Process for polymerizing lactide using liquid catalyst formulations

Abstract

The present invention relates to a method for polymerizing lactide, comprising the steps of: a) preparing a liquid catalyst formulation comprising a catalyst, an initiator, and lactide; and b) contacting the liquid catalyst formulation prepared in step a) with lactide and polymerizing the lactide in the presence of the liquid catalyst formulation to form polylactide. The present invention further provides a liquid catalyst formulation and uses thereof for polymerizing lactide.

Description

[Technical field]

[0001] The present invention relates to a process for the preparation of polylactide, in particular to a process for preparing polylactide by melt polymerization of lactide in the presence of a liquid catalyst formulation. The present invention also relates to the use of the liquid catalyst formulation for polymerizing lactide. [Background technology]

[0002] Much attention is currently focused exclusively on polylactide, also called polylactic acid and abbreviated as PLA. PLA is an aliphatic polyester that can be produced from essentially renewable resources. Such production can involve the fermentation of starch, sugars, or other renewable organic substrates into lactic acid.

[0003] PLA can in principle be synthesised by direct polycondensation of lactic acid, i.e. lactic acid monomers, but this has the drawback that high molecular weights are not easily attained.

[0004] Thus, PLA is usually prepared by ring-opening polymerization (ROP) of lactide, a cyclic dimer of lactic acid, which is usually produced by polycondensation of lactic acid to PLA oligomers, followed by depolymerization of these oligomers by the so-called "back-biting" mechanism in the presence of a suitable catalyst. After purification, the produced lactide can be converted to PLA of controlled molecular weight using ring-opening polymerization (ROP) in the presence of a polymerization catalyst. Ring-opening polymerization allows control of the polymerization process and the structure of the PLA produced thereby. Using this method, PLA of high molecular weight can be produced.

[0005] A wealth of potential catalysts for lactide polymerization exists, many of which rely on insoluble complexes. Typically, such catalysts are used on a batch scale under solvent or solid state conditions. For example, the compound stannous octoate or stannous octoate (known in the prior art as Sn(Oct) 2Stannous bis(2-ethyl-hexanoate), also called stannous bis(2-ethyl-hexanoate), is well known as a polymerization catalyst in the production of PLA under industrial large-volume conditions. WO 2009 / 121830, for example, describes a method for preparing polylactide, in which stannous octoate is used as a polymerization catalyst. When the polymerization conditions are properly selected, this method can be used to obtain high-quality PLA. Under such conditions, the use of stannous octoate as a catalyst in the lactide-to-PLA process results in a desirable high polymerization rate, allowing for a polymer resin with relatively high melt stability and low racemization rate.

[0006] Another example is WO 2014 / 177543, which reports the use of metal coordination compounds as active catalysts for the ring-opening polymerization of lactide. One example is a zwitterionic zirconium(IV) complex. The polymerization reaction disclosed in this document consists of mixing lactide with this catalyst to obtain a reaction mixture in which lactide is polymerized and then proceeds to obtain polylactide in the liquid state at a temperature of at least 150° C. The polylactide is subsequently solidified and recovered. The catalyst is added to the mixture in the solid state (as a powder) and dissolves in the lactide monomer melt during use.

[0007] Although the above catalyst system can work well under optimized polymerization conditions, it seems that there is great interest in alternative polymerization methods and catalyst systems to expand the possibilities in the production of PLA grades with different or improved properties or characteristics.In addition, there is still a continuous demand in the art to find improved methods for the polymerization of lactide and improved catalyst systems for use therein. [Prior art documents] [Patent documents]

[0008] [Patent Document 1] International Publication No. 2009 / 121830 Brochure [Patent Document 2] International Publication No. 2014 / 177543 Brochure Summary of the Invention [Problem to be solved by the invention]

[0009] It is therefore an object of the present invention to provide an improved method for the polymerization of lactide and an improved catalyst system for use therein. In particular, it is an object of the present invention to provide a polymerization process that is more efficient and / or exhibits improved reaction kinetics. Another object of the present invention is to provide a catalyst system for use in the polymerization of lactide that is convenient and efficient to use. It is also an object of the present invention to provide a polymerization process that makes it possible to prepare polylactides using solid polymerization catalysts. It is also an object of the present invention to provide a polymerization process that makes it possible to prepare polylactides with well-defined properties. [Means for solving the problem]

[0010] It has now surprisingly been found that the above needs and objectives can be achieved, individually or in any combination, by a process for the polymerization of lactide as defined herein, and by the use of a liquid catalyst formulation as defined herein.

[0011] In particular, according to a first aspect, the present invention provides a method for producing ... composition comprising the steps of: a) preparing a liquid catalyst formulation comprising a catalyst, an initiator and a lactide; b) contacting lactide with the liquid catalyst formulation prepared in step a) and polymerizing said lactide in the presence of said liquid catalyst formulation to form polylactide; The present invention relates to a method for polymerizing lactide, comprising the steps of:

[0012] The present invention relates to a) preparing a liquid catalyst formulation comprising a catalyst, an initiator and a lactide; b) contacting lactide with the liquid catalyst formulation prepared in step a) and polymerizing said lactide in the presence of said liquid catalyst formulation to form polylactide; A method for polymerizing lactide is provided, comprising: wherein the catalyst is a metal coordination compound; wherein the metal is at least one of Zr or Hf; wherein the parent ligand of said compound is of formula (I) [ka] Wherein R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 is halogen, hydroxyl, C 1~10 Alkyl, haloC 1~10 Alkyl, C 1~10 Alkoxy and HaloC 1~10 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, H, halogen, -NO 2 and C 1~10 are each independently selected from the group consisting of hydrocarbyl groups.

[0013] In another aspect, the present invention relates to a liquid catalyst formulation comprising a catalyst as defined herein, an initiator and a lactide.

[0014] In another aspect, the present invention relates to the use of a liquid catalyst formulation according to the present invention for polymerizing lactide.

[0015] The present invention further provides a polylactide obtained or obtainable by the process according to the present invention.

[0016] The inventors have now found that it is possible to formulate an otherwise insoluble catalyst complex by pre-reaction with (small amounts of) lactide and initiator. This allows to generate a stable liquid catalyst formulation that can be easily dosed and added to the melt polymerization process of lactide to achieve very fast ROP kinetics. The reaction kinetics obtained in the process according to the invention, in which such a liquid formulation is applied, are significantly higher than those reported for the prior art reactions. Thus, the polymerization process according to the invention advantageously allows to use solid polymerization catalysts in the preparation of polylactides. In one particular embodiment of the process according to the invention, the liquid catalyst formulation is prepared by mixing the catalyst provided in solid form in step a) with the initiator and lactide.

[0017] The liquid catalyst formulation as applied in the method according to the present invention is a stable liquid. When introduced into molten lactide under industrially relevant polymerization conditions as performed by the present method, the catalyst formulation achieves extremely fast and predictable kinetics with no catalyst induction period at extremely low metal concentrations. Thus, the method according to the present invention produces polylactic acid with well-defined properties, such as well-defined molecular weight and / or low polydispersity.

[0018] Another advantage of this approach is that only the reactants used in the polymerization process are used in the method. Surprisingly, this means that the polymerization process according to the invention can be carried out without adding further (extraneous) reactants during the polymerization step, such as extraneous solvents or further initiators.

[0019] The independent and dependent claims set out particular and preferred features of the invention. Features from the dependent claims may be combined with features of the independent claims or other dependent claims as appropriate.

[0020] The above and other characteristics, features and advantages of the present invention will become apparent from the following detailed description, taken in conjunction with the accompanying drawings, which illustrate, by way of example, the principles of the invention. [Brief description of the drawings]

[0021] [Figure 1] 1 shows a reaction scheme used to prepare a liquid catalyst formulation according to the present invention. The term "Complex 1" as used in FIG. 1 refers to the Zr coordination compound as described in Example 1. [Diagram 2] 1 depicts a graph plotting the amount of PLA formed as a function of time for polymerization reactions in accordance with the present invention compared to comparative polymerization reactions. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0022] When describing the present invention, the terms used shall be construed in accordance with the following definitions, unless the context dictates otherwise.

[0023] Unless otherwise defined, all terms used in disclosing the present invention, including technical and scientific terms, have the meanings commonly understood by one of ordinary skill in the art to which the present invention belongs. By way of further guidance, definitions of terms are included to better appreciate the teachings of the present invention.

[0024] In the following passages, different aspects of the invention are defined in more detail. Each aspect thus defined may be combined with any other aspect, unless expressly stated to the contrary. In particular, any feature indicated as being preferred or advantageous may be combined with any other feature indicated as being preferred or advantageous.

[0025] References throughout this specification to "one embodiment" or "embodiment" mean that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, the appearances of the phrases "in one embodiment" or "in an embodiment" in various places throughout this specification may, but do not necessarily all refer to the same embodiment. Furthermore, particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments, as would be apparent to one of ordinary skill in the art from this disclosure. Furthermore, while some embodiments described herein include some features but not other features included in other embodiments, combinations of features of different embodiments are meant to be within the scope of the present invention and form different embodiments, as would be understood by one of ordinary skill in the art.

[0026] The terms "comprising", "including" and "consisting of", as used herein, are synonymous with "including", "including" or "containing", "containing" and are inclusive or expansive and do not exclude further, unrecited members, elements or method steps. It should be recognized that the terms "comprising", "including" and "consisting of", as used herein, include the terms "comprising", "consists of" and "consisting of".

[0027] As used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. By way of example, "a step" means one step or multiple steps.

[0028] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. All publications referenced herein are incorporated by reference thereto.

[0029] The recitation of numerical ranges by endpoints includes all integers and, where appropriate, fractions subsumed within the range (e.g., 1 to 5 can include 1, 2, 3, 4, e.g., when referring to several elements, and can also include 1.5, 2, 2.75, and 3.80, e.g., when referring to measurements). The recitation of endpoints also includes the endpoint values ​​themselves (e.g., 1.0 to 5.0 includes both 1.0 and 5.0). Any numerical range recited herein is intended to include all subranges subsumed therein.

[0030] The term "about," as used herein, when referring to a measurable value, e.g., a parameter, amount, temporal duration, etc., is meant to encompass variations of the specified value and of + / - 10% or less, preferably + / - 5% or less, more preferably + / - 1% or less from the specified value, insofar as such variations are appropriate to be made in the disclosed invention. It should be understood that the value to which the modifier "about" refers is itself also specifically, and preferably, disclosed.

[0031] Whenever the term "substituted" is used in the present invention, it is meant to indicate that one or more hydrogens on the atom indicated in the expression using "substituted" are replaced with one selected from the indicated group, provided that the normal valence of the indicated atom is not exceeded, and the substitution results in a chemically stable compound. When a group can be substituted, such a group may be substituted with one or more, preferably 1, 2 or 3, substituents.

[0032] The above terms and other terms used herein are well understood by those of skill in the art.

[0033] Preferred descriptions (features) and embodiments of the methods, formulations and uses of the present invention are described herein below. Each description and embodiment of the present invention thus defined may be combined with any other description and / or embodiment, unless clearly stated to the contrary. In particular, any feature indicated as being preferred or advantageous may be combined with any other feature or description indicated as being preferred or advantageous. Here, the present invention is particularly captured by any one or any combination of one or more of the following numbered descriptions and embodiments, together with any other aspects and / or embodiments.

[0034] 1. A method for polymerizing lactide, comprising the steps of: a) preparing a liquid catalyst formulation comprising a catalyst, an initiator and a lactide; b) contacting lactide with the liquid catalyst formulation prepared in step a) and polymerizing said lactide in the presence of said liquid catalyst formulation to form polylactide; A method comprising:

[0035] 2. A method for polymerizing lactide, comprising the steps of: a) preparing a liquid catalyst formulation comprising a catalyst, an initiator and a lactide, the catalyst being applied in solid form to produce a formulation; b) contacting lactide with the liquid catalyst formulation prepared in step a) and polymerizing said lactide in the presence of said liquid catalyst formulation to form polylactide; A method comprising:

[0036] 3. A method for polymerizing lactide, comprising the steps of: a) preparing a liquid catalyst formulation comprising a catalyst, an initiator and a lactide; b) contacting lactide with the liquid catalyst formulation prepared in step a) and polymerizing said lactide in the presence of said liquid catalyst formulation to form polylactide; Including, A process wherein the catalyst applied in step a) is a metal coordination compound, wherein the metal is from Group IV, preferably at least one of Zr or Hf.

[0037] 4. A method for polymerizing lactide, comprising the steps of: a) preparing a liquid catalyst formulation comprising a catalyst, an initiator and a lactide; b) contacting lactide with the liquid catalyst formulation prepared in step a) and polymerizing said lactide in the presence of said liquid catalyst formulation to form polylactide; Including, wherein the catalyst is a metal coordination compound; wherein the metal is at least one of Zr or Hf; wherein the parent ligand of said compound is of formula (I) [ka] Wherein R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 is halogen, hydroxyl, C 1~10 Alkyl, haloC 1~10 Alkyl, C 1~10 Alkoxy and HaloC 1~10 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, H, halogen, -NO 2 and C 1~10 wherein each of the hydrocarbyl groups is independently selected from the group consisting of:

[0038] 5. The method of any of statements 1 to 4, wherein the molar ratio of lactide to catalyst in the blend is comprised between 50:1 and 500:1, preferably between 100:1 and 250:1, such as 100:1; 125:1; 145:1; 150:1; 155:1; 175:1; 190:1; or 200:1.

[0039] 6. The method of any of statements 1 to 5, wherein the molar ratio of initiator to catalyst in the formulation is comprised between 50:1 and 500:1, preferably between 100:1 and 250:1, for example, 100:1; 125:1; 145:1; 150:1; 155:1; 175:1; 190:1; or 200:1.

[0040] 7. The method of any of statements 1-6, wherein the molar ratio of lactide to initiator in the formulation is 1:1.

[0041] 8. The method of any of statements 1-7, wherein the liquid catalyst formulation is prepared by mixing a catalyst, an initiator and a lactide to form a slurry, and heating the slurry to a temperature of 150-200°C, e.g., 170-190°C, to obtain a liquid formulation.

[0042] 9. The method of any of statements 1 to 8, wherein the slurry is heated for 10 to 120 minutes, preferably 30 to 60 minutes, to obtain a liquid formulation.

[0043] 10. The method of any of statements 1-9, wherein the liquid catalyst formulation is prepared in step a) by mixing a catalyst provided in solid form with an initiator and a lactide.

[0044] 11. The method of any one of statements 1 to 10, wherein the catalyst is a metal coordination compound.

[0045] 12. The method of any of statements 1 to 11, wherein the catalyst is a metal coordination compound and the metal is at least one of Zr or Hf.

[0046] 13. The catalyst is a metal coordination compound; wherein the metal is at least one of Zr or Hf; wherein the parent ligand of said compound is of formula (I) [ka] Wherein R 1 , R2 , R 3 , R 4 , R 5 , and R 6 is halogen, hydroxyl, C 1~10 Alkyl, haloC 1~10 Alkyl, C 1~10 Alkoxy and HaloC 1~10 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, H, halogen, -NO 2 and C 1~10 13. The method of any of statements 1 to 12, wherein each of the hydrocarbyl groups is independently selected from the group consisting of:

[0047] 14. The method of any one of statements 3 to 13, wherein the metal is Zr.

[0048] 15.R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 is optionally substituted with one or more substituents each independently selected from halogen or hydroxyl; 2 and C 1~10 15. The method of any of statements 4 to 14, wherein each of the groups is independently selected from the group consisting of alkyl.

[0049] 16.R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 But, C 1~10 From alkyl, preferably C 1~4 16. The method of any of statements 4 to 15, wherein each of the groups is independently selected from alkyl.

[0050] 17.R 1 , R 2 , R 3 , R 4 , R 5 , and R 617. The method according to any of statements 4 to 16, wherein are the same and are t-butyl or methyl, preferably methyl.

[0051] 18. The method of any one of statements 1 to 17, wherein the initiator is an alcohol.

[0052] 19. The method of any of statements 1 to 18, wherein the initiator is an alcohol selected from the group consisting of benzyl alcohol, 1-hexanol, isopropanol, 2-ethylhexanol and 1-dodecanol, more preferably benzyl alcohol.

[0053] 20. The method of any of statements 1-19, wherein the molar ratio of lactide to catalyst provided in step b) is in the range of 100,000:1 to 1,000:1, preferably 80,000:1 to 2,000:1, or preferably 60,000:1 to 5,000:1.

[0054] 21. The method of any of statements 1-20, wherein the molar ratio of lactide to initiator provided in step b) is in the range of 1500:1 to 2.5:1, preferably 800:1 to 50:1, or preferably 750:1 to 50:1.

[0055] 22. The method of any of statements 1 to 21, wherein the catalyst concentration in the method, calculated as metal weight, is in the range of 1 ppm to 500 ppm, preferably 2 ppm to 200 ppm, or preferably 5 ppm to 50 ppm, or preferably 8 ppm to 25 ppm.

[0056] 23. The method of any of statements 1-22, wherein a liquid catalyst formulation is contacted with the molten lactide in step b).

[0057] 24. The method of any of statements 1 to 23, wherein the lactide is polymerized in the presence of the liquid catalyst formulation at a temperature of at least 100°C, preferably at least 130°C, preferably comprised between 130 and 240°C, more preferably comprised between 140 and 220°C.

[0058] 25. The method of any of statements 1-24, wherein the polymerization is carried out in step b) in the absence of extraneous solvent.

[0059] 26. The method of any of statements 1-25, wherein the polymerization is carried out in step b) in the absence of an exogenous initiator.

[0060] 27. The method of any of statements 1-26, wherein additional exogenous initiator is added during polymerization in step b).

[0061] 28. The method of any of statements 1-27, wherein the lactide applied to prepare the liquid catalyst formulation in step a) is the same as the lactide applied in step b).

[0062] 29. The method of any of statements 1-27, wherein the lactide applied to prepare the liquid catalyst formulation in step a) is different from the lactide applied in step b).

[0063] 30. A liquid catalyst formulation comprising a catalyst, an initiator and a lactide, wherein the formulation is described in any of statements 1 to 19.

[0064] 31. Use of a liquid catalyst formulation according to statement 30 for polymerizing lactide.

[0065] 32. The use according to statement 31, wherein the blend is applied in a molar ratio of catalyst to lactide comprised between 100,000:1 and 1,000:1, preferably between 80,000:1 and 2,000:1, or preferably between 60,000:1 and 5,000:1.

[0066] 33. A polylactide obtained or obtainable by a method according to any of statements 1 to 29.

[0067] The present invention is based on the surprising discovery that a catalyst system formulated as a solution can be efficiently used in the polymerization of lactide. More particularly, the present invention is based on the use of a liquid catalyst formulation, in which a certain amount of lactide is "pre-reacted" or "pre-polymerized" or "pre-contacted" with a well-defined molar ratio of catalyst and initiator. In a liquid catalyst formulation as defined in the present invention, a solid catalyst is reactively solubilized by reacting the solid catalyst with an initial amount of lactide and initiator. The inventors have shown that when this liquid catalyst formulation is contacted with molten lactide under industrially relevant polymerization conditions, such a liquid catalyst formulation achieves extremely fast and predictable kinetics with no catalyst induction period at significantly low metal concentrations, resulting in a polylactide with well-defined properties. According to the present invention, a polymerization process is provided that advantageously allows for the use of an insoluble polymerization catalyst in the preparation of polylactide. According to the present invention, a polymerization process is provided that advantageously allows for the use of a polymerization catalyst provided in solid form.

[0068] The present invention relates to a process for preparing polylactide by catalytic polymerization of lactide monomer. The terms "polylactide", "PLA" and "polylactic acid" are used synonymously herein.

[0069] The present invention relates to a) preparing a liquid catalyst formulation comprising a catalyst, an initiator and a lactide; b) contacting lactide with the liquid catalyst formulation prepared in step a) and polymerizing said lactide in the presence of said liquid catalyst formulation to form polylactide; The present invention provides a method for polymerizing lactide, comprising:

[0070] In certain embodiments, the present invention provides a) preparing a liquid catalyst formulation comprising a catalyst, an initiator and a lactide, the catalyst being applied in solid form to produce a formulation; b) contacting lactide with the liquid catalyst formulation prepared in step a) and polymerizing said lactide in the presence of said liquid catalyst formulation to form polylactide; The present invention provides a method for polymerizing lactide, comprising:

[0071] Thus, the method of polymerizing lactide according to the present invention comprises two main steps carried out in the following order: First, a liquid catalyst formulation comprising a catalyst, an initiator and lactide as defined herein is prepared separately. Then, second, this liquid catalyst formulation is added to lactide (monomer) for its polymerization in the presence of the formulation. In other words, step a) is carried out before step b). The liquid catalyst formulation prepared in step a) is stable at ambient temperature (e.g., 25° C.) and therefore can be easily prepared and stored before use in the polymerization reaction of lactide.

[0072] The first step in the method according to the present invention is therefore the preparation of a liquid catalyst formulation.As used herein, the term "formulation" is used as a synonym for "composition".The term "liquid catalyst formulation" or "liquid catalyst composition" as used herein refers to a liquid composition, i.e., a solution, in which its components, i.e., catalyst, initiator and lactide, are in solubilized form.The liquid catalyst formulation and its components are described in detail below.

[0073] In the second step of the process according to the invention, the liquid catalyst formulation is contacted with lactide (lactide monomer) for its polymerization to form polylactide. The term "contacting" is used herein as a synonym for "adding" or "combining" or "feeding" or "mixing" or "replenishing" and is intended to refer to the addition of the formulation as defined herein to lactide for the latter's polymerization.

[0074] It is noted that lactide can exist in three different geometric structures with diastereomeric relationships. Lactide as used in the method of the present invention can be L-lactide (derived from two L-lactic acid molecules), D-lactide (derived from two D-lactic acid molecules), meso-lactide (derived from an L-lactic acid molecule and a D-lactic acid molecule), or a mixture of two or more of the above. A 50 / 50 mixture of L-lactide and D-lactide, having a melting point of about 126°C, is often referred to in the literature as D,L-lactide or racemic lactide (also referred to herein as "rac-lactide" or "racemic lactide" or "rac-lactide"). Mixtures of the above lactides are also suitable for use in this method.

[0075] In some embodiments, the lactide used as the starting material is L-lactide with up to 50% by weight of other lactides. For example, the lactide used as the starting material can be L-lactide containing 50-10% D-lactide. In other embodiments, the lactide is substantially pure L-lactide, where the term substantially pure means that it may contain up to 10% by weight of other lactides, e.g., up to 5% by weight, or up to 1% by weight. In another embodiment, the lactide is substantially pure D-lactide, where the term substantially pure means that it may contain up to 10% by weight of other lactides, e.g., up to 5% by weight, or up to 1% by weight.

[0076] In certain embodiments of the present invention, the lactide applied to prepare the liquid catalyst formulation in step a) of the method is the same as the lactide applied in polymerization step b) of the method as provided herein. In certain other embodiments of the present invention, the lactide applied to prepare the liquid catalyst formulation in step a) of the method is not the same as the lactide applied in polymerization step b) of the method as provided herein.

[0077] In one embodiment, the liquid catalyst formulation is contacted with the lactide that is in a molten state. In another embodiment, the liquid catalyst formulation is contacted with a solid lactide in step b).

[0078] Lactide is polymerized in the presence of said liquid catalyst formulation at a temperature of at least 100° C., preferably at least 130° C. For example, lactide is polymerized in the presence of said liquid catalyst formulation at a temperature comprised between 130 and 240° C., or more preferably between 140 and 220° C. Preferably, no solvent is added during this polymerization step. In other words, the polymerization is carried out in the absence of extraneous solvent in step b).

[0079] An additional exogenous initiator may be added during the polymerization reaction in step b), but it is not necessary to add it in addition to the initiator already provided by step a). In other words, the polymerization can be advantageously carried out in step b) in the absence of an exogenous initiator. The role of initiator (nucleophile) in the polymerization of lactide is already played by the solvent phase of the liquid catalyst formulation, thus eliminating the need for a separate additional initiator to be introduced into the polymerization process. However, the method also allows the addition of an additional exogenous initiator during the polymerization reaction in step b).

[0080] In certain embodiments of the present invention, the polymerization of lactide in the presence of a liquid catalyst formulation as defined herein can also be carried out in the presence of other monomers different from lactide monomer, such as related cyclic esters, such as glycolide. Another useful reactive monomer that can be added during the polymerization step is, for example, caprolactone. Valuable copolymers for different applications can thus be produced when using these or related reactants together with lactide.

[0081] The liquid catalyst formulation as provided herein comprises, and preferably consists of, a catalyst, an initiator, and a lactide. In particular, a liquid catalyst formulation is provided, in which these three components are provided in well-defined amounts and molar ratios.

[0082] In one embodiment, the molar ratio of lactide to catalyst in the blend is comprised between 50:1 and 500:1, and preferably between 100:1 and 250:1, all individual values ​​and subranges from 50:1 to 500:1 are included herein and disclosed herein. For example, the molar ratio of lactide to catalyst in the blend can be from a lower limit of 50:1; 60:1; 70:1; 80:1; 90:1; 100:1; 110:1; 120:1; 130:1; 140:1; 145:1; 150:1; 155:1; 160:1; 165:1 to an upper limit of 170:1; 175:1; 180:1; 185:1; 190:1; 195:1; 200:1; 210:1; 220:1; 230:1; 240:1; 250:1; 275:1; 300:1; 350:1; 400:1; 450:1; 500:1. Examples of suitable molar ratios of lactide to catalyst in the blend include, but are not limited to, for example, about 100:1; about 125:1; about 145:1; about 150:1; about 155:1; about 175:1; about 190:1; or about 200:1.

[0083] In one embodiment, suitable molar ratios of lactide to catalyst in the blend include, but are not limited to, for example, (100:1) + / - 10%; preferably, (100:1) + / - 5%; more preferably, (100:1) + / - 1%. In one embodiment, suitable molar ratios of lactide to catalyst in the blend include, but are not limited to, for example, (125:1) + / - 10%; preferably, (125:1) + / - 5%; more preferably, (125:1) + / - 1%. In one embodiment, suitable molar ratios of lactide to catalyst in the blend include, but are not limited to, for example, (145:1) + / - 10%; preferably, (145:1) + / - 5%; more preferably, (145:1) + / - 1%. In one embodiment, suitable molar ratios of lactide to catalyst in the blend include, but are not limited to, for example, (150:1) + / - 10%; preferably, (150:1) + / - 5%; more preferably, (150:1) + / - 1%. In one embodiment, suitable molar ratios of lactide to catalyst in the blend include, but are not limited to, for example, (155:1) + / - 10%; preferably, (155:1) + / - 5%; more preferably, (155:1) + / - 1%. In one embodiment, suitable molar ratios of lactide to catalyst in the blend include, but are not limited to, for example, (175:1) + / - 10%; preferably, (175:1) + / - 5%; more preferably, (175:1) + / - 1%. In one embodiment, suitable molar ratios of lactide to catalyst in the blend include, but are not limited to, for example, (190:1) + / - 10%, preferably, (190:1) + / - 5%, more preferably, (190:1) + / - 1%. In one embodiment, suitable molar ratios of lactide to catalyst in the blend include, but are not limited to, for example, (200:1) + / - 10%, preferably, (200:1) + / - 5%, more preferably, (200:1) + / - 1%.

[0084] In one embodiment, examples of suitable molar ratios of lactide to catalyst in the formulation include, but are not limited to, for example, 100:1; 125:1; 145:1; 150:1; 155:1; 175:1; 190:1, or 200:1.

[0085] In another embodiment, the molar ratio of initiator to catalyst in the formulation is comprised between 50:1 and 500:1, and preferably between 100:1 and 250:1. All individual values ​​and subranges from 50:1 to 500:1 are included herein and disclosed herein; for example, the molar ratio of initiator to catalyst in the formulation can be from a lower limit of 50:1; 60:1; 70:1; 80:1; 90:1; 100:1; 110:1; 120:1; 130:1; 140:1; 145:1; 150:1; 155:1; 160:1; 165:1 to an upper limit of 170:1; 175:1; 180:1; 185:1; 190:1; 195:1; 200:1; 210:1; 220:1; 230:1; 240:1; 250:1; 275:1; 300:1; 350:1; 400:1; 450:1; 500:1.

[0086] Examples of suitable molar ratios of initiator to catalyst in the formulation include, but are not limited to, for example, about 100:1; about 125:1; about 145:1; about 150:1; about 155:1; about 175:1; about 190:1; or about 200:1.

[0087] In one embodiment, suitable molar ratios of initiator to catalyst in the formulation include, but are not limited to, for example, (100:1) + / - 10%; preferably, (100:1) + / - 5%; more preferably, (100:1) + / - 1%. In one embodiment, suitable molar ratios of initiator to catalyst in the formulation include, but are not limited to, for example, (125:1) + / - 10%; preferably, (125:1) + / - 5%; more preferably, (125:1) + / - 1%. In one embodiment, suitable molar ratios of initiator to catalyst in the formulation include, but are not limited to, for example, (145:1) + / - 10%; preferably, (145:1) + / - 5%; more preferably, (145:1) + / - 1%. In one embodiment, suitable molar ratios of initiator to catalyst in the formulation include, but are not limited to, for example, (150:1) + / - 10%; preferably, (150:1) + / - 5%; more preferably, (150:1) + / - 1%. In one embodiment, suitable molar ratios of initiator to catalyst in the formulation include, but are not limited to, for example, (155:1) + / - 10%; preferably, (155:1) + / - 5%; more preferably, (155:1) + / - 1%. In one embodiment, suitable molar ratios of initiator to catalyst in the formulation include, but are not limited to, for example, (175:1) + / - 10%; preferably, (175:1) + / - 5%; more preferably, (175:1) + / - 1%. In one embodiment, suitable molar ratios of initiator to catalyst in the formulation include, but are not limited to, for example, (190:1) + / - 10%, preferably, (190:1) + / - 5%, more preferably, (190:1) + / - 1%. In one embodiment, suitable molar ratios of initiator to catalyst in the formulation include, but are not limited to, for example, (200:1) + / - 10%, preferably, (200:1) + / - 5%, more preferably, (200:1) + / - 1%.

[0088] In one embodiment, examples of suitable molar ratios of initiator to catalyst in the formulation include, but are not limited to, for example, 100:1; 125:1; 145:1; 150:1; 155:1; 175:1; 190:1, or 200:1.

[0089] In another embodiment, the molar ratio of lactide to initiator in the formulation is about 1:1, such as (1:1) + / - 10%, or such as (1:1) + / - 5%, or such as (1:1) + / - 1%, or such as 1:1. Preferably, lactide and initiator are applied in equimolar amounts in the formulation.

[0090] In one example, a liquid catalyst formulation is provided, wherein the molar ratio of lactide to catalyst is about 200:1; the molar ratio of initiator to catalyst is about 200:1, and the molar ratio of lactide to initiator is about 1:1. In one example, a liquid catalyst formulation is provided, wherein the molar ratio of lactide to catalyst is (200:1) + / - 10%, preferably (200:1) + / - 5%, more preferably (200:1) + / - 1%; the molar ratio of initiator to catalyst is (200:1) + / - 10%, preferably (200:1) + / - 5%, more preferably (200:1) + / - 1%; the molar ratio of lactide to initiator is (1:1) + / - 10%, preferably (1:1) + / - 5%, more preferably (1:1) + / - 1%. In one example, a liquid catalyst formulation is provided, wherein the molar ratio of lactide to catalyst is 200:1; the molar ratio of initiator to catalyst is 200:1, and the molar ratio of lactide to initiator is 1:1.

[0091] In another example, a liquid catalyst formulation is provided, wherein the molar ratio of lactide to catalyst is about 150:1; the molar ratio of initiator to catalyst is about 150:1, and the molar ratio of lactide to initiator is about 1:1. In one example, a liquid catalyst formulation is provided, wherein the molar ratio of lactide to catalyst is (150:1) + / - 10%, preferably (150:1) + / - 5%, more preferably (150:1) + / - 1%, the molar ratio of initiator to catalyst is (150:1) + / - 10%, preferably (150:1) + / - 5%, more preferably (150:1) + / - 1%, and the molar ratio of lactide to initiator is (1:1) + / - 10%, preferably (1:1) + / - 5%, more preferably (1:1) + / - 1%. In another example, a liquid catalyst formulation is provided, wherein the molar ratio of lactide to catalyst is 150:1; the molar ratio of initiator to catalyst is 150:1, and the molar ratio of lactide to initiator is 1:1.

[0092] In another example, a liquid catalyst formulation is provided, wherein the molar ratio of lactide to catalyst is about 100:1; the molar ratio of initiator to catalyst is about 100:1, and the molar ratio of lactide to initiator is about 1:1. In one example, a liquid catalyst formulation is provided, wherein the molar ratio of lactide to catalyst is (100:1) + / - 10%, preferably (100:1) + / - 5%, more preferably (100:1) + / - 1%; the molar ratio of initiator to catalyst is (100:1) + / - 10%, preferably (100:1) + / - 5%, more preferably (100:1) + / - 1%; the molar ratio of lactide to initiator is (1:1) + / - 10%, preferably (1:1) + / - 5%, more preferably (1:1) + / - 1%. In another example, a liquid catalyst formulation is provided, wherein the molar ratio of lactide to catalyst is 100:1; the molar ratio of initiator to catalyst is 100:1, and the molar ratio of lactide to initiator is 1:1.

[0093] The liquid catalyst formulation of the present invention may be advantageously prepared by mixing a catalyst, an initiator and a lactide as defined herein to form a slurry. The slurry is then heated to obtain the formulation. The slurry is heated for 10-120 minutes, such as 30-60 minutes, such as at least 20 minutes, at least 35 minutes, at least 40 minutes, at least 45 minutes, or at least 50 minutes to obtain the liquid formulation. The slurry may be heated to a temperature of 150-200°C, such as 170-190°C, for example at 175°C or 180°C, to obtain the liquid formulation.

[0094] The catalyst contained in the liquid catalyst formulation is a catalyst suitable for the polymerization of lactide. The terms "catalyst" or "catalyst compound" are used interchangeably herein.

[0095] In one embodiment, such catalysts are metal coordination compounds or metal coordination complexes or metal-ligand coordination compounds. The terms "metal coordination complex" or "metal coordination compound" or "metal-ligand coordination compound" are used interchangeably herein and all refer to compounds that consist of a central metal ion and one or more surrounding bound ligands.

[0096] In certain embodiments, a) preparing a liquid catalyst formulation comprising a catalyst, an initiator and a lactide; b) contacting lactide with the liquid catalyst formulation prepared in step a) and polymerizing said lactide in the presence of said liquid catalyst formulation to form polylactide; The present invention provides a method for polymerizing lactide, comprising: Here, the catalyst applied in step a) is a metal coordination compound, where the metal is from group IV, preferably at least one of Zr or Hf.

[0097] In a preferred embodiment, the catalyst applied herein is a metal coordination compound, wherein the metal is at least one of Zr or Hf; wherein the parent ligand of said compound is of formula (I) [ka] Wherein R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 is halogen, hydroxyl, C 1~10 Alkyl, haloC 1~10 Alkyl, C 1~10 Alkoxy and HaloC 1~10 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, H, halogen, -NO 2 and C 1~10 are each independently selected from the group consisting of hydrocarbyl groups.

[0098] In certain embodiments, a) preparing a liquid catalyst formulation comprising a catalyst, an initiator and a lactide; b) contacting lactide with the liquid catalyst formulation prepared in step a) and polymerizing said lactide in the presence of said liquid catalyst formulation to form polylactide; The present invention provides a method for polymerizing lactide, comprising: wherein the catalyst is a metal coordination compound; wherein the metal is at least one of Zr or Hf; wherein the parent ligand of said compound is of formula (I) [ka] Wherein R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 is halogen, hydroxyl, C 1~10 Alkyl, haloC 1~10 Alkyl, C 1~10 Alkoxy and HaloC 1~10Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, H, halogen, -NO 2 and C 1~10 are each independently selected from the group consisting of hydrocarbyl groups.

[0099] Each of Zr and Hf is bound as a metal ion in the metal coordination compound. It is noted that in metal-ligand coordination compounds, the ligand is anionic, i.e., negatively charged and lacks a proton on the hydroxyl group. For that reason, the ligand in the formula is designated as the "parent" ligand.

[0100] The term "hydrocarbyl" or "C 1~10 Hydrocarbyl" or "C 1~10 A "hydrocarbyl group," as used herein, is a group consisting of 1 ~C 10 It refers to normal, secondary, tertiary, unsaturated or saturated, non-aromatic, acyclic or cyclic hydrocarbons and combinations thereof. Thus, the term includes alkyl, alkenyl, and alkynyl, e.g., C 1~10 Alkyl and C 2~10 It may contain alkenyl.

[0101] The term “C 1~10 "Alkyl" means, as a group or part of a group, a group of formula C n H 2n+1 where n is a number ranging from 1 to 10. The alkyl group may be linear or branched and may be substituted as provided herein. Preferably, the alkyl group contains 1 to 6 carbon atoms, preferably 1 to 5 carbon atoms, preferably 1 to 4 carbon atoms, preferably 1 to 3 carbon atoms. When a subscript is used herein following a carbon atom, the subscript refers to the number of carbon atoms that the named group may contain. For example, the term "C 1~6 "Alkyl" means, as a group or part of a group, a group of formula C n H 2n+1 where n is a number ranging from 1 to 6. For example, C1~6 Alkyl includes all straight or branched alkyl groups having 1 to 6 carbon atoms, and thus includes, for example, methyl, ethyl, n-propyl, i-propyl, 2-methyl-ethyl, butyl and its isomers (e.g., n-butyl, i-butyl and t-butyl); pentyl and its isomers, hexyl and its isomers, etc. For example, C 1~4 Alkyl includes all linear or branched alkyl groups having 1 to 4 carbon atoms and thus includes, for example, methyl, ethyl, n-propyl, i-propyl, 2-methyl-ethyl, butyl and its isomers such as n-butyl, i-butyl and t-butyl. Preferred alkyl is methyl or butyl and its isomers n-butyl, i-butyl and t-butyl.

[0102] The term "alkenyl" or "C 2~10 "Alkenyl," as used herein, refers to an alkyl group having at least one site of unsaturation, i.e., at least one (usually one to three, preferably one) of a carbon-carbon, sp2 double bond. 2 ~C 10 It can be normal, secondary or tertiary, straight chain or cyclic, branched or linear hydrocarbon. Examples include, but are not limited to, ethylene or vinyl (-CH=CH 2 ), allyl (-CH 2 CH=CH 2 ), cyclopentenyl (-C 5 H 7 ), and cyclohexenyl (-C 6 H 9 The double bond may be in a cis or trans configuration. In certain embodiments, the term alkenyl refers to a C 2~8 Hydrocarbons, and more particularly, C 2~6 The preferred alkenyl is C 2~4 It is alkenyl.

[0103] As used herein, and unless otherwise stated, the term "alkoxy" as a group or part of a group refers to a substituent in which an alkyl group is attached to an oxygen atom through a single bond, such as, but not limited to, methoxy, ethoxy, propoxy, butoxy. Preferred alkoxy are 1~4 It is an alkoxy.

[0104] The terms "halogen" or "halo" as a group or part of a group are generic to fluoro, chloro, bromo, or iodo.

[0105] The terms "hydroxyl" or "hydroxy" as used herein refer to the group --OH.

[0106] As used herein, the term "aryl" as a group or part of a group refers to an aromatic hydrocarbon group of 6 to 30 carbon atoms obtained by removal of hydrogen from a carbon atom of a parent aromatic ring system. Typical aryl groups include, but are not limited to, one ring, or two or three rings fused together, groups derived from benzene, naphthalene, anthracene, biphenyl, and the like. The term "parent aromatic ring system" refers to a monocyclic aromatic ring system or a bicyclic or tricyclic ring system, of which at least one ring is aromatic. Thus, in this embodiment, typical aryl groups include, but are not limited to, one ring, or two or three rings fused together, groups derived from benzene, naphthalene, anthracene, biphenyl, 2,3-dihydro-1H-indenyl, 5,6,7,8-tetrahydronaphthalenyl, 1,2,6,7,8,8a-hexahydroacenaphthylenyl, 1,2-dihydroacenaphthylenyl, and the like. Particular aryl groups are phenyl and naphthyl, especially phenyl.

[0107] The term "arylalkyl" or "arylalkyl", as used herein, refers to an acyclic alkyl group in which one of the hydrogen atoms bonded to a carbon atom, typically a terminal or sp3 carbon atom, is replaced with an aryl group. Typical arylalkyl groups include, but are not limited to, benzyl, 2-phenylethan-1-yl, 2-phenylethen-1-yl, naphthylmethyl, 2-naphthylethyl, and the like. An arylalkyl group contains 6 to 20 carbon atoms, e.g., the alkyl portion of the arylalkyl group is 1 to 6 carbon atoms and the aryl portion is 5 to 14 carbon atoms.

[0108] In a preferred embodiment, a catalyst is provided wherein the metal is Zr. In another preferred embodiment, a catalyst is provided wherein the metal is Hf.

[0109] In one embodiment, a catalyst is provided, wherein R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 is optionally substituted with one or more substituents each independently selected from halogen or hydroxyl; 2 and C 1~10 alkyl.

[0110] In one embodiment, a catalyst is provided, wherein R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 is C 1~10 Alkyl, preferably C 1~6 Alkyl, more preferably C 1~4 alkyl.

[0111] In one embodiment, a catalyst is provided, wherein R 1 , R 2 , R 3 , R 4, R 5 , and R 6 are the same and are optionally substituted with one or more substituents each independently selected from halogen or hydroxyl; 2 and C 1~10 alkyl.

[0112] In one embodiment, a catalyst is provided, wherein R 1 and R 2 are identical. In one embodiment, a catalyst is provided, wherein R 3 and R 4 are identical. In one embodiment, a catalyst is provided, wherein R 5 and R 6 are identical. In one embodiment, a catalyst is provided, wherein R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are identical.

[0113] In one embodiment, a catalyst is provided, wherein R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are the same, and C 1~10 Alkyl, preferably C 1~6 Alkyl, more preferably C 1~4 is selected from alkyl.

[0114] In one embodiment, a catalyst is provided, wherein R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are the same and are t-butyl or methyl, preferably methyl.

[0115] Examples of suitable ligands include, for example, tris-(-3.5-ditert-butyl-2-hydroxybenzyl)amine and tris-(-3.5-dimethyl-2-hydroxybenzyl)amine.

[0116] Specific examples of suitable catalysts according to the present invention include, for example, those of formula (II) [ka] It is represented by:

[0117] In this particular embodiment, one metal center is coordinated with two ligands. This results in the formation of a so-called zwitterionic structure. The zwitterionic structure, in which one metal center is complexed with two ligands, does not contain a polymerization initiator group per se. Rather, the complex is expected to form a more active species at higher temperatures, which forms the actual catalytic center. Metal-ligand coordination compounds with this type of ligand are particularly interesting in the context of the present invention, considering their simple and straightforward preparation and the stability of the compounds under storage conditions.

[0118] The liquid catalyst formulation comprises an initiator. The terms "initiator" or "co-initiator" are used interchangeably herein. In the context of the present invention, this compound increases the polymerization rate of the reaction and provides control over the molecular weight of the resulting polymerization product. According to the present method, the initiator is added to the liquid catalyst formulation. Optionally, an additional exogenous initiator may also be added to the reaction mixture during the polymerization step b).

[0119] Suitable initiators for use in the liquid catalyst formulations according to the present invention may include alcohols.

[0120] In a preferred embodiment, the initiator has the formula R 7 —OH, where R 7 is halogen, hydroxyl and C 1~6 C is optionally substituted with one or more substituents selected from the group consisting of alkyl, 1~20 Alkyl, C 6~30Aryl and C 6~30 Aryl C 1~20 Preferably, R is selected from the group consisting of alkyl. 7 is halogen, hydroxyl, and C 1~6 C is optionally substituted with one or more substituents each independently selected from the group consisting of alkyl, 3~12 Alkyl, C 6~10 Aryl and C 6~10 Aryl C 1~12 alkyl; preferably, R 7 is halogen, hydroxyl and C 1~4 C is optionally substituted with one or more substituents each independently selected from the group consisting of alkyl, 3~12 Alkyl, C 6~10 Aryl and C 6~10 Aryl C 1~12 The co-initiator may be a monoalcohol. The alcohol may be a polyol, such as a diol, triol or a polyhydric alcohol of higher functionality. The alcohol may be derived from biomass, such as glycerol or propanediol or any other sugar-based alcohol, such as erythritol. The alcohol may be used alone or in combination with another alcohol. In one embodiment, non-limiting examples of co-initiators include benzyl alcohol, 1-octanol, 1-decanol, isopropanol, propanediol, trimethylolpropane, 2-butanol, 3-buten-2-ol, 1,3-butanediol, 1,4-butanediol, 1,6-hexanediol, 1,7-heptanediol, 4-bromophenol, 1,4-benzenedimethanol, and (4-trifluoromethyl)benzyl alcohol; preferably, the compound is selected from the group including benzyl alcohol, 1-hexanol, isopropanol, 2-ethylhexanol and 1-dodecanol. A particularly suitable example of a coinitiator is benzyl alcohol.

[0121] It is understood that similar coinitiators having other nucleophilic groups, such as amine groups, can also be used. Macromolecules can also be used as coinitiators, so long as they contain appropriate end groups, such as hydroxyl or amine end groups.

[0122] The inventors have surprisingly found that when using a catalyst compound in a liquid formulation as provided herein, only a trace amount of catalyst was needed to convert a very large amount of lactide. In one embodiment, a method according to the present invention is thus provided, in which the molar ratio of lactide (as provided in step b) to catalyst (a compound present in the formulation) can be from about 1,000:1 to about 100,000:1. For example, the molar ratio of lactide to catalyst can be from about 2,000:1 to about 80,000:1. For example, the molar ratio of catalyst to lactide can be from about 3,000:1 to about 75,000:1; or from about 5,000:1 to about 60,000:1. For example, the molar ratio of lactide to catalyst can be from 1,000:1 to 100,000:1; or from 2,000:1 to 80,000:1. For example, the molar ratio of the catalyst to the lactide may be from 3,000:1 to 75,000:1; or from 5,000:1 to 60,000:1.

[0123] The present invention provides a method, wherein the molar ratio of lactide to initiator provided in step b) ranges from 1.500:1 to 2.5:1, preferably from 800:1 to 50:1, or preferably from 750:1 to 50:1.

[0124] The process according to the invention is further characterized in that the amount of metals originating from the catalytic compound applied in the process is minimized. In an embodiment of the present invention, a process for polymerizing lactide is thus provided, in which the catalyst concentration in the process, calculated as metal weight, is in the range of 1 ppm to 500 ppm, preferably 2 to 200 ppm, more preferably 5 to 50 ppm, and most preferably 10 to 25 ppm. The amount of metals can be assessed by conventional analytical techniques known in the state of the art, such as, but not limited to, ICP-AES (Inductively Coupled Plasma Atomic Emission Spectroscopy).

[0125] The method makes it possible to prepare polylactides with well-defined properties.

[0126] In one embodiment, the method comprises the step of: n For example, the M of the obtained polylactide can be n For example, the M of the resulting polylactide may be in the range of about 5,000 to about 100,000 g / mol. n For example, the M of the resulting polylactide may be in the range of about 6500 to about 75000 g / mol. n may be in the range of 4000 to 200000 g / mol, for example, 5000 to 100000 g / mol or 6500 to 75000 g / mol.

[0127] In one embodiment, the method provides a dispersity (D stroke or

number

[0128] The method of the present invention allows for efficient conversion of lactide to polylactide. In one embodiment, the conversion rate can be from about 70% to about 100%; for example, the conversion rate can be from about 75% to about 99%, or from about 85% to 99%. For example, the conversion rate can be from 70% to 100%, or from 75% to 99%, or from 85% to 99%.

[0129] The invention will now be illustrated by the following non-limiting exemplification of specific embodiments of the invention. EXAMPLES

[0130] material The following chemicals were used: Lactide: L-lactide (Puralact L, ≧99% (w / w)) and D-lactide (Puralact D, ≧99% (w / w)) were obtained from Total Corbion PLA and used without further purification. Rac-lactide (50 / 50 mixture of L-lactide and D-lactide) (Sigma Aldrich, 99%), as used herein, was recrystallized three times from dry toluene and dried in vacuum.

[0131] Co-initiator: Benzyl alcohol (Sigma Aldrich, anhydrous, >99.8%) was degassed under dynamic vacuum prior to use and stored under an atmosphere of dry nitrogen.

[0132] catalyst: Stannous octoate (Sigma, 92.5-100.0%) was obtained and used as such. Toluene (Fisher, 99.8+%) was purified prior to use using an MBraun solvent purification system.

[0133] A zwitterionic zirconium compound (herein referred to as "Complex 1") was prepared as described in Example 1.

[0134] analysis Absolute molecular weight: Polymer molecular weight data were obtained using an Agilent 1260 gel permeation chromatography (GPC) system equipped with triple detection (differential refractometer, viscometer, and dual angle light scattering detector (90° / 15°, 90° data was used). A PLgel 5 μm MIXED-D 300 × 7.5 mm column was used with a PLgel 5 μm MIXED Guard 50 × 7.5 mm guard column. The mobile phase was 1 ml / min. -1 The solvent was THF at a flow rate of 1000 mL / min. The column and detector were maintained at 35° C. Data were processed using Agilent's GPC / SEC software, Revision A.02.01. Unless otherwise stated, polymer samples were not purified prior to GPC analysis.

[0135] M n,sec As used herein, is the measured Mn.

[0136] M n,theo As used herein, in the case of polymerization with the catalyst formulation according to the present invention, the following equation is used:

number

number

[0137] Dispersion is expressed by the equation

number

[0138] Conversion rate: The conversion rate was determined by determining the ratio of methine protons of PLA (5.08-5.25 ppm) and lactide monomer (5.0-5.07 ppm) using CDCl. 3 The crude product in 1Calculated from H-NMR spectra. NMR spectra are measured at 400 MHz ( 1 H), 101MHz ( 13 C) Acquired using a Bruker Avance spectrometer. 16 scans were used. 1 H spectrum was obtained. 3 was obtained from Sigma Aldrich and used as received for polymer analysis. Processing was performed using the ACD / NMR Processor Academic Edition, version 12.01.

[0139] Reaction kinetics: The reaction kinetics was monitored using in situ ATR-FTIR spectroscopic technique.

[0140] Simultaneously with the addition of the catalyst, real-time ATR-FT-IR data collection was started. Quantification of lactide and poly(lactic acid) concentrations was performed in the wavenumber region of 1203–1265 cm, respectively. -1 and 1160~1200cm -1 The COC stretching mode was achieved by integration of the ATR-FT-IR signal corresponding to the COC stretching mode at 100° C. Integration was performed between the points on the curve corresponding to the relevant wavenumbers. Further data processing and construction of semi-logarithmic plots were performed using Microsoft Excel.

[0141] The in situ ATR-FT-IR reaction monitoring instrument was calibrated using sample mixtures of PLA and rac-lactide of known molar composition in terms of the number of lactyl groups (PLA:lactide = 0:100, 20:80, 40:60, 60:40, 80:20, and 100:0, respectively). Following the acquisition of the ATR-FT-IR spectra at 174 °C corresponding to each sample, a calibration curve was constructed to describe the relationship between the integrated area of ​​the lactide signal and the concentration of lactide. Thus, the integrated area of ​​the rac-lactide signal at 174 °C (1203–1265 cm) was -1 ) and rac-lactide concentration (mol%) is [Lactide]=2.7367a+10.938 where a=lactide signal integrated area.

[0142] Following heating to 174° C. and acquisition of an ATR-FT-IR spectrum for calibration, the composition of the mixture was confirmed to be unchanged by 1H NMR spectroscopy.

[0143] TOF: The turnover frequency or TOF of a catalyst defines the number of moles of substrate that can be reacted per unit time per mole of catalyst. TOF is:

number

[0144] Example 1 : Preparation of the catalyst compound (complex 1) The zwitterionic zirconium compound of formula II, referred to herein as Complex 1, was prepared as follows. [ka]

[0145] The parent ligand of Zr coordination compound (Formula II) (see Formula I, where all R groups are methyl) was prepared by adding hexamethylenetetramine (0.94 g, 6.66 mmol) to a mixture of 2,4 disubstituted phenol (80 mmol) and paraformaldehyde (3.00 g, 100 mmol). The solution was then refluxed for 48 hours, and the white powder thus obtained was recrystallized from methanol and ether.

[0146] The Zr coordination compound was then cooled to room temperature for 2 hours in an equimolar amount of Zr(OiPr) 4 The solid zwitterionic zirconium compound, designated complex 1, was thereby recovered, which was prepared by reacting (HOiPr) with the ligand to obtain the catalyst compound after (re)crystallization.

[0147] Example 2 : Preparation of liquid catalyst formulations The following examples illustrate the preparation of three embodiments of liquid catalyst formulations according to the present invention.

[0148] In the different formulations, f1, f2 and f3, rac-lactide (see the Materials section) and benzyl alcohol were combined in equimolar amounts with 0.005, 0.0067 and 0.010 molar equivalents, respectively, of Complex 1 (also referred to as "solid zwitterionic zirconium compound" or "solid Zr compound") as prepared in Example 1 under an inert atmosphere to form a slurry.

[0149] The formulation was prepared as follows: In a glove box filled with a dry argon atmosphere, a 50 ml Schlenk flask with a J Young PTFE tap was charged with 0.347 mmol (0.32 g) of complex 1, 34.7 mmol (5 g) of rac-lactide and 34.7 mmol (3.6 ml) of benzyl alcohol, BnOH. The flask was then sealed, removed from the glove box and heated to 180° C. for 50 min with vigorous stirring in an oil bath until a clear yellow solution, formulation f1, was obtained. Formulation f1 remained liquid upon cooling to ambient temperature. Mass spectrometry revealed that the solvent phase of f1 consisted of lactyl oligomers of up to 7 lactic acid units.

[0150] Formulations f2 and f3 were prepared in a similar manner to formulation f1, whereby the amount of complex 1 used was adjusted accordingly to obtain the molar equivalents listed above.

[0151] The solvent phase of the resulting blend contains benzyl esters of oligolactides that are formed via ring-opening of lactide in the presence of stoichiometric benzyl alcohol and a subsequent transesterification event.

[0152] Table 1 summarizes the molar composition of the three liquid catalyst formulations and the heating time applied for the preparation of each formulation. The reaction schemes used to prepare the exemplary liquid catalyst formulations are depicted in FIG.

[0153] [Table 1]

[0154] Example 3 : Lactide Polymerization The following examples illustrate the polymerization of lactide by the method of the present invention in the presence of each of the formulations as disclosed in Example 2.

[0155] Polymerization of lactide was carried out in a 50 ml jacketed glass batch reactor heated by passing hot fluid through the outer jacket. Before feeding lactide to the batch reactor, the reactor was washed with dichloromethane and dried under a stream of dry air for 1 hour, during which the reactor was heated to 174° C. and then cooled to ambient temperature. To the dry reactor, 20 g of rac-lactide (see Materials section) was added. The reactor was subsequently placed under vacuum (<1 mbar) for 15 minutes. The vacuum was released by adding argon to the reactor. Two additional vacuum / argon cycles were performed on the lactide flakes in the cold reactor to ensure removal of the ambient atmosphere.

[0156] Lactide was heated to 174°C under an argon atmosphere to form a lactide melt. Once 174°C was reached, a liquid catalyst formulation was added to the reactor and polymerization of lactide proceeded. The temperature was maintained at 174°C for a defined period of time and the melt was stirred at 40 rpm. After the desired reaction time had elapsed, the resulting mixture was poured from the reactor into a beaker and cooled to ambient temperature. A sample of the resulting PLA was analyzed for molecular weight (GPC) and residual lactide monomer content ( 1 1 H NMR) was used for analysis.

[0157] Examples IE1, IE2 and IE3 represent polymerization reactions according to the invention using catalyst formulations f1, f2 and f3, respectively, as disclosed in Example 2.

[0158] CE1 represents a comparative example of lactide polymerization, in which the same catalyst is applied as in examples IE1, IE2, and IE3. In CE1, catalyst and initiator are charged individually (separately) into the reactor. Also, catalyst is applied to the reactor in solid form (powder). The same reaction conditions (20 g lactide and temperature of 174°C) are applied as in the examples according to the invention.

[0159] Table 2a summarizes the polymerization conditions, catalyst and initiator concentrations, and the resulting rate constants for the different reactions, and Table 2b summarizes the properties of the polylactides thus obtained.

[0160] TIFF0007665610000014.tif88166

[0161] TIFF0007665610000015.tif8589

[0162] The results of this example show that the liquid catalyst formulations according to the present invention can be used in the polymerization of racemic lactide. Catalyst formulations f1, f2, and f3 contain Zr coordination compounds and alcoholic initiators in various ratios (see Table 1). In each polymerization reaction, the lactide monomer:initiator ratio was 77:1 ([benzyl alcohol]=1.30 mol%). This corresponds to a polymerization yield of 11200 g mol at 100% conversion. -1 The fastest polymerization kinetics was achieved with formulation f2 (rac-LA:BnOH:catalyst compound=150:150:1).

[0163] Example 4 : Lactide Polymerization The following example illustrates the polymerization of lactide by the method of the present invention in the presence of catalyst formulation f1 as disclosed in Example 2. The polymerization reaction of racemic lactide (see the Materials section) was carried out as described in Example 3.

[0164] Examples IE1, IE4 represent polymerization reactions according to the present invention using catalyst formulation f1. CE2 and CE3 represent comparative examples of lactide polymerization, in which liquid tin octoate polymerization catalyst is applied. The same reaction conditions as in Examples IE1 and IE4 are applied. No extraneous solvent or initiator is added during polymerization reaction.

[0165] Table 3a summarizes the polymerization conditions, catalyst and initiator concentrations, and the resulting rate constants for the different reactions, and Table 3b summarizes the properties of the polylactides thus obtained.

[0166] The polymerization kinetics of the different reactions are depicted in FIG.

[0167] TIFF0007665610000016.tif98166

[0168] [Table 5]

[0169] According to the present invention, polylactides with high molar mass and low polydispersity were obtained. The experimentally obtained molar mass (M n,sec ) is the theoretically predicted molar mass (M n,theo The process according to the invention achieved high conversion of lactide in a short conversion time at significantly lower metal concentrations.

[0170] Example 5: Lactide Polymerization The following examples illustrate the polymerization of lactide by the method of the present invention in the presence of various concentrations of liquid catalyst formulations according to the present invention. The polymerization reaction of racemic lactide (see Materials) was carried out as described in Example 3. The polymerization reaction was carried out in the presence of catalyst formulation f1 as described in Example 2. As a control, the reaction was carried out in the presence of 0.25 mol% benzyl alcohol but in the absence of catalyst compound (see Controls).

[0171] Table 4a summarizes the polymerization conditions, catalyst and initiator concentrations, and the resulting rate constants for the different reactions, and Table 4b summarizes the properties of the polylactides thus obtained.

[0172] [Table 6]

[0173] TIFF0007665610000019.tif11397

[0174] From this example, it can be concluded that the reaction rate showed a linear dependence on the concentration of the catalyst formulation. Therefore, the reaction time required for high-yield polymerization at a given catalyst loading can be easily calculated. Molecular weight control was generally good, and the polydispersities recorded for the various PLA polymer products were very narrow for all PLA polymers (generally 1.07-1.1).

[0175] Example 6: Polymerization of L-lactide The following examples illustrate the polymerization of L-lactide by the method of the present invention in the presence of various liquid catalyst formulations according to the present invention. In this example, catalyst formulations prepared according to formulations f1, f2, and f3 (see Example 2) were applied to the ROP of L-lactide (see Materials section).

[0176] Ring-opening polymerization of lactide was carried out in a 2 liter batch reactor. Before feeding lactide to the batch reactor, the reactor was subjected to a vacuum of 3 mbar. The vacuum was subsequently released by adding nitrogen to the reactor. This vacuum / nitrogen cycle was carried out three times to remove residual ambient atmosphere. In a dry reactor, a specific amount of L-lactide was added to the reactor (see Table 5a). A vacuum / nitrogen cycle was subsequently carried out on the lactide flakes in the cold reactor. The reactor was then heated to 130°C. After melting the L-lactide under a nitrogen atmosphere, the catalyst formulation was added to initiate the polymerization. The temperature of the melt was increased to 180°C. The temperature was held at 180°C for the period indicated below (Table 5a) and the melt was stirred at 50 rpm. During the reaction, aliquots (approximately 10 ml) of the reaction mixture were periodically removed from the reactor and cooled on ice. These were then allowed to warm to ambient temperature. Then, 1 The mixtures were analyzed by H NMR spectroscopy (by integration of monomer and polymer methine signals) and molecular weight data were obtained by GPC. These data were used for kinetic analysis. Due to the insolubility of high molecular weight PLLA in THF, crude samples were typically diluted to 0.2 mg ml -1 and a refractive index detector calibrated against polystyrene standards was used to determine the molecular weight data with application of a Mark-Hwink value of 0.58.

[0177] The reaction process applied in IE10 was unchanged from that above, except that an additional addition of the catalyst blend was made 2 hours after injection of the blend (temperature was maintained at 180° C. throughout) and the reaction was allowed to proceed for an additional 1.5 hours. The GPC data from this reaction was bimodal, corresponding to two initiation events, indicating negligible transesterification for each addition of the blend.

[0178] For comparison, the polymerization reaction according to the present invention was carried out in a similar manner to that in which poly-L-lactide was polymerized using liquid tin octoate (Sn(Oct) 2 The procedure applied for the comparative reaction (CE5) was the same as that for the polymerization reaction formed in the presence of tin octoate (Sn(Oct)2 ) The catalyst was similar to that described for Examples IE10-IE14, with the difference that it was injected into the reactor simultaneously with the alcoholic coinitiator.

[0179] Table 5a summarizes the polymerization conditions for the different reactions, and Table 5b summarizes the properties of the poly-L-lactides thus obtained.

[0180] TIFF0007665610000020.tif95166

[0181] TIFF0007665610000021.tif125164

[0182] M n,sec Polymer molecular weight data were obtained using an Agilent 1260 gel permeation chromatography (GPC) system with a refractive index detector calibrated against 12 polystyrene standards and are reported with the application of a Mark-Hwink value of 0.58. A PLgel 5 μm MIXED-D 300 × 7.5 mm column was used with a PLgel 5 μm MIXED Guard 50 × 7.5 mm guard column. The mobile phase was 1 ml min. -1 The flow rate was THF at 35° C. The column and detector were maintained at 35° C. Data was processed using Agilent's GPC / SEC software, Revision A.02.01.

[0183] The results obtained show that in Examples IE13 and IE14, high molecular weight polylactides were produced on short time scales and in the presence of extremely low metal concentrations (0.0013-0.0019 mol%, 8-12 ppm). Furthermore, when similar metal concentrations were used, the catalyst liquid formulation according to the invention (IE11) and tin octoate, Sn(Oct) 2 Comparison of the reactions using indicated that activity was similar for the two systems.

[0184] Aliquots of the reaction mixture were removed for analysis during reactions IE10-IE14. For all Zr-catalyzed systems, the relationship between conversion and molecular weight was consistently linear, with no evidence of chain scission observed.

Claims

1. 1. A method for polymerizing lactide, comprising the steps of: a) preparing a liquid catalyst formulation comprising a catalyst, an initiator and a lactide, the liquid catalyst formulation being prepared by mixing the catalyst, the initiator and the lactide to form a slurry and heating the slurry; b) contacting the liquid catalyst formulation prepared in step a) with lactide and polymerizing the lactide in the presence of the liquid catalyst formulation to form polylactide; Including, The catalyst is a metal coordination compound, the metal is at least one of Zr or Hf; The parent ligand of said compound has the formula (I): 【Chemistry 1】 Wherein R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 is halogen, hydroxyl, C 1～10 Alkyl, haloC 1～10 Alkyl, C 1～10 Alkoxy and HaloC 1～10 Optionally substituted with one or more substituents each independently selected from the group consisting of alkoxy, H, halogen, -NO 2 and C 1～10 wherein each of the hydrocarbyl groups is independently selected from the group consisting of:

2. 2. The method of claim 1, wherein the molar ratio of lactide to catalyst in the blend is comprised between 50:1 and 500:

1.

3. The method according to claim 1 or 2, wherein the molar ratio of lactide to catalyst in the blend is comprised between 100:1 and 250:

1.

4. The process according to any one of claims 1 to 3, wherein the molar ratio of initiator to catalyst in the formulation is comprised between 50:1 and 500:

1.

5. The process according to any one of claims 1 to 4, wherein the molar ratio of initiator to catalyst in the formulation is comprised between 100:1 and 250:

1.

6. The method according to any one of claims 1 to 5, wherein the molar ratio of lactide to initiator in the formulation is 1:

1.

7. A process according to any one of claims 1 to 6, wherein the slurry is heated to a temperature comprised between 150 and 200°C to obtain a liquid catalyst formulation.

8. A process according to any one of claims 1 to 7, wherein the slurry is heated to a temperature comprised between 170 and 190°C to obtain a liquid catalyst formulation.

9. The process according to any one of claims 1 to 8, wherein the slurry is heated for 10 to 120 minutes to obtain a liquid catalyst formulation.

10. The process according to any one of claims 1 to 9, wherein the slurry is heated for 30 to 60 minutes to obtain a liquid catalyst formulation.

11. R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 is optionally substituted with one or more substituents each independently selected from halogen or hydroxyl; 2 and C 1～10 The method of any one of claims 1 to 10, wherein each of said alkyl groups is independently selected from the group consisting of alkyl.

12. The method according to any one of claims 1 to 11, wherein the initiator is an alcohol.

13. The process according to any one of claims 1 to 12, wherein the initiator is an alcohol selected from the group comprising benzyl alcohol, 1-hexanol, isopropanol, 2-ethylhexanol and 1-dodecanol.

14. The process according to any one of claims 1 to 13, wherein the initiator is benzyl alcohol.

15. The process according to any one of claims 1 to 14, wherein the molar ratio of lactide to catalyst provided in step b) is in the range of 100,000:1 to 1,000:

1.

16. 16. The process according to any one of claims 1 to 15, wherein the molar ratio of lactide to catalyst provided in step b) is in the range of 80,000:1 to 2,000:

1.

17. 17. The process according to any one of claims 1 to 16, wherein the molar ratio of lactide to catalyst provided in step b) is in the range of 60,000:1 to 5,000:

1.

18. 18. The process according to any one of the preceding claims, wherein the molar ratio of lactide to initiator provided in step b) is in the range of 1500:1 to 2.5:

1.

19. The process according to any one of claims 1 to 18, wherein the molar ratio of lactide to initiator provided in step b) is in the range of 800:1 to 50:

1.

20. The process according to any one of claims 1 to 19, wherein the molar ratio of lactide to initiator provided in step b) is in the range of 750:1 to 50:

1.

21. A process according to any one of the preceding claims, wherein the catalyst concentration in the process, calculated as weight of metal, is in the range of from 1 ppm to 500 ppm.

22. A process according to any one of the preceding claims, wherein the catalyst concentration in the process, calculated as weight of metal, is in the range of from 2 ppm to 200 ppm.

23. A process according to any one of the preceding claims, wherein the catalyst concentration in the process, calculated as weight of metal, is in the range of from 5 ppm to 50 ppm.

24. A process according to any one of the preceding claims, wherein the catalyst concentration in the process, calculated as weight of metal, is in the range of from 8 ppm to 25 ppm.

25. A process according to any one of claims 1 to 24, wherein the polymerization is carried out in step b) in the absence of extraneous solvent.

26. The method of any one of claims 1 to 25, wherein the lactide is polymerized in the presence of the liquid catalyst formulation at a temperature of at least 100°C.

27. The method of any one of claims 1 to 26, wherein the lactide is polymerized in the presence of the liquid catalyst formulation at a temperature of at least 130°C.

28. 28. The process according to any one of claims 1 to 27, wherein said lactide is polymerized in the presence of said liquid catalyst formulation at a temperature comprised between 130 and 240°C.

29. 28. The process according to any one of claims 1 to 27, wherein said lactide is polymerized in the presence of said liquid catalyst formulation at a temperature comprised between 140 and 220°C.

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