A recyclable and highly effective sulfated TiO2-P25 for the synthesis of quinoxaline and dipyridophenazine derivatives at room temperature

Article abstract of DOI:10.1016/j.jorganchem.2010.08.055

Sulfated TiO₂-P25 has been prepared using H₂SO ₄ and used for the synthesis of quinoxaline and dipyridophenazine derivatives. Sulfate loading by H₂SO₄ increases the Lewis acidity of TiO₂-P2

Full text of DOI:10.1016/j.jorganchem.2010.08.055

Journal of Organometallic Chemistry 695 (2010) 2572e2577
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Journal of Organometallic Chemistry
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Communication
A recyclable and highly effective sulfated TiO2-P25 for the synthesis
of quinoxaline and dipyridophenazine derivatives at room temperature
*
B. Krishnakumar, M. Swaminathan
Department of Chemistry, Annamalai University, Annamalainagar 608 002, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Sulfated TiO2-P25 has been prepared using H2SO4 and used for the synthesis of quinoxaline and
dipyridophenazine derivatives. Sulfate loading by H2SO4 increases the Lewis acidity of TiO2-P25. This
catalyst gives excellent yield with less reaction time and it is an inexpensive, easily recyclable catalyst for
this reaction.
Received 7 July 2010
Received in revised form
26 August 2010
Accepted 31 August 2010
Available online 6 September 2010
Ó 2010 Elsevier B.V. All rights reserved.
Keywords:
Sulfated TiO2-P25
Quinoxaline
Dipyridophenazine
Green synthesis
1. Introduction
respectively. This reveals that TiO2-P25-SO24ꢀ has more acidic sites
when compared to bare TiO2-P25.
Catalysis is one of the fundamental pillars of green chemistry.
The design of chemical products and processes that reduce or
eliminate the use and generation of hazardous substances has lead
to the design and application of catalysts and catalytic systems to
achieve the dual goals of environmental protection and economic
benefit [1]. Degussa TiO2-P25 (80% anatase, 20% rutile) is a well
known and widely investigated photocatalyst. Acidebase and
redox properties are one of the most important types of surface
chemical properties of metal oxide catalysts. From a catalytic point
of view, transition metal oxide TiO2 possesses a unique type of
surface involving both redox and acidebase sites. In addition to
high thermal stability, its amphoteric character makes titania
a promising catalytic material. The textural and acidebase prop-
erties of titania depend greatly on method of preparation. Doping of
sulfate using H2SO4 makes the catalyst more acidic [2] when
compared to TiO2-P25. Since the surface of TiO2-P25-SO24ꢀ is posi-
tively charged due to protonation as shown in Scheme 1 it acts as
a strong Lewis acid. Surface acidity was determined by the spec-
trophotometric method on the basis of irreversible adsorption of
organic base pyridine [3e5]. The amount of pyridine adsorbed by
Quinoxaline derivatives are the subject of considerable interest
from both academic and industrial perspectives because they are
significant intermediates for the manufacturing of pharmaceuticals
and advanced materials [6,7]. They have been shown to possess
a broad spectrum of biological activities such as antiviral, antibac-
terial, anti-inflammatory, antitumor and antidepressant activities
[8e10]. Dipyridophenazines were used as a metal ligand for the
formation of metal-ligand complexes with attractive features [11].
A number of synthetic strategies have been developed for the
preparation of substituted quinoxalines and dipyridophenazines
[11e13]. The most common method is the condensation of an aryl-
1,2-diamine with a 1,2-dicarbonyl compound in refluxing ethanol
or acetic acid [14].
Lewis acids and many other catalysts including sulfamic acid
[15], montmorillonite K-10 [16], polyaniline-sulfate salt [17],
H6P2W18O62,24H2O [3], InCl3 [18], CuSO4,5H2O [19] have been
explored. There are a few constraints like the use of strong acids
and high reaction temperatures. Recent research has been focused
on finding new catalysts to improve the yield of this condensation
reaction.
Jing Cai et al. [20] reported the synthesis of quinoxaline deriva-
tives using gallium(III) triflate in good yield and less reaction time.
But this catalyst is acidic, hygroscopic and hazardous in nature.
Ahmad shaabani et al. [21,22] reported two solid acid catalyst cellu-
lose sulfuric acid (CSA) and silica sulfuric acid (SSA) for this synthesis.
Though they give good yield with reusability, preparation of these
0.1
g
of TiO2-P25 and TiO2-P25-SO24ꢀ are 40 and 170
mg,
* Corresponding author. Tel.: þ91 4144 225072.
E-mail address: chemres50@gmail.com (M. Swaminathan).
0022-328X/$ e see front matter Ó 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2010.08.055

B. Krishnakumar, M. Swaminathan / Journal of Organometallic Chemistry 695 (2010) 2572e2577
2573
Scheme 1. Protonation of TiO2-P25-SO42ꢀ
.
Scheme 2. The condensation reaction of 1,2-phenylenediamine 1a with benzil 2a catalyzed by TiO2-P25-SO42ꢀ
.
catalysts involves the evolution of HCl. As the aforesaid methods are
not compatible with heat or acid sensitive substrates, there is a need
to develop an effective synthesis of quinoxalines employing more
eco-friendly catalysts. Our laboratory has been engaged mainly on
the development of modified semiconductor photocatalysts for
environmental remediation and organic synthesis [5,23e25] Herein,
we report the preparation of a recyclable, easily separable, eco-
friendly and highly effective solid acid catalyst TiO2-P25-SO24ꢀ for the
green synthesis of quinoxaline and dipyridophenazine derivatives at
room temperature.
increased to 7 wt.%, the product yield decreased to 95.8% (Table 1,
entry 6). Hence 5 wt.% of sulfate was found to be the optimum level.
The reaction between 1,2-phenylenediamine and benzil was
carried out in the solvents acetonitrile, water and 95% ethanol in
water under the same reaction conditions. In the solvents aceto-
nitrile and ethanol the reaction could be completed in 5 min with
a quantitative yields of product 95.7 and 98.0%, respectively (Table
1, entries 3, 2). It was found that reaction in water required a longer
time (15 min) to give 90.4% (Table 1, entry 4) yield of product.
Because of high product yield with less reaction time and easy
availability, 95% ethanol was chosen as a solvent for further
reactions.
2. Results and discussion
2.1. Effect of different catalysts and solvents
2.2. Effect of catalyst loading
In order to optimize the condensation reaction conditions such
as percentage of sulfate in the catalyst and also to check the
versatility of this method with substituted 1,2-phenylenediamines,
the reaction was carried out under various conditions. The
condensation reaction of 1,2-phenylenediamine 1a and benzil 2a
(Scheme 2) was carried out in the presence of TiO2-P25 and TiO2-
P25-SO24ꢀ with different concentrations of sulfate at room
temperature for 5 min in ethanol medium. The yield with TiO2-P25
was found to be 91.8% (Table 1, entry 1). It was surprising to find
that the reaction with TiO2-P25-SO24ꢀ could be completed in 5 min
to give quantitative yield of 98.0% of product quinoxaline 3a (Table
1, entry 2). Structure of this product has been confirmed by spectral
and GCeMS data. The percentage yield of the product with 3 and
5 wt.% of sulfate concentrations are 94.5 and 98.0%, respectively
(Table 1, entries 5, 2). The same reaction when performed without
catalyst for 3 h gave no product. When the sulfate content was
The effect of catalyst loading on the formation of quinoxaline
was investigated by varying the catalyst amount from 0.05 to 0.2 g
(Fig. 1). Increase in catalyst amount from 0.05 to 0.1 g increases the
formation of quinoxaline from 92.5 to 98.0%. This is due to increase
in the number of TiO2-P25-SO24ꢀ particles. Above 0.1 g of the
catalyst, no significant change in the conversion occurred. The
Table 1
Effect of different solvent and catalyst (0.1 g) on condensation of o-phenylenedi-
amine (1 mmol) and benzil (1 mmol) under room temperature.
Entry
Catalyst
Solvent
Yielda (%)
1
2
3
4
5
6
TiO2-P25
95% ethanol (5)
95% ethanol (5)
(CH3CN (5)
(H2O) (15)
95% ethanol (5)
95% ethanol(5)
91.8
98.0
95.7
90.4
94.5
95.8
5 wt.% of TiO2-P25-SO42ꢀ
5 wt.% of TiO2-P25-SO42ꢀ
5 wt.% of TiO2-P25-SO42ꢀ
3 wt.% of TiO2-P25-SO42ꢀ
7 wt.% of TiO2-P25-SO42ꢀ
Values within parentheses are indicating reaction time in min.
Fig. 1. Effect of catalyst loading: o-phenylenediamine ¼ 1 mmol, benzil ¼ 1 mmol,
solvent ¼ 95% ethanol in water (5 mL), time ¼ 5 min (stirring at room temperature).
a
Yields with respect to 1,2-diamine.

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B. Krishnakumar, M. Swaminathan / Journal of Organometallic Chemistry 695 (2010) 2572e2577
Table 2
Quinoxaline derivatives from different 1,2-diamines and 1,2-diketone (benzil) catalyzed by TiO2-P25-SO42ꢀ
.
Entry
1
1,2-Diamine
1,2-Diketone
Product
Time (min)
5
Yielda (%)
98.0
NH2
O
N
N
NH2
1a
O
3a
2a
2a
2a
2a
2a
2a
2a
2
3
4
5
6
7
45
120
120
120
60
97.6
95.5
93.0
60.0
78.0
80.5
NH2
O
O
N
H3C
NH2
1b
H3C
N
3b
NH2
O
O
N
F
NH2
1c
F
N
3c
NH2
NH2
O
O
N
Cl
1d
Cl
N
3d
HOOC
NH2
O
O
HOOC
N
NH2
1e
N
3e
NH2
O
O
N
N
N
NH2
1f
N
3f
60
NH2
O
O
N
N
NH2
1g
3g
a
Yields with respect to 1,2-diamine.

B. Krishnakumar, M. Swaminathan / Journal of Organometallic Chemistry 695 (2010) 2572e2577
2575
Table 3
Dipyridophenazine derivatives from different 1,2-diamines and 1,2-diketone (1,10-phenanthroline-5,6-dione) catalyzed by TiO2-P25-SO42ꢀ
.
Entry
1
1,2-Diamine
1,2-Diketone
Product
Time (min)
4
Yielda (%)
99.0
NH2
O
O
N
N
N
NH2
1a
N
N
N
2b
4a
2
30
98.5
NH2
O
N
O
N
O
N
O
N
CH3
N
N
N
H3C
NH2
1b
N
2b
2b
2b
4b
3
60
96.0
NH2
F
N
N
F
NH2
1c
N
N
4c
4
60
94.9
NH2
NH2
O
N
O
N
O
Cl
N
N
N
Cl
1d
N
4d
5
6
7
60
60
60
65.0
78.5
85.2
HOOC
NH2
O
N
O
N
O
N
N
N
N
NH2
1e
COOH
N
N
O
2b
2b
2b
4e
NH2
N
N
N
N
NH2
1f
N
N
N
O
N
4f
NH2
N
N
N
N
NH2
1g
4g
a
Yields with respect to 1,2-diamine.

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B. Krishnakumar, M. Swaminathan / Journal of Organometallic Chemistry 695 (2010) 2572e2577
Scheme 3. The condensation reaction of 1,2-phenylenediamine 1a with 1,10-phenanthroline-5,6-dione 2b catalyzed by TiO2-P25-SO42ꢀ
.
Scheme 4. Proposed mechanism for the condensation reaction of 1,2-diamine with 1,2-dicarbonyl compounds catalyzed by TiO2-P25-SO42ꢀ
.
optimum catalyst loading is found to be 0.1 g for the formation of
quinoxaline.
with the diketone by acting as an acid and also playing a complex
role in promoting the dehydration. As seen earlier by pyridine
adsorption, the surface acidity of TiO2-P25-SO24ꢀ is much higher
than TiO2-P25. A similar mechanism has been proposed for this
reaction with the catalyst montmorillonite K-10 [16]. The possi-
bility of recycling the catalyst (TiO2-P25-SO24ꢀ) was examined for
the reaction of o-phenylenediamine 1a and benzil 2b. When the
reaction was complete, ethyl acetate was added to the solidified
mixture and the insoluble catalyst was separated by filtration.
The separated catalyst could be used five times without any
treatment and, no appreciable loss in its catalytic activity was
observed up to fifth run (95.3% - Table 4, entry 3). Efficiency of
this solid acid catalyst, TiO2-P25-SO24ꢀ, in the synthesis of qui-
noxaline from o-phenylenediamine and benzyl is compared with
the efficiencies of two solid acid catalysts cellulose sulfuric acid
(CSA) and silica sulfuric acid (SSA) reported for the same reaction
[21,22]. Table 4 gives the product yield in EtOH and H2O for each
catalyst and its reusability in EtOH. Among the three catalysts
2.3. Effect of different substrates
Encouraged by the remarkable results obtained with the above
reaction conditions and in order to show the generality and scope of
this new protocol, we used various substituted 1,2-phenylenedi-
aminesand the results obtainedare summarizedinTables 2 and 3. To
check the versatility of this method, we had also studied the
condensation of 1,2-phenylenediamine with 1,10-phenanthroline-
5,6-dione 2b (Scheme 3) under the same conditions used for qui-
noxalines and the product dipyrido[3,2-a:20,30-c]phenazine 4a
(Table 3) was obtained in excellent yield (99%) within 4 min.
Structure of this product was confirmed by spectral and GCeMS
data. All the reactions with substituted 1,2-phenylenediamines
proceeded very cleanly at room temperature and no undesirable
side-reactions were observed, although the yields were highly
dependent on the substituents. Results in Tables 2 and 3 show that
electron-donating groups at the phenyl ring of 1,2-diamine favored
the formation of product (Table 2, entry 2; Table 3, entry 2). In
contrast, electron withdrawing groups such as fluoro, chloro and
carboxylic slightly lower the yields (Table 2, entries 3e5; Table 3,
entries 3e5) with longer reaction times. 2,3-diaminopydrine and
aliphatic diamine (ethylene diamine) also gave moderate yields
(Table 2, entries 6, 7; Table 3, entries 6, 7).
Table 4
Comparison of catalytic efficiencies for the condensation of o-phenylenediamine
and benzyl at room temperature.
Entry
1
Catalyst
EtOH (time/
Yield (%)a)
H2O (time/
Yield (%)a)
Reference
[21]
Cellulose
sulfuric
60 min/93 (92, 95,
90, 90)b
2.30 h/72
acid (CSA)
Silica sulfuric
acid (SSA)
Sulfated
2
3
15 min/98 (94, 90,
85, 78)b
e
[22]
2.4. Mechanism of the reaction
5 min/98(98, 97.9,
15 min/90.4
Present work
TiO2-P25
96.5, 95.3)b
This reaction is likely to follow the proposed mechanism of
acid-catalyzed condensation reactions as shown in Scheme 4.
This mechanism involves the complexation of TiO2-P25-SO42ꢀ
a
Yield with respect to 1,2-diamine.
The same catalyst was used for each of the five runs.
b

B. Krishnakumar, M. Swaminathan / Journal of Organometallic Chemistry 695 (2010) 2572e2577
2577
TiO2-P25-SO24ꢀ is more efficient as it gives 98% yield in 95%
ethanol-water (5 min) and 90.4% in water (15 min). Even in fifth
run the yield is 95.3% (5 min) which is higher than the yield with
CSA (90% in 60 min) and SSA (78% in 15 min).
are observed at 128.30,128.83,129.05,129.23,129.87,129.99,134.90,
139.10, 141.24 and 153.49 (C]N); GCeMS (m/z) ¼ 283.2 (Mþ1).
4.2.2. Dipyrido[3,2-a:20,30-c]phenazine, 4a
m.p. ¼ 246e247 ꢁC; IR (KBr) (cmꢀ1) ¼ 3073, 2852, 1577, 1498,
3. Conclusions
1415, 1361, 1337, 739, 669; 1H NMR (CDCl3, 300 MHz)
d
¼ 9.65 (2d,
2H), 9.27 (d, 2H), 8.36 (t, 2H), 7.94 (q, 2H), 7.82 (q, 2H); 13C NMR
(CDCl3, 300 MHz)
In conclusion, TiO2-P25-SO24ꢀ is introduced as an excellent solid
acid catalyst for the synthesis of quinoxaline and dipyr-
idophenazine derivatives at room temperature. In comparison with
the previously reported methods, this novel and practical method
has the advantages of mild conditions, quantitative yields of
products, and very short reaction time at room temperature.
Another attractive feature of this green process is its application in
industrial processes due to simple preparation and reusability of
TiO2-P25-SO24ꢀ. Water (green solvent) can also be used as a solvent.
d
¼ aromatic carbons are observed at 124.17,
127.62, 129.56, 130.69, 133.81, 141.14, 142.51, 148.40 (C]N of pyri-
dine ring) and 152.53 (C]N of phenazine ring); GCeMS
(m/z) ¼ 282.9 (Mþ1).
Acknowledgements
One of the authors B. Krishnakumar is thankful to CSIR, New
Delhi, for the award of Senior Research Fellowship. The authors
thank the Ministry of Environment and Forests (MOEF), New Delhi,
for the financial support through research grant No. 315-F-36, F.
No.19/9/2007-RE.
4. Experimental
4.1. Preparation of sulfate loaded TiO2-P25 photocatalysts
About 2.7 g of TiO2-P25 [It is a mixture of 80% anatase and 20%
References
rutile. It has a particle size of 30 nm and BET specific area 50 m2 gꢀ1
]
suspended in 100 ml of 2-propanol and to this solution 3.2 ml of
1 M H2SO4 was added dropwise under vigorous stirring. The
resulting colloidal suspension was stirred for 4 h. The gel obtained
was filtered, washed and dried in an air oven at 100 ꢁC for 12 h.
Addition of BaCl2 to filtrate gave no precipitate indicating that all
the sulfate ions were completely loaded on the gel. This catalyst
contained 5 wt.% of SO24ꢀ. Similarly catalysts with 3 and 7 wt.% of
SO24ꢀ were prepared with the same procedure.
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4.2. Preparation of quinoxaline and dipyridophenazine derivatives e
General procedure
To a mixture of an o-phenylenediamine (1 mmol, 0.108 g) and 1,
2-dicarbonyl compound (1 mmol, 0.210 g) in ethanol (5 mL), 0.1 g of
TiO2-P25-SO24ꢀ was added and the mixture was stirred at room
temperature. The progress of the reaction was monitored by TLC.
After completion of the reaction, ethyl acetate was added to the
solidified mixture and the insoluble catalyst was separated by filtra-
tion. The filtrate was dried over anhydrous Na2SO4. The solvent was
evaporated and the pure product was obtained. Then it was subjected
to GC and GCeMS analysis for the determination of the yield of the
products. The structure of products obtained had been confirmed by
FT-IR,1H NMR,13C NMR and GCeMS analysis. A variety of substituted
1,2-phenylenediamines were condensed with benzil and 1,10-phe-
nanthroline-5,6-dione. The catalyst separated can be reused.
4.2.1. 2,3-Diphenylquinoxaline, 3a
m.p. ¼125e126 ꢁC; IR (KBr) (cmꢀ1) ¼ 3055, 2921,1542,1344, 768,
696; 1H NMR(CDCl3, 300MHz)
d
¼8.19 (dd, 2H), 7.76 (dd, 2H), 7.5 (m,
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172 (2009) 914.
4H), 7.34 (m, 6H); 13C NMR (CDCl3, 300 MHz)
d
¼ aromatic carbons