Zr(IV) Catalyst for the Ring-Opening Copolymerization of Anhydrides (A) with Epoxides (B), Oxetane (B), and Tetrahydrofurans (C) to Make ABB- and/or ABC-Poly(ester-alt-ethers)

Poly(ester-alt-ethers) can combine beneficial ether linkage flexibility and polarity with ester linkage hydrolysability, furnishing fully degradable polymers. Despite their promising properties, this class of polymers remains underexplored, in part due to difficulties in polymer synthesis. Here, a catalyzed copolymerization using commercially available monomers, butylene oxide (BO)/oxetane (OX), tetrahydrofuran (THF), and phthalic anhydride (PA), accesses a series of well-defined poly(ester-alt-ethers). A Zr(IV) catalyst is reported that yields polymer repeat units comprising a ring-opened PA (A), followed by two ring-opened cyclic ethers (B/C) (−ABB– or −ABC−). It operates with high polymerization control, good rate, and successfully enchains epoxides, oxetane, and/or tetrahydrofurans, providing a straightforward means to moderate the distance between ester linkages. Kinetic analysis of PA/BO copolymerization, with/without THF, reveals an overall second-order rate law: first order in both catalyst and butylene oxide concentrations but zero order in phthalic anhydride and, where it is present, zero order in THF. Poly(ester-alt-ethers) have lower glass-transition temperatures (−16 °C < Tg < 12 °C) than the analogous alternating polyesters, consistent with the greater backbone flexibility. They also show faster ester hydrolysis rates compared with the analogous AB polymers. The Zr(IV) catalyst furnishes poly(ester-alt-ethers) from a range of commercially available epoxides and anhydride; it presents a straightforward method to moderate degradable polymers’ properties.

], synthesis of 1, monomer purification, and polymerizations) were carried out under inert conditions, using standard Schlenk line techniques and a N 2 -filled glovebox, unless otherwise stated. Propylene oxide (PO), butylene oxide (BO), oxetane (OX) were dried by stirring over CaH 2 , followed by fractional distillation, samples were de-gassed by freeze-pump-thaw in triplicate and stored under an inert (N 2 ) atmosphere. 2-Methyltetrahydrofuran (MeTHF), and CDCl 3 were dried by stirring over CaH 2 , followed by vacuum transfer, samples were degassed by freeze-pump-thaw in triplicate and stored over 3 Å molecular sieves under an inert (N 2 ) atmosphere. Tetrahydrofuran (THF), toluene, dichloromethane, chloroform and hexane were purified using an MB SPS800 solvent purification system, solvents were degassed by freezepump-thaw in triplicate and stored over 3 Å molecular sieves under an inert (N 2 ) atmosphere. Phthalic anhydride (PA) was purified by recrystallization from chloroform and sublimation in triplicate. The synthesis of CoK was performed using literature procedures. Pr)]. In each case, the reaction mixture was dried, and recrystallization was attempted with hexane/THF or hexane/DCM mixtures , at -30 °C, to try to isolate pure product. In all cases, yellow powders with the same composition as the crude product were isolated.
The reaction was heated to reflux for 18 h, cooled to RT and concentrated. The yellow residue was dissolved in chloroform (3 mL) and recrystallized to give a yellow gum. The title was product was obtained as a yellow

Sealed vial method:
In a glovebox, the catalyst was weighed into a vial , then dissolved in the required volumes of (co)-monomer to reach the required solution concentration (10 mM in 1 mL). Phthalic anhydride (74 mg, 0.5 mmol) was added to the reaction mixture, the vial sealed, removed from the glovebox and heated to the stipulated temperature (50 °C for catalysis and some control reactions or 80 °C for some control reactions). After the desired time, samples were cooled to 0 °C, taken into the glovebox for removal of aliquots (20 μL) or exposed to air and evaporated to dryness. The crude polymer was characterized as approximately a 10 mg/mL THF solution for GPC and a 10 mg/mL CDCl 3 solution for 1 H NMR spectroscopy. The pure polymer was obtained by precipitation in DCM/MeOH or DCM/Pentane and drying under vacuum at 40 °C, overnight.

ReactIR Spectroscopy method:
In a glovebox, the desired quantity of catalyst and phthalic anhydride were weighed into an ampoule and removed from the glovebox. The ampoule was submerged in an oil bath to 50 °C and cycled three times with vacuum and N 2 and opened to a Schleck line. The ReactIR probe was warmed with a heatgun to remove residual moisture and purged, 10 times using a flow of N 2 from the ampoule, before being set into the vessel and beginning background scans. Finally, butylene oxide (1 mL) was injected into the reaction mixture, and scans were taken every 120 seconds thereafter. After the reaction was completed, the sample was removed from the oil bath and exposed to air. The crude polymer was characterized as approximately a 10 mg/mL THF solution for GPC and a 10 mg/mL CDCl 3 solution for 1 H NMR spectroscopy.

NMR Spectroscopy method:
In a glovebox, the catalyst was weighed into a vial , then dissolved in the required volumes of butylene oxide and tetrahydrofuran stock solutions to reach the required molarity of catalyst (10 mM, total volume = 0.7 mL after mixing, measured with a Hamiltonian syringe). Phthalic anhydride (50 mM) was added to the reaction mixture, the vial sealed and shaken until fully dissolved. The reaction mixture was transferred to a Young Taps NMR tube containing a sealed capillary of mesitylene in C 6 D 6 (0.29 M). The NMR tube was submitted to the instrument preheated to 50°C and analysed by data acquisition every 10 minutes (8 scans, D 1 = 60 s).
Note: The stated D 1 was necessary to resolve and fit epoxide co-solvent integrations, shorter times for D 1 resulted in inferior data fit. Additionally, the epoxide resonances are better resolved when a wide capillary (containing the internal standard, mesitylene) is used.

NMR Spectroscopy Data Handling Procedures, relevant to entries in
As described, monitoring of the reaction was critical to understanding polymer composition. Therefore, an example 1 H NMR spectra, obtained after 1.5 h, from a dried reaction aliquot is presented, as well the related purified product, Figure S8-9. Also, the methods used for calculating the degrees of polymerisation for each monomer are described: The conversion of PA was measured against it's polymeryl species (PA = 7.98 ppm vs P(PA) 7.59 ppm, in pink).
As well a useful indicator of how the reaction was progressing, the percentage of polymerised PA was vital for calculating the DP of other monomers: Next, to calculate the sum of polymerised butylene oxide, the P(PA) integral was set to 4, (the number of protons for 1 equivalent of P(PA)) and integrated against the P(BO) methyl peak (≈ 0.9 ppm). Division of this number by 3, gives relative equivalents of P(BO) in the polymer.      Table 1, P1 (400 MHz, CDCl 3 ).    . c DP of PA measured by integration of the aromatic resonances of PA (7.98 ppm) and P(PA) (7.59 ppm) in the 1 H NMR spectra of crude polymers (Fig. S8). d Determined by integration of the 1 H NMR spectra of purified polymer against P(PA) (Figures S9 and S18). e Determined by gel permeation chromatography (GPC), using THF as the eluent, and calibrated using narrow MW polystyrene standards (Figs. S19). f Theoretical Mn are calculated from the monomer conversion data and assume both iso-propoxides initiate. g Turn over frequency (TOF) = (number of moles of monomer converted/number of moles of catalyst)/hour measured at 1 h.

GPC Data for P1-4 (Table 1)
Figure S19: GPC chromatograms for the polymers described in Table 1 In some cases, the GPC data show a low intensity high molar mass shoulder (<2% overall peak intensity), which is attributed to chains initiated from 1,2-butanediol. The diol forms by hydrolysis of BO. Other authors have written on the propensity for epoxide hydrolysis and the formation of bimodal molar mass distributions in such cases. 4   288: 924, after drying. Data correspond to Table 1, P4 and Figure 3B (400 MHz, CDCl 3 ).  924. Data correspond to Table 1, P4 and Figure 3B.

Polymer Degradation Experiments
To a Schott bottle charged with P1, P4 or poly(PA-alt-BO) (50 mg) was added an aqueous solution of KOH (5 M, 50 mL). The suspension was sealed, heated to 70 °C and stirred using a magnetic stirrer bar, at 1000 rpm.
Aliquots of the suspension for GPC analysis were obtained by cooling the mixture to RT, cutting a piece from the coagulated polymer (approximately 2 mg), washing with water and dissolving in THF. After 7 days, the reaction was quenched wi th HCl until pH 7. In the case of P1 and P4 a completely homogeneous solution was observed.                  Table 2 Figure S48: GPC chromatograms for polymers described in Table 2 Table 2 Figure S51: DSC Thermograms for Polymers P9-12. Data are presented at the glass transition temperatures.

DSC Data for Polymers Described in
Endo Figure S52: DSC thermograms for P13 and 14.

Reaction of 1 and Phthalic Anhydride
In a glovebox, 1 (47 mg, 50 μmol) and phthalic anhydride (15 mg, 100 μmol) were weighed into a vial and dissolved in d 8 -toluene (≈ 0.7 mL). The reaction mixture was transferred to a Young Taps NMR tube, sealed and heated to 80 °C, for 3 hours. 1 H and 19 F NMR spectroscopic analysis was complex, but revealed consumption of