A simple and environmentally benign synthesis of novel spiro[indoline-3,5′-pyrano[2,3-d]pyrimidine] derivatives in water

Article abstract of DOI:10.1007/s00706-019-2356-6

Abstract: A green, convenient, and efficient one-pot synthesis of a new class of spiro[indolinepyranopyrimidine] derivatives was achieved in good yields by the multi-component reaction of N-alkyl-1-(methylthio)-2-nitroethenamine derived from the addition

Full text of DOI:10.1007/s00706-019-2356-6

Monatshefte für Chemie - Chemical Monthly
https://doi.org/10.1007/s00706-019-2356-6
ORIGINAL PAPER
A simple and environmentally benign synthesis of novel spiro[indolin
e‑3,5′‑pyrano[2,3‑d]pyrimidine] derivatives in water
Sakineh Ghadiri1 · Mohammad Bayat1 · Fahimeh Sadat Hosseini1
Received: 20 June 2018 / Accepted: 8 January 2019
© Springer-Verlag GmbH Austria, part of Springer Nature 2019
Abstract
A green, convenient, and efcient one-pot synthesis of a new class of spiro[indolinepyranopyrimidine] derivatives was
achieved in good yields by the multi-component reaction of N-alkyl-1-(methylthio)-2-nitroethenamine derived from the
addition of various amines to nitroketene dithioacetal with isatin and barbituric acid derivatives in water at refux conditions.
Notably, the present method ofers desirable advantages including good yields, use of water as green solvent, absence of
catalyst, simple workup procedure, and easy purifcation process with no chromatographic technique.
Graphical abstract
R2
N
O
X
O
O
R3
X
R3
O
R3
O
O2N
H
NHR1
SCH3
O2N
H
R1
N
H2O, reflux
7-10 h
N
N
O
+
+
N
O
N
N
R2
R3
X = O, S
Use of water as a green solvent
Absence of catalyst
R1 = CH3, CH2CH3, CH(CH3)2, CH2Ph
R2 = H, CH3, CH2Ph
Potentially bioactive product
9 Examples up to 81%
R
3 = H, CH3
Keywords Spiro[indolinepyranopyrimidine] · Amines · Nitroketene dithioacetal · Isatin · Barbituric acid
Introduction
3-carbon atom in the formation of spiroindole derivatives
(Fig. 1) signifcantly improves biological properties [10].
Spiroindoles have generated considerable synthetic inter-
est due to their occurrence in diverse natural products and
notable biological activities [11–21].
Indole derivatives have been a topic of substantial research
interest and continue to be one of the most active areas of
heterocyclic chemistry. They exhibit a wide range of bio-
logical activities [1–4] such as antibacterial, antimicrobial,
antiviral, antifungal, antihypertensive, anti-infammatory
[5], antitumor [6], anticancer, anti-HIV, antioxidant [7], anti-
malarial, anticonvulsant [8], and anti-alzheimer [9] proper-
ties. In addition, it was reported that sharing of the indole
Pyranopyrimidine derivatives are very important and
valuable compounds, due to their potential importance in
the medicine and biological felds [22]. They have diverse
pharmacological properties such as antimalarial, antibacte-
rial [23], antifungal, antiviral, antitumor [23, 24], antibron-
chitic [25, 26], anti-AIDS [27], antipyretic [28], anti-infam-
matory [29], and antihypertensive [30] evaluation activities.
Considering the above reports, the development of new and
simple synthetic methods for the efcient preparation of the
spiroindoles containing pyranopyrimidine fragment could
potentially lead to a series of structurally and biologically
interesting heterocycles.
Electronic supplementary material The online version of this
article (https://doi.org/10.1007/s00706-019-2356-6) contains
supplementary material, which is available to authorized users.
* Mohammad Bayat
bayat_mo@yahoo.com; m.bayat@sci.ikiu.ac.ir
During the past decades, specific strategies have
been reported for the synthesis of spiroindole-annulated
1
Department of Chemistry, Faculty of Science, Imam
Khomeini International University, Qazvin, Iran
Vol.:(0123456789)
1 3

S. Ghadiri et al.
Fig. 1 Spiroindole derivatives
linked at position three of the
indole
spiro[indolinepyranopyrazoles] by reacting isatins, malo-
nonitrile, and 3-methyl-1H-pyrazol-5(4H)-ones in water
at room temperature (Scheme 1, entry c) [11]. Herein we
report an environmentally benign synthesis of a new class
of spiro[indolinepyranopyrimidine] derivatives via a cata-
lyst free, one-pot, multi-component condensation reaction of
various amines, nitroketene dithioacetal, isatin derivatives,
and barbituric acids in refuxing water (Scheme 1, entry d).
O
N
H
heterocycles. In 2010, Bazgir et al. reported an efcient,
one-pot synthesis of spiro[chromenopyrimidineindoline]
from cyclohexane-1,3-diones, isatins, and barbituric acids in
refuxing water in the presence of p-TSA for 10 h (Scheme 1,
entry a) [10, 13]. In 2015, Esmaeili et al. developed a rapid
and convenient protocol for the synthesis of novel spiro-
oxindole derivatives in excellent yields by the three-com-
ponent reaction of malononitrile, isatin, and 2,3-dihydro-
5H-[1,3]thiazolo[3,2-a]pyrimidine-5,7(6H)-dione in the
presence of diisopropylethylamine (Scheme 1, entry b) [14].
In 2018, Deka et al. described a simple and cost-efective,
micelle-catalyzed one-pot strategy for the synthesis of
Results and discussion
In this paper, we would like to report an easy
and efficient procedure for synthesizing novel
spiro[indolinepyranopyrimidine] derivatives. The products
were obtained from the addition of various amines 1 to
nitroketene dithioacetal 2 with isatin 3 and barbituric acid
derivatives 4 in water as a green solvent at refux conditions
(Scheme 2).
Scheme 1
(a) Bazgir’s work
HN
O
O
O
O
O
re ux
fl
H
2O /
HN
NH
O
NH
-
T A
S
p
N
O
O
O
O
H
N
H
O
O
(b) Esmaeili’s work
H2N
NC
O
N
S
O
R1
O
N
O
N
S
R1
CN
CN
DIEA
EtOH, reflux
O
O
N
O
N
N
R2
R2
(c) Deka’s work
HN
O
H3C
H3C
O
CN
CN
CN
NH2
SDS
O
N
N
O
N
H
H2O, r.t.
N
N
O
H
H
(d) This work
R2
N
O
X
O2N HN R1
H2O, reflux
O
O2N
O
R3
R3
O
R3
O
N
N
N
N
R2
SCH3
H
O
HN
O
N
R3
X
R1
1 3

A simple and environmentally benign synthesis of novel…
Scheme 2
O2N
SCH3
SCH3
R2
R1NH2
N
H
O
O
R3
X
1
2
+
H2O, reflux
X = O, S
O2N
H
N
O
X
N
O
N
R3
O
R3
N
R1
R3
N
N
R2
5
O
O
R1 = CH3, CH2CH3, CH(CH3)2, CH2Ph
R2 = H, CH3, CH2Ph
3
4
R3 = H, CH3
Table 1 Optimization of reaction conditions for 5c
Several solvents in the presence and absence of catalyst
were examined to develop standard reaction conditions and
the results are summarized in Table 1. Experimental results
showed that the reaction proceeded very cleanly with good
yield when the EtOH and water were used as solvent at
refux conditions without any catalyst (Table 1, entries 2
and 6). The yield of product was low, when the water was
used as solvent at 60 °C and room temperature (Table 1,
entries 7 and 8). Also the yield of product was low, when the
reaction was performed in the presence of piperidine or Et3N
as catalyst in EtOH (Table 1, entries 3 and 4). The reaction
did not proceed well, when the CH3CN and DMF were used
as solvent (Table 1, entries 9 and 11). Also the reaction did
not work in CHCl3, so a lot of spots were observed on TLC
(Table 1, entry 10).
Entry
Conditions
Catalyst
Time/h
Yield/%
1
2
3
4
5
6
7
8
9
10
11
EtOH, r.t.
–
–
24
7
65
75
59
54
70
72
60
EtOH, refux
EtOH, refux
EtOH, refux
EtOH/H2O, refux
H2O, refux
H2O, 60 °C
Piperidine
Et3N
3
3
7
7
–
–
–
–
–
–
–
12
24
24
24
24
H2O, r.t.
20
CH3CN, refux
CHCl3, refux
DMF, refux
Trace
n.r.
Trace
Bold numbers represent the best values
r.t. room temperature, n.r. no reaction
As shown in Table 2, various primary amines, isatin
derivatives, and barbituric acids were tolerated. The reac-
tion proceeds cleanly under the same reaction conditions to
aford a series of spiro[indolinepyranopyrimidine] deriva-
tives 5a–5i in 64–81% yields.
Table 2 Products 5a–5i (cf.
Entry
R1
R2
R3
X
Producta
Time/h
Yield/%
Scheme 2)
1
2
3
4
5
6
7
8
9
CH3
CH3
CH3
CH(CH3)2
CH2CH3
CH3
CH2Ph
CH2Ph
CH2Ph
CH2Ph
CH3
H
H
H
H
H
H
H
H
H
H
H
H
CH3
H
CH3
H
O
O
O
O
O
O
O
O
S
5a
5b
5c
5d
5e
5f
5g
5h
5i
9
7
7
8
8
9
9
10
10
68
64
72
75
70
81
68
67
70
aVarious amines (1 mmol), nitroketene dithioacetal (1 mmol), isatin (1 mmol), and barbituric acid
(1 mmol) were used. The reactions were run in refuxing water, without any catalyst
1 3

S. Ghadiri et al.
The structures of compounds 5a–5i were elucidated
from their mass, IR, and 1H and 13C NMR spectra. The IR
spectrum of 5a showed absorption bonds due to the NH
groups at 3267 and 3194 cm−1, and C=O groups at 1721 and
1615 cm−1. Stretching frequencies related to the Ar and NO2
groups appeared at 1528, 1463, and 1384 cm−1, respectively.
The 1H NMR spectrum of 5a exhibited a doublet recognized
as arising from the CH3 group (δ=3.14 ppm, 3JHH =5.1 Hz),
one AB quartet due to CH2 group (4.85 ppm), one mul-
tiplet for NHCH3 group (10.55 ppm) and two singlets for
NH groups (11.19 and 12.58 ppm), together with charac-
teristic signals for the aromatic moiety (6.55–7.51 ppm).
1H-decoupled 13C NMR spectrum showed 20 distinct signals
in agreement with the proposed structure. Resonances due
to CH3, CH2, spiro carbon and three C=O groups appeared
at δ = 29.3, 44.6, 48.2, 156.9, 161.3, and 175.7 ppm,
respectively.
give 8. Thus the intermediate 8 undergoes imine-enamine
tautomerisation to form 9 followed by O-cyclization to form
5 via the elimination of MeSH (Scheme 3).
Conclusion
In conclusion, we have developed a simple, green
and novel one-pot, multi-component synthesis of
spiro[indolinepyranopyrimidine] derivatives, through
sequential Knoevenagel condensation, Michael addition,
and O-cyclization sequences in refuxing water, without
any catalyst. This procedure ofers several advantages, such
as use of water as a green solvent, good yields of products,
easy accessibility of reactants, easy workup procedure, and
high atom economy.
A plausible mechanistic pathway for the formation of
5 is outlined in Scheme 3. Initially, the Knoevenagel con-
densation between isatin 3 and barbituric acid 4 derivatives
afords 7 which undergoes Michael addition with N-alkyl-
1-(methylthio)-2-nitroethenamine 6 (derived from the addi-
tion of various amines 1 to nitroketene dithioacetal 2) to
Experimental
The various amines, nitroketene dithioacetal, isatin,
barbituric acid, and other chemicals and solvents were
obtained from Merck and Aldrich and were used without
O2N
H
SCH3
SCH3
Scheme 3
NH2R1
2
1
- MeSH
R3
N
X
O
O
H
X
O
R3
O
R3
O
O2N
H
N R1
SCH3
N
Knoevenagel
condensation
N
N
R3
O
R2
N
N
R2
O
6
7
3
4
Michael
addition
R3
N
R3
N
R2
R2
O
X
O
R2
O
N
X
O
N
N
N
O
O
O2N
N
R3
R3
X
R3
H
imine-enamine
tautomerism
N
O-cyclization
OH
OH
NO2
N
R1
H
NO2
NH
R1
- MeSH
H3CS
N
R1
O
N
H3CS
R3
8
5
9
X = O, S
R1 = CH3, CH2CH3, CH(CH3)2, CH2Ph
R2 = H, CH3, CH2Ph
R3 = H, CH3
1 3

A simple and environmentally benign synthesis of novel…
further purifcation. NMR spectra were recorded with a
Bruker DRX-300 Avance instrument (300 MHz for 1H and
75.4 MHz for 13C) with DMSO-d6 and CDCl3 as solvent.
Chemical shifts are given in ppm (δ), and coupling constant
(J) are reported in hertz (Hz). Melting points were measured
with an electrothermal 9100 apparatus. Mass spectra were
recorded with an Agilent 5975C VL MSD with Triple-Axis
Detector operating at an ionization potential of 70 eV. IR
spectra were measured with Bruker Tensor 27 spectrometer.
Elemental analyses for C, H, and N were performed using a
PerkinElmer 2004 series [II] CHN elemental analyzer.
7′‑(Methylamino)‑6′‑nitrospiro[indoline‑3,5′‑pyrano
[2,3‑d]pyrimidine]‑2,2′,4′(1′H,3′H)‑trione (5c, C15H11
N5O6) White solid; m.p.: 354–356 °C (dec.); yield: 0.257 g
(72%); IR (KBr): ̄ꢀ =3382 and 3235 (NH), 1725 (C=O), 1693
(C=O), 1531 (Ar), 1472 and 1325 (NO2) cm−1; MS (EI, 70 eV):
m/z (%)=357 (M+, 39), 313 (9), 283 (63), 240 (100), 197 (94),
168 (85), 140 (55), 103 (35), 57 (69); 1H NMR (300 MHz,
DMSO-d6): δ=3.09 (s, 3H), 6.67–7.12 (m, 4H), 10.45 (s, 2H),
11.10 (s, 1H), 12.45 (br s, 1H) ppm; 13C NMR (75.4 MHz,
DMSO-d6): δ=29.2 (NHCH3), 48.4 (C-spiro), 89.4, 107.8,
108.9, 121.3, 123.3, 128,5, 131.0, 144.8, 149.4, 151.8, 156.9
(C=O), 161.1 (C=O), 176.7 (C=O) ppm.
General procedure for the synthesis of product 5
7′‑(Isopropylamino)‑6′‑nitrospiro[indoline‑3,5′‑pyran
o[2,3‑d]pyrimidine]‑2,2′,4′(1′H,3′H)‑trione (5d, C17H15
N5O6) White solid; m.p.: 255–260 °C (dec.); yield: 0.288 g
(75%); 1H NMR (300 MHz, DMSO-d6): δ=1.13 (d, 3H), 1.30
(d, 3H), 4.15–4.30 (m, 1H), 6.60–7.05 (m, 4H), 7.60 (br s,
1H), 9.30 (s, 1H), 10.15 (s, 1H), 10.65 (d, 1H) ppm; 13C NMR
(75.4 MHz, DMSO-d6): δ=20.8 (CH3), 22.8 (CH3), 44.6 (CH),
49.5 (C-spiro), 85.0, 108.4, 108.6, 120.7, 122.4, 127.5, 132.8,
144.9, 157.8, 158.4, 161.3 (C=O), 163.8 (C=O), 178.1 (C=O)
ppm.
A mixture of various amines (1 mmol), 0.165 gnitroketene
dithioacetal (1 mmol) and 10 cm3 H2O in a 50 cm3 fask was
refuxed for 6 h. After completion of the reaction (moni-
tored by TLC, ethyl acetate/n-hexane, 6:4), isatin derivatives
(1 mmol) and barbituric acids (1 mmol) were added to the
reaction mixture, and it was stirred under refux for 7–10 h.
Then, the reaction mixture was cooled to room temperature
and fltered to give the crude product. The solid was washed
with water to give pure product 5 in good yield.
1‑Benzyl‑7′‑(methylamino)‑6′‑nitrospiro[indoline‑3
,5′‑pyrano[2,3‑d]pyrimidine]‑2,2′,4′(1′H,3′H)‑trione
(5a, C22H17N5O6) White solid; m.p.: 308–310 °C (dec.);
yield: 0.304 g (68%); IR (KBr): ̄ꢀ = 3267 and 3194 (NH),
1721 (C=O), 1615 (C=O), 1528 (Ar), 1463 and 1384 (NO2)
cm−1; MS (EI, 70 eV): m/z (%)=447 (M+, 11), 390 (9), 347
(5), 299 (30), 247 (10), 169 (8), 91 (100), 51 (2); 1H NMR
(300 MHz, DMSO-d6): δ=3.14 (d, 3JHH =5.1 Hz, 3H), 4.85
(AB q, 2H), 6.55 (d, 3JHH =7.5 Hz, 1H), 6.86 (t, 1H), 7.07 (t,
1H), 7.21–7.30 (m, 4H), 7.51 (d, 3JHH =7.2 Hz, 2H), 10.55
(m, 2H), 11.19 (s, 1H), 12.58 (br s, 1H) ppm; 13C NMR
(75.4 MHz, DMSO-d6): δ=29.3 (NHCH3), 44.6 (CH2), 48.2
(C-spiro), 89.3, 107.5, 108.4, 122.2, 123.3, 127.4, 127.6,
128.6, 128.7, 130.3, 137.1, 145.6, 149.3, 151.9, 156.9
(C=O), 161.3 (C=O), 175.7 (C=O) ppm.
7′‑(Ethylamino)‑6′‑nitrospiro[indoline‑3,5′‑pyran
o[2,3‑d]pyrimidine]‑2,2′,4′(1′H,3′H)‑trione (5e, C16
H13N5O6) White solid; m.p.: 306–312 °C (dec.); yield:
0.259 g (70%); 1H NMR (300 MHz, DMSO-d6): δ=1.24 (t,
3JHH =6.9 Hz, 3H), 3.51–3.59 (m, 2H), 6.68–7.12 (m, 4H),
10.47 (s, 1H), 10.59 (t, 3JHH =5.7 Hz, 1H), 11.12 (s, 1H) ppm;
13C NMR (75.4 MHz, DMSO-d6): δ=15.6 (CH3), 37.5 (CH2),
48.4 (C-spiro), 89.4, 107.6, 108.9, 121.3, 123.3, 128.5, 131.0,
144.8, 149.3, 151.7, 156.4 (C=O), 161.1 (C=O), 176.7 (C=O)
ppm.
1′,3′‑Dimethyl‑7′‑(methylamino)‑6′‑nitrospiro[indoli
ne‑3,5′‑pyrano[2,3‑d]pyrimidine]‑2,2′,4′(1′H,3′H)‑tri
one (5f, C17H15N5O6) White solid; m.p.: 287–289 °C (dec.);
yield: 0.312 g (81%); IR (KBr): ̄ꢀ =3431 and 3192 (NH),
1726 (C=O), 1687 (C=O), 1455 and 1355 (NO2) cm−1; MS
(EI, 70 eV): m/z (%)=385 (M+, 53), 339 (55), 324 (100),
280 (37), 228 (24), 197 (41), 157 (31), 114 (22), 58 (35);
1H NMR (300 MHz, DMSO-d6): δ=3.00 (s, 3H), 3.16 (d,
3JHH =4.8 Hz, 3H), 3.45 (s, 3H), 6.69–7.11 (m, 4H), 10.48
(s, 1H) ppm; 13C NMR (75.4 MHz, DMSO-d6): δ = 28.2
(NHCH3), 29.4 (NCH3), 30.0 (NCH3), 48.9 (C-spiro), 90.0,
107.8, 108.9, 121.2, 123.4, 128.6, 130.9, 144.9, 149.7, 150.7,
156.6 (C=O), 159.0 (C=O), 176.6 (C=O) ppm.
1‑Methyl‑7′‑(methylamino)‑6′‑nitrospiro[indoline‑3
,5′‑pyrano[2,3‑d]pyrimidine]‑2,2′,4′(1′H,3′H)‑trione
(5b, C16H13N5O6) White solid; m.p.: 320–322 °C (dec.);
yield: 0.237 g (64%); IR (KBr): ̄ꢀ =3246 (NH), 1711 (C=O),
1656 (C=O), 1533 (Ar), 1467 and 1388 (NO2) cm−1; MS
(EI, 70 eV): m/z (%) = 371 (M+, 60), 310 (44), 284 (25),
240 (11), 211 (100), 171 (83), 143 (18), 114 (24), 91 (30),
57 (17); 1H NMR (300 MHz, DMSO-d6): δ=3.11 (s, 6H),
6.87–7.19 (m, 4H), 10.48 (m, 1H), 11.11 (s, 1H), 12.55 (br s,
1H) ppm; 13C NMR (75.4 MHz, DMSO-d6): δ=26.9 (CH3),
29.2 (CH3), 48.0 (C-spiro), 89.3, 107.4, 107.7, 122.0, 123.1,
128.7, 130.3, 146.2, 149.3, 151.8, 156.9 (C=O), 161.0
(C=O), 175.4 (C=O) ppm.
7′‑(Benzylamino)‑6′‑nitrospiro[indoline‑3,5′‑pyrano
[2,3‑d]pyrimidine]‑2,2′,4′(1′H,3′H)‑trione (5g, C21H15
N5O6) Orange solid; m.p.: 240–242 °C (dec.); yield: 0.294 g
(68%); IR (KBr): ̄ꢀ =3422 and 3217 (NH), 1702 (C=O), 1687
1 3

S. Ghadiri et al.
2. Akhlaghi MF, Amidi S, Esfahanizadeh M, Daeihamed M, Kobar-
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(C=O), 1641 (C=O), 1605 (Ar), 1515 and 1326 (NO2), 1461
and 1388 (NO2) cm−1; MS (EI, 70 eV): m/z (%)=433 (M+,
2), 417 (6), 283 (9), 240 (20), 197 (19), 168 (25), 133 (45), 91
(100), 51 (19); 1H NMR (300 MHz, DMSO-d6): δ=4.63 (ABX,
JAB =66 Hz, JAX =JBX =5.7 Hz, δA=4.52 and δB=4.74 ppm,
2H), 7.18–7.72 (m, 9H), 8.20 (t, 1H), 9.37 (t, 3JHH =5.7 Hz,
1H) ppm; 13C NMR (75.4 MHz, DMSO-d6): δ=43.2 (CH2),
44.4 (C-spiro), 118.5, 124.3, 126.6, 127.1, 127.6, 127.9, 128.1,
128.6, 128.8, 129.8, 133.6, 138.8, 140.1, 141.7, 147.9, 149.0,
163.5 (C=O) ppm.
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7′‑(Benzylamino)‑1′,3′‑dimethyl‑6′‑nitrospiro[indo
line‑3,5′‑pyrano[2,3‑d]pyrimidine]‑2,2′,4′(1′H,3′H)‑
trione (5h, C19H19N5O6) White solid; m.p.: 306–312 °C
(dec.); yield: 0.309 (67%); 1H NMR (300 MHz, DMSO-d6):
δ=2.96 (s, 3H), 3.23 (s, 3H), 4.82 (A2X, d, JAX =6.0 Hz,
δA =4.82, 2H), 6.70–7.43 (m, 9H), 10.53 (s, 1H), 10.98 (t,
3JHH =6.0 Hz, 1H) ppm; 13C NMR (75.4 MHz, DMSO-d6):
δ=28.2 (NCH3), 29.9 (NCH3), 45.9 (CH2), 48.9 (C-spiro),
90.0, 108.2, 109.0, 121.3, 123.4, 127.2, 128.0, 128.7129.2,
130.8, 137.6, 144.9, 149.6, 150.6, 156.2 (C=O), 159.0
(C=O), 176.6 (C=O) ppm.
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7 ′ ‑ ( B e n z y l a m i n o ) ‑ 6 ′ ‑ n i t r o ‑ 2 ′ ‑ t h i oxo ‑ 2 ′ , 3 ′ ‑
d i h y d r o s p i r o [ i n d o l i n e ‑ 3 , 5 ′ ‑ p y r a n o [ 2 , 3 ‑ d]
pyrimidine]‑2,4′(1′H)‑dione (5i, C21H15N5O5S5) Orange
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1
solid; m.p.: 240–242 °C (dec.); yield: 0.314 g (70%); H
NMR (300 MHz, DMSO-d6): δ=4.63 (ABX, JAB =65 Hz,
JAX =JBX =5.4 Hz, δA =4.52 and δB =4.74, 2H), 7.18–7.67
(m, 11H), 8.17 (br s, 1H), 9.35 (br s, 1H) ppm; 13C NMR
(75.4 MHz, DMSO-d6): δ = 43.2 (CH2), 44.5 (C-spiro),
118.5, 124.3, 126.6, 127.1, 127.6, 127.9, 128.1, 128.6,
128.8, 129.8, 133.6, 138.8, 140.1, 141.7, 147.9, 149.0, 163.5
(C=S) ppm.
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M (2013) Daru J Pharm Sci 21:3
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Chem Iasi 24:20
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29. Reheim MAMA, Hafz ISA, Elian MA (2016) Heterocycl Com-
mun 22:311
30. Bhat AR, Shalla AH, Dongre RS (2016) J Taibah Univ Sci 10:9
Acknowledgements We gratefully acknowledge the fnancial support
of this research from Imam Khomeini International University.
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