New Synthesis of 2,3-Diarylxanthones

Clementina M. M. Santos; Artur M. S. Silva; José A. S. Cavaleiro

doi:10.1055/s-2005-921928

LETTER

New Synthesis of 2,3-Diarylxanthones

Clementina M. M. Santos^a,b, Artur M. S. Silva*^b, José A. S. Cavaleiro^b
^a Department of Agro-Industries, Escola Superior Agrária de Bragança, Campus de Santa Apolónia, 5301-855 Bragança, Portugal
^b Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal
Fax: +351(234)370084; e-Mail: arturs@dq.ua.pt;

Abstract

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Abstract

A new synthesis for 2,3-diarylxanthones is described. This was accomplished by aldol condensation of 3-bromo-2-methylchromone with benzaldehydes leading to the formation of 3-bromo-2-styrylchromones, followed by Heck reaction with styrenes.

Key words

diarylxanthones - 2-styrylchromones - Heck reaction - 3-bromo-2-methylchromone - electrocyclisation

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References

<A NAME="RD29105ST-1A">1a</A> Hostettman K. Hostettman M. In Methods in Plant Biochemistry: Plant Phenolics Dey PM. Harbone JB. Academic Press; New York: 1989. Vol. 1: p.493

<A NAME="RD29105ST-1B">1b</A> Bennett GJ. Lee H.-H. Phytochemistry 1989, 28: 967

<A NAME="RD29105ST-2A">2a</A> Abdel-Lateff A. Klemke C. König GM. Wright AD. J. Nat. Prod. 2003, 66: 706

<A NAME="RD29105ST-2B">2b</A> Chiang Y.-M. Kuo Y.-H. Oota S. Fukuyama Y. J. Nat. Prod. 2003, 66: 1070

<A NAME="RD29105ST-2C">2c</A> Pedro M. Cerqueira F. Sousa ME. Nascimento MSJ. Pinto N. Bioorg. Med. Chem. 2002, 10: 3725

<A NAME="RD29105ST-2D">2d</A> Schaper K.-J. Pickert M. Frahm AW. Arch. Pharm. Pharm. Med. Chem. 1999, 332: 91

<A NAME="RD29105ST-2E">2e</A> Minami H. Kinoshita M. Fukuyama Y. Komoda M. Yoshizawa T. Sugiura M. Nakagawa K. Tago H. Phytochemistry 1994, 36: 501

<A NAME="RD29105ST-3">3</A> Fukawa I, Yoneda H, and Asahi KKKK. inventors; Eur. Pat. EP0237004.

<A NAME="RD29105ST-4">4</A> Kelkar AS. Letcher RM. Cheung K.-K. Chiu K.-F. Brown GD. J. Chem. Soc., Perkin Trans. 1 2000, 3732

<A NAME="RD29105ST-5A">5a</A> Cassilas LK. Townsend CA. J. Org. Chem. 1999, 64: 4050

<A NAME="RD29105ST-5B">5b</A> Afzal M. Al-Hassan JM. Heterocycles 1980, 14: 1173

<A NAME="RD29105ST-5C">5c</A> Grover PK. Shah GD. Shah RC. J. Chem. Soc. 1955, 3982

<A NAME="RD29105ST-6">6</A> Mahal HS. Venkataraman K. J. Chem. Soc. 1934, 1767

<A NAME="RD29105ST-7">7</A> Ares JJ. Outt PE. Kakodkar SV. Buss RC. Geiger JC. J. Org. Chem. 1993, 58: 7903

<A NAME="RD29105ST-8">8</A> Ibrahim SS. Ind. Eng. Chem. Res. 2001, 40: 37

<A NAME="RD29105ST-9A">9a</A> Price WA. Silva AMS. Cavaleiro JAS. Heterocycles 1993, 36: 2601

<A NAME="RD29105ST-9B">9b</A> Alonso R. Brossi A. Tetrahedron Lett. 1988, 29: 735

<A NAME="RD29105ST-9C">9c</A> Ayyangar NR. Khan RA. Desphande VH. Tetrahedron Lett. 1988, 29: 2347

Typical Experimental Procedure.
Sodium (0.4 g, 16.7 mmol) was gradually added to 20 mL of dry MeOH and the mixture was stirred until the solution reached r.t. 3-Bromo-2-methylchromone 4 (1 g, 4.2 mmol) and the appropriate benzaldehyde 5a,b (5.0 mmol) were added and the reaction mixture allowed to stand at r.t. for 48 h. After this period, the solution was poured into ice and H₂O and the pH adjusted to 4 with HCl. The yellow solid was removed by filtration, taken up in CH₂Cl₂ and purified by silica gel column chromatography using CH₂Cl₂ as eluent. The solvent was evaporated to dryness and the residue was recrystallised from EtOH to give the 3-bromo-2-styryl-chromones 6a,b in good yields (Table [1] ).

Physical Data of 4′-Benzyloxy-3-bromo-2-styryl-chromone ( 6b).
Mp 176-178 °C. ¹H NMR (300.13 MHz, CDCl₃): δ = 5.09 (s, 2 H, 4′-OCH ₂C₆H₅), 6.99 (d, 2 H, J = 8.8 Hz, H-3′,5′), 7.30 (d, 1 H, J = 15.8 Hz, H-α), 7.34-7.45 (m, 6 H, H-6 and 4′-OCH₂C₆ H ₅), 7.50 (d, 1 H, J = 7.8 Hz, H-8), 7.56 (d, 2 H, J = 8.8 Hz, H-2′,6′), 7.62 (d, 1 H, J = 15.8 Hz, H-β), 7.67 (dt, 1 H, J = 7.8, 1.6 Hz, H-7), 8.19 (dd, 1 H, J = 7.9, 1.6 Hz, H-5). ¹³C NMR (75.47 MHz, CDCl₃): δ = 70.0 (4′-OCH₂C₆H₅), 108.9 (C-3), 115.3 (C-3′,5′), 116.7 (C-α), 117.4 (C-8), 122.0 (C-10), 125.2 (C-6), 126.2 (C-5), 127.4 (C-2,6 of 4′-OCH₂ C ₆H₅), 127.8 (C-1′), 128.1 (C-4 of 4′-OCH₂ C ₆H₅), 128.6 (C-3,5 of 4′-OCH₂ C ₆H₅), 129.7 (C-2′,6′), 133.8 (C-7), 136.3 (C-1 of 4′-OCH₂ C ₆H₅), 139.2 (C-β), 154.7 (C-9), 158.7 (C-2), 160.6 (C-4′), 172.6 (C-4). MS (EI): m/z (rel. int.) = 434 (14) [M^+•, ⁸¹Br], 432 (14) [M^+•, ⁷⁹Br], 388 (8), 234 (7), 205 (8), 92 (15), 91 (100), 65 (9). Anal. Calcd for C₂₄H₁₇BrO₃: C, 66.53; H, 3.95. Found: C, 66.48; H, 4.27.

<A NAME="RD29105ST-12">12</A> Bigi F. Conforti ML. Maggi R. Piccinno A. Sartori G. Green Chem. 2000, 2: 101

<A NAME="RD29105ST-13A">13a</A> Nicolaou KC. Bulger PG. Sarlah D. Angew. Chem. Int. Ed. 2005, 44: 4442

<A NAME="RD29105ST-13B">13b</A> Farina V. Adv. Synth. Catal. 2004, 346: 1553

<A NAME="RD29105ST-13C">13c</A> Reetz MT. de Vries JG. Chem. Commun. 2004, 1559

<A NAME="RD29105ST-13D">13d</A> Heidenreich RG. Köhler K. Krauter JGE. Pietsch J. Synlett 2002, 1118

<A NAME="RD29105ST-13E">13e</A> Biffis A. Zecca M. Basato M. J. Mol. Catal. A: Chem. 2001, 173: 249

<A NAME="RD29105ST-13F">13f</A> de Meijere A. Meyer FE. Angew. Chem., Int. Ed. Engl. 1994, 33: 2379

Typical Experimental Procedure.
A mixture of the appropriate 3-bromo-2-styrylchromone 6a,b (0.6 mmol), PPh₃ (15.7 mg, 0.06 mmol), tetrakis(tri-phenylphosphine)palladium(0) (34.7 mg, 0.03 mmol) and Et₃N (83.6 µL or 334.5 µL, 0.6 or 2.4 mmol) in N-methyl-2-pyrrolidinone (10 mL) was added to styrenes 7a-c (3 mmol). Each reaction was stirred under different conditions of time and temperature according to the substitution of the compounds (Table [2] ). Then, the mixture was poured into H₂O and ice and extracted several times with Et₂O and dried over anhyd Na₂SO₄. The solvent was evaporated and the residue taken up in CH₂Cl₂ and purified by thin layer chromatography (a 7:3 mixture of CH₂Cl₂-light PE as eluent). The product was crystallised from EtOH giving, in each case, the 2,3-diarylxanthones 9a-f (yields described in Table [2] ).

Physical Data of 2,3-Diphenylxanthone ( 8a).
Mp 152-153 °C. ¹H NMR (300.13 MHz, CDCl₃): δ = 7.18-7.29 (m, 10 H, 2,3-C₆ H ₅), 7.41 (dt, 1 H, J = 7.5, 1.0 Hz, H-7), 7.53 (dd, 1 H, J = 8.4, 0.8 Hz, H-5), 7.57 (s, 1 H, H-4), 7.75 (dt, 1 H, J = 7.8, 1.6 Hz, H-6), 8.38 (dd, 1 H, J = 7.9, 1.6 Hz, H-8), 8.38 (s, 1 H, H-1). ¹³C NMR (75.47 MHz, CDCl₃): δ = 118.0 (C-5), 119.5 (C-4), 120.7 (C-9a), 121.9 (C-8a), 124.0 (C-7), 126.8 (C-8), 126.9 (C-4′), 127.6 (C-4′′), 128.0 (C-2′,6′), 128.1 (C-3′′,5′′), 128.4 (C-1), 129.6 (C-2′′,6′′), 129.9 (C-3′,5′), 134.8 (C-6), 137.0 (C-1′), 139.8 (C-2), 139.9 (C-1′′), 147.6 (C-3), 155.2 (C-4a), 156.3 (C-4b), 177.0 (C-9). MS (EI): m/z (rel. int.) = 348 (100) [M^+•], 347 (45), 333 (14), 318 (8), 305 (4), 289 (15), 276 (4), 228 (8), 226 (8), 213 (5), 174 (9), 145 (4), 77 (3). HRMS (EI): m/z calcd for C₂₅H₁₆O₂: 348.1150; found: 348.1158.

Physical Data of 2,3-Diphenyl-3,4-dihydroxanthone ( 10a).
¹H NMR (300.13 MHz, CDCl₃): δ = 3.01 (dd, 1 H, J = 17.4, 1.5 Hz, H-4_trans), 3.67 (dd, 1 H, J = 17.4, 9.0 Hz, H-4_cis), 4.31 (dd, 1 H, J = 9.0, 1.5 Hz, H-3), 7.19-7.30 (m, 8 H, H-2′,3′,4′,5′,6′,3′′,4′′,5′′), 7.32-7.41 (m, 2 H, H-5,7), 7.46-7.50 (m, 2 H, H-2′′,6′′), 7.56 (s, 1 H, H-1), 7.60 (dt, 1 H, J = 7.8, 1.6 Hz, H-6), 8.29 (dd, 1 H, J = 7.9, 1.6 Hz, H-8). ¹³C NMR (75.47 MHz, CDCl₃): δ = 36.7 (C-4), 41.7 (C-3), 116.8 (C-1), 116.9 (C-9a), 118.0 (C-5), 123.9 (C-8a), 125.1 (C-7), 125.7 (C-2′′,6′′), 126.2 (C-8), 127.2 (C-4′), 127.4 (C-2′,6′), 127.6 (C-4′′), 128.5 (C-3′′,5′′), 129.0 (C-3′,5′), 133.0 (C-6), 135.3 (C-1′′), 139.1 (C-1′), 140.7 (C-2), 155.9 (C-4b), 162.5 (C-4a), 174.2 (C-9). MS (FAB⁺): m/z (rel. int.) = 351 (37) [M + H]⁺, 212 (8), 77 (19). HRMS (EI): m/z calcd for C₂₅H₁₈O₂: 350.1307; found: 350.1315.

<A NAME="RD29105ST-17A">17a</A> Clarke DS. Gabbutt CD. Hepworth JD. Heron BM. Tetrahedron Lett. 2005, 46: 5515

<A NAME="RD29105ST-17B">17b</A> de Meijere A. Schelper M. Knoke M. Yucel B. Sünnemann HW. Scheurich RP. Arve L. J. Organomet. Chem. 2003, 687: 249

Santos, C. M. M.; Silva, A. M. S.; Cavaleiro, J. A. S. unpublished results.

Physical Data of 3-Phenyl-2-(4-methoxyphenyl)xanthone ( 8b).
Mp 123-125 °C. ¹H NMR (300.13 MHz, CDCl₃): δ = 3.79 (s, 3 H, 4′-OCH ₃), 6.77 (d, 2 H, J = 8.8 Hz, H-3′,5′), 7.09 (d, 2 H, J = 8.8 Hz, H-2′,6′), 7.20-7.24 (m, 2 H, H-2′′,6′′), 7.26-7.30 (m, 3 H, H-3′′,4′′,5′′), 7.39 (dt, 1 H, J = 7.8, 0.9 Hz, H-7), 7.51 (d, 1 H, J = 8.0 Hz, H-5), 7.53 (s, 1 H, H-4), 7.73 (dt, 1 H, J = 8.0, 1.6 Hz, H-6), 8.34 (s, 1 H, H-1), 8.37 (dd, 1 H, J = 7.8, 1.6 Hz, H-8). ¹³C NMR (75.47 MHz, CDCl₃): δ = 55.2 (4′-OCH₃), 113.4 (C-3′,5′), 118.0 (C-5), 119.5 (C-4), 120.7 (C-9a), 121.9 (C-8a), 123.9 (C-7), 126.7 (C-8), 127.5 (C-4′′), 128.1 (C-1), 128.2 (C-3′′,5′′), 129.6 (C-2′′,6′′), 131.0 (C-2′,6′), 132.1 (C-1′), 134.7 (C-6), 136.7 (C-2), 140.0 (C-1′′), 147.5 (C-3), 155.0 (C-4a), 156.3 (C-4b), 158.6 (C-4′), 177.0 (C-9). MS (EI): m/z (rel. int.) = 378 (100) [M^+•], 363 (12), 347 (9), 334 (7), 318 (3), 305 (9), 292 (2), 276 (4), 263 (2), 213 (3), 189 (5), 173 (3), 167 (5), 138 (3), 92 (2), 77 (2). Anal. Calcd for C₂₆H₁₈O₃: C, 82.52; H, 4.79. Found: C, 82.23; H, 4.94.

Physical Data of 3-(4-Benzyloxyphenyl)-2-(3,4-di-methoxyphenyl)-3,4-dihydroxanthone ( 10f).
¹H NMR (300.13 MHz, CDCl₃): δ = 2.95 (dd, 1 H, J = 17.3, 1.5 Hz, H-4_trans), 3.61 (dd, 1 H, J = 17.3, 8.4 Hz, H-4_cis), 3.83 and 3.84 (2 s, 6 H, 3′,4′-OCH ₃), 4.23 (d, 1 H, J = 8.3 Hz, H-3), 4.94 (s, 2 H, 4′′-OCH ₂C₆H₅), 6.74 (d, 1 H, J = 8.5 Hz, H-5′), 6.84 (d, 2 H, J = 8.7 Hz, H-3′′,5′′), 6.97 (dd, 1 H, J = 8.5, 2.1 Hz, H-6′), 7.09 (d, 1 H, J = 2.1 Hz, H-2′), 7.21 (d, 2 H, J = 8.7 Hz, H-2′′,6′′), 7.28-7.39 (m, 7 H, H-5,7 and H-2,3,4,5,6 of 4′′-OCH₂C₆ H ₅), 7.44 (s, 1 H, H-1), 7.57 (dt, 1 H, J = 7.8, 1.6 Hz, H-6), 8.28 (dd, 1 H, J = 7.9, 1.6 Hz, H-8). ¹³C NMR (75.47 MHz, CDCl₃): δ = 36.7 (C-4), 41.1 (C-3), 55.8 (3′,4′-OCH₃), 69.9 (4′′-OCH₂C₆H₅), 108.7 (C-2′), 110.8 (C-5′), 114.8 (C-1), 115.2 (C-3′′,5′′), 116.9 (C-9a), 118.0 (C-5), 118.3 (C-6′), 123.8 (C-8a), 125.0 (C-7), 126.1 (C-8), 125.7 (C-2,6 of 4′′-OCH₂ C ₆H₅), 127.9 (C-4 of 4′′- OCH₂ C ₆H₅), 128.3 (C-2′′,6′′), 128.5 (C-3,5 of 4′′-OCH₂ C ₆H₅), 132.0 (C-1′), 133.0 (C-6), 133.1 (C-1′′), 135.5 (C-2), 136.9 (C-1 of 4′′-OCH₂ C ₆H₅), 148.7 and 148.8 (C-3′,4′), 155.8 (C-4b), 157.9 (C-4′′), 162.3 (C-4a), 174.2 (C-9). HRMS (EI): m/z calcd for C₃₂H₂₄O₃: 456.1725; found: 456.1735.

The relative stereochemistry of protons H-3 and H-4 is referred as cis and trans.