Highly efficient dehydrogenation of 5-benzyl-3-phenyl-2-thioxoimidazolidin- 4-one: Microwave versus flash vacuum pyrolysis conditions

Article abstract of DOI:10.1002/ejoc.201200257

5-Benzyl-3-phenyl-2-thioxoimidazolidin-4-one underwent thermal dehydrogenation to afford 5-benzylidene-2-thioxoimidaxolidin-4-one under microwave and flash vacuum pyrolysis conditions. A high predominance of the Z-isomer over the E-isomer of the imidazolidinone product was achieved. By using DFT and NBO calculations, the mechanism of the dehydrogenation and the selectivity were also explored. In this article we report the dehydrogenation reaction of a benzylthioxoimidazolidinone derivative by using two unconventional and solvent-free methodologies: flash vacuum pyrolysis and microwave-induced pyrolysis. DFT calculations were performed to understand the dehydrogenation mechanism and to explain the high selectivity achieved towards the formation of the Z-isomer.

Full text of DOI:10.1002/ejoc.201200257

FULL PAPER
DOI: 10.1002/ejoc.201200257
Highly Efficient Dehydrogenation of 5-Benzyl-3-phenyl-2-thioxoimidazolidin-
4-one: Microwave versus Flash Vacuum Pyrolysis Conditions
Ana J. Pepino,[a] Walter J. Peláez,[a] Elizabeth L. Moyano,*[b] and Gustavo A. Argüello*[a]
Keywords: Dehydrogenation / Flash pyrolysis / Microwave chemistry / Reaction mechanisms
5-Benzyl-3-phenyl-2-thioxoimidazolidin-4-one
underwent
the E-isomer of the imidazolidinone product was achieved.
thermal dehydrogenation to afford 5-benzylidene-2-thioxo- By using DFT and NBO calculations, the mechanism of the
imidaxolidin-4-one under microwave and flash vacuum pyr-
dehydrogenation and the selectivity were also explored.
olysis conditions. A high predominance of the Z-isomer over
to produce this type of dehydrogenation. Furthermore, this
process is usually nonselective, involves high temperatures,
and long reaction times favoring thermal cracking of the
reaction mixture into lighter compounds and coke.
Introduction
Pharmaceutically active compounds such as antimyco-
bacterials,[1] immunomodulators,[2] anticonvulsivants,[3] and
antifungals[4] that present the 5-arylmethylene-2-thioxo-
imidazolidin-4-one nucleus have been a motivating factor
for developing improved methods for their synthesis and
examination of their reactivity. However, these methodolo-
gies usually involve several steps that inevitably lead to im-
portant decreases in the global yield of the reaction. As an
example of a current method applying these multiple-step
procedures, we can mention the recent work by Parwal et
al., where a multicomponent reaction including benzalde-
hydes, glycine, and thiocyanate was reported.[5]
In pursuing better reaction conditions and greener ap-
proaches to what has previously been reported, hereby we
report two efficient ecofriendly methodologies (solventless
reaction conditions) to synthesize the 5-phenylmethylene-2-
thioxoimidazolidin-4-one core through a selective dehydro-
genation reaction on 5-benzyl-3-phenyl-2-thioxoimid-
azolidin-4-one (3) that also provides a remarkable specific-
ity to the synthesis of the Z-isomer of the main product. 5-
Benzyl-2-thioxoimidazolidin-4-ones structurally differ from
the 5-phenylmethylene-2-thioxoimidazolidin-4-ones target
in the presence of an exocyclic double bond at C5. Many
reactions have been proposed to induce the formation of
the exocyclic double bonds through dehydrogenation reac-
tions in heterocyclic systems. In most cases, the use of a co-
reactant or a catalyst, such as rhodium,[6] iridium,[7] or even
the more complex catalyst like Cr-MCM-41,[8] is required
In this work, we report the application of microwave-
induced pyrolysis (MIP) and flash vacuum pyrolysis (FVP)
procedures to carry out the selective dehydrogenation of 5-
benzyl-3-phenyl-2-thioxoimidazolidin-4-one (3) to obtain
phenylmethylene-3-phenyl-2-thioxoimidazolidin-4-one (4)
without any additives or catalysts. Dehydrogenations are
quite common in high-temperature pyrolysis, especially in
the final step in a sequence leading to the formation of an
aromatic or stable product.[9] However, information regard-
ing selective dehydrogenations is scarce and few examples
have been studied. In our case, an extremely high specificity
(98:2) on the Z/E isomer distribution of 4 was achieved,
and a feasible mechanism for the dehydrogenation is hereby
proposed based on results fully supported by DFT calcula-
tions.
On the other hand, microwave-assisted reactions are in-
variably faster and often proceed in higher yields than those
performed under conventional thermal methods.[10] It has
been reported that with high initial powers (150–300 W),
solid-phase reactions carried out under microwave irradia-
tion produce results that are similar to FVP due to the high
heating rates.[11] To extend the range of FVP and microwave
applications we have compared both methodologies in the
dehydrogenation process of thioxoimidazolidinone 3.
Results and Discussion
[a] INFIQC-Depto de Fisicoquímica,
Facultad de Ciencias Químicas, UNC,
Córdoba, CP5000, Argentina
[b] INFIQC-Depto de Química Orgánica,
Facultad de Ciencias Químicas, UNC,
Córdoba, CP5000, Argentina
The selection of starting material 3 was important be-
cause it dehydrogenates to give thioxoimidazolidinone 4.
Synthesis of 3 was described previously from phenyl iso-
thiocyanate (1) and phenylalanine (2) in a 1 n aqueous solu-
tion of hydrogen chloride in good yields (80%).[12] Instead
of using the traditional protocol, we chose an ecofriendly
Fax: +54-351-433-4170
E-mail: lauramoy@fcq.unc.edu.ar
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201200257.
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Eur. J. Org. Chem. 2012, 3424–3430

Dehydrogenation of 5-Benzyl-3-phenyl-2-thioxoimidazolidin-4-one
Scheme 1. MIP and FVP reactions of thioxoimidazolinone 3.
methodology without the use of a solvent and application
In addition, fragmentation of the thioxoimidazolidinone
of microwave irradiation as a heating source to prepare this ring also occurred, and compounds 1, 5, and 6 were ob-
precursor. Thus, moderate to good yields of 3 (60–80%) tained in the reaction mixture (Scheme 1). Aniline 6 could
were achieved while avoiding a cumbersome synthesis (see be rationalized through the formation of nitrene species
the Experimental Section).
capturing hydrogen. The formation of 2-phenylbenzimid-
In the next step, compound 3 was subjected to MIP at azole (5) is less clear, as it would involve several steps com-
300 W in a sealed tube in the presence of different solvents bining highly reactive intermediates coming from the de-
as well as under solvent-free conditions at 200 and 250 °C. composition of 3.
Reactions below 200 °C were carried out without success,
Then, FVP of 3 was performed at temperatures between
and only the starting material was recovered. From 200 °C, 300 and 450 °C at 10–2 Torr, and contact times of 10–2 s.
the main product was 5-benzylidene-3-phenyl-2-thioxoimid- Thioxoimidazolidinone 4 was the main product obtained
azolidin-4-one (4), which was obtained through dehydroge- (as a mixture of Z/E-isomers) at all evaluated temperatures
nation of 3 (Scheme 1). Dimethylformamide (DMF), nitro- (Table 2), which is similar to the results obtained in the mi-
methane (NM), and o-dichlorobenzene (o-DCB) were crowave-assisted reactions. It should be noted that over
evaluated as solvents. However, better yields (42–47%) were 400 °C, the pyrolyzate showed trace amounts of products 1,
achieved under solvent-free conditions after 25 min of irra- and 7–9. However, acceptable yields of 4 could be obtained
diation at 250 °C. The results are summarized in Table 1. It without significant formation of secondary or carbon-
is important to remark that compound 4 was obtained as aceous products at 450 °C.
1
a mixture of Z/E isomers under all conditions. H NMR
spectroscopic analysis of this mixture indicated that the Z/E
ratio was 98:2 and remained unchanged under all reaction
conditions.
Table 2. FVP reactions of 3.
T
% Yield[a]
[°C]
3
4
7
8
9
300
325
350
78
70
64
51
40
16
22
30
36
–
–
–
–
–
3
–
–
–
–
–
2
–
–
–
Table 1. MW reactions of 3.
T
[°C]
Solvent
Time
[min]
% Yield[a]
375
49
–
traces
5
1
3
4[b]
5
6
400[b]
55
450[c]
71(60)[d]
200
200
200
200
DMF
NM
o-DCB
–
1
1
1
5
10
15
20
25
5
33
3
4
6
9
8
9
15
17
18
21
21
21
18
92
91
86
79
78
67
47
46
31
10
8
20
3
4
2
3
9
1
1
0
0
0
1
1
1
2
3
3
4
20
1
0
6
9
[a] Percentage determined by 1H NMR spectroscopy. [b] Trace
amounts of product 1 were detected. [c] The presence of coke was
detected. [d] Isolated yield.
5
9
13
20
14
29
42
46
47
11
18
23
20
23
22
22
The formation of imidazolone 7 can be rationalized by
the loss of sulfur from 4; this type of elimination is a pre-
dominant process in the thermolysis of thioxoderivatives.[13]
Imidazoindolone 8 can be formed by intramolecular cycli-
zation of thioxoimidazolidinone 4 involving an additional
dehydrogenation reaction. A similar cyclization was ob-
served in the transformation of anilinopyridines in a con-
250
–
10
15
20
25
7
[a] Determined by GC–MS. [b] Mixture of Z/E isomers (98:2).
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A. J. Pepino, W. J. Peláez, E. L. Moyano, G. A. Argüello
FULL PAPER
tinuous-flow reactor containing K-16 as a dehydrogenating ines,[20] and β-elimination of CO2 from pyruvic acid,[21] are
catalyst at 560–580 °C,[14] and other similar processes can nice examples of thermal processes with a concerted charac-
be achieved in the presence of lead(IV) oxide.[15]
ter.
To address the origin of compounds 7 and 8, FVP reac-
Thus, kinetic measurements on the FVP of 3 were carried
tions of 4 at 450 °C were performed. Thus, products 1, 7, out to get more information on the reaction mechanism (see
and 8 were obtained in low yields (2–4%), confirming our Table 3). Thioxoimidazolidinone 3 was the only starting
previous assumption and also showing the high thermal material that afforded 4 without decomposition to other by-
stability of 4 (85% was recovered). Further, no change in products at lower reaction temperatures (300–400 °C). Re-
the isomer ratio of 4 was observed after the gas thermolysis. action constants were measured at each temperature by at
Although in FVP systems many products were formed, the least three determinations. Not only the relative concentra-
yield of desired imidazolidinone 4 was slightly better than tions of the starting material but also the concentrations of
1
that achieved in MW-assisted reactions.
product were determined by H NMR spectroscopy. Reac-
The main goal of this contribution was the study of the tion times were calculated as V0/m (contact time), where V0
dehydrogenation mechanism to give imidazolidinone 4. is the volume of the reaction tube inside the hot zone and
Therefore, it became very important to acknowledge that m is the carrier gas flow. Arrhenius parameters were calcu-
precursor 3 can be present in tautomeric equilibrium and, lated by using the classical equation (lnk vs. 1/T). To vali-
therefore, the mechanism would strongly depend on which date the system, the kinetic parameters for the pyrolysis of
tautomer is reacting. In addition, this kind of mechanistic ethyl acetate were measured and compared with those re-
information can be better retrieved through the use of FVP ported for a static system; these results, together with a de-
techniques to obtain kinetic and thermodynamic param- tailed description of the methodology, were exhaustively de-
eters.[16]
scribed earlier.[22] From the results in Table 3, the calculated
There are no previous mechanistic studies on the gas- negative value of ΔS# (–34.8 eu) indicated that the mecha-
phase dehydrogenation of benzylimidazolidinones. We sug- nism greatly differed from the expected radical process,
gest two main ways of analyzing the mechanism: a stepwise where this value should have been positive. Thus, the dehy-
manner via a radical intermediate (Scheme 2, paths A and drogenation reaction could be taking place through one of
B) and a concerted route (Scheme 2, paths C–F). Regarding the concerted mechanisms described in Scheme 2.
all the possible reaction mechanisms, radical mechanisms
Despite this experimental result, all paths proposed in
were expected to give positive entropies of activation, as Scheme 2 were studied by quantum chemistry calculations
previously reported;[17,18] on the other hand, concerted to obtain further information about the reaction mecha-
ways were expected to give negative values. Several reac- nism. The optimized geometries of reactant 3 and products
tions, such as ring opening of hexahydroquinazolinones,[19] 4Z and 4E are shown in Figure 1. The calculated energy
isomerization of angular to linear fused triazolobenzotriaz- difference values were 24.0 and 26.4 kcalmol–1 for 4Z and
Scheme 2. Proposed mechanisms for the dehydrogenation of thioxoimidazolinone 3.
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Dehydrogenation of 5-Benzyl-3-phenyl-2-thioxoimidazolidin-4-one
Table 3. Arrhenius parameters for the dehydrogenation reaction of
3.
Regarding the proposed concerted hydrogen elimi-
nations, paths C and D involve direct loss of H2 through
four-centered transition states TS-c and TS-a, respectively.
Path C affords 4 in one step, whereas path D leads first to
the formation of intermediate I-d, which later can tauto-
merize into 4 through TS-b. The energy barrier for path C is
110 kcalmol–1, whereas path D requires 105 kcalmol–1 for
hydrogen elimination and 57 kcalmol–1 for tautomeri-
zation. Both paths C and D need almost 20 kcalmol–1 more
than the radical processes.
T
[°C]
C/C0
Contact
k [10–2 s][a]
Ea
ΔS#
[eu]
time [10–2 s]
[kcalmol–1]
300
325
350
375
400
0.78Ϯ0.02 1.08Ϯ0.07 0.23Ϯ0.01 11.2Ϯ0.6 –34.8Ϯ0.4
0.70Ϯ0.02 1.03Ϯ0.06 0.35Ϯ0.02
0.64Ϯ0.02 0.99Ϯ0.06 0.45Ϯ0.02
0.51Ϯ0.02 0.95Ϯ0.05 0.71Ϯ0.03
0.40Ϯ0.01 0.92Ϯ0.05 1.00Ϯ0.05
[a] Values averaged over at least three determinations.
It is known that imidazolidinones like 3 can exist in dif-
ferent tautomeric forms depending on the medium.[23] For
that reason, dehydrogenation from intermediates enol I-e
and thioenol I-g was calculated (paths E and F, which in-
volve tautomerization followed by H2 elimination through
a six-membered transition state). Thus, in path E, tauto-
merization to enolic form I-e (TS-d: 80.4 kcalmol–1) was
proposed. This intermediate can either directly eliminate H2
to afford 4 (EǞEi, TS-e: 50.0 kcalmol–1) or tautomerize to
thiol form I-f (EǞEii, TS-f: 72.0 kcalmol–1). In both cases,
the higher energy step was the enolization to I-e.
4E, respectively. Thus, 4E was less stable by 2.4 kcalmol–1
than 4Z. Radical pathways (Scheme 2, paths A and B)
should involve a double elimination of hydrogen atoms in
stages through intermediacy of species I-a, I-b, and I-c.
DFT calculations revealed that the first step was a unimo-
lecular dissociation reaction, where the potential energy
raised monotonically.
Path F involves the conversion of 3 into thioenol form
I-g (TS-h: 41.2 kcalmol–1) followed by a new tautomeri-
zation (EǞEii), which ends up with the same intermediate
I-f (TS-i: 72.3 kcal mol–1). Nevertheless, the energy required
for this path was almost 10 kcalmol–1 lower than that in-
volved in path E. From intermediate I-f, dehydrogenation
was possible (TS-g: 45.0 kcalmol–1) and required
5 kcalmol–1 less energy than that estimated for path EǞEi.
In summary, from all the calculations, we propose that
the lowest channel for the dehydrogenation reaction of
compound 3 is path F, which is the enolization rate-de-
termining step that gives I-f. Nevertheless, the absolute val-
ues found in this study were considerably different to those
found experimentally.
Figure 1. Optimized geometries of 3 and 4.
On the basis of steric and electrostatic factors, calcula-
tions showed that the bulky phenyl ring would not have an
influence on the experimentally observed Z/E ratio. Thus,
it was not possible to explain why high selectivity was ob-
served (98:2) on these terms. There are no records in the
literature for that particular selectivity, though there is a
significant number of articles reporting the existence of
both types of isomers.[24,25] Our experimental results
showed that the ratio of isomers of 4 remained the same,
irrespective of the methodology employed, namely, MIP or
FVP. Therefore, we believe that the explanation, supported
by calculations on specific NBO donor–acceptor interac-
tions, lies before the final product was formed but after the
rate-determining step, that is, during the formation of the
In the proposed path A, the elimination of either one of
both hydrogen atoms affords benzyl radicals I-a and I-b.
The energies required were 96.5 and 94.8 kcalmol–1, respec-
tively (see Table 4), whereas in the case of path B, dissoci-
ation could lead to the formation of heterocyclic radical I-
c and the energy considered necessary was 91.6 kcalmol–1.
It is important to note that any of the radicals formed
should allow free rotation of either the phenyl or benzyl
group, and therefore, the next hydrogen elimination would
initially lead to the formation of 4Z and 4E isomers in
equal proportions. The measured values of ΔG# and ΔS#
could not be supported by these radical processes and they
were accordingly discarded as outlined mechanisms of the
dehydrogenation reaction.
Table 4. B3LYP energy of transient species in the gas phase.
Path
Radical pathways Concerted pathways
A
B
C
D
E
F
Species
I-a
94.8
I-b
96.5
I-c TS-c[b] TS-a[b] I-d TS-b[c] TS-d[c] I-e TS-e[b] TS-f[c] TS-h[c]
91.6 110.0 105.0 42.8 57.4 80.4 17.8 50.0 72.0 41.2
I-g TS-i[c] I-f TS-g[b] I-h
TS-j[c]
15.3
ΔE[a]
16.1 72.3
28.4 45.0
41.2
[a] Values in kcalmol–1. [b] Hydrogen elimination. [c] Tautomerization.
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A. J. Pepino, W. J. Peláez, E. L. Moyano, G. A. Argüello
FULL PAPER
vice. Oxygen-free dry nitrogen was used as the carrier gas. Contact
times were around 10–2 s and a pressure of 0.02 Torr was used.
Products were trapped at liquid air temperature, extracted with a
solvent, and subjected to different analyses or separation tech-
niques. In all FVP experiments, the recovery of material was
Ͼ90%. Reactions under microwave irradiation were performed in
cylindrical quartz tubes (Φ = 1.5 cm) located in a CEM microwave
reactor (2.455 GHz), with adjustable power within the range 0–
300 W and a wave guide (monomode) fitted with a stirring device
and an IR temperature detector. Melting points were determined
with an Electrothermal 9100 melting point apparatus. All com-
pounds were characterized by standard spectroscopic techniques
(1H NMR, 13C NMR, HMBC, HSQC, UV, IR) and mass spec-
trometry, and all data are in agreement with the proposed struc-
transition state that led to the very dehydrogenation step.
The NBO data showed that there were effective energy in-
teractions between the O17 oxygen lone pair of electrons as
well as the C12 antibonding lone pair of electrons, both
with the σ antibonding orbital (σ*) of H13–H18 favoring
the formation of the TS-gZ isomer by about 10 kcalmol–1
(see Figure 2).
1
tures. H, 13C, HSQC and HMBC spectra were recorded in [D6]-
DMSO and [D6]acetone with a Bruker Avance II 400 MHz spec-
trometer (BBI probe, z gradient) (1H at 400.16 MHz and 13C at
100.56 MHz). Chemical shifts are reported in parts per million
(ppm) downfield from TMS. The spectra were measured at 22 °C.
Absorption spectra of the solution was recorded with a UV-1601
Shimadzu spectrophotometer using a quartz cell with an optical
path length of 1 cm and acetonitrile as solvent. Infrared solid spec-
tra were recorded with an FTIR Bruker IFS 28v spectrometer, with
a resolution of 2 cm–1 in the range from 4000 to 400 cm–1 by using
KBr disks. All calculations were performed with the Gaussian03
program system[26] by using a DFT-B3LYP/6-31+G(d,p) approach.
Transition-state theory was used to evaluate the energy of the dif-
ferent channels. The transition states were characterized by the
presence of one negative frequency and the internal reactionЈs co-
ordinate (IRC) method was applied to verify that the correct states
were connected. Though we knew that more precise methods were
available, we had a compromise between the size of the molecules
under study and the computational cost. Gas chromatography/
mass spectrometry (GC/MS) analyses were performed with a Shim-
adzu GC–MS-QP 5050 spectrometer equipped with a VF column
(30 mϫ0.25 mmϫ5 μ) by using helium as eluent at a flow rate of
1.1 mLmin–1. The injector and ion source temperature was 280 °C,
the oven heating ramp was 15 °Cmin–1 from 150 up to 280 °C,
and the interface temperature was 280 °C. The pressure in the MS
instrument was 10–5 Torr, precluding ion-molecule reactions from
taking place, and MS recordings were made in the electron impact
mode (EI) at ionization energy of 70 eV. In particular, the structure
of compound 4Z was unambiguously determined through single-
crystal X-ray diffraction analysis by using a Bruker SMART APEX
CCD diffractometer (see the Supporting Information).
Figure 2. Atom numbering for TS-gZ and TS-gE.
Despite the fact that the experimental energy barrier ob-
tained was much lower than the calculated numbers, we be-
lieve that the overall trend of the calculations was quite sig-
nificant, because we can not only explain the products but
also justify the high selectivity.
Conclusions
A high selective synthesis of Z-5-phenylmethylene-2-thi-
oxoimidazolidin-4-one (4) was nicely carried out by dehy-
drogenation of imidazolidinone 3. We have developed two
efficient routes toward the target compound: microwave-in-
duce pyrolysis (MIP) and flash vacuum pyrolysis (FVP). In
the case of the FVP reactions, yields were better than those
obtained in the MW experiments.
General Procedures for the Synthesis of Thioxoimidazolidinone 3:
This compound was prepared by modification of a previously re-
ported methodology[12] using two procedures:
According to theoretical calculations, we fully rationalize
and suggest that dehydrogenation can be achieved in a con-
certed way involving a thio-enol intermediate (i.e., I-f). In
addition, the experimentally observed selectivity can arise
from orbital interactions between the O17–C12 atoms be-
fore the formal dehydrogenation takes place.
Method A: Phenyl isothiocyanate (1; 0.446 g, 3.3 mmol) was added
to l-phenylalanine (2; 0.496 g, 3.0 mmol) suspended in a mixture
of water/acetone (1:1, 30 mL). Then, freshly powdered NaOH
(0.120 g) was added. The mixture was heated at reflux 2 h and left
to stand overnight. Crystalline product 3 was isolated by vacuum
filtration, washed with water, and dried (60% yield).
This work strongly increases the interest of dehydrogena-
tion studies of other heterocyclic compounds using MIP
and FVP as alternative synthetic tools.
Method B: In a cylindrical quartz tube, l-phenylalanine (2; 0.496 g,
3.0 mmol) and phenyl isothiocyanate (1; 0.446 g, 3.3 mmol) were
placed in that order. Nitromethane (0.3 mL) was added only to
homogenize the mixture to perform the reaction. Then, the tube
was introduced into the CEM microwave reactor. The mixture was
stirred at room temperature and then irradiated at 150 °C for
10 min. The reaction crude was extracted with ethyl acetate
(3ϫ15 mL), the organic layer was dried with anhydrous Mg2SO4,
Experimental Section
General Methods: FVP reactions were carried out in a Vycor glass
reactor by using a tube furnace with a temperature-controller de-
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Dehydrogenation of 5-Benzyl-3-phenyl-2-thioxoimidazolidin-4-one
and after removal of the solvent under reduced pressure the solid
was recrystallized (acetone/water) to give pure thioxoimidazolinone
3 (78.5% yield).
Supporting Information (see footnote on the first page of this arti-
cle): Characterization of compounds 1 and 3–9 and computational
calculations.
5-Benzyl-3-phenyl-2-thioxoimidazolidin-4-one (3): M.p. 187–188 °C
1
(ref.[12] 187 °C). H NMR (400.16 MHz, [D6]DMSO): δ = 3.12 (d,
J = 4.4 Hz, 2 H); 4.78 (m, 1 H), 6.78 (dd, J = 7.9, 2.0 Hz, 2 H),
7.21 (dd, J = 7.9, 2.0 Hz, 2 H), 7.30 (m, 3 H), 7.38 (m, 3 H), 10.61
(br. s, 1 H) ppm. 13C NMR (100.56 MHz, [D6]DMSO): δ = 36.6,
60.6, 127.5, 128.6 (2 C), 128.9 (2 C), 129.0, 129.1 (2 C), 130.2 (2
C), 133.6, 134.9, 173.9, 182.7 ppm. GC–MS: t = 16.61 min. MS
Acknowledgments
Authors thank Consejo Nacional de Investigaciones Científicas y
Técnicas (CONICET) and Secretaría de Ciencia y Tecnología –
Universidad Nacional de Córdoba (SECyT-UNC) for financial
support. They also thank Prof. Cecilio Álvarez Toledano (Instituto
de Química, Universidad Nacional Autónoma de México, México)
for crystallographic analysis of compound 4z.
(EI): m/z (%) = 282 (34) [M]+. IR (KBr): ν = 3157 (NH st), 2903
˜
(C–H sp3 st), 1750 (C=O st), 1252 (C=S st) cm–1. UV/Vis
(CH3CN): λ (εϫ104, m–1 cm–1) = 269 (1.654Ϯ0.006) nm.
General Procedures for the Synthesis of Thioxoimidazolidinone Iso-
mers 4Z and 4E
Microwave Irradiation: A cylindrical quartz tube (Φ = 1.5 cm) was
charged with 2-thioxoimidazolidin-4-one (3; 25 mg, 88.5 μmol). Af-
ter introduction into the CEM microwave reactor, it was irradiated
at 200 and 250 °C between 5 and 25 min (Table 3). The mixture
was extracted with acetone and subjected to GC–MS analysis.
Then, the crude was purified by preparative thin-layer chromatog-
raphy (dichloromethane/hexane, 6:4) as solvent mixture to afford
title compound 4 in moderate yield (35–40%).
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Compounds 1, 6, and 9 were characterized by comparison with
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Z-5-Benzylidene-3-phenyl-2-thioxoimidazolidin-4-one (4Z): M.p.
1
208–209 °C (1-hexanol). H NMR (400.16 MHz, [D6]DMSO): δ =
6.70 (s, 1 H), 7.38–7.56 (m, 8 H), 7.33 (d, J = 6.9 Hz, 2 H), 12.60
(br. s, 1 H) ppm. 13C NMR (100.56 MHz, [D6]DMSO): δ = 113.3,
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132.8, 133.8, 164.4, 179.2 ppm. GC–MS: t = 19.98 min. MS (EI):
m/z (%) = 280 (100) [M]+. IR (KBr): ν = 3213 (N–H st), 1743 (C=O
˜
st), 1252 (C=S st) cm–1. UV/Vis (CH3CN): λ (εϫ104, m–1 cm–1) =
356 (3.30Ϯ0.01), 371 (3.21Ϯ0.01).
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E-5-Benzylidene-3-phenyl-2-thioxoimidazolidin-4-one (4E): This
compound was identified from a mixture with 4Z. 1H NMR
(400.16 MHz, [D6]DMSO): δ = 6.75 (s, 1 H), 7.38–7.56 (m, 8 H),
8.04 (dd, J = 7.8, 3.9 Hz, 2 H); 12.55 (br. s, 1 H) ppm. 13C NMR
(100.56 MHz, [D6]DMSO): δ = 120.1, 126.9, 128.9, 129.2, 129.3 (4
C, br. s.), 130.1 (2 C), 131.0 (2 C), 132.9, 133.7, 161.8, 175.9 ppm.
GC–MS: t = 20.73 min. MS (EI): m/z (%) = 280 (100) [M]+.
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2-Phenyl-1H-benzo[d]imidazole (5): This compound was identified
by GC–MS analysis with Ͼ90% match with the NIST library[27]
GC–MS: t = 8.39 min. MS (EI): m/z (%) = 194 (100) [M]+.
Z-4-Benzylidene-1-phenyl-1H-imidazol-5-one (7): This compound
was identified by GC–MS analysis, t = 14.83 min. MS (EI): m/z
(%) = 248 (57) [M]+.
2-Phenyl-3-thioxo-2,3-dihydro-1H-imidazo[1,5-a]indol-1-one
(8):
This compound was identified by GC–MS: t = 17.81 min. MS (EI):
m/z (%) = 278 (47) [M]+.
1,2-Diphenylethane (9): This compound was characterized by com-
parison with authentic sample. GC–MS: t = 5.94 min. MS (EI):
m/z (%) = 182 (27) [M]+.
Eur. J. Org. Chem. 2012, 3424–3430
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3429

A. J. Pepino, W. J. Peláez, E. L. Moyano, G. A. Argüello
FULL PAPER
Rega, G. A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K.
Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y.
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[27] http://webbook.nist.gov.
Received: March 2, 2012
Published Online: May 16, 2012
3430
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© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 3424–3430