PAPER
One-Pot Synthesis of Spirooxindole Derivatives in Water
1383
MS: m/z (%) = 371 (1) [M+], 368 (12), 311 (16), 294 (18), 192 (38),
164 (100), 134 (50), 106 (66), 90 (98), 75 (99), 63 (99), 51 (95).
Anal. Calcd for C16H14N64O5 (370.32): C, 51.89; H, 3.81; N, 22.69.
Found: C, 51.92; H, 3.24; N, 22.55.
Anal. Calcd for C16H13N5O6 (371.31): C, 51.76; H, 3.53; N, 18.86.
Found: C, 51.95; H, 3.95; N, 18.91.
7′-Amino-1-benzyl-5-bromo-1′,3′-dimethyl-6′-nitro-1′H-spi-
ro[indoline-3,5′-pyrido[2,3-d]pyrimidine]-2,2′,4′(3′H,8′H)-tri-
one (3g)
2′-Amino-5-bromo-1-methyl-3′-nitro-7′,8′-dihydro–1′H-spi-
ro[indoline-3,4′-quinoline]-2,5′(6′H)-dione (3d)
Yield: 0.31 g (75%); cream powder; mp 280–282 °C (dec.).
Yield: 0.43 g (80%); cream powder; mp 283–285 °C (dec.).
IR (KBr): 3431 (2 NH and NH2), 1714 (CH3NCONCH3), 1687
(CONH), 1631 (CON), 1380 (NO2) cm–1.
1H NMR (500.13 MHz, DMSO-d6): δ = 3.03 (s, 3 H, NCH3), 3.42
(s, 3 H, CONCH3CO), 4.80 (br s, 1 H, CH2Ph), 5.00 (br s, 1 H,
CH2Ph), 6.59 (s, 1 H, NH2), 6.96–7.50 (m, 8 H, Ar), 9.80 (br s, 1 H,
NH2), 10.01 (s, 1 H, NH).
13C NMR (125.75 MHz, DMSO-d6): δ = 27.8 (CONCH3), 29.7
(CONCH3CO), 41.9 (CH2Ph), 44.2 (Cspiro), 88.7 (COCCspiro), 106.5
(CNO2), 109.8 (CH of Ar), 113.6 (Cipso-Br), 125.8 (CH of Ar), 127.1
(Cpara of Ph), 127.3 (Cortho of Ph), 128.3 (Cmeta of Ph), 130.8 (CH of
Ar), 132.4 (Cipso of Ph), 136.3 (Cipso-Cspiro), 144.6 (Cipso-NH), 149.3
(NHCNCH3), 150.7 (NH2CNH), 157.1 (CH3NCONCH3), 158.9
(CONCH3), 175.0 (CONH).
IR (KBr): 3409, 3295, 3220 and 3057 (2 NH and NH2), 1697 (CO),
1631 (CON), 1372 (NO2) cm–1.
1H NMR (500.13 MHz, DMSO-d6): δ = 1.74–1.92 (m, 2 H,
CH2CH2CH2), 2.45–2.64 (m, 2 H, CH2CNH), 3.04–3.16 (m, 2 H,
3
CH2CO), 3.32 (s, 3 H, NCH3), 6.80 (d, JH–H = 8.0 Hz, 1 H, Ar),
7.13 (s, 1 H, Ar), 7.30 (d, 3JH–H = 7.8 Hz, 1 H, Ar), 7.60 (br s, 1 H,
NH2), 9.46 (br s, 1 H, NH2), 9.86 (s, 1 H, NH).
13C NMR (125.75 MHz, DMSO-d6): δ = 20.2 (CH2CH2CH2), 26.3
(CH2CNH), 26.9 (CH2CO), 36.9 (NCH3), 50.6 (Cspiro), 108.4 (CH of
Ar), 108.6 (CNO2), 111.6 (COCCspiro), 112.8 (Cipso-Br), 124.6 (CH
of Ar), 130.1 (CH of Ar), 134.0 (Cipso-Cspiro), 145.2 (Cipso-NH),
150.0 (NHCCH2), 151.2 (NH2CNH), 176.3 (CONH), 192.9 (CO).
MS: m/z (%) = 539 (1) [M+], 385 (3), 156 (7), 91 (100), 65 (13).
MS: m/z (%) = 419 (1) [M+], 393 (2), 368 (5), 313 (5), 239 (6), 111
Anal. Calcd for C23H19BrN6O5 (539.34): C, 51.32; H, 3.55; N,
15.58. Found: C, 51.24; H, 3.45; N, 15.64.
(8), 83 (78), 55 (100).
Anal. Calcd for C17H15BrN4O4 (419.23): C, 48.70; H, 3.61; N,
13.36. Found: C, 48.83; H, 3.57; N, 13.28.
References
2′-Amino-7′,7′-dimethyl-3′-nitro-7′,8′-dihydro-1′H-spiro[in-
doline-3,4′-quinoline]-2,5′(6′H)-dione (3e)
Yield: 0.30 g (85%); cream powder; mp 244–246 °C (dec.).
(1) Ahadi, S.; Ghahremanzadeh, R.; Mirzaei, P.; Bazgir, A.
Tetrahedron 2009, 65, 9316.
IR (KBr): 3341, 3256, 3205 and 3153 (2 NH and NH2), 1711 (CO),
1670 (CON), 1352 (NO2) cm–1.
(2) Rajabi Khorrami, A.; Faraji, F.; Bazgir, A. Ultrason.
Sonochem. 2011, 18, 635.
1H NMR (500.13 MHz, DMSO-d6): δ = 0.93 (s, 3 H, CH3), 1.00 (s,
(3) Rajab Khorrami, A.; Faraji, F.; Bazgir, A. Ultrason.
Sonochem. 2010, 17, 587.
(4) Poornachandran, M.; Raghunathan, R. Tetrahedron 2006,
62, 11274.
3 H, CH3), 2.10 (AB system, 2JH–H = 15.8 Hz, 2 H, CH2CNH), 2.57
2
(AB system, JH–H = 17.5 Hz, 2 H, CH2CO), 6.71–7.08 (m, 4 H,
Ar), 9.56 (br s, 3 H, NH2 and NH), 10.42 (s, 1 H, NH).
(5) For early surveys of oxindole alkaloids, see: (a) Cordell, G.
A. An Introduction to Alkaloids, In A Biogenetic Approach;
Wiley-Interscience: New York, 1981. (b) Bindra, J. S. The
Alkaloids-Chemistry and Physiology Oxindole Alkaloids,
Vol. 14; Manske, R. H. F., Ed.; Academic: New York, 1973,
83.
(6) For reviews of gelsemium alkaloids, see: (a) Liu, Z. J.; Lu,
R. R. The Alkaloids 1988, 33, 83. (b) Saxton, J. E. The
Alkaloids 1965, 8, 93.
13C NMR (125.75 MHz, DMSO-d6): δ = 26.6 (CH3), 27.6 (CH3),
31.5 (CH2CNH), 39.8 (Cq), 50.4 (CH2CO), 54.9 (Cspiro), 107.6
(CNO2), 108.5 (CH of Ar), 113.2 (COCCspiro), 120.8 (CH of Ar),
122.2 (CH of Ar), 127.9 (CH of Ar), 131.1 (Cipso-Cspiro), 144.5
(Cipso-NH), 157.8 (NHCCH2), 161.8 (NH2CNH), 176.7 (CONH),
194.1 (CO).
MS: m/z (%) = 354 (2) [M+], 308 (31), 294 (100), 266 (41), 226
(39), 141 (25), 115 (32), 83 (39).
(7) (a) Chang, M. Y.; Pai, C. L.; Kung, Y. H. Tetrahedron Lett.
2005, 46, 8463. (b) Baran, S. P.; Richter, R. M. J. Am. Chem.
Soc. 2005, 127, 15394. (c) Hilton, S. T.; Ho, T. C.;
Pljevaljcic, G.; Jones, K. Org. Lett. 2000, 2, 2639. (d) Cui,
C. B.; Kakeya, H.; Okada, G.; Onose, R.; Osada, H.
J. Antibiot. 1996, 49, 527.
Anal. Calcd for C18H18N4O4 (354.36): C, 61.01; H, 5.12; N, 15.81.
Found: C, 59.83; H, 5.13; N, 15.78.
7′-Amino-1′,3′-dimethyl-6′-nitro-1′H-spiro[indoline-3,5′-pyri-
do[2,3-d]pyrimidine]-2,2′,4′(3′H,8′H)-trione (3f)
Yield: 0.30 g (80%); cream powder; mp 240–242 °C (dec.).
IR (KBr): 3349 and 3300 (2 NH and NH2), 1698 (CONH), 1718
(CH3NCONCH3), 1685 (CONH), 1651 (CON), 1383 (NO2) cm–1.
1H NMR (500.13 MHz, DMSO-d6): δ = 3.00 (s, 3 H, NCH3), 3.41
(s, 3 H, CONCH3CO), 6.74–7.09 (m, 4 H, Ar), 9.78 (br s, 3 H, NH2
and NH), 10.49 (s, 1 H, NH).
13C NMR (125.75 MHz, DMSO-d6): δ = 27.7 (CONCH3), 29.7
(CONCH3CO), 48.4 (Cspiro), 89.4 (COCCspiro), 107.3 (CNO2), 108.5
(CH of Ar), 120.8 (CH of Ar), 122.9 (CH of Ar), 128.1 (CH of Ar),
130.6 (Cipso-Cspiro), 144.5 (Cipso-NH), 149.4 (NHCNCH3), 150.4
(NH2CNH), 157.0 (CH3NCONCH3), 158.7 (CONCH3), 176.3
(CONH).
MS: m/z (%) = 370 (1) [M+], 355 (11), 324 (20), 310 (19), 294 (44),
215 (52), 169 (37), 156 (80), 141 (100), 114 (80), 91 (29), 71 (37),
56 (37).
(8) (a) Jossang, A.; Jossang, P.; Hadi, H. A.; Sevenet, T.; Bodo,
B. J. Org. Chem. 1991, 56, 6527. (b) Ghosal, S.; Banerjee, P.
K. Indian J. Chem. 1971, 9, 289. (c) Jones, K.; Wilkinson, J.
J. Chem. Soc., Chem. Commun. 1992, 1767. (d) Bascop, S.
I.; Sapi, J.; Laronze, J. Y.; Levy, J. Heterocycles 1994, 38,
725. (e) Pellegrini, C.; Strassler, C.; Weber, M.; Borschberg,
H. J. Tetrahedron: Asymmetry 1994, 5, 1979. (f) Palmisano,
G.; Annunziata, R.; Papeo, G.; Sisti, M. Tetrahedron:
Asymmetry 1996, 7, 1.
(9) (a) Nakamichi, N.; Kawashita, Y.; Hayashi, M. Org. Lett.
2002, 4, 3955. (b) Nakamichi, N.; Kawashita, Y.; Hayashi,
M. Synthesis 2004, 1015.
(10) (a) Buhler, F. R.; Kiowski, W. J. Hypertens. 1987, S3, 5.
(b) Reid, J. L.; Meredith, P. A.; Pasanisi, F. J. Cardiovasc.
Pharmacol. 1985, S18, 7.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 1380–1384