THF coordinated monomeric group 13 metal alkoxide adducts, synthesis and catalytic activity thereof

Abstract

The present invention discloses monomeric THF coordinated Group 13 metal alkoxides, synthesis and catalytic activity thereof The method of synthesis of monomeric THF coordinated Group 13 metal alkoxides (formula I) described in the present invention yields alkyl alcohol adducts of Group 13 metal (Aluminum, Gallium, and Indium) alkoxides have their fourth coordination satisfied. The catalytic activity of the Group 13 metal alkoxide adduct compounds is useful for the ring opening polymerization (ROP) of compounds such as racemic lactide to yield PLA. These Group 13 metal alkoxide adducts initiate polymerization under milder reaction conditions as compared to tin octanoate and thus can serve as catalyst for synthesis of polymers like PLA,Polycaprolactone with 10 high molecular weight.

Description

[0001]DESCRIPTION TITLE OF THE INVENTION: THF Coordinated Monomeric Group 13 Metal Alkoxide Adducts, Synthesis and Catalytic Activity Thereof FIELD OF THE INVENTION The present invention is related to monomeric THF coordinated group 13 metal alkoxides, synthesis and catalytic activity thereof. More specifically, the method of synthesis of monomeric THF coordinated Group 13 metal alkoxides described in the present invention yields alkyl alcohol adducts of Group 13 metal (Aluminum, Gallium, and Indium) alkoxides have their fourth coordination satisfied. The catalytic activity of the Group 13 metal alkoxide adduct compounds is useful for the ring-opening polymerization (ROP) of compounds such as racemic lactide to yield PLA. BACKGROUND OF THE INVENTION The Group 13 metal isopropoxide can be metal precursors in various organic and organometallic transformations. It is challenging to isolate M(III) (M = Al, Ga, In) isopropoxide in its monomeric state as a tricoordinate metal center tends to oligomerize to fulfill its fourth coordination site. The literature reported to date for the synthesis of Group 13 metal isopropoxide mainly relies on either direct addition of isopropyl alcohol to benzene solution of metal chlorides for aluminum or salt metathesis reaction of Group 13 metal chlorides with alkali-metal alkoxides for gallium and indium. Tetrahydrofuran (THF) (CAS 109-99-9) is a is a colorless, stable and a volatile liquid ,has a acetone like smell. It is miscible in water and most organic solvents. It is useful for manufacture of various chemicals in pharmaceutical, agricultural and other industrial synthesis domains. Being a versatile solvent, and a Lewis base it can coordinate to various metal ions. Synthesis of group 13 metal alkoxides is desired such that they are economically synthesized in high yields and easily isolated, with minimal or no impurities. The current invention discloses the synthesis of group 13 metal alkoxides using metal halide precursors and alkyl alcohols. The synthesized alkyl alcohol adducts of Group 13 metal (aluminum, gallium, and indium) alkoxides have their fourth coordination satisfied by the method described herewith. Moreover, there’s no chlorine contamination and isolating the synthesized metal alkoxide adduct is easier. The synthesized Group 13 metal alkoxide adduct are useful for the ring-opening polymerization (ROP) of rac-LA (racemic lactide) as they act as efficient initiators of ring-opening polymerization (ROP) of rac-lactide, enable synthesis of high molecular weight PLA. SUMMARY One aspect of the current invention is a method of synthesizing a monomeric THF coordinated metal alkoxide adduct, the method comprising the steps of; a. Reacting a corresponding metal halide with THF in an inert gas medium to obtain a reaction mixture followed by addition of a solvent; b. Addition of an alkyl alcohol to the reaction mixture in step a. to obtain the monomeric THF coordinated metal alkoxide adduct; wherein the metal is selected from Aluminium, Gallium or Indium and wherein ratio of the metal halide to alkyl alcohol is 1:3 to 1:5 In one aspect, the halide is chloride. In one aspect the alkyl alcohol is a C2-C20 alcohol. In one aspect the alkyl alcohol is isopropyl alcohol. In one aspect ,THF is added in an equimolar ratio to the metal halide. In one aspect the ratio of the metal halide to the alkyl alcohol is 1:4. In one aspect the inert gas is argon.In one aspect the solvent in step a) is toluene. In one aspect step b) comprises refluxing the reaction mixture at 80-110°C for 10-15 hours. In one aspect the obtained monomeric THF coordinated metal alkoxide adduct in step b) is free of chlorine contamination. One aspect of the invention is a compound of the formula I made by the method encompassed in the invention wherein M is selected from Aluminium, Gallium or Indium and wherein the “R-OH” is an alkyl alcohol. In one aspect the alkyl alcohol is isopropyl alcohol. Another aspect of the invention is a method of making polylacticacid (PLA), wherein the method comprises the steps of ; i.adding compound of formula I to rac-LA in a reaction vessel followed by stirring at temperature range of 55-80°C wherein the polymerization occurs in a solvent to obtain a crude PLA ii.removing the solvent in step i. followed by precipitating the crude PLA to obtain precipitated PLA; iii.isolating the precipitated PLA .In one aspect the molar ratio of rac-LA to compound of formula I is 200:1. In one aspect the compound of formula I is a THF coordinated isopropoxide isopropanol adduct. In one aspect the synthesized polylactic acid (PLA) has a molecular weight in the range of 70-150 KDa Brief Description Of Figures: Fig 1. illustrates the1H NMR (500 MHz, CDCl3) of Al(OiPr)3.THF.iPrOH Fig 2. illustrates 13C NMR (125 MHz, CDCl3) of Al(OiPr)3.THF.iPrOH Fig 3. illustrates HRMS (High-resolution mass spectrometry ) Spectrum of Al(OiPr)3.THF.iPrOH Fig 4. illustrates DOSY (Diffusion-ordered spectroscopy) NMR spectrum (500 MHz, CDCl3) of Al(OiPr)3.THF.iPrOH Fig 5. illustrates1H NMR (500 MHz, CDCl3) of Ga(OiPr)3.THF.iPrOH Fig.6. illustrates13C NMR (125 MHz, CDCl3) of Ga(OiPr)3.THF.iPrOH Fig 7. illustrates HRMS Spectrum of Ga(OiPr)3.THF.iPrOH Fig.8. illustrates DOSY NMR spectrum (500 MHz, CDCl3) of Ga(OiPr)3.THF.iPrOH . Fig.9. illustrates1H NMR (500 MHz, CDCl3) of In(OiPr)3.THF.iPrOH Fig.10. illustrates13C NMR (125 MHz, CDCl3) of In(OiPr)3.THF.iPrOH Fig.11. illustrates DOSY NMR spectrum (500 MHz, CDCl3) of In(OiPr)3.THF.iPrOH Fig.12. illustrates HRMS Spectrum of In(OiPr)3.THF.iPrOH Fig.13. illustrates the formula of THF coordinated Group 13 metal alkoxides of formula (I) DETAILED DESCRIPTION OF THE INVENTION In the following detailed description, a reference is made to the accompanying drawings that form a part hereof, and in which the specific embodiments that may be practiced is shown by way of illustration. These embodiments are described in sufficient detail to enable those skilled in the art to practice the embodiments and it is to be understood that other changes may be made without departing from the scope of the embodiments. The following detailed description is therefore not to be taken in a limiting sense. The current invention encompasses THF coordinated group 13 metal alkoxide compounds in their monomeric form, method of synthesizing THF coordinated group 13 metal alkoxides and catalytic activity of group 13 monomeric metal alkoxides in synthesizing polymers including PLA, with high molecular weight. Group 13 metal alkoxides have been synthesized by many prior methods, however the synthesized metal alkoxides have a tendency to oligomerize. According to equation 1 shown below for the production of one mole gallium alkoxide theoretically the starting materials must be one mole of gallium chloride and three moles of sodium alkoxide. GaCl3 + 3NaOR Ga(OR)3 + 3NaCl But practically the products obtained by using three equivalents of sodium alkoxide is shown by equation 2 GaCl3 + 3NaOR NaGaCl(OR)3 + 2NaCl The above product arises in order to satisfy the coordination requirement of the central metal atom. The major disadvantage is that product is contaminated by the presence of chlorine. The contamination due to chlorine can be eliminated by the reaction of gallium chloride with more equivalent of sodium alkoxide as shown by equation 3 GaCl3+ 4NaOR NaGa(OR)4+ 3NaCl The contamination due to sodium is still present. The problem due to sodium contamination was overcome by using barium and strontium alkoxide for the reaction in place of alkali metal alkoxide as shown by equation 4 (a) and 4 (b) (4a) GaCl3 + 2Ba(OR)2 ½ Ba[Ga(OR)4]2 + ½ BaCl2 (4b) ½ Ba[Ga(OR)4]2 Ga(OR)3 + ½ Ba(OR)2 (4b) The product obtained is free chlorine contamination and Ba(OR)2needs to be removed. The method described in the current invention synthesizes aluminum, gallium and indium isopropoxide adducts starting from corresponding metal halides and isopropanol. The objective of this process is to satisfy the fourth coordination of the metal using THF. As THF is a coordinating solvent and Group 13 metals are sufficiently hard centers , thus THF can occupy the fourth coordination site. The possibility of chlorine contamination is minimum as the byproduct is HCl gas. Thus synthesis of the alkoxides was possible by the introduction of THF in the reaction medium which occupies the fourth coordination site around metal. Advantages of the Invention: • The synthesized THF coordinated Group 13 metal alkoxides exists in monomeric state and thus cracking is not required. Catalytic reactions can be performed under mild conditions. • The Group 13 based catalyst have less toxicity associated with them. • The synthesis of polymers like PLA from rac-LA, synthesis of polycaprolactone • The polymerization is performed under comparatively mild reaction conditions as compared to tin octanoate and thus can serve as potential catalyst for synthesis of PLA industrially. • The molecular weight of the PLA obtained is high (more than 1lakh Daltons). The polymers including PLA, obtained using group 13 metal alkoxides in monomeric form as catalysts have atactic nature. The atactic PLA can serve as good polymer for packaging. DEFINTIONS: The term “group 13 metal alkoxides” as used herein are group 13 metal alkoxide compounds and include metal alkoxide adducts of corresponding alkyl alcohols. Group 13 metal includes Aluminum (Al) , Indium (In) , Gallium (Ga). The term “alkyl alcohol” refers to a group of alcohols that are aliphatic alcohols and include iso alcohols like isopropyl alcohol. As used herewith “racemic lactide” or “racemic LA” refers to composed of dextrorotatory and laevorotatory forms of a Lactide compound in equal proportion. Lactide (3,6-dimethyl-1,4-dioxane- 2,5-dione) (CAS : 95-96-5) is a cyclic ester , used as a monomer for production of polylactic acid (PLA). As used herewith the term Polydispersity Index or “PDI” of a polymer is calculated as the ratio of weight average by number average molecular weight. PDI value helps for improved selection of polymers for an application. For monodisperse polymers have the PDI value as 1. Step-growth polymerization reactions typically yield values of Mw / Mn of around 2.0 and chain- growth polymerization yield Mw / Mn values in the range of 1.5–20. As used herewith “Ring-opening polymerization (ROP)” is a form of chain-growth polymerization where the terminus of a polymer chain attacks cyclic monomers to form a longer polymer. The reactive center can be radical, anionic or cationic. ROP continues to be the most versatile method of synthesis of major groups of biopolymers, particularly when they are required in quantity. EMBODIMENTS The current invention encompasses a method of making a monomeric THF coordinated metal alkoxide adduct, monomeric THF coordinated metal alkoxide adducts, their application in making high molecular weight polymers such as poly lactic acid. One embodiment of the current invention is a method of synthesizing a monomeric THF coordinated metal alkoxide adduct, the method comprising the steps of; a) Reacting a corresponding metal halide with THF in an inert gas medium to obtain a reaction mixture followed by addition of a solvent; b) Addition of an alkyl alcohol to the reaction mixture in step a. to obtain the monomeric THF coordinated metal alkoxide adduct; wherein the metal is selected from Aluminium, Gallium or Indium and wherein ratio of the metal halide to alkyl alcohol is 1:3 to 1:5. In one embodiment, the ratio of metal halide to the alkyl alcohol is 1:4. In one embodiment the halide is chloride. In one embodiment, the metal halide is Aluminium chloride (AlCl3). In one embodiment, the metal halide is Indium chloride (InCl3). ). In one embodiment, the metal halide is Gallium chloride (GaCl3). In one embodiment the alkyl alcohol is a C2-C20 alcohol. In one embodiment the C2-C20 alcohol is selected from ethanol, isopropyl alcohol, butanol , isobutanol or pentanol. In one embodiment the alkyl alcohol is isopropyl alcohol. In one embodiment the THF compound is added in an equimolar ratio to the metal halide. In one embodiment, THF was dried over sodium benzophenone before reacting with the metal halide in step a. In one embodiment the reaction mixture of THF and metal halide was stirred for 10-15 minutes at a temperature of range of 22-35 °C. In one embodiment the reaction mixture of THF and metal halide was stirred for 10 minutes at a temperature of range of 25-30 °C. In one embodiment the inert gas is argon. In one embodiment the solvent in step a) is selected from xylene, ethyl benzene or toluene. In one embodiment the solvent in step a) is toluene. In one embodiment, the solvent was added to the reaction mixture comprising the metal halide, THF followed by stirring for 15-30 minutes. In one embodiment the solvent was toluene. In one embodiment toluene was dried over sodium benzophenone before adding to the reaction mixture comprising the metal halide and THF. In one embodiment, the alkyl alcohol was added after stirring the reaction mixture with the solvent. In one embodiment, the addition of alkyl alcohol is in inert conditions. In one embodiment step b) comprises refluxing the reaction mixture at 80-110°C for 10-15 hours. In one embodiment, the reaction mixture was refluxed at 90 °C in step b) for 12 hours. In one embodiment the obtained monomeric THF coordinated metal alkoxide in step b) is free of chlorine contamination. One embodiment of the invention is a monomeric tetrahydrofuran (THF) coordinated metal alkoxide adduct of formula I , wherein M is selected from Aluminium, Gallium or Indium and wherein the R-OH group is an alkyl alcohol. In one embodiment of the invention is the compound of the formula I is made by the method encompassed in the invention, wherein M is selected from Aluminium, Gallium or Indium and wherein the “R-OH” is an alkyl alcohol. In one embodiment the alkyl alcohol in formula I is selected from isopropanol, butanol, isobutanol, pentanol. In one embodiment the alkyl alcohol is isopropyl alcohol. In one embodiment, the compound of formula I is a THF coordinated Aluminium isopropoxide isopropanol adduct. In one embodiment, the compound of formula I is THF coordinated Indium isopropoxide isopropanol adduct. In one embodiment, the compound of formula I is THF coordinated Gallium isopropoxide isopropanol adduct. One embodiment of the invention is a method of making poly lactic acid (PLA), wherein the method comprises the steps of ; i. adding compound of formula I to rac-LA in a reaction vessel followed by stirring at temperature range of 55-80°C wherein the polymerization occurs in a solvent to obtain a crude PLA. ii. removing the solvent in step i. followed by precipitating the crude PLA to obtain precipitated PLA; iii. Isolating the precipitated PLA . In one embodiment, crude PLA comprises polylactic acid along with low molecular weight oligomers. In one embodiment the compound of formula I is a group 13 metal alkoxide adduct wherein the metal is selected from Aluminium, Gallium or Indium. In one embodiment, the stirring in step i. was done at a temperature of 70°C. In one embodiment the solvent in step i. is THF. In one embodiment the reaction in step i. occurs in an inert atmosphere. In one embodiment the molar ratio of rac-LA to compound of formula I is 200:1. In one embodiment the compound of formula I is a THF coordinated isopropoxide isopropanol adduct. In one embodiment, progress of polymerization in step i. is traced by recording the1H NMR spectra of aliquots taken from the reaction mixture in step i. periodically. In one embodiment the solvent is removed under vacuum. In one embodiment the crude PLA obtained in step i. is dissolved in dichloromethane followed by pouring in cold methanol to precipitate the poly lactic acid in step ii. In one embodiment the precipitated PLA is isolated by drying over a vacuum in step iii. In one embodiment, vacuum drying was done for 8-10 hours. In one embodiment the synthesized Poly lactic acid (PLA) has a molecular weight in the range of 70-150 KDa. In one embodiment the synthesized Poly lactic acid (PLA) has a molecular weight in the range of 105-125 KDa. In one embodiment, the group 13 metal alkoxide adducts synthesized by the method encompassed in the invention can initiate the ring-opening polymerization of compounds such as racemic lactide, ε-caprolactone, glycolide, , trimethylene carbonate, lactones, cyclic anhydrides. The foregoing description of the specific embodiments willfully reveal the general nature of the embodiments herein that others can, by applying current knowledge, readily modify and / or adapt for various applications such as specific embodiments without departing from the generic concept, and, therefore, such adaptations and modifications should and are intended to be comprehended within the meaning and range of equivalents of the disclosed embodiments. It is to be understood that the phraseology or terminology employed herein is for the purpose of description and not of limitation. Therefore, while the embodiments herein have been described in terms of preferred embodiments, those skilled in the art will recognize that the embodiments herein can be practiced with modifications. However, all such modifications are deemed to be within the scope of the claims. The scope of the embodiments will be ascertained by the claims to be submitted at the time of filing a complete specification. EXAMPLES Example 1: Synthesis of group 13 metal isopropoxide salts Inside an argon-filled glovebox, a Schlenk flask equipped with a magnetic stirrer, neat group 13 metal chloride salts [AlCl3(500 mg, 0.0037 mol), GaCl3(500 mg, 0.0028 mol), InCl3(500 mg, 0.0023 mol)] and THF (dried over sodium benzophenone) was added [0.30mL (0.0037 mol) for AlCl3, 0.23mL (0.0028 mol) for GaCl3, and 0.19mL (0.0023 mol) for InCl3] and stirred for 10 minutes at room temperature. After 10 minutes 5 mL of toluene (dried over sodium benzophenone) added to the THF. MCl3(M = Al, Ga, In) solution. The mechanical stirring was continued for more 20 minutes at room temperature and after that Isopropyl alcohol [1.12mL (0.0148 mol) for AlCl3, 0.84mL (0.0112 mol) for GaCl3, and 0.68mL (0.0092 mol) for InCl3] was added in an inert condition. The mixture was stirred and refluxed at 90oC for 12h. After 12h the solvent was removed in vacuum and dried for 12-14h. The synthesized products were characterized by1H,13C, DOSY NMR, and Mass Spectrometry (Figure S1-S12). Table1 Group 13 Metal THF (mol) Isopropyl Yield (%) Metal Chloride alcohol (mol) Salts (mol) Al 0.0037 0.0037 0.0148 76.47 Ga 0.0028 0.0028 0.0112 68.11 In 0.0023 0.0023 0.0092 52.24 Example 2: Ring Opening Polymerization (ROP) of rac-LA 0.034 mmol of M(OiPr)3.THF.iPrOH (M = Al, Ga, In), 1 g rac-LA (200:1 ratio of rac-LA and M(OiPr)3.THF.iPrOH) THF (5 mL) were taken in a dry glass reaction tube equipped with a magnetic stirrer under an argon atmosphere. The contents were rapidly stirred at 70 °C in THF. The progress of polymerization was traced by recording the1H NMR spectra of aliquots taken from the reaction mixture periodically. The solvent was removed under vacuum. The crude was dissolved in a minimum quantity dichloromethane (CH2Cl2) and poured into cold methanol (5 mL). The polymer was precipitated and isolated by filtration. The filtered product was dried in a vacuum for 8-10 h. Table 2. Polymerization data for rac-LA using group 13 metal precursor as catalysts in the ratio 200:1 at 70 °C in THF. Entry Catalyst Time(min)aConversion Mn(Expt)cMw / Mn (PDI) (%)b c1 Al 14 99 74,748.66 1.10 2 Ga 19 99 91,431.78 1.09 3 In 28 98 1,06,468.86 1.09aTime of polymerization measured by quenching the polymerization reaction at maximum conversion.bCalculated from1H NMR spectrum.cMeasured by GPC at 40 °C in THF relative to polystyrene standards with Mark–Houwink corrections; MnExpt= 0.58 MnGPCfor rac-LA.

Claims

We claim:

1. A method of synthesising a monomeric tetrahydrofuran (THF) coordinated metal alkoxide adduct, the method comprising the steps of; a) Reacting a corresponding metal halide with THF in an inert gas medium to obtain a reaction mixture followed by addition of a solvent; b) Addition of an alkyl alcohol to the reaction mixture in step a) to obtain the monomeric THF coordinated metal alkoxide adduct; wherein the metal is selected from Aluminium, Gallium or Indium and wherein ratio of the metal halide to alkyl alcohol is 1:3 to 1:5 2. The method of claim 1 wherein the halide is chloride.

3. The method of claim 1 wherein the alkyl alcohol is a C2-C20 alcohol.

4. The method of claim 1 wherein the alkyl alcohol is isopropyl alcohol.

5. The method of claim 1 wherein THF is added in an equimolar ratio to the metal halide.

6. The method of claim 1 wherein the ratio of the metal halide to the alkyl alcohol is 1:

4.

7. The method of claim 1 wherein the inert gas is argon.

8. The method of claim 1 wherein the solvent in step a) is toluene.

9. The method of claim 1 wherein step b) comprises refluxing the reaction mixture at 80- 110°C for 10-15 hours.

10. The method of claim 1 wherein the obtained monomeric THF coordinated metal alkoxide in step b) is free of chlorine contamination.

11. A monomeric tetrahydrofuran (THF) coordinated metal alkoxide adduct of formula I ,I wherein M is selected from Aluminium, Gallium or Indium and wherein the R-OH group is an alkyl alcohol.

12. The compound of claim 11, wherein the compound is a group 13 metal alkoxide adduct.

13. The compound of claim 11, wherein the alkyl alcohol is a C2-C20 alcohol 14. The compound of claim 11, wherein the alkyl alcohol is isopropanol, butanol, isobutanol or pentanol.

15. The compound of claim 11, wherein the alkyl alcohol is isopropanol.

16. The compound of claim 11, wherein the compound is a THF coordinated Aluminium isopropoxide isopropanol adduct.

17. The compound of claim 11, wherein the compound is a is THF coordinated Indium isopropoxide isopropanol adduct.

18. The compound of claim 11, wherein the compound is a THF coordinated Gallium isopropoxide isopropanol adduct.

19. The compound of claim 11, wherein the compound is an efficient initiator of ring-opening 5 polymerization (ROP) of rac-LA (racemic lactide) to form poly lactic acid.

20. A method of making poly lactic acid (PLA), wherein the method comprises the steps of ; i. adding compound of formula I to rac-LA in a reaction vessel followed by stirring at temperature range of 55-80°C wherein the polymerization occurs in a solvent to obtain a crude PLA ii. Removing the solvent in step i. followed by precipitating the crude PLA to obtain precipitated PLA; iii. Isolating the precipitated PLA 21. The method of claim 20, wherein the molar ratio of rac-LA to compound of formula I is 200:

1.

22. The method of claim 20, wherein the compound of formula I is a THF coordinated isopropoxide isopropanol adduct.

23. The method of claim 20, wherein the synthesized Poly lactic acid (PLA) has a molecular weight in the range of 70-150 KDa

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