A Novel and Simple Synthesis of Substituted Anilines by Reaction of 2-Polyfluoroalkylchromones with (Isopropylidene)isopropylamine

Abstract

The reaction of 2-polyfluoroalkylchromones with (isopropylidene)isopropylamine gives N-isopropyl 3-(2-hydroxyaryl)-5-(polyfluoroalkyl)anilines in good to moderate yields.

Key words

chromones - aliphatic ketimines - dinucleophiles - R^F-containing anilines

References

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5

General Procedure for the Synthesis of Anilines(4). A mixture of chromone 1 (15.3 mmol) and imine 2 (33.7 mmol) was refluxed with drying tube for 10 h. Then, the resulting brown liquid was distilled at reduced pressure to give the corresponding aniline 4 as a yellow viscous oil. According to the ¹H NMR and ¹⁹F NMR spectra, compounds 4a-d contained only 1-3% of the starting chromones 1. Spectral and analytical data for selected products follows.
3′-(Isopropylamino)-5-methyl-5′-(trifluoromethyl)[1,1′-biphenyl]-2-ol ( 4b): IR (nujol): 3540, 3400, 1605, 1510
cm^-1. ¹H NMR (400 MHz, CDCl₃/TMS): δ = 1.24 (d, 6 H, 2 CH₃, J = 6.3 Hz), 2.31 (s, 3 H, CH₃), 3.68 (sept, 1 H, CH, J = 6.3 Hz), 3.80 (br s, 1 H, NH), 4.40-5.50 (br s, 1 H, OH), 6.76-6.78 (m, 2 H, H-2′, H-4′), 6.87 (d, 1 H, H-3, ^o J = 8.1 Hz), 6.95 (sext, 1 H, H-6′, ⁴ J _H,H = ⁴ J _H,F = 0.7 Hz), 7.04 (dq, 1 H, H-6, ^m J = 2.2 Hz, ⁴ J _H,CH3 = 0.6 Hz), 7.07 (ddq, 1 H, H-4, ^o J = 8.1 Hz, ^m J = 2.2 Hz, ⁴ J _H,CH3 = 0.6 Hz). ¹⁹F NMR (376 MHz, CDCl₃/C₆F₆): δ = 98.90 (s, CF₃). Anal. Calcd for C₁₇H₁₈F₃NO: C, 66.01; H, 5.87; N, 4.53. Found: C, 66.21; H, 5.96; N, 4.39.
3′-(Isopropylamino)-5′-(1,1,2,2-tetrafluoroethyl)[1,1′-biphenyl]-2-ol ( 4d): IR (nujol): 3530, 3400, 1605, 1515
cm^-1. ¹H NMR (400 MHz, CDCl₃/TMS): δ = 1.25 (d, 6 H, 2 CH₃, J = 6.3 Hz), 3.68 (sept, 1 H, CH, J = 6.3 Hz), 3.80 (br s, 1 H, NH), 5.30 (br s, 1 H, OH), 5.91 (tt, 1 H, CF₂CF₂H, ² J _H,F = 54.1 Hz, ³ J _H,F = 2.8 Hz), 6.72-6.76 (m, 2 H, H-2′,
H-4′), 6.88 (s, 1 H, H-6′), 6.96-7.01 (m, 2 H, H-3, H-5), 7.23-7.29 (m, 2 H, H-4, H-6). ¹⁹F NMR (376 MHz, CDCl₃/C₆F₆): δ = 27.52 (dt, CF₂ CF ₂ H, ² J _F,H = 54.1 Hz, ³ J _F,F = 4.1 Hz), 47.65 (q, CF ₂ CF₂H, ³ J _F,H = ³ J _F,F ca. 3.6 Hz). Anal. Calcd for C₁₇H₁₇F₄NO: C, 62.38; H, 5.23; N, 4.28. Found: C, 62.82; H, 5.54; N, 4.23.