A novel synthesis of thioglycolurils by ring contraction of 5,7-dialkyl-3-thioxoperhydroimidazo[4,5- e ]-1,2,4-triazin-6-ones

Article abstract of DOI:10.1055/s-0032-1317194

A new synthetic route to (E)-1,3-dialkyl-4-(benzylideneamino)-5- thioxohexahydroimidazo[4,5-d]imidazol-2(1H)-ones (thioglycolurils), by a ring contraction reaction of 5,7-dialkyl-3-thioxoperhydroimidazo[4,5-e]-1,2,4- triazin-6-ones with aromatic aldehydes, has been developed.

Full text of DOI:10.1055/s-0032-1317194

3366▌
PAPER
paper
A Novel Synthesis of Thioglycolurils by Ring Contraction of
5,7-Dialkyl-3-thioxoperhydroimidazo[4,5-e]-1,2,4-triazin-6-ones
Novel Synthesis of Thioglycolurils
Galina A. Gazieva,*a Pavel A. Poluboyarov,a Leonid D. Popov,b Natalya G. Kolotyrkina,a Angelina N. Kravchenko,a
Nina N. Makhovaa
a
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky prosp., 119991 Moscow, Russian Federation
Fax +7(499)1355328; E-mail: gaz@ioc.ac.ru
b
Department of Chemistry, Southern Federal University, 7 Zorge Street, 344090 Rostov-on-Don, Russian Federation
Received: 24.05.2012; Accepted after revision: 16.08.2012
can be readily prepared by isolation of dihydroxyimid-
Abstract: A new synthetic route to (E)-1,3-dialkyl-4-(benzylid-
azolidine-2-one I, followed by treatment with different
eneamino)-5-thioxohexahydroimidazo[4,5-d]imidazol-2(1H)-ones
ureas.2,3,6,8 Yields of glycolurils II are in general respect-
(thioglycolurils), by a ring contraction reaction of 5,7-dialkyl-3-
thioxoperhydroimidazo[4,5-e]-1,2,4-triazin-6-ones with aromatic
aldehydes, has been developed.
able, and a wide range of these compounds has been syn-
thesized by this procedure.2,3,6,7a,b,d
Key words: N-heterocycles, thioglycolurils, 3-thioxoperhydro-
imidazo[4,5-e]-1,2,4-triazin-6-ones, aromatic aldehydes, ring con-
traction
R1
R2
O
O
NH
+
O
R2
NH
R1
Glycolurils [tetrahydroimidazo[4,5-d]imidazole-2,5(1H,3H)-
diones] possess a broad spectrum of biological activities.
The best known is mebicar, or adaptol [1,3,4,6-tetra-
methyltetrahydroimidazo[4,5-d]imidazole-2,5(1H,3H)-dione],
which was introduced into medical practice in 1979 and
has been successfully used as a day-time tranquilizer in
Russia.1 A pharmacological study of N-(carboxyal-
kyl)glycolurils revealed their anxiolytic and sedative
effects.2 1-(2-Acetylaminoethyl)-3-methylglycoluril ex-
hibited nootropic activity.3 In addition, some 3a,6a-diphe-
nylglycolurils are known to affect the cytochrome P-450-
dependent monooxygenase system of liver.4 Thioana-
logues of glycolurils have more potential bioactivity than
glycolurils according to the data of PASS (Prediction of
Activity Spectra for Substances) method.5
R1
NH
O
R1
R1
R1
R2
R2
NH
R1
OH
OH
N
N
N
O
O
O
N
R1
N
N
R1
R2
R1
R2
I
II
Scheme 1 Synthesis of glycolurils
In contrast, condensations of thioureas with α-dicarbonyl
compounds often fail to generate corresponding dithio-
glycolurils. A variety of alternative products have been
formed in these reactions, namely thiohydantoins,9 4,5-di-
hydroxyimidazolidine-2-thiones, imidazoline-2-thiones,
or disulfides derived therefrom.10 A reaction of 4,5-dihy-
droxyimidazolidine-2-thiones with ureas generates mono-
thioglycolurils in respectable yields;10,11 however,
thioureas give variable results under the same conditions:
some fail to react.7d,11 Similar results were obtained when
a reaction of 4,5-dihydroxyimidazolidine-2-one I with
thioureas was performed. High yields of thioglycolurils
were obtained only for 3a,6a-diphenylthioglycolurils.12
Therefore, alternative routes to thioglycolurils need to be
explored.
Over the last years we have developed synthetic methods
and studied the biological activity of glycolurils.2,3,6 Our
interest in the synthesis of heterocyclic compounds of bi-
ological importance encouraged us to study the prepara-
tion of thioanalogues of glycolurils. However, in seeking
a route to prepare thioanalogues of glycolurils it became
apparent that these compounds had been relatively little
explored.
Condensation reactions of ureas with α-dicarbonyl com-
pounds such as glyoxal, benzyl, or diacetyl have been ex-
tensively studied and generally proceed readily: initial
cyclization produces monocyclic 4,5-dihydroxyimid-
azolidine-2-one I that may be isolated under neutral or al-
kaline conditions.7 Then this intermediate reacts with
another mole of urea to give corresponding glycoluril II
(Scheme 1).6a,7a–d Asymmetrically substituted glycolurils
Thioglycolurils were prepared by the addition of isothio-
cyanatotrimethylsilane to 1,4-diaza-1,3-dienes;13 howev-
er, this method is of limited utility. Cow and Harrison
described a simple method for the conversion of glycol-
urils to corresponding mono- or dithio derivatives using
Lawesson’s reagent [2,4-bis(4-methoxyphenyl)-1,3-di-
thia-2,4-diphosphetane-2,4-disulfide].14 Recently,15 we
have found that the cyclization of 1,3-dialkyl-4,5-
bis(thiosemicarbazido)imidazolidin-2-ones 1 with benz-
aldehydes 2 in methanol in the presence of HCl leads to
SYNTHESIS 2012, 44, 3366–3370
Advanced online publication: 05.09.2012
0
0
3
9
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7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0032-1317194; Art ID: SS-2012-N0465-OP
© Georg Thieme Verlag Stuttgart · New York

PAPER
Novel Synthesis of Thioglycolurils
3367
thiosemicarbazones of aldehydes 3, and to the hitherto cyclization step that results in the perhydro-1,2,4-triazine
unknown
(E)-1,3-dialkyl-4-(benzylideneamino)-5-thi- ring contraction to the imidazolidine ring (Scheme 4).15
oxohexahydroimidazo[4,5-d]imidazol-2(1H)-ones 4 (thio-
glycolurils of a new substitution type). In addition to
compounds 3 and 4, 5,7-dialkyl-3-thioxoperhydroimid-
azo[4,5-e]-1,2,4-triazin-6-ones 5 were generated in a
small amount when less than 2 moles of aldehyde 2 per 1
mole of starting imidazolidinone 1 were used (Scheme 2).
R4
R5
R3
R2
O
H
H+
R1
R1
H
H
N
MeOH, HCl
reflux, 1 h
R2
R3
HO
N
N
NH
N
+
NH
O
O
S
H
O
N
R1
R5
S
R1
N
N
H
N
R1
H
N
N
H
S
MeOH, HCl
reflux
R4
2a–f
N
H
NH2
NH2
O
5a,b
+
H
N
N
R1
N
H
– H2O
R2
S
1
2
R4
R2
R4
R3
R5
R3
R2
H
R2
R5
S
NNHCNH2
H
R1
R1
N
N
N
R1
N
R1
N
N
H
N
H
N
H
H
N
N
N
NH
O
O
S
O
+
+
O
S
– H+
N
R1
N
R1
N
H
N
R1
N
H
S
N
R1
N
H
N
S
H
R2
3
4 20–58%
5
4a–l
R1 = Me, Et; R2 = H, Br
Scheme 4 Reaction of 3-thioxoperhydroimidazo[4,5-e]-1,2,4-tri-
azin-6-ones 5a,b with aromatic aldehydes 2a–f
Scheme 2 Cyclization of 4,5-bis(thiosemicarbazido)imidazolidin-2-
ones with benzaldehydes
Table 1 Thioglycolurils 4a–l Prepared
Boiling hexahydro-1,2,4-triazine-3,6-dione with benzal-
dehyde in acetic acid was reported to led to 1-(benzylid-
eneamino)imidazolidin-2-one in 17% yield.16 We
envisaged that imidazotriazines 5 could be intermediates
for the formation of thioglycolurils 4 and are capable of
reacting with aromatic aldehydes.
Product
R1
R2
R3
R4
R5
Yield (%)
4a
4b
4c
4d
4e
4f
Me
Me
Me
Me
Me
Me
Me
Et
H
H
H
H
OMe
H
H
I
H
H
F
H
H
H
H
Cl
Br
I
55
56
58
60
51
53
39
59
64
59
51
49
OH
H
Starting materials, imidazo[4,5-e]-1,2,4-triazin-6-ones
5a,b, were prepared by cyclization of 4,5-dihydroxyimid-
azolidin-2-ones 6a,b with thiosemicarbazide (Scheme
3).17
OH
OH
OH
OH
H
H
H
H
H
H
H
H
H
H
4g
4h
4i
R1
N
R1
N
H
N
MeOH, HCl
reflux
OH
H2N
H2N
H
H
H
H
I
H
H
Cl
Br
I
NH
NH
+
O
O
Et
OH
OH
OH
OH
N
R1
N
R1
S
N
H
S
OH
4j
Et
6a,b
5a,b 90–96%
4k
4l
Et
R1 = Me (a), Et (b)
Et
Scheme 3 Preparation of 3-thioxoperhydroimidazo[4,5-e]-1,2,4-tri-
azin-6-ones
Reaction temperature, solvent (methanol, ethanol, pro-
pan-2-ol, acetic acid) and reaction time effects were stud-
ied. The best yields of thioglycolurils were achieved in
methanol in the presence of HCl under reflux (Table 1).
We describe here a novel reaction for the synthesis of
(E)-1,3-dialkyl-4-(benzylideneamino)-5-thioxohexahydro-
imidazo[4,5-d]imidazole-2(1H)-ones 4 [1,3-dialkyl-4-
(benzylideneamino)thioglycolurils]. Novel thioglycol-
urils 4a–l (Table 1) were synthesized by reacting 3-
thioxoperhydroimidazo[4,5-e]-1,2,4-triazin-6-ones 5a,b
with aromatic aldehydes 2a–f. The reaction includes a re-
Compounds 4a–l were fully characterized on the basis of
the IR, 1H NMR, 13C NMR, and HRMS spectral data, and
X-ray analysis for 4a,b (Figures 1 and 2). These com-
pounds possess the E-configuration.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 3366–3370

3368
G. A. Gazieva et al.
PAPER
done with Electrospray Calibrant Solution (Fluka). A syringe injec-
tion was used for solutions in MeCN or MeOH (flow rate 3
μL/min). N2 was applied as a dry gas; interface temperature was set
at 180 °C.
Thioglycolurils 4a–l; General Procedure
To a stirred suspension of 5,7-dialkyl-3-thioxoperhydroimid-
azo[4,5-e]-1,2,4-triazin-6-one 5a,b (2 mmol) in MeOH (25 mL)
were added concd HCl (1 drop) and the corresponding aromatic al-
dehyde 2a–f (2.2 mmol). The resulting mixture was refluxed with
stirring for 1–1.5 h. After cooling for 4–48 h, the solid product was
filtered and dried. Recrystallization from EtOH gave thioglycoluril
4a–l.
(E)-4-(Benzylideneamino)-1,3-dimethyl-5-thioxohexahydro-
imidazo[4,5-d]imidazol-2(1H)-one (4a)
Yield: 320 mg (55%); white solid; mp 239–241 °C (dec.) [Lit.15 mp
239–241 °C (dec.)].
Figure 1 General view of (E)-4-(benzylideneamino)-1,3-dimethyl-
5-thioxohexahydroimidazo[4,5-d]imidazol-2(1H)-one (4a) in repre-
sentation of atoms via thermal ellipsoids (p = 50%)18
1H NMR and 13C NMR spectral data are consistent with the litera-
ture values.15
(E)-4-[(2-Hydroxybenzylidene)amino]-1,3-dimethyl-5-thioxo-
hexahydroimidazo[4,5-d]imidazol-2(1H)-one (4b)
Yield: 340 mg (56%); white solid; mp 218–220 °C (dec.).
IR (KBr): 3401, 3169, 2951, 1703, 1619, 1574, 1516, 1489, 1426,
1267, 1215, 1036, 811, 762 cm–1.
1H NMR (300.13 MHz, DMSO-d6): δ = 2.78 (s, 3 H), 2.93 (s, 3 H),
5.49 (d, J = 8.1 Hz, 1 H), 6.17 (d, J = 8.1 Hz, 1 H), 6.92–6.97 (m, 2
H), 7.33 (t, J = 7.6 Hz, 1 H), 7.58 (d, J = 7.6 Hz, 1 H), 8.82 (s, 1 H),
10.29 (s, 1 H), 11.11 (s, 1 H).
13C NMR (75.5 MHz, DMSO-d6): δ = 179.7, 157.6, 157.3, 147.7,
131.7, 130.1, 119.4, 118.4, 116.7, 72.3, 68.9, 30.9, 28.3.
HRMS (ESI): m/z [M + H]+ calcd for C13H15N5O2S: 306.1019;
found: 306.1025.
(E)-4-[(4-Fluorobenzylidene)amino]-1,3-dimethyl-5-thioxo-
hexahydroimidazo[4,5-d]imidazol-2(1H)-one (4c)
Yield: 360 mg (58%); white solid; mp 234–236 °C (dec.).
Figure 2 General view of (E)-4-[(2-hydroxybenzylidene)amino]-
1,3-dimethyl-5-thioxohexahydroimidazo[4,5-d]imidazol-2(1H)-one
(4b) in representation of atoms via thermal ellipsoids (p = 50%)18
IR (KBr): 3262, 2934, 1702, 1690, 1599, 1505, 1488, 1406, 1270,
1230, 1205, 1152, 1056, 840, 792 cm–1.
1H NMR (300.13 MHz, DMSO-d6): δ = 2.75 (s, 3 H), 2.85 (s, 3 H),
5.40 (d, J = 8.3 Hz, 1 H), 5.95 (d, J = 8.3 Hz, 1 H), 7.32 (t, J = 8.7
Hz, 2 H), 7.82 (dd, J = 8.2, 5.9 Hz, 2 H), 9.09 (s, 1 H), 10.03 (s, 1 H).
13C NMR (75.5 MHz, DMSO-d6): δ = 179.0, 163.5 (d, J = 248 Hz),
157.5, 150.4, 130.5 (d, J = 2.9 Hz), 129.6 (d, J = 8.8 Hz), 116.0 (d,
J = 22 Hz), 74.9, 68.1, 30.1, 28.2.
It is worth noting that the synthesized compounds 4 are
also cyclic derivatives of thiosemicarbazones. Thiosemi-
carbazones, including their cyclic derivatives, exhibit an-
tiviral, antibacterial, antifungal, anticancer, and other
activities.19
HRMS (ESI): m/z [M + H]+ calcd for C13H14FN5OS: 308.0976;
found: 308.0978.
In summary, we have discovered a new reaction type that
leads to the formation of substituted thioglycolurils con-
taining differently substituted benzylideneamino frag-
ments. Novel (E)-1,3-dialkyl-4-(benzylideneamino)-5-thi-
oxohexahydroimidazo[4,5-d]imidazol-2(1H)-ones [1,3-
(E)-4-[(2-Hydroxy-3-methoxybenzylidene)amino]-1,3-dimeth-
yl-5-thioxohexahydroimidazo[4,5-d]imidazol-2(1H)-one (4d)
Yield: 400 mg (60%); white solid; mp 221–223 °C (dec.).
IR (KBr): 3235, 2996, 2957, 1719, 1612, 1576, 1516, 1488, 1417,
dialkyl-4-(benzylideneamino)thioglycolurils] were syn- 1257, 1201, 1035, 780 cm–1.
1H NMR (300.13 MHz, DMSO-d6): δ = 2.77 (s, 3 H), 2.92 (s, 3 H),
3.80 (s, 3 H), 5.49 (d, J = 8.1 Hz, 1 H), 6.17 (d, J = 8.1 Hz, 1 H),
6.88 (t, J = 7.8 Hz, 1 H), 7.05 (d, J = 7.8 Hz, 1 H), 7.17 (d, J = 7.8
Hz, 1 H), 8.84 (s, 1 H), 10.27 (s, 1 H), 10.92 (s, 1 H).
thesized by the reaction of 5,7-dialkyl-3-thioxoperhydro-
imidazo[4,5-e]-1,2,4-triazin-6-ones with aromatic al-
dehydes.
13C NMR (75.5 MHz, DMSO-d6): δ = 179.5, 157.5, 148.1, 147.6,
147.1, 121.4, 119.0, 118.5, 114.2, 72.3, 68.8, 55.9, 30.8, 28.2.
HRMS (ESI): m/z [M + H]+ calcd for C14H17N5O3S: 336.1125;
found: 336.1127.
1H NMR and 13C NMR spectra were recorded on a Bruker AM300
spectrometer operating at 300.13 MHz and 75.5 MHz, respectively,
using DMSO-d6 as solvent. Chemical shifts (δ) are given in ppm
from TMS as internal standard. High-resolution mass spectra
(HRMS) were measured on the Bruker micrOTOF II instrument us-
ing electrospray ionization (ESI). The measurements were done in
a positive ion mode (interface capillary voltage: 4500 V); mass
range from m/z 50 to 3000 Da; external or internal calibration was
(E)-4-[(5-Chloro-2-hydroxybenzylidene)amino]-1,3-dimethyl-
5-thioxohexahydroimidazo[4,5-d]imidazol-2(1H)-one (4e)
Yield: 350 mg (51%); white solid; mp 225–227 °C (dec.).
Synthesis 2012, 44, 3366–3370
© Georg Thieme Verlag Stuttgart · New York

PAPER
Novel Synthesis of Thioglycolurils
3369
IR (KBr): 3432, 3160, 2991, 2933, 1729, 1614, 1570, 1523, 1479,
1444, 1415, 1274, 1211, 1041, 923, 745 cm–1.
IR (KBr): 3437, 3215, 2980, 2971, 2935, 1703, 1692, 1615, 1568,
1507, 1478, 1439, 1270, 1252, 1203, 1070, 913, 799 cm–1.
1H NMR (300.13 MHz, DMSO-d6): δ = 2.78 (s, 3 H), 2.94 (s, 3 H),
5.49 (d, J = 8.3 Hz, 1 H), 6.13 (d, J = 8.3 Hz, 1 H), 6.96 (d, J = 8.8
Hz, 1 H), 7.34 (dd, J = 8.8, 2.5 Hz, 1 H), 7.68 (d, J = 2.5 Hz, 1 H),
8.80 (s, 1 H), 10.36 (s, 1 H), 11.20 (s, 1 H).
13C NMR (75.5 MHz, DMSO-d6): δ = 179.6, 157.5, 155.8, 144.8,
130.9, 128.5, 122.9, 120.1, 118.5, 72.3, 68.9, 30.9, 28.2.
1H NMR (300.13 MHz, DMSO-d6): δ = 1.02 (d, J = 7.1 Hz, 3 H),
1.09 (d, J = 7.1 Hz, 3 H), 3.10–3.48 (m, 4 H), 5.58 (d, J = 8.3 Hz, 1
H), 6.13 (d, J = 8.3 Hz, 1 H), 6.96 (d, J = 8.8 Hz, 1 H), 7.34 (dd,
J = 8.8, 2.5 Hz, 1 H), 7.67 (d, J = 2.5 Hz, 1 H), 8.92 (s, 1 H), 10.26
(s, 1 H), 11.01 (s, 1 H).
13C NMR (75.5 MHz, DMSO-d6): δ = 179.3, 156.9, 155.9, 146.2,
131.2, 127.6, 123.0, 120.3, 118.5, 72.1, 66.9, 37.8, 35.9, 13.7, 12.9.
HRMS (ESI): m/z [M + H]+ calcd for C15H18ClN5O2S: 368.0942;
HRMS (ESI): m/z [M + H]+ calcd for C13H14ClN5O2S: 340.0629;
found: 340.0617.
found: 368.0933.
(E)-4-[(5-Bromo-2-hydroxybenzylidene)amino]-1,3-dimethyl-
5-thioxohexahydroimidazo[4,5-d]imidazol-2(1H)-one (4f)
Yield: 410 mg (53%); white solid; mp 231–233 °C (dec.).
(E)-4-[(5-Bromo-2-hydroxybenzylidene)amino]-1,3-diethyl-5-
thioxohexahydroimidazo[4,5-d]imidazol-2(1H)-one (4k)
Yield: 420 mg (51%); white solid; mp 204–206 °C (dec.).
IR (KBr): 3422, 3171, 2959, 2924, 1721, 1614, 1563, 1529, 1492,
1476, 1411, 1268, 1205, 1042, 804, 742 cm–1.
1H NMR (300.13 MHz, DMSO-d6): δ = 2.77 (s, 3 H), 2.94 (s, 3 H),
5.48 (d, J = 8.2 Hz, 1 H), 6.11 (d, J = 8.2 Hz, 1 H), 6.90 (d, J = 8.7
Hz, 1 H), 7.44 (d, J = 8.7 Hz, 1 H), 7.80 (s, 1 H), 8.77 (s, 1 H), 10.36
(s, 1 H), 11.22 (s, 1 H).
13C NMR (75.5 MHz, DMSO-d6): δ = 179.6, 157.5, 156.2, 144.7,
133.7, 131.4, 120.7, 118.9, 110.3, 72.3, 68.9, 30.9, 28.2.
HRMS (ESI): m/z [M + H]+ calcd for C13H14BrN5O2S: 384.0124;
found: 384.0115.
IR (KBr): 3441, 3217, 2979, 2969, 2933, 1702, 1693, 1613, 1564,
1507, 1475, 1437, 1270, 1252, 1202, 1070, 912, 799 cm–1.
1H NMR (300.13 MHz, DMSO-d6): δ = 1.01 (d, J = 7.0 Hz, 3 H),
1.09 (d, J = 7.1 Hz, 3 H), 3.09–3.49 (m, 4 H), 5.58 (d, J = 8.3 Hz, 1
H), 6.13 (d, J = 8.3 Hz, 1 H), 6.93 (d, J = 8.8 Hz, 1 H), 7.46 (dd,
J = 8.8, 2.2 Hz, 1 H), 7.80 (d, J = 2.2 Hz, 1 H), 8.90 (s, 1 H), 10.25
(s, 1 H), 11.03 (s, 1 H).
13C NMR (75.5 MHz, DMSO-d6): δ = 179.2, 156.8, 156.3, 146.1,
134.0, 130.6, 120.9, 118.9, 110.4, 72.1, 66.9, 37.8, 35.9, 13.7, 12.9.
HRMS (ESI): m/z [M + H]+ calcd for C15H18BrN5O2S: 412.0437;
found: 412.0430.
(E)-4-[(2-Hydroxy-3,5-diiodobenzylidene)amino]-1,3-dimethyl-
5-thioxohexahydroimidazo[4,5-d]imidazol-2(1H)-one (4g)
Yield: 430 mg (39%); yellowish solid; mp 230–232 °C (dec.).
(E)-1,3-Diethyl-4-[(2-hydroxy-3,5-diiodobenzylidene)amino]-5-
thioxohexahydroimidazo[4,5-d]imidazol-2(1H)-one (4l)
Yield: 570 mg (49%); yellowish solid; mp 222–224 °C (dec.).
IR (KBr): 3424, 2921, 1721, 1612, 1544, 1496, 1439, 1399, 1274,
1217, 1206, 1040, 786, 749 cm–1.
IR (KBr): 3385, 2973, 2951, 2931, 1698, 1620, 1591, 1479, 1444,
1245, 1220, 1209, 1064, 914, 796 cm–1.
1H NMR (300.13 MHz, DMSO-d6): δ = 0.97 (d, J = 7.0 Hz, 3 H),
1.10 (d, J = 7.1 Hz, 3 H), 3.12–3.21 (m, 1 H), 3.27–3.50 (m, 3 H),
5.64 (d, J = 8.2 Hz, 1 H), 6.19 (d, J = 8.2 Hz, 1 H), 7.95 (s, 1 H),
8.07 (s, 1 H), 8.45 (s, 1 H), 10.51 (s, 1 H), 12.30 (s, 1 H).
1H NMR (300.13 MHz, DMSO-d6): δ = 2.78 (s, 3 H), 2.95 (s, 3 H),
5.53 (d, J = 8.1 Hz, 1 H), 6.16 (d, J = 8.1 Hz, 1 H), 7.95 (s, 1 H),
8.05 (s, 1 H), 8.49 (s, 1 H), 10.54 (s, 1 H), 12.38 (s, 1 H).
13C NMR (75.5 MHz, DMSO-d6): δ = 179.9, 157.4, 155.8, 146.5,
143.3, 139.1, 120.2, 87.8, 82.0, 71.2, 69.3, 31.0, 28.2.
HRMS (ESI): m/z [M + H]+ calcd for C13H13I2N5O2S: 557.8952;
found: 557.8942.
13C NMR (75.5 MHz, DMSO-d6): δ = 179.7, 156.8, 155.9, 146.7,
144.3, 139.0, 120.1, 88.0, 82.1, 70.5, 67.5, 38.2, 36.0, 14.0, 12.9.
HRMS (ESI): m/z [M + H]+ calcd for C15H17I2N5O2S: 585.9265;
found: 585.9254.
(E)-4-(Benzylideneamino)-1,3-diethyl-5-thioxohexahydroimid-
azo[4,5-d]imidazol-2(1H)-one (4h)
Yield: 370 mg (59%); white solid; mp 226–228 °C (dec.) [Lit.15 mp
226–228 °C (dec.)].
1H NMR and 13C NMR spectral data are consistent with the litera-
Acknowledgment
ture values.15
This work was financially supported by Russian Academy of Sci-
ences [Program ‘Medicinal and Biomolecular Chemistry’ (ChD-9)
of the Division of Chemistry and Materials Science]. The authors
thank Dr. Yu. V. Nelyubina (A. N. Nesmeyanov Institute of Orga-
noelement Compounds) for X-ray analysis.
(E)-1,3-Diethyl-4-[(2-hydroxybenzylidene)amino]-5-thioxo-
hexahydroimidazo[4,5-d]imidazol-2(1H)-one (4i)
Yield: 430 mg (64%); white solid; mp 220–222 °C (dec.).
IR (KBr): 3401, 3190, 2972, 2931, 1695, 1616, 1573, 1512, 1481,
1461, 1253, 1205, 1061, 807, 744 cm–1.
1H NMR (300.13 MHz, DMSO-d6): δ = 1.02 (d, J = 7.0 Hz, 3 H),
1.09 (d, J = 7.0 Hz, 3 H), 3.10–3.47 (m, 4 H), 5.58 (d, J = 8.3 Hz, 1
H), 6.18 (d, J = 8.3 Hz, 1 H), 6.92–6.95 (m, 2 H), 7.33 (t, J = 7.6 Hz,
1 H), 7.59 (d, J = 7.5 Hz, 1 H), 8.91 (s, 1 H), 10.20 (s, 1 H), 10.91
(s, 1 H).
13C NMR (75.5 MHz, DMSO-d6): δ = 179.3, 157.3, 156.9, 149.3,
131.9, 129.4, 119.4, 118.4, 116.6, 72.0, 66.9, 37.8, 35.9, 13.7, 12.9.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnoIufproi
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tgioSrantnugIifoop
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References
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© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 3366–3370

3370
G. A. Gazieva et al.
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© Georg Thieme Verlag Stuttgart · New York