Chemoselective synthesis of functionalized 2,5-dihydro-2-thioxo-1H- imidazoles from 5,5-diarylthiohydantoins and activated acetylenes

Article abstract of DOI:10.1080/10426501003752179

Stable crystalline phosphorus ylides are obtained in excellent yields from the 1:1:1 addition reaction between 5,5-diarylthiohydantoins and dialkyl acetylenedicarboxylates in the presence of triphenylphosphine. These phosphoranes undergo a smooth intramol

Full text of DOI:10.1080/10426501003752179

This article was downloaded by: [Dicle University]
On: 08 November 2014, At: 12:50
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Phosphorus, Sulfur, and Silicon and the
Related Elements
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/gpss20
Chemoselective Synthesis of
Functionalized 2,5-Dihydro-2-
thioxo-1H-imidazoles from 5,5-
Diarylthiohydantoins and Activated
Acetylenes
Issa Yavari a , Mohammad M. Ghanbari a , Ashraf S. Shahvelayati a &
Maryam Ghazvini a
a Chemistry Department , Islamic Azad University , Science and
Research Branch, Ponak, Tehran, Iran
Published online: 19 Nov 2010.
To cite this article: Issa Yavari , Mohammad M. Ghanbari , Ashraf S. Shahvelayati & Maryam Ghazvini
(2010) Chemoselective Synthesis of Functionalized 2,5-Dihydro-2-thioxo-1H-imidazoles from 5,5-
Diarylthiohydantoins and Activated Acetylenes, Phosphorus, Sulfur, and Silicon and the Related
Elements, 185:12, 2551-2557, DOI: 10.1080/10426501003752179
To link to this article: http://dx.doi.org/10.1080/10426501003752179
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the
“Content”) contained in the publications on our platform. However, Taylor & Francis,
our agents, and our licensors make no representations or warranties whatsoever as to
the accuracy, completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content
should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims,
proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or
howsoever caused arising directly or indirectly in connection with, in relation to or arising
out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden. Terms &

Conditions of access and use can be found at http://www.tandfonline.com/page/terms-
and-conditions

Phosphorus, Sulfur, and Silicon, 185:2551–2557, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426501003752179
CHEMOSELECTIVE SYNTHESIS OF FUNCTIONALIZED
2,5-DIHYDRO-2-THIOXO-1H-IMIDAZOLES FROM
5,5-DIARYLTHIOHYDANTOINS AND ACTIVATED
ACETYLENES
Issa Yavari, Mohammad M. Ghanbari, Ashraf S. Shahvelayati,
and Maryam Ghazvini
Chemistry Department, Islamic Azad University, Science and Research Branch,
Ponak, Tehran, Iran
Stable crystalline phosphorus ylides are obtained in excellent yields from the 1:1:1 addition
reaction between 5,5-diarylthiohydantoins and dialkyl acetylenedicarboxylates in the pres-
ence of triphenylphosphine. These phosphoranes undergo a smooth intramolecular Wittig
reaction followed by an electrocyclic ring opening to produce dialkyl 2-(2,5-dihydro-5,5-
diaryl-2-thioxo-1H-imidazol-4-yl)but-2-enedioates in good yields.
Keywords Acetylenic ester; 2,5-dihydro-2-thioxo-1H-imidazole; intramolecular Wittig reac-
tion; thiohydantoin; triphenylphosphine
INTRODUCTION
Thiohydantoins represent an important class of biologically active molecules of
broad medicinal and agrochemical applications. Furthermore, many thiohydantoins are
responsible for inhibition of fatty acid hydrolases, glycogen phosphorylases, amylases, and
serine proteases.1–3
As part of our study on the development of new routes to heterocyclic and carbocyclic
systems,4−10 we report in this article on the chemoselective synthesis of functionalized
2,5-dihydro-5,5-diaryl-2-thioxo-1H-imidazoles 4. Thus, the reaction of diarylthiohydan-
toins 1 (5,5-diaryl-2-thioxoimidazolidin-4-one) with activated acetylenes 2 in the presence
of triphenylphosphine (Ph3P) leads to the phosphoranes 3. These phosphoranes undergo
intramolecular Wittig reaction7–11 in boiling toluene to produce dialkyl 2-(2,5-dihydro-5,5-
diaryl-2-thioxo-1H-imidazol-4-yl)but-2-enedioates 4 in good yields (Scheme 1).
RESULTS AND DISCUSSION
The reaction of 5,5-diarylthiohydantoins 1 with dialkyl acetylenedicarboxylates 2
in the presence of Ph3P proceeded at room temperature in CH2Cl2, and was completed
Received 4 January 2010; accepted 5 March 2010.
Address correspondence to Issa Yavari, Chemistry Department, Islamic Azad University, Science and
Research Branch, Ponak, P.O. Box 14155-4933, Tehran 1477893855, Iran. E-mail: yavarisa@modares.ac.ir
2551

2552
I. YAVARI ET AL.
S
S
S
PPh3
CO2R
CO2R
HN
CO2R
HN
HN
Ar
Ar
Ar
Ar
Ar
CH2Cl2
r.t.
Toluene
Reflux
N
PPh3
+
+
NH
N
Ar
CO2R
CHCO2R
O
RO2C
R
O
R
Ar
R
Me
Et
Ar
Ph
p-Tolyl
Ar
1a
1b
2a
2b
Me Ph
Me p-Tolyl
Me Ph
Me p-Tolyl
3a
3b
4a
4b
3c Et Ph
4c Et Ph
Et p-Tolyl
4d
Et p-Tolyl
3d
Scheme 1 Synthesis of compounds 3 and 4.
within a few hours. 1H and 13C NMR spectra of the crude products clearly in-
dicated the formation of dialkyl 2-(5,5-diphenyl-2-thioxoimidazolidin-4-one)-3-
(triphenylphosphanylidene)succinates 3 (Scheme 1). No products other than 3 could
be detected in the reaction mixture. The structure of compounds 3a–3d was deduced
1
from their IR, H, and 13C NMR spectra. The mass spectra of these stable phosphoranes
displayed molecular ion peaks at appropriate m/z values. Any initial fragmentation involved
loss from, or complete loss of, the side chains and scission of the heterocyclic ring system.
Phosphorus ylides 3 undergo a smooth intramolecular Wittig reaction followed by an
electrocyclic ring opening reaction in boiling toluene to produce dialkyl 2-(2,5-dihydro-5,5-
diaryl-2-thioxo-1H-imidazol-4-yl)but-2-enedioates 4 (Scheme 1). Structure 4 was assigned
to the isolated products on the basis of their elemental analyses and IR, 1H, and 13C NMR
and mass spectral data. Thus, the 1H NMR spectra of 4a–4d exhibited the C CH signals at
7.1–7.2 ppm, which is in agreement with the (E) configuration12 for the vinyl moiety of 4.
Further evidence was obtained from the 13C NMR spectra, which displayed C CH carbon
resonances at about 129–131 ppm and a C S carbon signal at about 183 ppm.
Although we have not yet established experimental proof for the mechanism of
the formation of compounds 3 and 4, a plausible mechanism was proposed as shown in
Scheme 2. It is reasonable to assume that phosphorus ylide 3 results from the initial addition
of Ph3P to the acetylenic ester and subsequent protonation of the 1:1 adduct 5, followed by
S
CO2R
CHCO2R
CO2R
+ 2
HN
Ar
Ar
+
PPh3
1
CO2R
+
N
Ph3P
Ph3P
O
5
6
7
S
S
PPh3
CO2R
CO2R
HN
Ar
Ar
HN
Intramolecular
Wittig reaction
Ar
Ar
Electrocyclic
ring opening
N
4
N
CO2R
O
RO2C
8
3
Scheme 2 A plausible mechanism for the formation of compounds 3 and 4.

FUNCTIONALIZED 2,5-DIHYDRO-2-THIOXO-1H-IMIDAZOLES
2553
attack of the anionic nitrogen of 7, formed by deprotonation of the acidic N-H hydrogen
of compound 2, at the vinylphosphonium cation 6 to form the phosphoranes 3. Ylides 3
undergo a chemoselective intramolecular Witting reaction7–11 to produce the fused bicyclic
intermediates 8, which apparently undergo an electrocyclic ring opening reaction under the
reaction conditions employed to produce the final products 4.
The 1H and 13C NMR spectra of the ylides 3a–3d are consisted with the presence of
two diastereoisomers. The ylide moiety of these compounds is strongly conjugated with the
adjacent carbonyl group, and rotation about the partial double bond in the (E)-3 and (Z)-3
geometrical isomers (Scheme 3) is slow on the NMR time scale at ambient temperature.
The free-energy of activation for interconversion of the geometrical isomers in similar
phosphoranes has been determined by dynamic NMR spectroscopy to be about 65–70 kJ
mol−1 4–6
.
Scheme 3 (E)- and (Z)-stereoisomers of compound 3.
The 1H and 13C NMR spectra of compounds 4 showed two different aryl groups, and
1
the H NMR spectra of compounds 4b and 4d exhibited characteristic (AB)X3 patterns
for the diastereotopic methylene protons. The Ar-CH3 region of the 1H NMR spectrum of
4d in CDCl3 at ambient temperature displayed two sharp singlets for the Ar-CH3 groups.
The 1H NMR of 4d in 1,2-dichlorobenzene at 25◦C is similar to that measured in CDCl3.
Increasing the temperature results in coalescence of the Ar-CH3 resonances. At 90◦C, a
relatively broad singlet was observed for the Ar-CH3 groups. This dynamic NMR effect is
attributed to restricted rotation around the single bond attaching the vinyl substituent to the
2-thioxo-1H-imidazole ring system.
Although an extensive line shape analysis in relation to the dynamic NMR effect
observed for 4d was not undertaken in the present work, the variable temperature spectra
are sufficient to calculate the free-energy barrier for the restricted rotation around C C
bond. From the coalescence of the Ar-CH3 protons and by using the expression k =
πꢀν/1.42, the first-order rate constant (k) was calculated. Application of the absolute rate
theory with a transmission coefficient of 1 gives a free-energy of activation (ꢀG=) of 71
2 kJ mol−1 for 4d, where all known sources of error are estimated and included.12
In summary, we have prepared novel thioxohydantoin-containing phosphorus ylides
via one-pot reaction between Ph3P and dialkyl acetylenedicarboxylates in the presence of
strong NH-acidic 5,5-diarylthioxohydantoins. These phosphorans are converted to func-
tionalized 2,5-dihydro-2-thioxo-1H-imidazoles. The procedure described here provides an
acceptable method for the preparation of phosphoranes bearing a thioxohydantoin moiety,
which can be employed for the synthesis of 2-thioxo-1H-imidazoles.

2554
I. YAVARI ET AL.
EXPERIMENTAL
Acetylenic esters 1 and Ph3P were obtained from Fluka and were used without further
purification. 5,5-Diarylthiohydantoins 2 were prepared by known methods.13 Melting points
were measured on an Electrothermal 9100 apparatus. Elemental analyses for C, H, N, and
S were performed using a Heraeus CHN-O-Rapid analyzer. The experimental data were in
1
good agreement with the calculated values. The H and 13C NMR spectra (CDCl3) were
measured with a Bruker DRX-300 Avance spectrometer. IR spectra were recorded on a
Shimadzu IR-460 spectrometer. Chromatography columns were prepared from Aldrich
silica gel 70–230 mesh.
General Procedure for the Preparation of Phosphorus Ylides 3
To a stirred solution of 2 mmol of 1 and 2 mmol of 2 in CH2Cl2 (5 mL), a solution of
0.52 g of Ph3P (2 mmol) in CH2Cl2 (2 mL) was added dropwise at 5◦C over 10 min. After
3 h stirring at r.t., the product was filtered and washed with cold AcOEt.
Dimethyl 2-(5,5-diphenyl-2-thioxoimidazolidin-4-one)-3-(triphenylphos-
phanylidene)succinate (3a). Yellow powder; mp: 184–186◦C; yield: 0.97 g (72%).
IR (KBr) (νmax/cm−1): 3440 (NH), 1743 (C O), 1437 (C C). Anal. Calcd (%) for
C39H33N2O5PS (672.73): C, 69.63; H, 4.94; N, 4.16; S, 4.77. Found: C, 70.10; H, 5.06; N,
4.25; S, 4.61. EI-MS: m/z (%): 672 (M+, 4), 595 (16), 266 (17), 224 (100), 166 (78), 77
(43), 59 (11), 31 (59).
Major isomer (Z)-3a (55%): 1H NMR (300 MHz, CDCl3): δ = 3.12 (3 H, s, MeO),
3.83 (3 H, s, MeO), 5.31 (1 H, d, 3JPC = 15.5, CH), 7.33–7.72 (25 H, m, 5 C6H5), 8.34 (1
1
H, s, NH). 13C NMR (75 MHz, CDCl3): δ = 37.1 (d, JPC = 130.2, P C), 49.3 (MeO),
2
1
50.4 (MeO), 57.0 (d, JPC = 17.1, CH), 71.0 (C), 127.3 (d, JPC = 91.3, P–Cipso), 127.4
(CH), 128.2 (CH), 128.9 (d, 3JPC = 12.2, Cmeta), 129.4 (CH), 132.1 (d, 4JPC = 2.0, Cpara),
2
2
134.0 (d, JPC = 11.1, Cortho), 139.1 (Cipso), 165.6 (COO), 170.1 (d, Jpc = 14.0, COO),
172.2 (C O), 182.1 (C S).
Minor isomer (E)-3a (45%): 1H NMR (300 MHz, CDCl3): δ = 3.52 (3 H, s, MeO),
3.79 (3 H, s, MeO), 5.31 (1 H, d, 3Jpc = 17.5, CH), 7.33–7.72 (25 H, m, 5 C6H5), 8.34 (1
H, s, NH); 13C NMR (75 MHz, CDCl3): δ = 38.5 (d, 1JPC = 140.0, P–C), 49.4 (MeO), 53.2
(MeO), 56.5 (d, 2JPC = 17.2, CH), 71.0 (C), 126.5 (d, 1JPC = 93.3, P–Cipso), 127.4 (CH),
128.3 (CH), 129.2 (d, 3JPC = 12.2, Cmeta), 129.4 (CH), 132.3 (d, 4JPC = 1.9, Cpara), 134.1
2
(d, 2JPC = 11.2, Cortho), 139.2 (Cipso), 165.7 (COO), 170.1 (d, JPC = 14.1, COO), 172.3
(C O), 182.2 (C S).
Dimethyl 2-(5,5-di-p-tolyl-2-thioxoimidazolidin-4-one)-3-(triphenylphos-
phanylidene)succinate (3b). Yellow powder; mp: 180–183◦C; yield: 0.86 g (62%).
IR (KBr) (νmax/cm−1): 3478 (NH), 1747 (C O), 1493 (C C). Anal. Calcd (%) for
C41H37N2O5PS (700.78): C, 70.27; H, 5.32; N, 4.00; S, 4.58. Found: C, 70.01; H, 5.26;
N, 3.90; S, 4.41. EI-MS: m/z (%):700 (M+, 2), 623 (12), 294 (18), 252 (100), 194 (69), 91
(35), 77 (23), 59 (8), 31 (65).
1
Major isomer (Z)-3b (54%): H NMR (300 MHz, CDCl3): δ = 2.34 (3 H, s, Me),
3
2.35 (3 H, s, Me), 3.10 (3 H, s, MeO), 3.83 (3 H, s, MeO), 5.28 (1 H, d, JPC = 15.5,
CH), 7.05–7.98 (23 H, m, 3 C6H5, 2 C6H4), 8.62 (1 H, s, NH). 13C NMR (75 MHz,
CDCl3): δ = 21.5 (Me), 21.6 (Me), 37.1 (d, 1JPC = 130, P C), 49.4 (MeO), 52.7 (MeO),
2
1
57.0 (d, JPC = 17.0, CH), 71.5 (C), 127.1 (CH), 127.3 (d, JPC = 91, P–Cipso), 128.3
3
4
(CH), 128.9 (d, JPC = 12.1, Cmeta), 129.4 (CH), 132.1 (d, JPC = 2.0, Cpara), 134.0

FUNCTIONALIZED 2,5-DIHYDRO-2-THIOXO-1H-IMIDAZOLES
2555
2
2
(d, JPC = 11.1, Cortho), 139.0 (Cipso), 165.7 (COO), 170.1 (d, Jpc = 14.2, COO), 172.1
(C O), 183.2 (C S).
1
Minor isomer (E)-3b (46%): H NMR (300 MHz, CDCl3): δ = 2.34 (3 H, s, Me),
2.35 (3 H, s, Me), 3.53 (3 H, s, MeO), 3.78 (3 H, s, MeO), 5.28 (1 H, d, 3JPC = 17.5, CH),
7.35–7.98 (23 H, m, 3 C6H5, 2 C6H4), 8.62 (1 H, s, NH). 13C NMR (75 MHz, CDCl3):
δ = 21.5 (Me), 21.6 (Me), 38.5 (d, 1JPC = 140.1, P C), 49.4 (MeO), 53.3 (MeO), 56.5 (d,
2JPC = 17.0, CH), 71.5 (C), 126.5 (d, 1JPC = 93.2, P–Cipso), 127.1 (CH), 128.3 (CH), 129.2
3
4
2
(d, JPC = 12.0, Cmeta), 129.4 (CH), 132.3 (d, JPC = 1.9, Cpara), 134.1 (d, JPC = 11.2,
2
Cortho), 139.1 (Cipso), 165.8 (COO), 170.1 (d, JPC = 14.0, COO), 172.2 (C O), 183.3
(C S).
Diethyl 2-(5,5-diphenyl-2-thioxoimidazolidin-4-one)-3-(triphenylphos-
phanylidene)succinate (3c). Yellow powder; mp: 170–172◦C; yield: 0.89 g (64%).
IR (KBr) (νmax/cm−1): 3468 (NH), 1729 (C O), 1489 (C C). Anal. Calcd (%) for
C41H37N2O5PS (700.78): C, 70.27; H, 5.32; N, 4.00; S, 4.58. Found: C, 70.05; H, 5.26; N,
3.89; S, 4.50. EI-MS: m/z (%):700 (M+, 3), 623 (16), 266 (20), 225 (100), 166 (82), 77
(39), 73 (15), 45 (71).
Major isomer (Z)-3c (60%): 1H NMR (500 MHz, CDCl3): δ = 0.38 (3 H, t, 3JHH
=
7.2, Me), 1.27 (3 H, t, 3JHH = 7.0, Me), 3.64–3.82 (2 H, complex (AB)X3 system, CH2O),
4.00 (2 H, q, 3JHH = 7.2, CH2O), 5.31 (1 H, d, 3JPC = 15.5, CH), 7.33–7.72 (25 H, m, 5
C6H5), 8.34 (1 H, s, NH). 13C NMR (125 MHz, CDCl3): δ = 13.9 (Me), 14.2 (Me), 36.7
(d, 1JPC = 130.0, P C), 57.6 (CH2O), 60.0 (d, 2JPC = 18.0, CH), 60.3 (CH2O), 71.3 (C),
1
3
127.1 (d, JPC = 89.2, P–Cipso), 127.0 (CH), 127.9 (CH), 128.4 (d, JPC = 12.1, Cmeta),
131.7 (CH), 131.8 (d, 4JPC = 1.9, Cpara), 132.2 (d, 2JPC = 10.3, Cortho), 139.0 (Cipso), 168.4
(COO), 170.1 (d, 2Jpc = 14.0, COO), 171.3 (C O), 183.2 (C S).
Minor isomer (E)-3c (40%): 1H NMR (500 MHz, CDCl3): δ = 1.11 (3 H, t, 3JHH
=
7.2, Me), 1.34 (3 H, t, 3JHH = 7.2, Me), 4.07–4.21 (2 H, complex (AB)X3 system, CH2O),
4.28 (2 H, q, 3JHH = 7.2, CH2O), 5.31 (1 H, d, 3JPC = 17.5, CH), 7.33–7.72 (25 H, m, 5
C6H5), 8.34 (1 H, s, NH). 13C NMR (125 MHz, CDCl3): δ = 14.1 (Me), 14.7 (Me), 38.5 (d,
1JPC = 140, P C), 58.7 (CH2O), 59.3 (d, 2JPC = 18.0, CH), 60.4 (CH2O), 71.3 (C), 126.5
(d, 1JPC = 91, P–Cipso), 127.1 (CH), 128.1 (CH), 128.7 (d, 3JPC = 12.2, Cmeta), 131.8 (CH),
4
2
131.9 (d, JPC = 1.8, Cpara), 133.7 (d, JPC = 10.1, Cortho), 139.1 (Cipso), 168.5 (COO),
170.1 (d, 2JPC = 14.1, COO), 172.3 (C O), 183.3 (C S).
Diethyl 2-(5,5-di-p-tolyl-2-thioxoimidazolidin-4-one)-3-(triphenylphos-
phanylidene)succinate (3d). Yellow powder; mp: 174–176◦C; yield: 0.80 g (55%).
IR (KBr) (νmax/cm−1): 3420 (NH), 1665 (C O), 1430 (C C). Anal. Calcd (%) for
C43H41N2O5PS (728.83): C, 70.86; H, 5.67; N, 3.84; S, 4.40. Found: C, 69.98; H, 5.56; N,
3.96; S, 4.62. EI-MS: m/z (%):728 (M+, 2), 651 (15), 294 (24), 252 (100), 194 (75), 91
(41), 77 (22), 73 (9), 45 (62).
Major isomer (Z)-3d (57%): 1H NMR (300 MHz, CDCl3): δ = 0.38 (3 H, t, 3JHH
=
3
7.2, Me), 1.27 (3 H, t, JHH = 7.2, Me), 2.34 (3 H, s Me), 2.35 (3 H, s, Me), 3.64–3.82
3
(2 H, complex (AB)X3 system, CH2O), 4.00 (2 H, q, JHH = 7.2, CH2O), 5.30 (1 H, d,
3JPC = 15.5, CH), 7.33–7.72 (23 H, m, 3 C6H5, 2 C6H4), 8.34 (1 H, s, NH). 13C NMR (75
1
MHz, CDCl3): δ = 13.9 (Me), 14.2 (Me), 21.5 (Me), 21.6 (Me), 36.7 (d, JPC = 131.2,
P C), 58.8 (CH2O), 61.8 (CH2O), 57.0 (d, 2JPC = 17.0, CH), 71.3 (C), 127.1 (d, 1JPC
=
89.3, P–Cipso), 127.0 (CH), 127.9 (CH), 128.4 (d, 3JPC = 12.2, Cmeta), 131.7 (CH), 131.9
4
2
(d, JPC = 1.8, Cpara), 132.3 (d, JPC = 10.7, Cortho), 139.1 (Cipso), 165.4 (C O), 171.9
(COO), 170.1 (d, 2JPC = 14.1, COO), 183.2 (C S).

2556
I. YAVARI ET AL.
Minor isomer (E)-3d (43%): 1H NMR (300 MHz, CDCl3): δ = 1.11 (3 H, t, 3JHH
=
3
7.0, Me), 1.34 (3 H, t, JHH = 7.0, Me), 2.34 (3 H, s, Me), 2.35 (3 H, s, Me), 4.07–4.21
3
(2 H, complex (AB)X3 system, CH2O), 4.28 (2 H, q, JHH = 7.2, CH2O), 5.31 (1 H, d,
3JPC = 17.5, CH), 7.33–7.72 (23 H, m, 3 C6H5, 2 C6H4), 8.34 (1 H, s, NH). 13C NMR (75
1
MHz, CDCl3): δ = 14.1 (Me), 14.7 (Me), 21.5 (Me), 21.6 (Me), 38.5 (d, JPC = 140.2,
P C), 58.7 (CH2O), 61.7 (CH2O), 56.7 (d, 2JPC = 17.1, CH), 71.3 (C), 126.5 (d, 1JPC
=
91.2, P–Cipso), 127.2 (CH), 128.1 (CH), 128.7 (d, 3JPC = 12.2, Cmeta), 131.8 (CH), 131.9
(d, 4JPC = 2.0, Cpara), 133.7 (d, 2JPC = 10.4, Cortho), 139.2 (Cipso), 165.8 (COO), 170.1 (d,
2JPC = 14.1, COO), 172.3 (C O), 183.3 (C S).
General Procedure for Conversion of 3 to 4
A solution of 1.2 mmol of 3 in toluene (20 mL) was refluxed for 12 h. The solvent
was removed under reduced pressure, and the yellowish oil was extracted using cold Et2O.
Then, the ether layer was evaporated under reduced pressure, and the residue was separated
by silica column chromatography (Merck 230–400 mesh) using hexane/AcOEt as eluent
to afford pure imidazoles 4.
Dimethyl 2-(2,5-dihydro-5,5-diphenyl-2-thioxo-1H-imidazol-4-yl)but-2-
enedioate (4a). Colorless crystals; mp: 155–157◦C; yield: 0.38 g (81%). IR (KBr)
(νmax/cm−1): 3478 (NH), 1765 and 1720 (C O). Anal. Calcd (%) for C21H18N2O4S
(394.44): C, 63.94; H, 4.60; N, 7.10; S, 8.13. Found: C, 63.90; H, 4.46; N, 6.91; S, 8.21.
EIMS: m/z (%): 394 (M+, 15), 316 (25), 225 (30), 166 (100), 77 (28), 59 (12), 31 (21). 1H
NMR (300 MHz, CDCl3): δ = 3.50 (3 H, s, MeO), 3.85 (3 H, s, MeO), 7.20 (1 H, s, CH),
7.41–7.50 (10 H, m, 10 CH), 8.02 (1 H, s, NH). 13C NMR (75 MHz, CDCl3): δ = 52.7
(MeO), 53.9 (MeO), 74.3 (C), 127.7 (2 CH), 127.8 (2 CH), 129.3 (2 CH), 129.5 (2 CH),
129.6 (CH), 131.0 (CH), 132.4 (CH), 131.2 (C), 137.3 (C), 138.4 (C), 162.2 (COO), 162.9
(COO), 171.8 (C N), 180.3 (C S).
Dimethyl 2-(2,5-dihydro-2-thioxo-5,5-di-p-tolyl-1H-imidazol-4-yl)but-2-
enedioate (4b). Colorless crystals; mp: 162–164◦C; yield: 0.43 g (85%). IR (KBr)
(νmax/cm−1): 3344 (NH), 1760 and 1714 (C O). Anal. Calcd (%) for C23H22N2O4S
(422.50): C, 65.38; H, 5.25; N, 6.63; S, 7.59. Found: C, 65.70; H, 5.16; N, 6.59; S, 7.51.
EI-MS: m/z (%): 422 (M+, 14), 330 (21), 252 (44), 194 (100), 91 (76), 59 (18), 31 (24). 1H
NMR (300 MHz, CDCl3): δ = 2.37 (3 H, s, Me), 2.39 (3 H, s, Me), 3.53 (3 H, s, MeO),
3.85 (3 H, s, MeO), 7.21 (1 H, s, CH), 7.34–7.72 (8 H, m, CH), 7.83 (1 H, s, NH). 13C
NMR (75 MHz, CDCl3): δ = 21.5 (Me), 23.0 (Me), 52.7 (MeO), 53.9 (MeO), 74.0 (C),
127.7 (2 CH), 127.8 (2 CH), 129.3 (2 CH), 129.5 (2 CH), 129.6 (CH), 131.0 (CH), 131.2
(C), 132.5 (CH), 137.3 (C), 138.4 (C), 162.3 (COO), 162.9 (COO), 171.8 (C N), 180.3
(C S).
Diethyl
2-(2,5-dihydro-5,5-diphenyl-2-thioxo-1H-imidazol-4-yl)but-2-
enedioate (4c). Colorless crystals; mp: 151–153◦C; yield: 0.38 g (75%). IR (KBr)
(νmax/cm−1): 3468 (NH), 1765 and 1703 (C O). Anal. Calcd (%) for C23H22N2O4S
(422.50): C, 65.38; H, 5.25; N, 6.63; S, 7.59. Found: C, 65.78; H, 5.18; N, 6.56; S, 7.54.
EI-MS: m/z (%): 422 (M+, 17), 344 (28), 225 (36), 166 (100), 77 (25), 73 (13), 45 (23).1H
3
3
NMR (300 MHz, CDCl3): δ = 0.91 (3 H, t, JHH = 7.2, Me), 1.13 (3 H, t, JHH = 7.2,
3
3
2
Me), 3.97–4.13 (2 H, m, (AB)X3 system, JAX = 7.2, JBX = 7.2, JAB = 12.1, CH2O),
3
4.28 (2 H, q, JHH = 7.2, CH2O), 7.16 (1 H, s, CH), 7.30–7.73 (10 H, m, 10 CH), 8.29
(1 H, s, NH). 13C NMR (75 MHz, CDCl3): δ = 14.2 (Me), 14.3 (Me), 62.0 (CH2O), 63.3

FUNCTIONALIZED 2,5-DIHYDRO-2-THIOXO-1H-IMIDAZOLES
2557
(CH2O), 74.2 (C), 127.7 (2 CH), 127.9 (2 CH), 129.3(2 CH), 129.4 (2 CH), 129.5 (CH),
131.3 (CH), 132.5 (CH), 131.4 (C), 137.4 (C), 138.5 (C), 161.8 (COO), 162.6 (COO),
171.8 (C N), 180.5 (C S).
Diethyl
2-(2,5-dihydro-2-thioxo-5,5-di-p-tolyl-1H-imidazol-4-yl)but-2-
enedioate (4d). Colorless crystals; mp: 156–158◦C; yield: 0.34 g (63%). IR (KBr)
(νmax/cm−1): 3338 (NH), 1762 and 1725 (C O). Anal. Calcd (%) for C25H26N2O4S
(450.55): C, 66.64; H, 5.82; N, 6.22; S, 7.12. Found: C, 66.90; H, 5.70; N, 6.11; S, 7.21.
EI-MS: m/z (%): 450 (M+, 12), 358 (26), 252 (51), 194 (100), 91 (63), 73 (21), 31 (30). 1H
NMR (300 MHz, CDCl3): δ = 0.91 (3H, t, 3JHH = 7.2, Me), 1.13 (3 H, t, 3JHH = 7.2, Me),
2.37 (3 H, s, Me), 2.40 (3 H, s, Me), 3.97–4.13 (2H, (AB)X3 system, 3JAX = 7.2, JBX
=
3
7.2, 2JAB = 12.2, CH2O), 4.28 (2H, q, 3JHH = 7.2, CH2O), 7.16 (1 H, s, CH), 7.30–7.73 (8
H, m, 8 CH), 8.29 (1 H, s, NH). 13C NMR (75 MHz, CDCl3): δ = 14.2 (Me), 14.3 (Me),
21.5 (Me), 21.6 (Me), 62.0 (CH2O), 63.3 (CH2O), 74.2 (C), 127.7 (2 CH), 127.9 (2 CH),
129.3 (2 CH), 129.4 (2 CH), 129.5 (CH), 131.3 (CH), 131.4 (C), 132.5 (CH), 137.4 (C),
138.5 (C), 161.8 (COO), 162.6 (COO), 171.8 (C N), 180.5 (C S).
REFERENCES
1. R. Kumar and S. C. M. Prem, Tetrahedron Lett., 49, 5475 (2008).
2. C.-K. Cheng, J. Wu, Y. Liu, T.-S. Lee, S.-J. Kang, M.-T. Sheu, and W.-S. Lee, Vascular Phar-
macology, 48, 138 (2008).
3. Y. Liu, J. Wu, P.-Y. Ho, L.-C. Chen, C.-T. Chen, Y.-C. Liang, C.-K. Cheng, and W.-S. Lee,
Cancer Lett., 271, 294 (2008) .
4. I. Yavari and N. Zabarjad-Shiraz, Monatsh. Chem., 134, 445 (2003).
5. I.Yavari and N. Zabarjad-Shiraz, Phosphorus, Sulfur, and Silicon, 179, 1477 (2004).
6. I. Yavari, N. Zabarjad-Shiraz, M. T. Maghsoodlou, and N. Hazeri, Phosphorus, Sulfur, Silicon,
177, 759 (2002).
7. I. Yavari and L. Ahmadian-Razlighi, Phosphorus, Sulfur, and Silicon, 181, 771 (2006).
8. I. Yavari and N. Zabarjad-Shiraz, Phosphorus, Sulfur, and Silicon, 176, 141 (2006).
9. I. Yavari and F. Feiz-Javadian, Phosphorus, Sulfur, and Silicon, 181, 1011 (2006).
10. I. Yavari and E. Karimi, Phosphorus, Sulfur, and Silicon, 182, 595 (2007).
11. K. C. Nicolaou, M. W. Harter, J. L. Gunzner, and A. Nadin, Liebigs Ann., 1283 (1997).
12. F. A. L. Anet and R. Anet, In Dynamic Nuclear Magnetic Resonance Spectroscopy, F. A. Cotton
and L. M. Jackman, eds. (Academic Press, New York, 1975), p 543.
13. J. Safari, H. Naeimi, M. M. Ghanbari, and O. Sabzi-Fini, Russ. J. Org. Chem., 45, 477 (2009).