Interaction of Izatins with Some Five-membered Aminoheterocycles

Abstract

5-Aminopyrazoles react with izatins giving 3-(5-aminopyrazol-3-yl)-3-hydroxy-2-oxindolines in high yield. Analogously izatins react with 5-aminoisoxazole and 2-aminofuran. Under those conditions 2-aminothiophene reacts yielding 3-(thien-2-ylimino)-2-oxindoline.

Key words

electrophilic substitution - aminoheterocycles - pyrazole - isoxazole - furan - thiophene - izatin - combinatorial chemistry - parallel synthesis

References

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• 12a

  Typical spectrum ¹H NMR: 3e (400 MHz, DMSO-D₆): δ = 1.46 (3 H, s, CH₃), 2.84 (2 H, t, CH₂CH₂CN), 4.08 (2 H, t, CH₂CH₂CN), 5.28 (2 H, s, NH₂), 6.69 (1 H, s, OH), 7.17 (1 H, d, ⁴ J = 2.1 Hz, C⁴H), 7.29 (1 H, d, ⁴ J = 2.1 Hz, C⁶H), 10.83 (1 H, s, NH).

• 12b

  Typical spectrum ¹³C NMR: 3e (100 MHz, DMSO-D₆): δ = 13.5, 17.9, 42.4, 75.6 C(3), 97.9 (C4′), 115.4 C(7), 119.4 CN, 124.2 C(4), 127.1 C(5), 129.2 C(6), 137.0 C(3a), 139.0 C(7a), 143.2 C(5′), 147.0 C(3′), 178.5 C(2)=O.

7

General Procedure: Equimolar amounts of aminopyrazole and izatin were mixed and dissolved in warm ethanol
(˜ 40 °C) and a catalytic amount of iodine (˜ 2 mg) was added. The solution was kept at r.t. for 2 h and the precipitated product was isolated by filtration.

8

5: White crystals; yield 54%; mp 249-250 °C; ¹H NMR (400 MHz, DMSO-D₆): δ = 1.52 (3 H, s, CH₃), 6.27 (2 H, s, NH₂), 6.79 (1 H, s, OH), 7.19 (1 H, d, ⁴ J = 2.1 Hz, C⁴H), 7.33 (1 H, d, ⁴ J = 2.1 Hz, C⁶H), 10.94 (1 H, s, NH); ¹³C NMR (100 MHz, DMSO-D₆): δ = 11.0 CH₃, 74.2 C(3), 88.6 C(4′), 115.7 C(7), 124.2 C(4), 127.4 C(5), 129.7 C(6), 135.9 C(3a), 139.1 C(7a), 157.5 C(3′), 168.9 C(5′), 178.0 C(2)=O.

9

7: Starting aminofuran 5 and resulting product are sensitive to oxygen; the reaction was performed under an argon atmosphere. White crystals; yield 27%; mp 196-197 °C; ¹H NMR (400 MHz, DMSO-D₆): δ = 1.22 (3 H, t, CH₃), 4.15 (2 H, q, CH₂), 6.57 (1 H, s, C^{4 ′}H), 6.72 (3 H, broad, NH₂ and OH), 7.45 (1 H, d, ⁴ J = 2.1 Hz, C⁴H), 7.57 (1 H, d, ⁴ J = 2.1 Hz, C⁶H), 11.06 (1 H, s, NH); ¹³C NMR (100 MHz, DMF-d ₇): δ = 15.4 CH₃, 61.0 CH₂, 75.9 C(3), 97.6 C(4′), 116.9 C(7), 122.8 C(3′), 125.5 C(4), 128.7 C(5), 130.6 C(6), 133.5 C(3a), 137.0 C(7a), 140.1 C(2′), 159.3 C=O, 161.4 C(5′), 179.5 C(2)=O.

10

9: Orange crystals; yield 72%; mp 276-277 °C; ¹H NMR (300 MHz, DMSO-D₆): δ = 1.36 (3 H, t, CH₂CH₃), 2.49 (3 H, s, CH₃), 2.31(2 H, q, CH₂CH₃), 7.47 (3 H, s, CH), 11.59 (1 H, s, NH).