Mesoporous titanosilicate Ti-TUD-1 catalyzed Knoevenagel reaction: An efficient green synthesis of trisubstituted electrophilic olefins

Article abstract of DOI:10.1016/j.catcom.2010.01.003

A new, efficient and green methodology has been developed for the Knoevenagel condensation using catalytic amount of mesoporous titanosilicate catalyst Ti-TUD-1, under mild conditions at room temperature. The method generates trisubstituted electrophilic olefins in high yields within short reaction time. The mesoporous nature of the catalyst having high surface area helps in binding the substrate to the active site. The advantage of this catalyst is its reusability with almost consistent reactivity thereby making it viable for industrial applications.

Full text of DOI:10.1016/j.catcom.2010.01.003

Catalysis Communications 11 (2010) 601–605
Contents lists available at ScienceDirect
Catalysis Communications
journal homepage: www.elsevier.com/locate/catcom
Mesoporous titanosilicate Ti-TUD-1 catalyzed Knoevenagel reaction:
An efficient green synthesis of trisubstituted electrophilic olefins
a,
Bikash Karmakar a, Biswajit Chowdhury b, , Julie Banerji
*
*
a Centre of Advances Studies on Natural Products including Organic Synthesis, Department of Chemistry, University of Calcutta, 92, A.P.C. Road, Kolkata 700 009, India
b Department of Applied Chemistry, Indian School of Mines University, Dhanbad 826 004, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 10 August 2009
Received in revised form 16 December 2009
Accepted 7 January 2010
Available online 11 January 2010
A new, efficient and green methodology has been developed for the Knoevenagel condensation using cat-
alytic amount of mesoporous titanosilicate catalyst Ti-TUD-1, under mild conditions at room tempera-
ture. The method generates trisubstituted electrophilic olefins in high yields within short reaction
time. The mesoporous nature of the catalyst having high surface area helps in binding the substrate to
the active site. The advantage of this catalyst is its reusability with almost consistent reactivity thereby
making it viable for industrial applications.
Keywords:
C–C coupling
Ó 2010 Elsevier B.V. All rights reserved.
Active methylene compounds
Aldehydes
Mesoporous catalyst
Recyclable
1. Introduction
environment friendly catalytic methodology. Supported porous so-
lid acids would be an effective solution of the problem. In contin-
In recent times attention has been focused on the development
of eco-friendly solid acid/base catalysts for organic synthesis. The
advantage of these catalysts lies in their high atom efficiency, ex-
treme selectivity and simple work-up procedure without generat-
ing any organic waste. Development of catalysts for C–C bond
formation in organic synthesis following green approach always
provides a challenge. One such example is the versatile Knoevena-
gel condensation reaction [1,2], a useful method for the synthesis
of active dipolarophiles which finds application in 1,3-cycloaddi-
tion reactions [3]. The reaction also has wide application in the
synthesis of drugs [4], polymer sciences [5], and natural products
[6].
uation to our exploration of green synthetic methodology using
porous solids [10,11], we would like to report here the efficiency
of the mesoporous titanosilicate catalyst Ti-TUD-1 [12,13] towards
the classical Knoevenagel condensation reaction. The catalyst has
high surface area and Ti, being in a highly dispersed state on the
silica surface, is catalytically highly active. We are the first to re-
port the use of this catalyst in the Knoevenagel condensation reac-
tions at room temperature with high selectivity and quantitative
yields (Scheme 1).
2. Experimental
The classical Knoevenagel condensation involves the condensa-
tion of aldehydes/ketones with active methylene compounds in the
presence of organic bases like pyridine, piperidine and ethylenedi-
amine [7–9]. Normally malononitrile, cyanoesters, b-ketoesters,
malonic acids, malonates are used as the active methylene compo-
nents containing two electron withdrawing groups (EWG). How-
ever, the procedure results in a large amount of organic wastes
due to polymerization and self condensation reactions. Hence,
comes the necessity and importance of developing a clean and
2.1. General
The NMR spectra (1H and 13C NMR) were recorded on a Bruker
Avance 300 MHz and Bruker Avance 75.5 MHz spectrometer and
TMS was used as the internal standard. Infrared spectra were re-
corded in KBr pellet in reflection mode with a Perkin–Elmer RX-1
FT-IR spectrophotometer. X-ray powder diffraction study was car-
ried out on a Philips PW-1830 X-ray diffractometer at a voltage of
35 kV and a current of 25 mA using Cu Ka radiation (k = 154 nm) at
the scanning rate of 1°/min in the 2h range 0–5° and 10–70°. SEM
was performed with a Hitachi-S 3400N microscope at an operating
voltage of 15 kV. The sample was coated with gold for effective
imaging before being charged. TEM images were obtained from a
JEOL JEM-2100 Transmission Electron Microscope at an operating
* Corresponding authors. Tel.: +91 326 223 5663; fax: +91 326 222 4072 (B.
Chowdhury), tel.: +91 33 2350 8386; fax: +91 33 2351 9755 (J. Banerji).
E-mail addresses: biswajit_chem2003@yahoo.com (B. Chowdhury), juliebaner
ji47@gmail.com (J. Banerji).
1566-7367/$ - see front matter Ó 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.catcom.2010.01.003

602
B. Karmakar et al. / Catalysis Communications 11 (2010) 601–605
solution. A mixture of triethanolamine (TEA) and water was
R1
R2
R1
R2
R3
O
added to a stirring solution and then triethyl ammonium hydrox-
ide (TEAOH) (20% aqueous solution) was added dropwise to pH
10. The final molar ratio of the reagents was 1.0 SiO2:m TiO2
(m = 0.01, 0.03, 0.05):3.0 TEA:0.3 TEAOH:15 H2O. The clear solu-
tion was aged for 24 h at room temperature. It was then dried
at 115 °C for 16 h and finally calcined at 700 °C for 12 h at the
rate of 2 °C/min under the flow of air. The nature of the as syn-
thesized calcined product was glassy crystalline.
Ti-TUD-1
Ethanol, rt
+
R3
H
H
R1,R2 = CN; R3 = Aryl, Cinnamyl, Furoyl
Scheme 1. Knoevenagel condensation reaction.
voltage of 100 kV. The sample was prepared by placing one drop of
the dispersed solution of the catalyst in acetone as solvent on a car-
bon coated copper grid followed by drying over air. The emission
fluorescence spectrum was recorded on a Perkin–Elmer spectro-
photometer. Melting points (uncorrected) were determined on a
Koffler Block apparatus. Synthetic grade chemicals from Acros
and E-Merck were used for the preparation of the catalyst and from
Spectrochem for carrying out the organic reactions. Analytical TLC
was performed using E-Merck aluminium-backed silica gel plates
coated with silica gel G. For column chromatography 60–120 mesh
silica gel was used from Merck. All the solvents used in the reaction
were distilled and dried over Na2SO4.
2.3. Typical reaction procedure
The aldehyde (0.2 g, 1.0 equiv.) and active methylene com-
pound (0.14 g, 1.1 equiv.) were taken in a 50 mL round bottom
flask. Five millilitres solvent was added and stirred at room tem-
perature. Then the catalyst (0.02 g) was added and stirring was
continued under normal atmosphere till the starting materials
were no longer present (by TLC technique). The reaction mixture
was separated from the catalyst by centrifugation. After drying un-
der vacuum, the crude product was purified by column chromatog-
raphy using 60–120 mesh silica gel and appropriate mixture of
ethyl acetate/hexane as eluent. The purified products were charac-
terized by IR spectroscopy, 1H NMR and 13C NMR spectrometry and
elemental analysis.
2.2. Catalyst preparation
The mesoporous titanosilicate Ti-TUD-1 was prepared follow-
ing a simple and modified synthetic procedure. Modifications
were done in terms of tuning of porosity development mecha-
nism where a non-hydrothermal sol–gel technique was used
and higher content of structure directing template. Tetraethyl
orthosilicate (TEOS) and titanium (IV) butoxide were used as
the precursor for silica and titanium, respectively. In the typical
procedure titanium butoxide was added slowly to the TEOS
3. Results and discussion
3.1. Characterization of the catalysts
Mesoporous Ti-TUD-1 (Ti/Si mole ratio = 0.01, 0.03, 0.05, re-
ferred to as catalysts Ti-1-TUD-1, Ti-3-TUD-1, Ti-5-TUD-1, respec-
tively) catalysts were prepared by non-hydrothermal sol–gel
Fig. 1. SEM images of the surface morphology (A and B); TEM images of the lamellar channels (C) and porous surface (D) of the catalyst Ti-3-TUD-1.

B. Karmakar et al. / Catalysis Communications 11 (2010) 601–605
603
method and modified from that followed by Maschmeyer et al.
[12]. They were characterized by Scanning Electron Micrograph
(SEM), Transmission Electron Microscopy (TEM), Powder X-ray dif-
fraction (XRD), Fluorescence emission spectroscopy and surface
area analysis by BET (Brunnauer–Emett–Teller) method. SEM
images (Fig. 1A and B) depict the surface morphology of the mate-
rial. Apparently the surface is spongy in nature. The particles are of
uneven shape and size. TEM images (Fig. 1C and D) of the catalyst
surface reflect a highly porous and wormhole-like arrangement.
There are mixtures of small and large pores well distributed over
the entire surface. Pore sizes found to range between 5 and
15 nm. The porous channels formed are also visible in the image.
The pores are in the parallel arrangement with channels. However,
the identification of Ti atoms could not be detected from TEM
images. XRD spectral analysis was done with the catalyst Ti-3-
TUD-1. Both the low angle and wide angle diffraction patterns
were studied (Fig. 2). A sharp peak was observed in the 2h range
0.5–1.0° which is a clear indication of the sample being mesopor-
ous in nature [12]. A broad diffraction band at around 2h = 25° con-
firmed the amorphous silica matrix [14]. However, the XRD spectra
did not show the characteristic diffraction lines for anatase or ru-
tile titania phase [15] which indicates that there was no free tita-
nium dioxide formed in the catalyst matrix. From the
fluorescence emission spectra of Ti-5-TUD-1 catalyst (Fig. 3), the
well defined characteristic bands of Ti were discernible. A sharp
maxima at 425 nm appeared due to Ti4+ emission [16]. Due to high
porosity, the surface area was also found to be high. BET surface
area of the catalysts was found to range between 380 and
450 m2/g. However, since the catalysts were prepared by a non-
hydrothermal method, the development of pores might be less
effective than hydrothermal method. Again due to loading the sur-
face area was found to be somewhat lower than that prepared
hydrothermally.
amorphous TiO2 did not generate satisfactory yields. The Ti-3-TUD-
1 catalysts with Ti/Si molar ratio 0.03 furnished the best yield. The
optimization of the conditions was carried out using the best cat-
alyst with different solvent variation. The observations have been
B
1000
800
600
400
200
250
300
350
400
450
500
550
Wavelength (nm)
Fig. 3. Fluorescence emission spectrum of Ti-5-TUD-1 catalyst.
Table 1
Survey on the variation of catalysts.a
Entry
Catalyst
Time (h)
Yieldb (%)
1
2
3
4
6
7
None
TUD-1
TiO2
Ti-1-TUD-1
Ti-3-TUD-1
Ti-5-TUD-1
24
24
12
0.5
0.5
0.5
Trace
27
52
86
91
78
3.2. Study of catalytic activity
a
Reaction conditions: benzaldehyde (1 mmol), malononitrile (1.1 mmol), catalyst
(10 wt.%), ethanol (5 mL), rt.
Knoevenagel condensation reactions were studied using
aromatic aldehydes and active methylene compounds over Ti-
TUD-1. In order to show the efficacy of this catalyst, comparative
studies were made with several catalysts along with the Ti-TUD-
1 with different Ti loadings. The results have been summarized
in Table 1. Primarily benzaldehyde was treated with malononitrile
in ethanol at room temperature. Mesoporous silica TUD-1 and bulk
b
Isolated yield after purification.
Table 2
Solvent screening for the Knoevenagel condensation.a
Entry
Solvent
Time (h)
Yieldb (%)
1
2
3
4
5
6
Toluene
DCM
Acetonitrile
Ethanol
THF
24
12
2
0.5
6
31
47
73
91
55
64
DMF
6
a
Reaction conditions: benzaldehyde (1 mmol), malononitrile (1.1 mmol), Ti-TUD-
1 catalyst (10 wt.%), ethanol (5 mL), rt.
b
Isolated yield after purification.
1
2
3
4
5
2θ
Table 3
Variation of the active methylene components.a
Entry
Active methylene group
Time (h)
Yieldb (%)
1
2
3
4
5
6
Malononitrile
Ethyl cyanoacetate
Acetylacetone
Ethyl acetoacetate
Diethyl malonate
Acetoacetanilide
0.5
1.2
6
6
6
91
82
38
54
Trace
Trace
10
20
30
40
50
60
70
6
2θ
a
Reaction conditions: benzaldehyde (1 mmol), active methylene component
(1.1 mmol), Ti-TUD-1 catalyst (10 wt.%), ethanol (5 mL), rt.
Fig. 2. Wide angle and low angle (inset) powder X-ray diffraction pattern of Ti-3-
TUD-1 catalyst.
b
Isolated yield after purification.

604
B. Karmakar et al. / Catalysis Communications 11 (2010) 601–605
shown in Table 2. Ethanol yielded the best result in terms of time
and yield. This was probably due to stabilization of the enolate of
the active methylene compound and the polarized complex of
aldehyde in ethanol due to solvation.
(entries 8–12). Unsaturated aldehyde like trans-cinnamaldehyde
(entry 13) or acid sensitive heterocycle like furfural (entry 14) fur-
nished products in significantly good yield. In all the cases, the
reaction product showed exclusive E selectivity as confirmed from
NMR spectroscopy.
The high catalytic activity of Ti-TUD-1 is possibly due to the
easy accessibility of the substrate molecules to the catalytic sites
of the mesoporous system where Ti4+ is in tetrahedral coordination
and symmetrically dispersed over the 3D surface. Ti-TUD-1 per-
forms a dual role, polarizing the aldehydes to increase carbonyl
activity and also binds with the active methylene carbon to form
a stable enolate complex. The latter then attacks the polarized car-
bonyl group and subsequently water elimination takes place to
furnish the product. The plausible reaction pathway is summarized
in Scheme 2.
The reactivity of various active methylene compounds with
benzaldehyde was also studied using catalyst Ti-3-TUD-1 in etha-
nol and the results are shown in Table 3. Malononitrile was found
to be the most effective among the all active methylene com-
pounds due to better electron withdrawing effect which was evi-
dent from the reaction time and yield. Reactions with several
other active methylene compounds were attempted but the prod-
ucts were not obtained in good yields. Possibly, the lower activa-
tion of the methylene group and hence the formation of less
stable enolate with Ti appeared to be the cause.
On standardizing the condition a series of reactions were car-
ried out using various aromatic aldehydes and malononitrile and
the results have been recorded in Table 4. The reactions went
smoothly with aromatic aldehydes containing different functional-
ities producing remarkably good yields (entries 1–8). Strong elec-
tron withdrawing effect of nitro groups (entries 2–3) or the
strong electron donating effect due to NMe2 group (entry 7)
showed the effect on yield and reaction time. The method was also
found suitable for methoxyl substituted aromatic aldehydes
3.2.1. Representative characterization data
3.2.1.1. 2-[(3,4-Dimethoxyphenyl) methylidene] propanedinitrile
3k. Bright yellow crystalline solid, mp 142 °C; IR (KBr): 3437.2,
2222.9, 1573.1, 1501.5, 1333.9, 1129.9 cmÀ1 1H NMR (300 MHz,
;
CDCl3) d 8.30 (s, 1H), 7.54–7.60 (m, 2H), 7.17 (s, 1H), 3.83 (s, 3H),
3.77 (s, 3H); 13C NMR (75.5 MHz, CDCl3) d 160.75, 154.58, 148.89,
127.38, 124.25, 114.9, 114.15, 112.12, 112.08, 76.8, 56.17, 55.6;
Table 4
Knoevenagel condensation between different aldehydes and malononitrile as active methylene compound.a
CN
CN
R
H
CN
CN
1
O
Ti-TUD-1
Ethanol, rt
+
R
H
2
3
Entry
R
Product 3b
Time (min)
Yield (%)c
1
2
3
4
5
6
7
8
C6H5
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
30
20
20
60
40
90
120
90
120
75
90
45
75
30
91
95
88
82
84
81
77
86
84
81
80
84
79
94
4-NO2–C6H4
3-NO2–C6H4
4-CH3–C6H4
4-Cl–C6H4
4-OH–C6H4
4-NMe2–C6H4
4-OCH3–C6H4
3-OCH3–C6H4
Vanillyl
9
10
11
12
13
14
3,4-di OMe–C6H3
3,4,5-tri OMe–C6H2
C6H4 CH@CH
Furfuryl
a
b
c
Reaction conditions: aldehyde (1 mmol), malononitrile (1.1 mmol), Ti-TUD-1 catalyst 10 wt.%, ethanol (5 mL), rt.
Only E isomer was formed as confirmed from NMR spectroscopy.
Isolated yield after purification.
Si
O
Ti
Ar
NC
NC
NC
Ar
Ethanol
Ti
H2O
H
N
N
NC
OH
H
Ar
Si
O
O
H
polarized complex
of aldehyde
enolate complex
of malononitrile
Scheme 2. Probable mechanism of the Knoevenagel condensation.

B. Karmakar et al. / Catalysis Communications 11 (2010) 601–605
605
Table 5
4. Conclusion
Recycling of the catalyst.a
Cycles
Benzaldehyde (g)
Catalyst (mg)
Yield (%)b
We have developed a new inexpensive, reusable and environ-
mentally benign catalytic process using mesoporous solid acid cat-
alyst Ti-TUD-1 for the C@C bond formation in Knoevenagel
condensation reaction under mild conditions with high selectivity
and excellent yield. No side reactions like self condensation, dimer-
ization and rearrangements were observed. The catalyst can be
easily recovered from the reaction mixture by centrifugation and
there no trace of leaching of Ti could be detected in the filtrate.
Ti-TUD-1 therefore provides an efficient and excellent alternative
to the classical catalysts used in the versatile Knoevenagel conden-
sation reaction.
Fresh
0.5
0.4
0.35
0.2
0.1
50
40
35
20
10
91
88
88
85
82
1
2
3
4
a
Reaction conditions: benzaldehyde (1 mmol), malononitrile (1.1 mmol), Ti-TUD-1
catalyst 10 wt.%, Ethanol (5 mL), rt.
b
Isolated yield after purification.
Anal. Calcd. for C12H10N2O2: C, 67.28; H, 4.71; N, 14.94. Found: C,
67.31; H, 4.75; N, 14.88.
Acknowledgements
J.B. would like to thank UGC, New Delhi, India for financial
assistance. B.C. thanks DST Fast Track Young Scientist Sceme,
New Delhi, India. B.K. thanks Dr. P.K. Maiti, Mr. P. Dasgupta, Mr.
P. Ghosh for instrumental analysis and Miss. S. Ghosh for technical
help.
3.2.1.2. 2-[(3,4,5-Trimethoxyphenyl) methylidene] propanedinitrile
3l. Pale yellow crystalline solid, mp 140 °C; IR (KBr): 3436.0,
2216.6, 1570.6, 1507.0, 1269.5, 1141.9 cmÀ1 1H NMR (300 MHz,
;
CDCl3) d 8.34 (s, 1H), 7.33 (s, 2H), 3.78 (s, 3H), 3.77 (s, 6H); 13C
NMR (75.5 MHz, CDCl3) d 161.46, 152.96, 126.45, 114.46, 113.71,
108.64, 79.6, 60.94, 56.17, 48.66; Anal. Calcd. for C13H12N2O3: C,
63.93; H, 4.95; N, 11.47. Found: C, 63.96; H, 4.91; N, 11.49.
References
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catalyst was performed through condensation of benzaldehyde
and malononitrile. Under the stabilized condition the reaction
was carried out in presence of Ti-3-TUD-1 catalyst. After comple-
tion of the reaction, the reaction mixture was centrifuged at
3000 rpm for 10 min and the supernatant layer was decanted.
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well at 60 °C for 4 h and was reused five consecutive times with the
fresh batch of reactants following same process. All the batches
proceeded smoothly with almost reproducible results each time
(Table 5) which proved the reusability of the catalyst. Atomic
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