Nano-tube TiO2 as a new catalyst for eco-friendly synthesis of imines in sunlight

Article abstract of DOI:10.1016/j.cclet.2010.11.017

Nanomaterials are considered as suitable heterogeneous catalysts for many organic reactions. Herein nano-tube TiO₂ has been reported as a heterogeneous catalyst, for synthesis of imines in sunlight at room temperature under solvent-free conditions. The condensation of less electrophilic carbonyl compounds with poorly nucleophilic amines was afforded imines in excellent yields.

Full text of DOI:10.1016/j.cclet.2010.11.017

Available online at www.sciencedirect.com
Chinese Chemical Letters 22 (2011) 547–550
www.elsevier.com/locate/cclet
Nano-tube TiO2 as a new catalyst for eco-friendly
synthesis of imines in sunlight
Mona Hosseini-Sarvari
Department of Chemistry, Shiraz University, Shiraz 71454, Iran
Received 30 August 2010
Available online 2 March 2011
Abstract
Nanomaterials are considered as suitable heterogeneous catalysts for many organic reactions. Herein nano-tube TiO2 has been
reported as a heterogeneous catalyst, for synthesis of imines in sunlight at room temperature under solvent-free conditions. The
condensation of less electrophilic carbonyl compounds with poorly nucleophilic amines was afforded imines in excellent yields.
# 2010 Mona Hosseini-Sarvari. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Nano-tubes; TiO2; Imines; Solvent-free; Sunlight
The nitrogen atom is present in many natural products, biologically important molecules, pharmaceuticals, and
dyes [1]. Imines and their derivatives are useful intermediates in organic synthesis [2,3], in particular for the
preparation of heterocyclic and non-natural b-amino acids [4–7]. Several methods for synthesis of imines were
described in the literature [8–12]. However, these methodologies suffer from disadvantages such as complex
procedures, long reaction times, high reaction temperatures, moisture sensitive catalysts, and using aromatic solvents.
Moreover, reported procedures are often limited to the reaction of highly electrophilic carbonyl compounds and
strongly nucleophilic amines. Solvent-free synthesis of imines and enamines under microwave irradiation has been
also described [13], but this method applied to a limited number of compounds and the probability of scaling up was
not evaluated. Recently, Stefany et al. [14] reported the synthesis of imines using ultrasound irradiation in EtOH as
solvent and Chakraborti et al. [15] also reported magnesium perchlorate as the catalyst for such reaction but
perchlorates are potentially explosive [16].
Nano-scale materials have attracted great interest because of their novel properties, which are different from those
of bulk materials. Materials with nano-sized tubular structures including carbon, metal sulfides and metal oxides have
been developed [17]. Among the nano-structured oxides, TiO2 has been a focus of extensive research due to its
chemical stability, large surface area, non-toxicity, and low production cost [18]. Titania nano tubes showed their
potential in many fields, such as photo catalysis [19–21], hydrogen sensing [22], and solar cells [23]. TiO2 is a well-
known n-type semiconductor with high photo catalytic activity and widely used as a catalyst or catalyst support [24].
Recently, Knoevenagel condensation has been reported by using bulky TiO2 as catalyst [25]. So, in continuation of our
interest in exploring the synthetic utility of nano metal oxides [26], especially TiO2, the condensation of carbonyl
E-mail addresses: hossaini@susc.ac.ir, hossaini@shirazu.ac.ir.
1001-8417/$– see front matter # 2010 Mona Hosseini-Sarvari. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2010.11.017

548
M. Hosseini-Sarvari / Chinese Chemical Letters 22 (2011) 547–550
compounds with amines to form imines is reported. Nano-tube TiO2 with define shapes and sizes can be easily
prepared by a previous reported method [27].
1. Experimental
A mixture of nanotube-TiO2 (10 mol%, 0.008 g), amine (1 mmol) and aldehyde (1 mmol) were mixed in a Petri
dish. The mixture was placed on the lab bench under sunlight. The progress of the reaction was monitored by 1H NMR
or TLC. After the reaction was completed, EtOAc (2 Â 20 mL) was added to the reaction mixture and the catalyst
separated by centrifugation. The organic solvent was removed under reduced pressure to afford the respective imines.
The crude products were purified by column chromatography (eluent: 95:5 hexane–EtOAc). NMR, IR, and mass
spectra confirmed the structure of the products that compared with authentic samples obtained commercially or
prepared by reported methods. Most of the compounds are known and their analytical data were previously reported in
the literature. The procedure for recovery of the catalyst is as follows: a mixture of 4-chlorobenzaldehyde (1e,
1 mmol), aniline (2a, 1 mmol) and nano-tube TiO2 (10 mol%) was placed in a Petri dish at room temperature under
sunlight for 5 min. Then EtOAc was added to the reaction mixture, centrifuged until the catalyst was deposited at the
bottom of centrifuge tube. The deposited catalyst was washed with EtOAc 2–3 times to complete removal of organic
residues, dried in an oven at 100–120 8C for 5–6 h and then the catalyst was re-used for the same reaction. 5-
(Morpholinomethyl)2-2[(phenylimino)methyl]phenol (3m): Pale yellow, crystalline solid; mp 164–166 8C; IR (KBr)
1
nmax (cmÀ1): 3639, 2863, 1652 (C N); H NMR (CDCl3, 250 MHz): d 13.1 (s, 1H, –OH), 8.85 (s, 1H, –CH N–),
7.17–7.58 (m, 7H, ArH), 6.84–6.94 (m, 1H, Ar–H), 3.63 (m, 4H, –O–CH2–), 3.38 (s, 2H, –CH2–), 2.37 (m, 4H, –N–
CH2–); 13C NMR (CDCl3, 62.9 MHz): d 162.5, 160.0, 147.6, 134.2, 132.8, 129.9, 128.8, 126.9, 121.1, 118.5, 117.1,
115.1, 66.8, 62.5, 53.4 (some peaks were overlapped); Anal. calcd. for C18H20N2O2: C, 72.95; H, 6.80. Found: C,
72.90, H, 6.76. N-[1-(4-Methoxyphenyl)methylidene]-N-(2-pyridylmethyl)aniline (3z): yellow crystalline solid; mp
1
89–91 8C; IR (KBr) nmax (cmÀ1): 1661 (C N); H NMR (CDCl3, 250 MHz): d 8.58 (s, 1H, Ar–H), 8.36 (s, 1H, –
CH N–), 6.75–7.74 (m, 7H, ArH), 4.89 (s, 2H, –CH2–), 3.76(s, 3H, –OMe); 13C NMR (CDCl3, 62.9 MHz): d 162.4,
161.9, 158.0, 148.2, 136.0, 135.1, 129.8, 124.0, 122.2, 113.7, 66.6, 55.0 (some peaks were overlapped); Anal. calcd.
for C14H14N2O: C, 74.31; H, 6.24. Found: C, 74.29, H, 6.20.
2. Results and discussion
With the aim of improving the synthesis of imines, a systematic study of the reaction between carbonyl compounds
and amines by using nano tube-TiO2 as catalyst in sunlight as an alternative energy source was studied (Scheme 1).
The condensation between a carbonyl compound and an amine leading to the formation of an imine should be a
facile reaction due to the good electrophilic and nucleophilic properties of the carbonyl and amine groups,
respectively. This condensation may not require any catalytic assistance in the absence of electronic/steric factors that
might decrease the electrophilicity/nucleophilicity of the carbonyl/amine groups. The presence of the methoxy group
in 4-methoxybenzaldehyde reduces the electrophilicity of the carbonyl carbon through resonance and the strong
electron withdrawing properties of the nitro group in 4-nitroaniline decreases the nucleophilicity of the amine group.
Thus, the combination of these substrates constitutes a model reaction for evaluating the efficiency of a catalyst.
Hence, 4-methoxybenzaldehyde was treated with 4-nitroaniline under various conditions (Table 1).
As can be seen in Table 1, the best results were achieved with nanotube-TiO2 in sunlight (entry 1). To establish the
scope of nano-tube TiO2 as a catalyst for the synthesis of imines, structurally diverse carbonyl compounds were treated
with various amines. The results are summarized in Table 2. Excellent results were obtained in most cases.
As shown in Table 2, a wide range of aromatic and heteroaromatic aldehydes and amines bearing electron-donating
and withdrawing substituents were employed and all imines were obtained in excellent yields (entries 1–28). The
reaction worked very well with ortho and meta substituted aromatic aldehydes. In contrast, ortho and meta substituted
[()TD$FIG]
NR3
R2
O
nano-tube TiO2 (10 mol%)
sunlight, r.t.
R3NH2
+
+ H2O
R1
R2
R1
1
2
3
Scheme 1. General systematic study.

M. Hosseini-Sarvari / Chinese Chemical Letters 22 (2011) 547–550
549
Table 1
Reaction between 4-methoxybenzaldehyde (1d) and 4-nitroaniline (2b) in the presence of various catalysts.
Entry
Catalyst/conditions
Time
Yield (%)a
b
1
2
3
4
5
6
7
Nanotube-TiO2 (10 mol%)/neat/sunlight
8 h
98
Nanotube-TiO2 (10 mol%)/CH2Cl2/sunlightc
Nanotube-TiO2 (10 mol%)/PhMe/sunlight
Nanotube-TiO2 (10 mol%)/THF/sunlightc
Nanotube-TiO2 (10 mol%)/neat/dark
No catalyst/neat/sunlight
1 week
1 week
1 week
1 week
1 week
50 h
Trace
Trace
Trace
0
0
d
Commercial TiO2 (10 mol%)/neat/sunlight
85
a
Yields are the isolated compounds.
Samples of nano-tube prepared TiO2 (SA: ꢀ200 m2/g, 9–10 nm with the inner diameter of around 5–6 nm), [27] was synthesized as reported in
b
the literature.
c
The Petri dish was wrapped with Para-film and the solvent was added continually.
Commercial TiO2 (SA: ꢀ5 m2/g, with particles crystal shape) was purchased from Fluka no. 89490.
d
Table 2
Nano-tube TiO2 catalyzed imines synthesis under solvent free conditions.
Entry
R1
R2
R3
Imines
Time
Yielda (%)
1
2
3
4
5
C6H5 1a
H
H
H
H
H
C6H5 2a
3a
3b
3c
3d
3e
1 h
98
4-OH–C6H4 1b
4-NO2–C6H4 1c
4-OMe–C6H4 1d
4-Cl–C6H4 1e
2a
2a
2a
2a
10 min
7 min
10 min
5 min
98
98
98
98(1st use), 98 (2nd use),
95 (3rd use), 95 (4th use),
94 (5th use)
6
7
4-Me–C6H4 1f
2-Cl–C6H4 1g
3-Cl–C6H4 1h
3-Me–C6H4 1i
3-Thionyl 1j
2-Furyl 1k
H
H
H
H
H
H
H
2a
2a
2a
2a
2a
2a
2a
3f
3g
3h
3i
15 min
48 h
98
95
90
90
95
98
98
8
48 h
9
48 h
10
11
12
3j
3k
3l
48 h
24 h
4-Pyridinyl 1l
5 min
13
H
2a
3m
24 h
90
[TD$INLINE]
14
15
16
17
18
19
20
21
22
23
24
25
Cyclohexyl 1n
C6H5 1o
C6H5 1p
2a
2a
3n
3o
3p
3q
3r
3s
6 h
98
95
95
98
98
98
98
95
98
95
98
98
C6H5CH CH–
CH3
1 h
2a
12 h
1d
1d
1d
1d
1d
1d
1d
1d
1d
4-NO2–C6H4 2b
4-MeO–C6H4 2c
4-Me–C6H4 2d
4-CN–C6H4 2e
3-HO–C6H4 2f
3-MeO–C6H4 2g
3-Br–C6H4 2h
2-HO–C6H4 2i
2-HO–5-Me–C6H3 2j
8 h
30 min
10 min
8 h
3t
3u
3v
3w
3x
3y
10 min
3 h
24 h
10 min
5 min
26
1d
3z
6 h
98
[DT$INLE]
27
28
1d
1d
HOCH2CH2CH2 2l
CH3CH2CH2 2m
3aa
3ab
12 h
6 h
95
90
a
Isolated yields.

550
M. Hosseini-Sarvari / Chinese Chemical Letters 22 (2011) 547–550
aromatic aldehydes such as ortho-chlorobenzaldehyde (1g) and meta-chlorobenzaldehyde (1h) gave slightly lower
yields than para substituted aldehydes, even when the reaction time was increased to 48 h (entries 7, 8). In these cases,
no significant imine formation was observed under neat conditions after 1 week at room temperature. Ketones were
also tested (entries 14–16) under these reaction conditions and the corresponding imine products were obtained in
excellent yield, however, most of the other catalysts which was reported previously in the literature were not useful for
the reaction between ketones and amines [10]. Concerning primary amines, aromatic amines were used as well as
aliphatic amines and as can be seen in Table 2, no difference, in the reactivity was observed. All imines were obtained
in a very high yield and in some cases quantitative yields were achieved (entries 17–28). The reusability of the catalyst
was checked over five cycles. As shown in Table 2, Entry 5, the yields of 3e in second, third, forth, and fifth uses of the
catalyst were almost same as that in the first use.
In summary, it is shown that nanotube-TiO2 is a highly active catalyst for the synthesis of imines in good to
excellent yields. The title compounds are of chemical and medicinal interest. Among the advantages of the method that
can be mentioned are: (i) the reaction is simple to execute; (ii) the yields are excellent (>95%); (iii) the procedure dose
not require specialized equipment; (iv) a very simple work-up and (v) solvent-free condition.
Acknowledgments
We thank the Shiraz University Research Council, and the Iran National Science Foundation (No. 87040564) for
financial support.
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