Synthesis of new functionalized 2-alkylsulfanyl-5-(1h-indol-2-yl)-1,3,4- oxadiazole and a facile thio-aza-claisen rearrangement of the s-allyl analog

Article abstract of DOI:10.2174/157017809789124902

The S-alkylated indolyloxadiazoles 2a-l were obtained regioselectively by alkylation of 5-(1 H-indol-2-yl)- 1,3,4-oxadiazole-2(3H)-thione 1, using TEA as acid scavenger. Alkylation of 1 with 1-bromopropane, 1-bromobutane, 1-bromoundecan, in the presence o

Full text of DOI:10.2174/157017809789124902

462
Letters in Organic Chemistry, 2009, 6, 462-469
Synthesis of New Functionalized 2-Alkylsulfanyl-5-(1H-indol-2-yl)-1,3,4-
Oxadiazole and a Facile Thio-Aza-Claisen Rearrangement of the S-Allyl
Analog
El Sayed H. El Ashry*,a,b, El Sayed H. El Tamanyc, Mohy El Din Abd El Fattahc, Mohamed R.E.
Alyd and Ahmed T.A. Boraeia
aInternational Center for Chemical and Biological Sciences, H.E.J. Research Institute of Chemistry, Karachi University,
Karachi 75270, Pakistan
bOn leave from Chemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt
cChemistry Department, Faculty of Science, Suez Canal University, Ismailia, Egypt
dChemistry Department, Faculty of Applied Science, Suez Canal University, Port Said, Egypt
Received March 18, 2009: Revised May 05, 2009: Accepted May 05, 2009
Abstract: The S-alkylated indolyloxadiazoles 2a-l were obtained regioselectively by alkylation of 5-(1H-indol-2-yl)-
1,3,4-oxadiazole-2(3H)-thione 1, using TEA as acid scavenger. Alkylation of 1 with 1-bromopropane, 1-bromobutane, 1-
bromoundecan, in the presence of K2CO3, yielded the N-alkylated products 3i-j,m in addition to the S-alkylated analogs
2i-j,m.
A facile thio-aza-Claisen rearrangement (SꢀN allylic rearrangement) of the S-allyl-oxadiazole 2k to the N-allyl analog
3k was achieved in excellent yield. Further allylation of 2k and 3k in the presence of K2CO3 led to allylation of the NH
indole ring producing 5 and 6, respectively. Benzylation of 1 in the presence of K2CO3 yielded 7 which resisted the SꢀN
1
migration of the benzyl group. The H NMR, 13C NMR and mass spectra confirmed the structures and differentiated
between the N- and S-alkylated products.
Keywords: Indoles, oxadiazoles, indolyloxadiazoles, thio-aza-Claisen rearrangement, allylic rearrangement.
INTRODUCTION
thermal rearrangement of the cinnamylthiothiazole, in a
sealed tube (>265 C) for several hours, led to charring [12].
o
During our recent studies of the chemistry of
thioglycosides [1-3], and nucleoside analogs [4], indolyl-
oxadiazolethione was incorporated as the aglycon part via
an alkylation process. The regioselectivity of the alkylation
of 5-(1H-indol-2-yl)-1,3,4-oxadiazole-2(3H)-thione 1 was
studied using alkyl halides having different functionalities
which could give the S- and/or N-alkyl derivatives. When
the alkyl group is allyl moiety, its rearrangement from sulfur
to nitrogen can be a facile method for preparing the
respective N-allyl derivative. Limited reports [5-8] dealing
with this phenomenon, have generally suggested that N=C-
S-C-C=C gives S=C-N-C-C=C on heterocyclic systems.
With azobisisobutyronitrile (AIBN) as a radical initiator in
refluxing bromobenzene (165 C) 2-allylthiothiazole gave
o
the N-allyl and the starting S-allyl in the ratio of 2:3 [13]. It
is not clear, whether that rearrangement is a regular [3,3]-
sigmatropic change or a non thio-Claisen type migration of
the allyl moiety via a free radical mechanism [14]. The PdII-
salt PdCl2(PhCN)2 was found to catalyze the allylic
rearrangement of S-allylpyrimidine and S-allyltriazine
yielding the rearranged product in a high yield [15,16]. The
available synthetic methods gave low yields and were time
consuming. No such rearrangement has been reported so far
in the oxadiazole series. In the present work we describe an
efficient high yielding method, for synthesis of the N-allyl-
oxadiazole from the S-allylsulfanyl-oxadiazole.
Allylthio-benzimidazoles
[6],
benzothiazolines
[7],
imidazolines [9], and 1,2,4-triazin-5(4H)-ones [5,7] have
been reported to undergo thermal SꢀN allylic
rearrangement, but 5-(allylthio)pyrimidines [10], and 8-
(allylthio)caffeines [11] did not rearrange. Heating at high
temperatures in a nucleophilic solvent, or in the presence of a
PdII-salt as a catalyst is required for thermal rearrangement
The title heterocycles were chosen as a starting materials
for the present study because of the diverse pharmacological
activities of the indole [17-24] and oxadiazole derivatives
[25-29] and of compounds containing both heterocycles [30-
32]. The indole derivatives exhibit pharmacological
activities, such as antitumor [17], anticonvulsant,
tranquilizing [18], antibacterial, antifungal, antiviral [19],
antiinflammatory [20], and immunosuppressive [21]
activities. They are also used as physiological modulators, as
inhibitors of human liver glycogen phosphorylase [22],
aromatase [23], and human cytosolic phospholipase A2ꢁ
o
of the allylthiothiazole in bromobenzene (>265 C) to give
the N-allyl analog with a very low yield. However, a similar
*Address correspondence to this author at the International Center for
Chemical and Biological Sciences, H.E.J. Research Institute of Chemistry,
Karachi University, Karachi 75270, Pakistan; Tel: +203-4246601;
Fax: +203-4271360; E-mail: eelashry60@hotmail.com
1570-1786/09 $55.00+.00
© 2009 Bentham Science Publishers Ltd.

Synthesis of New Functionalized
Letters in Organic Chemistry, 2009, Vol. 6, No. 6
463
N
NH
X
S
O
N
H
1
R
X
R
TEA/acetone
K2CO3/
acetone
or KOH/EtOH
R
N
N
N
N
R
S
S
O
O
N
N
H
H
3
2
R
a
b
c
d
e
f
g
h
i
-CH2OH
-CH2CH2OH
-CH(OH)CH3
-CH(OCH2CH3)2
-COPh
-COOC(CH3)3
-CN
-COOC2H5
-CH2CH3
j
-CH2CH2CH3
k -CH=CH2
-Ph
l
m -CH2(CH2)9CH3
n -COOH
X= Br for all alkyl halides, except for g and h, X= Cl
Scheme 1. Synthesis of S- and N-alkylated indolyloxadiazoles.
Table 1. Yields of Alkylation Products of 1
[24]. The 1,3,4-oxadiazoles have showed anti-inflammatory,
analgesic [25], antimicrobial [26], antimalarial [27],
antiproliferative [28], and antituberculosis activities [29].
Heterocycles possessing indole linked to 1,3,4-oxadiazole
show efficient anti-inflammatory [30,31], and antibacterial
[32] activities.
Compound
Et3N Yield (%)
K2CO3 Yield (%)
2a
2b
2c
2d
2e
2f
96
96
98
73
97
65
60
63
88
86
91
90
60
63*
–
RESULTS AND DISCUSSION
The thione 1 was prepared according to a reported
procedure [33]. Its 13C NMR spectrum showed a signal at ꢀc
176.8 ppm for a C=S, and its 1H NMR spectrum showed two
singlets at ꢀ 11.16 and 14.75 ppm corresponding to the two
N-H protons. This indicates the existence of 1 in the thione
rather than the thiol tautomer. Furthermore, the N-H signal at
ꢀ 11.16 ppm showed a coupling through space with a signal
at ꢀ 7.55 ppm in the NOESY-spectrum confirming its
assignment to the indole N-H; other protons and carbons
could be assigned by the COSY and HMQC spectra.
2g
2h
2i
75
79
-
2j
2k
2l
-
The thione 1 was alkylated with a set of alkyl halides in
acetone containing TEA at room temperature. Only one
molar equivalent of the alkyl halide was consumed by 1
giving regioselectively S-alkylated products 2a-l in very
good yields (Scheme 1). The absence of a 13C NMR signal in
the range ꢀc 175-177 ppm and the presence of that carbon in
the range ꢀc 162-164 ppm as well as the absence of the
oxadiazole N-H signal in the 1H NMR spectra of all products
confirmed the assignments.
2m
2n
3i
60
-
25
21
40
3j
–
3m
40
*Alkylation mediated with KOH followed by acidification with HCl.

464 Letters in Organic Chemistry, 2009, Vol. 6, No. 6
El Ashry et al.
Alkylation of 1 with 1-bromopropane, 1-bromobutane
and 1-bromoundecane in acetone containing K2CO3 gave a
mixture of the N-alkylated 3i-j,m as well as the S-alkylated
derivatives 2i-j,m (Scheme 1). N-alkylation was deduced
from the 13C-NMR which showed a C=S signal in the range
ꢀc 175-176 ppm that was not in the spectra of the S-alkylated
derivatives. The NH signal in the 1H NMR spectra showed a
long range coupling with H-7 in the NOESY spectra
confirming its assignment as the indole NH. Alkylation of 1
with n-undecyl bromide in the presence of Et3N or K2CO3
yielded a mixture of S- and N-alkylated oxadiazoles 2m and
3m in 60 % and 40 % yield respectively. Alkylation of 1
with chloroacetic acid required heating in alcoholic NaOH
followed by acidification giving the acid 2n in a moderate
yield (Table 1).
and 6 in 82 % yield, respectively (Scheme 2). Disappearance
of the 1H NMR signal of the NH group confirmed its
allylation.
Benzylation of 1 with two molar equivalents of benzyl
bromide in presence of K2CO3 gave 7 in moderate yield.
Absence of the indole NH signal in 1H NMR, and its
coupling in the NOESY spectrum confirmed its benzylation
(Scheme 3). Attempted induction of the migration of the S-
benzyl group in the S,N-bis-benzyl 7 by fusion failed to give
8 (Scheme 3).
CONCLUSION
The acid scavenger required for the alkylation process
played a role in directing the alkylation to the sulfur or
nitrogen in 5-(1H-indol-2-yl)-1,3,4-oxadiazole-2(3H)-thione.
Thio-aza Claisen rearrangement of the 2-Allylsulfanyl-5-
(1H-indol-2-yl)-1,3,4-oxadiazole and 5-(1-allyl-1H-indol-2-
yl)-2-allylsulfanyl-1,3,4-oxadiazole to their respective 3-N-
allyl-oxadiazoles was obtained in high yield simply by their
fusion. The simplicity of this rearrangement will be of
potential value for further applications.
When the allylthioether 2k was subjected to fusion under
atmospheric conditions, an excellent yield of the rearranged
product 3k was obtained within 5 minutes, probably through
thio-aza-Claisen rearrangement in which the allyl group
migrates from sulfur to the ortho nitrogen functionality.
Similarly, S,N-bis-allyl 5 gave the N,N-bis-allyl 6 in high
yield. Thermal intramolecular [3,3]-sigmatropic reorganiza-
tion of the allyl group from sulfur to nitrogen may take place
via a six membered cyclic transition state 4, in a concerted
EXPERIMENTAL
General
six electron reorganization, and accompanied by
a
rearomatization yielding the N-allyl derivative 3k. The
appearance of a 13C NMR signal for C=S bond at ꢀc 175
ppm, while keeping the NH 1H NMR signal of the indole 3k
was strong evidence for the rearrangement. On allylation of
2k and 3k with allyl bromide in the presence of K2CO3, the
NH of the indole rings were allylated to give 5 in 70 % yield
Melting points were determined with a melt-temp
apparatus (SMP10) in open capillaries and are uncorrected.
TLC was performed on Merck silica gel 60 F254 with
1
detection by UV light absorption. H NMR spectra were
N
N
N
N
Fusion
S
S
O
O
N
H
N
H
2k
K2CO3,
acetone
Br
N
N
N
N
S
S
O
N
O
N
H
4
5
Fusion
N
N
N
N
Br
K2CO3, acetone
S
S
O
O
N
H
N
3k
6
Scheme 2. Thio-aza-Claisen rearrangement of S-allyl and S,N-bisallyloxadiazole.

Synthesis of New Functionalized
Letters in Organic Chemistry, 2009, Vol. 6, No. 6
465
N
NH
N
N
Br
Ph
Ph
S
S
K2CO3/acetone
O
O
N
N
H
1
Ph
7
Fusion
N
Ph
N
S
O
N
Ph
8
Scheme 3. Benzylation of the indolyloxadiazole thione 1.
recorded on avane Bruker NMR spectrometer at 300 or 400
MHz, whereas the 13C NMR was done on the same
instrument at 75 or 100 MHz, respectively, with TMS as
internal standard. Mass spectra were recorded on a Finnigan
(MAT312) and Jeol (JMS.600H), HRMS were recorded with
Thermo Finnegan (MAT 95XP). Solvents used were purified
by simple distillation.
(SCH2), 59.4 (CH2O), 104.8 (C-3), 112.2 (C-7), 120.3 (C-
5ind.), 120.7 (C-2ind.), 121.4 (C-4), 124.2 (C-6), 127.2 (C-3a),
137.7 (C-7a), 160.3 (C-5oxad.), 163.3 (C-2oxad.). HR-EIMS:
Calcd. for C12H11N3O2S [M]+ 261.0572; Found 261.0555.
2-(3-Hydroxyprop-1-ylsulfanyl)-5-(1H-indol-2-yl)-1,3,4-
oxadiazole (2b)
Recrystallized from EtOH to afford colorless crystals in
96 % yield; mp 178-180 oC, Rf 0.36 (19:1 CHCl3/MeOH). 1H
NMR (300 MHz, DMSO-d6): ꢀ 1.92 (m, 2H, CH2), 3.36 (t,
2H, J = 7.1 Hz, SCH2), 3.51-3.56 (m, 2H, CH2O), 4.65 (t,
5-(1H-indol-2-yl)-1,3,4-oxadiazole-2(3H)-thione (1)
Recrystallized from EtOH affording yellow shining
o
plates in 83 % yield; mp 266-268 oC (lit. [33] mp 262 C), Rf
1
0.3 (9:1 CHCl3/MeOH). H NMR (300 MHz, DMSO-d6): ꢀ
1H, J = 4.8 Hz, OH, D2O exchangeable), 7.09 (dd, 1H, J5,4
8.0, J5,6 = 7.4 Hz, H-5), 7.17 (s, 1H, H-3), 7.25 (dd, 1H, J5,6
=
=
7.14 (dd, 1H, J5,4 = 8.0, J5,6 = 7.3 Hz, H-5), 7.23 (s, 1H, H-3),
7.31 (dd, 1H, J6,5 = 7.3, J6,7 = 8.3 Hz, H-6), 7.54 (d, 1H, J7,6 =
8.3 Hz, H-7), 7.71 (d, 1H, J4,5 = 8.0 Hz, H-4), 11.16 (bs, 1H,
indole NH, D2O exchangeable), 14.75 (bs, 1H, oxadiazole
NH, D2O exchangeable). 13C NMR (75 MHz, DMSO-d6): ꢀ
105.3 (C-3), 112.2 (C-7), 120.0 (C-2), 120.5 (C-5ind.), 121.5
(C-4), 124.5 (C-6), 127.1 (C-3a), 137.8 (C-7a), 155.9 (C-
5oxad.), 176.8 (C=S). HR-EIMS: Calcd. for C10H7N3OS [M]+
217.0310; Found 217.0342.
7.4, J6,7 = 8.2 Hz, H-6), 7.46 (d, 1H, J6,7 = 8.2 Hz, H-7), 7.65
(d, 1H, J4,5 = 8.0 Hz, H-4), 12.20 (bs, 1H, indole NH, D2O
exchangeable). 13C NMR (75 MHz, DMSO-d6): ꢀ 29.3 (S-
CH2), 32.1 (CH2), 58.9 (CH2O), 104.8 (C-3), 112.2 (C-7),
120.3 (C-5ind.), 120.7 (C-2ind.), 121.4 (C-4), 124.2 (C-6),
127.2 (C-3a), 137.7 (C-7a), 160.3 (C-5oxad.), 163.2 (C-2oxad.).
HR-EIMS: Calcd. for C13H13N3O2S [M]+ 275.0728; Found
275.0713.
2-(2-Hydroxyprop-1-ylsulfanyl)-5-(1H-indol-2-yl)-1,3,4-
oxadiazole (2c)
General Procedure for synthesis of 2a-l
Recrystallized from EtOH to afford colorless crystals in
98 % yield; mp 196-197 C, Rf 0.452 (95:5 CHCl3/MeOH).
The appropriate alkyl halide (1.1 mmol) was added to a
well stirred mixture of 1 (1.0 mmol) and Et3N or K2CO3 (1.1
mmol) in dry acetone (10 ml) and stirring was continued
overnight. If necessary, the mixture was filtered, washed
thoroughly with acetone and acetone was evaporated in
vacuo. The residue was purified by recrystallization from the
appropriate solvent.
o
1H NMR (300 MHz, DMSO-d6): ꢀ 1.20 (d, 3H, J = 6.1 Hz,
CH3), 3.24 (dd, 1H, J = 13.2 Hz, J = 6.9 Hz, SCHa), 3.38
(dd, 1H, J = 13.2 Hz, J = 4.6 Hz, SCHb), 3.97-4.01 (m, 1H,
CH), 5.15 (d, 1H, J = 4.9 Hz, OH, D2O exchangeable), 7.09
(dd, 1H, J5,4 = 7.9, J5,6 = 7.3 Hz, H-5), 7.17 (s, 1H, H-3), 7.25
(dd, 1H, J5,6 = 7.3, J6,7 = 8.2 Hz, H-6), 7.46 (d, 1H, J = 8.2
Hz, H-7), 7.65 (d, 1H, J = 7.9 Hz, H-4), 12.20 (bs, 1H,
indole NH, D2O exchangeable). 13C NMR (75 MHz, DMSO-
d6): ꢀ 22.3 (CH3), 40.7 (SCH2), 64.8 (CH), 104.8 (C-3),
112.2 (C-7), 120.3 (C-5ind.), 120.7 (C-2ind), 121.4 (C-4),
124.2 (C-6), 127.2 (C-3a), 137.7 (C-7a), 160.3 (C-5oxad.),
163.5 (C-2oxad.). HR-EIMS: Calcd. for C13H13N3O2S [M]+
275.0728; Found 275.0713.
2-(2-Hydroxyeth-1-ylsulfanyl)-5-(1H-indol-2-yl)-1,3,4-
oxadiazole (2a)
Recrystallized from EtOH/n-hexane to afford colorless
crystals in 96 % yield; mp 167-169 oC, Rf 0.33 (19:1 CHCl-
1
3/MeOH/). H NMR (300 MHz, DMSO-d6): ꢀ 3.40 (t, 2H, J
= 6.2 Hz, SCH2), 3.73-3.79 (m, 2H, CH2O), 5.16 (t, 1H, J =
5.5 Hz, OH, D2O exchangeable), 7.09 (dd, 1H, J5,4 = 7.9, J5,6
= 7.3 Hz, H-5), 7.17 (s, 1H, H-3), 7.25 (dd, 1H, J6,5 = 7.3, J6,7
= 8.3 Hz, H-6), 7.46 (d, 1H, J6,7 = 8.3 Hz, H-7), 7.65 (d, 1H,
J4,5 = 7.9 Hz, H-4), 12.2 (bs, 1H, indole NH, D2O
exchangeable). 13C NMR (75 MHz, DMSO-d6): ꢀ 35.2
2-(2,2-Diethoxyeth-1-ylsulfanyl)-5-(1H-indol-2-yl)-1,3,4-
oxadiazole (2d)
Recrystallized from EtOH to afford colorless crystals in
o
73 % yield; mp 167-169 C, Rf 0.27 (1:3 EtOAc/n-hexane).

466 Letters in Organic Chemistry, 2009, Vol. 6, No. 6
El Ashry et al.
1H NMR (300 MHz, DMSO-d6): ꢀ 1.08 (t, 6H, J = 7.0 Hz, 2
CH3), 3.47-3.66 (m, 6H, 3 CH2), 4.80 (t, 1H, J = 5.1 Hz,
CH), 7.09 (t, 1H, J5,4 = 7.9, J5,6 = 7.4 Hz, H-5), 7.18 (s, 1 H,
H-3), 7.25 (dd, 1H, J6,5 = 7.5, J6,7 = 8.3 Hz, H-6), 7.46 (d,
1H, J6,7 = 8.3 Hz, H-7), 7.66 (d, 1H, J4,5 = 7.9 Hz, H-4), 12.2
(bs, 1H, indole NH). 13C NMR (75 MHz, DMSO-d6): ꢀ 15.1
(2 CH3), 35.4 (S-CH2), 62.1 (2 OCH2), 100.4 (CH), 104.9
(C-3), 112.2 (C-7), 120.3 (C-5ind.), 120 .7 (C-2ind.), 121.4 (C-
4), 124.2 (C-6), 127.2 (C-3a), 137.7 (C-7a), 160.40 (C-5oxad.),
162.9 (C-2oxad.). HR-EIMS: Calcd. for C16H19 N3O3S [M]+
333.1147; Found 333.1133.
2 H, H-3, H-5), 7.32 (dd, 1H, J5,6 = 7.2, J6,7 = 8.3 Hz, H-6),
7.57 (d, 1H, J6,7 = 8.3 Hz, H-7), 7.67 (d, 1H, J4,5 = 7.9 Hz, H-
4), 9.72 (bs,1H, indole NH). 13C NMR (75 MHz, CDCl3): ꢀ
14.1 (CH3), 34.5 (SCH2), 62.5 (OCH2), 106.4 (C-3), 112.1
(C-7), 120.6 (C-2ind.), 121.0 (C-5ind.), 121.9 (C-4), 125.7 (C-
6), 127.7 (C-3a), 137.7 (C-7a), 161.1 (C-5oxad.), 162.7 (C-
2oxad.), 167.3 (C=O). HR-EIMS: Calcd. for C14H13N3O3S
[M]+ 303.0678; Found 303.0682.
5-(1H-Indol-2-yl)-2-Propylsulfanyl-1,3,4-oxadiazole (2i)
Recrystallized from EtOH to afford colorless crystals in
88 % yield; mp 173-175 oC, Rf 0.32 (3:7 EtOAc/n-hexane).
1H NMR (300 MHz, CDCl3): ꢀ 1.01 (t, 3H, J = 7.3 Hz, CH3),
1.92 (m, 2H, CH2), 3.3 (t, 2H, J = 7.2 Hz, SCH2), 7.15-7.18
(m, 2H, H-3, H-5), 7.31 (dd, 1H, J5,4 = 7.9, J5,6 = 7.1 Hz, H-
6), 7.64-7.66 (m, 2H, H-4, H-7), 10.13 (bs,1H, indole NH).
13C NMR (75 MHz, CDCl3): ꢀ 13.2 (CH3), 22.8 (CH2), 34.6
(SCH2), 106.0 (C-3), 112.3 (C-7), 120.9 (C-2ind., C-5ind.),
121.8 (C-4), 124.9 (C-6), 127.7 (C-3a), 137.7 (C-7a), 160.7
(C-5oxad.), 164.4 (C-2oxad.). HR-EIMS: Calcd. for
C13H13N3OS [M]+ 259.0779; Found 259.0796.
5-(1H-Indol-2-yl)-2-Phenacylsulfanyl-1,3,4-oxadiazole (2e)
Recrystallized from DMF/EtOH to afford colorless
crystals in 97 % yield; mp 271-272 oC, Rf 0.79 (4:7 EtOAc/n-
hexane). 1H NMR (300 MHz, DMSO-d6): ꢀ 5.21 (s, 2H,
SCH2), 7.09 (dd, 1H, J5,4 = 8.0, J5,6 = 7.4 Hz, H-5), 7.14 (s,
1H, H-3), 7.25 (dd, 1H, J6,5 = 7.3, J6,7 = 8.2 Hz, H-6), 7.45
(d, 1H, J6,7 = 8.2 Hz, H-7), 7.59 (t, 2H, J = 8.2 Hz, Ph), 7.68
(d, 1H, J4,5 = 8.0 Hz, H-4 ), 7.73 (t, 1H, J = 7.3 Hz, Ph), 8.08
(d, 2H, J = 7.3 Hz, Ph), 12.22 (bs, 1H, indole NH). 13C NMR
(75 MHz, CDCl3): ꢀ 40.7 (SCH2), 104.9 (C-3), 112.2 (C-7),
121.3 (C-5ind.), 120.5 (C-2ind.), 121.4 (C-4), 124.3 (C-6),
127.2 (C-3a), 128.5, 128.9, 134.0, 135.0 (Ph), 137.7 (C-7a),
160.4 (C-5oxad.), 162.6 (C-2oxad.), 192.6 (C=O). HR-EIMS:
Calcd. for C18H13N3O2S [M]+ 335.07285; Found 335.0735.
2-Butylsulfanyl-5-(1H-indol-2-yl)-1,3,4-oxadiazole (2j)
Recrystallized from EtOH to afford colorless crystals in
o
86 % yield; mp 178-180 C, Rf 0.39 (3:7 EtOAc/n-hexane).
1H NMR (300 MHz, CDCl3): ꢀ 0.97 (t, 3H, J = 7.3 Hz, CH3),
1.47-1.55 (m, 2H, CH2), 1.79-1.89 (m, 2H, CH2), 3.32 (t, 2H,
J = 7.3 Hz, SCH2), 7.13-7.15 (m, 2H, H-3, H-5), 7.31 (dd,
1H, J6,5 = 7.2, J6,7 = 8.2 Hz, H-6), 7.57 (d, 1H, J6,7 = 8.2 Hz,
H-7), 7.67 (d, 1H, J4,5 = 7.9 Hz, H-4), 9.71 (bs,1H, indole
NH). 13C NMR (75 MHz, CDCl3): ꢀ 13.5 (CH3), 21.8 (CH2),
31.3 (CH2), 32.5 (SCH2), 105.9 (C-3), 111.9 (C-7), 120.9 (C-
2-(t-Butyloxycarbonylmethylsulfanyl)-5-(1H-indol-2-yl)-
1,3,4-oxadiazole (2f)
Recrystallized from EtOH to afford colorless crystals in
65 % yield; mp 209-211 oC, Rf 0.57 (3:7 EtOAc/n-hexane).
1H NMR (300 MHz, CDCl3): ꢀ 1.46 (s, 9H, 3 CH3), 4.03 (s,
2H, SCH2), 7.14-7.18 (m, 2H, H-3, H-5), 7.32 (dd, 1H, J 6,5
=
2ind., C-5ind.), 121.8 (C-4), 125.0 (C-6), 127.7 (C-3a), 137.5
7.3 Hz, J6,7 = 8.2 Hz, H-6), 7.5 (d, 1H, J6,7 = 8.2 Hz, H-7),
7.67 (d, 1H, J4,5 = 7.9 Hz, H-4), 9.3 (bs, 1H, indole NH). 13C
NMR (75 MHz, DMSO-d6): ꢀ 27.5 (3 CH3 ), 34.89 (SCH2),
82.06 [(CH3)3C], 104.9 (C-3), 112.2 (C-7), 120.4 (C-5ind.),
120.5 (C-2ind.), 121.5 (C-4), 124.3 (C-6), 127.2 (C-3a), 137.7
(C-7a), 160.6 (C-5oxad.), 162.2 (C-2oxad.), 166.6 (C=O). HR-
EIMS: Calcd. for C16H17N3O3S [M]+ 331.0991; Found
331.0995.
(C-7a), 160.6 (C-5oxad.), 164.4 (C-2oxad.). HR-EIMS: Calcd.
for C14H15N3OS [M]+ 273.0936; Found 273.0952.
2-Allylsulfanyl-5-(1H-indol-2-yl)-1,3,4-oxadiazole (2k)
Recrystallized from EtOH to afford colorless needles in
o
91 % yield; mp 164-166 C, Rf 0.37 (1:3 EtOAc/n-hexane).
1H NMR (300 MHz, CDCl3): ꢀ 3.94 (d, 2H, J = 6.9 Hz,
SCH2), 5.24 (d, 1H, Jcis = 10.0 Hz, -CH=CHH), 5.41 (dd, 1H,
2
Jtrans = 16.9 Hz, J = 1.0 Hz, -CH=CHH), 5.97-6.08 (m, 1H,
2-Cyanomethylsulfanyl-5-(1H-indol-2-yl)-1,3,4-oxadiazole
(2g)
CH=CH2), 7.13-7.18 (m, 2H, H-3, H-5), 7.31 (dd, 1H, J6,5
=7.1 Hz, J6,7 = 8.3 Hz, H-6), 7.63 (d, H, J6,7 = 8.3 Hz, H-7),
7.67 (d, 1H, J4,5 = 7.9 Hz, H-4), 9.9 (bs,1H, indole NH). 13C
NMR (75 MHz, CDCl3): ꢀ 35.4 (SCH2), 106.2 (C-3), 112.4
(C-7), 119.9 (-CH=CH2), 120.7 (C-2ind.), 120.9 (C-5ind.),
121.7 (C-4), 125.0 (C-6), 127.7 (C-3a), 131.7 (-CH=CH2),
137.8 (C-7a), 160.9 (C-5oxad.), 163.4 (C-2oxad.). HR-EIMS:
Calcd. for C13H11N3OS [M]+ 257.0623; Found 257.0622.
Recrystallised from EtOH to afford colorless crystals in
o
60 % yield; mp 264-265 C, Rf 0.22 (3:7 EtOAc/n-hexane).
1H NMR (300 MHz, DMSO-d6): ꢀ 4.52 (s, 2H, SCH2), 7.10
(dd, 1H, J5,4 = 8.0, J 5,6 = 7.3 Hz, H-5), 7.21 (s, 1H, H-3) 7.26
(dd, 1H, J5,6 = 7.3, J6,7 = 8.1 Hz, H-6), 7.47 (d, 1H, J6,7 = 8.1
Hz, H-7), 7.67 (d, 1H, J4,5 = 8.0 Hz, H-4), 12.29 (bs, 1H,
indole NH). 13C NMR (75 MHz, DMSO-d6): ꢀ 18.0 (SCH2),
105.4 (C-3), 112.3 (C-7), 116.9 (CN), 120.3 (C-2ind.), 120.4
(C-5ind.), 120.5 (C-2), 121.5 (C-4), 124.4 (C-6), 127.2 (C-3a),
137.8 (C-7a), 160.6 (C-5oxad.), 161.2 (C-2oxad.). HR-EIMS:
Calcd. for C12H8N4OS [M]+ 256.0419; Found 256.0418.
2-Benzylsulfanyl-5-(1H-indol-2-yl)-1,3,4-oxadiazole (2l)
Recrystallized from EtOH to afford colorless crystals in
90 % yield; mp 208-209 oC, Rf 0.40 (3:7 EtOAc/n-hexane).
1H NMR (400 MHz, CHCl3): ꢀ 4.53 (s, 2H, SCH2), 7.12
(s,1H, H-3), 7.16 (dd, 1H, J5,4 = 8.0, J5,6 = 7.5 Hz, H-5),
7.27-7.36 (m, 4H, H-6, Ph), 7.45 (d, 2H, J = 7.1 Hz, Ph),
7.49 (d, 1H, J7,6 = 8.3 Hz, H-7), 7.67 (d, 1H, J4,5 = 8.0 Hz, H-
4), 9.3 (bs, 1H, indole NH). 13C NMR (100 MHz, CHCl3): ꢀ
37.03 (SCH2), 106.1 (C-3), 112.0 (C-7), 120.8 (C-2ind.),
121.0 (C-5ind.), 121.86 (C-4), 125.1 (C-6), 127.7
(C-3a), 128.20, 128.88, 129.10, 135.4, (Ph), 137.50 (C-7a),
2-Ethoxycarbonylmethylsulfanyl-5-(1H-indol-2-yl)-1,3,4-
oxadiazole (2h)
Recrystallized from EtOH to afford colorless crystals in
63 % yield; mp 177-180 oC, Rf 0.39 (3:7 EtOAc/n-hexane).
1H NMR (300 MHz, CDCl3): ꢀ 1.28 (t, 3 H, J = 7.1 Hz,
CH3), 4.12 (s, 2 H, SCH2), 4.25 (q, 2 H, CH2), 7.15-7.18 (m,

Synthesis of New Functionalized
Letters in Organic Chemistry, 2009, Vol. 6, No. 6
467
160.78 (C-5oxad.), 163.60 (C-2oxad.). HR-EIMS: Calcd. for
3-Butyl-5-(1H-indol-2-yl)-2-thioxo-1,3,4-oxadiazole (3j)
C17H13N3OS [M]+ 307.0779; Found 307.0785.
It was isolated as minor product in 21 % yield along with
2j as a major product (79 %). Yellowish white solid; mp152-
154 °C Rf = 0.48 (3:7 EtOAc/n-hexane). 1H NMR (300 MHz,
CDCl3): ꢀ 1.0 (t, 3H, J = 7.3 Hz, CH3), 1.44 (m, 2H, CH2),
1.87 (m, 2H, CH2), 4.11 (t, 2H, J = 7.2 Hz, NCH2), 7.17 (dd,
1H, J5,6 = 7.4 Hz, J4,5 = 8.0 Hz, H-5), 7.21 (d, 1H, J = 1.4 Hz,
H-3), 7.33 (dd, 1H, J5,6 = 7.4 Hz, J6,7 = 8.3 Hz, H-6), 7.41 (d,
1H, J6,7 = 8.3 Hz, H-7), 7.68 (d, 1H, J4,5 = 8.0 Hz, H-4), 8.68
(bs,1H, indole NH). 13C NMR (75 MHz, CDCl3): ꢀ 13.6
(CH3), 19.7 (CH2), 29.5 (CH2), 49.2 (NCH2), 107.4 (C-3),
111.5 (C-7), 119.6 (C-2ind.), 121.4 (C-5ind.), 122.3 (C-4),
125.7 (C-6), 127.6 (C-3a), 137.3 (C-7a), 154.2 (C-5oxad.),
175.6 (C=S). HR-EIMS: Calcd. for C14H15N3OS 273.0936;
Found: 273.0931.
5-(1H-Indol-2-yl)-2-(undec-1-ylsulfanyl)-1,3,4-oxadiazole
(2m)
o
Yellowish white solid; 60 % yield, mp 134-136 C Rf
1
0.42 (15:85 EtOAc/n-hexane). H NMR (300 MHz, CDCl3):
ꢀ 0.86 (t, 3H, J = 6.5 Hz, CH3), 1.24 (bm, 14H, 7 CH2), 1.47
(m, 2H, CH2), 1.85 (m, 2H, CH2), 3.31 (t, 2H, J = 7.4 Hz,
SCH2), 7.15 (m, 2H, H-3, H-5), 7.31 (t, 1H, J = 7.6 Hz, H-6),
7.55 (d, 1H, J = 8.2 Hz, H-7), 7.67 (d, 1H, J = 7.9 Hz, H-4),
9.6 (bs,1H, indole NH). 13C NMR (400 MHz, CDCl3): ꢀ 14.1
(CH3), 22.7 (CH2), 28.6 (CH2), 29.0 (CH2), 29.3 (2 CH2),
29.5 (CH2), 29.6 (2 CH2), 31.9 (CH2), 32.8 (SCH2), 105.9
(C-3), 111.9 (C-7), 120.96 (C-2ind.), 120.99 (C-5ind.), 121.8
(C-4), 125.0 (C-6), 127.8 (C-3a), 137.5 (C-7a), 160.6 (C-
5
oxad.), 164.4 (C-2oxad.). HR-EIMS: Calcd for C21H29N3OS
5-(1H-Indol-2-yl)-2-thioxo-3-(undec-1-yl)-1,3,4-oxadiazole
(3m)
[M]+ 371.2031; Found 371.2033.
o
2-Carboxymethylsulfanyl-5-(1H-indol-2-yl)-1,3,4-
oxadiazole (2n)
Yellowish white solid; 40 % yield, mp 138-140 C, Rf
1
0.68 (15:85 EtOAc/n-hexane). H NMR (300 MHz, CDCl3):
ꢀ 0.86 (t, 3H, J = 6.6 Hz, CH3), 1.23 (bm, 16H, 8 CH2), 1.87
Chloroacetic acid (1.1 mmol) was added portionwise to a
well stirred solution of 1 (1.0 mmol) in ethanolic KOH (2 N)
and heated under reflux for 4 hours, then acidified by dil.
HCl. The precipitate was filtered and recrystallized from
ethanol to afford 2n as colorless crystals in 63 % yield, mp
233 oC, Rf 0.19 (CHCl3/EtOAc/MeOH 1:1:1.3).
1H NMR (300 MHz, DMSO-d6): ꢀ 4.24 (s, 2H, SCH2),
7.09 (dd, 1H, J5,4 = 7.9, J5,6 = 7.3 Hz, H-5), 7.22 (s,1H, H-3),
7.25 (dd, 1H, J6,5 = 7.3, J6,7 = 8.2 Hz, H-6), 7.46 (d, 1H, J7,6 =
8.2 Hz, H-7), 7.66 (d, 1H, J4,5 = 7.9 Hz, H-4), 12.24 (s,1H,
indole NH), 13.2 (bs, 1H, COOH). 13C NMR (75 MHz,
DMSO-d6): ꢀ 34.3 (SCH2), 104.9 (C-3), 112.2 (C-7), 120.3
(C-5ind.), 120.5 (C-2ind.), 121.4 (C-4), 124.2 (C-6), 127.2 (C-
3a), 137.7 (C-7a), 160.4 (C-5oxad.), 162.4 (C-2oxad.), 168.8
(COOH). HR-EIMS: Calcd. for C12H9N3O3S [M]+ 275.0365;
Found 275.0363
(m, 2H, CH2), 4.09 (t, 2H, J = 7.3 Hz, NCH2), 7.17 (t, 1H,
J4,5 = 8.0, J5,6 = 7.8 Hz, H-5), 7.21 (d, 1H, J = 1.4 Hz, H-3),
7.32 (dd, 1H, J5,6 = 7.8, J6,7 = 8.2 Hz, H-6), 7.41 (d, 1H, J6,7
= 8.2 Hz, H-7), 7.68 (d, 1H, J4,5 =8.0 Hz, H-4), 8.69 (bs,1H,
indole NH). 13C NMR (75 MHz, CDCl3): ꢀ 14.1 (CH3), 22.6
(CH2), 26.4 (CH2), 27.4 (CH2), 29.1 (CH2), 29.3 (CH2), 29.4
(CH2), 29.5 (CH2), 29.56 CH2), 31.9(CH2) 49.5 (NCH2),
107.4 (C-3), 111.5 (C-7), 119.7 (C-2ind.), 121.4 (C-5ind.),
122.3 (C-4), 125.6 (C-6), 127.6 (C-3a), 137.3 (C-7a), 154.2
(C-5oxad..), 175.6 (C=S). HR-EIMS: Calcd. for C21H29N3OS
[M]+ 371.2031; Found 371.2033.
3-Allyl-5-(1H-indol-2-yl)-2-thioxo-1,3,4-oxadiazole (3k)
Compound 2k was fused till all the starting material
converted to 3k (5 minutes as monitored by TLC). The
product was recrystallized from EtOH to afford 3k as
colorless needles in 89 % yield; mp 195-197 oC, Rf 0.49 (1:3
1
EtOAc/n-Hexane). H NMR (300 MHz, CDCl3): ꢀ 4.72 (d,
Alkylation of 1 in the presence of K2CO3
2H, J = 6.1 Hz, NCH2), 5.36-5.43 (m, 2H, -CH=CH2), 5.90-
6.37 (m, 1H, -CH=CH2), 7.18 (dd, 1H, J5,4 = 8.0, J5,6 = 7.1
The alkyl bromide (1.1 mmol) was added portionwise to
a well stirred mixture of 1 (1.0 mmol) and K2CO3 (1.1
mmol), in dry acetone (10 ml) and stirring was continued
overnight. The mixture was filtered, washed thoroughly with
acetone and the acetone solution was evaporated in vacuo.
The residues were purified by flash column chromatography
(n-hexane/EtOAc 19:1).
Hz, H-5), 7.22 (s, 1H, H-3), 7.33 (dd, 1H, J6,5 = 7.1 , J6,7
=
8.2 Hz, H-6), 7.40 (d, H, J6,7 = 8.2 Hz, H-7), 7.62 (d, 1H, J4,5
= 8.0 Hz, H-4), 8.7 (bs,1H, indole NH). 13C NMR (75 MHz,
CDCl3): ꢀ 51.74 (NCH2), 107.6 (C-3), 111.6 (C-7), 119.5 (C-
2ind.), 120.6 (-CH=CH2), 121.5 (C-5ind.), 122.3 (C-4), 125.8
(C-6), 127.6 (C-3a), 129.2 (-CH=CH2), 137.39 (C-7a), 154.4
(C-5oxad.), 175.7 (C=S). HR-EIMS: Calcd. for C13H11N3OS
[M]+ 257.0623; Found: 257.0618.
5-(1H-Indol-2-yl)-3-Propyl-2-thioxo-1,3,4-oxadiazole (3i)
It was isolated as minor product in 25 % yield along with
5-(1-Allyl-indol-2-yl)-2-allylsulfanyl- 1,3,4-oxadiazole (5)
2i as a major product (75 %). Yellowish white crystals; mp
o
1
183-185 C Rf 0.48 (3:7 EtOAc/n-hexane). H NMR (300
MHz, CDCl3): ꢀ 1.02 (t, 3 H, J = 7.4 Hz, CH3), 1.88-1.96 (m,
2H, CH2), 4.08 (t, 2 H, J = 7.2 Hz, NCH2), 7.15 (dd, 1H, J5,4
= 8.0 Hz, J5,6 = 7.1 Hz, H-5), 7.23 (s, 1H, H-3), 7.3 (dd, 1H,
J6,5 = 7.1, J6,7 = 8.3 Hz, H-6), 7.41 (d, 1H, J7,6 = 8.3 Hz, H-7),
7.68 (d, 1H, J4,5 = 8.0 Hz, H-4), 8.68 (bs,1H, indole NH). 13C
NMR (100 MHz, CDCl3): ꢀ 11.0 (CH3), 20.9 (CH2), 51.0
(NCH2), 107.4 (C-3), 111.6 (C-7), 119.6 (C-2), 121.4 (C-5),
122.3 (C-4), 125.7 (C-6), 127.6 (C-3a), 137.3 (C-7a), 154.2
(C-2ꢀ), 175.7 (C=S). HR-EIMS: Calcd. for C13H13N3OS [M]+
259.0779; Found 259.0763.
Allyl bromide (1.1 mmol) was added dropwise to a well
stirred mixture of 2k (1.0 mmol) and K2CO3 (2.0 mmol) in
dry acetone (10 ml) and stirring was continued overnight.
The mixture was filtered, washed thoroughly with acetone
and the acetone solution was evaporated in vacuo. The
residue was purified by flash column chromatography (n-
hexane/EtOAc 8: 2) to afford 5 as a colorless oil in 70 %
1
yield, Rf 0.58 (n-hexane/EtOAc 3:1). H NMR (300 MHz,
CDCl3): ꢀ 3.92 (d, 2H, J = 7.0 Hz, SCH2b), 4.87 (dd, 1H,
2
Jtrans = 17.1 Hz, J = 1.0 Hz, -C=CH2a), 5.10 (dd, 1H, Jcis
=
2
10.3 Hz, J = 1.0 Hz, -C=CH2a), 5.23 (d, 1H, J = 10.0 Hz,

468 Letters in Organic Chemistry, 2009, Vol. 6, No. 6
El Ashry et al.
-C=CH2b), 5.33-5.35 (m, 2H, NCH2a), 5.43 (dd, 1H, Jtrans
= 16.9 Hz, 2J = 1.3 Hz, -C=CH2b), 5.94-6.07 (m, 2H, –CHa,
-CHb), 7.13-7.18 (m, 2H, H-3, H-5), 7.29-7.39 (m, 2H, H-6,
H-7), 7.67 (d, 1H, J4,5 = 8.0 Hz, H-4). 13C NMR (75 MHz,
CDCl3): ꢀ 35.3 (SCH2b), 47.3 (NCH2a), 107.0 (C-3), 110.6
(C-7), 116.5 (=CH2a), 119.9 (=CH2b), 120.9 (C-5ind.), 122.0.7
(C-4), 122.3 (C-2ind.), 124.7 (C-6), 127.0 (C-3a), 131.7
(-CHb), 133.2 (-CHa), 139.0 (C-7a), 160.6 (C-5oxad.), 163.0
(C-2oxad.). HR-EIMS: Calcd. for C16H15N3OS [M]+ 297.0936;
Found 291.0923.
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(a) El Sayed, W. A.; Fathi, N. M.; Gad, W. A.; El Ashry, E. S. H. J.
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El Ashry, E. S. H.; Rashed, N.; Awad, L. F.; Ramadan, E. S.;
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(a) El Sayed, H. A.; Moustafa, A. H.; Haikal, A. Z.; Abdou, I. M.;
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El Ashry, E. S. H.; El Kilany, Y.; Nahas, N. M. Top Heterocycl.
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Hamid, H.; Louis, F. F.; Khattab, Sh. A. N.; Aouad, M. R.
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Ashry, E. S. H.; Atta, K. F.; Aboul-Ela, S.; Beldi, R. J. Carbohydr.
Chem., 2007, 26, 1-16.
3-Allyl-5-(1-Allyl-indol-2-yl)-2-thioxo-1,3,4-oxadiazole (6)
Allyl bromide (1.1 mmol) was added dropwise to a well
stirred mixture of 3k (1.0 mmol) and K2CO3 (1.0 mmol) in
dry acetone (10 ml) and stirring was continued overnight.
The mixture was filtered, washed thoroughly with acetone
and the acetone solution was evaporated in vacuo. The
residue was purified by flash column chromatography
(n-hexane/EtOAc 4:1) to yield 6 as colorless crystals in 82 %
o
1
yield, mp 91-93 C, Rf 0.673 (25:75 EtOAc/n-Hexane). H
NMR (400 MHz, CDCl3): ꢀ 4.72 (d, 2H, J = 6.0 Hz, NCH2c),
4.93 (d, 1H, Jtrans = 17.1 Hz, -C=CH2a), 5.08-5.13 (m, 3H,
-C=CH2a, NCH2a), 5.35-5.41 (m, 2H, -C=CH2c), 5.87-6.02
(m, 2H, –CHa, -CHc), 7.17 (m, 1H, H-5), 7.29 (s, 1H, H-3),
7.35 (m, 2H, H-6, H-7), 7.67 (d, 1H, J4,5 = 8.0 Hz, H-4). 13C
NMR (100 MHz, CDCl3): ꢀ 47.3 (NCH2a), 51.6 (NCH2c),
108.9 (C-3), 110.4 (C-7), 116.9 (=CH2a), 120.4
(=CH2c),120.8 (C-2ind.), 121.2 (C-5ind.), 122.4 (C-4), 125.4
(C-6), 126.8 (C-3a), 129.3 (-CHc), 132.7 (-CHa), 139.3
(C-7a), 154.3 (C-5oxad.), 175.2 (C=S). HRMS EI: Calcd. for
C16H15N3OS [M]+ 297.0936; Found 297.0933.
[5]
[6]
Mizutani, M.; Sanemitsu, Y. J. Org. Chem., 1983, 48, 4585-4589.
Kim, D. G.; Gavrilova, L. V. Chem. Heterocycl. Compd., 1997, 33,
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Mizutani, M.; Sanemitsu, Y.; Tamaru, Y.; Yoshida, ZI.
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Tamura, Y.; Kagotani, M.; Yoshida, Z. Tetrahedron Lett., 1981,
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5-(1-Benzyl-indol-2-yl)-2-benzylsulfanyl-1,3,4-oxadiazole
(7)
[12]
[13]
[14]
[15]
Ray, S.; Ghosh, S. J. Indian Chem. Soc., 2003, 80, 1037-1043.
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1447-1457.
Benzyl bromide (2.1 mmol) was added to a stirred
mixture of 1 (1.1 mmol) and K2CO3 (2.1 mmol) in dry
acetone (10 ml) and stirring was continued overnight. The
mixture was filtered, washed thoroughly with acetone and
the acetone solution was evaporated in vacuo. The residue
[16]
[17]
Takahata, H.; Banba, Y.; Mozumi, M.; Yamazaki, T. Heterocycles,
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Andreani, A.; Burnelli, S.; Granaiola, M.; Leoni, A.; Locatelli, A.;
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was purified by flash
column chromatography
(n-hexane/EtOAc 50:1) to afford 7 as white solid in 82 %
o
1
yield mp 148-150 C Rf = 0.66 (1:4 EtOAc/n-hexane). H
NMR (300 MHz, CHCl3): ꢀ 4.49 (s, 2H, SCH2), 5.97 (s, 2H,
NCH2), 7.05 (d, 2H, J = 7.3 Hz, 2H-Ph), 7.14-7.25 (m, 5H,
H-3, H-5, 3H-Ph), 7.28-7.36 (m, 5H, H-6, 4H-Ph), 7.41-7.44
(m, 2H , H-7, 1H-Ph), 7.69 (d, 1H, J4,5 = 8.0 Hz, H-4). 13C
NMR (75 MHz, CDCl3): ꢀ 36.8 (SCH2), 48.4 (NCH2), 107.3
(C-3), 110.8 (C-7), 120.9 (C-5ind.), 122.0 (C-4), 122.6
(C-2ind.), 124.9 (C-6), 126.5 (2C-Ph), 127.1 (C-3a), 127.2
(1C-Ph), 128.1 (1C-Ph), 128.5 (3C-PH), 128.8 (2C-PH),
129.1 (1C-PH), 135.4 (1 C-PH), 137.5 (C-7a), 139.3
(1C-PH), 160.6 (C-5oxad.), 163.2 (C-2oxad.). HR-EIMS: Calcd.
for C24H19N3OS 397.1249; Found 397.1261.
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support from the Higher Education Commission (HEC)
Pakistan (Project No. 20-697/R&D/06/38) is highly
appreciated.

Synthesis of New Functionalized
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