Synthesis and antioxidant activity study of carbothioamide and their corresponding thiazole derivatives

Article abstract of DOI:10.1002/jhet.4018

A novel series of 5-(p-(prop-2-ynyloxy)phenyl)-3-aryl-4,5-dihydropyrazole-1-carbothioamides 2a-f and functionalized 2-(3-(aryl)-5-(4-(prop-2-ynyloxy)phenyl)-4,5-dihydropyrazol-1-yl)-4-(3-arylsydnone-4-yl)thiazoles 4a-l were synthesized. The newly synthesi

Full text of DOI:10.1002/jhet.4018

Received: 23 December 2019
DOI: 10.1002/jhet.4018
Revised: 20 April 2020
Accepted: 24 April 2020
A R T I C L E
Synthesis and antioxidant activity study of carbothioamide
and their corresponding thiazole derivatives
Asma | Balakrishna Kalluraya
Chigahally Lakshmegowda Sharath
| Nagaraja Manju |
Department of Chemistry, Mangalore
Abstract
University, Mangalagangothri, India
A novel series of 5-(p-(prop-2-ynyloxy)phenyl)-3-aryl-4,5-dihydropyrazole-
-carbothioamides 2a-f and functionalized 2-(3-(aryl)-5-(4-(prop-2-ynyloxy)
Correspondence
1
Balakrishna Kalluraya, Department of
Chemistry, Mangalore University,
Mangalagangothri 574199, Karnataka,
India.
phenyl)-4,5-dihydropyrazol-1-yl)-4-(3-arylsydnone-4-yl)thiazoles 4a-l were syn-
thesized. The newly synthesized compounds were elucidated by analytical and
spectral analysis. From the single-crystal X-ray diffraction method, it was
observed that 2d crystallizes in a monoclinic crystal system with P21/n space
group. The compounds 2d crystallized with cell parameters a = 15.0614
Email: bkalluraya@gmail.com
o
o
(
19) Å, b = 6.0805 (7) Å, c = 20.903 (7) Å, α = 114.136 (6) , β = 110.709 (14) ,
o
3
γ = 96.553 (5) , V = 1790.6 (4) Å , Z = 4. From the Hirshfeld surface computa-
tional method, the major intercontacts present in these molecules are H…H
(31.6%), C…H (18.2%) and S…H (12.2%), respectively. The newly synthesized
compounds were tested for their ability to bleach 2,2'-diphenyl-1-
picrylhydrazyl (DPPH) radical using DPPH scavenging assay. Among the syn-
thesized compounds carbothioamide compounds 2c (90.7%) and 2b (89.8%)
exhibited good DPPH scavenging activity compared to the rest of the com-
pounds. Most of the synthesized carbothioamide molecules (2a-f) found to be
potent compared to the thiazole derivatives (4a-l).
[
9,10]
1
| INTRODUCTION
as they occur in some pharmaceuticals,
the contraceptive noretynodrel.
including
[
11]
Sydnone is the privileged member of the mesoionic
heteroaromatic compounds, which undergoes a wide
In synthetic and medicinal chemistry field, the combi-
nation of heterocyclic moiety such as such as sydnone,
pyrazoles, and thiazoles (Figure 1) have attracted a spe-
cial status due to their easy synthetic procedure and a
[
1]
variety of functionalization reaction.
well-known reaction of sydnone is intermolecular
,3-dipolar cycloaddition. In presence of dipolarophiles
like acetylene or ethylenic sydnone readily undergoes
One of the
[
12–16]
1
wide spectrum of pharmacological applications.
On the other hand, the effect of free radicals on
humans and in industrial sectors is increasing day by
day. The free radical not only cause premature ageing
and wrinkles but also is the primary cause of cancer and
[
2,3]
cyclo-addition which can be catalyzed thermally,
photochemically.
(
or
In particular, terminal acetylene
dipolarophile) is one of the best precursors for the
[
4,5]
[
17]
synthesis of various aromatic/heteroaromatic rings
through cycloaddition reaction, for example, azide-
other chronic diseases.
In industrial sectors like food,
petroleum and rubber and oil are also severely affected
[
6,7]
[8]
[18]
alkyne cycloaddition,
and Diels alder reaction,
by free radicals.
etc. Terminal acetylene is also found to be a very
important scaffold in the field of medicinal chemistry,
Over the past two decades, there has been growing
demand to find novel antioxidants to eradicate these
J Heterocyclic Chem. 2020;1–11.
wileyonlinelibrary.com/journal/jhet
© 2020 Wiley Periodicals LLC.
1

2
ASMA ET AL.
Simplification Combination
FIGURE 1 Some of the biologically potent molecules bearing sydnone, pyrazole, and thiazole rings
SCHEME 1 Synthetic route for
the synthesis of pyrazoline
carbothioamide 2a-f
problems, majorly many attempts were made to synthe-
size novel heterocyclic based antioxidants, in particular,
thiol (thiourea)-based heterocyclic compounds exhibited
2 | RESULT AND DISCUSSION
In the present work, we hereby report the synthesis of
functionalized acetylene bearing multicomponent hetero-
cyclic hybrid is as shown in Scheme 1 to Scheme 2. The
required starting compounds 5-(4-(prop-2-ynyloxy)phe-
nyl)-3-aryl-4,5-dihydropyrazole-1-carbothioamide (2a-f)
were synthesized by the base-catalyzed cyclization of
1-(p-substituted-phenyl)-3-(4-(prop-2-ynyloxy)phenyl)prop-
[19–21]
good radical scavenging activity.
Prompted by the above observations and in continua-
tion of our research work on the synthesis of biologically
active heterocycles, herein we report the total approach
towards the synthesis of thiazole-integrated pyrazole car-
rying sydnone with functionalized acetylene in a single
molecular frame and evaluated for their antioxidant
activity. Apart from antioxidant activity, intercontacts in
the crystal structure were quantified and visualized by
using Hirshfeld surface.
[22,23]
2-en-1-one
(1a-f) with thiosemicarbazide in presence
of catalytical amount of potassium hydroxide (Scheme 1).
The Hantzsch cyclization of precursor 2a-f and 4-
[24]
bromoacetyl-3-(aryl) sydnone (3a-b) in ethanol medium

ASMA ET AL.
3
SCHEME 2 Synthetic route for the synthesis of thiazole hybrid 4a-l
afforded the formation of thiazole, pyrazoline, and sydnone
heterocycles in single molecular framework 4a-l
(J = 2.32 Hz) and δ = 4.72 (J = 2.08 Hz). Ortho and meta
protons of p-tolyl ring came into resonance as two dou-
blets at δ = 6.92 (J = 8.68 Hz) and δ = 7.34 (J = 8.68 Hz),
while the aromatic protons attributed to the p-propynyloxy
phenyl ring appeared as two doublets at δ = 6.99
(J = 8.84 Hz) and δ = 7.56 (J = 8.08 Hz).
(Scheme 2). Though acetylene is better dienophile, the
thiosemicarbazide (S-N bi-nucleophile) is selectively
reacted with α, β unsaturated ketone (chalcone) in pres-
ence of a mild base. However, the newly synthesized moi-
ety can be utilized for the synthesis of various heterocycles,
for example, 1,2,3-triazole can be synthesized through
13
Similarly, C-NMR also avouches the formation of
the product by furnishing expected peaks. The presence
[25]
copper-catalyzed cycloaddition of organic azide.
More-
of methylene (CH ) and methine carbon (CH) of the
2
over, terminal acetylene can act as the best dienophile
towards the various nucleophiles.
pyrazoline ring appeared at δ 42.57 and δ 61.64 ppm. The
signals at δ 55.44, 55.71 ppm were observed for O-CH2
carbons, respectively. The appearance of a peak at
166.80 ppm indicated the presence of lactone ring in the
moiety (ester of sydnone). Furthermore, the appearance
[26,27]
The structures of newly synthesized thiazole hybrids
4
a-l were explicated using analytical and spectral data (IR,
1
13
H-NMR, C- NMR, CHN analysis and mass spectroscopy)
and they are in consistency with the proposed structure.
Thus, in the IR spectrum of thiazole hybrid 4k showed a
sharp band at 1732/cm due to sydnone C=O stretching,
whereas the absorption band due to ꢀC-H stretch was seen
at 3286/cm. The bands due to CꢀC stretching and C=N
stretching were seen at 2182 and 1606/cm.
+
of a molecular ion peak at m/z: 588.1 (M +1), also pro-
vided the evidence for the formation of products.
2.1 | Crystallography
1
In the H-NMR spectrum of 4k, the peaks due to
One of the synthesized compound 2d was recrystallized by
magnetically non-equivalent N-H disappeared while a
singlet at δ = 6.72 assigned to thiazole ring proton
appeared which confirmed the formation of product
slow evaporation method and resolved by direct methods
2
and refined by full-matrix least squares method on F using
[28,29]
SHELXS and SHELXL program.
culations were carried out using the program PLATON.
The molecular structure and packing diagrams were gener-
The geometrical cal-
[30]
(Figure S1). Methyl protons of p-tolyl ring attached to
sydnone appeared as a singlet at δ = 2.32, whereas two
triplets were seen at δ = 2.47 (J = 2.28 Hz) and δ = 2.53
[31]
ated with the help of MERCURY software . Crystallo-
graphic data for the compounds 2d have been deposited
with the Cambridge Crystallographic Data Centre as sup-
plementary publication number CCDC 1857199, copies of
this information may be obtained free of charge via www.
ccdc.cam.ac.uk/conts/retrieving.html (or from the CCDC,
12 Union Road, Cambridge CB2 1EZ, UK; fax:
+44-1223-336 033; e-mail: deposit@ccdc.cam.ac.uk).
(
J = 2.32 Hz) which is attributed to acetylenic protons.
The diastereotopic protons (Ha and Hb) and chiral
Hx) proton of pyrazoline ring appeared as three doublet
(
of doublets at δ = 3.24, δ = 3.78, and δ = 5.58 with cou-
pling constant Jab = 17.40 Hz, Jax = 11.92 Hz and
Jbx = 6.6 Hz integrating for one proton each. Aliphatic
-OCH2 protons appeared as a doublet at δ = 4.64

4
ASMA ET AL.
34
DPPH method in dimethyl sulfoxide (DMSO) solvent.
Butylated hydroxyanisole (BHA) was taken as standard”.
The in vitro antioxidant activity results are presented as a bar
diagram in Figure 4. All the experiments were performed in
triplicate, and the results are expressed as their mean values.
The precursor 5-(4-(prop-2-ynyloxy)phenyl)-3-(aryl)-4,-
5-dihydropyrazole-1-carbothioamide (2a-f) exhibited DPPH
scavenging activity varying from 90.7% to 77.18%, whereas
the product 2-(3-(aryl)-5-(4-(prop-2-ynyloxy)phenyl)-4,-
5-dihydropyrazol-1-yl)-4-(3-arylsydnone-4-yl)thiazole (4a-l)
FIGURE 2 Single crystal X-ray structure of compound 2d
showing the atomic numbering system. Displacement ellipsoids are
drawn at the 50% probability
showed DPPH scavenging activity varying from 74.7% to
4.6%. The standard BHA showed 88.4% inhibition
(Figure 4). Compound 5-(4-(prop-2-ynyloxy) phenyl)-3-(p-
fluorophenyl)-4,5-dihydropyrazole-1-carbothioamide 2c and
5-(4-(prop-2-ynyloxy) phenyl)-3-(p- anisyl)-4,5-dihydropyrazole-
1-carbothioamide (2b) showed radical scavenging activity
higher than the standard used, that is, 90.7% and 89.8%,
while 2-(3-(p-tolyl)-5-(4-[prop-2-ynyloxy] phenyl)-4,-
Synthesized compound 2d was crystallized in a mono-
clinic crystal system with P21/n space group (Figure 2). The
X-RD data of the compound 2d are given in (Table S1).
5-dihydropyrazol-1-yl)-4-(3-phenyl sydnone-4-yl)thiazole
2.2 | Hirshfeld surface
(4b) displayed the least DPPH scavenging activity of 4.6%.
Since the carbothioamide(thiole/thione tautomerization)
[35]
The intercontacts observed in the crystal structure of com-
pound 2d were quantized using the Hirshfeld surface analysis
and were presented in the following figures (Figure 3A-C).
The dark-red spots on the dnorm surface arise as a
result of the short interatomic contacts, that is, strong
hydrogen bonds, while the other intermolecular interac-
tions appeared as light-red spots (Figure 3B). The two-
dimensional (2D)-fingerprint plots were used to plot
intercontacts with respect to d and d (Figure 3A). The
has a better electron-donating capacity over thiazole deriva-
tives, it rapidly reduces the DPPH radical and showed bet-
ter DPPH inhibition compared to thiazole derivatives. The
overall study clearly manifests the importance of electron
donor molecules in the DPPH inhibition activity.
2.4 | Experimental
i
e
electrostatic potential is mapped on Hirshfeld surfaces
using Hartree-Fock (STO-3G basis set) theory over the
range of −0.30 a.u. to +0.30 a.u. (Figure 3B). The electro-
static potential surfaces were plotted (Figure 3C) with the
red region, which is a negative electrostatic potential
Thin layer chromatography (TLC) was used for checking
the progress and purity of the synthesized compounds
(ethyl acetate: hexane (1:9)/ (3:7) mobile phase). IR were
obtained in KBr discs (Shimadzu-8400 FTIR spectropho-
tometer). H-NMR and C-NMR spectra were recorded
on 400 MHz Bruker Avance spectrometer with DMSO-d6
(Deuterated Dimethyl sulfoxide) using TMS as an inter-
nal standard. CHN analysis was carried out on the
ElementarVario-EL III model analyzer. The X-ray diffrac-
tion of compound 2d obtained with Rigaku Saturn724+
diffractometer with graphite monochromated MoKa radi-
ation at 296 K. Melting point was observed by open glass
capillary method and were uncorrected.
1
13
(
hydrogen acceptors) and blue region, which is a positive
[32,33]
electrostatic potential (hydrogen donor)
.
The intercontacts were found to be Cl…H (10.9%), C…
H (18.2%), Cl…S (0.8%), Cl…N (1.0%), Cl…C (1.8%), H…H
(
(
31.6%), N…C (1.4%), N…H (4.2%), O…C (O.6%), S…H
12.2%), O…H (4.8%) (Figure 3A(i-xi)).
From the 2D Fingerprint plots, it was observed that the
major contributions are from H…H (31.6%), and C…H
18.2%) when compared to other intercontacts. Electrostatic
potential over the Hirshfeld surfaces is shown in Figure 3C.
(
2.5 | General procedure for the synthesis
of 5-(4-(prop-2-ynyloxy) phenyl)-3-aryl-4,5-
dihydropyrazole-1-carbothioamide (2a-f)
2.3 | Antioxidant studies
“
The newly synthesized dihydropyrazole-1-carbothioamide
2a-f) and thiazole derivatives (4a-l) were evaluated for
A mixture of 1-(p-substituted phenyl)-3-(4-(prop-2-ynyloxy)
phenyl)prop-2-en-1-one (1a-f) (1 mmol) and thiosemicarbazide
(0.7 g, 2 mmol) were taken in 50 mL of rb flask, 0.2 g of
potassium hydroxide in ethanol (10 mL) was added to it
(
their ability to bleach 2,2'-diphenyl-1-picrylhydrazyl (DPPH)
radical at the concentration of 100 μg/mL using modified

ASMA ET AL.
5
FIGURE 3
(
A) Fingerprint plots: The
outline of the full fingerprints
are shown in gray (a (i-xi)), d
i
is the closest internal distance
from a given point on the
e
Hirshfeld surface, and d is the
closest external contacts. (B):
The dnorm mapped on the
Hirshfeld surface for
(i) Cl…H–10.9 % (ii) C….H–18.2 % (iii) Cl…..S–0.8 % (iv) Cl….N–1.0 % (v) Cl….C–1.8 %
visualizing the intercontacts of
the compound 2d. (C):
Electrostatic potential mapped
on the Hirshfeld surface
(vi) H…..H–31.6 % (vii) N…..C–1.4 % (viii) N…..H–4.2 % (ix) O…..C–0.6 % (x) S….H–12.2 %
(
different orientation) with
0.30 au. The blue region
±
corresponds to positive
electrostatic potential and red
region to negative electrostatic
potential
(
a)
(xi) O….H–4.8 %
(xii) Fulll
(
b)
(
c)
ꢁ
1
and refluxed in an oil bath at 80 C for 6 hours. After the
reaction completion (monitored by TLC), the contents were
cooled to room temperature (Scheme 1). The solid product
obtained was filtered, washed with water, dried and rec-
rystallized from ethanol-dimethylformamide mixture.
(CꢀC), 1598 (C=N); H-NMR (DMSO-d , δ ppm): 2.35
6
(3H, s, CH ), 3.06 (dd, 1H, J = 3.4 Hz, J = 18 Hz,
3
bx
ba
Hb), 3.72 (t, 1H, J = 2.28 Hz, ꢀC-H), 3.76 (dd, 1H,
J
= 11.56 Hz, J = 17.88 Hz, Ha), 4.69 (d, 2H,
ax
ab
J = 2.28 Hz, OCH ), 5.87 (dd, 1H, J = 3.24 Hz,
2
xb
Jxa = 11.36 Hz, Hx), 6.87 (d, 2H, J = 8.68 Hz, ortho
protons of p-propynyloxy phenyl ring), 7.08 (d, 2H,
J = 8.64 Hz, meta protons of p-propynyloxy phenyl
ring), 7.21 (d, 2H, J = 8.08 Hz, ortho protons of p-
tolyl ring), 7.64 (bs, 1H, N-H), 7.70 (d, 2H,
J = 8.08 Hz, meta protons of p-tolyl ring), 7.89 (bs,
2
4
.6 | 5-(4-(Prop-2-ynyloxy)phenyl)-3-(p-tolyl)-
,5-dihydropyrazole-1-carbothioamide (2a)
ꢁ
mp 168-170 C; yield 74%; white powder; IR: νmax/cm
1
3
(
KBr): 3442 (N-H), 3285 (ꢀC-H), 3153 (Ar C-H), 2125
1H, N-H); C-NMR (DMSO-d , δ ppm): 21.31, 43.84,
6

6
ASMA ET AL.
2.8 | 5-(4-(Prop-2-ynyloxy) phenyl)-3-(p-
fluoro phenyl)-4,5-dihydropyrazole-
1-carbothioamide (2c)
ꢁ
−1
mp: 152-154 C; yield 73%; white powder; IR: νmax cm
(
(
(
KBr): 3426 (N-H), 3291 (ꢀC-H), 3113 (Ar C-H), 2127
1
CꢀC), 1583 (C=N); H-NMR (DMSO-d , δ ppm): 3.07
6
dd, 1H, J = 3.20 Hz, J = 17.84 Hz, Hb), 3.66 (t, 1H,
bx
ba
J = 2.28 Hz, ꢀC-H), 3.80 (dd, 1H, J = 11.58 Hz,
ax
J
ab
= 17.94 Hz, Ha), 4.68 (d, 2H, J = 2.32 Hz, OCH ), 5.78
2
(
dd, 1H, Jxb = 3.34 Hz, Jxa = 11.52 Hz, Hx), 6.82-7.59 (m,
5
7
5
1
1
H, Ar-H), 7.61 (bs, 1H, N-H), 7.67 to 7.73 (m, 3H, Ar-H),
13
.79 (bs, 1H, N-H); C-NMR (DMSO-d , δ ppm): 45.18,
6
8.42, 62.88, 76.32, 77.47, 77.12, 78.76, 78.63, 114.82,
14.97, 123.17, 125.74, 126.89, 135.96, 148.05, 157.18,
+
62.88, 176.64 (C=S); Mass spectrum, m/z: 354 (M +1);
Elemental Anal. Calcd (%) for C H FN OS: C, 64.58; H,
19
16
3
FIGURE 4 Antioxidant activity data of compound 2a-f and
4.54; N, 11.90. Found C, 64.57; H, 4.60; N, 11.86.
4
a-l
2
.9 | 5-(4-(Prop-2-ynyloxy) phenyl)-3-(p-
5
1
1
8.46, 67.51, 77.20, 77.42, 77.64, 78.20, 78.28, 114.30,
14.62, 123.82, 126.42, 127.74, 135.42, 144.53, 153.14,
chloro phenyl)-4,5-dihydropyrazole-
1-carbothioamide (2d)
58.98, 175.74 (C=S); Mass spectrum, m/z: 350
+
ꢁ
(
M +1); Elemental Anal. Calcd (%) for C H N OS: C,
mp: 148 C; yield 81%; yellowish brown powder; IR:
2
0
19
3
6
8.68; H, 5.50; N, 12.04. Found C, 68.74; H, 5.48;
νmax/cm (KBr): 3440 (N-H), 3265 (ꢀC-H), 3147 (Ar C-
1
N, 12.02.
H), 2123 (CꢀC), 1591 (C=N); H-NMR (DMSO-d , δ
6
ppm): 3.09 (dd, 1H, J = 3.32 Hz, J = 18 Hz, Hb), 3.72
bx
ba
(
J
t, 1H, J = 2.36 Hz, ꢀC-H), 3.84 (dd, 1H, J = 11.48 Hz,
ax
2
.7 | 5-(4-(Prop-2-ynyloxy) phenyl)-3-(p-
= 18 Hz, Ha), 4.56 (d, 2H, J = 2.36 Hz, OCH ), 5.73
ab 2
anisyl)-4,5-dihydropyrazole-
1
(dd, 1H, Jxb = 3.28 Hz, Jxa = 11.52 Hz, Hx), 6.65 (d, 2H,
J = 8.64 Hz, ortho protons of p-propynyloxy phenyl ring),
-carbothioamide (2b)
7.10 (d, 2H, J = 8.68 Hz, meta protons of p-propynyloxy
ꢁ
mp: 149-150 C; yield 79%; pale yellow powder; IR:
phenyl ring), 7.19 to 7.22 (m, 4H, J = 8.08 Hz, Ar-H), 7.52
13
νmax/cm (KBr): 3339 (N-H), 3269 (ꢀC-H), 3106 (Ar C-
(bs, 1H, N-H), 7.73 (bs, 1H, N-H); C-NMR (DMSO-d , δ
6
1
H), 2120 (CꢀC), 1574 (C=N); H-NMR (DMSO-d , δ
ppm): 43.90, 56.48, 62.62, 77.32, 77.47, 77.69, 78.28, 78.47,
114.49, 114.67, 123.87, 126.55, 127.82, 135.47, 144.61,
153.24, 159.06, 175.48 (C=S); Mass spectrum, m/z:
6
ppm): 3.09 (dd, 1H, J = 3.24 Hz, J = 18 Hz, Hb),
bx
ba
3
.69 (t, 1H, J = 2.32 Hz, ꢀC-H), 3.71 (dd, 1H,
+
+
J
= 11.52 Hz, Jab = 17.80 Hz, Ha), 3.78 (s, 3H, OCH ),
370 (M +1), 371.8 (M +3); Elemental Anal. Calcd (%)
ax
3
4
.52 (d, 2H, J = 2.32 Hz, OCH ), 5.76 (dd, 1H,
for C H ClN OS: C, 61.72; H, 4.38; N, 11.34. Found C,
2
19 16
3
Jxb = 3.20 Hz, Jxa = 11.32 Hz, Hx), 6.75 (d, 2H,
J = 8.84 Hz, ortho protons of p-propynyloxy phenyl
ring), 7.02 (d, 2H, J = 8.88 Hz, meta protons of
p-propynyloxy phenyl ring), 7.13 (d, 2H, J = 8.24 Hz,
ortho protons of p-anisyl ring), 7.59 (bs, 1H, N-H), 7.63
61.70; H, 4.41; N, 11.39.
2.10 | 5-(4-(Prop-2-ynyloxy) phenyl)-3-(p-
bromo phenyl)-4,5-dihydropyrazole-
1-carbothioamide (2e)
(
(
d, 2H, J = 8.08 Hz, meta protons of p-anisyl ring), 7.94
13
bs, 1H, N-H); C-NMR (DMSO-d , δ ppm): 45.55,
6
ꢁ
5
1
1
9.76, 62.13, 76.47, 77.55, 77.27, 79.86, 78.34, 115.42,
15.87, 124.60, 125.74, 126.83, 137.96, 147.54, 158.22,
mp: 182-184 C; yield 71%; white powder; IR: νmax/cm
(KBr): 3414 (N-H), 3276 (ꢀC-H), 3222 (Ar C-H), 2126
1
58.78, 175.34 (C=S); Mass spectrum, m/z: 365.8
(CꢀC), 1599 (C=N); H-NMR (DMSO-d , δ ppm): 3.09
6
+
(
M +1); Elemental Anal. Calcd (%) for C H N O S: C,
(dd, 1H, J = 3.4 Hz, J = 18 Hz, Hb), 3.32 (t, 1H,
2
0
19
3
2
bx
ba
6
5.72; H, 5.20; N, 11.52. Found C, 65.79; H, 5.24;
J = 2.24 Hz, ꢀC-H), 3.80 (dd, 1H, J = 11.52 Hz,
ax
N, 11.50.
J
= 17.96 Hz, Ha), 4.70 (d, 2H, J = 2.24 Hz, OCH ), 5.89
ab 2

ASMA ET AL.
7
(
dd, 1H, Jxb = 3.24 Hz, Jxa = 11.32 Hz, Hx), 6.88 (d, 2H,
J = 8.64 Hz, ortho protons of p-propynyloxy phenyl ring),
.07 (d, 2H, J = 8.64 Hz, meta protons of p-propynyloxy
2.13 | 2-(3-(p-Tolyl)-5-(4-[prop-2-ynyloxy]
phenyl)-4,5-dihydropyrazol-1-yl)-4-(3-(p-
tolyl) sydnone-4-yl)thiazole (4a)
7
phenyl ring), 7.58 (d, 2H, J = 8.48 Hz, ortho protons of p-
bromo phenyl ring), 7.60 (bs, 1H, N-H), 7.77 (d, 3H,
J = 8.56 Hz, meta protons of p-bromo phenyl ring and N-
ꢁ
−1
mp: 196-198 C; yield 74%; yellow powder; IR: νmax cm
(KBr): 3119 (ꢀC-H), 3278 (Ar C-H), 2120 (C ꢀ C), 1735
13
1
H), 8.00 (bs, 1H, N-H); C-NMR (DMSO-d , δ ppm):
(C=O), 1608 (C=N); H-NMR (DMSO-d , δ ppm): 2.37 (s,
6
6
4
1
1
4
4.11, 57.24, 63.32, 76.88, 77.34, 77.24, 78.28, 78.47,
13.12, 113.67, 122.92, 125.79, 126.82, 135.47, 144.41,
53.10, 158.58, 176.64 (C=S); Mass spectrum, m/z:
3H, CH ), 2.49(s, 3H, CH ), 2.51 (t, 1H, J = 2.4 Hz, ꢀC-
3
3
H), 3.11 (dd, 1H, J = 5.4 Hz, J = 17.44 Hz, Hb), 3.72
bx
ba
(dd, 1H, Jax = 11.96 Hz, Jab = 17.32 Hz, Ha), 4.66 (d, 2H,
J = 2.4 Hz, OCH ), 4.98 (dd, 1H, J = 5.44 Hz,
+
+
14 (M +1), 416 (M +3); Elemental Anal. Calcd (%) for
2
xb
C H BrN OS: C, 55.10; H, 3.90; N, 10.17 Found C,
Jxa = 11.92 Hz, Hx), 6.75 (d, 2H, J = 8.8 Hz, ortho protons
of p-tolyl ring), 7.30 (d, 2H, J = 8.4 Hz, meta protons of
p-tolyl ring), 7.57 (d, 2H, J = 8.16 Hz, Ar-H), 7.47 (s, 1H,
19
16
3
5
5.15; H, 3.90; N, 10.14.
13
thiazole-5H); C-NMR (DMSO-d , δ ppm): 21.37, 21.79,
6
2
3
4
.11 | 5-(4-(Prop-2-ynyloxy) phenyl)-
-((4-(prop-2-ynyloxy) phenyl)-
,5-dihydropyrazole-1-carbothioamide (2f)
43.72, 56.41, 63.65, 78.20, 78.46, 78.76, 78.84, 79.09,
103.81, 110.61, 122.17, 125.26, 127.12, 128.71, 128.18,
131.44, 131.78, 133.12, 135.29, 137.08, 152.27, 156.61,
+
1
64.21, 165.76; Mass spectrum, m/z: 547.8 (M +1); Ele-
ꢁ
mp: 215-217 C; yield 79%; white powder; IR: νmax/cm
mental Anal. Calcd (%) for C H N O S: C, 68.04; H,
31 25 5 3
(
(
(
KBr): 3399 (N-H), 3246 (ꢀC-H), 3209 (Ar C-H), 2124
4.68; N, 12.80 Found C, 67.99; H, 4.60; N, 12.88.
1
CꢀC), 1607 (C=N); H-NMR (DMSO-d , δ ppm): 3.08
6
dd, 1H, J = 3.32 Hz, J = 17.84 Hz, Hb), 3.21 (t, 1H,
bx
ba
J = 2.36 Hz, ꢀC-H), 3.27 (t, 1H, J = 2.32 Hz, ꢀC-H), 3.77
2.14 | 2-(3-(p-Tolyl)-5-(4-(prop-2-ynyloxy)
phenyl)-4,5-dihydropyrazol-1-yl)-
4-(3-(phenyl) sydnone-4-yl)thiazole (4b)
(
dd, 1H, J = 11.36 Hz, J = 17.8 Hz, Ha), 4.69 (d, 2H,
ax
ab
J = 2.36 Hz, OCH ), 4.80 (d, 2H, J = 2.40 Hz, OCH ),
2
2
5
2
.87 (dd, 1H, Jxb = 3.08 Hz, Jxa = 11.16 Hz, Hx), 6.87 (d,
H, J = 11.32 Hz, ortho protons of p-propynyloxy phenyl
ꢁ
mp: 170 tc172 C; yield 68%; orange powder; IR: νmax/cm
ring), 7.01 (d, 2H, J = 8.88 Hz, ortho protons of p-
propynyloxy phenyl ring), 7.08 (d, 2H, J = 8.72 Hz, meta
protons of p-propynyloxy phenyl ring), 7.58 (bs, 1H, N-H),
(KBr): 3103 (ꢀC-H), 3283 (Ar C-H), 2120 (CꢀC), 1731
1
(C=O), 1598 (C=N); H-NMR (DMSO-d , δ ppm): 2.35 (s,
6
3H, CH ), 2.52 (t, 1H, J = 2.36 Hz, ꢀC-H), 3.14 (dd, 1H,
3
7
.77 (dd, 2H, J = 11.32 Hz, meta protons of p-propynyloxy
J = 5.56 Hz, J = 17.62 Hz, Hb), 3.71 (dd, 1H,
bx ba
13
phenyl ring), 7.83 (bs, 1H, N-H); C-NMR (DMSO-d , δ
Jax = 11.88 Hz, Jab = 17.56 Hz, Ha), 4.62 (d, 2H,
J = 2.4 Hz, OCH ), 4.90 (dd, 1H, J = 5.40 Hz,
6
ppm): 42.46, 55.27, 55.48, 62.08, 77.18, 77.56, 78.15 to
2
xb
7
1
8.19, 78.52 to 78.67, 78.72 to 78.85, 114.49, 114.79, 123.88,
Jxa = 11.80 Hz, Hx), 6.69 (d, 2H, J = 8.8 Hz, ortho protons
of p-tolyl ring), 6.78 to 7.19 (m, 7H, Ar-H), 7.22 (d, 2H,
J = 8.8 Hz, meta protons of p-tolyl ring), 7.39 (d, 2H,
26.45, 128.43, 135.49, 154.55, 156.14, 158.99, 175.75
+
(C=S); Mass spectrum, m/z: 390 (M +1); Elemental Anal.
1
3
Calcd (%) for C H N O S: C, 67.88; H, 4.84; N, 10.88
J = 8.12 Hz, Ar-H), 7.48 (s, 1H, thiazole-5H); C-NMR
22
19 3 2
Found C, 67.83; H, 4.92; N, 10.79.
(DMSO-d , δ ppm): 15.28, 44.71, 56.21, 62.39, 77.97,
6
78.83, 79.69, 79.91, 80.10, 105.53, 107.68, 113.71, 124.85,
127.23, 127.61, 128.45, 128.97, 130.10, 131.69, 131.90,
2
.12 | General procedure for the
133.54, 134.67, 137.14, 154.28, 163.12, 166.22; Mass spec-
trum, m/z: 534 (M +1); Elemental Anal. Calcd (%) for
+
synthesis of 2-(3-(aryl)-5-(4-(prop-
2
4
-ynyloxy) phenyl)-4,5-dihydropyrazol-1-yl)-
-(3-arylsydnone-4-yl)thiazole (4a-l)
C H N O S: C, 67.62; H, 4.38; N, 13.14 Found C,
30
23 5 3
67.53; H, 4.34; N, 13.19.
A
mixture of 5-(4-(prop-2-ynyloxy) phenyl)-3-aryl-4,-
5
4
-dihydropyrazole-1-carbothioamide (2a-f) (1 mmol) and
-bromoacetyl-3-(aryl) sydnone (3a-b) (1 mmol) in ethanol
2.15 | 2-(3-(p-Anisyl)-5-(4-(prop-
2-ynyloxy)phenyl)-4,5-dihydropyrazol-1-yl)-
4-(3-(p-tolyl) sydnone-4-yl)thiazole (4c)
(10 mL) was taken in a round-bottomed flask and stirred at
room temperature for 10 to 12 hours (Scheme. 2). The solid
mass obtained was filtered, washed with ethanol, dried and
recrystallized from ethanol.
ꢁ
mp: 188 to 190 C; yield 77%; yellow powder; IR:
νmax/cm (KBr): 3288 (ꢀC-H), 3128 (Ar C-H), 2159

8
ASMA ET AL.
1
(
CꢀC), 1735 (C=O), 1609 (C=N); H-NMR (DMSO-d , δ
ppm): 2.32 (s, 3H, CH ), 2.48 (t, 1H, J = 2.36 Hz, ꢀC-H),
6
3
ppm): 2.49 (s, 3H, CH ), 2.51 (t, 1H, J = 2.36 Hz, ꢀC-H),
3.25 (dd, 1H, J = 6.72 Hz, J = 17.44 Hz, Hb), 3.80 (dd,
3
bx
ba
3
1
.10 (dd, 1H, J = 5.44 Hz, J = 17.36 Hz, Hb), 3.71 (dd,
1H, Jax = 12 Hz, Jab = 17.44 Hz, Ha), 4.65 (d, 2H,
J = 2.4 Hz, OCH ), 5.60 (dd, 1H, J = 6.68 Hz,
bx
ba
H, Jax = 11.88 Hz, Jab = 17.32 Hz, Ha), 3.78 (s, 3H,
2
xb
OCH ), 4.66 (d, 2H, J = 2.36 Hz, OCH ), 4.96 (dd, 1H,
Jxa = 11.88 Hz, Hx), 6.74 (s, 1H, thiazole-5H), 6.92 to 7.75
3
2
13
Jxb = 5.36 Hz, Jxa = 11.80 Hz, Hx), 6.75 (d, 2H, J =
.8 Hz, ortho protons of p-tolyl ring), 6.80 (d, 2H,
(m, 12H, Ar-H); C-NMR (DMSO-d , δ ppm): 15.28,
6
8
43.32, 55.67, 62.90, 77.81, 78.60, 79.08, 79.44, 79.92,
104.22, 107.41, 114.32, 124.12, 126.48, 127.40, 128.79,
128.96, 132.40, 132.80, 133.13, 133.42, 137.25, 152.33.
J = 8.8 Hz, meta protons of p-tolyl ring), 6.89 (d, 2H,
J = 8.88 Hz, ortho protons of p-propynyloxy phenyl ring),
+
7
7
.17 (d, 2H, J = 8.2 Hz, ortho protons of p-anisyl ring),
.30 (d, 2H, J = 8.36 Hz, meta protons of p-anisyl ring), 7.46
164.54, 165.28, 166.45; Mass spectrum, m/z: 552 (M +1);
Elemental Anal. Calcd (%) for C H FN O S: C,
30
22
5 3
(
s, 1H, thiazole-5H), 7.61 (d, 2H, J = 8.84 Hz, meta protons
65.38; H, 4.08; N, 12.82 Found C, 65.32; H, 4.02; N, 12.70.
1
3
of p-propynyloxy phenyl ring); C-NMR (DMSO-d , δ
6
ppm): 21.28, 55.45, 56.54, 63.12, 77.28, 77.80, 78.13,
7
1
1
8.26, 78.64, 104.54, 104.91, 110.17, 110.64, 126.32,
27.88, 130.43, 130.91, 134.47, 134.82, 135.25, 135.70,
2.18 | 2-(3-(p-Fluorophenyl)-5-(4-(prop-
2-ynyloxy)phenyl)-4,5-dihydropyrazol-1-yl)-
4-(3-(phenyl) sydnone-4-yl)thiazole (4f)
36.42, 152.28, 159.67, 161.38, 162.64, 165.33; Mass spec-
+
trum, m/z: 564.15 (M +1); Elemental Anal. Calcd (%)
for C H N O S: C, 66.10; H, 4.49; N, 12.52 Found C,
ꢁ
mp: 189 to 191 C; yield 74%; yellow powder; IR:
31
25
5 4
6
6.06; H, 4.47; N, 12.43.
νmax/cm (KBr): 3299 (ꢀC-H), 2965 (Ar C-H), 2127
1
(
CꢀC), 1735 (C=O), 1603 (C=N); H-NMR (DMSO-d , δ
6
ppm): 2.45 (t, 1H, J = 2.36 Hz, ꢀC-H), 3.29 (dd, 1H,
ba
2
2
4
.16 | 2-(3-(p-Anisyl)-5-(4-(prop-
-ynyloxy)phenyl)-4,5-dihydropyrazol-1-yl)-
-(3-(phenyl) sydnone-4-yl)thiazole (4d)
J
bx
= 6.68 Hz, J = 17.40 Hz, Hb), 3.75 (dd, 1H,
Jax = 12 Hz, Jab = 17.44 Hz, Ha), 4.64 (d, 2H, J = 2.8 Hz,
OCH ), 5.57 (dd, 1H, J = 6.64 Hz, Jxa = 11.96 Hz, Hx),
2
xb
6
.76 (s, 1H, thiazole-5H), 6.88-7.26 (m, 8H, Ar-H), 7.31 to
ꢁ
13
mp: 205 to 207 C; yield 82%; yellow powder; IR:
7.69 (m, 5H, Ar-H); C-NMR (DMSO-d , δ ppm): 43.12,
6
νmax/cm (KBr): 3279 (ꢀC-H), 3198 (Ar C-H), 2142
55.64, 62.98, 77.82, 78.64, 79.02, 79.41, 79.89, 104.94,
108.30, 114.64, 124.04, 126.42, 127.37, 128.31, 128.91,
131.43, 131.86, 133.39, 135.21, 136.27, 152.39, 164.55,
1
(
CꢀC), 1737 (C=O), 1598 (C=N); H-NMR (DMSO-d , δ
6
ppm): 2.53 (t, 1H, J = 2.36 Hz, ꢀC-H), 3.16 (dd, 1H,
+
J
= 5.56 Hz, J = 17.32 Hz, Hb), 3.69 (dd, 1H,
165.14, 166.70; Mass spectrum, m/z: 538 (M +1); Ele-
bx
ba
Jax = 11.80 Hz, Jab = 17.32 Hz, Ha), 3.73 (s, 3H, OCH3),
.58 (d, 2H, J = 2.32 Hz, OCH ), 4.91 (dd, 1H,
mental Anal. Calcd (%) for C H FN O S: C, 64.84; H,
3.82; N, 13.07 Found C, 64.79; H, 3.75; N, 13.03.
29
20
5 3
4
2
Jxb = 5.40 Hz, Jxa = 11.88 Hz, Hx), 6.69 (d, 2H,
J = 8.84 Hz, ortho protons of p-tolyl ring), 6.76 (d, 2H,
J = 8.88 Hz, meta protons of p-tolyl ring), 6.83 to 7.57 (d,
2.19 | 2-(3-(p-Chloro phenyl)-5-(4-(prop-
2-ynyloxy) phenyl)-4,5-dihydropyrazol-1-yl)-
4-(3-(p-tolyl) sydnone-4-yl)thiazole (4 g)
13
9
H, Ar-H), 7.59 (s, 1H, thiazole-5H); C-NMR (DMSO-
d6, δ ppm): 43.81, 55.51, 56.60, 63.30, 77.86, 77.98, 78.22,
7
1
1
8.44, 79.12, 105.17, 105.62, 110.12, 110.86, 125.27,
27.80, 130.42, 130.89, 133.44, 133.44, 133.76, 135.17,
ꢁ
mp: 154 to 156 C; yield 80%; orange powder; IR:
35.08, 136.17, 152.18, 159.62, 161.62, 162.66, 165.18;
νmax/cm (KBr): 3298 (ꢀC-H), 2956 (Ar C-H), 2131
+
1
Mass spectrum, m/z: 549.75 (M +1); Elemental Anal.
Calcd (%) for C H N O S: C, 65.62; H, 4.28; N, 12.82
Found C, 65.56; H, 4.22; N, 12.74.
(CꢀC), 1736 (C=O), 1594 (C=N); H-NMR (DMSO-d , δ
6
ppm): 2.34 (s, 3H, CH ), 2.49 (t, 1H, J = 2.36 Hz, ꢀC-H),
30
23
5
4
3
3.06 (dd, 1H, J = 5.44 Hz, J = 17.92 Hz, Hb), 3.75 (dd,
bx
ba
1H, Jax = 11.96 Hz, Jab = 18 Hz, Ha), 4.78 (d, 2H,
J = 2.32 Hz, OCH ), 4.99 (dd, 1H, J = 5.36 Hz,
2
xb
2
2
4
.17 | 2-(3-(p-Fluorophenyl)-5-(4-(prop-
-ynyloxy)phenyl)-4,5-dihydropyrazol-1-yl)-
-(3-(p-tolyl) sydnone-4-yl)thiazole (4e)
Jxa = 11.96 Hz, Hx), 6.63 (d, 2H, J = 8.68 Hz, ortho pro-
tons of p-chloro phenyl ring), 6.73 (s, 1H, thiazole-5H),
6.79 (d, 2H, J = 8.56 Hz, meta protons of p-propynyloxy
phenyl ring), 7.21 (d, 2H, J = 8.76 Hz, ortho protons of p-
tolyl ring) 7.28 (d, 2H, J = 8.28 Hz, meta protons of p-
chloro phenyl ring), 7.42 (d, 2H, J = 8.8 Hz, meta protons
of p-tolyl ring), 7.51 (dd, 2H, J = 7.6 Hz, ortho protons of
ꢁ
mp: 208 to 210 C; yield 77%; yellow powder; IR:
νmax/cm (KBr): 3286 (ꢀC-H), 2974 (Ar C-H), 2136
1
(CꢀC), 1733 (C=O), 1589 (C=N); H-NMR (DMSO-d , δ
6

ASMA ET AL.
9
1
3
p-propynyloxy phenyl ring); C-NMR (DMSO-d , δ ppm):
protons of p-tolyl ring), 7.55 (d, 2H, J = 8.52 Hz, meta
protons of p-tolyl ring), 7.66 (d, 2H, J = 8.12 Hz, meta
6
4
1
1
1
5
4.15, 56.17, 63.22, 77.94, 78.62, 79.33, 79.81, 80.15,
05.63, 108.14, 113.80, 124.89, 127.14, 127.39, 128.44,
28.98, 129.12, 132.11, 131.89, 133.24, 135.17, 137.04,
53.11, 162.60, 165.40; Mass spectrum, m/z: 568 (M +1),
70 (M +3); Elemental Anal. Calcd (%) for
1
3
protons of p-propynyloxy phenyl ring);
C-NMR
(DMSO-d , δ ppm): 15.46, 41.45, 54.79, 62.36, 77.61,
6
+
77.48, 78.32, 78.69, 79.28, 105.80, 107.52, 112.60, 124.67,
124.89, 126.18, 127.94, 128.88, 131.63, 132.12, 132.79,
134.86, 135.42, 153.34, 155.72, 165.33, 166.41; Mass spec-
+
C H ClN O S: C, 63.48; H, 3.92; N, 12.30 Found C,
30
22
5 3
+
6
3.43; H, 3.90; N, 12.33.
trum, m/z: 612.6 (M +1); Elemental Anal. Calcd (%) for
C H BrN O S: C, 58.69; H, 3.99; N, 11.40 Found C,
30
24
5 3
58.64; H, 3.94; N, 11.40.
2
2
4
.20 | 2-(3-(p-Chlorophenyl)-5-(4-(prop-
-ynyloxy)phenyl)-4,5-dihydropyrazol-1-yl)-
-(3-(phenyl) sydnone-4-yl)thiazole
2.22 | 2-(3-(p-Bromophenyl)-5-(4-(prop-
2-ynyloxy)phenyl)-4,5-dihydropyrazol-1-yl)-
(4 hours)
4
-(3-(phenyl) sydnone-4-yl)thiazole (4j)
ꢁ
mp: 169 C; yield 79%; yellow powder; IR: νmax/cm
ꢁ
(
(
KBr): 3277 (ꢀC-H), 2987 (Ar C-H), 2359(CꢀC), 1733
mp: 216 to 218 C; yield 86%; orange powder; IR:
1
C=O), 1587 (C=N); H-NMR (DMSO-d , δ ppm): 2.53 (t,
νmax/cm (KBr): 3265 (ꢀC-H), 2988 (Ar C-H), 2117
6
1
1
H, J = 2.36 Hz, ꢀC-H), 3.18 (dd, 1H, J = 5.44 Hz,
(CꢀC), 1726 (C=O),1589 (C=N); H-NMR (DMSO-d , δ
bx
6
J
= 17.96 Hz, Hb), 3.86 (dd, 1H, J
= 12 Hz,
ax
ppm): 2.51 (t, 1H, J = 2.36 Hz, ꢀC-H), 3.17 (dd, 1H,
ba
Jab = 17.96 Hz, Ha), 4.71 (d, 2H, J = 2.36 Hz, OCH ), 5.01
J
= 5.36 Hz, J = 18.04 Hz, Hb), 3.85 (dd, 1H,
2
bx ba
(
dd, 1H, Jxb = 5.28 Hz, Jxa = 11.84 Hz, Hx), 5.61 (s, 1H,
Jax = 12.04 Hz, Jab = 18.08 Hz, Ha), 4.73 (d, 2H,
J = 2.36 Hz, OCH ), 4.94 (dd, 1H, J = 5.2 Hz,
thiazole-5H), 6.69 (d, 2H, J = 8.72 Hz, ortho protons of p-
chloro phenyl ring), 6.80 (d, 2H, J = 8.76 Hz, meta pro-
tons of p-propynyloxy phenyl ring), 7.33 (d, 2H,
J = 8.28 Hz, meta protons of p-chloro phenyl ring), 7.42
to 7.46 (m, 5H, Ar-H), 7.71 (dd, 2H, J = 6.8 Hz, ortho pro-
tons of p-propynyloxy phenyl ring); C-NMR (DMSO-d6,
δ ppm): 43.97, 57.01, 61.23, 79.36, 79.62, 79.79, 80.07,
8
1
1
2
xb
Jxa = 11.88 Hz, Hx), 6.65 (d, 2H, J = 8.72 Hz, ortho pro-
tons of p-bromo phenyl ring), 6.80 (d, 2H, J = 8.72 Hz,
meta protons of p-bromo phenyl ring), 7.43 (s, 1H,
1
3
thiazole-5H), 7.57 to 7.71 (m, 9H, Ar-H); C-NMR
13
(DMSO-d , δ ppm): 42.77, 55.29, 62.90, 77.81, 78.48,
6
78.81, 78.89, 79.14, 104.90, 108.22, 114.54, 123.41, 125.56,
127.14, 128.13, 128.78, 131.43, 131.62, 133.40, 135.02,
136.32, 152.24, 156.42, 164.13, 165.90; Mass spectrum,
2.71, 103.21, 105.79, 113.29, 126.01, 126.97, 127.33,
28.25, 128.77, 129.21, 130.09, 130.66, 133.54, 134.93,
37.21, 154.06, 163.17, 165.56; Mass spectrum, m/z: 553.8
+
m/z: 598 (M +1); Elemental Anal. Calcd (%) for
+
+
(
M +1), 556 (M +3); Elemental Anal. Calcd (%) for
C H BrN O S: C, 58.15; H, 3.42; N, 11.71 Found C,
29
20
5 3
C H ClN O S: C, 62.89; H, 3.60; N, 12.62 Found C,
58.20; H, 3.37; N, 11.70.
29
20
5 3
6
2.87; H, 3.64; N, 12.65.
2
.23 | 2-(3-(4-(Prop-2-ynyloxy) phenyl)-
2
2
4
.21 | 2-(3-(p-Bromophenyl)-5-(4-(prop-
-ynyloxy)phenyl)-4,5-dihydropyrazol-1-yl)-
-(3-(p-tolyl) sydnone-4-yl)thiazole (4i)
5-(4-(prop-2-ynyloxy) phenyl)-4,5-dihydro
pyrazol-1-yl)-4-(3-(p-tolyl) sydnone-4-yl)
thiazole (4 k)
ꢁ
ꢁ
mp: 179 to 181 C; yield 75%; yellow powder; IR:
mp: 188 C; yield 85%; yellow powder; IR: νmax/cm
νmax/cm (KBr): 3290 (ꢀC-H), 3136 (Ar C-H), 2159
(KBr): 3286 (ꢀC-H), 2987 (Ar C-H), 2182 (CꢀC), 1732
1
1
(
CꢀC), 1736 (C=O),1610 (C=N); H-NMR (DMSO-d , δ
(C=O), 1606 (C=N); H-NMR (DMSO-d , δ ppm): 2.32 (s,
6
6
ppm): 2.42 (s, 3H, CH ), 2.51 (t, 1H, J = 2.36 Hz, ꢀC-H),
3H, CH ), 2.47 (t, 1H, J = 2.28 Hz, ꢀC-H), 2.53 (t, 1H,
3
3
3
1
.29 (dd, 1H, J = 6.68 Hz, J = 17.48 Hz, Hb), 3.84 (dd,
H, Jax = 11.92 Hz, Jab = 17.44 Hz, Ha), 4.68 (d, 2H,
J = 2.32 Hz, ꢀC-H), 3.24 (dd, 1H, J = 6.6 Hz,
bx
bx
ba
J = 17.4 Hz, Hb), 3.78 (dd, 1H, J = 11.92 Hz,
ba ax
J = 2.36 Hz, OCH ), 5.57 (dd, 1H, J = 6.64 Hz,
Jab = 17.4 Hz, Ha), 4.64 (d, 2H, J = 2.32 Hz, OCH ), 4.72
2
xb
2
Jxa = 11.88 Hz, Hx), 6.81 (s, 1H, thiazole-5H), 6.96 (d, 2H,
J = 8.72 Hz, ortho protons of p-bromo phenyl ring), 7.24
(d, 2H, J = 2.08 Hz, OCH ), 5.58 (dd, 1H, J = 6.56 Hz,
2
xb
Jxa = 11.76 Hz, Hx), 6.72 (s, 1H, thiazole-5H), 6.92 (d, 2H,
J = 8.68 Hz, ortho protons of p-tolyl ring), 6.99 (d, 2H,
J = 8.84 Hz, ortho protons of p-propynyloxy phenyl ring),
7.10 (d, 2H, J = 8.00 Hz, ortho protons of p-propynyloxy
(
d, 2H, J = 7.36 Hz, ortho protons of p-propynyloxy phe-
nyl ring), 7.36 (d, 2H, J = 8.68 Hz, meta protons of p-
bromo phenyl ring), 7.44 (d, 2H, J = 8.52 Hz, ortho

10
ASMA ET AL.
phenyl ring), 7.34 (d, 2H, J = 8.68 Hz, meta protons of p-
tolyl ring), 7.56 (d, 2H, J = 8.08 Hz, meta protons of p-
propynyloxy phenyl ring), 7.69 (d, 2H, J = 8.76 Hz, meta
the ability of molecule to undergo amine/imine
tautomerization.
Soon after the cyclization of carbothioamide into thia-
zole derivatives, the DPPH activity was reduced. The less
pronounced radical inhibition activity of thiazole deriva-
tives (4a-l) majorly attributed to the lack of electron/ pro-
ton donor capacity in the synthesized molecules. Further
with the help of Hirshfeld surface computational method
short contacts in the crystal structure are quantified and
visualized (2D fingerprint plot) and major intercontacts
present in compound 2d are H…H (31.6%), C…H (18.2%).
13
protons of p-propynyloxy phenyl ring);
C-NMR
(
DMSO-d , δ ppm): 21.26, 42.57, 55.44, 55.71, 61.64,
6
7
1
1
1
7.28, 77.66, 78.32 to 78.41, 78.55 to 78.69, 78.70 to 78.83,
14.40, 114.72, 123.89, 126.47, 127.18, 128.37, 128.64,
35.62, 135.78, 136.51, 139.40, 140.81, 152.62, 158.37,
60.26, 162.44, 166.80; Mass spectrum, m/z: 588.1
+
(M +1); Elemental Anal. Calcd (%) for C H N O S: C,
33
25 5 4
6
7.49; H, 4.32; N, 12.02 Found C, 67.45; H, 4.29; N, 11.92.
ACKNOWLEDGMENTS
2
5
.24 | 2-(3-(4-(Prop-2-ynyloxy)phenyl)-
-(4-(prop-2-ynyloxy)phenyl)-4,5-dihydro
The authors are thankful to SAIF Punjab University,
PURSE laboratory Mangalore University for providing
the facility for spectral analysis. Asma is thankful to
UGC, New Delhi for Maulana Azad National Senior
Research Fellowship (MANF).
pyrazol -1-yl)-4-(3-(phenyl) sydnone-4-yl)
thiazole (4l)
ꢁ
mp: 155 to 157 C; yield 79%; yellow powder; IR:
νmax/cm (KBr): 3312 (ꢀC-H), 3290 (Ar C-H), 2136
ORCID
1
(
CꢀC), 1731 (C=O) and 1608 (C=N); H-NMR (DMSO-
Balakrishna Kalluraya https://orcid.org/0000-0003-
d , δ ppm): 3.13 (dd, 1H, J = 5.28 Hz, J = 17.84 Hz,
6
bx
ba
0442-7178
Hb),δ 3.29 (t, 1H, J = 2.4 Hz, ꢀC-H), 3.31 (t, 1H,
J = 2.28 Hz, ꢀC-H), 3.81 (dd, 1H, J = 11.88 Hz,
ax
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SUPPORTING INFORMATION
Additional supporting information may be found online
in the Supporting Information section at the end of this
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