Reaction of 3-phenyl-3-aminoquinoline-2,4-diones with isothiocyanates. Facile access to novel spiro-linked 2-thioxoimidazolidine-oxindoles and imidazoline-2-thiones

Article abstract of DOI:10.1016/j.tet.2010.01.041

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

Full text of DOI:10.1016/j.tet.2010.01.041

Tetrahedron 66 (2010) 2015–2025
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Reaction of 3-phenyl-3-aminoquinoline-2,4-diones with isothiocyanates.
Facile access to novel spiro-linked 2-thioxoimidazolidine-oxindoles
and imidazoline-2-thiones
a,
b,
c
d,
c
e
*
ꢀ
ˇ
´
´
´
ˇ
ˇ´
ˇ
˚
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 Institute of Physiology of the 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, Studentska 573, 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:
3-Phenyl-3-amino-1H,3H-quinoline-2,4-diones (1) react with alkyl or aryl isothiocyanates to give novel
9b-hydroxy-3a-phenyl-1,2,3,3a-tetrahydro-2-thioxo-5H-imidazo[4,5-c]quinolin-4(9bH)-ones in high
yields. These compounds rearrange in boiling acetic acid or concentrated hydrochloric acid to give novel
5-phenyl-2-thioxospiro[4H-imidazol-4,30-[3H]indol]-20(10H,3H)-ones, 5-hydroxy-5-phenyl-2-thioxospiro
[imidazolidine-4,30-[3H]indol]-20-ones and (2-methylaminophenyl)-5-phenyl-1H-imidazole-2(3H)-thio-
nes. All compounds were characterized by their 1H, 13C, IR and MS data, and in some cases also by 15N
NMR data. The structures and compositions of four compounds were confirmed by single crystal X-ray
diffraction.
Received 2 October 2009
Received in revised form
26 November 2009
Accepted 11 January 2010
Available online 18 January 2010
Keywords:
a
-Aminoketones
Ó 2010 Elsevier Ltd. All rights reserved.
Rearrangement
Spiro-heterocycles
Thioxo group
Thiourea derivatives
1. Introduction
Previous work has demonstrated that adducts of 3-amino-
quinolinediones and isocyanates undergo rearrangements that largely
In our laboratory, much attention has been paid to the reactivity
of 3-alkyl/aryl-3-amino-1H,3H-quinoline-2,4-diones.1 The addition
of these compounds to isocyanic acid (from the decomposition of
urea or nitrourea) or isocyanates yields products that rearrange in
an acidic media to giveddepending on the character of the
substituentsdimidazoquinazolines, oxindoles, indolylureas, bis[2-
(imidazolyl)phenyl]ureas, imidazolones and spiro-linked imidazo-
lidine-oxindoles. These transformations, which were briefly
illustrated in our last paper on this topic,1 provide simple pre-
parative methods for new types of heterocyclic compounds.
The exceptional structural diversity obtained from the molecu-
lar rearrangement mentioned above prompted us to examine the
analogous addition of 3-aminoquinolinediones to isothiocyanates,
as well as the acid-catalyzed rearrangement of the resulting
products. We anticipated the formation of new sulfur-containing
heterocycles; such compounds are of interest since many bio-
logically active compounds belong to this structural class.2,3
depend on the substituents present at positions 1 and 3 of the starting
compounds.1 Consequently, we divided the starting 3-amino-
quinolinediones into three different groups.4 Compounds of the first
group, containing compounds substituted at position 1 with an alkyl
or aryl group and at position 3 with an alkyl group, react with alkyl or
aryl isothiocyanates to give cyclic adducts, which rearrange under
acidic conditions to (E)- and/or (Z)-4-butylidene-2-thioxo-1H0-spi-
ro[imidazoline-5,30-indole]-2,20-diones.4 In our last paper on this
subject we studied compounds of the second group, which lack
a substituent at position 1.5 These react with methyl and phenyl iso-
thiocyanates to yield analogous cyclic addition products; however,
these rearrange in acidic media to three different products: 4-(2-
aminophenyl)-1H-imidazole-2(3H)-thiones, 1,3-bis(2-(2,3-dihydro-
2-thioxo-1H-imidazol-5-yl)phenyl)ureas and (as minor products)
N-(2-(2,3-dihydro-2-thioxo-1H-imidazol-4-yl)phenyl)acetamides.
In this work, we demonstrate that the reaction of 3-amino-
quinolinediones of the third group, bearing an alkyl or aryl group in
position 1 and a phenyl group at position 3 (1), provides cyclic addition
product 3, which rearrange in an acidic medium to give novel
5-phenyl-2-thioxospiro[4H-imidazol-4,30-[3H]indol]-20(10H,3H)-ones
* Corresponding author. Tel.: þ420 576 031 413; fax: þ420 577 210 172.
´
E-mail address: klasek@ft.utb.cz (A. Klasek).
0040-4020/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.01.041

´
A. Klasek et al. / Tetrahedron 66 (2010) 2015–2025
2016
S
4, 5-hydroxy-5-phenyl-2-thioxospiro[imidazolidine-4,30-[3H]indol]-
20-ones
and (2-methylaminophenyl)-5-phenyl-1H-imidazole-
2(3H)-thiones 6.
R3
3´
S
1
C-NHR3
N
O
N
O
5
3
NHR2
1´
HO
9b
N
R2
R3NCS
CHCl3
6
R2
3a
4
Ph
O
3
Ph
O
3a-h
Ph
O
1
N
R1
and/or
N
R1
N
R1
2. Results and discussion
6
1
2d
Key of substituents:
Isothiocyanates were reacted with 3-amino-3-phenyl-
quinolinediones 1 by boiling the reaction components in chloro-
form (Scheme 1, Table 1). Methyl isothiocyanate and phenyl
isothiocyanate were chosen as model thiocyanates; methyl and
phenyl groups were similarly chosen as substituents for position 1.
The starting amines 1 (Scheme 1) were obtained from the corre-
sponding 3-chloro derivatives according to procedures described
elsewhere.6 One novel amine 1c was prepared.
a
b
c
d
e
f
g
h
R1 Me Me Ph Ph Me Me
Ph Ph
Bu Bu Bu Bu
R2
H
H
H
H
R3 Me Ph Me Ph Me Ph
Me Ph
Scheme 1.
In principle, 3-aminoquinolinediones may afford two different
adducts in the reaction with isothiocyanates: 3-thioureido-1H,3H-
quinoline-2,4-diones and/or cyclic 9b-hydroxy-1,2,3,3a-tetrahydro-
2-thioxo-5H-imidazo[4,5-c]quinolin-4(9bH)-ones. In the reaction of
3-aminoquinolinediones with isocyanates,1 both acyclic and cyclic
products were obtained. However, in previous work,4,5 the reaction
of 3-aminoquinolinediones with isothiocyanates was find to pro-
vide, with only one exception, the cyclic products. Our present
findings appear to confirm this trend; the selected 3-amino-3-
phenylquinoline-2,4-diones 1 react with isothiocyanates to give
only the cyclic isomers 3 in good toverygood yields (Scheme 1, Table
1). NMR spectra of compounds 3 are given in Table 2. Characteristic
hydroxyl proton signals appear in the 1H NMR spectra in the region
of 6.80–7.63 ppm. Additionally, 13C signals arising from the sp3 hy-
bridized carbon atoms at position 3a lie in the region of 72.0–
Table 1
Preparation of compounds 2 and 3 by the reaction of 3-aminoquinolinediones 1 with
isothiocyanates
Entry Starting compound Substituentsa
Time (h) Products (yield, %)
R1
R2
R3
1
2
3
4
5
6
7
8
1a
1a
1c
1c
1e
1e
1g
1g
Me
Me
Ph
H
H
H
H
Bu
Bu
Bu
Bu
Me
Ph
Me
Ph
Me
Ph
Me
Ph
3
3
3a (73)
3b (77)
3
3c (86)
Ph
2
4
2d (48), 3d (35)
3e (66)
Me
Me
Ph
10
1
3f (74)
3g (90)
Ph
2
3h (88)
a
R3 from isothiocyanate.
Table 2
1H and 13C chemical shifts (
d, ppm) of compounds 3a–h in DMSO-d6
Position
3a
3b
3c
3d
3e
3f
3g
3h
dH
dC
dH
dC
dH
dC
dH
dC
dH
dC
dH
dC
dH
dC
dH
dC
2
3a
4
5a
6
7
8
9
d
183.6
72.0
168.4
137.3
115.6
131.0
123.5
128.4
121.1
89.8
d
d
d
d
d
183.4
73.0
168.5
137.3
115.3
130.9
123.0
128.4
121.1
91.5
d
d
183.7
72.4
d
183.6
73.6
d
184.7
77.5
168.1
137.0
115.5
130.9
123.4
129.0
120.7
89.2
d
d
184.2
78.6
d
184.8
78.0
d
184.3
79.0
d
d
d
d
d
d
d
d
d
169.6
138.4
116.6
130.8
123.7
128.4
120.9
90.2
d
168.7
d
d
168.1
137.0
115.2
130.7
122.9
128.6
120.5
90.3
d
138.3
138.0
116.8
130.7
123.7
129.2
120.7
89.6
d
158.3
a
b
d
d
d
d
d
d
d
7.41
7.61
7.30
7.79
d
7.39
6.43
7.41
7.29
7.83
d
6.39
7.24
6.89
7.12
d
116.3
130.7
7.39
7.52
7.22
7.68
d
7.32
7.37
6.85
7.07
d
6.43
7.34
7.19
7.75
d
6.37
7.18
6.85
7.21
d
116.3
130.5
7.47
6.93
7.03
123.3
123.2
c
d
9a
9b
OH
d
120.8
91.9
d
120.3
90.6
d
d
d
d
d
d
d
d
d
6.80
d
7.35
d
6.92
d
d
7.42
d
7.02
d
7.40
d
d
7.20
d
d
7.63
d
10(3a)
20(3a)
30(3a)
40(3a)
10(R1)
20(R1)
30(R1)
40(R1)
10(R2)
133.9
126.7
128.2
128.2
30.0
d
133.8
126.8
128.1
128.4
30.2
d
133.6
126.7
128.4
128.4
137.5
128.9
130.3
128.8
d
133.5
131.6
128.8
128.1
128.1
30.0
d
131.7
131.3
128.9
128.4
128.9
137.6
130.3
128.9
128.9
48.0
131.4
e
f
g
h
c
7.24
7.31
7.31
3.46
d
7.34
7.26
7.35
7.36
d
126.8
7.31
7.39
7.39
3.51
d
7.56
7.47
7.43
d
e
e
c
f
f
g
g
h
h
c
7.27
7.34
3.55
c
a
c
c
c
c
b
d
d
d
d
3.59
d
30.1
d
d
h
d
7.27
7.64
7.57
9.97
7.39
7.68
7.62
10.28
7.40
7.67
7.58
3.72
3.22
2.32
1.61
1.23
1.13
0.83
2.93
d
d
d
d
d
d
d
d
d
7.74
7.63
3.81
3.31
2.41
1.71
1.26
1.16
0.86
d
d
d
d
d
d
d
d
9.89
d
10.22
d
d
d
d
3.77
3.30
2.35
1.62
1.27
1.17
0.86
2.80
d
48.0
3.86
3.34
2.43
1.72
1.30
1.21
0.89
48.2
48.3
30.3
20.1
20(R2)
30(R2)
d
d
d
d
d
d
d
d
d
d
d
d
d
d
d
30.4
20.1
30.4
20.2
13.8
30.3
20.1
40(R2)
10(R3)
20(R3)
30(R3)
40(R3)
d
d
d
d
d
d
d
a
13.8
29.2
d
13.7
29.3
d
13.7
b
2.77
d
28.0
d
d
136.4
130.7
128.3
128.4
2.88
d
28.2
d
d
e
d
f
137.0
d
h
c
c
c
g
d
d
d
7.25
7.35
7.35
e
e
f
f
g
g
h
h
d
d
d
d
d
d
d
d
d
d
d
d
d
d
d
d
a
138.3, 137.6 or 136.6.
137.8, 137.5, 137.2.
130.6, 130.5, 129.1, 129.0, 128.9, 128.8, 128.6, 128.4, 128.0.
130.5, 130.4, 130.4, 129.9, 129.3, 129.0, 128.9, 128.8, 128.5, 128.4.
7.45–7.10.
7.42–7.23, 6.99 (br s).
130.2, 129.1, 128.8, 128.6, 128.2, 128.1.
7.67–7.26 (br s).
b
c
d
e
f
g
h

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A. Klasek et al. / Tetrahedron 66 (2010) 2015–2025
2017
73.4 ppm (if R2¼H) or 77.5–79.0 ppm (if R2¼Bu). The occurrence of
13C NMR shifts of the thioxo group in a narrow region of 183.4–
184.8 ppm, typical of the C]S group, excludes the presence of
tautomeric compounds bearing a C–SH group that could theoreti-
cally arise from compounds 3a–d. These results are consistent with
those recorded from the 3-butyl analogs of compounds 3.4
In only one casedstarting from compound 1c and phenyl iso-
thiocyanate (Table 1, entry 4)dwas an acyclic compound (2d) iso-
lated in significant quantities. The major product appears almost
entirely as the open form 2d immediatelyafterdissolution in DMSO-
d6. Proton chemical shifts at 10.00 and 8.98 ppm were assigned to
–NHC(]S)NH– fragment, and characteristic 13C resonances were
observed at 187.8 (C]O),180.4 (C]S) and 73.5 (C-3) ppm. However,
the compound 2d appears to cyclize rapidly to 3d in DMSO-d6 thus,
a complete assignment of other resonances was impossible. The 1H
and 13C chemical shifts of compound 3d are given in Table 2.
The molecular rearrangement of compounds 3 was carried out
in accordance with our earlier papers4,5 by boiling in acetic acid or
concentrated hydrochloric acid. The results are presented in Table
3. A suggested reaction mechanism for the rearrangement of
compounds 3 (Scheme 2) is similar to that of their oxaanalogues.1
After protonation and loss of water, cationic intermediate A arises
and subsequently rearranges to intermediate B through migration
of the amide group from the 3a to the 9b position. In the case of 2d,
its cyclization to 3d must proceed in advance. Further trans-
formation of intermediate B proceeds either by elimination of
a proton to give spiro-compounds 4a–d, or by addition of water and
formation of two racemic 4R
*
5R
*
and 4R
*
*
5S spiro-compounds 5e–
h. We do not exclude the possibility that compounds 5 are formed
initially and subsequently dehydrate to 4 in cases when R2¼H. The
molecular rearrangement of compounds 3 was carried out in ac-
cordance with our earlier papers4,5 by boiling in acetic acid or
concentrated hydrochloric acid. The results are presented in Table
3. A suggested reaction mechanism for the rearrangement of
compounds 3 (Scheme 2) is similar to that of their oxaanalogues.1
After protonation and loss of water, cationic intermediate A arises
and subsequently rearranges to intermediate B through migration
of the amide group from the 3a to the 9b position. In the case of 2d,
its cyclization to 3d must proceed in advance. Further trans-
formation of intermediate B proceeds either by elimination of
a proton to give spiro-compounds 4a–d, or by addition of water and
formation of two racemic 4R*5R* and 4R*5S* spiro-compounds 5e–
h. We do not exclude the possibility that compounds 5 are formed
initially and subsequently dehydrate to 4 in cases when R2¼H.
NMR spectral characteristics of compounds 4 are given inTable 4.
The structure of 4a was confirmed by single crystal X-ray diffraction,
revealing distances and angles particular to the proposed bonding
arrangement (Fig. 1). Compounds 5e–h exhibit in their 13C NMR
spectra two sp3-C signals in the regions of 77.2–80.6 ppm (C(4)) and
94.4–98.2 ppm (C(5)) (Table 5), whereas only one signal for an sp3-C
atom (C(4)) appears in the region of 82.5–84.3 ppm for compounds
4 (Table 4). These values are in accord with those observed for the 2-
oxaanalogues of compounds 4 (76.2–77.8 ppm) and 5 (74.8–76.1 and
91.4–93.4 ppm).1
Table 3
Molecular rearrangement of compounds 2 and/or 3 in boiling AcOH (Method A) and
concd hydrochloric acid (Method B)a
Entry
Starting
Method
Time (h)
Products (yield, %)
compound
1
2
3
4
5
6
3a
3a
3b
3b
3c
3c
A
B
A
B
A
B
2.5
2
3
3
4
4a (44)
6a (52)
4b (33), 3b (34)
4b (11), 5Ab (19)
4c (70)
3
4c (2), 8c$HCl (5), 9c (11),
NPIb (7)
7
8
9
10
11
12
13
14
15
16
2d
2d
3e
3e
3f
A
B
A
B
A
B
A
B
A
B
3.5
3
1
3
3
1
3
2
3
4d (22), 2d (30), 7d (13)
4d (18)
5Ae (18), 5Be (29)
5Ae (4), 6e (26), 3e (10)c
5Af (24), 5Bf (36)
5Af (9), 5Bf (61)
5Ag (57)
5Ag (58), 5Bg (12)
5Ah (19), 5Bh (33)
5Bh (37)
Two stereogenic centers at C(4) and C(5) are present in com-
pounds 5. Indeed, two racemates 5A and 5B were formed after
rearrangement (Table 3) due to nonstereospecific addition of water
to carbocation B (Scheme 2). According to TLC in several solvent
systems, the corresponding pairs 5A/5B differed in their Rf values,
and each racemate was chromatographically pure. The structures of
two epimeric racemates corresponding to 5f were confirmed by X-
ray diffraction analysis (Figs. 2 and 3). The ORTEP view of the first
racemic diastereoisomer (Fig. 2) shows the presence of two
3f
3g
3g
3h
3h
3
a
For key of substituents see Table 1.
N-Phenylisatin, identical to the authentic compound.
Recovered starting material.
b
c
S
S
S
N
R2
R3
R3
S
R3
3
2
N
N
N
R3
N
HO
1
N
R2
H+
- H2O
N
R2
N
R2
Ph
5´
H2O
- CO2
4
5
1´
2´
NH
R1
Ph
Ph
O
Ph
N
N
R1
O
N
R1
O
B
3´
6a,e
3
A
R1
+ H2O, - H+
2d
AcOH
S
R2
S
1
N
2
4
2
1
N
3
N
3´a
3
O
OH
R3
R3
5
5
8
N
4
NHCOCH3
Ph
4´
4´
3
Ph
Ph
3´a
5
4
5´
6´
- H2O
5´
6´
2´
O
2´
O
2
N
R1
/
1´
N
1´
N
O
7´a
4a-e
5
7´a
1
7´
7´
1´
R1
7d
6´
5´
if R2 = H
For key of substituents see Table 1 and Scheme 1
2´
3´
2
if R = H
(with the exception of 5Bb)
two racemates
(4R*,5S*)-5A
4´
(4R*,5R*)-5B
Scheme 2.

´
A. Klasek et al. / Tetrahedron 66 (2010) 2015–2025
2018
Table 4
1H and 13C chemical shifts (
d, ppm) of compounds 4 and 6 in DMSO-d6
Position
4a
4b
4c
4d
6a
6e
dH
dC
dH
dC
dH
dC
dH
dC
dH
dC
dH
dC
1
2
3
4
d
d
d
d
d
d
d
d
d
ꢀ215.6a
161.6
ꢀ217.5a,b
124.8
124.3
113.0
149.0
109.9
d
d
d
d
194.2
d
d
195.2
d
d
194.4
d
d
195.1
d
d
d
161.3
d
d
d
d
d
12.73
d
d
d
82.5
180.3
d
d
84.3
180.2
d
d
82.6
180.1
d
d
84.2
179.9
d
d
124.8
127.9
112.2
149.2
109.6
d
5
d
d
d
d
d
d
10
d
d
d
d
d
d
20
d
167.5
d
d
167.9
d
d
167.2
d
d
167.6
d
d
d
30
d
d
d
d
6.72
d
6.58
d
30a
40
d
121.6
125.4
124.9
132.7
d
d
121.8
125.9
124.4
132.1
d
d
121.3
125.7
125.3
132.5
d
d
121.7
126.5
125.2
132.4
d
7.25
7.18
7.64
d
7.58
7.16
7.50
d
7.40
7.27
7.59
d
7.66
7.19
7.40
d
7.39
6.68
7.02
d
131.3
115.8
132.0
ꢀ325.4a,c
d
7.22
6.55
7.02
d
130.8
115.2
132.5
d
50
60
NHR1
70
7.46
d
111.3
143.9
128.3
128.5
130.2
134.8
27.6
d
7.23
d
111.0
143.9
128.2
128.5
129.9
134.6
27.4
d
7.09
d
111.7
143.6
128.3
128.2
130.0
134.6
132.9
126.7
130.2
129.4
d
6.78
d
111.2
143.2
d
d
d
7a0
d
d
d
d
10(5)
20(5)
30(5)
40(5)
10(R1)
20(R1)
30(R1)
40(R1)
10(R2)
d
d
d
d
128.0
d
128.7
125.5
128.5
127.2
29.9
d
128.8
128.4
130.4
128.7
29.9
d
d
7.62
7.50
7.66
3.42
d
7.67
7.53
7.70
3.26
d
7.77
7.60
7.70
d
7.78
7.66
7.70
d
f
7.36
7.26
7.22
2.71
d
7.39
7.39
7.39
2.67e
d
d
134.8
132.7
7.65
7.70
7.60
d
126.3
d
f
f
c
d
d
d
d
d
d
d
d
c
d
d
d
d
d
d
d
d
d
d
d
d
d
d
12.73
d
4.02
3.93
1.58
1.15
0.75
3.28
d
44.6
20(R2)
30(R2)
40(R2)
10(R3)
20(R3)
30(R3)
40(R3)
d
d
d
d
d
d
d
d
d
d
d
d
d
d
d
30.0
19.3
13.4
32.0
d
d
d
d
d
d
d
d
d
d
d
d
d
d
d
d
d
2.95
d
30.1
d
d
136.7
128.1
129.5
129.2
3.11
d
30.2
d
135.6
3.17
d
31.1
d
d
7.10
7.40
7.36
7.12
f
d
d
d
d
d
d
d
d
d
d
f
d
d
d
d
d
d
d
d
a
d (
15N).
b
c
d
e
f
1J (15N,1H)¼98.6 Hz.
1J (15N,1H)¼93.4 Hz.
130.3, 130.1, 129.7, 129.5, 129.4, 128.6, 128.2.
d
(1H)¼5.36 (NH).
7.61–7.22.
independent molecules with 4R,5S and 4S,5R configuration
((4R ,5S )-5Af) in the crystal unit cell. By contrast, the corre-
*
*
sponding ORTEP view of the second epimeric racemate (Fig. 3)
shows only one symmetrically independent molecule having both
carbon atoms (C(4) and C(5)) in R,R configuration. Naturally, in Pꢀ1,
the corresponding molecule with S,S configuration is also present.
Therefore, this compound can be designed as (4R
*
,5R )-5Bf. The
*
biggest difference between these otherwise similar samples is the
fact that the strong intermolecular O–H/O]C hydrogen contact is
present between two enantiomeric forms in the case of
the(4R
*
,5S
*
)-5Af, forming thus a linear chain. On the other hand,
,5R )-5Bf,
between two enantiomeric forms represented by (4R
*
*
such a contact is not observed, and intramolecular hydrogen
bonding takes place instead. For views of H-bonding in 5Af and 5Bf,
see Supplementary data. The MS of corresponding pairs 5A/5B is
almost identical. From an analysis and mutual comparison of NMR
spectra (Table 5) of the rearrangement products from 3e–h it fol-
lows that 5Ae, 5Af, 5Ag and 5Ah are also pure racemic di-
astereoisomers with (4R
5Be, 5Bf, 5Bg and 5Bh are pure epimeric diastereoisomers with
a (4R ,5R ) configuration. It is interesting to note, that compound
(4R ,5S )-5Abdwhich bears a hydroxyl group, and could theoreti-
*
,5S
*
) configuration, and that compounds
*
*
*
*
cally provide 4b upon acid-catalyzed dehydrationdarises simul-
taneously with 4b by rearrangement of 3b (Table 3).
In two cases (Table 3, entries 2 and 10), compounds 6 were
isolated upon rearrangement of compounds 3 in concentrated
hydrochloric acid. It is evident that these compounds arise by
hydrolysis of the lactam ring of compounds 3 (or, perhaps,
Figure 1. ORTEP view of compound 4a showing the thermal ellipsoids at 50% prob-
ability (arbitrary spheres for H atoms). For selected interatomic distances and angles
see Supplementary data.

´
A. Klasek et al. / Tetrahedron 66 (2010) 2015–2025
2019
Table 5
1H and 13C chemical shifts (
d, ppm) of compounds 5A and 5B in DMSO-d6
Position
5Ab
5Ae
5Be
5Af
5Bf
5Ag
5Bg
5Ah
5Bh
dH
dC
dH
dC
dH
dC
dH
dC
dH
dC
dH
dC
dH
dC
dH
dC
dH
dC
2
4
d
184.1
72.9
d
185.7
79.2
d
184.1
77.2
d
185.7
80.6
d
183.2
78.1
d
185.9
79.3
d
184.2
77.4
d
185.8
80.4
d
183.2
78.2
d
d
d
d
d
d
d
d
d
5
d
91.4
d
94.4
d
97.2
d
95.3
d
97.9
d
94.6
d
97.6
d
95.5
d
98.2
20
d
172.1
121.1
128.0
122.4
130.6
108.8
143.4
d
d
171.9
120.4
128.3
122.3
130.7
108.6
144.6
d
d
172.0
121.7
125.5
121.5
130.4
108.8
145.3
d
d
172.4
120.4
128.9
122.0
130.4
108.3
144.1
d
d
172.7
121.6
126.4
121.2
130.2
108.6
144.9
d
d
171.5
120.1
128.8
122.9
130.8
108.9
144.3
d
d
171.5
121.6
126.0
122.2
130.5
108.9
144.7
d
d
172.1
120.1
129.6
122.6
130.6
108.6
143.8
d
d
172.3
121.4
126.9
121.8
130.3
108.9
144.4
d
3a0
40
d
d
d
d
d
d
d
d
d
7.52
7.10
7.33
6.90
d
7.74
7.21
7.45
6.91
d
5.56
6.61
7.29
7.03
d
7.89
7.11
7.32
6.73
d
5.54
6.47
7.15
6.88
d
7.85
7.28
7.43
6.55
d
5.70
6.63
7.19
6.71
d
7.97
7.16
7.25
6.37
d
5.65
6.52
7.08
6.60
d
50
60
70
7a0
OH
10(5)
20(5)
30(5)
40(5)
10(R1)
7.30
d
7.35
d
7.46
d
7.71
d
7.66
d
7.50
d
7.60
d
7.83
d
7.85
d
133.8
135.3
127.3
127.4
128.8
25.7
137.9
128.2
128.2
129.2
26.4
134.8
127.6
127.7
129.0
25.6
137.9
128.3
128.3
129.4
26.4
135.5
127.7
127.7
129.2
133.2
137.8
128.2
128.2
129.3
134.1
135.0
127.9
137.8
128.7
128.4
129.5
44.2
a
b
7.04
7.27
7.33
2.59
6.94
7.39
7.42
3.18
7.11
7.29
7.36
2.50
7.07
7.42
7.46
3.14
7.11
7.35
7.40
d
6.94
7.34
7.39
d
7.17
7.15
7.50
7.50
4.00
3.07
1.80
1.76
1.37
0.92
d
a
a
b
b
c
d
c
d
3.00
26.1
3.63
3.54
2.06
2.01
1.29
0.92
d
45.3
20(R1)
d
d
d
d
d
d
d
d
d
d
d
d
d
d
6.61
126.3
7.45
126.7
30.5
30.5
d
d
d
d
d
d
d
d
d
30(R1)
40(R1)
10(R2)
d
d
d
d
d
d
d
d
d
7.42
7.40
3.58
3.42
1.95
129.6
128.5
45.1
7.60
7.49
3.87
2.92
1.70
1.62
1.28
0.85
2.71
d
129.8
128.3
44.2
20.3
13.8
138.5
19.8
14.0
138.7
d
d
d
d
d
d
d
d
d
10.18
3.54
3.32
1.89
45.0
3.89
2.94
1.73
1.66
1.33
0.91
2.60
d
44.1
3.59
3.48
2.04
1.97
1.28
0.91
d
45.2
3.97
3.04
1.79
1.73
1.37
0.94
d
44.1
20(R2)
d
d
d
d
d
d
d
d
30.5
30.7
30.5
30.5
30.5
30.6
7.13
129.1
c
d
30(R2)
40(R2)
10(R3)
20(R3)
30(R3)
40(R3)
1.25
0.89
2.74
d
20.2
13.8
31.5
d
19.8
14.0
31.4
d
20.2
13.8
138.6
128.7
129.7
127.7
19.8
14.0
138.3
129.1
128.6
127.4
1.27
0.90
2.88
d
20.2
14.0
31.5
d
19.8
13.8
31.7
d
7.28
7.20
d
128.7
127.6
133.9
126.5
129.9
129.5
c
c
d
d
d
a
137.7
d
133.0
126.0
b
7.30
7.24
7.30
7.02
7.21
7.14
6.45
7.38
7.64
7.53
a
a
b
b
c
d
d
d
d
d
d
d
d
d
c
d
d
d
d
d
d
d
d
d
a
7.34–7.00.
b
129.7, 129.1, 128.8, 128.7, 128.2, 126.7.
7.46–7.23.
129.6, 129.5, 129.1, 128.8, 127.9, 127.7.
c
d
Figure 2. ORTEP view of compound 5Af showing the thermal ellipsoids at 30%
probability (arbitrary sphere for H atom, one of the isomers is shown only, H atoms
except of O–H one are omitted for clarity). For selected interatomic distances and
angles see Supplementary data.
intermediates A or B) with subsequent decarboxylation. The 15N
NMR spectra of compound 6a (Table 4) clearly show that two NH
groups (see 1J (15N, 1H)¼98.6 Hz) are present in this compound;
therefore, it must contain a C]S group and the formation of the
possible –SH tautomer is excluded. The structure of 6a was con-
firmed by single crystal X-ray diffraction (Fig. 4).
Figure 3. ORTEP view of compound 5Bf showing the thermal ellipsoids at 30%
probability (arbitrary spheres for H atoms). For selected interatomic distances and
angles see Supplementary data.

´
A. Klasek et al. / Tetrahedron 66 (2010) 2015–2025
2020
The origin of compounds 8c and 9c can be explained by the
transformation of the intermediate carbocation Bc, or of com-
pound 5c, which arises temporarily from Bc (Scheme 3). We
propose that compound 5c rearrange through intermediate Cc in
a manner similar to that of its previously described oxaana-
logue.10,11 Nucleophilic attack in intermediate Cc leads to the in-
termediate Dc, which provides compound 8c after dehydration
and hydrolysis. By comparing elemental composition of com-
pounds 3c and 9c, it follows that an oxidation process must pro-
ceed during the reaction. We are convinced that the intermediate
Cc reacts with atmospheric oxygen to provide intermediate Ec,
which after hydrolysis, protonation and elimination of benzoic
acid affords carbocation Fc and, subsequently, compound 9c. This
proposed reaction mechanism is supported by the isolation of N-
phenylisatine (Table 3), which arises from the hydrolysis of in-
termediate Ec.
3. Conclusions
In conclusion, we would like to emphasize that the described
method affords the new spiro-oxindoles 4 and 5 in good to very
good yields. The molecular rearrangement of compounds 3 not only
has theoretical significance, but also offers a simple procedure for
the preparation of new spiro-oxindoles suitable for biological
Figure 4. ORTEP view of compound 6a showing the thermal ellipsoids at 50% prob-
ability (arbitrary spheres for H atoms). For selected interatomic distances and angles
see Supplementary data.
S
S
H
S
H
H3C
H3C
N
N
S
Ph
H3C
N
N
H3C
N
N
NHCOPh
Ph
O
H2O
N
COPh
H
O
O
O
- CO2
OH
N
N
N
N
Cc
Bc
Dc
5c
Ph
Ph
Ph
Ph
H+, H2O
O2
- PhCOOH
S
S
1
2
S
NH
NH
H3C
H3C
3
N
4´a
1
5
S
H3C
O
N
O
N
HO
H3C
N
4
8
5
NHCOPh
8a 1
8´b
2
NH
6´
7´
H+, H2O
+
3´
2´
9´
4´
5´
O
3
- PhCOOH
3a
N
N
N
H
N
4´b
8´a
4a
Ec
8c
Fc
1´
H
8´ 9c
Ph
Ph
Scheme 3.
The structure of 6a reveals several interesting features of the
five-membered diaza heterocyclic ring. The interatomic distance
C2–C3 is a bit elongated in comparison to the formal double bond
distance;7 but at the same time other distances within the same
ring (C–N and C]S) are significantly shortened, indicating a high
degree of conjugation within this system. Two of these molecules
are interconnected via a N–H/S]C bridge (see Supplementary
data). An intramolecular connection to the N–H group is precluded
by the absence of the suitably positioned acceptor of electron
density. Previously, we have only observed the formation of com-
pounds similar to 6 during the rearrangement of oxaanalogues of 3
that lack a substituent at position 5.8,9
In one case, namely for the rearrangement of 2d, we also iso-
lated compound 7d (Table 3), which arises by the acidolysis of the
starting compound 2d with acetic acid. Its structure was con-
firmed by the acetylation of 1d with acetic anhydride in pyridine.
Two other side reaction products (8c$HCl and 9c) were obtained
from the rearrangement of 3c in boiling hydrochloric acid (Table
3). The structure of both products was firmly established by the
assignment of all resonances undoubtedly using 2D NMR spectra.
testing, as well as for further synthetic elaboration. Compounds 4
and 5 have not been described previously in the literature; only
their 2-oxoanalogues have been previously synthesized.1 The pre-
sented results expand the number of described of compounds
containing the spiro-oxindole structural motif, which notably ap-
pears in several indole alkaloids,12 and in other compounds
exhibiting various biological activities.13,14 Our results also increase
the variety of methods for preparing spiro-oxindoles.13 At the same
time, we have expanded the number of characterized compounds
that contain the 4,4-spiro-2-thioxoimidazoline structural fragment.
With the exception of compounds described in our previous paper,4
relatively few compounds within this class have been described in
the literature. Previously described compounds contain a cyclo-
hexylidene,15,16 cyclopentylidine,16 or dihydroacridinyl group17 as
the second component of the spiro-structure. Since a number of
simple N-substituted 2-thioxoimidazolines are known to exhibit
inflammatory activity,18 gentamycin nephrotoxicity,19 dopamine
b-
hydroxylase inhibitory activity and anti-aggregating activity
against collagen,20 compounds 4, 5, and 6 have the potential to
display significant biological activity.

´
A. Klasek et al. / Tetrahedron 66 (2010) 2015–2025
2021
4. Experimental
4.1. General
to the protocol described in literature.6 One new amine was
prepared.
4.2.1. 3-Amino-1,3-diphenyl-1H,3H-quinoline-2,4-dione (1c). To
a
Melting points were determined on a Kofler block or Gallencamp
apparatus. IR (KBr) spectra were recorded on a Mattson 3000 spec-
trophotometer. 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 DMSO-d6 or CDCl3. 1H and 13C chemical shifts are given on the
stirred suspension of powdered ammonium chloride (5.35 g,
100 mmol) and potassium carbonate (27.65 g, 200 mmol) in DMF
(250 mL), a solution of 3-chloro-1,3-diphenyl-1H,3H-quinoline-2,4-
dione (17.4 g, 50 mmol) in DMF (125 mL) was added dropwise at
0 ꢁC. The stirring was continued at rt for 24 h. The reaction mixture
was poured into ice-water (2 L) and precipitated amine 1c was
filtered off. From the filtrate, the second part of the amine 1c was
extracted with benzene (five times, 100 mL each). The collected
extracts were dried over anhydrous sodium sulfate, evaporated to
dryness and the residue was crystallized from benzene–hexane.
Combined portions of crude product 1c were dissolved in hydro-
chloric acid (18%, 300 mL) and the solution was washed three times
with benzene (each 100 mL). Aqueous layer was made alkaline with
concentrated aqueous ammonia, the precipitated amine was fil-
tered off, dried and crystallized from benzene. Yield 8.5 g (52%) of
colourless plates, mp 158–160 ꢁC (benzene), Rf 0.21 (S3); IR: 3388,
3318, 3061, 3032, 1709, 1675, 1598, 1491, 1460, 1336, 1299, 1245,
1191, 1158, 1105, 1073, 1033, 982, 945, 874, 836, 807, 765, 698, 690,
d
scale (parts per million) and are referenced to internal TMS. 15N
chemical shifts were referred to external neat nitromethane in co-
axial capillary (
¼0.0). All 2D experiments (gradient-selected (gs)-
d
COSY, NOESY, gs-HMQC, gs-HMBC) were performed using
manufacturer’s software. Proton spectra were assigned using gs-
COSY. Protonated carbons were assigned by gs-HMQC. Quaternary
carbons were assigned by gs-HMBC. The positive- and negative-ion
APCI mass spectra were measured on an ion trap analyzer Agilent
LC-MSD Trap XCT-Ultra (Agilent, Palo Alto, CA, USA) within the mass
range m/z¼50–500. Samples were dissolved in acetonitrile and ana-
lyzed after direct injection (2 mL) at the flow rate of 400 mL/min
acetonitrile. The ion source temperature was 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 ampli-
tude was 0.8 V. Column chromatography was carried out on Silica gel
(Merck, grade 60, 70–230 mesh) using chloroform and then succes-
sive mixtures of chloroform–ethanol (in rations from 99:1 to 8:2,
solvent system S1) or benzene and then successive mixtures of
benzene–ethylacetate (inrationsfrom 99:1to8:2,solventsystemS2).
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). Elemental analyses (C, H, N) were performed with
a EA 1108 Elemental Analyzer (Fisons Instrument).
646, 595, 562, 515 cmꢀ1 1H NMR (DMSO-d6):
. d 2.70 (s, 2H, NH2),
6.40 (d, J¼8.2 Hz, 1H, H-8), 7.20 (m, 1H, H-3), 7.35 (m, 1H, H-40(3-
Ph)), 7.41 (m, 2H, H-30(3-Ph) and H-50(3-Ph)), 7.45 and 7.25 Hz (br
s), 2H, H-20(N–Ph) and H-60(N–Ph)), 7.49 (m, 1H, H-7), 7.52 (m, 2H,
H-20(3-Ph) and H-60(3-Ph)), 7.60 (m, 1H, H-40(N–Ph)), 7.69 (m, 2H,
H-30(N–Ph) and H-50(N–Ph)), 7.86 (d, J¼7.8 Hz, 1H, H-5); 13C NMR
(DMSO-d6): d 71.8 (C-3), 116.7 (C-8), 120.3 (C-4a), 123.4 (C-6), 125.9
(C-20(3-Ph) and C-60(3-Ph)), 127.5 (C-5), 128.4 (C-40(3-Ph)), 129.0
(C-40(N–Ph)), 129.1 (C-30(3-Ph) and C-50(3-Ph)), 130.3 (C-20(N–Ph)
and C-60(N–Ph)), 130.5 (C-30(N–Ph) and C-50(N–Ph)), 135.8 (C-7),
137.7 (C-10(N–Ph)),140.3 (C-10(3-Ph),143.4 (C-8a),172.0 (C-2),193.4
(C-4). Positive-ion APCI-MS: m/z 329 [MþH]þ (100%); positive-ion
APCI-MS/MS of m/z 328: 312 [MþHꢀNH3]þ, 284 [MþHꢀNH3ꢀCO]þ
(100%). Anal. Calcd (found) for C21H16N2O2: C 76.81 (76.62); H 4.91
(4.97); N 8.53 (8.61).
X-ray analysis: Single crystals of 4a and 6a were prepared by slow
crystallization from ethyl acetate and acetic acid, respectively, single
crystals of 5Af and 5Bf were obtained by liquid diffusion method21
using dichloromethane–hexane and acetic acid–hexane, re-
spectively, as solvent–precipitant pairs. The X-ray data of all com-
pounds were obtained at 150 ꢁK using Oxford Cryostream
low-temperature device on a Nonius KappaCCD diffractometer with
4.3. General method for the preparation of 3-thioureido-
1H,3H-quinoline-2,4-diones (2) and 9b-hydroxy-3a-phenyl-
1,2,3,3a-tetrahydro-2-thioxo-5H-imidazo[4,5-c]quinolin-
4(9bH)-ones (3)
Mo K
a
radiation (
l
¼0.71073 Å), a graphite monochromator and the
4
and
c
scan mode. Data reductions were performed with DENZO-
SMN.22 The absorption was corrected by integration methods.23
Structures were solved by direct methods(Sir92)24 andrefined byfull
matrix least-square based on F2 (SHELXL97).25 Hydrogen atoms were
mostly localized on a difference Fourier map, however to ensure
uniformity of treatment of crystal, all hydrogen were recalculated
into idealized positions (riding model) and assigned temperature
factors Hiso(H)¼1.2Ueq (pivot atom) or of 1.5Ueq for the methyl moiety
with C–H¼0.96, 0.97 and 0.93 Å for methyl, methylene and hydrogen
atoms in aromatic ring, respectively, and 0.82 Å for O–H group.
Crystallographic data for structural analysis have been deposited
with the Cambridge Crystallographic Data Centre, CCDC nos. 725189,
725190, 725191 and 725188 for 4a, 5Af, 5Bf and 6a, respectively.
Copies of this information may be obtained free of charge from The
Director, CCDC, 12 Union Road, Cambridge CB2 1EY, UK (fax: þ44
1223 336033; e-mail: deposit@ccdc.cam.ac.uk or www: http://
Phenyl isothiocyanate (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). After stirring at
rt for 3 h, the solution was heated to reflux for the time given in
Table 1. The course of the reaction was monitored by TLC. After
cooling and evaporating in vacuo to dryness, the residue was
crystallized from appropriate solvent. In the case of the reaction of
1a with phenyl isothiocyanate, the residue was column chroma-
tographed. Yields are given in Table 1, NMR data are presented in
Table 2.
4.3.1. 1,5-Dimethyl-9b-hydroxy-3a-phenyl-1,2,3,3a-tetrahydro-2-thi-
oxo-5H-imidazo[4,5-c]quinolin-4(9bH)-one (3a). Colourless needles,
mp 235–238 ꢁC (ethyl acetate), Rf 0.68 (S4); IR: 3401, 3264, 2975,
2931, 1671, 1657, 1604, 1473, 1393, 1361, 1286, 1223, 1175, 1147, 1135,
1108, 1094, 1080, 1066, 1041, 1027, 977, 909, 853, 807, 762, 726, 703,
674, 650, 588, 570 cmꢀ1. Positive-ion APCI-MS: m/z 340 [MþH]þ
(100%), 322 [MþHꢀH2O]þ, 306, 267 [MþHꢀCH3NCS]þ; positive-ion
APCI-MS/MS of m/z 340: 267 [MþHꢀCH3NCS]þ (100%), 250
[MþHꢀCH3NHCSNH2]þ, 222. Negative-ion APCI-MS: m/z 338
[MꢀH]ꢀ (49%), 321 [MþHꢀOH]þ, 250 (100%); negative-ion APCI-MS/
MS of m/z 338: 290, 281 [MꢀHꢀC4H9]ꢀ, 205 [MꢀHꢀC4H9NCSꢀH2O]ꢀ
www.ccdc.cam.ac.uk). In the case of crystals (4R
*
,5R )-5Bf, there are
*
rather high R value parameters because bad quality of crystals.
4.2. Preparation of 3-amino-1H,3H-quinoline-2,4-diones (1)
Starting 3-substituted 3-amino-1H,3H-quinoline-2,4-diones (1)
were prepared from corresponding 3-chloro derivatives according

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A. Klasek et al. / Tetrahedron 66 (2010) 2015–2025
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(100%). Anal. Calcd (found) for C18H17N3O2S: C 63.70 (63.91); H 5.05
(5.21); N 12.38 (12.41).
MS: m/z 394 [MꢀH]ꢀ (40%), 250 (100%). Negative-ion APCI-MS/MS
of m/z 394: 379 [MꢀHꢀCH3]ꢀ, 350 [MꢀHꢀC3H8]ꢀ, 261
[MꢀHꢀC4H9NCSꢀH2O]ꢀ (100%). Anal. Calcd (found) for
C22H25N3O2S: C 66.81 (66.70); H 6.37 (6.42); N 10.62 (10.81).
4.3.2. 1,3a-Diphenyl-9b-hydroxy-5-methyl-1,2,3,3a-tetrahydro-2-thi-
oxo-5H-imidazo[4,5-c]quinolin-4(9bH)-one (3b). Colourless plates,
mp 205–208 ꢁC (ethyl acetate), Rf 0.36 (S4); IR: 3298, 3032, 2940,
2874, 1667, 1606, 1497, 1473, 1439, 1409, 1382, 1360, 1298, 1270,
1260, 1213, 1149, 1069, 1054, 1006, 972, 930, 910, 853, 812, 764, 711,
695, 653, 621, 577 cmꢀ1. Positive-ion APCI-MS: m/z 402 [MþH]þ
(100%), 267 [MþHꢀC6H5NCS]þ; positive-ion APCI-MS/MS of m/z
402: 267 [MþHꢀC6H5NCS]þ (100%), 250 [MþHꢀC6H5NHCSNH2]þ.
Negative-ion APCI-MS: m/z 400 [MꢀH]ꢀ (100%); negative-ion
APCI-MS/MS of m/z 400: 281 [MꢀHꢀC6H5NCO]ꢀ (100%). Anal.
Calcd (found) for C23H19N3O2S: C 68.81 (68.57); H 4.77 (4.59); N
10.47 (10.42).
4.3.7. 3-Butyl-1,3a-diphenyl-9b-hydroxy-5-methyl-1,2,3,3a-tetra-
hydro-2-thioxo-5H-imidazo[4,5-c]quinolin-4(9bH)-one
(3f). Colourless cubes, mp 140–145 ꢁC and then 199–203 ꢁC (ben-
zene–cyclohexane), Rf 0.47 (S3); IR: 3418, 3254, 3063, 2954, 2928,
2870, 1676, 1604, 1495, 1470, 1399, 1368, 1284, 1224, 1133, 1106,
1055, 1019, 965, 855, 751, 715, 695, 661, 593, 518 cmꢀ1. Positive-ion
APCI-MS: m/z 458 [MþH]þ (30%), 323 [MþHꢀC6H5NCS]þ (100%);
positive-ion APCI-MS/MS of m/z 458: 323 [MþHꢀC6H5NCS]þ
(100%). Negative-ion APCI-MS: m/z 456 [MꢀH]ꢀ (100%); negative-
ion APCI-MS/MS of m/z 456: 412 [MꢀHꢀC3H8]ꢀ, 337
[MꢀHꢀC6H5NCO]ꢀ (100%), 323 [MꢀHꢀC4H9NCSꢀH2O]ꢀ, 264
[MꢀHꢀC4H9NCSꢀC6H5]ꢀ. Anal. Calcd (found) for C27H27N3O2S: C
70.87 (70.95); H 5.95 (5.71); N 9.18 (9.23).
4.3.3. 3a,5-Diphenyl-9b-hydroxy-1-methyl-1,2,3,3a-tetrahydro-2-
thioxo-5H-imidazo[4,5-c]quinolin-4(9bH)-one (3c). Colourless nee-
dles, mp 241–245 ꢁC (benzene), Rf 0.58 (S6); IR: 3223, 3011, 2973,
2933, 1680, 1604, 1489, 1458, 1398, 1347, 1301, 1261, 1227, 1152,
1132, 1071, 1031, 985, 946, 922, 824, 771, 751, 730, 710, 695, 653,
605, 573 cmꢀ1. Positive-ion APCI-MS: m/z 402 [MþH]þ (100%), 384
[MþHꢀH2O]þ, 368 [MþHꢀH2S]þ, 329 [MþHꢀCH3NCS]þ; positive-
ion APCI-MS/MS of m/z 402: 329 [MþHꢀCH3NCS]þ (100%). Nega-
tive-ion APCI-MS: m/z 400 [MꢀH]ꢀ (55%), 312 (100%); negative-ion
APCI-MS/MS of m/z 400: 205 [MꢀHꢀC6H5ꢀCH3NHCSNH2ꢀCO]ꢀ
(100%). Anal. Calcd (found) for C23H19N3O2S: C 68.81 (68.69); H 4.77
(4.87); N 10.47 (10.54).
4.3.8. 3-Butyl-3a,5-diphenyl-9b-hydroxy-1-methyl-1,2,3,3a-tetra-
hydro-2-thioxo-5H-imidazo[4,5-c]quinolin-4(9bH)-one
(3g). Colourless plates, mp 208–211 ꢁC (benzene), Rf 0.58 (S3); IR:
3364, 3066, 3039, 2954, 2934, 2859, 1670, 1603, 1494, 1461, 1407,
1364, 1352, 1296, 1173, 1151, 1130, 1099, 1055, 1031, 986, 942, 868,
823, 767, 751, 699, 660, 634, 622, 605, 590, 516 cmꢀ1. Positive-ion
APCI-MS: m/z 458 [MþH]þ (100%), 440 [MþHꢀH2O]þ, 424, 414
[MþHꢀC3H8]þ, 385 [MþHꢀCH3NCS]þ; positive-ion APCI-MS/MS of
m/z 520: 385 [MþHꢀCH3NCS]þ (100%). Negative-ion APCI-MS: m/z
456 [MꢀH]ꢀ (15%), 312 (100%); negative-ion APCI-MS/MS of m/z
4.3.4. 3-Thioureido-1,10,30-triphenyl-1H,3H-quinoline-2,4-dione
(2d). Colourless plates, mp 217–223 ꢁC (ethyl acetate–hexane), Rf
0.53(S6); IR:3346,1698,1651,1599,1561,1529,1493,1462,1339,1325,
1301, 1266, 1247, 1161, 1114, 1069, 1027, 986, 905, 878, 837, 778, 760,
744, 696, 660, 602, 566 cmꢀ1. Positive-ion APCI-MS: m/z 464 [MþH]þ
(100%), 329 [MþHꢀC6H5NCS]þ; positive-ion APCI-MS/MS of m/z 420:
329 [MþHꢀC6H5NCS]þ (100%), 312 [MþHꢀC6H5NHCSNH2]þ, 284
[MþHꢀC6H5NHCSNH2ꢀCO]þ. Negative-ion APCI-MS: m/z 462
[MꢀH]ꢀ (100%), 343 [MꢀHꢀC6H5NCO]ꢀ, 312; negative-ion APCI-MS/
MS of m/z 462: 343 [MꢀHꢀC6H5NCO]ꢀ (100%). In DMSO-d6 solution
changes into the mixture of 2d and 3d. Anal. Calcd (found)
for C28H21N3O2S: C 72.55 (72.45); H 4.57 (4.59); N 9.06 (9.01); S
6.92 (6.74).
456:
412
[MꢀHꢀC3H8]ꢀ
(65%),
261
[MꢀHꢀC6H5NHCOꢀC4H9ꢀH2O]ꢀ (100%). Anal. Calcd (found) for
C27H27N3O2S: C 70.87 (70.62); H 5.95 (6.05); N 9.18 (9.31).
4.3.9. 3-Butyl-9b-hydroxy-1,3a,5-triphenyl-1,2,3,3a-tetrahydro-2-
thioxo-5H-imidazo[4,5-c]quinolin-4(9bH)-one (3h). Colourless rods,
mp 209–212 ꢁC (benzene–hexane), Rf 0.44 (S3); IR: 3324, 3060,
3038, 2950, 2870, 1664, 1604, 1494, 1461, 1364, 1295, 1223, 1186,
1154, 1130, 1104, 1061, 1025, 1005, 944, 913, 809, 748, 715, 701, 660,
647, 622, 593, 536, 517 cmꢀ1. Positive-ion APCI-MS: m/z 520
[MþH]þ (27%), 486, 385 [MþHꢀC6H5NCS]þ (100%); positive-ion
APCI-MS/MS of m/z 520: 385 [MþHꢀC6H5NCS]þ (100%). Negative-
ion APCI-MS: m/z 518 [MꢀH]ꢀ (17%), 474 [MꢀHꢀC3H8]ꢀ, 312
(100%); negative-ion APCI-MS/MS of m/z 518: 474 [MꢀHꢀC3H8]ꢀ
(100%), 323 [MꢀHꢀC6H5NHCOꢀC4H9–H2O]ꢀ. Anal. Calcd (found)
for C32H29N3O2S: C 73.96 (73.81); H 5.62 (5.79); N 8.09 (8.30).
4.3.5. 9b-Hydroxy-1,2,3,3a-tetrahydro-1,3a,5-triphenyl-2-thioxo-
5H-imidazo[4,5-c]quinolin-4(9bH)-one (3d). Colourless cubes, mp
195–204 ꢁC (cyclohexane–ethyl acetate), Rf 0.57 (S6); IR: 3379, 3326,
3179, 3064, 1673, 1605, 1495, 1462, 1398, 1341, 1299, 1266, 1214,
1152, 1131, 1072, 1052, 1026, 1009, 647, 629, 829, 809, 756, 709, 696,
649, 621, 608, 575 cmꢀ1. Positive-ion APCI-MS: m/z 464 [MþH]þ
(100%), 329 [MþHꢀC6H5NCS]þ; positive-ion APCI-MS/MS of m/z
420: 329 [MþHꢀC6H5NCS]þ (100%), 312 [MþHꢀC6H5NHCSNH2]þ,
284 [MþHꢀC6H5NHCSNH2–CO]þ. Negative-ion APCI-MS: m/z 462
[MꢀH]ꢀ (100%), 343 [MꢀHꢀC6H5NCO]ꢀ, 312; negative-ion APCI-
MS/MS of m/z 462: 343 [MꢀHꢀC6H5NCO]ꢀ (100%). Anal. Calcd
(found) for C28H21N3O2S: C 72.55 (72.45); H 4.57 (4.59); N 9.06
(9.01); S 6.92 (6.74).
4.4. General methods for the molecular rearrangement of
compounds 2 and 3
Method A: The solution of starting compound 2 or 3 (1 mmol) in
acetic acid (8 mL) was heated to reflux for the time given in Table 3.
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. Yields are given in Table 3,
NMR data are presented in Tables 4 and 5.
Method B: The solution of starting compound 2 or 3 (1 mmol) in
concd hydrochloric acid (5 mL) was heated to reflux for the time
given in Table 3. In same cases a small quantity of acetic acid was
added to dissolution of starting compound. The course of the re-
action was monitored by TLC. After cooling, the reaction mixture
was evaporated to dryness in vacuo and the residue was dissolved
in pyridine. The solution was evaporated to dryness and the residue
was crystallized from appropriate solvent or separated by column
chromatography on silica gel. In the case of starting compound 3c,
a portion of the reaction mixture was insoluble in pyridine. This
4.3.6. 3-Butyl-1,5-dimethyl-9b-hydroxy-3a-phenyl-1,2,3,3a-tetra-
hydro-2-thioxo-5H-imidazo[4,5-c]quinolin-4(9bH)-one
(3e). Colourless plates, mp 205–210 ꢁC (benzene), Rf 0.65 (S3); IR:
3430, 2959, 2934, 2861, 1657, 1604, 1498, 1465, 1444, 1424, 1402,
1367, 1301, 1277, 1227, 1176, 1156, 1135, 1101, 1046, 981, 936, 849,
804, 774, 758, 703, 668, 652, 580, 547 cmꢀ1. Positive-ion APCI-MS:
m/z 396 [MþH]þ (100%), 378 [MþHꢀH2O]þ, 352 [MþHꢀC3H8]þ,
323 [MþHꢀCH3NCS]þ; positive-ion APCI-MS/MS of m/z 396: 378
[MþHꢀH2O]þ, 323 [MþHꢀCH3NCS]þ (100%). Negative-ion APCI-

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A. Klasek et al. / Tetrahedron 66 (2010) 2015–2025
2023
portion was filtered off with suction and recrystallized from etha-
nol to give 8c$HCl.
[MþHꢀH2O]þ, 323 [MþHꢀCH3NCS]þ, 281 [MþHꢀC4H9NCS]þ,
258 [MþHꢀC3H8ꢀC6H5ꢀOH]þ (100%); positive-ion APCI-MS/MS
of m/z 378: 336, 322 [MþHꢀH2OꢀC4H8]þ (100%), 264
[MþHꢀH2OꢀC4H8NCS]þ. Negative-ion APCI-MS: m/z 394 [MꢀH]ꢀ
(100%), 250; negative-ion APCI-MS/MS of m/z 394: 379
[MꢀHꢀCH3]ꢀ (100%), 137. Anal. Calcd (found) for C22H25N3O2S: C
66.81 (66.69); H 6.37 (6.51); N 10.62 (10.51).
4.4.1. 10,3-Dimethyl-5-phenyl-2-thioxospiro[4H-imidazol-4,30-
[3H]indol]-20(10H,3H)-one (4a). Yellow needles, mp 236–239 ꢁC
(ethanol), Rf 0.50 (S3); IR: 2968, 2922, 1726, 1716, 1611, 1540, 1489,
1468, 1445, 1389, 1360, 1348, 1325, 1305, 1281, 1265, 1238, 1165,
1128, 1092, 1008, 938, 874, 841, 805, 779, 753, 699, 668, 614, 588,
537 cmꢀ1. For 1H and 13C NMR see Table 4. Positive-ion APCI-MS:
m/z 322 [MþH]þ (100%), 290 [MþHꢀS]þ; positive-ion APCI-MS/MS
of m/z 322: 290 [MþHꢀS]þ, 289 [MþHꢀSH]þ, 263 [MþHꢀNHCS]þ
(100%), 247 [MþHꢀNCSꢀOH]þ, 222, 221. Anal. Calcd (found) for
C18H15N3OS: C 67.27 (67.39); H 4.70 (6.69); N 13.07 (13.21).
4.4.7. (4R*,5R*)-1-Butyl-10,3-dimethyl-5-hydroxy-5-phenyl-2-thio-
xospiro[imidazolidin-4,30-[3H]indol]-20-one (5Be). Colourless nee-
dles, mp 174–177 ꢁC (benzene), Rf 0.51 (S3); IR: 3455, 3065, 2957,
2930, 2869, 1721, 1613, 1467, 1408, 1368, 1297, 1262, 1163, 1094,
1071, 1005, 988, 927, 828, 754, 700, 656 cmꢀ1. Positive-ion APCI-
MS: m/z 396 [MþH]þ (15%), 378 [MþHꢀH2O]þ (100%), 352
[MþHꢀC3H8]þ; positive-ion APCI-MS/MS of m/z 396: 378
[MþHꢀH2O]þ (100%); positive-ion APCI-MS/MS of m/z 378: 336,
322 [MþHꢀH2OꢀC4H8]þ (100%), 264 [MþHꢀH2OꢀC4H8NCS]þ.
Negative-ion APCI-MS: m/z 394 [MꢀH]ꢀ (80%), 250 (100%); nega-
tive-ion APCI-MS/MS of m/z 394: 379 [MꢀHꢀCH3]ꢀ (100%), 295,
137. Anal. Calcd (found) for C22H25N3O2S: C 66.81 (66.62); H 6.37
(6.47); N 10.62 (10.48).
4.4.2. 3,5-Diphenyl-10-methyl-2-thioxospiro[imidazol-4,30-[3H]in-
dol]-20(10H,3H)-one (4b). Yellowish needles, mp 242–244 ꢁC (ben-
zene), Rf 0.57 (S3); IR: 3087, 3066, 3033, 2936, 1716, 1610, 1543,
1492, 1471, 1447, 1387, 1361, 1347, 1305, 1282, 1159, 1132, 1112, 1074,
1024, 949, 845, 776, 755, 685, 627, 592, 581, 539 cmꢀ1. For 1H and
13C NMR see Table 4. Positive-ion APCI-MS: m/z 384 [MþH]þ
(100%); positive-ion APCI-MS/MS of m/z 384: 326 [MþNCS]þ
(100%), 309 [MþNCS–H2O]þ, 249 [MþHꢀC6H5NCS]þ. Anal. Calcd
(found) for C23H17N3OS: C 72.04 (72.13); H 4.47 (4.58); N 10.96
(10.81).
4.4.8. (4R*,5S*)-1-Butyl-5-hydroxy-3,5-diphenyl-10-methyl-2-thioxo-
spiro[imidazolidine-4,30-[3H]indol]-20-one (5Af). Colourless plates,
mp 228–232 ꢁC (acetic acid), Rf 0.63 (S4); IR: 3420, 3059, 2959,
2933, 2872, 1699, 1613, 1496, 1469, 1449, 1367, 1290, 1230,
1196, 1136, 1112, 1054, 1009, 940, 854, 759, 741, 696, 653, 616,
540 cmꢀ1. Positive-ion APCI-MS: m/z 458 [MþH]þ (82%), 440
[MþHꢀH2O]þ (100%); positive-ion APCI-MS/MS of m/z 458: 440
[MþHꢀH2O]þ (100%); positive-ion APCI-MS/MS of m/z 440: 384
4.4.3. 10,5-Diphenyl-3-methyl-2-thioxospiro[imidazol-4,30-[3H]in-
dol]-20(10H,3H)-one (4c). Yellowish plates, mp 233–236 ꢁC (ben-
zene), Rf 0.75 (S3); IR: 3443, 3060, 3034, 2920, 1727, 1607, 1542,
1495, 1466, 1385, 1365, 1322, 1310, 1283, 1255, 1209, 1170, 1157,
1126,1104,1073,1042, 1024,1000, 979, 938, 802, 763, 703, 680, 666,
614, 585 cmꢀ1. Positive-ion APCI-MS: m/z 384 [MþH]þ (100%), 352
[MþHꢀS]þ; positive-ion APCI-MS/MS of m/z 384: 326
[MþHꢀNCS]þ (100%). Anal. Calcd (found) for C23H17N3OS: C 72.04
(72.31); H 4.47 (4.38); N 10.96 (10.71); S 8.36 (8.24).
[MþHꢀH2OꢀC4H8]þ
(100%),
325
[MþHꢀH2OꢀC4H9NCS]þ.
Negative-ion APCI-MS: m/z 456 [MꢀH]ꢀ (100%); negative-ion APCI-
MS/MS of m/z 456: 412 [MꢀHꢀC3H8]ꢀ, 357 [MꢀHꢀC4H9NCO]ꢀ
(100%), 342 [MꢀHꢀC4H8NCS]ꢀ, 137. Anal. Calcd (found) for
C27H27N3OS: C 70.87 (70.92); H 5.95 (6.01); N 9.18 (9.23).
4.4.4. 2-Thioxo-10,3,5-triphenylspiro[imidazol-4,30[3H]indol]-
20(10H,3H)-one (4d). Yellow plates, mp 204–207 ꢁC (benzene–hex-
ane), Rf 0.73 (S3); IR: 3443, 3062, 3036,1729,1608,1594,1542,1495,
1480, 1466, 1447, 1386, 1366, 1322, 1304, 1278, 1257, 1206, 1156,
1118, 1092, 1070, 1026, 1003, 984, 956, 941, 835, 813, 752,
702, 627, 616, 589, 540 cmꢀ1. Positive-ion APCI-MS: m/z 446
[MþH]þ (100%); positive-ion APCI-MS/MS of m/z 446: 413
[MþHꢀSH]þ, 388 [MþHꢀNCS]þ (100%), 371 [MþHꢀNCSꢀOH]þ,
311 [MþHꢀC6H5NCS]þ, 283. Anal. Calcd (found) for C28H19N3OS: C
75.48 (75.29); H 4.30 (4.31); N 9.43 (9.29).
4.4.9. (4R*,5R*)-1-Butyl-5-hydroxy-3,5-diphenyl-10-methyl-2-thioxo-
spiro[imidazolidine-4,30-[3H]indol]-20-one (5Bf). Colourless plates,
mp 168–170 ꢁC (benzene–hexane), Rf 0.74 (S4); IR: 3458, 3058,
2955, 2932, 2870, 1703, 1611, 1494, 1468, 1447, 1411, 1360, 1294,
1262,1187, 1135,1105, 1068, 1027, 1004, 942, 835, 785, 754, 734, 695,
663, 641, 606 cmꢀ1. Positive-ion APCI-MS: m/z 458 [MþH]þ (82%),
440 [MþHꢀH2O]þ (100%); positive-ion APCI-MS/MS of m/z 458:
440 [MþHꢀH2O]þ (100%); positive-ion APCI-MS/MS of m/z 440:
384 [MþHꢀH2OꢀC4H8]þ (100%), 325 [MþHꢀH2OꢀC4H9NCS]þ.
Negative-ion APCI-MS: m/z 456 [MꢀH]ꢀ (100%); negative-ion APCI-
MS/MS of m/z 456: 412 [MꢀHꢀC3H8]ꢀ, 357 [MꢀHꢀC4H9NCO]ꢀ
(100%), 342 [MꢀHꢀC4H8NCS]ꢀ, 137. Anal. Calcd (found) for
C27H27N3OS: C 70.87 (70.75); H 5.95 (6.04); N 9.18 (9.02).
4.4.5. (4R*,5S*)-1-Butyl-5-hydroxy-3-phenyl-10-methyl-2-thioxo-
spiro[imidazolidine-4,30-[3H]indol]-20-one (5Ab). Colourless rods,
mp 200–210 ꢁC (benzene–hexane), Rf 0.44 (S6); IR: 3457, 3342,
3184, 3061, 2933, 2832, 1702, 1607, 1492, 1470, 1418, 1372, 1309,
1249, 1150, 1121, 1089, 1074, 1017, 934, 888, 861, 839, 756, 746, 720,
697, 625, 571, 539 cmꢀ1. Positive-ion APCI-MS: m/z 402 [MþH]þ
(100%), 267 [MþHꢀC6H5NCS]þ; positive-ion APCI-MS/MS of m/z
402: 267 [MþHꢀC6H5NCS]þ (100%), 250 [MþHꢀC6H5NHCSNH2]þ.
Negative-ion APCI-MS: m/z 400 [MꢀH]ꢀ (100%); negative-ion APCI-
MS/MS of m/z 400: 281 [MꢀHꢀC6H5NCO]ꢀ (100%), 265
[MꢀHꢀC6H5NCS]ꢀ. Anal. Calcd (found) for C23H19N3O2S: C 68.81
(68.57); H 4.77 (4.59); N 10.47 (10.42).
4.4.10. (4R
*
,5S
)-1-Butyl-5-hydroxy-10,5-diphenyl-3-methyl-2-
*
thioxospiro[imidazolidine-4,30-[3H]indol]-20-one (5Ag). Colourless
needles, mp 251–253 ꢁC (ethyl acetate), Rf 0.69 (S3); IR: 3360, 3321,
3062, 2961, 2929, 2871, 1731, 1611, 1594, 1500, 1468, 1372, 1300,
1260, 1236, 1214, 1174, 1140, 1104,1061, 988, 930, 862, 764, 701, 655,
591 cmꢀ1. Positive-ion APCI-MS: m/z 458 [MþH]þ (100%), 440
[MþHꢀH2O]þ, 426, 414 [MþHꢀC3H8]þ; positive-ion APCI-MS/MS
of m/z 458: 440 [MþHꢀH2O]þ (100%), 343 [MþHꢀC4H9NCS]þ, 320
[MþHꢀC3H8ꢀC6H5ꢀOH]þ, 312, 284, 208. Negative-ion APCI-MS:
m/z 456 [MꢀH]ꢀ (100%); negative-ion APCI-MS/MS of m/z 456:
412 [MꢀHꢀC3H8]ꢀ (100%), 341 [MꢀHꢀC4H9NCS]ꢀ, 284
[MꢀHꢀ2ꢂC6H5–H2O]ꢀ. Anal. Calcd (found) for C27H27N3O2S: C
70.87 (70.81); H 5.95 (6.14); N 9.18 (9.03).
4.4.6. (4R*,5S*)-1-Butyl-10,3-dimethyl-5-hydroxy-5-phenyl-2-thioxo-
spiro[imidazolidin-4,30-[3H]indol]-20-one (5Ae). Colourless rods,
mp 227–232 ꢁC (benzene), Rf 0.59 (S3); IR: 3315, 2959, 2929,
2870, 1718, 1615, 1472, 1400, 1369, 1302, 1268, 1176, 1146, 1093,
1064, 1004, 930, 862, 755, 703, 658, 643, 596 cmꢀ1. Positive-ion
APCI-MS: m/z 396 [MþH]þ (100%), 378 [MþHꢀH2O]þ, 352
[MþHꢀC3H8]þ; positive-ion APCI-MS/MS of m/z 396: 378
4.4.11. (4R*,5R*)-1-Butyl-5-hydroxy-10,5-diphenyl-3-methyl-2-
thioxospiro[imidazolidine-4,30-[3H]indol]-20-one
(5Bg). Colourless

´
A. Klasek et al. / Tetrahedron 66 (2010) 2015–2025
2024
cubes, mp 145–149 ꢁC (cyclohexane), Rf 0.79 (S3); IR: 3378, 3059,
Negative-ion APCI-MS: m/z 350 [MꢀH]ꢀ (100%); negative-ion
APCI-MS/MS of m/z 350: 277 [MꢀHꢀCH3NCS]ꢀ, 262, 235
[MꢀHꢀC4H9NCS]ꢀ, 220 [MꢀHꢀC4H9NCSꢀCH3]ꢀ (100%). Anal.
Calcd (found) for C21H25N3S: C 71.75 (71.69); H 7.17 (7.29); N
11.95 (11.82).
2953, 2932, 2870, 1725, 1610, 1500, 1453, 1397, 1370, 1310, 1258,
1235,1200, 1180, 1106, 1054, 994, 883, 805, 753, 700, 671, 583 cmꢀ1
.
Positive-ion APCI-MS: m/z 458 [MþH]þ, 440 [MþHꢀH2O]þ (100%),
426, 414 [MþHꢀC3H8]þ; positive-ion APCI-MS/MS of m/z 458: 440
[MþHꢀH2O]þ (100%); positive-ion APCI-MS/MS of m/z 440: 384
[MþHꢀH2OꢀC4H8]þ (100%), 326 [MþHꢀH2OꢀC4H8NCS]þ, 284
[MþHꢀH2OꢀC4H9NCOꢀC4H9]þ. Negative-ion APCI-MS: m/z
456 [MꢀH]ꢀ (100%); negative-ion APCI-MS/MS of m/z 456:
4.4.16. 3-Acetamido-1,3-diphenylquinoline-2,4(1H,3H)-dione
(7d). Colourless rods, mp 280–283 ꢁC (benzene), Rf 0.13 (S3); IR:
3227, 1719, 1684, 1640, 1598, 1536, 1492, 1461, 1372, 1340, 1299, 1251,
1190,1159,1111,1071,1037,1006, 969, 853, 773, 748, 711, 664, 624, 586,
412
[MꢀHꢀC3H8]ꢀ,
339
[MꢀHꢀH2OꢀC4H9NCO]ꢀ,
284
[MꢀHꢀH2Oꢀ2ꢂC6H5]ꢀ, 282, 136. Anal. Calcd (found) for
558, 538, 513 cmꢀ1. 1H NMR (DMSO-d6):
d 1.99 (s, 3H, CH3), 6.45 (d,
C27H27N3OS: C 70.87 (71.02); H 5.95 (6.05); N 9.18 (9.00).
J¼8.2 Hz, 1H, H-8), 7.21 (m, 1H, H-6), 7.50 (br m, 7H, H-30, H-50, H-200,
H-300, H-400, H-500 and H-600), 7.58 (m, 1H, H-7), 7.62 (tt, J¼7.7 and
1.5 Hz, 1H, H-40), 7.70 (br m, 2H, H-20 and H-60), 7.85 (dd, J¼7.9 and
4.4.12. (4R
*
,5S
)-1-Butyl-5-hydroxy-10,3,5-triphenyl-2-thioxospir-
*
o[imidazolidine-4,30-[3H]indol]-20-one (5Ah). Yellow cubes, mp
154–158 ꢁC (benzene–cyclohexane), Rf 0.75 (S3); IR: 3435, 3060,
2959, 2929, 2872, 1735, 1719, 1612, 1597, 1499, 1466, 1453, 1400,
1368, 1295, 1263, 1228, 1210, 1178, 1134, 1118, 1061, 1010, 993, 939,
921, 848, 757, 738, 700, 669, 658, 609, 551, 517 cmꢀ1. Positive-ion
APCI-MS: m/z 520 [MþH]þ (75%), 502 [MþHꢀH2O]þ (100%), 488
[MþHꢀS]þ, 476 [MþHꢀC3H8]þ, 382 [MþHꢀC3H8ꢀC6H5ꢀOH]þ;
positive-ion APCI-MS/MS of m/z 520: 502 [MþHꢀH2O]þ (96%),
405 [MþHꢀC4H9NCS]þ, 387 [MþHꢀC4H9NCSꢀH2O]þ, 382
[MþHꢀC3H8ꢀC6H5ꢀOH]þ (100%). Negative-ion APCI-MS: m/z 518
[MꢀH]ꢀ (100%); negative-ion APCI-MS/MS of m/z 518: 474
[MꢀHꢀC3H8]ꢀ, 419 [MꢀHꢀC4H9NCO]ꢀ,403 [MꢀHꢀC4H9NCS]ꢀ,
399 [MꢀHꢀC6H5NCO]ꢀ, 284 [MꢀHꢀC4H9NCSꢀC6H5NCO]ꢀ (100%).
Anal. Calcd (found) for C32H29N3OS: C 73.96 (73.81); H 5.62
(5.79); N 8.09 (8.02).
1.6 Hz, 1H, H-5), 9.51 (br s, 1H, NHCO). 13C NMR (DMSO-d6):
d 21.4
(CH3), 71.8 (C-3), 116.8 (C-8), 119.7 (C-4a), 123.4 (C-6),127.5 (C-200 and
C-600),128.1 (C-40),128.9 (C-30 and C-50),129.1 (C-5),129.4 (C-300 and C-
500),129.5 (C-400),130.7 and 130.4 (C-20 and C60),132.9 (C-100),135.1 (C-
7), 137.5 (C-10), 143.0 (C-8a), 169.6 (NHCO), 170.4 (C-2), 190.1 (C-4).
Positive-ion APCI-MS: m/z 371 [MþH]þ (100%); positive-ion APCI-
MS/MS of m/z 371: 329 [MþHꢀNCO]þ (100%), 312 [MþHꢀNHCS]þ,
284. Negative-ion APCI-MS: m/z 369 [MꢀH]ꢀ (44%), 250
[MꢀHꢀC6H5NCO]ꢀ (100%), 208 [MꢀHꢀC6H5NCOꢀNCO]ꢀ; negative-
ion APCI-MS of m/z: 327 [MꢀHꢀNCO]ꢀ, 250 [MꢀHꢀC6H5NCO]ꢀ, 208
[MꢀHꢀC6H5NCOꢀNCO]ꢀ (100%). Anal. Calcd (found) for C23H18N2O3:
C 74.58 (74.74); H 4.90 (4.95); N 7.56 (7.38).
By acetylation of 1d with acetic anhydride in pyridine, com-
pound identical to 7d was prepared in 83% yield.
4.4.17. 1-Methyl-4-phenylimidazo[4,5-b]indole-2(1H,3H,4H)-thione
hydrochloride (8c$HCl). Yellowish cubes, mp 252–263 (ethanol), Rf
0.21 (S6); IR: 3274, 3134, 3057, 2967, 2908, 2804, 1642, 1594, 1573,
1502, 1446, 1420, 1365, 1330, 1304, 1283, 1221, 1192, 1121, 1023, 983,
952, 920, 817, 763, 746, 701, 645, 610, 524 cmꢀ1. 1H NMR (DMSO-
4.4.13. (4R
*
,5R
)-1-Butyl-5-hydroxy-10,3,5-triphenyl-2-thioxospir-
*
o[imidazolidine-5,30-[3H]indol]-20-one (5Bh). Colourless cubes, mp
195–199 ꢁC (benzene–hexane), Rf 0.78 (S3); IR: 3530, 3432, 3061,
2957, 2930, 2869, 1709, 1611, 1594, 1497, 1465, 1448, 1406, 1364,
1295,1264,1233,1210,1174,1116,1075,1025, 901, 789, 749, 732, 699,
664, 605, 510 cmꢀ1. Positive-ion APCI-MS: m/z 520 [MþH]þ (100%);
positive-ion APCI-MS/MS of m/z 520: 446 [MþHꢀH2OꢀC4H8]þ
(100%), 387 [MþHꢀH2OꢀNHCSꢀC4H8]þ, 295. Negative-ion APCI-
MS: m/z 518 [MꢀH]ꢀ (100%); negative-ion APCI-MS/MS of m/z 518:
474 [MꢀHꢀC3H8]ꢀ, 419 [MþHꢀC4H9NCO]ꢀ, 403 [MþHꢀC4H9NCS]ꢀ,
399 [MþHꢀC6H5NCO]ꢀ, 359, 344, 300, 284 [MþHꢀ3ꢂC6H6]ꢀ
(100%). Anal. Calcd (found) for C32H29N3OS: C 73.96 (73.87); H 5.62
(5.81); N 8.09 (7.93).
d6): d 4.11 (s, 3H, CH3), 7.38 (m, 1H, H-6), 7.42 (m, 1H, H-7), 7.58 (tt,
J¼6.9 and 1.8 Hz,1H, H-40), 7.68 (m,1H, H-5), 7.73 (m, 4H, H-20, H-30,
H-50, and H-60), 8.08 (dd, J¼7.3 and 1.6 Hz, 1H, H-8), 10.32 (br s, 2H,
protonated NH-3). 13C NMR (DMSO-d6):
d 34.7 (CH3), 111.5 (C-5),
115.9 (C-8a), 117.3 (C-8), 121.3 (C-3a), 121.8 (C-6), 122.9 (C-8b), 123.6
(C-20and C-60), 124.0 (C-7), 128.2 (C-40), 130.8 (C-30and C-50), 136.6
(C-10), 138.2 (C-4a), 166.0 (C-2). Positive-ion APCI-MS: m/z 280
[MþH]þ (100%); positive-ion APCI-MS/MS of m/z 280: 265
[MþHꢀCH3]þ, 252 [MþHꢀCO]þ (100%), 239, 224 [MþHꢀC4H8]þ.
Negative-ion APCI-MS: m/z 278 [MꢀH]ꢀ (100%); negative-ion APCI-
MS/MS of m/z 278: 263 [MꢀHꢀCH3]ꢀ (100%). Anal. Calcd (found)
for C16H14ClN3S: C 60.85 (60.67); H 4.47 (4.57); N 13.31 (13.16), S
10.15 (9.91).
4.4.14. 3-Methyl-4-(2-methylamino)phenyl-5-phenyl-1H-imidazole-
2(3H)-thione (6a). Yellowish cubes, mp 280–286 ꢁC (ethanol), Rf
0.38 (S3); IR: 3392, 3046, 2905, 2816, 2762, 1634, 1599, 1574, 1515,
1493, 1458, 1427, 1381, 1317, 1278, 1254, 1222, 1171, 1132, 1092, 1065,
1021, 961, 949, 911, 857, 836, 781, 760, 693, 681, 649, 616, 545,
530 cmꢀ1. Positive-ion APCI-MS: m/z 296 [MþH]þ (100%), 264
[MþHꢀS]þ; positive-ion APCI-MS/MS of m/z 296: 279
[MþHꢀNH3]þ, 264 [MþHꢀS]þ, 240, 237 [MþHꢀNHCS]þ, 222
[MþHꢀNHCSꢀCH3]þ, 207 [MþHꢀNHCSꢀ2ꢂCH3]þ (100%). Nega-
tive-ion APCI-MS: m/z 294 [MꢀH]ꢀ (100%); negative-ion APCI-MS/
MS of m/z 294: 279 [MꢀHꢀCH3]ꢀ (100%), 262 [MꢀHꢀS]ꢀ, 237, 220
[MþHꢀNHCSꢀCH3]þ. Anal. Calcd (found) for C17H17N3S: C 69.12
(69.01); H 5.80 (5.97); N 14.22 (14.08).
4.4.18. 3-Methyl-2-thioxo-5H,100H-spiro[imidazolidine-4,90-acri-
dine]-5-one (9c). Colourless plates, mp 298–309 ꢁC (ethyl ace-
tate–hexane), Rf 0.70 (S6); IR: 3339, 3071, 2934, 2827, 2665, 1739,
1618, 1586, 1523, 1489, 1459, 1422, 1396, 1349, 1328, 1303, 1286,
1250, 1162, 1139, 1108, 990, 969, 942, 883, 836, 763, 743, 655,
604, 568, 523 cmꢀ1. 1H NMR (DMSO-d6):
d 2.82 (s, 3H, CH3), 6.89
(dd, J¼8.0 and 1.6 Hz, 2H, H-40 and H-50), 6.98 (m, 2H, H-30 and
H-60), 7.06 (dd, J¼8.2 and 1.2 Hz, 2H, H-10 and H-80), 7.37 (m, 2H,
H-20 and H-70), 9.72 (s, 1H, H-100), 12.20 (s, 1H, H-1). 13C
NMR (DMSO-d6):
d 29.5 (CH3), 70.9 (C-4), 112.6 (C-4 and C-8b),
4.4.15. 1-Butyl-3-methyl-4-(2-(methylamino)phenyl)-5-phenyl-1H-
imidazole-2(3H)-thione (6e). Colourless cubes, mp 210–212 ꢁC
(benzene–cyclohexane), Rf 0.51 (S3); IR: 3448, 3310, 3048,
2958, 2933, 2971, 2817, 1605, 1573, 1517, 1496, 1447, 1410, 1384,
1315, 1206, 1171, 1143, 1070, 1023, 935, 764, 750, 706, 642,
523 cmꢀ1. Positive-ion APCI-MS: m/z 352 [MþH]þ (100%), 320
[MþHꢀS]þ; positive-ion APCI-MS/MS of m/z 352: 318, 296
[MþHꢀC4H8]þ (100%), 279 [MþHꢀCH3NCS]þ, 240, 207.
115.3 (C-10 and C-80), 120.7 (C-30 and C-60), 126.2 (C-40 and C-50),
130.3 (C-20and C-70), 175.0 (C-5), 180.3 (C-2). 15N NMR (DMSO-
d6):
d
¼ꢀ220.8 (1J
(
15N, 1H)¼96.6 Hz, CH3–N–C(]S)–NH–),
d
¼ꢀ233.4(CH3–N–C(]S)–NH–),
d
¼ꢀ284.9(1J (15N, 1H)¼93.9 Hz,
N–100). Positive-ion APCI-MS: m/z 296 [MþH]þ (100%); positive-
ion APCI-MS/MS of m/z 296: 265 [MþHꢀOꢀCH3]þ. Negative-ion
APCI-MS: m/z 294 [MꢀH]ꢀ (100%); negative-ion APCI-MS/MS of
m/z 294: 221 [MꢀHꢀCH3NCS]ꢀ (100%). Anal. Calcd (found) for

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A. Klasek et al. / Tetrahedron 66 (2010) 2015–2025
2025
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6. Kafka, S.; Kla´sek, A.; Polis, J.; Kosmrlj, J. Heterocycles 2002, 57, 1659.
C16H13N3OS: C 65.06 (64.84); H 4.44 (4.34); N 14.23 (13.99), S
10.86 (10.61).
7. International Tables for Crystallography; Wilson, C. A. J., Ed.; Marcel Dekker: New
York, NY, 1992; Vol C., pp 707–791.
´
ˇ
ˇ
8. Klasek, A.; Lycka, A.; Holcapek, M. Tetrahedron 2007, 63, 7059.
Acknowledgements
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9. Kla´sek, A.; Lycka, A.; Holcapek, M.; Hoza, I. Helv. Chim. Acta 2008, 91, 354.
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10. Kla´sek, A.; Koristek, K.; Lycka, A.; Holcapek, M. Tetrahedron 2003, 59, 5279.
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This study was supported by the Ministry of Education, Youth
and Sports of the Czech Republic (Grants Nos. MSM 7088352101
and VZ 0021627501) and the Czech Science Foundation (Grant No.
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