A facile synthesis of α,α′-bis(substituted benzylidene) cycloalkanones catalyzed by KF/Al2O3 under ultrasound irradiation

Article abstract of DOI:10.1081/SCC-120021982

The condensation of the cyclopentanone or cyclohexanone with aromatic aldehydes catalyzed by KF/Al₂O₃ in MeOH under ultrasound irradiation, result the corresponding 2,5-bis(substituted benzylidene) cyclopentanones or 2,6-bis(substituted benzylidene) cyclohexanones in good yields.

Full text of DOI:10.1081/SCC-120021982

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A Facile Synthesis of α,α′-bis(Substituted Benzylidene)
Cycloalkanones Catalyzed by KF/Al2O3 Under
Ultrasound Irradiation
Ji-Tai Li a , Wen-Zhi Yang a , Guo-Feng Chen a & Tong-Shuang Li a
a College of Chemistry and Environmental Science , Hebei University , Baoding, P.R. China
Published online: 17 Aug 2006.
To cite this article: Ji-Tai Li , Wen-Zhi Yang , Guo-Feng Chen & Tong-Shuang Li (2003) A Facile Synthesis of α,α′-
bis(Substituted Benzylidene) Cycloalkanones Catalyzed by KF/Al2O3 Under Ultrasound Irradiation, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 33:15, 2619-2625, DOI: 10.1081/
SCC-120021982
To link to this article: http://dx.doi.org/10.1081/SCC-120021982
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 15, pp. 2619–2625, 2003
A Facile Synthesis of a,a0-bis(Substituted
Benzylidene) Cycloalkanones Catalyzed by
KF/Al2O3 Under Ultrasound Irradiation
*
Ji-Tai Li, Wen-Zhi Yang, Guo-Feng Chen,
and Tong-Shuang Li
College of Chemistry and Environmental Science,
Hebei University, Baoding, P.R. China
ABSTRACT
The condensation of the cyclopentanone or cyclohexanone with
aromatic aldehydes catalyzed by KF/Al2O3 in MeOH under
ultrasound irradiation, result the corresponding 2,5-bis(substituted
benzylidene) cyclopentanones or 2,6-bis(substituted benzylidene)
cyclohexanones in good yields.
Key Words: bis(Substituted benzylidene) cycloalkanone; Claisen-
Schmidt condensation; Ultrasound; Supported catalyst.
*Correspondence: Ji-Tai Li, College of Chemistry and Environmental Science,
Hebei University, No. 88, Hezuo Road, Baoding 071002, P.R. China;
E-mail: orgsyn@mail.hbu.edu.cn.
2619
DOI: 10.1081/SCC-120021982
Copyright & 2003 by Marcel Dekker, Inc.
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2620
Li et al.
The a,a0-bis(substituted benzylidene) cycloalkanones are used as
precursors to potentially bioactive pyrimidine derivatives,[1] intermediates
of agrochemical, pharmaceuticals, and perfumes.[2] Preparation of
a,a0-bis(substituted benzylidene) cycloalkanones is usually completed via
Claisen-Schmidt condensation between cycloalkanones and aromatic
aldehydes catalyzed by solid NaOH[3–6] or NaOEt,[7] using conven-
tional heating method. It also has been reported that some compounds,
such as bis(p-ethoxyphenyl)telluroxide (BMPTO),[8] RuCl3,[9] SmI3,[10]
Cp2ZrH2,[11] TiCl3(SO3CF3),[12] were used as catalysts. But there were
some shortcomings in terms of high cost, difficult preparation, and
especially reaction conditions.
Ultrasound has been used more and more frequently in organic
synthesis in recent three decades. Compared with traditional methods,
this method is more convenient and easily controlled. Great many of
organic reactions can be carried in higher yields, shorter reaction time
or milder conditions under ultrasound irradiation. Our laboratory has
reported the Claisen-Schmidt condensation of acetophenone with various
aromatic aldehydes catalyzed by KF/Al2O3 under ultrasound irradiation,
and the result are better than that under conventional heating condition.[13]
In connection with our on going work on KF/Al2O3—catalysis under
ultrasound, herein we wish to report the condensation of cycloalkanones
with aromatic aldehydes catalyzed by KF/Al2O3 in MeOH under ultra-
sound irradiation.
As reported previously, Claisen-Schmidt condensation of aceto-
phenone with aromatic aldehydes catalyzed by KF/Al2O3, the best
molar ratio of the catalyst to substrate is 0.8–1.[13] In this article, the
molar ratio of catalyst to cycloalkanone was 1:1. As shown in Table 1
and Sch. 1, the condensation of cyclopentanone or cyclohexanone with a
variety of aromatic aldehydes afforded a,a0-bis(substituted benzylidene)
cycloalkanones in good yields catalyzed by KF/Al2O3 in MeOH at
30–40ꢀC for 0.5–2.5 h under ultrasound irradiation. Meanwhile, we
observed that KF/Al2O3 acted as an efficient catalyst for cross-aldol
condensation reaction of cycloalkanones with aromatic aldehydes
without occurrence of any self-condensation of ketones. In the classical
condensation of aromatic aldehydes and cycloalkanones catalyzed by
NaOH (aq) in 95% EtOH, compounds 3a, 3c, 3d, 3h, and 3i were obtained
with 60–90, 60–90, 60–90, 30–50, and 40–60% yields.[6] While, the present
method gave 3a, 3c, 3d, 3h, and 3i in 89, 92, 87, 80, and 73% yields
respectively. The condensation of cyclopentanone (1) with furfural (2e)
gave 96% yield (3e) catalyzed by KF/Al2O3 in 30 min under ultrasound
irradiation, and the yield (3e) is higher than that obtained 85% yield
catalyzed by KOH in 30 min under ultrasound.[5]

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a,a0-bis(Substituted Benzylidene) Cycloalkanones
2621
Scheme 1.
Table 1.
Entry
n ¼ 0, Ar
C6H5-
Entry
n ¼ 1, Ar
C6H5–
a
b
c
f
g
h
i
p-O2NC6H4–
p-H3COC6H4–
C6H5CH¼CH–
Furyl
p-O2NC6H4–
p-H3COC6H4–
C6H5CH¼CH–
Furyl
d
e
j
To test the selectivity of the reaction, we carried out the reaction in
ratio (furural/cyclohexanone) of 2:1 and 1:1 (Entry 1jc). Both the reaction
provided the same product a,a0-bis(fururylidene) cyclohexanone (3j),
a-(fururylidene) cyclohexanone was not obtained. Fromthese results
we can deduce that the yields are, in general, similar or higher than
these describe in the Lit.[5,6,8,11] We also did the experiment catalyzed by
KF/Al2O3 in the absence of ultrasound, the condensation of cyclohexa-
none (1) with furural (2j) was carried out in 87% (3jd) yield using stirring.
Compared with literature reported, the main advantages of the present
procedure are minimally environmental pollution, cheap, and reusable
catalyst,[13] easier work-up, milder conditions, better yields, and shorter
reaction time.
As shown in Sch. 2, a potential mechanism could account for the
formation of a,a0-bis(substituted benzylidene) cycloalkanones: the surface
of alumina coated with potassium fluoride provides a strong polar
environment, which is favorable to many ionic and heterolytic reactions.
EXPERIMENTAL
Liquid aldehydes were purified by distillation prior to use. Melting
points were uncorrected. Infrared spectra were recorded on a Bio-Rad
1
FTS-40 spectrometer (KBr). H NMR spectra were measured on VXR-
300S (300 MHz) or Bruker AM-400S (400 MHz) spectrometer using TMS
as internal standard and CDCl3 as solvent. Mass spectra were determined

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2622
Li et al.
Scheme 2.
on a VG-7070E spectrometer (EI, 70 eV). Sonication was performed in a
Shanghai Branson-CQX ultrasonic cleaner with a frequency of 25 kHz and
a nominal power 500 W. The reaction flask was located in the maximum
energy area in the cleaner, and the addition or removal of water controlled
the temperature of the water bath.
Preparation of the Catalyst (KF-Al2O3)
The KF-Al2O3 was prepared by dissolving 20 g of KF in 80 mL of
water and 30 g of neutral Al2O3. The mixture was stirred at 65–75ꢀC for
1 h. The water was removed under reduced pressure. The resulting free
flowing powder was dried at 120ꢀC for 4 h. The content of KF is about
30% (150 mg mixture/mmol KF).
General Procedure
A Pyrex flask (50 mL) was added aromatic aldehyde (1, 2 mmol),
cycloalkanone (2, 1 mmol), MeOH (2 mL), and KF-Al2O3 (150 mg). The
mixture was irradiated in the water bath of an ultrasonic cleaner at the
temperature for the period as indicated in Table 2 (Sonication was

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a,a0-bis(Substituted Benzylidene) Cycloalkanones
2623
continued until crystals were appeared or aldehyde was disappeared
indicated by TLC). The mixture was dissolved in CH2Cl2. The catalyst
was removed by filtration and washed with CH2Cl2. The solvent was
evaporated under reduced pressure and the residue was crystallized
with dichloromethane/ethanol to give a,a0-bis(substituted benzylidene)
cycloalkanones or the residue chromatographed on a column of silica
gel using light petroleum(b.p. 60–90 ꢀC)/dichloromethane as eluent.
The authenticity of the products was established by comparing their
1
melting points with literature and the data of IR, MS, and H NMR
spectra.
Table 2. Preparation of a,a0-bis(substituted benzylidene) cycloalkanones
catalyzed by KF/Al2O3 in MeOH under ultrasound irradiation.
Time (min)/
Entry Mole ratioa temperature (ꢀC)
Product yieldb (%),
(reported)
M.p. (ꢀC)
(reported)
a
b
c
d
e
f
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
40/30–35
60/35–40
120/35–40
60/35–40
30/35–40
60/35–40
150/35–40
150/35–40
150/35–40
30/35–40
89
(84.5),[8] (69),[11] (60–90)[6]
66
195–196
(188.5)[9]
253–254
(230–231)[8]
220–221
(210–211)[8]
224–225
(223)[9]
(81)[8]
92
(53.5),[8] (60–90)[6]
87
(93.4),[8] (71),[11] (60–90)[6]
96
170–171
(165)[8]
115–117
(77.5),[8] (67),[11] (85)[5]
62
(64.5),[8] (70),[11] (50–80)[6] (116–117)[9]
g
h
i
60
(71.4)[8]
208–210
(159)[8]
80
(69.5),[8] (30–50)[6]
73
160–162
(203–204)[8]
188–189
(71),[8] (84),[11] (40–60)[6] (179–180)[8]
j
94
(86)[8,11]
93c
87d
145–146
(145)[8]
1:1
2:1
30/35–40
150/40
aThe mole ratio is aldehyde/cycloalkanone.
bIsolated yield based on aromatic aldehydes.
cThe ratio of furural to cyclohexanone is 1:1.
dThe reaction was carried out using magnetic stirrer catalyzed by KF/Al2O3
without ultrasound irradiation.

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2624
3b. Yellow platelets fromdichloromethane/ethanol.
Li et al.
ꢀmax (KBr):
3080, 1680, 1610, 1520, 1350, 1260, 1190, 870, 820, 770 cmÀ1. ꢁH
(400 MHz): 3.22 (4H, m, –CH2-CH2–), 7.67 (2H, s, ¼CH–), 7.76
(4H, d, J ¼ 8.0 Hz, Hb), 8.33 (4H, d, J ¼ 8.0 Hz, Ha ) ppm. m/z (%): 350
(Mþ, 15), 304 (15), 303 (46), 228 (13), 126 (43), 115 (100), 77 (32), 51 (15),
40 (96).
3c. Yellow platelets fromethanol. ꢀmax (KBr): 3080, 2850, 1680,
1590, 1490, 1430, 1400, 1370, 1300, 1245, 1190, 1023, 923, 830 cmÀ1. ꢁH
(400 MHz): 3.10 (4H, m, –CH2-CH2–), 3.88 (6H, s, –OCH3), 6.98 (4H, d,
J ¼ 8.0 Hz, Ha), 7.58 (2H, s, ¼CH–), 7.59 (4H, d, J ¼ 8.0 Hz, Hb) ppm.
m/z (%): 320 (Mþ, 60), 305 (10), 289 (23), 160 (25), 146 (50), 131 (48), 121
(63), 115 (34), 103 (75), 91 (30), 77 (31), 40 (100).
3g. Yellow platelets fromdichloromethane/ethanol.
ꢀmax (KBr):
3100, 1680, 1590, 1520, 1490, 1350, 860, 810 cmÀ1. ꢁH (300 MHz): 1.86
(2H, m, –CH2CH2CH2–), 2.95 (4H, m, –CH2CH2CH2–), 7.60 (4H, d,
J ¼ 8.7, Hb), 7.80 (2H, s, ¼CH–), 8.28 (4H, d, J ¼ 8.7 Hz, Ha ) ppm.
m/z (%): 364 (Mþ, 6), 348 (30), 318 (15), 290 (19), 245 (11), 216 (28),
168 (19), 153 (20), 128 (50), 115 (71), 103 (42), 91 (29), 77 (45), 65 (80), 55
(8), 51 (23), 40 (100).
3h. Yellow needles fromethanol. ꢀmax (KBr): 2850, 1670, 1590, 1240,
1150–1101, 1018, 930, 828 cmÀ1
. ꢁH (300 MHz): 1.76 (2H, m,
–CH2CH2CH2–), 2.94 (4H, m, –CH2CH2CH2–), 3.86 (6H, s, –OCH3),
6.95 (4H, d, J ¼ 8.7, Ha), 7.47 (4H, d, J ¼ 8.7 Hz, Hb), 7.78 (2H, s,
¼CH–) ppm. m/z (%): 334 (Mþ, 19), 306 (15), 270 (11), 200 (11), 172
(11), 160 (15), 147 (62), 131 (47), 121 (55), 115 (40), 103 (100), 91 (38), 77
(38), 55 (9), 40 (15).
3i. Yellow platelets fromdichloromethane/ethanol.
ꢀmax (KBr):
3050, 2890, 1605, 1590, 1580, 1455, 1295, 1240, 1160, 990–910, 750,
700 cmÀ1. ꢁH (400 MHz): 1.91 (2H, m, –CH2CH2CH2–), 2.83 (4H,
m , –HC2CH2CH2–), 7.00 (2H, d, J ¼ 15.6, ¼CH-CH¼CH–), 7.10
(2H, dd, J ¼ 15.6, 11.2, ¼CH-CH¼CH–), 7.32 (2H, t, J ¼ 7.2, Hc), 7.38
(4H, dd, J ¼ 7.6,7.2, Ha), 7.50 (2H, d, J ¼ 11.2, ¼CH-CH¼CH–),
7.52 (4H, d, J ¼ 7.6, Hb) ppm. m/z (%): 326 (Mþ, 38), 249 (9),
235 (30), 178 (21), 165 (13), 141 (32), 128 (32), 115 (53), 91 (100),
77 (17), 65 (11), 40 (68).
ACKNOWLEDGMENT
NSFC (29872011) and NSF of Hebei Province supported the project
(203107).

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a,a0-bis(Substituted Benzylidene) Cycloalkanones
2625
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Received in Japan September 21, 2002

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