Efficient solvent-free synthesis of pyridopyrazine and quinoxaline derivatives using copper-DiAmSar complex anchored on SBA-15 as a reusable catalyst

Article abstract of DOI:10.1016/S1872-2067(15)60845-2

A catalytic system comprising mesoporous silica functionalized with Cu(II)-DiAmSar was synthesized. This was demonstrated as an efficient heterogeneous catalyst for the synthesis of biologically useful pyridopyrazine and quinoxaline heterocycles under solvent-free conditions. X-ray diffraction, transmission electron microscopy, N₂ adsorption-desorption, Fourtier transformation infrared spectroscopy, and thermogravimetric analysis were used to characterize the catalyst and investigate the texture of SBA-15 during the grafting process.

Full text of DOI:10.1016/S1872-2067(15)60845-2

Chinese Journal of Catalysis 36 (2015) 1379–1386
a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m
j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / c h n j c
Article
Efficient solvent-free synthesis of pyridopyrazine and quinoxaline
derivatives using copper-DiAmSar complex anchored on SBA-15
as a reusable catalyst
Marzieh Mohammadi a, Ghasem Rezanejade Bardajee b,*, Nader Noroozi Pesyan a
a Department of Chemistry, Faculty of Science, Urmia University, 57159, Urmia, Iran
b Department of Chemistry, Payame Noor University, P.O. BOX, 19395-3697, Tehran, Iran
A R T I C L E I N F O
A B S T R A C T
Article history:
A catalytic system comprising mesoporous silica functionalized with Cu(II)-DiAmSar was synthe-
sized. This was demonstrated as an efficient heterogeneous catalyst for the synthesis of biologically
useful pyridopyrazine and quinoxaline heterocycles under solvent-free conditions. X-ray diffraction,
transmission electron microscopy, N2 adsorption-desorption, Fourtier transformation infrared
spectroscopy, and thermogravimetric analysis were used to characterize the catalyst and investi-
gate the texture of SBA-15 during the grafting process.
Received 14 February 2015
Accepted 17 March 2015
Published 20 August 2015
Keywords:
DiAmSar
SBA-15
© 2015, Dalian Institute of Chemical Physics, Chinese Academy of Sciences.
Published by Elsevier B.V. All rights reserved.
Heterogeneous catalyst
Pyridopyrazine
Quinoxaline
1. Introduction
systems consist of a metal and ligands in a particular
stoichiometric ratio, and the removal of the ligands makes the
purification of the product even more expensive. The design
and development of new types of heterogeneous catalysts can
mitigate these problems as it allows the straightforward
removal of the catalyst from the reaction system.
Mesoporous silica has recently gained considerable
attention in organic synthesis under heterogeneous reaction
conditions, but they are not often used as catalysts. The surface
functionalization of mesoporous silica by grafting or co-
condensation is a promising approach for preparing efficient
solid base catalysts. This method provides a way to attach
catalytic centers onto mesoporous silica and avoids metal ion
leaching [6–10]. Various silica supports like the M41S materials
and SBA families with pore sizes between 2 and 50 nm have
received attention in catalysis due to their high surface area (up
Natural and synthetic quinoxalines and their derivatives are
well-known for their biological activities, including antiviral,
antibacterial, anti-inflammatory, antiprotozoal, and kinase
inhibitor behavior [1,2]. There are many pharmaceutical drugs
such as Varenicline 1 (aid in smoking cessation), Brimonidine 2
(antiglaucoma activity), and Quinacillin
3 (antibacterial
properties) that contain quinoxaline cores (Fig. 1) [3–5]. Thus,
there is still a need for the development of a new, convenient,
and environmentally benign synthesis approach.
In recent years, the heterogenization of homogenous
catalysts has attracted attention because this overcomes
several disadvantages such as tedious purification of the
product and undesired wastewater produced in homogeneous
base-catalyzed processes. Furthermore, many homogeneous
* Corresponding author. Tel: +98-28-33336366; Fax: +98-28-33344081; E-mail: rezanejad@pnu.ac.ir
This work was supported by Payame Noor University.
DOI: 10.1016/S1872-2067(15)60845-2 | http://www.sciencedirect.com/science/journal/18722067 | Chin. J. Catal., Vol. 36, No. 8, August 2015

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Marzieh Mohammadi et al. / Chinese Journal of Catalysis 36 (2015) 1379–1386
Fig. 1. Drug products that contain quinoxaline cores.
to 1200 m2/g), uniform and tunable pore size, organic solvent
tolerance, and large diversity in surface functionalization
[11–13]. SBA-15 is the most well-known representative of this
class of materials with good hydrothermal stability, hexagonal
arrays of uniform pores with a high specific surface area,
sufficient silanol groups for surface modification, and large
pore volume that facilitates the grafting of homogeneous metal
compounds through coordinative linkage [14–16].
Nowadays, organic-inorganic hybrids are of great interest
because they combine the advantages of heterogeneous
catalysts (high mechanical, thermal, and structural stability)
and organic molecules (flexibility and functionality) [17,18].
We have focused on the synthesis of some heterogeneous
organometallic catalysts and applied them in organic synthesis
[19–23]. Here we report the application of a novel heteroge-
neous catalyst for the synthesis of biologically active
pyrido[2,3-b]pyrazine and quinoxaline heterocycles under
solvent-free conditions. The procedure for the preparation of
the heterogeneous nanocatalyst is described in Schemes 1 and
Scheme 2. Preparation of Cu(II)-DiAmSar complex anchored on
SBA-15 (Cu(II)-DiAmSar/SBA-15).
2
[24]. The catalyst consists of DiAmSar ligands 7
(3-Chloropropyl)trimethoxysilane reacted with the DiAmSar’s
amine functionality, complexed with the Cu(II) salt and was
covalently immobilized on SBA-15 through the trimethox-
ysilane moiety (Scheme 2).
(hexaminemacrobicyclic cage amine ligands which are known
by their trivial name, sarcophagines, Scheme 1). This not only
forms remarkably stable complexes with transition metal ions
such as Cu(II), but also have fast complexation kinetics even at
a low concentration of metal ions [25,26]. So this catalytic
system has virtually no Cu-leaching. DiAmSar-based ligands are
also appropriate for the encapsulation of radioisotope metal
ions. They can conjugate to peptides, antibodies, and biologi-
cally compatible polymers by their amine functional groups, so
they can be radio-labelled with PET (diagnostic positron emis-
sion tomography) isotopes for the imaging of molecular inter-
actions [27–30].
2. Experimental
2.1. Materials
Acetonitrile, ethanol, formaldehyde, NaOH, methanol, stan-
nous chloride dihydrate, CoCl2·6H2O, sodium cyanide, nitro-
methane, ethylanediamine, commercial 1,2-phenylenedia-
mines, 2,3-diaminopyridine, 3,4-diaminopyridine, 1,2-dicar-
bonyl compounds, poly(ethylene oxide)-block-poly(propylene
oxide)-block-poly(ethylene oxide) triblock copolymer (P123),
(3-chloropropyl)trimethoxysilane (CPTMS), copper (II) acetate
monohydrate, tetraethyl orthosilicate (TEOS), HNO3, and HCl
were purchased from Sigma-Aldrich, Merck, and Acros chemi-
cal companies. Doubly distilled water was used when neces-
sary. All materials were used without further purification. The
solvents used for the synthesis were analytical grade and were
used as received. Silica gel (Merck, grade 9385, 230–400 mesh,
60 Å) for column chromatography was used as received. All
other reagents were purchased from Merck and used as re-
ceived unless otherwise noted. The course of the synthesis of
the heterocycle was followed by TLC on a silica gel plate
(Merck, silica gel 60 F254, ready-use) using methanol (9:1) or
n-hexane:ethyl acetate (1:3) as eluent. The eluent for column
chromatography was the same as the TLC eluent.
To prepare the title heterogeneous catalyst, Cu(II)-DiAmSar
complex was anchored onto the SBA-15 mesoporous material.
Scheme 1. Preparation of DiAmSar.

Marzieh Mohammadi et al. / Chinese Journal of Catalysis 36 (2015) 1379–1386
1381
2.2. Characterization
2.3. General procedure for the synthesis of pyrazine-based
heterocycles under solvent-free conditions
Transmission electron microscopy (TEM) observation was
performed with a Hitachi H-700 CTEM. Fourier transformation
infrared (FT-IR) spectra were recorded using KBr pellets on a
Jasco 4200 FT-IR spectrophotometer. X-ray diffraction (XRD;
Bruker D8ADVANCE with Ni-filtered Cu Kα radiation at 1.5406
Å) was carried out with a speed of 2°/min and a step of 0.05°.
1H and 13C NMR spectra were recorded at room temperature on
Bruker AC 300 and 500 MHz spectrometers using CDCl3 or
DMSO-d6 as the NMR solvent. 1H NMR spectra were referenced
to tetramethylsilane (0.00 ppm), and 13C NMR spectra were
referenced from the solvent central peak (for example, 77.23
ppm for CDCl3). Chemical shifts are given in ppm. N2 adsorp-
tion-desorption isotherms were obtained at –196 °C with a
Quantachrome Autosorb-1 apparatus. Before measurement,
the sample was outgassed at 120 °C for 12 h. The specific sur-
face area and pore size distribution were obtained from the
desorption branch of the isotherm using the BET method and
BJH analysis, respectively. A Shimadzu AA-6300 flame atomic
absorption spectrometer was used to get the concentration of
metal ions. For this purpose, 0.1 g of the catalyst was digested
by HNO3 with stirring at room temperature for a week. Then
the mixture was filtered and the solid was washed several
times with water to get a colourless filtrate solution for metal
measurement. The concentration of Cu(II) in the immobilized
SBA-15 was 0.016 mmol/g. Thermogravimetric analysis (TGA)
was carried out with a TGA/DTA Shimadzu-50 instrument
equipped with a platinum pan. The sample was heated in air
from 25 to 1000 °C with a heating rate of 10 °C/min. The
weight loss was recorded as a function of temperature. Melting
points were recorded using a Buchi B540 melting point appa-
ratus and were uncorrected.
A round-bottomed flask equipped with a magnet and con-
denser was charged with the desired 1,2-diamine (1.0 mmol),
1,2-diketone (1.0 mmol), and catalyst (Cu(II)DiAmSar/SBA-15,
0.005 g). The resulting mixture was heated at 100 °C for the
appropriate time. The course of the reaction was monitored
using TLC on silica gel. Finally, the reaction mixture was cooled,
and the crude mixture was purified by column chromatography
or crystallization to get the desired product. Spectral and phys-
ical data for all heterocycles were compared with reference
samples and were in accord with previously reported data.
Selected spectroscopic data for compounds 10v and 10w
were as follows.
8-Methyl-8,9-dihydro-acenaphtho[1,2-b]pyrazine 10v. Yield
98%; yellow solid, mp: 73–75 °C. IR (KBr) υ (cm–1): 3010, 2929,
1
1680, 1492, 1121. H NMR (300 MHz, CDCl3) δ 1.45 (d, J = 7.1
Hz, 3H), 3.54 (dd, J = 11.1 Hz, 6.0 Hz, 1H), 3.84–3.92 (m, 1H),
4.06 (dd, J = 10.9 Hz, 6.1 Hz, 1H), 7.65 (t, J = 7.5 Hz, 2H),
7.89–7.95 (m, 4H). 13C NMR (75 MHz, CDCl3) δ 158.3, 157.9,
141.6, 131.7, 131.5, 130.6, 128.4, 128.2, 127.8, 118.7, 118.6,
51.8, 49.7, 20.2. Anal. Calcd. for C15H12N2 (220.2): C, 81.79; H,
5.49; N, 12.72. Found: C, 81.68; H, 5.35; N, 12.59.
2-Methyl-dibenzo[f,h]quinoxaline 10w. Yield 80%; white
solid, mp: 121–123 °C. IR (KBr) υ (cm–1): 3018, 2920, 1610,
1501, 1212. 1H NMR (300 MHz, CDCl3) δ 2.84 (s, 1H), 7.71–7.80
(m, 4H), 8.62 (d, J=7.5 Hz, 2H), 8.77 (s, 1H), 9.18 (d, J = 8.1 Hz,
1H), 9.26 (d, J = 7.5 Hz, 1H). 13C NMR (75 MHz, CDCl3) δ: 152.6,
143.8, 140.2, 138.7, 131.4, 130.9, 130.0, 129.9, 129.2, 128.9,
128.4, 127.6, 127.5, 125.3, 124.9, 122.6, 22.2. Anal. Calcd. for
C17H12N2 (244.2): C, 83.58; H, 4.95; N, 11.47. Found: C, 83.65; H,
4.82; N, 11.30.
120
(a)
(b)
100
80
60
40
20
0
1404
(1)
(2)
(1)
(2)
1640
1457
2935
3392
4000 3500 3000 2500 2000 1500 1000
Wavenumber (cm1)
500
0
2
4
6
8
10
2/(o )
(c)
(c)
((dd))
Fig. 2. (a) FT-IR spectra of SBA-15 (1) and Cu(II)-DiAmSar/SBA-15 (2). (b) XRD patterns of SBA-15 (1) and Cu(II)-DiAmSar/SBA-15(2). (c,d) TEM
images of Cu(II)-DiAmSar/SBA-15. (c) in the direction of the pore axis; (d) in the perpendicular direction to the pore axis.

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Marzieh Mohammadi et al. / Chinese Journal of Catalysis 36 (2015) 1379–1386
3. Results and discussion
Table 1
Textural properties of SBA-15 and Cu(II)-DiAmSar/SBA-15.
3.1. Characterization of Cu(II)-DiAmSar complex anchored
onto SBA-15
Material
SBET a (m2/g) VBJH b (cm3/g) DBJH c (nm)
SBA-15
532
317
0.600
0.560
6.24
6.10
Cu(II)-DiAmSar/SBA-15
a Specific surface area.
b Pore volume.
The successful grafting of the Cu(II)-DiAmSar complex onto
SBA-15 was characterized using various physico-chemical
techniques. The FT-IR spectra of SBA-15 and Cu(II)-DiAmSar/
SBA-15 are shown in Fig. 2(a). Cu(II)-DiAmSar/SBA-15 showed
both the silica framework and DiAmSar complex characteristic
bands, including a strong absorbing band at 1000–1200 cm–1
(stretching vibration of the Si–O–Si bond), a broad band
between 3000 and 3600 cm–1 (stretching vibration of NH (from
DiAmSar) and OH (from SBA-15) groups), a peak at 1640 cm–1
(bending of the NH group), a medium band observed at 2955
cm–1 (stretching vibration of CH2), and peaks at 1400–1500
cm–1 (absorption peaks of C–N groups).
c Pore diameter (calculated from the adsorption branch).
cage-like structure of SBA-15 was maintained after grafting
with Cu(II)-DiAmSar [32]. The textural parameters of the
samples are collected in Table 1. As can be seen, the surface
area, pore diameter, and pore volume of Cu(II)-DiAmSar/
SBA-15 decreased with the immobilization of Cu(II)-DiAmSar
inside the channels of SBA-15.
Table 2
Screening of the reaction conditions for the reaction of 1,2-phenylene-
The quality and structural ordering of Cu(II)-DiAmSar/
SBA-15 were determined by XRD. The XRD patterns of both
SBA-15 and Cu(II)-DiAmSar/SBA-15 (Fig. 2(b)) exhibited an
intense peak at 1.1° corresponding to the (100) reflection, and
two low intensity peaks at 1.72° and 1.98° that were indexed as
the (110) and (200) reflections. These peaks are from the
ordered hexagonal unit cell of the mesoporous material and
showed that the structure of mesoporous SBA-15 was retained
during immobilization [31]. Furthermore, the lower angle in
the XRD pattern of Cu(II)-DiAmSar/SBA-15 was due to the
development of a unit cell arising from the connection of the
complex in SBA-15, and the lower intensity was due to a de-
crease in the mesoscopic order.
The TEM images of Cu(II)-DiAmSar/SBA-15 are presented
in Fig. 2(c) and (d) in the direction of the pore axis (Fig. 2(c))
and perpendicular to the pore axis of Cu(II)-DiAmSar/SBA-15
(Fig. 2(d)). The TEM images of the supported complex
confirmed the retaining of the cylindrical shape of the pores
and the hexagonal arrays of uniform channels.
diamine 8a and benzil 9a.
Catalyst
(10–5 mmol)
Time
(min)
320
10
10
10
10
10
120
100
80
Yield a
(%)
—
30
30
20
65
99 (98c)
80
Entry Solvent
t/°C
1
2
Free
Free
0
8
16
0.8
8
rt
rt
rt
rt
60
100
Reflux
Reflux
100
Reflux
3
Free
4
Free
5
Free
6b
Free
8
8
7
H2O
8
9
10
EtOH
DMF
Toluene
8
8
8
85
78
85
160
Reaction conditions: 1,2-Phenylenediamine 8a (1 mmol, 1 equiv), ben-
zil 9a (1.0 mmol, 1 equiv) and catalyst (0–0.00016 mmol based on
Cu(II) ions or 0–0.05 g of Cu(II)-DiAmSar/SBA-15) were heated for an
appropriate time in a solvent (2 mL) or solvent-free conditions.
a Based on GC yields.
b Optimum conditions.
c Isolated yield.
N2 adsorption-desorption isotherms and pore size
distributions of the samples are depicted in Fig. 3(a). Both
SBA-15 and Cu(II)-DiAmSar/SBA-15 exhibited type IV
isotherms with a small H1 hysteresis loop, showing that the
500
1000
800
600
400
200
0
(a)
(b)
100
80
60
40
20
0
(1)
(2)
(1)
(2)
(1)
(3)
400
300
200
100
0
0 1 2 3 4 5 6 7 8 910
rp/nm
(2)
0.0
0.2
0.4
0.6
0.8
1.0
0
100 200 300 400 500 600 700 800 900
Temperature (oC)
Relative pressure (p/p0)
Fig. 3. (a) N2 adsorption isotherms and corresponding pore size distributions (inset) of SBA-15 (1) and Cu(II)-DiAmSar/SBA-15(2). (b) TGA curves of
SBA-15(1), Cu(II)-DiAmSar/SBA-15(2), and DiAmSar (3).

Marzieh Mohammadi et al. / Chinese Journal of Catalysis 36 (2015) 1379–1386
1383
Figure 3(b) illustrates the TGA profiles of pure SBA-15 and
Cu(II)-DiAmSar/SBA-15. Pure siliceous SBA-15 showed a mass
loss below 100 °C due to the loss of physically adsorbed water
from the surface of SBA-15. The thermogram of Cu(II)-DiAm-
Sar/SBA-15 showed weight losses at two temperatures: the
weight loss at 100 °C was from dehydration and the weight loss
between 200 and 700 °C was from the thermal decomposition
of grafted Cu(II)-DiAmSar moieties. These results confirmed
the successful grafting of the Cu(II)-DiAmSar complex on the
SBA-15 surface. According to the TGA data, the grafting amount
of DiAmSar on SBA-15 was 62 wt% (based on the initial
amount of DiAmSar used for the anchoring).
3.2. Catalyst activity
To test the activity of the catalyst, initially, the reaction
between 1,2-phenylenediamine (8a) and benzil (9a) was
selected as a model reaction to find the best reaction conditions
(Table 2). In the first attempt, we examined the reaction at
room temperature in the absence of the catalyst, which gave no
Table 3
Synthesis of 2,3-disubstituted quinoxalines catalyzed by Cu(II)-DiAmSar/SBA-15.
m.p. (°C) (lit.)
Entry
Diamine 8
Diketone 9
Product 10
Yield (%) Time (min)
NH2
N
N
O
1
98
92
99
10
10
5
121–123 (124 [33])
O
NH2
8a
9a
10a
OMe
OMe
O
O
N
N
2
3
8a
148–150 (151–152.5 [33])
133–134 (135–137 [33])
OMe
F
OMe
F
10b
9b
9c
N
N
O
8a
8a
O
F
F
10c
N
O
O
Me
Me
Me
4
5
99
88
5
102–104 (104–106 [34])
183–185 (183 [34])
N
10d
Me
9d
O2N
NH2
O2N
N
N
30
9a
NH2
8b
8b
10e
10f
10g
O2N
N
Me
6
7
9d
9a
99
99
5
5
130–132 (131–133 [35])
114–116 (110–111 [35])
N
N
Me
Ph
Me
Me
NH2
NH2
N
Ph
8c
8c
OMe
Me
N
8
9
96
99
20
5
123–125 (124–126 [35])
90–92 (92–94 [35])
9b
9d
N
OMe
10h
Me
N
N
Me
Me
8c
10i
Reaction conditions: 1,2-Phenylenediamine 8a (1 mmol, 1 equiv), benzil 9a (1.0 mmol, 1 equiv) and catalyst (0.005 g of Cu(II)-DiAmSar/SBA-15 or
8  10–5 mmol based on Cu(II) ions) were heated at 100 °C under solvent-free conditions.

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Marzieh Mohammadi et al. / Chinese Journal of Catalysis 36 (2015) 1379–1386
yield of product. Although using dimethylformamide and
ethanol as solvent gave reasonable yields (Table 2, entries 8
and 9), the best yield was obtained under the solvent-free
condition at 100 °C and in the presence of 8 × 10–5 mmol of the
catalyst (Table 2, entry 6).
With the optimized conditions in hand, the generality of the
reaction was evaluated by using various diamines and
1,2-diketones (Tables 3 and 4). Most of the substrates gave
good to excellent yields in short reaction times.
The reactivity of aromatic and hetero-aromatic diamines is
generally dominated by electronic effects. In general, aromatic
and hetero-aromatic diamines with electron-withdrawing
groups (EWG) react more slowly when compared to other
diamines. For example, the condensation reaction of less
phenylenediamines bearing EWG (Table 3, entry 5) and
diaminopyridines (Table 4, entries 1–9), was slower and gave
lower yields. The reactivity of the aliphatic diamines with
various 1,2-diketones was good (Table 4, entries 10–12 and
14). New quinoxaline derivatives were synthesized through the
reactions of aliphatic diamine (1,2-diaminopropanean 8h) with
acenaphthenequinone 9e and phenanthrenequinone 9f (Table
4, entries 13 and 14) in high yields and at lower temperature
than the optimized conditions. The initial products of the
aliphatic diamines can undergo a further oxidation step to give
fully aromatic and stable final products (Table 4, entries 10, 11,
and 13). For example, the reaction of aliphatic diamine 8h and
diketone 9f (Table 4, entry 14) gave directly the final product
10w (fully aromatic) via a one-pot protocol. The presence of a
singlet peak at 2.84 ppm for the CH3 group and another singlet
electron-rich
diamines,
including
substituted
1,2-
Table 4
Synthesis of pyridopyrazine and pyrazine derivatives in the presence of a catalytic amount of Cu(II)-DiAmSar/SBA-15.
En- Diamine
Diketone
Yield Time m.p. (°C) En- Diamine Diketone
Yield Time m.p. (°C)
(%) (min) (lit.)
Product 10
Product 10
try
1
8
9
(%) (min)
(lit.)
try
8
9
NH2
NH2
N
Ph
N
N
O
O
141–143
80 45 (142–143
[35])
217–218
80 50 (216–218
[20])
N
9a
9c
9b
8
8e
N
N
N
Ph
8d
8d
10j
10q
9f
10q
F
N
N
N
142–144
85 45 (140–142
[20])
246–248
80 50 (245–247
[20])
N
2
3
9
8e
9e
N
N
10k
F
10r
10k
OMe
NH2
N
N
137–139
154–156
8d
8d
77 90 (139–140 10
[35])
9a
99
5
(160–161
[34])
N
N
N
NH2
10s
10s
10l
OMe
8f
10i
O
N
N
222–224
88 60 (225–227 11
[20])
162–164
(165–167
[20])
O
4
5
8f
9e
9d
99
95
5
5
N
N
N
10t
9e
9b
10m
10t
OMe
NC
NC
NH2
NH2
NH2
NC
N
Me
N
N
145–147
74 90 (147–148 12
[37])
160–162
(162–164
[20])
N
N
NH2
NC
N
Me
10u
8e
8e
10n
8g
OMe
F
10n
NH2
N
N
N
133–135
78 50 (132–134 13
[20])
N
6
7
9c
9a
9e
9f
98
81
5
5
73–75
N
NH2
8h
10o
F
10v
10o
N
N
N
170–172
(173–174
[36])
N
8e
79 60
14
8h
121–123
N
10p
10p
10w
Reaction conditions: 1,2-Phenylenediamine 8a (1 mmol, 1 equiv), benzil 9a (1.0 mmol, 1 equiv) and catalyst (0.005 g of Cu(II)-DiAmSar/SBA-15 or
8  10–5 mmol based on Cu(II) ions) were heated at 100 °C under solvent-free conditions.

Marzieh Mohammadi et al. / Chinese Journal of Catalysis 36 (2015) 1379–1386
1385
peak at 8.77 ppm for the CH group (in pyrazine ring, compound
10w) in the H NMR spectrum demonstrated the synthesis of
Table 5
Reuse of the catalyst for the synthesis of 2,3-diphenylquinoxaline 10a.
1
this derivative. To get more details about the intermediate, we
investigated the corresponding reaction for compound 10w
(unoxidized compound). The reaction was quenched at half its
completion time, and the 1H NMR of the crude mixture was
analyzed (Fig. 4).
Run
1
99
2
99
3
99
4
98
5
97
6
97
7
96
Isolated yield (%)
Table 6
Comparison of our results with some previously reported data for the
synthesis of compound 10a.
The appearance of a doublet peak at 1.46 ppm for CH3 (peak
b) and CH2 diastereotopic hydrogen peaks (d and e peaks) at
3.31 and 3.99 ppm (Fig. 4, compound 10x) demonstrated the
presence of an unoxidized intermediate (compound 10x) in the
reaction mixture. Although products obtained from aliphatic
diamines can be fully aromatic compounds, this was not a
general rule in our protocol. For instance, compound 10v
(Table 4, entry 13) was not oxidized during the reaction. This
was demonstrated by the presence of the doublet peaks of CH2
(diastereotopic hydrogen) at 3.54 and 4.05 ppm, multiplet
peaks of CH hydrogen atom (the H on the carbon chiral center)
at 3.88 ppm, and doublet peaks of the CH3 hydrogen group at
1.46 ppm in 1H NMR spectrum (compound 10v).
Time Yield
(min) (%)
Method
Solvent
t/°C
Ref.
Zr(DS)4
MnCl2
H2O
EtOH
H2O
HFIP
H2O
EtOH
MeOH
MeOH
Water
Solvent-
free
rt
rt
100
rt
rt
rt
30
17
30
60
150
15
5
30
120
5
94 [37]
94 [38]
99 [20]
95 [39]
100 [40]
98 [41]
100 [42]
85 [43]
99 [22]
99 This
work
Pd(II)-Schiff base/SBA-15
—
Mont K-10 (10 mol%)
Silica sulfuric acid
Sulfamic acid
In (5 nmol)/InCl3
Fe(III)-Schiff base/SBA-15
Cu(II)-DiAmSar/SBA-15
25
Reflux
Reflux
100
Some of the reactions in Table 3 were fast enough that they
were completed in shorter reaction times than that of the
optimized conditions. Furthermore, the reactivity of 1,2-
diketones with electron-donating groups was slower with
different diamines, for both the time and yield of the reactions
(Table 4, entries 3 and 5).
The reusability of the catalyst was examined by repeating
the model reaction (compound 10a) under the optimized
conditions. After the first reaction with 98% yield, the catalyst
was first filtered, then washed with hot ethanol, and dried at 80
°C for 60 min. The recovered catalyst was used in another
reaction, and we found that the Cu(II)-DiAmSar/SBA-15
catalyst can be recycled up to six times without any loss of
activity (Table 5).
We compared some previously reported data for the
synthesis of 10a (Table 3, entry 1) with our protocol (Table 6).
Our results were good in comparison to previously reported
data in terms of yields, environment, and reaction times.
4. Conclusions
We synthesized and characterized a new active heteroge-
neous mesoporous catalyst of Cu(II)-DiAmSar complex grafted
onto SBA-15. The catalyst was active for the synthesis of nitro-
gen containing pyrazine-based heterocycles, including pyra-
zine, pyrido[2,3-b]pyrazine, and quinoxaline derivatives, with
good to excellent yields under mild conditions.
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Fig. 4. 1H NMR spectrum of a sample from the crude reaction mixture
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1386
Marzieh Mohammadi et al. / Chinese Journal of Catalysis 36 (2015) 1379–1386
Graphical Abstract
Chin. J. Catal., 2015, 36: 1379–1386 doi: 10.1016/S1872-2067(15)60845-2
Efficient solvent-free synthesis of pyridopyrazine and quinoxaline derivatives using copper-DiAmSar complex anchored on
SBA-15 as a reusable catalyst
Marzieh Mohammadi, Ghasem Rezanejade Bardajee*, Nader Noroozi Pesyan
Urmia University, Iran; Payame Noor University, Iran
SBA-15
HN
NH
H
N
Cu (II)
NH2
HN
HN
NH
NH
N
N
R
R
NH2
NH2
O
O
R
R
Cu(II)-DiAmSar/SBA-15
Solvent-free, heat
+
Y
Y
X
X
21 examples
80% 100%
X and Y = C or N
R = Aliphatic or Aromatic
A silica-based mesoporous organic–inorganic hybrid catalyst was synthesized by anchoring Cu(II)-DiAmSar on SBA-15, which gave high
activity for the synthesise of pyridopyrazine and quinoxaline derivatives under solvent-free conditions.
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