WO2015113168A1

WO2015113168A1 - Crystalline poly(lactic acid) and process for production thereof

Info

Publication number: WO2015113168A1
Application number: PCT/CA2015/050078
Authority: WO
Inventors: Timothy James Clark; Rina Carlini; Yun Yang; Craig Andrew WHEATON; Paul David THORNTON
Original assignee: Greencentre Canada
Priority date: 2014-02-03
Filing date: 2015-02-03
Publication date: 2015-08-06

Abstract

This application relates to a melt polymerization process for ring-opening polymerization of cyclic monomers. The process is useful for production of crystalline poly(lactic acid). More specifically, the application provides a poly(lactic acid) having a crystallinity of ≥80% and a T_m≥170˚C, and a process for production thereof. The process comprises a ring-opening, melt polymerization of cyclic monomers, such as lactides, in the presence of an salen indium catalyst.

Description

CRYSTALLINE POLY(LACTIC ACID) AND PROCESS FOR PRODUCTION THEREOF

FIELD OF THE INVENTION

[0001 ] The application pertains to the field of ring-opening polymerization processes. More particularly, the application relates to a ring-opening melt polymerization process for production of polymers having a high crystallinity, a high T_m and/or a high molecular weight.

INTRODUCTION

[0002] Global demand for biodegradable polymers is growing rapidly to address the need for compostable and recyclable plastic products. Poly(Lactic Acid), or PLA, represents the largest segment of these biodegradable polymers, and annual sales of PLA are expected to surpass $3 billion by 2016.

Poly(lactic acid)

PLA

[0003] Several grades of PLA are currently produced with a range of physical and performance properties that enable its use in disposable and biodegradable plastic items, such as food service ware, non-wovens and rigid packaging. However, there is growing demand for high- performance PLA, having higher melting temperatures and crystallinity, to allow its use in mechanically durable and heat-resistant plastic products.

[0004] PLA can be produced via ring opening polymerization (ROP) of six-membered cyclic ester lactides (Dechy-Cabaret, O.; Martin-Vaca, B.; Bourissou, D. Chem. Rev. 2004, 104, 6147- 6176.; Gupta, B.; Revagade, N.; Hilborn, J. Prog. Poly. Sci. 2007, 32, 455-482.; Oh, J. K. Soft Matter 201 1 , 7, 5096-5108.). Lactic acid (LA) can be produced in chiral and racemic forms by fermentation of corn and other agricultural products. Lactides are cyclic diesters of lactic acid, and are prepared via dehydration of lactic acid. When a lactide is prepared from racemic lactic acid, three isomers result: R-lactide (D-lactide), S-lactide (L-lactide) and meso-lactide. rac- lactide is a 50:50 mixture of R-lactide and S-lactide.

R-lactide S-lactide meso-lactide

[0005] Stereochemistry of PLAs determines, at least in part, their mechanical, physical and thermal properties, as well as their rates of degradation. Bulk properties of PLAs, especially their melting points, are intrinsically linked to polymer microstructure. Poly(R-lactic acid) and poly(S- lactic acid) are both crystalline polymers with melting points of about 180°C, while atactic PLA, produced from polymerization of RS-lactide, is an amorphous polymer with no melting point. Controlling a polymer's tacticity can have an enormous impact on its final properties and applications (Dijkstra, P. J.; Du, H. Z.; Feijen, J. Polym. Chem. 201 1 , 2, 520-527; Buffet, J. C ; Okuda, J. Polym. Chem. 201 1 , 2, 2758-2763; Thomas, C. M. Chem. Soc. Rev. 2010, 39, 165- 173; Stanford, M. J.; Dove, A. P. Chem. Soc. Rev. 2010, 39, 486-494.)

[0006] Isotactic PLA derived solely from L-lactide (P_m≥ 0.8, where P_m is probability of finding a pair of adjacent structural units that have equivalent stereochemistries) has a melting point of 178 °C, while all heterotactic polymers generated to date through chain end control are amorphous (Buffet, J. C; Okuda, J. Polym. Chem. 201 1 , 2, 2758-2763; Fukushima, K.; Kimura, Y. Polym. Int. 2006, 55, 626-642).

[0007] Stereoselective complexes for use in ROP of rac-lactide are rare. Site selective systems are generally limited to chiral aluminum complexes for LA ROP, as reported by Spassky (Spassky, N.; Wisniewski, M.; Pluta, C; LeBorgne, A. Macromol. Chem. Phys. 1996, 197, 2627- 2637) Coates (Ovitt, T. M.; Coates, G. W. J. Am. Chem. Soc. 1999, 121, 4072-4073; Ovitt, T. M.; Coates, G. W. J. Polym. Sci. Pol. Chem. 2000, 38, 4686-4692; Ovitt, T. M.; Coates, G. W. J. Am. Chem. Soc. 2002, 124, 1316-1326), Smith, (Radano, C. P.; Baker, G. L; Smith, M. R. J. Am. Chem. Soc. 2000, 122, 1552-1553) and Feijen (P_m > 0.9) (Zhong, Z. Y. ; Dijkstra, P. J.; Feijen, J. Angew. Chem. Int. Ed. 2002, 41, 4510-4513; Zhong, Z. Y.; Dijkstra, P. J.; Feijen, J. J. Am. Chem. Soc. 2003, 125, 1 1291 -1 1298). [0008] Chiral catalysts can be used to selectively polymerize one stereoisomer in a racemic mixture of lactides to produce isotactically enriched PLA. For example, metal-salen complexes have been widely used in asymmetric catalysis including stereoselective polymerization of rac- lactide (Canali, L; Sherrington, D.C. Chem. Soc. Rev. 1999, 28, 85; Dechy-Cabaret, O.; Martin- Vaca, B.; Bourissou, D. Chem. Rev. 2004, 104, 6147.). Salen-aluminum complexes in particular have been found to have utility for stereoselectively catalyzing syntheses of PLA (Ovitt, T. M.; Coates, G. W. J. Am. Chem. Soc. 2002, 124, 1316; Zhong, Z.; Dijkstra, P. J.; Feijen, J. Angew. Chem. Int. Ed. 2002, 41, 4510.). However, while site selective chiral aluminum complexes can successfully generate isotactic PLA, they suffer from low reactivity and often require several hours, or days, at elevated temperatures to achieve high conversions (Zhong, Z.; Dijkstra, P. J.; Feijen, J. Angew. Chem. Int. Ed. 2002, 41, 4510; Nomura, N. et al., Chem. Eur. J. 2007, 13, 4433 - 4451).

[0009] Recently, salen indium catalysts, having the general structure shown below (see paragraph [0012]), were developed and found to be useful in catalyzing ring opening polymerizations, such as the polymerization of lactide (International PCT Application No.

PCT/CA2013/050191 , which is expressly incorporated herein in its entirety). These indium complexes, bearing a salen ligand(s), have been shown to provide a combination of site- selectivity and activity for the ring opening polymerization of lactide. However, to date, these complexes have not been successfully used to synthesize PLA via a ring-opening melt polymerization to afford an end polymer with high crystallinity, melt temperatures, and/or high molecular weights.

[0010] The above information is provided for the purpose of making known information believed by the applicant to be of possible relevance to the present application. No admission is necessarily intended, nor should be construed, that any of the preceding information constitutes prior art against the invention, as described herein.

SUMMARY OF THE INVENTION

[001 1 ] In accordance with an aspect of the application there is provided a poly(lactic acid) (PLA) polymer of formula (I)

(1)

wherein the PLA has a crystallinity of >80% and a T_m >170°C.

[0012] In one embodiment, the PLA of formula (1) is prepared by ring-opening polymerization, comprising: reacting R-lactide of formula (2a), S-lactide of formula (2b), and/or rac-lactide of formula (2c),

(2a) (2b) (2c), in the presence of a catalyst of formula (3a) and/or (3b)

wherein the dashed line represents an optional double bond; each R1 is an optionally substituted C2-5 alkylene,

each R² is independently hydrogen, halogen, optionally substituted linear or branched CMS alkyl (e.g., C1-10 alkyl), optionally substituted cyclic C3-18 alkyl (e.g., cyclic C3-12 alkyl), or optionally substituted phenyl or SiR', where R' is alkyl or aryl; each R³ is hydrogen, optionally substituted linear or branched CMS alkyl (e.g., Ci- 10 alkyl), or optionally substituted cyclic C3-18 alkyl (e.g., cyclic C3-12 alkyl); each R is independently OR⁴, NR⁴ ₂, SR⁴, or CH₂SiR⁴ ₃, where R⁴ is hydrogen, optionally substituted linear or branched CMS alkyl (e.g., C1-5 alkyl), such as a fluoro-substituted alkyl, or optionally substituted linear or branched (C1-12) alkylcarbonyl (e.g., (Ci-5)alkylcarbonyl), such as C(0)CH20CH3; and each R⁵ is independently hydrogen, optionally substituted linear or branched CMS alkyl (e.g., C1-10 alkyl), optionally substituted cyclic C3-18 alkyl (e.g., cyclic C3-12 alkyl) or, when there is a C-N double bond, absent; until polymerization is deemed complete, to form the PLA of formula (I)

[0013] In another embodiment, the PLA of formula (I) is prepared by a melt, ring-opening polymerization.

[0014] In accordance with another aspect, there is provided a process for producing PLA by ring- opening polymerization, comprising: reacting D-lactide of formula (2a), L-lactide of formula (2b), and/or rac-lactice of formula (2c),

(2a) (2b) (2c), in the presence of a catalyst of formula (3a) and/or (3b)

wherein

the dashed line represents an optional double bond; each R1 is an optionally substituted C2-5 alkyl

each R² is independently hydrogen, halogen, optionally substituted linear or branched CMS alkyl (e.g., C1-10 alkyl), optionally substituted cyclic C3-18 alkyl (e.g., cyclic C3-12 alkyl), or optionally substituted phenyl or SiR', where R' is alkyl or aryl; each R³ is hydrogen, optionally substituted linear or branched CMS alkyl (e.g., Ci- 10 alkyl), or optionally substituted cyclic C3-18 alkyl (e.g., cyclic C3-12 alkyl); each R is independently OR⁴, NR⁴ ₂, SR⁴, or CH₂SiR⁴ ₃, where R⁴ is hydrogen, optionally substituted linear or branched CMS alkyl (e.g., C1-5 alkyl), such as a fluoro-substituted alkyl, or optionally substituted linear or branched (C1-12) alkylcarbonyl (e.g., (Ci-5)alkylcarbonyl), such as C(0)CH₂0CH3; and each R⁵ is independently hydrogen, optionally substituted linear or branched CMS alkyl (e.g., C1-10 alkyl), optionally substituted cyclic C3-18 alkyl (e.g., cyclic C3-12 alkyl) or, when there is a C-N double bond, absent;

until polymerization is deemed complete, to form the PLA of formula (I)

(1 ),

wherein, the PLA of formula (I) has a crystallinity of >80% and a T_m >170°C. [0015] In one embodiment, the process further comprises reacting the D-lactide of formula (2a), L-lactide of formula (2b), and/or rac-lactide of formula (2c) with the catalyst of formula (3a) and/or (3b), in the presence of a chain transfer agent (CTA). In another embodiment, the chain transfer agent is benzyl alcohol, ethanol, isopropanol, or tert-butanol. In yet another embodiment, the ratio of lactide:catalyst:CTA is 1000:1 :5; or, 1000:1 :0; or, 5000:1 :5; or, 5000:1 :0; or, 10 000:1 :5; or, 10 000: 1 :0; or, 15 000:1 :5; or, 15 000: 1 :0; or, 20 000:1 :5; or, 20 000:1 :0.

[0016] In one embodiment, the ring-opening polymerization a melt polymerization. In another embodiment, the melt polymerization occurs at <180°C; or, <160°C; or, <140°C; or, >120°C.

[0017] In one embodiment, the lactide of the process comprises <10% D-lactide of formula (2a), and >90% L-lactide of formula (2b); or, <8% D-lactide of formula (2a), and >92% L-lactide of formula (2b); or, 6% D-lactide of formula (2a), and >94% L-lactide of formula (2b); or, <4% D- lactide of formula (2a), and >96% L-lactide of formula (2b); or, <2% D-lactide of formula (2a), and >98% L-lactide of formula (2b). In another embodiment, the D-lactide of formula (2a), L-lactide of formula (2b), and/or rac-lactice of formula (2c) is recrystallized prior to polymerization to form the PLA of formula (I).

[0018] In accordance with another aspect, there this provided a process for producing PLA by ring-opening polymerization, comprising:

(i) dissolving a catalyst of formula (3a) and/or (3b) in a solvent,

each R² is independently hydrogen, halogen, optionally substituted linear or branched CMS alkyi (e.g., C1-10 alkyi), optionally substituted cyclic C3-18 alkyi (e.g., cyclic C3-12 alkyi), or optionally substituted phenyl or SiR', where R' is alkyi or aryl; each R³ is hydrogen, optionally substituted linear or branched CMS alkyl (e.g., Ci- 10 alkyl), or optionally substituted cyclic C3-18 alkyl (e.g., cyclic C3-12 alkyl); each R is independently OR⁴, NR⁴ ₂, SR⁴, or CH₂SiR⁴ ₃, where R⁴ is hydrogen, optionally substituted linear or branched CMS alkyl (e.g., C1-5 alkyl), such as a fluoro-substituted alkyl, or optionally substituted linear or branched (C1-12) alkylcarbonyl (e.g., (Ci-5)alkylcarbonyl), such as C(0)CH20CH3; and each R⁵ is independently hydrogen, optionally substituted linear or branched CMS alkyl (e.g., C1-10 alkyl), optionally substituted cyclic C3-18 alkyl (e.g., cyclic C3-12 alkyl) or, when there is a C-N double bond, absent;

(ii) melting D-lactide of formula (2a), L-lactide of formula (2b), and/or rac-lactice of formula (2c)

(iii) adding the dissolved catalyst to the melted D-lactide of formula (2a), L-lactide of formula (2b), and/or rac-lactice of formula (2c); and

(iv) reacting the D-lactide of formula (2a), L-lactide of formula (2b), and/or rac- lactice of formula (2c) in the presences of the catalyst of formula (3a) and/or (3b) until polymerization is deemed complete, to form the PLA of formula (I)

wherein the PLA of formula (I) has (a) a M_w≥160 000, and (b) a crystallinity of >80% and/or a T_m >170°C. [0019] In one embodiment, the solvent used in the process is an anhydrous, non-Lewis basic solvent. In another embodiment, the solvent is toluene; or isopropyl acetate; or, tert-butyl acetate; or, methyl tert-butyl ether' or, xylenes; or, cymene; or, a chlorinated solvent; or, a bulky ester solvent; or, a bulky ether solvent; or, an aromatic solvent.

[0020] In one embodiment, the process further comprises addition of a chain transfer agent (CTA). In another embodiment, the CTA is added to the D-lactide of formula (2a), L-lactide of formula (2b), and/or rac-lactide of formula (2c), prior to the addition the catalyst of formula (3a) and/or (3b). In another embodiment, the chain transfer agent is benzyl alcohol, ethanol, isopropanol, or tert-butanol. In yet another embodiment, the lactide:catalyst:CTA is 1000:1 :5; or, 1000:1 :0; or, 5000:1 :5; or, 5000:1 :0; or, 10 000:1 :5; or, 10 000: 1 :0; or, 15 000:1 :5; or, 15 000:1 :0; or, 20 000: 1 :5; or, 20 000:1 :0.

[0021 ] In one embodiment, the ring-opening polymerization is a melt polymerization. In another embodiment, the melt polymerization occurs at <180°C; or, <160°C; or, <140°C; or >120°C.

[0022] In one embodiment, the lactide of said process comprises <10% D-lactide of formula (2a), and >90% L-lactide of formula (2b); or, <8% D-lactide of formula (2a), and >92% L-lactide of formula (2b); or, 6% D-lactide of formula (2a), and >94% L-lactide of formula (2b); or, <4% D- lactide of formula (2a), and >96% L-lactide of formula (2b); or, <2% D-lactide of formula (2a), and >98% L-lactide of formula (2b). In another embodiment, the D-lactide of formula (2a), L-lactide of formula (2b), and/or rac-lactice of formula (2c) is recrystallized prior to the polymerization to form the PLA of formula (I).

[0023] In accordance with another aspect, there is provided a process for a polymerizing a cyclic monomer, wherein the process is a ring-opening melt polymerization comprising: reacting the cyclic monomer in the presence of a catalyst of formula (3a) and/or (3b)

(3b),

wherein the dashed line represents an optional double bond;

each R² is independently hydrogen, halogen, optionally substituted linear or branched CMS alkyl (e.g., C1-10 alkyl), optionally substituted cyclic C3-18 alkyl (e.g., cyclic C3-12 alkyl), or optionally substituted phenyl or SiR', where R' is alkyl or aryl; each R³ is hydrogen, optionally substituted linear or branched CMS alkyl (e.g., Ci- 10 alkyl), or optionally substituted cyclic C3-18 alkyl (e.g., cyclic C3-12 alkyl); each R is independently OR⁴, NR⁴ ₂, SR⁴, or CH₂SiR⁴ ₃, where R⁴ is hydrogen, optionally substituted linear or branched CMS alkyl (e.g., C1-5 alkyl), such as a fluoro-substituted alkyl, or optionally substituted linear or branched (C1-12) alkylcarbonyl (e.g., (Ci-5)alkylcarbonyl), such as C(0)CH20CH3; and each R⁵ is independently hydrogen, optionally substituted linear or branched CMS alkyl (e.g., C1-10 alkyl), optionally substituted cyclic C3-18 alkyl (e.g., cyclic C3-12 alkyl) or, when there is a C-N double bond, absent;

until polymerization is deemed complete, to form a polymer comprising a M_w≥160 000, a crystallinity of >80% and/or a T, >170°C.

[0024] In one embodiment, the cyclic monomer is a lactide, lactone, a di-lactone, a lactam, an epoxide, a cyclic carbonate, a cyclic anhydride, a cyclic amide, or a cyclic ester. In another embodiment, the lactide is D-lactide of formula (2a), L-lactide of formula (2b), and/or rac-lactice of formula (2c)

(2a) (2b) (2c).

[0025] In another embodiment, the lactide comprises <10% D-lactide of formula (2a), and >90% L-lactide of formula (2b); or, <8% D-lactide of formula (2a), and >92% L-lactide of formula (2b); or, 6% D-lactide of formula (2a), and >94% L-lactide of formula (2b); or, <4% D-lactide of formula (2a), and >96% L-lactide of formula (2b); or, <2% D-lactide of formula (2a), and >98% L- lactide of formula (2b). In yet another embodiment, the D-lactide of formula (2a), L-lactide of formula (2b), and/or rac-lactice of formula (2c) is recrystallized prior to polymerization.

[0026] In another embodiment, the process further comprises reacting the D-lactide of formula (2a), L-lactide of formula (2b), and/or rac-lactide of formula (2c) with the catalyst of formula (3a) and/or (3b), in the presence of a chain transfer agent (CTA). In another embodiment, the chain transfer agent is benzyl alcohol, ethanol, isopropanol, or tert-butanol. In yet another

embodiment, the lactide:catalyst:CTA is 1000:1 :5; or, 1000:1 :0; or, 5000:1 :5; or, 5000:1 :0; or, 10 000:1 :5; or, 10 000:1 :0; or, 15 000:1 :5; or, 15 000:1 :0; or, 20 000: 1 :5; or, 20 000:1 :0.

[0027] In one embodiment, the catalyst of formula (3a) and/or (3b) is (i) dissolved in a solvent, and (ii) added to the cyclic monomer to catalyze the ring-opening melt polymerization. In another embodiment, the solvent is an anhydrous, non-Lewis basic solvent. In another embodiment, the solvent is toluene; or isopropyl acetate; or, tert-butyl acetate; or, methyl tert-butyl ether' or, xylenes; or, cymene; or, a chlorinated solvent; or, a bulky ester solvent; or, a bulky ether solvent; or, an aromatic solvent.

[0028] In one embodiment, the melt polymerization occurs at <180°C; or, <160°C; or, <140°C; or <120°C; < 100°C.

BRIEF DESCRIPTION OF THE FIGURES

[0029] For a better understanding of the application as described herein, as well as other aspects and further features thereof, reference is made to the following description which is to be used in conjunction with the accompanying tables and drawings, where: [0030] Table 1 delineates a summary of representative PLA syntheses results (Process #1);

[0031 ] Table 2 delineates overall results of ASTM D638 Standard Test Method for Tensile Properties of Plastics with respect to the herein described PLA (Process #2); and

[0032] Table 3 delineates detailed results of ASTM D638 Standard Test Method for Tensile Properties of Plastics with respect to the herein described PLA (Process #2).

[0033] Figure 1 depicts a proton nuclear magnetic resonance (¹H NMR) spectrum of a mixture of lactide and PLA;

[0034] Figure 2 depicts a stress-strain plot of a control PLA tested via a ASTM D638 Standard Test Method for Tensile Properties of Plastics; and

[0035] Figure 3 depicts a stress-strain plot of a the PLA as described herein (PLAi_n), tested via a ASTM D638 Standard Test Method for Tensile Properties of Plastics.

DETAILED DESCRIPTION

[0036] Definitions

[0037] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs.

[0038] As used in the specification and claims, the singular forms "a", "an" and "the" include plural references unless the context clearly dictates otherwise.

[0039] The term "comprising" as used herein will be understood to mean that the list following is non-exhaustive and may or may not include any other additional suitable items, for example one or more further feature(s), component(s) and/or ingredient(s) as appropriate.

[0040] As used herein, "halogen", "halide", or "halo" refers to F, CI, Br or I.

[0041 ] As used herein, "alkyl" refers to a linear, branched or cyclic, saturated, unsaturated, or partially unsaturated hydrocarbon group, which can be unsubstituted or is optionally substituted with one or more substituent. Examples of saturated straight or branched chain alkyl groups include, but are not limited to, methyl, ethyl, 1 -propyl, 2-propyl, 1 -butyl, 2-butyl, 2-methyl-1 - propyl, 2-methyl-2-propyl, 1 -pentyl, 2-pentyl, 3-pentyl, 2-methyl-1 -butyl, 3-methyl-1 -butyl, 2-methyl-3-butyl, 2, 2-dimethyl-1 -propyl, 1 -hexyl, 2-hexyl, 3-hexyl, 2-methyl-1 -pentyl, 3-methyl-1 - pentyl, 4-methyl-1 -pentyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl,

2,2-dimethyl-1 -butyl, 3,3-dimethyl-1 -butyl and 2-ethyl-1 -butyl, 1-heptyl and 1 -octyl. As used herein the term "alkyl" encompasses cyclic alkyls, or cycloalkyl groups. The term "cycloalkyl" as used herein refers to a non-aromatic unsaturated or saturated monocyclic, bicyclic or tricyclic hydrocarbon ring system containing at least 3 carbon atoms. Examples of C3-C12 cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, norbornyl, adamantyl, bicyclo[2.2.2]oct-2-enyl, and bicyclo[2.2.2]octyl.

[0042] As used herein, the term "alkenyl" refers to a straight, branched, or cyclic hydrocarbon group containing at least one double bond, which can be unsubstituted or optionally substituted with one or more substituents.

[0043] As used herein, "alkynyl" refers to an unsaturated, straight, or branched chain hydrocarbon group containing at least one triple bond, which can be unsubstituted or optionally substituted with one or more substituents.

[0044] As used herein, "allenyl" refers to a straight or branched chain hydrocarbon group containing a carbon atom connected by double bonds to two other carbon atoms, which can be unsubstituted or optionally substituted with one or more substituents.

[0045] As used herein, "aryl" refers to hydrocarbons derived from benzene, or a benzene derivative, that are unsaturated aromatic carbocyclic groups of from 6 to 100 carbon atoms, in some embodiments 6 to 50 carbon atoms, in other embodiments 6 to 25 carbon atoms, and in still other embodiments 6 to 15 carbon atoms. The aryls may have a single ring or multiple rings, which may or may not be a fused ring system. The term "aryl" as used herein also includes substituted aryls. Examples include, but are not limited to phenyl, naphthyl, xylene,

phenylethane, substituted phenyl, substituted naphthyl, substituted xylene, substituted phenylethane and the like. As used herein, "heteroaryl" refers to an aryl that includes from 1 to 10, and in other embodiments 1 to 4, heteroatoms selected from oxygen, nitrogen and sulfur, which can be substituted or unsubstituted. [0046] As used herein, "substituted" refers to the structure having one or more substituents whose presence does not impede a desired reaction or desired physical and/or chemical properties; or, whose presence facilitates and/or improves a desired reaction or desired physical and/or chemical properties. A substituent is an atom or group of bonded atoms that can be considered to have replaced one or more hydrogen atoms attached to a parent molecular entity. Examples of substituents include, but are not limited to, aliphatic groups (e.g., alkyl, alkenyl, alkynyl, etc.), halide, carbonyl, acyl, dialkylamino, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, alkoxycarbonyl, amido, alkylthiocarbonyl, alkoxy, aryloxy, phosphate ester, phosphonato, phosphinato, cyano, amino, acylamino, tertiary amido, imino, alkylthio, arylthio, sulfonato, sulfamoyl, tertiary sulfonamido, nitrile, trifluoromethyl, trifluoromethoxy, heterocyclics, aromatic, and heteroaromatic moieties, ether, ester, boron-containing moieties, tertiary phosphines, and silicon-containing moieties. Silicon-containing moieties include silylated complexes such as S1R3 where R is an alkyl or aryl or combinations thereof.

[0047] The terms "dispersity" and "polydispersity" refer to the dispersions of distributions of molar masses (or relative molecular masses, or molecular weights) and degrees of

polymerization in polymeric systems. (INTERNATIONAL UNION OF PURE AND APPLIED CHEMISTRY- Dispersity in polymer science lUPAC Recommendations 2009; Pure Appl. Chem., Vol. 81, No. 2, pp.351 -353, 2009) The polydispersity index (PDI) is defined as the weight- average molecular weight divided by the number-average molecular weight (Mw/Mn). Both the Mw and the Mn can be determined by gel permeation chromatography or GPC. GPC can also be used in conversion experiments to determine the molecular weights of polymer samples. Polydispersity can be measured using GPC, providing a distribution of molecular weights (M_n). Molecular weights are measured versus standards and corrected (M_n ^c) for changes in elution times.

[0048] The term "tacticity," as used herein, refers to the relative stereochemistry of adjacent chiral centres within a polymer. Two adjacent structural units in a polymer are referred to as a dyad. When the two structural units have the same stereochemistry, the dyad is a "meso" dyad. If the two adjacent structural units have different stereochemistry, the dyad is a "racemic" dyad. Isotacticity is the extent to which a polymer is isotactic, where an isotactic polymer is one composed of meso dyads. The degree of isotacticity of a polymer can be quantified using P_m values, where P_m is the probability of finding meso dyads in a polymer. A P_m of 1 is a polymer that is 100% isotactic and a P_m of 0.5 is a polymer with no tacticity, in other words it is atactic.

[0049] As used herein, the phrase 'until polymerization is deemed complete' refers to a user-set end-point, wherein the user will allow the polymerization of monomers to continue until the user's desired/required reaction conditions, reaction mixture composition, polymeric physical characteristics, and/or polymeric chemical characteristics are achieved; non-limiting examples of which include: a %conversion of monomeric units into polymer; a desired polymeric molecular weight; a % crystillinity; a desired polymeric T_m; etc.

[0050] Described herein is a poly(lactic acid) (PLA), wherein said PLA has a % crystallinity (estimated by Heat of Crystallization using DSC analysis) in a range of from about 35% to about 90%, a melt temperature (T_m) in a range of from about 145°C to about 190°C, and/or a M_w in a range from about 120 000 to about 190 000. In one embodiment, the % crystallinity of the PLA ranges from about 60% to about 85%, the T_m ranges from about 150°C to about 180°C, and the Mw ranges from about 150 000 to about 180 000. In accordance with one embodiment, the PLA has a crystallinity of >80%, a T_m >170°C, and/or a M_w≥160 000.

[0051 ] Also described herein is a process for producing crystalline PLA, which is a ring-opening melt polymerization process that employs a salen indium complex as a catalyst. The salen indium complexes have been previously disclosed in International PCT Application No.

PCT/CA2013/050191 , which is expressly incorporated herein in its entirety, and demonstrated to be useful as catalysts in stereoselective polymerizations of lactide, and/or synthesizing isotactically enriched poly(lactic acids). Further described herein is a process of producing crystalline PLA via a ring-opening polymerization, wherein the salen indium catalyst is first dissolved in a minimal amount of solvent prior to its addition to lactide monomer(s).

[0052] Described herein is also a process for polymerizing cyclic monomers (e.g., lactides, lactones, lactams, cyclic esters, etc.) via a ring-opening melt polymerization that employs the salen indium complexes that were previously disclosed in International PCT Application No. PCT/CA2013/050191 ; the resultant polymers comprising a high molecular weight, a high crystallinity, and/or a high T_m. In accordance with one embodiment, the resultant polymers comprise a M_w≥160 000, a crystallinity of >80% and/or a T_m≥170°C. [0053] Salen indium complexes

[0054] Typically, "salen ligand" is used to refer to a class of chelating ligands derived from salicylaldehydes, and their corresponding complexes. Salen ligands comprise two imine nitrogens. However, for simplicity's sake, "salen ligand" and "salen complex" are used to also refer to "salan" ligands and complexes, in which the two nitrogens are saturated (i.e. include two amine nitrogens rather than two imine nitrogens) and "salalen" ligands and complexes, in which one nitrogen is an imine nitrogen and the other is an amine nitrogen.

[0055] In accordance with one aspect, the complex has the structure of formula (3a) and/or its corresponding dimer of formula (3b):

wherein the dashed line represents an optional double bond;

each R² is independently hydrogen, halogen, optionally substituted linear or branched C1-18 alkyl (e.g., C1-10 alkyl), optionally substituted cyclic C3-18 alkyl (e.g., cyclic C3-12 alkyl), optionally substituted aryl (e.g. phenyl or napthyl) or SiR', where R' is alkyl or aryl; each R³ is hydrogen or optionally substituted linear or branched CMS alkyl (e.g., C1-10 alkyl), optionally substituted cyclic C3-18 alkyl (e.g., cyclic C3-12 alkyl); each R is independently OR⁴, NR⁴ ₂, SR⁴, or CH₂SiR⁴ ₃, where R⁴ is hydrogen, optionally substituted linear or branched C MS alkyl (e.g., C1-5 alkyl), such as a fluoro-substituted alkyl, or optionally substituted linear or branched (Ci-i2)alkylcarbonyl (e.g., (Ci-5)alkylcarbonyl), such as C(0)CH₂OCH₃; and each R⁵ is independently hydrogen, optionally substituted linear or branched C MS alkyl (e.g., C1-10 alkyl), optionally substituted cyclic C3-18 alkyl (e.g., cyclic C3-12 alkyl) or, when there is a C-N double bond, absent.

[0056] In accordance with one embodiment, each R¹ is an optionally substituted methylene, ethylene, butylene or pentylene,

[0058] In accordance with another embodiment, each R¹ is a substituted C2-5 alkylene, such as,

[0059] In accordance with one embodiment, each R² is independently hydrogen, optionally substituted linear or branched CMS alkyl (e.g., CMO alkyl), optionally substituted cyclic C3-18 alkyl (e.g., cyclic C3-12 alkyl), or optionally substituted phenyl.

[0060] In accordance with another embodiment, each R³ is hydrogen. [0061 ] In accordance with one embodiment, each R is independently OR⁴, NR¾, SR⁴, or CH2SiR⁴3, where R⁴ is hydrogen, optionally substituted linear or branched CMS alkyi (e.g., C1-5 alkyi), such as a fluoro-substituted alkyi, or optionally substituted linear or branched (Ci- i2)alkylcarbonyl (e.g., (Ci-5)alkylcarbonyl), such as C(0)CH20CH3.

[0062] In accordance with another embodiment, each R⁵ is independently hydrogen, optionally substituted linear or branched C1-3 alkyi (e.g., C1-10 alkyi), or, when there is a C-N double bond, absent.

[0063] In accordance with another embodiment, the catalyst has a formula (3a) and/or (3b), wherein the dashed line represents an optional double bond; 1 is an optionally substituted

each R² is independently hydrogen, optionally substituted linear or branched CMS alkyi (e.g., C1-10 alkyi), optionally substituted cyclic C3-18 alkyi (e.g., cyclic C3-12 alkyi), or optionally substituted phenyl; each R³ is hydrogen; each R is independently OR⁴, NR⁴ ₂, SR⁴, or CH₂SiR⁴3, where R⁴ is hydrogen, optionally substituted linear or branched CMS alkyi (e.g., C1-5 alkyi), such as a fluoro-substituted alkyi, or optionally substituted linear or branched (Ci_i2)alkylcarbonyl (e.g., (Ci-5)alkylcarbonyl), such as C(0)CH₂OCH₃; and each R⁵ is independently hydrogen, optionally substituted linear or branched C1-3 alkyl (e.g., C1-10 alkyl), or, when there is a C-N double bond, absent.

[0064] In accordance with one embodiment, the catalyst of formula 3a and/or 3b comprises a ligand having one of the following structures:

a corresponding dimer of one of the above structures.

[0066] In an alternative embodiment, substituent R consists of a hemi-labile donor system. For example, when R is OR⁴, and R⁴ is an alkoxy substituted alkyl (e.g., alkoxy-substituted methyl), the monomeric form of the catalyst would have the following structure (please note that, in the following structures, Ri is equivalent to R² as described above; R2 is a component of R¹ as described above; and R is a component of R/R⁴ as described above):

[0067] In this example, the complex can consist of both a 6 coordinate and 5 coordinate catalyst.

[0068] In accordance with certain alternative embodiments, the salen indium ligand comprises bridging ligands that are not based on alkoxides. For example, the bridging ligand can be a sulfide or an amide as shown in the following structures (please note that, in the following structures, Ri is equivalent to R² as described above; R₂ is a component of R¹ as described above; and R is a component of R/R⁴ as described above):

[0069] As would be readily understood by a worker skilled in the art, the dimeric catalyts can comprise two different salen ligands; it is not necessary for each indium centre to be complexed by the same ligand. The following structure generally illustrates a catalyst in dimeric form that comprises mixed salen ligands (please note that, in the following structure, R is a component of R/R⁴ as described above):

[0070] The dimeric catalyst can comprise mixed bridging ligands. More specifically, in the dimeric form of the catalyst, the two R substituents can be the same or different. This is illustrated in the structures of alternative embodiments of the salen indium complexes as described herein, shown below (please note that, in the following structures, Ri is equivalent to R² as described above; R2 is a component of R¹ as described above; and R is a component of R/R⁴ as described above):

[0071 ] In accordance with one embodiment, the complex has the structure:

or the corresponding dimer.

[0072] In accordance with one embodiment, R¹ is

[0073] In accordance with another embodiment, at least one R² is an optionally substituted C1-5 alkyl, an optionally substituted aryl, an optionally substituted C3-C12 cyclic alkyl, or Si(aryl)3; R³ is H and R⁴ is C1-3 alkyl. In an another embodiment at least one R² is an optionally substituted C1-5 alkyl or an optionally substituted C3-12 cyclic alkyl.

[0074] Specific, non-limiting, examples of chiral salen indium catalysts are:

(R,R)-2,

(S,S)-2. [0075] In one embodiment, the catalysts provide isotactic enrichment of poly(lactic acid) during polymerization with a lactide. In accordance with another embodiment, the substituent Ri is chiral. In accordance with one embodiment, the stereochemistry of Ri is (R,R). In fact, isotacticity can be obtained using a racemic or achiral salen indium catalyst irrespective of the stereochemistry of the monomers employed in the polymerization

[0076] Polymerization Processes

[0077] The salen indium catalysts identified above can be used for production of PLA from a ring-opening melt polymerization of cyclic esters such as, for example, lactides. Lactides useful in the application, as described herein, can be D-lactide, L-lactide, meso-lactide or rac-lactide, wherein rac-lactide is a 50:50 mixture of D-lactide and L-lactide. In polymerizations, the lactide can be a mixture of D and L-lactides that is not a 50:50 mixture. For example, a common, commercially available lactide, that can be used in the polymerization methods described herein, is a mixture of 98% L-lactide and 2% D-lactide. In one embodiment, the L-lactide to D- lactide ratio (% wt/wt) is from about 90% to about 99.9%. In another embodiment, the L-lactide content is approximately 96-98%. In yet another embodiment, the L-lactide content is >98%. In some embodiments, the commercially available lactide is recrystallized before use.

[0078] In some embodiments, the cyclic ester monomers used in the polymerization methods, as described herein, include pendant functional groups. For example, a cyclic ester monomer used in a polymerization method can include pendant cross-linkable functional groups; a non- limiting example of one such cross-linkable functional group is a vinyl group, or a vinyl group derivative, such as, but not limited to, divinyl, or styrenyl. Other non-limiting examples of a pendant cross-linkable group include diols or diamines. This example has the added advantage of being useful in methods for manufacturing cross-linked PLA.

[0079] In accordance with one embodiment, there is provided a method comprising polymerizing a cyclic ester monomer, or combination of cyclic ester monomers, with a salen indium catalyst, as described herein, under conditions suitable for ring-opening melt polymerization. A plurality of different cyclic ester monomers can be polymerized at the same time, or during different times of the entire polymerization process. [0080] The ring-opening polymerization of the process, as described herein, can be a living polymerization; that is, polymerizing steps can be living polymerizing steps in the processes disclosed herein.

[0081 ] In living polymerizations, cyclic ester monomers are polymerized at very low polymer chain transfer and termination rates (e.g., ability of growing polymer chains to terminate is substantially removed). The result can be that the polymer chains grow at a more constant rate (compared to traditional chain-growth polymerization), and the polymer chain lengths remain very similar (e.g., have a very low polydispersity index).

[0082] The ring-opening polymerization of the process, as described herein, can further be an immortal ring opening polymerization; that is, polymerizing steps can be immortal polymerizing steps in the processes disclosed herein.

[0083] In immortal ring-opening polymerization (iROP) of a cyclic ester monomer, external nucleophiles can act as both initiators and chain transfer agents in conjunction with a catalyst.

[0084] In accordance with one embodiment, there is provided a process of making polylactic acid comprising polymerizing lactide in the presence of a salen indium complex as described herein.

[0085] In accordance with another embodiment, the polylactic acid has a polydispersity index of about 2.0. In one embodiment, the polylactic acid has a polydispersity index of less than about 1 .7. In another embodiment, the polylactic acid has a polydispersity index less than about 1 .5.

[0086] In accordance with another embodiment, there is provided an isotactically enriched polylactic acid produced by the disclosed process. In one embodiment, the isotactically enriched polylactic acid has a P_m, or isotacticity, of greater than 0.5, or between about 0.6-1 .0. In another embodiment, the isotactic enrichment is between about 0.7-1.0.

[0087] In accordance with the application, as described herein, the polymerization reaction is performed using a bulk, or melt process in which a salen indium complex is mixed with a cyclic ester monomer, or combination of monomers, in the absence of a solvent or in the presence of a minimal amount of solvent. [0088] In a melt polymerization process, polymerization occurs in a melt phase. The herein described reaction mixture is heated to a temperature of greater than the melting point of the monomer, or combination of monomers, for an appropriate amount of time to allow the polymerization to proceed (e.g., an hour or more). In one embodiment, the melt polymerization process is performed at a temperature of about 125°C or more, for example, at a temperature of from about 125°C to about 250°C, or from about 100°C to about 200°C. In specific examples, the melt polymerization is performed at about 1 10°C, or about 130°C, or about 160°C, or about 190°C. In one embodiment, the melt temperature is in the range of from about 125°C to about 180°C.

[0089] In accordance with certain embodiments, the monomencatalyst molar ratio is from about 50:1 up to about 20,000:1 .

[0090] In accordance with one aspect, there is provided a ring-opening melt polymerization process, comprising dissolving the salen indium catalyst in a minimal amount of solvent; melting the monomer(s); adding the dissolved catalyst to the melted monomer(s); and reacting the monomer(s) in the presence of the catalyst, until polymerization is deemed complete.

[0091 ] In accordance with one embodiment of the process, the minimal amount of solvent corresponds to the amount of solvent required to dissolve/solubilize the herein described salen indium catalysts. As would be understood by one skilled in the art, choice of solvent will depend, at least in part, on catalyst structure and its corresponding solubility, and, optionally, the properties of the monomers and/or product of the reaction. In one embodiment, the solvent is an anhydrous, non-Lewis basic solvent, non-limiting examples of which include: toluene; or isopropyl acetate; or, tert-butyl acetate; or, methyl tert-butyl ether' or, xylenes; or, cymene; or, a chlorinated solvent; or, a bulky ester solvent; or, a bulky ether solvent; or, an aromatic solvent.

[0092] It was found that solubilizing the salen indium catalyst in a minimal amount of solvent provided reaction mixture homogeneity, polymeric molecular weights of >160 000, and rapid reaction rates (e.g. near quantitative conversion within 1 -2 min). Without wishing to be bound by theory, it was postulated that the increase in reaction mixture homogeneity contributed to observed polymer molecular weights of >160 000, and reaction rates of approximately 1 -2 min. [0093] The melt process described herein optionally employs a chain transfer agent ("CTA"), however, in particular embodiments a CTA is not used in the process. In the case where a CTA is employed the catalyst:CTA molar ratio can be from about 1 :0 to about 1 : 10. The CTA is optionally used in the process to have an effect on the living polymerization characteristics and the ultimate molecular weight of the polymer. If used, in one embodiment, the CTA can be a hydroxyl compound, ROH, where R can be a linear, branched or cyclic Ci to Ce alkyl, aryl or alkylaryl. In another embodiment, the CTA benzyl alcohol, ethanol, isopropanol, or tert-butanol.

[0094] In one embodiment of the polymerization processes described herein, there is a ring- opening melt polymerization process, wherein the cyclic monomer can be a lactide, a lactone, a di-lactone, a lactam, an epoxide, a cyclic carbonate, a cyclic anhydride, a cyclic amide, or a cyclic ester.

[0095] In one embodiment, non-limiting examples of possible cyclic ester monomers include β- butyrolactone, 4-(but-3-en-1 -yl)oxetan-2-one,

or a stereoisomer thereof.

[0096] In an alternative embodiment, the herein described polymerization processes may be applied to a ring-opening melt co-polymerization process, wherein the co-polymerization process comprises reacting any combination of the herein described cyclic monomers in the presence of the herein described salen indium catalysts. In one embodiment, said cyclic monomers are reacted sequentially to form a block copolymer. In another embodiment, said cyclic monomers are reacted simultaneously to form a random copolymer.

[0097] In one embodiment, said copolymer can be produced by reacting (i) two or more different lactides; (ii) two or more different lactones; (iii) two or more different di-lactones; (iv) two or more different lactams; (iv) two or more different epoxides; (iv) two or more different cyclic carbonates; (iv) two or more different cyclic anhydrides; (v) two or more different cyclic amides; or (vi) two or more cyclic esters. In another embodiment, the copolymer can be produced by reacting two or more different cyclic monomers (e.g., polymerize a lactide and lactone together to give a copolymer), wherein said cyclic monomers can be a lactide, a lactone, a di-lactone, a lactam, an epoxide, a cyclic carbonate, a cyclic anhydride, a cyclic amide, or a cyclic ester.

[0098] To gain a better understanding of the invention described herein, the following examples are set forth. It should be understood that these examples are for illustrative purposes only. Therefore, they should not limit the scope of this invention in any way.

WORKING EXAMPLES

[0099] EXAMPLE 1 : Process #1 - Representative synthesis of isotactic PLA and Results Thereof

[00100] General Experimental

[00101 ] All reactions were carried out under an inert atmosphere of nitrogen using either a glove box or standard Schlenk line techniques. Lactide starting materials (98%+ L-lactide isomer) was received from NatureWorks LLC and re-crystallized from a solution of isopropanol at 65°C. 4M HCI solution in dioxane and benzyl alcohol were purchased from Sigma Aldrich and used as received. Methanol and Dichloromethane (DCM) was purchased from Fisher and used as received.

[00102] All Nuclear Magnetic Resonance (NMR) spectra were recorded on a Varian 400 MHz spectrometer. Proton (¹H) NMR chemical shift was reported in ppm versus residual protons in deuterated chloroform (CDC ) at δ = 7.24 ppm. Molecular weights (M_n, M_w) were determined by gel permeation chromatography (GPC), on a Varian PL-GPC 50 Plus instrument using various molecular weight polystyrene samples as calibration standards. GPC samples were dissolved in THF with a concentration of approximate 3 mg/mL. The GPC samples was stirred overnight and then filtered using a 0.2 μηι polytetrafluoroethylene (PTFE) syringe filter. Melting transition temperatures (T_m) and extent of crystallinity were determined by differential scanning calorimetry (DSC), on a TA DSC Q100 instrument. DSC samples were first heated to 210 °C for a few minutes, either in instrument or in an oven, and then cooled back down to 30 °C prior to obtaining a DSC trace. DSC analysis was carried out under N2 atmosphere with heat rate of 10°C/min from 30°C to 210°C.

[00103] ¹H NMR was used to determine conversion by integrating NMR resonances corresponding to monomer and polymer methine protons. Extent of crystallinity was calculated as followed:

Crystallinity = (AH_m/AH°_m )x100%

where:

AHm - Melting enthalpy (J/g) of test sample

AH°m - Melting enthalpy of absolute crystallized polylactide, 93.1 J/g

[00104] Representative Synthesis and Analysis

[00105] In a nitrogen filled dry box, 20 g lactide and 0.039 g indium catalyst (R,R-2, see paragraph [0074]) par ere loaded into a dry 3-neck 100 ml_ round bottom flask, in that order. One of the flask's outer necks was capped with a rubber septum, while a gas adapter was added to the other. The flask's central neck was capped with a lightly greased glass stopper to seal it. The flask was then removed from the dry box and attached to a Schlenk line via a hose, wherein the hose and closed gas adapter were put under vacuum and refilled with nitrogen three times before opening the flask to a flow of nitrogen. The flask was then immersed in a recrystallization dish containing thermally conductive beads, and a thermal probe with a Teflon adapter attached. The beads' temperature was pre-set to 135°C.

[00106] Under a flow of nitrogen, the thermal probe was removed from the beads and quickly attached to the flask via the septum-capped outer neck, upon removing the rubber septum. This was done to ensure that the reaction mixture's temperature was at 135°C. An overhead stirrer, with a crescent shaped Teflon stir blade attached, was attached to the central neck by quickly removing the glass stopper under a flow of nitrogen. It took approximately 15 minutes for the lactide to melt completely. It started melting between 95-98°C and was completely molten at 105°C giving a light yellow liquid. At this point, a stir rate of 275 rpm was initiated and a timer started.

[00107] At hour marks 2, 4, 6, 8, 10, stirring was stopped and the glass adapter was briefly removed from the flask to remove an unweighed amount of the reaction mixture with a spatula. These periodic samples are used to acquire DSC, GPC and ¹H NMR spectral data. It was observed that the mixture's viscosity increased with reaction and its colour turned to a deeper yellow. At the 12 hour mark, the overhead stirrer and thermal probe were removed from the flask. The molten mixture was discharged onto a pre-weighed silicone baking pan through one of the flask's side necks. A final sample was taken for analysis while any remaining polymer product was allowed to cool overnight in a fumehood. The polymer was weighed directly on the pan to determine an approximate percent yield, due to the six removed aliquots, and then removed from the pan.

[00108] Approximately half of the polymer was used "as is" for analytical measurements. Dichloromethane (30 mL, room temperature) was added to the other half of isolated polymer to give a solution, to which 1 mL of HCI in dioxane solution was added. Resulting solution was stirred for 15 minutes in order to cleave any remaining catalyst from the polymer chain. The solution was then transferred to a separatory funnel (125 mL) and added drop-wise to methanol (600 mL), that has been previously stored at -30°C, in a 2L beaker cooled in an ice bath.

Stirring was achieved using an overhead stirrer set to 380-390 rpm. It was important that the polymer solution drops did not make contact with the solvent vortex at the flask's centre, otherwise the stir bar would become coated with precipitated polymer, which would impede stirring.

[00109] Resulting white fibres were filtered using a Biichner funnel/water aspirator with Whatman #2 filter paper and rinsed with 3 x 50 mL portions of room temperature methanol. The polymer was further dried overnight under dynamic vacuum in a vacuum oven at room temperature. Final analytical measurements were carried out with the isolated polymer. [001 10] In some examples, the PLA synthesis was carried out with a chain transfer agent (CTA), such as benzyl alcohol, which was used in this example.

[001 1 1 ] Representative lactide:catalyst:CTA ratios employed were as follows; results summarized in Table 1 :

5000 lactide: 1 catalyst : 5 benzyl alcohol;

1000 lactide: 1 catalyst : 5 benzyl alcohol; or

5000 lactide: 1 catalyst

[001 12] EXAMPLE 2: Process #2 - Representative synthesis of isotactic PLA and Results Thereof

[001 13] General Experimental

[001 14] Commercial lactide (D, L, racemic, meso, or other mixture) was used as received from Natureworks (>98% L-lactide). To facilitate the ring-opening polymerization (ROP) process, water content in the lactide was no greater than 200 ppm.

[001 15] Indium catalyst R,R-2 (see paragraph [0074]) was stored in an inert environment, such as a dry box or glove box under nitrogen atmosphere. It was observed that the catalyst was air-stable in moderate to low relative humidity (<50% RH), but sensitive to moisture; thus it was stored in a moisture-free, inert environment, and manipulated using Schlenk technique wherever possible. All glassware or lab instruments used were oven-dried or heated at 120°C to remove residual moisture prior to synthesis.

[001 16] As would be understood by one skilled in the art, ring-opening polymerization can be performed in a standard polymerization reactor (e.g. a glass-lined reactor, such as a glass resin kettle or glass-lined Parr reactor), optionally with a bottom-drain valve. The reaction vessel can be jacketed if using recirculating heating/cooling fluid for effective heat transfer, or unjacketed if heat is applied with a heating mantle. The reaction vessel can be equipped with overhead mechanical stirrer, internal thermal probe, and with adapter for charging raw materials. The reaction vessel should be placed in a well-ventilated area (e.g. fumehood). [001 17] Representative Synthesis and Analysis

[001 18] In a glove box (or dry nitrogen environment), a reaction vessel (glass resin kettle, 3000 mL, unjacketed) was charged with lactide. The reaction vessel was heated by a heating mantle equipped with rheostat temperature controller.

[001 19] Indium catalyst R,R-2 (1 .0 gram; see paragraph [0074]) was transferred into a small (25-50 mL round-bottomed flask) inside a glove box, or under dry nitrogen. The catalyst was dissolved in a small volume (15-20 mL) of dry toluene (e.g., from a Sigma-Aldrich Sure-Seal bottle). A 3 L glass reaction vessel equipped with a 50 mL dropping funnel was charged with 500 grams of lactide under nitrogen atmosphere. The reaction vessel was heated so that internal temperature was 140°C, and stirred at 50-80 rpm using a mechanical stirrer (Anchor stirrer, 14.7 cm. blade diameter, shaft diameter 0.8 cm or other integral metal stirrer). Once the lactide melted and was free flowing, the catalyst-toluene solution was transferred to the dropping funnel, and added over 20-30 seconds. After a very brief lag period, reaction occurs (concurrent exotherm approximately 20-40 degrees), and viscosity increased over 1 -2 minutes, giving a solid mass of poly(lactic acid) (PLA). Mechanical stirring then ceased.

[00120] It was determined that the thus prepared PLA could be handled two ways: the PLA could be slowly dissolved in an organic solvent (e.g. , dichloromethane, 1 -2 L), and then precipitated in a large volume of methanol (4L); alternatively, the PLA could be heated above its melting point (~180-190 °C), and then poured out of the reaction vessel while hot. The latter method was convenient for reaction vessels having a bottom drain valve. The thus isolated PLA was then cooled as a thin sheet, and small portions were used for analysis.

[00121 ] Monomer %-conversion was monitored by ¹H NMR spectroscopy. Samples of crude polymer (0.1 -0.2 g) obtained from the reaction mixture were dissolved in CDC (0.8-1 .0 mL). Monomer conversion was determined by integrating ¹H resonances corresponding to the lactide's methine protons (¹H, q, 5.03 ppm) and polymer's methine protons (¹H, q, 5.16 ppm) (Figure 1). Using a solvent dispersion of the catalyst as described above, conversions were typically >92-94%. GPC analysis showed M_w = 172 000, PDI = 1 .77. DSC analysis gives Tm~176-178 °C. [00122] EXAMPLE 3: ASTM D638 Testing on Polylactide Samples Synthesized via

Process #2

[00123] Cylindrical filaments for testing were prepared using a Tinius Olsen Extrusion

Plastometer. A polymer sample was equilibrated at an appropriate temperature for melt flow, then subjected to a 53 MPa pressure to extrude an approximately 2 mm diameter filament.

[00124] An Instron Model 3367 equipped with a 2 kN load cell was used to perform the ASTM D638 Standard Test Method for Tensile Properties of Plastics. The filament samples were conditioned for 24 hours in a 23 °C / 50% Relative Humidity controlled environment prior to testing, and tests were conducted under the same conditions. Five pieces cut from the extruded filament were measured for each sample. The filament diameter was measured in 5 places for each piece, and the average diameter was used in calculations for each section. The herein described PLA polymer (PLAin) that was used for the ASTM D638 mechanical testing was prepared via Process #2 (Example 2, see above).

[00125] From the results of the mechanical testing, it was concluded that the herein described PLA (PLAin) had similar tensile properties to the control PLA polymer (Natureworks INGEO 2003D grade (approximately 97 wt% L-lactide and 3 wt% D-lactide); T_m of approximately 161 °C; Mw approximately 250 000). This was demonstrative that the herein described indium- salen catalysts, and processes thereof, could be used in place of tin catalysts to obtain PLA of comparable mechanical strength and rigidity. Further, this was demonstrative that the PLA obtained from the herein described processes could obtain a higher T_m (≥170 °C) at lower M_w than the control PLA (M_w≥160 000). Without wishing to be bound by theory, it was postulated that the PLAin obtaining higher T_m at lower M_w could be attributed to the PLAin having a higher % crystallinity than the control PLA. For a summary of results, please see Tables 1 and 2, Figures 2 and 3.

Table 1 : Representative PLA Syntheses Result Summary

Table 2: Overall results of ASTM D638 Standard Test Method for Tensile Properties of Plastics with respect to the herein described PLA (PLAin)

Table 3: Detailed results of ASTM D638 Standard Test Method for Tensile Properties of Plastics with respect to the herein described PLA

[00126] All publications, patents and patent applications mentioned in this Specification are indicative of the level of skill of those skilled in the art to which this application pertains and are herein incorporated by reference to the same extent as if each individual publication, patent, or patent applications was specifically and individually indicated to be incorporated by reference.

[00127] The invention being thus described, it will be obvious that the same may be varied in many ways. Such variations are not to be regarded as a departure from the spirit and scope of the invention, and all such modifications as would be obvious to one skilled in the art are intended to be included within the scope of the following claims.

Claims

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1 . A poly(lactic acid) (PLA) polymer of formula (I)

(1 )

wherein the PLA has a crystallinity of >80% and a T_m >170°C.

2. The polymer of claim 1 , wherein the polymer is prepared by ring-opening polymerization, comprising: reacting R-lactide of formula (2a), S-lactide of formula (2b), and/or rac-lactide of formula (2c),

(2a) (2b) (2c), in the presence of a catalyst of formula (3a) and/or (3b)

(3a),

wherein

the dashed line represents an optional double bond; each R1 is an optionally substituted C2-5 alkylene,

each R² is independently hydrogen , halogen, optionally substituted linear or branched CMS alkyl, optionally substituted cyclic C3-18 alkyl, or optionally substituted phenyl or SiR', where R' is alkyl or aryl; each R³ is hydrogen , optionally substituted linear or branched CMS alkyl, or optionally substituted cyclic C3-18 alkyl; each R is independently OR⁴, NR⁴ ₂, SR⁴, or CH₂SiR⁴ ₃, where R⁴ is hydrogen, optionally substituted linear or branched CMS alkyl, such as a fluoro-substituted alkyl, or optionally substituted linear or branched (C1-12) alkylcarbonyl, such as C(0)CH₂OCH₃; and each R⁵ is independently hydrogen , optionally substituted linear or branched CMS alkyl, optionally substituted cyclic C3-18 alkyl, or, when there is a C-N double bond, absent; until polymerization is deemed complete, to form the PLA of formula (I)

(1). The polymer of claim 2, wherein the polymer is prepared by a melt ring-opening polymerization.

A process for producing PLA by ring-opening polymerization, comprising: reacting D-lactide of formula (2a), L-lactide of formula (2b), and/or rac-lactice of formula (2c),

each R² is independently hydrogen, halogen, optionally substituted linear or branched CMS alkyl, optionally substituted cyclic C3-18 alkyl, or optionally substituted phenyl or SiR', where R' is alkyl or aryl; each R³ is hydrogen, optionally substituted linear or branched CMS alkyl, or optionally substituted cyclic C3-18 alkyl; each R is independently OR⁴, NR⁴ ₂, SR⁴, or CH₂SiR⁴ ₃, where R⁴ is hydrogen, optionally substituted linear or branched CMS alkyl, such as a fluoro-substituted alkyl, or optionally substituted linear or branched (C1-12) alkylcarbonyl, such as C(0)CH₂OCH₃; and each R⁵ is independently hydrogen, optionally substituted linear or branched CMS alkyl, optionally substituted cyclic C3-18 alkyl, or, when there is a C-N double bond, absent;

until polymerization is deemed complete, to form the PLA of formula (I)

(1 ),

wherein, the PLA of formula (I) has a crystallinity of >80% and a T_m >170°C.

The process of claim 4, further comprising reacting the D-lactide of formula (2a), L-lactide of formula (2b), and/or rac-lactide of formula (2c) with the catalyst of formula (3a) and/or (3b), in the presence of a chain transfer agent (CTA).

6. The process of claim 5, wherein the chain transfer agent is benzyl alcohol, ethanol, isopropanol, or tert-butanol.

7. The process of claims 5 or 6, wherein lactide:catalyst:CTA is 1000:1 :5; or, 1000:1 :0; or, 5000:1 :5; or, 5000:1 :0; or, 10 000:1 :5; or, 10 000:1 :0; or, 15 000:1 :5; or, 15 000:1 :0; or, 20 000:1 :5; or, 20 000:1 :0.

8. The process of any one of claims 4 - 7, wherein the ring-opening polymerization is a melt polymerization.

9. The process of claim 8, wherein the melt polymerization occurs at <180°C; or, <160°C; or, <140°C; or, >120°C.

The process of any one of claims 4 - 9, wherein the lactide comprises <10% D-lactide of formula (2a), and >90% L-lactide of formula (2b); or, <8% D-lactide of formula (2a), and >92% L-lactide of formula (2b); or, 6% D-lactide of formula (2a), and >94% L-lactide of formula (2b); or, <4% D-lactide of formula (2a), and >96% L-lactide of formula (2b); or, <2% D-lactide of formula (2a), and >98% L-lactide of formula (2b).

1 1 . The process of any one of claims 4 - 10, wherein the D-lactide of formula (2a), L-lactide of formula (2b), and/or rac-lactice of formula (2c) is recrystallized prior to the polymerization to form the PLA of formula (I).

12. A process for producing PLA by ring-opening polymerization, comprising:

(i) dissolving a catalyst of formula (3a) and/or (3b) in a solvent,

wherein the dashed line represents an optional double bond; each R¹ is an optionally substituted C2-5 alkylene,

(2a) (2b) (2c);

(1 ),

wherein the PLA of formula (I) has (a) a M_w≥160 000, and (b) a crystallinity of >80% and/or a T_m >170°C.

13. The process of claim 12, wherein the solvent is an anhydrous, non-Lewis basic solvent.

14. The process of claim 13, wherein the solvent is toluene; or isopropyl acetate; or, tert-butyl acetate; or, methyl tert-butyl ether' or, xylenes; or, cymene; or, a chlorinated solvent; or, a bulky ester solvent; or, a bulky ether solvent; or, an aromatic solvent.

15. The process of claim 12, further comprising addition of a chain transfer agent (CTA).

16. The process of claim 15, wherein the CTA is added to the D-lactide of formula (2a), L- lactide of formula (2b), and/or rac-lactide of formula (2c), prior to the addition the catalyst of formula (3a) and/or (3b).

17. The process of claim 16, wherein the chain transfer agent is benzyl alcohol, ethanol, isopropanol, or tert-butanol.

18. The process of any one of claims 15 - 17, wherein lactide:catalyst:CTA is 1000:1 :5; or, 1000:1 :0; or, 5000:1 :5; or, 5000:1 :0; or, 10 000:1 :5; or, 10 000: 1 :0; or, 15 000:1 :5; or, 15 000:1 :0; or, 20 000:1 :5; or, 20 000:1 :0.

19. The process of any one of claims 12 - 18, wherein the ring-opening polymerization is a melt polymerization.

20. The process of claim 19, wherein the melt polymerization occurs at <180°C; or, <160°C; or, <140°C; or≥120°C.

21 . The process of any one of claims 12 - 20, wherein the lactide comprises <10% D-lactide of formula (2a), and >90% L-lactide of formula (2b); or, <8% D-lactide of formula (2a), and >92% L-lactide of formula (2b); or, 6% D-lactide of formula (2a), and >94% L-lactide of formula (2b); or, <4% D-lactide of formula (2a), and >96% L-lactide of formula (2b); or, <2% D-lactide of formula (2a), and >98% L-lactide of formula (2b).

22. The process of any one of claims 12 - 21 , wherein the D-lactide of formula (2a), L-lactide of formula (2b), and/or rac-lactice of formula (2c) is recrystallized prior to the polymerization to form the PLA of formula (I).

23. A process for a polymerizing a cyclic monomer, wherein the process is a ring-opening, melt polymerization comprising: reacting the cyclic monomer in the presence of a catalyst of formula (3a) and/or (3b)

(3b),

each R² is independently hydrogen, halogen, optionally substituted linear or branched CMS alkyl, optionally substituted cyclic C3-18 alkyl, or optionally substituted phenyl or SiR', where R' is alkyl or aryl; each R³ is hydrogen, optionally substituted linear or branched CMS alkyl, or optionally substituted cyclic C3-18 alkyl; each R is independently OR⁴, NR⁴ ₂, SR⁴, or CH₂SiR⁴3, where R⁴ is hydrogen, optionally substituted linear or branched CMS alkyl, such as a fluoro-substituted alkyl, or optionally substituted linear or branched (C1-12) alkylcarbonyl, such as C(0)CH₂OCH₃; and each R⁵ is independently hydrogen, optionally substituted linear or branched CMS alkyl, optionally substituted cyclic C3-18 alkyl, or, when there is a C-N double bond, absent;

until polymerization is deemed complete, to form a polymer comprising a M_w≥160 000, a crystallinity of >80% and/or a T_m >170°C. The process of claim 23, wherein the cyclic monomer is a lactide, a lactone, a di-lactone, a lactam, an epoxide, a cyclic carbonate, a cyclic anhydride, a cyclic amide, or a cyclic ester.

The process of claim 24, wherein the lactide is D-lactide of formula (2a), L-lactide of formula (2b), and/or rac-lactice of formula (2c)

(2a) (2b) (2c).

The process of claim 25, wherein the lactide comprises <10% D-lactide of formula (2a), and >90% L-lactide of formula (2b); or, <8% D-lactide of formula (2a), and >92% L-lactide of formula (2b); or, 6% D-lactide of formula (2a), and >94% L-lactide of formula (2b); or, <4% D-lactide of formula (2a), and >96% L-lactide of formula (2b); or, <2% D-lactide of formula (2a), and >98% L-lactide of formula (2b).

The process claims 25 or 26, wherein the D-lactide of formula (2a), L-lactide of formula (2b), and/or rac-lactice of formula (2c) is recrystallized prior to polymerization.

The process of claim 23, further comprising reacting the D-lactide of formula (2a), L-lactide of formula (2b), and/or rac-lactide of formula (2c) with the catalyst of formula (3a) and/or (3b), in the presence of a chain transfer agent (CTA).

The process of claim 28, wherein the chain transfer agent is benzyl alcohol, ethanol, isopropanol, or tert-butanol.

The process of claims 28 or 28, wherein lactide:catalyst:CTA is 1000: 1 :5; or, 1000:1 :0; or, 5000:1 :5; or, 5000:1 :0; or, 10 000:1 :5; or, 10 000:1 :0; or, 15 000:1 :5; or, 15 000:1 :0; or, 20 000:1 :5; or, 20 000:1 :0.

31 . The process of claim 23, wherein the catalyst of formula (3a) and/or (3b) is (i) dissolved in a solvent, and then (ii) added to the cyclic monomer to catalyze the ring-opening melt polymerization.

32. The process of claim 31 , wherein the solvent is an anhydrous, non-Lewis basic solvent.

33. The process of claim 32, wherein the solvent is toluene; or, tert-butyl acetate; or, methyl tert-butyl ether' or, xylenes; or, cymene; or, a chlorinated solvent; or, a bulky ester solvent; or, a bulky ether solvent; or, an aromatic solvent.

34. The process of any one of claims 23 to 33, wherein the melt polymerization occurs at <180°C; or, <160°C; or, <140°C; or <120°C; < 100°C.