Efficient synthesis of 12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthen-11-one derivatives catalyzed by p-dodecylbenzenesulfonic acid in aqueous media under ultrasound irradiation

Article abstract of DOI:10.1080/00397911.2011.555048

An efficient synthesis of 12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthen-11- one derivatives via the three-component condensation of aromatic aldehyde, 2-naphthol, and 5,5-dimethyl-1,3-cyclohexanedione was carried out in 76-93% yields at 40-42C using p-dodec

Full text of DOI:10.1080/00397911.2011.555048

Synthetic Communications1, 42: 2161–2170, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.555048
EFFICIENT SYNTHESIS OF 12-ARYL-8,9,10,12-
TETRAHYDROBENZO[a]XANTHEN-11-ONE
DERIVATIVES CATALYZED BY p-
DODECYLBENZENESULFONIC ACID IN AQUEOUS
MEDIA UNDER ULTRASOUND IRRADIATION
Ji-Tai Li,1 Yan-Wei Li,1 and Ya-Li Song2
1Key Laboratory of Analytical Science and Technology of Hebei Province,
Key Laboratory of Medical Chemistry and Molecular Diagnosis,
Ministry of Education, College of Chemistry and Environmental Science,
Hebei University, Baoding, China
2College of Pharmaceutical Science, Hebei University, Baoding, China
GRAPHICAL ABSTRACT
Abstract An efficient synthesis of 12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthen-11-one
derivatives via the three-component condensation of aromatic aldehyde, 2-naphthol, and
5,5-dimethyl-1,3-cyclohexanedione was carried out in 76–93% yields at 40–42 ꢀC using
p-dodecylbenzenesulfonic acid as catalyst in aqueous media under ultrasound irradiation.
Keywords Aqueous media; three-component condensation; ultrasound irradiation;
xanthene
INTRODUCTION
Xanthenes and benzoxanthenes are important biologically active heterocyclic
compounds that possess antiviral,[1] antibacterial[2] and anti-inflammatory activities.[3]
These compounds can be used as dyes,[4,5] as pH-sensitive fluorescent materials,[6] and
in laser technology.[7] Synthesis of these compounds via three-component conden-
sation of aldehyde, 2-naphthol, and cyclic 1,3-dicarbonyl compounds was carried
out under different conditions, such as solvent-free reaction catalyzed by HBF4=
SiO2,[8] I2,[9] para-toluenesulfonic acid (p-TSA),[10,11] InCl3, P2O5,[12] Zr(HSO4)4,[13]
Received October 13, 2010.
Address correspondence to Ji-Tai Li, Key Laboratory of Analytical Science and Technology
of Hebei Province, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis, Ministry
of Education, College of Chemistry and Environmental Science, Hebei University, Wusi East Road
No. 180, Baoding 071002, China. E-mail: lijitai@hbu.cn
2161

2162
J.-T. LI, Y.-W. LI, AND Y.-L. SONG
Scheme 1. Synthesis of 12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthen-11-one derivatives.
H3PW12O40,[14] cyanuric chloride,[15] HClO4-SiO2,[16] ceric ammonium nitrate
(CAN),[17] and refluxing in 1,2-dichloroethane catalyzed by Sr(OTf)2
or
[18]
NaHSO4 ꢁ SiO2.[19] However, in spite of their potential utility, some of the reported
methods suffer from some drawbacks, such as longer reaction time, expensive
transition-metal catalyst, or organic solvent.
Organic reactions in aqueous media have attracted increasing interest because
of environmental issues and the understanding of biochemical processes. Water,
being the cheapest and most nontoxic solvent, is known as a ‘‘green’’ solvent.[20]
Many organic reactions can be carried out in water.[21] The condensations of
aldehyde, naphthol, and cyclic 1,3-dicarbonyl compounds catalyzed by tetrabutyl
ammonium fluoride[22] or praline triflate[23] in refluxing aqueous solution have been
reported, but some reactions needed a long reaction time.
p-Dodecylbenzenesulfonic acid (DBSA), as a Brønsted acid–surfactant com-
bined catalyst, acts both as an acid catalyst to activate a substrate and as a surfactant
to form stable colloidal dispersion with water-insoluble substrates.[24] This catalyst
has been successfully used in many organic reactions.[25]
Ultrasound has been considered a useful protocol in organic synthesis in the
past three decades.[26–28] Compared with traditional methods, this procedure is more
convenient. A large number of organic reactions can be carried out in greater yield,
shorter reaction time, or mild conditions under ultrasound.[29,30] The condensation
of arylaldehyde, 2-naphthol, and 5,5-dimethyl-1,3-cyclohexanedione catalyzed by
p-TSA has been reported to give a good results at 70 ꢀC with sonication.[11] Herein,
we report a practical and efficient synthesis of 12-aryl-8,9,10,12-tetrahydrobenzo[a]
xanthen-11-one derivatives using DBSA as catalyst in aqueous media under ultra-
sound irradiation (Scheme 1).
RESULTS AND DISCUSSION
To optimize the reaction conditions, the condensation of benzaldehyde,
2-naphthol, and 5,5-dimethyl-1,3-cyclohexanedione was selected as the model under
ultrasound irradiation (Table 1).
The effects of the amount of DBSA on the reaction was observed. When the
amounts of DBSA were 0.05 mmol, 0.075 mmol and 0.1 mmol, the yields of 4a were
82% (entry 4), 88% (entry 3) and 93% (entry 2), respectively. Increasing the amount
of DBSA to 0.2 mmol, did not improve either the yield or the reaction time
compared with 0.1 mmol (entry 1). In the absence of DBSA, three-component
condensation was carried out with 11% yield at 40–42 ꢀC in 80 min under ultrasound
(entry 5). In the presence of DBSA (0.1 mmol) with the same reaction time and

SYNTHESIS OF TETRAHYDROBENZO[A]XANTHEN-11-ONE
2163
Table 1. Effect of reaction conditions on the synthesis of 4a under ultrasound irradiationa
Amount of
DBSA (mmol)
Isolated
yield (%)
Entry
Frequency (kHz)
Temp. (ꢀC)
Time (min)
1
2
0.2
0.1
0.075
0.05
0
40
40
40
40
40
40
25
—
40
40
40
40–42
40–42
40–42
40–42
40–42
30–33
40–42
40–42
40–42
40–42
40–42
80
80
93
93
3
80
90
88
82
4
5
80
11
91
6
0.1
0.1
0.1
0.1
0.1
0.1
200
80
7
89
8
130
60
85b
71c
90d
91e
9
10
11
120
120
aSubstrate: benzaldehyde, 1 mmol; 2-naphthol, 1 mmol; 5,5-dimethyl-1,3-cyclohexanedione, 1.2 mmol;
water 2 mL.
bStirring alone without ultrasound.
cSolvent-free.
dEthanol as solvent. The product is 3-ethoxy-5,5-dimethylcyclohex-2-enone.
eMethanol as solvent. The product is 3-methoxy-5,5-dimethylcyclohex-2-enone.
temperature, 4a was obtained in 93% yield (entry 2). It is shown that DBSA has a
significant effect on the reaction.
As shown in Table 1, the temperature had a significant effect on the reaction time,
but the effect on the yield was not obvious. When the reaction was carried out at
30–33 ꢀC, it took 200 min and gave 91% yield (entry 6), but when the temperature
was 40–42 ꢀC, the reaction time was shortened to 80 min and the yield was 93% (entry 2).
The effect of frequency of ultrasound irradiation on the reaction was also
observed. The yield of 4a with 40 kHz irradiation for 80 min (entry 2) is better than
that with 25 kHz irradiation for 80 min (entry 7). We also did the experiment in the
absence of ultrasound; the condensation of benzaldehyde, 2-naphthol and 5,5-
dimethyl-1,3-cyclohexanedione was carried out with 85% yield (entry 8) using stirring
alone in 130 min. In the presence of ultrasound, the desired product (4a) was obtained
in 93% yield within 80 min. It is apparent that the reaction can be finished in a shorter
reaction time to give better yield under ultrasound irradiation.
We also examined the effect of solvent or solvent-free conditions on the conden-
sation under ultrasound. When the reaction was carried out in ethanol or methanol,
the condensation of 5,5-dimethyl-1,3-cyclohexanedione with ethanol or methanol
was performed, and no formation of the corresponding title compound was observed.
Under solvent-free conditions, 4a was obtained in 71% yield (Table 1, entry 9).
From these results the optimum reaction conditions were chosen: aldehyde (1,
1 mmol), 2-naphthol (2, 1 mmol), 5,5-dimethyl-1,3-cyclohexanedione (3, 1.2 mmol),
DBSA (0.1 mmol), water (2 mL), ultrasound frequency 40 kHz, and reaction
temperature 40–42 ꢀC. Using this reaction system, a series of experiments for the
syntheses of 4a–o were carried out under ultrasound at 40–42 ꢀC. The results are
summarized in Table 2.
As shown in Table 2, the condensation of aromatic aldehyde, 2-naphthol, and
5,5-dimethyl-1,3-cyclohexanedione was carried out with good yields catalyzed by

2164
J.-T. LI, Y.-W. LI, AND Y.-L. SONG
DBSA in aqueous media under ultrasound irradiation. From these results, we can
deduce that the yields are in general similar or greater than those described in the
literature.[8–19,22,23] For example, in the previous report,[22] the condensation of
4-chlorobenzaldehyde, 2-naphthol, and 5,5-dimethyl-1,3-cyclohexanedione catalyzed
by TBAF at refluxing temperature in water for 3.5 h, the yield of 4 h was 92%, whereas
present procedure needed only 100 min to give 4 h in 92% yield (Table 2, entry h). In
the reaction catalyzed by NaHSO4 ꢁ SiO2,[19] the condensation of benzaldehyde,
2-naphthol, and 5,5-dimethyl-1,3-cyclohexanedione was carried out with 87% yield
under refluxing 1,2-dichloroethane for 4 h, whereas the present procedure offered
the target product in 93% yield under ultrasound for 80 min (Table 2, entry a).
To verify the effect of ultrasound irradiation, several reactions were performed
by stirring alone under conditions with no ultrasound at 40–42 ꢀC. As shown in
Table 2, 4d, 4 h, 4i, 4 l, and 4n were obtained in 76%, 82%, 64%, 78%, and 77%, yields
within 220 min, 210 min, 120 min, 180 min, and 240 min respectively, whereas under
ultrasound irradiation 4d, 4 h, 4i, 4 l, and 4n were obtained in 87%, 92%, 79%, 84%
and 82% yields within 140 min, 100 min, 60 min, 100 min, and 120 min respectively
(Table 2, entries d, h, i, l, and n). It is clear that ultrasound can reduce reaction time
and increase the reaction yield.
It is noted that when heterocyclic aldehydes, such as 2-furaldehyde, 2-pyridyl-
aldehyde, 4-pyridylaldehyde or 3-indolealdehyde, were used as substrate, no reactions
were observed by thin-layer chrometography (TLC). While cinnamaldehyde was used
as substrate, the condensation of cinnamaldehyde and 5,5-dimethyl-1,3-cyclohexane-
dione took place to obtain 3,3,6,6-tetramethyl-9-(2-phenyl-ethylene)-1,8-dioxo-
octahydroxanthene in 83% yield. It is shown that the present method has some limita-
tions for some aliphatic aldehydes and heterocyclic aldehydes. When Meldrum’s acid
Table 2. Synthesis of 4a–o catalyzed by DBSA in aqueous media at 40–42 ꢀC under ultrasound
irradiationa
Time (min)
(stirb)
Isolated yield
(%) (stirb)
Entry
R
Product
Mp (ꢀC)
a
b
c
d
e
f
C6H5
80 (130)
120
120
4a
4b
4c
4d
4e
4f
93 (85)
93
90
151–152 (151–153)[12]
174–175 (175–176)[9]
165–167 (163–165)[12]
212–213 (211–212)[18]
150–151 (150–151)[19]
178–179 (179–180)[12]
178–180 (180–181)[11]
179–181 (180–182)[12]
212–213 (213–215)[12]
166–167 (164–166)[11]
169–170 (168–170)[12]
170–171 (175–176)[9]
183–184 (178–180)[12]
177–178
4-CH3C6H4
2-CH3OC6H4
4-CH3OC6H4
4-OH C6H4
2-ClC6H4
140 (220)
90
120
87 (76)
81
87
g
h
i
3-ClC6H4
4-ClC6H4
130
4g
4h
4i
80
100 (210)
60 (120)
110
92 (82)
79 (64)
76
2-HO-3-CH3OC6H3
4-HO-3-CH3OC6H3
3-NO2C6H4
4-NO2C6H4
2,4-Cl2C6H3
3,4-Cl2C6H3
CH3
j
4j
k
l
100
100 (180)
120
4k
4l
80
84 (78)
82
m
n
o
4m
4n
4o
120 (240)
240
82 (77)
63
110–111
aSubstrate: aryl aldehyde, 1 mmol; 2-naphthol, 1 mmol; 5,5-dimethyl-1,3-cyclohexanedione,
1.2 mmol; DBSA, 0.1 mmol; H2O, 2 mL.
bStirring alone without ultrasound.

SYNTHESIS OF TETRAHYDROBENZO[A]XANTHEN-11-ONE
2165
Table 3. Comparison with the methods in aqueous media reported in literaturesa
Entry
Catalyst
Time (min)
Temperature (ꢀC)
Yield (%)
1
2
3
4
5
p-DBSA
80
540
300
180
300
40–42 (ultrasound)
100
reflux
93
Tetrabutylammonium fluoride
Proline triflate
p-TSA
99[22]
79b[23]
30[11]
Nr[18]
70 (ultrasound)
80
Sr(OTf)2
aCondensation of benzaldehyde, 2-naphthol, and 5,5-dimethyl-1,3-cyclohexanedione.
bCondensation of benzaldehyde, 1-naphthol, and 5,5-dimethyl-1,3-cyclohexanedione.
was used instead of 5,5-dimethyl-1,3-cyclohexanedione, the condensation did not
occur at all.
The comparison with other methods in aqueous media reported in literature is
shown in Table 3. From these results, we can deduce that the yield is in general simi-
lar or better than those described in the literature. Compared with the reported
methods, the main advantage of the procedure are greater yield, milder conditions,
and shorter reaction time.
CONCLUSION
In conclusion, we have found an efficient procedure for the synthesis of
12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthen-11-one derivatives via the conden-
sation of aromatic aldehyde, 2-naphthol, and 5,5-dimethyl-1,3-cyclohexanedione
catalyzed by DBSA in aqueous media under ultrasound irradiation. The procedure
described here is simple, mild, efficient, and environmentally friendly.
EXPERIMENTAL
1
Melting points are uncorrected. The H NMR and 13C NMR spectra were
recorded on a Bruker Avance 600 (600-MHz) spectrometer using tetramethylsilane
(TMS) as internal standard and CDCl3 as solvent. Mass spectra (MS) were deter-
mined on a Bruker Apex Ultra 7.0 T spectrometer. Sonication was performed in a
Shanghai Branson-BUG40-06 ultrasonic cleaner (with a frequency of 40 kHz and a
nominal power of 250 W). The reaction flask was located in the ultrasonic bath, where
the surface of reactants is slightly lower than the level of the water. The reaction
temperature was controlled by addition or removal of water from ultrasonic bath.
General Procedure for the Synthesis of 4a–o
A 25-mL Erlenmeyer flask was charged with aldehydes (1, 1 mmol), 2-naphthol
(2, 1 mmol), 5,5-dimethyl-1,3-cyclohexanedione (3, 1.2 mmol), DBSA (0.1 mmol),
and water (2 mL). The reaction flask was irradiated in the water bath of the ultrasonic
cleaner at 40–42 ꢀC (bath temperature; the temperature inside the reactor was also
40–42 ꢀC) for the period of time as indicated in Table 2. The reaction was monitored
by TLC. After completion of the reaction, the mixture was diluted with water
(10 mL), and the solid was filtered, washed with water, and dried to give the crude

2166
J.-T. LI, Y.-W. LI, AND Y.-L. SONG
product, which was further purified by column chromatography on silica gel (200–300
mesh) eluted with petroleum ether or a mixture of petroleum ether and ethyl acetate
to offer pure product 4a–o. The authenticity of the product 4n–o was established by
1H NMR, 13 C NMR, and MS; the rest of the known compounds (4a–m) were estab-
1
lished by H NMR and their melting points compared with those reported in the
literature.
9,9-Dimethyl-12-phenyl-8,9,10,12-tetrahydrobenzo[a]xanthen-11-
one (4a)
1
White solid. H NMR: dH 0.95 (s, 3H, CH3), 1.11 (s, 3H, CH3), 2.24 (d, J ¼
16.3 Hz, 1H, CH2), 2.30 (d, J ¼ 16.3 Hz, 1H, CH2), 2.56 (s, 2H, CH2), 5.70 (s, 1H,
CH), 7.03–7.06 (m, 1H, Ph-H), 7.15–7.17 (m, 2H, Ph-H), 7.31–7.34 (m, 4H, Ph-H),
7.40–7.43 (m, 1H, Ph-H), 7.76 (t, J ¼ 9.2 Hz, 2H, Ph-H), 7.98 (d, J ¼ 8.4 Hz, 1 H,
Ph-H).
9,9-Dimethyl-12-(4-methylphenyl)-8,9,10,12-tetrahydrobenzo[a]-
xanthen-11-one (4b)
1
White solid. H NMR: dH 0.97 (s, 3H, CH3), 1.11 (s, 3H, CH3), 2.19 (s, 3H,
CH3), 2.24 (d, J ¼ 16.2 Hz, 1H, CH2), 2.30 (d, J ¼ 16.2 Hz, 1H, CH2), 2.56 (s, 2H,
CH2), 5.66 (s, 1H, CH), 6.96 (d, J ¼ 7.9 Hz, 2H, Ph-H), 7.21–7.22 (m, 2H, Ph-H),
7.31 (d, J ¼ 8.9 Hz, 1H, Ph-H), 7.34–7.37 (m, 1H, Ph-H), 7.41–7.44 (m, 1H,
Ph-H), 7.74 (d, J ¼ 8.9 Hz, 1H, Ph-H), 7.76 (d, J ¼ 7.9 Hz, 1H, Ph-H), 8.0 (d, J ¼
8.5 Hz, 1H, Ph-H)
12-(2-Methoxyphenyl)-9,9-dimethyl-8,9,10,12-tetrahydrobenzo[a]-
xanthen-11-one (4c)
1
White solid. H NMR: dH 1.00 (s, 3H, CH3), 1.12 (s, 3H, CH3), 2.20 (dd,
J ¼ 16.2 Hz, J ¼ 1.0 Hz, 1H, CH2), 2.29 (d, J ¼ 16.2 Hz, 1H, CH2), 2.55-2.62 (m,
2H, CH2), 3.94 (s, 3H, CH3), 5.96 (s, 1H, CH), 6.76–6.81 (m, 2H, Ph-H),
7.02–7.05 (m, 1H, Ph-H), 7.25–7.27 (m, 2H, Ph-H), 7.33–7.35 (m, 1H, Ph-H),
7.41–7.44 (m, 1H, Ph-H), 7.69 (d, J ¼ 8.9 Hz, 1H, Ph-H), 7.73 (d, J ¼ 7.9 Hz, 1H,
Ph-H), 8.28 (d, J ¼ 8.5 Hz, 1H, Ph-H).
12-(4-Methoxyphenyl)-9,9-dimethyl-8,9,10,12-tetrahydrobenzo[a]-
xanthen-11-one (4d)
White solid. 1H NMR: dH 0.97 (s, 3H, CH3), 1.11 (s, 3H, CH3), 2.24 (d,
J ¼ 16.3 Hz, 1H, CH2), 2.30 (d, J ¼ 16.3 Hz, 1H, CH2), 2.55 (s, 2H, CH2), 3.68 (s,
3H, CH3), 5.65 (s, 1H, CH), 6.69–6.71 (m, 2H, Ph-H), 7.23–7.25 (m, 2H, Ph-H),
7.30 (d, J ¼ 8.9 Hz, 1H, Ph-H), 7.35-7.37 (m, 1H, Ph-H), 7.41-7.44 (m, 1H, Ph-H),
7.74 (d, J ¼ 8.9 Hz, 1H, Ph-H), 7.76 (d, J ¼ 7.9 Hz, 1H, Ph-H), 7.98 (d, J ¼ 8.5 Hz,
1H, Ph-H).

SYNTHESIS OF TETRAHYDROBENZO[A]XANTHEN-11-ONE
2167
12-(4-Hydroxyphenyl)-9,9-dimethyl-8,9,10,12-tetrahydrobenzo[a]-
xanthen-11-one (4e)
1
White solid. H NMR: dH 0.96 (s, 3H, CH3), 1.10 (s, 3H, CH3), 2.26 (d,
J ¼ 16.3 Hz, 1H, CH2), 2.31 (d, J ¼ 16.3 Hz, 1H, CH2), 2.56 (s, 2H, CH2), 5.63 (s,
1H, CH), 6.14 (s, 1H, OH), 6.59 (d, J ¼ 8.6 Hz, 2H, Ph-H), 7.15–7.43 (m, 5H,
Ph-H), 7.74 (d, J ¼ 8.9 Hz, 1H, Ph-H), 7.77 (d, J ¼ 7.9 Hz, 1H, Ph-H), 7.97 (d,
J ¼ 8.4 Hz, 1H, Ph-H).
12-(2-Chlorophenyl)-9,9-dimethyl-8,9,10,12-tetrahydrobenzo[a]-
xanthen-11-one (4f)
1
White solid. H NMR: dH 1.00 (s, 3H, CH3), 1.14 (s, 3H, CH3), 2.26 (d,
J ¼ 16.3 Hz, 1H, CH2), 2.31 (d, J ¼ 16.3 Hz, 1H, CH2), 2.60 (q, J ¼ 17.4 Hz,
J ¼ 3.9 Hz, 2H, CH2), 5.99 (s, 1H, CH), 6.97–7.00 (m, 1H, Ph-H), 7.05 (t, J ¼ 7.1 Hz,
Hz, 1H, Ph-H), 7.26–7.30 (m, 3H, Ph-H), 7.38 (t, J ¼ 7.2 Hz, 1H, Ph-H), 7.48 (t,
J ¼ 7.1 Hz, 1H, Ph-H), 7.75 (t, J ¼ 9.1 Hz, 2H, Ph-H), 8.22 (d, J ¼ 8.5 Hz, 1H, Ph-H).
12-(3-Chlorophenyl)-9,9-dimethyl-8,9,10,12-tetrahydrobenzo[a]-
xanthen-11-one (4g)
1
White solid. H NMR: dH 0.98 (s, 3H, CH3), 1.12 (s, 3H, CH3), 2.26 (d,
J ¼ 16.3 Hz, 1H, CH2), 2.31 (d, J ¼ 16.3 Hz, 1H, CH2), 2.58 (q, J ¼ 17.4 Hz, 2H,
CH2), 5.69 (s, 1H, CH), 7.02–7.04 (m, 1H, Ph-H), 7.11 (t, J ¼ 7.9 Hz, 1H, Ph-H),
7.25–7.29 (m, 2H, Ph-H), 7.33 (d, J ¼ 8.9 Hz, 1H, Ph-H), 7.38–7.40 (m, 1H,
Ph-H), 7.44–7.46 (m, 1H, Ph-H), 7.79 (t, J ¼ 7.7 Hz, 2H, Ph-H), 7.92 (d, J ¼ 8.5 Hz,
Hz, 1H, Ph-H).
12-(4-Chlorophenyl)-9,9-dimethyl-8,9,10,12-tetrahydrobenzo[a]-
xanthen-11-one (4h)
1
White solid. H NMR: dH 0.96 (s, 3H, CH3), 1.11 (s, 3H, CH3), 2.24 (d,
J ¼ 16.3 Hz, 1H, CH2), 2.30 (d, J ¼ 16.3 Hz, 1H, CH2), 2.56 (s, 2H, CH2), 5.68 (s,
1H, CH), 7.12–7.14 (m, 2H, Ph-H), 7.26–7.28 (m, 2H, Ph-H), 7.31 (d, J ¼ 8.9 Hz,
1H, Ph-H), 7.37–7.39 (m, 1H, Ph-H), 7.42–7.44 (m, 1H, Ph-H), 7.77 (t, J ¼ 8.6 Hz,
2H, Ph-H), 7.90 (d, J ¼ 8.5 Hz, 1H, Ph-H).
12-(2-Hydroxy-3-methoxyphenyl)-9,9-dimethyl-8,9,10,12-
tetrahydrobenzo[a]xanthen-11-one (4i)
1
White solid. H NMR: dH 0.99 (s, 3H, CH3), 1.13 (s, 3H, CH3), 2.32 (d,
J ¼ 16.5 Hz, 1H, CH2), 2.39 (d, J ¼ 16.3 Hz, 1H, CH2), 2.59 (s, 2H, CH2), 3.85 (s,
3H, CH3), 5.82 (s, 1H, CH), 6.32 (dd, J ¼ 7.5 Hz, J ¼ 1.3 Hz, 1H, Ph-H), 6.56–6.61
(m, 2H, Ph-H), 7.26–7.42 (m, 3H, Ph-H), 7.75 (d, J ¼ 9.2 Hz, 2H, Ph-H), 7.83 (d,
J ¼ 8.4 Hz, 1H, Ph-H), 8.67 (s, 1H, OH).

2168
J.-T. LI, Y.-W. LI, AND Y.-L. SONG
12-(4-Hydroxy-3-methoxyphenyl)-9,9-dimethyl-8,9,10,12-
tetrahydrobenzo[a]xanthen-11-one (4j)
White solid. 1H NMR: dH 0.98 (s, 3H, CH3), 1.11 (s, 3H, CH3), 2.26 (d,
J ¼ 16.3 Hz, 1H, CH2), 2.30 (d, J ¼ 16.3 Hz, 1H, CH2), 2.55 (s, 2H, CH2), 3.82 (s,
3H, CH3), 5.44 (s, 1H, OH), 5.64 (s, 1H, CH), 6.63–6.68 (m, 2H, Ph-H), 7.00 (d,
J ¼ 1.9 Hz, 1H, Ph-H), 7.31 (d, J ¼ 8.9 Hz, 1H, Ph-H), 7.36-7.39 (m, 1H, Ph-H),
7.42–7.44 (m, 1H, Ph-H), 7.75 (d, J ¼ 8.9 Hz, 1H, Ph-H), 7.78 (d, J ¼ 7.6 Hz, 1H,
Ph-H), 7.98 (d, J ¼ 8.3 Hz, 1H, Ph-H).
9,9-Dimethyl-12-(3-nitrophenyl)-8,9,10,12-tetrahydrobenzo[a]-
xanthen-11-one (4k)
White solid. 1H NMR: dH 0.95 (s, 3H, CH3), 1.13 (s, 3H, CH3), 2.24 (d,
J ¼ 16.3 Hz, 1H, CH2), 2.33 (d, J ¼ 16.3 Hz, 1H, CH2), 2.61 (s, 2H, CH2), 5.82 (s,
1H, CH), 7.35–7.46 (m, 4H, Ph-H), 7.79–7.82 (m, 3H, Ph-H), 7.86 (d, J ¼ 8.2 Hz,
1H, Ph-H), 7.92–7.94 (m, 1H, Ph-H), 8.11 (s, 1H, Ph-H).
9,9-Dimethyl-12-(4-nitrophenyl)-8,9,10,12-tetrahydrobenzo[a]-
xanthen-11-one (4l)
White solid. 1H NMR: dH 0.94 (s, 3H, CH3), 1.13 (s, 3H, CH3), 2.24 (d,
J ¼ 16.3 Hz, 1H, CH2), 2.32 (d, J ¼ 16.3 Hz, 1H, CH2), 2.59 (q, J ¼ 17.6 Hz,
J ¼ 3.8 Hz, 2H, CH2), 5.81 (s, 1H, CH), 7.35 (d, J ¼ 8.9 Hz, 1H, Ph-H), 7.38–7.41
(m, 1H, Ph-H), 7.42–7.45 (m, 1H, Ph-H), 7.50–7.52 (m, 2H, Ph-H), 7.79–7.83 (m,
3H, Ph-H), 8.02–8.04 (m, 2H, Ph-H)
12-(2,4-Dichlorophenyl)-9,9-dimethyl-8,9,10,12-tetrahydrobenzo[a]-
xanthen-11-one (4m)
White solid. 1H NMR dH 1.00 (s, 3H, CH3), 1.13 (s, 3H, CH3), 2.22 (d,
J ¼ 16.3 Hz, 1H, CH2), 2.31 (d, J ¼ 16.3 Hz, 1H, CH2), 2.60 (q, J ¼ 17.4 Hz,
J ¼ 7.26 Hz, 2H, CH2), 5.93 (s, 1H, CH), 7.03 (dd, J ¼ 8.4 Hz, J ¼ 1.8 Hz, 1H,
Ph-H), 7.21–7.28 (m, 3H, Ph-H), 7.39 (t, J ¼ 7.3 Hz, 1H, Ph-H), 7.48 (t, J ¼ 7.2 Hz,
Hz, 1H, Ph-H), 7.75 (t, J ¼ 8.9 Hz, 2H, Ph-H), 8.12 (d, J ¼ 8.5 Hz, 1H, Ph-H)
12-(3,4-Dichlorophenyl)-9,9-dimethyl-8,9,10,12-tetrahydrobenzo[a]-
xanthen-11-one (4n)
1
White solid. H NMR: dH: 0.98 (s, 3H, CH3), 1.12 (s, 3H, CH3), 2.26 (d,
J ¼ 16.3 Hz, 1H, CH2), 2.31 (d, J ¼ 16.3 Hz, 1H, CH2), 2.58 (s, 2H, CH2), 5.67 (s,
1H, CH), 7.21–7.25 (m, 2H, Ph-H), 7.33 (d, J ¼ 8.9 Hz, 1H, Ph-H), 7.37 (s, 1H,
Ph-H), 7.39–7.42 (m, 1H, Ph-H), 7.44–7.47 (m, 1H, Ph-H), 7.80 (t, J ¼ 6.5 Hz, 2H,
Ph-H), 7.86 (d, J ¼ 8.5 Hz, 1H, Ph-H); 13C NMR: dc 196.74, 164.30, 147.81,
144.94, 132.29, 131.57, 131.10, 130.31, 130.15, 129.41, 128.60, 128.01, 127.31,
125.16, 123.29, 117.10, 116.34, 113.36, 50.84, 41.41, 34.11, 32.29, 29.22, 27.25 ppm;
m=z (ESI): 423 [M]þ.

SYNTHESIS OF TETRAHYDROBENZO[A]XANTHEN-11-ONE
2169
12-Methyl-9,9-dimethyl-8,9,10,12-tetrahydrobenzo[a]xanthen-
11-one (4o)
1
White solid. H NMR dH: 1.14 (s, 3H, CH3), 1.17 (s, 3H, CH3), 1.37 (d,
J ¼ 6.6 Hz, 3H, CH3), 2.36 (d, J ¼ 3.0 Hz, 2H, CH2), 2.51 (s, 2H, CH2), 4.58 (q,
J ¼ 6.6 Hz, J ¼ 6.6 Hz, 1H, CH), 7.19 (d, J ¼ 8.8 Hz, 1H, Ph-H), 7.43 (t, J ¼ 7.5 Hz,
1H, Ph-H), 7.54 (t, J ¼ 7.6 Hz, 1H, Ph-H), 7.69 (d, J ¼ 8.8 Hz,1H, Ph-H), 7.80 (d,
J ¼ 8.1 Hz 1H, Ph-H), 8.08 (d, J ¼ 8.5 Hz 1H, Ph-H); 13C NMR: dc 197.49, 164.94,
147.32, 131.43, 131.17, 128.59, 128.03, 126.84, 124.81, 123.05, 110.99, 117.07,
114.65, 51.04, 41.36, 32.23, 29.47, 27.19, 23.37, 23.00 ppm; m=z (ESI): 315 [MþNa]þ
ACKNOWLEDGMENT
We thank the Natural Science Foundation of Hebei Province (B2006000969),
China, for financial support.
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