Process for the radical polymerization of thionolactides

Abstract

The present invention relates to a process for preparing copolymers, preferably degradable or biodegradable, from thionolactides. More particularly, the present invention relates to a process for preparing copolymers, preferably degradable, by radical ring-opening polymerization using in particular at least one thiolactide-type monomer, to the copolymers, preferably degradable, obtained by implementing this process, to the use of said thionolactide-type monomer as a precursor monomer in a radical polymerization, as well as to specific thionolactides. Figure for abstract: Fig. 1

Description

Title of the invention: Process for the radical polymerization of thionolactides

[0001] The present invention relates to a process for preparing copolymers, preferably degradable or biodegradable, from thionolactides.

[0002] More particularly, the present invention relates to a process for preparing copolymers, preferably degradable, by radical ring-opening polymerization using in particular at least one monomer of thionolactide type, to the copolymers, preferably degradable, obtained by implementing this process, to the use of said monomer of thionolactide type as precursor monomer in a radical polymerization, as well as to specific thionolactides.

[0003] The majority of synthetic polymers are currently synthesized by free-radical polymerization of vinyl monomers such as, for example, ethylene, methyl methacrylate, styrene, and vinyl acetate. Free-radical synthesis processes have the advantage of tolerating a wide range of functionalities, thus allowing the synthesis of many materials. The application of controlled free-radical polymerization techniques, developed towards the end of the 20th century, also allows the synthesis of polymers and copolymers of complex architecture, for example, block, gradient, or star copolymers, with control of the average molar mass of the polymer as well as the molar mass distribution.

[0004] One of the main disadvantages of polymers resulting from radical polymerization is that they are difficult to degrade. Indeed, the different monomer units are linked together by carbon-carbon (CC) bonds which are very resistant to degradation. This can lead to environmental damage and also limit the application of these polymers in the medical field where it is important to avoid the accumulation of high molar mass polymers in the body.

[0005] One way to introduce the property of degradability to synthetic polymers obtained by radical polymerization is to use a cyclic comonomer that polymerizes by radical ring-opening polymerization (RROP). These monomers are mainly of two types: vinyl and exo-methylene. When the cyclic comonomer of vinyl or exo-methylene type carries a degradable functionality, this can then be incorporated into the backbone of the polymer, making it itself degradable.

[0006] The polymerization of these monomers proceeds by the addition of a radical to a double bond, followed by the opening of the ring and the generation of a linear species according to the following reaction schemes (1) and (2), relating respectively to the vinyl and exo-methylene monomers:

[0007] [Chem.l] YZ RR YZ R ^YZ " rJ- VY Z^n / X -------- / / \ --------3»^ / S Reaction scheme (1)

[0008] [Chem.2] Y Z-- . R'?" Z " x YY V—y R" V—Rz V— Z' rE ii ■ ; Reaction scheme (2).

[0009] Among the vinyl-type monomers, we can cite vinyl cyclopropanes which were introduced in the 1960s. Among the exo-methylene-type monomers, we can cite ketene acetals introduced in the 1980s, including in particular 2-methylene-1,3-dioxane (MDO) which transforms into ester during radical polymerization [with Y = Y' = O in the reaction scheme (2)]. The MDO monomer has been studied in controlled radical polymerization, notably in Hedir et al., Biomacromolecules, 2015,16, 2049-2058. In general, ketene acetals copolymerize easily with vinyl esters and vinyl ethers but with more difficulty with styrenic monomers, (meth)acrylates and (meth)acrylamides. Furthermore, they are difficult to synthesize and are often obtained in fairly low yields. Other exo-methylene type monomers such as cyclic allylic sulfides (eg2-methyl-7-methylene-1,5-dithiacyclooctane) have also been described.

[0010] More recently, the use of a thionolactone, dibenzo[c,e]oxepane-5-thione (DOT) has been described in radical polymerization. Copolymers of this monomer with acrylonitrile, N,N-dimethyl acrylamide, poly(ethylene glycol)methyl ether acrylate (PEGA), methyl acrylate, and maleimides have been prepared. However, DOT is inert in the presence of methyl methacrylate, retards the radical polymerization of styrene without being incorporated into the polymer backbone, and inhibits the polymerizations of vinyl acetate and N-vinylpyrrolidone. In addition, its synthesis is complicated. Other thionolactones such as y-phenyl-y-butyrolactone and 4-thionophthalide, have been tested in copolymerization with different monomers and found to be inert [Bingham et al., Chem. Commun., 2019, 55, 55]. Finally, Ivanchenko et al. [Polymer Chemistry, 2021,12, 1931-1938] described the use of thionocaprolactone which was found to be inert towards n-butylacrylate.

[0011] Consequently, there is a need for synthetic processes that make it possible to access in a simple manner, preferably with good yields, new synthetic polymers having varied structures, and which are preferably degradable, or even biodegradable. There is also a need for precursor monomers that can react with comonomers of varied structures, for example both with activated comonomers such as styrenes or acrylates, and with non-activated comonomers such as vinyl esters.

[0012] Surprisingly, the inventors have developed a radical ring-opening polymerization process that makes it possible to achieve these goals, said process offering in particular a wide range of reactivity.

[0013] The present invention therefore has as its first subject a process for preparing at least one copolymer, preferably degradable, said process comprising at least one step of radical polymerization by ring opening of at least one cyclic monomer with at least one monomer comprising ethylenic unsaturation, in the presence of a radical polymerization initiator, said process being characterized in that:

[0014] (i) the cyclic monomer is chosen from the thionolactides of formula (I) below:

[0015] [Chem.3] S R1 R3 - O ? n4 i ■ RX œ in which: - X is an oxygen atom or a sulfur atom; - R1, R2, R3, and R4, independently of one another, represent a hydrogen atom, a halogen atom, a group chosen from an alkyl radical, a haloalkyl radical, an optionally substituted phenyl radical, a cyano group (CN), an optionally substituted alkyl-phenyl radical, an optionally substituted haloalkyl-phenyl radical, a carboxylic acid radical (COOH), an ester radical CO2R5 with R5 representing an alkyl radical, a phosphonic acid radical (PO(OH)2), a phosphonic acid ester radical P(O)(OR6a)(OR6b) with R6a representing a hydrogen atom or an alkyl radical, and R6b representing an alkyl radical, a sulfonic acid radical (SO3H), a sulfonic acid ester radical SO3R7 with R7 representing an alkyl radical or a haloalkyl radical, and an amide radical C(O)NR8aR8b, with R8a and R8b, independently of each other, representing a hydrogen atom or an alkyl radical, or together forming an alkyl radical; and in that: (ii) the monomer comprising ethylenic unsaturation is chosen from the monomers of the following formula (II):

[0016] [Chem.4] R9 R11 R10 R12 (H) in which: - R9 represents a hydrogen atom, or a fluorine atom; - R10 represents a hydrogen atom, or a fluorine atom; - R11 represents a hydrogen atom, an alkyl radical, a fluorine atom, or a chlorine atom; - R12 represents a hydrogen atom, or a group chosen from the following groups: * an alkyl radical, * a haloalkyl radical, * an optionally substituted aryl radical, * an optionally substituted alkyl-aryl radical, * an imidazolyl group, * an alkylimidazolium group, * a carbazoyl group, * a group of formula (III) following:

[0017] [Chem.5] * (III) in which the asterisk (*) represents the point of anchoring of the group of formula (III) to the carbon atom of the compound of formula (II), and R13 and R14, which may be identical or different, represent a hydrogen atom, an alkyl radical, an optionally substituted alkyl-aryl radical, an optionally substituted aryl radical, a glycidyl group, or R13 and R14 together with the nitrogen and carbon atoms of the group of formula (III) to which they are attached, form a heterocarbon ring comprising from 4 to 7 carbon atoms (including the carbon atom bearing the oxygen atom), * a group -OC(O)R15, with R15 representing an alkyl radical, a haloalkyl radical, an optionally substituted alkyl-aryl radical, an optionally substituted aryl radical, * a group -C(O)OR16, with R16 representing an alkyl radical, a haloalkyl radical, an optionally substituted alkylaryl radical, an optionally substituted aryl radical, * a phosphonic acid group (PO(OH)2), * a phosphonic acid ester group P(O)(OR17a)(OR17b), with R17a representing a hydrogen atom or an alkyl radical, and R17b representing an alkyl radical, * a sulfonic acid group (SO3H), * a sulfonic acid ester group SO3R18, with R18 representing an alkyl radical or a haloalkyl radical, and * an amide group C(O)NR19aR19b, with R19a and R19b, independently of each other, representing a hydrogen atom or an alkyl radical, or together forming an alkyl radical.

[0018] Thanks to this process, it is now possible to access in a simple manner, preferably with good yields, copolymers, preferably degradable, and whose degradability can be easily modulated by modifying the respective proportions of the monomers of formula (I) and (II).

[0019] During the process of the invention, the ring opening of the cyclic monomer (I) makes it possible to form within the copolymer units comprising thioester bonds, and ester bonds when X is an oxygen atom. Furthermore, a fraction of the cyclic monomer (I) can also react by radical polymerization with the monomer (II) without ring opening. The copolymer thus obtained then comprises, in addition to monomer units (I) with thioester bonds, and ester bonds when X is an oxygen atom, cyclic monomer units (I) having orthodithioester bonds and / or thioacetal bonds.

[0020] The degradability of the copolymer is therefore provided by the presence of thioester bonds, and possibly orthodithioester and / or thioacetal bonds, following the incorporation of the monomers of formula (I) into the backbone of the copolymer. The greater their proportion relative to the monomers of formula (II), the greater the de- gradability of the copolymer is high. Thus, after degradation, the length of the fragments obtained is inversely proportional to the quantity of monomers of formula (I) integrated into the backbone of the polymer. In addition, the chemical groups of the ends of the fragments obtained are functional and reactive. Furthermore, the thionolactide monomers of formula (I) used in the radical copolymerization reaction according to the process in accordance with the invention are easily synthesized according to conventional techniques known to those skilled in the art from non-sulfur precursors such as commercially available α-hydroxy acids, to form lactides which, by thionation, give thiolactides. In addition, the monomers (I) have the ability to react both with activated monomers such as styrene, its derivatives, or acrylates and with non-activated monomers such as vinyl esters.Finally, monomers of formula (II) are mostly commercially available.

[0021] According to the present invention, the term "degradable polymer" means a polymer whose backbone comprises bonds which can be easily broken, in particular by chemical hydrolysis, by aminolysis, or by enzymatic digestion, to lead to molecules of smaller size and possibly less polluting. According to the invention, said bonds are in particular thioester bonds, and possibly orthodithioester and / or thioacetal bonds.

[0022] According to the invention, the expression "thionolactide monomers of formula (I)" includes thionolactide as such corresponding to the compound of formula (I) in which R1, R3 = H, and R2, R4 = CH3; as well as any derivative of the aforementioned thionolactide corresponding to any of the compounds of formula (I) in which R1, R2, R3, R4 are as defined in the invention.

[0023] Thionolactide monomers (I)

[0024] X is an oxygen atom or a sulfur atom, and preferably an oxygen atom.

[0025] R1, R2, R3, and R4, independently of each other, represent an atom of hydrogen, a halogen atom, a group chosen from an alkyl radical, a haloalkyl radical, an optionally substituted phenyl radical, a cyano group (CN), an optionally substituted alkyl-phenyl radical, an optionally substituted haloalkyl-phenyl radical, a carboxylic acid radical (COOH), an ester radical CO2R5 with R5 representing an alkyl radical, a phosphonic acid radical (PO(OH)2), a phosphonic acid ester radical P(O)(OR6aR6b)2 with R6a representing a hydrogen atom or an alkyl radical, and R6b representing an alkyl radical, a sulfonic acid radical (SO3H), a sulfonic acid ester radical SO3R7 with R7 representing an alkyl radical or a haloalkyl radical, and an amide radical C(O)NR8aR8b, with R8a and R8b, independently of one of the other, representing a hydrogen atom or an alkyl radical, or together forming an alkyl radical.

[0026] The halogen atom as group R1, R2, R3, and / or R4 is preferably a fluorine atom.

[0027] The alkyl radical as group R1, R2, R3, and / or R4 may be linear or branched, cyclic or non-cyclic. The alkyl radical is preferably linear non-cyclic. The alkyl radical may comprise from 1 to 22 carbon atoms, preferably from 1 to 6 carbon atoms, and particularly preferably from 1 to 3 carbon atoms. An alkyl radical is advantageously a methyl or ethyl group.

[0028] In the invention, the term "haloalkyl" means an alkyl radical comprising one or more halogen atoms, preferably chosen from chlorine and fluorine atoms.

[0029] The haloalkyl radical as group R1, R2, R3, and / or R4 may be linear or branched, cyclic or non-cyclic. The haloalkyl radical is preferably linear non-cyclic. The haloalkyl radical may comprise from 1 to 18 carbon atoms, preferably from 1 to 6 carbon atoms, and particularly preferably from 1 to 3 carbon atoms. A haloalkyl radical is advantageously a trifluoromethyl, fluoromethyl, chloromethyl, or chloroethyl group.

[0030] In the invention, the term "optionally substituted phenyl" means that the phenyl radical as group R1, R2, R3, and / or R4 may be substituted by one or more substituents such as halogen atoms, preferably chosen from chlorine and fluorine atoms, alkyl groups, and haloalkyl groups.

[0031] The haloalkyl group as a substituent of the phenyl radical preferably comprises from 1 to 3 carbon atoms. It is advantageously a trifluoromethyl group.

[0032] The alkyl group as a substituent of the phenyl radical preferably comprises from 1 to 3 carbon atoms. It is advantageously a methyl group.

[0033] The phenyl radical substituted by one or more halogen atoms is preferably a pentafluorinated phenyl radical -C6F5.

[0034] An alkyl-phenyl radical optionally substituted as group R1, R2, R3, and / or R4 is a radical comprising at least one alkyl radical and at least one optionally substituted phenyl radical which are linked directly by a carbon (of the optionally substituted phenyl radical)-carbon (of the alkyl radical) covalent bond, the optionally substituted phenyl and alkyl radicals being as defined previously for the groups R1, R2, R3, and R4. The alkyl radical is directly linked via a carbon atom to the thionolactide. An optionally substituted alkyl-phenyl radical is advantageously a benzyl or pentafluorobenzyl radical.

[0035] A haloalkyl-phenyl radical optionally substituted as group R1, R2, R3, and / or R4 is a radical comprising at least one haloalkyl radical and at least one minus one optionally substituted phenyl radical which are directly linked by a carbon (of the optionally substituted phenyl radical)-carbon (of the haloalkyl radical) covalent bond, the optionally substituted phenyl and haloalkyl radicals being as defined previously for the groups R1, R2, R3, and R4. The haloalkyl radical is directly linked via a carbon atom to the thionolactide.

[0036] The alkyl radical as group R5 may be linear or branched, cyclic or non-cyclic. The alkyl radical is preferably linear non-cyclic. The alkyl radical may comprise from 1 to 22 carbon atoms, preferably from 1 to 6 carbon atoms, and particularly preferably from 1 to 3 carbon atoms. An alkyl radical is advantageously a methyl or ethyl group.

[0037] The alkyl radical as group R6a or R6b may be linear or branched, cyclic or non-cyclic. The alkyl radical is preferably linear non-cyclic. The alkyl radical may comprise from 1 to 22 carbon atoms, preferably from 1 to 6 carbon atoms, and particularly preferably from 1 to 3 carbon atoms. An alkyl radical is advantageously a methyl or ethyl group.

[0038] The alkyl radical as group R7 may be linear or branched, cyclic or non-cyclic. The alkyl radical is preferably linear non-cyclic. The alkyl radical may comprise from 1 to 22 carbon atoms, preferably from 1 to 6 carbon atoms, and particularly preferably from 1 to 3 carbon atoms. An alkyl radical is advantageously a methyl or ethyl group.

[0039] The haloalkyl radical as group R7 may be linear or branched, cyclic or non-cyclic. The haloalkyl radical is preferably linear non-cyclic. The haloalkyl radical may comprise from 1 to 18 carbon atoms, preferably from 1 to 6 carbon atoms, and particularly preferably from 1 to 3 carbon atoms. A haloalkyl radical is advantageously a trifluoromethyl group.

[0040] The alkyl radical as group R8a or R8b may be linear or branched, cyclic or non-cyclic. The alkyl radical is preferably linear non-cyclic. The alkyl radical may comprise from 1 to 22 carbon atoms, preferably from 1 to 6 carbon atoms, and particularly preferably from 1 to 3 carbon atoms. An alkyl radical is advantageously a methyl or ethyl group.

[0041] When the groups R8a and R8b together form an alkyl radical, a nitrogenous cycle is obtained in which R8a and R8b together form an alkyl radical, in particular comprising 5 carbon atoms (piperidine cycle).

[0042] Modulation of the R1, R2, R3, and R4 groups of thionolactide (I) makes it possible to increase its reactivity with respect to non-activated monomers (II) such as, for example, vinyl ester type monomers or with respect to activated monomers (II) such as, for example, acrylate, acrylamides, styrene, etc. type monomers.

[0043] R1, R2, R3, and R4, independently of each other, preferably represent a hydrogen atom, a halogen atom, a group selected from an alkyl radical, a haloalkyl radical, an optionally substituted phenyl radical, an optionally substituted alkyl-phenyl radical, and an optionally substituted haloalkyl-phenyl radical, and particularly preferably a hydrogen atom, a halogen atom, an alkyl radical, a haloalkyl radical, and an optionally substituted phenyl radical.

[0044] According to a preferred embodiment of the invention: * R1 = H or CH3, * R2 = H, CH3, C6H5, CF3, C6F5, C6H4-CF3, F, CH2F, CH2C1, or C2H4-C1, * R3 = H or CH3, * R4 = H, CH3, C6H5, CF3, C6F5, C6H4-CF3, F, CH2F, CH2C1, or C2H4-C1.

[0045] The thionolactide of formula (I) is advantageously chosen from the following thionolactides: (i) thionolactides in which R2 and R4 are as defined in the invention with the exclusion of hydrogen atoms, and particularly preferably are alkyl radicals, (ii) thionolactides in which R3 and R4 are as defined in the invention excluding hydrogen atoms, and particularly preferably are alkyl radicals, and (iii) thionolactides in which R1, R2, R3, or R4 are hydrogen atoms.

[0046] In the thionolactides (i), R1 and R3 are preferably hydrogen atoms.

[0047] In thionolactides (ii), R1 and R2 are preferably hydrogen atoms.

[0048] Thionolactides (i) and (ii) promote copolymerization with monomers (II) activated.

[0049] Thionolactides (iii) promote copolymerization with non-activated monomers (II).

[0050] According to a particular embodiment of the invention, the set of groups R1 and R2 is identical to the set of groups R3 and R4. This leads to a “symmetrical” thionolactide (I) which is easier to prepare.

[0051] The thionolactides of formula (I) are advantageously chosen from the thionolactides of formulas (1-1) to (1-13) presented in the following table:

[0052]

[0053] Among these thionolactides of formula (1-1) to (1-13), the thionolactides of formulas (1-1) and (1-13) are particularly preferred.

[0054] Monomers (II)

[0055] R9 preferably represents a hydrogen atom.

[0056] R10 preferably represents a hydrogen atom.

[0057] R11 preferably represents a hydrogen atom or an alkyl radical.

[0058] The alkyl radical as group R11 can be linear or branched, cyclic or not cyclic. The alkyl radical is preferably linear non-cyclic. The alkyl radical may comprise from 1 to 5 carbon atoms, and preferably from 1 to 3 carbon atoms. An alkyl radical is advantageously a methyl group.

[0059] The alkyl radical as group R12 may be linear or branched, cyclic or non-cyclic. The alkyl radical is preferably linear non-cyclic. The alkyl radical may contain from 1 to 22 carbon atoms, preferably from 1 to 10 carbon atoms, and particularly preferably from 1 to 5 carbon atoms, said alkyl radical being optionally substituted by a hydroxyl radical.

[0060] As examples of alkyl radicals as group R12, mention may be made of methyl, ethyl, iso-propyl, n-butyl, 2-butyl, iso-butyl, tert-butyl, n-pentyl, iso-pentyl, neo-pentyl, tert-pentyl, 2-methylbutyl, hexyl, n-octyl, iso-octyl, 2-ethyl-1-hexyl, 2,2,4-trimethylpentyl, nonyl, neo-decanyl, decyl, dodecyl, octadecyl, behenyl, or cyclohexylmethyl radicals, and preferably the methyl or hexyl radical.

[0061] The haloalkyl radical as group R12 may be linear or branched, cyclic or non-cyclic. The haloalkyl radical is preferably linear non-cyclic. The haloalkyl radical may comprise from 1 to 22 carbon atoms, and preferably from 1 to 5 carbon atoms.

[0062] The aryl radical as group R12 may be a monocyclic or polycyclic aromatic hydrocarbon group, optionally substituted by an alkyl radical comprising from 1 to 5 carbon atoms, or an alkoxyl radical comprising from 1 to 5 carbon atoms.

[0063] Examples of aryl radicals as group R12 include in particular phenyl, trityl, naphthalenyl, anthracenyl, and pyrenyl radicals. Among such radicals, the phenyl radical is particularly preferred.

[0064] The optionally substituted alkyl-aryl radical as group R12 is a radical comprising at least one alkyl radical and at least one optionally substituted aryl radical which are directly linked by a carbon (of the optionally substituted aryl radical)-carbon (of the alkyl radical) covalent bond, the optionally substituted aryl and alkyl radicals being as defined previously for group R12. The alkyl radical is directly linked via a carbon atom to the ethylenic function (double bond) of the monomer (II). An optionally substituted alkyl-aryl radical is advantageously a benzyl, p-methoxybenzyl, or pentafluorobenzyl radical.

[0065] The alkyl substituent of the alkylimidazolium radical as group R12 preferably comprises from 1 to 16 carbon atoms, and particularly preferably from 1 to 5 carbon atoms. The alkylimidazolium radical as group R12 preferably comprises a counterion selected from Br, BF4, and PF6.

[0066] Group of formula (III)

[0067] The alkyl radical as group R13 and / or R14 may be linear or branched, cyclic or non-cyclic. The alkyl radical is preferably linear. The alkyl radical may contain from 1 to 22 carbon atoms, and preferably from 1 to 5 carbon atoms.

[0068] As examples of alkyl radicals as group R13 and / or R14, mention may be made of methyl, ethyl, iso-propyl, n-butyl, 2-butyl, iso-butyl, tert-butyl, n-pentyl, iso-pentyl, neo-pentyl, tert-pentyl, 2-methylbutyl, hexyl, n- octyl, iso-octyl, 2-ethyl-l-hexyl, 2,2,4-trimethylpentyl, nonyl, neo-decanyl, decyl, dodecyl, octadecyl, behenyl, cyclohexylmethyl, adamantyl, and cy-clohexyl.

[0069] The aryl radical as group R13 and / or R14 may be a monocyclic or polycyclic aromatic hydrocarbon group, optionally substituted by an alkyl radical comprising from 1 to 5 carbon atoms, or an alkoxyl radical comprising from 1 to 5 carbon atoms.

[0070] As examples of aryl radicals as group R13 and / or R14, mention may in particular be made of phenyl, trityl, naphthalenyl, anthracenyl, and pyrenyl radicals. Among such radicals, the phenyl radical is particularly preferred.

[0071] The optionally substituted alkyl-aryl radical as group R13 and / or R14 is a radical comprising at least one alkyl radical and at least one optionally substituted aryl radical which are directly linked by a carbon (of the optionally substituted aryl radical)-carbon (of the alkyl radical) covalent bond, the optionally substituted aryl and alkyl radicals being as defined previously for groups R13 and R14. The alkyl radical is directly linked via a carbon atom to the nitrogen atom of formula (III) for R13 and to the carboxyl function of formula (III) for R14. An optionally substituted alkyl-aryl radical is advantageously a benzyl, or pentafluorobenzyl, radical.

[0072] When R13 and R14, together with the nitrogen and carbon atoms of the group of formula (III) to which they are linked, form a heterocarbon ring, this may in particular be a pyrrolidone, piperidone, or caprolactam ring.

[0073] According to a preferred embodiment of the invention, R13 and R14, which may be identical or different, represent a hydrogen atom, an alkyl radical, or R13 and R14 together with the nitrogen and carbon atoms of the group of formula (III) to which they are linked, form a heterocarbon ring comprising from 4 to 7 carbon atoms (including the carbon atom carrying the oxygen atom).

[0074] According to a particularly preferred embodiment, R13 and R14 are identical and represent a methyl radical or form, together with the nitrogen and carbon atoms of the group of formula (III) to which they are linked, a pyrrolidone or caprolactam ring.

[0075] Group -OC(O)R15

[0076] The alkyl radical as group R15 may be linear or branched, cyclic or non-cyclic. The alkyl radical is preferably linear and non-cyclic. The alkyl radical may contain from 1 to 22 carbon atoms, and preferably from 1 to 5 carbon atoms.

[0077] As examples of alkyl radicals as group R15, mention may be made of methyl, ethyl, iso-propyl, n-butyl, 2-butyl, iso-butyl, tert-butyl, n- pentyl, iso-pentyl, neo-pentyl, tert-pentyl, 2-methylbutyl, hexyl, n-octyl, iso-octyl, 2-ethyl-l-hexyl, 2,2,4-trimethylpentyl, nonyl, neo-decanyl, decyl, dodecyl, octadecyl, behenyl, cyclohexylmethyl, adamantyl, and cyclohexyl.

[0078] The aryl radical as group R15 may be a monocyclic or polycyclic aromatic hydrocarbon group, optionally substituted by an alkyl radical comprising from 1 to 5 carbon atoms, or an alkoxyl radical comprising from 1 to 5 carbon atoms.

[0079] Examples of aryl radicals as group R15 include in particular phenyl, trityl, naphthalenyl, anthracenyl, and pyrenyl radicals. Among such radicals, the phenyl radical is particularly preferred.

[0080] The optionally substituted alkyl-aryl radical as group R15 is a radical comprising at least one alkyl radical and at least one optionally substituted aryl radical which are directly linked by a carbon (of the optionally substituted aryl radical)-carbon (of the alkyl radical) covalent bond, the optionally substituted aryl and alkyl radicals being as defined previously for group R15. The alkyl radical is directly linked via a carbon atom to the carbon atom of the ester function. An optionally substituted alkyl-aryl radical is advantageously a benzyl, or pentafluorobenzyl, radical.

[0081] The haloalkyl radical as group R15 may be linear or branched, cyclic or non-cyclic. The haloalkyl radical is preferably linear non-cyclic. The haloalkyl radical may comprise from 1 to 22 carbon atoms, and preferably from 1 to 5 carbon atoms.

[0082] R15 preferably represents an alkyl or haloalkyl radical, and in particular Most preferably an alkyl radical such as a methyl or t-butyl radical.

[0083] Group -C(O)OR16

[0084] The alkyl radical as group R16 may be linear or branched, cyclic or non-cyclic. The alkyl radical is preferably linear and non-cyclic. The alkyl radical may contain from 1 to 22 carbon atoms, and preferably from 1 to 5 carbon atoms.

[0085] Examples of alkyl radicals as the R16 group include methyl, ethyl, isopropyl, n-butyl, 2-butyl, isobutyl, tert-butyl, n-pentyl, iso-pentyl, neo-pentyl, tert-pentyl, 2-methylbutyl, hexyl, n-octyl, iso-octyl, 2-ethyl-1-hexyl, 2,2,4-trimethylpentyl, nonyl, neodecanyl, decyl, dodecyl, octadecyl, behenyl, isobutyl, cyclohexylmethyl, adamantyl, and cyclohexyl radicals.

[0086] The aryl radical as group R16 may be a monocyclic or polycyclic aromatic hydrocarbon group, optionally substituted by an alkyl radical comprising from 1 to 5 carbon atoms, or an alkoxyl radical comprising from 1 with 5 carbon atoms.

[0087] Examples of aryl radicals as group R16 include in particular phenyl, trityl, naphthalenyl, anthracenyl, and pyrenyl radicals. Among such radicals, the phenyl radical is particularly preferred.

[0088] The optionally substituted alkyl-aryl radical as group R16 is a radical comprising at least one alkyl radical and at least one optionally substituted aryl radical which are directly linked by a carbon (of the optionally substituted aryl radical)-carbon (of the alkyl radical) covalent bond, the optionally substituted aryl and alkyl radicals being as defined previously for group R16. The alkyl radical is directly linked via a carbon atom to the carbon atom of the ester function. An optionally substituted alkyl-aryl radical is advantageously a benzyl, or pentafluorobenzyl, radical.

[0089] The haloalkyl radical as group R16 may be linear or branched, cyclic or non-cyclic. The haloalkyl radical is preferably linear non-cyclic. The haloalkyl radical may comprise from 1 to 22 carbon atoms, and preferably from 1 to 5 carbon atoms.

[0090] R16 preferably represents an alkyl radical, and particularly preferably a methyl or t-butyl radical.

[0091] The alkyl radical as group R17a or R17b may be linear or branched, cyclic or non-cyclic. The alkyl radical is preferably linear non-cyclic. The alkyl radical may comprise from 1 to 22 carbon atoms, preferably from 1 to 6 carbon atoms, and particularly preferably from 1 to 3 carbon atoms. An alkyl radical is advantageously a methyl or ethyl group.

[0092] The alkyl radical as group R18 may be linear or branched, cyclic or non-cyclic. The alkyl radical is preferably linear non-cyclic. The alkyl radical may comprise from 1 to 22 carbon atoms, preferably from 1 to 6 carbon atoms, and particularly preferably from 1 to 3 carbon atoms. An alkyl radical is advantageously a methyl or ethyl group.

[0093] The haloalkyl radical as group R18 may be linear or branched, cyclic or non-cyclic. The haloalkyl radical is preferably linear non-cyclic. The haloalkyl radical may comprise from 1 to 18 carbon atoms, preferably from 1 to 6 carbon atoms, and particularly preferably from 1 to 3 carbon atoms. A haloalkyl radical is advantageously a trifluoromethyl group.

[0094] The alkyl radical as group R19a or R19b may be linear or branched, cyclic or non-cyclic. The alkyl radical is preferably linear non-cyclic. The alkyl radical may comprise from 1 to 22 carbon atoms, preferably from 1 to 6 carbon atoms, and particularly preferably from 1 to 3 carbon atoms. An alkyl radical is advantageously a methyl or ethyl group.

[0095] When the groups R19a and R19b together form an alkyl radical, a nitrogenous cycle is obtained in which R19a and R19b together form an alkyl radical, in particular comprising 5 carbon atoms (piperidine cycle).

[0096] According to a particular embodiment, the monomer of formula (II) is chosen from: * vinyl ester monomers represented by the following formula (II-1):

[0097] [Chem.6] Ht J ri}=( 0 H O......« "b 15 (IM) in which R15 is as defined in the invention, * the a-olefin type monomers represented by the following formula (11-2):

[0098] [Chem.7] H R11 H R12 (H-2) in which R11 represents a hydrogen atom or an alkyl radical as defined in the invention, and R12 represents an alkyl radical or an optionally substituted aryl radical as defined in the invention, * N-vinyl type monomers represented by the following formula (III-1):

[0099] [Chem. 8] ■* O \ / / N U R (HM) in which R13 and R14 are as defined in the invention, * acrylate and alkacrylate monomers represented by the following formula (11-3):

[0100] [Chem.9] H R11 o h16 in which R11 represents a hydrogen atom or an alkyl radical as defined in the invention, and R16 represents an alkyl radical as defined in the invention.

[0101] Among the monomers of formula (II-1), mention may be made of vinyl acetate, vinyl pivalate, vinyl trifluoroacetate, vinyl chloroacetate, vinyl propionate, vinyl butyrate, vinyl neodecanoate (R15 = C9Hi9, mixture of isomers), and vinyl trifluorobutyrate. Among these monomers of formula (II-1), vinyl acetate and vinyl pivalate are particularly preferred.

[0102] Among the monomers of formula (11-2), mention may be made of ethylene and octene. Ethylene is particularly preferred.

[0103] Among the monomers of formula (III-1), we can in particular cite the monomers Acyclic N-vinyls such as N-vinylformamide, N-vinylacetamide and N-methyl-N-vinylacetamide, as well as cyclic N-vinyl monomers, (when R 13 and R14 form a heterocarbon ring together with the nitrogen and carbon atoms of the group of formula (III-1) to which they are bonded) such as N-vinylpyrrolidone, N-vinylpiperidone, and N-vinylcaprolactam. Among such monomers of formula (III-1), N-vinylacetamide and N-vinylpyrrolidone are particularly preferred.

[0104] Among the monomers of formula (II-3), mention may in particular be made of methyl acrylate, n-butyl acrylate, tert-butyl acrylate, 2-ethylhexyl acrylate, methyl methacrylate, tert-butyl methacrylate, isobornyl methacrylate or adamantyl methacrylate.

[0105] According to the process according to the invention, the proportion of monomers of formula (I) is preferably chosen such that the monomer(s) of formula (I) represent at most 50% by number relative to the total number of monomers of formulas (I) and (II). According to a particularly preferred embodiment, the monomer(s) of formula (I) represent from 5 to 30% approximately by number, even more preferably from 10 to 20% approximately by number, relative to the total number of monomers of formulas (I) and (II). Indeed, when the proportion of monomers of formula (I) is less than 5% by number, the degradability rate of the polymer is low, which is of little interest compared to non-degradable polymers. gradable. When the proportion of monomers of formula (I) is greater than 30% by number, the radical polymerization process by ring opening is altered, in particular slowed down.

[0106] For the purposes of the present invention, the term “radical polymerization initiator” means a chemical species capable of forming free radicals, i.e. radicals having one or more unpaired electrons on their external layer.

[0107] According to the process according to the invention, the radical polymerization initiator is preferably chosen from organic peroxides and hydroperoxides, azo derivatives, and radical-generating redox couples (redox systems).

[0108] Among the organic peroxides and hydroperoxides, mention may in particular be made of dilauroyl peroxide (LPO), t-butyl peroxyacetate, t-butyl peroxybenzoate, t-butyl peroxyoctoate, t-butyl peroxydodecanoate, t-butyl peroxyisobutyrate, t-amyl peroxypyvalate, t-butyl peroxypyvalate, di-isopropyl peroxydicarbonate, dicyclohexyl peroxydicarbonate, dicumyl peroxide, dibenzoyl peroxide, potassium peroxydisulfate, sodium peroxydisulfate, ammonium peroxydisulfate, cumene hydroperoxide and t-butyl hydroperoxide. Among these organic peroxides, LPO and t-butyl hydroperoxide are particularly preferred.

[0109] Among the azo derivatives, mention may in particular be made of 2,2' azobis(isobutyronitrile) or AIBN, 2,2'-azobis(2-cyano-2-butane), dimethyl-2,2'-azobisdimethylisobutyrate, 4,4'-azobis-(4-cyanopentanoic acid), 1,1'-azobis-(cyclohexanecarbonitrile), 2-(t-butylazo)-2-cyanopropane, 2,2'-azobis-[2-methyl-N(1,1)-bis(hydroxymethyl)-2-hydroxyethyl]propanamide, 2,2'-azobis-[2-methyl-N-hydroxyethyl]-propanamide, 2,2'-azobis-(N,N'-dimethyleneisobutyramidine) dihydrochloride, 2,2'-azobis-(2-amidinopropane), 2,2'-azobis-(N,N'-dimethylene isobutyramine), 2,2'-azobis-(2-methyl-N-[1,1bis-(hydroxymethyl)-2-hydroxyethyl]propionamide), 2,2'-azobis-(2-methyl-N-[1,1-bis-(hydroxymethyl)propionamide], 2,2'-azobis-[2-methyl-N-(2-hydroxyethyl)propionamide], 2,2'-azobis-(isobutyramide)dihydrate, 2,2'-azobis-(2,2,4-trimethylpentane) and 2,2'-azobis-(2-methylpropane).Among these azo derivatives, 2,2' azobis(isobutyronitrile) is particularly preferred.

[0110] The redox systems are for example chosen from systems comprising combinations such as: - mixtures of hydrogen peroxide, dialkyl peroxide, a hydroperoxide, a perester, a percarbonate and similar compounds and an iron salt, a titanium salt, zinc formaldehyde sulfoxylate or formaldehyde sulfoxylate sodium, and a reducing sugar, - mixtures of an alkali metal or ammonium persulfate, perborate or perchlorate with an alkali metal bisulfite, such as sodium metabisulfite, and a reducing sugar, and - mixtures of an alkali metal persulfate with an arylphosphinic acid, such as benzenephosphonic acid and the like, and a reducing sugar.

[0111] Among such redox systems, particularly preferred are combinations of ammonium persulfate and sodium formaldehyde sulfoxylate, and tert-butyl hydroperoxide and ascorbic acid.

[0112] It is also possible to use a photochemical initiator, in the ultraviolet (UV) or the visible. Among the initiators that can be used in the UV, we can notably cite 2,2-dimethoxy-2-phenylacetophenone, benzophenone / amine or benzophenone / alcohol couples. Among the initiators that can be used in the visible, we can mention thioxanthones. Finally, we can also use certain RAFT control agents of the xanthate or trithiocarbonate type which are also good photochemical initiators in the UV and visible.

[0113] The amount of radical polymerization initiator to be used according to the process according to the present invention is generally determined so that the amount of radicals generated is at most approximately 5 mol% relative to the total amount of monomers of formulae (I) and (II), and preferably at most approximately 1 mol%.

[0114] The radical ring-opening polymerization step of the monomers of formulae (I) and (II) can be carried out in bulk (without solvent) or in solution in a solvent, in particular chosen in such a way that the reaction medium remains homogeneous throughout the duration of the polymerization reaction. In general, the solvent is organic but it is not excluded to use an aqueous solvent such as water or a mixture of water and a co-solvent if the solubility of the monomer(s) justifies it. The polymerization of the monomers of formulae (I) and (II) can also be carried out in a heterogeneous medium, the polymer formed being insoluble in the reaction medium. The polymerization can also be carried out by the precipitating route, or in dispersion, emulsion or suspension.

[0115] According to a preferred embodiment of the invention, water, hydroalcoholic mixtures or organic solvents are used as reaction medium. Organic solvents are preferred.

[0116] The total quantity of polymerizable material in the reaction medium (total quantity of monomers of formula (I) and of formula (II)) can be 100% when the polymerization is carried out in bulk, i.e. without solvent. When the polymerization is carried out in a solvent, this total quantity can vary from 10% to 90% approximately in mass relative to the total mass of the reaction medium, preferably from 20 to 80% approximately by mass, and even more preferably from 30 to 60% approximately relative to the total mass of the reaction medium.

[0117] The polymerization step of the process according to the invention can be carried out at a temperature ranging from 5 to 150°C approximately, depending on the nature of the monomers of formulae (I) and (II) used during the reaction. According to a preferred embodiment of the process of the invention, the polymerization step is carried out at a temperature ranging from 20 to 130°C approximately, and even more preferably ranging from 40 to 110°C approximately.

[0118] The duration of the polymerization step generally varies from approximately 1 to 12 hours, and even more preferably from approximately 2 to 8 hours.

[0119] As indicated above, the polymerization step is preferably carried out only in the presence of the monomers of formulae (I) and (II) and a radical polymerization initiator, i.e. without a polymerization control agent. However, according to a variant of the process according to the invention, it is nevertheless possible to carry out the polymerization step in the presence of a polymerization control agent, thus making it possible to obtain copolymers, preferably degradable, with blocks, composition gradients, combs, star-grafted or even hyperbranched. Indeed, different processes for controlled radical polymerization are known, making it possible to obtain polymers with controlled architecture and mass. These processes are defined according to the chemical nature of the control agents involved.The present invention may involve a control agent for technologies of radical polymerization controlled by reversible addition-fragmentation chain transfer (RAFT), in particular in the presence of xanthates (MADIX), of atom transfer polymerization (ATRP), of iodine transfer polymerization (ITP), of reversible chain transfer-catalyzed radical polymerization (RCTP), of polymerization in the presence of organotellurium compounds (. "Tellurium-mediated Radical Polymerization" (TERP)), polymerization in the presence of organocobalt compounds (in English "Cobalt-Mediated radical Polymerization" (CoMP)), or reversible coordination polymerization (in English "Reversible Coordination-Mediated Polymerization" (RCMP)). These different technologies are described in the reference Polymer Chemistry 2018, 9, 4947-4967 and references cited.

[0120] The process of the invention thus makes it possible to produce a copolymer having at least less thioester bonds which are easily degradable.

[0121] In said process using a cyclic monomer (I) with at least one monomer comprising ethylenic unsaturation (II) in the presence of a radical polymerization initiator, a fraction of the cyclic monomer (I) can also be consumed during the polymerization without ring opening taking place. The copolymer thus obtained then comprises, in addition to thioester bonds by ring opening, cyclic monomer units (I) having ortho-dithioester and / or thioacetal bonds. These cyclic monomer units (I) having or-thodithioester and / or thioacetal bonds have the advantage of being sensitive to chemical attack and therefore potentially degradable.

[0122] The degradable copolymers obtained by implementing the process in accordance with the present invention are novel in themselves and as such constitute the second subject of the invention.

[0123] The present invention therefore also has as a second subject, a copolymer, preferably degradable, said copolymer being characterized in that it comprises at least thioester bonds, and that it results from radical polymerization by ring opening: (i) at least one cyclic monomer chosen from the thionolactides of the following formula (I):

[0124] [Chem. 10] $ R^ K ' R2 O' > R R3 • . O (I) in which: - X is an oxygen atom or a sulfur atom; - R1, R2, R3, and R4, independently of one another, represent a hydrogen atom, a halogen atom, a group chosen from an alkyl radical, a haloalkyl radical, an optionally substituted phenyl radical, a cyano group (CN), an optionally substituted alkyl-phenyl radical, an optionally substituted haloalkyl-phenyl radical, a carboxylic acid radical (COOH), an ester radical CO2R5 with R5 representing an alkyl radical, a phosphonic acid radical (PO(OH)2), a phosphonic acid ester radical P(O)(OR6a)(OR6b) with R6a representing a hydrogen atom or an alkyl radical, and R6b representing a radical alkyl, a sulfonic acid radical (SO3H), a sulfonic acid ester radical SO3R7 with R7 representing an alkyl radical or a haloalkyl radical, and an amide radical C(O)NR8aR8b, with R8a and R8b, independently of each other, representing a hydrogen atom or an alkyl radical, or together forming an alkyl radical; and (ii) at least one monomer comprising ethylenic unsaturation chosen from the monomers of formula (II) below:

[0125] [Chem. 11] R9 R11 \----- / 1^10 p12 (H) in which: - R9 represents a hydrogen atom, or a fluorine atom; - R10 represents a hydrogen atom, or a fluorine atom; - R11 represents a hydrogen atom, an alkyl radical, a fluorine atom, or a chlorine atom; - R12 represents a hydrogen atom, or a group chosen from the following groups: * an alkyl radical, * a haloalkyl radical, * an optionally substituted aryl radical, * an optionally substituted alkyl-aryl radical, * an imidazolyl group, * an alkylimidazolium group, * a carbazoyl group, * a group of formula (III) following:

[0126] [Chem. 12] * \ O n13 R14 rx (III) in which the asterisk (*) represents the anchoring point of the group of formula (III) to the carbon atom of the compound of formula (II), and R13 and R14, identical or different, represent a hydrogen atom, an alkyl radical, an alkyl-aryl radical even optionally substituted, an optionally substituted aryl radical, a glycidyl group, or R13 and R14 together with the nitrogen and carbon atoms of the group of formula (III) to which they are attached, form a heterocarbon ring comprising from 4 to 7 carbon atoms (including the carbon atom carrying the oxygen atom), * a group -OC(O)R15, with R15 representing an alkyl radical, a haloalkyl radical, an optionally substituted alkylaryl radical, an optionally substituted aryl radical, * a group -C(O)OR16, with R16 representing an alkyl radical, a haloalkyl radical, an optionally substituted alkylaryl radical, an optionally substituted aryl radical, * a phosphonic acid group (PO(OH)2), * a phosphonic acid ester group P(O)(OR17a)(OR17b), with R17a representing a hydrogen atom or an alkyl radical, and R17b representing an alkyl radical, * a sulfonic acid group (SO3H), * a sulfonic acid ester group SO3R18, with R18 representing an alkyl radical or a haloalkyl radical, and * an amide group C(O)NR19aR19b, with R19a and R19b, independently of each other, representing a hydrogen atom or an alkyl radical, or together forming an alkyl radical, in the presence of a radical polymerization initiator.

[0127] The preferences indicated above with reference to the first subject of the invention concerning the monomers of formulas (I) and (II), also apply to the second subject of the invention.

[0128] According to a particular and preferred embodiment of the invention, said copolymer results from the polymerization of thionolactide (I-1) and vinyl acetate, styrene, tert-butyl acrylate, methyl methacrylate, or vinyl pivalate.

[0129] According to a preferred embodiment of the second subject of the invention, the copolymer, preferably degradable, is a random copolymer.

[0130] According to the invention, the copolymer, preferably degradable, preferably has a number-average molar mass of approximately 2000 to 200000 g / mol, and even more preferably of approximately 5000 to 100000 g / mol.

[0131] The polymolecularity index of the polymer, preferably degradable, in accordance with the invention preferably varies from 1.2 to 4, and even more preferably from 1.4 to 3.

[0132] The level of thioester bonds in the main chain of the degradable copolymer in accordance with the invention is preferably at least 2% by number, preferably 2 to 20% by number, and even more preferably 5 to 15% by number, relative to the total number of bonds in the main chain.

[0133] The copolymer may further comprise orthodithioester and / or thioacetal linkages which are also degradable.

[0134] According to the invention, the term “main chain of the copolymer” means the longest chain of bonds, i.e. without including the bonds of the side substituents.

[0135] Due to their degradable nature, the copolymers in accordance with the present invention can be useful in any type of industry. By way of example, mention may in particular be made of the biomedical field, agriculture, cosmetics, oil extraction, detergents, release of active products and packaging.

[0136] For the copolymers of the invention which would only have low degradability, or even no degradability, these could also be useful in the medical field, in particular for dental fillings, or any type of field for which it is desired to reduce the shrinkage associated with polymerization.

[0137] The invention also has as a third object the use of at least one thionolactide corresponding to formula (I) as defined in the first object of the invention as precursor monomer in a radical polymerization.

[0138] The radical polymerization is as defined in the first subject of the invention.

[0139] Certain thionolactides corresponding to formula (I) are new in themselves and constitute a fourth object of the invention.

[0140] The invention thus has as its fourth subject a thionolactide for the implementation of a method as defined in the first subject of the invention, said thiolactide corresponding to the following formula (!):

[0141] [Chem. 13] in which: - X, R1, R2, R3, and R4 are as defined in the first subject of the invention, - excluding thionolactides (1-1) and (1-2) as defined in the invention.

[0142] Preferably, the thionolactide of formula (!') is chosen from the thionolactides of formulas (1-3) to (1-13) as described in the invention.

[0143] The lactides precursors of the thionolactides of formula (I) or (!') as described in the invention can be obtained by dimerization of corresponding alpha-hydroxy acids or, in the case of compound (1-13), by reaction of alpha-hydroxyisobutyric acid with chloroacetyl chloride. Single or double thionation of lactides can be carried out in the presence of P4Si0 and hexamethyldisiloxane (HMDSO). Brief description of the drawings

[0144] The attached drawing illustrates the invention:

[0145] [Fig-1] [Fig.l] illustrates the chemical degradation of a polymer conforming to the invention.

[0146] Other characteristics and advantages of the present invention will appear in light of the description of examples presented below to which the invention is however not limited. Examples

[0147] The size exclusion chromatography analyses were carried out with a system equipped with two Styragel H3R and HR4E columns, a refractometric detector and a light scattering detector, for analysis in tetrahydrofuran (THF) at 35°C and a flow rate of 1 ml / min.

[0148] Example 1: Synthesis of a degradable CPI copolymer based on styrene and thionolactide of formula (1-1) according to the process of the invention

[0149] 1.1 First step: synthesis of thionolactide of formula (1-1)

[0150] In a two-necked flask topped with a condenser, P4Si0 (13 mmol, 5.8 g), racemic lactide (34.9 mmol, 5 g), hexamethyldisiloxane (HMDSO) (86.9 mmol, 14.1 g) and 50 mL of anhydrous acetonitrile were introduced. The resulting mixture was heated at reflux for 48 hours. Then, the reaction medium was cooled to room temperature, filtered using a layer of silica gel (50 g), and washed with dichloromethane (DCM). The filtrate was evaporated under reduced pressure and purified by column chromatography (eluent cyclohexane / ethyl acetate 8 / 2). The thionolactide was recrystallized four times to obtain crystals with a yield of 33% (1.8 g). The obtained crystals were sublimated before their use in polymerization at 60°C and at a pressure of 102 mbar.

[0151] 'H NMR (CDC13, 300 MHz): 5.06 ppm (q, 1H), 4.98 ppm (q, 1H), 1.79 ppm (d, 3H), 1.76 ppm (d, 3H).

[0152] 13C NMR (CDC13, 126 MHz): 211.4 ppm, 167.5 ppm, 78.4 ppm, 75.1 ppm, 19.3 ppm, 15.5 ppm.

[0153] 1.2 Second step: synthesis of the poly(styrene-co-thionolactide) CPI copolymer

[0154] 6 mg (0.025 mmol) of azobis(cyanocyclohexane) (VAZO-88), 0.08 g were mixed (0.5 mmol) of thionolactide (1-1) obtained in the previous step, 0.468 g (4.5 mmol) of styrene, and 10 mg of naphthalene as an internal standard, to form a solution. The Thionolactide (monomer of formula (I-1)) represents 10% (in mole) relative to styrene (monomer of formula (II)). The solution was transferred into a Carius tube which was sealed under vacuum after three degassing cycles. The tube was then placed in an oil bath at 100°C for 5 hours. The polymerization was stopped by rapid cooling. After opening the tube, a portion of the solution was transferred into an NMR tube to determine the conversion of thionolactide (I-1) after 5 hours of reaction.

[0155] The conversion to monomer was determined by hydrogen nuclear magnetic resonance (H NMR). To do this, the signal at 7.8 ppm of naphthalene as an internal standard was integrated as corresponding to 1 and was compared to a signal at 5.10-4.95 ppm which corresponds to two hydrogen atoms of thionolactide and compared with the result of the integral at a reaction time equal to 0 hours. The conversion of thionolactide (1-1) after a reaction time of X hours can thus be determined according to the following equation 1:

[0156] [Math.l] Conversion (Z-1) = 1-

[0157] The monomer conversion, determined by hydrogen nuclear magnetic resonance (H NMR), was 58% for thionolactide (1-1) and 82% for styrene. The residual monomers were evaporated and the number-average molar mass (Mn), as well as the polydispersity index (Mw / Mn) of the CPI copolymer were measured by size exclusion chromatography (eluent: tetrahydrofuran THF) with a PMMA-based calibration curve: Mn = 13200 g / mol; Mw / Mn = 2.3.

[0158] Example 2: Synthesis of a degradable copolymer CP2 based on tert-butyl acrylate and thionolactide of formula (1-1) according to the process of the invention

[0159] 5.3 mg (0.022 mmol) of azobis(cyanocyclohexane) (VAZO-88), 0.07 g (0.44 mmol) of thionolactide (1-1) obtained in Example 1, 0.504 g (3.9 mmol) of tert-butyl acrylate, and 10 mg of naphthalene as an internal standard were mixed to form a solution. Thionolactide (monomer of formula (1-1)) represents 10% (by mole) relative to tert-butyl acrylate (monomer of formula (II)). The solution was transferred to a Carius tube which was sealed under vacuum after three degassing cycles. The tube was then placed in an oil bath at 100°C for 5 hours. The polymerization was stopped by rapid cooling. After opening the tube, part of the solution was transferred into an NMR tube to determine the conversion of thionolactide (1-1) after 5 h of reaction.

[0160] The conversion to monomer, determined by hydrogen nuclear magnetic resonance (H NMR), as explained in Example 1 was 34% for the thio- nolactide (1-1) and 33% for tert-butyl acrylate. The residual monomers were evaporated and the number-average molar mass (Mn) and the polydispersity index (Mw / Mn) of the copolymer poly(tert-butyl acrylate-co-thionolactide) CP2 were measured by size exclusion chromatography (eluent: THF) with a PMMA-based calibration curve: Mn = 8000 g / mol; Mw / Mn = 1.7.

[0161] Example 3: Synthesis of a degradable copolymer CP3 based on methyl methacrylate and thionolactide of formula (1-1) according to the process of the invention

[0162] 6.1 mg (0.025 mmol) of azobis(cyanocyclohexane) (VAZO-88), 0.08 g (0.5 mmol) of thionolactide (1-1) obtained in Example 1, 0.45 g (4.5 mmol) of methyl methacrylate, and 10 mg of naphthalene as an internal standard were mixed to form a solution. Thionolactide (monomer of formula (1-1)) represents 10% (by mole) relative to methyl methacrylate (monomer of formula (II)). The solution was transferred into a Carius tube which was sealed under vacuum after three degassing cycles. The tube was then placed in an oil bath at 100°C for 5 hours. The polymerization was stopped by rapid cooling. After opening the tube, part of the solution was transferred into an NMR tube to determine the conversion of thionolactide (1-1) after 5 h of reaction.

[0163] The conversion to monomer, determined by hydrogen nuclear magnetic resonance (H NMR), as explained in Example 1 was 10% for thionolactide (1-1) and 64% for methyl methacrylate. The residual monomers were evaporated and the number-average molar mass (Mn), as well as the polydispersity index (Mw / Mn) of the poly(methyl methacrylate-co-thionolactide) copolymer CP3 were measured by size exclusion chromatography (eluent: THF) with a PMMA-based calibration curve: Mn = 7000 g / mol; Mw / Mn = 1.9.

[0164] Example 4: Synthesis of a degradable copolymer CP4 based on vinyl pivalate and thionolactide of formula (1-1) according to the process of the invention

[0165] 5.4 mg (0.022 mmol) of azobis(cyanocyclohexane) (VAZO-88), 0.07 g (0.44 mmol) of thionolactide (1-1) obtained in Example 1, 0.504 g (3.9 mmol) of vinyl pivalate, and 10 mg of naphthalene as an internal standard were mixed to form a solution. Thionolactide (monomer of formula (1-1)) represents 10% (by mole) relative to vinyl pivalate (monomer of formula (II)). The solution was transferred into a Carius tube which was sealed under vacuum after three degassing cycles. The tube was then placed in an oil bath at 70°C for 16 hours. The polymerization was stopped by rapid cooling. After opening the tube, part of the solution was transferred into an NMR tube to determine the conversion of thionolactide (1-1) after 16 h of reaction.

[0166] The conversion to monomer, determined by nuclear magnetic resonance of hydrogen (*H NMR), as explained in Example 1 was 100% for thionolactide (1-1) and 64% for vinyl pivalate. The residual monomers were evaporated and the number-average molar mass (Mn) and the polydispersity index (Mw / Mn) of the poly(vinyl pivalate-co-thionolactide) copolymer CP4 were measured by size exclusion chromatography (eluent: THF) with a PMMA-based calibration curve: Mn = 12100 g / mol; Mw / Mn = 2.1.

[0167] Example 5: Chemical degradation of a degradable copolymer CP2 based on tert-butyl acrylate and thionolactide of formula (1-1)

[0168] 10 mg of the CP2 copolymer of Example 2 were diluted in 1 ml of THF and 1 ml of a bleach solution (aqueous NaOCl solution comprising 11-15% active chlorine) was added. The resulting mixture was kept stirring in a sealed tube for 14 days at room temperature. The solvent was evaporated under reduced pressure, then the residue was dissolved in THF and analyzed by size exclusion chromatography.

[0169] [Fig.l] shows the behavior of CP2 in relative value An (i.e. difference between the refractive index of the analyzed sample and that of the solvent) as a function of the retention time (in min) before contact with bleach (CP2 in THF, Mn = 8000 g / mol, Mw / Mn = 1.7, [Fig.l] a), of the residue obtained after contacting CP2 with bleach (Mn = 2100 g / mol, Mw / Mn = 1.5, [Fig.l] b), and of CP2 diluted in THF and left at room temperature for 30 days (Mn = 6400 g / mol, Mw / Mn = 2.0, [Fig.l] c).

[0170] It appears that after degradation of the CP2 copolymer by bleach, the molar mass distribution is significantly shifted in the low molar mass range compared to the copolymer before treatment, attesting to the degradation of the skeleton resulting from the presence of thioester bonds.

[0171] Example 6: Synthesis of a degradable copolymer CP5 based on n-butyl acrylate and thionolactide of formula (1-1) according to the process of the invention

[0172] 4.3 mg (0.022 mmol) of azobis(isobutyronitrile) (AIBN), 0.07 g (0.44 mmol) of thionolactide (1-1) obtained in Example 1, 0.504 g (3.9 mmol) of n-butyl acrylate, and 10 mg of naphthalene as an internal standard were mixed to form a solution. Thionolactide (monomer of formula (1-1)) represents 10% (by mole) relative to n-butyl acrylate (monomer of formula (II)). The solution was transferred into a Carius tube which was sealed under vacuum after three degassing cycles. The tube was then placed in an oil bath at 70°C for 3 hours. The polymerization was stopped by rapid cooling. After opening the tube, part of the solution was transferred into an NMR tube to determine the conversion of thionolactide (1-1).

[0173] The conversion to monomer, determined by nuclear magnetic resonance of hydrogen (*H NMR), as explained in Example 1 was 41% for thionolactide (1-1) and 87% for n-butyl acrylate. The residual monomers were evaporated and the number average molar mass (Mn) and the polydispersity index (Mw / Mn) of the copolymer poly(n-butyl acrylate-co-thionolactide) CP5 were measured by size exclusion chromatography (eluent: THF) with a PMMA-based calibration curve: Mn = 98000 g / mol; Mw / Mn = 1.7.

[0174] Example 7: Synthesis of thionolactide of formula (1-3)

[0175] In a two-necked flask topped with a condenser, P4Si0 (10.7 mmol, 4.8 g), glycolide (34.9 mmol, 5 g), hexamethyldisiloxane (HMDSO) (72 mmol, 11.7 g) and 50 mL of anhydrous acetonitrile were introduced. The resulting mixture was heated at reflux for 5 hours. Then, the reaction medium was cooled to room temperature, and the solvent was evaporated. The product was purified a first time by column chromatography (eluent dichloromethane), then the collected fractions were purified again by column chromatography (50 g of silica gel, eluent 30% ethyl ether / 70% petroleum ether). Yield: 20%, 1.1 g.

[0176] 'H NMR (CDC13, 300 MHz): 5.2 pmm (s, 2H), 5.0 pmm (s, 2H).

[0177] 13C NMR (CDC13, 126 MHz): 206, 165, 78, 33.

[0178] Example 8: Synthesis of thionolactide of formula (1-13)

[0179] Step 1: synthesis of 2,2-dimethylglycolide

[0180] In a two-necked flask topped with a condenser, 4.6 g (44.2 mmol) of alpha-hydroxyisobutyric acid, 5 g of chloroacetyl chloride (44.2 mmol) in 5 ml of acetonitrile were introduced. The mixture was heated to 80°C with stirring overnight. After cooling to room temperature, the reaction mixture was diluted in 200 ml of acetonitrile, then 9.6 g of triethylamine were added dropwise. The solution obtained was then heated to 70°C for 6 hours. After filtration, the product was obtained by evaporation of the solvent. Yield: 35%, 2.2 g.

[0181] 'H NMR (CDC13, 300 MHz): 5.0 pmm (s, 2H), 1.71 pmm (s, 6H).

[0182] 13C NMR (CDC13, 126 MHz): 167, 164, 75, 73, 24.

[0183] Step 2: synthesis of 2,2-dimethylthioglycolide (1-13)

[0184] In a two-necked flask topped with a condenser, P4Si0 (3.8 mmol, 1.7 g), 2,2-dimethylglycolide from step 1 (15.2 mmol, 2.2 g), hexamethyldisiloxane (HMDSO) (25.5 mmol, 4.14 g) and 20 mL of anhydrous acetonitrile were introduced, the whole being inerted by bubbling argon. The resulting mixture was heated at reflux for 16 hours. Then, the reaction medium was cooled to room temperature, and the solvent was evaporated. The product was purified a first time by column chromatography (eluent dichloromethane), then the collected fractions were purified again by column chromatography (50 g of silica gel, eluent 30% ethyl ether / 70% petroleum ether). Yield: 30%, 0.7 g.

[0185] 'H NMR (CDC13, 300 MHz): 5.2 ppm (s, 2H), 1.76 ppm (s, 6H).

[0186] 13C NMR (CDC13, 126 MHz): 206, 167, 82, 73, 24.

Claims

Claims

1. Process for the preparation of at least one copolymer, preferably degradable, said process comprising at least one step of radical polymerization by ring opening of at least one cyclic monomer with at least one monomer comprising ethylenic unsaturation, in the presence of a radical polymerization initiator, said process being characterized in that: (i) the cyclic monomer is chosen from the thionolactides of formula (I) below: [Chem. 14] S R1 oA^2 R3- . -O H' RX (I) in which: - X is an oxygen atom or a sulfur atom; - R1, R2, R3, and R4, independently of one another, represent a hydrogen atom, a halogen atom, a group chosen from an alkyl radical, a haloalkyl radical, an optionally substituted phenyl radical, a cyano group, an optionally substituted alkyl-phenyl radical, an optionally substituted haloalkyl-phenyl radical, a carboxylic acid radical, an ester radical CO2R5 with R5 representing an alkyl radical, a phosphonic acid radical, a phosphonic acid ester radical P(O)(OR6a)(OR6b) with R6a representing a hydrogen atom or an alkyl radical, and R6b representing an alkyl radical, a sulfonic acid radical, a sulfonic acid ester radical SO3R7 with R7 representing an alkyl radical or a haloalkyl radical, and an amide radical C(O)NR8aR8b, with R8a and R8b, independently of one another, representing a hydrogen atom or an alkyl radical, or together forming an alkyl radical; and in that: (ii) the monomer comprising ethylenic unsaturation is chosen from the monomers of the following formula (II): [Chem. 15] R 9 R 11 )..........X R^ (U) in which: - R9 represents a hydrogen atom, or a fluorine atom; - R10 represents a hydrogen atom, or a fluorine atom; - R11 represents a hydrogen atom, an alkyl radical, a fluorine atom, or a chlorine atom; - R12 represents a hydrogen atom, or a group chosen from the following groups: * an alkyl radical, * a haloalkyl radical, * an optionally substituted aryl radical, * an optionally substituted alkyl-aryl radical, * an imidazolyl group, * an alkylimidazolium group, * a carbazoyl group, * a group of formula (III) following: [Chem. 16] * \ P R 6 R 14 (III) in which the asterisk (*) represents the point of anchoring of the group of formula (III) to the carbon atom of the compound of formula (II), and R13 and R14, which may be identical or different, represent a hydrogen atom, an alkyl radical, an optionally substituted alkyl-aryl radical, an optionally substituted aryl radical, a glycidyl group, or R13 and R14 together with the nitrogen and carbon atoms of the group of formula (III) to which they are attached, form a heterocarbon ring comprising from 4 to 7 carbon atoms, * a group -OC(O)R15, with R15 representing an alkyl radical, a haloalkyl radical, an optionally substituted alkyl-aryl radical, an optionally substituted aryl radical, * a group -C(O)OR16, with R16 representing an alkyl radical, a haloalkyl radical, an optionally substituted alkyl-aryl radical, an optionally substituted aryl radical, * a phosphonic acid group, * a phosphonic acid ester group P(O)(OR17a)(OR17b), with R17a representing a hydrogen atom or an alkyl radical, and R17b representing an alkyl radical, * a sulfonic acid group, * a sulfonic acid ester group SO3R18, with R18 representing an alkyl radical or a haloalkyl radical, and * an amide group C(O)NR19aR19b, with R19a and R19b, independently of each other, representing a hydrogen atom or a radical alkyl, or together forming an alkyl radical.

2. A method according to claim 1, characterized in that R1, R2, R3, and R4, independently of one another, represent a hydrogen atom, a halogen atom, a group chosen from an alkyl radical, a haloalkyl radical, an optionally substituted phenyl radical, an optionally substituted alkyl-phenyl radical, and an optionally substituted haloalkyl-phenyl radical.

3. Method according to claim 1 or 2, characterized in that: * R1 = H or CH3, * R2 = H, CH3, C6H5, CF3, C6F5, C6H4-CF3, F, CH2F, CH2C1, or C2H4-C1, * R3 = H or CH3, * R4 = H, CH3, C6H5, CF3, C6F5, C6H4-CF3, F, CH2F, CH2C1, or c2h4-ci.

4. Process according to any one of the preceding claims, characterized in that the thionolactide of formula (I) is chosen from the following thionolactides: (i) thionolactides in which R2 and R4 are as defined in claim 1 excluding hydrogen atoms, (ii) thionolactides in which R3 and R4 are as defined in claim 1 excluding hydrogen atoms, and (iii) thionolactides in which R1, R2, R3, or R4 are hydrogen atoms.

5. Process according to any one of the preceding claims, characterized in that the thionolactides of formula (I) are chosen from the thionolactides of formulas (I-1) to (I-13) presented in the table following : [Tables 2] 0"' .! (1-1) -s V’ ...ô O s ' '■ (I-2) b b-o O < b o o-V8 (i-4) . k...o z X X ' b~"(. • LÇ O zz. c Q" o c (!-6) 'Tï / 'Tl - CH. -in w ■' b-î. p b “ O Xx .6 „ 0' (f-8) a---, ,>s 9' r X- ° 0' Y (i-9) ■ o S- Xv 0-W) F F 9"" cX (1-11) lù lu en u x y~q >X C 0^ (1-1 X y" 2) 9........rs <x° (f-13)

6.

7. Process according to any one of the preceding claims, characterized in that R9 represents a hydrogen atom, R10 represents a hydrogen atom, and R11 represents a hydrogen atom or an alkyl radical. Process according to any one of the preceding claims, characterized in that the monomer of formula (II) is chosen from: * vinyl ester type monomers represented by the following formula (II-1): [Chem. 17] HH \ ......... / / —K \ w HO C R15 (H-1) * the α-olefin type monomers represented by the following formula (II-2): [Chem. 18] H R11 X / H R12 (II-2) in which R1' represents a hydrogen atom or an alkyl radical, and R12 represents an alkyl radical or an optionally substituted aryl radical, * the N-vinyl type monomers represented by the following formula (III-1): [Chem. 19] O N......-f P14 _ 13 (IIM) * the acrylate and alkacrylate type monomers represented by the following formula (II-3): [Chem. 20] H R11 " ; ■ d R1fJ (11-3) in which R11 represents a hydrogen atom or an alkyl radical and R16 represents an alkyl radical.

8. Process according to any one of the preceding claims, characterized in that the proportion of monomers of formula (I) is chosen such that the monomer(s) of formula (I) represent at most 50% by number relative to the total number of monomers of formulas (I) and (II).

9. Process according to any one of the preceding claims, characterized in that the step of radical polymerization by ring opening of the monomers of formulae (I) and (II) is carried out in bulk or in solution in a solvent.

10.

11.

12. Process according to any one of the preceding claims, characterized in that the polymerization is carried out in a solvent and in that the total quantity of monomers of formula (I) and of formula (II) varies from 30 to 60% by mass relative to the total mass of the reaction medium. Process according to any one of the preceding claims, characterized in that the polymerization step is carried out at a temperature ranging from 5 to 150°C. Copolymer, preferably degradable, said copolymer being characterized in that it comprises at least thioester bonds, and that it results from the radical polymerization by ring opening: (i) of at least one cyclic monomer chosen from the thionolactides of formula (I) below: [Chem.21] R1 o R34x O A4 t î K x (I) in which: - X is an oxygen atom or a sulfur atom; - R1, R2, R3, and R4, independently of one another, represent a hydrogen atom, a halogen atom, a group chosen from an alkyl radical, a haloalkyl radical, an optionally substituted phenyl radical, a cyano group, an optionally substituted alkyl-phenyl radical, an optionally substituted haloalkyl-phenyl radical, a carboxylic acid radical, an ester radical CO2R5 with R5 representing an alkyl radical, a phosphonic acid radical, a phosphonic acid ester radical P(O)(OR6a)(OR6b) with R6a representing a hydrogen atom or an alkyl radical, and R6b representing an alkyl radical, a sulfonic acid radical, a sulfonic acid ester radical SO3R7 with R7 representing an alkyl radical or a haloalkyl radical, and an amide radical C(O)NR8aR8b, with R8a and R8b, independently of one another, representing a hydrogen atom or an alkyl radical, or together forming an alkyl radical; and (ii) at least one monomer comprising ethylenic unsaturation chosen from the monomers of the following formula (II): [Chem. 22] r9 r11 R12 (II) in which: - R9 represents a hydrogen atom, or a fluorine atom; - R10 represents a hydrogen atom, or a fluorine atom; - R11 represents a hydrogen atom, an alkyl radical, a fluorine atom, or a chlorine atom; - R12 represents a hydrogen atom, or a group chosen from the following groups: * an alkyl radical, * a haloalkyl radical, * an optionally substituted aryl radical, * an optionally substituted alkyl-aryl radical, * an imidazolyl group, * an alkylimidazolium group, * a carbazoyl group, * a group of formula (III) following: [Chem. 23] O R14 (III) in which the asterisk (*) represents the point of anchoring of the group of formula (III) to the carbon atom of the compound of formula (II), and R13 and R14, which may be identical or different, represent a hydrogen atom, an alkyl radical, an optionally substituted alkyl-aryl radical, an optionally substituted aryl radical, a glycidyl group, or R13 and R14 together with the nitrogen and carbon atoms of the group of formula (III) to which they are attached, form a heterocarbon ring comprising from 4 to 7 carbon atoms (including the carbon atom bearing the oxygen atom), * a group -OC(O)R15, with R15 representing an alkyl radical, a haloalkyl radical, an optionally substituted alkyl-aryl radical, an optionally substituted aryl radical, * a group -C(O)OR16, with R16 representing an alkyl radical, a haloalkyl radical, an optionally substituted alkyl-aryl radical, an optionally substituted aryl radical, * a phosphonic acid group, * a phosphonic acid ester group P(O)(OR17a)(OR17b), with R17a representing a hydrogen atom or an alkyl radical, and R17b representing an alkyl radical, * a sulfonic acid group, * a sulfonic acid ester group SO3R18, with R18 representing an alkyl radical or a haloalkyl radical, and * an amide group C(O)NR19aR19b, with R19a and R19b, independently of each other, representing a hydrogen atom or an alkyl radical, or together forming an alkyl radical, in the presence of a radical polymerization initiator.

13. Copolymer according to claim 12, characterized in that it results from the polymerization of thionolactide (1-1) as defined in claim 5 and vinyl acetate, styrene, tert-butyl acrylate, methyl methacrylate, or vinyl pivalate.

14. Copolymer according to claim 12 or 13, characterized in that it has a rate of thioester bonds in the main chain of at least 2% by number, relative to the total number of bonds in the main chain.

15. Use of at least one thionolactide corresponding to formula (I) as defined in any one of claims 1 to 5, as precursor monomer in a radical polymerization.

16. Thionolactide for carrying out a method as defined in any one of claims 1 to 11, corresponding to the following formula (!): [Chem. 24] R—-L .0 h

17. (0 in which: - X, R1, R2, R3, and R4 are as defined in any one of claims 1 to 5, - excluding thionolactides (1-1) and (1-2) as defined in claim 5. Thionolactide according to claim 16 chosen from thionolactides of formulas (1-3) to (1-13) as defined in claim 5.

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