A facile synthesis of phenazine and quinoxaline derivatives using magnesium sulfate heptahydrate as a catalyst

Article abstract of DOI:10.2298/JSC100801104K

Convenient and simple procedures for the synthesis of phenazine and quinoxaline derivatives were developed via a reaction of o-phenylenediamines and 1,2-dicarbonyl compounds. In addition, the synthesis of two new 1,4-benzodiazine derivatives and the catal

Full text of DOI:10.2298/JSC100801104K

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
J. Serb. Chem. Soc. 76 (9) 1191–1198 (2011)
UDC 547.864+547.856+542.913:544.478
JSCS–4195
Original scientific paper
A facile synthesis of phenazine and quinoxaline derivatives
using magnesium sulfate heptahydrate as a catalyst
*
BAHADOR KARAMI and SAEED KHODABAKHSHI
Department of Chemistry, Yasouj University, Yasouj, Zip Code: 75918-74831,
P. O. Box 353, Iran
(Received 1 August, revised 29 November 2010)
Abstract: Convenient and simple procedures for the synthesis of phenazine and
quinoxaline derivatives were developed via a reaction of o-phenylenediamines and
1,2-dicarbonyl compounds. In addition, the synthesis of two new 1,4-benzodiazine
derivatives and the catalytic activity of magnesium sulfate heptahydrate
(MgSO4·7H2O) in the room temperature condensation of o-phenylenediamines and
1,2-dicarbonyl compounds in ethanol as solvent are reported. This method has
many appealing attributes, such as excellent yields, short reaction times, and simple
work-up procedures.
Keywords: phenazine; quinoxaline; magnesium sulfate heptahydrate; catalyst.
INTRODUCTION
Nitrogen-containing heterocycles, which exhibit extensive biological proper-
1
ties, are abundant in natural compounds. Phenazines and quinoxalines are im-
portant classes of benzoheterocycles, which have significance in both chemistry
2
and biology.
Many phenazine compounds, which are produced by bacteria such as Pseu-
domonas spp., Streptomyces spp. and Pantoea agglomerans, are found in nature
These natural phenazine products have been implicated in the virulence and com-
3,4
petitive fitness of the producing organisms. Quinoxaline and phenazine deriva-
5
6
7
tives constitute the basis of some antitumor agents, bactericides, fungicides,
8
9
herbicides, and insecticides (e.g., quinalphos). In addition, they are used in
dyes, building blocks for the synthesis of organic semiconductors, chemically
controllable switches, cavitands, DNA cleaving agents, dehydroannu-
10
11
12
13
14
15
16–18
lenes, and electrical-photochemical materials.
A number of synthetic strategies have been developed for the preparation of
19
substituted quinoxalines. Many of the existing methods, however, suffer from
*Corresponding author. E-mail: karami@mail.yu.ac.ir
doi: 10.2298/JSC100801104K
1191
Available online at www.shd.org.rs/JSCS/
_________________________________________________________________________________________________________________________
2011 Copyright (CC) SCS

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
1192
KARAMI and KHODABAKHSHI
disadvantages such as unsatisfactory product yields, harsh conditions, long reac-
tions times, and critical product isolation procedures.
In recent years, heterogeneous catalysts have gained importance because of
enviro-economic reasons. They have successfully been utilized in several organic
transformations in order to minimize undesirable wastes which could pollute the
environment.
Recently, the use of magnesium sulfate as an efficient and very cheap re-
20
agent for the preparation of bis(indolyl)methanes was reported.
RESULTS AND DISCUSSION
21
In connection with studies on the synthesis of organic compounds, it was
now found that magnesium sulfate heptahydrate (MgSO ·7H O) can be used as
4
2
an efficient, safe and very cheap catalyst for the condensation of 1,2-dicarbonyl
compounds 1–3 and o-phenylenediamine (4) at room temperature to afford phe-
nazine and quinoxaline derivatives 5–9 in excellent yields (Scheme 1).
Scheme 1. The synthesis of quinoxaline and phenazine derivatives
using MgSO4·7H2O as a catalyst.
In this work, 4,4’-difluorobenzil (1), 9,10-phenanthrenequinone (2) and ace-
naphthoquinone (3) were used as the 1,2-dicarbonyl compounds (Fig. 1).
To determine simple and suitable conditions for the preparation of quino-
xaline and phenazine derivatives using MgSO ·7H O as the Lewis acid catalyst,
4
2
the treatment of 4,4’-difluoro-benzil (1) with o-phenylenediamine (4a) was
chosen as the model reaction (Table I, Entry 5a).
Available online at www.shd.org.rs/JSCS/
_________________________________________________________________________________________________________________________
2011 Copyright (CC) SCS

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
SYNTHESIS OF PHENAZINE AND QUINOXALINE DERIVATIVES
1193
Fig. 1. 1,2-Dicarbonyl compounds.
TABLE I. Synthesis of phenazine and quinoxaline derivatives using 20 mol % MgSO4·7H2O
Entry
5a
Producta
Time, min
30
Yieldb, %
M.p., °C (found (lit.))
F
95
134–136
(135–137)22
N
N
F
F
F
5b
6a
6b
35
15
15
95
90
92
163–165
Me
(165–167)22
N
N
224–226
(223–225)23
N
N
217–219
Me
N
N
(208–210)23
7a
7b
20
20
90
93
237–239
N
(238–240)23
N
N
Me
230–232
(>300)23
N
N
NO2
7c
8
90
50
85
77
320
(>300)24
N
225–227
N
N
N
9
10
98
246–248
O
N
N
a
b
Identified by comparison with authentic samples; refers to isolated yields
It was observed that the condensation reaction can be efficiently realized in
ethanol as solvent by the addition of 20 mol % of the catalyst in a short time span
Available online at www.shd.org.rs/JSCS/
_________________________________________________________________________________________________________________________
2011 Copyright (CC) SCS

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
1194
KARAMI and KHODABAKHSHI
of 30 min. The use of excess amounts of the catalyst did not have a marked in-
fluence on the product yield. The probable reason for this is the coordination of
excessive catalyst to the diamine.
In order to prove the general applicability of this method, after optimizing
the reaction conditions, different 1,2-dicarbonyl compounds were treated with o-
phenylenediamines at room temperature in ethanol. The results are presented in
Table I.
Although the generally mechanistic details of this reaction are not yet fully
understood, a feasible pathway might involve the complexation of magnesium
with the dicarbonyl, thereby acting as a Lewis acid, and also playing a complex
role in promoting the dehydration steps.
In other variations, with the aim of synthesizing products which have not
hitherto been reported, it was found that 1,2-pyridinediamine underwent conden-
sation with compound 2 to produce dibenzo[f,h]pyrido[2,3-b]quinoxaline (8) in
77 % yield (Scheme 2); in a similar way, condensation of 3,4-benzophenone-
diamine with compound 2 produced dibenzo[a,c]phenazine-11-ylphenylmethanone
(9) (Scheme 2).
Scheme 2. Synthesis of new 1,4-benzodiazines using MgSO4·7H2O as a catalyst.
All products were characterized by their spectral and physical data, which,
22–25
when available, were compared with those reported in the literature.
2,3-Bis(4-fluorophenyl)quinoxaline (5a). Yield: 95 %; m.p. 134–136 °C. IR
–1
1
(KBr, cm ): 3061, 1599, 1555, 1511, 1344, 1225, 839, 786. H-NMR (400
MHz, CDC1 , δ / ppm): 7.97 (2H, dd, J = 6.4 Hz, 3.6 Hz), 7.60 (2H, dd, J = 6.4
3
13
Hz, 3.2 Hz), 7.30–7.33 (4H, m), 6.86 (4H, t, J = 8.8 Hz). C-NMR (100 MHz,
Available online at www.shd.org.rs/JSCS/
_________________________________________________________________________________________________________________________
2011 Copyright (CC) SCS