Niobium (V) chloride: An efficient catalyst for the synthesis of quinoxalines

Article abstract of DOI:10.2174/157017810791112432

A simple and efficient method for the synthesis of quinoxalines derivatives has been developed. All the reactions were carried out in presence of niobium (V) chloride at acetonitrile reflux conditions. The method is applicable to a variety of diketones and 1, 2-phenylenediamines to afford the corresponding derivatives in excellent yields.

Full text of DOI:10.2174/157017810791112432

208
Letters in Organic Chemistry, 2010, 7, 208-211
Niobium (V) Chloride: An efficient Catalyst for the Synthesis of
Quinoxalines
Y. Venkateswarlu and P. Leelavathi*
Department of Chemistry, College for Women Koti, Osmania University, Hyderabad-500007, India
Received December 04, 2009: Revised February 04, 2010: Accepted February 06, 2010
Abstract: A simple and efficient method for the synthesis of quinoxalines derivatives has been developed. All the
reactions were carried out in presence of niobium (V) chloride at acetonitrile reflux conditions. The method is applicable
to a variety of diketones and 1, 2-phenylenediamines to afford the corresponding derivatives in excellent yields.
Keywords: Diketones, ortho-phenylenediamines, niobium chloride, quinoxalines.
Quinoxaline derivatives have received considerable
interest from the pharmaceutical point of view because of
their therapeutic prosperities such as anti-bacterial, anti-viral,
anti-inflammatory, anti-cancer, and kinase inhibitors [1-3].
In addition, quinoxaline derivatives have been evaluated as
anthelmintic agents, semiconductors, dyes and biocides [4,
5]. Therefore, a variety of synthetic strategies have been
developed for the preparation of substituted quinoxalines.
Conventionally, quinoxalines synthesis can be achieved by
the reaction of ortho-phenylenediamine with two-carbon
synthones such as ꢀ-dicarbonyls [6-10], ꢀ-halogeno
carbonyls, ꢀ-hydroxycarbonyls, ꢀ-azocarbonyls, epoxides,
and ꢀ, ꢁ-dihalides [11-18]. Among the reported procedures,
amount of niobium pentachloride under mild reaction
conditions.
Accordingly, treatment of 1, 2-phenylenediamine (1)
with benzyl (2) in presence of 20 mol% of niobium
pentachloride in acetonitrile at 80-85 0C afforded 2, 3-
diphenyl quinoxalines (3a) as shown in the Scheme 1. The
reaction was completed within 4.0 hours and the product was
obtained in 94% yield. This observation provided the
incentive for further study of reactions with other ortho-
phenylenediamines and diketocompounds.
Interestingly, various ortho-phenylenediamines such as
pyridine-2, 3-diamine, cyclo hexene-1, 2-diamine and 4, 5-
NH2
O
O
R1
R2
N
N
R1
R2
NbCl5
R
+
R
NH2
CH3CN, reflux
1
3
2
Scheme 1.
the most common method is the condensation of an aryl 1, 2-
di amine with 1,2-diketone compounds in refluxing ethanol
or acetic acid [19-23] or using different catalysts and
reaction conditions [24-29]. However, many of these
methods suffer from several drawbacks, such as drastic
reaction conditions, use of polar solvents (e.g. AcOH, EtOH,
DMSO), expensive and toxic metal catalyst (e.g. Pd(OAc)2
and RuCl2(PPh3)3-TEMPO), tedious work up procedures and
unsatisfactory yields, which limit their use [30, 31].
Therefore, the development of simple, convenient
environmentally benign and improved method for the
synthesis of quinoxalines derivatives would certainly be
useful in generating combinatorial libraries for drug
discovery. In this article, we report a novel method for the
synthesis of quinoxalines derivatives via the coupling of aryl
1, 2-diamines and 1, 2-diketo compounds using a catalytic
dimethylbenzene-1, 2-diamine were reacted smoothly with
benzyl, biacetyl and acenaphthylene-1, 2-dione to give the
corresponding quinoxalines derivatives. Both aromatic and
alicyclic diamines as well as aromatic and aliphatic
diketones were participated well in this conversion (Table 1).
In all cases, the reactions were preceded efficiently in the
0
presence of 20 mol% of niobium pentachloride at 80-85 C
in acetonitrile and the products were obtained in high to
excellent yields. No side products were observed under these
reaction conditions. In general, the condensation takes place
faster, when the reaction was carried out between aromatic
diketones and ortho-phenylenediamines. In a similar manner,
the reaction between aliphatic diketones and alicyclic
diamines was comparatively slower in terms of reaction rates
as well as yields. All the reactions were completed with in
4.0 to 7.0 hours of reaction time at 80-85 0C and the obtained
products yields were in 75 to 95 %. The structures of the
1
products were identified by their H NMR, IR and mass
*Address correspondence to this author at the Department of Chemistry,
College for Women Koti, Osmania University, Hyderabad-500007, India;
Tel: +91-40-24657813; Fax: +91-40-24657813;
spectral data and compared with literature reports.
E-mail: yekkiralavenkat@gmail.com
1570-1786/10 $55.00+.00
© 2010 Bentham Science Publishers Ltd.

Niobium (V) Chloride
Letters in Organic Chemistry, 2010, Vol. 7, No. 3
209
Table 1. Niobium (V) Chloride Catalyzed Synthesis of Quinoxalines
Yieldb (%)
1, 2-Diamine
1, 2-Diketone
Producta
Entry
Reaction Time (h)
NH2
O
Ph
N
Ph
a
4.0
94
89
88
95
84
75
88
86
NH2
O
Ph
N
Ph
NH2
O
Ph
N
Ph
b
c
d
e
f
5.0
6.0
4.0
5.0
7.0
5.0
5.0
N
NH2
O
Ph
N
N
Ph
NH2
O
Ph
N
Ph
NH2
O
Ph
N
Ph
NH2
O
Ph
N
Ph
NH2
NH2
O
Ph
N
Ph
O
N
N
NH2
N
N
O
NH2
O
N
NH2
N
O
NH2
O
N
g
h
NH2
NH2
O
N
O
N
NH2
O
N
O
O
O
O
O
O
O
O
NH2
N
i
j
5.0
5.5
5.0
4.5
86
85
91
92
N
NH2
N
N
NH2
NH2
N
N
NH2
N
N
k
NH2
NH2
N
N
l
NH2
aAll the products were identified by their 1H NMR, IR and mass.
bYields were isolated and unoptimized.

210 Letters in Organic Chemistry, 2010, Vol. 7, No. 3
Venkateswarlu and Leelavathi
Compound (3d)
In summary, we have developed a novel method for the
synthesis of quinoxalines using a catalytic amount of NbCl5
in acetonitrile reflux via the coupling of diketocarbonyls
with 1, 2-diamines. In addition to its simplicity and mild
reaction conditions, this method provides high yields of
products.
IR (KBr): ꢀ 3386, 2939, 2856, 1646, 1428, 1299, 1208,
1108, 1043, 992, 923, 857, 758 cm.-1.; H NMR (CDCl3): ꢁ
1
2.52 (s, 6H), 7.81 (t, 2H, J = 6.0 Hz), 7.90 (s, 2H), 8.20 (d,
2H, J = 6.0 Hz), 8.39 (d, 2H, J = 6.0 Hz).
Compound (3e)
GENERAL PROCEDURE FOR THE SYNTHESIS OF
QUINOXALINES
IR (KBr): ꢀ 3376, 2994, 2947, 1641, 1599, 1560, 1461,
1395, 1313, 1238, 1191, 1151, 1108, 1041, 995, 918, 830,
1
To a mixture of diketone (210mg, 1.0 mmol) and diamine
(128mg, 1.1 mmol) in acetonitrile (5.0 mL) was added the
catalyst NbCl5 (20 % mmol) at room temperature. The
resulting reaction mixture was stirred at reflux condition for
a period of 4.0 to 6.0 hours (as mentioned in the Table 1).
The progress of the reaction was monitored by thin layer
chromatography. After completion of the reaction, as
indicated by TLC, the solvent was removed from the
reaction mixture under reduced pressure. The residue was
extracted with ethyl acetate (2x10 mL). The organic layer
was dried over Na2SO4 and concentrated under reduced
pressure to afford the crude products, which were purified by
column chromatography using silica gel (60-120 mesh). All
796, 713, 680 cm.-1.; H NMR (CDCl3): ꢁ 2.78 (s, 3H), 2.83
(s, 3H), 7.58-7.68 (m, 1H), 8.35 (d, 1H, J = 5.0 Hz), 9.05 (d,
1H, J = 3.0 Hz). EIMS: m/z (%): 159 (m+ 48), 144 (10), 118
(58), 105 (12), 91 (15), 77 (52), 61 (100), 50 (18), 41 (66).
Compound (3g)
IR (KBr): ꢀ 3383, 2940, 2850, 1620, 1563, 1494, 1442,
1399, 1367, 1325, 1255, 1200, 1158, 1113, 1095, 1044, 988,
907, 833, 769, 677 cm-1.; 1H NMR (CDCl3): ꢁ 7.68-7.72 (m,
1H), 7.82-7.90 (m, 2H), 8.12-8.18 (m, 2H), 8.40 (d, 1H, J =
6.0 Hz), 8.01-8.10 (m, 2H), 9.12 (s, 1H). EIMS: m/z (%):
255 (m+ 25), 233 (56), 225 (18), 211 (33), 194 (15), 178
(30), 171 (65), 149 (20), 131 (25), 115 (15), 105 (100), 75
(28).
1
the pure products were identified by their IR, H NMR and
mass spectroscopy data.
Compound (3h)
SPECTRAL DATA FOR SELECTED COMPOUNDS
Compound (3a)
IR (KBr): ꢀ 3380, 2941, 2885, 1647, 1428, 1397, 1324,
1208, 1164, 1111, 1044, 989, 922, 856, 762, 671 cm.-1.; H
1
NMR (CDCl3): ꢁ 2.72 (s, 6H), 7.60-7.70 (m, 2H), 7.90-8.01
(m, 2H). EIMS: m/z (%): 158 (m+ 70), 143 (10), 130 (10),
118 (10), 117 (100), 102 (10), 90 (15), 89 (12), 77 (20), 76
(35), 75 (12), 61 (12), 50 (18), 41 (10).
IR (KBr): ꢀ 3384, 3056, 2934, 1659, 1595, 1541, 1474,
1442, 1394, 1344, 1248, 1216, 1174, 1053, 977, 925, 872,
798, 768, 725, 696 cm.-1 .; 1H NMR (CDCl3): ꢁ 7.25-7.35 (m,
6H), 7.45-7.55 (m, 4H), 7.75 (q, 2H, J = 6.0 Hz), 8.35 (d,
2H, J = 6.0 Hz). EIMS: m/z (%): 283 (m+1 100), 256 (10),
205 (10), 179 (35), 140 (28), 128 (18), 104 (10), 91 (15), 79
(50), 76 (20), 52 (10).
Compound (3l)
IR (KBr): ꢀ 3387, 3064, 2938, 1661, 1592, 1449, 1323,
1211, 1172, 1110, 1045, 996, 927, 874, 794, 719, 681, 641
cm.-1.; 1H NMR (CDCl3): ꢁ 1.48-1.62 (m, 3H), 1.90-2.05 (m,
3H), 2.55 (d, 2H, J = 6.0 Hz), 3.08-3.18 (m, 2H), 7.68 (t, 2H,
J = 6.0 Hz), 7.95 (d, 4H, J = 6.0 Hz).
Compound (3b)
IR (KBr): ꢀ 3413, 3058, 2923, 2853, 1592, 1549, 1433,
1385, 1338, 1242, 1189, 1123, 1070, 1020, 973, 922, 806,
776, 740, 698 cm.-1 .; H NMR (CDCl3): ꢁ 7.25-7.40 (m,
1
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