Iodine-catalyzed synthesis of 12-aryl-8,9,10,12-tetrahydro-benzo[a]xanthen- 11-one derivatives via multicomponent reaction

Article abstract of DOI:10.1080/00397910802638511

Iodine efficiently catalyzes the one-pot, three-component reaction of aryl aldehyde, 2-naphthol, and cyclic 1,3-dicarbonyl compound under solvent-free conventional heating conditions to afford the corresponding 12-aryl-8,9,10,12- tetrahydro-benzo[a]xanthe

Full text of DOI:10.1080/00397910802638511

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Iodine-Catalyzed Synthesis of
12-Aryl-8,9,10,12-tetrahydro-
benzo[a]xanthen-11-one
Derivatives via Multicomponent
Reaction
Rui-Zhi Wang a , Li-Feng Zhang b & Zhen-Shui Cui a
a College of Chemistry and Material Science, Hebei
Normal University, Shijiazhuang, China
b Department of Chemical and Environmental
Engineering, Hebei Chemical and Pharmaceutical
Vocational Technology College, Shijiazhuang, China
Version of record first published: 12 May 2009
To cite this article: Rui-Zhi Wang, Li-Feng Zhang & Zhen-Shui Cui (2009): Iodine-
Catalyzed Synthesis of 12-Aryl-8,9,10,12-tetrahydro-benzo[a]xanthen-11-one
Derivatives via Multicomponent Reaction, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 39:12, 2101-2107
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Synthetic Communications1, 39: 2101–2107, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802638511
Iodine-Catalyzed Synthesis of 12-Aryl-8,9,10,12-
tetrahydro-benzo[a]xanthen-11-one Derivatives
via Multicomponent Reaction
Rui-Zhi Wang,1 Li-Feng Zhang,2 and Zhen-Shui Cui1
1College of Chemistry and Material Science, Hebei Normal University,
Shijiazhuang, China
2Department of Chemical and Environmental Engineering, Hebei
Chemical and Pharmaceutical Vocational Technology College,
Shijiazhuang, China
Abstract: Iodine efficiently catalyzes the one-pot, three-component reaction of
aryl aldehyde, 2-naphthol, and cyclic 1,3-dicarbonyl compound under solvent-
free conventional heating conditions to afford the corresponding 12-aryl-
8,9,10,12-tetrahydro-benzo[a]xanthen-11-one derivatives. The present approach
offers several advantages such as shorter reaction times, good yields, low cost,
and mild reaction conditions.
Keywords: Aldehyde, iodine, multicomponent reaction, b-naphthol, solvent-free
conditions, xanthene
INTRODUCTION
Multicomponent reactions (MCRs) have attracted much attention as a
result of their synthetic efficiency, simplicity of operation, reduction of
isolation and purification steps, and minimization of costs, energy, time,
and waste production.[1–3]
Received August 5, 2008.
Address correspondence to Rui-Zhi Wang, College of Chemistry and Material
Science, Hebei Normal University, Shijiazhuang 050091, China. E-mail:
orgsynchem@gmail.com
2101

2102
R.-Z. Wang, L.-F. Zhang, and Z.-S. Cui
Scheme 1. Synthesis of 12-aryl-8,9,10,12-tetrahydro-benzo[a]xanthen-11-one
derivatives catalyzed by iodine.
Compounds containing a xanthene skeleton exhibit good biological
and pharmaceutical activities such as antibacterial, antiviral, and anti-
inflammatory activities. They have found application in industries such
as dyes, laser technologies, and pH-sensitive fluorescent material to
monitor changes in intracellular pH.[4–7] Therefore, several approaches
have been reported for their synthesis.[8] Despite the available methods,
little attention has been paid to synthesis of 12-aryl-8,9,10,12-tetrahy-
dro-benzo[a]xanthen-11-one derivatives. To the best of our knowledge,
only one procedure was reported in the literature,[9] in which NaHSO4ꢀ
SiO2 was used as a catalyst and the reaction was carried out in refluxing
1,2-dichloreethane. However, this procedure involves the use of harmful
volatile organic solvent and extended reaction times. Thus, it is necessary
to further develop an efficient and convenient method to construct this
type of heterocyclic compounds.
In recent years, molecular iodine has emerged as an inexpensive and
easily available catalyst for various organic transformations.[10–18] It is
therefore of interest to examine the behavior of molecular iodine as cat-
alyst in the synthesis of xanthene-based compounds. Herein, we report a
new method for the synthesis of 12-aryl-8,9,10,12-tetrahydro-benzo[a]-
xanthen-11-one derivatives via a one-pot, three-component reaction of
aldehydes with b-naphthol and cyclic 1,3-dicarbonyl compound by use
of molecular iodine as catalyst under solvent-free conditions (Scheme 1).
RESULTS AND DISCUSSION
In an initial endeavor, a mixture of 2-naphthol (1 mmol), 4-chlorobenzal-
dehyde (1 mmol), and 5,5-dimethyl-1,3-cyclohexanedione (1.2 mmol) in
the presence of iodine (0.1 mmol) was stirred in 1,2-dichloroethane under
reflux conditions. After 3 h, only 38% of the expected product 4e was
obtained. This is probably because the use of solvent decreases the cata-
lytic efficiency of iodine. It has been shown that many reactions proceed
efficiently under solvent-free conditions.[19] To improve the yield, the
ꢁ
same reaction was carried out under solvent-free conditions at 60 C.
A significant improvement was observed, and the yield of 4e was increa-
sed to 95%. The effect of amount of catalyst on the yield and rate was

Iodine-Catalyzed Multicomponent Reaction
2103
also investigated. It was found that 10 mmol% of catalyst was enough for
a fairly good yield. Lesser amounts gave a poor yield even after a long
reaction time, and greater amounts did not obviously increase the yield
of the product. Meanwhile, we also tested the effect of reaction tempera-
ture on the catalyzed reaction. When the reaction was carried out at
ꢁ
60 C, the maximum yield was obtained in a short reaction period (1 h).
To extend the scope of the reaction and to generalize the procedure, a
variety of electronically divergent aromatic aldehydes, 5,5-dimethyl-1,3-
cyclohexanedione, and b-naphthol were examined, and the results are
summarized in Table 1. In all cases, aromatic aldehydes carrying either
an electron-withdrawing group or an electron-donating group reacted
successfully and gave the products in good to excellent yields. The results
proved that this methods is superior to previously reported methods in
terms of yields and reaction times.[9] It is observed that substituents in
the aromatic ring of aldehydes have a delicate effect on the reaction
process. Aromatic aldehydes with electron-withdrawing groups reacted
faster than those with electron-donating groups. To further expand the
scope of the present method, the replacement of 5,5-dimethyl-1,3-
cyclohexanedione with 1,3-cyclohexanedione was examined. To our
delight, under the same conditions, the reactions proceeded steadily to
afford a series of xanthene-based compounds in good yields.
A plausible mechanism was proposed in Scheme 2. After reviewing
the literature,[20] we think that iodine catalyzes the reaction as a mild
Table 1. Iodine-catalyzed preparation of 12-aryl-8,9,10,12-tetrahydro-benzo[a]
xanthen-11-one derivatives under solvent-free conditions
Entry
Aldehydes
R
Time (min)
Yield (%)a
Mp (ꢁC)
a
b
c
d
e
f
PhCHO
Me
Me
Me
Me
Me
Me
Me
H
H
H
H
H
75
85
90
65
60
60
45
70
90
95
60
50
55
90
89
88
82
95
95
90
88
87
86
94
92
91
149–150[21]
175–176
208–209[9]
150–151[9]
187–188[9]
186–187
175–176[21]
188–189[9]
205–206
181–182[21]
205–206[21]
235–236[21]
234–235[21]
4-MeC6H4CHO
4-MeOC6H4CHO
4-OHC6H4CHO
4-ClC6H4CHO
4-BrC6H4CHO
4-NO2C6H4CHO
PhCHO
4-MeC6H4CHO
4-MeOC6H4CHO
4-ClC6H4CHO
3-NO2C6H4CHO
4-NO2C6H4CHO
g
h
i
j
k
l
m
H
aIsolated yield.

2104
R.-Z. Wang, L.-F. Zhang, and Z.-S. Cui
Scheme 2. Hypothetical mechanism for the synthesis of xanthene-based compounds.
Lewis acid. First, the condensation of 2-naphthol with aldehydes produced
ortho-quinone methides (o-QMs) in the presence of molecular iodine.
Then, the trapping of o-QMs with dimedone formed intermediates 5,
which were cyclized and then dehydrated to give the corresponding
products 4.
In conclusion, molecular iodine has proved to be a useful and novel
catalyst for the synthesis of 12-aryl-8,9,10,12-tetrahydro-benzo[a]-
xanthen-11-one derivatives in good yields and short reaction times. The
use of inexpensive and readily available molecular iodine made this
procedure simple, convenient, and practical.
EXPERIMENTAL
Melting points were recorded on an X-4 apparatus and are uncorrected.
Infrared (IR) spectra were obtained using a Shimadzu Fourier transform
(FT)IR–8900 spectrometer using KBr optics. 1H NMR spectra were
recorded with a Varain Mercury Plus 400 spectrometer in CDCl3 using
tetramethylsilane (TMS) as internal standard. Mass spectra (MS) were
recorded on a VG-7070E mass spectrophotometer. Elemental analyses
were performed on Vario EL III CHNOS elemental analyzer.
General Procedure for the Preparation of 14-Aryl-14 H-
dibenzo[a,j]xanthene Derivatives
A mixture of aldehydes (1 mmol), b-naphthol (1 mmol), cyclic 1,3-
dicarbonyl compound (1.2 mmol), and I2 (0.1 mmol) was ground and
ꢁ
heated at 60 C for a specified time. After completion of the reaction
as indicated by thin-layer chromatography (TLC), the system was cooled
to room temperature. The mixture was treated with aqueous Na2S2O3
and then extracted with ethyl acetate (2 ꢂ 10 mL). The combined organic

Iodine-Catalyzed Multicomponent Reaction
2105
layer was dried over anhydrous Na2SO4 and evaporated under reduced
pressure. The crude product was purified by silica-gel column chroma-
tography using ethyl acetate–hexane (1:10) as eluent to afford pure
products. The identification and characterization of the products were
carried out by comparing their physical and spectroscopic data with
those of known samples.[9] The purity of the presently synthesized
1
compounds was demonstrated by TLC and H NMR.
Spectral Data for Selected Compounds
9,9-Dimethyl-12-p-tolyl-8,9,10,12-tetrahydro-benzo[a]
xanthen-11-one (4b)
ꢁ
White solid; mp 175–176 C; IR (KBr): 2947, 2869, 1647, 1596, 1508,
1
1400, 1371, 1226, 1186, 827, 812 cmꢃ1; H NMR (400 MHz, CDCl3) d:
0.97 (s, 3H), 1.12 (s, 3H), 2.19 (s, 3H), 2.25 and 2.30 (AB system,
J ¼ 16.0 Hz, 2H, CHaCHbCO), 2.57 (s, 2H), 5.67 (s, 1H), 6.98 (d, J ¼
7.6 Hz, 2H), 7.21–7.38 (m, 4H), 7.43 (t, J ¼ 8.0 Hz, 1H), 7.76 (t,
J ¼ 7.6 Hz, 2H), 8.01 (d, J ¼ 8.4 Hz, 1H) ppm; MS (EI, 70 eV) m=z (%):
368 (Mþ, 88), 277 (100), 221 (26), 193 (18), 165 (16), 55 (8). Anal. calcd.
for C26H24O2: C, 84.75; H, 6.57. Found: C, 84.66; H, 6.42.
12-(4-Bromophenyl)-9,9-dimethyl-8,9,10,12-tetrahydro-benzo[a]
xanthen-11-one (4f)
ꢁ
White solid; mp 186–187 C; IR (KBr): 2962, 2868, 1643, 1593, 1483,
1H NMR (400 MHz,
1400, 1375, 1220, 1174, 1145, 1008, 837 cmꢃ1
;
CDCl3) d: 0.97 (s, 3H), 1.12 (s, 3H), 2.25 and 2.30 (AB system,
J ¼ 16.4 Hz, 2H, CHaCHbCO), 2.57 (s, 2H), 5.67 (s, 1H), 7.20–7.46 (m,
7H), 7.78 (t, J ¼ 7.6 Hz, 2H), 7.89 (d, J ¼ 8.4 Hz, 1H) ppm; MS (EI,
70 eV) m=z (%): 434 (M þ 2, 42), 432 (Mþ, 40), 277 (100), 221 (23), 193
(12), 165 (16), 55 (8). Anal. calcd. for C25H21BrO2: C, 69.29; H, 4.88.
Found: C, 69.12; H, 4.93.
12-p-Tolyl-8,9,10,12-tetrahydro-benzo[a]xanthen-11-one (4i)
ꢁ
White solid; mp 205–206 C; IR (KBr): 2950, 2871, 1651, 1595, 1508,
1H NMR
1402, 1373, 1226, 1188, 1176, 1126, 1137, 954, 817 cmꢃ1
;
(400 MHz, CDCl3) d: 1.91–1.94 (m, 2H), 2.20 (s, 3H), 2.31–2.48 (m,
2H), 2.55–2.76 (m, 2H), 5.70 (s, 1H), 6.98 (d, J ¼ 8.0 Hz, 1H), 7.03
(d, J ¼ 8.0 Hz, 1H), 7.19 (d, J ¼ 8.0 Hz, 1H), 7.24 (d, J ¼ 8.0 Hz, 1H),

2106
R.-Z. Wang, L.-F. Zhang, and Z.-S. Cui
7.31–7.44 (m, 3H), 7.76 (d, J ¼ 8.0 Hz, 2H), 7.97 (d, J ¼ 8.4 Hz, 1H) ppm;
MS (EI, 70 eV) m=z (%): 340 (Mþ, 42), 325 (8), 308 (28), 277 (124), 249
(100), 216 (40), 165 (10), 55 (12). Anal. calcd. for C24H20O2: C, 84.68;
H, 5.92. Found: C, 84.79; H, 6.06.
12-(4-Methoxyphenyl)-8,9,10,12-tetrahydro-benzo[a]
xanthen-11-one (4j)
White solid, mp 181–182ꢀC; IR (KBr): 2945, 2875, 1651, 1595, 1460, 1377,
1251, 1226, 1188, 1174, 1033, 952, 748 cmꢁ1; 1H NMR (400 MHz, CDCl3) d:
1.91–2.08 (m, 2H), 2.31–2.48 (m, 2H), 2.57–2.76 (m, 2H), 3.69 (s, 3H), 5.69
(s, 1H), 6.70 (d, J ¼ 8.0 Hz, 2H), 7.23–7.44 (m, 5H), 7.76 (t, J¼ 8.4 Hz, 2H),
7.95 (d, J ¼ 8.0 Hz, 1H) ppm; MS (EI, 70 eV) m=z (%): 356 (Mþ, 65), 355
(95), 324 (28), 299 (22), 249 (100), 216 (8), 165 (20), 55 (12). Anal. calcd.
for C24H20O3: C, 80.88; H, 5.66. Found: C, 80.74; H, 5.81.
ACKNOWLEDGMENTS
We are grateful for financial support from Hebei Normal University
(L2008Y05) and the Nature Science Foundation of Hebei Province
(B2008000149).
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