TiO2 and TiO2 nanoparticles as efficient and recoverable catalysts for the synthesis of pyran annulated heterocyclic systems

Article abstract of DOI:10.1007/s11164-012-0766-8

TiO₂ catalyzed reactions between various activated CH-acids and tetracyanoethylene are described. This reaction affords the corresponding pyran annulated heterocyclic systems in high yields at room temperature in 3 h. The work-up procedure is v

Full text of DOI:10.1007/s11164-012-0766-8

Res Chem Intermed (2013) 39:2401–2406
DOI 10.1007/s11164-012-0766-8
TiO2 and TiO2 nanoparticles as efficient
and recoverable catalysts for the synthesis
of pyran annulated heterocyclic systems
•
Nasser Babakhani Sajjad Keshipoor
Received: 17 May 2012 / Accepted: 7 August 2012 / Published online: 18 August 2012
Ó Springer Science+Business Media B.V. 2012
Abstract TiO2 catalyzed reactions between various activated CH-acids and tetracy-
anoethylene are described. This reaction affords the corresponding pyran annulated
heterocyclic systems in high yields at room temperature in 3 h. The work-up procedure
is very simple, and the products do not require further purification. The catalysts can be
recycled and reused several times without observable loss of performance.
Keywords TiO2 Á Pyran Á Green chemistry Á Nano-particles Á Tetracyanoethylene
Introduction
With increasing concern about environmental pollution troubles and the importance
of healthy and productive life in harmony with nature, there has been remarkable
interest in developing new routes that reduce pollution in chemical synthesis. Water
as a solvent and heterogeneous catalysis are keys to successful development of so-
called ‘‘green chemistry’’. Therefore, these two factors are widely studied for
optimizing reaction conditions [1]. The use of organic solvents required to conduct
chemical reactions creates ecological and economic concerns. The hazardous nature
of these solvents and the consequence of them in the environment, and their urgent
deletion or replacement with H2O, have been a major emphasis of green chemistry
[2–4]. In the last decade, a large number of publications have demonstrated the
value of H2O or aqueous media for chemical reactions [5, 6]. The ease of handling,
simple work-up, and regenerability of heterogeneous catalysts induced makes them
of great interest in industrial catalytic processes. TiO2 as a heterogeneous catalyst
whas been applied for diverse industrial applications, e.g. in the selective reduction
of NOx in stationary sources, photocatalysis for pollutant elimination or organic
N. Babakhani Á S. Keshipoor (&)
Islamic Azad University, Miyandoab Branch, Miyandoab, Iran
e-mail: sa.keshipoor@yahoo.com
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N. Babakhani, S. Keshipoor
NC CN
CN
O
O
NC
NC
CN
CN
TiO2
H2O. r.t.,
O
O
NH2
2
1
3
Scheme 1 Reaction between TCNE and CH-acids in the presence of TiO2 as the catalyst
synthesis, photovoltaic devices, sensors, and paints [7–10]. Nanocrystalline metal
oxides have unusual magnetic, physical and surface chemical and catalytic properties
[11–15]. These materials can exist with numerous surface sites and enhanced surface
reactivity, such as crystal corners, edges or ion vacancies [16]. Nanocrystalline TiO2
has been applied as a catalyst for the Friedel–Craft’s alkylation of indoles with
epoxides [17].
Pyrans as naturally-occurring compounds [18, 19] have useful biological
activities, such as spasmolytic, diuretic, anti-coagulant, anti-cancer, and anti-
anaphylactic [20–23]. They are interesting due to their therapeutic applications such
as cognitive enhancers. They are also used for the treatment of neurodegenerative
diseases including Alzheimer, amyotrophic lateral sclerosis, Huntington, Parkinson,
AIDS-associated dementia and Down’s syndrome, as well as for the treatment of
schizophrenia and myoclonus [24]. Thus, new methods for the synthesis of pyran
derivatives and their optimization is of great interest [25–28].
Here, in a greener approach, the synthesis of pyran annulated heterocyclic
systems 3a–i was developed in the presence of TiO2 as the heterogeneous recyclable
catalysts, in H2O at room temperature (Scheme 1).
Results and discussion
In a pilot experiment, the reaction of 5,5-dimethylcyclohexane-1,3-dione (1d)
(1 mmol) with TCNE (2) (1 mmol) in the presence of TiO2 (0.02 g) in H2O (10 mL)
was investigated. This reaction afforded 2-amino-7,7-dimethyl-5-oxo-6,7,8,8a-tetra-
hydro-4H-chromene-3,4,4(4aH,5H)-tricarbonitrile (3d) in 75 % yield after 3 h
(Scheme 1).
Treatment of various CH-acids 1 such as cyclopentane-1,3-dione (1a), tetronic
acid (1b), cyclohexane-1,3-dione (1c), dimedone (1d), 1,3-dimethylpyrimidine-
2,4,6(1H,3H,5H)-trione (1e), 4-hydroxy-6-methyl-2H-pyran-2-one (1f), 4-hydroxy-
2H-chromen-2-one (1g) and 4-hydroxy-1-methylquinolin-2(1H)-one (1h) with
TCNE (2) in the presence of TiO2 in H2O at room temperature led to the formation
of the corresponding pyran’s annulated heterocyclic systems 3a–i in high yields
(Fig. 1).
Next, the reaction was examined in the presence of TiO2 nanoparticles (NPs) as
the catalyst under the same reaction conditions. TiO2 NPs showed partially good
performance rather than TiO2 and somewhat increased reaction yields. Therefore,
we decided to investigate TiO2 NPs as a catalyst in this reaction for all of the
compounds 1. The results are summarized in Fig. 1 .
123

TiO2 and TiO2 nanoparticles as efficient and recoverable catalysts
2403
O
N
O
O
NC CN
NC CN
NC CN
NC CN
O
NC CN
O
CN
CN
CN
CN
CN
N
O
O
O
NH2
O
NH2
O
NH2
O
NH2
O
NH2
3c
3e
3b
3d
3a
O
NC CN
O
O
O
NC CN
NC CN
NC CN
CN
CN
NH2
CN
CN
O
N
O
N
NH2
N
O
O
NH2
O
NH2
Ph
3i
3f
3g
3c
3h
3g
80
86
3d
3e
3f
3h
3i
3a
3b
Product
Yielda(%)
Yieldb(%)
75
80
73
77
74
83
75
81
79
80
80
83
71
80
70
72
192-194
Found 178-180 186-188 196-198 198-200 210
Reportedc
M. P.
(oC)
203 220
219
178-181 186-188 196-197 196-201 210-213 203
220-222 220-222
-
aIn the presence of TiO2
bIn the presence of TiO2 NPs
cRef [28]
Fig. 1 Structures, melting points [28] and yields of products 3a–i
Recyclability of the catalysts was also examined. For this reason, catalysts, which
were recovered from the reaction between 5,5-dimethylcyclohexane-1,3-dione (1d)
and TCNE 2 by filtration, washed with CH2Cl2 (2 9 5 ml) and dried in the oven
(70 °C, 6 h), were used again. This procedure was carried out four times. The
results of these successive reactions are shown in Table 1. It is clear that, during
successive use of the catalyst, no decrease in the reactivity or performance can be
seen for TiO2, but TiO2 NPs does not show good recoverability.
Although no detailed mechanistic studies have been carried out at this point, it is
conceivable that the initial event is the activation of TCNE (2) via coordination with
TiO2. Then, the cyclic CH-acid 1 undergoes nucleophilic addition to activated
TCNE to produce intermediate 4 which, via intramolecular cyclization, afforded
products 3a–i (Scheme 2).
Table 1 Recycle of catalysts
Cycle
TiO2 (g)
Yield (%)a
TiO2 NPs (g)
Yield (%)a
1
2
3
4
0.018
0.017
0.015
0.015
75
75
73
71
0.016
0.012
0.011
0.010
81
80
80
79
Reaction conditions: 5,5-dimethylcyclohexane-1,3-dione (1d) (1 mmol), TCNE (2) (1 mmol), H2O
(10 mL), room temperature, 3 h
a
Isolated yield
123

2404
N. Babakhani, S. Keshipoor
Scheme 2 The proposed
mechanism for the formation of
pyrans 3a–i in the presence of
TiO2
O
NH2
CN
NC CN 3a-i
TiO2
N
O
CN
TiO2
H
CN
Ph
NC
NC
CN
CN
4
O2Ti
N
1
CN
CN
NC
O
O
H
2
2
Here, we want to solve two problems. The first problem is when using the
homogeneous catalyst, such as separation and regeneration, and the second problem
is the application of organic solvent. Successively, we overcame these problems by
using a heterogeneous catalyst in H2O. The separation of TiO2 and TiO2 NPs from
the reaction medium was easily carried out by filtration. After drying, it was reused
for subsequent reactions (Table 1). Thus, this process could be interesting for large-
scale synthesis.
Conclusions
In conclusion, we have developed a rapid and efficient approach for the synthesis of
pyran annulated heterocyclic systems under mild reaction conditions in H2O in the
presence of TiO2 and TiO2 NPs with fairly good yields. The present method has the
advantages that not only can the catalysts be recycled and reused for several times
without loss of performance but also the substances can be mixed without any
modification. The work-up procedures are very simple, and the products do not
require further purification. The simplicity of the present procedures and the
environmental friendliness of this route makes it an interesting alternative to other
approaches.
Experimental
Melting points were measured on an Electrothermal 9100 apparatus and are
uncorrected. IR spectra were recorded in KBr on a Shimadzu IR-470 spectrometer.
123

TiO2 and TiO2 nanoparticles as efficient and recoverable catalysts
2405
1H NMR Spectra were recorded on a Bruker DRX-300 Avance spectrometer
300.13 MHz. The 13C NMR spectra were recorded at 75.47 MHz; for all NMR
spectra data, chemical shifts (d scale) are reported in parts per million (ppm). The
elemental analyses were performed with an Elementar Analysensysteme VarioEL.
The chemicals used in this work were purchased from Merck and Fluka Chemical.
TiO2 NPs were purchased from Aldrich with particle size \100 nm.
Typical procedure for preparation of 6-amino-3-methyl-1-phenylpyrano[2,3-
c]pyrazole-4,4,5(1H)-tricarbonitrile (3i)
To a magnetically stirred solution of tetracyanoethylene (0.13 g, 1.0 mmol) in H2O
(10 ml), TiO2 (0.02 g) and 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one (0.17 g, 1.0
mmol) was added at room temperature and the reaction mixture was stirred for 3 h.
After completion of the reaction, the solvent was removed under reduced pressure.
Then, CH2Cl2 was added to the residue and the solid catalyst was separated from the
reaction mixture by filtration. Then, crystallization from CH2Cl2/nhexane 1:2 afforded
3i as a white powder (0.21 g, yield 70 %); Mp 192–194 °C; IR: 3,421, 3,329, 2,210,
1,747, 1,656, 1,536, 1,413 cm-1; 1H NMR (300 MHz, CDCl3) d: 2.11 (s, 3H, CH3),
7.31–7.47 (m, 5H, Ar–H), 8.63 (br s, 2H, NH2). 13C NMR (75 MHz, CDCl3) d: 37.26,
56.7, 91.2, 111.4, 117.3, 121.6, 122.1, 126.7, 129.1, 140.1, 142.3, 148.3, 160.9; Anal.
calcd. for C16H10N6O: C 63.57, H 3.33, N 27.80; Found C16H10N6O: C 63.56, H 3.33,
N 27.83.
Acknowledgment We gratefully acknowledge financial support from the Research Council of the
Islamic Azad University of Miyandoab.
References
1. B.K. Min, C.M. Friend, Chem. Rev. 107, 2709 (2007)
2. G. Nagendrappa, Resonance 7, 59 (2002)
3. R.S. Varma, V.V. Namboodiri, Pure Appl. Chem. 73, 1309 (2001)
4. R.S. Varma, Green Chem. 1, 43 (1999)
5. P.A. Grieco, Organic Synthesis in Water (Blackie, New York, 1998)
6. D.J. Adams, P.J. Dyson, S.J. Tavener, Chemistry in Alternative Reaction Media (Wiley, New York,
2003)
7. H. Bosh, F. Janssen, Catal. Today 2, 369 (1988)
8. P. Forzatti, Catal. Today 62, 51 (2000)
9. M.R. Hoffman, S.T. Martin, W. Choi, D.W. Bahnemann, Chem. Rev. 95, 69 (1995)
10. A. Maldoti, A. Molinari, R. Amadeni, Chem. Rev. 102, 3811 (2002)
11. H. Itoh, S. Utamapanya, J.V. Stark, K.J. Klabunde, J.R. Schlup, Chem. Mater. 5, 71 (1993)
12. Y. Jiang, C. Decker, C. Mohs, K.J. Klabunde, J. Catal. 180, 24 (1998)
13. J. Guzman, B.C. Gates, Nano Lett. 1, 689 (2001)
14. B.M. Choudary, R.S. Mulukutla, K.J. Klabunde, J. Am. Chem. Soc. 125, 2020 (2003)
15. B.M. Choudary, M.L. Kantam, K.V.S. Ranganath, K. Mahender, B. Sreedhar, J. Am. Chem. Soc.
126, 3396 (2004)
16. R. Richards, W. Li, S. Decker, C. Davidson, O. Koper, V. Zaikovski, A. Volodin, T. Rieker, J. Am.
Chem. Soc. 122, 4921 (2000)
17. M.L. Kantam, S. Laha, J. Yadav, B. Sreedhar, Tetrahedron Lett. 47, 6213 (2006)
18. J.A. Ciller, N. Martin, C. Seoane, J.L. Soto, J. Chem. Soc. Perkin Trans. 1, 2581 (1985)
19. S. Hatakeyama, N. Ochi, H. Numata, S. Takano, J. Chem. Soc. Chem. Commun. 1202 (1988)
123

2406
N. Babakhani, S. Keshipoor
20. L.L. Andreani, E. Lapi, Boll. Chim. Farm. 99, 583 (1960)
21. L. Bonsignore, G. Loy, D. Secci, A. Calignano, Eur. J. Med. Chem. 28, 517 (1993)
22. E.C. Witte, P. Neubert, A. Roesch, Chem. Abstr. 104, 224915f (1986)
23. Y.L. Zhang, B.Z. Chen, K.Q. Zheng, M.L. Xu, L.Z. Zhang, X.H. Lei, Acta Pharm. Sin. 17, 17 (1982)
24. C.S. Konkoy, D.B. Fick, S.X. Cai, N.C. Lan, J.F.W. Keana, PCT Int. Appl. WO oo75123 (2000)
25. P. Li, L.L. Luo, X.S. Li, J.W. Xie, Tetrahedron 66, 7590 (2010)
26. W.B. Chen, Z.J. Wu, Q.L. Pei, L.F. Cun, X.M. Zhang, W.C. Yuan, Org. Lett. 12, 3132 (2010)
27. M.A. Khalilzadeh, Z. Hossaini, M.M. Baradarani, A. Hasanni, Tetrahedron 66, 8464 (2010)
28. A. Shaabani, A.H. Rezayan, A. Sarvary, A. Rahmati, H.R. Khavasi, Catal. Commun. 9, 1082 (2008)
123