A convenient synthesis of α,α'-bis(substituted benzylidene)cycloalkanones Catalyzed by Y(TFA) 3

Article abstract of DOI:10.1080/15533174.2011.613882

Aromatic aldehydes undergo crossed aldol condensation with cyclic ketones in the presence of Y(TFA)₃ under solvent-free conditions to afford the corresponding α,α-bis(substituted benzylidene)cycloalkanones in satisfactory yields. Furthermore, the catalyst can be recovered conveniently and reused several times in the reaction with comparable yields. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/15533174.2011.613882

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A Convenient Synthesis of α,α’-Bis(substituted
benzylidene)cycloalkanones Catalyzed by Y(TFA)3
Genxiang Luo a , Runxia Wang a & Chunsheng Liu a
a Department of Chemistry, School of Chemistry and Materials Science, Liaoning Shihua
University, Fushun, Liaoning, P. R. China
Accepted author version posted online: 14 Mar 2012.Published online: 01 May 2012.
To cite this article: Genxiang Luo , Runxia Wang & Chunsheng Liu (2012): A Convenient Synthesis of α,α’-Bis(substituted
benzylidene)cycloalkanones Catalyzed by Y(TFA)3 , Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal
Chemistry, 42:4, 554-556
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Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry, 42:554–556, 2012
Copyright ꢀ Taylor & Francis Group, LLC
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ISSN: 1553-3174 print / 1553-3182 online
DOI: 10.1080/15533174.2011.613882
A Convenient Synthesis of ␣,␣’-Bis(substituted
benzylidene)cycloalkanones Catalyzed by Y(TFA)3
Genxiang Luo, Runxia Wang, and Chunsheng Liu
Department of Chemistry, School of Chemistry and Materials Science, Liaoning Shihua University,
Fushun, Liaoning, P. R. China
reaction time, side reactions, low yields, and hazardous and of-
ten expensive acid catalysts. Thus, it is significant to exploit new
and efficient catalysts for the synthesis of α,α’-bis(substituted
benzylidene)cycloalkanones.
Aromatic aldehydes undergo crossed aldol condensation with
cyclic ketones in the presence of Y(TFA)3 under solvent-free con-
ditions to afford the corresponding α,α’-bis(substituted benzyli-
dene)cycloalkanones in satisfactory yields. Furthermore, the cata-
lyst can be recovered conveniently and reused several times in the
reaction with comparable yields.
In recent times, the use of trifluoroacetates has received
considerable attention as an inexpensive, non-toxic, and read-
ily available Lewis acids catalyst for various organic trans-
formations. Trifluoroacetates with some kinds of metals were
first reported by Swarts in 1939.[18] Trifluoroacetates such as
Fe(TFA)3[19,20] and Bi(TFA)3[21] were utilized as powerful cata-
lysts to synthesize multifarious compounds. Our research group
has successfully synthesized 3,4-dihydropyrimidin-2(1H)-ones
and α,α’-bis(substituted benzylidene)cycloalkanones catalyzed
by Cu(TFA)2 in high yields and short reaction time under
solvent-free conditions.[22,23]
As a continuation of our interest in the development of
efficient and simple procedures for the synthesis of α,α’-
bis(substituted benzylidene)cycloalkanones, we report Y(TFA)3
as potential Lewis acid catalysts for the synthesis of α,α’-
bis(substituted benzylidene)cycloalkanones via solvent-free
conditions (Scheme 1).
Keywords α,α’-bis(substituted benzylidene)cycloalkanones, cross-
aldol condensation, solvent-free conditions, yttrium(III)
trifluoroacetate
INTRODUCTION
The α,α’-bis(substituted benzylidene)cycloalkanones are
very important intermediates of agrochemical pharmaceuti-
cals,[1] important precursors of potentially bioactive pyrimidine
derivates,[2] new organic material for non-linear optical applica-
tions,[3] cytotoxic analogous,[4] and the units of liquid-crystalline
polymers.[5] Cross-aldol condensation is available for this syn-
thesis and is classically carried out using strong acid or base.
However, this process suffers from reverse and side reactions
resulting in low yields of the products. So the synthesis of α,α’-
bis(substituted benzylidene)cycloalkanones has received more
attention and many improved procedures have been reported
to increase the efficiency of cross-aldol condensation. Several
metal(II) ions, such as Mn(II), Fe(II), Co(II), Ni(II), Cu(II), and
Zn(II), were used as catalysts.[6] A lot of other reagents such
as, I2,[2] RuCl3,[7] SmI3,[8] LiClO4,[9] TiCl4•2THF,[10] TCT,[11]
FeCl3,[12] InCl3,[13] silica sulfuric acid,[14] and Mg(HSO4)2
[15]
have also been used to catalyze the cross-aldol condensation
reaction. In addition, microwave irradiation[16] and high pres-
sure[17] were employed to improve yields as well as reduce re-
action time. However, some of the methods suffered from long
SCH. 1.
EXPERIMENTAL
Melting points were measured on X-6 microscope melting
points apparatus and uncorrected. IR spectra were measured
on Spectrum GX spectrometer (KBr). H NMR spectra were
recorded on Bruker AVANCE 600 spectrometer (600 MHz for
1H NMR; Madison, WI, USA), using CDCl3 as solvent and
tetramethylsilane (TMS) as internal reference.
1
Received 28 September 2010; accepted 9 August 2011.
Address correspondence to Genxiang Luo, Department of Chem-
istry, School of Chemistry and Materials Science, Liaoning Shihua
University, Fushun, Liaoning 113001, P. R. China. E-mail: genxian-
gluo@yahoo.com.cn
554

Y(TFA)3 CATALYSES ALDOL CONDENSATIONS
555
TABLE 1
General Procedure for Preparation of Yttrium(III)
Trifluoroacetate
Yttrium(III) trifluoroacetate was prepared according to the
reported procedure.[24] Excessive Y2O3 was reacted with the
trifluoroacetic acid. After complete reaction, the mixture was
filtered, and then the filtrate was evaporated to dryness on water
bath. The product of Y(TFA)3 was recrystallized twice.
Synthesis of α,α’-Bis(substituted benzylidene)cycloalkanones
catalyzed by Y(TFA)3 under solvent-free conditions at 90
M.p. (◦C)
Entry
Ar
n Yielda (%) Found
Reported
3a
3b
3c
3d
3e
3f
3g
3h
3i
CC6H5
1
1
1
1
83
96
94
81
98
81
92
92
87
98
94
98
83
98
80
96
187–190 189–190[2]
228–230 228–229[2]
208–210 206–207[2]
Cp-ClC6H4
C2,4-(Cl) 2-C6H3
Cp-HOC6H4
General Procedure for Preparation of ␣,␣’-Bis(substituted
benzylidene)cycloalkanones
>300
>300[2]
A mixture of benzaldehyde (20 mmol), cyclohexanone (12
mmol), and Y(TFA)3 (2 mmol) was heated at 90◦C for 7 h in
water bath. After completion of the reaction as notice by TLC,
the reaction was diluted with10 mL alcohol and 15 mL deionized
water, and the contents were stirred for 10 min. The solid was
filtered under suction, washed with ice-cold water, and dried to
afford pure product 2.4 g in 87% yield.
CC6H5CH = CH 1
214–216 215–216[2]
213–214 211–212[2]
244–245 243–244[2]
155–156 159–167[2]
114–115 116–117[7]
198–199 200–202[1]
144–146 147–148[7]
160–162 163–164[2]
296–298 290–292[2]
178–180 177–178[2]
156–158 159–160[9]
163–165 164–165[2]
Cp-MeOC6H4
Cp-MeC6H4
C2-ClC6H4
1
1
1
2
2
2
2
2
CC6H5
3j
3k
3l
Cm-NO2C6H4
Cp-ClC6H4
C2,4-(Cl) 2-C6H3
All products are known compounds, which were satisfacto-
rily characterized by physical and spectra data.
3m Cp-HOC6H4
Selected spectral data are as follows:
3n
3o
3p
CC6H5CH = CH 2
α,αꢀ-Bis (4-chlorobenzylidene) cyclopentanone (3b). M.p.:
Cp-MeOC6H4
Cp-MeC6H4
2
2
228–230◦C; IR (KBr): 2911, 1687, 1622, 1603, 1589
cm−1 1H NMR (600 MHz, CDCl3, TMS): δ(ppm)
;
aIsolated yield.
7.54–7.43 (m, 6H), 7.40–7.27 (m, 4H), 3.11 (s, 4H).
α,αꢀ-Bis(2,4-dichlorobenzylidene)cyclopentanone (3c). M.p.:
208–210◦C; IR (KBr): ν = 3071, 2910, 1694, 1622,
1459 cm−1; 1H NMR (600 MHz, CDCl3, TMS): δ(ppm)
7.86 (s, 2H), 7.50–7.27 (m, 6H), 2.99 (s, 4H).
The reaction was carried out at different reaction temperatures
(70, 80, 90, and 100◦C), different reaction time (3, 5, 7, and 8
h) and different dosages of catalyst (4–12 mol%). Through in-
vestigation, optimized conditions were obtained by carrying out
the reaction with 2:1.2 mole ratios of benzaldehyde to cyclohex-
anone at 90◦C and the dosage of 10 mol% catalyst for 7 h under
solvent-free conditions. Based on the optimum reaction condi-
tions, the reactions of various aldehydes with cyclohexanone
or cyclopentanone were investigated. The results are shown in
Table 1.
In the course of the study, the reactions proceeded com-
pletely to afford the corresponding α,α’-bis(substituted ben-
zylidene)cycloalkanone derivatives. We observed that Y(TFA)3
can act as a very excellent catalyst for cross-aldol condensation
reaction of cycloalkanones with aromatic aldehydes without
appearance of any self-condensation. It seems that the effect of
substituted groups on the aromatic aldehydes is not very strong,
and both the electron-donating and electron-withdrawing groups
worked well. Furthermore, both cyclopentanone and cyclohex-
anone showed the similar activity toward the crossed aldol con-
densation reaction with excellent yields.
α,αꢀ-Bis(4-methylbenzylidene)cyclopentanone (3g). M.p.:
244–245◦C; IR (KBr): ν = 2913, 1694, 1622, 1608,
1585 cm−1; 1H NMR (600 MHz, CDCl3, TMS): δ(ppm)
7.50–7.59 (m, 6H), 7.25–7.27 (m, 4H), 3.12 (s, 4H),
2.41 (s, 6H).
α,αꢀ-Bis (m-nitrobenzylidene)cyclohexanone (3j). M.p.:
198–199◦C; I.R. (KBr): 3082, 2954, 1663, 1604, 1522
cm−1; 1H NMR (600 MHz, CDCl3, TMS): δ(ppm) 8.33
(s, 2H), 8.21 (d, 2H), 7.82 (t, 2H), 7.62 (t, 2H), 7.27 (s,
2H), 2.98 (t, 4H), 1.90–1.86 (m, 2H).
α,αꢀ-Bis (2,4-dichlorobenzylidene) cyclohextanone (3l).
M.p.: 160–162◦C; I.R. (KBr): 3096, 2970, 1660, 1598,
1
1578, 1464, 1140 cm−1; H NMR (600 MHz, CDCl3,
TMS): δ(ppm) 7.82 (s, 2H), 7.47 (s, 2H), 7.27 (s, 4H),
2.75 (t, 4H), 1.79–1.77 (m, 2H).
α,αꢀ-Bis (4-Methoxybenzylidene)cyclohexanone (3o). M.p.:
156–158◦C; I.R. (KBr): 2938, 1658, 1594, 1555, 1508,
1
1249, 1024, 836cm−1; H NMR (600 MHz, CDCl3,
TMS): δ(ppm) 7.77 (s, 2H), 7.48–6.93 (m, 8H), 3.86
(s, 6H), 2.94 (t, 4H), 1.83–1.79 (m, 2H).
A comparison of our results with those reported in the lit-
erature clearly shows the advantage of Y(TFA)3 as catalyst
(Table 2). The main advantages of our method are clean and
environmentally benign reagents with ease of separation of the
RESULTS AND DISCUSSIONS
Initially, the reaction of benzaldehyde and cyclohexanone product and reagents.
was chosen as the model reaction to detect the catalytic capa-
The recyclable character of Y(TFA)3 was also investigated.
bility of Y(TFA)3 and to investigate the optimized conditions. Y(TFA)3 was very easy to recover by simple extraction from

556
G. LUO ET AL.
8. Li, Z.; Zhang, Y.; Li, Q. Samarium (III) iodide promoted preparation of
TABLE 2
α,α’-bis (substituted benzylidene)cyclohexanones from benzaldehydes and
cyclohexanone. J. Chem. Res. 2000, 2000, 580–581.
9. Abaee, M.S.; Mojtahedi, M.M.; Sharifi, R.; Zahedi, M.M.; Abbasi, H.;
Tabar-Heidar, K. Facile synthesis of bis(arylmethylidene) cycloalkanones
mediated by lithium perchlorate under solvent-free conditions. J. Iran.
Chem. Soc. 2006, 3, 293–296.
Comparison of results using Y(TFA)3 with those obtained by
other workers for the synthesis of α,α’-bis(substituted
benzylidene)cycloalkanones
Conditions
T (◦C)
Time (h)
Yield (%)
Ref.
10. Tao, X.C.; Liu, R.Z.; Meng, Q.H.; Zhao, Y.Y.; Zhou, J.L.; Huang, Y.B. The
reaction of ketones with benzaldehyde catalyzed by TiCl4·2THF. J. Mol.
Catal. A: Chem. 2005, 225, 239–243.
11. Bigdeli, M.A.; Mahdavinia, G.H.; Jafari, S.; Hazarkhani, H. Wet 2,4,6-
trichloro[1,3,5]triazine (TCT) an efficient catalyst for synthesis of α,αꢀ-
bis(substituted-benzylidene) cycloalkanones under solvent-free conditions.
Catal. Commun. 2007, 8, 2229–2231.
Y(TFA)3
Yb(OTf)3
TCT
Silica sulfuric acid
Mg(HSO4)2
90
90
90
80
60
7
6
0.33
2.5
8
96
94
92
94
82
—
[2]
[11]
[14]
[15]
12. Zhang, X.Y.; Fan, X.S.; Niu, H.Y.; Wang, J.J. An ionic liquid as a re-
cyclable medium for the green preparation of α,αꢀ-bis (substituted ben-
zylidene)cycloalkanones catalyzed by FeCl3·6H2O. Green Chem. 2003, 5,
267–269.
13. Deng, G.S.; Ren, T.G. Indium trichloride catalyzes aldol-condensations of
aldehydes and ketones. Synth. Commun. 2003, 33, 2995–3001.
14. Salehi, P.; Dabiri, M.; Zolfigol, M.A.; Fard, M.A. B. Silica sulfuric acid as
an efficient and reusable reagent for crossed-aldol condensation of ketones
with aromatic aldehydes under solvent-free conditions. J. Braz. Chem. Soc.
2004, 15, 773–776.
15. Salehi, P.; Khodaei, M.M.; Zolfigol, M.A.; Keyvan, A. Solvent-free crossed
aldol condensation of ketones with aromatic aldehydes mediated by mag-
nesium hydrogensulfate. Monatsh. Chem. 2002, 133, 1291–1295.
16. Esmaeili, A.A.; Tabas, M.S.; Nasseri, M.A.; Kazemi, F. Solvent-free
crossed aldol condensation of cyclic ketones with aromatic aldehydes as-
sisted by microwave irradiation. Monatsh. Chem. 2005, 136, 571–576.
17. Sekiguchi, Y.; Sasaoka, A.; Shimomoto, Fujioka, A.S.; Kotsuki, H. High-
pressure-promoted asymmetric aldol reactions of ketones with aldehydes
catalyzed by l-proline. Synlett 2003, 2003, 1655–1658.
the reaction medium. It was reused in subsequent reactions and
the yields of α,α’-bis(substituted benzylidene)cyclohexanone
were 80%, 77%, 73%, and 69% in consecutive model reactions
respectively. In view of the previous results, Y(TFA)3 is an
efficient and reusable catalyst to synthesize α,α’-bis(substituted
benzylidene)cycloalkanones.
In summary, Y(TFA)3 was found to be an excellent and
reusable catalyst in the crossed aldol condensations of aromatic
aldehydes with cyclic ketones to afford the α,α’-bis(substituted
benzylidene)cycloalkanones under solvent-free conditions. The
mild conditions, short reaction time, inexpensive and recyclable
character of the catalyst, and a simpler experimental procedure
are the great advantages of the method.
18. Krupoder, S.A.; Danilovich, V.S.; Miller, A.O.; Furin, G.G. Polyfluoro-
carboxylates. I. Copper(II) trifluoroacetate and its analogues. J. Fluorine
Chem. 1995, 73, 13–15.
19. Adibi, H.; Samimi, H.A.; Beygzadeh, M. Iron(III) trifluoroacetate and
trifluoromethanesulfonate: Recyclable Lewis acid catalysts for one-pot
synthesis of 3,4-dihydropyrimidinones or their sulfur analogues and 1,4-
dihydropyridines via solvent-free Biginelli and Hantzsch condensation pro-
tocols. Catal. Comm. 2007, 8, 2119–2124.
REFERENCES
1. Das, B.; Thirupathi, P.; Mahender, I.; Reddy, K.R. Convenient and facile
cross-Aldol condensation catalyzed by molecular iodine: An efficient syn-
thesis of α,αꢀ-bis(substituted-benzylidene) cycloalkanones. J. Mol. Catal.
A: Chem. 2006, 247, 182–185.
2. Wang, L.M.; Sheng, J.; Tian, H.; Han, J.W.; Fan, Z.Y.; Qian, C.T. A con-
venient synthesis of α,αꢀ-bis(substituted benzylidene)cycloalkanones cat-
alyzed by Yb(OTf)3 under solvent-free conditions. Synthesis 2004, 2004, 20. Adibi, H.; Jafari, H. Facile protection of carbonyl compounds as oxathi-
3060–3064.
olanes and transoxathioacetalization of oxyacetals promoted by iron(III)
trifluoroacetate or trifluoromethanesulfonate as chemoselective and recy-
clable catalysts. J. Fluorine Chem. 2007, 128, 679–682.
3. Kawamata, J.; Inoue, K.; Inabe, T.; Kiguchi, M.; Kato M.; Taniguchi,
Y. Large second-harmonic generation coefficients of bis(benzylidine) cy-
cloalkanones estimated by the second-harmonic wave generated with the 21. Khosropour, A.R.; Mohammadpoor-Baltork, I.; Ghorbankhani, H.
evanescent wave technique. Chem. Phys. Lett. 1996, 249, 29–34.
4. Dimmock, J.R. A.; Padmanilayam, M.P.; Zello, G.A.; Nienaber, K.H.;
Allen, T.M.; Santos, C.L.; de Clercq, E.; Balzarini, J.; Manavathu, E.K.;
Bi(TFA)3 immobilized in [nbpy]FeCl4: An efficient catalyst system for the
one-pot synthesis of 4,6-diarylpyrimidin-2(1H)-ones. Catal. Comm. 2006,
7, 713–716.
Stables, J.P. Cytotoxic analogues of 2,6-bis(arylidene)cyclohexanones. Eur. 22. Song, D.L.; Wang, R.X.; Chen, Y.L.; Zhang, S.H.; Liu, C.S.; Luo, G.
J. Med. Chem. 2003, 38, 169–177.
Copper(II) trifluoroacetate catalyzed synthesis of 3,4-dihydropyrimidin-
2(1H)-ones. React. Kinet. Catal. Lett. 2008, 95, 385–390.
5. Gangadhara, K.K. Synthesis and characterization of photo-crosslinkable
main-chain liquid-crystalline polymers containing bis(benzylidene)
cycloalkanone units. Polymer 1995, 36, 1903–1910.
6. Irie, K.; Watanabe, K. Aldol condensations with metal(II) complex cata-
lysts. Bull. Chem. Soc. Jpn. 1980, 53, 1366–1371.
23. Song, D.L.; Chen, Y.L.; Wang, R.X.; Liu, C.S.; Jiang, H.; Luo, G. Crossed-
aldol condensation of cycloalkanones with aromatic aldehydes catalyzed by
copper(II) trifluoroacetate. Prep. Biochem. Biotechnol. 2009, 39, 201–207.
24. Yanagihara, N.; Gotoh, T.; Ogura, T. Complex formations of silver(I) triflu-
oroacetate and trifluoromethanesulfonate with benzene and cyclohexene.
Polyhedron 1996, 15, 4349–4354.
7. Iranpoor, N.; Kazemi, F. RuCl3 catalyses aldol condensations of aldehydes
and ketones. Tetrahedron 1998, 54, 9475–9480.