Quinoxalines X [1]. A new and convenient synthesis of 1H-pyrazolo[3,4-b]quinoxalines (flavazoles)

Article abstract of DOI:10.1002/jhet.5570380404

Quinoxaline-2-aldoximes and -ketoximes (6) react with hydrazine, alkylhydrazines or arylhydrazines under acidic conditions to afford 1H-pyrazolo[3,4-b]quinoxalines (flavazoles) (1). Since the oximes (6) are easily available from phenylenediamine, the herein described methodology provides a convenient two step entry to various functionalized flavazoles. Furthermore, acylation and alkylation of the 1-unsubstituted 1H-pyrazolo[3,4-b]quinoxalines 7 proceeds smoothly and in good yield to afford 31 different flavazoles 11 and 12.

Full text of DOI:10.1002/jhet.5570380404

Jul-Aug 2001
Quinoxalines X [1]. A New and Convenient Synthesis
of 1H-Pyrazolo[3,4-b]quinoxalines (Flavazoles)
Gerhard Sarodnick and Torsten Linker*
829
Department of Chemistry, University of Potsdam, Karl-Liebknecht-Str. 24-25, D-14476 Golm, Germany
Received February 20, 2001
th
Dedicated to Professor Gerhard Kempter on the occasion of his 70 birthday
Quinoxaline-2-aldoximes and -ketoximes (6) react with hydrazine, alkylhydrazines or arylhydrazines
under acidic conditions to afford 1H-pyrazolo[3,4-b]quinoxalines (flavazoles) (1). Since the oximes (6) are
easily available from phenylenediamine, the herein described methodology provides a convenient two step
entry to various functionalized flavazoles. Furthermore, acylation and alkylation of the 1-unsubstituted
1H-pyrazolo[3,4-b]quinoxalines 7 proceeds smoothly and in good yield to afford 31 different flavazoles 11
and 12.
J. Heterocyclic Chem., 38, 829 (2001).
1H-Pyrazolo[3,4-b]quinoxalines (flavazoles) (1) are a
In our initial experiments, we focused on the simple
reaction of the oximes 6 with hydrazine hydrate under
acidic conditions. After optimization, cheap hydrochloric
acid was found to give the best results. Indeed, the desired
flavazoles 7 were isolated in only one step in high yield
(Scheme 2). In the first step of the reaction, hydrazones 8
were obviously formed in situ by the elimination of
group of heterocyclic compounds, which are of great
biological interest. In early studies they were used for the
characterization of carbohydrates [2]. More recently, flava-
zoles were found to exhibit a high antibacterial activity [3],
significant diuretic and antiinflammatory properties [4],
antifungal activity [5], as well as cytotoxic effects [6].
Besides a few examples of pyrazine cyclizations [7], the
most common synthesis of the flavazole system start from
quinoxaline hydrazones 2 by dehydrogenation [8],
dehydration [9], or dehydrochlorination [3,6,10].
However, expensive reagents like azobenzene were used
for the dehydrogenations. Furthermore, the requisite
hydrazones 2 had to be synthesized from carbonyl
compounds 3, which are oxidation labile and were only
available in small amounts [11].
To overcome this problem, we developed a convenient
one-pot synthesis of 2-acetylquinoxaline (3b) starting
from 1,2-phenylenediamine (4) and 2,3-butanedione
monoxime (5) via the oxime 6b on a large scale
(Scheme 1) [12]. Since oximes can be directly transformed
into hydrazones, we became interested in a new synthesis
of flavazoles in only a few steps starting from
1,2-phenylenediamine (4).
hydroxylamine. Acid catalyzed protonation of one ring
nitrogen induced directly the cyclization to the dihydro-
flavazoles 9, which were readily oxidized to the aromatic
system. This mechanistic proposal is in accordance with
literature known reactions of flavazole derivatives derived
from sugars [13]. Furthermore, it seems to provide an
explanation, why a similar acid catalyzed cyclization of
quinoline hydrazones fails [14], since there is not the
second ring nitrogen. Finally, the advantage of our strategy
described herein is not only the direct one-step synthesis of
flavazoles 7, but also the liberation of hydroxylamine,
acting as the oxidant in the last step. Thus, neither expen-
sive co-oxidants like azobenzene nor an excess of
hydrazine should be necessary for the reaction sequence.
To prove this hypothesis further and to evaluate the
scope and limitations of this new flavazole synthesis, we
investigated the one-pot reaction of the oximes 6 with a

830
G. Sarodnick and T. Linker
Vol. 38
the direct synthesis of flavazoles from oximes does not
only reduce the number of steps, but also no external
oxidant is necessary. This new strategy allowed the
synthesis of 15 different flavazoles 11 and 12 in moderate
to good yields (Table 1), and some of them showed
promising antifungal and antibacterial activity [3,15].
2
Interestingly, benzohydrazides 10 (R = COAr) did not
react with oximes 6 to the desired products under acidic
conditions, even after prolonged reaction times. To
investigate the reason for this behavior, we synthesized the
acylhydrazones 2i-k independently and treated these
compounds with strong acids. However, even under such
drastic conditions no cyclization occurred (Scheme 4).
Obviously, the acylated nitrogen atom is not nucleophilic
enough to attack the protonated quinoxaline ring. To
overcome this problem, the acylhydrazones 2 were cylized
in the presence of p-chloranil. This reagent induces radical
reactions by H-atom abstraction. Indeed, the so formed aza
radicals attack the quinoxaline ring intramoleculary to
afford the desired benzoyl flavazoles 12i-k after oxidation
to the aromatic system. However, due to side reactions
only moderate yields were achieved (Scheme 4).
broad variety of alkyl and aryl substituted hydrazines 10
(Scheme 3). Indeed, only 1.1 equivalent of hydrazine was
required for the complete conversion of the oximes 6,
indicating that hydrazine does not act as the oxidant. Thus,
To obtain higher yields of benzoyl flavazoles 12i-k and to
introduce various other substituents at N-1 of the flavazole
system, we became finally interested in the acylation and
alkylation of the unsubstituted flavazole 7b. Thus, a broad
variety of 11 additional flavazoles 12l-v were synthesized in
moderate to good yields (Scheme 5, Table 2).
In conclusion, we developed a new and convenient
synthesis of various flavazoles in only few steps starting
from phenylenediamine. The key step is the one-pot
transformation of oximes into the corresponding
flavazoles. The advantage of this strategy consists in the
elimination of hydroxylamine, which acts as the oxidant
for the final aromatization. Furthermore, acylation and
alkylation of the unsubstituted nitrogen offered an entry to
functionalized derivatives. Since many of such compounds
exhibit promising biological activities, the methodology
described herein would be applicable for the synthesis of
other flavazoles.

Jul-Aug 2001
Quinoxalines X. A New and Convenient Synthesis
831
+
7a, mp 280-282 °C; ms: m/z 170 (M ); ir: 3120, 3085, 3045,
2905, 2834, 1615, 1590, 1560, 1510, 1470, 1415, 1340, 1215,
1
1175, 1120, 1050, 920, 850, 755, 600, 550, 420; H nmr
(deuteriodimethyl sulfoxide): δ 13.13 (br, 1H, NH), 8.77
13
(s, 1H, 3-H), 8.27-7.82 (m, 4H, aromatic); C nmr (deuterio-
dimethyl sulfoxide): δ 143.2, 141.1, 140.7, 136.5, 134.5,
130.9, 130.0, 128.5, 128.0.
Anal. Calcd. for C H N : C, 63.52; H, 3.55; N, 32.92. Found:
9
6 4
C, 63.80; H, 3.61; N, 33.26.
3-Methyl-1H-pyrazolo[3,4-b]quinoxaline (7b).
Aqueous 20% hydrazine hydrate 7.5 ml (30 mmoles) and 5 ml
of 37% hydrochloric acid were added to a hot solution of 1.87 g
(10 mmoles) of oxime 6b in 75 ml of ethanol. The mixture was
heated at reflux for 4 hours, concentrated in vacuo and
neutralized with a 5% aqueous solution of sodium carbonate. The
solid was collected by filtration, washed with water and was
recrystallized from dioxane to yield 1.58 g (86%) of 7b, mp
+
224-226 °C; ms: m/z 184 (M ); ir: 3114, 3024, 2864, 2798, 1624,
1594, 1562, 1506, 1480, 1436, 1382, 1344, 1300, 1244, 1212,
1
1138, 1092, 980, 916, 814, 750, 650, 610, 590, 420; H nmr
(deuteriodimethyl sulfoxide): δ 13.64 (s, 1H, NH), 8.26-7.79
13
(m, 4H, aromatic), 2.73 (s, 3H, 3-CH ); C nmr (deuterio-
3
EXPERIMENTAL
dimethyl sulfoxide): δ 143.8, 142.3, 141.0, 139.9, 135.7, 130.5,
129.1, 128.2, 127.3, 11.51.
All melting points were determined on a Boetius micro
hotstage microscope (Fa. Analytik Dresden). The ir spectra
(potassium bromide) were recorded with a Perkin Elmer FTIR
Anal. Calcd. for C H N : C, 65.21; H, 4.38; N, 30.42. Found:
C, 65.45; H, 4.67; N, 30.19.
10
8 4
General Procedure for the Reaction of Oximes 6a and 6b with
Alkylhydrazines 10a and 10b.
-1
1600 spectrometer (cm ). The mass spectra (ms) were obtained
on a Finnigan-MAT SSQ 710 (70 eV). Elemental analyses were
performed on the autanalyser CHNS-932 (Fa. Leco instruments
GmbH); satisfactory microanalyses were obtained for all new
A solution of the appropriate alkylhydrazine 10a or 10b
(15 mmoles) in hot ethanol was added to a solution of 1.73 g
(10 mmoles) of oxime 6a or 1.83 g (10 mmoles) of oxime 6b in
100 ml of hot ethanol. After the addition of 5 ml of 37%
hydrochloric acid the mixture was heated at reflux for 5 hours.
The solution was concentrated in vacuo to 30 ml and was
neutralized with a 5% aqueous solution of sodium carbonate. The
mixture was kept in a refrigerator overnight and the precipitate
was collected by filtration, washed with water and recrystallized.
1
13
substances (C, H, N +/-0,3%). The H and C nmr spectra were
determined for solution in deuteriochloroform or deuterio-
dimethyl sulfoxide on a Bruker ARX 300 NMR spectrometer at
300.13 MHz and 75.47 MHz, respectively; the chemical shifts
are given in the δ scale (ppm) downfield from tetramethyl silane
(TMS) as internal standard.
1H-Pyrazolo[3,4-b]quinoxaline (7a).
1-Methyl-1H-pyrazolo[3,4-b]quinoxaline (11a).
Aqueous 20% hydrazine hydrate 7.5 ml (30 mmoles) and
5 ml of 37% hydrochloric acid were added to a hot solution of
1.73 g (10 mmoles) of oxime 6a in 75 ml of ethanol. The
mixture was heated at reflux for 4 hours, concentrated in vacuo
and neutralized with a 5% aqueous solution of sodium
carbonate. The solid was collected by filtration, washed with
water and recrystallized from toluene to yield 1.40 g (82%) of
This compound was obtained from 6a and methylhydrazine
sulphate (10a) in 72% yield as colorless needles (ethanol), mp
+
123.5-124.5 °C; ms: m/z 184 (M ); ir: 3095, 3060, 2920, 1615,
1575, 1485, 1435, 1405, 1355, 1330, 1200, 1150, 1095, 920, 905,
1
845, 810, 755, 740, 730, 650, 600; H nmr (deuteriochloroform):
δ 8.42 (s, 1H, 3-H), 8.18-7.64 (m, 4H, aromatic), 4.20 (s, 3H,

832
G. Sarodnick and T. Linker
Vol. 38
13
3
1-CH ); C nmr (deuteriochloroform): δ 141.9, 141.3, 140.9,
δ 8.47 (s, 1H, C -H), 8.30-7.98 (m, 4H, aromatic/quinoxaline),
3
13
136.5, 132.9, 130.5, 130.0, 128.4, 127.5, 34.1.
7.67-7.14 (m, 5H, aromatic/ phenyl); C nmr (deuterio-
Anal. Calcd. for C H N : C, 65.20; H, 4.38; N, 30.41. Found:
C, 65.40; H, 4.42; N, 30.34.
chloroform): δ 141.7, 141.4, 141.1, 139.2, 137.8, 135.0, 130.9,
130.0, 129.1 (2), 129.0, 128.2, 125.8, 119.8 (2).
10
8 4
Anal. Calcd. for C
Found: C, 73.27; H, 4.13; N, 22.98.
H N : C, 73.16; H, 4.09; N, 22.75.
15 10 4
1-tert-Butyl-1H-pyrazolo[3,4-b]quinoxaline (11b).
This compound was obtained from 6a and tert-butylhydrazine
hydrochloride (10b) in 77% yield as colorless needles
(methanol), mp 79-80 °C; ms: m/z 226 (M ); ir: 3100, 3060,
1-(2-Chlorophenyl)-1H-pyrazolo[3,4-b]quinoxaline (11d).
This compound was obtained from 10d in 36% yield as yellow
+
+
2980, 2925, 2905, 2825, 1560, 1495, 1480, 1415, 1390, 1355,
1350, 1300, 1235, 1170, 1110, 1035, 1000, 905, 845. 830, 780,
needles (ethanol), mp 133.5-134.5 °C; ms: m/z 280 (M ), 282
+
(M +2); ir: 3080, 3066, 1588, 1575, 1565, 1490, 1470, 1380,
1
605, 420; H nmr (deuteriochloroform): δ 8.44 (s, 1H, 3-H),
1350, 1225, 1205, 1125, 1095, 1070, 1045, 990, 835, 750, 730,
13
8.17-7.67 (m, 4H, aromatic), 1.92 (s, 9H, tert-butyl-H); C nmr
1
660, 600, 420; H nmr (deuteriochloroform): δ 8.73 (s, 1H, 3-H),
(deuteriochloroform): δ 142.2, 140.8, 140.6, 137.4, 131.7, 130.0,
129.9, 129.1, 127.5, 60.69, 28.90 (3).
13
8.30-7.48 (m, 8H, aromatic); C nmr (deuteriochloroform): δ
142.9, 141.9, 141.7, 137.0, 135.8, 135.4, 132.3, 131.1, 130.8,
130.4, 130.3, 129.7, 128.9, 128.3, 127.7.
Anal. Calcd. for C
H N : C, 69.00; H, 6.24; N, 24.76.
13 14 4
Found: C, 69.07; H, 6.30; N, 25.04.
Anal. Calcd. for C H ClN : C, 64.18; H, 3.23; N, 19.96.
15
9
4
Found: C, 64.31; H, 3.28; N, 19.93.
1,3-Dimethyl-1H-pyrazolo[3,4-b]quinoxaline (12a).
1-(3-Chlorophenyl)-1H-pyrazolo[3,4-b]quinoxaline (11e).
This compound was obtained from 6b and methylhydrazine
sulphate (10a) in 73% yield as yellow needles (cyclohexane), mp
137-138 °C; ms: m/z 198 (M ); ir: 2930, 1620,1580,1510, 1500,
This compound was obtained from 10e in 44% yield as yellow
+
needles (1,2-dimethoxyethane), mp 152-153 °C; ms: m/z280
1400, 1380, 1350, 1260, 1245, 1185, 1125, 1050, 960, 900, 845,
+
+
(M ), 282 (M +2); ir: 3100, 3030, 1600, 1590, 1570, 1560, 1540,
1520, 1485, 1465, 1415, 1380, 1350, 1250, 1220, 1120, 1100,
1
765, 725, 655, 630, 605, 420; H nmr (deuteriochloroform): δ
8.19-7.63 (m, 4H, aromatic), 4.12 (s, 3H, 1-CH ), 2.75 (s, 3H,
3
1
1075, 945, 855, 770, 755, 735, 670, 660, 420; H nmr (deuterio-
13
3-CH ); C nmr (deuteriochloroform): δ 142.7, 141.8, 141.4,
140.3, 136.0, 130.4, 130.1, 128.3, 127.0, 33.60, 11.47.
3
chloroform): δ 8.57 (s, 1H, 3-H), 8.48-7.23 (m, 8H,aromatic);
13
C nmr (deuteriochloroform): δ 141.9, 141.3, 140.2, 138.0,
Anal. Calcd. for C
H N : C, 66.65; H, 5.08; N, 28.26.
11 10 4
135.7, 134.9, 131.2, 130.1 (3), 129.1, 128.6, 125.7, 119.5, 117.4.
Found: C, 66.43; H, 5.38; N, 28.35.
Anal. Calcd. for C H ClN : C, 64.18; H, 3.23; N, 19.96.
15
9
4
1-tert-Butyl-3-methyl-1H-pyrazolo[3,4-b]quinoxaline (12b).
Found: C, 64.30; H, 3.27; N, 19.68.
This compound was obtained from 6b and tert-butylhydrazine
hydrochloride (10b) in 81% yield as yellow needles (ethanol), mp
159.5-160.5 °C; ms: m/z 240 (M ); ir: 3070, 2980, 2930, 2870,
1-(4-Chlorophenyl)-1H-pyrazolo[3,4-b]quinoxaline (11f).
This compound was obtained from 10f in 62% yield as yellow
+
+
needles (dimethylformamide), mp 197-198 °C; ms: m/z280 (M ),
1960, 1620, 1515, 1500, 1475, 1425, 1375, 1310, 1395, 1310,
1240, 1205, 1150, 1130, 1205, 995, 805, 755, 725, 665, 615, 600,
+
282 (M +2); ir: 3110, 3060, 1600, 1580, 1570, 1560, 1540, 1500,
1430, 1380, 1330, 1250, 1220, 1120, 1105, 1065, 970, 905, 855,
1
620, 415; H nmr (deuteriochloroform): δ 8.22-7.65 (m, 4H,
1
750, 730, 685, 665, 605, 420; H nmr (deuteriochloroform): δ
13
aromatic), 2.80 (s, 3H, 3-CH ), 1.90 (s, 9H, tert-butyl); C nmr
3
8.93 (s, 1H, 3-H), 8.55-7.47 (m, 8H, aromatic).
(deuteriochloroform): δ 143.0, 141.0, 140.4, 140.0, 136.9, 129.9,
129.9, 129.0, 127.0, 60.04, 29.02, 11.61.
Anal. Calcd. for C H ClN : C, 64.18; H, 3.23; N, 19.96.
15
9
4
Found: C, 63.99; H, 3.07; N, 19.63.
Anal. Calcd. for C
H N : C, 69.97; H, 6.71; N, 23.31.
14 16 4
Found: C, 69.81; H, 6.50; N, 23.57.
1-(4-Nitrophenyl)-1H-pyrazolo[3,4-b]quinoxaline (11g).
General Procedure for the Reaction of Oxime 6a with Arylhydra-
zines 10c-g.
This compound was obtained from 10g in 48% yield as yellow
needles (pyridine), mp 310-311 °C; ms: m/z 291 (M ); ir: 3080,
+
1596, 1564, 1548, 1518, 1504, 1482, 1430, 1388, 1334, 1236,
1216, 1166, 1148, 1114, 1068, 970, 908, 804, 850, 766, 748, 730,
684, 608, 548, 528, 496, 422.
A solution of the appropriate arylhydrazine 10c-g (11 mmoles)
or corresponding hydrochloride in acetic acid was added to a
solution of 1.73 g (10 mmoles) of oxime 6a in 100 ml of acetic
acid at 80 °C. After the addition of 5 ml of a 60% aqueous
solution of perchloric acid, the mixture was heated at reflux for
30-60 minutes. The products, precipitate directly at room
temperature or after the addition of water, were collected by
filtration and washed with water.
Anal. Calcd. for C H N O : C, 61.86; H, 3.11; N, 24.04.
15
9 5 2
Found: C, 61.74; H, 3.05; N, 24.25.
General Procedure for the Reaction of Oxime 6b with
Arylhydrazines 10c-h.
A solution of the appropriate arylhydrazines 10c-h
(10.5 mmoles) or corresponding hydrochloride in acetic acid was
added to a solution of 1.87 g (10 mmoles) of oxime 6b in 30 ml of
acetic acid at 80 °C. After the addition of 5 ml of 37% hydrochloric
acid, the mixture was heated at reflux for 15-30 minutes. The prod-
ucts, precipitated directly at room temperature or after the addition
of water, were collected by filtration and washed with water.
1-Phenyl-1H-pyrazolo[3,4-b]quinoxaline (11c).
This compound was obtained from 10c in 53% yield as yellow
needles (50% aqueous acetic acid), mp 147-149 °C; ms: m/z 246
+
(M ); ir: 3090, 3063, 1700, 1652, 1599, 1576, 1501, 1427, 1391,
1360, 1214, 1166, 1120, 1088, 1055, 1009, 970, 905, 850, 804,
1
750, 689, 672, 608, 532, 500, 421; H nmr (deuteriochloroform):

Jul-Aug 2001
Quinoxalines X. A New and Convenient Synthesis
833
3-Methyl-1-phenyl-1H-pyrazolo[3,4-b]quinoxaline (12c).
This compound was obtained from 10c in 73% yield as yellow
1-(4-Bromophenyl)-3-methyl-1H-pyrazolo[3,4-b]quinoxaline
(12h).
+
This compound was obtained from 10h in 77% yield as yellow
needles (ethanol), mp 134-135 °C; ms: m/z 260 (M ); ir: 3065,
+
needles (butanol), mp 241-242 °C; ms: m/z 338 (M ), 340
2950, 2920, 1600, 1570, 1505, 1480, 1450, 1380, 1355, 1335,
1250, 1240, 1200, 1130, 1115, 1075, 1060, 1035, 1000, 900, 840,
+
(M +2); ir: 3112, 3060, 2905, 1586, 1568, 1526, 1494, 1448,
1
1410, 1384, 1356, 1240, 1200, 1122, 1090, 1064, 1010, 926, 826,
764, 732, 672, 602, 504, 476, 422.
750, 740, 690, 675, 660, 600, 500, 460, 402; H nmr (deuterio-
chloroform): δ 8.39-7.25 (m, 9H, aromatic), 2.80 (s, 3H, Me);
Anal. Calcd. for C H BrN : C, 56.66; H, 3.27; N, 16.52.
13
16 11
4
C nmr (deuteriochloroform): δ 144.1, 142.3, 141.3, 140.5,
Found: C, 56.28; H, 3.20; N, 16.71.
139.3, 137.5, 130.6, 130.0, 129.0 (2), 128.8, 127.7, 125.1, 119.3
(2), 11.6.
General Procedure for the Synthesis of the Acylhydrazones 2i-k.
Anal. Calcd. for C
H N : C, 73.83; H, 4.64; N, 21.53.
16 12 4
A solution of the appropriate benzohydrazides 10i-k
(22 mmoles) was added to a solution of 3.44 g (20 mmoles) of
2-sacetylquinoxaline (3b) in 50 ml of hot ethanol. The mixture
was heated at reflux until thin layer chromatography indicated
complete conversion, kept in a refrigerator overnight, and the
precipitate was collected by filtration.
Found: C, 73.54; H, 4.74; N, 21.42.
1-(2-Chlorophenyl)-3-methyl-1H-pyrazolo[3,4-b]quinoxaline
(12d).
This compound was obtained from 10d in 54% yield as yel-
low needles (cyclohexane), mp 155-156 °C; ms: m/z 293
+
+
N'-[1-(Quinoxalin-2-yl)ethylidene]benzohydrazide (2i).
(M ), 295 (M +2); ir: 3060, 2985, 2955, 1590, 1565, 1495,
1475, 1450, 1380, 1355, 1270, 1240, 1200, 1130, 1100, 1080,
This compound was obtained from benzohydrazide (10i) in
1
1050, 1000, 840, 720, 660, 610, 600; H nmr (deuteriochloro-
form): δ 8.28-7.44 (m, 8H, aromatic), 2.89 (s, 3H, CH );
88% yield as colorless needles (toluene), mp 230-231 °C; ms:
13
C
+
3
m/z 290 (M ); ir: 3185, 3060, 1665, 1605, 1550, 1485, 1430,
nmr (deuteriochloroform): δ 144.7, 143.5, 141.7, 140.9,
136.7, 135.5, 132.1, 130.8, 130.7, 130.2, 130.0, 129.6, 128.7,
127.7, 127.6, 11.7.
1380, 1310, 1230, 1150, 1080, 1050, 955, 940, 790, 755, 735,
1
630, 600; H nmr (deuteriochloroform): δ 9.30 (s, 1H, 3-H),
8.19-7.50 (m, 9H, aromatic).
Anal. Calcd. for C H ClN : C, 65.21; H, 3.76; N, 19.01.
Anal. Calcd. for C
H N O: C, 70.33; H, 4.86; N, 19.30.
16 11
4
17 14 4
Found: C, 65.14; H, 3.88; N, 19.08.
Found: C, 70.43; H, 4.70; N, 19.48.
1-(3-Chlorophenyl)-3-methyl-1H-pyrazolo[3,4-b]quinoxaline (12e).
This compound was obtained from 10e in 62% yield as yellow
N'-[1-(Quinoxalin-2-yl)ethylidene]-2-chlorobenzohydrazide (2j).
This compound was obtained from 2-chlorobenzohydrazide
(10j) in 63% yield as colorless needles (ethanol), mp 197-198 °C;
+
needles (n-heptane), mp 138-140 °C; ms: m/z 293 (M ), 295
+
+
+
ms: m/z 324 (M ), 326 (M +2);. ir: 3185, 3060, 1665, 1605,
1550, 1485, 1430, 1380, 1310, 1230, 1150, 1080, 1050, 955, 940,
(M +2); ir: 3100, 3075, 1595, 1560, 1515, 1485, 1380, 1355,
1235, 1200, 1125, 1105, 1070, 940, 860, 770, 750, 740, 725, 670,
1
1
790, 755, 735, 630, 600; H nmr (deuteriochloroform): δ 10.23
600; H nmr (deuteriochloroform): δ 8.33-7.14 (m, 8H,
13
(s, 1H, N-H), 9.01 (s, 1H, 3-H), 8.14-7.37 (m, 8H, aromatic), 2.59
aromatic), 2.71 (s, 3H, CH ); C nmr (deuteriochloroform): δ
3
13
(s, 3H, CH ); C nmr (deuteriochloroform): δ 149.1, 143.4,
144.6, 142.1, 140.9, 140.4, 140.1, 137.4, 134.6, 130.7, 129.9,
129.9, 128.7, 127.9, 124.7, 118.6, 116.5, 11.5.
3
141.7, 141.2, 134.8, 131.2, 130.9, 130.4, 130.1, 130.0 (2), 129.5
(2), 128.9, 128.8, 126.6, 10.5.
Anal. Calcd. for C H ClN : C, 65.21; H, 3.76; N, 19.01.
16 11
4
Anal. Calcd. for C
H ClN O: C, 62.87; H, 4.03; N, 17.25.
17 13 4
Found: C, 65.23; H, 3.79; N, 19.12.
Found: C, 63.03; H, 4.20; N, 17.50.
1-(4-Chlorophenyl)-3-methyl-1H-pyrazolo[3,4-b]quinoxaline
(12f).
N'-[1-(Quinoxalin-2-yl)ethylidene]-4-chlorobenzohydrazide (2k).
This compound was obtained from 4-chlorobenzhydrazide
(10k) in 54% yield as colorless needles (dimethylformamide),
This compound was obtained from 10f in 58% yield as yellow
+
needles (toluene), mp 236-236.5 °C; ms: m/z 293 (M ), 295
+
+
mp 238-240 °C; ms: m/z 324 (M ), 326 (M +2); ir: 3365, 3050,
3030, 1675, 1590, 1515, 1485, 1430, 1400, 1355, 1255, 1150,
+
(M +2); ir: 3116, 3058, 2920, 1594, 1564, 1524, 1496, 1478,
1448, 1414, 1384,1356, 1240, 1200, 1122, 1092, 1062, 1012,
830, 760, 604, 506, 422.
1
1120, 1095, 1010, 950, 830, 750, 680, 565, 520, 495; H nmr
(deuteriochloroform): δ 9.23 (s, 1H, 3-H), 8.12-7.49 (m, 8H,
Anal. Calcd. for C H ClN : C, 65.21; H, 3.76; N, 19.01.
16 11
4
aromatic), 2.60 (s, 3H, CH ).
3
Found: C, 65.22; H, 3.80; N, 18.91.
Anal. Calcd. for C
H ClN O: C, 62.87; H, 4.03; N, 17.25.
17 13 4
Found: C, 62.72; H, 4.09; N, 17.46.
3-Methyl-1-(4-nitrophenyl)-1H-pyrazolo[3,4-b]quinoxaline
(12g).
General Procedure for the Cyclization of the Acylhydrazones
2i-k with p-Chloranil.
This compound was obtained from 10g in 76% yield as yellow
needles (toluene), mp 242-243 °C; ms: m/z 305 (M ); ir: 3116,
+
A mixture of 2.70 g (11 mmoles) of p-chloranil and of the
appropriate acylhydrazones 2i-k (10 mmoles) in 200 ml of
p-xylene was heated at reflux for 12 hours. The solvent was
removed in vacuo and the residue was washed with methanol,
two times with 1 N potassium hydroxide solution, with water and
again with methanol and recrystallized.
1596, 1568, 1505, 1480, 1444, 1418, 1382, 1333, 1259, 1238,
1203, 1120, 1112, 1092, 1064, 1008, 852, 832, 764, 748, 732,
603, 499, 420.
Anal. Calcd. for C H N O : C, 62.95; H, 3.63; N, 22.94.
16 11
5 2
Found: C, 62.29; H, 3.54; N, 23.18.

834
G. Sarodnick and T. Linker
Vol. 38
1-Benzoyl-3-methyl-1H-pyrazolo[3,4-b]quinoxaline (12i).
This compound was obtained from 2i in 36% yield as colorless
13
aromatic), 2.80 (s, 3H, 3-CH ); C nmr (deuteriochloroform): δ
3
166.2, 148.5, 144.6, 141.7, 141.7, 138,2, 132.7, 132.5, 131.5,
131.0 (2), 130.0, 129.7, 129.4, 127.9 (2), 11.8.
H N O: C, 70.82; H, 4.19; N, 19.43.
Found: C, 71.01; H, 4.15; N, 19.31.
+
needles (butanol), mp 201-201.5 °C; ms: m/z 288 (M ); ir: 3058,
Anal. Calcd. for C
17 12 4
2917, 1704, 1598, 1576, 1534, 1496, 1450, 1416, 1388, 1344,
1308, 1228, 1184, 1164, 1130, 1112, 1036, 992, 904, 874, 850,
1
828, 798, 768, 716, 698, 670, 618, 602, 500, 560, 418; H nmr
1-(2-Chlorobenzoyl)-3-methyl-1H-pyrazolo[3,4-b]quinoxaline
(12j).
(deuteriochloroform): δ 8.34-7.53 (m, 9H, aromatic), 2.80 (s, 3H,
13
3-CH ); C nmr (deuteriochloroform): δ 166.2, 148.5, 144.6,
3
This compound was obtained from 2-chlorobenzoyl chloride
in 58% yield as colorless needles (butanol), mp 192-194 °C; ms:
m/z 322 (M ), 324 (M +2); ir: 3068, 2928, 1716, 1618, 1590,
1572, 1542, 1502, 1474, 1440, 1414, 1392, 1348, 1312, 1286,
1260, 1172, 1112, 1064, 1024, 1000, 906, 866, 852, 826, 768,
732, 716, 674, 650, 608, 442, 416; H nmr (deuteriochloroform):
δ 8.28-7.46 (m, 8H, aromatic), 2.74 (s, 3H, 3-CH ); C nmr
(deuteriochloroform): δ 164.6, 149.8, 143.8, 141.7, 141.5, 138.5,
134.3, 131.6, 131.6, 131.5, 129.8, 129.6, 129.5 (2), 129.3, 126.6,
11.7.
141.7, 141.7, 138,2, 132.7, 132.5, 131.5, 131.0 (2), 130.0, 129.7,
129.4, 127.9 (2), 11.8.
+
+
Anal. Calcd. for C
H N O: C, 70.82; H, 4.19;
17 12 4
N,19.43.Found: C, 70.77; H, 4.15; 19.29.
1-(2-Chlorobenzoyl)-3-methyl-1H-pyrazolo[3,4-b]quinoxaline
(12j).
1
13
3
This compound was obtained from 2j in 44% yield as color-
+
less needles (butanol), mp 192-194 °C; ms: m/z 322 (M ), 324
+
(M +2); ir: 3068, 2928, 1716, 1618, 1590, 1572, 1542, 1502,
1474, 1440, 1414, 1392, 1348, 1312, 1286, 1260, 1172, 1112,
1064, 1024, 1000, 906, 866, 852, 826, 768, 732, 716, 674,
Anal. Calcd. for C H ClN O: C, 63.26; H, 3.43; N, 17.36.
Found: C, 63.43; H, 3.49; N, 17.28.
17 11
4
1
650, 608, 442, 416; H nmr (deuteriochloroform): δ 8.28-7.46
1-(4-Chlorobenzoyl)-3-methyl-1H-pyrazolo[3,4-b]quinoxaline
(12k).
13
(m, 8H, aromatic), 2.74 (s, 3H, 3-CH ); C nmr (deuterio-
3
chloroform): δ 164.6, 149.8, 143.8, 141.7, 141.5, 138.5,
134.3, 131.6, 131.6, 131.5, 129.8, 129.6, 129.5 (2), 129.3,
126.6, 11.7.
This compound was obtained from 4-chlorobenzoyl chloride
in 46% yield as colorless needles (2-methoxyethanol), mp
Anal. Calcd. for C H ClN O: C, 63.26; H, 3.43; N, 17.36.
+
+
17 11
4
197.5-198.5 °C; ms: m/z 322 (M ), 324 (M +2); ir: 3060, 2922,
1712, 1618, 1586, 1536, 1486, 1416, 1346, 1308, 1228, 1166,
1112, 1084, 1030, 994, 906, 828, 768, 740, 676, 622, 600, 574,
Found: C, 63.43; H, 3.49; N, 17.28.
1-(4-Chlorobenzoyl)-3-methyl-1H-pyrazolo[3,4-b]quinoxaline
(12k).
1
530, 482, 418; H nmr (deuteriochloroform): δ 8.34-7.49 (m, 8H,
13
aromatic), 2.80 (s, 3H, 3-CH ); C nmr (deuteriochloroform): δ
3
This compound was obtained from 2k in 48% yield as
colorless needles (2-methoxyethanol), mp 197.5-198.5 °C; ms:
165.0, 148.9, 144.6, 141.8 (2), 139.0, 138.2, 132.5 (2), 131.7,
131.0, 130.0, 129.7, 129.5, 128.3 (2), 11.8.
+
+
m/z 322 (M ), 324 (M +2); ir: 3060, 2922, 1712, 1618, 1586,
1536, 1486, 1416, 1346, 1308, 1228, 1166, 1112, 1084, 1030,
Anal. Calcd. for C H ClN O: C, 63.26; H, 3.43; N, 17.36.
17 11
4
Found: C, 63.11; H, 3.39; N, 17.22.
1
994, 906, 828, 768, 740, 676, 622, 600, 574, 530, 482, 418; H
nmr (deuteriochloroform): δ 8.34-7.49 (m, 8H, aromatic), 2.80
General Procedure for the Alkylation of the 1-Unsubstituted
Flavazole 7b.
13
(s, 3H, 3-CH ); C nmr (deuteriochloroform): δ 165.0, 148.9,
3
144.6, 141.8 (2), 139.0, 138.2, 132.5 (2), 131.7, 131.0, 130.0,
129.7, 129.5, 128.3, 11.8.
A mixture of 1.84 g (10 mmoles) of the flavazole 7b, 15
mmoles of the appropriate halogen compound and 2.76 g
(20 mmoles) of anhydrous potassium carbonate in 50 ml of
2-butanone was heated at reflux for 8 hours. The hot solution was
filtered and the residue was washed two times with 30 ml of hot
2-butanone. The filtrates were combined, concentrated in vacuo
and 60 ml of 10% sodium hydroxide solution was added to the
residue. The product was collected by filtration, washed with
water and recrystallized.
Anal. Calcd. for C H ClN O: C, 63.26; H, 3.43; N, 17.36.
17 11
4
Found: C, 63.18; H, 3.48; N, 17.43.
General Procedure for the Acylation of the 1-Unsubstituted
Flavazole 7b.
The appropriate benzoyl chloride 25 mmoles was added drop-
wise to a solution of 1.84 g (10 mmoles) of the flavazole 7b in
40 ml of pyridine at – 15 °C. The mixture was stirred and heated
slowly during 30 minutes until reflux. Reflux was continued for
5 minutes, and the solution was cooled to room temperature and
poured onto 100 g of ice. After one hour the product was
collected by filtration, washed with 40 ml of water and 20 ml of
ethanol and recrystallized.
1,3-Dimethyl-1H-pyrazolo[3,4-b]quinoxaline (12a).
This compound was obtained from the reaction of compound
7b with methyl iodide in 65% yield as yellow needles (cyclo-
+
hexane), mp 137-138 °C; ms: m/z 198 (M ); ir: 2930,
1620,1580,1510, 1500, 1400, 1380, 1350, 1260, 1245, 1185,
1-Benzoyl-3-methyl-1H-pyrazolo[3,4-b]quinoxaline (12i).
1
1125, 1050, 960, 900, 845, 765, 725, 655, 630, 605, 420; H nmr
(deuteriochloroform): δ 8.19-7.63 (m, 4H, aromatic), 4.12 (s, 3H,
This compound was obtained from benzoyl chloride in 55%
yield as colorless needles (butanol), mp 201-201.5 °C; ms: m/z
288 (M ); ir: 3058, 2917, 1704, 1598, 1576, 1534, 1496, 1450,
13
1-CH ), 2.75 (s, 3H, 3-CH ); C nmr (deuteriochloroform): δ
3
3
+
142.7, 141.8, 141.4, 140.3, 136.0, 130.4, 130.1, 128.3, 127.0,
33.60, 11.47.
1416, 1388, 1344, 1308, 1228, 1184, 1164, 1130, 1112, 1036,
992, 904, 874, 850, 828, 798, 768, 716, 698, 670, 618, 602, 500,
Anal. Calcd. for C
H N : C, 66.65; H, 5.08; N, 28.26.
11 10 4
1
560, 418; H nmr (deuteriochloroform): δ 8.34-7.53 (m, 9H,
Found: C, 66.43; H, 5.38; N, 28.35.

Jul-Aug 2001
Quinoxalines X. A New and Convenient Synthesis
835
1-Ethyl-3-methyl-1H-pyrazolo[3,4-b]quinoxaline (12l).
1-Allyl-3-methyl-1H-pyrazolo[3,4-b]quinoxaline (12p).
This compound was obtained from the reaction of
This compound was obtained from the reaction of
compound 7b with ethyl iodide in 59% yield as yellow
needles (cyclohexane), mp 97-98 °C; ms: m/z 212 (M ); ir:
compound 7b with allyl bromide in 65% yield as yellow
needles (hexane), mp 88-90 °C; ms: m/z 224 (M ); ir: 3084,
+
+
3036, 2972, 2932, 1950, 1734, 1618, 1580, 1514, 1482, 1464,
1376, 1356, 1324, 1302, 1248, 1230, 1182, 1124, 1086, 1058,
994, 970, 932, 844, 864, 726, 656, 626, 608, 558, 426; H nmr
3018, 2918, 1646, 1618, 1582, 1560ß, 1514, 1498, 1482,
1464, 1416, 1388, 1350, 1320, 1286, 1246, 1224, 1184, 1122,
1062, 996, 932, 842, 766, 714, 648, 602, 562, 532, 424; H
1
1
(deuteriochloroform): δ 8.23-7.64 (m, 4H, aromatic), 4.59
nmr (deuteriochloroform): δ 8.24-7.65 (m, 4H, aromatic),
(q, J = 7.2 Hz, 2H, CH -CH ), 2.80 (s, 3H, 3-CH ), 1.58 (t, J =
3
2
3
6.12 (m, 1H, CH -CH=CH ), 5.29-5.15 (m, 4H, CH -
2
2
2
13
7.2 Hz, 3H, CH -CH ); C nmr (deuteriochloroform): δ
3
2
CH=CH , 2.81 (s, 3H, 3-CH ).
2)
3
142.2, 141.8, 141.4, 140.5, 136.3, 130.4, 130.1, 128.3, 127.0,
41.85, 14.71, 11.60.
Anal. Calcd. for C
H N : C, 69.62; H, 5.39; N, 24.98.
13 12 4
Found: C, 69.48; H, 5.44; N, 25.21.
Anal. Calcd. for C
H N : C, 67.91; H, 5.10; N, 26.39.
12 12 4
Ethyl (3-methyl-1H-pyrazolo[3,4-b]quinoxalin-1-yl)acetate
(12q).
Found: C, 67.73; H, 5.15; N, 26,24.
1-Isopropyl-3-methyl-1H-pyrazolo[3,4-b]quinoxaline (12m).
This compound was obtained from ethyl bromoacetate in 78%
yield as yellow needles (ethanol), mp 164-165.5 °C; ms: m/z 270
(M ); ir: 2988, 2938, 1748, 1580, 1500, 1474, 1460, 1378, 1348,
This compound was obtained from the reaction of compound
7b with 2-iodopropane in 76% yield as yellow needles (hexane),
+
+
mp 102-103.5 °C; ms: m/z 226 (M ); ir: 3068, 2974, 2930, 2874,
1322, 1286, 1218, 1184, 1122, 1028, 902, 932, 874, 774, 743,
1572, 1500, 1482, 1456, 1382, 1364, 1350, 1312, 1234, 1198,
1136, 1114, 1060, 970, 906, 842, 758, 730, 676, 622, 608, 542,
1
728, 684, 646, 602, 568, 426; H nmr (deuteriochloroform): δ
8.27-7.68 (m, 4H, aromatic), 5.32 (s, 2H, N-CH ), 4.23 (qu, J =
1
2
466, 422; H nmr(deuteriochloroform): δ 8.25-7.64 (m, 4H,
7.14 Hz, 2H, CH -CH ), 2.81 (s, 3H, 3-CH ), 1.27 (t, J = 7.14,
3
2
3
aromatic), 5.34 (qu, J = 6.7 Hz, 1H, H C-CH-CH ), 2.82 (s, 3H,
3
3
13
13
3H, CH -CH ); C nmr (deuteriochloroform): δ 168.0, 143.7,
3-CH ), 1.64 (d, J = 6.7 Hz, 6H, H C-CH-CH ); C nmr
3
2
3
3
3
143.4, 141.5, 140.8, 136.6, 130.7, 130.2, 128.4, 127.5, 61.73,
47.97, 14.02, 11.69.Anal. Calcd. for C N O : C, 62.21; H,
(deuteriochloroform): δ 142.0, 141.7, 141.4, 140.6, 136.5, 130.3,
130.1, 128.4, 127.0, 48.5, 21.8 (2), 11.7.
H
14 14
4 2
5.22; N, 20.73. Found: C, 62.14; H, 5.31; N, 20.65.
Anal. Calcd. for C
H N : C, 69.00; H, 6.24; N, 24.76.
13 14 4
Found: C, 69.14; H, 6.28; N, 24.64.
Ethyl 2-(3-methyl-1H-pyrazolo[3,4-b]quinoxalin-1-yl)propi-
onate (12r).
1-Butyl-3-methyl-1H-pyrazolo[3,4-b]quinoxaline (12n).
This compound was obtained from the reaction of
This compound was obtained from the reaction of
compound 7b with 1-iodobutane in 48% yield as yellow
needles (hexane), mp 57-60 °C; ms: m/z 240 (M ); ir: 3058,
compound 7b with ethyl 2-bromopropionate in 69% yield as
yellow needles (ethanol), mp 87-89 °C; ms: m/z 284 (M ); ir:
+
+
2952, 2928, 2868, 1618, 1578, 1560, 1498, 1482, 1464, 1414,
1376, 1350, 1324, 1242, 1222, 1182, 1122, 1070, 1012, 976,
922, 758, 726, 694, 638, 602, 422; H nmr (deuterio-
2986, 2916, 1578, 1500, 1480, 1452, 1386, 1348, 1294, 1210,
1196, 1156, 1136, 1122, 1086, 1034, 964, 890, 864, 766, 728,
702, 670, 638, 600, 540, 464, 424; H nmr (deuterio-
1
1
chloroform): δ 8.25-7.66 (m, 4H, aromatic), 4.54 (t, J =7.2 Hz,
chloroform): δ 8.28-7.69 (m, 4H, aromatic), 5.78 (q, J = 7.4
2H, N-CH ), 1.99 (q, J = 7.4 Hz, 2H, CH -CH -CH -CH ),
2
3
2
2
2
Hz, 1H, N-C-H), 4.18 (q, J = 7.1 Hz, 2H, Ester-CH ), 2.83
2
1.39 (sx, J = 7.5 Hz, 2H, CH -CH -CH -CH ), 0.97 (t, J = 7.4
3
2
2
2
(s, 3H, 3-CH ) 2.02 (d, J = 7.4, 3H, CH -CH-), 1.18 (t, J = 7.1,
3
3
13
Hz, 3H, CH -CH -CH -CH ); C nmr (deuteriochloroform):
13
3
2
2
2
3H, Ester-CH ); C nmr (deuteriochloroform): δ 181.7,
3
δ 142.6, 141.8, 141.6, 140.5, 136.2, 130.3, 130.1, 128.4,
127.0, 46.67, 31.51, 19.91, 13.59, 11.61.
170.5, 143.2, 141.4, 140.9, 136.7, 130.6, 130.2, 128.4, 127.3,
61.61, 54.39, 16.13, 13.96, 11.71.
Anal. Calcd. for C
H N : C, 69.97; H, 6.71; N, 23.31.
14 16 4
Anal. Calcd. for C
H N O : C, 63.37; H, 5.67; N, 19.71.
15 16 4 2
Found: C, 70.21; H, 6.85; N, 23.19.
Found: C, 63.47; H, 5.76; N, 19.55.
1-Isobutyl-3-methyl-1H-pyrazolo[3,4-b]quinoxaline (12o).
1-Benzyl-3-methyl-1H-pyrazolo[3,4-b]quinoxaline (12s).
This compound was obtained from the reaction of
This compound was obtained from the reaction of compound
compound 7b with 2-bromobutane in 42% yield as yellow
7b with benzyl bromide in 37% yield as yellow needles (hexane),
+
needles (hexane), mp 81-83 °C; ms: m/z 240 (M ); ir: 3044,
+
mp 156-158 °C; ms: m/z 274 (M ); ir: 3064, 2918, 1684, 1604,
2960, 2926, 2872, 2360, 1940, 1844, 1734, 1618, 1576, 1560,
1510, 1498, 1484, 1466, 1430, 1404, 1386, 1352, 1320, 1286,
1246, 1226, 1182, 1122, 1072, 986, 942, 880, 842, 764, 7289,
1578, 1512, 1498, 1480, 1456, 1382, 1352, 1316, 1266, 1240,
1206, 1178, 1120, 1104, 1072, 982, 930, 904, 842, 760, 730, 712,
1
680, 638, 618, 604, 576, 422; H nmr (deuteriochloroform): δ
1
708, 642, m 622, 600; H nmr (deuteriochloroform): δ
8.20-7.58 (m, 4H, aromatic/quinoxaline) 7.37-7.17 (m, 5H,
8.25-7.66 (m, 4H, aromatic), 4.35 (d, J = 7.4 Hz, 2H, N-CH ),
2
aromatic/phenyl), 5.68 (s, 2H, benzyl-CH ), 2.75 (s, 3H, 3-CH );
2.81 (s, 3H, 3-CH ), 2.47 (m, 1H, isobutyl-CH), 0.97 (d, J =
2
3
3
13
13
C nmr (deuteriochloroform): δ 143.1, 142.9, 141.9, 140.9,
137.0, 136.6, 130.7, 130.4, 128.8, 128.2, 128.2, 128.1, 128.0,
127.9 , 127.4,50.81, 11.95.
6.7, 6H, isobutyl-CH ); C nmr (deuteriochloroform): δ
143.0, 141.7, 141.7, 140.6, 136.1, 130.3, 130.1, 128.5, 127.0,
54.19, 28.93, 20.25, 20.02, 11.63.
3
Anal. Calcd. for C
H N : C, 74.43; H, 5.14; N, 20.42.
Anal. Calcd. for C
H N : C, 69.97; H, 6.71; N, 23.31.
17 14 4
14 16 4
Found: C, 70.13; H, 6.81; N, 23.25.
Found: C, 74.51; H, 5.18; N, 20.38.

836
G. Sarodnick and T. Linker
Vol. 38
1-(4-Chlorobenzyl)-3-methyl-1H-pyrazolo[3,4-b]quinoxaline
(12t).
Acknowledgement.
This work was supported by the Fonds der Chemischen
Industrie and the Deutsche Forschungsgemeinschaft (Li 556/7-2).
This compound was obtained from the reaction of compound
7b with 4-chlorobenzyl chloride in 52% yield as yellow needles
+
+
(ethanol), mp 170-171 °C; ms: m/z 308 (M ), 310 (M +2); ir:
3052, 2920, 1576, 1562, 1516, 1492 1464, 1420, 1408, 1386,
1352, 1320, 1302, 1286, 1244, 1224, 1196, 1180, 1120, 1094,
1012, 988, 928, 904, 814, 770, 718, 692, 642, 602, 556, 482, 462,
REFERENCES AND NOTES
[1] Part IX: G. Sarodnick, L. Hilfert, G. Kempter and
E. Kleinpeter, J. Prakt. Chem., 339, 714 (1997).
1
422; H nmr (deuteriochloroform): δ 8.24-7.22 (m, 8H,
aromatic), 5.65 (s, 2H, CH ), 2.77 (s, 3H, 3-CH ); C nmr
(deuteriochloroform): δ 142.9, 142.8, 141.7, 140.8, 136.4, 135.2,
133.6, 130.6, 130.2, 129.4 (2), 128.7 (2), 128.5, 127.3, 49.9, 11.6.
[2] L. Mester, Angew. Chem., 77, 588 (1965).
13
2
3
[3a] N. P. Buu-Hoi, J.-N. Vallat, G. Saint-Ruf and G. Lambelin,
Chim. Ther., 245 (1971); [b] N. P. Buu-Hoi, J.-N. Vallat, G. Saint-Ruf and
G. Lambelin, Chim. Ther., 210 (1972); [c] Y. Kurasawa, M. Muramatsu,
K. Yamazaki, Y. Okamoto and A. Takada, J. Heterocyclic Chem., 23,
1387 (1986); [d] H. S. Kim, J. Y. Chung, E. K. Kim, Y. T. Park,
Y. S. Hong, M. K. Lee, Y. Kurasawa and A. Takada, J. Heterocyclic
Chem., 33, 1855 (1996).
Anal. Calcd. for C
H ClN : C, 66.13; H, 4.24; N, 18.15.
17 13 4
Found: C, 66.19; H, 4.28; N, 18.06.
3-Methy1-1-(1-phenylethyl)-1H-pyrazolo[3,4-b]quinoxaline
(12u).
[4] G. R. Wendt and K. W. Ledig, US 3.431.262; Chem. Abstr., 70
P 106512d (1969).
This compound was obtained from the reaction of compound
7b with (1-bromoethyl)benzene in 45% yield as yellow needles
[5] Y. Kurasawa, M. Muramatsu, K. Yamazaki, S. Tajima,
Y. Okamoto and A. Takada, J. Heterocyclic Chem., 23, 1379 (1986).
[6] A. Monge, J. A. Palop, A. Pinol, F. J. Martinez-Crespo,
S. Narro, M. Gonzalez, Y. Sainz, A. Lopez de Cerain, E. Hamilton and
A. J. Barker, J. Heterocyclic Chem., 31, 1135 (1994).
[7a] H. Ohle and G. A. Melkonian, Ber. Dtsch. Chem. Ges., 74,
398 (1941); [b] M. A. El-Maghraby, A. I. M. Koraiem, Z. H. Khalil and
R. M. A. El-Hamed, Indian J. Chem., 26B, 52 (1987).
[8a] G. Henseke, W. Dose and K. Dittrich, Angew. Chem., 69, 479
(1957); [b] P. M. Pillai and P. Ramabhadran, Indian J. Chem., 25B, 901
(1986).
[9a] P. M. Pillai and P. Ramabhadran, Indian J. Chem., 25B, 960
(1986); [b] L. Somogyi, Carbohydr. Res., 329, 89 (1992).
[10a] Y. Kurasawa, M. Muramatsu, K. Yamazaki, S. Tajima,
Y. Okamoto and A. Takada, J. Heterocyclic Chem., 23, 633, (1986);
[b] Y. Kurasawa, M. Muramatsu, K. Yamazaki, S. Tajima, Y. Okamoto
and A. Takada, J. Heterocyclic Chem., 23, 959, (1986).
[11a] G. P. Gardini and F. Minisci, J. Chem. Soc., C, 929 (1970);
[b] E. Lippmann, K. Sedelmeyer, E. Engler, N. Scharf, P. Böhme and
G. Ritter, Z. Chem., 18, 177 (1978).
[12] G. Sarodnick and G. Kempter, Z. Chem., 22, 300 (1982).
[13] G. Henseke and W. Lemke, Chem. Ber., 91, 113 (1958).
[14] R. Hayes and O. Meth-Cohn, Tetrahedron Lett., 23, 1613
(1982).
[15a] H. S. Kim, E. K. Kim, S. S. Kim, Y. T. Park, Y. S. Hong and
Y. Kurasawa, J. Heterocyclic Chem., 34, 39 (1997); [b] K. Makino,
H. S. Kim and Y. Kurasawa, J. Heterocyclic Chem. 36, 321 (1999).
+
(heptane), mp 116-118 °C; ms: m/z 288 (M ); ir: 3060, 2976,
2926, 1618, 1574, 1510, 1498, 1478, 1458, 1382, 1348, 1310,
1280, 1240, 1206, 1180, 1144, 1134, 1122, 1090, 1054, 1030,
992, 954, 918, 842, 760, 730, 710, 634, 616, 588, 560, 636, 422;
1
H nmr (deuteriochloroform): δ 8.23-7.20 (m, 9H, arom.), 6.35
(q, 1H, H C-CH),2.81 (s, 3H, 3-CH ), 2.08 (d, 3H, H C-CH);
3
3
3
13
C nmr (deuteriochloroform): δ 142.6, 142.3, 141.7, 141.6,
140.8, 136.7, 130.3, 130.2, 128.6, 128.4 (2), 127.5, 127.1, 126.8
(2), 55.5, 20.4, 11.8.
Anal. Calcd. for C
H N : C, 74.98; H, 5.59; N, 19.43.
18 16 4
Found: C, 75.11; H, 5.64; N, 19.25.
1-(2-Chloropyridin-5-ylmethyl)-3-methyl-1H-pyrazolo[3,4-b]-
quinoxaline (12v).
This compound was obtained from the reaction of compound
7b with 2-chloro-5-chloromethylpyridine in 40% yield as yellow
+
needles (ethanol), mp 163-164 °C; ms: m/z 309 (M ), 311
+
(M +2);ir: 3050, 2920, 1738, 1620, 1566, 1498, 1484, 1424,
1394, 1352, 1318, 1290, 1242, 1224, 1180, 1110, 1020, 986, 950,
1
834, 764, 732, 712, 642, 602, 494, 496, 422; H nmr (deuterio-
chloroform): δ 8.54-7.23 (m, 7H, aromatic), 5.69 (s, 2H, N-CH ),
2
13
2.78 (s, 3H, 3-CH ); C nmr (deuteriochloroform): δ 151.0,
149.4, 143.5, 142.8, 141.6, 140.9, 138.7, 136.5, 131.2, 130.8,
130.3, 128.5, 127.5, 124.2, 47.4, 11.6.
3
Anal. Calcd. for C
H ClN : C, 62.04; H, 3.90; N, 22.61.
16 12 5
Found: C, 61.98; H, 3.95; N, 22.53.