WO2008009997A1

WO2008009997A1 - Polymerisation process

Info

Publication number: WO2008009997A1
Application number: PCT/GB2007/050430
Authority: WO
Inventors: Steven Melvin Howdle; Kristofer James Thurecht; Wenxin Wang; Andrew Mark Gregory
Original assignee: The University Of Nottingham
Priority date: 2006-07-21
Filing date: 2007-07-20
Publication date: 2008-01-24
Also published as: GB0614623D0

Abstract

The present invention relates to a process for preparing a polymer by dispersion polymerisations controlled by reversible addition fragmentation chain transfer (RAFT) agents. More specifically, the invention relates to a process for the production of well defined spherical polymer and copolymer beads, on the micrometer scale, of uniform size (monodisperse microspheres). The molecular architecture of the beads can be controlled to a great extent using the RAFT agent. The present invention also provides monodisperse microspheres having unique layered architecture.

Description

Polymerisation Process

This invention relates to a process for the production of well defined spherical polymer and copolymer beads, on the micrometer scale, of uniform size (monodisperse microspheres). In addition, the molecular architecture of the beads can be controlled to a great extent using a reversible addition fragmentation chain transfer (RAFT) agent. Additional features of the invention relate to the process of in-situ cleavage of the RAFT terminal end groups and purification of the polymer using supercritical fluids. Polymer microspheres have a range of applications including paints, toner, pigments, films, drug delivery devices, car tyres and cosmetics.

Polymers are chains of repeating units called monomers. The types of monomers used and how they link together can produce an enormous variety of different types of polymeric product. If more than one type of monomer is used the product is described as a co-polymer. The architecture of the final (co)polymer product is dependent on the types of monomers used, how these monomers are linked together and how long the chains are. If the chains are of varying lengths the (co)polymer is said to be polydisperse. Ideally, the (co)polymer chains should be of similar lengths, i.e. monodisperse, which yields a (co)polymer with uniform morphology and physical properties. The molecular weight and therefore chain length of a polymer can be controlled by judicious choice of an agent used to mediate the polymerisation, of which there are several. These agents can control the rate of the initiation, addition (propagation) and termination steps that ultimately determine the polydispersity of the (co)polymer produced.

Arguably the most important breakthrough in polymer science in recent years has been the use of controlled/living polymerisation techniques and agents to produce high quality and high performance polymers. Controlled/living polymerisations are superior to conventional polymerisation methodologies because they allow greater control of the rate of monomer addition to the growing polymer chain. Controlled/living polymerisations also ensure that the polymer chains grow at the same rate, producing chains that are of the same length (a polymer with low polydispersity). Control over the rate of monomer addition gives the polymer manufacturer the ability to produce polymers with well- defined molecular weights. In addition, this increased degree of control also allows the polymer producer to manipulate the architecture of the final polymer product. Living polymerisations controlled by RAFT (Reversible Addition Fragmentation chain Transfer) agents have particular advantages because they have the ability to form polymers and copolymers with very narrow molecular weight distributions from a wide range of monomers. Additionally, the resulting (co)polymers are free from metal impurities which are present in other controlled/living polymerisation methods such as Catalytic Chain Transfer Polymerisation and Atom Transfer Radical Polymerisation.

Dispersion polymerisation is a technique used to obtain monodisperse (co)polymer microspheres in the size range from 500 nm to 50 μm in diameter. A dispersion polymerisation is a method of polymerisation where the monomer is soluble in the media (usually a volatile organic based solvent) but the growing polymer chains become insoluble, once a certain molecular weight is achieved. To avoid the polymer precipitating out of solution (so-called precipitation polymerisation) the growing chains are separated and dispersed throughout the media by employing a dispersant or surfactant. If a surf actant/dispers ant was not employed the growing polymer chains would aggregate and fall out of solution, this would cause the viscosity of the polymer mixture to rise and control of the polymerisation would be lost resulting in a (co)polymer product with a high polydispersity. Another important effect of a surf actant/dispers ant is that they maintain a spherical environment in which the (co)polymer can grow. If a dispersion polymerisation is successful, the final (co)polymer particles are of a well-defined spherical shape. There are also additional advantages to conducting polymerisations in a dispersed media, these include: i) The viscosity of the media remains low, because the polymer is dispersed throughout the media. High viscosity is disastrous for polymerisation systems because control of the polymerisation is lost, resulting in high polydispersities and 'run-away' reactions, ii) The final (co)polymer product is particulate in nature and does not need further processing.

To date, the advantages of dispersion polymerisations and RAFT polymerisations have not been combined. The incompatibility of these techniques has been attributed to non-complimentary interactions between the polymer and stabilizer/surfactant leading to coagulation of the particles, or loss of control of the polymerisation due to poor diffusion of the controlling agent through the different phases of the system. The design of dispersants and stabilizers for dispersion polymerizations is an area of intensive research but to date no satisfactory solution to this problem has been found.

Furthermore there have not been any successful attempts to use ScCO₂ as a dispersing phase for controlled/living radical dispersion polymerisations. Previous attempts may have been unsuccessful because of poor diffusion of the controlling agents between the solvent and the polymer, though the exact reasons for the lack of success are unclear. These early attempts utilised a type of stabilizer with the controlling agent attached to the CO₂-phobic head group of the stabilizer. These "inistab" (initiator-stabiliser) dispersions yield relatively polydisperse and agglomerated products. There is also the additional disadvantage that these stabilizers are often difficult to synthesise and limit the application of the product.

Surprisingly, we have found that a near critical or supercritical fluid, for example carbon dioxide (scCO₂), can be used as a dispersing phase for conducting dispersion polymerisations. Using the process of the invention we have found that efficient polymerisations to be conducted provided that an appropriate stabiliser/surfactant is used.

The present disclosure relates to a process for preparing a polymer using a fluid in its supercritical or near critical state as a dispersing phase for conducting dispersion polymerizations in the presence of a stabilising agent which functions to ensure partition between the growing polymer chain and the fluid which contains unreacted monomer, the process comprising the steps of: i) adding an initiator, a RAFT agent and a stabilising agent to a sealable pressure vessel, ii) adding a first monomer to the pressure vessel, iii) sealing the vessel and introducing the fluid used as a dispersing phase, iv) raising the temperature and/or pressure of the vessel so that the fluid is in a near critical or supercritical state and maintaining this condition for a first period of time, v) optionally introducing a second monomer to the pressure vessel whilst maintaining the fluid in a near critical or supercritical state and maintaining this condition for a second period of time, and vi) returning the sealed vessel to ambient conditions of temperature and pressure to separate the reactant from the fluid.

According to a first aspect of the present invention there is provided a process for preparing a polymer using a fluid in its supercritical or near critical state as a dispersing phase for conducting dispersion polymerizations in the presence of a stabilising agent, the process comprising the steps of: i) adding a RAFT agent and optionally a stabilising agent to a sealable pressure vessel, and exposing the resulting mixture to an initiator, ii) adding a first monomer to the pressure vessel, iii) sealing the vessel and introducing the fluid used as a dispersing phase, iv) raising the temperature and/or pressure of the vessel so that the fluid is in a near critical or supercritical state and maintaining this condition for a first period of time, v) optionally introducing a second chain extending species to the pressure vessel whilst maintaining the fluid in a near critical or supercritical state and maintaining this condition for a second period of time, and vi) returning the sealed vessel contents to ambient conditions of temperature and pressure to separate the reactant from the fluid.

According to a second aspect of the present invention there is provided a process for preparing a polymer using a fluid in its supercritical or near critical state as a dispersing phase for conducting dispersion polymerizations in the presence of a stabilising agent, the process comprising the steps of: i) adding a RAFT agent and optionally a stabilising agent to a sealable pressure vessel, and exposing the resulting mixture to an initiator, ii) adding a first monomer and a second chain extending species to the pressure vessel, iii) sealing the vessel and introducing the fluid used as a dispersing phase, iv) raising the temperature and/or pressure of the vessel so that the fluid is in a near critical or supercritical state and maintaining this condition for a first period of time, v) optionally introducing a second initiator to the pressure vessel whilst maintaining the fluid in a near critical or supercritical state and maintaining this condition for a second period of time, and vi) returning the sealed vessel contents to ambient conditions of temperature and pressure to separate the reactant from the fluid.

According to a third aspect, the present invention provides a microsphere having a molecular weight dispersity of less than 1.5, preferably, less than 1.2.

The initiator may be any conventional initiator. In an embodiment, the initiator is a chemical compound (or compounds), heat or radiation. For example, the initiator may be UV light, gamma radiation, a thermal initiator or a redox initiator.

In an embodiment, the initiator is azobisisobutylonitrile (AIBN). In another embodiment, the initiator is azobis 4-cyanopentanoic acid (ACP). In another embodiment, the initiator is benzoyl peroxide.

The RAFT agent may be any conventional RAFT agent. The process of the present invention is intended specifically to include the use of all RAFT agents described in J. Polym. Sci. Part A: Polym. Chem.: Vol. 43 (2005), 5347-5393 or in WO98/01478. The reader is directed to the above reference for direction as to suitable RAFT agents which can be used in the process of the present invention and these RAFT agents are intended to form part of the present invention. In an embodiment, the RAFT agent is a RAFT agent disclosed in the above references. In an embodiment, the RAFT agent is a thiocarbonylthio compound e.g. a dithioester, dithiocarbamate, trithiocarbonate or xanthate.

In a further embodiment, the RAFT agent has the following formula:

R¹

wherein,

R¹ is hydrogen or is selected from the group comprising: aryl, (C₁-Cs)^yI, (C₁- C₈)alkoxy, (C₂-C₈)alkenyl, (C₂-C₈)alkynyl, (C₃-C₈)cycloalkyl, (C₁-C₈)alkylaryl carbamoyl, di-(Ci-C₈)alkyl-phosphonato, diaryl-phosphonato, (U-(C₁-Cs)^yI- phosphinato, diaryl-phosphinato and -SR⁵, wherein each of the aforementioned groups may be optionally substituted by 1 to 3 substituents, where chemically possible, independently selected from the group comprising: halo, (Q-GOalkyl, hydroxy, cyano, amino and nitro;

R² and R³ are each independently selected from the group comprising: hydrogen, (C₁- Ci₂)alkyl, (d-Ci₂)alkoxy, (C₂-Ci₂)alkenyl, (C₂-C ₁₂)alkynyl, (C₃-C₈)cycloalkyl, aryl, and (Ci-C₁₂)alkylaryl, wherein each of the aforementioned groups may be optionally substituted by 1 to 5 substituents, where chemically possible, independently selected from the group comprising: halo, (Q-GOalkyl, hydroxyl, cyano, amino, and nitro; R⁴ is selected from the group comprising: (Ci-C₁₂)alkyl, (C₃-C₈)cycloalkyl, aryl, COOH, COOZ, COOR and -CN, where Z is a suitable counter ion and R is (Q-C^alkyl; and R⁵ is hydrogen or is selected from the group comprising: (C₁-C₁₂)alkyl, (Q-C^alkoxy, (C₂-C₁₂)alkenyl, (C₂-C ₁₂)alkynyl, (C₃-C₈)cycloalkyl, aryl, (C₁-C₁₂)alkylaryl, wherein each of the aforementioned groups may be optionally substituted by 1 to 5 substituents, where chemically possible, independently selected from the group comprising: halo; (C₁- CzOalkyl; hydroxy; cyano; amino; and nitro.

In an embodiment, R¹ is selected from the group comprising: aryl, (Ci-C₈)alkyl, (C₁- C₈)alkoxy, (C₂-C₈)alkenyl, (C₂-C₈)alkynyl, (C₃-C₈)cycloalkyl and (C₁-C₈)alkylaryl, wherein each of the aforementioned groups may be optionally substituted by 1 to 3 substituents, where chemically possible, independently selected from the group comprising: halo, (Q-CzOalkyl, hydroxy, cyano, amino and nitro. Preferably, R¹ is aryl. More preferably, R¹ is phenyl or naphthyl. In an alternative embodiment, R¹ is -SR⁵.

In an embodiment, R² and R³ are each independently selected from the group comprising: hydrogen, (Ci-C₈)alkyl, (CrC₈)alkoxy, (C₂-C₈)alkenyl, (C₂-C₈)alkynyl, (C₃- C₈)cycloalkyl, aryl, and (Ci-C₈)alkylaryl, wherein each of the aforementioned groups may be optionally substituted by 1 to 3 substituents, where chemically possible, independently selected from the group comprising: halo, (Q-CzOalkyl, hydroxyl, cyano, amino, and nitro.

Preferably, R² is hydrogen, optionally substituted (Ci-C₈)alkyl, (Ci-C₈)alkoxy or optionally substituted aryl. More preferably, R² is hydrogen, optionally substituted (C₁- CzOalkyl, (Q-CzOalkoxy or optionally substituted aryl. Preferably, R is hydrogen, optionally substituted (C₁-C₈)^yI, (Q-CsMkoxy or optionally substituted aryl. More preferably, R³ is hydrogen, optionally substituted (C₁- C₄)alkyl, (Q-CzOalkoxy or optionally substituted aryl.

In an embodiment, R⁴ is -CN. In an alternative embodiment, R⁴ is selected from the group comprising: (Q-Q^alkyl, (C₃-Cs)cycloalkyl, aryl, COOH and COOR, where R is (Ci-C₆)alkyl. Preferably, R⁴ is aryl or COOH.

In an embodiment, R is optionally substituted (C₁-C₁₂)alkyl or optionally substituted (Ci-Ci₂)alkoxy.

Suitable counter ions include Group IA or Group HA metals with Na and K being preferred.

In an embodiment the RAFT agent is α-cyanobenzyl dithionaphthylate.

In a preferred embodiment, the RAFT agent has the following formula:

In another preferred embodiment, the RAFT agent has the following formula:

In another preferred embodiment, the RAFT agent has the following formula:

In another preferred embodiment, the RAFT agent has the following formula:

In a preferred embodiment, the RAFT agent has the following formula:

In another preferred embodiment, the RAFT agent has the following formula:

The stabiliser may be any conventional stabiliser capable of ensuring partition of monomer and polymer. The process of the present invention is intended to include the use of all stabilisers described in J. Eastoe et al., Current Opinion in Colloid and Interface Science, 8, (2003), 267-273. The reader is directed to the above reference for direction as to suitable stabilisers which can be used in the process of the present invention and these stabilisers are intended to form part of the present invention. In an embodiment, the stabiliser a species capable of stabilising a free radical polymerisation in CO₂. In an embodiment the stabiliser is polydimethylsiloxane monomethacrylate (PDMS-MMA). In an embodiment, the stabiliser is Krytox TM, which has the following formula:

In the context of the present invention, the terms 'stabiliser', 'stabilising agent' and 'surfactant' are used interchangeably and refer to a substance that functions to ensure partition between the growing polymer and the fluid solution containing monomer. The surfactant functions to keep the growing polymer separate from the monomer solution. It is this partitioning of monomer and polymer which enables the polymer to keep growing in the dispersion in the form of spherical particles. The presence of the stabiliser/surfactant is thus important to the efficient functioning of the process. Any conventional polymerisation stabiliser can be used in the process of the present invention. In an alternative embodiment, one compound can function as both the RAFT agent and the stabiliser (a macroRAFT agent). In other words, the RAFT agent and stabiliser can be part of the same molecule. The process of the present invention is intended to include the use of all combined RAFT agents and stabilisers described in Z. Ma, P. Lacroix- Desmazes, Polymer, 45, 6790, (2004), 6789-6797. The reader is directed to the above reference for direction as to suitable combined RAFT agents and stabilisers which can be used in the process of the present invention and these combined RAFT agents and stabilisers are intended to form part of the present invention. When using a macroRAFT agent, the concentration of the stabiliser can be high and can be up to 50% with respect to the monomer.

In an embodiment the vessel is an autoclave.

In an embodiment, the sealed vessel contents are returned to ambient conditions of temperature and pressure by slow venting or spray collection.

In an embodiment, the dispersion polymerisation is a controlled dispersion polymerisation. In other words, the dispersion polymerisation may be controlled to provided polymers of desired polymer chain length and/or low molecular weight dispersity.

In an embodiment, the initiatoπRAFT ratio is in the range between 1:20 and 5:1 inclusive. In another embodiment the initiator: RAFT ratio is in the range between 1:5 and 2:1 inclusive. In another embodiment, the initiatoπRAFT ratio is in the range between 1:4 and 2:1 inclusive. In another embodiment, the initiatoπRAFT ratio is in the range between 1:2 and 2:1 inclusive. In another embodiment, it is in the range between 1:1 and 1:2 inclusive.

In another embodiment, the monomeπRAFT ratio is in the range between 20000:1 and 10:1. Preferably the ratio is in the range between 5000:1 and 100:1. Preferably the ratio is in the range between 2000:1 and 100:1. Preferably the ratio is in the range 2000:1 and 600:1. Preferably, the ratio is 2000:1. Preferably, the ratio is 600:1.

In another embodiment, the stabiliser is present in an amount of between 1 and 50 wt% with respect to the monomer. Preferably, the stabiliser is present in an amount between 2.5 and 10 wt% with respect to the monomer.

In one embodiment of the various aspects of the present invention, the chain extending species is a second monomer. The first and second monomer may be the same or different. Many conventional monomers may be used in the process of the present invention. Specific monomers that find application include: acrylamide, acrylate, acrylic acid, acrylonitrile, 1,3 -butadiene, cyanoacrylate, ethyl acrylate, ethylene, ethylene oxide, methacrylic acid, methyl methacrylate, propylene, styrene, vinyl acetate, vinyl chloride and vinylsilane. Particularly preferred monomers are acrylic acid, acrylates, styrenics and derivatives thereof. Other preferred monomers include vinyl monomers used in conventional free-radical polymerisation. In an embodiment, the first and second monomer are each independently acrylate monomers. Preferable monomers include methyl methacrylate (MMA), tertiary-butyl acrylate (tBA), methacrylic acid (MA) and styrene.

Monomers can be added alone or optionally in combination with a suitable solvent.

In some embodiments, the fluid used as a dispersing phase is in the supercritical or near critical state.

A supercritical fluid (SCF) is defined as a substance which is above the critical pressure and critical temperature for that substance, but below the pressure required to form a solid. The term "supercritical" is used herein to denote a fluid which is above its critical temperature and pressure. The term "near critical" refers to a fluid which is under conditions of temperature and pressure below its critical point but the conditions of temperature and pressure are such that the density of the fluid is sufficient to ensure that the monomer but not the polymer being formed are substantially in a single phase with said fluid.

The reaction will operate in the fluid at temperatures and pressures below the critical point of the fluid being used as the solvent, provided that the density of the, fluid is sufficient to ensure that the monomer is present in the fluid in substantially in a single phase. These conditions are hereafter referred to as being near-critical. Usually, however, the conditions employed will be supercritical i.e. the fluid is at temperature and pressure above its critical point. Preferably the conditions of temperature and pressure are above the critical point of the solvent.

Particularly favoured media to have in the reaction system as component in a supercritical condition include carbon dioxide, sulphur dioxide, nitrogen, alkanes such as ethane, propane and butane, alkenes, ammonia, and halocarbons (CFCs and HFC's) such as trichlorofluoromethane, dichlorofluoromethane, dichlorodifluoromethane, chlorotrifluoromethane, bromotrifluoromethane, trifluoromethane, and hexafluoroethane. The choice of supercritical fluid is only limited by the engineering constraints but particularly favoured fluids are carbon dioxide and nitrogen, and nitrogen is of particular interest. Other fluids such as halocarbons or hydrocarbons or a mixture of fluids could also be used.

The fluid may be a mixture of two or more fluids having critical points which do not require commercially unacceptable conditions of temperature and pressure in order to achieve the necessary conditions for reaction according to the present invention. For example, mixtures of carbon dioxide with an alkane such as ethane or propane, or a mixture of carbon dioxide and sulphur dioxide may be employed close to or above their theoretical critical points.

Preferred fluids have a good solvating power and are not incompatible with the polymerisation process. Carbon dioxide is particularly preferred on account of its the unique properties. Often SCFs, and particularly ScCO₂, are described of having properties intermediate of those of a liquid and a gas, i.e. they can behave like solvents and dispersing phases while at the same time being diffuse in nature like a gas.

One of the advantages of using a ScCO₂ as a solvent in the process of the present invention is that it enables facile product separation. By simply depressurizing the reaction vessel the ScCO₂ solvent/dispersant simply evaporates and leaves no solvent residue on the product. This is a particular advantage over other polymerisation methods which require further purification by removing the solvent and/or any unreacted monomer.

When combined with the right stabilizer/surfactant, ScCO₂ has proven to be an excellent dispersing phase for conducting dispersion polymerizations. Stabilisers/surfactants suitable for the process of the invention generally have a CO₂-philic head group and a hydrocarbon chain. Preferred stabilisers/surfactants are fluorinated hydrocarbons or siloxanes. Many stabilisers/surfactants useful in the invention are commercially available.

In another embodiment the first period of time is from 1 to 72 hours. Preferably, the first period of time is from 4 to 72 hours. Preferably, the first period of time is from 4 to 48 hours. In a separate embodiment the second period of time is from 1 to 72 hours. Preferably, the second period of time is from 4 to 72 hours. Preferably, the second period of time is from 4 to 48 hours.

Contrary to expectations, the present invention demonstrates that RAFT mediated dispersion polymerizations can be conducted in ScCO₂, to yield monodisperse polymer micro-particles with extremely low molecular weight dispersity. This has been done using simple commercially available stabilizers. In addition to this, the polymer exhibits true 'living' character, with the polymer strands growing upon the addition of more monomer and initiator after the original polymerisation has been purified (chain extension). If the polymerisation was not living the addition of monomer and initiator to the purified polymer would yield new polymer chains, rather than the chain extension of the original polymer. This living character results in a polymer which maintains low polydispersity.

The living character of these controlled/living dispersion polymerizations has been further utilised; many types of monomers, and combinations of monomers, can be polymerized to produce a wide variety of polymer and copolymer monodisperse microspheres. It has been demonstrated that polymer beads exhibiting miscible micro- morphology between the components is possible during the dispersion (i.e. beads with a single phase comprised of different polymers). There are no known examples in the prior art of monodisperse (co)polymer particles being produced by RAFT dispersion polymerisation. Monodisperse microspheres with unique layered architecture have also been produced. These monodisperse core-shell particles consist of a core of one type of polymer and an outer layer of another. It is also possible to increase the number of layers as desired. The advantages of the method of the present invention to produce core-shell particles are several fold: i) The method is a true dispersion technique to yield particles in a specific size range, ii) Improved control over the composition and thickness of the layers of the spheres can be achieved. iii) The process is not limited by monomer choice. iv) Core-shell particles are formed by block copolymerisation rather than blending two distinct polymers together, which enhances stability and versatility.

Conventional RAFT mediated dispersion polymerisations usually yield coloured products, due to the RAFT terminal groups remaining on the polymer. The colours depend on the RAFT agent used. In addition to the benefits described, the present invention overcomes this limitation by facilitating the cleavage of the RAFT terminal end groups from the polymer and purification in-situ to yield colourless polymer particles.

The invention is illustrated by the following Figures in which: FIGURE 1 shows a Scanning Electron Micrograph of particles produced by RAFT mediated dispersion polymerisation conducted in ScCO₂. The perfectly spherical particles are clearly evident, and

FIGURE 2 shows a Transmission Electron Micrograph of the core shell particles. The microtome process has slightly distorted the particles into an oval shape. The shell of the particles can be clearly seen.

FIGURE 3 shows the molecular weight of polymer vs. conversion with various RAFT agents ♦ (1); -*■ (2); ^ (3); X (4). Theoretical molecular weight based on RAFT agent concentration is shown in the solid line and theoretical molecular weight based on RAFT agent and AIBN concentrations is shown in the dashed line.

FIGURE 4 shows a Scanning Electron Microscopy Image of PMMA particles formed using PDMS-RAFT.

Preferred embodiments of the invention will now be illustrated by way of the following examples.

Example 1 - Typical Procedure

RAFT dispersion for homopolymer 10 mg AIBN, 40 mg RAFT (α-cyanobenzyl dithionaphthylate) and 150 uL stabiliser

(PDMS-MA) was added to 20 rnL reactor and flushed with nitrogen gas for 10 minutes.

3 rnL of degassed MMA was then added to the autoclave under nitrogen.

The autoclave was sealed, heated to 65 ⁰C and pressurised to 4000 psi with stirring for 40 hours.

AIBN:RAFT molar ratio - 1:2

Conversion: 99% Appearance: fine, peachy coloured powder

Mn: 34000 Da, Mw: 40000 Da PDI: 1.17

Morphology: Spherical particles in size range 1-5 microns

Example 2 - Copolymer formation

10 mg AIBN, 40 mg RAFT (α-cyanobenzyl dithionaphthylate) and 150 uL stabiliser

(PDMS-MA) was added to 20 mL reactor and flushed with nitrogen gas for 10 minutes.

3 mL of degassed MMA was then added to the autoclave under nitrogen.

Following the initial polymerisation period, 10 mg AIBN and 2 mL styrene were added to the cell via a high-pressure inlet port. The polymerisation was allowed to proceed for a further 40 hours.

Mn: 42kDa Mw: 50.IkDa PDI: 1.19 Dry, free-flowing pink powder recovered with spherical particulates in the size range 1-5 microns. TEM shows core-shell morphology. NMR results show a styrene concentration of 30 mol%.

Example 3 - Reaction time: varied for monomer conversion.

* Entry one is no raft agent added - note the very high polydispersity.

* Entries 2-5 are for Initiator: RAFT ratios of 1:1 and show good PDIs (less than 1.3).

* Entry 6 is for InitiatoπRAFT ratio of 1:2 - this shows lower conversion but much better control.

* Entry 7 proves that this is a living polymerisation by chain extension of the original polymer. Here the original polymer (entry 3) was purified then put it back into the reaction vessel with more monomer and initiator. Proof of living polymerisation is shown by the increase in molecular weight of the original chain, rather than just another polymer growing. Hence, there must be RAFT groups on the end of the original polymer and the new monomer just adds on there, rather than initiating new polymer chains.

* The particles are between 1-5 microns by SEM (FIGURE 1). Example 4 - Copolymer and Core- Shell Formation

The polymerisation is performed in a one-pot, two step process. Initially, 3 mL of MMA, 5 wt % stabiliser, AIBN, RAFT α-cyanobenzyldithiobenzoate and CO₂ is added to a 20 mL autoclave. Reaction proceeds for 2 days at 65 ⁰C and 4000 psi.

2 mL of styrene + AIBN is then added to the reaction vessel via a high-pressure inlet tap. This reaction is allowed to proceed for another 2 days.

Final polymer has PDI < 1.5 and particulate morphology in range of 1-5 microns. TEM (FIGURE 2) shows that micro-morphology can be core-shell or phase separated species depending on the conditions of the experiment.

Example 5 - Kinetic control from different RAFT agents (M_n vs M_nth) for PMMA

This example illustrates the results obtained for the PMMA polymers obtained using RAFT agents (1, 2, 3 and 4) for different reaction times in ScCO₂ according to the process of the present invention.

M_n is the molecular weight, M_ntn is the theoretical molecular weight and PDI is the polydispersity.

Example 6 - linear molecular weight progression with conversion.

This example provides evidence for living polymerisation. As can be seen in figure 3, the molecular weight of polymer increases linearly with % conversion for various RAFT agents: #^• (1), -^ (2), ^ (3), and X (4). Theoretical molecular weight based on RAFT agent concentration is shown in the solid line and theoretical molecular weight based on RAFT agent and AIBN concentrations is shown in the dashed line.

Example 7 - Targeted molecular weight in ScCO₂ using various concentrations of RAFT agent 3. (Methodology is applicable for a range of molecular weights).

This example illustrates the results obtained for reactions performed with MMA (1.56 M), RAFT agent 3 (1.25 x 10^"2 M, 3.12 x 10^"3 M, 7.80 x 10^"4 M for theoretical molecular weights of 12500, 50000 and 200000 g mo iP-l at 100 % MMA conversion based on the RAFT agent respectively) and 5 wt% PDMS (with respect to the monomer) in 60 mL autoclave at 65 ⁰C and 4000 psi, unless otherwise stated. b) The % conversion was calculated from ¹H NMR. c) The molecular weight was calculated using a refractive index detector in THF (calibrated with poly(styrene) standards). d) The theoretical molecular weight is based on RAFT agent concentration.

Dp is the degree of polymerisation (how many monomer units are incorporated into the polymer chain). Example 8 - Targeting lower weight polymers for MALDI-TOF analysis using RAFT agents 3 and 4 (functionalised end-groups - various ratios of [RAFT]: [initiator]).

a) Reactions performed with MMA (1.56 M), RAFT (1.56 x 10^~2 M), initiator (3.90 x 10^~3 M) for theoretical molecular weight of 10000 at 100 % MMA conversion based on the RAFT agent respectively and 5 wt% PDMS-MA (with respect to the monomer) in 60 mL autoclave at 65 ⁰C and 4000 psi, unless otherwise stated; b) from ¹H NMR; c) calibrated with poly(styrene) standards in THF using a refractive index detector; d) theoretical molecular weight based on RAFT agent concentration.

Example 9 - Effect of Stabiliser concentration using RAFT agent 3.

a) Reactions performed with MMA (1.56 M), RAFT (6.24 x 10^"3 M), AIBN (6.24 x 10^"3

M) for theoretical molecular weight of 25000 g mo il-^"l at 100 % MMA conversion based on the RAFT agent respectively and 0.00, 2.50, 5.00 and 10.0 wt% PDMS-MA (with respect to the monomer) in 60 mL autoclave at 65 ⁰C and 4000 psi, unless otherwise stated; b) from ¹H NMR; c) calibrated with poly(styrene) standards in THF using a refractive index detector; d) theoretical molecular weight based on RAFT agent concentration.

Example 10 - Changing RAFT concentrations and applying to different monomers.

Example 11 - Polymerisation using macroRAFT agents - combined stabiliser and RAFT agent on the one molecule.

In these experiments, the stabiliser and RAFT agent are part of the same molecule, called a macroRAFT agent. These results show that the macroRAFT method works in ScCO₂.

VAc-RAFT (Mn - 2.3 or 7.6 kDa)

PFOMA-RAFT (Mn - 15 kDa)

[M]: [CTA]: [I] is the ratio of monomer to RAFT agent to initiator concentrations. M_th is the theoretical molecular weight based on initiating species. In all cases, azobisisobutyronitrile (AIBN) was used as the initiator.

Claims

1. A process for preparing a polymer using a fluid in its supercritical or near critical state as a dispersing phase for conducting dispersion polymerizations in the presence of a stabilising agent, the process comprising the steps of: i) adding a RAFT agent and optionally a stabilising agent to a sealable pressure vessel, and exposing the resulting mixture to an initiator, ii) adding a first monomer to the pressure vessel, iii) sealing the vessel and introducing the fluid used as a dispersing phase, iv) raising the temperature and/or pressure of the vessel so that the fluid is in a near critical or supercritical state and maintaining this condition for a first period of time, v) optionally introducing a second chain extending species to the pressure vessel whilst maintaining the fluid in a near critical or supercritical state and maintaining this condition for a second period of time, and vi) returning the sealed vessel contents to ambient conditions of temperature and pressure to separate the reactant from the fluid.

2. A process for preparing a polymer using a fluid in its supercritical or near critical state as a dispersing phase for conducting dispersion polymerizations in the presence of a stabilising agent, the process comprising the steps of: i) adding a RAFT agent and optionally a stabilising agent to a sealable pressure vessel, and exposing the resulting mixture to an initiator, ii) adding a first monomer and a second chain extending species to the pressure vessel, iii) sealing the vessel and introducing the fluid used as a dispersing phase, iv) raising the temperature and/or pressure of the vessel so that the fluid is in a near critical or supercritical state and maintaining this condition for a first period of time, v) optionally introducing a second initiator to the pressure vessel whilst maintaining the fluid in a near critical or supercritical state and maintaining this condition for a second period of time, and vi) returning the sealed vessel contents to ambient conditions of temperature and pressure to separate the reactant from the fluid.

3. The process as claimed in claim 1 or claim 2, wherein the initiator is a chemical compound or compounds, heat or radiation.

4. The process as claimed in claim 3, wherein the initiator is azobisisobutylonitrile (AIBN), azobis 4-cyanopentanoic acid (ACP) or benzoyl peroxide.

5. The process as claimed in any preceding claim, wherein the RAFT agent has the following formula:

wherein, R¹ is hydrogen or is selected from the group comprising: aryl, (C₁-Cs)^yI, (C₁- C₈)alkoxy, (C₂-C₈)alkenyl, (C₂-C₈)alkynyl, (C₃-C₈)cycloalkyl, (C₁-C₈)alkylaryl carbamoyl, di-(Ci-C₈)alkyl-phosphonato, diaryl-phosphonato, (U-(C₁-Cs)^yI- phosphinato, diaryl-phosphinato and -SR⁵, wherein each of the aforementioned groups may be optionally substituted by 1 to 3 substituents, where chemically possible, independently selected from the group comprising: halo, (Q-GOalkyl, hydroxy, cyano, amino and nitro;

R² and R³ are each independently selected from the group comprising: hydrogen, (C₁- C₁₂)alkyl, (C₁-C₁₂)alkoxy, (C₂-C₁₂)alkenyl, (C₂-C ₁₂)alkynyl, (C₃-C₈)cycloalkyl, aryl, and (Ci-C₁₂)alkylaryl, wherein each of the aforementioned groups may be optionally substituted by 1 to 5 substituents, where chemically possible, independently selected from the group comprising: halo, (Q-GOalkyl, hydroxyl, cyano, amino, and nitro; R⁴ is selected from the group comprising: (Ci-C₁₂)alkyl, (C₃-Cs)cycloalkyl, aryl, COOH, COOZ, COOR and -CN, where Z is a suitable counter ion and R is (Q-QOalkyl; and R⁵ is hydrogen or selected from the group comprising: (Ci-C₁₂)alkyl, (Ci-C₁₂)alkoxy, (C₂-C₁₂)alkenyl, (C₂-C ₁₂)alkynyl, (C₃-C₈)cycloalkyl, aryl, (Ci-C₁₂)alkylaryl, wherein each of the aforementioned groups may be optionally substituted by 1 to 5 substituents, where chemically possible, independently selected from the group comprising: halo; (C₁- C₄)alkyl; hydroxy; cyano; amino; and nitro.

6. The process as claimed in claim 5, wherein R¹ is aryl, R² and R³ are each independently selected from the group comprising: hydrogen, optionally substituted (C₁- Cs)alkyl, (Q-CsMkoxy and optionally substituted aryl and R⁴ is -CN.

7. The process as claimed in claim 5, wherein R¹ is -SR⁵, R² and R³ are each independently selected from the group comprising: hydrogen, optionally substituted (C₁- C₄)alkyl, (Ci-C₄)alkoxy and optionally substituted aryl, R⁴ is aryl or COOH and R⁵ is optionally substituted (Q-Q^alkyl or optionally substituted (C₁-C₁₂)alkoxy.

8. The process as claimed in any preceding claim, wherein the stabiliser a species capable of stabilising a free radical polymerisation in CO₂, preferably the stabiliser is polydimethylsiloxane monomethacrylate (PDMS-MMA) or Krytox.

9. The process as claimed in any preceding claim, wherein the initiatoπRAFT ratio is in the range between 1:20 and 5:1 inclusive, preferably the ratio is in the range between 1:5 to 2:1 inclusive.

10. The process as claimed in any preceding claim, wherein the monomeπRAFT ratio is in the range between 20000:1 to 10:1, preferably the ratio is in the range between 2000:1 and 100:1.

11. The process as claimed in any preceding claim, wherein the stabiliser is present in an amount between 1 - 50 wt% with respect to the monomer, preferably the stabiliser is present in an amount between 2.5 - 10 wt% with respect to the monomer.

12. The process as claimed in any preceding claim, wherein the chain extending species is a second monomer.

13. The process as claimed in any preceding claim, wherein the monomers are vinyl monomers used in conventional free-radical polymerisation.

14. The process as claimed in any preceding claim, wherein the fluid is carbon dioxide.

15. The process as claimed in any preceding claim, wherein the temperature and pressure are above the critical point of the fluid.

16. The process as claimed in any preceding claim, wherein the first period of time is from 1 to 72 hours.

17. The process as claimed in any preceding claim, wherein the second period of time is from 1 to 72 hours.

18. The process as claimed in any preceding claim, wherein the RAFT agent and stabiliser are a single molecule.

19. A microsphere having a molecular weight dispersity of less than 1.5, preferably, less than 1.2.