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DOI: 10.1055/s-0030-1258506
Synthesis of Novel Spiro[dihydropyridine-oxindole] Compounds in Water
Publication History
Publication Date:
16 July 2010 (online)
Abstract
An efficient one-pot synthesis of the biologically important spiro[dihydropyridine-oxindole] scaffold was accomplished simply by the reaction of isatin, 2H-indene-1,3-dione and naphthalen-2-amine in aqueous medium. The scope of this reaction was successfully extended by employing two other reactive ketones (acenaphthylene-1,2-dione and ninhydrin) in place of isatin to access the synthesis of corresponding spirocyclic derivatives.
Key words
spirooxindole - isatin - dihydropyridine - acenaphthylene-1,2-dione - ninhydrin
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References and Notes
General Procedure
for the Synthesis of Spiro{1
H
-indeno[1,2-
b
]benzo[
f
]quinolin-13,3′-indoline}-7,13-dihydro-12,2′-dione
Derivatives 4a-e
To a stirred mixture of
2H-indene-1,3-dione (1,
0.146 g, 1 mmol), naphthalen-2-amine 2 (0.143
g, 1 mmol), and an isatin derivatives 3a-e (1 mmol) in a solution of H2O-EtOH [6
mL, 5:1 (v/v)], was added a catalytic amount of
PTSA (monohydrate, 0.1 g). The mixture was stirred at 60 ˚C
(oil bath) for about 15 min (as monitored by TLC). After completion,
the reaction mixture was filtered and the obtained precipitate washed
with hot EtOH (95.5%).
Spiro{1
H
-indeno[1,2-
b
]benzo[
f
]quinolin-13,3′-indoline}-7,13-dihydro-12,2′-dione
(4a)
Red powder (0.340 g, 85%); mp 298-300 ˚C.
IR (KBr): 3470, 3210, 3050, 1688, 1672, 1618 cm-¹. ¹H
NMR (400.13 MHz, DMSO-d
6): δ = 6.67
(1 H, d, J = 8.4
Hz, 1-H), 6.86 (1 H, t, J = 7.2Hz,
4′-H), 6.96 (2 H, t, J = 8.0
Hz, 5′-H and 6′-H), 7.21 (1 H, t, J = 7.6 Hz,
7′-H), 7.26 (1 H, d, J = 6.8
Hz), 7.41 (1 H, t, J = 7.2
Hz), 7.54 (1 H, d, J = 8.8
Hz), 7.55 (1 H, t, J = 8.0
Hz), 7.62 (1 H, t, J = 7.2
Hz), 7.73 (1 H, t, J = 6.8 Hz),
7.88 (1 H, d, J = 8.0
Hz), 8.18 (1 H, d, J = 7.2
Hz), 8.76 (1 H, d, J = 8.4
Hz), 10.36 (1 H, s, NH), 10.65 (1 H, s, NH). ¹³C
NMR (100.6 MHz, DMSO-d
6): δ = 51.3
(Cspiro), 104.0 (C-12a), 110.0 (C-11a), 120.5, 120.6,
121.1, 122.3, 122.7, 123.9, 125.1, 125.2, 125.4, 127.0, 127.3, 128.7,
128.8, 130.9, 131.8, 132.0, 133.3, 134.2, 136.8, 138.4, 141.9 (C-6a),
156.5 (C-7a), 180.0 (amidic C=O), 189.6 (C=O).
MS (EI, 70 eV): m/z (%) = 400(56) [M+],
384 (14), 371 (100), 355 (95). Anal. Calcd for C27H16N2O2:
C, 80.99; H, 4.03; N, 7.00. Found: C, 81.03; H, 4.21; N, 6.89.
Spiro{1
H
-indeno[1,2-
b
]benzo[
f
]quinolin-13,3′-indoline}-7,13-dihydro-5′-nitro-12,2′-dione
(4b)
Red powder (0.360, 81%); mp 304 ˚C
(decomp.). IR (KBr): 3470, 3240, 1706, 1620, 1527, 1330 cm-¹. ¹H
NMR (400.13 MHz, DMSO-d
6): δ = 6.69
(1 H, d, J = 8.8
Hz, 1-H), 7.21 (1 H, d, J = 8.8
Hz, 7′-H), 7.28 (1 H, d, J = 7.2
Hz), 7.43 (1 H, t, J = 7.2
Hz), 7.57 (1 H, t, J = 7.2
Hz), 7.58 (1 H, d, J = 8.8 Hz),
7.65 (1 H, t, J = 7.6
Hz), 7.76 (1 H, t, J = 7.2
Hz), 7.86 (1 H, d, J = 2.0
Hz, 4′-H), 7.91 (1 H, d, J = 8.0
Hz), 8.22 (1 H, dd, J = 8.8,
2.4 Hz), 8.23 (1 H, d, J = 8.4
Hz), 8.82 (1 H, d, J = 8.4
Hz), 10.52 (1 H, s, NH), 11.42 (1 H, s, NH). ¹³C NMR
(100.6 MHz, DMSO-d
6): δ = 51.4
(Cspiro), 102.7 (C-12a), 110.4 (C-11a), 119.0, 120.7,
120.8, 121.5, 122.5, 124.0, 125.1, 125.7, 126.3, 127.2, 127.6, 128.8,
131.1, 132.1, 132.3, 133.6, 134.2, 136.7, 138.8, 143.2, 148.6 (C-6a),
157.0 (C-7a), 180.4 (amidic C=O), 189.6 (C=O).
MS (EI, 70 eV): m/z (%) = 445
(48) [M+], 443 (100) [M+ - 2], 417
(60) [M+ - C=O],
400(89), 399 (75) [417 - H2O],
369 (76). Anal. Calcd for C27H15N3O4:
C, 72.80; H, 3.39; N, 9.43. Found: C, 72.76; H, 3.42; N, 9.37.
Spiro[1H-indeno[1,2-b]benzo[f]quinolin-13,3-indoline]-7,13-dihydro-5′-methoxy-12,2′-dione
(4c)
Orange powder (0.335 g, 78%); mp 306-308 ˚C.
IR (KBr): 3237, 1703, 1684, 1532, 1187, 1175 cm-¹. ¹H
NMR (400.13 MHz, DMSO-d
6): δ = 3.56
(3 H, s, OCH3), 6.56 (1 H, d, J = 2.4
Hz, 4′-H), 6.67 (1 H, d, J = 8.8
Hz, 1-H), 6.79 (1 H, dd, J = 8.4,
2.0 Hz, 6′-H), 6.89 (1 H, d, J = 8.8
Hz, 7′-H), 7.26 (1 H, d, J = 6.8
Hz), 7.41 (1 H, t, J = 7.2
Hz), 7.54 (1 H, d, J = 8.0
Hz), 7.55 (1 H, t, J = 6.4
Hz), 7.61 (1 H, t, J = 7.6 Hz),
7.72 (1 H, t, J = 7.2
Hz), 7.88 (1 H, d, J = 8.0
Hz), 8.17 (1 H, d, J = 7.2
Hz), 8.76 (1 H, d, J = 8.4
Hz), 10.35 (1 H, s, NH), 10.48 (1 H, s, NH). ¹³C
NMR (100.6 MHz, DMSO-d
6): δ = 51.8
(Cspiro), 55.8 (OCH3), 102.8 (C-12a), 110.4
(C-11a), 111.7, 113.7, 120.5, 120.6, 121.1, 122.4, 123.9, 125.2, 125.4,
127.0, 127.2, 128.7, 130.9, 131.8, 132.0, 133.4, 134.3, 135.3, 136.8,
139.6, 155.8 (C-6a), 156.6 (C-7a), 179.9 (amidic C=O),
189.6 (C=O). MS (EI, 70 eV): m/z (%) = 430 (98) [M+],
402 (100) [M+ - C=O],
385 (88). Anal. Calcd for C28H18N2O3:
C, 78.13; H, 4.21; N, 6.51. Found: C, 78.22; H, 4.33; N, 6.46.
Spiro{1
H
-indeno[1,2-
b
]benzo[
f
]quinolin-13,3′-indoline}-7,13-dihydro-1′-benzyl-12,2′-dione
(4e)
Orange powder (0.387 g, 79%); mp 310 ˚C
(decomp.). IR (KBr): 3235, 1686, 1622, 1604, 1526, 1362 cm-¹. ¹H
NMR (400.13 MHz, DMSO-d
6): δ = 5.00
(1 H, d, J = 16.0
Hz), 5.13 (1 H, d, J = 16.0
Hz), 6.58 (1 H, d, J = 8.8
Hz, 1-H), 6.91-6.96 (2 H, m), 7.05 (1 H, d, J = 7.2 Hz,
7′-H), 7.21 (1 H, t, J = 7.6
Hz), 7.27-7.45 (6 H, m), 7.51-7.59 (3 H, m), 7.64
(1 H, t, J = 7.6
Hz), 7.75 (1 H, t, J = 7.6
Hz), 7.89 (1 H, d, J = 8.4
Hz), 8.22 (1 H, d, J = 7.2
Hz), 8.79 (1 H, d, J = 8.4 Hz),
10.47 (1 H, s, NH). MS (EI, 70 eV): m/z (%) = 490
(34) [M+], 461 (4) [M+ - HCO],
399 (100) [M+ - benzyl],
371 (86) [399 - C=O]. Anal.
Calcd for C34H22N2O2:
C, 83.25; H, 4.52; N, 5.71. Found: C, 83.12; H, 4.59; N, 5.58.
Due
to the very low solubility of compounds 4d and 4e we were unable to obtain their ¹³C
NMR spectra.
Spiro{1
H
-indeno[1,2-
b
]benzo[
f
]quinolin-13,1′(2′
H
)-acenaphthylene}-7,13-dihydro-12,2′-dione
(9)
Brick red powder (0.352 g, 81%); mp 284-286 ˚C.
IR (KBr): 3295, 1702, 1684, 1620, 1586, 1525 cm-¹. ¹H
NMR (400.13 MHz, DMSO-d
6): δ = 6.27
(1 H, d, J = 8.8
Hz, 1-H), 7.17 (1 H, d, J = 6.8
Hz), 7.34 (1 H, d, J = 6.8
Hz), 7.38-7.40 (2 H, m), 7.57 (1 H, t, J = 7.2
Hz), 7.62 (1 H, t, J = 8.6
Hz), 7.64 (1 H, t, J = 8.4
Hz), 7.74-7.91 (3 H, m), 8.02 (1 H, d, J = 8.4
Hz), 8.12 (1 H, d, J = 6.8
Hz), 8.22 (1 H, d, J = 7.6 Hz),
8.41 (1 H, d, J = 8.4
Hz), 8.82 (1 H, d, J = 8.8
Hz), 10.45 (1 H, s, NH). ¹³C NMR (100.6
MHz, DMSO-d
6): δ = 57.2
(Cspiro), 105.3 (C-12a), 120.6 (C-11a), 121.2, 121.9, 122.4,
123.18, 123.22, 124.0, 125.1, 125.2, 125.6, 127.1, 127.3, 128.7,
129.4, 129.9, 130.4, 131.0, 132.0, 132.1, 132.5, 132.7, 133.3, 134.1,
136.7, 136.8, 141.9 (C-6a), 158.7 (C-7a), 189.9 (C=O),
209.8 (C=O). MS (EI, 70 eV): m/z (%) = 435
(82) [M+], 407 (78) [M+ - C=O],
406 (100) [M+ - HC=O].
Anal. Calcd for C31H17NO2: C, 85.50;
H, 3.93; N, 3.22. Found: C, 85.61; H, 4.11; N, 3.14.
Spiro{1
H
-indeno[1,2-
b
]benzo[
f
]quinolin-13,2′-indene}-7,13-dihydro-12,1′,3′-trione
(10)
Red powder (0.326 g, 79%); mp 286-288 ˚C.
IR (KBr): 3303, 1740, 1697, 1624, 1587, 1524, 1250 cm-¹. ¹H
NMR (400.13 MHz, DMSO-d
6): δ = 6.63
(1 H, d, J = 8.4
Hz, 1-H), 7.28 (1 H, d, J = 7.2
Hz), 7.45 (1 H, t, J = 7.2
Hz), 7.58 (1 H, t, J = 8.4
Hz), 7.59 (1 H, t, J = 8.4
Hz), 7.66 (1 H, t, J = 7.6 Hz),
7.76 (1 H, t, J = 7.2
Hz), 7.93 (1 H, d, J = 8.4
Hz), 8.15-8.19 (4 H, m), 8.20 (1 H, d, J = 7.2
Hz), 8.78 (1 H, d, J = 8.8 Hz),
10.58 (1 H, s, NH). ¹³C NMR (100.6
MHz, DMSO-d
6): δ = 57.5
(Cspiro), 118.1 (C-12a), 120.9 (C-11a), 121.6, 122.4, 123.4,
124.0, 124.4 (2 CH), 124.6, 125.8, 127.5, 127.7, 128.9, 131.4, 132.3,
132.8, 133.5, 133.7, 136.5, 137.5 (2 CH), 142.8 (2 C), 157.9 (C-7a),
189.6 (C=O), 200.6 (2 C=O). MS (EI, 70 eV): m/z (%) = 413
(87) [M+], 397 (60), 385 (65) [M+ - C=O],
384 (100) [M+ - HC=O],
369 (54), 356 (45) [384 - C=O].
Anal. Calcd for C28H15NO3: C, 81.35;
H, 3.66; N, 3.39. Found: C, 81.39; H, 3.73; N, 3.32.