PDF herunterladen
Synlett 2012(3): 428-432  
DOI: 10.1055/s-0031-1290322
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A Unique Approach to Catalyst-Free, One-Pot Synthesis of Spirooxindole-Pyrazolines

Abdolali Alizadeh*, Nasrin Zohreh
Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran
Fax: +98(21)88006544; e-Mail: abdol_alizad@yahoo.com; e-Mail: aalizadeh@modares.ac.ir;
Weitere Informationen

Publikationsverlauf

Received 21 October 2011
Publikationsdatum:
25. Januar 2012 (online)

    Lizenzen und Reprints Alle Artikel dieser Rubrik

Abstract

A pseudo-five-component synthesis of spirooxindole-pyrazolines via a one-pot and catalyst-free reaction under mild conditions is reported. The 1,1-bishydrazino-2-nitroethylene intermediate generated in situ from the addition of aqueous hydrazine to 1,1-bis(methylthio)-2-nitroethylene is trapped by two equivalents of isatin derivatives to obtain the title compounds.

Key words

spirooxindole - isatin - spiropyrazole - pyrazoline - 1,1-bis(methylthio)-2-nitroethylene - one-pot reaction

    References and Notes

  • 1a Nicolaou KC. Vourloumis D. Winssinger N. Baran PS. Angew. Chem. Int. Ed.  2000,  39:  44 
    Google Scholar
  • 1b Nicolaou KC. Snyder SA. Proc. Natl. Acad. Sci. U.S.A.  2004,  101:  11929 
    Google Scholar
  • 1c Nicolaou KC. Edmonds DJ. Bulger PG. Angew. Chem. Int. Ed.  2006,  45:  7134 
    Google Scholar
  • 1d Li JWH. Vederas JC. Science  2009,  325:  161 
    Google Scholar
  • 1e Gaich T. Baran PS. J. Org. Chem.  2010,  75:  4657 
    Google Scholar
  • 2 Edmondson S. Danishefsky SJ. Sepp-Lorenzino L. Rosen N. J. Am. Chem. Soc.  1999,  121:  2147 
    Google Scholar
  • 3a Trost BM. Jiang C. Synthesis  2006,  369 
    Google Scholar
  • 3b Williams RM. Cox RJ. Acc. Chem. Res.  2003,  36:  127 
    Google Scholar
  • 3c Galliford CV. Scheidt KA. Angew. Chem. Int. Ed.  2007,  46:  8748 
    Google Scholar
  • 3d Marti C. Carreira EM. Eur. J. Org. Chem.  2003,  2209 
    Google Scholar
  • 3e Lin H. Danishefsky SJ. Angew. Chem. Int. Ed.  2003,  42:  36 
    Google Scholar
  • 4a Kornet MJ. Thio AP. J Med Chem.  1976,  19:  892 
    Google Scholar
  • 4b Rottmann M. McNamara C. Yeung BKS. Lee MCS. Zou B. Russell B. Seitz P. Plouffe DM. Dharia NV. Tan J. Cohen SB. Spencer KR. González-Páez GE. Lakshminarayana SB. Goh A. Suwanarusk R. Jegla T. Schmitt EK. Beck H.-P. Brun R. Nosten F. Renia L. Dartois V. Keller TH. Fidock DA. Winzeler EA. Diagana TT. Science  2010,  329:  1175 
    Google Scholar
  • 5 Dandia A. Singh R. Saha M. Shivpuri A. Pharmazie  2002,  57:  602 
    Google Scholar
  • 6 Mishra AD. J. Nepal Chem. Soc.  2009,  24:  49 
    Google Scholar
  • 7 Velikorodov AV. Poddubnyi OYu. Kuanchalieva AK. Krivosheev OO. Russ. J. Org. Chem.  2010,  46:  1826 
    Google Scholar
  • 8a Alizadeh A. Firuzyar T. Mikaeili A. Synthesis  2010,  3913 
    Google Scholar
  • 8b Alizadeh A. Mikaeili A. Firuzyar T. Helv. Chim. Acta  2011,  94:  1343 
    Google Scholar
  • 9a Zohreh N. Alizadeh A. Bijanzadeh HR. Zhu LG. J. Comb. Chem.  2010,  12:  497 
    Google Scholar
  • 9b Zohreh N. Alizadeh A. Tetrahedron  2009,  65:  2684 
    Google Scholar
  • 9c Alizadeh A. Zohreh N. Zhu LG. Tetrahedron  2009,  65:  268 
    Google Scholar
  • 9d Alizadeh A. Zohreh N. Helv. Chim. Acta  2010,  93:  1221 
    Google Scholar
  • 9e Alizadeh A. Zohreh N. Zhu LG. Oskueyan G. Synlett  2011,  2491 
    Google Scholar
  • 11a Jadidi K. Ghahremanzadeh R. Bazgir A. J. Comb. Chem.  2009,  11:  341 
    Google Scholar
  • 11b Ghahremanzadeh R. Sayyafi M. Ahadi S. Bazgir A. J. Comb. Chem.  2009,  11:  393 
    Google Scholar
  • 11c Imani Shakibaei G. Feiz A. Khavasi HR. Abolhasani Soorki A. Bazgir A. ACS Comb. Sci.  2011,  13:  96 
    Google Scholar
  • 11d Ghahremanzadeh R. Ahadi S. Imani Shakibaei G. Bazgir A. Tetrahedron Lett.  2010,  51:  499 
    Google Scholar
  • 11e Ahadi S. Ghahremanzadeh R. Mirzaei P. Bazgir A. Tetrahedron  2009,  65:  9316 
    Google Scholar
10

Synthesis of Compound 2
To a magnetically stirred 10 mL flask containing 1,1-bis(thiomethyl)-2-nitroethylene (0.17 g, 1 mmol) in EtOH (4 mL) was added NH2NH2˙H2O (80% aq, 0.12g, 2 mmol). After 5 h, isatin (0.30 g, 2 mmol) was added to the reaction mixture, and stirring was allowed to continue for 3 h. After the completion of the reaction, the precipitated product was filtered and washed with cold EtOH. Product 2a was obtained as an orange powder.
Analytical Data for Compounds 2
Compound 2a: yield 0.30 g (76%); mp >300 ˚C (dec.). IR (KBr): 3100-3500 (2 br bands, 5 NH), 1715 (2 NC=O), 1616 (C=N, C=C), 1558 and 1340 (NO2) cm-¹. ¹H NMR (500 MHz, DMSO-d 6): δ = 6.13 (2 H, s, 2 NH), 6.87-7.07 (4 H, m, 4 CH of Ar), 7.36 (3 H, br, 3 CH of Ar), 8.17 (1 H, br, CH of Ar), 10.79 (1 H, s, NH), 11.21 (1 H, s, NH), 13.37 (1 H, s, NH). ¹H NMR (500 MHz, DMSO-d 6-D2O): δ = 6.84 (1 H, d, ³ J HH = 7.6 Hz, CH of Ar), 6.88 (1 H, d, ³ J HH = 7.6 Hz, CH of Ar), 6.96 (1 H, t, ³ J HH = 8.1 Hz, CH of Ar), 7.02 (1 H, t, ³ J HH = 7.5 Hz, CH of Ar), 7.29-7.34 (3 H, m, 3 CH of Ar), 8.11 (1 H, d, ³ J HH = 7.4 Hz, CH of Ar). ¹³C NMR (125.7 MHz, DMSO-d 6): δ = 74.3 (Cspiro), 110.6 (CH), 111.2 (CH), 116.6 (C), 119.4 (C), 120.3 (CH), 122.0 (CH), 122.4 (CH), 129.1 (CH), 131.6 (CH), 133.8 (CH), 135.4 (C), 142.4 (C), 145.0 (C), 150.3 (C), 151.0 (C), 162.5 (C=O), 164.2 (C=O). MS: m/z (%) = 391 (4) [M+], 368 (10), 313 (7), 239 (13), 147 (30), 132 (25), 118 (55), 104 (49), 91 (37), 77 (78), 67 (30), 57 (100), 56 (85).
Compound 2b: yield 0.29 g (70%); orange powder; mp 280 ˚C (dec). IR (KBr): 3440 (br, 3 NH), 1715 (2 NC=O), 1613 (C=N, C=C), 1561 and 1360 (NO2) cm-¹. ¹H NMR (500 MHz, DMSO-d 6): δ = 3.21 (3 H, s, Me), 3.33 (3 H, s, Me), 6.15 (2 H, s, 2 NH), 7.06-7.15 (4 H, m, 4 CH of Ar), 7.38-7.49 (3 H, m, 3 CH of Ar), 8.20 (1 H, d, ³ J HH = 7.4 Hz, CH of Ar), 13.36 (1 H, s, NH). ¹³C NMR (125.7 MHz, DMSO-d 6): δ = 25.7 (Me), 26.0 (Me), 74.3 (Cspiro), 109.3 (CH), 110.0 (CH), 116.0 (C), 118.7 (C), 120.0 (CH), 122.6 (CH), 123.0 (CH), 128.8 (CH), 131.6 (CH), 133.8 (CH), 134.8 (C), 143.6 (C), 146.1 (C), 149.7 (C), 151.1 (C), 160.8 (C=O), 162.7 (C=O). MS: m/z (%) = 419 (9) [M+], 373 (10), 232 (12), 214 (13), 200(7), 187 (30), 186 (30), 185 (31), 173 (21), 160 (59), 146 (45),131 (100), 117 (95), 104 (63), 90 (86), 77 (55), 63 (17), 51 (22).
Compound 2c: yield 0.37 g (65%); orange powder; mp 238-240 ˚C. IR (KBr): 3447 and 3201 (br, 3 NH), 1722 (2 NC=O), 1610 (C=N, C=C), 1559 and 1353 (NO2) cm-¹. ¹H NMR (500 MHz, DMSO-d 6): δ = 4.97 (4 H, d, ³ J HH = 15.7 Hz, 2 CH2), 6.20 (2 H, s, 2 NH), 6.97-7.11 (6 H, m, 5 CH of Ar), 7.27-7.374 (12 H, m, 10 CH of Ar), 8.29 (1 H, d, ³ J HH = 6.9 Hz, CH of Ar), 13.42 (1 H, s, NH). ¹³C NMR (125.7 MHz, DMSO-d 6): δ = 42.6 (CH2), 42.8 (CH2), 74.3 (Cspiro), 109.9 (CH), 110.5 (CH), 116.1 (C), 118.9 (C), 119.5 (C), 120.2 (CH), 122.8 (CH), 123.1 (CH),127.2 (2 CH), 127.3 (2 CH), 127.5 (CH), 127.5 (CH), 128.7 (4 CH), 129.0 (CH), 131.5 (CH), 133.7 (CH), 134.7 (C), 135.6 (C), 136.0 (C), 145.08 (C), 149.54 (C),151. 51 (C), 160.81 (C=O), 163.0 (C=O). MS: m/z (%) = 368 (20), 353 (5), 339 (3), 313 (14), 299 (12), 285 (8), 255 (16), 236 (48), 222 (10), 208 (12), 194 (22), 152 (24), 125 (19), 111 (36), 97 (67), 83 (76), 69 (90), 57 (100).
Compound 2d: yield 0.38 g (65%); orange powder; mp 249 ˚C. IR (KBr): 3440 (br, 3 NH), 1722 (2 NC=O), 1607 (C=N and C=C), 1561 and 1352 (NO2) cm-¹. ¹H NMR (500 MHz, DMSO-d 6): δ = 2.25 (6 H, s, 2 Me), 4.93 (4 H, d, ³ J HH = 15.2 Hz, 2 CH2), 6.18 (2 H, s, 2 NH), 6.96-7.04 (4 H, m, 4 CH of Ar), 7.14 (2 H, d, ³ J HH = 5.8 Hz, 4 CH of Ar), 7.26 (2 H, d, ³ J HH = 6.5 Hz, 4 CH of Ar), 7.35-7.42 (4 H, m, 4 CH of Ar), 8.25 (1 H, d, ³ J HH = 6.4 Hz, CH of Ar), 13.41 (1 H, s, NH). ¹³C NMR (125.7 MHz, DMSO-d 6): δ = 20.6 (2 Me), 42.3 (CH2), 42.5 (CH2), 74.3 (Cspiro), 109.9 (CH), 110.6 (CH), 116.1 (C), 118.9 (C), 119.6 (C), 120.2 (CH), 122.7 (CH), 123.1 (CH),127.3 (2 CH), 127.3 (2 CH), 129.2 (4 CH), 131.4 (C), 131.5 (C), 132.2 (CH), 132.5 (CH), 133.7 (CH), 136.7 (C), 136.8 (C), 145.1 (C), 149.6 (C), 151.5 (C), 160.8 (C=O), 163.1 (C=O). MS: m/z (%) = 551 (5), 523 (7), 368 (26), 353 (8), 313 (11), 285 (6), 255 (14), 236 (45), 221 (11), 194 (13), 152 (17), 123 (21), 105 (72), 83 (65), 77 (81), 57 (100).
Compound 2e: yield 0.31 g (64%); mustard powder; up 300 ˚C. IR (KBr): 3000-3500 (2 br bands, 5 NH), 1732 (2 NC=O), 1618 (C=N, C=C), 1545 and 1339 (NO2) cm-¹. ¹H NMR (500 MHz, DMSO-d 6): δ = 6.28 (2 H, s, 2 NH), 6.98-7.11 (2 H, m, 2 CH of Ar), 8.17-8.30 (3 H, m, 3 CH of Ar), 8.85 (1 H, br, CH of Ar), 11.53 (1 H, s, NH), 11.87 (1 H, s, NH), 13.42 (1 H, s, NH). ¹³C NMR (125.7 MHz, DMSO-d 6): δ = 74.2 (Cspiro), 110.9 (C), 111.5 (CH), 115.6 (CH), 116.3 (C), 120.2 (C), 123.9 (CH), 127.6 (CH), 129.8 (CH), 134.7 (CH), 142.2 (C), 142.7 (C), 147.6 (C), 147.0 (C), 150.5 (C), 153.4 (C), 162.9 (C=O), 164.4 (C=O). MS: m/z (%) = 206 (47), 191 (19), 177 (10), 163 (31), 149 (23), 133 (82), 105 (39), 90 (91), 77 (75), 63 (100), 57 (86).
Compound 2f: yield 0.37 g (68%); dark brown powder; mp up 280 ˚C. IR (KBr): 3000-3500 (2 br bands, 5 NH), 1718 (2 NC=O), 1600 (C=N, C=C), 1549 and 1367 (NO2) cm-¹. ¹H NMR (500 MHz, DMSO-d 6): δ = 6.22 (2 H, s, 2 NH), 6.85-6.90 (2 H, m, 2 CH of Ar), 7.39-7.52 (3 H, m, 3 CH of Ar), 8.30 (1 H, br, CH of Ar), 10.95 (1 H, s, NH), 11.35 (1 H, s, NH), 13.36 (1 H, s, NH). ¹³C NMR (125.7 MHz, DMSO-d 6): δ = 74.1 (Cspiro), 112.6 (C), 113.2 (CH), 113.6 (C), 114.1 (CH), 118.1 (C), 121.6 (C), 122.7 (CH), 131.0 (CH), 133.8 (CH), 134.68 (C), 136.07 (CH), 141.54 (C), 144.18 (C), 149.5 (C), 152.2 (C), 162.1 (C=O), 163.8 (C=O). MS: m/z (%) = 551 (6) [M+ + 4], 549 (12), 547 (6), 523 (9), 368 (47), 353 (7), 313 (22), 285 (13), 264 (19), 240 (20), 238 (20), 237 (42), 152 (24), 98 (75), 83 (83), 71 (85), 57 (100).
Compound 2g: yield 0.44 g (60%); orange powder; mp 220 ˚C. IR (KBr): 3437 (br, 3 NH), 1721 (2 NC=O), 1600 (C=N, C=C), 1562 and 1342 (NO2) cm-¹. ¹H NMR (500 MHz, DMSO-d 6): δ = 4.97 (4 H, d, ³ J HH = 14.6 Hz, 2 CH2), 6.27 (2 H, s, 2 NH), 6.93-6.96 (2 H, m, 2 CH of Ar), 7.27-7.34 (10 H, m, 10 CH of Ar), 7.53 (3 H, br, 3 CH of Ar), 8.35 (1 H, br, CH of Ar), 13.41 (1 H, s, NH). ¹³C NMR (125.7 MHz, DMSO-d 6): δ = 42.7 (CH2), 42.8 (CH2), 74.1 (Cspiro), 111.9 (C), 112.6 (C), 114.5 (CH), 115.0 (CH), 117.6 (C), 121.1 (C), 122.7 (C), 127.2 (CH), 127.3 (CH), 127.5 (CH), 127.6 (CH), 128.6 (C), 128.7 (2 CH), 130.9 (CH), 133.7 (C), 133.9 (C), 135.3 (CH), 135.7 (CH), 135.9 (CH), 141.8 (C), 144.2 (C), 148.6 (C), 160.5 (C=O), 162.6 (C=O). MS: m/z (%) = 331 (7), 329 (7), 317 (7), 315 (7), 258 (5), 256 (5), 224 (13), 170 (12), 168 (12), 91 (100), 65 (33).
Compound 2h: yield 0.48 g (63%); dark brown powder; mp 163 ˚C. IR (KBr): 3308 and 3203 (br, 3 NH), 1719 (2 NC=O), 1604 (C=N, C=C), 1557 and 1348 (NO2) cm-¹. ¹H NMR (500 MHz, DMSO-d 6): δ = 2.21 (6 H, s, 2 Me), 4.88 (4 H, br, 2 CH2), 6.23-7.47 (14 H, m, 14 CH of Ar), 8.31 (1 H, s, NH), 10.17 (1 H, s, NH). ¹³C NMR (125.7 MHz, DMSO-d 6): because of insolubility, only some of the resonances are distinguishable including: δ = 20.6 (2 Me), 74.1 (Cspiro), 127.2 (2 CH of Ar), 127.3 (2 CH of Ar), 129.2 (4 CH of Ar). MS: m/z (%) = 410 (5), 368 (7), 341 (8), 279 (7), 236 (11), 213 (6), 173 (18), 149 (42), 127 (38), 105 (25), 97 (70), 83 (74), 69 (100), 57 (97).