Synthesis of isomeric 3-phenyl-5-(pyridylmethylene)-2-thiohydantoins and their S-methylated derivatives. Molecular and crystal structures of (5Z)-3-phenyl-5-(pyridin-2-ylmethylene)-2-thiohydantoin and (5Z)-2-methylthio-3- phenyl-5-(pyridin-2-ylmethylene)-

Article abstract of DOI:10.1007/s11172-005-0201-z

Three procedures were used for the synthesis of α-, β, and γ-pyridyl-substituted (5Z)-3-phenyl-5-(pyridylmethylene)-2-thiohydantoins: the reaction of 2-thiohydantoin with the corresponding aldehyde in AcOH in the presence of AcONa, the two-step one-pot sy

Full text of DOI:10.1007/s11172-005-0201-z

2850
Russian Chemical Bulletin, International Edition, Vol. 53, No. 12, pp. 2850—2855, December, 2004
Synthesis of isomeric 3ꢀphenylꢀ5ꢀ(pyridylmethylene)ꢀ2ꢀthiohydantoins
and their Sꢀmethylated derivatives. Molecular and crystal structures
of (5Z )ꢀ3ꢀphenylꢀ5ꢀ(pyridinꢀ2ꢀylmethylene)ꢀ2ꢀthiohydantoin
and (5Z )ꢀ2ꢀmethylthioꢀ3ꢀphenylꢀ5ꢀ(pyridinꢀ2ꢀylmethylene)ꢀ
3,5ꢀdihydroꢀ4Hꢀimidazolꢀ4ꢀone
A. G. Majouga, E. K. Beloglazkina,ꢀ S. Z. Vatsadze, N. A. Frolova, and N. V. Zyk
Department of Chemistry, M. V. Lomonosov Moscow State University,
Leninskie Gory, 119992 Moscow, Russian Federation.
Fax: +7 (095) 939 0290. Eꢀmail: bel@org.chem.msu.su
Three procedures were used for the synthesis of αꢀ, βꢀ, and γꢀpyridylꢀsubstituted
(5Z )ꢀ3ꢀphenylꢀ5ꢀ(pyridylmethylene)ꢀ2ꢀthiohydantoins: the reaction of 2ꢀthiohydantoin with
the corresponding aldehyde in AcOH in the presence of AcONa, the twoꢀstep oneꢀpot syntheꢀ
sis with the use of the same starting compounds, and threeꢀcomponent condensation of aryl
isothiocyanate, glycine, and aldehyde in AcOH. Alkylation of the resulting thiohydantoins
with iodomethane in the presence of a base afforded the corresponding Sꢀmethylated derivaꢀ
tives, viz., 2ꢀmethylthioꢀ3ꢀphenylꢀ5ꢀ(pyridylmethylene)ꢀ3,5ꢀdihydroꢀ4Hꢀimidazolꢀ4ꢀones.
The structures of (5Z )ꢀ3ꢀphenylꢀ5ꢀ(pyridinꢀ2ꢀylmethylene)ꢀ2ꢀthioxoimidazolinꢀ4ꢀone and
(5Z )ꢀ2ꢀmethylthioꢀ3ꢀphenylꢀ5ꢀ(pyridinꢀ2ꢀylmethylene)ꢀ3,5ꢀdihydroꢀ4Hꢀimidazolꢀ4ꢀone were
established by Xꢀray diffraction analysis.
Key words: thiohydantoins, 2ꢀalkylthioꢀ3,5ꢀdihydroimidazolones, condensation, pyridineꢀ
carboxaldehydes, Sꢀalkylation, crystal and molecular structure.
2ꢀThiohydantoins (4ꢀoxoimidazolidineꢀ2ꢀthiones)
pare chelate complexes in which coordination occurs
through the N atom of the thiohydantoin ring and
the electronꢀdonating atom of the substituent at posiꢀ
tion 5.19—21 For example, the reaction of N(3)ꢀunsubꢀ
stituted 5ꢀ(2ꢀpyridylmethylene)hydantoin with copper(II)
chloride affords a supramolecular complex, in which two
N atoms form a chelate coordination bond with the CuII
ions and the organic fragments are linked through hydroꢀ
gen bonds.19 These systems are of considerable interest,
because a transition metal ion introduced into supramoꢀ
lecular crystalline systems imparts the optical, conductꢀ
ing, and magnetic properties to these compounds, due to
which such materials hold promise as conductors and
ferromagnets in nonlinear optics.
and their Sꢀalkylated derivatives (2ꢀalkylthioꢀ3,5ꢀdihydroꢀ
4Hꢀimidazolꢀ4ꢀones) have attracted attention as conveꢀ
nient synthetic intermediates containing both electrophilic
and nucleophilic C atoms and also because these comꢀ
pounds have a broad spectrum of biological activities.
The hydantoin and thiohydantoin fragments are responꢀ
sible for antiarrhythmic1 and antihypertensive2,3 activiꢀ
ties. In addition, thiohydantoins have found application
as fungicides and herbicides.4 Due to the presence of the
nucleophilic C atom at position 5 of the thiohydantoin
ring, various substituents can be introduced at this posiꢀ
tion, and 5ꢀsubstituted thiohydantoins are also used in
therapeutic practice.5—14
In many cases, coordination of sulfurꢀ and nitrogenꢀ
containing compounds to transition metal ions enhances
their antiviral and antitumor activities.15 From this point
of view, 2ꢀthiohydantoins and their Sꢀalkylated derivaꢀ
tives, which contain endoꢀ and exocyclic donor atoms of
various nature and can exist as either neutral molecules or
monoanions,16—18 are of interest as ligands for the prepaꢀ
ration of metal chelate complexes. The introduction of
substituents containing additional donor atoms at posiꢀ
tion 5 of the thiohydantoin ring makes it possible to preꢀ
In the present study, we synthesized 5ꢀpyridylꢀ
methyleneꢀsubstituted thiohydantoins 1a—c and their
Sꢀalkylated analogs 2a—c and investigated their strucꢀ
tures (Scheme 1).
Thioꢀsubstituted imidazolones and imidazolinones
containing the pyridine fragment have attracted our inꢀ
terest primarily in relation to coordination chemistry of
such compounds. Compounds 1a and 2a containing the
αꢀpyridyl fragments are promising ligands for the prepaꢀ
ration of chelate complexes, in which the electronꢀdoꢀ
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2734—2739, December, 2004.
1066ꢀ5285/04/5312ꢀ2850 © 2004 Springer Science+Business Media, Inc.

2ꢀThiohydantoins and their Sꢀmethylation
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 12, December, 2004 2851
Scheme 1
1, 2: Ar = 2ꢀpyridyl (a), 3ꢀpyridyl (b), 4ꢀpyridyl (c)
Table 1. Yields of thiohydantoins 1a—c prepared according to
the methods A—C
nating N atoms of the pyridine and thiohydantoin rings
are involved in coordination. Compounds 1b,c and 2b,c
containing the βꢀ and γꢀpyridyl fragments are of interest
from the viewpoint of the synthesis of dimeric and polyꢀ
meric complexes. Both N atoms of the thiohydantoin
ligand and its S atom can coordinate a metal ion. It should
be noted that a few transition metal complexes with
thiohydantoins have been described in the literature (see
above), but the data on the ability of Sꢀalkylated thioꢀ
hydantoins to be involved in coordination are lacking.
Three procedures for the preparation of 5ꢀarylideneꢀ
2ꢀthiohydantoins have been documented (see Scheme 1).
The procedure A involves the reaction of 2ꢀthiohydantoin
with the corresponding aldehyde in acetic acid in the
presence of an equimolar amount of anhydrous sodium
acetate14 and works well with a large series of aromatic or
heteroaromatic aldehydes.
The procedure B is based on the twoꢀstep oneꢀpot
synthesis with the use of the same starting compounds. In
the first step, thiohydantoin reacts with aldehyde in the
presence of potassium hydroxide in anhydrous ethanol.
In the second step, the potassium salt of 5ꢀarylideneꢀ2ꢀ
mercaptoꢀ3,5ꢀdihydroꢀ4Hꢀimidazolꢀ4ꢀone is hydrolyzed
with dilute hydrochloric acid.14
Thiohydantoin
Yield of the target compound (%)
A
B
С
1а
1b
1c
Traces
50
75
95
7
11
Traces
61
60
It was found that different procedures of condensation
with pyridinecarboxaldehyde are optimal for particular
compounds 1a—c. For example, the methods A and C
are unsuitable for 2ꢀpyridinecarboxaldehyde, and the
method В proved to be the only preparative procedure for
the synthesis of 5ꢀ(pyridylmethylene)thiohydantoin 1a.
To the contrary, the method В is inapplicable for condenꢀ
sation with 3ꢀ and 4ꢀpyridinecarboxaldehydes because of
low yields of the target products. Unexpectedly, threeꢀ
component condensation (method C), which has been
considered earlier to be of little use, was not only as good
as other known methods as applied to the synthesis of
compound 1b but also affords arylidenethiohydantoin in
higher yields.
The procedure C involves threeꢀcomponent condenꢀ
sation of aryl isothiocyanate, glycine, and aldehyde in
acetic acid on heating. This method has been proposed
in 1950s, but it has found little practical use because of
low yields of the target compounds.22
In the present study, we examined the possibility of
using the methods A—C for the synthesis of 5ꢀpyridylꢀ
methyleneꢀsubstituted thiohydantoins 1a—c. The results
of this investigation are given in Table 1.
In the presence of substituents at both N atoms, conꢀ
densation of hydantoins with aromatic aldehydes proꢀ
duces two possible geometric isomers (Z and Е), whereas
condensation of unsubstituted hydantoin gives only the
Z isomer of 5ꢀbenzylidenehydantoin, which was acꢀ
counted for by isomerization through the tautomeric
equilibrium involving the proton transfer from the
N(1) atom.23 This signifies that the substituent at the
N(3) atom is not of decisive importance for geometric

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Majouga et al.
Table 2. Crystallographic data and details of the structure solution and refinement of compounds 1a and 2a
Parameter
1а
2а
Molecular formula
Molecular weight
C
15H11N3OS
281.33
C16H13N3OS
295.35
Color, habitus
Yellow prisms
Yellow platelets
Crystal dimensions/mm
0.5×0.3×0.3
0.72×0.35×0.08
Crystal system
Monoclinic
Monoclinic
Space group
P2(1)/n
Pbcm
a/Å
12.912(5)
8.486(2)
b/Å
6.552(4)
23.474(5)
c/Å
15.383(8)
7.2250(10)
α/deg
90
90
β/deg
94.57(4)
90
γ/deg
90
90
V/Å3
1297.3(11)
1439.2(5)
Z
4
4
Calculated density/g cm–3
Linear absorption coefficient/cm–1
F(000)
1.440
0.247
584
1.363
0.227
616
2.40—24.96
θ/deg
2.15—25.06
Reflection indices
–6 < h < 10, –7 < k < 7,
–18 < l < 18
4088
1982 (Rint = 0.0243)
1514
0 < h < 10, 0 < k < 27,
0 < l < 8
Number of measured reflections
Number of independent reflections
Number of reflections with I > 2σ(I )
Refinement variables
840
840 (Rint = 0.0000)
839
225
0.845
155
1.047
Goodnessꢀofꢀfit on F 2
R Factors based on reflections with I > 2σ(I )
R Factors based on all data
R1 = 0.0354, wR2 = 0.1008
R1 = 0.0613, wR2 = 0.1147
0.178/–0.201
R1 = 0.0300, wR2 = 0.0809
R1 = 0.0300, wR2 = 0.08
0.149/–0.158
Residual electron density/e•Å–3, ρmin/ρ
max
isomerism. However, it has earlier been demonstrated24
that condensation of aromatic aldehydes with 3ꢀmethylꢀ
thiohydantoin produces only (Z )ꢀ5ꢀbenzylidenethioꢀ
hydantoins, whereas condensation with 1ꢀmethylꢀ
hydantoin affords a mixture of both possible geometric
isomers. We isolated all three thiohydantoins 1a—c as one
isomer. The (Z ) configuration of compound 1a was unꢀ
ambiguously established by Xꢀray diffraction analysis.
2ꢀThiohydantoins were subjected to alkylation with
iodomethane in the presence of a base to prepare the correꢀ
sponding Sꢀmethylated derivatives 2a—c (see Scheme 1).
The molecular and crystal structure of compound 2a
was established by Xꢀray diffraction analysis.
Table 3. Selected interatomic distances (d) and bond angles (ω)
for compound 1а
Bond
d/Å
Angle
ω/deg
S(1)—C(9)
1.642(3)
C(9)—N(2)—C(7)
C(9)—N(3)—C(8)
N(2)—C(9)—S(1)
N(2)—C(7)—C(8)
N(3)—C(8)—C(7)
N(2)—C(9)—N(3) 105.5(2)
C(7)—C(6)—C(5)
C(7)—C(6)—H(6)
113.2(2)
N(2)—C(9) 1.358(3)
N(2)—C(7) 1.372(3)
N(3)—C(9) 1.399(3)
N(3)—C(8) 1.404(3)
C(7)—C(8) 1.481(3)
C(5)—C(6) 1.458(3)
C(6)—C(7) 1.346(3)
111.52(18)
127.18(19)
105.79(19)
104.0(2)
125.0(3)
116.3(14)
The crystallographic data and details of the structure
solution and refinement of compounds 1a and 2a are
given in Table 2. The selected bond lengths, bond angles,
and torsion angles in molecules 1a and 2a are listed in
Tables 3 and 4, respectively. The molecular structure of
1a is shown in Fig. 1, a. The thiohydantoin and pyridine
rings of molecule 1a are planar and virtually coplanar.
The plane of the benzene ring at the N(3) atom forms an
angle of 59° with the plane of the fiveꢀmembered ring of
the ligand. The fiveꢀmembered thiohydantoin ring shows
a pronounced tendency toward bond delocalization (all
bond lengths in the ring, except for the C(7)—C(8) bond
length,* are noticeably smaller than the average values).
The same is true for the C(6)—C(7) and C(5)—C(6)
bonds. The former bond is somewhat longer than the
standard C=C double bond, whereas the latter bond is,
correspondingly, shorter than the single bond. A similar
* Hereinafter, the atomic numbering scheme used in the discusꢀ
sion of the molecular and crystal structures of compounds 1a
and 2a and in Tables 2 and 3 corresponds to that presented
in Fig. 1.

2ꢀThiohydantoins and their Sꢀmethylation
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 12, December, 2004 2853
Table 4. Selected interatomic distances (d) and bond angles (ω)
for compound 2а
C(13)
a
b
C(13)
C(12)
C(11)
C(12)
C(11)
C(12A)
C(14)
C(15)
Bond
d/Å
Angle
ω/deg
C(11A)
C(10)
O
S(1)—C(1)
1.725(3)
C(1)—N(2)—C(2)
C(3)—N(1)—C(1)
N(2)—C(1)—S(1)
N(2)—C(2)—C(3)
N(2)—C(1)—N(1) 114.9(2)
N(1)—C(3)—C(2)
C(4)—C(2)—N(2)
105.3(2)
107.5(2)
126.7(2)
109.6(2)
C(10)
N(1)—C(1) 1.392(4)
N(1)—C(3) 1.390(4)
N(2)—C(1) 1.295(3)
N(2)—C(2) 1.397(4)
C(2)—C(3) 1.345(4)
C(3)—C(4) 1.493(4)
O(1)
N(3)
N(1)
S
S(1)
C(8)
C(7)
C(6)
C(5)
C(14)
C(9)
N(2)
C(3)
C(2)
C(1)
N(2)
102.6(2)
129.3(3)
C(4)
C(5)
C(4)
N(1)
C(1)
bond distribution has been observed earlier in analoꢀ
gous N(3)ꢀunsubstituted 5ꢀ(2ꢀpyridylmethylene)thioꢀ
hydantoin18 and 5ꢀ(2ꢀpyridylmethylene)hydantoin18,20
studied by Xꢀray diffraction. In molecule 1a, as in the
Nꢀunsubstituted analogs,18,20 the N(1) and N(2) atoms
are involved in an intramolecular hydrogen bond
(N(1)—H(1), 2.203 Å). Apparently, this hydrogen bond
additionally stabilizes the (Z) configuration of comꢀ
pound 1a.
The overall view of molecule 2a and the atomic numꢀ
bering scheme are presented in Fig. 1, b. The pyridine and
thiohydantoin rings of molecule 2a are in a single plane.
The benzene ring is orthogonal to the plane of the heteroꢀ
cycles. In contrast to thiohydantoin 1a, molecule 2a
adopts the second possible conformation, in which conꢀ
jugation between the pyridine ring and the double bond
persists. In molecule 1a, the N atom of the pyridine ring
forms a hydrogen bond with the NH group of thioꢀ
C(6)
C(7)
N(3)
C(9)
C(2)
C(8)
C(3)
Fig. 1. Molecular structures of compounds 1 (a) and 2 (b) proꢀ
jected onto the plane of the thiohydantoin ring.
hydantoin, whereas the N atom in compound 2a is oriꢀ
ented in the opposite direction. In molecule 2a, there is a
CH...N interaction between the H atom at C(6) and the
N(2) atom, which can be considered as a weak intramoꢀ
lecular hydrogen bond.25
In the crystal structure of compound 1a (Fig. 2), the
molecules are arranged in layers parallel to the crystalloꢀ
graphic plane AC (see Fig. 2, a). In the layers, molecules
1a are linked to each other via intermolecular hydrogen
bonds of three types: S(1)...H(4) (2.992 Å), O(1)...H(1)
a
b
c
Fig. 2. Crystal structure of compound 1a (a); the packing of the molecules in layers and a hydrogen bond network formed by
molecules 1a (b); π—π stacking interactions between the pyridine and thiohydantoin rings (c).

2854
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 12, December, 2004
Majouga et al.
were recorded in CDCl3 on a Varian VXRꢀ400 instrument operꢀ
ating at 400 and 100 MHz, respectively. The IR spectra were
measured on a Perkin—Elmer spectrometer as Nujol mulls.
Xꢀray diffraction study was carried out on a Syntex P21
diffractometer at 153 K (compound 1a) or 293 K (compound 2a)
(graphite monochromator, λ(MoꢀKα) = 0.71073 Å, ω scanning
technique). The absorption corrections were applied based on
the intensities of equivalent reflections (Tmin/Tmax). The strucꢀ
tures were solved by direct methods (SHELXSꢀ9727) and refined
by the fullꢀmatrix leastꢀsquares method against F 2 with anisoꢀ
tropic displacement parameters for all nonhydrogen atoms
(SHELXLꢀ9728). All H atoms were located from difference elecꢀ
tron density maps and refined isotropically. Crystallographic
data and details of the structure solution and refinement of
compounds 1a and 2a are given in Table 2.
a
b
3ꢀPhenylꢀ5ꢀ(pyridylmethylene)ꢀ2ꢀthioxoimidazolinꢀ4ꢀones
(general procedure). A. Pyridinecarboxaldehyde (0.64 g, 6 mmol)
was added dropwise with stirring to a mixture of 3ꢀphenylꢀ2ꢀ
thioxotetrahydroꢀ4Hꢀimidazolꢀ4ꢀone (1.0 g, 5.2 mmol), anꢀ
hydrous sodium acetate (1.16 g, 14.15 mmol), and acetic acid
(7.5 mL). The reaction mixture was refluxed with stirring for 4 h,
cooled to room temperature, and poured onto ice. The precipiꢀ
tate that formed was filtered off and recrystallized from a 3 : 1
EtOH—DMF mixture.
В. Pyridinecarboxaldehyde (0.56 g, 5.2 mmol) was added
dropwise to a solution of 3ꢀphenylꢀ2ꢀthioxotetrahydroꢀ4Hꢀ
imidazolꢀ4ꢀone (1.0 g, 5.2 mmol) in a 2% ethanolic solution of
KOH (14 mL). The reaction mixture was stirred for 12 h. The
precipitate that formed was filtered off and dissolved in water,
after which the solution was neutralized with dilute HCl to pH 7
with vigorous stirring. The precipitate that formed was filtered
off and recrystallized from a 3 : 1 EtOH—DMF mixture.
C. A solution of phenyl isothiocyanate (5.0 g, 37 mmol),
glycine (2.78 g, 37 mmol), and pyridinecarboxaldehyde (4.0 g,
37 mmol) in glacial acetic acid (10 mL) was refluxed for 1 h.
Then the solution was cooled to room temperature. The precipiꢀ
tate that formed was filtered off and recrystallized from a 3 : 1
EtOH—DMF mixture.
3ꢀPhenylꢀ(5Z)ꢀ5ꢀ(pyridinꢀ2ꢀylmethylene)ꢀ2ꢀthioxoimidꢀ
azolinꢀ4ꢀone (1a). M.p. 245 °C (cf. lit. data29: m.p. 243 °C).
1H NMR, δ: 11.95 (br.s, 1 H, NH); 8.79 (d, 1 H, H(6), Py, J =
4.7 Hz); 7.94 (t, 1 H, H(5), Py, J = 8.3 Hz); 7.80 (d, 1 H, H(3),
Py, J = 7.9 Hz); 7.47 (m, 6 H, H(4), Py, Ph); 6.81 (s, 1 H,
=CH). IR, ν/cm–1: 3320 (NH); 1750 (C=O); 1600 (C=C).
3ꢀPhenylꢀ(5Z)ꢀ5ꢀ(pyridinꢀ3ꢀylmethylene)ꢀ2ꢀthioxoimidꢀ
azolinꢀ4ꢀone (1b). M.p. 217 °C. Found (%): C, 63.63; H, 3.72;
N, 14.65. C15H11N3OS. Calculated (%): C, 64.06; H, 3.91;
N, 14.95. 1H NMR, δ: 12.45 (br.s, 1 H, NH); 8.94 (d, 1 H,
H(2), Py, J = 8.8 Hz); 8.51 (d, 1 H, H(6), Py, J = 8.3 Hz); 8.25
(d, 1 H, H(4), Py, J = 8.3 Hz); 7.42 (m, 6 H, H(5), Py, Ph); 6.71
(s, 1 H, =CH). 13C NMR, δ: 179.0, 163.6, 151.2, 149.5, 136.5,
133.1, 128.7, 123.7, 123.1, 114.8, 108.8. IR, ν/cm–1: 3260 (NH);
1730 (C=O); 1600 (C=C).
Fig. 3. Crystal structure of compound 2a and a hydrogen bond
network formed by molecules 2a (a); the packing of the molꢀ
ecules in layers (b).
(2.598 Å), and O(1)...H(2) (2.445 Å). As a result, each
molecule is involved in six hydrogen bonds (see Fig. 2, b).
(Earlier, it has been demonstrated25 that the C—H bonds,
including even those involved in very weakly polarized
Me groups, can participate in hydrogen bonding.) The
nearest molecules of the adjacent layers are arranged in a
headꢀtoꢀtail fashion (see Fig. 2, c). The distance between
the centroids of the pyridine and thiohydantoin rings is
3.667 Å. The distances between the adjacent atoms
(C(1)—C(7) and C(2)—C(9)) are 3.303 and 3.365 Å, reꢀ
spectively, which corresponds27 to a π—πꢀstacking interꢀ
action between the aboveꢀmentioned rings.
In the crystal, molecules 2a are linked to each other
via CH...N hydrogen bonds between the H(13) atom of
one molecule and the N(3) atom of another molecule
(the distance between these atoms is 2.50 Å) to form
zigzag chains (Fig. 3, a). The chains of the molecules are
packed in parallel layers (Fig. 3, b), which are weakly
linked to each other (the distance between the planes of
the pyridine rings of the adjacent layers is 3.61 Å).
3ꢀPhenylꢀ(5Z)ꢀ5ꢀ(pyridinꢀ4ꢀylmethylene)ꢀ2ꢀthioxoimidꢀ
azolinꢀ4ꢀone (1c). M.p. 262 °C (with decomp.). Found (%):
C, 63.72; H, 3.85; N, 14.73. C15H11N3OS. Calculated (%):
C, 64.06; H, 3.91; N, 14.95. 1H NMR, δ: 12.72 (br.s, 1 H, NH);
8.64 (d, 2 H, H(2), H(6), Py, J = 5.3 Hz); 7.71 (d, 2 H, H(3),
H(5), Py, J = 5.3 Hz); 7.42 (m, 5 H, Ph); 6.51 (s, 1 H, =CH).
13C NMR, δ: 179.4, 163.6, 149.9, 139.5, 133.0, 128.8, 128.6,
123.6, 108.6. IR, ν/cm–1: 3260 (NH); 1751 (C=O); 1600 (C=C).
Experimental
Commercial pyridinecarboxaldehydes (Lancaster) were used
in the synthesis without additional purification. 3ꢀPhenylꢀ2ꢀ
thiohydantoin was synthesized according to a procedure deꢀ
scribed earlier.14 The 1H and 13C NMR spectra (DMSOꢀd6)

2ꢀThiohydantoins and their Sꢀmethylation
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 12, December, 2004 2855
2ꢀMethylthioꢀ3ꢀphenylꢀ5ꢀ(pyridylmethylene)ꢀ3,5ꢀdihydroꢀ
4Hꢀimidazolꢀ4ꢀones (2a—c) (general procedure). Water (10 mL),
EtOH (10 mL), and a 15% aqueous KOH solution (2 mL) were
added to the corresponding 3ꢀphenylꢀ5ꢀ(pyridylmethylene)ꢀ2ꢀ
thioxotetrahydroꢀ4Hꢀimidazolꢀ4ꢀone (1a—c) (1.1 g, 4.1 mmol).
After complete dissolution of the precipitate, iodomethane
(1.18 g, 0.54 mL, 8.2 mmol) was added, and the reaction mixꢀ
ture was stirred for 2—3 h. The precipitate that formed was
filtered off and washed on a filter successively with EtOH
and Et2O.
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2ꢀMethylthioꢀ3ꢀphenylꢀ5ꢀ(pyridinꢀ2ꢀylmethylene)ꢀ3,5ꢀdiꢀ
hydroꢀ4Hꢀimidazolꢀ4ꢀone (2a). The yield was 0.8 г (67%),
m.p. 206 °C. Found (%): C, 64.77; H, 4.54; N, 14.25.
C16H13N3OS. Calculated (%): C, 65.08; H, 4.41; N, 14.24.
1H NMR, δ: 8.69 (d, 1 H, H(6), Py, J = 8.3 Hz); 8.53 (d, 1 H,
H(3), Py, J = 4.4 Hz); 8.03 (t, 1 H, H(4), Py, J = 4.4 Hz); 7.46
(m, 6 H, H(5), Py, Ph); 6.88 (s, 1 H, CH=); 2.70 (s, 3 H, Me).
13C NMR, δ: 173.5, 166.7, 165.2, 151.8, 147.9, 138.1, 134.1,
127.5, 127.2, 125.2, 122.1, 121.1, 11.3. IR, ν/cm–1: 1730 (C=O);
1650 (C=N); 1600 (C=C).
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2ꢀMethylthioꢀ3ꢀphenylꢀ5ꢀ(pyridinꢀ3ꢀylmethylene)ꢀ3,5ꢀdiꢀ
hydroꢀ4Hꢀimidazolꢀ4ꢀone (2b). The yield was 0.85 g (71%),
m.p. 167 °C. Found (%): C, 65.22; H, 4.09; N, 14.25; S, 10.63.
C
16H13N3OS. Calculated (%): C, 65.08; H, 4.41; N, 14.24;
S, 10.85. 1H NMR, δ: 9.22 (s, 1 H, H(2), Py); 8.69 (d, 1 H,
H(6), Py, J = 8.3 Hz); 8.53 (d, 1 H, H(4), Py, J = 4.4 Hz); 7.46
(m, 6 H, H(5), Py, Ph); 6.88 (s, 1 H, CH=); 2.70 (s, 3 H, Me).
13C NMR, δ: 166.2, 150.8, 148.1, 137.5, 136.1, 128.2, 127.7,
125.7, 122.0, 117.4, 97.0. IR, ν/cm–1: 1740 (C=O); 1610 (C=C);
1650 (C=N).
2ꢀMethylthioꢀ3ꢀphenylꢀ5ꢀ(pyridinꢀ4ꢀylmethylene)ꢀ3,5ꢀdiꢀ
hydroꢀ4Hꢀimidazolꢀ4ꢀone (2c). The yield was 0.73 g (61%),
m.p. 225 °C. 1H NMR, δ: 8.66 (d, 2 H, H(2), H(6), Py, J =
6.1 Hz); 7.97 (d, 2 H, H(3), H(5), Py, J = 6.1 Hz); 7.46 (m, 5 H,
Ph); 6.83 (s, 1 H, CH=); 2.71 (s, 3 H, Me). 13C NMR, δ: 202.4,
168.6, 150.3, 141.1, 138.5, 132.2, 129.6, 127.2, 125.0, 120.2,
13.2. IR, ν/cm–1: 1745 (C=O); 1600 (C=C); 1650 (C=N).
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This study was financially supported by the Russian
Foundation for Basic Research (Project No. 03ꢀ03ꢀ
32401), the Research Program "Russian Universities"
(Grant 05.03.046), and the Presidium of the Russian
Academy of Sciences (Program "Theoretical and Experiꢀ
mental Studies of the Nature of Chemical Bonding and
Mechanisms of Chemical Reactions and Processes").
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Trans. 2, 1986, 1941.
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Crystal Structures. University of Göttingen, Göttingen, Gerꢀ
many, 1997.
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Received May 12, 2004;
in revised form September 9, 2004