WO2000077072A1

WO2000077072A1 - Soluble polyfunctional initiators for lactone ring-opening polymerization

Info

Publication number: WO2000077072A1
Application number: PCT/US2000/015900
Authority: WO
Inventors: Lee Arnold Schechtman; Joseph Jay Kemper
Original assignee: Procter and Gamble Co
Current assignee: Procter and Gamble Co
Priority date: 1999-06-11
Filing date: 2000-06-09
Publication date: 2000-12-21
Anticipated expiration: 2001-12-11
Also published as: AU5731000A

Abstract

A substantially homogeneous composition is produced by mixing a polyhydric alcohol, an organic zinc compound having two organic groups and a solvent.

Description

SOLUBLE POLYFUNCTIONAL INITIATORS FOR LACTONE

RING-OPENING POLYMERIZATION

TECHNICAL FIELD

This invention relates to soluble polyfunctional initiators for lactone ring- opening polymerization. More particularly, the invention relates to substantially soluble initiators produced by the addition of polyhydric alcohols to organic zinc compounds having two organic groups and to lactone polymers formed with such initiators.

BACKGROUND ART

Organozinc catalysts have been used in the production of polymers by ring-opening polymerization of β-substituted-β -lactones. Unfortunately, these systems often have negative characteristics, such as requiring long reaction times, producing low yields of polymer, producing polymers of either low molecular weight or with a broad molecular weight distribution, or producing mixtures of isotactic, atactic, and/or syndiotactic polymers.

Zhang, et al., Macromolecules, 23, 3206-3212 (1990), and Tanahashi, et al., Macromolecules, 24, 5732-5733 (1991 ), disclose polymerization of β-substituted-β-propiolactones with dialkylzinc-water initiators. The polymerization is carried out for 5 days at a temperature of 60°C. Yields of polymer are generally 57-84%, but can reach 100% when using racemic β-butyrolactone. The polyesters have molecular weights of up to 50,000, with polydispersities of typically 1.1-1.5. Unfortunately, the nature of the initiator is not well defined and the actual monomer-initiator ratio used is hard to quantitate. Le Borgne et al., Polymer, 30, 2312-2319 (1989), disclose the use of polymerization initiators prepared by reacting diethyl zinc and chiral alcohols or glycols, and exemplify the use of diethylzinc-[R]-(-)-3,3-dimethyl-1 ,2-butanediol to initiate the polymerization of racemic β-butyrolactone in bulk. The diethylzinc- [R]-(-)-3,3-dimethyl-1 ,2-butanediol initiator of Le Borgne et al. is a white solid. The reaction times are short, 2.5-15 hours, and the yield can be as high as 84%. However, the polyesters have low molecular weights, generally up to about 20,000.

Barakat et al., Macromolecules, 24, 6542-6545 (1991 ), disclose polymerization of e-caprolactone using zinc mono- and dialkoxide initiators. The initiators are prepared by reacting diethyl zinc with 2-bromoethanol or 4-penten- 1-ol. The polyesters have low molecular weights, generally up to about 5,550.

Bero et al., Makromol Chem., 194, 907-912 (1993) disclose the use of ethylzinc isopropoxide to copolymerize e-caprolactone and L,L-lactide. The copolymers thus formed have molecular weights in the range of from 50,000 to 125,000, and polydispersities of from about 1.2 to about 1.4. These polymerizations are carried out for from 60 to 605 hours at temperatures of from 50° C to 100° C.

Reichle, U.S. Patent No. 4,667,013, discloses polyalkylene oxides produced by polymerization of cyclic oxides in contact with a catalyst comprising the reaction product of a dihydrocarbyl zinc compound and a linear alkanediol in contact with a silica dispersion aid and a nonionic surfactant in an inert diluent. Reichle exemplifies a catalyst composition which is a dispersion of fine solid particles.

Fujikake et al., U.S. Patent No. 5,326,852, discloses a method of producing alkylene oxide polymers comprising reacting an alkylene oxide in an inert hydrocarbon solvent in the presence of a catalyst. Fujikake et al. teach that the catalyst is obtained by applying a heat treatment of from about 80 to 200° C for 5 to 180 minutes to the product obtained by reacting an organic zinc compound with particular aliphatic polyhydric alcohols and monohydric alcohols. Fujikake et al. exemplify a catalyst which is a white, turbid, slightly viscous liquid. Hori et al., U.S. Patent No. 5,516,883, disclose a biodegradable copolymer formed by ring-opening copolymerization of lactones. Hori et al. disclose that suitable catalysts include tin compound catalysts such as dibutyltin oxide, tin dioctylate and dibutyltin dilaurate; zinc compound catalysts such as diethylzinc-water, diethylzinc-ethylene glycol, diethylzinc-methanol and diethylzinc-ethanol; aluminum compound catalysts, such as triethylaluminum- water, methylalumoxane, ethylalumoxane, aluminum trimethoxide, aluminum triethoxide, aluminum triisopropoxide and aluminum triphenoxide; and distannoxane catalysts such as 1 ,3-dichlorotetrabutyldistannoxane, 1-hydroxy-3- chlorotetrabutyldistannoxane, 1-hydroxy-3-(isothiocyanato)tetrabutyl- distannoxane, 1-phenoxy-3-bromotetrabutyl-distannoxane.

Schechtman et al., U.S. Patent No. 5,648,452, incorporated herein by reference, discloses a method of preparing a polyester comprising polymerizing at least one β-substituted-β-propiolactone in the presence of an initiating amount of alkylzinc alkoxide. The alkylzinc alkoxide initiator taught in Schechtman et al has the structure:

R¹ZnOR² wherein R¹ and R are independently a CM_O alkyl. Schechtman et al. teach that the polymer is produced in high yields and with low polydispersity. Schechtman et al characterize the polymer product as having weight average molecular weights of up to about 345,000.

Kumatani, JP 08-003,294, discloses reacting a dialkyl zinc, such as diethyl zinc, and a diol, such as 1 ,4-butanediol, wherein the mole ratio of diol to dialkyl zinc is equal to or greater than the stoichiometric ratio. Kumatani teaches that the polymerization of -butyrolactone with the reaction product of 1 ,4-butanediol and diethyl zinc results in polymers having a number average molecular weight of from about 2,100 to about 13,000. Unfortunately, certain diols, including 1 ,4- butanediol, form heterogenous compositions when mixed with dialkyl zinc.

It is desirable that polymerization initiators be in the form of homogenous liquids for easy handling and be soluble in the reaction medium for promotion of uniform initiation of polymerization. Many conventional initiators employed in prior art reactions are disadvantageous in that they form heterogeneous mixtures which are difficult to quantify in use. Additionally, heterogeneous initiators can cause slow and nonuniform initiation during polymerization. Therefore, there is a need for an initiator composition which is a homogenous liquid.

Biodegradable polymers of high weight average molecular weight, such as at least about 100,000, preferably at least about 500,000, are desirable for purposes such as preparing films. Unfortunately, the use of many conventional lactone right-opening polymerization initiators results in polymers with a weight average molecular weight of less than 100,000. Therefore, there is a need for an initiator which can be used to synthesize polymers with a weight average molecular weight of at least about 100,000.

Biodegradable polymers having a low polydispersity index, i.e. less than about 2, may be desired for some applications. Unfortunately, the use of many conventional lactone right-opening polymerization initiators, such as tin compound catalysts, results in polymers having a polydispersity index of about 2 or more. Therefore, there is a need for an initiator which can be used to synthesize polymers having a low polydispersity index.

SUMMARY OF THE INVENTION

Accordingly, it is the object of this invention to obviate various problems with the prior art.

It is an additional object of this invention to provide a homogeneous composition capable of initiating lactone ring-opening polymerization.

It is also an object of this invention to improve the ease of handling lactone ring-opening polymerization initiators. It is another object of this invention to produce high molecular weight polymers by lactone-ring opening polymerization.

It is a further object of this invention to produce polymers having a low polydispersity index.

In accordance with one aspect of the present invention, novel compositions are produced by mixing a polyhydric alcohol, an organic zinc compound having two organic groups and a solvent, wherein the composition is substantially homogeneous.

In accordance with another aspect of the present invention, novel methods of forming substantially homogenous initiator compositions comprise the step of forming compositions comprising polyhydric alcohol, organic zinc compound having two organic groups and solvent.

In accordance with another aspect of the present invention, novel methods of forming polymers comprise the steps of: a) mixing polyhydric alcohols and organic zinc compounds having two organic groups and solvent to form initiator compositions; b) mixing lactone monomers in the presence of the initiator compositions to form monomer mixtures; and c) heating the monomer mixtures to obtain polymers.

In accordance with another aspect of the present invention, novel zinc polyalkoxide compounds comprise a zinc-containing structure selected from the group consisting of:

R'-O R'-(OZnR)_n, I I and mixtures thereof ;

O -Zn

wherein R' is a hydrocarbyl backbone; each R is independently a Cι.₈ alkyl group, phenyl, napthyl, a Cι-₃ alkyl-substituted phenyl, a Cι-₃ alkyl-substituted napthyl, a cycloalkyl group having from about 4 to about 6 ring carbon atoms, or dicyclopentadienyl; and n is at least about 2. The zinc polyalkoxide compounds are substantially soluble in aprotic organic solvents.

It has now been found that polyfunctional zinc initiators substantially soluble in the polymerization reaction medium can be prepared. Homogeneous compositions formed by mixing polyhydric alcohols, organic zinc compounds and solvent are more easily handled and promote more uniform initiation of polymerization. It has also been found that it is possible to produce high molecular weight polymers, and polymers having a polydispersity index of less than about 2.

These and additional objects and advantages will be more fully apparent in view of the following description.

DETAILED DESCRIPTION

The present invention encompasses polyfunctional initiators, processes for preparing polyfunctional initiators, polyhydroxyalkanoate polymers, and methods of forming polyhydroxyalkanoate polymers using the polyfunctional initiators. As used herein, initiator refers to an agent used to start the polymerization of a monomer, and an initiating amount means a sufficient amount of an initiator to commence the chemical reaction for polymerization.

As used herein, all ratios are molar ratios unless otherwise specified and all percentages are by weight unless otherwise specified.

POLYFUNCTIONAL INITIATOR

As used herein, the term polyfunctional initiator refers to a compound which is capable of initiating lactone ring-opening polymerization and which has more than one oxygen atom which is bonded to a metal atom. Preferably the metal is zinc. Preferred polyfunctional initiators have two oxygen atoms which are bonded to zinc. The two oxygen atoms may each be bonded to a different zinc atom, or both oxygen atoms may be bonded to the same zinc atom.

The polyfunctional initiator is prepared by mixing a polyhydric alcohol, an organic zinc compound having two organic groups, and a solvent. As used herein, polyhydric alcohol is intended to refer to a compound having at least two hydroxyl moieties. The polyhydric alcohol has at least 2, preferably at least 3, more preferably more than 3 carbon atoms. Preferably the carbon chain of the polyhydric alcohol is branched. Preferably the polyhydric alcohol is a dihydric alcohol. In one embodiment, the polyhydric alcohol is a branched polyhydric alcohol.

Suitable polyhydric alcohols are those which when combined with a solution comprising a solvent and an organic zinc compound having two organic groups, form an initiator which is soluble in the solvent. Suitable polyhydric alcohols include 2,4-dimethyl-2,4-pentanediol, triethylene glycol, and mixtures thereof. Preferably the polyhydric alcohol is a polyhydric alcohol other than 1 ,4- butanediol, ααα'α'-tetramethyl-2,4-benzenedimethanol, 2,5-dimethyl-2,5- hexanediol, 2,5-hexanediol, bisphenol-A, or any polyhydric alcohol which forms an insoluble initiator.

The present invention is directed toward an initiator which is substantially soluble in the initiator composition solvent. As used herein, substantially soluble means that after mixing 1 1 mL of 1 .0 M organic zinc compound in solvent and 5.44 millimoles of a polyhydric alcohol having 2 hydroxyl groups to form an initiator composition, less than about 5%, preferably less than about 2%, by weight of the total initiator composition is in solid form. Preferably less than about 5%, more preferably less than about 2%, by weight, of the zinc-containing initiator which is produced is in solid form. As the initiator is substantially soluble, the initiator composition comprising the organic zinc compound, polyhydric alcohol, and solvent will be substantially homogeneous, that is less than about 5%, preferably less than about 2%, by weight of the total initiator composition, is in solid form. The solvent used in the initiator composition is one which is compatible with the lactone ring-opening polymerization reaction. Preferably the solvent is an aprotic solvent. Suitable solvents include toluene, xylenes and tetrahydrofuran. Preferably the solvents will be substantially dry, that is, the solvent comprises less than about 10 ppm water. The organic zinc compound has the structure:

RZnR wherein each R is independently a Cι-₈ alkyl group, phenyl, napthyl, a C-ι-₃ alkyl- substituted phenyl, a C-ι.₃ alkyl-substituted napthyl, a cycloalkyl group having from about 4 to about 6 ring carbon atoms, or dicyclopentadienyl. Suitable organic zinc compounds include dimethylzinc, diethylzinc, dipropylzinc, dibutylzinc, dipentylzinc, dihexylzinc, diheptylzinc, dioctylzinc, di-2-ethylhexylzinc, diphenylzinc, ditolylzinc, dicyclobutylzinc, dicyclopentylzinc, di- methylcyclopentylzinc, dicyclohexylzinc, methyl phenylzinc, methyl tolylzinc, methyl naphthylzinc, ethyl phenylzinc, and mixtures thereof.

The substantially homogeneous initiator composition may be formed by mixing a polyhydric alcohol, an organic zinc compound having two organic groups, and solvent. The molar ratio of organic zinc compound to the number of hydroxyl groups on the polyhydric alcohol is generally from about 0.5:1 to about

2:1 , preferably from about 0.5:1 to about 1.1 :1 , more preferably about 1 :1 . In one embodiment the initiator composition is formed by mixing components consisting essentially of polyhydric alcohol, organic zinc compound and solvent.

Preferably the initiator composition is substantially free of any additives which require removal and increase the need to purify the initiator, such as surfactants, monohydric alcohols, silica, or silicon-containing compounds. As used herein, substantially free of is intended to refer to less than 5%, by weight of the initiator composition.

While not being bound by theory, it is believed that the composition forms a zinc polyalkoxide compound according to the reaction. R'-(OH)_n +nZnR₂ → R'-(OZnR)_n + R'- O

O Zn

wherein R' may be any hydrocarbyl backbone, n is at least 2, and the R groups are as defined above. Preferably R' has from about 2 to about 10 carbon atoms, more preferably about 7 carbon atoms. The resulting zinc polyalkoxide may comprise one or both of the zinc-containing polyalkoxide structures set forth above. It is believed the zinc polyalkoxide forms aggregates or clusters in solution. The aggregate may comprises any number of zinc-containing structures, preferably the aggregate comprises up to about 6 zinc-containing structures. While not being bound by theory, it is believed that the major component has the structure:

R -(OZnR)n although the cyclic zinc polyalkoxide compound may also be present.

For example, it is believed that reacting 2,4-dimethyl-2,4-pentanediol and diethylzinc produces two species of initiator as shown below:

The primary initiator is believed to be: although the inventors do not intend to be bound by any theory as to the resulting compounds.

POLYMER SYNTHESIS

The zinc polyalkoxide compound is used to catalyze a lactone ring- opening polymerization. The method of forming the polymer comprises the steps of mixing a polyhydric alcohol, an organic zinc compound having two organic groups and a solvent to form a substantially homogeneous initiator composition; mixing lactone monomers in the presence of the initiator composition to form a monomer mixture; and heating the monomer mixture to obtain the polymer. Although it is not necessary to heat the initiator composition prior to addition of the lactone monomers, the initiator composition may be heated to not greater than about 50° C, preferably not greater than about 35° C, prior to addition to the lactone monomers.

As used herein, alkyl refers to a saturated carbon-containing chain which may be straight or branched and substituted (mono- or poly-) or unsubstituted; alkenyl refers to a carbon-containing chain which may be monounsaturated (i.e., one double bond in the chain) or polyunsaturated (i.e., two or more double bonds in the chain), straight or branched and substituted (mono- or poly-) or unsubstituted; and cycloalkyl refers to a cyclic alkyl (e.g., cyclohexyl), which may be substituted or unsubstituted.

As used herein, aryl refers to an aromatic moiety which may be substituted (mono- or poly-) or unsubstituted, preferably unsubstituted. Preferred aryls are phenyl and napthyl, more preferred is phenyl. As used herein, aralkyl refers to an alkyl substituted with aryl (e.g., benzyl), while alkaryl refers to an aryl substituted with alkyl (e.g., 4-methylphenyl).

As used herein, initiator refers to an agent used to start the polymerization of monomers; and an initiating ratio refers to a zinc atom:monomer molar ratio sufficient to commence the chemical reaction for polymerization. The zinc atom:monomer molar ratio is generally from about 0.01 :100 to about 10:100, preferably from about 0.02:100 to about 1 :100, more preferably from about 0.01 :100 to about 0.1 :100, that is, the mol% of zinc to monomer is generally from about 0.01 to about 10, preferably from about 0.02 to about 1 , more preferably from about 0.01 to about 0.1.

The polymer may be synthesized using any lactone capable of ring- opening polymerization. The lactone may be substituted. Suitable lactones include β-substituted-β-propiolactones, β-butyrolactone, e-caprolactone, δ- valerolactone and mixtures thereof. The process of the present invention may be carried out using a single monomer to produce a homopolymer or using a mixture of more than one monomer to produce a copolymer.

Preferred lactones are β-substituted-β-propiolactones. The β- propiolactone may be substituted at the β position by any conventional non- interfering substituent. Suitable substituents include organic residues, halo, nitro, and the like. Suitable organic residues include hydrocarbon residues which may be either unsubstituted or substituted. Suitable substituents for substituted hydrocarbon residues include halogens, nitro groups, and oxygen or sulfur- containing organic residues such as ether residues or carboalkoxy groups (-- COOR") wherein R" is an alkyl. Suitable hydrocarbon residues include alkyl, alkenyl, aryl, aralkyl, alkaryl, and cycloalkyl. Substituents containing up to 19 carbon atoms, particularly hydrocarbon substituents, are preferred. The β- substituted-β-propiolactones are represented by the structural formula: wherein R is the non-interfering substituent. The β-substituted-β-propiolactone polyester produced by the present method has a repeat unit having the formula: wherein R is the non-interfering substituent.

The polyhydroxyalkanoate polymer obtained has a weight average molecular weight of at least about 100,000, preferably at least about 500,000, more preferably at least about 600,000, and even more preferably greater than about 600,000. In one embodiment the polyhydroxyalkanoate polymer has a weight average molecular weight of from about 600,000 to about 1 ,000,000. As used herein, the polydispersity index refers to the ratio of weight average molecular weight to number average molecular weight (M_w/M_n). The polymer has a polydispersity index of less than about 2, preferably from about 1 .1 to about 1 .6.

EXAMPLES

All initiator preparations disclosed herein are conducted in glassware which is flame dried while being flushed with an inert gas, such as argon or dry nitrogen, and finally is maintained under a positive pressure of an inert gas. Transfers of the initiator solutions are carried out either by cannulation or with a syringe, under an inert gas atmosphere. The polyhydric alcohol for the initiator preparation is typically dried over 3A molecular sieve. The organic zinc compound used to prepare the initiator is obtained as a solution in hydrocarbon solvent, such as toluene, and used in this solvent.

All β-substituted-β-propiolactone monomers are dried by several distillations from calcium hydride under vacuum prior to use. Enantiomerically enriched [S]-β-butyrolactone and [R]-β-butyrolactone is synthesized. The monomer is purified by fractional or spinning-band distillations under vacuum prior to the distillation from calcium hydride.

Racemic β-butyrolactone may be further purified by distillation several times from CaH₂ under reduced pressure with the final distillation onto neutral alumina (activity I) or activated 3A molecular sieve, which is flamed under vacuum prior to the distillation. The monomer is stored over this alumina or molecular sieve. Just prior to polymerization, either the neat monomer or a solution of the monomer is passed through an alumina column or a combined alumina/molecular sieve column under dry inert gas, such as dry argon, directly into the polymerization vessel. Enantiomerically enriched monomer (e.g., [R]-β-butyrolactone or [S]-β- butyrolactone) may be further purified by distillation from CaH₂. Optionally, it may be chromatographed on neutral alumina (activity I) with pentane as eluent. The fractions are analyzed by gas chromatography for purity and the middle cuts are combined and distilled from CaH₂ onto alumina, stored over alumina or molecular sieve, and passed through an alumina column a combined alumina/molecular sieve column as described above for the racemic monomer.

In each of the following examples the following basic procedure, unless otherwise noted, is used to prepare the polymer. The ampules or flasks to be used for the polymerization are septum capped, and flamed dried while flushing with argon. All reactants added to the ampules are transferred with a syringe or canula under an inert gas atmosphere.

An initiator composition is prepared by mixing a polyhydric alcohol, an organic zinc compound having two organic groups and solvent. The appropriate monomer and, optionally, solvent is transferred into an ampule or flask, and an amount of the initiator composition sufficient to give an initiating ratio of zinc atom to monomer is added. Polymerization reactions in the ampules are carried out at temperatures of from about 20°C to about 100°C for time periods ranging from about 3 hours to about 10 days, more preferably from about 17 hours to about 65 days, for homopolymerizations and copolymerizations. At the end of the polymerization reaction period the reaction may optionally be terminated with acetic acid or 2,4-pentanedione.

The crude products are clear, colorless viscous liquids or white solids depending on whether amorphous or semi-crystalline polymers are formed. Bulk reaction products are taken up into chloroform and recovered by precipitation into an ether-hexane (3:1 ) mixture or methanol. Solution reaction products are diluted with an amount of chloroform sufficient to reduce viscosity, and recovered by precipitation into an ether-hexane (3:1 ) mixture or methanol. The polymer is dried under vacuum at a temperature of from about room temperature (about 19°C) to about 50°C.

The molecular weights and melting temperature (Tm) of Examples are given. Melting temperatures are determined by differential scanning calorimetry (DSC). Molecular weight determinations are made by gel permeation chromatography (GPC) and molecular weights are reported in terms of the number average (Mn) and weight average (Mw) molecular weights. The

1 13 polydispersities or ratio of Mw to Mn are also reported. H and C NMR spectra are obtained for the various products to assist in the determination of the structures by measuring stereoregularity and tacticity effects of the polymers

1 produced. In the case of the copolymers, the H NMR spectra is useful in determining the copolymer compositions. Yields of the various products are also reported in the tables which follow after the Examples.

All molecular weight data reported in the Tables which follow are obtained by GPC using either three Phenogel or Ultrastyragel linear 5 μm columns (one 50 x 7.8 mm and two 300 x 7.8 mm) in series. A refractive index detector is used. Samples are prepared at 0.2% in CHCI₃, which is also the mobile phase (1.0 mL/min). Calibration is performed with narrow polystyrene standards and data is analyzed with Waters Expert Ease or Millenium software. NMR spectra were recorded on either a General Electric QE-300, a Varian Unityplus 300 or a Bruker AC-300 (at 300 MHz for H spectra) in deuteriochloroform. Chemical shifts are

13 reported in ppm from a TMS internal standard C NMR measurements are recorded at 75.4 Mhz. All spectra are recorded at 25°C-30°C, and CDC1₃ and

13 1 tetramethylsilane (TMS) are used as internal references for C and H NMR

3 spectra, respectively.

Melting temperatures (Tm) for polymer samples are determined with a Mettler T3000 system and the data processed with Mettler GraphWare TA72 software. The sample is heated at 10 °C/min. The melt temperature (Tm) is reported as the peak maximum, and the glass transition temperature (Tg) is reported as the transition mid-point.

The reaction temperature will preferably be in the range of 20°C to 100°C, more preferably from about 40°C to about 80°C, even more preferably from about 45°C to about 65°C. If a faster reaction time is desired, the temperature is preferably from about 70°C to about 80°C, more preferably about 75°C. The reaction time will typically range from about 5 to about 90, preferably from about 17 to about 65, hours for both homopolymerization and copolymerization reactions, however, the time may be as short as about 3 hours and as long as about 10 days or more.

Preparation of Initiator An initiator in accordance with the present invention is prepared by addition of dry, argon sparged 2,4-dimethyl-2,4-pentanediol (0.78 mL, 0.7197 g, 5.44 mmol) dropwise from a syringe to a dry, septum-capped, argon purged flask, containing 9.67 mL (8.8486 g) of 1.1 M (15 wt% ) diethylzinc in toluene (11.0 mmol diethylzinc). The evolved ethane is removed by venting through a needle attached to a bubbler with or without an argon purge. The reaction mixture may warm depending on the rate of addition. Occasionally, a small amount of solid will form. This solid can be dissolved by the addition of more dry toluene (1 mL) or gentle warming of the solution to 30-35°C. Also, the initiator can be used as is with stirring. The initiator is used in Examples 1-10, 11A and 12.

Example 1 (Solution Homopolymerization of Racemic β-Butyrolactone in Toluene)

Purified, dry racemic β-butyrolactone (23.9 g) and dry toluene (212.90 g) are transferred to a dry, argon purged, septum-capped flask via cannula. A portion of this solution is run down an alumina column into a septum-capped, argon purged flask (126.0 g solution, 12.4 g lactone, 144 mmol). Initiator solution (38.8 μL, 1.11 M in zinc, 0.03 mol% zinc to monomer) is added, and the reaction is heated at 65°C for 45 hours. Then, chloroform (150 mL) is added to flask to reduce the solution viscosity. The product, atactic poly(3-hydroxybutyrate) is recovered by precipitation into rapidly stirring ether-hexane mixture (3:1 v/v). The resulting gum is isolated by decanting the liquid after clarification, and it is dried under vacuum at 50 °C.

Example 2 (Bulk Homopolymerization of Racemic β-Butyrolactone)

Purified, dry racemic β-butyrolactone is run down an alumina column into a septum capped, argon purged flask (10.6 g, 123.0 mmol). Initiator solution (33 μL, 1.11 M in zinc, 0.03 mol% zinc to monomer) is added, and the reaction mixture is heated as in Example 1. Chloroform (250 mL) is added to dissolve the solid which is recovered as in Example 1.

Example 3 (Solution Homopolymerization of Racemic β-Butyrolactone in THF)

The basic procedure described in Example 1 is followed with 17.82 g (207 mmol) of racemic β-butyrolactone, 187 μL of initiator solution (0.1 mol% of monomer), and 136 mL of tetrahydrofuran (THF). Polymerization is carried out at 50°C for 67 h.

Example 4 (Solution Homopolymerization of Racemic β-Butyrolactone in Toluene)

The basic procedure described in Example 1 is followed (except that the monomer toluene solution is dried over 3A molecular sieves for at least 2 d instead of running down an alumina column) with 14.4 g (167 mmol) of racemic β-butyrolactone, 152 μL of initiator solution (0.1 mol% of monomer), and 101.3 mL of toluene. Polymerization is carried out at 100°C for 7 h.

Example 5 (Solution Homopolymerization of [R] β-Butyrolactone in Toluene)

Purified, dry [R]-β -butyrolactone (17.06 g) and dry toluene (148.6 g) are transferred to a dry, argon purged, septum-capped flask via cannula. This solution is run down an alumina column into a septum-capped, argon purged flask (155.0 g solution, 16.0 g lactone, 186 mmol). Initiator solution (50.1 μL, 1.11 M in zinc, 0.03 mol% zinc to monomer) is added, and the reaction is heated at 65°C for 65 hours. The reaction is terminated by adding glacial acetic acid (2 drops), and chloroform is added to reduce the solution viscosity. The product, isotactic poly(3-hydroxybutyrate) is recovered by precipitation into rapidly stirring ether-hexane mixture (3:1 v/v). The resulting white solid is isolated by filtration and is dried under vacuum at 50°C. Example 6 (Solution Copolymerization of [R] β-Butyrolactone and [R]-β-Propyl-β- propiolactone in Toluene)

Purified, dry [R]-β-butyrolactone (99.93 g), [R]-β-propyl-β-propiolactone (6.98 g) and dry toluene (803.7 g) are transferred to a dry, argon purged, septum-capped flask via cannula. This solution is run down an alumina column into a septum-capped, argon purged flask (753.8 g solution, 90.66 g lactones). Initiator solution (187 μL, 1.11 M in zinc, 0.02 mol% zinc to monomer) is added, and the reaction is heated at 60°C for 65 hours. Chloroform (3 L) is added to reduce the solution viscosity. The product, isotactic poly(3-hydroxybutyrate-co-3- hydroxyhexanoate) is recovered by precipitation into rapidly stirring ether-hexane mixture (3:1 v/v). The resulting white solid is isolated by filtration and is dried under vacuum at 40°C. The copolymer contains 6.2 mol% 3-hydroxyhexanoate

1 units as determined by H-NMR.

Example 7 (Solution Copolymerization of [R] β-Butyrolactone and [R]-β-Propyl-β- propiolactone in Toluene)

The basic procedure described in Example 6 is followed with 151.3 g lactone monomers (11 mol% [R]- β-propyl-β-propiolactone) and 661.6 g toluene after passing through the alumina column, and 288 μL of initiator solution (0.02 mol% of monomer). Polymerization is carried out at 65°C for 65 hours. The copolymer contains 10.8 mol% 3-hydroxyhexanoate units as determined by H- NMR.

Example 8 (Solution Copolymerization of [R] β-Butyrolactone and [R]- β-Pentyl- β-propiolactone in Toluene)

Purified, dry [R]- β-butyrolactone (1031.8 g) and [R]- β-pentyl- β- propiolactone (168.8 g) are combined in a dry, argon purged, septum-capped, 2 L flask via cannula transfer. This monomer mixture is divided between 3 additional dry, argon purged, septum-capped, 2 L flasks. Dry toluene (5310 g total) is divided among the flasks. These solutions are and run down a column packed with a plug of alumina (2 g) below 200 g of activated 3A molecular sieves and combined in a septum-capped, argon purged, 12 L flask (6773 g solution, 1175 g lactones). Initiator solution (2.3 mL, 1.11 M in zinc, 0.02 mol% zinc to monomer) is added, and the reaction is heated at 65°C for 70 hours. The reaction is terminated by addition of acetic acid (0.5 mL). The warm mixture is transferred to a 50 L flask and diluted with chloroform (28 L) to reduce the solution viscosity. The product, isotactic poly(3-hydroxybutyτate-co-3- hydroxyoctanoate) can be recovered by precipitation into rapidly stirring ether- hexane mixture (5:1 v/v) or methanol. The resulting white solid is isolated by filtration, and it is dried under vacuum initially at room temperature with an air sweep. The copolymer contains 8.4 mol% 3-hydroxyoctanoate units as

1 determined by H-NMR.

Example 9 (Solution Copolymerization of [R] β-Butyrolactone and [R]- β-

Pentadecyl-β-propiolactone in Toluene)

The basic procedure described in Example 6 is followed with 129.4 g lactone monomers (10 mol% [R]-β-pentadecyl-β-propiolactone) and 533.6 g toluene after passing through the alumina column, and 223 μL of initiator solution (0.02 mol% of monomer). Polymerization is carried out at 60°C for 88 hours. The copolymer contains 9.7 mol% 3-hydroxyoctadecanoate units as determined by

¹H-NMR.

Example 10 (Solution Copolymerization of [R] β-Butyrolactone and s- Caprolactone in Toluene)

The basic procedure described in Example 6 is followed with 107.1 g lactone monomers (12 mol% e-caprolactone) and 475.8 g toluene after passing through the alumina column, and 545 μL of initiator solution (0.02 mol% of monomer). Polymerization is carried out at 65 °C for 65 hours. The copolymer contains 11.5 mol% 6-hydroxyhexanoate units as determined by H-NMR. Example 11 (Comparison of inventive initiator and prior art initiator)

A. Purified, dry racemic β-butyrolactone (201.7 g) and dry toluene (1201 g) are transferred via cannula to a dry, argon purged, septum-capped flask. A portion of this solution is run down an alumina column into a septum- capped, argon purged flask (157.7 g solution, 22.6 g lactone, 263 mmol). Initiator solution (236 μL, 1.11 M in zinc, 0.1 mol% zinc to monomer) is added, and the reaction is heated at 65°C for 64 hours. The reaction is terminated with acetic acid (18 drops), and then chloroform is added to the flask to reduce the solution viscosity. The product, atactic poly(3-hydroxybutyrate) is recovered by precipitation into rapidly stirring cooled (with dry ice to -35°C) ether-hexane mixture (3:1 v/v). The resulting gum is isolated by decanting the liquid after clarification, and it is dried under vacuum at 40°C.

B. A portion of the same solution used in part A (150.1 g solution, 21.5 g lactone, 250 mmol) is run through the same procedure except that the polymerization is initiated with a prior art initiator comprising ethylzinc isopropoxide in toluene (225 μL, 1.11 M in zinc, 0.1 mol% zinc to monomer).

Example 12 (Bulk Homopolymerization of e-Caprolactone)

Purified, dry e-caprolactone is charged to a septum capped, argon purged flask (8.49 g, 74.4 mmol). Initiator solution (67 μl, 1.11 M in zinc, 0.1 mol% zinc to monomer) is added, and the reaction mixture is heated at 65°C for 24 hours. Chloroform (200 mL) is added to dissolved the solid which is recovered by precipitation into methanol (2 L). The product, polycaprolactone, is dried under vacuum at 40°C .

Table I. Polymerization Conditions

Example Temperature Time Zn/monomer Yield

(°C) ( ) (mol %) (%)

1 65 48 0.03 90.7

2 65 48 0.03 83.2

3 50 67 0.1 84.6 100 7 0.1 96.6

5 65 65 0.03 88.3

6 60 65 0.02 90.0

7 65 65 0.02 93.2

8 65 70 0.02 95.6

9 60 88 0.02 90.6

10 65 65 0.05 97.9

11A 65 64 0.1 96.7

11B 65 64 0.1 96.2

12 65 24 0.1 92.3

Table II. Product Characterization of Examples in Table I

Example Mn Mw Mw/Mn Tm (°C)

1 333,000 505,000 1.52 -

2 251,000 399,000 1.59 -

3 95,400 139,000 1.46 -

4 116,000 165,000 1.43 -

5 380,000 572,000 1.51 156

6 521,000 765,000 1.47 131

7 410,000 665,000 1.62 113

8 437,000 643,000 1.47 129

9 333,000 530,000 1.59 126

10 408,000 685,000 1.52 130

11A 163,000 271,000 1.66 -

11B 69,500 100,000 1.44 -

12 205,000 380,000 1.85 67

Mn = number average molecular weight Mw = weight average molecular weight Tm = melting point, temperature at which crystalline structure becomes liquid.

A dash (-) indicates that the polymer is atactic. Atactic polymers do not have crystalline structures, and therefore do not have a melting point. Additional embodiments and modifications within the scope of the claimed invention will be apparent to one of ordinary skill in the art. Accordingly, the scope of the present invention shall be considered in the terms of the following claims, and is understood not to be limited to the details of the methods described in the specification.

Claims

WHAT IS CLAIMED IS:

1. A composition produced by mixing a polyhydric alcohol, an organic zinc compound having two organic groups and a solvent, wherein the composition is substantially homogeneous, and wherein preferably the molar ratio of organic zinc compound to the number of hydroxyl groups on the polyhydric alcohol is from 0.5:1 to 2:1.

2. A composition according to claim 1 wherein the organic zinc compound has the structure:

RZnR wherein each R is independently a Cι-₈ alkyl group, phenyl, napthyl, a Cι-₃ alkyl- substituted phenyl, a Cι-₃ alkyl-substituted napthyl, a cycloalkyl group having from 4 to 6 ring carbon atoms, or dicyclopentadienyl; wherein the organic zinc compound is preferably selected from dimethylzinc, diethylzinc, dipropylzinc, dibutylzinc, dipentylzinc, dihexylzinc, diheptylzinc, dioctylzinc, di-2-ethylhexylzinc, diphenylzinc, ditolylzinc, dicyclobutylzinc, dicyclopentylzinc, di- methylcyclopentylzinc, dicyclohexylzinc, methyl phenylzinc, methyl tolylzinc, methyl naphthylzinc, ethyl phenylzinc, and mixtures thereof.

3. A composition according to claim 1 or 2 wherein the polyhydric alcohol is selected from 2,4-dimethyl-2,4-pentanediol, triethylene glycol and mixtures thereof.

4. A composition according to any of claims 1-3 wherein the solvent is selected from toluene, xylenes, tetrahydrofuran and mixtures thereof.

5. A method of forming a polymer characterized in that it comprises the steps of: a) mixing a polyhydric alcohol, an organic zinc compound having two organic groups and a solvent to form a homogenous initiator composition; b) mixing lactone monomer in the presence of the initiator composition to form a monomer mixture; and c) heating the monomer mixture to obtain the polymer.

6. A method according to claim 5 wherein the weight average molar ratio of the number of hydroxyl groups on the polyhydric alcohol to the organic zinc compound is 1 :1 and wherein the step of mixing lactone monomer in the presence of the initiator composition to form a monomer mixture preferably comprises mixing lactone monomer, initiator composition and an additional amount of a solvent.

7. A method according to claim 5 or 6 wherein the initiator composition is heated to a temperature of not greater than about 50°C, more preferably not greater than about 35°C, prior to the addition of the monomers.

8. A method according to any of claims 5-7 wherein the polymer has a weight average molecular weight of at least 100,000, more preferably from 600,000 to 1 ,000,000, and a polydispersity index of less than 2, more preferably from 1.1 to 1.6.

9. A method according to any of claims 5-8 wherein the lactone monomers are selected from β-alkyl-β-propiolactone, β-butyrolactone, e-caprolactone, δ- valerolactone and mixtures thereof.

10. A method according to any of claims 5-9 wherein the polyhydric alcohol is selected from 2,4-dimethyl-2,4-pentanediol, triethylene glycol and mixtures thereof.