Fused polycyclic nitrogen-containing heterocycles: VII. Reaction products of 3-(α-chlorobenzyl)-1,2-dihydro-quinoxalin-2-one and thioureas as key intermediate compounds in the synthesis of thiazolo[3,4-a]quinoxalines

Article abstract of DOI:10.1023/B:RUJO.0000036075.88285.3f

Products of the reactions of 3-(α-chlorobenzyl)-1,2- dihydroquinoxalin-2-one with thiourea, N-phenylthiourea, N,N'-diphenylthiourea, 2-sulfanylbenzimidazole, 2-sulfanylbenzothiazole, and potassium thiocyanate were brought into intramolecular cyclizations. Specific features of these reactions are discussed.

Full text of DOI:10.1023/B:RUJO.0000036075.88285.3f

Russian Journal of Organic Chemistry, Vol. 40, No. 4, 2004, pp. 527–533. Translated from Zhurnal Organicheskoi Khimii, Vol. 40, No. 4, 2004,
pp. 557–563.
Original Russian Text Copyright © 2004 by Kalinin, Mamedov, Rizvanov, Levin.
Fused Polycyclic Nitrogen-Containing Heterocycles:
VII.* Reaction Products of 3-(α-Chlorobenzyl)-1,2-dihydro-
quinoxalin-2-one and Thioureas as Key Intermediate Compounds
in the Synthesis of Thiazolo[3,4-a]quinoxalines
A. A. Kalinin, V. A. Mamedov, I. Kh. Rizvanov, and Ya. A. Levin
Arbuzov Institute of Organic and Physical Chemistry, Kazan Research Center, Russian Academy of Sciences,
ul. Arbuzova 8, Kazan, 420088 Tatarstan, Russia
e-mail: mamedov@iopc.kcn.ru
Received May 6, 2002
Abstract—Products of the reactions of 3-(α-chlorobenzyl)-1,2-dihydroquinoxalin-2-one with thiourea,
N-phenylthiourea, N,N'-diphenylthiourea, 2-sulfanylbenzimidazole, 2-sulfanylbenzothiazole, and potassium
thiocyanate were brought into intramolecular cyclizations. Specific features of these reactions are discussed.
In the recent years, azolo[a]quinoxalines attract
persistent interest. However, these compounds remain
so far poorly studied despite the fact that a number of
their derivatives exhibit various practically important
properties, specifically pronounced biological activity
[2]. Introduction into the fused ring system of hetero-
atoms other than nitrogen, e.g., sulfur, was expected
to afford new azolo[a]quinoxaline analogs, thiazolo-
[a(or b)]quinoxalines, which could possess different
chemical properties and physiological activity. Unlike
thiazolo[b]quinoxalines (methods of synthesis and pro-
perties of which have been studied in sufficient detail),
relatively limited published data are available on
thiazolo[a]quinoxalines. Among the latter, mesoionic
thiazolo[3,2-a]quinoxalines are known; they were
obtained by intramolecular cyclization of 2-carboxy-
methylsulfanylquinoxalines [3, 4]. Thiazolo[3,4-a]-
quinoxalines were synthesized mainly via intramole-
cular condensation of complex and difficultly acces-
sible thiazole and tetrahydrothiazole derivatives [5–7].
We recently described a new efficient proedure for the
synthesis of thiazolo[3,4-a]quinoxalin-2-ones by reac-
tion of 3-(α-chlorobenzyl)-1,2-dihydroquinoxalin-2-
one (I) with potassium thiocyanate and N,N'-di-
phenylthiourea and subsequent cyclization of 3-(α-
thiocyanato)- and 3 [α-(N,N'-diphenylisothioureido)-
benzyl]quinoxalin-2-ones II and III. The cyclization
involves nucleophilic attack by the N4 atom on the
electrophilic carbon atom of the thiocyanato or iso-
thioureido group with formation of 1-imino (IV) and
1-phenylimino derivatives (V) [8] (Scheme 1).
Scheme 1.
R'N
S
Ph
O
N
N
Ph
SR
N
H
N
H
O
II, III
IV, V
II, R = CN; III, R = C(=NPh)NHPh; IV, R' = H; V, R' = Ph.
In continuation of these studies, the present article
reports on the behavior of 3-(α-chlorobenzyl)-1,2-di-
hydroquinoxalin-2-one (I) with various reagents which
are synthetic equivalents of the –N=C+–S– species, in
particular with thiourea, N-phenylthiourea, 2-sulfanyl-
benzimidazole, and 2-sulfanylbenzothiazole. The reac-
tions of compound I with thiourea, 2-sulfanylbenz-
imidazole, and 2-sulfanylbenzothiazole in DMSO at
room temperature afforded the corresponding 3-(α-RS-
benzyl)-2-oxo-1,2-dihydroquinoxaline hydrochlorides
which were treated with a solution of sodium car-
bonate to obtain free bases (Scheme 2). The structure
of products VI–VIII is confirmed by the upfield shift
1
of the benzylic proton signal in the H NMR spectrum
of VI (δ 6.0 ppm) and downfield shift of the same
* For communication VI, see [1].
1070-4280/04/4004-0527 © 2004 MAIK “Nauka/Interperiodica”

KALININ et al.
528
Scheme 2.
Ph
NH
N
H2NC(S)NH2
S
NH2
Ph
O
N
H
O
N
Cl
VI
N
Ph
N
H
SH
X
N
N
S
I
X
N
H
O
VII, VIII
VII, X = NH; VIII, R = S.
proton signal in the spectra of VII and VIII (δ 6.64
and 6.87 ppm, respectively) relative to the correspond-
ing signal of quinoxaline I (δ 6.53 ppm), as well as by
the data of elemental analysis (see Experimental).
isothioureide and isodithiocarbamate moieties both
which are parts of aromatic systems.
All known methods for the preparation of thiazolo-
[3,4-a]quinoxalines are based on either thiazole deriva-
tives [5, 9, 10] or, as we showed in [7, 8], quinoxaline
derivatives. Retrosynthetic analysis of the structure of
thiazolo[3,4-a]quinoxalines suggests that such systems
could be built up not only through synthon A [whose
synthetic equivalents are thiocyanato (II) and isothio-
ureido derivatives III and VI] but also from synthons
B1 and B2 using compound I and the corresponding
thiourea derivatives (Scheme 6) as equivalents. In fact,
by heating thiourea, N-phenylthiourea, or N,N'-di-
phenylthiourea with quinoxaline I in dioxane with
subsequent addition of acetic anhydride we obtained
thiazoloquinoxalines V and IX (Scheme 7). This reac-
tion may be regarded as a one-pot procedure for the
synthesis of such compounds. It should be noted that,
like unsubstituted thiourea, N-phenylthiourea reacts
with quinoxaline VI to give acetylimino rather than
phenylimino derivative, i.e., elimination of aniline
rather than acetamide occurs.
Compounds VI–VIII turned out to be stable under
the conditions ensuring intramolecular cyclization of
thiocyanate II and diphenylisothioureide III to thia-
zoloquinoxalines, i.e., on heating in 10% hydrochloric
acid or in acetic acid [8]. We succeeded in obtaining
1-acetyliminothiazolo[3,4-a]quinoxaline IX in a poor
yield only by prolonged (~25 h) heating of quinoxaline
VI in boiling acetic acid (Scheme 3). Replacement of
acetic acid by acetic anhydride allowed us not only to
strongly shorten the reaction time (to one minute) but
also to raise the yield of compound IX to almost
quantitative.
Scheme 3.
AcN
S
N
Ph
AcOH, Ac2O
VI
However, the yield of thiazolo[3,4-a]quinoxaline
IX is considerably lower than in the two-step synthesis
through isothioureide VI, presumably due to side
processes. Heating of quinoxaline I with thiourea over
a period of 4 h gave in a good yield a crystalline
substance. The high-resolution mass spectrum of the
product contained the molecular ion peak with
m/z 236.094 (Irel 100%) which corresponded to the
elemental composition C15H12N2O (Mcalc 236.095). In
addition, in the mass spectra of the same sample,
obtained at lower temperature of the direct inlet probe,
we observed peaks belonging to molecular sulfur (S8).
We failed to obtain an analytically pure sample even
N
H
O
IX
Presumably, the cyclization of VI to IX is preceded
by acetylation with formation of intermediate mono-
(VIa) and/or diacetylisothioureide (VIb) having
readily departing AcNH groups (Scheme 4). Unlike
compounds VI, no cyclization of VII and VIII
occurred in boiling acetic anhydride. Here, compound
VII was acetylated to give the corresponding N-acetyl
derivative XII (Scheme 5). The lack of intramolecular
cyclization is likely to result from the nature of the
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 4 2004

FUSED POLYCYCLIC NITROGEN-CONTAINING HETEROCYCLES: VII.
529
Scheme 4.
H2N
Ac2N
S
Ph
O
NAc
NHAc
Ph
O
NH
N
N
Ph
S
S
NAc2
2Ac2O
VI
–2AcOH
N
H
N
H
N
O
H
VIb
VIb
Ac2O
N
–AcOH
H2N
AcHN
S
Ph
S
NAc
NH2
N
Ph
Ac2O
Ac2O
III
IX
–AcNH2
–AcOH
–AcOH
N
H
O
N
H
O
VIa
AcHN
AcHN
S
N
Ph
H+
VIb
IX
–AcNH2
–H+
N
H
O
by repeated crystallizations from dioxane, although
the H NMR spectra were identical, regardless of the
initial intramolecular nucleophilic condensation with
participation of one exocyclic and one endocyclic
imino group in hydrochloride VI in a way similar to
the condensation of the imino group and γ-carbonyl
group in compounds having an N–C–S–C–C fragment
[11, 12]. By analogy with six-membered sulfur-con-
taining systems [13, 14], acid-catalyzed isomerization
1
number of recrystallizations. The spectra contained
singlets at δ 4.39 (2H) and 12.45 ppm (1H) from the
CH2 and NH protons, respectively, and a multiplet at
δ 7.19–7.77 ppm from 9 aromatic protons. These data
confirm the formation of 3-benzyl-1,2-dihydroquino-
xalin-2-one (XIII) as the major product (Scheme 8).
Scheme 6.
The formation of compound XIII may be
rationalized in terms of a reaction sequence including
RN
RN
S
S
N
N
Ph
Ph
Scheme 5.
II, III, VI
Ph
N
N
H
O
N
H
O
S
N
Ac2O
S
VII
A
N
N
O
RHN
Ac
H
RN
C
XII
S
R'HN
B1
RN
S
X
Ac2O
S
N
N
Ph
HN
VII, VIII
Ph
I
N
Ph
N
H
O
N
O
H
N
H
O
B2
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 4 2004

KALININ et al.
530
Scheme 7.
zolylimino)thiazolo[3,4-a]quinoxaline XV (Scheme 11).
RN
The electron impact mass spectrum of XV contained
the molecular ion peak with m/z 528 (Irel 30%). The
precise m/z value (528.091) corresponds to the formula
C27H20N4O4S2 (Mcalc 528.093). The presence of a thia-
zoloquinoxaline fragment gives rise to the following
characteristic fragment ions, m/z (Irel, %): 293 (42),
266 (100), 236 (68), 235 (39), 234 (40), 206 (26), 205
(31). The fragment ions with m/z 237 (11) and 121 (67)
are formed by decomposition of the thiazole ring
[6, 7]. In the near-molecular region of the spectrum,
ion peaks with m/z 510 (25) and 452 (55) were present.
The first of these results from elimination of water
molecule from the molecular ion, indicating the pres-
ence of a hydroxy group, and the second corresponds
to expulsion of C2H2O2 from the ion with m/z 510.
A number of abundant ions in the mass spectrum of
XV appear due to localization of the positive charge on
both thiazolo[3,4-a]quinoxaline fragment and that
containing the thiazole ring (originally located at
position 1 of the tricyclic system). Thus the thiazolo-
[3,4-a]quinoxaline fragment gives rise to the following
fragment ions, m/z (Irel, %): 293 (42), 266 (100), 236
(68), 235 (39), 234 (40), 206 (26), 205(31); the ion
peak with m/z 237 (11) belongs to the thiazole ring
[15, 16]. An important information can be deduced
from the presence of an ion peak with m/z 320 (33).
The elemental composition of this ion is C17H10N3O2S;
it includes the thiazolo[3,4-a]quinoxaline ring system,
imino nitrogen atom, and C2–OH fragment of the
thiazole ring. Therefore, the product has structure XV
rather than isomeric structure XVI or XVII.
H2NC(S)NH2
S
or H2NC(S)NHPh
or PhNHC(S)NHPh
dioxane, Ac2O
N
Ph
I
N
H
O
V, IX
V, R = Ph; IX, R = Ac.
Scheme 8.
N
H2NC(S)NH2
Ph
I
N
H
O
XIII
of the spiro-fused thiazolidine system leads to bicyclic
structure which loses sulfur atom to give less stable
azetine system. The latter is stabilized via elimina-
tion of cyanamide as shown in Scheme 9.
Retrosynthetic analysis shows that not only thiazole
[5, 9, 10] or quinoxaline derivatives [7, 8] may be
precursors of thiazolo[3,4-a]quinoxalines. These com-
pounds can be built up from structures containing no
such heterocyclic systems, e.g., from synthons C, D,
and E whose synthetic equivalents are methyl chloro-
(phenyl)pyruvate (XIV), potassium thiocyanate
(KSCN), and o-phenylenediamine, respectively
(Scheme 10). The reaction of chloropyruvate XIV with
potassium thiocyanate gave a tarry material, treatment
of which with o-phenylenediamine afforded 1-(2-thia-
Scheme 9.
H
Ph
Ph
O
NH2
NH
Ph
S
S
NH2
H
H
N
N
N
NH
S
NH
I
·HCl
·HCl
·HCl
N
H
O
N
H
N
H
N
H
O
Ph
Ph
O
H
NH2
N
N
NH2
N
O
·HCl
·HCl
–S
H
NH2
N
H
N
H
Ph
O
N
NH
·HCl
XIII·HCl
XIII
–H2NCN
NH2
N
H
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 4 2004

FUSED POLYCYCLIC NITROGEN-CONTAINING HETEROCYCLES: VII.
531
Scheme 10.
mixing of the reactants (KSCN + o-phenylenediamine
+ XIV or o-phenylenediamine + XIV + KSCN),
thiazolo[3,4 a]quinoxaline system is formed. In both
cases, from the reaction mixture we isolated a small
amount of 1-acetylimino derivative IX rather than
thiazolylimino derivative XV. However, this approach
to thiazoloquinoxalines requires further study which
will be the subject of our subsequent publications.
Cl
O
R3
C
C
C
O
Ph
OMe
O
C
XIV
R1
N
R2
S
R3
EXPERIMENTAL
KSCN
S
C
R4
The melting points were determined on a Boetius
device. The IR spectra were recorded on a UR-20
spectrometer from samples dispersed in mineral oil.
N
D
N 2–
N 2–
NH2
NH2
1
The H NMR spectra were measured on a Bruker-250
spectrometer (250.13 MHz). The electron impact mass
spectra (70 eV) were obtained on an MKh-1310
instrument at a resolution R of 1500; electron collector
current 30–60 µA; vaporizer temperature 80–200°C;
SVP-5 direct inlet probe.
E
Scheme 11.
H
N
MeOCO
OH
3-Phenyl-1-phenylimino-4,5-dihydrothiazolo-
[3,4-a]quinoxalin-4-one (V). a. A solution of 0.30 g
of quinoxaline I and 0.27 g of N,N'-diphenylthiourea in
5 ml of dioxane was heated for 0.5 h under reflux, 2 ml
of acetic anhydride and 2 ml of acetic acid were added,
and the mixture was refluxed for 0.5 h, cooled, and
poured into water. The solution was separated from the
tarry material, 10 ml of 2-propanol was added, and the
mixture was heated to the boiling point. After cooling,
the precipitate was filtered off and washed with
an aqueous solution of sodium carbonate, water, and
2-propanol. Yield 41 mg (10%).
N
S
(1) KSCN
(2) o-C6H4(NH2)2
S
Ph
N
Ph
XIV
N
H
O
XV
HO
N
S
MeOCO
N
S
Ph
H
N
Ph
b. A solution of 1.00 g of quinoxaline I and 0.92 g
of N,N'-diphenylthiourea in 20 ml of dioxane was
heated for 25 h under reflux. The mixture was cooled
and poured into water. The tarry material was
separated from the solution, 10 ml of 2-propanol was
added, and the mixture was heated to the boiling point.
After cooling, the precipitate was filtered off and
washed with a solution of sodium cabonate, water, and
2-propanol. Yield 50 mg (12%). The physical constants
of samples of V prepared by the two methods were
identical to those reported in [7].
N
H
O
XVI
MeOCO
Ph
N
S
OH
NH
N
S
Ph
N
H
O
XVII
3-(α-Isothioureidobenzyl)-1,2-dihydroquino-
xalin-2-one (VI). A solution of 2.00 g of compound I
and 0.62 g of thiourea in 20 ml of DMSO was stirred
for 6 h, and the mixture was left overnight. It was
then poured into water and made alkaline by adding
a 5% aqueous solution of sodium carbonate. The
product was filtered off and washed with water. Yield
The formation of thiazolo[3,4-a]quinoxaline system
is also confirmed by the presence of a doublet signal
from 9-H (J = 8.5 Hz), which is typical of such
systems [8, 17, 18]: this proton resonates separately
from the other 13 aromatic protons, in a weaker field.
It should be noted that, regardless of the order of
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 4 2004

KALININ et al.
532
2.11 g (92%), mp 207–208°C. IR spectrum, ν, cm–1:
was filtered off and washed with 2-propanol. Yield
1.08 g (95%).
1620 (C=N); 1680 (C=O); 2300–3220 (NH, car-
1
bamoyl); 3380, 3440 (NH, NH2). H NMR spectrum
c. A solution of 0.30 g of quinoxaline V and 0.09 g
of thiourea in 5 ml of dioxane was heated for 0.5 h
under reflux, 2 ml of acetic anhydride and 2 ml of
acetic acid were added, and the mixture was refluxed
for 0.5 h. It was then cooled, and the precipitate was
filtered off, washed with a solution of sodium carbo-
nate, water, and 2-propanol. Yield 0.11 g (35%).
d. A solution of 0.3 g of quinoxaline V and 0.16 g
of N-phenylthiourea in 5 ml of dioxane was heated
for 0.5 h under reflux, 2 ml of acetic anhydride and
2 ml of acetic acid were added, and the mixture was
refluxed for 0.5 h. It was then cooled, and the precip-
itate was filtered off, washed with a solution of sodium
carbonate, water, and 2-propanol. Yield 32 mg (10%).
e. A solution of 0.9 g of compound XV in 5 ml
of acetic acid was added to a mixture of 0.41 g of
potassium thiocyanate, 0.45 g of o-phenylenediamine
and 10 ml of acetic acid. The mixture was heated for
2 h under reflux and left overnight. The precipitate
was filtered off and washed with 2-propanol. Yield
0.11 g (8%).
f. A solution of 0.7 g of chloropyruvate XIV in 5 ml
of acetic acid was added to a mixture of 0.35 g of
o-phenylenediamine and 10 ml of acetic acid, and,
after 15 min, 0.32 g of potassium thiocyanate was
added. The mixture was heated for 2 h under reflux
and left overnight. The precipitate was filtered off and
washed with 2-propanol. Yield 20 mg (2%). The
physical constants of compound IX obtained by
the above procedures (a–f) were identical to those
reported in [8].
(DMSO-d6), δ, ppm: 5.86 s (1H, NH), 6.00 s (1H,
PhCH), 6.57–7.53 m (9H, C6H5, 6-H, 7-H, 8-H),
11.46 br.s (1H, NH, carbamoyl). Found, %: C 61.65;
H 4.83; N 17.84; S 10.22. C16H14N4OS. Calculated, %:
C 61.81; H 4.54; N 18.02; S 10.29.
3-[α-(2-Benzimidazolylsulfanyl)benzyl]-1,2-di-
hydroquinoxalin-2-one (VII). A solution of 0.50 g of
quinoxaline I and 0.31 g of 2-sulfanylbenzimidazole in
10 ml of DMSO was stirred for 6 h, and the mixture
was left to stand for 2 days. The mixture was poured
into water, and the precipitate was filtered off and
washed with a 5% aqueous solution of sodium
carbonate, water, and 2-propanol. Yield 0.60 g (85%),
mp >160°C (decomp., from dioxane). IR spectrum,
ν, cm–1: 1615 (C=N), 1665 (C=O), 2200–3570 (NH).
1H NMR spectrum (DMSO-d6), δ, ppm: 6.64 s (1H,
PhCH), 7.05–7.47 m (12H, C6H5, 6-H, 7-H, 8-H, 4'-H,
5'-H, 6'-H, 7'-H), 7.78 d (1H, 5-H, J = 7.83 Hz),
12.46 br.s (1H, NH, carbamoyl). Found, %: C 68.71;
H 4.25; N 14.82; S 8.50. C22H16N4OS. Calculated, %:
C 68.73; H 4.20; N 14.57; S 8.34.
3-[α-(2-Benzothiazolylsulfanyl)benzyl]-1,2-di-
hydroquinoxalin-2-one (VIII). A solution of 0.80 g of
quinoxaline I and 0.55 g of 2-sulfanylbenzothiazole in
10 ml of DMSO was stirred for 6 h, and the mixture
was left to stand for 7 days. The precipitate was
filtered off and washed with 2-propanol, a 5% aqueous
solution of sodium carbonate, and water. Yield 1.06 g
(90%), mp >170°C (decomp., from DMSO). IR spec-
trum, ν, cm–1: 1610 (C=N), 1670 (C=O), 2300–3220
1
3-[α-(1-Acetoxy-2-benzimidazolyl)benzyl]-1,2-
dihydroquinoxalin-2-one (XII). A solution of 0.2 g of
quinoxaline VII in a mixture of 2 ml of acetic
anhydride and 2 ml of acetic acid was heated for 1 min
under reflux and left overnight. The precipitate was
filtered off and washed with 2-propanol. Yield 0.21 g
(95%), mp 252–254°C (from DMSO). IR spectrum,
ν, cm–1: 1620 (C=N), 1670 (C=O, lactam), 1715
(NH). H NMR spectrum (DMSO-d6), δ, ppm: 6.87 s
(1H, PhCH), 7.25–7.66 m (10H, Harom), 7.88 d (1H,
Harom, J = 7.50 Hz), 7.98 d.d (1H, Harom, J = 7.50,
7.50 Hz), 8.07 d (1H, Harom, J = 7.50 Hz), 12.73 br.s
(1H, NH). Found, %: C 65.96; H 3.75; N 10.26;
S 15.90. C22H15N3OS2. Calculated, %: C 65.81; H 3.77;
N 10.47; S 15.97.
1
1-Acetylimino-4-oxo-3-phenyl-4,5-dihydrothia-
zolo[3,4-a]quinoxaline (IX). a. A solution of 1.00 g of
isothioureide VI in 20 ml of acetic acid was heated for
25 h under reflux. The mixture was cooled, and the
precipitate was filtered of and washed with 2-propanol.
Yield 0.12 g (11%), mp 341–343°C.
(C=O, acetyl), 2380–3220 (NH). H NMR spectrum
(DMSO-d6), δ, ppm: 2.81 s (3H, CH3), 6.97 s (1H,
PhCH), 7.25–7.39 m (7H, Harom), 7.48–7.59 m (2H,
Harom), 7.67 d (2H, Harom, J = 6.90 Hz), 7.72–7.78 m
(1H, Harom), 7.84 d (1H, Harom, J = 7.34 Hz), 12.47 br.s
(1H, NH). Found, %: C 67.46; H 4.08; N 13.36;
S 7.67. C24H18N3O2S. Calculated, %: C 67.59; H 4.25;
N 13.14; S 7.52.
3-Benzyl-1,2-dihydroquinoxalin-2-one (XIII).
A solution of 1.55 g of compound I and 0.48 g of
b. A solution of 1.00 g of isothioureide VI in 10 ml
of acetic anhydride was heated for 1 min under reflux
(after 20 s, crystals began to separate from the
solution). The mixture was cooled, and the precipitate
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FUSED POLYCYCLIC NITROGEN-CONTAINING HETEROCYCLES: VII.
533
thiourea in 15 ml of dioxane was heated for 4 h under
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1610 (C=N), 1660 (C=O), 2520–3220 (NH). H NMR
spectrum (DMSO-d6), δ, ppm: 4.39 s (2H, PhCH2),
7.19–7.39 m (7H, C6H5, 6-H or 7-H, 8-H), 7.48 d.d
(1H, 7-H or 6-H, J = 7.50, 7.50 Hz), 7.77 d (1H, 5-H,
J = 8.00 Hz), 12.45 br.s (1H, NH). Satisfactory
analytical data were obtained after repeated recrys-
tallizations.
4. Fedotov, K.V. and Romanov, N.N., Khim. Geterotsikl.
Soedin., 1989, no. 12, p. 1680.
5. Adegoke, E.A. and Babajide, A., J. Heterocycl. Chem.,
1983, vol. 20, p. 1513.
6. Eur. Patent no. 387887, 1990; Chem. Abstr., 1990,
vol. 114, no. 102051.
Methyl 2-hydroxy-2-(4-oxo-3-phenyl-4,5-dihy-
dro-1H-thiazolo[3,4-a]quinoxalin-1-ylideneamino)-
5-phenyl-2,3-dihydrothiazole-4-carboxylate (XV).
A solution of 1.20 g of KSCN in 5 ml of acetonitrile
was added to a mixture of 2.50 g of chloropyruvate
XIV and 3 ml of acetonirile. The mixture was stirred
for 6 h and left overnight. The precipitate of inorganic
salts was filtered off, a solution of 1.27 g of
o-phenylenediamine in 10 ml of acetic was added to
the filtrate, and the mixture was stirred for 1 h under
reflux. It was then cooled, and the precipitate was
filtered off and washed with 2-propanol. Yield 0.40 g
(8%), mp 339–341°C (DMSO). IR spectrum, ν, cm–1:
1672 (C=O, amide), 1722 (C=O, ester), 2650–3220
7. Mamedov, V.A. and Levin, Ya.A., Khim. Geterotsikl.
Soedin., 1996, no. 12, p. 1005.
8. Mamedov, V.A., Kalinin, A.A., Gubaidullin, A.T., Nur-
khametova, I.Z., Litvinov, I.A., and Levin, Ya.A.,
Khim. Geterotsikl. Soedin., 1999, no. 12, p. 1664.
9. Horner, V.L., Schwenk, U., and Junghanns, E., Justus
Liebigs Ann. Chem., 1953, vol. 579, p. 212.
10. Johnstone, R.A.W. and Povall, T.J., J. Chem. Soc.,
Perkin Trans. 1, 1975, no. 14, p. 1424.
11. Griffin, T.S., Woods, T.S., and Klayman, D.N., Adv.
Heterocycl. Chem., 1975, vol. 18, p. 99.
12. Shawali, A.S. and Abdelhamid, A.O., J. Heterocycl.
Chem., 1976, vol. 13, p. 45.
13. Scmidt, R.R. and Huth, H., Tetrahedron Lett., 1975,
1
(NH, OH). H NMR spectrum (DMSO-d6), δ, ppm:
no. 1, p. 33.
3.37 s (3H, CH3), 7.28–7.65 m (15H, 2C6H5, 6-H, 7-H,
8-H, NH, OH), 9.74 d (1H, 9-H, J = 8.5 Hz), 11.52 br.s
(1H, NH, lactam). Mass spectrum, m/z (Irel, %): 529
(10), 528 (30), 510 (25), 543 (24), 452 (55), 350 (11),
320 (33), 293 (42), 266 (100), 237 (11), 236 (68), 235
(39), 234 (40), 206 (26), 205 (31), 121 (67), 105 (18),
89 (12), 77 (19). Found, %: C 65.96; H 3.75; N 10.26;
S 15.90. C25H17N4O4S2. Calculated, %: C 65.81;
H 3.77; N 10.47; S 15.97.
14. Seitz, V.G., Mohr, R., Overheu, W., Allmann, R., and
Nagel, M., Angew. Chem., 1984, vol. 96, p. 885.
15. Mamedov, V.A., Efremov, Yu.Ya., Valeeva, V.N., Rizva-
nov, I.Kh., Kataeva, O.N., Antokhina, L.A., and Nuret-
dinov, I.A., Zh. Org. Khim., 1993, vol. 29, p. 1042.
16. Rizvanov, I., Mamedov, V., Efremov, Yu., and Pod-
valni, E., Adv. Mass Spectrom., 2001, vol. 15, p. 733.
17. Fort, R.C., Cheeseman, G.W.H., and Taylor, E.C.,
J. Org. Chem., 1964, vol. 29, p. 2440.
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 03-03-32865).
18. Davey, D.D., Erhardt, P.W., Cantor, E.H., Green-
berg, S.S., Ingebretsen, W.R., and Wiggins, J., J. Med.
Chem., 1991, vol. 34, p. 2671.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 4 2004