An expeditious and solvent free synthesis of azine derivatives using sulfated anatase-titania as a novel solid acid catalyst

Article abstract of DOI:10.1016/j.catcom.2011.08.029

Solid acid catalyst sulfated anatase-titania (TiO₂-SO ₄^2-) has been used for the synthesis of azine derivatives from benzophenone hydrazone and ketones/aldehydes by simple physical grinding. This sulfated titania gives an

Full text of DOI:10.1016/j.catcom.2011.08.029

Catalysis Communications 16 (2011) 50–55
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Short Communication
An expeditious and solvent free synthesis of azine derivatives using sulfated anatase–
titania as a novel solid acid catalyst
⁎
B. Krishnakumar, M. Swaminathan
Department of Chemistry, Annamalai University, Annamalainagar 608 002, India
a r t i c l e i n f o
a b s t r a c t
Solid acid catalyst sulfated anatase–titania (TiO2–SO42−) has been used for the synthesis of azine derivatives from
benzophenone hydrazone and ketones/aldehydes by simple physical grinding. This sulfated titania gives an
excellent yield with short reaction time and is an inexpensive, easily recyclable catalyst for this reaction.
© 2011 Elsevier B.V. All rights reserved.
Article history:
Received 9 July 2011
Received in revised form 22 August 2011
Accepted 26 August 2011
Available online 14 September 2011
Keywords:
Sulfated titania
Azine
Lewis acidity
Green synthesis
1. Introduction
positively charged due to protonation as shown in Scheme 1, it becomes
more acidic. Surface acidity was determined by the spectrophotometric
Azines, R1R2C=N -N=CR1R2 have attracted great attention in organ-
ic synthesis as they are good synthons for obtaining heterocyclic com-
pounds such as pyrazoles, purines and pyrimidines [1–5]. These
compounds constitute an important class of compounds with unex-
pected biological activities [5–7]. The ability of azines derived from 2-
pyridinecarbaldehyde as polydentate ligand to form very stable com-
plexes with different cations is well known [8]. The usual method for
the preparation of azines involves treatment of carbonyl compounds
with hydrazine hydrate and acetic acid in ethanol [9,10]. A number of
methods have been reported for the synthesis of azines under various
conditions [11–15], but most of them require elevated temperatures
and complex catalysts. Hence, there is a need to develop a simple,
eco-friendly method under mild conditions for the preparation of
azines. Now the research in organic synthesis is mainly focused on the
use of environmental benign catalysts under solvent free condi-
tions [16–18]. Recently, Safari and Ravandi reported the synthesis of
azine derivatives with hydrazine sulfate and triethylamine under sol-
vent free conditions [19].
method based on the irreversible adsorption of an organic base pyridine
[21,22]. The amounts of pyridine adsorbed by 1 g of TiO2 and TiO2–SO42–
were 1600 and 2200 μg, respectively. This reveals that TiO2–SO42– has
more acidic sites when compared to bare TiO2.
Since synthesis of azine derivatives are rare in literature, herein
we report a recyclable, easily separable, eco-friendly and highly effec-
tive catalytic system TiO2–SO42− for the synthesis of azine derivatives
in excellent yield by simple physical grinding of reactants using a
mortar and pestle at room temperature. To the best of our knowledge
this is the first report of azine derivatives in this catalytic way.
2. Experimental
2.1. Materials and methods
Acetophenone, 4-methylacetophenone, 4-bromoacetophenone, 4-
chloroacetophenone, 4-fluoroacetophenone, benzophenone (s.d.fine),
benzaldehyde, 4-methylbenzaldehyde, 4-methoxybenzaldehyde, 4-
bromobenzaldehyde, 4-flurobenzaldehyde, 4-chlorobenzaldehyde, 4-
nitrobenzaldehyde, furfuraldehyde and pyridine-2-aldehyde (Aldrich
Chemicals) were used as received. AnalaR grade titanium isopropoxide
(Himedia 98.0%), 2-propanol (Spectrochem 99.5%), hydrazine hydrate
(s.d.fine) and H2SO4 (Fischer 98%) were used as such. Benzophenone-
hydrazone was prepared according to the literature procedure [23].
Preparation of TiO2–SO42– by sol–gel method and its characteriza-
tion by FT-IR, SEM, EDS, XRD and BET surface area measurements
were reported earlier [24,25]. Analysis of the SEM images of this cat-
alyst reveals that the particles are uniformly distributed in spherical
From a catalytic point of view, TiO2 possesses a unique type of surface
involving both redox and acid–base sites. In addition to high thermal sta-
bility, its amphoteric character makes titania, a promising catalytic mate-
rial. The textural and acid–base properties of titania depend greatly on
method of preparation. Loading of sulfate using H2SO4 makes the catalyst
more acidic [20] when compared to bare TiO2. Since the surface of TiO2 is
⁎
Corresponding author. Tel./fax: +91 4144 220572.
E-mail address: chemres50@gmail.com (M. Swaminathan).
1566-7367/$ – see front matter © 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.catcom.2011.08.029

B. Krishnakumar, M. Swaminathan / Catalysis Communications 16 (2011) 50–55
51
for 1 min. Completion of the reaction was tested by Thin Layer Chro-
matography (TLC). After completion of the reaction, ethanol was
added to the solidified mixture and the insoluble catalyst was separat-
ed by filtration. The filtrate was dried over anhydrous Na2SO4. The sol-
vent was evaporated to get the product. Then it was subjected to GC
and GC–MS analysis for the determination of the product yield. The
structure of product obtained was confirmed by FT-IR, 1H NMR, 13C
NMR and GC–MS analysis.
Scheme 1. Protonation of sulfated titania.
shape. It is found from XRD analysis that the catalyst is in nanoparti-
culate form, and the sulfate modification does not change its anatase
phase. The crystallite sizes of both prepared TiO2 and TiO2–SO42− are
34.7 and 11.6 nm, respectively. SO42− ion modification retarded the
aggregation. BET surface area of TiO2–SO42− (142 (m2 g−1)) is higher
than the prepared TiO2 (86 m2 g−1). Size reduction increases its sur-
face area, which enhances its catalytic activity in this reaction.
2.4. Preparation of bis(diphenylmethylidene)hydrazine, 3o — procedure
To a mixture of benzophenone hydrazone (1 mmol) and benzo-
phenone (1 mmol) in dry media, 0.1 g of TiO2–SO42− was added and
the mixture was irradiated under microwave oven at 480 W for
8 min. Completion of the reaction was tested by TLC. After completion
of the reaction, ethanol was added to the solidified mixture and the
insoluble catalyst was separated by filtration. The filtrate was dried
over anhydrous Na2SO4. The solvent was evaporated and the pure
product was obtained. Then it was subjected to GC and GC–MS anal-
ysis for the determination of the yield of the products. The structure
of product was confirmed by FT-IR, 1H NMR, 13C NMR and GC-MS
analysis. Spectral data of the some selected compounds are given
below.
2.2. Apparatus
IR spectra were recorded using an Avatar-330 FT-IR spectropho-
tometer using KBr pellets. For GC analysis, a Perkin-Elmer GC-9000
with a capillary column of DB-5 and flame ionization detector was
used. GC/MS analysis was carried out using a GC model: Varian GC–
MS-Saturn 2200 Thermo, capillary column VF5MS (5% phenyl–95%
methylpolysiloxane), 30 m length, 0.25 mm internal diameter,
0.25 μm film thickness, temperature of column range from 50 to
280 °C (10 °C min−1), and injector temperature 250 °C. Proton and
carbon NMR spectra were recorded on a BRUKER AVIII FT-NMR spec-
trometer operating at 400 MHz for all the samples.
2.5. 1-(Diphenylmethylidene)-2-(1-phenylethylidene)hydrazine, 3a
m.p.=105−107°C; IR (KBr) (cm−1)=3053, 3024, 2926, 2838,
1595, 1563, 1441, 1361, 1295, 782, 694; 1H NMR (CDCl3, 400 MHz) (δ,
ppm)=methyl proton 2.31 (s, 3H), other aromatic protons 7.11−7.62
(m, 15H), 13C NMR (CDCl3, 100 MHz) (δ, ppm)=methyl carbon 15.6
and other aromatic carbons 126.7, 127.8, 128.2, 128.3, 128.3, 128.8,
128.9, 129.5, 129.6, 129.8, 135.5, 138.3, 138.4 and two C_N 158.8 and
159.6; GC–MS (m/z)=299.2 (M+1).
2.3. Preparation of 1-(diphenylmethylidene)-2-(1-phenylethylidene)
hydrazine, 3a — procedure
To a mixture of benzophenone hydrazone (1 mmol) and acetophe-
none (1 mmol) in dry media, 0.1 g of TiO2–SO42− was added and the
mixture was ground in a mortar with a pestle at room temperature
Scheme 2. The condensation reaction of benzophenone hydrazone 1a with acetophenone 2a, benzaldehyde 2f and benzophenone 2o catalyzed by sulfated titania.

52
B. Krishnakumar, M. Swaminathan / Catalysis Communications 16 (2011) 50–55
Table 1
Synthesis of azine derivatives using sulfated titania under solvent free conditions.
Entry
1
Hydrazone
Ketones/aldehydes
Azines
Grinding time (s)
60
Yielda (%)
98.0
2
60
96.0
60
95.0
3
4
60
95.0
60
94.0
5
6
45
98.0
7
45
97.0

B. Krishnakumar, M. Swaminathan / Catalysis Communications 16 (2011) 50–55
53
Table 1 (continued)
Entry
Hydrazone
Ketones/aldehydes
Azines
Grinding time (s)
45
Yielda (%)
97.0
8
9
45
97.0
45
97.0
10
45
97.0
11
12
45
95.0
45
97.0
13
45
97.0
14
MW/8 min
98.0
15
a
Yield with respect to hydrazone (mol%).

54
B. Krishnakumar, M. Swaminathan / Catalysis Communications 16 (2011) 50–55
2.8. Bis(diphenylmethylidene)hydrazine, 3o
m.p. =163−165°C; IR (KBr) (cm− 1)=3079, 3054, 1638, 1564,
1487, 1442, 1318, 767, 659; 1H NMR (CDCl3, 300 MHz) (δ, ppm)=
aromatic protons 7.28−7.53 (m, 20H); 13C NMR (CDCl3, 300 MHz)
(δ, ppm)=aromatic carbons 127.8, 128.0, 128.6, 128.7, 129.3,
129.6, 135.5, 138.2 and C_N 158.9; GC–MS (m/z)=361.2 (M+1).
3. Results and discussion
When a mixture of benzophenone hydrazone (1 mmol) and aceto-
phenone (1 mmol) without catalyst was ground for 3 min no reaction oc-
curred. However, grinding the mixture with 0.1 g of TiO2–SO42− initiated
a condensation reaction producing 98 mol% 1-(diphenylmethylidene)-
2-(1-phenylethylidene)hydrazine (3a) in 60 s (Scheme 2), (Table 1,
entry 1). When bare TiO2 and ZrO2 were used in the same reaction
only trace of product was obtained. Sulfated ZrO2 was prepared from
ZrO2 by the procedure reported for sulfated TiO2-P25 [26] and used
for this reaction under the same conditions. Product yield was only
10 mol% with sulfated ZrO2.This reveals that TiO2–SO42− is more effi-
cient than sulfated ZrO2.
Fig. 1. Effect of catalyst loading. Catalyst=sulfated titania, benzophenone hydrazo-
ne=1 mmol, acetophenone=1 mmol, time=60 s (grinding at solvent free condition
in room temperature).
2.6. 1-benzylidene-2-(diphenylmethylidene)hydrazine, 3f
The effect of catalyst (TiO2–SO42−) dosage on the formation of
azine 3a was investigated by varying the catalyst amount from 0.05
to 0.2 g (Fig. 1). When the concentration of the catalyst is increased
from 0.05 to 0.1 g, formation of azine increases from 95.0 to
98.0 mol%. This is due to increase in the number of catalyst particles.
Above 0.1 g of the catalyst, no significant change in the percentage of
product formation occurred. The optimum catalyst loading is found to
be 0.1 g for the conversion of 1 mmol of benzophenone hydrazone.
In order to show the generality and scope of this new protocol, we
used various substituted ketones and aldehydes for condensation
with benzophenone hydrazone and the results obtained are summa-
rized in Table 1. Condensation with all aldehydes and ketones (except
benzophenone; Table 1, entry 15) proceeded very cleanly at room
temperature and no undesirable side-reactions were observed. Yields
were not much affected by the substituents present in the ketones
and aldehyes (Table 1, entries 1–12). Furfuraldehye and pyridine-2-
aldehyde also gave good yield (Table 1, entries 13 and 14). Overall, al-
dehydes react faster than ketones with benzophenone hydrazone.
m.p.=97−98°C; IR (KBr) (cm−1) =3055, 3025,1610, 1569, 1444,
1317, 765, 692; 1H NMR (CDCl3, 400 MHz) (δ, ppm)=N_C\H proton
8.62 (s, 1H), other aromatic protons 7.22−7.82 (m, 15H), 13C NMR
(CDCl3, 100 MHz) (δ, ppm)=C\H carbon 96.18 and other aromatic
and ipso carbons 128.1–159.2 and C_N 161.8, GC-MS (m/z)=285.1
(M+1).
2.7. 1-(4-bromobenzylidene)-2-(diphenylmethylidene)hydrazine, 3k
m.p.=103−105°C; IR (KBr) (cm−1) =3053, 2978, 2919, 1602,
1560, 1483, 1442, 1320, 1297, 776, 524; 1H NMR (CDCl3, 400 MHz)
(δ, ppm)=N_C\H proton 8.45 (s, 1H), other aromatic protons
7.27−7.69 (m, 15H), 13C NMR (CDCl3, 100 MHz) (δ, ppm)=C\H
carbon 96.18 and other aromatic and ipso carbons 125.1, 127.5,
128.1, 128.9, 129.2, 129.7, 130.2, 131.8, 133.5, 135.5, 138.1, 157.8
and C_N 166.2, GC–MS (m/z)=364.1 (M+1).
Scheme 3. Proposed mechanism for the condensation reaction of benzophenone hydrazone with acetophenone catalyzed by sulfated titania.

B. Krishnakumar, M. Swaminathan / Catalysis Communications 16 (2011) 50–55
55
Table 2
time. Another attractive feature of this green process is the reusability
of solid acid catalyst, sulfated titania.
Reusability of catalyst on condensation of benzophenone hydrazone (1 mmol) and
acetophenone (1 mmol) under grinding at room temperature.
Run
1
2
3
4
5
Acknowledgements
Yielda (TiO2–SO42−
)
98.0
98.0
98.0
97.0
97.0
a
One of the authors M.S is thankful to CSIR, New Delhi for financial
support through research grant No. 21(0799)/10/EMR-II. GC-MS facil-
ity provided by University Grants Commission, New Delhi under Spe-
cial Assistance Program is gratefully acknowledged. One of the
authors B.K is thankful to CSIR, New Delhi, for the award of Senior Re-
search Fellowship.
Yields with respect to benzophenone hydrazone (mol%).
However, in the case of benzophenone, no reaction was observed
when it was ground with benzophenone hydrazone at room temper-
ature for 10 min in the presence of TiO2–SO42−. No product was
obtained even by refluxing the mixture in alcohol (Scheme 2). This
may be due to steric effect of two phenyl groups present in the ben-
zophenone. This steric effect is also reflected with benzaldehyde
and acetophenone. Benzaldehyde reacts faster than acetophenone
with benzophenone hydrazone. Hence, synthesis of benzophenone
azine was carried out under microwave irradiation. The use of micro-
waves in organic synthesis has attracted considerable attention in re-
cent years due to short reaction time and improved product yield
[27–29].
When a mixture of benzophenone hydrazone (1 mmol) and ben-
zophenone (1 mmol) without solvent was irradiated in microwave
oven (480 W) for 10 min, no reaction was observed. But addition of
a 0.1 g of TiO2–SO42− to this mixture initiated condensation reaction
producing 98 mol% 1,2-bis(diphenylmethylene)hydrazine in 8 min
under microwave irradiation (Scheme 2) (Table 1, entry 15).
Since the sulfated titania has more acidic sites, acid catalyzed
mechanism is proposed for this reaction (Scheme 3). This mechanism
involves the protonation of hydrazone with acidic TiO2–SO42−. This
protonated hydrazone 1 condenses with acetophenone forming an
intermediate 2 which on dehydration and deprotonation produces
the product azine 3. Solid acid catalyst TiO2–SO42− promotes dehydra-
tion and deprotonation. The possibility of recycling the catalyst was
examined for the reaction of benzophenone hydrazone with aceto-
phenone. When the reaction was complete, ethanol was added to
the solidified mixture and the insoluble catalyst was separated by fil-
tration. The separated catalyst could be used five times without any
treatment and, no appreciable loss in its catalytic activity was ob-
served up to fifth run (97.0 mol%) (Table 2, entry 5).
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4. Conclusions
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