A Novel and Convenient Synthesis of 3-(Polyhaloacyl)chromones Using Diethoxymethyl Acetate

Abstract

The reaction of 2-hydroxy-2-(polyhaloalkyl)chroman-4-ones with diethoxymethyl acetate readily occurs at 140-150 °C for 15 minutes to give 3-(polyhaloacyl)chromones in good yields.

chroman-4-ones - diethoxymethyl acetate - formylation - 3-(polyhaloacyl)chromones

References

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13

General Procedure for the Synthesis of Chromones 2.
A solution of chromanone 1 (1 mmol) in diethoxymethyl acetate (1.0 g, 6 mmol) was heated at 140-150 °C for 15-20 min. After cooling, the resulting mixture was diluted with hexane (3 mL). The solid product obtained on standing was collected by filtration, washed with hexane, and dried. Spectral and analytical data for selected products follows.
3-(Difluoroacetyl)-4 H -chromen-4-one(2a) and 3-(2,2-difluoro-1,1-dihydroxyethyl)-4 H -chromen-4-one ( 3a): IR (KBr): 3076, 1711, 1654, 1614, 1560 cm^-1. ¹H NMR (400 MHz, CDCl₃/TMS): 2a (99%) δ = 6.97 (t, 1 H, CF₂H, ² J _H,F = 53.3 Hz), 7.54 (t, 1 H, H-6, ^o J = 7.6 Hz), 7.57 (d, 1 H, H-8, ^o J = 8.4 Hz), 7.79 (ddd, 1 H, H-7, ^o J = 8.6, 7.2 Hz, ^m J = 1.6 Hz), 8.30 (dd, 1 H, H-5, ^o J = 8.0 Hz, ^m J = 1.6 Hz), 8.68 (s, 1 H, H-2); 3a (1%) δ = 5.47 (s, 2 H, 2 OH), 5.78 (t, 1 H, CF₂H, ² J _H,F = 56.1 Hz), 8.35 (s, 1 H, H-2). ¹⁹F NMR (376 MHz, CDCl₃/C₆F₆): 2a (98%) δ = 30.81 (d, HCF₂, ² J _F,H = 53.3 Hz); 3a (2%) δ = 28.72 (d, HCF₂, ² J _F,H = 56.1 Hz). ¹³C NMR (100 MHz, CDCl₃): 2a δ = 109.03 (t, CF₂, ¹ J _C,F = 247.6 Hz), 118.45, 120.25, 124.74, 126.50, 126.97, 135.10, 155.84, 162.85, 174.42, 186.51 (t, COCF₂, ² J _C,F = 25.6 Hz). Anal. Calcd for C₁₁H₆F₂O₃: C, 58.94; H, 2.70. Found: C, 58.96; H, 2.67.
3-(Trifluoroacetyl)-4 H -chromen-4-one(2c) and 3-(2,2,2-trifluoro-1,1-dihydroxyethyl)-4 H -chromen-4-one ( 3c): ¹H NMR (400 MHz, CDCl₃/TMS): 2c (50%) δ = 7.50-7.58 (m, 2 H, H-6, H-8), 7.79 (ddd, 1 H, H-7, ^o J = 8.6, 7.0 Hz, ^m J = 1.7 Hz), 8.30 (dd, 1 H, H-5, ^o J = 8.0 Hz, ^m J = 1.7 Hz), 8.62 (s, 1 H, H-2); 3c (50%) δ = 6.06 (s, 2 H, 2 OH), 7.50-7.58 (m, 2 H, H-6, H-8), 7.78 (ddd, 1 H, H-7, ^o J = 8.6, 7.0 Hz, ^m J = 1.7 Hz), 8.26 (dd, 1 H, H-5, ^o J = 8.0 Hz, ^m J = 1.7 Hz), 8.40 (s, 1 H, H-2). ¹⁹F NMR (376 MHz, CDCl₃/C₆F₆): 2c (50%) δ = 86.93 (s, CF₃); 3c (50%) δ = 74.85 (s, CF₃). Anal. Calcd for C₁₁H₅F₃O₃·0.25H₂O: C, 53.56; H, 2.25. Found: C, 53.56; H, 2.29.
6-Methyl-3-(trifluoroacetyl)-4 H -chromen-4-one(2d) and 3-(2,2,2-trifluoro-1,1-dihydroxyethyl)-4 H -chromen-4-one ( 3d): IR (KBr): 3309, 3059, 1718, 1664, 1635, 1601, 1558 cm^-1. ¹H NMR (400 MHz, CDCl₃/TMS): 2d (70%) δ = 2.49 (s, 3 H, Me), 7.44 (d, 1 H, H-8, ^o J = 8.6 Hz), 7.57 (ddq, 1 H, H-7, ^o J = 8.6 Hz, ^m J = 2.0 Hz, ⁴ J _H,CH3 = 0.6 Hz), 8.07 (dq, 1 H, H-5, ^m J = 2.0 Hz, ⁴ J _H,CH3 = 0.6 Hz), 8.59 (s, 1 H, H-2); 3d (30%) δ = 2.49 (s, 3 H, Me), 6.16 (s, 2 H, 2 OH), 7.45 (d, 1 H, H-8, ^o J = 8.6 Hz), 7.59 (ddq, 1 H, H-7, ^o J = 8.6 Hz, ^m J = 2.0 Hz, ⁴ J _H,CH3 = 0.6 Hz), 8.02 (dq, 1H, H-5, ^m J = 2.0 Hz, ⁴ J _H,CH3 = 0.6 Hz), 8.37 (s, 1 H, H-2). Anal. Calcd for C₁₂H₇F₃O₃: C, 56.26; H, 2.75. Found: C, 55.98; H, 2.78.
3-(2,2,3,3-Tetrafluoropropanoyl)-4 H -chromen-4-one(2g) and 3-(2,2,3,3-tetrafluoro-1,1-dihydroxypropyl)-4 H -chromen-4-one ( 3g): ¹H NMR (400 MHz, CDCl₃/TMS): 2g (94%) δ = 6.80 (tt, 1 H, CF₂CF₂H, ² J _H,F = 53.3 Hz, ³ J _H,F = 5.8 Hz), 7.54 (ddd, 1 H, H-6, ^o J = 8.0, 7.2 Hz, ^m J = 1.0 Hz), 7.57 (ddd, 1 H, H-8, ^o J = 8.5 Hz, ^m J = 1.0 Hz, ^p J = 0.4 Hz), 7.79 (ddd, 1 H, H-7, ^o J = 8.6, 7.2 Hz, ^m J = 1.7 Hz), 8.27 (ddd, 1 H, H-5, ^o J = 8.0 Hz, ^m J = 1.7 Hz, ^p J = 0.4 Hz), 8.55 (s, 1 H, H-2); 3g (6%) δ = 6.28 (tt, 1 H, CF₂CF₂H, ² J _H,F = 53.2 Hz, ³ J _H,F = 6.2 Hz), 6.31 (s, 2 H, 2 OH), 7.51 (ddd, 1 H, H-6, ^o J = 8.0, 7.2 Hz, ^m J = 1.0 Hz), 7.57 (dd, 1 H, H-8, ^o J = 8.5 Hz, ^m J = 1.0 Hz), 8.23 (dd, 1 H, H-5, ^o J = 8.0 Hz, ^m J = 1.7 Hz), 8.37 (s, 1 H, H-2). ¹⁹F NMR (376 MHz, CDCl₃/C₆F₆): 2g (90%) δ = 24.06 (dt, HCF ₂ CF₂, ² J _H,F = 53.3 Hz, ³ J _F,F = 7.3 Hz), 38.73 (td, HCF₂ CF ₂ , ³ J _F,F = 7.3 Hz, ³ J _F,H = 5.8 Hz); 3g (10%) δ = 25.39 (dt, HCF ₂ CF₂, ² J _F,H = 53.1 Hz, ³ J _F,F = 7.7 Hz), 30.78 (q, HCF₂ CF ₂ , ³ J _F,F = ³ J _F,H = 7.0 Hz). ¹³C NMR (100 MHz, CDCl₃): 2g δ = 109.07 (tt, CF₂, ¹ J _C,F = 252.0 Hz, ² J _C,F = 30.5 Hz), 110.54 (tt, CF₂, ¹ J _C,F = 262.1 Hz, ² J _C,F = 27.4 Hz), 118.40, 120.85, 124.61, 126.39, 127.03, 135.17, 155.69, 162.30 (t, C-2, ⁵ J _C,F = 2.2 Hz), 173.69, 185.58 (t, COCF₂, ² J _C,F = 29.3 Hz). Anal. Calcd for C₁₂H₆F₄O₃: C, 52.57; H, 2.21. Found: C, 52.46; H, 2.24.