Heteropolyacid catalyzed formation of thioparabanic acid derivatives

Article abstract of DOI:10.1007/s00706-016-1774-y

Abstract: A heteropoly acid-catalyzed reaction between amines, ammonium thiocyanate, and oxalate esters is reported. This route turned out to be a useful method for the preparation of thioparabanic acid derivatives. Graphical abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s00706-016-1774-y

Monatsh Chem
DOI 10.1007/s00706-016-1774-y
ORIGINAL PAPER
Heteropolyacid catalyzed formation of thioparabanic acid
derivatives
Alireza Samzadeh-Kermani1
Received: 14 February 2016 / Accepted: 10 May 2016
Ó Springer-Verlag Wien 2016
Abstract A heteropoly acid-catalyzed reaction between
amines, ammonium thiocyanate, and oxalate esters is
reported. This route turned out to be a useful method for
the preparation of thioparabanic acid derivatives.
Graphical abstract
multicomponent reactions, has shown increasing popularity
[5–8]. Additionally, transition metal-catalyzed multicom-
ponent reactions have served as powerful tools for the rapid
and efficient synthesis of heterocyclic compounds [9–12].
These strategies are used to minimize problems with
classical multicomponent reactions, such as regioselectiv-
ity, low yields, and competing side reactivities. Among the
various catalysts, heteropolyacids (HPAs) have been
broadly used as acidic catalysts in multicomponent reac-
tions [13]. HPAs are strong bronsted acids and structural
characterization of the HPA proton sites is an important
step toward understanding the catalytic activity. These
studies are very well recapitulated in a review written by
Kozhevnikov [14].
O
O
R1
S
N
R2
H3PW12O40
O
R2
R1 NH2 + NH4SCN +
R1: Alkyl and aryl
NH
i-PrOH, 85 °C
O
17 Examples
29-98% Yields
2-Thioxo-4,5-imidazolidinedione derivatives (thiopara-
banic acids) are key scaffold in medicines those broadly
used as: antiviral [15], anticancer [16], aldose reductase
inhibitors [17], potassium channel openers [18], antibac-
terial [19], and usefulness in treating atherosclerosis [20].
There are many efficient methods for the synthesis of this
important class of heterocycle, but most of the various
approaches have certain restrictions regarding the scope
and placement of the substitution pattern around the hete-
rocycle core [21–25]. In accordance with our interest at the
synthesis of heterocyclic compounds [26–29], we exam-
ined the efficiency of heteropolyacids for the synthesis of
functionalized thioparabanic acids using oxalate esters,
amines, and thiocyanate precursors.
Keywords Thioparabanic acid Á Heteropoly acid Á
Oxalate ester Á Amine Á Catalytic-multicomponent reaction
Introduction
Heterocyclic compounds are ubiquitously found in modern
society as pharmaceutical agents and bioactive compounds
[1–4]. For this reason, synthetic chemists continue to be
interested in the construction and functionalization of
heterocyclic cores. Among the various strategies available,
Electronic supplementary material The online version of this
article (doi:10.1007/s00706-016-1774-y) contains supplementary
material, which is available to authorized users.
& Alireza Samzadeh-Kermani
drsamzadeh@gmail.com;
arsamzadeh@uoz.ac.ir
Results and discussion
The reaction was initially examined using n-butyl amine
(1a), ammonium thiocyanate (2a), and dimethyl oxalate
(3a) in the presence of H3PW12O40 as the solid acid.
1
Chemistry Department, Faculty of Science, University of
Zabol, Zabol, Iran
123

A. Samzadeh-Kermani
Stirring in MeCN at 85 °C for 8 h afforded 1-butyl-2-
thioxoimidazolidine-4,5-dione (4a) in 41 % yield together
with 3-butylthiazolidine-2,4,5-trione (5) in 9 % yield. To
develop the reaction conditions a variety of solvents, cat-
alysts, and thiocyanate precursors were examined
(Table 1). No desired product formation occurred without
the catalyst even at higher temperature (Table 1, entry 1).
Additionally, catalyst screen showed that HPA’s with of
tungsten resulted in higher yields than those composed of
molybdenum, most likely due to the greater acidity of
tungsten containing HPA (Table 1, entries 2–6) [30].
Reaction conducted with Cs-containing HPA occurred to
low conversion (Table 1, entry 7). Supported H3PW12O40
(Fig. 1) on amorphous silica required longer reaction times
to afford the desired product in acceptable yield (Table 1,
entry 8). Trifluoroacetic acid and trifluoromethanesulfonic
acid also promoted the reaction in good yields. However,
common bronsted acids like HCl and H2SO4 were not
Table 1 Optimization of reaction conditions
O
Bu
N
O
NH
4a
S
O
Solvent
Catalyst
OEt
and/or
+
+
EtO
n-Bu NH2
MSCN
O
O
Bu
1a
2
3a
N
O
S
5
O
Entry
Catalyst
2
M
Solvent
Yield of 4/%
1
2
3
4
5
6
7
8
–
2a
2a
2a
2a
2a
2a
2a
2a
NH4
NH4
NH4
NH4
NH4
NH4
NH4
NH4
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
–
H3PW12O40
H4SiW12O40
93
72
50
69
26
17
89a
H4PMo12O40
.
H3PMo10W2O40
H4SiMo12O40
Cs2HPW12O40
H3PW12O40
Silica
-
9
H3PW12O40
H3PW12O40
H3PW12O40
H3PW12O40
H3PW12O40
H3PW12O40
H3PW12O40
H3PW12O40
H3PW12O40
H3PW12O40
H3PW12O40
2a
2a
2a
2a
2a
2a
2b
2c
2d
2e
2a
NH4
NH4
NH4
NH4
NH4
NH4
K
DMSO
EtOH
54
78
39
4
10
11
12
13
14
15
16
17
18
19
DMF
Toluene
MeCN
H2O
,
,
41
39
62
75
90
–
i-PrOH
i-PrOH
i-PrOH
i-PrOH
MeCN
Ag
Li
Fe(II)
K
61b
For all entries except stated otherwise: 1a (1.0 mmol), 2 (1.5 mmol), 3a (1.5 mmol), catalyst (0.1 mmol) in 3 cm3 solvent at 85 °C for 8 h
a
Catalyst (60 mg) at 8 °C for 12 h
The yield of 5 at 45 °C for 20 h. 13 % of 4a was also obtained
b
123

Heteropolyacid catalyzed formation of thioparabanic acid derivatives
Fig. 1 SEM of silica (left) SEM of supported H3PW12O40 on silica (middle and right)
effective in this transformation (not shown in Table 1).
Finally, HPA was selected as the acid of choice based on
the recycling and efficiency. A solvent screen showed that
i-PrOH gave best result (Table 1, entry 2). Reaction in
apolar solvent like toluene occurred to low conversions
(Table 1, entry 12). It is noteworthy that a moderate yield
of 4a was obtained in deionized water (Table 1, entry 14).
A variety of thiocyanate precursors were also examined in
order to evaluate the influence of the nature of the counter-
ion on reaction progress (Table 1, entries 15–18). Among
the thiocyanates examined, ammonium and lithium thio-
cyanates afforded the desired product in higher yield.
Finally, NH4SCN was selected as the reagent of choice
based on the cost and efficiency. Note that reaction con-
ducted at lower temperature (45 °C) in MeCN, formed 5 as
the main product (Table 1, entry 19). It could be deduced
that reaction temperature and solvent control the regiose-
lectivity of SCN anion.
the aromatic ring offers an opportunity for subsequent
cross-coupling, facilitating expedient synthesis of highly
complex thioparabanic acids. Varying the oxalate ester
structures had little effect on the outcome of the reaction
(Table 2, entries 22–25). Oxalic acid gave a competitively
lower yield of the desired product than those of oxalic
esters (Table 2, entry 26). Besides the oxalate esters and
acid, oxalyl chloride (3g) was also examined and gave the
desired product in nearly quantitative amount in the
absence of the catalyst (Table 2, entry 27).
The recycling of the catalyst was then examined using
the model reaction (Table 2, entries 19–21). After the
completion of the reaction, the catalyst was recovered by
filtration, followed by washing with ethanol (5 cm3 9 3).
After drying (80 °C for 8 h in vacuo), the catalyst was
reused directly for the next reaction. The catalytic activity
remained almost unchanged after two catalytic cycles,
indicating that the catalyst is stable and can be regenerated
for repeated use. However, the yield decreased as the cat-
alyst was used for the third run.
After having defined the optimum reaction conditions,
we sought to explore the scope of the reaction (Table 2).
Alkyl amines gave higher yields than those of aryl amines
which were likely due to the lower nucleophilicity of the
aromatic amines (Table 2, entries 1–4 and 11). 2-Chloro-
and 4-chlorobenzyl amine (1g, 1h) underwent effective
reaction under the optimized catalytic conditions (Table 2,
entries 7 and 8). This reaction is sensitive to steric effects
as ortho-substituted benzyl amine and aniline afforded the
desired products in lower yields (Table 2, entries 6 and 17).
Products containing a methoxy group could be obtained in
excellent yields (Table 2, entries 9 and 16). The presence
of electron withdrawing groups on aromatic ring highly
affected the reaction progress as p-nitro benzyl amine (1m)
was not compatible with this reaction (Table 2, entries
12–14). Substrates containing bromide on aromatic ring
gave the desired products in acceptable yields (Table 2,
entries 10 and 18). Notably, the tolerance for bromide on
The structures of products were confirmed by spectro-
scopic analyses. For example, the 1H NMR spectrum of 4a
showed all the signals in appropriate regions including
characteristic NH and CH2N signals. The 13C NMR spec-
trum of 4a exhibited seven signals in agreement with the
proposed structure. The mass spectrum of 4a displayed the
molecular ion peak at m/z = 186.
A tentative mechanism for this transformation is pro-
posed in Scheme 1. It is conceivable that the initial event is
the formation of the substituted 2-oxoacetyl isothiocyanate
6 from the amine, ammonium thiocyanate, and oxalate
ester using H3PW12O40. Intermediate
6
undergoes
cyclization to produce 7, which undergoes tautomerization
to yield 4.
In conclusion, we have described an efficient procedure
for the synthesis of thioparabanic acids. To our knowledge,
123

A. Samzadeh-Kermani
Table 2 Synthesis of functionalized thioparabanic acids
O
R1
S
O
N
O
R2
H3PW12O40
R1 NH2
NH4SCN
R2
+
+
NH
i-PrOH, 85 °C
O
8-11
h
1
2a
3
4
Entry
Amine
R1
Malonate
R2
Yield/%
1
1a
1b
1c
1d
1e
1f
n-Bu
t-Bu
Ph
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
EtO
EtO
EtO
EtO
EtO
EtO
EtO
EtO
EtO
EtO
EtO
4a, 93
4b, 92
4c, 85
4d, 94
4e, 93
4f, 87
4g, 89
4h, 87
4i, 98
4j, 87
4k, 94
2
3
4
Bn
5
4-CH3-Bn
2-CH3-Bn
2-Cl-Bn
6
7
1g
1h
1i
8
4-Cl-Bn
9
4-OMe-Bn
4-Br-Bn
10
11
1j
1k
Naphthyl-
CH2
12
1l
4-i-PrOCO-
Bn
3a
EtO
4l, 69
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
1m
1n
1o
1p
1q
1r
1a
1a
1a
1a
1a
1a
1a
1a
1a
4-NO2- Bn
3-CF3-C6H4
3-Me-C6H4
4-OMe-C6H4
2-Me-C6H4
4-Br-C6H4
n-Bu
3a
3a
3a
3a
3a
3a
3a
3a
3a
3b
3c
3d
3e
3f
EtO
EtO
EtO
EtO
EtO
EtO
EtO
EtO
EtO
MeO
BnO
i-PrO
t-BuO
OH
–
4m, 29
4n, 89
4o, 89
4p, 69
4q, 76
4d, 89a
4d, 80
4d, 65
4d, 91
4d, 90
4d, 84
4d, 95
4d, 61
4d, 99b
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
3g
Cl
For all entries except stated otherwise: 1 (1.0 mmol), 2a (1.5 mmol), 3 (1.5 mmol), H3PW12O40 (0.1 mmol), in 3 cm3 i-PrOH at 85 °C for 8 h
a
Entries 19–21 indicate the yield of the product in recycling tests, second through fourth runs
b
The yield was obtained in the absence of the catalyst
this work was the first example of the utilizing HPA for the
preparation of thioparabanic acid using amines, thio-
cyanates, and dialkyl oxalates. Using this procedure, a
simple recrystalization from CH2Cl2/acetone would suffice
to isolate the pure titled product. The optimized reaction
conditions reported herein are compatible with the presence
of functional groups such as CO2, OMe, Cl, Br, and CF3.
Experimental
All reagents were purchased from the Merck chemical
companies and used without further purification. Products
were characterized by different spectroscopic methods
(FT-IR, GC-Mass, and NMR spectra), elemental analysis
(CHN), and melting points. The NMR spectra were
123

Heteropolyacid catalyzed formation of thioparabanic acid derivatives
PrOH was stirred at 85 °C for 30 min. A solution of amine
(1.0 mmol) in 1 cm3 i-PrOH was then added to initial
mixture in one portion. The resulting mixture was heated
for an additional 8–11 h. After completion of reaction, the
mixture was diluted with 5 cm3 EtOAc and subsequently
5 cm3 sat. NH4Cl solution was added. The mixture was
stirred for additional 30 min, and two layers were sepa-
rated. The aqueous layer was extracted with EtOAc
(7 cm3 9 3). The combined organic layers were dried over
MgSO4, filtered, and concentrated in vacuo. The residue
was washed with ether and then recrystallized from CH2-
Cl2/acetone to give the pure desired product.
Scheme 1
MSCN
2
O
O
O
NHR1
R2
N
H3PW12O40
R1 NH2 + SCNM +
R2
C
S
i-PrOH, 85 °C
O
6
1
3
O
O
R1
N
R1
N
O
O
N
NH
HS
S
4
7
1-Butyl-2-thioxoimidazolidine-4,5-dione
(4a, C7H10N2O2S)
The crude product was purified by recrystallization from
CH2Cl2/acetone affording 0.17 g (93 %) 4a. Pale yellow
ꢀ
powder; m.p.: 71–74 °C; IR (KBr): m = 3271, 1753, 1737,
1
recorded in acetone-d6. H NMR spectra were recorded on
a Bruker Avance DRX 500 MHz instrument. The chemical
shifts (d) are reported in ppm relative to the TMS as
internal standard. J values are given in Hz. IR (KBr)
spectra were recorded on a Perkin-Elmer 781 spectropho-
tometer. Melting points were taken in open capillary tubes
with a BUCHI 510 melting point apparatus. The elemental
analysis was performed using Heraeus CHN-O-Rapid
analyzer. TLC was performed on silica gel poly-gram SIL
G/UV 254 plates. Morphology and particle dispersion was
investigated by scanning electron microscopy (SEM) (Cam
scan MV2300). All known compounds (4b, 4d, 4e, 4g–4i,
and 4k) gave satisfactory spectroscopic data and were
consistent with that reported in the literature [25] (see ESI
for characterization data for all products).
1659, 1441, 1314, 1124 cm-1 1H NMR (500 MHz,
;
acetone-d6): d = 0.92 (3H, t, 3J = 7.3 Hz, CH3), 1.35
(2H, m, CH2), 1.66 (2H, m, CH2), 3.91 (2H, t, 3J = 7.4 Hz,
CH2), 10.23 (1H, br s, NH) ppm; 13C NMR (125.7 MHz,
acetone-d6): d = 13.5 (CH3), 19.9 (CH2), 29.6 (CH2), 41.5
(CH2), 155.6 (C=O), 156.3 (C=O), 171.6 (C=S) ppm; EI-
MS (70 eV): m/z (%) = 186 (M?, 8), 144 (37), 115 (100),
99 (28), 71 (67).
1-(tert-Butyl)-2-thioxoimidazolidine-4,5-dione (4b) [25]
The crude product was purified by recrystallization from
CH2Cl2/acetone affording 0.17 g (92 %) 4b. Pale yellow
powder; m.p.: 93–96 °C.
1-Phenyl-2-thioxoimidazolidine-4,5-dione
(4c, C9H6N2O2S)
The crude product was purified by recrystallization from
CH2Cl2/acetone affording 0.17 g (85 %) 4c. Yellow pow-
General procedure for the preparation of catalyst
and 4
ꢀ
der; m.p.: 135–137 °C; IR (KBr): m = 3273, 1754, 1735,
1652, 1427, 1318, 1124 cm-1 1H NMR (500 MHz,
;
The heteropolyacids were prepared by a hydrothermal
synthesis method [31]. As an example H4PMo12O40 was
prepared according to the following procedure: a mixture
of 0.98 g phosphoric acid and 14.4 g molybdenum trioxide
was suspended in 150 cm3 distilled H2O and the mixture
stirred for 6 h at 80 °C. After cooling to 25 °C and removal
of insoluble molybdates, the heteropolyacid solution was
evaporated and dried at 85 °C for 24 h to give orange
crystals. Silica-supported HPA was prepared by the stan-
dard literature procedure [32]. A mixture of silica
acetone-d6): d = 7.29 (2H, d, 3J = 6.8 Hz, 2 CH),
7.47–7.54 (3H, m, 3 CH), 9.52 (1H, br s, NH) ppm; 13C
NMR (125.7 MHz, acetone-d6): d = 129.2 (CH), 130.6 (2
CH), 133.6 (2 CH), 139.4 (C), 161.5 (C=O), 162.3 (C=O),
174.7 (C=S) ppm; EI-MS (70 eV): m/z (%) = 206 (M?,
7), 164 (32), 135 (43), 119 (24), 92 (47), 77 (100).
1-Benzyl-2-thioxoimidazolidine-4,5-dione (4d) [25]
The crude product was purified by recrystallization from
CH2Cl2/acetone affording 0.21 g (94 %) 4d. Pale yellow
powder; m.p.: 152–154 °C (Ref. [25] 151–153 °C).
(DavisilTM, 200–425 mesh, 150 A) and HPA in H2O-i-
˚
PrOH or MeCN was stirred at 25 °C for 24 h. The catalyst
was washed with deionized H2O and dried at 110 °C for
12 h. The supported catalyst was then calcinated at 200 °C
for 3 h.
1-(4-Methylbenzyl)-2-thioxoimidazolidine-4,5-dione
(4e) [25]
The crude product was purified by recrystallization from
CH2Cl2/acetone affording 0.22 g (93 %) 4e. Pale yellow
powder; m.p.: 167–169 °C.
A mixture of ammonium thiocyanate (1.5 mmol), HPA
(0.1 mmol), and oxalate source (1.5 mmol) in 2 cm3 i-
123

A. Samzadeh-Kermani
1-(2-Methylbenzyl)-2-thioxoimidazolidine-4,5-dione
(4f, C11H10N2O2S)
powder; m.p.: 108–118 °C; IR (KBr): mꢀ = 3278, 1758,
1742, 1731, 1647, 1446, 1327, 1126 cm-1
;
1H NMR
3
The crude product was purified by recrystallization from
CH2Cl2/acetone affording 0.20 g (87 %) 4f. Pale yellow
(500 MHz, acetone-d6): d = 1.22 (6H, d, J = 6.7 Hz, 2
CH3), 5.04 (2H, s, CH2), 5.36 (1H, m, CH), 7.57–7.69 (4H,
m, 4 CH), 9.36 (H, br s, NH) ppm; 13C NMR (125.7 MHz,
CDCl3): d = 22.7 (2 CH3), 47.7 (CH2), 69.2 (CH), 127.2 (2
CH), 129.6 (C), 132.3 (2 CH), 138.9 (C), 155.9 (C=O),
157.2 (C=O), 167.1 (C=O), 176.8 (C=S) ppm; EI-MS
(70 eV): m/z (%) = 306 (M?, 5), 263 (14), 221 (20), 192
(69), 176 (28), 150 (36), 135 (17), 91 (100).
ꢀ
powder; m.p.: 159–162 °C; IR (KBr): m = 3283, 1760,
1
1738, 1658, 1460, 1323, 1128 cm-1; H NMR (500 MHz,
acetone-d6): d = 2.21 (3H, s, CH3), 5.21 (2H, s, CH2), 7.10
3
(1H, d, J = 7.5 Hz, CH), 7.20–7.29 (2H, m, 2 CH), 7.36
(1H, d, 3J = 7.7 Hz, CH), 9.57 (1H, s, NH) ppm; 13C NMR
(125.7 MHz, acetone-d6): d = 22.7 (CH3), 46.4 (CH2),
126.3 (CH), 127.1 (CH), 129.6 (CH), 131.5 (CH), 136.2
(C), 139.6 (C), 156.3 (C=O), 157.1 (C=O), 173.6 (C=S)
ppm; EI-MS (70 eV): m/z (%) = 234 (M?, 6), 192 (14),
163 (68), 147 (24), 121 (36), 106 (100).
2-Thioxo-1-[3-(trifluoromethyl)phenyl]imidazolidine-4,5-
dione (4m, C10H5F3N2O2S)
The crude product was purified by recrystallization from
CH2Cl2/acetone affording 0.08 g (29 %) 4m. Yellow
ꢀ
1-(2-Chlorobenzyl)-2-thioxoimidazolidine-4,5-dione
(4g) [25]
powder; m.p.: 119–121 °C; IR (KBr): m = 3278, 1764,
1
1738, 1651, 1437, 1326, 1125 cm-1; H NMR (500 MHz,
The crude product was purified by recrystallization from
CH2Cl2/acetone affording 0.23 g (89 %) 4g. Pale yellow
powder; m.p.: 164–167 °C.
acetone-d6): d = 7.20 (1H, m, CH), 7.48 (1H, d,
3J = 6.8 Hz, CH), 7.68 (1H, t, 3J = 6.8 Hz, CH), 7.76
(1H, s, CH), 9.74 (1H, br s, NH) ppm; 13C NMR
(125.7 MHz,
acetone-d6):
d = 124.2
(CH,
q,
1-(4-Chlorobenzyl)-2-thioxoimidazolidine-4,5-dione
(4h) [25]
3J = 3.8 Hz), 126.5 (CH, q, 3J = 3.8 Hz), 129.8 (CH),
1
131.0 (CF3, q, J = 270.2 Hz), 133.5 (CH), 135.2 (C, q,
The crude product was purified by recrystallization from
CH2Cl2/acetone affording 0.22 g (87 %) 4h. Pale yellow
powder; m.p.: 170–172 °C.
2J = 32.2 Hz), 139.3 (C), 155.7 (C=O), 156.2 (C=O),
176.4 (C=S) ppm; EI-MS (70 eV): m/z (%) = 274 (M?, 3),
232 (15), 203 (67), 187 (18), 161 (100).
1-(4-Methoxybenzyl)-2-thioxoimidazolidine-4,5-dione
(4i) [25]
2-Thioxo-1-(m-tolyl)imidazolidine-4,5-dione
(4n, C10H8N2O2S)
The crude product was purified by recrystallization from
CH2Cl2/acetone affording 0.24 g (98 %) 4i. Pale yellow
powder; m.p.: 173–176 °C.
The crude product was purified by recrystallization from
CH2Cl2/acetone affording 0.20 g (89 %) 4n. Yellow pow-
ꢀ
der; m.p.: 130–132 °C; IR (KBr): m = 3281, 1769, 1735,
1-(4-Bromobenzyl)-2-thioxoimidazolidine-4,5-dione
(4j, C10H7BrN2O2S)
1662, 1438, 1336, 1125 cm-1 1H NMR (500 MHz,
;
acetone-d6): d = 2.34 (3H, s, CH3), 6.93–6.96 (2H, m, 2
CH), 7.24 (1H, d, 3J = 7.5 Hz, CH), 7.37 (1H, s, CH), 9.68
(1H, s, NH) ppm; 13C NMR (125.7 MHz, acetone-d6):
d = 22.7 (CH3), 123.5 (CH), 124.8 (CH), 129.0 (CH),
130.6 (CH), 134.1 (C), 137.3 (C), 157.1 (C=O), 157.4
(C=O), 176.8 (C=S) ppm; EI-MS (70 eV): m/z (%) = 220
(M?, 6), 178 (12), 149 (72), 106 (100), 91 (51).
The crude product was purified by recrystallization from
CH2Cl2/acetone affording 0.26 g (87 %) 4j. Pale yellow
ꢀ
powder; m.p.: 182–184 °C; IR (KBr): m = 3292, 1763, 1737,
1652, 1424, 1336, 1128 cm-1; 1H NMR (500 MHz, acetone-
d6): d = 4.92 (2H, s, CH2), 7.27 (2H, d, 3J = 8.1 Hz, 2 CH),
7.78 (2H, d, 3J = 8.1 Hz, 2 CH), 9.45 (1H, s, NH) ppm; 13
C
NMR (125.7 MHz, acetone-d6): d = 50.2 (CH2), 123.4 (C),
127.1 (2 CH), 129.4 (2 CH), 134.1 (C), 154.7 (C=O), 157.0
(C=O), 174.3 (C=S) ppm; EI-MS (70 eV): m/z (%) = 299
(M?, 3), 255 (127), 227 (69), 211 (18), 185 (57), 169 (100).
1-(4-Methoxyphenyl)-2-thioxoimidazolidine-4,5-dione
(4o, C10H8N2O3S)
The crude product was purified by recrystallization from
CH2Cl2/acetone affording 0.21 g (89 %) 4o. Yellow pow-
ꢀ
1-(Naphthalen-1-yl)-2-thioxoimidazolidine-4,5-dione
(4k) [25]
der; m.p.: 153–155 °C; IR (KBr): m = 3282, 1767, 1738,
1668, 1442, 1342, 1125 cm-1 1H NMR (500 MHz,
;
The crude product was purified by recrystallization from
CH2Cl2/acetone affording 0.24 g (94 %) 4k. Pale yellow
powder; m.p.: 182–185 °C.
acetone-d6): d = 3.86 (3H, s, OCH3), 7.09 (2H, d,
3J = 7.6 Hz, 2 CH), 7.25 (2H, d, 3J = 7.5 Hz, 2 CH),
9.72 (1H, br s, NH) ppm; 13C NMR (125.7 MHz, acetone-
d6): d = 56.8 (OCH3), 116.3 (2 CH), 129.7 (2 CH), 132.4
(C), 156.3 (C=O), 157.1 (C=O), 159.1 (C), 176.2 (C=S)
ppm; EI-MS (70 eV): m/z (%) = 236 (M?, 8), 194 (17),
165 (71), 149 (21), 123 (58), 106 (100).
Isopropyl 4-[(4,5-dioxo-2-thioxoimidazolidin-1-yl)methyl]
benzoate (4l, C14H14N2O4S)
The crude product was purified by recrystallization from
CH2Cl2/acetone affording 0.21 g (69 %) 4l. Pale yellow
123

Heteropolyacid catalyzed formation of thioparabanic acid derivatives
Fujisawa T, Yokomizo A, Noguchi T (2009) Preparation of
imidazolecarboxamide derivatives as antibacterial agents. Chem
Abstr 151:148320 (WO 2009084614, Jul 9, 2009)
4. Murugana R, Anbazhaganb S, Narayanan S (2009) Eur J Med
Chem 44:3272
2-Thioxo-1-(o-tolyl)imidazolidine-4,5-dione
(4p, C10H8N2O2S)
The crude product was purified by recrystallization from
CH2Cl2/acetone affording 0.21 g (69 %) 4p. Yellow pow-
5. Tu SJ, Zhang XH, Han ZG, Cao XD, Wu SS, Yan S, Hao WJ,
Zhang G, Ma N (2009) J Comb Chem 11:428
6. Evdokimov NM, Kireev AS, Yakovenko AA, Antipin MY,
Magedov IV, Kornienko A (2007) J Org Chem 72:3443
7. Allais C, Grassot JM, Rodriguez J, Constantieux T (2014) Chem
Rev 114:10829
8. Yavari I, Ghazanfarpour-Darjani M, Sabbaghan M, Hossaini Z
(2007) Tetrahedron Lett 48:3749
9. Ghazanfarpour-Darjani M, Babapour-Kooshalshahi M, Mousavi-
Safavi SM, Akbari J, Khalaj M (2015) Synlett 27:259
10. Ma D, Lu X, Shi L, Zhang H, Jiang Y, Liu X (2011) Angew
Chem Int Ed 50:1118
ꢀ
der; m.p.: 121–124 °C; IR (KBr): m = 3282, 1758, 1730,
1651, 1449, 1342, 1125 cm-1 1H NMR (500 MHz,
;
acetone-d6): d = 2.20 (3H, s, CH3), 7.21–7.35 (3H, m, 3
CH), 7.53 (1H, t, 3J = 7.9 Hz, CH), 9.75 (1H, s, NH) ppm;
13C NMR (125.7 MHz, acetone-d6): d = 21.4 (CH3), 124.8
(CH), 129.4 (CH), 129.6 (CH), 131.1 (CH), 133.9 (C),
136.2 (C), 155.9 (C=O), 156.3 (C=O), 177.2 (C=S) ppm;
EI-MS (70 eV): m/z (%) = 220 (M?, 2), 176 (17), 149
(67), 133 (26), 106 (100), 91 (78).
1-(4-Bromophenyl)-2-thioxoimidazolidine-4,5-dione
(4q, C10H8N2O2S)
11. Yavari I, Ghazanfarpour-Darjani M, Nematpour
Tetrahedron Lett 56:2416
12. Yavari I, Ghazanfarpour-Darjani M, Bayat MJ, Malekafzali A
(2014) Synlett 25:959
13. Heravi MM, Sadjadi S (2009) J Iran Chem Soc 6:1
14. Kozhevnikov IV (1998) Chem Rev 98:171
15. Gulliya KS, Franck B, Schneider U, Sharma R, Arnold L, Mat-
thews JL (1994) Photooxidation products and derivatives thereof
of merocyanine-540, their preparation and uses as anticancer and
antiviral agents. Chem Abstr 121:108825 (US Patent 5,312,919,
May 17, 1994)
M (2015)
The crude product was purified by recrystallization from
CH2Cl2/acetone affording 0.22 g (76 %) 4q. Yellow pow-
ꢀ
der; m.p.: 167–169 °C; IR (KBr): m = 3284, 1767, 1738,
1652, 1436, 1334, 1126 cm-1
;
1H NMR (500 MHz,
3
acetone-d6): d = 7.47 (2H, d, J = 8.2 Hz, 2 CH), 7.74
(2H, d, J = 8.2 Hz, 2 CH), 9.85 (H, br s, NH) ppm; 13C
3
NMR (125.7 MHz, acetone-d6): d = 124.7 (C), 127.2 (2
CH), 131.8 (2 CH), 136.1 (C), 156.1 (C=O), 158.2 (C=O),
177.2 (C=S) ppm; EI-MS (70 eV): m/z (%) = 285 (M?, 5),
241 (12), 213 (69), 197 (17), 170 (100), 155 (47).
16. Gulliya KS, Sharam R, Liu HW, Arnold L, Matthews JL (1995)
Anticancer Drugs 6:545
17. Kotani T, Nagaki Y, Ishii A, Konishi Y, Yago H, Suehiro S,
Okukado N, Okamoto K (1997) J Med Chem 40:684
18. Butera JA, Elokdah HM, Sulkowski TS, Primeau JL, Lennox JR,
Graceffa RF (2006) Preparation of 1,3-disubstituted-2-thioxoim-
idazolidine-4,5-diones as potassium channel openers. Chem
Abstr 139:69265 (US Patent 7,115,620, October 3, 2006;
(2003))
19. Sunduru N, Srivastava K, Rajakumar S, Puri SK, Saxena JK,
Chauhan PM (2009) Bioorg Med Chem Lett 19:2570
20. Elokdah H, Sulkowski TS, Gharbia MA, Butera JA, Chai SY,
Mcfarlane GR, Mckean ML, Babiak JL, Adelman SJ, Quine EM
(2004) J Med Chem 47:681
21. Fahmy HH, Soliman GA (2001) Arch Pharm Res 24:180
22. Elokdah H, Sulkowski TS (2003) Preparation of 1,3-disubsti-
tuted-2-thioxoimidazolidine-4,5-diones for the treatment of
atherosclerosis. Chem Abstr 139:69264 (US Patent
20030119889, Jun 26, 2003)
3-Butylthiazolidine-2,4,5-trione (5, C7H9NO3)
The crude product was purified by recrystallization from
CH2Cl2/acetone affording 0.11 g (61 %) 5. Yellow oily
ꢀ
solid; IR (KBr): m = 3205, 1762, 1748, 1736, 1445, 1312,
1136 cm-1 1H NMR (500 MHz, acetone-d6): d = 0.87
;
(3H, t, 3J = 7.8 Hz, CH3), 1.28 (2H, m, CH2), 1.61 (2H, m,
CH2), 3.73 (2H, t, 3J = 7.2 Hz, CH2) ppm; 13C NMR
(125.7 MHz, acetone-d6): d = 14.8 (CH3), 21.3 (CH2),
30.8 (CH2), 47.5 (CH2), 159.8 (C=O), 174.1 (C=O), 192.9
(C=O) ppm; EI-MS (70 eV): m/z (%) = 187 (M?, 3), 159
(25), 133 (46), 99 (73), 73 (100).
23. Schmeyers J, Kaupp G (2002) Tetrahedron 58:7241
24. Aragoni MC, Arca M, Devillanova FA, Hursthouse MB, Huth
SL, Isaia F, Lippolis V, Mancini A, Ogilvie HR, Verani G (2005)
J Organomet Chem 690:1923
Acknowledgments Generous financial support from the Zabol
University of Iran is gratefully acknowledged.
25. Yavari I, Souri S, Sirouspour M (2008) Synlett 19:1633
26. Samzadeh-Kermani A (2014) Monatsh Chem 145:611
27. Samzadeh-Kermani A (2014) Synlett 25:1839
28. Samzadeh-Kermani A (2015) Synlett 26:643
29. Samzadeh-Kermani A (2016) Monatsh Chem 147:761
30. Bardin BB, Bordawekar SV, Neurock M, Davis RJ (1998) J Phys
Chem B 102:10819
References
1. Ward SE, Harrington FP, Gordon LJ, Hopley SC, Scott CM,
Watson JM (2005) J Med Chem 48:3478
2. Massari S, Daelemans D, Barreca ML, Knezevich A, Sabatini S,
Cecchetti V, Marcello A, Pannecouque C, Tabarrini O (2010) J
Med Chem 53:641
31. Tsigdinos GA, Hallada C (1968) J Inorg Chem 7:437
32. Izumi Y, Hasebe R, Urabe K (1983) J Catal 84:402
3. Soneda T, Takeshita H, Kagoshima Y, Yamamoto Y, Hosokawa
T, Konosu T, Masuda N, Uchida T, Achiwa I, Kuroyanagi J,
123