September 2010
A Clean and One-Pot Synthesis of Spiroindoline-Pyranopyrazoles
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Table 2
MIC (lg/mL) values of products 5 and 9.
Products
Standard
Tetracycline Gentamicin
5a 5b 5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
9
Bacillus subtilis
Bacillus pumilus
16
6
8
4
2
6
2
4
2
4
4
4
2
2
4
2
2
2
2
2
4
<2
<2
4
*
<2
8
32 16
16
2
32
64
16
2
24
4
8
32 16 32 32
16
4
8
*
*
*
*
*
*
4
*
8
8
16
2
4
4
16
2
Micrococcus luteus
Staphylococcus aureus
Staphylococcus epidermidis
Sterptococcus mutans
Escherichia coli
2
8
2
32
8
16
2
8
*
*
6
4
2
4
64
*
4
16
8
4
4
8
6
2
8
<2 128
<2
16
2
64
4
4
32
32
4
2
16
*
<2
2
*
6
4
2
4
64
4
8
4
32
4
2
2
4
4
8
2
Enterococcus faecalis
Pseudomonas aeruginosa
6
8
16
2
4
2
4
4
2
8
*
<2 <2 <2
4
8
* Not active.
[6] Da-Silva, J. F. M.; Garden, S. J.; Pinto, A. C. J Braz Chem
Soc 2001, 12, 273.
MHz, DMSO-d6): dH 0.50 (3H, t, 3JHH ¼ 7.2 Hz, CH3),
0.93–1.03 (2H, m, CH2), 1.66–1.82 (2H, m, CH2), 3.18 (3H,
s, CH3), 7.04–7.37 (4H, m, H-Ar), 7.26 (2H, s, NH2), 12.31
(1H, s, NH). 13C NMR (DMSO-d6): dc ¼ 13.8, 21.4, 26.3,
26.7, 47.4, 55.2, 95.3, 109.1, 119.0, 123.7, 124.7, 129.5, 132.6,
139.5, 143.3, 155.4, 162.9, 177.0. Anal. Calcd. for
C18H17N5O2: C, 64.47; H, 5.11; N, 20.88%. Found: C, 64.43;
H, 5.16; N, 20.94%.
[7] Abdel-Rahman, A. H.; Keshk, E. M.; Hanna, M. A.; El-
Bady, Sh. M. Bioorg Med Chem 2006, 12, 2483.
[8] Kang, T.-H.; Matsumoto, K.; Murakami, Y.; Takayama, H.;
Kitajima, M.; Aimi, N.; Watanabe, H. Eur J Pharmacol 2002, 444, 39.
[9] Ma, J.; Hecht, S. M. Chem Commun 2004, 1190.
[10] Khafagy, M. M.; El-Wahas, A. H. F. A.; Eid, F. A.; El-
Agrody, A. M. Farmaco 2002, 57, 715.
4-Methyl-1H-pyrrol-2-ol (6). White powder; m.p. 219–
222ꢀC. IR (KBr) (mmax/cmꢁ1): 3314, 3324, 2199, 1687. MS
[11] Zhu, S.-L.; Jia, S.-J.; Zhang, Y. Tetrahedron 2007, 63,
9365.
1
(EI, 70 eV) m/z: 98 (Mþ). H NMR (300 MHz, DMSO-d6): dH
2.35 (3H, s, CH3), 5.81 (1H, s, CH),12.86 (1H, s, NH).
[12] Kumar, R. S.; Perumal, S. Tetrahedron Lett 2007, 48, 7164.
[13] Redkin, R. Gr.; Shemchuk, L. A.; Chernykh, V. P.; Shish-
kin, O. V.; Shishkina, S. V. Tetrahedron 2007, 63, 11444.
[14] Shanthi, G.; Subbulakshmi, G.; Perumal, P. T. Tetrahedron
2007, 63, 2057.
2-(2-Oxoindolin-3-ylidene)malononitrile
(7). Brick-red
powder; m.p. 215–217ꢀC. IR (KBr) (mmax/cmꢁ1): 3236, 3016,
2232, 1611. MS (EI, 70 eV) m/z: 3195 (Mþ). 1H NMR (300
MHz, DMSO-d6): dH 6.91–7.86 (4H, m, H-Ar), 11.20 (1H, s,
NH).
[15] Al-Haiza, M. A.; Mostafa, M. S.; El-Kady, M. Y. Mole-
cules 2003, 8, 275.
60-Amino-30-methyl-2-oxo-2H,20H-spiro[acenaphthylene-
1,40-pyrano[2,3-c]pyrazole]-50-carbonitrile (9). Brown pow-
der (87%); m.p. 246ꢀC (dec). IR (KBr) (mmax/cmꢁ1): 3414,
3320, 2187, 1714. MS (EI, 70 eV) m/z: 328 (Mþ). 1H NMR
(300 MHz, DMSO-d6): dH 1.05 (3H, s, CH3), 7.31 (2H, s,
NH2), 7.45–8.40 (6H, m, H-Ar), 12.26 (1H, s, NH). 13C NMR
(DMSO-d6): dc ¼ 9.5, 52.1, 56.2, 96.7, 119.3, 121.7, 123.0,
125.4, 129.4, 129.9, 130.4, 131.0, 133.1, 135.1, 141.4, 141.5,
155.7, 162.9, 204.3. Anal. Calcd. for C19H12N4O2: C, 69.51;
H, 3.68; N, 17.06.%. Found: C, 69.57; H, 3.64; N, 17.11%.
[16] Kemnitzer, W.; Drewe, J.; Jiang, S.; Zhang, H.; Wang, Y.;
Zho, J.; Jia, S.; Herich, J.; Labreque, D.; Storer, R.; Meerovitch, K.;
Bouffard, D.; Rej, R.; Denis, R.; Blais, C.; Lamothe, S.; Attardo, G.;
Gourdeau, H.; Tseng, B.; Kasibhatla, S.; Cai, S. X. J Med Chem 2004,
47, 6299.
[17] Joshi, K. C.; Jain, R.; Sharma, K. J Indian Chem Soc 1988,
65, 202.
[18] Joshi, K. C.; Jain, R.; Arora, S. J Indian Chem Soc 1988,
65, 277.
[19] Higashiyama, K.; Otomasu, H. Chem Pharm Bull 1988, 28,
648.
[20] El-Tamany, E. S.; El-Shahed, F. A.; Mohamed, B. H.
J Serb Chem Soc 1999, 64, 553.
Acknowledgments. The authors gratefully acknowledge finan-
cial support from the Research Council of Shahid Beheshti
University.
[21] Ismail, Z. H.; Aly, G. M.; El-Degwi, M. S.; Heiba, H. I.;
Ghorab, M. M. Egyp J Biotechnol 2003, 13, 73.
[22] Zaki, M. E. A.; Soliman, H. A.; Hiekal, O. A.; Rashad, A.
E. Z Naturforsch C 2006, 61, 1.
[23] Bazgir, A.; Mohammadi Khanaposhtani, M.; Abolhasani
Soorki, A. Bioorg Med Chem Lett 2008, 18, 5800.
[24] Bazgir, A.; Seyyedhamzeh, M.; Yasaei, Z.; Mirzaei, P. Tet-
rahedron Lett 2007, 48, 8790.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet