Fused polycyclic nitrogen-containing heterocycles 20. Thiazolo[3,4-a] quinoxalines from 4-hydroxy-2-phenyliminothiazolidines and C-substituted 1,2-phenylenediamines

Article abstract of DOI:10.1007/s11172-009-0029-z

The condensation of 4-hydroxy-3,5-diphenyl-2-phenyliminothiazolidine with 4,5-dimethyl-1,2-phenylenediamine affords 7,8-dimethyl-3-phenyl-1- phenyliminothiazolo[3,4-a]quinox-alin-4(5 H)- one; the condensation with 1,2-phenylenediamines containing differen

Full text of DOI:10.1007/s11172-009-0029-z

Russian Chemical Bulletin, International Edition, Vol. 58, No. 1, pp. 191—202, January, 2009
191
Fused polycyclic nitrogenꢀcontaining heterocycles
20.* Thiazolo[3,4ꢀa]quinoxalines from 4ꢀhydroxyꢀ
2ꢀphenyliminothiazolidines and Cꢀsubstituted 1,2ꢀphenylenediamines**
V. A. Mamedov, N. A. Zhukova, T. N. Beschastnova, A. T. Gubaidullin, Ya. A. Levin, and I. A. Litvinov
A. E. Arbuzov Institute of Organic and Physical Chemistry,
Kazan Research Center of the Russian Academy of Sciences,
8 ul. Akad. Arbuzova, 420088 Kazan, Russian Federation.
Fax: +7 (843 2) 73 2253. Eꢀmail: mamedov@iopc.knc.ru
The condensation of 4ꢀhydroxyꢀ3,5ꢀdiphenylꢀ2ꢀphenyliminothiazolidine with 4,5ꢀdimethylꢀ
1,2ꢀphenylenediamine affords 7,8ꢀdimethylꢀ3ꢀphenylꢀ1ꢀphenyliminothiazolo[3,4ꢀa]quinoxꢀ
alinꢀ4(5H)ꢀone; the condensation with 1,2ꢀphenylenediamines containing different substituꢀ
ents at positions 4 and 5 gives both theoretically possible isomeric thiazolo[3,4ꢀa]quinoxalines,
which differ in the distribution of these substituents between positions 7 and 8 in the benzene
ring of the quinoxaline system. 3aꢀHydroxyꢀ7,8ꢀdimethylꢀ3ꢀphenylꢀ1ꢀphenyliminoꢀ3,3aꢀdiꢀ
hydrothiazolo[3,4ꢀa]quinoxalinꢀ4(5H)ꢀone was isolated and characterized as the intermediate
of the reaction giving rise to thiazolo[3,4ꢀa]quinoxaline from 4,5ꢀdimethylꢀ1,2ꢀphenyleneꢀ
diamine. This intermediate is a covalent hydrate of the final product.
Key words: Hantzsch reaction, 4ꢀhydroxythiazolidines, thiazolo[3,4ꢀa]quinoxalines,
IR spectroscopy, NMR spectroscopy, Xꢀray diffraction study.
trophilic reagents are of special interest. The condensaꢀ
tion of dicarbonyl compounds with 1,2ꢀdiaminoazines16
can be referred to as examples of these reactions.
Earlier,17—20 we have shown that the reaction of
the stable intermediate of the Hantzsch reaction, viz.,
4ꢀhydroxyꢀ4ꢀmethoxycarbonylꢀ3,5ꢀdiphenylꢀ2ꢀphenylꢀ
iminothiazolidine (1a), with 1,2ꢀphenylenediamine (2a)
in boiling acetic acid readily leads to the condensation
accompanied by elimination of methanol, acetanilide,
Quinoxaline derivatives exhibit a broad spectrum of
biological activities, including antibacterial, antitumor,
and antiviral activities (in particular, antiꢀHIV activity).2—4
The quinoxaline system and its azoloꢀ and azinoꢀfused
derivatives are components of various biologically imporꢀ
tant compounds and medicines. The synthesis of these
compounds is often carried out with the use of functionꢀ
alized quinoxalines and their fused derivatives as key comꢀ
pounds. For example, quinoxalines and their derivatives
were used as template agents in the synthesis of GABA/
diazepine receptor agonists and antagonists,5 cAMPꢀ
and cGMP phosphodiesterase inhibitors,6 A1 and A2a
adenosine agonists,7 and many other pharmacologically
active substances.8—11 The discovery of nalidixic acid,12
which is an efficient antibacterial synthetic medication13
and is a derivative of the quinoxaline isomer, viz.,
pyrido[2,3ꢀb]pyridine, gave a strong impetus to the deꢀ
velopment of methods of synthesis and chemistry of
quinoxalines.
Scheme 1
The main approaches to the synthesis of fused pyraꢀ
zines and quinoxalines have been described previously.14,15
Among cyclization reactions giving rise to fused azaꢀ
heterocyclic compounds, the reactions of compounds
containing two nucleophilic groups with bifunctional elecꢀ
* For Part 19, see Ref. 1.
** Dedicated to Academician A. I. Konovalov on his 75th birthday.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 190—200, January, 2009.
1066ꢀ5285/09/5801ꢀ0191 © 2009 Springer Science+Business Media, Inc.

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Mamedov et al.
Scheme 2
and water to form 3ꢀphenylꢀ1ꢀphenyliminoꢀ4,5ꢀdihydroꢀ
thiazolo[3,4ꢀa]quinoxalinꢀ4ꢀone (3a) (Scheme 1).
With the aim of extending the scope of the method for
the synthesis of thiazolo[3,4ꢀa]quinoxalines, we investiꢀ
gated the pathways of the reactions of 4ꢀhydroxyꢀ2ꢀpheꢀ
nylꢀ (1a) and 2ꢀthiazolꢀ2ꢀyliminothiazolidine (1b) with
several 1,2ꢀphenylenediamines containing the monoꢀ or
disubstituted benzene ring.
In particular, the condensation of hydroxythiazolidine
1b should afford 1ꢀthiazolyliminothiazolo[3,4ꢀa]quinoxꢀ
alines containing an additional weakly basic thiazole
nitrogen atom compared to the condensation products of
hydroxythiazolidine 1a. This holds promise for the design
of biologically active thiazolo[3,4ꢀa]quinoxalines.
Unlike hydroxythiazolidine 1a containing two phenyl
substituents at the nitrogen atoms (hereinafter, this comꢀ
pound is referred to as structurally “symmetrical”), which
has been characterized previously,17—20 hydroxythiazoliꢀ
dine 1b containing the phenyl and thiazolꢀ2ꢀyl substituꢀ
ents at the nitrogen atoms is “unsymmetrical.” Hence,
the condensation of 1b with 1,2ꢀphenylenediamines can
afford a larger number of regioisomers of the final triꢀ
cyclic compound. Analogously, unlike “symmetrical”
diamines (unsubstituted 1,2ꢀphenylenediamine (2a)17—20
and 4,5ꢀdifluoroꢀ1,2ꢀphenylenediamine19 used earlier and
4,5ꢀdimethylꢀ1,2ꢀphenylenediamine (2b) under study),
which can give only one final product 3, monosubstituted
structurally “unsymmetrical” 4ꢀmethylꢀ1,2ꢀphenylenediꢀ
amine (2c) and 4ꢀnitroꢀ1,2ꢀphenylenediamine (2d) can
give two isomeric final products, which differ in the posiꢀ
tion of the substituent in the benzene fragment of the
quinoxaline system.19,20 In the present study, we investiꢀ
gated the isomeric composition of thiazolo[3,4ꢀa]quinoxꢀ
alines produced by the reactions of hydroxythiazolidines
1 with 1,2ꢀphenylenediamines 2b—d substituted at the
benzene ring and considered the mechanisms of their
formation.
of benzeneꢀunsubstituted thiazolo[3,4ꢀa]quinoxaline 3a.20
The introduction of methyl groups at positions 7 and 8 of
the thiazolo[3,4ꢀa]quinoxaline system not only enhances
the stability of intermediate covalent hydrate 3b´ but
also causes an increase in the melting point of thiazoloꢀ
[3,4ꢀa]quinoxaline 3b. The melting points of compound
3b and its benzeneꢀunsubstituted analog 3a are 352—355 °C
and 301—301.5 °C, respectively.
The structure of thiazolo[3,4ꢀa]quinoxaline 3b was
confirmed also by Xꢀray diffraction (Fig. 1). Compound
C(51)
C(13)
C(14)
S(50)
C(12)
C(15)
O(50)
Results and Discussion
C(52)
C(16)
Reactions of “symmetrical” 4ꢀhydroxythiazolidine 1a
with substituted 1,2ꢀphenylenediamines. The reaction of
4ꢀhydroxythiazolidine 1a with 1,2ꢀdiaminoꢀ4,5ꢀdimethylꢀ
benzene (2b) under standard conditions (in boiling acetic
acid), like the reactions with 1,2ꢀdiaminobenzene (2a)
and 1,2ꢀdiaminoꢀ4,5ꢀdifluorobenzene,19 affords the
expected tricyclic compound 3b as the only final product
(Scheme 2).
The structure of compound 3b was confirmed by
1H NMR spectroscopy. The NMR spectrum of thiazoloꢀ
[3,4ꢀa]quinoxaline 3b shows three singlets for the protons
H(6), H(9), and NH and the characteristic proton signals
of two phenyl substituents occupying different positions.
The signals for the protons H(6) and H(9) are shifted
upfield by 0.2 ppm compared to the corresponding signals
C(11)
S(2)
N(1)
C(1)
C(36)
C(31)
C(35)
C(34)
C(8A)
C(8)
C(7)
C(3)
C(3A)
C(9)
C(9A)
N(10)
C(33)
C(32)
C(5A)
N(5)
C(4)
O(4)
C(6)
C(7A)
Fig. 1. Molecular structure of compound 3b in the crystal.
Nonhydrogen atoms are represented by displacement ellipsoids
at the 50% probability level; the H atoms are represented by
spheres with an arbitrary radius. The DMSO molecule is shown
in the site with a higher occupancy.

Thiazolo[3,4ꢀa]quinoxalines
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 1, January, 2009
193
Table 1. Ratios* of the final compound thiazolo[3,4ꢀa]quinoxꢀ
aline 3b to the intermediate (covalent hydrate) 3b´ in the reacꢀ
tion mixture depending on the time of the reaction 1a + 2b (t)
3b crystallizes with the involvement of DMSO molecules
in a ratio of 1 : 1. In the crystal structure, the solvent
molecule being disordered over two positions with an
occupancy ratio of 0.87 : 0.13.
The thiazolo[3,4ꢀa]quinoxaline moiety in the molꢀ
ecule is planar within 0.045(2) Å. The dihedral angle
between the plane of the thiazole ring and the planes of
the phenyl substituents C(11)—C(16) and C(31)—C(36)
are 82.4 and 52.9°, respectively.
t/min
3b/3b´
Yield of 3b + 3b´ (%)
0.1
5
20
60
62/38
69/31
75/25
100/0
76
78
79
84
The presence of the solvent molecules hinders the
formation of hydrogenꢀbonded dimers with the involveꢀ
ment of the carbamoyl group, which is typical of interꢀ
molecular interactions in crystals of pyrroloꢀ and azoloꢀ
quinoxalines.21—24
* The values were calculated from the integral intensities of
the signals for the protons H(9) and the methyl groups in the
1H NMR spectra of the crude reaction products.
the final thiazolo[3,4ꢀa]quinoxaline 3a in quantitative
yield (see Scheme 1), refluxing of the reaction mixture for
1 h is required for the reaction under consideration to
proceed. Otherwise, the reaction affords a mixture of
the final thiazolo[3,4ꢀa]quinoxaline 3b and its covalent
hydrate 3b´ (see Scheme 2 and Table 1). This is evidenced
by 1) the molecular ion peaks at m/z 397 and 415 assigned
to compounds 3b and 3b´ in the mass spectra of the crude
products obtained after refluxing the reaction mixture for
0.1, 5, and 20 min; 2) the presence of a double set of all
signals and the singlets for the protons at the C(3) atom
and the hydroxy group at δ 5.45 and 7.20, respectively, in
In the crystal structure of compound 3b, the DMSO
molecule forms a hydrogen bond with the NH group of
the tricyclic fragment (H(5)...O(50), 2.01 Å; N(5)...O(50),
2.87(1) Å; N(5)—H(5)...O(50), 173°). Based on the forꢀ
mal criteria25 for the presence of π—π interactions (the
distances between the centers of aromatic rings (or aroꢀ
matic systems) shorter than 6.0 Å and the angle between
the normal to the plane of one of the rings and the vector
between the centers of the rings smaller than 60°) and
taking into account the published data,26 we found that
thiazoloquinoxaline molecules 3b in the crystal structure
form centrosymmetric dimers through π—π interactions
between the aromatic systems of the tricyclic fragments of
the molecules (the distances between the arbitrary centers
of the tricyclic systems of the molecules is 4.10 Å, the
dihedral angle between their mean planes is 0°, and the
shortest distance between these planes is 3.49 Å). It should
be noted that these π dimers are arranged in the crystal
structure in a herringbone fashion so that pairs of DMSO
solvent molecules are located in the cavities formed
by eight thiazoloquinoxaline molecules 3b (Fig. 2). The
disorder of the DMSO molecules indicates that these
molecules are not closely packed. This is also evidenced
by the low packing coefficient (68.0%).
1
the H NMR spectra; 3) the presence, along with other
bands, an OH absorption band (3440 cm–1) in the IR specꢀ
trum. In spite of the fact that two methyl groups in the
compounds under consideration are nonequivalent, the proton
signals of these groups appear in the 1H NMR spectra as one
singlet, whose integral intensity corresponds to six protons
(δ 2.21 and 2.18 for compounds 3b and 3b´, respectively).
The reaction performed at 80 5 °C for 50 min gives
rise to pure crystals of compound 3b´, as evidenced by
elemental analysis data and spectroscopic characteristics.
Since compound 3b´ contains two asymmetric cenꢀ
ters, it would be expected that this compound will be
obtained as a diastereomeric mixture. However, the
signals for the protons at the C(3), C(6), and C(9) atoms
Unlike the reaction with unsubstituted 1,2ꢀphenyleneꢀ
diamine (2a), which is completed within 3—5 min to give
1
and for the protons of the methyl groups in the H NMR
spectra of compound 3b´ are identical to the signals for
the corresponding protons in samples produced in differꢀ
ent syntheses. Hence, the highly stereoselective formaꢀ
tion of covalent hydrate 3b´ is highly probable.
Under reflux in AcOH, i.e., under the conditions of
the synthesis of thiazolo[3,4ꢀa]quinoxaline 3b, compound
3b´ is quantitatively dehydrated to give 3b (see Scheme 2).
This confirms the fact that covalent hydrate 3b´ is the
intermediate in the synthesis of thiazoloquinoxaline 3b.
The most probable route to the final product 3b from the
starting compounds through intermediate 3b´ is presented
in Scheme 3. It is most probable that openꢀchain isomer 4
(see Refs 17—20 and 24) rather than cyclic isomers αꢀ1a
or βꢀ1a are involved in the formation of intermediate 3b´
(Scheme 4).
Fig. 2. Encapsulation of two DMSO molecules by eight molꢀ
ecules 3b in the crystal structure. The DMSO molecules are
represented in vanꢀderꢀWaals radii in the sites with a higher
occupancy. The H atoms are omitted.

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Mamedov et al.
Scheme 3
Scheme 5
Scheme 4
R1 = Me, R2 = H (2c, 5a, 6a); R1 = NO2, R2 = H (2d, 5b, 6b)
crude product obtained in the reaction of hydroxythiazoꢀ
lidine 1a with 4ꢀnitroꢀ1,2ꢀphenylenediamine (2d). Howꢀ
ever, the diagnostic signal for the proton H(9) (δ 10.42) of
the major product 6b, whose integral intensity is 9 times
higher than the intensity of the signal of the minor prodꢀ
uct 5b, appears as a singlet, whereas the diagnostic signal
for the proton H(9) (δ 9.62) of the minor product 5b
appears as a doublet with the vicinal constant 3J = 8.9 Hz.
Individual compound 6b was isolated by recrystallization
of the mixture of the isomers. Earlier, we have established
the structure of compound 6b by Xꢀray diffraction.19
In the mechanism of formation of the thiazolo[3,4ꢀa]ꢀ
quinoxaline system, which we have suggested previꢀ
ously,19,20 the linear (4) and cyclic tautomers of the starting
4ꢀhydroxyꢀ3,5ꢀdiphenylꢀ2ꢀphenyliminothiazolidine 1a are
involved in the first step of the reaction (see Scheme 4).
Therefore, the reactions of 4ꢀsubstituted “unsymmetriꢀ
cal” 1,2ꢀphenylenediamines can afford two isomeric prodꢀ
ucts 5 or 6 depending on which nitrogen atom is subjected
to the primary attack (Schemes 6 and 7). This is consisꢀ
tent with the aboveꢀconsidered experimental results.
In each possible reaction pathways, viz., amidation
(A), amination (B), and imination (C), the first step
involves different electrophilic substitution modes at the
N atom of the amino group of 4ꢀsubstituted 1,2ꢀpheꢀ
nylenediamines. In the case of electronꢀdonating subꢀ
stituents (in our case, the methyl group), which activate
the amino group in the para position to the electrophilic
attack, the pathways B or C should afford compounds
containing the substituent at position 7 as the major prodꢀ
ucts; in the case of electronꢀwithdrawing substituents (in
our case, the nitro group), which deactivate the amino
Previously,19,20 when studying the reactions of 4ꢀhydroxyꢀ
thiazolidine 1a with “unsymmetrical” 4ꢀmethylꢀ1,2ꢀpheꢀ
nylenediamine (2c) and 4ꢀnitroꢀ1,2ꢀphenylenediamine
(2d), we have detected only one reaction product, viz.,
7ꢀmethyl derivative 5a and 8ꢀnitro derivative 6b, respecꢀ
tively. However, the more thorough study of the reaction
1
mixtures by H NMR spectroscopy showed that both
reactions afford two compounds (Scheme 5), which can
be separated by column chromatography.
In particular, this is evidenced by the presence of a
1
double set of all signals in the H NMR spectrum of the
crude product obtained in the reaction of 4ꢀhydroxyꢀ
thiazolidine 1a with diamine 2c. The integral intensity of
the diagnostic signal for the proton H(9), which is split into
a doublet by the vicinal proton H(9) (δ 9.29, 3J = 8.9 Hz)
of the major isomer, viz., 7ꢀmethylthiazolo[3,4ꢀa]quinoxꢀ
aline 5a, is 1.5 times higher than the integral intensity of
the singlet for the same proton (δ 9.28) in its 8ꢀmethyl
isomer 6a (the integral intensity ratio is the same). An
1
analogous H NMR spectral pattern is observed for the

Thiazolo[3,4ꢀa]quinoxalines
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 1, January, 2009
195
Scheme 6
R is an electronꢀdonating substituent
Scheme 7
R is an electronꢀwithdrawing substituent

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Mamedov et al.
Scheme 8
Th =
storage for one day show three groups of signals consisting
of six singlets for the methoxy protons (δ 3.32, 3.41, 3.49,
3.72, 3.73, and 3.86), four singlets for the methine protons
(δ 5.23, 5.30, 5.43, and 5.46), first of which is broadened
and corresponds to three protons, and multiplets for
aromatic protons (δ 6.89—7.65). For a solution of the
product under study, the total integral intensity ratio for the
signals of these tautomeric groups is still equal to 1 : 3 : 12
(at least for one day), and the chemical shifts remain
unchanged. The percentage of the tautomers in the soluꢀ
tion estimated from the integral intensities of the signals
for the methoxy and methine protons is approximately
28, 3, 8, 12, 26, and 23%.
group, these pathways should give rise to products conꢀ
taining the substituent at position 8. We experimentally
observed this distribution of isomers.
If the pathway A would play an essential role, the
regioselectivity would be opposite to that observed
experimentally; consequently, the contribution of this
reaction pathway to the final result is small.
Reactions of “unsymmetrical” 4ꢀhydroxythiazolidine 1b
with substituted 1,2ꢀphenylenediamines. 4ꢀHydroxythiazoꢀ
lidine 1b, like its “symmetrical” analog 1a, which we have
considered earlier,24 exists as a tautomeric mixture conꢀ
sisting of the openꢀchain and diastereomeric cyclic forms.
However, unlike analog 1a, 4ꢀhydroxythiazolidine 1b has
two isomeric cyclic forms, resulting in a more complex
tautomeric equilibrium (Scheme 8).
The origin of tautomerism resulting in the compliꢀ
1
cation of the H NMR spectra is apparently the same as
1
that of the aboveꢀmentioned tautomerism of compound
1a.15,18—20,24 Some equilibria are presented in Scheme 8.
It should be noted that only one thiazolylimine isomer
was isolated in the reaction of 4ꢀhydroxythiazolidine 1b
with unsubstituted 1,2ꢀphenylenediamine (2a),19 whereas
both expected thiazolo[3,4ꢀa]quinoxalines 3b and 9a
were isolated in a ratio of 1 : 1.4 in the reaction with
4,5ꢀdimethylꢀ1,2ꢀdiaminobenzene (2b) (Scheme 9). The
ratio of the yields of these thiazoloquinoxalines depends
Based on the H NMR and IR spectra of 4ꢀhydroxyꢀ
thiazolidine 1b, the ratio of the components in these
mixtures strongly depends on the conditions under which
the spectra are recorded, the nature of the substituents,
and the conditions of isolation and purification of the
products. The detailed consideration of the regioꢀ and
diastereomeric composition is beyond the scope of the
1
present study. However, let us note that the H NMR
spectra of the sample prepared from a solution after its

Thiazolo[3,4ꢀa]quinoxalines
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 1, January, 2009
197
Scheme 9
Scheme 10
1
cated by the fact that the H NMR spectrum of the
crude product shows three doublets for the proton H(9) at
δ 10.69, 10.39, and 9.84 in the region diagnostic for
thiazolo[3,4ꢀa]quinoxalines. Compound 9d that was
formed in the highest yield and is characterized by the
chemical shift of the diagnostic proton at δ 10.69 was
isolated preparatively. The structure of compound 9d was
established by Xꢀray diffraction (Fig. 3). Small spinꢀspin
coupling constants (J = 2.5 Hz) for the doublets of the
proton H(9) at δ 10.69 and 10.39 indicate that these
signals belong to 8ꢀnitroꢀsubstituted thiazolo[3,4ꢀa]ꢀ
quinoxalines 9d and 6b, respectively; consequently, the
Th =
on the competition between the elimination of the
nucleofuges PhNHAc or ThNHAc from the same interꢀ
mediate I in an acidic medium.
The use of “unsymmetrical” 4ꢀmonosubstituted
1,2ꢀphenylenediamines in the reaction with thiazolidine
1b can lead to the formation of four isomers (two pairs)
of tricyclic products, which differ in the nature of subꢀ
stituents in the imine fragment and the benzene ring.
Scheme 11
1
Actually, the H NMR spectrum of the crude product
obtained in the reaction of 4ꢀhydroxythiazolidine 1b with
4ꢀmethylꢀ1,2ꢀphenylenediamine (2c) (Scheme 10) shows
four signals for the diagnostic proton H(9). Two of these
signals appear as singlets at δ 9.27 and 9.52 (compounds
6a and 9c containing the 8ꢀMe group), and two other
signals appear as doublets at δ 9.29 (3J = 8.9 Hz) and 9.55
(3J = 8.4 Hz) (compounds 5a and 9b containing the 7ꢀMe
group). The formation of four compounds (two pairs of
1
isomers) is evidenced also by the fact that the H NMR
spectrum contains, along with other signals, two groups
of signals consisting of four singlets each, which correꢀ
spond to methyl and carbamoyl protons. The ratio of the
major thiazolylimine products (9b,c) to the minor phenylꢀ
imine products (5a and 6a) is 93 : 7. Compound 9b that
was formed in the highest yield was isolated preparatively.
The condensation of 4ꢀhydroxythiazolidine 1b with
4ꢀnitroꢀ1,2ꢀphenylenediamine (2d) (Scheme 11) affords
a mixture of three out of four possible products, as indiꢀ

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Mamedov et al.
N(5)...O(50), 2.834(3) Å; N(5)—H(5)...O(50), 162°). The
stacking effect is observed in the crystal structure of comꢀ
pound 9d. Thus, the electronic systems of the tricyclic
and thiazole moieties of the molecule interact with the
thiazole ring and the tricyclic moiety, respectively (in a
headꢀtoꢀtail fashion) of the molecules related to the
reference molecule by the translation 1 along the 0x
axis. The distance between the arbitrary center of the
tricyclic moiety and the center of the thiazole ring of
the adjacent molecule is 3.57 Å. The dihedral angle between
their mean planes is 0°. The shortest distance between the
planes of the molecules is 3.37 Å. The tetragonal packing
of the molecular stacks gives rise to pseudochannels, which
are occupied by the solvent molecules (Fig. 4). However,
the packing coefficient is low (the calculated coefficient
is 68.8%).
The factors determining the position of the methyl
and nitro groups in the reaction products of 4ꢀhydroxyꢀ
thiazolidine 1b with “unsymmetrical” diamines 2c,d and
the ratio of isomeric products are the same as those
observed in the reactions of “symmetrical” hydroxythiazoꢀ
lidine 1a. The explanation of the predominant formation
of 1ꢀthiazolylimino derivatives of thiazolo[3,4ꢀa]quinoxꢀ
alines in the reactions of hydroxythiazolidine 1b with both
“unsymmetrical” diamines under study is problematic.
Since the reaction is performed in acetic acid, the higher
basicity of the thiazolyl group compared to that of the
phenylamino group (pKa of 2ꢀaminothiazole is 5.39,27
pKa of aniline is 4.6 (see Ref. 28)) should lead to the
predominant protonation of the thiazole fragment and
elimination of aminothiazole K as a result of cyclization
of intermediate J (Scheme 12) to form 1ꢀphenylimino
derivatives of thiazoloquinoxaline 5 and 6. However, this
is not observed; instead, the phenylamino group is elimiꢀ
nated and the reaction affords 1ꢀthiazolylimino derivaꢀ
O(50)
C(13)
C(14)
C(50)
C(51)
C(52)
S(12)
N(15)
N(50)
C(11)
N(1)
C(1)
O(82)
N(8)
S(2)
C(3)
C(9A) N(10)
C(36)
C(35)
C(9)
O(81)
C(8)
C(3A)
C(5A)
C(31)
C(34)
C(7)
C(6)
C(32)
C(33)
O(4)
N(5)
C(4)
Fig. 3. Molecular structure of compound 9d in the crystal.
chemical shift of the diagnostic proton at δ 10.39 is
assigned to the latter compound. The doublet of the prodꢀ
uct with the chemical shift of the diagnostic proton at
δ 9.84 and the characteristic vicinal constant (3J = 9.4 Hz)
belongs to either 7ꢀnitroꢀsubstituted thiazolo[3,4ꢀa]ꢀ
quinoxaline 9e or compound 5b. The ratio of products 9d,
6b, and 9e in the crude mixture, which was calculated
from the integral intensities of the diagnostic signals for
1
the proton H(9) in the H NMR spectrum, is 71 : 26 : 3.
The singlets for the protons of the NH groups are characꢀ
terized by the same integral intensity ratio.
Returning to the aboveꢀconsidered products prepared
by the reactions of 4ꢀhydroxythiazolidine 1b with 4ꢀmethylꢀ
1,2ꢀphenylenediamine (2c) and 4ꢀnitroꢀ1,2ꢀphenyleneꢀ
diamine (2d), it should be noted that a comparison of
the positions, multiplicities, and integral intensities of the
protons of the thiazolyl and benzene rings in the tricyclic
system allowed us to assign the signals to the correspondꢀ
ing thiazolo[3,4ꢀa]quinoxaline derivatives.
Compound 9d also crystallizes with DMF solvent
molecules in a ratio of 1 : 1. Molecule 9d is planar within
experimental error (0.02(2) Å), the nitro group and the
thiazole substituents also lying in the plane of the tricyclic
fragment. Moreover, the planar DMF molecule also lies
virtually in the plane of molecule 9d. The dihedral angle
between the plane of the DMF molecule and the mean
plane of the tricyclic moiety of molecule 9d is 2.8°. The
distances from different atoms of the tricyclic moiety
to the plane of the DMF molecule are in the range of
0.44—0.58 Å. The phenyl substituent C(31)—C(36) is the
only fragment of the molecule, which deviates from the
plane of the tricyclic moiety and is nearly perpendicular
to the latter (the dihedral angle is 63.5°). As in the crystal
structure of compound 3b, the DMF solvent molecule
hinders the formation of hydrogenꢀbonded dimers of
molecules 9d in the crystal structure through classical
hydrogen bonds. The solvent molecule is involved in
hydrogen bonding; this hydrogen bond is formed between
the carbonyl group of the DMF molecule and the hydroꢀ
gen atom of the amino group (H(5)...O(50), 2.00 Å;
Fig. 4. Formation of pseudochannels filled by DMF molecules
in the crystal structure of compound 9d. The projection approxiꢀ
mately along the 0a axis. The DMF molecules are represented in
vanꢀderꢀWaals radii. The H atoms are omitted.

Thiazolo[3,4ꢀa]quinoxalines
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 1, January, 2009
199
the aqueous layer was extracted with CH2Cl2 (2×20 mL). The
organic layer and the extract were combined and dried with
MgSO4. The solvent was evaporated. The residue was treated
with diethyl ether. Compound 1b was obtained in a yield of 4.3 g
(52%), m.p. 150—155 °C (PriOH). Found (%): C, 58.42;
H, 4.26; N, 9.98; S, 15.47. C20H17N3O3S2. Calculated (%):
C, 58.38; H, 4.16; N, 10.21; S, 15.58. IR (Nujol), ν/cm–1: 3500
(OH), 3189—3088, 1763 (C=O), 1737, 1630 (C=N), 1597, 1664,
tives 9 through the intermediate L. Like in the reactions
of unsubstituted 1,2ꢀphenylenediamine (2a) with “unsymꢀ
metrical” 4ꢀhydroxyꢀ3(5)ꢀpyridꢀ2ꢀylꢀ and 5(3)ꢀphenylꢀ
2ꢀenyliminothiazolidines and their picolyl homologs,
which we have described previously,23 this fact can be
attributed to the intramolecular transfer of the proton or
the acetyl group from the thiazole nitrogen atom to the
phenylamino nitrogen atom.
1
1492. H NMR (CDCl3), δ: 3.32, 3.41, 3.49, 3.72, 3.73, and
3.86 (all s, 3 H each, OMe); 5.23 (br.s, 3 H, 3 CH); 5.30, 5.43,
and 5.46 (all s, 3 H each, 3 CH); 6.89—7.65 (m, 6×14 H, 6×2 Ph,
6 H(4) and 6 H(5) thiazole, 6 OH). The percentage of tautomers
in the solution was ~28, 3, 8, 12, 26, and 23%. The total integral
intensity ratio of the methine, methoxy, and aromatic protons
is 1 : 3 : 12.
Scheme 12
3aꢀHydroxyꢀ7,8ꢀdimethylꢀ3ꢀphenylꢀ1ꢀphenyliminoꢀ
3,3aꢀdihydrothiazolo[3,4ꢀa]quinoxalinꢀ4(5H)ꢀone (3b´). A soluꢀ
tion of 1,2ꢀdiaminoꢀ4,5ꢀdimethylbenzene (2b) (0.05 g, 0.37 mmol)
and 4ꢀhydroxythiazolidine 1a (0.14 g, 0.37 mmol) in AcOH
(5 mL) was heated at 80 5 °C for 50 min. The yellow precipitate
that formed after cooling was filtered off. Compound 3b´
was obtained in a yield of 0.12 g (80%), m.p. 346—351 °C.
Found (%): C, 69.09; H, 5.06; N, 9.09; S, 8.01. C24H21N3O2S.
Calculated (%): C, 69.38; H, 5.09; N, 10.11; S, 7.72. IR, ν/cm–1
:
3370 (OH), 3181—2857 (NH), 1665 (C=O), 1638, 1617, 1593.
1H NMR, δ: 2.18 (s, 6 H, 2 Me); 5.45 (s, 1 H, CH); 6.81 (s, 1 H,
H(6)); 6.94 (d, 2 H, 2 oꢀH phenylimine, J = 7.6 Hz); 7.06 (dd,
1 H, pꢀH phenylimine, J = 7.3 Hz, J = 7.3 Hz); 7.20 (s, 1 H,
OH); 7.27 (dd, 1 H, pꢀHPh, J = 7.1 Hz, J = 6.5 Hz); 7.31 (dd,
2 H, 2 mꢀH phenylimine, J = 7.8 Hz, J = 7.6 Hz); 7.31 (dd,
2 H, 2 mꢀHPh, J = 7.8 Hz, J = 7.6 Hz); 7.64 (d, 2 H, 2 oꢀHPh
J = 7.1 Hz); 8.27 (s, 1 H, H(9)); 10.78 (s, 1 H, NH).
,
7,8ꢀDimethylꢀ3ꢀphenylꢀ1ꢀphenyliminothiazolo[3,4ꢀa]quinoxꢀ
alinꢀ4(5H)ꢀone (3b). A. A solution of 1,2ꢀdiaminoꢀ4,5ꢀdimethylꢀ
benzene (2b) (0.5 g, 3.67 mmol) and 4ꢀhydroxythiazolidine 1a
(1.42 g, 3.67 mmol) in AcOH (30 mL) was refluxed for 1 h. The
yellow crystals that precipitated were filtered off. Compound 3b
was obtained in a yield of 1.21 g (84%), m.p. 352—355 °C.
Found (%): C, 75.20; H, 4.65; N, 10.22; S, 8.02. C24H19N3OS.
Experimental
Calculated (%): C, 72.52; H, 4.82; N, 10.57; S, 8.07. IR, ν/cm–1
:
The 1H NMR spectra were recorded on a BrukerꢀAVANCEꢀ600
spectrometer operating at 600.00 MHz. The chemical shifts are
given on the δ scale (experimentally measured with respect to
DMSOꢀd6). The IR spectra were measured on a Vectorꢀ22
Fourierꢀtransform IR spectrometer (Bruker) in KBr pellets. The
melting points were determined on a Boetius hotꢀstage apparaꢀ
tus. The electronꢀimpact mass spectra were obtained on a
TRACE MS quadrupole mass spectrometer (ThermoQuest/
Finnigan) using a direct inlet system with water cooling.
4ꢀHydroxyꢀ4ꢀmethoxycarbonylꢀ3,5ꢀdiphenylꢀ2ꢀphenyliminoꢀ
thiazolidine (1a) was synthesized by the reaction of methyl
3ꢀchloroꢀ2ꢀhydroxoꢀ3ꢀphenylpropionate with N,N´ꢀdiphenylꢀ
thiourea according to a known procedure.24
4ꢀHydroxyꢀ4ꢀmethoxycarbonylꢀ2ꢀ(thiazolꢀ2ꢀyl)iminoꢀ
3,5ꢀdiphenylthiazolidine (1b). Sodium acetate (4.08 g, 0.05 mol)
was added to a solution of NꢀphenylꢀN´ꢀthiazolꢀ2ꢀylthiourea
(4.7 g, 0.02 mol) in CH2Cl2 (150 mL). The reaction mixture
was cooled to –15—–20 °C, and then a solution of methyl
chlorophenylpyruvate (4.15 g, 0.02 mol) in CH2Cl2 (20 mL) was
added dropwise. The reaction mixture was stirred at ~20 °C for
5 h and poured into water. The organic layer was separated, and
3140—2880 (NH), 1684 (C=O), 1612 (C=N), 1575, 1515.
1H NMR, δ: 2.21 (s, 6 H, 2 Me); 6.92 (s, 1 H, H(6)); 7.07 (d,
2 H, 2 oꢀH phenylimine, J = 7.8 Hz); 7.13 (dd, 1 H, pꢀH
phenylimine, J = 7.8 Hz, J = 6.7 Hz); 7.34—7.36 (m, 3 H,
2 oꢀHPh + pꢀHPh); 7.41 (dd, 2 H, 2 mꢀH phenylimine,
J = 7.8 Hz, J = 6.7 Hz); 7.45—7.48 (m, 2 H, 2 mꢀHPh); 9.21
(s, 1 H, H(9)); 11.09 (s, 1 H, NH).
B. A solution of compound 3b´ (100 mg) in AcOH (3 mL)
was refluxed for 45 min. The precipitate was filtered off. Comꢀ
pound 3b was obtained in a yield of 91 mg (95%). The characterꢀ
istics of this compound are identical to those of the compound
prepared according to the method A.
7,8ꢀDimethylꢀ3ꢀphenylꢀ1ꢀphenyliminothiazolo[3,4ꢀa]quiꢀ
noxalinꢀ4(5H)ꢀone (3b) and 7,8ꢀdimethylꢀ1ꢀ(thiazolꢀ2ꢀyl)iminoꢀ
3ꢀphenylthiazolo[3,4ꢀa]quinoxalinꢀ4(5H)ꢀone (9a) (a mixture
of isomers 3b + 9a in a percentage ratio of 41 : 59). A solution of
1,2ꢀdiaminoꢀ4,5ꢀdimethylbenzene (2b) (1.17 g, 1.2 mmol) and
4ꢀhydroxythiazolidine 1b (0.5 g, 1.2 mmol) in AcOH (30 mL)
was refluxed for 1.5 h. The reaction mixture was cooled. The
yellow crystals that precipitated were filtered off. A mixture
3b + 9a was obtained in a yield of 0.37 g (77%). The mixture was

200
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 1, January, 2009
Mamedov et al.
recrystallized from DMF. Compound 9a was obtained in a yield
of 0.18 g (38%), m.p. >350 °C. Found (%): C, 62.26; H, 4.28;
N, 14.16; S, 15.65. C21H16N4OS2. Calculated (%): C, 62.36;
H, 3.99; N, 13.85; S, 15.85. IR, ν/cm–1: 3044—2853 (NH),
IR, ν/cm–1: 3180—3020 (NH), 1679 (C=O), 1628 (C=N), 1590,
1574, 1529, 1504. 1H NMR, δ: 7.11—8.16 (m, 24 H, 4 Ph,
2 H(6), H(7), H(8)); 8.04 (d, 1 H, H(8), J = 9.2 Hz); 8.15 (d,
1 H, H(7), J = 8.9 Hz); 9.62 (d, 1 H, H(9), J = 8.9 Hz); 10.42
(s, 1 H, H(9)); 11.50 and 11.75 (both s, 1 H each, NH). The
mixture of isomers 5b + 6b was recrystallized from DMF. Comꢀ
pound 6b was obtained in a yield of 0.61 g (59%) as orange
crystals, m.p. 344—346 °C. Found (%): C, 61.61; H, 4.31;
N, 14.36; S, 6.58. C22H14N4O3S•DMF. Calculated (%):
C, 61.77; H, 4.38; N, 14.53; S, 6.73. IR, ν/cm–1: 3180—2853
(NH), 1678 (C=O), 1628 (C=N), 1590, 1573, 1529, 1502.
1H NMR, δ: 7.13 (d, 2 H, 2 oꢀH phenylimine, J = 7.9 Hz); 7.20
(dd, 1 H, pꢀH phenylimine, J = 7.3 Hz, J = 7.3 Hz); 7.28 (d,
1 H, H(6), J = 8.6 Hz); 7.39—7.41 (m, 3 H, 2 oꢀHPh + pꢀHPh);
7.46 (dd, 2 H, 2 mꢀH phenylimine, J = 7.9 Hz, J = 7.6 Hz);
7.49—7.51 (m, 2 H, 2 mꢀHPh); 8.14 (dd, 1 H, H(7), J = 8.9 Hz,
J = 2.1 Hz); 10.42 (d, 1 H, H(9), J = 2.1 Hz); 11.77 (s, 1 H, NH).
7ꢀMethylꢀ3ꢀphenylꢀ1ꢀphenyliminothiazolo[3,4ꢀa]quinoxalinꢀ
4(5H)ꢀone (5a), 8ꢀmethylꢀ3ꢀphenylꢀ1ꢀphenyliminothiazoloꢀ
[3,4ꢀa]quinoxalinꢀ4(5H)ꢀone (6a), 7ꢀmethylꢀ3ꢀphenylꢀ1ꢀ(thiazolꢀ
2ꢀyl)iminothiazolo[3,4ꢀa]quinoxalinꢀ4(5H)ꢀone (9b), and
8ꢀmethylꢀ3ꢀphenylꢀ1ꢀ(thiazolꢀ2ꢀyl)iminothiazolo[3,4ꢀa]quinoxꢀ
alinꢀ4(5H)ꢀone (9c) (a mixture of two pairs of isomers 5a, 6a and
9b, 9c in a percentage ratio of 5 : 2 : 65 : 28). A solution of
4ꢀhydroxythiazolidine 1b (0.5 g, 1.2 mmol) and 1,2ꢀdiaminoꢀ
4ꢀmethylbenzene (2c) (0.15 g, 1.2 mmol) in AcOH (30 mL) was
refluxed for 2 h. The yellow precipitate that formed was filtered
off. The mixture 5a + 6a + 9b + 9c was obtained in a yield of
0.21 g (45%), m.p. 327—335 °C. IR, ν/cm–1: 3200—2700 (NH),
1688 (C=O), 1605 (C=N), 1584, 1543. 1H NMR, δ: 2.31, 2.32,
2.34, and 2.40 (all s, 3 H each, Me); 6.96—7.64 (m, 38 H, 6 Ph,
4 H(6), 2 H(7), 2 H(8)); 7.33 (d, 1 H, H(5) or H(4) thiazole,
J = 3.7 Hz); 7.35 (d, 1 H, H(5) or H(4) thiazole, J = 3.7 Hz);
7.62 (d, 1 H, H(5) or H(4) thiazole, J = 3.7 Hz); 7.64 (d, 1 H,
H(5) or H(4) thiazole, J = 3.7 Hz); 9.27 (s, 1 H, H(9)); 9.29
(d, 1 H, H(9), J = 8.9 Hz); 9.52 (s, 1 H, H(9)); 9.55 (d, 1 H,
H(9), J = 8.4 Hz); 11.15, 11.18, 11.31, and 11.34 (all s, 1 H each,
NH). The mixture 5a + 6a + 9b + 9c was recrystallized from
DMF. Compound 9b was obtained in a yield of 0.12 g (25%)
as yellow crystals, m.p. >350 °C. Found (%): C, 61.15; H, 3.51;
N, 14.30; S, 16.22. C20H14N4OS2. Calculated (%): C, 61.52;
H, 3.61; N, 14.35; S, 16.40. IR, ν/cm–1: 3020—2819 (NH),
1
1688 (C=O), 1630, 1607, 1588, 1584, 1546. H NMR, δ: 2.24
and 2.30 (both s, 3 H each, Me); 6.97 (s, 1 H, H(6)); 7.32 (d,
1 H, H(5) or H(4) thiazole, J = 3.5 Hz); 7.42—7.44 (m, 3 H,
2 oꢀHPh + pꢀHPh); 7.56—7.58 (m, 2 H, 2 mꢀHPh); 7.61 (d, 1 H,
H(5) or H(4) thiazole, J = 3.5 Hz); 9.49 (s, 1 H, H(9)); 11.26 (s,
1 H, NH). Water (5 mL) was added to the filtrate in DMF. The
crystals that precipitated were filtered off, washed with water
(2×5 mL), and dried in air. Compound 3b was obtained in a
yield of 0.13 g (27%); m.p. and the spectroscopic characteristics
of this compound are identical to those of the product prepared
by the reaction of “symmetrical” 4ꢀhydroxythiazolidine 1a with
1,2ꢀdiaminoꢀ4,5ꢀdimethylbenzene (2b).
7ꢀMethylꢀ3ꢀphenylꢀ1ꢀphenyliminothiazolo[3,4ꢀa]quinoxalinꢀ
4(5H)ꢀone (5a) and 8ꢀmethylꢀ3ꢀphenylꢀ1ꢀphenyliminothiazoloꢀ
[3,4ꢀa]quinoxalinꢀ4(5H)ꢀone (6a) (a mixture of isomers 5a + 6a
in a percentage ratio of 61 : 39). A solution of 4ꢀhydroxyꢀ
thiazolidine 1a (1 g, 2.6 mmol) and 1,2ꢀdiaminoꢀ4ꢀmethylꢀ
benzene (2c) (0.31 g, 2.6 mmol) in AcOH (15 mL) was refluxed
for 3 h. The yellow crystals that precipitated were filtered off.
A mixture 5a + 6a was obtained in a yield of 0.85 g (85%),
m.p. 269—273 °C. IR, ν/cm–1: 3336—3028 (NH), 1671 (C=O),
1617 (C=N), 1514. 1H NMR, δ: 2.31 and 2.32 (both s, 3 H each,
Me); 6.96—7.48 (m, 24 H, 4 Ph, 2 H(6), H(7), H(8)); 9.28 (s,
1 H, H(9)); 9.29 (d, 1 H, H(9), J = 8.9 Hz); 11.15 and 11.18
(both s, 1 H each, NH). The isomers were separated by column
chromatography on silica gel Kieselgel (chloroform—hexane,
2 : 1, as the eluent); Rf are given for a stationary layer of silica gel
Silufol using a 1 : 3 : 2 chloroform—hexane—methanol system.
The yield of compound 5a was 0.41 g (48%), yellow crystals,
Rf 0.68, m.p. 280—283 °C. Found (%): C, 72.06; H, 4.44;
N, 10.97; S, 8.36. C23H17N3OS. Calculated (%): C, 71.86;
H, 4.14; N, 10.58; S, 8.29. IR, ν/cm–1: 3195—2871 (NH), 1674
(C=O), 1614 (C=N), 1587, 1575, 1520, 1485. 1H NMR, δ: 2.30
(s, 3 H, Me); 6.93—6.95 (m, 2 H, H(6), H(8)); 7.06 (d, 2 H,
2 oꢀH phenylimine, J = 7.6 Hz); 7.13 (dd, 1 H, pꢀH phenylimine,
J = 7.6 Hz, J = 7.1 Hz); 7.35—7.37 (m, 3 H, 2 oꢀHPh + pꢀHPh);
7.40 (dd, 2 H, 2 mꢀH phenylimine, J = 7.3 Hz, J = 7.3 Hz);
7.45—7.47 (m, 2 H, 2 mꢀHPh); 9.27 (d, 1 H, H(9), J = 8.9 Hz);
11.15 (s, 1 H, NH). The yield of compound 6a was 0.26 g (31%),
yellow crystals, Rf 0.56, m.p. 317—320 °C. Found (%): C, 72.00;
H, 4.42; N, 10.93; S, 8.34. C23H17N3OS. Calculated (%):
C, 71.86; H, 4.14; N, 10.58; S, 8.29. IR, ν/cm–1: 3180—2854
1
1689 (C=O), 1605 (C=N), 1582, 1542. H NMR, δ: 2.33 (s,
3 H, Me); 7.02 (s, 1 H, H(6)); 7.06 (d, 1 H, H(8), J = 8.6 Hz);
7.32 (d, 1 H, H(5) or H(4) thiazole, J = 3.6 Hz); 7.43—7.46
(m, 3 H, 2 oꢀHPh + pꢀHPh); 7.57—7.59 (m, 2 H, 2 mꢀHPh); 7.61
(d, 1 H, H(5) or H(4) thiazole, J = 3.7 Hz); 9.54 (d, 1 H, H(9),
J = 8.6 Hz); 11.33 (s, 1 H, NH).
1
(NH), 1671 (C=O), 1614 (C=N), 1587, 1513, 1488. H NMR,
δ: 2.31 (s, 3 H, Me); 7.02—7.04 (m, 2 H, H(6), H(8)); 7.07 (d,
2 H, 2 oꢀH phenylimine, J = 7.1 Hz); 7.14 (dd, 1 H, pꢀH
phenylimine, J = 7.1 Hz, J = 7.1 Hz); 7.33—7.35 (m, 3 H,
2 oꢀHPh + pꢀHPh); 7.42 (dd, 2 H, 2 mꢀH phenylimine,
J = 7.8 Hz, J = 7.1 Hz); 7.43—7.47 (m, 2 H, 2 mꢀHPh); 9.25
(s, 1 H, H(9)); 11.14 (s, 1 H, NH).
7ꢀNitroꢀ3ꢀphenylꢀ1ꢀphenyliminothiazolo[3,4ꢀa]quinoxalinꢀ
4(5H)ꢀone (5b) and 8ꢀnitroꢀ3ꢀphenylꢀ1ꢀphenyliminothiazoloꢀ
[3,4ꢀa]quinoxalinꢀ4(5H)ꢀone (6b) (a mixture of isomers 5b + 6b
in a percentage ratio of 11 : 89). A solution of 4ꢀhydroxyꢀ
thiazolidine 1a (1 g, 2.60 mmol) and 1,2ꢀdiaminoꢀ4ꢀnitrobenꢀ
zene (2d) (0.40 g, 2.60 mmol) in AcOH (15 mL) was refluxed for
6 h. The orange crystals that formed were filtered off. A mixture
5b + 6b was obtained in a yield of 0.76 g (74%), m.p. 320—326 °C.
8ꢀNitroꢀ3ꢀphenylꢀ1ꢀphenyliminothiazolo[3,4ꢀa]quinoxalinꢀ
4(5H)ꢀone (6b), 7ꢀnitroꢀ1ꢀ(thiazolꢀ2ꢀyl)iminoꢀ3ꢀphenylthiazoloꢀ
[3,4ꢀa]quinoxalinꢀ4(5H)ꢀone (9e), and 8ꢀnitroꢀ1ꢀ(thiazolꢀ
2ꢀyl)iminoꢀ3ꢀphenylthiazolo[3,4ꢀa]quinoxalinꢀ4(5H)ꢀone (9d)
(a mixture of 6b and a pair of isomers 9e and 9d in a percentage
ratio of 26 : 3 : 71). A mixture of 4ꢀhydroxythiazolidine 1b
(0.25 g, 0.6 mmol) and 1,2ꢀdiaminoꢀ4ꢀnitrobenzene (2d)
(0.09 g, 0.6 mmol) was refluxed in AcOH (20 mL) for 4 h. The
orange precipitate that formed was filtered off. A mixture
6b + 9e + 9d was obtained in a yield of 0.07 g (28%),
m.p. 324—332 °C. IR, ν/cm–1: 3276—2854 (NH), 1681 (C=O),
1
1605 (C=N), 1593, 1573, 1525, 1504. H NMR, δ: 7.11—7.59
(m, 20 H, 4 Ph); 7.25 (d, H(6), J = 8.9 Hz); 7.30 (d, H(6),

Thiazolo[3,4ꢀa]quinoxalines
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 1, January, 2009
201
J = 8.9 Hz); 7.38 (d, 1 H, H(5) or H(4) thiazole, J = 3.7 Hz);
7.41 (d, 1 H, H(5) or H(4) thiazole, J = 3.4 Hz); 7.63 (d, 1 H,
H(5) or H(4) thiazole, J = 3.7 Hz); 7.66 (d, 1 H, H(5) or H(4)
thiazole, J = 3.4 Hz); 7.97 (d, 1 H, H(6), J = 2.7 Hz); 8.11 (dd,
1 H, H(7), J = 8.9 Hz, J = 2.5 Hz); 8.07 (dd, H(8), J = 9.4 Hz,
J = 2.70 Hz); 8.18 (dd, 1 H, H(7), J = 8.9 Hz, J = 2.5 Hz); 9.84
(d, 1 H, H(9), J = 9.4 Hz); 10.39 (d, 1 H, H(9), J = 2.5 Hz);
10.69 (d, 1 H, H(9), J = 2.5 Hz); 11.65, 11.76, and 11.91 (all s,
1 H each, NH). The filtrate was concentrated, the residue was
treated with diethyl ether, and the precipitate was filtered off.
An additional amount of the mixture 6b + 9e + 9d was obtained
(0.05 g, 20%). The mixture 6b + 9e + 9d was recrystallized from
DMF. Compound 9d was obtained in a yield of 0.07 g (29%),
m.p. 342—343 °C. Found (%): C, 44.74; H, 2.04; N, 13.62;
S, 12.48. C19H11N5O3S•DMF. Calculated (%): C, 44.89; H,
2.17; N, 13.78; S, 12.60. IR, ν/cm–1: 3180—2852, 1698 (C=O),
1647, 1617, 1534. 1H NMR, δ: 7.36 (d, 1 H, H(6), J = 8.5 Hz);
7.42 (d, 1 H, H(5) or H(4) thiazole, J = 3.6 Hz); 7.48—7.50 (m,
3 H, 2 oꢀHPh + pꢀHPh); 7.61—7.63 (m, 2 H, 2 mꢀHPh); 7.68 (d,
1 H, H(5) or H(4) thiazole, J = 3.6 Hz); 8.24 (dd, 1 H, H(7),
J = 8.5 Hz, J = 2.5 Hz); 10.75 (d, 1 H, H(9), J = 2.5 Hz); 11.95
(s, 1 H, NH).
Kazan Research Center of the Russian Academy of Sciences.
The crystallographic characteristics and the Xꢀray data collecꢀ
tion and refinement statistics are given in Table 2. The Xꢀray
diffraction data were collected on an automated fourꢀcircle
CADꢀ4 NONIUS B.V. diffractometer (graphite monochromaꢀ
tor, CuꢀКα radiation) at 20 °C. The Xꢀray data were processed
with the use of the MolEN program29 on an AlphaStation 200.
The intensities of three check reflections showed no decrease in
the course of Xꢀray data collection. The empirical absorption
correction was applied. All structures were solved by direct
methods with the use of the SIR program30 and refined first
isotropically and then anisotropically using the SHELXLꢀ9731
and WinGX32 program packages. The coordinates of the hydroꢀ
gen atoms of the amino groups were located in difference elecꢀ
tron density maps (the coordinates of the other hydrogen atoms
were calculated based on the stereochemical criteria) and
refined using a riding model. The intermolecular interactions
were analyzed and the figures were drawn with the use of the
PLATON program.25 The atomic coordinates and displacement
parameters for compounds 3b and 9d were deposited with the
Cambridge Structural Database (http://www.ccdc.cam.ac.uk;
CCDC 671888 and 671887, respectively).
Singleꢀcrystal Xꢀray diffraction study of compounds 3b
and 9d was carried out at the Department of Xꢀray Diffraction
Studies of the Center of Collaborative Research on the basis
of the Laboratory of Xꢀray Diffraction Methods of the
A. E. Arbuzov Institute of Organic and Physical Chemistry, the
This study was financially supported by the Russian
Foundation for Basic Research (Project Nos 07ꢀ03ꢀ00613ꢀa
and 05ꢀ03ꢀ33008ꢀa), the Council on Grants of the President
of the Russian Federation (Program for State Support of
Leading Scientific Schools, Grant NShꢀ3758.2008.3), and
the Federal Target Program “Research and Development
in Priority Fields of Science and Technology in Russia in
2007—2012” (State Contract No. 02.512.11.2237).
Table 2. Crystallographic characteristics and the Xꢀray data colꢀ
lection and refinement statistics for compounds 3b and 9d
Parameter
3b
9d
Color and shape
Molecular formula
Yellow, prismatic shape
C24H19N3OS• C19H11N5O3S2•
References
•C2H6OS
475.61
Monoclinic
P21/n
8.530(1)
9.379(1)
29.260(6)
90
91.70(1)
90
2339.9(6)
4
•C3H7NO
494.54
Tric–linic
P1
7.0160(6)
12.718(1)
13.772(1)
72.283(9)
87.253(8)
73.644(9)
1122.25(17)
2
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Received June 3, 2008;
in revised form September 22, 2008