Synthesis of novel 1-(benzo[d]thiazol-2-yl)-1H-pyrrol-2(5H)-ones

Article abstract of DOI:10.1002/jhet.1885

The titled products comprising of two mutually merged bioactive nucleuses, 2-aminobenzo[d]thiazole and 2,5-dihydropyrrole rings, were obtained from the reaction between dialkyl acetylenedicarboxylates and alkyl 2-(benzo[d]thiazol-2-yl)amino-2-oxoacetates

Full text of DOI:10.1002/jhet.1885

Month 2014
Synthesis of Novel 1-(Benzo[d]thiazol-2-yl)-1H-pyrrol-2(5H)-ones
a
b,c
Kurosh Rad-Moghadam, Abbas Ali Esmaeili, Saeid Amini Ghalandarabad,b Fereshteh Hoseininejad,b
*
Seyyed Adel Fallah-Rasoulinejad,a and Samaneh Kiania
aChemistry Department, University of Guilan, Rasht, P.O. Box 41335-19141, Iran
bChemistry Department, University of Birjand, Birjand, P.O. Box 97175/615, Iran
cChemistry Department, Ferdowsi University of Mashhad, Mashhad, Iran
*
E-mail: radmm@guilan.ac.ir
Received April 23, 2012
DOI 10.1002/jhet.1885
Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com).
R2O2C
X
X
CO2R2
OR1
S
N
S
NH2
N
N
O
The titled products comprising of two mutually merged bioactive nucleuses, 2-aminobenzo[d]thiazole and
2,5-dihydropyrrole rings, were obtained from the reaction between dialkyl acetylenedicarboxylates and alkyl
2-(benzo[d]thiazol-2-yl)amino-2-oxoacetates in the presence of triphenylphosphine at RT.
J. Heterocyclic Chem., 00, 00 (2014).
INTRODUCTION
with amines [20–22], palladium-catalyzed direct oxidative
cyclization of N-arylthioureas [23], and palladium-catalyzed
amination of 2-halobenzothioureas [24]. All of these
methods have their own merit; however, some suffer from
limits such as requiring harsh conditions or unavailability
of the requisite substrates.
As part of our continuing interest in the development of
new synthetic methods in heterocyclic chemistry [25],
herein, we describe a two-step method planned for the
synthesis of some novel 1-(benzo[d]thiazol-2-yl)-1H-
pyrrol-2(5H)-ones.
1H-Pyrrol-2(5H)-one and 2-aminobenzo[d]thiazole are
two recurrent nucleuses being found in a variety of bioac-
tive molecules. Pyrrolidinone-containing compounds, for
example, have shown to be avb3 antagonists with high
affinity for avb3 receptors [1], potent CDK2 inhibitor
in cellular assays [2], HIV-1 integrase inhibitor [3], HIV
protease inhibitor [4], and inhibitor of influenza virus
neuraminidase [5]. On the other hand, benzothiazole and
2-aminobenzothiazole motifs constitute the core of many
pharmacologically functional compounds including poten-
tial antitumor agents [6], neurotransmission blockers [7],
a4b1 integrin antagonist [8], and valuable inhibitors of
phosphoinositide-3-kinase [9] as well as of human mast
cell tryptases [10]. In addition, there are several reports
addressing distinct pharmacophoric features created from
coupling of benzothiazole and pyrrolidine frameworks.
These compounds were reported as peroxisome prolifera-
tor-activated receptor agonist [11], the H3-receptor ligand
[12], human cytomegalovirus protease [13], and potent
inhibitors of cathepsin K, the main proteolytic enzyme se-
creted by osteoclasts during resorption of bone [14]. The
importance of these compounds can also be evidenced to
several patents issued on their applications. Therefore, it
is not surprise that several routes have been developed
for the synthesis of 1-(2-benzothiazolyl)pyrrolidines includ-
ing the modified Hugerschoff reaction of thiourea substrates
[15–17], condensation of 2-aminobenzothiazoles with
cyclic anhydrides, aromatic nucleophilic substitution of
2-benzothiazolyl halides with amines [18], copper catalyzed
N-benzothiazolylation of amines [19], copper or silver-
catalyzed direct oxidative coupling of simple benzothiazoles
RESULTS AND DISCUSSION
To approach the synthesis of the desired dialkyl
1-(benzo[d]thiazol-2-yl)-4-alkoxy-5-oxo-2,5-dihydro-1H-
pyrrole-2,3-dicarboxylates (5), we started from condensation
of the commercially available 2-aminobenzo[d]thiazoles
(1) with methyl chlorooxylate (2a) to obtain the required
intermediate substrate, ethyl 2-(benzo[d]thiazol-2-yl)
amino-2-oxoacetate (3). This reaction was carried out in
dichloromethane solution wherein the initial product
precipitates once is formed as the hydrochloride salt.
The salt was neutralized in situ, without separation, by
addition of triethylamine and heating until complete
dissolution of the salts. Removal of the solvent by evapo-
ration gave a fairly high yield of the required compound
3. Fortunately, no cyclization-byproduct was formed
via a probable intramolecular amidation of 3 under the
applied neutralization conditions. Synthesis of the final
product was achieved by the subsequent cyclocondensa-
tion reaction that is thought to proceed through an
© 2014 HeteroCorporation

K. Rad-Moghadam, A. A. Esmaeili, S. A. Ghalandarabad,
F. Hoseininejad, S. A. Fallah-Rasoulinejad, and S. Kiani
Vol 000
intramolecular Wittig reaction. In this regard, the obtained
substrate 3 was treated with almost equimolar quantities of
triphenylphosphine and dimethyl acetylenedicarboxylate
at around ꢀ5ꢁC. This final step of synthesis proceeded
smoothly without the aid of any stimulating energy
sources or catalysts to give the product 5a in fairly high
yields (Scheme 1).
It is worthy to note that no byproduct beside 5a was
resolved from the tarry residue by column chromatogra-
phy. Encouraged by this successful trial synthesis, we set
out to explore the generality of this synthetic route by
examining the scope of substrates. As a result, a variety
of substrates were employed in this survey leading to syn-
thesis of several new products that lend credit to viability
of the present route even with substrate variation. Yields
of several products synthesized by this method, as shown
in Table 1, reveal no remarkable trend arising from any de-
pendence on the size of alkyl substituents present at the ester
groups. Nevertheless, presence of an electron-withdrawing
nitro group at 5-position of 2-aminobenzo[d]thiazole (1)
resulted in the lowest yields in this table.
However, we have not studied the mechanism of the
reactions in details; a plausible pathway for the consecutive
events leading to formation of the intermediates and the
products is presented in Scheme 2. It is likely that the
cascade of reactions is triggered by the Michael-addition
of triphenylphosphine on acetylenic ester, resulting in
formation of a zwitterionic adduct [26] which by remov-
ing the amidic proton of the substrate 3 turns into a more
electrophilic phosphonium species and leave the conjugate
base of the amide aside 6. Subsequent conjugate addition
of the anionic amide onto phosphonium cation gives
the key phosphorane ylide 7 that is prone to follow an
intramolecular Wittig reaction to produce the final prod-
uct. On the basis of this proposal, one may reasonably
Scheme 1. The sequence of reactions leading to synthesis of the product.
5a.
O
O
Et3N
Heat
S
N
S
N
OR1
Cl
R1O
NH2
N
+
H
O
O
1
2
3
Ph3P / CH2Cl2 RT
CO2CH3
H3CO2C
4
H3COOC
S
COOCH3
OR1
N
R1 = Me
5a
N
O
Table 1
Syntheses of 1-(benzo[d]thiazol-2-yl)-4-alkoxy-5-oxo-2,5-dihydro-1H-pyrrole-2,3-dicarboxylates (5) from reaction of alkyl 2-(benzo[d]thiazol-2-yl)
amino-2-oxoacetate (3) and dialkylacetylene dicarboxylate (4).
Yield (%)a
R2
R1
X
Product
74
88
78
84
90
98
69
67
61
86
81
57
53
Me
Et
Me
Me
Me
Me
Me
Et
Et
Et
Et
Et
H
H
H
H
H
H
H
H
H
Me
Me
NO2
NO2
5a
5b
5c
5d
5e
5f
5g
5h
5i
i-Pr
t-Bu
Neopentyl
i-Pr
Me
Et
t-Bu
Me
5j
5k
5l
Et
Me
Et
Et
Et
Et
5m
aIsolated yields.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
Synthesis of Novel 1-(Benzo[d]thiazol-2-yl)-1H-pyrrol-2(5H)-ones
Scheme 2. A proposed mechanism for the formation of products 5.
Ph3P
R2O2C
R2O2C
Ph3P
CO2R2
R2O2C
Ph3P
CO2R2
CO2R2
4
6
O
O
H
S
S
N
N
OR1
OR1
N
N
O
O
X
X
X
3
CO2R2
R2OOC
COOR2
OR1
R2OOC
S
PPh3
O
S
- Ph3P=O
N
N
N
N
OR1
O
O
X
5
7
ascribe the success of this synthetic method to the acidity
of the amidic proton of the substrate 3 and in turn to the
electron-withdrawing effect of benzo[d]thiazole ring.
However, the electron-withdrawing effect of the benzo
[d]thiazole ring is not too extensive to make the preparation
of amide (3) difficult.
heterocyclic framework, providing the synthesis of novel
dialkyl 1-(benzo[d]thiazol-2-yl)-4-alkoxy-5-oxo-2,5-dihydro-
1H-pyrrole-2,3-dicarboxylates. The efficiency of these
syntheses might be attributed to the moderate electron-
withdrawing effect of benzo[d]thiazole ring making its
2-amido-substituent acidic enough to proceed the intramo-
lecular Wittig reaction, whereas do not prevent the precur-
sor’s 2-amino group from being sufficiently nucleophilic
to undergo acylation with alkyl chlorooxylates.
Structures of all the products are well consistent with
1
their IR, H-NMR, 13C-NMR, and mass spectral data as
well as elemental microanalyses. The mass spectrum of
5a, for example, displayed the molecular ion peak at
m/z = 375, which is consistent with the 1:1 adduct of
dimethyl acetylenedicarboxylate and the substrate 3 associ-
ated with loss of a water molecule. The IR spectrum of this
compound exhibited well defined absorptions in harmony
with its characteristic vibrations. Of notable are three
absorption bands arising from the nonconjugated ester
group at 1740 cmꢀ1, the conjugated ester group at
1690 cmꢀ1, and the g-lactam carbonyl at 1725 cmꢀ1. There
are two strong and characteristic bands centered at 1440
and 1350 cmꢀ1 in IR spectra of all the products, attribut-
able to the typical vibrations of pyrrol-2(5H)-one ring.
EXPERIMENTAL
General. All of the solvents and reagents were purchased
from Fluka (Buchs, Switzerland) or Merck (Darmstadt,
Germany) chemical companies. Progress of the reactions were
monitored by chromatography using silica gel-coated aluminum
sheets using 1:1 mixture of petroleum ether and ethyl acetate as
eluents. Melting points were measured on an Electrothermal
apparatus and are uncorrected. IR spectra were obtained in KBr
disks on a Shimadzu IR-470 spectrometer (Kyoto, Japan). 1H-
NMR and 13C-NMR spectra were measured with Bruker
(Karlsruhe, Germany) DRX AVANCE spectrometers. Chemical
shifts of 1H-NMR and 13C-NMR spectra were expressed in
parts per million downfield from TMS. Mass spectra were
recorded on a (Kyoto, Japan) QP1100EX mass spectrometer
operating at an ionization potential of 70 eV. Elemental analyses
for C, H, and N were performed using a Foss Heraus (Hanau,
1
The H-NMR spectrum of this product displayed three
sharp lines readily recognized as arising from three meth-
oxy groups. There was observed also a fairly sharp singlet
for the allylic proton of the pyrrol-2(5H)-one ring along
with four characteristic signals of appropriate chemical
shifts and coupling constants for the four aromatic
protons. The 13C{1H}NMR spectrum of 5a showed 17
distinct resonances in agreement with the proposed structure.
Partial assignments of these resonances are suggested in the
Experimental section.
Germany) CHN-O-rapid analyzer.
Typical preparation of ethyl 2-(benzo[d]thiazol-2-yl)amino-
2-oxoacetate (3a).
To a 25-mL round-bottomed flask
containing a magnetic stirring bar and a solution of 0.136 g
ethyl chlorooxylate (1 mmol) in 5 mL dichloromethane was
added dropwise and under stirring a solution of 0.150 g
(1 mmol) 2-aminobenzothiazole in 10 mL dichloromethane over
10 min. The white solids appeared immediately after addition
was dissolved by heating the mixture up to 40ꢁC and addition
of triethylamine until achieving a clear solution. At this
instance, a yellow solution is obtained, which was stirred for
6 h. To workup the reaction, the solvent was evaporated
under vaccuo, and the remaining solid was recrystallized from
ethanol (95.5%).
CONCLUSION
In conclusion, a two-step route was devised to merge
the two biologically important nucleuses, 2-aminobenzo
[d]thiazole and 1H-pyrrol-2(5H)-one, into an elaborated
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

K. Rad-Moghadam, A. A. Esmaeili, S. A. Ghalandarabad,
F. Hoseininejad, S. A. Fallah-Rasoulinejad, and S. Kiani
Vol 000
Typical synthesis of compound 5a. To a stirred solution of
ethyl 2-(benzo[d]thiazol-2-yl)amino-2-oxoacetate (3a) 0.250 g
(1 mmol) and triphenylphosphine 0.314 g (1.2 mmol) in 10 mL
dichloromethane at ꢀ12ꢁC was added dropwise a solution of
dimethyl acetylenedicarboxylate 0.170 g (1.2 mmol) in 2 mL
dichloromethane over 10 min. The reaction mixture was stirred
further overnight, and the product was separated by column
chromatography on silica gel (230–400 mesh) support using
petroleum ether and ethyl acetate (1:1) as eluents. The separated
product was recrystallized from ethanol (95.5%) to give 0.26 g
(69%) of the product dimethyl 1-(benzo[d]thiazol-2-yl)-4-
methoxy-5-oxo-2,5-dihydro-1H-pyrrole-2,3-dicarboxylate (5a),
(14), 202 (30), 174 (17), 161 (22), 134 (13), 43 (100).
Anal. Calcd for C20H22N2O6S: C, 57.40; H, 5.30; N, 6.69.
Found: C, 57.33; H, 5.32; N, 6.74.
Di-tert-butyl 1-(1,3-benzo[d]thiazol-2-yl)-4-methoxy-5-oxo-
2,5-dihydro-1H-pyrrole-2,3-dicarboxylate (5d).
White solid,
yield (0.37g) 84%. mp 144–147ꢁC; IR (potassium bromide):
3050, 2950 (C—H str.), 1740, 1725, and 1690 (C═O), 1640,
1520, 1425, 1355 (3-pyrrolin-2-one ring) cmꢀ1
.
1H-NMR
(300.13 MHz, deuterated chloroform): dH 7.80 (2H, t, J = 7.4 Hz,
40-H and 70-H), 7.42 (1H, t, J= 7.4 Hz), 7.31 (1H, m), 5.47 (1H, s,
2-H), 4.34 (OMe), 1.56 (9H, s, C(CH3)3), 1.40 (9H, s, C(CH3)3).
13C-NMR (75.48 MHz, deuterated chloroform): dC 165.53, 163.31,
160.35 (3 C═O), 154.95, 152.26, 148.35 (C-20, C-4, C-30a),
132.18, 126.34, 124.33, 121.57, 121.46, 116.14 (C-3), 83.24
and 82.98 (2 OC(CH3)3), 61.54 (OCH3), 60.15 (C-2), 28.11,
27.74 (2 C(CH3)3); MS (EI) m/z (%): 446 (M+, 1), 346 (2),
290 (14), 202 (10), 167 (16), 149 (62),56 (100). Anal. Calcd
for C22H26N2O6S: C, 59.18; H, 5.87; N, 6.27. Found: C,
mp 103–105ꢁC.
Dimethyl 1-(1,3-benzo[d]thiazol-2-yl)-4-methoxy-5-oxo-2,5-
dihydro-1H-pyrrol-2,3-dicarboxylate (5a). White solid, yield
(0.27 g) 74%. mp 179.5–182ꢁC; IR (potassium bromide): 3050,
2950 (C—H str.) 1690, 1725, and 1740 (C═O), 1630, 1520,
1350, 1440 (3-pyrrolin-2-one ring) cmꢀ1. 1H-NMR (300.13MHz,
deuterated chloroform): dH 7.81 (2H, d, J = 8.1 Hz, 40-H and 70-
H), 7.43 (1H, m), 7.30 (1H, m), 5.61 (1H, s, 2-H), 4.39 (3H, s,
OCH3), 3.85 (3H, s, OCH3), 3.80 (3H, s, OCH3). 13C-NMR
(75.48 MHz, deuterated chloroform): dC 167.67, 162.85,
161.61 (3 C═O), 154.70, 153.07, 148.35 (C-20, C-4, C-30a),
132.11, 126.37, 124.51, 121.93, 121.42, 113.78 (C-3), 60.36,
60.07 (C-2 and OCH3), 53.40, 52.36 (2 OCH3). MS (EI) m/z
(%): 362 (M+, 5), 364 (8), 303 (97), 275 (65), 229 (50), 134
(16). Anal. Calcd for C16H14N2O6S: C, 53.03; H, 3.89; N, 7.73.
59.16; H, 5.91; N, 6.22.
Bis-2,2-dimethylpropyl 1-(1,3-benzo[d]thiazol-2-yl)-4-methoxy-
5-oxo-2,5-dihydro-1H-pyrrole-2,3-dicarboxylate (5e).
White
solid, yield (0.43 g) 90%. mp 161–164ꢁC; IR (potassium
bromide): 3050, 2950 (C—H str.), 1737, 1725, and 1692
(C═O), 1640, 1520, 1430, 1355 (3-pyrrolin-2-one ring) cmꢀ1
.
1H-NMR (300.13 MHz, deuterated chloroform): dH 7.89 (2H,
t, J = 8.8 Hz, 40-H and 70-H), 7.43 (1H, t, J = 7.3 Hz), 7.31
(1H, m), 5.70 (1H, s, 2-H), 4.40 (OMe), 3.76–4.02 (4H, m,
2 OCH2), 4.78 (2H, q, J = 7.0 Hz, OCH2CH3), 1.44 (3H, t,
J = 7.0 Hz, OCH2CH3), 1.02 (9H, s, C(CH3)3), 0.90 (9H, s,
C(CH3)3). 13C-NMR (75.48 MHz, deuterated chloroform): dC
166.89, 163.14, 161.46 (3 C═O), 154.72, 153.03, 148.38
(C-20, C-4, C-30a), 132.16, 126.36, 124.44, 121.85, 121.42,
114.97 (C-3), 75.56 and 74.84 (2 OCH2), 60.30 (OCH3),
60.16 (C-2), 31.65, 31.54 (2 C(CH3)3), 26.48, 26.30 (2 C
(CH3)3). MS (EI) m/z (%): 474 (M+, 1), 360 (3), 279 (5),
167 (24), 149 (100), 112 (13). Anal. Calcd for
C24H30N2O6S: C, 60.74; H, 6.37; N, 5.90. Found: C, 60.70;
Found: C, 53.18; H, 4.02; N, 7.69.
Diethyl 1-(1,3-benzo[d]thiazol-2-yl)-4-methoxy-5-oxo-2,5-
dihydro-1H-pyrrol-2,3-dicarboxylate (5b).
White crystals,
yield (0.34g) 88%. mp 119–121ꢁC; IR (potassium bromide):
3050, 2950 (C—H str.), 1740, 1722, 1690 (C═O), 1640, 1520,
1440, 1375 (3-pyrrolin-2-one ring) cmꢀ1 1H-NMR (300.13
.
MHz, deuterated chloroform): dH 7.85 (1H, d, J = 8.4 Hz),
7.83 (1H, d, J = 8.7 Hz), 7.40 (1H, t, J = 7.3 Hz), 7.29 (1H, t,
J = 7.8 Hz), 5.59 (1H, s, 2-H), 4.36 (3H, S, OCH3), 4.17–4.32
(4H, m, 2 OCH2), 1.34 (3H, t, J = 7.1 Hz CH3), 1.25 (3H, t,
J = 7.1 Hz CH3). 13C-NMR (75.48MHz, deuterated chloroform):
dC 167.14, 162.94, 161.02 (C═O), 154.79, 153.08, 148.32
(C-20, C-30a, C-4), 132.14, 126.34, 124.42, 121.74, 121.43,
114.04 (C-3), 62.41, 61.45, 60.45, 60.34 (2OCH2, C-2 and
OCH2) 14.09, 14.03 (2CH3). MS (EI) m/z (%): 390 (M+, 2),
317 (3), 279 (4), 167 (30), 149 (100), 112 (17), 70 (54), 57
(52), 43 (95), 40 (65). Anal. Calcd for C18H18N2O6S: C, 55.38;
H, 6.44; N, 5.91.
Diisopropyl 1-(1,3-benzo[d]thiazol-2-yl)-4-ethoxy-5-oxo-2,5-
dihydro-1H-pyrrole-2,3-dicarboxylate (5f).
White solid, yield
(0.35 g) 97.5%. mp 114–116ꢁC; IR (potassium bromide):
3050, 2950 (C—H str.), 1738, 1722, and 1687 (C═O), 1630,
1520, 1430, 1360 (3-pyrrolin-2-one ring) cmꢀ1 1H-NMR
.
(300.13 MHz, deuterated chloroform): dH 7.79 (2H, t, J = 8.4 Hz,
40-H and 70-H), 7.30 (1H, m), 7.42 (1H, m), 7.30 (1H, m), 5.59
(1H, s, 2-H), 5.10–5.18 (2H, 2 sep., J=6.3Hz, OCH(CH3)2), 4.78
(2H, q, J=7.0Hz, OCH2CH3), 1.44 (3H, t, J=7.0Hz, OCH2CH3),
1.30–1.34 (9H, m, CH(CH3)2), 1.21 (3H, d, J = 6.3 Hz, CH
(CH3)2). 13C-NMR (75.48MHz, deuterated chloroform): dC
166.68, 163.32, 160.75 (3 C═O), 154.93, 152.62, 148.32 (C-20,
C-4, C-30a), 132.17, 126.34, 124.37, 121.63, 121.45, 113.78
(C-3), 70.41 (OCH2CH3), 69.32, 69.03 (2 OCH ester), 60.64
(C-2), 21.79, 21.83 (2 CH3 of OCH(CH3)2)‚ 21.53, 21.57 (2
CH3 of OCH(CH3)2)‚ 15.58 (OCH2CH3). MS (EI) m/z (%):
432 (M+, 1.37), 272 (14), 230 (48), 167 (38), 149 (38). Anal.
Calcd for C21H24N2O6S: C, 58.32; H, 5.59; N, 6.48. Found: C,
H, 4.65; N, 7.18. Found: C, 55.49; H, 4.73; N, 7.11.
Diisopropyl 1-(1,3-benzo[d]thiazol-2-yl)-4-methoxy-5-oxo-
2,5-dihydro-1H-pyrrol-2,3-dicarboxylate (5c). White solid,
yield (0.33 g) 78%. mp 139–141ꢁC; IR (potassium bromide):
3040, 2950 (C—H str.), 1738, 1723, and 1688 (C═O), 1630,
1520, 1430, 1370 (3-pyrrolin-2-one ring) cmꢀ1 1H-NMR
.
(300.13 MHz, deuterated chloroform): dH 7.80 (2H, t, J = 8.5 Hz,
40-H and 70-H), 7.42 (1H, t, J = 8.5 Hz), 7.30 (1H, m), 5.58 (1H,
s, 2-H), 5.04–5.27 (2H, 2 sep., J = 6.2 Hz, 2 OCH(CH3)2), 4.37
(3H, s, OCH3), 1.30–1.35 (9H, m, 2 CH(CH3)2), 1.21 (3H,
d, J = 6.3 Hz, CH(CH3)2). 13C-NMR (75.48 MHz, deuterated
chloroform): dC 166.58, 163.12, 160.64 (3 C═O), 154.87,
152.95, 148.31 (C-20, C-4, C-30a), 132.18, 126.36, 124.40,
121.64, 121.47, 114.55 (C-3), 70.47, 69.47 (2 OCH), 60.62
(OCH3), 60.48 (C-2), 21.82, 21.77 (2 CH3 of OCH(CH3)2)‚
21.55, 21.58 (2 CH3 of OCH(CH3)2); MS (EI) m/z (%):
418 (M+, 8), 359 (3), 332 (15), 289 (24), 273 (16), 229
58.29; H, 5.67; N, 6.44.
Dimethyl 1-(benzo[d]thiazol-2-yl)-4-ethoxy-5-oxo-2,5-dihydro-
1H-pyrrole-2,3-dicarboxylate (5g).
White crystals, yield
(0.26 g) 69%. mp 103–105ꢁC; IR (potassium bromide): 3050,
2950 (C—H str.) 1689, 1724, and 1736 (C═O), 1630, 1520,
1350, 1440 (3-pyrrolin-2-one ring) cmꢀ1. H-NMR (500.13 MHz,
1
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
Synthesis of Novel 1-(Benzo[d]thiazol-2-yl)-1H-pyrrol-2(5H)-ones
deuterated chloroform): dH 7.84 (2H, d, J = 8.2 Hz, 40-H and
70-H), 7.45 (1H, t, J = 7.6 Hz), 7.34 (1H, t, J = 7.9 Hz), 5.66
(1H, s, 2-H), 4.83 (2H, q, J = 7.0 Hz, OCH2), 3.88 (3H, s,
OCH3), 3.82 (3H, s, OCH3), 1.48 (3H, t, J = 7.0 Hz, CH3).
13C-NMR (125.77 MHz, deuterated chloroform): dC 168.17,
163.45, and 162.15 (3 C═O), 155.22, 153.29, 148.82 (C-20,
C-4, C-30a), 132.57, 126.77, 124.90, 122.35, 121.83, 114.61
(C-3), 69.51, 60.57 (C-2 and OCH2), 53.79, 52.69 (2 OCH3),
16.08 (CH3). MS (EI) m/z (%): 375 (M+, 5), 279 (22.1), 167
(64), 149 (100), 57 (46), 29 (10). Anal. Calcd for
C17H16N2O6S: C, 54.25; H, 4.28; N, 7.44. Found: C, 54.19; H,
69.08 (C-2), 60.13 (4-OCH2), 53.39, 52.29 (2 CO2CH3),
21.51 (60-CH3), 15.70 (OCH2CH3); MS (EI) m/z (%): 390
(M+, 100), 375 (M+ —CH3, 12), 323 (20), 333 (25), 289
(22), 271 (42), 243 (40), 175 (47). Anal. Calcd for
C18H18N2O6S: C, 55.38; H, 4.65; N, 7.18. Found: C, 55.27;
H, 4.62; N, 7.19.
Diethyl 1-(6-methylbenzo[d]thiazol-2-yl)-4-ethoxy-5-oxo-2,5-
dihydro-1H-pyrrole-2,3-dicarboxylate (5k).
Pale yellow
powder, yield (0.339 g) 81%. mp 100–102ꢁC; IR (potassium
bromide): 3054, 29 (C—H str.), 1743, 1722, 1694 (C═O), 1627
(C═C str.), 1519, 1440, 1364 (3-pyrrolin-2-one ring),
1190 cmꢀ1 1H-NMR (400 MHz, deuterated chloroform): dH
.
4.39; N, 7.40.
Diethyl 1-(benzo[d]thiazol-2-yl)-4-ethoxy-5-oxo-2,5-dihydro-
7.70 (1H, d, J = 8.4 Hz, 40-H), 7.63 (1H, s, 70-H), 7.26 (1H, dd,
J = 8.4 and 1.2 Hz, 50-H), 5.63 (1H, s, 2-H), 4.82 (2H, q,
J = 7.2 Hz, 3-OCH2CH3), 4.35–4.24 (4H, m, 2 CO2CH2CH3),
1.47 (3H, t, J = 7.2 Hz, CH3), 1.37 (3H, t, J = 7.2 Hz, CH3), 1.29
(3H, t, J = 7.2 Hz, CH3). 13C-NMR (100 MHz, deuterated
chloroform): dC 167.26, 163.10, 161.21, 154.10, 152.95
(3 C═O, C-20 and C-4), 146.35 (C-30a), 134.54, 132.34 (C-60
and C-70a), 127.84, 121.33, 121.20 (C-40, C-50 and C-70),
114.36 (C-3), 69.10 (C-2), 62.40, 61.36, 60.41 (3 O—CH2),
21.50 (60-CH3), 15.63, 14.10, 14.04 (3 OCH2CH3); 418 (M+,
100), 345 (19), 289 (59), 271 (68), 243 (48), 175 (64). Anal.
Calcd for C20H22N2O6S: C, 57.40; H, 5.30; N, 6.69. Found:
1H-pyrrole-2,3-dicarboxylate (5h).
White crystals, yield
(0.27 g) 67%. mp 90–93ꢁC. IR (potassium bromide): 3050,
2980 (C—H str.), 1740, 1722 (C═O), 1636, 1518, 1442
(3-pyrrolin-2-one ring), 1375 cmꢀ1
.
1H-NMR (500.13 MHz,
deuterated chloroform): dH 7.85 (1H, d, J = 8.4 Hz), 7.83 (1H, d,
J = 8.7 Hz), 7.46 (1H, t, J = 7.9 Hz), 7.35 (1H, t, J = 7.6 Hz), 5.66
(1H, s, 2-H), 4.83 (2H, q, J = 7.0 Hz, 4-OCH2), 4.37–4.32 (3H,
m, OCH2), 4.27–4.24 (1H, m, OCH2), 1.48 (3H, t, J = 7.0 Hz
CH3), 1.39 (3H, t, J = 7.1 Hz CH3), 1.31 (3H, t, J = 7.1 Hz,
CH3). 13C-NMR (125.77 MHz, deuterated chloroform): dC
167.63, 163.61, 161.60 (C═O), 155.32, 153.26, 148.82 (C-20,
C-30a, C-4), 132.63, 126.76, 124.84, 122.20, 121.68, 114.96
(C-3), 69.55, 62.83, 61.79, 60.85 (C-2 and 3OCH2) 16.03,
14.51, 14.46 (3CH3). MS (EI) m/z (%): 404 (M+, 6), 257 (54),
125 (50), 84 (47), 57 (100), 43 (71), 29 (11). Anal. Calcd for
C19H20N2O6S: C, 56.42; H, 4.98; N, 6.93. Found: C, 56.47; H,
C, 57.38; H, 5.35; N, 6.63.
Dimethyl 1-(6-nitrobenzo[d]thiazol-2-yl)-4-ethoxy-5-oxo-2,5-
dihydro-1H-pyrrole-2,3-dicarboxylate (5l).
Creamy powder,
yield (0.240 g) 57%. mp 172–174ꢁC; IR (potassium bromide):
3089, 2948 (C—H str.), 1736, 1717 (C═O), 1638 (C═C str.),
1520, 1505, 1442, 1337 (NO2), 1217 cmꢀ1
.
1H-NMR
5.07; N, 7.78.
Di-tert-butyl 1-(benzo[d]thiazol-2-yl)-4-ethoxy-5-oxo-2,5-
(400 MHz, deuterated chloroform): dH 8.78 (1H, d, J = 2.4 Hz,
70-H), 8.35 (1H, dd, J = 8.8 and 2.0 Hz, 50-H), 7.90 (1H, d,
J = 8.8 Hz, 40-H), 5.67 (1H, s, 2-H), 4.83 (2H, q, J = 7.2 Hz,
3-OCH2CH3), 3.90 (3H, s, OCH3), 3.85 (3H, s, OCH3), 1.49
(3H, t, J = 7.2 Hz, 3-OCH2CH3). 13C-NMR (100 MHz, deuterated
chloroform): dC 167.36, 163.45, 161.58, 159.05, 152.80,
152.32 (3 C═O, C-4, C-20, C-60), 144.37, 132.57 (C-30a and
C-70a), 122.16, 121.94, 118.19 (C-40, C-50, and C-70), 114.86
(C-3), 69.35 (C-2), 60.20 (3-OCH2), 53.61, 52.49 (2 OCH3),
15.65 (OCH2CH3); 421 (M+, 100), 405 (40), 362 (31), 320
(38), 302 (61), 274 (85), 205 (54). Anal. Calcd for
C17H15N3O8S: C, 48.46; H, 3.59; N, 9.97. Found: C, 48.37; H,
dihydro-1H-pyrrole-2,3-dicarboxylate (5i).
White powder,
yield (0.28g) 61%. mp 120–122ꢁC; IR (potassium bromide):
3072, 2990 (C—H str.), 1739, 1717, 1700 (C═O), 1630, 1520,
1440, 1363 (3-pyrrolin-2-one ring), 1260 cmꢀ1
.
1H-NMR
(500.13 MHz, deuterated chloroform): dH 7.84 (2H, t, J=7.4Hz,
40-H and 70-H), 7.46 (1H, t, J = 7.5 Hz), 7.34 (1H, t,
J = 7.8 Hz), 5.52 (1H, s, 2-H), 4.81–4.76 (2H, m, —OCH2),
1.60 (9H, s, C(CH3)3), 1.48 (3H, t, J = 7.0 Hz, OCH2CH3),
1.44 (9H, s, C(CH3)3). 13C-NMR (125.77 MHz, deuterated
chloroform): dC 166.06, 164.01, and 160.84 (3 C═O), 155.47,
152.30, 148.85 (C-20, C-30a, C-4), 132.66, 126.73, 124.71,
122.01, 121.86, 117.23 (C-3), 83.57, 83.18 (2 OC(CH3)3),
69.08, 62.04 (C-2 and OCH2), 28.56, 28.18 (2 C(CH3)3),
16.01 (OCH2CH3); MS (EI) m/z (%): 460 (M+, 14.1), 360
(47), 304 (95), 257 (18), 161 (34), 57 (100). Anal. Calcd for
C23H28N2O6S: C, 59.98; H, 6.13; N, 6.08. Found: C, 60.06; H,
3.56; N, 10.12.
Diethyl 1-(6-nitrobenzo[d]thiazol-2-yl)-4-ethoxy-5-oxo-2,5-
dihydro-1H-pyrrole-2,3-dicarboxylate (5m). Creamy powder,
yield (0.238 g) 53%. mp 170–172ꢁC; IR (potassium bromide):
3100, 2997 (C—H str.), 1739, 1718 (C═O), 1632 (C═C
str.), 1507, 1440, 1338 (NO2), 1200 cmꢀ1
.
1H-NMR
6.18; N, 6.01.
Dimethyl 1-(6-methylbenzo[d]thiazol-2-yl)-4-ethoxy-5-oxo-2,5-
(400 MHz, deuterated chloroform): dH 8.79 (1H, d,
J = 2.2 Hz, 70-H), 8.35 (1H, dd, J = 8.8 and 2.2 Hz, 50-H),
7.88 (1H, d, J = 9.2 Hz, 40-H), 5.66 (1H, s, 2-H), 4.81 (2H, q,
J = 6.8 Hz, 3-OCH2CH3), 4.38–4.25 (4H, m, 2 CO2CH2CH3),
1.49 (3H, t, J = 6.8 Hz, CH3), 1.39 (3H, t, J = 6.8 Hz, CH3),
1.32 (3H, t, J = 6.8 Hz, CH3). 13C-NMR (100 MHz, deuterated
chloroform): dC 166.81, 163.60, 161.02, 159.16, 152.80,
152.24 (3 C═O, C-4, C-20, C-60), 144.34, 132.61 (C-30a and
C-70a), 122.18, 121.75, 118.23 (C-40, C-50, and C-70), 115.22
(C-3), 69.38 (C-2), 62.70, 61.64, 60.49 (3 OCH2), 15.58 (CH3),
14.09 (CH3), 14.06 (CH3); 449 (M+, 36), 377 (43), 348 (34),
320 (68), 302 (73), 274 (100), 206 (69). Anal. Calcd for
C19H19N3O8S: C, 50.78; H, 4.26; N, 9.35. Found: C, 50.80; H,
4.34; N, 9.23.
dihydro-1H-pyrrole-2,3-dicarboxylate (5j).
White powder,
yield (0.336g) 86%. mp 150–152ꢁC; IR (potassium bromide):
3060, 2950 (C—H str.), 1737, 1711 (C═O), 1633, 1521, 1438,
1360 (3-pyrrolin-2-one ring), 1233, 1200 cmꢀ1
.
1H-NMR
(400 MHz, deuterated chloroform): dH 7.72 (1H, d, J = 8.0Hz,
40-H), 7.64 (1H, d, J = 2.0 Hz, 70-H), 7.27 (1H, dd, J = 8.0
and 2.0 Hz, 50-H), 5.65 (1H, s, H-2), 4.85 (2H, q, J = 7.0 Hz,
4-OCH2—CH3), 3.88 (3H, s, CO2CH3), 3.82 (3H, s,
CO2CH3), 2.49 (3H, s, 60-CH3), 1.48 (3H, t, J = 7.0 Hz, 4-
OCH2CH3). 13C-NMR (100 MHz, deuterated chloroform): dC
167.80, 162.96, 161.78, 154.00, 153.00 (3 C═O, C-20 and
C-4), 146.37 (C-30a), 134.63, 132.29 (C-60 and C-70a),
127.86, 121.50, 121.17 (C-40, C-50, and C-70), 114.01 (C-3),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

K. Rad-Moghadam, A. A. Esmaeili, S. A. Ghalandarabad,
F. Hoseininejad, S. A. Fallah-Rasoulinejad, and S. Kiani
Vol 000
Acknowledgments. Authors would like to thank the research
councils of University of Guilan and University of Birjand for
financial support of this work.
A.; Abraham, W. M.; Recacha, R.; Chattopadhyay, D.; Maryanoff, B. E.
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DOI 10.1002/jhet