Fused Nitrogen-Containing Heterocycles: IV. 3-Benzoyl-2-oxo-1,2- dihydroquinoxaline Hydrazones and Flavazoles Derived Therefrom

Article abstract of DOI:10.1023/A:1023415301274

3-Benzoyl-1,2-dihydroquinoxalin-2-one reacts with hydrazine and thiosemicarbazide to give the corresponding hydrazone and thiosemicarbazone. The reaction with arylhydrazines yields 3-(α-arylazobenzylidene)-1,2,3,4- tetrahydroquinoxalin-2-ones which are tautomeric to the respective arylhydrazones. On heating in boiling acetic acid, the products of both types undergo intramolecular cyclocondensation with formation of 3-phenylpyrazolo[3,4- b]quinoxalines (3-phenylflavazoles). 3-Benzoyl-1,2-dihydroquinoxalin-2-one thiosemicarbazone gives rise to flavazole structure only in the presence of methyl 3-chloro-2-oxo-3-phenylpropionate as a trap of thiocarbamoyl moiety. The cyclization of 3-(α-hydrazonobenzyl)-1,2-dihydroquinoxalin-2-one is accompanied by formation of quinoxalyl ketone azine.

Full text of DOI:10.1023/A:1023415301274

Russian Journal of Organic Chemistry, Vol. 39, No. 1, 2003, pp. 131 140. Translated from Zhurnal Organicheskoi Khimii, Vol. 39, No. 1, 2003,
pp. 141 150.
Original Russian Text Copyright
2003 by Mamedov, Kalinin, Gubaidullin, Rizvanov, Chernova, Doroshkina, Litvinov, Levin.
Fused Nitrogen-Containing Heterocycles:
IV.* 3-Benzoyl-2-oxo-1,2-dihydroquinoxaline Hydrazones
and Flavazoles Derived Therefrom
V. A. Mamedov, A. A. Kalinin, A. T. Gubaidullin, I. Kh. Rizvanov, A. V. Chernova,
G. M. Doroshkina, I. A. Litvinov, and Ya. A. Levin
Arbuzov Institute of Organic and Physical Chemistry, Kazan Research Center, Russian Academy of Sciences,
ul. Arbuzova 8, Kazan, 420088 Tatarstan, Russia
e-mail: mamedov@iopc.kcn.ru
Received June 27, 2001
Abstract 3-Benzoyl-1,2-dihydroquinoxalin-2-one reacts with hydrazine and thiosemicarbazide to give the
corresponding hydrazone and thiosemicarbazone. The reaction with arylhydrazines yields 3-( -arylazoben-
zylidene)-1,2,3,4-tetrahydroquinoxalin-2-ones which are tautomeric to the respective arylhydrazones. On
heating in boiling acetic acid, the products of both types undergo intramolecular cyclocondensation with
formation of 3-phenylpyrazolo[3,4-b]quinoxalines (3-phenylflavazoles). 3-Benzoyl-1,2-dihydroquinoxalin-
2-one thiosemicarbazone gives rise to flavazole structure only in the presence of methyl 3-chloro-2-oxo-3-
phenylpropionate as a trap of thiocarbamoyl moiety. The cyclization of 3-( -hydrazonobenzyl)-1,2-dihydro-
quinoxalin-2-one is accompanied by formation of quinoxalyl ketone azine.
The -dicarbonyl fragment in 3-benzoyl-1,2-di-
hydroquinoxalin-2-one (I) contains both ketone and
lactam carbonyl groups; therefore, this compound
seems to be very promising from the viewpoint of
fusion of various heterocyclic systems to its pyrazine
ring. Ketone I has become accessible as a result of
our studies [2 4]. In the present work we examined
the possibility for preparation of hydrazones II
and their subsequent intramolecular cyclization to
3-phenylpyrazolo[3,4-b]quinoxalines III (phenyl-
flavazoles) [5].
semicarbazide afforded products whose elemental
compositions were similar to those expected for
hydrazones II (Scheme 1, Table 1). Unsubstituted
hydrazone IIa was obtained in high yield by reaction
in dioxane at room temperature. Arylhydrazones IIb
and IIc were formed in boiling dioxane, and the
reaction with thiosemicarbazide required heating in
boiling acetic acid. The synthesis of dinitrophenyl-
hydrazone IIe from less reactive and poorly soluble
2,4-dinitrophenylhydrazine was performed in a mix-
ture of acetic amd sulfuric acids.
Judging by the presence in the IR spectra of strong
The reactions of ketone I with hydrazine, phenyl-,
4-tolyl-, and 2,4-dinitrophenylhydrazines, and thio-
1
absorption bands in the region 1660 1675 cm
Scheme 1.
R = H (a), Ph (b), 4-MeC6H4 (c), 2,4-(O2N)2C6H3 (d), C(S)NH2 (e).
____________
*
For communication III, see [1].
1070-4280/03/3901-0131$25.00 2003 MAIK Nauka/Interperiodica

132
MAMEDOV et al.
Table 1. Yields, melting points, and elemental analyses of quinoxaline derivatives IIa IIe, IIIa IIIc, V, and VI
Found, %
H
Calculated, %
H
Comp. Yield, %
mp, C (solvent)
Formula
no.
(method)
C
N
C
N
IIa
IIb
IIc
IId
IIec
IIIa
80
99
80
93
89
80 (a)
28 (b)
78 (a)
74 (b)
62 (a)
95 (b)
74 (c)
35
152 154a
68.05
74.19
74.35
59.41
58.75
73.05
4.58
4.58
5.20
4.03
2.86
4.05
21.32
16.44
15.76
21.16
18.85
22.97
C15H12N4O
C21H16N4O
C22H18N4O
C21H14N6O5
C16H13N5OS
C15H10N4
68.17
74.10
74.56
59.42
58.61
73.16
4.66
4.74
5.12
4.05
3.28
4.09
21.20
16.46
15.81
21.66
19.53
22.75
266 268 (AcOH)b
234 236 (MeCN)
329 331 (i-PrOH)
266 269 (DMSO)
262 263 (AcOH)
IIIb
IIIc
235 237 (DMSO
MeCN, 2: 1)d
208 210 (DMSO
MeCN, 2: 1)
78.34
74.72
4.57
4.67
17.08
16.74
C21H14N4
C22H16N4
78.24
78.55
4.38
4.79
17.38
16.66
Ve
>360a
252 254 (AcOH)
C30H20N6O2
C26H17N5O2S
VIf
81
67.57
3.68
15.20
67.37
3.70
15.11
a
b
c
d
e
f
The product was washed with isopropyl alcohol.
Published data [6]: mp 248 250 C.
Found, %: S 9.67. Calculated, %: S 9.91.
Published data [7]: mp 233 234 C.
Mass spectrum, m/z: 496.1661 [M]+. Calculated: M 496.1647.
Found, %: S 6.42. Calculated, %: S 6.92.
(Table 2), compounds IIa IIe, as well as initial
ketone I [2 4], have lactam structure. As concerns
fine details of the structure of the hydrazone and
pyrazine fragments, some conclusions may be drawn
from analysis of the electron absorption and H NMR
spectra (Tables 2, 3).
Hydrazones derived from aromatic and heterocyclic
ketones [Ar2CO, Het2CO, HetC(O)Ar] and having at
least one hydrogen atom on the amino nitrogen atom
are capable of existing as the corresponding azo
tautomers [8]. Hydrazones like Het(Ar)CNNHR (II)
could give rise to a greater number of tautomers due
to proton transfer not only to the imino carbon atom
but also to the quinoxaline N4 atom which is
a member of the conjugated HN N C C N
pentad. Therefore, depending on the nature of the R
substituent, aggregate state, and solvent, compounds
II can exist as hydrazone (A), azoenamine (B), and
azo tautomer (C). For each of the above structure,
E/Z isomerism with respect to the exocyclic C N
and/or N N bonds is possible. Z,Z-Hydrazone and
E,E-azoenamine tautomers can be stabilized by intra-
molecular hydrogen bonds (just these structures are
shown for tautomers A and B).
1
Compounds IIa IIe were assigned structures like
A, B, and C without distinguishing stereoisomeric
forms and modes of intramolecular hydrogen bonding.
The structure of hydrazones derived from 3-acyl-1,2-
dihydroquinoxalin-2-ones (which were synthesized by
azo coupling of 3-methyl- and 3-R-CH2-substituted
1,2-dihydroquinoxalin-2-ones or, more seldom, by
reaction of 3-formyl-1,2-dihydroquinoxalin-2-ones
with arylhydrazines) was discussed in [9 22]. The
1H NMR spectra of IIa IIe contain no signal from
proton at sp3-hybridized carbon atom ( 6.0 6.5 ppm,
Table 2), which is typical of 3-( -X-benzyl)-1,2-di-
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FUSED NITROGEN-CONTAINING HETEROCYCLES: IV.
133
Table 2. IR and 1H NMR spectra of quinoxaline derivatives IIa IIe, IIIa IIIc, V, and VI
Comp.
no.
1
IR spectrum, , cm
1H NMR spectrum, , ppm (solvent)
IIa
IIb
1125, 1480, 1530, 1610, 1660, 2500 3100 br, 7.21 7.81 m (10H, 5-H, 6-H, 7-H, C6H5, NH2), 7.83 d (1H,
3205 br, 3270 br, 3380 br 8-H, J = 7.96 Hz), 12.45 br.s (1H, NH) (DMSO-d6)
1105, 1140, 1153, 1230, 1242, 1430, 1495, 6.78 6.81 m (1H, p-H in NPh), 7.16 7.65 m (12H, 5-H, 6-H,
1520, 1540, 1598, 1670, 2500 3100 br
7-H; CC6H5; o-H, m-H in NPh), 7.85 d (1H, 8-H, J =
7.28 Hz), 9.80 s (1H, 4-H), 12.48 br.s (1H, 1-H) (CD3CN)
IIc
IId
1103, 1230, 1255, 1525, 1623, 1675, 2350 2.25 s (3H, Me), 7.03 d (2H, o-H in MeC6H4, J = 8.10 Hz),
3100 br
7.09 d (2H, m-H in MeC6H4, J = 8.10 Hz), 7.26 7.69 m (8H,
5-H, 6-H, 7-H, C6H5), 7.90 d (1H, 8-H, J = 7.30 Hz), 9.28 s
(1H, 4-H), 10.41 br.s (1H, 1-H) (CD3CN)
1090, 1315, 1340, 1420, 1495, 1590, 1615, 7.45 7.50 m (5H, C6H5), 7.72 7.79 m (3H, 12H, 5-H, 6-H,
1660, 3105, 2400 3300 br
7-H), 8.00 d.d (1H, 8-H, J = 7.13, 1.29 Hz), 8.25 d (1H, 6-H
in C6H3, J = 9.55 Hz), 8.47 d.d (1H, 5-H in C6H3, J = 9.55,
8.60 Hz), 8.85 d (1H, 3-H in C6H3, J = 2.60 Hz), 12.28 s
(1H, 4-H), 12.90 br.s (1H, 1-H) (DMSO-d6)
IIe
1075, 1265, 1290, 1430, 1445, 1490, 1520, 7.75 7.91 m (DMSO-d6)
1605, 1630, 1665, 2000 3200 br, 3090,
3180, 3260, 3300, 3415
IIIa 980, 1132, 1210, 1300, 1345, 1460, 1505, 7.56 7.75 m (3H, m-H, p-H), 7.95 d.d.d. (1H, 7-H, J7,8 = 8.4,
1598, 2700 3300 br
J7,6 = 8.3, J7,5 = 2.2 Hz), 8.05 d.d.d. (1H, 6-H, J6,7 = 8.3,
J6,5 = 8.5, J6,8 = 1.6 Hz), 8.27 d.d.d. (1H, 8-H, J8,7 = 8.4,
J8,6 = 1.6, J8,5 = 1.0 Hz), 8.45 d.d.d. (1H, 5-H, J5,6 = 8.5,
J5,7 = 2.2, J5,8 = 1.0 Hz), 8.70 8.73 m (2H, o-H), 14.28 br.s
(1H, 1-H) (DMSO-d6)
IIIb 1130, 1360, 1420, 1490, 1560, 1590
7.85 8.90 m (DMSO-d6)
IIIc 992, 1120, 1135, 1207, 1260, 1360, 1430, 2.44 s (3H, Me), 7.41 d (2H, m-H in C6H4, J = 8.34 Hz), 7.45
1495, 1515, 1565, 1615
7.62 m (3H, m-H, p-H in C6H5), 7.82 d.d.d (1H, 6-H or 7-H,
J = 7.71, 5.95, 1.39 Hz), 7.91 d.d.d. (1H, 7-H or 6-H, J =
7.63, 5.92, 1.36 Hz), 8.24 d.d (1H, 5-H or 8-H, J = 8.34,
1.12 Hz), 8.38 d.d (1H, 8-H or 5-H, J = 8.34, 1.14 Hz),
8.42 d (2H, o-H in C6H4, J = 8.34 Hz), 7.75 8.81 m (2H,
o-H in Ph) (CD3COOD)
V
1288, 1420, 1572, 1600, 1654, 1690
7.73 8.07 m (DMSO-d6)
VI
1080, 1135, 1160, 1175, 1200, 1260, 1270, 3.73 s (3H, Me), 7.45 7.70 m (8H, 5 -C6H5, m-H and p-H in
1330, 1355, 1410, 1470, 1500, 1520, 1535,
1585, 1722
3-C6H5), 7.89 d.d (1H, 6-H or 7-H, J = 7.81, 7.39 Hz),
7.98 d.d (1H, 7-H or 6-H, J = 7.81, 7.39 Hz), 8.31 br.d (1H,
5-H or 8-H, J = 8.48 Hz), 8.41 br.d (1H, 8-H or 5-H, J =
8.50 Hz), 7.75 8.82 m (2H, o-H in 3-C6H5) (CD3COOD)
hydroquinoxalin-2-ones (X = Cl, SCN, N3, NHPh)
[1, 2, 23]; therefore, azobenzyl structure C can be
ruled out. Compounds IIa IIe can be divided into two
groups according to their color and electron absorp-
tion spectra (Table 3). The first group consists of
hydrazone IIa and thiosemicarbazone IIe. They show
in the electron absorption spectra a strong band in the
long-wave UV region or short-wave visible region.
The visible region of the spectrum contains neither
absorption maxima nor shoulders. The second group
includes red orange products IIb IId obtained from
arylhydrazines. Their electron absorption spectra in
dioxane are characterized by the presence of strong
bands in the region 440 460 nm (log 4).
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134
MAMEDOV et al.
Table 3. Electron absorption spectra of compounds IIa IIe, max, nm (log )
Comp.
Dioxane
no.
Ethanol
IIa
IIb
227 (4.41), 276.5 (4.11), 341 sh (3.72), 355 (3.76), 225 (4.42), 248 sh (4.09), 257 (4.07), 275 (4.05), 347 sh
369 sh (3.69) (3.94), 358 (3.98), 369 sh (3.94)
232 (4.55), 291 (4.21), 296 (4.22), 331 (4.29), 440 232 (4.67), 296 (4.35), 336 (4.45), 425 (3.76), 454 sh
(3.69), 461 sh (3.68)
(3.69)
IIc
IId
233 (4.55), 296 (4.26), 336 (4.29), 459 (3.73)
226 (4.64), 286 (4.23), 365 sh (4.38), 388 (4.34),
440 sh (4.17)
231 (4.57), 296 (4.29), 339 (4.36), 436 (3.74), 488 sh
(3.59)
IIea 315 (4.41), 361 sh (3.98)
a
In DMSO.
Like hydrazones of the first group, light yellow
of 4-H was observed for the 4-nitrophenyl derivative,
11.9 ppm [21]. The shape of the 4-H signal in the
1H NMR spectra of IIb IId suggests either stability
of tautomer B under the conditions of spectral
measurements or, by contrast, fast interconversion
of tautomers (NH protons of different tautomers give
a common signal). Distinctive features of tautomers
A and B require further studying; nevertheless, all
the above stated suggests structure B for compounds
IIb IId.
color is characteristic of 3-formyl-2-oxo-1,2-dihydro-
quinoxaline hydrazones obtained from N-methyl-N-
phenylhydrazine and N-acetyl-N-phenylhydrazine [9].
These compounds have fixed structure A, while
tautomers like B and C, having a chromophoric azo
group, cannot be formed. Therefore, unsubstituted
hydrazone IIa and thiosemicarbazone IIe were as-
signed structure A. This assignment is supported by
the presence in the IR spectrum of IIa of three
medium-intensity bands which can be attributed to
1
Judging by the presence in the H and 13C NMR
spectra of signals typical of both hydrazone and
enamine structures, most 3-acyl-2-oxo-1,2-dihydro-
quinoxaline arylhydrazones studied so far exist in
solution as equilibrium mixtures of hydrazone and
azoenamine tautomers A and B [12, 14 22]. By con-
trast, the 1H NMR spectra of compounds IIa IId
(Table 2) indicate the presence of only one tautomer.
The spectra of IIb IId lack HNAr signal from aryl-
hydrazone moiety, which was observed in a very weak
field ( 14.4 15.2 ppm) for tautomeric mixtures of
arylhydrazones derived from 2-oxo-3-formyl-1,2-di-
hydroquinoxaline [21].
stretching vibrations of the NH2 group: 3380 ( as),
1
3270 ( as), and 3205 cm ( ).
s
Red orange derivatives IIb IIe characterized by
strong absorption in the visible region of the electron
spectra are likely to have azoenamine structure B or,
at least, azoenamine tautomer should be present in
the isomer mixture (in Experimental, compounds IIb
IIe are named as tautomers B). The IR spectra of IIb
and IIc contain no other NH bands than that typical
of lactam moiety (a very broad absorption band with
1
a complex shape in the region 2400 3100 cm ).
1
Finally, in the downfield region of the H NMR
Acid solutions of arylhydrazones IIb IId having
structure B, as well as of other structurally related
compounds [10, 18 20], are violet due to charge de-
localization in the protonated species which may be
represented by canonical structures IV (Scheme 2).
Like hydrazones derived from other 3-acyl-2-oxo-
1,2-dihydroquinoxalines [6, 9, 22, 24 27], heating of
compounds IIa IIc in boiling acetic acid leads to
intramolecular ring closure with loss of water mole-
cule and formation of pyrazolo[3,4-b]quinoxalines
(flavazoles) IIIa IIIc (Scheme 1, Table 1). Dinitro-
rophenylhydrazone IId did not undergo analogous
transformation even in polyphosphoric acid. The intra-
molecular cyclization of hydrazone IIa was accom-
spectra of IIb IId, unlike hydrazone IIa, we observed
a broadened singlet at
10.4 12.9 ppm from the
lactam NH group and a narrow one-proton singlet at
9.3 12.3 ppm. Presumably, the latter belongs to the
4-H proton in azoenamine structure B. An analogous
signal was present in the spectra of azoenamine aryl-
hydrazone tautomers [21]. The chemical shift of 4-H
in IIb IId is considerably influenced by the substit-
uent in the benzene ring at the azo group. Strong elec-
tron-acceptor substituents (e.g., nitro groups in IId)
induce a downfield shift of that signal relative to the
corresponding signal in the spectra of IIb and IIc
(
9.3 9.8 ppm). In the series of 3-formyl-2-oxo-
quinoxaline hydrazones, the maximal chemical shift
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FUSED NITROGEN-CONTAINING HETEROCYCLES: IV.
135
Scheme 2.
panied by formation of the corresponding ketone azine
V (Scheme 3). Compounds IIIa IIIc can be obtained
directly from ketone I and excess hydrazine in boiling
acetic acid or by heating ketone I with excess aryl-
hydrazine hydrochloride in boiling dioxane. Here, the
presence of excess hydrazine prevents formation of
ketone azine V.
corresponding to formation of hydrazones II. We
failed to isolate thiazolyl analog of II in the above
reaction. The structure of flavazoles IIIa IIIc and VI
was confirmed by elemental analyses and spectral data
(Tables 1, 2). The presence of a labile hydrogen atom
in molecule IIIa gives rise to five possible tautomeric
structures D H where this proton is localized on N1,
N2, N4, N9, or C3.
Scheme 3.
Our attempts to synthesize flavazole IIIe by
dehydration of thiosemicarbazone IIe, as well as by
one-step procedure from ketone I, were unsuccessful.
Presumably, the reason is the presence of a thiocarb-
amoyl moiety which can be involved in various side
pocesses. Nevertheless, thiosemicarbazone IIe was
converted into the corresponding flavazole structure
by heating in dioxane in the presence of methyl
3-chloro-2-oxo-3-phenylpropionate as a trap for thio-
carbamoyl functionality. This compound is known to
readily react with thioamides, affording thiazole
derivatives [28, 29]. As a result, we obtained 1-thia-
zolyl-substituted pyrazoloquinoxaline VI in high yield
(Scheme 4). The cyclization occurred especially
readily in boiling dioxane, i.e., under the conditions
1
The H NMR spectrum of a solution of IIIa in
DMSO-d6 (Table 2) lacks CH proton signal but con-
tains a downfield signal at 14.28 ppm (NH). These
data allow us to rule out tautomer H. The multi-
plicities of signals from protons of the quinoxaline
fragment originate from couplings between only four
nonequivalent protons in the aromatic moiety without
participation of the NH proton. Therefore, structures
E and G with NH proton localized in the pyrazine
fragment are less probable than D and F where that
proton appears in the pyrazole fragment. In order to
refine the chemical shifts and coupling constants,
Scheme 4.
1
the H NMR spectrum of IIIa was sumulated using
PANIC program (correlation coefficient R = 0.997);
the resulting values are given in Table 2. Analogous
conclusions may be drawn for a solution in CDCl3.
The structure of compound IIIa in crystal was
established by X-ray analysis. Crystals of IIIa are
rhombic with one molecule in the symmetrically
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 1 2003

136
MAMEDOV et al.
cular hydrogen bonds with identical parameters: they
are formed by the H1 hydrogen atom and N9 atom of
the pyrazole fragment with the corresponding nitrogen
and hydrogen atoms of two neighboring molecules
which are related to the first molecule through
a second-order screw axis (Fig. 2). The following
hydrogen bond parameters were obtained for the
systems donor(hydrohen) acceptor (D H A) using
the standard criterion for H-bonding, d(D A) <
R(D) + R(A) + 0.50E, d(H A) < R(H) + R(A)
0.12E, DHA > 100.00 (here, R is van der Waals
radius of the corresponding atom).
DHA triad
D H,
C11H11N4 C15H15N2 N1H1N9
0.97(4)
2.45(3)
1.04(4)
2.36(4)
0.86(3)
2.05(3)
2.906(4)
169(3)
H
D
A,
A,
,
3.157(5) 2.842(6)
130(2) 107(2)
DHA, deg
Fig. 1. Structure of the molecule of 3-phenylpyrazolo-
[3,4-b]quinoxaline (IIIa).
Molecules of IIIa in crystal are linked by hydrogen
bonds to form infinite chains along the crystallogra-
phic x axis which coincides with the second-order
screw axis. The mode of crystal packing is strongly
affected by , interactions between electron systems
of the pyrazoloquinoxaline fragments. The resulting
supramolecular structure can be described as follows:
independent part. The structure of molecule IIIa is
shown in Fig. 1. The position of the labile hydrogen
atom (on N1) was unambiguously determined from the
difference synthesis of electron density. The pyrazolo-
quinoxaline ring system is planar within experimental
error [0.07 (1) ], and the phenyl substituent lies
almost in the same plane [the corresponding dihedral
angle is 6.2 (2) ]. Two C H N intramolecular
hydrogen bonds are formed between H15 and N2 and
between H11 and N4. Also, there are two intermole-
an almost planar molecule of IIa participates in
,
interactions with two neighboring molecules which
are related to the former through +1 and 1 translation
along the crystallographic x axis, i.e., an infinite stack
of molecules along that axis is obtained. Here, the
ring planes are not orthogonal to the x axis, and no
hydrogen bonding exists between molecules in the
stack. The stacks of molecules constrained through
second-order screw axis are linked in pairs by hydro-
gen bonds (Fig. 3). The tightest crystal packing is
attained via parallel laying of the H-bonded stack
pairs along the 0x crystallographic axis. This leads
to anisotropic properties of the crystal.
EXPERIMENTAL
The melting points were determined on a Boetius
device. The IR spectra were measured on a UR-20
spectrometer from samples dispersed in mineral oil.
1
The H NMR spectra of compounds IIe, IIIa IIIc,
and V were recorded on a Bruker WM-250 instrument
at 250.1 MHz, and of the other products, on a Bruker
MSL-400 spectrometer at 400.1 MHz. The chemical
shifts were measured relative to the residual proton
signals of the deuterated solvent. The electron absorp-
tion spectra were measured on a Specord UV-Vis
spectrophotometer. The mass spectrum of V (electron
Fig. 2. Intra- and intermolecular hydrogen bonds (dashed
lines) in the crystalline structure of 3-phenylpyrazolo-
[3,4-b]quinoxaline (IIIa).
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FUSED NITROGEN-CONTAINING HETEROCYCLES: IV.
137
Table 4. Bond lengths d ( ), bond angles
[3,4-b]quinoxaline (IIIa)
(deg), and torsion angles (deg) in the molecule of 3-phenylpyrazolo-
Bond
d,
Bond
d,
Bond
d,
Bond
d,
N1 N2
N1 C9a
N1 H1
N2 C3
N4 C3a
N4 C4a
N9 C8a
N9 C9a
1.387(5)
1.341(6)
0.87(3)
1.326(5)
1.322(5)
1.381(5)
1.361(5)
1.315(6)
C3a C3
C3a C9a
C3 C10
C4a C5
C4a C8a
C5 C6
1.436(6)
1.420(5)
1.456(6)
1.400(6)
1.418(5)
1.351(6)
1.03(3)
C6 H6
0.93(3)
1.350(6)
1.09(4)
1.439(6)
1.07(3)
1.372(6)
1.402(7)
1.384(7)
C11 H11
C12 C13
C12 H12
C13 C14
C13 H13
C14 C15
C14 H14
C15 H15
0.97(3)
1.387(8)
1.20(5)
1.389(8)
0.98(5)
1.376(7)
1.07(5)
1.05(3)
C7 C8
C7 H7
C8a C8
C8 H8
C10 C11
C10 C15
C11 C12
C5 H5
C6 C7
1.405(6)
Angle
, deg
Angle
, deg
Angle
, deg
Angle
, deg
N2N1C9a
N2N1H1
C9aN1H1
N1N2C3
C3aN4C4a
C8aN9C9a
N4C3aC3
N4C3aC9a
C3C3aC9a
N2C3C3a
C7C6H6
111.8(3)
116.0(3)
132.0(3)
107.6(3)
114.4(3)
112.6(3)
131.2(3)
122.4(4)
106.4(3)
108.4(3)
123.0(2)
N2C3C10
C3aC3C10
N4C4aC5
N4C4aC8a
C5C4aC8a
C4aC5C6
C4aC5H5
C6C5H5
120.8(4)
130.8(3)
119.5(3)
121.3(4)
119.2(4)
121.0(4)
119.0(2)
120.0(2)
120.6(4)
116.0(2)
C6C7H7
123.0(2)
116.0(2)
123.8(4)
118.0(3)
118.2(4)
120.1(4)
123.0(2)
117.0(2)
128.8(4)
105.7(4)
N9C9aC3a
C3C10C11
C3C10C15
C11C10C15
C10C11C12
C11C12C13
C12C13C14
C10C15C14
C13C14C15
C6C7C8
125.5(4)
120.5(4)
120.2(4)
119.2(4)
121.4(5)
119.4(5)
119.6(5)
119.6(4)
120.7(5)
120.7(4)
C8C7H7
N9C8aC4a
N9C8aC8
C4aC8aC8
C7C8C8a
C7C8H8
C8aC8H8
N1C9aN9
N1C9aC3a
C5C6C7
C5C6H6
Angle
, deg
Angle
, deg
Angle
, deg
Angle
, deg
C9aN1N2C3
H1N1N2C3
0(4)
178.0(2)
179.8(4)
0.7(5)
2.0(3)
177.0(3)
0.6(4)
178.6(3)
179.5(4)
1.5(5)
179.5(4)
1.2(6)
1.5(6)
179.4(4)
177.4(4)
C8aN9C9aC3a
N4C3aC3N2
N4C3aC3C10
C9aC3aC3N2
C9aC3aC3C10
N4C3aC9aN1
N4C3aC9aN9
C3C3aC9aN1
C3C3aC9aN9
N2C3C10C11
N2C3C10C15
C3aC3C10C11
C3aC3C10C15
N4C4aC5C6
N4C4aC5H5
1.9(6)
177.2(4)
3.7(8)
C4aC5C6H6
H5C5C6C7
H5C5C6H6
C5C6C7C8
C5C6C7H7
H6C6C7C8
H6C6C7H7
C6C7C8C8a
C6C7C8H8
H7C7C8C8a
H7C7C8H8
N9C8aC8C7
N9C8aC8H8
C4aC8aC8C7
C4aC8aC8H8
179.0(2)
179.0(2)
1.0(3)
C3C10C11C12
C15C10C11C12
C3C10C15C14
C11C10C15C14
C10C11C12C13
C11C12C13C14
C12C13C14C15
C13C14C15C10
C5C4aC8aN9
C5C4aC8aC8
C4aC5C6C7
178.5(5)
0.8(7)
177.0(4)
0.6(6)
N2N1C9aN9
N2N1C9aC3a
H1N1C9aN9
H1N1C9aC3a
N1N2C3C3a
N1N2C3C10
C4aN4C3aC3
C4aN4C3aC9a
C3aN4C4aC5
C3aN4C4aC8a
C9aN9C8aC4a
C9aN9C8aC8
C8aN9C9aN1
1.0(5)
0.7(7)
178.1(4)
177.4(4)
2.1(7)
177.0(2)
179.0(2)
3.0(3)
1.8(8)
1.3(8)
0.1(8)
1.1(7)
1.1(5)
1.8(6)
179.5(4)
173.9(4)
3.8(6)
176.0(2)
178.0(2)
7.0(3)
179.3(4)
4.0(2)
179.6(4)
2.6(6)
0.6(7)
1.6(6)
179.0(2)
1.3(6)
179.1(4)
5.2(7)
C8aC4aC5C6
C8aC4aC5H5
N4C4aC8aN9
N4C4aC8aC8
177.2(5)
179.9(4)
0(2)
2.7(6)
178.0(2)
impact, 70 eV) was obtained on an MKh-1310 instru-
ment at a resolution R of 15000 (electron collector
current 60 A; ion source temperature 120 C; direct
sample admission into the ion source using an SVP-5
direct inlet probe).
The X-ray diffraction data for a single crystal of
IIIa were obtained on an Enraf Nonius CAD-4 four-
circle automatic diffractometer. Rhombic crystals,
C15N4H11; unit cell parameters (20 C): a = 4.8275(6),
3
b = 19.294(4), c = 12.954(3) ; V = 1206.5(4)
;
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 1 2003

138
MAMEDOV et al.
properties and the absence of depression of the
melting point of a mixed sample.
3-( -Hydrazonobenzyl)-1,2-dihydroquinoxalin-
2-one (IIa). A suspension of 0.50 g (2.0 mmol) of
ketone I in a mixture of 1 ml of 60% hydrazine
hydrate and 6 ml of dioxane was stirred for 24 h at
room temperature. The initial compound dissolved,
and crystals of the product separated. The precipitate
was filtered off and washed with isopropyl alcohol.
3-( -Phenylazobenzylidene)-1,2,3,4-tetrahydro-
quinoxalin-2-one (IIb). A solution of 0.30 g
(1.2 mmol) of ketone I and 0.5 ml of phenylhydrazine
in 15 ml of dioxane was heated for 2 h under reflux.
The mixture was cooled, and the precipitate was
filtered off and washed with isopropyl alcohol.
3-[ -(4-Tolylazo)benzylidene]-1,2,3,4-tetrahydro-
quinoxalin-2-one (IIc). A suspension of 0.50 g
(2.0 mmol) of ketone I, 0.63 g (4.0 mmol) of 4-tolyl-
hydrazine hydrochloride, and 0.20 g (3.6 mmol) of
potassium hydroxide in 20 ml of dioxane was heated
for 1 h under reflux. The mixture was filtered, the
filtrate was poured into water acidified with acetic
acid, and the precipitate was filtered off and washed
with water.
3-[ -(2,4-Dinitrophenylazo)benzylidene]-1,2,3,4-
tetrahydroqunoxalin-2-one (IId). 2,4-Dinitrophenyl-
hydrazine, 0.30 g (1.5 mmol), was dissolved in 6 ml
of concentrated sulfuric acid, 6 ml of water was care-
fully added with stirring, and a boiling solution of
0.30 g (1.2 mmol) of ketone I in 10 ml of acetic
acid was added to the warm mixture. Red crystals
separated, and the mixture was left overnight. It was
then diluted with 12 ml of water, and, after 1 h, the
crystals were filtered off and washed with water and
isopropyl alcohol.
3-( -Thiosemicarbazonobenzyl)-1,2-dihydro-
quinoxalin-2-one (IIe). A solution of 0.40 g
(1.60 mmol) of ketone I and 0.16 g (1.76 mmol) of
thiosemicarbazide in 7 ml of acetic acid was heated
for 3 h under reflux. The mixture was cooled, and
the precipitate was filtered off and washed with iso-
propyl alcohol.
3-Phenylpyrazolo[3,4-b]quinoxaline (IIIa) and
N,N -Bis[phenyl(2-oxo-1,2-dihydroquinoxalin-3-yl)-
methylene]hydrazine (V). a. A solution of 0.50 g
(2 mmol) of ketone I and 1 ml of 60% hydrazine
hydrate in 7 ml of acetic acid was heated for 2 h under
reflux. The mixture was cooled, and the crystals of
pyrazoloquinoxaline IIIa were filtered off and washed
with isopropyl alcohol and water.
Fig. 3. Hydrogen bonded stacks of molecules in the crys-
talline structure of 3-phenylpyrazolo[3,4-b]quinoxaline
(IIIa). Only the H1 hydrogen atom is shown, which is
involved in intermolecular contacts (dashed lines). A view
approximately along the 0x crystallographic axis.
Z = 4;
= 1.36 g/cm3; space group P212121. The
calc
unit cell parameters and intensities of 1643 reflections
(749 of which with I 3 ) were measured at 20 C;
MoK , graphite monochromator, /2 scanning,
26.3 . No reduction in intensity of three control
reflections was observed during the measurements.
The structure was solved by the direct method using
SIR program [30] and was refined first in isotropic
and then in anisotropic approximation. Hydrogen
atoms were visualized from the difference series of
electron density; in the final cycles of the least-
squares procedure, their positions were refined in
isotropic approximation. The final divergence factors
were R = 0.0419 and Rw = 0.042 (from 882 reflec-
tions with F2 3 ). All calculations were performed
with the aid of MolEN software [31] on an Alpha-
Station 200 computer. Some geometric parameters of
molecule IIIa are listed in Table 4. The molecular
structure and crystal packing shown in Figs. 1 3 were
plotted, and the parameters of intra- and intermole-
cular interactions were calculated, using PLATON
software [32].
When the same compound was synthesized by
different methods, the identity of the products was
established on the basis of their physical and spectral
b. A solution of 0.20 g (0.76 mmol) of hydrazone
IIa in 3 ml of acetic acid was heated for 1.5 h under
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 1 2003

FUSED NITROGEN-CONTAINING HETEROCYCLES: IV.
reflux. The mixture was cooled, and the precipitate REFERENCES
139
(a mixture of compounds IIIa and V) was filtered
off. The product mixture was heated for 2 min in
15 ml of boiling acetic acid, and the precipitate of
ketone azine V was filtered off from the hot mixture
and washed with isopropyl alcohol. The filtrate was
cooled, and the crystals of pyrazoloquinoxaline IIIa
were filtered off and washed with isopropyl alcohol
and water.
1,3-Diphenylpyrazolo[3,4-b]quinoxaline (IIIb).
a. A solution of 0.20 g (0.80 mmol) of ketone I and
0.7 ml of phenylhydrazine in 15 ml of acetic acid was
heated for 9 h under reflux and was then left over-
night. The precipitate was filtered off and washed
with isopropyl alcohol.
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