An Improved Sonogashira Coupling Procedure for the Construction of Rigid Aromatic Multifunctional Monomers Bearing 1,3-Substituted Acetylenic Units

Abstract

The efficient synthesis of rigid multifunctional vinylic monomers 1 and 2 from 3,5-dibromobenzene derivatives and propargyl alcohol via the Sonogashira reaction is reported. For example, a series of 3,5-bis(3-hydroxyprop-1-ynl)benzoate ester derivatives have been prepared efficiently using an improved palladium catalyst system. Subsequent hydrolysis and reaction with 4-vinylaniline afforded a new monomer 2 for use in functional macroporous polymer systems. In addition, Sonogashira and Wittig methodologies have been optimised in order to construct successfully an alternative rigid monomer 1 from 3,5-dibromobenzaldehyde.

Key words

Sonogashira reaction - palladium - cross-coupling - organometallic reagents - tri-2-furylphosphine

References

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16

Typical Procedure for the Preparation of 6a: Bisbenzonitriledichloropalladium (75 mg, 0.20 mmol) and copper iodide (25 mg, 0.10 mmol) were added to a dry round bottomed flask which was purged with argon and filled with dry THF (10 mL). Tri-2-furylphoshine (94 mg, 0.40 mmol) and triethylamine (1.1 mL, 7.80 mmol) were added, followed by 3,5-dibromobenzoic acid ethyl ester (1.01 g, 3.30 mmol). The reaction was stirred at r.t. for 20 min. Propargyl alcohol (0.55 g, 9.80 mmol) was added gradually over 20 min, and the reaction was refluxed under argon for 10 h. The residue of palladium salts was filtered and washed with THF. The combined filtrate and washings were evaporated under reduced pressure. The residue was taken up in chloroform (50 mL) and washed with 1 M hydrochloric acid (20 mL) followed by brine (2 × 20 mL). The combined organic layers were dried over sodium sulfate, filtered at the pump and concentrated in vacuo to yield a brown oil. Subsequent purification using column chromatography (SiO₂, 6:4 CH₂Cl₂:EtOAc) afforded a white solid (mp 163-164 °C, 0.351 g, 42%). ¹H NMR (250 MHz, CDCl₃): δ = 1.17 (t, 3 H, J = 7.1 Hz, CH₃), 4.22 (q, 2 H, J = 7.1 Hz, CH₂), 4.42 (s, 4 H, 2 × CH₂), 7.43 (t, 1 H, J = 1.6 Hz, ArH), 7.86 (d, 2 H, J = 1.6 Hz, ArH). ¹³C NMR (67.5 MHz, CDCl₃): δ = 13.2 (CH₃), 50.2 (2 CH₂), 60.6 (CH₂), 82.5 (2 × C≡C), 88.1 (2 × C≡C), 122.3 (2 × ArCH), 129.7 (ArCH), 131.3 (2 × ArC-C), 137.3 (ArC-COOEt), 164.4 (C=O); IR: ν_max 666, 723, 1414, 1462, 1585, 1735, 2354, 2856, 2923 cm^-1; m/z (TOF MS ES+) mobile phase 70:30 CH₃CN:0.05 M NH₄OAc(aq), flow injection: calculated for C₁₅H₁₄O₄ 258.2732, found 792.3010 [3 M + NH₄]⁺, 534.2120 [2 M + NH₄]⁺, 517.1837 [2 M + H]⁺, 481.1641 [2 M + H - 2 H₂O]⁺, 300.1233 [MH + CH₃CN]⁺, 259.0965 [MH⁺].