One-pot synthesis of 4-ethyl 2,3-dimethyl 1-(5-aryl-1,3,4-thiadiazol-2-yl)-5-oxo-2,5-dihydro-1H-pyrrole-2,3,4-tricarboxylate derivatives via intramolecular Wittig reaction

Article abstract of DOI:10.1177/1747519820903291

A facile one-pot synthesis of highly functionalized dialkyl 1-(5-aryl-1,3,4-thiadiazol-2-yl)-4-ethoxy-5-oxo-2,5-dihydro-1H-pyrrole-2,3-dicarboxylate derivatives via the reaction between acetylenic esters, triphenylphosphine, and ethyl 2-[(5-aryl-1,3,4-thi

Full text of DOI:10.1177/1747519820903291

903291CHL0010.1177/1747519820903291Journal of Chemical ResearchIravani and Esmaeili
research-article2020
Research Paper
Journal of Chemical Research
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One-pot synthesis of 4-ethyl 2,3-dimethyl
1-(5-aryl-1,3,4-thiadiazol-2-yl)-5-oxo-2,5-dihydro-
1H-pyrrole-2,3,4-tricarboxylate derivatives via
intramolecular Wittig reaction
https://doi.org/10.1177/1747519820903291
DOI: 10.1177/1747519820903291
journals.sagepub.com/home/chl
Samin Iravani and Abbas Ali Esmaeili
Abstract
A facile one-pot synthesis of highly functionalized dialkyl 1-(5-aryl-1,3,4-thiadiazol-2-yl)-4-ethoxy-5-oxo-2,5-dihydro-1H-
pyrrole-2,3-dicarboxylate derivatives via the reaction between acetylenic esters, triphenylphosphine, and ethyl 2-[(5-aryl-
1,3,4-thiadiazol-2-yl)amino]-2-oxoacetate is developed. The structure of the products is confirmed by spectroscopic
methods.
Keywords
acetylenic esters, intramolecular Wittig reaction, pyrrolidinone, ethyl 2-[(5-aryl-1,3,4-thiadiazol-2-yl)amino]-2-
oxoacetate, triphenylphosphine
Date received: 19 October 2019; accepted: 8 January 2020
One-pot synthesis of 4-ethyl 2,3-dimethyl 1-(5-aryl-1,3,4-thiadiazol-2-yl)-5-oxo-2,5-dihydro-1H-pyrrole-2,3,4-tricarboxylate
derivatives via intramolecular Wittig reaction.
B).10,11 As for other examples, and compound C displays
Introduction
both antibacterial along with antifungal activity, while
Exhibiting interesting biological behavior, heterocyclic
compound D is an effective antitumor agent (Figure 1).12
compounds have found a special place in the pharmaceuti-
Moreover, 2-pyrrolidinones, as a class of five-mem-
cal industry.1,2 Many substances containing five-membered
bered lactams with a four-carbon heterocyclic ring struc-
heterocycles demonstrate a variety of interesting biological
ture, are of interest to biologists.13,14 2-Pyrrolidinone play
activities. In this category, 1,3,4-thiadiazoles and 2-pyrroli-
a significant role in natural products and pharmaceuticals.
dinones have been used as structural motifs in the construc-
Some known biologically important natural products
tion of substances having multi-target active, such as
anti-inflammatory,3,4 antimicrobial,5 anticonvulsant,6,7 and
antihypertensive.8,9 1,3,4-Thiadiazoles have also been fre-
quently used as important building blocks for the synthesis
of biologically active heterocyclic molecules. Heterocycles,
bearing a 1,3,4-thiadiazole moiety, are reported to demon-
strate a broad spectrum of biological activity such as antimi-
crobial, tranquilizer, antiepilepsy, antiinflamatory, antiviral,
anti-coagulant, and antitumor (Figure 1, structures A and
Department of Chemistry, Faculty of Science, Ferdowsi University of
Mashhad, Mashhad, Iran
Corresponding author:
Abbas Ali Esmaeili, Department of Chemistry, Faculty of Science,
Ferdowsi University of Mashhad, 9177948974, Mashhad, Iran.
Email: abesmaeili@um.ac.ir

2
Journal of Chemical Research 00(0)
Figure 1. Biologically active thiadiazole and lactam molecules.
amino]acetate derivatives (Scheme 1). Subsequent reac-
tion with triphenylphosphine and acetylenic esters gave
the desired products (Scheme 2).
Results and discussion
Scheme 1. Synthesis of ethyl 2-oxo-2-[(5-aryl-1,3,4-thiadiazol-
2-yl)amino] acetates.
Initially, a model reaction was conducted using triphe-
nylphosphine (1mmol), ethyl (5-benzyl-1,3,4-thiadiazol-
2-ylcarbamoyl)formate (3a) (1mmol), and dimethyl
acetylenedicarboxylate (DMAD) (4a) (1mmol) in CH2Cl2
at room temperature. This model reaction was examined
under different conditions, as shown in Table 1. Upon
changing the solvent, temperature, and amount of triphe-
nylphosphine, it was found that using CH2Cl2 and 1.5 equiv.
of Ph3P the desired product can be afforded in 70% yield in
24h (Table 1, entry 8).
Ultimately, CH2Cl2, room temperature, and 1.5mmol triph-
enylphosphine were selected as the optimized conditions.
With optimized conditions established, we next tested the
scope of various reactants. Ethyl 2-oxo-2-[(5-aryl-1,3,4-thia-
diazol-2-yl)amino]acetates 3 were examined in reactions with
dialkyl acetylenedicarboxylates 4 in the presence of Ph3P via a
one-pot procedure leading to the corresponding products 5a–n
in 48%–85% yields (Table 2). Ethyl 2-oxo-2-[(5-aryl-1,3,4-
thiadiazol-2-yl)amino] acetates containing electron-donating
groups at positions 5, such as benzyl-, phenyl-, 4-methyl-
phenyl-, and 3-methyphenyl-thiadiazole, exhibited good
reactivities (5, 51%–71% yield). Ethyl 2-oxo-
2-[(5-aryl-1,3,4-thiadiazol-2-yl)amino] containing elec-
tron-withdrawing groups such as 4-bromophenyl group were
also well tolerated (5i, 85% and 5n, 48%).
comprising a 2-pyrrolidinone unit are cotinine, a tobacco
alkaloid,15 doxapram, a respiratory stimulatant,16 and etho-
suximide, a succinimide containing anticonvulsant.17
Moreover, substituted 2-pyrrolidinone derivatives have
various therapeutic properties, for example, anti-cancer,18
antitumor,19 HIV-1 integrase inhibition,20,21 antimicro-
bial,22 antibacterial,23 and anti-inflammatory.24 In addition,
the 2-pyrrolidinone moiety is used in the drug PI-091, con-
sisting of anti-coagulant properties, as well as in Jatropham,
which is an antitumor alkaloid (Figure 1, structures E and
F).25,26 Due to their importance, a variety of synthetic pro-
tocols have been reported for the preparation of substituted
pyrrolidinones.27–36
The Wittig reaction of phosphonium ylides with car-
bonyl compounds has been adopted widely for the con-
struction of C=C double bonds in an inter- or
intramolecular approach under mild reaction condi-
tions.37,38 The intramolecular Wittig reaction is one of the
most common methods for the synthesis of different five-
membered heterocycles through intramolecular cycliza-
tion of phosphorus ylides with various carbonyl groups,
such as aldehyde, ketone, ester, amide, and imide.39–43 To
date, a number of synthetic approaches to pyrrolidinones
structures have been developed.44–49 In 2007, Anary-
Abbasinejad et al.50 reported the synthesis of novel highly
functionalized pyrrolidinones via intramolecular Wittig
reactions. Inspired by the biological profiles of 1,3,4-thi-
adiazoles and pyrrolidinones and as part of our interest in
the synthesis of heterocyclic compounds via intramolecu-
lar Wittig reactions,51,52 we sought to synthesize the title
compounds. For this purpose, first ethyl chlorooxoacetate
was reacted with 2-amino-1,3,4-thiadiazoles for the syn-
thesis of ethyl 2-oxo-2-[(5-aryl-1,3,4-thiadiazol-2-yl)
The structure elucidation of compounds 5a–n was car-
1
ried out on the basis of H NMR, 13C NMR, Fourier-
transform
infrared
spectroscopy
(FTIR),
mass
spectrometry, and elemental analysis (Supplemental mate-
rial). For example, the 1H NMR spectrum of 5a contained
3
a triplet for CH3 (1.42ppm, JHH = 6.0Hz), two singlets
for CH3O (3.84 and 3.85ppm), a singlet for PhCH2
3
(4.36ppm), a quartet for OCH2 (4.75ppm, JHH = 6.0Hz),
a singlet for CH (5.58ppm), and a multiplet for ArH (7.28–
7.34ppm). The 1H-decoupled 13C NMR spectrum of 5a is

Iravani and Esmaeili
3
Scheme 2. Synthesis of the final products.
Table 1. Optimization of the reaction conditions.
Entry
Solvent
Time (h)
Temperature
Yield (%)
1
2
3
4
5
6
7
8
9
EtOAc
MeCN
MeCN
EtOH
THF
DMF
Et2O
CH2Cl2
CH2Cl2
24
24
24
24
24
24
24
24
12
r.t.
r.t.
Reflux
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
50
65
65
43
27
10
60
70
50
Table 2. Synthesis of compounds 5a–n.
Product
R1
R2
Yield (%)
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
5m
5n
C6H5–CH2–
4-Me–C6H4–
3-Me–C6H4–
C6H5–
C6H5–CH2–
4-Me–C6H4–
3-Me–C6H4–
C6H5–
4-Br–C6H4–
C6H5–CH2–
4-Me–C6H4–
3-Me–C6H4–
C6H5–
Me
Me
Me
Me
Et
Et
Et
Et
Et
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
70
55
79
57
51
54
71
69
85
71
67
61
72
48
4-Br–C6H4–
in agreement with the suggested structure. The mass spec- due to the nonconjugated, conjugated, and Y-lactam car-
trum of 5a, for example, demonstrated the molecular ion bonyl groups.
peak at m/z=418. Also, the IR spectrum of compound 5a
The reaction mechanism is presented in Scheme 3. The
showed absorption bands at 1750, 1641, and 1702 cm−1 initial step is formation of zwitterion intermediate A from

4
Journal of Chemical Research 00(0)
Scheme 3. The mechanism of reaction.
the reaction of Ph3P and dicarboxylate 4. Next, the interme-
diate A is protonated by the NH amide of 3 to produce triph-
enylphosphonium salt B. The resulting phosphonium salt B
is attacked by the conjugate base of the NH acid to give
ylide C, which undergoes intramolecular cyclization to pro-
duce triphenylphosphine oxide and product 5 (Scheme 3).
Dimethyl 1-(5-benzyl-1,3,4-thiadiazol-
2-yl)-4-ethoxy-2,5-dihydro-5-oxo-1H-
pyrrole-2,3-dicarboxylate (5a); typical
procedure
To a stirred solution of ethyl (5-benzyl-1,3,4-thiadiazol-
2-ylcarbamoyl)formate (5a; 0.291g, 1mmol) and Ph3P
(0.393g, 1.5mmol) in CH2Cl2 (10mL) at room tempera-
ture was added dropwise a solution of DMAD (0.142g,
1.0mmol) in CH2Cl2 (2mL) over 10min. The reaction
mixture was stirred for 24h. The solvent was removed
under reduced pressure to afford the crude product, which
was purified by column chromatography on silica gel
(hexane/EtOAc) to obtain the dimethyl 1-(5-benzyl-1,3,4-
thiadiazol-2-yl)-4-ethoxy-2,5-dihydro-5-oxo-1H-pyrrole-
2,3-dicarboxylate (5a) (0.292g, 70%) as a pale yellow
powder.
Conclusion
In summary, we have established that the one-pot reac-
tionbetweenPh3P,acetylenicesters4and2-[(5-aryl-1,3,4-
thiadiazol-2-yl)amino]-2-oxoacetates
3 represents a
simplemethodforthepreparationofdialkyl1-(5-aryl-1,3,4-
thiadiazol-2-yl)-4-ethoxy-5-oxo-2,5-dihydro-1H-pyr-
role-2,3-dicarboxylates 5 of potential synthetic and
pharmacological interest. The ready availability of the
starting materials, the simplicity of the reaction, and
mild conditions are among the distinguishing features of
this method. The present method is applied under neutral
conditions with no prior activation required.
Pale yellow powder (0.292g, 70%), m.p. 118°C–119°C;
IR (KBr) (υmax/cm−1): 1750, 1702, 1641 (3 C=O); 1H NMR
(300.13MHz,CDCl ):δ(ppm)=1.42(3H,t, 3 JHH = 6.0Hz,
3
CH2CH3), 3.84 (3H, s, OCH3), 3.85 (3H, s, OCH3), 4.36
3
(2H, s, CH2), 4.75 (2H, q, JHH = 9.0Hz , OCH2), 5.58
(1H, s, CH), 7.28–7.34 (5H, m,ArH); 13C NMR (75.46MHz,
CDCl3): δ (ppm) = 15.63, 36.42, 52.36, 53.63, 59.88,
69.09, 114.46, 127.55, 128.88, 129.06, 136.66, 152.44,
156.38, 161.58, 162.48, 166.04, 167.53; MS m/z (%) = 418
(M++1, 37), 416 (100), 401 (38), 355 (10), 312 (85), 294
(43), 266 (50), 200 (17), 148 (45), 90 (47), 59 (10), 29 (22).
Anal. calcd for C19H19N3O6S (417.44): C, 54.67; H, 4.59;
N, 10.07%. Found: C, 54.94; H, 4.59; N, 10.35%.
Experimental
Melting points were determined on an Electrothermal
9100 apparatus. Infrared (IR) spectra were recorded using
a Nicolet Avatar 370 FTIR Therma spectrometer as KBr
pellets and are reported in cm−1. H NMR and 13C NMR
1
spectra were recorded on a Bruker DPX-300 Avance
instrument at 300 and 75.47MHz, respectively. CDCl3
were used as the solvent and shifts are given in ppm.
Elemental analyses were performed using a Thermo
Finnegan Flash EA 1112 series instrument. Mass spectra
were recorded with a Varian Meth ch-7 at 70eV. Column
chromatography was performed on silica gel (160–200
mesh, E. Merck). Thiadiazole derivatives 3, were prepared
according to the literature source.53
Dimethyl 4-ethoxy-5-oxo-1-[5-(p-tolyl)-1,3,4-thiadia-
zol-2-yl]-2,5-dihydro-1H-pyrrole-2,3-dicarboxylate (5b):
White powder: (0.300g, 55%), m.p. 178°C; IR (KBr)
(υmax/cm−1): 1747, 1725, 1698 (3 C=O), 1H NMR
3
(300.13MHz,CDCl3):δ(ppm)=1.49(3H,t, JHH = 9.0Hz,
CH2CH3), 2.44 (3H, s, OCH3), 3.89 (3H, s, OCH3), 3.90
3
(3H, s, CH3), 4.83 (2H, q, JHH = 6.0Hz , OCH2), 5.68

Iravani and Esmaeili
5
3
3
(1H, s, CH), 7.31 (2H, d, JHH = 9.0Hz , 2 CHAr), 7.85 1.34 (3H, t, JHH = 9.0Hz , OCH2CH3), 1.44 (3H, t,
3
(2H, d, JHH = 9.0Hz , 2 CHAr); 13C NMR (75.46MHz, 3 JHH = 6.0Hz , OCH2CH3), 2.39 (3H, s, CH3), 4.24–4.33
CDCl3): δ (ppm)=10.91, 16.76, 47.65, 48.95, 55.25, 64.28, (4H, m, OCH2), 4.76 (2H, q, JHH = 9.0Hz , OCH2), 5.63
3
3
109.71, 122.50, 122.62, 125.14, 136.73, 147.77, 150.45, (1H, s, CH), 7.26 (2H, d, JHH = 9.0Hz , 2 CHAr), 7.81 (2H,
3
156.87, 157.78, 159.94, 162.78; MS m/z (%)=417 (M+, d, JHH = 9.0Hz , 2 CHAr); 13C NMR (75.46MHz, CDCl3):
55), 416 (100), 355 (17), 312 (100), 294 (65), 266 (85), 200 δ (ppm) = 13.97, 14.05, 15.53, 21.44, 60.20, 61.45, 62.77,
(30), 173 (27), 134 (30), 116 (22), 59 (25), 28 (17). Anal. 69.17, 114.72, 127.23, 127.31, 129.81, 141.34, 152.29,
calcd for C19H19N3O6S (417.44): C, 54.67; H, 4.59; N, 155.20, 161.02, 162.60, 164.54, 166.83; MS m/z (%) = 445
10.07%. Found: C, 54.91; H, 4.39; N, 9.77%.
(M+, 100), 369 (42), 340 (92), 312 (98), 294 (93), 266 (100),
Dimethyl 4-ethoxy-5-oxo-1-[5-(m-tolyl)-1,3,4-thiadia- 200 (50), 174 (47), 134 (38), 116 (65), 29 (100). Anal. calcd
zol-2-yl]-2,5-dihydro-1H-pyrrole-2,3-dicarboxylate (5c): for C21H23N3O6S (445.49): C, 56.62; H, 5.20; N, 9.43%.
White powder: (0.330g, 79%), m.p. 160°C–162°C; IR Found: C, 56.76; H, 5.10; N, 9.62%.
1
(KBr) (υmax/cm−1): 1748, 1719, 1702 (3 C=O); H NMR
Diethyl 4-ethoxy-5-oxo-1-[5-(m-tolyl)-1,3,4-thiadiazol-
3
(300.13MHz, CDCl3): δ (ppm)=1.45 (3H, t, JHH = 6.0Hz 2-yl]-2,5-dihydro-1H-pyrrole-2,3-dicarboxylate (5g): White
, CH2CH3), 2.40 (3H, s, OCH3), 3.85 (3H, s, OCH3), 3.85 powder (0.318g, 71%), m.p. 97°C–98°C; IR (KBr) (υmax
/
3
1
(3H, s, CH3), 4.78 (2H, q, JHH = 9.0Hz , OCH2), 5.64 cm−1): 1754, 1726, 1699 (3 C=O); H NMR (300.13MHz,
3
(1H, s, CH), 7.26–7.76 (4H, m,ArH); 13C NMR (75.46MHz, CDCl3): δ (ppm) = 1.31 (3H, t, JHH = 6.0Hz , CH2CH3),
3
CDCl3): δ (ppm)=15.60, 36.42, 52.33, 53.61, 59.84, 69.06, 1.35 (3H, t, JHH = 6.0Hz , OCH2CH3), 1.44 (3H, t,
77.20, 84.84, 114.39, 127.53, 128.85, 129.03, 136.60, 3 JHH = 6.0Hz , OCH2CH3), 2.41 (3H, s, CH3), 4.25–4.34
3
152.42, 156.35, 161.56, 162.29, 166.04, 167.50; MS m/z (4H, m, OCH2), 4.76 (2H, q, JHH = 6.0Hz , OCH2), 5.65
(%)=418 (M++1, 40), 415 (100), 400 (22), 356 (35), 312 (1H, s, CH), 7.29–7.37 (4H, m, ArH); 13C NMR (75.46MHz,
(95), 267 (95), 200 (78), 173 (83), 134 (70), 117 (95), 91 CDCl3): δ (ppm)=14.06, 15.54, 21.29, 60.26, 61.48, 62.79,
(48), 59 (95), 29 (67). Anal. calcd for C19H19N3O6S 69.20, 84.84, 114.70, 124.63, 127.94, 129.02, 129.84,
(417.44): C, 54.67; H, 4.59; N, 10.07%. Found: C, 54.35; 131.72, 138.99, 152.29, 155.40, 161.02, 162.63, 164.63,
H, 4.34; N, 9.81%.
166.84; MS m/z (%)=445 (M+, 100), 397 (5), 369 (58), 340
Dimethyl 4-ethoxy-5-oxo-1-[5-phenyl-1,3,4-thiadiazol- (90), 313 (100), 294 (90), 266 (100), 200 (50), 174 (55), 134
2-yl]-2,5-dihydro-1H-pyrrole-2,3-dicarboxylate (5d): pale (33), 116 (60), 90 (18), 30 (85). Anal. calcd for C21H23N3O6S
yellow powder: (0.228g, 57%), m.p. 153°C–154°C; IR (KBr) (445.49): C, 56.62; H, 5.20; N, 9.43%. Found: C, 56.90; H,
(υmax/cm−1):1750,1720,1699(3C=O),1HNMR(300.13MHz, 4.96; N, 9.14%.
3
CDCl3): δ (ppm)=1.45 (3H, t, JHH = 6.0Hz , CH2CH3),
Diethyl 4-ethoxy-5-oxo-1-[5-phenyl-1,3,4-thiadiazol-
3.85 (3H, s, OCH3), 3.85 (3H, s, OCH3), 4.79 (2H, q, 2-yl]-2,5-dihydro-1H-pyrrole-2,3-dicarboxylate (5h): White
3 JHH = 6.0Hz , OCH2), 5.65 (1H, s, CH), 7.70 (5H, m, ArH); powder (0.308g, 69%), m.p. 99°C–101°C; IR (KBr) (υmax
/
13C NMR (75.46MHz, CDCl3): δ (ppm)=15.60, 52.37, 53.66, cm−1): 1736, 1719, 1701 (3 C=O); H NMR (300.13MHz,
1
3
59.95, 69.20, 114.44, 127.39, 129.16, 129.92, 130.97, 152.41, CDCl3): δ (ppm)=1.31 (3H, t, JHH = 6.0Hz , CH2CH3),
3
155.44, 161.55, 162.52, 164.49, 167.46; MS m/z (%)=403 1.35 (3H, t, JHH = 6.0Hz , OCH2CH3), 1.44 (3H, t,
(M+, 10), 400 (100), 298 (47), 280 (25), 253 (33), 202 (10), 3 JHH = 6.0Hz , OCH2CH3), 4.25–4.34 (4H, m, OCH2), 4.76
3
160 (20), 103 (13), 59 (8), 29 (30).Anal. calcd for C18H17N3O6S (2H, q, JHH = 6.0Hz , OCH2), 5.64 (1H, s, CH), 7.45–7.94
(403.41): C, 53.59; H, 4.25; N, 10.42%. Found: C, 53.37; H, (5H, m, ArH); 13C NMR (75.46MHz, CDCl3):
δ
3.96; N, 10.22%.
(ppm)=13.98, 14.06, 15.54, 60.21, 61.49, 62.81, 69.21,
Diethyl 1-[5-benzyl-1,3,4-thiadiazol-2-yl]-4-ethoxy- 114.75, 127.41, 129.14, 129.97, 130.91, 152.25, 155.51,
5-oxo-2,5-dihydro-1H-pyrrole-2,3-dicarboxylate (5e): pale 161.01, 162.65, 164.42, 166.82; MS m/z (%)=431 (M+,
yellow liquid; (0.226g, 51%); IR (KBr) (υmax/cm−1): 1740, 100), 416 (13), 364 (45), 355 (85), 327 (87), 299 (87), 253
1
1722, 1638 (3 C=O); H NMR (300.13MHz, CDCl3): δ (93), 166 (79), 160 (79), 102 (79), 76 (68), 52 (32), 29 (95).
3
(ppm) = 1.29 (3H, t, JHH = 6.0Hz , CH2CH3), 1.33 (3H, t, Anal. calcd for C20H21N3O6S (431.46): C, 55.68; H, 4.91; N,
3
3 JHH = 6.0Hz , OCH2CH3), 1.39 (3H, t, JHH = 6.0Hz , 9.74%. Found: C, 55.58; H, 4.83; N, 9.60%.
OCH2CH3), 4.24–4.32 (4H, m, OCH2), 4.34 (2H, s, CH2),
Diethyl 1-[5-(4-bromophenyl)-1,3,4-thiadiazol-2-yl]-4-eth-
3
4.71 (2H, q, JHH = 9.0Hz , OCH2) 5.58 (1H, s, CH), 7.24– oxy-5-oxo-2,5-dihydro-1H-pyrrole-2,3-dicarboxylate (5i):
7.35 (5H, m, ArH); 13C NMR (75.46MHz, CDCl3): δ (ppm) White powder (0.432g, 85%), m.p. 128°C–129°C; IR (KBr)
= 14.04, 15.52, 36.38, 60.09, 61.43, 62.73, 69.07, 84.84, (υmax/cm−1):1736, 1726, 1703(3C=O);1HNMR(300.13MHz,
3
114.67, 127.49, 128.81, 129.00, 136.64, 152.28, 156.41, CDCl3): δ (ppm)= 1.31 (3H, t, JHH = 6.0Hz , CH2CH3), 1.35
160.99, 162.56, 165.97, 166.87; MS m/z (%) = 445 (M+, (3H,t, 3 JHH = 6.0Hz ,OCH CH ),1.44(3H,t, 3 JHH = 6.0Hz
2
3
65), 398 (32), 369 (95), 340 (95), 294 (94), 266 (100), 241 , OCH2CH3), 4.25–4.34 (4H, m, OCH2), 4.75 (2H, q,
(37), 200 (87), 173 (92), 148 (47), 116 (26), 91 (95), 53 (10), 3 JHH = 9.0Hz , OCH2), 5.64 (1H, s, CH), 7.60 (2H, d,
30 (92). Anal. calcd for C21H23N3O6S (445.49): C, 56.62; H, 3 JHH = 9.0Hz , 2 CHAr), 7.80 (2H, d, JHH = 9.0Hz , 2
3
5.20; N, 9.43%. Found: C, 56.35; H, 4.96; N, 9.32%.
CHAr); 13C NMR (75.46MHz, CDCl3): δ (ppm)=13.98, 14.06,
Diethyl 4-ethoxy-5-oxo-1-[5-(p-tolyl)-1,3,4-thiadiazol- 15.52, 60.23, 61.53, 62.85, 69.26, 84.84, 114.84, 125.31,
2-yl]-2,5-dihydro-1H-pyrrole-2,3-dicarboxylate (5f): White 128.73, 132.38, 152.15, 155.63, 160.97, 162.69, 163.26,
powder (0.240g, 54%), m.p. 124°C–125°C; IR (KBr) (υmax
/
166.75; MS m/z (%) = 510 (M+, 78), 464 (5), 437 (78), 407
1
cm−1): 1742, 1724, 1710 (3 C=O); H NMR (300.13MHz, (79), 358 (78), 330 (80), 264 (48), 236 (45), 197 (43), 181 (75),
3
CDCl3): δ (ppm)= 1.31 (3H, t, JHH = 9.0Hz , CH2CH3), 125 (55), 98 (50), 53 (45), 30 (100). Anal. calcd for

6
Journal of Chemical Research 00(0)
1
C20H20BrN3O6S (510.36): C, 47.07; H, 3.95; N, 8.23%. Found: (KBr) (υmax/cm−1): 1747, 1720, 1702 (3 C=O); H NMR
C, 47.38; H, 3.94; N, 8.05%.
(300.13MHz,CDCl ):δ(ppm)=1.24(3H,d, 3 JHH = 6.0Hz
3
3
Diisopropyl 1-[5-benzyl-1,3,4-thiadiazol-2-yl]-4-ethoxy- , CHCH3), 1.33 (3H, d, JHH = 6.0Hz , CHCH3), 1.34 (6H,
3
3
5-oxo-2,5-dihydro-1H-pyrrole-2,3-dicarboxylate (5j): Colorless d, JHH = 6.0Hz , 2 CHCH3), 1.44 (3H, t, JHH = 6.0Hz ,
3
liquid (0.336g, 71%); IR (KBr) (υmax/cm−1): 1739, 1719, 1638 CH2CH3), 4.74 (2H, q, JHH = 6.0Hz , OCH2), 5.08 (H,
3
3
(3 C=O); 1H NMR (300.13MHz, CDCl3): δ (ppm) = 1.24 (3H, sep, JHH = 6.0Hz , OCH), 5.16 (H, sep, JHH = 6.0Hz ,
3
3
d, JHH = 6.0Hz , CHCH3), 1.32 (9H, d, JHH = 6.0Hz , 3 OCH), 5.63 (1H, s, CH), 7.44–7.95 (5H, m, ArH); 13C NMR
3
CHCH3), 1.40 (3H, t, JHH = 6.0Hz , CH2CH3), 4.35 (2H, s, (75.46MHz, CDCl3): δ (ppm)= 15.48, 21.52, 21.57, 21.73,
3
CH2), 4.69 (2H, q, JHH = 6.0Hz , OCH2), 5.07 (H, sep, 21.78, 60.52, 69.08, 69.53, 70.92, 84.84, 115.37, 127.43,
3 JHH = 6.0Hz , OCH), 5.14 (H, sep, JHH = 6.0Hz , OCH), 129.11, 130.05, 130.85, 151.82, 155.55, 160.61, 162.82,
3
5.54 (1H, s, CH), 7.24–7.35 (5H, m, ArH); 13C NMR 166.07; MS m/z (%) = 459 (M+, 78), 398 (12), 370 (80),
(75.46MHz, CDCl3): δ (ppm) = 15.47, 21.51, 21.55, 21.73, 327 (75), 280 (75), 253 (85), 228 (75), 186 (70), 160 (75),
21.77, 36.38, 60.40, 68.95, 69.45, 70.84, 84.84, 115.30, 127.47, 120 (73), 77 (53), 43 (100), 29 (78); Anal. calcd for
128.79, 128.99, 136.70, 151.92, 156.47, 160.59, 165.92, 166.18; C22H25N3O6S (459.52): C, 57.50; H, 5.48; N, 9.14%. Found:
MS m/z (%) = 473 (M+, 25), 428 (65), 384 (87), 368 (65), 341 C, 57.74; H, 5.42; N, 8.87%.
(73), 284 (85), 266 (100), 241 (80), 200 (78), 173 (68), 148 (65),
Diisopropyl 1-[5-(4-bromophenyl)-1,3,4-thiadia-
116 (58), 83 (92), 66 (90), 43 (83), 29 (70). Anal. calcd for zol-2-yl]-4-ethoxy-5-oxo-2,5-dihydro-1H-pyrrole-2,3-di-
C23H27N3O6S (473.54): C, 58.34; H, 5.75; N, 8.87%. Found: C, carboxylate (5n): pale yellow powder (0.262g, 48%), m.p.
58.52; H, 5.79; N, 8.61%.
163°C–164°C; IR (KBr) (υmax/cm−1): 1752, 1723, 1704 (3
1
Diisopropyl 4-ethoxy-5-oxo-1-[5-(p-tolyl)-1,3,4-thiadia- C=O); H NMR (300.13MHz, CDCl3): δ (ppm) = 1.24
zol-2-yl]-2,5-dihydro-1H-pyrrole-2,3-dicarboxylate (5k): (3H, d, 3 JHH = 6.0Hz , CHCH3), 1.33 (3H, d,
pale yellow powder (0.316g, 67%), m.p. 146°C–148°C; IR 3 JHH = 6.0Hz , CHCH3), 1.34 (6H, d, JHH = 6.0Hz , 2
3
3
(KBr) (υmax/cm−1): 1751, 1725, 1701 (3 C=O); H NMR CHCH3), 1.44 (3H, t, JHH = 6.0Hz , CH2CH3), 4.73 (2H,
1
(300.13MHz,CDCl ):δ(ppm)=1.28(3H,d, 3 JHH = 6.0Hz, q, JHH = 6.0Hz , OCH2), 5.08 (H, sep, JHH = 6.0Hz ,
3
3
3
3
3
CHCH3), 1.36 (3H, d, JHH = 6.0Hz , CHCH3), 1.37 (6H, OCH), 5.16 (H, sep, JHH = 6.0Hz , OCH), 5.62 (1H, s,
3
3
3
d, JHH = 6.0Hz , 2 CHCH3), 1.47 (3H, t, JHH = 6.0Hz , CH), 7.59 (2H, d, JHH = 9.0Hz , 2 CHAr), 7.79 (2H, d,
CH2CH3), 2.43 (3H, s, CH3), 4.78 (2H, q, JHH = 6.0Hz , 3 JHH = 9.0Hz , 2 CHAr); 13C NMR (75.46MHz, CDCl3): δ
3
3
OCH2), 5.12 (H, sep, JHH = 6.0Hz , OCH), 5.19 (H, sep, (ppm)=15.47, 21.52, 21.57, 21.73, 21.78, 60.53, 69.13,
3 JHH = 6.0Hz , OCH), 5.66 (1H, s, CH), 7.30 (2H, d, 69.58, 70.99, 84.84, 115.45, 125.25, 128.75, 128.99,
3 JHH = 9.0Hz , 2 CHAr), 7.85 (2H, d, JHH = 9.0Hz , 2 132.35, 151.72, 155.67, 160.58, 163.18, 166.02; MS m/z
3
CHAr); 13C NMR (75.46MHz, CDCl3): δ (ppm) = 15.54, (%) = 538 (M+, 33), 450 (58), 407 (30), 357 (25), 331
21.51, 21.58, 21.64, 21.79, 21.84, 60.56, 69.12, 69.57, (63), 305 (20), 181 (18), 125 (18), 97 (23), 41 (68), 43
70.96, 115.37, 127.36, 127.41, 129.85, 141.34, 151.93, (100), 28 (88). Anal. calcd for C22H24BrN3O6S (538.41):
155.32, 160.70, 162.83, 164.54, 166.16; MS m/z (%) = 473 C, 49.08; H, 4.49; N, 7.80%. Found: C, 49.32; H, 4.42; N,
(M+, 95), 411 (40), 383 (90), 341 (77), 326 (85), 294 (82), 7.58%.
266 (100), 241 (78), 200 (75), 173 (73), 134 (50), 116 (73),
43 (90). Anal. calcd for C23H27N3O6S (473.54): C, 58.34; H,
5.75; N, 8.87%. Found: C, 58.62; H, 5.70; N, 8.63%.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with
Diisopropyl 4-ethoxy-5-oxo-1-[5-(m-tolyl)-1,3,4-thiadi- respect to the research, authorship, and/or publication of this
article.
azol-2-yl]-2,5-dihydro-1H-pyrrole-2,3-dicarboxylate (5l):
pale yellow powder (0.292g, 61%), m.p. 107°C–108°C;
IR (KBr) (υmax/cm−1): 1732, 1700, 1637 (3 C=O); 1H NMR
Funding
(300.13MHz, CDCl3):
δ
(ppm)
=
1.24 (3H, d, The author(s) disclosed receipt of the following financial support
3
3 JHH = 6.0Hz , CHCH3), 1.33 (3H, d, JHH = 6.0Hz ,
for the research, authorship, and/or publication of this article: The
Research Council of Ferdowsi University of Mashhad is acknowl-
edged for financial support (Grant No. 3/50159).
3
CHCH3), 1.34 (6H, d, JHH = 6.0Hz , 2 CHCH3), 1.44
3
(3H, t, JHH = 6.0Hz , CH2CH3), 2.41 (3H, s, CH3), 4.74
3
3
(2H, q, JHH = 6.0Hz , OCH ), 5.08 (H, sep, JHH = 6.0Hz
, OCH), 5.16 (H, sep, JHH 2= 6.0Hz , OCH), 5.62 (1H, s,
3
ORCID iD
CH), 7.26–7.77 (4H, m, ArH); 13C NMR (75.46MHz,
CDCl3): δ (ppm) = 15.48, 21.28, 21.52, 21.58, 21.73,
21.78, 60.50, 69.07, 69.52, 70.90, 115.33, 124.66, 127.95,
Abbas Ali Esmaeili
https://orcid.org/0000-0002-1650-0224
Supplemental material
129.00, 129.91, 131.66, 138.96, 151.86, 155.45, 160.63, Supplemental material for this article is available online.
162.79, 164.55, 166.09; MS m/z (%) = 473 (M+, 100), 412
References
(5), 385 (100), 341 (60), 326 (85), 294 (67), 267 (100), 241
(45), 173 (15), 116 (18), 43 (100), 29 (82). Anal. calcd for
C23H27N3O6S (473.54): C, 58.34; H, 5.75; N, 8.87%. Found:
C, 58.26; H, 5.71; N, 8.71%.
Diisopropyl 4-ethoxy-5-oxo-1-[5-phenyl-1,3,4-thiadia-
zol-2-yl]-2,5-dihydro-1H-pyrrole-2,3-dicarboxylate (5m):
White powder (0.340g, 72%), m.p. 148°C–149°C; IR
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