Fused polycyclic nitrogen-containing heterocycles 21. Condensation of 4-hydroxy-3,5-diphenyl-2-phenyliminothiazolidine with 5-fluoro-4-morpholino- and 4-(4-methylpiperazino)-1,2-phenylenediamines

Article abstract of DOI:10.1007/s11172-009-0030-6

The condensation of 4-hydroxy-3,5-diphenyl-2-phenyliminothiazolidine with 5-fluoro-4-morpholino- and 5-fluoro-4-(4-methylpiperazino)-1,2-phenylenediamines leads to region-isomeric thiazolo[3,4-a]quinoxalines differing in substituents in positions 7 and 8

Full text of DOI:10.1007/s11172-009-0030-6

Russian Chemical Bulletin, International Edition, Vol. 58, No. 1, pp. 203—211, January, 2009
203
Fused polycyclic nitrogenꢀcontaining heterocycles
21.* Condensation of 4ꢀhydroxyꢀ3,5ꢀdiphenylꢀ2ꢀphenyliminothiazolidine
with 5ꢀfluoroꢀ4ꢀmorpholinoꢀ and ꢀ4ꢀ(4ꢀmethylpiperazino)ꢀ1,2ꢀphenylenediamines**
V. A. Mamedov,a N. A. Zhukova,a T. N. Beschastnova,a A. A. Balandina,a
A. T. Gubaidullin,a S. K. Kotovskaya,b Sh. K. Latypov,a Ya. A. Levin,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.knc.ru
bUral State Technical University,
19 ul. Mira, 620002 Ekaterinburg, Russian Federation.
Fax: +7 (343 2) 74 0458. Eꢀmail: kotovskaya@mail.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@ios.uran.ru
The condensation of 4ꢀhydroxyꢀ3,5ꢀdiphenylꢀ2ꢀphenyliminothiazolidine with 5ꢀfluoroꢀ
4ꢀmorpholinoꢀ and 5ꢀfluoroꢀ4ꢀ(4ꢀmethylpiperazino)ꢀ1,2ꢀphenylenediamines leads to regioꢀ
isomeric thiazolo[3,4ꢀa]quinoxalines differing in substituents in positions 7 and 8 of the
benzene ring. From the ratio of isomers formed it follows that the mesomeric effect of a fluorine
atom in 1,2ꢀphenylenediamines is comparable with the influence of an aminosubstituent.
Key words: 4ꢀhydroxyꢀ3,5ꢀdiphenylꢀ2ꢀphenyliminothiazolidine, cyclocondensation,
thiazolo[3,4ꢀa]quinoxalines, IR spectroscopy, NMR spectroscopy, Xꢀray diffraction analysis.
Scheme 1
Quinoxalines as well as fused systems based on them
represent fragments of many biologically active comꢀ
pounds and drugs.2—13 Among cyclizations accompanied
by the formation of azolo[3,4ꢀa]quinoxalines, the reacꢀ
tions of 4ꢀhydroxyꢀ2ꢀiminothiazolidines with 1,2ꢀpheꢀ
nylenediamines studied by us earlier14—18 occupy an
important place. In order to develop this approach as
applied to the synthesis of fluorineꢀcontaining thiazoloꢀ
[3,4ꢀa]quinoxalines that are prospective as potential
biologically active compounds, in the present work we
studied the condensation of 4ꢀhydroxyꢀ3,5ꢀdiphenylꢀ
2ꢀphenyliminothiazolidine 1 with 5ꢀfluoroꢀ4ꢀmorpholinoꢀ
and 5ꢀfluoroꢀ4ꢀ(4ꢀmethylpiperazino)ꢀ1,2ꢀphenyleneꢀ
diamines (2a,b, respectively).
The use of “nonsymmetrically” substituted 1,2ꢀpheꢀ
nylenediamines 2a,b in this reaction (see Ref. 1) results in
the formation of a mixture of two isomeric thiazoloꢀ
quinoxalones 3a,b and 4a,b in the ratio 2 : 3 with 7ꢀfluoroꢀ
derivatives 4a,b prevailing in both cases (Scheme 1). The
isomers were separated by column chromatography.
* For part 20, see Ref. 1.
R =
(a),
(b)
** Dedicated to Academician A. I. Konovalov on his 75th birthday.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 201—209, January, 2009.
1066ꢀ5285/09/5801ꢀ0203 © 2009 Springer Science+Business Media, Inc.

204
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Mamedov et al.
The structures of thiazoloquinoxalones were established
thiazolo[3,4ꢀa]quinoxaline 4a was examined in detail,
whereas the structure of the other compounds was
deduced by analogy.
1
on the basis of H and 13C NMR spectral data and Xꢀray
diffraction analysis.
1
A pecularity of the H NMR spectra of compounds
The 1H NMR spectrum of compound 4a in DMSOꢀd6
at 323 K consists of a broadened signal of the NH proton
(δ 11.08), two doublet signals (δ 9.42 and 6.93) and a
number of lines in the region with δ 7.5—7.1 and 3.8—2.8.
The 13C NMR spectrum contains signals in the area with
δ 154—150 and δ 134—102 and also two signals at δ 65.87
and 50.59, a portion of the signals is split due to spinꢀspin
coupling with the fluorine atom. With the aid of the
2D COSY method, three spin systems relating to the
protons of the two phenyl moieties and a morpholine ring
have been distinguished. Two doublet signals (δ 9.42 and
6.93) for which correlations in the COSY spectrum were
not detected, correspond to the protons H(6)/H(9) or
H(9)/H(6). Taking into account 2D HSQC spectral data,
the signals for all the carbon atoms of compound 4a,
which are bound to protons, were determined.
3a,b and 4a,b is the presence of a diagnostic signal of the
proton H(9), which appears as a doublet with the spinꢀ
spin coupling constant equal to 8.9 or 15.6 Hz. Since
J = 15.6 Hz corresponds to the vicinal coupling constant
3JH,F (see Ref. 19), the major isomers can be identified as
compounds 4a,b, while the minor isomers can be identiꢀ
fied as compounds 3a,b. The signals for the protons H(6)
resonate in higher fields, apparently, due to the influence
of the electronꢀdonating morpholine and piperazine
substituents. A more comprehensive substantiation of
these assignments is given below.
The structure of isomeric 7,8ꢀsubstituted thiazoloꢀ
[3,4ꢀa]quinoxalines 3a, 4a and 3b, 4b was established
based on a series of correlation experiments 2D NMR
(COSY, HSQC, HMBC),20,21 whereby the structure of
H(2″)/(4″)/(6″)
H(3´)/(4´)/(5´)
H(2m)/(6m)
H(3m)/(5m)
H(3″)/(5″)
H(2´)/(6´)
NH
H(9)
H(6)
δ
C(6)
C(9)
NH/C(6)
105
110
115
120
125
130
135
140
145
150
a
H(4″)/C(2″)/(6″)
H(2´)/(6´)/C(3)
C(2″)/(6″)
C(3a)
C(9a)
C(5a)
H(6)/С(9a)
NH/C(3a)
H(9)/С(5a)
H(6)/C(5a)
H(6)/C(8)
H(2m)/(6m)/C(8)
C(1´)
H(9)/С(8)
C(8)
H(3´)/(5´)/C(1´)
H(3″)/(5″)/C(1″)
H(6)/С(7)
C(1″)
С(7)
С(4)
H(9)/С(7)
NH/C(4)
H(2″)/(6″)/C(1)
C(1)
H(9)/Ν(1m)
H(3m)/(5m)/N(1m)
H(6)/Ν(1m)
H(6)/N(5)
100
150
200
b
H(9)/Ν(10)
H(2″)/(6″)/N(1″)
11
10
9
8
7
6
5
4
δ
1
Fig. 1. Fragments of the 2D HMBC 1H—13C (a) and 2D HMBC Н—15N (b) spectra of compound 4a.

Condensation of hydroxyphenyliminothiazolidine
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 1, January, 2009
205
1
Ultimately, the structure of the molecule was estabꢀ
In the 2D HMBC Н—13С spectrum (see Fig. 1, a),
crossꢀpeaks of different intensities between the protons
Н(6), Н(9) and the carbon atom C(7) (δ 151.08) with
JF,C = 244.5 Hz (see Ref. 22) are observed. Among them
the peak from the proton Н(9) is the most intensive,
which makes it possible to assign this carbon atom as С(7)
1
lished on the basis of 2D HMBC H—13C, 2D HSQC
1
1H—15N, and HMBC H—15N methods (Figs 1 and 2).
The principal HMBCꢀcorrelations demonstrating the
connectivities between fragments in molecule 4a are as
follows (see Fig. 2): between H(2´)/H(6´) and C(3),
between H(2")/H(6") and N(1"), between Н(2")/H(6")
and C(1) (the attachment of the Ph´ and Ph´´ groups
to the thiazole ring, respectively). In the 2D HMBC
1H—15N spectrum these are between C(3m)H2/C(5m)H2
and N(1m) (the structure of the morpholine ring).
3
2,4
since JС,Н
>
J
. Therefore, it has been established
that the fluorine atom in compound 4a is attached to
the atom С(7). In addition, in the HMBC Н—13С
spectrum (see Fig. 1, a) a crossꢀpeak between the protons
С(2m)Н2/C(6m)Н2 and the atom С(8) is present, which
suggests the presence of a covalent bond between the
morpholine ring and the benzene ring of the quinoxaline
system, the morpholine residue being bound to the atom
С(8). Also, in the HMBC 1Н—13С spectrum (see Fig. 1, a)
there are correlations between the NH protons and the
С,Н
1
The positions of substituents in the benzene ring of
the quinoxaline system were determined in the following
1
way. In the HMBC H—13C spectrum (see Fig. 1, a), a
correlation between the NH proton and the C atom of a
2,4
CH group (δ 102.64) is observed; given that 3JС,Н
>
J
С,Н
(hence, the corresponding crossꢀpeak is more intensive22),
this peak was assigned to the atom С(6). This allowed the
differentiation of the atoms С(6) and С(9) and the assignꢀ
ment of the corresponding protons Н(6) and Н(9).
15N NMR data for compound 4a additionally support the
assignment of the proton Н(6): in the 2D HMBC
1H—15N spectrum (see Fig. 1, b) a crossꢀpeak between
the atom N(5) (the signal of which was determined from
the 2D HSQC 1Н—15N spectrum) and the proton Н(6) is
present, whereas for the proton Н(9) there is no such a
peak (3JN,Н > 4JN,Н).
δcalc
a
С(3)
140
R2 = 0.9665
120
100
80
60
40
60
80
100
120
140 δexp
δcalc
240
200
160
120
80
R2 = 0.9978
b
40
60
100
140
180
220 δexp
Fig. 2. Basic HMBCꢀcorrelations from protons to carbon atoms
(thin arrows) and nitrogen atoms (thick arrows) for compounds
3a and 4a.
Fig. 3. The correlation of calculated (δcalc) and experimental
(δexp) chemical shifts 13С (а) and 15N (b) for compound 4a.

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Russ.Chem.Bull., Int.Ed., Vol. 58, No. 1, January, 2009
Mamedov et al.
Fig. 4. Basic HMBCꢀcorrelations from protons to carbon atoms for compounds 3b and 4b.
atoms С(3а) and С(4), between Н(6) and С(9а), Н(9)
and С(5а), and in the 2D HMBC 1H—15N spectrum (see
Fig. 1, b) they are between the proton Н(9) and the atom
N(10), which eventually enables the determination of the
complete structure of quinoxaline 4a.
(for all 13С), R2 = 0.994 (without С(3)). For the resonance
signals of the nitrogen atom a virtually ideal agreement
with the theory is observed (R2 = 0.998). The calculated
chemical shifts of Н also correlate well with experimenꢀ
tal ones: R2 = 0.975.
1
Accordingly, based on the data from a series of
Analogously, the structure of thiazolo[3,4ꢀa]quinoxꢀ
alines 3a,b and 4b was determined (Figs 2 and 4). In
addition, the structures of compounds 3b and 4a were
confirmed by the results of Xꢀray diffraction analyses
(Figs 5 and 6).
Both compounds crystallize with incorporation of
DMSO molecules in the ratio of 1 : 1, and in the crystal
of compound 4a the solvate molecule is disordered over
two positions with a 0.87 : 0.13 occupancy ratio.
The planarity of the tricyclic fragment of thiazoloꢀ
[3,4ꢀa]quinoxalines in crystals is disturbed. Thus in the
tricyclic portion of molecule 3b the planes of the thiazole
ring and the fused benzene fragment constitute a dihedral
angle equal to 6.7(1)°, in which the planes of the benzene
and thiazole ring deviate in the same direction from the
plane of the nitrogenꢀcontaining heterocycle with angles
1
2Dꢀheterocorrelation experiments (1Н—13С и H—15N)
the structure of compound 4а has unambiguously been
established.
With the aim of the evaluation of the potential of
theoretical methods for the determination of NMRꢀ
parameters, in this work the calculation of the chemical
1
shifts of Н, 13С, and 15N (GIAO B3LYP/6ꢀ31G(d)//
HF/6ꢀ31G) has been carried out for compound 4a (corꢀ
relation plots for 13С and 15N are depicted in Fig. 3).
Making allowance for the underestimation of the chemiꢀ
cal shifts of 13С which is characterstic for this computaꢀ
tional method (see Refs 23—26), and a marked27,28 deviaꢀ
tion of the chemical shift of 13С vicinal to atoms of the
third period (P, S, Cl), on the whole, good agreement of
theoretical and experimental data is observed (R2 = 0.967
C(13)
C(14)
C(15)
C(14)
C(12)
C(15)
C(11)
N(11)
F(8)
C(13)
C(16)
C(11)
N(1)
C(16)
S(2)
C(75)
C(76)
C(8)
C(83)
O(84)
C(1)
C(12)
N(71)
C(7)
C(77)
N(74)
C(73)
C(9A)
C(82)
C(9)
C(6)
C(1)
S(2)
N(81)
C(8)
C(9)
C(3)
C(31)
N(10)
N(5)
N(10)
C(3)
C(31)
C(32)
C(33)
C(85)
C(86)
C(36)
C(5A)
C(72)
C(9A)
C(3A)
C(4)
C(36)
C(5A)
C(3A)
C(4)
C(35)
C(34)
C(7)
C(32)
F(7)
C(6)
N(5)
C(34)
O(4)
C(42)
C(35)
C(33)
C(52)
O(4)
O(50)
S(50)
O(22)
S(22)
C(41)
C(51)
Fig. 5. The geometry of a molecule of compound 3b in the
crystal. Nonꢀhydrogen atoms are represented with probability
ellipsoids of thermal vibrations (p = 50%), hydrogen atoms are
depicted as spheres of an arbitrary radius.
Fig. 6. The geometry of a molecule 4a in the crystal. A disorꢀ
dered DMSO molecule is shown in the position with higher
occupancy.

Condensation of hydroxyphenyliminothiazolidine
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 1, January, 2009
207
of 4.3(1) and 4.7(1)°, respectively. Even more appreciable
deviations are observed in the molecule of compound
4a, whose tricyclic fragment proves to be “twisted” (the
torsion angle C(1)—N(10)—C(9A)—C(9) amounts to
9.2(4)°), while the planes of the thiazole ring and the
fused benzene fragment form a dihedral angle of 10.2(1)°.
Such distortions of the tricyclic system seem to be assoꢀ
ciated with the presence of bulky substituents in the
orthoꢀpositions of the fused benzene fragment of the
molecules since they are absent in thiazolo[3,4ꢀa] quinoxꢀ
alines with small substituents in the benzene moiety.
In molecule 4a (see Fig. 6), the morpholine substituꢀ
ent is somewhat turned relative to the benzene fragment
of the molecule (the average plane of the substituent conꢀ
stitute a dihedral angle of 36.3(1)° with the plane of the
fused benzene ring). The planes of the phenyl sunstituents
С(11)—С(16) and С(31)—С(36) constitute dihedral
angles with the plane of the thiazole ring, which amount
to 57.2(1) and 64.4(1)°, respectively. Virtually the same
arrangement of substituents is also observed in molecule
3b (see Fig. 5).
Interactions of the π—πꢀtype in crystals of the studied
compounds were analyzed by using formal criteria of the
existence of π—πꢀinteractions29 and also literature data.30
In the crystals of compound 3b, the stacking effect is
observed: on account of interactions of electron systems
the triacyclic fragments of thiazolo[3,4ꢀa]quinoxaline
make up sloping piles along the axis 0a with two distances
alternating in the piles 3.58 and 3.92 Å between rootꢀ
meanꢀsquare planes of molecules arranged according to
the “headꢀtoꢀtail” type (Fig. 7, a). As a result of packing
of such piles according to the hexagonal type and the
presence of bulky substituents, the solvate DMSO
molecules are pairwise isolated in the crystal by surroundꢀ
ing molecules of thiazolo[3,4ꢀa]quinoxaline. The inconꢀ
venience of mutual packing of bulky substituents also
accounts for a low value of the calculated packing coefꢀ
ficient of molecules, 66.3%.
Scheme 2
As has been observed earlier,1 in the crystals of
thiazolo[3,4ꢀa]quinoxalines 3b and 4a the solvate molꢀ
ecule of DMSO prevents the formation of an Нꢀdimer of
molecules owing to the creation of classical hydrogen
bonds and itself forms a hydrogen bond between the
sulfinyl group of the DMSO molecule and the hydrogen
atom of the amide group. The parameters of the hydrogen
bond in the crystal of compound 3b are as follows: the
bond H(5)...O(22), 1.93 Å; N(5)...O(22), 2.783(4) Å; the
angle N(5)—H(5)...O(22), 169°; in the crystals of comꢀ
pound 4a: the bond H(5)...O(50), 1.73 Å; N(5)...O(50),
2.775(3) Å, the angle N(5)—H(5)...O(50), 165°.
a
b
Fig. 7. a. A fragment of the packing of molecules in the crystal of compound 4a (a projection along the axis 0b); DMSO molecules are
not shown. b. The formation of zigzag chains by DMSO molecules in the crystal 4a (a projection along the axis 0b); the DMSO
molecules are depicted as large spheres.

208
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 1, January, 2009
Mamedov et al.
Scheme 3
Scheme 4
The molecules of thiazoloquinoxaline 4a form dimers
in crystals owing to π—πꢀinteractions between the aromatic
systems of the triacyclic fragments of the molecules (the
distance between the arbitrary centers of the triacyclic
systems of the molecules is 4.63 Å, the dihedral angle
between their rootꢀmeanꢀsquare planes is 0°, the shortest

Condensation of hydroxyphenyliminothiazolidine
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 1, January, 2009
209
8ꢀFluoroꢀ7ꢀmorpholinoꢀ3ꢀphenylꢀ1ꢀphenyliminothiazolo[3,4ꢀа]ꢀ
quinoxalinꢀ4(5H)ꢀone (3а) and 7ꢀfluoroꢀ8ꢀmorpholinoꢀ3ꢀphenylꢀ
1ꢀphenyliminothiazolo[3,4ꢀа]quinoxalinꢀ4(5H)ꢀone (4а) (a
mixture of isomers 3а + 4а, 40 : 60). To a solution of 0.5 g
(2.07 mmol) 1ꢀaminoꢀ5ꢀfluoroꢀ4ꢀmorpholinoꢀ2ꢀnitrobenzene in
30 mL of anhydrous ethanol 96% hydrazine (0.6 mL, 18.9 mmol)
was added. The reaction mixture was heated on a water bath
until complete dissolution of the precipitate, after which it was
cooled to 30 °С, a catalyst (RaneyꢀNi)32 (0.1 g) in 20 mL of
anhydrous ethanol was added, and the mixture was refluxed for
6 h. The reaction mixture was cooled to room temperature, the
catalyst was filtered off, and the solvent was evaporated in vacuo.
To a solution of thus prepared diamine 2a in AcOH (30 mL) was
added 4ꢀhydroxythiazolidine 1 (0.83 g, 2.14 mmol). The mixꢀ
ture was refluxed for 5 h, cooled, and acidified with 5% HCl.
The mustardꢀcolored precipitate that formed was filtered
off and recrystallized from CH3CN to give a mixture of 3а and
4а (0.85 g, 87%), m.p. 239—241 °С. The separation of the
isomers was carried out by column chromatography on Kieselgel
(chloroform—hexane, 6 : 4). Rf values are given for a fixed layer
of SiO2 (Silufol) in a chloroform—hexane—methanol (6 : 4 : 1)
system. The yield of compound 3а is 0.03 g (4%), yellowꢀ
colored crystals, Rf 0.45, m.p. 331—335 °С. Found (%): С,
65.74; H, 4.22; N, 11.61; S, 6.65. С26H21FN4O2S. Calculated
distance between these planes is 3.46 Å). The molecules
of the dimer, in turn, are connected with each other by a
combination of interactions of different types (С—Н...π,
С—H...O, С—H...F) in a threeꢀdimensional network of
hydrogenꢀbonded molecules. In this network in a crystal,
pseudochannels parallel to the axis 0b are formed in which
the solvate DMSO molecules disordered over two sites
are located (see Fig. 7, b). Despite the fact that according
to the calculations there are no cavities potentially accesꢀ
sible to additional solvent molecules in the crystal, the
packing coefficient of molecules in the crystal turns out to
be extremely low, 65.2%.
The reasons for the observed ratio of isomeric prodꢀ
ucts in the investigated coupling of diamines 2а,b in favor
of the preferential formation of 7ꢀfluroderivatives 4a,b are
the same as those established earlier1 for the reaction of
4ꢀmethylꢀ and 4ꢀnitroꢀ1,2ꢀphenylenediamines (taking
into consideration that the reaction was carried out in
acetic acid). The protonation of the nitrogen atoms of the
morpholine and piperazine substituents in 4ꢀsubstituted
1,2ꢀphenylenediamines 2a,b decreases the electronꢀ
donating properties of the amino group. The mesomeric
effect of a fluorine atom is comparable to the effect of an
ammonium group.
(%): С, 65.95; Н, 4.30; N, 11.56; S, 6.72. IR (Nujol), ν/cm–1
:
2930—2855 (NH), 1674 (С=О), 1615 (C=N), 1587, 1514.
1Н NMR, δ: 3.00—3.02 (m, Н, N(СН2)2); 3.74—3.76 (m, 4 Н,
О(СН2)2); 6.82 (d, 1 Н, Н(6), J = 8.7 Hz); 7.07—7.14 (m, 3 Н,
2 oꢀH + pꢀH of phenylimine); 7.33—7.36 (m, 3 Н, 2 oꢀH + pꢀHPh);
7.40 (d.d, 2 Н, 2 mꢀH of phenylimine, J = 7.7 Hz, J = 7.7 Hz);
7.42—7.46 (m, 2 Н, 2 mꢀHPh); 9.26 (d, 1 Н, Н(9), JH,F = 15.9 Hz);
11.03 (s, 1 Н, NH). The yield of compound 4а is 0.43 g (50%),
yellowꢀcolored crystals, Rf 0.62, m.p. 281—282 °С. Found (%):
С, 65.74; H, 4.22; N, 11.61; S, 6.65. С26H21FN4O2S. Calcuꢀ
lated (%): С, 66.09; Н, 4.48; N, 11.86; S, 6.78. IR (Nujol),
ν/cm–1: 2953—2854 (NH), 1667 (С=О), 1616 (C=N), 1589,
Of three possible variants of the first step of the reacꢀ
tion,15—17 viz., amidation or imination involving cyclic
tautomers αꢀ1, βꢀ1 or imination of openꢀchain tautomer 5
(Scheme 2), we give preference to the latter option, which
most probably demonstrates the formation of the 3аꢀhydroxyꢀ
thiazoloquinoxalines isolated earlier1,18 and characterized
as intermediate compounds (Schemes 3 and 4).
1
1514. Н NMR, δ: 2.94—2.96 (m, 4 Н, N(СН2)2); 3.72—3.74
Experimental
(m, 4 Н, О(СН2)2); 6.92 (d, 1 Н, Н(6), JH,F = 12.6 Hz);
7.12—7.15 (m, 3 Н, 2 oꢀH + pꢀH of phenylimine); 7.35—7.37
(m, 3 Н, 2 oꢀHPh + pꢀHPh); 7.42 (d.d, 2 Н, 2 mꢀH of phenylꢀ
imine, J = 7.7 Hz, J = 8.1 Hz); 7.45—7.47 (m, 2 Н, 2 mꢀHPh);
9.42 (d, 1 Н, Н(9), J = 9.0 Hz); 11.15 (s, 1 Н, NH).
The NMR spectra were recorded on a BrukerꢀAVANCEꢀ600
spectrometer (600 (1Н), 150.926 (13С) and 60.796 MHz (15N))
at 30 °С in DMSOꢀd6 (for compounds 3а and 4а) and CDCl3
(for compounds 3b and 4b). The residual signal of CDCl3
(δН 7.26, δС 77.00) or DMSO (δН 2.50, δС 39.43) was used as the
internal standard. Chemical shifts in the 15N NMR spectra were
measured relative to the signal of an external standard CD3CN
(δ 0). The IR spectra were measured on a Vectorꢀ22 FTIR
spNectrometer (Bruker) in KBr pellets. Melting points were
determined on a Boetius heating stage. 4ꢀHydroxyꢀ4ꢀmethoxyꢀ
carbonylꢀ3,5ꢀdiphenylꢀ2ꢀphenyliminothiazolidine (1) was
obtained by the reaction of methyl 3ꢀchloroꢀ2ꢀoxoꢀ3ꢀphenylꢀ
propionate with N,N´ꢀdiphenylthiocarbamide using a procedure
developed by us earlier.31
The study of compounds by 1H NMR spectroscopy was
performed at the NMR Department of the Federal Collective
Spectral Analytical Center of Physicochemical Research of
Structure, Propeties, and Composition of Compounds and
Materials and the Federal Center of Collective Use for Physiꢀ
cochemical Research of Compounds and Materials with support from
the Ministry of Education and Science of the Russian Federaꢀ
tion (State Contract Nos 02.451.11.7036 and 02.451.11.7019).
8ꢀFluoroꢀ7ꢀ(4ꢀmetylpiperazino)ꢀ3ꢀphenylꢀ1ꢀphenyliminoꢀ
thiazolo[3,4ꢀа]quinoxalinꢀ4(5Н)ꢀone (3b) and 7ꢀfluoroꢀ8ꢀ
(4ꢀmetylpiperazino)ꢀ3ꢀphenylꢀ1ꢀphenyliminothiazolo[3,4ꢀа]ꢀ
quinoxalinꢀ4(5Н)ꢀone (4b) (a mixture of isomers 3b + 4b in a
ratio of 26 : 74). The reduction of 0.5 g (1.97 mmol) of 5ꢀfluoroꢀ
1ꢀaminoꢀ4ꢀ(4ꢀmethylpiperazino)ꢀ2ꢀnitrobenzene in 40 mL of
anhydrous ethanol with hydrazine (0.6 mL, 18.9 mmol) and
RaneyꢀNi (0.1 g) in 20 mL of anhydrous ethanol was carried out
as described above (3 h). The reaction mixture was cooled to
room temperature, the catalyst was filtered off, and the solvent
was evaporated in vacuo. A solution of thus prepared diamine
2b and 4ꢀhydroxythiazolidine 1 (0.79 g, 2.04 mmol) in AcOH
(30 mL) was refluxed for 3 h. The solvent was evaporated, the
residue was triturated with ether. The dark greenꢀcolored preꢀ
cipitate that formed was filtered off to give a mixture of 3b + 4b
(0.63 g, 69%) with m.p. 251—256 °С. The separation of the
isomers was carried out by column chromatography on Kieselgel
(chloroform—hexane, 4 : 1). Rf values are given for a fixed layer
of SiO2 (Silufol) in the system chloroform—hexane—methanol

210
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 1, January, 2009
Mamedov et al.
(1 : 1 : 6). The yield of compound 3b is 0.11 g (17%), yellowꢀ
colored crystals, Rf 0.18, m.p. 309—310 °С. Found (%): С, 66.77;
H, 5.10; N, 14.36; S, 6.45. С27H24FN5OS. Calculated (%):
С, 66.79; Н, 4.98; N, 14.42; S, 6.60. IR, ν/cm–1: 3200—2700
out by using the MolEN software33 on an AlphaStation 200
computer. No drop of intensities of three test reflections over
the time of experiments was observed. The absorption was taken
into account empirically. All the structures were solved by the
direct method based on the SIR software34 and were refined first
in the isotropic and then anisotropic approximation with the use
of the SHELXLꢀ97 (Ref. 35) and WinGX (Ref. 36) software.
The hydrogen atoms of amino groups were determined from
difference series of electron density (the positions of the other
hydrogen atoms were calculated on the basis of stereochemical
criteria) and refined by the corresponding riding models. The
analysis of intermolecular interactions and images was performed
using the PLATON software.29
1
(NH), 1675 (C=O), 1617 (C=N), 1590. Н NMR, δ: 1.25 (s,
3 Н, Me); 2.41—3.05 (m, 8 Н, 4 СН2); 6.33 (d, 1 Н, Н(6),
J = 7.6 Hz); 7.07—7.47 (m, 10 Н, 2 Ph); 9.38 (d, 1 Н, Н(9),
JH,F = 15.4 Hz); 9.55 (s, 1 Н, NH). The yield of compound 4b is
0.30 g (48%), yellowꢀcolored crystals, Rf 0.34, m.p. 275—280 °С.
Found (%): С, 66.82; H, 4.92; N, 14.44; S, 6.50. С27H24FN5OS.
Calculated (%): С, 66.79; Н, 4.98; N, 14.42; S, 6.60. IR, ν/cm–1
:
1
3200—2700 (NH), 1681 (C=O), 1614 (C=N), 1582. Н NMR,
δ: 1.26 (s, 3 Н, Me); 2.58—3.30 (m, 8 Н, 4 СН2); 6.53 (d, 1 Н,
Н(6), JH,F = 12.0 Hz); 7.09—7.44 (m, 10 Н, 2 Ph); 9.47 (d, 1 Н,
Н(9), J = 8.8 Hz); 10.33 (s, 1 Н, NH).
The atomic coordinates of structures 3b and 4a and their
temperature parameters were deposited with the Cambridge
Crystallographic Data Centre (http://www.ccdc.cam.ac.uk; the
deposition numbers are CCDC 671 885 and 671 886, respecꢀ
tively).
The Xꢀray diffraction analysis of single crystals of compounds
3b, 4а was conducted at the Department of Xꢀray Diffraction
Research of the Center of Collective Use based on the laboraꢀ
tory of Xꢀray diffraction research methods of the A. E. Arbuzov
Institute of Organic and Physical Chemistry, Kazan Research
Center of the Russian Academy of Sciences. The Xꢀray diffracꢀ
tion characteristics of compounds, experiment parameters and
structure refinements are given in Table 1. The experiments
were perfomed on an automatic fourꢀcircle CADꢀ4 diffracꢀ
tometer (NONIUS B.V.) at 20 °С (graphite monochromator,
CuꢀКα radiation), preliminary data processing was carried
Sh. K. Latypov expresses his thanks to the National
Science Support Foundation (a grant for young Doctors
of Sciences).
This work was financially supported by the Russian
Foundation for Basic Research (Project Nos 07ꢀ03ꢀ00613ꢀа
and 05ꢀ03ꢀ33008ꢀа), the Council on Grants of the President
of the Russian Federation (State program for the Support
of Leading Scientific Schools of the Russian Federation,
grant NShꢀ3758.2008.3), and the Federal Target Program
“Research and Development in the Priority Progress
Directions of the Scientific and Technical Complex of
Russia for 2007—2012” (State contract 02.512.11.2237).
Table 1. The parameters of the crystals of compounds 3b, 4а and
conditions of the Xꢀray experiment
Parameter
3b
4a
Color, habitus
Yellow (prismatic form)
Molecular formula
C
27H24FN5OS• C26H21FN4O2S•
References
•C2H6OS
563.70
•C2H6OS
550.66
Molecular weight
Crystal system
Space group
a/Å
b/Å
c/Å
Triclinic
Monoclinic
P21/n
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Recieved June 3, 2008;
in revised form September 22, 2008