Fused polycyclic nitrogen-containing heterocycles : 1117. 4-Hydroxy-3-phenyl-2-(2-pyridylimino)-and 4-hydroxy-2-phenyl-3-(2-pyridyl) thiazolidines and related thiazolo[3,4-a]quinoxalines

Article abstract of DOI:10.1007/s11172-007-0365-9

The condensation of methyl phenylchloropyruvate with 1-phenyl-3-(2-pyridyl) thiourea and its 3-and 4-picolyl homologs affords the corresponding 4-hydroxythiazolidines, which react with o-phenylenediamine to give one of two possible thiazolo[3,4-a]quinoxalines containing the pyridyl-or picolylimine substituents at position 1. 3a-Hydroxy-3-phenylimino-1-(2-pyridyl)thiazolo[3,4- a]quinoxalin-4-(3H,5H)-one, which is a covalent hydrate of the final product, was isolated as an intermediate in this reaction.

Full text of DOI:10.1007/s11172-007-0365-9

Russian Chemical Bulletin, International Edition, Vol. 56, No. 11, pp. 2308—2314, November, 2007
2308
Fused polycyclic nitrogenꢀcontaining heterocycles
17.* 4ꢀHydroxyꢀ3ꢀphenylꢀ2ꢀ(2ꢀpyridylimino)ꢀ and
4ꢀhydroxyꢀ2ꢀphenylꢀ3ꢀ(2ꢀpyridyl)thiazolidines and related thiazolo[3,4ꢀa]quinoxalines**
V. A. Mamedov,ꢀ N. A. Zhukova, T. N. Beschastnova, Ya. A. Levin, A. T. Gubaidullin, 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 methyl phenylchloropyruvate with 1ꢀphenylꢀ3ꢀ(2ꢀpyridyl)thiourea
and its 3ꢀ and 4ꢀpicolyl homologs affords the corresponding 4ꢀhydroxythiazolidines, which
react with oꢀphenylenediamine to give one of two possible thiazolo[3,4ꢀa]quinoxalines conꢀ
taining the pyridylꢀ or picolylimine substituents at position 1. 3aꢀHydroxyꢀ3ꢀphenyliminoꢀ1ꢀ
(2ꢀpyridyl)thiazolo[3,4ꢀa]quinoxalinꢀ4ꢀ(3H,5H )ꢀone, which is a covalent hydrate of the final
product, was isolated as an intermediate in this reaction.
Key words: Hantzsch reaction, 4ꢀhydroxythiazolidines, thiazolo[3,4ꢀa]quinoxalines, covaꢀ
lent hydrate, IR spectra, NMR spectra, Xꢀray diffraction study.
Scheme 1
Azolo[a]quinoxalines and their 4,5ꢀdihydro derivaꢀ
tives exhibit various biological and pharmacological acꢀ
tivities2—7 and are used in the synthesis of many biologiꢀ
cally important compounds and drugs.8—11 However, unꢀ
like the imidazo[1,5ꢀa]quinoxaline system, whose synꢀ
thesis and properties were studied in sufficient detail, the
methods for the synthesis of thiazolo[3,4ꢀa]quinoxalines,
whose first representatives were prepared as late
as 1982,12,13 have received little attention.
Earlier, we have developed a procedure for the synꢀ
thesis of thiazolo[3,4ꢀa]quinoxalines involving the casꢀ
cade annulation of the thiazolopyrazine system with the
benzene moiety by the reaction of the intermediate
Hantzsch reaction products, viz., 4ꢀhydroxyꢀ4ꢀmethoxyꢀ
carbonylꢀ3,5ꢀdiphenylꢀ2ꢀphenyliminothiazolidine 1a (see
Refs 14—19) and its pꢀtolyl, 2ꢀnaphthyl, and thiazolꢀ2ꢀyl
analogs,17 with 1,2ꢀphenylenediamines in boiling acetic
acid (Scheme 1).
R = H, Me, NO2
This method is based on the fact that 4ꢀhydroxyꢀ
thiazolidine 1a exists in solution as an equilibrium mixꢀ
ture15,19 of two diastereoisomeric forms and their openꢀ
chain 1,2ꢀdicarbonyl tautomer, which can react with
1,2ꢀphenylenediamines. It should be noted that ketone
carbonyl is present in the protected form (as the geminal
hydroxyamino group) in cyclic tautomer 1a as well.
Hence, the latter compound can be considered as the
synthetic equivalent of the 1,2ꢀdicarbonyl synthon.
However, the synthetic potential of 4ꢀhydroxyꢀ
thiazolidines 1 is, on the whole, poorly known.20,21 In the
present study, we examined the possibility of application
of this method in the synthesis of thiazolo[3,4ꢀa]quinꢀ
oxalines containing the pyridyl or 3ꢀ and 4ꢀpicolyl groups,
whose presence will allow, if required, the preparation of
waterꢀsoluble salts of this fused polycyclic heterocycle.
The condensation of chloropyruvate 3 with 3ꢀphenylꢀ
1ꢀ(2ꢀpyridyl)thiourea and its picolyl homologs 4b—d afꢀ
forded products, which correspond in elemental compoꢀ
sition to the expected isomeric 4ꢀhydroxythiazolidines.
Unlike 4ꢀhydroxythiazolidine, which we have synthesized
* For Part 16, see Ref. 1.
** Dedicated to Academician G. A. Abakumov on the occasion
of his 70th birthday.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2230—2236, November, 2007.
1066ꢀ5285/07/5611ꢀ2308 © 2007 Springer Science+Business Media, Inc.

Fused polycyclic nitrogenꢀcontaining heterocycles
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 11, November, 2007 2309
earlier from symmetrical N,N´ꢀdiphenylthiourea,14—19
thiazolidines can be derived as two regioisomeric forms
1b—d and 1´b—d from its unsymmetrical pyridyl analogs
(Scheme 2).
Table 1. Changes with time in the ratio of the isomers* of
4ꢀhydroxythiazolidines in DMSOꢀd6 at room temperature
Sample
Isoꢀ
mer
δ **
Irel (%)
H
OMe SCH(Ph)
0
0.5 h 24 h
Scheme 2
1b + 1´b + 5b
1
2
3
4
5
6
1
2
1
2
3
4
3.17
3.18
3.19
3.58
3.60
3.61
3.15
3.56
3.14
3.17
3.58
3.59
5.02
5.05
5.00
5.38
5.20
5.46
4.97
5.30
4.99
4.97
5.31
5.18
0
0
0
100
0
0
0
100
0
0
100
0
2
0
3
84
4
7
5
95
7
6
74
13
5
4
22
54
8
7
1c + 1´c + 5c
1d + 1´d + 5d
27
73
5
22
64
9
* Calculated by averaging the relative integrated intensities of
the methoxy and methine protons.
** The chemical shifts remain unchanged during the measureꢀ
ments.
Ar = Ph (a),
(b),
(c),
(d)
Scheme 3
According to the 1H NMR and IR spectra of the reacꢀ
tion products, the ratio of the components in these mixꢀ
tures strongly depends on the conditions, under which
the spectra are measured, and on the nature of the subꢀ
stituent Ar, as well as on the conditions of isolation and
purification of the products. The detailed discussion of
the regioꢀ and diastereomeric compositions of these prodꢀ
ucts is beyond the scope of the present study. However, it
should be noted that new peaks appeared in the 1H NMR
spectra during the storage of the solutions (Table 1), which
is indicative of a gradual complication of the tautomeric
composition of these products. In particular, the number
of initial singlets for the methoxy and methine protons in
the spectra of product 1c+1´c is doubled with time. For
two other products under study, the appearance of mulꢀ
tiplets is observed. For solutions of all three products, the
sum of the integrated intensities of the peaks for these
groups remains equal to 1 : 3 at least, for 1 day, the chemiꢀ
cal shifts being also unchanged.
The nature of the tautomerism responsible for the comꢀ
plication of the 1H NMR spectra is, apparently, the same
as that of the aboveꢀmentioned tautomerism of comꢀ
pound 1a15 (Scheme 3).
The spectra can be additionally complicated due to
the fact that cyclic tautomers 1b—d and 1´b—d exist as
two diastereomers, and openꢀchain tautomer 5 consists of
two "subtautomers" resulting from the amidine tautomerꢀ
ism (in the major tautomer, the C=N bond is conjugated
with the pyridyl substituent, which is more electronꢀwithꢀ
drawing than the phenyl substituent).22,23
The IR spectra of crystalline samples of the reaction
products have many features in common with the IR specꢀ
trum of a crystalline sample of cyclic thiazolidine 1a,
which has been comprehensively studied.15 These spectra
do not contain absorption bands at 3400 cm–1 characterꢀ
istic of νN—H vibrations, which should be present in the
IR spectra of the openꢀchain isothioureide structures.15
At the same time, these spectra show broad absorpꢀ
tion bands at 3452 cm–1 (1b), 3440 cm–1 (1c), and
3448 cm–1 (1d), which can be assigned to νO—H vibraꢀ
tions of the hydroxy groups of 4ꢀhydroxythiazolidines 1
and/or 1´. Therefore, like the reaction of chloropyruvate
3 with N,N´ꢀdiphenylthiourea described earlier,15 the reꢀ
actions with NꢀphenylꢀNꢀpyridylthioureas 4b—d also proꢀ
duce compounds having the cyclic structure (4ꢀhydroxyꢀ
thiazolidines) in the crystalline phase as the final products.
The condensation of pyridylꢀcontaining thiazolidines
1b—d + 1´b—d with oꢀphenylenediamine, like that of
diphenylthiazolidine 1a, affords the expected thiazoꢀ
lo[3,4ꢀa]quinoxalinones 2b—d. However, unlike thiazolꢀ
idines prepared from other unsymmetrical N,N´ꢀdisubꢀ
stituted thioureas, which give mixtures of isomeric
thiazolo[3,4ꢀa]quinoxalines in the reactions with oꢀpheꢀ
nylenediamine,18,19 the compounds under study give exꢀ

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Russ.Chem.Bull., Int.Ed., Vol. 56, No. 11, November, 2007
Mamedov et al.
clusively quinoxalines 2b—d (rather than mixtures) conꢀ
taining the pyridylimine groups at position 1, i.e., the
condensation is accompanied by elimination of aniline
but not of 2ꢀaminopyridine or 2ꢀaminopicolins. Thereꢀ
fore, we solved the problem of the synthesis of thiazoꢀ
lo[3,4ꢀa]quinoxalines containing the pyridyl or picolyl
groups (Scheme 4).
C(16)
C(15)
C(14)
C(17)
C(12)
N(13)
S(2)
N(11)
C(8)
C(9A)
C(1)
C(9)
N(10)
C(7)
C(6)
Scheme 4
C(3)
N(5)
C(4)
C(5A)
C(4A)
C(30)
O(4A)
C(31)
C(32)
C(33)
O(4)
C(35)
C(34)
Fig. 1. Molecular geometry of compound 6b in the crystal strucꢀ
ture. The DMSO solvent molecule is omitted.
disordered over two positions with occupancies of 0.53
and 0.47. The molecule of compound 6b is chiral, and
compound 6b crystallizes in the noncentrosymmetric
space group P212121. However, the refinement of the exꢀ
perimental data showed that the structure is a racemic
twin with a ratio of 0.55 : 0.45. This did not allow us to
determine the absolute configurations at the chiral carbon
atoms. The relative configurations at the C(3) and C(4a)
atoms are S and R, respectively. The phenylimine group
has a Z configuration.
The presence of sp3ꢀhybridized carbon atoms in the
tricyclic moiety of compound 6b is responsible for the
nonplanarity of this fragment and hinders the formation
of π—π interactions characteristic of the crystal packing
of the thiazolo[3,4ꢀa]quinoxaline systems.17,19 At the same
time, the presence of the DMSO solvent molecule in the
crystal hinders the formation of hydrogenꢀbonded dimers
through N—H...O pairwise interactions characteristic of
such compounds. This phenomenon has been discussed
in detail in our earlier study.24 In the case under considerꢀ
ation, hydrogenꢀbonded chains are formed along the
crystallographic 0a axis via O—H...O hydrogen bonds;
N—H...O interactions are observed between the carbaꢀ
moyl group and the oxygen atom of the DMSO molecule.
Upon further heating in acetic acid, covalent hydrate
6b loses the water molecule and is transformed into
thiazolo[3,4ꢀa]quinoxaline 2b in virtually quantitative
yield.
Ar = Ph (a),
(b),
(c),
(d)
Unlike the reaction of thiazolidine 1a with orthoꢀpheꢀ
nylenediamine yielding the final product in 3—5 min, the
reactions of pyridylꢀcontaining thiazolidines 1b—d with
orthoꢀphenylenediamine are completed in ~1 h under
analogous conditions. Slower rates of the reactions under
consideration allow the isolation of intermediate prodꢀ
ucts. The formation of a crystalline precipitate different
from the final product is observed 5 min after the beginꢀ
ning of refluxing. Using the reaction of thiazolidine 1b as
an example, we demonstrated that this compound is a
covalent hydrate (compound 6b) of the final thiazoꢀ
lo[3,4ꢀa]quinoxaline 2b. The structure of compound 6b
was established by spectroscopic methods and Xꢀray difꢀ
fraction.
The isolation of intermediate covalent hydrate 6b of
the final product, thiazolo[3,4ꢀa]quinoxaline 2b, allows
the refinement of the mechanisms of formation of thiazoꢀ
lo[3,4ꢀa]quinoxalines 2 in the reactions under considerꢀ
Molecule 6b occupies a general position in the tetꢀ
ragonal unit cell (Fig. 1). The crystal structure includes
a DMSO molecule. In the crystal, the solvent molecule is

Fused polycyclic nitrogenꢀcontaining heterocycles
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 11, November, 2007 2311
ation (Scheme 5). These mechanisms have been discussed
in our earlier studies.17,19
tautomer D destabilized by the loss of aromaticity,27 this
process being unlikely. The elimination of aniline giving
rise to the compound E, which is the protonated form of
compound 6, is a more probable process (Scheme 6).
Scheme 5
Scheme 6
Apparently, the product A, which is generated in the
first step as a result of the reaction of openꢀchain ketone 5
and/or its protected cyclic forms 1 or 1´ with orthoꢀpheꢀ
nylenediamine, undergoes intramolecular amidation folꢀ
lowed by the addition of the amino group of the aminal
system at the amidine carbon atom to give the thiazoꢀ
lo[3,4ꢀa]quinoxaline system B containing the geminal
phenylamino and pyridylamino substituents at position 1.
The subsequent acidꢀcatalyzed elimination of aniline (isoꢀ
lated as acetanilide) from the intermediate B affords coꢀ
valent hydrates 6b—d, whose dehydration under the reacꢀ
tion conditions gives the final products 2b—d.
The explanation of the formation of only one of two
possible isomers of thiazolo[3,4ꢀa]quinoxalines containꢀ
ing exclusively the pyridylimine group at position 1 preꢀ
sents another problem. Evidently, this is due to the comꢀ
petitive elimination of the geminal arylamino substituents
in the intermediate B. Since the reaction is performed in
an acidic medium, the higher basicity of the pyridylamino
group compared to the phenylamino group (pKa of
2ꢀaminopyridine and aniline are 7.2 (see Ref. 25) and 4.6
(see Ref. 26), respectively) should lead to the predomiꢀ
nant protonation of the aminopyridine moiety and elimiꢀ
nation of aminopyridine giving rise to compound 7. Howꢀ
ever, this is not the case. The reaction is accompanied by
elimination of the phenylamino fragment and gives comꢀ
pound 2. There are at least two, apparently parallel, facꢀ
tors responsible for this result. These factors are associꢀ
ated with the intramolecular proton or acetyl transfer from
the pyridine to phenylamino nitrogen atom.
Another factor is that the preliminary acetylation of
the intermediate B at the pyridine nitrogen atom with
acetic acid affords the intermediate F, in which the intraꢀ
molecular transfer of the acetyl group to the phenylamino
nitrogen atom occurs (the intramolecular catalysis of
acetylation of amines with pyridine facilitated by the spaꢀ
tial proximity of the pyridine and aniline nitrogen atoms).
This gives rise to the intermediate G, from which acetꢀ
anilide is easily eliminated to form the aboveꢀconsidered
intermediate E (Scheme 7).
Scheme 7
One factor is that aminopyridine can be eliminated
from the intermediate C (the form of the structure B
protonated at the pyridine nitrogen atom) only as the

2312
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 11, November, 2007
Mamedov et al.
M.p. 137—139 °C (PriOH). Found (%): C, 64.72; H, 4.26;
N, 9.90; S, 8.38. C22H19N3O3S. Calculated (%): C, 65.17;
H, 4.72; N, 10.36; S, 7.91. IR, ν/cm–1: 3452 (OH); 3059—2853,
1738 (C=O); 1629 (C=N). 1H NMR, δ: 3.17, 3.18, 3.19,
3.58, 3.60, and 3.61 (all s, 3 H, OMe); 5.00, 5.02, 5.06, 5.20,
5.33, and 5.46 (all s, 1 H, CH); 6.63—8.51 (m, 15 H, 2 Ph,
H(2)—H(5) pyridine, OH).
4ꢀHydroxyꢀ4ꢀmethoxycarbonylꢀ2ꢀ(3ꢀmethylꢀ2ꢀpyridylimino)ꢀ
3,5ꢀdiphenylthiazolidine (1c) and 4ꢀhydroxyꢀ4ꢀmethoxycarbonylꢀ
3ꢀ(3ꢀmethylꢀ2ꢀpyridyl)ꢀ5ꢀphenylꢀ2ꢀphenyliminothiazolidine (1´c).
Compound 1´c was synthesized as described above starting from
Nꢀ(3ꢀmethylꢀ2ꢀpyridyl)ꢀN´ꢀphenylthiourea 4c. The yield was
46%, m.p. 130—134 °C (PriOH). Found (%): C, 65.55; H, 4.91;
N, 9.76; S, 7.38. C23H21N3O3S. Calculated (%): C, 65.85;
H, 5.05; N, 10.02; 11.44; S, 7.64. IR, ν/cm–1: 3440 (OH);
3055—2853 (NH); 1757 (C=O); 1731 (C=O); 1623 (C=N).
1H NMR, δ: 2.00 (s, 6 H, 2 Me); 3.15 and 3.56 (both s, 3 H,
OMe); 4.97 and 5.30 (both s, 1 H, CH); 6.90—8.15 (m, 14 H,
2 Ph, H(2)—H(4) pyridine, OH).
4ꢀHydroxyꢀ4ꢀmethoxycarbonylꢀ2ꢀ(4ꢀmethylꢀ2ꢀpyridylimino)ꢀ
3,5ꢀdiphenylthiazolidine (1d) and 4ꢀhydroxyꢀ4ꢀmethoxycarbonylꢀ
3ꢀ(4ꢀmethylꢀ2ꢀpyridyl)ꢀ5ꢀphenylꢀ2ꢀphenyliminothiazolidine (1´d).
Compound 1´d was synthesized as described above starting
from Nꢀ(4ꢀmethylꢀ2ꢀpyridyl)ꢀN´ꢀphenylthiourea 4d. The yield
was 67%, m.p. 143—145 °C (PriOH). Found (%): C, 65.50;
H, 4.88; N, 9.87; S, 7.29. C23H21N3O3S. Calculated (%):
C, 65.85; H, 5.05; N, 10.02; 11.44; S, 7.64. IR, ν/cm–1: 3448
(OH); 3214—2951 (NH); 1748 (C=O); 1613 (C=N). 1H NMR,
δ: 2.21, 2.22, 2.31, and 2.34 (all s, 3 H, Me); 3.14, 3.17, 3.57,
and 3.58 (all s, 3 H, OMe); 4.97, 4.99, 5.18, and 5.31 (all s,
1 H each, CH); 6.63—8.18 (m, 14 H, 2 Ph, H(2), H(3), H(5) pyꢀ
ridine, OH).
3ꢀPhenylꢀ1ꢀ(2ꢀpyridylimino)thiazolo[3,4ꢀa]quinoxalinꢀ4ꢀ
(5H )ꢀone (2b). A solution of oꢀphenylenediamine (0.53 g,
4.90 mmol) and 4ꢀhydroxythiazolidine (1b+1´b) (2 g,
4.90 mmol) in AcOH (50 mL) was refluxed for 1 h. The paleꢀ
yellow crystals that precipitated were filtered off. Analytically
pure compound 2b was obtained in a yield of 1.39 g (77%).
M.p. > 300 °C. Found (%): C, 67.79; H, 3.66; N, 15.01; S, 8.35.
Experimental
The 1H NMR spectra were recorded on
a Bruker
AVANCEꢀ600 spectrometer (600.00 MHz) in DMSOꢀd6. The
chemical shifts are given on the δ scale. The IR spectra were
measured on a Bruker Vectorꢀ22 Fourierꢀtransform spectroꢀ
meter in KBr pellets. The melting points were determined on a
Boetius hotꢀstage apparatus. Methyl phenylchloropyruvate 3 (see
Ref. 28), 1ꢀ(2ꢀpyridyl)ꢀ3ꢀphenylthiourea, and its picolyl hoꢀ
mologs 4b—d (see Ref. 29) were synthesized according to known
procedures.
N´ꢀPhenylꢀNꢀ(2ꢀpyridyl)thiourea (4b). Phenyl isothiocyanate
(6 g, 0.0444 mol) was added to a solution of 2ꢀaminopyridine
(4 g, 0.0426 mol) in toluene (50 mL). The reaction mixture was
refluxed for 5 h. The white crystals that precipitated were filꢀ
tered off. The yield was 8.3 g (97%), m.p. 172 °C (cf. lit. data29
:
171—172 °C). IR, ν/cm–1: 3219—2853 (NH); 1598, 1555, 1532,
1495, 1437, 1428. 1H NMR, δ: 7.11 (dd, 1 H, H(5), J = 6.70 Hz,
J = 5.20 Hz); 7.21 (dd, 1 H, pꢀHPh, J = 7.84 Hz, J = 7.45 Hz);
7.23 (d, 1 H, H(3), J = 8.50 Hz); 7.39 (dd, 2 H, 2 mꢀHPh, J =
7.84 Hz, J = 7.45 Hz); 7.70 (dd, 2 H, 2 oꢀHPh, J = 7.84 Hz); 7.84
(ddd, 1 H, H(4), J = 8.50 Hz, J = 6.70 Hz, J = 1.40 Hz); 8.31 (d,
1 H, H(6), J = 5.20 Hz); 10.87 (s, 2 H, 2 NH).
Nꢀ(3ꢀMethylꢀ2ꢀpyridyl)ꢀN´ꢀphenylthiourea (4c). Compound
4c was synthesized as described above starting from 2ꢀaminoꢀ3ꢀ
methylpyridine. The yield was 67%, m.p. 130—135 °C (from
EtOH) (cf. lit. data30: 123—124 °C). Found (%): C, 64.17;
H, 5.39; N, 17.27; S, 13.18. C13H13N3S. Calculated (%):
C, 64.18; H, 5.33; N, 17.32; S, 13.15. IR, ν/cm–1: 3399—2854
(NH); 1631, 1595, 1573, 1516, 1500, 1468, 1453, 1417. 1H NMR,
δ: 2.37 (s, 3 H, Me); 7.11 (dd, 1 H, H(5), J = 7.20 Hz, J =
4.60 Hz); 7.22 (dd, 1 H, pꢀHPh, J = 7.34 Hz, J = 7.33 Hz); 7.39
(dd, 2 H, 2 mꢀHPh, J = 7.58 Hz, J = 8.07 Hz); 7.68 (d, 2 H,
2 oꢀHPh, J = 7.58); 7.73 (d, 1 H, H(4), J = 7.20 Hz); 8.23 (d,
1 H, H(6), J = 4.60 Hz), 9.75 (s, 2 H, 2 NH).
N´ꢀ(4ꢀMethylꢀ2ꢀpyridyl)ꢀN´ꢀphenylthiourea (4d). Comꢀ
pound 4d was synthesized as described above starting
from 2ꢀaminoꢀ4ꢀmethylpyridine. The yield was 79%, m.p.
156—157 °C (from EtOH) (cf. lit. data30: 161.5—162.5 °C).
Found (%): C, 64.17; H, 5.39; N, 17.27; S, 13.18. C13H13N3S.
Calculated (%): C, 64.15; H, 5.34; N, 17.30; S, 13.16. IR,
ν/cm–1: 3218—2854 (NH); 1615, 1597, 1562, 1531, 1500, 1483,
C
21H14N4OS. Calculated (%): C, 68.09; H, 3.81; N, 15.12;
S, 8.65. IR, ν/cm–1: 3185—2857 (NH); 1679 (C=O); 1607
(C=N); 1586, 1564, 1532, 1489, 1462, 1430, 1404. 1H NMR, δ:
7.08 (ddd, 1 H, H(5) pyridine, J = 7.10 Hz, J = 4.80 Hz, J =
0.78 Hz); 7.19 (dd, 1 H, H(6), J = 7.50 Hz, J = 1.60 Hz); 7.22
(ddd, 1 H, H(8), J = 8.40 Hz, J = 7.50 Hz, J = 1.60 Hz); 7.27
(ddd, 1 H, H(7), J = 7.60 Hz, J = 7.60 Hz, J = 1.30 Hz); 7.34 (d,
1 H, H(3) pyridine, J = 8.10 Hz); 7.41—7.43 (m, 3 H, phenyl);
7.55—7.57 (m, 2 H, phenyl); 7.82 (ddd, 1 H, H(4) pyridine, J =
8.10 Hz, J = 7.60 Hz, J = 1.96 Hz); 8.49 (dd, 1 H, H(6)
pyridine, J = 4.96 Hz, J = 1.00 Hz); 10.00 (d, 1 H, (H9), J =
8.40 Hz); 11.27 (s, 1 H, NH). The filtrate was treated with a 5%
NaHCO3 solution. The precipitate that formed was filtered off,
washed with water, dried in air, and recrystallized from DMSO.
Compound 2b was additionally obtained in a yield of 0.08 g (4%).
The aqueous layer was extracted with ethyl acetate (3×20 mL).
Ethyl acetate was evaporated, the residue was treated with diꢀ
ethyl ether, and the orange precipitate was filtered off. Acetꢀ
anilide was obtained in a yield of 0.10 g, m.p. 110—113 °C. IR,
ν/cm–1: 3292—2853 (NH); 1664 (C=O); 1619, 1599, 1556.
1
1447, 1404. H NMR, δ: 2.31 (s, 3 H, Me); 6.95 (d, 1 H, H(5),
J = 5.00 Hz); 7.08 (s, 1 H, H(3); 7.21 (dd, 1 H, pꢀHPh, J =
7.58 Hz, J = 7.34 Hz); 7.39 (dd, 2 H, 2 mꢀHPh, J = 7.58 Hz, J =
8.07 Hz); 7.69 (d, 2 H, 2 oꢀHPh, J = 7.58 Hz); 8.18 (d, 1 H,
H(6), J = 5.00 Hz); 10.77 (s, 2 H, 2 NH).
4ꢀHydroxyꢀ4ꢀmethoxycarbonylꢀ3,5ꢀdiphenylꢀ2ꢀ(2ꢀpyridylꢀ
imino)thiazolidine (1b) and 4ꢀhydroxyꢀ4ꢀmethoxycarbonylꢀ5ꢀpheꢀ
nylꢀ2ꢀphenyliminoꢀ3ꢀ(2ꢀpyridyl)thiazolidine (1´b). Sodium acꢀ
etate (3.6 g, 0.0438 mol) was added to a solution of N´ꢀphenylꢀ
N´ꢀ(2ꢀpyridyl)thiourea 4b (4 g, 0.0175 mol) in CH2Cl2 (150 mL).
The reaction mixture was cooled to a temperature from
–15 to –20 °C, and a solution of methyl phenylchloropyruvate
(3.7 g, 0.0175 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 the aqueous
layer was extracted with CHCl3 (2×20 mL). The organic layer
and the extract were combined and dried with MgSO4, the solꢀ
vent was evaporated, and the residue was treated with PriOH.
A mixture of (1b+1´b) was obtained in a yield of 3.4 g (50%).
1H NMR, δ: 2.03 (s, 3 H, COMe); 7.21 (dd, 1 H, pꢀHPh
J = 7.80 Hz, J = 7.32 Hz); 7.27 (dd, 2 H, 2 mꢀHPh, J = 7.80 Hz,
,

Fused polycyclic nitrogenꢀcontaining heterocycles
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 11, November, 2007 2313
J = 7.32 Hz); 7.56 (d, 2 H, 2 oꢀHPh, J = 7.80 Hz); 9.88
(s, 1 H, NH).
and then anisotropically using the SHELXLꢀ9733 and WinGX34
program packages. The coordinates of the hydrogen atoms of
the hydroxy and amino groups were located in difference elecꢀ
tron density maps and refined isotropically. The coordinates of
other hydrogen atoms were calculated based on the stereochemiꢀ
cal criteria and refined using a riding model. The DMSO molꢀ
ecule is disordered over two positions with occupancies of 0.53
and 0.47. The crystal structure of compound 6b is a racemic
twin with a ratio of 0.55 : 0.45. The final R factors were R = 0.0551
and Rw = 0.1403 based on 2286 reflections with F > 2σ. The
figure was drawn with the use of the PLATON program.35 The
atomic coordinates and displacement parameters for comꢀ
pound 6b were deposited with the Cambridge Structural Dataꢀ
base (CCDC 640124).
1ꢀ(3ꢀMethylꢀ2ꢀpyridyl)iminoꢀ3ꢀphenylthiazolo[3,4ꢀa]quinꢀ
oxalinꢀ4ꢀ(5H )ꢀone (2c). Compound 2c was synthesized as deꢀ
scribed above starting from 4ꢀhydroxythiazolidine 1c. The yield
was 80%, m.p. > 300 °C. Found (%): C, 68.39; H, 4.04; N, 14.45;
S, 8.24. C22H16N4OS. Calculated (%): C, 68.73; H, 4.19;
N, 14.57; S, 8.34. IR, ν/cm–1: 3185—2853 (NH); 1681 (C=O);
1606 (C=N); 1573, 1532, 1488, 1463, 1447, 1436, 1418.
1H NMR, δ: 2.48 (s, 3 H, Me); 7.01 (dd, 1 H, H(5) pyridine, J =
7.20 Hz, J = 4.80 Hz); 7.21 (dd, 1 H, H(6), J = 7.60 Hz, J =
1.60 Hz); 7.23 (ddd, 1 H, H(8), J = 8.70 Hz, J = 7.30 Hz, J =
1.80 Hz); 7.28 (ddd, 1 H, H(7), J = 7.60 Hz, J = 7.30 Hz, J =
1.30 Hz); 7.42—7.45 (m, 3 H, phenyl); 7.55—7.57 (m, 2 H,
phenyl); 7.70 (d, 1 H, H(4) pyridine, J = 7.20 Hz); 8.34 (d, 1 H,
H(6) pyridine, J = 4.80 Hz); 10.01 (d, 1 H, H(9), J = 8.60 Hz);
11.28 (s, 1 H, NH).
1ꢀ(4ꢀMethylꢀ2ꢀpyridyl)iminoꢀ3ꢀphenylthiazolo[3,4ꢀa]ꢀquinꢀ
oxalinꢀ4ꢀ(5H )ꢀone (2d). Compound 2d was synthesized as deꢀ
scribed above starting from 4ꢀhydroxythiazolidine 1d. The yield
was 83%, m.p. > 300 °C. Found (%): C, 68.48; H, 4.07; N, 14.37;
S, 8.19. C22H16N4OS. Calculated (%): C, 68.73; H, 4.19;
N, 14.57; S, 8.34. IR, ν/cm–1: 3185—2764 (NH); 1682 (C=O);
1623 (C=N); 1605, 1589, 1559, 1521, 1496. 1H NMR, δ: 2.37 (s,
3 H, Me); 6.92 (d, H(5) pyridine, J = 4.70 Hz); 7.18 (s, 1 H,
H(3) pyridine); 7.19 (dd, 1 H, H(6), J = 7.30 Hz, J = 1.60 Hz);
7.21 (ddd, 1 H, H(8), J = 8.40 Hz, J = 7.30 Hz, J = 1.60 Hz);
7.27 (ddd, 1 H, H(7), J = 7.30 Hz, J = 7.30 Hz, J = 1.60 Hz);
7.41—7.45 (m, 3 H, phenyl); 7.54—7.56 (m, 2 H, phenyl); 8.33
(d, 1 H, H(6) pyridine, J = 5.20 Hz); 9.99 (d, 1 H, H(9), J =
8.40 Hz); 11.24 (s, 1 H, NH).
This study was financially supported by the Russian
Foundation for Basic Research (Project Nos 07ꢀ03ꢀ
00613ꢀa and 05ꢀ03ꢀ33008ꢀa).
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Received June 14, 2007;
in revised form October 23, 2007