Copper nanoparticle-doped silica cuprous sulfate as a highly efficient and reusable heterogeneous catalysis for N-arylation of nucleobases and N-heterocyclic compounds

Article abstract of DOI:10.1055/s-0030-1260236

A facile and simple protocol for Ullmann-type N-arylation of nucleobases with aryl halides is described using copper nanoparticle-doped silica cuprous sulfate (CN-DSCS) as a new and efficient heterogeneous catalysis. In this method, treatment of various n

Full text of DOI:10.1055/s-0030-1260236

PAPER
3915
Copper Nanoparticle-Doped Silica Cuprous Sulfate as a Highly Efficient and
Reusable Heterogeneous Catalysis for N-Arylation of Nucleobases and
N-Heterocyclic Compounds
?
?Nano
C
opper??-Dop
o
e
d
Silica Cu
h
prous Sulfateammad Navid Soltani Rad,*a Somayeh Behrouz,*a Mohammad Mahdi Doroodmand,b,c Noushin Moghtaderia
a
b
c
Department of Chemistry, College of Sciences, Shiraz University, Shiraz 71454, Iran
Nanotechnology Research Institute, Shiraz University, Shiraz, Iran
Received 28 July 2011; revised 17 August 2011
This paper is dedicated to Professor Gholam Hossein Hakimelahi who devotes himself to the progress of medicinal chemistry in Iran.
area, excellent stability (chemical and thermal), good ac-
Abstract: A facile and simple protocol for Ullmann-type N-aryla-
cessibility, and the environmental compatibility. Addi-
tion of nucleobases with aryl halides is described using copper
tionally, the organic functionalities can be robustly
nanoparticle-doped silica cuprous sulfate (CN-DSCS) as a new and
efficient heterogeneous catalysis. In this method, treatment of vari-
anchored to the surface of silica gel to provide the appro-
ous nucleobases and aryl halides in the presence of DBU and CN- priate catalytic centers.13,14 The modified silica gels hav-
DSCS in refluxing DMF furnishes the corresponding N-aryl ad-
ing NH2, SH, diamines, and amino acids groups have
ducts in reasonable to good yields. The CN-DSCS was fully charac-
shown to be the suitable supports for bonding with various
terized by different microscopic, spectroscopic and physical
transition metals like Pd, Cu, Sc, Ru, Pt, V, etc. useful in
techniques, including scanning electron microscopy (SEM), trans-
many organic synthesis.15
mission electron microscopy (TEM), atomic force microscopy
(AFM), X-ray diffraction (XRD), inductively coupled plasma (ICP)
The ability to construct N-arylated N-heterocycles is cur-
analysis, thermogravimetric analysis (TGA), and FT-IR. The CN-
rently an active area in organic synthesis due to their prev-
DSCS was proved to be a chemically and thermally stable, cheap,
alence in many natural products and pharmaceutically
and environmentally compatible heterogeneous nanocatalyst that
promising compounds.16 Among them, N-aryl nucleo-
can be reused for many consecutive experiments without any con-
bases have been paid the considerable attention as thera-
siderable decrease in its reactivity.
peutics, molecular tools, and probes for investigating the
Key words: CN-DSCS, heterogeneous catalysis, Ullmann-type re-
action, N-arylation, nucleobase
biological systems.17 The synthesis of N-aryl nucleobases
generally involves, (i) the heterocyclization of suitable
precursors,18 (ii) the reaction of nucleobases with diaryl-
iodonium salts,19 and (iii) nucleophilic aromatic substitu-
The high cost, toxic effects, and the problem of waste dis-
tion (SNAr) reactions of electron-deficient aryl halides
posal associated with many transition metals have led to
with nucleobases.20 Recently, arylboronic acids in the
an increased attention toward the development of hetero-
presence of simple cupric salts have been frequently used
geneous catalysts. The immobilization of active catalysts
for the direct N-arylation of nucleobases.21 However,
on the heterogonous supports provides certain additional
drawbacks such as low yields of product, long reaction
characteristics, including selectivity, thermal stability,
time, the use of expensive or less available arylboronic ac-
ease of separation from the reaction mixture, recyclabili-
ids, low selectivity, oxidation, and deboronation of aryl-
ty, and reusability of catalysts.1–4 Being one of the most
boronic in the presence of copper(II) and H2O are usually
versatile metals for catalysis, copper has been widely em-
observed in the above methods. On the other hand, when
ployed in a variety of organic reactions. The copper(I)-
free copper cation is applied, the complexation of purine
catalyzed Huisgen’s 1,3-dipolar cycloaddition reaction5
nucleobase (i.e., adenine) with copper salt is likely.
and Ullmann-type coupling of various nucleophiles with
Hence, there is still an urgent demand for establishing a
aryl halides are the most distinguished organic transfor-
novel and efficient method for easy accessing the N-aryl
mations using copper catalysts.6
nucleobases. In the light of wide diversity and availability
Polymers,7 charcoal,8 cellulose,9 zeolites,10 alumina,11 and
of aryl halides compared with arylboronic acids, the direct
silica gel12 have been widely used as the solid supports in
N-arylation of nucleobases with the aryl halides seems to
the preparation of copper catalysts. Among the applied
solid supports for the preparation of heterogeneous cata-
lysts, silica gel is usually preferred. Silica gel exhibits
many advantageous properties, including high surface
be a suitable and attractive strategy.
In continuation of our ongoing research on nucleoside
chemistry,22 we disclose here the design and synthesis of
copper nanoparticle-doped silica cuprous sulfate (CN-
DSCS) (Scheme 1) as a novel and efficient heterogeneous
catalyst for the Ullmann-type N-arylation of nucleobases
and/or azole derivatives with aryl halides (Scheme 2).
SYNTHESIS 2011, No. 23, pp 3915–3924
x
x.
x
x
.
2
0
1
1
Advanced online publication: 21.09.2011
DOI: 10.1055/s-0030-1260236; Art ID: Z74311SS
© Georg Thieme Verlag Stuttgart · New York

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M. N. Soltani Rad et al.
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O2 (8%) in Ar
SiO2
400 °C, 1 h
SiO2
SiO2
OH
r.t.
OH
SiO2
OSO3H
+ HCl
+ ClSO
3H (neat)
silica sulfuric acid (SSA)
SiO2
OSO3Cu
CN-DSCS
1) ultrasound, H2O, 1 h, r.t.
OSO3H
+
SiO2
Figure 1 (a) SiO2, (b) SSA and (c) CN-DSCS
2) CuI/H2O, ultrasound, H2O, 6 h, r.t.
Hl
Scheme 1 Routes to prepare the copper nanoparticle-doped silica
cuprous sulfate (CN-DSCS)
Characterization of Catalysis Nanostructure
Figures 2, 3, and 4 indicate the scanning electron micros-
copy (SEM), transmission electron microscopy (TEM),
and atomic force microscopy (AFM) images of CN-
DSCS, respectively. Good correlation was observed for
copper nanoparticles characterized by different micro-
scopic techniques. In addition, the histogram diagram
(Figure 5) presents the frequent distribution of CN-DSCS
based on the AFM image (Figure 4). Regarding this histo-
gram, the maximum diameter distributed for the copper
catalyst is around 25 nm. The X-ray diffraction (XRD)
pattern of CN-DSCS is shown in Figure 6. Based on the
XRD pattern, the strong peaks corresponds to copper
nanostructure, for which the related data are summarized
in Table 1.
X
N
CN-DSCS, DBU
+
G
G
N
DMF, reflux, 4–12 h
H
X = Br, I
G = Me, OMe, etc.
O
NH2
N
N
NH
N
etc.
,
,
,
=
N
H
N
N
O
N
N
H
H
H
Scheme 2 Ullmann-type N-arylation of nucleobases and/or azole
derivatives with aryl halides using CN-DSCS
Preparation of CN-DSCS
The process for the preparation of CN-DSCS is shown in
Scheme 1. According to Scheme 1, the synthesis of CN-
DSCS is carried out from freshly prepared silica sulfuric
acid (SSA). The preparation of SSA was previously re-
ported by mixing the normal SiO2 and ClSO3H.23a How-
ever, to our experience, more pleasant result was obtained
when activated SiO2 was used to react with ClSO3H. In
this context, the silica was first activated by a flow of 8%
O2 in argon atmosphere for 1 hour at 400 °C in a furnace.
Then, the activated SiO2 was introduced to an adequate
amount of ClSO3H. Slightly excess of ClSO3H was added
to ensure the enrichment of all active site (i.e., OH) on
SiO2. At this stage, no further HCl gas was evolved. The
amount of H+ in SSA was determined by simple acid–base
back-titration. The amount of H+ in SSA was evaluated to
be 0.05 gram (0.13 mmol) of silica sulfuric acid.23b
Figure 2 Scanning electron microscopy (SEM) image of CN-DSCS
On this basis, CN-DSCS was synthesized from a suspen-
sion of SSA in demineralized water, which was primarily
exposed to ultrasonic irradiation at room temperature for
one hour. A solution of copper(I) iodide in demineralized
water, which was previously enriched with portions of
NaI solution (see the experimental section) was then
mixed with SSA and the mixture exposed to ultrasonic ir-
radiation for six hours at ambient temperature. Filtration
followed by washing and drying provided CN-DSCS as a
dark-powdered solid (Figure 1).
Figure 3 Transmission electron microscopy (TEM) image of CN-
DSCS
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Copper Nanoparticle-Doped Silica Cuprous Sulfate
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Table 1 Analysis of XRD Patterns Related to CN-DSCS after Re-
using for Three Times
2q
Matrix and morphology
Ref.
Cu
Cu(I)
25.5
30.5
38.5
57.2
68.5
72.1
–
(111)
(200)
(220)
(222)
(331)
(420)
8
8a
8a
7
–
(111)
–
–
–
7
10a
The copper nanoparticle size was also recognized from X-
ray line broadening using Debye–Scherrer formula as:
D = 0.9 l/b1/2 cos q, where D, l, b1/2, and q are the average
crystalline size, the applied X-ray wavelength, the angular
line width at half maximum intensity, and the Bragg’s an-
gle, respectively.24
Figure 4 Atomic force microscopy (AFM) image of CN-DSCS
With regard to the peak of copper nanoparticles and the
corresponding plane of copper (200) for l = 1.085 Å, the
average size of copper nanoparticles is estimated at
around 28 nm, which is in good agreement with the results
attained by the microscopic techniques.
Figure 7 indicates the thermogravimetric analysis (TGA)
of CN-DSCS. Based on the TG thermogram, a decrease in
weight of CN-DSCS is observed at temperature around
95 °C and it is attributed to desorption of water and other
species from CN-DSCS. The decrease in weight is also
observed around 230 °C related to desorption of sulfur
from CN-DSCS and formation of sulfur dioxide. Further-
more, the increase in weight around 380 °C is also ratio-
nalized to the oxidation of copper nanoparticles and
formation of copper oxides. The sharp decrease in weight
at 850 °C is assigned to the decomposition of silica ma-
trix. Finally, the last part of the thermogram (the flexure
obtained at the low weight percentages) shows the quanti-
ty of copper oxide and reveals the amount of copper nano-
particles on silica. The estimated value was 6.12%.
Figure 5 Histogram diagram representing the average diameter of
CN-DSCS
Figure 6 Smoothed X-ray diffraction (XRD) pattern of CN-DSCS
From Table 1, the peak corresponds to the plane of (111)
indicates the copper(0) formation in relation with the dis-
proportionation reaction of copper(I) in a polar solution.
Figure 7 Thermogravimetric (TG) analysis of CN-DSCS
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M. N. Soltani Rad et al.
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Table 2 Effect of Various Solvents on the Conversion of Uracil into
N-Phenyluracil Using CN-DSCS
O
O
CN-DSCS, DBU
solvent, reflux
HN
HN
Ph
I
+
O
N
H
O
N
Ph
Entry
Solvent
MeCN
NMP
Time (h)
Yield (%)a
1
2
3
4
5
6
7
18
10
9
10
43
DMSO
DMF
51
Figure 8 FT-IR spectrum of freshly prepared CN-DSCS
8
60
HMPA
toluene
THF
10
24
24
45
The FT-IR spectrum of the CN-DSCS catalyst is shown in
Figure 8. The solid state IR spectrum of catalyst was re-
corded using the KBr disk technique. Metal oxides gener-
ally give absorption bands below 1000 cm–1 and in this
case, an asymmetric band at 551 cm–1 corresponds to Cu–
O bond. Furthermore, a band at 671 cm–1 is assigned to S–
O stretching. A major broad-sharp peak at 900–1200 cm–1
is a set of overlapped bands consisting of several signals,
including symmetric and antisymmetric stretching modes
of Si–O–Si, asymmetric and symmetric stretching modes
of O=S=O, and also symmetric band of Cu(I or II)–O
bonds.25
The bands at 1500–1700 cm–1 correspond to water mole-
cules adsorbed on CN-DSCS and combination of the CN-
DSCS vibration modes. The spectrum also shows the ab-
sorption around 3441 cm–1, which is assigned to stretch-
ing vibration of different types of hydroxyl groups.
NRb
NRb
a Isolated yield.
b No reaction.
The choice of base for activation of nucleobases is of great
significance. We tested the potency of several organic and
inorganic bases on the model reaction (Table 3). From the
results shown in Table 3, among the examined bases,
DBU (Table 3, entry 6) was found to be the best base for
the progress of the reaction, whereas K2CO3, Cs2CO3, and
DBN (entries 2, 3, and 7) afforded moderate yields of N-
phenyluracil. Other bases applied in the experiment did
not demonstrate any satisfactory results.
The temperature has undeniable role in the improvement
of Ullmann type coupling reactions. Therefore, to exam-
ine the effect of temperature, the model reaction was con-
Ullmann-Type N-Arylation of Nucleobases Using CN-
DSCS
After synthesis and characterization of the CN-DSCS, the
catalytic activity of CN-DSCS in the Ullmann-type N-
arylation reactions of various N-heterocyclic compounds
was examined. In this context, many structurally diverse
nucleobases and/or azole derivatives were coupled in the
presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in
refluxing DMF (Scheme 2).
Table 3 Effect of Various Bases on the Conversion of Uracil into
N-Phenyluracil Using CN-DSCS
O
O
CN-DSCS, base
DMF, reflux
HN
HN
Ph
I
+
O
N
H
O
N
Ph
The first step of this synthetic approach was started by op-
timizing the reaction conditions. The coupling of uracil
and iodobenzene was chosen as a model reaction. Initial-
ly, the effect of various solvents on the model reaction us-
ing CN-DSCS (0.3 g, 0.05 mol%), and DBU was studied
(Table 2). The results in Table 2 show that the type of sol-
vent has a significant role in the progress of the reaction.
Among the examined solvents, DMF (Table 2, entry 4)
demonstrated the best result and it was the solvent of
choice for all reactions. Use of aprotic solvents, like NMP,
DMSO, and HMPA (entries 2, 3, and 5) resulted in mod-
erate yields of N-phenyluracil. Other solvents were not
suitable enough to progress the reaction, even if the reac-
tion time was allowed to be prolonged.
Entry
Base
Time (h)
Yield (%)a
1
2
3
4
5
6
7
8
MgO
24
9
trace
55
K2CO3
Cs2CO3
DABCO
DMAP
DBU
9
52
16
16
8
10
15
60
DBN
10
10
45
Et3N
37
a Isolated yield.
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Copper Nanoparticle-Doped Silica Cuprous Sulfate
3919
ducted at different temperatures. Increases in temperature To realize the scope of this protocol, the optimized reac-
remarkably affected the Ullmann-type N-arylation rate tion condition was applied to diverse nucleobases and aryl
and considerably improved the yield of corresponding N- halides (Table 4). According to Table 4, CN-DSCS
phenyluracil. The admissible result was obtained when proved to be an efficient nanocatalysis for coupling of
the coupling reaction was carried out in refluxing DMF various aryl halides (X = I, Br) with purine and pyrimi-
for eight hours yielded N-phenyluracil in 60%.
dine nucleobases in reasonable to good yields. All synthe-
sized compounds were fully characterized, and their
structures were confirmed by spectroscopic analysis
methods, including 1H and 13C NMR, elemental analysis,
mass, IR spectroscopy or compared to those of authentic
samples.
The optimized stoichiometric ratios of nucleobase/aryl
halide/DBU for the conversion of uracil into N-phenyl-
uracil were found to be 1:1.3:2. One should be aware of
employing the correct aryl halide ratio. The increment in
the mole ratio of aryl halide can lead to the formation of
biaryl adducts in the presence of copper(I).
Table 4 Ullmann-Type N-Arylation of Nucleobases and/or Azole Derivatives Using ArX/CN-DSCS/DBU in Refluxing DMF
Entry
Nucleobase
ArX
Producta
Time (h) Yield (%)b
O
O
I
HN
119,21f
8
9
60
HN
O
N
O
N
H
O
N
O
Br
HN
219,21f
56
HN
O
O
N
H
O
N
O
Cl
HN
319,21f
72
trace
HN
O
O
N
H
O
N
I
HN
O
419b
8
58
O
HN
O
N
H
Cl
Cl
O
I
HN
O
519b,21f
7
61
O
N
HN
O
N
H
OMe
OMe
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3920
M. N. Soltani Rad et al.
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Table 4 Ullmann-Type N-Arylation of Nucleobases and/or Azole Derivatives Using ArX/CN-DSCS/DBU in Refluxing DMF (continued)
Entry
Nucleobase
ArX
Producta
Time (h) Yield (%)b
O
I
HN
O
619b,21f
9
52
O
O
O
O
N
HN
O
N
H
O
N
HN
Br
O
719b,21f
11
49
HN
O
N
H
O
N
HN
Cl
O
819b,21f
72
12
12
trace
HN
HN
HN
O
O
O
N
H
O
N
O
I
HN
921f
35
N
H
O
N
I
HN
O
OMe
1021f
38
O
OMe
N
H
NH2
N
N
I
NH2
1121c
8
55
O
N
O
N
H
Cl
Cl
NH2
NH2
I
N
1221c
8
53
N
O
N
O
N
H
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Copper Nanoparticle-Doped Silica Cuprous Sulfate
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Table 4 Ullmann-Type N-Arylation of Nucleobases and/or Azole Derivatives Using ArX/CN-DSCS/DBU in Refluxing DMF (continued)
Entry
1321c
Nucleobase
ArX
Producta
Time (h) Yield (%)b
NH2
NH2
N
Br
N
10
50
O
N
N
O
N
H
NH2
N
N
N
I
NH2
1421c,e,f
12
48
N
N
N
H
N
OMe
OMe
NH2
N
N
N
NH2
N
I
N
1521f
12
45
65
N
N
N
H
OMe
OMe
O
N
I
H
N
O
N
Me
1618g,21i
6
N
Me
N
N
N
O
N
O
Me
Me
OMe
O
I
H
N
Me
O
O
1726a
6
67
N
Me
O
N
N
N
N
N
Me
OMe
I
N
Me
O
O
N
Me
Me
N
N
HN
N
18
19
7
7
67
68
N
N
O
O
N
O
Me
Me
MeO
O
I
O
Me
Me
N
N
HN
N
N
N
N
O
N
Me
OMe
I
Me
N
N
N
2026b
6
70
N
H
CN
CN
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M. N. Soltani Rad et al.
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Table 4 Ullmann-Type N-Arylation of Nucleobases and/or Azole Derivatives Using ArX/CN-DSCS/DBU in Refluxing DMF (continued)
Entry
2126b
Nucleobase
ArX
Producta
Time (h) Yield (%)b
N
N
Br
N
4
4
74
77
N
H
CN
CN
N
Br
N
N
2226b
N
H
a All products were characterized by 1H and 13C NMR, IR, CHN, and MS analysis. For known compounds they were consistent with those
reported in the literature (cf. references provided in the entry).
b Isolated yield.
From Table 4, aryl halides (X = I, Br) having both elec- Table 5 indicate, the catalyst can be reused for many con-
tron-rich or electron-deficient residues can undergo the secutive runs without remarkable decrease in its catalytic
Ullman-type N-arylation of nucleobases. Use of chlo- reactivity.
robenzene as an arylating agent led to poor yields of de-
sired products (Table 4, entries 3, 8). The low yields
corresponded to aryl chlorides are attributed to higher
bond dissociation energy. For example, when both chlo-
Table 5 Reusability of CN-DSCS in Successive Trials for the Syn-
thesis of N-Phenyluracil
O
O
rine and iodine are present on aryl ring, only iodine atom
, DBU
CN-DSCS
HN
HN
is replaced by nucleobase (Table 4, entries 4, 11). The
lower yields attained by the ortho-substituted aryl iodides
compared with other aryl iodides is naturally correlated to
steric hindrance present at ortho substituents (Table 4, en-
tries 9 and 10). Moreover, there was no considerable dis-
crepancy between the reactivity of aryl iodides and aryl
bromides for nucleobases in our experiment. To illustrate
the scope of this method, the optimized reaction condi-
tions were also applied to other N-heterocycles including
benzimidazole and imidazole.
Ph
I
+
DMF, reflux
O
N
O
N
H
Ph
Run
1
Time (h)
Yield (%)a
8
8
60
58
53
49
47
2
3
9
4
9.5
10
Good yields of the corresponding adducts were obtained
using CN-DSCS (Table 4, entries 20–22). Good regiose-
lectivity was also observed in the N-arylation of nucleo-
bases using CN-DSCS. The N-arylation of purine and
pyrimidine nucleobases was chiefly achieved at N9 and
N1 sites respectively, whereas the corresponding N7-aryl
for purines and/or N1,N3-diaryl derivatives for pyrim-
idines were obtained in trace amounts (<5%).
5
a Isolated yield.
To prove the recoverability and demonstrate the thermal
as well as chemical stability of CN-DSCS, analytical tech-
niques such as inductively coupled plasma (ICP) and
TGA instrument were used for measuring the copper
amounts before and after five successive uses of CN-
DSCS. Based on the ICP results, the amount of copper
bonded on fresh CN-DSCS was evaluated to 6.12%. This
value was also calculated to 6.14%, according to TG anal-
ysis. The small difference between obtained results from
ICP and TGA analyses is attributed to sample pretreat-
ment before ICP analysis. Based on the ICP results, the
amount of copper species was diminished to 6.11% after
five sequential reuses. The ICP analysis has revealed the
capability of applied procedure for synthesis of copper
nanoparticles. Additionally, the ICP analysis has en-
Reusability of CN-DSCS
The reusability of the CN-DSCS was studied during the
synthesis of N-phenyluracil (Table 5, entry 1). In this con-
text, prior to use and also final testing of the catalyst for
determination of its activity in many subsequent runs, the
catalyst was recycled from the reaction mixture through a
sintered glass funnel (vacuum filtration). The catalyst was
then washed successively with THF (three times) and
dried in a vacuum oven at 100 °C for 30 minutes. The cat-
alyst was tested for five consecutive runs and through
each run, no fresh catalyst was added. As the results in
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Copper Nanoparticle-Doped Silica Cuprous Sulfate
3923
W) at r.t. After filtration of CN-DSCS, the dark solid reagent was
washed by distilled H2O (3 × 10 mL). The CN-DSCS was then dried
under vacuum at 80 °C.
dorsed the recoverability of CN-DSCS without significant
leakage from the silica matrix. As it is well indicated, the
amount of leached copper from CN-DSCS is negligible
(0.01% after five runs) and it is reasoned due to strong
ionic bonds present between copper cations and sulfate
group on the surface of SSA. This characteristic of CN-
DSCS demonstrates its superiority in comparison with
usual catalysts, which normally are prepared by immobi-
lization of copper species on solid supports and/or poly-
mers.
Ullmann-Type N-Arylation of Nucleobases; General Procedure
In a double-necked 100 mL round-bottomed flask equipped with a
condenser was added a mixture consisting of appropriate nucleo-
base or other N-heterocycle (0.01 mol), DBU (0.02 mol), aryl halide
(0.013 mol), and CN-DSCS (0.3 g, 0.05 mol%) in DMF (30 mL).
The mixture was heated at reflux, and in most cases, darkening of
reaction media had occurred. Heating was continued until TLC in-
dicated no further progress in the conversion (Table 4). Then, the
catalyst was filtered off and the filtrate was evaporated under vacu-
um to remove the solvent. The remaining foam was dissolved in
CHCl3 (100 mL) and subsequently washed with H2O (2 × 100 mL).
The organic layer was dried (Na2SO4) and evaporated. The crude
product was purified by column chromatography on silica gel elut-
ing with proper solvents (Table 4).
In summary, we have described the preparation and char-
acterization of copper nanoparticle-doped silica cuprous
sulfate (CN-DSCS) as a highly efficient heterogeneous
catalysis for Ullmann-type N-arylation of nucleobases
with aryl halides. In this synthetic methodology, CN-
DSCS was proved to be a useful catalyst for coupling of
purines, pyrimidines, and/or azoles derivatives with ArX
(X = Br, I) in the presence of DBU and DMF. Using CN-
DSCS, reasonable to good yields of N-aryl heterocyclic
adducts were obtained in favorable regioselectivities. CN-
DSCS demonstrates to be an efficient, thermally and
chemically stable, environmental compatible, and low
cost catalysis that can be easily prepared, recycled, and re-
used for many consecutive runs without decrease in the
catalytic reactivity.
3,7-Dimethyl-1-phenyl-1H-purine-2,6(3H,7H)-dione (Table 4,
entry 18)
Column chromatography on silica gel (EtOAc–n-hexane, 2:1) af-
forded the product as a white solid; yield: 1.64 g (64%); mp 218.5
°C.
IR (KBr): 3036, 2972, 1720, 1707, 1648, 1451 cm–1.
1H NMR (250 MHz, CDCl3): d = 3.61 (s, 3 H, N3-CH3), 3.94 (s, 3
H, N7-CH3), 7.22–7.26 (m, 2 Harom), 7.44–7.50 (m, 3 Harom), 7.55 (s,
1 H, H-8, theobromine).
13C NMR (62.5 MHz, CDCl3): d = 27.12, 31.25, 106.53, 123.29,
125.83, 129.16, 130.35, 146.50, 148.07, 150.64, 165.70.
All preliminary chemicals were purchased from Fluka, Merck, and/
or Sigma-Aldrich. Preparation of SSA was conducted according to
the procedure in literature.23 Solvents were purified and dried by
standard procedures, and stored over 3Å molecular sieves. Reac-
tions were followed by TLC using SILG/UV 254 silica-gel plates.
Column chromatography was performed on silica gel 60 (0.063–
0.200 mm, 70–230 mesh, ASTM). The TGA of CN-DSCS was an-
alyzed using a lab-made thermogravimetric (TG) analyzer instru-
mentation system. The transmission electron microscopy was
employed using TEM (CN-10, Philips, 100 KV). The scanning
electron micrograph was attained using SEM (XL-30 FEG, Philips,
20 KV) instrument. An atomic force microscopy (AFM, DME-
SPM, version 2.0.0.9) was also used for AFM image. Spectroscopic
techniques such as inductively coupled plasma (ICP) and patterned
X-ray diffraction (XRD, D8 Advance, Bruker AXS) were employed
for characterization of CN-DSCS. Melting points were measured
using a Büchi-510 apparatus in open capillaries and are uncorrect-
ed. FT-IR spectra were obtained using a Shimadzu FT-IR-8300
spectrophotometer. 1H and 13C NMR spectrum was attained using a
Bruker Avance-DPX-250 spectrometer operating at 250/62.5 MHz,
respectively (d in ppm, J in Hz). GC/MS were performed on a Shi-
madzu GC/MS-QP 1000-EX apparatus (m/z, %). Elemental analy-
ses were conducted on a Perkin–Elmer 240-B microanalyzer. Full
analytical data are provided for novel products and references are
given for known compounds (Table 4).
MS (EI): m/z = 256 (19.8, [M+]).
Anal. Calcd for C13H12N4O2: C, 60.93; H, 4.72; N, 21.86. Found: C,
60.98; H, 4.81; N, 21.80.
1-(4-Methoxyphenyl)-3,7-dimethyl-1H-purine-2,6(3H,7H)-di-
one (Table 4, entry 19)
Column chromatography on silica gel (EtOAc–n-hexane, 2:1) af-
forded the product as a white solid; yield: 1.94 g (68%); mp 182.5
°C.
IR (KBr): 3050, 2951, 1720, 1705, 1653, 1475, 1210 cm–1.
1H NMR (250 MHz, CDCl3): d = 3.59 (s, 3 H, N3-CH3), 3.82 (s, 3
H, N7-CH3), 3.95 (s, 3 H, OCH3), 6.98 (d, J = 7.9 Hz, 2 Harom), 7.13
(d, J = 7.9 Hz, 2 Harom), 7.53 (s, 1 H, H-8, theobromine).
13C NMR (62.5 MHz, CDCl3): d = 28.36, 30.16, 53.91, 105.48,
115.03, 122.81, 124.20, 144.85, 149.26, 151.27, 157.31, 164.62.
MS (EI): m/z = 286 (16.2, [M+]).
Anal. Calcd for C14H14N4O3: C, 58.73; H, 4.93; N, 19.57. Found: C,
58.65; H, 4.98; N, 19.43.
Acknowledgment
We thank Shiraz University of Technology and Shiraz University
Research Councils for partial support of this work.
Copper Nanoparticle-Doped Silica Cuprous Sulfate (CN-DSCS)
For the preparation of CN-DSCS, SSA (3.0 g) was dispersed in tri-
ply distilled H2O (50 mL). The suspension was then sonicated for 1
h in a beaker inside a sonication bath (frequency 100 MHz, 80 W)
at r.t. The suspension was left for about 30 min to be deposited and
separated. An aqueous solution of 1.0 mM of CuI was prepared by
dissolving CuI in triply distilled H2O (100 mL) and it was enriched
by the addition of 0.02 M aq NaI (10 mL). Then, this solution was
added to the SSA dropwise, during which the suspension was soni-
cated in a beaker inside a sonication bath (frequency 100 MHz, 80
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