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R. Shelkar et al. / Tetrahedron Letters 54 (2013) 6986–6990
Table 2
Optimization of various parameters for model reactions
Entry
Nano CeO2 (mol %)
Time (min)
Yielda (%)
1a
2a
3a
1
2
3
4
5
6
0
2
5
10
5
5
20
20
20
20
10
30
<20
67
88
89
79
92
41
79
96
98
87
97
36
74
95
97
80
95
a
Isolated yield.
Table 3
Recyclability of nano CeO2 in catalyzing the model reactions
Entry
No. of cycles
Yielda (%)
1a
2a
3a
1
2
3
4
0
1
2
3
92
90
86
81
96
93
89
87
95
91
88
84
a
Isolated yield.
screened a variety of catalysts for the model reactions such as ZnO,
TiO2, MnO2, SiO2, CeO2, La2O3, Al2O3, nano Cu2O, and nano ZnO and
the results are summarized in Table 1. The results clearly indicate
that nano CeO2 is superior to other catalysts due to the smaller par-
ticle size and high surface area.
results than the electron donating substituents such as –OH,
–OCH3, –N(CH3)2, –CH3, –F, –Cl, and –Br. Furthermore the reactiv-
ity of these substituent does varies according to their position on
the benzene ring of benzaldehyde. The electron-withdrawing sub-
stituents gave better product yield at 4 and 2 position of the ben-
zene ring as compared to 3 position (Table 4, entries 12–15, 33–36,
and 56–59). While electron-donating ones at these positions gave
variable product yields (Table 4, entries 2–11, 24–32, and 47–
55). This variation in product yields with nature and position of
substituents may be due to resonating, inductive and sterric ef-
fects. We also tried aromatic disustituted aldehydes 3,4-difluoro,
3,5-difluoro, 3,4-dimethoxy, and 2-methoxy-5-bromo benzalde-
hyde and obtained good yield of the corresponding products (Ta-
ble 4, entries 16, 17, 37–39, and 60–62). The heteroaromatic
aldehydes such as furfural aldehyde, pyrrol-2-aldehyde, and pyri-
dine-3-aldehyde have given moderate to good yields of their
respective products under similar reaction conditions (Table 4, en-
tries 18–20, 40–42 and 63–65).
The model reactions were optimized for catalyst concentration
and time. The results are shown in Table 2. 5 mol % of nano CeO2
was sufficient for maximum product yields (Table 2, entry 3). An
increment in catalyst concentration more than 5 mol % did not
show effective increase in product yields (Table 2, entry 4). The
reactions proceeded without catalyst but with lower yields,
whereas 2 mol % catalyst loading gave fairly good yields (Table 2,
entries 1 and 2). This clearly indicates that in the absence of cat-
alyst, reaction did not work beneficially. We also found out the
time required to complete the reaction (Table 2, entries 3, 5,
and 6). The required time would be 30, 20, and 20 min to get
excellent yield of products for the completion of Schemes 1–3
respectively.
Recyclability of the catalyst is an important task in industrial
applications. Therefore reusability of nano CeO2 was investigated
for three cycles (Table 3, entries 1–4). The reaction mixture was di-
luted with ethyl acetate and subsequently centrifuged to get the
catalyst. The obtained nano CeO2 was then washed with acetone
followed by drying in oven at 150 °C for 12 h. The recovered cata-
lyst was then used for the next batch of reactions. It was found that
the reactivity of the catalyst decreases marginally for the next cy-
cle (approx 4%).
Nano CeO2 also showed good catalytic activity with aliphatic
aldehydes such as propionaldehyde (Table 4, entries 21, 44, and
67). In this substrate study we also screened a,b-unsaturated aro-
matic aldehydes such as cinnamaldehyde which gave good re-
sponse to synthesize these heterocycles (Table 4, entries 22, 45,
and 68).
In case of Scheme 1, The reaction of 1,2-phenylenediamine and
benzaldehyde in 1:2 ratio gave only 1,2-disubstituted benzimidaz-
oles whereas when this ratio was changed to 1:1 then 2-substi-
tuted benzimidazole was obtained with 98% product yield under
same reaction conditions (Figs. 3–5).
The scope and applicability of the catalyst in the formation of
functionalized heterocycles were investigated by using various
aromatic, heteroaryl, aliphatic, and
a
,b-unsaturated aldehydes un-
In conclusion, we developed an efficient, selective, and green
route by using nano CeO2 to synthesize variety of 1,2-disubstituted
benzimidazoles, 2-substituted benzothiazoles, and 2-substituted
benzoxazoles from 1,2-phenylenediamine, 2-aminothiophenol,
and 2-aminophenol with aromatic as well as aliphatic aldehydes.
All these reactions are feasible at room temperature and in aque-
ous medium. In case of catalyst concentration, 5 mol % of CeO2
gave a better yield of products. Aromatic aldehydes have given a
der the same reaction conditions. The results are summarized in
Table 4. In the synthesis of 1,2-disubstituted benzimidazoles, ben-
zothiazoles, and benzoxazoles excellent yield of products have
been obtained with aromatic aldehydes. The nature and position
of the substituents on the benzene ring of aromatic aldehydes have
shown some effect on the yield of the corresponding products. The
electron-withdrawing substituents like –NO2 and –CN gave better
Shelkar, Radheshyam
