Synthesis of some novel 2-substituted-N-aryl-benzoxazole-5-carboxamides using cobalt dipyridine dichloride as a catalyst

Article abstract of DOI:10.1002/jhet.5570450439

(Chemical Equation Presented) An efficient synthesis of some novel 2-substituted-N-aryl-benzoxazole-5-carboxamides from 2-substituted - 5-carbomethoxy benzoxazole on treatment with different substituted anilines promoted by cobalt dipyridine dichloride as a catalyst is described. This new approach has the advantage of excellent yields (90%) and short reaction times 1-2 h.

Full text of DOI:10.1002/jhet.5570450439

Jul-Aug 2008
1187
Synthesis of some Novel 2-Substituted-N-Aryl-Benzoxazole-5-
Carboxamides using Cobalt Dipyridine Dichloride as a Catalyst
M. Sarangapania*, D. Sridhar b, M. Arjunb, M. Adharvana Charic
a) University College of Pharmaceutical Sciences, Kakatiya University, Warangal, India.
b) Department of Chemistry, Kakatiya University, Warangal, India, 506009.
c) Department of Chemistry, Kyung Hee University, South Korea.
drmac_s@yahoo.com
Received February 8, 2007
O
O
O
O2N
HO
OCH3
H2N
HO
OCH3
Al(NO3)3
OCH3
Na2S2O4
AcOH + Ac2O
HO
3
1
2
RCOOH
R1
O
O
CoPy2Cl2
MeOH
NH2
NH
OCH3
N
O
N
R
R
O
5
4
R1
Reflux
An efficient synthesis of some novel 2-substituted-N-aryl-benzoxazole-5-carboxamides from 2-
substituted – 5-carbomethoxy benzoxazole on treatment with different substituted anilines promoted by
cobalt dipyridine dichloride as a catalyst is described. This new approach has the advantage of excellent
yields (90%) and short reaction times 1-2 h.
J. Heterocyclic Chem., 45, 1187 (2008).
INTRODUCTION
hydride, sodium metal, butyl lithium, potassium amide,
Grignard reagents, silicon tetrachloride, boron tribromide
and 2-pyridone, although their broader utility has not been
established. The direct synthesis of amides by the reaction
of the appropriate amine and either an acid chloride or
anhydride is a well-known organic synthetic procedure.
Amides and some substituted amides from primary
aliphatic amines can be prepared by direct aminolysis. In
general aromatic amines will not undergo this conversion.
The use of a trace of sodium methoxide as a catalyst for
the ammonolysis of esters is well known.
Benzoxazole compounds are an important class of
heterocyclic compounds having anti-inflammatory [1-2],
anticancer [3], and antimicrobial [4-5] activities.
Benzoxazoles possess a wide range of pharmacological
activities. Benzoxazoles containing an amide moiety at
position 5 are not known so far. In order to get more
potent compounds by combining biodynamic moieties, it
is planned to synthesize some novel benzoxazole
derivatives containing amides.
The amide moiety is an important building unit [6-7]
and it is present as a key in many important natural
products and man-made compounds. The practical
application of this method has been limited for a number
of reasons. Ester aminolysis sometimes requires harsh
conditions of high temperature and extended reaction
periods or the use of strong alkali metal catalysts [8-10]
conditions that are not amenable to molecules bearing
sensitive functional groups.
In view of the recent surge in the use of different
catalysts, we wish to report a simple, convenient and
efficient method for the preparation of 2-substitued-N-
arylbenzoxazol-5-carboxamides,
utilizing
cobalt
dipyridine dichloride [12] as catalyst. This method not
only affords the products in excellent yields but also
avoids the problems associated with catalyst cost,
handling, safety and pollution. This catalyst is used for a
variety of organic transformations, which is non-volatile,
non-explosive, easy to handle, and thermally robust.
Enhanced reaction rates and improved selectivity was
obtained in the presence of this catalyst. We wish to
In recent years, several synthetic procedures for direct
conversion of esters to amides is normally conducted
under stringent conditions employing reagents [11] such
as sodium methoxide, lithium aluminum hydride, sodium

1188
M. Sarangapani, D. Sridhar, M. Arjun, M. A. Chari
Vol 45
The 2-substituted-N-aryl-benzoxazole-5-carboxamides
5 have been prepared by refluxing the mixture of 2-
substitued-5-carbomethoxy benzoxazole 4 and substituted
explore the synthesis of 2-substitued-N-arylbenzoxazole-
5-carboxamides utilizing cobalt dipyridine dichloride as
catalyst (Scheme 1).
O
O
O
O2N
HO
OCH3
H2N
HO
OCH3
OCH3
Al(NO3)3
Na2S2O4
AcOH + Ac2O
HO
3
1
2
RCOOH
R1
O
O
NH
CoPy2Cl2
MeOH
NH2
OCH3
N
N
R
R
O
O
5
4
R1
Reflux
RESULTS AND DISCUSSION
anilines under water bath for 50 - 120 minutes by using
cobalt dipyridine dichloride as a metal catalyst. The
reaction mixture was cooled, poured into crushed ice and
neutralized with dilute HCl. The solid thus obtained was
collected by filtration, washed with water and
recrystallized from methanol to obtain the title
compounds. The structures of compounds 5 are confirmed
by their spectroscopic (IR, 1H NMR and Mass) and
analytical data.
For example, IR spectrum in KBr of the compound 5k
showed absorbance frequencies (cm-1): at 3095 (N-H), 1716
(C=O), 1593 (C=N). 1H-NMR spectrum (DMSO-d6) of the
compounds exhibited proton signals (ꢀ ppm) at: 2.1 (s, 3H,
CH3) 6.8-9.2 (m, 7H, Ar-H),10.8 (s, 1H, N-H) Mass
spectrum showed its molecular ion (M+1)+ at m/z 287.
The treatment of 2-substituted-5-carbomethoxy
benzoxazole with different substituted anilines in the
presence of cobalt dipyridine dichloride causes the
formation of 2-substituted-N-aryl-benzoxazole-5-carbox-
amides up to 90% yield. The crude products were purified
either by recrystallization from n-hexane or by silicagel
column chromatography. All the products were
1
characterized by IR, H NMR (Table I and II) and mass
spectral analysis. The reactions of various substituted
anilines with 2-substituted-5-carbomethoxy benzoxazole
in the presence of cobalt dipyridine dichloride is superior
in terms of yields and reaction rates and the results are
presented in the Table III.
Table I
IR spectral data (KBr) 2-Substituted-N-aryl-benzoxazole-5-carboxamides.
ꢁmax in cm-1
Compound
R
Ar
N-H
C=O
C=N
5a
5b
5c
5d
5e
-H
C6H5
C6H5
C6H5
p-Cl
3402.6
3416.2
3405.4
3422.0
3095.9
1706.1
1706.0
1708.1
1696.0
1715.9
1610.1
1597.2
1603.0
1616.0
1592.6
-CH3
-C2H5
-H
-CH3
p-Cl
Table II
1H NMR spectral data of 2-substituted-N-aryl-benzoxazole-5-carboxamides.
Compound
R
Ar
1H NMR (300 MHz, DMSO-d6) (ꢀ, ppm)
7.0 -10.8(10H Ar-H, including NH).
5a
5b
5d
H
C6H5
C6H5
p-Cl
CH3
H
2.29 (s, 3H, CH3), 7.0-10.1 (9H, Ar-H), 9.91 (s, 1H (NH)
7.0-10.95 (9H including NH)
2.21(s, 3H, CH3), 7.0-10.8 (8H, Ar-H, including NH)
5e
CH3
p-Cl

Jul-Aug 2008
Synthesis of some Novel 2-Substituted-N-Aryl-Benzoxazole-5-Carboxamides
1189
We have carried out cobalt dipyridine dichloride
catalyzed synthesis of amides from esters in an efficient
manner and this report happens to be first of its kind to
achieve the products without any undesired products and
the reaction is very efficient and completed in short
reaction time. Usually, the amide formation from esters is
carried out in presence of strong bases, like t-BuOK. But
we have used cobalt dipyridine dichloride as a simple
metal catalyst to achieve the good result.
Infrared spectral data of some compounds were
presented in the Table I. NMR spectral data of the
compounds were presented in the Table II, The physical,
analytical and elemental analysis data of compounds are
given in Table III.
N-aryl-benzoxazole-5-carboxamides from 2-subst-
ituted-5-carbomethoxy benzoxazole by the treatment
of different substituted anilines promoted by cobalt
dipyridine dichloride as
a
catalyst.
Present
methodology offers very attractive features such as
reduced reaction times, higher yields and economic
viability of the catalyst, when compared with
conventional method as well as with other catalysts,
which will have wide scope in organic synthesis. The
simple procedure makes this method economic,
benign and a waste-free chemical process for the
synthesis
of
2-substituted-N-aryl-benzoxazole-5-
carboxamides of biological importance. The
operational simplicity of the procedure is also
Table – III
Physical data of 2-substituted-N-aryl-benzoxazole-5-carboxamides.
Compd.
5a
R
R1
m.p
(OC)
Yield Mol.
(%) Formula
Time
(min)
Elemental analysis % Found (calcd)
C
H
N
H
H
156
80
C14H10N2O2 55
70.50
(70.58)
4.20
(4.20)
11.71
(11.76)
5b
5c
5d
5e
5f
CH3
C2H5
H
H
161
174
165
170
171
148
155
159
160
164
171
154
160
164
138
142
147
82
83
79
81
83
76
90
81
77
79
76
81
85
80
80
81
77
C15H12N2O2 50
C16H14N2O2 50
C15H12N2O2 75
C16H14N2O2 60
C17H16N2O2 90
C15H12N2O3 80
C16H14N2O3 80
C17H15N2O3 75
C14H9ClN2O2 75
C15H11ClN2O2 80
C16H13ClN2O2 100
71.40
(71.42)
72.12
(72.18)
71.38
(71.42)
72.10
(72.18)
72.81
(72.85)
67.10
(67.16)
68.01
(68.08)
69.05
(69.15)
61.71
(61.76)
62.90
(62.93)
64.00
(64.00)
59.50
(59.60)
60.55
(60.60)
61.78
(61.93)
62.80
(62.92)
64.00
(64.05)
64.95
4.70
(4.76)
5.24
(5.26)
4.70
(4.76)
5.20
(5.26)
5.68
(5.71)
4.42
(4.48)
4.90
(4.96)
5.00
(5.08)
3.29
(3.30)
3.80
(3.84)
4.30
(4.33)
3.15
(3.17)
3.70
(3.70)
3.80
(3.87)
4.00
(4.11)
4.50
(4.62)
5.00
11.07
(11.11)
10.50
(10.52)
11.10
(11.11)
10.48
(10.52)
10.00
(10.00)
10.40
(10.44)
9.90
(9.93)
9.44
(9.49)
10.20
(10.29)
9.73
H
p-CH3
p-CH3
p-CH3
p-OCH3
p-OCH3
p-OCH3
p-Cl
CH3
C2H5
H
5g
5h
5i
CH3
C2H5
H
5j
5k
5l
CH3
C2H5
H
p-Cl
(9.79)
9.30
(9.33)
14.80
p-Cl
5m
5n
5o
5p
5q
5r
p-NO2
p-NO2
p-NO2
NHNH2
NHNH2
NHNH2
C14H9N3O4
90
(14.84)
14.00
(14.14)
13.50
(13.54)
20.90
(20.97)
19.80
(19.92)
18.90
(18.98)
CH3
C2H5
H
C15H11N3O4 90
C16H12N3O4 90
C14H11N4O2 120
C15H13N4O2 120
C16H15N4O2 120
CH3
C2H5
(65.08)
(5.08)
CONCLUSION
attractive. To our knowledge, this is first report of an
efficient general method for the synthesis of
2-substituted-N-aryl-benzoxazol-5-carboxamides by
using a simple metal catalyst.
We have developed a simple, convenient and
effective method for facile synthesis of 2-substituted-

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M. Sarangapani, D. Sridhar, M. Arjun, M. A. Chari
Vol 45
REFERENCE AND NOTES
EXPERIMENTAL
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Acknowledgement. The authors are thankful to the Kakatiya
University authorities for encouragement and providing
facilities.