Synthesis and evaluation of novel 4-nitropyrrole-based 1,3,4-oxadiazole derivatives as antimicrobial and anti-tubercular agents

Article abstract of DOI:10.1016/j.ejmech.2013.09.039

We report synthesis and antimicrobial evaluation of 42 novel 4-nitropyrrole-based 1,3,4-oxadiazoles. The synthesized molecules were evaluated for anti-bacterial, anti-fungal and anti-tubercular activities. Promisingly, most of the compounds showed equal o

Full text of DOI:10.1016/j.ejmech.2013.09.039

European Journal of Medicinal Chemistry 70 (2013) 49e58
Contents lists available at ScienceDirect
European Journal of Medicinal Chemistry
journal homepage: http://www.elsevier.com/locate/ejmech
Original article
Synthesis and evaluation of novel 4-nitropyrrole-based 1,3,4-
oxadiazole derivatives as antimicrobial and anti-tubercular agents
,
1
1
*
Rajesh A. Rane , Pavankumar Bangalore , Sheetal D. Borhade, Preeti K. Khandare
SPP School of Pharmacy and Technology Management, NMIMS University, Vile Parle, Mumbai, Maharashtra 400056, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 4 May 2013
Received in revised form
We report synthesis and antimicrobial evaluation of 42 novel 4-nitropyrrole-based 1,3,4-oxadiazoles. The
synthesized molecules were evaluated for anti-bacterial, anti-fungal and anti-tubercular activities.
Promisingly, most of the compounds showed equal or more potency than standard ciprofloxacin against
Staphylococcus aureus, Bacillus subtilis and Escherichia coli. Compound 5e exhibited highest anti-
30 August 2013
Accepted 18 September 2013
Available online 2 October 2013
tubercular activity (0.46
tivity (1.56 g/mL) compared to standard Amphotericin-B was shown by most of the compounds. All the
N-methylated compounds showed more potent to equal activity against MSSA (MIC 0.39e1.56 g/mL)
and MRSA (MIC 0.78e1.56 g/mL). All compounds were tested for mammalian cell toxicity using VERO
cell line and were found to be non-toxic.
mg/mL) close to that of standard Isoniazid (0.40 mg/mL). Equal antifungal ac-
m
m
Keywords:
m
4-Nitropyrrole
1,3,4-Oxadiazole
Antimicrobial agent
Antifungal agent
Ó 2013 Elsevier Masson SAS. All rights reserved.
Anti-tubercular agent
1
. Introduction
were reported for 4-nitropyrrol-2-carboxaldehyde derivatives by
Colwell et al. [19]. Krajewska and Midura-Nowaczek [20] synthe-
sized and tested 4-nitropyrrole based-chloramphenicol derivative
1,3,4-Oxadiazole is an important class of heterocyclic bioactive
compounds [1]. The widespread use of them as a scaffold in me-
dicinal chemistry establishes this moiety as a member of the
privileged structures. Differently substituted 1,3,4-oxadiazoles have
been found to exhibit anti-inflammatory [2], hypoglycemic [3],
anti-anxiety [4], antidepressant [5], anti-proliferative [6], anti-
fungal [7,8], antibacterial [9] and anti-tubercular activities [10,11].
Moreover, 1,3,4-oxadiazole heterocycles are very good bioisosteres
of amides and esters, which contribute substantially to increasing
pharmacological activity by participating in hydrogen bonding in-
teractions with the receptors.
Natural nitropyrroles are the metabolites of bacterium Actino-
sporangium vitaminophilium, [12] and Streptomyces sp. [13].
Recently nitropyrrole-based natural products and their derivatives
are reported for having potential antimicrobial activities [13e16].
For instance, N-substituted pyrrolomycin, a compound with 4-
nitropyrrole moiety have shown antifungal activity better than
clotrimazole [17], while anti-tubercular activity was reported for
pyrrolonitrins [18]. Anti-malarial and antimicrobial properties
for their antibacterial properties, where MIC of 0.8 mg/mL was re-
ported against Staphylococcus aureus (ATCC 12600). Etoposide an-
alogs of 4-nitropyrrole are reported to have potent anti-tumor
activity inhibiting DNA Topoisomerase II [21]. The antifungal and
antibacterial properties of 1,2,4-triazoles substituted with 4-
nitropyrrole scaffold was reported by Pourmorad and Shafiee [22]
(Fig. 1). Based on the observations, an attempt to design a series
of novel antimicrobial molecules by coupling 1,3,4-oxadiazole with
4-nitropyrrole moiety using molecular hybridization approach has
been put forward. We synthesized 4-nitropyrrole based 1,3,4-
oxadiazoles containing diverse set of aromatic and hetero-
aromatic substitutions and evaluated them for their anti-bacterial,
antifungal and anti-tubercular activities. Further we also evaluated
effect of N-methylation on antimicrobial and anti-tubercular ac-
tivity (Fig. 2).
2. Results and discussions
2.1. Chemistry
*
Corresponding author. Tel.: þ91 9224294690.
In the present work, the proposed molecules were synthesized
as shown in Scheme 1. Acetylation of pyrrole was done using
calculated amounts of trichloroacetyl chloride in diethyl ether as
E-mail addresses: rajeshrane_uict@yahoo.co.in, rajeshrane.uict@gmail.com
(
R.A. Rane).
1
These authors have contributed equally.
0223-5234/$ e see front matter Ó 2013 Elsevier Masson SAS. All rights reserved.
http://dx.doi.org/10.1016/j.ejmech.2013.09.039

50
R.A. Rane et al. / European Journal of Medicinal Chemistry 70 (2013) 49e58
Fig. 1. Literature reports on nitropyrrole containing molecules [12e22].
solvent. Addition of pyrrole to trichloroacetyl chloride was done
slowly over a period of 1e2 h using a dropping funnel. After the
complete addition of pyrrole, the solvent was evaporated using
rotary evaporator and the product was dried [11,23,24]. The formed
acetylated pyrrole was nitrated using fuming nitric acid in acetic
anhydride at ice-cold temperatures to give good yield of 4-nitro-2-
trichloroacetyl-1H-pyrrole [25e27]. The nitrated product was
converted to its hydrazide by treating with excess hydrazine hy-
drate in absolute alcohol and stirred for an hour to give 4-nitro-1H-
pyrrole-2-carbohydrazide [11,24]. The obtained carbohydrazide
when reacted with aromatic or heteroaromatic acids, in the
presence of phosphorous oxychloride under reflux conditions, gave
the final required compound 2-(4-nitro-1H-pyrrol-2-yl)-5-aryl-
1,3,4-oxadiazole [11]. Using N-methylpyrrole the same reaction
procedure was carried out to give 2-(4-nitro-1-methyl-pyrrole-2-
yl)-5-aryl-1,3,4-oxadizoles.
1
The synthesized compounds were characterized by H NMR, MS,
C NMR and IR whose results confirmed the proposed structures of
13
the synthesized molecules. The (M þ H)þ molecular ion peak of all
1
the compounds confirmed the respective molecular weights. In H
NMR spectra, the NH proton of pyrrole showed peak in the range of
d
d
d
3
13.6e13.3 ppm, while the NeCH protons resonated between
4.2e4.0 ppm. The aryl protons of the ring B resonated between
9-6 ppm. IR spectroscopy showed a peak ranging between 3130
ꢀ1
and 3142 cm confirming the NH stretch and nitro group gave two
sharp peaks at around 1498e1541 cm and 1393e1414 cm . The
C]N stretch of oxadiazole ring was observed between 1620 and
ꢀ1
ꢀ1
ꢀ
1
1
635 cm
.
2.2. Biological activity result
The synthesized molecules exhibited promising and encouraging
antibacterial, antifungal and anti-tubercular activities (Table 1).
Most of the compounds showed a broad spectrum of activity against
both gram-positive and gram-negative bacterial strains. All the
tested molecules showed moderate to high potency compared to
standard ciprofloxacin against gram-positive bacterium S. aureus
except 5c and 5s. Compounds 5p, 5r and 5u exhibited two-fold
activity (0.78
mg/mL) more than the standard ciprofloxacin. This
indicated that presence of substituted phenyl ring and heterocyclic
ring at ring B position is favorable and increasing the distance be-
tween ring A and ring B is unfavorable for activity against S. aureus.
All the N-methylated compounds showed two to three fold potent
Fig. 2. Design of 4-nitropyrrole-based 1,3,4-oxadiazoles using molecular hybridization
approach.

R.A. Rane et al. / European Journal of Medicinal Chemistry 70 (2013) 49e58
51
Scheme 1. Synthesis of 2-(4-nitro-pyrrol-2-yl)-5-aryl-1,3,4-oxadiazole derivatives.
activity (MIC range 0.78
standard ciprofloxacin (MIC-1.56
m
g/mLe0.39
m
g/mL) against S. aureus than
with three fold potency than standard ciprofloxacin (MIC 1.56
mL) followed by compounds 5n and 5r (0.78
m
g/
mg/mL) indicating presence of N-
m
g/mL) which
methyl group on pyrrole enhances the activity compared to their NH
free analogs. Three-fold superior activity was observed for com-
exhibited two fold superior potency. This indicated that presence of
heterocyclic rings or hydroxyl and nitro containing phenyl ring at
ring B position lead to improvement of activity against gram-
negative bacterium Escherichia coli. Compounds 5a, 5b, 5e, 5q, 5t,
pounds 6b, 6n, 6r and 6s (MIC 0.39
mg/mL) against S. aureus
revealing that presence of halogen atoms like chlorine and presence
of heterocyclic ring plays important role for activity against
S. aureus. Heterocyclic substitution containing halogen like chlorine
at ring B position is favorable for the activity against S. aureus (6b,
5u, 6a, 6b, 6e, 6r and 6s showed equivalent activity (MIC 1.56 mg/mL)
as that of standard ciprofloxacin against E. coli. Presence of halogens
like fluorine and chlorine at phenyl ring are proved to be important
for antibacterial activity against E. coli. Here analogous to above
observation, the protection of pyrrole nitrogen by methyl group was
found to have profound effect on the anti-bacterial activity. Two-
fold less activity against E. coli were shown by compounds 5c, 5d,
6
n, 6r and 6s). Compounds 6a, 6cem, 6oeq, 6t and 6u (0.78
exhibited two-fold superior activity than standard ciprofloxacin
MIC 1.56 g/mL). The NH free analogs 5a, 5b, 5deo, 5q and 5t (MIC
.56 g/mL) showed equal potency as that of standard ciprofloxacin
MIC 1.56 g/mL).
All the N-methylpyrrole containing analogs have shown potent
or equal (MIC range 0.78 g/mLe1.56 g/mL) against B. subtilis
compared to standard ciprofloxacin (MIC 1.56 g/mL). However
their NH free analogs showed two fold less potency than standard
ciprofloxacin except compounds 5a, 5e, 5p, 5q and 5r (MIC 1.56 g/
mL). Compounds 6a, 6e, 6r and 6s (MIC 0.78 g/mL) were found to
mg/mL)
(
1
(
m
m
m
5f, 5g, 5h, 5l, 5o, 5p, 6c, 6d, 6f, 6m, 6p and 6t (MIC 3.125 mg/mL)
compared to standard ciprofloxacin. The decrease in activity of
compounds 5c and 6c against E. coli compared to standard cipro-
floxacin indicates the presence of linker between ring A and ring B is
unfavorable for the activity. All compounds tested against Klebsiella
pneumoniae were found to be less active than standard ciprofloxacin
m
m
m
m
m
(MIC 1.56
100 g/mL. Compounds 6aeo and 6reu (MIC 12.5
6c, 6p and 6q (MIC 50 g/mL) showed better activity than their NH
mg/mL) with MIC values ranging between 12.5
mg/mL e
be two time more potent than standard indicating that the pres-
ence of halogen atoms like bromine, chlorine and fluorine on ring B
is beneficial for activity against Bacillus subtilis. Compound 6e
showed two-fold activity against B. subtilis compared to standard
ciprofloxacin indicating that presence of methyl linker between
ring A and ring B is favorable for activity. Compounds 5a, 5e and 5r
m
mg/mL), except
m
free pyrrole core indicating N-methylation of pyrrole core played an
important role in enhancing the antimicrobial activity against
K. pneumoniae.
The synthesized compounds when tested against Methicillin
Susceptible S. aureus (MSSA) showed good activity when compared
with Ciprofloxacin. All the N-methylated compounds 6aed, 6fej,
(
MIC 1.56 mg/mL) exhibited equal anti- B. subtilis activity compared
to standard ciprofloxacin. But when compared with their N-
methylated analogs, the activity was found to be lesser indicating
that protection of nitrogen in pyrrole core with methyl group is
favorable for activity against B. subtilis.
6meo and 6reu showed two fold potent activity (MIC 0.39
than the standard Ciprofloxacin (MIC ¼ 1.56 g/mL). Equivalent
activity (MIC 1.56 g/mL) as standard was observed in all the NH-
free pyrrole compounds, except 5q (MIC 3.125 g/mL) and N-
methylated compounds 6e, 6k, 6l, 6p and 6q (MIC 1.56 g/mL). The
mg/mL)
m
m
For activity against gram-negative bacterium E. coli, highest ac-
m
tivity was shown by compounds 6l and 6n (MIC values 0.39
mg/mL)
m

52
R.A. Rane et al. / European Journal of Medicinal Chemistry 70 (2013) 49e58
Table 1
Antimicrobial results (MIC in mg/mL) of synthesized 4-nitropyrrole-based 1,3,4-oxadiazoles.
Compound
S. aureusa
B. subtilisa
E. colia
K. pneumoniaea
MSSA
MRSA
C. albicansb
Antitubercular
activity
IC50
(m
M)d
c
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
r
1.56
1.56
3.125
1.56
1.56
1.56
1.56
1.56
1.56
1.56
1.56
1.56
1.56
1.56
1.56
0.78
1.56
0.78
3.125
1.56
0.78
0.78
0.39
0.78
0.78
0.78
0.78
0.78
0.78
0.78
0.78
0.78
0.78
0.78
0.39
0.78
0.78
0.78
0.39
0.39
0.78
0.78
1.56
1.56
1.56
1.56
3.125
3.125
1.56
3.125
3.125
3.125
6.25
6.25
6.25
3.125
6.25
0.78
3.125
3.125
1.56
0.78
6.25
1.56
1.56
1.56
1.56
3.125
3.125
1.56
3.125
6.25
6.25
6.25
6.25
6.25
0.39
3.125
0.39
6.25
3.125
6.25
1.56
1.56
3.125
6.25
1.56
25
25
100
25
25
25
25
25
25
25
25
25
25
25
25
25
25
12.5
25
1.56
1.56
1.56
1.56
1.56
1.56
1.56
1.56
1.56
1.56
1.56
1.56
1.56
1.56
1.56
1.56
3.125
1.56
1.56
1.56
1.56
0.39
0.39
0.39
0.39
1.56
0.39
0.39
0.39
0.39
0.39
1.56
1.56
0.39
0.39
0.39
1.56
1.56
0.39
0.39
0.39
0.39
1.56
3.125
3.125
3.125
3.125
3.125
3.125
3.125
3.125
3.125
3.125
3.125
3.125
3.125
3.125
3.125
3.125
3.125
1.56
3.125
3.125
3.125
1.56
1.56
1.56
1.56
1.56
1.56
1.56
1.56
1.56
1.56
1.56
1.56
1.56
1.56
1.56
1.56
1.56
0.78
0.78
1.56
1.56
3.125
3.125
3.125
25
0.81
3.4
190.4
329.1
220.5
317.8
620.1
429.2
198.6
170.0
409.2
532.4
328.9
279.1
498.5
281.2
229.3
369.5
418.2
226.5
423.3
374.7
380.3
302.8
743.0
202.5
611.2
244.6
298.9
314.6
177.4
281.1
319.5
98.3
3.125
3.125
3.125
1.56
23.7
12.5
0.46
13.5
26.8
5.4
34.0
62.7
e
3.125
3.125
3.125
3.125
3.125
3.125
3.125
3.125
3.125
3.125
1.56
3.125
3.125
6.25
1.56
12.5
3.125
25
1.56
1.56
12.5
1.56
1.56
1.56
1.56
1.56
1.56
1.56
1.56
1.56
1.56
0.78
1.56
1.56
1.56
0.78
1.56
1.56
1.56
3.125
3.125
3.125
3.125
3.125
3.125
3.125
3.125
3.125
3.125
3.125
1.56
1.56
1.56
3.125
3.125
3.125
0.78
1.56
1.56
1.56
0.78
1.56
1.56
1.56
1.56
1.56
1.56
1.56
1.56
1.56
1.56
1.56
1.56
0.78
0.78
1.56
1.56
0.72
1.8
97.2
64.8
42.8
87.1
15.7
56.3
2.1
56.8
12.8
24.0
51.8
35.6
8.6
s
t
25
25
12.5
12.5
50
u
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
r
12.5
12.5
12.5
12.5
12.5
12.5
12.5
12.5
12.5
12.5
12.5
12.5
50
37.4
84.6
32.0
e
e
e
2.6
e
169.6
269.0
327.5
119.2
190.5
520.8
208.3
387.1
308.0
109.4
NT
e
e
60.2
e
50
12.5
12.5
12.5
12.5
1.56
29.3
18.4
3.8
s
t
u
e
e
Standard
1.56
0.40
a
MIC values are determined by broth dilution method (two fold dilution).
MIC values are determined by agar dilution method (two fold dilution).
MIC values are determined by Resazurin micro titer assay (REMA).
Cytotoxic concentration of drugs in VERO cells; NT, not tested.
b
c
d
e
Standard e Ciprofloxacin for antibacterial, Ampotericin-B for antifungal and Isoniazid for anti-tubercular activities were used respectively.
synthesized compounds showed potent to equal activity when
Amphotericin-B (MIC 3.125 mg/mL). This indicated that N-methyl-
tested against Methicillin Resistant Staphylococcus aureus (MRSA)
ation of pyrrole core is favorable for activity against Candida albi-
cans. Overall strong antibacterial and antifungal spectrum shown
by compounds 6n and 6r indicated that the presence of heterocy-
clic moieties at ring B position and N-methylation of pyrrole core is
important for the antimicrobial activity.
strain with MIC ranging from 0.78
pounds 6r and 6s (MIC 0.78 g/mL) were found to be most potent
with 2-fold activity than the standard Ciprofloxacin (MIC 3.125 g/
mg/mL to 3.125 mg/mL. Com-
m
m
mL). This strengthens the fact that N-methylation is favorable to-
wards activity against Staphylococcus aureus.
Most of the compounds showed moderate to good activity
In the anti-fungal study, all the N-methylated compounds, other
against Mycobacterium tuberculosis (MIC range 0.46
mL) compared to the standard Isoniazid (MIC 0.40
pound 5e (MIC 0.46 g/mL) showed highest anti-tubercular activity
close to standard Isoniazid (MIC 0.40 g/mL). The presence of
halogen atom, fluorine, and a methyl linker between ring A and ring
B is strongly favored for anti-tubercular activity. Whereas the
N-methyl analog 6e, containing same substitution, showed
m
g/mLe97.2
mg/
than compound 6c (MIC 12.5
more potent activity (MIC range 0.78e1.56
C. ablicans than standard drug Amphotericin-B (MIC 3.125
Compounds 6n and 6r exhibited three-fold superior activity (MIC
.78 g/mL) than standard Amphortericin-B. This strengthens the
m
g/mL), showed two to three-fold
g/mL) against
g/mL).
mg/mL). Com-
m
m
m
m
0
m
fact that the heterocyclic substitutions at ring B position proved to
be important for the activity. All the N-methyl pyrrole compounds
comparatively less activity (MIC 8.6
methylation of nitrogen on pyrrole core is not favored for anti-
tubercular activity. Compound 5l (MIC 0.72 g/mL) showed
mg/mL) indicating that the
6
5
a, 6b, 6dem, 6oeq, 6seu and NH-free pyrrole compounds 5n and
r showed (MIC - 1.56 g/mL) two-fold better activity than stan-
g/mL). Compounds 5a, 5b, 5de
m, 5o, 5p and 5t showed antifungal activity equivalent to standard
m
m
dard Amphotericin-B (MIC 3.125
m
promising tubercular activity which can be attributed to the pres-
ence of two nitro substitution on phenyl ring. Compound 5a also

R.A. Rane et al. / European Journal of Medicinal Chemistry 70 (2013) 49e58
53
exhibited promising anti-tubercular activity (MIC 0.81
m
g/mL)
oil-heating system and were uncorrected. Analytical Thin Layer
Chromatography (TLC) was carried out on precoated plates SiO
(silica gel 60, F 254, Merck). FTIR spectra were recorded on Perkin
Elmer RX I spectrometer using KBr pellets. All the NMR spectra
were recorded on JEOL AL-300 FT-NMR spectrometer with DMSO-
d as solvent using Tetramethyl Silane (TMS) as internal reference.
6
Mass spectra were obtained on THERMO FINNINGAN LCQ advan-
tage max (LCMS).
strengthening the fact that presence of halogen at second position
of phenyl ring is favored for the activity. Among the halogen sub-
stitutions, fluorine substituted compound showed better anti-
tubercular activity compared to that substituted with bromine.
Corresponding N-methylated analogs exhibited less anti-
tubercular potency than their NeH free analogs. This gives an
insight that the N-methylation of pyrrole core is not favored for
anti-tubercular activity. Good anti-tubercular activity with MIC less
2
than 3.0
MIC 2.1
m
g/mL were shown by compounds 5m (MIC 1.8
m
g/mL), 5t
4.2. General procedure for synthesis of 2-pyrrolyl trichloromethyl
ketone 2a & 2b
(
mg/mL) and 6l (MIC 2.6 g/mL). Overall this study gave us a
m
glimpse that the presence of heterocyclic moieties like quinoline or
pyrrole and N-methylation of pyrrole core is favorable for anti-
bacterial and antifungal studies whereas presence of methyl linkers
between ring A and ring B and NeH free pyrrole core is strongly
favorable for the anti-tubercular activity.
The desired compound was synthesized as given in the litera-
ture procedure [11,23,24].
4.3. General procedure for synthesis of 2,2,2-trichloro-1-(4-nitro-
1H-pyrrol-2-yl)ethanone 3a & 2,2,2-trichloro-1-(1-methyl-4-nitro-
pyrrol-2-yl)ethanone 3b: [25e27]
All the compounds were further examined for toxicity (IC50) in a
mammalian VERO cell line at a concentration of 62.5
mg/mL. After
72 h exposure, viability was assessed on the basis of cellular con-
version of MTT into a formazan product using the Promega Cell
Titer 96 non-radioactive cell proliferation assay [33]. The com-
pounds were non-toxic as represented in Table 1 and their
mammalian cell cytotoxicity was found to be much higher than
their respective MICs.
The structure activity relational studies gives us a glimpse that
the N-alkylation of pyrrole core has shown better activity in terms
of antibacterial and antifungal activity and also against MSSA and
MRSA strains. But NH-free pyrrole has shown better activity when
tested against M. tuberculosis. The presence of substitutions like
halogens and heterocyclic substitutions helps to improved anti-
microbial activity profiles.
The reaction was carried out using the by dissolving appropriate
amounts (1 equiv) of 2a or 2b in acetic anhydride. The solution was
ꢁ
cooled to ꢀ10 C using ice-salt mixture. Calculated amount of
fuming nitric acid (1.2 equiv) was added to the reaction mixture
dropwise, slowly over a period of 1 h. The reaction was then stirred
for another 2 h in icebath, later removed and stirred for an hour at
room temperature. The completion of reaction was monitored
through TLC. The reaction mixture was poured over crushed ice and
allowed to precipitate. The precipitate was filter through vacuum
and the product was recrystallized using absolute alcohol or
methanol.
2,2,2-Trichloro-1-(4-nitro-1H-pyrrol-2-yl) ethanone 3a: M.P
ꢁ
1
77e178 C.
3
. Conclusion
2,2,2-Trichloro-1-(1-methyl-4-nitro-pyrrol-2-yl) ethanone 3b:
M.P.136e138 C.
ꢁ
The synthesized nitropyrrole containing 1,3,4-oxadiazoles were
tested for their antimicrobial and anti-tubercular activity. These
compounds showed promising antibacterial activity against
S. aureus, B. subtilis, E. coli, MRSA and MSSA. Highest anti-tubercular
4.4. General procedure for synthesis of 4-nitro-1H-pyrrole-2-
carbohydrazide 4a and 4-nitro-1-methyl-pyrrole-2-carbohydrazide
4b: [11,24]
activity was showed by compound 5e (0.46
mg/mL). Anti-tubercular
MIC values as low as 0.46 g/mL, 0.72 g/mL 0.81
m
m
m
g/mL and 1.8 g/
m
In a round bottom flask, equipped with sealed mechanical stir-
rer, 1 mol of trichloroethanone 3a or 3b derivative was added in
30 mL of ethanol and stirred until the entire solution becomes
homogeneous. To above mixture 2.5 equivalents (3e4 mL) Hydra-
zine hydrate (99 %v/v) was added and stirred at room temperature
till precipitate starts to appear. The whole reaction mixture was
poured over crushed ice. The obtained solid precipitate was filtered
by vacuum and dried. The precipitate was washed with hexane and
recrystallized from absolute alcohol.
mL for compounds 5e, 5l, 5a and 5m respectively indicated that
these can act as novel leads for development of newer anti-
tubercular drugs. Equal antifungal activity compared to standard
Amphotericin-B was shown by compounds 5n, 5r, 6a, 6b, 6dem,
6
oeq and 6seu (1.56 mg/mL). The promising antibacterial, anti-
fungal and anti-tubercular results of the synthesized nitropyrrole-
based oxadiazoles including their non-toxicity for mammalian
cell have indicated their potential for further exploration and
modifications to get newer antimicrobial drug with better spec-
trum and potency.
4-Nitro-1H-pyrrole-2-carbohydrazide 4a: Yield: 67e69%; M.P.:
ꢁ
275.5e277 C.
1
-methyl-4-nitro-pyrrole-2-carbohydrazide 4b: Yield: 61e63%;
ꢁ
4
. Experimental protocol
M.P.: 220e221 C.
4.1. General
4.5. General procedure for synthesis of 2-(4-nitro-1H-pyrrol-2-yl)-
5-aryl-1,3,4-oxadiazole 5(aer) & 2-(1-methyl-4-nitro-pyrrol-2-yl)-
All reactions were carried out under an inert nitrogen atmo-
5-aryl-1,3,4-oxadiazole 6(aer) analogs: [11]
sphere under anhydrous conditions and by using Molecular sieve
ꢀ
00
(
4 A 1/16 pellets), Ethanol, methanol, n-hexane, ethylacetate and
The target compounds were synthesized using the procedure
given in literature by refluxing aryl/heteroaryl acids with carbo-
hydrazide 4a or 4b in phosphorous oxychloride. The reaction was
monitored with the help of TLC to check its completion. After
completion of reaction, the mixture was poured over crushed ice
and allowed to precipitate. The precipitate was vacuum filtered,
dried and recrystallized from methanol. Column chromatography
was done on using n-hexane: ethylacetate mixture (7:3). Solvent
ACN were freshly distilled from CaCl . All chromatographic solvents
2
were distilled before use. Silica gel of 60e120 mesh and 200e400
mesh were obtained for column and flash chromatography. Some of
the starting materials were obtained from S.D. Fine Pvt. Ltd., SRL,
Spectrochem/Aldrich and some of them were prepared in labora-
tory and used without further purification. All Melting Points (MP)
were recorded on Thermomik Compbell electronics, having

54
R.A. Rane et al. / European Journal of Medicinal Chemistry 70 (2013) 49e58
was evaporated invacuo using rotary evaporator to obtain pure
product.
NMR (100 MHz, DMSO-d
119.4, 114.9, 112.4, 111.4, 104.5, 55.3; Exact mass: 286.0707; MS m/z:
87.4092 (M NO), 241.4905
H)þ, 257.4458 (M
(M þ H ꢀ NO
6
): d 164.6, 161.2, 135.6, 130.9, 130, 127.3,
2
þ
þ
H
ꢀ
4
.5.1. 2-(2-Bromophenyl)-5-(4-nitro-1H-pyrrol-2-yl)-1,3,4-
oxadiazole (5a)
Yield: 87%; M.P: 319e321 C; IR (KBr) Vmax cm : 3135.65 (Ne
H), 1632.97 (C]N), 1540.85 & 1396.29 (NO
); 1H NMR (300 MHz,
13.6 (s, 1H, Pyrrole NH), 7.92 (s, 1H, Pyrrole H ), 7.88e
); C NMR (100 MHz,
164.57, 162.29, 136.11, 134.43, 131.81, 129.55, 129.08,
2
).
ꢁ
ꢀ1
4.5.7. 2-(4-Cyanophenyl)-5-(4-nitro-1H-pyrrol-2-yl)-1,3,4-
2
oxadiazole (5g)
ꢁ
ꢀ1
DMSO-d
6
):
):
d
d
5
Yield: 59%; M.P.: 262e264 C; IR (KBr) Vmax cm : 3136.74 (Ne
13
1
7.65 (m, 4H, Aryl), 7.42 (s, 1H, Pyrrole H
3
H), 1630.04 (C]N), 1537.07 & 1391.61 (NO
DMSO-d ): 13.42 (s, 1H, Pyrrole NH), 8.12 (s, 1H, Pyrrole H
7.54 (m, 4H, Aryl), 7.42 (s, 1H, Pyrrole H
DMSO-d ): 164.3, 135.6, 132.9, 130.8, 130.1, 128.4, 118.2, 112.4,
112.1, 104.7; Exact mass: 281.0599; MS m/z: 282.8103 (M þ H)þ,
52.7114 (M þ H ꢀ NO), 236.1332 (M þ H ꢀ NO ).
2
); H NMR (300 MHz,
), 7.82e
3
); C NMR (100 MHz,
DMSO-d
6
6
d
5
13
1
3
(
27.97, 123.88, 121.11, 111.85; Exact mass: 333.9702; MS m/z:
34.1273 (M NO), 288.1157
H)þ, 304.1711 (M
M þ H ꢀ NO
þ
þ
H
ꢀ
6
d
2
).
2
2
4.5.2. 2-(5-Chloro-1H-indol-2-yl)-5-(4-nitro-1H-pyrrol-2-yl)-
1
,3,4-oxadiazole (5b)
Yield: 63%; M.P.: 289e290 C; IR (KBr) Vmax cm : 3130.21 (Ne
4.5.8. 2-(2,6-Dimethoxyphenyl)-5-(4-nitro-1H-pyrrol-2-yl)-1,3,4-
ꢁ
ꢀ1
oxadiazole (5h)
1
ꢁ
ꢀ1
H), 1629.98 (C]N), 1541.11 & 1397.58 (NO
DMSO-d ): 13.52 (s, 1H, Pyrrole NH), 9.15 (s, 1H, Indole NH), 8.15
s, 1H, Pyrrole H ), 7.77e7.21 (m, 4H, indolyl), 7.43 (s, 1H, Pyrrole
2
); H NMR (300 MHz,
Yield: 81%; M.P.: 284e286 C; IR (KBr) Vmax cm : 3136.41 (Ne
1
6
d
H), 1623.43 (C]N), 1510.78 & 1395.12 (NO
DMSO-d ): 13.50 (s,1H, Pyrrole NH), 8.20 (s, 1H, Pyrrole H
7.62 (d, 3H, AreH), 7.35 (s, 1H, Pyrrole H ), 3.84e3.77 (2s, 6H,
164.2, 158.9, 135.6, 130.2,
130, 112.5, 108.1, 107.6, 104.1, 56.3; Exact mass: 316.0808; MS m/z:
317.1086 (M NO), 271.3305
H)þ, 287.5910 (M
M þ H ꢀ NO
2
); H NMR (300 MHz,
(
H
5
6
d
5
), 7.71e
13
3
), 6.97 (s, 1H, indol); C NMR (100 MHz, DMSO-d
6
):
d
164.2,
3
13
135.5,135.1,130.6,129.6,125.2,124.1,122.9,121.6,114.3,112.3,104.6,
3 6
OCH ); C NMR (100 MHz, DMSO-d ): d
1
3
00.2; Exact mass: 329.2952; MS m/z: 330.3032 (M þ H)þ,
00.2971 (M þ H ꢀ NO), 284.2977 (M þ H ꢀ NO
2
).
þ
þ
H
ꢀ
(
2
).
4.5.3. 2-(4-Hydroxy-3-methoxy-styryl)-5-(4-nitro-1H-pyrrol-2-
yl)-1,3,4-oxadiazole (5c)
Yield: 47%; M.P.: 280e282 C; IR (KBr) Vmax cm : 3135.12 (Ne
H), 1629.06 (C]N), 1539.67 & 1399.63 (NO
); 1H NMR (300 MHz,
DMSO-d ): 13.40 (s, 1H, Pyrrole NH), 7.93 (s,1H, Pyrrole H ), 7.69e
.54 (m, 3H, Aryl), 7.39 (s, 1H, Pyrrole H ), 6.65e6.83 (d, 2H, CH]
4.5.9. 2-(4-Methoxyphenyl)-5-(4-nitro-1H-pyrrol-2-yl)-1,3,4-
ꢁ
ꢀ1
oxadiazole (5i)
ꢁ
ꢀ1
2
Yield: 77%; M.P.: 340e342 C; IR (KBr) Vmax cm : 3134.66 (Ne
H), 1626.30 (C]N), 1498.35 & 1396.65 (NO
); 1H NMR (300 MHz,
DMSO-d ): 13.45 (s, 1H, Pyrrole NH), 8.15 (s, 1H, Pyrrole H ), 7.87e
7.71 (dd, 4H, AreH), 7.36 (s, 1H, Pyrrole H ), 3.86 (s, 3H, OCH
NMR (100 MHz, DMSO-d ): 164.2, 160.2, 135.2, 130.9, 129.2, 115.4,
114.6, 112.3, 104.5, 55.2; Exact mass: 286.0277; MS m/z: 287.3058
(M þ H)þ, 257.4401 (M þ H ꢀ NO), 241.5083 (M þ H ꢀ NO ).
6
d
5
2
7
3
6
d
5
1
3
13
CH), 6.21 (s, 1H, OH)3.92 (s, 3H, OCH
): 164.3, 160.9, 149.3, 147,7, 135.4, 133.9, 130.8, 130.2, 124.6,
22.3, 112.4, 116.4, 109.6, 104.2, 56.1; Exact mass: 328.0808; MS m/
z: 329.1792 (M þ H)þ, 299.7234 (M þ H ꢀ NO), 283.7240
M þ H ꢀ NO ).
3
); C NMR (100 MHz, DMSO-
3
3
);
C
d
6
d
6
d
1
2
(
2
4
.5.10. 2-(Isothiazol-5-yl)-5-(4-nitro-1H-pyrrol-2-yl)-1,3,4-
oxadiazole (5j)
Yield: 61%; M.P.: 190e192 C; IR (KBr) Vmax cm : 3134.06 (Ne
H), 1628.40 (C]N), 1503.06 & 1396.07 (NO
); 1H NMR (300 MHz,
DMSO-d ): 13.51 (s,1H, Pyrrole NH), 8.05 (s,1H, Pyrrole H ), 6.89e
6.75 (d, 2H, Thiazole), 7.43 (s, 1H, Pyrrole H ); C NMR (100 MHz,
DMSO-d ): 164.3, 161.2, 157.9, 147.2, 135.6, 130.2, 120.9, 104.6,
112.5; Exact mass: 263.0133; MS m/z: 264.1088 (M þ H)þ, 234.9213
(M þ H ꢀ NO), 218.0801 (M þ H ꢀ NO ).
4
.5.4. 2-(Piperidin-5-yl)-5-(4-nitro-1H-pyrrol-2-yl)-1,3,4-
oxadiazole (5d)
Yield: 28%; M.P.: 275e277 C; IR (KBr) Vmax cm : 3134.88 (Ne
H), 1628.23 (C]N), 1540.49 & 1399.45 (NO
); 1H NMR (300 MHz,
DMSO-d ): 13.38 (s, 1H, Pyrrole NH), 7.98 (s, 1H, Pyrrole H ), 7.42
s, 1H, Pyrrole H ), 3.15e2.42 (m, 4H, piperidinyl), 1.68e1.41 (m, 4H,
ꢁ
ꢀ1
ꢁ
ꢀ1
2
2
6
d
5
13
6
d
5
3
(
3
6
d
13
6
piperidinyl); C NMR (100 MHz, DMSO-d ): d 167.2, 164.7, 135.4,
130.6, 112.3, 104.9, 52.6, 48.2, 36.5, 30.8, 25.3; Exact mass:
2
2
63.1092; MS m/z: 264.8651 (M þ H)þ, 234.7096 (M þ H ꢀ NO),
218.1108 (M þ H ꢀ NO
2
).
4.5.11. 2-(5-Methylthiophen-2-yl)-5-(4-nitro-1H-pyrrol-2-yl)-
,3,4-oxadiazole (5k)
Yield: 55%; M.P.: 320e322 C; IR (KBr) Vmax cm : 3136.44 (Ne
H), 1630.98 (C]N), 1515.90 & 1395.98 (NO
); 1H NMR (300 MHz,
DMSO-d ): 13.35 (s, 1H, Pyrrole NH), 7.98 (s, 1H, Pyrrole H ), 7.45
(s, 1H, Pyrrole H ), 6.73 (d, 2H, Thiophen), 2.85 (s, 3H, CH
NMR (100 MHz, DMSO-d ): 164.6, 161.2, 135.6, 134.7, 130.5, 129.2,
127.8, 127.1, 112.3, 104.5, 15.3; Exact mass: 276.7031; MS m/z:
277.4982 (M NO), 231.6960
H)þ, 247.4095 (M
(M þ H ꢀ NO
1
ꢁ
ꢀ1
4.5.5. 2-(2-fluorobenzyl)-5-(4-nitro-1H-pyrrol-2-yl)-1,3,4-
oxadiazole (5e)
Yield: 56%; M.P.: 194e196 C; IR (KBr) Vmax cm : 3136.10 (Ne
2
ꢁ
ꢀ1
6
d
5
1
13
H), 1630.01 (C]N), 1540.97 & 1399.43 (NO
DMSO-d ): 13.45 (s, 1H, Pyrrole NH), 8.10 (s, 1H, Pyrrole H
.62 (m, 4H, AreH), 7.38 (s, 1H, Pyrrole H ), 2.54 (s, 2H, CH
NMR (100 MHz, DMSO-d ): 166.4, 164.8, 161.3, 135.9, 130.9, 130.3,
27.5, 124.3, 124, 115.3, 112.6, 104.9, 24.2; Exact mass: 287.2055; MS
m/z: 288.0692 (M þ H)þ, 258.9013 (M þ H ꢀ NO), 242.9665
M þ H ꢀ NO ).
2
); H NMR (300 MHz,
3
3
);
C
6
d
5
), 7.78e
6
d
1
3
7
3
2
);
C
6
d
þ
þ
H
ꢀ
1
2
).
(
2
4.5.12. 2-(2-Hydroxy-3,5-dinitrophenyl)-5-(4-nitro-1H-pyrrol-2-
yl)-1,3,4-oxadiazole (5l)
ꢁ
ꢀ1
4
.5.6. 2-(3-Methoxyphenyl)-5-(4-nitro-1H-pyrrol-2-yl)-1,3,4-
oxadiazole (5f)
Yield: 65%; M.P.: 273e275 C; IR (KBr) Vmax cm : 3136.90 (Ne
H), 1628.73 (C]N), 1537.78 & 1393.45 (NO
); 1H NMR (300 MHz,
DMSO-d ): 13.52 (s, 1H, Pyrrole NH), 7.92 (s,1H, Pyrrole H ), 7.92e
.74 (dd, 4H, AreH), 7.45 (s, 1H, Pyrrole H ), 3.92 (s, 3H, OCH C
Yield: 70%; M.P.: 250e252 C; IR (KBr) Vmax cm : 3132.58 (Ne
1
H), 1620.14 (C]N), 1528.29 & 1398.16 (NO
DMSO-d ): 13.58 (s, 1H, Pyrrole NH), 8.8e8.6 (d, 2H, AreH), 8.16
(s, 1H, Pyrrole H
(100 MHz, DMSO-d
130.1, 122.6, 113.6, 112.3, 112.7; Exact mass: 362.0244; MS m/z:
2
); H NMR (300 MHz,
ꢁ
ꢀ1
6
d
13
2
5
), 7.38 (s, 1H, Pyrrole H
3
), 6.28 (s, 1H, OH); C NMR
6
d
5
6
): d 167.9, 164.5, 157.3, 141.6, 138.2, 135.1, 130.6,
13
7
3
3
);

R.A. Rane et al. / European Journal of Medicinal Chemistry 70 (2013) 49e58
55
3
63.9177 (M
þ
H)þ, 333.8011 (M
þ
H
ꢀ
NO), 317.5119
246.0816 (M
(M þ H ꢀ NO
þ
H)þ, 216.7135 (M
þ
H
ꢀ
NO), 200.9103
(
M þ H ꢀ NO
2
).
2
).
4
.5.13. 2-(2-Hydroxy-3-nitrophenyl)-5-(4-nitro-1H-pyrrol-2-yl)-
4.5.19. 2-Phenyl-5-(4-nitro-1H-pyrrol-2-yl)-1,3,4-oxadiazole (5s)
ꢁ
ꢀ1
1,3,4-oxadiazole (5m)
Yield: 78%; M.P.: 309e310 C; IR (KBr) Vmax cm : 3134.72 (Ne
H), 1628.33 (C]N), 1541.58 & 1398.98 (NO
); 1H NMR (300 MHz,
DMSO-d ): 13.5 (s, 1H, Pyrrole NH), 8.1 (s, 1H, Pyrrole H ), 7.75e
7.55 (m, 5H, Aryl), 7.4 (s, 1H, Pyrrole H ). C NMR (100 MHz, DMSO-
): 164.3, 135.4, 133.7, 130.2, 129.2, 128.5, 127.4, 112.3, 104.7;
Exact mass: 256.2217; MS m/z: 257.2296 (M þ H)þ, 227.2235
(M þ H ꢀ NO), 211.2241 (M þ H ꢀ NO ).
ꢁ
ꢀ1
Yield: 34%; M.P.: 268e270 C; IR (KBr) Vmax cm : 3137.22 (Ne
2
1
H), 1628.62 (C]N), 1525.60 & 1398.93 (NO
DMSO-d ): 13.40 (s, 1H, Pyrrole NH), 8.16 (s, 1H, Pyrrole H
), 6.82 (s, 1H, AreH), 6.25 (s,
): 167.2, 164.6, 150.8, 144.2,
37.2, 135.1, 130.9, 128.6, 122.6, 113.1, 112.6, 104.1; Exact mass:
17.3069; MS m/z: 318.2144 (M þ H)þ, 288.5109 (M þ H ꢀ NO),
2
); H NMR (300 MHz,
6
d
5
13
6
d
5
), 8.0e
3
7.9 (d, 2H, AreH), 7.41 (s, 1H, Pyrrole H
3
d
6
d
1
1
3
2
H, OH); 13C NMR (100 MHz, DMSO-d
6
d
2
72.7124 (M þ H ꢀ NO
2
).
4.5.20. 2-(2-Hydroxyphenyl)-5-(4nitro-1H-pyrrol-2-yl)-1,3,4-
oxadiazole (5t)
ꢁ
ꢀ1
4
2
.5.14. 2-(6-Chloro-2-phenyl-quinolin-4-yl)-5-(4-nitro-1H-pyrrol-
-yl)-1,3,4-oxadiazole (5n)
Yield: 73%; M.P.: 231e234 C; IR (KBr) Vmax cm : 3136.26 (Ne
H), 1630.31 (C]N), 1539.21 & 1399.48 (NO
); 1H NMR (300 MHz,
DMSO-d ): 13.45 (s, 1H, Pyrrole NH), 8.12 (s, 1H, Pyrrole H ), 7.98e
7.73 (m, 4H, Aryl), 7.38 (s, 1H, Pyrrole H
(100 MHz, DMSO-d ): 167.4, 164.9, 157.4, 135.9, 130.6, 130, 126.4,
121.4, 117.9, 112.3, 108.9, 104.7; Exact mass: 272.0559; MS m/z:
2
ꢁ
ꢀ1
Yield: 49%; M.P.: 306e308 C; IR (KBr) Vmax cm : 3142.42 (Ne
H), 1624.97 (C]N), 1530.17 & 1383.92 (NO
); 1H NMR (300 MHz,
DMSO-d ): 13.5 (s, 1H, Pyrrole NH), 9.23 (s, 1H, quinoline H ), 8.21
s, 1H, Pyrrole H ), 8.28e7.75 (m, 4H, Quinolin), 7.67e7.51 (m, 5H,
Phenyl), 7.39 (s, 1H, Pyrrole H
164.2, 156.3, 143.2, 143, 139.2, 135.6, 135.1, 130.9, 130.4, 129.6,
6
d
5
13
2
3
), 6.25 (s, OH, 1H); C NMR
6
d
8
6
d
(
5
13
3
); C NMR (100 MHz, DMSO-d
6
):
273.2189 (M
(M þ H ꢀ NO
þ
H)þ, 243.2128 (M
þ
H
ꢀ
NO), 227.2134
d
2
).
127.9, 127.2, 127, 120.6, 112.3, 104.5, 104; Exact mass: 417.0699; MS
m/z: 418.6911 (M þ H)þ, 388.4053 (M þ H ꢀ NO), 372.8401
4.5.21. 2-(1-Phenylcyclopropyl)-5-(4-nitro-1H-pyrrol-2-yl)-1,3,4-
(
M þ H ꢀ NO
2
).
oxadiazole (5u)
ꢁ
ꢀ1
Yield: 51%; M.P.: 240e242 C; IR (KBr) Vmax cm : 3136.89 (Ne
H), 1634.31 (C]N), 1512.01 & 1398.93 (NO
); 1H NMR (300 MHz,
DMSO-d ): 13.42 (s, 1H, Pyrrole NH), 8.20 (s, 1H, Pyrrole H ), 7.41
(s, 1H, Pyrrole H ), 7.45e7.15 (m, 5H, AreH), 1.10e0.95 (m, 4H,
Cyclopropyl); C NMR (100 MHz, DMSO-d ): 164.5, 163.3, 146.5,
4
2
.5.15. 2-((1-Fluoronaphthalen-4-yl)methyl)-5-(4-nitro-1H-pyrrol-
-yl)-1,3,4-oxadiazole (5o)
Yield: 45%; M.P.: 228e230 C; IR (KBr) Vmax cm : 3137.01 (Ne
2
6
d
5
ꢁ
ꢀ1
3
1
13
H), 1633.63 (C]N), 1506.24 & 1399.01 (NO
DMSO-d ): 13.39 (s, 1H, Pyrrole NH), 8.15 (s, 1H, Pyrrole H
.49 (m, 6H, napthalene), 7.34 (s, 1H, Pyrrole H ), 4.12 (s, 2H, CH
164.6, 156.5, 143.8, 143.5, 139.1,
35.6, 131.6, 130.5, 129.1, 127.8, 127.5, 127.1, 123.6, 120.4, 112.1, 104.5,
04; Exact mass: 338.9001; MS m/z: 339.9081 (M þ H)þ, 308.9020
M þ H -NO), 292.9026 (M þ H - NO ).
2
); H NMR (300 MHz,
), 8.14e
);
6
d
6
d
5
135.6, 130.1, 128.1, 125.7, 125, 112.3, 104.7, 25.6, 16.8; Exact mass:
7
3
2
296.0909; MS m/z: 297.1962 (M þ H)þ, 267.1901 (M þ H ꢀ NO),
1
3
C NMR (100 MHz, DMSO-d
6
):
d
251.1907 (M þ H ꢀ NO
2
).
1
1
(
4.5.22. 2-(2-Bromophenyl)-5-(1-methyl-4-nitro-1H-pyrrol-2-yl)-
2
1,3,4-oxadiazole (6a)
ꢁ
ꢀ1
Yield: 68%; M.P.: 204e206 C; IR (KBr) Vmax cm : 1620.39 (C]
1
4
(
.5.16. 2-(Furan-2-yl)-5-(4-nitro-1H-pyrrol-2-yl)-1,3,4-oxadiazole
5p)
Yield: 68%; M.P.: 242e244 C; IR (KBr) Vmax cm : 3142.51 (Ne
N), 1528.52 & 1398.39 (NO
(s, 1H, Pyrrole H ), 7.72e7.35 (m, AreH, 4H), 7.34 (s, 1H, Pyrrole H
4.13 (s, 3H, Pyrrole NeCH
2
); H NMR (300 MHz, DMSO-d
6
):
d
8.20
),
164.5,
5
3
ꢁ
ꢀ1
13
3
); C NMR (100 MHz, DMSO-d
6
):
d
1
H), 1630.99 (C]N), 1510.72 & 1395.18 (NO
DMSO-d
2
); H NMR (300 MHz,
13.48 (s, 1H, Pyrrole NH), 7.95 (s, 1H, Pyrrole H ), 7.79e
); C NMR (100 MHz,
d 164.5, 157.2, 147.8, 138.3, 135.1, 130.2, 112.7, 104.8;
139.6,136.2,133.1,132.5,130.4,129.4,128.4,124.3,120.5,104.2, 27.4;
6
):
d
5
Exact mass: 347.9820; MS m/z: 348.99 (M þ H)þ, 318.9839
13
7.03 (m, 3H, furan), 7.31 (s, 1H, Pyrrole H
3
(M þ H ꢀ NO), 302.9845 (M þ H ꢀ NO
2
).
DMSO-d
6
):
Exact mass: 246.0389; MS m/z: 247.1189 (M þ H)þ, 217.9126
4.5.23. 2-(5-Chloro-1H-indol-2-yl)-5-(1-methyl-4-nitro-1H-
(
M þ H ꢀ NO), 201.8041 (M þ H ꢀ NO ).
2
pyrrol-2-yl)-1,3,4-oxadiazole (6b)
ꢁ
ꢀ1
Yield: 63%; M.P.: 184e186 C; IR (KBr) Vmax cm : 1606.20 (C]
1
4
.5.17. 2-(4-Nitro-1H-pyrrol-2-yl)-5-(thiophen-2-yl)-1,3,4-
oxadiazole (5q)
Yield: 51%; M.P.: 276e278 C; IR (KBr) Vmax cm : 3138.25 (Ne
H), 1621.14 (C]N), 1508.66 & 1399.07 (NO
); 1H NMR (300 MHz,
13.41 (s,1H, Pyrrole NH), 8.05 (s, 1H, Pyrrole H ), 7.70e
); C NMR (100 MHz,
164.3, 161.7, 135.6, 132.9, 131.8, 128.6, 128.0, 112.9,
N), 1526.04 & 1407.10 (NO
(s, 1H, Indol NH), 8.15 (s, 1H, Pyrrole H
7.41 (s, 1H, Pyrrole H ), 4.20 (s, 3H, Pyrrole NeCH
(100 MHz, DMSO-d ): 164.1, 136.5, 135.1, 133.6, 129.5, 125.6, 124.1,
122.9,121.8,114.6,104.3,100.3, 27.6; Exact mass: 343.0472; MS m/z:
344.6137 (M NO), 298.6082
H)þ, 314.6076 (M
(M þ H ꢀ NO
2
); H NMR (300 MHz, DMSO-d
6
): d 9.20
5
), 7.75e7.05 (m, 4H, indol),
ꢁ
ꢀ1
13
3
3
); C NMR
2
6
d
DMSO-d
6
):
):
d
5
13
7.53 (m, 3H, thiophene), 7.28 (s, 1H, Pyrrole H
3
þ
þ
H
ꢀ
DMSO-d
6
d
2
).
1
2
04.2; Exact mass: 262.0161; MS m/z: 263.2446 (M þ H)þ,
33.8071 (M þ H ꢀ NO), 215.9106 (M þ H ꢀ NO
2
).
4.5.24. 2-(4-Hydroxy-3-methoxy-styryl)-5-(1-methyl-4-nitro-1H-
pyrrol-2-yl)-1,3,4-oxadiazole (6c)
ꢁ
ꢀ1
4.5.18. 2-(4-Nitro-1H-pyrrol-2-yl)-5-(1H-pyrrol-2-yl)-1,3,4-
Yield: 43%; M.P.: 234e236 C; IR (KBr) Vmax cm : 1627.45 (C]
1
oxadiazole (5r)
Yield: 70%; M.P.: 264e266 C; IR (KBr) Vmax cm : 3131.69 (Ne
N), 1525.33 & 1399.38 (NO
(s, 1H, Pyrrole H ), 7.45e7.10 (m, 3H, AreH), 7.35 (s, Pyrrole H
6.85e6.74 (d, 2H, CH]CH), 6.23 (s, 1H, OH), 4.15 (s, 3H, Pyrrole Ne
2
); H NMR (300 MHz, DMSO-d
6
):
d
8.18
ꢁ
ꢀ1
5
3
, 1H),
1
H), 1626.87 (C]N), 1516.52 & 1406.48 (NO
DMSO-d ): 13.52 (s, 1H, NO -Pyrrole NH), 13.21 (s, 1H, pyrrole
NH), 8.09 (s, 1H, Pyrrole H ), 6.89e6.52 (m, 3H, pyrrole), 7.36 (s, 1H,
); C NMR (100 MHz, DMSO-d ): 164.9, 135.2, 130.5,
28.8, 120.2, 112.4, 106.8, 104.9; Exact mass: 245.0549; MS m/z:
2
); H NMR (300 MHz,
13
6
d
2
3 3 6
CH ), 3.89 (s, 3H, OCH ); C NMR (100 MHz, DMSO-d ): d 164.2,
5
160.2,149.3,147.1,136.6,133.5,133.1,130.5,124.8,124.6,122.6,116.6,
109.3, 104.2, 56.3, 27.1; Exact mass: 342.0964; MS m/z: 343.2108
(M þ H)þ, 313.2047 (M þ H ꢀ NO), 297.2053 (M þ H ꢀ NO
13
Pyrrole H
3
6
d
1
2
).

56
R.A. Rane et al. / European Journal of Medicinal Chemistry 70 (2013) 49e58
4
1
.5.25. 2-(Piperidin-5-yl)-5-(1-methyl-4-nitro-1H-pyrrol-2-yl)-
,3,4-oxadiazole (6d)
Yield: 27%; M.P.: 298e300 C; IR (KBr) Vmax cm : 1621.25 (C]
(s, 1H, Pyrrole H
zole), 4.15 (s, 1H, Pyrrole NeCH
164.3, 161.3, 157.6, 147.6, 136.5, 133.6, 124.9, 120.6, 104.4, 27.8;
Exact mass: 277.0270; MS m/z: 278.1095 (M þ H)þ, 248.1034
(M þ H ꢀ NO), 232.1040 (M þ H ꢀ NO ).
5
), 7.31 (s, 1H, Pyrrole H
3
), 6.73e6.61 (d, 2H, Thia-
13
3
); C NMR (100 MHz, DMSO-d ):
6
ꢁ
1
ꢀ1
d
N), 1520.93 & 1398.11 (NO
s, 1H, Pyrrole H ), 7.40 (s, 1H, Pyrrole H
CH ), 3.10e2.35 (m, 4H, piperidinyl), 1.85e1.43 (m, 4H, piperidinyl);
C NMR (100 MHz, DMSO-d ): 167.2, 164.5, 136.3, 133.6, 124.1,
04.6, 52.1, 48.2, 36.3, 30.2, 27.6, 25.4; Exact mass: 277.1175; MS m/
z: 278.2813 (M þ H)þ, 248.2752 (M þ H ꢀ NO), 232.2758
M þ H ꢀ NO ).
2
6
); H NMR (300 MHz, DMSO-d ): d 8.14
(
5
3
), 4.12 (s, 3H, Pyrrole Ne
2
3
13
6
d
4.5.32. 2-(5-Methylthiophen-2-yl)-5-(1-methyl-4-nitro-1H-pyrrol-
1
2-yl)-1,3,4-oxadiazole (6k)
ꢁ
ꢀ1
Yield: 60%; M.P.: 238e240 C; IR (KBr) Vmax cm : 1620.42 (C]
1
(
2
N), 1514.04 & 1401.04 (NO
s, 1H, Pyrrole H ), 7.44 (s, 1H, Pyrrole H
4.08 (s, 3H, Pyrrole NeCH
(100 MHz, DMSO-d ):
127.2, 124.1, 104.6, 27.6, 15.3; Exact mass: 290.0474; MS m/z:
2
); H NMR (300 MHz, DMSO-d
), 6.65 (d, 2H, thiophene),
3
), 2.81 (s, 3H, thiophen-CH ); C NMR
6
):
d 8.13
(
5
3
1
3
4
1
.5.26. 2-(2-Fluorobenzyl)-5-(1-methyl-4-nitro-1H-pyrrol-2-yl)-
,3,4-oxadiazole (6e)
Yield: 48%; M.P.: 278e280 C; IR (KBr) Vmax cm : 1629.67 (C]
3
6
d 164.3, 161.5, 136.9, 134.8, 133.5, 129.4, 127.9,
ꢁ
ꢀ1
1
N),1521.01 & 1397.56 (NO
H, Pyrrole H ), 7.85e7.54 (m, 4H, Aryl), 7.38 (s, 1H, Pyrrole H
s, 3H, Pyrrole NeCH
): 166.5,164.2,161.3, 136.3, 133.8, 130.6, 127.9, 124.8, 124.5,123.9,
15.6, 104.3, 27.6, 24.1; Exact mass: 302.0815; MS m/z: 303.0918
M þ H)þ, 273.0857(M þ H ꢀ NO), 257.0863 (M þ H ꢀ NO ).
2
); H NMR (300 MHz, DMSO-d
6
):
d
8.11 (s,
), 4.15
3 2
), 2.48 (s, 2H, CH ); C NMR (100 MHz, DMSO-
291.0385 (M
þ
H)þ, 261.0324 (M
þ
H
ꢀ
NO), 245.0330
1
(
d
1
5
3
(M þ H ꢀ NO
2
).
13
6
d
4.5.33. 2-(2-Hydroxy-3,5-dinitrophenyl)-5-(1-methyl-4-nitro-1H-
pyrrol-2-yl)-1,3,4-oxadiazole (6l)
ꢁ
ꢀ1
(
2
Yield: 71%; M.P.: 188e190 C; IR (KBr) Vmax cm : 1627.09 (C]
1
N), 1527.30 & 1399.17 (NO
8.62 (d, 2H, Aryl), 8.21 (s, 1H, Pyrrole H
6.22 (s, 1H, OH), 4.13 (s, 3H, Pyrrole NeCH
DMSO-d ): 167.9, 164.5, 157.6, 141.6, 138.2, 136.5, 133.2, 130.6,
124.1, 122.2, 113.6, 104.1, 27.5; Exact mass: 376.0404; MS m/z:
2
); H NMR (300 MHz, DMSO-d
6
):
d
8.69e
),
); C NMR (100 MHz,
4
.5.27. 2-(3-Methoxyphenyl)-5-(1-methyl-4-nitro-1H-pyrrol-2-
yl)-1,3,4-oxadiazole (6f)
Yield: 75%; M.P.: 220e222 C; IR (KBr) Vmax cm : 1629.10 (C]
5
), 7.42 (s,1H, Pyrrole H
3
13
3
ꢁ
ꢀ1
6
d
1
N), 1528.92 & 1403.77 (NO
s, 1H, Pyrrole H ), 7.83e7.24 (s, 4H, Aryl), 7.45 (s, 1H, Pyrrole H
.11 (s, 3H, Pyrrole NeCH
DMSO-d ): 164.3,161.2,136.5,133.5,130.5,127.5,124.6,119.9,114.6,
11.3, 104.6, 55.6, 27.6; Exact mass: 300.0859; MS m/z: 301.1043
M þ H)þ, 271.0982 (M þ H ꢀ NO), 255.0988 (M þ H ꢀ NO ).
2
); H NMR (300 MHz, DMSO-d
6
):
d
8.21
),
); C NMR (100 MHz,
(
4
5
3
377.2108 (M
(M þ H ꢀ NO
þ
H)þ, 347.2074 (M
þ
H
ꢀ
NO), 331.2053
1
3
3
), 3.85 (s, 3H, OCH
3
2
).
6
d
1
(
4.5.34. 2-(2-Hydroxy-3-nitrophenyl)-5-(1-methyl-4-nitro-1H-
2
pyrrol-2-yl)-1,3,4-oxadiazole (6m)
ꢁ
ꢀ1
Yield: 44%; M.P.: 268e270 C; IR (KBr) Vmax cm : 1625.72 (C]
1
4
1
.5.28. 2-(4-Cyanophenyl)-5-(1-methyl-4-nitro-1H-pyrrol-2-yl)-
,3,4-oxadiazole (6g)
Yield: 69%; M.P.: 300e302 C; IR (KBr) Vmax cm : 1625.92 (C]
N), 1522.26 & 1400.61 (NO
(s, 1H, Pyrrole H ), 8.02 (s, 1H, Aryl), 7.38 (s, 1H, Pyrrole H
6.61 (d, 2H, Aryl), 6.20 (s, 1H, OH), 4.02 (s, 3H, Pyrrole NeCH
NMR (100 MHz, DMSO-d ): 167.5, 164.2, 150.6, 144.3, 137.6, 136.6,
2
); H NMR (300 MHz, DMSO-d
6
):
d 8.22
5
3
), 6.79e
ꢁ
ꢀ1
13
3
);
C
1
N), 1524.76 & 1399.24 (NO
s, 1H, Pyrrole H ), 7.67e6.89 (m, 4H, Aryl), 7.32 (s, 1H, Pyrrole H
.08 (s, 3H, Pyrrole NeCH
36.5, 133.6, 132.5, 130.5, 128.6, 124.6, 118.5, 112.6, 104.6, 27.7; Exact
mass: 295.0705; MS m/z: 296.0715 (M
H)þ, 266.0654
2
); H NMR (300 MHz, DMSO-d
6
):
d
8.12
),
164.3,
6
d
(
4
1
5
3
133.2, 122.5, 128.6, 124.3, 113.2, 104.2, 27.8; Exact mass: 331.0553;
1
3
3
); C NMR (100 MHz, DMSO-d
6
):
d
MS m/z: 332.0571 (M þ H)þ, 302.0510 (M þ H ꢀ NO), 286.0516
(M þ H ꢀ NO
2
).
þ
(
M þ H ꢀ NO), 250.0660 (M þ H ꢀ NO
2
).
4.5.35. 2-(6-Chloro-2-phenyl-quinolin-4-yl)-5-(1-methyl-4-nitro-
1
H-pyrrol-2-yl)-1,3,4-oxadiazole (6n)
ꢁ
ꢀ1
4
2
.5.29. 2-(2,6-Dimethoxyphenyl)-5-(1-methyl-4-nitro-1H-pyrrol-
-yl)-1,3,4-oxadiazole (6h)
Yield: 39%; M.P.: 280e282 C; IR (KBr) Vmax cm : 1623.58 (C]
1
N), 1529.66 & 1413.04 (NO
(s, 1H, quinoline H ), 8.16 (s, 1H, Pyrrole H
Aryl), 7.45 (s, 1H, Pyrrole H ), 4.07 (s, 3H, Pyrrole NeCH
(100 MHz, DMSO-d ): 164.4,156.6,143.9,143.2,139.2,136.4,133.2,
2
); H NMR (300 MHz, DMSO-d
6
): d 9.21
ꢁ
ꢀ1
Yield: 81%; M.P.: 200e202 C; IR (KBr) Vmax cm : 1629.26 (C]
8
5
), 8.28e7.51 (m, 8H,
1
13
N), 1510.12 & 1410.25 (NO
s, 1H, Pyrrole H ), 7.42e7.04 (m, 3H, Aryl), 7.43 (s, 1H, Pyrrole H
.10 (s, 3H, Pyrrole NeCH
100 MHz, DMSO-d ): 164.3, 156.8, 136.9, 133.6130.5, 124.6, 108.6,
07.5, 104.5,56.2, 27.6; Exact mass: 330.0964; MS m/z: 331.1107
M þ H)þ, 300.0966 (M þ H ꢀ NO), 284.0972 (M þ H ꢀ NO ).
2
); H NMR (300 MHz, DMSO-d
6
):
d
8.12
),
); C NMR
3
3
); C NMR
(
4
(
1
5
3
6
d
1
3
3
), 3.85e3.68 (2s, 6H, OCH
3
131.6, 130.2, 129.5127.9, 127.6, 127.2, 124.3, 123.6, 120.3, 104.2, 104,
6
d
27.3; Exact mass: 431.0785; MS m/z: 432.9150 (M þ H)þ, 402.9089
(M þ H ꢀ NO), 386.9095 (M þ H ꢀ NO
2
).
(
2
4.5.36. 2-((1-Fluoronaphthalen-4-yl)methyl)-5-(1-methyl-4-nitro-
4
.5.30. 2-(4-Methoxyphenyl)-5-(1-methyl-4-nitro-1H-pyrrol-2-
yl)-1,3,4-oxadiazole (6i)
Yield: 87%; M.P.: 256e258 C; IR (KBr) Vmax cm : 1622.08 (C]
1H-pyrrol-2-yl)-1,3,4-oxadiazole (6o)
ꢁ
ꢀ1
Yield: 53%; M.P.: 158e160 C; IR (KBr) Vmax cm : 1626.25 (C]
ꢁ
1
ꢀ1
1
N), 1505.99 & 1403.87 (NO
(s, 1H, Pyrrole H ), 7.81e6.89 (m, 6H, Naphthalene), 7.43 (s, 1H,
Pyrrole H ), 4.42 (s, 2H, CH
(100 MHz, DMSO-d ): 166.2,164.3,154.5,136.9,134.5,133.9,130.2,
2 6
); H NMR (300 MHz, DMSO-d ): d 8.24
N), 1510.53 & 1401.97 (NO
s, 1H, Pyrrole H ), 7.78e7.21 (m, 4H, Aryl), 7.39 (s, 1H, Pyrrole H
.14 (s, 3H, Pyrrole NeCH
DMSO-d ): 164.3, 160.2, 136.6, 133.4, 129.5, 124.6, 115.6, 114.3,
04.6, 55.8, 27.9; Exact mass: 300.0859; MS m/z: 301.1043
M þ H)þ, 271.0982 (M þ H ꢀ NO), 255.0988 (M þ H ꢀ NO ).
2
); H NMR (300 MHz, DMSO-d
6
):
d
8.18
),
); C NMR (100 MHz,
5
13
(
4
5
3
3
2 3
), 4.12 (s, 3H, Pyrrole NeCH ); C NMR
1
3
3
), 3.78 (s, 3H, OCH
3
6
d
6
d
128.6, 126.3, 125.2, 124.1, 123.9, 123.4, 121.6, 112.2, 104.2, 29.1, 27.5;
1
(
Exact mass: 352.0972; MS m/z: 353.3921 (M þ H)þ, 323.3860
2
(M þ H ꢀ NO), 307.3866 (M þ H ꢀ NO
2
).
4
1
.5.31. 2-(Isothiazol-5-yl)-5-(1-methyl-4-nitro-1H-pyrrol-2-yl)-
,3,4-oxadiazole (6j)
Yield: 45%; M.P.: 178e180 C; IR (KBr) Vmax cm : 1625.04 (C]
4.5.37. 2-(Furan-2-yl)-5-(1-methyl-4-nitro-1H-pyrrol-2-yl)-1,3,4-
oxadiazole (6p)
ꢁ
1
ꢀ1
ꢁ
1
ꢀ1
Yield: 68%; M.P.: 192e194 C; IR (KBr) Vmax cm : 1631.56 (C]
N), 1526.62 & 1414.61 (NO
2
); H NMR (300 MHz, DMSO-d
6
):
d
8.16
2 6
N), 1512.81 & 1406.93 (NO ); H NMR (300 MHz, DMSO-d ): d 8.17

R.A. Rane et al. / European Journal of Medicinal Chemistry 70 (2013) 49e58
57
(
4
1
s, 1H, Pyrrole H
.08 (s, 3H, Pyrrole NeCH
57.1, 147.9, 138.7, 136.5, 133.2, 124.7, 115.0, 112.1, 104.8, 26.9; Exact
mass: 260.0546; MS m/z: 261.8015 (M
H)þ, 231.5905
5
), 7.86e6.69 (m, 3H, furan), 7.38 (s, 1H, Pyrrole H
3
),
were determined by broth dilution technique [28,29]. Ciprofloxacin
was used as a standard drug for antibacterial study. The lowest
concentration or the highest dilution required to arrest the growth
of bacteria was considered as minimum inhibitory concentration.
The MIC values are given in Table 1. The anti-fungal activity testing
of the synthesized nitropyrrole oxadiazoles was done on C. albicans
by agar dilution method using DMSO [30,31]. The nutrient broth,
which contained logarithmic serially two-fold diluted amount of
test compound and controls inoculated with approximately
13
); C NMR (100 MHz, DMSO-d ): d 164.9,
3 6
þ
(
M þ H ꢀ NO), 215.0901 (M þ H ꢀ NO
2
).
4
1
.5.38. 2-(1-Methyl-4-nitro-1H-pyrrol-2-yl)-5-(thiophen-2-yl)-
,3,4-oxadiazole (6q)
Yield: 51%; M.P.: 224e226 C; IR (KBr) Vmax cm : 1634.22 (C]
ꢁ
ꢀ1
1
4
4
N), 1501.88 & 1402.44 (NO
s, 1H, Pyrrole H ), 7.78e7.43 (m, 3H, thiophene), 7.32 (s, 1H, Pyrrole
), 4.01 (s, 3H, Pyrrole NeCH
164.1,161.9,136.6,133.8,132.2,131.0,128.7,128.1,124.4,104.1, 27.1;
Exact mass: 276.0317; MS m/z: 277.9104 (M þ H)þ, 247.8802
M þ H ꢀ NO), 231.1096 (M þ H ꢀ NO ).
2
); H NMR (300 MHz, DMSO-d
6
):
d
8.20
1.6 ꢂ 10 e6 ꢂ 10 CFU/mL, was used. The cultures were incubated
ꢁ
(
H
d
5
for 48 h at 35 C and the growth was monitored. The lowest con-
13
3
3
); C NMR (100 MHz, DMSO-d
6
):
centration (highest dilution) required to arrest the growth of fun-
gus was regarded as minimum inhibitory concentration (MIC).
The fungal activity of each compound was compared with
Amphotericin-B as standard drug. The minimum inhibitory con-
centration values for antifungal activity are given in Table 1.
The anti-tubercular activity of the compounds, against
(
2
4
1
.5.39. 2-(1-Methyl-4-nitro-1H-pyrrol-2-yl)-5-(1H-pyrrol-2-yl)-
,3,4-oxadiazole (6r)
Yield: 70%; M.P.: 180e182 C; IR (KBr) Vmax cm : 1625.71 (C]
V
M. tuberculosis H37R , was performed using Resazurin Microtiter
assay (REMA) [32]. Isoniazid was used as reference drug in the
ꢁ
ꢀ1
1
N), 1516.39 & 1409.11 (NO
2
); H NMR (300 MHz, DMSO-d
6
):
d
8.16
study. Homogenous mycobacterial (H37Rv) culture suspension was
5
(
s, 1H, Pyrrole H ), 7.78e7.43 (m, 3H, pyrrole), 7.32 (s, 1H, Pyrrole
5
seeded in microtitre plates at density of 10 cells per well in 100
mL
13
H
d
3
), 4.01 (s, 3H, Pyrrole NeCH
3
); C NMR (100 MHz, DMSO-d
6
):
of the Middlebrook 7H9 broth (Difco laboratories, Detroit, MI, USA)
and the test compounds were serially diluted directly on the plate.
The control received equivalent amount of DMSO. The plates were
164.6, 136.9, 133.2, 128.5, 124.7, 120.8, 112.5, 106.1, 104.4, 27.3;
Exact mass: 259.0705; MS m/z: 260.0816 (M þ H)þ, 230.7135
M þ H ꢀ NO), 214.9103 (M þ H ꢀ NO ).
ꢁ
(
2
incubated at 37 C for 7 days. Freshly prepared resazurin dye
(0.02%) was added and plates were again incubated for 48 h. MIC is
4
.5.40. 2-(2,4-Dichlorophenyl)-5-(1-methyl-4-nitro-1H-pyrrol-2-
yl)-1,3,4-oxadiazole (6s)
Yield: 57%; M.P.: 232e234 C; IR (KBr) Vmax cm : 1621.20 (C]
the lowest concentration at which complete inhibition was
observed and was determined by visual inspection (color change
from blue to pink).
ꢁ
ꢀ1
1
N), 1527.94 & 1401.15 (NO
s, 1H, Pyrrole H ), 7.92e7.59 (m, 3H, AreH), 7.44 (s, 1H, Pyrrole H
.10 (s, 1H, Pyrrole NeCH
36.6, 135.9, 135.6, 133.4, 133, 130.8, 130.1, 127.6, 124.5, 104.6, 27.6;
Exact mass: 337.9973; MS m/z: 338.9671 (M þ H)þ, 308.9610
M þ H ꢀ NO), 292.9616 (M þ H ꢀ NO ).
2
); H NMR (300 MHz, DMSO-d
6
):
d
8.12
),
164.2,
(
4
1
5
3
Acknowledgments
13
3 6
); C NMR (100 MHz, DMSO-d ): d
RAR thanks Professor R.S. Gaud for providing facility to carry out
these experiments. RAR also thanks Professor K. G. Akamanchi and
Dr. V. N. Telvekar for their constant support and encouragement.
(
2
4
.5.41. 2-((2-Trifluoromethoxy)phenyl)-5-(1-methyl-4-nitro-1H-
References
pyrrol-2-yl)-1,3,4-oxadiazole (6t)
ꢁ
ꢀ1
Yield: 76%; M.P.: 168e170 C; IR (KBr) Vmax cm : 1620.36 (C]
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[
[
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.03 (s, 3H, Pyrrole NeCH
64.5, 157.3, 136.3, 133.8, 130.2, 130, 129.2, 124.6, 116.3, 112.5, 104.8,
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M þ H ꢀ NO), 309.6247 (M þ H ꢀ NO ).
2
); H NMR (300 MHz, DMSO-d
), 7.55e7.05 (m, 4H, Aryl),
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1
2
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1
3
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d
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(
2
4.5.42. 2-(1H-Indol-2-yl)-5-(1-methyl-4-nitro-1H-pyrrol-2-yl)-
1,3,4-Oxadiazole (6u)
ꢁ
ꢀ1
Yield: 52%; M.P.: 310e312 C; IR (KBr) Vmax cm : 1605.42 (C]
1
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.40 (s, 1H, Pyrrole H ), 4.11 (s, 3H, Pyrrole NeCH
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21.6, 120.6, 119.1, 111.6, 104.6, 100.3, 27.6; Exact mass: 309.0862;
MS m/z: 310.3015 (M þ H)þ, 280.2954 (M þ H ꢀ NO), 264.2960
M þ H ꢀ NO ).
2
); H NMR (300 MHz, DMSO-d
6
): d 9.18
(
7
(
1
5
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