An efficient one-pot synthesis of tetrahydrobenzo[a]xanthene-11-one and diazabenzo[a]anthracene-9,11-dione derivatives under solvent free condition

Article abstract of DOI:10.1016/j.tet.2009.06.024

Indium(III) chloride catalyzed one-pot synthesis of 12-aryl/alkyl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-one and 8,10-dimethyl-12-aryl-8,12-dihydro-7-oxa-8,10-diazabenzo[a]anthracene-9,11-dione derivatives have been achieved by three component cycloconde

Full text of DOI:10.1016/j.tet.2009.06.024

Tetrahedron 65 (2009) 7129–7134
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An efficient one-pot synthesis of tetrahydrobenzo[a]xanthene-11-one and
diazabenzo[a]anthracene-9,11-dione derivatives under solvent free condition
*
Ganesh Chandra Nandi, Subhasis Samai, Ram Kumar, M.S. Singh
Department of Chemistry, Faculty of Science, Banaras Hindu University, Varanasi 221005, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Indium(III) chloride catalyzed one-pot synthesis of 12-aryl/alkyl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-
one and 8,10-dimethyl-12-aryl-8,12-dihydro-7-oxa-8,10-diazabenzo[a]anthracene-9,11-dione derivatives
have been achieved by three component cyclocondensation of aldehydes, b-naphthol and cyclic 1,3-di-
carbonyl compounds under solvent free condition in high yields. P2O5 too has been found as an effective
catalyst towards this transformation.
Received 25 March 2009
Received in revised form 4 June 2009
Accepted 8 June 2009
Available online 12 June 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Multicomponent reaction
One-pot synthesis
InCl3
P2O5
Benzoxanthene
Benzoanthracene
1. Introduction
Xanthenes and benzoxanthenes are important biologically ac-
tive heterocyclic compounds, which possess antiviral,10 anti-in-
In the mainstream of current interest, multi-component pro-
cesses have recently gained considerable economic and ecological
interest as they address fundamental principles of synthetic effi-
ciency and reaction design. Multi-component reactions (MCRs)
have been proven to be a very elegant and rapid way to access
complex structures in a single synthetic operation from simple
building blocks and show high atom economy and high selectivity.1
As a one-pot reaction, MCRs generally afford good yields and are
fundamentally different from two-component reactions in several
aspects2 and permitted rapid access to combinatorial libraries of
organic molecules for efficient lead structure identification and
optimization in drug discovery.3 Over the past decade, various
advanced sequential MCRs have been developed where 1,3-dicar-
bonyl derivatives are important synthetic intermediates due to its
multiple functionalities that can be involved either as nucleophilic
or electrophilic species in a large variety of synthetic trans-
formations.4 There versatility and effectiveness as potential multi-
component substrate has been used in various MCRs such as
Hantzsch 1,4-dihydropyridine synthesis,5 Biginelli reaction,6
Schopf’s tropinone synthesis,7 Tietze’s reaction8 and Michael ad-
dition reaction.9
flammatory11 and antibacterial12 activities. These are being utilized
as antagonists for paralyzing action of zoxazolamine13 and in
photodynamic therapy.14 Furthermore, these compounds can be
used as dyes,15 in laser technologies16 and as pH sensitive fluore-
scent materials for visualization of biomolecules.17
It is evident from the recent literature that indium trichloride18
has invoked enormous interest as a green and potential Lewis acid
catalyst to construct carbon-carbon and carbon–heteroatom bonds
in various organic transformations such as Mukaiyama aldol con-
densation,19 Diels–Alder reactions,20 aza-Michael reactions21 and
ring opening reactions of epoxides with nucleophiles.22 It has re-
ceived considerable attention due to its low toxicity, cost effec-
tiveness, air and water compatibility, ease of handling, good
reactivity, experimental simplicity and remarkable ability to sup-
press side reactions in acid sensitive substrates.
The condensation of phenol with aldehyde in the presence of
acid or base catalyst is believed to proceed via ortho-quinone
methide (o-QM) intermediate,23 which has been used in many
tandem processes24 and [4þ2] cycloaddition with variety of dieno-
philes.25 However, with carbon nucleophiles only limited work has
been appeared.26 We have developed an efficient tandem process
that would allow the reaction of o-QM intermediate with carbon
nucleophiles in situ to provide xanthene derivatives under solvent
free and simple reaction conditions. Herein, we are reporting the
reaction of aldehydes, 2-naphthol and cyclic 1,3-dicarbonyl
* Corresponding author. Tel.: þ91 542 6702502; fax: þ91 542 2368127.
E-mail address: mssinghbhu@yahoo.co.in (M.S. Singh).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.06.024

7130
G.C. Nandi et al. / Tetrahedron 65 (2009) 7129–7134
compounds for the formation of tetrahydrobenzo[a]xanthene-11-
one and diazabenzo[a]anthracene-9,11-dione derivatives in pres-
ence of catalytic amount of InCl3 or P2O5 under solvent free con-
ditions (Scheme 1). To the best of our knowledge, this methodology
has not been reported in the literature. These catalysts not only
make the synthetic process clean, safe and inexpensive, but also
afford the products in excellent yield.
condition, the catalytic activity of P2O5 and InCl3 increases and very
less amount of by-product was formed. InCl3 was thus found to be
the catalyst of choice.
A test reaction using 4-nitrobenzaldehyde, 2-naphthol and
dimedone at 120 ꢀC in the absence of solvent and without any
catalyst was performed in order to establish the real effectiveness
of the catalysts. It was found that only 15% conversion to product
was obtained even after 2.5 h of heating. To optimize the catalyst
loading, 5 mol %,10 mol %,15 mol % and 25 mol % of InCl3 was tested
but the yields were not good. A 30 mol % loading of InCl3 was suf-
ficient to push the reaction forward and higher amounts of catalyst
did not increase the yields significantly. The best results were
obtained when the reactions were carried out with 30 mol % of
InCl3 at 120 ꢀC. To explore the generality of the reaction, we ex-
tended our study using InCl3 (30 mol %) and P2O5 (20 mol %) as
catalysts separately under solvent free condition with different al-
iphatic as well as aromatic aldehydes to prepare a series of ben-
zo[a]xanthene-11-one derivatives (Table 1). Various aromatic
aldehydes containing electron-withdrawing and electron-donating
substituent at ortho, meta or para-positions show equal ease to-
wards the product formation in good to high yields. Interestingly,
aliphatic aldehydes also gave the expected xanthene-11-one de-
rivatives in good yields.
O
R1
O
O
O
InCl3
or
3
or
O
O
5a-r
OH
R1-CHO
+
P2O5
+
or
solvent free
120 °C
Me
O
R1
O
1
N
2
Me
O
N
Me
4
N
O
N
Me
6a-i
Scheme 1. InCl3 and P2O5 catalyzed condensation of aldehydes, b-naphthol and cyclic
1,3-dicarbonyl compounds.
2. Result and discussion
Table 1
InCl3 and P2O5 catalyzed condensation of 2-naphthol, aldehyde and 1,3-dicarbonyl
compound to give 5 and 6
Xanthenes and its derivatives are an important structural motif
in biologically relevant compounds and pharmaceuticals. Pre-
viously tetrahydrobenzo[a]xanthenes have been synthesized under
reflux for 4–5 h in dichloromethane or 1,2-dichloroethane in the
presence of acid catalysts such as BF3$Et2O,27 silica supported
Entry
R1
Diketone
Method A (InCl3)a
Method B (P2O5)a
Time (min)/
yieldb (%)
Time (min)/
yieldb (%)
29
NaHSO4,28 Sr(OTf)2 and TBAF.30 These synthetic methods affor-
5a
5b
5c
5d
5e
5f
5g
5h
5i
C6H5
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
30/84
30/88
30/80
55/81
45/76
35/87
30/80
60/83
25/85
65/70
60/68
35/76
30/73
50/82
55/80
50/74
60/73
75/70
75/65
70/63
60/68
60/70
65/65
70/67
65/69
65/70
60/72
40/76
36/80
45/77
60/75
55/71
40/80
40/76
65/74
30/78
70/68
65/64
40/71
35/70
60/73
55/74
55/71
65/62
80/62
80/58
70/58
65/60
60/62
65/61
75/62
70/65
65/62
65/67
p-NO2C6H4
m-NO2C6H4
o-NO2C6H4
p-OMeC6H4
o-OMeC6H4
p-ClC6H4
ded good yields however, have limitations of long reaction time,
harsh reaction conditions and often expensive catalysts. Moreover,
the synthesis has been usually carried out in solvent leading to
complex isolation and recovery procedures. Consequently, there is
a scope of further improvement towards lower reaction time and
improved yields. The three-component condensation of aldehyde,
o-ClC6H4
2,4-Cl2C6H3
p-OHC6H4
m-OHC6H4
5-Br-2-OHC6H3
5-NO2-2-OHC6H3
2-OH–3-OMeC6H3
2-OH–3-OEtC6H3
p-MeC6H4
–CH]CH$C6H5
–CH(CH3)2
p-NO2C6H4
p-ClC6H4
b-naphthol and dimedone (5,5-dimethyl-1,3-cyclohexanedione)
5j
5k
5l
was performed in the presence of cerium(IV) ammonium nitrate
(CAN) in dichloromethane (DCM); however, the yield of 5 was low
along with long reaction time and various by-products. A by-
product, aryl-14H-dibenzo[a,j]xanthene was obtained as a major
product when phosphorous pentoxide (P2O5) was used as catalyst
in the refluxing DCM. Carrying out the condensation in refluxing
dichloromethane catalyzed by InCl3 resulted 5 in good yield with-
out side product but it requires long reaction time. Then, it was
decided to carry out the reactions under solvent free conditions
with above catalysts separately, and it was found that the reactions
proceeded smoothly in shorter reaction time giving higher yields.
In all cases InCl3 was found a better catalyst than P2O5 and provides
the desired products exclusively.
The reaction of 4-nitrobenzaldehyde (1.0 mmol), 2-naphthol
(1.0 mmol) and dimedone (1.2 mmol) in refluxing DCM was per-
formed as a model reaction in the presence of catalysts such as CAN
(50 mol %, 48 h), P2O5 (20 mol %, 24 h) and InCl3 (30 mol %, 20 h)
separately, resulting desired product in 50%, 22% and 78% yields,
respectively. When P2O5 was used as catalyst in DCM the reaction
profile was clean but the by-product aryl-14H-dibenzo[a,j]xan-
thene was obtained in maximum yield (70%). The above model
reaction was performed in the absence of solvent with the above
respective catalysts to give 45%, 80% and 88% yields. In the absence
of solvent the reaction completed within 30–40 min at 120 ꢀC. We
carried out another set of reaction under similar conditions taking
benzaldehyde, 2-naphthol and dimedone. The desired product was
obtained in 60%, 76% and 84% yields using catalysts CAN, P2O5 and
InCl3 respectively. The results show that under solvent free
5m
5n
5o
5p
5q
5r
6a
6b
6c
6d
6e
6f
C6H5
p-MeC6H4
2,4-Cl2C6H3
o-ClC6H4
o-NO2C6H4
4-BrC6H4
6g
6h
6i
4-FC6H4
a
For the experimental procedure see Section 4.2.
Yield of isolated and pure product.
b
Encouraged by the successful condensation of aldehydes, 2-
naphthol and dimedone under solvent-free condition to give
benzoxanthene derivatives, we next attempted the reaction with
1,3-dimethylbarbituric acid, aromatic aldehydes and 2-naphthol
under the optimized reaction conditions, which led to the exclusive
formation of diazabenzo[a]anthracene-9,11-diones (6) in good
yields. However, when some aliphatic aldehydes such as cinna-
maldehyde, isobutyraldehyde and cyclohexanaldehyde were used
in this protocol under the above optimized conditions, un-
fortunately, the expected products could not be obtained. The re-
sults are shown in Table 1.

G.C. Nandi et al. / Tetrahedron 65 (2009) 7129–7134
7131
A mechanistic rationale portraying the probable sequence of
events is given in Scheme 2. We supposed that the reaction may
proceed via the ortho-quinone methides intermediate, which was
formed by the nucleophilic addition of 2-naphthol to aldehyde
catalyzed by InCl3. Subsequent Michael addition of the o-QM with
cyclic 1,3-dicarbonyl and followed by addition of the phenolic hy-
droxy moiety to the carbonyl of ketone provides cyclic hemiketal
which on dehydration afforded 5. All the products 5 and 6 were
characterized by mp, IR and NMR spectra.
whole reaction mixture was heated in an oil bath at 120 ꢀC for the
stipulated period of time (Table 1) till the completion of the re-
action (monitored by TLC). Water (30 mL) was added to the reaction
mixture to remove unreacted reactants and the product was
extracted with ethyl acetate (3ꢁ20 mL). The organic layer was dried
over anhydrous MgSO4 and the solvent was evaporated under
vacuum. The residue obtained was purified by column chroma-
tography on silica gel to afford the pure product. Finally the prod-
ucts were recrystallized from methanol.
4.2.1. 9,9-Dimethyl-12-phenyl-8,9,10,12-tetrahydrobenzo[a]-
xanthen-11-one (5a)
InCl3
White solid; Rf¼0.50 (1:9 EtOAc/Hexane), mp 151–153 ꢀC. IR
InCl3
O
(KBr, cmꢂ1): 3055, 2954, 2884, 1651, 1374, 1229, 1178, 1076, 811. 1H
O
O
H
OH
H
3
R
R
R
H
NMR (300 MHz, CDCl3):
d
7.99 (d, J¼8.1 Hz, 1H), 7.78–7.74 (m, 2H),
1
O
OH
O
7.42–7.04 (m, 8H), 5.70 (s, 1H), 2.57 (s, 2H), 2.33 (d, J¼16.2 Hz, 1H),
InCl3
2.26 (d, J¼16.2 Hz, 1H), 1.11 (s, 3H), 0.96 (s, 3H). 13C NMR (75 MHz,
CDCl3):
d 196.8, 163.8, 147.7, 144.7, 131.4, 131.3, 128.7, 128.4, 128.3,
2
128.1, 126.9, 126.1, 124.8, 123.6, 117.6, 117.0, 114.2, 50.8, 41.3, 34.6,
32.2, 29.2, 27.1. MS (FAB): m/z¼355 [MþH]þ. Anal. Calcd for
C25H22O2: C, 84.72; H, 6.26. Found: C, 84.62; H, 6.50.
O
H
R
O
O
R
R
InCl3
O
OH
H
OH
4.2.2. 9,9-Dimethyl-12-(4-nitrophenyl)-8,9,10,12-tetrahydrobenzo-
[a]xanthen-11-one (5b)
H2O
O
O
5
White solid; Rf¼0.32 (1:9 EtOAc/Hexane), mp 178–180 ꢀC. IR
(KBr, cmꢂ1): 3077, 2934, 1645, 1597, 1516, 1377, 1343, 1225, 1177,
Scheme 2. Tentative mechanism for the formation of tetrahydrobenzo[a]xanthene-11-
ones (5).
1026, 827. 1H NMR (300 MHz, CDCl3):
d
8.04 (d, J¼8.4 Hz, 2H), 7.82–
7.79 (m, 3H), 7.52–7.33 (m, 5H), 5.81 (s, 1H), 2.59 (s, 2H), 2.36 (d,
J¼16.2 Hz, 1H), 2.26 (d, J¼16.2 Hz, 1H), 1.13 (s, 3H), 0.94 (s, 3H). 13C
3. Conclusion
NMR (75 MHz, CDCl3): d 196.6, 164.5, 151.8, 147.7, 146.2, 131.5, 130.9,
In conclusion, we have developed a solvent free, efficient and
environmentally benign methodology for the synthesis of 12-aryl/
alkyl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-ones and 8,10-di-
methyl-12-aryl-8,12-dihydro-7-oxa-8,10-diazabenzo[a]anthra-
cene-9,11-diones by a one-pot, multi-component reaction. The
advantages of this method over other existing methods are reduced
reaction times, higher yields, mild reaction condition, easy purifi-
cation and economic viability of the catalyst. We feel that this
economically viable procedure will find practical utility for the one-
pot synthesis of novel xanthenes and anthracenes. Further appli-
cations of InCl3 and P2O5 on the extension of this protocol are
ongoing in our group.
129.5, 129.3, 128.6, 127.3, 125.2, 123.5, 123.0, 117.0, 115.9, 112.9, 50.7,
41.3, 34.8, 32.2, 29.2, 27.0. MS (FAB): m/z¼400 [MþH]þ. Anal. Calcd
for C25H21NO4: C, 75.17; H, 5.30; N, 3.51. Found: C, 75.23; H, 5.32; N,
3.66.
4.2.3. 9,9-Dimethyl-12-(3-nitrophenyl)-8,9,10,12-tetrahydrobenzo-
[a]xanthen-11-one (5c)
White solid; Rf¼0.35 (1:9 EtOAc/Hexane), mp 168–170 ꢀC. IR
(KBr, cmꢂ1): 3071, 2955, 1649, 1528, 1372, 1356, 1224, 1172, 1025,
809. 1H NMR (300 MHz, CDCl3):
d 8.10 (s, 1H), 7.95–7.80 (m, 5H),
7.47–7.35 (m, 4H), 5.81 (s, 1H), 2.61 (s, 2H), 2.36 (d, J¼16.2 Hz, 1H),
2.26 (d, J¼16.2 Hz, 1H), 1.13 (s, 3H), 0.95 (s, 3H). 13C NMR (75 MHz,
CDCl3):
d 196.7, 164.5, 148.3, 147.7, 146.7, 134.7, 131.5, 130.9, 129.6,
4. Experimental
4.1. General
129.0, 128.6, 127.3, 125.1, 123.1, 123.0, 121.5, 117.1, 115.9, 113.1, 50.7,
41.3, 34.7, 32.2, 29.2, 27.1. MS (FAB): m/z¼400 [MþH]þ. Anal. Calcd
for C25H21NO4: C, 75.17; H, 5.30; N, 3.51. Found: C, 75.46; H, 5.42; N,
3.86.
All reagents were purchased from Merck, Aldrich, CDH and
Fluka and used without further purification. NMR spectra were
recorded on JEOL AL 300 FT NMR spectrometer. The IR spectra were
recorded on Varian 3100 FT-IR spectrophotometer. CHN analyses
were performed on Exeter Analytical Inc. ‘Model CE-400 CHN An-
alyzer’. All the reactions were monitored by TLC using precoated
sheets of silica gel G/UV-254 of 0.25 mm thickness (Merck 60F254).
Melting points were determined with BUCHI B-540 melting point
apparatus and are uncorrected.
4.2.4. 9,9-Dimethyl-12-(2-nitrophenyl)-8,9,10,12-tetrahydrobenzo-
[a]xanthen-11-one (5d)
Pale yellow solid; Rf¼0.30 (1:9 EtOAc/Hexane), mp 223–225 ꢀC.
IR (KBr, cmꢂ1): 3069, 2957, 2926, 1651, 1526, 1369, 1227, 1170, 1028,
823. 1H NMR (300 MHz, CDCl3):
d
8.56 (d, J¼8.1 Hz, 1H), 7.86–7.77
(m, 3H), 7.46–7.03 (m, 6H), 6.58 (s, 1H), 2.60 (d, J¼17.4 Hz, 1H), 2.52
(d, J¼17.4 Hz, 1H), 2.29 (d, J¼16.2 Hz, 1H), 2.19 (d, J¼16.2 Hz, 1H),
1.11 (s, 3H), 0.86 (s, 3H). 13C NMR (75 MHz, CDCl3):
d 196.9, 164.5,
148.6, 142.1, 132.9, 131.6, 131.5, 131.0, 129.9, 129.0, 128.3, 127.6, 127.2,
126.5, 124.3, 123.7, 117.5, 117.0, 113.2, 50.4, 41.3, 34.8, 32.3, 29.3, 27.1.
MS (FAB): m/z¼400 [MþH]þ. Anal. Calcd for C25H21NO4: C, 75.17; H,
5.30; N, 3.51. Found: C, 75.42; H, 5.59; N, 3.56.
4.2. General procedure for synthesis of 12-aryl/alkyl-8,9,10,12-
tetrahydrobenzo[a]xanthene-11-one (5) and 8,10-dimethyl-
12-aryl-8,12-dihydro-7-oxa-8,10-diazabenzo[a]anthracene-
9,11-dione (6)
4.2.5. 12-(4-Methoxyphenyl)-9,9-dimethyl-8,9,10,12-
tetrahydrobenzo[a]xanthen-11-one (5e)
The aldehyde (1.0 mmol), cyclic-1,3-dicarbonyl compound
(1.2 mmol) and 2-naphthol (1.0 mmol) were grinded in a mortar.
The catalyst InCl3 (30 mol %) or P2O5 (20 mol %) was added to the
reaction mixture and grinded further for additional 15 min. The
White solid; Rf¼0.50 (1:9 EtOAc/Hexane), mp 204–205 ꢀC. IR
(KBr, cmꢂ1): 3057, 2949, 1643, 1227, 1172, 1024. 1H NMR (300 MHz,
CDCl3):
d
7.99 (d, J¼8.1 Hz, 1H), 7.77–7.72 (m, 2H), 7.44–7.22 (m,

7132
G.C. Nandi et al. / Tetrahedron 65 (2009) 7129–7134
5H), 6.70 (d, J¼8.4 Hz, 2H), 5.65 (s, 1H), 3.68 (s, 3H), 2.55 (s, 2H),
2.33 (d, J¼16.2 Hz, 1H), 2.26 (d, J¼16.2 Hz, 1H), 1.11 (s, 3H), 0.97 (s,
131.4, 131.3, 129.4, 128.6, 128.3, 126.9, 124.8, 123.7, 117.8, 116.9, 115.3,
114.4, 50.7, 41.3, 33.8, 32.2, 29.1, 27.0. MS (FAB): m/z¼371 [MþH]þ.
Anal. Calcd for C25H22O3: C, 81.06; H, 5.99. Found: C, 81.26; H, 6.12.
3H). 13C NMR (75 MHz, CDCl3):
d 196.6, 163.1, 156.7, 146.5, 136.0,
133.6, 130.4, 130.2, 128.3, 127.3, 126.6, 125.2, 123.8, 122.2, 117.0,
116.8, 115.9, 113.3, 112.5, 53.9, 49.7, 40.3, 32.7, 31.2, 28.2, 26.0. MS
(FAB): m/z¼385 [MþH]þ. Anal. Calcd for C26H24O3: C, 81.22; H, 6.29.
Found: C, 81.41; H, 6.07.
4.2.11. 12-(3-Hydroxyphenyl)-9,9-dimethyl-8,9,10,12-
tetrahydrobenzo[a]xanthen-11-one (5k)
White solid; Rf¼0.35 (1:4 EtOAc/Hexane), mp 240–241 ꢀC. IR
(KBr, cmꢂ1): 3409, 3054, 2951, 1640, 1589, 1371, 1222, 1170, 1023. 1H
4.2.6. 12-(2-Methoxyphenyl)-9,9-dimethyl-8,9,10,12-
tetrahydrobenzo[a]xanthen-11-one (5f)
NMR (300 MHz, CDCl3):
d
7.99 (d, J¼8.1 Hz, 1H), 7.79–7.74 (m, 2H),
7.45–7.30 (m, 3H), 7.04 (t, J¼7.8 Hz, 1H), 6.93 (s, 1H), 6.83 (d,
J¼7.5 Hz,1H), 6.56 (d, J¼6.0 Hz,1H), 5.69 (s,1H), 5.43 (s,1H), 2.56 (s,
2H), 2.36 (d, J¼16.2 Hz, 1H), 2.30 (d, J¼16.2 Hz, 1H), 1.11 (s, 3H), 0.98
White solid; Rf¼0.48 (1:9 EtOAc/Hexane), mp 163–165 ꢀC. IR
(KBr, cmꢂ1): 3072, 2930, 1649, 1376, 1231, 1170, 1029. 1H NMR
(300 MHz, CDCl3):
d
8.29 (d, J¼8.4 Hz, 1H), 7.74–7.67 (m, 2H), 7.45–
(s, 3H). 13C NMR (75 MHz, CDCl3):
d 198.3, 164.5, 148.4, 147.6, 146.3,
7.25 (m, 4H), 7.05 (t, J¼7.2 Hz, 1H), 6.81–6.74 (m, 2H), 5.95 (s, 1H),
134.5, 131.5, 130.9, 129.6, 129.1, 128.7, 127.5, 125.1, 123.4, 123.0, 121.7,
117.3, 115.7, 113.6, 50.7, 41.3, 34.7, 32.2, 29.2, 27.0. MS (FAB):
m/z¼371 [MþH]þ. Anal. Calcd for C25H22O3: C, 81.06; H, 5.99.
Found: C, 81.20; H, 6.06.
3.94 (s, 3H), 2.58 (s, 2H), 2.32 (d, J¼16.2 Hz, 1H), 2.22 (d, J¼16.2 Hz,
1H), 1.12 (s, 3H), 1.00 (s, 3H). 13C NMR (75 MHz, CDCl3):
d 196.8,
164.2,156.3, 147.6, 133.2,131.8, 131.2, 130.5, 128.3, 128.1, 127.5, 126.7,
124.6, 123.9, 120.6, 118.2, 116.9, 113.6, 111.4, 55.8, 50.8, 41.4, 32.9,
32.2, 29.4, 27.0. MS (FAB): m/z¼385 [MþH]þ. Anal. Calcd for
C26H24O3: C, 81.22; H, 6.29. Found: C, 81.42; H, 6.31.
4.2.12. 12-(5-Bromo-2-hydroxyphenyl)-9,9-dimethyl-8,9,10,12-
tetrahydrobenzo[a]xanthen-11-one (5l)
White solid; Rf¼0.45 (1:4 EtOAc/Hexane), mp 266–268 ꢀC. IR
4.2.7. 12-(4-Chlorophenyl)-9,9-dimethyl-8,9,10,12-
(KBr, cmꢂ1): 3116, 2957, 2927, 1624, 1590, 1382, 1225, 1143, 1030. 1H
tetrahydrobenzo[a]xanthen-11-one (5g)
NMR (300 MHz, CDCl3): d 7.83–7.80 (m, 2H), 7.60–7.26 (m, 4H), 7.10
White solid; Rf¼0.50 (1:9 EtOAc/Hexane), mp 180–182 ꢀC. IR
(d, J¼6.0 Hz,1H), 6.91 (d, J¼8.4 Hz,1H), 6.65 (s,1H), 5.71 (s,1H), 4.73
(s, 1H), 2.70 (d, J¼17.7 Hz, 1H), 2.61 (d, J¼17.7 Hz, 1H), 2.45 (d,
J¼17.1 Hz, 1H), 2.36 (d, J¼17.1 Hz, 1H), 1.15 (s, 3H), 1.02 (s, 3H). 13C
(KBr, cmꢂ1): 3072, 2925, 1645, 1374, 1226, 1174, 1088. 1H NMR
(300 MHz, CDCl3):
d
7.90 (d, J¼8.1 Hz, 1H), 7.79–7.75 (m, 2H), 7.45–
7.11 (m, 7H), 5.67 (s, 1H), 2.56 (s, 2H), 2.34 (d, J¼16.2 Hz, 1H), 2.26
NMR (75 MHz, CDCl3): d 200.7, 167.3, 152.1, 147.7, 134.9, 134.8, 131.6,
(d, J¼16.2 Hz, 1H), 1.12 (s, 3H), 0.96 (s, 3H). 13C NMR (75 MHz,
131.2,130.8,129.5,128.3,127.6,125.4,123.1,120.9,120.8,116.6,113.6,
113.3, 50.1, 41.5, 32.4, 29.6, 28.8, 27.3. MS (FAB): m/z¼449 [MþH]þ.
Anal. Calcd for C25H21BrO3: C, 66.82; H, 4.71. Found: C, 67.01; H, 4.95.
CDCl3):
d 196.6, 164.5, 151.6, 147.4, 146.3, 131.7, 130.5, 129.5, 129.2,
128.6, 127.3, 125.1, 123.4, 123.0, 116.9, 115.9, 112.9, 50.7, 41.3, 34.8,
32.2, 29.2, 27.0. MS (FAB): m/z¼389 [MþH]þ. Anal. Calcd for
C25H21ClO2: C, 77.21; H, 5.44. Found: C, 77.32; H, 5.53.
4.2.13. 12-(5-Nitro-2-hydroxyphenyl)-9,9-dimethyl-8,9,10,12-
tetrahydrobenzo[a]xanthen-11-one (5m)
4.2.8. 12-(2-Chlorophenyl)-9,9-dimethyl-8,9,10,12-
White solid; Rf¼0.50 (1:4 EtOAc/Hexane), mp 263–265 ꢀC. IR
tetrahydrobenzo[a]xanthen-11-one (5h)
(KBr, cmꢂ1): 3316, 2940, 1631, 1492, 1373, 1334, 1231, 1026, 830. 1H
White solid; Rf¼0.45 (1:9 EtOAc/Hexane), mp 179–180 ꢀC. IR
NMR (300 MHz, CDCl3): d 10.43 (s, 1H), 7.93–7.79 (m, 3H), 7.49–7.37
(KBr, cmꢂ1): 3075, 2930, 1648, 1372, 1229, 1179, 1030, 748. 1H NMR
(m, 5H), 7.09 (d, J¼9.0 Hz, 1H), 5.75 (s, 1H), 2.73 (d, J¼17.7 Hz, 1H),
(300 MHz, CDCl3):
d
8.23 (d, J¼8.4 Hz, 1H), 7.76–7.72 (m, 2H), 7.49–
2.65 (d, J¼17.7 Hz, 1H), 2.49 (d, J¼17.1 Hz, 1H), 2.41 (d, J¼17.1 Hz,
7.26 (m, 5H), 7.07–6.96 (m, 2H), 5.98 (s, 1H), 2.60 (s, 2H), 2.34 (d,
1H), 1.17 (s, 3H), 1.01 (s, 3H). 13C NMR (75 MHz, CDCl3):
d 201.1,
J¼16.2 Hz, 1H), 2.24 (d, J¼16.2 Hz, 1H), 1.13 (s, 3H), 0.99 (s, 3H). 13C
168.2, 159.4, 147.9, 142.0, 133.1,131.7, 130.5, 130.0, 128.6, 127.7, 125.5,
125.1, 124.2, 122.6, 119.2, 116.8, 115.7, 112.7, 50.0, 41.5, 32.3, 29.0,
28.2, 27.1. MS (FAB): m/z¼416 [MþH]þ. Anal. Calcd for C25H21NO5:
C, 72.28; H, 5.10; N, 3.37. Found: C, 72.36; H, 5.21; N, 3.57.
NMR (75 MHz, CDCl3): d 196.6, 164.1, 147.6, 142.1, 132.9, 131.6, 131.5,
131.3, 129.9, 129.0, 128.3, 127.6,127.0, 126.8, 124.9, 123.9, 117.3, 117.0,
113.4, 50.8, 41.4, 32.9, 32.1, 29.3, 27.0. MS (FAB): m/z¼389 [MþH]þ.
Anal. Calcd for C25H21ClO2: C, 77.21; H, 5.44. Found: C, 77.49; H, 5.56.
4.2.14. 12-(2-Hydroxy-3-methoxyphenyl)-9,9-dimethyl-8,9,10,12-
tetrahydrobenzo[a]xanthen-11-one (5n)
4.2.9. 12-(2,4-Dichlorophenyl)-9,9-dimethyl-8,9,10,12-
tetrahydrobenzo[a]xanthen-11-one (5i)
White solid; Rf¼0.40 (1:4 EtOAc/Hexane), mp 213–215 ꢀC. IR
White solid; Rf¼0.50 (1:9 EtOAc/Hexane), mp 178–180 ꢀC. IR
(KBr, cmꢂ1): 3283, 3077, 2951, 1622, 1377, 1237, 1069. 1H NMR
(KBr, cmꢂ1): 3058, 2952, 2869, 1652, 1369, 1227, 1103, 1024, 751. 1H
(300 MHz, CDCl3):
d 8.66 (s, 1H), 7.83–7.73 (m, 3H), 7.40–7.25 (m,
NMR (300 MHz, CDCl3):
d
8.13 (d, J¼8.4 Hz, 1H), 7.78–7.74 (m, 2H),
3H), 6.59–6.57 (m, 2H), 6.32 (d, J¼4.5 Hz, 1H), 5.82 (s, 1H), 3.85 (s,
7.48–7.36 (m, 2H), 7.29–7.19 (m, 3H), 7.04 (d, J¼6.9 Hz, 1H), 5.93 (s,
3H), 2.59 (s, 2H), 2.42 (d, J¼16.2 Hz, 1H), 2.34 (d, J¼16.2 Hz, 1H), 1.13
1H), 2.60 (s, 2H), 2.35 (d, J¼16.2 Hz, 1H), 2.25 (d, J¼16.2 Hz, 1H), 1.14
(s, 3H), 0.99 (s, 3H). 13C NMR (75 MHz, CDCl3):
d 199.8, 166.3, 149.1,
(s, 3H), 1.00 (s, 3H). 13C NMR (75 MHz, CDCl3):
d
196.7, 164.4, 147.6,
147.6, 142.2, 132.7, 131.3, 131.2, 128.9, 128.1, 127.3, 125.1, 123.5, 120.7,
120.6, 117.5, 116.5, 113.7, 109.4, 55.7, 50.2, 41.5, 32.3, 29.0, 28.1, 27.1.
MS (FAB): m/z¼401 [MþH]þ. Anal. Calcd for C26H24O4: C, 77.98; H,
6.04. Found: C, 78.10; H, 6.33.
140.7, 133.6, 132.5, 132.4, 131.4, 131.3, 129.6, 129.3, 128.4, 127.3,
127.2, 125.0, 123.6, 117.0, 116.7, 112.9, 50.8, 41.4, 32.6, 32.1, 29.3, 27.0.
MS (FAB): m/z¼423 [MþH]þ. Anal. Calcd for C25H20Cl2O2: C, 70.93;
H, 4.76. Found: C, 70.72; H, 4.85.
4.2.15. 12-(2-Hydroxy-3-ethoxyphenyl)-9,9-dimethyl-8,9,10,12-
tetrahydrobenzo[a]xanthen-11-one (5o)
4.2.10. 12-(4-Hydroxyphenyl)-9,9-dimethyl-8,9,10,12-
tetrahydrobenzo[a]xanthen-11-one (5j)
White solid; Rf¼0.40 (1:4 EtOAc/Hexane), mp 190–192 ꢀC. IR
White solid; Rf¼0.30 (1:4 EtOAc/Hexane), mp 223–225 ꢀC. IR
(KBr, cmꢂ1): 3215, 3059, 2962, 2927, 1629, 1386, 1226, 1121, 1057. 1H
(KBr, cmꢂ1): 3305, 2957, 1638, 1572, 1378, 1225, 1176, 1024. 1H NMR
NMR (300 MHz, CDCl3):
d
8.32 (s, 1H), 7.91 (d, J¼8.1 Hz, 1H), 7.75–
(300 MHz, CDCl3):
d
7.98 (d, J¼8.1 Hz, 1H), 7.78–7.73 (m, 2H), 7.45–
7.73 (m, 2H), 7.44–7.25 (m, 3H), 6.60–6.52 (m, 2H), 6.38 (dd, J¼1.8,
6.9 Hz, 1H), 5.83 (s, 1H), 4.07 (q, J¼6.9 Hz, 2H), 2.59 (s, 2H), 2.41 (d,
J¼16.2 Hz, 1H), 2.33 (d, J¼16.2 Hz, 1H), 1.49 (t, J¼6.9 Hz, 3H), 1.13 (s,
7.15 (m, 5H), 6.61 (d, J¼8.4 Hz, 2H), 5.63 (s, 1H), 5.49 (s, 1H), 2.56 (s,
2H), 2.34 (d, J¼16.2 Hz, 1H), 2.27 (d, J¼16.2 Hz, 1H), 1.12 (s, 3H), 0.97
(s, 3H). 13C NMR (75 MHz, CDCl3):
d
198.2, 164.5, 154.5, 147.4, 136.3,
3H), 0.99 (s, 3H). 13C NMR (75 MHz, CDCl3):
d 199.2, 165.9, 148.0,

G.C. Nandi et al. / Tetrahedron 65 (2009) 7129–7134
7133
147.5, 142.4, 132.4, 131.3, 131.2, 128.7, 128.0, 127.2, 124.9, 123.5,
4.2.21. 8,10-Dimethyl-12-phenyl-8,12-dihydro-7-oxa-8,10-
120.8, 120.4, 117.5, 116.5, 113.6, 110.5, 64.1, 50.2, 41.3, 32.1, 29.0, 28.2,
27.0, 14.8. MS (FAB): m/z¼415 [MþH]þ. Anal. Calcd for C27H26O4: C,
78.24; H, 6.32. Found: C, 78.52; H, 6.60.
diazabenzo[a]anthracene-9,11-dione (6c)
White solid; Rf¼0.35 (1:4 EtOAc/Hexane), mp 226–228 ꢀC. IR
(KBr, cmꢂ1): 2928, 1706, 1651, 1485, 1233, 1179. 1H NMR (300 MHz,
CDCl3):
7.23–7.10 (m, 3H), 5.81 (s, 1H), 3.61 (s, 3H), 3.33 (s, 3H). 13C NMR
(75 MHz, CDCl3): 161.9, 152.2, 150.6, 147.1, 143.8, 131.7, 130.9,
129.4, 128.5, 128.4, 128.2, 127.4, 126.7, 125.4, 123.9, 117.4, 116.2, 91.4,
35.9, 29.0, 28.1. MS (FAB): m/z¼371 [MþH]þ. Anal. Calcd for
C23H18N2O3: C, 74.58; H, 4.90; N, 7.56. Found: C, 74.92; H, 5.12; N,
7.89.
d
7.96 (d, J¼7.8 Hz, 1H), 7.85 (m, 2H), 7.46–7.35 (m, 5H),
4.2.16. 9,9-Dimethyl-12-p-tolyl-8,9,10,12-tetrahydro-
benzo[a]xanthen-11-one (5p)
d
White solid; Rf¼0.50 (1:9 EtOAc/Hexane), mp 176–178 ꢀC. IR
(KBr, cmꢂ1): 3071, 2949, 2865, 1648, 1510, 1372, 1230, 1071, 814. 1H
NMR (300 MHz, DMSO-d6): d 8.04–7.88 (m, 3H), 7.46–7.42 (m, 3H),
7.17–7.15 (m, 2H), 6.98 (d, J¼7.2 Hz, 2H), 5.52 (s, 1H), 2.72 (d,
J¼17.4 Hz,1H), 2.60 (d, J¼17.4 Hz,1H), 2.41 (d, J¼16.2 Hz,1H), 2.30 (d,
J¼16.2 Hz, 1H), 2.14 (s, 3H), 1.06 (s, 3H), 0.89 (s, 3H). 13C NMR
4.2.22. 8,10-Dimethyl-12-p-tolyl-8,12-dihydro-7-oxa-8,10-
diazabenzo[a]anthracene-9,11-dione (6d)
(75 MHz, CDCl3): d 196.3,163.0,153.1,146.5,140.7,134.6,133.6,130.3,
128.5, 127.9, 127.2, 126.6, 125.9, 123.8, 122.6, 117.1, 116.8, 115.9, 113.3,
49.7, 40.3, 33.2, 31.2, 28.2, 26.1, 19.9. MS (FAB): m/z¼369 [MþH]þ.
Anal. Calcd for C26H24O2: C, 84.75; H, 6.57. Found: C, 84.52; H, 6.38.
White solid; Rf¼0.37 (1:4 EtOAc/Hexane), mp 196–198 ꢀC. IR
(KBr, cmꢂ1): 2924, 1700, 1643, 1487, 1232, 1179. 1H NMR (300 MHz,
CDCl3):
3H), 7.26 (d, J¼7.5 Hz, 2H), 7.02 (d, J¼7.5 Hz, 2H), 5.78 (s, 1H), 3.60
(s, 3H), 3.32 (s, 3H), 2.21 (s, 3H). 13C NMR (75 MHz, CDCl3):
161.9,
d
7.98 (d, J¼8.4 Hz, 1H), 7.84–7.80 (m, 2H), 7.46–7.37 (m,
4.2.17. 9,9-Dimethyl-12-styryl-8,9,10,12-tetrahydrobenzo[a]-
xanthen-11-one (5q)
d
152.1, 150.6, 147.1, 140.9, 136.3, 131.7, 130.9, 129.3, 129.1, 128.4, 128.0,
127.3, 125.4, 123.9, 117.5, 116.2, 91.5, 35.5, 28.9, 28.1, 20.9. MS (FAB):
m/z¼385 [MþH]þ. Anal. Calcd for C24H20N2O3: C, 74.98; H, 5.24; N,
7.29. Found: C, 74.88; H, 5.19; N, 7.20.
White solid; Rf¼0.35 (1:9 EtOAc/Hexane), mp 148–150 ꢀC. IR
(KBr, cmꢂ1): 3080, 2927, 1648, 1464, 1383, 2225, 908. 1H NMR
(300 MHz, CDCl3):
d
8.06 (d, J¼8.4 Hz, 1H), 7.83–7.75 (m, 2H), 7.53–
7.17 (m, 8H), 6.45 (dd, J¼6.3 Hz, 1H), 6.17 (d, J¼15.9 Hz, 1H), 5.33 (d,
J¼6.3 Hz, 1H), 2.56 (s, 2H), 2.37 (s, 2H), 1.15 (s, 6H). 13C NMR
4.2.23. 12-(2,4-Dichlorophenyl)-8,10-dimethyl-8,12-dihydro-7-
oxa-8,10-diazabenzo[a]anthracene-9,11-dione (6e)
(75 MHz, CDCl3): d 197.1,165.0, 147.8, 137.0,131.2,130.8, 130.6, 128.7,
128.3, 128.2, 127.1, 127.0, 126.2, 124.9, 123.7, 117.0, 112.1, 50.9, 41.4,
32.3, 31.2, 29.2, 27.5. MS (FAB): m/z¼381 [MþH]þ. Anal. Calcd for
C27H24O2: C, 85.23; H, 6.36. Found: C, 85.45; H, 6.30.
White solid; Rf¼0.35 (1:4 EtOAc/Hexane), mp 222–224 ꢀC. IR
(KBr, cmꢂ1): 3060, 2950, 1709, 1658, 1479, 1232, 1181. 1H NMR
(300 MHz, CDCl3):
7.44 (m, 2H), 7.37–7.31 (m, 3H), 7.08 (d, J¼7.8 Hz, 1H), 6.07 (s, 1H),
3.64 (s, 3H), 3.32 (s, 3H). 13C NMR (75 MHz, CDCl3):
161.6, 152.4,
d
8.11 (d, J¼8.1 Hz, 1H), 7.84–7.82 (m, 2H), 7.52–
4.2.18. 12-Isopropyl-9,9-dimethyl-8,9,10,12-tetrahydrobenzo[a]-
xanthen-11-one (5r)
d
150.5, 146.9, 139.7, 133.7, 133.0, 132.3, 131.6, 130.9, 129.9, 129.7,
128.6,127.6,127.4,125.5,123.7,116.2, 89.9, 33.8, 29.1, 28.1. MS (FAB):
m/z¼439 [MþH]þ. Anal. Calcd for C23H16Cl2N2O3: C, 62.88; H, 3.67;
N, 6.38. Found: C, 62.82; H, 3.59, N, 6.30.
White solid; Rf¼0.40 (1:9 EtOAc/Hexane), mp 116–117 ꢀC. IR
(KBr, cmꢂ1): 3066, 2956, 1646, 1384, 1218, 1172, 817, 544. 1H NMR
(300 MHz, CDCl3):
d
8.11 (d, J¼8.4 Hz, 1H), 7.82 (d, J¼8.1 Hz, 1H),
7.71 (d, J¼8.7 Hz, 1H), 7.55 (t, J¼7.5 Hz, 1H), 7.44 (t, J¼7.5 Hz, 1H),
7.23 (d, J¼9.0 Hz, 1H), 4.71 (d, J¼3.0 Hz, 1H), 2.64 (d, J¼18.0 Hz, 1H),
2.54 (d, J¼18.0 Hz, 1H), 2.44 (d, J¼16.5 Hz, 1H), 2.33 (d, J¼16.5 Hz,
1H), 2.11 (m,1H),1.23 (s, 3H),1.14 (s, 3H), 0.91 (d, J¼6.9 Hz, 3H), 0.68
4.2.24. 12-(2-Chlorophenyl)-8,10-dimethyl-8,12-dihydro-7-oxa-
8,10-diazabenzo[a]anthracene-9,11-dione (6f)
White solid; Rf¼0.32 (1:4 EtOAc/Hexane), mp 270–272 ꢀC. IR
(d, J¼6.9 Hz, 3H). 13C NMR (75 MHz, CDCl3):
d 197.4, 167.0, 149.0,
(KBr, cmꢂ1): 3058, 2951, 1705, 1655, 1456, 1271, 1183. 1H NMR
131.4, 128.4, 127.8, 126.5, 124.5, 123.4, 118.8, 116.7, 111.5, 102.5, 50.9,
41.4, 35.3, 32.8, 31.7, 29.9, 27.1, 20.8, 18.2. MS (FAB): m/z¼321
[MþH]þ. Anal. Calcd for C22H24O2: C, 82.46; H, 7.55. Found: C,
82.78; H, 7.86.
(300 MHz, CDCl3):
7.29 (m, 5H), 7.09–7.04 (m, 2H), 6.12 (s,1H), 3.64 (s, 3H), 3.31 (s, 3H).
13C NMR (75 MHz, CDCl3):
161.6, 152.4, 150.6, 146.9, 141.1, 133.0,
d
8.20 (d, J¼8.4 Hz, 1H), 7.83–7.78 (m, 2H), 7.53–
d
131.6, 131.5, 131.1, 130.0, 129.7, 128.4, 128.0, 127.5, 127.0, 125.0, 124.0,
116.9, 116.2, 90.4, 34.1, 29.0, 28.1. MS (FAB): m/z¼405 [MþH]þ. Anal.
Calcd for C23H17ClN2O3: C, 68.23; H, 4.23; N, 6.92. Found: C, 68.10;
H, 4.15; N, 6.85.
4.2.19. 8,10-Dimethyl-12-(4-nitrophenyl)-8,12-dihydro-7-oxa-8,10-
diazabenzo[a]anthracene-9,11-dione (6a)
White solid; Rf¼0.35 (1:4 EtOAc/Hexane), mp 288–290 ꢀC. IR
(KBr, cmꢂ1): 3070, 2924, 2855, 1709, 1667, 1596, 1227, 1175. 1H NMR
4.2.25. 8,10-Dimethyl-12-(2-nitrophenyl)-8,12-dihydro-7-oxa-
8,10-diazabenzo[a]anthracene-9,11-dione (6g)
(300 MHz, CDCl3):
7.42 (m, 5H), 5.90 (s, 1H), 3.63 (s, 3H), 3.33 (s, 3H). 13C NMR
(75 MHz, CDCl3): 161.7, 152.4, 150.7, 150.4, 147.1, 146.5, 131.7, 130.4,
d
8.07 (d, J¼8.4 Hz, 2H), 7.91–7.79 (m, 3H), 7.56–
White solid; Rf¼0.25 (1:4 EtOAc/Hexane), mp 288–290 ꢀC. IR
d
(KBr, cmꢂ1): 3062, 2954, 1708, 1651, 1484, 1233, 1177. 1H NMR
130.2, 129.2, 128.7, 127.8, 125.7, 123.7, 123.3, 116.3, 115.7, 89.9, 36.0,
29.1, 28.2. MS (FAB): m/z¼416 [MþH]þ. Anal. Calcd for C23H17N3O5:
C, 66.50; H, 4.12; N, 10.12. Found: C, 66.82; H, 4.40; N, 10.38.
(300 MHz, CDCl3):
7.38 (m, 3H), 7.29–7.23 (m, 2H), 7.04 (d, J¼7.5 Hz, 1H), 6.76 (s, 1H),
3.58 (s, 3H), 3.26 (s, 3H). 13C NMR (75 MHz, CDCl3):
161.5, 151.6,
d
8.48 (d, J¼7.8 Hz, 1H), 7.90–7.81 (m, 3H), 7.49–
d
150.4, 149.1, 147.4, 138.2, 132.9, 131.7, 131.2, 130.9, 130.3, 128.3, 127.8,
127.4,125.7,124.6,124.5,116.2,115.7, 90.3, 30.9, 29.0, 28.1. MS (FAB):
m/z¼416 [MþH]þ. Anal. Calcd for C23H17N3O5: C, 66.50; H, 4.12; N,
10.12. Found: C, 66.72; H, 4.09; N, 10.01.
4.2.20. 8,10-Dimethyl-12-(4-chlorophenyl)-8,12-dihydro-7-oxa-
8,10-diazabenzo[a]anthracene-9,11-dione (6b)
White solid; Rf¼0.40 (1:4 EtOAc/Hexane), mp 270–272 ꢀC. IR
(KBr, cmꢂ1): 2924, 2855, 1708, 1671, 1648, 1225, 1174, 1081. 1H NMR
(300 MHz, CDCl3):
d
7.88–7.81 (m, 3H), 7.47–7.14 (m, 7H), 5.78 (s,
161.9,
4.2.26. 12-(4-Bromophenyl)-8,10-dimethyl-8,12-dihydro-7-oxa-
8,10-diazabenzo[a]anthracene-9,11-dione (6h)
1H), 3.60 (s, 3H), 3.33 (s, 3H). 13C NMR (75 MHz, CDCl3):
d
152.2, 150.5, 147.1, 142.3, 132.5, 131.7, 130.7, 129.7, 129.6, 128.5, 127.6,
125.6, 123.7, 116.7, 116.3, 90.9, 35.4, 29.1, 28.2. MS (FAB): m/z¼405
[MþH]þ. Anal. Calcd for C23H17ClN2O3: C, 68.23; H, 4.23; N, 6.92.
Found: C, 68.54; H, 4.63; N, 7.12.
White solid; Rf¼0.40 (1:4 EtOAc/Hexane), mp 243–245 ꢀC. IR
(KBr, cmꢂ1): 2929, 1705, 1646, 1484, 1234. 1H NMR (300 MHz,
CDCl3):
d
7.88 (m, 3H), 7.48–7.23 (m, 7H), 5.77 (s, 1H), 3.61 (s, 3H),
161.8, 152.2, 150.5, 147.1,
3.33 (s, 3H). 13C NMR (75 MHz, CDCl3):
d

7134
G.C. Nandi et al. / Tetrahedron 65 (2009) 7129–7134
Rodriguez, J. Eur. J. Org. Chem. 2004, 4957; (d) Groenendaal, B.; Ruijter, E.;
Orru, R. V. A. Chem. Commun. 2008, 5474; (e) Wessjohann, L. A.; Rivera, D.
G.; Vercillo, O. E. Chem. Rev. 2009, 109, 796; (f) Ramo´n, D. J.; Yus, M. Angew.
Chem., Int. Ed. 2005, 44, 1602.
5. Hantzsch, A. Liebigs Ann. Chem. 1882, 215, 1.
6. Biginelli, P. Gazz. Chim. Ital 1893, 23, 360.
142.8, 131.7, 131.5, 130.6, 129.9, 129.7, 128.5, 127.5, 125.5, 123.6,
120.5, 116.6, 116.2, 90.8, 35.5, 29.0, 28.1. MS (FAB): m/z¼449
[MþH]þ. Anal. Calcd for C23H17BrN2O3: C, 61.48; H, 3.81; N, 6.23.
Found: C, 61.40; H, 3.75; N, 6.10.
7. (a) Scho¨pf, C. Angew. Chem. 1937, 50, 779; (b) Scho¨pf, C. Angew. Chem. 1937,
50, 797.
4.2.27. 12-(4-Fluorophenyl)-8,10-dimethyl-8,12-dihydro-7-oxa-
8,10-diazabenzo[a]anthracene-9,11-dione (6i)
8. (a) Tietze, L. F. J. Heterocycl. Chem. 1990, 27, 47; (b) Ramachary, D. B.; Chowdari,
N. S.; Barbas, C. F., III. Angew. Chem., Int. Ed. 2003, 42, 4233.
9. (a) Komnenos, T. Justus Liebigs Ann. Chem. 1883, 218, 145; (b) Betancort, J. M.;
Sakthivel, K.; Thayumanava, R.; Barbas, C. F., III. Tetrahedron Lett. 2001, 42,
4441.
10. Lambert, R. W.; Martin, J. A.; Merrett, J. H.; Parkes, K. E. B.; Thomas, G. J. PCT Int.
Appl. WO 9,706,178, 1997.
11. Poupelin, J. P.; Saint-Ruf, G.; Foussard-Blanpin, O.; Narcisse, G.; Uchida-Ernouf,
G.; Lacroix, R. Eur. J. Med. Chem. 1978, 13, 67.
White solid; Rf¼0.30 (1:4 EtOAc/Hexane), mp 303–305 ꢀC. IR
(KBr, cmꢂ1): 2925, 1706, 1670, 1597, 1452, 1165. 1H NMR (300 MHz,
CDCl3):
2H), 5.79 (s, 1H), 3.61 (s, 3H), 3.34 (s, 3H). 13C NMR (75 MHz, CDCl3):
161.6, 152.4, 150.4, 147.0, 142.5, 131.4, 131.0, 130.2, 129.8, 129.2,
d
7.90–7.81 (m, 3H), 7.47–7.30 (m, 5H), 6.90 (t, J¼8.7 Hz,
d
128.5, 127.5, 125.6, 123.5, 120.3, 116.3, 116.0, 90.5, 35.3, 29.0, 28.2.
MS (FAB): m/z¼389 [MþH]þ. Anal. Calcd for C23H17FN2O3: C, 71.13;
H, 4.41; N, 7.21. Found: C, 71.10; H, 4.30; N, 7.13.
12. Hideo, T.; Teruomi, J. Jpn. Patent 56,005,480, 1981.
13. (a) Buu-Hoi, N. P.; Saint-Ruf, G.; De, A.; Hieu, H. T. Bull. Chim. Ther. 1972, 7, 83;
(b) Saint-Ruf, G.; Hieu, H. T.; Poupelin, J. P. Naturwissenschaften 1975, 62, 584.
14. (a) Ion, R.-M. Prog. Catal. 1997, 6, 55; (b) Ion, R. M.; Planner, A.; Wiktorowicz, K.;
Frackowiak, D. Acta Biochim. Pol. 1998, 45, 833.
15. (a) Banerjee, A.; Mukherjee, A. K. Stain Technol. 1981, 56, 83; (b) Menchen, S. M.;
Benson, S. C.; Lam, J. Y. L.; Zhen, W. -G.; Sun, D. -Q.; Rosenblum, B. B.; Khan, S.
H.;Taing, M. U.S. Patent 6,583,168, 2003.
16. (a) Sirkencioglu, O.; Talinli, N.; Akar, A. J. Chem. Res. 1995, 502; (b) Ahmad, M.;
King, T. A.; Ko, D.-K.; Cha, B. H.; Lee, J. J. Phys. D: Appl. Phys. 2002, 35, 1473.
17. Knight, C. G.; Stephens, T. Biochem. J. 1989, 258, 683.
18. For reviews see: (a) Li, C.-J.; Chan, T.-H. Tetrahedron 1999, 55, 11149; (b) Sharma,
S. D.; Hazarika, P.; Konwar, D. Tetrahedron Lett. 2008, 49, 2216.
19. Loh, T. P.; Pei, J.; Cao, G. Q. Chem. Commun. 1996, 1819.
20. (a) Li, Z.; Zhang, J.; Li, C. J. Tetrahedron Lett. 2003, 44, 153; (b) Zhang, J.; Li, C. J.
J. Org. Chem. 2002, 67, 3969; (c) Babu, G.; Perumal, P. T. Tetrahedron Lett. 1997,
38, 5025.
Acknowledgements
One of the authors, S.S. is thankful to Council of Scientific and
Industrial Research, New Delhi, India, for financial assistance in the
form of senior research fellowship. Financial assistances from
Michigan Diagnostics L.L.C., Michigan USA and Department of Sci-
ence and Technology (DST), New Delhi, are gratefullyacknowledged.
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