Synlett 2013; 24(6): 762-764
DOI: 10.1055/s-0032-1318394
letter
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Unsymmetrical Methylenebisphenol Derivatives

Samuel Guieu*
a   CICECO, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal   Email: rocha@ua.pt
b   QOPNA, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal   Fax: +351(234)370084   Email: sguieu@ua.pt   Email: artur.silva@ua.pt
,
João Rocha
a   CICECO, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal   Email: rocha@ua.pt
,
Artur M. S. Silva*
b   QOPNA, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal   Fax: +351(234)370084   Email: sguieu@ua.pt   Email: artur.silva@ua.pt
› Author Affiliations
Further Information

Publication History

Received: 05 February 2013

Accepted: 17 February 2013

Publication Date:
06 March 2013 (online)


Abstract

A simple and efficient route towards unsymmetrical methylenebisphenol derivatives is reported. This straightforward strategy avoids the use of harmful or dangerous chemicals, allowing the synthesis of highly functionalized bisphenyls with no need of protecting groups. The alkylation of the phenyl ring is selective for the para position of the hydroxyl substituent. All methylenebisphenols were obtained in a completely regioselective manner and isolated in high yields.

Supporting Information

 
  • References and Notes

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  • 14 Typical Experimental Procedure: A catalytic amount of concd H2SO4 (0.1 mL) was slowly added to a solution of 4 or 5 (2.0 mmol) and the desired substituted phenol (2.0 mmol) in glacial AcOH (5 mL) at r.t., and the solution was stirred at 90 °C during 2 h. The reaction mixture was then poured on ice (5 mL) and extracted with CH2Cl2 (3 × 10 mL). The organic layer was washed with sat. NaHCO3, dried over MgSO4, filtrated over silica gel and concentrated under reduced pressure to afford the pure products 3, and 69.
  • 15 Physical Data of 5-(3-Acetyl-4-hydroxybenzyl)-2-hydroxybenzaldehyde (6): white solid; mp 130–132 °C. 1H NMR (300.13 MHz, CDCl3, 25 °C): δ = 12.18 (s, 1 H, OH), 10.92 (s, 1 H, OH), 9.84 (s, 1 H, CHO), 7.51 (d, 4 J H–H = 2.1 Hz, 1 H, aromatic CH), 7.34 (dd, 4 J H–H = 2.1 Hz, 3 J H–H = 8.4 Hz, 1 H, aromatic CH), 7.31 (d, 4 J H–H = 2.1 Hz, 1 H, aromatic CH), 7.28 (dd, 4 J H–H = 2.1 Hz, 3 J H–H = 8.4 Hz, 1 H, aromatic CH), 6.94 (d, 3 J H–H = 8.4 Hz, 1 H, aromatic CH), 6.93 (d, 3 J H–H = 8.4 Hz, 1 H, aromatic CH), 3.93 (s, 2 H, CH2), 2.60 (s, 3 H, Me). 13C NMR (75 MHz, CDCl3, 25 °C): δ = 204.3 (C=O), 196.4 (C=O), 161.0 (COH), 160.1 (COH), 137.5 (CH), 137.1 (CH), 133.1 (CH), 132.2 (Cq), 130.7 (Cq), 130.4 (CH), 120.4 (Cq), 119.5 (Cq), 118.7 (CH), 117.9 (CH), 39.6 (CH2), 26.6 (Me). ESI–MS: m/z = 271.1 [M + H]+. Anal. Calcd for C16H14O4: C, 71.10; H, 5.22. Found: C, 71.23; H, 5.36.
  • 16 Crystal data: C16H14O4, M = 270.27, triclinic, space group P-1, Z = 2, a = 6.9901(6) Å, b = 8.2805(7) Å, c = 11.7324 (9) Å, α = 93.845(4)°, β = 105.754(4)°, γ = 93.618 (4)°, V = 649.77(9) Å3, yellow block with crystal size of 0.40 × 0.20 × 0.06 mm3. Of a total of 3526 reflections collected, 2959 were independent (R int = 0.0540). Final R1 = 0.0627 [I >2σ(I)] and wR2 = 0.1607 (all data). CCDC 923073 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/datarequest/cif.