Recyclization in the series of spiro[indole-3,5′-pyrimido[4,5-b] quinoline]-2,2′,4′-triones prepared by a three-component reaction of isatins with (thio)barbituric acids and electron-rich anilines

Article abstract of DOI:10.1055/s-0032-1318273

A ring-ring transformation in the series of spiro[indole-3,5′- pyrimido[4,5-b]quinoline]-2,2′,4′-trione derivatives prepared by a three-component reaction of (thio)barbituric acids, electron-rich aromatic amines, and isatins was observed. Georg Thieme Verlag Stuttgart - New York.

Full text of DOI:10.1055/s-0032-1318273

PAPER
▌971
pRapeercyclization in the Series of Spiro[indole-3,5′-pyrimido[4,5-b]quinoline]-
2,2′,4′-triones Prepared by a Three-Component Reaction of Isatins with
(
Thio)barbituric Acids and Electron-Rich Anilines
Ring–Ring Transformation in Spirotriones
a,b
a
c
a
a,d
Viktor O. Iaroshenko,* Sergii Dudkin, Vyacheslav Ya. Sosnovskikh, Alexander Villinger, Peter Langer
a
Institut für Chemie, Universität Rostock, Albert Einstein Str. 3a, 18059 Rostock, Germany
E-mail: viktor.iaroshenko@uni-rostock.de; E-mail: iva108@googlemail.com
b
National Taras Shevchenko University, 62 Volodymyrska Str., 01033 Kyiv, Ukraine
c
Department of Chemistry, Ural Federal University, 51 Lenina Ave., 620000 Ekaterinburg, Russian Federation
d
Leibniz-Institut für Katalyse an der Universität Rostock e.V., Albert Einstein Str. 29a, 18059 Rostock, Germany
Received: 10.12.2012; Accepted after revision: 30.01.2013
Abstract: A ring–ring transformation in the series of spiro[indole-
N
3,5′-pyrimido[4,5-b]quinoline]-2,2′,4′-trione derivatives prepared
O
Me
H
by a three-component reaction of (thio)barbituric acids, electron-
rich aromatic amines, and isatins was observed.
N
H
O
N
MeO
Key words: multicomponent reaction, barbituric acids, aromatic
O
N
O
amines,
isatins,
spiro[indole-3,5′-pyrimido[4,5-b]quinoline]-
H
2,2′,4′-triones, recyclization
MeO
N
horsfiline
H
spirotryprostatin A
O
N
OBn
O
The heterocyclic oxindole system containing one carbon
atom common to two rings is a widely distributed struc-
tural framework present in a number of pharmaceuticals
N
O
HN
H
N
NH3
O
N
1
and natural products. The presence of the chiral spiro car-
MeSO3
bon leads to the sterically constrained spiro structure and
is one of the important factors of the biological activities.
Thus, the spirooxindole and spiroindoline ring systems
are present in a number of natural alkaloids, including an-
esthetics (horsfiline),2 mammalian cell cycle inhibitors
O
N
H
SO2Me
ibutamoren mesylate
spirotryprostatin B
a
2
b
(
spirotryprostatins A and B), and in synthetic drugs (for
NH2
instance, ibutamoren mesylate, an orally active nonpep-
NO2
CO Me
HN
3
tide growth hormone secretagogue ) (Figure 1).
MeO C
Cl
O
2
2
HN
On the other hand, the target scaffold includes so impor-
tant motifs such as 6-aminouracil and 1,4-dihydropyri-
dine. The latter are known to be calcium agonists and
N
H
O
N
H
nifedipine
AEAC
4
calcium channel blockers (for example, nifedipine). 6-(2-
Figure 1 Representatives of important spiroindoles, 1,4-dihydropyri-
dines, and 6-aminouracils
Aminoethyl)amino-5-chlorouracil (AEAC), which be-
longs to a class of 6-aminouracils, is a thymidine phos-
5
phorylase inhibitor and exhibits antitumor activity
(
Figure 1). The combination of these moieties presents in-
torial and medicinal chemistry and are particularly useful
triguing possibilities for pharmacological studies and
drug design.
6
for the preparation of spiro heterocyclic systems.
6h
Iaroshenko and co-workers have recently communicat-
Multicomponent reactions (MCRs) as the synthetic ap- ed a practical route to 7-azaindole framework by a one-
proach to such scaffolds are very advantageous in many pot, three-component cyclocondensation of N-substituted
aspects. Such reactions offer a wide range of possibilities 2-amino-4-cyanopyrroles, various aldehydes, and active
for the efficient construction of complex molecules in a methylene compounds.
single procedural step and are perfectly amenable to auto-
mation for combinatorial synthesis. Because of their con-
vergence and productivity, the MCRs have attracted
considerable attention from the point of view of combina-
7
Continuing our research program on the efficient synthe-
sis of drug-like fused pyridines, we have undertaken at-
tempts in the context of special interest in the synthesis of
spiro heterocycles containing uracil, 1,4-dihydropyridine,
and indole ring fragments by a three-component reaction
of (thio)barbituric acids, aromatic amines, and isatins. We
now report that such compounds can be obtained under
mild reaction conditions in the presence of iodine. More-
SYNTHESIS 2013, 45, 0971–0977
Advanced online publication: 14.02.2013
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0032-1318273; Art ID: SS-2012-Z0951-OP
Georg Thieme Verlag Stuttgart · New York
©

972
V. O. Iaroshenko et al.
PAPER
over, in the case of N-unsubstituted isatins, unexpected
recyclization of spiro[indole-3,5′-pyrimido[4,5-b]quino-
line]-2,2′,4′-trione derivatives was observed.
O
N
R1
1
O
R1
X
R3
N
+
O
O
N
R4
Recently, there have been many reports on the synthesis
of spiro[dihydropyridine-oxindole] compounds from isat-
3
8
ins, 2-naphthylamine, and 1,3-dicarbonyls as well as
R4
+
9
from isatins, heterocyclic amines, and barbituric acids
O
N
O
via the Hantzsch-like reaction in the presence of various
catalysts and under various conditions. However, to the
best of our knowledge, there are no literature data for the
preparation of spiroindolinone derivatives from isatins,
aromatic amines, and barbituric acids.10
R2
R1
X
NH2
N
2
R3
O
N
R1
A
–
H2O
EtOH, I2
r.t., 24 h
We report now on the formation of spiro[indole-3,5′-py-
rimido[4,5-b]quinoline]-2,2′,4′-triones from barbituric
and thiobarbituric acids, electron-rich anilines, and N-
substituted and N-unsubstituted isatins. Thus, four com-
mercially available barbituric acid derivatives 1, three
electron-rich anilines 2, and six isatins 3 were chosen for
the library validation.
R4
N
NH
R2
O
O
R3
O
O
R1
R3
R1
N
N
R2
R4 = H
N
R1
X
N
R1
X
NH2
O
NH2
O
B
C
In the initial study, we have developed the synthesis of the
hitherto unknown spiro heterocycles 4 starting from N-
methyl- and N-ethylisatins by a one-pot, three-component
reaction depicted in Scheme 1. Different catalysts and sol-
vents were first briefly examined and the best result was
obtained by using iodine as catalyst and EtOH as the sol-
R4 = Me, Et
R4
–
H2O
– H2O
N
NH
R2
O
O
R3
O
O
R1
X
R3
R1
X
11
N
N
vent. It was found that treatment of N-substituted isatins
with dimethylbarbituric or diethylthiobarbituric acids and
anilines (3,5-dimethoxy-, 3,4,5-trimethoxyanilines, 2-an-
thracenamine) in ethanol in the presence of a catalytic
R2
N
H
N
R1
N
N
R1
H
4
a–k
5a–n
amount of iodine (0.05 equiv) at room temperature result- Scheme 1 Synthesis of isomeric spiro[indole-3,5′-pyrimido[4,5-
b]quinoline]-2,2′,4′-triones 4 and 5 by a three-component reaction
ed in the formation of expected spiroindolinones 4a–i in
moderate to high yields (47–86%). In most cases, the re-
action was complete after 24 hours and the products could
derivatives 5a–l were obtained in variable 26–91% yields
Table 1). Their spectral data were similar but inconsistent
be isolated by simple filtration of the precipitate formed.
The progress of the reaction was monitored by TLC, and
the results are summarized in Table 1. It is important that
only electron-rich anilines 2 can effectively participate in
the reaction with 1 and 3, providing a variety of com-
pounds 4 with high purity. The regiochemistry of 4c and
(
with the expected structure 4. Indeed, the data were in
good agreement with the structure of an unexpected prod-
uct 5, being constructed via ring-opening of N-unsubsti-
tuted spiroindolinone fragment followed by formation of
a dihydropyridine ring from intermediate C. Selected
NMR spectral data of isomers 4 and 5 (Figure 2) are sum-
marized in Tables 2–5. It should be also noted that singlets
for the dihydropyridine proton H-10′ in 4 and 5 appeared
at δ = 9.16–9.22 and 9.14–9.59, respectively. To confirm
the conclusion about the regiochemistry of 5, additional
4f was confirmed by 2D NOESY experiments. Spiroindo-
linones 4 are likely formed via initial condensation of isat-
ins 3 with barbituric acids 1 to afford the Knoevenagel
12
product A, which then undergoes in situ Michael addi-
tion with anilines 2 (these electron-rich compounds act as
C-nucleophiles) followed by the cyclocondensation of the
intermediate B to give the corresponding products 4
2D NOESY experiment was carried out for 5c (see SI),
which exhibits strong cross-peaks between protons H-1
and H-7 as well as between H-10′ and H-9′, and H-10′ and
(
Scheme 1).
To expand the scope of the present reaction, isatin and its
-substituted derivatives were examined to replace N-
CH -1′, indicating that they are spatially close to each oth-
3
5
er (Figure 3). Moreover, the structures of compounds 5b
methyl- and N-ethylisatins. However, when the three-
component reaction of N-unsubstituted isatins, electron-
rich anilines and (thio)barbituric acids was conducted un-
(Figure 4) and 5f (Figure 5) were unambiguously con-
firmed by X-ray single crystal analysis. Recently, similar
transformation of the indolinone ring have been observed
der the same condition (ethanol, I , r.t., 24 h), isomeric
2
13
in the reaction of 6-aminouracils with isatins.
spiro[indole-3,5′-pyrimido[4,5-b]quinoline]-2,2′,4′-trione
Synthesis 2013, 45, 971–977
© Georg Thieme Verlag Stuttgart · New York

PAPER
Ring–Ring Transformation in Spirotriones
973
Table 1 Isomeric Spiro[indole-3,5′-pyrimido[4,5-b]quinoline]-2,2′,4′-triones 4a–k and 5a–n
Barbituric acid 1
Aniline 2
Isatin 3
Products 4 and 5
R1
X
R2
R3
R4
Isomer
Yield (%)a
Me
Me
Me
Me
Et
O
O
O
O
S
3,5-(MeO)2
H
Me
Me
Et
Et
Me
Me
Et
Et
Et
H
4a
86
3,4,5-(MeO)3
3,5-(MeO)2
H
4b
52
H
4c
82
3,4,5-(MeO)3
3,5-(MeO)2
H
4d
55
H
4e
56
Et
S
3,4,5-(MeO)3
3,5-(MeO)2
H
4f
47
Et
S
H
4g
72
Et
S
3,4,5-(MeO)3
2-anthraceneamine
3,5-(MeO)2
H
4h
47
Et
S
H
4i
73
H
O
O
O
O
O
O
O
S
H
5a
51
Me
Me
Me
Pr
3,5-(MeO)2
H
H
5b
57
3,5-(MeO)2
Cl
F
H
5c
72
3,5-(MeO)2
H
5d
75
3,5-(MeO)2
H
H
5e
79
Pr
3,4,5-(MeO)3
2-anthraceneamine
3,5-(MeO)2
H
H
5f
26
Pr
H
H
5g
91
Et
H
H
5h
81
Et
S
3,4,5-(MeO)3
3,5-(MeO)2
H
H
5i
53
Et
S
Cl
F
H
5j
68
Et
S
3,5-(MeO)2
H
5k
59
Et
S
3,4,5-(MeO)3
3,4,5-(MeO)3
3,5-(MeO)2
F
H
5l
36
Me
O
S
NO2
NO2
H
4j + 5m (85:15)
4k + 5n (25:75)
67/23b
63/19b
Et
H
a
Yields refer to pure isolated products.
Yield of isolated mixture/yield of the major isomer isolated in a pure state.
b
R4
7
7
1
N
1
MeO
MeO
H
6
6
7
NH
H
2
R2
2
1
N
5
O
5
O
R3
O
O
4
4
6
'
R1
6'
4'
R1
O
5
'
3
4'
3
N
2'
'
5'
3
3'
R3
7
'
N
2
O
R2
7'
8'
'
1
0'
10'
Cl
Me
8'
N
N1'
R1
X
N
N1'
R1
X
N
9
'
9'
H
H
10'
9'
N
N1'
O
4
5
H
H
Me
Figure 2 Isomers 4 and 5
5
c
Figure 3 Determination of regioisomer 5c by 2D NOESY (for the
original 2D NOESY spectra, see the Supporting Information); arrows
show the decisive correlations
©
Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 971–977

974
V. O. Iaroshenko et al.
PAPER
Table 2 The H and 13C NMR Data for Isomers 4 from 3,5-Dimethoxyaniline
1
Isomer 4
1H NMR, δ
13C NMR, δ
CH O-6′
CH O-8′
H-7′
H-9′
CH O-6′
CH O-8′
CH-7′
CH-9′
3
3
3
3
4
4
4
4
a
c
e
g
3.36
3.32
3.38
3.34
3.77
3.77
3.78
3.79
6.12
6.13
6.15
6.16
6.67
6.67
6.79
6.80
56.8
56.9
56.9
56.1
57.4
56.2
95.5
97.8
96.0
95.0
97.4
95.2
Table 3 The H and 13C NMR Data for Isomers 5 from 3,5-Dimethoxyaniline
1
Isomer 5
1H NMR, δ
13C NMR, δ
CH O-4
CH O-6
H-5
H-7
CH O-4
CH O-6
CH-5
CH-7
3
3
3
3
5
5
5
5
5
5
5
5
b
c
3.50
3.53
3.52
3.49
3.51
3.54
3.53
3.54
3.76
3.77
3.77
3.75
3.76
3.77
3.77
3.78
6.04
6.07
6.07
6.03
6.05
6.09
6.08
6.10
6.12
6.14
6.13
6.11
6.13
6.15
6.15
6.20
56.5
56.5
56.4
56.5
56.6
56.5
56.6
56.2
56.2
56.1
56.2
56.2
56.2
56.2
93.1
93.1
92.9
93.1
93.2
93.2
93.3
90.2
90.2
90.1
90.2
90.3
90.3
90.4
d
e
h
j
k
n
Table 4 The H and 13C NMR Data for Isomers 4 from 3,4,5-Trimethoxyaniline
1
Isomer 4
1H NMR, δ
13C NMR, δ
CH O-6′
CH O-7′
CH O-8′
H-9′
CH O-6′
CH O-7′
CH O-8′
CH-9′
3
3
3
3
3
3
4
4
4
4
4
b
d
f
3.12
3.03
3.14
3.04
3.27
3.60
3.60
3.61
3.61
3.62
3.83
3.83
3.85
3.85
3.85
6.93
6.92
6.97
7.05
6.96
60.4
60.1
60.4
60.2
60.4
61.2
61.1
61.2
61.1
61.2
56.6
56.6
56.7
56.7
56.7
97.2
97.2
97.5
97.5
97.3
h
j
Table 5 The H and 13C NMR Data for Isomers 5 from 3,4,5-Trimethoxyaniline
1
Isomer 5
1H NMR, δ
13C NMR, δ
CH O
CH O
CH O
H-7
CH O
CH O
CH O
CH-7
3
3
3
3
3
3
5
5
5
f
i
l
3.29
3.28
3.33
3.59
3.59
3.61
3.83
3.83
3.84
6.36
6.38
6.40
56.8
56.9
56.9
60.8
60.8
60.9
61.3
61.4
61.4
92.0
92.1
92.2
Synthesis 2013, 45, 971–977
© Georg Thieme Verlag Stuttgart · New York

PAPER
Ring–Ring Transformation in Spirotriones
975
tures 4j + 5m = 85:15 and 4k + 5n = 25:75 were obtained,
from which major isomers 4j and 5n were isolated in a
pure state (Table 1).
Next, attempts were made to replace isatins by other ac-
tive carbonyl compounds, such as chloral hydrate and eth-
yl pyruvate. When chloral hydrate was subjected to an
analogous reaction, the unexpected product 6 with a hy-
drolyzed trichloromethyl group from the four-component
reaction was obtained under the same conditions in 17%
yield. Fused 1,4-dihydropyridine 7, prepared from ethyl
pyruvate in 25% yield, is an unstable product and rear-
ranges slowly at room temperature under the action of at-
mospheric moisture to give quantitatively indolinone 8
(
Scheme 2). The structures of compounds 6–8 were char-
1
13
acterized by IR, H, C NMR spectral data as well as MS
and HRMS analyses. In addition, the structure of 8 is con-
14
firmed by X-ray diffraction analysis (Figure 6).
Figure 4 ORTEP plot of 4,6-dimethoxy-1′,3′-dimethyl-1′H-spi-
ro[indole-3,5′-pyrimido[4,5-b]quinoline]-2,2′,4′(1H,3′H,10′H)-tri-
one (5b) (thermal ellipsoids at 50% probability)
Figure 6 ORTEP plot of 5-(4,6-dimethoxy-3-methyl-2-oxo-2,3-di-
hydro-1H-indol-3-yl)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-tri-
one (8) (thermal ellipsoids at 50% probability)
Treatment of isatin with 3-benzylamino-5,5-dimethylcy-
clohex-2-enone resulted in the formation of 2-benzyl-4,4-
dimethyl-4,5-dihydropyrrolo[2,3,4-kl]acridin-1(2H)-one
(9) in 43% yield (Scheme 3). Very recently, this reaction
has been described for the three-component condensation
1
5
of isatin, dimedone, and various amines.
In conclusion, we have developed a novel and efficient
synthesis of spiroindolinones via a three-component reac-
tion between (thio)barbituric acids, electron-rich anilines,
and isatins. The described synthesis in ethanol media in
the presence of iodine is a simple, practical, and environ-
mentally friendly method for the preparation of heterocy-
Figure 5 ORTEP plot of 4,5,6-trimethoxy-1′,3′-dipropyl-1′H-spi-
ro[indole-3,5′-pyrimido[4,5-b]quinoline]-2,2′,4′(1H,3′H,10′H)-tri-
one (5f) (thermal ellipsoids at 50% probability)
As can be seen from Table 1, the reaction described has
virtually no limitations as regards the length of the alkyl
substituent in the (thio)barbituric molecule, but requires
N-unsubstituted isatins. This result and the absence of the
isomeric products 4 seem to indicate that the N-unsubsti-
tuted isatin fragment facilitates the rearrangement of
intermediate A into B toward formation of the thermody-
namically favored amide bond in spiroindolinone moiety
clic
compounds
containing
spiroindole-3,5′-
pyrimido[4,5-b]quinoline system, which undergoes an
unexpected recyclization related with the indolinone ring
opening in the case of N-unsubstituted isatins. On the oth-
er hand, the combinatorial aspect of the developed here
synthetic strategies can be used in the biology-oriented
syntheses; this investigations have already been started.
5
(Scheme 1). Only in the case of 5-nitroisatin the mix-
©
Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 971–977

976
V. O. Iaroshenko et al.
PAPER
O
OH
MeO
O
MeO
O
Me
O
N
Me
O
CCl3CH(OH)2
EtOH, I2
N
+
2
MeO
N
N
MeO
NH2
O
N
Me
O
Me
N
Me
N
O
Me
(17%)
EtOH, I2 MeCOCO2Et
6
Me
O
Me
O
N
O
CO2Et
O
N
N
MeO
O
N
O
Me
O
Me
Me
MeO
MeO
H2O
N
–
EtOH
MeO
N
H
N
O
CO2Et
O
N
H
Me
MeO
NH2
MeO
7
(25%)
8
(quant.)
Scheme 2 Synthesis of compounds 6–8
O
and EtOH (6 mL). I (0.096 mmol, 0.05 equiv) was then added and
the mixture was stirred overnight at r.t. The next day, the precipitate
2
O
that had formed was collected by filtration, washed with EtOH
O
+
(
2 × 3 mL), and recrystallized from an appropriate solvent, if neces-
N
NH
H
sary.
Bn
6
′,8′-Dimethoxy-1,1′,3′-trimethyl-1′H-spiro[indole-3,5′-pyrimi-
do[4,5-b]quinoline]-2,2′,4′ (1H,3′H,10′H)-trione (4a)
O
Bn
Yield: 716 mg (86%); white solid; mp >320 °C.
N
O
1
H NMR (300.1 MHz, DMSO-d ): δ = 3.01 (s, 3 H, NCH -3′), 3.20
HO
6
3
NH
(
3
s, 3 H, NCH -1), 3.36 (s, 3 H, CH O-6′), 3.55 (s, 3 H, NCH -1′),
3
3
3
4
4
.77 (s, 3 H, CH O-8′), 6.12 (d, J = 2.6 Hz, 1 H, H-7′), 6.67 (d, J =
3
O
3
N
2.6 Hz, 1 H, H-9′), 6.77–6.85 (m, 1 H, H-5), 6.85 (d, J = 7.2 Hz, 1
H, H-4), 6.88 (d, J = 7.7 Hz, 1 H, H-7), 7.13–7.20 (m, 1 H, H-6),
9
NH
Bn
3
9
(43%)
.17 (br s, 1 H, NH).
13
C NMR (62.9 MHz, DMSO-d ): δ = 27.1 (NCH -1), 28.3 (NCH -
6
3
3
H2N
3′), 31.1 (NCH -1′), 49.6 (C-3,5′), 56.1 (CH O-8′), 56.8 (CH O-6′),
3
3
3
O
O
87.2 (C-4a′), 95.0 (CH-9′), 95.5 (CH-7′), 105.2, 107.4 (CH ), 122.2
Ar
HO
(
CH ), 123.7 (CH ), 128.2 (CH ), 136.8, 138.1, 145.6, 146.2,
Ar Ar Ar
OH
O
NH
OH
151.2, 159.1, 160.1, 160.6, 179.8 (C=O-2).
+
+
N
Bn
N
MS (EI, 70 eV): m/z (%) = 435 ([M + H] , 14), 434 ([M] , 59), 406
Bn
(18), 376 (34), 375 (100), 318 (11), 44 (16).
+
HRMS (EI): m/z calcd for C H N O [M] : 434.15847; found:
23
22
4
5
Scheme 3 Synthesis of compound 9
4
34.15903.
7
′-Chloro-4,6-dimethoxy-1′,3′-dimethyl-1′H-spiro[indole-3,5′-
pyrimido[4,5-b]quinoline]-2,2′,4′ (1H,3′H,10′H)-trione (5c)
Yield: 627 mg (72%); white solid; mp >320 °C.
1
H NMR (300.1 MHz, DMSO-d ): δ = 3.08 (s, 3 H, NCH -3′), 3.53
All solvents were purified and dried by standard methods. NMR
spectra were recorded on a Bruker AV 300 and Bruker AV 400. IR
spectra were recorded on a PerkinElmer FT IR 1600 spectrometer
6
3
(
6
s, 3 H, CH O-4), 3.56 (s, 3 H, NCH -1′), 3.77 (s, 3 H, CH O-6),
3
3
3
4
4
.07 (d, J = 2.1 Hz, 1 H, H-5), 6.14 (d, J = 2.1 Hz, 1 H, H-7), 6.59
4
3
4
(
d, J = 2.5 Hz, 1 H, H-6′), 7.26 (dd, J = 8.7 Hz, J = 2.5 Hz, 1 H,
(
ATR). Mass spectra were obtained using a Hewlett-Packard HP
GC/MS 5890/5972 instrument (EI, 70 eV) by GC inlet or on a MX-
321 instrument (EI, 70 eV) by direct inlet. Column chromatogra-
3
H-8′), 7.34 (d, J = 8.7 Hz, 1 H, H-9′), 9.45 (br s, 1 H, NH-10′),
1
0.45 (br s, 1 H, NH-1).
1
13
phy was performed on silica gel (63–200 mesh, Merck). Silica gel
Merck 60F254 plates were used for TLC analysis. Chemical yields
refer to pure isolated substances.
C NMR (75.5 MHz, DMSO-d ): δ = 28.3 (NCH -3′), 31.0 (NCH -
6
3
3
1
(
(
′), 51.0 (C-3,5′), 56.2 (CH O-6), 56.5 (CH O-4), 84.6 (C-4a′), 90.2
3
3
CH-7), 93.1 (CH-5), 117.3, 119.4 (CH-9′), 125.0 (C-5a′), 125.9
CH-6′), 127.5, 128.7 (CH-8′), 135.9 (C-9a′), 143.7, 146.7, 151.3,
56.8, 160.3, 161.8, 181.3 (C=O-2).
Spiro[indole-3,5′-pyrimido[4,5-b]quinoline]-2,2′,4′-triones 4
and 5; General Procedure
Into a 25 mL flask were placed the corresponding barbituric acid 1
1
MS (GC, 70 eV): m/z (%) = 454 ([M]+, 35Cl, 35), 453 (27), 452
(1.92 mmol), isatin 3 (1.92 mmol), aromatic amine 2 (1.92 mmol),
(100), 423 (14), 421 (39), 412 (21), 411 (15), 410 (57), 290 (19),
2
89 (10), 288 (51).
Synthesis 2013, 45, 971–977
© Georg Thieme Verlag Stuttgart · New York

PAPER
HRMS (ESI): m/z calcd for C H ClN O [M + H] : 455.11167;
Ring–Ring Transformation in Spirotriones
977
35
20
+
1865. (d) Iaroshenko, V. O.; Wang, Y.; Zhang, B.;
22
4
5
found: 455.11218.
Volochnyuk, D.; Sosnovskikh, V. Y. Synthesis 2009, 2393.
e) Kotljarov, A.; Irgashev, R. A.; Iaroshenko, V. O.;
Sevenard, D. V.; Sosnovskikh, V. Y. Synthesis 2009, 3233.
f) Kotljarov, A.; Iaroshenko, V. O.; Volochnyuk, D. M.;
Irgashev, R. A.; Sosnovskikh, V. Y. Synthesis 2009, 3869.
g) Iaroshenko, V. O.; Ostrovskyi, D.; Petrosyan, A.;
Mkrtchyan, S.; Villinger, A.; Langer, P. J. Org. Chem. 2011,
6, 2899. (h) Iaroshenko, V. O.; Bunescu, A.; Spannenberg,
(
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis. Included
are experimental procedures, characterization data, and H,
NMR spectra of all compounds. SnuIpofopimngr irtSatnuIfiogop
(
1
13
C
(
r
t
ioarnt
7
A.; Langer, P. Chem. Eur. J. 2011, 17, 7188. (i) Iaroshenko,
V. O.; Mkrtchyan, S.; Villinger, A. Synthesis 2013, 45, 205.
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©
Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 971–977