A new four-component reaction for the synthesis of spiro[4H-indeno[1,2-b] pyridine-4,3′-[3H]indoles]

Article abstract of DOI:10.1002/hlca.201100047

A new four-component synthesis of spiro[4H-indeno[1,2-b]pyridine-4, 3′-[3H]indoles] and spiro[acenaphthylene-1(2H),4′-[4H-indeno[1,2-b] pyridines] by the reaction of indane-1,3-dione, 1,3-dicarbonyl compounds, isatins (=1H-indole-2,3-diones) or acenaphthy

Full text of DOI:10.1002/hlca.201100047

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Helvetica Chimica Acta – Vol. 94 (2011)
A New Four-Component Reaction for the Synthesis of Spiro[4H-indeno-
[1,2-b]pyridine-4,3’-[3H]indoles]
by Afsaneh Feiz, Ghazaleh Imani Shakibaei, Zahra Yasaei, Hamid Reza Khavasi, and Ayoob Bazgir*
Department of Chemistry, Shahid Beheshti University, G. C. Tehran, 1983963113, Iran
(e-mail: a_bazgir@sbu.ac.ir)
A new four-component synthesis of spiro[4H-indeno[1,2-b]pyridine-4,3’-[3H]indoles] and spiro-
[acenaphthylene-1(2H),4’-[4H-indeno[1,2-b]pyridines] by the reaction of indane-1,3-dione, 1,3-dicar-
bonyl compounds, isatins (¼1H-indole-2,3-diones) or acenaphthylene-1,2-dione, and AcONH4 in
refluxing toluene in the presence of a catalytic amount of pyridine is reported.
Introduction. – Multicomponent reactions (MCRs), due to their productivity,
simple procedures, convergence, and facile execution, are one of the best tools in
combinatorial chemistry [1]. Therefore, the design of novel MCRs has attracted great
attention from research groups working in areas such as drug discovery, organic
synthesis, and materials science. As a result, the number of new MCRs has grown
rapidly [2 – 6]. In the current work, we have elaborated a new four-component reaction
which gives wide access to spiro[indenopyridine-oxindole] products.
The heterocyclic 1H-indole and indoline (¼2,3-dihydro-1H-indole) ring system is a
widely distributed structural framework present in a number of pharmaceuticals and
natural products [7], and some indolines, spiro-annulated with heterocycles in the 3-
position, have shown high biological activity [8 – 11]. The spirooxindole system is the
core structure of many pharmacological agents and natural alkaloids (oxindole ¼ 1,3-
dihydro-2H-indol-2-one) [12 – 15]. Similarly, indenopyridine heterocycles represent
important biological and medicinal scaffolds. The indenopyridine skeleton is present in
the 4-azafluorenone group of alkaloids, represented by its simplest member onychnine
(Fig. 1) [16]. Indenopyridines A exhibit cytotoxic [17], phosphodiesterase inhibitory
[18], adenosine A2A receptor antagonistic [19], anti-inflammatory/anti-allergic [20],
coronary dilating [21], and calcium modulating activities [22]. Lastly, indenopyridone
Fig. 1. Representatives of important indenopyridines
ꢀ 2011 Verlag Helvetica Chimica Acta AG, Zꢁrich

Helvetica Chimica Acta – Vol. 94 (2011)
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NSC 314622 is serving as a lead compound for the development of anticancer agents
targeting topoisomerase I (Fig. 1) [23].
Although several isatin-based multicomponent reactions have been reported by our
research group [24 – 31] or other groups [11][32 – 36] leading to spirooxindole
containing heterocycles, reactions of indane-1,3-dione (¼1H-indene-1,3(2H)-dione),
isatin (¼1H-indole-2,3-dione), a 1,3-dicarbonyl compound, and AcONH4 have not
been reported yet. In this article, we report for the first time the synthesis of spiro[4H-
indeno[1,2-b]pyridine-4,3’-[3H]indoles] 4 based on a one-pot four-component reaction
of indane-1,3-dione (1), isatins 2, 1,3-dicarbonyl compounds 3, and AcONH4
(Scheme 1).
Scheme 1
Results and Discussion. – A mixture of 1, an isatin 2a – 2j, a 1,3-dicarbonyl
compound 3a – 3e, and AcONH4 in the presence of a catalytic amount (15 mol-%) of
pyridine in refluxing toluene, afforded after 24 h, spiro[4H-indeno[1,2-b]pyridine-4,3’-
[3H]indoles] 4a – 4z in good yields (Scheme 1). The results were good in terms of yields
(Table 1) and product purity in the presence of pyridine, while in the absence of
pyridine, the yields were low (<40%) even after 48 h.
The structures of the isolated products 4a – 4z were deduced from their elemental
analyses and IR and 1H-, and 13C-NMR spectra. The mass spectra of these compounds
displayed molecular-ion peaks at the appropriate m/z values. The structure of 4t was
established by a single-crystal X-ray diffraction analysis (Fig. 2).
The mass spectrum of 4a (X ¼ R ¼ H, R1 ¼ Me, R2 ¼ MeO) showed the molecular-
ion peak at m/z 372. The IR spectrum exhibited absorption bands for the C¼O groups
at 1697, 1674, and 1641 cmꢀ1, and for two NH groups at 3247 and 3153 cmꢀ1. In the
1H-NMR spectrum of 4a, four sharp ss for a Me group (d(H) 2.42), a MeO group
(d(H) 3.30), and two NH groups (d(H) 10.28 and 10.37) appeared, along with ms
(d(H) 6.74 – 7.65) for the aromatic H-atoms. The 1H-decoupled 13C-NMR spectra of 4a
exhibited 22 distinct resonances that confirm the proposed structures. The character-

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Helvetica Chimica Acta – Vol. 94 (2011)
Table 1. Synthesis of Spiro[4H-indeno[1,2-b]pyridine-4,3’-[3H]indolines 4
X
R
R1
R2
Yield [%]a)
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4q
4r
H
H
H
H
H
H
H
H
H
H
H
Br
Br
Br
NO2
NO2
NO2
NO2
Br
Br
Br
Br
NO2
NO2
NO2
NO2
H
H
H
H
Me
Me
Me
Et
Et
Bn
Bn
H
H
H
H
H
H
H
Me
Me
Et
Et
Me
Me
Et
Et
Me
Me
Me
Pr
Me
Me
Pr
MeO
EtO
Me
85
79
80
80
87
80
76
75
78
80
83
92
88
82
90
91
91
85
76
87
78
80
84
89
85
88
EtO
MeO
EtO
EtO
MeO
EtO
MeO
EtO
MeO
EtO
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Pr
Me
Me
Me
Me
Me
Me
Me
Me
MeO
EtO
Me
EtO
MeO
EtO
MeO
EtO
MeO
EtO
MeO
EtO
4s
4t
4u
4v
4w
4x
4y
4z
a) Yield of isolated product.
istic C-atom signals of 4a were attributed to Me, MeO, Cspiro, CONH, CO2Me, and
C¼O, and they appeared at d 19.7, 50.0, 51.1, 166.6, 179.9, and 189.6.
To the best of our knowledge, this new procedure provides the first example of a
four-component synthesis of spiro[indenopyridine-oxindoles]. In addition, the workup
of these very clean reactions involves only a filtration and simple washing step with
MeOH.
We have not established an exact mechanism for the formation of 4, however, it can
be rationalized by the initial formation of intermediate 5 via condensation of 1 and 2.
Then, 5 is attacked by enamine 6 (formed in situ by the reaction of 3 with AcONH4), in
a Michael fashion to produce intermediate 7. Finally, product 4 is obtained via an
intramolecular cyclocondensation in 75 – 92% yield (Scheme 2). From a mechanistic
view point, it is notable that indane-1,3-dione 1, enamines 6a,b, and isatin (2a) reacted
under the same reaction conditions to 4a,b in good yields.
As expected, when isatin 2 was replaced by acenaphthylene-1,2-dione (8),
spiro[acenaphthylene-1(2H),4’-[4H-indeno[1,2-b]pyridines] 9 were obtained in 75 –
80 yield under the same reaction conditions (Scheme 3).
In summary, we have developed a one-pot four-component reaction for the
preparation of spiro[4H-indeno[1,2-b]pyridine-4,3’-[3H]indoles] and spiro[acenaph-

Helvetica Chimica Acta – Vol. 94 (2011)
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Fig. 2. X-Ray crystal structure of 4t (X ¼ Br, R ¼ R1 ¼ Me, R2 ¼ EtO). 50% Probability ellipsoids,
arbitrary atom numbering
Scheme 2

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Helvetica Chimica Acta – Vol. 94 (2011)
Scheme 3
thylene-1(2H),4’-[4H-indeno[1,2-b]pyridines] of potential synthetic and biological
interest. The method is simple, starts from readily accessible commercial reagents, and
provides biologically interesting spirooxindol derivatives in good yields.
Experimental Part
General. The chemicals used in this work were obtained from Fluka and Merck and were used
without purification. Melting points (M.p.): Electrothermal 9100 apparatus; uncorrected. IR Spectra:
1
Bomem MB-series FT-IR spectrometer; in cmꢀ1. H- and 13C-NMR Spectra: Bruker-DRX-300-Avance
spectrometer; at 300.13 (1H) and 75.47 MHz (13C); in (D6)DMSO; d in ppm rel. to Me4Si as internal
standard, J in Hz. EI-MS (70 eV): Finnigan-MAT-8430 mass spectrometer; in m/z. Elemental analyses:
Heraeus-CHN-O-Rapid analyzer.
Methyl 1,1’,2’,5-Tetrahydro-2-methyl-2’,5-dioxospiro[4H-indeno[1,2-b]pyridine-4,3’-[3H]indole]-3-
carboxylate (4a): Typical Procedure. A mixture of indane-1,3-dione (1; 1 mmol), isatin (2a; 1 mmol),
methyl acetoacetate (¼ methyl 3-oxobutanoate; 3a; 1 mmol), AcONH4 (1.5 mmol), and pyridine
(15 mol-%) in refluxing toluene (5 ml) was stirred for 24 h. After completion of the reaction (TLC
(AcOEt/hexane 2 :1) monitoring, the mixture was cooled to r.t. and the precipitated product filtered and
washed with H2O (10 ml) and MeOH (5 ml): pure 4a (0.31 g, 85%). Red powder. M.p. > 3008. IR (KBr):
1
3247, 3153, 1697, 1674, 1641. H-NMR: 2.42 (s, Me); 3.30 (s, MeO); 6.74 – 7.65 (m, 8 H); 10.28 (s, NH);
10.37 (s, NH). 13C-NMR: 19.7; 50.0; 51.1; 105.8; 107.1; 109.0; 120.0; 121.0; 121.6; 123.7; 128.3; 130.9;
132.4; 133.4; 135.9; 136.8; 142.7; 146.9; 154.0; 166.6; 179.9; 189.6. EI-MS: 372 (Mþ). Anal. calc. for
C22H16N2O4 (372.38): C 70.96, H 4.33, N 7.52; found: C 70.91, H 4.28, N 7.47.
Ethyl 1,1’,2’,5-Tetrahydro-2-Methyl-2’,5-dioxospiro[4H-indeno[1,2-b]pyridine-4,3’-[3H]indole]-3-
carboxylate (4b). Yield 79%. Red powder. M.p. > 3008. IR (KBr): 3211, 3158, 1680, 1638, 1617.
1H-NMR: 0.81 (t, J ¼ 6.3, Me); 2.42 (s, Me); 3.72 – 3.74 (m, CH2O); 6.73 – 7.64 (m, 8 H); 10.29 (s, NH);
10.38 (s, NH). 13C-NMR: 13.5; 19.5; 49.9; 57.3; 105.6; 107.1; 109.0; 119.9; 121.0; 121.6; 123.8; 128.2; 130.9;
132.4; 133.4; 135.9; 137.0; 142.8; 147.0; 154.0; 166.1; 180.0; 189.7. EI-MS: 386 (Mþ). Anal. calc. for
C23H18N2O4 (386.40): C 71.49, H 4.70, N 7.25; found: C 71.42, H 4.75, N 7.18.
3-Acetyl-2-methylspiro[4H-indeno[1,2-b]pyridine-4,3’-[3H]indole]-2’,5(1H,1’H)-dione (4c). Yield
80%. Orange powder. M.p. > 3008. IR (KBr): 3251, 3165, 1691, 1640, 1619. 1H-NMR: 2.09 (s, Me);
2.39 (s, Me); 6.71 – 7.60 (m, 8 H); 10.28 (s, 2 NH). 13C-NMR: 20.1; 32.2; 50.4; 107.0; 109.1; 119.9; 120.9;
121.6; 123.6; 125.8; 128.7; 129.3; 130.8; 132.3; 133.5; 135.9; 136.5; 142.7; 144.2; 154.1; 179.7; 197.8. EI-MS:
356 (Mþ). Anal. calc. for C22H16N2O3 (356.37): C 74.15, H 4.53, N 7.86; found: C 74.07, H 4.48, N 7.80.
Ethyl 1,1’,2’,5-Tetrahydro-2’,5-dioxo-2-propylspiro[4H-indeno[1,2-b]pyridine-4,3’-[3H]indole]-3-
1
carboxylate (4d). Yield 80%. Red powder. M.p. > 3008. IR (KBr): 3216, 3190, 1690, 1648. H-NMR:
0.83 (t, J ¼ 6.9, Me); 1.00 (s, J ¼ 7.2, Me); 1.69 (q, J ¼ 7.2, CH2); 2.53 – 2.88 (m, CH2); 3.74 (q, J ¼ 6.9,
CH2O); 6.73 – 7.67 (m, 8 H); 10.26 (s, NH); 10.28 (s, NH). 13C-NMR: 13.5; 14.1; 22.6; 33.9; 49.9; 60.0;
105.6; 106.7; 109.1; 120.1; 120.9; 121.7; 123.6; 128.2; 130.9; 132.3; 133.5; 135.9; 136.9; 142.8; 150.7; 154.2;

Helvetica Chimica Acta – Vol. 94 (2011)
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165.8; 180.0; 189.5. EI-MS: 414 (Mþ). Anal. calc. for C25H22N2O4 (414.45): C 72.45, H 5.35, N 6.76; found:
C 72.52, H 5.39, N 6.70.
Methyl 1,1’,2’,5-Tetrahydro-1’,2-dimethyl-2’,5-dioxospiro[4H-indeno[1,2-b]pyridine-4,3’-[3H]in-
dole]-3-carboxylate (4e). Yield 87%. Brown powder. M.p. > 3008. IR (KBr): 3252, 1701, 1674, 1654.
1H-NMR: 2.43 (s, Me); 3.15 (s, MeN); 3.27 (s, MeO); 6.88 – 7.65 (m, 8 H); 10.43 (s, NH). 13C-NMR: 19.7;
26.7; 49.4; 51.3; 105.4; 107.0; 107.9; 120.1; 121.0; 122.4; 123.5; 128.5; 131.0; 132.5; 133.4; 135.9; 136.0;
144.1; 147.5; 154.0; 166.5; 178.4; 189.6. EI-MS: 386 (Mþ). Anal. calc. for C23H18N2O4 (386.40): C 71.49, H
4.70, N 7.25; found: C 71.39, H 4.77, N 7.17.
Ethyl 1,1’,2’,5-Tetrahydro-1’,2-dimethyl-2’,5-dioxospiro[4H-indeno[1,2-b]pyridine-4,3’-[3H]indole]-
1
3-carboxylate (4f). Yield 80%. Red powder. M.p. > 3008. IR (KBr): 3164, 1680, 1647, 1610. H-NMR:
0.74 (t, J ¼ 6.9, Me); 2.45 (s, Me); 3.15 (s, MeN); 3.68 – 3.73 (m, CH2O); 6.87 – 7.645 (m, 8 H); 10.44 (s,
NH). 13C-NMR: 13.8; 19.6; 26.6; 49.4; 59.8; 105.0; 107.1; 107.8; 120.1; 121.0; 122.4; 123.5; 128.4; 130.9;
132.4; 133.4; 135.9; 136.2; 144.2; 147.7; 153.9; 165.9; 178.3; 189.6. EI-MS: 400 (Mþ). Anal. calc. for
C24H20N2O4 (400.43): C 71.99, H 5.03, N 7.00; found: C 71.93, H 4.98, N 6.95.
Ethyl 1,1’,2’,5-Tetrahydro-1’-methyl-2’,5-dioxo-2-propylspiro[4H-indeno[1,2-b]pyridine-4,3’-[3H]-
indole]-3-carboxylate (4g). Yield 76%. Red powder. M.p. > 3008. IR (KBr): 3158, 1690, 1669, 1643.
1H-NMR: 0.74 (br. s, Me); 1.01 (br. s, Me); 1.69 (br. s, CH2); 2.75 – 2.82 (m, CH2); 3.14 (s, Me); 3.69 – 3.71
(m, CH2O); 6.90 – 7.68 (m, 8 H); 10.35 (s, NH). 13C-NMR: 13.7; 14.1; 22.6; 26.6; 34.0; 49.5; 59.9; 105.1;
106.8; 107.9; 120.2; 120.9; 122.4; 123.3; 128.4; 130.9; 132.4; 133.4; 135.9; 136.2; 144.2; 151.4; 154.1; 165.7;
178.3; 189.5. EI-MS: 428 (Mþ). Anal. calc. for C26H24N2O4 (428.48): C 72.88, H 5.65, N 6.54; found: C
72.82, H 5.59, N 6.50.
Methyl 1’-Ethyl-1,1’,2’,5-tetrahydro-2-methyl-2’,5-dioxospiro[4H-indeno[1,2-b]pyridine-4,3’-[3H]-
indole]-3-carboxylate (4h). Yield 75%. Orange powder. M.p. > 3008. IR (KBr): 3247, 1695, 1679.
1H-NMR: 1.22 (t, J ¼ 6.9, Me); 2.44 (s, Me); 3.26 (s, MeO); 3.72 (q, J ¼ 6.9, CH2N); 6.88 – 7.65 (m, 8 H);
10.42 (s, NH). 13C-NMR: 12.7; 19.7; 34.6; 49.4; 51.1; 105.3; 107.1; 107.9; 120.1; 121.0; 122.1; 123.7; 128.4;
130.9; 132.4; 133.4; 135.9; 136.2; 143.0; 147.5; 154.0; 166.5; 177.7; 189.6. EI-MS: 400 (Mþ). Anal. calc. for
C24H20N2O4 (400.43): C 71.99, H 5.03, N 7.00; found: C 71.90, H 5.10, N 7.06.
Ethyl 1’-Ethyl-1,1’,2’,5-tetrahydro-2-methyl-2’,5-dioxospiro[4H-indeno[1,2-b]pyridine-4,3’-[3H]-
indole]-3-carboxylate (4i). Yield 78%. Red powder. M.p. > 3008. IR (KBr): 3153, 1711, 1674, 1643.
1H-NMR: 0.72 (t, J ¼ 6.9, Me); 1.23 (t, J ¼ 6.3, Me); 2.44 (s, Me); 3.57 – 3.68 (m, CH2N); 3.70 – 3.78 (m,
CH2O); 6.88 – 7.65 (m, 8 H); 10.41 (s, NH). 13C-NMR: 12.6; 13.7; 19.6; 34.2; 49.5; 59.7; 105.1; 107.1; 107.9;
120.0; 121.0; 122.1; 123.6; 128.4; 130.9; 132.4; 133.4; 135.9; 136.3; 143.2; 147.6; 153.9; 165.9; 177.7; 189.6.
EI-MS: 414 (Mþ). Anal. calc. for C25H22N2O4 (414.45): C 72.45, H 5.35, N 6.76; found: C 72.52, H 5.39, N
6.71.
Methyl 1’-Benzyl-1,1’,2’,5-tetrahydro-2-methyl-2’,5-dioxospiro[4H-indeno[1,2-b]pyridine-4,3’-[3H]-
indole]-3-carboxylate (4j). Yield 80%. Orange powder. M.p. > 3008. IR (KBr): 3247, 1731, 1679, 1653.
1H-NMR: 2.47 (s, Me); 3.13 (s, MeO); 4.78, 5.04 (AB(q), J ¼ 15.9, CH2N); 6.73 – 7.78 (m, 13 H); 10.42 (s,
NH). 13C-NMR: due to very low solubility, no data. EI-MS: 462 (Mþ). Anal. calc. for C29H22N2O4
(462.50): C 75.31, H 4.79, N 6.06; found: C 75.26, H 4.73, N 6.14.
Ethyl 1’-Benzyl-1,1’,2’,5-tetrahydro-2-methyl-2’,5-dioxospiro[4H-indeno[1,2-b]pyridine-4,3’-[3H]-
indole]-3-carboxylate (4k). Yield 83%. Brown powder. M.p. > 3008. IR (KBr): 3216, 1716, 1685, 1654.
1H-NMR: 0.62 (t, J ¼ 6.9, Me); 2.50 (s, Me); 3.46 – 3.83 (m, CH2O); 4.67, 4.93 (AB(q), J ¼ 15.9, CH2N);
6.72 – 7.68 (m, 13 H); 10.48 (s, NH). 13C-NMR: 13.8; 19.7; 44.3; 49.5; 59.8; 105.6; 106.7; 108.6; 120.1;
121.2; 122.5; 123.7; 127.6; 128.1; 128.3; 128.8; 131.0; 131.6; 132.5; 133.4; 135.9; 136.1; 137.1; 143.6; 147.3;
154.3; 166.0; 178.6; 189.7. EI-MS: 476 (Mþ). Anal. calc. for C30H24N2O4 (476.52): C 75.61, H 5.08, N 5.88;
found: C 75.50, H 5.01, N 5.84.
Methyl 5’-Bromo-1,1’,2’,5-tetrahydro-2-methyl-2’,5-dioxospiro[4H-indeno[1,2-b]pyridine-4,3’-[3H]-
indole]-3-carboxylate (4l). Yield 92%. Orange powder. M.p. > 3008. IR (KBr): 3216, 3158, 1700, 1679,
1637. 1H-NMR: 2.43 (s, Me); 3.16 (s, MeO); 6.71 – 7.66 (m, 7 H); 10.44 (s, 2 NH). 13C-NMR: 19.8; 49.0;
50.2; 51.2; 105.0; 106.5; 110.9; 113.2; 120.2; 121.1; 126.5; 131.0; 132.5; 133.3; 135.9; 139.3; 142.1; 147.9;
154.2; 166.5; 179.5; 189.7. EI-MS: 452 (M þ 2), 450 (Mþ). Anal. calc. for C22H15BrN2O4 (451.27): C 58.55,
H 3.35, N 6.21; found: C 58.48, H 3.39, N 6.16.

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Ethyl 5’-Bromo-1,1’,2’,5-tetrahydro-2-methyl-2’,5-dioxospiro[4H-indeno[1,2-b]pyridine-4,3’-[3H]in-
dole]-3-carboxylate (4m). Yield 88%. Red powder. M.p. > 3008. IR (KBr): 3164, 1695, 1674, 1643.
1H-NMR: 0.86 (t, J ¼ 6.9, Me); 2.50 (s, Me); 3.77 – 3.79 (m, CH2O); 6.71 – 7.66 (m, 7 H); 10.45 (s, NH).
13C-NMR: 13.6; 19.7; 50.2; 60.1; 104.8; 106.5; 111.0; 113.2; 120.2; 121.1; 126.5; 130.9; 131.0; 132.4; 133.4;
135.9; 139.4; 142.3; 148.0; 154.2; 165.9; 179.6; 189.6. EI-MS: 466 (M þ 2), 464 (Mþ). Anal. calc. for
C23H17BrN2O4 (465.30): C 59.37, H 3.68, N 6.02; found: C 59.30, H 3.62, N 6.09.
3-Acetyl-5’-bromo-2-methylspiro[4H-indeno[1,2-b]pyridine-4,3’-[3H]indole]-2’,5(1H,1’H)-dione
(4n). Yield 82%. Orange powder. M.p. > 3008. IR (KBr): 3252, 3160, 1698, 1678, 1639. 1H-NMR: 2.09 (s,
Me); 2.47 (s, Me); 6.68 – 7.67 (m, 7 H); 10.35 (s, NH); 10.39 (s, NH). 13C-NMR: 20.4; 46.4; 50.7; 109.4;
110.9; 113.1; 117.2; 120.4; 121.1; 124.3; 126.1; 131.0; 132.4; 133.4; 134.4; 135.9; 139.1; 142.2; 146.0; 154.2;
179.4; 197.2. EI-MS: 436 (M þ 2), 434 (Mþ). Anal. calc. for C22H15BrN2O3 (435.27): C 60.71, H 3.47, N
6.44; found: C 60.65, H 3.42, N 6.36.
Methyl 1,1’,2’,5-Tetrahydro-2-methyl-5’-nitro-2’,5-dioxospiro[4H-indeno[1,2-b]pyridine-4,3’-[3H]in-
dole]-3-carboxylate (4o). Yield 90%. Red powder. M.p. > 3008. IR (KBr): 3179, 3221, 1712, 1674,
1641. 1H-NMR: 2.29 (s, Me); 3.36 (s, MeO); 6.97 – 8.13 (m, 7 H); 10.59 (s, NH); 11.08 (s, NH). 13C-NMR:
20.0; 50.1; 51.4; 104.4; 109.1; 119.2; 120.5; 121.2; 125.8; 126.0; 128.6; 129.4; 131.2; 132.6; 133.2; 135.8;
137.8; 142.4; 148.9; 149.4; 166.4; 180.5. EI-MS: 417 (Mþ). Anal. calc. for C22H15N3O6 (417.37): C 63.31, H
3.62, N 10.07; found: C 63.40, H 3.68, N 10.02.
Ethyl 1,1’,2’,5-Tetrahydro-2-methyl-5’-nitro-2’,5-dioxospiro[4H-indeno[1,2-b]pyridine-4,3’-[3H]in-
dole]-3-carboxylate (4p). Yield 91%. Red powder. M.p. > 3008. IR (KBr): 3247, 3169, 1711, 1680, 1643
. 1H-NMR: 0.87 (t, J ¼ 6.9, Me); 2.55 (s, Me); 3.79 (q, J ¼ 6.9, CH2O); 6.97 – 8.16 (m, 7 H); 10.60 (s, NH);
11.10 (s, NH). 13C-NMR: 13.9; 19.9; 49.4; 60.2; 103.6; 105.8; 108.1; 118.8; 120.5; 121.3; 126.1; 131.2; 132.7;
133.2; 135.8; 137.1; 143.0; 149.6; 150.2; 154.5; 165.6; 179.1; 189.7. EI-MS: 431 (Mþ). Anal. calc. for
C23H17N3O6 (431.40): C 64.04, H 3.97, N 9.74; found: C 63.97, H 3.82, N 9.80.
3-Acetyl-2-methyl-5’-nitrospiro[4H-indeno[1,2-b]pyridine-4,3’-[3H]indole]-2’,5(1H,1’H)-dione (4q).
Yield 91%. Orange powder. M.p. > 3008. IR (KBr): 3247, 1744, 1707, 1641. 1H-NMR: 2.24 (s, Me); 2.55
(s, Me); 6.92 – 7.79 (m, 7 H); 10.49 (s, NH); 11.00 (s, NH). 13C-NMR: due to very low solubility, no data.
EI-MS: 401 (Mþ). Anal. calc. for C22H15N3O5 (401.37): C 65.83, H 3.77, N 10.47; found: C 65.71, H 3.70, N
10.39.
Ethyl 1,1’,2’,5’-Tetrahydro-5’-nitro-2’,5-dioxo-2-propylspiro[4H-indeno[1,2-b]pyridine-4,3’-[3H]in-
dole]-3-carboxylate (4r). Yield 85%. Red powder. M.p. > 3008. IR (KBr): 3143, 3070, 1721, 1669,
1638. 1H-NMR: 0.88 (t, J ¼ 6.6, Me); 1.02 (s, J ¼ 6.9, Me); 1.70 – 1.72 (m, CH2); 2.83 (m, CH2); 3.79 – 3.81
(m, CH2); 6.97 – 8.14 (m, 7 H); 10.51 (s, NH); 11.07 (s, NH). 13C-NMR: due to very low solubility, no
data. EI-MS: 459 (Mþ). Anal. calc. for C25H21N3O6 (459.45): C 65.35, H 4.61, N 9.15; found: C 65.42, H
4.56, N 9.06.
Methyl 5’-Bromo-1,1’,2’,5-tetrahydro-1’,2-dimethyl-2’,5-dioxospiro[4H-indeno[1,2-b]pyridine-4,3’-
[3H]indole]-3-carboxylate (4s). Yield 76%. Orange powder. M.p. > 3008. IR (KBr): 3148, 1676, 1644.
1H-NMR: 2.44 (s, Me); 3.16 (s, MeN); 3.30 (s, MeO); 6.71 – 7.66 (m, 7 H); 10.45 (s, 2 NH). 13C-NMR:
19.9; 49.1; 50.2; 51.3; 105.0; 106.5; 110.9; 113.2; 120.2; 121.1; 123.2; 126.5; 131.0; 132.5; 133.3; 135.9; 139.3;
142.1; 147.9; 154.2; 166.5; 179.6; 189.6. EI-MS: 466 (M þ 2), 464 (Mþ). Anal. calc. for C23H17BrN2O4
(465.30): C 59.37, H 3.68, N 6.02; found: C 59.32, H 3.64, N 5.96.
Ethyl 5’-Bromo-1,1’,2’,5-tetrahydro-1’,2-dimethyl-2’,5-dioxospiro[4H-indeno[1,2-b]pyridine-4,3’-
[3H]indole]-3-carboxylate (4t). Yield 87%. Orange powder. M.p. > 3008. IR (KBr): 3161, 1717, 1681,
1647. 1H-NMR: 0.80 (t, J ¼ 6.3, Me); 2.48 (s, Me); 3.15 (s, MeN); 3.75 (q, J ¼ 6.9, CH2O); 6.94 – 7.68 (m,
7 H); 10.53 (s, NH). 13C-NMR: 13.8; 19.8; 267; 49.6; 60.0; 104.3; 106.4; 109.9; 114.1; 120.3; 121.1; 124.4;
126.3; 131.1; 132.5; 133.3; 135.8; 138.5; 143.6; 148.7; 154.2; 165.8; 177.9; 189.6. EI-MS: 480 (M þ 2), 478
(Mþ). Anal. calc. for C24H19BrN2O4 (479.31): C 60.14, H 4.00, N 5.84; found: C 60.01, H 4.07, N 5.90.
X-Ray Crystal Structure of 4t1). The X-ray diffraction measurements was made with a Stoe-IPDS-II
diffractometer and graphite-monochromated MoKa radiation. A red prism crystal with a dimension of
0.10 ꢁ 0.16 ꢁ 0.21 nm was mounted on a glass fiber and used for data collection. Cell constants and an
1
)
CCDC-810504 contains the supplementary crystallographic data for 4t. These data can be obtained
free of charge via http://www.ccdc.cam.ac.uk/data_request/cif.

Helvetica Chimica Acta – Vol. 94 (2011)
1635
orientation matrix for data collection were obtained by least-squares refinement of diffraction data from
5604 unique reflections. Data were collected at 298(2) K to a maximum 2q value of 58.428 and in a series
of w scans in 18 oscillations and integrated by using the Stoe X-AREA [37] software package. The
numerical absorption coefficients, m, for MoKa radiation is 2.001 mmꢀ1. A numerical absorption
correction was applied with X-RED [38] and X-SHAPE [39] softwares. The data were corrected for
Lorentz and polarizing effects. The structure was solved by direct methods and subsequent differences
Fourier map and then refined on F2 by a full-matrix least-squares procedure by using anisotropic
displacement parameters [40]. All H-atoms were added at ideal positions and constrained to ride on their
parent atoms, with Uiso(H) ¼ 1.2 Ueq. All refinements were performed with the X-STEP32 crystallo-
graphic software package [41]. A summary of the crystal data, experimental details, and refinement
results is given in Table 2.
Table 2. Crystallographic and Structure Refinements Data of 4t
Empirical formula
Mr
C24H19BrN2O4
479.31
298(2)
V [ꢂ3]
Z
1045.4(3)
2
1.523
1.75 – 29.21
488
2.001
ꢀ 10 ꢂ h ꢂ 10,
ꢀ 15 ꢂ k ꢂ 14,
ꢀ 15 ꢂ l ꢂ 17
12029
5604, (0.145)
280, 0
0.1091, 0.2255
1.141
0.63; ꢀ 0.58
Temperature [K]
Wavelength l [ꢂ]
Crystal system
Space group
Crystal size [mm3]
Unit cell parameters:
a [ꢂ]
b [ꢂ]
c [ꢂ]
a [8]
b [8]
Dx [g cmꢀ3
]
0.71073
q Ranges for data collection
F(000)
Absorption coefficient [mmꢀ1
Index ranges
triclinic
¯
P1
]
0.10 ꢁ 0.16 ꢁ 0.21
7.9438(15)
11.310(2)
12.976(2)
70.503(14)
72.368(14)
87.320(16)
Data collected
Unique data (Rint
)
Parameters, restrains
Final R1, wR2a) (obs. data)
Goodness of fit on F2 (S)
g [8]
Largest diff. peak and hole [e ꢂꢀ3
]
a) R1 ¼ S jj Fo jꢀj Fc jj /S j Fo j , wR2 ¼ [S(w(Fo2 ꢀ F2c )2)/Sw(Fo2 )2]1/2
.
Methyl 5’-Bromo-1’-ethyl-1,1’,2’,5-tetrahydro-2-methyl-2’,5-dioxospiro[4H-indeno[1,2-b]pyridine-
4,3’-[3H]indole]-3-carboxylate (4u). Yield 78%. Orange powder. M.p. > 3008. IR (KBr): 3210, 1716,
1683, 1646. 1H-NMR: 1.20 (t, J ¼ 6.0, Me); 2.45 (s, Me); 3.30 (s, MeO); 3.71 (q, J ¼ 6.0, CH2N); 6.95 – 7.67
(m, 7 H); 10.50 (s, NH). 13C-NMR: 12.5; 19.9; 33.4; 49.6; 51.2; 104.5; 106.4; 109.9; 113.8; 120.2; 121.2;
126.4; 131.0; 132.5; 133.3; 135.9; 136.1; 138.6; 142.5; 148.5; 154.2; 166.4; 177.3; 1896. EI-MS: 480 (M þ 2),
478 (Mþ). Anal. calc. for C24H19BrN2O4 (479.32): C 60.14, H 4.00, N 5.84; found: C 60.06, H 3.93, N 5.76.
Ethyl 5’-Bromo-1’-ethyl-1,1’,2’,5-tetrahydro-2-methyl-2’,5-dioxospiro[4H-indeno[1,2-b]pyridine-4,3’-
[3H]indole]-3-carboxylate (4v). Yield 80%. Orange powder. M.p. > 3008. IR (KBr): 3153, 1716, 1685,
1643. 1H-NMR: 0.78 (t, J ¼ 6.9, Me); 1.22 (t, J ¼ 6.6, Me); 2.47 (s, Me); 3.59 – 3.81 (m, 2 CH2); 6.94 – 7.69
(m, 7 H); 10.50 (s, NH). 13C-NMR: 12.1; 13.5; 19.5; 34.3; 49.6; 59.7; 104.3; 106.3; 113.8; 120.1; 126.4;
129.1; 130.8; 130.9; 132.2; 133.3; 135.8; 136.5; 138.7; 142.5; 148.5; 154.2; 165.7; 177.5; 189.7. EI-MS: 494
(M þ 2), 492 (Mþ). Anal. calc. for C25H21BrN2O4 (493.35): C 60.86, H 4.29, N 5.68; found: C 60.81, H 4.33,
N 5.61.
Methyl 1,1’,2’,5-Tetrahydro-1’,2-dimethyl-5’-nitro-2’,5-dioxospiro[4H-indeno[1,2-b]pyridine-4,3’-
[3H]indole]-3-carboxylate (4w). Yield 84%. Orange powder. M.p. > 3008. IR (KBr): 3153, 1685, 1648.
1H-NMR: 2.48 (s, Me); 3.27 (s, MeN); 3.34 (s, MeO); 7.17 – 8.23 (m, 7 H); 10.65 (s, NH). 13C-NMR: 20.0;
27.1; 49.4; 51.6; 104.0; 108.1; 111.4; 118.8; 120.6; 121.3; 125.3; 126.1; 131.2; 132.7; 133.2; 137.0; 143.0;
146.8; 149.3; 150.2; 154.6; 166.3; 179.1. EI-MS: 431 (Mþ). Anal. calc. for C23H17N3O6 (431.40): C 64.04, H
3.97, N 9.74; found: C 64.13, H 3.91, N 9.81.

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Helvetica Chimica Acta – Vol. 94 (2011)
Ethyl 1,1’,2’,5-Tetrahydro-1’,2-dimethyl-5’-nitro-2’,5-dioxospiro[4H-indeno[1,2-b]pyridine-4,3’-
[3H]indole]-3-carboxylate (4x). Yield 89%. Orange powder. M.p. > 3008. IR (KBr): 3174, 1695, 1648.
1H-NMR: 0.80 (t, J ¼ 6.9, Me); 2.51 (s, Me); 3.26 (s, MeN); 3.76 (q, J ¼ 6.9, CH2O); 7.17 – 8.26 (m, 7 H);
10.66 (s, NH). 13C-NMR: 13.6; 19.9; 27.0; 49.4; 60.2; 103.6; 105.8; 108.1; 118.8; 120.5; 121.2; 126.1; 131.2;
132.6; 133.2; 135.7; 137.1; 143.0; 149.6; 150.2; 154.5; 165.6; 179.1; 189.7. EI-MS: 445 (Mþ). Anal. calc. for
C24H19N3O6 (445.42): C 64.72, H 4.30, N 9.43; found: C 64.63, H 4.25, N 9.36.
Methyl 1’-Ethyl-1,1’,2’,5-tetrahydro-2-methyl-5’-nitro-2’,5-dioxospiro[4H-indeno[1,2-b]pyridine-4,3’-
[3H]indole]-3-carboxylate (4y). Yield 85%. Orange powder. M.p. > 3008. IR (KBr): 3169, 1695, 1637,
1
1611. H-NMR: 1.28 (t, J ¼ 6.9, Me); 2.50 (s, Me); 3.33 (s, MeO); 3.82 – 3.84 (m, CH2N); 7.18 – 8.20 (m,
7 H); 10.43 (s, NH). 13C-NMR: 12.6; 20.0; 35.2; 49.5; 51.4; 103.9; 105.8; 108.1; 119.0; 120.5; 121.3; 126.1;
131.2; 132.6; 133.2; 134.1; 135.8; 137.2; 142.8; 149.3; 154.5; 166.3; 178.6; 189.7. EI-MS: 445 (Mþ). Anal.
calc. for C24H19N3O6 (445.42): C 64.72, H 4.30, N 9.43, found: C 64.79, H 4.38, N 9.47.
Ethyl 1’-Ethyl-1,1’,2’,5-tetrahydro-2-methyl-5’-nitro-2’,5-dioxospiro[4H-indeno[1,2-b]pyridine-4,3’-
[3H]indole]-3-carboxylate (4z). Yield 88%. Orange powder. M.p. > 3008. IR (KBr): 3164, 1716, 1695,
1654. 1H-NMR: 0.78 (t, J ¼ 6.6, Me); 1.22 (t, J ¼ 6.3, Me); 2.55 (s, Me); 3.72 – 3.92 (m, 2 CH2); 7.17 – 8.22
(m, 7 H); 10.63 (s, NH). 13C-NMR: 12.5; 13.9; 19.9; 33.7; 49.5; 60.1; 103.7; 105.9; 108.1; 119.0; 120.5;
121.3; 126.0; 131.2; 132.6; 133.2; 135.8; 137.3; 142.8; 149.4; 149.5; 154.4; 165.6; 178.6; 189.7. EI-MS: 459
(Mþ). Anal. calc. for C25H21N3O6 (459.45): C 65.35, H 4.61, N 9.15; found: C 65.28, H 4.58, N 9.04.
Methyl 1’,5’-Dihydro-2’-methyl-2,5’-dioxospiro[acenaphthylene-1(2H),4’-[4H-indeno[1,2-b]pyri-
dine]-3’-carboxylate (9a). Yield 79%. Red powder. M.p. > 3008. IR (KBr): 3226, 1690, 1643.
1H-NMR: 2.97 (s, Me); 3.37 (s, MeO); 7.03 – 8.20 (m, 10 H); 10.48 (s, NH). 13C-NMR: 19.6; 50.9; 54.4;
106.7; 108.5; 120.1; 120.5; 120.9; 121.0; 124.7; 128.7; 129.1; 129.3; 129.8; 130.9; 132.5; 133.1; 134.1; 136.0;
140.6; 145.4; 147.3; 154.1; 166.7; 189.9; 205.3. EI-MS: 407 (Mþ). Anal. calc. for C26H17NO4 (407.42): C
76.65, H 4.21, N 3.44; found: C 76.71, H 4.28, N 3.37.
Ethyl 1’,5’-Dihydro-2’-methyl-2,5’-dioxospiro[acenaphthylene-1(2H),4’-[4H-indeno[1,2-b]pyridine]-
3’-carboxylate (9b). Yield 80%. Red powder. M.p. > 3008. IR (KBr): 3221, 1701, 1680, 1638. 1H-NMR:
0.11 (t, J ¼ 6.9, Me); 2.49 (s, Me); 3.33 – 3.36 (m, CH2); 7.28 – 8.19 (m, 10 H); 10.52 (s, NH). 13C-NMR:
12.8; 19.5; 54.4; 59.6; 106.3; 108.6; 120.1; 120.5; 120.9; 121.2; 124.6; 128.7; 129.2; 129.5; 129.9; 131.0; 132.5;
133.2; 134.2; 136.0; 140.9; 145.5; 147.5; 154.0; 166.0; 190.0; 205.4. EI-MS: 421 (Mþ). Anal. calc. for
C27H19NO4 (421.44): C 76.95, H 4.54, N 3.32, found: C 76.83, H 4.47, N 3.27.
3’-Acetyl-2’-methylspiro[acenaphthylene-1(2H),4’-[4H-indeno[1,2-b]pyridine]-2,5’(1’H)-dione (9c).
Yield 75%. Red powder. M.p. > 3008. IR (KBr): 3179, 1716, 1643, 1622. 1H-NMR: 2.11 (s, Me); 2.52 (s,
Me); 7.03 – 8.15 (m, 10 H); 10.43 (s, NH). 13C-NMR: 20.3; 32.1; 54.9; 108.9; 119.4; 120.1; 120.7; 120.9;
123.4; 124.5; 128.7; 129.0; 129.7; 130.4; 130.9; 132.4; 133.1; 134.8; 136.0; 140.3; 145.7; 145.9; 154.0; 189.8;
197.1; 204.5. EI-MS: 391 (Mþ). Anal. calc. for C26H17NO3 (391.42): C 79.78, H 4.38, N 3.58; found: C
79.70, H 4.34, N 3.63.
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Received February 1, 2011