Multicomponent Synthesis of 2-[Aryl(arylamino)methyl]furo[3,2-c]pyran-3,4-diones and Diastereoselective Furan Ring Opening to (Z)-3-[3-Aryl-3-(arylamino)acryloyl]-4-hydroxypyran-2-ones

Abstract

An efficient synthesis of novel 2-[aryl(arylamino)methyl]-6-methyl-4H-furo[3,2-c]pyran-3,4(2H)-diones is described by using a three-component reaction of α-bromodehydroaceticacid (α-Br-DHA) with anilines and benzaldehydes. Ammonium acetate is a suitable base to catalyse the diastereoselective tautomerism of the furo[3,2-c]pyran-3,4-diones into (Z)-3-[3-aryl-3-(arylamino)acryloyl]-4-hydroxy-6-methyl-2H-pyran-2-ones by opening the furan ring. These latter compounds were also obtained by a three-component reaction (α-Br-DHA, anilines, benzaldehydes) catalysed by ammonium acetate.

Key words

multicomponent reactions - furan-3-ones - pyran-2-ones - dehydroacetic acid - tautomerism

• References and Notes

• 1a Kashar TI, El-Sehli AH. J. Chem. Pharm. Res. 2013; 5: 474
• 1b Singh K, Sharma PK. Int. J. Pharm. Pharm. Sci. 2014; 6: 345
• 1c Aggarwal R, Rani C, Kumar R, Garg G, Sharma J. ARKIVOC 2014; (ii): 120
• 1d Fadda AA, Amine MS, Arief MM. H, Farahat EK. Pharmacologia 2014; 5: 1
• 2a Perez-Perez MJ, Balzarini J, Rozenski J, De Clercq E, Herdewijn P. Bioorg. Med. Chem. Lett. 1995; 5: 1115
• 2b Bedair AH, El-Hady NA, Abd El-Latif MS, Fakery AH, El-Agrody AM. Farmaco 2000; 55: 708
• 2c Melliou E, Magiatis P, Mitaku S, Skaltsounis AL, Pierre A, Atassi G, Renard P. Bioorg. Med. Chem. 2001; 9: 607
• 2d Aytemir MD, Calis U, Ozalp M. Arch. Pharm. 2004; 337: 281
• 2e Shamroukh AH, Zaki ME. A, Morsy EM. H, Abdel-Motti FM, Abdel-Megeid FM. E. Arch. Pharm. Chem. Life Sci. 2007; 340: 345
• 2f Chabchoub F, Messaad M, Mansour HB, Chekir-Ghedira L, Salem M. Eur. J. Med. Chem. 2007; 42: 715
• 2g Kumar A, Lohan P, Aneja DK, Gupta GK, Kaushik D, Prakash O. Eur. J. Med. Chem. 2012; 50: 81
• 3a Purushothaman KK, Sarada A, Connolly JD. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem. 1984; 23: 611
• 3b El Abbassi M, Essassi EM, Fifani J. Tetrahedron Lett. 1987; 28: 1389
• 3c Rachedi Y, Hamdi M, Speziale V. Synth. Commun. 1989; 19: 3427
• 3d Kherfi HN, Hamdi M, Speziale V. J. Heterocycl. Chem. 1990; 27: 1401
• 3e Nedjar-Kolli B, Hamdi M, Pecher J. Synth. Commun. 1990; 20: 1579
• 3f Rachedi Y, Hamdi M, Sakellariou R, Speziale V. Synth. Commun. 1991; 21: 1189
• 3g Hernández-Galán R, Salvá J, Massanet GM, Collado IG. Tetrahedron 1993; 49: 1701
• 3h Bendaas A, Hamdi M, Sellier N. J. Heterocycl. Chem. 1999; 36: 1291
• 3i Boutemeur-Kheddis B, Hamdi M, Sellier N, Silva AM. S. J. Heterocycl. Chem. 2001; 38: 227
• 3j Makhloufi-Chebli M, Hamdi M, Silva AM. S, Duval O, Helesbeux JJ. J. Heterocycl. Chem. 2009; 46: 18
• 4a Ait Baziz N, Rachedi Y, Hamdi M, Silva AM. S, Belegroune F, Thierry R, Sellier N. J. Heterocycl. Chem. 2004; 41: 587
• 4b Thirupaiah B, Vedula RR. Synth. Commun. 2014; 44: 513
• 4c Abdi Y, Boutemeur-Kheddis B, Hamdi M, Talhi O, Paz FA. A, Kirsch G, Silva AM. S. Synlett 2015; 26: 1749
• 5a Santos CM. M, Silva AM. S, Cavaleiro JA. S. Eur. J. Org. Chem. 2009; 2642
• 5b Tomé SM, Silva AM. S, Santos CM. M. Curr. Org. Synth. 2014; 11: 317
• 5c Sousa JL. C, Talhi O, Rocha DH. A, Pinto DC. G. A, Paz FA. A, Bachari K, Kirsch G, Silva AM. S. Synlett 2015; 26: 2724
• 6a Kanakaraju S, Prasanna B, Chandramouli GV. P. J. Chem. Pharm. Res. 2012; 4: 2994
• 6b Bade T, Vedula RR. Synth. Commun. 2014; 44: 3183
• 6c Pavurala S, Vedula RR. J. Heterocycl. Chem. 2015; 52: 306
• 6d Bade T, Vedula RR. J. Heterocycl. Chem. 2015; 52: 1883
• 7 Karami B, Eskandari K, Khodabakhshi S, Hoseini SJ, Hashemian F. RSC Adv. 2013; 3: 23335
• 8 Adib M, Ansari S, Feizi S, Damavandi JA, Mirzaeic P. Synlett 2009; 3263
• 9 Synthesis of 2-[Aryl(arylamino)methyl)-6-methyl-4H-furo-[3,2-c]pyran-3,4(2H)-diones 4a–h A mixture of 3-(bromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one (1, 0.25 g, 1 mmol) with the appropriate aniline 2 (1 mmol) and benzaldehyde 3 (1 mmol) was stirred in EtOH (5 mL) at reflux for 30 min. The precipitate formed was collected by filtration, washed with EtOH, and then recrystallized from EtOH to give pure compounds 4a–h.
• 10 2-[(4-Chlorophenyl)(p-toluidino)methyl]-6-methyl-4H-furo-[3,2-c]pyran-3,4(2H)-dione (4a) Light yellow solid, 0.37 g (93%), mp 209 °C. ¹H NMR (DMSO-d ₆): δ = 2.09 (s, 3 H, 4′′-CH₃), 2.28 (s, 3 H, 6-CH₃), 4.84 (m, 1 H, H-1a), 5.49 (br s, NH), 5.66 (d, J = 11.5 Hz, 1 H, H-2), 6.37 (s, 1 H, H-7), 6.40 (d, J = 8.1 Hz, 2 H, H-2′′,6′′), 6.77 (d, J = 8.1 Hz, 2 H, H-3′′,5′′), 7.45 (d, J = 8.4 Hz, 2 H, H-2′,6′), 7.56 (d, J = 8.4 Hz, 2 H, H-3′,5′) ppm. ¹³C NMR (DMSO-d ₆): δ = 19.9 (4′′-CH₃), 20.1 (6-CH₃), 58.5 (C-1a), 82.9 (C-2), 98.2 (C-3a), 99.5 (C-7), 112.7 (C-2′′,6′′), 124.9 (C-4′′), 128.3 (C-2′,6′), 129.0 (C-3′,5′), 129.7 (C-3′′,5′′), 133.5 (C-4′), 135.3 (C-1′),145.6 (C-1′′), 145.0 (C-4′) 157.0 (C-7a), 169.1 (C-6), 175.1 (C-4), 187.8 (C-3) ppm. HRMS (ESI⁺): m/z calcd for [C₂₂H₁₈ClNO₄ + Na]⁺: 418.0822; found: 418.0824.
• 11 Synthesis of (Z)-3-[3-Aryl-3-(arylamino)acryloyl]-4-hydroxy-6-methyl-2H-pyran-2-one 5a–h NH₄OAc (1.5 mmol) was added to a mixture of 3-(bromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one (1, 0.25 g, 1 mmol), the appropriate aniline 2 (1 mmol), and benzaldehyde 3 (1 mmol), and then heated to reflux in EtOH (10 mL) for 120 min. The precipitate formed was collected by filtration, washed with EtOH, and then recrystallized from EtOH to give pure compounds 5a–h. Alternatively, compounds 5a–h can be obtained by treating 2-[aryl(arylamino)methyl)-6-methyl-4H-furo[3,2-c]pyran-3,4(2H)-diones 4a–h (1 mmol) with NH₄OAc (1.5 mmol) under stirring in refluxing EtOH (10 mL) for 30 min. The precipitate of compound 5a–h was treated as described above.
• 12 (Z)-3-[3-(4-Chlorophenyl)-3-(p-toluidino)acryloyl]-4-hydroxy-6-methyl-2H-pyran-2-one (5a) Dark yellow solid, 0.38 g (96%), mp 240 °C. ¹H NMR (DMSO-d ₆): δ = 2.36 (s, 3 H, 4′′′-CH₃), 2.76 (s, 3 H, 6-CH₃), 6.53 (s, 1 H, H-5), 6.70 (s, 1 H, H-2′), 7.26 (d, J = 8.3 Hz, 2 H, H-2′′′,6′′′), 7.33 (d, J = 8.3 Hz, 2 H, H-3′′′,5′′′), 7.88 (d, J = 8.4 Hz, 2 H, H-3′′,5′′), 7.88 (d, J = 8.4 Hz, 2 H, H-2′′,6′′), 10.92 (s, 1 H, 3′-NH), 12.13 (s, 1 H, 4-OH) ppm. ¹³C NMR (DMSO-d ₆): δ = 20.6 (4′′′-CH₃), 22.7 (6-CH₃), 85.5 (C-5), 94.8 (C-3), 107.3 (C-2′), 124.7 (C-2′′′,6′′′), 129.0 (C-3′′,5′′), 130.1 (C-3′′′,5′′′), 130.8 (C-1′′), 132.0 (C-2′′,6′′), 133.8 (C-4′′), 134.5 (C-4′′′), 137.1 (C-1′′′), 147.0 (C-3′),162.8 (C-2), 163.2 (C-6), 180.3 (C-4), 180.7 (C-1′) ppm. HRMS (ESI⁺): m/z calcd for [C₂₂H₁₈ClNO₄ + Na]⁺: 418.0822; found: 418.0795.
• 13 Hikem-Oukacha D, Rachedi Y, Hamdi M, Silva AM. S. J. Heterocycl. Chem. 2010; 48: 31
• 14 Rabahi A, Hamdi SM, Rachedi Y, Hamdi M, Talhi O, Paz FA. A, Silva AS. M, Balegroune F, Hamadène M, Taïbi K. J. Mol. Struct. 2014; 1061: 97