Classifications

• • 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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• 2013
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