Amberlyst 15-Catalyzed Efficient Synthesis of 5-Acetyl-4-hydroxy-coumarone and 5-Acetyl-6-hydroxy-coumarone: Crucial Precursors for Several Naturally Occurring Furanoflavones [1]

Abstract

A novel approach to the total synthesis of naturally occurring furanoflavones and furanochalcones is described. Angular and linear furanoflavones and furanochalcones have been prepared in just four steps, using economical reagents and simple reaction conditions. The key step of our approach is the formation of crucial precursors, 5-acetyl-4-hydroxy-coumarone and 5-acetyl-6-hydroxy-coumarone by Amberlyst 15-catalyzed cyclization of phen­oxyacetal.

furanoflavone - furanochalcone - lanceolatin B - isopongaglabol - glabone - pongone - pongamol - ovalitenone

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18

Synthesis of 5-Acetyl-4-hydroxy-coumarone ( 3) and 5-Acetyl-6-hydroxy-coumarone ( 4):
The 1-[4-(2,2-diethoxy-ethoxy)-2-hydroxy-phenyl]-ethanone (20 g, 0.075 mol) was refluxed in dry toluene (30 mL) with Amberlyst 15 (2.5 g) at 120 °C with concurrent removal of water using Dean-Stark trap for 8 h. The resulting reaction mixture was filtered and the resin was washed with excess of toluene. The filtrate thus obtained was concentrated to dryness and two pure compounds were isolated by silica gel column chromatography using EtOAc-hexane (1:10) as eluent, in 92% yield. Coumarone 3: yield 38%; mp 92-93 °C (lit. [12] 92-93 °C). MS (FAB): m/z = 177 [M⁺ + 1]. IR (KBr): 1640 (CO), 3421 (OH) cm^-1. ¹H NMR (200 MHz, CDCl₃): δ = 2.66 (s, 3 H, CH₃), 7.00 (d, J = 2.2 Hz, 1 H, H-3), 7.04 (d, 1 H, J = 8.8 Hz, H-7), 7.57 (d, 1 H, J = 2.2 Hz, H-2), 7.66 (d, 1 H, J = 8.8 Hz, H-6), 13.28 (s, 1 H, OH). Coumarone 4: yield 54%; mp 101-102 °C (lit. [10] 96 °C). MS (FAB): m/z = 177 [M⁺ + 1]. IR (KBr): 1638 (CO), 3426 (OH) cm^-1. ¹H NMR (200 MHz, CDCl₃): δ = 2.70 (s, 3 H, CH₃), 6.72 (d, 1 H, J = 2.2 Hz, H-3), 7.04 (s, 1 H, H-7), 7.56 (d, 1 H, J = 2.2 Hz, H-2), 8.00 (s, 1 H, H-4), 12.40 (s, 1 H, OH).

19

Spectroscopic Data of Other Intermediates and Products. Compound 5: yield 88%; mp 150-151 °C (lit. [9a] 146 °C). MS (FAB): m/z 281 [M⁺ + 1]. IR (KBr): 1606 (CO) cm^-1. ¹H NMR (200 MHz CDCl₃): δ = 6.83 (s, 1 H, CH), 7.01 (d, 1 H, J = 2.2 Hz, H-3), 7.07 (d, 1 H, J = 8.8 Hz, H-7), 7.49-7.54 (m, 3 H, ArH), 7.58 (d, 1 H, J = 2.2 Hz, H-2), 7.73 (d, 1 H, J = 8.8 Hz, H-6), 7.95 (d, 2 H, J = 8.1 Hz, ArH), 13.05 (s, 1 H, OH), 15.45 (s, 1 H, OH). Compound 7: yield 92%; mp 127-128 °C (lit. [4e] 127 °C). MS (FAB): m/z = 263 [M⁺ + 1]. IR (KBr): 1646 (CO) cm^-1. ¹H NMR (200 MHz CDCl₃): δ = 6.90 (s, 1 H, H-3), 7.23 (d, 1 H, J = 2.2 Hz, H-3′′), 7.56-7.60 (m, 4 H, H-6, H-3′,4′,5′), 7.78 (d, 1 H, J = 2.2 Hz, H-2′′), 7.96-8.00 (m, 2 H, H-2′,6′), 8.18 (d, 1 H, J = 8.8 Hz, H-5). Compound 9: yield: 88%; mp 155-156 °C. MS (FAB): m/z = 311 [M⁺ + 1]. IR (KBr): 1606 (CO) cm^-1. ¹H NMR (200 MHz CDCl₃): δ = 3.90 (s, 3 H, OCH₃), 6.74 (d, 1 H, J = 2.2 Hz, H-3), 6.82 (s, 1 H, CH), 7.01 (d, 2 H, J = 9.2 Hz, H-3′ and H-5′), 7.07 (s, 1 H, H-7), 7.55 (d, 1 H, J = 2.2 Hz, H-2), 7.94 (d, 2 H, J = 9.2 Hz, H-2′ and H-6′), 8.04 (s, 1 H, H-4), 12.30 (s, 1 H, OH), 15.64 (s, 1 H, OH). Anal. Calcd for C₁₈H₁₄O₅: C, 69.67; H, 4.55. Found: C, 69.69; H, 4.56. Compound 11: yield 94%; mp 238-239 °C (lit. [7] 170-171 °C). MS (FAB): m/z = 293 [M⁺ + 1]. IR (KBr): 1630 (CO) cm^-1. ¹H NMR (200 MHz CDCl₃): δ = 3.91 (s, 3 H, OCH₃), 6.76 (s, 1 H, H-3), 6.93 (d, 1 H, J = 2.2 Hz, H-3′′), 7.05 (d, 2 H, J = 8.8 Hz, H-3′ and H-5′), 7.44 (s, 1 H, H-8), 7.67 (d, 1 H, J = 2.2 Hz, H-2′′), 7.92 (d, 2 H, J = 8.8 Hz, H-2′ and H-6′), 8.49 (s, 1 H, H-5). Anal. Calcd for C₁₈H₁₂O₄: C, 73.97; H, 4.14. Found: C, 74.06; H, 4.17. Compound 12: yield 91%; mp 208-209 °C (lit. [8] 187-188 °C). MS (FAB): m/z = 293 [M⁺ + 1]. IR (KBr): 1635 (CO) cm^-1. ¹H NMR (200 MHz CDCl₃): δ = 3.91 (s, 3 H, OCH₃), 6.82 (s, 1 H, H-3), 6.92 (d, 1 H, J = 2.2 Hz, H-3′′), 7.09 (d, 1 H, J = 8.2 Hz, H-4′), 7.41-7.57 (m, 3 H, H-2′,H-5′ and H-6′), 7.69 (s, 1 H, H-8), 7.75 (d, 1 H, J = 2.2 Hz, H-2′′), 8.49 (s, 1 H, H-5). Compound 14: yield 85%; mp 129-130 °C (lit. [12] 130 °C). MS (FAB): m/z = 295 [M⁺ + 1]. IR (KBr): 1620 (CO) cm^-1. ¹H NMR (200 MHz CDCl₃): δ = 4.14 (s, 3 H, OCH₃), 6.99 (d, 1 H, J = 2.2 Hz, H-3), 7.16 (s, 1 H, CH), 7.32 (d, 1 H, J = 8.8 Hz, H-7), 7.45-7.51 (m, 3 H, ArH), 7.63 (d, 1 H, J = 2.2 Hz, H-2), 7.87 (d, 1 H, J = 8.8 Hz, H-6), 7.96-8.00 (m, 2 H, ArH), 16.91 (s, 1 H, OH).