Synthesis of pyrano[2,3‐d]pyrimidines and pyrido[2,3‐d]pyrimidines in the magnetized deionized water based on UV–visible study

Article abstract of DOI:10.1007/s13738-020-02073-z

Abstract: A green synthetic route to the facile one-pot multicomponent synthesis of pyrano[2,3‐d]pyrimidines and pyrido[2,3‐d]pyrimidines have been developed using magnetized deionized water (MDW) as a green solvent under catalyst-free conditions. All rea

Full text of DOI:10.1007/s13738-020-02073-z

Journal of the Iranian Chemical Society
https://doi.org/10.1007/s13738-020-02073-z
ORIGINAL PAPER
Synthesis of pyrano[2,3‐d]pyrimidines and pyrido[2,3‐d]pyrimidines
in the magnetized deionized water based on UV–visible study
Mohammad Bakherad1 · Ghadamali Bagherian1 · Amin Rezaeifard1 · Fatemeh Mosayebi1 · Behzad Shokoohi1 ·
Ali Keivanloo1
Received: 14 May 2020 / Accepted: 21 September 2020
© Iranian Chemical Society 2020
Abstract
A green synthetic route to the facile one-pot multicomponent synthesis of pyrano[2,3‐d]pyrimidines and pyrido[2,3‐d]pyri-
midines have been developed using magnetized deionized water (MDW) as a green solvent under catalyst-free conditions.
All reactions carried out in a short period of time and the products are obtained in high-to-excellent yields. The developed
synthetic technique ofers numerous advantages including eco-friendly, clean synthesis, simplicity, low cost, short reaction
times, high reaction yields, and easy workup compared to the traditional synthetic method. Moreover, the reaction rates were
followed spectrophotometrically by monitoring the changes in the absorption spectrum of the reaction mixture in ordinary
deionized water and MDW.
Graphic abstract
O
O
N
R
O
N
N
N
+
O
NH4OAc
CN
N
R
O
O
O
CN
ArCHO
O
Ar
O
N
Ar
O
R
CN
CN
N
O
N
R
N
H
NH2
NH2
O
N
O
N
Ar
CN
NH2
N
N
O
NH2
O
N
H
Keywords Catalyst-free · Pyrano[2,3‐d]pyrimidines · Pyrido[2,3‐d]pyrimidines · MDW
Electronic supplementary material The online version of this
article (https://doi.org/10.1007/s13738-020-02073-z) contains
supplementary material, which is available to authorized users.
Extended author information available on the last page of the article
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Journal of the Iranian Chemical Society
been reported for the synthesis of pyrano[2,3‐d]pyrimidine
[20–23] and pyrido[2,3-d]pyrimidine [24–31] derivatives
using various catalysts. These techniques, however, sufer
from some drawbacks such as using expensive reagents and
catalysts, toxic reagents and solvents, strong basic or acidic
conditions, strict reaction conditions, tedious workup, and
extended reaction times, or low product yields. Moreover,
our literature study indicated that there is only one report rel-
evant to the synthesis of pyrido[2,3-d]pyrimidines using the
multicomponent reaction of aromatic aldehydes, barbituric
acids, malononitrile, and ammonium acetate. Jonnalagadda
et al. [32] have reported a four-component reaction of malo-
nonitrile, an aldehyde, dimethyl barbituric acid, and ammo-
nium acetate in the presence of CeO2-doped hydroxyapatite
(CeO2/HAp) as a catalyst for the synthesis of pyrido[2,3-d]
pyrimidines in EtOH at room temperature. Considering the
above subjects and based on our research works on the use
of MDW as a solvent in organic synthesis [33–37], herein we
report a catalyst-free, green, and clean method for the one-
pot synthesis of pyrano[2,3‐d]pyrimidines and pyrido[2,3‐d]
pyrimidines in MDW (Scheme 1).
Introduction
Organic synthesis in green solvents is attractive, particu-
larly from the standpoint of green chemistry. The green
synthesis is important because of reducing by-products and
waste chemicals. The use of water represents economically
and environmentally viable alternatives to organic solvents.
Moreover, it would be cheap, non-toxic, very safe, and
eco-friendly in comparison with the organic solvents [1].
Unfortunately, most organic synthesis cannot be carried out
with water as a solvent, because it requires the presence of
additives and catalysts. The water magnetization is an easy
method without excessive energy consumption when a con-
stant foreign magnet is used. Such a magnet can be installed
on a previously established water tube system, resulting in
no additional energy required for water magnetization [2–4].
Multicomponent reactions (MCRs) have become very
important in modern organic chemistry [5]. Unlike the step-
by-step reactions, MCRs provide a convenient synthetic
method to generate products of one-step structural complex-
ity and minimize waste as the number of reagents, solvents,
and adsorbents are signifcantly reduced. Therefore, MCRs
rely on an eco-friendly green synthetic methodology [6–8].
Heterocyclic motifs such as pyrano[2,3‐d]pyrimidines and
pyrido[2,3‐d]pyrimidines have a broad range of applications.
Pyrano[2,3-d]pyrimidines exhibit anti-bronchitis, hepatopro-
tective, anti-AIDS, and anti-tumor activities [9–13]. Also,
pyrido[2,3-d]pyrimidines are nitrogen-containing hetero-
cyclic molecules with a wide range of biological activities
include anti-convulsant [14], anti-microbial [15], anticancer
[16], anti-infammatory [17], antimalarial [18], and antivi-
ral activities [19]. Therefore, major research attention has
been devoted to the synthesis of such heterocyclic com-
pounds. In recent years, several new efcient methods have
.
Results and discussion
The MDW was prepared according to previously reported
[37]. The deionized water (5 mL) was put in a test tube,
which was then put in a magnetic feld (0.8 T) at diferent
times. The tube was subsequently removed from the instru-
ment and used for the reaction (Fig. 1).
To evaluate the virtue of MDW in the catalyst-free syn-
thesis of pyrano[2,3‐d]pyrimidines, initially, pilot studies
Scheme 1 Synthesis of
pyrano[2,3‐d]pyrimidines and
pyrido[2,3-d]pyrimidines in
MDW
O
O
N
R
O
N
+
O
CN
NH4OAc
N
R
O
O
N
O
CN
ArCHO
O
Ar
O
Ar
CN
R
CN
N
N
N
O
NH2
O
N
R
N
NH2
H
O
N
O
N
Ar
CN
NH2
N
N
O
NH2
O
N
H
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Journal of the Iranian Chemical Society
Table 1 Efects of diferent solvents on the reaction of dimethyl bar-
were carried out with a model reaction between dimethyl
barbituric acid (1a) benzaldehyde (2a), and malononitrile
(3) under diferent conditions. In the primary study, the reac-
tion was investigated under various solvents. As shown in
Table 1, the reaction was performed in various non-polar
solvents such as toluene and 1,4-dioxane; a perusal of the
results shows that there were no reaction yields (Table 1,
entries 1, 2). Reactions conducted in polar solvents such as
DMF, CH3CN, THF, CHCl3, ethyl acetate EtOH, MeOH,
and H2O gave low yields (Table 1, entries 3–10). Surpris-
ingly, the product (4a) was obtained in a 97% yield within
the same time (70 min) when MDW was used as the solvent
(Table 1, entry 11). In view of the green nature, short reac-
tion time, and excellent yields, MDW was demonstrated to
be the perfect solvent for the present procedure. As indicated
in Table 1, the highest reaction yield was obtained when
MDW was used as the solvent (Table 1, entry 11). Then, the
model reaction was investigated in MDW under diferent
reaction conditions. As shown in Table 2, an increase in the
water magnetization time up to 15 min led to a high reac-
tion yield (97%) (Table 2, entry 3). Also in the optimization
process, the role of temperature was investigated (Table 2,
entries 5 and 6). We fnd that 70 °C gives the best result
(Table 2, entry 3). Moreover, increasing the reaction time
did not change product yield (Table 2, entry 7).
bituric acid, benzaldehyde, and malononitrile
O
O
Ph
CN
CN
CN
Solvent
N
N
+
Ph-CHO
+
Catalyst-free
O
N
O
O
N
O
NH2
(
1a
)
(
2a
)
(3
)
(4a
)
Entrya
Solvent
Temp. (°C)
Yield (%)b
1
2
3
4
5
6
7
8
1,4-dioxane
Toluene
DMF
CH3CN
THF
CHCl3
Ethyl acetate
EtOH
100
100
90
80
65
60
75
75
60
70
70
–
–
10
12
15
10
13
18
20
23
97
9
10
11
MeOH
H2O
MDWc
aReaction conditions: dimethyl barbituric acid (1a) (1.0 mmol), ben-
zaldehyde (2a) (1.0 mmol), malononitrile (3) (1.0 mmol), solvent
(5 mL) for 70 min
bIsolated yield
With the optimal reaction conditions in hand, we illus-
trated the scope of aromatic aldehydes with diferent sub-
stituents and the signifcance of MDW as a solvent during
the multicomponent process by the yields of the reac-
tions (Table 3). As indicated in Table 3, both the aromatic
aldehydes having electron-donating (Table 3, entries 2
and 3) and electron-withdrawing (Table 3, entries 11–14)
cMagnetization time 15 min
Table 2 Synthesis of pyrano[2,3‐d]pyrimidine (4a) in MDW under
various reaction conditions
Entrya
Magnetization
time (min)
Temp. (°C)
Time (min)
Yield (%)b
1
2
3
4
5
6
7
5
10
15
20
15
15
15
70
70
70
70
90
50
70
70
70
70
70
70
120
120
70
84
97
96
60
43
97
Fig. 1 The pilot for solvent
magnetization apparatus
aReaction conditions: dimethyl barbituric acid (1a) (1.0 mmol), ben-
zaldehyde (2a) (1.0 mmol), malononitrile (3) (1.0 mmol), MDW
(5 mL)
bIsolated yield
substituents on their aromatic ring provided the related prod-
ucts in high yields. Under the same reaction conditions, aro-
matic aldehydes with a halogen group on the benzene ring
gave good isolated yields of the corresponding pyrano[2,3‐
d]pyrimidines (4) (Table 3, entries 4–9). On the other hand,
aromatic aldehydes with an electron-withdrawing group on
the benzene ring were carried out at shorter reaction times.
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Journal of the Iranian Chemical Society
Table 3 Synthesis of pyrano[2,3‐d]pyrimidines(4)
O
N
Ar
O
O
MDW, 70 o
C
CN
CN
CN
N
N
Ar-CHO
+
O
+
Catalyst-free
O
NH2
(4)
O
N
(
1)
(
2)
(
3
)
Entrya
Ar
Reaction time (min)
Product
Yield (%)b
MP (°C) (Lit) [Ref.]
1
2
3
4
5
6
7
8
Ph
70
90
100
65
70
65
65
70
65
80
45
45
60
50
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
97
90
92
87
91
82
89
92
97
85
95
95
90
97
240–242 (237–239) [38]
221–223 (222–224) [38]
280–282 (281–283) [38]
229–231 (226–228) [38]
271–273 (270–272) [38]
224–226 (223–225) [38]
209–211 (210–212) [38]
227–229 (229–231) [38]
225–227 (228–230) [38]
251–253 (250–252) [39]
224–226
2-MeO–C6H4–
4-MeO–C6H4–
2-Br–C6H4–
3-Br–C6H4–
3-Cl–C6H4–
4-Cl–C6H4–
3-F–C6H4–
9
4-F–C6H4–
10
11
12
13
14
2,4-Cl2–C6H3–
4-CN–C6H4–
2-NO2–C6H4–
3-NO2–C6H4–
4-NO2–C6H4–
241–243
205–207 (207–209) [38]
212–214 (214–216) [38]
aReaction conditions: 1,3-dimethyl barbituric acid (1a) (1.0 mmol), an aldehyde (2) (1.0 mmol), malononitrile (3) (1.0 mmol), MDW (5 mL),
magnetization time (15 min), 70 οC
bIsolated yield
Therefore, this investigation indicated MDW was efective
for the synthesis of pyrano[2,3‐d]pyrimidines (4) with high
yields and short reaction times.
Table 4 The efect of diferent magnetized/non-magnetized solvents
on the synthesis of 6e
Entrya
Solvent
Temp. (°C)
Yield (%)b
Yield (%)b
Non-magnet- Magnetized
ized
Our extensive literature survey showed that despite
the potent biological activities of pyrido[2,3-d]pyrimi-
dines, there are few reports devoted to the preparation of
pyrido[2,3-d]pyrimidines [24–28]. However, a literature
survey showed no reports on the catalyst-free synthesis of
pyrido[2,3-d]pyrimidines (6) via a four-component reaction
of aromatic aldehydes, barbituric acids, malononitrile, and
ammonium acetate in MDW.
1
2
3
4
5
6
7
8
9
Toluene
DMF
CH3CN
THF
CHCl3
Ethyl acetate
EtOH
MeOH
H2O
100
100
80
65
60
75
78
64
90
20
50
20
10
30
35
42
40
44
23
75
25
20
44
55
80
66
95
To prove the efcacy of magnetized water in the synthesis
of pyrido[2,3-d] pyrimidines (6), initially, the catalyst-free
reaction of model reaction between dimethyl barbituric acid
(1a) 2,6-dichloro benzaldehyde (2e), malononitrile (3), and
ammonium acetate (5), as a model reaction was carried out
in the magnetized and non-magnetized solvents (Table 4).
As indicated in Table 4, the results obtained showed that the
efciency and yield of the reaction in MDW were higher
than those obtained in solvents like toluene, DMF, CH3CN,
THF, CHCl3, ethyl acetate, ethanol, and methanol, in the
absence of any catalyst or additive (Table 4, entry 9). To
illustrate the versatility of this method, a series of aromatic
aldehydes were studied under the standardized reaction con-
ditions, and the results obtained are given in Table 5.
aReaction conditions: dimethyl barbituric acid (1a) (1.0 mmol),
2,6-dichloro benzaldehyde (2e) (1.0 mmol), malononitrile (3)
(1.0 mmol), ammonium acetate (5), solvent (5 mL), magnetization
time (15 min), for 70 min
bIsolated yield
As presented in Table 5, 4-methoxy benzaldehyde reacted
with dimethyl barbituric acid (1a), malononitrile (3), and
ammonium acetate to give the corresponding product
under catalyst-free conditions in high yield (90%) at 60 min
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Journal of the Iranian Chemical Society
Table 5 Synthesis of pyrido[2,3-d]pyrimidines (6)
O
O
Ar
R
N
R
O
CN
MDW, 90 oC
Catalyst-free
CN
CN
N
ArCHO
+
O
+
+
NH4OAc
O
N
R
N
R
N
H
NH2
(
1
)
(2
)
(3
)
(5
)
(6)
Entrya
R
Ar
Reaction time
(min)
Product
Yield (%)b
MP(°C) (Lit)[ref.]
1
2
3
4
5
6
7
8
Me
Me
Me
Me
Me
Me
Me
Me
Me
H
4-MeO–C6H4–
2-Br–C6H4–
3-Br–C6H4–
60
70
70
90
80
80
50
90
45
60
50
6a
6b
6c
6d
6e
6f
6g
6h
6i
90
92
96
87
95
90
92
85
97
80
85
224–226 (220–222) [32]
203–205 (201–203) [32]
234–236
260–262
271–273
205–207 (203–205) [32]
256–258
242–244 (242–243) [32]
228–230
>300 (>300) [40]
262–264
2,4-Cl2–C6H3–
2,6-Cl2–C6H3–
3-F–C6H4–
2-NO2–C6H4–
3-NO2–C6H4–
4-NO2–C6H4–
2,4-Cl2–C6H3–
2,6-Cl2–C6H3–
9
10
11
6j
6k
H
aReaction conditions: barbituric acid (1) (1.0 mmol), an aldehyde (2) (1.0 mmol), malononitrile (3) (1.0 mmol), ammonium acetate (5)
(2.0 mmol), magnetization time (15 min), MDW (5 mL), 90 °C
bIsolated yield
(Table 5, entry 1), whereas Jonnalagadda et al. [32] reported
that this transformation could not be accomplished in the
absence of a catalyst even after 12 h refuxing EtOH. Moreo-
ver, a sterically hindered aldehyde such as 2,6-dichloroben-
zaldeyhed aforded the desired pyrido[2,3-d] pyrimidines in
high yield (Table 5, entries 6 and 12). Also, the reaction time
of aromatic aldehydes bearing electron-withdrawing groups
such as 4-nitrobenzaldehyde (Table 5, entry 10) was rather
shorter than that of other aldehydes.
Pyrido[2,3-d] pyrimidines (6a–k) were confrmed by
their 1H NMR, 13C NMR, and analytical data. The 1H NMR
spectrum for (6b) shows a singlet for the CH3 protons at δ
3.06, a singlet for the CH3 protons at δ 3.37, a singlet for
the methine proton (CH) at δ 4.87, two multiplets for the
aromatic ring protons at δ 7.10–7.30, a singlet for the NH2
group at δ 7.36, and a doublet for the aromatic ring protons
at 7.54 (Scheme 2).
Toledo et al. [41] have demonstrated the efect of an exte-
rior magnetic feld on the physical and chemical properties
of water via a theoretical and an experimental method. They
have explained that competition among the intra- and inter-
molecular hydrogen bond lattices in water, which dimin-
ish the powerful intra-cluster hydrogen bonds, breaks the
big clusters and forms the smaller ones with stronger inter-
cluster hydrogen bonds. Thus, there are a number of hydro-
gen bonds between the MDW molecules and the reacting
molecules enhancement. Also, very recently, we described
the synthesis of 9-substituted-9H-diuracilopyrans from the
reaction of barbituric acids with aldehydes in MDW as a sol-
vent [42]. Based on the obtained results, we proved that the
MDW causes more attractive forces between the aldehydes
and barbituric acid molecules and, hence, enhances the inter-
actions between them, leading to an increase in the reaction
rate and chemical reactivity at the molecular level. Thus we
The obtained results have revealed the applicability of
MDW as a promoting medium for catalyst-free synthesis of
pyrido[2,3-d]pyrimidines. Encouraged by these promising
results, we studied the reaction of 6-aminouracile (7), aro-
matic aldehydes (2) and malononitrile (3) at 80 °C in MDW.
In the literature, this reaction was widely studied; however,
literature search showed the synthesis of pyrido[2,3-d]
pyrimidine derivatives (6) using 6-aminouracile in the
presence of KF/Al2O3[27], l-proline [28], MgO [29], tri-
ethyl benzyl ammonium chloride [30], and piperidine [31]
as catalysts. It was very interesting to fnd that the reaction
between 6-aminouracile, malononitrile, and aromatic alde-
hydes containing electron-donating or electron-withdrawing
proceeded well in the none-catalyst MDW, and the desired
products were obtained in 86–95% yield (Table 6).
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Journal of the Iranian Chemical Society
Table 6 The reaction of 4-aminouracile (7), aldehydes (2), and malononitrile (3)
O
O
Ar
MDW, 90 o
CN
C
CN
HN
HN
Ar-CHO
+
NH2
+
Catalyst-free
CN
O
N
H
O
N
H
N
H
NH2
(
7
)
(2
)
(
3
)
(6)
Entrya
Ar
Reaction time (min)
Productb
Yield (%)c
MP(°C) (Lit)[ref.]
1
2
3
4
5
6
7
Ph
120
120
120
130
110
90
6l
94
89
90
92
86
88
94
>300 (>300) [40]
>300 (>300) [40]
>300 (>300) [40]
>300 (>300) [40]
>300 (>300) [40]
>300 (>300) [40]
>300 (>300) [40]
4-MeO–C6H4–
4-Me–C6H4–
3-OH–C6H4–
2-Cl–C6H4–
2,4–Cl2–C6H3–
3-NO2–C6H4–
6m
6n
6o
6p
6i
90
6q
aReaction conditions: 4-aminouracile (7) (1.0 mmol), an aldehyde (2) (1.0 mmol), malononitrile (3) (1.0 mmol), magnetization time (15 min),
MDW (5 mL), 80 °C
bMelting points,>300 °C
cIsolated yield
H
H
O
H
H
O
H
O
N
O
O
H
N
O
O
N
N
O
H
O
(1a)
(I)
H
H
H
O
H
H
O
H
H
H
H
H
H
O
O
H
H
+
O
O
H
H
CN
CN
H
O
HO
CN
H
Ar
NC
CN
Ar
H
-H2O
Ar
CN
(II)
O
Ar
H
CN
N
O
N
O
N
H
H
NH4OAc
H
H
O
O
O
(III)
H
H
O
N
Ar
O
Ar
O
O
N
Ar
O
O
N
Ar
O
O
Ar
O
N
Ar
H
H
H
H
CN
CN
H
CN
CN
NH
CN
NH
CN
NH2
N
N
N
N
N
CN
NH2
O
N
O
N
O
NH2
O
O
N
N
H
O
N
H
N
H
O
O
O
H
H
H
H
H
O
H
(
6
)
(
IV
)
(4)
Scheme 2 A plausible mechanism for synthesis of pyrano[2,3‐d]pyrimidine (4a)
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Journal of the Iranian Chemical Society
2
1.5
1
CN
CN
CN
Ph
H
a
b
c
Ph-CHO
(2a)
+
CN
(3)
(I)
O
N
Ph
O
O
CN
CN
CN
Ph
H
N
N
+
0.5
0
O
NH2
O
N
O
(I)
(1a)
(4a)
220
240
260
280
300
320
340
360
380
wavelenght(nm)
Scheme 3 Synthesis of benzylidene malononitrile (I) and
pyrano[2,3‐d]pyrimidine (4a)
Fig. 2 Absorption spectra of aqueous solutions of benzaldehyde (a)
(0.00016 M), malononitrile (b) (0.00018 M), and benzylidenmalon-
onitrile (c) (0.00009 M) against water as the blank
believe that the hydrogen bonds between molecules of MDW
and molecules of the substrates and intermediates involved
in a reaction are responsible for the reaction activation.
Mechanistically, dimethyl barbituric acid (1a) was converted
to compound (I) in the presence of MDW. Also, aryliden-
emalononitrile (II) was formed from the Knoevenagel con-
densation of aryl aldehyde (2) with the highly active CH
acidic malononitrile (3). In the next step, the MDW-facili-
tated Michel addition reaction between enolate form (II) and
arylidenemalononitrile (II) forms an intermediate. Finally,
the transient intermediate (III) undergoes cyclization, and
tautomerization yielded pyrano[2,3‐d]pyrimidines (4). On
the other hand, the reaction between intermediate (III) and
ammonium acetate forms an intermediate (IV), which is
then cyclized to aford the aromatized product (6).
Fig. 3 The molar absorptivities of benzaldehyde (a), malononitrile
(b), and benzylidenmalononitrile (c) in water as the solvent
UV–visible study
of 220–380 nm (ε=1—16 L mol−1 cm−1). This fgure also
shows that benzylidene malononitrile (I) has three absorp-
tion peaks at 228 nm (ε=6.6×103 L mol−1 cm−1), 249 nm
(ε = 5.7 × 103 L mol−1 cm−1), and 308 nm (ε = 1.44 × 104
L mol−1 cm−1), with a shoulder at 224 nm (ε = 6.4 × 103
L mol−1 cm−1). Figure 3 shows the molar absorptivity of
these materials. This fgure shows that malononitrile (3) and
benzaldehyde (2a) do not absorb at 308 nm. Accordingly,
at 308 nm, only benzylidene malononitrile (I) absorbs, and
an increase in absorption at this wavelength indicates the
formation of benzildine malononitrile intermediate (I) as
the product.
To prove the efectiveness of the MDW on the synthesis of
pyrano[2,3‐d]pyrimidine (4a), the reaction of benzaldehyde
(2a) with malononitrile (3) in MDW and ODW has been
investigated by UV–visible spectroscopy methods. Fur-
thermore, the reaction of dimethyl barbituric acid (1a) with
benzylidene malononitrile (I) in MDW and ODW was also
studied (Scheme 3).
Spectra for benzaldehyde (2a), malononitrile (3),
and benzylidenmalononitrile (I)
The UV–visible spectra of pure solutions of benzalde-
hyde (2a), malononitrile (3), and benzylidene malononi-
trile (I) were recorded (Fig. 2). A portion of each solution
was transferred into a quartz cell. The spectra of the pre-
pared solutions against deionized water as the blank were
scanned over the range of 220–380 nm (Fig. 2). This fgure
shows that benzaldehyde has a maximum absorption at 248
(molar absorptivity=ε=1.14×104 L mol−1 cm−1), with a
shoulder at 286 nm (ε = 1.4 × 103 L mol−1 cm−1) and that
malononitrile (3) has a very low absorbance in the range
Investigating the rate of reaction between benzal‑
dehyde (2a) and malononitrile (3) in ODW and MDW
To study the efect of MDW on the rate of reaction between
benzaldehyde (2a) and malononitrile (3), the reaction rate
was studied in two states. The reaction rates in the frst state
in ODW and the second state in MDW were investigated.
The reaction rates were followed spectrophotometrically by
monitoring the changes in the absorption spectrum of the
1 3

Journal of the Iranian Chemical Society
2
1.8
1.6
1.4
1.2
1
30min Ordinary
30min Magneꢀzed
0min
2
1.8
1.6
1.4
1.2
1
6min
12min
20min
30min
45min
0.8
0.6
0.4
0.2
0
0.8
0.6
0.4
0.2
0
220
240
260
280
300
320
340
360
380
wavelength(nm)
220
270
320
wavelength(nm)
370
Fig. 4 The UV–visible spectra of the reaction mixture for the reac-
tion between benzaldehyde and malononitrile in ODW at 25 °C (at 0,
6, 12, 20, 30, and 45 min after the beginning of the reaction) against
water as the blank
Fig. 6 The UV–visible spectra of the reaction mixture for the reac-
tion between benzaldehyde and malononitrile in ODW and MDW at
30 min after the beginning of the reaction
2
ΔA Ordinary
ΔA Magneꢀzed
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
1.8
0min
1.6
6min
1.4
12min
1.2
20min
30min
45min
1
0.8
0.6
0.4
0.2
0
220
270
320
wavelength(nm)
370
0
10
20
30
40
50
Reacꢀon ꢀme (min)
Fig. 5 The UV–visible spectra of the reaction mixture for the reaction
between benzaldehyde and malononitrile in MDW at 25 °C (at 0, 6,
12, 20, and 30 min after the beginning of the reaction) against water
as the blank
Fig. 7 The absorption changes at the same time for ODW (a) and
MDW (b)
Table 7 Comparison of the benzylidene malononitrile (I) yields in
ODW and MDW
reaction mixture in the UV–visible region. To do this, the
absorption spectra of the reaction mixture in the UV–visible
region were recorded at diferent times after the beginning of
the reaction. Time was measured from just after the mixture
of the two solutions of benzaldehyde (2a) and malononitrile
(3). Figures 4 and 5 show the absorption spectra of the reac-
tion mixture in ODW and MDW, respectively. The higher
absorbance changes at 308 nm indicate a faster reaction rate
or a faster rate of intermediate formation (benzylidenmalo-
nonitrile). Comparison of the spectra in Figs. 4 and 5 shows
that the reaction rate in MDW is faster than that in ODW.
In Fig. 6, the recorded spectra at the same time (30 min)
show that the reaction rate in MDW is faster than that in
ODW.
Time (min) Compound (I) Compound (I) Yield
Yield (%)
in MDW
(mol L−1) in
ODW
(mol L−1) in
MDW
(%) in
ODW
6
3.84×10–6
6.85×10–6
9.43×10–6
1.65×10–5
2.81×10–5
4.50×10–6
1.18×10–5
1.49×10–5
3.19×10–5
4.07×10–5
2.4
4.3
5.9
10.3
17.5
2.8
7.4
9.3
19.9
25.4
12
20
30
45
The concentration of benzylidene malononitrile (I) was
obtained at the given times by the EXRSM method [43].
Table 7 shows the concentration of the produced benzylidene
malononitrile (I) and the reaction yield in ODW and MDW.
The results obtained show that the product formation rate in
MDW is greater than that in ODW.
Figure 7 shows the absorption changes at 308 nm at the
same time (ΔA = At − A0) in ODW and MDW. This fgure
shows that the absorption changes in MDW are greater than
those in ODW. In other words, the reaction rate in MDW is
faster than that in ODW.
1 3

Journal of the Iranian Chemical Society
3
2.5
2
35000
30000
25000
20000
15000
10000
5000
0
c
c
b
a
b
a
1.5
1
0.5
0
220
270
320
wavelength(nm)
370
220
270
320
wavelength(nm)
370
Fig. 8 Absorption spectra of aqueous solutions of benzylidenmalo-
nonitrile (a) (0.00009 M), dimethyl barbituric acid (b) (0.00018 M),
and pyrano[2,3‐d]pyrimidine (c) (0.000084 M) against an aqueous
solution of 50% methanol (v/v) as the blank
Fig. 9 The molar absorptivity of benzylidene malononitrile (a)
(0.00009 M), dimethyl barbituric acid (b) (0.00018 M), and
pyrano[2,3‐d]pyrimidine (c) (0.000084 M) in aqueous solution of
50% methanol (v/v) as the solvent
2.5
Spectra of dimethyl barbituric acid (1a), ben‑
zylidene malononitrile (I), and pyrano[2,3‐d]pyrimi‑
dine (4a)
1 min
7 min
13 min
19 min
25 min
31 min
37 min
43 min
49 min
2
1.5
1
The UV–visible spectra of pure solutions of dimethyl
barbituric acid (1a) benzylidene malononitrile (I), and
pyrano[2,3‐d]pyrimidine (4a) were recorded (Fig. 8). The
spectra of the prepared solutions against an aqueous solution
of 50% methanol (v/v) as the blank were scanned over the
range of 220–380 nm (Fig. 8). This fgure shows that dime-
thyl barbituric acid (1a) has two maximum absorptions at
225.5 nm (molar absorptivity=ε=6.1×103 L mol−1 cm−1)
and 258.5 nm (ε=7.3×103 L mol−1 cm−1). This fgure also
shows that benzylidene malononitrile (I) has three absorp-
tion peaks at 228 nm (ε=6.6×103 L mol−1 cm−1), 249 nm
(ε = 5.7 × 103 L mol−1 cm−1), and 308 nm (ε = 1.44 × 104
L mol−1 cm−1), with a shoulder at 224 nm (ε = 6.4 × 103
L mol−1 cm−1). This fgure also shows that pyrano[2,3‐d]
pyrimidine (4a) has two absorption peaks at 258.5 nm
(ε=1.34×104 L mol−1 cm−1) and 304.5 nm (ε=5.8×103 L
mol−1 cm−1). Figure 9 shows the molar absorptivity of these
materials. This fgure shows that dimethyl barbituric acid
(1a) does not absorb at 308 nm. Accordingly, at 308 nm, the
molar absorptivity of benzildine malononitrile (I) is more
than twice larger than that for pyrano[2,3‐d]pyrimidine (4a).
The decrease in absorption at this wavelength indicates the
formation of pyrano[2,3‐d]pyrimidine (4a) as the product.
The higher absorbance changes at 308 nm indicate a faster
reaction rate or a faster rate of product formation.
0.5
0
220
240
260
280
300
320
340
360
380
Wavelength(nm)
Fig. 10 The absorption spectra of the reaction mixture in ODW with
a scan time interval of 6 min against an aqueous solution of 50%
methanol (v/v) as the blank
Investigating the rate of reaction between dimethyl
barbituric acid (1a) and benzylidene malononitrile
(I) in ODW and MDW
To compare the effect of MDW on the rate of reaction
between dimethyl barbituric acid (1a) and benzylidene
malononitrile (I), the rate of this reaction was studied in
two states. The reaction rates in the frst state in ODW and
the second state in MDW were investigated. The reaction
rates were followed spectrophotometrically by monitoring
the changes in the absorption spectrum of the reaction mix-
ture in the UV–visible region as the same previous step.
Figures 10 and 11 show the absorption spectra of the reac-
tion mixture in ODW and MDW, respectively. The higher
absorbance changes at 308 nm indicate a faster reaction rate
or a faster rate of product formation pyrano[2,3‐d]pyrim-
idine (4a). Comparison of the spectra in Figs. 10 and 11
shows that the reaction rate in MDW is faster than that in
ODW. Since the rate of reaction between benzaldehyde (2a)
and malononitrile (3) in MDW is faster than that in ODW,
1 3

Journal of the Iranian Chemical Society
2.5
2
Micro-analysis was performed on a Perkin–Elmer 240-B
micro-analyzer. A Rayleigh UV-2601 spectrophotometer
was used to record the spectra for solutions of the reactants,
products, and reaction mixtures in 1.0 cm quartz cells over
the range of 220–380 nm at a 0.5 nm interval.
1min
7min
13min
19min
25min
31min
37min
43min
49min
1.5
1
Preparation of MDW
0.5
0
Deionized water (5 mL) was frst put in a test tube, which
was then put between two neodymium magnets NdFeB
(10 cm × 5 cm × 4 cm) with a magnetic feld of 0.8 T for
15 min. The test tube was subsequently removed from the
instrument and used for the reaction.
220
240
260
280
300
320
340
360
380
Wavelength(nm)
Fig. 11 The absorption spectra of the reaction mixture in MDW with
a scan time interval of 6 min against an aqueous solution of 50%
methanol (v/v) as the blank
General procedure for the synthesis of pyrno[2,3‑d]
pyrimidines (4a–n)
benzylidene malononitrile (I), as the reaction intermediate,
is formed more rapidly in MDW. When the reaction is car-
ried out in one pot, the rapid formation of the intermediate
in MDW causes its reaction with dimethyl barbituric acid
(1a) to be faster in MDW than that in ODW, and the product
pyrano[2,3‐d]pyrimidines (4a) is formed faster in MDW.
A round-bottomed fask (10 mL) was charged with dime-
thyl barbituric acid (1a) (1.0 mmol), malononitrile (3)
(1.0 mmol), and aldehyde (2) (1.0 mmol) added in MDW
(5 mL). Then the mixture was heated at 70 °C. After the
reaction was completed, the precipitate thus formed was fl-
tered and washed with 10 mL of water; the solid products
obtained were nearly pure. The desired products of high
purity were further achieved by recrystallization from etha-
nol to aford the desired products (Table 3).
Conclusion
We described a catalyst-free, environmentally-friendly,
and efcient synthesis of pyrano[2,3‐d]pyrimidines and
pyrido[2,3‐d]pyrimidines in MDW as a green-promoting
medium. Here, we used MDW as an inexpensive and ‘green’
solvent for the reaction medium. Cleaner reaction profle,
additive-free reagent, low costs, column-free workup con-
dition, shorter reaction times, high-to-excellent yields, and
eco-friendly make this present procedure an interesting
alternative to multistep approaches. Moreover, a UV–vis-
ible study shows the rate of reaction between substrates in
MDW is faster than that in ODW.
7‑Amino‑5‑(3‑bromophenyl)‑1,3‑dimethyl‑2,4‑di‑
oxo‑1,3,4,5‑tetrahydro‑2H‑pyrano‑[2,3‑d]‑pyrimi‑
dine‑6‑carbonitrile (4e)
1
White powder; MP 271–273 °C; H NMR (300 MHz,
DMSO-d6): 3.08 (s, 3H, CH3), 3.38 (s, 3H, CH3), 4.89
(s, 1H, CH), 7.13–7.18 (m, 1H, H-Ar), 7.31–7.38 (m, 3H,
H-Ar, NH2), 7.54–7.57 (d, 1H, H-Ar) ppm; Anal. Calcd.
for C16H13BrN4O3: C, 49.38; H, 3.37; N, 14.40. Found: C,
49.56; H, 3.46; N, 14.58.
7‑Amino‑5‑(3‑fuorophenyl)‑1,3‑dimethyl‑2,4‑di‑
oxo‑1,3,4,5‑tetrahydro‑2H‑pyrano‑[2,3‑d]‑pyrimi‑
dine‑6‑carbonitrile (4h)
Experimental
1
General
White powder; MP 227–229 °C; H NMR (300 MHz,
DMSO-d6): 3.10 (s, 3H, CH3), 3.36 (s, 3H, CH3), 4.39 (s,
1H, CH), 7.02–7.13 (m, 3H, H-Ar, NH2), 7.32–7.39 (m, 3H,
H-Ar) ppm; Anal. Calcd. for C16H13FN4O3: C, 58.54; H,
3.99; N, 17.07. Found: C, 58.72; H, 4.07; N, 17.22.
The reagents and solvents used were supplied from Merck,
Fluka, or Aldrich. Melting points were determined using
an electro-thermal C14500 apparatus. The reaction progress
and the purity of compounds were monitored using TLC
analytical silica gel plates (Merck 60 F250). The 1H NMR
(300 MHz) spectra were obtained using a Bruker Advance
DPX-250 FT-NMR spectrometer. The chemical shift values
were given as δ values against tetramethylsilane (TMS), as
the internal standard, and the J values were given in Hz.
1 3

Journal of the Iranian Chemical Society
7‑Amino‑5‑(4‑fourophenyl)‑1,3‑dimethyl‑2,4‑di‑
oxo‑1,3,4,5‑tetrahydro‑2H‑pyrano‑[2,3‑d]‑pyrimi‑
dine‑6‑carbonitrile (4i)
General procedure for the synthesis of pyrido[2,3‑d]
pyrimidines (6a–k)
To a 10-mL round-bottomed fask equipped with a heater
and containing MDW (5 mL) were added dimethyl barbi-
turic acid/barbituric acid (1) (1.0 mmol), malononitrile (3)
(1.0 mmol), aldehyde (2) (1.0 mmol), and ammonium ace-
tate (2.0 mmol). The reaction mixture was heated at 90 °C.
After completion of the reaction (by thin-layer chromatog-
raphy TLC), the precipitate was separated with fltration and
recrystallized from ethyl acetate to aford the pure products
(Table 4).
1
White powder; MP 225–227 °C; H NMR (300 MHz,
DMSO-d6): 3.10(s, 3H, CH3), 3.37 (s, 3H, CH3), 4.37 (s,
1H, CH), 7.09–7.15 (m, 3H, H-Ar, NH2), 7.28–7.37 (m, 2H,
H-Ar) ppm; Anal. Calcd. for C16H13FN4O3: C, 58.54; H,
3.99; N, 17.07. Found: C, 58.70; H, 4.06; N, 17.24.
7‑Amino‑5‑(2,4‑dichlorophenyl)‑1,3‑dime‑
thyl‑2,4‑dioxo‑1,3,4,5‑tetrahydro‑2H‑pyrano‑[2,3‑d]
‑pyrimidine‑6‑carbonitrile (4j)
7‑Amino‑5‑(2‑bromophenyl)‑1,3‑dimethyl‑2,4‑di‑
oxo‑1,2,3,4,5,8‑hexahydropyrido[2,3‑d]‑pyrimi‑
dine‑6‑carbonitrile (6b)
1
White powder; MP 251–253 °C; H NMR (300 MHz,
DMSO-d6): 3.08 (s, 3H, CH3), 3.38 (s, 3H, CH3), 4.87 (s,
1H, CH), 7.33–7.54 (m, 5H, H-Ar, NH2) ppm; Anal. Calcd.
for C16H12Cl2N4O3: C, 50.68; H, 3.19; N, 14.78. Found: C,
50.85; H, 3.11; N, 14.64.
1
White powder; MP 203–205 °C; H NMR (300 MHz,
DMSO-d6): 3.06 (s, 3H, CH3), 3.37 (s, 3H, CH3), 4.87 (s,
1H, CH), 7.10–7.17 (m, 1H, ArH), 7.30 (2H, ArH), 7.36 (s,
2H, NH, NH2), 7.54 (d, J=9 Hz, 1H, ArH) ppm.13C NMR
(75 MHz, DMSO-d6): 28.1, 29.6, 36.3, 57.8, 88.7, 118.9,
123.3, 128.6, 129.2, 130.8, 133.0, 143.3, 150.5, 152.0,
158.1, 160.8 ppm; Anal. Calcd. for C16H14BrN5O2: C, 49.50;
H, 3.63; N, 18.04. Found: C, 49.67; H, 3.70; N, 18.20.
7‑Amino‑5‑(4‑cyanophenyl)‑1,3‑dimethyl‑2,4‑di‑
oxo‑1,3,4,5‑tetrahydro‑2H‑pyrano‑[2,3‑d]‑pyrimi‑
dine‑6‑carbonitrile (4k)
1
White powder; MP 224–226 °C; H NMR (300 MHz,
DMSO-d6): 3.09(s, 3H, CH3), 3.37 (s, 3H, CH3), 4.47 (s,
1H, CH), 7.47–7.51 (m, 4H, H-Ar, NH2), 7.77–7.80 (m, 2H,
H-Ar) ppm; 13C NMR (75 MHz, DMSO-d6): 28.1, 29.6,
37.0, 57.9, 88.1, 58.1, 110.1, 119.2, 119.3, 129.03, 132.7,
150.4, 151.9, 158.1, 160.9 ppm; MS (EI), m/z [M]+ 335;
Anal. Calcd. for C17H13N5O3: C, 60.89; H, 3.91; N, 20.89.
Found: C, 60.71; H, 3.99; N, 20.75.
7‑Amino‑5‑(3‑bromophenyl)‑1,3‑dimethyl‑2,4‑di‑
oxo‑1,2,3,4,5,8‑hexahydropyrido[2,3‑d]‑pyrimi‑
dine‑6‑carbonitrile (6c)
1
White powder; MP 234–236 °C; H NMR (300 MHz,
DMSO-d6): 3.09 (s, 3H, CH3), 3.39 (s, 3H, CH3), 4.89 (s,
1H, CH), 7.21–7.41 (m, 6H, ArH, NH, NH2) ppm. 13C NMR
(75 MHz, DMSO-d6): 28.1, 29.6, 34.0, 57.8, 88.5, 119.0,
128.0, 128.9, 129.8, 130.7, 132.7, 141.6, 150.5, 152.0,
158.3, 160.8 ppm; MS (EI), m/z [M]+ 387; Anal. Calcd.
for C16H14BrN5O2: C, 49.50; H, 3.63; N, 18.04. Found: C,
49.65; H, 3.71; N, 18.22.
7‑Amino‑5‑(2‑nitrophenyl)‑1,3‑dimethyl‑2,4‑di‑
oxo‑1,3,4,5‑tetrahydro‑2H‑pyrano‑[2,3‑d]‑pyrimi‑
dine‑6‑carbonitrile (4l)
1
White powder; MP 241–243 °C; H NMR (300 MHz,
DMSO-d6): 3.04 (s, 6H, CH3), 5.14 (s, 1H, CH), 7.44–7.55
(m, 4H, H-Ar, NH2), 7.64–7.69 (t, 1H, H-Ar), 7.85–7.87 (d,
1H, H-Ar) ppm; MS (EI), m/z [M]+ 355; Anal. Calcd. for
C16H13N5O5: C, 54.09; H, 3.69; N, 19.71. Found: C, 54.30;
H, 3.77; N, 19.85.
7‑Amino‑5‑(2,4‑dichlorophenyl)‑1,3‑dime‑
thyl‑2,4‑dioxo‑1,2,3,4,5,8‑hexahydropyrido[2,3‑d]‑p
yrimidine‑6‑carbonitrile (6d)
1
White powder; MP 260–262 °C; H NMR (300 MHz,
7‑Amino‑5‑(4‑nitrophenyl)‑1,3‑dimethyl‑2,4‑di‑
oxo‑1,3,4,5‑tetrahydro‑2H‑pyrano‑[2,3‑d]‑pyrimi‑
dine‑6‑carbonitrile (4n)
DMSO-d6): 3.08 (s, 3H, CH3), 3.37 (s, 3H, CH3), 4.87 (s,
1H, CH), 7.35 (dd, J=9, 1.8 Hz 1H, ArH), 7.39 (1H, ArH),
7.43 (s, 2H, NH, NH2), 7.56 (d, J=1.8 Hz, 1H, ArH) ppm.
13C NMR (75 MHz, DMSO-d6): 28.1, 29.6, 33.7, 57.2,
88.1, 119.0, 128.2, 129.0, 132.2, 132.5, 133.7, 140.9, 150.5,
152.1, 158.3, 160.8 ppm; MS (EI), m/z [M]+ 377; Anal.
Calcd. for C16H13Cl2N5O2: C, 50.81; H, 3.46; N, 18.52.
Found: C, 50.99; H, 3.39; N, 18.67.
1
White powder; MP 212–214 °C; H NMR (300 MHz,
DMSO-d6): 3.09(s, 3H, CH3), 3.30 (s, 3H, CH3), 4.54 (s,
1H, CH), 7.50–7.59 (m, 4H, H-Ar, NH2), 8.16–8.19 (m, 2H,
H-Ar) ppm; Anal. Calcd. for C16H13N5O5: C, 54.09; H, 3.69;
N, 19.71. Found: C, 54.27; H, 3.61; N, 19.56.
1 3

Journal of the Iranian Chemical Society
7‑Amino‑5‑(2,6‑dichlorophenyl)‑1,3‑dime‑
thyl‑2,4‑dioxo‑1,2,3,4,5,8‑hexahydropyrido[2,3‑d]‑p
yrimidine‑6‑carbonitrile (6e)
7‑Amino‑5‑(2,4‑dichlorophenyl‑2,4‑di‑
oxo‑1,2,3,4,5,8‑hexahydropyrido[2,3‑d]pyrimi‑
dine‑6‑carbonitrile (6j)
1
White powder; MP 271–273 °C; H NMR (300 MHz,
White powder; MP>300 °C; 1H NMR (300 MHz, DMSO-
d6): 4.75 (s, 1H, CH), 7.22 (s, 2H, NH, NH2), 7.36 (s, 2H,
ArH), 7.54 (s, 1H, ArH), 11.01 (s, 1H, NH), 12.14 (s, 1H,
NH) ppm. 13C NMR (75 MHz, DMSO-d6): 33.3, 57.2, 87.6,
119.1, 128.1, 129.2, 132.3, 132.4, 133.7, 140.5, 150.0,
153.3, 158.4, 162.8 ppm; Anal. Calcd. for C14H9Cl2N5O2: C,
48.02; H, 2.59; N, 20.00. Found: C, 48.20; H, 2.68; N, 20.16.
DMSO-d6): 3.09 (s, 3H, CH3), 3.39 (s, 3H, CH3), 5.42 (s,
1H, CH), 7.29 (t, J=7.8 Hz, 1H, ArH,), 7.37 (d, J=9 Hz,
1H, ArH), 7.48–7.53 (m, 3H, ArH, NH, NH2) ppm. 13C
NMR (75 MHz, DMSO-d6): 28.1, 29.6, 33.4, 54.4, 86.9,
118.7, 129.0, 129.8, 130.8, 134.7, 136.1, 136.4, 150.3,
152.1, 159.1, 160.6 ppm; MS (EI), m/z [M]+ 377; Anal.
Calcd. for C16H13Cl2N5O2: C, 50.81; H, 3.46; N, 18.52.
Found: C, 50.65; H, 3.38; N, 18.37.
7‑Amino‑5‑(2,6‑dichlorophenyl‑2,4‑di‑
oxo‑1,2,3,4,5,8‑hexahydropyrido[2,3‑d]pyrimi‑
dine‑6‑carbonitrile (6k)
7‑Amino‑5‑(3‑fuorophenyl)‑1,3‑dimethyl‑2,4‑di‑
oxo‑1,2,3,4,5,8‑hexahydropyrido[2,3‑d]‑pyrimi‑
dine‑6‑carbonitrile (6f)
1
White powder; MP 262–264 °C; H NMR (300 MHz,
DMSO-d6): 5.32 (s, 1H, CH), 7.27–7.31 (m, 3H, ArH, NH,
NH2), 7.38 (d, J=7.5 Hz, 1H, ArH), 7.48 (d, J=7.8 Hz, 1H,
ArH), 11.08 (s, 1H, NH), 12.13 (s, 1H, NH) ppm. 13C NMR
(75 MHz, DMSO-d6): 32.6, 54.6, 86.5, 118.9, 129.0, 129.7,
130.8, 134.6, 136.2, 136.3, 150.0, 153.5, 159.2, 162.6 ppm;
MS (EI), m/z [M]+ 349; Anal. Calcd. for C14H9Cl2N5O2: C,
48.02; H, 2.59; N, 20.00. Found: C, 48.18; H, 2.50; N, 19.85.
1
White powder; MP 205–207 °C; H NMR (300 MHz,
DMSO-d6): 3.09 (s, 3H, CH3), 3.39 (s, 3H, CH3), 4.89 (s,
1H, CH), 7.21–7.41 (m, 6H, ArH, NH, NH2) ppm. 13C NMR
(75 MHz, DMSO-d6): 28.1, 29.6, 34.0, 57.7, 88.5, 119.0,
128.0, 128.9, 129.8, 130.7, 132.7, 141.6, 150.5, 152.0,
158.3, 160.8 ppm; Anal. Calcd. for C16H14FN5O2: C, 58.71;
H, 4.31; N, 21.40. Found: C, 58.89; H, 4.40; N, 21.55.
General procedure for the synthesis of pyrido[2,3‑d]
pyrimidines (6l–q)
7‑Amino‑5‑(2‑nitrophenyl)‑1,3‑dimethyl‑2,4‑di‑
oxo‑1,2,3,4,5,8‑hexahydropyrido[2,3‑d]‑pyrimi‑
dine‑6‑carbonitrile (6g)
To a 10-mL round-bottomed fask equipped with a heater
and containing MDW (5 mL) were added 4-aminouracile
(7) (1.0 mmol), aldehyde (2) (1.0 mmol), and malononitrile
(3) (1.0 mmol). The reaction mixture was heated at 80 °C.
After completion of the reaction (by thin-layer chromatogra-
phy TLC), the precipitated was separated with fltration and
recrystallized from ethyl acetate to aford the pure products
(Table 5).
1
White powder; MP 256–258 °C; H NMR (300 MHz,
DMSO-d6): 3.04 (s, 3H, CH3), 3.37 (s, 3H, CH3), 5.15 (s,
1H, CH), 7.47 (td, J = 9, 1.4 Hz 1H, ArH), 7.53–7.56 (m,
3H, ArH, NH, NH2), 7.67 (td, J = 7.5, 1.4 Hz, 1H, ArH),
7.86 (dd, J = 8.1 Hz, 1H, ArH) ppm. 13C NMR (75 MHz,
DMSO-d6): 28.1, 29.6, 36.3, 57.8, 88.7, 118.9, 123.3, 128.6,
129.2, 130.8, 133.0, 143.3, 150.5, 152.0, 158.1, 160.8 ppm;
MS (EI), m/z [M]+ 354; Anal. Calcd. for C16H14N6O4: C,
54.24; H, 3.98; N, 23.72. Found: C, 54.42; H, 4.06; N, 23.57.
Solutions
The malononitrile (3) solution (0.040 mol/L) was prepared
by dissolving malononitrile (3) (0.1345 g) in deionized water
in a 50-mL volumetric fask and diluting the solution to the
mark with deionized water. The benzaldehyde (2a) solution
(0.040 mol/L) was prepared by dissolving benzaldehyde (2a)
(0.20 mL) in methanol (5.0 mL) in a 50-mL volumetric fask
and diluting the solution to the mark with deionized water.
The solution of benzylidene malononitrile (I) (0.045 mol/L)
was prepared by dissolving benzylidene malononitrile (I)
(0.0691 g) in 10 mL methanol and diluting the solution to
the mark with deionized water. A solution of dimethyl bar-
bituric acid (1a) (0.0018 mol/L) was prepared by dissolv-
ing dimethyl barbituric acid (1a) (0.0790 g) in 10.0 mL of
methanol in a 250-mL volumetric fask, and the solution
7‑Amino‑5‑(4‑nitrophenyl)‑1,3‑dimethyl‑2,4‑di‑
oxo‑1,2,3,4,5,8‑hexahydropyrido[2,3‑d]‑pyrimi‑
dine‑6‑carbonitrile (6i)
1
White powder; MP 228–230 °C; H NMR (300 MHz,
DMSO-d6): 3.09 (s, 3H, CH3), 3.38 (s, 3H, CH3), 4.55 (s,
1H, CH), 7.50 (s, 2H, NH, NH2), 7.58 (d, J = 9 Hz, 2H,
ArH), 8.18 (d, J=9 Hz, 2H, ArH) ppm. 13C NMR (75 MHz,
DMSO-d6): 28.1, 29.7, 36.9, 57.8, 88.2, 119.2, 124.0, 124.9,
129.3, 131.9, 146.9, 150.5, 151.9, 152.2, 158.2, 161.0 ppm;
MS (EI), m/z [M]+ 354; Anal. Calcd. for C16H14N6O4: C,
54.24; H, 3.98; N, 23.72. Found: C, 54.02; H, 3.90; N, 23.86.
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Journal of the Iranian Chemical Society
was diluted with deionized water to the mark. A solution
of pyrno[2,3-d]pyrimidines (4a) was prepared by dissolv-
ing pyrno[2,3-d]pyrimidines (4a) (0.0111 g) in 10.0 mL of
DMSO in a 250-mL volumetric fask, and the solution was
diluted with deionized water to the mark. All the diluted
solutions were prepared in deionized water.
(0.0018 mol/L) were initially magnetized for 15 min in an
applied magnetic feld simultaneously. Then the same proce-
dure was applied to follow the reaction rate in MDW.
Acknowledgments We gratefully acknowledge the fnancial support
of the Research Council of the Shahrood University of Technology.
General procedure for monitoring reaction rate
between benzaldehyde (2a) and malononitrile (3)
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Afliations
Mohammad Bakherad1 · Ghadamali Bagherian1 · Amin Rezaeifard1 · Fatemeh Mosayebi1 · Behzad Shokoohi1 ·
Ali Keivanloo1
1
* Mohammad Bakherad
Faculty of Chemistry, Shahrood University of Technology,
Shahrood 3619995161, Iran
m.bakherad@yahoo.com
* Ghadamali Bagherian
Gh_bagherian@shahroodut.ac.ir
1 3