Highly Branched Poly(α-Methylene-γ-Butyrolactone) from Ring-Opening Homopolymerization

New heteroleptic lanthanide complex [LLaN{Si(CH3)2}] (1) containing tridentate [ONO] ancillary ligand was synthesized from an acid-base ligand exchange reaction with ligands H2L and corresponding homoleptic lanthanide compound La[N{Si(CH3)3}2]3. Meanwhile, dimeric complexes [LLaCl] (2) and [LLaCl] (3) were prepared from salt metathesis reaction between one equivalent of ligands H2L, three equivalent of NaN{Si(CH3)3}2, and one equivalent of LaCl3. These compounds were characterized by nuclear magnetic resonance (300 MHz) and elemental analysis. These complexes were used as catalysts in the ring-opening homopolymerization of α-methylene-γ-butyrolactone. While compound 1 did not show any significant reactivity, compounds 2 and 3 gave significant amount of highly branched poly(α-methylene-γ-butyrolactone) as confirmed by H NMR spectroscopy and Malvern’s triple detector GPCMax analysis in DMSO with molecular weights of over 500,000 Dalton. The glass-transition temperatures of the branched polymer samples were determined using a Dynamic Mechanical Analyzer, DMA Q800.


Introduction
Due to their good mechanical properties, hydrolyzability and biocompatibility, aliphatic saturated polyesters have been extensively investigated with great applications in packaging, drug delivery and medical implantation devices [1]- [10].
The best and most reliable method of synthesizing high molecular weight polyesters is via ring-opening polymerization (ROP) of lactones with a relatively high strain energy using metal initiators for chain-growth polymerization [11]- [35].
Unsaturated polyesters are of high scientific and technological interest for producing tailor-made functionalized biodegradable materials of commercial importance [36] [37] [38].Preferably, they are easily synthesized via ring-opening polymerization (ROP) of unsaturated lactones [38].
Because vinyl-addition is favored over ring-opening at room temperature due to the stability of five membered rings, special conditions and reagents must be used to favor the ring-opening polymerization.In fact, ring-opening copolymerization of α-MBL and other highly strained lactones to obtain unsaturated polyesters have been reported [39] [42] [46].However, the ring-opening homopolymerization of α-MBL has not been reported in the literature.Herein, we report the ring-opening homopolymerization of α-methylene-γ-butyrolactone into highly branched polyester using heteroleptic lanthanide initiators at 0˚C.

Materials and Measurements
All air-or moisture-sensitive reactions were carried out under a dry nitrogen atmosphere, employing standard Schlenk line and glovebox techniques.Anhydrous solvents were purchased and used as received under nitrogen.α-MBL was purchased from Acros, stored under an inert atmosphere, and used as received.Deuterated solvents were purchased from Alfa Aesar and used as received.3,5-di-tert-butyl-2-hydroxybenzaladehyde was purchased from Alfa Aesar while (R)-2-phenylglycinol was purchased from Acros Organic and used as  Gel permeation chromatography (GPC) analyses were performed using Malvern Malvern Viscotek GPCMax TDA 305 triple detection system (refractive index, right angle light scattering, and viscometer).Thermal analysis was done using TA Walters DMA Q800.(R)-(+)-2-phenylglycinol (2.33 g, 0.017 mol) were dissolved in methanol (50 mL).The resulting solution was heated at reflux for 18 h and then cooled to room temperature.Solvent and water were removed using high vacuum Schlenk line to obtain yellow oil.The ligand was purified by column chromatography using hexane-ethyl acetate mixture (9:1) (5.56 g, 92.5 %).[α] D + 0.332 (c = 0.005, toluene).Elemental analysis: (Found: C 76.80, H 9.12, N3. 16

[L I LaCl] (2)
A 100 mL Schlenk flask was obtained and dried in the oven.

1) General polymerization procedure
All materials were prepared in a glovebox and all reactions (air-and moisturesensitive) were carried out in flamed Schlenk-type glassware on a Schlenk line.The monomer/initiator ratio employed was 500:1.In a 25 ml flame dried Schlenk flasks, 1.0 g of the monomer (α-methylene-γ-butyrolactone) was added to the calculated ratio of the catalyst along with 8.0 ml of DMSO.The polymerization reaction was maintained at 0˚C using acetone and ice.After the desired reaction time, the reaction was quenched with 2.0 ml of 5% acidified methanol (HCl/MeOH) and the solid was allowed to precipitate in the freezer (−15˚C) overnight.The white polymer product was filtered, dried and characterized by 1 HNMR spectroscopy (d 6 -DMSO), Gel Permeation Chromatography(DMSO) to obtain polymer microstructure, and molecular weights (M n and M w ), respectively.Thermal analyses of polymer were done using DMA Q800 to obtain Tg.
2) Gel Permeation Chromatography (GPC) data procedure GPC analyses were performed on a Malvern ViscotekGPCMax TDA 305 triple detection system (RI, RALS, and viscometer) using a two mixed bed D6000M columns.Dimethyl Sulfoxide (DMSO) was used as the dissolution solvent and mobile phase at a flow rate of 0.75 mL•min −1 .The temperature of the detectors and columns were set at 50˚C.The calibration method used was triple detection.Samples were dissolved at concentration between 1 -5 mg/mL and dissolved overnight.Allowing for dissolution overnight, the samples were not fully in solution, so heat at 50˚C for 1 hour was applied and the samples were allowed to cool.Samples were filtered through a 0.2 um Nylon syringe filter prior to analysis.
3) Dynamic Mechanical Analyzer (DMA) data procedure Melting temperature, Tm, of polymer samples was done using melting point apparatus while glass transition temperature was obtained using TA Walters Open Journal of Polymer Chemistry Dynamic Mechanical Analyzer, DMA Q800.Tg was obtained as Tan Delta value from DMA Q800 Multi-Frequency-Strain Mode using a powder clamp Temperature Ramp method mounted onto a dual cantilever at 3.00˚C /min from 25˚C to 150˚C and 20.00 µm Amplitude.

Synthesis of Ancillary Ligands
This project discusses the synthesis of cross-linked biodegradable polyesters using new heteroleptic lanthanide catalytic system with three main components LLaX: where L is a chiral dianionic multidentate ancillary ligand, H 2 L I and H 2 L II (see Figure 1), La is a highly electropositive trivalent lanthanum metal and X is an initiator (trimethylsilylamide, chloride) that initiates ring-opening of cyclic ester monomer.In order to initiate ROP, the initiating group, X, must be a good nucleophile and monodentate with labile coordination to lanthanide.The ancillary ligand, L, is to stabilize the metal catalyst during ROP as it remains bound to the lanthanide metal during coordination-insertion mechanism for ROP of lactones.
Newly synthesized ligands H 2 L I and H 2 L II (Figure 1) will be employed as L component in the catalytic system LLaX [41]

Synthesis of Lanthanide Complexes
Attachment of ligands H 2 L I and H 2 L II to homoleptic lanthanum amide offers new heteroleptic metal complexes for metal catalyzed ring-opening polymerization of MBL.A diverse array of synthetic strategies for the different catalyst precursors is proposed from ligand exchange reactions (see Scheme 3) to salt elimination metathesis (see Scheme 4).The synthesis of catalysts via acid-base ligand exchange reaction (Scheme 3) offers a superior, cleaner approach over

Ring-Opening Homopolymerization of MBL Using New Lanthanide Complexes
Unsaturated aliphatic polyesters, which can be synthesized from ROP of naturally available α-methylene-γ-butyrolactone (MBL), are of scientific and Open Journal of Polymer Chemistry of its five-membered ring, copolymerization with ε-CL using lanthanide coordination catalytic system, coupled with appropriate reaction conditions (relatively nonpolar solvent and low temperature at 0˚C to -20˚C) was an effective way of shutting down the vinyl-addition pathway via conjugate addition across the ex Cyclic C=C double bond (ring retention).After carrying out extensive investigations, Hong and Chen also reported that non polar solvents such as toluene was able to suppress the competing vinyl-addition polymerization while copolymerization with a high strain lactone and low reaction temperature favored ROP of the five-membered unsaturated lactones [42].Using similar reaction conditions with newheteroleptic lanthanide complexes LLaX using the ligands H 2 L I and for chain initiation) is illustrated in the mechanism presented in Scheme 6.
Compounds 1, 2, and 3 were treated with MBL and the results are summarised in Table 1 below.All polymerization reactions were performed in DMSO at 0˚C.Entry 1 is the control reaction which shows no polymerization, even after 24 h.Furthermore, there was no polymer formation with compound 1 after 1 hour which is probably due to slow initiation process as a result of bulky amidegroup and non-polymerizability of MBL (Table 1, entry 2).However, compound 2 and 3 gave significant polymer formation after 1 hour (Table 1, entries 3 -4).
All polymerization reactions were quenched with acidified methanol.Due to high solubility of this polymer in DMSO, the reaction flask was kept in freezer overnight to allow precipitation of the white PMBL product.This reactivity suggests that the chloride is better at initiating ROP of MBL than the bulky amide.
1 H NMR analysis of the polymer obtained showed that the methylene protons of exocyclic C=C bond at 5.7 ppm and 6.0 ppm were significantly absent indicative of vinyl addition reactions to form branched polymer (see Figure 3).
GPC analysis of the polymer obtained supports highly branched polyester with a very high molecular weight, about 25 times larger compared to the expected linear unsaturated polyester.The hydrodynamic volume was also very large.Because these compounds were so large compared to expected linear polymers and to ensure reproducibility in analysis since these polymers are novel, a comparison of the samples was repeated with a 73 kDa Dextran polymer standard at different concentrations and the following chromatograms were obtained showing similar molecular weight as previously analyzed (see Figure 4).
All these samples displayed a much larger hydrodynamic size than the 73 kDa Dextran standard.Sample #2 (Table 1, entry 4) showed higher molecular weight of 754 kDa while sample #1 gave 577 kDa (Table 1, entry 3).Both polymeric samples gave a narrow polydispersity of 1.3.The GPC was analyzed using Malvern Viscotek GPCMax triple detector system (refractive index, light scattering and viscometer) which has been proven to successfully determine the absolute molecular weight of polymeric materials.The only explanation to the large molecular weight is the production of highly branched polymer through vinyl addition of the C=C double bonds bringing many linear PMBL polymers into one unit.This is supported by 1 HNMR spectra of the polymers, which showed a significant reduction and in some cases disappearance of the exocyclic CH=CH double bond proton signals.This also explains the difficulty in solubility of these branched polymers.Due to its higher molecular weight, sample #2 gave higher      melting and glass transition temperatures than sample #1 (Figure 5 and Figure 6).The T g for sample #1 was 87.61˚C while that for sample #2 was 123.38˚C.

Conclusion
New heteroleptic lanthanide complexes supported by newly synthesized tridentate dianionic [ONO] aminophenolate ligands were characterized by NMR and Open Journal of Polymer Chemistry  elemental analysis.We also report for the first time, the ring-opening homopolymerization of α-methylene-γ-butyrolactone into highly branched polyester using lanthanide initiators at 0˚C.GPC analysis of the newly synthesized branched polymer gave large molecular weight above 500,000 g/mol and a narrow polydispersity of 1.3.The glass-transition temperatures of the polymer samples were recorded at 87.61˚C and 123.38˚C using a Dynamic Mechanical Analyzer, DMA Q800.The newly synthesized polyester is suitable candidates for medical implantation devices and shape memory materials.

Figure 1 .
Figure 1.New [ONO] ancillary phenolate ligands and intended heteroleptic Lanthanide Catalyst System showing catalytic pocket around metal coordination site.

1 (
Scheme 2. Synthesis of ligand H 2 L II via condensation reaction.

Figure 5 .
Figure 5. DMA Data of newly synthesized branched PMBL showing T g values for entries 3.

Figure 6 .
Figure 6.DMA Data of newly synthesized branched PMBL showing T g values for entries 4.
to initiator ratio.b : M w and M w /M n (PDI) of polymer determined by GPC; PDI = polydispersity index.
3-methyl-1-butanol] was purchased from TCI and used as received.All 1 H and 13 C NMR spectra were recorded on a JEOL-300 NMR spectrometer and referenced to CDCl 3 , C 6 D 6 or C 4 D 8 O. Elemental analyses were performed by Midwest Microlab, Indianapolis, IN.Melting points were obtained on a Mel-Temp apparatus and are uncorrected.Optical rotations were recorded on a Rudolph Autopol III polarimeter with sodium D-line (589 nm) at room temperature.GC-MS analyses were performed on Bruker Scion 436-GC systems at 50˚C with electron impact ionization (70 eV).

Table 1 .
Polymerization of MBL using La complexes at 0˚C.