Fused polycyclic nitrogen-containing heterocycles 15.* 1,3-bis(4-hydroxy-4-methoxycarbonyl-3,5-diphenylthiazolidin-2-ylideneamino) -benzene in the synthesis of thiazolo[3,4-a]quinoxalines

Article abstract of DOI:10.1007/s11172-006-0472-z

Reactions of methyl chloro(phenyl)pyruvate with 1,3-bis(phenylthioureido) benzene easily afforded 1,3-bis(4-hydroxy-4-methoxycarbonyl-3,5- diphenylthiazolidin-2-ylideneamino)benzene. Reactions of the latter with 1,2-phenylenediamines gave various derivati

Full text of DOI:10.1007/s11172-006-0472-z

Russian Chemical Bulletin, International Edition, Vol. 55, No. 9, pp. 1670—1676, September, 2006
1670
Fused polycyclic nitrogenꢀcontaining heterocycles
15.* 1,3ꢀBis(4ꢀhydroxyꢀ4ꢀmethoxycarbonylꢀ3,5ꢀdiphenylthiazolidinꢀ2ꢀylideneamino)ꢀ
benzene in the synthesis of thiazolo[3,4ꢀa]quinoxalines
a
b
a
V. A. Mamedov,a E. A. Khafizova, E. A. Berdnikov, Ya. A. Levin,
ꢀ
I. Kh. Rizvanov,a I. Bauer,c and W. D. Habicherc
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) 273 2253. Eꢀmail: mamedov@iopc.knc.ru
bKazan State University,
18 ul. Kremlevskaya, 420008 Kazan, Russian Federation
cInstitute of Organic Chemistry, Dresden University of Technology,
13 Mommsenstrasse, Dꢀ01062 Dresden, Germany
Reactions of methyl chloro(phenyl)pyruvate with 1,3ꢀbis(phenylthioureido)benzene easily
afforded 1,3ꢀbis(4ꢀhydroxyꢀ4ꢀmethoxycarbonylꢀ3,5ꢀdiphenylthiazolidinꢀ2ꢀylideneamino)benꢀ
zene. Reactions of the latter with 1,2ꢀphenylenediamines gave various derivatives of thiazoꢀ
lo[3,4ꢀa]quinoxalines, including their bisanalogs.
Key words: thiazolidines, thiazolo[3,4ꢀa]quinoxalines, tautomerism, Hantzsch reaction,
1,2ꢀphenylenediamines.
Azolo[a]quinoxalines and their 4,5ꢀdihydro derivaꢀ
tives exhibit various biological and pharmacological propꢀ
erties2—7 and are used in the synthesis of many biologiꢀ
cally important compounds and drugs.8—11 However, in
contrast to the wellꢀstudied synthesis and properties of
the imidazo[1,5ꢀa]quinoxaline system, methods for the
synthesis of thiazolo[3,4ꢀa]quinoxalines 1 first obtained12
as late as 1982 remain poorly investigated. Known routes
to compounds of this type12—21 are based on three differꢀ
ent approaches.
The first approach involves replacement of the haloꢀ
gen atom in 3ꢀ(αꢀhaloalkyl)quinoxalinꢀ2ꢀones 2 (X = Cl,
R = H, and Y = Ph or 2,4ꢀCl2C6H3 and X = Br, Y = Me,
and R = H or Et) by thiocyanate, thiourea, or xanthate
residues. The resulting quinoxalines 2 (X = SCN, R = H,
and Y = Ph or 2,4ꢀCl2C6H3)15,16 and 3 (X = NH2,
Y = NH, and Ar = Ph (see Ref. 17) and X = OMe, Y = S,
and Ar = Ph or 2,4ꢀCl2C6H3 (see Ref. 18)) easily undergo
acidꢀcatalyzed cyclization into thiazolo[3,4ꢀa]quinoxaꢀ
* For Part 14, see Ref. 1.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1611—1617, September, 2006.
1066ꢀ5285/06/5509ꢀ1670 © 2006 Springer Science+Business Media, Inc.

Synthesis of thiazolo[3,4ꢀa]quinoxalines
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 9, September, 2006
1671
lines 1 15—18 (except for X = Me, Y = NAc, and R = H
or Et). Thioureido derivatives 4, which predominantly
exist as tautomeric spirothiazolinoquinoxalines, isomerꢀ
ize in acidic media to give thiazolo[3,4ꢀa]quinoxalines 1
(X = Me, Y = NAc, and R = H or Et) in high yields.19
The second approach to the design of the thiazoꢀ
lo[3,4ꢀa]quinoxaline system employs thiazole derivatives
as starting materials, involving intramolecular reducꢀ
tive cyclization of 4ꢀcarboxyꢀ or 4ꢀmethoxycarbonylꢀ3ꢀ
(2ꢀnitrophenyl)thiazolines 5 (R = H, 4ꢀNO2, or 6ꢀNO2;
R´ = H or Me)12,13 and amineꢀcatalyzed intermolecular
cyclization of 4ꢀchloromethylꢀ3ꢀ(2,3,4ꢀtrifluoropheꢀ
nyl)thiazolidineꢀ2ꢀthione 6.20,21
Unlike the first two approaches, according to which a
thiazole molecule is annulated with the already existing
quinoxaline system or vice versa, the third approach inꢀ
volves cascade annulation of the iminothiazolopyrazine
system to benzene in reactions of 4ꢀhydroxyꢀ4ꢀmethoxyꢀ
carbonylꢀ3,5ꢀdiphenylꢀ2ꢀphenyliminothiazolidine15,22—25
(7) with 1,2ꢀphenylenediamines in boiling acetic acid
(Scheme 1). The condensation affords, through eliminaꢀ
tion of methanol, water, and aniline, thiazolo[3,4ꢀa]quinꢀ
oxalines 1 in high yields.
line,32 1,2,4ꢀtriazolo[3,2ꢀa]isoindole,33 10,10´ꢀaryleneꢀ
bis(7Hꢀbenzo[de]ꢀ1,2,4ꢀtriazolo[5,1ꢀa]isoquinolinꢀ7ꢀ
one),33 benzoxazole,34 indole,35 and benzimidazole.36
For this purpose, we used 1,3ꢀbis(phenylthioꢀ
ureido)benzene37 containing two N,N´ꢀdiphenylthiourea
residues and methyl chloro(phenyl)pyruvate (8) as startꢀ
ing materials.
Like N,N´ꢀdiphenylthiourea,25 its bisanalog,
1,3ꢀbis(phenylthioureido)benzene, reacted with chloro
ketone 8 to give stable bishydroxythiazolidine 9 as an
intermediate in the Hantzsch reaction. The structure of
compound 9 was proven by data from elemental analysis,
IR spectroscopy, and mass spectrometry (Scheme 2) and
confirmed by its easy and smooth dehydration with thionyl
chloride into the final product of the Hantzsch bisreaction,
namely, 1,3ꢀbis[N,N´ꢀ(4ꢀmethoxycarbonylꢀ3,5ꢀdiphenylꢀ
thiazolinꢀ2ꢀylidene)]phenylenediamine (10).
Scheme 2
Scheme 1
R = H, Me, NO2
The present work was aimed at applying the last apꢀ
proach to the synthesis of bisthiazoloquinoxalines with
1,3ꢀbis(thiazoloquinoxalinyl)benzenes as examples. These
compounds can not only be biologically active but also be
used as biꢀ and polydentate ligands
or starting reagents in the synthesis
of macrocycles, like other bishetaryl
systems of the type A containing
various heterocyclic fragments such
as those of thiophene,26 pyrazole,27
1,3,4ꢀthiadiazole,28 imidazole,29 thiazole,28,30 1,3,4ꢀoxaꢀ
diazole,31 1,2,4ꢀtriazole,32 1,2,4ꢀtriazolo[3,2ꢀc]quinazoꢀ
1
The H NMR spectrum of product 9 agrees with the
bishydroxythiazolidine structure proposed for it. In conꢀ
trast to its monohydroxythiazolidine prototype 7, the
1H NMR spectrum of bishydroxythiazolidine 9 shows a
set of singlets for the methine and methoxy protons. The
number of the singlets depends on the solvent but the
ratio of the sums of their integral intensities remains conꢀ
stant (1 : 3).
The above complication of the 1H NMR spectrum
can be primarily due to the presence of four chiral centers

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Russ.Chem.Bull., Int.Ed., Vol. 55, No. 9, September, 2006
Mamedov et al.
Scheme 3
in structure 9 (two C(4) and two C(5) atoms), which gives
rise to a great number of diastereomer pairs. Additional
complications may result from Z—E isomerism relative to
two C=N bonds and the partial existence of the hydroxyꢀ
thiazolidine fragments in the openꢀchain isothioureido
form due to ring—chain tautomerism (e.g., structures
9a,d,f). Some of the resulting equilibria are shown in
Scheme 3.
When carrying out the synthesis of bisthiazoloquinoxaꢀ
lines from bishydroxythiazolidine 9 according to the same
scheme as in the synthesis of thiazoloquinoxalines 1 from
monohydroxythiazolidine 7 (see Scheme 1),23,24 the folꢀ
lowing should be kept in mind. In all tautomeric forms,
compound 9 contains several types of electrophilic cenꢀ
ters in both "halves". These are ketone, ester, and hemiꢀ
aminal centers capable of reacting with 1,2ꢀphenylenediꢀ
amine in different sequential orders. The resulting interꢀ
mediates can also undergo, again in different orders, furꢀ
ther transformations leading to both the target product
and other final products. For instance, different sequences
of the transformations of tautomer 9a in a reaction with
1,2ꢀphenylenediamine can yield, through intermediates B,
C, and D, bisthioureidobenzene E, which can close in an
acidic medium an iminothiazoline ring via a nucleophilic
attack of the N(4) atom of the quinoxaline system on
the electrophilic C atom of the isothioureido group
(Scheme 4).
For such a reaction of monohydroxythiazolidine 7,
which is the prototype of bishydroxythiazolidine 9, the
cyclization mechanism through the elimination of aniline
has been considered earlier.15 However, the case of
bishydroxythiazolidine 9 is more complicated than that of
its prototype 7 (see Scheme 4). For the latter, a structure
analogous to E contain phenyl substituents at both
N atoms of the isothioureido group, while in intermediꢀ
ate E derived from compound 9, one of these N atoms is
still bound to phenyl, while the other bears 3ꢀsubstituted
phenyl. Therefore, cyclization can be accompanied by
the elimination of either aniline (pathway a, leftꢀhand
side of structure E) or metaꢀsubstituted aniline (pathꢀ
way b, rightꢀhand side). If the cyclization followed only
pathway a, then elimination of two aniline molecules
would give rise to compound 11a. Pathway b would lead,
through elimination of 1,3ꢀdiaminobenzene, to two molꢀ
ecules of thiazolo[3,4ꢀa]quinoxaline 12a. If the cyclizaꢀ
tion in different moieties of structure E followed pathꢀ
ways a and b, only one aniline molecule would be reꢀ
leased to give thiazolo[3,4ꢀa]quinoxaline 12a and its
aminophenyl analog 13a.
These assumptions were confirmed experimentally. All
final products 11a, 12a, and 13a predicted for the reꢀ
action of bishydroxythiazolidine 9 with 1,2ꢀphenyleneꢀ
diamine were isolated. The last product was obꢀ
tained as Nꢀacetyl derivative 14a upon the acylation of

Synthesis of thiazolo[3,4ꢀa]quinoxalines
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 9, September, 2006
1673
Scheme 4
R = H (11a—14a), Me (11b—14b)

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Russ.Chem.Bull., Int.Ed., Vol. 55, No. 9, September, 2006
Mamedov et al.
The yield was 0.46 g (92%), m.p. 189—190 °C (cf. Ref. 37:
160—161 °C). Found (%): C, 63.38; H, 4.69; N, 14.66; S, 16.86.
1ꢀ(3ꢀaminophenylimino)thiazolo[3,4ꢀa]quinoxaline 13a
with acetic acid (solvent).
C
20H18N4S2. Calculated (%): C, 63.46; H, 4.79; N, 14.80;
The low yield of bis(thiazolo[3,4ꢀa]quinoxaline) 11a
suggests the predominant cyclization along pathway b.
Structure 11a was confirmed by MS data. In addition,
its 1H NMR spectrum shows a characteristic doublet
(δ 9.40, J = 7.9 Hz) for the H(9) proton of the thiazoꢀ
lo[3,4ꢀa]quinoxaline system23,24 and a signal for the carꢀ
bamoyl proton (δ 11.23). The major reaction product
(46%) was thiazoloquinoxaline 12a. Its spectroscopic
characteristics were identical with those of the compound
obtained earlier23,24 by a reaction of methyl 4ꢀhydroxyꢀ
3,5ꢀdiphenylꢀ2ꢀphenyliminothiazolidineꢀ4ꢀcarboxylate
with 1,2ꢀphenylenediamine. The structure of thiazoꢀ
lo[3,4ꢀa]quinoxaline 14a was confirmed by 1H NMR data.
Its spectrum contains the same signals as for comꢀ
pound 11a and additional singlets at δ 9.97 and 2.20 for
the NH and methyl protons, respectively, of the acetamido
group.
Finally, apart from products 11a—14a, we obtained
1,3ꢀbisthiazoline 10 in low yield because of dehydration
of compound 9, in contrast to the reaction of 1,2ꢀpheꢀ
nylenediamine with compound 7, which affords only
thiazolo[3,4ꢀa]quinoxaline 12a.23,25
A reaction of compound 9 with the more basic 4,5ꢀdiꢀ
methylꢀ1,2ꢀphenylenediamine generally proceeds like the
reaction with 1,2ꢀphenylenediamine. The exception was
that bis(thiazolo[3,4ꢀa]quinoxaline) 11b was the major
product (yield 43%), while thiazoloquinoxalines 12b
and 14b were only byꢀproducts.
S, 16.94. IR (Nujol), ν/cm–1: 3353, 3331, 3155, 2985, 1594,
1528, 1500, 1478, 1447, 1348, 1309, 1236, 1203, 1163, 1076,
869, 802, 761, 732, 691, 663, 627, 615. 1H NMR (DMSOꢀd6), δ:
7.12—7.49 (m, 13 H, 2 Ph + 3 H arom.); 7.69 (s, 1 H); 9.74, 9.88
(both s, 2 H each, 4 NH).
1,3ꢀBis(4ꢀhydroxyꢀ4ꢀmethoxycarbonylꢀ3,5ꢀdiphenylthiazolꢀ
idinꢀ2ꢀylideneamino)benzene (9). A. A mixture of 1,3ꢀbis(phenylꢀ
thioureido)benzene (0.5 g, 1.3 mmol) and sodium acetate (0.27 g,
3.3 mmol) in methanol (10 mL) was brought to boiling. A soluꢀ
tion of methyl chloro(phenyl)pyruvate (8) (0.59 g, 2.8 mmol) in
methanol (5 mL) was added dropwise to the resulting emulsion.
The reaction mixture was refluxed for 10 min, stirred at ~20 °C
for 10 h, and poured into cooled (5—10 °C) water (50 mL). The
precipitate that formed was filtered off, washed with water
(2×10 mL), and dried in air. Column chromatography on silica
gel gave yellowish white crystals. The yield of compound 9 was
0.91 g (94%), m.p. 109—111 °C, Rf 0.49 (CHCl3—AcOEt, 4 : 1).
Found (%): C, 65.55; H, 4.60; N, 7.44; S, 8.72. C40H34N4O6S2.
Calculated (%): C, 65.74; H, 4.69; N, 7.67; S, 8.77. IR (crystal),
ν/cm–1: 3468, 3356, 3059, 3030, 2951, 2924, 2852, 1743 (C=O),
1631 (C=N), 1586 (C=C arom.), 1535, 1493, 1452, 1402, 1322,
1253, 1117, 1028, 1002, 832, 762, 733, 696, 633, 606, 583, 563,
496. IR (Nujol), ν/cm–1: 3477 br (OH), 1743 (C=O), 1631
(C=N), 1585 (C=C arom.), 1530, 1493, 1325, 1257, 1142, 1118,
1076, 1028, 833, 765. IR (KBr), ν/cm–1: 3477 br (OH), 3348 br
(OH), 3059, 3029, 2951, 1743 (C=O), 1630 (C=N), 1586
(C=C arom.), 1538, 1493, 1452, 1322, 1253, 1142, 1117, 1027,
1
1002, 832, 762. MALDIꢀTOF MS, m/z: 731 [MH]+. H NMR
(DMSOꢀd6), δ: 3.12—3.23, 3.56—3.89 (s, no less than 10 and
20 lines, respectively, 6 H, 2 MeO); 5.05—5.11, 5.45—5.51 (s,
no less than 7 and 8 lines, respectively, 2 H, 2 CH); 6.67—7.48
(m, 24 H, 4 Ph + 4 H arom.).
Experimental
B. A solution of methyl chloro(phenyl)pyruvate (8) (0.59 g,
2.8 mmol) in CH2Cl2 (10 mL) was added dropwise at –15
to –20 °C to a mixture of 1,3ꢀbis(phenylthioureido)benzene
(0.5 g, 1.3 mmol) and sodium acetate (0.27 g, 3.3 mmol) in
CH2Cl2 (10 mL). The reaction mixture was stirred for 3 h,
warmed to ~20 °C, and washed with water (30 mL). The prodꢀ
uct was extracted with CH2Cl2 (2×15 mL). The extract was
dried with Na2SO4 and concentrated in vacuo approximately by
half to give colorless crystals. The yield was 0.29 g (58%), m.p.
114—116 °C.
Melting points were determined on a Boetius hot stage.
IR spectra were recorded on a Vectorꢀ22 FTIR spectrometer
(Bruker) in Nujol (compound 9) and in KBr pellets (9, 11b,
12a, and 14a,b) and on a JASCO FT/IRꢀ5000 spectrometer
in the crystal (9, 10, and 11a). Mass spectra (EI) were reꢀ
corded on a TRACE MS quadrupole mass spectrometer
(ThermoQuest/Finnigan) (direct inlet probe, water cooling).
MALDI mass spectra were recorded on a MALDI TOF
DYNAMO mass spectrometer (Finnigan) with pꢀnitroaniline as
a matrix. Elemental analysis was carried out on a CHNꢀ3 anaꢀ
The spectroscopic characteristics of compound 9 obtained
according to procedures A and B were identical.
1
lyzer. H NMR spectra were recorded in DMSOꢀd6 on Bruker
1,3ꢀBis(4ꢀmethoxycarbonylꢀ3,5ꢀdiphenylthiazolinꢀ2ꢀylideneꢀ
amino)benzene (10). A solution of SOCl2 (1.8 mL, 20 mmol) in
CHCl3 (5 mL) was added dropwise to a stirred solution of comꢀ
pound 9 (0.8 g, 1.1 mmol) in CHCl3 (10 mL). The reaction
mixture was refluxed for 1 h, turning intense red. Stirring was
continued at ~20 °C for an additional 20 h. The solvent and the
excess of SOCl2 were removed in vacuo. The resulting crystalline
substance was washed with water (3×15 mL) and dried in air.
The yield of compound 10 was 0.73 g (96%), colorless crystals,
m.p. 105—107 °C, Rf 0.20 (CHCl3—AcOEt, 5 : 1). Found (%):
C, 68.91; H, 4.19; N, 7.89; S, 9.15. C40H30N4O4S2. Calcuꢀ
lated (%): C, 69.15; H, 4.35; N, 8.06; S, 9.23. IR, ν/cm–1: 3053,
3016, 2943, 1729, 1620, 1574, 1487, 1435, 1348, 1274, 1199,
1166, 1074, 1022, 804, 759, 692, 609, 584. MALDIꢀTOF MS,
DRXꢀ500 (500.13 MHz) (for compounds 10 and 11a—14a) and
Bruker Avanceꢀ600 spectrometers (600.13 MHz) (for 9 and
11b—14b). Chemical shifts are given on the δ scale with referꢀ
ence to the residual signal of DMSO as the internal standard
(δ 2.54). Column chromatography was carried out on Silica
H
gel 60 (0.015—0.040 mm, Merck) and Silicagel L 100/160
(Chemapol). TLC was performed with Silica gel 60 F254 (Merck)
and Silufol plates. Methyl chloro(phenyl)pyruvate (8) was preꢀ
pared according to a known procedure.38
1,3ꢀBis(phenylthioureido)benzene. A solution of 1,3ꢀdiaminoꢀ
benzene (0.5 g, 4.6 mmol) and phenyl isothiocyanate (1.37 g,
10 mmol) in ethanol (20 mL) was stirred for 4 h. The crystals
that formed were filtered off and washed with ethanol (2×10 mL).

Synthesis of thiazolo[3,4ꢀa]quinoxalines
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 9, September, 2006
1675
m/z: 695 [MH]+. 1H NMR (DMSOꢀd6), δ: 3.46 (s, 6 H, 2 MeO);
6.98—7.57 (m, 24 H, 4 Ph + 4 H arom.).
(CHCl3—MeOH, 12 : 1). Found (%): C, 70.16; H, 4.24;
N, 11.38; S, 8.90. C42H32N6O2S2. Calculated (%): C, 70.37;
H, 4.50; N, 11.72; S, 8.94. IR, ν/cm–1: 3438, 3047, 2922, 2878,
1676, 1615, 1572, 1510, 1396, 1333, 1229, 1135, 1020, 877, 754,
692, 632, 590, 454. 1H NMR (DMSOꢀd6), δ: 2.25, 2.26 (both s,
6 H each, 4 Me); 6.84 (s, 1 H, H(2)); 6.88 (d, 2 H, H(4), H(6),
J = 7.6 Hz); 6.95 (s, 2 H, 2 H(6´)); 7.35 (dd, 4 H, 4 mꢀHPh, J =
7.54 Hz, J = 7.48 Hz); 7.40 (m, 3 H, H(5) + 2 pꢀHPh); 7.47 (d,
4 H, 4 oꢀHPh, J = 7.5 Hz); 9.24 (s, 2 H, 2 H(9´)); 11.14 (s,
2 H, 2 NH).
Reaction of bishydroxythiazolidine 9 with 1,2ꢀphenylenediꢀ
amine. 1,2ꢀPhenylenediamine (0.15 g, 1.4 mmol) was added to a
solution of compound 9 (0.5 g, 0.7 mmol) in acetic acid (15 mL).
The reaction mixture was refluxed for 15 min. The precipitate
that formed was filtered off, washed with AcOH (2×5 mL), and
dried to give compound 11a in the analytically pure state. The
filtrate was poured into water (50 mL) and the resulting solution
was treated with aqueous 5% KOH to pH ~6—7. The crystals
that formed were filtered off. Column chromatography in
CHCl3—AcOEt (10 : 1) gave products 12a, 14a, and 10. The
yield of the last product was 2—5%; its characteristics were
identical with those of the compound 10 obtained as described
above.
7,8ꢀDimethylꢀ3ꢀphenylꢀ1ꢀphenyliminoꢀ1Hꢀthiazolo[3,4ꢀa]ꢀ
quinoxalinꢀ4(5H )ꢀone (12b). The yield was 0.05 g (15%), yellow
crystals, m.p. 348—348.5 °C, Rf 0.67 (CHCl3—MeOH, 12 : 1).
Found (%): C, 72.35; H, 4.66; N, 10.42; S, 8.22. C24H19N3OS.
Calculated (%): C, 72.52; H, 4.82; N, 10.57; S, 8.07. IR, ν/cm–1
:
1,3ꢀBis(4ꢀoxoꢀ3ꢀphenylꢀ1H,5Hꢀthiazolo[3,4ꢀa]quinoxalinꢀ
1ꢀideneamino)benzene (11a). The yield was 0.05 g (11%), yellow
crystals, m.p. >360 °C, Rf 0.75 (CHCl3—AcOEt, 5 : 1).
Found (%): C, 69.31; H, 3.60; N, 12.83; S, 9.62. C38H24N6O2S2.
3443, 3195, 3048, 2969, 2937, 2878, 1684, 1612, 1576, 1514,
1485, 1442, 1389, 1337, 1216, 1148, 1020, 954, 863, 796, 773,
750, 741, 691, 633, 586, 502. H NMR (DMSOꢀd6), δ: 2.25 (s,
6 H, 2 Me); 6.96 (s, 1 H, H(6)); 7.12 (d, 2 H, 2 oꢀHPh, J =
7.8 Hz); 7.39—7.51 (m, 7 H, Ph + 2 mꢀHPh); 7.69 (d, 1 H,
H arom., J = 7.8 Hz); 9.25 (s, 1 H, H(9)); 11.14 (s, 1 H, NH).
MS, m/z (Irel (%)): 397 (100), 296 (35), 294 (93), 278 (32), 265
(38), 262 (29), 233 (41), 121 (79), 105 (61), 89 (21), 78 (25), 77
(80), 63 (33).
1
Calculated (%): C, 69.07; H, 3.66; N, 12.72; S, 9.70. IR, ν/cm–1
:
3183, 3127, 3047, 2981, 2898, 2773, 2703, 1674, 1633, 1605,
1566, 1490, 1477, 1437, 1393, 1334, 1316, 1265, 1217, 1139,
1092, 1075, 1048, 1033, 997, 962, 871, 804, 754, 740, 689, 658,
601, 551. MALDIꢀTOF MS, m/z: 661 [MH]+. 1H NMR
(DMSOꢀd6), δ: 6.82—7.44 (m, 20 H, 4 H arom. + 2 Ph + 6 H
of quinoxaline); 9.40 (d, 2 H, 2 H(9), J = 7.9 Hz); 11.23 (s,
2 H, 2 NH).
3ꢀPhenylꢀ1ꢀphenyliminoꢀ1Hꢀthiazolo[3,4ꢀa]quinoxalinꢀ
4(5H )ꢀone (12a). The yield was 0.11 g (46%), yellow crystals,
m.p. 300—301 °C (cf. Ref. 22: m.p. 300—300.5 °C), Rf 0.59
(CHCl3—AcOEt, 5 : 1). Found (%): C, 71.39; H, 4.15; N, 11.52;
S, 8.47. C22H15N3OS. Calculated (%): C, 71.52; H, 4.09;
N, 11.37; S, 8.68. IR, ν/cm–1: 3387, 3185, 3129, 1679, 1619,
1589, 1578, 1489, 1398, 1336, 1320, 1265, 1249, 1206, 1145,
1076, 1026, 806, 742, 690. 1H NMR (DMSOꢀd6), δ: 7.00—7.46
(m, 13 H, 2 Ph + 3 H of quinoxaline); 9.39 (d, 1 H, H(9), J =
7.4 Hz); 11.13 (s, 1 H, NH).
1ꢀ(3ꢀAcetylaminophenylimino)ꢀ3ꢀphenylꢀ1Hꢀthiazoꢀ
lo[3,4ꢀa]quinoxalinꢀ4(5H )ꢀone (14a). The yield was 0.012 g
(4%), dark yellow crystals, m.p. 286—289 °C, Rf 0.12
(CHCl3—AcOEt, 5 : 1). Found (%): C, 67.45; H, 4.15; N, 13.02;
S, 7.50. C24H18N4O2S. Calculated (%): C, 67.59; H, 4.25;
N, 13.14; S, 7.52. IR, ν/cm–1: 3358, 3169, 3075, 2905, 1694,
1668, 1608, 1595, 1557, 1463, 1403, 1307, 1289, 1250, 1225,
1151, 939, 927, 875, 833, 754, 731, 689, 602, 583, 545, 467.
1H NMR (DMSOꢀd6), δ: 2.20 (s, 3 H, Me); 7.00—7.46 (m,
12 H, Ph + 4 H arom. + 3 H of quinoxaline); 9.41 (d, 1 H, H(9),
J = 8.1 Hz); 9.97 (s, 1 H, MeCONH); 11.24 (s, 1 H, NH).
Reaction of bishydroxythiazolidine 9 with 4,5ꢀdimethylꢀ1,2ꢀ
phenylenediamine. A solution of compound 9 (0.5 g, 0.7 mmol)
and 4,5ꢀdimethylꢀ1,2ꢀphenylenediamine (0.19 g, 1.4 mmol) in
acetic acid (15 mL) was refluxed for 15 min. The precipitate that
formed was filtered off and washed with AcOH (2×5 mL) to give
compound 11b. The filtrate was poured into water (30 mL) and
the resulting solution was treated with aqueous 5% KOH to
pH ~6—7. The crystals that formed were filtered off. Column
chromatography in CHCl3—MeOH (15 : 1) gave products 12b,
14b, and 10.
1ꢀ(3ꢀAcetylaminophenylimino)ꢀ7,8ꢀdimethylꢀ3ꢀphenylꢀ1Hꢀ
thiazolo[3,4ꢀa]quinoxalinꢀ4(5H )ꢀone (14b). The yield was 0.01 g
(3%), m.p. 339—341 °C, Rf 0.55 (CHCl3—MeOH, 12 : 1).
Found (%): C, 68.46; H, 4.69; N, 12.20; S, 6.95. C26H22N4O2S.
Calculated (%): C, 68.70; H, 4.88; N, 12.33; S, 7.05. IR, ν/cm–1
:
3359, 3179, 3078, 2915, 1660, 1638, 1617, 1592, 1509, 1489,
1389, 1356, 1294, 1235, 1203, 1149, 1085, 1063, 1025, 891, 870,
815, 766, 695, 646, 625, 581, 546, 496. 1H NMR (DMSOꢀd6), δ:
2.19 (s, 6 H, 2 Me); 2.58 (s, 3 H, MeCONH); 6.86 (s, 1 H,
H(6)); 6.99 (d, 2 H, 2 oꢀHPh, J = 7.8 Hz); 7.10 (t, 1 H, pꢀHPh
,
J = 6.8 Hz); 7.23 (br.s, 1 H, MeCONH); 7.30—7.37 (m, 4 H,
2 H arom. + 2 mꢀHPh); 7.69 (d, 2 H, 2 H arom., J = 7.8 Hz);
8.32 (s, 1 H, H(9)); 10.83 (s, 1 H, NH). MS, m/z (Irel (%)):
647 (18), 455 (12), 454 (36), 295 (19), 294 (100), 265 (9),
121 (36), 77 (9).
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Received April 19, 2006;
in revised form July 14, 2006