Polymerization Of Racemic Lactide Research Articles

Comparison of Imine- and Phosphinimine-Supported Indium Complexes: Tuning the Reactivity for the Sequential and Simultaneous Copolymerization of Lactide and ε-Caprolactone

Imine- and phosphinimine-supported indium complexes were used as catalysts in the polymerization of racemic lactide and ε-caprolactone as well as their copolymerization by the sequential and simultaneous addition of monomers. Tuning the electronics and sterics of the indium centers by either (i) changing the nature of the nitrogen donors and (ii) coordinating a hemilabile side group had a significant effect on the reactivity of the complexes, their stability, and their control in the synthesis of block copolymers. Specifically, the imine-supported complex (5) showed the highest activity in the homo- and copolymerization of the cyclic esters, in contrast to the phosphinimine-supported complex (7), which was significantly slower and less stable. The presence of morpholine and thiomorpholine hemilabile side groups either reduced the activity or prevented the formation of alkoxide complexes.

Alkali and Alkaline Earth Metal Complexes as Versatile Catalysts for Ring‐Opening Polymerization of Cyclic Esters

Biodegradable polyesters such as poly(ϵ-caprolactone) (PCL) and poly(lactic acid) (PLA) have been considered for use in several areas, such as drug delivery devices, sutures, tissue engineering, and GBR membranes, due to its bio-renewability, biodegradability, and biocompatibility. Several synthetic techniques for the preparation of polyesters have been reported in the literature, amongst which the ring-opening polymerization (ROP) of cyclic esters is the most efficient. A convenient approach to access iso-selective PLAs is polymerization of racemic lactide (rac-LA), which shows excellent stereoregularity without the need for costly chiral auxiliaries or ligands. In this personal account, we review a series of methods that have been practiced to the synthesis of biodegradable polyesters from various cyclic monomers using alkali and alkaline earth metal complexes as efficient catalysts.

Syntheses of biodegradable and biorenewable polylactides initiated by aluminum complexes bearing porphyrin derivatives by the ring-opening polymerization of lactides

Three aluminum alkyl complexes bearing porphyrin derivatives were synthesized by pyrrole derivatives and benzaldehyde derivatives. These complexes were characterized by NMR and elemental analysis. These complexes are used for racemic-lactide polymerization. In the ring-opening polymerization of racemic lactide, complex 3(2,3,7,8,12,13,17,18-octamethyl-5,10,15,20-tetraphenylporphyrin aluminum methyl, R1=H, R2=Me in Scheme 2) with isopropanol showed the highest stereoselectivity, and an isotactic polylactide with a Pm of 0.68 was obtained. The polymerization kinetics with complex 3 as catalyst was studied in detail. The kinetics of the polymerization data indicated that the rate of polymerization initiated by complex 3 had first-order dependency on monomer and catalyst. There is a linear relationship between lactide conversion and the number average molecular weight of PLA.

Amphiphilic polylactide‐poly(ethylene oxide)‐poly(propylene oxide) block copolymers: Self‐assembly behavior and cell affinity

ABSTRACTPolylactide (PLA) is a biodegradable polyester recognized for its potential use as a biomedical material. Poly(ethylene oxide) (PEO) and copolymers based on PEO and poly(propylene oxide) (PPO) are biocompatible polyethers widely applied in the biomedical field, particularly as macromolecular nonionic surfactants. In this work, PLA blocks were attached to the PEO and to the PEO and PPO‐based triblock copolymer PEO–PPO–PEO, through ring‐opening polymerization of racemic lactide (rac‐LA) to obtain the amphiphilic triblock PLA–PEO–PLA and pentablock PLA–PEO–PPO–PEO–PLA copolymers containing hydrophilic/hydrophobic blocks with variable block mass ratios. The copolymers were evaluated for chemical composition, molar mass, and thermal properties, and they were used to prepare self‐assemble aggregates in water from tetrahydrofuran polymer solutions. The combination of scattering light experiments and microscopy techniques revealed the spherical morphology of the aggregates with diameters around 180–200 nm, which comprises a hydrophobic PLA core and a hydrophilic polyether shell. The aggregates are nontoxic to human cervical cancer cell line — HeLa cells, as determined by MTS assay, and the aggregates are potential candidates to be applied in the encapsulation of hydrophobic compounds. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 2203–2213

Mechanistic Insight into the Stereochemical Control of Lactide Polymerization by Salan-Aluminum Catalysts.

Alkyl aluminum complexes of chiral salan ligands assembled around the 2,2'-bipyrrolidine core form as single diastereomers that have identical configurations of the N donors. Active catalysts for the polymerization of lactide were formed upon the addition of benzyl alcohol. Polymeryl exchange between enantiomorphous aluminum species had a dramatic effect on the tacticity of the poly(lactic acid) (PLA) in the polymerization of racemic lactide (rac-LA): The enantiomerically pure catalyst of the nonsubstituted salan ligand led to isotactic PLA, and the racemic catalyst exhibited lower stereocontrol. The enantiomerically pure catalyst of the chloro-substituted salan ligand led to PLA with a slight tendency toward heterotacticity, whereas the racemic catalyst led to PLA of almost perfect heterotacticity following an insertion/auto-inhibition/exchange mechanism.

Mechanistic Insight into the Stereochemical Control of Lactide Polymerization by Salan–Aluminum Catalysts

AbstractAlkyl aluminum complexes of chiral salan ligands assembled around the 2,2′‐bipyrrolidine core form as single diastereomers that have identical configurations of the N donors. Active catalysts for the polymerization of lactide were formed upon the addition of benzyl alcohol. Polymeryl exchange between enantiomorphous aluminum species had a dramatic effect on the tacticity of the poly(lactic acid) (PLA) in the polymerization of racemic lactide (rac‐LA): The enantiomerically pure catalyst of the nonsubstituted salan ligand led to isotactic PLA, and the racemic catalyst exhibited lower stereocontrol. The enantiomerically pure catalyst of the chloro‐substituted salan ligand led to PLA with a slight tendency toward heterotacticity, whereas the racemic catalyst led to PLA of almost perfect heterotacticity following an insertion/auto‐inhibition/exchange mechanism.

Role of aggregation in the synthesis and polymerization activity of SalBinap indium alkoxide complexes.

The reaction of racemic SalBinap ligand, (±)-H2(ONN*OMe), with InCl3 and excess NaOEt generated a mixture of two dinuclear compounds [(μ-κ(2)-ONN*OMe)In(μ-OEt)]2 (1a) and [κ(4)-ONN*OMe)In(μ-OEt)]2 (1b), which were isolated and fully characterized. Polymerization of racemic lactide with 1a and 1b was slow in refluxing THF and showed only modest stereoselectivity. Catalyst 1b displayed better control than 1a, with the experimental molecular weights of the resulting poly(lactic acid) in agreement with the expected values. The higher-than-expected molecular weights observed in polymers formed by 1a were due to partial initiation of the catalyst. The reaction of (±)-H2(ONN*OtBu) with InCl3 yielded (κ(4)-ONN*OtBu)InCl (2); however, further reactivity of the compound formed a mixture of products. An attempt to prevent aggregation by reacting (±)-H2(ONN*OMe) with InCl3 and excess NaO(i)Pr yielded an intractable mixture, including [(μ-κ(2)-ONN*OMe)In]2(μ-Cl)(μ-OH) (3). The thermal stabilities of compounds 1a and 1b under polymerization conditions were investigated. Examination of the polymerization behavior of complexes 1a and 1b and the reaction equilibrium between the two illustrates the importance of aggregation in indium salen complexes compared to their aluminum counterparts.

The influence of organosuperbases on the structure and activity of dialkylgallium alkoxides in the polymerization of rac‐lactide: the road to stereo diblock PLA copolymers

Stereoselective polymerization of rac‐lactide is one of the most important issues as the properties of polylactide (PLA) depend strongly on its tacticity. There is, however, a paucity of catalysts that allow for easy switching between heteroselectivity and isoselectivity, which limits the synthesis of stereo copolymers of PLA and modification of polylactide properties. Dialkylgallium alkoxides activated by organosuperbases have been used as catalysts in the ring‐opening polymerization of racemic lactide (rac‐LA). The reaction of (S,S)‐[Me2Ga(μ‐OCH(Me)CO2Me)]2 (1) with 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) or 7‐methyl‐1,5,7‐triazabicyclo[4.4.0]dec‐5‐ene (MTBD) resulted in the formation of isoselective gallium species, highly active in the polymerization of rac‐LA. DOSY (diffusion‐ordered spectroscopy) NMR was indicative for the presence of dimeric gallium species. However, the structure of model monomeric gallium alkoxide Me2Ga(ON) (where ON is monoanionic bidentate ligand possessing organosuperbase functionality) shows that the presence of an organosuperbase may substantially weaken Ga−Oalkoxide−Ga bridges. The facile switch of stereoselectivity upon addition of organosuperbase to nonselective/heteroselective 1 allowed for the first time the synthesis of diblock polylactide comprised of isotactically and heterotactically enriched blocks. Copyright © 2013 John Wiley & Sons, Ltd.

Bulk polymerization of rac-lactide initiated by guanidinate alkoxide complexes of rare earth metals. The molecular structure of the cluster [{(Me3Si)2NC(NPri)2}Nd]4(μ3-OPri)8Li7(μ2-Cl)3(μ3-Cl)2(μ4-Cl)2

The complexes {(Me3Si)2NC(NPri)2}2LnOBut (Ln = Y (1), Lu (2)) initiate the bulk polymerization of racemic lactide (LA) at 130 °C. At the monomer: initiator molar ratio ([LA]: 1) equal to 1000: 1, the quantitative conversion of the monomer is achieved within 6 h. The resulting polymers are characterized by a rather narrow monomodal molecular weight distribution (M w/M n = 1.46–1.82) and molecular weights up to 33400 g mol−1. The molecular weights of the resulting polylactides measured by gel permeation chromatography are 3–11 times lower than the values calculated from the monomer: initiator ratio on the assumption of one growing polymer chain per catalytic center. The reaction of the in-situ prepared complex [(Me3Si)2NC(NPri)2]NdCl2 with 2 equiv. of PriOLi produced the 11-nuclear cluster [{(Me3Si)2NC(NPri)2}Nd]4(μ3-OPri)8Li7(μ2-Cl)3(μ3-Cl)2(μ4-Cl)2 (3), which was isolated in 62% yield. The structure of compound 3 was established by X-ray diffraction. Complex 3 initiates both the bulk and solution polymerization of rac-lactide. In the bulk polymerization at the molar ratio [LA]: [Nd] = 500: 1, the 89% conversion of the monomer was achieved within one hour. The polylactide thus synthesized has the molecular weight M n = 19720 g mol−1 and a rather narrow polydispersity M w/M n = 1.54.

固定化ホモサレン配位子の合成とラセミラクチドの立体選択的重合反応への応用

固定化ホモサレン配位子の合成とラセミラクチドの立体選択的重合反応への応用

Mechanism of Living Lactide Polymerization by Dinuclear Indium Catalysts and Its Impact on Isoselectivity

A family of racemic and enantiopure indium complexes 1-11 bearing bulky chiral diaminoaryloxy ligands, H(NNO(R)), were synthesized and fully characterized. Investigation of both the mono- and the bis-alkoxy-bridged complexes [(NNO(R))InX](2)[μ-Y][μ-OEt] (5, R = (t)Bu, X = Y = Cl; 8, R = Me, X = I, Y = OEt) by variable temperature, 2D NOESY, and PGSE NMR spectroscopy confirmed dinuclear structures in solution analogous to those obtained by single-crystal X-ray crystallography. The dinuclear complexes in the family were highly active catalysts for the ring-opening polymerization (ROP) of lactide (LA) to form poly(lactic acid) (PLA) at room temperature. In particular, complex 5 showed living polymerization behavior over a large molecular weight range. A detailed investigation of catalyst stereoselectivity showed that, although (R,R/R,R)-5 is highly selective for l-LA, only atactic PLA is obtained in the polymerization of racemic LA. No such selectivity was observed for complex 8. Importantly, the selectivities obtained for the ROP of racemic LA with (R,R/R,R)-5 and (R,R/R,R)-8 are different and, along with kinetics investigations, suggest a dinuclear propagating species for these complexes.

Lanthanide Borohydride Complexes of Bulky Guanidinate Ligands [(Me3Si)2NC(N‐Cy)2]2Ln(μ‐BH4)2Li(THF)2 (Ln = Nd, Sm, Yb): Synthesis, Structure and Catalytic Activity in Lactide Polymerization

AbstractA series of new lanthanide borohydride complexes supported by bulky guanidinate ligands [(Me3Si)2NC(N‐Cy)2]2Ln(μ‐BH4)2Li(THF)2 [Ln = Nd (1), Sm (2), Yb (3)] was synthesized by the reaction of related tris(borohydride)s Ln(BH4)3(THF)2 with a twofold molar excess of [(Me3Si)2NC(N‐Cy)2]Li in toluene at 65 °C. The complexes were isolated after recrystallization from hexane in 66, 64, and 68 % yield, respectively. X‐ray diffraction studies revealed that compounds 1–3 are heterodimetallic complexes that have two borohydride ligands μ‐bridging the lanthanide and lithium atoms. Those compounds, especially neodymium complex 1, act as monoinitiators for the ring‐opening polymerization of racemic lactide, providing atactic polymers with a good degree of control, that is, controlled molecular weights and relatively narrow polydispersities (1.09 < Mw/Mn < 1.77), provided moderate substrate‐to‐initiator ratios are used. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Stereoselective Ring‐Opening Polymerization of a Racemic Lactide by Using Achiral Salen– and Homosalen–Aluminum Complexes

Highly isotactic polylactide or poly(lactic acid) is synthesized in a ring-opening polymerization (ROP) of racemic lactide with achiral salen- and homosalen-aluminum complexes (salenH(2)=N,N'-bis(salicylidene)ethylene-1,2-diamine; homosalenH(2)=N,N'-bis(salicylidene)trimethylene-1,3-diamine). A systematic exploration of ligands demonstrates the importance of the steric influence of the Schiff base moiety on the degree of isotacticity and the backbone for high activity. The complexes prepared in situ are pure enough to apply to the polymerizations without purification. The crystal structures of the key complexes are elucidated by X-ray diffraction, which confirms that they are chiral. However, analysis of the (1)H and (13)C NMR spectra unambiguously demonstrates that their conformations are so flexible that the chiral environment of the complexes cannot be maintained in solution at 25 degrees C and that the complexes are achiral under the polymerization conditions. The flexibility of the backbone in the propagation steps is also documented. Hence, the isotacticity of the polymer occurs due to a chain-end control mechanism. The highest reactivity in the present system is obtained with the homosalen ligand with 2,2-dimethyl substituents in the backbone (ArCH==NCH(2)CMe(2)CH(2)N==CHAr), whereas tBuMe(2)Si substituents at the 3-positions of the salicylidene moieties lead to the highest selectivity (P(meso)=0.9(8); T(m)=210 degrees C). The ratio of the rate constants in the ROPs of racemic lactide and L-lactide is found to correlate with the stereoselectivity in the present system. The complex can be utilized in bulk polymerization, which is the most attractive in industry, although with some loss of stereoselectivity at high temperature, and the afforded polymer shows a higher melting temperature (P(meso)=0.9(2), T(m) up to 189 degrees C) than that of homochiral poly(L-lactide) (T(m)=162-180 degrees C). The "livingness" of the bulk polymerization at 130 degrees C is maintained even at a high conversion (97-98 %) and for an extended polymerization time (1-2 h).

Synthesis and structural characterization of two five coordinate aluminum alkyl and bis(trimethylsilyl)amino complexes bearing acyclic tetradentate Schiff bases

Two acyclic Schiff-base ligands, bis-5,5′-(1,3-propanediyldiimino)-2,2-dimethyl-4-hexene-3-one and bis-5,5′-(1,3-ethanediyldiimino)-2,2-dimethyl-4-hexene-3-one, were used to complex homoleptic triethylaluminum and tris[bis(trimethylsilyl)amino]aluminum, respectively. The acid–base reactions proceeded in excellent yields with elimination of ethane or bis(trimethylsilyl)amine during in situ deprotonation of the protio Schiff-base. The colorless aluminum complexes crystallized from n-pentane and were characterized by standard methods including single crystal X-ray diffraction. Polymerization of racemic lactide, with addition of alcohol, yielded PLA with narrow polydispersities but low molecular weights.

Remarkable stereocontrol in the polymerization of racemic lactide using aluminum initiators supported by tetradentate aminophenoxide ligands.

A new family of aluminum complexes bearing tetradentate bis(aminophenoxide) ligands is reported and shown to initiate the living ring-opening polymerization of rac-lactide. The microstructures of the polylactide products are found to be highly dependent upon the ancillary ligand substituents, ranging from highly isotactic (Pm = 0.79) to very highly heterotactic (Pr = 0.96).

Stereoselective ring-opening polymerization ofrac-lactide with a single-site, racemic aluminum alkoxide catalyst: Synthesis of stereoblock poly(lactic acid)

The polymerization of racemic lactide with a racemic aluminum alkoxide catalyst is reported. Microstructural analysis of the polymer produced with 1 H NMR spectroscopy revealed that an isotactic stereoblock poly(lactic acid) formed, where each enantiomerically pure block contained an average of 11 lactide monomer units. The melting point of this polymer, 179°C, was higher than that of the enantiomerically pure polymer, consistent with the cocrystallization of the enantiomeric blocks of the polymer. The mechanism of the polymer formation is currently unknown, although a polymer exchange pathway, where living chain ends switch between metal centers to produce diastereomeric active species, is proposed.