Molecular rearrangement of 9b-hydroxy-1H-imidazo[4,5-c]quinoline-2,4-diones - A convenient pathway to spiro-linked imidazolidine - oxindole derivatives

Article abstract of DOI:10.1002/hlca.200800338

The 1-substituted 3-alkyl/aryl-3-aminoquinoline-2,4(1H,3H)-diones 1 react with alkyl/aryl isocyanates to give novel 3-alkyl/aryl-3-ureidoquinoline-2,4(1H, 3H)-diones (=N-(3-alkyl/aryl-1,2,3,4-tetrahydro-2,4-dioxoquinolin-3-yl)ureas) 2 and/or 3a-alkyl/aryl

Full text of DOI:10.1002/hlca.200800338

Helvetica Chimica Acta – Vol. 92 (2009)
689
Molecular Rearrangement of 9b-Hydroxy-1H-imidazo[4,5-c]quinoline-2,4-
diones – A Convenient Pathway to Spiro-Linked Imidazolidine – Oxindole
Derivatives
by Antonꢀn Kla´sek*a), Antonꢀn Lycˇkab)c), Ivan Miksˇꢀkc)d), and Alesˇ Ru˚zicˇkae)
ˇ
a) Department of Chemistry, Faculty of Technology, Tomas Bata University, CZ-76272 Zlꢀn
(e-mail: klasek@ft.utb.cz)
b) Research Institute for Organic Syntheses (VUOS), Rybitvꢀ 296, CZ-53354 Pardubice 20
c
´
´
´
´
´
) University of Hradec Kralove, Faculty of Education, Rokitanskeho 62, CZ 50003 Hradec Kralove 3
d) Institute of Physiology of the Academy of Sciences of the Czech Republic, CZ-14220 Prague
e) Department of General and Inorganic Chemistry, Faculty of Chemical Technology, University of
Pardubice, CZ-53210 Pardubice
The 1-substituted 3-alkyl/aryl-3-aminoquinoline-2,4(1H,3H)-diones 1 react with alkyl/aryl isocya-
nates to give novel 3-alkyl/aryl-3-ureidoquinoline-2,4(1H,3H)-diones (¼ N-(3-alkyl/aryl-1,2,3,4-tetrahy-
dro-2,4-dioxoquinolin-3-yl)ureas) and/or 3a-alkyl/aryl-3,3a,5,9b-tetrahydro-9b-hydroxy-1H-imida-
2
zo[4,5-c]quinoline-2,4-diones 3 in high yields. Compounds 2 and 3 rearrange by boiling in AcOH or
concentrated HCl solution to give three different types of spiro[imidazolidine-4,3’-[3H]indole]-
2,2’(1’H)-diones, i.e., 10, 11, and 12, depending on the kind of substituents at C(3) and C(3a),
respectively. All compounds were characterized by 1H- and 13C-NMR and IR spectroscopy as well as by
atmospheric-pressure chemical-ionization (APCI) mass spectra. The structures of compounds 11c and
12Al were investigated by single-crystal X-ray diffraction analysis.
1. Introduction. – In our laboratory, much attention has been paid to study the
reactivity of 3-alkyl/aryl-3-aminoquinoline-2,4(1H,3H)-diones 1 [1 – 7]. By reacting
these a-amino ketones with nitrourea in dioxane, 3-ureidoquinolinediones 2 and/or
imidazoquinolinediones 3 have been prepared (Scheme 1; R1 ¼ R4 ¼ H) [1][2].
Compounds 2 and 3 rearrange in boiling AcOH to give, depending on the character
of substituents at positions 1 and 3, imidazoquinazolines 4 or oxindoles (¼1,3-dihydro-
2H-indol-2-ones) 5 and 6 [1][2], identical to those prepared by the reaction of 1 with
urea in boiling AcOH [3][4]. With isocyanates, compounds 1 (R1 ¼ H) afford 2 and 3
(R1 ¼ H, R4=H) [5], which rearrange in boiling AcOH to give indolylureas 7 and/or
bis[2-(imidazolyl)phenyl]ureas 9 [6][7]. Rearrangement of the same starting com-
pounds in boiling concentrated HCl produces imidazolones 8, which may be easily
transformed into 7 by heating in AcOH [7]. Owing to simple reaction protocols, the
above-mentioned transformations open an easy pathway to the preparation of new
types of heterocyclic compounds.
The reaction of 1 with isocyanates has been studied so far only with 1-unsubstituted
compounds (1; R1 ¼ H) [5 – 7]. For that reason, we set ourselves the objective of
preparing new 1,3’-disubstituted 3-ureido derivatives 2 and their cyclic isomers 3
(Scheme 1; R1, R4=H) and to study molecular rearrangements of these compounds in
ꢁ 2009 Verlag Helvetica Chimica Acta AG, Zꢂrich

690
Helvetica Chimica Acta – Vol. 92 (2009)
Scheme 1
an acid environment. We expected, by analogy to the examples presented above, the
formation of novel heterocyclic systems. Results achieved in fulfilling this task are the
object of this work.
2. Results and Discussion. – 2.1. Synthesis and Spectral Properties. By reacting 1-
alkyl/aryl-3-aminoquinoline-2,4(1H,3H)-diones 1 [8] with butyl isocyanate and phenyl
isocyanate, we prepared the corresponding 3-alkyl/arylureido derivatives 2a – 2d and
their cyclic analogues 3a,c – l (Scheme 1). The starting compounds 1 and the
isocyanates were selected in such a way as to obtain products 2 and 3 differing
mutually by the presence of aromatic (Ph) or aliphatic (Bu) substituents at positions 1
(5), 3 (3a), and 3’ (1), because the character of the substituents at these positions is
decisive for the course of the following molecular rearrangement. The presence of an

Helvetica Chimica Acta – Vol. 92 (2009)
691
H-atom or a Bu group at position 1’ (3) was chosen on the basis of our previous
experiences [1 – 7].
The results of the experiments are presented in Table 1. Compounds 2 arose only
from 3-aminoquinolinediones 1 that bear no substituent at their amino group (R3 ¼ H;
Entries 1 – 4). But, even in these cases, compounds 3 were formed as the main product –
with one exception (Entry 2). In the case of R3=H, only cyclic isomers 3 were formed
in high yields (Entries 5 – 12). These results are in accord with results published for an
analogous transformation of compounds 1 unsubstituted at position 1 (R1 ¼ H) [5].
Surprisingly, a side product of the reaction of 1c with butyl isocyanate was isolated and
identified as 3-hydroxy-1-methyl-3-phenylquinoline-2,4(1H,3H)-dione. Up to now, we
have not observed substitution of an amino group by a hydroxy group in 3-
1
aminoquinoline-2,4(1H,3H)-diones. H- and 13C-NMR spectra of compounds 2 and 3
are shown in Tables 2 and 3.
Table 1. 3-Ureidoquinoline-2,4(1H,3H)-diones
2 and 3,3a,5,9b-Tetrahydro-9b-hydroxyimidazo[4,5-
c]quinoline-2,4-diones 3 from 3-Aminoquinolinediones 1 (Scheme 1)
Entry Starting
compound
Substituents (R4 from isocyanate)
Reaction Product(s) (yield [%])
time [h]
R1
R2
R3
R4
1
2
3
4
5
6
7
8
1a
Me
Me
Me
Me
Me
Me
Me
Me
Ph
Bu
Bu
Ph
Ph
Bu
Bu
Ph
Ph
Bu
Bu
Ph
Ph
H
H
H
H
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Ph
Bu
Ph
Bu
Ph
Bu
Ph
Bu
Ph
Bu
Ph
4
3
3
1
3
2
3
2
2a (5), 3a (51)
2b (68)
1a
1c
1c
1e
1e
1g
1g
1i
2c (24), 3c (45), HQDa) (3)
2d (22), 3d (45)
3e (85)
3f (87)
3g (84)
3h (81)
3i (97)
3j (93)
3k (86)
3l (85)
9
2.5
2
3
10
11
12
1i
1k
1l
Ph
Ph
Ph
2.5
a) HQD ¼ 3-Hydroxy-1-methyl-3-phenylquinoline-2,4(1H,3H)-dione, identical to the authentic com-
pound.
Similarly to experiments performed in our earlier studies [2][6][7], we treated
compounds 2 and 3 with AcOH and concentrated HCl solution. In accord with the
proposed transformation mechanism of compounds 2 and 3 (R1 ¼ alkyl, aryl, R4 ¼ H)
[2][4], we assumed the primary rearrangement intermediate would be carbocation A
(Scheme 2). A migration of the amide group occurs in intermediate A leading to
intermediate B. The following elimination of Hþ gives rise to spiro compounds 10 in
cases where R2 is Bu (Table 4). NMR Data of compounds 10a,b,e,f,i,j are given in
Table 5, the (5E)-configuration at the exocyclic C(5)¼C bond of compounds 10 was
deduced from NOE experiments confirming spatial interaction of C(5)¼CH with the
H-atoms of the CH2(1’) and CH2(2’) groups of the N-Bu group in 10e,f,i,j (R3 ¼ Bu).
Compounds 10a,e,i are stable as crystalline materials, but they are very unstable in
(D6)DMSO solutions. Therefore, their NMR spectra were measured in CDCl3 solution
(Table 5). Unfortunately, even under these conditions, compounds 10a,e decomposed

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Helvetica Chimica Acta – Vol. 92 (2009)
Table 2. 1H- and 13C-NMR Data ((D6)DMSO) of Compounds 2a – 2d . d in ppm.
2a
2b
2c
2d
d(H)
d(C)
d(H)
d(C)
d(H)
d(C)
d(H)
d(C)
C(2)
C(3)
C(4)
C(4a)
–
–
–
–
7.91
7.25
7.76
7.42
–
172.1
67.1
193.7
120.3
127.2
122.7
136.1
115.6
142.8
157.2
–
29.8
36.8
24.7
22.1
13.7
–
–
–
–
–
7.94
7.27
7.80
7.45
–
171.6
67.4
–
–
–
–
7.86
7.23
7.76
7.46
–
171.0
71.1
–
–
–
–
7.89
7.28
7.79
7.49
–
170.4
71.2
193.3
120.1
127.4
122.9
136.4
115.8
142.7
154.6
–
29.9
36.4
24.8
22.1
13.7
–
139.8
117.7
128.7
120.1
191.3
120.0
127.8
123.0
136.3
115.9
142.4
157.6
–
191.1
119.9
127.9
123.3
136.6
116.1
142.4
154.8
–
HꢀC(5)
HꢀC(6)
HꢀC(7)
HꢀC(8)
C(8a)
N(C¼O)N
–
–
–
–
(C¼O)NHR4
Me (R1)
6.06
3.43
1.71
1.16
1.16
0.78
6.93
2.92
1.33
1.26
0.79
8.79
3.47
1.79
1.21
1.21
0.82
7.38
–
6.16
3.56
–
8.75
3.58
–
7.40
7.46
7.46
7.63
–
30.2
30.3
CH2(1’) or C(1’) (R2)
CH2(2’) or HꢀC(2’) (R2)
CH2(3’) or HꢀC(3’) (R2)
Me(4’) or HꢀC(4’) (R2)
NH (R3)
134.8
126.8
129.2
129.2
–
39.0
32.1
19.6
13.8
134.3
126.8
129.4
129.5
–
139.5
117.7
128.9
121.8
7.35
7.40
7.40
7.31
2.98
1.37
1.30
0.91
CH2(1’) or C(1’) (R4)
CH2(2’) or HꢀC(2’) (R4)
CH2(3’) or HꢀC(3’) (R4)
Me(4’) or HꢀC(4’) (R4)
40.3
32.1
19.6
13.7
7.33
7.23
6.94
7.36
7.27
6.97
Scheme 2

Helvetica Chimica Acta – Vol. 92 (2009)
693
slowly, preventing the unambiguous assignment of all NMR signals. However, the
assigned NMR signals of 10a,e in Footnote b of Table 5 were in accord with those of
compounds 10b,f,i,j.
An interesting result is that enamines 10a,b (R3 ¼ H) also arose through
rearrangement of compounds 3a and 2b (Table 4), even though, in these cases,
intermediate B bears an H-atom at N(1) capable of deprotonation and providing the
corresponding imine 11.
If substituent R2 in the starting compound is a Ph group (2c,d, 3c,d,g,h,k,l), two
different types of products arise in an acid environment. Compounds of the first type
are formed by rearrangement of 2c,d (R3 ¼ H) and 3c,d (R3 ¼ H) to give the structures
11c and 11d (Scheme 2), deducible by deprotonation of carbocation B, and assigned by
detailed NMR analysis (Table 5). The structure of 11c was confirmed by X-ray
diffraction analysis (Fig. 1). However, if the starting 3a-Ph derivatives 3g,h,k,l bear a
Bu group at position 3 (R3 ¼ Bu), carbocation B is stabilized by addition of H2O and
deprotonation, thus giving the products of the second type, i.e., spiro compounds
12g,h,k,l (Scheme 2). These structures are in accord with the occurrence of two signals
for sp3-C-atoms in their 13C-NMR spectra at d ca. 76 (C(4)) and 92 (C(5)) (Table 6),
whereas only one signal for an sp3-C-atom (C(4)) appears at d ca. 77 ppm in the
13C-NMR spectra of compounds 11c,d (Table 5).
Fig. 1. ORTEP View of compound 11c showing the thermal ellipsoids at 50% probability (arbitrary
spheres for H-atoms). Arbitrary atom numbering.
Two stereogenic centers at C(4) and C(5) are present in compounds 12. Indeed,
usually two racemates 12A and 12B were formed after rearrangement (Table 4) due to
nonstereospecific addition of H2O to carbocation B. The NMR spectra of compound
12Al obtained after rearrangement in HCl solution (Method B) show only one set of
signals, indicating that the compound in question is a pure racemic diastereoisomer

694
Helvetica Chimica Acta – Vol. 92 (2009)
Table 3. 1H- and 13C-Data ((D6)DMSO) of Compounds 3a,c – l. d in ppm.
3a
3c
3d
3e
3f
3g
d(H)
d(C) d(H)
d(C) d(H) d(C) d(H)
d(C) d(H)
d(C) d(H)
d(C)
C(2)
C(3a)
C(4)
C(5a)
–
–
–
–
7.20
7.48
7.22
7.83
–
–
6.58
3.06
159.8
65.6
171.2
137.4
114.8 7.38
130.3 7.57
123.1 7.23
127.1 7.75
123.4
85.9
–
–
–
–
–
160.0
69.2
170.6
137.6
–
–
–
–
158.5
69.7
170.4
137.4
–
–
–
–
158.6
67.9
170.6
137.1
114.5 7.18
130.2 7.37
123.1 6.96
126.6 7.33
124.0
88.0
–
–
–
–
–
157.0
68.5
170.4
136.9
114.5 7.33
130.2 7.50
122.5 7.16
127.6 7.64
123.1
85.5
–
–
–
–
–
160.2
74.3
170.0
137.4
115.1
130.5
123.2
128.0
122.3
86.5
HꢀC(6)
115.2 7.39 115.2 7.19
130.6 7.47 130.6 7.47
123.4 6.99 122.9 7.23
127.7 7.21 126.9 7.83
122.9
86.9
–
HꢀC(7)
HꢀC(8)
HꢀC(9)
C(9a)
–
–
6.41
–
–
6.92
122.2
88.5
–
–
–
6.52
–
–
7.02
–
–
6.59
C(9b)
OH
Me or
–
29.7 3.46
30.0 3.54
30.1 3.30
30.8 3.39
29.6 3.48
29.8
C(1’) (R1)
HꢀC(2’) (R1)
HꢀC(3’) (R1)
HꢀC(4’) (R1)
CH2(1’) or
C(1’) (R2)
CH2(2’) or
HꢀC(2’) (R2)
CH2(3’) or
HꢀC(3’) (R2)
Me(4’) or
HꢀC(4’) (R2)
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
1.75, 1.69 31.3
135.1
135.4 1.94, 1.88 30.8 2.04, 2.01 30.9
132.7
0.98
1.14
0.74
25.0 7.21
22.6 7.26
13.5 7.26
126.7 7.27 126.7 1.01, 0.74 24.6 1.02, 0.78 24.6 7.25
128.4
128.1
128.5
128.0 7.31 128.2 1.15
128.4 7.31 128.3 0.75
22.6 1.20
13.6 0.72
22.6 7.34
13.6 7.34
NH or CH2(1’) 7.30
–
–
–
–
7.87
–
–
–
–
8.39
–
–
–
–
3.66, 347 40.8 3.66, 3.47 41.1 3.37, 3.23 44.5
1.72, 1.61 32.5 1.72, 1.61 32.5 2.04, 1.66 31.2
1.41
0.98
CH2(2’) (R3)
CH2(3’) (R3)
Me(4’) (R3)
CH2(1’) or
–
–
–
–
–
–
–
–
–
–
20.0 1.41
14.0 0.98
20.0 1.26, 1.21 20.2
14.0 0.89 13.9
3.04, 2.86 37.4 3.14, 2.87 37.7
134.9 3.11, 2.85 37.5
–
135.6 3.01, 2.86 38.1
129.3 0.95, 0.75 30.8
127.9 0.95, 0.85 18.8
C(1’) (R4)
CH2(2’) or
0.82, 0.77 31.0 0.81
0.90, 0.75 18.9 0.90
30.8 6.92 129.5 0.77
31.0 6.88
HꢀC(2’) (R4)
CH2(3’) or
8.9 7.22 128.1 0.85, 0.75 18.9 7.23
13.5 7.20 128.4 0.57 13.5 7.20
HꢀC(3’) (R4)
Me(4’) or
0.59
13.7 0.61
126.6 0.60
13.5
HꢀC(4’) (R4)
(Table 6). The structure of 12Al was confirmed by X-ray diffraction analysis (Figs. 2
and 3). The corresponding ORTEP views indicate that the direction of the C(5) ! OH
bond in 12Al is opposite to that of the C(2’) ! O group of the indolone moiety. Hence,
it follows that the relative configuration of 12Al is (4R*,5S*). From the analysis and
mutual comparison of NMR spectra (Table 6) of the rearrangement products from
3g,h,k,l follows that also 12Ag, 12Ah, and 12Ak are pure racemic diastereoisomers with
(4R*,5S*) configuration.
Besides 12Ag,h,k,l, also 12Bg,h,k,l were isolated (Table 4). According to TLC in
several solvent systems, the corresponding pairs 12A/12B differ in their Rf values, and
the compounds are chromatographically pure. The TLC spots of compounds 12B are

Helvetica Chimica Acta – Vol. 92 (2009)
695
Table 3 (cont.)
3h
3i
3j
3k
3l
d(H)
d(C)
d(H)
d(C)
d(H)
d(C)
d(H)
d(C)
d(H)
d(C)
–
–
–
–
7.33
7.42
6.93
7.20
–
158.6
74.9
–
–
–
158.7
68.4
–
–
–
–
6.19
7.16
6.93
7.40
–
157.1
69.1
–
–
–
–
6.39
7.31
7.14
7.72
–
160.3
74.6
–
–
–
–
6.38
7.20
6.91
7.33
–
158.6
75.4
169.9
137.2
115.2
130.5
122.8
126.6
121.4
88.0
171.0
138.1
115.6
129.9
123.5
127.2
123.3
85.5
170.7
137.9
115.7
129.9
122.8
128.0
122.6
87.1
170.3
137.8
116.3
130.2
123.5
128.4
122.0
86.8
170.1
137.8
116.5
130.3
123.1
128.4
121.2
88.4
6.20
7.27
7.21
7.90
–
–
–
–
–
–
7.09
3.59
–
29.9
6.65
–
–
7.16
–
–
6.76
–
–
7.31
–
–
137.7
137.6
138.2
138.0
a
a
–
–
–
–
–
–
–
7.13
7.64
7.55
2.03, 2.00
128.7
130.3
128.4
30.8
7.22
7.65
7.57
2.12, 2.09
129.3
130.3
128.7
30.8
7.34a)
7.70
7.59
–
)
7.44a)
7.51
7.61
–
)
130.6
128.9
132.6
130.4
128.9
132.3
135.7
7.39
7.29
7.36
128.2
128.4
128.6
1.17
1.25
0.80
24.7
22.7
13.6
1.20
1.28
0.82
24.7
22.7
13.7
7.51
7.45
7.37
128.4
128.4
128.6
7.60
7.70
7.44
128.4
128.4
128.9
3.47, 3.10
2.11, 1.74
1.34, 1.25
0.92
44.8
31.0
20.3
13.9
132.7
3.50, 3.38
1.62, 1.52
1.33, 1.28
0.93
41.0
32.7
19.9
13.9
37.5
3.59, 3.46
1.72, 1.60
1.39, 1.32
0.97
41.3
32.6
20.0
14.0
135.7
3.31, 2.94
2.02, 1.66
1.26, 1.22
0.86
44.5
31.1
20.2
13.8
38.1
3.44, 3.05
2.08, 1.74
1.29, 1.21
0.89
44.8
31.0
20.2
13.8
135.9
–
3.25, 2.95
–
3.33, 2.97
–
6.96
7.23
7.19
128.7
128.1
128.8
0.85
0.92
0.66
31.1
19.0
13.4
7.06
7.26
7.06
129.3
128.1
129.0
0.0.95
1.08, 1.02
0.70
31.2
19.1
13.4
7.18
7.32
7.23
128.4
128.4
128.9
a) Broadened d(H), d(C) not observed.
yellow after exposition to I2, in contrast to those of 12A. The MS of corresponding pairs
12A/12B are almost identical, but their IR spectra are quite different. The IR
absorption bands of the C(2’) lactam group of 12B are shifted to lower wavenumbers
compared to those of 12A, which is caused by the intramolecular H-bond formation
[9]. Thus, compounds 12B are epimeric (4R*,5R*) racemates, in which an intra-
molecular H-bond occurs between C(2’)¼O and OHꢀC(5). However, the NMR data
of compounds 12B were surprising. The composition of the solutions of these
compounds in (D6)DMSO was not constant but changed with time. For instance,
immediately after dissolution, the chromatographically pure 12Bg showed NMR

696
Helvetica Chimica Acta – Vol. 92 (2009)
Table 4. Molecular Rearrangement of Compounds 2 and 3 in Boiling AcOH (Method A) and
Concentrated HCl Solution (Method B) (Scheme 2)a)
Entry
Starting compound
Method
Reaction time [h]
Product(s) (yield [%])
1
2
3
4
5
6
7
8
3a
3a
2b
2b
2c
2c
3c
3c
2d
2d
3d
3d
3e
3e
3f
3f
3g
3g
3h
3h
3i
A
B
A
B
A
B
A
B
A
B
A
B
A
B
A
B
A
B
A
B
A
B
A
B
A
B
A
B
1.5
1.5
2
2
1
0.5
1
1.5
2
0.5
2.5
0.5
2
1
1
1
3
1
3
2
1
10a (38)
10a (6), MeIsb) (6)
10b (9)
10b (40)
11c (92)
11c (90)
11c (91)
11c (37)
11d (41)
11d (45)
11d (38)
11d (53)
10e (79)
10e (77)
10f (83)
10f (52)
12Ag (33), 12Bg (46)
12Ag (51)
12Ah (33), 12Bh (37)
12Ah (83)
10i (81)
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
3i
3j
3j
3k
3k
3l
0.5
1
0.5
6
4
3
10i (72)
10j (84)
10j (84)
12Ak (47), 12Bk (11)
12Ak (31), 12Bk (24)
12Al (42), 12Bl (19)
12Al (80)
3l
2
a) For substituents, see Scheme 1. b) MeIs ¼ N-Methylisatin (¼ 1-methyl-1H-indole-2,3-dione), identical
to authentic compound (Aldrich, Cat. No. 183075).
signals indicating the presence of ca. 40% of 12Ag. In the course of time, the (4R*,5S*)
diastereoisomer 12Ag started to dominate and, after 30 h, the solution contained ca.
80% of 12Ag. A similar behavior was observed in the case of 12Bh; the starting content
of ca. 50% of the (4R*,5R*) diastereoisomer 12Bh in the mixture with 12Ah diminished
with time to ca. 15%. Though, we were able to assign most of the signals of (4R*,5R*)
diastereoisomer 12Bg and also some signals of the (4R*,5R*) diasteroisomer 12Bh
1
(Table 6). The differences between the H-NMR spectra of epimeric racemates 12A
and 12B (Table 6) are probably due to the ring-current effect of the Ph group and H-
bonding.
The solutions of compounds 12Bk and 12Bl in (D6)DMSO exhibited, according to
1H-NMR, only a small content (ca. 5%) of (4R*,5R*) diastereoisomers, and no signals
of these compounds could be found in the 13C-NMR spectra. However, from TLC we
have arguments for diastereoisomer purity of 12Bk and 12Bl in the crystalline state. It

Helvetica Chimica Acta – Vol. 92 (2009)
697
Table 5. 1H- and 13C-NMR Data ((D6)DMSO) of Compounds 10a) and 11. d in ppm.
Position
10b
10f
10ib)
10j
11c
11d
d(C) d(H) d(C)
d(H) d(C) d(H)
d(C) d(H)
d(C)
d(H)
d(C) d(H)
C(2)
C(4)
C(5)
C(2’)
–
–
–
–
–
156.9
70.9
135.2
173.2
127.7
–
–
–
–
–
155.5
68.8
135.0
172.2
126.5
124.7 7.33
123.7 7.22
130.8 7.39
109.5 6.94
143.8
26.6
–
–
–
–
–
157.7
67.8
–
–
–
–
155.5
69.0
134.9
171.7
126.5
125.4 7.29
124.5 7.17
130.9 7.60
109.8 7.41
–
–
–
–
–
166.2
76.2
181.3
169.7
122.8
125.0 7.28 125.1
124.2 7.13 124.2
131.8 7.52 131.7
111.0 7.48 110.7
–
–
–
–
–
164.7
77.8
181.5
169.3
122.6
136.2
172.7
126.8
125.3
124.1
130.2
109.9
143.9
134.0
C(3a’)
–
HꢀC(4’)
7.39 124.4 7.40
7.11 123.6 7.14
7.41 130.4 7.41
7.11 109.6 7.09
–
3.19
7.53
7.23
7.38
6.74
–
HꢀC(5’)
HꢀC(6’)
HꢀC(7’)
C(7a’)
143.8
26.7 3.17
–
–
–
143.5
133.4 3.39
–
144.0
29.9 3.32
–
143.7
27.20
Me of
–
C(1’) (R1)
HꢀC(2’) (R1)
HꢀC(3’) (R1)
HꢀC(4’) (R1)
HꢀC(1’) or
C(1’) (R2)
CH2(2’) or
HꢀC(2’) (R2)
CH2(3’) or
HꢀC(3’) (R2)
Me(4’) or
HꢀC(4’) (R2)
NH or
–
–
–
3.78
–
–
–
–
–
–
–
–
–
7.47
7.63
7.52
126.0
129.8
128.4
99.7
7.18
7.63
7.55
4.82
126.6
130.2
128.9
100.2
–
–
–
–
–
–
–
–
–
–
–
–
–
–
97.3 4.70
99.8 4.61
128.8
128.7
1.97
1.24
0.80
9.99
27.2 1.43, 1.26 26.7 1.68, 1.46 27.6, – 1.62, 1.46 27.3 7.56
22.3 1.07, 0.96 22.5 1.17, 1.05 23.1 1.11, 1.02 22.6 7.47
13.3 0.56 13.5 0.68 13.5 0.61 13.5 7.62
3.63, 3.61 39.7 3.53, 3.50 40.4 3.64, 3.61 39.8
128.0 7.62 128.0
129.6 7.50 129.5
134.0 7.66 134.1
–
–
–
–
–
CH2(1’) (R3)
CH2(2’) (R3)
CH2(3’) (R3)
Me(4’) (R3)
C(1’) or
–
–
–
–
–
–
1.62
1.44
0.99
–
28.1 1.63
19.4 1.48
13.9 0.88
28.5
19.9
13.5
1.65
1.44
1.00
–
28.1
19.4
13.9
–
–
–
–
–
–
–
–
–
–
–
–
–
136.6
135.8 3.16, 2.95 41.0
135.7 3.15, 3.04 40.2
134.5
CH2(1’) (R4)
HꢀC(2’) or
CH2(2’) (R4)
HꢀC(3’) or
CH2(3’) (R4)
HꢀC(4’) or
Me(4’) (R4)
7.06 124.1 6.94
7.23 128.8 7.24
7.09 125.5 7.16
126.2 1.45
128.9 1.30
126.7 1.05
28.5
19.9
13.8
7.01
7.31
7.23
126.0 1.20
129.0 1.20
127.0 0.76
29.9 7.11 125.6
19.2 7.35 129.2
13.4 7.27 127.5
a) Due to instability of 10a and 10e solutions, we were not able to assign NMR signals unambigously. The
following signals (in CDCl3) were assigned: 10a: d(H) 3.33 (Me (R1)) and 3.87 (HꢀC(1’) (R2)); d(C) 70.4
(C(4)), 174.0 (C(2’)), 144.1 (C(7a’)), 26.7 (Me (R1)), and 98.7 (CH(1’) (R2)). 10e: d(H) 3.23 (Me (R1)) and
4.54 (HꢀC(1’) (R2)); d(C) 157.1 (C(2)), 70.2 (C(4)), 173.3 (C(2’)), 143.8 (C(7a’)), 27.2 (Me (R1)), and 99.6
(CH(1’) (R2)). b) Measured in CDCl3.
is plausible that compounds 12B epimerize to 12A in (D6)DMSO solution via the
opening and subsequent closing of the imidazoline ring.
The comparison of the rearrangement results obtained by Method A and Method B
(Table 4) shows that it is generally impossible to decide which one provides better
yields (see, e.g., Entries 25 – 28). In case of compounds 3g,h,l, it is worth mentioning
that only the more stable racemates 12Ag,h,l were obtained by Method B. Therefore,

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Helvetica Chimica Acta – Vol. 92 (2009)
Table 6. 1H- and 13C-NMR Data ((D6)DMSO) of Compounds 12. d in ppm.
12Ag
12Bg
12Ah
12Bh
12Ak
12Al
d(H)
d(C) d(H) d(C) d(H)
d(C) d(H)
d(C) d(H)
d(C) d(H)
d(C)
C(2)
C(4)
C(5)
C(2’)
–
–
–
–
161.6
75.8
91.4
173.8
121.7
–
–
–
–
–
160.0
74.8
93.0
174.0
121.0
–
–
–
–
–
159.3
76.4
91.5
173.2
121.3
128.4 5.63
121.9 6.46
130.2 7.24
108.3 6.96
–
–
–
–
–
157.5
75.5
93.4
173.4
121.2
125.5 7.82
122.8 7.24
129.9 7.38
108.6 6.51
–
–
–
–
–
161.5
75.6
91.7
173.5
121.3
129.0 7.72
122.4 7.14
130.4 7.34
108.6 6.49
–
–
–
–
–
159.2
76.1
91.6
172.8
121.0
127.6
122.6
130.4
108.7
143.9
–
C(3’a)
–
HꢀC(4’)
HꢀC(5’)
HꢀC(6’)
HꢀC(7’)
C(7’a)
7.71
7.17
7.41
6.85
–
128.4 5.67 125.8 7.64
121.6 6.57 123.0 7.10
130.2 7.26 129.9 7.36
108.2 6.98 108.5 6.82
144.4
–
–
6.80
145.0
–
–
7.28
144.1
–
25.6 3.21
–
144.6
–
26.5
–
7.07
–
144.2
–
133.4
–
7.06
–
a
OH
Me or
6.91
2.54
)
25.5 3.18 26.3 2.53
133.2
C(1’) (R1)
HꢀC(2’) (R1)
HꢀC(3’) (R1)
HꢀC(4’) (R1)
C(1’) (R2)
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
7.03
7.26
7.32
–
–
–
–
–
–
–
–
–
–
6.52
7.43
7.36
–
7.08
7.31
7.33
126.2 6.53
129.5 7.43
128.3 7.35
126.1
129.6
128.4
135.6
127.8
127.6
128.8
a
136.1
127.3
127.1
128.4
139.1
135.3
127.4
127.2
128.7
)
)
)
)
136.3
127.7
127.5
128.6
–
a
a
a
a
b
HꢀC(2’) (R2) 6.99
HꢀC(3’) (R2) 7.21
HꢀC(4’) (R2) 7.28
)
)
)
)
)
)
)
)
)
)
)
)
)
)
)
)
)
a
a
a
a
a
a
a
a
a
a
a
b
b
a
a
CH2(1’) (R3) 3.10, 3.01 42.0
CH2(2’) (R3) 1.86, 1.71 31.2
40.5 3.22, 3.12 42.0 3.49, 2.86 40.7 3.12, 3.04 41.8 3.25, 3.16 42.1
31.7 1.91, 1.80 31.2 1.63 31.5 1.89, 1.78 31.2 1.95, 1.84 31.0
19.8 1.33
13.9 0.93
CH2(3’) (R3) 1.29
20.2
13.9
20.2 1.37
13.9 0.93
19.8 1.32
13.9 0.92
20.3 1.34
13.7 0.94
–
20.2
13.9
137.4
Me(4’) (R3)
CH2(1’) or
0.91
3.16, 2.68 41.8
a
a
41.7
–
137.5
124.2
128.5
124.9
)
)
)
)
)
)
)
)
3.19, 2.93 41.8
C(1’) (R4)
a
a
a
a
a
a
a
a
a
b
CH2(2’) or
1.18
1.18
0.74
30.7
19.4
13.6
)
)
)
30.8 7.06
19.3 7.21
13.6 7.06
1.20
1.20
0.78
30.8
19.5
13.7
)
)
)
123.9
128.6
124.9
HꢀC(2’) (R4)
b
b
CH2(3’) or
HꢀC(3’) (R4)
Me (4’) or
HꢀC(4’) (R4)
a) Due to instability of 12Bg and 12Bh solutions, we were not able to assign NMR signals unambigously.
b) Strong overlap of signals, the assignment would be uncertain.
we treated pure compounds 12Bg,h,k,l in a boiling mixture of HCl and AcOH and
actually obtained pure compounds 12Ag,h,k,l in moderate yields; the existence of a
mixture 12A/12B in the mother liquors was evidenced by TLC. Under the same
reaction conditions, pure compounds 12Ayielded mixtures 12A/12B, i.e., the reaction is
reversible and the equilibrium between both components depends on the solvent. In
DMSO, the equilibrium is shifted to compounds 12A, which causes problems during
NMR spectra measuring. In CDCl3, compounds 12B are only slightly soluble.
2.2. Solid-State Structures. Both compounds 11c and 12Al crystallize in the triclinic
space group P1, but the unit cell for 12Al contains two geometrically independent
molecules. Relevant crystallographic details for both compounds are given in Table 7.
Although there are many structures of spiro-indole derivatives determined by X-ray

Helvetica Chimica Acta – Vol. 92 (2009)
699
Table 7. Crystallographic Data of 11c and 12Al
11c
12Al · 0.5 acetone
Empirical formula
C21H21N3O2
triclinic
P1
9.0351(7)
10.1110(8)
10.9844(13)
83.026(7)
77.807(7)
65.868(6)
2
C33H26N3O3
triclinic
P1
13.4822(10)
14.4551(9)
14.8441(12)
85.294(6)
80.916(6)
71.245(6)
4
Crystal system
Space group
a [ꢃ]
b [ꢃ]
c [ꢃ]
a [8]
b [8]
g [8]
Z
V [ꢃ3]
894.38(14)
1.290
2703.4(3)
1.380
Dc [g cmꢀ3
]
Crystal size [mm]
Crystal shape
0.512 ꢁ 0.132 ꢁ 0.122
colorless block
0.085
0.32 ꢁ 0.28 ꢁ 0.19
colorless block
0.091
m [mmꢀ1
F (000)
]
368
1192
h; k; l (range)
q range [8]
ꢀ 10, 11; ꢀ 12, 13; ꢀ 14, 14
2.97; 27.5
14849
4042 (0.0786)
2671
ꢀ 17, 17; ꢀ 18, 18; ꢀ 19, 19
2.07; 27.5
48211
Reflections measured
independent (Rint)a)
observed (I > 2s (I))
Parameters refined
Max., min. D1/e [ꢃꢀ3
G.o.f. b)
Rc) wRc)
12232 (0.1043)
8610
686
235
]
0.456, ꢀ 0.485
0.626, ꢀ 0.611
1.063
0.811
0.0725, 0.1521
0.0949, 0.2592
b
a) Rint ¼ S j Fo2 ꢀ Fo2;mean j /SFo2. ) G.o.f. ¼ [S(w(Fo2 ꢀ Fc2 )2)/(Ndiffrs ꢀ Nparams)]1/2 for all data. c) R(F) ¼
S jj Fo jꢀ Fc jj /S j Fo j for observed data, wR(F2) ¼ [S(w(Fo2 ꢀ Fc2 )2)/(Sw(F2o )2)]1/2 for all data.
techniques, these compounds are the first examples of spiro[imidazolidine-4,3’-
oxindoles]. The ORTEP views of 11c and 12Al (Figs. 1 and 2) show an almost planar
arrangement of each five-membered ring with interplanar angles being 88.3(2)8 for 11c
and 89.3(2) and 85.9(1)8 for 12Al. The C(2)ꢀN(2) distance (1.283(3) ꢃ) in compound
11c reveals a typical double-bond character with respect to the standard single-bond
N(sp3)ꢀC(sp2) distance of 1.44 ꢃ [10] (atom numbering of Fig. 1). Both C(1)ꢀO(1)
and C(4)ꢀO(2) distances and the geometry of the respective groups are characteristic
for C¼O groups. On the other hand, in 12Al, O(3)ꢀC(2) (1.402(4) ꢃ) and
O(3’)ꢀC(2’) (1.398(4) ꢃ) are single bonds (atom numberings of Figs. 2 and 3). The
classical H-bonding patterns operate through these groups (O(3’)ꢀH(3’)ꢀO(1) 169.78,
O(3’)ꢀO(1) 2.710(3) ꢃ) in the structure of 12Al (Fig. 3). There is also an additional
p – p stacking interaction between almost coplanar Ph rings in the crystal unit cell
(distance 3.568 ꢃ).
3. Conclusions. – The elaborated methods allow to prepare spiro-oxindoles 10 – 12
from 3-aminoquinolinediones 1 in good to very good yields. The molecular rearrange-
ment of compounds 2 and 3 is not only of theoretical importance but enables, through a

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Helvetica Chimica Acta – Vol. 92 (2009)
Fig. 2. ORTEP View of one of two independent molecules of compound 12Al showing the thermal
ellipsoids at 50% probability (arbitrary spheres for H-atoms). Arbitrary atom numbering:
C(2)ꢀC(3)ꢀH corresponds to C(5)ꢀOH and C(4)ꢀC(2) to C(2’)¼O in Scheme 2.
simple procedure, a targeted preparation of new types of spiro-oxindoles suitable both
for biological testing as well as for studying further transformations. Spiro[imidazo-
lidine-4,3’-oxindoles] have not been described so far, except for two compounds of type
5 mentioned in our earlier reports [2][4]. One of these compounds, bearing a Ph group
at position 1’, exhibits high toxicity against K-562 (chronic myeloid leukemia) and
MCF 7 (breast carcinoma) [2]. The presented work extends the set of compounds
containing a spiro-oxindole structural motif which is a component in some indole
alkaloids [11] as well as in other compounds presumed to display significant biological
activities [12][13].
This study was supported by the Ministry of Education, Youth, and Sports of the Czech Republic
(Grants No. MSM 7088352101 and MSM 0021627501) and the Czech Science Foundation (Grant No. 203/
´
07/0320). The authors thank Dr. Robert Vꢀcha for MS data of compounds 2a and 2c and Mrs. H. Gerzˇova
for technical help (both Faculty of Technology, Tomas Bata University, Zlꢀn).

Helvetica Chimica Acta – Vol. 92 (2009)
701
Fig. 3. View of hydrogen bridging in 12Al. Arbitrary atom numbering: C(2)ꢀC(3)ꢀH corresponds to
C(5)ꢀOH and C(4)ꢀC(2) to C(2’)¼O in Scheme 2.
Experimental Part
1. General. TLC: Alugramꢄ-SIL-G/UV254 foils (Macherey – Nagel); elution with benzene/AcOEt
4 :1, CHCl3/EtOH 9 :1 and/or 19 :1), and CHCl3/AcOEt 7:3. Column chromatography (CC): silica gel
(SiO2; Merck, grade 60, 70 – 230 mesh); elution with CHCl3, then CHCl3/EtOH 99 :1 ! 8 :2 or benzene,
and then benzene/AcOEt 99 :1 ! 8 :2. M.p.: Kofler block or Gallencamp apparatus. IR Spectra: Mattson-
3000 spectrophotometer; KBr pellets; ˜n in cmꢀ1. NMR Spectra: Bruker Avance-500 spectrometer at
500.13 MHz (1H) and 125.76 MHz (13C); (D6)DMSO or CDCl3 solns.; d in ppm rel. to Me4Si as internal
standard, J in Hz; manufacturerꢅs software for all 2D experiments (gradient-selected (gs)-COSY, gs-
NOESY, gs-TOCSY, gs-HMQC, and gs-HMBC); d(H) assignments by gs-COSY and gs-TOCSY; d(C)
assignments of protonated C-atoms by gs-HMQC and of quaternary C-atoms by gs-HMBC.
Atmospheric-pressure chemical-ionization (APCI) MS: positive- and negative-ion mode with an ion-
trap analyzer Agilent LC-MSD Trap XCT-Ultra (Agilent, Palo Alto, CA, USA) within m/z 50 – 500;
analysis of samples in MeCN by direct infusion (10 ml) at the flow rate of 400 ml/min; ion-source temp.
3508, APCI-probe temp. 3508, flow rate and N2 pressure 4 l/min and 45 psi, resp.; MS/MS: isolation width
of precursor ions 4 m/z and collision amplitude 0.8 V; the MS of 2a and 2c were measured with an MS-
Trio-1000-Fisons instrument within m/z 50 – 500, ion source 2008, 70 eV. Elemental analyses (C, H, N):
EA-1108 elemental analyzer (Fisons Instrument).
2. X-Ray Analysis. The X-ray data for colorless crystals of 11c and 12Al (grown from ca. 5% Et2O
and acetone) were obtained at 1508 K with an Oxford-Cryostream low-temperature device and a Nonius-
KappaCCD diffractometer with MoKa radiation (l 0.71073 ꢃ), a graphite monochromator, and the f
and c scan mode. Data reductions were performed with DENZO-SMN [14]. The absorption was
corrected by integration methods [15]. Structures were solved by direct methods (Sir92) [16] and refined
by full-matrix least squares based on F2 (SHELXL97) [17]. H-Atoms were mostly localized on a
difference Fourier map; however, to ensure uniformity of treatment of the crystal (form), all H-atoms
were recalculated into idealized positions (riding model) and assigned temp. factors Hiso(H) ¼ 1.2 Ueq
(pivot atom) or 1.5 Ueq for CꢀH ¼ 0.96, 0.97, and 0.93 ꢃ of Me, CH2, and H-atoms at aromatic rings,
resp., and for OꢀH ¼ 0.82 ꢃ of the OH group. There is disordered solvent (acetone) in the structure of
12Al. Attempts to model this disorder or split it into two positions were unsuccessful. PLATON/

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Helvetica Chimica Acta – Vol. 92 (2009)
SQUEZZE [18] was used to correct the data for the presence of disordered solvent. A potential solvent
volume of 188 ꢃ3 was found. Per unit cell, 61 electrons worth of scattering were located in the void. The
calculated stoichiometry of solvent was calculated to be two molecules of acetone per unit cell which
results in 64 electrons per unit cell1).
3. 3-Aminoquinoline-2,4(1H,3H)-diones 1 were prepared from the corresponding 3-chloroquinoline-
2,4(1H,3H)-diones according to the protocol described in [8].
4. 3-Ureidoquinoline-2,4(1H,3H)-diones 2 and 3,3a,5,9b-Tetrahydro-9b-hydroxy-1H-imidazo[4,5-
c]quinoline-2,4-diones 3: General Procedure. Phenyl isocyanate (0.130 ml, 1.2 mmol) or butyl isocyanate
(0.135 ml, 1.2 mmol) was added to the cooled (08) and stirred soln. of 1 (1 mmol) in CHCl3 (5 ml). After
stirring at r.t. for the time given in Table 1, the precipitate was collected by filtration with suction and
recrystallized from an appropriate solvent. In cases of mixtures 2/3, these were separated by repeated
fractional crystallization or by CC. When the product was soluble in CHCl3, the soln. was concentrated,
and the residue was crystallized from an appropriate solvent. In some cases, the mother liquors were
worked up by CC (SiO2). Yields of 2 and 3 are given in Table 1.
3-Butyl-3-(3’-butylureido)-1-methylquinoline-2,4(1H,3H)-dione (¼ N-Butyl-N’-(3-butyl-1,2,3,4-tet-
rahydro-1-methyl-2,4-dioxoquinolin-3-yl)urea; 2a). Prepared from 1a (besides 3a). Colorless crystals.
M.p. 152 – 1578 (benzene/hexane). IR: 3374, 3146, 3087, 2958, 2931, 2871, 1703, 1665, 1628, 1602, 1565,
1474, 1361, 1301, 1280, 1227, 1146, 1114, 1089, 1018, 945, 761, 731, 655, 603, 560, 521. 1H- and 13C-NMR:
Table 2. EI-MS: 345 (5, Mþ), 327 (98), 298 (85), 256 (78), 244 (95), 216 (83), 200 (79), 187 (100), 160
(51), 131 (41), 104 (22), 89 (13), 77 (19), 57 (16), 55 (22). Anal. calc. for C19H27N3O3 (345.44): C 66.06, H
7.88, N 12.16; found: C 66.22, H 7.92, N 12.31.
3-Butyl-1-methyl-3-(3’-phenylureido)quinoline-2,4(1H,3H)-dione (¼ N-(3-Butyl-1,2,3,4-tetrahydro-
1-methyl-2,4-dioxoquinolin-3-yl)-N’-phenylurea; 2b). Prepared from 1b. Colorless crystals. M.p. 195 –
2008 (AcOEt/hexane). IR: 3347, 3145, 3094, 3027, 2954, 2926, 2868, 1674, 1652, 1600, 1553, 1498, 1474,
1441, 1373, 1363, 1315, 1185, 1119, 1083, 1049, 1014, 951, 896, 849, 752, 691, 660, 582, 504. 1H- and
13C-NMR: Table 2. APCI-MS (pos.): 366 (100, [M þ H]þ), 247 (59, [M þ H ꢀ C6H5NCO]þ). APCI-MS/
MS (pos.) of 366: 247 (100, [M þ H ꢀ C6H5NCO]þ), 230 (15, [M þ H ꢀ C6H5NHCO ꢀ NH2]þ). APCI-
MS (neg.): 364 (100, [M ꢀ H]ꢀ). APCI-MS/MS (neg.) of 364: 245 (100, [M ꢀ H ꢀ C6H5NCO]ꢀ), 188 (14,
[M ꢀ H ꢀ C6H5NCO ꢀ C4H9]ꢀ). Anal. calc. for C21H23N3O3 (365.43): C 69.02, H 6.34, N 11.50; found: C
69.14, H 6.42, N 11.39.
3-(3’-Butylureido)-1-methyl-3-phenylquinoline-2,4(1H,3H)-dione (¼ N-Butyl-N’-(1,2,3,4-tetrahydro-
1-methyl-2,4-dioxo-3-phenylquinolin-3-yl)urea; 2c). Prepared from 1c (besides 3c and 3-hydroxy-1-
methyl-3-phenylquinoline-2,4(1H,3H)-dione). Colorless crystals. M.p. 186 – 1908 (benzene). IR: 3382,
3061, 2957, 2931, 2869, 1707, 1667, 1626, 1601, 1557, 1472, 1418, 1356, 1302, 1275, 1257, 1204, 1171, 1135,
1
1059, 1038, 870, 770, 697, 660, 581, 562, 528. H- and 13C-NMR: Table 2. EI-MS: (3, Mþ), 348 (12), 276
(5), 244 (100), 216 (42), 188 (14), 187 (50), 160 (32), 132 (12), 131 (21), 117 (6), 104 (17), 103 (9), 77
(14), 57 (5). Anal. calc. for C21H23N3O3 (365.43): C 69.02, H 6.34, N 11.50; found: C 69.17, H 6.48, N 11.28.
1-Methyl-3-phenyl-3-(3’-phenylureido)quinoline-2,4(1H,3H)-dione (¼ N-Phenyl-N’-(1,2,3,4-tetrahy-
dro-1-methyl-2,4-dioxo-3-phenylquinolin-3-yl)urea; 2d). Prepared from 1d (besides 3d). Colorless
crystals. M.p. 218 – 2228 (EtOH). IR: 3373, 3335, 3209, 3148, 3086, 3062, 1705, 1680, 1649, 1599, 1554,
1495, 1474, 1417, 1368, 1314, 1246, 1227, 1190, 1175, 1126, 1061, 1032, 953, 888, 868, 848, 766, 746, 687, 660,
640, 574, 531, 505. 1H- and 13C-NMR: Table 2. APCI-MS (pos.): 386 (100, [M þ H]þ), 267 (38, [M þ H ꢀ
C6H5NCO]þ). APCI-MS/MS (pos.) of 386: 267 (100, [M þ H ꢀ C6H5NCO]þ), 250 (11, [M þ H ꢀ
C6H5NHCO ꢀ NH2]þ). APCI-MS (neg.): 384 (100, [M ꢀ H]ꢀ), 265 (18, [M ꢀ H ꢀ C6H5NCO]ꢀ), 250
(80, [M ꢀ H ꢀ C6H5NCO ꢀ CH3]ꢀ). APCI-MS/MS (neg.) of 384: 265 (100, [M ꢀ H ꢀ C6H5NCO]ꢀ), 208
(21). Anal. calc. for C23H19N3O3 (385.42): C 71.67, H 4.97, N 10.90; found: C 71.35, H 5.13, N 10.76.
1,3a-Dibutyl-3,3a,5,9b-tetrahydro-9b-hydroxy-5-methyl-1H-imidazo[4,5-c]quinoline-2,4-dione (3a).
Prepared from 1a (besides 2a). Colorless crystals. M.p. 162 – 1678 (AcOEt/hexane). IR: 3268, 2957, 2931,
2870, 1704, 1690, 1656, 1605, 1476, 1449, 1415, 1366, 1315, 1267, 1223, 1170, 1115, 1079, 1051, 1030, 992,
1
)
CCDC-684114 and 684115 for 11c and 12Al, resp., 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.

Helvetica Chimica Acta – Vol. 92 (2009)
703
949, 937, 767, 739, 654, 609, 579, 546. 1H- and 13C-NMR: Table 3. APCI-MS (pos.): 346 (100, [M þ H]þ),
328 (27, [M þ H ꢀ H2O]þ), 302 (23, [M þ H ꢀ C3H8]þ), 247 (38, [M þ H ꢀ C4H9NCO]þ). APCI-MS/MS
(pos.) of 346: 247 (100, [M þ H ꢀ C4H9NCO]þ). APCI-MS (neg.): 344 (100, [M ꢀ H]ꢀ), 326 (4, [M ꢀ
H ꢀ H2O]ꢀ), 245 (3, [M ꢀ H ꢀ C4H9NCO]ꢀ). APCI-MS/MS (neg.) of 344: 245 (100, [M ꢀ H ꢀ
C4H9NCO]ꢀ), 211 (23), 188 (8, [M ꢀ H ꢀ C4H9NCO ꢀ C4H9]ꢀ). Anal. calc. for C19H27N3O3 (345.44): C
66.06, H 7.88, N 13.89; found: C 66.19, H 7.99, N 13.62.
1-Butyl-3,3a,5,9b-tetrahydro-9b-hydroxy-5-methyl-3a-phenyl-1H-imidazo[4,5-c]quinoline-2,4-dione
(3c). Prepared from 1c (besides 2c and 3-hydroxy-1-methyl-3-phenylquinoline-2,4(1H,3H)-dione).
Colorless crystals. M.p. 175 – 1778 (benzene). IR: 3285, 3067, 3032, 2953, 2931, 2868, 1712, 1699, 1674,
1658, 1604, 1474, 1408, 1374, 1304, 1267, 1230, 2934, 2870, 1692, 1664, 1602, 1500, 1470, 1417, 1371, 1356,
1300, 1264, 1238, 1206, 1173, 1137, 1114, 1094, 1054, 1019, 966, 913, 880, 855, 760, 738, 704, 691, 679, 664,
652, 604, 557, 540, 505. 1H- and 13C-NMR: Table 3. APCI-MS (pos.): 366 (100, [M þ H]þ), 348 (34, [M þ
H ꢀ H2O]þ), 267 (78, [M þ H ꢀ C4H9NCO]þ). APCI-MS/MS (pos.) of 366: 267 (100, [M þ H ꢀ
C4H9NCO]þ). APCI-MS (neg.): 364 (100, [M ꢀ H]ꢀ), 265 (9, [M ꢀ H ꢀ C4H9NCO]ꢀ). APCI-MS/MS
(neg.) of 364: 265 (100, [M ꢀ H ꢀ C4H9NCO]ꢀ), 245 (8, [M ꢀ H ꢀ C6H5NCO]ꢀ), 231 (8, [M ꢀ H ꢀ
C6H5 ꢀ C4H8]ꢀ), 208 (5). Anal. calc. for C21H23N3O3 (365.43): C 69.02, H 6.34, N 11.50; found: C 69.10, H
6.38, N 11.35.
3,3a,5,9b-Tetrahydro-9b-hydroxy-5-methyl-1,3a-diphenyl-1H-imidazo[4,5-c]quinoline-2,4-dione
(3d). Prepared from 1d (besides 2d). Colorless crystals. M.p. 188 – 1928 (EtOH). IR: 3386, 3284, 3086,
3063, 2942, 1711, 1669, 1657, 1604, 1497, 1472, 1384, 1300, 1271, 1224, 1148, 1131, 1110, 1052, 992, 933, 859,
1
833, 756, 697, 655, 631, 554, 532. H- and 13C-NMR: Table 3. APCI-MS (pos.): 386 (64, [M þ H]þ), 368
(12, [M þ H ꢀ H2O]þ), 267 (100, [M þ H ꢀ C6H5NCO]þ). APCI-MS/MS (pos.) of 386: 267 (100, [M þ
H ꢀ C6H5NCO]þ), 250 (11, [M þ H ꢀ C6H5NHCO ꢀ NH2]þ). APCI-MS (neg.): 384 (67, [M ꢀ H]ꢀ), 265
(8, [M ꢀ H ꢀ C6H5NCO]ꢀ), 250 (100, [M ꢀ H ꢀ C6H5NCO ꢀ CH3]ꢀ). APCI-MS/MS (neg.) of 384: 265
(100, [M ꢀ H ꢀ C6H5NCO]ꢀ), 208 (4). Anal. calc. for C23H19N3O3 (385.42): C 71.67, H 4.97, N 10.90;
found: C 71.50, H 4.89, N 10.81.
1,3,3a-Tributyl-3,3a,5,9b-tetrahydro-9b-hydroxy-5-methyl-1H-imidazo[4,5-c]quinoline-2,4-dione
(3e). Prepared from 1e. Colorless crystals. M.p. 117 – 1208 (hexane). IR: 3319, 3086, 3052, 2957, 2931,
2871, 1694, 1669, 1604, 1501, 1470, 1420, 1369, 1312, 1267, 1213, 1171, 1134, 1113, 1088, 1052, 1017, 937, 900,
828, 757, 691, 653, 631, 606, 576, 547, 515. 1H- and 13C-NMR: Table 3. APCI-MS (pos.): 384 (100, [M þ
H ꢀ H2O]þ), 303 (23, [M þ H ꢀ C4H9NCO]þ). APCI-MS/MS (pos.) of 384: 328 (100, [M þ H ꢀ H2O ꢀ
C4H8]þ), 285 (19, [M þ H ꢀ H2O ꢀ C4H9NCO]þ), 272 (36, [M þ H ꢀ 2 C4H8]þ). APCI-MS (neg.): 400
(100, [M ꢀ H]ꢀ). APCI-MS/MS (neg.) of 400: 356 (94, [M ꢀ H ꢀ C3H7]ꢀ), 301 (43, [M ꢀ H ꢀ
C4H9NCO]ꢀ), 267 (41), 244 (100, [M ꢀ H ꢀ C4H9NCO ꢀ C4H9]ꢀ). Anal. calc. for C23H35N3O3 (401.54):
C 68.80, H 8.79, N 10.46; found: C 68.57, H 8.86, N 10.29.
3,3a-Dibutyl-3,3a,5,9b-tetrahydro-9b-hydroxy-5-methyl-1-phenyl-1H-imidazo[4,5-c]quinoline-2,4-
dione (3f). Prepared from 1f. Colorless crystals. M.p. 172 – 1808 (AcOEt). IR: 3316, 3063, 3037, 2959,
2934, 2870, 1692, 1664, 1602, 1500, 1470, 1417, 1371, 1356, 1300, 1264, 1206, 1173, 1137, 1114, 1094, 1054,
1
1019, 966, 913, 880, 855, 812, 760, 704, 691, 679, 664, 552, 604, 570, 557, 537, 503. H- and 13C-NMR:
Table 3. APCI-MS (pos.): 422 (4, [M þ H]þ), 404 (47, [M þ H ꢀ H2O]þ), 303 (100, [M þ H ꢀ
C6H5NCO]þ. APCI-MS/MS (pos.) of 422: 303 (100, [M þ H ꢀ C6H5NCO]þ). APCI-MS/MS (pos.) of
404: 348 (100, [M þ H ꢀ H2O ꢀ C4H8]þ), 305 (48, [M þ H ꢀ H2O ꢀ C4H9NCO]þ , 292 (29), 285 (19, [M þ
H ꢀ H2O ꢀ C6H5NCO]þ). APCI-MS (neg.): 420 (100, [M ꢀ H]ꢀ), 402 (24, [M ꢀ H ꢀ H2O]ꢀ). APCI-MS/
MS (neg.) of 420: 376 (8, [M ꢀ H ꢀ C3H8]ꢀ), 321 (14, [M ꢀ H ꢀ C4H9NCO]ꢀ), 301 (15, [M ꢀ H ꢀ
C6H5NCO]ꢀ), 244 (100, [M ꢀ H ꢀ C4H9NCO ꢀ C6H5]ꢀ). Anal. calc. for C25H31N3O3 (421.53): C 71.23,
H 7.41, N 9.97; found: C 71.40, H 7.53, N 9.72.
1,3-Dibutyl-3,3a,5,9b-tetrahydro-9b-hydroxy-5-methyl-3a-phenyl-1H-imidazo[4,5-c]quinoline-2,4-di-
one (3g). Prepared from 1g. Colorless crystals. M.p. 125 – 1288 (benzene/hexane). IR: 3417, 3284, 2958,
2931, 2871, 1686, 1604, 1501, 1471, 1406, 1368, 1312, 1268, 1210, 1142, 1109, 1052, 1020, 966, 934, 879, 837,
1
757, 708, 695, 631, 596, 548, 514. H- and 13C-NMR: Table 3. APCI-MS (pos.): 422 (6, [M þ H]þ), 404
(100, [M þ H ꢀ H2O]þ, 323 (30, [M þ H ꢀ C4H9NCO]þ). APCI-MS/MS (pos.) of 422: 323 (100, [M þ
H ꢀ C4H9NCO]þ). APCI-MS/MS of 404 (pos.): 348 (100, [M þ H ꢀ H2O ꢀ C4H8]þ), 292 (37, [M þ H ꢀ
H2O ꢀ 2 C4H8]þ). APCI-MS (neg.): 420 (100, [M ꢀ H]ꢀ). APCI-MS/MS (neg.) of 420: 376 (30,

704
Helvetica Chimica Acta – Vol. 92 (2009)
[M ꢀ H ꢀ C3H8]ꢀ), 363 (46, [M ꢀ H ꢀ C4H9]ꢀ), 346 (7, [M ꢀ H ꢀ H2O ꢀ C4H8]ꢀ), 321 (71, [M ꢀ H ꢀ
C4H9NCO]ꢀ), 288 (82), 264 (35, [M ꢀ H ꢀ C4H9NCO ꢀ C4H9]ꢀ), 244 (83, [M ꢀ H ꢀ C4H9NCO ꢀ
C6H5]ꢀ), 230 (100, [M ꢀ H ꢀ C4H9 ꢀ C4H8 ꢀ C6H5]ꢀ). Anal. calc. for C25H31N3O3 (421.53): C 71.23, H
7.41, N 9.97; found: C 71.35, H 7.46, N 9.59.
3-Butyl-3,3a,5,9b-tetrahydro-9b-hydroxy-5-methyl-1,3a-diphenyl-1H-imidazo[4,5-c]quinoline-2,4-di-
one (3h). Prepared from 1h. Colorless crystals. M.p. 214 – 2228 (benzene). IR: 3302, 3065, 2954, 2872,
1692, 1674, 1605, 1498, 1472, 1404, 1370, 1352, 1266, 1218, 1190, 1147, 1104, 1051, 1023, 965, 882, 825, 755,
1
726, 698, 679, 651, 633, 528. H- and 13C-NMR: Table 3. APCI-MS (pos.): 442 (5, [M þ H]þ), 424 (41,
[M þ H ꢀ H2O]þ), 323 (100, [M þ H ꢀ C6H5NCO]þ). APCI-MS/MS (pos.) of 442: 323 (100, [M þ H ꢀ
C6H5NCO]þ). APCI-MS/MS (pos.) of 424: 368 (100, [M þ H ꢀ H2O ꢀ C4H8]þ), 325 (19, [M þ H ꢀ
H2O ꢀ C4H9NCO]þ. APCI-MS (neg.): 440 (82, [M ꢀ H]ꢀ), 321 (69, [M ꢀ H ꢀ C6H5NCO]ꢀ), 250 (100).
APCI-MS/MS (neg.) of 440: 396 (4, [M ꢀ H ꢀ C3H8]ꢀ), 341 (47, [M ꢀ H ꢀ C4H9NCO]ꢀ), 321 (100, [M ꢀ
H ꢀ C6H5NCO]ꢀ), 264 (26, [M ꢀ H ꢀ C6H5NCO ꢀ C4H9]ꢀ). Anal. calc. for C27H27N3O3 (441.52): C 73.45,
H 6.16, N 9.52; found: C 73.52, H 6.29, N 9.38.
1,3,3a-Tributyl-3,3a,5,9b-tetrahydro-9b-hydroxy-5-phenyl-1H-imidazo[4,5-c]quinoline-2,4-dione
(3i). Prepared from 1i. Colorless crystals. M.p. 137 – 1428 (benzene/hexane). IR: 3284, 2958, 2931, 2871,
1678, 1603, 1592, 1497, 1465, 1422, 1370, 1335, 1304, 1271, 1211, 1167, 1129, 1071, 1059, 1021, 960, 936, 862,
828, 765, 756, 737, 700, 680, 627, 517. 1H- and 13C-NMR: Table 3. APCI-MS (pos.): 464 (10, [M þ H]þ), 446
(100, [M þ H ꢀ H2O]þ), 365 (13, [M þ H ꢀ C4H9NCO]þ). APCI-MS/MS (pos.) of 464: 365 (100, [M þ
H ꢀ C4H9NCO]þ). APCI-MS/MS (pos.) of 446: 390 (100, [M þ H ꢀ H2O ꢀ C4H8]þ), 347 (19, [M þ H ꢀ
C4H9NCO]þ), 334 (26, [M þ H ꢀ H2O ꢀ 2 C4H8]þ), 291 (10, [M þ H ꢀ 2 C4H8 ꢀ NHCO]þ). APCI-MS
(neg.): 462 (100, [M ꢀ H]ꢀ), 444 (15, [M ꢀ H ꢀ C6H5NCO]ꢀ). APCI-MS/MS (neg.) of 462: 363 (61,
[M ꢀ H ꢀ C4H9NCO]ꢀ), 267 (100, [M ꢀ H ꢀ C4H9NCO ꢀ C6H6 ꢀ H2O]ꢀ). Anal. calc. for C28H37N3O3
(463.61): C 72.54, H 8.04, N 9.06; found: C 72.68, H 8.22, N 8.91.
3,3a-Dibutyl-3,3a,5,9b-tetrahydro-9b-hydroxy-1,5-diphenyl-1H-imidazo[4,5-c]quinoline-2,4-dione
(3j). Prepared from 1j. Colorless crystals. M.p. 173 – 1768 (AcOEt/hexane). IR: 3343, 3061, 3039, 2956,
2931, 2871, 1692, 1681, 1603, 1495, 1461, 1412, 1362, 1334, 1605, 1273, 1254, 1182, 1130, 1091, 1077, 1023,
1
957, 919, 871, 857, 806, 770, 752, 735, 703, 654, 633, 598, 547, 517. H- and 13C-NMR: Table 3. APCI-MS
(pos.): 484 (7, [M þ H]þ), 466 (39, [M þ H ꢀ H2O]þ) , 365 (100), [M þ H ꢀ C6H5NCO]þ). APCI-MS/MS
(pos.) of 484: 365 (100, [M þ H ꢀ C6H5NCO]þ). APCI-MS/MS (pos.) of 466: 410 (100, [M þ H ꢀ H2O ꢀ
C4H8]þ), 367 (54, [M þ H ꢀ H2O ꢀ C4H9NCO]þ). APCI-MS (neg.): 482 (100, [M ꢀ H]ꢀ), 464 (17, [M ꢀ
H ꢀ H2O]ꢀ), 438 (26, [M ꢀ H ꢀ C3H8]ꢀ), 363 (6, [M þ H ꢀ C6H5NCO]þ). APCI-MS/MS (neg.) of 482:
438 (100, [M ꢀ H ꢀ C3H8]ꢀ). Anal. calc. for C30H33N3O3 (483.60): C 74.51, H 6.88, N 8.69;.found: C 74.58,
H 6.98, N 8.51.
1,3-Dibutyl-3,3a,5,9b-tetrahydro-9b-hydroxy-3a,5-diphenyl-1H-imidazo[4,5-c]quinoline-2,4-dione
(3k). Prepared from 1k. Colorless crystals. M.p. 108 – 1158 (benzene/hexane). IR: 3308, 3067, 3034, 2957,
2931, 2871, 1690, 1604, 1593, 1496, 1461, 1407, 1368, 1332, 1259, 1216, 1186, 1134, 1099, 1054, 1028, 1007,
941, 872, 832, 802, 759, 745, 700, 683, 658, 633, 615, 547, 522. 1H- and 13C-NMR: Table 3. APCI-MS (pos.):
466 (100, [M þ H ꢀ H2O]þ), 385 (53, [M þ H ꢀ C4H9NCO]þ). APCI-MS/MS (pos.) of 466: 410 (100,
[M þ H ꢀ H2O ꢀ C4H8]þ), 354 (30, [M þ H ꢀ H2O ꢀ 2 C4H8]þ). APCI-MS (neg.): 482 (100, [M ꢀ H]ꢀ),
312 (24). APCI-MS/MS (neg.) of 482: 438 (9, [M ꢀ H ꢀ C3H8]ꢀ), 287 (100, [M ꢀ H ꢀ C4H9NCO ꢀ
C6H6 ꢀ H2O]ꢀ), 230 (34). Anal. calc. for C30H33N3O3 (483.60): C 74.51, H 6.88, N 8.69; found: C 74.65, H
6.93, N 8.59.
3-Butyl-3,3a,5,9b-tetrahydro-9b-hydroxy-1,3a,5-triphenyl-1H-imidazo[4,5-c]quinoline-2,4-dione
(3l). Prepared from 1l. Colorless crystals. M.p. 207 – 2128 (benzene/cyclohexane). IR: 3424, 3064, 3037,
2959, 2931, 2872, 1709, 1682, 1603, 1495, 1460, 1396, 1366, 1329, 1261, 1157, 1135, 1107, 1084, 1054, 1025,
1
1008, 942, 913, 875, 827, 755, 699, 653, 636, 615, 585, 535, 500. H- and 13C-NMR: Table 3. APCI-MS
(pos.): 504 (3, [M þ H]þ), 486 (25, [M þ H ꢀ H2O]þ), 466 (10), 385 (100, [M þ H ꢀ C6H5NCO]þ). APCI-
MS/MS (pos.) of 504: 385 (81, [M þ H ꢀ C6H5NCO]þ), 309 (100, [M þ H ꢀ C4H9NCO ꢀ C6H6 ꢀ H2O]þ),
196 (21). APCI-MS/MS (pos.) of 486: 430 (100, [M þ H ꢀ H2O ꢀ C4H8]þ). APCI-MS (neg.): 502 (52,
[M ꢀ H]ꢀ), 482 (7), 458 (6, [M ꢀ H ꢀ C3H8]ꢀ), 383 (26, [M ꢀ H ꢀ C6H5NCO]ꢀ), 312 (100, [M ꢀ H ꢀ
C6H5NCONC4H9]ꢀ). APCI-MS/MS (neg.) of 502: 458 (43, [M ꢀ H ꢀ C3H8]ꢀ), 383 (100, [M ꢀ H ꢀ

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C6H5NCO]ꢀ), 307 (23, [M ꢀ H ꢀ C4H9NCO ꢀ C6H6 ꢀ H2O]ꢀ). Anal. calc. for C32H29N3O3 (503.59): C
76.32, H 5.80, N 8.34; found: C 76.47, H 6.03, N 8.14.
5. Molecular Rearrangement of Compounds 2 and 3: General Procedures. Method A: A soln. of 2 or 3
(1 mmol) in AcOH (8 ml) was heated to reflux for the time given in Table 4. After cooling, the mixture
was concentrated, and the residue was crystallized from an appropriate solvent or separated by CC
(SiO2).
Method B: A soln. of 2 or 3 (1 mmol) in conc. HCl soln. (5 ml) was heated to reflux for the time
given in Table 4. A small quantity of AcOH was added to dissolve the starting compound. After cooling,
the precipitated product was filtrated off with suction and recrystallized from an appropriate solvent.
When the mixture was homogeneous, it was concentrated, and the residue was crystallized from an
appropriate solvent or separated by CC (SiO2).
(5E)-3-Butyl-5-butylidene-1’-methylspiro[imidazolidine-4,3’-[3H]indole]-2,2’(1’H)-dione (10a).
Prepared from 3a (besides N-methylisatin). Colorless crystals. M.p. 117 – 1218 (cyclohexane). IR:
3177, 3050, 2957, 2930, 2872, 1722, 1688, 1613, 1493, 1474, 1449, 1416, 1364, 1350, 1317, 1277, 1242, 1169,
1128, 1098, 1045, 958, 877, 763, 685, 643, 537, 487. 1H- and 13C-NMR: Table 5. APCI-MS (pos.): 328 (100,
[M þ H]þ). APCI-MS/MS (pos.) of 328: 311 (5, [M þ H ꢀ NH3]þ), 285 (19, [M þ H ꢀ NHCO]þ), 272
(100, [M þ H ꢀ C4H8]þ), 255 (90), 229 (98, [M þ H ꢀ C4H9NCO]þ). APCI-MS (neg.): 326 (100, [M ꢀ
H]ꢀ). APCI-MS/MS (neg.) of 326: 283 (4, [M ꢀ H ꢀ NHCO]ꢀ), 269 (26, [M ꢀ H ꢀ C4H9]ꢀ), 240 (5,
[M ꢀ H ꢀ C5H8 ꢀ CO]ꢀ), 227 (100, [M ꢀ H ꢀ C4H9NCO]ꢀ). Anal. calc. for C19H25N3O2 (327.42): C 69.70,
H 7.70, N 12.83; found: C 69.85, H 7.85, N 12.71.
(5E)-5-Butylidene-1’-methyl-3-phenyl-1’H-spiro[imidazolidine-4,3’-[3H]indole]-2,2’(1’H)-dione
(10b). Prepared from 2b. Colorless crystals. M.p. 186 – 1918 (benzene/hexane). IR: 3447, 3193, 3071, 2951,
2928, 2867, 1733, 1697, 1613, 1494, 1469, 1391, 1367, 1304, 1250, 1190, 1156, 1127, 1088, 1020, 969, 902, 876,
826, 779, 746, 702, 678, 553, 539, 504. 1H- and 13C-NMR: Table 5. APCI-MS (pos.): 348 (100, [M þ H]þ).
APCI-MS/MS (pos.) of 348: 305 (11, [M þ H ꢀ NHCO]þ), 292 (17, [M þ H ꢀ C4H8]þ), 255 (100, [M þ
H ꢀ C6H5NH2]þ), 229 (79, [M þ H ꢀ C6H5NCO]þ). APCI-MS (neg.): 346 (100, [M ꢀ H]ꢀ). APCI-MS/
MS (neg.) of 346: 318 (32, [M ꢀ H ꢀ CO]ꢀ), 303 (100, [M ꢀ H ꢀ NHCO]ꢀ), 287 (10), 260 (19, [M ꢀ H ꢀ
C5H8 ꢀ CO]ꢀ), 254 (56), 227 (57, [M ꢀ H ꢀ C6H5NCO]ꢀ). Anal. calc. for C21H21N3O2 (347.16): C 72.60, H
6.09, N 12.10; found: C 72.31, H 6.13, N 11.84.
(5E)-1,3-Dibutyl-5-butylidene-1’-methylspiro[imidazolidine-4,3’-[3H]indole]-2,2’(1’H)-dione (10e).
Prepared from 3e. Yellowish oil. IR: 3056, 2957, 2931, 2871, 1728, 1674, 1611, 1491, 1468, 1418, 1366, 1342,
1
1311, 1255, 1191, 1128, 1096, 1021, 938, 814, 753, 695, 676, 538. H- and 13C-NMR: Table 5. APCI-MS
(pos.): 384 (100, [M þ H]þ). APCI-MS/MS (pos.) of 384: 328 (100, [M þ H ꢀ C4H8]þ), 285 (17, [M þ
H ꢀ C4H9NCO]þ), 272 (30, [M þ H ꢀ 2 C4H8]þ). APCI-MS (neg.): 382 (21, [M ꢀ H]ꢀ), 414 (100). APCI-
MS/MS (neg.) of 382: 325 (100, [M ꢀ H ꢀ C4H9]ꢀ), 308 (22, [M ꢀ H ꢀ C4H8 ꢀ H2O]ꢀ), 268 (47, [M ꢀ
H ꢀ 2 C4H9]ꢀ). Anal. calc. for C23H33N3O2 (383.53): C 72.03, H 8.67, N 10.96; found: C 72.11, H 8.52, N
10.89.
(5E)-1-Butyl-5-butylidene-1’-methyl-3-phenylspiro[imidazolidine-4,3’-[3H]indole]-2,2’(1’H)-dione
(10f). Prepared from 3f. Colorless crystals. M.p. 118 – 1228 (benzene/hexane). IR: 3053, 2959, 2933, 2871,
2833, 1728, 1711, 1671, 1611, 1492, 1469, 1419, 1358, 1341, 1259, 1241, 1202, 1123, 1085, 1032, 982, 944, 920,
892, 812, 771, 760, 743, 692, 674, 654, 621, 538, 511. 1H- and 13C-NMR: Table 5. APCI-MS (pos.): 404 (100,
[M þ H]þ). APCI-MS/MS (pos.) of 404: 348 (100, [M þ H ꢀ C4H8]þ), 305 (47, [M þ H ꢀ C4H9NCO]þ),
292 (35, [M þ H ꢀ 2 C4H8]þ). APCI-MS (neg.): 402 (100, [M ꢀ H]ꢀ). APCI-MS/MS (neg.) of 402: 316
(100, [M ꢀ H ꢀ C5H8 ꢀ CO]ꢀ), 303 (29, [M ꢀ H ꢀ C4H9NCO]ꢀ), 260 (86, [M ꢀ H ꢀ C5H8 ꢀ CO ꢀ
C4H8]ꢀ). Anal. calc. for C25H29N3O2 (403.52): C 74.41, H 7.24, N 10.41; found: C 74.57, H 7.32, N 10.29.
(5E)-1,3-Dibutyl-5-butylidene-1’-phenylspiro[imidazolidine-4,3’-[3H]indole]-2,2’(1’H)-dione (10i).
Prepared from 3i. Colorless crystals. M.p. 52 – 558 (hexane). IR: 3066, 2953, 2927, 2867, 1742, 1722,
1674, 1611, 1594, 1529, 1500, 1465, 1454, 1420, 1371, 1312, 1296, 1263, 1226, 1194, 1179, 1158, 1104, 1088,
954, 937, 869, 819, 809, 766, 757, 702, 678, 661, 626, 522. 1H- and 13C-NMR: Table 5. APCI-MS (pos.): 446
(100, [M þ H]þ). APCI-MS/MS (pos.) of 446: 390 (100, [M þ H ꢀ C4H8]þ), 372 (7, [M þ H ꢀ H2O ꢀ
C4H8]þ), 347 (21, [M þ H ꢀ C4H9NCO]þ), 334 (23, [M þ H ꢀ 2 C4H8]þ). APCI-MS (neg.): 444 (100,
[M ꢀ H]ꢀ). APCI-MS/MS (neg.) of 444: 387 (100, [M ꢀ H ꢀ C4H9]ꢀ), 358 (9, [M ꢀ H ꢀ C5H8 ꢀ CO]ꢀ),

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Helvetica Chimica Acta – Vol. 92 (2009)
330 (23, [M ꢀ H ꢀ 2 C4H9]ꢀ). Anal. calc. for C28H35N3O2 (445.60): C 75.47, H 7.92, N 9.43; found: C 75.61,
H 7.83, N 9.13.
(5E)-1-Butyl-5-butylidene-1’,3-diphenylspiro[imidazolidine-4,3’-[3H]indole]-2,2’(1’H)-dione (10j).
Prepared from 3j. Colorless crystals. M.p. 86 – 888 (hexane). IR: 3060, 3032, 2959, 2931, 2904, 2867,
1722, 1680, 1612, 1592, 1495, 1465, 1453, 1417, 1361, 1324, 1294, 1252, 1222, 1204, 1187, 1175, 1125, 1072,
1043, 1025, 1002, 972, 947, 896, 858, 809, 759, 745, 698, 678, 666, 644, 622, 537. 1H- and 13C-NMR: Table 5.
APCI-MS (pos.): 466 (100, [M þ H]þ). APCI-MS/MS (pos.) of 466: 410 (100, [M þ H ꢀ C4H8]þ), 367
(55, [M þ H ꢀ C4H9NCO]þ), 354 (27, [M þ H ꢀ 2 C4H8]þ), 347 (20, [M þ H ꢀ C6H5NCO]þ). APCI-MS
(neg.): 464 (100, [M ꢀ H]ꢀ). APCI-MS/MS (neg.) of 464: 378 (100, [M ꢀ H ꢀ C5H8 ꢀ CO]ꢀ), 365 (16,
[M ꢀ H ꢀ C4H9NCO]ꢀ), 322 (32, [M ꢀ H ꢀ C5H8 ꢀ CO ꢀ C4H8]ꢀ). Anal. calc. for C30H31N3O2 (465.59): C
77.39, H 6.71, N 9.03; found: C 77.23, H 6.97, N 9.00.
3-Butyl-1’-methyl-5-phenylspiro[4H-imidazol-4,3’-[3H]indole]-2,2’(1’H,3H)-dione (11c). Prepared
from 2c and from 3c. Colorless crystals. M.p. 163 – 1658 (benzene/hexane). IR: 2959, 2931, 2872, 1737,
1724, 1714, 1611, 1591, 1563, 1492, 1473, 1446, 1365, 1348, 1326, 1263, 1181, 1132, 1103, 1083, 1043, 1022,
964, 930, 840, 772, 699, 685, 589, 539. 1H- and 13C-NMR: Table 5. APCI-MS (pos.): 348 (100, [M þ H]þ).
APCI-MS/MS (pos.) of 348: 292 (100, [M þ H ꢀ C4H8]þ), 306 (3, [M þ H ꢀ NCO]þ), 249 (8, [M þ H ꢀ
C4H9NCO]þ), 217 (14, [M þ H ꢀ C6H5 ꢀ CNCO]þ), 160 (19, [M þ H ꢀ C6H5 ꢀ CNCO ꢀ C4H9]þ). Anal.
calc. for C21H21N3O2 (347.41): C 72.60, H 6.09, N 12.10; found: C 72.55, H 6.17, N 11.87.
1’-Methyl-1,5-diphenylspiro[4H-imidazol-4,3’-[3H]indole]-2,2’(1’H,3H)-dione (11d). Prepared from
2d and from 3d. Colorless crystals. M.p. 290 – 2918 (benzene). IR: 1738, 1721, 1611, 1589, 1555, 1492, 1471,
1447, 1416, 1359, 1295, 1254, 1206, 1127, 1066, 1024, 974, 949, 835, 771, 702, 682, 589, 538. 1H- and
13C-NMR: Table 5. APCI-MS (pos.): 368 (100, [M þ H]þ). APCI-MS/MS (pos.) of 368: 325 (16, [M þ
H ꢀ NHCO]þ), 237 (19, [M þ H ꢀ C6H5 ꢀ CNCO]þ), 180 (100, [M þ H ꢀ C6H5 ꢀ CNCO ꢀ C4H9]þ).
Anal. calc. for C23H17N3O2 (367.40): C 75.19, H 4.66, N 11.44; found: C 75.31, H 4.47, N 11.17.
(4R*,5S*)-1,3-Dibutyl-5-hydroxy-1’-methyl-5-phenylspiro[imidazolidine-4,3’-[3H]indole]-2,2’(1’H)-
dione (12Ag). Prepared from 3g and 12Bg. Colorless crystals. M.p. 165 – 1718 (benzene). IR: 3383, 3056,
2959, 2934, 2872, 1721, 1704, 1613, 1493, 1469, 1451, 1403, 1370, 1310, 1263, 1200, 1177, 1134, 1108, 1094,
1
1063, 1050, 1024, 930, 885, 830, 755, 704, 672, 655, 640, 539, 516. H- and 13C-NMR: Table 6. APCI-MS
(pos.): 422 (2, [M þ H]þ), 404 (100, [M þ H ꢀ H20]þ), 378 (10, [M þ H ꢀ C3H8]þ). APCI-MS/MS (pos.)
of 422: 404 (5, [M þ H ꢀ H2O]þ), 323 (100, [M þ H ꢀ C4H9NCO]þ), 300 (26). APCI-MS/MS (pos.) of
404: 348 (100, [M þ H ꢀ H2O ꢀ C4H8]þ), 292 (44, [M þ H ꢀ H2O ꢀ 2 C4H8]þ). APCI-MS (neg.): 420 (100,
[M ꢀ H]ꢀ). APCI-MS/MS (neg.) of 420: 363 (75, [M ꢀ H ꢀ C4H9]ꢀ), 321 (100, [M ꢀ C4H9NCO]ꢀ), 264
(80, [M ꢀ H ꢀ C4H9NCO ꢀ C4H9]ꢀ), 176 (14), 121 (68). Anal. calc. for C25H31N3O3 (421.53): C 71.23, H
7.41, N 9.97; found: C 71.45, H 7.30, N 9.83.
(4R*,5R*)-1,3-Dibutyl-5-hydroxy-1’-methyl-5-phenylspiro[imidazolidine-4,3’-[3H]indole]-2,2’(1’H)-
dione (12Bg). Prepared from 3g. Yellowish oil. IR: 3386, 3059, 2957, 2931, 2870, 1710, 1612, 1492, 1468,
1414, 1370, 1348, 1258, 1176, 1133, 1108, 1094, 1073, 1023, 880, 831, 751, 698, 667, 579, 539. 1H- and
13C-NMR: Table 6. APCI-MS (pos.): 404 (100, [M þ H ꢀ H20]þ), 378 (4, [M þ H ꢀ C3H8]þ), 348 (4, [M þ
H ꢀ H2O ꢀ C4H8]þ). APCI-MS/MS (pos.) of 404: 348 (100, [M þ H ꢀ H2O ꢀ C4H8]þ), 292 (39, [M þ
H ꢀ H2O ꢀ 2 C4H8]þ). APCI-MS (neg.): 420 (100, [M ꢀ H]ꢀ). APCI-MS/MS (neg.) of 420: 363 (66,
[M ꢀ H ꢀ C4H9]ꢀ), 321 (100, [M ꢀ C4H9NCO]ꢀ), 287 (26, [M ꢀ H ꢀ C6H5 ꢀ C4H8]ꢀ), 264 (65, [M ꢀ H ꢀ
C4H9NCO ꢀ C4H9]ꢀ), 230 (34), 176 (15), 121 (56). Anal. calc. for C25H31N3O3 (421.53): C 71.23, H 7.41, N
9.97; found: C 71.54, H 7.57, N 10.03.
(4R*,5S*)-1-Butyl-5-hydroxy-1’-methyl-3,5-diphenylspiro[imidazolidine-4,3’-[3H]indole]-2,2’(1’H)-
dione (12Ah). Prepared from 3h and 12Bh. Colorless crystals. M.p. 234 – 2388 (benzene). IR: 3315, 3065,
3031, 2957, 2934, 2869, 1728, 1698, 1616, 1555, 1499, 1473, 1453, 1394, 1360, 1323, 1267, 1251, 1206, 1179,
1123, 1094, 1051, 1028, 935, 895, 843, 820, 752, 699, 661, 645, 542, 515. 1H- and 13C-NMR: Table 6. APCI-
MS (pos.): 442 (6, [M þ H]þ), 424 (100, [M þ H ꢀ H2O]þ). APCI-MS/MS (pos.) of 442: 424 (7, [M þ
H ꢀ H2O]þ), 343 (100, [M þ H ꢀ C4H9NCO]þ), 325 (83, [M þ H ꢀ H2O ꢀ C4H9NCO]þ). APCI-MS/MS
(pos.) of 424: 368 (100, [M þ H ꢀ H2O ꢀ C4H8]þ), 325 (19, [M þ H ꢀ H2O ꢀ C4H9NCO]þ). APCI-MS
(neg.): 440 (100, [M ꢀ H]ꢀ), 502 (15). APCI-MS/MS (neg.) of 440: 396 (3, [M ꢀ H ꢀ C3H8]ꢀ), 341 (100,
[M ꢀ H ꢀ C4H9NCO]ꢀ). Anal. calc. for C27H27N3O3 (441.52): C 73.45, H 6.16, N 9.52; found: C 73.26, H
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(4R*,5R*)-1-Butyl-5-hydroxy-1’-methyl-3,5-diphenylspiro[imidazolidine-4,3’-[3H]indole]-2,2’(1’H)-
dione (12Bh). Prepared from 3h. Colorless crystals. M.p. 171 – 1758 and then 231 – 2348 (benzene/
hexane). IR: 3356, 3057, 2974, 2948, 2868, 1713, 1702, 1613, 1600, 1500, 1470, 1445, 1412, 1368, 1341, 1315,
1204, 1264, 1221, 1176, 1123, 1088, 1058, 1042, 1026, 1002, 957, 936, 916, 844, 822, 786, 764, 752, 695, 657,
639, 542, 517. 1H- and 13C-NMR: Table 6. APCI-MS (pos.): 442 (1, [M þ H]þ), 424 (100, [M þ H ꢀ
H2O]þ), 320 (7). APCI-MS/MS (pos.) of 442: 424 (33, [M þ H ꢀ H2O]þ), 398 (38, [M þ H ꢀ C3H8]þ),
343 (100, [M þ H ꢀ C4H9NCO]þ), 325 (90, [M þ H ꢀ H2O ꢀ C4H9NCO]þ). APCI-MS/MS (pos.) of 424:
368 (100, [M þ H ꢀ H2O ꢀ C4H8]þ), 325 (16, [M þ H ꢀ H2O ꢀ C4H9NCO]þ), 237 (30). APCI-MS (neg.):
440 (100, [M ꢀ H]ꢀ), 250 (16). APCI-MS/MS (neg.) of 440: 396 (3, [M ꢀ H ꢀ C3H8]ꢀ), 341 (100, [M ꢀ
H ꢀ C4H9NCO]ꢀ). Anal. calc. for C27H27N3O3 (441.52): C 73.45, H 6.16, N 9.52; found: C 73.31, H 6.34, N
9.40.
(4R*,5S*)-1,3-Dibutyl-5-hydroxy-1’,5-diphenylspiro[imidazolidine-4,3’-[3H]indole]-2,2’(1’H)-dione
(12Ak). Prepared from 3k and 12Bk. Colorless crystals. M.p. 142 – 1468 (benzene/cyclohexane). IR: 3447,
3305, 3057, 2957, 2925, 2872, 1736, 1682, 1611, 1595, 1500, 1468, 1419, 1374, 1333, 1248, 1209, 1176, 1111,
1058, 1029, 992, 938, 892, 851, 831, 817, 771, 754, 736, 699, 670, 610, 527, 512. 1H- and 13C-NMR: Table 6.
APCI-MS (pos.): 466 (100, [M þ H ꢀ H2O]þ). APCI-MS/MS (pos.) of 466: 410 (100, [M þ H ꢀ H2O ꢀ
C4H8]þ), 354 (32, [M þ H ꢀ H2O ꢀ 2 C4H8]þ). APCI-MS (neg.): 482 (100, [M ꢀ H]ꢀ). APCI-MS/MS
(neg.) of 482: 438 (100, [M ꢀ H ꢀ C3H8]ꢀ), 383 (47, [M ꢀ C4H9NCO]ꢀ), 339 (29, [M ꢀ H ꢀ C4H9NCO ꢀ
C3H8]ꢀ), 176 (18). Anal. calc. for C30H33N3O3 (483.60): C 74.51, H 6.88, N 8.69; found: C 74.57, H 6.93, N
8.48.
(4R*,5R*)-1,3-Dibutyl-5-hydroxy-1’,5-diphenylspiro[imidazolidine-4,3’-[3H]indole]-2,2’(1’H)-dione
(12Bk). Prepared from 3k. Colorless crystals. M.p. 111 – 1148 (hexane). IR: 3440, 3059, 2957, 2930, 2870,
1725, 1705, 1611, 1594, 1501, 1466, 1413, 1371, 1330, 1306, 1237, 1207, 1183, 1161, 1135, 1115, 1074, 1027,
1001, 926, 880, 752, 701, 670, 619, 578, 530, 511. APCI-MS (pos.): 484 (2, [M þ H]þ), 466 (100, [M þ H ꢀ
H2O]þ). APCI-MS/MS (pos.) of 484: 466 (16, [M þ H ꢀ H2O]þ), 385 (100, [M þ H ꢀ C4H9NCO]þ), 362
(65). APCI-MS (neg.): 482 (100, [M ꢀ H]ꢀ), 312 (38). APCI-MS/MS (neg.) of 482: 438 (100, [M ꢀ H ꢀ
C3H8]ꢀ), 383 (45, [M ꢀ H ꢀ C4H9NCO]ꢀ), 339 (26, [M ꢀ H ꢀ C4H9NCO ꢀ C3H8]ꢀ), 326 (16, [M ꢀ H ꢀ
C4H9NCO ꢀ C4H9]ꢀ). Anal. calc. for C30H33N3O3 (483.60): C 74.51, H 6.88, N 8.69; found: C 74.27, H 7.01,
N 8.53.
(4R*,5S*)-1-Butyl-5-hydroxy-1’,3,5-triphenylspiro[imidazolidine-4,3’-[3H]indole]-2,2’(1’H)-dione
(12Al). Prepared from 3l and 12Bl. Colorless crystals. M.p. 194 – 1968 (benzene/hexane). IR: 3419, 3287,
3064, 2959, 2932, 2870, 1735, 1690, 1672, 1610, 1500, 1466, 1452, 1408, 1368, 1306, 1246, 1210, 1177, 1125,
1093, 1061, 1028, 993, 941, 896, 843, 803, 753, 699, 665, 620, 581, 522. 1H- and 13C-NMR: Table 6. APCI-MS
(pos.): 486 (100, [M þ H ꢀ H2O]þ, 382 (3). APCI-MS/MS (pos.) of 486: 430 (100, [M þ H ꢀ H2O ꢀ
C4H8]þ), 387 (21, [M þ H ꢀ H2O ꢀ C4H9NCO]þ), 299 (58). APCI-MS (neg.): 502 (95, [M ꢀ H]ꢀ), 312
(100). APCI-MS/MS (neg.) of 502: 458 (13, [M ꢀ H ꢀ C3H8]ꢀ), 403 (100, [M ꢀ H ꢀ C4H9NCO]ꢀ), 359
(4, [M ꢀ H ꢀ C4H9NCO ꢀ C3H8]ꢀ). Anal. calc. for C32H29N3O3 (503.59): C 76.32, H 5.80, N 8.34; found: C
76.16, H 6.01, N 8.55.
(4R*,5R*)-1-Butyl-5-hydroxy-1’,3,5-triphenylspiro[imidazolidine-4,3’-[3H]indole]-2,2’(1’H)-dione
(12Bl). Prepared from 3l. Colorless crystals. M.p. 139 – 1468 (cyclohexane). IR: 3433, 3061, 3034, 2959,
2929, 2870, 1732, 1707, 1611, 1595, 1497, 1467, 1451, 1401, 1356, 1326, 1299, 1253, 1206, 1177, 1125, 1099,
1067, 1026, 939, 874, 843, 812, 796, 751, 701, 622, 583. APCI-MS (pos.): 504 (10, [M þ H]þ), 486 (100,
[M þ H ꢀ H2O]þ). APCI-MS/MS (pos.) of 504: 486 (6, [M þ H ꢀ H2O]þ), 460 (5, [M þ H ꢀ C3H8]þ),
405 (100, [M þ H ꢀ C4H9NCO]þ), 387 (23, [M þ H ꢀ C4H9NCO ꢀ H2O]þ). APCI-MS (neg.): 502 (100,
[M ꢀ H]ꢀ). APCI-MS/MS (neg.) of 502: 458 (14, [M ꢀ H ꢀ C3H8]ꢀ), 403 (100, [M ꢀ H ꢀ C4H9NCO]ꢀ).
Anal. calc. for C32H29N3O3: C 76.32, H 5.80, N 8.34; found: C 76.12, H 5.97, N 8.41.
6. Interconversion of Compounds 12B and 12A: General Procedure. A soln. of pure 12B (0.1 mmol)
in a mixture of conc. HCl soln. (1.5 ml) and AcOH (1 ml) was heated to reflux for 4 h. After cooling, the
mixture was concentrated, and the residue was crystallized from an appropriate solvent. The following
compounds 12A, identical in all respects to those prepared from 3 (see Sect. 5) were prepared (yields in
[%]): 12Ag (48), 12Ah (64), 12Ak (37), and 12Al (63). In the mother liquors, the presence of both
compounds 12A and 12B was evidenced by TLC. Under the same conditions, but starting from 12A,

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Helvetica Chimica Acta – Vol. 92 (2009)
mixtures 12A/12B were obtained (verified by TLC). Due to a small content of 12B in these mixtures,
their isolation failed.
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Received August 29, 2008