Efficient one-pot synthesis of quinoxalines in the presence of zinc iodide as catalyst

Full text of DOI:10.1134/S1070428009070240

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 7, pp. 1116–1118. © Pleiades Publishing, Ltd., 2009.
Published in Russian in Zhurnal Organicheskoi Khimii, 2009, Vol. 45, No. 7, pp. 1127–1128.
SHORT
COMMUNICATIONS
Efficient One-Pot Synthesis of Quinoxalines in the Presence
of Zinc Iodide as Catalyst*
J. N. Sangshettia, N. D. Kokarea, b, and D. B. Shindea
a Department of Chemical Technology, Dr. Babasahed Ambedkar Marathwada University,
Aurangabad, 431004 India
b Wockhardt Research Centre, Aurangabad, 431210 India
e-mail: dbshinde.2007@gmail.com
Received October 1, 2007
DOI: 10.1134/S1070428009070240
Quinoxaline and its derivatives constitute an impor-
tant class of benzo-fused heterocycles with a broad
spectrum of biological activity, which have made them
privileged structural fragments of pharmacologically
active compounds [1–4]. Quinoxaline derivatives are
generally synthesized by condensation of arene-1,2-di-
amines with 1,2-dicarbonyl compounds in organic sol-
vents under reflux (2–12 h); their yields range from 34
to 85% [5]. Some progress in the synthesis of quinox-
aline derivatives was achieved with the use of bismuth-
catalyzed oxidative coupling [6], tandem oxidation in
the presence of Pd(OAc)2 or RuCl2–(PPh3)3–TEMPO
[7] and MnO2 [8], heteroannulation of nitroketene
N,S-arylaminoacetals with POCl3 [9], solid-phase syn-
thesis over Synphase TM Lanterns [10], cyclization of
arylimino oximes in boiling acetic anhydride [11], con-
densation of o-phenylenediamines with 1,2-dicarbonyl
compounds in MeOH/AcOH under microwave irradia-
tion [12], and molecular iodine-catalyzed cyclocon-
densation [13]. We have reported a procedure with the
use of mercury iodide and lead oxide [14], and Heravi
et al. recently described synthesis of quinoxalines un-
der catalysis by CuSO4·5H2O and Zn[L-proline] [15].
long reaction time, and laborious isolation procedures.
Therefore, development of a mild, efficient, and versa-
tile procedure for the synthesis of quinoxaline deriva-
tives still remains strongly desirable.
In continuation of our studies on the synthesis of
various heterocyclic compounds [16], in the present
communication we describe a simple, mild, and effi-
cient procedure for the preparation of quinoxalines
with the use of zinc iodide as catalyst. In the first step
of our study, we examined the reaction of benzoin with
o-phenylenediamine (Scheme 1) in the presence of
ZnI2 with a view to determine optimal conditions, such
as solvent and amount of ZnI2. Given below are sol-
vent, reaction time (min), and yield (%) of 2,3-di-
phenylquinoxaline in the presence of 10 mol % of
ZnI2: acetonitrile, 50, 90; THF, 70, 75; ethanol, 30, 95;
acetonitrile–water (1:1), 60, 88; ethanol–water (1:1),
30, 95. Thus the optimal conditions include aqueous
ethanol (1:1) as solvent and 10 mol % of the catalyst
(ZnI2). Under these conditions we synthesized a series
of substituted quinoxalines (Scheme 2). The substit-
uents R and R′, reaction time (min), yield (% of the
isolated product), and melting points (published data
[7, 14] are given in parentheses) are listed below: Ph,
H, 30, 92, 80–82 (81–82); Me, H, 30, 86, orange oily
Many of the above methods suffer from one or
more limitations, such as harsh conditions, low yields,
Scheme 1.
H2N
H2N
Ph
Ph
N
N
Ph
Ph
O
ZnI2
+
OH
* The text was submitted by the authors in English.
1116

EFFICIENT ONE-POT SYNTHESIS OF QUINOXALINES
1117
Scheme 2.
H2N
H2N
N
N
R
O
ZnI2
+
R
OH
R'
R'
substance; 2-Fu, H, 45, 95, 102–104 (101–103); cyclo-
hexyl, H, 45, 90, 44–46 (45–46); Ph, 4,5-Me2, 45, 94,
121 (120–123); cyclohexyl, 4,5-Me2, 45, 93, 67 (66–
68); C5H11, 2,3-Me2, 45, 89, orange oily substance;
2,4-Cl2C6H3, H, 30, 84, 125–127 (124–126); 2,4-Cl2-
C6H3, 4,5-Me2, 40, 90, 141–142 (140–142); 4-ClC6H4,
H, 30, 85, 120–122 (118–119); 4-FC6H4, H, 30, 95,
126–129 (126–127).
mass spectra (electrospray ionization) were obtained
on a Waters Micromass Quattro II instrument. All
reagents used were of analytical grade and were not
subjected to additional purification.
The authors are thankful to the Head of the Chem-
ical Technology Department, Dr. Babasaheb Ambedkar
Marathwada University (Aurangabad, 431004 India)
for providing laboratory facilities.
Thus we have developed a simple, efficient, and
ecologically safe procedure for the synthesis of quin-
oxalines from various α-hydroxy ketones and 1,2-di-
amines using inexpensive and readily accessible
zinc(II) iodide as catalyst. In all the above syntheses,
the solvent was aqueous ethanol which may be re-
garded as environmentally benign and conforming to
the “green chemistry” principles. Mild reaction condi-
tions, short reaction time, excellent yields, and easy
workup make the proposed procedure a useful alter-
native to the existing methods.
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