Catalytic, Kinetic, and Mechanistic Insights into the Fixation of CO2 with Epoxides Catalyzed by Phenol-Functionalized Phosphonium Salts

Abstract

A series of hydroxy-functionalized phosphonium salts were studied as bifunctional catalysts for the conversion of CO₂ with epoxides under mild and solvent-free conditions. The reaction in the presence of a phenol-based phosphonium iodide proceeded via a first order rection kinetic with respect to the substrate. Notably, in contrast to the aliphatic analogue, the phenol-based catalyst showed no product inhibition. The temperature dependence of the reaction rate was investigated, and the activation energy for the model reaction was determined from an Arrhenius-plot (E_a =39.6 kJ mol^-1 ). The substrate scope was also evaluated. Under the optimized reaction conditions, 20 terminal epoxides were converted at room temperature to the corresponding cyclic carbonates, which were isolated in yields up to 99 %. The reaction is easily scalable and was performed on a scale up to 50 g substrate. Moreover, this method was applied in the synthesis of the antitussive agent dropropizine starting from epichlorohydrin and phenylpiperazine. Furthermore, DFT calculations were performed to rationalize the mechanism and the high efficiency of the phenol-based phosphonium iodide catalyst. The calculation confirmed the activation of the epoxide via hydrogen bonding for the iodide salt, which facilitates the ring-opening step. Notably, the effective Gibbs energy barrier regarding this step is 97 kJ mol^-1 for the bromide and 72 kJ mol^-1 for the iodide salt, which explains the difference in activity.

Keywords: CO2 fixation; cyclic carbonates; homogeneous catalysis; mechanism; organocatalysts.

Scheme 1

Synthesis of cyclic and polycarbonates as well as concepts and selected catalysts for the conversion of epoxides with CO₂.

Figure 1

Comparison of a first‐order kinetic fit and the kinetic model represented in Equation (2) for the conversion of epoxide 1 a with CO₂ in the presence of catalyst 3 and 8. The observed selectivity was >99 %. Reaction conditions: 1,2‐butylene oxide (1 a, 460 mmol), 2 mol % catalyst 3 or 8, p(CO₂)=1.0 MPa, 45 °C, 48 h.

Figure 2

Arrhenius‐plot for the estimation of the activation energy E _a of the conversion of epoxide 1 a with CO₂ in the presence of catalyst 8 over the temperature range of 35–65 °C (T=308.15–338.15 K). Reaction conditions: 1,2‐butylene oxide (1 a, 460 mmol), 2 mol % catalyst 8, p(CO₂)=1.0 MPa. y=−476.5x+13.277, R ²=0.9638.

Figure 3

Substrate scope for the conversion of terminal epoxides 1 into the corresponding carbonates 2. Reaction conditions: 1.0 equiv. 1 (1.00 g), 5 mol % 8, 23 °C, 24 h, p(CO₂)=1.0 MPa, solvent‐free. Isolated yields are given. [a] n‐Butanol was employed as a solvent. [b] Yields were determined by ¹H NMR spectroscopy using mesitylene as internal standard. [c] 80 °C, p(CO₂)=2.5 MPa.

Scheme 2

Synthesis of dropropizine via cyclic carbonate 2 j. Reaction conditions: i) 23 °C, 1 h, H₂O then NaOH/H₂O, 75 °C, 15 min. ii) 5 mol % 8, 23 °C, 48 h, p(CO₂)=1.0 MPa. iii) NaOH/H₂O, 3 h, 23 °C. [a] 45 °C. [b] 45 °C, 24 h.

Figure 4

Substrate scope for the conversion of glycidol and its derivatives 11 into the corresponding carbonates 12. Reaction conditions: 1.0 equiv. 11 (1.00 g), 5 mol % 8, 23 °C, 48 h, p(CO₂)=1.0 MPa, solvent‐free. Isolated yields are given. [a] 24 h. [b] 2 mol % 8, 90 °C, 4 h. [c] 10 mol % 8, 45 °C, n‐butanol as solvent.

Figure 5

Substrate scope for the conversion of internal epoxides 13 into the corresponding carbonates 14. Reaction conditions: 1.0 equiv. 13 (1.00 g), 5 mol % 8, 80 °C, 24 h, p(CO₂)=2.5 MPa, solvent‐free. Isolated yields are given. [a] n‐Butanol was employed as a solvent. [b] 23 °C, p(CO₂)=1.0 MPa. [c] Yields were determined by ¹H NMR spectroscopy using mesitylene as the internal standard.

Figure 6

Molecular structure of catalyst 8 in the solid state. Displacement ellipsoids correspond to 30 % probability. Lower occupancy sites are omitted for clarity. The intermolecular hydrogen bond is shown as dashed line. ^[51]

Scheme 3

Intermediates of the calculated catalytic cycle for ring‐opening at the methylene (C_β, right) and methine carbon (C_α, left) at epoxide 1 a.

Figure 7

Optimized structures for transition states of TS1‐α to TS3‐α as well as TS1‐β to TS3‐β.

Figure 8

Calculated Gibbs free‐energy profile for the addition of CO₂ to epoxide 1 a in the presence of catalyst 8 for the reaction at the methylene (C_β) and methine carbon (C_α).

Figure 9

The three possibilities of the stabilized intermediates Vα (O_a, O_b, and O_c) and the transition states TS3‐α (O_a, O_b, and O_c) in the C_α pathway. The structures of O_b hydrogen bonding interaction have the lowest energy.