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

Abdolali Alizadeh; Nasrin Zohreh

doi:10.1055/s-0031-1290322

LETTER

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;

Abstract

All articles of this category

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

Full Text

References

References and Notes

<A NAME="RD58611ST-1A">1a</A> Nicolaou KC. Vourloumis D. Winssinger N. Baran PS. Angew. Chem. Int. Ed. 2000, 39: 44

<A NAME="RD58611ST-1B">1b</A> Nicolaou KC. Snyder SA. Proc. Natl. Acad. Sci. U.S.A. 2004, 101: 11929

<A NAME="RD58611ST-1C">1c</A> Nicolaou KC. Edmonds DJ. Bulger PG. Angew. Chem. Int. Ed. 2006, 45: 7134

<A NAME="RD58611ST-1D">1d</A> Li JWH. Vederas JC. Science 2009, 325: 161

<A NAME="RD58611ST-1E">1e</A> Gaich T. Baran PS. J. Org. Chem. 2010, 75: 4657

<A NAME="RD58611ST-2">2</A> Edmondson S. Danishefsky SJ. Sepp-Lorenzino L. Rosen N. J. Am. Chem. Soc. 1999, 121: 2147

<A NAME="RD58611ST-3A">3a</A> Trost BM. Jiang C. Synthesis 2006, 369

<A NAME="RD58611ST-3B">3b</A> Williams RM. Cox RJ. Acc. Chem. Res. 2003, 36: 127

<A NAME="RD58611ST-3C">3c</A> Galliford CV. Scheidt KA. Angew. Chem. Int. Ed. 2007, 46: 8748

<A NAME="RD58611ST-3D">3d</A> Marti C. Carreira EM. Eur. J. Org. Chem. 2003, 2209

<A NAME="RD58611ST-3E">3e</A> Lin H. Danishefsky SJ. Angew. Chem. Int. Ed. 2003, 42: 36

<A NAME="RD58611ST-4A">4a</A> Kornet MJ. Thio AP. J Med Chem. 1976, 19: 892

<A NAME="RD58611ST-4B">4b</A> 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

<A NAME="RD58611ST-5">5</A> Dandia A. Singh R. Saha M. Shivpuri A. Pharmazie 2002, 57: 602

<A NAME="RD58611ST-6">6</A> Mishra AD. J. Nepal Chem. Soc. 2009, 24: 49

<A NAME="RD58611ST-7">7</A> Velikorodov AV. Poddubnyi OYu. Kuanchalieva AK. Krivosheev OO. Russ. J. Org. Chem. 2010, 46: 1826

<A NAME="RD58611ST-8A">8a</A> Alizadeh A. Firuzyar T. Mikaeili A. Synthesis 2010, 3913

<A NAME="RD58611ST-8B">8b</A> Alizadeh A. Mikaeili A. Firuzyar T. Helv. Chim. Acta 2011, 94: 1343

<A NAME="RD58611ST-9A">9a</A> Zohreh N. Alizadeh A. Bijanzadeh HR. Zhu LG. J. Comb. Chem. 2010, 12: 497

<A NAME="RD58611ST-9B">9b</A> Zohreh N. Alizadeh A. Tetrahedron 2009, 65: 2684

<A NAME="RD58611ST-9C">9c</A> Alizadeh A. Zohreh N. Zhu LG. Tetrahedron 2009, 65: 268

<A NAME="RD58611ST-9D">9d</A> Alizadeh A. Zohreh N. Helv. Chim. Acta 2010, 93: 1221

<A NAME="RD58611ST-9E">9e</A> Alizadeh A. Zohreh N. Zhu LG. Oskueyan G. Synlett 2011, 2491

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 (C_spiro), 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 (C_spiro), 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 (C_spiro), 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 (C_spiro), 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 (C_spiro), 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 (C_spiro), 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 (C_spiro), 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 (C_spiro), 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).

<A NAME="RD58611ST-11A">11a</A> Jadidi K. Ghahremanzadeh R. Bazgir A. J. Comb. Chem. 2009, 11: 341

<A NAME="RD58611ST-11B">11b</A> Ghahremanzadeh R. Sayyafi M. Ahadi S. Bazgir A. J. Comb. Chem. 2009, 11: 393

<A NAME="RD58611ST-11C">11c</A> Imani Shakibaei G. Feiz A. Khavasi HR. Abolhasani Soorki A. Bazgir A. ACS Comb. Sci. 2011, 13: 96

<A NAME="RD58611ST-11D">11d</A> Ghahremanzadeh R. Ahadi S. Imani Shakibaei G. Bazgir A. Tetrahedron Lett. 2010, 51: 499

<A NAME="RD58611ST-11E">11e</A> Ahadi S. Ghahremanzadeh R. Mirzaei P. Bazgir A. Tetrahedron 2009, 65: 9316