Bulk Organocatalytic Synthetic Access to Statistical Copolyesters from l-Lactide and ε-Caprolactone Using Benzoic Acid

Abstract

The development of synthetic strategies to produce statistical copolymers based on L-lactide (L-LA) and ε-caprolactone (CL), denoted as P(LA-stat-CL), remains highly challenging in polymer chemistry. This is due to the differing reactivity of the two monomers during their ring-opening copolymerization (ROcP). Yet, P(LA-stat-CL) materials are highly sought-after as they combine the properties of both polylactide PLA and poly(ε-caprolactone) (PCL). Here, benzoic acid (BA), a naturally occurring, cheap, readily recyclable and thermally stable weak acid, is shown to trigger the organocatalyzed ring-opening copolymerization (OROcP) of L-LA and CL under solvent-free conditions at 155 °C, in presence of various alcohols as initiators, with good control over molar masses and dispersities (1.11 <Đ< 1.35) of the resulting copolyesters. Various compositions can be achieved, and the formation of statistical compounds is shown through characterization by 1 H, 13 C and DOSY-NMR spectroscopies and by DSC, as well as through the determination of reactivity ratios (r LA = 0.86, r CL = 0.86), using the visualization of the sum of squared residuals space method. Furthermore, this BA-OROcP process can be exploited to access metal-free PLAb-P(LA-stat-CL)-b-PLA triblock copolymers, using a diol as initiator. Finally, residual traces of BA remaining in P(LA-stat-CL) copolymers (< 0.125 mol%) do not show any cytotoxicity towards hepatocyte-like HepaRG cells, demonstrating the safety of this organic catalyst.As biodegradable, nontoxic and biocompatible polymers, polylactide (PLA) and poly(εcaprolactone) (PCL) can be attractive biosourced surrogates for petroleum-based polymers. 1-4 Both PLA and PCL have been intensively investigated in applications ranging from pharmaceutics to packaging and electronics. 4-7 Yet, both PLA and PCL show some limitations in these applications.For instance, PLA is brittle, exhibits a poor elasticity, 8 a low thermal stability and a modest permeability to drugs. PCL has higher thermal stability and elasticity than PLA, with a glass transition temperature (T g ) around -60 °C vs. 45 -65 °C for PLA, 9,3,10 but suffers from poor mechanical properties. PCL has also a higher permeability to drugs 11 and a half time in vivo of 1year, 12 vs. a few weeks for PLA. 13 As a result, statistical copolymers of lactide (LA) and caprolactone (CL), i.e. P(LA-stat-CL) aliphatic copolyesters, are highly sought-after materials as they combine the strengths and minimize the weaknesses of both homopolymers. P(LA-stat-CL)s have thus attracted a great deal of attention in the biomedical and pharmaceutical fields, 14-18 and as compatibilizers for PLA/PCL blends. 19 The precision synthesis of P(LA-stat-CL) copolymers is still particularly challenging whether organometallic 20 or organic 21-30 catalysts are used. This is due to the highly differing reactivity of the two monomers during ring-opening copolymerization (ROcP). LA is typically incorporated first, although CL gives faster rates than LA in homopolymerization reactions. [21][...

Synthesis of Poly(l-lactide-co-ε-caprolactone) Copolymer: Structure, Toughness, and Elasticity

“…Contreras et al [24] researched the use of zinc diphenyl as initiator to prepare PLCL block copolymers using sequential polymerization, and changed the ratio of comonomers to make them have a low dispersibility and a good ordering. Mezzasalma et al [25] found that using benzoic acid as a catalyst and various alcohols as initiators, PLCL copolymers with good molar mass and dispersibility can be prepared under solvent-free conditions. The elongation at breaking point of the synthesized PLCL copolymer could only reach to 485% [22,26].…”

Copolyesters of ε-caprolactone and l-lactide catalyzed by a tetrabutylammonium phthalimide-N-oxyl organocatalyst

“…34,44 The transesterication reactions might be rather negligible due to the absence of various heterotraids. 34,45 In Fig. 8, a monomodal SEC curve of PCLA suggested the synthesis of block PCLA.…”

“…To date, only few organocatalysts have been reported in the copolymerization in bulk manner. Benzoic acid accompanied with the alcohol initiator was proved to be active for copolymerization of 3-CL and L-LA mixture to obtain the PCLA at 155 C. 34 More than 24 h was required to reach reasonable conversion, apart from which, another equivalent catalyst was added along with the other monomer to obtain block copolymers. The dibenzoylmethane (DBM) was studied to catalyze the PCLA at 155 C, M n of which ranged from 1000 to 4100 g mol À1 , while long reaction time over 48 h was also inevitable.…”

Ultrafast ring-opening copolymerization of lactide with glycolide toward random poly(lactic-co-glycolic acid) copolymers by an organophosphazene base and urea binary catalysts

“…[18][19][20][21][22][23] A series of aliphatic polyesters, including poly(lactide), poly(ε-caprolactone), poly(δ-valerolactone) and poly(γ-butyrolactone), have been successfully achieved with organocatalysts. [24][25][26][27][28][29] Despite the great successes achieved with organocatalysts in the ROP of cyclic lactones or lactides, the organocatalytic preparation of PLGA copolymers has been scarcely explored. Satoh and coworkers achieved the organocatalytic regioselective ring-opening polymerization (ROP) of optically active methylglycolides (MGs) to produce highly alternating PLGAs using an organophosphazene base tBu-P 2 as the catalyst.…”