Facile synthesis of 2-alkylthio-5-phenylmethylene-4H-imidazol-4-ones

Article abstract of DOI:10.1002/hc.10160

The facile synthesis of 2-alkylthio-5-phenylmethylene-4H-imidazol-4-ones was discussed. Using reagents like RI and BrCH₂COR the alkylation reaction was carried out at room temperature, while it was carried out at 50°C-60°C with other reagents. The stretching mode of C=C showed relatively strong absorption at about 1635 cm^-1.

Full text of DOI:10.1002/hc.10160

Heteroatom Chemistry
Volume 14, Number 4, 2003
Facile Synthesis of 2-Alkylthio-5-
phenylmethylene-4H-imidazol-4-ones
Yong Sun1 and Ming-Wu Ding2
1Department of Chemistry, Yunyang Teachers College, Danjiangkou Hubei 442700, People’s
Republic of China
2Institute of Organic Synthesis, Central China Normal University, Wuhan Hubei 430079, People’s
Republic of China
Received 8 February 2003
a new efficient synthesis of 5-arylmethylene-2-
ABSTRACT: 2-Alkylthio-5-phenylmethylidene-4H-
alkyl(aryl)thioimidazolones from the stable vinylim-
imidazol-4-ones 4 were synthesized by S-alkylation
inophosphorane 1.
of 2-thioxo-3-alkyl(aryl)-4-imidazolidinones 3, which
O
O
were obtained via cyclization of isothiocyanates 2
1
1
R
2
R
2
1
2
1
2
3
4
R X
3
R
R
R
3
R NH
2
R
R
CO H
2
R
CO H
2
ꢀ
C
CSCl
2
N
N
with aliphatic(aromatic) primary amines.
2003
R
R
HN
N
NCS
NH
2
Wiley Periodicals, Inc. Heteroatom Chem 14:348–351,
2003; Published online in Wiley InterScience (www.
interscience.wiley.com). DOI 10.1002/hc.10160
4
SR
S
(1)
INTRODUCTION
RESULTS AND DISCUSSION
4H-Imidazol-4-ones are important heterocycles hav-
ing biological and pharmaceutical activities [1–
3], and some 2-alkylthioimidazolones show sig-
nificant fungicidal activities [4–6]. However, most
of the 2-alkylthioimidazolones reported are of
the 5,5-disubstituted type and are generally syn-
thesized from corresponding ꢀ-amino acetic acid
[6,7] (Eq. (1)). Unfortunately, 5-arylmethylene-2-
alkylthioimidazolones cannot be prepared by this
general method for the corresponding starting ma-
terial needed would be unstable vinyl amino acetic
acids. Recently, we were interested in the syn-
thesis of biologically active imidazolones via tan-
dem aza-Wittig reaction [8–10]. Herein we report
The easily accessible vinyliminophosphorane 1 re-
acted with carbon disulfide to give vinyl isothio-
cyanate 2. The reaction of 2 with aliphatic primary
amines took place smoothly at room temperature to
give 2-thioxo-4-imidazolidinones 3 in 75–96% yields.
The reaction of 2 with aromatic primary amines had
to be carried out in refluxing acetonitrile in the pres-
ence of potassium carbonate (Eq. (2)). The crystal
color of 3 is yellow, and other data of the prepara-
tion of 3 are listed in Table 1.
O
COOEt
N=C=S
COOEt
N=PPh
RNH
R
2
CS
2
N
Ph
N
H
Ph
Ph
3
S
3
2
1
(2)
Correspondence to: Yong Sun; e-mail: sunyong6111@sina.com.
Contract grant sponsor: National Natural Science Foundation
of China.
S-Alkylation of 3e with alkyl halides in pres-
ence of potassium carbonate provided 2-alkylthio-5-
phenylmethylidene-4H-imidazol-4-ones 4 in 65–98%
Contract grant number: Project No. 20102001.
c
ꢀ
2003 Wiley Periodicals, Inc.
348

Facile Synthesis of 2-Alkylthio-5-phenylmethylene-4H-imidazol-4-ones 349
about 1635 cm−1 because of resonance effect. The
MS spectrum of 4a shows molecule ion peak at m/z
308 with 87% abundance.
TABLE 1 Preparation of 3-Substituted-2-thioxo-4-imidazo-
lidinones 3 from Vinyl Isothiocyanate 2
Yield
R
Formula
Condition (%)a mp ( ◦C)
EXPERIMENTAL
3a
3b
3c
3d
3e
Me
i -Bu
n-C5H11
n-C8H17
PhCH2
C11H10N2OS
C14H16N2OS
rt/30 min 75 207–208
rt/10 min 84 154–155
Melting points are uncorrected. MS were measured
on a HP5988A spectrometer. IR were recorded on
a PE-983 infrared spectrometer as KBr pellets.
NMR were recorded in CDCl3 on a Varian XL-200
spectrometer and resonances are given relative to
TMS. Elemental analyses were taken on a Perkin-
Elmer 2400 CHN Elementary Analysis Instrument.
CS2 is poisonous and a good hood should be
used.
C15 18
C18 24
C17 14
H
H
H
N2OS
N2OS
N2OS
rt/15 min 91
rt/10 min 83
98–99
81–82
rt/10 min 96 228–229
3f CH2CH2OH C12 12
3g 3-Me-Ph 17H14N2OS
3h 3-Cl-2-Me-Ph C17 13
3i 4-EtO-Ph
H N2O2S rt/50 min 79 105–107
C
80◦C/2 h 50 181–182
H
N2OClS 80◦C/3 h 52 200–201
C
18H16N2O2S 80◦C/2 h 79 195–196
aIsolated yields based on vinyliminophosphorane 1.
yields. With alkylating reagents such as RI and
BrCH2COR, the alkylation could be carried out at
room temperature. With other reagents, the alkyla-
tion had to be carried out at 50–60◦C (Eq. (3)). The
crystal color of 4 is light yellow, and other data of the
alkylation of 3e are listed in Table 2.
Preparation of Vinyliminophosphorane 1
Vinyliminophosphorane 1 was prepared by the
Staudinger reaction of vinyl azide and triphenyl
phosphine according to [11], m.p. 148–150◦C (Lit.
[11] m.p. 149◦C).
O
O
CH Ph
2
CH Ph
2
RX
CO (s)
Ph
N
Ph
N
(3)
HN
3e
N
K
2
3
S
SR
Preparation of 3-Alkyl-2-thioxo-4-imidazolidin-
4
ones 3a–f from Vinyl Isothiocyanate 2
The structures of 3 and 4 have been character-
To a solution of vinyliminophosphorane 1 [12]
(2.25 g, 5 mmol) in dry methylene chloride (15
ml) was added excess carbon disufide (5 ml). Af-
ter the reaction mixture was refluxed for 28 h, the
solvent was removed under reduced pressure and
ether/petroleum ether (1:2, 20 ml) was added to pre-
cipitate triphenylphosphine sulfide, which was re-
moved by filtration. The filtrate was evaporated to
give isothiocyanate 2, which was used directly with-
out further purification. To a solution of crude 2 in
ized spectroscopically, and their data are listed in
1
Tables 3 and 4, respectively. For example, the H
NMR spectral data in 4a show the signals of CH,
CH2Ph, and SCH3 at δ = 6.96, 4.77, and 2.68 ppm
as single absorption. The chemical shift of aryl hy-
drogen multiplets is 8.13–7.21 ppm. In the IR spectra
of 4a, the strong stretching mode absorption of imi-
dazolone C O appear at 1712 cm−1. The stretching
mode of C C shows relatively strong absorption at
TABLE 2 Alkylation of 3e to 2-Alkylthio-4H-imidazol-4-ones 4
Yield
RX
Formula
Condition
(%)a
mp ( ◦C)
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
MeI
EtBr
n-PrBr
n-BuBr
i -BuBr
n-C6H13Br
PhCH2Cl
ClCH2CN
C18H16N2OS
rt/3 h
90
90
95
81
65
67
87
88
95
85
95
98
69
76
127–128
112–113
97–98
83–84
83–85
C
19H18N2OS
C20 20N2OS
21H22N2OS
21H22N2OS
50◦C/3 h
60◦C/3 h
50◦C/3 h
60◦C/4 h
50◦C/3 h
50◦C/2 h
50◦C/2 h
rt/2 h
H
C
C
C23 26
C24 20
C19 15
C25 20
C19 17
C20 18
C21 20
C22 22
C22 22
H
H
H
H
H
H
H
H
N2OS
N2OS
N3OS
N2O2S
N3O2S
N2O3S
N2O3S
N2O3S
N2O3S
54–55
141–142
156–158
180–181
202–203
144–145
113–114
79–81
PhCOCH2Br
ClCH2CONH2
BrCH2COOMe
ClCH2COOEt
BrCH2CH2COOEt
BrCH(CH3)COOEt
50◦C/2 h
rt/2 h
50◦C/2 h
50◦C/3 h
60◦C/2 h
H
108–109
aIsolated yields based on 2-thioxo-4-imidazolidinone 3e.

350 Sun and Ding
TABLE 3 Elemental Analysis, IR, MS, and 1H NMR Data of 2-Thioxo-4-imidazolidinones 3
Anal. % (Calc.)
IR (cm−1
)
MS (m/z, %)
1H-NMR (CDCl3, δ)
3a
3b
3c
3d
3e
3f
C, 60.81 (60.55)
H, 4.78 (4.59)
N, 13.11 (12.84)
C, 64.60 (64.62)
H, 6.21 (6.15)
N, 11.04 (10.77)
C, 65.93 (65.69)
H, 6.86 (6.57)
N, 10.41 (10.22)
C, 68.41 (68.35)
H, 7.83 (7.59)
N, 9.05 (8.86)
C, 69.55 (69.39)
H, 5.03 (4.76)
N, 9.79 (9.52)
C, 58.29 (58.06)
H, 5.10 (4.84)
N, 11.56 (11.29)
3248
1705
1647
3254
1708
1649
3257
1706
1647
3253
1707
1648
3250
1704
1643
3445
3259
1711
1650
3234
1747
1644
3229
1747
1645
3225
1746
1643
218 (M+, 4), 201 (100),
183 (94), 167 (52), 152
(56), 116 (53), 108 (82)
260 (M+, 21), 227 (3), 203
(30), 160 (17), 117
3.34 (s, 3H), 6.72 (s, 1H), 7.08–8.11
(m, 5H), 8.81 (s, 1H)
0.96 (d, 6H), 2.29 (m, 1H), 3.72
(d, 2H), 6.68 (s, 1H), 7.23–7.44
(m, 5H), 8.81 (s, 1H)
0.93 (t, 3H), 1.27–1.75 (m, 6H), 3.88
(t, 2H), 6.68 (s, 1H), 7.23–7.42
(m, 5H), 8.82 (s, 1H)
(100), 89 (26)
274 (M+, 2), 241 (13), 218
(19), 203 (2), 117 (81),
89 (88), 73 (100)
316 (M+, 6), 283 (100),
203 (10), 160 (18), 117
(43), 90 (11)
0.87 (t, 3H), 1.25–1.70 (m, 12H),
3.87 (t, 2H), 6.67 (s, 1H),
7.23–7.43 (m, 5H), 8.82 (s, 1H)
5.08 (s, 2H), 6.71 (s, 1H), 7.00–7.81
(m, 5H), 8.71 (s, 1H)
294 (M+, 97), 265 (8), 261
(21), 203 (4), 148 (52),
117 (64), 91 (100)
248 (M+, 3), 230 (3), 203
(2), 160 (6), 117 (30),
89 (29), 44 (100)
2.48 (s, 1H), 3.88 (t, 2H), 4.11
(t, 2H), 6.71 (s, 1H), 7.23–7.45
(m, 5H), 8.83 (s, 1H)
3g
3h
3i
C, 69.66 (69.39)
H, 5.01 (4.74)
N, 9.78 (9.52)
C, 62.38 (62.10)
H, 4.25 (3.96)
N, 8.49 (8.52)
C, 66.66 (66.67)
H, 5.15 (4.94)
N, 8.92 (8.64)
294 (M+, 16), 265 (2), 189
(10), 148 (17), 116 (73),
102 (24), 89 (100)
2.38 (s, 3H), 6.79 (s, 1H), 7.12–7.58
(m, 9H), 9.00 (s, 1H)
328 (M+, 90), 313 (30),
295 (98), 232 (73), 117
(99), 89 (94), 32 (100)
324 (M+, 100), 295 (34),
291 (8), 237 (19), 180
(67), 160 (65), 117 (97)
2.19 (s, 3H), 6.81 (s, 1H), 7.05–7.47
(m, 8H), 9.23 (s, 1H)
1.43 (t, 3H), 4.04 (q, 2H), 6.78
(s, 1H), 6.93–7.43 (m, 9H), 9.14
(s, 1H)
TABLE 4 Elemental Analysis, IR, MS, and 1H NMR Data of 2-Alkylthio-4H-imidazol-4-ones 4
Anal. % (Calc.)
IR (cm−1
)
MS (m/z, %)
1H-NMR (CDCl3, δ)
4a
4b
4c
4d
4e
4f
C, 70.41 (70.13)
H, 5.45 (5.19)
N, 9.36 (9.09)
C, 70.06 (70.81)
H, 5.88 (5.59)
N, 8.99(8.70)
1712
1635
308 (M+, 87), 293 (8), 275
(31), 218 (73), 203 (22),
117 (80), 91 (100)
2.68 (s, 3H), 4.77 (s, 2H), 6.96
(s, 1H), 7.21–8.13 (m, 10H)
1712
1636
322 (M+, 87), 294 (27), 289
(11), 200 (9), 116 (21),
91 (100)
1.46 (t, 3H), 3.30 (q, 2H), 4.74 (s, 2H),
6.94 (s, 1H), 7.20–8.11 (m, 10H)
C, 71.19 (71.43)
H, 6.22 (5.95)
N, 8.58 (8.33)
C, 72.23 (72.00)
H, 6.57 (6.29)
N, 8.27 (8.00)
C, 72.25 (72.00)
H, 6.54 (6.29)
N, 8.23 (8.00)
C, 70.27 (70.02)
H, 7.11 (6.88)
N, 7.69 (7.41)
C, 74.96 (75.00)
H, 5.01 (5.21)
N, 7.55 (7.29)
C, 68.20 (68.47)
H, 4.25 (4.50)
N, 12.50 (12.61)
1711
1634
336 (M+, 79), 308 (5), 303
(28), 294 (94), 148 (64),
116 (75), 91 (100)
1.05 (t, 3H), 1.84 (m, 2H), 3.26
(t, 2H), 4.74 (s, 2H), 6.93 (s, 1H),
7.19–8.12 (m, 10H)
0.97 (t, 3H), 1.48 (m, 2H), 1.79
(m, 2H), 3.29 (t, 2H), 4.75 (s, 2H),
6.94 (s, 1H), 7.20–8.13 (m, 10H)
1.04 (d, 6H), 2.10 (m, 1H), 3.18
(d, 2H), 4.75 (s, 2H), 6.93
(s, 1H), 7.18–8.12 (m, 10H)
0.89 (t, 3H), 1.35–1.82 (m, 8H), 3.28
(t, 2H), 4.76 (s, 2H), 6.94 (s, 1H),
7.21–8.10 (m, 10H)
1713
1636
350 (M+, 42), 321 (3), 317
(16), 303 (60), 294 (80),
116 (50), 91 (100)
1713
1635
350 (M+, 50), 335 (7), 317
(15), 294 (65), 261 (50),
116 (63), 91 (100)
1711
1637
378 (M+, 93), 349 (10),
345 (31), 331 (40), 294
(100), 289 (80), 90 (99)
384 (M+, 89), 350 (6), 293
(53), 206 (40), 160 (44),
116 (48), 91 (100)
4g
4h
1712
1636
4.53 (s, 2H), 4.74 (s, 2H), 6.98
(s, 1H), 7.20–8.15 (m, 15H)
2253
1715
1637
333 (M+, 69), 300 (10), 293
(29), 188 (41), 160 (27),
116 (54), 91 (100)
4.01 (s, 2H), 4.73 (s, 2H), 7.07
(s, 1H), 7.20–8.10 (m, 10H)
(Continued)

Facile Synthesis of 2-Alkylthio-5-phenylmethylene-4H-imidazol-4-ones 351
TABLE 4 Continued
Anal. % (Calc.)
IR (cm−1
)
MS (m/z, %)
1H-NMR (CDCl3, δ)
4i
C, 73.03 (72.82)
H, 5.11 (4.85)
N, 7.07 (6.80)
C, 65.24 (64.96)
H, 5.11 (4.84)
N, 12.25 (11.97)
1716
1699
1638
3317
3271
1714
1679
1634
1734
1713
1636
1738
1713
1635
1745
1712
1633
1741
1713
1636
412 (M+, 13), 380 (4), 307
(21), 294 (5), 116 (12),
105 (79), 91 (100)
4.75 (s, 2H), 4.82 (s, 2H), 6.91
(s, 1H), 7.06–8.06 (m, 15H)
4j
351 (M+, 20), 307 (9), 294
(19), 215 (9), 148 (15),
116 (21), 91 (100)
3.90 (s, 2H), 4.78 (s, 2H), 5.08
(s, 2H), 6.70 (s, 1H), 7.04–7.99
(m, 10H)
4k
4l
C, 65.79 (65.57)
H, 5.11 (4.92)
N, 7.88 (7.65)
C, 66.02 (66.32)
H, 5.11 (5.26)
N, 7.10 (7.37)
C, 66.96 (67.00)
H, 5.85 (5.58)
N, 7.40 (7.11)
C, 66.87 (67.00)
H, 5.80 (5.58)
N, 7.34 (7.11)
366 (M+, 64), 333 (41), 307
(46), 293 (53), 188 (62),
160 (59), 91 (100)
3.75 (s, 3H), 4.01 (s, 2H), 4.77
(s, 2H), 6.96 (s, 1H), 7.21–8.08
(m, 10H)
380 (M+, 64), 347 (18), 335
(19), 307 (53), 293 (51),
188 (64), 91 (100)
1.28 (t, 3H), 4.01 (s, 2H), 4.21 (q, 2H),
4.79 (s, 2H), 6.96 (s, 1H),
7.21–8.06 (m, 10H)
4m
4n
394 (M+, 57), 361 (36), 349
(32), 321 (40), 303 (19),
294 (58), 91 (100)
1.25 (t, 3H), 2.91 (t, 2H), 3.53 (t, 2H),
4.15 (q, 2H), 4.74 (s, 2H), 6.96
(s, 1H), 7.21–8.10 (m, 10H)
1.24 (t, 3H), 1.68 (d, 3H), 4.18
(q, 2H), 4.60–4.86 (m, 3H), 6.95
(s, 1H), 7.20–8.09 (m, 10H)
394 (M+, 86), 361 (31), 349
(22), 321 (32), 293 (91),
188 (50), 91 (100)
CH3CN (15 ml) was added RNH2 (5 mmol). The mix-
ture was allowed to stand for 10–50 min at room
temperature and the precipitated solid was collected
and washed with water and ethanol, recrystallized
from methylene chloride/petroleum ether to give 3-
alkyl-2-thioxo-4-imidazolidinone 3a–f.
tallized from methylene chloride/petroleum ether to
give 2-alkylthio-4H-imidazol-4-ones 4.
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To the solution of 2 in CH3CN (15 ml) was added
ArNH2 (5 mmol) and solid potassium carbonate
(0.05 g). The mixture was stirred for 2–3 h at refluxing
temperature and filtered; the filtrate was then evap-
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A mixture of 3e (1.18 g, 4 mmol), alkyl halide
(5 mmol), and solid potassium carbonate (1.11 g,
8 mmol) in CH3CN (30 ml) was stirred for 2–4 h
at room temperature or 50–60◦C and filtered, the
filtrate was condensed and the residue was recrys-