Ring-opening Polymerization Of Racemic Lactide Research Articles

Influence of monomer purity on molecular weight of racemic polylactic acid

Aiming at the low molecular weight of polylactic acid due to the presence of water molecules in the ring-opening polymerization of racemic lactide, this paper selected racemic lactide as the main raw material, stannous caprylate as the catalyst, and cetyl alcohol as the initiator, and studied the effects of recrystallization process conditions such as the number of recrystallization and drying time on the purity of monomer. The influence of initiator dosage on the properties of racemic polylactic acid was also studied. The purity, water content and free acid content of racemic lactide were determined by infrared spectrometer, differential scanning calorimeter, Gel Permeation Chromatography and tensile testing machine. The molecular weight and mechanical properties of racemic polylactic acid were characterized. The results show that the purity of racemic lactide after recrystallization can reach 99.3%, the water content is as low as 0.008% and the free acid content is less than 0.1%. When the amount of initiator is 0.13%, the molecular weight of the prepared racemic polylactic acid is 14.06 KDa and the tensile strength is 37 MPa.

Bayesian-optimization-assisted discovery of stereoselective aluminum complexes for ring-opening polymerization of racemic lactide

Stereoselective ring-opening polymerization catalysts are used to produce degradable stereoregular poly(lactic acids) with thermal and mechanical properties that are superior to those of atactic polymers. However, the process of discovering highly stereoselective catalysts is still largely empirical. We aim to develop an integrated computational and experimental framework for efficient, predictive catalyst selection and optimization. As a proof of principle, we have developed a Bayesian optimization workflow on a subset of literature results for stereoselective lactide ring-opening polymerization, and using the algorithm, we identify multiple new Al complexes that catalyze either isoselective or heteroselective polymerization. In addition, feature attribution analysis uncovers mechanistically meaningful ligand descriptors, such as percent buried volume (%Vbur) and the highest occupied molecular orbital energy (EHOMO), that can access quantitative and predictive models for catalyst development.

Structural Effect of Organic Catalytic Pairs Based on Chiral Amino(thio)ureas and Phosphazene Bases for the Isoselective Ring-Opening Polymerization of Racemic Lactide

Structural Effect of Organic Catalytic Pairs Based on Chiral Amino(thio)ureas and Phosphazene Bases for the Isoselective Ring-Opening Polymerization of Racemic Lactide

Highly Active Organocatalysts for Stereoselective Ring-Opening Polymerization of Racemic Lactide at Room Temperature.

Although significant advances have been achieved, highly stereocontrolled polymerization using organocatalysts is still a great challenge, such as ring-opening polymerization of racemic lactide (rac-LA) for the synthesis of stereoregular polylactide (PLA). In this context, a series of binary organocatalysts consisting of different phosphazenes (CTPB, C3N3-Me-P3, C3N3-Py-P3, t-BuP2, and t-BuP4) and achiral ureas (U1-U6) were applied for the stereocontrolled ROP of rac-LA under mild conditions. It is remarkable that C3N3-Py-P3/U4 with the compatible basicity/acidity showed both high activity (92% conversion within 10 min) and great stereoselectivity (Pm = 0.92) at room temperature (20 °C), and the resultant stereoblock PLA had predictable molar mass, narrow distribution (Đ = 1.07), and high melting temperature (Tm = 190 °C). Interactions involved among phosphazene, urea, and initiator were investigated by an in situ NMR technique. It was found that C3N3-Py-P3 reacted with benzyl alcohol (BnOH) to form a relatively loose ion pair in the presence of U4, which accounted for both high activity and stereoselectivity. Kinetics studies for different LA monomers at 20 °C showed kobs-1 (rac-LA) = 0.212 min-1, kobs-1 (D-LA) = 0.311 min-1, and kobs-1 (L-LA) = 0.317 min-1, indicative of the chain end control mechanism for stereocontrolled ROP.

Reaching High Stereoselectivity and Activity in Organocatalyzed Ring-Opening Polymerization of Racemic Lactide by the Combined Use of a Chiral (Thio)Urea and a N-Heterocyclic Carbene.

Stereochemical control during polymerization is a key strategy of polymer chemistry to achieve semicrystalline engineered plastics. The stereoselective ring-opening polymerization (ROP) of racemic lactide (rac-LA), which can lead to highly isotactic polylactide (PLA), is one of the emblematic examples in this area. Surprisingly, stereoselective ROP of rac-LA employing chiral organocatalysts has been under-leveraged. Here we show that a commercially available chiral thiourea (TU1), or its urea homologue (U1), can be used in conjunction with an appropriately selected N-heterocyclic carbene (NHC) to trigger the stereoselective ROP of rac-LA at room temperature in toluene. Both a high organic catalysis activity (>90% monomer conversion in 5-9 h) and a high stereoselectivity (probability of formation of meso dyads, Pm, in the range 0.82-0.93) can be achieved by thus pairing a NHC and a chiral amino(thio)urea. The less sterically hindered and the more basic NHC, that is, a NHC bearing tert-butyl substituents (NHCtBu), provides the highest stereoselectivity when employed in conjunction with the chiral TU1 or U1. This asymmetric organic catalysis strategy, as applied here in polymerization chemistry, further expands the field of possibilities to achieve bioplastics with adapted thermomechanical properties.

Isoselective Ring-opening Polymerization of Racemic Lactide Catalyzed by N-heterocyclic Olefin/(Thio)urea Organocatalysts

The isoselective ring-opening polymerization of racemic lactide was achieved by combining N-heterocyclic olefin (NHO) with mono(thio)ureas or bis(thio)ureas as catalytic systems. The polymerization process shows high stereoselectivity, controllability and reactivity, delivering multi-block isotactic polylactides with high chain-end fidelity and narrow molecular weight distributions. The enhancement of catalytic performance was observed in the following order: bisthiourea (DTU) < monothiourea (TU) < bisurea (DU) < urea (U). The highest Pm (probability of forming a meso dyad) = 0.91 was observed at −70 °C when using NHO/U1 catalytic system and the high stereoselectivity was attributed to chain-end control mechanism.

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.

Highly active rare-earth metal catalysts for heteroselective ring-opening polymerization of racemic lactide

Rare-earth metal complexes usually exhibit high activities in the ring-opening polymerization (ROP) of lactide, yet only a few scandium complexes have shown satisfactory activity. Herein, we report the synthesis of a series of chiral anilido-oxazoline-supported scandium and yttrium complexes that exhibit high activity in the ROP of racemic lactide (rac-LA). Complexes La-f-Ln(CH2SiMe3)2THF (La-f = 2-(2,6-R2PhN)-phenyl-4-(S)-R'-oxazoline; for 1a-f: L = La-f, Ln = Sc; for 2a-d: L = La-d, Ln = Y) were synthesized via the convenient one-pot reaction of Ln(CH2SiMe3)3(THF)2 (Ln = Sc, Y) with the corresponding proligands. The crystal structures of 1a, 1d, 1e, and 1f were isostructural, adopting a distorted trigonal bipyramidal configuration. Sc complexes 1 showed outstanding activity in the ROP of rac-LA with heteroselectivity. TOFs of up to 720 h-1 and 2910 h-1 were obtained in THF at room temperature and toluene at 60 °C, respectively. To our knowledge, these are the highest activities reported for Sc systems. Y complexes 2 showed higher activity and heteroselectivity than the Sc complexes, with TOFs of up to 1176 h-1 in THF at room temperature. Compared with the ortho-substituent on the anilido moiety, the bulky substituent at the chiral center of the oxazoline ring had a greater effect on controlling the heteroselectivity.

Stereoselective photoredox ring-opening polymerization of O-carboxyanhydrides

Biodegradable polyesters with various tacticities have been synthesized by means of stereoselective ring-opening polymerization of racemic lactide and β-lactones but with limited side-chain groups. However, stereoselective synthesis of functional polyesters remains challenging from O-carboxyanhydrides that have abundant pendant side-chain functional groups. Herein we report a powerful strategy to synthesize stereoblock polyesters by stereoselective ring-opening polymerization of racemic O-carboxyanhydrides with the use of photoredox Ni/Ir catalysts and a selected Zn complex with an achiral ligand. The obtained stereoblock copolymers are highly isotactic with high molecular weights ( > 70 kDa) and narrow molecular weight distributions (Mw/Mn < 1.1), and they display distinct melting temperatures that are similar to their stereocomplex counterparts. Furthermore, in one-pot photoredox copolymerization of two different O-carboxyanhydrides, the use of such Zn complex mediates kinetic resolution of the comonomers during enchainment and shows a chirality preference that allows for the synthesis of gradient copolymers.

Scandium and yttrium complexes of an hybrid phenoxy-amidopyridinate ligand. Use in ROP of racemic lactide

The new multidentate hybrid phenol-aminopyridine proligand {NMe2NNMe2CiPr2O}H2 (1-H2) was prepared and used in σ-bond metathesis reactions with the trialkyl precursors M(CH2SiMe3)3(THF)2 (M = Sc, Y). These reactions afforded cleanly the corresponding alkyl complexes {NMe2NNMe2CiPr2O}M(CH2SiMe3)(THF) (M = Sc (1-Sc), Y (1-Y)), which were characterized by NMR spectroscopy and microanalysis. Upon crystallization, 1-Sc disproportionates to form the bis(ligand) complex 2-Sc which was isolated and characterized by X-ray crystallography. Complexes 1-Sc and 1-Y were used as initiators in the ring-opening polymerization (ROP) of racemic lactide, alone or in combination with iPrOH, to give atactic PLAs with controlled molecular weights.

The Role of Nitrogen Donors in Zinc Catalysts for Lactide Ring-Opening Polymerization.

The electronic effects of nitrogen donors in zinc catalysts for ring-opening polymerization of cyclic esters were investigated. Alkyl and benzyloxy zinc complexes supported by tridentate diamino- and aminoimino phenolate ligands were synthesized, and their solid-state and solution structures characterized. The solution-state structures showed that the alkyl complexes are mononuclear, while the alkoxy complexes are dimeric with the ligands coordinated with different denticities depending on the nature of the ligand donors. The catalytic activities of these compounds toward the ring-opening polymerization of racemic lactide were studied and showed that catalysts with secondary and imine nitrogen donors are more active than analogues with tertiary amines.

Dinucleating Ligand Platforms Supporting Indium and Zinc Catalysts for Cyclic Ester Polymerization.

The synthesis of the first alkoxide-bridged indium complex supported by a chiral dinucleating ligand platform (1), along with its zinc analogue (2), is reported. Both complexes are synthesized in a one-pot reaction starting from a chiral dinucleating bis(diamino)phenolate ligand platform, sodium ethoxide, and respective metal salts. The dinucleating indium analogue (7) based on an achiral ligand backbone is also reported. Indium complexes bearing either the chiral or achiral ligand catalyze the ring-opening polymerization of racemic lactide (rac-LA) to afford highly heterotactic poly(lactic acid) (PLA; Pr > 0.85). The indium complex bearing an achiral ligand affords essentially atactic PLA from meso-LA. The role of the dinucleating ligand structure in catalyst synthesis and polymerization activity is discussed.

Zinc, aluminum and group 3 metal complexes of sterically demanding naphthoxy-pyridine ligands: Synthesis, structure, and use in ROP of racemic lactide and β-butyrolactone

New potentially tridentate, bulky ortho-Ph3Si-substituted naphthol-pyridine proligands a–f were synthesized and introduced onto zinc, aluminum and group 3 metal centers (M=Sc, Y, La) using straightforward one-step alkane or amine elimination protocols. The solid-state structures of these mononuclear zinc (1a, 1c, 1d, 2c and 2e) and aluminum (3c) complexes were determined by single-crystal X-ray diffraction studies, while the solution structures were established using 1H, 13C{1H} and 29Si/29Si{1H} (when appropriate) NMR spectroscopy. For all complexes, only one species (isomer) of C1 symmetry was observed by NMR spectroscopy in the broad temperature range. Most of these complexes are effective initiators for the ring-opening polymerization (ROP) of racemic lactide (rac-LA) at 25–100°C, affording poly(lactides)s (PLAs) generally with unimodal dispersities and molecular weights in good agreement with calculated values. An yttrium complex (4e) proved the most active (TOF=1840mol(LA)mol(Y)−1h−1 at 25°C) and yielded heterotactic-enriched PLAs (Pr up to 0.80) in toluene, while atactic PHBs were formed in the ROP of racemic β-butyrolactone (rac-BBL) under the same conditions.

Scandium versus yttrium{amino-alkoxy-bis(phenolate)} complexes for the stereoselective ring-opening polymerization of racemic lactide and β-butyrolactone.

Scandium and yttrium amide complexes Ln{ONXO(R1,R2)}(N(SiHMe2)2)(THF)n (Ln = Sc, n = 0 or Y, n = 1; X = NMe2 or OMe; R(1) = Cumyl or p-Cl-Cumyl; R(2) = Me or Cumyl) were prepared by aminolysis of Ln[N(SiHMe2)2]3(THF) with the corresponding tetradentate diamino- or alkoxy-amino-bis(phenol) pro-ligands {ONXO(R1,R2)}H2. In the solid state and in toluene solution, the scandium complexes are monomeric and 5-coordinated, while the analogous yttrium complexes all bear an extra THF-coordinated molecule and are 6-coordinated. Sc{ONXO(R1,R2)}(N(SiHMe2)2) complexes are single-site initiators for the ring-opening polymerization (ROP) of racemic lactide but are less active than their yttrium analogues Y{ONXO(R1,R2)}(N(SiHMe2)2)(THF); also, in contrast to the latter ones, they are inactive in the ROP of the more demanding racemic β-butyrolactone. On the other hand, the scandium amide complexes feature a significantly improved control over the ROP of lactide, yielding PLAs with much narrower molecular weight distributions (Đ(M) < 1.1 for Sc vs. 1.5-2.0 for Y). The yttrium complex with the very bulky o,p-dicumyl-substituted ligand is more heteroselective than its scandium analogue (P(r) = 0.88 vs. 0.83), while the opposite is observed with complexes based on p-methyl-substituted ligands (P(r) = 0.50 in toluene or 0.72-0.75 in THF for Y vs. P(r) = 0.75-0.83 for Sc in toluene). These reactivity and selectivity trends are rationalized by a much more sterically crowded coordination sphere in scandium than in yttrium complexes.

Yttrium– and Aluminum–Bis(phenolate)pyridine Complexes: Catalysts and Model Compounds of the Intermediates for the Stereoselective Ring-Opening Polymerization of Racemic Lactide and β-Butyrolactone

Yttrium and aluminum complexes of an original pyridine-bis(phenolate) ligand have been prepared. Reactions of {ONOMe,Cumyl}Y[N(SiHMe2)2](THF)(Et2O) (1) with 1 equiv of methyl (R)-3-hydroxybutyrate and methyl (S,S)-lactyllactate afforded respectively {ONOMe,Cumyl}Y((R)-OCH(CH3)CH2COOMe) (2) and {ONOMe,Cumyl}Y((S,S)-OCH(CH3)CO2CH(CH3)CO2Me) (3), which are rare models of the active species in the ring-opening polymerization (ROP) of β-butyrolactone (BBL) and lactide (LA), respectively. 13C NMR data for 2 and 3 indicate that, in solution, the carbonyl groups coordinate onto the yttrium centers, forming mononuclear species with six- and five-membered cycles, respectively. The aluminum compounds {ONOMe,Cumyl}Al(iPr (S)-lactate) (5), {ONOMe,Cumyl}Al((R)-OCH(CH3)CH2COOCH3) (6), and {ONOMe,Cumyl}Al((rac)-OCH(CF3)CH2CO2C2H5) (7) were prepared analogously from the parent methyl complex {ONOMe,Cumyl}AlMe (4). NMR data and the solid-state structure of 6 confirm the coordination of the carbonyl group. Yttrium compounds 1 and 2 are active initiators for the ROP of racemic LA and BBL. Their performances (activity, control of the molecular weights, tacticity) are much affected by the nature of the solvent or by the addition of just a few equivalents of pyridine. Optimal conditions are quite contrasted for the ROP of rac-LA and rac-BBL, highlighting fundamental differences between these two monomers. In the best cases, highly heterotactic PLAs (Pr up to 0.96) and syndiotactic-enriched PHB (Pr up to 0.86), with good control over the molecular weights, were obtained.

Effects of ligand tuning on dinuclear indium catalysts for lactide polymerization

Functionalized diaminophenols, H(N(R1R2)N(R3)O), were investigated as ligands for indium catalysts in the ring-opening polymerization of racemic lactide. Precursor complexes (N(Me2)N(Me)O)InCl(2) (1), (N(Pr2)NO)InCl(2) (2), and (N(Mes)NO)InCl(2) (3) were synthesized and fully characterized by (1)H and (13)C NMR spectroscopy, elemental analysis, and single-crystal X-ray crystallography. Complexes 1 and 2 were used to synthesize alkoxy-bridged complexes [(N(Me2)N(Me)O)InCl](2)(μ-Cl)(μ-OEt) (4) and [(N(Pr2)NO)InCl](2)(μ-Cl)(μ-OEt) (5). These complexes catalysed the polymerization of racemic lactide at different rates, with complex 5 being substantially more active than complex 4. The dissociation behaviour of these catalysts in the presence of lactide was also studied and used to make comparisons with previously reported catalyst systems.

Highly heteroselective ring-opening polymerization of racemic lactide initiated by divalent ytterbium complexes bearing amino bis(phenolate) ligands

Polymerization of racemic lactide initiated by divalent ytterbium complexes supported by either dimethylamino-amino bis(phenolate) or methoxy-amino bis(phenolate) ligands proceeds rapidly at room temperature in a living fashion to give heterotactic polylactide with the racemic enchainment of monomer units P(r) ranging from 0.97-0.99.

Random Copolymerization of ε-Caprolactone with Lactide Using a Homosalen−Al Complex

The bulky substituents of homosalen complexes decelerate the ring-opening polymerization of racemic lactide (LA). The substituent effects provide the first catalysis for the random copolymerization of epsilon-caprolactone (CL) with LA (CL/LA = 1:1). The copolymerization of CL with LA (CL/LA = 1:1) by the iPr(3)Si-substituted homosalen-Al complex 2 affords the practically random copolymer in a controlled manner. The reactivity ratios, average sequence lengths of CL and LA during the copolymerization, abundance ratios of the triad caproyl sequences, and T(g) value of the obtained copolymer indicate that the copolymer was random with a somewhat alternative tendency (r(CL)r(LA) = 0.80).

Group 3 metal complexes supported by tridentate pyridine- and thiophene-linked bis(naphtholate) ligands: synthesis, structure, and use in stereoselective ring-opening polymerization of racemic lactide and β-butyrolactone

Scandium, yttrium and lanthanum amido complexes supported by tridentate bis(ortho-silyl-substituted naphtholate)-donor ligands ({ONO(SiPh3)}(2-) and {ONO(SitBuMe2)}(2-), donor = 2,6-pyridine; {OSO(SiPh3)}(2-), donor = 2,5-thiophene) have been prepared in high yields (72-96%) by reaction of the corresponding pro-ligand {OZO(SiR3)}H(2) and Ln[N(SiHMe(2))(2)](3)(THF)(n) precursor. The solid-state structures of {ONO(SiPh3)}La[N(SiHMe(2))(2)](THF) (3), {ONO(SitBuMe2)}Ln[N(SiHMe(2))(2)](THF) (Ln = Sc, 4; Y, 5) and {OSO(SiPh3)}Ln[N(SiHMe(2))(2)](THF) (Ln = Sc, 7; La, 9) have been determined by single-crystal X-ray diffraction studies. In all five complexes, the naphtholate rings twist in the same direction from the plane of the pyridine or thiophene linker, to give rise to C(s)-symmetric (non crystallographic) structures. Compounds are 1-9 single-site initiators for the ring-opening polymerization (ROP) of racemic lactide (rac-LA) at 20 degrees C, affording poly(lactides)s (PLAs) with relatively narrow polydispersities and molecular weights in good agreement with calculated values. When carried out in THF, the polymerizations afforded heterotactic-enriched PLAs (P(r) up to 0.93), while atactic polymers are formed in toluene. Compounds 1-3 and 7-9, having o-SiPh(3) substituents on the naphtholate rings, are also active for the ROP of racemic beta-butyrolactone at 20-50 degrees C, to form syndiotactic-enriched poly(3-hydroxybutyrate)s (PHBs) (P(r) up to 0.87) when using toluene as the solvent, whereas atactic polymers were obtained in THF. The nature of the metal center (Sc, Y, La), the central linker in the ligand framework (pyridine, thiophene), and the ortho-silyl substituent (SiPh(3), SiMe(2)tBu) significantly affect the degree of stereocontrol in those polymerizations.

Aluminum Complexes of Fluorinated β-Diketonate Ligands: Syntheses, Structures, Intramolecular Reduction, and Use in Ring-Opening Polymerization of Lactide

Routes toward heteroleptic Al complexes supported by fluorinated β-diketonate ligands have been studied. Reactions of pro-ligands (acacR1,R2)H (R1 = R2 = CF3, “(hfacac)H”; R1 = CF3, R2 = tBu) with 0.5 equiv of AlMe3 or AlMe2Cl systematically yielded the corresponding homoleptic complexes Al(hfacac)3 (1) and Al(acacCF3,tBu)3 (2). Compound 2 exists in CD2Cl2 solution as a mixture of fac- and mer-isomers. Heteroleptic complexes [Al(acacR1,R2)2(OiPr)]n (R1 = R2 = CF3, 3; R1 = CF3, R2 = tBu, 4) were cleanly prepared from the reaction of the corresponding (acacR1,R2)H pro-ligands and 0.5 equiv of AlMe2(OiPr). Reaction of (hfacac)H and 0.5 equiv of Al(OiPr)3 at room temperature afforded 3 contaminated by other products, of which [κ2:μ2-(hfacac)5(OiPr)4Al3] (5) was isolated. When the same reaction was carried out at 55 °C, (S,R)-[κ,μ:κ2-(4H-hfacac)(hfacac)Al(THF)]2 (6), which contains a μ-bridging dianionic ligand (4H-hfacac)2− that arises from the reduction of one carbonyl group in (hfacac)−, was isolated in moderate yield (22%). Single-crystal X-ray diffraction studies revealed that complexes 3, 6, and 7 ([Al(hfacac)2(OH)]2, the hydrolysis product of 3) are dinuclear in the solid state with μ-bridging isopropoxide or hydroxide groups, while 5 features a symmetric trinuclear structure with the two terminal Al atoms supported by two (hfacac)− ligands and bridged via μ-isopropoxide groups to a central Al atom supported by a single (hfacac)− ligand. The Al-OiPr complexes 3 and 4 are effective initiators for the ring-opening polymerization of racemic lactide in THF or toluene solutions, giving atactic PLAs, end-capped by OiPr and OH groups, with controlled molecular weights (Mn up to 30 300 g·mol−1) and relatively narrow polydispersities (Mw/Mn = 1.10−1.32).