Synthesis of Novel 1-Aryl-9H-xanthen-9-ones

Abstract

A novel route for the synthesis of 1-aryl-9H-xanthen-9-ones is reported. This methodology involves the condensation of 2-methylchromone with cinnamaldehydes leading to (E,E)-2-(4-arylbuta-1,3-dien-1-yl)-4H-chromen-4-ones. The final steps involved electrocyclization and oxidation of the latter compounds, in an one-pot synthesis, giving the desired 1-aryl-9H-xanthen-9-ones.

Key words

1-arylxanthones - 2-methylchromone - aldol condensation - electrocyclization - oxidation

References and Notes

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18

Typical Experimental Procedure
Sodium (0.11 g, 4.8 mmol) was gradually added to dry EtOH (5 mL), and the mixture was stirred until it reached r.t. 2-Methylchromone (2, 0.2 g, 1.2 mmol) and the appropriate cinammaldehyde 4a-e (1.5 mmol) were added and the reaction mixture allowed to stand at r.t. until complete disappearance of chromone 2 (TLC). The solution was then poured into ice (20 g) and H₂O (30 mL) and adjusted to pH 4 with dilute HCl. The solid was removed by filtration, dissolved in CH₂Cl₂, and purified by silica gel column chromatography using CH₂Cl₂ as eluent. The solvent was evaporated the residue were recrystallized from EtOH to give the (E,E)-2-(4-arylbuta-1,3-dien-1-yl)-4H-chromen-4-ones 5a-e in good yields (Table  [¹] ).

19

Physical Data of ( E , E )-2-[ - 4-(4-methoxyphenyl)buta-1,3-dien-1-yl]-4 H -chromen-4-one (5c)
Mp 137-139 ˚C. ^¹H NMR (300,13 MHz, CDCl₃): δ = 3.84 (s, 3 H, OCH₃), 6.24 (s, 1 H, H-3), 6.32 (d, 1 H, J = 15.3 Hz, H-α), 6.84-6.87 (m, 1 H, H-δ), 6.90 (d, 2 H, J = 8.8 Hz, H-3′,5′), 6.90-6.96 (m, 1 H, H-γ), 7.38 (ddd, 1 H, J = 8.2, 7.1, 0.9 Hz, H-6), 7.41-7.44 (m, 1 H, H-β), 7.43 (d, 2 H, J = 8.8 Hz, H-2′,6′), 7.49 (d, 1 H, J = 8.1 Hz, H-8), 7.67 (ddd, 1 H, J = 8.1, 7.1, 1.7 Hz, H-7), 8.18 (dd, 1 H, J = 8.2, 1.7 Hz, H-5). ^¹³C NMR (75.47 MHz, CDCl₃): δ = 55.3 (OCH₃), 109.9 (C-3), 114.3 (C-3′-5′), 117.7 (C-8), 122.3 (C-α), 124.1 (C-10), 124.8 (C-6), 125.0 (C-γ), 125.5 (C-5), 128.5 (C-2′,6′), 128.6 (C-1′), 133.6 (C-7), 137.8 (C-β), 138.9 (C-δ), 140.4 (C-9), 160.3 (C-4′), 162.0 (C-2), 178.4 (C-4). ESI-MS: m/z (rel. int.) = 305 (100) [M + H]⁺, 327 (110) [M + Na]⁺, 343 (20) [M + K]⁺, 631 (11) [2 M + Na]⁺. Anal. Calcd for C₂₀H₁₆O₃: C, 78.93; H, 5.30. Found: C, 78.86; H, 5.30.

20

Physical Data of 1,4-Dihydro-1-phenyl-9 H -xanthen-9-one (7a)
Yellow oil. ^¹H NMR (300.13 MHz, CDCl₃): δ = 2.76 (ddd, 1 H, J = 18.6, 5.8, 1.3 Hz, H-4 _trans ), 3.01 (ddd, 1 H, J = 18.6, 9.7, 2.8 Hz, H-4 _cis ), 4.56 (d, 1 H, J = 9.7 Hz, H-1), 6.39 (dd, 1 H, J = 9.7, 2.8 Hz, H-2), 6.44-6.51 (m, 1 H, H-3), 7.14-7.26 (m, 3 H, H-3′,4′,5′), 7.33-7.35 (m, 2 H, H-2′,6′), 7.33-7.37 (m, 1 H, H-7), 7.45 (d, 1 H, J = 7.9 Hz, H-5), 7.62 (ddd, 1 H, J = 7.9, 7.7, 1.6 Hz, H-6), 8.17 (dd, 1 H, J = 7.9, 1.6 Hz, H-8). ^¹³C NMR (75.47 MHz, CDCl₃): δ = 31.5 (C-4), 33.4 (C-1), 116.6 (C-9b), 117.9 (C-5), 121.9 (C-2), 124.3 (C-8a), 124.8 (C-7), 125.9 (C-8), 125.9 (C-4′), 127.1 (C-2′,6′), 128.4 (C-3′,5′), 133.1 (C-6), 138.4 (C-3), 143.3 (C-1′), 155.4 (C-4b), 159.3 (C-4a), 176.4 (C-9).

21

Typical Experimental Procedure
Iodine (18 mg, 0.07 mmol) was added to a solution of the appropriated chomone 5a-e (0.35 mmol) in 1,2-4-trichlorobenzene (5 mL), and the mixture was refluxed for 48 h. After this period the solution was directly purified by silica gel column chromatography using light PE as eluent to remove 1,2,4-trichlorobenzene and then CH₂Cl₂ to recover the product. The solvent was evaporated to dryness and the residue were recrystallized from EtOH to give the 1-aryl-9H-xanthen-9-ones 6a-e in moderated yields (Table  [¹] ).

22

Physical Data of 1-Phenyl-9 H -xanthen-9-one (6a)
Mp 177-179 ˚C. ^¹H NMR (300.13 MHz, CDCl₃): δ = 7.18 (dd, 1 H, J = 7.2, 1.2 Hz, H-2), 7.31 (ddd, 1 H, J = 7.8, 7.5, 1.1 Hz, H-7), 7.33-7.36 (m, 2 H, H-2′,6′), 7.41-7.45 (m, 3 H, H-3′,4′,5′), 7.48 (d, 1 H, J = 8.6 Hz, H-5), 7.53 (dd, 1 H, J = 8.4, 1.2 Hz, H-4), 7.67-7.80 (m, 2 H, H-3 and H-6), 8.18 (dd, 1 H, J = 7.8, 1.7 Hz, H-8). ^¹³C NMR (75.47 MHz, CDCl₃): δ = 117.4 (C-5), 117.7 (C-4), 119.3 (C-9b), 122.7 (C-8a), 123.8 (C-7), 127.0 (C-8), 127.1 (C-4′), 127.2 (C-2), 127.5 (C-3′,5′), 128.4 (C-2′,6′), 133.4 (C-3), 134.5 (C-6), 141.8 (C-1′), 144.2 (C-1), 155.4 (C-4b), 157.3 (C-4a), 176.9 (C-9). ESI-MS: m/z (rel. int.) = 273 (100) [M + H]⁺, 295 (76) [M + Na]⁺, 311 (12) [[M + K]⁺, 567 (4) [2 M + Na]⁺. Anal. Calcd for C₁₉H₁₂O₂: C, 83.81; H, 4.44. Found: C, 83.57; H, 4.13.