Synthesis and cytotoxicity of 9-substituted benzo[de]chromene-7,8-dione and 5-benzyl-9-substituted benzo[de]chromene-7,8-dione

Article abstract of DOI:10.1080/00397910600764683

New Mansonone analogues of 9-substitued benzo[de]chromene-7,8-dione 5b-e and 5-benzyl-9-substitued benzo[de]chromene-7,8-dione 6a-e were prepared through a modified route. The first step involved a bulky base t-butylamine mediated regioselective deacetylation of 2-substituted-1,4-naphth-diyl diacetate, resulting in obtaining of monoacetate 4-acetate 2 in high yield. The mechanism of cyclization, debenzylation, and oxidation for the formation of 5a-e and 6a-e were discussed. The cytotoxicity of the prepared compounds 5 and 6 were comparable with naturally occurring Mansonone F. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910600764683

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Synthesis and Cytotoxicity of 9‐Substituted
Benzo[de]chromene‐7,8‐dione
and 5‐Benzyl‐9‐substituted
Benzo[de]chromene‐7,8‐dione
Shi‐Liang Huang a b , Yi Luo a , Zhi‐Shu Huang a , Xing‐Yuan Wang a b
,
Xian‐Zhang Bu a , Pei‐Qing Liu a , Lin Ma b , Bing‐Fen Xie c , Zong‐Chao Liu c
Yue‐Ming Li d & Albert S. C. Chan d
,
a School of Pharmaceutical Science , Sun Yat‐Sen University , Guangzhou,
China
b School of Chemistry and Chemical Engineering , Sun Yat‐Sen University ,
Guangzhou, China
c Cancer Research Center , Sun Yat‐Sen University , Guangzhou, China
d Department of Applied Biology and Chemical Technology , Hong Kong
Polytechnic University , Kowloon, Hong Kong
Published online: 16 Feb 2007.
To cite this article: Shi‐Liang Huang , Yi Luo , Zhi‐Shu Huang , Xing‐Yuan Wang , Xian‐Zhang Bu , Pei‐Qing
Liu , Lin Ma , Bing‐Fen Xie , Zong‐Chao Liu , Yue‐Ming Li & Albert S. C. Chan (2006) Synthesis and Cytotoxicity
of 9‐Substituted Benzo[de]chromene‐7,8‐dione and 5‐Benzyl‐9‐substituted Benzo[de]chromene‐7,8‐dione,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
36:18, 2667-2684, DOI: 10.1080/00397910600764683
To link to this article: http://dx.doi.org/10.1080/00397910600764683
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Synthetic Communicationsw, 36: 2667–2684, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600764683
Synthesis and Cytotoxicity of 9-Substituted
Benzo[de]chromene-7,8-dione and 5-Benzyl-
9-substituted Benzo[de]chromene-7,8-dione
Shi-Liang Huang
School of Pharmaceutical Science and School of Chemistry and Chemical
Engineering, Sun Yat-Sen University, Guangzhou, China
Yi Luo and Zhi-Shu Huang
School of Pharmaceutical Science, Sun Yat-Sen University,
Guangzhou, China
Xing-Yuan Wang
School of Pharmaceutical Science and School of Chemistry and Chemical
Engineering, Sun Yat-Sen University, Guangzhou, China
Xian-Zhang Bu and Pei-Qing Liu
School of Pharmaceutical Science, Sun Yat-Sen University,
Guangzhou, China
Lin Ma
School of Chemistry and Chemical Engineering, Sun Yat-Sen University,
Guangzhou, China
Bing-Fen Xie and Zong-Chao Liu
Cancer Research Center, Sun Yat-Sen University, Guangzhou, China
Yue-Ming Li and Albert S. C. Chan
Department of Applied Biology and Chemical Technology, Hong Kong
Polytechnic University, Kowloon, Hong Kong
Received in Japan February 24, 2006
Address correspondence to Zhi-Shu Huang, School of Pharmaceutical Science, Sun
Yat-Sen University, Guangzhou, 510080, China. E-mail: huangzhishu@hotmail.com
2667

2668
S.-L. Huang et al.
Lian-Quan Gu
School of Pharmaceutical Science and School of Chemistry and Chemical
Engineering, Sun Yat-Sen University, Guangzhou, China
Abstract: New Mansonone analogues of 9-substitued benzo[de]chromene-7,8-dione
5b–e and 5-benzyl-9-substitued benzo[de]chromene-7,8-dione 6a–e were prepared
through a modified route. The first step involved a bulky base t-butylamine mediated
regioselective deacetylation of 2-substituted-1,4-naphth-diyl diacetate, resulting in
obtaining of monoacetate 4-acetate 2 in high yield. The mechanism of cyclization,
debenzylation, and oxidation for the formation of 5a–e and 6a–e were discussed.
The cytotoxicity of the prepared compounds 5 and 6 were comparable with naturally
occurring Mansonone F.
Keywords: Antitumor, mansonone F, oxidation debenzyl rearrangement, selective
hydrolization
INTRODUCTION
Mansonone compounds represent a series of naturally occurring o-quinones
mainly isolated from the heartwood of Mansonia altissima and Ulmus
glabra. This type of compound is classified as phytoalexin, which is
produced and accumulated in plants in response to bacteria and fungi infec-
tions and is used to treat Dutch elm disease (DED). Mansonone F contained
the oxaphenalene skeleton, which is a relatively novel structure and rarely
exists in natural products (Fig. 1). This compound had shown comprehensive
phamacological activities such as antibacterial and antitumor activity.[1–3]
The limited source as well as the difficult synthesis of this compound
prompted us to develop a facile synthetic route to prepare the Mansonone F
analogues and to optimize their structure for enhancing bioactivity.[4–7]
A series of Mansonone F analogues bearing 9-substituted benzo[de]chro-
mene-7,8-dione skeletons were prepared through a modified route. The first
step involved a bulky base t-butylamine-mediated regioselective deacetylation
of 2-substituted-1,4-naphth-diyl diacetate, resulting in obtaining monoacetate
Figure 1. Mansonone F.

9-Substituted Benzo[de]chromene-7,8-dione
2669
4-acetate 2 in high yield. The mechanism of cyclization, debenzylation, and
oxidation for the formation of 5a–e and 6a–e were discussed. The cytotoxicity
and the structure–activity relationship of the prepared compounds were studied.
RESULTS AND DISCUSSION
9-Substitued benzo[de]chromene-7,8-dione was synthesized as shown in
Scheme 1. This route started from 2-substituted 1,4-naphenol diester 1,
which is easily commercially available. Alternatively, it could be conveniently
prepared through a free radical alkylation.[8,9] Thus, in the presence of a bulky
base t-BuNH2, the deacetylation took place regioselectively and gave the
corresponding monoacetate 2 in high yield (75–92%). Benzylation of the
phenolic hydroxyl group produced compound 3 and subsequently removed
the remaining acetyl group; treatment of the crude product with
ClCH2COCH3 in the presence of K2CO3/KI gave compound 4 in high yield.
After further electrophilc cyclization (in the presence of HBF4), debenzylation
and oxidation (with Se2O) yielded the final products of 5a–e. Accidentally,
5-benzyl substituted products 6a–e were also obtained during the synthesis.
In the selective deacetylation step, we found that using potassium carbonate
or ammonia as base failed to give satisfactory results, with both low regio-
selectivity and low yield.[5,10] A more bulky base t-butyl amine was chosen
instead of potassium carbonate or ammonia as base to effectively regioselective
deacetylate 2-substituted-1,4-naphth-diyl diacetate. To achieve better regio-
selectivity, the reaction was carried out at low temperature (58C). With our
Scheme 1. Synthesis of Mansonone F analogues of 5a–e and 6a–e.

2670
S.-L. Huang et al.
modification, the deacetylation demonstrated high regioselectivity, giving
monoacetate 2 in much higher yields (75–92%). During the reaction, a small
amount of diphenol compounds were produced, which could finally be
oxidized to 2-methyl naphthoquinone and easily be washed off with CCl4.
Also the reaction time was significantly reduced from 4 days to about 5 h.[5]
The intermediates 3 and 4 were also obtained in high yields (overall yield
of 55–75% for three steps from 2 to 4). All of the crude intermediates
produced in this way could be used in the next step reaction without special
purification. The compound 4 was then treated with Lewis acid–mediated
debenzylation, cyclization, and oxidation to produce target compounds
5a–e and 6a–e in 7–39% overall yield.
The structure of prepared compounds 5a–e and 6a–e were determined
1
with fast atom bombardment-mass spectrometry (FAB-MS) and H NMR
analysis. The FAB-MS showed that the [M þ 1]þ peak of compounds 6 is
91 (m/z) more than the corresponding compounds 5, and the 1H NMR
showed extra proton signals at d 7.15–7.18 (2H, d), 7.23–7.24 (1H, t),
7.30–7.32 (2H, t), and 4.04–4.07 (2H, s), respectively. All these results
indicated the presence of a benzyl group in compounds 6. Comparing with
compounds 5, the aromatic proton signal in the 5-position at d 7.58–7.65
(1H, t) disappeared, and the aromatic protons in 4- and 6-positions gave
very simple signals. For example, the signals at d 7.57 (dd, 1H, J ¼ 7.0,
2.5 Hz), 8.05 (dd, 1H, J ¼ 7.0, 2.5 Hz) in 5a shifted to d 7.34 (d, 1H,
1
J ¼ 2.0 Hz), 7.90 (d, 1H, J ¼ 2.0 Hz) in 6a. The H-1H correlated spec-
troscopy (COSY) spectra showed no correlation between H-4 and H-5 and
no correlation between H-6 and H-5. Furthermore, the benzyl proton signal
(PhCH2) showed long-range correlations with C-4 and C-6, and 4,6-position
protons also showed long-range correlations with the carbon of PhCH2 in
the heteronuclear multiple-bond correlation (HMBC) experiment. All of the
observations strongly indicated that the benzyl group was located in the
5-position of the ring system.
There were four major products in the reaction of cyclization and deben-
zylation. The structure of these products were assigned as I, II, III, and IV
(Scheme 2). Compounds I and II were difficult to purify because of their extra-
ordinary phenolic hydroxyl group instability toward oxygen, but their struc-
tures could be determined by indirect ways. When compound I was
methylated by (CH3)2SO4/K2CO3/acetone, only one product V appeared.
Based on the structure of V, we could confirm the structure of compound I.
Structure of II was also proved the same way. Oxidation of III and IV by
SeO2 or air gave corresponding p-quinone VII and p-quinone VIII respect-
1
ively. Based on the H NMR spectra of III, IV, VII, and VIII, combined
with the oxidation mechanisms of phenoloid, it was easy to confirm the struc-
tures of III, IV, VII, and VIII. Clearly formation of compound I and III was
involved in a electrophilic substitution of benzyl cation generated and
attracted to the nucleophilic ortho-position of phenol during the Lewis
acid–mediated debenzylation of 4.[11–13]

9-Substituted Benzo[de]chromene-7,8-dione
2671
Scheme 2. Products of cyclization, debenzylation, and oxidation reactions of com-
pound 4a. Reagents and conditions: a, HBF4/ether, 58C, 5 min; b, (CH3)2SO4/
acetone/K2CO3, rt, 2 h; c, SeO2 or air, rt; d, SeO2, rt.
It was interesting that two products 5a (39%) and 6a (12%) were obtained
when compound I was oxidized by SeO2. The possible mechanism is proposed
as shown in Scheme 3. It is reasonable that the phenol group of compound I
could form the intermediate IX of organoselenium acid ester with SeO2.[14,15]
The intermediate IX was easy to transfer to the intermediate X by a [2,3]sig-
matropic rearrangement.[14,15] Because the benzyl group was a very good
leaving group, the benzyl cation was generated simultaneously when the
oxygen–selenium bond of X split to form o-quinone 5a. The benzyl cation
then electrophilicly attacked the nucleophilic 5-position of 5a by withdrawing
the electron effect of 7,8-dione to give corresponding compound 6a.
The series of analogues of 9-substitued benzo[de]chromene-7,8-dione
5b–e and 5-benzyl-9-substitued benzo[de]chromene-7,8-dione 6b–e were
prepared through a similar way.
When HBF4 was replaced by PPA (polyphosphoric acid) or TFA
(trifluoroacetic acid), the reactions failed to give satisfactory cyclization
products, and instead compound III and IV were formed as the major
products. It was clear that PPA and TFA were strong acids and good
reagents for debenzylation,[16] but their capability to catalyze the cyclization
was insufficient in this reaction.
The in vitro cytotoxicity of Mansonone F (isolated from Helicteres
angustifolia Linn), benzo[de]chromene-7,8-dione (prepared according to
literature[4]), 9-substituted benzo[de]chromene-7,8-dione compounds 5a–e,
and 5-benzyl-9-substitued benzo[de]chromene-7,8-dione 6a, 6d, 6e was
evaluated. The growth inhibition effect was assayed using the methyl
thiazolyl tetrazolium (MTT) method.[17] The concentration of tested
compounds for 50% inhibition (IC50) on human nasopharyngeal carcinoma
cell line (CNE2), the human lung adenocarcinoma cell line (GLC-82), and

2672
S.-L. Huang et al.
Scheme 3. Mechanism of oxidation of compound 4a by selenium dioxide.
Table 1. IC50 of Mansonone F and synthetic Mansonone analogous against human
cancer cell line
Human cancer cell
and IC50 (mM)
Compound
R
CNE2
Glc-82
A549
10-Hydroxycamptothecina
Mansonone F
Benzo[de]chromene-7,8-dione
—
—
1.04
27.34
5.23
0.23
15.53
4.76
3.71
15.94
8.58
H
-CH3
5a
5b
5c
5d
5e
6a
6d
6e
14.90
7.20
21.75
7.87
17.15
14.40
16.99
7.51
-CH2CH3
-CH(CH3)2
-CH2Ph
14.11
12.40
10.72
12.61
22.10
27.54
23.04
10.02
24.55
13.98
24.63
29.74
-CH2Ph-2-Cl
-CH3
-CH2Ph
25.27
15.78
—
-CH2Ph-2-Cl
—
a10-Hydroxycamptothecin was used as control.

9-Substituted Benzo[de]chromene-7,8-dione
2673
human lung adenocarcinoma cell line (A549) were determined, and the results
are summarized in Table 1.
From these assay data, the cytotoxicity of prepared compounds 5 and 6
was similar to that of natural product Mansonone F, indicating that the split
6-methyl or introduction of 5-benzyl and 9-substituted group would not
significantly effect the cytotoxicity.
CONCLUSION
In conclusion, we described a method for the synthesis of 6-demethyl-
Mansonone analogues of 5a–e and 6a–e. A novel regioselective deacetyla-
tion of 2-substituted-1,4-naphthdiyl diacetate was developed, resulting in
obtaining the monoacetate in high yield. The mechanisms of formation of
5a–e and 6a–e involving cyclization, debenzylation, and oxidation were
discussed. The cytotoxicity of the prepared compounds 5 and 6 were compar-
able with naturally occurring Mansonone F. The results would provide us
some useful information for future structural modification.
EXPERIMENTAL
Melting points were measured on a WRR melting-point apparatus (Shanghai
Physical Optical Equipment Manufacturer) or SGW X-4 melting-point
apparatus with microscope (Shanghai Physical Optical Equipment Manu-
1
facturer), and the thermometer was uncorrected. H NMR and 13C NMR
were recorded on a Varian Inova 500NB or Mercury-Plus 300 NMR instru-
ment with TMS as internal reference. Mass spectra were recorded on a VG
ZAB-HS and Finnigan TSQ Quantum instrument. IR spectra were recorded
on Bruker Equinox 55 Fourier transform spectrometer. Elemental analyses
were performed by Elementar Vario EL instrument. Silica H (60) was
purchased from Qingdao Marine Chemical Manufacturer.
Procedure for the Synthesis of Compound 2
1-Hydroxy-3-methylnaphthalen-4-yl Acetate (2a)
Vitamin K4 (7.8 g, 30 mmol) was dissolved in 120 mL of methanol with
stirring, and nitrogen was applied to maintain an inert atmosphere. To this
solution was added 2.2 g (30 mmol) t-butyl amine and the solution was
stirred for 30 min at room temperature. The solution was cooled to 58C and
stirred at this temperature for 5 h, and 3 mL of acetic acid was added to
quench the reaction. The reaction mixture was concentrated in vacuo, and
ice water was added to the solution to give deep brown oil, which was
rapidly solidified. The solid was collected through filtration and redissolved

2674
S.-L. Huang et al.
in 100 mL of chloroform. The organic phase was washed with water
(30 mL ꢀ 2) and dried with anhydrous sodium sulfate. Removal of the
solvent gave brown ropey gum, which could be easily solidified. Washing
the solid with CCl4 gave 6.0 g of 2 as yellow solid, yield 92%. The
compound was pure enough for the next step of the reaction. For analytical
purposes, the compound could be purified by crystallization from methanol:
1
mp 124.5–125.88C (lit.[18] mp 124–1258C). H NMR (300 MHz, CDCl3, d,
ppm) 2.08 (3H, s), 2.45 (3H, s), 6.13 (1H, s), 6.25 (1H, b), 7.30 (1H, t,
J ¼ 7 Hz), 7.42 (1H, t, J ¼ 7 Hz), 7.57 (1H, d, J ¼ 8 Hz), 7.88 (1H, d,
J ¼ 8 Hz). 13C NMR (75 MHz, CDCl3, d) 16.7, 21.1, 111.3, 120.4, 122.5,
124.2, 124.8, 126.7, 127.2, 127.6, 137.5, 149.7, 171.2. IR nmax (KBr)/
cm21: 3350, 3069, 2924, 1718, 1600, 1580, 1520, 1478, 1449, 1368, 1246,
1159, 1079. FAB-MS m/z 217 [M þ 1]þ. Anal. calcd. for C13H12O3: C,
72.21%; H, 5.59%. Found: C, 72.05%; H, 5.52%.
1-Hydroxy-3-ethylnaphthalen-4-yl Acetate (2b)
The compound was prepared from 2-ethyl-1,4-naphthoquinone according to
1
the procedure for 2a. Yield 85%. White solid, mp 138.5–139.68C. H NMR
(300 MHz, CDCl3, d, ppm) 1.18 (3H, t, J ¼ 8 Hz), 2.48 (3H, s), 2.53 (2H,
q, J ¼ 8 Hz), 5.61 (1H, b), 6.46 (1H, s), 7.40 (1H, t, J ¼ 7 Hz), 7.46 (1H, t,
J ¼ 7 Hz), 7.61 (1H, d, J ¼ 8 Hz), 7.97 (1H, d, J ¼ 8 Hz). 13C NMR
(75 MHz, CDCl3, d, ppm) 14.1, 20.7, 23.4, 109.3, 120.3, 122, 123.7, 124.5,
126.8, 127.3, 132, 136.6, 149.5, 170.8. IR nmax (KBr)/cm21: 3428, 3065,
2967, 2929, 1727, 1600, 1579, 1517, 1449, 1402, 1369, 1231, 1155, 859,
763, 742. ESI-MS m/z 229 [M 2 1]2. Anal. calcd. for C14H14O3: C,
73.03%; H, 6.13%. Found: C, 73.25%; H, 6.05%.
1-Hydroxy-3-isopropylnaphthalen-4-yl Acetate (2c)
The compound was prepared from 2-isopropyl-1,4-naphthoquinone according
1
to the procedure for 2a. Yield 84%. White solid, mp 92.1–94.38C. H NMR
(300 MHz, CDCl3, d, ppm) 1.21 (6H, d, J ¼ 7 Hz), 2.52 (3H, s), 3.12 (1H, q,
J ¼ 7), 6.08 (1H, b), 6.65 (1H, s), 7.39 (1H, t, J ¼ 8 Hz), 7.49 (1H, t,
J ¼ 8 Hz), 7.64 (1H, d, J ¼ 8 Hz), 8.05 (1H, d, J ¼ 8 Hz). 13C NMR
(75 MHz, CDCl3, d, ppm) 20.7, 22.8, 22.9, 27.5, 106.3, 120.7, 121.9, 123.6,
124.7, 126.8, 127.4, 135.9, 136.3, 149.8, 170.6. IR nmax (KBr)/cm21: 3454,
3059, 2963, 1732, 1600, 1580, 1517, 1457, 1399, 1370, 1231, 1065, 771,
741. ESI-MS m/z 243 [M 2 1]2. Anal. calcd. for C15H16O3: C, 73.75%; H,
6.60%. Found: C, 73.46%; H, 6.59%.
1-Hydroxy-3-phenylnaphthalen-4-yl Acetate (2d)
The compound was prepared from 2-phenylpropyl-1,4-naphthoquinone
according to the procedure for 2a. Yield 75%. White solid, mp

9-Substituted Benzo[de]chromene-7,8-dione
2675
127.5–128.98C. 1H NMR (300 MHz, CDCl3, d, ppm) 2.37 (3H, s), 3.81 (2H,
s), 5.87 ( 1H, b), 6.24 (1H, s), 7.07 (2H, d, J ¼ 7 Hz), 7.13 (1H, t, J ¼ 7 Hz),
7.19 (2H, t, J ¼ 7 Hz), 7.33 (1H, t, J ¼ 8 Hz), 7.44 (1H, t, J ¼ 8 Hz), 7.60
(1H, d, J ¼ 8 Hz), 7.96 (1H, d, J ¼ 8 Hz). 13C NMR (75 MHz, CDCl3, d,
ppm) 21.1, 36.6, 110.4, 121, 122.5, 124.4, 125.2, 126.5, 127.3, 127.8,
128.7, 129.2, 129.6, 137.5, 139.8, 150, 170.7. IR nmax (KBr)/cm-1: 3409,
3026, 2922, 1726, 1606, 1495, 1456, 1370, 1234, 1171, 1074, 935, 874,
757, 734, 705. ESI-MS m/z 291 [M 2 1]2. Anal. calcd. for C19H16O3: C,
78.06%; H, 5.52%. Found: C, 78.06%; H, 5.82%.
1-Hydroxy-3-(2-chlorophenyl)naphthalen-4-yl Acetate (2e)
The compound was prepared from 2-(2-chlorophenyl)-1,4-naphthoquinone
according to the procedure for 2a. Yield 78%, white solid, mp 136.2–
1
137.98C. H NMR (300 MHz, CDCl3, d, ppm) 2.45 (3H, s), 4.04 (2H, s),
5.55 (1H, b), 6.37 (1H, s), 7.06 (2H, d, J ¼ 7 Hz), 7.13 (1H, t, J ¼ 7 Hz),
7.16 (1H, t, J ¼ 7 Hz), 7.38 (1H, d, J ¼ 7 Hz), 7.44 (1H, t, J ¼ 8 Hz), 7.52
(1H, t, J ¼ 8 Hz), 7.66 (1H, d, J ¼ 8 Hz), 8.06 (1H, d, J ¼ 8 Hz). 13C NMR
(75 MHz, CDCl3, d, ppm) 21.1, 33.8, 110.2, 121, 122.5, 124.5, 125.3, 127,
127.3, 127.8, 128, 128.2, 129.5, 131.1, 134.2, 137.4, 137.8, 150, 170.8 . IR
nmax (KBr)/cm21: 3449, 1719, 1600, 1580, 1518, 1471, 1439, 1397, 1371,
1236, 1154, 1073, 857, 759. ESI-MS m/z 325 [M 2 1]2. Anal. calcd. for
C19H15ClO3: C, 69.84%; H, 4.63%. Found: C, 69.81%; H, 4.90%.
Procedure for the Synthesis of Compound 3
1-(Benzyloxy)-3-methylnaphthalen-4-yl Acetate (3a)
To a solution of 4.32 g (20 mmol) 2a in 100 mL of acetone was added 3.76 g
(22 mmol) benzyl bromine and 11 g (80 mmol) of grinded anhydrous
potassium carbonate. Nitrogen was applied to maintain an inert atmosphere.
The reaction mixture was stirred for 5 h at room temperature and was concen-
trated in vacuo. The solid was separated by filtration and was thoroughly
washed with acetone. The filtrate was concentrated to give a yellow brown
solid. Washing with hexane gave a yellow solid (5.81 g, 95% yield). The
compound was pure enough for the next step of the reaction. For analytical
purposes, the compound could be recrystallized in methanol: mp 103.8–
104.98C. (lit.[19] mp 105–1078C). 1H NMR (300 MHz, CDCl3, d, ppm)
2.30 (3H, s), 2.46 (3H, s), 5.21 (2H, s), 6.72 (1H, s), 7.34 (1H, tt, J ¼ 7,
1.5 Hz), 7.38–7.52 (6H, m), 7.66 (1H, d, J ¼ 8 Hz), 8.27 (1H, d, J ¼ 8 Hz).
13C NMR (75 MHz, CDCl3, d, ppm) 17.3, 21.0, 70.7, 107.9, 120.7, 122.8,
125.2, 125.4, 126.4, 127.4, 127.7, 128.0, 128.2, 128.8, 137.2, 138.1, 152.5,
169.6. IR nmax (KBr)/cm21: 3034, 2923, 2873, 1761, 1635, 1600, 1584,
1505, 1455, 1360, 1199, 1156, 1110, 1085, 773, 749, 698. FAB-MS m/z

2676
S.-L. Huang et al.
306 [Mþ]. Anal. calcd. for C20H18O3: C, 78.41%; H, 5.92%. Found: C,
78.63%; H, 5.96%.
1-(Benzyloxy)-3-ethylnaphthalen-4-yl Acetate (3b)
The compound was prepared from 2b according to the procedure for 3a. Yield
94%. White solid, mp 85.8–86.88C. 1H NMR (500 MHz, CDCl3, d, ppm) 1.24
(3H, t, J ¼ 8 Hz), 2.45 (3H, s), 2.64 (2H, q, J ¼ 8 Hz), 5.22 (2H, s), 6.76 (1H,
s), 7.34 (1H, tt, J ¼ 7, 1.5 Hz), 7.41 (2H, tt, J ¼ 7, 1.5 Hz), 7.42 (1H, td, J ¼ 8,
1.5 Hz), 7.49 (1H, td, J ¼ 8, 1.5 Hz), 7.52 (2H, d, J ¼ 7 Hz), 7.65 (1H, dd,
J ¼ 8, 1.5 Hz), 8.29 (1H, dd, J ¼ 8, 1.5 Hz). 13C NMR (75 MHz, CDCl3, d,
ppm) 14.4, 20.6, 23.9, 70.2, 105.9, 120.5, 122.3, 124.7, 125, 126.9,
127.3(2c), 127.6, 127.8, 128.4(2c), 131.7, 136.8, 137, 152.4, 169.5. IR nmax
(KBr)/cm21: 3034, 2969, 2934, 1759, 1599, 1506, 1458, 1369, 1207, 1159,
771, 752, 698. ESI-MS m/z 343 [M þ Na]þ. Anal. calcd. for C21H20O3: C,
78.73%; H, 6.29%; Found: C, 78.99%; H, 6.46%.
1-(Benzyloxy)-3-isopropylnaphthalen-4-yl Acetate (3c)
The compound was prepared from 2c according to the procedure for 3a. Yield
94%. White solid, mp 89.2–89.58C. 1H NMR (500 MHz, CDCl3, d, ppm) 1.26
(6H, d), 2.47 (3H, s), 3.17 (1H, d, J ¼ 7 Hz), 5.24 (2H, s), 6.81 (1H, s), 7.35
(1H, tt, J ¼ 7, 1.5 Hz), 7.42 (2H, tt, J ¼ 7, 1.5 Hz), 7.43 (1H, td, J ¼ 8,
1.5 Hz), 7.50 (1H, td, J ¼ 8, 1.5 Hz), 7.53 (2H, d, J ¼ 7 Hz), 7.65 (1H, dd,
J ¼ 8, 1.5 Hz), 8.29 (1H, dd, J ¼ 8, 1.5 Hz). 13C NMR (75 MHz, CDCl3, d,
ppm) 20.7, 23, 23, 27.8, 70.3, 102.9, 120.7, 122.3, 124.9, 124.9, 127, 127.4,
127.6, 127.8, 128.4, 136, 136.1, 136.9, 152.7, 169.6. IR nmax (KBr)/cm21
:
3068, 2960, 2871, 1762, 1599, 1507, 1464, 1365, 1199, 1156, 1075, 770,
740, 694. ESI-MS m/z 357 [M þ Na]þ. Anal. calcd. for C22H22O3: C,
79.02%; H, 6.63%. Found: C, 79.30%; H, 6.78%.
1-(Benzyloxy)-3-phenylnaphthalen-4-yl Acetate (3d)
The compound was prepared from 2d according to the procedure for 3a. Yield
98%. White solid, mp 88.8–89.38C. 1H NMR (500 MHz, CDCl3, d, ppm) 2.41
(3H, s), 4.00 (2H, s), 5.11 (2H, s), 6.63 (1H, s), 7.18 (2H, d, J ¼ 7 Hz), 7.21
(1H, tt, J ¼ 7, 1.5 Hz), 7.28 (2H, t, J ¼ 7 Hz), 7.33 (1H, tt, J ¼ 7, 1.5 Hz),
7.37 (2H, t, J ¼ 7 Hz), 7.43 (2H, d, J ¼ 7 Hz), 7.45 (1H, td, J ¼ 8, 1 Hz),
7.51 (1H, td, J ¼ 8, 1 Hz), 7.68 (1H, dd, J ¼ 8, 1 Hz), 8.29 (1H, dd, J ¼ 8,
1 Hz). 13C NMR (75 MHz, CDCl3, d, ppm) 20.6, 36.6, 70.2, 106.9, 120.7,
122.4, 125.1, 125.3, 126.1, 127.1, 127.3, 127.6, 127.8, 128.4(4c), 128.8,
128.8(2c), 136.6, 137.7, 139.5, 152.3, 169.4. IR nmax (KBr)/cm21: 3025,
2947, 1753, 1602, 1494, 1455, 1368, 1207, 1157, 1116, 1082, 897, 847,
770, 732, 698. ESI-MS m/z 405 [M þ Na]þ. Anal. calcd. for C26H22O3: C,
81.65%; H, 5.80%. Found: C, 81.88%; H, 5.89%.

9-Substituted Benzo[de]chromene-7,8-dione
2677
1-(Benzyloxy)-3-(2-chlorophenyl)naphthalen-4-yl Acetate (3e)
This compound was prepared from 2e according to the procedure for 3a. Yield
1
96%. White solid, mp 116.4–117.58C. H NMR (500 MHz, CDCl3, d, ppm)
2.40 (3H, s), 4.11 (2H, s), 5.10 (2H, s), 6.59 (1H, s), 7.06 (1H, dd, J ¼ 7,
1.5 Hz), 7.12 (1H, td, J ¼ 7, 1.5 Hz), 7.15 (1H, td, J ¼ 7, 1.5 Hz), 7.33 (1H,
tt, J ¼ 7, 1.5 Hz), 7.35 (2H, tt, J ¼ 7, 1.5 Hz), 7.37 (1H, td, J ¼ 8, 1.5 Hz),
7.41 (2H, dd, J ¼ 7, 1.5 Hz), 7.45 (1H, td, J ¼ 8, 1.5 Hz), 7.51 (1H, td,
J ¼ 8, 1.5 Hz), 7.67 (1H, dd, J ¼ 8, 1.5 Hz), 8.30 (1H, dd, J ¼ 8, 1.5 Hz).
13C NMR (75 MHz, CDCl3, d, ppm) 20.6, 33.8, 70.2, 106.7, 120.7, 122.4,
125.2, 125.4, 126.7, 127.1, 127.2(2C), 127.5, 127.6, 127.7, 128.3(3C),
129.2, 130.7, 133.9, 136.5, 137.1, 137.9, 152.3, 169.3. IR nmax (KBr)/
cm21: 3065, 3032, 2941, 1753, 1602, 1447, 1369, 1213, 1156, 1081, 920,
856, 760, 740, 698. ESI-MS m/z 439 [M þ Na]þ. Anal. calcd. for
C26H21ClO3: C, 74.91%; H, 5.08%. Found: C, 74.92%; H, 5.22%.
Procedure for the Synthesis of Compound 4
1-(1-(Benzyloxy)-3-methylnaphthalen-4-yloxy)propan-2-one (4a)
Sodium hyposulphite (7 g, 40 mmol) and 3.2 g (80 mmol) of sodium
hydroxide were added to a solution of 6.12 g (20 mmol) 3a in 120 mL of
methanol/water (2 : 1). The reaction mixture was refluxed for 1 h with
stirring and was concentrated in vacuo. Ice water (100 mL) was added, and
the pH value was adjusted to 4–5 with 5% hydrochloric acid. The thus-
formed pink solid was collected through vacuum filtration and was re-
dissolved in ether. The organic phase was washed with water (30 ml ꢀ 2)
and was dried with anhydrous sodium sulfate. Removal of the solvent gave
4.85 g of brown solid, which was pure enough for the next step of the
reaction without further purification.
To a solution of this solid (4.85 g, 18.4 mmol) in 100 mL of actone, 2.04 g
(22 mmol) chloroacetone, 7.62 g (55 mmol) grinded anhydrous potassium
carbonate, and 0.25 g potassium iodide were added. Nitrogen was applied to
maintain an inert atmosphere, and the reaction mixture was stirred for 5 h at
room temperature. The solvent was then removed in vacuo, and 100 mL of
water was added. The mixture was extracted with ether (30 mL ꢀ 3),
washed with water (30 mL ꢀ 2), and dried with anhydrous sodium sulfate.
Removal of the solvent gave brown solid. Washing the solid with methanol
gave 4.6 g (two steps, 72% yield) of 4a as yellowish brown solid. The
compound could be used directly in the next step without purification. For
analytical purposes, the sample could be recrystallized from methanol: mp
1
102.6–104.98C. H NMR (300 MHz, CDCl3, d, ppm) 2.39 (3H, s), 2.42
(3H, s), 4.49 (2H, s), 5.19 (2H, s), 6.67 (1H, s), 7.33 (1H, tt, J ¼ 7, 1.5 Hz),
7.38–7.44 (3H, m), 7.47–7.52 (3H, m), 7.93 (1H, d, J ¼ 8 Hz), 8.26 (1H,

2678
S.-L. Huang et al.
d, J ¼ 7 Hz). 13C NMR (75 MHz, CDCl3, d, ppm) 16.6, 26.7, 70.2, 78.0,
107.9, 120.9, 122.5, 124.7, 125.3, 125.5, 126.8, 127.2, 127.8(2C), 128.2,
128.4(2C), 136.9, 144.9, 151.0, 204.8. IR nmax (KBr)/cm-1: 3056, 2917,
2873, 1740, 1632, 1598, 1493, 1460, 1398, 1376, 1354, 1266, 1233, 1091,
1064, 764, 708. FAB-MS m/z 320 [Mþ, 10], 229 [Mþ-PhCH2, 20], 91
[PhCHþ2 , 100]. Anal. calcd. for C21H20O3: C, 78.73%; H, 6.29%. Found: C,
78.76%; H, 6.32%.
1-(1-(Benzyloxy)-3-ethylnaphthalen-4-yloxy)propan-2-one (4b)
The compound was prepared from 3b according to the procedure for 4a. Yield
59%. White solid, mp 77.6–78.38C. 1H NMR (500 MHz, CDCl3, d, ppm) 1.29
(3H, t, J ¼ 7.5 Hz), 2.40 (3H, s), 2.81 (2H, q, J ¼ 7.5 Hz), 4.51 (2H, s), 5.22
(2H, s), 6.73 (1H, s), 7.36 (1H, tt, J ¼ 7, 1.5), 7.42 (2H, t, J ¼ 7 Hz), 7.44 (1H,
td, J ¼ 8, 1.5 Hz), 7.51 (1H, td, J ¼ 8, 1.5 Hz), 7.53 (2H, d, J ¼ 7 Hz), 7.95
(1H, d, J ¼ 8 Hz), 8.29 (1H, d, J ¼ 8 Hz). 13C NMR (75 MHz, CDCl3, d,
ppm) d 15.2, 23.2, 26.7, 70.3, 78.8, 106.4, 121, 122.4, 124.8, 125.4, 126.7,
127.3, 127.8, 128.2, 128.4, 131.8, 136.9, 144.3, 151.2, 204.8. IR nmax
(KBr)/cm21: 3068, 2970, 2874, 1725, 1595, 1502, 1461, 1375, 1265, 1234,
1161, 1097, 983, 838, 759, 700. ESI-MS m/z 357 [M þ Na]þ. Anal. calcd.
for C22H22O3: C, 79.02%; H, 6.63%. Found: C, 78.83%; H, 6.71%.
1-(1-(Benzyloxy)-3-isopropylnaphthalen-4-yloxy)propan-2-one (4c)
The compound was prepared from 3c according to the procedure for 4a. Yield
1
71%. White solid, mp 111.0–111.98C. H NMR (500 MHz, CDCl3, d, ppm)
1.27 (6H, d, J ¼ 7.5 Hz), 2.39 (3H, s), 3.52 (1H, sept, J ¼ 7 Hz), 4. 49 (2H,
s), 5.23 (2H, s), 6.76 (1H, s), 7.35 (1H, t, J ¼ 7 Hz), 7.40 (2H, t, J ¼ 7 Hz),
7.42 (1H, t, J ¼ 8 Hz), 7.50 (1H, t, J ¼ 8 Hz), 7.52 (2H, d, J ¼ 7 Hz), 7.93
(1H, d, J ¼ 8 Hz), 8.28 (1H, d, J ¼ 8 Hz). 13C NMR (75 MHz, CDCl3, d,
ppm) 23.6, 26.6, 26.7, 70.3, 79.1, 103.3, 121.2, 122.4, 124.8, 125.3, 126.7,
127.3, 127.8, 128.1, 128.4, 136.2, 136.9, 143.3, 151.5, 204.7. IR nmax
(KBr)/cm21: 3072, 2964, 2932, 2874, 1738, 1597, 1504, 1457, 1394, 1372,
1234, 1158, 1091, 980, 842, 765, 703. ESI-MS m/z 371 [M þ Na]þ. Anal.
calcd. for C23H24O3: C, 79.28%; H, 6.94%. Found: C, 79.07%; H, 6.98%.
1-(1-(Benzyloxy)-3-phenylnaphthalen-4-yloxy)propan-2-one (4d)
The compound was prepared from 3d according to the procedure for 4a. Yield
65%. White solid, mp 83.1–84.68C. 1H NMR (500 MHz, CDCl3, d, ppm) 2.25
(3H, s), 4.16 (2H, s), 4.37 (2H, s), 5.13 (2H, s), 6.64 (1H, s), 7.16–7.20 (3H,
m), 7.26 (2H, tt, J ¼ 7, 1 Hz), 7.33 (1H, tt, J ¼ 7, 1 Hz), 7.38 (2H, tt, J ¼ 7,
1 Hz), 7.44–7.47 (3H, m), 7.52 (1H, td, J ¼ 8, 1 Hz), 7.95 (1H, dd, J ¼ 8,
1 Hz), 8.31 (1H, dd, J ¼ 8, 1 Hz). 13C NMR (75 MHz, CDCl3, d, ppm)
26.5, 36.1, 70.2, 78.6, 107.6, 121.1, 122.5, 125.1, 125.7, 126, 126.8,

9-Substituted Benzo[de]chromene-7,8-dione
2679
127.3(2C), 127.7, 128.2, 128.4(3C), 128.5, 128.6(2C), 136.7, 140.3, 145.1,
151, 204.3. IR nmax (KBr)/cm21: 3063, 3032, 2917, 2874, 1724, 1596,
1496, 1455, 1359, 1232, 1155, 1093, 980, 847, 763, 706. ESI-MS m/z 419
[M þ Na]þ. Anal. calcd. for C27H24O3: C, 81.79%; H, 6.10%. Found: C,
82.05%; H, 6.16%.
1-(1-(Benzyloxy)-3-(2-chlorophenyl)naphthalen-4-yloxy)
propan-2-one (4e)
The compound was prepared from 3e according to the procedure for 4a. Yield
1
78%. White solid, mp 99.7–100.38C. H NMR (500 MHz, CDCl3, d, ppm)
2.31 (3H, s), 4.26 (2H, s), 4.45 (2H, s), 5.11 (2H, s), 6.57 (1H, s), 7.03 (1H,
dd, J ¼ 7, 2 Hz), 7.12 (1H, td, J ¼ 7, 1.5 Hz), 7.17 (1H, td, J ¼ 7, 2 Hz),
7.32 (1H, tt, J ¼ 7, 1 Hz), 7.36 (2H, tt, J ¼ 7, 1.5 Hz), 7.39 (1H, dd, J ¼ 7,
1.5 Hz), 7.43 (2H, d, J ¼ 7 Hz), 7.47 (1H, td, J ¼ 8, 1 Hz), 7.54 (1H, td,
J ¼ 8, 1 Hz), 7.96 (1H, dd, J ¼ 8, 1 Hz), 8.31 (1H, dd, J ¼ 8, 1 Hz). 13C
NMR (75 MHz, CDCl3, d, ppm) 26.6, 33.5, 70.2, 78.5, 107.2, 121.2, 122.6,
125.2, 125.9, 126.8, 126.9, 127.2, 127.3(2C), 127.5, 127.7, 128.2,
128.4(2C), 129.3, 130.5, 134, 136.7, 137.8, 145.2, 151.1, 204.5. IR nmax
(KBr)/cm21: 3061, 2935, 2910, 2881, 1734, 1594, 1503, 1465, 1391, 1359,
1264, 1231, 1183, 1157, 1089, 980, 847, 755, 703. ESI-MS m/z 453
[M þ Na]þ. Anal. calcd. for C27H23ClO3: C, 75.25%; H, 5.38%. Found: C,
75.45%; H, 5.50%.
Procedure for the Synthesis of Compounds 5 and 6
3,9-Dimethylbenzo[de]chromene-7,8-dione (5a) and 5-Benzyl-3,
9-dimethylbenzo[de]chromene-7,8-dione (6a)
Compound 4a (4 g, 12.5 mmol) was dissolved in 40 mL of dichloromethane,
and the mixture was cooled to 58C. To this solution, 18 mL of ice-cooled tetra-
fluoroboric acid/ether solution (anhydrous, 58% HBF4 in ether) were added
under vigorous stirring. After 5 min, 50 mL of water were added and the
organic layer was separated. The aqueous layer was extracted with dichloro-
methane (30 mL ꢀ 2). The organic layer was combined, washed with water
(30 mL ꢀ 2), and dried with anhydrous sodium sulfate. The solution was con-
centrated, and the residue was redissolved in 80 mL of chloroform. Selenium
dioxide (8.2 g, 75 mmol) was added, and the solution was stirred overnight at
room temperature. The solid was removed, and the organic solution was con-
centrated to give 4.5 g of a purple solid. The crude product was purified by
chromatography (chloroform/methanol 5 : 1) to give a purple-black solid as
the final product 5a[20] (1.10 g, 39% yield). Mp 205–2078C. 1H NMR
(500 MHz, CDCl3, d, ppm) 1.97 (3H, s), 2.11 (3H, d, J ¼ 1.5 Hz), 7.06
(1H, q, J ¼ 1.5 Hz), 7.57 (1H, dd, J ¼ 7, 2.5 Hz), 7.58 (1H, t, J ¼ 7 Hz),

2680
S.-L. Huang et al.
8.05 (1H, dd, J ¼ 7, 2.5 Hz). 13C NMR (125 MHz, CDCl3, d, ppm) 8.1, 13.4,
112.6, 114.1, 127.0, 128.9, 129.5, 130.9, 131.2, 132.4, 141.5, 161.8, 178.3,
179.7. IR nmax (KBr)/cm21: 3444, 2923, 1695, 1654, 1599, 1571, 1494,
1452, 1378, 1334, 1276, 1200, 1141, 758, 701. FAB-MS m/z 227
[M þ 1]þ. Anal. calcd. for C14H10O3: C, 74.33%; H, 4.46%. Found: C,
74.29%; H, 4.36%.
Compound 6a was also isolated from the reaction mixture: purple-black solid,
0.45 g, yield 12%. Mp 145–1478C. 1H NMR (500 MHz, CDCl3, d, ppm) 1.94
(3H, s), 2.04 (3H, d, J ¼ 1 Hz), 4.04 (2H, s), 7.02 (1H, q, J ¼ 1 Hz), 7.18 (2H,
dd, J ¼ 7, 1.5 Hz), 7.24 (1H, tt, J ¼ 7, 1.5 Hz), 7.31 (2H, td, J ¼ 7, 1.5 Hz),
7.34 (1H, d, J ¼ 2 Hz), 7.90 (1H, d, J ¼ 2 Hz). 13C NMR (125 MHz,
CDCl3, d, ppm) 7.5, 12.8, 41.9, 112.2, 113.1, 121.6, 126.9, 128.8(3C),
128.9(2C), 129.1, 131.2, 131.4, 138.8, 141.3, 146.2, 161.7, 178.1, 179.8. IR
nmax (KBr)/cm21: 2922, 1693, 1631, 1606, 1579, 1494, 1437, 1375, 1277,
1180, 846, 757, 710. FAB-MS m/z 317 [M þ 1]þ. Anal. calcd. for
C21H16O3: C, 79.73%; H, 5.10%. Found: C, 79.91%; H, 5.08%.
9-Ethyl-3-methylbenzo[de]chromene-7.8-dione (5b) and
5-Benzyl-9-ethyl-3-methylbenzo[de]chromene-7,8-dione (6b)
Compound 5b was prepared from 4b according to the procedure for 5a: yield
1
16%, purple-black solid. Mp 145–1478C. H NMR (500 MHz, CDCl3, d,
ppm) 1.08 (3H, t, J ¼ 7 Hz), 2.11 (3H, s), 2.51 (2H, q, J ¼ 7 Hz), 7.06 (1H,
s), 7.55 (1H, d, J ¼ 6 Hz), 7.58 (1H, t, J ¼ 7 Hz), 8.04 (1H, dd, J ¼ 6,
2.5 Hz). IR nmax (KBr)/cm21: 2971, 2931, 1693, 1626, 1597, 1574, 1457,
1365, 1334, 1278, 1196, 1169, 1140, 866, 785. FAB-MS m/z 241
[M þ 1]þ. Anal. calcd. for C15H12O3: C, 74.99%; H, 5.03%. Found: C,
75.21%; H, 4.85%.
Compound 6b was also isolated from the reaction mixture: yield 6%, purple-
black solid. Mp 106–1108C. 1H NMR (500 MHz, CDCl3, d, ppm) 1.05 (3H, t,
J ¼ 7 Hz), 2.05 (3H, s), 2.47 (2H, q, J ¼ 7 Hz), 4.03 (2H, s), 7.03 (1H, s), 7.17
(2H, d, J ¼ 7 Hz), 7.24 (1H, t, J ¼ 7 Hz), 7.31 (2H, t, J ¼ 7 Hz), 7.35 (1H, d,
J ¼ 1 Hz), 7.92 (1H, d, J ¼ 1 Hz). IR nmax (KBr) cm21: 3061, 3027, 2967,
1695, 1652, 1602, 1572, 1493, 1453, 1375, 1336, 1277, 1178, 1092, 765,
700. FAB-MS m/z 331 [M þ 1]þ. Anal. calcd. for C22H18O3: C, 79.98%;
H, 5.49%. Found: C, 80.23%; H, 5.38%.
9-Isopropyl-3-methylbenzo[de]chromene-7,8-dione (5c) and
5-Benzyl-9-isopropyl-3-methylbenzo[de]-chromene-7,8-dione (6c)
Compound 5c was prepared from 4c according to the procedure for 5a: yield
1
16%, purple-black solid. Mp 154–1578C. H NMR (500 MHz, CDCl3, d,
ppm) 1.26 (6H, d, J ¼ 7.0 Hz), 2.11 (3H, d, J ¼ 1.5 Hz), 3.38 (1H, d,

9-Substituted Benzo[de]chromene-7,8-dione
2681
J ¼ 7.0 Hz), 7.06 (1H, q, J ¼ 1.5 Hz), 7.57 (2H, m), 8.06 (1H, dd, J ¼ 6,
2.5 Hz). IR nmax (KBr) cm21: 3067, 2971, 2926, 1694, 1630, 1597, 1557,
1455, 1376, 1357, 1325, 1192, 1137, 885, 788, 753. FAB-MS m/z 255
[M þ 1]þ. Anal. calcd. for C16H14O3: C, 75.57%; H, 5.55%. Found: C,
75.49%; H, 5.34%.
Compound 6c was also isolated from the crude product: yield 7%, purple-
black solid. Mp 137–1408C. 1H NMR (500 MHz, CDCl3, d, ppm) 1.25
(6H, d, J ¼ 7 Hz), 2.06 (3H, s), 3.36 (1H, sept, J ¼ 7 Hz), 4.05 (2H, s),
7.04 (1H, s), 7.16 (2H, d, J ¼ 7 Hz), 7.24 (1H, t, J ¼ 7 Hz), 7.31 (2H, t,
J ¼ 7 Hz), 7.35 (1H, d, J ¼ 1.5 Hz), 7.92 (1H, d, J ¼ 1.5 Hz). IR nmax
(KBr) cm21: 3062, 3027, 2957, 1695, 1628, 1604, 1555, 1494, 1453, 1378,
1332, 1280, 1178, 1112, 1068, 754, 705. FAB-MS m/z 345 [M þ 1]þ. Anal.
calcd. for C23H20O3: C, 80.21%; H, 5.85%. Found: C, 80.05%; H, 5.88%.
9-Benzyl-3-methylbenzo[de]chromene-7,8-dione (5d) and
5,9-Dibenzyl-3-methylbenzo[de]chromene-7,8-dione (6d)
Compound 5d was prepared from 4d according to the procedure for 5a: yield
1
11%, purple-black solid. Mp 136–1398C. H NMR (500 MHz, CDCl3, d,
ppm) 2.11 (3H, d, J ¼ 1 Hz), 3.85 (2H, s), 7.09 (1H, q, J ¼ 1.5 Hz), 7.15
(1H, tt, J ¼ 7, 1.5 Hz), 7.23 (2H, t, J ¼ 7 Hz), 7.34 (2H, d, J ¼ 7 Hz), 7.56
(1H, dd, J ¼ 7, 1.5 Hz), 7.60 (1H, t, J ¼ 8 Hz), 8.06 (1H, dd, J ¼ 7,
1.5 Hz). IR nmax (KBr)/cm21: 1694, 1631, 1598, 1565, 1492, 1473, 1453,
1363, 1333, 1275, 1208, 1139, 758, 703. FAB-MS m/z 303 [M þ 1]þ. Anal.
calcd. for C20H14O3: C, 79.46%; H, 4.67%. Found: C, 79.69%; H, 4.55%.
Compound 6d was also isolated from the crude product: yield 8%, purple-
black solid. Mp 191–1948C. 1H NMR (500 MHz, CDCl3, d, ppm) 2.05
(3H, d, J ¼ 1.5 Hz), 3.83 (2H, s), 4.05 (2H, s), 7.07 (1H, q, J ¼ 1 Hz), 7.14
(1H, tt, J ¼ 6, 1.5 Hz), 7.15 (2H, d, J ¼ 6 Hz), 7.21 (2H, t, J ¼ 6 Hz),
7.23 (1H, tt, J ¼ 6, 1.5 Hz), 7.30 (2H, t, J ¼ 7 Hz), 7.33 (2H, d, J ¼ 7 Hz),
7.36 (1H, d, J ¼ 2 Hz), 7.94 (1H, d, J ¼ 1.5 Hz). IR nmax (KBr)/cm21
:
3026, 1697, 1629, 1605, 1574, 1493, 1452, 1362, 1335, 1278, 1242, 1169,
702. FAB-MS m/z 393 [M þ 1]þ. Anal. calcd. for C27H20O3: C, 82.63%;
H, 5.14%. Found: C, 82.85%; H, 5.13%.
9-(2-Chlorobenzyl)-3-methylbenzo[de]chromene-7,8-dione (5e) and
5-Benzyl-9-(2-chlorobenzyl)-3-methylbenzo[de]chromene-7,8-dione (6e)
Compound 5e was prepared from 4e according to the procedure for 5a: yield
7%, purple-black solid. Mp 197–1998C. 1H NMR (500 MHz, CDCl3, d, ppm)
d 2.11 (3H, d, J ¼ 1 Hz), 3.99 (2H, s), 7.05 (1H, q, J ¼ 1 Hz), 7.10 (2H, m),
7.23 (1H, dd, J ¼ 6, 3.5 Hz), 7.33 (1H, dd, J ¼ 6, 3 Hz), 7.61 (1H,
d, J ¼ 7 Hz), 7.65 (1H, t, J ¼ 8 Hz), 8.13 (1H, d, J ¼ 7 Hz). IR nmax

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S.-L. Huang et al.
(KBr)/cm21: 1696, 1630, 1598, 1565, 1472, 1439, 1362, 1335, 1272, 1207,
1161, 1139, 942, 853, 764. FAB-MS m/z 337 [M þ 1]þ. Anal. calcd. for
C20H13ClO3: C, 71.33%; H, 3.89%. Found: C, 71.12%; H, 3.95%.
Compound 6e was also isolated from the crude product: yield 3%, purple-
1
black solid. Mp 192–1958C. H NMR (500 MHz, CDCl3, d, ppm) d 2.05
(3H, d, J ¼ 1 Hz), 3.97 (2H, s), 4.07 (2H, s), 7.03 (1H, q, J ¼ 1 Hz), 7.08
(1H, t, J ¼ 6 Hz), 7.09 (1H, t, J ¼ 6 Hz), 7.18 (2H, d, J ¼ 7 Hz), 7.22 (1H,
dd, J ¼ 6, 3.5 Hz), 7.24 (1H, tt, J ¼ 7, 1.5 Hz), 7.32 (3H, m), 7.39 (1H, s),
7.98 (1H, s). IR nmax (KBr)/cm21: 1696, 1632, 1604, 1575, 1493, 1470,
1440, 1368, 1336, 1278, 1224, 1173, 753, 704. FAB-MS m/z 427
[M þ 1]þ. Anal. calcd. for C27H19ClO3: C, 75.97%; H, 4.49%. Found: C,
75.78%; H, 4.61%.
1-Methylbenzo[de]chromene-7,8-dione
Produced as in the literature[4]: purple-black solid. Mp 235–2378C. 1H NMR
(500 MHz, CDCl3, d, ppm) 2.15 (3H, d, J ¼ 1.5 Hz), 6.06 (1H, s), 7.06
(1H, q, J ¼ 1.5 Hz), 7.66 (1H, d, J ¼ 8 Hz), 7.72 (1H, t, J ¼ 8 Hz),
8.16 (1H, d, J ¼ 8 Hz). IR nmax (KBr)/cm21: 3087, 1696, 1622, 1601,
1569, 1555, 1473, 1369, 1279, 1205, 1133, 845, 771. ESI-MS m/z 213
[M þ 1]þ. Anal. calcd. for C13H8O3: C, 73.58%; H, 3.80%. Found: C,
73.81%; H, 3.75%.
8-Benzyl-7-methoxy-3,9-dimethylbenzo[de]chromene (V)
Compound I was prepared from 4a and subjected to flash chromatography
(silica, ethyl acetate–petroleum ether, 1 : 8) under N2, after concentration of
the appropriate fraction under vacuum at room temperature. A pale brown
solid was obtained. Immediately, compound II (320 mg, 1.05 mmol),
acetone (5 mL), dimethyl sulfate (400 mg, 3.15 mmol), and anhydrous
potassium carbonate (870 mg, 6.30 mmol) were stirred under N2 at room
temperature for 2 h. Compound II disappeared, and a new bright green dot
was observed by thin-layer chromatography (TLC) in UV365 (RF ¼ 0.29,
petroleum ether). Acetone was concentrated in vacuo. Water was added and
then extracted with CHCl3, and the product was washed once with H2O,
dried (Na2SO4), filtered, and evaporated in vacuo to yield a crude residue.
The residue was purified by flash chromatography (silica, petroleum ether)
1
to afford compound III (285 mg, yield 86%) as a white solid. H NMR
(300 MHz, CDCl3, d, ppm) 1.85 (3H, d, J ¼ 1 Hz), 2.06 (3H, s), 3.72 (3H,
s), 4.22 (2H, s), 6.66 (1H, d, J ¼ 8 Hz), 6.70 (1H, d, J ¼ 1 Hz), 7.08–7.22
(5H, m), 7.26 (1H, t, J ¼ 8 Hz), 7.56 (1H, d, J ¼ 8 Hz). ESI-MS m/z 317
[M þ 1]þ.

9-Substituted Benzo[de]chromene-7,8-dione
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7-Methoxy-3,9-dimethylbenzo[de]chromene (VI)
Compound VI was prepared from 4a according to the procedure for
Compound V: yield 82%, white solid.[20] 1H NMR (500 MHz, CDCl3, d,
ppm) 1.85 (3H, d, J ¼ 1 Hz), 2.25 (3H, s), 3.92 (3H, s), 6.60 (1H, s), 6.68
(2H, m), 7.20 (1H, t, J ¼ 8.5 Hz), 7.63 (1H, t, J ¼ 8.5 Hz), 7.56 (1H, d,
J ¼ 8 Hz). ESI-MS m/z 227 [M þ 1]þ.
ACKNOWLEDGMENTS
We are indebted to the National Nature Science Foundation of China
(20472117), the Guangzhou City Science Foundation, the Guangdong
Provincial Science Foundation, the Scientific Research Foundation for the
Returned Overseas Chinese Scholars, and the Hong Kong Polytechnic University
Area of Strategic Development Fund for financial support of this study.
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