Synthesis of some new 2-(3-aryl-1-phenyl-4-pyrazolyl)benzoxazoles using hypervalent iodine mediated oxidative cyclization of schiff's bases

Article abstract of DOI:10.3390/11010043

Ten new 2-(3-aryl-1-phenyl-4-pyrazolyl)benzoxazoles have been synthesized by oxidative intramolecular cyclization of the corresponding Schiff's bases using iodobenzene diacetate in methanol as an oxidant.

Full text of DOI:10.3390/11010043

Molecules 2006, 11, 43-48
molecules
ISSN 1420-3049
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Synthesis of Some New 2-(3-Aryl-1-phenyl-4-pyrazolyl)-
benzoxazoles Using Hypervalent Iodine Mediated Oxidative
Cyclization of Schiff’s Bases
*
Om Prakash , Kamaljeet Pannu and Ajay Kumar
Department of Chemistry, Kurukshetra University, Kurukshetra, Haryana 136 119, India.
*
Author to whom correspondence should be addressed; Fax: (+91) 1744 238277; e-mail:
dromprakash50@rediffmail.com
Received: 10 November 2004; in revised form: 6 July 2005 / Accepted: 6 July 2005 / Published:
31 January 2006
Abstract: Ten new 2-(3-aryl-1-phenyl-4-pyrazolyl)benzoxazoles have been synthesized
by oxidative intramolecular cyclization of the corresponding Schiff’s bases using
iodobenzene diacetate in methanol as an oxidant.
Keywords: Hypervalent iodine; Iodobenzene diacetate; Schiff’s base; Oxidation;
Benzoxazoles.
Introduction
In connection with our ongoing programme directed towards the use of organoiodine(III)
compounds as unique reagents in organic synthesis [1-2], we have recently reported that oxidation of
phenolic Schiff’s bases (SBs) with iodobenzene diacetate (IBD) leads to facile intramolecular
cyclization, thus providing an efficient synthesis of 2-substituted benzoxazoles (Scheme 1) [3]. This
observation, coupled with the fact that benzoxazoles [4] and pyrazoles [5] are often associated with
important biological properties, prompted us to extend the scope of this iodine(III) mediated approach
to the synthesis of some new 2-(3-aryl-1-phenyl-4-pyrazolyl)benzoxazoles 4aa-4be.

Molecules 2006, 11
44
Scheme 1
AcO
I
Ph
N
Ar
N
O
N
PhI(OAc)
2
Ar
X
Ar
X
O
H
OH
Results and Discussion
First we prepared Schiff’s base 3aa by the condensation of o-aminophenol (1a) with 4-formyl-1,3-
diphenylpyrazole (2a). Then, oxidation of 3aa was tried using our previously reported procedure
involving 1.1 equivalents of IBD in dichloromethane. The reaction occurred readily, but the yield of
the expected product 4aa was not good (only 24%). Interestingly, using methanol as a solvent in this
reaction, compound 4aa was obtained in noticeably improved yield (60%). In order to study the scope
of this approach, other Schiff’s bases 3aa-3be, available by the condensation of 1a or 1b with different
formylpyrazoles 2a-e, were subjected to oxidative cyclization using 1.1 equivalents of IBD in
methanol. The reaction, indeed, afforded the desired benzoxazole derivatives 4aa-4be in yields
ranging from 55% to 88% (Scheme 2, Table 1).
Scheme 2
Ph
N
Ph
N
X
NH2
OH
X
N
N
N
EtOH
+
OH
CHO
Y
1
2
3
Y
1
a
b
X
H
2
a
b
c
Y
H
3, 4
aa
ab
ac
X
H
H
H
H
H
Cl
Cl
Y
H
X
Ph
N
O
N
N
PhI(OAc)2
MeOH
Cl
Cl
Cl
OMe
Me
OMe
Me
d
e
ad
ae
NO
2
NO
H
2
ba
bb
bc
bd
be
Y
Cl
4
Cl OMe
Cl
Cl
Me
NO
2

Molecules 2006, 11
45
The formylpyrazoles 2a-e needed in this study were prepared by Vilsmeier-Haack reaction of
acetophenone phenylhydrazones (Scheme 3) [6]. The formylpyrazoles 2a and 2e are known
compounds [6] and were identified by comparison of their melting points with those reported in the
literature. The products 2b-2d are new compounds and were characterized by their spectral data.
The products 3aa-3be and 4aa-4be are also all new compounds and their structures were
established by spectral and elemental analysis data. Schiff’s bases 3aa-3be were characterized by the
-
1
-1
absence of the 1674 cm (C=O stretch) signal and presence of a broad weak signal at 3360 cm (O-H
1
stretch) in their IR spectra. A distinctive feature of their H-NMR spectra was presence of two singlets
5
between 8.3 δ- 8.8 δ corresponding to the C -H and CH=N protons (Table 2). The intramolecular
cyclization of Schiff’s bases to 2-(3-aryl-1-phenyl-4-pyrazolyl)benzoxazoles 4aa-4be was
-
1
characterized by the disapperance of the 3360 cm (O-H stretch) signal in the IR spectra, a downfield
shift of the C
5
-H proton as a result of the cyclization and the disappearance of the CH=N proton signal
1
in the corresponding H-NMR spectra (Table 2).
Scheme 3
NNHPh
Ph
N N
CH3
POCl -DMF
3
°
50-60 C
Y
Y
CHO
2
Conclusions
In summary, the synthesis of new pyrazolylbenzoxazoles reported in this study provides a novel
example of an attractive and effective iodine(III) mediated heterocyclic synthesis. The organoiodine
(
III) mediated approach described is preferred over the existing methods because of the less toxic
nature of these reagents compared to other oxidants previously used in this type of transformation,
namely, lead tetraacetate [7], nickel peroxide [8], copper (I) chloride in the presence of dioxygen [9],
which are highly toxic.
Acknowledgements
We are thankful to Kurukshetra University, Kurukshetra, for the award of a University Research
Fellowship to Kamaljeet Pannu and to DRDO (ERIP/ER/0103294/M/01), New Delhi, for the award of
a Senior Research Fellowship to Ajay Kumar to carry out this work.
Experimental
General
All reagents were purchased from commercial sources and were used without further purification.
1
Melting points were taken in open capillaries and are uncorrected. H-NMR spectra were recorded on a

Molecules 2006, 11
46
Bruker 300 MHz instrument using TMS as an internal standard. IR spectra were recorded on a Buck
Scientific IR M-500 spectrophotometer. Yields, physical properties (m.p.) and spectroscopic data of
the prepared compounds are summarized in Tables 1 and 2.
General Method for the Preparation of 3-Aryl-4-formyl-1-phenylpyrazoles 2a-e:
The appropriate acetophenone phenylhydrazone (15 mmol) was added to a cold solution of
dimethylformamide (25 mL) and phosphorus oxychloride (5 mL), and the resulting mixture was stirred
at 50-60 °C for 5-6 hrs, then cooled to room temperature and poured into ice-cold water. A saturated
solution of sodium bicarbonate was added to neutralize the mixture and thus give formylpyrazoles
2
a-e, which were isolated by filtration, followed by washing with water. 2a: M.p. 137-138 °C, (Lit. [6]
°
1
m.p. 140 C); 2b: M.p. 110-113 °C, H-NMR (CDCl
H, C -H), 9.96 (s, 1H, CHO). IR (νmax, KBr): 1674 cm (C=O); 2c: M.p. 100-102 °C, H-NMR
CDCl ) δ: 3.83 (s, 3 H, OCH ), 6.7-7.1 (m, 9 H, aromatic protons), 8.46 (s, 1 H, C -H), 9.98 (s, 1 H,
CHO). IR (νmax, KBr): 1678 cm (C=O); 2d: M.p. 120-122 °C, H-NMR (CDCl ) δ: 1.5 (s, 3 H, CH ),
.8-7.6 (m, 9 H, aromatic protons), 8.57 (s, 1 H, C -H), 9.87 (s, 1 H, CHO). IR (νmax, KBr): 1680 cm
C=O); 2e: 163-164 °C, (Lit. [6] m.p. 165 °C).
3
) δ: 6.9- 7.2 (m, 9 H, aromatic protons), 8.5 (s,
-
1
1
1
5
(
3
3
5
-
1
1
3
3
-
1
6
5
(
General Method for the Synthesis of Schiff’s bases (SBs) 3aa-3be:
SBs were prepared by refluxing a solution of the appropriate formylpyrazole 2a-e (20 mmol) and
o-aminophenol/p-chloro-o-aminophenol (1a-b, 30 mmol) in ethanol (100 mL) for 45-60 minutes. The
solid product thus obtained was filtered off and recrystallised from ethanol. The physical and spectral
data of the products are listed in Table 2.
General Method for the Synthesis of 2-(3-aryl-1-phenyl-4-pyrazolyl)benzoxazoles 4aa-4be from 3aa-
3
be:
To a solution of the appropriate Schiff’s base 3aa-be (10 mmol) in methanol (10 mL) was added
IBD (11 mmol) and the mixture was stirred for 45-50 minutes at room temperature. The solid
separated was filtered off and washed with methanol. The crude product thus obtained was
recrystallized from ethanol. The physical and spectral data of the pure products are listed in Table 1.
1
Table 1. Physical and H-NMR data of
2-(3-aryl-1-phenyl-4-pyrazolyl)benzoxazoles 4aa-4be
b
m.p.
°C)
Yield
(%)
60
a
1
Comp.
H-NMR (δ)
(
4
aa
ab
ac
141-142
186-187
166-168
6.84-7.84 (m, 14 H, aromatic protons), 8.65 (s, 1 H, C
7.34-8.05 (m, 13 H, aromatic protons), 8.74 (s, 1 H, C
5
-H)
-H)
4
81
5
4
64
3.89 (s, 3 H, OCH
-H)
3 5
1.5 (s, 3 H, CH ), 7.18-7.94 (m, 13 H, aromatic protons), 8.53 (s, 1 H, C -H)
3
), 7.02-7.99 (m, 13 H, aromatic protons), 8.71 (s, 1 H,
C
5
4ad
142-145
58

Molecules 2006, 11
47
Table 1. Cont.
b
m.p.
Yield
(%)
61
a
1
Comp.
H-NMR (δ)
(
°C)
4
ae
ba
bb
bc
122-124
137-139
160-161
128-129
7.19-8.21 (m, 13 H, aromatic protons), 8.65 (s, 1 H, C
7.22-7.92 (m, 13 H, aromatic protons), 8.65 (s, 1 H, C
5
-H)
-H)
4
73
5
4
78
7.20-7.93 (m, 12H, aromatic protons), 8.63 (s, 1H, C
3.83 (s, 3 H, OCH ), 6.94-7.9 (m, 12 H, aromatic protons) 8.63 (s, 1 H,
-H)
5
-H)
4
72
3
C
5
4
bd
148-150
55
76
3 5
1.5 (s, 3 H, CH ), 6.81-7.93 (m, 12 H, aromatic protons), 8.65 (s, 1 H, C -H)
4
be
240-242
c
a
These are new products and their obtained elemental analyses (C, H, N) were satisfactory.
Yields of isolated pure product based on the amount of Schiff’s base employed.
b
c 1
H-NMR could not be recorded because of solubility problems.
Table 2. Physical and spectral data of Schiff’s bases 3aa-3be
b
m.p.
°C)
Yield
(%)
76
IR (O-H
a
1
Comp.
aa
ab
ac
H-NMR (δ)
-1
(
str cm )
3
143-144
142-143
146-147
126-128
100-101
182-183
240-242
128-129
160-162
3351
6.84-7.84 (m, 14 H, aromatic protons), 8.60 (s, 1 H, C
s, 1 H, HC=N)
6.98-7.84 (m, 13 H, aromatic protons), 8.58 (s, 1 H, C
s, 1 H, HC=N)
3.89 (s, 3 H, OCH
s, 1 H, C -H), 8.71 (s, 1 H, HC=N)
1.5 (s, 3 H, CH ), 7.18-7.94 (m, 13 H, aromatic protons), 8.42 (s,
H, C -H), 8.65 (s, 1 H, HC=N)
7.19-8.21 (m, 13 H, aromatic protons), 8.52 (s, 1 H, C
s, 1 H, HC=N)
6.89-7.77 (m, 13 H, aromatic protons), 8.52 (s, 1 H, C
s, 1 H, HC=N)
7.20-7.93 (m, 12 H, aromatic protons), 8.54 (s, 1 H, C
s, 1 H, HC=N)
3.83 (s, 3 H, OCH
s, 1 H, C -H), 8.59 (s, 1 H, HC=N)
1.5 (s, 3 H, CH ), 6.81-7.93 (m, 12 H, aromatic protons), 8.53 (s,
-H), 8.62 (s, 1 H, HC=N)
5
-H), 8.73
(
3
72
81
58
61
78
79
72
55
86
3390
3375
3348
3345
3360
3359
3372
3358
3414
5
-H), 8.69
(
3
3
), 7.02-7.99 (m, 13 H, aromatic protons), 8.58
(
5
3ad
3
1
5
3
ae
ba
bb
5
-H), 8.64
5
-H), 8.59
5
-H), 8.66
(
3
(
3
(
3bc
3
), 6.94-7.9 (m, 12 H, aromatic protons), 8.47
(
5
3
bd
3
1
H, C
5
3be
252-254
c
a
These are new products and their obtained elemental analyses (C, H, N) were satisfactory.
Yields of Schiff’s bases based on the amount of formylpyrazole used.
b
c 1
H-NMR could not be recorded due to poor solubility.

Molecules 2006, 11
48
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