3-(α-Chlorobenzyl)quinoxalin-2(1H)-ones as Versatile Reagents for the Synthesis of 3-Benzylquinoxalin-2(1H)-ones and Thiazolo[3,4-a]quinoxalin-4(5H)-ones

Article abstract of DOI:10.1002/jhet.3616

Facile and efficient methods for the synthesis of 3-benzylquinoxalin-2(1H)-ones and thiazolo[3,4-a]quinoxalin-4(5H)-ones by the reaction of the readily available 3-(α-chlorobenzyl)quinoxalin-2(1H)-ones and thiourea have been developed, with multiple roles

Full text of DOI:10.1002/jhet.3616

Month 2019
3-(α-Chlorobenzyl)quinoxalin-2(1H)-ones as Versatile Reagents for the
Synthesis of 3-Benzylquinoxalin-2(1H)-ones and Thiazolo[3,4-a]
quinoxalin-4(5H)-ones
Vakhid A. Mamedov,a,b
Nataliya A. Zhukova,a Victor V. Syakaev,a Tat’yana N. Beschastnova,a
*
Milyausha S. Kadyrova,a,b Anastasiya O. Isaeva,b Sevil V. Mamedova,b Elena L. Gavrilova,b Shamil K. Latypov,a and
Oleg G. Sinyashina,b
aA.E. Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of the Russian Academy of
Sciences, Arbuzov Street 8, 420088, Kazan, Russian Federation
bKazan National Research Technological University, Karl Marx Street 68, 420015, Kazan, Russian Federation
*E-mail: mamedov@iopc.ru
Received March 12, 2019
DOI 10.1002/jhet.3616
Published online 00 Month 2019 in Wiley Online Library (wileyonlinelibrary.com).
Facile and efficient methods for the synthesis of 3-benzylquinoxalin-2(1H)-ones and thiazolo[3,4-a]
quinoxalin-4(5H)-ones by the reaction of the readily available 3-(α-chlorobenzyl)quinoxalin-2(1H)-ones
and thiourea have been developed, with multiple roles of the latter. Possible mechanisms are discussed.
These two-step sequences can be performed in a one-pot manner to produce the desired products in moderate
to high yields.
J. Heterocyclic Chem., 00, 00 (2019).
INTRODUCTION
developed (Scheme 1). The first one is based on
3-(α-cyano)benzylquinoxalin-2(1H)-one 3, which is
converted to the desired 3-BQ 1a by acid hydrolysis via
3-(α-carboxamido)benzylquinoxalin-2(1H)-one 4 [eq. (1)
in Scheme 1] [17]. The second one is based on
4-benzylidene-2-methyloxazol-5(4H)-one 7, which reacts
with o-phenylenediamine (o-PDA) with the direct
formation of 3-BQ 1a [eq. (2) in Scheme 1] [13a]. The
necessary quinoxalinone derivatives for the first method
and oxazole-5(4H)-one for the second method were
synthesized from the ethyl ester of phenyl cyanopyruvic
acid 2 [eq. (1) in Scheme 1] and acetylglycine 6 [eq. (2)
in Scheme 1], respectively. The third method is based
directly on arylpropionate acid derivatives 8, which react
with the o-PDA with the formation of 3-BQs 1 [eq. (3) in
Scheme 1] [13b, 18]. Among these methods, the most
effective one is the second [eq. (2) in Scheme 1], based
on the oxazol-5(4H)-one derivative 7, because the two-
stage synthesis of this compound from glycine and the
last stage of the formation of 3-BQ 1a proceed with good
yields. But, unfortunately, so far, only one compound has
been synthesized by this method. The first method
[eq. (1) in Scheme 1] has also been used for the synthesis
Quinoxaline derivatives[1] display a broad spectrum of
pharmacological activities including insecticides [2],
antimicrobial [3], antibacterial [4], antifungal 4a,
antitubercular [5], anticancer [6], analgesic [4c, 7], anti-
inflammatory [8], and PI3Kα inhibitory properties [9].
Some of the compounds derived from quinoxalines have
been shown to display as antihypertensive agents and
animal growth promoters [10]. Antibacterial, analgesic,
tuberculostatic, and antileukemic activities of separate
condensed quinoxalines have been widely reported [11].
Quinoxaline moieties have been shown to enter into the
composition of biologically active polypeptides such as
levomycin and echinomycin [12]. Recently, a series of 3-
benzyl substituted quinoxalines have been synthesized.
Among them, potential anticancer [13], antimicrobial
[13a], antithrombotic [14] agents, MAO-A inhibitors
[15], and agents for the treatment of tuberculosis [16]
have been found.
Although the importance of this class of compounds
is clear, only three methods of the synthesis of
3-benzylquinoxalin-2(1H)-ones (3-BQs) 1 have been
© 2019 Wiley Periodicals, Inc.

V. A. Mamedov, N. A. Zhukova, V. V. Syakaev, T. N. Beschastnova, M. S. Kadyrova,
A. O. Isaeva, S. V. Mamedova, E. L. Gavrilova, S. K. Latypov, and O. G. Sinyashin
Vol 000
Scheme 1. Known methods for the synthesis of 3-benzylquinoxalin-2(1H)-ones.
of only one compound. As for the third method [eq. (3) in
Scheme 1], it could be most effective if the derivatives of
arylpyruvic acid 8 were available. Unfortunately, only
phenylpyruvic acid is commercially available (the price
works out at €49.30 for 5 g and €61.45 for 5 g of
phenylpyruvic acid sodium salt) [19], and the synthesis
of other aryl derivatives of pyruvic acid 8 is multistage
[20–22].
Nakamura and co-workers [23] noted that
α-(methylthio)-ketones and esters are easily reduced to the
corresponding carbonyl compound by MeSÀ anion. α-
Halo or α,α-dihalo carbonyl compounds are analogously
reduced with thiolate anion, presumably via the
corresponding sulfides [eq. (1) in Scheme 2]. Israel and
co-workers [24] also reported a rapid and unexpected
reductive dehalogenation of 2-iodo-1-phenylethan-1-one
in the presence of alkanethiols or thiophenol (2 equiv)
with K2CO3 in ethanol at room temperature [eq. (2) in
Scheme 2]. Veale and co-workers described the
debromination and nucleophilic substitution of
thiophenols, whose electron donating or withdrawing
properties resulted in wide variations in the degree of
nucleophilic substitution and dehalogenation products,
correspondingly [eq. (3) in Scheme 2] [25].
Earlier in a number of our works, we showed [26] that
3-(α-chlorobenzyl)quinoxalin-2(1H)-ones [27] behave as
hetero-analogues of α-haloketones in the reactions with
nucleophilic reagents. Therefore, we assumed that
using the methods [23–25] mentioned earlier, their
corresponding alkyl derivatives can be synthesized by the
reductive dehalogenation of 9. Unfortunately, attempts to
obtain 3-BQ 1a from 3-(α-chlorobenzyl)quinoxalin-2(1H)-
one under the reductive dehalogenation conditions of α-
haloketones, shown in Scheme 3, were unsuccessful. Each
time, the reactions took place with the formation of a
mixture of difficult-to-separate products, and the desired
product in these mixtures was present in trace amounts.
RESULTS AND DISCUSSION
3-(bromoacetyl)coumarin with
a
larch number of
Reactions of quinoxalin-2(1H)-ones 9a–d with thiourea
when heated at reflux in dioxane for 4 h lead to the
expected 3-BQs 1a–d in 49–78% yields (Table 1,
entries 1–4). The reactions of quinoxalin-2(1H)-ones
9e–h under similar conditions lead to the tautomeric
mixture of the corresponding carbamimidothioate
Scheme 2. Known methods for the reductive dehalogenation of α-
haloketones.
10e–h,
spiro[quinoxaline-2,4′-thiazolidin]-3(4H)-one
11e–h, and spiro[quinoxaline-2,4′-thiazol]-3(4H)-one
12e–h hydrochlorides in overall yields 71–89%, in the
percentage ratio, as shown in Table 1 (entries 5–8). It
should be pointed out that in the latter cases along with
the 10e–h/11e–h/12e–h tautomers, there has been
observed the formation of trace amounts of the targets
3-BQs 1e–g [R═H, Ar═C6H4Cl-4 (e), C6H3Cl2–2,4 (f),
C6H4Br-4 (g)] and 1h (R═Cl, Ar═Ph) (Table 1, entries
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3-Benzylquinoxalin-2(1H)-ones
Scheme 3. Proposed mechanism for the synthesis of compounds 1.
Table 1
Pathways of the reactions of 3-(α-chlorobenzyl)quinoxalin-2(1H)-ones 9a–h with thiourea in dioxane.
Entry
9
R
R
Ar
1
Yield (%)a
10/11/12
10/11/12 ratiob
Overall yield of 10/11/12 (%)a
1
2
3
4
5
6
7
8
9a
9b
9c
9d
9e
9f
H
H
H
H
H
H
H
Cl
H
H
H
H
H
H
H
Cl
Ph
1a
1b
1c
1d
1e
1f
78
71
69
49
n/i
n/i
n/i
n/i
10b/11b/12b
10b/11b/12b
10c/11c/12c
10d/11d/12d
10e/11e/12e
10f/11f/12f
—
—
—
—
—
—
—
82
80
89
71
4-FC6H4
2-FC6H4
3-O2NC6H4
4-ClC6H4
2,4-Cl2C6H3
4-BrC6H4
Ph
—
29:28:43
29:24:47
31:28:41
4:37:59
9g
9h
1g
1h
10g/11g/12g
10h/11h/12h
n/i, not isolated.
aIsolated yield.
1
bThe percentage ratio of 10/11/12 was determined from the H NMR spectra.
5–8). This is evident by thepresence of signals 3-BQs 1e–h
makes it possible to identify and fully assign the peaks
of three compounds, despite the complexity and
along with the signals of tautomers 10e-h/11e-h/12e-h in
1
1
the H NMR spectra of evaporated in vacuum to dryness
partial overlapping of the peaks in both the H and 13C
of the reaction mixtures quinoxalin-2(1H)-ones 9e–h and
thiourea. The singlet signals of protons of methylene
group in the region 4.09–4.26 ppm indicate to the
presence of 3-BQs 1e–h in the mixture of products. In
addition, in the case of the reaction of quinoxalin-2(1H)-
one 9h with thiourea, the formation of the
1-iminothiazolo[3,4-a]quinoxalin-4(5H)-one 13 as a by-
product in 19% yield has also been obtained (Table 1).
NMR spectra of solutions of the mixture of tautomers 10/
11/12 in DMSO-d6 indicate the presence of three
compounds. The use of two-dimensional techniques
NMR spectra (see the example of the 10e/11e/12e spectra
in the Supporting Information). In the NMR spectra of
these three compounds, namely, carbamimidothioate
10e,
spiro[quinoxalinethiazolidin]one
11e,
and
spiro[quinoxalinethiazol]one 12e hydrochlorides, we can
distinguish characteristic signals that make it possible to
easily identify their percentage ratio in the solution. These
are the singlet peaks of the methine groups for structure
10e, СH(α) (δ 1Н 6.76–6.91; 13С 50.2 ppm); for
1
structure 11e, CH(5′) (δ Н 5.31; 13С 58.5 ppm); and for
1
structure 12e, CH(5′) (δ Н 5.85; 13С 55.8 ppm). The
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

V. A. Mamedov, N. A. Zhukova, V. V. Syakaev, T. N. Beschastnova, M. S. Kadyrova,
A. O. Isaeva, S. V. Mamedova, E. L. Gavrilova, S. K. Latypov, and O. G. Sinyashin
Vol 000
presence of the latter in two forms is further confirmed by
the peaks of quaternary spiro-carbon atom C(4′) at 84.2
and 82.0 ppm, respectively. This eliminates the need to
carry out laborious work on the complete identification of
all the peaks of the mixture of three compounds.
Therefore, for tautomers 10/11/12, only the chemical
tautomeric mixtures of 10a–g/11a–g/12a–g, formed in the
first stage of the process (Table 3, entries 4–10).
The formation of 3-BQs 1a–g from carbamimidothioate
hydrochlorides 10a–g proceeds under the action of the
chloride anion on the protonated sulfur atom by
hydrochloric acid in intermediate A with the cleavage of
the Cα─S bond with the generation of the anion B,
which was stabilized by the protonation with hydrochloric
acid with the involvement of carbamimidoylsulfonium
chloride. In this case, the chlorine gas and thiourea are
formed as by-products (Scheme 3).
1
shifts of the identification peaks in the H NMR spectra
and the ratio of the solution components are presented in
the Experimental section, and the NMR spectra are given
in the Supporting Information.
The synthesis of the tautomeric mixtures of
carbamimidothioate
10a–h,
spiro[quinoxaline-2,4′-
Unlike the tautomeric mixtures 10b–g/11b–g/12b–g, the
tautomeric mixture 10h/11h/12h when heated at reflux in
EtOH/HCl for 5 h does not lead to BQ 1h, as expected,
but to the spiro-derivative 11h in quantitative yield
(Scheme 6). Heating of the latter at reflux in Ac2O for
thiazolidin]-3(4H)-one 11a–h, and spiro[quinoxaline-2,4′-
thiazol]-3(4H)-one 12a–h hydrochlorides was also carried
out by the reaction of quinoxalin-2(1H)-ones 9a–h with
thiourea in methanol at room temperature (Table 2, entries
1–3, 5, 6, and 8) or at room temperature, followed by
heating at 45°C (Table 2, entry 4) or 50°C (Table 2, entry 7).
On the example of tautomeric mixtures 10d/11d/12d,
10f/11f/12f, and 10g/11g/12g, it was shown that boiling
the latter in EtOH in the presence of HCl leads to the
formation of the corresponding 3-BQs 1d,f,g (Table 3,
entries 1–3). However, a more convenient method of
obtaining 3-BQs 1 appears to be a one-pot two-stage
process, without any isolation of the intermediate
1.5
quinoxalin-4(5H)-one 14a in a 83% yield as a result of
the simultaneous occurrence of intramolecular
h gives 1-acetylimino-7,8-dichlorothiazolo[3,4-a]
cyclocondensation and acylation processes. Note that
compound 14a was also obtained in a 95% yield when
the mixture of 10h/11h/12h was heated under the same
condition (Scheme 4).
With this result in hand, we next carried out the
rearrangements of tautomeric mixtures of 10a–g/11a–g/
Table 2
Reactions of 3-(α-chlorobenzyl)quinoxalin-2(1H)-ones 9a–h with thiourea in methanol.
Entry
9
R
Ar
Time
8 h
10/11/12
10/11/12 ratiod
Overall yield (%)a
1
2
3
4
5
6
7
8
9a
9b
9c
9d
9e
9f
H
H
H
H
H
H
H
Cl
Ph
10a/11a/12a
10b/11b/12b
10c/11c/12c
10d/11d/12d
10e/11e/12e
10f/11f/12f
32:28:40
25:25:50
31:28:41
30:25:45
35:25:40
30:26:44
31:31:38
3:35:62
88
85
77
91
88
80
89
75
4-FC6H4
2-FC6H4
3-O2NC6H4
4-ClC6H4
2,4-Cl2C6H3
4-BrC6H4
Ph
6 h
7 h
b
—
22 h
11 days
c
9g
9h
—
10g/11g/12g
10h/11h/12h
6 days
aIsolated yield.
bReaction conditions: MeOH, rt, 14 h → 45°C, 2 h.
cReaction conditions: MeOH, rt, 3 days → 50°C, 5.5 h.
1
dThe percentage ratio of 10/11/12 was determined from the H NMR spectra.
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3-Benzylquinoxalin-2(1H)-ones
Table 3
Synthesis of 3-benzylquinoxalin-2(1H)-ones 1.
Entry
Substrate
Ar
Method
Time
1
Yield (%)a
1
2
3
4
10d/11d/12d
10f/11f/12f
10g/11g/12g
9a
3-O2NC6H4
2,4-Cl2C6H3
4-BrC6H4
Ph
A
A
A
B
8.5 h
15 h
11 h
1d
1f
1g
1a
88
73
77
78
(1) 8 h
(2) 8 h
5
6
9b
9c
4-FC6H4
2-FC6H4
B
B
(1) 8.5 h
(2) 5.5 h
(1) 7 h
1b
1c
83
83
(2) 5.5 h
(1) and (2)b
(1) 3 days
(2) 8 h
7
8
9d
9e
3-O2NC6H4
4-ClC6H4
B
B
1d
1e
91
87
9
9f
2,4-Cl2C6H3
4-BrC6H4
B
B
(1) 11 days
(2) 8 h
1f
79
81
10
9g
(1) and (2)c
1g
aIsolated yield.
bReaction conditions: (1) MeOH, 45°C, 19 h; (2) n-BuOH/HCl, reflux, 19 h.
cReaction conditions: (1) MeOH, rt, 3 days → 50°C, 6.5 h → reflux, 1.5 h; (2) EtOH/HCl, reflux, 8 h.
12a–g when heating at reflux in Ac2O. As a result, the
corresponding 1-acetylimino-3-arylthiazolo[3,4-a]
nucleophilic attack by the nitrogen atom of the pyrazine
ring of C, D, and E on the isothiouronium carbon atom
leads to the closure of the thiazole ring on the a side of
quinoxaline with the formation of F, G, and H. In these
cases, thiazolo[a]annelation can proceed with the
elimination of either AcNH2 or Ac2NH. The final product
is produced either directly from F or after acylation of H
and I (Scheme 6).
quinoxalin-4(5H)-ones 14b–h have been obtained in high
to quantitative yields (Scheme 5). The characteristic
signal indicating the formation of a thiazolo[3,4-a]
quinoxalin-4(5H)-one system in 1H NMR spectra is a
doublet of doublet (J = ~8.0, ~1.0 Hz) signal of H(9),
which resonates at ~10.0 ppm separately from other
aromatic protons [28]. This indicates the formation of a
stimulated intramolecular hydrogen bonding involving
H(9) and a nitrogen atom of the imine group.
CONCLUSIONS
As to the mechanism of thiazolo[a]annelation in
all probability, it proceeds via the open-chain N-acylated
carbamimidothioate hydrochloride tautomeric form C
produced by the action of acetic anhydride on
In summary, we have developed facile and efficient
methods for the synthesis of highly functionalized
3-benzylquinoxalin-2(1H)-ones
and
thiazolo[3,4-a]
the
[(quinoxalin-2(1H)-on-2-yl)(aryl)methyl]
quinoxalin-4(5H)-ones from readily accessible starting
materials. These two-step sequences can be realized into
a one-pot process, by evaporating the reaction mixture
before performing the ensuing chloride anion-mediated
reductive cleavage of (quinoxalin-2(1H)-on-2-yl)(aryl)
isothiouronium chloride 10. Further acylation took place
on the more nucleophilic isothiouronium nitrogen atom
with the formation of a diacylderivative D that contains a
high electrophilic isothiouronium carbon atom. The
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

V. A. Mamedov, N. A. Zhukova, V. V. Syakaev, T. N. Beschastnova, M. S. Kadyrova,
A. O. Isaeva, S. V. Mamedova, E. L. Gavrilova, S. K. Latypov, and O. G. Sinyashin
Vol 000
Scheme 4. The behavior of tautomeric mixture 10h/11h/12h in boiling at reflux in EtOH/HCl and Ac2O.
spectra were obtained in a 5-mm gradient inverse broad
Scheme 5. Synthesis of 1-acetyliminothiazolo[3,4-a]quinoxalin-4(5H)-
ones 14b–h.
band probehead. Chemical shifts (δ in ppm) are given
1
from internal solvent, DMSO-d6 (δ, H, 2.49 ppm; 13C,
39.5 ppm), and 15N are referenced relative to external
CD3NO2 (380.2 ppm).
General
procedures
for
the
synthesis
of
3-benzylquinoxalin-2(1H)-ones 1a–g. Method A.
A
mixture of tautomers 10d,f,g/11d,f,g/12d,f,g (1.12 mmol)
in EtOH/HCl (1.3/1.0, v/v) was heated at reflux with
stirring for 8.5–15 h (Table 2). Gradually, a precipitate
was formed, which was filtered off, washed with water
(3 × 5 mL), and dried in air to afford analytically pure
samples of 1d,f,g, respectively.
Method B. A mixture of thiourea (0.15 g, 1.97 mmol)
methyl carbamimidothioate hydrochlorides in the first case
and acetic anhydride-mediated thiazoloannulation in the
second. We assume that these protocols have a potential
in the synthesis of various quinoxaline scaffolds, which
are of considerable interest as potential biological active
compounds or pharmaceuticals in synthetic and medicinal
chemistry.
and the corresponding quinoxalin-2(1H)-ones 9a–g
(1.79 mmol) in dry MeOH (25 mL) was stirred at room
temperature for an appropriate time (Table 3), and the
reaction mixture was left overnight at room temperature
and then was evaporated in vacuum to dryness, and the
residue was dissolved with EtOH/HCl (1.3/1.0, v/v). The
resulting reaction mixture was heated at reflux with
stirring for 5.5–8 h. Gradually, a precipitate was formed,
which was filtered off, washed with water (3 × 5 mL),
and dried in air to afford analytically pure samples of
corresponding benzylquinoxalin-2(1H)-ones 1a–g.
Method C. A mixture of thiourea (0.10 g, 1.31 mmol)
and the corresponding quinoxalin-2(1H)-ones 9b–d
(1.19 mmol) in dry dioxane (10 mL) was heated at reflux
with stirring for 4 h. The solution was hot decanted and
allowed to cool to room temperature, and a beige
precipitate was removed by filtration to afford
analytically pure samples of 1b–d.
EXPERIMENTAL
General. Melting points were determined on a Boetius
melting point apparatus. IR spectra were recorded on a
Tensor 27 (Bruker) FT-IR spectrometer with KBr pellets.
NMR experiments were carried out with Bruker
spectrometers AVANCE (III)-500 [500.1 MHz (1H),
125.8 MHz (13C), 50.7 MHz (15N)] equipped with a
pulsed gradient unit capable of producing magnetic field
pulse gradients in the z-direction of 53.5 G cmÀ1. All the
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3-Benzylquinoxalin-2(1H)-ones
Scheme 6. Proposed mechanism for the synthesis of compounds 14.
J = 1.2 Hz, 1H, H5-Q), 12.37 (s, 1H, NH1-Q); 13C{1H}
NMR (126 MHz, DMSO-d6): δ 38.1 (Cα), 115.0 (d,
JCF = 21.0 Hz, C3/C5-Ar), 115.3 (C8-Q), 123.2 (C6-Q),
128.2 (C5-Q), 129.8 (C7-Q), 130.9 (d, JCF = 8.1 Hz,
C2/C6-Ar), 131.6 (C4a-Q), 131.9 (C8a-Q), 133.5 (d,
JCF = 3.2 Hz, C1-Ar), 154.5 (C3-Q), 160.2 (C2-Q), 161.3
(d, JCF = 246.5 Hz, C4-Ar); IR (KBr, cmÀ1): ν 2969,
2846, 2714, 1665, 1609, 1564, 1511, 1224, 1157, 1141,
1019, 889, 819, 753, 589, 482, 467; Anal. Calcd for (%)
C15H11FN2O: C, 70.86; H, 4.36; N, 11.02. Found (%) C,
71.05; H, 4.51; N, 11.12.
3-Benzylquinoxalin-2(1H)-one (1a).
Beige powder;
1
0.33 g, 78% yield (Method B), mp 198–200°С; H NMR
(500 MHz, DMSO-d6): δ 4.12 (s, 2H, CHα), 7.20 (dd,
J = 7.3 Hz, J = 7.3 Hz, 1H, H4-Ar), 7.22–7.30 (m, 4H,
H6-Q, H3/H5-Ar, H8-Q), 7.33 (d, J = 7.2 Hz, 2H,
H2/H6-Ar), 7.48 (ddd, J = 7.6 Hz, J = 7.4 Hz,
J = 1.0 Hz, 1H, H7-Q), 7.71 (dd, J = 7.6 Hz, J = 1.0 Hz,
1H, H5-Q), 12.36 (s, 1H, NH1-Q); 13C{1H} NMR
(126 MHz, DMSO-d6): δ 38.9 (Cα), 115.2 (C8-Q), 123.1
(C6-Q), 126.3 (C4-Ar), 128.2 (C5-Q, 3/C5-Ar), 129.7
(C2/C6-Ar, C7-Q), 131.6 (C4a-Q), 131.9 (C8a-Q), 137.4
(C1-Ar), 154.5 (C3-Q), 160.3 (C2-Q); IR (KBr, cmÀ1): ν
2960, 2832, 2716, 1661, 1559, 1486, 1434, 911, 753,
700, 600, 581; Anal. Calcd for (%) C15H12N2O: C,
76.25; H, 5.12; N, 11.86. Found (%) C, 76.45; H, 4.95;
N, 11.99.
3-(2-Fluorobenzyl)quinoxalin-2(1H)-one (1c).
Beige
powder; 0.38 g, 83% yield (Method B); 0.21 g, 69%
1
yield (Method C); mp 224–226°С; H NMR (500 MHz,
DMSO-d6): δ 4.17 (s, 2H, CHα), 7.13 (dd, JHH = 7.8 Hz,
JHF = 1.4 Hz, 1H, H5-Ar), 7.16 (dd, JHF = 10.4 Hz,
JHH = 7.8 Hz, 1H, H3-Ar), 7.25 (ddd, J = 8.0 Hz,
J = 7.8 Hz, J = 1.3 Hz, 1H, H6-Q), 7.26–7.36 (m, 3H,
H4-Ar, H8-Q, H6-Ar), 7.48 (ddd, J = 8.0 Hz, J = 7.8 Hz,
J = 1.3 Hz, 1H, H7-Q), 7.63 (dd, J = 8.0 Hz, J = 1.3 Hz,
1H, H5-Q), 12.41 (s, 1H, NH1-Q); 13C{1H} NMR
3-(4-Fluorobenzyl)quinoxalin-2(1H)-one (1b).
Dirty-
(126 MHz, DMSO-d6):
δ
32.1 (Cα), 115.2 (d,
beige powder; 0.38 g, 83% yield (Method B); 0.21 g,
71% yield (Method C); mp 218–220°С; 1H NMR
(500 MHz, DMSO-d6): δ 4.11 (s, 2H, CHα), 7.10 (dd,
JHF = 10.4 Hz, JHH = 8.9 Hz, 2H, H3/H5-Ar), 7.27 (ddd,
J = 8.0 Hz, J = 7.8 Hz, J = 1.2 Hz, 1H, H6-Q), 7.28 (d,
J = 8.0 Hz, 1H, H8-Q), 7.36 (dd, JHH = 8.9 Hz,
JHF = 7.3 Hz, 2H, H2/H6-Ar), 7.48 (ddd, J = 8.0 Hz,
J = 7.8 Hz, J = 1.2 Hz, 1H, H7-Q), 7.70 (dd, J = 8.0 Hz,
JCF = 21.8 Hz, C3-Ar), 115.3 (C8-Q), 123.1 (C6-Q),
124.2 (d, JCF = 3.4 Hz, C5-Ar), 124.2 (d, JCF = 15.8 Hz,
C1-Ar), 128.2 (C5-Q), 128.4 (d, JCF = 8.2 Hz, C4-Ar),
129.8 (C7-Q), 131.5 (d, JCF = 11.0 Hz, C6-Ar), 131.5
(C4a-Q), 131.9 (C8a-Q), 154.4 (C3-Q), 159.2 (C2-Q),
160.6 (d, JCF = 244.2 Hz, C2-Ar); IR (KBr, cmÀ1): ν
3104, 3016, 2968, 1664, 1621, 1562, 1492, 1417, 1230,
1105, 1099, 855, 755, 596, 496, 470; Anal. Calcd for (%)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

V. A. Mamedov, N. A. Zhukova, V. V. Syakaev, T. N. Beschastnova, M. S. Kadyrova,
A. O. Isaeva, S. V. Mamedova, E. L. Gavrilova, S. K. Latypov, and O. G. Sinyashin
Vol 000
C15H11FN2O: C, 70.86; H, 4.36; N, 11.02. Found (%) C,
70.73; H, 4.32; N, 11.07.
3-(3-Nitrobenzyl)quinoxalin-2(1H)-one (1d). Dirty-beige
(C3-Q), 158.8 (C2-Q); IR (KBr, cmÀ1): ν 2964, 2894,
2851, 1662, 1559, 1474, 1432, 1106, 860, 810, 766, 579,
472; Anal. Calcd for (%) C15H10Cl2N2O: C, 59.04; H,
3.30; N, 9.18. Found (%) C, 59.23; H, 3.40; N, 9.07.
powder; 0.28 g, 88% yield (Method A); 0.46 g, 91%
yield (Method B); 0.16 g, 49% yield (Method C); mp
3-(4-Bromobenzyl)quinoxalin-2(1H)-one (1g).
Beige
1
258–260°С; H NMR (500 MHz, DMSO-d6): δ 4.29 (s,
powder; 0.27 g, 77% yield (Method A); 0.46 g, 81%
1
2H, CHα), 7.26 (ddd, J = 7.9 Hz, J = 7.7 Hz, J = 1.1 Hz,
1H, H6-Q), 7.29 (dd, J = 7.9 Hz, J = 1.1 Hz, 1H, H8-Q),
7.48 (ddd, J = 7.9 Hz, J = 7.7 Hz, J = 1.1 Hz, 1H, H7-
Q), 7.60 (dd, J = 8.0 Hz, J = 8.0 Hz, 1H, H5-Ar), 7.69
(dd, J = 7.9 Hz, J = 1.1 Hz, 1H, H5-Q), 7.80 (d,
J = 8.0 Hz, 1H, H6-Ar), 8.09 (dd, J = 8.0 Hz,
J = 1.7 Hz, 1H, H4-Ar), 8.21 (br s, 1H, H2-Ar), 12.42 (s,
1H, NH1-Q); 13C{1H} NMR (126 MHz, DMSO-d6): δ
38.4 (Cα), 115.3 (C8-Q), 121.4 (C4-Ar), 123.2 (C6-Q),
123.9 (C2-Ar), 128.3 (C5-Q), 129.7 (C5-Ar), 129.9 (C7-
Q), 131.5 (C4a-Q), 131.9 (C8a-Q), 136.2 (C6-Ar), 139.6
(C1-Ar), 147.7 (C3-Ar), 154.5 (C3-Q), 159.4 (C2-Q); IR
(KBr, cmÀ1): ν 2965, 2841, 1666, 1613, 1529, 1351,
1108, 907, 747, 726, 699, 595, 554, 469; Anal. Calcd for
(%) C15H11N3O3: C, 64.05; H, 3.94; N, 14.94. Found
(%) C, 63.98; H, 3.99; N, 14.90.
yield (Method B); mp 236–238°С; H NMR (500 MHz,
DMSO-d6): δ 4.09 (s, 2H, CHα), 7.26 (ddd, J = 7.9 Hz,
J = 7.7 Hz, J = 1.1 Hz, 1H, H6-Q), 7.28 (d, J = 8.4 Hz,
2H, H2/H6-Ar), 7.28–7.31 (m, 1H, H8-Q), 7.46 (d,
J = 8.4 Hz, 2H, H3/H5-Ar), 7.48 (ddd, J = 7.9 Hz,
J = 7.7 Hz, J = 1.1 Hz, 1H, H7-Q), 7.69 (dd, J = 7.8 Hz,
J = 1.1 Hz, 1H, H5-Q), 12.39 (s, 1H, NH1-Q); 13C{1H}
NMR (126 MHz, DMSO-d6): δ 38.4 (Cα), 115.4 (C8-Q),
119.6 (C4-Ar), 123.3 (C6-Q), 128.3 (C5-Q), 129.9 (C7-
Q), 131.2 (C3/C5-Ar), 131.5 (C2/C6-Ar), 131.6 (C8a-Q),
132.0 (C4a-Q), 136.9 (C1-Ar), 154.4 (C3-Q), 159.9 (C2-
Q); IR (KBr, cmÀ1): ν 2965, 2884, 2824, 1659, 1556,
1482, 1422, 1274, 1071, 1009, 916, 757, 601, 578, 567,
468; Anal. Calcd for (%) C15H11BrN2O: C, 57.16; H,
3.52; N, 8.89. Found (%) C, 57.02; H, 3.43; N, 9.00.
General procedures for the synthesis of tautomeric
3-(4-Chlorobenzyl)quinoxalin-2(1H)-one (1e).
Beige
mixtures 10a–h/11a–h/12a–h. Method A.
A mixture of
powder; 0.46 g, 87% yield (Method B); mp 224–226°С
(ref. [12] 226–227°C); H NMR (500 MHz, DMSO-d6):
thiourea (0.15 g, 1.97 mmol) and the corresponding
quinoxalin-2(1H)-ones 9a–h (1.79 mmol) in dry MeOH
(25 mL) was stirred at room temperature for an
appropriate time (Table 1). The solvent was evaporated to
dryness, and the resulting solid was washed with ethyl
ether (3 × 5 mL) and filtered to afford analytically pure
1
δ 4.12 (s, 2H, CHα), 7.25 (ddd, J = 8.0 Hz, J = 7.8 Hz,
J = 1.0 Hz, 1H, H6-Q), 7.30 (d, J = 8.0 Hz, 1H, H8-Q),
7.34 (br s, 4H, H2/H6-Ar, H3/H5-Ar), 7.48 (ddd,
J = 8.0 Hz, J = 7.8 Hz, J = 1.0 Hz, 1H, H7-Q), 7.70 (dd,
J = 8.0 Hz, J = 1.0 Hz, 1H, H5-Q), 12.40 (s, 1H, NH1-
Q); 13C{1H} NMR (126 MHz, DMSO-d6): δ 38.3 (Cα),
115.4 (C8-Q), 123.3 (C6-Q), 128.3 (C3/C5-Ar), 128.3
(C5-Q), 128.8 (C4-Ar), 129.9 (C7-Q), 131.1 (C2/C6-Ar),
131.7 (C4a-Q), 132.0 (C8a-Q), 136.5 (C1-Ar), 154.5
(C3-Q), 160.0 (C2-Q); 15N NMR (51 MHz, DMSO-d6): δ
150.5 (N1-Q), 329.8 (N4-Q); IR (KBr, cmÀ1): ν 2965,
2837, 2713, 1662, 161 2, 1556, 1432, 1277, 1092, 1013,
917, 812, 758, 693; Anal. Calcd for (%) C15H11ClN2O:
C, 66.55; H, 4.10; N, 10.35. Found (%) C, 66.41; H,
4.06; N, 10.41.
mixtures of tautomers 10a–h/11a–h/12a–h.
Method B. A mixture of thiourea (0.10 g, 1.31 mmol)
and the corresponding quinoxalin-2(1H)-ones 9e–g
(1.19 mmol) in dry dioxane (10 mL) was heated at reflux
with stirring for 4 h. Gradually, a precipitate was formed,
which was filtered off and dried in air to afford
analytically pure samples of mixtures of tautomers 10e–g/
11e–g/12e–g.
3-(2,4-Dichlorobenzyl)quinoxalin-2(1H)-one (1f).
Beige
powder; 0.25 g, 73% yield (Method A); 0.43 g, 79%
1
yield (Method B); mp 247–249°С; H NMR (500 MHz,
DMSO-d6): δ 4.26 (s, 2H, CHα), 7.23 (ddd, J = 7.7 Hz,
J = 7.5 Hz, J = 1.1 Hz, 1H, H6-Q), 7.31 (dd, J = 7.7 Hz,
J = 1.1 Hz, 1H, H8-Q), 7.38 (dd, J = 8.1 Hz, J = 2.1 Hz,
1H, H5-Ar), 7.41 (d, J = 8.1 Hz, 1H, H6-Ar), 7.48 (ddd,
J = 7.7 Hz, J = 7.5 Hz, J = 1.1 Hz, 1H, H7-Q), 7.58 (dd,
J = 7.7 Hz, J = 1.1 Hz, 1H, H5-Q), 7.60 (d, J = 2.1 Hz,
1H, H3-Ar), 12.44 (s, 1H, NH1-Q); 13C{1H} NMR
(126 MHz, DMSO-d6): δ 36.0 (Cα), 115.3 (C8-Q), 123.1
(C6-Q), 127.1 (C5-Ar), 128.2 (C5-Q), 128.5 (C6-Ar),
129.8 (C7-Q), 131.5 (C4a-Q), 131.8 (C8a-Q), 131.9 (C4-
Ar), 133.1 (C3-Ar), 134.5 (C1-Ar), 134.7 (C2-Ar), 154.3
(Quinoxalin-2(1H)-on-2-yl)(phenyl)methyl
carbamimidothioate
(10a),
2′-imino-5′-phenyl-1H-
spiro[quinoxaline-2,4′-thiazolidin]-3(4H)-one (11a), and
2′-amino-5′-phenyl-1H,5′H-spiro[quinoxaline-2,4′-
thiazol]-3(4H)-one
(12a)
hydrochlorides
were
characterized as the mixture of tautomers in percentage
ratio 32:28:40, respectively. Bright yellow solid; 0.55 g,
88% yield (Method A); mp 173–175°C; 1H NMR
(500 MHz, DMSO-d6): δ 5.31 [s, 1H, СH5′ (11a)], 5.89
[s, 1H, СH5′ (12a)], 6.55–6.69 (m, 7H, Ar + Q), 6.73 [s,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2019
3-Benzylquinoxalin-2(1H)-ones
1H, СHα (10a)], 6.88–7.86 (m, 20H, Ar + Q), 9.21–12.70
(s, 12H, NH); 13C{1H} NMR (126 MHz, DMSO-d6): δ
50.8, 56.7, 59.4, 81.9, 84.3, 113.6, 113.8, 114.7, 115.6,
118.4, 119.2, 123.1, 123.3, 123.4, 123.7, 124.0, 128.1,
128.3, 2 × 128.5, 128.6, 2 × 128.9, 129.0, 129.4, 129.6,
129.7, 130.3, 130.8, 130.9, 131.0, 132.0, 132.3, 136.3,
152.8, 156.3, 159.7, 160.2, 167.8, 170.1, 170.8, 183.9;
IR (KBr, cmÀ1): ν 3059, 1655, 1613, 1505, 1419, 1387,
750, 697; Anal. Calcd for (%) C16H15ClN4OS: C, 55.41;
H, 4.36; N, 16.15; S, 9.25. Found (%) C16H14N4OS: C,
55.16; H, 4.45; N, 16.26; S, 9.08.
1656, 1613, 1506, 1490, 1420, 1234, 753; Anal. Calcd
for (%) C16H14ClFN4OS: C, 52.67; H, 3.87; N, 15.36; S,
8.79. Found (%) C17H13FN4OS: C, 52.41; H, 3.78; N,
15.50; S, 8.98.
(3-Nitrophenyl)(quinoxalin-2(1H)-on-2-yl)methyl
carbamimidothioate (10d), 5′-(3-nitrophenyl)-2′-imino-
1H-spiro[quinoxaline-2,4′-thiazolidin]-3(4H)-one (11d),
and
2′-amino-5′-(3-nitrophenyl)-1H,5′H-
(12d)
spiro[quinoxaline-2,4′-thiazol]-3(4H)-one
hydrochlorides were characterized as the mixture of
tautomers in percentage ratio 30:25:45, respectively.
Light-brown solid; 0.63 g, 91% yield (Method A); mp
(4-Fluorophenyl)(quinoxalin-2(1H)-on-2-yl)methyl
carbamimidothioate (10b), 5′-(4-fluorophenyl)-2′-imino-
1
170–172°C; H NMR (500 MHz, DMSO-d6): δ 5.51 [s,
1H-spiro[quinoxaline-2,4′-thiazolidin]-3(4H)-one (11b),
1H, СHα (11d)], 5.93 [s, 1H, СH5′ (12d)], 6.37–6.91 (m,
7H, Ar + Q), 6.91 [s, 1H, СH5′ (10d)], 7.37–8.43 (m,
17H, Ar + Q), 9.26–12.76 (s, 12H, NH); 13C{1H} NMR
(126 MHz, DMSO-d6): δ 50.0, 55.6, 58.3, 84.4, 113.5,
114.2, 114.8, 115.8, 118.7, 119.5, 123.1, 123.4, 123.6,
2 × 123.8, 123.9, 124.5, 128.6, 129.7, 129.8, 130.1,
130.2, 130.9, 131.3, 132.5, 133.8, 134.9, 135.1, 135.5,
136.2, 138.7, 147.1, 147.4, 147.7, 152.8, 155.4, 159.7,
160.4, 167.1, 183.9; IR (KBr, cmÀ1): ν 3073, 1647,
1614, 1530, 1351, 755, 730, 680; Anal. Calcd for (%)
C16H14ClN5O3S: C, 49.04; H, 3.60; N, 17.87; S, 8.18.
Found (%) C, 48.72; H, 3.48; N, 17.68; S, 8.39.
and
2′-amino-5′-(4-fluorophenyl)-1H,5′H-
(12b)
spiro[quinoxaline-2,4′-thiazol]-3(4H)-one
hydrochlorides were characterized as the mixture of
tautomers in percentage ratio 25:25:50, respectively.
Light brown solid; 0.56 g, 85% yield (Method A); mp
1
163–165°C; H NMR (500 MHz, DMSO-d6): δ 5.35 [s,
1H, СH5′ (11b)], 5.83 [s, 1H, СH5′ (12b)], 6.53–6.70
(m, 7H, Ar + Q), 6.75 [s, 1H, СHα (10b)], 6.86–7.84 (m,
17H, Ar + Q), 7.89–12.80 (s, 12H, NH); 13C{1H} NMR
(126 MHz, DMSO-d6): δ 50.2, 55.9, 58.6, 82.0, 84.2,
113.6, 113.9, 114.7, 115.0, 183.9, 170.8, 170.3, 167.7,
163.3, 163.2, 162.9, 161.4, 161.2, 160.9, 160.3, 159.8,
156.1, 152.8, 115.1, 115.2, 115.3, 115.5, 115.6, 115.7,
118.5, 119.3, 123.2, 2 × 123.5, 132.7, 123.8, 123.9,
127.2, 127.3, 128.3, 128.4, 128.5, 129.7, 130.3, 130.7,
2 × 130.8, 131.1, 2 × 131.2, 131.7, 131.8, 132.4, 132.6;
IR (KBr, cmÀ1): ν 3360, 3071, 1678, 1661, 1604, 1508,
1420, 1231, 752, 571; Anal. Calcd for (%)
C16H14ClFN4OS: C, 52.67; H, 3.87; N, 15.36; S, 8.79.
Found (%) C, 52.98; H, 3.74; N, 15.53; S, 8.95.
(4-Chlorophenyl)(quinoxalin-2(1H)-on-2-yl)methyl
carbamimidothioate (10e), 5′-(4-chlorophenyl)-2′-imino-
1H-spiro[quinoxaline-2,4′-thiazolidin]-3(4H)-one (11e),
and
2′-amino-5′-(4-chlorophenyl)-1H,5′H-
(12e)
spiro[quinoxaline-2,4′-thiazol]-3(4H)-one
hydrochlorides were characterized as the mixture of
tautomers in percentage ratio 35:25:40, respectively.
Beige solid; 0.60 g, 88% yield (Method A); 0.38 g, 82%
1
yield (Method B); mp 202–204°C; NMR data for 10e: H
(2-Fluorophenyl)(quinoxalin-2(1H)-on-2-yl)methyl
carbamimidothioate (10c), 5′-(2-fluorophenyl)-2′-imino-
1H-spiro[quinoxaline-2,4′-thiazolidin]-3(4H)-one (11c),
NMR (500 MHz, DMSO-d6): δ 6.76 (s, 1H, СHα), 7.36–
7.40 (m, 2H, H6-Q, H8-Q), 7.44 (d, J = 8.6 Hz, 2H,
H3/H5-Ar), 7.54 (d, J = 8.6 Hz, 2H, H2/H6-Ar), 7.59
(ddd, J = 7.8 Hz, J = 7.6 Hz, J = 0.9 Hz, 1H, H7-Q),
7.83 (dd, J = 7.8 Hz, J = 0.9 Hz, 1H, H5-Q), 12.74 (s,
1H, NH1-Q); 13C{1H} NMR (126 MHz, DMSO-d6): δ
50.2 (Cα), 115.7 (C8-Q), 123.6 (C6-Q), 128.5 (C5-Q),
128.7 (C3/C5-Ar), 130.3 (C3-Q), 130.4 (C2/C6-Ar),
130.7 (C4a-Q), 131.4 (C7-Q), 132.3 (C8a-Q), 133.4 (C4-
Ar), 135.5 (C1-Ar), 155.9 (C2-Q), 167.5 (H2N─C═NH);
15N NMR (51 MHz, DMSO-d6): δ 153.7 (N1-Q), 328.1
(N4-Q). The signals of H2N─C═NH, H2N─C═NH,
H2N─C═NH, and H2N─C═NH have not been observed.
and
2′-amino-5′-(2-fluorophenyl)-1H,5′H-
(12c)
spiro[quinoxaline-2,4′-thiazol]-3(4H)-one
hydrochlorides were characterized as the mixture of
tautomers in percentage ratio 31:28:41, respectively.
Bright yellow solid; 0.50 g, 77% yield (Method A); mp
1
165–167°C; H NMR (500 MHz, DMSO-d6): δ 5.35 [s,
1H, СH5′ (11c)], 5.92 [s, 1H, СH5′ (12c)], 6.40–6.69 (m,
7H, Ar + Q), 6.79 [s, 1H, СHα (10c)], 6.79–7.83 (m,
17H, Ar + Q), 8.79–12.80 (s, 12H, NH); 13C{1H} NMR
(126 MHz, DMSO-d6): δ 46.2, 48.6, 50.3, 52.0, 81.9,
84.3, 113.3, 114.3, 114.6, 114.9, 115.0, 115.1, 115.2,
115.3, 115.7, 115.9, 116.1, 118.5, 118.8, 119.5, 120.2,
2 × 123.2, 123.4, 2 × 123.5, 123.8, 124.3, 2 × 124.4,
2 × 124.5, 2 × 124.9, 128.6, 129.6, 2 × 129.9, 130.2,
130.6, 2 × 130.8, 131.0, 131.1, 131.2, 2 × 131.4, 132.5,
152.9, 155.2, 158.8, 159.3, 160.8, 161.0, 161.1, 161.2,
167.8, 170.0, 171.5, 183.9; IR (KBr, cmÀ1): ν 3064,
1
NMR data for 11e: H NMR (500 MHz, DMSO-d6): δ
5.31 (s, 1H, СH5′-Tz), 6.58 (d, J = 7.8 Hz, 1H, H8-Q),
6.66–6.68 (m, 1H, H5-Q), 6.68 (ddd, J = 7.8 Hz,
J = 7.6 Hz, J = 1.2 Hz, 1H, H6-Q), 6.88 (ddd,
J = 7.8 Hz, J = 7.6 Hz, J = 1.2 Hz, 1H, H7-Q), 7.16 (d,
J = 8.5 Hz, 2H, H2/H6-Ar), 7.30 (d, J = 8.5 Hz, 2H,
H3/H5-Ar), 7.92 (s, 1H, NH4-Q), 10.72 (s, 1H, NH1-Q);
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

V. A. Mamedov, N. A. Zhukova, V. V. Syakaev, T. N. Beschastnova, M. S. Kadyrova,
A. O. Isaeva, S. V. Mamedova, E. L. Gavrilova, S. K. Latypov, and O. G. Sinyashin
Vol 000
13C{1H} NMR (126 MHz, DMSO-d6): δ 58.5 (C5′-Tz),
84.2 (C4′-Tz, C3-Q), 114.1 (C6-Q), 114.7 (C8-Q), 119.5
(C5-Q), 123.4 (C7-Q), 123.9 (C8a-Q), 128.1 (C3/C5-Ar),
130.2 (C4a-Q, C1-Ar), 130.7 (C2/C6-Ar), 133.4 (C4-Ar),
159.6 (C2-Q), 170.7 (C2′-Tz); 15N NMR (51 MHz,
DMSO-d6): δ 134.2 (N1-Q), 78.3 (N4-Q). The signals of
NH3′-Tz, C═NH-Tz, NH3′-Tz, and C═NH-Tz have not
Beige solid; 0.68 g, 89% yield (Method A); 0.45 g, 89%
yield (Method B); mp 208–210°C; H NMR (500 MHz,
1
DMSO-d6): δ 5.24 [s, 1H, СH5′ (11g)], 5.85 [s, 1H,
СH5′ (12g)], 6.53–6.721 (m, 7H, Ar + Q), 6.72 [s, 1H,
СHα (10g)], 6.89–7.84 (m, 17H, Ar + Q), 7.85–12.72 (s,
12H, NH); 13C{1H} NMR (126 MHz, DMSO-d6): δ
50.3, 56.0, 58.6, 81.6, 84.3, 113.7, 114.0, 114.7, 114.8,
115.7, 118.6, 119.4, 121.7, 122.1, 122.3, 123.1, 123.5,
123.6, 123.7, 124.0, 128.5, 129.7, 129.8, 130.2, 130.7,
130.8, 131.0, 131.0, 131.1, 131.2, 131.5, 131.6, 131.8,
132.1, 132.4, 135.9, 152.8, 155.8, 159.5, 167.5, 170.4,
170.8; IR (KBr, cmÀ1): ν 3268, 2998, 2960, 2887, 1641,
1483, 1422, 1120, 873, 762, 716, 567; Anal. Calcd for
(%) C16H14BrClN4OS: C, 45.14; H, 3.31; N, 13.16; S,
7.53. Found (%) C, 45.28; H, 3.40; N, 13.21; S, 7.42.
(6,7-Dichloroquinoxalin-2(1H)-on-2-yl)(phenyl)methyl
carbamimidothioate (10h), 6,7-dichloro-2′-imino-5′-
phenyl-1H-spiro[quinoxaline-2,4′-thiazolidin]-3(4H)-one
1
been observed. NMR data for 12e: H NMR (500 MHz,
DMSO-d6): δ 5.85 (s, 1H, СH5′-Tz), 6.52–6.56 (m, 2H,
H6-Q, H7-Q), 6.70 (d, J = 7.6 Hz, 1H, H8-Q), 6.89–6.91
(m, 1H, H5-Q), 7.40 (d, J = 8.5 Hz, 2H, H2/H6-Ar), 7.31
(d, J = 8.5 Hz, 2H, H3/H5-Ar), 7.49 (s, 1H, NH4-Q),
11.14 (s, 1H, NH1-Q); 13C{1H} NMR (126 MHz,
DMSO-d6): δ 55.8 (C5′-Tz), 82.0 (C4′-Tz, C3-Q), 113.7
(C6-Q), 114.0 (C5-Q), 114.7 (C8-Q), 118.6 (C7-Q),
123.4 (C8a-Q), 128.3 (C3/C5-Ar), 129.7 (C4a-Q), 131.3
(C2/C6-Ar), 133.7 (C1-Ar), 133.9 (C4-Ar), 152.7 (C2′-
Tz), 160.2 (C2-Q); 15N NMR (51 MHz, DMSO-d6): δ
134.8 (N1-Q), 174.6 (N4-Q). The signals of NH2-Tz,
NH3′-Tz, and NH2-Tz have not been observed. IR (KBr,
cmÀ1): ν 3071, 1643, 1614, 1487, 1423, 1093, 758, 607,
567; Anal. Calcd for (%) C16H14Cl2N4OS: C, 50.40; H,
3.70; N, 14.69; S, 8.41. Found (%) C, 50.51; H, 3.76; N,
14.62; S, 8.31.
(11h),
and
2′-amino-6,7-dichloro-5′-phenyl-1H,5′H-
(12h)
spiro[quinoxaline-2,4′-thiazol]-3(4H)-one
hydrochlorides were characterized as the mixture of
tautomers in percentage ratio 3:35:62, respectively. Gray-
green solid; 0.56 g, 75% yield (Method A); mp 241–
1
243°C; H NMR (500 MHz, DMSO-d6): δ 5.41 [s, 1H,
(2,4-Dichlorophenyl)(quinoxalin-2(1H)-on-2-yl)methyl
carbamimidothioate (10f), 5′-(2,4-dichlorophenyl)-2′-
imino-1H-spiro[quinoxaline-2,4′-thiazolidin]-3(4H)-one
(11f), and 2′-amino-5′-(2,4-dichlorophenyl)-1H,5′H-
СH5′ (11h)], 5.82 [s, 1H, СH5′ (12h)], 6.65–6.67 (m,
2H, Q), 6.70 [s, 1H, СHα (10h)], 6.81–8.21 (m, 19H,
Ar + Q), 8.42–11.40 (s, 12H, NH); 13C{1H} NMR
(126 MHz, DMSO-d6): δ 48.6, 57.1, 59.4, 81.5, 83.7,
114.2, 114.5, 2 × 115.4, 119.2, 119.9, 123.9, 124.2,
124.3, 124.5, 125.0, 127.0, 128.3, 2 × 128.4, 2 × 129.0,
2 × 129.1, 2 × 129.2, 129.4, 2 × 129.6, 129.7, 130.2,
130.4, 130.8, 131.0, 131.4, 153.4, 157.7, 159.5, 160.3,
167.1, 170.5, 171.0; IR (KBr, cmÀ1): ν 3078, 3057,
1690, 1651, 1615, 1499, 1377, 1125, 698; Anal. Calcd
for (%) C16H13Cl3N4OS: C, 46.23; H, 3.15; N, 13.48; S,
7.71. Found (%) C, 46.10; H, 3.03; N, 13.57; S, 7.83.
spiro[quinoxaline-2,4′-thiazol]-3(4H)-one
(12f)
hydrochlorides were characterized as the mixture of
tautomers in percentage ratio 30:26:44, respectively.
Yellow solid; 0.60 g, 80% yield (Method A); 0.40 g,
80% yield (Method B); mp 160–162°C; 1H NMR
(500 MHz, DMSO-d6): δ 5.43 [s, 1H, CH5′ (11f)], 5.93
[s, 1H, CH5′ (12f)], 6.38–6.70 (m, 5H, Ar + Q), 6.73 [s,
1H, CHα (10f)], 6.87–7.98 (m, 16H, Ar + Q), 8.98–12.71
(s, 12H, NH); 13C{1H} NMR (126 MHz, DMSO-d6): δ
49.2, 52.5, 54.9, 81.6, 84.5, 113.2, 114.4, 114.6, 114.9,
115.7, 118.5, 119.4, 123.0, 123.4, 2 × 123.6, 124.3,
2 × 127.5, 128.0, 128.3, 128.4, 128.7, 128.9, 129.4,
129.6, 130.1, 130.2, 130.9, 2 × 131.0, 132.4, 132.5,
133.1, 133.4, 2 × 134.0, 2 × 134.2, 134.5, 134.7, 153.0,
155.0, 158.8, 161.2, 167.9, 170.1, 171.3; IR (KBr,
cmÀ1): ν 3064, 1653, 1614, 1588, 1505, 1472, 1383,
1103, 749; Anal. Calcd for (%) C16H13Cl3N4OS: C,
46.23; H, 3.15; N, 13.48; S, 7.71. Found (%) C, 46.51;
H, 3.01; N, 13.31; S, 7.50.
Reaction of quinoxalin-2(1H)-one 9h with thiourea in
dioxane.
(6,7-Dichloroquinoxalin-2(1H)-on-2-yl)
(phenyl)methyl carbamimidothioate (10h), 6,7-dichloro-
2′-imino-5′-phenyl-1H-spiro[quinoxaline-2,4′-
thiazolidin]-3(4H)-one (11h), and 2′-amino-6,7-dichloro-
5′-phenyl-1H,5′H-spiro[quinoxaline-2,4′-thiazol]-3(4H)-
one (12h) hydrochlorides were characterized as the
mixture of tautomers in percentage ratio 4:37:59,
respectively. A mixture of quinoxalin-2(1H)-one 9h
(0.40 g, 1.19 mmol) and thiourea (0.10 g, 1.31 mmol) in
dry dioxane (10 mL) was heated at reflux with stirring for
4 h and then was evaporated in vacuum to dryness, and
the residue was washed in boiling i-PrOH, and the
undissolved part of precipitate was filtered hot and dried
in air to afford analytically pure samples of the by-
product 13. The filtrate was evaporated in vacuum to 2/3
of volume. The precipitate was filtered off and dried in
air to afford analytically pure samples of the mixture of
(4-Bromophenyl)(quinoxalin-2(1H)-on-2-yl)methyl
carbamimidothioate (10g), 5′-(4-bromophenyl)-2′-imino-
1H-spiro[quinoxaline-2,4′-thiazolidin]-3(4H)-one (11g),
and
2′-amino-5′-(4-bromophenyl)-1H,5′H-
(12g)
spiro[quinoxaline-2,4′-thiazol]-3(4H)-one
hydrochlorides were characterized as the mixture of
tautomers in percentage ratio 31:31:38, respectively.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2019
3-Benzylquinoxalin-2(1H)-ones
tautomers 10h/11h/12h in a 71% yield, the characteristics
of which are similar to the characteristics of the mixture
of tautomers 10h/11h/12h, obtained by the method
described earlier.
The precipitate was filtered off and dried in air to afford
an analytically pure sample of compound 14a.
As
a
by-product,
7,8-dichloro-1-imino-3-
phenylthiazolo[3,4-a]quinoxalin-4(5H)-one (13) was
obtained as a yellow-green solid, 82.0 mg, 19% yield;
1
mp 323–325°C; H NMR (500 MHz, DMSO-d6): δ 7.26
(s, 1H, H6-TzQ), 7.38–7.42 (m, 3H, H4-Ar, H3/H5-Ar),
7.46–7.49 (m, 2H, H2/H6-Ar), 9.60 (s, 1H, H9-TzQ),
11.34 (s, 1H, NH5-TzQ); 13C{1H} NMR (126 MHz,
DMSO-d6): δ 115.5 (C6-TzQ), 118.8 (C9-TzQ), 120.3
(C3a-TzQ), 123.4 (C8-TzQ), 124.5 (C3-TzQ), 124.6
(C9a-TzQ), 126.1 (C7-TzQ), 127.9 (C3-Ar), 128.7 (C5a-
TzQ), 128.9 (C4-Ar), 130.0 (C2-Ar), 130.3 (C1-Ar),
153.5 (C4-TzQ), 158.4 (C1-TzQ); 15N NMR (51 MHz,
DMSO-d6): δ 135.5 (N5-TzQ), 144.7 (N10-TzQ). The
signal of NC(O)CH3 has not been observed. IR (KBr,
cmÀ1): ν 3332, 3028, 2926, 2854, 1686, 1619, 1600,
1479, 1401, 1200, 689, 617; Anal. Calcd for (%)
C16H9Cl2N3OS: C, 53.05; H, 2.50; N, 11.60; S, 8.85.
1-Acetylimino-7,8-dichloro-3-phenylthiazolo[3,4-a]
quinoxalin-4(5H)-one
(14a).
Yellow-green
solid;
100.7 mg, 83% yield (Method A); 99.9 mg, 95% yield
(Method B); mp >350°C; 1H NMR (500 MHz,
DMSO-d6): δ 2.36 [s, 3H, C(O)CH3], 7.37 (s, 1H, H6-
Q), 7.43–7.48 (m, 3H, H4-Ar, H2/H6-Ar), 7.53–7.56 (m,
2H, H3/H5-Ar), 10.24 (s, 1H, H9-TzQ), 11.53 (s, 1H,
NH5-TQ); 13C{1H} NMR (126 MHz, DMSO-d6): δ 26.8
[C(O)CH3], 116.1 (C6-TQ), 119.5 (C3a-TzQ), 122.5 (C9-
TzQ), 123.3 (C9a-TQ), 123.8 (C3-TzQ), 127.8 (C2/C6-
Ar), 128.5 (C5a-TzQ), 128.9 (C4-Ar), 130.0 (C3-Ar),
130.1 (C1-Ar), 131.2 (C7-TzQ), 131.4 (C8-TQ), 153.1
(C4-TzQ), 162.3 (C1-TQ), 179.6 [C(O)CH3]; IR (KBr,
cmÀ1): ν 3121, 3054, 2947, 1709, 1583, 1478, 1454,
1366, 1263, 1217, 995, 692, 574; Anal. Calcd for (%)
C18H11Cl2N3O2S: C, 53.48; H, 2.74; N, 10.39; S, 7.93.
Found (%) C, 52.85; H, 2.57; N, 11.71; S, 8.71.
Transformation of the tautomeric mixture 10h/11h/12h to the
6,7-dichloro-2′-imino-5′-phenyl-1H-spiro[quinoxaline-2,4′-
thiazolidin]-3(4H)-one hydrochloride (11h).
A mixture of
tautomers 10h/11h/12h (0.10 g, 0.26 mmol) in EtOH/HCl
(1.3:1, v/v) was heated at reflux with stirring for 5 h. The
reaction mixture was evaporated in vacuum to dryness to
afford analytically pure samples of compound 11h in
quantitative yield. Yellow-green powder; 0.10 g, quant.
Found (%) C, 53.34; H, 2.66; N, 10.49; S, 8.06.
1-Acetylimino-3-phenythiazolo[3,4-a]quinoxalin-4(5H)-one
(14b). Light-yellow solid; 91.6 mg, 91% yield; mp 343–
345°C (ref. [26] 341–343°C); 1H NMR (500 MHz,
DMSO-d6): δ 2.36 [s, 3H, C(O)CH3], 7.235 (ddd,
J = 8.0 Hz, J = 7.8 Hz, J = 1.1 Hz, 1H, H8-TzQ), 7.244
(d, J = 8.0 Hz, 1H, H6-TzQ), 7.35 (ddd, J = 8.0 Hz,
J = 7.8 Hz, J = 1.1 Hz, 1H, H7-TzQ), 7.42–7.47 (m, 3H,
H4-Ar, H3/H5-Ar), 7.53–7.57 (m, 2H, H2/H6-Ar), 9.93
(dd, J = 8.0 Hz, J = 1.1 Hz, 1H, H9-TQ), 11.36 (s, 1H,
NH5-TzQ); 13C{1H} NMR (126 MHz, DMSO-d6): δ
26.8 [C(O)CH3], 115.6 (C6-TzQ), 120.2 (C3a-TzQ),
121.2 (C9-TzQ), 122.2 (C8-TzQ), 124.3 (C9a-TzQ),
127.0 (C7-TzQ), 127.7 (C3/C5-Ar), 128.7 (C4-Ar), 129.0
(C5a-TzQ), 130.1 (C2/C6-Ar), 130.6 (C1-Ar), 130.7 (C3-
TzQ), 153.3 (C4-TzQ), 162.2 (C1-TzQ), 179.6 [C(O)
CH3]; 15N NMR (51 MHz, DMSO-d6): δ 135.0 (N5-
TzQ), 162.3 (N10-TzQ), 222.7 [NC(O)CH3]; IR (KBr,
cmÀ1): ν 3036, 2993, 2917, 1681, 1626, 1466, 1358,
1264, 1218, 762, 690, 660, 571; Anal. Calcd for (%)
1
yield; mp 218–220°C; H NMR (500 MHz, DMSO-d6): δ
5.81 (s, 1H, СH5′-Tz), 6.71 (s, 1H, H8-Q), 6.86 (s, 1H,
H5-Q), 7.22–7.28 (m, 3H, H4-Ar, H3/H5-Ar), 7.38–7.42
(m, 2H, H2/H6-Ar), 8.04 (s, 1H, NH1-Q), 9.85 (s, 1H,
NH3′-Tz), 10.41 (s, 1H, NH2′-Tz), 11.45 (s, 1H, NH4-
Q); 13C{1H} NMR (126 MHz, DMSO-d6): δ 57.0 (C5′-
Tz), 81.3 (C4′-Tz, C2-Q), 114.2 (C8-Q), 115.4 (C5-Q),
119.1 (C4a-Q), 124.0 (C6-Q), 124.3 (C7-Q), 128.4 (C3/
C5-Ar), 129.2 (C4-Ar), 129.6 (C2/C6-Ar), 130.3 (C8a-
Q), 130.5 (C1-Ar), 160.2 (C3-Q), 170.6 (C2′-Tz); 15N
NMR (51 MHz, DMSO-d6): δ 74.5 (N1-Q), 110.2 (NH3′-
Tz), 134.2 (N4-Q). The signal of C═NH-Tz has not been
observed. IR (KBr, cmÀ1): ν 3343, 3178, 3061, 1688,
1671, 1500, 1376, 1125, 872, 702, 595, 577; Anal. Calcd
for (%) C16H13Cl3N4OS: C, 46.23; H, 3.15; N, 13.48; S,
7.71. Found (%) C, 46.37; H, 3.24; N, 13.52; S, 7.59.
General procedures for the synthesis of 14a–f. Method
C18H13N3O2S: C, 64.46; H, 3.91; N, 12.53; S, 9.56.
Found (%) C, 64.34; H, 4.02; N, 12.40; S, 9.36.
A.
A
mixture of tautomers 10a–f/11a–f/12a–f
(0.30 mmol) in Ac2O (6 mL) was heated at reflux with
stirring for 1.5 h. The precipitate was filtered off and
dried in air to afford analytically pure samples of
compounds 14a–f.
Compound 11h (0.10 g, 0.26 mmol) in
Ac2O (6 mL) was heated at reflux with stirring for 1.5 h.
1-Acetylimino-3-(4-fluorophenyl)thiazolo[3,4-a]quinoxalin-
4(5H)-one (14c).
Pale yellow solid; 106.0 mg, quant.
1
yield; mp >350°C; H NMR (500 MHz, DMSO-d6): δ
2.36 [s, 3H, C(O)CH3], 7.22–7.26 (m, 2H, H6-TzQ, H8-
TzQ), 7.27 (dd, JHF = 9.9 Hz, JHH = 8.4 Hz, 2H, H3/H5-
Ar), 7.36 (ddd, J = 8.2 Hz, J = 8.0 Hz, J = 1.3 Hz, 1H,
Method B.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

V. A. Mamedov, N. A. Zhukova, V. V. Syakaev, T. N. Beschastnova, M. S. Kadyrova,
A. O. Isaeva, S. V. Mamedova, E. L. Gavrilova, S. K. Latypov, and O. G. Sinyashin
Vol 000
H7-TzQ), 7.61 (dd, JHF = 8.8 Hz, JHH = 8.4 Hz, 2H,
H2/H6-Ar), 9.93 (dd, J = 8.2 Hz, J = 1.3 Hz, 1H, H9-
TzQ), 11.38 (s, 1H, NH5-TzQ); 13C{1H} NMR
(126 MHz, DMSO-d6): δ 26.8 [C(O)CH3], 114.7 (d,
JCF = 22.0 Hz, C3-Ar), 115.6 (C8-TzQ), 120.5 (C3a-
TzQ), 121.2 (C9-TzQ), 121.5 (C3-TzQ), 122.3 (C6-TzQ),
124.3 (C9a-TzQ), 127.1 (C7-TzQ), 129.0 (C5a-TzQ),
129.5 (d, JCF = 2.7 Hz, C1-Ar), 132.3 (d, JCF = 9.3 Hz,
C2-Ar), 153.4 (C4-TzQ), 162.1 (C1-TzQ), 162.3 (d,
JCF = 246.3 Hz, C4-Ar), 179.6 [C(O)CH3]; IR (KBr,
cmÀ1): ν 3038, 2992, 2909, 1681, 1631, 1607, 1507,
1470, 1398, 1365, 1310, 1265, 1216, 833, 762, 603, 549,
512; Anal. Calcd for (%) C18H12FN3O2S: C, 61.18; H,
3.42; N, 11.89; S, 9.07. Found (%) C, 61.24; H, 3.35; N,
[C(O)CH3]; IR (KBr, cmÀ1): ν 3094, 2991, 1676, 1624,
1530, 1461, 1370, 1350, 1311, 1272, 1214, 751, 569;
Anal. Calcd for (%) C18H12N4O4S: C, 56.84; H, 3.18; N,
14.73; S, 8.43. Found (%) C, 56.78; H, 3.14; N, 14.79; S,
8.50.
1-Acetylimino-3-(4-chlorophenyl)thiazolo[3,4-a]quinoxalin-
4(5H)-one (14f).
Light-yellow solid; 103.0 mg, 93%
1
yield; mp >350°C; H NMR (500 MHz, DMSO-d6): δ
2.37 [s, 3H, C(O)CH3], 7.25 (ddd, J = 8.0 Hz,
J = 7.8 Hz, J = 1.1 Hz, 1H, H8-TzQ), 7.26 (d,
J = 8.0 Hz, 1H, H6-TzQ), 7.36 (ddd, J = 8.0 Hz,
J = 7.8 Hz, J = 1.1 Hz, 1H, H7-TzQ), 7.50 (d,
J = 8.6 Hz, 1H, H2/H6-Ar), 7.58 (d, J = 8.6 Hz, 1H,
H3/H5-Ar), 9.93 (dd, J = 8.0 Hz, J = 1.1 Hz, 1H, H9-
TzQ), 11.41 (s, 1H, NH5-TzQ); 13C{1H} NMR
(126 MHz, DMSO-d6): δ 26.8 [C(O)CH3], 115.7 (C6-
TzQ), 120.8 (C3a-TzQ), 121.1 (C9-TzQ), 122.3 (C8-
TzQ), 124.3 (C9a-TzQ), 127.1 (C7-TzQ), 127.7 (C2/C6-
Ar), 129.0 (C5a-TzQ), 129.1 (C4-Ar), 129.5 (C3-TzQ),
131.9 (C3/C5-Ar), 133.6 (C1-Ar), 153.3 (C4-TzQ), 162.2
(C1-TzQ), 179.6 [C(O)CH3]; 15N NMR (51 MHz,
DMSO-d6): δ 135.6 (N5-TzQ), 162.7 (br, N10-TzQ),
223.3 [NC(O)CH3]; IR (KBr, cmÀ1): ν 3045, 2992, 2910,
1671, 1624, 1461, 1396, 1363, 1266, 1215, 1089, 989,
825, 749, 586; Anal. Calcd for (%) C18H12ClN3O2S: C,
58.46; H, 3.27; N, 11.36; S, 8.67. Found (%) C, 58.68;
H, 3.37; N, 11.51; S, 8.55.
11.80; S, 9.18.
1-Acetylimino-3-(2-fluorophenyl)thiazolo[3,4-a]quinoxalin-
4(5H)-one (14d). Yellowish solid; 106.0 mg, quant. yield;
1
mp >350°C; H NMR (500 MHz, DMSO-d6): δ 2.38 [s,
3H, C(O)CH3], 7.21–7.31 (m, 4H, H6-TzQ, H8-TzQ,
H5-Ar, H4-Ar), 7.36 (ddd, J = 7.9 Hz, J = 7.7 Hz,
J = 1.3 Hz, 1H, H7-TzQ), 7.48–7.55 (m, 2H, H6-Ar, H3-
Ar), 9.94 (dd, J = 7.9 Hz, J = 1.3 Hz, 1H, H9-TzQ),
11.44 (s, 1H, NH5-TzQ); 13C{1H} NMR (126 MHz,
DMSO-d6): δ 26.8 [C(O)CH3], 115.3 (d, JCF = 21.7 Hz,
C4-Ar), 115.8 (C6-TzQ), 118.6 (d, JCF = 15.2 Hz, C1-
Ar), 121.9 (C9-TzQ), 122.1 (C3a-TzQ), 122.4 (C8-TzQ),
123.0 (C3-TzQ), 123.3 (d, JCF = 3.3 Hz, C5-Ar), 124.2
(C9a-TzQ), 129.0 (C5a-TzQ), 129.7 (C7-TzQ), 131.1 (d,
JCF = 8.3 Hz, C6-Ar), 131.8 (d, JCF = 1.7 Hz, C3-Ar),
152.9 (C4-TzQ), 159.3 (d, JCF = 247.9 Hz, C2-Ar), 162.6
(C1-TzQ), 179.7 [C(O)CH3]; 15N NMR (51 MHz,
DMSO-d6): δ 135.1 (N5-TzQ), 162.1 (N10-TzQ), 223.4
[NC(O)CH3]; IR (KBr, cmÀ1): ν 3051, 2915, 1681, 1624,
165, 1467, 1370, 1310, 1264, 1226, 762, 579, 461; Anal.
Calcd for (%) C18H12FN3O2S: C, 61.18; H, 3.42; N,
11.89; S, 9.07. Found (%) C, 61.29; H, 3.50; N, 11.84; S,
1-Acetylimino-3-(2,4-dichlorophenyl)thiazolo[3,4-a]
quinoxalin-4(5H)-one
(14g).
Yellow-brown solid;
118.9 mg, 98% yield; mp 294–296°C; 1H NMR
(500 MHz, DMSO-d6): δ 2.38 [s, 3H, C(O)CH3], 7.265
(d, J = 7.8 Hz, 1H, H6-TzQ), 7.267 (ddd, J = 7.8 Hz,
J = 7.6 Hz, J = 1.2 Hz, 1H, H8-TzQ), 7.37 (ddd,
J = 7.8 Hz, J = 7.6 Hz, J = 1.2 Hz, 1H, H7-TzQ), 7.51
(dd, J = 8.2 Hz, J = 2.0 Hz, 1H, H5-Ar), 7.55 (d,
J = 8.2 Hz, 1H, H6-Ar), 7.73 (d, J = 2.0 Hz, 1H, H3-Ar),
9.94 (dd, J = 7.8 Hz, J = 1.2 Hz, 1H, H9-TzQ), 11.47 (s,
1H, NH5-TzQ); 13C{1H} NMR (126 MHz, DMSO-d6): δ
26.8 [C(O)CH3], 115.8 (C6-TzQ), 120.9 (C9-TzQ), 122.5
(C8-TzQ), 122.6 (C9a-TzQ), 124.1 (C3a-TzQ), 125.3
(C3-TzQ), 126.9 (C5-Ar), 127.2 (C7-TzQ), 128.6 (C3-
Ar), 128.9 (C5a-TzQ), 129.1 (C1-Ar), 133.1 (C6-Ar),
134.2 (C4-Ar), 134.3 (C2-Ar), 152.8 (C4-TzQ), 162.5
(C1-TzQ), 179.7 [C(O)CH3]; IR (KBr, cmÀ1): ν 3054,
2991, 2913, 1681, 1614, 1581, 1461, 1373, 1278, 1224,
833, 757, 587; Anal. Calcd for (%) C18H11Cl2N3O2S: C,
53.48; H, 2.74; N, 10.39; S, 7.93. Found (%) C, 53.30;
H, 2.81; N, 10.50; S, 7.78.
8.95.
1-Acetylimino-3-(3-nitrophenyl)thiazolo[3,4-a]quinoxalin-
4(5H)-one (14e). Yellow solid; 103.8 mg, 91% yield; mp
1
346–348°C; H NMR (500 MHz, DMSO-d6): δ 2.38 [s,
3H, C(O)CH3], 7.27 (d, J = 8.0 Hz, 1H, H6-TzQ), 7.28
(ddd, J = 8.0 Hz, J = 7.8 Hz, J = 1.1 Hz, 1H, H8-TzQ),
7.38 (ddd, J = 8.0 Hz, J = 7.8 Hz, J = 1.1 Hz, 1H, H7-
TzQ), 7.75 (dd, J = 8.1 Hz, J = 8.1 Hz, 1H, H5-Ar), 8.00
(br d, J = 8.1 Hz, 1H, H6-Ar), 8.30 (dd, J = 8.1 Hz,
J = 1.9 Hz, 1H, H4-Ar), 8.41 (dd, J = 1.9 Hz,
J = 1.9 Hz, 1H, H2-Ar), 9.56 (dd, J = 8.0 Hz,
J = 1.1 Hz, 1H, H9-TzQ), 11.56 (s, 1H, NH5-TzQ);
13C{1H} NMR (126 MHz, DMSO-d6): δ 27.0 [C(O)
CH3], 115.9 (C6-TzQ), 121.2 (C9-TzQ), 121.9 (C3a-
TzQ), 122.6 (C8-TzQ), 123.5 (C4-Ar), 124.4 (C9a-TzQ),
125.2 (C2-Ar), 127.4 (C7-TzQ, C3-TzQ), 129.1 (C5a-
TzQ), 129.4 (C5-Ar), 132.1 (C1-Ar), 136.6 (C6-Ar),
147.1 (C3-Ar), 153.5 (C4-TzQ), 162.3 (C1-TzQ), 179.9
1-Acetylimino-3-(4-bromophenyl)thiazolo[3,4-a]quinoxalin-
4(5H)-one (14h).
Light-yellow solid; 111.9 mg, 90%
1
yield; mp 333–335°C; H NMR (500 MHz, DMSO-d6): δ
2.36 [C(O)CH3], 7.24–7.28 (m, 2H, H8-TQ, H6-TzQ),
7.35 (ddd, J = 8.0 Hz, J = 7.8 Hz, J = 1.3 Hz, 1H, H7-
TzQ), 7.50 (d, J = 8.5 Hz, 1H, H3/H5-Ar), 7.64 (d,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2019
3-Benzylquinoxalin-2(1H)-ones
[7] Wagle, S.; Adhikari, A. V.; Kumari, N. S. Indian J Chem
2008, 47B, 439.
J = 8.5 Hz, 1H, H2/H6-Ar), 9.92 (dd, J = 8.5 Hz,
J = 1.3 Hz, 1H, H9-TzQ), 11.41 (s, 1H, NH5-TzQ);
13C{1H} NMR (126 MHz, DMSO-d6): δ 26.8 [C(O)
CH3], 115.7 (C8-TzQ), 120.7 (C3a-TzQ), 121.1 (C9-
TzQ), 122.3 (C4-Ar, C6-TzQ), 124.3 (C9a-TzQ), 127.1
(C7-TzQ), 129.0 (C5a-TzQ), 129.1 (C1-Ar), 129.9 (C3-
TzQ), 130.7 (C2/C6-Ar), 132.1 (C3/C5-Ar), 153.3 (C4-
TzQ), 162.1 (C1-TzQ), 179.6 [C(O)CH3]; 15N NMR
(51 MHz, DMSO-d6): δ 135.5 (N5-TzQ), 162.6 (N10-
TzQ), 222.6 [NC(O)CH3]; IR (KBr, cmÀ1): ν 3042, 2989,
2900, 1670, 1605, 1459, 1392, 1362, 1265, 1215, 987,
822, 760, 748, 582; Anal. Calcd for (%) C18H12BrN3O2S:
C, 52.19; H, 2.92; N, 10.14; S, 7.74. Found (%) C,
52.30; H, 2.84; N, 10.19; S, 7.84.
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Acknowledgments. This work was partially supported by the
Russian Science Foundation (grant no. 14-23-00073-p). The
authors gratefully acknowledge the CSF-SAC FRC KSC RAS
for the registration of IR and NMR spectra.
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CONFLICT OF INTEREST
[19] Sigma-Aldrich online catalog.
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The authors confirm that this article content has no
conflict of interest.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

V. A. Mamedov, N. A. Zhukova, V. V. Syakaev, T. N. Beschastnova, M. S. Kadyrova,
A. O. Isaeva, S. V. Mamedova, E. L. Gavrilova, S. K. Latypov, and O. G. Sinyashin
Vol 000
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SUPPORTING INFORMATION
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Additional supporting information may be found online
in the Supporting Information section at the end of the
article.
Latypov, S. Magn Reson Chem 2005, 43, 816; (b) Mamedov, V.
A.; Zhukova, N. A.; Balandina, A. A.; Kharlamov, S. V.;
Beschastnova, T. N.; Rizvanov, I. K.; Latypov, S. K. Tetrahedron
2012, 68, 7363.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet