WO2013108271A1 - A solvent free process for preparation of high molecular weight polylactide catalyzed by a compound of a divalent metal and an acid resulting in corresponding stereo selective polylactide - Google Patents

A solvent free process for preparation of high molecular weight polylactide catalyzed by a compound of a divalent metal and an acid resulting in corresponding stereo selective polylactide Download PDF

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WO2013108271A1
WO2013108271A1 PCT/IN2013/000033 IN2013000033W WO2013108271A1 WO 2013108271 A1 WO2013108271 A1 WO 2013108271A1 IN 2013000033 W IN2013000033 W IN 2013000033W WO 2013108271 A1 WO2013108271 A1 WO 2013108271A1
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polylactide
solvent free
free process
zinc
molecular weight
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PCT/IN2013/000033
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French (fr)
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Baijayantimala Garnaik
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Council Of Scientific & Industrial Research
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    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
    • C08G63/78—Preparation processes
    • C08G63/82—Preparation processes characterised by the catalyst used
    • C08G63/823—Preparation processes characterised by the catalyst used for the preparation of polylactones or polylactides

Definitions

  • the present invention relates to a one pot solvent free process for preparation of high molecular weight polylactide catalysed by a precursor of a divalent metal and an acid resulting in corresponding stereo selective polylactide. Further, it also relates to ring opening polymerization of lactones (lactides)
  • Poly (lactic acid) or polylactide (PLA) is thermoplastic aliphatic polyester consisting of Lactic acid as its monomer unit. Due to the chiral nature of lactic acid, several distinct forms of polylactide exist. But Lactic acid cannot be directly polymerized to a useful polylactide. This is because; each polymerization reaction generates one molecule of water, the presence of which degrades the forming polymer chain to the point that only very low molecular weights are observed.
  • Another prior art discloses a process of obtaining high molecular weight PLA from the dilactate ester by ring-opening polymerization using a stannous octoate catalyst. This mechanism does not generate additional water, and hence, a wide range of molecular weights is accessible. But, tin can contaminate the end product and is therefore unacceptable. Also, tin links with PLA and cannot be isolated, as it leads to decrease in molecular weight. Further, tin being toxic, is not biocompatible and hence not accepted by the body.
  • the main objective of the present invention is to provide a solvent free process for preparation of high molecular weight polylactide catalysed by a compound of a divalent metal and an acid resulting in corresponding stereo selective polylactide.
  • Another objective is to provide the ring opening polymerization of lactide.
  • One more objective is to provide a process for preparation of high molecular weight polylactide without racemisation.
  • Yet another objective is to provide for the use of Zn prolinate as a catalyst in the said reaction to result in a biocompatible polylactide.
  • the present invention provides one pot solvent free process for preparation of high molecular weight poly L lactide comprising ring-opening polymerization of Lactides catalysed by a recrystallized form of a precursor of a divalent metal and an acidto result in poly L lactide of Mw>50,0O0. .
  • the divalent metal of the catalyst is selected from a group consisting of Be, Mg, Ca, Sr, Ba, Ra and transitional and inner transitional metals V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Mo, Rh, Pd, Ag, Cd, W, Re, Os, Ir, Pt, Hg, Sm, Eu, Tm, Yb.
  • the acid is selected from the group consisting of amino acids and hydroxyl carboxylic acids.
  • amino acids are selected from the group consisting of aliphatic, alicyclic or aromatic.
  • the catalyst is recrystallized Zinc prolinate.
  • the process is carried out at a temperature in the range of 180-200 5 C in an inert atmosphere.
  • the molar ratio of polylactide to Zinc prolinate is in the range of 200: 1 to 400:1.
  • the catalyst is recovered by dissolving PLA (polylactide ) in DCM ( dichloro methane) and precipitating the catalyst using deionized water.
  • Scheme 1 describes Synthesis of zinc prolinate catalysts
  • Figure 1 depicts X-ray structure of zinc-proline complex
  • Figure 2 depicts the characterization of recrystallized Zinc prolinate catalyst by solid state Cp/mass 13C NM (Cross polarization/magic angle spinning) at 500MHz.
  • Peak at 172 shows trace amounts of Zinc acetate
  • peak at 176.34 corresponds to carboxylic acid group present in L-proline not coordinated with Zinc
  • peak at 178.60 corresponds to carboxylic acid coordinated with Zinc.
  • Figure 3 depicts 1- 13 C quantitative NMR spectra (500 MHz) of sample PLA-4. The absence of a split carbonyl peak at 169.0 clearly shows that polymer is single isomer and proves that absence of racemisation of polymer by the process disclosed.
  • Figure 4 depicts Size Exclusion Chomatography elugram of PLA-4.SEC graph of PLA-7, from which the Mw has been calculated to be 100500.
  • FIG. 5 depicts differential scanning calorimetry (DSC) thermogram of PLA-4.
  • the DSC curve was obtained using Perkin Elmer instrumentation. The sample was heated from -40 5 C to 200 9 C at the rate of 10 9 C/minute under nitrogen atmosphere. Then it was held for 1 minute and cooled suddenly at the rate of lOO ⁇ C/minute. The sample is again heated from -40 9 C to 200 9 C at the rate of 10 9 C/minute. Tm and Tg values were calculated from first and third heating curves respectively.
  • the DSC clearly shows the presence of a single isomer,! isomer of polylactide.
  • the present invention provides a one pot process for the synthesis of high molecular weight polylactide using a non toxic catalyst which is readily recoverable.
  • the inventive process provides stereo selective polylactide without racemization.
  • High molecular weight polylactic acid was prepared from lactide by ring opening polymerization.
  • the divalent metal of the catalyst is selected from a group comprising (Group II) elements such as Be, Mg, Ca, Sr, Ba, Ra and transitional and inner transitional metals such as V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Mo, Rh, Pd, Ag, Cd, W, Re, Os, Ir, Pt, Hg, Sm, Eu, Tm, Yb and the acid is selected from the group comprising amino acids and hydroxyl carboxylic acids.
  • the amino acids are aliphatic, alicyclic or aromatic.
  • the most preferred catalyst of the invention is Zinc prolinate.
  • the catalyst employed is synthesized by stirring Zinc acetate (1 equiv.), L-proline (2 equiv.) and triethylamine (2 equiv.) in methanol. The complex is precipitated out from the methanolic solution and isolated.
  • the one pot process of the invention for the preparation of high molecular weight polylactide by ring-opening polymerization of Lactides (L,L- D,D- D,L- and meso) is carried out at a constant temperature in an inert atmosphere.
  • the requisite amount of lactide and freshly recrystallized catalyst are taken in silanized glass reactor.
  • the desired reaction temperature is set, the quartz reactor containing the reaction mixture is kept in the reactor chamber. After the completion of the reaction, the product is cooled under inert atmosphere.
  • the product was used for further characterization.
  • the catalyst can be recovered by dissolving PLA in DCM and precipitating using deionised water.
  • PLA-4 200:1 170 10 76,000 1,30,000 1.71
  • the process may be carried out at a temperature range of 150-200, preferably 170-200 deg C.
  • the catalyst zinc L-prolinate was synthesized by stirring zinc acetate Zri (OAc) 2 (1 equiv.), L- proline (2 equiv.) and triethylamine (2 equiv.) in methanol. The complex was precipitated out from the methanolic solution and isolated. Zinc D-prolinate was prepared by using similar procedure. The crude product was recrystallized thrice from 30 ml of a water/2- propanol mixture (1:1). After drying at 60°C over P 4 Oi 0 (phosphorus pentoxide) in vacuum, the yield was obtained as 99%.
  • Zinc salt of L-proline was compared with that of D-proline and found that zinc salt possessed similar structure.
  • Zinc salts e.g. that of L-proline and D-proline
  • Ci 0 Hi 6 N 2 O 4 Zn (291.60) calculated, C 40.91, H 5.48, N 9.54 and found C 40.90 H 5.53 N 9.4.
  • This catalyst is low hygroscopic.
  • Recrystallization of zinc prolinate was carried out using various proportions of isopropyl alcohol and water (90:10, 80:20, 70:30, 60:40, 50:50). The best result was obtained at 50:50 compositions.
  • the solid state 13C nmr confirmed the structure zinc prolinate.
  • the acid group of L- or D- proline makes complex with zinc metal. Some of the acid groups of L- proline are free even using zinc acetate and L- proline in 2:1 equivalent proportion. The equivalent of zinc acetate will be varied to achieve 100% complexation without any free acid groups of L- proline.
  • the spectroscopic data show the mononuclear zinc (prolinate) 2 derivatives to be the prevailing species.
  • the complex was resulted from the reaction of zinc acetate with either (L or D) proline.
  • the two L-proline molecules are coordinated to the zinc atom via their N and carboxylic O atom.
  • the two bidentate ligands are Trans with respect to each other.
  • the zinc atom is pentacoordinate, fifth coordination site being occupied by the symmetry related O (4') (symmetry code: (i) 2-x, y-1/2, -z) of a neighbouring proline molecules, so that an infinite polymeric chain is generated.
  • the polymer shows a helical structure along the 2 1 direction.
  • the zinc coordination here is unique as most zinc amino acid complexes are hexadentate.
  • FTIR also confirmed the structure before and after the complexation with proline.
  • Zinc prolinate was characterized by thermo gravimetric analysis (TGA) and found stable up to 371°C.
  • Figure 2 depicts the characterization of recrystallized Zinc prolinate catalyst by solid state Cp/mass 13C NMR (Cross polarization/magic angle spinning) at 500MHz.
  • Peak at 172 shows trace amounts of Zinc acetate
  • peak at 176.34 corresponds to carboxylic acid group present in L-proline not coordinated with Zinc
  • peak at 178.60 corresponds to carboxylic acid coordinated with Zinc.
  • High molecular weight polylactic acid was prepared from lactide by ring opening polymerization technique.
  • the experimental procedure is given below:
  • Ring-opening polymerization of Lactides (L,L- D,D- D,L- and meso) was carried out at a 150-
  • This catalyst can also be recovered by dissolving PLA in DCM and precipitating using deionized water because that is in water soluble.
  • PLA 7 was characterized by 13C NMR.
  • Figure 3 depicts 1- 13 C quantitative NMR spectra (500 MHz) of sample PLA-4. The absence of a split carbonyl peak at 169.0 clearly shows that polymer is single isomer and proves that absence of racemisation of polymer by the process disclosed.
  • Figure 4 depicts Size Exclusion Chomatography elugram of PLA-4., from which the Mw has been calculated to be 1,30,000.
  • FIG. 5 depicts differential scanning calorimetry (DSC) thermogram of PLA-6, 6a and 7.
  • DSC differential scanning calorimetry

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  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
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Abstract

The use of a precursor of a divalent metal and an acid to catalyze formation of polylactides is known, but the challenge lies in synthesizing pure isomers and of high molecular weight by a solvent free process using compatible catalyst systems. This challenge is addressed by the inventors by disclosing a process of synthesizing poly L lactide of molecular weight > 50,000.

Description

A SOLVENT FREE PROCESS FOR PREPARATION OF HIGH MOLECULAR WEIGHT POLYLACTIDE CATALYZED BY A COMPOUND OF A DIVALENT METAL AND AN ACID RESULTING IN CORRESPONDING STEREO SELECTIVE POLYLACTIDE
FIELD OF THE INVENTION
The present invention relates to a one pot solvent free process for preparation of high molecular weight polylactide catalysed by a precursor of a divalent metal and an acid resulting in corresponding stereo selective polylactide. Further, it also relates to ring opening polymerization of lactones (lactides)
BACKGROUND AND PRIOR ART OF THE INVENTION
Poly (lactic acid) or polylactide (PLA) is thermoplastic aliphatic polyester consisting of Lactic acid as its monomer unit. Due to the chiral nature of lactic acid, several distinct forms of polylactide exist. But Lactic acid cannot be directly polymerized to a useful polylactide. This is because; each polymerization reaction generates one molecule of water, the presence of which degrades the forming polymer chain to the point that only very low molecular weights are observed.
Available prior art discloses a process wherein, two lactic acid molecules undergo a single esterfication process and are then catalytically cyclized to make a cyclic di-lactate ester. Although dimerization also generates water, it can be separated prior to polymerization due to a significant drop in polarity. But a major disadvantage of this process is that high molecular weight polylactides cannot be obtained using the same. Reference may be made here to Article titled "Homo and copolymerization of L,L- lactide in presence of zinc prolinate using ring opening polymerization" published in NCL Annual Report 2007-08 of Polymer Materials (Polymers from renewable resources) by Dr. (Mrs.) Baijayantimala Garnaik
Another prior art discloses a process of obtaining high molecular weight PLA from the dilactate ester by ring-opening polymerization using a stannous octoate catalyst. This mechanism does not generate additional water, and hence, a wide range of molecular weights is accessible. But, tin can contaminate the end product and is therefore unacceptable. Also, tin links with PLA and cannot be isolated, as it leads to decrease in molecular weight. Further, tin being toxic, is not biocompatible and hence not accepted by the body.
To overcome the disadvantages of tin, an attempt to prepare polylactide using Zinc prolinate by solution polymerization, was made, but did not succeed as racemization occurred. An article titled "Homopolymerization L-Lactide And D,L-Lactide in presence of Novel Zinc Prolinate Derivatives" published in Trade Science Inc. Vol. 6, Issue 4, 2010 by Asutosh Kumar Pandey discloses the ring opening polymerization of lactide and ε- caprolactorte in presence of zinc prolinate derivatives which gives polymers with wider spectrum of properties than the polymers synthesized by copolymerization of the corresponding hydroxyacids. Such ring opened copolymers is a mixture of L and D isomers of polylactide yield tough polymers with properties from rigid thermoplastics to elastomeric rubbers.
Hans R. Kricheldop, Dirk-Olaf Damrau in an article titled "Polymerization of L-lactide catalyzed by zinc amino acid salts" in Macromol. Chem. Phys. 199,1747-1752 (1998) discloses a process at 1505C conducted over 48-192 hours using Zinc prolinte catalyst resulting in polymer with viscosity in the range of 0.16-0.44 indicating the low molecular weight of polymer obtained. The authors further discuss that when temperatures is raised, mixtures of isomers are obtained.
Thus there is a need to employ a solvent free process for preparation of high molecular weight polylactides, without any racemisation reaction; preferably employing resorbable catalysts.
Also there is a need in the art to catalyse the reaction using non toxic catalysts.
An approach to solve the aforementioned problems has been provided by the present invention as the said invention relates to-
- A solvent free process for preparation of high molecular weight polylactide
Use of a compound of a divalent metal and an acid such as Zinc prolinate as the catalyst in the said reaction
- High molecular weight polylactide produced without racemisation in case of L,L- lactide,
OBJECTIVE OF THE INVENTION
The main objective of the present invention is to provide a solvent free process for preparation of high molecular weight polylactide catalysed by a compound of a divalent metal and an acid resulting in corresponding stereo selective polylactide.
Another objective is to provide the ring opening polymerization of lactide. One more objective is to provide a process for preparation of high molecular weight polylactide without racemisation.
Yet another objective is to provide for the use of Zn prolinate as a catalyst in the said reaction to result in a biocompatible polylactide.
SUMMARY OF THE INVENTION
Accordingly/ the present invention provides one pot solvent free process for preparation of high molecular weight poly L lactide comprising ring-opening polymerization of Lactides catalysed by a recrystallized form of a precursor of a divalent metal and an acidto result in poly L lactide of Mw>50,0O0. .
In one embodiment of the present invention the divalent metal of the catalyst is selected from a group consisting of Be, Mg, Ca, Sr, Ba, Ra and transitional and inner transitional metals V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Mo, Rh, Pd, Ag, Cd, W, Re, Os, Ir, Pt, Hg, Sm, Eu, Tm, Yb. In another embodiment of the present invention the acid is selected from the group consisting of amino acids and hydroxyl carboxylic acids.
In still another embodiment of the present invention the amino acids are selected from the group consisting of aliphatic, alicyclic or aromatic.
In yet another embodiment of the present invention the catalyst is recrystallized Zinc prolinate.
In yet another embodiment of the present invention the process is carried out at a temperature in the range of 180-2005C in an inert atmosphere. In yet another embodiment of the present invention the molar ratio of polylactide to Zinc prolinate is in the range of 200: 1 to 400:1.
In yet another embodiment of the present invention the catalyst is recovered by dissolving PLA (polylactide ) in DCM ( dichloro methane) and precipitating the catalyst using deionized water.
BRIEF DESCRIPTION OF THE DRAWINGS
Scheme 1 describes Synthesis of zinc prolinate catalysts Figure 1 depicts X-ray structure of zinc-proline complex
Figure 2 depicts the characterization of recrystallized Zinc prolinate catalyst by solid state Cp/mass 13C NM (Cross polarization/magic angle spinning) at 500MHz. Peak at 172 shows trace amounts of Zinc acetate, peak at 176.34 corresponds to carboxylic acid group present in L-proline not coordinated with Zinc, while the peak at 178.60 corresponds to carboxylic acid coordinated with Zinc.
Figure 3 depicts 1- 13C quantitative NMR spectra (500 MHz) of sample PLA-4.The absence of a split carbonyl peak at 169.0 clearly shows that polymer is single isomer and proves that absence of racemisation of polymer by the process disclosed.
Figure 4 depicts Size Exclusion Chomatography elugram of PLA-4.SEC graph of PLA-7, from which the Mw has been calculated to be 100500.
Figure 5 depicts differential scanning calorimetry (DSC) thermogram of PLA-4.The DSC curve was obtained using Perkin Elmer instrumentation. The sample was heated from -405C to 2009C at the rate of 109C/minute under nitrogen atmosphere. Then it was held for 1 minute and cooled suddenly at the rate of lOO^C/minute. The sample is again heated from -409C to 2009C at the rate of 109C/minute. Tm and Tg values were calculated from first and third heating curves respectively. The DSC clearly shows the presence of a single isomer,! isomer of polylactide.
DETAILED DESCRIPTION OF THE INVENTION
The invention will now be described in detail in connection with certain preferred and optional embodiments, so that various aspects thereof may be more fully understood and appreciated.
The present invention provides a one pot process for the synthesis of high molecular weight polylactide using a non toxic catalyst which is readily recoverable. The inventive process provides stereo selective polylactide without racemization.
High molecular weight polylactic acid was prepared from lactide by ring opening polymerization.
The divalent metal of the catalyst is selected from a group comprising (Group II) elements such as Be, Mg, Ca, Sr, Ba, Ra and transitional and inner transitional metals such as V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Mo, Rh, Pd, Ag, Cd, W, Re, Os, Ir, Pt, Hg, Sm, Eu, Tm, Yb and the acid is selected from the group comprising amino acids and hydroxyl carboxylic acids. The amino acids are aliphatic, alicyclic or aromatic. The most preferred catalyst of the invention is Zinc prolinate. In a preferred embodiment the catalyst employed is synthesized by stirring Zinc acetate (1 equiv.), L-proline (2 equiv.) and triethylamine (2 equiv.) in methanol. The complex is precipitated out from the methanolic solution and isolated.
The one pot process of the invention for the preparation of high molecular weight polylactide by ring-opening polymerization of Lactides (L,L- D,D- D,L- and meso) is carried out at a constant temperature in an inert atmosphere. The requisite amount of lactide and freshly recrystallized catalyst are taken in silanized glass reactor. At the beginning the desired reaction temperature is set, the quartz reactor containing the reaction mixture is kept in the reactor chamber. After the completion of the reaction, the product is cooled under inert atmosphere.
The product was used for further characterization. The optical purity ία]0 20 of PLA polymer(C=10g/L in CHCI3) was measured at 20 °C. The measured value was found 156.9 which matched the literature value 157.0 (100% optical purity)
The catalyst can be recovered by dissolving PLA in DCM and precipitating using deionised water.
The process led to pure poly I lactides (PLA) with molecular weight greater than 50,000/ as seen in table 1 even with variations in temperature in tehrange of 150-2009C. The DSC of the samples PLA 6, 6a and 7 shows the single isomer formation.
TABLE - 1
Effect of reaction time on ring opening polymerization of L,L-lactide
Figure imgf000008_0001
No. (mole ratio) (SC) (hour) (%) ( MR) (GPC) (GPC)
PLA-1 200:1 170 4 53,000 79,000 1.48
PLA-2 200:1 170 6 58,000 98,000 1.68
PLA-3 200:1 170 8 62,000 1,04,000 1.67
PLA-4 200:1 170 10 76,000 1,30,000 1.71
PLA-5 270:1 200 3 48,000 72,000 1.5
PLA-6 225:1 180 3 88 30,000 51,000 1.7
PLA-7 225:1 180 4 90 62,815 1,05,000 1.6
PLA-6a 225:1 180 5 92 24,900 42,330 1.7
PLA-8 400:1 180 4 86 36, 600 51240 1.4
Table2: Thermal Characterization of Poly (L-Lactide)s
Figure imgf000009_0001
The process may be carried out at a temperature range of 150-200, preferably 170-200 deg C. EXAMPLES
The following examples are given by way of illustration of the present invention and should not be construed to limit the scope of the present invention.
Example 1
Synthesis of zinc prolinate catalysts:
The catalyst zinc L-prolinate was synthesized by stirring zinc acetate Zri (OAc)2 (1 equiv.), L- proline (2 equiv.) and triethylamine (2 equiv.) in methanol. The complex was precipitated out from the methanolic solution and isolated. Zinc D-prolinate was prepared by using similar procedure. The crude product was recrystallized thrice from 30 ml of a water/2- propanol mixture (1:1). After drying at 60°C over P4Oi0 (phosphorus pentoxide) in vacuum, the yield was obtained as 99%.
Zinc salt of L-proline was compared with that of D-proline and found that zinc salt possessed similar structure. Zinc salts (e.g. that of L-proline and D-proline) were dried over P Oi0 prior to use and composition was checked by elemental analysis. Ci0Hi6N2O4Zn (291.60), calculated, C 40.91, H 5.48, N 9.54 and found C 40.90 H 5.53 N 9.4. This catalyst is low hygroscopic. The crude product was recrystallized and [a]D 20= -53 .68 concentration 2.59/dl in water. Recrystallization of zinc prolinate was carried out using various proportions of isopropyl alcohol and water (90:10, 80:20, 70:30, 60:40, 50:50). The best result was obtained at 50:50 compositions. The solid state 13C nmr confirmed the structure zinc prolinate. The acid group of L- or D- proline makes complex with zinc metal. Some of the acid groups of L- proline are free even using zinc acetate and L- proline in 2:1 equivalent proportion. The equivalent of zinc acetate will be varied to achieve 100% complexation without any free acid groups of L- proline.
The spectroscopic data show the mononuclear zinc (prolinate)2 derivatives to be the prevailing species.
The complex was resulted from the reaction of zinc acetate with either (L or D) proline. The two L-proline molecules are coordinated to the zinc atom via their N and carboxylic O atom. The two bidentate ligands are Trans with respect to each other. The zinc atom is pentacoordinate, fifth coordination site being occupied by the symmetry related O (4') (symmetry code: (i) 2-x, y-1/2, -z) of a neighbouring proline molecules, so that an infinite polymeric chain is generated. The polymer shows a helical structure along the 21 direction. The zinc coordination here is unique as most zinc amino acid complexes are hexadentate.
FTIR also confirmed the structure before and after the complexation with proline. FTIR showed the N-H stretching at ~3750 cm"1, C=0 ketonic (v CO) = 1590 cm"1 and antisymmetric and symmetric carbonyl stretching frequency at 1720 and 1350 cm"1.
The stretching v (CO) and v N-H bands of L-proline, after coordination with zinc, appeared at 3250 and 1550 cm"1 respectively. The antisymmetric and symmetric carbonyl stretching frequency is at 1550 and 1350 cm"1 respectively. The difference between the antisymmetric and symmetric stretching frequencies v (COO ), which is 168 cm"1 was similar to the stretching frequency of M-0 bond.
Similarly IR spectra of zinc D-prolinate showed the frequency at 3250 cm 1 and 1550 cm"1. The carbonyl antisymmetric and symmetric stretching frequencies appeared at 1680 and 1382 cm 1 respectively. Zinc prolinate was characterized by thermo gravimetric analysis (TGA) and found stable up to 371°C.
Scheme 1 describes Synthesis of zinc prolinate catalysts, while Figure 1 depicts X-ray structure of zinc-proline complex
Figure 2 depicts the characterization of recrystallized Zinc prolinate catalyst by solid state Cp/mass 13C NMR (Cross polarization/magic angle spinning) at 500MHz. Peak at 172 shows trace amounts of Zinc acetate, peak at 176.34 corresponds to carboxylic acid group present in L-proline not coordinated with Zinc, while the peak at 178.60 corresponds to carboxylic acid coordinated with Zinc.
Example 2
Ring-Opening Polymerization of Lactide
High molecular weight polylactic acid was prepared from lactide by ring opening polymerization technique. The experimental procedure is given below:
Ring-opening polymerization of Lactides (L,L- D,D- D,L- and meso)was carried out at a 150-
2009C under the flow of inert atmosphere (INOX Argon). The requisite amount of lactide and freshly recrystallized zinc prolinate catalyst were taken in silanized glass reactor. At the beginning the desired reaction temperature as indicated herein was set, the quartz reactor containing the reaction mixture was kept in the reactor chamber. After the completion of the reaction, the product was cooled under Argon atmosphere. The product was used for further characterization. The optical purity [a]D 20 of PLA polymer(C=10g/L in CHCI3) was measured at 20 °C. The measured value was found 156.9 which match the literature value
157.0 (100% optical purity) of L isomer of Poly (L) lactide. This catalyst can also be recovered by dissolving PLA in DCM and precipitating using deionized water because that is in water soluble.
Example 3
The poly L lactide thus formed in accordance to example 2, PLA 7 was characterized by 13C NMR. Figure 3 depicts 1- 13C quantitative NMR spectra (500 MHz) of sample PLA-4.The absence of a split carbonyl peak at 169.0 clearly shows that polymer is single isomer and proves that absence of racemisation of polymer by the process disclosed.
Example 4
Figure 4 depicts Size Exclusion Chomatography elugram of PLA-4., from which the Mw has been calculated to be 1,30,000.
Example 5
Figure 5 depicts differential scanning calorimetry (DSC) thermogram of PLA-6, 6a and 7.The DSC curve was obtained using Perkin Elmer instrumentation. The sample was heated from - 409C to 2002C at the rate of 10eC/minute under nitrogen atmosphere. Then it was held for 1 minute and cooled suddenly at the rate of lOO^C/minute. The sample is again heated from - 409C to 2009C at the rate of lO^C/minute. Tm and Tg values were calculated from first and third heating curves respectively. The DSC clearly shows the presence of a single isomer, L isomer of polylactide. '
Advantages of the present invention
1. Pure isomer obtained 2. Solvent free process
3. Catalyst can be recovered
4. High molecular weight of polymer obtained.

Claims

1. One pot solvent free process for preparation of high molecular weight poly L lactide comprising ring-opening polymerization of Lactides catalysed by a recrystallized form of a precursor of a divalent metal and an acidto result in poly L lactide of Mw>50,000.
2. The one pot solvent free process according to claim 1, wherein the divalent metal of the catalyst is selected from a group consisting of Be, Mg, Ca, Sr, Ba, Ra and transitional and inner transitional metals V, Cr, Mn, Fe, Co, ΝΊ, Cu, Zn, Mo, Rh, Pd, Ag, Cd, W, Re, Os, Ir, Pt, Hg, Sm, Eu, Tm, Yb.
3. The one pot solvent free process according to claim 1, wherein the acid is selected from the group consisting of amino acids and hydroxyl carboxylic acids.
A. The one pot solvent free process according to claim 3, wherein the amino acids are selected from the group consisting of aliphatic, alicyclic or aromatic.
5. The one pot solvent free process according to claim 1, wherein the catalyst is recrystallized Zinc prolinate.
6. The one pot solvent free process according claim 1, wherein the process is carried out at a temperature in the range of 180-200°C in an inert atmosphere.
7. The one pot solvent free process according to claim 1, wherein the molar ratio of polylactide to Zinc prolinate is in the range of 200: 1 to 400:1.
8. The one pot solvent free process according to claim 1, wherein the catalyst is recovered by dissolving PLA (polylactide ) in DCM ( dichloro methane) and precipitating the catalyst using deionized water.
PCT/IN2013/000033 2012-01-17 2013-01-17 A solvent free process for preparation of high molecular weight polylactide catalyzed by a compound of a divalent metal and an acid resulting in corresponding stereo selective polylactide WO2013108271A1 (en)

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