Eco-friendly synthesis of novel thiohydantoin-type sulfur-containing imidazolinone derivatives from glycine ester

Article abstract of DOI:10.1007/s10593-018-2247-5

[Figure not available: see fulltext.] Imino derivatives of glycine ester were prepared from methyl glycinate by the known procedure and then they reacted with several amines under microwave irradiation without solvent that gave the corresponding glycine a

Full text of DOI:10.1007/s10593-018-2247-5

DOI 10.1007/s10593-018-2247-5
Chemistry of Heterocyclic Compounds 2018, 54(2), 153–157
This work is dedicated to the memory of Professor Yiannis Elemes
Eco-friendly synthesis of novel thiohydantoin-type
sulfur-containing imidazolinone derivatives from glycine ester
Mustafa Kemal Gümüş1,2*, Yiannis Elemes2†
1 Science-Technology Research and Application Center, Artvin Coruh University,
Artvin 08000, Turkey; e-mail: mkgumus@artvin.edu.tr
2 Department of Chemistry, University of Ioannina,
Ioannina 45110, Greece
Published in Khimiya Geterotsiklicheskikh Soedinenii,
2018, 54(2), 153–157
Submitted September 27, 2017
Accepted February 2, 2018
Imino derivatives of glycine ester were prepared from methyl glycinate by the known procedure and then they reacted with several
amines under microwave irradiation without solvent that gave the corresponding glycine amides. By the one-component cyclocondensa-
tion, the obtained amide derivatives were transformed into thiohydantoin-type imidazolinones using solvent-free microwave procedure.
All imine-ester derivatives and most of the imidazolinone derivatives were synthesized for the first time. This eco-friendly protocol can
provide a suitable way for synthesizing new potentially bioactive imidazolinone derivatives.
Keywords: glycine ester, imidazolinone thiohydantoin, imidazolone, microwave irradiation, solvent-free synthesis.
One important aspect of benign chemical technologies is
to remove organic solvents in chemical synthesis due to
their toxicity and difficulties in containing volatile
compounds. Heterocyclic synthesis methods under solvent-
free conditions have developed rapidly in the past years,1
and the number of reports on rapid, selective, and efficient
transformations with a high degree of conversion of
reactants to products grows every day.2,3
A new green method in organic synthesis is microwave
(MW) radiation, which is widely used as a source of
heating, as it provides spectacular accelerations, higher
yields under milder reaction conditions, and higher product
purities, and it reduces pollution of the environment
through the use of solvent-free reaction protocols.4–6
Solvent-free reaction conditions may provide a wide range
of advantages such as improved atom utilization7 by
avoidance of common derivation procedures;8 decreased
by-product formation and, hence, decreased waste resulting
from purification procedures required to separate the
desired product from the impurities; and, in many
instances, reduced energy utilization both in the reaction
and purification stages, as well as opportunities for process
intensification. Therefore, they can be used as means of
waste reduction and increasing energy efficiency, which is
a critical issue in the field of green chemistry and in the
broader context of public health, the environment
protection, and use renewable resources.2,3
In the past thirty years imidazolone derivatives of
hydantoin (1a) or thiohydantoin (1b) (Fig. 1) have been the
focus of interest for the synthetic and pharmaceutical
industry due to their biological properties, including anti-
convulsant,9 antidepressant,10 anti-inflammatory,11 antiviral12
(including antiHIV13), and antitumor14 activities. Another
important feature is that they are also effective precursors
for the slow release of bioactive volatile compounds15 and
some derivatives have been used with success in crop
protection. Imidazolinone herbicides, for example,
imazapyr (2) (Fig. 1), imazapic, imazethapyr, imazamox,
imazamethabenz, and imazaquin are distinguished selective
herbicides that act by inhibiting the acetohydroxyacid
synthase (AHAS), also known as acetolactate synthase
(ALS), which is a critical enzyme for the biosynthesis of
branched-chain amino acids in plants.16 Some imidazo-
linones also have been found to possess fungicidal
activities, for example, 5-methyl-2-(methylsulfanyl)-5-phenyl-
3-(N-phenylamino)-3,5-dihydroimidazolin-4-one (3), called
fenamidone, shows high fungicidal activities.17
The most common synthetic approach to obtain
imidazolinone skeleton requires the condensation of
α-amino amides with ketones or aldehydes.18–20 Although
such procedures do exist, novel methods for imidazole
synthesis are still in demand. In this regard, Pospíšil and
Potáček21 reported the synthesis of a new series of sub-
stituted imidazolidin-4-ones by the reaction of equimolar
amounts of N-substituted α-amino amides and aldehydes
under solvent-free conditions, using both conventional
† Deceased.
0009-3122/18/54(2)-0153©2018 Springer Science+Business Media, LLC
153

Chemistry of Heterocyclic Compounds 2018, 54(2), 153–157
Scheme 1
O
O
R1X
H
N
CS2, Et3N
–S
H2N
OMe
O
OMe
CHCl3
· HCl
S
6
X = Br, I
R1X
O
H
N
K2CO3
R1S
R1S
N
OMe
OMe
8a–d
Me2CO
S
SR1
7a–d
SR1
R2
O
R2NH2
N
R1S
N
R2
N
H
N
MW, 100°C
30 min
solvent-free
MW
SR1
150°C, 1 h
9a–h
O
solvent-free
10a–h
Figure 1. Structures of some hydantoin-type imidazolinones.
Table 1. Yields of iminoamide derivatives 9a–h
and sulfur-containing imidazolinone derivatives 10a–h
R1
R2
Amide
Yield, %
Imidazolinone
Yield, %
thermal heating and microwave irradiation. A similar
method involves the conversion of an amino acid to a
Schiff base of an N-alkylamino acid amide, followed by
cyclization with benzoic anhydride to give an
N-benzoylimidazolidin-4-one.22
One of the recent methods was presented by Erden et al.
for a one-step synthesis of imidazolidin-4-ones based on
tandem nucleophilic additions–decarboxylation–intramole-
Me
Et
Bn
Bn
Bn
Bn
Bu
Bu
Bu
Bu
88
89
82
85
91
87
85
88
78
77
74
75
77
74
73
70
9a
9b
9c
9d
9e
9f
10a
10b
10c
10d
10e
10f
Pr
Bu
Me
Et
Pr
9g
9h
10g
10h
cular cyclizations of Schiff base with
a Leuchs'
anhydride.23 Some imidazolinone derivatives, such as
2-(alkylsulfanyl)-4H-imidazolin-4-ones 4, have been
synthesized by the aza-Wittig reaction of iminophospho-
ranes to evaluate their biological activities, and some of
them exhibit herbicidal and fungicidal activities.24
Bu
the current study, our aim was to find a new reaction
pathway for these imino ester derivatives and to explore the
possibility of introducing imino ester derivatives in solvent-
free microwave-assisted reaction with several amines
which resulted in imino amide derivatives 9a–h and lastly
to elucidate the scope and limitations of this one-compo-
nent cyclocondensation with formation of imidazolin-
4-ones 10a–h (Scheme 1, Table 1).
More recently, Ramli et al. published one example of
formation of heterocyclic system
5
starting from
thiohydantoin derivative stirred at room temperature in
DMF in the presence of catalytic amount of tetrabutyl-
ammonium bromide.25 Talab et al. obtained 3-benzyl-
2-(methylsulfanyl)imidazolin-4-one (10a) as an inter-
mediate product in a few steps starting from thiocyanate
and glycine amide.26 The imidazolinone ring was used as
building block to obtain 2'-13C-L-histidine in high optical
purity and with high 13C incorporation.
In our new method, methyl N-[bis(alkylsulfanyl)-
methylidene]glycinates 8a–d were prepared from methyl
glycinate (6) by a known procedure27 via dithiocarbamates
7a–d. Esters 8a–d reacted with several amines under
microwave irradiation without solvent that gave glycine
amides 9a–h. Then by the one-component cycloconden-
sation, amides 9a–h were transformed into cyclic
imidazolin-4-ones 10a–h using solvent-free microwave
irradiation as well (Scheme 1, Table 1).
As shown in our previous study,33 a reaction of imino
esters 8a–d with amine derivatives in THF by conventional
heating resulted in the imino amide-type compounds. The
best yields (64–93%) were obtained at 120°C in 4 h.33 In
continuation of our efforts to develop a more effective and
rapid method for the synthesis of imino amide derivatives
9a–h an alternative protocol was elaborated including
microwave heating at 100°C in 30 min, thus increasing
yields to 82–91%. In addition, we developed
a
cyclocondensation reaction to produce, for the first time,
imidazolin-4-ones 10a–h from imino amides 9a–h, which
is environmentally friendly, rapid, and highly efficient
(Scheme 1, Table 1). The yields of the cyclocondensation
reaction were reduced due to the presence of longer
alkylsulfanyl groups on the imino amide.
Previously Elemes et al. have investigated the synthesis,
the biological and chemical properties of pyrrolidine and
pyrroline derivatives formed by 1,3-dipolar cycloaddition
reactions of N-phenylmaleimides28–30 and carbon fulle-
renes31,32 with esterified iminoglycine derivatives 8a–d. In
The structures of new compounds were confirmed by 1H
and 13C NMR spectroscopy, mass spectrometry, and
elemental analyses. Spectroscopic data of the newly
154

Chemistry of Heterocyclic Compounds 2018, 54(2), 153–157
1
synthesized compounds are in accordance with the pro-
posed structure.
725, 698. H NMR spectrum, δ, ppm (J, Hz): 7.53 (1H, s,
NH); 7.37–7.27 (5H, m, H Ph); 4.61–4.51 (2H, m, CH2Ph);
4.02 (2H, s, CH2CO); 3.25–3.07 (2H, m, SCH2); 3.07–2.70
(2H, m, SCH2); 1.37 (3H, t, J = 7.4, CH3); 1.20 (3H, t, J = 7.2,
CH3). 13C NMR spectrum, δ, ppm: 170.2 (C=O); 161.7
(C=N); 138.3 (C Ph); 128.7 (2CH Ph); 127.4 (3CH Ph);
55.3 (CH2CO); 43.1 (CH2Ph); 26.5 (SCH2); 25.8 (SCH2);
15.1 (CH3); 13.7 (CH3). Mass-spectrum, m/z: 297 [M+H]+.
Found, %: C 56.64; H 6.46; N 9.66; S 21.45. C14H20N2OS2.
Calculated, %: C 56.72; H 6.80; N 9.45; S 21.63.
In conclusion, we developed an efficient eco-friendly
method for the synthesis of imidazolin-4-one derivatives by
using microwave irradiation starting from methyl glycinate.
All the intermediate imino ester derivatives and almost all
imidazolin-4-one derivatives were synthesized for the first
time. This eco-friendly protocol can provide a suitable way
for synthesizing new potentially bioactive imidazolin-4-one
derivatives.
Di(n-propyl) [2-(benzylamino)-2-oxoethyl]carbonodi-
thioimidate (9c). IR spectrum, ν, cm–1: 3377 (N–H), 3033,
2962, 2923, 2870, 2843, 1752, 1730 (C=O), 1668, 1571
(C=N), 1513, 1451, 1425, 1398, 1291, 1212, 1159, 1115,
Experimental
IR spectra were recorded on a PerkinElmer Spectrum
GX FTIR spectrometer in KBr pellets. H and 13C NMR
1
1
spectra were recorded on a Bruker AV-250 spectrometer
(250 and 63 MHz, respectively) in CDCl3, internal standard
TMS. 13C NMR spectra of all synthesized compounds were
registered in DEPT-135 mode, 13C NMR spectra of
compounds 9a–d, 10a–d – additionally in DEPT-90 mode.
Mass spectra (ESI) were recorded on a Agilent Techno-
logies 1100 Series LC/MSD-Trap-SL spectrometer. Elemental
analyses were performed on a vario MACRO cube CHNS
element analyzer. All reagents and solvents were purchased
from commercial suppliers and used without further
purification. All microwave experiments were carried out
using a monomode Anton Paar Monowave 300 microwave
reactor (2.45 GHz, 850 W) in G4 microwave process vials
(4 ml). Reaction temperatures were monitored by an IR sensor.
Starting compounds 8a–d were prepared from methyl
glycinate (6) by the known procedure.27
1033, 942, 876, 743, 699. H NMR spectrum, δ, ppm
(J, Hz): 7.50 (1H, s, NH); 7.37–7.27 (5H, m, H Ph); 4.57–
4.51 (2H, m, CH2Ph); 4.03 (2H, s, CH2CO); 3.06 (2H, t,
J = 7.3, SCH2); 2.85 (2H, t, J = 7.3, SCH2); 1.81–1.67 (2H,
m, CH2CH2CH3); 1.67–1.45 (2H, m, CH2CH2CH3); 1.02
(3H, t, J = 7.4, CH3); 0.83 (3H, t, J = 7.3, CH3). 13C NMR
spectrum, δ, ppm: 169.9 (C=O); 161.7 (C=N); 137.9
(C Ph); 128.4 (2CH Ph); 127.3 (3CH Ph); 55.0 (CH2CO);
42.9 (CH2Ph); 33.8 (SCH2); 33.2 (SCH2); 23.1 (CH2CH2CH3);
21.8 (CH2CH2CH3); 13.2 (CH3); 13.0 (CH3). Mass-spectrum,
m/z: 325[M+H]+. Found, %: C 59.04; H 7.36; N 8.96;
S 19.35. C16H24N2OS2. Calculated, %: C 59.22; H 7.45;
N 8.63; S 19.76.
Di(n-butyl) [2-(benzylamino)-2-oxoethyl]carbonodithio-
imidate (9d). IR spectrum, ν, cm–1: 3382 (N–H), 3068,
3029, 2967, 2923, 2870, 2852, 1748, 1681 (C=O), 1672,
1571 (C=N), 1513, 1464, 1460, 1433, 1402, 1380, 1358,
1309, 1274, 1106, 1075, 1031, 942, 902, 862, 800, 738,
Synthesis of compounds 9a–h (General method).
Methyl N-[bis(alkylsulfanyl)methylidene]glycinate 8a–d
(4.0 mmol) and benzyl-, n-butyl-, or n-pentylamine
(4.1 mmol) were placed in a microwave process vial. The
mixture was irradiated at 100°C for 30 min, then cooled by
an air flow. The resulting yellow oil was chromatographed
on a silica gel column using EtOAc–hexane, 1:4, as eluent.
Compounds 9a–h were obtained in a form of light-yellow
oils. The yields are given in Table 1.
Dimethyl [2-(benzylamino)-2-oxoethyl]carbonodithio-
imidate (9a). IR spectrum, ν, cm–1: 3379 (N–H), 3086,
3061, 3028, 3001, 2960, 2924, 2866, 1666 (C=O), 1578
(C=N), 1518, 1497, 1454, 1427, 1400, 1360, 1319, 1261,
1074, 1043, 1028, 1001, 962, 922, 800, 735, 700, 499.
1H NMR spectrum, δ, ppm: 7.59 (1H, s, NH*); 7.38–7.26
(5H, m, H Ph); 4.62–4.51 (2H, m, CH2Ph); 4.02 (2H, s,
CH2CO); 2.58 (3H, s, SCH3); 2.33 (3H, s, SCH3). 13C NMR
spectrum, δ, ppm: 170.2 (C=O); 162.9 (C=N); 138.4
(C Ph); 128.7 (2CH Ph); 127.4 (3CH Ph); 55.1 (CH2CO);
43.1 (CH2Ph); 14.8 (2SCH3). Mass-spectrum, m/z: 269 [M+H]+.
Found, %: C 53.64; H 5.86; N 10.76; S 23.35. C12H16N2OS2.
Calculated, %: C 53.70; H 6.01; N 10.44; S 23.89.
1
699. H NMR spectrum, δ, ppm (J, Hz): 7.50 (1H, s, NH);
7.36–7.28 (5H, m, H Ph); 4.55–4.53 (2H, m, CH2Ph); 4.03
(2H, s, CH2CO); 3.07 (2H, t, J = 7.3, SCH2); 2.88 (2H, t,
J = 7.4, SCH2); 1.71–1.64 (2H, m, CH2CH2CH2CH3); 1.55–
1.49 (2H, m, CH2CH2CH2CH3); 1.47–1.39 (2H, m,
(CH2)2CH2CH3); 1.27–1.21 (2H, m, (CH2)2CH2CH3); 0.94
(3H, t, J = 7.3, CH3); 0.83 (3H, t, J = 7.3, CH3). 13C NMR
spectrum, δ, ppm: 170.2 (C=O); 162.0 (C=N); 138.2 (C Ph);
128.7 (2CH Ph); 127.4 (3CH Ph); 55.3 (CH2CO); 43.2
(CH2Ph); 31.9 (2SCH2); 31.3 (CH2CH2CH2CH3); 30.7
(CH2CH2CH2CH3);
22.1
((CH2)2CH2CH3);
21.8
((CH2)2CH2CH3); 13.6 (CH3); 13.5 (CH3). Mass-spectrum,
m/z: 353 [M+H]+. Found, %: C 61.64; H 8.26; N 7.96;
S 18.25. C18H28N2OS2. Calculated, %: C 61.32; H 8.01;
N 7.95; S 18.19.
Dimethyl [2-(n-butylamino)-2-oxoethyl]carbonodithio-
imidate (9e). IR spectrum, ν, cm–1: 3370 (N–H), 2965,
2928, 2867, 1671 (C=O), 1572 (C=N), 1490, 1451, 1427,
1360, 1317, 1271, 1075, 1028, 1001, 962, 804, 745.
1H NMR spectrum, δ, ppm (J, Hz): 7.26 (1H, s, NH); 3.94
(2H, s, CH2CO); 3.38–3.32 (2H, m, NHCH2); 2.58 (3H, s,
SCH3); 2.41 (3H, s, SCH3); 1.56–1.30 (4H, m,
CH2CH2CH2CH3); 0.94 (3H, t, J = 7.3, (CH3)3CH3).
13C NMR spectrum, δ, ppm: 170.0 (C=O); 162.5 (C=N);
55.2 (CH2CO); 38.7 (NHCH2); 31.6 (CH2CH2CH2CH3);
20.1 ((CH2)2CH2CH3); 14.7 (2SCH3); 13.8 ((CH2)3CH3).
Mass-spectrum, m/z: 235 [M+H]+. Found, %: C 46.34;
Diethyl [2-(benzylamino)-2-oxoethyl]carbonodithio-
imidate (9b). IR spectrum, ν, cm–1: 3379 (N–H), 3283,
3064, 3033, 2971, 2928, 2856, 1756, 1742, 1730, 1681,
1655 (C=O), 1578 (C=N), 1566, 1518, 1452, 1438, 1398,
1349, 1305, 1263, 1177, 1079, 1057, 1028, 960, 937, 752,
* In compounds 9a–h proton NH is exchangable by D2O heated at 85°C.
155

Chemistry of Heterocyclic Compounds 2018, 54(2), 153–157
H 7.46; N 11.90; S 27.20. C9H18N2OS2. Calculated, %:
(C=N), 1492, 1455, 1430, 1422, 1344, 1331, 1275, 1171,
1070, 1025, 1017, 974, 881, 727, 701, 655. 1H NMR
spectrum, δ, ppm: 7.40–7.24 (5H, m, H Ph); 4.66 (2H, s,
CH2Ph); 4.19 (2H, s, CH2CO); 2.51 (3H, s, SCH3).
13C NMR spectrum, δ, ppm: 180.0 (C=O); 163.9 (C=N);
135.6, 128.7, 128.0, 127.9 (C Ar); 59.0 (CH2CO); 44.0
(CH2Ph); 12.6 (SCH3). Mass-spectrum, m/z: 221 [M+H]+.
Found, %: C 60.04; H 5.46; N 12.96; S 14.45. C11H12N2OS.
Calculated, %: C 59.98; H 5.49; N 12.72; S 14.56.
C 46.12; H 7.74; N 11.95; S 27.36.
Diethyl [2-(n-butylamino)-2-oxoethyl]carbonodithio-
imidate (9f). IR spectrum, ν, cm–1: 3375 (N–H), 2979,
2925, 2854, 1751, 1720, 1680, 1665 (C=O), 1570 (C=N),
1565, 1455, 1448, 1390, 1375, 1263, 1079, 1055, 1028,
1
752, 724, 690. H NMR spectrum, δ, ppm (J, Hz): 7.26
(1H, s, NH); 3.95 (2H, s, CH2CO); 3.37–3.31 (2H, m,
NHCH2); 3.14–2.96 (4H, m, 2SCH2); 1.57–1.30 (10H, m,
2SCH2CH3, CH2CH2CH2CH3); 0.93 (3H, t, J = 7.2,
(CH3)3CH3). 13C NMR spectrum, δ, ppm: 170.1 (C=O);
161.4 (C=N); 55.3 (CH2CO); 38.7 (NHCH2); 31.7
(CH2CH2CH2CH3); 26.5 (SCH2); 25.8 (SCH2); 20.0
(CH2CH2CH2CH3); 15.1 (CH3); 13.8 (CH3); 13.7 (CH3).
Mass-spectrum, m/z: 263 [M+H]+. Found, %: C 50.54;
H 8.46; N 10.96; S 24.25. C11H22N2OS2. Calculated, %:
C 50.34; H 8.45; N 10.67; S 24.44.
3-Benzyl-2-(ethylsulfanyl)-3,5-dihydro-4H-imidazol-
4-one (10b). IR spectrum, ν, cm–1: 3055, 3032, 2971, 2966,
2930, 2879, 1730 (C=O), 1643, 1605, 1562 (C=N), 1492,
1457, 1420, 1346, 1330, 1265, 1208, 1076, 1057, 1004,
1
966, 930, 827, 757, 730, 704, 647. H NMR spectrum,
δ, ppm: 7.38–7.22 (5H, m, H Ph); 4.65 (2H, s, CH2Ph);
4.19 (2H, s, CH2CO); 3.16–3.10 (2H, m, SCH2); 1.41–1.30
(3H, m, CH3). 13C NMR spectrum, δ, ppm: 179.9 (C=O);
163.3 (C=N); 135.7, 128.7, 128.0, 127.9 (C Ar); 58.9
(CH2CO); 44.0 (CH2Ph); 24.8 (SCH2); 14.2 (CH3). Mass-
spectrum, m/z: 235 [M+H]+. Found, %: C 61.64; H 6.26; N
11.86; S 13.52. C12H14N2OS. Calculated, %: C 61.51; H
6.02; N 11.96; S 13.68.
Di(n-propyl) [2-(n-butylamino)-2-oxoethyl]carbonodi-
thioimidate (9g). IR spectrum, ν, cm–1: 3373 (N–H), 2962,
2923, 2870, 2843, 1752, 1720 (C=O), 1666, 1570 (C=N),
1515, 1455, 1428, 1290, 1154, 1111, 942, 870, 740, 697.
1H NMR spectrum, δ, ppm: 7.26 (1H, s, NH); 3.96 (2H, s,
CH2CO); 3.37–3.32 (2H, m, NHCH2); 3.09–2.94 (4H, m,
3-Benzyl-2-(n-propylsulfanyl)-3,5-dihydro-4H-imidazol-
4-one (10c). IR spectrum, ν, cm–1: 3040, 2977, 2928, 2851,
1671 (C=O), 1663, 1650, 1633, 1628, 1560 (C=N), 1490,
1455, 1427, 1343, 1065, 1018, 877, 655. 1H NMR
spectrum, δ, ppm: 7.37–7.22 (5H, m, H Ph); 4.66 (2H, s,
CH2Ph); 4.17 (2H, s, CH2CO); 3.13–3.08 (2H, m, SCH2);
1.77–1.71 (2H, m, CH2CH2CH3); 1.02–0.98 (3H, m, CH3).
13C NMR spectrum, δ, ppm: 179.9 (C=O); 163.4 (C=N);
135.6, 128.6, 127.9, 127.8 (C Ar); 58.9 (CH2CO); 43.9
(CH2Ph); 32.1 (SCH2); 22.2 (CH2CH2CH3); 13.3 (CH3).
Mass-spectrum, m/z: 249 [M+H]+. Found, %: C 62.74;
H 6.46; N 11.16; S 12.85. C13H16N2OS. Calculated, %:
C 62.87; H 6.49; N 11.28; S 12.91.
2SCH2);
1.78–1.31
(8H,
m,
2SCH2CH2CH3,
CH2CH2CH2CH3); 1.05–0.91 (9H, m, 3CH3). 13C NMR
spectrum, δ, ppm: 170.2 (C=O); 161.6 (C=N); 55.4
(CH2CO); 38.7 (NHCH2); 34.1 (CH2); 33.5 (CH2); 31.7
(CH2); 23.4 (CH2); 22.2 (CH2); 20.1 (CH2); 13.7 (CH3);
13.6 (CH3); 13.3 (CH3). Mass-spectrum, m/z: 291 [M+H]+.
Found, %: C 53.64; H 9.46; N 9.96; S 22.25. C13H26N2OS2.
Calculated, %: C 53.75; H 9.02; N 9.64; S 22.08.
Di(n-butyl) [2-(n-butylamino)-2-oxoethyl]carbonodi-
thioimidate (9h). IR spectrum, ν, cm–1: 3380 (N–H), 2965,
2920, 2868, 2848, 1745, 1672 (C=O), 1565 (C=N), 1520,
1462, 1435, 1384, 1350, 1319, 1106, 1078, 1031, 867, 804,
1
730, 695. H NMR spectrum, δ, ppm (J, Hz): 7.50 (1H, s,
3-Benzyl-2-(n-butylsulfanyl)-3,5-dihydro-4H-imidazol-
4-one (10d). IR spectrum, ν, cm–1: 3063, 2968, 2939, 2852,
2362, 2331, 1718 (C=O), 1641, 1575 (C=N), 1499, 1465,
NH); 4.03 (2H, s, CH2CO); 3.36–3.30 (2H, m, NHCH2);
3.07 (2H, t, J = 7.2, SCH2); 2.88 (2H, t, J = 7.2, SCH2);
1.71–1.65 (2H, m, CH2); 1.55–1.49 (4H, m, 2CH2); 1.45–
1.41 (4H, m, 2CH2); 1.28–1.20 (2H, m, CH2); 1.06–0.99
(3H, m, CH3); 0.94 (3H, t, J = 7.3, CH3); 0.83 (3H, t,
J = 7.3, CH3). 13C NMR spectrum, δ, ppm: 170.1 (C=O);
161.7 (C=N); 55.3 (CH2CO); 38.7 (NHCH2); 31.9 (CH2);
31.6 (CH2); 31.3 (CH2); 30.8 (2CH2); 22.2 (CH2); 21.8
(CH2); 20.1 (CH2); 13.7 (CH3); 13.6 (CH3); 13.5 (CH3).
Mass-spectrum, m/z: 319 [M+H]+. Found, %: C 56.64;
H 9.46; N 8.96; S 20.05. C15H30N2OS2. Calculated, %:
C 56.56; H 9.49; N 8.79; S 20.13.
1
1440, 1388, 1355, 1222, 1167, 1071, 1012, 619. H NMR
spectrum, δ, ppm: 7.40–7.24 (5H, m, H Ph); 4.64 (2H, s,
CH2Ph); 4.16 (2H, s, CH2CO); 3.15–3.10 (2H, m, SCH2);
1.71–1.65 (2H, m, CH2CH2CH2CH3); 1.45–1.39 (2H, m,
(CH2)2CH2CH3); 0.95–0.89 (3H, m, CH3). 13C NMR
spectrum, δ, ppm: 179.9 (C=O); 163.3 (C=N); 135.6, 128.6,
127.8, 127.6 (C Ar); 58.8 (CH2CO); 43.9 (CH2Ph); 30.7
(SCH2); 29.9 (CH2CH2CH2CH3); 21.8 ((CH2)2CH2CH3);
13.5 (CH3). Mass-spectrum, m/z: 263 [M+H]+. Found, %:
C 64.14; H 6.96; N 10.76; S 12.25. C14H18N2OS. Calcu-
lated, %: C 64.09; H 6.92; N 10.68; S 12.22.
Synthesis of compounds 10a–h (General method).
Dithioimidate 9a–h (2.0 mmol) was placed in a microwave
process vial and irradiated at 150°C for 60 min. The
reaction mixture was cooled by air flow. The resulting
yellow oil was chromatographed on a silica gel column
using EtOAc–hexane, 1:4, as eluent. Compounds 10a–h were
obtained in a form of light-yellow oils. The yields are given
in Table 1.
3-(n-Butyl)-2-(methylsulfanyl)-3,5-dihydro-4H-imidazol-
4-one (10e). IR spectrum, ν, cm–1: 2964, 2924, 2866, 1660
(C=O), 1571 (C=N), 1520, 1490, 1450, 1420, 1365, 1312,
1
1265, 1075, 1040, 1038, 965, 921, 745, 495. H NMR
spectrum, δ, ppm (J, Hz): 4.16 (2H, s, CH2CO); 3.48–3.40
(2H, m, CH2(CH2)2CH3); 2.47 (3H, s, SCH3); 1.66–1.40
(4H, m, CH2(CH2)2CH3); 1.05–0.93 (3H, m, (CH2)3CH3).
13C NMR spectrum, δ, ppm: 179.9 (C=O); 163.4 (C=N); 58.9
(CH2CO); 38.5 (CH2(CH2)2CH3); 30.1 (CH2CH2CH2CH3);
20.3 ((CH2)2CH2CH3); 12.6 (SCH3); 13.7 ((CH2)3CH3).
3-Benzyl-2-(methylsulfanyl)-3,5-dihydro-4H-imidazol-
4-one (10a). IR spectrum, ν, cm–1: 3088, 3080, 3035, 2960,
2945, 2858, 2341, 1737, 1732, 1688 (C=O), 1643, 1562
156

Chemistry of Heterocyclic Compounds 2018, 54(2), 153–157
Mass-spectrum, m/z: 187 [M+H]+. Found, %: C 51.64;
H 7.46; N 15.06; S 17.25. C8H14N2OS. Calculated, %:
C 51.58; H 7.58; N 15.04; S 17.21.
References
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3-(n-Butyl)-2-(ethylsulfanyl)-3,5-dihydro-4H-imidazol-
4-one (10f). IR spectrum, ν, cm–1: 2978, 2938, 2856, 1742,
1681, 1659 (C=O), 1572 (C=N), 1560, 1515, 1450, 1440,
1395, 1341, 1300, 1175, 1070, 1054, 1018, 937, 742, 720, 692.
1H NMR spectrum, δ, ppm (J, Hz): 4.16 (2H, s, CH2CO);
3.43 (2H, t, J = 7.3, CH2(CH2)2CH3); 2.99–2.95 (2H, m,
SCH2); 1.64–1.42 (4H, m, CH2(CH2)2CH3); 1.40 (3H, t,
J = 7.3, SCH2CH3); 0.98 (3H, t, J = 7.3, (CH2)3CH3).
13C NMR spectrum, δ, ppm: 179.8 (C=O); 163.2 (C=N);
58.7 (CH2CO); 38.4 (CH2(CH2)2CH3); 31.7 (CH2CH2CH2CH3);
25.5 (SCH2CH3); 20.0 ((CH2)2CH2CH3); 14.1 (SCH2CH3);
13.7 ((CH2)3CH3). Mass-spectrum, m/z: 201 [M+H]+.
Found, %: C 53.84; H 8.26; N 13.96; S 16.15. C9H16N2OS.
Calculated, %: C 53.97; H 8.05; N 13.99; S 16.01.
3-(n-Butyl)-2-(n-propylsulfanyl)-3,5-dihydro-4H-imidazol-
4-one (10g). IR spectrum, ν, cm–1: 2933, 2878, 2840, 1739
(C=O), 1579 (C=N), 1520, 1450, 1420, 1395, 1217, 1169,
1119, 1034, 940, 877, 733, 695. 1H NMR spectrum, δ, ppm
(J, Hz): 4.15 (2H, s, CH2CO); 3.42 (2H, t, J = 7.3,
CH2(CH2)2CH3); 2.98 (2H, t, J = 7.3, SCH2); 2.02–1.96
(2H, m, SCH2CH2CH3); 1.62–1.40 (4H, m, CH2(CH2)2CH3);
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(CH2)3CH3). 13C NMR spectrum, δ, ppm: 179.8 (C=O);
163.2 (C=N); 58.6 (CH2CO); 38.7 (CH2(CH2)2CH3); 33.5
(SCH2); 31.7 (CH2CH2CH2CH3); 22.2 (SCH2CH2CH3);
20.1 ((CH2)2CH2CH3); 13.7 ((CH2)3CH3); 13.3 (S(CH2)2CH3).
Mass-spectrum, m/z: 215 [M+H]+. Found, %: C 56.14;
H 8.46; N 13.16; S 14.95. C10H18N2OS. Calculated, %:
C 56.04; H 8.47; N 13.07; S 14.96.
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The work was supported by Artvin Coruh University
research project (BAP-2012.F19.02.24) and Hellenic
Republic Ministry of Education, State Scholarships
Foundation (I.K.Y.) of Greece (Grant No. 1211). We thank
the NMR center at the University of Ioannina for the
spectra.
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157