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Title:
POLYPHTHALATE PLASTICIZERS THAT DO NOT RELEASE ENDOCRINE DISRUPTING COMPOUNDS
Kind Code:
A1
Abstract:
Novel polyphthalate compounds that do not release phthalate esters under environmental conditions, and methods for making the same.


Application Number:
US2013/024582
Publication Date:
08/08/2013
Filing Date:
02/04/2013
Assignee:
THE REGENTS OF THE UNIVERSITY OF CALIFORNIA (Office Of Technology Transfer, 1111 Franklin Street,5th Floo, Oakland CA, 94607, US)
International Classes:
C08F18/18; C08F12/08; C08F12/22; C08F112/14; C08F118/18; C08F212/14; C08F218/18; C08L27/06; C08L31/08
View Patent Images:
Attorney, Agent or Firm:
BELL, Adam, W. (Bell & Associates, 58 West Portal Avenue # 121San Francisco, CA, 94127, US)
Claims:
CLAIMS

1. A compound comprising a polyphthalate polymer with a covalent carbon chain backbone having pendant phthalate esters that under environmental conditions do not release phthalate esters, and wherein hydrolysis of the polymer releases only alcohol residues, and does not release phthalate residues.

2. The compound of claim 1 wherein the environmental conditions are as follows: 10 weeks immersed in water at neutral pH at 37 °C.

3. The compound of claim 2 further comprising a plastic where said plastic is in need of

plasticization.

4. The compound of claim 3 where said plastic is poly vinyl chloride (PVC).

5. The compound of claim 2 wherein the polyphthalate polymer is a polyvinylphthalate ester polymer.

6. The compound of claim 5 wherein the polyphthalate polymer is a polyvinylphthalate ester homopolymer.

7. The compound of claim 5 wherein the polyphthalate polymer is a polyvinylphthalate ester copolymer.

8. The compound of claim 7 wherein the polyvinylphthalate ester copolymer is a random copolymer.

9. The compound of claim 7 wherein the polyvinylphthalate ester copolymer is a block copolymers.

10. The compound of claim 2 wherein the polyphthalate polymer is a copolymer with a comonomer selected from the group consisting of: styrene, substituted styrene derivatives, acrylates, methacrylates, acrylamides, methacrylamides, acrylonitrile, dienes and maleimides.

11. The compound of claim 8 wherein the random copolymer is poly-(vinylphthalate-co-acrylate).

12. The compound of claim 2 comprising a polymer having a molecular weight of between 2000 and 25000, and a Degree of Polymerization (DP) between 9 and 130.

13. The compound of claim 2 wherein the spacing between pendant phthalate esters is between zero monomers and 200 monomers.

14. A compound of claim 3 wherein no covalent bonds are formed between the plastic and polyphthalate polymer.

15. The composition of claim 14 wherein the plastic is PVC.

16. The compound of claim 5 consisting of a substantially pure a polyvinylphthalate ester polymer with a covalent carbon chain backbone having pendant phthalate esters.

17. The composition of claim 16 that under environmental conditions (10 weeks immersed in water at neutral pH at 37 °C) does not release phthalate esters, and wherein hydrolysis of the polymer releases only alcohol residues, and does not release phthalate residues.

18. A method for plasticization of a compound, the method comprising: (a) polymerization of polyphthalate ester monomers to produce a plasticizing polymer with a covalent carbon chain backbone and phthalate ester side-groups wherein hydrolysis of the plasticizing polymer releases only alcohols and does not release phthalates, (b) providing plastic in need a plasticization, (c) mixing the plasticizing polymer and the plastic.

19. The method of claim 18 wherein the polyphthalate ester monomers are polyvinylphthalate ester monomers.

20. The method of claim 19 wherein polyvinylphthalate ester monomers are 4-vinylphthalate ester monomers.

21. The method of claim 18 wherein the plastic is poly vinyl chloride (PVC).

22. The method of claim 18 wherein the plasticizing polymer is a homopolymer of polyvinylphthalate esters.

23. The method of claim 18 wherein the plasticizing polymer is a random copolymer of

polyvinylphthalate esters.

24. The method of claim 18 wherein the plasticizing polymer is a poly-(vinylphthalate-co-acrylate).

25. The method of claim 18 wherein the method comprises polymerizing 4-vinylphthalate ester monomers in a controlled manner using Nitroxide Mediated Radical Polymerization (NMRP) wherein polymerization is carried out at a temperature between 120°C and 126°C using unimolecular alkoxyamine initiators, neat in the monomer without the presence of a solvent to produce short polymers of a covalent carbon chain backbone bearing phthalate ester side-groups.

Description:
UNITED STATES PATENT AND TRADEMARK OFFICE

INTERNATIONAL PATENT APPLICATION

Title: Polyphthalate plasticizers that do not release endocrine disrupting compounds

Inventor: Dr. Rebecca Braslau (Santa Cruz, CA) Address for inventor:

Department of Chemistry, UCSC, 1156 High Street, Santa Cruz, CA 95064, USA Assignee:

The Regents of the University of California

Office of Technology Transfer

1111 Franklin Street, 5th floor

Oakland, California 94607 USA

Attorneys for the applicant

BELL & ASSOCIATES

58 West Portal Avenue # 121

San Francisco, California 94127

info@bell-iplaw.com

PTO Customer No. 039843

[001] Statement of support

This invention was made with support of the following: None. [002] Relationship to other applications

The present international application claims priority to and the benefit of the following US provisional patent application(s), all of which are hereby incorporated by reference: US

Application No. 61/594,052, filed 02 February 2012, titled Polyphthalate plasticizers that do not release endocrine disrupting compounds. [003] Field of the invention

The field of the invention encompasses plasticizers, in particular, alternative polyphthalate compounds comprising well-defined short polymers containing pendant phthalate esters that under common environmental conditions do not release phthalate esters into the environment, which are known to be endocrine disruptors. The field of the invention also encompasses methods for making and using such compounds and plastics (such as PVC) blended with such compounds.

[004] Background

Phthalates (also called phthalate esters) are esters of phthalic acid (1,2-benzenedicarboxylic acid) and are mainly used as plasticizers (added to plastics to increase their flexibility, transparency, durability, and longevity). They are primarily used to soften polyvinyl chloride. Shown below is a generic chemical structure of a phthalate. R and R' = CnH2n+1; n = 4-15.

[005] Since the 1930's small molecule phthalate esters have been used very commonly (approx. 6 million tons per year) for the formulation of PVC consumer products. Phthalates are relativly easily leached from the plastic matrix into the environment due to the fact that there is no covalent bond between the phthalates and plastics in which they are mixed. As plastics age and break down, the rate of release of phthalates accelerates. In use, phthalate esters leach from the polymer matrix, and when metabolized, can give rise to molecules that, to certain endocrine receptors, structurally and functionally resemble hormones, and therefore act as endocrine disruptors. These endocrine disruptors are implicated in a variety of serious health problems including male and female reproductive tract abnormalities, and feminization, miscarriage, menstrual problems, changes in hormone levels, early puberty, brain and behavior problems, impaired immune functions, developmental abnormalities, infertility and cancer. These dangers have been recognized and phthalate plasticizers have been banned from a number of specific applications including child care products and some toys. The use of the specific phthalate esters DEHP, DBP (dibutyl phthalate) and BBP (butylbenzyl phthalate) in toys and other child care articles was forbidden by the European Union in 2005, and was banned by the Consumer Safety Commission in 2009 in the United States for toys marketed to children younger than 12 years old, and child care articles for children up to age 3. But phthalate plasticizers continue to be used for food packaging, medical devices and some toys, and also in articles such as rain coats and cosmetics. Phthalate plasticizers are also used in many other products such as automobile interiors, PVC pipes for drinking water. Such uses are causing increasing medical concern as data accumulates and awareness grows.

[006] A number of references are believed by the inventors to be particularly relevant to the present work and include the following: Rectanus, et al, 4-Vinylphthalic Anhydride - A New Monomer For Reactive Homopolymers And Copolymers. Polymer Bulletin 1994, 32, (4), 373-380. Gottschalk et al, Copolymers of 4-vinylphthalic acid derivatives in polymer blends. (BASF A.-G., Germany). Ger. Offen. (1993). Patent DE 4316024. Gottschalk et al, Polymer blends containing 4- vinylphthalic acid derivative copolymers. (BASF A.-G., Germany). Ger. Offen. (1995), 6 pp.

Patent DE 4338124. These publications are hereby incorporated by reference for all purposes. The fact that these references are cited is not an admission that they are prior art.

[007] The successful outcome of this project will have a huge beneficial impact on human health on this planet. It is recognized that children are particularly sensitive to the effects of leached phthalate plasticizers: certainly humans of all ages are exposed to large quantities of these hormone disruptors in modern society. These small molecule plasticizers leach out into the environment, disrupting the metabolism of wildlife, and generations of future humans. By developing a polymer- supported version of phthalate plasticizers, these materials are expected to be resistant to leaching. In addition, due to the robust all-carbon polymer backbone, any

polyphthlates that might be ingested cannot be metabolized into hormone mimics. This could revolutionize the plastics industry: most immediately providing solutions for children's products, food packaging, and medical applications.

[008] Brief description of the invention

The invention encompasses polyphthalate compounds comprising polymers containing pendant phthalate esters that under common environmental conditions do not release phthalate esters (which are known to be endocrine disruptors) in any significant amount. The invention also encompasses methods for making such compounds. The methods of making the compounds of the invention may use any suitable type of polymerization reaction, many of which are known in the art. For example, Nitroxide Mediated Radical Polymerization (NMRP) may be used. Other controlled and uncontrolled polymerization reactions may be used with one or more type of monomer reactant. The invention also encompasses compositions comprising a plastic in need of plasticization (such as PVC) blended with such compounds, and articles made with such compositions.

[009] In an exemplary embodiment, polymers containing pendant phthalate esters are prepared by Nitroxide Mediated Radical Polymerization (NMRP). The products may be used as plasticizers when blended with polyvinyl chloride (PVC) and other plastics.

[0010] In another exemplary embodiment of this new process, 4-vinylphthalate ester monomers are polymerized in a controlled manner by NMRP to give short polymers consisting of a covalent carbon chain backbone bearing phthalate ester side-groups. Hydrolysis of these designed polymers will release only alcohols, rather than phthalates. Thus degradation products cannot be metabolized to give hormone mimics that may cause endocrine disruption. Both homo- and co-polymers are prepared by the method of the invention, allowing the preparation of polymers with variable molecular weights, variable spacing between phthalate moieties, and variable polarity.

[0011] In one disclosed exemplary embodiment, the applicants used a 4-vinylphthalate ester, however, the invention equally encompasses use of vinylphthalate esters with different

substitutions, for example, 3, 4, 5 or 6 vinylphthalate esters (positions 1 and 2 already being occupied by the ester groups). All such variations are encompassed in the invention and all such variations should provide the same functional benefits.

[0012] The invention encompasses (but is not limited to) the following embodiments:

[0013] A polyphthalate polymer compound comprising low molecular weight (2000 - 25000) short (Degree of Polymerization = 9-130) polystyrene or polyacrylate or polyacrylamide polymers bearing pendant phthalate esters, that under experimental conditions described below release no detectable amount (less than 1% or alternatively less than 3%) of phthalate esters. These experimental conditions are as follows: Hydrolysis of PVC/polyphthalate films are performed by aging the films for 10 weeks at 37 °C, and alternatively at 70 °C in water at neutral and low pH following the procedure described in: Wang, Q.; Storm, B. K., Migration of additives from poly(vinyl chloride) (PVC) tubes into aqueous media. Macromolecular Symposia 2005, 225, 191- 203. [0014] ASTM methods are used to probe plasticizer extractability in organic solvents: ASTM D1239 - 07 extraction into hexanes at 50°C with mechanical stirring, and ASTM D2222 - 09 extraction into methanol with mechanical stirring (ASTM D1239 - 07 ("Standard Test Method for Resistance of Plastic Films to Extraction by Chemicals". In ASTM International, West

Conshohocken, PA: 2007; and ASTM D2222 - 09 "Standard Test Method for Methanol Extract of Vinyl Chloride Resins" in ASTM International, West Conshohocken, PA: 2009). Under these conditions, less than 50% (alternatively less than 30%, or less than 10%, or less than 5%, or less than 3%, or less than 1%) of the plasticizer is extracted (50% of DEHP is extracted from PVC under these conditions: Choi, J.; Kwak, S. Y., Hyperbranched poly(epsilon-caprolactone) as a nonmigrating alternative plasticizer for phthalates in flexible PVC. Environmental Science & Technology 2007, 41, (10), 3763-3768).

[0015] A polyphthalate compound comprising polymers containing pendant phthalate esters that under experimental conditions release no detectable amount (less than 1% or alternatively less than 3%) of phthalate esters. An assay used to measure the release of phthalate esters by hydrolysis of PVC/polyphthalate films may be performed by aging the films for 10 weeks at 37 °C (alternatively at 50°C, 60°C or 70°C) in water at neutral (and alternatively low) pH following the procedure described by Wang (see above).

[0016] A method for altering the physical properties of PVC by mixing the PVC with a plasticizer, wherein the plasticizer is a polyphthalate polymer compound comprising low molecular weight (2000 - 25000) polymers having pendant phthalate esters that under experimental conditions do not release phthalate esters. In alternative embodiments, the molecular weight of the polymers may be, for example, 500 to 2500000, or 1000 to 2000000, or 1500 to 1000000, or 2000 to 500000. Mixing may be done, for example, by solution casting (Lindstrom, et al., Journal of Applied Polymer Science 2006, 100, (3), 2180-2188) or may be done by any other suitable method of mixing such as simple mechanical mixing at a temperature that encourages blending of components. No covalent bonds are formed between the PVC and plasticizer. The plasticizer is a polyphthalate polymer compound comprising a preferably low molecular weight (2000 - 25000) polymer (Degree of Polymerization = 9-130), for example a polystyrene or polyacrylate or polyacrylamide polymer (or mixtures thereof) bearing pendant phthalate esters, that under standard experimental conditions (described herein) release no measurable phthalate esters (or in other embodiments, release <1 , or <3 , or <10 , or <20 , or <30 phthalate esters over a fixed and defined time, such as 10 weeks).

[0017] A method for preparing a polyphthalate compound, the compound comprising low molecular weight (2000 - 25000) short (Degree of Polymerization = 9-130) polystyrene or polyacrylate or polyacrylamide polymers bearing pendant phthalate esters, that under experimental conditions described herein release no detectable amount (less than 1% or alternatively less than 3%) of phthalate esters; the method comprising polymerizing 4-vinylphthalate ester monomers in a controlled manner using Nitroxide Mediated Radical Polymerization (NMRP) wherein

polymerization is carried out at a temperature between, for example 120°C and 126°C using unimolecular alkoxyamine initiators. Alternatively a higher or lower temperature range may be used, for example, temperatures may be 110°C to 140°C or 40°C to 200°C or 60°C to 175°C or 80°C to 155°C or 100°C to 150°C orl00°C to 135°C or 110°C and 130°C. The polymerization can be carried out neat (without a solvent) in the monomer without the presence of a solvent to produce short polymers of a covalent carbon backbone bearing phthalate ester side-groups.

Alternatively a solvent may be used for the polymerization reaction. Alternatively polymerization may be done by any other known method.

[0018] Brief description of the figures: See figures integrated into specification [0019] General Representations Concerning the Disclosure

The embodiments disclosed in this specification are exemplary and do not limit the invention. Other embodiments can be utilized and changes can be made. As used in this specification, the singular forms "a", "an", and "the" include plural reference unless the context clearly dictates otherwise. Thus, for example, a reference to "a part" includes a plurality of such parts, and so forth. The term "comprises" and grammatical equivalents thereof are used in this specification to mean that, in addition to the features specifically identified, other features are optionally present. Where reference is made in this specification to a method comprising two or more defined steps, the defined steps can be carried out in any order or simultaneously (except where the context excludes that possibility), and the method can optionally include one or more other steps which are carried out before any of the defined steps, between two of the defined steps, or after all the defined steps (except where the context excludes that possibility). Where reference is made herein to "first" and "second" features, this is generally done for identification purposes; unless the context requires otherwise, the first and second features can be the same or different, and reference to a first feature does not mean that a second feature is necessarily present (though it may be present). Where reference is made herein to "a" or "an" feature, this includes the possibility that there are two or more such features. This specification incorporates by reference all documents referred to herein and all documents filed concurrently with this specification or filed previously in connection with this application, including but not limited to such documents which are open to public inspection with this specification.

[0020] Definitions

The following words are used herein as follows:

- The word Plasticizer is used herein to describe any substance added to a polymer to chance plasticity, viscosity, fluidity, hardness or another physical quality of the polymer.

- The word Plastic refers to any polymeric organic amorphous solid compound that is moldable when heated and includes, for example PVC, acrylics, polyesters, silicones, polyurethanes, and halogenated plastics.

- When referring to 'short polymers' the applicant may mean a polymer with a DP (degree of polymerization) of between 2 and several thousand, for example 40 and 1000 or 10 and 100.

- The word Hormone is used herein to describe any compound that interacts with the endocrine system of an animal.

- The term Endocrine disruptor is used herein to describe any compound that interferes with the normal physiological functioning of the endocrine system of an animal.

- To say that a plasticizer does not release phthalate esters, in this disclosure, means that it does not release an appreciable amount of phthalate esters, or alternatively that it releases less than the amount of phthalate esters that a commonly used traditional plasticizer will release over the same period of time under the same conditions; for example no more than 10% or 20%. In other embodiments it may release no more than 30%, 40%, 50%, 60%, 70% or no more than 80% of phthalate esters that a commonly used traditional plasticizer will release over the same period of time. One defined method of measuring release is the Wang (above) method of aging a film for 10 weeks at 37°C in water at neutral pH (e.g. 7 to 7.4). For example a plasticizer made of short polymers consisting of a covalent carbon chain backbone bearing phthalate ester side-groups may release less than 30% (or alternatively less than 20%, 10%, 5%, 3%, 1% or less than 0.5%) of the phthalate esters that would be released, over the same period under the same conditions, by a plasticizer not made of short polymers consisting of a covalent carbon chain backbone bearing phthalate ester side-groups.

[0021] Detailed description of the invention

[0022] 1. Objectives

[0023] Phthalate Plasticizers

[0024] The most common and efficient plasticizers used for PVC (polyvinylchloride) products are branched alkyl phthalate esters of low molecular weight such as di-2-ethylhexyl phthalate (DEHP) 1 and diisononyl phthalate (DINP) 2 (Figure 1). The plasticizing effect is based on an increase of the free volume per volume of material, which results in a decrease of the glass transition temperature. While pure PVC is inherently a rigid and brittle material, the macroscopic effect of the addition of plasticizers is increased flexibility and workability, a reduced melt viscosity and lower elastic modulus. In 2005, phthalates made up 87% of the 10.4 billion pound/year (5.2 million ton/year) world-wide plasticizer market.

[0025] Because phthalates are not covalently bonded to PVC, they leach out of the polymer matrix into the environment. Humans are exposed to phthalates from a wide range of products such as food packaging, medical devices and toys. Studies on the migration of low molecular plasticizers and their decomposition products into food and biological fluids like saliva or blood and the resulting health risk have raised serious health concerns. Animal studies have shown that some phthalates, such as DEHP and their metabolic products, behave as Endocrine Disrupting

Chemicals (EDC). Although the exact influence of plasticizers and their metabolism products on human health is not completely understood, toxicological data indicates that phthalates may lead to a variety of medical problems, including endocrine disruption resulting in decreased sperm count, developmental abnormalities, and breast cancer. The use of the phthalate esters DEHP, DBP (dibutyl phthalate) and BBP (butylbenzyl phthalate) in toys and other child care articles was forbidden by the European Union in 2005, and was banned by the Consumer Safety Commission in 2009 in the United States for toys marketed to children younger than 12 years old, and child care articles for children up to age 3. The use of three additional phthalate esters: DINP, DIDP (diisodecyl phthalate) and DnOP (di-«-octyl phthalate) in toys and childcare products are now strongly restricted. Plasticizers are widely used in medical devices, food packaging, cosmetics and personal care products, furnishings, garden hoses, construction materials, toys, athletic shoes, and car interiors. Thus there is an ongoing need for effective "general purpose" plasticizers that cannot leach out of consumer products, yet still provide the desired plasticizing properties.

[0026] Polyester Plasticizers

Polymeric plasticizers demonstrate decreased migratory aptitude in comparison to small molecule phthalate plasticizers. Polyesters, such as poly(s-caprolactone) (PCL) 3 and poly(butylene adipate) (PBA) 4 (Figure 2), have been investigated as polymeric plasticizers since 1947. In 1977 Hubbel reported that poly(s-caprolactone) is compatible with PVC in a concentration range of 10% - 90%, and demonstrates efficient plasticizing properties. The plasticizing behavior of commercial elastomers such as polycaprolactone glycol-based thermoplastic urethanes (PCL/TPU Estane 54351 and PE/TPU Estane 58213 developed by Goodrich),

poly(ethylene- co-vinyl acetate-co-carbon monoxide) terpolymers (Elvaloy 741 and Elvaloy 742 developed by DuPont) and poly(l,3-butylene adipate) (REOPLEX® developed by Ciba-Geigy) have been investigated. These polymers are miscible with PVC, and display reduced migration in comparison to low molecular plasticizers, while their plasticizing effects are useful for specific applications. The influence of molecular weight and branching of poly(butylene adipate) s on the plasticizer efficiency and migration aptitude was recently studied by Hakkarainen. The major disadvantages of these polyesters is that the polymer backbone is susceptible to hydrolysis, which changes their physical properties with aging and exposure to moisture.

[0027]

Figure ,

Biodegradable polyester plasttcizers PCL and

PCL po}y( cspr !scionej PSA. po!yf utyierse aitipatej

[0028] Terpolymers prepared by uncontrolled, AIBN-initiated radical polymerization with various ratios of maleic anhydride, styrene and vinyl acetate (and derivatives obtained by opening the anhydride with alcohols) have been investigated as polymeric plasticizers. The plasticizing results were not optimal: blending with additional additives has been investigated. A terpolymer made of ethylene, vinyl acetate and carbon monoxide EVACO has been developed for food products. A diblock copolymer made of PEG and polycaprolactone has been developed for manufacturing flexible biomedical supplies.

[0029] The efficacy of polyesters as plasticizers is influenced by: Molecular weight: Polymeric plasticizers are characterized as low, medium or high molecular weight plasticizers, with average molecular weights ranging from 1,000 to 10,000. While the migration resistance improves with increasing molecular weight, the processability decreases. Miscibility: Molecular dynamics simulations by Lee of polyester blends with PVC indicate that a ratio of 3-4 methylene units per ester is a lower limit for miscibility, while the upper limit is 10-12 methylene units per ester, with an optimal ratio of 6 methylene units per ester, which is corroborated by experimental data: the melting point depression method gave an optimal ratio of 7, whereas thermodynamic

measurements gave an optimal ratio of 5, corresponding to PVC/poly(caprolactone) blends.

Branching: Slightly branched polymers enhance the plasticizing effect in terms of greater elongation and improved miscibility. Due to the higher density of chain ends in branched polymers, the free volume and mobility is higher in comparison to linear polymers with the same molecular weight. However high degrees of branching result in low miscibility and poor mechanical properties. Concentration: A concentration of approximately 40 wt % of polyester plasticizer is needed to obtain materials with elastomeric behavior. Endgroups: The polyester endgroups play a role in moderating the susceptibility of the polymeric plasticizer to hydrolysis. This effects the subsequent migration of monomeric degradation products from the PVC matrix. The inherent degradability of polyesters, leading to lower molecular weight hydrolysis products, makes these plasticizers of limited usefulness. Thus a robust, non-hydrolysable polymeric plasticizer with a non-hydrolizable backbone is desirable.

[0030] 2. Preparation of Poly(phthalate) plasticizers

The present invention entails preparation of poly(vinylphthalate ester)s, as homopolymers, or random copolymers with styrene, acrylates or other comonomers, to be used as substitutes for standard phthalate plasticizers in PVC. As phthalate esters are now used on the million ton scale annually, a substitute is desirable that is chemically similar, but which shows low migratory ability from the PVC matrix. As opposed to the current polyester plasticizers, these poly(vinylphthalates) are linked together by a robust carbon polymer backbone: hydrolysis will release only alcohols, rather than phthalates. Thus degradation products pose no danger of being metabolized to form Endocrine Disruptor Compounds.

[0031] Any appropriate method of polymerization may be used, and many are known in the art and commercial kits are available. In the present exemplary case, Nitroxide-mediated radical polymerization (NMRP) was used to prepare short homopolymers or copolymers with low polydispersities and predictable molecular weights. The inventors developed a number of nitroxides as mediators in this process. For vinylphthalate homopolymers the simple TEMPO- based alkoxyamine initiator based on TEMPO 12 (both available commercially from Sigma Aldrich Co.) is effective at producing well-defined polymers. For poly(vinylphthalate-co-acrylate)s, the alkoxyamine based on the alpha-hydrogen bearing nitroxide TIPNO (T-butyl-isopropyl- phenyl-nitroxide), which was developed in the inventor's (Dr. Braslau' s) lab, was used to form controlled polymers of predictable composition. Alternatively, and preferably for commercial applications, the very similar initiator BLOCKBUILDER® initiator based on the alpha-hydrogen bearing nitroxide SGI (13) is available commercially on large scale from Arkema Inc.

[0032] Figure below shows Nitroxides and their corresponding N-alkoxyamine initiators for preparing polymeric phthalates

[0033] NMP is an attractive method for this application. The polymerizations are typically carried out by heating in the range of 120-126 °C (other temperature ranges are possible - see above) using unimolecular alkoxyamine initiators, neat in the monomer (alternatively a solvent may be used). The radical nature of the polymerization makes this a chemoselective technique that is tolerant to a variety of functional groups on the monomers including esters, anhydrides, amides, alcohols, amines, epoxides, nitriles, and carbamates. The "Living" nature of the radical polymerization gives polymers of predicable molecular weights (e.g., PDI from about 1.2 to 1.8), and as no solvent is employed, the polymerizations are economical and scaleable to prepare bulk commodities at the industrial level. In some embodiments, solvent may be employed (but generally is not). Solvent may be added to ensure solubility of all of the components. In some embodiments super critical C02 may be used as the solvent.

[0034] A. Monomer synthesis

Although the following method was employed in the current work, it is well known in the art that there are many effective ways to couple the vinyl group onto the aryl bromide (or aryl iodide or aryl tosylate, etc). For the purpose of this investigation, the synthesis of 4-vinylphthalic esters is initially carried out by the most convenient manner possible, without regard to possible palladium catalyst impurities or economic concerns about scale-up. Once effective poly(phthalic ester) plasticizers are developed, routes that are economical and do not entail the use of potentially toxic catalysts become a priority.

[0035] The only literature method for the preparation of 4-vinylphthalic acid 15 is that of Stadler, utilizing a Heck reaction in an autoclave with 40 bars of ethylene gas. This group made

copolymers of 4-vinylphthalic acid, 4-vinylphthalic anhydride, and 4-vinylphthalic esters with styrene using uncontrolled AIBN-initiated radical polymerization, with the aim of making heat resistant polystyrenes and polymer blends with enhanced impact strength.

[0036] of d

[0050] The inventors have alternatively used a different synthesis method as described in the following reference, hereby incorporated by reference: JR. Braslau, et al "Polymeric phthalates: potential non-migratory macromolecular plasticizers," Journal of Polymer Science Part A: Polymer Chemistry, 2013, 51, 1775-1184. (March 1, 2013): doi: 10.1002/pola.26485.

[0051] As the 4-vinylphthalates are expected to be prone to polymerization upon handling and storage, it is prudent to prepare esters from the acid prior to introducing the vinyl group. Rather than carry out a Heck reaction it is known in the art that other methods may be used to couple the vinyl group onto the aryl bromide (or aryl iodide or aryl tosylate, etc).

[0052] A number of vinyl boron agents have been used to carry out this transformation on aryl bromides, including protocols by Molander and Najera with potassium vinyltrifluoroborate. Joucla has developed a heterogeneous palladium catalyst to be used with potassium vinyltriflouroborates. Alternatively, the use of vinyl boronic acids have been used by a number of research groups.

Burke has developed air- stable MID A boronates to replace unstable vinyl boronic acids in this Suzuki-Miyaura coupling.

Synthesis of 4- vinylphthalic esters 17 via Suzuki- Miyaura coupling

[0053] A much older approach entails preparation of an alkynyl phthalate ester 19 via a

Sonogashira coupling, followed by alkyne deprotection upon treatment with base with loss of acetone to give alkynylphthalic esters 20. The chemo selective reduction of the triple bond to the vinyl group should be straightforward.

Denmark's Pd cat. vinylsilane Denmark has developed the use of very inexpensive and coupling with aryl bromides stable vinylpolysiloxane 18 with tetra-butylammonium fluoride as an activator in a related palladium catalyzed coupling. This vinyl silane/TBAF system employs 5% PdBr2, 5% 2-(di-ieributylphosphino) biphenyl ligand. Electron poor aryl bromides react quickly compared to electron rich substrates, making this a very attractive method. Yamakawa has also developed a nickel catalyzed coupling of aryl bromides with vinyl

ZnBr MgBrCl.

Figure below shows Sonogashira route to vinyl phthalates

[0054] A less exotic approach is the Diels-Alder reaction between acetylene dicarboxylate esters

21 and the diene 22 developed by Tsuge. Esterification of acetylene dicarboxylic acid to the diester

22 is carried out by standard acid catalyzed Fischer esterification conditions. Treatment of the Diels-Alder product with DBU resulted in elimination reactions to give a mixture of the desired product 25 as the minor component, and the benzyl ether 24 as the major product. It should be possible to convert this mixture to the desired vinyl phthalate ester by treatment with acid.

Figure below shows Diels-Alder approach to 4-vinylphthalates based on the work of Tsuge.

H02C

[0055] Use of 4-vinylphthalic anhydride 26 as a monomer will allow post-polymerization modification of the polymer, but will result in incomplete esterification, leaving behind some carboxylic acid residues. However, incorporation of some phthalic anhydride into the polymer may prove to be a useful functional handle in allowing incorporation of other functional groups (such as imide formation) subsequent to polymerization. The group of Stadler prepared

4-vinylphthalic anhydride 26 from 4-vinylphthalic acid 15 by sublimation. In an analogous fashion, 4-bromophthalic acid should be easily converted in to the corresponding anhydride, followed by vinylation. This will allow for easier handling of the intermediates, without concerns of premature polymerization during storage.

Routes to

4-vinylphthalic

anhydride 26

Various alcohols may be used to prepare the Alcohols in phthalate plasticizers

vinylphthalate esters. The most common

plasticizer is DEHP, thus 2-ethylhexyl

alcohol is an obvious first choice. The

alcohols shown in Table 1 is investigated.

The differences in branching, molecular

weight, and polarity are all expected to affect

the free volume created in the PVC polymer,

thus contributing to the efficacy of the

polymeric plasticizers.

[0056] B. Polymerization by Nitroxide-Mediated Radical Polymerization (NMRP)

With the 4-vinylphthalate ester monomers in hand, polymerizations to form homopolymers and copolymers is carried out using NMRP. The resulting polymers is initially characterized by 1H- NMR of the crude polymerization mixture to determine the ratio of consumed to residual monomer, and then GPC to determine molecular weight and polydispersity.

[0057] i. Homopolymers

Short homopolymers using 4-vinylphthalate esters are prepared, varying the molecular weights between 2,000 - 25,000 (DP ~ 4 - 24), or in other embodiments between, for example 10 and 40. The miscibility properties of these materials with PVC are unknown. For those that are miscible, they are tested for efficacy as plasticizers, as indicated by the glass transition temperature and tensile strength of the resulting blends. A variety of 4-vinylphthalate monomers is investigated, by varying the alcohols making up the phthalate esters, and varying the molecular weight of these homopolymers. The TEMPO-based initiator is used for these polymerizations, as it is less costly than the H nitroxide-based initiators. It is understood that TEMPO, TIPNO, or many other nitroxide-based initiators can be used.

Figure below shows Homopolymerization of 4-vinylphthalate esters by NMRP

poly(vinylphthalate) homopolymers

[0058] ii. Random Co-polymers

The bulky phthalic ester moieties may cause the homopolymers to be too rigid to exhibit satisfying plasticizing properties. Thus random copolymers prepared by a mixture of 4-vinylphthalate esters and styrenes or acrylates are prepared. Styrene as a co-monomer will statistically spread apart the bulky phthalate sidegroups, but the parent polymer backbone is essentially polystyrene.

[0059] Alternatively, the use of acrylates will form copolymers that have polarity properties more closely related to the polyester plasticizers used today, without the susceptibility to backbone hydrolysis. It is possible that the acrylate "spacers" will act to isolate the bulky phthalate groups, allowing these copolymers to mimic traditional phthalate plasticizers when blended with PVC. As a rough guide in making the first selection of acrylates to be used, the optimal ratio determined by Lee of 5-7 methylene to ester units in polyesters to achieve maximal miscibility with PVC indicates that rc-butyl acrylate is a good initial choice. A slightly branched alcohol such as isobutyl alcohol is another good choice. Again, a polymer with molecular weights of 2000 - 10000 (DP ~ 4 - 24) is synthesized from 4-vinylphthalic esters and acrylates by NMRP. For these

polymerizations using acrylates, our alpha-H nitroxide-based initiator is used, with a small amount of alpha-H nitroxide added to the polymerization mixture to ensure a controlled, living process. Note that copolymers with acrylates having a DP of 16-48 were generally used in the present study, but in practice the DP value could be from 2 to several thousand.

Figure shows Random copolymerization of 4-vinylphthalate esters and acrylates by NMRP

[0060] An alternative embodiment encompasses the use of 4-vinylphthalic anhydride as a co- monomer, to provide for the opportunity of post polymerization modification.

Figure shows Random copolymerization of 4-vinylphthalate anhydride by NMRP:

post-polymerization modification of the anhydride residues

[0061] Variables: Variables include: alcohol on phthalate ester; molecular weight of polymer; identity and ratio of comonomer (for acrylates, alcohol of acrylate is another variable); ratio of polyphthalate plasticizer blended with PVC.

[0062] Solution cast films of PVC mixed with our designed phthalic ester polymers are prepared as described by Hakkarainen. These polymer blends are analyzed for miscibility and plasticizing effect, as well as stability.

[0063] Miscibility: Miscibility between the PVC and the polymeric phthalate plasticizers is determined by IR- spectroscopy and differential scanning calorimetry (DSC). Interactions between the CH2-C1- groups of PVC and the carbonyl groups of the polyesters are indicated by a shift of the carbonyl peak to lower wavenumbers. The existence of a single glass transition temperature is proof of full miscibility. Tensile Strength: The mechanical properties of PVC/poly(4- vinylphthalic ester) films is investigated by tensile strength analysis, a good method to determine elastomeric behavior. These new polymer blends is compared with PVC containing traditional phthalate plasticizers. Glass Transition Temperature: The plasticizing properties of the new polymer blends is probed by measuring the glass transition temperature, a good starting property is a Tg below -30 °C. Stability and migration of polymeric plasticizers: Hydrolysis of PVC/poly(4- vinylphthalic ester) films is performed by aging the films for 10 weeks at 37 °C in water. The degradation products is analyzed by GC-MS. Mass loss and water absorption of the films will also be measured.