Fast and efficient synthesis of chromeno[d]pyrimidinediones catalysed by a TiO2-SiO2 nanocomposite in aqueous media

Article abstract of DOI:10.3184/174751917X14949407124706

A 1:1 TiO₂-SiO₂ nanocomposite was used as an efficient and green recyclable catalyst for the synthesis in water of 11 chromeno[d] pyrimidinediones, six of which are new. All reactions were carried out under very mild conditions to af

Full text of DOI:10.3184/174751917X14949407124706

JOURNAL OF CHEMICAL RESEARCH 2017
VOL. 41 JUNE, 337–340
RESEARCH PAPER 337
Fast and efficient synthesis of chromeno[d]pyrimidinediones catalysed by a
TiO2–SiO2 nanocomposite in aqueous media
Mehrdad Kiania, Shahrzad Abdolmohammadia,b* and Simin Janitabar-Darzic
aDepartment of Chemistry, East Tehran Branch, Islamic Azad University, PO Box 18735-138, Tehran, Iran
bYoung Researchers and Elite Club, East Tehran Branch, Islamic Azad University, PO Box 18735-138, Tehran, Iran
cNuclear Fuel Cycle Research School, Nuclear Science and Technology Research Institute AEOI, Tehran, Iran
A 1:1 TiO2–SiO2 nanocomposite was used as an efficient and green recyclable catalyst for the synthesis in water of 11 chromeno[d]
pyrimidinediones, six of which are new. All reactions were carried out under very mild conditions to afford the corresponding products in
excellent yields.
Keywords: aqueous media, chromeno[d]pyrimidinediones, recyclability of catalyst, TiO2–SiO2 nanocomposite
Chromene derivatives fused with N-containing heterocycles
display a broad spectrum of bioactivities and have seen use as
antioxidant,1,2 anticancer,3–6 antimicrobial,7–10 and hypotensive
agents,11 and as a local anesthetic.12 In addition, they can be
used as cognitive enhancement drugs13,14 for the treatment of
neurodegenerative diseases, including Alzheimer’s disease15
and schizophrenia disorder.16
Currently, nanostructured metal oxides, which possess good
physical and chemical abilities, promote numerous organic
transformations. Titanium dioxide nanoparticles (TiO2 NPs)
are considered very close to ideal nanocatalysts due to their high
efficiency and because they are non-toxic, inexpensive, moisture
stable and reusable.17 In view of these facts, we have already reported
the use of TiO2 NPs as an efficient heterogeneous catalyst in some
organic transformations, i.e., solvent-free synthesis of hexahydro-
2-quinolinecarboxylic acid derivatives18 and one-pot four-
component coupling reactions for the preparation of indeno[1,2-b]
quinolinediones,19 and tetrahydrobenzo[c]acridinones,20 in aqueous
media. In addition, we have noted that TiO2 NPs over silica shells
(TiO2–SiO2 nanocomposite) improves their catalytic efficiency
owing to an increase in surface area.21
3 in aqueous media by using a TiO2–SiO2 nanocomposite with a
molar ratio of 1:1 as an efficient and green catalyst (Scheme 1).
Two previous reports used Zr(HSO4)422 and melamine trisulfonic
acid23 as acid catalysts and the same starting materials to
prepare similar compounds in yields of 87–95% in solvent-free
processes at 100–110 °C. Our hope was to conduct the process
in water under less harsh conditions and exploit the impressive
catalytic abilities of nanoparticles to prepare some of the same
compounds in higher yield and some new ones. To the best of our
knowledge, there have been no reports so far of the synthesis of
these compounds using any nanocatalyst.
Results and discussion
In preliminary experiments, we prepared the TiO2–SiO2
nanocomposite catalyst according to a known non-thermal
sol-gel process.24 The crystalline structure and purity of
the synthesised nanocomposite was confirmed by X-ray
diffraction (XRD) analysis. The XRD results confirmed the
high crystallinity of the TiO2–SiO2 nanocomposite, which has
a crystalline anatase phase of TiO2 NPs in an amorphous silica
matrix (Fig. 1 in the ESI).
In view of the abovementioned biological activities of
substituted chromenes, we report herein a very simple route to
synthesise some 6,8-dimethyl-10-aryl-6,10-dihydro-7H-[1,3]
dioxolo[4′,5′:6,7]chromeno[2,3-d]pyrimidine-7,9(8H)-diones
(4a–k) via a condensation reaction of 1,3-dimethylbarbituric acid
1, an aromatic aldehyde (2a–k) and 3,4-methylenedioxyphenol
The transmission electron microscopy (TEM) image of the
TiO2–SiO2 nanocomposite (Fig. 2 in the ESI) also showed the
typical grainy structure of nanoparticles with sizes of 5–9
nm. The chemical composition of the nanocomposite was
determined by X-ray fluorescence (XRF) spectroscopy and
the results showed that the molar ratio was 1:1.
O
H
4'
5'
6'
3'
2'
1'
O
O
11
4
1
O
9
2
10
9d
8
N
7
10e
4e
11c
3c
O
N
Nano TiO2-SiO2
heat , solvent
2
+
O
3
O
5d
O
N
O
O
N
O
HO
6
5
1
3
4
2a, 4a Ar = C6H5, 2b, 4b Ar = 4-Br-C6H4, 2c, 4c Ar = 4-Cl-C6H4, 2d, 4d Ar = 2,4-Cl2-C6H3, 2e, 4e
Ar = 3-HO-C6H4, 2f, 4f Ar = 4-HO-C6H4, 2g, 4g Ar = 2-CH3-C6H4, 2h, 4h Ar = 4-CH3-C6H4, 2i, 4i
Ar = 3-O2N-C6H4, 2j, 4j Ar = Pyridine-4-yl, 2k, 4k Ar = Thiophen-2-yl
Scheme 1 Synthesis of chromeno[d]pyrimidinedione derivatives using a TiO2–SiO2 nanocomposite.
* Correspondent. E-mail: s.abdolmohamadi@yahoo.com; s.abdolmohamadi@iauet.ac.ir

338 JOURNAL OF CHEMICAL RESEARCH 2017
Table 1 Synthesis of a pentacyclic compound (4c; Ar = 4-Cl-C6H4) from
the reaction of 1,3-dimethylbarbituric acid 1, 4-chlorobenzaldehyde (2c;
Ar = 4-Cl-C6H4) and 3,4-methylenedioxyphenol 3 in the presence of a
TiO2–SiO2 nanocomposite (1:1) under different conditions (Scheme 1)a
Table 2 Yields of pentacyclic compounds (4; Ar = various) formed by
heating a mixture of 1,3-dimethylbarbituric acid 1, an araldehyde (2; Ar
= various), 3,4-methylenedioxyphenol 3 and a TiO2–SiO2 nanocomposite
in water at 80 °C for various times (Scheme 1)a
M.p. (°C)
Nanocatalyst
Temp.
(°C)
Time
(min)
Yield
(%)b
Yield Time
(%)b (min)
Entry
Solvent
Product Ar
(mol% with respect to TiO2)
Observed
Literature
lit.22 245–246
1
2
3
4
5
6
7
8
no catalyst
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
80
80
80
80
80
80
70
90
80
80
80
90
60
45
45
60
80
50
45
45
45
45
trace
80
96
96
79
74
78
95
77
74
4a
4b
4c
4d
4e
4f
C6H5
4-Br-C6H4
4-Cl-C6H4
95
98
96
94
96
97
94
95
96
97
96
45
40
45
55
50
45
50
45
40
45
40
242–244
268–270
255–257
277–279
265–267
272–274
236–238
248–250
260–262
279–281
276–278
TiO2–SiO2 (10%)
TiO2–SiO2 (15%)
TiO2–SiO2 (20%)
nano TiO2 (20%)
nano SiO2 (20%)
TiO2–SiO2 (15%)
TiO2–SiO2 (15%)
TiO2–SiO2 (15%)
TiO2–SiO2 (15%)
TiO2–SiO2 (15%)
–
lit.22 254–255
2,4-Cl2-C6H3
3-HO-C6H4
4-HO-C6H4
2-CH3-C6H4
4-CH3-C6H4
3-O2N-C6H4
pyridine-4-yl
thiophen-2-yl
lit.22 277–278
–
–
–
4g
4h
4i
4j
4k
lit.22 248–249
lit.22 262–263
9
10
11
EtOH
CH3CN
CH2Cl2
–
–
65
aReaction conditions: a stirred mixture of 1,3-dimethylbarbituric acid 1 (1 mmol),
3,4-methylenedioxyphenol 3 (1 mmol), an araldehyde (2; Ar = various) (1 mmol) and a
TiO2–SiO2 nanocomposite (1:1, 15 mol%) in water (5 mL) was heated at 80 °C for various
times.
bYields refer to those of pure isolated products characterised by IR, 1H NMR and 13C NMR
spectral data and by elemental analyses.
aReaction conditions: a stirred mixture of 1,3-dimethylbarbituric acid 1 (1 mmol),
3,4-methylenedioxyphenol 3 (1 mmol), 4-chlorobenzaldehyde (2c; Ar = 4-Cl-C6H4) (1
mmol) and a TiO2–SiO2 nanocomposite (1:1) in solvent (5 mL) was heated at various
temperatures and for various times.
bIsolated yield.
O
N
N
Ar
O
O
TiO2 NPs
H
O
H
SiO2
Ti
O
O
5
O
O
N
O
N
Ar
SiO2
O
H
N
N
N
OH
+
Ar
H
O
O
O
N
O
OH
O
2
1
6
O
N
Ar
N
H
H2O
O
O
O
O
HO
Ti
O
O
3
SiO2
7
O
Ar
O
N
H
O
O
N
O
H
O
O
Ti
O
SiO2
Ar
O
N
8
O
O
N
O
O
H
O
Ti
O
O
SiO2
9
TiO2 NPs
SiO2
O
N
Ar
O
N
Ar
O
H
O
O
O
O
N
O
O
N
O
H2O
OH
10
4
Scheme 2 Suggested mechanism for the reaction of 1,3-dimethylbarbituric acid 1, aromatic aldehydes 2 and 3,4-methylenedioxyphenol 3 catalysed
by a TiO2–SiO2 nanocomposite.

JOURNAL OF CHEMICAL RESEARCH 2017 339
nanocomposite powder was filtered and washed with distilled water
and then air dried at ambient temperature.24 The synthesised catalyst
was fully characterised by XRD, TEM and XRF techniques.
Using TiO2–SiO2 as a catalyst, we chose the model reaction
of 1,3-dimethylbarbituric acid 1, 4-chlorobenzaldehyde (2c; Ar
= 4-Cl-C6H4) and 3,4-methylenedioxyphenol 3 (Scheme 1) in
water to optimise the reaction conditions. The results are shown
in Table 1. Using 10 mol% TiO2–SiO2 at 80 °C, the expected
product (4c; Ar = 4-Cl-C6H4) was formed in 80% yield in 60
min (entry 2). In the absence of a catalyst, only a trace of product
was obtained even after 90 min (entry 1). We investigated the
optimum catalyst loading and the results indicated that 15 mol%
of catalyst was sufficient (entries 2–4). The catalytic efficiency
of two commercial nanopowders, TiO2 NPs (10–30 nm, anatase
TiO2) and SiO2 NPs (20 nm, non-porous) was tested, but 20
mol% of each produced the desired product 4c in only 79 and
74% yields, respectively (entries 5 and 6). To find the optimum
reaction temperature, the model reaction was carried out at
different temperatures. The results showed that the yield was
not affected by the temperature increasing above 80 °C (entries
7 and 8). Then, we tested other solvents. We found that the best
yield of product is obtained in aqueous media (entries 3 and
9–11).
Synthesis of chromeno[d]pyrimidinediones (4a–k); general procedure
A mixture of 1,3-dimethylbarbituric acid 1 (156 mg, 1 mmol), an
aromatic aldehyde 2a–k (1 mmol), 3,4-methylenedioxyphenol 3 (138
mg, 1 mmol) and the TiO2–SiO2 nanocomposite (21 mg, 15 mol%)
in H2O (5 mL) was stirred at 80 °C for 40–55 min. After reaction
completion, as indicated by TLC, the reaction mixture was filtered and
the residue was treated with hot ethanol (5 mL) and then centrifuged
at 2000–3000 rpm for 10 min to recover the catalyst. The recovered
catalyst was then washed with ethanol for reuse and air dried at
ambient temperature for several hours. The pure product was obtained
by cooling the ethanol solution to room temperature, dilution with H2O
(1 mL) and crystallisation.
6,8-Dimethyl-10-phenyl-6,10-dihydro-7H-[1,3]dioxolo[4′,5′:6,7]
chromeno[2,3-d]pyrimidine-7,9(8H)-dione (4a): White powder;
m.p. 242–244 °C (lit.34 245–246 °C); yield 346 mg (95%); IR (KBr)
(νmax cm−1): 3077, 2967, 2874, 1708, 1686, 1653, 1590, 1487, 1434,
1
1378, 1295; H NMR: δ 3.26 (s, 3H, N6CH3), 3.57 (s, 3H, N8CH3),
(s, 1H, H10), 5.89
5.94 (d, J = 1.3 Hz,
(d, J = 1.3 Hz, 1H, H2),
5.02
1H,
We then applied the optimised procedure to determine yields
when various substituted aromatic aldehydes were in reaction
with 1,3-dimethylbarbituric acid and 3,4-methylenedioxyphenol
(Table 2). The isolated compounds (4a–k) were characterised
),
H2′ 6.52 (s, 1H, C11H), 6.66 (s, 1H, C4H), 7.21 (m, 5H, ArH);
13C NMR: δ 28.0, 29.2, 40.1, 90.1, 97.7, 101.6, 109.7, 116.8, 127.9, 129.2,
129.3, 140.2, 145.0, 146.7, 146.9, 150.8, 152.4, 161.8. Anal. calcd for
65.93
4.43
66.04
; N, 7.69; found: C, ; H,
C20H16N2O5 (364.36): C,
4.59
; H,
1
by IR, H NMR and 13C NMR spectroscopic data and also by
; N, 7.57%.
6,8-Dimethyl-10- (4-bromophenyl) -6,10-dihydro-7H-[1,3]
dioxolo[4′,5′:6,7]chromeno[2,3-d]pyrimidine-7,9(8H)-dione (4b):
elemental analyses.
A suggested mechanism for the formation of product 4 is given
in Scheme 2. It is feasible that the TiO2 NPs participate in two
catalytic steps. In the initial step, the formation of alkene 7 is the
result of a Knoevenagel condensation between metal-activated
aromatic aldehyde 2 and enolised 1,3-dimethylbarbituric acid
1, via intermediates 5 and 6. 3,4-Methylenedioxyphenol 3 then
adds to metal-activated alkene 7 to generate the Michael adduct
9 via intermediate 8. Further cyclisation of 9 gives product 4,
after dehydration.
Also, we evaluated the recycling of the TiO2–SiO2
nanocomposite catalyst using the model reaction, which yielded
4c. However, there was no significant loss of activity after four
runs (product yields: 96, 95, 93 and 91%).
White powder; m.p. 268–270 °C; yield 434 mg (98%); IR (KBr) (νmax
cm−1): 3041, 2965, 2887, 1710, 1670, 1656, 1601, 1488, 1431, 1381,
1301 1H NMR: δ 3.28 (s, 3H, N6CH3), 3.55 (s, 3H, N8CH3), 5.01
;
(s, 1H, H10), 5.91
5.95 (d, J = 0.9 Hz, 1H,
(d, J = 0.9 Hz, 1H, H2),
),
J = 8.0 Hz,
2H,
H2′ 6.50 (s, 1H, C11H), 6.65 (s, 1H, C4H), 7.37 (d,
J = 8.0 Hz,
C2′H, C6′H), 7.47 (d,
2H, C3′H, C5′H); 13C NMR: δ 28.2,
29.6, 38.2, 89.7, 98.1, 101.5, 109.7, 117.7, 122.5, 124.2, 136.4, 140.2,
146.5, 146.8, 147.3, 150.3, 152.4, 162.6. Anal. calcd for C20H15BrN2O5
54.20
3.41
; N, 6.32; found: C,
54.03
3.53
; H, ; N,
(443.25): C,
6.46%.
; H,
6,8-Dimethyl-10- (4-chlorophenyl) -6,10-dihydro-7H-[1,3]
dioxolo[4′,5′:6,7]chromeno[2,3-d]pyrimidine-7,9(8H)-dione
(4c):
White powder; m.p. 255–257 °C (lit.34 254–255 °C); yield 383 mg
(96%); IR (KBr) (νmax cm−1): 3085, 2958, 2862, 1707, 1675, 1660,
Experimental
1576, 1478, 1430, 1352, 1298 1H NMR: δ 3.27 (s, 3H, N6CH3), 3.54
;
All of the chemical materials used in this work were purchased from
Merck and Sigma-Aldrich and used without further purification.
Melting points were determined on an Electrothermal 9100 apparatus
and are uncorrected. IR spectra were obtained on an ABB FTIR
(s, 1H, H10), 5.92
5.97
(s, 3H, N8CH3), 5.01
(d, J = 1.0 Hz, 1H, H2),
(d, J = 1.0 Hz, 1H,
),
H2′ 6.47 (s, 1H, C11H), 6.67 (s, 1H, C4H), 7.19
J = 7.0 Hz,
J = 7.0 Hz,
2H, C3′H, C5′H);
(d,
2H, C2′H, C6′H), 7.22 (d,
13C NMR: δ 28.1, 29.0, 39.6, 89.6, 98.1, 101.9, 108.0, 116.1, 128.1, 128.8,
1
(FTLA 2000) spectrometer. H NMR and 13C NMR spectra were
132.7, 143.0, 143.6, 145.7, 147.4, 150.6, 152.8, 161.7. Anal. calcd for
recorded on a Bruker DRX-500 Avance at 500 and 125 MHz,
respectively, using TMS as an internal standard and DMSO-d6
as the solvent. Elemental analyses were carried out using a Foss-
Heraeus CHN-O-rapid analyser. The TEM image of the catalyst was
obtained on a Philips EM208 transmission electron microscope under
acceleration. Powder XRD data were determined on a Philips, X’Pert
diffractometer using Cu Kα radiation (λ = 1.54 Å). The composition
analysis of catalyst was carried out by XRF spectroscopy using Oxford
ED 2000 equipment.
60.24
3.79 60.07
; N, 7.02; found: C, ; H,
C20H15ClN2O5 (398.80): C,
3.66
; H,
, N, 6.83%.
6,8-Dimethyl-10-(2,4-dichlorophenyl)-6,10-dihydro-7H-[1,3]
dioxolo[4′,5′:6,7]chromeno[2,3-d]pyrimidine-7,9(8H)-dione (4d):
White powder; m.p. 277–279 °C (lit.34 277–278 °C); yield 407 mg
(94%); IR (KBr) (νmax cm−1): 3080, 2969, 2875, 1700, 1668, 1647,
1568, 1477, 1433, 1388, 1291 1H NMR: δ 3.27 (s, 3H, N6CH3), 3.57
;
(s, 1H, H10), 5.92
5.96
(d, J = 1.2 Hz, 1H, H2),
(s, 3H, N8CH3), 5.12
(d, J = 1.2 Hz, 1H,
),
H2′ 6.55 (s, 1H, C11H), 6.63 (s, 1H, C4H), 7.12
(m, 2H, C5′H, C6′H), 7.36 (m, 1H, C3′H); 13C NMR: δ 28.1, 29.0, 38.6,
88.2, 98.0, 101.9, 107.5, 115.1, 127.6, 129.7, 131.2, 133.2, 133.5, 141.0,
142.7, 145.6, 147.5, 150.7, 153.1, 161.7. Anal. calcd for C20H14Cl2N2O5
Preparation of TiO2–SiO2 nanocomposite catalyst
Titanium tetrachloride (2 mL) was added dropwise to deionised water
(200 mL) in an ice-water bath with strong magnetic stirring. After
the hydrolysis was completed, the released HCl was neutralised with
dilute NH4OH to pH 7. The solid produced was filtered off and washed
with distilled water and then dispersed into a 0.3 M HNO3 aqueous
solution (200 mL) to remove all the chloride ions. The mixture was
then refluxed under strong stirring at 70 °C for 16 h to yield a titania
sol. Tetraethylorthosilicate (25 mL) was added dropwise into the
above sol and stirred at 70 °C for about 0.5 h. Finally, the TiO2–SiO2
55.45
3.26
55.63
3.12
; N, 6.31%.
(433.25): C,
6,8-Dimethyl-10-(3-hydroxyphenyl)-6,10-dihydro-7H-[1,3]
dioxolo[4′,5′:6,7]chromeno[2,3-d]pyrimidine-7,9(8H)-dione (4e):
; H,
; N, 6.47; found: C,
; H,
Yellow powder; m.p. 265–267 °C; yield 363 mg (96%); IR (KBr) (νmax
cm−1): 3181, 3064, 2925, 2851, 1709, 1688, 1651, 1600, 1532, 1362,
1
;
(s,
),
H2′
1292 H NMR: δ 3.27 (s, 3H, N6CH3), 3.53 (s, 3H, N8CH3), 4.99
1H, H10), 5.92
5.97 (d, J = 1.2 Hz, 1H,
(d, J = 1.2 Hz, 1H, H2),

340 JOURNAL OF CHEMICAL RESEARCH 2017
6.49 (s, 1H, C11H), 6.67 (s, 1H, C4H), 7.14 (m, 1H, C4′H), 7.40 (m,
3H, C2′H, C5′H, C6′H), 9.41 (s, 1H, OH); 13C NMR: δ 28.7, 30.0, 39.6,
90.2, 97.7, 101.5, 109.0, 114.6, 116.4, 116.9, 119.3, 120.1, 140.2, 145.5,
146.9, 147.5, 150.8, 152.3, 158.1, 163.2. Anal. calcd for C20H16N2O6
6,8-Dimethyl-10- (thiophen-2-yl) -6,10-dihydro-7H-[1,3]
dioxolo[4′,5′:6,7]chromeno[2,3-d]pyrimidine-7,9(8H)-dione (4k):
White powder; m.p. 276–278 °C; yield 359 mg (96%); IR (KBr)
(νmax cm−1): 3074, 2969, 2851, 1709, 1682, 1655, 1571, 1484, 1429,
1366, 1275 1H NMR: δ 3.26 (s, 3H, N6CH3), 3.55 (s, 3H, N8CH3),
63.16
4.24
63.04
4.33
; H, ; N,
;
(380.35): C,
7.57%.
; H,
; N, 7.36; found: C,
(s, 1H, H10), 5.87
5.94 (d, J = 0.9 Hz,
(d, J = 0.9 Hz, 1H, H2),
4.98
1H,
6,8-Dimethyl-10-(4-hydroxyphenyl)-6,10-dihydro-7H-[1,3]
dioxolo[4′,5′:6,7]chromeno[2,3-d]pyrimidine-7,9(8H)-dione (4f):
),
H2′ 6.45 (s, 1H, C11H), 6.64 (s, 1H, C4H), 7.05 (m, 3H, ArH);
13C NMR: δ 28.2, 29.1, 39.4, 88.9, 98.0, 101.7, 109.4, 115.4, 122.6, 127.5,
White powder; m.p. 272–274 °C; yield 369 mg (97%); IR (KBr) (νmax
138.9, 145.8, 146.5, 147.4, 150.1, 151.8, 152.6, 162.1. Anal. calcd for
cm−1): 3188, 3085, 2931, 2866, 1711, 1689, 1636, 1570, 1475, 1430,
58.37
; H,
3.81 58.42
; N, 7.56; found: C, ; H,
C18H14N2O5S (370.38): C,
3.92
1386, 1297 1H NMR: δ 3.25 (s, 3H, N6CH3), 3.54 (s, 3H, N8CH3),
;
; N, 7.48%.
(s, 1H, H10), 5.88
5.95 (d, J = 1.0 Hz,
4.97
(d, J = 1.0 Hz, 1H, H2),
Acknowledgement
1H,
),
J = 8.4 Hz,
2H, C3′H, C5′H), 9.38 (s, 1H,
H2′ 6.50 (s, 1H, C11H), 6.66 (s, 1H, C4H), 7.54 (d,
J = 8.4 Hz,
2H, C2′H, C6′H), 7.88 (d,
We thank the Research Council of East Tehran Branch, Islamic
Azad University for financial support of this research.
OH); 13C NMR: δ 28.8, 29.4, 38.9, 90.0, 98.4, 101.4, 109.0, 114.5, 116.3,
124.6, 139.2, 146.5, 147.0, 148.0, 151.8, 153.1, 157.3, 163.5. Anal. calcd
63.16
4.24
63.28
; N, 7.36; found: C, ; H
for C20H16N2O6 (380.35): C,
4.34
; H,
Electronic Supplementary Information
,
; N, 7.29%.
6,8-Dimethyl-10- (2-methylphenyl)-6,10-dihydro-7H-[1,3]
dioxolo[4′,5′:6,7]chromeno[2,3-d]pyrimidine-7,9(8H)-dione (4g):
The ESI is available through:
stl.publisher.ingentaconnect.com/content/stl/jcr/supp-data
White powder; m.p. 236–238 °C; yield 356 mg (94%); IR (KBr) (νmax
Received 24 February 2017; accepted 8 May 2017
Paper 1704619
https://doi.org/10.3184/174751917X14949407124706
Published online: 23 May 2017
cm−1): 3049, 2955, 2871, 1712, 1672, 1639, 1594, 1490, 1428, 1375,
1
;
C2’CH
1260 H NMR: δ 2.29 (s, 3H,
3), 3.28 (N6CH3), 3.57 (s, 3H,
5.96 (d,
(s, 1H, H10), 5.90
N8CH3), 5.01
(d, J = 1.0 Hz, 1H, H2),
J = 1.0 Hz, 1H,
3H, C3′H, C4′H, C5′H), 7.23 (m, 1H, C6′H); C NMR: δ
),
H2′ 6.47 (s, 1H, C11H), 6.68 (s, 1H, C4H), 7.15 (m,
13
20.8,
27.9,
References
28.7, 39.5, 89.8, 98.5, 102.4, 108.9, 115.7, 126.2, 127.6, 130.1, 131.0,
135.6, 141.2, 146.1, 146.8, 148.5, 151.3, 152.9, 162.8. Anal. calcd for
1
2
3
L. Alvey, S. Prado, V. Huteau, B. Saint-Joanis, S. Michel, M. Koch, S.T.
Cole, F. Tillequin and Y.L. Janin, Bioorg. Med. Chem., 2008, 16, 8264.
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7124.
66.66
4.79 66.51
; N, 7.40; found: C, ; H,
C21H18N2O5 (378.38): C,
4.50
; H,
; N, 7.64%.
6,8-Dimethyl-10- (4-methylphenyl)-6,10-dihydro-7H-[1,3]
dioxolo[4′,5′:6,7]chromeno[2,3-d]pyrimidine-7,9(8H)-dione
(4h):
White powder; m.p. 248–250 °C (lit.34 248–249 °C); yield 359 mg
(95%); IR (KBr) (νmax cm−1): 3075, 2956, 2870, 1705, 1672, 1642,
4
5
6
F. Cheng, A. Ishikawa, Y. Ono, T. Arrheniusa and A. Nadzana, Bioorg.
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Blais, G. Attardo, R. Denis, S. Lamothe, H. Gourdeau, B. Tseng, J. Drewe
and X. Cai, Bioorg. Med. Chem. Lett., 2008, 18, 5571.
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Farmaco, 2002, 57, 715.
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Lett., 2005, 15, 4295.
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1
;
C4′CH
3), 3.28
1603, 1476, 1434, 1396, 1273 H NMR: δ 2.25 (s, 3H,
(s, 1H, H10), 5.90
(s, 3H, N6CH3), 3.54 (s, 3H, N8CH3), 4.99
(d, J = 0.9
5.95 (d, J = 0.9 Hz, 1H,
),
H2′ 6.52 (s, 1H, C11H), 6.67 (s,
Hz, 1H, H2),
J = 8.0 Hz,
J = 8.0 Hz,
1H, C4H), 7.07 (d,
2H, C3′H, C5′H), 7.15 (d,
20.9
2H, C2′H, C6′H); 13C NMR: δ
, 28.1, 29.0, 38.9, 90.1, 98.0, 101.8,
7
8
9
108.3, 116.6, 127.7, 129.3, 136.5, 142.3, 143.0, 145.5, 147.1, 150.7, 152.5,
66.66 4.79
161.9. Anal. calcd for C21H18N2O5 (378.38): C,
66.75 4.81
; H,
; N, 7.40;
found: C,
; H,
; N, 7.33%.
6,8-Dimethyl-10- (3-nitrophenyl) -6,10-dihydro-7 H-[1,3]
dioxolo[4′,5′:6,7]chromeno[2,3-d]pyrimidine-7,9(8H)-dione
(4i): Pale yellow powder; m.p. 260–262 °C (lit.34 262–263 °C); yield
393 mg (96%); IR (KBr) (νmax cm−1): 3056, 2943, 2850, 1702, 1666,
10 R.R. Kumar, S. Perumal, P. Senthilkumar, P. Yogeeswari and D. Sriram,
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12 M. Longobardi, A. Bargagna, E. Mariani, P. Schenone, S. Vitagliano, L.
Stella, A. Di Sarno and E. Marmo, Farmaco, 1990, 45, 399.
13 A.H. Bedair, N.A. El-Hady, A. El-Latif, A.H. Fakery and A.M. El-Agrody,
Farmaco, 2000, 55, 708.
14 M.M-Heravi, K. Bakhtiari, V. Zadsirjan, F. Bamoharram and O. M-Heravi,
Bioorg. Med. Chem. Lett., 2007, 17, 4262.
15 C. Brühlmann, F. Ooms, P.A. Carrupt, B. Testa, M. Catto, F. Leonetti, C.
Altomare and A. Carotti, J. Med. Chem., 2001, 44, 3195.
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Wise, J. Med. Chem., 1999, 42, 3718.
17 S.M. Sajadi, M. Naderi and S. Babadoust, J. Nat. Sci. Res., 2011, 1, 10.
18 S. Abdolmohammadi, Chin. Chem. Lett., 2012, 23, 1003.
19 S. Abdolmohammadi, Chin. Chem. Lett., 2013, 24, 318.
20 S. Abdolmohammadi, M. Mohammadnejad and F. Shafaei, Z. Naturforsch.,
2013, 68b, 362.
21 M. Haghighi and K. Nikoofar, J. Saudi Chem. Soc., 2016, 20, 101.
22 J. Zhang, W.L. Li and L.Q. Wu, J. Braz. Chem. Soc., 2011, 22, 1236.
23 W. Li and Q. Luo, E-. J. Chem., 2011, 8, 1972.
24 A. Nilchi, S. Janitabar-Darzi and S. Rasouli-Garmarodi, Mater. Sci. Appl.,
2011, 2, 476.
1659, 1529, 1486, 1351, 1224 1H NMR: δ 3.27 (s, 3H, N6CH3), 3.57
;
(s, 1H, H10), 5.94
5.98
(d, J = 1.0 Hz, 1H, H2),
(s, 3H, N8CH3), 5.15
(d, J = 1.0 Hz, 1H,
),
H2′ 6.44 (s, 1H, C11H), 6.77 (s, 1H, C4H), 7.47
(m, 3H, C4′H, C5′H, C6′H), 7.96 (m, 1H, C2′H); 13C NMR: δ 28.1,
29.0, 39.1, 88.8, 98.4, 102.1, 107.9, 115.0, 122.8, 128.4, 129.3, 134.5,
143.0, 145.9, 147.1, 147.8, 148.5, 150.5, 152.8, 161.8. Anal. calcd for
58.68
3.69 58.61
; N, 10.27; found: C, ; H,
C20H15N3O7 (409.35): C,
3.54
; H,
; N, 10.14%.
6,8-Dimethyl-10- (pyridin- 4-yl) - 6,10-dihydro-7 H- [1,3]
dioxolo[4′,5′:6,7]chromeno[2,3-d]pyrimidine-7,9(8H)-dione (4j):
Pale yellow powder; m.p. 279–281 °C; yield 343 mg (97%); IR (KBr)
(νmax cm−1): 3066, 2974, 2846, 1704, 1670, 1661, 1587, 1478, 1432,
1364, 1287 1H NMR: δ 3.27 (s, 3H, N6CH3), 3.56 (s, 3H, N8CH3),
;
(s, 1H, H10), 5.93
5.97 (d, J = 1.1 Hz, 1H,
(d, J = 1.1 Hz, 1H, H2),
5.11
),
H2′ 6.50 (s, 1H, C11H), 6.67 (s, 1H, C4H), 7.36 (d, J = 8.1 Hz, 2H,
C2′H, C6′H), 8.43 (d, J = 8.1 Hz, 2H, C3′H, C5′H); 13C NMR: δ 28.1,
29.3, 40.1, 90.6, 99.2, 102.8, 108.5, 116.1, 126.7, 146.6, 147.7, 148.3,
150.1, 150.9, 151.2, 153.1, 163.7. Anal. calcd for C19H15N3O5 (365.34):
62.46
4.14
62.56 4.01
; H, ; N, 11.42%.
C,
; H,
; N, 11.5; found: C,