Method for radical polymerisation of thionolactides

Abstract

The present invention relates to a method for preparing copolymers, preferably degradable or biodegradable copolymers, from thionolactides. The present invention more particularly relates to a method for preparing copolymers, preferably degradable copolymers, by ring-opening radical polymerisation, employing in particular at least one thiolactide monomer. The present invention also relates to the copolymers, preferably degradable copolymers, obtained by implementing this method, to the use of said thionolactide monomer as a precursor monomer in a radical polymerisation, and to specific thionolactides.

Description

[0001] Process for the radical polymerization of thionolactides

[0002] The present invention relates to a process for preparing copolymers, preferably degradable or biodegradable, from thionolactides.

[0003] More particularly, the present invention relates to a process for preparing copolymers, preferably degradable, by radical polymerization by ring opening using in particular at least one monomer of thionolactide type, to the copolymers, preferably degradable, obtained by the implementation of this process, to the use of said monomer of thionolactide type as precursor monomer in a radical polymerization, as well as to specific thionolactides.

[0004] The majority of synthetic polymers are currently synthesized by free radical polymerization of vinyl monomers such as 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 ème 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.

[0005] One of the main disadvantages of polymers produced by radical polymerization is that they are difficult to degrade. Indeed, the individual monomer units are linked together by carbon-carbon (CC) bonds, which are very resistant to degradation. This can lead to environmental damage and also limits the application of these polymers in the medical field, where it is important to avoid the accumulation of high-molecular-weight polymers in the body.

[0006] One way to introduce 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 the vinyl or exo-methylene type carries a degradable functionality, this can then be incorporated into the polymer backbone, making it itself degradable.

[0007] 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:

[0008] 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 to n-butylacrylate.

[0011] Therefore, there is a need for synthetic processes that allow simple access, preferably with good yields, to new synthetic polymers having varied structures, and preferably being 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 can achieve these goals, the process offering 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: in which:

[0015] - X is an oxygen atom or a sulfur atom;

[0016] - R 1 , R 2 , R 3 , and R 4, independently of each other, 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 CO2R 5 with R 5 representing an alkyl radical, a phosphonic acid radical (PO(OH)2), a phosphonic acid ester radical P(O)(OR 6a )(GOLD 6b ) with R 6a representing a hydrogen atom or an alkyl radical, and R 6b representing an alkyl radical, a sulfonic acid radical (SO3H), a sulfonic acid ester radical SO3R 7 with R 7 representing an alkyl radical or a haloalkyl radical, and an amide radical C(O)NR 8a R 8b , with R 8a and R 8b, independently of one another, representing a hydrogen atom or an alkyl radical, or together forming an alkyl radical; and in that:

[0017] (ii) the monomer comprising ethylenic unsaturation is chosen from the monomers of the following formula (II): in which:

[0018] - R 9 represents a hydrogen atom, or a fluorine atom; - R 10 represents a hydrogen atom, or a fluorine atom;

[0019] - R 11 represents a hydrogen atom, an alkyl radical, a fluorine atom, or a chlorine atom;

[0020] - R 12 represents a hydrogen atom, or a group chosen from the following groups:

[0021] * an alkyl radical,

[0022] * a haloalkyl radical,

[0023] * an optionally substituted aryl radical,

[0024] * an optionally substituted alkyl-aryl radical,

[0025] * an imidazolyl group,

[0026] * an alkylimidazolium group,

[0027] * a carbazoyl group,

[0028] * a group of formula (III) following: 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 R 13 and R 14 , 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 R 13 and R 14 together with the nitrogen and carbon atoms of the group of formula (III) to which they are bound, form a heterocarbon ring comprising from 4 to 7 carbon atoms (including the carbon atom bearing the oxygen atom),

[0029] * a group -OC(O)R 15 , with R 15representing an alkyl radical, a haloalkyl radical, an optionally substituted alkyl-aryl radical, an optionally substituted aryl radical, * a -C(O)OR group 16 , with R 16 representing an alkyl radical, a haloalkyl radical, an optionally substituted alkyl-aryl radical, an optionally substituted aryl radical,

[0030] * a phosphonic acid group (PO(OH)2),

[0031] * an ester group of phosphonic acid P(O)(OR) 17a )(GOLD 17b ), with R 17a representing a hydrogen atom or an alkyl radical, and R 17b representing an alkyl radical,

[0032] * a sulfonic acid group (SO3H),

[0033] * an ester group of sulfonic acid SO3R 18 , with R 18 representing an alkyl radical or a haloalkyl radical, and

[0034] * an amide group C(O)NR 19a R 19b , with R 19a and R 19b, independently of one another, representing a hydrogen atom or an alkyl radical, or together forming an alkyl radical.

[0035] 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).

[0036] 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.

[0037] 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 copolymer backbone. The greater their proportion relative to the monomers of formula (II), the higher the degradability of the copolymer. Thus, after degradation, the length of the fragments obtained is inversely proportional to the quantity of monomers of formula (I) integrated into the polymer backbone. In addition, the chemical groups at 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 synthesizable 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, the monomers of formula (II) are for the most part commercially available.

[0038] The monomer (I) of the invention is different from monomers known from the prior art such as thionolactide (or dithionolactide) which contains an -S(C=O)- unit. Dithionolactide therefore does not contain a C=S thiocarbonyl bond. This di(cyclic thioester) can be polymerized by non-radical ring opening, by base catalysis, to produce degradable poly(thioesters). This monomer cannot be copolymerized by a radical route with a comonomer (II) of the invention.

[0039] According to the present invention, the term "degradable polymer" means a polymer whose backbone comprises bonds that can be easily broken, in particular by chemical hydrolysis, aminolysis, or 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.

[0040] According to the invention, the expression "thionolactide monomers of formula (I)" includes thionolactide as such corresponding to the compound of formula (I) in which R 1 ,R 3 = H, and R 2 , R 4 = CH3; as well as any derivative of the aforementioned thionolactide corresponding to any of the compounds of formula (I) in which R 1 , R 2 , R 3 , R 4 are as defined in the invention.

[0041] Thionolactide monomers (I)

[0042] X is an oxygen atom or a sulfur atom, and preferably an oxygen atom. R 1 , R 2 , R 3 , and R 4, independently of each other, 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 CO2R 5 with R 5 representing an alkyl radical, a phosphonic acid radical (PO(OH)2), a phosphonic acid ester radical P(O)(OR 6a R 6b )2 with R 6a representing a hydrogen atom or an alkyl radical, and R 6b representing an alkyl radical, a sulfonic acid radical (SO3H), a sulfonic acid ester radical SO3R 7 with R 7 representing an alkyl radical or a haloalkyl radical, and an amide radical C(O)NR 8a R 8b , with R 8a and R 8b, independently of one another, representing a hydrogen atom or an alkyl radical, or together forming an alkyl radical.

[0043] The halogen atom as the R group 1 , R 2 , R 3 , and / or R 4 is preferably a fluorine atom.

[0044] The alkyl radical as the R group 1 , R 2 , R 3 , and / or R 4 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.

[0045] In the invention, the term "haloalkyl" means an alkyl radical comprising one or more halogen atoms, preferably chosen from chlorine and fluorine atoms.

[0046] The haloalkyl radical as the R group 1 , R 2 , R 3 , and / or R 4 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.

[0047] In the invention, the term "optionally substituted phenyl" means that the phenyl radical as group R 1 , R 2 , R 3 , and / or R 4may be substituted by one or more substituents such as halogen atoms, preferably selected from chlorine and fluorine atoms, alkyl groups, and haloalkyl groups. The haloalkyl group as a substituent of the phenyl radical preferably comprises from 1 to 3 carbon atoms. It is advantageously a trifluoromethyl group.

[0048] The alkyl group as a substituent of the phenyl radical preferably comprises from 1 to 3 carbon atoms. It is advantageously a methyl group.

[0049] The phenyl radical substituted by one or more halogen atoms is preferably a pentafluorinated phenyl radical -CeFs.

[0050] An alkyl-phenyl radical optionally substituted as the R group 1 , R 2 , R 3 , and / or R 4is 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 R groups 1 , R 2 , R 3 , and R 4 . 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.

[0051] A haloalkyl-phenyl radical optionally substituted as the R group 1 , R 2 , R 3 , and / or R 4is a radical comprising at least one haloalkyl 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 haloalkyl radical) covalent bond, the optionally substituted phenyl and haloalkyl radicals being as defined previously for the R groups 1 , R 2 , R 3 , and R 4 The haloalkyl radical is directly linked via a carbon atom to the thionolactide.

[0052] The alkyl radical as the R group 5 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.

[0053] The alkyl radical as the R group 6a or R 6b 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.

[0054] The alkyl radical as the R group 7 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.

[0055] The haloalkyl radical as the R group 7may 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.

[0056] The alkyl radical as the R group 8a or R 8b 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.

[0057] When the R groups 8a and R 8b together form an alkyl radical, we obtain a nitrogenous cycle in which R 8a and R8b together form an alkyl radical, in particular comprising 5 carbon atoms (piperidine ring).

[0058] Modulation of R groups 1 , R 2 , R 3 , and R 4 thionolactide (I) increases its reactivity towards non-activated monomers (II) such as vinyl ester monomers or towards activated monomers (II) such as acrylate, acrylamides, styrene, etc. monomers.

[0059] R 1 , R 2 , R 3 , and R 4, independently of one another, preferably 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, and particularly preferably a hydrogen atom, a halogen atom, an alkyl radical, a haloalkyl radical, and an optionally substituted phenyl radical. According to a preferred embodiment of the invention:

[0060] * R 1 = H or CH3,

[0061] * R2= H, CH3, C6H5, CF 3I C6F5, C6H4-CF3, F, CH2F, CH2CI, or C2H4-CI,

[0062] * R3= H or CH3,

[0063] * R4= H, CH3, C6H5, CF 3I C6F5, C6H4-CF 3I F, CH2F, CH2CI, or C2H4-CI.

[0064] The thionolactide of formula (I) is advantageously chosen from the following thionolactides:

[0065] (i) thionolactides in which R 2 and R 4 are as defined in the invention with the exclusion of hydrogen atoms, and particularly preferably are alkyl radicals,

[0066] (ii) thionolactides in which R 3 and R 4 are as defined in the invention with the exclusion of hydrogen atoms, and particularly preferably are alkyl radicals, and

[0067] (iii) thionolactides in which R 1 , R 2 , R 3 , or R 4 are hydrogen atoms.

[0068] In thionolactides (i), R 1 and R 3 are preferably hydrogen atoms.

[0069] In thionolactides (ii), R 1 and R 2 are preferably hydrogen atoms.

[0070] Thionolactides (i) and (ii) promote copolymerization with activated monomers (II).

[0071] Thionolactides (iii) promote copolymerization with unactivated monomers (II).

[0072] According to a particular embodiment of the invention, all of the R groups 1 and R 2 is identical to the set of groups R 3 and R 4 This leads to a “symmetrical” thionolactide (I) which is easier to prepare.

[0073] The thionolactides of formula (I) are advantageously chosen from the thionolactides of formulas (1-1) to (1-13) presented in the following table 1:

[0074]

[0075] TABLE 1

[0076] Among these thionolactides of formula (1-1) to (1-14), the thionolactides of formulas (1-1), (1-13), and (1-14) are particularly preferred.

[0077] Monomers (II) R 9 preferably represents a hydrogen atom.

[0078] R 10preferably represents a hydrogen atom.

[0079] R 11 preferably represents a hydrogen atom or an alkyl radical.

[0080] The alkyl radical as the R group 11 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 5 carbon atoms, and preferably from 1 to 3 carbon atoms. An alkyl radical is advantageously a methyl group.

[0081] The alkyl radical as the R group 12 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.

[0082] As examples of alkyl radicals as group R 12 , mention may be made of the 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.

[0083] The haloalkyl radical as the R group 12 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.

[0084] The aryl radical as the R group 12may 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.

[0085] As examples of aryl radical as R group 12 , we can in particular cite the phenyl, trityl, naphthalenyl, anthracenyl, and pyrenyl radicals. Among such radicals, the phenyl radical is particularly preferred.

[0086] The alkyl-aryl radical optionally substituted as group R 12 is a radical comprising at least one alkyl radical and at least one optionally substituted aryl radical which are linked directly 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 the group R 12The 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.

[0087] The alkyl substituent of the alkylimidazolium radical as the R group 12 preferably comprises from 1 to 16 carbon atoms, and particularly preferably from 1 to 5 carbon atoms. The alkylimidazolium radical as group R 12 preferably comprises a counterion selected from Br, BF4, and PFe'.

[0088] Formula group (III)

[0089] The alkyl radical as the R group 13 and / or R 14may be linear or branched, cyclic or non-cyclic. The alkyl radical is preferably linear. The alkyl radical may have from 1 to 22 carbon atoms, and preferably from 1 to 5 carbon atoms. Examples of alkyl radicals as the R group 13 and / or R 14 , we can mention the radicals 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, cyclohexylmethyl, adamantyl, and cyclohexyl.

[0090] The aryl radical as the R group 13 and / or R 14 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.

[0091] As examples of aryl radical as R group 13 and / or R 14 , we can in particular cite the phenyl, trityl, naphthalenyl, anthracenyl, and pyrenyl radicals. Among such radicals, the phenyl radical is particularly preferred.

[0092] The alkyl-aryl radical optionally substituted as group R 13 and / or R 14 is a radical comprising at least one alkyl radical and at least one optionally substituted aryl radical which are linked directly 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 the R groups 13 and R 14 . The alkyl radical is directly linked via a carbon atom to the nitrogen atom of formula (III) for R 13 and to the carboxyl function of formula (III) for R 14An optionally substituted alkyl-aryl radical is advantageously a benzyl or pentafluorobenzyl radical.

[0093] When R 13 and R 14 , together with the nitrogen and carbon atoms of the group of formula (III) to which they are linked, form a heterocarbon ring, which may in particular be a pyrrolidone, piperidone, or caprolactam ring.

[0094] According to a preferred embodiment of the invention, R 13 and R 14 , identical or different, represent a hydrogen atom, an alkyl radical, or R 13 and R 14 together with the nitrogen and carbon atoms of the group of formula (III) to which they are bound, form a heterocarbon ring comprising from 4 to 7 carbon atoms (including the carbon atom bearing the oxygen atom).

[0095] According to a particularly preferred embodiment, R 13 and R 14are 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.

[0096] Group -OC(O)R 15

[0097] The alkyl radical as the R group 15 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.

[0098] As examples of alkyl radicals as group R 15, we can mention the radicals 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, cyclohexylmethyl, adamantyl, and cyclohexyl.

[0099] The aryl radical as the R group 15 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.

[0100] As examples of aryl radical as R group 15 , we can in particular cite the phenyl, trityl, naphthalenyl, anthracenyl, and pyrenyl radicals. Among such radicals, the phenyl radical is particularly preferred.

[0101] The alkyl-aryl radical optionally substituted as group R 15 is a radical comprising at least one alkyl radical and at least one optionally substituted aryl radical which are linked directly 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 the group R 15 . 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.

[0102] The haloalkyl radical as the R group 15 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. R 15preferably represents an alkyl or haloalkyl radical, and particularly preferably an alkyl radical such as a methyl or t-butyl radical.

[0103] Group -C(O)OR 16

[0104] The alkyl radical as the R group 16 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.

[0105] As examples of alkyl radicals as group R 16 , the radicals 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, isobornyl, cyclohexylmethyl, adamantyl, and cyclohexyl may be mentioned.

[0106] The aryl radical as the R group 16 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.

[0107] As examples of aryl radical as R group 16 , we can in particular cite the phenyl, trityl, naphthalenyl, anthracenyl, and pyrenyl radicals. Among such radicals, the phenyl radical is particularly preferred.

[0108] The alkyl-aryl radical optionally substituted as group R 16is a radical comprising at least one alkyl radical and at least one optionally substituted aryl radical which are linked directly 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 the group R 16 . 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.

[0109] The haloalkyl radical as the R group 16 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. R 16preferably represents an alkyl radical, and particularly preferably a methyl or t-butyl radical.

[0110] The alkyl radical as the R group 17a or R 17b 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.

[0111] The alkyl radical as the R group 18 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.

[0112] The haloalkyl radical as the R group 18 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.

[0113] The alkyl radical as the R group 19a or R 19b 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.

[0114] When the R groups 19a and R 19btogether form an alkyl radical, we obtain a nitrogenous cycle in which R 19a and R 19b together form an alkyl radical, in particular comprising 5 carbon atoms (piperidine ring).

[0115] According to a particular embodiment, the monomer of formula (II) is chosen from:

[0116] * vinyl ester type monomers represented by the following formula (11-1): in which R 15 is as defined in the invention,

[0117] * the a-olefin type monomers represented by the following formula (II-2):

[0118] (11-2) in which R 11 represents a hydrogen atom or an alkyl radical as defined in the invention, and R 12 represents an alkyl radical or an optionally substituted aryl radical as defined in the invention,

[0119] * N-vinyl type monomers represented by the following formula (111-1): in which R 13 and R 14 are as defined in the invention,

[0120] * acrylate and alkacrylate monomers represented by the following formula (II-3): in which R 11 represents a hydrogen atom or an alkyl radical as defined in the invention, and R 16 represents an alkyl radical as defined in the invention.

[0121] Among the monomers of formula (11-1), we can cite vinyl acetate, vinyl pivalate, vinyl trifluoroacetate, vinyl chloroacetate, vinyl propionate, vinyl butyrate, vinyl neodecanoate (R 15 = C9H19, mixture of isomers), and vinyl trifluorobutyrate. Among these monomers of formula (11-1), vinyl acetate and vinyl pivalate are particularly preferred.

[0122] Among the monomers of formula (II-2), mention may be made of ethylene and octene. Ethylene is particularly preferred.

[0123] Among the monomers of formula (111-1), mention may in particular be made of acyclic N-vinyl monomers such as N-vinylformamide, N-vinylacetamide and N-methyl-N-vinylacetamide, as well as cyclic N-vinyl monomers, (when R 13 and R 14 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.

[0124] 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.

[0125] 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. When the proportion of monomers of formula (I) is greater than 30% by number, the radical polymerization process by ring opening is impaired, in particular slowed down.

[0126] 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.

[0127] 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).

[0128] Among the organic peroxides and hydroperoxides, mention may be made in particular 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.

[0129] Among the azo derivatives, mention may be made in particular 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-[1,1 bis-(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) and 1,T-azobis-(cyclohexanecarbonitrile) are particularly preferred.

[0130] Redox systems are for example chosen from systems comprising combinations such as:

[0131] - 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 sodium formaldehyde sulfoxylate, and a reducing sugar,

[0132] - 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

[0133] - mixtures of an alkali metal persulfate with an arylphosphinic acid, such as benzenephosphonic acid and the like, and a reducing sugar.

[0134] Among such redox systems, particularly preferred are combinations of ammonium persulfate and sodium formaldehyde sulfoxylate, and tert-butyl hydroperoxide and ascorbic acid.

[0135] It is also possible to use a photochemical initiator, in the ultraviolet (UV) or visible range. Among the initiators that can be used in the UV range, we can notably mention 2,2-dimethoxy-2-phenylacetophenone, benzophenone / amine or benzophenone / alcohol pairs. Among the initiators that can be used in the visible range, 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 range.

[0136] 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%.

[0137] 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 precipitating route, or in dispersion, emulsion or suspension.

[0138] According to a preferred embodiment of the invention, water, hydroalcoholic mixtures or organic solvents are used as reaction medium. Organic solvents are preferred.

[0139] The total amount of polymerizable material in the reaction medium (total amount of monomers of formula (I) and formula (II)) may 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 amount may vary from approximately 10% to 90% by mass relative to the total mass of the reaction medium, preferably from approximately 20% to 80% by mass, and even more preferably from approximately 30% to 60% relative to the total mass of the reaction medium.

[0140] The polymerization step of the process according to the invention can be carried out at a temperature ranging from approximately 5 to 150°C, 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 approximately 20 to 130°C, and even more preferably from approximately 40 to 110°C.

[0141] The duration of the polymerization step generally varies from approximately 1 to 12 hours, and even more preferably from approximately 2 to 8 hours.

[0142] 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 methods 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), atom transfer polymerization (ATRP), iodine transfer polymerization (ITP), reversible chain transfer-catalyzed radical polymerization (RCTP), polymerization in the presence of organotellurium compounds (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.,

[0143] The process of the invention thus makes it possible to produce a copolymer having at least thioester bonds which are easily degradable.

[0144] 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 orthodithioester and / or thioacetal bonds. These cyclic monomer units (I) having orthodithioester and / or thioacetal bonds have the advantage of being sensitive to chemical attack and therefore potentially degradable.

[0145] 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. 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:

[0146] (i) at least one cyclic monomer chosen from the thionolactides of the following formula (I): in which:

[0147] - X is an oxygen atom or a sulfur atom;

[0148] - R 1 , R 2 , R 3 , and R 4, independently of each other, 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 CO2R 5 with R 5 representing an alkyl radical, a phosphonic acid radical (PO(OH)2), a phosphonic acid ester radical P(O)(OR 6a )(GOLD 6b ) with R 6a representing a hydrogen atom or an alkyl radical, and R 6b representing an alkyl radical, a sulfonic acid radical (SO3H), a sulfonic acid ester radical SO3R 7 with R 7 representing an alkyl radical or a haloalkyl radical, and an amide radical C(O)NR 8a R 8b , with R 8a and R 8b, 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): in which:

[0149] - R 9 represents a hydrogen atom, or a fluorine atom;

[0150] - R 10 represents a hydrogen atom, or a fluorine atom;

[0151] - R 11 represents a hydrogen atom, an alkyl radical, a fluorine atom, or a chlorine atom;

[0152] - R 12 represents a hydrogen atom, or a group chosen from the following groups:

[0153] * an alkyl radical,

[0154] * a haloalkyl radical,

[0155] * an optionally substituted aryl radical,

[0156] * an optionally substituted alkyl-aryl radical,

[0157] * an imidazolyl group,

[0158] * an alkylimidazolium group,

[0159] * a carbazoyl group,

[0160] * a group of formula (III) following: 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 R 13 and R 14 , 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 R 13 and R 14 together with the nitrogen and carbon atoms of the group of formula (III) to which they are bound, form a heterocarbon ring comprising from 4 to 7 carbon atoms (including the carbon atom bearing the oxygen atom),

[0161] * a group -OC(O)R 15 , with R 15representing an alkyl radical, a haloalkyl radical, an optionally substituted alkyl-aryl radical, an optionally substituted aryl radical,

[0162] * a group -C(O)OR 16 , with R 16 representing an alkyl radical, a haloalkyl radical, an optionally substituted alkyl-aryl radical, an optionally substituted aryl radical,

[0163] * a phosphonic acid group (PO(OH)2),

[0164] * an ester group of phosphonic acid P(O)(OR) 17a )(GOLD 17b ), with R 17a representing a hydrogen atom or an alkyl radical, and R 17b representing an alkyl radical,

[0165] * a sulfonic acid group (SO3H),

[0166] * an ester group of sulfonic acid SO3R 18 , with R 18 representing an alkyl radical or a haloalkyl radical, and

[0167] * an amide group C(O)NR 19a R 19b , with R19a and R 19b , independently of one another, representing a hydrogen atom or an alkyl radical, or together forming an alkyl radical, in the presence of a radical polymerization initiator.

[0168] The preferences indicated above with reference to the first subject of the invention concerning the monomers of formulae (I) and (II), also apply to the second subject of the invention.

[0169] According to a particular and preferred embodiment of the invention, said copolymer results from the polymerization of thionolactide (1-1) and vinyl acetate, styrene, tert-butyl acrylate, methyl methacrylate, or vinyl pivalate.

[0170] According to a preferred embodiment of the second subject of the invention, the copolymer, preferably degradable, is a random copolymer.

[0171] 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.

[0172] 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.

[0173] The rate 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.

[0174] The copolymer may further comprise orthodithioester and / or thioacetal linkages which are also degradable.

[0175] 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.

[0176] 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.

[0177] For the copolymers of the invention which would have only 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.

[0178] The invention also has as a third subject the use of at least one thionolactide corresponding to formula (I) as defined in the first subject of the invention as precursor monomer in a radical polymerization.

[0179] The radical polymerization is as defined in the first subject of the invention.

[0180] Certain thionolactides corresponding to formula (I) are novel in themselves and constitute a fourth subject of the invention.

[0181] 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 (I'): in which:

[0182] - X, R 1 , R 2 , R 3 , and R 4 are as defined in the first subject of the invention,

[0183] - excluding thionolactides (I-1) and (I-2) as defined in the invention.

[0184] Preferably, the thionolactide of formula (I') is chosen from the thionolactides of formulas (I-3) to (I-14) as described in the invention.

[0185] The lactide precursors of the thionolactides of formula (I) or (I') as described in the invention can be obtained by dimerization of corresponding alpha-hydroxy acids or, in the case of compounds (1-13) and (1-14), by reaction of alpha-hydroxyisobutyric acid with chloroacetyl chloride or chloropropyl. The single or double thionation of the lactides can be carried out in the presence of P4S10 and hexamethyldisiloxane (HMDSO).

[0186] Brief description of the drawings

[0187] The accompanying drawings illustrate the invention:

[0188] Figure 1 illustrates the chemical degradation of a CP2 polymer according to the invention.

[0189] Figure 2 illustrates the chemical degradation of a CP6 polymer according to the invention.

[0190] Figure 3 illustrates the crystal structure of the compound (1-13) used in a process according to the invention.

[0191] Figure 4 illustrates the chemical degradation of a CP8 polymer according to the invention.

[0192] Figure 5 illustrates the crystal structure of the compound (1-14) used in a process according to the invention.

[0193] Figure 6 illustrates the chemical degradation of a CP10 polymer in accordance with the invention. Other characteristics and advantages of the present invention will appear in the light of the description of examples presented below to which the invention is however not limited.

[0194] Examples

[0195] Size exclusion chromatography analyses were performed with a setup equipped with two Shodex columns (KF-805 + KF-804 + KF-802.5), a refractometric detector and a light scattering detector, for analysis in tetrahydrofuran (THF) at 35°C and a flow rate of 1 ml / min.

[0196] Example 1: Synthesis of a degradable copolymer CP1 based on styrene and thionolactide of formula (1-1) according to the process of the invention

[0197] 1.1 First step: synthesis of thionolactide of formula (1-1)

[0198] P4S10 (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 into a two-necked flask topped with a condenser. The resulting mixture was heated at reflux for 48 hours. Then, the reaction medium was cooled to room temperature, filtered through 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). Thionolactide was recrystallized four times to obtain crystals with a yield of 33% (1.8 g). The crystals obtained were sublimated before their use in polymerization at 60°C and at a pressure of 10' 2 mbar.

[0199] 1 H NMR (CDCI3, 300 MHz) ô (ppm): 5.06 (q, 1 H), 4.98 (q, 1 H), 1.79 (d, 3H), 1.76 (d, 3H).

[0200] 13C NMR (CDCI3, 126 MHz) δ (ppm): 211.4, 167.5, 78.4, 75.1, 19.3, 15.5.

[0201] 1.2 Second step: synthesis of the copolymer poly(styrene-co-thionolactide) CP1

[0202] 6 mg (0.025 mmol) of azobis(cyanocyclohexane) (VAZO-88), 0.08 g (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 were mixed to form a solution. Thionolactide (monomer of formula (1-1 )) represents 10% (by mole) relative to styrene (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.

[0203] Conversion to monomer was determined by hydrogen nuclear magnetic resonance (NMR 1 H). 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 (1-1 ) 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: 5 1 j 49 (i - 1) (xh)

[0204] Conversion (I — 1) = 1 — l - IXO h)

[0205] Conversion to monomer, determined by hydrogen nuclear magnetic resonance (NMR 1H), 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 copolymer CP1 were measured by size exclusion chromatography (eluent: tetrahydrofuran THF) with a PMMA-based calibration curve: Mn = 13200 g / mol; Mw / Mn = 2.3.

[0206] 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

[0207] 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. The conversion to monomer, determined by hydrogen nuclear magnetic resonance (NMR 1H), as explained in Example 1 was 34% for thionolactide (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 poly(tert-butyl acrylate-co-thionolactide) copolymer CP2 were measured by size exclusion chromatography (eluent: THF) with a PMMA-based calibration curve: Mn = 8000 g / mol; Mw / Mn = 1.7.

[0208] 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

[0209] 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 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.

[0210] Conversion to monomer, determined by hydrogen nuclear magnetic resonance (NMR 1H), 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.

[0211] 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

[0212] 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 to 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.

[0213] Conversion to monomer, determined by hydrogen nuclear magnetic resonance (NMR 1H), 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.

[0214] Example 5: Chemical degradation of a degradable copolymer CP2 based on tert-butyl acrylate and thionolactide of formula (1-1)

[0215] 10 mg of the CP2 copolymer of Example 2 was diluted in 1 ml of THF and 1 ml of a bleach solution (aqueous NaOCI 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.

[0216] Figure 1 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, Figure 1 a), of the residue obtained after contacting CP2 with bleach (Mn = 2100 g / mol, Mw / Mn = 1.5, Figure 1 b), and of CP2 diluted in THF and left at room temperature for 30 days (Mn = 6400 g / mol, Mw / Mn = 2.0, Figure 1 c).

[0217] 11 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.

[0218] 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

[0219] 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 to 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).

[0220] Conversion to monomer, determined by hydrogen nuclear magnetic resonance (NMR 1H), 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 poly(n-butyl acrylate-co-thionolactide) copolymer CP5 were measured by size exclusion chromatography (eluent: THF) with a PMMA-based calibration curve: Mn = 98000 g / mol; Mw / Mn = 1.7.

[0221] Example 7: Synthesis of a degradable copolymer CP6 based on tert-butyl acrylate and dithionolactide of formula (I-2) according to the process of the invention

[0222] 7.1 First step: synthesis of dithionolactide of formula (I-2)

[0223] In a two-necked flask topped with a condenser, P4S10 (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 through 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). Dithionolactide (I-2) was recrystallized four times to obtain crystals with a yield of 2% (0.1 g). The crystals obtained were sublimated before their use in polymerization at 60°C and at a pressure of 10' 2 mbar.

[0224] 1 H NMR (CDC, 300 MHz) δ (ppm): 5.05 (q, 6.3 Hz, 2H), 1.8 (d, 6.3 Hz, 6H).

[0225] 13C NMR (CDCI3, 126 MHz) δ (ppm): 211.2, 78.6, 19.5.

[0226] 7.2 Second step: synthesis of the degradable copolymer CP6 based on tert-butyl acrylate and dithionolactide of formula (I-2) according to the process of the invention

[0227] 5.3 mg (0.022 mmol) of azobis(cyanocyclohexane) (VAZO-88), 0.04 g (0.22 mmol) of dithionolactide (I-2) obtained in Example 7.1, 0.552 g (4.3 mmol) of tert-butyl acrylate, and 10 mg of naphthalene as an internal standard were mixed to form a solution. Dithionolactide (monomer of formula (I-2)) represents 5% (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 dithionolactide (I-2) after 5 h of reaction.

[0228] Conversion to monomer was determined by hydrogen nuclear magnetic resonance (NMR 1H). 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 5.0 - 5.1 ppm which corresponds to two hydrogen atoms of dithionolactide (I-2) and compared with the result of the integral at a reaction time equal to 0 hours. The conversion of dithionolactide (I-2) after a reaction time of X hours can thus be determined according to the following equation 2:

[0229] Conversion to monomer, determined by hydrogen nuclear magnetic resonance (NMR 1H) was 100% for dithionolactide (I-2) and 98% for tert-butyl acrylate. Residual monomers were evaporated and the number-average molar mass (Mn) and the polydispersity index (Mw / Mn) of the poly(tert-butyl acrylate-co-thionolactide) copolymer CP6 were measured by size exclusion chromatography (eluent: THF) with a PMMA-based calibration curve: Mn = 28300 g / mol; Mw / Mn = 2.5.

[0230] Example 8: Chemical degradation of a degradable copolymer CP6 based on tert-butyl acrylate and dithionolactide of formula (1-2)

[0231] 10 mg of the CP6 copolymer of Example 7 was diluted in 1 ml of THF and 1 ml of a bleach solution (aqueous NaOCI 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.

[0232] 10 mg of the CP6 copolymer of Example 7 was diluted in 1 ml of THF and 1 ml of isopropylamine solution was added. The resulting mixture was kept stirring in a sealed tube for 30 days at room temperature. The solvent and isopropylamine were evaporated under reduced pressure, and then the residue was dissolved in THF and analyzed by size exclusion chromatography.

[0233] Figure 2 shows the behavior of CP6 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 and isopropyl amine (Mn = 28300 g / mol; Mw / Mn = 2.5. Figure 2a), of the residue obtained after contacting CP6 with bleach (Mn = 7700 g / mol, Mw / Mn = 3.5, Figure 2b), and of the residue obtained after contacting CP6 with isopropylamine (Mn = 8200 g / mol, Mw / Mn = 2.8, Figure 2c).

[0234] It appears that after degradation of the CP6 copolymer either by bleach or by isopropylamine, the molar mass distribution is strongly shifted towards 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.

[0235] Example 9: Synthesis of a degradable copolymer CP7 based on methyl methacrylate and dithionolactide of formula (I-2) according to the process of the invention.

[0236] 5.5 mg (0.023 mmol) of azobis(cyanocyclohexane) (VAZO-88), 0.04 g (0.23 mmol) of dithionolactide (I-2) obtained in Example 7.1, 0.43 g (4.3 mmol) of methyl methacrylate, and 10 mg of naphthalene as an internal standard were mixed to form a solution. Dithionolactide (monomer of formula (I-2)) represents 5% (by mole) relative to methyl methacrylate (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 dithionolactide (I-2) after 5 h of reaction.

[0237] Conversion to monomer, determined by hydrogen nuclear magnetic resonance (NMR 1 H), as explained in Example 7.2, was 20% for dithionolactide (I-2) and 80% for methyl methacrylate. The residual monomers were evaporated and the number-average molar mass (Mn) and the polydispersity index (Mw / Mn) of the poly(methyl methacrylate-co-dithionolactide) copolymer CP7 were measured by size exclusion chromatography (eluent: THF) with a PMMA-based calibration curve: Mn = 15000 g / mol; Mw / Mn = 2.7.

[0238] Example 10: Synthesis of thionolactide of formula (I-3)

[0239] In a two-necked flask topped with a condenser, P4S10 (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) to obtain a yield of 20% (1.1 g).

[0240] 1 H NMR (CDCI3, 300 MHz) δ (ppm): 5.2 (s, 4H).

[0241] 13 C NMR (CDCI3, 126 MHz) ô (ppm): 206, 165, 78, 73.

[0242] Example 11: Synthesis of a degradable copolymer CP8 based on tert-butyl acrylate and thionolactide of formula (1-13) according to the process of the invention

[0243] 11.1 First step: Synthesis of 3,3-dimethylglycolide 9.2 g (88.5 mmol) of alpha-hydroxyisobutyric acid, 10 g of chloroacetyl chloride (88.5 mmol) in 20 ml of anhydrous acetonitrile were introduced into a two-necked flask topped with a condenser. 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 17.9 g of triethylamine (177 mmol) were added dropwise. The resulting solution was then heated at 80°C for 6 hours. After filtration, the product was obtained by evaporation of the solvent with a yield of 40% (5.1 g).

[0244] 1 H NMR (CDCh, 300 MHz): δ (ppm): 1.67 (s, 6H); 5.01 (s, 2H).

[0245] 13C NMR (CDCh, 126 MHz) ô (ppm): 167, 164, 75, 73, 24.

[0246] 11.2 Second step: synthesis of thionolactide 3,3-dimethylthioglycolide of formula (1-13)

[0247] In a two-necked flask topped with a condenser, P4S10 (8.7 mmol, 3.9 g), 2,2-dimethylglycolide from Example 11.1 (34.7 mmol, 5 g), hexamethyldisiloxane (HMDSO) (58.0 mmol, 9.4 g) and 50 ml of anhydrous toluene were introduced, the whole being inerted by bubbling argon. The resulting mixture was heated at reflux for 24 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) to obtain a yield of 20% (1.8 g).

[0248] 1H NMR (CDCh, 300 MHz): 5.2 ppm (s, 2H), 1.76 ppm (s, 6H).

[0249] 13 C NMR (CDCh, 126 MHz): 206.2, 167.7, 82.5, 73.8, 25.2.

[0250] Figure 3 illustrates the crystal structure of thionolactide (1-13).

[0251] 11.3 Third step: synthesis of the degradable copolymer CP8 based on tert-butyl acrylate and thionolactide of formula (1-13) according to the process of the invention

[0252] 5.3 mg (0.022 mmol) of azobis(cyanocyclohexane) (VAZO-88), 0.07 g (0.44 mmol) of thionolactide (1-13) obtained in Example 11.2, 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 (1-13)) 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 (1-13) after 5 h of reaction.

[0253] Conversion to monomer was determined by hydrogen nuclear magnetic resonance (NMR 1H). 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 5.3-5.1 ppm which corresponds to two hydrogen atoms of thionolactide (1-13) and compared with the result of the integral at a reaction time equal to 0 hours. The conversion of thionolactide (1-13) after a reaction time of X hours can thus be determined according to the following equation 3:

[0254] Conversion to monomer, determined by hydrogen nuclear magnetic resonance (NMR 1H) was 44% for thionolactide (1-13) and 82% for tert-butyl acrylate. Residual monomers were evaporated and the number-average molar mass (Mn) and the polydispersity index (Mw / Mn) of the poly(tert-butyl acrylate-co-thionolactide) copolymer CP8 were measured by size exclusion chromatography (eluent: THF) with a PMMA-based calibration curve: Mn = 13800 g / mol; Mw / Mn = 2.4.

[0255] Example 12: Chemical degradation of a degradable copolymer CP8 based on tert-butyl acrylate and thionolactide of formula (1-13)

[0256] 10 mg of the CP8 copolymer of Example 11.3 was diluted in 1 ml of THF and 1 ml of a bleach solution (aqueous NaOCI 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. Figure 4 shows the behavior of CP8 before degradation 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) (CP8 in THF, Mn = 13800 g / mol; Mw / Mn = 2.4, figure 4a), and of the residue obtained after contacting CP2 with bleach (Mn = 3300 g / mol, Mw / Mn = 1.6, figure 4b).

[0257] It appears that after degradation of the CP8 copolymer by bleach, the molar mass distribution is strongly shifted towards 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.

[0258] Example 13: Synthesis of a degradable copolymer CP9 based on methyl methacrylate and thionolactide of formula (1-13) according to the process of the invention

[0259] 6.1 mg (0.025 mmol) of azobis(cyanocyclohexane) (VAZO-88), 0.08 g (0.5 mmol) of thionolactide (1-13) obtained in Example 11.2, 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 (1-13)) represents 10% (by mole) relative to methyl methacrylate (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 (1-13) after 5 h of reaction.

[0260] Conversion to monomer, determined by hydrogen nuclear magnetic resonance (NMR 1H), as explained in Example 11.2 was 25% for thionolactide (1-13) and 90% for methyl methacrylate. The residual monomers were evaporated and the number-average molar mass (Mn) and the polydispersity index (Mw / Mn) of the poly(methyl methacrylate-co-thionolactide) copolymer CP9 were measured by size exclusion chromatography (eluent: THF) with a PMMA-based calibration curve: Mn = 13900 g / mol; Mw / Mn = 2.0.

[0261] Example 14: Synthesis of a degradable copolymer CP10 based on tert-butyl acrylate and thionolactide of formula (1-14) according to the process of the invention

[0262] 14.1 First step: synthesis of 3,3,6-trimethylglycolide 8.2 g (78.7 mmol) of alpha-hydroxyisobutyric acid and 10 g of chloropropyl chloride (78.7 mmol) in 20 ml of anhydrous acetonitrile were introduced into a two-necked flask topped with a condenser. 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 15.9 g of triethylamine (157.5 mmol) were added dropwise. The resulting solution was then heated at 80°C for 6 hours. After filtration, the product was obtained by evaporation of the solvent with a yield of 40% (4.4 g).

[0263] 1 H NMR (CDCh, 300 MHz) δ (ppm): 1.68 (m, 9H); 5.09 (q, 7.2 Hz, 1 H).

[0264] 13 C NMR (CDCh, 126 MHz) δ (ppm): 168.8, 166.8, 80.7, 73.1, 26.4, 25.4, 17.6.

[0265] 14.2 Second step: synthesis of thionolactide 3,3,6-trimethylthioglycolide of formula (1-14)

[0266] In a two-necked flask topped with a condenser, P4S10 (4.7 mmol, 2.1 g), 2,2-dimethylglycolide from Example 14.1 (19 mmol, 3 g), hexamethyldisiloxane (HMDSO) (31.7 mmol, 5.1 g) and 50 ml of anhydrous toluene were introduced, the whole being inerted by bubbling argon. The resulting mixture was heated at reflux for 24 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: 20% ethyl ether / 80% petroleum ether) to obtain a yield of 25% (0.8 g).

[0267] 1H NMR (CDCh, 300 MHz) ô (ppm): 5.2 (q, 6.6 Hz, 1 H), 1 .87 (d, 6.6 Hz, 3H), 1 .79 (s, 6H).

[0268] 13 C NMR (CDCh, 126 MHz) (ppm): 211 .4, 169.0, 83.2, 79.6, 24.7, 21 .5.

[0269] Figure 5 illustrates the crystal structure of thiolactide (1–14).

[0270] 14.3 Third step: synthesis of the degradable copolymer CP10 based on tert-butyl acrylate and thionolactide of formula (1-14) according to the process of the invention 5 mg (0.02 mmol) of azobis(cyanocyclohexane) (VAZO-88), 0.07 g (0.40 mmol) of thionolactide (1-14) obtained in Example 14.2, 0.464 g (3.6 mmol) of tert-butyl acrylate, and 10 mg of naphthalene as an internal standard were mixed to form a solution. The thionolactide (monomer of formula (1-14)) represents 10% (in moles) relative to the tert-butyl acrylate (monomer of formula (II)). The solution was transferred into a Carius tube, which was vacuum sealed 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 (1-14) after 5 hours of reaction.

[0271] Conversion to monomer was determined by hydrogen nuclear magnetic resonance (NMR 1 H). 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 5.1-4.9 ppm which corresponds to two hydrogen atoms of thionolactide (1-14) and compared with the result of the integral at a reaction time equal to 0 hours. The conversion of thionolactide (1-14) after a reaction time of X hours can thus be determined according to the following equation 4: 5 1

[0272] 49(I - 14) (X h)

[0273] Conversion (I — 14) = 1 — 01 - 14) (O h)

[0274] Conversion to monomer, determined by hydrogen nuclear magnetic resonance (NMR 1H) was 26% for thionolactide (1-14) and 52% for tert-butyl acrylate. 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) CP10 were measured by size exclusion chromatography (eluent: THF) with a PMMA-based calibration curve: Mn = 13500 g / mol; Mw / Mn = 4.2.

[0275] Example 15: Chemical degradation of a degradable copolymer CP10 based on tert-butyl acrylate and thionolactide of formula (1-14)

[0276] 10 mg of the CP10 copolymer of Example 14.3 was diluted in 1 ml of THF and 1 ml of a bleach solution (aqueous NaOCI 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.

[0277] Figure 6 shows the behavior of CP10 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 (CP10 in THF, Mn = 13500 g / mol; Mw / Mn = 3.8, Figure 6a), and of the residue obtained after contacting CP10 with bleach (Mn = 5700 g / mol, Mw / Mn = 1.9, Figure 6b).

[0278] It appears that after degradation of the CP10 copolymer by bleach, the molar mass distribution is strongly 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.

[0279] Example 16: Synthesis of a degradable copolymer CP11 based on methyl methacrylate and thionolactide of formula (1-14) according to the process of the invention

[0280] 5.6 mg (0.023 mmol) of azobis(cyanocyclohexane) (VAZO-88), 0.08 g (0.46 mmol) of thionolactide (1-14) obtained in Example 14.2, 0.414 g (4.6 mmol) of methyl methacrylate, and 10 mg of naphthalene as an internal standard were mixed to form a solution. Thionolactide (monomer of formula (1-14)) represents 10% (by mole) relative to methyl methacrylate (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 (1-14) after 5 h of reaction.

[0281] Conversion to monomer, determined by hydrogen nuclear magnetic resonance (NMR 1H), as explained in Example 14.3 was 15% for thionolactide (1-14) and 28% 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 CP11 were measured by size exclusion chromatography (eluent: THF) with a PMMA-based calibration curve: Mn = 2400 g / mol; Mw / Mn = 1.4. Example 17: Synthesis of a degradable copolymer CP12 based on styrene and thionolactide of formula (1-14) according to the process of the invention

[0282] 5 mg (0.020 mmol) of azobis(cyanocyclohexane) (VAZO-88), 0.07 g (0.4 mmol) of thionolactide (1-14) obtained in Example 14.2, 0.377 g (3.6 mmol) of styrene, and 10 mg of naphthalene as an internal standard were mixed to form a solution. Thionolactide (monomer of formula (1-14)) represents 10% (by mole) relative to styrene (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 (1-14) after 5 h of reaction.

[0283] Conversion to monomer, determined by hydrogen nuclear magnetic resonance (NMR 1H), as explained in Example 14.3, was 26% for thionolactide (1-14) and 46% for styrene. The residual monomers were evaporated and the number-average molar mass (Mn) and the polydispersity index (Mw / Mn) of the copolymer CP12 were measured by size exclusion chromatography (eluent: tetrahydrofuran THF) with a PMMA-based calibration curve: Mn = 3700 g / mol; Mw / Mn = 3.2.

Claims

Demands 1. A process for preparing at least one copolymer, preferably degradable, said process comprising at least one ring-opening radical polymerization step of at least one cyclic monomer with at least one monomer having an 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 the following formula (I): (in which: - X is an oxygen atom or a sulfur atom; - R 1 , R 2 , R 3 , and R 4Independently of each other, they represent a hydrogen atom, a halogen atom, a group chosen from an alkyl radical, a haloalkyl radical, a possibly substituted phenyl radical, a cyano group, a possibly substituted alkyl-phenyl radical, a possibly substituted haloalkyl-phenyl radical, a carboxylic acid radical, and a CO2R ester radical. 5 with R 5 representing an alkyl radical, a phosphonic acid radical, a phosphonic acid ester radical P(O)(OR 6a )(GOLD 6b ) with R 6a representing a hydrogen atom or an alkyl radical, and R 6b representing an alkyl radical, a sulfonic acid radical, a sulfonic acid ester radical SO3R 7 with R 7 representing an alkyl radical or a haloalkyl radical, and an amide radical C(O)NR 8a R 8b , with R 8a and R 8b, independently of each other, representing a hydrogen atom or an alkyl radical, or together forming an alkyl radical; and in that: (ii) the monomer having an ethylenic unsaturation is chosen from the monomers of the following formula (II): (I in which: - R 9 represents a hydrogen atom, or a fluorine atom; - R 10 represents a hydrogen atom, or a fluorine atom; - R 11 represents a hydrogen atom, an alkyl radical, a fluorine atom, or a chlorine atom; - R 12 represents a hydrogen atom, or a group chosen from the following groups: * an alkyl radical, * a haloalkyl radical, * an aryl radical, possibly substituted, * a possibly substituted alkyl-aryl radical, * an imidazolyl group, * an alkylimidazolium group, * a carbazoyl group, * a group of the following formula (III): in which the asterisk (*) represents the point of attachment of the group of formula (III) to the carbon atom of the compound of formula (II), and R 13 and R 14 , identical or different, represent a hydrogen atom, an alkyl radical, a possibly substituted alkyl-aryl radical, a possibly substituted aryl radical, a glycidyl group, or R 13 and R 14 together with the nitrogen and carbon atoms of the group of formula (III) to which they are bonded, form a heterocarbon ring comprising 4 to 7 carbon atoms, * a group -OC(O)R 15 , with R 15 representing an alkyl radical, a haloalkyl radical, a possibly substituted alkyl-aryl radical, a possibly substituted aryl radical, * a group -C(O)OR 16 , with R 16representing an alkyl radical, a haloalkyl radical, a possibly substituted alkyl-aryl radical, a possibly substituted aryl radical, * a phosphonic acid group, * an ester group of phosphonic acid P(O)(OR 17a )(GOLD 17b ), with R 17a representing a hydrogen atom or an alkyl radical, and R 17b representing an alkyl radical, * a sulfonic acid group, * an ester group of sulfonic acid SO3R 18 , with R 18 representing an alkyl radical or a haloalkyl radical, and * an amide group C(O)NR 19a R 19b , with R 19a and R 19b independently of each other, representing a hydrogen atom or an alkyl radical, or together forming an alkyl radical.

2. A method according to claim 1, characterized in that R 1 , R 2 , R 3 , and R 4, independently of each other, represent a hydrogen atom, a halogen atom, a group chosen from an alkyl radical, a haloalkyl radical, a possibly substituted phenyl radical, a possibly substituted alkyl-phenyl radical, and a possibly substituted haloalkyl-phenyl radical.

3. A method according to claim 1 or 2, characterized in that: * R 1 = H or CH3, * R2 = H, CH3, C6H5, CF 3I C6F5, C6H4-CF3, F, CH2F, CH2CI, or C2H4-CI, * R3 = H or CH3 * R4 = H, CH3, C6H5, CF 3I C6F5, C6H4-CF3, F, CH2F, CH2CI, or C2H4-CI.

4. A method according to any one of the preceding claims, characterized in that the thionolactide of formula (I) is selected from the following thionolactides: (i) thionolactides in which R 2 and R 4 are as defined in claim 1, excluding hydrogen atoms, (ii) thionolactides in which R 3 and R 4 are such as defined in claim 1 excluding hydrogen atoms, and (iii) the thionolactides in which R 1 , R 2 , R 3 , or R 4 are hydrogen atoms.

5. A method according to any one of the preceding claims, characterized in that the thionolactides of formula (I) are selected from the thionolactides of formulas (1-1) to (1-13) shown in the following Table 1: TABLE 1 6. A method according to any one of the preceding claims, characterized in that R 9 represents a hydrogen atom, R 10 represents a hydrogen atom, and R 11 represents a hydrogen atom or an alkyl radical.

7. A method according to any one of the preceding claims, characterized in that the monomer of formula (II) is selected from: * vinyl ester type monomers represented by the following formula (11-1): * α-olefin type monomers represented by the following formula (II-2): in which R 11 represents a hydrogen atom or an alkyl radical, and R 12 represents an alkyl radical or a possibly substituted aryl radical, * N-vinyl type monomers represented by the following formula (111-1): * acrylate and alkacrylate type monomers represented by the following formula (II-3): in which R 11 represents a hydrogen atom or an alkyl radical and R 16 represents an alkyl radical.

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

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

10. A 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 formula (II) varies from 30 to 60% by mass relative to the total mass of the reaction medium.

11. A 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.

12. Copolymer, preferably degradable, said copolymer being characterized in that it comprises at least thioester bonds, and that it results from radical ring-opening polymerization: (i) of at least one cyclic monomer selected from the thionolactides of the following formula (I): in which: - X is an oxygen atom or a sulfur atom; - R 1 , R 2 , R 3 , and R 4Independently of each other, they represent a hydrogen atom, a halogen atom, a group chosen from an alkyl radical, a haloalkyl radical, a possibly substituted phenyl radical, a cyano group, a possibly substituted alkyl-phenyl radical, a possibly substituted haloalkyl-phenyl radical, a carboxylic acid radical, and a CO2R ester radical. 5 with R 5 representing an alkyl radical, a phosphonic acid radical, a phosphonic acid ester radical P(O)(OR 6a )(GOLD 6b ) with R 6a representing a hydrogen atom or an alkyl radical, and R 6b representing an alkyl radical, a sulfonic acid radical, a sulfonic acid ester radical SO3R 7 with R 7 representing an alkyl radical or a haloalkyl radical, and an amide radical C(O)NR 8a R 8b , with R 8a and R 8bindependently of each other, representing a hydrogen atom or an alkyl radical, or together forming an alkyl radical; and (ii) of at least one monomer comprising an ethylenic unsaturation selected from the following monomers of formula (II): in which: - R 9 represents a hydrogen atom, or a fluorine atom; - R 10 represents a hydrogen atom, or a fluorine atom; - R 11 represents a hydrogen atom, an alkyl radical, a fluorine atom, or a chlorine atom; - R 12 represents a hydrogen atom, or a group chosen from the following groups: * an alkyl radical, * a haloalkyl radical, * an aryl radical, possibly substituted, * a possibly substituted alkyl-aryl radical, * an imidazolyl group, * an alkylimidazolium group, * a carbazoyl group, * a group of the following formula (III): \ O N_ / / R« R 14 (III) in which the asterisk (*) represents the point of attachment of the group of formula (III) to the carbon atom of the compound of formula (II), and R 13 and R 14 , identical or different, represent a hydrogen atom, an alkyl radical, a possibly substituted alkyl-aryl radical, a possibly substituted aryl radical, a glycidyl group, or R 13 and R 14 together with the nitrogen and carbon atoms of the formula group (III) to which they are linked, form a heterocarbon ring comprising 4 to 7 carbon atoms (including the carbon atom bearing the oxygen atom), * a group -OC(O)R 15 , with R 15 representing an alkyl radical, a haloalkyl radical, a possibly substituted alkyl-aryl radical, a possibly substituted aryl radical, * a group -C(O)OR 16 , with R 16 representing an alkyl radical, a haloalkyl radical, a possibly substituted alkyl-aryl radical, a possibly substituted aryl radical, * a phosphonic acid group, * an ester group of phosphonic acid P(O)(OR 17a )(GOLD 17b ), with R 17a representing a hydrogen atom or an alkyl radical, and R 17b representing an alkyl radical, * a sulfonic acid group, * an ester group of sulfonic acid SO3R 18 , with R 18 representing an alkyl radical or a haloalkyl radical, and * an amide group C(O)NR 19a R 19b , with R 19a and R 19b , 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 ratio 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 a precursor monomer in a radical polymerization.

16. Thionolactide for the implementation of a process as defined in any one of claims 1 to 11, corresponding to the following formula (I'): in which: - X, R 1 , R 2 , R 3 , and R4 are as defined in any one of claims 1 to 5, - excluding thionolactides (1-1) and (I-2) as defined in claim 5.

17. Thionolactide according to claim 16 selected from the thionolactides of formulas (I-3) to (1-13) as defined in claim 5.

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