Fused polycyclic nitrogen-containing heterocycles 11. 4-Hydroxy-3,5- diphenyl-2-phenyliminothiazolidines as new key compounds in the synthesis of thiazolo[3,4-a]quinoxaline derivatives

Article abstract of DOI:10.1007/s11172-005-0156-0

A procedure was developed for the synthesis of thiazolo[3,4-a]quinoxaline derivatives based on a new strategy for construction of the pyrazine ring. The key step of the process involves the reaction of 4-hydroxy-3,5-diphenyl-2- phenyliminothiazolidines with o-phenylenediamines.

Full text of DOI:10.1007/s11172-005-0156-0

2568
Russian Chemical Bulletin, International Edition, Vol. 53, No. 11, pp. 2568—2576, November, 2004
Fused polycyclic nitrogenꢀcontaining heterocycles
11.* 4ꢀHydroxyꢀ3,5ꢀdiphenylꢀ2ꢀphenyliminothiazolidines as
new key compounds in the synthesis of thiazolo[3,4ꢀa]quinoxaline derivatives
a
b
a
V. A. Mamedov,a I. Z. Nurkhametova, S. K. Kotovskaya, A. T. Gubaidullin,
ꢀ
Ya. A. Levin,a I. A. Litvinov,a and V. N. Charushinc
aA. 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.kcn.ru
bUrals State Technical University,
19 ul. Mira, 620002 Ekaterinburg, Russian Federation.
Fax: +7 (343 2) 74 0458. Eꢀmail: charushin@htf.ustu.ru
cI. Ya. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences,
20 ul. S. Kovalevskoi, 620219 Ekaterinburg, Russian Federation.
Fax: +7 (343 2) 74 0458. Eꢀmail: charushin@prm.ustu.ru
A procedure was developed for the synthesis of thiazolo[3,4ꢀa]quinoxaline derivatives
based on a new strategy for construction of the pyrazine ring. The key step of the process
involves the reaction of 4ꢀhydroxyꢀ3,5ꢀdiphenylꢀ2ꢀphenyliminothiazolidines with oꢀphenyleneꢀ
diamines.
Key words: Hantzsch reaction, Bodroux reaction, Phillips reaction, 4ꢀhydroxythiazolidines,
thiazolo[3,4ꢀa]quinoxalines, Xꢀray diffraction study.
Compounds of the diazine series belong to an imporꢀ
cessible Nꢀ2ꢀnitrophenylꢀ and Nꢀ2,4ꢀdinitrophenylꢀ
thiazolidineꢀ4ꢀcarboxylic acids.8
tant class of biologically active heterocycles. Fused polyꢀ
cyclic heterocycles containing the 1,4ꢀdiazine fragment,
such as folic acid, riboflavin, tetrahydrobiopterin, or xanꢀ
thopterin, are vitally important.2 Quinoxaline derivatives
possess a wide spectrum of biological activities, such as
antibacterial, antitumor, and antiviral activities, includꢀ
ing antiꢀHIV activity.3,4
The main synthetic approaches to quinoxalines and
other fused pyrazines are described in the literature.5,6
Among various cyclizations giving rise to fused azaꢀ
heterocycles, the reactions of compounds containing two
nucleophilic groups with bifunctional electrophilic reꢀ
agents are of particular importance. Condensation of
dicarbonyl compounds with 1,2ꢀdiaminoazines7 is a
prominent example.
The synthetic potential of 4ꢀhydroxythiazolidines,
which are unstable intermediates in the synthesis of thiazꢀ
oles by the Hantzsch reaction, has remained unexꢀ
plored.9,10 Earlier,11,12 we have demonstrated that the
reaction of methyl chloro(phenyl)pyruvate with N,N´ꢀdiꢀ
phenylthiourea affords an abnormally stable intermediate
of the Hantzsch reaction, viz., 4ꢀhydroxyꢀ4ꢀmethoxyꢀ
carbonylꢀ3,5ꢀdiphenylꢀ2ꢀphenyliminothiazolidine (1a),
Scheme 1
In the present study, we developed a new convenient
procedure for the synthesis of thiazolo[3,4ꢀa]quinoxaline
derivatives involving condensation of potential αꢀdiꢀ
carbonyl compounds, viz., 4ꢀhydroxyꢀ3,5ꢀdiphenylꢀ2ꢀ
phenyliminothiazolidines, with oꢀphenylenediamine deꢀ
rivatives. A known method for the synthesis of thiazoꢀ
lo[3,4ꢀa]quinoxalines involves reduction of difficultly acꢀ
* For Part 10, see Ref. 1.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2462—2470, November, 2004.
1066ꢀ5285/04/5311ꢀ2568 © 2004 Springer Science+Business Media, Inc.

Polycyclic nitrogenꢀcontaining heterocycles
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 11, November, 2004 2569
Scheme 3
which is dehydrated only by strong dehydrating agents,
such as polyphosphoric acid (PPA) or SOCl2 (Scheme 1).
According to our data,12 hydroxythiazolidine 1a exists
in solution as a mixture of diastereomers αꢀ1a and βꢀ1a,
which are in equilibrium via openꢀchain isothioureido
structure 3a (Scheme 2). However, we failed to detect the
latter by various spectroscopic methods.
Scheme 2
R = H (а), F (b)
With the aim of examining the scope of this unexꢀ
pected reaction and preparing fluorinated thiazoloꢀ
quinoxaline (5b), we carried out the reaction of hydroxyꢀ
thiazolidine 1a with 4,5ꢀdifluoroꢀ1,2ꢀphenylenediꢀ
amine (4b).15 Since the nitrogen atoms in this diamine
have low nucleophilicity due to the presence of strong
electronꢀwithdrawing fluorine atoms, the reaction of this
compound proceeds much more slowly (under the aboveꢀ
described conditions, the reaction is completed in 8 h) to
give compound 5b. The structure of the latter was conꢀ
1
firmed by the presence, in its H NMR spectrum, of a
signal for the H(9) proton as a doublet of doublets with
the coupling constants 3JH,F = 13.9 Hz and 4JH,F = 8.4 Hz
along with other multiplets at δ 7.36—7.48 belonging to
eleven protons (protons of two phenyl groups and the
H(6) proton) and a singlet for the proton of the NH group
at δ 11.21.
Earlier,13,14 we have found that treatment of comꢀ
pound 1a with oꢀphenylenediamine (4a) in refluxing
AcOH readily results in condensation to give 4,5ꢀdihydroꢀ
3ꢀphenylꢀ1ꢀphenyliminothiazolo[3,4ꢀa]quinoxalinꢀ4ꢀone
(5a) (Scheme 3).
The structure of compound 5b was confirmed also by
Xꢀray diffraction analysis (Fig. 1). Compound 5b crystalꢀ
C(14)
C(15)
C(13)
C(25)
C(16)
C(12)
C(17)
C(24)
N(11)
S(2)
C(1)
C(19)
C(22)
C(20)
S(1)
C(18)
O(1)
N(10)
C(9)
C(21)
C(3)
C(3A)
C(9A)
C(23)
C(8)
F(8)
C(4)
C(7)
O(4)
C(5A)
N(5)
F(7)
C(6)
Fig. 1. Molecular structure of compound 5b.

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Russ.Chem.Bull., Int.Ed., Vol. 53, No. 11, November, 2004
Mamedov et al.
lizes as the 1 : 1 solvate with DMSO in the monoclinic
system, the DMSO molecule in the crystal being disorꢀ
dered over two positions with occupancies of 0.7 and 0.3.
It should be noted that the thiazoloquinoxaline ring in
compound 5b, as in analogous compounds studied earꢀ
lier,14 is planar (to within 0.03(3) Å). The phenyl substituꢀ
ents (C(12)—C(17) and C(18)—C(23)) are twisted with
respect to the plane of the thiazoloquinoxaline moiety by
81.3° and 51.2°, respectively. Of intramolecular contacts,
the C—H...N interaction involving the H(9) proton of the
phenyl substituent and the N(11) atom (d(H(9)...N(11)),
2.19 Å; ∠(C(9)—H(9)...N(11)), 127°) is noteworthy. Earꢀ
lier, we have demonstrated that such systems are characꢀ
terized by the formation of dimers through classical hyꢀ
drogen bonds, provided that the crystal contains no solꢀ
vate molecules. The presence of solvates prevents the forꢀ
mation of dimers but favors a great diversity of intermoꢀ
lecular contacts.16 Analysis of intermolecular interactions
in the crystal of compound 5b confirms the earlier obserꢀ
vation. The molecules of this compound do not form
dimers in the crystal (Fig. 2); each molecule is involved in
contacts with two solvate molecules as a donor (through
the bifurcated hydrogen bond, viz., N(5)—H(5)...S(1)
and N(5)—H(5)...O(1); d(H(5)...S(1)), 2.87 Å;
∠(N(5)—H(5)...S(1)), 154°; d(H(5)...O(1)), 1.94 Å;
∠(N(5)—H(5)...O(1)), 175°) and an acceptor (through
the C(24)—H(243)...O(4´) interaction; the symmetry
operation (–1 + x, y, z); d(H(243)...O(4´)), 2.57 Å;
∠(C(24)—H(243)...O(4´)), 152°). There are also strong
π—π contacts in the crystal. Interaction of the electronic
systems of the benzoquinoxaline fragments of the molꢀ
ecules related to each other by the symmetry operation
(1 – x, 1 – y, –z) results in the formation of πꢀdimers (the
shortest distance between the planes of the rings is
3.39(2) Å, the dihedral angle is 0°). Each molecule of the
πꢀdimer is involved in C—H...S contacts (d(H(15)...S(2´)),
2.86 Å; ∠(C(15)—H(15)...S(2´)), 175°; the symmetry opꢀ
eration (1/2 – x, –1/2 + y, 1/2 – z)) with the molecules of
the adjacent πꢀdimers, whose tricyclic fragments are
twisted by 90°. Due to the involvement of DMSO molꢀ
ecules in the contacts, these chains of the molecules, which
are linked through alternating π—π and C—H...S conꢀ
tacts, form a network of hydrogenꢀbonded molecules. The
presence of disordered DMSO molecules indicates that
the crystal contains cavities. This is also evidenced by a
rather low packing coefficient of the molecules (0.67). In
the crystal, hydrophobic and hydrophilic regions are loꢀ
calized, viz., the phenyl substituents possessing hydroꢀ
phobic properties form pseudolayers alternating with layꢀ
ers containing the hydrophilic tricyclic fragments of molꢀ
ecules 5b and DMSO.
As regards the mechanism of the reaction of hydroxyꢀ
thiazolidine 1a with 1,2ꢀphenylenediamines, both linear
and cyclic tautomers can give the same intermediate A,
from which the final products 5a,b are formed (Scheme 4).
Each of the possible reaction pathways, viz., amidation
(path a), amination (path b), or imination (path c), inꢀ
volves various types of electrophilic substitution at the
nitrogen atom of the amino group of oꢀphenylenediamines
as the first step.
To elucidate which reaction route to thiazoꢀ
lo[3,4ꢀa]quinoxalines 5 is preferable, we performed the
Fig. 2. Fragment of a hydrogen bond network in the crystal of thiazolo[3,4ꢀa]quinoxaline 5b. Only the protons involved in hydrogen
bonding (dashed lines) are shown.

Polycyclic nitrogenꢀcontaining heterocycles
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 11, November, 2004 2571
reaction of 4ꢀhydroxythiazolidine 1a with 4ꢀnitroꢀ1,2ꢀ
phenylenediamine (4c). Depending on the reaction path,
this reaction could give isomeric final products 5c (path a)
or 5d (paths b and c), which differ in the position of the
nitro group (Schemes 5—7).
The fact that the reaction with 4ꢀnitroꢀ1,2ꢀphenyleneꢀ
diamine (4c) affords only one product is evidenced by the
identity of the 1H NMR spectra of the crude product and
the product following recrystallization from DMF (the
latter spectrum contains additional signals corresponding
to the solvent because of the formation of a crystal solꢀ
vate). However, it is impossible to differentiate the strucꢀ
tures 5c and 5d based only on the 1H NMR spectroscopic
data. The formation of 4,5ꢀdihydroꢀ8ꢀnitroꢀ3ꢀphenylꢀ1ꢀ
phenyliminothiazolo[3,4ꢀa]quinoxalinꢀ4ꢀone (5d) was
confirmed by Xꢀray diffraction analysis (Fig. 3). Comꢀ
pound 5d, like compound 5b, crystallizes in the monoꢀ
clinic system as a 1 : 1 solvate with DMF. The unit cell
parameters of 5d are similar to those of compound 5b.
The differences in the structure of the carbocyclic moiety
of compounds 5b and 5d do not change substantially the
geometry and the bond length distribution in the tricyclic
fragment of the molecule. Even the twist angles of the
phenyl substituents relative to the plane of the tricyclic
Scheme 4
Scheme 5

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Russ.Chem.Bull., Int.Ed., Vol. 53, No. 11, November, 2004
Mamedov et al.
Scheme 6
Scheme 7
vent and the presence of the nitro group lead to a substanꢀ
tial change in the system of intermolecular contacts and
the resulting supramolecular structure. The molecular and
crystal structures of substituted thiazoloquinoxalines, inꢀ
cluding compound 5d, will be described in more detail
elsewhere.
Therefore, if the hypothesis that the primary reaction
involves only the 2ꢀamino group of 4ꢀnitroꢀ1,2ꢀpheꢀ
nylenediamine (4c) is correct, the fact that the reaction
affords exclusively compound 5d rules out the possibility
of the path a (see Scheme 5). This assumption holds
apparently also for other 1,2ꢀphenylenediamines. Actuꢀ
ally, amidation of weakly basic arylamines 4 (path a) seems
to be less rapid and, correspondingly, less competitive
compared to the formation of azomethine (path c). Moreꢀ
over, acylation of arylamines with esters generally reꢀ
quires basic catalysis, for example, under conditions of
metallation of the amino group in the Bodroux reaction.17
This method was used for the acylation of 1,2ꢀphenyleneꢀ
diamine (4a) with esters.18 Moreover, 2ꢀsubstituted benzꢀ
imidazoles should easily be prepared (the Phillips reacꢀ
tion)19 from the initially formed oꢀaminoacylanilides B
(path a) under acidic conditions used in the reaction of
1,2ꢀphenylenediamines (4) with hydroxythiazolidine 1a.
However, in no case were 2ꢀsubstituted benzimidazoles
detected among the reactions products of comꢀ
pounds 1 and 4.
fragment in 5d (51.2° and 81.3°) are rather similar to
those observed in compound 5b (57.8° and 72.0°). The
presence of the DMF solvate molecules in the crystal of
compound 5d also prevents the formation of hydrogenꢀ
bonded dimers of 5d. However, another type of the solꢀ
Of the other reaction routes to 8ꢀnitrothiazoꢀ
lo[3,4ꢀa]quinoxaline (5d), the path c, which proceeds via
openꢀchain tautomer 3a and the intermediate imine F
(see Scheme 7), rather than the path b, which proceeds
via the amine C (see Scheme 6), seems to be the most
probable, because the formation of the structure C reꢀ
quires the unfavorable nucleophilic substitution of the
hydroxy group at the sterically hindered carbon atom C(4).
Only one product was obtained in good yield in the
reaction of 4ꢀhydroxythiazolidine 1a with 4ꢀmethylꢀ1,2ꢀ
Fig. 3. Molecular structure of compound 5d.

Polycyclic nitrogenꢀcontaining heterocycles
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 11, November, 2004 2573
Scheme 9
phenylenediamine (4d) (Scheme 8). Taking into account
that the substituent has the major effect on the reactivity
of the pꢀamino group in diamine 4d, we assigned the
structure of 4,5ꢀdihydroꢀ7ꢀmethylꢀ3ꢀphenylꢀ1ꢀphenylꢀ
iminothiazolo[3,4ꢀa]quinoxalinꢀ4ꢀone (5e) to this prodꢀ
uct. Actually, the 1H NMR spectrum shows singlets of the
methyl and carbamoyl groups and a multiplet for 12 proꢀ
tons (protons of two phenyl rings and two protons of the
benzene ring) along with a signal for the third proton of
this fragment, viz., a diagnostic doublet for the H(9) proꢀ
ton at δ 9.27 with the vicinal coupling constant 3J =
8.9 Hz. This fact indicates that the methyl group is bound
to the C(7) atom (compound 5e) rather than to C(8)
(compound 5e´), because in the latter case the signal for
the H(9) proton would appear as a singlet or a doublet
4
with a very small constant J.20—23 This conclusion was
confirmed by Xꢀray diffraction analysis.
Scheme 8
Scheme 10
4ꢀHydroxythiazolidines (1b—d), which were syntheꢀ
sized from nonsymmetrical thiourea derivatives, viz.,
NꢀphenylꢀN´ꢀtolylꢀ,24 N´ꢀ2ꢀnaphthylꢀNꢀphenylꢀ,24 and
NꢀphenylꢀN´ꢀ(thiazolꢀ2ꢀyl)thioureas,25 react with
1,2ꢀphenylenediamine (4a) analogously to 4ꢀhydroxyꢀ
thiazolidine 1a, which was prepared from symmetriꢀ
cal N,N´ꢀdiphenylthiourea. In the general case, these
hydroxythiazolidines exist as tautomeric mixtures
1b—d+1b´—d´+3b—d (Scheme 9).
Judging from the IR and 1H NMR spectroscopic data,
the component ratio for these mixtures depends substanꢀ
tially on the nature of the substituent R and the condiꢀ
tions of isolation and purification of the samples. The
regioꢀ and diastereomeric compositions of these mixtures
are beyond the scope of the present study. Let us only
note that the IR spectrum of the condensation product of
NꢀphenylꢀN´ꢀ(thiazolꢀ2ꢀyl)thiourea has a highꢀintensity
absorption band of the keto group at 1764 cm–1, which
provides evidence that the mixture contained predomiꢀ
nantly tautomer 3d. Condensation of both cyclic and
openꢀchain tautomers with oꢀphenylenediamine (4a) afꢀ
Initial
tautomeric
mixture
1,2ꢀPhenyleneꢀ Composition*
Preparative
yield (%)
diamine
of product (%)
1b+3b+1b´
1c+3c+1c´
1d+3d+1d´
1d+3d+1d´
4a
4a
4a
4b
5a (8)
5a (34) 5g (66)
5a (4)
5b (0)
5f (92)
5a (5)
5f (86)
5a (28) 5g (61)
5h (96)
5i (100)
5a (0)
5b (0)
5h (94)
5i (96)
* Calculated from the integral intensities of the peaks of the
H(9) protons in the 1H NMR spectra of crude products.

2574
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 11, November, 2004
Mamedov et al.
dried with MgSO4, the solution was concentrated, and the resiꢀ
due was recrystallized from PriOH. The yield of 1b+1b´ mixture
was 3.84 g (92%). M.p. 171—174 °C. Found (%): C, 68.62;
H, 5.31; N, 6.83; S, 7.45. C24H22N2O3S. Calculated (%):
C, 68.96; H, 5.26; N, 6.70; S, 7.67. IR, ν/cm–1: 3520, 3500
fords mixtures of thiazolo[3,4ꢀa]quinoxalines 5a and 5f—h
(Scheme 10). The differences in solubility of the compoꢀ
nents of these pairs allows one to separated them by fracꢀ
tional crystallization.
The ratio of thiazoloquinoxalines in the resulting mixꢀ
ture depends on the ease of elimination of PhNH2 or
RNH2 from the same intermediate G. Condensation of
fluorineꢀcontaining 1,2ꢀphenylenediamine 4b with a tauꢀ
tomeric mixture 1d+3d+1d´ did not afford compound 5b.
1
(OH); 3100—3000 (NH); 1735 (C=O); 1640 (C=N). H NMR
(DMFꢀd7), δ: 3.27 and 3.29 (both s, 3 H each, Me); 3.66 and
3.69 (both s, 3 H each, OMe); 5.47 and 5.48 (both s, 1 H each,
CH); 6.50 (br.s, 2 H, 2 OH); 6.82—7.33 (m, 14 H, Ph, C6H4).
4ꢀHydroxyꢀ4ꢀmethoxycarbonylꢀ3ꢀ(2ꢀnaphthyl)ꢀ5ꢀphenylꢀ2ꢀ
phenyliminothiazolidine (1c) and 4ꢀhydroxyꢀ4ꢀmethoxycarbonylꢀ
3,5ꢀdiphenylꢀ2ꢀ(2ꢀnaphthylimino)thiazolidine (1c´) were prepared
analogously from Nꢀ(2ꢀnaphthyl)ꢀN´ꢀphenylthiourea. The yield
was 89%, m.p. 173—176 °C. Found (%): C, 71.05; H, 5.24;
N, 6.46; S, 6.97. C27H22N2O3S. Calculated (%): C, 71.43;
H, 4.85; N, 6.17; S, 7.06. IR, ν/cm–1: 3505 (OH); 3120—3000
(NH); 1740 (C=O); 1630 (C=N). 1H NMR (DMFꢀd7), δ: 3.67
(s, 3 H, OMe); 5.47 (s, 1 H, CH); 7.02—7.96 (m, 18 H,
Ph, C10H7, OH).
Experimental
The 1H NMR spectra were recorded on a BrukerꢀMCLꢀ250
spectrometer operating at 250.13 MHz. The 13C NMR specꢀ
trum of compound 5a was measured on a Bruker MSLꢀ400
spectrometer operating at 100.61 MHz. The chemical shifts are
given in the δ scale being measured relative to DMSOꢀd6. The
IR spectra were recorded on a URꢀ20 spectrometer as Nujol
mulls. The melting points were determined on a Boetius hotꢀ
stage apparatus. The yields, melting points, elemental analysis
data, and spectroscopic characteristics of thiazoloquinoxalines
are given in Tables 1 and 2.
4ꢀHydroxyꢀ4ꢀmethoxycarbonylꢀ3,5ꢀdiphenylꢀ2ꢀphenyliminoꢀ
thiazolidine (1a) was prepared according to a known procedure.10
4ꢀHydroxyꢀ4ꢀmethoxycarbonylꢀ5ꢀphenylꢀ2ꢀphenyliminoꢀ3ꢀ
(4ꢀtolyl)thiazolidine (1b) and 4ꢀhydroxyꢀ4ꢀmethoxycarbonylꢀ3,5ꢀ
diphenylꢀ2ꢀ(4ꢀtolylimino)thiazolidine (1b´). Sodium acetate
(4.1 g, 0.05 mol) was added to a solution of NꢀphenylꢀN´ꢀpꢀ
tolylthiourea (4.84 g, 0.02 mol) in CH2Cl2 (100 mL). The reacꢀ
tion mixture was cooled to a temperature from –15 to –20 °C
and then methyl chloro(phenyl)pyruvate26 (4.2 g, 0.02 mol) was
carefully added. The reaction mixture was stirred for 3 h, allowꢀ
ing it to gradually warm to room temperature, and then poured
into water. The organic layer was separated and the aqueous
layer was extracted with CH2Cl2 (3×50 mL). The extract was
Sꢀ(αꢀMethoxalylbenzyl)ꢀNꢀphenylꢀN´ꢀ(thiazolꢀ2ꢀyl)isothioꢀ
urea (3d) was prepared analogously from NꢀphenylꢀN´ꢀ(thiazolꢀ
2ꢀyl)thiourea. The yield was 83%, m.p. 99—101 °C. Found (%):
C, 58.18; H, 3.95; N, 10.56; S, 15.82. C20H17N3O3S2. Calcuꢀ
lated (%): C, 58.44; H, 4.14; N, 10.22; S, 15.60. IR, ν/cm–1
:
3500—3000 (NH); 1764 (C=O); 1740 (C=O); 1630 (C=N).
1H NMR (DMSOꢀd6), δ: 3.64, 3.73, and 3.87 (all s (1 : 1 : 1.4),
3 H each, OMe); 5.22, 5.51, and 5.61 (all s, 1 H each, CH);
6.90—7.33 (m, Ph, C4SH3, NH, OH).
7,8ꢀDifluoroꢀ4,5ꢀdihydroꢀ3ꢀphenylꢀ1ꢀphenyliminothiazoꢀ
lo[3,4ꢀa]quinoxalinꢀ4ꢀone (5b). A solution of 4ꢀhydroxythiazolꢀ
idine 1a (2.02 g, 5 mmol) and 4,5ꢀdifluoroꢀ1,2ꢀphenylenediꢀ
amine (4b) (0.72 g, 5 mmol) in AcOH (25 mL) was refluxed
for 8 h. Cooling of the reaction mixture for 3 h afforded crystals,
which were filtered off to give analytically pure compound 5b in
a yield of 1.44 g. The filtrate was concentrated in vacuo to isolate
additionally yellow crystals of 5b in a yield of 0.32 g. The presꢀ
Table 1. Yields, melting points, and elemental analysis data for 1ꢀaryliminoꢀ4,5ꢀdihydroꢀ3ꢀ
phenylthiazolo[3,4ꢀa]quinoxalinꢀ4ꢀones (5a,b,d—i)
Comꢀ Yield
pound (%)
M.p./°C
(solvent)
Found
Calculated
Molecular
formula
(%)
C
H
N
S
5a
5b
5d
5e
5f
95
87
89
86
94
80
76
96
301—301.5
(DMSO)
296—297
(DMF)
343—344
(DMF)
69.50
69.87
65.17
65.24
61.61
61.77
72.06
71.86
72.06
71.87
74.81
74.46
60.61
60.64
55.21
55.34
5.06
4.89
3.13
3.21
4.31
4.38
4.44
4.14
4.44
4.16
3.21
4.06
3.25
3.19
2.35
2.43
10.11
15.45
15.40
8.07
7.92
6.58
6.73
8.36
8.29
8.36
8.19
7.71
7.64
17.41
17.02
15.73
15.55
C22H15N3OS•
Me2SO
C22H13F2N3OS
10.46
10.43
10.37
14.36
14.53
10.97
10.58
10.97
11.12
9.87
10.02
14.50
14.89
13.42
13.58
C22H14N4O3S•
HCONMe2
C23H17N3OS
275—277
(DMF)
257—259
(DMSO)
265—270
(AcOH)
345—345.5
(AcOH)
292—293
(MeCN)
C23H17N3OS
C26H17N3OS
C19H12N4OS2
C19H10F2N4OS2
5g
5h
5i

Polycyclic nitrogenꢀcontaining heterocycles
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 11, November, 2004 2575
Table 2. IR and 1H NMR spectra of 1ꢀaryliminoꢀ4,5ꢀdihydroꢀ3ꢀphenylthiazolo[3,4ꢀa]quinoxalinꢀ4ꢀones (5a,b,d—i)
Comꢀ
pound
IR,
ν/cm–1
1H NMR (DMSOꢀd6), δ, J/Hz
5a*
5b
3200—2700 (NH);
1680 (C=O); 1620 (C=N)
3250—2700 (NH);
1677 (C=O); 1619 (C=N)
3250—2600 (NH);
7.00—7.46 (m, 13 H, 2 Ph, H(6), H(7), H(8)); 9.39 (d, 1 H, H(9), J = 7.4);
11.13 (br.s, 1 H, NH)
7.36—7.48 (m, 11 H, 2 Ph, H(6)); 9.55 (dd, 1 H, H(9), J = 13.9, 8.4);
11.21 (s, 1 H, NH)
7.21—7.62 (m, 11 H, 2 Ph, H(6)); 8.18 (dd, 1 H, H(7), J = 8.9, 2.3);
10.50 (d, 1 H, H(9), J = 2.3); 11.69 (br.s, 1 H, NH)
5d
1680 (C=O); 1630 (C=N);
1210 (N=O)
5e
5f
3230—2600 (NH);
1665 (C=O); 1615 (C=N)
3220—2700 (NH);
1685 (C=O); 1635 (C=N)
3250—2550 (NH);
1670 (C=O); 1625 (C=N)
2.40 (s, 3 H, Me); 7.02—7.59 (m, 12 H, 2 Ph, H(7), Н(8)); 9.38 (d, 1 Н, H(9), J = 8.9);
11.06 (br.s, 1 H, NH)
2.38 (s, 3 H, Me); 7.05—7.59 (m, 12 H, Ph, C6H4, H(6), H(7), H(8)); 9.37 (d, 1 H, H(9),
J = 7.7); 11.12 (br.s,1 H, NH)
7.07—7.54 (m, 12 H, Ph, 4 H of naphthyl, H(6), H(7), H(8)); 7.70 (d, 1 H, H of naphthyl,
J = 8.1); 7.93 (d, 1 H, H of naphthyl, J = 7.3); 8.09 (d, 1 H, H of naphthyl, J = 8.1);
9.60 (d, 1 H, H(9), J = 8.1); 11.10 (br.s, 1 H, NH)
5g
5h**
3220—2600 (NH);
1685 (C=O); 1610 (C=N)
7.08—7.20 (m, 3 H, H(6), H(7), H(8)); 7.13 (d, 1 H, H(5) or H(4) of thiazole, J = 3.7);
7.28—7.33 (m, 3 H, 2 mꢀHPh, pꢀHPh); 7.47 (d, 1 H, H(4) or H(5) of thiazole, J = 3.7);
7.78 (d, 2 H, 2 oꢀHPh, J = 6.5); 8.50 (d, 1 H, H(9), J = 7.4); 10.83 (br.s, 1 H, NH)
7.04 (dd, 1 H, H(6), 3JHF = 10.5, 4JHF = 9.2); 7.11 (d, 1 H, H(5) or H(4) of thiazole,
J = 3.7); 7.25—7.32 (m, 3 H, 2 mꢀHPh, pꢀHPh); 7.46 (d, 1 H, H(4) or H(5) of thiazole,
J = 3.7); 7.74—7.76 (m, 2 H, 2 oꢀHPh); 8.53 (dd, 1 H, H(9), 3JH,F = 13.1, 4JH,F = 8.3);
10.89 (br.s, 1 H, NH)
5i*** 3278, 3250—2700 (NH);
1697 (C=O); 1632 (C=N)
*
13C NMR (100.6 MHz) of compound 5a (DMSOꢀd6), δ: 115.61 (dd, C(6) or C(9), J = 162.7 and 8.0 Hz); 118.43 (br.s, C(7) or C(8),
J = 167.6 Hz); 121.93 (t, C(3a), J = 4.6 Hz); 122.50 (br.s, C(3)); 122.82 (br.s, C(8) or C(7), J = 160.0 Hz); 125.70 (dd, C(9) or C(6),
J = 163.2 and 8.4 Hz); 126.21 (m, C(5a) or C(9a)); 131.42 (s, C(9a) or C(5a)); 153.25 (s, C=O); 154.60 (s, C=N); Ph: 121.17 (dt,
oꢀC, J = 158.5 and 7.9 Hz); 124.51 (dt, pꢀC, J = 164.4 and 7.1 Hz); 125.46 (br.s, ipsoꢀC); 128.16 (d, br.d, mꢀC, J = 159.9 and 7.3 Hz);
129.07 (dt, pꢀC, J = 160.9 and 6.3 Hz); 130.39 (dd, mꢀC, J = 158.8 and 8.1 Hz); 130.58 (dt, oꢀC, J = 161.3 and 8.1 Hz); 151.25 (t, CN,
J = 8.4 Hz).
1
** The H NMR spectrum was recorded in DMFꢀd7—CDCl3 (1 : 1).
*** The 1H NMR spectrum was recorded in DMFꢀd7.
ence of aniline in the filtrate was established by its transformaꢀ
tion into Nꢀbenzylideneaniline, m.p. 51—53 °C.
a = 8.823(5), b = 8.962(8), c = 28.587(6) Å, β = 90.04(2)°,
V = 2260(2) Å3, Z = 4, dcalc = 1.42 g cm–3, space group P21/n.
The unit cell parameters and the intensities of 2785 reflections,
of which 1109 reflections were with I ≥ 2σ, were measured at
20 °C (λ(CuꢀKα), graphite monochromator, ω/2θ scanning techꢀ
nique, θ ≤ 58.9°). The intensities of three check reflections
showed no decrease in the course of Xꢀray data collection. Abꢀ
sorption was ignored (µCu 2.52 cm–1). The structure was solved
by direct methods using the SIR program27 and refined first
isotropically and then anisotropically using the SHELXLꢀ97 28
and WINGX 29 program packages. Subsequently, the positions
of the hydrogen atoms were revealed from difference electron
density maps. The contributions of the hydrogen atoms to the
structure amplitudes were taken into account with fixed posiꢀ
tional and thermal parameters. The final reliability factors were
as follows: R = 0.075 and Rw = 0.128 based on 1109 reflections
with F 2 ≥ 4σ. The figures were drawn and intermolecular contacts
in the crystals were calculated using the PLATON program.30
The Xꢀray diffraction data for compound 5d were deposited
with the Cambridge Structural Database (CCDC No. 181760).*
4,5ꢀDihydroꢀ8ꢀnitroꢀ3ꢀphenylꢀ1ꢀphenyliminothiazoꢀ
lo[3,4ꢀa]quinoxalinꢀ4ꢀone (5d) and 4,5ꢀdihydroꢀ7ꢀmethylꢀ3ꢀpheꢀ
nylꢀ1ꢀphenyliminothiazolo[3,4ꢀa]quinoxalinꢀ4ꢀone (5e) were preꢀ
pared analogously by the reactions of 4ꢀnitroꢀ (4c) and 4ꢀmeꢀ
thylꢀ1,2ꢀphenylenediamines (4d), respectively, with 4ꢀhydroxyꢀ
thiazolidine 1a (refluxing for 8 and 3 h). Analytically pure
samples were prepared by recrystallization.
4,5ꢀDihydroꢀ3ꢀphenylꢀ1ꢀ(4ꢀtolylimino)thiazolo[3,4ꢀa]quinꢀ
oxalinꢀ4ꢀone (5f), 4,5ꢀdihydroꢀ1ꢀ(2ꢀnaphthylimino)ꢀ3ꢀphenylꢀ
thiazolo[3,4ꢀa]quinoxalinꢀ4ꢀone (5g), 4,5ꢀdihydroꢀ3ꢀphenylꢀ1ꢀ
(thiazolꢀ2´ꢀylimino)thiazolo[3,4ꢀa]quinoxalinꢀ4ꢀone (5h), and
4,5ꢀdihydroꢀ7,8ꢀdifluoroꢀ3ꢀphenylꢀ1ꢀ(thiazolꢀ2´ꢀylimino)thiazoꢀ
lo[3,4ꢀa]quinoxalinꢀ4ꢀone (5i) were synthesized analogously usꢀ
ing the corresponding tautomeric mixtures, which were preꢀ
pared from nonsymmetrical NꢀphenylꢀN´ꢀsubstituted thioureas,
and isolated by recrystallization from DMSO of a crystalline
substance obtained after repeated washing of the residue with a
hot 1 : 1 MeOH—PriOH mixture. The combined filtrates were
concentrated and analytically pure thiazoloquinoxaline 5a was
obtained.
Xꢀray diffraction study of compound 5b was performed on an
automated fourꢀcircle EnrafꢀNonius CADꢀ4 diffractometer.
Crystals of 5b, C24H19F2N3O2S2, are monoclinic. At 20 °C
* These data can be obtained, free of charge, on application to
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax: +44(0)
1223ꢀ336033, eꢀmail: deposit@ccdc.cam.ac.uk).

2576
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 11, November, 2004
Mamedov et al.
15. S. K. Kotovskaya, N. M. Perova, Z. M. Baskakova, S. A.
Romanova, V. N. Charushin, and O. N. Chupakhin, Zh. Org.
Khim., 2001, 27, 598 [Russ. J. Org. Chem., 2001, 27 (Engl.
Transl.)].
16. V. A. Mamedov, A. A. Kalinin, A. T. Gubaidullin, I. A.
Litvinov, N. M. Azancheev, and Ya. A. Levin, Zh. Org.
Khim., 2004, 39, 123 [Russ. J. Org. Chem., 2004, 39 (Engl.
Transl.)].
This study was financially supported by the Russian
Foundation for Basic Research (Project Nos. 03ꢀ03ꢀ
32865, 02ꢀ03ꢀ32280, and 04ꢀ03ꢀ96090), the Foundation
of the President of the Russian Federation (Program
"Leading Scientific Schools," Grant 1766.2003.3), and
the Charity Foundation for Support of Russian Science.
17. K. V. Vatsuro and G. L. Mishchenko, Imennye reaktsii v
organicheskoi khimii [Name Reactions in Organic Chemistry],
Khimiya, Moscow, 1976, 67 (in Russian).
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Received March 15, 2004;
in revised form June 8, 2004