WO2013184014A1

WO2013184014A1 - Process for preparing high molecular weight poly(lactic acid) by melt polycondensation

Info

Publication number: WO2013184014A1
Application number: PCT/PT2013/000035
Authority: WO
Inventors: Cristina Maria DOS SANTOS GAUDÊNCIO BAPTISTA; Dina Augusta SIMÕES MARQUES; Maria Helena Mendes Gil
Original assignee: Universidade De Coimbra
Priority date: 2012-06-06
Filing date: 2013-06-06
Publication date: 2013-12-12

Abstract

The present invention is related to the process for preparing biodegradable materials, namely poly (lactic acid) having molecular weight from 50000 to 350000 g.mol^-1 and optical purity from 60 to 99%, with yields above 70% and reaction times below 30 h, by polymerization using melt polycondensation of lactic acid monomers using multifunctional agents, which comprises the following steps: a) a partial lactic acid distillation and simultaneous self-condensation carried out at atmospheric pressure or under vacuum, at increasing temperature up to 160-180°C, under inert atmosphere, with stirring; and b) a further melt polycondensation by adding a polycondensation catalyst, a thermal stabilizer and performing a simultaneous stepwise increase in vacuum to below 15 mbar and temperature up to 180-200°C, under inert atmosphere and stirring; wherein during the whole process an efficient removal of the byproduct water from the vapour phase is achieved by connecting to the polymerization vessel a reflux column containing a heat-transfer fluid, which allow the reflux of monomer, lactide ans small oligomers.

Description

DESCRIPTION

"PROCESS FOR PREPARING HIGH MOLECULAR WEIGHT POLY (LACTIC

ACID) BY MELT POLYCONDENSATION"

Field of the Invention The present invention is related to the process for preparing biodegradable materials, namely poly (lactic acid) ( PLA) , by melt condensation

Background of the Invention

PLA is a synthetic biodegradable polymer obtained from a 100 % renewable monomer, lactic acid, being one of the most promising substitutes for petrochemical origin materials. Due to its chemical, mechanical and physical properties, PLA has a large range of applications in the biomedical field (with the US Food and Drug Administration approval) and in conventional large scale polymer applications (fibres, films, composites, packaging, textile and general plastic materials) [Garlotta D. J Polym Environ 2002;9:63-84; Gupta AP, Kumar V. Eur Polym J 2007 ;43:4053- 4074 and Nampoothri KM, Nair NR, John RP, Bioresour Technol 2010;101:8493-8501] .

The ring opening polymerization process for producing high molecular weight PLA, already at industrial scale, requires several high energy consuming reaction stages, which increase production costs [Garlotta D. J Polym Environ 2002;9:63-84; Gupta AP, Kumar V. Eur Polym J 2007 ,-43:4053-4074 and Nampoothri KM, Nair NR, John RP. Bioresour Technol 2010;101:8493-8501], rendering prohibitive PLA's usage in large scale applications.

The continued depletion of landfill space, the diminution of petroleum resources and the problems associated with incineration of waste have led to the need for developing truly biodegradable polymers to be used as substitutes for non-biodegradable or partially biodegradable petrochemical-based polymers.

Although problematic in the past, recycling can offer an environmentally attractive disposal option for plastics. However, recycled plastics are typically contaminated with other incompatible materials and thus have reduced properties. Consequently, recycled plastics are often relegated to low-performance and low-value applications. In contrast, PLA articles can be readily hydrolyzed with water to form lactic acid, which is then purified and polymerized to remake the prime polymer. Additionally, PLA can also be biologically degraded in compost facilities offering more waste managing options.

PLA is synthesized from a 100 % renewable raw material, lactic acid, being one of the most promising thermoplastics. Due to its properties, PLA has a large range of applications. It is already widely used in biomedical applications such as: drug delivery systems, bone resorbable implants and tissue engineering, and it is approved by the US Food and Drug Administration (FDA) . More recently, PLA has been used in the conventional large scale polymer applications such as: fibres, films, composites and packaging. Additionally, this biodegradable polymer can be easily processed by the conventional processing techniques used for thermoplastics like injection moulding thermoforming and extrusion. Therefore, it has gained a growing economical relevance in recent years and an increasing, commercial interest is expected in the future [Garlotta D. J Polym Environ 2002;9:63-84; Gupta AP, Kumar V. Eur Polym J 200 ; 43 : 4053-4074 and Nampoothri KM:, Nair NR, John RP. Bioresour Technol 2010;101:8493-8501].

To be shaped into useful devices and to exhibit good mechanical properties, PLA must have a high molecular weight, at least 100 000 g.mol^""1. However, PLA with a molecular weight lower than 100 000 g.mol^"1 is also useful. PLA Can be prepared by both direct condensation of lactic acid and by the ring-opening polymerization (RGP) of the cyclic dimmer, the lactide. Because the direct condensation route is an equilibrium reaction, difficulties in removing trace amounts of water in the late stages of polymerization generally limit the ultimate molecular weight achievable by this approach. Based on physical properties, Dorough (U.S. Pat. No. 1995970) admitted and disclosed that the low molecular weight of the resulting poly (lactic acid) was due to a competing depolymerization reaction in which the cyclic dimer of lactic acid, the lactide, was generated, reducing the commercial value of the resulting poly (lactic acid) polymer. Since then, most research studies have been focused on the ROP of lactide.

The commercial large scale process for producing high molecular weight PLA involves the ROP of an intermediate compound, the lactide, in the presence of the stannous octoate catalyst (U.S. Pat. No. 5357035). The ROP is a step by step process which starts with the synthesis of small oligomers of lactic acid. These oligomers are further converted into a mixture of stereoisomers of the cyclic dimmer, the lactide. The lactide is further purified by distillation to remove water, lactic acid and oligomers and is finally polymerized by ring opening leading to high molecular weight PLA. This is an effective but quite complex process that requires highly energy consuming unit operations, increasing the production costs and the process environmental footprint.

Attempts to improve the processing characteristics of PLA synthesized by ROP have tended to focus on introducing long-chain branching through some mechanism. For example, it has been attempted to copolymerize the lactide with an epoxidized fat or oil, as described in U.S. Pat. No. 5359026, or with a bicyclic lactone comonomer, as described in WO 02/100921A1. It has been proposed to treat PLA with peroxide (U.S. Pat. Nos. 5594095 and 5798435), and to use certain polyfunctional initiators in its polymerization (U.S. Pat. Nos.. 5210108 and 5225521). U.S. Pat. No 7566753B2 describes the synthesis of branched PLA with improved melt rheological properties by copolymerization of a PLA polymer obtained by ROP with an epoxy acrylate copolymer.

Another particularly suitable process for preparing PLA by polymerizing the lactide is described in U.S. Pat. Nos. 5247059, 5258488 and 5274073. This preferred polymerization process typically includes a devolatilization step during which the free lactide content of the polymer is reduced, preferably to less than 1% by weight, and more preferably to less than 0.5% by weight, In order to produce a melt-stable lactide polymer, it is preferred to remove or deactivate the catalyst at the end of the polymerization process. This can be done by precipitating the catalyst or preferably by adding an effective amount of a deactivating agent to the polymer. Catalyst deactivation is suitably performed by adding a deactivating agent to the polymerization vessel, preferably prior to the devolatilization step. Suitable deactivating agents include carboxylic acids, of which polyacrylic acid is preferred; hindered alkyl, aryl and phenolic hydrazides; amides of aliphatic and aromatic mono- and dicarboxylic acids; cyclic amides, hydrazones and bis-hydrazones of aliphatic and aromatic aldehydes, hydrazides of aliphatic and aromatic mono- and dicarboxylic acids, bis-acylated hydrazine derivatives, phosphite compounds and heterocyclic compounds .

High molecular weight PLA can also be produced by polycondensation of lactic acid in solution using high boiling point solvents and molecular sieves as drying agents for an efficient water removal. It allows the synthesis of high molecular weight PLA, up to 100 000 g.mol^-1, from the monomer in one single reaction step (U.S. Pat. No 5310865) . However, this method presents drawbacks, namely the use of organic solvents which are harmful to the environment. Therefore a further purification stage to remove the solvent from the polymer is necessary. In a previous work [Marques DS, Jarmelo S, Baptista CMSG, Gil MH. Macromol Symp 2010;296:63-71] the authors reported the ynthesis of high molecular weight PLA, up to 80 000 g.mol^" ¹, in xylene. Although the molecular weight was high, the resort to organic solvents narrows the range of PLA applications and does not contribute to a sustainable environment, therefore supporting the search for alternative routes.

According to a literature survey, in order to overcome the previous disadvantages, some studies have been c rried out on the melt lactic acid polycondensation, i.e. in the absence of solvents. In 2001_/ Moon et al. published some results on the melt polycondensation of lactic acid, at high temperature, using vacuum to remove water, the byproduct, but high molecular weight was not reached [Moon S, Taniguchi I, Miyamoto M, Kimura Y, Lee C. High Perform Polym 2001; 13: S189-S196] . Similar findings were recently published by Sedlarik et al. (2010) where the highest molecular weight achieved by lactic acid melt polycondensation was 17 200 g.mol ^-1 [Sedlarik V, Kucharczyk P, Kasparkova V, Drbohlav J, Salakova A, Saka P. J Appl Polym Sci 2010;116:1597-1602], Chen et al., in 2006, were able to obtain PLA with 130 000 g. mol^-1 by direct lactic acid melt polycondensation by increasing the reaction time up to 40 h [Chen G-X, Kim H-S, Kim E-S, Yoon J-S. Eur Polym J 2006;42:468-472]. The required reaction time is excessive from an industrial point of view and its effect oil polydispersity index and the yellowing phenomena observed in bulk polymerizations were not properly assessed. To increase the molecular weight, Moon et al. (2001) submitted the polymer to a further solid state polymerization (SSP) that involves heating the sample to a temperature between glass and melting transition temperature [Moon S, Taniguchi I, Miyamoto M, Kimura Y, Lee C. High Perform Polym 2001;13:S189-S196] . The reaction takes place in the amorphous region of the polymer, where the reactive end groups and the catalyst are. However, the severe operating conditions favour side reactions that lead to yellowing, as a result of thermo-oxidative reactions.

Another process reported in the literature for increasing the molecular weight after lactic acid polycondensation is chain-extension. According to Bonsignore (U.S. Pat. 5470944), the expense to produce premium purity poly (lactic acid) products using current methods of condensation polymerization of free acids and catalytic ring opening polymerization is. quite large, due to the small weights of the polymers obtained and subsequently submitted to chain-extension. The scope of the invention presented in his document is to provide an improved poly (lactic acid) polymer and copolymer of high molecular weight by coupling lower molecular weight units using difunctional coupling agents such as: diisocyanates, bisepoxides, bisoxazolines and bis-ortho esters. These chain-linking agents react with a prepolymer, previously modified with hydroxyl or carboxyl end groups, increasing the length of the polymer chain. However, this approach requires a strict control of the reaction conditions because excess of chain-linking or long reaction times lead to crosslinking reactions. A similar process was reported in 1996 by Hiltunen et al. This process comprises a first step where the lactic acid is polymerized, in the presence of a diol, to a low-molecular-weight hydroxylterminatedprepolymer and then the molecular weight is increased by reacting the prepdlymer with a diisocyanate as the chain extender, obtaining a thermoplastic poly (ester-urethane) [Hiltunen K, Seppala J, Harkonen M. J Appl Polym Sci 1996;64:865-873].

The CN101007867 patent disclosures a three steps process to synthesise PLA. First step consists on monomer oligomerization by dehydration, followed by melt polycondensation and a further reactive extrusion. The reactive extrusion is performed in a twin-screw extruder in the presence of phosphorous acid esters compounds as chain extenders, resulting PLA polymers up to 40 000 g.mol^-1 viscosity-average molecular weight. The third reaction step adds complexity and cost to the process and the crosslinking reactions promoted by some phosphorous ester compounds narrow end polymer applications.

The U.S. Pat. No 5434241 discloses a relatively simple process for preparing at least 4-arm star shaped PLA with a molecular weight about 68 000 g.mol^-1 by melt lactic acid polycondensation, for 72 h, using polyhydroxyl compounds. This work showed that using a multifunctional compound enables attaching several PLA chains in a final higher molecular weight molecule. Although reaching higher molecular weight than the linear PLA obtained by direct lactic acid melt polycondensation, it remains too low for general purposes, and reaction time is excessive from an industrial point of view. A limited variety of multifunctional molecules were tested, only polyhydroxyl molecules with 4 or more functional groups, therefore failing synthesising PLA with a reduced branched structure. Mechanical performance of polymeric materials is highly dependent on molecular weight but also on molecular structure. In order to prepare PLA by lactic acid melt polycondensation with similar mechanical properties to the PLA currently prepared by ROP, highly branched structures are not advantageous. In spite of all research work devoted to the development of an alternative process to the ROP, this goal remains a challenge. Melt polycondensation results on PLA synthesis are promising: the process involves fewer stages and is more efficient from an energy point of view. Increasing polymer molecular weight and production rate are still aimed and a solid contribution to this is here described. Brief Description of the Drawing

Figure 1 shows the torque progress during the overall process from monomer distillation to the final polymerization stage. Torque measurements allow estimating melt viscosity which correlates very well with average molecular weight. The information in Figure 1 depicts a significant molecular weight increase when using a multifunctional agent (Empty dots - Example 6 on table 1) as compared to the its absence (Full dots - Example 0 on table 1) .

Summary of the Invention

The present invention provides a process for synthesising high molecular weight PLA by direct melt lactic acid polycondensation, in the presence of a multifunctional initiator, reducing reaction time while increasing final molecular weight, with the advantage of significant production cost reduction. Detailed description of the invention

This invention provides a low reaction time process for synthesizing high molecular weight poly (lactic acid) by lactic acid melt polycoridensation. Yield above 80% and reaction time up to 24 hours allow a significant reduction in production costs, while reaching molecular weights greater than 100 000 g.mol^-1 and optical purity higher than 75%. This is accomplished using multifunctional agents together with a strict control over reaction conditions. The stirring and the increasing temperature and vacuum profiles are crucial for achieving rapid byproduct diffusion from the progressively more viscous polymerization medium. The byproduct, water, is removed in a reflux column while the monomer, the lactide and small oligomers are effectively refluxed into the reaction vessel ensuring high poly (lactic acid) yields. Several multifunctional compound can be added enabling obtaining PLA with a wide range of molecular weights and different molecular structures, from linear to slightly or highly branched, and therefore with different properties. The process and each of its important parameters will be detailed below.

Object of the Invention

The. object of the invention is a process for preparing poly (lactic acid) having molecular weight from 50000 to 350000 g.mol^"1 and optical purity from 60 to 99%, with yields above 70% and reaction times below 30 h, by polymerization using melt polycondensation of lactic acid monomers using multifunctional agents, which comprises the following steps: a) a partial lactic acid distillation and simultaneous self-condensation carried out at atmospheric pressure or under vacuum, at increasing temperature up to 160-180°C, under inert atmosphere, with stirring; and

b) a further melt polycondensation by adding a polycondensation catalyst, a thermal stabilizer and performing a simultaneous stepwise increase in vacuum to below 15 mbar and temperature up to

180-200°C, under inert atmosphere and stirring; wherein during the whole process an efficient removal of the byproduct water from the vapour phase is achieved by connecting to the polymerization vessel a reflux column where the circulating heat transfer fluid allows the reflux of monomer, lactide ans small oligomers .

Usually, the temperature of the heat-trartsfer fluid in the reflux column should be higher than the water boiling point.

The above step a) is, normally, carried out at an increasing temperature up to 170 °C. Preferably, in the above step b) the polycondensation catalyst is selected from the group consisting of tin powder, stannous chloride, stannous oxide, stannous oetoate, dibutiltindilaurate, antimony oxide, titanium oxide, zinc oxide., zinc acetate, manganese acetate, titanium manganese, p-toluenesulphonic acid, sulphuric acid and phosphoric acid, the thermal stabilizer is a phosphorous compound and the efficient removal of the byproduct water is performed for less than 20 h.

The amount of catalyst is, generally, between 0.2 and 0.6 wt % .

The preferred catalyst is tin powder.

The tin powder is, advantageously, recovered in a granular form from the bottom of the reactor.

The preferred phosphorous compound is triphenylphosphine .

In a preferred embodiment the water is removed from the increasingly viscous polymer bulk by stirring speed of 400-800 rpm, by increasing temperature stepwise to 180 or 190°C, by increasing the vacuum stepwise to below 10 mbar, under inert atmosphere.

The preferred molecular weight of the of poly (lactic acid) is from 70 000 to 300 000 g.mol^"1. The optical purity of poly (lactic acid) is, preferably, from 75 % to 98 %. The polymerization process is undertaken, with advantage, in an inert atmosphere, while bubbling nitrogen with purity at least 99,99 %, into the reaction medium.

Normally, the multifunctional agents have at least two functional groups and are selected from different polyalcohols, polyacids, polyamines, anhydrides, polyepoxides, isocyanates, silanes or a combination of different functional groups. Ina a preferred embodiment linear poly (lactic acid) or branched poly (lactic acid) with at least three branches is obtained.

Experimental Part

The process uses as initial monomer a lactic acid solution. To get a viscous oligomer mixture the first stage of the process consists in the distillation and simultaneous self-condensation of the monomer under atmospheric pressure or under vacuum, at an increasing temperature up to 170-180°C, using mechanical stirring, while an inert gas is bubbled into the reaction medium. Once water has been removed, a suitable catalyst, or a combination of catalysts, is added to the process, usually a metal based compound. Then, an increase in temperature in the range of 10-20°C is carried out, while other operating conditions remain the same, and the reaction system is kept under these conditions for approximately 1 hour. After that, the process proceeds with a gradual pressure reduction from atmospheric to below 10 mbar during less than 10 hours and is longer kept under these operating conditions. At the end of the polymerization, up to 24 hours, the melt polymer is poured into a plate and allowed to cool. A few grams of this polymer are dissolved in chloroform, transferred to a Petri dish and the chloroform evaporation is allowed in order to form a colourless or slightly coloured, transparent and flexible PLA film. The selected multifunctional agent can be added at the beginning of the polymerization or at a further stage. The average molecular weights of the polymer samples range from 50 000 to 350 000 g.mol^"1.

The multifunctional agents include any compound, with at least two functional groups, capable of a condensation reaction of the low molecular weight PLA prepolymer, either with the hydroxyl or carboxyl group of the lactic acid monomer, in order to link low molecular weight PLA chains into a higher molecular weight PLA molecule. This strategy allows the synthesis of linear structures, similar to the PLA synthesized by ROP, and branched ones, with at least three arms. The resource to a multifunctional agent allows the synthesis of a wide range of molecular structures with different properties and, therefore, its selection is a critical issue. The multifunctional agent is selected from different polyalcohols, polyacids, polyamines, anhydrides, polyepoxides, isocyanates, silanes or a combination of different functional groups. Examples of multifunctional compounds to be used are: pentaerythritol, dipentaerythritol , tripentaerythritol, sorbitol, castor oil glycidyl ether, bisphenol A diglycidyl ether, pyromellicdianhydride, ethylenediaminetetraacetic acid, diethylenetriaminepentaacetic acid, diethylenetriaminepentaacetic acid anhydride, poly(maleic anhydride-acrylic acid copolymer) , citric acid, triethanolamine, tetrakis (2-hydroxyethyl) ethylenediamine, tris (2-aminoethyl) amine, hexamethylenediisocyanate, isophoronediisocyanate and tetraethyl orthosilicate.

The catalyst used to accelerate the polymerization reaction may be a conventional polycondensation catalyst such as: stannous chloride, stannous oxide, stannous octoate, dibutiltindilaurate, tin powder, antimony oxide, titanium oxide, zinc oxide, zinc acetate, manganese acetate, titanium manganese, p- toluenesulphonic acid, sulphuric acid, phosphoric acid, triphenylphosphine or an appropriate combination. The amount of catalyst used in this process is 0.2 to 0.6 wt %, based on the monomer amount, preferably 0.4 wt %, in order to reach a good balance between high molecular weight and low side reactions' s extent. The preferred catalyst is tin powder since it allows the synthesis of high molecular weight PLA and offers the possibility to be recovered in a granular form from the melt polymer and recycled, avoiding the disadvantageous procedures of precipitation or deactivation and providing a safe and stable PLA for processing and for biomedical applications. Polarity changes in reaction medium affect catalytic activity. Therefore, catalysts are added after initial monomer distillation. Depending on the catalyst employed, reaction conditions such as high temperature and long reaction time may lead to yellowing, due to thermo-oxidation, and low optical purity, caused by racemiza ion reactions [Hiltunen K, Seppala J, Harkonen M. Macromolecules 1997; 30: 373] . The resulting reduction in optical purity has an adverse effect upon thermal and mechanical properties of the polymer and discoloration becomes a critical issue when applications require optically clear materials. The common strategy used at large-scale production of commercial polyesters such as poly (ethylene terephalate) (PET) consists in using phosphorous compounds as thermal stabilizer, together with the polymerization catalyst, to prevent discoloration reactions during the polycondensation process and subsequent processing [U.S. Pat. No 5922828 and Pang K, Kotek R, Tonelli A. Prog Polym Sci 2006; 31 : 1009] . The use of these compounds, preferably triphenylphosphine, added with the lactic acid polycondensation catalyst in an equimolar ratio, was confirmed as very effective, hindering side reactions during PLA synthesis and allowing obtaining PLA with better colour properties, higher optical purity and without significantly affecting the molecular weight. The lactic acid monomer used in this process is a hydroxy acid, with two optical isomers (L and D form) . Any of these isomers or a mixture of both can be used in the process. However, the L isomer is often preferred since it is the isomer predominantly obtained in the fermentative process [Garlotta D. J Polym Environ 2002;9:63-84]. The starting lactic acid may be used in the form of an aqueous solution at various concentrations. The lactic acid polycondensation is a reversible reaction, and in order to increase the molecular weight the byproduct, water, must be continuously withdrawn. Unfortunately, an increase in polymer molecular weight is inevitably associated to an increase in melt viscosity which jeopardizes water removal. Moreover, such high viscosity is difficult to handle and introduces particular requirements when selecting equipment. To improve water removal, the polycondensation reaction is carried out under vacuum, high temperature, stirring and inert atmosphere, in an appropriate batch polycondensation system that will be conveniently described below. The gas used may be nitrogen with a very low oxygen and moisture content, typically with residual traces of oxygen from 2 to 5 ppm. In order to ensure that the water is efficiently removed from, the vapour phase vacuum is applied. As the viscosity increases during the reaction, the level of vacuum is increased stepwise to below 10 mbar, depending on the vacuum pump capability. While water is being eliminated, the operating conditions allow small molecules such as monomer, lactide and small oligomers to be also taken from the reaction mixture, jeopardizing the polymer yield and the molecular weight achieved. A fractionating section, connected to a vacuum pump, is required at the top of the reactor 'throughout the process to selectively distil off the water and reflux these compounds. Therefore, the chemical reaction equilibrium is selectively shifted toward the polymer formation. Reintroduction of these compounds is essential to ensure high molecular weight PLA and high yield. However, some compounds crystallise and remain trapped in the equipment walls. Therefore, the temperature in the reflux column should be higher than the lactide melting point, to avoid its crystallization, and higher than the water boiling point, to ensure that only water is selectively distilled off and recovered in a cold trap.

The stirring is used throughout the process to improve water removal and reaction extent. The combination of a rapid surface renewal obtained by stirring and the bubbling of an inert gas into the reaction mixture enhances the mass transfer of the byproduct water from the melt polymer to the vapour phase, which is then removed by vacuum. As polymerization proceeds and the melt viscosity increases, mass transfer becomes highly dependent on the surface renewal rate and surface area available. Therefore, polymerization reactors that offer high surface area should be preferred. The stirrer should be suitable for highly viscous materials, preferred anchor stirrer, and should be set at an adequate stirring rate ensuring rapid water diffusion. In order to avoid air leaks, . a magnetic coupling should be used to connect the stirrer to the stirrer head. At large scale production, the viscosity plays an important role being often selected for inline monitoring of the polyesters production by measuring torque. This is a very good method for melt viscosity estimation and this correlates very well with average molecular weight, thus, stirrer head should provide torque measuring.

A strict control of the reaction conditions, mainly temperature, should be achieved. Low temperature does not favour the polymerization reaction. High temperature may enhance water removal, but depolymerization and thermo-oxidative reactions are favoured. Consequently high molecular weight PLA with required properties is difficult to synthesise. Temperatures in the range 170 to 200 °C may be employed and a stepwise increase in temperature during the process is advantageous.

The average molecular weight (Mw) is determined by Size Exclusion Chromatography (SEC) , the equipment is calibrated with narrow polystyrene standards (4 000, 10 050, 19 880, 30 300, 66 350, 96 000 and 200 000 g.mol^"1) . The column set consists of a Polymer Laboratory 5μπι guard column (50x7.5mm) followed by one PLgel 5pm MIXED-D column (300x7.5 mm). The HPLC pump is set with a flow rate of 0.6 mL.min^"1 and the eluent is HPLC grade Chloroform. The measurements are carried out at 25 °C with a concentration of approximately 2 mg.mlT¹ of polymer sample, after purification by precipitation. Before the injection (~. 50 μ ) , the samples are filtered through a PTFE membrane with a 0.45 μπ pore. After column exclusion, the samples are analysed in an evaporative light scattering detector, PL- E D 960. Data processing is carried out with GPC Clarity software from DataApex.

The specific rotation of PLA polymers, [ώ] , is measured in an Optical Activity AA-5 electrical polarimeter at 25°C, with a wavelength of 589 nm and a concentration of 1 g.dL^-1 in chloroform. The percentage of optical purity of PLA polymers (OP) is calculated using the following relationship [Marques DS, Jarmelo S, Baptista CMSG, Gil MH. Macromol Symp 2010;296:63-71]:

Γ 125

0/^>(%) = ISJ-^!ixioO (1)

—156 where -156 is the specific rotation of PLA with only L stereoisomer in its composition.

Yield is another important criterion to assess a process. Considering that during polymerization each mole of monomer releases one mole of water, the yield was calculated using the following equation:

Yield(%) = ^Weight °^{f pr0duCt} xlOO (2)

Weight of monomer x0.8 Examples

Examples 1, 2, 3, 4, 5, 6 and 7

The batch polycondensation reactor described above is charged with 200 mL of 80 wt % L-lactic acid solution and the multifunctional agent according to table 1. The water is allowed to distil off at up to 170 °C, under inert atmosphere and mechanical stirring (600 rpm) . After no more water is being removed, 0.78 g of tin powder are added, the temperature is raised to 190 °C and the reaction system is kept under these conditions for approximately 1 hour. Then, the pressure is reduced gradually from atmospheric to below 10 mbar during around 7 hours, and kept under these conditions during 4 hours. At the end of the polymerization, around 130 g of melt polymer are poured into a plate and allowed to cool. Few grams of polymer are dissolved in chloroform, poured into a Petri dish and chloroform evaporation is allowed to form a colourless, or slightly coloured, transparent and flexible PLA film.

The preferred catalyst is tin powder since it offers the possibility to be recovered in a granular form from the melt polymer and recycled, thus providing a safe and stable PLA for processing and for intended applications . Torque measurement is a very good method for melt viscosity estimation and correlating with average molecular weight [Scheirs J, Long TE. Wiley&Sons 2003] . Thus, torque measurement has been recorded for polymerization control. Figure 1 shows the torque profile during lactic acid polycondensation in bulk with multifunctional agent (branched PLA) , Example 6 in Tablel, and without multifunctional agent (linear PLA), Example 0 in Tablel. It is striking that the addition of a small quantity of multifunctional agent has a dramatic influence upon polymer melt viscosity and therefore on polymer molecular weight.

Examples 8 and 9 The batch polycondensation reactor is charged with 200 mL of 80 wt % L-lactic acid. The water is allowed to distil off at up to 170 °C, under . inert atmosphere and mechanical stirring (600 rpm) . After no more water is being removed 0.78 g of tin powder are added, the temperature is raised to 190 °G and the reaction system is kept under these conditions for approximately 1 hour. Then, the pressure is gradually reduced from atmospheric to below 10 rtibar during about 7 hours and kept under these conditions during around 2 hours. Finally, nitrogen is introduced until reaching atmospheric pressure. The multifunctional agent is added, according to table 1, and allowed to react for circa 2 hours. At the end of the polymerization, around 130 g of melt polymer are poured into a plate and allowed to cool. A few grams of polymer are dissolved in chloroform, transferred to a Petri dish and chloroform evaporation is allowed to form a colourless, or slightly coloured, transparent and flexible PLA film. Exemplo 10

The batch polycondensation reactor is charged with 200 mL of 80 wt % L-lactic acid and 0.54 ml of 1,4- butanediol . The water is allowed to distil off at up to 170 °C, under inert atmosphere and mechanical stirring (600 rpm) . After no more water is being removed 0.78 g of tin powder are added, the temperature is raised to 190 °C and the reaction system is kept under these conditions for 1 hour. Then, the pressure is gradually reduced from atmospheric to below 10 mbar during 7 hours and kept under these conditions during 2 hours. Finally, nitrogen is introduced until reaching atmospheric pressure, the multifunctional agent is added, according to table 1, and allowed to react for 2 hours. At the end of the polymerization, around 130 g of melt polymer are poured into a plate and allowed to cool. Few grams of polymer are dissolved in chloroform, poured into a Petri dish and chloroform evaporation is allowed to form a colourless, transparent and flexible PLA film.

Results

The results obtained using different multifunctional agents, are shown in Table 1. Table 1

Exaaple MoltifunctLcrial Mi~ltifunctional Mt Optical Torque Yield Time

Agent Agent Quantity (g.nor¹) Purity (Ncm) (%) (h)

(g) (%)

0 None None 50000 81 20 77 24

1 Pentaerithritol 0.21 113000 88 76 87 24

2 Dipentaerythritol 0,57 114 000 91 76 81 24

3 Tripentaerythritol 0.63 120500 86 79 83 24

4 Ethylenediamine- 0.61 66500 87 34 86 24 tetraacetic acid

5 Castor oil 1.13 89000 93 60 85 24 glycidyl ether

6 Bisphenpl A 0.52 114 500 88 94 82 24 diglycidyl ether

7 Triethanolamine 0.31 58500 89 70 81 24

8 Hexamethylene 10.4 200000 78 41 90 24 diisocyahate

9 Bisphenpl A 0.52 53000 86 9.7 87 24 diglycidyl ether

10 Hexamethylene 10.4 310000 80 46 91 24 diisocyanate Industrial application

PLA is a biodegradable, thermoplastic, aliphatic polyester synthesized from lactic acid, which is produced from renewable resources such as corn, potatoes, wheat, tapioca, corn starch or sugar carie.

In the 21^st century, increased utilization of renewable resources is considered to be one of the strong drivers for sustainable products. Reduced energy consumption, waste minimization, and reduction of greenhouse gases emission are major concerns and taking on greater emphasis. PLA is the first commodity plastic to integrate these principles and its application as a cost- effective alternative to commodity petrochemical-based plastics will increase demand for agricultural products, such as corn and sugar beet, raw materials for lactic acid production. Overall PLA is a clear example of sustainable technology.

Art additional driver to large commercial production of PLA from lactic acid is the increasing availability and reduced cost of lactic acid. PURAC™ has been the world's largest producer of lactic acid and NatureWorks™ (with a capacity of 4.00 000 000 lb) is the major producer of PLA, being awarded with the 2002 Presidential Green Chemistry Award for their process to produce Ingeo® PLA.

Future developments will include blends of PLA, copolymers, and impact-modified products, which will further expand the applications of this unique polymer [Henton D, Gruber P, Lunt J, Randall J. Natural Fibers, Biopolymers, and Biocomposites 2005] .

However, the commercial ROP process for producing high molecular weight PLA, used by Natureworks™, requires several high energy consuming reaction and purification stages, which increase production costs.■ The work described herein provides a process for synthesizing high molecular weight PLA by direct melt lactic acid polycondensation, in the presence of a multifunctional compound, which offers the advantage of significant reduction in production costs. This technical advantage might be of great interest for PLA producers, as this polymer takes on significant value in both short-term and durable applications..

Claims

1. A process for preparing poly (lactic acid) having molecular weight from 50000 to 350000 g.rnol^"1 and optical purity from 60 to 99%, with yields above 70% and reaction times below 30 h, by polymerization using melt polycondensation of lactic acid monomers using multifunctional agents, which comprises the following steps: a partial lactic acid distillation and simultaneous self-condensation carried out at atmospheric pressure or under vacuum, at increasing temperature up to 160-180°C, under inert atmosphere, with stirring; and

a further melt polycondensation by adding a polycondensation catalyst, a thermal stabilizer and performing a simultaneous stepwise increase in vacuum to below 15 mbar and temperature up to 180-200°C, under inert atmosphere and stirring; wherein during the whole process an efficient removal of the byproduct water from the vapour phase is achieved by connecting to the polymerization vessel a reflux column containing a heat-transfer fluid, which allow the reflux of monomer, lactide ans small oligomers.

2. The process according to claim 1, wherein the temperature of the heat-transfer fluid in the reflux column should be higher than the water boiling point.

3. The process according to claim 1 or 2, wherein step a) is carried out at an increasing temperature up to 170 °C.

4. The process according to anyone of the claims 1 to 3, wherein in step b) the po.lycondensation catalyst is selected from the group consisting of tin powder, stannous chloride, stannous oxide, stannous octoate, dibutiltindilaurate, antimony oxide, titanium oxide, zinc oxide, zinc acetate, manganese acetate, titanium manganese, p-toluenesulphonic acid, sulphuric acid and phosphoric acid, the thermal stabilizer is a phosphorous compound and the efficient removal of the byproduct water is performed for less than 20 h.

5. The process according to claim 4, wherein the amount of catalyst is between 0.2 and 0.6 wt %.

6. The process according to claim 4 or 5, wherein the catalyst is tin powder.

7. The process according to claim 6, wherein the tin powder is recovered in a granular form from the bottom of the reactor.

8. The process according to claim 4, wherein the phosphorous compound is triphenylphosphine.

9. The process according to claim 4, wherein the water is removed from the increasingly viscous polymer bulk by stirring speed of 400-800 rpm, by increasing temperature stepwise to 180 or 190°C, by increasing the vacuum stepwise to below 10 mbar, under inert atmosphere.

10. The process according to any one of claims 1 to 9, wherein the molecular weight of the of poly (lactic acid) is from 70 000 to 300 000 g.mol^""1.

11. The process according to any one of claims 1 to 10, wherein the optical purity of poly (lactic acid) is from 75 % to 98 %.

12. The process to any one of claims 1 to 11, wherein the polymerization process is undertaken in an inert atmosphere, while bubbling nitrogen with .purity at least 99, 99 %, into the reaction medium..

13. The process according to any one of claims 1 to 12, wherein the multifunctional agents have at least two functional groups and are selected from different polyalcohols, polyacids, polyamines, anhydrides, polyepoxides, isocyanates, silanes or a combination of different functional groups.

14. The process according to any. one of claims 1 to 13, wherein linear poly (lactic acid) or branched poly ( lactic acid) with at least three branches is obtained.