Synthesis of 2-thioxoimidazolines via reaction of 1-unsubstituted 3-aminoquinoline-2,4-diones with isothiocyanates

Article abstract of DOI:10.1016/j.tet.2009.09.048

3-Alkyl/aryl-3-amino-1H,3H-quinoline-2,4-diones react with alkyl/aryl isothiocyanates to give 3a-alkyl/aryl-1,2,3,3a-tetrahydro-9b-hydroxy-2-thioxo-5H-imidazo[4,5-c]quinolin-4(9bH)-ones in high yields. These compounds rearrange in boiling acetic acid or c

Full text of DOI:10.1016/j.tet.2009.09.048

Tetrahedron 65 (2009) 9103–9115
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Tetrahedron
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Synthesis of 2-thioxoimidazolines via reaction of 1-unsubstituted
3-aminoquinoline-2,4-diones with isothiocyanates
a
a,
b,
c
d,
c
e
*
ꢀ
ˇ
´
´
´
´
ˇ
ˇ´
ˇ
˚
Zdenka Pruckova , Antonın Klasek , Antonın Lycka , Ivan Miksık , Ales Ruzicka
a Department of Chemistry, Faculty of Technology, Tomas Bata University, 762 72 Zl´ın, Czech Republic
b Research Institute for Organic Syntheses (VUOS), Rybitv´ı 296, 533 54 Pardubice 20, Czech Republic
c
´
´
´
´
´
University of Hradec Kralove, Faculty of Education, Rokitanskeho 62, CZ 500 03 Hradec Kralove 3, Czech Republic
d Department of Physiology, Academy of Sciences of the Czech Republic, 142 20 Prague, Czech Republic
e Department of General and Inorganic Chemistry, Faculty of Chemical Technology, University of Pardubice, 53210 Pardubice, Czech Republic
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 30 June 2009
Received in revised form 24 August 2009
Accepted 10 September 2009
Available online 15 September 2009
3-Alkyl/aryl-3-amino-1H,3H-quinoline-2,4-diones react with alkyl/aryl isothiocyanates to give 3a-alkyl/
aryl-1,2,3,3a-tetrahydro-9b-hydroxy-2-thioxo-5H-imidazo[4,5-c]quinolin-4(9bH)-ones in high yields.
These compounds rearrange in boiling acetic acid or concd hydrochloric acid to give novel 4-(2-ami-
nophenyl)-1H-imidazole-2(3H)-thiones, 1,3-bis(2-(2,3-dihydro-2-thioxo-1H-imidazol-5-yl)phenyl)ureas
and minor N-(2-(2,3-dihydro-2-thioxo-1H-imidazol-4-yl)phenyl)acetamides. In the presence of ethanol,
the starting compounds rearrange in boiling acetic acid to give ethyl 2-(2,3-dihydro-2-thioxo-1H-imid-
azol-4-yl)phenylcarbamates. All compounds were characterized by their 1H, 13C, IR and MS spectra and
some of them also by 15N NMR data. The structures of two compounds were supported by single-crystal
X-ray diffraction.
Keywords:
a
-Aminoketones
1,3-Diphenylureas
Rearrangement
Thiones
Ó 2009 Elsevier Ltd. All rights reserved.
Thiourea derivatives
1. Introduction
substituents at the 1, 3 and 10 positions of the starting compounds 1.
Thus, according to this criterion, we divided the starting 3-amino-
In our laboratory, much attention has been paid to the reactivity
of 3-amino, 3-hydroxy and 3-thiocyanato-1H,3H-quinoline-2,4-
diones. Recently, the behaviour of the products of the reaction of
3-amino-1H,3H-quinoline-2,4-diones with isocyanic acid and iso-
cyanates was investigated. In an acidic medium, these compounds
are subject to molecular rearrangement, leading to novel hetero-
cycles. A brief survey of these transformations was given in our last
paper on this topic.1
The exceptional structural diversity of the products of the mo-
lecular rearrangement mentioned above gave us incentive to
perform the analogous reaction of 3-amino-1H,3H-quinoline-2,4-
diones with isothiocyanates and to examine how the products of
this reaction would behave in an acidic environment. We antici-
pated the formation of new compounds containing a sulfur atom,
which may be interesting, since many biologically active com-
pounds contain a sulfur atom.2,3
1H,3H-quinoline-2,4-diones into three different groups.4 The first
group contained compounds substituted at the 1-position with an
alkyl or aryl groups and at the 3-position with an alkyl group. In our
latest paper,4 we demonstrated that compounds of this group
afforddcontrary to their reaction with isocyanatesda single cyclic
addition product, which rearranges in an acidic environment to
give three different types of spiro-imidazoline-4,30-[3H]indole-
2,20(1H0)-diones, depending on the substituents at the 3 and 3a
positions.
S
R3
S
C-NHR3
1
O
O
N
3
HO
NHR2
R1
N
N
R1
9b
R2
R2
R3NCS
CHCl3
R3NCS
CHCl3
3a
4
R1
O
7
N
H
O
N
N
H
O
6
H
2
1
3
The structure of the rearrangement products of the adducts of 1
with isocyanates is largely dependent on the character of the
Key of substituents:
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
R1
R2
R3
Bu Bu Ph Ph Bu Bu Ph Ph Bu Bu Ph Ph Bu Bu Ph Ph
Me Me Me Me Bu Bu Bu Bu Bz Bz Bz Bz
H
H
H
H
Me Ph Me Ph Me Ph Me Ph Me Ph Me Ph Me Ph Me Ph
* Corresponding author. Tel.: þ420 576 031 413; fax: þ420 577 210 722.
Scheme 1.
´
E-mail address: klasek@ft.utb.cz (A. Klasek).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.09.048

´
Z. Pruckova et al. / Tetrahedron 65 (2009) 9103–9115
9104
In this work, we demonstrate that the reaction of starting
2. Results and discussion
compounds 1 of the third group (compounds unsubstituted at the
1-position) also provides a single cyclic adduct, 3, which rearranges
in an acidic environment to give novel 4-(2-aminophenyl)-1H-
imidazole-2(3H)-thiones (4), 1,3-bis(2-(2,3-dihydro-2-thioxo-1H-
imidazol-5-yl)phenyl)ureas (6) and minor N-(2-(2,3-dihydro-2-
thioxo-1H-imidazol-4-yl)phenyl)acetamides (7) (Scheme 1).
Reactions of 3-amino-1H,3H-quinoline-2,4-diones 1 with iso-
thiocyanates were performed by refluxing the reaction compo-
nents in chloroform (Scheme 1).
Methylisothiocyanate and phenylisothiocyanate were chosen as
model isothiocyanates. Starting aminoketones 1 were obtained
from the corresponding 3-chloro derivatives, in accordance with
the procedures described.5
As in the reaction of the 1-substituted compounds 1 with iso-
thiocyanates,4 only cyclic 1,2,3,3a-tetrahydro-9b-hydroxy-2-thi-
oxo-5H-imidazo[4,5-c]quinolin-4(9bH)-ones 3 were isolated in
good to very good yields (Scheme 1, Table 1). No single isomeric
acyclic 3-thioureido-1H,3H-chinolin-2,4-dione 2 was isolated. The
formation of tautomeric compounds bearing an SH group (theo-
retically possible in the case of 3a–d) was not detected. Signals of
the thioxo group of compounds 3 lie in the narrow region of 181.8–
183.4 ppm of the 13C NMR spectra, which is typical of the C]S
group. The values of 1J (15N, 1H)¼90 and 98.8 Hz in the 15N NMR
spectrum of 3a also exclude the presence of the C–SH group in this
compound. The characteristic signals of C-3a in the 13C NMR
spectra of compounds 3 occur in the region of 68.1–78.3 ppm. For
complete assignation of all signals in the 1H and 13C NMR spectra of
compounds 3 to the corresponding atoms see Supplementary data.
We have found that 2-oxa-analogues6 of compounds 3 rear-
range to form two different types of products, through boiling in
either acetic acid or concd hydrochloric acid.7 Therefore, both of
these reaction media were now used here also for the rearrange-
ment of compounds 3 (Scheme 2).
Table 1
Preparation of compounds 3 by the reaction of 3-aminoquinoline-2,4(1H,3H)-diones
(1) with isothiocyanates
Entry
Educt
Substituentsa
Product (yield, %)
R1
R2
R3
1
2
3
4
5
6
7
8
1a
1a
1c
1c
1e
1e
1g
1g
1i
Bu
Bu
Ph
Ph
Bu
Bu
Ph
Ph
Bu
Bu
Ph
Ph
Bu
Bu
Ph
Ph
H
H
H
H
Me
Ph
Me
Ph
Me
Ph
Me
Ph
Me
Ph
Me
Ph
Me
Ph
Me
Ph
3a (92)
3b (80)
3c (85)
3d (98)
3e (82)
3f (97)
3g (77)
3h (93)
3i (83)
3j (96)
3k (74)
3l (60)
3m (74)
3n (96)
3o (76)
3p (88)
Me
Me
Me
Me
Bu
Bu
Bu
Bu
Bz
Bz
Bz
Bz
9
10
11
12
13
14
15
16
1i
1k
1k
1m
1m
1o
1o
a
R3 from isothiocyanate.
The results are presented in Table 2. A comparison of the IR,
NMR and MS spectra of the rearrangement products of 3 showed
that three different types of products were formed. The first group
of products consisted of 2-thioxoimidazolines 4, which are single
products of the rearrangement of 3 in concd hydrochloric acid
(Method B), but also formed, to a lesser degree, in acetic acid
(Method A).
In the IR spectra of compounds 4, two absorption bands appear
in the region of 3404–3476 and 3308–3378 cmꢀ1; these bands are
characteristic of a primary amino group in o-substituted anilines.8
In the 13C NMR spectra (Table 3), the characteristic signals of the
C]S group appeared in the region of 160.1–164.1 ppm; these sig-
nals are approximately 10 ppm downfield of the 13C NMR spectra
peaks of the respective 2-oxa-analogues.7,9 In the case of
S
S
S
2
R3
R3
R3
CSNHR2
N
R3
N
N
4
HO
R2
N
R2
N
5
R1
R2
N
N
6´
H+
R1
H2O
R1
1´
2´
R1
N=C=O
- CO2
- H2O
N
H
O
3
N
H
NH2
5
A
4
AcOH
AcOH
EtOH
S
S
5´
O
R3
2
R3
2
2´´
2´
1´´
1
N
1
N
4
N
R2
N
5
R2
N
N
H
6´
6´
1´
4
H
5
5
4
1´
2´
NHCOOC2H5
R1
R1
1´
2´
1
N
2
R3
R3
R1
R1
N
N
N
NHCOCH3
6
R2
R2
8
7
S
S
Scheme 2.
Table 2
Molecular rearrangement of compounds 3 in boiling AcOH (Method A), concd hydrochloric acid (Method B) and acetic acid/ethanol (9:1) (Method C)a
Entry
Educt
Method
Time (h)
Products (yield, %)
Entry
Educt
Method
Time (h)
Products (yield, %)
1
2
3
4
5
6
7
8
3a
3a
3b
3b
3c
3c
3c
3d
3d
3e
3e
3f
A
B
A
B
A
B
C
A
B
A
B
A
B
A
B
A
B
A
2
2
1.5
2
1
1
1
1.5
1
2
1.5
2.5
2.5
2
1
2.5
1
4a (22), 6a (29), 7a (3)
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
3i
3j
3j
3k
3k
3k
3l
3l
3l
3m
3m
3n
3n
3o
3o
3p
3p
B
A
B
A
B
C
A
B
C
A
B
A
B
A
B
A
B
2.5
1.5
1
1
1
1
1
1
1
1.5
0.5
2
2
1.5
1
4i (56)
4j (5), 6j (15)
4j (52)
4k (25), 6k (26)
4k (55)
8k (58)
4l (18), 6l (40), 7l (4)
4l (50)
8l (51)
4m (12), 6m (17)
4m (86)
4n (17), 6n (20), 7n (8)
4n (53)
4a (60)
b
4b (49)
4c (7), 6c (33)
4c (69)
8c (74)
b
9
4d (50)
4e (6), 6e (25)
4e (43)
4f (28), 6f (41), 7f (6)
4f (76)
4g (41), 6g (24), 7g (10)
4g (76)
4h (2), 6h (65), 7h (4)
4h (76)
4i (28), 6i (23)
10
11
12
13
14
15
16
17
18
3f
3g
3g
3h
3h
3i
4o (21), 6o (45), 7o (1)
4o (69)
4p (7), 6p (37)
4p (71)
2
2
2
a
For key of substituents see Table 1 and Scheme 1.
Inseparable mixtures of several compounds were obtained.
b

´
Z. Pruckova et al. / Tetrahedron 65 (2009) 9103–9115
9105
Table 3
1H and 13C chemical shifts (
d, ppm) of compounds 4a–p in DMSO-d6
Position
4a
4b
4c
4d
4e
4f
4g
4h
dH
dC
dH
dC
dH
dC
dH
dC
dH
dC
dH
dC
dH
dC
dH
dC
2 (C]S)
4
d
160.1
123.8
125.6
111.9
148.1
114.9
130.2
115.9
132.0
d
d
161.7
124.0
126.7
112.0
147.9
114.5
129.7
115.4
132.4
d
d
161.5
124.5
124.6
112.2
148.3
115.0
130.8
116.3
131.9
d
d
163.0
125.0
125.3
112.1
148.4
114.5
130.4
115.5
132.5
d
d
161.3
123.5
127.1
111.6
148.2
114.8
130.3
115.8
132.0
d
d
162.8
123.6
128.1
111.7
148.1
114.4
129.8
115.2
132.5
d
d
161.9
124.9
127.9
111.8
148.6
114.7
130.4
115.7
132.3
d
d
161.7
125.0
128.6
111.4
148.4
114.2
130.0
115.0
132.8
d
d
d
d
d
d
d
d
d
5
d
d
d
d
d
d
d
d
10
d
d
d
d
d
d
d
d
20
d
d
d
d
d
d
d
d
30
6.77
7.15
6.62
6.95
5.00
2.31
2.23
1.48
1.20
0.79
12.15
3.19
d
6.58
6.95
6.38
6.77
5.07
2.36
2.27
1.54
1.24
0.82
12.40
d
6.83
7.21
6.63
6.99
5.22
d
6.58
7.00
6.40
6.89
5.26
d
6.64
7.18
6.80
6.99
5.07
2.45
2.38
1.42
1.24
0.79
3.58
3.26
d
6.51
6.90
6.33
6.74
5.07
2.44
2.35
1.43
1.18
0.74
3.59
d
6.71
7.12
6.52
6.96
5.23
d
6.44
6.90
6.31
6.90
5.25
d
40
50
60
NH2
10 (R1)
23.4
23.6
128.8
128.7
23.1
23.3
128.6
128.8
20 (R1)
30 (R1)
40 (R1)
10 (R2)
10 (R3)
20 (R3)
30 (R3)
40 (R3)
30.3
21.4
13.6
d
30.0
21.6
13.6
d
7.40
7.28
7.21
12.71
3.23
d
125.5
128.5
127.2
d
7.47
7.30
7.21
12.90
d
125.7
128.5
128.1
d
30.3
21.6
13.5
31.8
32.1
d
29.9
21.7
13.5
32.0
137.2
128.5
128.2
127.7
7.38
7.38
7.38
3.50
3.22
d
129.9
128.5
128.6
33.2
32.1
d
129.9
a
a
a
b
b
3.58
d
33.4
31.2
d
137.0
128.5
128.1
127.6
31.1
d
136.7
129.0
128.2
127.4
137.2
a
b
7.30
7.30
7.26
7.30
7.30
7.26
7.24
7.24
7.24
a
a
b
b
d
d
d
d
d
d
d
d
d
d
d
d
d
d
d
d
Position
4i
4j
4k
4l
4m
4n
4o
4p
dH
dC
dH
dC
dH
dC
dH
dC
dH
dC
dH
dC
dH
dC
dH
dC
2 (C]S)
4
d
160.8
123.8
126.7
111.7
148.1
114.8
130.3
115.9
132.0
d
d
162.3
123.8
127.5
111.8
147.9
114.4
129.8
115.3
132.4
d
d
161.2
125.2
127.6
111.6
148.5
114.7
130.3
115.7
132.5
d
d
162.7
125.1
128.4
111.4
148.2
114.2
129.9
115.0
132.9
d
d
162.2
124.3
127.0
111.5
148.2
114.9
130.4
115.9
132.0
d
d
163.9
124.2
128.1
112.0
147.4
114.8
130.0
115.8
132.5
d
d
162.6
125.6
127.8
111.4
148.5
114.7
130.4
115.7
132.5
d
d
164.1
125.6
128.5
111.3
148.2
114.2
130.0
115.0
132.9
d
d
d
d
d
d
d
d
d
5
d
d
d
d
d
d
d
d
10
d
d
d
d
d
d
d
d
20
d
d
d
d
d
d
d
d
30
6.79
7.18
6.64
6.99
5.05
2.47
2.38
1.43
1.22
0.77
4.02
6.59
6.96
6.39
6.80
5.10
2.50
2.44
1.46
1.24
1.02
4.10
6.68
7.09
6.51
6.97
5.18
d
6.41
6.86
6.31
6.93
5.18
6.80
7.17
6.63
7.00
5.10
2.34
2.24
1.07
1.02
0.58
5.54
5.37
d
6.62
6.99
6.43
6.86
5.14
2.42
2.31
1.09
1.02
0.58
5.70
5.40
d
6.70
7.11
6.51
6.99
5.24
6.43
6.87
6.30
6.96
5.19
40
50
60
NH2
10 (R1)
23.0
23.2
128.8
128.8
23.2
23.5
128.4
128.6
20 (R1)
30 (R1)
40 (R1)
10 (R2)
30.9
21.4
13.5
44.4
30.6
21.7
13.8
44.6
7.40
7.40
7.40
4.09
3.96
1.56
130.3
128.4
128.7
44.6
130.3
30.4
21.4
13.3
47.7
30.1
21.6
13.3
47.9
130.2
128.2
128.7
48.2
130.1
a
a
a
c
c
c
d
d
d
b
e
b
e
4.15
4.01
1.66
1.62
1.20
0.78
d
44.8
5.49
5.20
d
5.63
5.24
d
48.4
20 (R2)
1.76
30.3
1.88
1.79
1.46
0.78
d
30.2
29.9
29.8
137.3
137.3
137.0
137.2
30 (R2)
40 (R2)
50 (R2)
10 (R3)
20 (R3)
30 (R3)
40 (R3)
1.43
0.98
d
19.6
13.8
d
19.7
13.4
d
1.16
0.75
d
19.3
13.4
d
19.3
13.4
d
7.34
7.39
7.31
3.39
d
126.7
128.5
127.2
32.4
d
126.9
7.10
127.0
128.2
127.0
32.4
d
127.0
f
f
f
d
d
d
g
c
e
g
c
e
3.24
d
31.9
d
d
137.2
128.4
128.1
127.7
3.32
d
32.1
d
d
a
137.1
d
f
137.2
3.40
d
d
d
136.9
b
g
e
7.30
7.30
7.30
a
a
b
b
f
f
g
g
d
d
e
e
d
d
d
d
d
d
d
d
d
d
d
d
d
d
d
d
a
d
¼7.30–7.53.
b
c
d
e
f
d
¼128.8, 128.6, 128.4, 128.2, 128.0.
d
¼7.08–7.28.
¼7.14–7.47.
¼128.6, 128.4, 128.3, 128.2.
¼7.30–7.41.
d
d
d
g
d
¼128.7, 128.6, 128.5, 128.3, 127.9.
compounds 4k and 4l, the structure was confirmed by single-
crystal X-ray diffraction techniques (Figs. 1 and 2).
The variety of molecular rearrangement products of 3 in acetic
acid (Method A) is much more heterogeneous. In most cases, the
main products are 1,3-bis(ureas) 6 (Table 2), which are structurally
analogous to compounds isolated from the rearrangement of ad-
ducts of 1 with isocyanates.7,9 Compounds 6 arise from the addition
of compounds 4 to isocyanate intermediate A (Scheme 2). Un-
fortunately, the rearrangement of compounds 3b and 3d provides
complicated mixtures of at least five compounds each. The pres-
ence of corresponding compounds 6b and 6d was proved by NMR.
However, these compounds could not be separated.
Both compounds crystallized in the triclinic space group P-1.
Views of the molecular structures of both compounds (Figs.1 and 2)
show a perfectly planar arrangement of the five-membered core
rings. Also, the substituting atoms reside in the same plane. The
bond distances within these are shorter than standard single bond
distances, and this is attributable to the conjugated character of the
rings.10 Moreover, the C1–S1 distances and the geometry of the
respective groups are closest in character to a double bond.
The formation of compounds 4 can be smoothly elucidated from
the hydrolysis of the isocyanate intermediate A, which arises via
opening of the quinolone ring of 1 (Scheme 2).
APCI mass spectrometry allows for the identification of the
molecular weights of compounds 6. These mass spectra provide
complementary ions in both polarity modes and are useful for the

´
9106
Z. Pruckova et al. / Tetrahedron 65 (2009) 9103–9115
Table 4
Selected 1H and 13C chemical shifts (
d, ppm) of compounds 6 in DMSO-d6
Compound
dH (NHCONH)
dC (NHCONH)
dC (C]S)
6a
6c
6e
6f
6g
6h
6i
6j
6k
6l
8.19, 8.17
8.18, 8.06
8.25, 8.18
8.22, 8.09
8.26, 8.06
8.14, 8.10
8.14, 8.10
8.21, 8.05
8.12, 8.02
8.00, 7.96
8.28, 8.18
8.29, 8.11
8.23, 8.08
8.05, 7.97
152.90, 152.88
152.51, 152.48
152.82, 152.62
152.06, 151.79
152.34, 152.30
151.36, 151.33
152.80, 152.66
152.08, 151.91
152.24, 152.11
151.28, 151.25
152.63, 151.59
151.99, 151.83
152.20, 152.11
151.33, 151.28
160.88, 161.80
161.98, 161.95
161.87, 161.85
163.34. 163.06
162.56, 161.48
163.67, 161.62
161.35, 161.28
162.79, 162.55
161.92, 161.88
163.22, 163.04
162.76. 162.58
164.21, 164.03
163.07, 163.04
164.37, 164.31
6m
6n
6o
6p
To our surprise, we did not observe formation of the indole type
compounds (5) during rearrangement of 3 in refluxing acetic acid.
In the case of the molecular rearrangement of the oxa-analogues of
compounds 3, the oxa-analogues of compounds 5 were all isolated
and their interconversion with the oxa-analogues of 4 was evi-
dent.7,9 It is clear that the 2-thioxoimidazoline ring of compounds 4
is, in comparison with the imidazolone ring, much more resistant to
nucleophilic attack of the amino group at the 5-position. The for-
mation of minor compounds 7 is in agreement with this finding;
the NMR spectra for compounds 7 are presented in Table 5. These
compounds likely form from the acetylation of anilines 4 (Scheme
2). The alternative way to form these compounds is through the
decomposition of the mixed anhydride of acetic and carbamoic
acids, which can arise from the addition of acetic acid to isocyanate
intermediate A. An analogous pathway is also possible for the for-
mation of 6 from intermediate A and compound 4.
Figure 1. Molecular structure of compound 4k with atom numbering scheme. (ORTEP
50% probability level), arbitrary spheres for hydrogen atoms.
For confirmation of the proposed isocyanate reaction mecha-
nism for the rearrangement of compounds 3, we carried out their
rearrangements in acetic acid in the presence of ethanol (Table 2,
Method C). The only isolated products of this reaction were carba-
moic esters 8, whose origin can be explained by alcoholysis of in-
termediate A or by alcoholysis of the mixed anhydride, formed from
intermediate A and acetic acid. NMR spectra of compounds 8 are
presented in Table 5. Compounds 7 and 8 have also been prepared
by acylation of compounds 4.
3. Conclusions
In conclusion, the described molecular rearrangement of com-
pounds 3 is not merely interesting from a theoretical point of view
but, owing to the simple reaction protocol, presents an easy path-
way for the preparation of novel heterocyclic systems containing
2-thioxoimidazoline fragment. A number of 2-thioxoimidazolines
and their derivatives exhibit significant biological activities11,12 in-
cluding inflammatory activity,13 gentamycin nephrotoxicity,14 dop-
Figure 2. Molecular structure of compound 4l with atom numbering scheme. (ORTEP
50% probability level), arbitrary spheres for hydrogen atoms.
determination and identification of alkyl/aryl substitution, such as
the neutral losses of butene for butyl substitution. Another typical
neutral loss is NCS fragment (or the appropriate alkyl/aryl-NCS). In
the case of the compounds herein, the cleavage of the N–C bond in
the –NH–CO–NH– group gave two series of ions labelled as [F]þ and
[Fþ26]þ in the positive-ion spectra (also the [Fþ26þN]þ ion was
found), whereas the corresponding analogues in the negative-ion
spectra are labelled as [Fꢀ2H]ꢀ and [Fþ26–2H]ꢀ. These series were
described in a previous paper.7
amine
b-hydroxylase inhibitory activity and anti-aggregating
activity against collagen.15 Therefore, it may be assumed that the
compounds described in this paper should also display significant
biological activity.
The NMR spectra of compounds 6 are very complex. The signals
of the two components differ only slightly, both in the proton and
carbon NMR spectra, and have a relative integral ratio near 1:1. This
is a consequence of the co-occurrence of two E,E-syn and E,E-anti
conformers, described earlier for their oxa-analogues.7 Due to large
number of atoms and the very strong overlap of appropriate pairs of
signals in compounds 6, complete assignment of all resonances was
difficult and, in some cases, almost impossible. Therefore, charac-
terization of only selected signals for compounds 6 is presented in
Table 4.
4. Experimental
4.1. General considerations
Melting points were determined on a Kofler block or Gallen-
camp apparatus. Elemental analyses (C, H, N) were performed with
an EA 1108 Elemental Analyzer (Fisons Instrument). IR (KBr)
spectra were recorded on a Mattson 3000 spectrophotometer. NMR
spectra were recorded on
a Bruker Avance spectrometer
(500.13 MHz for 1H, 125.76 MHz for 13C, 50.68 MHz for 15N) in

Table 5
1H and 13C chemical shifts (
d, ppm) of compounds 7 and 8 in DMSO-d6
Position
7a
7f
7g
7h
7l
7n
7o
8c
8k
8l
dH
dC
dH
dC
dH
dC
dH
dC
dH
dC
dH
dC
dH
dC
dH
dC
dH
dC
dH
dC
2 (C]S)
4
d
160.4
122.9
125.8
121.5
137.8
124.7
129.4
124.6
132.0
23.4
d
163.1
122.5
128.4
119.8
137.8
123.1
129.0
123.5
132.3
23.1
d
162.4
123.9
128.0
120.0
137.9
123.9
129.0
124.2
132.3
128.3
d
163.5
123.8
128.2
118.7
137.7
122.2
129.7
123.1
132.5
128.9
d
163.1
124.0
128.4
118.8
137.6
d
163.9
123.4
128.0
120.8
137.6
123.9
129.1
123.9
132.3
23.3
d
163.0
124.9
127.5
120.9
137.8
124.3
129.7
124.5
132.4
128.2
d
161.6
123.8
124.8
121.6
138.3
124.1
130.3
124.6
132.2
128.5
d
161.5
124.5
127.7
120.5
138.1
123.6
129.7
123.9
132.5
128.5
d
162.7
d
d
d
d
d
d
d
d
d
d
124.3
a
5
d
d
d
d
d
d
d
d
d
d
10
d
d
d
d
d
d
d
d
d
d
119.3
137.8
122.2
129.1
122.7
132.5
128.7
20
d
d
d
d
d
d
d
d
d
d
30
7.80
7.45
7.28
7.32
2.24
2.14
1.48
1.19
0.78
12.23
7.84
7.24
6.95
7.00
2.51
2.41
1.49
1.22
0.77
3.68
7.79
7.38
7.17
7.30
d
7.74
7.15
6.87
7.05
d
7.69
7.14
6.87
7.08
d
122.4
7.70
7.23
6.97
6.97
2.34
2.24
1.14
0.99
0.55
5.64
5.53
7.62
7.37
7.20
7.41
d
7.75
7.52
7.22
7.34
d
7.60
7.35
7.11
7.27
d
7.40
7.14
6.86
7.14
d
b
40
50
123.1
132.5
128.5
60
10 (R1)
20 (R1)
30 (R1)
40 (R1)
10 (R2)
29.9
21.5
13.5
d
29.6
21.7
13.4
32.2
7.30
7.38
7.38
3.52
129.7
128.6
128.7
33.2
129.7
130.0
29.9
21.5
13.2
47.8
129.7
128.3
128.4
48.1
7.25
7.25
7.25
12.75
125.7
128.4
128.0
d
7.37
7.37
7.37
4.04
3.94
1.56
1.17
0.74
d
130.4
128.4
128.8
44.6
d
130.6
c
c
c
d
d
d
e
e
e
f
f
f
g
b
a
g
b
a
3.61
33.4
4.29
44.9
5.40
5.31
d
e
4.18
3.97
1.64
1.20
0.78
d
44.8
d
20 (R2)
30 (R2)
40 (R2)
50 (R2)
1 (R3)
d
d
d
d
d
d
d
d
d
d
d
d
d
d
1.66
1.23
0.82
d
29.9
19.3
13.4
d
d
h
137.0
137.1
126.7
128.3
127.1
33.1
d
d
d
29.9
19.2
13.4
d
29.9
19.3
13.4
d
d
d
d
d
d
d
126.7
d
d
h
h
g
e
e
d
d
d
d
d
d
d
d
d
d
d
d
d
d
127.2
d
d
3.21
d
31.6
d
d
137.1
128.6
128.2
127.8
168.5
23.8
d
3.34
d
32.8
d
d
c
137.0
d
d
136.9
d
h
137.2
3.44
d
3.23
d
31.6
d
3.31
d
32.5
d
d
f
137.0
2 (R3)
7.28
7.28
7.28
9.29
2.07
d
g
b
i
a
3 (R3)
d
d
d
d
d
d
d
d
d
d
c
c
g
g
d
d
b
b
h
h
i
i
f
f
a
a
4 (R3)
d
d
d
d
d
d
d
d
d
d
NHCO
COCH3
CH2CH3
CH2CH3
9.36
2.01
d
168.5
23.5
d
9.26
1.92
d
168.2
23.6
d
9.15
1.90
d
167.8
23.8
d
9.14
1.94
d
167.8
23.9
d
9.38
2.01
d
168.4
23.6
d
9.32
1.90
d
167.9
23.4
d
9.16
d
154.0
d
9.17
d
153.9
d
9.12
d
153.4
d
3.97
1.12
60.2
14.5
4.04
1.26
60.3
14.6
4.02
1.28
60.1
14.7
d
d
d
d
d
d
d
d
d
d
d
d
d
d
a
d
¼129.0, 128.6, 128.4, 128.1, 127.9.
¼129.1, 128.9, 128.7, 128.6, 128.3, 128.0.
¼7.28–7.49.
¼7.28–7.45.
¼7.06–7.42.
¼7.28–7.45.
b
c
d
e
f
d
d
d
d
d
g
h
i
d
¼128.9, 128.8, 128.7, 128.6, 128.3, 128.1.
¼7.26–7.45.
¼128.9, 128.6, 128.3, 127.9.
d
d

´
Z. Pruckova et al. / Tetrahedron 65 (2009) 9103–9115
9108
DMSO-d6. 1H and 13C chemical shifts are given on the
and are referenced to internal TMS. 15N chemical shifts were re-
ferred to external neat nitromethane in co-axial capillary (
¼0.0).
d
scale (ppm)
4.3. General method for the preparation of 1,2,3,3a-
tetrahydro-9b-hydroxy-2-thioxo-5H-imidazo[4,5-c]quinolin-
4(9bH)-ones (3)
d
All 2D experiments (gradient-selected (gs)-COSY, gs-TOCSY, gs-
HMQC, gs-HMBC) were performed using manufacturer’s software.
Proton spectra were assigned using gs-COSY and, when necessary,
also TOCSY. Protonated carbons were assigned by gs-HMQC. Qua-
ternary carbons were assigned by gs-HMBC. The positive- and
negative-ion APCI mass spectra were measured on an ion trap
analyser Agilent LC-MSD Trap XCT-Ultra (Agilent, Palo Alto, CA,
USA) within the mass range m/z¼50–500. Samples were dissolved
Phenylisothiocyanate (0.144 mL, 1.2 mmol) or methyl iso-
thiocyanate (88 mg, 1.2 mmol) was added to the cooled (0 ꢁC) and
stirred solution of 1 (1 mmol) in chloroform (5 mL). In the case of
1c, 1,4-dioxane was used as solvent. The reaction mixture was
stirred overnight at room temperature and then heated to reflux
for 1 h. After cooling and evaporating in vacuo to dryness, the
residue was crystallized from appropriate solvent or column
chromatographed. For NMR spectra of compounds 3 see Supple-
mentary data.
in acetonitrile and analysed after direct injection (10
mL) at the flow
rate of 400 L/min acetonitrile. The ion source temperature was
m
350 ꢁC, the APCI probe temperature was 350 ꢁC, the flow rate and
the pressure of nitrogen were 4 L/min and 45 psi, respectively. For
MS/MS measurements, the isolation width of precursor ions was
4 m/z and the collision amplitude was 0.8 V. Column chromatog-
raphy was carried out on silica gel (Merck, grade 60, 70–230 mesh)
using chloroform and then successive mixtures of chloroform–
ethanol (in ratios from 99:1 to 8:2, solvent system S1) or benzene
and then successive mixtures of benzene–ethyl acetate (in ratios
from 99:1 to 8:2, solvent system S2). Reactions as well as the course
of separation and also the purity of substances were monitored by
TLC (elution systems benzene–ethyl acetate, 4:1 (S3), chloroform–
ethanol, 9:1 (S4) and/or 19:1 (S5), and chloroform–ethyl acetate,
7:3 (S6)) on AlugramÒ SIL G/UV254 foils (Macherey–Nagel).
4.3.1. 3a-Butyl-9b-hydroxy-1-methyl-1,2,3,3a-tetrahydro-2-thioxo-
5H-imidazo[4,5-c]quinolin-4(9bH)-one (3a). Compound was pre-
pared from 1a in 92% yield. Colourless crystals, mp 200–209 ꢁC
(benzene), IR: 3333, 3210, 3067, 2958, 2921, 2861, 1675, 1598, 1492,
1437,1404,1365,1331,1283,1227,1161,1123,1105, 1053,1044,1004,
975, 761, 682, 625, 572, 515 cmꢀ1
. Anal. Calcd (found) for
C15H19N3O2S: C 58.99 (58.82); H 6.27 (6.38); N 13.76 (13.65). Pos-
itive-ion APCI-MS: m/z 306 [MþH]þ (100%), 288 [MþH–H2S]þ;
positive-ion APCI-MS/MS of m/z 306: 233 [MþH–CH3NCS]þ (100%).
Negative-ion APCI-MS: m/z 304 [MꢀH]ꢀ (100%), 286 [MꢀH2O]ꢀ;
negative-ion APCI-MS/MS of m/z 304: 270 [MꢀH–H2S]ꢀ (100%), 231
[MꢀH–CH3NCS]ꢀ.
X-ray analysis. The X-ray data for colourless crystals of 4k and
4l (crystallized from a mixture of benzene and hexane) were
obtained at 150(1) K using Oxford Cryostream low-temperature
4.3.2. 3a-Butyl-9b-hydroxy-1-phenyl-1,2,3,3a-tetrahydro-2-thioxo-
5H-imidazo[4,5-c]quinolin-4(9bH)-one (3b). Compound was pre-
pared from 1a in 80% yield. Colourless crystals, mp 206–212 ꢁC
(ethyl acetate), IR: 3336, 3290, 3060, 2957, 2932, 2869, 1677, 1659,
1612, 1597, 1532, 1497, 1485, 1450, 1430, 1345, 1314, 1272, 1240,
device on a Nonius KappaCCD diffractometer with Mo K
ation (
¼0.71073 Å), a graphite monochromator and the
a
f
radi-
and
l
c
scan mode. Data reductions were performed with DENZO-
SMN.16 The absorption was corrected by integration methods.17
Structures were solved by direct methods (Sir92)18 and refined
by full matrix least-square based on F2 (SHELXL97).19 Hydrogen
atoms were mostly localized on a difference Fourier map,
however to ensure uniformity of treatment of crystal, all hy-
drogens were recalculated into idealized positions (riding
model) and assigned temperature factors Hiso(H)¼1.2 Ueq (pivot
atom) or of 1.5 Ueq for the methyl moiety with C–H¼0.96, 0.97,
0.86 and 0.93 Å for methyl, methylene, N–H and hydrogen atoms
in aromatic ring.
1183, 1161, 1112, 955, 867, 760, 723, 700, 668, 618, 586, 526 cmꢀ1
.
Anal. Calcd (found) for C20H21N3O2S: C 65.37 (65.47); H 5.76
(5.92); N 11.44 (11.30). Positive-ion APCI-MS: m/z 368 [MþH]þ
(100%), 336 [MþH–S]þ; positive-ion APCI-MS/MS of m/z 368: 233
[MþH–C6H5NCS]þ (100%). Negative-ion APCI-MS: m/z 366
[MꢀH]ꢀ (100%), 332 [MꢀH–H2S]ꢀ, 273 [MþH–C6H5NH2]þ, 231
[MꢀH–C6H5NCS]ꢀ; negative-ion APCI-MS/MS of m/z 366: 332
[MꢀH–H2S]ꢀ, 247 [MꢀH–C6H5–NCO]ꢀ, 231 [MꢀH–C6H5NCS]ꢀ
(100%).
Crystallographic data for 4l. C25H25N3S, M¼399.54, triclinic, P-1,
4.3.3. 9b-Hydroxy-1-methyl-3a-phenyl-1,2,3,3a-tetrahydro-2-thi-
oxo-5H-imidazo[4,5-c]quinolin-4(9bH)-one (3c). Compound was
prepared from 1c in 85% yield. Colourless crystals, mp 177–183 ꢁC
(ethyl acetate), IR: 3380, 3195, 3061, 2980, 2920, 1680, 1598, 1491,
1394, 1288, 1228, 1168, 1134, 1066, 1045, 976, 924, 894, 809, 759,
702, 654, 627, 588, 573 cmꢀ1. Anal. Calcd (found) for C17H15N3O2S: C
62.75 (62.59); H 4.65 (4.79); N 12.91 (12.88). Positive-ion APCI-MS:
m/z 326 [MþH]þ (68%), 308 [MþH–H2O]þ, 294 [MþH–S]þ (100%);
positive-ion APCI-MS/MS of m/z 326: 253 [MþH–CH3NCS]þ (100%),
236 [MþH–CH3NHCSNH2]þ. Negative-ion APCI-MS: m/z 324
[MꢀH]ꢀ (100%), 306 [MꢀH2O]ꢀ; negative-ion APCI-MS/MS of m/z
324: 306 [MꢀH2O]ꢀ, 290 [MꢀH2S]ꢀ (100%).
a¼9.0622(6), b¼11.3578(8), c¼11.8802(5),
a
¼66.213(4), ¼73.118(4),
b
g
m
¼85.825(5)ꢁ,
Z¼2,
V¼1069.30(11) Å3,
Dc¼1.241 g cmꢀ3
,
¼0.167 mmꢀ1, Tmin¼0.942, Tmax¼0.960; 21,596reflections measured
(
qmax¼27.5ꢁ), 4897 independent (Rint¼0.0925), 2582 with I>2
s(I), 262
parameters, S¼1.017, R1 (obs. data)¼0.0586, wR2 (all data)¼0.1077;
max, min residual electron density¼0.227, ꢀ0.317 e Åꢀ3
.
Crystallographic data for 4k. C20H23N3S, M¼337.47, triclinic, P-1,
a¼8.1161(12),
b¼8.8611(14),
c¼13.7078(16),
a
¼85.964(11),
b
¼87.909(12),
g
¼68.305(13)ꢁ, Z¼2, V¼913.7(3) Å3, Dc¼1.227 g cmꢀ3
,
m
¼0.183 mmꢀ1, Tmin¼0.926, Tmax¼0.969; 19,628 reflections measured
(
qmax¼27.5ꢁ), 4188 independent (Rint¼0.0866), 2555 with I>2
s(I), 217
parameters, S¼1.096, R1 (obs. data)¼0.0665, wR2 (all data)¼0.1146;
max, min residual electron density¼0.268, ꢀ0.287 e Åꢀ3
.
4.3.4. 1,3a-Diphenyl-9b-hydroxy-1,2,3,3a-tetrahydro-2-thioxo-5H-
imidazo[4,5-c]quinolin-4(9bH)-one (3d). Compound was prepared
from 1c in 98% yield. Colourless crystals, mp 207–213 ꢁC (ethyl
acetate), IR: 3420, 3138, 3061, 2983, 2911, 1687, 1598, 1494, 1468,
1404, 1257, 1219, 1142, 1091, 1070, 1056, 949, 895, 809, 765, 753,
CCDC-734258 and 734259 for 4l and 4k, respectively, contain
the supplementary crystallographic data for this paper. These data
can be obtained free of charge via http://www.ccdc.cam.ac.uk/
data_request/cif.
698, 657, 645, 596, 577, 529 cmꢀ1
. Anal. Calcd (found) for
4.2. Preparation of 3-amino-1H,3H-quinoline-2,4-diones (1)
C22H17N3O2S: C 68.20 (68.02); H 4.42 (4.52); N 10.85 (10.71). Pos-
itive-ion APCI-MS: m/z 388 [MþH]þ (100%), 356 [MþH–S]þ, 253
[MþH–C6H5NCS]þ; positive-ion APCI-MS/MS of m/z 388: 253
[MþH–C6H5NCS]þ (100%), 236 [MþH–C6H5NHCSNH2]þ, 208
[MþH–C6H5NHCSNH2–CO]þ. Negative-ion APCI-MS: m/z 386
Starting 3-substituted 3-amino-1H,3H-quinoline-2,4-diones (1)
were prepared from corresponding 3-chloro derivatives according
to the protocol described.5

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Z. Pruckova et al. / Tetrahedron 65 (2009) 9103–9115
9109
[MꢀH]ꢀ (100%); negative-ion APCI-MS/MS of m/z 386: 352 [MꢀH–
H2S]ꢀ, 267 [MꢀH–C6H5–NCO]ꢀ, 251 [MꢀH–C6H5NCS]ꢀ.
(ethyl acetate), IR: 3371, 3175, 3127, 2958, 2932, 2862, 1672, 1600,
1491, 1467, 1431, 1410, 1393, 1373, 1336, 1284, 1216, 1183, 1159,
1125, 1084, 1040, 1026, 1000, 973, 908, 856, 774, 758, 739, 690, 669,
650, 575, 528 cmꢀ1. Anal. Calcd (found) for C19H27N3O2S: C 63.13
(63.28); H 7.53 (7.42); N 11.62 (11.49). Positive-ion APCI-MS: m/z
362 [MþH]þ (18%), 344 [MþH–H2O]þ (100%), 350 [MþH–S]þ;
positive-ion APCI-MS/MS of m/z 362: 289 [MþH–CH3NCS]þ
(100%). Negative-ion APCI-MS: m/z 360 [MꢀH]ꢀ (100%), 331
[MꢀH–CH3N]ꢀ; negative-ion APCI-MS/MS of m/z 360: 316 [MꢀH–
C3H8]ꢀ, 287 [MꢀH–CH3NCS]ꢀ (100%), 241 [MꢀH–CH3NCS–H2O–
CO]ꢀ.
4.3.5. 3a-Butyl-1,3-dimethyl-9b-hydroxy-1,2,3,3a-tetrahydro-2-thi-
oxo-5H-imidazo[4,5-c]quinolin-4(9bH)-one (3e). Compound was pre-
pared from 1e in 82% yield. Colourless crystals, mp 235–239 ꢁC (ethyl
acetate), IR: 3291, 3197, 3136, 3069, 2959, 2930, 2871, 1676, 1618,
1600, 1496, 1467, 1441, 1393, 1365, 1335, 1309, 1291, 1250, 1206, 1183,
1156, 1116, 1079, 1041, 1016, 1002, 969, 952, 909, 845, 759, 730, 693,
672, 648, 612, 566, 535, 510 cmꢀ1
. Anal. Calcd (found) for
C16H21N3O2S: C 60.16 (60.02); H 6.63 (6.78); N 13.16 (13.08). Positive-
ion APCI-MS: m/z 320 [MþH]þ (9%), 302 [MþH–H2O]þ (100%), 288
[MþH–S]þ; positive-ion APCI-MS/MS of m/z 320: 247 [MþH–
CH3NCS]þ (100%), 229 [MþH–CH3NCS–H2O]þ, 201 [MþH–CH3NCS–
H2O–CO]þ. Negative-ion APCI-MS: m/z 318 [MꢀH]ꢀ (100%), 289
[MꢀH–CH3N]ꢀ; negative-ion APCI-MS/MS of m/z 318: 274 [MꢀH–
C3H8]ꢀ, 245 [MꢀH–CH3NCS]ꢀ (100%).
4.3.10. 3,3a-Dibutyl-9b-hydroxy-1-phenyl-1,2,3,3a-tetrahydro-2-thi-
oxo-5H-imidazo[4,5-c]quinolin-4(9bH)-one (3j). Compound was pre-
pared from 1i in 96% yield. Colourless crystals, mp 234–238 ꢁC (ethyl
acetate), IR: 3330, 3062, 2958, 2932, 2861, 1665, 1600, 1497, 1466,
1459, 1444, 1414, 1387, 1379, 1336, 1286, 1226, 1187, 1155, 1125, 1043,
1021, 1002, 995, 913, 754, 747, 695, 672, 648, 579, 528 cmꢀ1. Anal.
Calcd (found) for C24H29N3O2S: C 68.05 (67.89); H 6.90 (7.02); N 9.92
(9.78). Positive-ion APCI-MS: m/z 424 [MþH]þ, 406 [MþH–H2O]þ
(100%), 392 [MþH–S]þ, 380 [MþH–C3H8]þ; positive-ion APCI-MS/
MS of m/z 424: 305 [MþH–C6H5–NCO]þ, 289 [MþH–C6H5NCS]þ
(100%), 271 [MþH–C6H5NCS–H2O]þ. Negative-ion APCI-MS: m/z 422
[M–H]ꢀ (100%), 393, 287 [MꢀH–C6H5NCS]ꢀ.
4.3.6. 3a-Butyl-9b-hydroxy-3-methyl-1-phenyl-1,2,3,3a-tetrahydro-
2-thioxo-5H-imidazo[4,5-c]quinolin-4(9bH)-one (3f). Compound was
prepared from 1e in 97% yield. Colourless crystals, mp 258–263 ꢁC
(ethanol), IR: 3275, 3199, 3061, 2927, 2881, 1668, 1600, 1498, 1454,
1403, 1387, 1365, 1321, 1307, 1209, 1199, 1184, 1158, 1129, 1111, 1087,
1042, 1022, 1009, 987, 962, 945, 915, 838, 805, 756, 722, 698, 674,
645, 578, 523 cmꢀ1. Anal. Calcd (found) for C21H23N3O2S: C 66.12
(66.23); H 6.08 (6.23); N 11.01 (10.92). Positive-ion APCI-MS: m/z
382 [MþH]þ (100%), 364 [MþH–H2O]þ; positive-ion APCI-MS/MS of
m/z 382: 263 [MþH–C6H5–NCO]þ, 247 [MþH–C6H5NCS]þ (100%),
228 [MþH–C3H8–C6H5–SH]þ. Negative-ion APCI-MS: m/z 380
[MꢀH]ꢀ (100%); negative-ion APCI-MS/MS of m/z 380: 261 [MꢀH–
C6H5–NCO]ꢀ, 245 [MꢀH–C6H5NCS]ꢀ (100%).
4.3.11. 3-Butyl-9b-hydroxy-1-methyl-3a-phenyl-1,2,3,3a-tetrahydro-
2-thioxo-5H-imidazo[4,5-c]quinolin-4(9bH)-one (3k). Compound was
prepared from 1k in 74% yield. Colourless crystals, mp 227–230 ꢁC
(benzene), IR: 3343, 3131, 3072, 2958, 2931, 2873, 1677, 1618, 1599,
1493, 1460, 1429, 1399, 1375, 1277, 1229, 1214, 1179, 1155, 1130, 1099,
1054, 1031, 973, 896, 858, 776, 754, 707, 678, 661, 558 cmꢀ1. Anal.
Calcd (found) for C21H23N3O2S: C 66.12 (66.22); H 6.08 (6.22); N 11.01
(10.93). Positive-ion APCI-MS: m/z 382 [MþH]þ (32%), 364 [MþH–
H2O]þ (100%), 350 [MþH–S]þ, 338 [MþH–C3H8]þ; positive-ion APCI-
MS/MS of m/z 382: 309 [MþH–CH3NCS]þ (100%), 291 [MþH–
C6H5CH2]þ, 263 [MþH–C6H5–NCO]þ. Negative-ion APCI-MS: m/z 380
[MꢀH]ꢀ (100%), 351 [MꢀCH3N]ꢀ; negative-ion APCI-MS/MS of m/z
380: 362 [MꢀH–H2O]ꢀ, 336 [MꢀH–C3H8]ꢀ, 307 [MꢀH–CH3NCS]ꢀ,
289 [MꢀH–C6H5CH2]ꢀ, 261 [MꢀH–C6H5–NCO]ꢀ (100%), 247 [MꢀH–
C4H9NCS–H2O]ꢀ.
4.3.7. 1,3-Dimethyl-9b-hydroxy-3a-phenyl-1,2,3,3a-tetrahydro-2-
thioxo-5H-imidazo[4,5-c]quinolin-4(9bH)-one (3g). Compound was
prepared from 1g in 77% yield. Colourless crystals, mp 246–250 ꢁC
(benzene), IR: 3377, 3219, 3073, 2972, 2936, 1703, 1616, 1597, 1488,
1464, 1446, 1372, 1304, 1234, 1212, 1152, 1126, 1093, 1050, 1031,
1018, 974, 960, 945, 892, 872, 852, 743, 703, 659, 645, 613, 585, 562,
539 cmꢀ1. Anal. Calcd (found) for C18H17N3O2S: C 63.70 (63.57); H
5.05 (5.12); N 12.38 (12.21). Positive-ion APCI-MS: m/z 340 [MþH]þ
(47%), 322 [MþH–H2O]þ (100%), 308 [MþH–S]þ; positive-ion APCI-
MS/MS of m/z 340: 267 [MþH–CH3NCS]þ (100%), 249 [MþH–
CH3NCS–H2O]þ, 236, 221 [MþH–C6H5–NCO]þ. Negative-ion
APCI-MS: m/z 338 [MꢀH]ꢀ (100%), 309 [MꢀH–CH3N]ꢀ; negative-
ion APCI-MS/MS of m/z 338: 320 [MꢀH–H2O]ꢀ, 294, 265 [MꢀH–
CH3NCS]ꢀ, 247 [MꢀH–CH3NCS–H2O]ꢀ (100%), 219 [MꢀH–C6H5–
NCO]ꢀ.
4.3.12. 3-Butyl-1,3a-diphenyl-9b-hydroxy-1,2,3,3a-tetrahydro-2-thi-
oxo-5H-imidazo[4,5-c]quinolin-4(9bH)-one (3l). Compound was pre-
pared from 1k in 60% yield. Colourless crystals, mp 251–254 ꢁC
(ethyl acetate), IR: 3372, 3129, 3069, 2959, 2932, 2871, 1673, 1600,
1494, 1457, 1397, 1368, 1285, 1224, 1145, 1132, 1100, 1055, 1046, 1027,
976, 951, 898, 836, 747, 695, 675, 581, 529 cmꢀ1. Anal. Calcd (found)
for C26H25N3O2S: C 70.40 (70.27); H 5.68 (5.75); N 9.47 (9.39). Pos-
itive-ion APCI-MS: m/z 444 [MþH]þ (100%), 309 [MþH–C6H5NCS]þ;
positive-ion APCI-MS/MS of m/z 444: 325 [MþH–C6H5–NCO]þ, 309
[MþH–C6H5NCS]þ (100%). Negative-ion APCI-MS: m/z 442 [MꢀH]ꢀ
(100%), 307 [MꢀH–C6H5NCS]ꢀ; negative-ion APCI-MS/MS of m/z
442: 424 [MꢀH–H2O]ꢀ, 398 [MꢀH–CS]ꢀ, 323 [MꢀH–C6H5–NCO]ꢀ,
307 [MꢀH–C6H5NCS]ꢀ (100%).
4.3.8. 1,3a-Diphenyl-9b-hydroxy-3-methyl-1,2,3,3a-tetrahydro-2-
thioxo-5H-imidazo[4,5-c]quinolin-4(9bH)-one (3h). Compound was
prepared from 1g in 93% yield. Colourless crystals, mp 248–252 ꢁC
(benzene), IR: 3401, 3063, 3035, 2976, 2912, 1673, 1617, 1601, 1494,
1445, 1385, 1360, 1305, 1217, 1191, 1148, 1126, 1096, 1046, 1025,
1003, 976, 949, 912, 896, 836, 804, 748, 697, 682, 662, 584, 572,
529 cmꢀ1. Anal. Calcd (found) for C23H19N3O2S: C 68.81 (68.75); H
4.77 (4.90); N 10.47 (10.32). Positive-ion APCI-MS: m/z 402 [MþH]þ
(75%), 384 [MþH–H2O]þ, 370 [MþH–S]þ (100%); positive-ion APCI-
MS/MS of m/z 402: 283 [MþH–C6H5–NCO]þ, 267 [MþH–C6H5NCS]þ
(100%), 249 [MþH–C6H5NCS–H2O]þ, 236. Negative-ion APCI-MS:
m/z 400 [MꢀH]ꢀ (100%), 265 [MꢀH–C6H5NCS]ꢀ; negative-ion
APCI-MS/MS of m/z 400: 382 [MꢀH–H2O]ꢀ, 281 [MꢀH–C6H5–
NCO]ꢀ, 265 [MꢀH–C6H5NCS]ꢀ (100%), 247 [MꢀH–C6H5NCS–H2O]ꢀ.
4.3.13. 3-Benzyl-3a-butyl-9b-hydroxy-1-methyl-1,2,3,3a-tetrahydro-2-
thioxo-5H-imidazo[4,5-c]quinolin-4(9bH)-one (3m). Compound was
prepared from 1m in 74% yield. Colourless crystals, mp 216–224 ꢁC
(benzene), IR: 3305, 3203, 3162, 2955, 2930, 2859, 1691, 1615, 1601,
1494, 1453, 1415, 1395, 1352, 1334, 1293, 1284, 1246, 1176, 1153, 1128,
1107, 1070, 1049, 1001, 976, 942, 753, 714, 665, 632, 581, 563,
527 cmꢀ1. Anal. Calcd (found) for C22H25N3O2S: C 66.81 (66.70); H
6.37 (6.52); N 10.62 (10.49). Positive-ion APCI-MS: m/z 396 [MþH]þ
(19%), 378 [MþH–H2O]þ (100%), 364 [MþH–S]þ; positive-ion APCI-
MS/MS of m/z 396: 365, 323 [MþH–CH3NCS]þ (100%), 303 [MþH–
C6H5NH2]þ, 277 [MþH–C6H5–NCO]þ, 272 [MþH–C6H5CH2–SH]þ, 241,
4.3.9. 3,3a-Dibutyl-9b-hydroxy-1-methyl-1,2,3,3a-tetrahydro-2-thi-
oxo-5H-imidazo[4,5-c]quinolin-4(9bH)-one (3i). Compound was
prepared from 1i in 83% yield. Colourless crystals, mp 217–223 ꢁC

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9110
215,164. Negative-ion APCI-MS: m/z 394 [MꢀH]ꢀ (100%), 365 [MꢀH–
CH3N]ꢀ; negative-ion APCI-MS/MS of m/z 394: 350 [MꢀH–C3H8]ꢀ,
337 [MꢀH–C4H9]ꢀ, 321 [MꢀH–CH3NCS]ꢀ (100%), 303 [MꢀH–
C6H5CH2]ꢀ, 275 [MꢀH–C6H5–NCO]ꢀ.
mixture was evaporated to dryness in vacuo. The residue was
dissolved in pyridine (3 mL) and solution was evaporated to
dryness. The residue was washed with water and crystallized
from appropriate solvent or separated by column chromatogra-
phy on silica gel.
4.3.14. 3-Benzyl-3a-butyl-9b-hydroxy-1-phenyl-1,2,3,3a-tetrahydro-
2-thioxo-5H-imidazo[4,5-c]quinolin-4(9bH)-one (3n). Compound was
prepared from 1m in 96% yield. Colourless crystals, mp 219–222 ꢁC
(benzene), IR: 3354, 3185, 3130, 3065, 2959, 2928, 2870, 1666, 1600,
1496, 1445, 1409, 1385, 1368, 1320, 1293, 1243, 1181, 1156, 1125, 1085,
Method C. The reaction was carried out in the same manner as in
Method A, however, a mixture of acetic acid and absolute ethanol
(9:1) was used as the reaction medium.
4.4.1. 4-(2-Aminophenyl)-5-butyl-3-methyl-1H-imidazole-2(3H)-
thione (4a). Compound was prepared from 3a in respective yields
22% (Method A) or 60% (Method B). Colourless crystals, mp 211–
212 ꢁC (benzene), IR: 3404, 3321, 3079, 2953, 2928, 2871, 2740,
1628, 1571, 1506, 1457, 1391, 1307, 1239, 1156, 1135, 1034, 1012, 935,
855, 788, 743, 681, 635, 600, 534, 518 cmꢀ1. Anal. Calcd (found) for
C14H19N3S: C 64.33 (64.65); H 7.33 (7.45); N 16.08 (15.81). Positive-
ion APCI-MS: m/z 262 [MþH]þ (100%), 230 [MþH–S]þ; positive-ion
APCI-MS/MS of m/z 262: 245 [MþH–NH3]þ, 232, 219 [MþH–
C3H7]þ, 206 [MþH–C4H8]þ, 172 [MþH–C4H9–SH]þ (100%). Nega-
tive-ion APCI-MS: m/z 340 [2ꢂ(MꢀH)–H-2ꢂC4H9–SH–S]ꢀ, 260
[MꢀH]ꢀ (100%); negative-ion APCI-MS/MS of m/z 260: 245 [MꢀH–
CH3]ꢀ, 226 [MꢀH–H2S]ꢀ, 211 [MꢀH–H2S–CH3]ꢀ (100%), 201
[MꢀH–NHCS]ꢀ, 186 [MꢀH–H2O–C4H8]ꢀ, 170 [MꢀH–H2O–C4H9–
SH]ꢀ.
1074,1037,1023, 997, 951, 914, 753, 719, 698, 670, 648, 573, 528 cmꢀ1
.
Anal. Calcd (found) for C27H27N3O2S: C 70.87 (70.77); H 5.95 (6.12); N
9.18 (9.09). Positive-ion APCI-MS: m/z 458 [MþH]þ, 440 [MþH–
H2O]þ, 426 [MþH–S]þ, 414 [MþH–C3H8]þ (100%); positive-ion APCI-
MS/MS of m/z 458: 365 [MþH–C6H5NH2]þ, 339 [MþH–C6H5–NCO]þ,
323 [MþH–C6H5NCS]þ (100%). Negative-ion APCI-MS: m/z 456
[MꢀH]ꢀ (100%), 427, 321 [MꢀH–C6H5NCS]ꢀ; negative-ion APCI-MS/
MS of m/z 456: 337 [MꢀH–C6H5–NCO]ꢀ, 321 [MꢀH–C6H5NCS]ꢀ
(100%), 303 [MꢀH–C6H5NCS–H2O]ꢀ.
4.3.15. 3-Benzyl-9b-hydroxy-1-methyl-3a-phenyl-1,2,3,3a-tetrahydro-
2-thioxo-5H-imidazo[4,5-c]quinolin-4(9bH)-one (3o). Compound was
prepared from 1o in 76% yield. Colourless crystals, mp 230–235 ꢁC
(ethyl acetate–hexane), IR: 3402, 3156, 3061, 2983, 2917, 1698, 1680,
1615, 1598, 1556, 1493, 1438, 1384, 1341, 1327, 1297, 1262, 1240, 1172,
1136, 1105, 1068, 1052, 1040, 1021, 993, 958, 895, 861, 761, 751, 724,
708, 666, 656, 633, 589, 564, 549 cmꢀ1. Anal. Calcd (found) for
C24H21N3O2S: C 69.37 (69.23); H 5.09 (5.23); N 10.11 (9.97). Positive-
ion APCI-MS: m/z 416 [MþH]þ, 398 [MþH–H2O]þ (100%), 384
[MþH–S]þ, 343 [MþH–CH3NCS]þ; positive-ion APCI-MS/MS of m/z
416: 343 [MþH–CH3NCS]þ (100%), 325 [MþH–C6H5CH2]þ, 297
[MþH–C6H5–NCO]þ, 236 [MþH–C6H5CH2NHCSNHCH3]þ. Negative-
ion APCI-MS: m/z 414 [MꢀH]ꢀ (100%), 385 [MꢀH–CH3N]ꢀ; nega-
tive-ion APCI-MS/MS of m/z 414: 396 [MꢀH–H2O]ꢀ, 370, 341
[MꢀH–CH3NCS]ꢀ (100%), 323 [MꢀH–C6H5CH2]ꢀ, 295 [MꢀH–C6H5–
NCO]ꢀ.
4.4.2. 4-(2-Aminophenyl)-5-butyl-3-phenyl-1H-imidazole-2(3H)-
thione (4b). Compound was prepared from 3b in 49% yields
(Method B). Yellow crystals, mp 258–265 ꢁC (ethanol), IR: 3419,
3287, 3184, 3063, 2924, 2872, 2709, 1648, 1618, 1597, 1577, 1498,
1453, 1389, 1372, 1309, 1234, 1159, 1145, 1074, 1032, 934, 854, 839,
792, 770, 749, 699, 653, 624, 542, 515, 503 cmꢀ1. Anal. Calcd (found)
for C19H21N3S: C 70.55 (70.45); H 6.54 (6.65); N 12.99 (12.81).
Positive-ion APCI-MS: m/z 324 [MþH]þ (100%), 292 [MþH–S]þ;
positive-ion APCI-MS/MS of m/z 324: 307 [MþH–NH3]þ, 294
[MþH–CH2NH2]þ, 281 [MþH–C3H7]þ, 265 [MþH–NHCS]þ, 231
[MþH–C6H5–NH2]þ, 189
[MþH–C6H5NCS]þ, 172
[MþH–
C6H5NHCS–NH2]þ, 130 [MþH–C6H5NCS–NH2–C3H7]þ (100%). Neg-
ative-ion APCI-MS: m/z 322 [MꢀH]ꢀ (100%); negative-ion APCI-MS/
MS of m/z 322: 292 [MꢀH–CH2NH2]ꢀ, 265 [MꢀH–C4H9]ꢀ, 239
[MꢀH–C4H9CN]ꢀ (100%).
4.3.16. 3-Benzyl-1,3a-diphenyl-9b-hydroxy-1,2,3,3a-tetrahydro-2-
thioxo-5H-imidazo[4,5-c]quinolin-4(9bH)-one (3p). Compound was
prepared from 1o in 88% yield. Colourless crystals, mp 257–263 ꢁC
(ethyl acetate), IR: 3350, 3061, 3028, 2984, 2905, 1674, 1615, 1597,
1493, 1451, 1434, 1367, 1340, 1301, 1268, 1235,1170, 1152, 1138, 1103,
1089, 1071, 1050, 1024, 969, 945, 915, 896, 810, 766, 749, 720, 709,
694, 661, 640, 584, 560, 530, 516 cmꢀ1. Anal. Calcd (found) for
C29H23N3O2S: C 72.93 (73.12); H 4.85 (4.91); N 8.80 (8.76). Positive-
ion APCI-MS: m/z 478 [MþH]þ (100%), 460 [MþH–H2O]þ, 446
[MþH–S]þ; positive-ion APCI-MS/MS of m/z 478: 359 [MþH–C6H5–
NCO]þ, 343 [MþH–C6H5NCS]þ (100%). Negative-ion APCI-MS: m/z
476 [MꢀH]ꢀ (100%), 341 [MꢀH–C6H5NCS]ꢀ; negative-ion APCI-MS/
MS of m/z 476: 458 [MꢀH–H2O]ꢀ, 377, 341 [MꢀH–C6H5NCS]ꢀ
(100%).
4.4.3. 4-(2-Aminophenyl)-3-methyl-5-phenyl-1H-imidazole-2(3H)-
thione (4c). Compound was prepared from 3c in yields 7% (Method
A) or 69% yield (Method B). Colourless crystals, mp 310–315 ꢁC
(ethanol), IR: 3476, 3401, 3312, 3080, 2938, 2751, 1625, 1574, 1491,
1455, 1430, 1388, 1301, 1274, 1256, 1228, 1134, 1113, 1074, 1021, 962,
940, 918, 783, 770, 750, 697, 678, 614, 574, 546 cmꢀ1. Anal. Calcd
(found) for C16H15N3S: C 68.30 (68.15); H 5.37 (5.45); N 14.93
(14.80). Positive-ion APCI-MS: m/z 282 [MþH]þ (100%); positive-
ion APCI-MS/MS of m/z 282: 265 [MþH–NH3]þ (100%), 249
[MþH–SH]þ, 223 [MþH–NHCS]þ. Negative-ion APCI-MS: m/z 280
[MꢀH]ꢀ (100%); negative-ion APCI-MS/MS of m/z 280: 265 [MꢀH–
CH3]ꢀ (100%), 246 [MꢀH–H2S]ꢀ, 231 [MꢀH–H2S–CH3]ꢀ.
4.4. General methods for the molecular rearrangement
of compounds 3
4.4.4. 4-(2-Aminophenyl)-3,5-diphenyl-1H-imidazole-2(3H)-thione
(4d). Compound was prepared from 3d in 50% yield (Method B).
Colourless crystals, mp 327–335 ꢁC (DMF–methanol), IR: 3443,
3345, 3056, 2919, 2737, 1633, 1616, 1596, 1573, 1498, 1489, 1452,
1390, 1374, 1310, 1262, 1234, 1158, 1075, 1028, 1005, 967, 911, 788,
767, 759, 749, 725, 697, 637, 577, 552, 507 cmꢀ1. Anal. Calcd (found)
for C21H17N3S: C 73.44 (73.55); H 4.99 (5.15); N 12.23 (12.31).
Positive-ion APCI-MS: m/z 344 [MþH]þ (100%); positive-ion APCI-
MS/MS of m/z 344: 327 [MþH–NH3]þ, 224 [MþH–C6H5CNH–
NH2]þ, 209 [MþH–C6H5NCS]þ, 193 [MþH–C6H5NCS–NH2]þ (100%).
Negative-ion APCI-MS: m/z 342 [MꢀH]ꢀ (100%); negative-ion APCI-
MS/MS of m/z 342: 308 [MꢀH–H2S]ꢀ, 283 [MꢀH–NHCS]ꢀ, 265
Method A. The solution of starting compound 3 (1 mmol) in
acetic acid (8 mL) was heated to reflux for the time given in Table 2.
The course of the reaction was monitored by TLC. After cooling, the
reaction mixture was evaporated to dryness in vacuo and the res-
idue was crystallized from appropriate solvent or separated by
column chromatography on silica gel.
Method B. The solution of starting compound 3 (1 mmol) in
concd hydrochloric acid (5 mL) was heated to reflux for the time
given in Table 2. In same cases a small quantity of acetic acid was
added to dissolution of starting compound. The course of the
reaction was monitored by TLC. After cooling, the reaction

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Z. Pruckova et al. / Tetrahedron 65 (2009) 9103–9115
9111
[MꢀH–C6H5]ꢀ, 250 [MꢀH–C6H5NH]ꢀ, 239 [MꢀH–C5H5CN]ꢀ
N 13.23 (13.11). Positive-ion APCI-MS: m/z 318 [MþH]þ (100%), 286
[MþH–S]þ; positive-ion APCI-MS/MS of m/z 318: 284 [MþH–H2S]þ,
262 [MþH–C4H8]þ (100%). Negative-ion APCI-MS: m/z 316 [MꢀH]ꢀ
(100%); negative-ion APCI-MS/MS of m/z 316: 288, 259 [MꢀH–
C4H9]ꢀ, 201 [MꢀH–C4H9NCS]ꢀ, 186 [MꢀH–C4H9NCS–CH3]ꢀ.
(100%).
4.4.5. 4-(2-Aminophenyl)-5-butyl-1,3-dimethyl-1H-imidazole-
2(3H)-thione (4e). Compound was prepared from 3e in respective
yields 6% (Method A) and 43% (Method B). Colourless crystals, mp
108–111 ꢁC (cyclohexane), IR: 3406, 3314, 3202, 2958, 2928, 2859,
1624, 1573, 1494, 1454, 1391, 1310, 1260, 1214, 1177, 1127, 1094, 1017,
865, 755, 645, 514 cmꢀ1. Anal. Calcd (found) for C15H21N3S: C 65.41
(65.53); H 7.69 (7.78); N 15.26 (15.11). Positive-ion APCI-MS: m/z
276 [MþH]þ (100%); positive-ion APCI-MS/MS of m/z 276: 246
[MþH–2ꢂCH3]þ, 233 [MþH–C3H7]þ, 219 [MþH–C4H9]þ, 206
[MþH–CH3–C4H7]þ (100%), 203 [MþH–CH3NCS]þ, 172. Negative-
ion APCI-MS: m/z 274 [MꢀH]ꢀ (100%); negative-ion APCI-MS/MS of
m/z 575: 274 [MꢀH]ꢀ (100%); negative-ion APCI-MS/MS of m/z 274:
219 [MꢀH–C3H7]ꢀ, 201 [MꢀH–CH3NCS]ꢀ, 186 [MꢀH–C3H8–CS]ꢀ.
4.4.10. 4-(2-Aminophenyl)-1,5-dibutyl-3-phenyl-1H-imidazole-
2(3H)-thione (4j). Compound was prepared from 3j in respective
yields 5% (Method A) and 52% (Method B). Colourless crystals, mp
155–156 ꢁC (benzene–hexane), IR: 3310, 3181, 3046, 2954, 2928,
2868, 1616, 1599, 1574, 1499, 1465, 1454, 1432, 1404, 1394, 1378,
1356, 1312, 1292, 1265, 1158, 1121, 1173, 1127, 950, 778, 752, 736,
724, 692, 644, 547, 522 cmꢀ1. Anal. Calcd (found) for C23H29N3S: C
72.78 (72.65); H 7.70 (7.86); N 11.07 (11.21). Positive-ion APCI-MS:
m/z 380 [MþH]þ (100%), 348 [MþH–S]þ; positive-ion APCI-MS/MS
of m/z 380: 346 [MþH–H2S]þ, 324 [MþH–C4H8]þ (100%), 265
[MþH–C4H9NCS]þ, 245 [MþH–C6H5NCS]þ, 208 [MþH–C4H9NCS–
C4H9]þ, 172.
4.4.6. 4-(2-Aminophenyl)-5-butyl-1-methyl-3-phenyl-1H-imidazole-
2(3H)-thione (4f). Compound was prepared from 3f in 28% (Method
A) and 76% yields (Method B). Yellowish crystals, mp 179–182 ꢁC
(benzene–hexane), IR: 3300, 3189, 2954, 2930, 2872, 1621, 1596,
1573, 1493, 1455, 1387, 1357, 1310, 1242, 1110, 1027, 791, 754, 743,
695, 648, 545 cmꢀ1. Anal. Calcd (found) for C20H23N3S: C 71.18
(71.25); H 6.87 (6.95); N 12.45 (12.62). Positive-ion APCI-MS: m/z
338 [MþH]þ (100%); positive-ion APCI-MS/MS of m/z 338: 295
[MþH–C3H7]þ, 281 [MþH–C4H9]þ, 265 [MþH–CH3NCS]þ (88%),
233, 206 [MþH–C4H7–C6H5]þ (100%), 172 [MþH–C4H7–C6H5–
H2S]þ, 146, 130 [MþH–C3H8–C6H5NCSNCH3]þ. Negative-ion APCI-
MS: m/z 336 [MꢀH]ꢀ (100%); negative-ion APCI-MS/MS of m/z 336:
263 [MꢀH–CH3NCS]ꢀ (100%).
4.4.11. 4-(2-Aminophenyl)-1-butyl-3-methyl-5-phenyl-1H-imidaz-
ole-2(3H)-thione (4k). Compound was prepared from 3k in re-
spective yields 25% (Method A) and 55% yield (Method B).
Colourless crystals, mp 147–149 ꢁC (benzene–hexane), IR: 3405,
3378, 3298, 3202, 3043, 2958, 2929, 2873, 2854, 1620, 1594, 1576,
1490, 1457, 1448, 1408, 1383, 1310, 1258, 1209, 1140, 1114, 1074,
1049, 1021, 934, 861, 814, 762, 748, 700, 641, 573, 535 cmꢀ1. Anal.
Calcd (found) for C20H23N3S: C 71.18 (71.02); H 6.87 (6.99); N 12.45
(12.61). Positive-ion APCI-MS: m/z 338 [MþH]þ (100%), 306
[MþH–S]þ; positive-ion APCI-MS/MS of m/z 338: 304 [MþH–
H2S]þ, 282 [MþH–C4H8]þ (100%), 265 [MþH–CH3NCS]þ, 223
[MþH–C4H9NCS]þ, 193 [MþH–C4H9NCS–CH3]þ. Negative-ion
APCI-MS: m/z 336 [MꢀH]ꢀ (100%); negative-ion APCI-MS/MS of
m/z 336: 263 [MꢀH–CH3NCS]ꢀ, 221 [MꢀH–C4H9NCS]ꢀ (100%), 206
[MꢀH–C4H9NCS–CH3]ꢀ.
4.4.7. 4-(2-Aminophenyl)-1,3-dimethyl-5-phenyl-1H-imidazole-
2(3H)-thione (4g). Compound was prepared from 3g in yields 41%
(Method A) and 76% (Method B). Colourless crystals, mp 203–205 ꢁC
(benzene–hexane); IR: 3393, 3303, 3197, 3048, 2942, 1623, 1573,
1489, 1449, 1388, 1310, 1266, 1200, 1131, 1075, 1051, 1023, 1014, 946,
921, 856, 822, 767, 749, 726, 697, 678, 647, 526 cmꢀ1. Anal. Calcd
(found) for C17H17N3S: C 69.12 (69.03); H 5.80 (5.95); N 14.22
(14.08). Positive-ion APCI-MS: m/z 296 [MþH]þ (100%), 264 [MþH–
S]þ; positive-ion APCI-MS/MS of m/z 296: 279 [MþH–NH3]þ, 265,
223 [MþH–CH3NCS]þ (100%), 208 [MþH–CH3NCS–CH3]þ, 193
[MþH–CH3NHCSNCH3]þ, 182. Negative-ion APCI-MS: m/z 294
[MꢀH]ꢀ (100%); negative-ion APCI-MS/MS of m/z 294: 221 [MꢀH–
CH3NCS]ꢀ (100%), 206 [Mꢀ2H–CH3NCS–CH3]ꢀ.
4.4.12. 4-(2-Aminophenyl)-3,5-diphenyl-1-butyl-1H-imidazole-
2(3H)-thione (4l). Compound was prepared from 3l in respective
yields 18% (Method A) and 50% (Method B). Colourless crystals, mp
147–149 ꢁC (benzene–hexane), IR: 3407, 3279, 3183, 3056, 2961,
2929, 2871, 1618, 1596, 1575, 1557, 1494, 1454, 1401, 1370, 1306,
1291, 1264,1239, 1156, 1133, 1076, 1025, 935, 851, 760, 748, 695, 661,
586, 542, 513 cmꢀ1. Anal. Calcd (found) for C25H25N3S: C 75.15
(75.02); H 6.31 (6.45); N 10.52 (10.41). Positive-ion APCI-MS: m/z
400 [MþH]þ (100%), 368 [MþH–S]þ; positive-ion APCI-MS/MS of
m/z 400: 366 [MþH–H2S]þ, 344 [MþH–C4H8]þ (100%), 285 [MþH–
C4H9NCS]þ. Negative-ion APCI-MS: m/z 398 [MꢀH]ꢀ (100%); neg-
ative-ion APCI-MS/MS of m/z 398: 342 [MꢀH–C4H8]ꢀ (100%), 283
[MꢀH–C4H9NCS]ꢀ.
4.4.8. 4-(2-Aminophenyl)-3,5-diphenyl-1-methyl-1H-imidazole-
2(3H)-thione (4h). Compound was prepared from 3h in respective
yields 2% (Method A) or 76% (Method B). Colourless crystals, mp
297–301 ꢁC (benzene), IR: 3371, 3331, 3203, 3052, 2924, 1619,
1596, 1575, 1498, 1453, 1424, 1383, 1355, 1308, 1235, 1155, 1108,
4.4.13. 4-(2-Aminophenyl)-1-benzyl-5-butyl-3-methyl-1H-imidazole-
2(3H)-thione (4m). Compound was prepared from 3m in respective
yields 12% (Method A) and 86% (Method B). Colourless crystals, mp
132–133 ꢁC (cyclohexane), IR: 3430, 3312, 3224, 3197, 2957, 2925,
2871,1620,1569,1492,1455,1399,1388,1360,1345,1307,1256,1194,
1091, 1079, 1018, 963, 754, 738, 704, 530 cmꢀ1. Anal. Calcd (found)
for C21H25N3S: C 71.75 (71.69); H 7.17 (7.25); N 11.95 (11.79). Posi-
tive-ion APCI-MS: m/z 352 [MþH]þ (100%); positive-ion APCI-MS/
MS of m/z 352: 318 [MþH–H2S]þ, 309 [MþH–C3H7]þ, 261 [MþH–
C6H5CH2]þ (100%), 232 [MþH–C6H5CH2–CH3N]þ, 219, 201 [MþH–
NHCS–C6H5CH3]þ, 186 [MþH–C6H5CH2NCS–NH3]þ. Negative-ion
APCI-MS: m/z 350 [MꢀH]ꢀ (100%); negative-ion APCI-MS/MS of m/z
350: 201 [MꢀH–C6H5CH2NCS]ꢀ (100%), 186 [MꢀH–C6H5CH2NCS–
CH3]ꢀ, 170 [MꢀH–C6H5CH2NHCSNHCH3]ꢀ.
1023, 807, 790, 761, 747, 728, 705, 693, 659, 578, 544, 510 cmꢀ1
.
Anal. Calcd (found) for C22H19N3S: C 73.92 (73.81); H 5.36 (5.51);
N 11.75 (11.64). Positive-ion APCI-MS: m/z 358 [MþH]þ (100%);
positive-ion APCI-MS/MS of m/z 358: 285 [MþH–CH3NCS]þ, 223
[MþH–C6H5NCS]þ, 208 [MþH–C6H5NCSNH]þ, 193 [MþH–
C6H5NCSNHCH3]þ (100%); negative-ion APCI-MS: m/z 356
[MꢀH]ꢀ (100%).
4.4.9. 4-(2-Aminophenyl)-1,5-dibutyl-3-methyl-1H-imidazole-
2(3H)-thione (4i). Compound was prepared from 3i in respective
yields 28% (Method A) or 56% (Method B). Colourless crystals, mp
106–109 ꢁC (benzene–hexane), IR: 3353, 3301, 3235, 3205, 3069,
3031, 2955, 2929, 2858, 1633, 1596, 1569, 1493, 1459, 1442, 1408,
1391, 1357, 1312, 1287, 1263, 1204, 1174, 1157, 1139, 1127, 1085, 1043,
1018, 950, 931, 887, 849, 820, 750, 740, 681, 638, 613, 543 cmꢀ1
Anal. Calcd (found) for C18H27N3S: C 68.09 (68.15); H 8.57 (8.76);
.
4.4.14. 4-(2-Aminophenyl)-1-benzyl-5-butyl-3-phenyl-1H-imidazole-
2(3H)-thione (4n). Compound was prepared from 3n in respective

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yields 17% (Method A) and 53% (Method B). Colourless crystals, mp
150–153 ꢁC (benzene–hexane), IR: 3405, 3315, 3218, 3064, 3028,
2957, 2928, 2869, 1618, 1598, 1574, 1497, 1453, 1427, 1403, 1393,
1370, 1349, 1310, 1288, 1260, 1224, 1160, 1139, 1074, 1027, 957, 836,
751, 725, 700, 687, 649, 630, 589, 542, 525 cmꢀ1. Anal. Calcd (found)
for C26H27N3S: C 75.51 (75.40); H 6.58 (6.71); N 10.16 (10.27). Pos-
itive-ion APCI-MS: m/z 414 [MþH]þ (100%), 382 [MþH–S]þ; posi-
tive-ion APCI-MS/MS of m/z 414: 323 [MþH–C6H5CH2]þ (100%), 294
[MþH–C6H5–C3H7]þ, 281, 263 [MþH–C6H5NCS–NH2]þ. Negative-
ion APCI-MS: m/z 412 [MꢀH]ꢀ (100%); negative-ion APCI-MS/MS of
m/z 412: 321 [MꢀH–C6H5CH2]ꢀ (100%), 292 [MꢀH–C6H5–C3H7]ꢀ,
263 [MꢀH–C6H5CH2NCS]ꢀ.
[Fþ26þ2H]ꢀ, 280 [Fꢀ2H]ꢀ; negative-ion APCI-MS/MS of m/z 587:
306 [Fþ26þ2H]ꢀ (100%), 280 [FꢀH]ꢀ.
4.4.19. 1,3-Bis(2-(2,3-dihydro-1,3-dimethyl-4-butyl-2-thioxo-1H-
imidazol-5-yl)phenyl)urea (6e). Compound was prepared from 3e
in 25% yield (Method A). Colourless crystals, mp 213–217 ꢁC (cy-
clohexane), IR: 3256, 2954, 2928, 2870, 1703, 1580, 1524, 1453,
1393, 1291, 1258, 1219, 1187, 1135, 1048, 1022, 950, 851, 781, 761,
668, 626, 517 cmꢀ1. Anal. Calcd (found) for C31H40N6OS2: C 64.55
(64.47); H 6.99 (7.06); N 14.57 (14.71). Positive-ion APCI-MS: m/z
577 [MþH]þ (100%), 545 [MþH–S]þ; positive-ion APCI-MS/MS of
m/z 577: 316 [Fþ26þN]þ (100%), 302 [Fþ26]þ, 276 [F]þ, 259
[FꢀNH3]þ. Negative-ion APCI-MS: m/z 575 [MꢀH]ꢀ (100%); nega-
tive-ion APCI-MS/MS of m/z 575: 274 [Fꢀ2H]ꢀ (100%).
4.4.15. 4-(2-Aminophenyl)-1-benzyl-3-methyl-5-phenyl-1H-imidazole-
2(3H)-thione (4o). Compound was prepared from 3o in respective
yields 21% (Method A) or 69% (Method B). Colourless crystals, mp 180–
182 ꢁC (benzene–hexane), IR: 3393, 3308, 3209, 3060, 3031, 2940,
1621, 1573, 1588, 1446, 1436, 1402, 1383, 1357, 1309, 1260, 1206, 1158,
1108, 1075, 1048, 1022, 967, 923, 825, 765, 753, 699, 640, 591,
535 cmꢀ1. Anal. Calcd (found) for C23H21N3S: C 74.36 (74.48); H 5.70
(5.81); N 11.31 (11.22). Positive-ion APCI-MS: m/z 372 [MþH]þ (100%),
340 [MþH–S]þ; positive-ion APCI-MS/MS of m/z 372: 355 [MþH–
NH3]þ, 338 [MþH–H2S]þ, 313 [MþH–NHCS]þ, 281 [MþH–C6H5CH2]þ
(100%), 264 [MþH–C6H5CH2–NH3]þ, 221 [MþH–C6H5NCS–NH2]þ.
Negative-ion APCI-MS: m/z 370 [MꢀH]ꢀ (100%)þnegative-ion APCI-
MS/MS of m/z 370: 297 [MꢀH–CH3NCS]ꢀ, 279 [MꢀH–C6H5CH2]ꢀ, 221
[MꢀH–C6H5CH2NCS]ꢀ (100%), 206 [MꢀH–C6H5CH2–CH3NCS]ꢀ.
4.4.20. 1,3-Bis(2-(4-butyl-2,3-dihydro-3-methyl-1-phenyl-2-thioxo-
1H-imidazol-5-yl)phenyl)urea (6f). Compound was prepared from
3f in 41% yield (Method A). Colourless crystals, mp 221–223 ꢁC
(cyclohexane), IR: 3318, 3065, 2956, 2929, 2861, 1706, 1598, 1580,
1518, 1501, 1449, 1391, 1363, 1287, 1256, 1190, 1111, 1073, 1028, 987,
831, 756, 694, 647, 537 cmꢀ1. Anal. Calcd (found) for C41H44N6OS2: C
70.25 (70.41); H 6.33 (6.41); N 11.99 (12.08). Positive-ion APCI-MS:
m/z 701 [MþH]þ (100%), 364 [Fþ26]þ; positive-ion APCI-MS/MS of
m/z 701: 655 [MþH–CSH2]þ, 378 [Fþ26þN]þ, 364 [Fþ26]þ (100%),
338 [F]þ. Negative-ion APCI-MS: m/z 699 [MꢀH]ꢀ (100%); negative-
ion APCI-MS/MS of m/z 699: 336 [Fꢀ2H]ꢀ (100%).
4.4.21. 1,3-Bis(2-(2,3-dihydro-1,3-dimethyl-4-phenyl-2-thioxo-1H-
imidazol-5-yl)phenyl)urea (6g). Compound was prepared from 3g
in 24% yield (Method A). Colourless crystals, mp 298–301 ꢁC (ben-
zene), IR: 3440, 3262, 3058, 3030, 2926,1710,1604,1578,1521,1451,
1390, 1288, 1262, 1228, 1179, 1142, 1075, 1047, 1023, 918, 856, 762,
699, 666, 645, 527 cmꢀ1. Anal. Calcd (found) for C35H32N6OS2: C
68.15 (68.23); H 5.23 (5.32); N 13.63 (13.58). Positive-ion APCI-MS:
m/z 617 [MþH]þ (100%); positive-ion APCI-MS/MS of m/z 617: 336
(100%) [Fþ26þN]þ, 322 [Fþ26]þ, 296 [F]þ. Negative-ion APCI-MS:
m/z 615 [MꢀH]ꢀ (100%); negative-ion APCI-MS/MS of m/z 412: 294
(100%) [Fꢀ2H]ꢀ, 221[Fꢀ2H–CH3NCS]ꢀ, 206.
4.4.16. 4-(2-Aminophenyl)-1-benzyl-3,5-diphenyl-1H-imidazole-
2(3H)-thione (4p). Compound was prepared from 3p in respective
yields 7% (Method A) or 71% (Method B). Colourless crystals, mp
211–214 ꢁC (benzene–hexane), IR: 3443, 3327, 3059, 3032, 2917,
1614, 1575, 1556, 1538, 1495, 1453, 1428, 1401, 1368, 1308, 1266,
1177, 1158, 1103, 1076, 1028, 1002, 984, 959, 918, 850, 821, 789, 757,
728, 697, 657, 593, 576, 542, 512 cmꢀ1. Anal. Calcd (found) for
C28H23N3S: C 77.57 (77.41); H 5.35 (5.61); N 9.69 (9.51). Positive-ion
APCI-MS: m/z 434 [MþH]þ (100%), 402 [MþH–S]þ; positive-ion
APCI-MS/MS of m/z 434: 417 [MþH–NH3]þ, 400 [MþH–H2S]þ, 375
[MþH–NHCS]þ, 356 [MþH–C6H6]þ, 343 [MþH–C6H5CH2]þ (100%),
283 [MþH–C6H5NCS–NH2]þ. Negative-ion APCI-MS: m/z 432
[MꢀH]ꢀ (100%); negative-ion APCI-MS/MS of m/z 432: 341 [MꢀH–
C6H5CH2]ꢀ (100%).
4.4.22. 1,3-Bis(2-(2,3-dihydro-1,4-diphenyl-3-methyl-2-thioxo-1H-
imidazol-5-yl)phenyl)urea (6h). Compound was prepared from 3h
in 65% yield (Method A). Colourless crystals, mp 310–317 ꢁC (ben-
zene–hexane), IR: 3415, 3338, 3061, 2923, 1705, 1598, 1579, 1524,
1498, 1448, 1385, 1359, 1291, 1247, 1190, 1113, 1077, 1023, 926, 821,
756, 737, 695, 663, 576, 547, 509 cmꢀ1. Anal. Calcd (found) for
C45H36N6OS2: C 72.95 (72.80); H 4.90 (5.16); N 11.34 (11.22). Pos-
itive-ion APCI-MS: m/z 741 [MþH]þ (100%), 384 [Fþ26]þ, 358 [F]þ;
positive-ion APCI-MS/MS of m/z 741: 695, 398, 384 [Fþ26]þ
(100%), 358 [F]þ. Negative-ion APCI-MS: m/z 739 [MꢀH]ꢀ (100%),
409, 385, 371; negative-ion APCI-MS/MS of m/z 739: 356 [Fꢀ2H]ꢀ
(100%).
4.4.17. 1,3-Bis(2-(4-butyl-2,3-dihydro-1-methyl-2-thioxo-1H-imidazol-
5-yl)phenyl)urea (6a). Compound was prepared from 3a in 29% yield
(Method A). Colourless crystals, mp 140–148 ꢁC (benzene–hexane),
IR: 3275, 3170, 3106, 2956, 2930, 2871, 1709, 1579, 1525, 1501, 1449,
1388, 1290, 1248, 1192, 1135, 1035, 757, 612, 533 cmꢀ1. Anal. Calcd
(found) for C29H36N6OS2: C 63.47 (63.29); H 6.61 (6.75); N 15.31
(15.43). Positive-ion APCI-MS: m/z 549 [MþH]þ (100%), 517 [MþH–
S]þ, 262 [F]þ (100%); positive-ion APCI-MS/MS of m/z 549: 515
[MþH–H2S]þ, 302 [Fþ26þN]þ (100%), 288 [Fþ26]þ, 262 [F]þ. Nega-
tive-ion APCI-MS: m/z 547 [MꢀH]ꢀ (100%); negative-ion APCI-MS/
MS of m/z 547: 286 [Fþ26–2H]ꢀ (100%).
4.4.23. 1,3-Bis(2-(3,4-dibutyl-1-methyl-2-thioxo-2,3-dihydro-1H-
imidazol-5-yl)phenyl)urea (6i). Compound was prepared from 3i in
23% yield (Method A). Colourless crystals, mp 183–188 ꢁC (cyclo-
hexane), IR: 3278, 3027, 3109, 3029, 2958, 2932, 2872, 1706, 1579,
1523,1484,1451,1408,1385,1289,1248,1227,1188,1143,1114,1089,
1025, 950, 878, 765, 685, 628, 539 cmꢀ1. Anal. Calcd (found) for
C37H52N6OS2: C 67.23 (67.45); H 7.93 (7.85); N 12.71 (12.58). Posi-
tive-ion APCI-MS: m/z 661.4 [MþH]þ (100%); positive-ion APCI-MS/
MS of m/z 661: 358 [Fþ26þN]þ (100%), 344 [Fþ26]þ, 318 [F]þ.
Negative-ion APCI-MS: m/z 659 [MꢀH]ꢀ (100%); negative-ion APCI-
MS/MS of m/z 659: 316 [Fꢀ2H]ꢀ (100%).
4.4.18. 1,3-Bis(2-(2,3-dihydro-1-methyl-4-phenyl-2-thioxo-1H-imid-
azol-5-yl)phenyl)urea (6c). Compound was prepared from 3c in
33% yield (Method A). Yellowish crystals, mp 305–316 ꢁC (ethanol),
IR: 3406, 3060, 2940, 2758,1707,1649,1580, 1525, 1490, 1449,1384,
1318,1291,1236, 1192, 1132, 1075,1026, 962, 912, 787, 763, 694, 612,
562 cmꢀ1. Anal. Calcd (found) for C33H28N6OS2: C 67.32 (67.45); H
4.79 (4.85); N 14.27 (14.15). Positive-ion APCI-MS: m/z 589 [MþH]þ
(100%), 557 [MþH–S]þ, 452, 420, 380, 354, 321, 308 [Fþ26]þ, 282
[F]þ; positive-ion APCI-MS/MS of m/z 589: 322 [Fþ26þN]þ (100%),
308 [Fþ26]þ, 296 [FþN]þ, 282 [F]þ. Negative-ion APCI-MS: m/z 587
[MꢀH]ꢀ (100%), 450, 442, 410, 352, 338, 322 [Fþ26þN–2H]ꢀ, 306
4.4.24. 1,3-Bis(2-(3,4-dibutyl-2,3-dihydro-1-phenyl-2-thioxo-1H-
imidazol-5-yl)phenyl)urea (6j). Compound was prepared from 3j

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9113
(Method A) in 15% yield. Colourless crystals, mp 198–201 ꢁC (cy-
clohexane), IR: 3457, 3309, 3068, 2958, 2931, 2871, 1706, 1638,
1598, 1580, 1523, 1500, 1449, 1405, 1372, 1286, 1247, 1222, 1187,
1132, 1112,1075, 1027, 1004, 946, 836, 756, 694, 631, 541 cmꢀ1. Anal.
Calcd (found) for C47H56N6OS2: C 71.90 (71.77); H 7.19 (7.26); N
10.70 (10.63). Positive-ion APCI-MS: m/z 785.4 [MþH]þ (40%), 753
[MþH–S]þ, 406 [Fþ26]þ, 380 [F]þ (100%); positive-ion APCI-MS/MS
of m/z 785: 729 [MþH–C4H8]þ, 697 [MþH–2ꢂC3H8]þ, 462, 406
[Fþ26]þ (100%), 380 [F]þ, 374 [Fþ26–S]þ, 350 [Fþ26–C4H8]þ.
Negative-ion APCI-MS: m/z 783.5 [MꢀH]ꢀ (100%); negative-ion
APCI-MS/MS of m/z 783: 378 [Fꢀ2H]ꢀ (100%).
MS: m/z 851 [MꢀH]ꢀ (100%), 427; negative-ion APCI-MS/MS of m/z
851: 412 [Fꢀ2H]ꢀ, 412 [Fꢀ2H–C6H5CH2]ꢀ.
4.4.29. 1,3-Bis(2-(3-benzyl-2,3-dihydro-1-methyl-4-phenyl-2-thi-
oxo-1H-imidazol-5-yl)phenyl)urea (6o). Compound was prepared
from 3o in 45% (Method A). Colourless crystals, mp 252–257 ꢁC
(benzene–hexane), IR: 3395, 3277, 3060, 3030, 2925, 2851, 1710,
1605, 1579, 1523, 1497, 1449, 1402, 1384, 1290, 1228, 1203, 1108,
1077, 1049, 1025, 968, 922, 859, 763, 738, 700, 640, 589, 549 cmꢀ1
.
Anal. Calcd (found) for C47H40N6OS2: C 73.41 (73.27); H 5.24 (5.39);
N 10.93 (10.78). Positive-ion APCI-MS: m/z 769 [MþH]þ (100%), 737
[MþH–O]þ, 398 [Fþ26]þ, 372 [F]þ, 340; positive-ion APCI-MS/MS of
m/z 769: 678 [MþH–C6H5CH2]þ, 645, 587 [MþH–2ꢂC6H5CH2]þ,
474, 448, 412 [Fþ26þN]þ (100%), 398 [Fþ26]þ, 372 [F]þ. Negative-
ion APCI-MS: m/z 767 [MꢀH]ꢀ (100%), 412, 398, 385; negative-ion
APCI-MS/MS of m/z 767: 370 [FꢀH]ꢀ (100%).
4.4.25. 1,3-Bis(2-(3-butyl-2,3-dihydro-1-methyl-4-phenyl-2-thioxo-
1H-imidazol-5-yl)phenyl)urea (6k). Compound was prepared from
3k in 26% yield (Method A). Colourless crystals, mp 247–251 ꢁC
(ethyl acetate), IR: 3281, 3057, 2958, 2932, 2871, 1713, 1605, 1579,
1524, 1450, 1407, 1383, 1289, 1229, 1206, 1185, 1145, 1113, 1075,
1050, 1025, 858, 762, 702, 640, 562 cmꢀ1. Anal. Calcd (found) for
C41H44N6OS2: C 70.25 (70.39); H 6.33 (6.51); N 11.99 (11.82). Posi-
tive-ion APCI-MS: m/z 701 [MþH]þ (100%), 669 [MþH–S]þ; posi-
tive-ion APCI-MS/MS of m/z 701: 378 [Fþ26þN]þ (100%), 364
[Fþ26]þ, 338 [F]þ, 330 [Fþ26–H2S]þ, 322. Negative-ion APCI-MS:
m/z 699 [MꢀH]ꢀ (100%); negative-ion APCI-MS/MS of m/z 699: 336
[Fꢀ2H]ꢀ (100%).
4.4.30. 1,3-Bis(2-(2,3-dihydro-1,4-diphenyl-3-benzyl-2-thioxo-1H-
imidazol-5-yl)phenyl)urea (6p). Compound was prepared from 3p
in yield 37% (Method A). Colourless crystals, mp 262–265 ꢁC (ben-
zene–hexane), IR: 3409, 3359, 3060, 3032, 2925, 2853, 1711, 1597,
1580, 1519,1496, 1449, 1397, 1366, 1287, 1264,1231, 1187, 1077, 1027,
960, 921, 839, 791, 760, 699, 655, 595, 574, 548, 513 cmꢀ1. Anal.
Calcd (found) for C57H44N6OS2: C 76.65 (76.47); H 4.97 (5.09); N
9.41 (9.30). Positive-ion APCI-MS: m/z 893 [MþH]þ (86%), 861
[MþH–S]þ, 460 [Fþ26]þ (68%), 434 [F]þ (100%), 402; positive-ion
APCI-MS/MS of m/z 893: 802 [MþH–C6H5CH2]þ, 769, 711 [MþH–
2ꢂC6H5CH2]þ (100%), 680, 460 [Fþ26]þ, 434 [F]þ, 368, 343. Nega-
tive-ion APCI-MS: m/z 891 [MꢀH]ꢀ (100%), 474, 447, 432 [Fꢀ2H]ꢀ;
negative-ion APCI-MS/MS of m/z 891: 432 [Fꢀ2H]ꢀ (100%), 341.
4.4.26. 1,3-Bis(2-(1,4-diphenyl-3-butyl-2-thioxo-2,3-dihydro-1H-
imidazol-5-yl)phenyl)urea (6l). Compound was prepared from 3l
in 40% yield (Method A). Colourless crystals, mp 253–260 ꢁC
(benzene–hexane), IR: 3407, 3059, 2958, 2932, 2871, 1709, 1597,
1579, 1518, 1497, 1448, 1401, 1364, 1289, 1240, 1188, 1133, 1076,
1025, 945, 830, 755, 696, 656, 582 cmꢀ1. Anal. Calcd (found) for
C51H48N6OS2: C 74.24 (74.15); H 5.86 (6.02); N 10.19 (10.06).
Positive-ion APCI-MS: m/z 825 [MþH]þ (100%), 793 [MþH–S]þ,
426 [Fþ26]þ, 400 [F]þ (100%); positive-ion APCI-MS/MS of m/z
825: 791 [MþH–H2S]þ, 770, 737 [MþH–C3H8]þ, 482
[Fþ26þC4H8]þ, 456, 426 [Fþ26]þ (100%), 400 [F]þ. Negative-ion
APCI-MS: m/z 823 [MꢀH]ꢀ (100%); negative-ion APCI-MS/MS of
m/z 823: 398 [Fꢀ2H]ꢀ (100%).
4.4.31. N(2-(5-Butyl-2,3-dihydro-3-methyl-2-thioxo-1H-imidazol-4-
yl)phenyl)acetamide (7a). Compound was prepared from 3a in
yield 3% (Method A). Yellow crystals, mp 92–102 ꢁC (hexane), IR:
3110, 2955, 2930, 2872, 1670, 1602, 1581, 1524, 1496, 1450, 1386,
1298, 1241, 1135, 1036, 1014, 929, 762, 680, 656, 601, 550, 531 cmꢀ1
.
Anal. Calcd (found) for C16H21N3OS: C 63.33 (63.55); H 6.98 (7.25);
N 13.85 (13.71). Positive-ion APCI-MS: m/z 304 [MþH]þ (100%);
positive-ion APCI-MS/MS of m/z 304: 262 [MþH–NCO]þ (100%),
274. Negative-ion APCI-MS: m/z 302 [MꢀH]ꢀ (100%), 288; negative-
ion APCI-MS/MS of m/z 302: 260 [MꢀH–NCO]ꢀ (100%).
4.4.27. 1,3-Bis(2-(3-benzyl-4-butyl-2,3-dihydro-1-methyl-2-thioxo-
1H-imidazol-5-yl)phenyl)urea (6m). Compound was prepared
from 3m (Method A) in 17% yield. Colourless crystals, mp 144–
150 ꢁC (hexane), IR: 3459, 3292, 2955, 2929, 2869, 1708, 1579,
1519, 1453, 1402, 1391, 1357, 1289, 1193, 1091, 1026, 761, 731,
4.4.32. N(2-(5-Butyl-2,3-dihydro-1-methyl-3-phenyl-2-thioxo-1H-
imidazol-4-yl)phenyl)acetamide (7f). Compound was prepared
from 3f in 6% yield (Method A). Beige crystals, mp 180–187 ꢁC (cy-
clohexane), IR: 3328, 3059, 2952, 2930, 2869, 1668, 1580, 1520,
1501, 1469, 1448, 1382, 1353, 1297, 1252, 1105, 1071, 767, 757, 695,
591, 536 cmꢀ1. Anal. Calcd (found) for C22H25N3OS: C 69.62 (69.55);
H 6.64 (6.85); N (11.07, 11.21). Positive-ion APCI-MS: m/z 380
[MþH]þ (100%), 348 [MþH–S]þ; positive-ion APCI-MS/MS of m/z
380: 338 [MþH–NCO]þ (100%). Negative-ion APCI-MS: m/z 378
[MꢀH]ꢀ (100%); negative-ion APCI-MS/MS of m/z 378: 360 [MꢀH–
H2O]ꢀ, 336 [MꢀH–NCO]ꢀ, 305 [MꢀH–CH3NCS]ꢀ (100%), 263
[MꢀH–C4H9NCS]ꢀ.
701 cmꢀ1
. Anal. Calcd (found) for C43H48N6OS2: C 70.84
(70.81); H 6.64 (6.81); N 11.53 (11.50). Positive-ion APCI-MS:
m/z 729 [MþH]þ (75%), 697 [MþH–S]þ, 656 [MþH–CH3NCS]þ,
432, 378 [Fþ26]þ, 352 [F]þ (100%), 346 [Fþ26–S]þ, 320
[FꢀS]þ; positive-ion APCI-MS/MS of m/z 729: 638 [MþH–
C6H5CH2]þ,
605
[MþH–C6H5CH2–SH]þ,
547
[MþH–
2ꢂC6H5CH2]þ, 428 [MþH–NH2CSNH2]þ, 392 [Fþ26þN]þ
(100%), 378 [Fþ26]þ, 352 [F]þ. Negative-ion APCI-MS: m/z 727
[MꢀH]ꢀ (100%), 365; negative-ion APCI-MS/MS of m/z 727:
350 [Fꢀ2H]ꢀ (100%).
4.4.28. 1,3-Bis(2-(3-benzyl-4-butyl-2,3-dihydro-1-phenyl-2-thioxo-
1H-imidazol-5-yl)phenyl)urea (6n). Compound was prepared from
3n (Method A) in 20% yield. Colourless crystals, mp 138–144 ꢁC
(benzene), IR: 3316, 3062, 3032, 2956, 2929, 2869, 1706, 1580, 1519,
1499, 1450, 1401, 1369, 1286, 1227, 1191, 1075, 1029, 959, 757, 701,
541 cmꢀ1. Anal. Calcd (found) for C53H52N6OS2: C 74.61 (74.65); H
6.14 (6.23); N 9.85 (9.72). Positive-ion APCI-MS: m/z 853 [MþH]þ
(11%), 440 [Fþ26]þ, 414 [F]þ (100%), 408 [Fþ26–S]þ, 382 [FꢀS]þ;
positive-ion APCI-MS/MS of m/z 853: 762 [MþH–C6H5CH2]þ, 729
[MþH–C6H5CH2–SH]þ, 671 [MþH–2ꢂC6H5CH2]þ (100%), 530, 440
[Fþ26]þ, 414 [F]þ, 349, 278 [MþH–C6H5NCSH]þ. Negative-ion APCI-
4.4.33. N(2-(2,3-Dihydro-1,3-dimethyl-5-phenyl-2-thioxo-1H-imid-
azol-4-yl)phenyl)acetamide (7g). Compound was prepared from
3g in 10% yield (Method A). Colourless crystals, mp 248–249 ꢁC
(ethyl acetate–hexane), IR: 3362, 3050, 2983, 2946, 1686, 1605,
1581, 1521, 1474, 1445, 1387, 1301, 1243, 1206, 1185, 1139, 1073,
1049, 1027, 924, 859, 766, 747, 706, 673, 634, 583, 536 cmꢀ1. Anal.
Calcd (found) for C19H19N3OS: C 67.63 (67.75); H 5.86 (5.95); N
12.45 (12.62). Positive-ion APCI-MS: m/z 338 [MþH]þ (100%);
positive-ion APCI-MS/MS of m/z 338: 296 [MþH–C2H2O]þ (100%).
Negative-ion APCI-MS: m/z 336 [MꢀH]ꢀ (100%); negative-ion
APCI-MS/MS of m/z 336: 318 [MꢀH–H2O]ꢀ, 294 [MꢀH–C2H2O]ꢀ,

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245 [MꢀH–C6H5CH2]ꢀ, 221 [MꢀH–CH3NCS–C2H2O]ꢀ (100%), 206
[MꢀH–CH3NCS–C2H2O–CH3]ꢀ.
[MþH–CO]þ, 308 [MþH–H2O–CO]þ (100%), 282. Negative-ion
APCI-MS: m/z 352 [MꢀH]ꢀ (100%), 306 [MꢀH–H2O–CO]ꢀ; nega-
tive-ion APCI-MS/MS of m/z 352: 308 [MꢀH–C3H8]ꢀ, 306 [MꢀH–
H2O–CO]ꢀ (100%).
4.4.34. N(2-(2,3-Dihydro-3,5-diphenyl-1-methyl-2-thioxo-1H-imid-
azol-4-yl)phenyl)acetamide (7h). Compound was prepared from
3h in 4% yield (Method A). Colourless crystals, mp 252–257 ꢁC
(benzene–hexane), IR: 3356, 3257, 3051, 2923, 1693, 1678, 1660,
1598, 1579, 1524, 1499, 1449, 1382, 1357, 1298, 1257, 1158, 1113,
1075, 1023, 925, 820, 791, 758, 737, 696, 576, 550, 533 cmꢀ1. Anal.
Calcd (found) for C24H21N3OS: C 72.15 (69.98); H 5.30 (5.48); N
10.52 (10.43). Positive-ion APCI-MS: m/z 400 [MþH]þ (100%);
positive-ion APCI-MS/MS of m/z 400: 384 [MþH–O]þ, 358 [MþH–
NCO]þ (100%). Negative-ion APCI-MS: m/z 398 [MꢀH]ꢀ (100%);
negative-ion APCI-MS/MS of m/z 398: 356 [MꢀH–NCO]ꢀ, 325
[MꢀH–CH3NCS]ꢀ (100%), 282 [MꢀH–CH3NCS–NHCO]ꢀ.
4.4.39. Ethyl 2-(1-butyl-2,3-dihydro-3-methyl-5-phenyl-2-thioxo-1H-
imidazol-4-yl)phenylcarbamate (8k). Compound was prepared from
3k in 58% yield (Method C). Colourless crystals, mp 94–100 ꢁC
(hexane), IR: 3291, 2953, 2927, 2868, 1714, 1696, 1581, 1525, 1499,
1455, 1404, 1381, 1296, 1229, 1143, 1115, 1095, 1068, 1048, 1024, 947,
861, 844, 767, 728, 704, 638, 558, 504 cmꢀ1. Anal. Calcd (found) for
C23H27N3O2S: C 67.45 (67.37); H 6.65 (6.81); N 10.26 (10.32). Posi-
tive-ion APCI-MS: m/z 410 [MþH]þ (100%), 364 [MþH–CO–H2O]þ,
338 [MþH–COOC2H4]þ; positive-ion APCI-MS/MS of m/z 410: 382
[MþH–CO]þ, 364 [MþH–CO–H2O]þ (100%), 338 [MþH–COOC2H4]þ.
Negative-ion APCI-MS: m/z 408 [MꢀH]ꢀ (100%); negative-ion APCI-
MS/MS of m/z 408: 362 [MꢀH–CO–H2O]ꢀ (100%).
4.4.35. N(2-(1-Butyl-2,3-dihydro-3,5-diphenyl-2-thioxo-1H-imida-
zol-4-yl)phenyl)acetamide (7l). Compound was prepared from 3l in
4% yield (Method A). Colourless crystals, mp 239–242 ꢁC, IR: 3258,
3050, 2958, 2932, 2871, 1692, 1675, 1659, 1598, 1579, 1524, 1499,
1448, 1402, 1369, 1300, 1260, 1241, 1134, 1074, 1026, 948, 827, 789,
4.4.40. [2-(1-Butyl-3,5-diphenyl-2-thioxo-2,3-dihydro-1H-imidazo-
4-yl)-phenyl]-carbamic acid ethyl ester (8l). Compound was
prepared from 3l in 24% yield (Method A). Colourless crystals, mp
151–153 ꢁC (benzene–hexane), IR: 3346, 3061, 2960, 2932, 2872,
1733,1698,1585,1518,1497,1450,1401,1362,1300,1224,1208,1171,
1134, 1096, 1059, 1026, 926, 838, 820, 785, 761, 751, 695, 655, 630,
581, 541, 521 cmꢀ1. Anal. Calcd (found) for C28H29N3O2S: C 71.31
(71.43); H 6.20 (6.33); N 8.91 (8.78). Positive-ion APCI-MS: m/z 472
[MþH]þ (100%), 440 [MþH–S]þ, 426 [MþH–H2O–CO]þ; positive-
ion APCI-MS/MS of m/z 472: 444 [MþH–CO]þ, 438 [MþH–H2S]þ,
426 [MþH–H2O–CO]þ, 400, 370. Negative-ion APCI-MS: m/z 470
[MꢀH]ꢀ (100%); negative-ion APCI-MS/MS of m/z 470: 424 [MꢀH–
H2O–CO]ꢀ (100%), 398, 309 [MꢀH–C6H5NCO–NCO]ꢀ.
757, 695, 655, 581, 550, 535 cmꢀ1
. Anal. Calcd (found) for
C27H27N3OS: C 73.44 (73.23); H 6.16 (6.24); N 9.52 (9.49). Positive-
ion APCI-MS: m/z 442 [MþH]þ (100%); positive-ion APCI-MS/MS of
m/z 442: 400 [MþH–C2H2O]þ (100%), 386 [MþH–C4H8]þ, 344
[MþH–C2H2O–C4H8]þ. Negative-ion APCI-MS: m/z 440 [MꢀH]ꢀ
(100%); negative-ion APCI-MS/MS of m/z 440: 398 [MꢀH–C2H2O]ꢀ
(100%), 384 [MꢀH–C4H8]ꢀ, 375, 325 [MꢀH–C4H9NCS]ꢀ.
4.4.36. N(2-(1-Benzyl-5-butyl-2,3-dihydro-3-phenyl-2-thioxo-1H-
imidazol-4-yl)phenyl)acetamide (7n). Compound was prepared
from 3n (Method A) in 8% yield. Colourless crystals, mp 166–171 ꢁC
(ethyl acetate–hexane), IR: 3288, 2953, 2930, 2867, 1678, 1658,
1599, 1578, 1518,1501,1478,1450,1401, 1368,1351, 1297,1270,1252,
1196, 1162, 1109, 1075, 1030, 964, 848, 758, 724, 700, 641, 604, 557,
536 cmꢀ1. Anal. Calcd (found) for C28H29N3OS: C 73.81 (73.75); H
6.42 (6.53); N 9.22 (9.17). Positive-ion APCI-MS: m/z 456 [MþH]þ
(100%), 424 [MþH–S]þ; positive-ion APCI-MS/MS of m/z 456: 414
[MþH–NCO]þ, 365 [MþH–C6H5CH2]þ, 336 [MþH–C6H5CH2–
CH3N]þ, 323 [MþH–C6H5CH2–NCO]þ, 294. Negative-ion APCI-MS:
m/z 454 [MꢀH]ꢀ (100%); negative-ion APCI-MS/MS of m/z 454: 412
[MꢀH–NCO]ꢀ, 321 [MꢀH–C6H5CH2–NCO]ꢀ, 305 [MꢀH–
C6H5CH2NCS]ꢀ (100%), 263 [MꢀH–C6H5CH2NCS–NCO]ꢀ.
4.5. General procedures for acylation of compounds 4
4.5.1. Acetylation. To the solution of compound 4 (0.2 mmol) in
pyridine (1 mL), acetic anhydride (1 mL) was added at rt. After 24 h,
the solution was evaporated to dryness and the residue was
recrystallized. The following compounds, identical in all respects to
those prepared from 3 by Method A, were obtained: 7g (yield 63%),
7h (yield 80%), 7l (yield 83%) and 7n (yield 72%).
4.5.2. Ethoxycarbonylation. To the solution of compound
4
(0.2 mmol) in pyridine (1 mL), ethyl chloroformate (0.3 mL,
0.315 mmol) was added at rt. After 4 h, the solution was evaporated
to dryness and the residue was crystallized from benzene–hexane.
The following compounds, identical in all respects to those pre-
pared from 3 by Method C, were obtained: 8c (yield 53%), 8l (yield
58%).
4.4.37. N(2-(1-Benzyl-2,3-dihydro-3-methyl-5-phenyl-2-thioxo-1H-
imidazol-4-yl)phenyl)acetamide (7o). Compound was prepared
from 3o in 1% yield (Method A). Colourless crystals, mp 96–105 ꢁC
(benzene–hexane), IR: 3415, 3330, 3060, 3031, 2946, 2930, 1691,
1605, 1581, 1521, 1496, 1477, 1447, 1402, 1383, 1299, 1249, 1209,
1158, 1110, 1076, 1025, 967, 923, 864, 765, 736, 701, 681, 642, 587,
553, 544 cmꢀ1. Anal. Calcd (found) for C25H23N3OS: C 72.61 (72.73);
H 5.61 (5.72); N 10.16 (10.23). Positive-ion APCI-MS: m/z 414
[MþH]þ (100%); positive-ion APCI-MS/MS of m/z 414: 372 [MþH–
NCO]þ (100%), 323 [MþH–C6H5CH2]þ. Negative-ion APCI-MS: m/z
412 [MꢀH]ꢀ (100%); negative-ion APCI-MS/MS of m/z 412: 321
[MꢀH–C6H5CH2]ꢀ (100%), 278 [MꢀH–C6H5CH2NHCO]ꢀ.
Acknowledgements
This study was supported by the Ministry of Education, Youth
and Sports of the Czech Republic (Grant No. MSM 7088352101) and
the Czech Science Foundation (Grant No. 203/07/0320). The au-
ꢀ
´
thors thank Mrs. H. Gerzova (Faculty of Technology, Tomas Bata
´
University in Zlın) for technical help.
4.4.38. Ethyl 2-(2,3-dihydro-3-methyl-5-phenyl-2-thioxo-1H-imid-
azol-4-yl)phenylcarbamate (8c). Compound was prepared from 3c
in 74% yield (Method C). Colourless crystals, mp 232–238 ꢁC (ethyl
acetate–hexane), IR: 3274, 3102, 2975, 2940, 1720, 1698, 1637, 1580,
1528, 1493, 1475, 1455, 1379, 1338, 1294, 1283, 1240, 1170, 1135,
1094, 1065, 1047, 1024, 963, 916, 881, 835, 787, 771, 744, 699, 679,
615, 559, 533 cmꢀ1. Anal. Calcd (found) for C19H19N3O2S: C 64.57
(64.65); H 5.42 (5.51); N 11.89 (11.76). Positive-ion APCI-MS: m/z
354 [MþH]þ (100%), 322; positive-ion APCI-MS/MS of m/z 354: 326
Supplementary data
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2009.09.048.
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