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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;
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Publication History

Received 21 October 2011
Publication Date:
25 January 2012 (online)

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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

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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).