Oxidative cyclization of 3-cinnamoyltropolones with I2/DMSO/ H2SO4 system

Article abstract of DOI:10.1002/jhet.150

(Chemical Equation Presented) In this study, a facile and general method synthesizing flavone-like 2-aryl-4,9-dihydrocyclohepta[b]-pyran-4,9-diones (2a-y) from 3-cinnamoyltropolones (1a-y) via oxidative cyclization reaction by using I₂/DMSO/H

Full text of DOI:10.1002/jhet.150

November 2009
Oxidative Cyclization of 3-Cinnamoyltropolones with
I2/DMSO/H2SO4 System
1107
Wentao Gao,a* Yang Li,a Hong Zhang,a Mingqin Chang,a
and Kimiaki Imafukub*
aInstitute of Superfine Chemicals, Bohai University, Jinzhou 121000, China
bDepartment of Chemistry, Graduate School of Science and Technology, Kumamoto University,
Kurokami, Kumamoto 860, Japan
*E-mail: isfc@bhu.edu.cn or imafuku@aster.sci.kumamoto-u.ac.jp
Received December 1, 2008
DOI 10.1002/jhet.150
Published online 27 October 2009 in Wiley InterScience (www.interscience.wiley.com).
In this study, a facile and general method synthesizing flavone-like 2-aryl-4,9-dihydrocyclohepta[b]-
pyran-4,9-diones (2a–y) from 3-cinnamoyltropolones (1a–y) via oxidative cyclization reaction by using
I2/DMSO/H2SO4 system is described. The method was found to be successfully applicable to a wide
range of 3-cinnamoyltropolone derivatives and characterized by generality, compatibility, and easy
work-up procedures.
J. Heterocyclic Chem., 46, 1107 (2009).
INTRODUCTION
4,9-dihydrocyclohepta[b]pyran-4,9-diones was based on
the reactions of 3-acetyltropolone with methoxyl- and/or
hydroxy-substituted benzaldehydes in the presence of
triethyl orthoformate and with perchloric acid as the
oxidant. However, Wang’s procedure is also limited
to methoxy- and/or hydroxy-substituted benzaldehyde
derivatives and is not applicable to a large number of
starting materials. In view of the aforementioned draw-
backs, we deemed it desirable to develop a simpler,
more efficient, and broadly applicable synthetic
approach with a wide range of substrates to overcome
the previously mentioned disadvantages. Recently, a
method has been reported for the synthesis of flavone
compounds from 20-hydroxychalcone via oxidative
cyclization reaction using I2/DMSO/H2SO4 system
[10,11]. The reactions were completed in a few hours at
100ꢀC in DMSO, and a catalytic amount of I2 and con-
centrated H2SO4 to give flavone compounds in good
yields. In connection with our studies, we envisioned
that the system could also be applied to 3-cinnamoyltro-
polones, from which flavone-like compounds 2-aryl-4,9-
dihydrocyclohepta[b]pyran-4,9-diones may be synthe-
sized through oxidative cyclization reaction. Indeed, this
was found to be the case and, to the best of our knowl-
edge, it is the first example of the application of the
I2/DMSO/H2SO4 system in the oxidative cyclization
reaction of 3-cinnamoyltropolones.
Heterocycle-fused troponoids are a type of com-
pounds with physiological activities such as anticancer
[1], germicide, antiphlogistic [2], antihypertension [3],
and antidiabetic [4]. They are included in many natural
products such as alkaloids and antibiotics. For example,
a new antimalarial tropolone, named cordytropolone,
was discovered in a culture broth of Cordyceps [5]. Het-
erocycle-fused troponoids can be synthesized in many
ways, among which one was to oxidize the side chain
of tropolone for cyclization. For instance, it was
reported that flavone-like heterocycle-fused troponoid
compounds, 2-aryl-4,9-dihydrocyclohepta[b]pyran-4,9-
diones, were obtained by oxidative cyclization of
3-cinnamoyltropolones using selenium dioxide [6] or
2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) [7] as oxi-
dative reagents. We have ever reported that reactions of
unsubstituted 3-cinnamoyltropolone or 3-cinnamoyl-5-
phenylazo-substituted tropolone with excess bromine
can also give heterocycle-fused flavone-like compounds
[8]. Although these practical syntheses have been
described so far, these methods, however, are limited to
unsubstituted or specifically substituted 3-cinnamoyltro-
polones and lack generality, compatibility, easy work-up
procedures, regiochemical control, and high yields.
Another approach reported by Wang et al. [9] to 2-aryl-
C
V
2009 HeteroCorporation

1108
W. Gao, Y. Li, H. Zhang, M. Chang, and K. Imafuku
Vol 46
Table 1
Yields and melting points of compounds 2.
RESULTS AND DISCUSSION
Scheme 1 outlines the synthetic sequence used in our
laboratories for the preparation of heterocycle-fused fla-
vone-like compounds 2a–y. The starting materials of
our study were readily prepared from 3-acetyltropolone
and various benzaldehyde derivatives by aldol condensa-
tion [6].
Substrate
R
Product Yield (%)
mp (ꢀC)
1a
H
2a
52 ([6]: 70)
202–204
([6]: 201–202)
190–192
197–199
216–218
1b
1c
1d
4-Me
4-Et
2b
2c
2d
59
60
2-OMe
3-OMe
4-OMe
41 ([6]: 56)
To check the feasibility of this approach using
I2/DMSO/H2SO4 system and show a comparable result,
we initially chose the representative unsubstituted 3-cin-
namoyltropolone (1a) and methoxy-substituted 3-cinna-
moyltropolones 1d–f and 1q–t to perform the initial
experiments because their oxidative cyclization reactions
have been previously reported by using different oxida-
tive reagents [6–9,12]. As reported earlier, using hydro-
gen peroxide in the presence of alkali substrates, 1a,
1d–f, and 1q–t, could not be converted into flavone-like
compounds [12]. In [6], only 1a and 1d–f could be con-
verted to corresponding flavone-like products 2a and
2d–f while using SeO2 as oxidative cyclization reagent.
Moreover, this method has some drawbacks, such as the
use of toxic reagent, tedious work-up procedures, and
narrow scope of the substrates. When under the action
of elemental bromine [8], only substrate 1a could react
to give flavone-like products, but the bromination reac-
tion of the aromatic ring of 1a also occurred at the same
time under this condition. In the oxidation cyclization of
3-cinnamoyltropolones with DDQ [7], only unsubsti-
tuted and 3-methoxy-substituted 3-cinnamoyltropolones
(1a, 1e) gave the flavone-like compounds 2a and 2e,
while the other methoxy-substituted ones, such as 1d,
1f, and 1q–t, are often limited and gave aurone-like
products. However, in our experiment, upon treatment
with I2/DMSO/H2SO4 system at 100ꢀC for 10 h, these
substrates were all smoothly converted to their corre-
sponding flavone-like compounds (2a, 2d–f, and 2q–t),
which are acceptable to good yields. Thus, I2/DMSO/
H2SO4 system offered a general method for the oxida-
tive cyclization reaction of a wide variety of 3-cinna-
([6]: 218–220)
211–213
1e
1f
2e
2f
55 ([6]: 50)
70 ([6]: 46)
([6]: 212–214)
238–240
([6]: 231–233)
198–201
212–213
1g
1h
1i
1j
1k
1l
1m
1n
1o
1p
1q
3-OPh
2-Cl
3-Cl
4-Cl
2-Br
2g
2h
2i
2j
2k
2l
65
58
34
66
200–202
288–299
52
61
222–223
252–254
4-Br
3-CN
4-CN
3-NO2
4-NO2
3,4-(OCH2O)
2m
2n
2o
2p
2q
80
46
75
296–298
301–302
298–300
304–305
281–283
71
92 ([9]: 74)
([9]: 278–279)
192–194
186–188
1r
1s
1t
2,3-(OMe)2
2,5-(OMe)2
3,4-(OMe)2
2r
2s
2t
63
33
81 ([9]: 64)
268–270
([9]: 264–265)
218–220
226–227
1u
1v
1w
1x
1y
2,3-(Cl)2
2,4-(Cl)2
2u
2v
2w
2x
2y
53
44
53
59
63
3,5-(Cl)2
3,4-(Cl)2
3,4,5-(OMe)3
272–274
260–261
249–251
moyltropolone substrates. The compounds 2a, 2d–f, 2q,
and 2t are known compounds and their structures were
unambiguously confirmed by the physical and spectro-
scopic data, which were in good agreement with the
reported values. Through an effort to optimize the reac-
tion conditions, such as the reaction temperature and the
amount of the I2/DMSO/H2SO4 system, we found that
the best results were achieved when the reactions were
conducted at a temperature of 100ꢀC with a ratio of
1 mmol 3-cinnamoyltropolone to 8 mL DMSO, 10 mg
I2, and 3–4 drops of concentrated H2SO4. We also found
that the addition of increased amounts of I2 or H2SO4
lowered the purity and yield of products.
Scheme 1
To establish the generality and applicability of this
method, a wide variety of 3-cinnamoyltropolones con-
taining electron-donating (such as alkyl or alkoxyl
group) and electron-withdrawing (such as cyano, nitro,
or halide groups) substituents were subjected to the
same set of experiments to furnish the corresponding
flavone-like compounds. The results summarized in
Table 1 indicated the scope and generality of the oxida-
tion cyclization reaction with respect to various
3-cinnamoyltropolones.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2009 Oxidative Cyclization of 3-Cinnamoyltropolones with I2/DMSO/H2SO4 System
1109
From Table 1, we could see that this method was
found to be effective for both electron-donating and
electron-withdrawing substituents to afford flavone-like
products in moderate to good yields. For example,
3-cinnamoyltropolones, 1c, 1f, and 1q, bearing electron-
donating groups on the benzene ring were reacted to
give the corresponding products: 2-(4-ethylphenyl)-4,9-
dihydrocyclohepta[b]pyran-4,9-dione (2c), 2-(4-methox-
yphenyl)-4,9-dihydrocyclohepta[b]pyran-4,9-dione (2f),
and 2-(1,3-benzodioxol-5-yl)-4,9-dihydrocyclohepta[b]-
pyran-4,9-dione (2q) in 60%, 70%, and 92% yields,
respectively. On the other hand, 3-cinnamoyltropolones,
1m, 1o, and 1x, bearing electron-withdrawing groups
gave the following products: 2-(3-cyanophenyl)-4,9-
dihydrocyclohepta[b]pyran-4,9-dione (2m), 2-(3-nitro-
phenyl)-4,9-dihydrocyclohepta[b]pyran-4,9-dione (2o),
hydroxyl group in the tropolone ring had taken part in
the reaction.
We believe that this method is the simplest route for
the preparation of a wide range of flavone-like com-
pounds, requiring only simple, cheap reagent, and mild
conditions.
EXPERIMENTAL
Melting points (uncorrected) were determined using WRS-
1B melting points apparatus. The 1H NMR (400 MHz) and
13C NMR (100 MHz) spectra were recorded with a Varian
Inova 400 NMR spectrometer at 400 MHz. The reported
chemical shifts were against TMS. The mass spectra were
determined using an MSD VL ESI1 spectrometer. Elemental
analysis was performed using an Elementar Vario EL-III ele-
ment analyzer. The progress of reactions was monitored by
TLC on silica gel GF254 using ethyl acetate as eluent.
and
2-(3,4-dichlorophenyl)-4,9-dihydrocyclohepta[b]-
pyran-4,9-dione (2x) in 80%, 75%, and 59% yields,
respectively. Thus, we concluded that the electronic na-
ture of the substituents on 3-cinnamoyltropolones has no
significant effect on this reaction. Among them, the
compounds 2b–c, 2g–p, 2r–s, and 2u–y have never
been reported, and their structures were confirmed by
General procedure for the reaction of 3-cinnamoyltropo-
lones 1a–y with I2/DMSO/H2SO4 system. To a solution of
3-cinnamoyltropolones (1 mmol) in 8 mL DMSO, 3–4 drops
of concentrated H2SO4 were added. The mixture obtained was
stirred for 10 min at 100ꢀC, and then I2 (10 mg) was added to
the mixture and continued to stir at the same temperature.
After 10–24 h, the completion of reaction was monitored by
TLC, the mixture was cooled to room temperature, and the
precipitate formed was filtered, washed with water, and dried
to yield crude 2-aryl-4,9-dihydrocyclohepta[b]pyran-4,9-diones,
which was purified by recrystallization to give pure 2-aryl-4,9-
dihydrocyclohepta[b]pyran-4,9-diones 2a–y in 33–92% yield.
2-Phenyl-4,9-dihydrocyclohepta[b]pyran-4,9-dione (2a). This
compound was obtained as yellow needles (1,4-dioxane); IR
(potassium bromide): m 3058 (CH), 1660 (tropone CO), 1600
(pyran CO), 1520, 1510, 1390, 1190, 1120, 900, 820, 770, 690
1
IR, H NMR, 13C NMR, and MS. These results showed
that our protocol could tolerate a variety of functional
groups on the benzene ring. However, we found that
when the benzene ring of 3-cinnamoyltropolones was
replaced with the pyridine ring, the reaction became
complex under the same conditions and a prolonged
reaction time of more than 48 h provided only a trace
amount of oxidation cyclization products.
1
cmꢁ1; H NMR (CF3COOD, 400 MHz): d 8.13ꢁ9.06 ppm (m,
The ease of isolation of compounds 2a–y was nota-
ble; after aqueous work-up, flavone-like compounds 2a–
y were isolated as the main products and their structures
were analyzed. When the compounds were developed
on thin-layer chromatography (TLC; silica gel: GF254,
developing agent: ethyl acetate), there was only one
main spot with no tailing. The compounds had the nega-
tive coloring test with iron (III) chloride in methanol
solution. The IR spectrum exhibited an absence of
hydroxyl group, which appeared in 3-cinnamoyltropo-
lones, and the presence of two typical carbonyl absorp-
tions for the tropone and pyran moiety at about 1640
and 1600 cmꢁ1, respectively. The 1H NMR spectrum
showed the absence of a hydroxy OH signal and the
presence of one signal attributable to the proton of the
pyran ring in addition to the signals of other groups. In
13C NMR spectra, all the synthesized compounds
showed peaks in the 180–183 and 169–172 ppm range
for two carbonyl carbons of tropone and pyran (detailed
spectral data are given in the ‘‘Experimental’’ section).
In addition, the structure assigned for this reaction prod-
uct was fully supported by their mass spectrum as well
as their elemental analysis. All these facts show that the
10H, ArH, PhH, C¼¼CH); 13C NMR (CF3COOD, 100 MHz): d
182.78, 182.65, 171.54, 163.09, 144.53, 138.70, 135.84,
131.83, 130.72, 129.78, 128.69, 119.91, 117.10, 114.28,
111.47, 109.29; ms: m/z 251 (Mþ1)þ. Anal. Calcd for
C16H10O3: C, 76.79; H, 4.03. Found: C, 76.82; H, 3.99.
2-(4-Methylphenyl)-4,9-dihydrocyclohepta[b]pyran-4,9-
dione (2b). This compound was obtained as yellowish gray
needles (1,4-dioxane); IR (potassium bromide): m 3066 (CH),
2970 (CH), 1640 (tropone CO), 1590 (pyran CO), 1510, 1470,
1420, 1380, 1350, 1300, 1185, 1120, 1040, 890, 820, 710
1
cmꢁ1; H NMR (CF3COOD, 400 MHz): d 7.93ꢁ8.92 (m, 9H,
ArH, PhH, C¼¼CH), 2.97 ppm (s, 3H, CH3); 13C NMR
(CF3COOD, 100 MHz): d 182.43, 182.00, 172.43, 162.58,
161.13, 144.39, 144.4, 138.80, 135.28, 131.65, 129.07, 126.71,
119.95, 117.14, 114.32, 111.50, 108.25, 21.39 ppm; ms: m/z
265 (Mþ1)þ. Anal. Calcd for C17H12O3: C, 77.26; H, 4.58.
Found: C, 77.37; H, 4.53.
2-(4-Ethylphenyl)-4,9-dihydrocyclohepta[b]pyran-4,9-
dione (2c). This compound was obtained as yellow needles
(ethanol); IR (potassium bromide): m 3070 (CH), 2985 (CH),
1640 (tropone CO), 1590 (pyran CO), 1520, 1505, 1420, 1375,
1220, 1110, 960, 840, 820, 700 cmꢁ1 1H NMR (CF3COOD,
;
400 MHz): d 7.29–8.33 (m, 9H, ArH, PhH, C¼¼CH), 2.60–
2.67 (q, 2H, CH2, J ¼ 7.6 Hz, 14.8 Hz), 1.38 ppm (t, 3H,
CH3, J ¼ 6.2 Hz); 13C NMR (CF3COOD, 100 MHz): d
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1110
W. Gao, Y. Li, H. Zhang, M. Chang, and K. Imafuku
Vol 46
182.66, 182.22, 172.31, 162.82, 156.63, 146.73, 144.54,
138.94, 135.35, 133.74, 132.21, 131.59, 129.29, 127.08,
120.09, 117.27, 114.45, 111.64, 108.55, 30.08, 14.72, and
14.54 ppm; ms: m/z 279 (Mþ1)þ. Anal. Calcd for C18H14O3:
C, 77.68; H, 5.07. Found: C, 77.74; H, 4.99.
285 (Mþ1)þ. Anal. Calcd for C16H9ClO3: C, 67.50; H, 3.19.
Found: C, 67.64; H, 3.10.
2-(3-Chlorophenyl)-4,9-dihydrocyclohepta[b]pyran-4,9-
dione (2i). This compound was obtained as yellow solids
(1,4-dioxane); IR (potassium bromide): m 3060 (CH), 1650
(tropone CO), 1600 (pyran CO), 1520, 1470, 1410, 1365,
2-(2-Methoxyphenyl)-4,9-dihydrocyclohepta[b]pyran-4,9-
dione (2d). This compound was obtained as yellow needles
(1,4-dioxane); IR (potassium bromide): m 3060 (CH), 2920
(CH), 1630 (tropone CO), 1610 (pyran CO), 1590, 1515, 1490,
1
1305, 1180, 1110, 880, 700; H NMR (CF3COOD, 400 MHz):
d 7.46–8.54 ppm (m, 9H, ArH, PhH, C¼¼CH); 13C NMR
(CF3COOD, 100 MHz): d 182.46, 168.34, 162.45, 143.91,
138.14, 136.90, 134.55, 131.57, 129.33, 127.73, 125.90,
119.31, 116.49, 113.68, 110.86, 109.63 ppm; ms: m/z 285
(Mþ1)þ. Anal. Calcd for C16H9ClO3: C, 67.50; H, 3.19.
Found: C, 67.47; H, 3.16.
1450, 1380, 1295, 1250, 1190, 1015, 750 cmꢁ1 1H NMR
;
(CF3COOD, 400 MHz): d 7.51–8.73 (m, 9H, ArH, PhH,
C¼¼CH), 4.40 ppm (s, 3H, OCH3); 13C NMR (CF3COOD, 100
MHz): d 182.20, 181.97, 171.10, 162.21, 144.50, 138.89, 135.55,
132.04, 130.65, 127.79, 123.16, 120.07, 117.25, 114.44, 113.69,
113.07, 111.62, 56.53 ppm; ms: m/z 281 (Mþ1)þ. Anal. Calcd
for C17H12O4: C, 72.85; H, 4.32. Found: C, 72.91; H, 4.28.
2-(3-Methoxyphenyl)-4,9-dihydrocyclohepta[b]pyran-4,9-
dione (2e). This compound was obtained as yellow needles
(1,4-dioxane); IR (potassium bromide): m 3060 (CH), 2960
(CH), 1650 (tropone CO), 1590 (pyran CO), 1520, 1495, 1475,
2-(4-Chlorophenyl)-4,9-dihydrocyclohepta[b]pyran-4,9-
dione (2j). This compound was obtained as yellow needles
(1,4-dioxane); IR (potassium bromide): m 3060 (CH), 1650
(tropone CO), 1614 (pyran CO), 1512, 1490, 1410, 1370,
1340, 1286, 1175, 1091, 890, 832, 810, 700 cmꢁ1 1H NMR
;
(CF3COOD, 400 MHz): d 7.83–8.84 ppm (m, 9H, ArH, PhH,
C¼¼CH); 13C NMR (CF3COOD, 400 MHz): d 182.80, 169.48,
162.63, 144.42, 142.77, 138.70, 135.05, 131.93, 131.07,
129.72, 128.36, 119.91, 117.09, 114.28, 111.46, 109.46 ppm;
ms: m/z 285 (Mþ1)þ. Anal. Calcd for C16H9ClO3: C, 67.50;
H, 3.19. Found: C, 67.57; H, 3.12.
1
1440, 1385, 1350, 1290, 1180, 1115, 870, 790, 700 cmꢁ1; H
NMR (CF3COOD, 400 MHz): d 7.86–9.03 (m, 9H, ArH, PhH,
C¼¼CH), 4.57 ppm (s, 3H, OCH3); 13C NMR (CF3COOD, 100
MHz): d 182.98, 182.92, 170.35, 162.72, 144.66, 138.81,
135.24, 132.27, 129.76, 122.38, 121.44, 120.03, 117.22,
114.50, 111.58, 109.99, 56.72 ppm; ms: m/z 281 (Mþ1)þ.
Anal. Calcd for C17H12O4: C, 72.85; H, 4.32. Found: C, 72.81;
H, 4.35.
2-(2-Bromophenyl)-4,9-dihydrocyclohepta[b]pyran-4,9-
dione (2k). This compound was obtained as pale yellow nee-
dles (1,4-dioxane); IR (potassium bromide): m 3040 (CH),
1660 (tropone CO), 1600 (pyran CO), 1520, 1470, 1375, 1350,
1
1170, 1110, 1020, 820, 770, 700 cmꢁ1; H NMR (CF3COOD,
2-(4-Methoxyphenyl)-4,9-dihydrocyclohepta[b]pyran-4,9-
dione (2f). This compound was obtained as golden needles
(1,4-dioxane); IR (potassium bromide): m 3040 (CH), 2920
(CH), 1640 (tropone CO), 1600 (pyran CO), 1510, 1250, 1380,
400 MHz): d 7.81–9.13 ppm (m, 9H, ArH, PhH, C¼¼CH); 13C
NMR (CF3COOD, 100 MHz): d 183.07, 182.92, 170.49,
163.51, 145.10, 138.71, 135.33, 134.67, 132.64, 131.91,
130.16, 129.04, 122.52, 119.87, 117.05, 115.74, 114.24,
114.42 ppm; ms: m/z 331 (Mþ2)þ. Anal. Calcd for
C16H9BrO3: C, 58.38; H, 2.76. Found: C, 58.45; H, 2.82.
2-(4-Bromophenyl)-4,9-dihydrocyclohepta[b]pyran-4,9-
dione (2l). This compound was obtained as yellow needles
(1,4-dioxane); IR (potassium bromide): m 3050 (CH), 1650
(tropone CO), 1590 (pyran CO), 1510, 1485, 1410, 1370,
1270, 1190, 1110, 1020, 830, 810, 690 cmꢁ1 1H NMR
;
(CF3COOD, 400 MHz): d 7.60–8.82 (m, 9H, ArH, PhH,
C¼¼CH), 4.47 ppm (s, 3H, OCH3); 13C NMR (CF3COOD, 100
MHz): d 180.44, 178.99, 171.42, 165.85, 161.52, 142.64,
137.39, 133.93, 130.63, 128.84, 126.43, 120.35, 118.34,
116.02, 115.52, 112.70, 109.89, 105.33, 54.84 ppm; ms: m/z
281 (Mþ1)þ. Anal. Calcd for C17H12O4: C, 72.85; H, 4.32.
Found: C, 72.87; H, 4.29.
1180, 1110, 1075, 1010, 890, 830, 700 cmꢁ1 1H NMR
;
(CF3COOD, 400 MHz): d 7.77–8.77 ppm (m, 9H, ArH, PhH,
C¼¼CH); 13C NMR (CF3COOD, 100 MHz): d 182.78, 169.47,
163.48, 144.38, 138.67, 135.01, 134.11, 131.91, 130.96,
129.65, 128.78, 119.87, 117.06, 114.24, 111.42, 109.46 ppm;
ms: m/z 331 (Mþ2)þ. Anal. Calcd for C16H9BrO3: C, 58.38;
H, 2.76. Found: C, 58.28; H, 2.78.
2-(3-Phenoxyphenyl)-4,9-dihydrocyclohepta[b]pyran-4,9-
dione (2g). This compound was obtained as yellow needles
(1,4-dioxane); IR (potassium bromide): m 3050 (CH), 1640
(tropone CO), 1605 (pyran CO), 1585, 1520, 1480, 1440,
1
1380, 1350, 1270, 1230, 1210, 1175, 1110, 870, 700 cmꢁ1; H
NMR (CF3COOD, 400 MHz): d 7.00–8.44 ppm (m, 14H,
ArH, PhH, C¼¼CH); 13C NMR (CF3COOD, 100 MHz): d
183.23, 170.17, 163.54, 156.92, 144.79, 138.85, 135.25,
132.37, 131.90, 131.40, 130.04, 126.34, 125.04, 123.37,
121.14, 120.13, 117.77, 114.50, 111.68, 110.15 ppm; ms: m/z
343 (Mþ1)þ. Anal. Calcd for C22H14O4: C, 77.18; H, 4.12.
Found: C, 77.04; H, 4.32.
2-(3-Cyanophenyl)-4,9-dihydrocyclohepta[b]pyran-4,9-
dione (2m). This compound was obtained as yellow needles
(1,4-dioxane); IR (potassium bromide): m 3055 (CH), 2220
(CN), 1640 (tropone CO), 1600 (pyran CO), 1511, 1425, 1370,
1
1300, 1185, 1110, 850, 820, 700 cmꢁ1; H NMR (CF3COOD,
400 MHz): d 7.00–8.37 ppm (m, 9H, ArH, PhH, C¼¼CH); 13C
NMR (CF3COOD, 100 MHz): d 182.94, 171.96, 162.83,
155.82, 151.00, 144.74, 138.25, 136.39, 131.65, 129.52,
119.41, 116.59, 113.77, 110.96 ppm; ms: m/z 276 (Mþ1)þ.
Anal. Calcd for C17H9NO3: C, 74.18; H, 3.30. Found: C,
74.25; H, 3.28.
2-(2-Chlorophenyl)-4,9-dihydrocyclohepta[b]pyran-4,9-
dione (2h). This compound was obtained as pale yellow nee-
dles (1,4-dioxane); IR (potassium bromide): m 3058 (CH),
1655 (tropone CO), 1600 (pyran CO), 1511, 1472, 1430, 1370,
1339, 1170, 1010, 1028, 815, 760, 700 cmꢁ1 1H NMR
;
2-(4-Cyanophenyl)-4,9-dihydrocyclohepta[b]pyran-4,9-
dione (2n). This compound was obtained as yellow needles
(1,4-dioxane); IR (potassium bromide): m 3060 (CH), 2220
(CN), 1651 (tropone CO), 1590 (pyran CO), 1510, 1420, 1380,
(CF3COOD, 400 MHz): d 7.78–9.02 ppm (m, 9H, ArH, PhH,
C¼¼CH); 13C NMR (CF3COOD, 100 MHz): d 183.12, 182.94,
169.31, 163.66, 145.06, 138.72, 135.22, 132.19, 130.10,
128.58, 119.89, 117.57, 115.75, 114.26, 111.44 ppm; ms: m/z
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2009 Oxidative Cyclization of 3-Cinnamoyltropolones with I2/DMSO/H2SO4 System
1111
1
1295, 1160, 1110, 870, 810, 705 cmꢁ1; H NMR (CF3COOD,
400 MHz): d 8.13–9.09 ppm (m, 9H, ArH, PhH, C¼¼CH); 13C
NMR (CF3COOD, 100 MHz): d 183.18, 167.07, 163.59,
144.49, 138.82, 135.58, 135.13, 134.55, 132.03, 130.14,
129.07, 119.95, 117.13, 116.25, 114.31, 111.50 ppm; ms: m/z
276 (Mþ1)þ. Anal. Calcd for C17H9NO3: C, 74.18; H, 3.30.
Found: C, 74.04; H, 3.39.
NMR (CF3COOD, 100 MHz): d 182.46, 168.87, 162.93,
157.4, 153.80, 144.43, 138.60, 135.16, 131.12, 128.29, 125.04,
119.82, 118.64, 117.00, 116.32, 114.99, 114.19, 113.69,
111.38, 57.48, 56.66 ppm; ms: m/z 311 (Mþ1)þ. Anal. Calcd
for C18H14O5: C, 69.67; H, 4.55. Found: C, 69.78; H, 4.61.
2-(3,4-Dimethoxyphenyl)-4,9-dihydrocyclohepta[b]pyran-
4,9-dione (2t). This compound was obtained as yellow nee-
dles (1,4-dioxane); IR (potassium bromide): m 3070 (CH),
2940 (CH), 1635 (tropone CO), 1600 (pyran CO), 1510, 1465,
2-(3-Nitrophenyl)-4,9-dihydrocyclohepta[b]pyran-4,9-
dione (2o). This compound was obtained as yellow needles
(N,N-dimethylformamide); IR (potassium bromide): m 3090
(CH), 1645 (tropone CO), 1600 (pyran CO), 1540, 1530, 1500,
1430, 1380, 1330, 1265, 1150, 1020, 850, 805, 770, 700 cmꢁ1
;
1H NMR (CF3COOD, 400 MHz): d 7.05–8.29 (m, 8H, ArH,
PhH, C¼¼CH), 3.95 (s, 3H, OCH3), 3.92 ppm (s, 3H, OCH3);
13C NMR (CF3COOD, 100 MHz): d 182.55, 181.56, 171.44,
163.26, 156.21, 151.73, 150.24, 144.45, 138.98, 135.37,
131.29, 129.26, 125.48, 122.75, 120.09, 117.27, 116.02,
114.45, 113.13, 112.22, 111.64, 110.37, 107.92, 67.78, 56.78,
and 56.71 ppm; ms: m/z 311 (Mþ1)þ. Anal. Calcd for
C18H14O5: C, 69.67; H, 4.55. Found: C, 69.65; H, 4.57.
1390, 1355, 1180, 1110, 915, 820, 750, 710 cmꢁ1 1H NMR
;
(CF3COOD, 400 MHz): d 8.10–9.50 ppm (m, 9H, ArH, PhH,
C¼¼CH); 13C NMR (CF3COOD, 100 MHz): d 183.15, 166.86,
163.53, 149.87, 144.64, 138.91, 135.28, 134.62, 132.60,
132.19, 130.20, 128.94, 123.54, 120.03, 117.21, 114.40,
111.58, 111.37 ppm; ms: m/z 296 (Mþ1)þ. Anal. Calcd for
C16H9NO5: C, 65.09; H, 3.07. Found: C, 65.12; H, 3.11.
2-(2,3-Dichlorophenyl)-4,9-dihydrocyclohepta[b]pyran-
4,9-dione (2u). This compound was obtained as pale yellow
solids (1,4-dioxane); IR (potassium bromide): m 3065 (CH),
1660 (tropone CO), 1600 (pyran CO), 1515, 1410, 1370, 1340,
2-(4-Nitrophenyl)-4,9-dihydrocyclohepta[b]pyran-4,9-
dione (2p). This compound was obtained as deep yellow nee-
dles (1,4-dioxane); IR (potassium bromide): m 3060 (CH),
1650 (tropone CO), 1605 (pyran CO), 1515, 1425, 1370, 1350,
1170, 1110, 900, 870, 795 cmꢁ1 1H NMR (CF3COOD, 400
;
1175, 1110, 1040, 850, 810, 755, 695 cmꢁ1
;
1H NMR
MHz): d 7.67–8.98 ppm (m, 8H, ArH, PhH, CACH); 13C
NMR (CF3COOD, 100 MHz): d 183.75, 183.65, 169.13,
163.91, 145.77, 139.56, 137.12, 136.06, 133.23, 130.93,
129.88, 120.69, 117.87, 116.70, 115.06, 112.24 ppm; ms: m/z
319 (M)þ. Anal. Calcd for C16H8Cl2O3: C, 60.22; H, 2.53.
Found: C, 60.16; H, 2.63.
(CF3COOD, 400 MHz): d 7.84–8.73 ppm (m, 9H, ArH, PhH,
C¼¼CH); 13C NMR (CF3COOD, 100 MHz): d 182.94, 166.49,
162.90, 151.34, 144.32, 138.67, 136.62, 135.01, 131.81,
129.92, 125.48, 119.83, 117.01. 114.19, 111.81, 111.37 ppm;
ms: m/z 296 (Mþ1)þ. Anal. Calcd for C16H9NO5: C, 65.09; H,
3.07. Found: C, 65.16; H, 3.13.
2-(2,4-Dichlorophenyl)-4,9-dihydrocyclohepta[b]pyran-
4,9-dione (2v). This compound was obtained as colorless
needles (1,4-dioxane); IR (potassium bromide): m 3050 (CH),
1670 (tropone CO), 1604 (pyran CO), 1550, 1520, 1480, 1380,
2-(1,3-Benzodioxol-5-yl)-4,9-dihydrocyclohepta[b]pyran-
4,9-dione (2q). This compound was obtained as yellow nee-
dles (1,4-dioxane); IR (potassium bromide): m 3055 (CH),
2990 (CH), 1640 (tropone CO), 1595 (pyran CO), 1510, 1460,
1394, 1340, 1260, 1190, 1120, 1030, 920, 860, 850, 816, 700
1340, 1170, 1110, 890, 870, 820, 700 cmꢁ1
;
1H NMR
(CF3COOD, 400 MHz): d 7.84–9.06 ppm (m, 8H, ArH, PhH,
C¼¼CH); 13C NMR (CF3COOD, 100 MHz): d 183.81, 183.60,
168.72, 145.75, 142.19, 139.52, 136.01, 133.45, 130.82,
129.29, 120.66, 117.84, 116.59, 115.03, 112.22 ppm; ms: m/z
319 (M)þ. Anal. Calcd for C16H8Cl2O3: C, 60.22; H, 2.53.
Found: C, 60.19; H, 2.66.
1
cmꢁ1; H NMR (CF3COOD, 400 MHz): d 7.45–8.85 (m, 8H,
ArH, PhH, C¼¼CH), 6.56 ppm (s, 2H, OCH2O); 13C NMR
(CF3COOD, 100 MHz): d 182.09, 180.95, 172.2, 163.15,
156.18, 150.74, 144.28, 138.91, 135.46, 130.70, 128.31,
127.17, 123.34, 119.93, 117.11, 114.29, 111.48, 110.82,
108.38, 107.40, 104.13 ppm; ms: m/z 295 (Mþ1)þ. Anal.
Calcd for C17H10O5: C, 69.39; H, 3.43. Found: C, 69.33; H,
3.36.
2-(3,5-Dichlorophenyl)-4,9-dihydrocyclohepta[b]pyran-
4,9-dione (2w). This compound was obtained as yellow nee-
dles (1,4-dioxane); IR (potassium bromide): m 3040 (CH), 1650
(tropone CO), 1600 (pyran CO), 1560, 1520, 1425, 1375, 1345,
2-(2,3-Dimethoxyphenyl)-4,9-dihydrocyclohepta[b]pyran-
4,9-dione (2r). This compound was obtained as yellow nee-
dles (1,4-dioxane); IR (potassium bromide): m 3060 (CH),
2965 (CH), 1644 (tropone CO), 1609 (pyran CO), 1511, 1470,
1250, 1115, 860, 800, 700 cmꢁ1 1H NMR (CF3COOD, 400
;
MHz): d 7.30–8.37 ppm (m, 8H, ArH, PhH, C¼¼CH); 13C NMR
(CF3COOD, 100 MHz): d 183.07, 166.99, 163.04, 161.30,
151.73, 144.40, 138.84, 138.20, 135.02, 134.56, 133.17, 132.06,
130.03, 126.53, 119.94, 118.82, 117.12, 115.99, 114.82, 113.17,
111.49, 110.89 ppm; ms: m/z 319 (M)þ. Anal. Calcd for
C16H8Cl2O3: C, 60.22; H, 2.53. Found: C, 60.28; H, 2.51.
2-(3,4-Dichlorophenyl)-4,9-dihydrocyclohepta[b]pyran-
4,9-dione (2x). This compound was obtained as yellow nee-
dles (1,4-dioxane); IR (potassium bromide): m 3065 (CH),
1650 (tropone CO), 1600 (pyran CO), 1520, 1468, 1410, 1370,
1428, 1379, 1310, 1010, 910, 850, 760, 710 cmꢁ1 1H NMR
;
(CF3COOD, 400 MHz): d 7.45–8.65 (m, 8H, ArH, PhH,
C¼¼CH), 4.18 (s, 3H, OCH3), 4.11 ppm (s, 3H, OCH3); 13C
NMR (CF3COOD, 100 MHz): d 182.57, 167.99, 162.45,
153.73, 148.37, 144.21, 138.10, 134.61, 131.61, 126.79,
124.29, 122.54, 119.34, 118.75, 116.53, 114.02, 113.71,
110.90, 62.07, 56.06 ppm; ms: m/z 311 (Mþ1)þ. Anal. Calcd
for C18H14O5: C, 69.67; H, 4.55. Found: C, 69.63; H, 4.57.
2-(2,5-Dimethoxyphenyl)-4,9-dihydrocyclohepta[b]pyran-
4,9-dione (2s). This compound was obtained as orange nee-
dles (1,4-dioxane); IR (potassium bromide): m 3055 (CH),
2930 (CH), 1620 (tropone CO), 1590 (pyran CO), 1510, 1468,
1
1340, 1180, 1140, 1110, 1030, 900, 820, 710 cmꢁ1; H NMR
(CF3COOD, 400 MHz): d 7.27–8.32 ppm (m, 8H, ArH, PhH,
C¼¼CH); 13C NMR (CF3COOD, 100 MHz): d 183.00, 167.52,
163.40, 161.28, 144.41, 140.39, 138.86, 135.91, 135.06,
132.79, 132.08, 130.06, 127.30, 119.99, 117.17, 114.36,
111.54, 110.25 ppm; ms: m/z 319 (M)þ. Anal. Calcd for
C16H8Cl2O3: C, 60.22; H, 2.53. Found: C, 60.19; H, 2.65.
1
1429, 1370, 1330, 1170, 1140, 1070, 910, 820, 700 cmꢁ1; H
NMR (CF3COOD, 400 MHz): d 7.26–8.56 (m, 8H, ArH, PhH,
C¼¼CH), 4.15 (s, 3H, OCH3), 4.09 ppm (s, 3H, OCH3); 13C
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1112
W. Gao, Y. Li, H. Zhang, M. Chang, and K. Imafuku
Vol 46
[4] Treasurywala, A.; Palameta, B.; Boogri, T.; Bagli, J. U.S.
Pat. 4,337,265 (1981); Chem Abstr 1982, 97, 162818c.
2-(3,4,5-Trimethoxyphenyl)-4,9-dihydrocyclohepta[b]-
pyran-4,9-dione (2y). This compound was obtained as yellow
needles (1,4-dioxane); IR (potassium bromide): m 3060 (CH),
2935 (CH), 1650 (tropone CO), 1610 (pyran CO), 1520, 1470,
;
1410, 1370 cmꢁ1 1H NMR (CF3COOD, 400 MHz): d 7.87–
[5] Seephonkai, P.; Isaka, M.; Kittakoop, P.; Trakulnaleamsai,
S.; Rattanajak, R.; Tanticharoen, M.; Thebtaranonth, Y. J Antibiot
2001, 54, 751.
8.91 (m, 7H, ArH, PhH, C¼¼CH), 4.48–4.50 ppm (m, 9H,
OCH3); 13C NMR (CF3COOD, 100 MHz): d 182.90, 182.58,
169.80, 162.64, 154.64, 144.59, 142.97, 138.79, 135.19, 131.89,
129.56, 126.77, 119.94, 117.12, 114.31, 111.49, 109.61, 106.75,
62.25, 56.98 ppm; ms: m/z 341 (Mþ1)þ. Anal. Calcd for
C19H16O6: C, 67.05; H, 4.74. Found: C, 66.98; H, 4.87.
[6] Imafuku, K.; Yamane, A.; Matsumura, H. Yuki Gosei
Kagaku Kyokai Shi 1980, 38, 308.
[7] Imafuku, K.; Yamaguchi, K. Bull Chem Soc Jpn 1981, 54,
2855.
[8] Gao, W.-T.; Zhang, S.-F.; Yang, J.-Z. Chin Chem Lett
1999, 10, 1.
[9] Wang, D.-L.; Jin, Z.-T.; Imafuku, K. J Heterocycl Chem
1990, 27, 891.
REFERENCES AND NOTES
[10] Lu¨, Y.-X.; Mao, S.-F.; Li, G.-X.; Cai, M.-S. Chem J Chin
Univ 1987, 8, 331.
[1] Tsuruo, T.; Lido, H.; Tsukagoshi, S.; Sakirai, Y. Cancer
Res 1979, 39, 1063.
[11] Liu, J.-Y.; Huang, J.; Cai, M.-S. Chin J Org Chem 1991,
11, 191.
[2] Amano, T.; Hagashi, A.; Sawada, J.; Sasajima, M. U.S. Pat.
4,189,607, (1979) Chem Abstr 1980, 93, 7880r.
[3] Jehan, F. B.; Tibor, B. U.S. Pat. 4,258,188 (1980); Chem
Abstr 1981, 95, 7341g.
[12] Yamaguchi, K.; Imafuku, K.; Matsumura, H. Yuki Gosei
Kagaku Kyokai Shi 1980, 38, 998.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet