Sulfuric acid functionalized silica-coated magnetic nanoparticles: Preparation and application in synthesis of mono-, Di- and tri[bis(6- aminopyrimidinyl)methanes]

Article abstract of DOI:10.1055/s-0033-1339761

Sulfuric acid functionalized silica-coated magnetic nanoparticles (SSA-MNPs) were prepared by a simple method and evaluated as efficient catalysts for the condensation reaction of 6-amino-1,3-dimethyluracil with mono-, di-, or trialdehydes to give the cor

Full text of DOI:10.1055/s-0033-1339761

3300▌
PAPER
paper
Sulfuric Acid Functionalized Silica-Coated Magnetic Nanoparticles: Prepara-
tion and Application in Synthesis of Mono-, Di- and Tri[bis(6-aminopyrimidi-
nyl)methanes]
Mono-, Di- and Tri[bis(6-aminopyrimidinyl)methanes]
Ali Reza Karimi,* Zeinab Dalirnasab, Marzie Karimi, Fatemeh Bagherian
Department of Chemistry, Faculty of Science, Arak University, Arak 38156-8-8349, Iran
Fax +98(861)4173406; E-mail: a-karimi@araku.ac.ir
Received: 24.06.2013; Accepted after revision: 16.08.2013
OH
OSO3H
Abstract: Sulfuric acid functionalized silica-coated magnetic
nanoparticles (SSA-MNPs) were prepared by a simple method and
evaluated as efficient catalysts for the condensation reaction of 6-
amino-1,3-dimethyluracil with mono-, di-, or trialdehydes to give
the corresponding mono-, di- and tri[bis(6-aminopyrimidinyl)meth-
anes]. The catalyst was simply recycled by the use of an external
magnetic field and could be reused five times without significant
loss of activity or mass.
Fe3O4
MNP
ClSO3H
Fe3O4
Fe3O4
CA
Si(OEt)4
NH4OH
SSA-MNP
MNP/SiO2
Fe3O4
CMNP
Key words: nanostructures, catalysis, condensation, aldehydes,
heterocycles, ultrasound
Scheme 1 Preparation of sulfuric acid functionalized silica-coated
magnetic nanoparticles (SSA-MNPs); CA = citric acid; CMNP =
citrate-functionalized MNP.
Recently, much attention has been focused on the prepa-
ration of acid-functionalized catalysts. Zolfigol prepared
sulfuric acid functionalized silica (SSA) by treatment of
silica gel with chlorosulfonic acid,1 and SSA has since
been shown to be an extremely useful catalyst in various
organic transformations.2 The preparation of acid-func-
tionalized magnetic nanoparticle (MNP) catalysts has also
become a significant area of research that has attracted
worldwide attention.3–6 As acid catalysts, magnetic
nanoparticles have many advantages, such as a large sur-
face area, low mass-transfer resistance, and ease of recov-
ery by the use of a magnetic field. The surfaces of silica-
coated MNPs can be functionalized to accommodate a
wide variety of acid catalysts, for example, by oxidation
of immobilized thiols to form sulfonic acids, hydrolysis of
immobilized sulfonic acid chlorides, sulfonation of sup-
ported phenyl groups, ring opening of perfluorosulfonic
acid sulfones, immobilization of perfluorosulfonic acid
triethoxysilanes,3 grafting of chlorosulfuric acid onto
amino-functionalized Fe3O4 nanoparticles,6 or reaction of
silica-coated γ-Fe2O3 with chlorosulfonic acid.7
are key intermediates in the synthesis of purines, which
constitute the basic nuclei of many drugs, such as caf-
feine, penciclovir, theobromine, and theophylline.10 Or-
ganic compounds containing pyrimidine scaffolds are
important targets and are known to show diverse biologi-
cal and pharmaceutical activities.11 Heterocyclic
structures bearing a pyrimidine moiety, such as dihydro-
pyrimidines,12 furopyrimidines,13 and pyrazolopyrimi-
dines,14 have long been important in the pharmaceutical
industry.
The reaction of 6-amino-1,3-dimethyluracil with alde-
hydes affords the corresponding bis(6-aminopyrimidi-
nyl)methanes, a useful class of organic compounds.
Because of the pharmacological interest in pyrimidinones,
synthesis of such compounds has become very important,
and was initially achieved by the reaction of 6-aminoura-
cils with aldehydes.15
2,4,6-Trisubstituted 1,3,5-triazine derivatives have found
widespread applications in diverse fields, such as textiles,
plastics, rubber,16 and electroluminescent devices.17 The
compounds have been used in the development of organic
light-emitting diodes,18 liquid crystalline materials,19 and
nonlinear optical materials.20 Therefore, the development
of techniques for the synthesis and functionalization of
2,4,6-trisubstituted 1,3,5-triazines has been a focus of re-
search over many years.16,21
We synthesized sulfuric acid functionalized silica-coated
magnetic nanoparticles (SSA-MNPs) by functionalization
of silica-coated magnetic nanoparticles with chlorosul-
fonic acid (Scheme 1), and we examined their catalytic
behavior in the reaction of 6-amino-1,3-dimethyluracil
with various aldehydes.
6-Amino-1,3-dimethyluracil and its fused derivatives8 are
versatile building blocks for the synthesis of several bio-
active nitrogen-containing heterocycles.9 6-Aminouracils
Although the pseudo three-component reaction of 6-ami-
nouracil with monoaldehydes has been previously inves-
tigated,15 surprisingly there are no reports on the reaction
of 6-aminouracils with di- or trialdehydes to give di- and
tri[bis(6-aminopyrimidinyl)methanes], respectively. Be-
cause of the biological activity of bis(6-aminopyrimidi-
SYNTHESIS 2013, 45, 3300–3304
Advanced online publication: 27.09.2013
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8
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1
1
4
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DOI: 10.1055/s-0033-1339761; Art ID: SS-2013-Z0436-OP
© Georg Thieme Verlag Stuttgart · New York

PAPER
Mono-, Di- and Tri[bis(6-aminopyrimidinyl)methanes]
3301
Table 1 Optimization of the Synthesis of 3aa
nyl)methanes and our interest in the synthesis of
heterocyclic compounds,22 we have developed a simple
and efficient method for the preparation of mono-, di-, and
tri[bis(6-aminopyrimidinyl)methanes] by using SSA-
MNPs as efficient catalysts for the pseudo three-, five-
and seven-component reactions of 6-amino-1,3-dimethyl-
uracil with mono-, di- and trialdehydes, respectively, in
the presence of ultrasound at 50 °C (Scheme 2).
Entry
SSA-MNPs (g)
Solvent
Yield (%)
1
–
EtOH
EtOH
EtOH
EtOH
EtOH
H2O
10
65
75
95
79
30
85
55
20
40
2
0.03
0.06
0.10
0.15
0.10
0.10
0.10
0.10
0.10
3
4
To optimize the reaction conditions, we investigated the
typical reaction of 4-chlorobenzaldehyde (2a; 1 mmol)
with 6-amino-1,3-dimethyluracil (2 mmol) under various
conditions (Table 1).
5
6
7
MeCN
DMF
THF
Initially, we examined the effect of the catalyst concentra-
tion on the yield by varying the amount of catalyst from 0
to 0.15 g in the presence of ultrasound at 50 °C. After one
hour, with 0, 0.03, 0.06, 0.1, or 0.15 gram of SSA-MNP,
we obtained yields of 10, 65, 75, 95, and 83%, respective-
ly (Table 1, entries 1–5). Next we examined the role of the
solvent (entries 4 and 6–10). The reaction barely proceed-
ed in tetrahydrofuran (entry 9), whereas the reaction in
ethanol (entry 4) gave the product in high yield with near-
ly complete conversion. We therefore selected ethanol as
the reaction solvent for subsequent investigations. The op-
timal reaction conditions involve the use of 0.1 gram of
SSA-MNP in ethanol at 50 °C.
8
9
10
DMSO
a Reaction conditions: 4-ClC6H4CHO (1 mmol), 6-amino-1,3-dimeth-
yluracil (2 mmol), 50 °C, 1 h, ultrasound.
to establish the scope of the catalytic transformation
(Scheme 2 and Table 2)
The mono[bis(6-aminopyrimidinyl)methanes] 3a–d were
obtained in high yields by the pseudo-three-component
condensation of 6-amino-1,3-dimethyluracil (2 mmol)
with monoaldehydes 2a–d (1 mmol), respectively, in the
We next examined the reactions of a wide range of mono-
aldehydes 2a–d, dialdehydes 2e,f, and trialdehydes 2g–i
2a–d
2e,f
R1
R2
Me
O
N
CHO
R3
N
OHC
R3
OHC
O
R2
R1
Me
Me
O
O
N
Me
O
NH2
O
N
2e = terephthalaldehyde
2f = isophthalaldehyde
2a R1 = R2 = H; R3 = Cl
2b R1 = R3 = H; R2 = NO2
2c R1 = R2 = H; R3 = NO2
2d R1 = R2 = Cl; R3 = H
N
NH2
NH2
N
NH2
Me
NH2
Me
O
Me
O
Me
1
OMe
CHO
NO2
N
N
NH2
NH2
OAr
O
N
N
O
2g Ar =
Me
O
Me
O
N
N
Me
Me
N
N
O
N
N
O
2h Ar = 4-OHCC6H4
2i Ar = 3-OHCC6H4
ArO
N
OAr
3a–d
Me
Me
2g,i
3e,f
O
Me
O
N
O
N
Me
N
Me
Me
Me
N
N
N
H2N
Me
Me
Me
O
H2N
O
O
O
H2N
O
O
O
O
O
N
Me
Me
Me
O
Me
Me
O
N
N
O2N
O
Me
O
N
N
N
Me
Me
N
N
N
O
O
NH2
O
N
H2N
N
O
O
O
NH2
NH2
H2N
N
N
O
O
N
H2N
N
O
N
Me
OMe
N
N
OMe
Me
Me
O
Me
NH2
Me
Me
O
N
N
N
N
N
N
O
O
N
NH2
O
O
N
NH2
O
N
O
NO2
Me
Me
Me
NH2
N
MeO
NH2
NO2
O
N
NH2
NH2
NH2
NH2
Me
O
Me
O
Me
O
Me
Me
O
O
N
N
N
N
Me
N
N
N
O
O
N
N
O
O
N
O
Me
O
Me
Me
Me
Me
3g
3h
3i
Scheme 2 Synthesis of mono-, di- and tri[bis(6-aminopyrimidinyl)methanes] 3a–i catalyzed by SSA-MNPs
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 3300–3304

3302
A. R. Karimi et al.
PAPER
Table 2 SSA-MNP-Catalyzed Synthesis of Mono-, Di- and Tri[bis(6-aminopyrimidinyl)methanes]a
Entry
Aldehyde
Product
Time (h)
Yield (%)
mp (°C)
1
2
3
4
5
6
7
8
9
2a
2b
2c
2d
2e
2f
3a
3b
3c
3d
3e
3f
1
1
1
1
4
4
5
5
5
95
90
92
87
83
80
87
88
85
<300b
248–250
<300b
275–277
<300
284–286
291–294
285–288
265–268
2g
2h
2i
3g
3h
3i
a Reaction conditions: EtOH, 50 °C, ultrasound.
b Lit.15 >300 °C.
presence of SSA-MNPs (0.1 g) as heterogeneous catalyst to O–H stretching of the SO3H group appeared at 3300–
in ethanol (8 mL) at 50 °C with ultrasound irradiation. 3600 cm–1.
The di[bis(6-aminopyrimidinyl)methanes] 3e–f were sim-
The sizes of nanoparticles were determined by scanning
ilarly prepared by pseudo-five-component reaction of 6-
electron microscopy (SEM). The average size was about
amino-1,3-dimethyluracil (5 mmol) with terephthalalde-
39 nm. The thermal properties of the SSA-MNPs were an-
hyde (2e; 1 mmol) or isophthalaldehyde (2f; 1 mmol) in
alyzed by thermogravimetry at 20–850 °C under nitrogen.
the presence of SSA-MNPs (0.1 g) in ethanol (15 mL).
The primary weight loss at temperatures up to 160 °C was
The same procedure was used to prepare the tri[bis(6-ami-
related to the removal of physically adsorbed solvent. The
nopyrimidinyl)methanes] 3g–i by pseudo-seven-compo-
rate of weight loss between 160 and 540 °C was relatively
slow, showing that SSA-MNPs have a high thermal stabil-
nent reaction of trialdehydes 2g–i (1 mmol), respectively,
with 6-amino-1,3-dimethyluracil (7 mmol). All products
ity. The maximum rate of lost weight of the SSA-MNPs
were characterized by means of melting point measure-
began at 540 °C. There was a well-defined mass weight
1
ments and by Fourier-transform IR, H NMR, and 13C
loss of 39% between 160 and 670 °C; this was ascribed to
NMR spectroscopy. No byproducts were formed, and the
the breakdown of the sulfuric acid moieties, in agreement
time required for the reactions was reduced from four
with the results of elemental analysis of SSA-MNPs (S,
hours to one hour by the use of SSA-MNP catalysts.
14.88%).
The sulfuric acid functionalized silica magnetic nanopar-
X-ray diffraction patterns of the SSA-MNPs showed that
ticles (SSA-MNPs) were prepared by a simple one-step
the cubic structure of the magnetite was well preserved af-
procedure through direct reaction of chlorosulfonic acid
ter introduction of the silica and sulfuric acid functional-
with silica-coated magnetite (Fe3O4) MNPs. The silica-
ity.24 The intensity of the 35.7° reflection of the SSA-
coated MNPs were prepared by modifying the surfaces of
MNPs was decreased after introduction of the sulfuric
the magnetite nanoparticles with negatively charged ci-
acid group.
trate groups, then coating with silica by reaction with tet-
The SSA-MNPs showed a high catalytic activity and
raethyl orthosilicate.
could be recovered and recycled several times without
The Fourier-transform IR spectra of the bare MNPs, ci-
significant loss of activity. In conclusion, we prepared
trate-functionalized MNPs, silica-coated MNPs, and
magnetically recyclable sulfuric acid functionalized silica
SSA-MNPs all showed peaks at 3300, 561, and 578 cm–1,
magnetic nanoparticles (SSA-MNPs) and examined their
which are assigned to –OH groups and Fe–O groups, re-
catalytic activity. The SSA-MNPs were prepared by a
spectively. Absorptions at 1558 and 1396 cm–1 were as-
simple procedure through direct functionalization of sili-
signed to binding of citric acid to the iron oxide
ca-coated iron(III) oxide nanoparticles with chlorosulfon-
nanoparticle surfaces.23 Peaks at 1091 and 1087 cm–1 cor-
ic acid. The SSA-MNPs are nontoxic, can be dispersed in
responded to the Si–O stretch, and the peak at 945 cm–1
various solvents, and can be readily recovered by using a
corresponded to the Si–OH stretch in the amorphous silica
magnet. In the condensation reaction of 6-amino-1,3-di-
shell. The formation of SSA-MNPs was confirmed by the
methyluracil with aldehydes, the SSA-MNP catalysts
presence of SO2 peaks at 1039 and 1138 cm–1. In addition,
gave a short reaction time coupled with a simple reaction
the intensity of the peak corresponding to the Fe–O group
procedure; the use of SSA-MNPs as inexpensive and re-
in SSA-MNPs decreased and a broad bond corresponding
Synthesis 2013, 45, 3300–3304
© Georg Thieme Verlag Stuttgart · New York

PAPER
Mono-, Di- and Tri[bis(6-aminopyrimidinyl)methanes]
3303
1H NMR (300 MHz, DMSO-d6): δ = 3.33 (s, 6 H, N–CH3), 3.36 (s,
6 H, N–CH3), 5.49 (s, 1 H, CHmethine), 6.97 (br s, 2 H, NH2), 7.28 (d,
J = 8.4 Hz, 1 H, Harom), 7.34 (d, J = 8.4 Hz, 1 H, Harom), 7.43 (s, 1 H,
usable catalysts make this method one of the most
efficient for the synthesis of bis(6-aminopyrimidi-
nyl)methanes.
Harom), 7.48 (br s, 2 H, NH2).
MS (EI, 70 eV): m/z = 466 [M+].
All reagents were of the best available purity and were used without
further purification. Fe3O4 nanoparticles (MNP), citric acid modi-
fied nanoparticles (CMNPs), and silica-coated magnetic nanoparti-
cles (Fe3O4/SiO2 MNPs) were prepared according to the literature
procedure.25 Trialdehydes 2g–i were prepared according to the lit-
erature procedure.26 The products 3a and 3c are known compounds
and their structures were deduced by comparison of their physical
and spectroscopic data (IR and 1H NMR) with previously reported
values.15 New products were characterized by elemental analysis
and by IR, 1H NMR, and 13C NMR spectroscopy. Fourier-transform
IR spectra were recorded on a Unicom Galaxy Series FTIR 5000
Anal. Calcd for C19H20Cl2N6O4: C, 48.83; H, 4.31; Cl, 15.17; N,
17.98. Found: C, 48.97; H, 4.44; Cl, 15.06; N, 18.11.
5,5′,5′′,5′′′-[1,4-Phenylenedi(methanetriyl)]tetrakis[6-amino-
1,3-dimethylpyrimidine-2,4(1H,3H)-dione] (3e)
White solid; yield: 595 mg (83%); mp >300 °C
IR (KBr): 3396, 3167, 2953, 1666, 1608, 1589, 1494 cm–1.
1H NMR (300 MHz, DMSO-d6): δ = 3.31 (s, 12 H, N–CH3), 3.34 (s,
12 H, N–CH3), 5.53 (s, 2 H, CHmethine), 6.90 (s, 4 H, Harom), 7.33 (br
s, 4 H, NH2), 7.56 (br s, 4 H, NH2).
1
spectrophotometer. H and 13C NMR spectra were recorded on a
MS (EI, 70 eV)): m/z = 718 [M+].
Bruker Avance 300 spectrometer at 300 and 75 MHz, respectively.
Chemical shifts (δ) are reported relative to TMS as an internal stan-
dard. Mass spectra were recorded on a Shimadzu QP 1100 EX mass
spectrometer operated in the EI mode. Elemental analyses were car-
ried out on a Vario EL III elemental analyzer. Sonication was per-
formed in a Struers Metason 200 HT ultrasonic cleaner with a
frequency of 50–60 Hz and an output power of 140 W.
Anal. Calcd for C32H38N12O8: C, 53.48; H, 5.33; N, 23.39. Found:
C, 53.35; H, 5.21; N, 23.44.
5,5′,5′′,5′′′-[1,3-Phenylenedi(methanetriyl)]tetrakis[6-amino-
1,3-dimethylpyrimidine-2,4(1H,3H)-dione] (3f)
White solid; yield: 574 mg (80%); mp 284–286 °C.
IR (KBr): 3454, 3360, 3111, 2962, 1683, 1601, 1496 cm–1.
1H NMR (300 MHz, DMSO-d6): δ = 3.33 (s, 12 H, N–CH3), 3.35 (s,
12 H, N–CH3), 5.52 (s, 2 H, CHmethine), 6.74 (s, 1 H, Harom), 6.81 (d,
J = 7.7 Hz, 2 H, Harom), 7.02 (t, J = 7.5 Hz, 1 H, Harom), 7.31 (br s, 4
H, NH2), 7.56 (br s, 4 H, NH2).
13C NMR spectra of products 3e, 3g, and 3i are not reported because
these compounds were insoluble in common organic solvents.
Sulfuric Acid Functionalized Silica-Coated Magnetic Nanopar-
ticles (SSA-MNPs)
Silica-coated magnetic nanoparticles (1 g) were added to a two-
necked flask fitted with a constant-pressure dropping funnel and a
tube to remove the HCl gas that formed, by conducting it to an ad-
sorbent solution. ClSO3H (1.5 mL) was added dropwise over 30
min at r.t. and the mixture was mechanically stirring slowly. HCl
gas immediately evolved, and the mixture was shaken well for 30
min. The resulting SSA-MNPs were washed with acetone (10 mL)
and distilled H2O (20 mL) to remove excess ClSO3H and finally
dried in an oven at 60 °C for 6 h.
13C NMR (75 MHz, DMSO-d6): δ = 28.0, 28.6, 29.9, 30.4, 35.7,
85.4, 87.1, 123.9, 127.7, 139.0, 150.7, 153.9, 155.1, 162.4, 164.0.
Anal. Calcd for C32H38N12O8: C, 53.48; H, 5.33; N, 23.39. Found:
C, 53.55; H, 5.40; N, 23.28.
5,5′,5′′,5′′′,5′′′′,5′′′′′-{1,3,5-Triazine-2,4,6-triyltris[oxy(3-
methoxy-5-nitro-4,1-phenylene)methanetriyl]}hexakis(6-ami-
no-1,3-dimethylpyrimidine-2,4(1H,3H)-dione) (3g)
Pale-yellow solid; yield: 1310 mg (85%); mp 265–268 °C.
Di- and Tri[bis(6-aminopyrimidinyl)methanes] 3e–i; General
Procedure
IR (KBr): 3398, 3119, 2953, 1691, 1614, 1537, 1498, 1452, 1344
cm–1.
A mixture of dialdehyde 2e–f or trialdehyde 2g–i (1 mmol), 6-ami-
no-1,3-dimethyluracil (5 mmol for 2e–f or 7 mmol for 2g–i) and
SSA-MNPs (0.1 g) in EtOH (8 mL) was irradiated with ultrasound
(50–60 Hz, 140 W) at 50 °C for an appropriate time (see Table 2).
When the reaction was complete (TLC), the SSA-MNPs were re-
moved by using an external magnetic field. The solution was then
concentrated and left to evaporate slowly. H2O–EtOH (5:1; 30 mL)
was added and the resulting solid products were collected by filtra-
tion, washed with H2O–EtOH (5:1, 30 mL) to remove excess 6-ami-
no-1,3-dimethyluracil.
1H NMR (300 MHz, DMSO-d6): δ = 3.34 (s, 36 H, N–CH3), 3.75 (s,
9 H, O–CH3), 5.66 (s, 3 H, CHmethine), 7.25 (s, 3 H, Harom), 7.39 (s, 3
H, Harom), 7.2–7.9 (br s, 12 H, NH2).
Anal. Calcd for C60H63N21O15: C, 54.67; H, 4.82; N, 22.31. Found:
C, 54.75; H, 4.90; N, 22.22.
5,5′,5′′,5′′′,5′′′′,5′′′′′-[1,3,5-Triazine-2,4,6-triyltris(oxy-4,1-
phenylenemethanetriyl)]hexakis[6-amino-1,3-dimethylpyrimi-
dine-2,4(1H,3H)-dione](3h)
White solid; yield: 1160 mg (88%); mp 285–288 °C.
5,5′-[(3-Nitrophenyl)methylene]bis[6-amino-1,3-dimethyl-
pyrimidine-2,4(1H,3H)-dione] (3b)
IR (KBr): 3377, 3119, 2953, 2829, 1689, 1606, 1562, 1496, 1456
cm–1.
1H NMR (300 MHz, DMSO-d6): δ = 3.30 (s, 18 H, N–CH3), 3.33 (s,
18 H, N–CH3), 5.61 (s, 3 H, CHmethine), 6.92–7.02 (m, 9 H, Harom),
7.25 (t, J = 7.8 Hz, 3 H, Harom), 7.34 (br s, 12 H, NH2).
13C NMR (75 MHz, DMSO-d6): δ = 28.7, 30.4, 35.7, 85.2, 118.7,
119.8, 124.7, 129.1, 142.5, 150.9, 151.7, 153.9, 164.1, 173.4.
White solid; yield: 398 mg (90%); mp 248–250 °C.
IR (KBr): 3352, 3119, 2955, 2831, 1689, 1662, 1606, 1591, 1502,
1344 cm–1.
1H NMR (300 MHz, DMSO-d6): δ = 3.34 (s, 6 H, N–CH3), 3.36 (s,
6 H, N–CH3), 5.66 (s, 1 H, CHmethine), 7.30 (br s, 2 H, NH2), 7.51 (t,
J = 7.8 Hz, 2 H, Harom), 7.59 (d, J = 7.6 Hz, 1 H, Harom), 7.86 (s, 2 H,
NH2), 7.99 (d, J = 7.8 Hz, 1 H, Harom).
Anal. Calcd for C60H63N21O15: C, 54.67; H, 4.82; N, 22.31. Found:
C, 54.50; H, 4.88; N, 22.43.
Anal. Calcd for C19H21N7O6: C, 51.47; H, 4.77; N, 22.11. Found: C,
51.22; H, 4.69; N, 22.34.
5,5′,5′′,5′′′,5′′′′,5′′′′′-[1,3,5-Triazine-2,4,6-triyltris(oxy-3,1-
phenylenemethanetriyl)]hexakis[6-amino-1,3-dimethylpyrimi-
dine-2,4(1H,3H)-dione](3i)
5,5′-[(2,4-Dichlorophenyl)methylene]bis[6-amino-1,3-dimeth-
ylpyrimidine-2,4(1H,3H)-dione] (3d)
White solid; yield: 407 mg (87%); mp 275–277 °C.
IR (KBr): 3358, 3159, 3049, 2955, 1689, 1678, 1595, 1500 cm–1.
White solid; yield: 1146 mg (87%); mp 291–294 °C.
IR (KBr): 3379, 3130, 2955, 2810, 1687, 1610, 1564, 1500, 1456
cm–1.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 3300–3304

3304
A. R. Karimi et al.
PAPER
1H NMR (300 MHz, DMSO-d6): δ = 3.29 (s, 18 H, N–CH3), 3.33 (s,
18 H, N–CH3), 5.59 (s, 3 H, CHmethine), 7.06 (d, J = 8.4 Hz, 6 H,
(10) (a) Zhi, C.; Long, Z.-Y.; Gambino, J.; Xu, W.-C.; Brown, N.
C.; Barnes, M.; Butler, M.; LaMarr, W.; Wright, G. E.
J. Med. Chem. 2003, 46, 2731. (b) Devi, I.; Bhuyan, P. J.
Tetrahedron Lett. 2005, 46, 5727.
(11) (a) Kappe, C. O. Tetrahedron 1993, 49, 6937. (b) Ibrahim,
D. A.; El-Metwally, A. M. Eur. J. Med. Chem. 2010, 45,
1158. (c) Deshmukh, M. B.; Salunkhe, S. M.; Patil, D. R.;
Anbhule, P. V. Eur. J. Med. Chem. 2009, 44, 2651.
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6114.
Harom), 7.16 (d, J = 8.4 Hz, 6 H, Harom), 7.45 (br s, 12 H, NH2).
Anal. Calcd for C63H66N24O24: C, 49.03; H, 4.31; N, 21.78. Found:
C, 48.90; H, 4.40; N, 21.90.
Acknowledgment
We gratefully acknowledge financial support from the Research
Council of Arak University.
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Lett. 2003, 44, 9181.
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M.; Stelzner, A.; Wutzlerc, P.; Schmidtke, M. Bioorg. Med.
Chem. Lett. 2005, 15, 37.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnuIomprifgtooatrinSugpIoi
n
nfomartit
(15) Azizian, J.; Mohammadizadeh, M. R.; Teimouri, F.;
Mohammadi, A. A.; Karimi, A. R. Synth. Commun. 2006,
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Rorison, J. M.; Weaver, M. S. US 6437123, 2002.
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Synthesis 2013, 45, 3300–3304
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