Direct C–H Arylation Polymerization to form Anionic Water-Soluble Poly(3,4-ethylenedioxythiophenes) with Higher Yields and Molecular Weights

Abstract

A facile and environmentally benign Pd-catalyzed direct C–H arylation polymerization (DAP) has been developed for the syntheses of homo- and copolymers of anionic-group-functionalized 3,4-ethylenedioxythiophenes with high yields (up to 99%), high molecular weights, and narrow polydispersities. The effects of various Pd catalysts, phosphine ligands, and additives on the properties of the polymers have been examined. The method gives anionic poly(3,4-ethylenedioxythiophenes) with higher molecular weights than those produced by the previously reported chemical or electrochemical methods. The method was also used to synthesize polymers functionalized with carboxylic acid groups without the need for protection/deprotection steps. The resulting polymers can be processed from water or highly polar organic solvents. We also demonstrated a phosphine-free, water-mediated, Pd-catalyzed DAP. The anionic poly(3,4-ethylenedioxythiophenes) were stable in water, and are promising for applications in sensors, drug delivery, and cell engineering.

Key words

polyethylenedioxythiophenes - C–H arylation - palladium catalysis - anionic polymers - step-economic syntheses - polymerization

• References and Notes

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• 17 12-(2,3-Dihydrothieno[3,4-b][1,4]dioxin-2-ylmethoxy)-12-oxododecanoic Acid (C₁₂-EDOT-COOH; 4)A 250 mL two-necked round-bottomed flask was charged with EDOT-OH (1 g, 5.8 mmol), EDAC (2.2 g, 11.6 mmol), DMAP (0.7 g, 5.8 mmol), and dodecanedioic acid (2.7 g, 11.6 mmol), then backfilled with N₂. 1:1 THF–CH₂Cl₂ (30 mL) was added, and the mixture was stirred for 4 h at r.t. The majority of the solvent was removed in a rotary evaporator, and then the residue was dissolved in CH₂Cl₂ and washed with NaHCO₃, brine, and H₂O. The aqueous phase was extracted with CH₂Cl₂ (3×) and this organic phase was dried (MgSO₄) and concentrated. The crude product was purified by a column chromatography [silica gel, hexane–EtOAc (7:3)] to give a white powder; yield: 1.23 g (55%); mp 89–91 °C.IR (KBr): 3673–3296 (br, –OH), 3106 (=C–H), 2930 and 2853 (C–H), 1737 and 1704 (strong, C=O), 1486 cm^–1 (strong, C=C). ¹H NMR (400 MHz, CDCl₃): δ = 6.33 (d, J = 3.6 Hz, 1 H), 6.32 (d, J = 3.8 Hz, 1 H), 4.36–4.32 (m, 1 H), 4.29–4.27 (m, 2 H), 4.20 (dd, J = 11.6, 2.1 Hz, 1 H), 4.01 (dd, J = 11.6, 7.2 Hz, 1 H), 2.35–2.30 (m, 4 H), 1.64–1.56 (m, 4 H), 1.25 (br s, 12 H). ¹³C NMR (100 MHz, CDCl₃): δ = 179.9, 173.7, 141.4, 141.3, 100.3, 100.1, 71.7, 65.8, 62.3, 34.2, 29.5, 29.4, 29.3, 25.0, 24.9. TOF-MS: m/z [M + Na] calcd for C₁₉H₂₈NaO₆S: 407.1504; found: 407.1501.12-[(5,7-Dibromo-2,3-dihydrothieno[3,4-b][1,4]dioxin-2-yl)methoxy]-12-oxododecanoic Acid (4-Br)C₁₂-EDOT-COOH (4; 1 g, 2.6 mmol) was dissolved in THF (15 mL) in a two-neck round-bottomed flask that was backfilled with N₂. The solution was stirred for 15 min then cooled to 0 °C before NBS (1.4 g, 7.8 mmol) was added slowly and the mixture was stirred for a further 4 h at r.t. The solvent was evaporated and the residue was dissolved in CH₂Cl₂ and washed several times with H₂O. The organic layer was then dried (MgSO₄) and concentrated. The crude product was purified by column chromatography [silica gel, EtOAc–hexane (2:3)] to give a yellowish solid; yield: 1.2 g (85%); mp 49–51 °C.¹H NMR (400 MHz, CDCl₃): δ = 4.46–4.37 (m, 2 H), 4.33–4.28 (m, 2 H), 4.11 (dd, 1 H, J = 11.7, 6.4 Hz), 2.40–2.34 (m, 4 H), 1.67–1.60 (m, 4 H), 1.29 (b, s, 12 H). ¹³C NMR (100 MHz, CDCl₃): δ = 179.9, 173.5, 139.4, 139.3, 86.1, 86.0, 72.2, 66.1, 61.8, 34.2, 29.5, 29.4, 29.2, 25.0, 24.9.
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• 19 Poly(C₂-, C₅-, and C₁₂-EDOT-COOH) Polymers; General ProcedureThe polymerization process was similar to that of PEDOTS synthesis by direct C–H arylation polymerization. A N₂-filled 50 mL Schlenk flask was charged with the appropriate EDOT-COOH and 2,5-dibromo-substituted EDOT-COOH monomers, Pd(OAc)₂ (10 mol%), P(p-tol)₃ (10 mol%), Cs₂CO₃ (4 equiv), and anhyd DMF. The mixture was stirred for 36 h at 90 °C, then cooled. The reaction was then quenched with 1:1 H₂O–MeOH, and excess acetone (40 mL) was added. The resulting suspension was centrifuged (5 min, 5000 rpm) and the resulting precipitate was dissolved again in 1:1 H₂O–MeOH and precipitated with acetone. This procedure was repeated until a clear solution was obtained. The precipitate was then dried under vacuum and the product was characterized by means of ¹H NMR and FTIR spectrometry.In agreement with previous reports, the ¹H NMR spectra of the polymers showed broad peaks that were well observed in the zoom mode.Poly(C₂-EDOT-COOH)Dark-blue solid; yield: 140 mg (79%). IR (KBr): 3653–3219 (weak br, OH of acid group), 2915 (weak br, C–H of alkyl groups), 1595 (strong, C=O of carbonyl group), 1519 (strong, C=C of thiophene ring), 1371 (strong, C–C stretching of alkyl groups), 1083 and 1039 cm^–1 (medium bands; asymmetric and symmetric stretching of C–O–C, respectively).Poly(C₅-EDOT-COOH)Blue solid; yield: 145 mg (75%). IR (KBr): 3666–3209 (weak br, OH of acid group), 2930 (weak br, C–H of alkyl groups), 1731 and 1648 (strong, C=O group stretching of ester and acid groups, respectively), 1519 and 1368 (strong, C=C of thiophene ring and alkyl C–C stretching, respectively), 1100 and 1055 cm^–1 (medium bands of asymmetric and symmetric stretching of C–O–C, respectively).Poly(C₁₂-EDOT-COOH): Purple solid; yield: 190 mg (89%). IR (KBr): 3652–3223 (weak and broad, OH of acid group), 2923 and 2852 (strong, C–H of alkyl groups), 1738 and 1657 (strong, C=O stretching of ester and acid groups, respectively), 1569 and 1371 (strong, C=C of thiophene ring and C–C of alkyl stretching, respectively), 1101 and 1051 cm^–1 (medium bands of asymmetric and symmetric stretching of C–O–C, respectively).
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