Ultrasound promoted efficient method for the cleavage of 3-aryl-2,3-epoxyl-1-phenyl-1-propanone with indole

Article abstract of DOI:10.1016/j.ultsonch.2009.09.004

An efficient synthesis of 3-aryl-3-hydroxy-2-(1H-indol-3-yl)-1-phenyl-1-propanone via the cleavage of epoxides with indole promoted by ultrasound irradiation was carried out in good yields by using montmorillonite K10-ZnCl₂ within 2-5 h at room

Full text of DOI:10.1016/j.ultsonch.2009.09.004

Ultrasonics Sonochemistry 17 (2010) 359–362
Contents lists available at ScienceDirect
Ultrasonics Sonochemistry
journal homepage: www.elsevier.com/locate/ultsonch
Ultrasound promoted efficient method for the cleavage
of 3-aryl-2,3-epoxyl-1-phenyl-1-propanone with indole
*
Ji-Tai Li , Ming-Xuan Sun, Ying Yin
College of Chemistry and Environmental Science, Hebei University, Key Laboratory of Analytical Science and Technology of Hebei Province,
Key Laboratory of Medical Chemistry and Molecular Diagnosis, Ministry of Education, Baoding 071002, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 24 June 2009
Received in revised form 28 August 2009
Accepted 14 September 2009
Available online 18 September 2009
An efficient synthesis of 3-aryl-3-hydroxy-2-(1H-indol-3-yl)-1-phenyl-1-propanone via the cleavage of
epoxides with indole promoted by ultrasound irradiation was carried out in good yields by using mont-
morillonite K10-ZnCl2 within 2–5 h at room temperature. This method provides several advantages such
as operational simplicity, high yield and mild conditions.
Ó 2009 Elsevier B.V. All rights reserved.
Keywords:
Cleavage
Epoxychalcone
Synthesis
Ultrasound irradiation
Supported catalyst
3-Aryl-3-hydroxy-2-(1H-indol-3-yl)-1-
phenylpropan-1-one
1. Introduction
into the corresponding carbonyl compounds catalyzed by the use
of montmorillonite K10 supported lithium chloride [5a], synthesis
The investigation of the chemistry of indoles has been, and con-
tinues to be, one of the most active areas of heterocyclic chemistry.
In particular, 3-substituted indole derivatives have received much
attention as important building blocks for the synthesis of many
natural products and other biologically active compounds [1]. Fur-
thermore, 3-substituted indoles are components of drugs and are
commonly found in molecules of pharmaceutical interest in a vari-
ety of the therapeutic areas [2].
Ultrasound irradiation has been considered as a clean and use-
ful protocol in organic synthesis during the last three decades,
compared with traditional methods, the procedure is more conve-
nient. A large number of organic reactions can be carried out in
higher yield, shorter reaction time and milder conditions under
ultrasound irradiation [3].
In recent years, catalysts supported on inorganic substrates
have received increasing attention as a means to develop conve-
nient and environmentally friendly catalysts [4]. Montmorillonite
K10 is known to behave as Bronsted acids in organic reactions. It
has been extensively used as efficient supports for a variety of cat-
alyst in synthetic organic chemistry. Such as conversion of alcohols
of 1,10-binaphthyls catalyzed by K10-FePLS120 [5b], synthesis of
bis(indol-3-yl)-methanes catalyzed by montmorillonite K10-ZnCl2
[5c], oxidation of olefins, chalcones and sulfides catalyzed by
montmorillonite K10 supported ceric ammonium nitrate [5d]. For
the past few years, we have investigated some applications of
montmorillonite K10-ZnCl2 with ultrasound and found that they
can improve organic reactions successfully [6].
The ring-opening reactions of epoxide with indole catalyzed by
using a various of catalysts, such as SiO2 [7], nanocrystalline tita-
nium(IV) oxide [8], InCl3 [9], InBr3 [10], LiClO4 [11], HBF4-SiO2
[12], RuCl3ÁnH2O [13], ionic liquid [Bmim][OTf] [14], Cp2ZrCl2
[15] and polymer-supported Indium Lewis acid [16] have been re-
ported. To the best of our knowledge, however, there is no example
for the synthesis of the title compound via ring-opening reaction of
3-aryl-2,3-epoxyl-1-phenyl-1-propanone with indole in litera-
tures. Herein, we wish to report an efficient synthesis of 3-aryl-
3-hydroxy-2-(1H-indol-3-yl)-1-phenyl-1-propanone via the ring-
opening reaction of 3-aryl-2,3-epoxyl-1-phenyl-1-propanone with
indole catalyzed by K10-ZnCl2 under ultrasound irradiation at
room temperature (Scheme 1).
2. Methods
* Corresponding author. Address: College of Chemistry and Environmental
Science, Hebei University, Wusi East Road, No. 180, Baoding 071002, PR China.
Fax: +86 312 5079628.
Melting points were uncorrected. 1H NMR spectra were mea-
sured on a Bruker AVANCE 400 (400 MHz) spectrometer using
E-mail address: lijitai@hbu.cn (J.-T. Li).
1350-4177/$ - see front matter Ó 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.ultsonch.2009.09.004

360
J.-T. Li et al. / Ultrasonics Sonochemistry 17 (2010) 359–362
catalyst was removed by filtration. Dichloromethane was evapo-
Ar
rated under reduced pressure to give the crude product, which
was separated by column chromatography on silica (200–300
mesh), eluted with petroleum ether or a mixture of petroleum
ether and ethyl acetate (3:1). The authenticity of the products
was established by the data of 1H NMR, MS.
OH
O
O
K10 - ZnCl2
u.s./r.t.
Ph
+
Ar
N
H
N
H
Ph
O
2
1
Compound 2a: solid, 1H NMR (400 MHz, CDCl3): dH 3.72 (d, 1H,
J = 5.8 Hz), 4.79 (s, 1H, O–H), 5.88 (dd, 1H, J = 5.8 Hz, J = 1.6 Hz),
6.95–7.95 (m, 15H, Ar–H), 8.19 (br s, 1H, N–H), m/z (ESI): 380
[M+K]+, 364 [M+Na]+.
Scheme 1. The synthesis of 3-aryl-3-hydroxy-2-(1H-indol-3-yl)-1-phenyl-1-
propanone.
Compound 2b: solid, 1H NMR (400 MHz, CDCl3): dH 3.82 (d, 1H,
J = 6.6 Hz), 4.88 (s, 1H, O–H), 5.92 (dd, 1H, J = 6.6 Hz, J = 1.6 Hz),
6.97–7.96 (m, 14H, Ar–H), 8.25 (br s, 1H, N–H), m/z (ESI): 386 [M]+.
Compound 2c: solid, 1H NMR (400 MHz, CDCl3): dH 2.24 (s, 3H,
CH3–), 3.69 (d, 1H, J = 7.0 Hz), 4.75 (s, 1H, O–H), 5.81(dd, 1H,
J = 6.9 Hz, J = 1.6 Hz), 6.84–7.95 (m, 14H, Ar–H), 8.12 (br s, 1H, N–
H), m/z (ESI): 354 [M-1]+.
TMS as the internal standard and CDCl3 as a solvent. MS were
determined on SHIMADZU GCMS-QP2010 spectrometer (ESI). Son-
ication was performed in Shanghai Branson-BUG25-06 ultrasonic
cleaner (with
a frequency of 25 kHz and a nominal power
250 W), the total acoustic power injected into the sample solution
was found to be 0.63 W by calorimetry [17]. 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 circulated water from
ultrasonic bath.
Compound 2d: solid, 1H NMR (400 MHz, CDCl3): dH 3.80(d, 1H,
J = 7.1 Hz), 4.76 (s, 1H, O–H), 5.87(dd, 1H, J = 7.1 Hz, J = 1.7 Hz),
6.83–7.94 (m, 14H, Ar–H), 8.21 (br s, 1H, N–H), m/z (ESI): 375
[M-1]+.
Compound 2e: solid, 1H NMR (400 MHz, CDCl3): dH 3.75 (d, 1H,
J = 6.9 Hz), 4.75 (s, 1H, O–H), 5.86 (dd, 1H, J = 6.9 Hz, J = 1.6 Hz),
6.65–7.94 (m, 14H, Ar–H), 8.17 (br s, 1H, N–H), m/z (ESI): 399
[M+Na]+, 415 [M+K]+.
2.1. Preparation of montmorillonite K10-ZnCl2
Montmorillonite K10-ZnCl2 was obtained by dissolving 5.44 g
ZnCl2 in anhydrous ethanol and then adding 10 g montmorillonite
K10. The mixture was stirred for 1 h at room temperature. The
anhydrous ethanol was removed under reduced pressure. The
resulting free flowing powder was dried at 120 °C for 4 h and then
stored in a desiccator until required. The content of ZnCl2 is about
35.2% [5c,6b].
Compound 2f: solid, 1H NMR (400 MHz, CDCl3): dH 3.81 (d, 1H,
J = 6.2 Hz), 4.87 (s, 1H, O–H), 5.95 (dd, 1H, J = 6.1, Hz, J = 1.6 Hz),
6.68–7.96 (m, 14H, Ar–H), 8.23 (br s, 1H, N–H), m/z (ESI): 386 [M]+.
Compound 2g: solid, 1H NMR (400 MHz, CDCl3): dH 3.77 (d, 1H,
J = 7.1 Hz), 4.72 (s, 1H, O–H), 5.84 (dd, 1H, J = 7.0 Hz, J = 1.9 Hz),
6.89–7.92 (m, 14H, Ar–H), 8.18 (br s, 1H, N–H), m/z (ESI): 420 [M]+.
Compound 2h: solid, 1H NMR (400 MHz, CDCl3): dH 3.81 (d, 1H,
J = 6.7 Hz), 4.72 (s, 1H, O–H), 5.85 (dd, 1H, J = 6.7 Hz, J = 1.6 Hz),
6.77–7.93 (m, 13H, Ar–H), 8.21 (br s, 1H, N–H), m/z (ESI): 411
[M+1]+, 433 [M+Na]+.
2.2. The preparation of 3-aryl-2,3-epoxyl-1-phenyl-1-propanone
In Ref. [18], the method to prepare 3-aryl-2,3-epoxyl-1-phenyl-
1-propanone was described.
Compound 2i: solid, 1H NMR (300 MHz, CDCl3): dH 3.81(d, 1H,
J = 6.6 Hz), 4.87(s, 1H, O–H), 5.92 (dd, 1H, J = 6.6 Hz, J = 1.5 Hz),
6.96–7.95 (m, 14H, Ar–H), 8.25 (br s, 1H, N–H), m/z (ESI): 385
[M-1]+.
2.3. The synthesis of 3-aryl-3-hydroxy-2-(1H-indol-3-yl)-1-phenyl-1-
propanone
Compound 2j: solid, 1H NMR (400 MHz, CDCl3): dH 3.54 (d, 1H,
J = 7.0 Hz), 3.96 (s, 3H, CH3O–), 4.72 (s, 1H, O–H), 5.83 (dd, 1H,
J = 7.0 Hz, J = 1.6 Hz), 6.89–7.96 (m, 14H, Ar–H), 8.15 (br s, 1H, N–
H), m/z (ESI): 372 [M+1]+.
Indole (117 mg, 1 mmol), 3-aryl-2,3-epoxyl-1-phenyl-1-propa-
none (1, 1 mmol), K10-ZnCl2 (193 mg, corresponding to 0.5 mmol
ZnCl2), dichloromethane (5 mL), were mixed in a 25 mL Erlen-
meyer flask. The mixture was irradiated in the water bath of the
ultrasonic cleaner or stirred at room temperature for the period
as indicated in Tables 1 and 2 (the reaction was followed by
TLC). The temperature is 25 °C inside the ultrasonic reactor upon
ultrasound, and the reaction temperature is also 25 °C upon stir-
ring during the reaction. After the completion of the reaction, the
3. Results and discussion
As shown in Table 1, the effects of the amount of catalyst on the
reaction were examined under ultrasound at room temperature.
Increasing the amount of the catalyst can improve the reaction
yields. For example, in the absence of K10-ZnCl2, 1,3-diphenyl-3-
hydroxy-2-(1H-indol-3-yl)-1-propanone was not obtained (entry
5), whereas using 193 mg K10-ZnCl2, the yield was 90% (entry 3).
But increasing the amount of K10-ZnCl2 to 385 mg, the yield de-
creased to 81% (entry 1).
We also observed the reaction catalyzed only by K10 or ZnCl2.
From the results in Table 1, Adsorbing ZnCl2 on K10 enhances
the activity of ZnCl2 and K10. K10-ZnCl2 can achieve better results
than either ZnCl2 or K10 alone (entries 6 and 7). In the present pro-
cedure, the supported catalyst could be reused one or two time
without significant decrease in activity after being washed with
dichloromethane and activated at 120 °C for 4 h, the yield of 1,3-di-
phenyl-3-hydroxy-2-(1H-indol-3-yl)-1-propanone was 85% and
82%, respectively (Table 1, entries 8 and 9).
Table 1
The effect of the amount of supported catalyst on the reaction of indole and 2,3-
epoxyl-1,3-diphenyl-1-propanone (1a) under ultrasound at room temperature.
Entry
Amount of catalyst (mg)
Time (h)
Isolated yield (%)
1
2
3
4
5
6
7
8
9
385
288
193
96
2
2
2
2
81
83
90
78
0
2
No reaction
193
193
193
193
2a
2b
2c
2d
19
88
85
82
a
b
c
193 mg K10 used only.
193 mg ZnCl2 used only.
K10-ZnCl2 recycled one time.
K10-ZnCl2 recycled two times.
In order to verify the effect of ultrasound irradiation, the reac-
tion was also performed in silent condition at room temperature.
d

J.-T. Li et al. / Ultrasonics Sonochemistry 17 (2010) 359–362
361
Table 2
The reaction of 3-aryl-2,3-epoxyl-1-phenyl-1-propanone and indole under ultrasound irradiation at room temperature.
Entry
Ar
Time (h) (Stira)
Product
Isolated yield (%) (Stira)
M.p. (°C)
a
b
c
d
e
f
g
h
i
C6H5
2 (10)
3
4
2 (11.5)
2
4
2
2a
2b
2c
2d
2e
2f
2g
2h
2i
90 (84)
77
69
92 (87)
93
80
81
90
76
66 (55)
99–101
79–80
3-NO2C6H4
4-CH3C6H4
3-ClC6H4
120–122
176–178
150–152
99–101
188–190
148–150
204–206
112–114
4-ClC6H4
4-NO2C6H4
3-BrC6H4
3,4-Cl2C6H3
2-NO2C6H4
2-CH3OC6H3
2
5
j
4.5 (12.5)
2j
a
Stirring alone without ultrasound irradiation at room temperature.
As shown in Table 2 and 1,3-diphenyl-3-hydroxy-2-(1H-indol-3-
yl)-1-propanone (2a) was obtained in 84% yield for 10 h by stirring
alone, while under sonication, 2a was obtained in 90% yield within
2 h (Table 2, entry a). The yield of 2d was 87% by stirring for 11.5 h,
whereas under ultrasound irradiation 2d was obtained in 92% yield
within 2 h (Table 2, entry d). The synthesis of b-indoyl alcohol 2j
was carried out in 55% yield within 12.5 h by stirring only, while
under the ultrasonication, the reaction was completed in 4.5 h to
give 2j in 66% yield (Table 2, entry j). It is apparent that the ultra-
sound can accelerate this reaction significantly, the reaction can be
finished in shorter time under ultrasound.
From the results above, the optimum reaction conditions were
chosen: indole (1 mmol), 3-aryl-2,3-epoxyl-1-phenyl-1-propanone
(1, 1 mmol), K10-ZnCl2 (0.5 mmol, 193 mg) and dichloromethane
(5 mL). Under this reaction condition, a series of experiments for
the synthesis of 3-aryl-3-hydroxy-2-(1H-indol-3-yl)-1-phenyl-1-
propanone were carried out under ultrasound irradiation at room
temperature. The results were summarized in Table 2.
sequent decrease in particle size and increase in surface area
available for reaction [20]. All of these can cause the reaction to
take place rapidly.
4. Conclusion
In conclusion, we have found an efficient and practical proce-
dure for the preparation of 3-aryl-3-hydroxy-2-(1H-indol-3-yl)-1-
phenyl-1-propanone from 3-aryl-2,3-epoxyl-1-phenyl-1-propa-
none and indole under ultrasound irradiation at room temperature
in the present of montmorillonite K10-ZnCl2. The present proce-
dure has many advantages such as short reaction time, mild condi-
tions and easy operation procedures.
Acknowledgements
We thank the Natural Science Foundation of Hebei Province
(B2006000969), China, for financial support.
As shown in Table 2, the synthesis of 3-aryl-3-hydroxy-2-(1H-
indol-3-yl)-1-phenyl-1-propanone via the addition of indole to 3-
aryl-2,3-epoxyl-1-phenyl-1-propanone was carried out in good
yields catalyzed by K10-ZnCl2 under ultrasound irradiation. From
the data in Table 2, it seems that the epoxychalcones containing
electron-withdrawing groups were found to be more reactive
(2d, 2e and 2h). In contrast, the epoxychalcones containing elec-
tron-donating group have shown lower reactivity (2c and 2j). This
shows that the electronic effects of substituents have a significant
effect on the reaction. Steric factors also have a role to play in the
reactivity of epoxychalcones. Ring-opening occurred exclusively at
the less hindered carbon of the epoxy-bond. For example, the ring-
opening reaction of 1f with indole was completed in 4 h in 80%
yield, while the reaction between 1i with indole was finished in
5 h in 76% yield.
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