Cu-Nanoparticles: efficient catalysts for the oxidative cyclization of Schiffs' bases

Article abstract of DOI:10.1016/j.tetlet.2006.09.066

Cu-Nanoparticles provide an efficient catalysis for the synthesis of 2-arylbenzoxazoles by the coupling of aromatic or heteroaromatic aldehydes with 2-aminophenol though the oxidative cyclization of the Schiffs' bases using 10 mol % of the Cu-nanoparticles in the presence of K₂CO₃ in MeOH. This method avoids the use of metal oxide or organic oxidizing agents, namely, DDQ or strong acids such as polyphosphoric acid or boric acid.

Full text of DOI:10.1016/j.tetlet.2006.09.066

Tetrahedron Letters 47 (2006) 8049–8053
Cu-Nanoparticles: efficient catalysts for the oxidative
cyclization of Schiffs’ bases
a,
a
b
b
b
*
Mazaahir Kidwai, Vikas Bansal, Amit Saxena, Swati Aerry and Subho Mozumdar
a
Green Chemistry Research Laboratory, University of Delhi, Delhi 110 007, India
b
Laboratory for Nanobiotechnology, University of Delhi, Delhi 110 007, India
Received 20 July 2006; revised 4 September 2006; accepted 15 September 2006
Available online 2 October 2006
Abstract—Cu-Nanoparticles provide an efficient catalysis for the synthesis of 2-arylbenzoxazoles by the coupling of aromatic or
heteroaromatic aldehydes with 2-aminophenol though the oxidative cyclization of the Schiffs’ bases using 10 mol % of the Cu-
nanoparticles in the presence of K
DDQ or strong acids such as polyphosphoric acid or boric acid.
2006 Elsevier Ltd. All rights reserved.
2 3
CO in MeOH. This method avoids the use of metal oxide or organic oxidizing agents, namely,
ꢀ
OH
O
N
OH
N
In recent years, there has been growing interest in the
catalytic properties of transition metal nanoparticles.
Y
Z
b
a
1
+
R
R
R
NH2
The high surface area-to-volume ratio of solid-sup-
2
ported metal nanoparticles (1–10 nm in size) is mainly
1
2
3
4
responsible for their catalytic properties and this can
3
Z = NH, O
Y = OH, OEt, Cl, F
be exploited in many industrially important reactions.
Recent literature shows that the application of nano-
particles as catalysts in organic synthesis has been little
explored. Cu-Nanoparticles, in particular, being cheap,
require only mild reaction conditions for high yields of
products in short reaction times as compared to
traditional catalysts.
Scheme 1. Retrosynthesis of 2-substituted benzoxazoles.
xylic acid or its derivative with 2-aminophenol with
dehydration catalyzed by strongly acidic conditions,
for example, using boric or polyphosphoric acid and
1
4
high reaction temperatures,
or using microwave-
Benz-fused azoles are an important class of compounds
and provide a common heterocyclic scaffold in biologi-
1
5
assisted reaction conditions. The methodology devel-
oped under strategy ‘b’ includes photochemical, oxida-
1
6
4
–9
cally active and medicinally significant compounds.
Benzoxazoles are found in a variety of natural prod-
1
7
18
tive and radical cyclization of phenolic Schiffs’ bases
derived from the condensation of 2-aminophenols and
aldehydes. In the latter reaction, various oxidants
1
0
11
ucts and are important targets in drug discovery
and also find applications in material science as photo-
1
9
20
21
22
such as PhI(OAc) , NiO , Ba(MnO ) , DDQ,
1
2
13
2
2
4 2
25
chromic agents and laser dyes.
ꢀ
2
3
24
þ
Mn(OAc)2, Pb(OAc)2 and Th ClO
have been
4
used. Other methods include Ru-catalyzed hydroamina-
The two most popular known strategies for synthesizing
-substituted benzoxazoles are summarized in Scheme 1.
2
6
tion of diynes with 2-aminophenols, degradative cycli-
zation of imines derived from trifluoromethyl aryl
2
2
7
ketones and 2-aminophenols under basic conditions
The literature methods are based on the approaches
listed ‘a’ and ‘b’. Route ‘a’ involves coupling a carbo-
2
8
and CuI catalyzed cyclization of ortho-haloanilides
using 1,10-phenanthroline as the ligand in DME.
However, most of these methodologies suffer drawbacks
such as lengthy procedures that require excess reagents
(PPTS/PPA, p-TsOH, SOCl /HF, PPh -DEAD, metal
Keywords: Cu-Nanoparticles; 2-Arylbenzoxazole; Schiffs’ bases; Oxi-
dative cyclization.
*
Corresponding author. Tel./fax: +91 11 27666235; e-mail:
kidwai.chemistry@gmail.com
2
3
catalyst/oxidizing agents), harsh reaction conditions
0040-4039/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.09.066

8050
M. Kidwai et al. / Tetrahedron Letters 47 (2006) 8049–8053
(
strongly acidic, high temperature) and toxic solvents
amounts of benzaldehyde using 2 equiv of K CO as
2 3
2
9
such as xylene and pyridine. Oxidants are required in
stoichiometric amounts relative to the substrate. There-
fore, the development of a simple, efficient, inexpensive
and nontoxic methodology is still needed for the synthe-
sis of 2-arylbenzoxazoles.
the base in the presence of 10 mol % of Cu-np in meth-
anol. The best results were obtained on treating 1 mmol
of 2-aminophenol with 1 mmol of benzaldehyde for 4 h
3
5
(Scheme 3).
To our delight, we observed the formation of 2-phenyl-
benzoxazole 3a in a 90% yield after 4 h. Another set of
control experiments was conducted without Cu-np
which led to the formation of the Schiff’s base. The iso-
lated Schiffs’ base was stirred with 10 mol % Cu-np in
the presence of K CO , which resulted in the desired
As a part of continuing efforts in our laboratory towards
3
0
the synthesis of bioactive compounds and the use of
3
1
nanoparticles in new synthetic methodology, we report
here on the synthesis of 2-arylbenzoxazoles using
Cu-nanoparticles (Cu-np) as the catalyst.
2
3
2
-phenylbenzoxazole 3a. To focus on the mechanistic
2
+
The reduction of Cu ions to Cu(0) in a reverse micellar
system was employed to prepare the copper nanoparti-
cles (Scheme 2).
behaviour of Cu-np, a similar experiment was carried
3
2–34
OH
O
N
Cu-np, K CO3
2
+
R-CHO
R
The sizes of Cu-nanoparticles prepared at W = 5 (the
water content parameter W is defined as the molar ratio
of water to surfactant concentration, W = [H O]/[sur-
0
MeOH, O , 1 atm,
2
NH2
80-100 oC
0
1
2a-j
3a-j
0
2
factant]) were confirmed as 10–17 nm through quasi
elastic light scattering data (QELS) (Fig. 1a) and trans-
mission electron microscopy (TEM) (Fig. 1b). Cu-
Nanoparticles prepared were round in shape and brown
in colour (colloidal state). The metallic nature of the
Cu(0)-nanoparticles was confirmed by a characteristic
UV absorption at k 580 nm for the particles dispersed
in cyclohexane.
OH
O
K CO , MeOH
2
3
R
o
R
O2, 1 atm, 80-100 C
N
N
H
Benzaldehyde was chosen as a representative aromatic
aldehyde to optimize the reaction parameters. Thus,
1
mmol of 2-aminophenol was treated with varying
Scheme 3. Synthesis of a library of 2-arylbenzoxazoles.
reverse micellar solution
containing Cu-nanoparticles
extraction
of
nanoparticles with
absolute ethanol
Reverse micelle-A containing CuSO (aq.)
4
N2 atmosphere
5 o
+
2
C
nanoparticles + surfactant
molecules
Reverse micelle-B containing N H (aq.)
2
2
washing of nano-
particles
absolute ethanol
4-5 times)
with
(
Cu-nanoparticles free
from surfactant
Scheme 2. Preparation of Cu-nanoparticles.
Figure 1. (a) QELS data of Cu-nanoparticles: plot of percentile population distribution versus size distribution in nanometers (nm). (b) TEM image
of the Cu-nanoparticles. The scale bar corresponds to 100 nm in the TEM image.

M. Kidwai et al. / Tetrahedron Letters 47 (2006) 8049–8053
8051
Table 1. Catalytic activity evaluation for the synthesis of
Table 2. Effect of size of the nanoparticles on the synthesis of
2-phenylbenzoxazole
a
a
2-phenylbenzoxazole
b
b
Entry
Cu-Nanoparticles
Time (h)
Yield (%)
Entry
Cu-Nanoparticles
Time (h)
Yield (%)
(
x mol %)
(10 mol %, x ± 2 nm)
1
2
3
4
5
0
8.0
4.0
3.5
2.0
1.5
0
90
90
92
96
1
2
3
4
8
20
30
60
5.5
4.0
2.5
9.0
87
90
86
68
10
20
30
50
a
Reaction conditions: 1.0 equiv of 2-aminophenol, 1.0 equiv of benz-
aldehyde, 2.0 equiv of K CO , 10 mol % Cu-np (x ± 2 nm); solvent,
MeOH; temperature, 80–100 ꢁC; O ; 1 atm.
2
a
Reaction conditions: 1.0 equiv of 2-aminophenol, 1.0 equiv of benz-
aldehyde, 2.0 equiv of K CO , x mol % Cu-np (18 ± 2 nm); solvent,
MeOH; temperature, 80–100 ꢁC; O
2
3
2
3
b
2
; 1 atm.
Isolated and unoptimized yields.
b
Isolated and unoptimized yields.
in situ which undergoes oxidative cyclization to give
-phenylbenzoxazole. On each occasion, the reaction
2
out under an inert atmosphere, which resulted in the for-
mation of the Schiffs’ base. It was concluded that the
condensation of 2-aminophenol with benzaldehyde in
the presence of Cu-np generates the Schiffs’ base
was monitored by thin layer chromatography.
With this positive result in hand further investigations
were carried out to establish the optimum reaction
a
Table 3. Cu-Nanoparticle promoted synthesis of a library of arylbenzoxazoles
b
Entry
Aldehyde
Product
Time (h)
3.0
Yield (%)
O
1
2a
2b
CHO
3a
3b
90
N
O
2
3
4
5
Cl
CHO
Cl
4.7
3.6
4.5
4.6
87
92
83
75
N
O
N
2c
2d
2e
MeO
CHO
3c
3d
3e
OMe
CH3
NO2
O
N
H C
3
CHO
CHO
O
N
O N
2
MeO
MeO
OMe
OMe
OMe
O
N
6
2f
CHO
3f
1.5
95
MeO
CHO
O
N
7
8
9
2g
2h
2i
3g
3h
3i
3.2
3.0
4.8
5.0
86
74
69
O
O
O
O
O
CHO
N
O
S
CHO
S
N
O
N
O
1
0
2j
3j
71
CHO
O
a
Reaction conditions: 1.0 equiv of 2-aminophenol, 1.0 equiv of aromatic/heteroaromatic aldehyde, 2.0 equiv of K
20 ± 2 nm); solvent, MeOH; temperature, 80–100 ꢁC; O ; 1 atm.
2
3
CO , 10 mol % Cu-np
(
2
b
Isolated and unoptimized yields.

8052
M. Kidwai et al. / Tetrahedron Letters 47 (2006) 8049–8053
conditions. Increasing the amount of Cu-np up to
0 mol % not only enhanced the product yields but also
Supplementary data
5
reduced the reaction time (Table 1).
Supplementary data associated with this article can
be found, in the online version, at doi:10.1016/j.tetlet.
2006.09.066.
In order to evaluate the efficacy of Cu-np as a catalyst,
the reaction of 2-aminophenol with benzaldehyde was
carried out in various solvents such as methanol, aceto-
nitrile, toluene, dichloromethane and xylene. However,
the only product obtained was 2-phenylbenzoxazole
and methanol was the solvent of choice in terms of a
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3
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(IR, H, C NMR and mass spectral data). All the
products are known compounds. (See Supplementary
data.)