Pd(OAc)2 catalyzed C-H activation of 1,3,4-oxadiazoles and their direct oxidative coupling with benzothiazoles and aryl boronic acids using Cu(OAc)2 as an oxidant

Article abstract of DOI:10.1016/j.tet.2012.12.080

The first direct oxidative coupling of 1,3,4-oxadiazoles with benzothiazoles has been accomplished using Pd(OAc)₂ as a catalyst and Cu(OAc)₂ as an oxidant. The similar combination of the catalyst and the oxidant has also been applied for direct arylation of 1,3,4-oxadiazoles with aryl boronic acids. Several novel oxadiazole derivatives have been prepared in high yields following both the methods.

Full text of DOI:10.1016/j.tet.2012.12.080

Tetrahedron 69 (2013) 2220e2225
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Pd(OAc)2 catalyzed CeH activation of 1,3,4-oxadiazoles and their
direct oxidative coupling with benzothiazoles and aryl boronic
acids using Cu(OAc)2 as an oxidantq
*
N. Salvanna, Gandolla Chinna Reddy, Biswanath Das
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500007, Andhra Pradesh, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 31 August 2012
Received in revised form 21 November 2012
Accepted 13 December 2012
Available online 9 January 2013
The first direct oxidative coupling of 1,3,4-oxadiazoles with benzothiazoles has been accomplished using
Pd(OAc)2 as a catalyst and Cu(OAc)2 as an oxidant. The similar combination of the catalyst and the ox-
idant has also been applied for direct arylation of 1,3,4-oxadiazoles with aryl boronic acids. Several novel
oxadiazole derivatives have been prepared in high yields following both the methods.
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
CeH activation
1,3,4-Oxadiazole
Benzothiazole
Aryl boronic acid
Pd(OAc)2
Cu(OAc)2
1. Introduction
oxadiazoles with terminal alkynes.7i Ofial et al. reported palla-
dium mediated dehydrogenative cross-coupling of azoles with
Substituted oxadiazoles possess different important biological
activities. They work as ester and amide bioisosters.1 They also act as
anticonvulsants and microbial agents.2 In addition, oxadiazole de-
rivatives have multiphoton absorbing properties.3 Some of these
compounds are utilized in development of organic electronics.4 Due
to such valuable applications1e4 in pharmaceutical and material
sciences the synthesis of oxadiazole derivatives is highly desirable.
The transformation of CeH bond of heteroarenes to CeC bond in
the presence of a metal catalyst is an important method to generate
their derivatives.5 The process is atom economic. The two-fold CeH
bond activation has been utilized for cross-coupling of hetero-
arenes with carbocyclic arenes or other heteroarenes.6 Transition
metal catalyzed direct oxidative CeH activation of two very similar
partners to form unsymmetrical biheteroaryl molecules is of great
interest7 but is quite rare because of their tendency to undergo
homocoupling.8 Recently Fagnou et al. developed Pd(II) catalyzed
oxidative coupling of unpreactivated heteroaryls with unactivated
arenes by two-fold CeH activation.6a,b Xi et al. made oxidative
cross-coupling of xanthines with furans and thiophenes.7h Miura
et al. developed Cu(II) mediated oxidative cross-coupling of 1,3,4-
imidazoles.7j
However to our knowledge, metal mediated cross-coupling of
1,3,4-oxadiazoles with benzothiazoles has not yet been reported.
Here we disclose the Pd-catalyzed first direct oxidative coupling of
these two heteroarenes. The direct arylation of 1,3,4-oxadiazoles
with aryl boronic acids using the similar catalyst has also been
reported here.
2. Results and discussion
In continuation of our work9 on the CeH activation of hetero-
arenes we observed that 1,3,4-oxadiazoles when treated with
benzothiazole using Pd(OAc)2 (as a catalyst) and Cu(OAc)2 (as an
oxidant) in the presence of KF and AgNO3 (as an additive) in dry
DMF at 100 ꢀC, afforded the cross-coupling compounds in 12 h
(Scheme 1). The products were formed in high yields (85e94%).
q
Part 233 in the series, ‘Studies on novel synthetic methodologies’.
* Corresponding author. Tel./fax: þ91 40 27160512; e-mail address: biswanathdas@
Scheme 1. Pd(OAc)2 catalyzed oxidative couplingof 1,3,4-oxadiazoles with benzothiazole.
yahoo.com (B. Das).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.12.080

N. Salvanna et al. / Tetrahedron 69 (2013) 2220e2225
2221
Table 2
Initially, 2-phenyl 1,3,4-oxadiazole (1a) was treated with ben-
Pd(OAc)2 catalyzed CeH activation of 1,3,4-oxadiazoles with benzothiazolea
zothiazole (2) for optimization of the reaction conditions. The re-
action was conducted with variable amounts of Pd(OAc)2 and
different oxidants. As an additive only KF or a combination of KF
and AgNO3 was used (Table 1).
Table 1
Entry
1
1
R
Product 3
Yieldb (%)
Optimization studies of Pd(OAc)2 catalyzed CeH activation of 2-phenyl 1,3,4-
oxadiazole 1(a) with benzothiazole 2a
1a
C6H5
92
91
2
3
1b
1c
4-MeC6H4
4-ClC6H4
Entry
Pd(OAc)2
(mol %)
Oxidant (equiv)
Additive (equiv)
Yieldb (%)
1
2
3
4
5
6
7
8
5
5
5
10
10
10
10
10
5
Cu(OAc)2 (1.0)
d
d
Trace
d
KF (3.0)þAgNO3 (1.5)
85
Cu(OAc)2 (1.0)
Cu(OAc)2 (1.0)
TEMPO (1.0)
TBHP (1.0)
Benzoquinone
Cu(OAc)2 (2.0)
Cu(OAc)2 (2.0)
Cu(OAc)2 (2.0)
Cu(OAc)2 (10)
Cu(OAc)2 (2.0)
KF (1.0)
<10
46
20
21
20
KF (3.0)þAgNO3 (1.5)
KF (3.0)þAgNO3 (1.5)
KF (3.0)þAgNO3 (1.5)
KF (3.0)þAgNO3 (1.5)
KF (3.0)þAgNO3 (1.5)
KF (3.0)DAgNO3 (1.5)
KF (3.0)þAgNO3 (1.5)
KF (3.0)þAgNO3 (1.5)
KF (3.0)þAgNO3 (1.5)
4
5
1d
1e
4-OMeC6H4
4-CF3C6H4
94
88
92
9
92
10
11
12
5
5
92c,d
42
d
de
Bold entry signifies optimized reaction condition.
a
Reaction conditions: 2-phenyl 1,3,4-oxadiazole 1a (1.0 mmol), benzothiazole 2
(1.3 mmol), Pd(OAc)2 (mol %), oxidant (equiv), additive (equiv), at 100 ꢀC, over 12 h
in dry DMF.
6
7
1f
2-Furyl
91
89
b
Isolated yield of 3a after column chromatography.
c
Reaction was carried out at 160 ꢀC.
d
At room temperature no product could be formed.
e
1g
3-Nicotinyl
Almost quantitative recovery of starting materials.
The present conversion was found to be most effective when
Pd(OAc)2 (5 mol %) and Cu(OAc)2 (2.0 equiv) along with the addi-
tive, KF (3.0 equiv) and AgNO3 (1.5 equiv) were used in dry DMF at
100 ꢀC (Table 1, entry 9). The yield was 92% after 12 h. When the
reaction was conducted at higher temperature (160 ꢀC) the yield
was not increased (Table 1, entry 10). But at room temperature no
product could be detected within 12 h. The yield was not affected if
the amount of Pd(OAc)2 was increased to 10 mol % (Table 1, entry 8).
However, in the absence of Cu(OAc)2 the present conversion did not
proceed and in the absence of the additive only a trace amount of
the product was formed (Table 1, entry 1 and 2). Even with only KF
the yield was poor (>10%) (Table 1, entry 3). Instead of Cu(OAc)2
some other oxidizing agents, such as TBHP, TEMPO, and benzo-
quinone were also used but the yields were low (w20%) (Table 1,
entry 5e7). However, only with Cu(OAc)2 [without using Pd(OAc)2]
the conversion did not take place at all (Table 1, entry 12). The re-
action was also attempted in toluene as solvent but yield was low.
The above standardization method was followed for cross-
coupling of various 1,3,4-oxadiazoles with benzothiazole to prepare
a series of oxadiazole derivatives (Table 2). Both the arene and
heteroarene moieties were attached with the starting oxadiazoles.
The products were formed in high yields (85e94%) in 12 h. No any
side product could be isolated. Structures of the prepared oxadia-
zoles were settled from their spectral (IR, 1H and 13C NMR, and
ESIMS) and analytical data.
a
Reaction conditions: 2-aryl 1,3,4-oxadiazole 1 (1.0 mmol), benzothiazole 2
(1.3 mmol), Pd(OAc)2 (5 mol %), Cu(OAc)2 (2 equiv), KF (3.0 equiv), AgNO3 (1.5 equiv)
at 100 ꢀC, over 12 h in dry DMF.
b
Isolated yield of 3 after column chromatography.
oxidized by Cu(II)/Ag(I) to regenerate Pd(II) to complete the cata-
lytic cycle. The presence of Ag(I) may also be facilitate the cleavage
of CeH bond of the heteroarenes to form complex A.7j
On the basis of understanding of metal catalyzed cross-coupling
reactions,5e10 a plausible mechanism of present conversion is
shown in Scheme 2. The reaction possibly proceeds through double
CeH bond cleavage of two heteroarenes followed by the CeC bond
coupling strategy. The mixed hetero arylePd complex A is the key
intermediate, which underwent reductive elimination to form the
product 3. Pd0 species generated by this sequence was possibly
Scheme 2. Plausible mechanism of CeH activation of 1,3,4-oxadiazoles with
benzothiazoles.
We have not got any homocoupling product. The reaction was
spectroscopically (1H NMR) monitored during an interval of 3 h.
Only the cross-coupling product was detected. The yield was
increased with time and the highest yield was observed in 12 h.

2222
N. Salvanna et al. / Tetrahedron 69 (2013) 2220e2225
Table 4
The combination of Pd(OAc)2 and Cu(OAc)2 has also been
Pd(OAc)2 catalyzed oxidative coupling of 1,3,4-oxadiazoles with aryl boronic acida,b
employed for direct arylation of 1,3,4-oxadiazole by treatment with
aryl boronic acid (Scheme 3). 2,20-Bipyridine was used as a ligand
and K3PO4 as a base. The reaction was conducted in DMSO at 100 ꢀC
under aerobic conditions. The products were formed in high yields
(83e92%) in 12 h.
___________________________________________________
Scheme 3.
___________________________________________________
The direct arylation of heteroarenes through metal catalyzed
CeH bond functionalization is an important method for the prep-
aration of aryl substituted heteroarenes.11 Miura et al. developed
Ni-catalyzed CeH activation of azoles with aryl boronic acids.11c
You et al. reported the same reaction using PdeCu bimetallic sys-
tem as a catalyst.11i Here we have utilized our developed system
(catalyst, oxidant, ligand, and base) used above for the coupling of
oxadiazoles with benzothiazoles.
Initially for standardization of the conversion 2-phenyl 1,3,4-
oxadiazole (1a) was treated with 4-ethyl phenyl boronic acid (4a)
under different conditions. The amount of Pd(OAc)2 was variable
and different oxidants, bases, and ligands were used (Table 3). The
present conversion was observed to undergo most efficiently when
Pd(OAc)2 (5 mol %) and Cu(OAc)2 (10 mol %) were employed using
K3PO4 (base) and 2,20-bipyridine (ligand) in DMSO at 100 ꢀC under
air. The yield was maximum (89%) in 12 h. At room temperature the
reaction did not proceed. In absence of Pd(OAc)2 and Cu(OAc)2 or
either of them the reaction was also not successful, K3PO4 and
Cs2CO3 decreased the yields of the products and under the ligand-
free conditions the yield were very low. In an inert atmosphere (N2)
only a trace amount of product was formed.
N
N
N
N
C2H5
O
O
5ab (91)
5aa (89)
N
N
N
N
O
O
S
Cl
Cl
5ac
(87)
N
5cb
(86)
N
Cl
N
N
O
O
Me
F
Cl
5ce
5cf (86)
(83)
N
N
N
N
N
O
O
N
F3C
5eh (92)
F3C
5eg (89)
N
N
Cl
N
N
O
F
O
O
Cl
O
5fe
(90)
Table 3
5fi (87)
_______________________________________________________________________________________________________
Optimization studies of Pd(OAc)2 catalyzed CeH activation of 2-phenyl 1,3,4-
aReaction conditions: 2-aryl 1, 3, 4-oxadiazole 1 (1.0 mmol), aryl boronic acid 4
(1.3 mmol), Pd(OAc)2 (5 mol%), Cu(OAc)2 (10 mol%), K3PO4 (1.5 equiv), 2, 2'-
bipy (30 mol%) over 12 h in DMSO under air. bIn parenthesis, isolated yield of 5
after column chromatography.
oxadiazoles with 4-ethyl phenyl boronic acida
boronic acids (Table 4). The oxadiazoles as well as boronic acids
contained both aryl and heteroaryl moieties. Boronic acids having
halogen (X¼Cl, F) underwent the conversion smoothly, but the re-
action did not proceed with the boronic acids containing eCN
or eCOOR group. In absence of Pd(OAc)2 no reaction took place
(Table 3, entry 12). Following the present method several known and
unknown oxadiazole derivatives were prepared. The structures of
the compounds were established from the spectral (IR, 1H and 13C
NMR, and ESIMS) and analytical data.
With an understanding of the metal-catalyzed direct arylation of
heteroarenes11 a plausible mechanism of the above conversion is
presented in Scheme 4. The initial interaction of divalent palladium
(in assistance with the ligand) with boronic in the presence of the
base produced the aryl palladium complex, which reacted with the
oxadiazole to afford the key intermediate A0. The reductive elimi-
nation of A0 yielded the arylated product 5. The resulting Pd0 was
oxidized to PdII in the presenceof CuII forcomplete the catalytic cycle.
Entry
Oxidant
(10 mol %)
Base
(1.5 equiv)
Ligand
(30 mol %)
Yieldb
(%)
1
2
3
4
5
6
7
8
d
K3PO4
K3PO4
K3PO4
K3PO4
Cs2CO3
K3PO4
Cs2CO3
K3PO4
Cs2CO3
K3PO4
Na2CO3
K3PO4
d
<5
10
40
68
78
72
35
89
42
84
49
N.Rc
Cu(OAc)2
TEMPO
TBHP
Cu(OAc)2
Cu(OAc)2
TEMPO
Cu(OAc)2
TBHP
d
DMEDA
Phen
Bipy
DMEDA
Bipy
Bipy
Bipy
Phen
Bipy
Bipy
9
10
11
12
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Bold entry signifies optimized reaction condition.
a
Reaction conditions: 2-phenyl 1,3,4-oxadiazole 1a (1.0 mmol), 4-ethyl phenyl
boronic acid 4a (1.3 mmol), Pd(OAc)2 (5 mol %), oxidant (10 mol %), base (1.5 equiv),
ligand (30 mol %) over 12 h in DMSO under air.
b
Isolated yield of 5aa after column chromatography.
Absence of Pd(OAc)2, no reaction took place.
c
3. Conclusions
Following the standardization of the above reaction, direct ary-
lation of different 1,3,4-oxadiazoles was carried out using various
In conclusion, we have developed an efficient method for CeH
activation of 1,3,4-oxadiazoles using Pd(OAc)2 as a catalyst and

N. Salvanna et al. / Tetrahedron 69 (2013) 2220e2225
2223
10 min at room temperature then heated at 100 ꢀC for 12 h. The
progress of the reaction was monitored by TLC. After consumption
of starting material the reaction mixture was allowed to cool and
subsequently extracted with EtOAc. The combined organic extracts
were dried over anhydrous Na2SO4. Concentration in vacuo fol-
lowed by column chromatography (EtOAc/hexane: 5:95 to 10:90)
gave pure compound 5 in 83e92% yield.
4.4. Spectral data of all compounds are given below
4.4.1. 2-(Benzo[d]thiazol-2-yl)-5-phenyl-1,3,4-oxadiazole (3a) (Table 2,
entry 1). Light yellow solid, mp: 159e161 ꢀC, Rf 0.37 (20% EtOAc/
hexane); IR (KBr): 2272, 1626, 1540, 1464, 1309 cmꢁ1 1H NMR
;
Scheme 4.
(200 MHz, CDCl3):
d 8.32e8.24 (2H, m, AreH), 8.12 (1H, m, AreH),
7.99 (1H, dd, J 8.0, 2.0 Hz, AreH), 7.66e7.49 (5H, m, AreH); 13C NMR
(50 MHz, CDCl3): d 165.9, 160.2, 153.6, 151.0, 135.4, 132.2, 129.1, 127.9,
Cu(OAc)2 as an oxidant. The method has been applied for direct
coupling of these heteroarenes with benzothiazole and aryl boronic
acids to prepare their derivatives. The Pd(OAc)2 catalyzed cross-
coupling of oxadiazoles and benzothiazole has been reported here
for the first time.
127.8, 127.7, 124.3, 123.2, 122.0; ESIMS: m/z 280 [MþH]þ; Anal. Calcd
for C15H9N3OS: C, 64.50; H, 3.25; N,15.04. Found: C, 64.52; H, 3.22; N,
15.07.
4.4.2. 2-(Benzo[d]thiazol-2-yl)-5-(p-tolyl)-1,3,4-oxadiazole(3b)(Table 2,
entry 2). Light yellow solid, mp: 148e150 ꢀC, Rf 0.35 (20% EtOAc/
4. Experimental section
4.1. General
hexane); IR (KBr): 2380, 1618, 1539, 1491, 1316 cmꢁ1 1H NMR
;
(200 MHz, CDCl3):
d 8.27 (1H, dd, J 8.0, 2.0 Hz, AreH), 8.12 (2H d, J
8.0 Hz, AreH), 8.02 (1H, dd, J 8.0, 2.0 Hz, AreH), 7.63e7.52 (2H, m,
AreH), 7.38 (2H, d, J 8.0 Hz, AreH), 2.42 (3H, s, eCH3); 13C NMR
Melting points were measured on a Buchi 510 apparatus and are
uncorrected. The spectra were recorded with the following in-
struments; IR: PerkineElmer RX FT-IR spectrophotometer; ESIMS:
VG-Autospec micromass spectrometer. 1H NMR and 13C NMR
spectra were recorded on a 200 MHz and 50 MHz spectrometers
(50 MHz, CDCl3):
d 166.1, 160.0, 153.3, 150.9, 143.2, 135.2, 130.0,
127.2, 127.0, 126.8, 124.5, 122.0, 21.9; ESIMS: m/z 294 [MþH]þ; Anal.
Calcd for C16H11N3OS: C, 65.51; H, 3.78; N, 14.32. Found: C, 65.48; H,
3.82; N, 14.36.
using the solvent peak as internal reference (CDCl3,
77.0). Data are reported in the following order: chemical shift (
d
H: 7.26;
d
C:
4.4.3. 2-(Benzo[d]thiazol-2-yl)-5-(4-chlorophenyl)-1,3,4-oxadiazole
(3c) (Table 2, entry 3). White viscous liquid, Rf 0.35 (20% EtOAc/
hexane); IR (KBr): 2382, 1693, 1537, 1309 cmꢁ1; 1H NMR (200 MHz,
d) in
parts per million; multiplicities are indicated s¼singlet, d¼doublet,
t¼triplet, q¼quartet, m¼multiplet; coupling constants (J) are in
hertz. All reactions were monitored by thin-layer chromatography
(TLC) using silica gel F254 pre-coated plates. Visualization was ac-
complished with UV-light or I2 stain. Organic reactions were dried
over anhydrous Na2SO4. Solvents for the catalytic reactions were
technical grade. Solvents for chromatography (EtOAc, hexane) were
technical grade and distilled prior to use.
CDCl3):
d
8.22e8.11 (2H, m, AreH), 7.94 (1H, dd, J 8.0, 2.0 Hz, AreH),
165.1, 160.2,
7.61e7.42 (5H, m, AreH); 13C NMR (50 MHz, CDCl3):
d
153.5, 150.8, 139.2, 135.8, 129.9, 129.0, 127.5, 127.4, 125.0, 122.1;
ESIMS: m/z 314, 316 [MþH]þ; Anal. Calcd for C15H8ClN3OS: C, 57.42;
H, 2.57; N, 13.39. Found: C, 57.46; H, 2.54; N, 13.41.
4.4.4. 2-(Benzo[d]thiazol-2-yl)-5-(4-methoxyphenyl)-1,3,4-
oxadiazole (3d) (Table 2, entry 4). White solid, mp: 144e146 ꢀC, Rf
0.41 (30% EtOAc/hexane); IR (KBr): 2385, 1609, 1492, 1428,
4.2. General procedure for oxidative cross-coupling of 2-aryl
1,3,4-oxadiazole with benzothiazole
1257 cmꢁ1; 1H NMR (200 MHz, CDCl3):
d 8.25 (1H, dd, J 8.0, 2.0 Hz,
AreH), 8.20 (2H, d, J 8.0 Hz, AreH), 8.02 (1H, dd, J 8.0, 2.0 Hz, AreH),
7.68e7.52 (2H, m, AreH), 7.04 (2H, d, J 8.0 Hz, AreH), 3.92 (3H, s,
In a 10 mL round bottom flask Pd(OAc)2 (5 mol %, 11.3 mg),
Cu(OAc)2 (2 equiv, 404 mg), KF (3.0 equiv, 174 mg), AgNO3
(1.5 equiv, 255 mg), 2-aryl 1,3,4-oxadiazole (1 mmol), and benzo-
thiazole (1.3 mmol) were taken in dry DMF (2.5 mL). The reaction
mixture was stirred for 10 min at room temperature then heated at
100 ꢀC for 12 h. The progress of the reaction was monitored by TLC.
After consumption of starting material the reaction mixture
was allowed to cool and subsequently extracted with EtOAc. The
combined organic extracts were dried over anhydrous Na2SO4.
Concentration in vacuo followed by column chromatography
(EtOAc/hexane: 5:95 to 10:90) gave pure compound 3 in 85e94%
yield.
eOCH3); 13C NMR (50 MHz, CDCl3):
d 166.1, 163.0, 159.9, 153.8,
151.2, 135.5, 129.6, 127.1, 127.0, 124.9, 122.1, 114.6, 55.8; ESIMS: m/z
310 [MþH]þ; Anal. Calcd for C16H11N3O2S: C, 62.12; H, 3.58; N,
13.58. Found: C, 62.09; H, 3.61; N, 13.55.
4.4.5. 2-(Benzo[d]thiazol-2-yl)-5-(4-(trifluoromethyl)phenyl)-1,3,4-
oxadiazole (3e) (Table 2, entry 5). Pink solid, mp: 147e149 ꢀC, Rf 0.51
(30% EtOAc/hexane); IR (KBr): 2417, 1553, 1462, 1627, 1126 cmꢁ1; 1H
NMR (200 MHz, CDCl3):
8.0 Hz, AreH), 8.00 (1H, d. J 8.0 Hz, AreH), 7.82 (2H, d, J 8.0 Hz, AreH),
7.63e7.50 (2H, m, AreH); 13C NMR (50 MHz, CDCl3):
165.0, 160.9,
d 8.39 (2H, d, J 8.0 Hz, AreH), 8.22 (1H, d, J
d
153.4,150.5,136.0,133.8,127.9,127.5,127.4,126.7 (q, J 30.0 Hz),126.4,
125.1, 122.0; ESIMS: m/z 348 [MþH]þ; Anal. Calcd for C16H8F3N3OS:
C, 55.33; H, 2.32; N, 12.10. Found: C, 55.35; H, 2.34; N, 12.07.
4.3. General procedure for oxidative coupling of 1,3,4-
oxadiazoles with aryl boronic acid
In a 10 mL round bottom flask Pd(OAc)2 (5 mol %, 11 mg),
Cu(OAc)2 (10 mol %, 20 mg), 2,20-bipyridine (30 mol %, 44 mg) and
K3PO4 (1.5 mmol, 318.3 mg), aryl boronic acid (1.3 mmol), and 2-
aryl 1,3,4-oxadiazole (1.0 mmol)were added to a solution of
DMSO (2.5 mL) under air. The reaction mixture was stirred for
4.4.6. 2-(Benzo[d]thiazol-2-yl)-5-(furan-2-yl)-1,3,4-oxadiazole (3f)
(Table 2, entry 6). Dark solid, mp: 153e155 ꢀC, Rf 0.35 (20% EtOAc/
hexane); IR (KBr): 2414, 1623, 1518, 1451, 1312 cmꢁ1 1H NMR
;
(200 MHz, CDCl3):
d 8.20 (1H, dd, J 8.0, 2.0 Hz, AreH), 7.99 (1H, dd, J
8.0, 2.0 Hz, AreH), 7.72 (1H, m, AreH), 7.60e7.48 (2H, m, AreH), 7.37

2224
N. Salvanna et al. / Tetrahedron 69 (2013) 2220e2225
(1H, m, AreH), 6.68 (1H, m, AreH); 13C NMR (50 MHz, CDCl3):
(20% EtOAc/hexane); IR (KBr): 2384, 1604, 1465, 1253 cmꢁ1
NMR (200 MHz, CDCl3): 8.11e8.00 (3H, m, AreH), 7.50 (2H, d, J
8.0 Hz, AreH), 7.12e7.03 (2H, m, AreH), 2.43 (3H, s, eCH3); 13C
;
1H
d
159.5,158.7,153.2,150.1,146.7,145.8,135.2,127.9,127.8,124.5,122.0,
d
115.9, 112.2; ESIMS: m/z 270 [MþH]þ; Anal. Calcd for C13H7N3O2S: C,
57.98; H, 2.62; N, 15.60. Found: C, 58.01; H, 2.59; N, 15.62.
NMR (50 MHz CDCl3): d 164.0, 145.2, 145.1, 144.0, 138.1, 129.5, 128.4,
125.8, 122.3, 118.2, 118.1, 21.2; ESIMS: m/z 305, 307, 309 [MþH]þ;
Anal. Calcd for C15H10Cl2N2O: C, 59.04; H, 3.30; N, 9.18. Found: C,
59.06; H, 3.27; N, 9.21.
4.4.7. 2-(Benzo[d]thiazol-2-yl)-5-(pyridin-3-yl)-1,3,4-oxadiazole
(3g) (Table 2, entry 7). Light yellow solid, mp: 157e159 ꢀC, Rf 0.51
(40% EtOAc/hexane); IR (KBr): 2407, 1596, 1536, 1458, 1314 cmꢁ1
;
1H NMR (200 MHz, CDCl3):
d
9.45 (1H, d, J 2.0 Hz, AreH), 8.82 (1H,
4.4.14. 2-(Pyridin-3-yl)-5-(4-(trifluoromethyl)phenyl)-1,3,4-
oxadiazole (5eg) (Table 4). Brown solid, mp: 165e167 ꢀC, Rf 0.45
m, AreH), 8.54 (1H, dd, J 8.0, 2.0 Hz, AreH), 8.28 (1H, dd, J 8.0,
2.0 Hz, AreH), 8.02 (1H, dd, J 8.0, 2.0 Hz, AreH), 7.66e7.50 (3H, m,
(50% EtOAc/hexane); IR (KBr): 2405, 1605, 1547, 1492, 1323 cmꢁ1
;
AreH); 13C NMR (50 MHz, CDCl3):
d
163.8, 160.6, 153.3, 153.1, 152.2,
1H NMR (200 MHz, CDCl3):
d 9.41 (1H, d, J 2.0 Hz, AreH), 8.84 (1H,
148.2,135.5, 134.9, 127.9, 127.8, 125.0, 124.0,121.8, 119.8; ESIMS: m/z
303 [MþNa]þ; Anal. Calcd for C14H8N4OS: C, 59.99; H, 2.88; N,
19.99. Found: C, 60.01; H, 2.86; N, 20.02.
dd, J 7.0, 2.0 Hz, AreH), 8.45 (1H, dt, J 8.0, 2.0 Hz, AreH), 8.31 (2H, d,
J 8.0 Hz, AreH), 7.84 (2H, d, J 8.0 Hz, AreH), 7.52 (1H, dd, J 8.0,
7.0 Hz, AreH); 13C NMR (50 MHz, CDCl3):
d 164.2, 163.5, 152.9,
148.2, 134.9, 133.5, 128.0, 127.3, 126.9, 124.0, 122.1 (q, J 227 Hz),
120.2; ESIMS: m/z 292 [MþH]þ; Anal. Calcd for C14H8F3N3O: C,
57.74; H, 2.77; N, 14.43. Found: C, 57.71; H, 2.75; N, 14.47.
4.4.8. 2-(4-Ethylphenyl)-5-phenyl-1,3,4-oxadiazole (5aa) (Table 4).
White solid, mp: 114e116 ꢀC, Rf 0.42 (20% EtOAc/hexane); IR (KBr):
2397, 1612, 1548, 1488, 1269 cmꢁ1 1H NMR (200 MHz, CDCl3):
;
d
8.17e8.10 (2H, m, AreH), 8.02 (2H, d, J 8.0 Hz, AreH), 7.58e7.50
4.4.15. 2-(Pyridin-4-yl)-5-(4-(trifluoromethyl)phenyl)-1,3,4-
oxadiazole (5eh) (Table 4). Brown solid, mp: 168e170 ꢀC, Rf 0.45 (50%
(3H, m, AreH), 7.32 (2H, d, J 8.0 Hz, AreH), 2.72 (2H, q, J 7.0 Hz,
eCH2e), 1.28 (3H, t, J 7.0 Hz, eCH3); 13C NMR (50 MHz, CDCl3):
EtOAc/hexane); IR (KBr): 2394, 1614, 1498, 1242 cmꢁ1 1H NMR
;
d
164.8,164.5,148.8,131.8,129.1,128.8,127.2,127.1,124.1,121.2, 29.0,
(200 MHz, CDCl3):
d 8.88 (2H, d, J 7.0 Hz, AreH), 8.30 (2H, d, J 8.0 Hz,
15.2; ESIMS: m/z 251 [MþH]þ; Anal. Calcd for C16H14N2O: C, 76.78;
AreH), 7.99 (2H, d, J 7.0 Hz, AreH), 7.82 (2H, d, J 8.0 Hz, AreH); 13C NMR
H, 5.64; N, 11.19. Found: C, 76.76; H, 5.68; N, 11.16.
(50 MHz, CDCl3): d 164.2, 163.5, 151.1, 144.3, 131.0, 127.9, 126.3, 126.1,
124.0 (q, J 227 Hz), 120.6; ESIMS: m/z 292 [MþH]þ; Anal. Calcd for
4.4.9. 2-(Naphthalen-1-yl)-5-phenyl-1,3,4-oxadiazole (5ab) (Table 4).
Brown solid, mp: 113e115 ꢀC, Rf 0.40 (20% EtOAc/hexane); IR (KBr):
C14H8F3N3O: C, 57.74; H, 2.77; N,14.43. Found: C, 57.76; H, 2.73; N,14.41.
2395,1605,1547,1449,1267 cmꢁ1; 1H NMR (200 MHz, CDCl3):
d
8.49
4.4.16. 2-(2,4-Dichlorophenyl)-5-(furan-2-yl)-1,3,4-oxadiazole (5fi)
(Table 4). Brown solid, mp: 183e185 ꢀC, Rf 0.40 (20% EtOAc/hex-
(1H, m, AreH), 8.22e8.16 (3H m, AreH), 7.93 (2H, d, J 8.0 Hz, AreH),
7.84 (1H, m, AreH), 7.59e7.50 (5H, m, AreH); 13C NMR (50 MHz,
ane); IR (KBr): 2408, 1631, 1453, 1279 cmꢁ1 1H NMR (200 MHz,
;
CDCl3):
d
165.0, 134.9, 133.1, 131.8, 129.1, 129.0, 128.0, 127.9, 127.3,
CDCl3):
7.69 (1H, d, J 2.0 Hz, AreH), 7.62 (1H, d, J 8.0 Hz, AreH), 7.28 (1H, m,
AreH), 6.64 (1H, m, AreH); 13C NMR (50 MHz, CDCl3):
162.3,
158.1, 146.5, 139.5, 136.4, 133.9, 131.5, 128.8, 126.2, 123.3, 115.0,
112.8; ESIMS: m/z 281[MþH]þ; Anal. Calcd for C12H6Cl2N2O2: C,
51.27; H, 2.15; N, 9.97. Found: C, 51.24; H, 2.17; N, 9.94.
d 8.21 (1H, m, AreH), 7.99 (1H, dd, J 8.0 Hz, 2.0 Hz, AreH),
127.2, 127.1, 124.2, 123.4, 121.1; ESIMS: m/z 273 [MþH]þ; Anal. Calcd
for C18H12N2O: C, 79.39; H, 4.44; N,10.29. Found: C, 79.42; H, 4.41; N,
10.32.
d
4.4.10. 2-Phenyl-5-(thiophen-3-yl)-1,3,4-oxadiazole (5ac) (Table 4).
Light yellow solid, mp: 117e119 ꢀC, Rf 0.45 (20% EtOAc/hexane); IR
(KBr): 2402, 1590, 1481, 1448, 1261 cmꢁ1; 1H NMR (200 MHz, CDCl3):
4.4.17. 2-(4-Fluorophenyl)-5-(furan-2-yl)-1,3,4-oxadiazole
(Table 4). Brown solid, mp: 130e132 ꢀC, Rf 0.40 (20% EtOAc/hexane);
IR (KBr): 2412, 1632, 1605, 1497, 1233 cmꢁ1 1H NMR (200 MHz,
CDCl3): 8.20e8.08 (2H, m, AreH), 7.62 (1H, m, AreH), 7.28e7.15 (3H,
m, AreH), 6.61 (1H, m, AreH); 13C NMR (50 MHz, CDCl3):
165.0 (d,
(5fe)
d
8.13e8.07 (3H, m, AreH), 7.72 (1H, m, AreH), 7.55e7.42 (4H, m,
AreH); 13C NMR (50 MHz, CDCl3):
d
163.9, 161.3, 131.8, 129.1, 127.5,
;
126.9, 126.1, 125.3, 123.9; ESIMS: m/z 229 [MþH]þ; Anal. Calcd for
d
C12H8N2OS:C, 63.14;H, 3.53;N,12.27. Found:C,63.12;H, 3.57;N,12.24.
d
J¼280 Hz),157.7,145.9,129.4(d, J 5.0 Hz),126.8,120.1,116 (d, J 30.0Hz),
115.2, 112.3; ESIMS: m/z 231 [MþH]þ; Anal. Calcd for C12H7FN2O2: C,
62.61; H, 3.07; N, 12.17. Found: C, 62.63; H, 3.04; N, 12.14.
4.4.11. 2-(4-Chlorophenyl)-5-(naphthalen-1-yl)-1,3,4-oxadiazole
(5cb) (Table 4). White solid, mp: 163e165 ꢀC, Rf 0.38 (20% EtOAc/
hexane); IR (KBr): 2412, 1603, 1474, 1270 cmꢁ1; 1H NMR (200 MHz,
CDCl3):
8.0 Hz, AreH), 7.94 (2H, d, J 8.0 Hz, AreH), 7.85 (1H, d, J 8.0 Hz, AreH),
7.59e7.50 (4H, m, AreH); 13C NMR (50 MHz, CDCl3):
165.0, 163.9,
138.1, 134.5, 132.7, 129.4, 128.9, 128.7, 128.1, 127.9, 127.8, 127.3, 127.1,
123.0, 122.5, 120.8; ESIMS: m/z 307, 309 [MþH]þ; Anal. Calcd for
C18H11ClN2O:C,70.48;H, 3.61;N,9.13.Found:C,70.43;H, 3.64;N,9.17.
d 8.58 (1H, m, AreH), 8.19 (1H, d, J 8.0 Hz, AreH), 8.11 (2H, d, J
Acknowledgements
d
The authors thank CSIR and UGC, New Delhi for financial
assistance.
Supplementary data
4.4.12. 2-(4-Chlorophenyl)-5-(4-fluorophenyl)-1,3,4-oxadiazole
(5ce) (Table 4). White solid, mp: 207e209 ꢀC, Rf 0.37 (20% EtOAc/
hexane); IR (KBr): 2408, 1606, 1489, 1229 cmꢁ1; 1H NMR (200 MHz,
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2012.12.080.
CDCl3):
(2H, d, J 8.0 Hz, AreH), 7.21 (2H, t, J 8.0 Hz, AreH); 13C NMR
(50 MHz, CDCl3): 166.4 (d, J 280.0 Hz), 164.0, 137.2, 129.6, 129.2 (d,
d 8.18e8.10 (2H, m, AreH), 8.04 (2H, d, J 8.0 Hz, AreH), 7.51
References and notes
d
J 100 Hz), 128.4, 122.8, 120.2, 116.9 (d, J 25.0 Hz); ESIMS: m/z 275,
277 [MþH]þ; Anal. Calcd for C14H8ClFN2O: C, 61.22; H, 2.94; N,
10.20. Found: C, 61.24; H, 2.93; N, 10.18.
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