Synthesis and in vitro evaluation of antioxidant activity of diverse naphthopyranopyrimidines, diazaanthra[2,3-d][1,3]dioxole-7,9-dione and tetrahydrobenzo[a]xanthen-11-ones

Article abstract of DOI:10.1039/c2ra22406b

A green and efficient one pot three component protocol has been developed for the synthesis of naphthopyranopyrimidines, diazaanthra[2,3-d][1,3]dioxole-7, 9-dione and tetrahydrobenzo[a]xanthen-11-ones in PEG-400 catalyzed by alum (KAl(SO₄)

Full text of DOI:10.1039/c2ra22406b

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Synthesis and in vitro evaluation of antioxidant activity
of diverse naphthopyranopyrimidines, diazaanthra[2,3-
d][1,3]dioxole-7,9-dione and
Cite this: DOI: 10.1039/c2ra22406b
tetrahydrobenzo[a]xanthen-11-ones3
Jitender M. Khurana,* Anshika Lumb, Ankita Chaudhary and Bhaskara Nand
A green and efficient one pot three component protocol has been developed for the synthesis of
naphthopyranopyrimidines, diazaanthra[2,3-d][1,3]dioxole-7,9-dione and tetrahydrobenzo[a]xanthen-11-
ones in PEG-400 catalyzed by alum (KAl(SO4)2?12H2O). Single crystal X-ray diffraction studies have been
performed for naphthopyranopyrimidine (5). The synthesized compounds were screened for in vitro
antioxidant activity by DPPH scavenging assay and compounds 3 and 4 manifested profound antioxidant
potential.
Received 5th October 2012,
Accepted 19th November 2012
DOI: 10.1039/c2ra22406b
www.rsc.org/advances
Recently, alum (KAl(SO4)2?12H2O) which is inexpensive, water-
soluble and nontoxic has emerged as economic and excellent
Introduction
catalyst for the synthesis of organic compounds.15 Polyethylene
glycol (PEG) has been reported as an interesting solvent system,
which is non-toxic, inexpensive and non-ionic liquid solvent of
low volatility, for a variety of reactions.16 Therefore, we decided to
investigate a green and efficient protocol for the synthesis of
series of novel naphthopyranopyrimidines, diazaanthra[2,3-
d][1,3]dioxole-7,9-dione and tetrahydrobenzo[a]xanthen-11-ones
in PEG-400 catalyzed by KAl(SO4)2?2H2O.
Development of novel synthetic methodologies to facilitate the
preparation of libraries of compounds is important for
modern
medicinal
and
combinatorial
chemistry.1
Multicomponent reactions (MCRs) have become an important
tool for the creation of molecular complexity and diversity.2 N-
and O-Heterocycles hold a position of prominence due to their
applications as biologicals, pharmacophores, pharmaceuticals
and agrochemicals. Pyranopyrimidines show wide range of
useful physiological,3 antimicrobial,4 analgesic, and antic-
onvulsant activities.5 Moreover, naphthopyranopyrimidines
and its derivatives are important structural motifs in medic-
inal and pharmaceutical chemistry6 as they show antibacterial
and antifungal activities.7,8 Furthermore, xanthenes have also
attracted a great deal of interest due to their wide gamut of
biological properties like antiviral,9 antibacterial,10 and anti-
inflammatory11 activities as well as sensitizers in photody-
namic therapy12 and antagonists for the paralyzing action of
zoxazolamine.13 Recently, several multicomponent strategies
have been reported for the synthesis of napthopyranopyrimi-
dines and tetrahydrobenzo[a]xanthen-11-ones utilizing differ-
ent types of catalysts.14 The reported methods show varying
degrees of successes as well as limitations. Therefore, there
still remains a high demand for the development of more
general, efficient, economically viable, and eco-compatible
protocol to assemble such scaffolds.
The generation of free radicals during metabolic processes
is responsible for human conditions such as aging, cancer,
atherosclerosis, arthritis, viral infection stroke, myocardial
infraction etc. Antioxidants act as a major defense against
radical mediated toxicity by inhibiting the free radicals. In
recent years, compounds which exhibit DPPH (2,2-diphenyl-1-
picrylhydrazyl) radical scavenging activity are receiving atten-
tion.17 It can be inferred from the literature that phenolic
compounds usually possess potential antioxidant activity
because of phenolic hydroxy groups which act as a hydrogen
or electron donors18 but little attention has been paid to
explore the antioxidant activity of substituted naphthopyrano-
pyrimidines and xanthene derivatives. Therefore, the synthe-
sized compounds were evaluated for in vitro antioxidant
activity by DPPH radical scavenging assay method.
Results and discussion
Department of Chemistry, University of Delhi, Delhi-110007, India.
E-mail: jmkhurana1@yahoo.co.in; Fax: 91 11 27666605; Tel: 91 11 27667725
Chemistry
Electronic supplementary information (ESI) available. CCDC 877858. For
3
In the present study, we have reported KAl(SO4)2?2H2O
catalyzed PEG-400 mediated synthesis of diversely substituted
crystallographic data in CIF or other electronic format see DOI: 10.1039/
C2RA22406B
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napthopyranopyrimidines (3a–o, 4a–b and 5a–d) and diazaan-
thra[2,3-d] [1,3]dioxole-7,9-dione (6a–f) by one pot condensa-
tion of aldehydes and N,N-dimethylbarbituric acid with 2,7-
dihydroxynaphthalene (1a) or 2,6-dihydroxynaphthalene (1b)
or 2-hydroxynaphthalene (1c) or benzo[1,3]dioxol-5-ol (1d)
respectively. The protocol has been also applied for the
synthesis of tetrahydrobenzo[a]xanthen-11-ones (7a–e and
8a–e) by condensation of 2,7-dihydroxynaphthalene, aldehydes
and cyclic-1,3-dicarbonyl compounds, namely 5-methyl-cyclo-
hexane-1,3-dione (1e) and cyclohexane-1,3-dione (1f).
optimized conditions (Scheme 1). All the reactions proceeded
smoothly and resulted in the synthesis of 12-aryl-2-hydroxy-
8,12-dihydro-8,10-dimethyl-9H-naphtho[19,29 : 5,6]pyrano[2,3-
d]pyrimidine-9,11-(10H)-dione (3a–o, Table 1), 3-hydroxy-
12-aryl-2-8,12-dihydro-8,10-dimethyl-9H-naphtho[19,29 : 5,6]
pyrano[2,3-d]pyrimidine-9,11-(10H)-dione (4a–b, Table 2), 12-
aryl-8,12-dihydro-8,10-dimethyl-9H-naphtho
[19,29 : 5,6]pyr-
ano[2,3-d]pyrimidine-9,11-(10H)-dione (5a-d, Table 2) and 10-
(4-chlorophenyl)-6,8-dimethyl-6,10-dihydro-5-oxa-6,8-diazaanthra
[2,3-d][1,3]dioxole-7,9-dione (6a–f, Table 2). This protocol tolerates
a variety of aromatic aldehydes containing electron-withdrawing
and electron-donating substituents.
Initially, the three component cyclocondensation of 4-chlor-
obenzaldehyde (1.0 mmol), 2,7-dihydroxynaphthalene 1a (1.0
mmol) and N,N-dimethylbarbituric acid (1.2 mmol) was
examined in PEG-400 without any catalyst. After 3 h of heating
at 60 uC, two new products were observed on TLC but the
reaction remained incomplete even after 24 h of heating. The
newly formed products were separated by column chromato-
graphy and were identified to be 12-(4-chlorophenyl)-2-hydroxy-
8,12-dihydro-8,10-dimethyl-9H-naphtho[19,29 : 5,6]pyrano[2,3-d]
pyrimidine-9,11-(10H)-dione (3a) and 5-(4-chlorobenzylidene)-
1,3-dimethylpyrimidine-2,4,6-trione (2) by spectral analysis.
However, the desired product naphthopyranopyrimidine (3a)
was formed only in 20% while the Knoevenagel condensation
product (2) was formed as the major one in 58% yield (Table 1,
entry 1). The above reaction was then attempted in presence of
Lewis acids i.e. NaBr, TMSCl, LiCl, La(OTf)3, CeCl3?7H2O and
KAl(SO4)2?12H2O in PEG-400 at 60 uC (Table 1). We observed that
reaction using 15 mol% of KAl(SO4)2?12H2O proceeded effi-
ciently and gave 92% of the desired product 3a. In view of its
ease to handle and cost effectiveness we decided to pursue the
reactions with KAl(SO4)2?12H2O (alum). The reaction using 10
mol% of alum gave inferior yield while reaction with 20 mol% of
alum was not affected (entries 6 and 7, Table 1). The reactions
attempted in PEG-200 and PEG-600 in an analogous manner
resulted in the formation of the desired product 3a in 71% and
82% respectively (entries 10–11, Table 1).
Additionally, the structure of the synthesized derivative (5a)
has been confirmed by single crystal X-ray diffraction analysis
(Fig. 1), see ESI.
3
We further extended this synthetic protocol for one pot,
three component condensation of aldehydes (1.0 mmol), 2,7-
dihydroxy naphthalene 1a (1.0 mmol) and cyclic-1,3-dicarbonyl
compounds (5,5-dimethylcyclohexane-1,3-dione (1e) and cyclo-
hexane-1,3-dione (1f)) (1.2 mmol) using KAl(SO4)2?12H2O in
PEG-400 at 60 uC. The reactions yielded 2-hydroxy-9,9-
dimethyl-12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthen-11-ones
(Table 1, 7a–e) and 12-aryl-2-hydroxy-8,9,10,12-tetrahydroben-
zo[a]xanthen-11-ones (Table 1, 8a–e) in good yields (Scheme 2).
The plausible mechanism for the formation of naphthopyr-
anopyrimidines is proposed in Scheme 3. The reaction
proceeded via ortho-quinone methide intermediate, which
was formed by the nucleophilic addition of b-naphthol to
aldehydes catalyzed by KAl(SO4)2?12H2O. Michael addition
between
ortho-quinone
methide
(1)
and
N,N-dimethylbarbituric acid and subsequent intramolecular
cyclization and elimination of H2O afforded the desired
product 5. The proposed mechanism was supported by the
fact that when the reaction of 5-(4-chlorobenzylidene)-1,3-
dimethylpyrimidine-2,4,6-trione (2) and 2-naphthol was car-
ried out under similar reaction conditions, no reaction was
observed (Scheme 4) which supports our proposed mechan-
ism.
The condensation of N,N-dimethylbarbituric acid, aromatic
aldehydes and 2,7-dihydroxynaphthalene (1a)/2,6-dihydroxy
naphthalene (1b)/2-hydroxynaphthalene (1c) or benzo[1,3]-
dioxol-5-ol (1d) was then carried out under the above
The recyclability of PEG-400 was also investigated during the
synthesis of 3a. After completion, the reaction was quenched
Table 1 Effect of catalyst on the condensation of 4-chlorobenzaldehyde, 2,7-
dihydroxynaphthalene and N,N-dimethylbarbituric acid (molar ratio 1 : 1 : 1.2)
Loading
(mol%)
Yield
3a (%)
Entry
Solvent
Catalyst
Time
1
2
3
4
5
6
7
8
9
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-200
PEG-600
None
NaBr
TMSCl
LiCl
—
15
15
15
15
15
15
10
20
15
15
24 h
7 h
7 h
6 h
7 h
45 min
45 min
70 min
45 min
4 h
20a,b
50b
—
c
40b
53b
85
92
60
91
71
82
La(OTf)3
CeCl3?7H2O
KAl(SO4)2?12H2O
KAl(SO4)2?12H2O
KAl(SO4)2?12H2O
KAl(SO4)2?12H2O
KAl(SO4)2?12H2O
10
11
3 h
a
b
Incomplete reaction. Yields after column chromatography.
Mixture of products.
Scheme 1 Synthesis of naphthopyranopyrimidines and diazaanthra[2,3-
d][1,3]dioxole-7,9-diones.
c
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Table 2 Synthesis of naphthopyranopyrimidines, diazaanthra[2,3-d][1,3]diox-
ole-7,9-diones and tetrahydrobenzo[a]xanthen-11-ones
Entry
Ar
Product
Yield (%)
Time (min)
1
2
3
4
5
6
7
8
9
4-ClC6H4
2-ClC6H4
3-ClC6H4
2,4-Cl2C6H3
4-OMeC6H4
2-OMeC6H4
3,4,5-(OMe)3C6H2
4-MeC6H4
4-O2NC6H4
3-O2NC6H4
2-O2NC6H4
4-CNC6H4
4-F3CC6H4
C6H5
3a
3b
3c
3d
3e
3f
3g
3h
3i
92
87
84
86
82
82
76
82
89
83
89
78
85
85
87
83
89
84
86
84
78
75
72
80
72
75
75
86
84
82
87
85
83
86
89
88
84
45
40
40
60
70
90
90
70
40
45
60
50
60
90
35
45
35
50
50
60
45
90
60
50
60
90
75
45
60
50
50
75
60
40
75
45
60
Scheme 2 Synthesis of tetrahydrobenzo[a]xanthen-11-ones.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
3j
3k
3l
3m
3n
3o
4a
4b
5a
5b
5c
5d
6a
6b
6c
6d
6e
6f
7a
7b
7c
7d
7e
8a
8b
8c
8d
8e
4-FC6H4
4-ClC6H4
4-O2NC6H4
4-ClC6H4
4-O2NC6H4
4-FC6H4
4-F3CC6H4
4-ClC6H4
3-ClC6H4
4-MeC6H4
4-FC6H4
4-O2NC6H4
C6H5
4-ClC6H4
4-CF3C6H4
4-FC6H4
4-O2NC6H4
4-OMeC6H4
4-ClC6H4
4-O2NC6H4
C6H5
4-F3CC6H4
4-MeC6H4
Scheme 3 Mechanism for the synthesis of napthopyranopyrimidines.
consistent results for three runs. The results are summarized
in Fig. 2.
Radical scavenging assay
The electronic absorption spectra of solutions of 3a–o, 4a–b,
5a–d, 6a–f, 7a–e and 8a–e (2 6 1024 M) were measured in
DMSO. All the compounds showed two absorption maxima
(lmax) located between 310 and 350 nm. All these compounds
were screened for their antioxidant activity by measuring their
scavenging ability towards 2,2-diphenyl-1-picrylhydrazyl
(DPPH) radical. The disappearance of DPPH was measured
spectrophotometrically at 517 nm using butylated hydroxy
toluene (BHT) as standard. All the results are summarized in
Fig. 3.
It can be inferred from Fig. 3 that the majority of
compounds 3 and 4 showed higher radical scavenging activity
compared to BHT whereas compounds 5, 6, 7 and 8 showed
lower scavenging activity except 5b. The higher scavenging
activity in 3 could be attributed to the formation of two
radicals I and II (Scheme 5) both of which are stabilized by
resonance. Similarly compounds 4 also give two resonance
stabilized radicals and show comparable activity to com-
pounds 3. The OH position does not seem to have any
significant effect. The difference in the activity of 3a–o could
be due to the difference in the stability of the radicals I and II.
Compounds bearing electron-withdrawing groups, 3a, 3d, 3i,
3j, 3k, 3l and 3o, showed a higher hydrogen donor ability
with water and the solid product was collected by filtration.
The filtrate containing polyethylene glycol was rinsed with
ether and further vacuumed to dryness at 90 uC for 2 h to
remove any trapped water, to afford PEG-400 which was reused
directly for the next run. The reaction proceeded with nearly
Scheme 4 Reaction of 5-(4-chlorobenzylidene)-1,3-dimethyl-pyrimidine-2,4,6-
Fig. 1 Ortep diagram of compound 5a drawn with 50% probability ellipsoid.
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Scheme 5
JNM ECX-400P at 400 MHz and Bruker Avance Spectrospin 300
MHz, using TMS as an internal standard. The chemical shift
values are recorded on the d scale and the coupling constants
(J) are in Hertz. Elemental analysis was performed by a Vario
EL III Elementar analyzer. X-Ray intensity data was collected
on an Oxford Diffraction Xcalibur CCD diffractometer with
graphite monochromated Mo-Ka radiation (l = 0.71073 Å) at
temperature 298 K.
Fig. 2 Recycling yields. Reactions of 2,7-dihydroxynaphthalene, 4-chloroben-
zaldehyde, N,N-dimethylbarbituric acid, KAl(SO4)2?12H2O and PEG-400.
towards DPPH radical compared to compounds 3e, 3h and 3g
having electron donating groups. On the other hand,
compounds 5 and 6 do not have any phenolic OH groups
and therefore can form only benzylic radicals (III) and (IV)
respectively that results in the lower activity. The lower activity
in xanthenes 7 and 8, though they contain a phenolic hydroxyl
group, could be attributed to the absence of the pyrimidine
moiety in which the lone pair on the nitrogen stabilizes the
free radical.
General procedure for the synthesis of
naphthopyranopyrimidines and diazaanthra[2,3-
d][1,3]dioxole-7,9-diones
A mixture of aldehyde (1.0 mmol), 1a/1b/1c/1d (1.0 mmol),
N,N-dimethylbarbituric acid (1.2 mmol), alum (15 mol%) and
5 mL of PEG-400 was placed in a 50 mL round-bottomed flask.
The mixture was stirred at 60 uC for the appropriate time as
mentioned in Table 1. After completion of the reaction as
monitored by TLC using ethyl acetate : petroleum ether
(30 : 70, v/v) as eluent, the mixture was allowed to cool at
room temperature and quenched with water (10–15 mL). The
precipitate thus formed was collected by filtration at pump,
washed with water and then with ethanol : water (1 : 1) to
afford pure diazabenzo[a]anthracene-9,11-diones.
Experimental
All the chemicals used were purchased from Sigma-Aldrich
and were used as received. Silica gel 60 F254 (Precoated
aluminium plates) from Merck was used to monitor reaction
progress. Melting points were determined on a Tropical
Labequip apparatus and are uncorrected. IR (KBr) spectra
were recorded on a Perkin-Elmer FTIR spectrophotometer and
the values are expressed as nmax cm21. Absorbance measure-
General procedure for the synthesis of tetrahydrobenzo
[a]xanthen-11-ones
In a 50 mL round bottomed flask, aldehyde (1.0 mmol), 2,7-
dihydroxynaphthalene (1.0 mmol), 1e or 1f (1.0 mmol), alum
(15 mol%) and 5 mL of PEG-400 were taken. The reaction
mixture was heated at 60 uC for the appropriate time as
mentioned in Table 1. The progress of the reaction was
monitored by TLC using ethyl acetate : petroleum ether
ments were made using
a Analytikjena Specord 250
Spectrophotometer. Mass spectral data were recorded on
JEOL-AccuTOF mass spectrometer having a DART source.
The 1H NMR and 13C NMR spectra were recorded on a Jeol
Fig. 3 (%) DPPH radical scavenging activity.
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(40 : 70, v/v) as eluent. After completion of the reaction, the
reaction mixture was allowed to cool to room temperature and
quenched with water (y10–15 mL). The precipitate formed
was collected by filtration at pump, washed with water and
then ethanol : water (1 : 1) to yield pure tetrahydrobenzo[a]x-
anthen-11-ones.
28.95, 27.68 ppm; IR (KBr) nmax, cm21 = 3225, 1660, 1620, 1458,
1220; MS (ESI) m/z Calcd. for C23H17ClN2O4: 420.09, Found:
421.16 [M+ + H], 423.10 [M+ + H + 2]; Anal. Calcd. for
C
23H17ClN2O4: C, 65.64; H, 4.07; N, 6.66; Found: C, 65.61; H,
4.04; N, 6.64; UV (2 6 1024 M solution in DMSO) lmax (e) : 314
nm (0.315 6 104 L mol21 cm21), 326 (0.441 6 104 L mol21
cm21).
DPPH free radical scavenging assay
12-(3-Chlorophenyl)-2-hydroxy-8,12-dihydro-8,10-dimethyl-
9H-naphtho[19,29 : 5,6]pyrano[2,3-d]pyrimidine-9,11-(10H)-
dione (3c, C23H17ClN2O4)
A methanol solution of 2,2-diphenyl-1-picrylhydrazyl (DPPH)
was used as a reagent for the spectrophotometric assay with
modifications.19 3 mM solutions of naphthopyranopyrimi-
dines, diazaanthra[2,3-d][1,3]dioxole-7,9-diones and tetrahy-
drobenzo[a]xanthen-11-ones were prepared using DMSO. 1 mL
of 0.1 mM methanolic solution of DPPH was added to a 3 mL
solution of the compound and the mixture was shaken
vigorously using a vortex mixer. Absorbance was read against
a blank at 517 nm after incubation of the reaction mixtures for
60 min in the dark at room temperature. Butylated hydroxyl
toluene (BHT) was used as a reference compound. The radical
scavenging activities were expressed as the inhibition percen-
tage and were calculated using the formula:
White solid; Yield = 84%; M.p.: .300 uC (decom.); Rf 0.40
(petroleum ether : EtOAc, 60 : 40 v/v); 1H NMR (400 MHz,
DMSO-d6): d = 9.99 (s, 1H, OH), 7.86 (d, J = 8.8 Hz, 1H, Ar), 7.79
(d, J = 8.8 Hz, 1H, Ar), 7.35 (d, J = 8.8 Hz, 2H, Ar), 7.24–7.14 (m,
4H, Ar), 7.01 (dd, 1,2J = 2.2, 1,3J = 8.8 Hz, 1H, Ar), 5.42 (s, 1H,
ArC_H_), 3.47 (s, 3H, NC_H_3), 3.14 (s, 3H, NC_H_3) ppm; 13C NMR
(100 MHz, DMSO-d6): d = 161.13, 156.75, 152.38, 150.05,
147.32, 146.35, 132.72, 131.94, 130.46, 130.11, 129.60, 127.99,
126.93, 126.63, 125.74, 117.68, 114.17, 113.33, 105.33, 89.41,
35.42, 28.95, 27.76 ppm; IR (KBr) nmax, cm21 = 3277, 1670,
1525, 1348, 1230; MS (ESI) m/z Calcd. for C23H17ClN2O4:
420.09, Found: 421.11 [M+ + H], 423.11 [M+ + H + 2]; Anal.
Calcd. for C23H17ClN2O4: C, 65.64; H, 4.07; N, 6.66; Found: C,
65.63; H, 4.05; N, 6.65; UV (2 6 1024 M solution in DMSO)
lmax (e) = 324 nm (0.260 6 104 L mol21 cm21), 337 (0.324 6
104 L mol21 cm21).
Radical scavenging activity (%) = [(A0 2 A1)/A0) 6 100]
where A0 is absorbance of the control (blank, without compound)
and A1 is the absorbance of the compound. All the tests were
carried out in triplicate and the results were averaged.
12-(4-Chlorophenyl)-2-hydroxy-8,12-dihydro-8,10-dimethyl-
9H-naphtho[19,29 : 5,6]pyrano[2,3-d]pyrimidine-9,11-(10H)-
dione (3a, C23H17ClN2O4)
12-(2,4-Dichlorophenyl)-2-hydroxy-8,12-dihydro-8,10-dimethyl-
9H-naphtho[19,29 : 5,6]pyrano[2,3-d]pyrimidine-9,11-(10H)-
dione (3d, C23H16Cl2N2O4)
White solid; Yield = 92%; M.p.: .300 uC (decom.); Rf 0.40
(petroleum ether : EtOAc, 60 : 40 v/v); 1H NMR (400 MHz,
DMSO-d6): d = 9.94 (s, 1H, OH), 7.83–7.75 (m, 2H, Ar), 7.31–
7.23 (m, 5H, Ar), 7.12 (s, 1H, Ar), 7.00 (dd, 1,2J = 2.2 Hz, 1,3J = 8.6
Hz, 1H, Ar), 5.39 (s, 1H, ArC_H_), 3.45 (s, 3H, NC_H_3), 3.13 (s, 3H,
NC_H_3) ppm; 13C NMR (100 MHz, DMSO-d6): d = 161.18,
156.75, 152.28, 150.12, 147.26, 143.10, 132.03, 131.16, 130.50,
130.13, 129.55, 128.20, 125.82, 117.70, 114.46, 113.39, 105.48,
89.68, 39.29, 28.99, 27.81 ppm; IR (KBr): nmax, cm21 = 3277,
1670, 1641, 1525, 1448, 1348, 1230; MS (ESI) m/z Calcd. for
C23H17ClN2O4: 420.09, Found: 421.16 [M+ + H], 423.15 [M+ + H
+ 2]; Anal. Calcd. for C23H17ClN2O4: C, 65.64; H, 4.07; N, 6.66;
Found: C, 65.62; H, 4.06, N, 6.62; UV (2 6 1024 M solution in
DMSO) lmax (e) = 325 nm (0.323 6 104 L mol21 cm21), 337
(0.411 6 104 L mol21 cm21).
White solid; Yield = 86%; M.p.: .300 uC (decom.); Rf 0.35
(petroleum ether : EtOAc, 60 : 40 v/v); 1H NMR (400 MHz,
DMSO-d6): d = 9.92 (s, 1H, OH), 7.80 (d, J = 8.8 Hz, 1H, Ar), 7.74
(d, J = 8.7 Hz, 1H, Ar), 7.44 (d, J = 2.2 Hz, 1H, Ar), 7.31–7.18 (m,
4H, Ar), 7.03 (dd, 1,2J = 2.2 Hz, 1,3J = 8.8 Hz, 1H, Ar), 5.64 (s, 1H,
ArC_H_), 3.49 (s, 3H, NC_H_3), 3.10 (s, 3H, NC_H_3) ppm; 13C NMR
(100 MHz, DMSO-d6): d = 160.92, 156.75, 152.40, 150.02,
147.26, 140.20, 133.42, 132.34, 131.90, 130.42, 129.78, 128.84,
127.40, 125.66, 117.54, 113.63, 113.28, 105.64, 88.57, 33.62,
28.95, 27.68 ppm; IR (KBr) nmax, cm21 = 3186, 1660, 1621, 1455,
1225; MS (ESI) m/z Calcd. for C23H16Cl2N2O4: 454.05, Found:
453.10 [M+ + H], 455.10 [M+ + H + 2]; Anal. Calcd. for
C23H16Cl2N2O4: C, 60.67; H, 3.54; N, 6.15; Found: C, 60.66; H,
3.56; N, 6.14; UV (2 6 1024 M solution in DMSO) lmax (e) = 325
nm (0.354 6 104 L mol21 cm21), 338 (0.440 6 104 L mol21
cm21).
12-(2-Chlorophenyl)-2-hydroxy-8,12-dihydro-8,10-dimethyl-
9H-naphtho[19,29 : 5,6]pyrano[2,3-d]pyrimidine-9,11-(10H)-
dione (3b, C23H17ClN2O4)
2-Hydroxy-12-(4-methoxyphenyl)-8,12-dihydro-8,10-dimethyl-
9H-naphtho[19,29 : 5,6]pyrano[2,3-d]pyrimidine-9,11-(10H)-
dione (3e, C24H20N2O5)
White solid; Yield = 87% ; M.p.: .300 uC (decom.); Rf 0.45
(petroleum ether : EtOAc, 60 : 40 v/v); 1H NMR (400 MHz,
DMSO-d6): d = 9.99 (s, 1H, OH), 7.86 (d, J = 8.8 Hz, 1H, Ar), 7.75
(d, J = 8.8 Hz, 1H, Ar), 7.33–7.26 (m, 4H, Ar), 7.18–7.09 (m, 2H,
Ar), 7.03 (dd, 1,2J = 2.2 Hz, 1,3J = 8.8 Hz, 1H, Ar), 5.70 (s, 1H,
ArC_H_), 3.48 (s, 3H, NC_H_3), 3.11 (s, 3H, NC_H_3) ppm; 13C NMR
(100 MHz, DMSO-d6): d 160.84, 156.66, 152.46, 150.06, 147.32,
141.05, 132.44, 132.31, 132.11, 130.34, 129.63, 129.57, 128.25,
127.22, 125.66, 117.49, 114.27, 113.31, 105.79, 89.05, 33.94,
White solid; Yield = 86%; M.p.: .300 uC (decom.); Rf 0.35
(petroleum ether : EtOAc, 60 : 40 v/v); 1H NMR (400 MHz,
DMSO-d6): d = 9.93 (s, 1H, OH), 7.82 (d, J = 8.6 Hz, 1H, Ar), 7.77
(d, J = 9.1 Hz, 1H, Ar), 7.32 (d, J = 9.16 Hz, 1H, Ar), 7.18–7.16
(m, 3H, Ar), 6.99 (dd, 1,2J = 1.8 Hz, 1,3J = 8.7 Hz, 1H, Ar), 6.75 (d,
J = 8.7 Hz, 2H, Ar), 5.36 (s, 1H, ArC_H_), 3.62 (s, 3H, OC_H_3), 3.46
(s, 3H, NC_H_3), 3.14 (s, 3H, NC_H_3) ppm; 13C NMR (100 MHz,
DMSO-d6): d = 160.98, 157.65, 151.38, 151.43, 148.29, 141.23,
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133.44, 132.35, 131.91, 130.44, 129.68, 128.81, 127.42, 125.69,
117.58, 113.61, 113.29, 105.66, 88.58, 55.69, 33.62, 28.95, 27.68
ppm; IR (KBr) nmax, cm21 = 3200, 1670, 1638, 1554, 1245; MS
(ESI) m/z Calcd. for C24H20N2O5: 416.14, Found: 453.1 [M+ + H],
455.1 [M+ + H + 2]; Anal. Calcd. for C24H20N2O5: C, 69.22; H,
4.84; N, 6.73; Found: C, 69.25; H, 4.81; N, 6.72; UV (2 6 1024 M
solution in DMSO) lmax (e) : 324 nm (0.273 6 104 L mol21
cm21), 337 (0.336 6 104 L mol21 cm21).
141.21, 135.47, 132.08, 130.35, 129.16, 128.75, 128.02, 125.75,
117.57, 115.22, 113.33, 105.55, 90.27, 35.17, 28.91, 27.73,
20.52; IR (KBr) nmax, cm21 = 3170, 1658, 1602, 1492, 1196; MS
(ESI) m/z Calcd. for C24H20N2O4: 400.14, Found: 401.20 [M+ +
H]; Anal. Calcd. for C24H20N2O4: C, 71.99; H, 5.03; N, 7.00;
Found: C, 71.96; H, 5.01; N, 6.98; UV (2 6 1024 M solution in
DMSO) lmax (e) : 323 nm (0.203 6 104 L mol21 cm21), 337
(0.250 6 104 L mol21 cm21).
2-Hydroxy-12-(2-methoxyphenyl)-8,12-dihydro-8,10-dimethyl-
9H-naphtho[19,29 : 5,6]pyrano[2,3-d]pyrimidine-9,11-(10H)-
dione (3f, C24H20N2O5)
2-Hydroxy-12-(4-nitrophenyl)-8,12-dihydro-8,10-dimethyl-
9H-naphtho[19,29 : 5,6]pyrano[2,3-d]pyrimidine-9,11-(10H)-
dione (3i, C23H17N3O6)
White solid; Yield = 82%; M.p.: .300 uC (decom.); Rf 0.30
(petroleum ether : EtOAc, 60 : 40 v/v); 1H NMR (400 MHz,
DMSO-d6): d = 9.82 (s, 1H, OH), 7.76–7.70 (m, 2H, Ar), 7.40 (s,
1H, Ar), 7.32–7.31 (m, 1H, Ar), 7.26 (d, J = 8.8 Hz, 1H, Ar), 7.09–
7.05 (m, 1H, Ar), 6.99–6.97 (m, 1H, Ar), 6.87–6.79 (m, 2H, Ar),
5.59 (s, 1H, ArC_H_), 3.71 (s, 3H, OC_H_3), 3.50 (s, 3H, NC_H_3),
3.14 (s, 3H, NC_H_3) ppm; 13C NMR (100 MHz, CDCl3): d =
160.81, 156.60, 152.46, 151.06, 147.32, 141.04, 132.44, 132.32,
132.11, 130.34, 129.63, 129.57, 128.25, 127.22, 125.66, 117.49,
114.27, 113.31, 105.79, 89.05, 55.98, 33.94, 28.95, 27.76 ppm;
IR (KBr) nmax, cm21 = 3160, 1660, 1630, 1550, 1240; MS (ESI) m/
z Calcd. for C24H20N2O5: 416.14, Found: 417.12 [M+ + H]; Anal.
Calcd. for C24H20N2O5: C, 69.22; H, 4.84; N, 6.73; Found: C,
69.24; H, 4.82; N, 6.71; UV (2 6 1024 M solution in DMSO)
lmax (e) = 325 nm (0.239 6 104 L mol21 cm21), 337 (0.298 6
104 L mol21 cm21).
Cream solid; Yield = 89%; M.p.: .300 uC (decom.); Rf 0.45
(petroleum ether : EtOAc, 50 : 50 v/v); 1H NMR (400 MHz,
DMSO-d6): d 9.99 (s, 1H, OH), 8.07 (d, J = 8.6 Hz, 2H, Ar), 7.86
(d, J = 8.7 Hz, 1H, Ar), 7.78 (d, J = 8.6 Hz, 1H, Ar), 7.56 (d, J = 8.7
Hz, 2H, Ar), 7.34 (d, J = 8.7 Hz, 1H, Ar), 7.10 (s, 1H, Ar), 6.99–
6.97 (m, 1H, Ar), 5.53 (s, 1H, ArC_H_), 3.46 (s, 3H, NC_H_3), 3.12
(s, 3H, NC_H_3) ppm; 13C NMR (100 MHz, DMSO-d6): d 161.11,
156.88, 152.45, 151.40, 150.08, 147.26, 146.14, 131.97, 130.53,
129.91, 129.56, 125.80, 123.49, 117.87, 113.65, 133.29, 105.50,
88.89, 35.79, 29.03, 27.90 ppm; IR (KBr) nmax, cm21 = 3241,
1660, 1554, 1245; MS (ESI) m/z Calcd. for C23H17N3O6: 431.11
Found: 432.11 [M+ + H]; Anal. Calcd. for C23H17N3O6 :C, 64.04;
H, 3.97; N, 9.74; Found: C, 64.06; H, 3.96; N, 9.72; UV (2 6
1024 M solution in DMSO) lmax (e) : 321 nm (0.223 6 104 L
mol21 cm21), 336 (0.608 6 104 L mol21 cm21).
2-Hydroxy-12-(3-nitrophenyl)-8,12-dihydro-8,10-dimethyl-
9H-naphtho[19,29 : 5,6]pyrano[2,3-d]pyrimidine-9,11-(10H)-
dione (3j, C23H17N3O6)
2-Hydroxy-12-(3,4,5-trimethoxyphenyl)-8,12-dihydro-8,10-
dimethyl-9H-naphtho[19,29 : 5,6]pyrano[2,3-d]pyrimidine-9,11-
(10H)-dione (3g, C26H24N2O7)
Cream solid; Yield = 83%; M.p.: .300 uC (decom.); Rf 0.35
(petroleum ether : EtOAc, 50 : 50 v/v); 1H NMR (400 MHz,
DMSO-d6): d = 9.97 (s, 1H, OH), 8.12 (s, 1H, Ar), 7.98 (d, J = 8.8
Hz, 1H, Ar), 7.88 (d, J = 8.7 Hz, 1H, Ar), 7.78 (d, J = 8.8 Hz, 1H,
Ar), 7.70 (d, J = 7.3 Hz, 1H, Ar), 7.51–7.48 (m, 1H, Ar), 7.37 (d, J
= 8.8 Hz, 1H, Ar), 7.09 (s, 1H, Ar), 6.98–6.96 (m, 1H, Ar), 5.55 (s,
1H, ArC_H_), 3.46 (s, 3H, NC_H_3), 3.12 (s, 3H, NC_H_3) ppm; 13C
NMR (100 MHz, DMSO-d6): d = 161.15, 156.86, 152.39, 150.05,
147.57, 147.38, 145.96, 134.96, 131.86, 130.52, 129.92, 125.77,
121.78, 117.77, 113.55, 113.29, 105.38, 88.97, 35.61, 28.97,
27.80 ppm; IR (KBr) nmax, cm21 = 3120, 1668, 1620, 1358, 1203;
MS (ESI) m/z Calcd. for C23H17N3O6: 431.11, Found: 432.18 [M+
+ H]; Anal. Calcd. for C23H17N3O6: C, 64.04; H, 3.97; N, 9.74;
Found: C, 64.06; H, 3.96; N, 9.72; UV (2 6 1024 M solution in
DMSO) lmax (e) = 323 nm (0.443 6 104 L mol21 cm21), 337
(0.457 6 104 L mol21 cm21).
White solid; Yield = 76%; M.p.: .300 uC (decom.); Rf 0.30
(petroleum ether : EtOAc, 60 : 40 v/v); 1H NMR (400 MHz,
DMSO-d6): d = 9.96 (s, 1H, OH), 7.84 (d, J = 8.8 Hz, 1H, Ar), 7.79
(d, J = 8.8 Hz, 1H, Ar), 7.34 (d, J = 8.8 Hz, 1H, Ar), 7.25 (s, 1H,
Ar), 7.01 (dd, 1,2J = 2.2 Hz, 1,3J = 8.6 Hz, 1H, Ar), 6.52–6.47 (m,
2H, Ar), 5.37 (s, 1H, ArC_H_), 3.63 (s, 6H, 2 6 OC_H_3), 3.53 (s,
3H, OC_H_3), 3.47 (s, 3H, NC_H_3), 3.16 (s, 3H, NC_H_3); 13C NMR
(100 MHz, DMSO-d6): d = 161.26, 156.61, 152.51, 152.42,
150.13, 147.35, 139.71, 136.13, 132.18, 130.41, 129.28, 125.74,
117.67, 115.01, 113.35, 105.59, 90.08, 59.82, 55.80, 35.78,
28.96, 27.82; IR (KBr) nmax, cm21 = 3190, 1640, 1615, 1412,
1220; MS (ESI) m/z Calcd. for C26H24N2O7: 476.48, Found:
477.23 [M+ + H]; Anal. Calcd. for C26H24N2O7 C, 65.54; H, 5.08;
N, 5.88; Found: C, 65.52; H, 5.06; N, 5.85; UV (2 6 1024
M
solution in DMSO) lmax (e) = 323 nm (0.307 6 104 L mol21
cm21), 337 (0.383 6 104 L mol21 cm21).
2-Hydroxy-12-(2-nitrophenyl)-8,12-dihydro-8,10-dimethyl-
9H-naphtho[19,29 : 5,6]pyrano[2,3-d]pyrimidine-9,11-(10H)-
dione (3k, C23H17N3O6)
2-Hydroxy-12-(4-methylphenyl)-8,12-dihydro-8,10-dimethyl-
9H-naphtho[19,29 : 5,6]pyrano[2,3-d]pyrimidine-9,11-(10H)-
dione (3h, C24H20N2O4)
Cream solid; Yield = 89%; M.p.: .300 uC (decom.); Rf 0.30
(petroleum ether : EtOAc, 50 : 50 v/v); 1H NMR (400 MHz,
DMSO-d6): d = 9.95 (s, 1H, OH), 8.11 (s, 1H, Ar), 7.97 (d, J = 8.8
Hz, 1H, Ar), 7.86 (d, J = 8.7 Hz, 1H, Ar), 7.76 (d, J = 8.8 Hz, 1H,
Ar), 7.70 (d, J = 7.3 Hz, 1H, Ar), 7.51–7.48 (m, 1H, Ar), 7.32 (d, J
= 8.8 Hz, 1H, Ar), 7.10 (s, 1H, Ar), 6.97–6.96 (m, 1H, Ar), 5.60 (s,
1H, ArC_H_), 3.47 (s, 3H, NC_H_3), 3.11 (s, 3H, NC_H_3) ppm; 13C
NMR (100 MHz, DMSO-d6): d = 161.14, 156.82, 152.38, 150.01,
White solid; Yield = 82%; M.p.: .300 uC (decom.); Rf 0.40
(petroleum ether : EtOAc, 60 : 40 v/v); 1H NMR (400 MHz,
DMSO-d6): d = 9.92 (s, 1H, OH), 7.82 (d, J = 9.5 Hz, 1H, Ar), 7.77
(d, J = 8.8 Hz, 1H, Ar), 7.33 (d, J = 8.8 Hz, 1H, Ar), 7.18–7.14 (m,
3H, Ar), 6.99 (d, J = 8.0 Hz, 3H, Ar), 5.36 (s, 1H, ArC_H_), 3.47 (s,
3H, NC_H_3), 3.13 (s, 3H, NC_H_3), 2.15 (s, 3H, CH3); 13C NMR
(100 MHz, DMSO-d6): d = 161.10, 156.56, 150.09, 147.22,
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147.56, 147.31, 145.96, 134.98, 131.81, 130.52, 129.92, 125.71,
121.76, 117.77, 113.55, 113.29, 105.38, 88.97, 35.61, 28.97,
27.80 ppm; IR (KBr) nmax, cm21 = 3124, 1660, 1621, 1350, 1230;
MS (ESI) m/z Calcd. for C23H17N3O6: 431.11, Found: 432.16 [M+
+ H]; Anal. Calcd. for C23H17N3O6 :C, 64.04; H, 3.97; N, 9.74;
Found: C, 64.03; H, 3.95; N, 9.71; UV (2 6 1024 M solution in
DMSO) lmax (e) = 323 nm (0.313 6 104 L mol21 cm21), 337
(0.436 6 104 L mol21 cm21).
147.31, 144.14, 132.09, 130.40, 129.27, 128.22, 128.18, 126.52,
125.78, 117.63, 115.11, 113.36, 105.50, 90.19, 35.59, 28.94,
27.77 ppm; IR (KBr) nmax, cm21 = 3145, 1672, 1668, 1548, 1256;
MS (ESI) m/z Calcd. for C23H18N2O4: 386.13, Found: 387.15 [M+
+ H]; Anal. Calcd. for C23H18N2O4: C, 71.49; H, 4.70; N, 7.25;
Found: C, 71.47; H, 4.73, N; 7.25; UV (2 6 1024 M solution in
DMSO) lmax (e) = 324 nm (0.293 6 104 L mol21 cm21), 337
(0.365 6 104 L mol21 cm21).
2-Hydroxy-12-(4-cyanophenyl)-8,12-dihydro-8,10-dimethyl-
9H-naphtho[19,29 : 5,6]pyrano[2,3-d]pyrimidine-9,11-(10H)-
dione (3l, C24H17N3O4)
2-Hydroxy-12-(4-fluorophenyl)-8,12-dihydro-8,10-dimethyl-
9H-naphtho[19,29 : 5,6]pyrano[2,3-d]pyrimidine-9,11-(10H)-
dione (3o, C23H17FN2O4)
Cream solid; Yield = 78%; M.p.: .300 uC (decom.); Rf 0.40
(petroleum ether : EtOAc, 60 : 40 v/v); 1H NMR (400 MHz,
DMSO-d6): d = 9.97 (s, 1H, OH), 7.87 (d, J = 8.8 Hz, 1H, Ar), 7.79
(d, J = 8.8 Hz, 1H, Ar), 7.69 (d, J = 8.0 Hz, 2H, Ar), 7.48 (d, J = 8.0
Hz, 2H, Ar), 7.35 (d, J = 8.8 Hz, 1H, Ar), 7.11–7.10 (m, 1H, Ar),
7.00 (dd, 1,2J = 2.2 Hz, 1,3J = 8.7 Hz, 1H, Ar), 5.49 (s, 1H, ArC_H_),
3.47 (s, 3H, NC_H_3), 3.13 (s, 3H, NC_H_3) ppm; 13C NMR (100
MHz, DMSO-d6): d = 161.06, 156.80, 152.45, 150.02, 149.33,
147.29, 132.18, 131.90, 130.48, 129.76, 129.29, 125.74, 118.64,
117.69, 113.74, 113.33, 109.40, 105.27, 89.00, 35.86, 28.96,
27.73 ppm; IR (KBr) nmax, cm21 = 3186, 1683, 1621, 1455, 1225;
MS (ESI) m/z Calcd. for C24H17N3O4: 411.12 Found: 412.18 [M+
+ H]; Anal. Calcd. for C24H17N3O4: C, 70.07; H, 4.16; N, 10.21;
Found: C, 70.05; H, 4.13; N, 10.18; UV (2 6 1024 M solution in
DMSO) lmax (e) = 325 nm (0.423 6 104 L mol21 cm21), 337
(0.504 6 104 L mol21 cm21).
White solid; Yield = 87%; M.p.: .300 uC (decom.); Rf 0.35
(petroleum ether : EtOAc, 60 : 40 v/v); 1H NMR (400 MHz,
DMSO-d6): d = 9.95 (s, 1H, OH), 7.84 (d, J = 8.8 Hz, 1H, Ar), 7.78
(d, J = 8.8 Hz, 1H, Ar), 7.33–7.26 (m, 3H, Ar), 7.15–7.14 (m, 1H,
Ar), 7.04–6.97 (m, 3H, Ar), 5.42 (s, 1H, ArC_H_), 3.47 (s, 3H,
NC_H_3), 3.14 (s, 3H, NC_H_3) ppm; 13C NMR (100 MHz, DMSO-
d6): d = 161.15, 156.68, 152.27, 150.09, 147.26, 140.25, 132.00,
130.44, 130.04, 129.96, 129.42, 125.78, 117.64, 115.04, 114.83,
113.35, 105.46, 89.94, 34.90, 28.94, 27.76 ppm; IR (KBr) nmax,
cm21 = 3170, 1658, 1620, 1445, 1198; MS (ESI). m/z Calcd. for
C23H17FN2O4: 404.09, Found: 405.17 [M+ + H]; Anal. Calcd. for
C
23H17FN2O4: C, 68.31; H, 4.24; N, 6.93; Found: C, 68.28; H,
4.26; N, 6.91; UV (2 6 1024 M solution in DMSO) lmax (e) = 311
nm (0.300 6 104 L mol21 cm21), 324 (0.383 6 104 L mol21
cm21).
12-(4-Chlorophenyl)-3-Hydroxy-8,12-dihydro-8,10-dimethyl-
9H-naphtho[19,29 : 5,6]pyrano[2,3-d]pyrimidine-9,11-(10H)-
dione (4a, C23H17ClN2O4)
2-Hydroxy-12-(4-trifluoromethylphenyl)-8,12-dihydro-8,10-
dimethyl-9H-naphtho[19,29 : 5,6]pyrano[2,3-d]pyrimidine-9,11-
(10H)-dione (3m, C24H17F3N2O4)
Cream solid; Yield = 83%; M.p.: .300 uC (decom.); Rf 0.35
(petroleum ether : EtOAc, 60 : 40 v/v); 1H NMR (400 MHz,
DMSO-d6): d = 9.80 (s, 1H, OH), 7.83 (d, J = 9.5 Hz, 1H, Ar), 7.76
(d, J = 8.8 Hz, 1H, Ar), 7.48 (d, J = 8.7 Hz, 1H, Ar), 7.33–7.30 (m,
2H, Ar), 7.24–7.21 (m, 2H, Ar), 7.15 (d, J = 2.9 Hz, 1H, Ar), 7.07–
7.04 (m, 1H, Ar), 5.59 (s, 1H, ArC_H_), 3.46 (s, 3H, NC_H_3), 3.13
(s, 3H, NC_H_3) ppm; 13C NMR (100 MHz, DMSO-d6): d = 161.10,
156.70, 152.39, 150.05, 147.32, 146.35, 132.72, 131.94, 130.46,
130.12, 129.60, 127.90, 126.93, 126.63, 125.74, 117.69, 114.17,
113.33, 105.33, 89.41, 35.42, 28.95, 27.76 ppm; IR (KBr) nmax,
cm21 = 3120, 1678, 1650, 1300, 1290; MS (ESI) m/z Calcd. for
White solid; Yield = 85%; M.p.: .300 uC (decom.); Rf 0.35
(petroleum ether : EtOAc, 60 : 40 v/v); 1H NMR (400 MHz,
DMSO-d6): d = 9.98 (s, 1H, OH), 7.87 (d, J = 8.7 Hz, 1H, Ar), 7.79
(d, J = 8.8 Hz, 1H, Ar), 7.59 (d, J = 8.7 Hz, 2H, Ar), 7.51 (d, J = 8.0
Hz, 2H, Ar), 7.36 (d, J = 8.8 Hz, 1H, Ar), 7.13 (s, 1H, Ar), 7.01 (d,
1,2J = 2.2 Hz, 1,3J = 8.8 Hz, 1H, Ar), 5.51 (s, 1H, ArC_H_), 3.47 (s,
3H, NC_H_3), 3.13 (s, 3H, NC_H_3); 13C NMR (100 MHz, DMSO-
d6): d = 161.13, 156.80, 152.44, 150.08, 148.53, 147.35, 131.97,
130.52, 129.71, 129.08, 125.78, 125.20, 117.73, 114.08, 113.40,
105.32, 89.31, 35.63, 28.99, 27.78 ppm; IR (KBr) nmax, cm21
=
3300, 1660, 1629, 1427, 1210 ppm; MS (ESI) m/z Calcd. for
C24H17F3N2O4: 454.11, Found: 455.19 [M+ + H]; Anal. Calcd. for
C24H17F3N2O4: C, 63.44; H, 3.77; N, 6.16; Found: C, 63.48; H,
3.74; N, 6.13; UV (2 6 1024 M solution in DMSO) lmax (e) : 313
nm (0.284 6 104 L mol21 cm21), 325 (0.356 6 104 L mol21
cm21).
C +
23H17ClN2O4: 420.09, Found: 421.11 [M+ + H], 423.11 [M+
H+2]; Anal. Calcd. for C23H17ClN2O4: C, 65.64; H, 4.07; N, 6.66;
Found: C, 65.62; H, 4.06; N, 6.65; UV (2 6 1024 M solution in
DMSO) lmax (e) = 336 nm (0.181 6 104 L mol21 cm21), 350
(0.208 6 104 L mol21 cm21).
3-Hydroxy-12-(4-nitrophenyl)-8,12-dihydro-8,10-dimethyl-
9H-naphtho[19,29 : 5,6]pyrano[2,3-d]pyrimidine-9,11-(10H)-
dione (4b, C23H17N3O6)
2-Hydroxy-12-phenyl-8,12-dihydro-8,10-dimethyl-
9H-naphtho[19,29 : 5,6]pyrano[2,3-d]pyrimidine-9,11-(10H)-
dione (3n, C23H18N2O4)
White solid; Yield = 85%; M.p.: .300 uC (decom.); 1H NMR
(400 MHz, DMSO-d6): d = 9.94 (s, 1H, OH), 7.84 (d, J = 8.7 Hz,
1H, Ar), 7.78 (d, J = 9.5 Hz, 1H, Ar), 7.34 (d, J = 8.7 Hz, 1H, Ar),
7.29 (d, J = 7.3 Hz, 2H, Ar), 7.21–7.17 (m, 3H, Ar), 7.10–7.06 (m,
1H, Ar), 6.99 (dd, 1,2J = 2.2 Hz, 1,3J = 8.8 Hz, 1H, Ar), 5.41 (s, 1H,
ArC_H_), 3.47 (s, 3H, NC_H_3), 3.14 (s, 3H, NC_H_3) ppm; 13C NMR
(100 MHz, DMSO-d6): d = 161.14, 156.63, 152.31, 150.11,
Yellow solid; Yield = 89%; M.p.: .300 uC (decom.); Rf 0.35
(petroleum ether : EtOAc, 60 : 40 v/v); 1H NMR (400 MHz,
DMSO): d = 9.81 (s, 1H, OH), 8.05 (d, J = 8.7 Hz, 2H, Ar), 7.82–
7.76 (m, 2H, Ar), 7.60 (d, J = 8.8 Hz, 2H, Ar), 7.50 (d, J = 8.8 Hz,
1H, Ar), 7.15–7.14 (m, 1H, Ar), 7.05–7.03 (m, 1H, Ar), 5.74 (s,
1H, ArC_H_), 3.47 (s, 3H, NC_H_3), 3.12 (s, 3H, NC_H_3) ppm; 13C
NMR (100 MHz, DMSO-d6): d = 161.04, 155.05, 152.52, 151.70,
150.04, 146.02, 144.67, 133.12, 129.57, 128.24, 125.11, 123.96,
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123.36, 119.75, 117.13, 115.61, 110.07, 88.76, 35.59, 28.95,
27.72 ppm; IR (KBr) nmax, cm21 = 3277, 1670, 1641, 1525, 1348,
1230; MS (ESI) m/z Calcd. for C23H17N3O6: 431.11 Found:
432.18 [M+ + H]; Anal. Calcd. for C23H17N3O6: C, 64.04; H, 3.97;
12-(4-Trifluoromethylphenyl)-8,12-dihydro-8,10-dimethyl-
9H-naphtho[19,29 : 5,6]pyrano[2,3-d]pyrimidine-9,11-(10H)-
dione (5d, C24H17F3N2O3)
White solid; Yield = 78%; M.p.: 268–270 uC; Rf 0.40 (petroleum
ether : EtOAc, 70 : 30 v/v); 1H NMR (400 MHz, CDCl3): d =
7.87–7.81 (m, 3H, Ar), 7.48–7.39 (m, 7H, Ar), 5.84 (s, 1H,
ArC_H_), 3.59 (s, 3H, NC_H_3), 3.31 (s, 3H, NC_H_3) ppm; 13C NMR
(100 MHz, CDCl3): d = 161.86, 152.38, 150.53, 147.58, 147.19,
131.79, 130.65, 129.96, 129.07, 128.75, 128.64, 128.61, 127.68,
125.70, 125.45, 125.42, 123.61, 116.40, 116.31, 90.64, 35.91,
29.09, 28.23; IR (KBr) nmax, cm21 = 2978, 1670, 1635, 1340,
1210; MS (ESI) m/z Calcd. for C24H17F3N2O3: 438.12, Found:
439.18 [M+ + H]; UV (2 6 1024 M solution in DMSO) lmax (e) =
313 nm (0.082 6 104 L mol21 cm21), 327 (0.059 6 104 L mol21
cm21).
N, 9.74; Found: C, 64.02; H, 3.96; N, 9.75; UV (2 6 1024
M
solution in DMSO) lmax (e) = 336 nm (0.231 6 104 L mol21
cm21), 348 (0.366 6 104 L mol21 cm21).
12-(4-Chlorophenyl)-8,12-dihydro-8,10-dimethyl-
9H-naphtho[19,29 : 5,6]pyrano[2,3-d]pyrimidine-9,11-(10H)-
dione (5a, C23H17ClN2O3)
White solid; Yield = 84%; M.p.: 264–266 uC (Lit. 274–276 uC)14a
;
1H NMR (400 MHz, CDCl3): d = 7.86–7.80 (m, 3H, Ar), 7.47–7.36
(m, 3H, Ar), 7.29 (d, J = 8.0 Hz, 2H, Ar), 7.15 (d, J = 8.0 Hz, 2H,
Ar), 5.76 (s, 1H, ArC_H_), 3.58 (s, 3H, NC_H_3), 3.31 (s, 3H, NC_H_3)
ppm; 13C NMR (100 MHz, CDCl3): d = 161.91, 152.23, 150.56,
147.11, 142.30, 132.51, 131.77, 130.71, 129.77, 129.62, 128.58,
127.58, 125.62, 123.73, 116.75, 116.29, 90.95, 35.47, 29.06,
28.21 ppm; IR (KBr) nmax, cm21 = 2960, 1668, 1620, 1358, 1203;
MS (ESI) m/z Calcd. for C23H17ClN2O3: 404.09, Found: 405.10
[M+ + H], 407.10 [M+ + H+2]; UV (2 6 1024 M solution in
DMSO) lmax (e) = 314 nm (0.088 6 104 L mol21 cm21), 327
(0.067 6 104 L mol21 cm21).
10-(4-Chlorophenyl)-6,8-dimethyl-6,10-dihydro-5-oxa-6,8-
diazaanthra[2,3-d][1,3] dioxole-7,9-dione (6a, C20H15ClN2O5)
White solid; Yield = 75%; M.p.: 240–242 uC (Lit. 254–255 uC)14c
;
1H NMR (400 MHz, CDCl3): d = 7.24–7.15 (m, 4H, Ar), 6.65 (s,
1H, Ar), 6.45 (s, 1H, Ar), 5.94 (s, 1H, 1H of OC_H_2), 5.91 (s, 1H,
1H of OC_H_2), 4.98 (s, 1H, ArC_H_), 3.52 (s, 3H, NC_H_3), 3.26 (s,
3H, NC_H_3) ppm; 13C NMR (100 MHz, CDCl3): d 161.85, 152.57,
150.62, 147.36, 145.66, 143.57, 142.99, 132.65, 129.24, 128.67,
116.09, 108.02, 101.92, 98.08, 89.55, 38.60, 29.04, 29.10 ppm;
IR (KBr) nmax, cm21 = 2960, 1668, 1620, 1358, 1203; MS (ESI) m/
z Calcd. for C20H15ClN2O5: 398.07, Found: 399.10 [M+ + H],
401.10 [M+ + H+2]; UV (2 6 1024 M solution in DMSO) lmax (e)
12-(4-Nitrophenyl)-8,12-dihydro-8,10-dimethyl-
9H-naphtho[19,29 : 5,6]pyrano[2,3-d]pyrimidine-9,11-(10H)-
dione (5b, C23H17N3O5)
Cream solid; Yield = 86%; M.p.: 280–288 uC (Lit. 291–293
uC)14a; 1H NMR (400 MHz, CDCl3): d 8.07 (d, J = 8.7 Hz, 2H, Ar),
7.91–7.80 (m, 3H, Ar), 7.55 (d, J = 8.7 Hz, 2H, Ar), 7.50–7.43 (m,
3H, Ar), 5.91 (s, 1H, ArC_H_), 3.63 (s, 3H, NC_H_3), 3.31 (s, 3H,
NC_H_3) ppm; 13C NMR (100 MHz, CDCl3): d d 161.81, 151.21,
150.62, 147.18, 142.42, 133.50, 131.72, 131.70, 129.77, 129.68,
128.58, 126.58, 125.61, 123.71, 116.78, 116.32, 90.98, 35.41,
29.06, 28.26 ppm; IR (KBr) nmax, cm21 = 2964, 1670, 1632, 1350,
1230; MS (ESI) m/z Calcd. for C23H17N3O5: 415.12, Found:
416.18 [M+ + H]; UV (2 6 1024 M solution in DMSO) lmax (e) =
313 nm (0.085 6 104 L mol21 cm21), 325 (0.072 6 104 L mol21
cm21).
= 312 nm (0.062 6 104 L mol21 cm21), 325 (0.049 6 104
L
mol21 cm21).
10-(3-Chlorophenyl)-6,8-dimethyl-6,10-dihydro-5-oxa-6,8-
diazaanthra[2,3-d][1,3]dioxole-7,9-dione (6b, C20H15ClN2O5)
White solid; Yield = 72%; M.p.: 228–230 uC; Rf 0.50 (petroleum
ether : EtOAc, 80 : 20 v/v); 1H NMR (400 MHz, CDCl3): d =
7.24–7.11 (m, 4H, Ar), 6.66 (s, 1H, Ar), 6.46 (s, 1H, Ar), 5.95 (s,
1H, 1H of OC_H_2), 5.92 (s, 1H, 1H of OC_H_2), 4.98 (s, 1H,
ArC_H_), 3.53 (s, 3H, NC_H_3), 3.26 (s, 3H, NC_H_3) ppm; 13C NMR
(100 MHz, CDCl3): d = 161.82, 152.68, 150.65, 147.43, 147.02,
145.69, 142.99, 134.42, 129.72, 127.90, 127.17, 126.27, 115.92,
108.03, 101.94, 98.15, 89.36, 38.94, 29.07, 28.13 ppm; (KBr)
nmax, cm21 = 2921, 1706, 1648, 1490, 1210; MS (ESI) m/z Calcd.
for C20H15ClN2O5: 398.07, Found: 399.12[M+ + H], 401.12 [M+ +
H+2]; Anal. Calcd. for C20H15ClN2O5: C, 60.23; H, 3.79; N, 7.02;
Found: C, 60.27; H, 3.75; N, 7.05; UV (2 6 1024 M solution in
DMSO) lmax (e) = 312 nm (0.055 6 104 L mol21 cm21), 327
(0.048 6 104 L mol21 cm21).
12-(4-Fluorolphenyl)-8,12-dihydro-8,10-dimethyl-9H-naphtho
[19,29 : 5,6]pyrano[2,3-d]pyrimidine-9,11-(10H)-dione (5c,
C23H17FN2O3)
White solid; Yield = 84%; M.p.: 294–296 uC (Lit. 305–307 uC)14b
;
1H NMR (400 MHz, CDCl3): d = 7.88–7.80 (m, 3H, Ar), 7.45–7.37
(m, 3H, Ar), 7.32–7.29 (m, 2H, Ar), 6.88–6.84 (m, 2H, Ar), 5.78
(s, 1H, ArC_H_), 3.59 (s, 3H, NC_H_3), 3.32 (s, 3H, NC_H_3); 13C
NMR (100 MHz, CDCl3): d = 161.96, 152.20, 150.60, 147.11,
139.63, 131.79, 130.75, 129.82, 129.74, 129.68, 128.58, 127.53,
125.59, 123.81, 117.08, 116.31, 115.36, 91.23, 35.30, 29.06,
28.22; IR (KBr) nmax, cm21 = 2958, 1668, 1635, 1346, 1208; MS
(ESI) m/z Calcd. for C23H17FN2O3: 388.12, Found: 389.18 [M+ +
H]; UV (2 6 1024 M solution in DMSO) lmax (e) = 313 nm (0.085
6 104 L mol21 cm21), 327 (0.049 6 104 L mol21 cm21).
10-(4-Methylphenyl)-6,8-dimethyl-6,10-dihydro-5-oxa-6,8-
diazaanthra[2,3-d][1,3]dioxole-7,9-dione (6c, C21H18N2O5)
White solid; Yield = 80%; M.p.: 236–238 uC; 1H NMR (400 MHz,
CDCl3): d 7.13 (d, J = 5.8 Hz, 2H, Ar), 7.06 (d, J = 6.6 Hz, 2H, Ar),
6.65 (s, 1H, Ar), 6.50 (s, 1H, Ar), 5.93 (s, 1H, 1H of OC_H_2), 5.89
(s, 1H, 1H of OC_H_2), 4.98 (s, 1H, ArC_H_), 3.53 (s, 3H, NC_H_3),
3.26 (s, 3H, NC_H_3), 2.25(s, 3H, CH3) ppm; IR (KBr) nmax, cm21
= 2910, 1708, 1662, 1476, 1215; MS (ESI) m/z Calcd. for
C21H18N2O5: 378.12, Found: 379.18 [M+ + H]; UV (2 6 1024
M
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solution in DMSO) lmax (e) = 313 nm (0.068 6 104 L mol21
cm21), 327 (0.054 6 104 L mol21 cm21).
12-(4-Trifluoromethylphenyl)-2-hydroxy-9,9-dimethyl-8,9,
10,12-tetrahydrobenzo[a]xanthen-11-one (7b, C26H21F3O3)
White solid; Yield = 84%; M.p. .300 uC; Rf 0.35 (petroleum
ether : EtOAc, 60 : 40 v/v); H NMR (300 MHz, DMSO-d6): d =
10-(4-Fluorophenyl)-6,8-dimethyl-6,10-dihydro-5-oxa-6,8-
diazaanthra[2,3-d][1,3]dioxole-7,9-dione (6d, C20H15FN2O5)
1
9.87 (s, 1H, OH), 7.71–7.76 (m, 2H, Ar), 7.24–7.18 (m, 4H, Ar),
6.98–7.03 (m, 3H, Ar), 5.38 (s, 1H, ArC_H_), 2.67 and 2.55 (AB
system, J = 17.8 Hz, 2H, CHa.HbCMe2), 2.32 (d, J = 16.2 Hz, 1H
of C_H_2CO), 2.11 (d, J = 16.2 Hz, 1H of C_H_2CO), 1.01 (s, 3H,
CM_e_), 0.90 (s, 3H, CM_e_) ppm; 13C NMR (300 MHz, DMSO-d6):
d = 195.91, 163.93, 158.80, 156.41, 147.61, 140.80, 131.37,
130.21, 129.82, 128.84, 125.46, 117.13, 115.10, 114.93, 113.50,
113.11, 105.08, 50.03, 40.31, 33.42, 31.81, 28.71, 26.13 ppm; IR
(KBr) nmax, cm21 = 3184, 1629, 1593, 1381, 1236; MS (ESI) m/z
Calcd. for C26H21F3O3: 438.14 Found: 439.18 [M+ + H]; Anal.
Calcd. for C26H21F3O3: C, 71.23; H, 4.83; Found: C, 71.20; H,
4.82; UV (2 6 1024 M solution in DMSO) lmax (e) = 325 nm
(0.268 6 104 L mol21 cm21), 337 (0.228 6 104 L mol21 cm21).
1
White solid; Yield = 72%; M.p.: 220–222 uC (decom.); H NMR
(400 MHz, CDCl3): d = 7.20–7.17 (m, 2H, Ar), 6.94–6.89 (m, 2H, Ar),
6.65 (s, 1H, Ar), 6.46 (s, 1H, Ar), 5.94 (s, 1H, 1H of OC_H_2), 5.91 (s,
1H, 1H of OC_H_2), 5.00 (s, 1H, ArC_H_), 3.52 (s, 3H, NC_H_3), 3.26 (s,
3H, NC_H_3) ppm; 13C NMR (100 MHz, CDCl3): d = 161.89, 152.52,
150.66, 147.29, 145.64, 143.07, 140.90, 129.41, 116.46, 115.20,
108.16, 101.90, 98.06, 89.84, 38.52, 29.06, 28.13 ppm; IR (KBr)
nmax, cm21 = 2921, 1706, 1648, 1490, 1210; MS (ESI) m/z Calcd. for
C20H15FN2O5: 382.10, Found: 383.20 [M+ + H]; UV (2 6 1024
M
solution in DMSO) lmax (e) : 314 nm (0.085 6 104 L mol21 cm21),
325 (0.060 6 104 L mol21 cm21).
10-(4-Nitrophenyl)-6,8-dimethyl-6,10-dihydro-5-oxa-6,8-diaza
anthra[2,3-d][1,3]dioxole-7,9-dione (6e, C20H15N3O7)
12-(4-Fluorophenyl)-2-hydroxy-9,9-dimethyl-8,9,10,12-
White solid; Yield = 75%; M.p.: 240–242 uC (decom.); 1H NMR (400
MHz, CDCl3): d = 7.30–7.27 (m, 2H, Ar), 7.00–6.98 (m, 2H, Ar), 6.67
(s, 1H, Ar), 6.54 (s, 1H, Ar), 5.98 (s, 1H, 1H of OC_H_2), 5.94 (s, 1H, 1H
of OC_H_2), 5.09 (s, 1H, ArC_H_), 3.52 (s, 3H, NC_H_3), 3.26 (s, 3H,
NC_H_3) ppm; IR (KBr) nmax, cm21 = 2911, 1708, 1662, 1476, 1214;
MS (ESI) m/z Calcd. for C20H15N3O7: 409.09, Found: 410.10 [M+ +
H]; UV (2 6 1024 M solution in DMSO) lmax (e) = 313 nm (0.082 6
104 L mol21 cm21), 327 (0.051 6 104 L mol21 cm21).
tetrahydrobenzo[a]xanthen-11-one (7c, C25H21FO3)
White solid; Yield = 82%; M.p. 278–280 uC (decom.) (Lit. 276–
278 uC)14d; 1H NMR (300 MHz, DMSO-d6): d = 9.88 (s, 1H, OH),
7.72–7.77 (m, 2H, Ar), 7.27–7.16 (m, 4H, Ar), 6.95–7.05 (m, 3H,
Ar), 5.35 (s, 1H, ArC_H_), 2.68 and 2.57 (AB system, J = 17.4 Hz,
2H, CHa.HbCMe2), 2.34 (d, J = 16.2 Hz, 1H of C_H_2CO), 2.13 (d, J
= 16.2 Hz, 1H of C_H_2CO), 1.03 (s, 3H, CM_e_), 0.85 (s, 3H, CM_e_)
ppm; 13C NMR (300 MHz, DMSO-d6): d = 195.92, 163.90,
158.83, 156.47, 147.64, 140.81, 132.37, 130.24, 129.84, 128.88,
125.47, 117.14, 115.11, 114.96, 113.51, 113.10, 105.08, 50.03,
6,8-Dimethyl-10-phenyl-6,10-dihydro-5-oxa-6,8-diazaanthra
[2,3-d][1,3]dioxole-7,9-dione (6f, C20H16N2O5)
40.33, 33.43, 31.83, 28.77, 26.14 ppm; IR (KBr) nmax, cm21
3184, 1629, 1593, 1381, 1236; MS (ESI) m/z Calcd. For
=
White solid; Yield = 75%; M.p.: 220–222 uC; 1H NMR (400 MHz,
CDCl3): d = 7.25–7.22 (m, 4H, Ar), 7.17–7.16 (m, 1H, Ar), 6.66 (s,
1H, Ar), 6.50 (s, 1H, Ar), 5.94 (d, J = 1.44, 1H, 1H of OC_H_2), 5.90
(d, J = 1.48, 1H, 1H of OC_H_2), 5.01 (s, 1H, ArC_H_), 3.54 (s, 3H,
NC_H_3), 3.27 (s, 3H, NC_H_3) ppm; 13C NMR (100 MHz, CDCl3): d =
161.86, 152.55, 150.70, 147.15, 145.54, 145.06, 143.05, 128.53,
127.80, 126.86, 116.74, 108.16, 101.81, 97.94, 89.99, 39.13, 29.00,
28.08 ppm; IR (KBr) nmax, cm21 = 2892, 1702, 1667, 1482, 1210;
MS (ESI) m/z Calcd. For C20H16N2O5: 364.11, Found: 365.20 [M+ +
H]; UV (2 6 1024 M solution in DMSO) lmax (e) = 315 nm (0.065
6 104 L mol21 cm21), 324 (0.048 6 104 L mol21 cm21).
C25H21FO3: 388.14 Found: 389. 20 [M+ + H]; UV (2 6 1024
M
solution in DMSO) lmax (e) = 325 nm (0.287 6 104 L mol21
cm21), 337 (0.256 6 104 L mol21 cm21).
2-Hydroxy-9,9-dimethyl-12-(4-nitrophenyl)-8,9,10,12-
tetrahydrobenzo[a]xanthen-11-one (7d, C25H21NO5)
Light yellow solid; Yield = 87%; M.p. 288–290 uC (decom.) (Lit.
288–290 uC)14d; 1H NMR (300 MHz, CDCl3): d = 9.29 (s, 1H, OH),
8.03 (d, J = 8.1 Hz, 2H, Ar), 7.70–7.63 (m, 2H, Ar), 7.56–7.53 (d, J =
8.4 Hz, 2H, Ar), 7.19 (s, 1H, Ar), 7.14 (d, J = 8.7 Hz, 1H, Ar), 7.03
(d, J = 8.7 Hz, 1H, Ar), 5.63 (s, 1H, ArC_H_), 2.59 (s, 2H, C_H_2CMe2),
2.35 (d, J = 16.2 Hz, 1H of C_H_2CO), 2.24 (d, J = 16.2 Hz, 1H of
C_H_2CO), 1.13 (s, 3H, CM_e_), 0.94 (s, 3H, CM_e_) ppm; 13C NMR
(300 MHz, DMSO-d6): d = 195.84, 164.49, 158.07, 151.96, 147.50,
145.68, 132.52, 130.18, 129.31, 125.06, 123.23, 117.94, 113.77,
112.93, 112.13, 104.90, 49.94, 40.32, 34.42, 31.85, 28.74, 26.20
ppm; IR (KBr) nmax, cm21 = 3196, 1632, 1594, 1382, 1221; MS
(ESI): m/z Calcd. For C25H21NO5: 415.14 Found: 416.14 [M+ + H];
UV (2 6 1024 M solution in DMSO) lmax (e) = 328 nm (0.438 6
104 L mol21 cm21), 337 (0.392 6 104 L mol21 cm21).
12-(4-Chlorophenyl)-2-hydroxy-9,9-dimethyl-8,9,10,12-tetra
hydrobenzo[a]xanthen-11-one (7a, C25H21ClO3)
White solid; Yield = 86%; M.p. .300 uC (decom.) (Lit. .300
uC)14d; 1H NMR (300 MHz, CDCl3): d = 9.29 (s, 1H, OH), 7.67–7.62
(m, 2H, Ar), 7.31–7.24 (m, 3H, Ar), 7.14–7.09 (m, 3H, Ar), 7.02–
6.99 (m, 1H, Ar), 5.50 (s, 1H, ArC_H_), 2.57 (s, 2H, C_H_2CMe2), 2.33
(d, J = 16.2 Hz, 1H of C_H_2CO), 2.24 (d, J = 16.2 Hz, 1H of C_H_2CO),
1.12 (s, 3H, CM_e_), 0.95 (s, 3H, CM_e_) ppm; IR (KBr) nmax, cm21
=
3194, 1631, 1594, 1381, 1235; 13C NMR (300 MHz, CDCl3): d
199.4, 166.18, 156.30, 147.96, 142.95, 132.87, 132.04, 130.39,
129.87, 129.04, 128.42, 126.49, 117.39, 115.45, 113.87, 113.81,
05.86, 50.40, 41.50, 34.45, 32.51, 29.32, 27.05; MS (ESI) m/z Calcd.
For C25H21ClO3: 404.12 Found: 405.16 [M+ + H], 407.16 [M+ +
H+2]; UV (2 6 1024 M solution in DMSO) lmax (e) = 325 nm (0.370
6 104 L mol21 cm21), 337 (0.327 6 104 L mol21 cm21).
2-Hydroxy-12-(4-methoxyphenyl)-9,9-dimethyl-8,9,10,12-
tetrahydrobenzo[a]xanthen-11-one (7e, C26H24O4)
White solid; Yield = 85%; M.p. 282–284 uC (decom.) (Lit. 280–
1
282 uC)14d; H NMR (300 MHz, CDCl3): d = 9.24 (s, 1H, OH),
2
3
7.64 (dd, J = 1.5 Hz, J = 8.7 Hz, 2H, Ar), 7.33 (s, 1H, Ar), 7.27
(d, J = 8.7 Hz, 2H, Ar), 7.11 (d, J = 8.7 Hz, 1H, Ar), 7.01 (dd, 2J =
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2.1 Hz, 3J = 8.7 Hz, 1H, Ar), 6.70 (d, J = 8.7 Hz, 2H, Ar), 5.47 (s,
1H, ArC_H_), 3.67 (s, 3H, OC_H_3), 2.56 (s, 2H of C_H_2CMe2), 2.32
(d, J = 16.2 Hz, 1H of CH2CO), 2.23 (d, J = 16.2 Hz, 1H of
C_H_2CO), 1.11 (s, 3H, C_M_e_), 0.96 (s, 3H, C_M_e_) ppm; IR (KBr)
nmax, cm21 = 3190, 1630, 1594, 1380, 1227; 13C NMR (300 MHz,
DMSO-d6): d = 195.93, 163.60, 157.41, 156.33, 147.57, 136.80,
132.46, 130.15, 128.99, 128.57, 125.45, 117.04, 115.68, 113.51,
113.46, 113.42, 105.22, 54.84, 50.09, 40.32, 33.21, 31.83, 28.81,
26.22; MS (ESI): m/z Calcd. For C26H24O4: 400.17 Found: 401.18
[M+ + H]; UV (2 6 1024 M solution in DMSO) lmax (e) = 325 nm
(0.254 6 104 L mol21 cm21), 337 (0.221 6 104 L mol21 cm21).
DMSO-d6): d = 9.88 (s, 1H, OH), 7.78–7.73 (m, 2H, Ar), 7.27–
7.16 (m, 4H, Ar), 7.05–6.95 (m, 3H, Ar), 5.38 (s, 1H, CH), 2.74–
2.70 (m, 2H, CH2), 2.38–2.31 (m, 2H, CH2), 2.01–1.96 (m, 1H of
C_H_2), 1.85–1.83 (m, 1H of C_H_2) ppm; 13C NMR (300 MHz,
DMSO-d6): d = 196.02, 163.72, 156.32, 148.10, 147.54, 137.25,
132,52, 130.16, 128.57, 125.44, 120.05, 117.06, 115.66, 113.51,
112.23, 111.48, 105.27, 33.54, 31.48, 28.85, 26.14 ppm; IR (KBr)
nmax, cm21 = 3186, 1626, 1594, 1384, 1233; MS (ESI): m/z Calcd.
For C24H17F3O3: 410.11 Found: 411.18 [M+ + H]; Anal. Calcd.
for C24H17F3O3: C, 70.24; H, 4.18; Found: C, 70.28; H, 4.16; UV
(2 6 1024 M solution in DMSO) lmax (e) = 326 nm (0.539 6 104
L mol21 cm21), 338 (0.487 6 104 L mol21 cm21).
12-(4-Chlorophenyl)-2-hydroxy-8,9,10,12-
tetrahydrobenzo[a]xanthen-11-one (8a, C23H17ClO3)
2-Hydroxy-12-(4-methylphenyl)-8,9,10,12-
1
White solid; Yield = 83%; M.p. .300 uC (Lit. .300 uC)14d; H
tetrahydrobenzo[a]xanthen-11-one (8e, C24H20O3)
NMR (300 MHz, DMSO-d6): d = 9.73 (s, 1H, OH), 7.67–7.62 (m,
2H, Ar),7.68–7.12 (m, 7H, Ar), 5.25 (s, 1H, ArC_H_), 2.69–2.63 (m,
2H, C_H_2), 2.42–2.24 (m, 2H, C_H_2), 1.94–1.89 (m, 1H of C_H_2),
1.76–1.79 (m, 1H of C_H_2) ppm; IR (KBr) nmax, cm21 = 3174,
1629, 1595, 1380, 1227, 1196; MS (ESI): m/z Calcd. For
White solid; Yield = 84%; M.p. 286–288 uC (decom.) (Lit. 286–
288 uC)14d; 1H NMR (300 MHz, DMSO-d6): d = 9.86 (s, 1H, OH),
7.76–7.72 (m, 2H, Ar), 7.20–7.10 (m, 4H, Ar), 7.00–6.94 (m, 3H,
Ar); 5.32 (s, 1H, ArC_H_), 2.73–2.71 (m, 2H, C_H_2), 2.40–2.24 (m,
2H, C_H_2), 2.16 (s, 3H, ArC_H_3), 2.02–1.96 (m, 1H of C_H_2), 1.84–
1.82 (m, 1H of C_H_2); ; 13C NMR (300 MHz, DMSO-d6): d =
196.15, 165.57, 156.32, 147.62, 142.06, 135.20, 132.46, 130.16,
128.71, 128.61, 127.95, 125.42, 117.05, 115.57, 114.64, 113.47,
105.18, 36.41, 33.62, 26.89, 20.46, 19.94 ppm; IR (KBr) nmax,
cm21: 3212, 1630, 1596, 1380, 1229, 1196; MS (ESI): m/z Calcd.
For C24H20O3: 356.14 Found: 357.18 [M+ + H]; UV (2 6 1024 M
solution in DMSO) lmax (e) = 324 nm (0.428 6 104 L mol21
cm21), 335 (0.318 6 104 L mol21 cm21).
C23H17ClO3: 376.09 Found: 377.10 [M+ + H]; 379.10 [M+
+
H+2]; UV (2 6 1024 M solution in DMSO) lmax (e) = 325 nm
(0.561 6 104 L mol21 cm21), 337 (0.634 6 104 L mol21 cm21).
2-Hydroxy-12-(4-nitrophenyl)-8,9,10,12-
tetrahydrobenzo[a]xanthen-11-one (8b, C23H17NO5)
Light yellow solid; Yield = 86%; M.p. .300 uC (decom.) (Lit. .300
uC)14d; 1H NMR (300 MHz, DMSO-d6): d = 9.94 (s, 1H, OH), 8.10 (d,
J = 8.4 Hz, 2H, Ar), 7.82 (dd, 2J = 9.0 Hz, , 3J = 13.2 Hz, 2H, Ar), 7.52
(d, J = 8.4 Hz, 2H), 7.24 (d, J = 8.7 Hz, 2H), 7.12 (s, 1H, Ar), 5.51 (s,
1H, ArC_H_), 2.74–2.71 (m, 2H, C_H_2), 2.39–2.32 (m, 2H, C_H_2), 2.01–
1.97 (m, 1H of C_H_2), 1.85–1.83 (m, 1H of C_H_2) ppm; 13C NMR
(300 MHz, DMSO-d6): d = 196.20, 166.38, 156.63, 152.22, 147.66,
145.87, 132.28, 130.36, 129.43, 129.38, 125.47, 123.45, 117.26,
114.00, 113.51, 113.30, 104.91, 36.31, 34.38, 26.97, 19.84 ppm; IR
(KBr) nmax, cm21 = 3197, 1630, 1594, 1344, 1228; MS (ESI): m/z
Calcd. For C23H17NO5: 387.11 Found: 388.11 [M+ + H]; UV (2 6
1024 M solution in DMSO) lmax (e) = 325 nm (0.592 6 104 L mol21
cm21), 337 (0.627 6 104 L mol21 cm21).
Conclusions
In conclusion, we have developed a simple, one-pot three
component facile syntheses of diverse naphthopyranopyrimi-
dines, diazaanthra[2,3-d][1,3]dioxole-7,9-dione and tetrahydro-
benzo[a]xanthen-11-ones in PEG-400 catalyzed by alum.
Simple work up procedure, general applicability, ambient
conditions and recyclability of the reaction media PEG-400
makes this protocol eco-friendly and distinctly superior to
many other methods reported earlier. Moreover, compounds
3a, 3d, 3i, 3j, 3k, 3l, 3o, 4a, 4b and 5b displayed very good
antioxidant activity compared to the standard.
2-Hydroxy-12-phenyl-8,9,10,12-tetrahydrobenzo[a]xanthen-11-
one (8c, C23H18O3)
White solid; Yield = 89%; M.p. .300 uC (decom.) (Lit. .300 uC)14d
;
1H NMR (300 MHz, DMSO-d6): d = 9.86 (s, 1H, OH), 7.72–7.76 (m,
2H, Ar), 7.25–7.16 (m, 6H, Ar), 7.08–7.04 (m, 1H, Ar), 6.97 (d, J = 9
Hz, 1H, Ar), 5.37 (s, 1H, ArC_H_), 2.71–2.69 (m, 2H, C_H_2), 2.41–2.25
(m, 2H, C_H_2), 1.99–1.94 (m, 1H of C_H_2), 1.83–1.79 (m, 1H of C_H_2)
ppm; 13C NMR (300 MHz, DMSO-d6): d = 196.14, 165.76, 156.38,
147.70, 144.97, 132.46, 130.18, 128.70, 128.15, 128.07, 126.13,
125.45, 117.10, 115.45, 114.57, 113.48, 105.13, 36.40, 34.06, 26.90,
19.91 ppm; IR (KBr) nmax, cm21 = 3200, 1625, 1593, 1382, 1230,
1194; MS (ESI): m/z Calcd. For C23H18O3: 342.13 Found: 343.18
[M+ + H]; UV (2 6 1024 M solution in DMSO) lmax (e) = 324 nm
(0.695 6 104 L mol21 cm21), 337 (0.623 6 104 L mol21 cm21).
Acknowledgements
AL thanks University of Delhi for the award of University
Teaching Assistantship. AC and BN thank CSIR, New Delhi for
the grant of Junior/Senior Research Fellowship.
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