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Synlett 2015; 26(12): 1749-1754
DOI: 10.1055/s-0034-1380214
letter
© Georg Thieme Verlag Stuttgart · New York

A One-Pot Diastereoselective Synthesis of 2-[Aryl(hydroxy)methyl]-6-methyl-2H-furo[3,2-c]pyran-3,4-diones: Crystallographic Evidence for the Furanone Ring Closure

Yamina Abdi
a   Laboratoire de Chimie Organique Appliquée (Groupe Hétérocycles), Faculté de Chimie, Université des Sciences et de la Technologie Houari Boumediène BP 32, El-Alia Bab-Ezzouar, 16111, Alger, Algeria   Email: kheddis.2012@gmail.com
b   Ecole Préparatoire Sciences et Techniques (EPST), BP 474, Place des Martyres, 16000, Alger, Algeria
,
Baya Boutemeur-Kheddis*
a   Laboratoire de Chimie Organique Appliquée (Groupe Hétérocycles), Faculté de Chimie, Université des Sciences et de la Technologie Houari Boumediène BP 32, El-Alia Bab-Ezzouar, 16111, Alger, Algeria   Email: kheddis.2012@gmail.com
,
Maamar Hamdi
a   Laboratoire de Chimie Organique Appliquée (Groupe Hétérocycles), Faculté de Chimie, Université des Sciences et de la Technologie Houari Boumediène BP 32, El-Alia Bab-Ezzouar, 16111, Alger, Algeria   Email: kheddis.2012@gmail.com
,
Oualid Talhi
c   QOPNA, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal   Email: artur.silva@ua.pt
d   Centre de Recherche Scientifique et Technique en Analyses Physico-Chimiques CRAPC, BP 384, Bou-Ismail, 42004, Tipaza, Algeria
,
Filipe A. Almeida Paz
e   CICECO Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal
,
Gilbert Kirsch
f   Laboratoire Structure et Réactivité des Systèmes Moléculaires Complexes, UMR 7565, Université de Lorraine, Avenue du Général Delestraint, 57070 Metz, France
,
Artur M. S. Silva*
c   QOPNA, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal   Email: artur.silva@ua.pt
› Author Affiliations
Further Information

Publication History

Received: 14.03.3015

Accepted after revision: 21 April 2015

Publication Date:
21 May 2015 (online)

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Abstract

Novel furopyran-3,4-dione-fused heterocycles have been obtained by a one-pot reaction of α-brominated dehydroacetic acid and benzaldehydes under organobase conditions. The prepared 2-[aryl(hydroxy)methyl]-6-methyl-2H-furo[3,2-c]pyran-3,4-diones were fully characterized by 2D NMR spectroscopy and supported by single-crystal X-ray analysis to unequivocally prove the furan-3-one five-membered ring-closure mechanism instead of the dihydroflavanon-3-ol six-membered cyclization which has recently been proposed in the literature.

Keywords

furan-3-ones - pyran-2-ones - dehydroacetic acid - synthesis - organobase - 2D NMRspectroscopy - single-crystal X-ray diffraction

Supporting Information

    Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0034-1380214.
  • Supporting Information
 

  • References and Notes

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  • 9 Synthesis of 3-Bromoacetyl-4-hydroxy-6-methyl-2H-pyran-2-one (2) A solution of bromine (0.27 mL, 5 mmol) in AcOH (10 mL) was added portionwise to a solution of DHA (1, 0.84 g, 5 mmol) in AcOH (20 mL). After heating to reflux for 2 h, the reaction mixture was poured into H2O (100 mL) and ice (50 g). The solid obtained was filtered off and recrystallized from a 1:1 mixture of hexane–CHCl3 to afford compound 2. Analytical Data for Compd 2 C8H7BrO4 (yellow crystals, MW = 247.04 g/mol, 0.75 g, 61%; mp 118–119 °C [111–114 °C]7). 1H NMR (300.13 MHz, CDCl3): δ = 2.31 (s, 3 H, 6-CH3), 4.71 (s, 2 H, CH2Br), 6.03 (s, 1 H, H-5), 15.51 (s, 1 H, OH) ppm. 13C NMR (75.47 MHz, CDCl3): δ = 20.8 (6-CH3), 35.2 (CH2Br), 99.4 (C-3), 101.3 (C-5), 160.6 (C-6), 170.1 (C-2), 180.9 (C-4), 197.2 (C-3) ppm. ESI+-MS: m/z = 271 (81Br, 18) [M + Na]+, 269 (79Br, 20) [M + Na]+, 249 (81Br, 90) [M + H]+, 247 (79Br, 95) [M + H]+, 167 (100) [M – Br]+. Anal. Calcd (%) for C8H7BrO4: C, 38.89; H, 2.86. Found: C, 39.10; H, 2.80.
  • 10 Synthesis of 2-[Aryl(hydroxy)methyl]-6-methyl-2H-furo[3,2-c]pyran-3,4-diones 3a–j A suspension of the appropriate benzaldehyde (1 mmol), 3-(bromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one (2, 0.25 g, 1 mmol), and Et3N (0.2 mL, 1.5 mmol) was stirred in EtOH (3 mL) at ambient temperature for 15 min. The powder formed was collected by filtration, washed with H2O and then allowed to dry. The crude compounds thus obtained were recrystallized from EtOH to give pure compounds 3a–j. Representative Analytical Data
    2-[Hydroxy(phenyl)methyl]-6-methyl-2H-furo[3,2-c]pyran-3,4-dione (3a)     C15H12O5 (violet solid, MW = 272.26 g/mol, 0.25 g, 92%; mp 160 °C). 1H NMR (300.13 MHz, DMSO-d 6): δ = 2.34 (s, 3 H, 6-CH3), 5.16 (dd, J = 1.5, 3.7 Hz, 1 H, H-1′), 5.20 (d, J = 1.5 Hz, 1 H, H-2), 5.99 (d, J = 3.7 Hz, 1 H, 1′-OH), 6.69 (s, 1 H, H-7), 7.20–7.41 (m, 5 H, H-2′′3 ′′,4′′,5′′,6′′) ppm. 13C NMR (75.47 MHz, DMSO-d 6): δ = 20.7 (6-CH3), 70.9 (C-1′), 91.4 (C-2), 96.8 (C-7), 99.7 (C-9), 126.2 (C-2′′,6′′), 127.4 (C-4′′), 128.0 (C-3′′,5′′), 140.9 (C-1′′), 155.4 (C-4), 174.1 (C-6), 188.3 (C-8), 192.8 (C-3) ppm. ESI+-HRMS: m/z calcd for [C15H12O5 + Na]+: 295.0582; found: 295.0588. Crystal Data for Compound 3a (C15H12O5)2·H2O, M = 562.51, triclinic, space group P 1, Z = 1, a = 7.1249(5) Å, b = 8.0504(6) Å, c = 12.2442(10) Å, α = 107.237(4)°, β = 96.608(5)°, γ = 102.845(4)°, V = 641.51(9) Å3, μ(Mo-Kα) = 0.112 mm–1, D c = 1.456 g cm–3, red block, crystal size of 0.20 × 0.12 × 0.10 mm3. Of a total of 4402 reflections collected, 2331 were independent (R int = 0.0292). Final R1 = 0.0391 [I > 2σ(I)] and wR2 = 0.0966 (all data). Data completeness to θ = 25.24°, 98.8%; CCDC 1050452. 2-[Hydroxy(3-nitrophenyl)methyl]-6-methyl-2H-furo[3,2-c]pyran-3,4-dione (3b) C15H11NO7 (pale violet solid, MW = 317.25 g/mol, 0.29 g, 91%; mp 208 °C). 1H NMR (??? MHz, DMSO-d 6): δ = 2.35 (s, 3 H, 6-CH3), 5.35–5.36 (m, 2 H, H-1′, H-2), 6.37 (d, J = 6.4 Hz, 1 H, 1′-OH), 6.70 (s, 1 H, H-7), 7.69 (dd, J = 7.8, 7.9 Hz, 1 H, H-5′′), 7.98 (d, J = 7.8 Hz, 1 H, H-6′′) 8.19 (dd, J = 1.7, 7.9 Hz, 1 H, H-4′′), 8.36 (d, J = 1.7 Hz, 1 H, H-2′′) ppm. 13C NMR (75.47 MHz, DMSO-d 6): δ = 20.7 (6-CH3), 69.8 (C-1′), 90.7 (C-2), 96.7 (C-7), 99.7 (C-9), 121.1 (C-2′′), 122.5 (C-4′′), 129.7 (C-5′′), 133.1 (C-6′′), 143.4 (C-1′′), 147.7 (C-3′′), 155.4 (C-4), 174.3 (C-6), 188.2 (C-8), 192.2 (C-3) ppm. ESI+-HRMS: m/z calcd for [C15H11NO7 + Na]+: 340.0433; found: 340.0439. 2-[Hydroxy(2-hydroxyphenyl)methyl]-6-methyl-2H-furo[3,2-c]pyran-3,4-dione (3c) C15H12O6 (grey solid, MW = 288.25 g/mol, 0.27 g, 94%; mp 185 °C). 1H NMR (300.13 MHz, DMSO-d 6): δ = 2.34 (s, 3 H, 6-CH3), 5.11 (d, J = 1.5 Hz, 1 H, H-2), 5.38 (dd, J = 1.5, 4.8 Hz, 1 H, H-1′), 5.76 (d, J = 4.8 Hz, 1 H, 1′-OH), 6.66 (s, 1 H, H-7), 6.81–6.88 (m, 2 H, H-3′′, H-5′′), 7.09–7.17 (m, 1 H, H-4′′), 7.40 (dd, J = 7.7, 1.1 Hz, 1 H, H-6′′), 9.81 (s, 1 H, 2′′-OH) ppm. 13C NMR (75.47 MHz, DMSO-d 6): δ = 20.7 (6-CH3), 66.2 (C-1′), 89.8 (C-2), 96.8 (C-7), 99.8 (C-9), 114.6 (C-3′′), 118.8 (C-5′′), 126.9 (C-6′′), 127.4 (C-1′′), 128.2 (C-4′′), 153.2 (C-2′′), 155.5 (C-4), 173.9 (C-6), 188.4 (C-8), 193.3 (C-3) ppm. ESI+-HRMS: m/z calcd for [C15H12O6 + Na]+: 311.0532; found: 311.0541. 2-[Hydroxy(3-hydroxyphenyl)methyl]-6-methyl-2H-furo[3,2-c]pyran-3,4-dione (3d) C15H12O6 (pale violet solid, MW = 288.25 g/mol, 0.26 g, 90%; mp 205–206 °C). 1H NMR (300.13 MHz, DMSO-d 6): δ = 2.35 (s, 3 H, 6-CH3), 5.07 (dd, J = 1.3, 5.4 Hz, 1 H, H-1′), 5.15 (d, J = 1.3 Hz, 1 H, H-2), 5.91 (d, J = 5.4 Hz, 1 H, 1′-OH), 6.68 (s, 1 H, H-7), 6.70–6.71 (m, 1 H, H-4′′), 6.87–6.90 (m, 2 H, H-2′′, H-6′′), 7.13–7.19 (m, 1 H, H-5′′), 9.41 (s, 1 H, 3′′-OH) ppm. 13C NMR (75.47 MHz, DMSO-d 6): δ = 20.7 (6-CH3), 70.8 (C-1′), 91.5 (C-2), 96.7 (C-7), 99.7 (C-9), 113.3 (C-2′′), 114.3 (C-4′′), 116.7 (C-6′′), 129.1 (C-5′′), 142.5 (C-1′′), 155.4 (C-3′′), 157.2 (C-4), 174.1 (C-6), 188.3 (C-8), 192.9 (C-3) ppm. ESI+-HRMS: m/z calcd for [C15H12O6 + Na]+: 311.0532; found: 311.0535. 2-[Hydroxy(4-chlorophenyl)methyl]-6-methyl-2H-furo[3,2-c]pyran-3,4-dione (3e) C15H11ClO5 (pale yellow solid, MW = 306.69 g/mol, 0.28 g, 91%; mp 268 °C). 1H NMR (300.13 MHz, DMSO-d 6): δ = 2.34 (s, 3 H, 6-CH3), 5.17–5.20 (m, 2 H, H-1′, H-2), 6.10 (d, J = 5.5 Hz, 1 H, 1′-OH), 6.67 (s, 1 H, H-7), 7.44 and 7.52 (2 d, J = 8.5 Hz, 2 × 2 H, H-2′′,3′′, H-5′′,6′′) ppm. 13C NMR (75.47 MHz, DMSO-d 6): δ = 20.7 (6-CH3), 70.2 (C-1′), 91.1 (C-2), 96.7 (C-7), 99.8 (C-9), 128.1 and 128.2 (C-2′′,3′′ and C-5′′,6′′), 132.1 (C-4′′), 140.0 (C-1′′), 155.4 (C-4), 174.2 (C-6), 188.3 (C-8), 192.6 (C-3) ppm. ESI+-HRMS: m/z calcd for [C15H11ClO5 + Na]+: 329.0193; found: 329.0192. 2-[Hydroxy(o-tolyl)methyl]-6-methyl-2H-furo[3,2-c]pyran-3,4-dione (3f) C16H14O5 (red violet solid, MW = 286.27 g/mol, 0.25 g, 87%; mp 207 °C). 1H NMR (300.13 MHz, DMSO-d 6): δ = 2.35 and 2.36 (2 s, 6 H, 2′′-CH3, 6-CH3), 5.12 (d, J = 1.0 Hz, 1 H, H-2), 5.33 (dd, J = 1.0, 5.3 Hz, 1 H, H-1′), 5.87 (d, J = 5.3 Hz, 1 H, 1′-OH), 6.72 (s, 1 H, H-7), 7.16–7.30 (m, 3 H, H-3′′, H-4′′, H-5′′), 77.56 (dd, J = 7.5, 5.3 Hz, 1 H, H-6′′) ppm. 13C NMR (75.47 MHz, DMSO-d 6): δ = 18.5 (2′′-CH3), 20.6 (6-CH3), 67.8 (C-1′), 89.7 (C-2), 96.6 (C-7), 99.6 (C-9), 125.5 (C-5′′), 126.9 (C-6′′), 127.2 (C-3′′), 130.0 (C-4′′), 133.7 (C-2′′), 138.6 (C-1′′), 155.3 (C-4), 174.1 (C-6), 188.3 (C-8), 192.9 (C-3) ppm. ESI+-HRMS: m/z calcd for [C16H14O5 + Na]+: 309.0793; found: 309.0777. 2-[Hydroxy(4-methoxyphenyl)methyl]-6-methyl-2H-furo[3,2-c]pyran-3,4-dione (3g) C16H14O6 (pale brown solid, MW = 302.27 g/mol, 0.27 g, 89%; mp 195 °C). 1H NMR (300.13 MHz, DMSO-d 6): δ = 2.35 (s, 3 H, 6-CH 3), 3.76 (s, 3 H, 4′′-OCH3), 5.11 (dd, J = 1.5, 5.2 Hz, 1 H, H-1′), 5.13 (d, J = 1.5 Hz, 1 H, H-2), 5.89 (d, J = 5.2 Hz, 1 H, 1′-OH), 6.89 (s, 1 H, H-7), 6.94 (d, J = 8.7 Hz, 2 H, H-3′′,5′′), 7.39 (d, J = 8.7 Hz, 2 H, H-2′′,6′′) ppm. 13C NMR (75.47 MHz, DMSO-d 6): δ = 20.7 (6-CH3), 55.1 (4′′-OCH3), 70.6 (C-1′), 91.6 (C-2), 96.8 (C-7), 99.8 (C-9), 113.4 (C-3′′,5′′), 127.5 (C-2′′,6′′), 132.9 (C-1′′), 155.4 (C-4), 158.6 (C-4′′), 174.0 (C-6), 188.2 (C-8), 192.8 (C-3) ppm. ESI+-HRMS: m/z calcd for [C16H14O6 + Na]+: 325.0688; found: 325.0721.
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