2); 6.99 (2H, br. s, НPh); 7.11 (3H,
br. s, Н Ph); 7.45 (4H, br. s, H-3,4,5 3-Ph, H Het); 7.76 (2H,
br. s, H-2,6 3-Ph); 7.91 (2H, br. s, H Het); 8.27 (1H, br. s,
H Het). 13C NMR spectrum, δ, ppm: 33.4 (NCH2CH2); 42.7
(NCH2); 111.8 (C-3 furoxan); 116.3, 116.7, 121.8, 123.2,
126.5, 127.6, 128.0, 128.2, 128.5, 128.9, 130.9, 131.6,
137.6, 141.0, 141.8, 145.7, 163.2 (C Ph, C Het); 149.3 (C-4
furoxan). Found, m/z: 467.1281 [M+H]+. C25H19N6O2S.
Calculated, m/z: 467.1285. Found, %: C 64.39; H 3.86;
N 17.97; S 6.90. C25H18N6O2S. Calculated, %: C 64.36;
H 3.89; N 18.01; S 6.87.
3-[(5-Oxido-4-phenyl-1,2,5-oxadiazol-3-yl)sulfanyl]-
5-propyl-5Н-[1,2,4]triazino[5,6-b]indole (3j). Yield 339 mg
(84%), yellow powder, mp 171–173°C. 1H NMR spectrum, δ,
ppm (J, Hz): 0.78 (3H, br. s, CH3); 1.73 (2H, br. s,
CH3CH2); 4.20 (2H, br. s, NCH2); 7.48 (5H, br. s, H Ph);
7.82 (2H, br. s, H Het); 7.94 (1H, br. s, H Het); 8.33 (1H, d,
3J = 7.2, H Het). 13C NMR spectrum, δ, ppm: 11.3 (CH3);
21.1 (CH3CH2); 42.8 (NCH2); 111.7 (C-3 furoxan); 116.4,
117.0, 122.0, 122.1, 123.3, 127.7, 129.0, 131.1, 131.8, 141.5,
142.1, 146.0, 163.4 (C Ph, C Het); 149.7 (C-4 furoxan). Found,
m/z: 405.1126 [M+H]+. C20H17N6O2S. Calculated, m/z:
405.1128. Found, %: C 59.32; H 4.05; N 20.72; S 7.97.
C20H16N6O2S. Calculated, %: C 59.39; H 3.99; N 20.78; S 7.93.
5-Isopropyl-3-[(5-oxido-4-phenyl-1,2,5-oxadiazol-3-yl)-
sulfanyl]-5Н-[1,2,4]triazino[5,6-b]indole (3k). Yield 323 mg
(80%), yellow powder, mp 134–136°C. 1H NMR spectrum, δ,
5-Allyl-3-[(5-oxido-4-phenyl-1,2,5-oxadiazol-3-yl)sulfa-
nyl]-5Н-[1,2,4]triazino[5,6-b]indole (3o). Yield 293 mg
1
(73%), bright-yellow powder, mp 172–174°C. H NMR
spectrum, δ, ppm (J, Hz): 4.87 (2H, br. s, NCH2); 5.03 (1H,
3
3
d, J = 10.1, CH=CH2); 5.16 (1H, d, J = 10.1, CH=CH2);
5.88–5.93 (1H, m, CH2CH=CH2); 7.40–7.45 (5H, m,
3
3
H Ph); 7.72 (2H, t, J = 6.1, H Het); 7.88 (1H, d, J = 6.2,
3
3
ppm (J, Hz): 1.47 (6H, d, J = 6.4, CH(CH3)2); 4.95–4.99
H Het); 8.29 (1H, d, J = 7.5, H Het). 13C NMR spectrum,
(1H, m, CH(CH3)2); 7.45 (5H, br. s, H); 7.75 (1H, t,
3J = 7.6, H Het); 7.91 (2H, m, H Het); 8.30 (1H, d, 3J = 7.3,
H Het). 13C NMR spectrum, δ, ppm: 19.4, 19.7 (2CH3); 46.6
(CH(CH3)2); 112.1 (C-3 furoxan); 116.2, 117.1, 121.7, 121.9,
123.0, 127.6, 128.9, 131.0, 131.6, 140.6, 142.1, 145.4, 162.9
(C Ph, C Het); 149.7 (C-4 furoxan). Found, %: C 59.34;
H 4.03; N 20.70; S 7.96. C20H16N6O2S. Calculated, %:
C 59.39; H 3.99; N 20.78; S 7.93.
δ, ppm: 43.3 (NCH2); 111.7 (C-3 furoxan); 116.9, 117.2, 117.8,
121.9, 123.3, 127.7, 128.8, 130.8, 131.1, 131.2, 131.4, 131.7,
141.1, 142.0, 163.2 (C Ph, C Het, CH=CH2); 149.6 (C-4
furoxan). Found, m/z: 403.0947 [M+H]+. C20H15N6O2S.
Calculated, m/z: 403.0972. Found, %: C 59.73; H 3.53;
N 20.84; S 7.99. C20H14N6O2S. Calculated, %: C 59.69;
H 3.51; N 20.88; S 7.97.
5-Methyl-8-nitro-3-[(5-oxido-4-phenyl-1,2,5-oxadiazol-
5-Butyl-3-[(5-oxido-4-phenyl-1,2,5-oxadiazol-3-yl)sulfanyl]-5Н
-[1,2,4]triazino[5,6-b]indole (3l). Yield 330 mg (79%),
yellow powder, mp 178–180°C. 1H NMR spectrum, δ, ppm
(J, Hz): 0.80 (3H, br. s, CH3); 1.14 (2H, br. s, CH3CH2);
1.65 (2H, br. s, NCH2CH2); 4.19 (2H, br. s, NCH2); 7.45
(4H, br. s, H-3,4,5 Ph, H); 7.79 (2H, br. s, H-2,6 Ph); 7.91
3-yl)sulfanyl]-5Н-[1,2,4]triazino[5,6-b]indole (3p). Yield
320 mg (76%), red powder, mp 191–193°C. H NMR
1
spectrum, δ, ppm (J, Hz): 3.79 (3H, s, NCH3); 7.43–7.49
(5H, m, H Ph); 8.02 (1H, d, 3J = 8.4, H Het); 8.64 (1H, d,
3J = 8.4, H Het); 9.08 (1H, s, H Het). 13C NMR spectrum, δ,
ppm: 28.7 (NCH3); 111.6 (C-3 furoxan); 116.7, 121.8, 123.2,
126.5, 127.6, 128.2, 128.9, 130.9, 131.6, 141.0, 145.7,
163.1, 165.0 (C Ph, C Het); 149.7 (C-4 furoxan). Found,
m/z: 422.0652 [M+H]+. C18H12N7O4S. Calculated, m/z:
3
(2H, br. s, H Het); 8.30 (1H, d, J = 6.7, H Het). 13C NMR
spectrum, δ, ppm: 13.2 (CH3); 19.4 (CH3CH2); 29.5
(NCH2CH2); 42.3 (NCH2); 111.5 (C-3 furoxan); 116.1, 116.9,
180

Chemistry of Heterocyclic Compounds 2015, 51(2), 176–186
422.0666. Found, %: C 51.26; H 2.68; N 23.25; S 7.63.
ppm (J, Hz): 1.24 (6H, d, 3J = 6.6, CH(CH3)2); 4.26 (2H, s,
C18H11N7O4S. Calculated, %: C 51.30; H 2.63; N 23.27;
S 7.61.
CH2Ph); 4.81–4.89 (1H, m, CH(CH3)2); 7.29 (5H, s, H Ph);
3
7.50 (1H, d, J = 7.1, H Het); 7.72–7.78 (2H, m, H Het);
3
8-Bromo-5-methyl-3-[(5-oxido-4-phenyl-1,2,5-oxadi-
azol-3-yl)sulfanyl]-5Н-[1,2,4]triazino[5,6-b]indole (3q). Yield
8.38 (1H, d, J = 7.2, H Het). 13C NMR spectrum, δ, ppm:
18.5, 18.9 (2CH3); 29.6 (CH2Ph); 47.2 (CH(CH3)2); 111.7 (C-3
furoxan); 116.0, 117.6, 121.2, 121.7, 123.6, 127.3, 129.4,
131.5, 131.9, 141.2, 142.4, 145.7, 163.6 (C Ph, C Het);
149.9 (C-4 furoxan). Found, m/z: 419.1271 [M+H]+.
C21H19N6O2S. Calculated, m/z: 419.1285. Found, %:
C 60.26; H 4.37; N 20.05; S 7.65. C21H18N6O2S.
Calculated, %: C 60.27; H 4.34; N 20.08; S 7.66.
3-[(4-Benzyl-5-oxido-1,2,5-oxadiazol-3-yl)sulfanyl]-5-
butyl-5Н-[1,2,4]triazino[5,6-b]indole (3v). Yield 263 mg
(61%), dark-yellow powder, mp 194–196°C. 1H NMR
spectrum, δ, ppm: 0.66 (3H, br. s, CH3); 1.23 (2H, br. s,
CH3CH2); 1.72 (2H, br. s, NCH2CH2); 4.14 (2H, br. s,
NCH2); 4.33 (2H, s, CH2Ph); 7.38 (5H, s, H Ph); 7.56 (1H,
br. s, H Het); 7.79 (2H, br. s, H Het); 8.42 (1H, br. s,
H Het). 13C NMR spectrum, δ, ppm: 13.7 (CH3); 19.8
CH3CH2); 28.9, 29.8 (CH2Ph, NCH2CH2); 42.1 (NCH2);
110.1 (C-3 furoxan); 115.3, 116.7, 121.1, 122.6, 123.9,
127.8, 129.3, 130.7, 131.8, 141.0, 141.6, 145.3, 163.8
(C Ph, C Het); 149.6 (C-4 furoxan). Found, m/z: 433.1429
[M+H]+. C22H21N6O2S. Calculated, m/z: 433.1441. Found,
%: C 61.07; H 4.71; N 19.41; S 7.44. C22H20N6O2S.
Calculated, %: C 61.10; H 4.66; N 19.43; S 7.41.
1
359 mg (79%), orange powder, mp 198–200°C. H NMR
spectrum, δ, ppm: 3.68 (3H, s, NCH3); 7.43 (3H, br. s, H-3,4,5
Ph); 7.73 (2H, br. s, H-2,6 Ph); 7.89 (2H, br. s, H Het); 8.40
(1H, br. s, H Het). 13C NMR spectrum, δ, ppm: 28.2 (NCH3);
109.2 (C-3 furoxan); 114.0, 115.8, 119.3, 122.4, 124.5, 128.3,
129.4, 131.4, 134.5, 141.4, 141.8, 146.6, 164.2 (C Ph, C Het);
150.1 (C-4 furoxan). Found, m/z: 456.9904 [M(81Br)+H]+,
454.9923 [M(79Br)+H]+. C18H12BrN6O2S. Calculated, m/z:
456.9900, 454.9920. Found, %: C 47.44; H 2.46; Br 17.50;
N 18.43; S 7.03. C18H11BrN6O2S. Calculated, %: C 47.48;
H 2.44; Br 17.55; N 18.46; S 7.04.
4,6-Dimethyl-2-[(5-oxido-4-phenyl-1,2,5-oxadiazol-3-yl)
sulfanyl]pyrimidine (3r). Yield 159 mg (53%), yellow
1
powder, mp 161–163°C. H NMR spectrum, δ, ppm: 2.21
(6H, s, 2CH3); 6.99 (1H, s, H Het); 7.47 (3H, br. s, H-3,4,5
Ph); 7.72 (2H, br. s, H-2,6 Ph). 13C NMR spectrum, δ, ppm:
23.1, 23.3 (2CH3), 111.8 (C-3 furoxan); 117.6, 117.8,
122.3, 127.5, 128.7, 130.7, 167.8 (C Ph, C Het); 151.6 (C-4
furoxan). Found, m/z: 301.0728 [M+H]+. C14H13N4O2S.
Calculated, m/z: 301.0754. Found, %: C 56.03; H 3.98;
N 18.62; S 10.72. C14H12N4O2S. Calculated, %: C 55.99;
H 4.03; N 18.65; S 10.68.
3-[(4-Benzyl-5-oxido-1,2,5-oxadiazol-3-yl)sulfanyl]-
5-ethyl-5Н-[1,2,4]triazino[5,6-b]indole (3s). Yield 303 mg
(75%), yellow powder, mp 229–231°C. 1H NMR spectrum, δ,
ppm: 1.32 (3H, br. s, CH2CH3); 4.16 (2H, br. s, CH2Ph);
4.36 (2H, br. s, CH2CH3); 7.32 (5H, s, H Ph); 7.50–7.56 (1H,
m, H Het); 7.79–7.86 (2H, m, H Het); 8.33–8.37 (1H, m,
H Het). 13C NMR spectrum, δ, ppm: 12.4 (CH3); 28.9
(CH2Ph); 37.7 (NCH2); 110.2 (C-3 furoxan); 116.3, 116.9,
122.4, 124.5, 127.9, 129.2, 129.8, 131.3, 132.1, 141.4,
142.1, 144.8, 162.7 (C Ph, C Het); 149.9 (C-4 furoxan).
Found, m/z: 405.1106 [M+H]+. C20H17N6O2S. Calculated, m/z:
405.1128. Found, %: C 59.37; H 4.01; N 20.83; S 7.90.
C20H16N6O2S. Calculated, %: C 59.39; H 3.99; N 20.78;
S 7.93.
5-Benzyl-3-[(4-benzyl-5-oxido-1,2,5-oxadiazol-3-yl)-
sulfanyl]-5Н-[1,2,4]triazino[5,6-b]indole (3w). Yield 303 mg
(65%), orange powder, mp 241–243°C. 1H NMR spectrum,
δ, ppm (J, Hz): 4.21 (2H, s, CH2Ph); 5.35 (2H, br. s,
NCH2); 6.69 (3H, br. s, NCH2C6H5); 6.92 (2H, br. s,
3
NCH2C6H5); 7.34 (5H, s, H Ph); 7.52 (1H, d, J = 7.6,
3
H Het); 7.71–7.75 (2H, m, H Het); 8.38 (1H, d, J = 7.6,
H Het). 13C NMR spectrum, δ, ppm: 29.1 (CH2Ph); 44.4
(NCH2); 111.4 (C-3 furoxan); 116.6, 122.4, 123.2, 127.2,
127.4, 127.9, 128.6, 129.1, 131.4, 131.8, 132.6, 135.3, 137.9,
140.4, 141.8, 145.2, 163.6 (C Het); 149.7 (C-4 furoxan). Found,
m/z: 467.1267 [M+H]+. C25H19N6O2S. Calculated, m/z:
467.1285. Found, %: C 64.34; H 3.88; N 18.05; S 6.86.
C25H18N6O2S. Calculated, %: C 64.36; H 3.89; N 18.01;
S 6.87.
3-[(4-Benzyl-5-oxido-1,2,5-oxadiazol-3-yl)sulfanyl]-
5-propyl-5Н-[1,2,4]triazino[5,6-b]indole (3t). Yield 318 mg
(76%), dark-yellow powder, mp 239–241°C. 1H NMR
spectrum, δ, ppm (J, Hz): 0.32 (3H, t, 3J = 7.1, CH3); 1.34–
3-[(4-Benzyl-5-oxido-1,2,5-oxadiazol-3-yl)sulfanyl]-5-
(2-phenylethyl)-5Н-[1,2,4]triazino[5,6-b]indole (3x). Yield
326 mg (68%), orange powder, mp 174–176°C. H NMR
1
spectrum, δ, ppm (J, Hz): 2.88 (2H, br. s, NCH2CH2); 4.18
(2H, s, CH2Ph); 4.45 (2H, br. s, NCH2); 6.85 (3H, br. s,
(CH2)2C6H5); 6.97 (2H, br. s, (CH2)2C6H5); 7.29 (5H, s,
CH2C6H5); 7.46 (1H, br. s, H Het); 7.74 (2H, br. s, H Het);
3
1.41 (2H, m, CH3CH2); 4.14 (2H, t, J = 6.2, NCH2); 4.39
3
(2H, s, CH2Ph); 7.37 (5H, s, H Ph); 7.50 (1H, t, J = 5.9,
3
H Het); 7.71–7.77 (2H, m, H Het); 8.37 (1H, d, J = 7.7,
H Het). 13C NMR spectrum, δ, ppm: 10.5 (CH3); 20.7
(CH3CH2); 29.1 (CH2Ph); 42.6 (NCH2); 111.4 (C-3
furoxan); 116.9, 121.8, 123.1, 124.6, 128.1, 128.7, 129.3,
131.4, 132.9, 141.1, 141.6, 146.5, 164.1 (C Ph, C Het);
149.9 (C-4 furoxan). Found, m/z: 419.1264 [M+H]+.
C21H19N6O2S. Calculated, m/z: 419.1285. Found, %: C 60.23;
H 4.32; N 20.06; S 7.69. C21H18N6O2S. Calculated, %:
C 60.27; H 4.34; N 20.08; S 7.66.
8.33 (1H, d, J = 7.2, H Het). 13C NMR spectrum, δ, ppm:
3
29.0 (CH2Ph); 33.3 (NCH2CH2); 42.6 (NCH2); 111.5 (C-3
furoxan); 116.9, 121.8, 123.0, 126.3, 128.0, 128.2, 128.3,
128.4, 129.1, 129.6, 129.9, 131.4, 137.4, 141.0, 141.8, 146.4,
164.3 (C Het); 149.4 (C-4 furoxan). Found, m/z: 481.1426
[M+H]+. C26H21N6O2S. Calculated, m/z: 481.1441. Found,
%: C 65.01; H 4.18; N 17.50; S 6.65. C26H20N6O2S.
Calculated, %: C 64.98; H 4.20; N 17.49; S 6.67.
3-[(4-Benzyl-5-oxido-1,2,5-oxadiazol-3-yl)sulfanyl]-
5-isopropyl-5Н-[1,2,4]triazino[5,6-b]indole (3u). Yield 301 mg
(72%), yellow powder, mp 163–165°C. 1H NMR spectrum, δ,
5-Allyl-3-[(4-benzyl-5-oxido-1,2,5-oxadiazol-3-yl)sulfa-
nyl]-5Н-[1,2,4]triazino[5,6-b]indole (3y). Yield 245 mg
(59%), bright-yellow powder, mp 188–190°C. H NMR
1
181

Chemistry of Heterocyclic Compounds 2015, 51(2), 176–186
spectrum, δ, ppm (J, Hz): 4.23 (2H, s, CH2Ph); 4.82 (2H,
precipitate formed was filtered off, carefully washed with
water, 0.75 N NaOH, then again with water, acetonitrile
(~1 ml), and air-dried.
3
br. s, NCH2); 5.05 (1H, d, J = 10.3, CH=CH2); 5.19 (1H,
3
d, J = 10.3, CH=CH2); 5.62–5.68 (1H, m, CH2CH=CH2);
7.33 (5H, s, H Ph); 7.51 (2H, t, 3J=7.6, H Het); 7.74 (1H, d,
3,3'-{(Hexane-1,6-diyl)bis[(5-oxido-1,2,5-oxadiazole-
4,3-diyl)sulfanediyl]}bis(5Н-[1,2,4]triazino-[5,6-b]indole)
(3ac). Yield 412 mg (63%), orange powder, mp 239–241°C.
1H NMR spectrum, δ, ppm: 1.19 (4H, br. s, (CH2)2(CH2)2(CH2)2);
1.58 (4H, br. s, CH2CH2(CH2)2CH2CH2); 3.57 (4H, br. s,
CH2(CH2)4CH2); 7.56 (2H, br. s, H Het); 7.82 (4H, br. s,
H Het); 8.34 (2H, br. s, H Het); 12.94 (2H, br. s, 2NH).
13C NMR spectrum, δ, ppm: 21.4 ((CH2)2(CH2)2(CH2)2);
23.6 (CH2CH2(CH2)2CH2CH2); 27.9 (CH2(CH2)4CH2);
111.2 (C-3 furoxan); 121.3, 122.5, 122.9, 126.8, 133.9,
140.7, 142.4, 145.5, 163.8 (C Het); 151.2 (C-4 furoxan).
Found, m/z: 655.1388 [M+H]+. C28H23N12O4S2. Calculated,
m/z: 655.1401. Found, %: C 51.45; H 3.43; N 25.60;
S 9.84. C28H22N12O4S2. Calculated, %: C 51.37; H 3.39;
N 25.67; S 9.80.
3
3J = 7.7, H Het); 8.39 (1H, d, J = 7.9, H Het). 13C NMR
spectrum, δ, ppm: 28.9 (CH2Ph); 43.6 (NCH2); 110.9 (C-3
furoxan); 116.7, 117.3, 117.9, 122.9, 123.8, 127.8, 128.4,
130.2, 131.0, 131.3, 131.5, 131.9, 141.4, 142.6 163.0
(C Het, CH=CH2); 149.8 (C-4 furoxan). Found, m/z:
417.1114 [M+H]+. C21H17N6O2S. Calculated, m/z: 417.1128.
Found, %: C 60.59; H 3.85; N 20.14; S 7.72. C21H16N6O2S.
Calculated, %: C 60.56; H 3.87; N 20.18; S 7.70.
3-[(4-Benzyl-5-oxido-1,2,5-oxadiazol-3-yl)sulfanyl]-
5-methyl-8-nitro-5Н-[1,2,4]triazino[5,6-b]indole (3z). Yield
1
283 mg (65%), red powder, mp 196–198°C. H NMR
spectrum, δ, ppm (J, Hz): 3.84 (3H, s, NCH3); 4.18 (2H, s,
3
CH2Ph); 7.31 (5H, s, H Ph); 7.92 (1H, d, J = 8.1, H Het);
3
8.56 (1H, d, J = 8.1, H Het); 8.94 (1H, s, H Het).
13C NMR spectrum, δ, ppm: 28.1 (NCH3); 29.7 (CH2Ph);
111.3 (C-3 furoxan); 115.9, 121.4, 123.1, 126.8, 127.7,
128.5, 129.3, 130.7, 131.8, 140.3, 145.2, 163.5 (C Het);
149.8 (C 4 furoxan); 165.8 (CNO2). Found, m/z: 436.0807
[M+H]+. C19H14N7O4S. Calculated, m/z: 436.0823. Found,
%: C 52.43; H 2.98; N 22.48; S 7.37. C19H13N7O4S.
Calculated, %: C 52.41; H 3.01; N 22.52; S 7.36.
3-[(4-Benzyl-5-oxido-1,2,5-oxadiazol-3-yl)sulfanyl]-
8-bromo-5-methyl-5Н-[1,2,4]triazino[5,6-b]indole (3aa).
Yield 338 mg (72%), dark-yellow powder, mp 204–206°C.
1H NMR spectrum, δ, ppm (J, Hz): 3.66 (3H, s, NCH3);
4.19 (2H, s, CH2Ph); 7.29 (5H, s, H Ph); 7.64 (1H, d,
3J = 8.6, H Het); 7.88 (1H, d, 3J = 8.6, H Het); 8.22 (1H, br.
s, H Het). 13C NMR spectrum, δ, ppm: 28.2 (NCH3); 29.3
(CH2Ph); 110.3 (C-3 furoxan); 114.2, 116.7, 119.9, 122.1, 125.7,
128.7, 129.3, 131.0, 134.7, 141.2, 141.8, 145.8, 163.7 (C Het);
149.7 (C-4 furoxan). Found, m/z: 471.0052 [M(81Br)+H]+,
469.0071 [M(79Br)+H]+. C19H14BrN6O2S. Calculated, m/z:
471.0056, 469.0077. Found, %: C 48.59; H 2.83; Br 16.99;
N 17.87; S 6.85. C19H13BrN6O2S. Calculated, %: C 8.62;
H 2.79; Br 17.03; N 17.91; S 6.83.
3,3'-{(Hexane-1,6-diyl)bis[(5-oxido-1,2,5-oxadiazole-
4,3-diyl)sulfanediyl]}bis(5-methyl-5Н-[1,2,4]triazino[5,6-b]-
indole) (3ad). Yield 375 mg (55%), orange powder, mp
187–189°C. 1H NMR spectrum, δ, ppm (J, Hz): 1.23 (4H, br. s,
(CH2)2(CH2)2(CH2)2); 1.53 (4H, br. s, CH2CH2(CH2)2CH2CH2);
3.75 (10H, br. s, CH2(CH2)4CH2, 2NCH3); 7.51 (2H, d, 3J = 7.6,
H Het); 7.79 (4H, br. s, H Het); 8.30 (2H, d, 3J = 7.6, H Het).
13C NMR spectrum, δ, ppm: 22.0 ((CH2)2(CH2)2(CH2)2);
23.8 (CH2CH2(CH2)2CH2CH2); 27.5 (CH2(CH2)4CH2); 28.2
(NCH3), 109.4 (C-3 furoxan); 121.8, 122.4, 123.3, 125.6,
131.7, 140.3, 141.6, 144.7, 163.6 (C Het); 152.4 (C-4
furoxan). Found, m/z: 683.1697 [M+H]+. C30H27N12O4S2.
Calculated, m/z: 683.1714. Found, %: C 52.81; H 3.79;
N 24.60; S 9.44. C30H26N12O4S2. Calculated, %: C 52.78;
H 3.84; N 24.62; S 9.39.
3,3'-{(Hexane-1,6-diyl)bis[(5-oxido-1,2,5-oxadiazole-
4,3-diyl)sulfanediyl]}bis(5-ethyl-5Н-[1,2,4]triazino[5,6-b]-
indole) (3ae). Yield 483 mg (68%), yellow powder, mp
196–198°C. 1H NMR spectrum, δ, ppm: 1.21–1.28 (10H, m,
(CH2)2(CH2)2(CH2)2, 2CH3); 1.55 (4H, br. s, CH2CH2(CH2)2CH2CH2);
3.54 (4H, br. s, CH2(CH2)4CH2); 4.27–4.32 (4H, m, 2NCH2);
7.55–7.59 (2H, m, H Het); 7.79–7.85 (4H, m, H Het); 8.33–
8.36 (2H, m, H Het). 13C NMR spectrum, δ, ppm: 13.6
(CH3); 21.7 ((CH2)2(CH2)2(CH2)2); 23.9 (CH2CH2(CH2)2CH2CH2);
28.6 (CH2(CH2)4CH2); 36.9 (2CH2); 111.6 (C-3 furoxan);
121.1, 122.6, 123.7, 125.2, 130.3, 140.7, 141.9, 144.2, 163.8
(C Het); 150.1 (C-4 furoxan). Found, m/z: 711.2027 [M+H]+.
C32H31N12O4S2. Calculated, m/z: 711.2027. Found, %: C 54.01;
H 4.29; N 23.61; S 8.98. C32H30N12O4S2. Calculated, %:
C 54.07; H 4.25; N 23.65; S 9.02.
4,6-Dimethyl-2-[(4-benzyl-5-oxido-1,2,5-oxadiazol-3-yl)-
sulfanyl]pyrimidine (3ab). Yield 110 mg (35%), yellow
1
powder, mp 169–171°C. H NMR spectrum, δ, ppm (J,
Hz): 2.14 (6H, s, 2CH3); 4.24 (2H, s, CH2Ph); 6.87 (1H, s,
H Het); 7.36 (5H, s, H Ph). 13C NMR spectrum, δ, ppm:
22.4, 22.5 (2CH3); 28.8 (CH2Ph); 111.3 (C-3 furoxan);
115.2, 117.4, 122.8, 126.9, 128.4, 129.9, 166.3 (C Ph,
C Het); 150.2 (C-4 furoxan). Found, m/z: 315.0894 [M+H]+.
C15H15N4O2S. Calculated, m/z: 315.0910. Found, %: C 57.28;
H 4.50; N 17.79; S 10.24. C15H14N4O2S. Calculated, %:
C 57.31; H 4.49; N 17.82; S 10.20.
Preparation of compounds 3ac–ap (General method).
DBU (0.33 ml, 2.2 mmol) was added dropwise at room
temperature to a stirred suspension of the respective thiol
2a–n (2.2 mmol) in anhydrous MeCN (4 ml). The obtained
mixture was stirred for 15 min and then furoxan 1d (0.34 g,
1.0 mmol) was added. The reaction mixture was further
stirred for 48–120 h until complete conversion of the
starting furoxan 1d (control by TLC, eluent CHCl3). The
reaction mixture was then diluted with H2O (20 ml). The
3,3'-{(Hexane-1,6-diyl)bis[(5-oxido-1,2,5-oxadiazole-
4,3-diyl)sulfanediyl]}bis(5-propyl-5Н-[1,2,4]triazino[5,6-b]-
indole) (3af). Yield 480 mg (65%), light-yellow powder,
1
mp 210–212°C. H NMR spectrum, δ, ppm (J, Hz): 0.68
(6H, br. s, 2CH3); 1.14 (4H, br. s, (CH2)2(CH2)2(CH2)2);
1.50 (4H, br. s, CH2CH2(CH2)2CH2CH2); 1.65 (4H, br. s,
2CH3CH2); 3.51 (4H, br. s, CH2(CH2)4CH2); 4.33 (4H,
br. s, 2NCH2); 7.81 (4H, br. s, H Het); 7.94 (2H, br. s,
3
H Het); 8.33 (2H, d, J = 7.1, H Het). 13C NMR spectrum,
δ, ppm: 11.2 (CH3); 20.4 (CH3CH2); 22.1 ((CH2)2(CH2)2(CH2)2);
23.4 (CH2CH2(CH2)2CH2CH2); 29.7 (CH2(CH2)4CH2); 43.4
182

Chemistry of Heterocyclic Compounds 2015, 51(2), 176–186
H Het); 7.73 (4H, br. s, H Het); 8.36 (2H, br. s, H Het).
(NCH2); 110.4 (C-3 furoxan); 116.4, 122.0, 122.5, 123.7,
131.6, 141.1, 141.9, 146.6, 163.9 (C Het); 149.9 (C-4
furoxan). Found, m/z: 739.2329 [M+H]+. C34H35N12O4S2.
Calculated, m/z: 739.2340. Found, %: C 55.32; H 4.59;
N 22.72; S 8.70. C34H34N12O4S2. Calculated, %: C 55.27;
H 4.64; N 22.75; S 8.68.
3,3'-{(Hexane-1,6-diyl)bis[(5-oxido-1,2,5-oxadiazole-
4,3-diyl)sulfanediyl]}bis(5-isopropyl-5Н-[1,2,4]triazino[5,6-b]-
indole) (3ag). Yield 421 mg (57%), light-yellow powder,
mp 158–160°C. 1H NMR spectrum, δ, ppm: 1.23 (4H, br. s,
(CH2)2(CH2)2(CH2)2); 1.45 (16H, br. s, CH2CH2(CH2)2CH2CH2,
2CH3); 3.56 (4H, br. s, CH2(CH2)4CH2); 4.74–4.80 (2H, m,
2CH(CH3)2); 7.48 (2H, br. s, H Het); 7.71 (4H, br. s, H Het); 8.34
(2H, br. s, H Het). 13C NMR spectrum, δ, ppm: 19.3, 19.7 (CH3);
21.8 ((CH2)2(CH2)2(CH2)2); 24.0 (CH2CH2(CH2)2CH2CH2);
27.5 (CH2(CH2)4CH2); 46.5 (CH(CH3)2); 111.7 (C-3
furoxan); 112.1, 117.0, 121.8, 122.9, 131.3, 140.6, 141.7,
146.0, 163.4 (C Het); 149.3 (C-4 furoxan). Found, %:
C 55.25; H 4.68; N 22.73; S 8.74. C34H34N12O4S2.
Calculated, %: C 55.27; H 4.64; N 22.75; S 8.68.
13C NMR spectrum, δ, ppm: 21.9 ((CH2)2(CH2)2(CH2)2); 24.6
(CH2CH2(CH2)2CH2CH2); 28.3 (CH2(CH2)4CH2); 32.1
(NCH2CH2); 44.2 (NCH2); 111.6 (C-3 furoxan); 117.2,
122.0, 123.3, 127.1, 127.8, 128.0, 128.7, 131.5, 135.2,
140.9, 141.8, 146.4, 164.4 (C Het); 149.5 (C-4 furoxan).
Found, %: C 61.20; H 4.51; N 19.45; S 7.46. C44H38N12O4S2.
Calculated, %: C 61.24; H 4.44; N 19.48; S 7.43.
3,3'-{(Hexane-1,6-diyl)bis[(5-oxido-1,2,5-oxadiazole-
4,3-diyl)sulfanediyl]}bis(5-allyl-5Н-[1,2,4]triazino[5,6-b]-
indole) (3ak). Yield 308 mg (42%), bright-yellow powder,
mp 174–176°C. 1H NMR spectrum, δ, ppm (J, Hz): 1.19 (4H, br. s,
(CH2)2(CH2)2(CH2)2); 1.62 (4H, br. s, CH2CH2(CH2)2CH2CH2);
3.71 (4H, br. s, CH2(CH2)4CH2); 4.82 (4H, br. s, NCH2);
3
3
5.04 (2H, d, J = 10.2, CH=CH2); 5.19 (2H, d, J = 10.2,
CH=CH2); 5.66–5.72 (2H, m, CH2CH=CH2); 7.48–7.52 (4H,
m, H Het); 7.69–7.75 (2H, m, H Het); 8.40 (2H, d, 3J = 6.7,
H Het). 13C NMR spectrum, δ, ppm: 21.6 ((CH2)2(CH2)2(CH2)2);
23.7 (CH2CH2(CH2)2CH2CH2); 29.1 (CH2(CH2)4CH2); 43.5
(NCH2); 109.4 (C-3 furoxan); 116.7, 117.4, 118.6, 121.7,
123.6, 127.1, 131.3, 131.8, 141.7, 142.6, and 163.6 (C Het,
CH=CH2); 149.8 (C-4 furoxan). Found, m/z: 735.2013
[M+H]+. C34H31N12O4S2. Calculated, m/z: 735.2027.
3,3'-{(Hexane-1,6-diyl)bis[(5-oxido-1,2,5-oxadiazole-
4,3-diyl)sulfanediyl]}bis(5-butyl-5Н-[1,2,4]triazino[5,6-b]-
indole) (3ah). Yield 536 mg (70%), yellow powder, mp
1
Found, %:
C 55.54; H 4.17; N 22.93; S 8.69.
197–199°C. H NMR spectrum, δ, ppm (J, Hz): 0.86 (6H,
C34H30N12O4S2. Calculated, %: C 55.57; H 4.12; N 22.87;
S 8.73.
br. s, 2CH3); 1.17 (8H, br. s, (CH2)2(CH2)2(CH2)2, 2CH3CH2);
1.61 (8H, br. s, CH2CH2(CH2)2CH2CH2, 2NCH2CH2); 3.68
(4H, br. s, CH2(CH2)4CH2); 4.14 (4H, br. s, 2NCH2); 7.49
(2H, br. s, H Het); 7.87 (4H, br. s, H Het); 8.26 (2H, d, 3J = 6.9,
H Het). 13C NMR spectrum, δ, ppm: 13.7 (CH3); 19.8 (CH3CH2);
22.4 ((CH2)2(CH2)2(CH2)2); 24.7 (CH2CH2(CH2)2CH2CH2); 29.8
(CH2(CH2)4CH2); 31.4 (NCH2CH2); 43.8 (NCH2); 110.3 (C-3
furoxan); 116.1, 116.9, 121.8, 123.2, 131.7, 141.2, 141.9,
144.8, 163.7 (C Het); 149.7 (C-4 furoxan). Found, m/z:
767.2639 [M+H]+. C36H39N1-2O4S2. Calculated, m/z: 767.2653.
Found, %: C 56.43; H 5.02; N 21.88; S 8.39. C36H38N12O4S2.
Calculated, %: C 56.38; H 4.99; N 21.92; S 8.36.
3,3'-{(Hexane-1,6-diyl)bis[(5-oxido-1,2,5-oxadiazole-
4,3-diyl)sulfanediyl]}bis(5-benzyl-5Н-[1,2,4]triazino[5,6-b]-
indole) (3ai). Yield 450 mg (54%), orange powder, mp 206–
208°C. 1H NMR spectrum, δ, ppm (J, Hz): 1.18 (4H, br. s,
(CH2)2(CH2)2(CH2)2); 1.52 (4H, br. s, CH2CH2(CH2)2CH2CH2);
3.64 (4H, br. s, CH2(CH2)4CH2); 5.32 (4H, s, 2NCH2Ph);
7.29 (10H, s, 2NCH2C6H5); 7.73 (2H, br. s, H Het); 7.94 (4H,
br. s, H Het); 8.32 (2H, d, 3J = 8.2, H Het). 13C NMR spectrum, δ,
ppm: 20.3 ((CH2)2(CH2)2(CH2)2); 24.6 (CH2CH2(CH2)2CH2CH2);
29.1 (CH2(CH2)4CH2); 44.9 (NCH2); 110.2 (C-3 furoxan);
116.1, 117.2, 122.1, 123.6, 128.0, 128.8, 129.0, 131.9,
132.7, 141.7, 142.5, 144.7, 163.7 (C Het); 149.9 (C-4 furoxan).
Found, m/z: 835.2322 [M+H]+. C42H35N12O4S2. Calculated, m/z:
835.2340. Found, %: C 60.38; H 4.07; N 20.09; S 7.73.
C42H34N12O4S2. Calculated, %: C 60.42; H 4.10; N 20.13; S 7.68.
3,3'-{(Hexane-1,6-diyl)bis[(5-oxido-1,2,5-oxadiazole-
3,3'-{(Hexane-1,6-diyl)bis[(5-oxido-1,2,5-oxadiazole-
4,3-diyl)sulfanediyl]}bis(5-methyl-8-nitro-5Н-[1,2,4]triazino-
[5,6-b]indole) (3al). Yield 486 mg (63%), orange powder, mp
132–134°C. 1H NMR spectrum, δ, ppm (J, Hz): 1.22 (4H, br. s,
(CH2)2(CH2)2(CH2)2); 1.58 (4H, br. s, CH2CH2(CH2)2CH2CH2);
3.63 (4H, br. s, CH2(CH2)4CH2); 3.86 (6H, s, 2NCH3); 8.07 (2H,
d, 3J = 8.0, H Het); 8.56 (2H, d, 3J = 8.0, H Het); 9.01 (2H, s,
H Het). 13C NMR spectrum, δ, ppm: 21.2 ((CH2)2(CH2)2(CH2)2);
23.9 (CH2CH2(CH2)2CH2CH2); 28.3 (NCH3); 29.7
(CH(CH2)4CH2); 109.3 (C-3 furoxan); 116.7, 121.8, 126.5,
127.6, 131.6, 141.0, 145.7, 163.4 (C Het); 149.9 (C-4
furoxan); 165.7 (CNO2). Found, m/z: 773.1402 [M+H]+.
C30H25N14O8S2. Calculated, m/z: 773.1416. Found, %:
C 46.60; H 3.17; N 25.32; S 8.34. C30H24N14O8S2. Calculated, %:
C 46.63; H 3.13; N 25.38; S 8.30.
3,3'-{(Hexane-1,6-diyl)bis[(5-oxido-1,2,5-oxadiazole-
4,3-diyl)sulfanediyl]}bis(8-bromo-5-methyl-5Н-[1,2,4]tri-
azino[5,6-b]indole) (3am). Yield 420 mg (50%), dark-
1
yellow powder, mp 183–185°C. H NMR spectrum, δ, ppm:
1.19 (4H, br. s, (CH2)2(CH2)2(CH2)2); 1.53 (4H, br. s,
CH2CH2(CH2)2CH2CH2); 3.55 (4H, br. s, CH2(CH2)4CH2);
3.78 (6H, s, 2NCH3); 7.97 (4H, br. s, H Het); 8.43 (2H, br. s,
H Het). 13C NMR spectrum, δ, ppm: 21.1 ((CH2)2(CH2)2(CH2)2);
24.6(CH2CH2(CH2)2CH2CH2); 28.6 (NCH3); 29.1 (CH2(CH2)4CH2);
109.8 (C-3 furoxan); 114.3, 115.9, 118.4, 124.8, 133.8,
141.1, 141.7, 145.4, 164.0 (C Het); 149.7 (C-4 furoxan).
Found, %: C 42.91; H 2.93; Br 18.98; N 19.96; S 7.60.
C30H24Br2N12O4S2. Calculated, %: C 42.87; H 2.88; Br 19.01;
N 20.00; S 7.63.
4,3-diyl)sulfanediyl]}bis(5-(2-phenylethyl)-5Н-[1,2,4]tri-
azino[5,6-b]indole) (3aj). Yield 414 mg (48%), orange
1
powder, mp 213–215°C. H NMR spectrum, δ, ppm: 1.13
2,2'-{(Hexane-1,6-diyl)bis[(5-oxido-1,2,5-oxadiazole-
4,3-diyl)sulfanediyl]}bis(4,6-diaminopyrimidine) (3an).
Yield 299 mg (56%), yellow powder, mp 177–179°C. 1H NMR
spectrum, δ, ppm: 1.27 (4H, br. s, (CH2)2(CH2)2(CH2)2); 1.60
(4H, br. s, (CH2)2(CH2)2(CH2)2); 1.58 (4H, br. s, CH2CH2
(CH2)2CH2CH2); 2.33 (4H, br. s, 2NCH2CH2); 3.73 (4H,
br. s, CH2(CH2)4CH2); 4.22 (4H, br. s, 2NCH2); 6.71 (6H,
br. s, 2CH2C6H5); 6.92 (4H, br. s, 2CH2C6H5); 7.47 (2H, br. s,
183

Chemistry of Heterocyclic Compounds 2015, 51(2), 176–186
(4H, br. s, CH2CH2(CH2)2CH2CH2); 3.47 (4H, br. s, CH2(CH2)4CH2);
the addition of furoxan 1a or 1b (1 mmol) or furoxan 1d
(0.5 mmol) and stirred for 2–48 h until complete
conversion of the starting furoxan (control by TLC, eluent
CHCl3). The reaction mixture was then diluted with H2O
(10 ml). The precipitate formed was filtered off, carefully
washed with water, and air-dried.
5.19 (2H, s, H Het); 6.21 (8H, s, 4NH2). 13C NMR
spectrum, δ, ppm: 18.9 ((CH2)2(CH2)2(CH2)2); 24.9
(CH2CH2(CH2)2CH2CH2); 29.3 (CH2(CH2)4CH2); 79.8 (CH
Het); 111.3 (C-3 furoxan); 151.9 (C-4 furoxan); 163.7
(CNH2); 166.9 (CS). Found, m/z: 535.1378 [M+H]+.
C18H23N12O4S2. Calculated, m/z: 535.1401. Found, %:
C 40.40; H 4.19; N 31.38; S 11.97. C18H22N12O4S2.
Calculated, %: C 40.44; H 4.15; N 31.44; S 12.00.
2-Methyl-5-[(5-oxido-4-phenyl-1,2,5-oxadiazol-3-yl)-
oxy]pyridine (7a). Yield 242 mg (90%), white powder, mp
102–104°C. 1H NMR spectrum, δ, ppm (J, Hz): 2.53 (3Н, s,
3
2,2'-{(Hexane-1,6-diyl)bis[(5-oxido-1,2,5-oxadiazole-
4,3-diyl)sulfanediyl]}bis(4,6-dimethylpyrimidine) (3ao).
Yield 180 mg (34%), bright-yellow powder, mp 182–184°C.
1H NMR spectrum, δ, ppm: 1.22 (4H, br. s, (CH2)2(CH2)2(CH2)2);
1.54 (4H, br. s, CH2CH2(CH2)2CH2CH2); 2.21 (12H, s,
4CH3); 3.54 (4H, br. s, CH2(CH2)4CH2); 6.99 (2H, s, 2CH
Het). 13C NMR spectrum, δ, ppm: 18.8 ((CH2)2(CH2)2(CH2)2);
22.6, 22.8 (CH3); 24.1 (CH2CH2(CH2)2CH2CH2); 29.6 (CH2(CH2)4CH2);
110.3 (C-3 furoxan); 117.8, 127.5 (C Het); 152.4 (C-4
furoxan); 166.2 (CS). Found, m/z: 531.1576 [M+H]+.
C22H27N8O4S2. Calculated, m/z: 531.1591. Found, %:
C 49.82; H 4.91; N 21.10; S 12.11. C22H26N8O4S2.
Calculated, %: C 49.80; H 4.94; N 21.12; S 12.09.
2,2'-{(Hexane-1,6-diyl)bis[(5-oxido-1,2,5-oxadiazole-
4,3-diyl)sulfanediyl]}bis(1,3,4-thiadiazol-2-amine) (3ap).
Yield 264 mg (51%), dark-yellow powder, mp 285–287°C.
1H NMR spectrum, δ, ppm (J, Hz): 1.16 (4H, br. s,
(CH2)2(CH2)2(CH2)2); 1.57 (4H, br. s, CH2CH2(CH2)2CH2CH2);
3.42 (4H, br. s, CH2(CH2)4CH2); 7.97 (4H, br. s, 2NH2).
13C NMR spectrum, δ, ppm: 19.6 ((CH2)2(CH2)2(CH2)2);
23.9 (CH2CH2(CH2)2CH2CH2); 28.6 (CH2(CH2)4CH2);
109.6 (C-3 furoxan); 153.2 (C-4 furoxan); 160.2 (CNH2);
172.8 (SCS). Found, m/z: 517.0306 [M+H]+. C14H17N10O4S4.
Calculated, m/z: 517.0311. Found, %: C 32.52; H 3.08;
N 27.15; S 24.80. C14H16N10O4S4. Calculated, %: C 32.55;
H 3.12; N 27.11; S 24.83.
CH3); 7.42 (1H, d, J = 8.4, H-4 Het); 7.61–7.66 (3H, m,
3
H-3,4,5 Ph); 7.92 (1H, d, J = 8.4, H-3 Het); 8.11 (2Н, d,
3J = 6.8, H-2,6 Ph); 8.67 (1H, s, H-6 Het). 13C NMR
spectrum, δ, ppm: 23.4 (CH3); 108.2 (C-3 furoxan); 121.6,
124.0, 126.7, 128.5, 129.1, 130.9, 141.1, 147.6, 162.3
(C Ph, C Het); 156.3 (C-4 furoxan). Found, m/z: 270.0877
[M+H]+. C14H12N3O3. Calculated, m/z: 270.0873. Found, %:
C 62.49; H 4.05; N 15.57. C14H11N3O3. Calculated, %:
C 62.45; H 4.12; N 15.61.
6-Methyl-2-nitro-3-[(5-oxido-4-phenyl-1,2,5-oxadiazol-
3-yl)oxy]pyridine (7b). Yield 254 mg (81%), bright-yellow
powder, mp 141–143°C. 1H NMR spectrum, δ, ppm (J, Hz):
2.62 (3Н, s, CH3); 7.62–7.66 (3H, m, H-3,4,5 Ph); 7.91
(1H, d, 3J = 8.4, H-4 Het); 8.07 (2Н, d, 3J = 6.4, H-2,6 Ph);
3
8.44 (1H, d, J = 8.4, H-3 Het). 13C NMR spectrum, δ,
ppm: 22.9 (CH3); 107.9 (C-3 furoxan); 121.1, 126.5, 129.1,
130.8, 131.1, 134.7, 138.8, 147.5, 161.4 (C Ph, C Het);
156.5 (C-4 furoxan). Found, %: C 53.47; H 3.23; N 17.77.
C14H10N4O5. Calculated, %: C 53.51; H 3.21; N 17.83.
8-[(5-Oxido-4-phenyl-1,2,5-oxadiazol-3-yl)oxy]quino-
line (7c). Yield 250 mg (82%), light-yellow powder, mp
1
167–169°C (decomp.). H NMR spectrum, δ, ppm (J, Hz):
7.63–7.75 (5H, m, H-3,4,5 Ph, H-3,6 Het); 7.98 (1H, d,
3
3J = 7.4, H-4 Het); 8.04 (1H, d, J = 7.4, H-5 Het); 8.25
(2Н, d, 3J = 7.1, H-2,6 Ph); 8.52 (1H, d, 3J = 8.2, H-7 Het);
8.93 (1H, br. s, H-2 Het). 13C NMR spectrum, δ, ppm:
108.0 (C-3 furoxan); 120.9, 121.8, 122.6, 126.6, 126.8,
127.1, 129.2, 129.6, 131.0, 136.5, 139.2, 148.4, 163.0
(C Ph, C Het); 151.2 (C-4 furoxan). Found, %: C 66.83;
H 3.69; N 13.72. C17H11N3O3. Calculated, %: C 66.88;
H 3.63; N 13.76.
1,2-Bis(5-propyl-5H-[1,2,4]triazino[5,6-b]indol-3-yl)
disulfide (5b). A suspension of thiol 2d (0.17 g, 0.7 mmol)
in anhydrous MeCN (2 ml) was stirred and treated with
Et3N (0.10 ml, 0.7 mmol) or DBU (0.11 ml, 0.7 mmol).
Furoxan 1e was added to the obtained mixture after 10 min,
and stirring was continued for 40 min until complete
conversion of the starting furoxan 1e (control by TLC,
eluent CHCl3). The reaction mixture was then diluted with
H2O (10 ml), the precipitate formed was filtered off,
washed with water and acetonitrile, and air-dried. Yield
190–210 mg (56–63%), bright-red powder that remained
5-Bromo-8-[(5-oxido-4-phenyl-1,2,5-oxadiazol-3-yl)-
oxy]quinoline (7d). Yield 334 mg (87%), yellow powder,
1
mp 188–190°C (decomp.). H NMR spectrum, δ, ppm (J,
Hz): 7.61–7.68 (3H, m, H-3,4,5 Ph); 7.78–7.83 (1H, m,
3
H-3 Het); 7.97 (1H, d, J = 8.2, H-6 Het); 8.11 (1H, d,
3
3J = 8.2, H-7 Het); 8.22 (2Н, d, J = 6.4, H-2,6 Ph); 8.60
1
3
3
unchanged upon heating to 300°C. H NMR spectrum, δ,
(1H, d, J = 8.6, H-4 Het); 9.00 (1Н, d, J = 8.6, H-2 Het).
13C NMR spectrum, δ, ppm: 108.6 (C-3 furoxan); 119.1,
121.6, 121.9, 124.1, 126.7, 128.3, 129.2, 130.3, 131.1, 135.6,
140.0, 148.2, 163.4 (C Ph, C Het); 152.1 (C-4 furoxan). Found,
m/z: 407.9778 [M(81Br)+Na]+, 405.9798 [M(79Br)+Na]+.
C17H10BrN3NaO3. Calculated, m/z: 407.9777, 405.9798.
Found, %: C 53.11; H 2.67; Br 20.74; N 10.88.
C17H10BrN3O3. Calculated, %: C 53.15; H 2.62; Br 20.80;
N 10.94.
ppm (J, Hz): 0.90 (6H, t, 3J = 6.8, 2CH3); 1.72–1.77 (4H,
m, 2CH3CH2); 4.03–4.07 (4H, m, 2NCH2); 7.75 (2H, br. s,
3
H Het); 7.90 (4H, br. s, H Het); 8.35 (2H, d, J = 7.3,
H Het). 13C NMR spectrum, δ, ppm: 11.2 (CH3); 20.7
(CH3CH2); 42.0 (NCH2); 117.0, 117.8, 120.9, 122.7, 123.1,
130.7, 141.7, 143.9, 154.0 (C). Found, m/z: 487.1491
[M+H]+. C24H23N8S2. Calculated, m/z: 487.1482.
Preparation of hetaryloxyfuroxans 7a–j (General
method). DBU (0.15 ml, 1 mmol) was added dropwise at
room temperature to a stirred solution of the respective
hydroxy heterocycle 6a–e (1 mmol) in anhydrous MeCN
(2 ml). The obtained solution was treated after 10 min by
3-Phenyl-4-(1Н-pyrazol-4-yloxy)-1,2,5-oxadiazole 2-oxide
(7e). Yield 166 mg (68%), white powder, mp 70–72°C
1
(decomp.). H NMR spectrum, δ, ppm (J, Hz): 7.54 (3H,
3
br. s, H-3,4,5 Ph); 8.07 (2Н, d, J = 6.6, H-2,6 Ph); 8.26
184

Chemistry of Heterocyclic Compounds 2015, 51(2), 176–186
(1H, s, H-5 Het); 8.73 (1H, s, H-3 Het); 12.92 (1H, br. s,
2NH). 13C NMR spectrum, δ, ppm: 21.3 ((CH2)2(CH2)2(CH2)2);
24.4 (CH2CH2(CH2)2CH2CH2); 27.9 (CH2(CH2)4CH2); 109.2
(C-3 furoxan); 134.6, 138.1, 160.3 (C Het); 151.2 (C-4
furoxan). Found, %: C 45.89; H 4.37; N 26.81. C16H18N8O6.
Calculated, %: C 45.93; H 4.34; N 26.78.
NH). 13C NMR spectrum, δ, ppm: 107.9 (C-3 furoxan);
126.5, 128.7, 129.0, 130.9 (C Ph); 135.8, 138.5, 161.1
(C Het); 151.9 (C-4 furoxan). Found, m/z: 243.0575 [M–H]+.
C11H7N4O3. Calculated, m/z: 243.0513. Found, %: C 54.07;
H 3.34; N 22.89. C11H8N4O3. Calculated, %: C 54.10;
H 3.30; N 22.94.
The work was performed with financial support from the
Russian Science Foundation (grant 14-50-00126).
5-[(4-Benzyl-5-oxido-1,2,5-oxadiazol-3-yl)oxy]-2-methyl-
pyridine (7f). Yield 204 mg (72%), white powder, mp
1
References
77–79°C. H NMR spectrum, δ, ppm (J, Hz): 2.55 (3Н,
s, CH3); 4.12 (2H, s, CH2Ph); 7.34 (5H, s, H Ph); 7.44 (1H,
1. Fershtat, L. L.; Epishina, M. A.; Kulikov, A. S.; Makhova, N. N.
Mendeleev Commun. 2015, 25, 36.
3
3
d, J = 8.6, H-4 Het); 7.88 (1H, d, J = 8.6, H-3 Het); 8.63
(1H, s, H-6 Het). 13C NMR spectrum, δ, ppm: 23.1 (CH3),
29.6 (CH2Ph); 108.9 (C-3 furoxan); 121.9, 124.6, 126.8,
128.3, 129.3, 130.6, 141.2, 147.4, 162.1 (C Ph, C Het);
149.3 (C-4 furoxan). Found, %: C 63.64; H 4.58; N 14.86.
C15H13N3O3. Calculated, %: C 63.60; H 4.63; N 14.83.
3-Benzyl-4-(1Н-pyrazol-4-yloxy)-1,2,5-oxadiazole 2-oxide
(7g). Yield 139 mg (54%), white powder, mp 66–68°C
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1
(decomp.). H NMR spectrum, δ, ppm (J, Hz): 4.17 (2H, s,
CH2Ph); 7.31 (5H, s, H Ph); 8.21 (1H, s, H-5 Het); 8.69 (1H, s,
H-3 Het); 12.87 (1H, br. s, NH). 13C NMR spectrum, δ, ppm:
29.2 (CH2Ph); 110.8 (C-3 furoxan); 126.8, 128.5, 129.3, 131.8
(C Ph); 135.2, 138.9, 161.3 (C Het); 149.6 (C-4 furoxan).
Found, %: C 55.76; H 3.93; N 21.66. C12H10N4O3. Calculated,
%: C 55.81; H 3.90; N 21.70.
3,3'-(Hexane-1,6-diyl)bis[(5-oxido-1,2,5-oxadiazole-
4,3-diyl)oxy]}bis(6-methylpyridine) (7h). Yield 183 mg
1
(78%), white powder, mp 92–94°C. H NMR spectrum, δ,
ppm (J, Hz): 1.36 (4H, br. s, CH2CH2CH2CH2CH2CH2);
1.64 (4H, br. s, CH2CH2(CH2)2CH2CH2); 2.53 (6Н, s,
2CH3); 2.62 (4H, br. s, CH2(CH2)4CH2); 7.37 (2H, d,
3J = 8.6, H-4 Het); 7.81 (2H, d, 3J = 8.6, H-3 Het); 8.56 (2H,
s, H-6 Het). 13C NMR spectrum, δ, ppm: 21.3 ((CH2)2(CH2)2(CH2)2);
23.4 (2CH3); 24.1 (CH2CH2(CH2)2CH2CH2); 27.8
(CH2(CH2)4CH2); 109.8 (C-3 furoxan); 124.0, 128.1, 140.8,
147.6, 163.1 (C Het); 156.1 (C-4 furoxan). Found, %:
C 56.44; H 5.09; N 17.98. C22H24N6O6. Calculated, %:
C 56.40; H 5.16; N 17.94.
8,8'-(Hexane-1,6-diyl)bis[(5-oxido-1,2,5-oxadiazole-
4,3-diyl)oxy]}bis(5-bromoquinoline) (7i). Yield 247 mg
(71%), yellow powder, mp 173–175°C. 1H NMR spectrum,
δ, ppm (J, Hz): 1.42 (4H, br. s, (CH2)2(CH2)2(CH2)2); 1.77 (4H,
br. s, CH2CH2(CH2)2CH2CH2); 2.71 (4H, t, 3J=6.8,
CH2(CH2)4CH2); 7.69–7.74 (2H, m, H-3 Het); 7.80 (2H, d,
3
3J = 8.1, H-6 Het); 8.02 (2H, d, J = 8.1, H-7 Het); 8.51
3
(2H, d, J = 8.3, H-4 Het); 8.91 (2Н, br. s, H-2 Het).
13C NMR spectrum, δ, ppm: 21.4 ((CH2)2(CH2)2(CH2)2);
24.1 (CH2CH2(CH2)2CH2CH2); 27.8 (CH2(CH2)4CH2);
109.6 (C-3 furoxan); 118.8, 121.3, 123.9, 128.1, 130.1,
135.3, 139.9, 148.2, 163.8 (C Het); 151.6 (C-4 furoxan).
Found, %: C 48.11; H 3.24; Br 22.85; N 11.99. C28H22Br2N6O6.
Calculated, %: C 48.16; H 3.18; Br 22.88; N 12.03.
3,3'-(Hexane-1,6-diyl)bis[(4-(1Н-pyrazol-4-yloxy)-1,2,5-oxa-
diazole] 2,2'-dioxide (7j). Yield 127 mg (61 %), white powder,
1
mp 91–93°C (decomp.). H NMR spectrum, δ, ppm (J, Hz):
1.36 (4H, br. s, (CH2)2(CH2)2(CH2)2); 1.69 (4H, br. s,
CH2CH2(CH2)2CH2CH2); 2.76 (4H, t, 3J=6.6, CH2(CH2)4CH2);
8.19 (2H, s, H-5 Het); 8.67 (2H, s, H-3 Het); 12.96 (2H, br. s,
185

Chemistry of Heterocyclic Compounds 2015, 51(2), 176–186
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