MX338317B

Improved control over controlled radical polymerization processes.

Abstract

A procedure for improved temperature control in controlled radical polymerization processes is disclosed. The procedure is directed at controlling the concentration of the persistent radical in ATRP and NMP polymerizations procedures and the concentration of radicals in a RAFT polymerization process by feeding a reducing agent or radical precursor continuously or intermittently to the reaction medium through one of more ports.

MX338317B, drawing sheet 1 — Sheet 1 of 192

Term

No projected expiry on record.

20 claims: 5 independent, 15 dependent

1
CLAIMS REIVINDICACIONES 1. Un método para operar un proceso de polimerización ICAR ATRP, que comprende:(a) mezclar un monómero insaturado, un iniciador de polimerización radicálica de transferencia de átomos, un catalizador metálico y opcionalmente un ligando, para formar una mezcla;(b) añadir una cantidad inicial de agente reductor no activado a la mezcla;(c) adicionar una cantidad adicional de agente reductor no activado para regenerar el catalizador metálico en la mezcla a un velocidad proporcional con la velocidad de reacciones de terminación radical-radical;y (d) mantener el proceso de polimerización a o por arriba de una temperatura en donde el agente reductor no activado tiene un valor ti/2 dependiente de la activación de entre 30 segundos y 30 minutos. one. A method of operating an ICAR ATRP polymerization process, comprising: (a) mixing an unsaturated monomer, a radical atom transfer radical polymerization initiator, a metal catalyst and optionally a ligand, to form a mixture;(b) adding an initial amount of unactivated reducing agent to the mixture;(c) adding an additional amount of unactivated reducing agent to regenerate the metal catalyst in the mixture at a rate proportional to the rate of radical-radical termination reactions;and (d) maintaining the polymerization process at or above a temperature where the non-activated reducing agent has a value ti /2 dependent on activation between 30 seconds and 30 minutes.
16
The method according to claim 16. El método de conformidad con la reivindicación 15, en donde el proceso de polimerización se calienta a una primera temperatura antes de añadir la cantidad inicial del agente reductor no activado. 15, wherein the polymerization process is heated to a first temperature before adding the initial amount of the unactivated reducing agent.
17
The method according to claim 17. El método de conformidad con la reivindicación 16, en donde el proceso de polimerización se calienta a una segunda temperatura después de añadir la cantidad inicial del agente reductor no activado. 16, wherein the polymerization process is heated to a second temperature after adding the initial amount of the unactivated reducing agent.
18
The method according to claim 18. El método de conformidad con la reivindicación 17, en donde la segunda temperatura es por lo menos 10 grados más caliente que dicha primera temperatura. 17, where the second temperature is at least 10 degrees warmer than said first temperature.
19
The method according to claim 19. El método de conformidad con la reivindicación 15, en donde el agente reductor no activado se dispersa continuamente dentro de la mezcla caliente. 15, wherein the unactivated reducing agent is continuously dispersed within the hot mixture.

Independent claims5

800 paragraphs in 73 sections, as filed

(54) Title: IMPROVED CONTROL OVER RADICAL POLYMERIZATION CONTROLLED PROCESSES. (54) Title: IMPROVED CONTROL OVER CONTROLLED RADICAL POLYMERIZATION PROCESSES.

(57) Summary

A procedure is described for improving temperature control in controlled radical polymerization processes. The procedure is aimed at regulating the concentration of the persistent radical in ATRP (radical transfer atom polymerization) and NMP (nitroxide mediated polymerization) polymerization procedures and the concentration of radicals in a RAFT (chain transfer polymerization) polymerization process. (reversible addition / fragmentation) by continuously or intermittently feeding a reducing agent or radical precursor to the reaction medium through one or more portals.

(57) Abstract

A procedure for improved temperature control in controlled radical polymerization processes is disclosed. The procedure is directed at controlling the concentrated of the persistent radical in ATRP and NMP polymerizations procedures and the concentrated heard radicáis in a RAFT polymerization process by feeding a reducing agent or radical precursor continuously or intermiUently to the reaction medium through one of more ports.

Institute

Mexican

Property

Industrial of the

SE__ «CM.» »A« «» SOMÍA

PATENT TITLE NO. 338317

Headlines); ATRP SOLUTIONS, INC.

Address: 855 William PittWay, Pittsburgh, Pennsylvania, 15238, USA

Name: IMPROVED CONTROL OVER RADICAL POLYMERIZATION CONTROLLED PROCESSES.

Classification: lnt.CI.8: C08F2 / 04; C08F2 / 38; C08F2 / 40; C08F20 / 00; C08F4 / 42

Inventors): WOJCIECH JAKUBOWSKI JAMFS SPANSWICK

REQUEST

Number:

MX / a / 2013/006381

International filing date:

December 2011

Pafs:

US

PRIORITY

Date:

December 2010

Number:

12/926,780

Validity: Twenty years

Expiration Date: December 7, 2031

The reference patent is granted based on articles · 1to, Z * flucción V, 6 ° fraction lll, and 59 of the Industrial Property Law.

In accordance with article 23 of the Industrial Property Law, this patent has a non-extendable term of twenty years, "effective as of the date of filing of the international application and shall be subject to the payment of the fee to keep the erect. ί I i

Whoever subscribes to this title lace it based on the provisions of articles 6 of sections III and 7 bis 2 of Industrial Property Law (Official Gazette of the Federation (DOF) 06/27/1991, amended on 02 / 08/1994, 10/25/1996, 12/26/1997, 1 (05/1999, 26 / Ot "Oe4; 4S / O6" O ^; WO1 / 2OO6, -í "/ Se" <0e9, WO < W8W®74WfW «4 / ^ 42) '?erlfcótee 7to‘ ¡3 * Section V subsection a), 4th and 12th sections I and lll of the Regulations of the Mexican Institute of Industrial Property (DOF 12/14/1999, amended on 07/01/2002, 07/15/2004, 28 / 07/2004 and 7/09/2007); Articles 1, 3, 4, 5, section V, subsection a), 16 sections I and III and 30 of the Organic Statute of the Mexican Institute of Industrial Property (DOF) 12/27/1999, amended on 10/10/2002, 07/29/2004, 08/04/2004 and 09/13/2007); 1st, 3rd and 5th subsection a) of the Agreement that delegates powers to the Deputy Directors General, Coordinator, Divisional Directors, Regional Directors, Divisional Deputy Directors, Departmental Coordinators ^ other subordinates of the Mexican Institute of Property OF 12/15/1999 , amended on 02/04/2000, 07/29/2004, 08/04/2004 and 09/13/2O07).1 ii ll ί IÍlI i'll '1 —.....

Issue Date: April 12, 2016

THE DIVISIONAL DIRECTOR OF PATENTS

NAHANNY CANAL REYES

Sand! Nc. 550. Floor 1,

Col. Pueblo Santa María Tepepan,

Xochimilco, CP 1S020,

Mexico City

Tel. (55) 53 34 07 00 www.impl scb.mx

MX / 2016/28191

IMPROVED CONTROL OVER CONTROLLED PROCESSES OF

RADICAL POLYMERIZATION

Cross reference to related requests

The present application claims the priority benefit of the United States of America Patent Application No. 12 / 926,780, filed on December 8, 2010, which is a continuation in part of the United States Patent Application No. 12 / 653,937 filed on December 18, 2009, which also claims the benefit in the United States of America Provisional Patent Application No. 61 / 203,387, filed on December 22, 2008. Each of the foregoing related applications are incorporated herein by reference in their entirety.

Technical field of the invention

Three controlled radical polymerization (CRP) processes are currently widely used for the synthesis of high-performance functional materials. These are: Radical Atom Transfer Polymerization (ATRP) including ARGET ATRP (Regenerated Electron Transfer Activators for

Radical Atomic Transfer Polymerization) and / or ICAR ATRP (Indicators for Continuous Regeneration of the Activator for Radical Radical Atom Transfer Polymerization), reversible addition / fragmentation chain transfer (RAFT) and nitroxide-mediated polymerization (NMP). Processes are described to improve levels of control over various CRP processes for (co) radically polymerizable monomers. The improvements focus on defining industrially scalable processes with reduced environmental impact for the three CRP procedures. In the case of radical atom transfer polymerization (ATRP) the improved process is carried out in the presence of few parts per million of a transition metal catalyst complex and a high degree of control is achieved by running the reaction under controlled addition conditions / activation of a radical reducing / initiating agent or radical initiator. In the case of RAFT, total control is enhanced by doing the reaction under controlled conditions of radical initiator addition / activation. The polymerization rate in a nitroxide mediated polymerization is controlled under controlled addition / activation conditions of a radical initiator to control the concentration of the persistent radical.

Background of the Invention

Many high performance materials, particularly segmented copolymers or composite structures, require controlled polymer synthesis from functional monomers using well-defined initiators. [Macromolecular Engineering. Precise Synthesis, Materials Properties, Applications; Wiley- VCH: Weinheim, 2007.] For optimal performance in various applications, materials may also require controlled processing taking into account the size and topology of the phase-separated domains and the dynamics of test response rates.

Access to well-defined block copolymers was opened by Szwarc in the 1950s [Nature 1956, 176, 1168-1169] through the development of living anionic polymerization. The biggest limitation of this technique is its sensitivity to impurities (moisture, carbon dioxide) and even mild electrophiles, which limits the process to a narrow range of monomers. The reaction medium and all components have to be thoroughly purified before polymerization, thus, the preparation of functional block copolymers or other well defined polymeric materials in high purity

It can be quite a challenge. However, anionic polymerization, which was first implemented in an academic environment, quickly adapted on an industrial scale and ultimately led to the mass production of many well-defined block copolymers, such as polystyrene-6-polybutadiene- 6-polystyrene, working as a thermoplastic elastornero. [Thermoplastic Elastomers, 3rd Ed; Hanser: Munich, 2004]

The rapid industrial adaptation of such a challenging technique can be explained by the fact that anionic polymerization was the first, and indeed the only example of a living polymerization process for more than three decades, that allowed for the synthesis of high-performance materials. Well defined previously inaccessible from a very narrow selection of vinyl monomers. However, materials based on modified block copolymers with properties that were desired for many applications, were the main engine for the expansion of anionic polymerization processes. [Ionic Polymerization and Living Polymers; Chapman and Hall, New York, 1993, ISBN 0-412-03661-4.]

From the late 1970s to the early 1990s, living carbocationic polymerization was discovered and optimized. [Adv. Polym. Sci. 1980, 37, 1-144.] However, the process is as sensitive to impurities as anionic polymerization and the range of monomers that can be polymerized from both techniques are mainly limited to non-polar vinyl monomers.

Although many previous attempts have been made to develop controlled radical polymerization (CPR) processes, critical advances were made in the mid-1990s. CRP can be applied to the polymerization of functional monomers, and thus became feasible. the preparation of many site-specific (co) functional polymers under mild conditions. [Materials Today 2005, 8, 26-33 and

Handbook of Radical Polymerization; Wiley Interscience: Hoboken, 2002.] From a commercial point of view, CRP processes can be carried out at convenient temperatures, do not require exhaustive purification of monomers or solvents, and can be carried out in bulk, aqueous solution, emulsion, etc. . CRP enables polymers with molecular composition, predetermined preparation weights, low and controlled polydispersity, and topology. Radical polymerization is much more tolerant of functional groups than ionic polymerization processes and can polymerize

IMPI

INSTITUTO Miuu.g / .uo DE LA Fi'.Oí IElV.ü industrial

a broader range of unsaturated monomers providing materials with site-specific functionality. Furthermore, copolymerization reactions, which are generally challenging for ionic polymerizations due to the large differences in the reactivity rates of monomers under ionic polymerization conditions, are easy to perform using radical-based CRP. This provides an opportunity to synthesize polymeric materials with predetermined molecular weight (MW), low polydispersity (PDI), controlled composition, site specific functionalities, selected chain topology, and composite material structures that can be used to incorporate biological or inorganic species. in the final product.

The three most studied and commercially promising methods for controlling radical polymerization are: nitroxide mediated polymerization (NMP), [Chemical Reviews 2001, 101, 3661-3688] radical atom transfer polymerization (ATRP), [J. Chern. Rev. 2001, 101, 2921-2990; Progress in Polymer Science 2007, 32, 93-146.] And degenerative transfer with dithioesters by reversible addition / fragmentation chain transfer polymerization (RAFT).

[Progress in Polymer Science 2007, 32, 283-351]. Each of these methods is based on establishing a dynamic balance between a low concentration of active propagation chains and a predominant number of inactive chains that are unable to propagate or terminate as a means of extending the life of propagation chains.

The simple four-component Atomic Transfer Radical Polymerization (ATRP) process, shown below in Scheme 1, was discovered by Matyjaszewski at Carnegie Mellon University. He and his collaborators have described ATRP as well as many improvements to the basic ATRP processes which can be applied to some or all of the modalities herein, in a series of patents and patent applications [United States of America patents Us. 5,763,546; 5,807,937; 5763548, 5,789,487; 5,945,491; 6,111,022; 6,121,371; 6,124,411; 6,162,882; 6,624,262; 6,407,187; 6,512,060; 6,627,314; 6,790,919; 7,019,082; 7,049,373; 7,064,166; 7,157,530 and United States of America Patent Application No. 09 / 534,827; International Publication WO 2007/025310 Al and International Applications Nos. PCT / US2004 / Q09905; PCT / US2005 / 007264; PCT / US2005 / 007265; PCT / US2006 / 033152,

IN'5T «jl:

PCT / US2006 / 033792 and PCT / US2006 / 048656], all of which are incorporated herein by reference in their entirety. Based on the number of publications, ATRP has emerged as the preferred process for controlled / living polymerization of (co) radically polymerizable monomers. Commonly, an ATRP process comprises the use of a transition metal complex that acts as a catalyst for the controlled polymerization of (co) radically polymerizable monomers from an initiator with one or more transerible atoms or groups. Suitable initiators are frequently substituted alkyl halides, attached to a low molecular weight molecule with additional non-initiator functionality, a low molecular weight initiator or macroinitiator with two or more transerible atoms or groups, or an inorganic or organic solid material with groups of tied initiators. The transition metal catalyst participates in a repetitive redox reaction making the transition metal complex of lower oxidation state (Mtn / Ligand) removes by homolytic methods a transferable atom or group from an inactive polymer chain or initiator molecule, Pn-X, to form the active species of propagation, P 'n, in an activation reaction with an activation rate kto that spreads at a speed kp before

INSTITUTE N

OF THE ΓΚΟ, 'ΪΙΟΛΟ

INDC'5 fkíÁL

which transition metal complex in higher oxidation state (XMtn + 1/ Ligand) disable the active species of propagation, P 'n, donating again a transferable atom or group to the active end of the chain, speed kgives, not necessarily the same atom or group of the same transition metal complex (Scheme 1).

Pn—X + Mtn/ Logging -— ==== ^ kda p * s + XM,n + 1Logging + M 1 —'i.

Pn ”- Pn

Scheme 1. General mechanism for the ATRP process

The catalyst is not end-chain linked, as in coordination polymerization, and therefore can be used in a controlled / living polymerization process in sub-stoichiometric amounts relative to the initiator. However, as a consequence of radical radical termination reactions, proceeding with a velocity = kt in Scheme 1, forming dead chains Pn- Pm and an excess of XMtn + 1/ Ligand.

Examples of the spectrum of new well-defined polymeric materials prepared using ATRP in the past decade include block copolymers,% TT polymers:

INSJf.

Branches, polymer stars, brushes, and nets, each with predetermined site-specific functionality, as well as hybrids with inorganic or bioconjugated materials. However, their widespread commercial use is still limited. [Chem. Rev. 2007, 107, 2270-2299.] However, these custom-made materials have the potential to improve the performance of a multitude of commercial products in the areas of personal care and cosmetics, detergents and pigments and coatings, thermoplastics, biocompatible materials and drug delivery systems, if a scalable, cost-effective, environmentally friendly process can be defined, surfactants, paints, adhesives, elastomers equivalent

M,

The initially defined normal ATRP process requires a high concentration of catalyst, often approaching 0.1 M in bulk monomer polymerization reactions, commonly concentrations ranging from 0.5% to 1 mol% against monomer, [Handbook of Radical Polymerization; Wiley Interscience: Hoboken, 2002] to overcome the effects of persistent radical ATRP (X / Ligand) accumulation. [Journal of the American Chemical Society n + l

1986, 108, 3925-3927 and Macromolecules 1997, 30, 566611

5672.] The high levels of catalyst employed in the initial ATRP reactions, even those involving more active catalyst complexes, were required to overcome the effects of inevitable increase in the concentration of a catalyst in a higher oxidation state due to the inevitable reactions. radical-radical termination. Since the final reactor product contained between 1,000 and 10,000 ppm of the transition metal complex, the resulting polymer has an intense color and could be slightly toxic. This level of catalyst must be removed from the final polymer before use in most applications. The added production costs associated with the adsorption or removal of the catalyst in addition to the isolation and recycling of organic solvents have slowed down the industrial acceptance of ATRP to produce the materials desired by the market. An additional problem of industrial importance involves the use of the more recently developed highly active (i.e. very reducing) ATRP catalysts. Special handling procedures are often required to remove all oxygen and oxidants from these systems prior to the addition of the rapidly oxidizable catalyst complex. The energy used in this purification process (es) and / or the need for rigorous systems

Deoxygenated contributes to the generation of chemical waste and adds costs. These are the main factors limiting the commercial application of the

ATRP.

Recent advances in ATRP have been described by the inventors herein together with one of the ATRP inventors, K. Matyjaszewski, in International Patent Application No. PCT / US2006 / 048656, published as WO 2007/075817, fully incorporated in the present by reference and which also includes the incorporation of references described herein to define the state of the art in ATRP and definitions of some of the terms used herein. In that application it was described that the concentration of the catalyst used for an ATRP can be reduced to 1-100 ppm by adding a reducing agent, or a free radical initiator, which acts through the reaction to continuously regenerate the activator with the lowest oxidation state from the deactivator with the highest oxidation state that accumulates, Scheme 2. Some suitable reducing agents listed in the incorporated references include: sulfites, bisulfites, thiosulfites, mercaptans, hydroxylamines, amines, hydrazine (N2H4), phenylhydrazine (PhNHNH2), hydrazones, hydroquinone, preservatives

food, flavonoids, beta carotene, vitamin A, atocopherols, vitamin E, propyl gallate, octyl gallate, BHA, BHT, propionic acid, ascorbic acid, sorbates, reducing sugars, sugars comprising an aldehyde group, glucose, lactose, fructose , dextrose, potassium tartrate, nitrites, nitrites [sic], dextrin, aldehydes, glycine and many antioxidants.

Scheme 2. Proposed mechanism for regenerated electron transfer activator for radical polymerization of atom transfer (ARGET ATRP).

This enhancement in ATRP was called ARGET ATRP because the Activator was continuously Re-Generated by Electron Transfer. In Scheme 2 regeneration is carried out by adding a reducing agent but the deactivator can also be reduced by adding a free radical initiator in a

process called ICAR (Initiators for Regeneration

Continuous Activator) ATRP.

These new initiator / catalyst reactivation processes allow the amount of catalyst needed to drive a controlled ATRP to a high conversion of 10,000 ppm used in a traditional ATPR to, in some cases, 10 ppm or less, where removal or Catalyst recycling would be unwarranted for many industrial applications.

Furthermore, the ARGET / ICAR ATRP processes can be started with Cu species11 stable to oxidation, easy to handle and store. Furthermore, the level of control in the described ICAR / ARGET ATRP processes is practically unaffected by an excess (still small amount compared to the initiator) of the reducing agent to continuously regenerate the activator in a lower state of oxidation when / if oxidized in the presence of limited amounts of air. [Langmuir 2007, 23, 4528-4531.]

Chain termination functionality in a normal ATRP can be lost by a combination of radical-radical termination reactions and by side reactions between increasing radicals and the catalyst complex; of

Cu11 (radical oxidation to carbocation) or Cu species11 (reduction of radical to carbanion). Therefore, another important feature of the new ARGET / ICAR catalyst systems is the suppression / reduction of side reactions due to the use of a low concentration of the transition metal complex. Side reactions based on reduced catalysts in ICAR and ARGET ATRP allow synthesizing higher molecular weight polymers and polymers with higher chain termination functionality which can allow the preparation of pure, certainly pure block copolymers.

It was conceived as a simple solid procedure.

In PCT application / US2006 / 048656 reactivator was added to the reaction in a single addition and control was exercised on the reaction by continuous adjustment of KATrp in the presence of excess reducing agent. Successful polymerization was achieved in laboratory-scale 10-50 mL Schlenk flasks for common monomers such as methyl methacrylate (MMA), butyl acrylate (nBA), styrene (St), and acrylonitrile (AN). Successful synthesis of block copolymers from common monomers such as MMA, nBA, MA, and St. was reported.

The critical phrase in the previous paragraph describes the scale at which innovative work was done to define the improved procedures: 10-50 mL. When the procedures outlined in PCT / US2006 / 048656 were scaled up, some critical disadvantages of the process became apparent that accompany the improvements made in the application:

a) slow reactions (especially for methacrylates, stretch us)

b) need for exothermic process (especially for acrylates)

c) the need for precise temperature control

d) limited information to scale and automate the process.

Procedures for overcoming these limitations, particularly on a large scale, are described herein. Indeed, in an embodiment of the invention described, controlled radical polymerization processes, where the rate of addition of a radical reducing / initiating agent is continuously adjusted, allows the conversion of monomer to polymer to exceed 80%, preferably it exceeds 90% and optimally exceeds 95%.

Summary of the invention

One embodiment of the polymerization processes of the present invention is directed to polymerize free radical polymerizable monomers in the presence of a polymerization medium, which initially contains at least one transition metal catalyst, for example, in a relatively high concentration. low, and an atomic transfer radical polymerization initiator. The polymerization medium may additionally contain a reducing agent or a radical and / or ligand initiator. Enough ligand can be added to the reaction medium to modify the solubility and activity of the transition metal catalyst. One or more radical reducing or initiating agents may be added at the start or during the polymerization process in a continuous or intermittent form or it may be activated in an intermittent form. The polymerization process may further comprise reacting the reducing agent with at least one of the transition metal catalysts in an oxidized state further containing a radically transferable atom or group to form a compound that is not significantly involved in the control of the process of polymerization. As a reducing agent it can

employ a transition metal in the zero oxidation state.

Another modality of the described process is directed towards continuous control over the concentration of the persistent radical in an NMP. In this embodiment, the decomposition rate of the initiator added to the reaction in continuous or intermittent mode is selected to match the rate of radical / radical termination reactions that would otherwise accumulate at the concentration of the free stable radical and would reduce the speed of propagation.

A further embodiment of the described process relates to RAFT polymerizations. In a RAFT polymerization the rate of polymerization is controlled by the decomposition rate of the added initiator. Normally all of the initiator is added to the reaction at the start of the reaction and this could cause an increased rate of decomposition of the initiator if the temperature of the reaction is not well controlled in the polymerization vessel during each stage of the reaction. As mentioned for ICAR ATRP, continuous addition of the initiator and verification of the reaction temperature provides information on,

if, and when, the initiator addition should be stopped in order to maintain control over the reaction.

Modes of the polymerization process of the present invention include bulk polymerization processes, polymerization processes performed in a solvent, polymerization processes carried out from solid surfaces, biphasic polymerization processes including emulsion polymerization processes, mini-emulsion polymerization, microemulsion processes, inverted emulsion polymerization processes and suspension polymerization processes. In such biphasic polymerization processes the polymerization processes may further comprise at least one of the following: a suspending medium, a reactant or surfactant, and a monomer phase comprising at least a portion of monomers that can be radically polymerized .

It should be noted that, when used in this specification and the appended claims, the singular forms a, and, and include plural referents unless the context clearly indicates otherwise. Thus, for example, the reference to a polymer may include more than one polymer or copolymers.

ΜΡΙ &

MEXICAN INSTITUTE

CE LA PSOTIEOAD fcS.

INDUSTRIAL

These described procedures provide a means to optimize and automate polymerization processes by exercising continuous control over the activator / deactivator ratio, persistent radical concentration, or initiator concentration present in a

CRP.

The advantages of the described activation / feeding method when the reagent has run out include:

a) use of minor amounts of catalyst and initiator per radical or reducing agent,

b) less need for precise temperature control,

c) higher reaction temperature, which allows higher conversions in a shorter time with fewer solvents,

d) the potential for automation of the entire process, and

e) the development of safe scalable processes for exothermic polymerization reactions, although heat removal is still a requirement.

The expansion resulting from the use of the proposed system for CRP will allow to reduce costs for the purification of products, a significant decrease in waste and improved safety.

providing additional means to control the reaction temperature. Furthermore, the rate of addition of a radical reducing / initiating agent can be continuously adjusted to allow the conversion of monomer to polymer to exceed 80%, preferably exceed 90% and optimally exceed 95%, taking into consideration the viscosity of the medium of reaction and diffusion rate of the added reducing agent.

In the following examples, and the discussion of the examples, ATRP is used as an exemplary CRP, but the procedures, components and ranges described can be applied to NMP and RAFT as indicated above.

In one embodiment, a method is provided for safely operating a large-scale, rapid ICAR ATRP polymerization process consisting of: (a) mixing an unsaturated monomer, an initiator, and a metal catalyst; (b) adding an unactivated reducing agent (including, for example, a thermo-activated or photo-activated reducing agent); (c) maintaining the polymerization process at or above a temperature where the unactivated reducing agent has an activation-dependent ti / 2 value (eg, activation by

temperature or electromagnetic) between 30 s and 30 min, and as an option, ligand.

In another embodiment, a method of polymerizing unsaturated monomers is provided, consisting of: (a) mixing unsaturated monomers with an inactive metal catalyst, an initiator having a transferable atom, and optionally, ligand, wherein the inactive metal catalyst is present in the mixture in an amount of less than 250 ppm, by mass, with respect to the total mixture;

(b) heating the mixture to a reaction temperature; (c) adding to the system a first portion of an unactivated reducing agent to generate an activated reducing agent, where the non-activated reducing agent has an activation-dependent value of ti / 2 of between 3 0 s and 30 min in the reaction conditions (for example, temperature or electromagnetic energy value); (d) reducing the inactive metal catalyst with the activated reducing agent to form an active metal catalyst; (e) transferring the transferable atom with the active metal catalyst, thereby activating the initiator for the addition of the unsaturated monomer; and (f) adding at least an additional portion c ^ the non-activated reducing agent to the mixture to induce further polymerization of the monomer.

unsaturated wherein at least the additional portion is added to the mixture at a point where at least 10, 20 or 30 mol%, has polymerized relative to the amount of unsaturated monomer introduced into the mixture, and where at least one polymer product has a degree of polymerization, with respect to the monomer residues corresponding to the unsaturated monomer, of at least 10, 15, twenty or 25 and the mixture as a whole has a conversion of at least 60 mol% relative to the amount of unsaturated monomer introduced into the mixture.

In another embodiment, the radical polymerization method of an unsaturated monomer is provided, which consists of: (a) polymerizing an unsaturated monomer in a system comprising an initiator, optionally ligand, and a metal catalyst at or above a temperature reaction; (b) adding to the system, at a controlled rate, a first quantity of non-activated reducing agent; and (c) controlling the polymerization rate of the unsaturated monomer by adding to the system, at a controlled rate, an amount

<td>additional</td><td>reducing agent</td><td>not</td><td>activated in</td><td>a point</td>

<td>where when</td><td>minus 10, 20</td><td>or</td><td>30% molar,</td><td>It has been</td>

<td>polymerized</td><td>regarding</td><td>the</td><td>amount of</td><td>monomer</td>

unsaturated introduced to the system; where the reaction conditions are sufficient to activate the non-activated reducing agent.

In certain embodiments, the initiator used in the method may comprise a halide-substituted alkyl initiator.

In certain embodiments, the metal catalyst used in the method may consist of an inactive metal halide catalyst.

In certain embodiments, the metal catalyst used in the method may comprise an active metal halide catalyst.

In another embodiment, a method of making a polymer is provided, consisting of: (a) preparing a reaction mixture comprising a radically polymerizable unsaturated monomer, an initiator, optionally ligand, and an inactive metal catalyst in a molar ratio of the monomer unsaturated to the initiator of 25-5000: 1 and a molar ratio of the catalyst to the initiator of 0.001 to 0.5: 1; and / or where the metallic catalyst is present in the mixture in an amount of

less than 250 ppm, by mass relative to the total mix; (b) heating the reaction mixture to a first temperature; (c) dispensing a portion of non-activated reducing agents (eg, thermo-activated reducing agent) into the heated reaction mixture; (d) allowing an amount of said portion of the unactivated reducing agent to decompose into an activated reducing agent; (e) reducing a portion of the inactive metal catalyst with a portion of the activated reducing agent to form at least one active metal catalyst; (f) activating one or more of the initiators with at least one active metal catalyst to form one or more activated initiators; (g) polymerizing at least one monomer in the presence of one or more initiators activated to extend a polymer chain; and (h) repeating steps (c) - (h) while maintaining the reaction conditions at or above a point that causes the non-activated reducing agent to decompose to form an initiator at a value t1/2 dependent on activation between 30 s and 30 min In certain embodiments, steps (c) - (h) of the method can be practically carried out continuously for a period of at least 2 hours and the non-activated reducing agent can be introduced into stable, continuous, discontinuous, variable, gradient, variable techniques,

increasing, decreasing, increasing followed by decreasing, decreasing followed by increasing and / or their combinations.

In certain embodiments, the unactivated reducing agent (can be, for example, a thermo-activated reducing agent and / or a photo-activated reducing agent), used in the method, can be continuously distributed in the heated reaction mixture and in the course of In the polymerization reaction, the portion can be periodically adjusted in relation to the molar conversion of the unsaturated monomer.

In certain embodiments, the unactivated reducing agent (can be for example a thermo-activated reducing agent and / or a photo-activated reducing agent), used in the method, can be continuously dispensed into a heated reaction mixture and in the course of polymerization reaction time, the portion is periodically adjusted relative to the temperature and viscosity process parameters.

In certain embodiments, the unactivated reducing agent (can be for example a thermo-activated reducing agent and / or a photo-activated reducing agent), used in the

method, can be continuously partitioned into the heated reaction mixture and over the course of the polymerization reaction, the portion is periodically adjusted relative to the molar conversion of the unsaturated monomer, over a time interval, where the time interval is greater than three minutes.

In certain embodiments, the unactivated reducing agent used in the method may not be added until at least 15, 30, 45, or 60% molar conversion of the unsaturated monomer is achieved, relative to the molar amount of the unsaturated monomer.

In certain embodiments, the second temperature used in the method can be at least 10 degrees, for example 12 or 15 degrees warmer than the first temperature.

Brief description of the Figures

The following figures exemplify aspects of the process described, but do not limit the scope of the process to the examples discussed.

Figure 1. Temperature variation within an IL batch reactor during nBA ARGET ATRP. Terms

MEXICAN INSTITUTE OF PROPERTY

INDUSTRIAL

experimental: nBA / DEBMM / CuBr2/ TPMA / Sn (EH) 2=

500/1 / 0.025 / 0.1 / 0.1, in bulk at 60 ° C.

Figure 2. Parameters used by computer simulation of MMA polymerization under a series of reaction conditions. The purpose: to find the optimal conditions for a new method of feeding. Results: the models were built and the simulations were carried out successfully and the optimal conditions for the particular modality were found. Topics of interest: heat transfer, side reactions, catalyst stability, etc. were not taken into account.

Figures 3A-3C. The results of the first computer simulation for the new feeding method for an ICAR ATRP of MMA, where:

Figure 3 A It is a kinetic graph;

Figure 3B shows the increase in molecular weight and decrease in PDI against conversion; and

Figure 3 C It is a trace of the CPG. All simulations made for the experimental conditions: MMA / DEBMM / ufctAí «t¡ ± * l

CuIIBr2 / TPMA / AIBN = 500/1 / 0.025 / 0.025 / 0.05 in bulk at 90 ° C, feeding time of 10 h.

Figure 4 A. Molecular Weight and PDI vs. Conversion for Comparative Example Cl.

Figure 4 B. GPC curves for comparative example Cl.

Figure 5 A. Molecular weight and PDI vs. conversion for Comparative Example C2.

Figure 5 B. CPG trace for comparative example C2.

Figure 6 A. Molecular weight and PDI vs. conversion for Comparative Example C3.

Figure 6 B. GPC curves for Comparative Example C3.

Figure 7 A. Molecular weight and PDI vs. conversion for Comparative Example C4.

Figure 7 B. GPC curves for Comparative Example C4.

Figure 8 A. Kinetic graph for the comparative example

C5.

Figure 8 B. Molecular weight and PDI vs. conversion for Comparative Example C5.

Figure 8 C. GPC curves for Comparative Example C5.

Figure 8 D. Temperature profile for Comparative Example C5.

Figures 9A-9C. MMA polymerization by targeting a low degree of polymerization, where

Figure 9A is a kinetic graph;

Figure 9B shows molecular weight and PDI against conversion; and

Figure 9C are GPC traces for ICAR ATRP of MMA with AIBN feed (experiment 08-006-165). Conditions: MMA / DEBMM / CuBr2 / TPMA / AIBN = 100/1 / 0.005 / 0.025 / -; in bulk [MMA] = 8.9 mol / L, 50 ppm Cu, T = 90 ° C. Slow feed rate: 0.002 molar equivalent of AIBN against DEBMM in 1 h (AIBN in 40 mL of solvent to 850 mL of the reaction solution).

Figures 10A-10C. MMA polymerization setting as a goal a high degree of polymerization, where:

Figure 10 A It is a kinetic graph;

Figure 10B shows molecular weight and PDI against conversion; and

Figure 10C is a GPC trace for ICAR ATRP of MMA with V-70 feed (experiment 08-006-180). Conditions: MMA / DEBMM / CuBr2 / TPMA / V-70 = 1000/1 / 0.05 / 0.1 / -; in bulk [MMA] = 8.9 mol / L, 50 ppm Cu, T = 80 ° C. Slow feed rate: 0.004 molar equivalent of V-70 against DEBMM in 1 h (V-70 in 40 mL of solvent to 850 mL of reaction solution).

Figures 11A-11F. Computer simulation of the polymerization of an n-butyl acrylate, specifically:

Figures 11 AC With AIBN supply, where:

Figure 11 A It is a kinetic graph;

Figure 11B is the molecular weight and PDI against conversion;

AND

Figure 11C They are GPC traces. Conditions for ICAR ATRP of nBA powered by AIBN: nBA / DEBMM / CuBr2 / TPMA / AIBN = 100/1 / 0.005 / 0.005 / -; in bulk [nBA] = 7.0 mol / L, 50 ppm Cu, T = 9 0 ° C. Rapid feed rate: 0.03 molar equivalent of AIBN against DEBMM in 6 h (AIBN in 90 mL of solvent to 1 L of the reaction solution). Comments: simulated polymerization reached 99.2% conversion in 1.7 h (PDI = 1.13; chain termination functionality = 99%); there is a short indication period but the reaction was very fast and well controlled; the amount of AIBN added after 1.7 h was 0.0086 mol equivalent against initiator; and

Figures 11 DF without AIBN supply, where:

Figure 11D is the kinetic graph;

Figure 11E is the molecular weight and PDI against conversion;

AND

Figure 11F They are GPC traces. Conditions for ICAR ATRP of nBA without AIBN power: nBA / DEBMM / CuBr2 / TPMA / AIBN = 100/1 / 0.005 / 0.005 / 0.03; in bulk [nBA] = 7.0 mol / L, 50 ppm Cu, T = 90 ° C. Comments:

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INDUSTRIAL

simulated polymerization achieved 99.2% conversion in 28 minutes (PDI = 1.38; chain termination functionality = 99%); polymerization was extremely rapid and produced a polymer with a relatively wide molecular weight distribution (PDI = 1.6 - 2.2 for low conversions).

Figure 12 A. Kinetic graph for Example 2A.

Figure 12 B. Molecular weight and PDI vs. conversion for Example 2A.

Figure 12 C. GPC curves for Example 2A.

Figure 12 D. Temperature profile for Example 2A.

Figures 13A-13C. ICAR polymerization of nBA using V-70 for ICAR ATRP of nBA with V-70 feed (experiment WJ-08-0006-194), where:

Figure 13A is the kinetic graph for Example 2B;

Figure 13B is the molecular weight and PDI against conversion for Example 2B; and

Figure 13C are GPC traces for Example 2B. Conditions: nBA / DEBMM / CuBr2 / TPMA / V-70 = 1000/1 / 0.05 / 0.1 / -; in bulk [nBA] = 6.67 mol / L, 50 ppm Cu, T = 7 0 ° C. Slow feed rate: 0.002 molar equivalent of V-70 against DEBMM in 1 hr (V-70 in 40 mL of solvent to 850 mL of reaction solution).

Figure 14. Running temperature profile WJ-08-006194 (Example 2B).

Figures 15A-15C. ICAR polymerization of styrene (for WJ-08-006-194), where:

Figure 15 A It is a kinetic graph;

Figure 15 B shows molecular weight and PDI against conversion; and

Figure 15 C are GPC traces for ICAR ATRP from St with AIBN feed (experiment WJ-08-006-192). Conditions: St / DEBMM / CuBr2 / TPMA / AIBN = 100/1 / 0.005 / 0.1 / 0.005; in the bulk [St] = 8.31 mol / L, 50 ppm Cu, T = 100 ° C. Slow feed rate: 0.008 molar equivalent of AIBN vs. DEBMM in 1 hr (AIBN

in 40 mL of solvent to 850 mL of the reaction solution).

Figures 16A and 16B. St polymerization (high DP) (experiment WJ-08-006-193). Process automation, where:

Figure 16A is a kinetic graph; and

Figure 16B is the temperature profile. St ICAR ATRP with AIBN feed (experiment WJ-08-006-193). Conditions: St / DEBMM / CuBr2 / TPMA / AIBN = 1000/1 / 0.05 / 0.15 / 0.025; in bulk [St] = 8.31 mol / L, 50 ppm Cu, T = 100-110 ° C. Slow feed rate: 0.008 molar equivalent of AIBN against DEBMM in 1 h (AIBN in 40 mL of solvent to 850 mL of reaction solution).

Figures 17A and 17B. Kinetics for ICAR ATRP of St with feeding of AIBN (experiment WJ-08-006-193) establishing a high DP objective, where:

Figure 17A is the molecular weight and PDI against conversion; and

IMPI / 77

INSTIT 'DE ί

I.'sluSTXML

Figure 17B are GPC traces. Conditions: St / DEBMM / CuBr2 / TPMA / AIBN = 1000/1 / 0.05 / 0.15 / 0.025; in bulk [St] = 8.31 mol / L, 50 ppm Cu, T = 100110 ° C. Slow feed rate: 0.008 molar equivalent of AIBN against DEBMM in 1 h (AIBN in 40 mL of solvent to 850 mL of reaction solution).

Description of the embodiments of the invention

The term hydrophilic is understood to mean, relative to a material, such as a polymeric arm or a polymeric segment of a polymeric arm, that the material is water soluble and comprises hydrophilic segments having an HLB (hydrophilic-lipophilic balance) equal to or greater than 8, for example, an HLB equal to 16-2 0, or equal to or greater than 18, 19, or 19.5. In certain embodiments, the hydrophilic segment may comprise at least 75 mol% of water soluble monomer residues, for example, between 80 mol% to 100 mol% or at least 85 mol%, 90 mol%, 95 mol%, or when minus 97 mol% of water soluble monomer residues.

The term hydrophobic is understood to mean, in relation to a material, such as an arm

polymeric or a polymeric segment of a polymeric arm, that the material is insoluble in water and comprises hydrophilic segments having HLB less than 8, for example, an HLB less than 7. In certain embodiments, the hydrophobic segment may comprise at least 75% mol of water insoluble monomer residues, for example between 80 mol% to 100 mol% or at least 85 mol%, 90 mol%, 95 mol%, or at least 97 mol% of water insoluble monomer residues.

The term monomer residue or monomeric residue is understood to mean the residue resulting from the polymerization of the corresponding unsaturated monomer. For example, a polymer derived from the polymerization of an acrylic acid monomer (or derivatives thereof, such as acid protected derivatives, with acrylic acid, including, but not limited to methyl ester or butyl ester of acrylic acid), will provide segments Polymers, identified as PAA, comprising repeat units of acrylic acid monomeric residues, i.e. -CH (CO2H) CH2-. For example, a polymer derived from the polymerization of sterol monomers will provide polymeric segments, identified as PS, which comprise sterol monomeric residue repeating units, i.e.

iÁ feoFiisc / ,?

JBüSVítiAl

-CH (C6H5) CH2-. For example, a polymer derived from the polymerization of monomeric divinylbenzene monomers will provide polymeric segments comprising repeating units of monomeric divinylbenzene residues, i.e., -CH2CH (06¾) CHCH2-.

Suitable unsaturated monomers that may be useful in the reactions and / or formation of (co) polymers, in the various embodiments presented and described in this application, may include, but are not limited to, those selected from protected and unprotected acrylic acid, such as methacrylic acid; ethacrylic acid; methyl acrylate; ethyl acrylate; n-butyl acrylate; iso-butyl acrylate; t-butyl acrylate; 2ethylethyl acrylate; decyl acrylate; octyl acrylate; methyl methacrylate; ethyl methacrylate; n-butyl methacrylate; iso-butyl methacrylate; tbutyl methacrylate; 2-ethylexyl methacrylate; decyl methacrylate; methyl ethacrylate; ethyl ethacrylate; n-butyl ethacrylate; iso-butyl ethacrylate; t-butyl ethacrylate; 2-ethylexyl ethacrylate; decyl ethacrylate; 2,3-dihydroxypropyl acrylate; 2,3-dihydroxypropyl methacrylate; 2hydroxyethyl acrylate; 2-hydroxypropyl acrylate; hydroxypropyl methacrylate; glyceryl monocylate;

IMPI «

C ', -, 0 \ 1 glyceryl monoethacrylate; glycidyl methacrylate; glycidyl acrylate; acrylamide; methacrylamide; ethacrylamide; N-methyl acrylamide; Ν, Ν-dimethyl acrylamide; Ν, Ν-dimethyl methacrylamide; N-ethyl acrylamide; N-isopropyl acrylamide; N-butyl acrylamide; Nt-butyl acrylamide; N, N-di-n-butyl acrylamide; N, N-diethylacrylamide; N-octyl acrylamide; N-octadecyl acrylamide; N, N-diethylacrylamide; N-phenyl acrylamide; N-methyl methacrylamide; N-ethyl methacrylamide; N-dodecyl dimethylaminoethyl acrylamide;

acrylamide methacrylamide;

quaternized;

dimethylaminoethyl quaternized;

methacrylamide; N, NN, N-dimethylaminoethyl N, N-dimethylaminoethyl

N, N-dimethylaminoethyl methacrylamide

N, N-dimethylaminoethyl acrylate; N, N-methacrylate; Quaternized N, N-dimethyl-aminoethyl acrylate; Quaternized N, N-dimethylaminoethyl methacrylate; 2-hydroxyethyl acrylate; 2-hydroxyethyl methacrylate; 2-hydroxyethyl ethacrylate; glyceryl acrylate;

2-methoxyethyl acrylate; 2-methoxyethyl methacrylate; 2methoxyethyl ethacrylate; 2-ethoxyethyl acrylate; 2-ethoxyethyl methacrylate; 2-ethoxyethyl ethacrylate; maleic acid; maleic anhydride and its ester halves; fumaric acid, itaconic acid; itaconic anhydride and its ester halves; crotonic acid, angelic acid; diallyldimethylammonium chloride; vinyl pyrrolidone; vinyl imidazole; methyl vinyl ether; methyl vinyl ketone;

ν ',

ί.'οτ; τ: υ <· maleimide; vinyl pyridine; vinyl pyridine-N-oxide; vinyl furan; styrene sulfonic acid and its salts; allyl alcohol; allyl citrate; allyl tartrate; vinyl acetate; vinyl alcohol; vinyl caprolactam; vinyl acetamide; vinyl formamide; acrylonitrile; and mixtures thereof.

Other suitable unsaturated monomers that may be useful in the reactions and / or formation of the (co) polymers, in the various embodiments presented and described in this application, may include, but are not limited to, those selected from methyl acrylate; methyl methacrylate; methyl ethacrylate; ethyl acrylate; ethyl methacrylate; ethyl ethacrylate; n-butyl acrylate; n-butyl methacrylate; n-butyl ethacrylate; 2-ethylhexyl acrylate 2ethylhexyl methacrylate; 2-ethylhexyl ethacrylate; Noctyl acrylamide; 2-methoxyethyl acrylate; 2hydroxyethyl acrylate; N, N-dimethylaminoethyl acrylate; N, N-dimethylaminoethyl methacrylate; acrylic acid; methacrylic acid; Nt-butylacrylamide; N-secbutylacrylamide; Ν, Ν-dimethylacrylamide; N, N-dibutylacrylamide; N, N-dihydroxiethillacrylamide; 2-hydroxyethyl acrylate, 2hydroxyethyl methacrylate; benzyl acrylate; 4- acrylate

butoxycarbonylphenyl; butyl acrylate; 4cyanobutyl acrylate; cyclohexyl acrylate; dodecyl acrylate; 2-ethylhexyl acrylate; heptyl acrylate; iso-butyl acrylate; 3-methoxybutyl acrylate; 3-methoxypropyl acrylate; methyl acrylate; N-butyl acrylamide; Ν, Ν-dibutyl acrylamide; ethyl acrylate; methoxyethyl acrylate; hydroxyethyl acrylate; diethylene glycolethyl acrylate; acrylonitrile; styrene (optionally substituted with one or more C1-C12 straight or branched chain alkyl groups); alphamethylstyrene; t-butyl styrene; p-methylstyrene; and mixtures thereof.

Suitable hydrophobic unsaturated monomers that may be useful in the reactions and / or formation of (co) polymers, in the various embodiments presented and described in this application, that can be used include, but are not limited to methyl acrylate, acrylate ethyl; n-butyl acrylate; isobutyl acrylate; t-butyl acrylate; 2-ethylhexyl acrylate; decyl acrylate; octyl acrylate; methyl methacrylate; ethyl methacrylate; n-butyl methacrylate, · iso-butyl methacrylate; t-butyl methacrylate; 2-ethylhexyl methacrylate; decyl methacrylate; methyl ethacrylate; ethyl ethacrylate; methacrylate

TV

;; t ι.λ ι

n-butyl; iso-butyl ethacrylate; tbutyl ethacrylate; 2-ethylhexyl ethacrylate; decyl ethacrylate; 2,3-dihydroxypropyl acrylate; 2,3dihydroxypropyl methacrylate; 2-hydroxypropyl acrylate; hydroxypropyl methacrylate; glycidyl methacrylate; glycidyl acrylate; acrylamides; styrene; styrene optionally substituted with one or more C1-C12 straight or branched chain alkyl groups; or alkyl acrylate. For example, the hydrophobic monomer can comprise sterile; α-methylstyrene; t-butyl styrene; pmethylstyrene; methyl methacrylate; or t-butyl acrylate. For example, the hydrophobic monomer can comprise styrene. In certain embodiments, the hydrophobic monomer can comprise a protected functional group.

Suitable hydrophilic unsaturated monomers that may be useful in the reactions and / or formation of (co) polymers, in the various embodiments presented and described in this application, that can be used include, but are not limited to, protected acrylic acid and unprotected; such as methacrylic acid, ethacrylic acid; methyl acrylate; ethyl acrylate; n-butyl acrylate; iso-butyl acrylate; t-butyl acrylate; 2-ethylhexyl acrylate; decyl acrylate;

octyl acrylate; methyl methacrylate; ethyl methacrylate; n-butyl methacrylate; isobutyl methacrylate; t-butyl methacrylate; 2-ethylhexyl methacrylate; decyl methacrylate; methyl ethacrylate; ethyl ethacrylate; n-butyl ethacrylate; iso-butyl ethacrylate; t-butyl ethacrylate; 2-ethylhexyl ethacrylate; decyl ethacrylate; 2,3dihydroxypropyl acrylate; 2,3-dihydroxypropyl methacrylate, 2-hydroxyethyl acrylate; 2-hydroxypropyl acrylate; hydroxypropyl methacrylate; glyceryl monoacrylate; glyceryl monoethacrylate; glycidyl methacrylate; glycidyl acrylate; acrylamide; methacrylamide; ethacrylamide; N-methyl acrylamide; Ν, Ν-dimethyl acrylamide; Ν, Ν-dimethyl methacrylamide; N-ethyl acrylamide; N-isopropyl acrylamide; N-butyl acrylamide; Nt-butyl acrylamide; N, N-di-n-butyl acrylamide; N, N-diethylacrylamide; N-octyl acrylamide; N-octadecyl acrylamide; N, N-diethylacrylamide; N-phenyl acrylamide; N-methyl methacrylamide; N-ethyl methacrylamide; N-dodecyl acrylamide; quaternized;

dimethylaminoethyl acrylamide methacrylamide; quaternized;

methacrylamide; N, NN, N-dimethylaminoethyl N, N-dimethylaminoethyl

N, N-dimethylaminoethyl methacrylamide N, N-dimethylaminoethyl acrylate; N, N-dimethylaminoethyl methacrylate; quaternized N, N-dimethyl-aminoethyl acrylate; N, N <methacrylate

!. \ £ ¡JjT'í'ÍAÍ

quaternized dimethylaminoethyl; 2hydroxyethyl acrylate; 2-hydroxyethyl methacrylate; 2-hydroxyethyl ethacrylate; glyceryl acrylate; or 2methoxyethyl acrylate; 2-methoxyethyl methacrylate; methacrylate

2-methoxyethyl; 2-ethoxyethyl acrylate; methacrylate

2-ethoxyethyl; 2-ethoxyethyl ethacrylate; maleic acid; maleic anhydrous and its semi-esters; fumaric acid; itaconic acid; itaconic anhydrous and its semi-esters; crotonic acid; angelic acid; dialidimethyl ammonium chloride; vinyl pyrrolidone vinyl imidazole; methyl vinyl ether; methyl vinyl ketone; maleimide; vinyl pyridine; vinyl pyridine-N-oxide; vinyl furan; Styrene sulfonic acid and its salts, allyl alcohol; allyl citrate; allyl tartrate, vinyl acetate; vinyl alcohol; vinylcaprolactam; vinyl acetamide; or vinylformamide. For example, the hydrophilic unsaturated monomer can comprise protected and unprotected acrylic acid, such as methacrylic acid, ethacrylic acid; methyl acrylate; ethyl acrylate; n-butyl acrylate; iso-butyl acrylate; t-butyl acrylate; 2-ethylexyl acrylate; decyl acrylate; octyl acrylate; methyl acrylate; methyl methacrylate; methyl ethacrylate; ethyl acrylate; ethyl methacrylate; ethyl ethacrylate; n-butyl acrylate; n-butyl methacrylate; n-butyl ethacrylate;

2-ethylhexyl acrylate; 2-ethylexyl methacrylate; 2-ethylexyl ethacrylate; N-oxyl acrylamide; acrylate

2-methoxyethyl; 2-hydroxyethyl acrylate; N, N-dimethylaminoethyl acrylate; N, N-dimethylaminoethyl methacrylate; acrylic acid; methacrylic acid; Nt-butylacrylamide; N-sec-butylacrylamide; N, N-dimethylacrylamide; Ν, Ν-dibutylacrylamide; N, Ndihydroxyethyl acrylamide; 2-hydroxyethyl acrylate; 2-hydroxyethyl methacrylate; benzyl acrylate; 4-butoxycarbonylphenyl acrylate; butyl acrylate; 4-cyanobutyl acrylate; cyclohexyl acrylate; dodecyl acrylate; 2-ethylexyl acrylate; heptyl acrylate; iso-butyl acrylate; 3methoxybutyl acrylate; 3-methoxypropyl acrylate; methyl acrylate; N-butyl acrylamide; Ν, Ν-dibutyl acrylamide; ethyl acrylate; methoxyethyl acrylate; hydroxyethyl acrylate; or diethylene glycol ethyl acrylate. For example, the hydrophilic unsaturated monomer can consist of protected and unprotected acrylic acid; such as methacrylic acid; ethacrylic acid; methyl acrylate; ethyl acrylate; n-butyl acrylate; iso-butyl acrylate; t-butyl acrylate; 2-ethylhexyl acrylate; decyl acrylate; octyl acrylate; 2-hydroxyethyl acrylate; N-isopropylacrylamide; ethylene glycol methacrylate; (polyethylene glycol) methacrylate; or

ΙΝ'ΤΠυ

I '

'.Λ, - /// 7 quaternized dimethylaminoethyl methacrylate. For example, the hydrophilic unsaturated monomer can consist of acrylic acid, such as methacrylic acid; 2-hydroxyethyl acrylate; acrylamide; vinyl pyrrolidone; vinyl pyridine; styrene sulfonic acid; PEGmethacrylate; 2- (dimethylamino) ethyl methacrylate; 2- (trimethylamino) ethyl methacrylate; 2-acrylamido-2-methylpropansulfonic acid. For example, the hydrophilic monomer may consist of acrylic acid.

Suitable metal catalysts that may be useful in the reactions and / or formation of (co) polymers, in the various embodiments presented and described in this application, may include metals such as transition metals, such as Cu, which can be converted to a metal. oxidized in situ and / or those represented by Formula (I):

Formula (I) Mt+ nX '

<td>where</td><td>Mt+ n can understand</td><td>Cu+1 ;</td><td>Cu+2 ;</td><td>Faith+2 ;</td><td>Faith+3 ;</td><td>Ru+2</td>

where X 'may consist of halogen; Ci-C alkoxy6-; (SO4) i / 2; (PC> 4) i / 3; (R1PO4) i / 2; (R ^ PC ^); triflate; hexafluorophosphate; methanesulfonate; arylsulfonate; CN; and R2CO2; where R1 may comprise aryl or Ci-C alkyl group2or linear or branched, such as C1-C10 alkyl group, or where two R groups1 they can join to form a 5-, 6- or 7-membered heterocyclic ring; where R2 it may comprise hydrogen or straight or branched C1-C6 alkyl group which can be substituted 1 to 5 times with a halogen; and where n is the formal charge on the metal (0 n 7).

The metal catalyst can be a metal halide catalyst, where the metal halide catalyst can be present in an active or an inactive form. For example, an inactive metal halide catalyst may comprise a metal that has a higher oxidation state than a metal of a corresponding active metal halide catalyst. The inactive metal halide catalyst can be considered as a precursor form of an active metal halide catalyst.

Suitable inactive metal halide catalysts that may be useful in the reactions and / or formation of

(co) polymers, in the various embodiments presented and described in this application, may include, but are not limited to, those comprising transition metals, such as copper, iron and ruthenium, and one or more halides, such as chloride, bromide , iodide, or combinations thereof. For example, the inactive metal halide catalyst may be copper (II) halide, such as copper (II) chloride, copper (II) bromide, or copper (II) iodide.

Suitable active metal halide catalysts that may be useful in the reactions and / or formation of the (co) polymers, in the various embodiments presented and described in this application, may include, but are not limited to, those that comprise transition metals , such as copper, iron, and ruthenium, and one or more halides, such as chloride, bromide, iodide, or combinations thereof. For example, the active metal halide catalyst may be copper (I) halide, such as copper (I) chloride, copper (I) bromide, or copper (I) iodide.

For example, an inactive metal halide catalyst, such as copper (II) bromide, can participate in a repetitive redox reaction to form an active metal halide catalyst, such as copper (I) bromide,

whereby the active metal-halide catalyst, optionally comprising one or more Iigands, can homolytically remove an atom or group that is transferable from an initiator molecule and / or inactive polymer chain (Pn-X), to form an active propagating species, Pn*, in an activation reaction with an activation rate kto that can be propagated with a speed kp to an inactive metal halide catalyst, such as a transition metal complex in a higher oxidation state (XMtn + 1/ Ligand) deactivates the active propagating species, Pn*, donating back a transferable atom or group to the active end of the chain, speed kdto (although not necessarily the same atom or group of the same transition metal complex). (Scheme 1)

Suitable ligands that may be useful in the reactions and / or formation of (co) polymers, in the various modalities presented and described in this application, include those that may be capable of complexing with an active metal halide catalyst may include, but is not limited to, tris (2pyridylmethyl) amine (TPMA); tris [2- (dimethylamino) ethyl] amine (Me6TREN); N, N, N ', N, N-pentamethyldiethyltriamine (PMDETA); N, N, N ', N, N', N'-hexamethyltriethylenetetramine

(ΗΜΤΕΤΑ); 4,4'-dinonyl bipyridine (dNbipi); or bipyridine (beep).

Other suitable ligands that may be useful in the reactions and / or formation of the (co) polymers, in the various embodiments presented and described in this application, may include, but are not limited to compounds having the formulas:

Formula (II) R3-ZZ4

Formula (III) R3-Z- (R5-Z)m-R4 where R3 and R4 they are independently selected from the group comprising hydrogen; Ci-C alkyl2or; aryl; heterocyclyl and Ci-C alkyl6 substituted with Ci-C alkoxy6; Ci-C dialkylamino4; C (= Y) R7, C (= Y) R8 R9, and

YC (= Y) R10, where Y can be NR10 or O, where R7 it can be Ci-C2o-alkyl, C1-C20-alkoxy, aryloxy or heterocyclyloxy, and where R8 and R9 independently they are hydrogen or Ci-C2oz alkyl or R and R9 can join together to form a C alkylene group2-C5, thereby forming a 3 to 5-membered ring, and

where R10 is hydrogen, linear or branched Ci-C alkyl or aryl20;

where Z can be O, S, NR6 or PR6, where R6 can be3 and R4, and where Z can be PR5, where R6 may * 7 be Ci-C alkoxy2or;

where each R7 independently it may be a divalent group selected from the group consisting of C3-C3 cycloalkaryl, C cycloalkaryl3-C8, arendiyl or heterocyclylene, where the covalent bonds for each Z can be in the neighborhood positions, and C alkylene2-C4 and C alkylene2-C4 where the covalent bonds for each Z are in neighborhood positions or in β positions; and m is from 1 to 6.

For example, the compounds of Formulas (II) or (III) can comprise an R3 and R4 which can bind to form a saturated or unsaturated heterocyclic ring. The compounds of Formulas (II) or (III) can comprise compounds where each of R3-Z and R4, form a ring with group R5 to which Z can bind to form an attached heterocyclic ring system or

merged. The compounds of Formulas (II) or (III) can comprise compounds where one or both of R3 and R4 they can be heterocyclic, and where Z can be a covalent bond; CH2; a ring with 4 to 7 members fused to R3 or R4 or both; CO; porphyrins or porphycenes, which may be substituted with from 1 to 6 halogen atoms; Ci-C6 alkyl groups; Ci-C alkoxy groups6; Ci-Ce alkoxycarbonyl; aryl groups; heterocyclyl groups; or C1-C6 alkyl groups further substituted with from 1 to 3 halogens.

Formula (IV) R11 R12 C (C (= Y) R7)2 where Y and R7 are as defined above, and where each of R11 and R12 they can be independently selected from the group comprising hydrogen; halogen; Ci-C20 alkyl; aryl; or heterocyclyl; and where R11 and R12 can join to form a C3-Cg cycloalkyl ring or a hydrogenated aromatic ring or ra-t

IN;

heterocyclic, any of which (except for hydrogen and halogen) can be further substituted with 1 to 5 Ci-C alkyl groups6, Ci-C alkoxy groups6, halogen atoms, aryl groups, or combinations thereof; and cyclopentadienyl ligands and arends, wherein the cyclopentadienyl ligands can be substituted with from 1 to 5 methyl groups, or can be linked through an ethylene or propylene chain to a second cyclopentadienyl ligand.

The term "initiator" is understood to mean a molecule comprising one or more transferable atoms or groups, wherein the initiator is capable of decomposition to provide activated species capable of reacting with unsaturated monomers to form polymeric components. For example, the initiator may be an alkyl-containing molecule containing one or more transferable atoms or groups, such as a halide-substituted alkyl initiator, where the halide is the transferable atom or group.

Suitable initiators that may be useful in the reactions and / or formation of the (co) polymers, in the various embodiments presented and described in this application, may include, but are not limited to, halides.

MEXICAN INSTITUTE

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IN'OUS f.TI.U

alkyl or substituted alkyl halides, such as diethyl 2bromo-2-methylmalonate (DEBMM); Ethyl 2-bromoisobutyrate (EBiB); Methyl 2-bromopropionate (MBP); Ethyl 2-chloroisobutyrate (ECiB); 1,2bis (2-bromoisobutyryloxy) ethane (2f-BiB); a lower molecular weight initiator comprising one or more transferable atoms or groups, such as a substituted alkyl halide added to a lower molecular weight molecule, or a substituted alkyl halide added to a lower molecular weight molecule that does not have a additional non-initiating functionality; a macroinitiator having one or more transferable atoms or groups, such as a polymeric component comprising an alkyl halide moiety, for example, a polystyrene block having a halide at one terminal end; a solid inorganic material with attached starter groups; or an organic material with attached starter groups.

Other suitable initiators that may be useful in the reactions and / or formation of the (co) polymers, in the various embodiments presented and described in this application, may include, but are not limited to, having Formula (V):

Formula (V) R13 R14 R15 CX where X comprises Cl, Br, I, OR16, MR1, To be1, OP (= O) R1, OP (= O) (OR ^ z, OP ^ OJOR1, O-NÍR ^ zy S- (= S) N (R1) 2, where R16 is alkyl with from 1 to 2 0 carbon atoms in which each of the hydrogen atoms can be independently replaced by halide, R1 is aryl or a linear or branched Ci-C20 alkyl group, and where a NÍR ^ z group is present, the two R groups1 they can join to form a 5- or 6-membered heterocyclic ring; and where R13, R14, and R15 are each independently selected from the group consisting of hydrogen, halogen, Ci-C20 alkyl, C cycloalkyl3-C8, X (= Y) R7, C (= Y) NR8 R9, COCI, OH, CN, C alkylene2-C2Q, C2-C20 alkynyl oxyranyl / glycidyl, aryl, heterocyclyl, aralkyl, aralkenyl, Ci-C alkyl6 wherein from 1 to all hydrogen atoms are replaced with halogen and C1-C6 alkyl substituted with from 1 to 3 substituents selected from the group consisting of C1-C4 alkoxy, aryl, heterocyclyl, C (= Y) R, C (= Y) NR8 R9, oxiranyl and glycidyl;

where R7 it is alkyl of 1 to 20 carbon atoms, alkoxy of 1 to 20 carbon atoms, aryloxy or heterocyclyloxy; and R8 and R9 are independently hydrogen or C 1 -C 20 alkyl, or R8 and R9 they can join together to form an alkylene group of 2 to 5 carbon atoms, thereby forming a 3-6 membered ring; so that no more than two R13, R14 and R15 they are hydrogen.

The term activated reducing agent is understood to mean an agent capable of donating one or more electrons to reduce an inactive metal catalyst to form an active metal catalyst. For example, the activated reducing agent, such as a radical-containing species, can be formed from decomposition of a radical initiator, for example, thermal decomposition of a heat-activated radical initiator to form a radical-containing species or photodecomposition of a photo-activated radical initiator to form a radical-containing species. The activated reducing agent can initiate and / or perpetuate a polymerization reaction, such that an ATRP polymerization reaction and / or an ICAR ATRP polymerization reaction, generating or regenerating the active metal catalyst from the inactive metal catalyst (see Scheme 2).

The some suitable activated reducing agents that may be useful in the reactions and / or formation of the (co) polymers, in the various modalities presented and described in this application, may include, but are not limited to, the species of radicals generated to from the decomposition of azo-containing compounds, such as 2,2'-azobis (2-methylpropionitrile (AIBN); a peroxide, | for example, benzoyl peroxide (BPO), lauroyl peroxide or cyclohexanone peroxide; a peroxy acid, for example, peroxyacetic acid or peroxybenzoic acid; tert-butyl peracetate; l, l-bis (terbutylperoxy) -3,3,5- (dibutylphthalate) trimethylcyclohexane;

2,21-azobis (4-methoxy-2.4-dimethyl valeronitrile) (V-70); 2,2'-azobis (2,4-dimethyl valeronitrile) (V-65); Dimethyl 2,2'azobis (2-methylpropionate) (V-601); 2.2 '(V-59);

1,1 'azobis (2-methylbutyronitrile) azobis (cyclohexan-1-carbonitrile) (V-40); 2,2'-Azobis [N (2-propenyl) -2-methylpropionamide] (VF-096); or derivatives or combinations thereof. Other activated reducing agents that may be useful in the reactions and / or formation of (co) polymers, in the various modalities presented and described in this application, may include, but are not limited to, the radical species generated from the breakdown of acetophenone; anisoin; anthraquinone; the sodium salt of hexafluorophosphate dibenzosuberenone;

INDUSTRIAL

anthraquinone-2-sulfonic acid monohydrate; (benzene) tricarbonylchrome; benzyl; benzoin ethyl ether; 4benzoylbiphenyl; 2-benzyl-2- (dimethylamino) -4'morpholinbutyrophenone; 4,4'-bis (diethylamino) benzophenone;

camphorquinone; 2-chlorothioxanthan-9-one; (eumene) cyclopentadienyl iron (II);

2,2-diethoxyacetophenone; 4,4'dihydroxybenzophenone; 2,2-dimethoxy-2-phenylacetophenone; 4 (dimethylamino) benzophenone; 4,4'-dimethylbenzyl; 2,5dimethylbenzophenone; 3,4-dimethylbenzophenone; 4'2-ethylanthraquinone; ferrocene; 3'4'-hydroxyacetophenone; 34-hydroxybenzophenone; 1phenyl ketone; 2-hydroxy-22-methylbenzophenone; 3methylbenzophenone; methibenzoyl format; 2-methyl-4 '~ (methylthio) -2-morpholinpropiophenone; phenanthrenquinone; 4'phenoxyacetophenone; thioxanthan-9-one); or derivatives or combinations thereof.

ethoxyacetophenone; hydroxyacetophenone; hi droxibenzo f enona; hydroxycyclohexyl 15 methylpropiophenone;

Other suitable activated reducing agents that may be useful in the reactions and / or formation of the (co) polymers, in the various embodiments presented and described in this application, may include, but are not limited to, the radical species comprising

IMP I

MEXICAN INSTITUTE OF INDUSTRIAL PROPERTY

hydroxyl radical (H0 '); acloxy radical, such as substituted alkoxy radical (R0 '); acid peroxy radical, such as substituted peroxy acid radical (R (CO) OO '); nitrous radical (R2N0 '); where R independently may represent a Ci-C alkyl group2oo substituted alkyl group; aryl or substituted aryl, or heteroaryl or substituted heteroaryl.

or break down to a transformation

The term "unactivated reducing agent" is understood to mean a precursor agent that decomposes from an activated reducing agent. For example, an unactivated reducing agent can be decomposed, such as thermally photochemical decomposition, or subjected to chemistry, to form an activated reducing agent. For example, a suitable non-activated reducing agent that may be useful in the reactions and / or formation of (co) polymers, in the various modalities presented and described in this application, may include those that decompose to form an activated reducing agent. , such as a hydroxyl radical (HO '); alkoxy radical, such as a substituted alkoxy radical (RO '); peroxy radical acid, such as a substituted peroxy radical acid (R (CO) OO '); radical nitrous (R2NOT'); where R independently can represent an alkyl group of

Ci-C2oo substituted alkyl group; aryl or substituted aryl, or substituted heteroaryl or heteroaryl.

Other non-activated reducing agents that may be useful in the reactions and / or formations of the (co) polymers, in the various embodiments represented and described in this application, may include, but are not limited to, azo-containing compounds such as 2 , 2'azobis (2-methylpropionitrile) (AIBN); a peroxide, for example benzoyl peroxide (BPO); lauroyl peroxide or cyclohexanone peroxide; a peroxy acid, for example, peroxyacetic acid or peroxybenzoic acid; tert-butyl peracetate; 1,1-bis (tert-butylperoxy) -3,3,5 (dibutyl phthalate) trimethylcyclohexane; 2,2'-azobis (4methoxy-2.4-dimethyl valeronitrile) (V-70); 2,2'azobis (2,4-dimethyl valeronitrile) (V-65); Dimethyl 2,2'-azobis (2-methylpropionate) (V-601); 2,2'-azobis (2-methylbutyronitrile) (V-59); 1,1'-azobis (cyclohexane-1carbonitrile) (V-40); 2,2'-Azobis [N- (2-propenyl) -2-methylpropionamide] (VF-096); or derivatives or combinations thereof. Other suitable reducing agents that may be useful in the reactions and / or formation of the (co) polymers, in the various embodiments presented and described in this application, may include, but are not limited to, acetophenone; anisoin; anthraquinone; the salt of "Tser ^ Vafc". · j,

M, .l '* jA. Av

ΤΓ í

INST-TUTU λ'.Γ CA NO OF THE FKC-rJEO ^ D

INDUSTRIAL

anthraquinone-2-sulfonic acid monohydrate sodium; (benzene) tricarbonylchromium; benzyl; benzoin ethyl ether; 4-benzoylbiphenyl; 2-benzyl-2- (dimethylamino) -4'morpholinobutyrophenone; 4,4'-bis (diethylamino) benzophenone; camphorquinone; 2-chlorothioxanthan-9-one; (eumene) cyclopentadienyl iron (II) hexafluorophosphate; dibenzosuberenone; 2,2-diethoxyacetophenone; 4,4'dihydroxybenzophenone; 2,2-dimethoxy-2-phenylacetophenone; 4 (dimethylamino) benzophenone; 4,4'-dimethylbenzyl; 2,5dimethylbenzophenone; 3,4-dimethylbenzophenone; 4'ethoxyacetophenone; 2-ethylanthraquinone; ferrocene; 3 hydroxy acetophenone; 4'-hydroxyacetophenone; 3-hydroxybenzophenone; 4-hydroxybenzopheone; 1-hydroxy cyclohexyl phenyl ketone; 2-hydroxy-2-methylpropiophenone;

2-methylbenzophenone; 3-methylbenzophenone; methibenzoyl format; 2-methyl-4 '- (methylthio) -2morpholinpropiophenone; phenanthrenquinone; 4'phenoxyacetophenone; thioxanthan-9-one); or derivatives or combinations thereof.

The identity of the activated reducing agent or the non-activated reducing agent, the timing of when the non-activated reducing agent is added or the activated reducing agent is generated, the rate of addition of the non-activated reducing agent, and the generation rate of the

MEXICAN INSTITUTE

Of the;. PROPERTY

INDUSTRIAL

Reducing agent activated from its unactivated reducing agent precursor may affect one more of the following, including the degree of polymerization of unsaturated monomers used in the polymerization reaction, the temperature of polymerization, the ability to control temperature and / or speed of polymerization, and the ability to scale a polymerization reaction to an industrial scale size reaction.

The term value you/2 Activation Dependent refers to the amount of time it takes, in a particular activation condition (to trigger activation), to decompose half the concentration of unactivated reducing agent in a system.

The term value ti /2 Temperature dependent refers to the amount of time it takes, at a particular temperature, to decompose half the concentration of non-activated reducing agent in a system, such as thermally decomposing, to form an activated reducing agent. The term value ti /2 Light-dependent refers to the amount of time it takes, with a particular electromagnetic exposure (for example, light or radiation), to break down the ι

half the concentration of unactivated reducing agent in a system, such as a photochemical decomposition, to form an activated reducing agent. The values you/2 Temperature dependent (or light dependent) may be similar to or greater than the time to mix, homogeneously (or homogeneously), the non-activated reducing agent in the polymerization reaction system. Values you/2 temperature dependent (or photo dependent) suitable of an unactivated reducing agent to decompose and form an activated reducing agent, which may be useful in the reactions and / or formation of (co) polymers, in the various modalities presented and described in this request, may include, but are not limited to ti / values2 between 30 s and 30 min, at a particular temperature (or electromagnetic exposure), for example, ti /2 between 1 min and 30 min, such as between 1.5 min and 30 min; between 2 min and 30 min; between 3 min and 30 min; between 4 min and 30 min; between 5 min and 30 min; between 6 min and 30 min; between 7 min and 30 min; between 8 min and 30 min; between 9 min and 30 min; between 10 min and 30 min; between 1 min and 25 min; between 1 min and 20 min; between 1 min and 15 min; between 1 min and 10 min; between 1 min and 5 min; between 30 sec. and 20 min; between 30 sec. and 15 min; between 30 sec. and 10 min; between 30 sec. and 5 min; between 5 min and 25 min; between 5 min and 20 min; between 5 min and 15 min;

INDL'STR.'AL

between 5 min and 10 min; or between 10 min and 2 0 min at a particular temperature (or electromagnetic exposure). Values you/2 temperature dependent (or light dependent) suitable of a non-activated reducing agent to decompose, at a particular temperature (or electromagnetic exposure), to form an activated reducing agent, which may be useful in reactions and / or formation of (co) polymers, in the various embodiments presented and described in this application, may include, but are not limited to ti / 2 values less than 30 min, eg less than 25 min, such as less than 20 min; less than 15 min; less than 10 min; less than 9 min; less than 8 min; less than 7 min; less than 6 min; less than 5 min; less than 4 min; less than 3 min; less than 2 min; less than 1 min; or 30 s.

As noted above, although ICAR and ARGET ATRP were successfully applied to the preparation of polymeric materials on a laboratory scale, unexpected problems were encountered when synthesis was carried out on a larger scale. These problems are exemplified by the following discussion which involves scaling the ICAR system but which are also relevant to the ARGET ATRP, RAFT and NMP systems.

Accurate temperature control through the reaction medium is required - if this is not achieved, an increase in temperature will cause the radical initiator present in the system to decompose at a rapid rate and reduce all species. from Cu11 to Cu1. Loss of deactivator Cu11 The system results in uncontrolled polymerization in addition to an exothermic temperature. Furthermore, control over temperature in an exothermic polymerization reaction is challenging large-scale polymerization procedures due to inefficiencies in heat transfer processes in increasingly viscous media. In normal free radical polymerization systems, viscous polymer solutions can give rise to the Trommsdorf effect.

Figure 1 presents a temperature profile that follows the reaction temperature during polymerization in nBA using ARGET ATRP on a 1-liter scale. The stirred reaction mixture was heated to 60 ° C, but due to the exothermic polymerization process, the temperature inside the flask rose above 80 ° C. Polymerization was not well controlled due to overheating. This indicates that the use of an internal cooler (for example, a

cooling) cannot be efficient enough to keep the temperature uniform within a temperature range of 2-3 ° C.

Prolonged reaction times are used in publications discussing ICAR / ARGET, and other CRP systems due to lower temperatures. Lower temperatures are aimed at allowing slow radical generation (ICAR) or slow reaction of the reducing agent added with the Cu complex11 which has been added to the beginning of the reaction producing reaction times longer than desired for an economic industrial process.

Lower temperatures also increase the viscosity of the system and limit the range of monomers that can polymerize to a higher conversion, for example, monomers that form polymers with a glass transition temperature, Tg, near or below the reaction temperature reaching a glassy state to a higher conversion and control is lost.

Lack of easy automation of the entire process - as Figure 1 illustrates, there is no easy way to automate ICAR / ARGET ATRP with iMPyW configuration '

INSTITUTE -· :.ύ i GIVE THE PTOPÍ tÓ -!} INCiJSTRÍAL

Current experimental and the presence of an excess of the initiator by radicals requires good temperature control.

Although small amounts of catalyst and radical initiator (or reducing agent) are used, a further reduction in the amount of copper catalyst and radical initiator is still desired.

Limited accessible molecular weight (MW) of the polymer. For many applications, it is essential to prepare polymers with higher MW; that is, polymers with segments above MW for chain entanglement, therefore it is very important to minimize the effect of side reactions between increasing radicals and the catalyst that limits the achievable MW. The ARGET and ICAR techniques can partially solve this problem due to the use of low catalyst concentration but the problems outlined above with latear reactions associated with transition metals, ligand and reducing agent must be solved by further reducing the concentration of one or more of reagents.

The new method described will mitigate / resolve all the limitations stated above.

The new method depends on continuous, precise control of the Cu ^ / Cu ratio1 during an ICAR / ARGET ATRP, or from the instantaneous concentration of radicals in the RAFT polymerization or from the directed concentration of the persistent radical present in an NMP process, by feeding a radical initiator (or reducing agent) to the polymerization mixture at a controlled rate and optionally using multiple addition portals to evenly distribute the agent throughout the reaction medium. Feeding should occur at such a rate that the amount of the radical initiator (or reducing agent) added or generated can adequately compensate for all termination reactions that have occurred since the last addition and convert only the appropriate amount of Cu11 to Cu1 (Scheme 3a). Therefore, the amount of the radical initiator, or reducing agent, added at any feeding time should be approximately equal to the number of terminated chains (Scheme 3b) formed since the previous addition.

θ5 / J [Cu '] = zf [P,] = k, [Ρ']2one cleft - ktlkp2 b)

Requirement t R1 = R2 radical termination reactions

Cu-X / Ligand

Vel. power R

Radical reducing or initiating agent

Rusty product

Cu'-x / Ligand

1MPJ

MEXICAN INSTITUTE OF THE PROP'E ^ AP INDUSTRIAL

Scheme 3a. Equation used to calculate the number of chains finished

Scheme 3b. Diagram showing the requirements for controlled atom transfer radical polymerization under feeding conditions by exhaustion of the reducing agent or radical initiator.

As described herein, if the initiator or reducing agents are added slowly through the reaction, the amount of excess activator is controlled and any increase in the rate of decomposition or reduction is avoided. If the reaction temperature is to be increased by eventually stopping the addition, the reaction is stopped. Suitable reducing agents are described in the incorporated references.

In contrast to the present ARGET and ICAR procedures, the amount of the initiator added in a single addition may be less than the stoichiometric amount required to reduce all Cu11 present in the reactor at Cu1. This will be accomplished by the presence, or activation, of a very small amount of the residual initiator (or reducing agent) in the reactor at any time. The amount of initiator fed

MEXICAN INSTITUTE OF LA ROPIEDAD

INDUSTRIAL

to the reactor, or generated, can match the amount of completion that occurs since the previous addition / activation. If the temperature increased locally, due to poor heat exchange or local overheating, then the excess reduction of Cu11 to Cu1 it is easily contained and limited to only the amount of the initiator present locally in the reaction medium. Thus, instead of adding the full amount of initiator / reducing agent at the start of the reaction and relying on incidental decomposition rate of the initiator to maintain control, only the reducing agent / initiator will be fed into the system as much , or generated instantaneously, during the entire process while limiting the effect of temperature fluctuations on the rate of Cu reduction11 to Cu1.

If these conditions are met, the conditions of exhaustion of the reducing agent or radical initiator will be reached during the polymerization process and the proportion Cu will be11 to Cu1 constant, desired. A high enough amount of Cu11 is a requirement for the production of (co) polymers with narrow molecular weight distribution in a controlled ATRP process, equation 1:

INSTiTiíl

C'í

In a process mode after the desired Cu ratio is reached11 to Cu1 only a very small amount of the radical initiator (or reducing agent) would be present instantly in any volume fraction in the polymerization system. As a result, the proportion of Cu11 to Cu1 will be kept within the appropriate range to produce polymers with narrow molecular weight distribution, equation 1.

Many advantages accrue from the new feed method as a result of keeping the instantaneous concentration of the radical initiator (or other reducing agent) in the polymerization system very low.

There is no need for precise temperature control - the only requirement will be to keep the temperature high enough to quickly decompose the added radical initiator, while still allowing sufficient time for the initiator to be distributed through the targeted volume of the reaction mixture afterwards. of addition. Multiple additional ports can be used for large-scale industrial equipment to minimize the time required for

IMPI

MEXICAN INSTITUTE OF INDUSTRIAL PROPERTY

diffusion of the activator to all parts of the reaction medium or only enough light pulsed into the reactor to decompose the required amount of photosensitive initiators.

Safe processes for exothermic reactions - the effect of an exothermic reaction will be diminished by a very low instantaneous concentration of the radical initiator (or reducing agent) since the small amount of the initiator / reducing agent added cannot exceed the excess Cu11 present in the reactor. This means that in the absence of added initiator / activator only a controlled ATRP reaction can occur and this reaction will slow down if an increased concentration of Cu is generated.11 by termination reactions, since excess Cu11 It acts to increase the rate of deactivation of any growing radical chain.

Shorter reaction times - due to the use of higher reaction temperatures, reactions can be much faster since the constant speed of propagation increases the temperature much more than that of the termination, thus retaining a high molar fraction of chains living. The temperature of

ΙΜΡΙί + 3

MEXICAN INSTITUTE ti '

DE í To you. '' '' 'v

'.' I

Higher reaction can also result in lower viscosity systems at any particular conversion, and therefore the reaction can be directed at higher conversion, as well as a higher molecular weight polymer preparation. The monomer to polymer conversion, therefore, can exceed 80%, preferably exceed 90%, and optimally exceed 95%.

Full automation is possible - only small amounts of radical initiator (or reducing agent) are present at any time in the polymerization medium, the reaction should stop as soon as the feed / activation stops. Thus, the rate of polymerization is controlled by the rate of radical generation by decomposition of the initiator by radicals (or by concentration of the reducing agent) and is stopped in any emergency condition simply by incorporating a feedback loop that stops the addition of radical initiator, reducing agent or activation of an added photosensitive initiator.

Continuous feed of the initiator / reducing agent for the purpose of minimizing the steady-state residual concentration of the radical initiator

IM.PI

INSTITUTE vs / · '. ·. · ..; '

DE LA PEOP'PDir, V'A. ~ “L ~ 'índus'kual

thereby reducing the initiator based on side reactions.

Minor amounts of transition metal and ligand are required in the reaction. An excess of ligand used in ARGET and ICAR polymerizations is typically used to counteract the possibility of formation of a monomer / transition metal complex.

Possible control over PDI by increasing the proportion of Cu11 / Cu1 and kp, which depends on the type of monomer and the temperature.

A synthesis in the block of block copolymers, since the greater chain termination functionality is restricted.

The molar% conversion that can be achieved by the polymerization reaction processes described herein can be, but is not limited to, between 165-100 mole% conversion, relative to the initial molar amount of unsaturated monomer introduced into the system. polymerization, wherein the molar% conversion refers to the molar amount of unsaturated monomer converted into the form of a polymer or polymer component. For example, the molar% conversion can be at least 65 molar% conversion, such as up to 100 molar% conversion, eg, up to 99 molar% conversion, or up to 98 molar% conversion; and / or when less than 70%

cool; or at least 98 mol% conversion, relative to the initial molar amount of unsaturated monomer introduced into the polymerization system.

Suitable temperatures to start and / or carry out the polymerization reaction which may be useful in the reactions and / or formation of the (co) polymers, in the various embodiments presented and described in this application, may include, but are not limited to, between 25 ° C and the temperature at which the conversion rate ti /2 is at least 3 0 s (i.e. temperature at you/2= 30 s), for example between 25 ° C and temperature at ti /2 = 1 min, such as between 25 ° C and temperature in you /2 = 2 min; between 25 ° C and temperature in ti / 2 = 3 min; between 25 ° C and temperature in you/2 = 4 min;

between 25 ° C and temperature in you/2 = 5 min; between 25 ° C and

IMP iNSTrrurO

OF THE ; = 'fNL “JSTK temperature in you/2 = 6 min; between 2 5 ° C and temperature in ti / 2 - 7 min; between 25 ° C and temperature in you/2 = 8 min; between 25 ° C and temperature in t2/2 = 9 min; between 25 ° C and temperature in you/2 = 10 min; between 2 5 ° C and temperature in ti / 2 = 15 min; between 25 ° C and temperature in you/2 = 20 min; between 25 ° C and temperature in you /2 = 25 min; or between 25 ° C and temperature in you /2 = 3 0 min

Suitable molar ratios of unsaturated monomers for the initiator that may be useful in the reactions and / or formation of (co) polymers, in the various modalities presented and described in this application, may include, but are not limited to molar ratios of between 25-5,000: 1, for example, between 100-5,000: 1, such as between 250-5,000: 1; between 500-5,000: 1; between

750-5,000: 1; between 1,000-5,000: 1; between 1,500-5,000: 1; between 2,000-5,000: 1; between 2,500-5,000: 1; between 3,0005,000: 1; between 3,500-5,000: 1; between 4,000-5,000: 1; or molar ratios of between 4,500-5,000: 1.

Suitable ratios of inactive metal catalyst to the initiator in the polymerization mixture that may be useful in the reactions and / or formation of the (co) polymers, in the various embodiments presented and described in this application, may include, but are not

INSTITUTO UEX; -.- '») de ¡.Λ PRC PIEDAD

INDUSTRIAL limits to 0.001-0.5: 1, for example, between 0.003-0.5: 1, such as between 0.005-0.5: 1; between 0.007-0.5: 1; between 0.010-0.5: 1; between 0.015-0.5: 1; between 0.020-0.5: 1; between 0.025-0.5: 1; between 0.04-0.5: 1; between 0.05-0.5: 1; between 0.07-0.5: 1; between 0.1-0.5: 1; between 0.15-0.5: 1; between 0.2-0.5: 1; between 0.25-0.5: 1; between 0.3-0.5: 1;

proportions between 0.35-0.5: 1; between 0.4-0.5 molars between 0.45-0.5: 1 and / or the metal catalyst may be present in the mixture in an amount of less than 250 ppm by mass relative to the total mass of the polymerization mixture.

Suitable amounts of metal catalyst that may be useful in the reactions and / or formation of (co) polymers, in the various embodiments presented and described in this application, may include amounts in the range of 0.1 parts per million (ppm) by mass. at 250 ppm by mass relative to the total mass of the polymerization mixture, for example, between 0.1 and 225 ppm, such as between 0.1 and 200 ppm; between 0.1 and 175 ppm; between 0.1 and 150 ppm; between 0.1 and 125 ppm; between 0.1 and 100 ppm; between 0.1 and 75 ppm; between 0.1 and 50 ppm; between 0.1 and 25 ppm; between 0.1 and 20 ppm; between 0.1 and 15 ppm; between 0.1 and 10 ppm; between 0.1 and 5 ppm; between 0.1 and 3 ppm; or amounts between 0.1 and 1 ppm.

INSTITUTE Ι ', ΕΤΖΑί, Ό of the ι ·; .η? Ϊ́ΡΓ>. · .Ο INDUSTRIAL

Suitable proportions of the amount of non-activated reducing agent to the initiator that may be useful in the reactions and / or formation of (co) polymers, in the various modalities presented and described in this application, may include, but are not limited to 0.01 -0.5: 1, for example, between 0.02-0.5: 1, such as between 0.030.5: 1; between 0.04-0.5: 1; between 0.05-0.5: 1; between 0.060.5: 1; between 0.07-0.5: 1; between 0.08-0.5: 1; between 0.090.5: 1; between 0.1-0.5: 1; between 0.2-0.5: 1; between 0.30.5: 1; between 0.4-0.5: 1; or molar relationships between

0.45-0.5:1.

Suitable polymers formed by methods described herein that may be useful in the reactions and / or formation of (co) polymers, in the various embodiments presented and described in this application, may have a molecular weight greater than 100,000 g / mol, for example, between 100,000 g / mol and 2,000,000 g / mol, such as between 125,000 g / mol and 1,750,000 g / mol; between 150,000 g / mol and 1,750,000 g / mol; between 200,000 g / mol and 1,500,000 g / mol; between 225,000 g / mol and 1,250,000 g / mol; between 125,000 g / mol and 1,000,000 g / mol; between 125,000 g / mol and 900,000 g / mol; between 125,000 g / mol and 800,000 g / mol; between 125,000 g / mol and 700,000 g / mol; between 150,000 g / mol and 650,000 g / mol; between 200,000 g / mol and 600,000 g / mol; between 225,000 g / mol and 650,000 g / mol; between

250,000 g / mol and 550,000 g / mol; between 350,000 g / mol and 500,000 g / mol; between 300,000 g / mol and 500,000 g / mol; between 350,000 g / mol and 750,000 g / mol; between 100,000 g / mol and 1,750,000 g / mol; between 100,000 g / mol and 1,500,000 g / mol; between 100,000 g / mol and 1,125,000 g / mol; between 100,000 g / mol and 1,000,000 g / mol; between 100,000 g / mol and 750,000 g / mol; between 100,000 g / mol and 500,000 g / mol; between 100,000 g / mol and 400,000 g / mol; between 100,000 g / mol and 300,000 g / mol; or between 100,000 g / mol and 200,000 g / mol.

Suitable polymers formed by the methods described herein that may be useful in the reactions and / or formation of (co) polymers, in the various embodiments presented and described in this application, may have degrees of polymerization within a polymeric arm of between 10 and 5,000, such as between 10 and 4,500; between 10 and 4,000; between 10 and 3,500; between 10 and 3,000; between 10 and 2,500; between 10 and 2,000; between 10 and 1,500; between 10 and 1,000; between 10 and 900; between 10 and 800; between 10 and 700; between 10 and 600; between 10 and 500; between 10 and 400; between 10 and 300; between 10 and 200; between 10 and 100; between 10 and 75; between 10 and 50; or between 10 and 25.

Suitable copolymers formed by the methods described herein that may be useful in reactions

and / or formation of the (co) polymers, in the various embodiments presented and described in this application, may comprise copolymeric segments having degrees of polymerization of between 10 and 5,000, such as between 10 and 4,500; between 10 and 4,000; between 10 and 3,500; between 10 and 3,000; between 10 and 2,500; between 10 and 2,000; between 10 and 1,500; between 10 and 1,000; between 10 and 900; between 10 and 800; between 10 and 700; between 10 and 600; between 10 and 500; between 10 and 400; between 10 and 300; between 10 and 200; between 10 and 100; between 10 and 75; between 10 and 50; or between 10 and 25.

For example, a suitable copolymer formed by methods described herein that may be useful in the reactions and / or formation of (co) polymers, in the various embodiments presented and described in this application, may comprise copolymeric segments of styrene residues. and acrylic acid residues where the degree of polymerization of the styrene residues can be between 10 and 5,000, such as between 10 and 4,500; between 10 and 4,000; between 10 and 3,500; between 10 and 3,000; between 10 and 2,500; between 10 and 2,000; between 10 and 1,500; between 10 and 1,000; between 10 and 900; between 10 and 800; between 10 and 700; between 10 and 600; between 10 and 500; between 10 and 400; between 10 and 300; between 10 and 200; between 10 and 100; between 10 and 75; between 10 and 50; or between 10 and 25; and where

Jl. -Yes. J¡í_ MEXICAN INSTITUTE OF INDUSTRIAL PROPERTY

the degree of polymerization of the acrylic acid residues can be between 10 and 5,000, such as between 10 and 4,500; between 10 and 4,000; between 10 and 3,500; between 10 and 3,000; between 10 and 2,500; between 10 and 2,000; between 10 and 1,500; between 10 and 1,000; between 10 and 900; between 10 and 800; between 10 and 700; between 10 and 600; between 10 and 500; between 10 and 400; between 10 and 300; between 10 and 200; between 10 and 100; between 10 and 75; between 10 and 50; or between 10 and 25.

Preparing a polymer comprising a degree of polymerization of, for example, comprising styrene residues of between 15 and 5,000, for example, in accordance with the processes described herein can take between 4 to 60 hours, where the polymerization reaction temperature is brought to a temperature where the temperature dependent (or photo dependent) ti / 2 values of an unactivated reducing agent to decompose to form an activated reducing agent may be between 30 sec. and 30 min. Similarly, preparing a polymer comprising a degree of polymerization of, for example, comprising styrene residues, of between 60 and 500, for example, in accordance with the process described herein, may take between 10 at 12 hours, where the polymerization reaction temperature is brought to a temperature where the

INSTITUTO MEXICANO V'A —'- Ή DE LA PROPIEDAD industrial values ti/2 Temperature dependent (or photo dependent) of an unactivated reducing agent to decompose to form an activated reducing agent can be between 3 0 sec. and 30 min The temperature for the process may comprise a temperature of 10 ° C below the boiling point of the unsaturated monomer, such as 15 ° C, 20 ° C, 25 ° C below the boiling point of the unsaturated monomer. The process temperature may comprise a temperature where the polymerization rate can be accelerated by at least 10%, for example, 15%, 20%, 30%, 50%, 75%, or 100%.

The preparation of a polymer comprising a degree of polymerization of, for example, comprising acrylate residues, of between 15 and 5,000, for example, in accordance with the process described herein is brought to a temperature where the values ti /2 Temperature dependent (or photo dependent) of an unactivated reducing agent to decompose to form an activated reducing agent can be between 30 sec. and 30 min. Similarly, preparing a polymer comprising a degree of polymerization of, for example, comprising acrylate residues, of between 60 and 500, for example, in accordance with the process described herein, may take between 3 at 5 hours, where the

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polymerization reaction temperature is brought to a temperature where the values ti /2 Temperature dependent (or photo dependent) of an unactivated reducing agent to decompose to form an activated reducing agent can be between 30 sec. and 30 min. The temperature for the process may comprise a temperature of 10 ° C below the boiling point of the unsaturated monomer, such as 15 ° C, 20 ° C, 25 ° C below the boiling point of the unsaturated monomer. The process temperature may comprise a temperature where the polymerization rate can be accelerated by at least 10%, for example, 15%, 20%, 30%, 50%, 75%, or 100%.

Suitable methods for preparing a polymer from unsaturated monomers that may be useful in the reactions and / or formation of (co) polymers, in the various embodiments presented and described in this application, may comprise forming a polymer having a degree of polymerization of 200 or less over a polymerization reaction time of 12 hours or less. For example, the prepared polymer can have a degree of polymerization of between 10 and 200, such as between 10 and 175; between 10 and 150; between 10 and 125; between 10 and 100; between 10 and 75; between 10 and 50; between 25 and 200; between 50 and

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200; between 75 and 200; between 100 and 200; between 125 and 200; between 150 and 200; between 175 and 200; or combinations thereof, which can be prepared over a polymerization reaction time of between 2 hours and 12 hours, such as between 3 and 10 hours; between 4 and 9 hours; between 5 and 8 hours; between 6 and 10 hours; between 6 and 8 hours; between 2 and 7 hours; between 3 and 10 hours; or combinations thereof.

Suitable polymers formed by the method described in

<td colspan="2">present they can</td><td>be useful in</td><td>the</td><td colspan="2">reactions and / or</td>

<td>training</td><td>of the</td><td>(co) polymers,</td><td>in</td><td>the</td><td>diverse</td>

<td>modalities</td><td colspan="2">presented and described</td><td>in</td><td>this</td><td>request,</td>

they may have a polydispersity index (POI) less than 15 2.5, for example, a POI less than 2.0, such as less than 1.7. For example, a polymer formed by the methods described herein can have a PDI of between 1.0 to 2.5, such as between 1.0 and 2.3; between 1.0 and 2.0; between

1.0 and 1.9; between 1.0 and 1.8; between 1.0 and 1.7; between 1.0 and 20 1.6; between 1.0 and 1.5; between 1.0 and 1.4; between 1.0 and 1.3;

between 1.0 and 1.2; between 1.0 and 1.1; between 1.05 and 1.75;

between 1.1 and 1.7; between 1.15 and 1.65; or between 1.15 and 1.55.

In operation, the addition of the reducing agent not activated in certain modalities, beyond the amount

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Initial proportion provided to the polymerization system can be influenced by a number of factors, such as the desire to allow dispersion or substantial dispersion of the non-reducing agent in the polymerization system before it generates the activated reducing agent. For example, it is necessary to consider the temperature of the polymerization reaction to which an unactivated reducing agent is added, such as a thermo-activated reducing agent, such as AIBN, since this is related to the conversion rate, such as speed ti /2 thermal decomposition, to form the activated reducing agent.

For example, in an effort to provide even, or even substantially, dispersion of the unactivated reducing agent prior to conversion to an activated reducing agent, it is necessary to consider factors such as the rate of addition of the unactivated reducing agent, or the amount of the non-activated reducing agent that is added, or both, and can be influenced by this relationship between the reaction temperature and the conversion rate to form the activated reducing agent. For example, if the conversion rate of the unactivated reducing agent at a particular reaction temperature is shorter than the time it takes to disperse

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uniformly (or almost uniformly) the agent in the system, then there is the potential for localized exotherms or hot spots to occur, which can be a safety hazard, but also an impact on the molecular weights and PDI of the polymer products formed due to the high or very high concentrations of radicals in these localized regions. If the conversion rate of the unactivated reducing agent at a particular reaction temperature is much greater than the time it takes to uniformly (or almost uniformly) disperse the agent into the system, then the efficiency of the polymerization reaction process may decrease , unnecessarily extending the total reaction time. It can also result in the accumulation of larger amounts of the reducing agent in the polymerization mixture which can be a safety hazard. In view of these concerns, the rate of addition of the unactivated reducing agent can be continuous, periodic, or intermittent, adjustable, or combinations thereof, to achieve a regular dispersion or practically regular dispersion of the unactivated reducing agent before it generates an agent. activated reducer that subsequently activates an inactive metal halide catalyst to drive the polymerization reaction.

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In certain embodiments, the particular relationship between reaction temperature and conversion rate, such as rate ti / 2 of thermal decomposition, to form an activated reducing agent from an unactivated reducing agent, may provide the ability to initiate or stop (start-stop) the polymerization reaction in a safe, effective and convenient way. For example, the progress, degree, and / or rate of the polymerization reaction can be regulated or controlled by the rate of addition and / or the amount of the unactivated reducing agent added. For example, the progress, degree and / or speed of the polymerization reaction can be stopped by stopping the addition of the unactivated reducing agent can allow the reaction to stop in a relatively short period of time (such as between 3-30 min). Similarly, the progress, degree and / or speed of the polymerization reaction can be started by starting the addition of the unactivated reducing agent can allow the reaction to start in a relatively short period of time (such as between 3-30 min, for example, within the conversion rate of you /2 at the reaction temperature). In certain embodiments the polymerization reaction can undergo a series of start-stop cycles during the production of a product

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polymer in particular. Reasons for wanting to have this ability to start-stop the polymerization reaction, especially on an industrial scale, may include, but are not limited to, safety issues, certain product quality, such as regulating the molecular weights of products or the degree of polymerization; convenience issues, such as a change in staff shifts; altering reagent feeds, such as altering the monomer feed, eg, changing the monomer identity to produce a copolymer or to add a crosslinker to form a star-shaped macromolecular polymer; and / or combinations thereof.

For example, the determination of when to perform a start-stop process in relation to the addition of the unactivated reducing agent may be based on the molar% conversion that has been achieved by a polymerization reaction process, converting an unsaturated monomer into the form of a polymer or polymer component. The molar% conversion that can signal the start, stop, or adjust rate of addition of a portion, or additional portion, or an unactivated reducing agent may include, but is not limited to, at least

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10 mol% conversion, relative to the initial molar amount of unsaturated monomer introduced into the polymerization system, eg, 40 mol% conversion, such as at least 2 0 mol%; at least 25 mol%; at least 30 mole%; or at least 35 mol% conversion, relative to the initial molar amount of unsaturated monomer introduced into the polymerization system.

In certain embodiments, polymers prepared in accordance with the process described herein can be used in the formation of polymer compositions comprising star-shaped macromolecules. For example, the star-shaped macromolecule may have a center and five or more polymeric arms. The number of arms within a prepared star-shaped macromolecule can be covalently attached to the core of the star. The arms of a prepared star-shaped macromolecule can comprise one or more polymeric segments or co-polymeric segments (such as block copolymers), and at least one arm and / or at least one segment can show a different solubility than at least another arm or another segment, respectively, in a reference liquid of interest.

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The prepared star-shaped macromolecule may be a mikto star-shaped macromolecule.

In certain embodiments, polymers prepared in accordance with the processes described herein can be used to prepare a star-shaped macromolecule, containing: a plurality of arms containing at least two types of arms, wherein the degree of polymerization of a first type of arm is greater than the degree of polymerization of a second type of arm, and wherein the first type of arm has a distal end portion that is hydrophobic. The star-shaped macromolecule can be formed by first forming or obtaining the hydrophobic portion and then forming the remaining portion of the first type of arm from the end of the hydrophobic portion and the second type of arm in a synthesis in a container, wherein the polymerization of the second portion of the first type of arm begins before the initialization of the second type of arm, but there is at least some point where the portions, for example, Substantial portions of the first type of arm and the second type of arm extend polymerically simultaneously.

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In certain embodiments, polymers prepared in accordance with the processes described herein can be used to prepare a composition of star-shaped macromolecules, where the number of arms on any particular star-shaped macromolecule can vary throughout the population of star-shaped macromolecules of each composition, due to the synthetic process used for the synthesis of the composition. This process is called the first arm method.

Suitable star-shaped macromolecules that can be formed at least in part by the reactions and / or (co) polymers, in the various embodiments presented and described in this application, can include those having a wide range of total number of arms, for For example, a star-shaped macromolecule can comprise a number greater than 15 arms. For example, a suitable star-shaped macromolecule can comprise between 15 and 100 arms, such as between 15 and 90 arms; between 15 and 80 arms; between 15 and 70 arms; between 15 and 60 arms; between 15 and 50 arms; between 2 0 and 50 arms; between 25 and 45 arms; between 25 and 35 arms; between 30 and 45 arms; or between 30 and 50 arms.

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Abbreviations used in the following examples

ATRP Radical Atomic Transfer Polymerization ARGET Electron Transfer Regenerated Activators

ICAR Initiators for continuous regeneration of the activator

DEBMM diethyl 2-bromo-2-methylmalonate

BrPN 2-bromopropionitrile

TPMA tris (2-pyridylmethyl) amino

AIBN 2,2'-azobis (2-methylpropionitrile

V-70 2,2'-azobis (4-methoxy-2.4-dimethyl valeronitrile)

Examples and discussion of examples

During the first attempts to scale ARGET / ICAR ATRP detailed below, it became apparent that the number of variables that have to be controlled was significantly greater than initially expected as the scale of the reactions increased. Therefore, in order to define optimal polymerization conditions for the new ICAR ATRP feed methods, it was crucial to generate a set of parameters for the radical initiator feed rate that took into account the type

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specific for monomer, reaction temperature, type of radical initiator, concentrations and proportions of all reagents, etc. Kinetic modeling was carried out to select the initial conditions to achieve synthetic objectives and to understand the factors affecting the control under several different conditions. In addition, some additional parameters were taken into account such as the diffusion rate of the initiator fed into the solution, the heat transfer in relation to the design of the reactor, the viscosity of the polymer solution in a known conversion, and others.

Potential starting points were investigated by computer modeling of critical process factors by conducting 1 L scale experiments with a single source of added reducing agent. All of these factors were carefully studied to achieve good control over the polymerization process to provide the kinetic data required to scale further to industrial scale equipment.

Computer simulations

The synthetic conditions of the new feeding method for ICAR were modeled by computer

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ATRP. Affordable software was successfully applied to many polymerization systems including the normal and ICAR ATRP [Macromolecules 2007, 40, 6464-6472.] And allows accurate calculation of the concentration of all species (including intermediates) in a reaction against time or conversion. It also allows estimating the molecular weight distributions of all polymeric species. All the required parameters such as constants, initial concentrations of all reagents and the rate of radical indicator feeding are entered in the software workshop assistant. Computer simulations are simple to perform and can be completed in a short period of time, so a wide number of different variables can be studied to optimize the new feeding method for an example ICAR ATRP. Common variations for specific monomers are discussed below. At ICAR it is crucial to correlate radical initiator feed / generation rate (IR) with other parameters (temperature, type of radical initiator, etc.) in order to obtain good control over the polymerization process.

Computer simulations for the polymerization of methyl methacrylate

Figure 2 shows the initial set of parameters used for the computer simulations carried out for the polymerization of MMA with continuous feeding of two different radical initiators at a series of temperatures, targeting different DPs. Preliminary results from the initial simulation of the proposed method suggested that this approach is possible to process condition assessment.

The overall ratio of reagents from a non-limiting example of the new ICAR ATRP feed method with 50 ppm Cu amount was: M / RX / CuBr2 / ligand / RI = X / 1 / 0.01 / 0.01 / 0.05 in bulk at a temperature T (where M- monomer, RX -alkyl halide initiator, RI - radical initiator, X = 100, 500). Commercially available tris (2-pyridylmethyl) amino (TPMA) was used as the exemplary starting ligand, and diethyl 2-bromo-2-methylmalonate (DEBMM) was used as an exemplary alkyl halide initiator in polymerization systems. Other catalysts and initiators were also evaluated. RI was fed to the reaction medium at two different rates and the target reaction time was set to either 6 or hours.

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Therefore, the initial set of MMA polymerization simulations using the new feeding method was carried out with an amount of 50 ppm Cu and the ratio of the reagents: MMA / DEBMM / CuITEMBr2 / TPMA / RI = X / 1 / 0.01 / 0.01 / 0.05 in bulk. Two different radical initiators were used, 2.21-azobis (2-methylpropionitrile) (AIBN), with a decomposition temperature, at a half-life of 10 hours, of 65 ° C) and 2.21-Azobis (4-methoxy-2,4-dimethyl valeronitrile) (V-70), with a decomposition temperature, at a half-life of 10 hours, of 30 ° C). Different temperatures were applied for polymerization with AIBN (70, 80, 90 ° C) and V-70 (45, 55, 70 ° C) as a radical initiator. These provide decomposition half-life times of 300, 70, 20 minutes, and 60, 15, 3 minutes, respectively. Two different degrees of polymerization (DP = X = 100, 1000) will be chosen in order to cover a typical range of molecular weights accessible with the new method. The radical starter feed rate will be set for 6 and 24 hours as an end time.

The total volume of the radical initiator solution fed for the reaction was less than 10% against the monomer volume (reaction volume),

that is, while diluting the initiator solutions were added, the total of the added solvent will be within the limits associated with the removal of the monomer from a bulk polymerization. The ultimate goal was to provide conditions for the polymerization of a range of methacrylate monomers.

It is expected that a wide range of Type I and Type II photoinitiators can be employed and the simulations will examine the effects of the speed / intensity of the simulation.

Other simulations designed to provide starting conditions for the examined polymerization reactions of periodic addition / formation of radical initiators or reducing agents for transition metal complexes, studied a range of parameters include:

The type of monomer (different propagation and termination rate constants will be applied, as well as activation and deactivation to different types of monomers and catalysts). The initial three exemplary monomers were styrene, n-butyl acrylate, and methyl methacrylate, as they cover the three

main classes of radical polymerizable monomers.

The type of radical initiator (different constants of decomposition speed, also depending on temperature).

The type of catalyst (different activation and deactivation rate constants).

The degree of polymerization (DP) (low and high MW).

Temperature (change in initiator decay rates by radicals and all other rate constants)

The speed and method of feeding for the radical initiator / activator (slow, fast and periodic).

Other parameters such as the proportions and concentrations of the reagents were initially kept constant, but later they also varied with the objective of minimizing the amount of copper and of the initiator, and optimizing the polymerization rate.

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IN & UjTRiAi.

Figure 3 shows the simulated kinetic graph, the molecular weight and polydispersity (PDI) against conversion and the trace of the PMMA GPC prepared by the feeding method for ICAR ATRP. The results shown in Figure 3 are for simulations made for experimental conditions: MMA / DEBMM / CuITEMBr2 / TPMA / AIBN = 500/1 / 0.02 5 / 0.025 / 0.05 in bulk at 90 ° C, with a constant concentration of the added initiator over a feeding time of 10 h. linear kinetics, good control over molecular weight, lower PDI and monomodal molecular weight distribution show that polymerization can be well controlled.

A series of simulations was performed using methyl methacrylate, butyl acrylate, and styrene as exemplary monomers. The results of the initial series of simulations of these three monomers provided starting points for the reactions performed in an IL reactor. Based on the experimental results, some additional simulation changes can be made to fully optimize the investigated polymerization system.

A similar series of simulations will be conducted using a light responsive initiator to determine if the

100 Radical formation speed can be controlled by controlled photo-simulation.

A similar series of simulations will be performed using a reducing agent to determine if ARGET ATRP can be performed under depleted feeding conditions and results in improved control.

Polymerization Experiments

Polymerization experiments were performed using the new ICAR ATRP feed method for three representative monomers (MMA, nBA, and St) on a 1-liter scale in an Ace Glass reactor equipped with a heating mantle, mechanical stirrer, and thermocouple. On this reaction scale, changes related to heat transfer and viscosity, as well as exothermicity, became important; as discussed in the background section and as shown in Figure 1. These factors are not taken into account by computer modeling software. Thus, some adjustments were made in order to fully optimize the new feeding method in the actual ICAR ATRP experimental examples.

101

However, each monomer was initially polymerized with the conditions initially optimized by computer simulations. Additional adjustments were made in order to increase additional control over polymerization. These settings are specified for each of the following monomers.

The run or run numbers listed below were used for internal monitoring of the experiments and have no additional meaning.

Comparative example Cl:

ARGET ATRP of MMA with Sn (EH) 2 as reducing agent: Execution 07-004-83. Scale: in a 1L reactor.

Conditions: MMA / DEBMM / CuBr2 / TPMA / Sn (EH)2 = 2200/1 / 0.015 / 0.06 / 0.1 in DMF (0.05 eq. Volume against MMA), (7 ppm Cu), T = 65 ° C

Polymerization was carried out in bulk and at 65 ° C. The reaction was well controlled with Mn close to the theoretical values and lower PDI. Reaction kinetics and CPG results of polymer samples taken

102

during the experiment they are shown in Figure 4. After 27.6 hours the final degree of polymerization (DP) of the polymer was 890 and the Mn (GpC)= 90,000 with a polydispersity of 1.17. A small low molecular weight Coleus is visible on the GPC traces.

Comparative Example C2:

Chain extension of the polymer prepared in example Cl: Execution 07-004-84. Scale: 25 mL Schlenk flask.

Conditions: St / PMMA / CuBr2 / TPMA / Sn (EH)2 = 5000/1 / 0.02 / 0.06 / 0.2 in anisole (0.1 eq. Volume against

St), (4 ppm Cu) T = 80 ° C. (07-004-83 as macroinitiator)

The kinetics of the reaction and the GPC results of the experiment are shown in Figure 5.

The GPC results of the polymer samples taken during the experiment indicate that the chain extension of the PMMA macroinitiator formed in Example Cl with St was not entirely successful. One can conclude that despite a narrow POI of

103

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macroinitiator, the chain termination functionality is not very high, after a 4,000 minute reaction some macroinitiators had not yet extended the chain, resulting in a bimodal molecular weight distribution.

One reason for low chain termination functionality is a transfer reaction of the increasing radical to Sn (EH)2 indicating that a different reducing agent has to be used in order to synthesize PMMA with higher molecular weight and higher chain termination functionality.

Comparative Example C3:

ICAR MMA ATRP with AIBN as radical initiator. Execution: 07-004-85. Scale: 1L reactor

Conditions: MMA / DEBMM / CuBr2 / TPMA / AIBN = 2400/1 / 0.02 / 0.025 / 0.15 in anisole (0.03 eq. Volume against MMA), (8 ppm Cu), T = 55 ° C.

The kinetics of the reaction and the GPC results of the polymer samples taken during the experiment are shown in Figure 6. In this comparison example

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INSTJ i UTO E. '/ ÍCZ, Γ.Ό DC INDUSTRIAL property

Bulk MMA polymerization was performed at 55 ° C in the presence of AIBN instead of Sn (EH)2 to prevent apparent Sn (EH) transfer reactions during the chain extension reaction described in Example C2. After a 45.5 hour reaction the DP of the polymer was 894 and the PM 89,500 with Mn close to theoretical values and lower PDI, indicating that the polymerization was well controlled. No glue is visible on the GPC traces suggesting that transfer reactions did not occur during the polymerization process.

Comparative Example C4:

The chain extension of the polymer prepared in the

<td>Example C3. 25 mL.</td><td>Execution:</td><td> 07-004-89.</td><td>Scale: flask</td><td>Schlenk</td>

<td>Terms:</td><td>St / PMMA</td><td>/ CuBr2 /</td><td>TPMA / Sn (EH)2 =</td><td> 5000 /</td>

<td> 1 / 0.02 /</td><td> 0.06 / 0.2</td><td>in anisole</td><td>(0.1 eq. Volume</td><td>against</td>

St), (4 ppm Cu), T - 80 ° C, time = 40.2 hr. Shows

C3, 07-004-85 as macroinitiator

The kinetics of the reaction and the GPC results of the polymer samples during the experiment are shown

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in Figure 7. The extension of the PMMA C3 chain with St was successful. The chain termination functionality of PMMA C3 is much higher than that of PMMA Cl, no bimodal molecular weight distribution was observed after extension, only a small coleus is visible in the GPC traces of the polymer samples during the experiment . This result proves that one reason for low PMMA Cl chain termination functionality is the transfer reaction to Sn (EH) 2. Indicating that an ICAR ATRP or a reducing agent based on non-metal transition has to be used in order to obtain PMMA with greater chain termination functionality.

Comparative Example C5:

ICAR MMA ATRP with AIBN as radical initiator. Execution: 08-006-48. Scale: in a 1L reactor.

Conditions: MMA / DEBMM / CuBr2 / TPMA / AIBN = 2400/1 / 0.025 / 0.03 / 0.2 in bulk (anisole as internal standard), (10 ppm Cu), T = 55 ° C, time = 41.6 hours.

The reaction kinetics and GPC curves of the polymer samples taken during the experiment are

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shown in Figure 8 indicating that the final polymer has a DP of 1414 and Mn (CPG) 141,600. Polymerization was well controlled at baseline. The final POI of sample 3 was slightly higher than that of sample 2, but significant fluctuations in temperature were found when the larger conversion was attempted indicating that the flask had been heated for a long time, resulting in a polymerization without control. This is a consequence of a high viscosity of the glassy polymer solution at low temperatures. Although a high molecular weight was reached, the chain termination functionality may be lower due to overheating of the polymerization solution resulting in a glassy solid polymer and a broken stir bar.

Example 1. Polymerization of Methyl Methacrylate (MMA)

MMA polymerization was performed using first the new feeding method for ICAR ATRP. The best polymerization conditions were chosen from a computer modeling and tested on a 1-liter reactor scale. The temperature inside the reactor was followed using a thermoelectric pair located outside the reactor, between the reactor wall and the

107

heating to provide additional information on the level of temperature control obtained in the reaction. The difference in temperature between the two thermoelectric pairs can be related to the efficiency of heat transfer in this system. Heat transfer efficiency can change significantly with viscosity and will affect polymerization control.

Another factor that computer modeling does not take into account is the rate of diffusion of the initiator by radicals after feeding in a viscous solution. The radical initiator must be evenly distributed before significant decomposition occurs. With the purpose of investigating that, at different stages of polymerization (when the solution will become increasingly viscous), a color dye will be injected and a time of its distribution will be evaluated (visually and / or spectroscopically). The results of this study will provide information on the distribution of injection sites that are required for optimal control in a large-scale reactor.

MMA polymerization using the proposed method

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The results of the computer simulations were used as starting points for 10 test reactions. It was determined that an excess of ligand has to be used in order to obtain a controlled polymerization. Polymerizations revealed that linear kinetics and molecular weights were close to theoretical values. However, when a PD was determined as a target under the PDI remnants they remained quite large, Figure 9. Additional reactions were then performed to optimize PMMA synthesis using the described feeding method. The results and observations during the initial experiments indicated that the reason for the bad results, broad PDI, is a very low DEBMM initiation efficiency in the ICAR ATRP system, a signal was visible from the initiator in GC traces even after many hours reaction. For polymers with higher DP the molecular weights were lower than the theoretical values, and PDI initially decreased with the conversion but increased to a higher conversion, Figure

10. Another observation was that the polymerization mixture was becoming cloudy with the reaction time. This is probably the reason for the loss of control at the end of most of the polymerization reaction. Selected ATRP initiator (DEBMM) determined

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was primarily responsible for the side reaction and destabilization of the very low concentration of the copper catalyst.

Therefore, a more efficient primer, BrPN, was tested in ICAR ATRP with AIBN feed and good results were obtained.

After performing the first reactions with MMA, the experimental and simulated results were compared. The differences can be attributed to the effects of heat transfer, viscosity, initiator diffusion, impurities, and the amount of air in the system. These observations indicate that the reactor should be equipped with a mechanical stirrer. In order to further reduce problems related to diffusion and heat transfer, reactions can be diluted (with monomer or solvent) and stopped at minor conversions (unreacted monomers (diluents) can be recovered and reused). Additional experiments were carried out with the aim of optimizing the reaction conditions on this scale with a single source of added initiator. Parameters that were adjusted include: temperature, target DP, radical initiator feed rate,

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reagent concentration and catalyst amount of

Cu.

Example 2. Polymerization of n-butyl acrylate

Computer simulations of the polymerization of n-butyl acrylate

A computer model similar to the one shown in Figure 2 was constructed and then polymerization simulations for n-butyl acrylate (nBA) were performed. The main objective of the simulations was to find starting conditions for real polymerization experiments by varying different parameters in the software, type of radical initiator, degree of DP polymerization, radical initiator feed rate.

One of the goals of the new initiator / activator controlled feed polymerization method was to make polymerization reactions as fast as possible while still having a controlled process. As in the case of PMMA, the evaluation of simulated results for VnBA was based on these factors and a new evaluation scale was introduced.

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111

The scale was slightly different than that for MMA due to the relatively faster reactions for the nBA type monomer.

Description of the scale for relative control

Very good: conversion> 99% after less than 6 hours of reaction and a PDI <1.15 and functionality> 98%, with linear kinetics.

Good: conversion = 95-99% after less than 10 hours of reaction or PDI = 1.15 -1.20 or functionality = 95-98%,

Intermediate: conversion = 80-95% after less than 20 hours PDI = 1.20-1.25 or functionality = 85-95%,

Poor: conversion <80% after less than 20 hours or POI> 1.25 or functionality <85%.

All rates and rate constants were adjusted for each simulated polymerization as reported in Table 1 below.

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Industrial

Table 1.

<td>Kxp.</td><td>Control relative</td><td>Conv. I% l</td><td>Weather IN</td><td>KOI</td><td>Pune. Item</td><td>Comments</td>

<td>Ή</td><td>Good</td><td> 99.2</td><td> 1.7</td><td>l. 1.2</td><td> 99</td><td>An induction period was observed</td>

<td>25a</td><td>Deficient</td><td> 99.2</td><td> 0.5</td><td>i .38</td><td> 99</td><td>Major POI</td>

<td>25b</td><td>Very good</td><td> 99.2</td><td> 1.2</td><td>LI?</td><td> 99</td><td>A very short induction period was observed</td>

<td>2b</td><td>Good</td><td> 99.2</td><td> 3.3</td><td> 1.14</td><td> 99</td><td>An induction period was observed</td>

<td>-Ί7</td><td>Good</td><td> 99.2</td><td> 2.6</td><td> 1.12</td><td> .99</td><td>An induction period was observed</td>

<td> 28</td><td>Good</td><td> 99.2</td><td> 4.8</td><td> 1.09</td><td> 99</td><td>An induction period was observed</td>

<td> 29</td><td>Good</td><td> 99.2</td><td> 4.3</td><td> 1.1!</td><td> 99</td><td>An induction period was observed</td>

<td> 30</td><td>Intermediate</td><td> 99.2</td><td> 7,5</td><td> 1.08</td><td> 99</td><td>An induction period was observed</td>

<td> 31</td><td>Good</td><td> 99.2</td><td> 4.5</td><td> 1.07</td><td> 99</td><td>An induction period was observed</td>

<td>31a</td><td>Deficient</td><td> 99.2</td><td> 0.9</td><td>i .38</td><td> 97</td><td>Major POI</td>

<td> 32</td><td>Intermediate</td><td> 99.2</td><td> ¡1.3</td><td> 1.04</td><td> 99</td><td>An induction period was observed</td>

<td>32b</td><td>Intermediate</td><td>i 99.2</td><td> 1.4</td><td> 1.21</td><td> 98</td><td>Average POI</td>

<td> 33</td><td>Good</td><td> 99.2</td><td> 6.0</td><td> 1.07</td><td> 99</td><td>An induction period was observed</td>

<td> 34</td><td>Intermediate</td><td> 99.2</td><td> 13,4</td><td> 1.04</td><td> 99</td><td>An induction period was observed</td>

<td> 35</td><td>Deficient</td><td> 45.5</td><td> 6.0</td><td> 1.09</td><td> 99</td><td>Slow reaction</td>

<td> 36</td><td>Intermediate</td><td> 99.2</td><td> 18.6</td><td> 1.04</td><td> 99</td><td>An induction period was observed</td>

<td> 3</td><td>Good</td><td>i 99.2</td><td> 1.9</td><td>Mess</td><td> 99</td><td>An induction period was observed</td>

<td> 38</td><td>Good</td><td> 99.2</td><td> 4.1</td><td> 1.10</td><td> 99</td><td>An induction period was observed</td>

<td> 39</td><td>Good</td><td> ' 99.2</td><td> 2.9</td><td> 1,18</td><td> 99</td><td>An induction period was observed</td>

<td> 40</td><td>Good</td><td> : 99.2</td><td>? i</td><td> 1.11</td><td> 99</td><td>An induction period was observed</td>

<td> 41</td><td>Good</td><td> 99.2</td><td> 4.2</td><td> 1.19</td><td> 99</td><td>An induction period was observed</td>

<td> 42</td><td>Good</td><td> 99.2</td><td> 7.8</td><td> 1.12</td><td> 99</td><td>An induction period was observed</td>

<td> 43</td><td>Good</td><td> 99.2</td><td> 4.9</td><td> 1.09</td><td> 99</td><td>An induction period was observed</td>

<td> 44</td><td>Intermediate</td><td>i 99.2</td><td> 12.8</td><td> 1.04</td><td> 99</td><td>An induction period was observed</td>

<td> 45</td><td>Good</td><td> 99.0</td><td> 6.0</td><td> 1.11</td><td> 98</td><td>An induction period was observed</td>

<td> 46</td><td>Intermediate</td><td> 99.2</td><td> 14.9</td><td> 1.05</td><td> 99</td><td>An induction period was observed</td>

<td> 47</td><td>Good</td><td> 92.4</td><td> 6.0</td><td> 1,12</td><td> 99</td><td>An induction period was observed</td>

<td> 48</td><td>Intermediate</td><td> 99.2</td><td> ! 7,8</td><td> 1.06</td><td> 99</td><td>An induction period was observed</td>

113

In almost all cases the resulting polymers have a lower PDI, higher chain termination functionality and molecular weights close to theoretical values. High polymerization rates were observed in most reactions (even for higher DP) and that is why most simulations are rated here as good since nonlinear kinetics were observed. In

<td>conclusion</td><td>the</td><td>simulations</td><td>for</td><td>the</td><td>polymerization</td><td>of</td><td>nBA</td>

<td>using</td><td>the</td><td colspan="2">New method</td><td>of</td><td>feeding</td><td colspan="2">were</td>

<td>successful and</td><td>I know</td><td>They found</td><td>the</td><td colspan="3">optimal conditions;</td><td>by</td>

example Simulations 25, 25a, (see Figure 11) 2629, 31, 33, 37-43, 45, 47. In general, there was no significant difference in terms of control over polymerization when using a lower or higher T , different radical initiator or different feed rate. As expected, reactions were faster with V-70, with higher T or faster feed rate. The positive effect of radical initiator feeding for acrylates is much greater than for MMA or St discussed later. When no feed is applied (simulation 25a), polymerization is not controlled for nBA (higher PDI), Figure 1.

Optimized conditions using computer software simulations were used in the

114 1L scale experiments. The results obtained during these experiments for nBA are reported below.

Example 2A. Preparation of PnBA by ICAR ATRP depleted feed

Four of the best modeling stage polymerization conditions were chosen and first tested in a 1 liter scale reactor. The experimental setup had a difference compared to the MMA system; The reactor was equipped with a cooling coil, necessary for safety reasons - since reactions with acrylates are more exothermic. As discussed in the background, we anticipate far less exothermic effects for the depleted feeding method. The parameters that were adjusted are: temperature, target DP, radical initiator feed rate, reagent concentration and amount of Cu catalyst.

Execution: 08-006-57

Scale: 1 L reactor i reactor.

Γ 'ίΤυΤΌ ΜΞΖΤΤΛΝΟ

I3 THE FROFJfDAD

INDUSTRIAL

115

Conditions: η I DEBMM / CuBr2 / TPMA / AIBN = 2000/1 /

0.02 / 0.04 / 0.04 in bulk (anisole as internal standard), (10 ppm Cu), T = 90 ° C, time = 7.5 hours.

The rate of addition of the AIBN solution of AIBN 34.5 mg in 15 ml of toluene was 2ml / h, which is equivalent to adding 0.01 eq. AIBN / h compared to the amount of the added ATRP initiator. The initial volume of liquid in the reactor was 840 mL. After 3 hours and 10 minutes of an exothermic reaction it was noted in the temperature profile and the addition of AIBN was stopped and the cooling water was started. Cooling continued for one minute and then stopped. The reaction temperature slowly returned to 90 ° C and the addition of the AIBN solution was resumed after 4 hours at a reduced rate of 1 ml / h and no further exothermic reaction was observed. The reaction stopped after 71Within hours.

The kinetics of the reaction and the GPC results of the experiment are shown in Figure 12 indicating that the final polymer has a DP of 7 00 and an Mn (Gpc) 89,900 with a final POI of 1.26.

The most critical observation was that the polymerization temperature was well controlled and in contrast to the

116

results shown in Figure 1 this reaction was not excessively exothermic as a consequence of the minor absolute amount of AIBN added over the initial period of 3 hours and when the instantaneous concentration of the initiator exceeded the concentration of the CuBr catalyst2 / TPMA formed due to termination reactions the resulting exotherm could be easily controlled by stopping the addition of the initiator. The slow rate of completion at a higher conversion resulting from the increased viscosity required a slower rate of addition of AIBN.

Therefore in this example, the concept of starter depleted feed was determined to provide improved control.

Example 2B. NBA polymerization

The polymerization conditions of simulation 37 were taken as the starting point for execution 08-006-194 with V-70 feeding at 7 0 ° C. The polymerization was very slow at the beginning (induction period) and after 2 h the polymerization ratez increased significantly. The conversion reached 96% after only 4 hours of reaction. This quick process of

117

MPT

polymerization was not well controlled. Although the molecular weights were close to the theoretical values, the PDI was high (> 1.7) and did not decrease with the conversion. The induction was also clearly visible in each simulation. These results suggested that a significant amount of the initiator has to be consumed before there is an increase in the rate of polymerization. Therefore, in the 08-006-195 nBA run, a higher monomer to initiator ratio was employed (DP = 1000). It can be seen from Figure 13 that the control over polymerization was significantly improved. As in the previous case, the kinetic graph was not linear but the molecular weights were close to the theoretical values. The GPC traces were modomodal and changed with the reaction time. The molecular weight distribution of the synthesized polymer decreased during the polymerization of PDI = 1.78 to 1.31. The induction period was around 5 h and after this time a strong exothermic effect was observed as shown in Figure 14. The temperature increased from 7 0 ° C to 110 ° C. The exothermic effect was controlled by stopping the addition of V-70 to the reaction mixture. After stopping the addition, polymerization as well as any temperature increases within the reactor were stopped.

118

ÍMPI 'NS'NTLTO Míxirjrio DE LA WOPiSOAD INOUSTiUAL

This experiment shows that the feeding method is safe for the exothermic reaction of polymerizations. Control of the exothermic effect can be of great importance in terms of safety as well as control over the molecular weight, PDI and functionality of the final polymeric material.

Additional examples for the nBA polymerization were also targeted at a higher DP and a small amount of V-70 was added at the start of the polymerization process to reduce the induction period. Low DP nBA polymerization was also repeated with a larger amount of copper catalyst. In both reactions, well-controlled polymerization was observed.

Example 3. Polymerization of Styrene (St)

Styrene polymerization was performed by the new feeding method for ICAR ATRP using the same strategy as for the MMA monomer. Four of the best polymerization conditions were chosen from the computer modeling step and tested in a 1-liter scale reactor. After the preliminary, detailed results

119

IMPI

MEXICAN INSTITUTE From INDUSTRIAL RROFLSDAO in Table 2, additional experiments were obtained that were performed under better conditions.

The parameters that were adjusted are: temperature, target DP 5, radical initiator feed rate, reagent concentration, and amount of Cu catalyst.

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The polymerization kinetics was followed by measurement of the rate of disappearance of the monomer by gas chromatography (GC) and / or by nuclear magnetic resonance (NMR). The synthesized polymers will be characterized by gel permeation chromatography (GPC). Successful polymerization of the M monomer should result in a P (M) polymer with monomodal and narrow molecular weight distribution (PDI <1.4). The molecular weight of the synthesized polymers should be close to the theoretical values as predicted from equation 2.

Mn, theo - ([Μ] 0/ [RX] o) X COnver S ΐθη XMmOnumber · (2)

Examples for Styrene Polymerization using the proposed method

The computer model was built and then polymerization simulations for styrene (St) were performed. Table 2 presents all the results for St polymerization using ICAR ATRP with AIBN feed. In experiment WJ-08-008-190 St was polymerized in the presence of DEBMM as an initiator with 50 ppm CuBr2 and excess TPMA. The

122

polymerization at 100 ° C and AIBN was fed at 0.004 eq. against DEBMM per hour. Polymerization reached 56% conversion in 10.5 h. Linear kinetics was observed and the molecular weights were very close to the theoretical values. In this experiment, PDI decreased during the reaction time from 1.35 to 1.16. In general, the process was completely controlled.

In the second reaction, WJ-08-006-192, Figure 15, a higher rate of addition of AIBN was applied in order to accelerate the rate of polymerization. Furthermore, a small amount of AIBN at t = 0 was added to the reaction mixture in order to reduce the majority of Cu (ll) to Cu (l) at the beginning of the polymerization step. Polymerization was almost twice as fast reaching 81% conversion in 9 hours. The kinetic graph has a linear dependence and the molecular weights were close to the theoretical values. The GPC traces were monomodal and changed with the reaction time. The molecular weight distribution of the synthesized polymers decreased during polymerization from 1.39 to 1.15. These data showed that the process was completely controlled.

123

1AVI. il i

MEXICAN INSTITUTE <I

OF THE PROPERTY " ''

INDUSTRIAL

In the final reaction reported in Table 2, reaction (WJ-08-006-193), St polymerization was performed by targeting a higher DPI. St was polymerized in the presence of DEBMM as an initiator with 50 ppm CuBr2 and excess TPMA. Polymerization was performed at 100 ° C and AIBN was fed at 0.008 eq. against DEB MM per hour. Figure 16 shows a kinetic graph for this reaction. After 9 h the addition of AIBN was stopped and the heating was turned off. It can be seen from Figure 16 that the polymerization process stopped immediately after stopping the initiator addition. The reactor was allowed to cool overnight (no cooling system was applied) and heated again after 21.6 hr to 110 ° C. At this time the AIBN feed was restarted with the same addition rate. It can be seen from the kinetics graph, Figure 17 and the molecular weights against the conversion graph Figure 16, that this reaction was restarted in a completely controlled manner.

Due to the higher temperature in the second phase of the reaction, the polymerization rate was higher. Figure 16 also shows the temperature inside as well as outside the reactor, thermocouples were placed inside the polymerization mixture and on the outside wall of the

IMPI

124 reactor. The temperature profile indicates good heat transfer, since the temperature difference of both thermocouples is similar and does not increase at any time during the reaction.

INSTÍTUTO Μ.ίΧ! Α ·; θ DS LA r '.' JíiF.DAÍ)

INDUSTRIAL

This dataset shows that the new feeding process can be fully automated and that ICAR ATRP with controlled feeding can be successfully applied in synthesis of PSt with higher and lower PDs.

Therefore, one embodiment of the invention describes how the rate of free radical initiator decay is a factor of the rate of CRP and the level of control over molecular weight, molecular weight distribution, and chain termination functionality. in the (co) polymer formed.

Another embodiment of the invention describes that if the temperature of the reaction medium moves above the target temperature and the addition of the initiator / reducing agent is terminated, there is no further exotherm and, once the temperature drops to the target temperature, The initiator / reducing agent feed can be started to restart the polymerization reaction.

Another modality of the described process is directed towards continuous control over the concentration of the persistent radical in an NMP. In this embodiment, the decomposition rate of the added initiator is selected to coincide with the rate of radical / radical termination reactions that could otherwise accumulate the concentration of the stable free radical and reduce the rate of propagation.

A further embodiment of the described process relates to RAFT polymerizations. In a RAFT polymerization the polymerization rate is controlled by the speed of the added initiator. Normally, all of the initiator is added to the reaction at the start of the reaction and this could lead to an increased rate of decomposition of the initiator if the temperature of the reaction is not well controlled throughout the polymerization vessel during each stage of the reaction.

In another embodiment of the invention, a photosensitive initiator is employed and the rate of radical generation is controlled by intermittent controlled photostimulation.

Although the preferred embodiments of the present invention have been shown and described herein, it will be

126 r; al

It is apparent to those skilled in the art that such embodiments are provided by way of example only. The following claims are intended to define the scope of the invention and that the methods and structures within the scope of these claims and their equivalents are covered thereby.

, NSTK / ·? mfxican

OF INDUSTRIAL PROPERTY

127

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12926780	United States of America	–	2010-12-08
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2011063673	United States of America	W	2011-12-07
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MX2012007079A	Mexico	A	2012-12-17
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Abstract

Term

PATENT TITLE NO. 338317

REQUEST

US

PRIORITY

THE DIVISIONAL DIRECTOR OF PATENTS

NAHANNY CANAL REYES

MX / 2016/28191

IMPROVED CONTROL OVER CONTROLLED PROCESSES OF

RADICAL POLYMERIZATION

IMPI

INSTITUTE N

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MEXICAN INSTITUTE

INDUSTRIAL

MEXICAN INSTITUTE OF PROPERTY

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MEXICAN INSTITUTE OF INDUSTRIAL PROPERTY

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MEXICAN INSTITUTE OF LA ROPIEDAD

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MEXICAN INSTITUTE OF INDUSTRIAL PROPERTY

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INDUSTRY

MEXICAN INSTITUTE OF PROPERTY

INDUSTRIAL

INDUSTRIAL

MEXICAN INSTITUTE OF INDUSTRIAL PROPERTY

MEXICAN INSTITUTE CE THE PROPERTY

INDUSTRIAL

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MEXICAN INSTITUTE OF PROPERTY

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