Radical Polymerization Method of Thionolactide

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 polymerization, in particular using at least one thionolactide monomer. The present invention also relates to copolymers, preferably degradable copolymers, obtained by carrying out this method, the use of said thionolactide monomers as precursor monomers in radical polymerization, and to specific thionolactides.

Description

[Technical field]

[0001] The present invention relates to a method for preparing copolymers, preferably degradable or biodegradable copolymers, from thionolactide. More particularly, the present invention relates to a method for preparing copolymers, preferably degradable copolymers, by radical ring-opening polymerization, in particular carrying out at least one thionolactide type monomer, to the copolymers, preferably degradable copolymers, obtainable by carrying out this method, to the use of said thionolactide type monomers as precursor monomers in radical polymerization, as well as to certain thionolactides. [Background technology]

[0002] Currently, most synthetic polymers are synthesized by radical polymerization of vinyl monomers such as ethylene, methyl methacrylate, styrene and vinyl acetate. Radical synthesis methods have the advantage of allowing a wide range of functionality and therefore the synthesis of many materials. The application of controlled radical polymerization techniques, developed towards the end of the 20th century, also allows the control of the average molar mass and molar mass distribution of the polymer, allowing the synthesis of polymers and copolymers with complex architectures, such as block copolymers, gradient copolymers or star copolymers.

[0003] One of the main drawbacks of polymers produced by radical polymerization is that they are difficult to degrade. In fact, the different monomer units are linked to each other by carbon-carbon (C-C) bonds, which are highly resistant to degradation. This can lead to environmental damage and also limit the application of these polymers in the medical field, so it is important to avoid the accumulation of high molecular weight polymers in the body.

[0004] One way to introduce degradable properties into synthetic polymers obtained by radical polymerization is to use cyclic comonomers polymerized by radical ring-opening polymerization (RROP). These monomers are mainly of two types: vinyl and exo-methylene. If the vinyl or exo-methylene type cyclic comonomer has a degradable functional group, it can be incorporated into the polymer backbone, making it degradable.

[0005] Polymerization of these monomers proceeds by radical addition across the double bond followed by ring-opening and formation of linear species according to the following reaction schemes (1) and (2) for vinyl and exo-methylene monomers, respectively. [ka] [ka]

[0006] Vinyl type monomers include vinylcyclopropanes, introduced in the 1960s. Exo-methylene monomers include ketene acetals, introduced in the 1980s, including 2-methylene-1,3-dioxane (MDO), which are converted to esters during free radical polymerization [Y=Y'=O in reaction scheme (2)]. The monomer MDO has been studied in controlled radical polymerizations, notably in Hedir et al, Biomacromolecules, 2015, 16, 2049-2058. In general, ketene acetals copolymerize easily with vinyl esters and vinyl ethers, but more difficultly with styrene 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 aryl sulfides (e.g., 2-methyl-7-methylene-1,5-dithiacyclooctane), have also been described.

[0007] More recently, the use of the thionolactone dibenzo[c,e]oxepane-5-thione (DOT) in radical polymerization was described. Copolymers of this monomer with acrylonitrile, N,N-dimethylacrylamide, poly(ethylene glycol) methyl ether acrylate (PEGA), methyl acrylate, and maleimide were prepared. However, DOT is inactive in the presence of methyl methacrylate, retards the radical polymerization of styrene without being incorporated into the polymer backbone, and inhibits the polymerization of vinyl acetate and N-vinylpyrrolidone. Furthermore, its synthesis is complex. Other thionolactones, such as γ-phenyl-γ-butyrolactone and 4-thionophthalide, were tested in copolymerization with different monomers and found to be inactive [Bingham et al, Chem. Commun., 2019, 55, 55]. Finally, Ivanchenko et al [Polymer Chemistry, 2021, 12, 1931-1938] described the use of thionocaprolactone, which was found to be inert towards n-butyl acrylate.

[0008] As a result, there is a need for synthetic methods that provide easy access, preferably in good yields, to new synthetic polymers with various structures, preferably degradable or even biodegradable. There is also a need for precursor monomers that can react with comonomers with various structures, for example activated comonomers such as styrene or acrylates, as well as non-activated comonomers such as vinyl esters. Surprisingly, the inventors have developed a radical ring-opening polymerization method which makes it possible to achieve these aims, which method offers a particularly wide range of reactivity.

[0009] Thus, a first object of the present invention is a method for preparing at least one copolymer, preferably at least one degradable copolymer, comprising at least one step of radical polymerization by ring-opening of at least one cyclic monomer and at least one monomer containing ethylenic unsaturation, in the presence of a radical polymerization initiator, said method comprising: (i) the cyclic monomer is represented by the following formula (I): [ka] During the ceremony, -X is an oxygen atom or a sulfur atom, -R 1 , R 2 , R 3 and R 4 are each independently a hydrogen atom, a halogen atom, an alkyl group, a haloalkyl group, an optionally substituted phenyl group, a cyano group (CN), an optionally substituted alkyl-phenyl group, an optionally substituted haloalkyl-phenyl group, a carboxylic acid group (COOH), R 5 CO represents an alkyl group 2 R 5 , phosphonic acid group (PO(OH) 2 ), R 6a represents a hydrogen atom or an alkyl group, R 6b Phosphonate group P(O)(OR) represents an alkyl group 6a )(OR 6b ), R 7 represents an alkyl or haloalkyl group; 3 R 7 , sulfonic acid group (SO 3 H), R 8a and R 8b represents a hydrogen atom or an alkyl group, or an amide group C(O)NR 8a R 8b represents a group selected from the group consisting of is selected from thionolactides of formula (I): (ii) the monomer containing ethylenic unsaturation is represented by formula (II): [ka] During the ceremony, -R 9 represents a hydrogen atom or a fluorine atom, -R 10 represents a hydrogen atom or a fluorine atom, -R 11represents a hydrogen atom, an alkyl group, a fluorine atom or a chlorine atom, -R 12 is a hydrogen atom or one of the following groups: *Alkyl group *Haloalkyl group *Optionally substituted aryl groups, *Optionally substituted alkyl-aryl groups, *Imidazolyl group *Alkyl imidazolium group, *Carbazolyl group, * a group of formula (III) [ka]

[0010] where the asterisk (*) represents the anchor point of the group of formula (III) to a carbon atom of the compound of formula (II), and R 13 and R 14 are the same or different and each represents a hydrogen atom, an alkyl group, an optionally substituted alkylaryl group, an optionally substituted aryl group, or a glycidyl group, or R 13 and R 14 together with the nitrogen atom and the carbon atom of the group of formula (III) to which they are attached form a heterocarbocycle containing 4 to 7 carbon atoms (including the carbon atom bearing an oxygen atom); Group of formula (III) *-OC(O)R 15 A group, wherein R 15 represents an alkyl group, a haloalkyl group, an optionally substituted alkyl-aryl group, or an optionally substituted aryl group; -OC(O)R 15 basis *-C(O)OR 16 A group, wherein R 16 represents an alkyl group, a haloalkyl group, an optionally substituted alkylaryl group, or an optionally substituted aryl group; -C(O)OR 16 basis *Phosphonic acid group (PO(OH) 2 ), *Phosphonate ester group P(O)(OR 17a )(OR 17b ) in which R 17a represents a hydrogen atom or an alkyl group, R 17b represents an alkyl group, and a phosphonate group P(O)(OR 17a )(OR 17b ) *Sulfonic acid group (SO 3 H), *Sulfonic acid ester group SO 3 R 18 wherein R 18 represents an alkyl group or a haloalkyl group, and a sulfonate group SO 3 R 18 , and *Amide group C(O)NR 19a R 19b wherein R 19a and R 19b represent, independently of one another, a hydrogen atom or an alkyl group or together form an alkyl group, an amide group C(O)NR 19a R 19b represents a group selected from selected from monomers of formula (II) By this method it is now possible to obtain in a simple manner, preferably in good yield, copolymers, preferably degradable copolymers, whose degradability can be easily adjusted by varying the respective proportions of the monomers of formula (I) and (II).

[0011] During the process of the present invention, the ring-opening of the cyclic monomer (I) allows the formation of units containing thioester and ester bonds in the copolymer when X is an oxygen atom. Furthermore, some of the cyclic monomer (I) can also react with the monomer (II) by radical polymerization without ring-opening. The copolymer thus obtained further comprises cyclic monomer units (I) containing ortho-dithioester and / or thioacetal bonds in contrast to the monomer units (I) containing thioester bonds and ester bonds when X is an oxygen atom.

[0012] Thus, the degradability of the copolymer is provided by the presence of thioester bonds, and optionally orthodithioester and / or thioacetal bonds, as a result of the incorporation of the monomer of formula (I) into the copolymer backbone. The greater their proportion relative to the monomer of formula (II), the greater the degradability of the copolymer. Thus, after degradation, the length of the fragments obtained is inversely proportional to the amount of monomer of formula (I) incorporated into the polymer backbone. Furthermore, the chemical groups at the ends of the fragments obtained are functional and reactive. Furthermore, the thionolactide monomer of formula (I) carried out in the free radical copolymerization reaction according to the method according to the invention can be easily synthesized according to conventional techniques known to those skilled in the art from non-sulfur precursors such as commercially available α-hydroxy acids to form lactides which, by thionation, give thiolactides. Moreover, monomer (I) has the ability to react with both activated monomers, such as styrene, its derivatives or acrylates, and non-activated monomers, such as vinyl esters. Finally, most monomers of formula (II) are commercially available.

[0013] The monomer (I) of the present invention is different from monomers known in the prior art, such as thionolactide (or dithionolactide), which contains -S(C=O)- units. Thus, dithionolactide does not contain a C=S thiocarbonyl bond. This cyclic di(thioester) can be polymerized by non-radical ring opening using a base catalyst to produce degradable poly(thioester). This monomer cannot be copolymerized with the comonomer (II) of the present invention by a radical pathway.

[0014] According to the invention, a degradable polymer means a polymer whose backbone contains bonds that can be easily cleaved, in particular by chemical hydrolysis, aminolysis or enzymatic digestion, to give smaller, possibly less polluting molecules, said bonds being in particular thioester bonds, optionally orthodithioester and / or thioacetal bonds.

[0015] According to the present invention, the term "thionolactide monomer of formula (I)" refers to a thionolactide monomer of formula (I), 1 , R 3 =H and R 2 , R 4 =CH 3 ) as well as thionolactide itself, which corresponds to the compound of formula (I) (wherein R 1 , R 2 , R 3 , R 4 is as defined in the present invention). Thionolactide Monomer (I) X is an oxygen atom or a sulfur atom, and is preferably an oxygen atom.

[0016] R 1 , R 2 , R 3 and R 4 are each independently a hydrogen atom, a halogen atom, an alkyl group, a haloalkyl group, an optionally substituted phenyl group, a cyano group (CN), an optionally substituted alkyl-phenyl group, an optionally substituted haloalkyl-phenyl group, a carboxylic acid group (COOH), R 5 CO represents an alkyl group 2 R 5 , phosphonic acid group (PO(OH) 2 ), R 6a represents a hydrogen atom or an alkyl group, R 6b represents an alkyl group, and the phosphonate group P(O)(OR 6a R 6b ) 2 , sulfonic acid group (SO 3 H), R 7 represents an alkyl or haloalkyl group; 3 R 7 , R 8a and R 8b each independently represents a hydrogen atom or an alkyl group, or together form an alkyl group, an amide group C(O)NR 8a R 8b represents a group selected from R 1 , R2 , R 3 and / or R 4 The halogen atom as a group is preferably a fluorine atom.

[0017] R 1 , R 2 , R 3 and / or R 4 The alkyl group as a radical may be linear or branched, cyclic or acyclic. The alkyl group is preferably linear and acyclic. The alkyl group may contain 1 to 22 carbon atoms, preferably 1 to 6 carbon atoms, particularly preferably 1 to 3 carbon atoms. The alkyl group is advantageously a methyl or ethyl group. In the present invention, the term "haloalkyl" refers to an alkyl group containing one or more halogen atoms, preferably selected from chlorine and fluorine atoms.

[0018] base R 1 , R 2 , R 3 and / or R 4 The haloalkyl group as may be linear or branched, cyclic or acyclic. The haloalkyl group is preferably linear and acyclic. The haloalkyl group may contain 1 to 18 carbon atoms, preferably 1 to 6 carbon atoms, particularly preferably 1 to 3 carbon atoms. The haloalkyl group is advantageously a trifluoromethyl, fluoromethyl, chloromethyl or chloroethyl group.

[0019] In the present invention, the term "optionally substituted phenyl" refers to the group R 1 , R 2 , R 3 and / or R 4 This means that the phenyl group as may be substituted with one or more substituents such as halogen atoms, preferably selected from chlorine and fluorine atoms, alkyl atoms and haloalkyl atoms.

[0020] The haloalkyl group as a substituent of the phenyl group preferably contains from 1 to 3 carbon atoms. Advantageously, it is a trifluoromethyl group. The alkyl group as a substituent of the phenyl group preferably contains 1 to 3 carbon atoms. It is advantageously a methyl group. The phenyl group substituted with one or more halogen atoms is preferably a pentafluorophenyl group -C 6 F 5 It is.

[0021] R 1 , R 2 , R 3 and / or R 4 An optionally substituted alkyl-phenyl group as a group is a radical that contains at least one alkyl group and at least one optionally substituted phenyl group that are directly linked via a covalent carbon-carbon bond (of the optionally substituted phenyl group), the optionally substituted phenyl and alkyl groups being represented by R 1 , R 2 , R 3 and R 4 The alkyl group is as defined above. The alkyl group is directly bonded to the thionolactide via a carbon atom. The optionally substituted alkyl-phenyl group is preferably a benzyl or pentafluorobenzyl group.

[0022] R 1 , R 2 , R 3 and / or R 4 An optionally substituted haloalkyl-phenyl group as a group is a radical that contains at least one haloalkyl group and at least one optionally substituted phenyl group linked directly by a carbon (of the optionally substituted phenyl group)-carbon (of the haloalkyl group) covalent bond, the optionally substituted phenyl and haloalkyl groups being represented by R 1 , R 2 , R 3 and R 4 The groups are as defined above. The haloalkyl group is attached directly to the thionolactide via a carbon atom.

[0023] R 5The alkyl group as a radical may be linear or branched, cyclic or acyclic. The alkyl group is preferably linear and acyclic. The alkyl group may contain 1 to 22 carbon atoms, preferably 1 to 6 carbon atoms, particularly preferably 1 to 3 carbon atoms. The alkyl group is advantageously a methyl or ethyl group.

[0024] R 6a or R 6b The alkyl group as a radical may be linear or branched, cyclic or acyclic. The alkyl group is preferably linear and acyclic. The alkyl group may contain 1 to 22 carbon atoms, preferably 1 to 6 carbon atoms, particularly preferably 1 to 3 carbon atoms. The alkyl group is advantageously a methyl or ethyl group.

[0025] R 7 The alkyl group as a radical may be linear or branched, cyclic or acyclic. The alkyl group is preferably linear and acyclic. The alkyl group may contain 1 to 22 carbon atoms, preferably 1 to 6 carbon atoms, particularly preferably 1 to 3 carbon atoms. The alkyl group is advantageously a methyl or ethyl group.

[0026] R 7 The haloalkyl group as a group may be linear or branched, cyclic or acyclic. The haloalkyl group is preferably linear and acyclic. The haloalkyl group may contain 1 to 18 carbon atoms, preferably 1 to 6 carbon atoms, particularly preferably 1 to 3 carbon atoms. The haloalkyl group is advantageously a trifluoromethyl group.

[0027] R a Group or R 8b The alkyl group as a radical may be linear or branched, cyclic or acyclic. The alkyl group is preferably linear and acyclic. The alkyl group may contain 1 to 22 carbon atoms, preferably 1 to 6 carbon atoms, particularly preferably 1 to 3 carbon atoms. The alkyl group is advantageously a methyl or ethyl group.

[0028] R 8a and R 8bWhen the groups taken together form an alkyl group, R 8a and R 8b together give a nitrogen ring which in particular forms an alkyl group containing 5 carbon atoms (a piperidine ring).

[0029] R of thionolactide(I) 1 , R 2 , R 3 and R 4 Modulation of the groups makes it possible to increase its reactivity towards non-activated monomers (II), such as, for example, monomers of the vinyl ester type, or towards activated monomers (II), such as, for example, monomers of the acrylate, acrylamide or styrene type.

[0030] R 1 , R 2 , R 3 and R 4 are each independently preferably selected from a hydrogen atom, a halogen atom, an alkyl group, a haloalkyl group, an optionally substituted phenyl group, an optionally substituted alkyl-phenyl group and an optionally substituted haloalkyl-phenyl group, particularly preferably a hydrogen atom, a halogen atom, an alkyl group, a haloalkyl group and an optionally substituted phenyl group.

[0031] According to a preferred embodiment of the present invention, the following is true. *R 1 =H or CH 3 , *R 2 =H, CH 3 , C 6 H 5 , C.F. 3 , C 6 F 5 , C 6 H 4 -CF 3 , F, C.H. 2 F, C.H. 2 Cl or C 2 H 4 -Cl, *R 3 =H or CH 3 , *R4 =H, CH 3 , C 6 H 5 , C.F. 3 , C 6 F 5 , C 6 H 4 -CF 3 , F, C.H. 2 F, C.H. 2 Cl or C 2 H 4 -Cl

[0032] The thionolactide of formula (I) is advantageously chosen from the following thionolactides: (i)R 2 and R 4 is as defined in the present invention except for a hydrogen atom, and is particularly preferably an alkyl group; (ii)R 3 and R 4 is as defined herein except for hydrogen atoms, and is particularly preferably an alkyl group; and (iii)R 1 , R 2 , R 3 or R 4 Thionolactide, where R is a hydrogen atom. In thionolactide (i), R 1 and R 3 is preferably a hydrogen atom. In the thionolactide (ii), R 1 and R 2 is preferably a hydrogen atom. The thionolactides (i) and (ii) promote copolymerization with the activated monomer (II). The thionolactide (iii) promotes copolymerization with the unactivated monomer (II).

[0033] According to a particular embodiment of the present invention, all R 1 and R 2 The group is any R 3 and R 4 This results in the "symmetric" thionolactide (I), which is easier to prepare. The thionolactide of formula (I) is advantageously selected from the thionolactides of formulae (I-1) to (I-13) shown in Table 1 below.

[0034] [Table 1]

[0035] Among these thionolactides of the formulas (I-1) to (I-14), the thionolactides of the formulas (I-1), (I-13) and (I-14) are particularly preferred. Monomer (II) R 9 preferably represents a hydrogen atom. R 10 preferably represents a hydrogen atom. R 11 preferably represents a hydrogen atom or an alkyl group.

[0036] base R 11 The alkyl group as may be linear or branched, cyclic or acyclic. The alkyl group is preferably linear and acyclic. The alkyl group may contain 1 to 5 carbon atoms, preferably 1 to 3 carbon atoms. The alkyl group is advantageously a methyl group.

[0037] base R 12 The alkyl group as may be linear or branched, cyclic or acyclic. The alkyl group is preferably linear and acyclic. The alkyl group may contain 1 to 22 carbon atoms, preferably 1 to 10 carbon atoms, particularly preferably 1 to 5 carbon atoms, and the alkyl group is optionally substituted with a hydroxyl radical.

[0038] R 12As examples of alkyl groups as groups, the following radicals may be mentioned: 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, preferably the methyl or hexyl radical.

[0039] base R 12 The haloalkyl group as may be linear or branched, cyclic or acyclic. The haloalkyl group is preferably linear and acyclic. The haloalkyl group may contain 1 to 22 carbon atoms, preferably 1 to 5 carbon atoms.

[0040] R 12 An aryl group as a radical can be a monocyclic or polycyclic aromatic hydrocarbon group optionally substituted with an alkyl group containing 1 to 5 carbon atoms, or an alkoxyl group containing 1 to 5 carbon atoms.

[0041] R 12 As examples of aryl groups there may be mentioned in particular phenyl, trityl, naphthalenyl, anthracenyl and pyrenyl groups, among which the phenyl group is particularly preferred.

[0042] base R 12 An optionally substituted alkyl-aryl group as defined above is a radical comprising at least one alkyl group and at least one optionally substituted aryl group which are directly linked via a covalent carbon-carbon bond (of the optionally substituted aryl group), the optionally substituted aryl and alkyl groups being preferably linked together by a group R 12 The alkyl group is bonded directly to the ethylenic function (double bond) of the monomer (II) via a carbon atom. The optionally substituted alkyl-aryl group is advantageously a benzyl, p-methoxybenzyl or pentafluorobenzyl group.

[0043] base R 12 The alkyl substituent of the alkylimidazolium group as R preferably contains 1 to 16 carbon atoms, particularly preferably 1 to 5 carbon atoms. 12 The alkylimidazolium group as a group is preferably Br - , B.F. 4 - and P.F. 6 - The compound includes a counter ion selected from:

[0044] Group of formula (III) R 13 and / or R 14 The alkyl group as a group may be linear or branched, cyclic or acyclic. The alkyl group is preferably linear. The alkyl group may contain 1 to 22 carbon atoms, preferably 1 to 5 carbon atoms.

[0045] base R 13 and / or R 14 As examples of alkyl groups as the radicals, the following may be mentioned: methyl, ethyl, iso-propyl, n-butyl, 2-butyl, iso-butyl, tert-butyl, n-pentyl, iso-pentyl, neo-pentyl, tert-pentyl, 2-methylbutyl, hexyl, noctyl, iso-octyl, 2-ethyl-1-hexyl, 2,2,4-trimethylpentyl, nonyl, neo-decanyl, decyl, dodecyl, octadecyl, behenyl, cyclohexylmethyl, adamantyl and cyclohexyl.

[0046] R 13 and / or R 14 An aryl group as a radical can be a monocyclic or polycyclic aromatic hydrocarbon group optionally substituted with an alkyl group containing 1 to 5 carbon atoms, or an alkoxyl group containing 1 to 5 carbon atoms.

[0047] R 13 and / or R 14As examples of aryl groups there may be mentioned in particular phenyl, trityl, naphthalenyl, anthracenyl and pyrenyl groups, among which the phenyl group is particularly preferred.

[0048] R 13 and / or R 14 An optionally substituted alkyl-aryl group as a group is a radical that contains at least one alkyl group and at least one optionally substituted aryl group that are directly linked via a covalent carbon-carbon bond (of the optionally substituted aryl group), and the optionally substituted aryl and alkyl groups are represented by R 13 and R 14 The alkyl group is as defined above. 13 The nitrogen atom of formula (III) and R 14 The optionally substituted alkyl-aryl group is preferably a benzyl or pentafluorobenzyl group.

[0049] R 13 and R 14 together with the nitrogen and carbon atoms of the group of formula (III) to which they are attached form a heterocarbocyclic ring, this may in particular be a pyrrolidone, piperidone or caprolactam ring.

[0050] According to a preferred embodiment of the present invention, identical or different R 13 and R 14 represents a hydrogen atom or an alkyl group, or R 13 and R 14 together with the nitrogen and carbon atom of the group of formula (III) to which they are attached form a heterocarbocycle containing from 4 to 7 carbon atoms (including the carbon atom bearing the oxygen atom).

[0051] According to a particularly preferred embodiment, R 13 and R 14are identical and represent a methyl radical or, together with the nitrogen and carbon atom of the group of formula (III) to which they are attached, form a pyrrolidone or caprolactam ring.

[0052] -OC(O)R 15 basis R 15 The alkyl group as a group may be linear or branched, cyclic or acyclic. The alkyl group is preferably linear and acyclic. The alkyl group may contain 1 to 22 carbon atoms, preferably 1 to 5 carbon atoms.

[0053] R 15 Examples of alkyl groups as groups may include the following 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, isooctyl, 2-ethyl-1-hexyl, 2,2,4-trimethylpentyl, nonyl, neo-decanyl, decyl, dodecyl, octadecyl, behenyl, cyclohexylmethyl, adamantyl and cyclohexyl.

[0054] R 15 An aryl group as a radical can be a monocyclic or polycyclic aromatic hydrocarbon group optionally substituted with an alkyl group containing 1 to 5 carbon atoms, or an alkoxyl group containing 1 to 5 carbon atoms.

[0055] R 15 As examples of aryl groups there may be mentioned in particular phenyl, trityl, naphthalenyl, anthracenyl and pyrenyl groups, among which the phenyl group is particularly preferred.

[0056] base R 15An optionally substituted alkyl-aryl group as defined above is a radical comprising at least one alkyl group and at least one optionally substituted aryl group directly linked via a covalent carbon-carbon bond (of the optionally substituted aryl group), wherein the optionally substituted aryl and alkyl groups are 15 The radicals are as defined above. The alkyl radical is directly bonded to the carbon atom of the ester functional group via a carbon atom. The optionally substituted alkyl-aryl radical is advantageously a benzyl or pentafluorobenzyl radical.

[0057] R 15 Haloalkyl groups as groups can be linear or branched, cyclic or acyclic. Haloalkyl groups are preferably linear and acyclic. Haloalkyl groups can contain 1 to 22 carbon atoms, preferably 1 to 5 carbon atoms.

[0058] R 15 preferably represents an alkyl or haloalkyl group, and particularly preferably represents an alkyl group such as a methyl or t-butyl group. -C(O)OR 16 basis R 16 The alkyl group as a group may be linear or branched, cyclic or acyclic. The alkyl group is preferably linear and acyclic. The alkyl group may contain 1 to 22 carbon atoms, preferably 1 to 5 carbon atoms.

[0059] R 16 Examples of alkyl groups as groups may include the following groups: 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, isooctyl, 2-ethyl-1-hexyl, 2,2,4-trimethylpentyl, nonyl, neo-decanyl, decyl, dodecyl, octadecyl, behenyl, isobornyl, cyclohexylmethyl, adamantyl and cyclohexyl.

[0060] R16 An aryl group as a radical can be a monocyclic or polycyclic aromatic hydrocarbon group optionally substituted with an alkyl group containing 1 to 5 carbon atoms, or an alkoxyl group containing 1 to 5 carbon atoms.

[0061] R 16 As examples of aryl groups there may be mentioned in particular phenyl, trityl, naphthalenyl, anthracenyl and pyrenyl groups, of which the phenyl group is particularly preferred.

[0062] base R 16 An optionally substituted alkyl-aryl group as defined above is a radical comprising at least one alkyl group and at least one optionally substituted aryl group which are directly linked via a covalent carbon-carbon bond (of the optionally substituted aryl group), the optionally substituted aryl and alkyl groups being preferably linked together by a group R 16 The alkyl group is bonded directly to the carbon atom of the ester functional group via a carbon atom. The optionally substituted alkyl-aryl group is advantageously a benzyl or pentafluorobenzyl group.

[0063] R 16 Haloalkyl groups as groups can be linear or branched, cyclic or acyclic. Haloalkyl groups are preferably linear and acyclic. Haloalkyl groups can contain 1 to 22 carbon atoms, preferably 1 to 5 carbon atoms.

[0064] R 16 preferably represents an alkyl group, in particular a methyl or t-butyl group. R 17a Group or R 17b The alkyl group as a radical may be linear or branched, cyclic or acyclic. The alkyl group is preferably linear and acyclic. The alkyl group may contain 1 to 22 carbon atoms, preferably 1 to 6 carbon atoms, particularly preferably 1 to 3 carbon atoms. The alkyl group is advantageously a methyl or ethyl group.

[0065] R18 The alkyl group as a radical may be linear or branched, cyclic or acyclic. The alkyl group is preferably linear and acyclic. The alkyl group may contain 1 to 22 carbon atoms, preferably 1 to 6 carbon atoms, particularly preferably 1 to 3 carbon atoms. The alkyl group is advantageously a methyl or ethyl group.

[0066] R 18 The haloalkyl group as a group may be linear or branched, cyclic or acyclic. The haloalkyl group is preferably linear and acyclic. The haloalkyl group may contain 1 to 18 carbon atoms, preferably 1 to 6 carbon atoms, particularly preferably 1 to 3 carbon atoms. The haloalkyl group is advantageously a trifluoromethyl group.

[0067] R 19a or R 19b The alkyl group as a radical may be linear or branched, cyclic or acyclic. The alkyl group is preferably linear and acyclic. The alkyl group may contain 1 to 22 carbon atoms, preferably 1 to 6 carbon atoms, particularly preferably 1 to 3 carbon atoms. The alkyl group is advantageously a methyl or ethyl group.

[0068] R 19a and R 19b When the groups taken together form an alkyl group, R 19a and R 19b together give a nitrogen ring which in particular forms an alkyl group containing 5 carbon atoms (a piperidine ring).

[0069] According to a particular embodiment, the monomer of formula (II) is *Vinyl ester monomer represented by the following formula (II-1): [ka] (In the formula, R 15 is as defined in the present invention).

[0070] *α-olefin monomer represented by the following formula (II-2) [ka] (In the formula, R 11 represents a hydrogen atom or an alkyl group as defined in the present invention, R 12 represents an alkyl group or an optionally substituted aryl group as defined herein.

[0071] *N-vinyl monomer represented by the following formula (III-1) [ka] (In the formula, R 13 and R 14 is as defined in the present invention).

[0072] *Acrylate and alkacrylate monomers represented by the following formula (II-3) [ka] (In the formula, R 11 represents a hydrogen atom or an alkyl group as defined in the present invention, R 16 represents an alkyl group as defined in the present invention) is selected from.

[0073] Among the monomers of formula (II-1), vinyl acetate, vinyl pivalate, vinyl trifluoroacetate, vinyl chloroacetate, vinyl propionate, vinyl butyrate, vinyl neodecanoate (R 15 =C 9 H 19 , mixtures of isomers) and vinyl trifluorobutyrate. Among these monomers of formula (II-1), vinyl acetate and vinyl pivalate are particularly preferred. Monomers of formula (II-2) include ethylene and octene, with ethylene being particularly preferred.

[0074] Among the monomers of formula (III-1), acyclic N-vinyl monomers such as N-vinylformamide, N-vinylacetamide, and N-methyl-N-vinylacetamide, and cyclic N-vinyl monomers (R 13 and R 14 (wherein, together with the nitrogen atom and the carbon atom of the group of formula (III-1) to which they are attached, they form a heterocarbocycle) can be mentioned in particular. Among such monomers of formula (III-1), N-vinylacetamide and N-vinylpyrrolidone are particularly preferred.

[0075] Among the monomers of formula (II-3), mention may especially be made of methyl acrylate, n-butyl acrylate, tert-butyl acrylate, 2-ethylhexyl acrylate, methyl methacrylate, tert-butyl methacrylate, isobornyl methacrylate or adamantyl methacrylate.

[0076] According to the method according to the invention, the proportion of the monomers of formula (I) is preferably selected such that the monomer or monomers of formula (I) represent up to 50% by number relative to the total number of monomers of formulas (I) and (II). According to a particularly preferred embodiment, the monomer or monomers of formula (I) represent about 5-30% by number, even more preferably about 10-20% by number, relative to the total number of monomers of formulas (I) and (II). Indeed, if the proportion of monomers of formula (I) is less than 5% by number, the decomposition rate of the polymer is not high and is of little importance compared to non-degradable polymers. If the proportion of monomers of formula (I) exceeds 30% by number, the radical polymerization process by ring opening is impaired and in particular slowed down.

[0077] For purposes of this invention, a radical polymerization initiator refers to a chemical species capable of forming a free radical, ie, a radical having one or more unpaired electrons in its outer shell.

[0078] According to the process according to the invention, the radical polymerization initiator is preferably selected from organic peroxides and hydroperoxides, azo derivatives and radical-generating redox couples (redox systems).

[0079] Among 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 peroxypivalate, t-butyl peroxypivalate, diisopropyl 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.

[0080] Among the azo derivatives, 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'-dimethyleneisobutylamidine) dihydrochloride, 2,2'-azobis-(2-amidinopropane) dihydrochloride, 2,2'-azobis-(N,N'-dimethyleneisobutylamidine ... Particular mention may be made of 2,2'-azobis-(N,N'-dimethylisobutylamine), 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-hydroxyethylpropionamide), 2,2'-azobis-(isobutylamide) dihydrate, 2,2'-azobis-(2,2,4-trimethylpentane) and 2,2'-azobis-(2-methylpropane). Among these azo derivatives, 2,2'-azobis(isobutyronitrile) and 1,1'-azobis-(cyclohexanecarbonitrile) are particularly preferred.

[0081] The redox system is, for example, selected from systems including the following combinations: - mixtures of hydrogen peroxide, dialkyl peroxides, hydroperoxides, peresters, percarbonates and similar compounds with iron salts, titanium salts, zinc formaldehyde sulfoxylate or sodium formaldehyde sulfoxylate and reducing sugars; - mixtures of alkali metal or ammonium persulfates, perborates or perchlorates with alkali metal bisulfites, such as sodium metabisulfite, and reducing sugars; Mixtures of alkali metal persulfates with arylphosphinic acids, such as benzenephosphonic acid, and reducing sugars.

[0082] Among such redox systems, the associations of ammonium persulfate and sodium formaldehyde sulfoxylate, and tert-butyl hydroperoxide and ascorbic acid are particularly preferred.

[0083] It is also possible to use photochemical initiators in ultraviolet (UV) or visible light. Examples of UV initiators include 2,2-dimethoxy-2-phenylacetophenone, benzophenone / amine or benzophenone / alcohol pairs. Thioxanthone can be used as a visible initiator. Finally, some xanthate or trithiocarbonate type RAFT control agents can also be used, which are also good photochemical initiators in the UV and visible range.

[0084] The amount of radical polymerization initiator used according to the method according to the invention is generally determined so that the amount of radicals generated is not more than about 5 mol %, preferably at most about 1 mol %, relative to the total amount of monomers of formulae (I) and (II).

[0085] The process of radical polymerization by ring opening of the monomers of formulae (I) and (II) can be carried out in bulk (without solvent) or in solution in a solvent, particularly selected so that the reaction medium remains homogeneous throughout the polymerization reaction. Generally, the solvent is organic, but it is not impossible to use aqueous solvents such as water or mixtures of water and cosolvents, if justified by the solubility of the monomers. 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 precipitation or in a dispersion, emulsion or suspension. According to a preferred embodiment of the invention, water, a water-alcohol mixture or an organic solvent is used as the reaction medium, with organic solvents being preferred.

[0086] The total amount of polymerizable material in the reaction medium (total amount of monomers of formula (I) and formula (II)) can be 100% if the polymerization is carried out in bulk, i.e. without a solvent. If the polymerization is carried out in a solvent, this total amount can range from about 10% to 90% by weight, preferably from about 20% to 80% by weight, and even more preferably from about 30% to 60% by weight, based on the total weight of the reaction medium.

[0087] The polymerization step of the process according to the invention can be carried out at a temperature ranging from about 5 to 150° C., depending on the nature of the monomers of formulae (I) and (II) used in the reaction. According to a preferred embodiment of the process according to the invention, the polymerization step is carried out at a temperature ranging from about 20 to 130° C., even more preferably from about 40 to 110° C. The duration of the polymerization step generally ranges from about 1 to 12 hours, even more preferably from about 2 to 8 hours.

[0088] As mentioned 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 an alternative of the method according to the invention, it is nevertheless possible to carry out the polymerization step in the presence of a polymerization control agent, thus providing access to copolymers, preferably degradable copolymers, block, composition gradient, comb, star graft or even hyperbranched copolymers. In fact, various controlled radical polymerization methods are known, making it possible to obtain polymers with controlled structure and mass. These methods are defined according to the chemical nature of the control agent involved. The present invention may include control agents for controlled radical polymerization techniques, in particular using reversible addition-fragmentation chain transfer (RAFT) in the presence of xanthates (Macromolecular Design by Exchange of Xanthates (MADIX)), atom transfer radical polymerization (ATRP), iodine transfer polymerization (ITP), reversible chain transfer catalyzed radical polymerization (RCTP), tellurium mediated radical polymerization (TERP), cobalt mediated radical polymerization (CoMP) or reversible coordination mediated polymerization (RCMP). These different techniques are described in Polymer Chemistry 2018, 9, 4947-4967 and the references cited therein. Thus, the method of the present invention results in copolymers having at least thioester bonds that are easily degradable.

[0089] The method of implementing a cyclic monomer (I) with at least one monomer containing ethylenic unsaturation (II) in the presence of a radical polymerization initiator also allows for the consumption of a portion of the cyclic monomer (I) during polymerization without ring-opening. The copolymer thus obtained contains, in addition to the ring-opened thioester bond, cyclic monomer (I) units with orthodithioester and / or thioacetal bonds. These cyclic monomer units (I) with orthodithioester and / or thioacetal bonds have the advantage that they are sensitive to chemical attack and therefore potentially decomposable. The degradable copolymers obtainable by carrying out the process according to the invention are novel per se and therefore constitute a second object of the invention.

[0090] A second object of the present invention is therefore also a copolymer, preferably a degradable copolymer, which comprises at least a thioester bond and which, in the presence of a radical polymerization initiator, (i) a compound of formula (I) [ka]

[0091] During the ceremony, -X is an oxygen atom or a sulfur atom, -R 1 , R 2 , R 3 and R 4 are each independently a hydrogen atom, a halogen atom, an alkyl group, a haloalkyl group, an optionally substituted phenyl group, a cyano group (CN), an optionally substituted alkyl-phenyl group, an optionally substituted haloalkyl-phenyl group, a carboxylic acid group (COOH), R 5 CO represents an alkyl group 2 R 5 , phosphonic acid group (PO(OH) 2 ), R 6a represents a hydrogen atom or an alkyl group, R 6b Phosphonate group P(O)(OR) represents an alkyl group 6a )(OR 6b ), sulfonic acid group (SO 3 H), R 7 represents an alkyl or haloalkyl group; 3 R 7 , R 8a and R 8b each independently represents a hydrogen atom or an alkyl group, or together form an alkyl group, an amide group, C(O)NR 8a R 8b represents a group selected from At least one cyclic monomer selected from thionolactides of formula (I) (ii) a compound of formula (II) [ka]

[0092] During the ceremony, -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 group, a fluorine atom or a chlorine atom, -R 12 is a hydrogen atom or one of the following groups: *Alkyl group *Haloalkyl group *Optionally substituted aryl groups, *Optionally substituted alkyl-aryl groups, *Imidazolyl group *Alkyl imidazolium group, *Carbazolyl group, * a group of formula (III) [ka]

[0093] where the asterisk (*) represents the anchor point of the group of formula (III) to a carbon atom of the compound of formula (II), and R 13 and R 14 are the same or different and represent a hydrogen atom, an alkyl group, an optionally substituted alkylaryl group, an optionally substituted aryl group, or a glycidyl group, or R 13 and R 14 together with the nitrogen atom and the carbon atom of the group of formula (III) to which they are attached form a heterocarbocycle containing 4 to 7 carbon atoms (including the carbon atom bearing an oxygen atom); Group of formula (III) *-OC(O)R 15 A group, wherein R 15represents an alkyl group, a haloalkyl group, an optionally substituted alkyl-aryl group, or an optionally substituted aryl group; -OC(O)R 15 basis *-C(O)OR 16 A group, wherein R 16 represents an alkyl group, a haloalkyl group, an optionally substituted alkyl-aryl group or an optionally substituted aryl group; -C(O)OR 16 basis *Phosphonic acid group (PO(OH) 2 ), *Phosphonate ester group P(O)(OR 17a )(OR 17b ) in which R 17a represents a hydrogen atom or an alkyl group, R 17b represents an alkyl group, and a phosphonate group P(O)(OR 17a )(OR 17b ) *Sulfonic acid group (SO 3 H), *Sulfonic acid ester group SO 3 R 18 wherein R 18 represents an alkyl group or a haloalkyl group, and a sulfonate group SO 3 R 18 , and *Amide group C(O)NR 19a R 19b wherein R 19a and R 19b represent, independently of one another, a hydrogen atom or an alkyl group or together form an alkyl group, an amide group C(O)NR 19a R 19b represents a group selected from at least one monomer containing ethylenic unsaturation selected from monomers of formula (II), It is characterized by being produced from radical polymerization by ring-opening of the formula:

[0094] The preferences given above in relation to the first object of the invention with regard to the monomers of formulae (I) and (II) also apply to the second object of the invention.

[0095] According to a particularly preferred embodiment of the invention, the copolymer results from the polymerization of thionolactide (I-1) with vinyl acetate, styrene, tert-butyl acrylate, methyl methacrylate or vinyl pivalate. According to a preferred embodiment of the second object of the present invention, the copolymer, preferably the degradable copolymer, is a random copolymer.

[0096] According to the invention, the copolymer, preferably the degradable copolymer, preferably has a number average molar mass of about 2,000 to 200,000 g / mol, even more preferably of about 5,000 to 100,000 g / mol. The polymolecular index of the polymers according to the present invention, preferably degradable polymers, is preferably in the range of 1.2-4, even more preferably 1.4-3.

[0097] The level of thioester bonds in the backbone of the degradable copolymers according to the invention is preferably at least 2% by number, preferably 2-20% by number, even more preferably 5-15% by number, relative to the total number of bonds in the backbone. The copolymers may further contain orthodithioester and / or thioacetal linkages that are also degradable.

[0098] According to the present invention, the backbone of a copolymer is meant to be the longest bond linkage, ie, not including the attachment of side substituents.

[0099] Due to their degradable nature, the copolymers according to the invention can be useful in all kinds of industries, for example in the biomedical field, agriculture, cosmetics, oil extraction, detergents, salting out and packaging of active products.

[0100] If the copolymers of the present invention exhibit little or no degradability, they may also be useful in the medical field, particularly in dental fillings, or in any type of field where it is desirable to reduce shrinkage associated with polymerization.

[0101] Furthermore, a third object of the present invention is the use of at least one ionolactide having formula (I) as defined in the first object of the present invention as a precursor monomer in a radical polymerization.

[0102] Radical polymerization is as defined in the first object of the present invention. Some thionolactides having formula (I) are novel per se and constitute a fourth object of the present invention.

[0103] A fourth object of the invention is therefore a thiolactide for carrying out the process defined in the first object of the invention, said thiolactide having formula (I') below, [ka] During the ceremony, -X, R 1 , R 2 , R 3 and R 4 is as defined in the first object of the present invention, - excluding the thionolactides (I-1) and (I-2) defined in the present invention, It has the formula (I').

[0104] Preferably, the thionolactide of formula (I') is selected from the thionolactides of formulae (I-3) to (I-14) described in the present invention.

[0105] The lactide precursors of the thionolactides of formula (I) or (I') described in the present invention can be obtained by dimerizing the corresponding α-hydroxy acids or, in the case of compounds (I-13) and (I-14), by reacting α-hydroxyisobutyric acid with chloroacetyl chloride or chloropropyl. Single or double thionation of lactide can be achieved by the reaction of P 4 S 10 and in the presence of hexamethyldisiloxane (HMDSO). The accompanying drawings illustrate the invention. [Brief description of the drawings]

[0106] [Figure 1] FIG. 2 shows the chemical degradation of polymer CP2 according to the present invention. [Diagram 2] FIG. 2 shows the chemical degradation of polymer CP6 according to the present invention. [Diagram 3] FIG. 1 shows the crystal structure of compound (I-13) used in the method according to the present invention. [Figure 4] FIG. 2 shows the chemical degradation of polymer CP8 according to the invention. [Diagram 5] FIG. 1 shows the crystal structure of compound (I-14) used in the method according to the present invention. [Figure 6] Figure 1 shows the chemical degradation of polymer CP10 according to the invention Further features and advantages of the present invention will become apparent from the description of the examples given below, to which the present invention is not limited. EXAMPLES

[0107] The analysis by steric exclusion chromatography was carried out using an equipment 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.

[0108] Example 1: Synthesis of degradable copolymer CP1 based on styrene and thionolactide of formula (I-1) by the method of the present invention 1.1 First step: synthesis of thionolactide of formula (I-1) P 4 S 10(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 equipped with an overhead condenser. The mixture obtained was heated under reflux for 48 hours. The reaction medium was then cooled to room temperature and 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 (8 / 2 cyclohexane / ethyl acetate eluent). The thionolactide was recrystallized four times to obtain crystals with a yield of 33% (1.8 g). The crystals obtained were then heated at 60°C and 10°C for 2 h. -2 It was sublimed at a pressure of 10000000 mbar before being used in polymerization. 1 H NMR (CDCl 3 ,300 MHz)δ(ppm):5.06(q,1H),4.98(q,1H),1.79(d,3H),1.76(d,3H). 13 C NMR (CDCl 3 ,126 MHz)δ(ppm):211.4,167.5,78.4,75.1,19.3,15.5. 1.2 Second step: Synthesis of poly(styrene-co-thionolactide) copolymer CP1 A solution was formed by mixing 6 mg (0.025 mmol) of azobis(cyanocyclohexane) (VAZO-88), 0.08 g (0.5 mmol) of thionolactide (I-1) obtained in the previous step, 0.468 g (4.5 mmol) of styrene, and 10 mg of naphthalene as an internal standard. Thionolactide (monomer of formula (I-1)) accounts for 10% (molar basis) relative to styrene (monomer of formula (II)). The solution was transferred to a carious tube sealed under vacuum after three degassing cycles. The tube was then placed in an oil bath at 100 °C for 5 h. The polymerization was stopped by rapid cooling. After opening the tube, a portion of the solution was transferred to an NMR tube to determine the conversion of thionolactide (I-1) after 5 h of reaction.

[0109] The conversion to monomers was confirmed by hydrogen nuclear magnetic resonance ( 1H NMR). To do this, the signal at 7.8 ppm of naphthalene as an internal standard, corresponding to 1, was integrated and compared with the signal at 5.10 to 4.95 ppm, corresponding to the two hydrogen atoms of thionolactide (I-1), and compared with the result of the integration at a reaction time equal to 0 hours. The conversion of thionolactide (I-1) after a reaction time of X hours can therefore be determined according to the following equation 1:

[0110]

number

[0111] Hydrogen nuclear magnetic resonance ( 1 The conversion to monomers, determined by H NMR, was 58% for thionolactide (I-1) and 82% for styrene. The residual monomers were evaporated and the number-average molar mass (Mn) of the copolymer CP1, as well as the polymolecularity index (Mw / Mn), were determined by steric exclusion chromatography (eluent: tetrahydrofuran THF) using a calibration curve based on PMMA: Mn=13200 g / mol; Mw / Mn=2.3.

[0112] Example 2: Synthesis of degradable copolymer CP2 based on tert-butyl acrylate and thionolactide of formula (I-1) by the method of the present invention

[0113] 5.3 mg (0.022 mmol) of azobis(cyanocyclohexane) (VAZO-88), 0.07 g (0.44 mmol) of thionolactide (I-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 (I-1)) represents 10% (molar basis) relative to tert-butyl acrylate (monomer of formula (II)). The solution was transferred to a carious tube sealed under vacuum after three degassing cycles. The tube was then placed in an oil bath at 100° C. for 5 hours. The polymerization was stopped by rapid cooling. After opening the tube, a portion of the solution was transferred to an NMR tube to determine the conversion of thionolactide (I-1) after 5 hours of reaction.

[0114] As described in Example 1, hydrogen nuclear magnetic resonance ( 1 The conversion to monomers, determined by H NMR, was 34% for thionolactide (I-1) and 33% for tert-butyl acrylate. Residual monomers were evaporated and the number-average molar mass (Mn) as well as the multimolecular weight index (Mw / Mn) of the poly(tert-butyl acrylate-co-thionolactide) copolymer CP2 were determined by steric exclusion chromatography (eluent: THF) using a calibration curve based on PMMA: Mn=8000 g / mol; Mw / Mn=1.7.

[0115] Example 3: Synthesis of degradable copolymer CP3 based on methyl methacrylate and thionolactide of formula (I-1) by the method of the present invention 6.1 mg (0.025 mmol) of azobis(cyanocyclohexane) (VAZO-88), 0.08 g (0.5 mmol) of thionolactide (I-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 (I-1)) accounts for 10% (mol) relative to methyl methacrylate (monomer of formula (II)). The solution was transferred to a carious tube sealed under vacuum after three degassing cycles. The tube was then placed in an oil bath at 100° C. for 5 hours. The polymerization was stopped by rapid cooling. After opening the tube, a portion of the solution was transferred to an NMR tube to determine the conversion of thionolactide (I-1) after 5 hours of reaction.

[0116] As described in Example 1, hydrogen nuclear magnetic resonance ( 1 The conversion to monomers, determined by H NMR, was 10% for thionolactide (I-1) and 64% for methyl methacrylate. Residual monomers were evaporated and the number-average molar mass (Mn) of the poly(methyl methacrylate-co-thionolactide) copolymer CP3, as well as the polymolecularity index (Mw / Mn), were determined by steric exclusion chromatography (eluent: THF) using a calibration curve based on PMMA: Mn=7000 g / mol; Mw / Mn=1.9.

[0117] Example 4: Synthesis of degradable copolymer CP4 based on vinyl pivalate and thionolactide of formula (I-1) by the method of the present invention A solution was formed by mixing 5.4 mg (0.022 mmol) of azobis(cyanocyclohexane) (VAZO-88), 0.07 g (0.44 mmol) of thionolactide (I-1) obtained in Example 1, 0.504 g (3.9 mmol) of vinyl pivalate, and 10 mg of naphthalene as an internal standard. Thionolactide (monomer of formula (I-1)) accounts for 10% (molar basis) relative to vinyl pivalate (monomer of formula (II)). The solution was transferred to a sealed carious tube 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, a portion of the solution was transferred to an NMR tube to determine the conversion of thionolactide (I-1) after 16 hours of reaction.

[0118] As described in Example 1, hydrogen nuclear magnetic resonance ( 1 The conversion to monomers, determined by H NMR, was 100% for thionolactide (I-1) and 64% for vinyl pivalate. Residual monomers were evaporated and the number-average molar mass (Mn) and the multimolecular weight index (Mw / Mn) of the poly(vinyl pivalate-co-thionolactide) copolymer CP4 were determined by steric exclusion chromatography (eluent: THF) using a calibration curve based on PMMA: Mn=12100 g / mol; Mw / Mn=2.1.

[0119] Example 5: Chemical Degradation of Degradable Copolymer CP2 Based on tert-Butyl Acrylate and Thionolactide of Formula (I-1) 10 mg of copolymer CP2 from Example 2 was diluted in 1 mL of THF and 1 mL of bleach solution (NaOCl aqueous solution containing 11-15% active chlorine) was added. The resulting mixture was left stirring in a sealed tube at room temperature for 14 days. The solvent was evaporated under reduced pressure, and the residue was then dissolved in THF and analyzed by steric exclusion chromatography.

[0120] Figure 1 shows the behavior of CP2 in terms of the relative Δn value (i.e. the difference between the refractive index of the analyzed sample and that of the solvent) as a function of the retention time (min) before contact with the bleach (CP2 in THF, Mn = 8000 g / mol, Mw / Mn = 1.7, Figure 1a), the residue obtained after contacting CP2 with the bleach (Mn = 2100 g / mol, Mw / Mn = 1.5, Figure 1b), and CP2 after dilution with THF and standing at room temperature for 30 days (Mn = 6400 g / mol, Mw / Mn = 2.0, Figure 1c).

[0121] After degradation of the copolymer CP2 by bleach, the molar mass distribution appears to be strongly shifted towards the lower molar mass range compared to the pretreated copolymer, demonstrating backbone degradation due to the presence of thioester bonds.

[0122] Example 6: Synthesis of degradable copolymer CP5 based on n-butyl acrylate and thionolactide of formula (I-1) by the method of the present invention 4.3 mg (0.022 mmol) of azobis(isobutyronitrile) (AIBN), 0.07 g (0.44 mmol) of thionolactide (I-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 (I-1)) accounts for 10% (molar basis) relative to n-butyl acrylate (monomer of formula (II)). The solution was transferred to a carious tube 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, a portion of the solution was transferred to an NMR tube to determine the conversion of thionolactide (I-1).

[0123] As described in Example 1, hydrogen nuclear magnetic resonance ( 1The conversion to monomers, determined by H NMR, was 41% for thionolactide (I-1) and 87% for n-butyl acrylate. Residual monomers were evaporated and the number-average molar mass (Mn) as well as the multimolecular weight index (Mw / Mn) of the poly(n-butyl acrylate-co-thionolactide) copolymer CP5 were determined by steric exclusion chromatography (eluent: THF) using a calibration curve based on PMMA: Mn=98000 g / mol; Mw / Mn=1.7.

[0124] Example 7: Synthesis of degradable copolymer CP6 based on tert-butyl acrylate and dithionolactide of formula (I-2) by the method of the present invention 7.1 First step: synthesis of dithionolactide of formula (I-2) P 4 S 10 (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 equipped with an overhead condenser. The resulting mixture was heated under reflux for 48 h. The reaction medium was then cooled to room temperature and 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: 8 / 2 cyclohexane / ethyl acetate). Dithionolactide (I-2) was recrystallized four times to obtain crystals with a yield of 2% (0.1 g). The crystals obtained were then heated at 60 °C and 10 °C. -2 It was sublimed at a pressure of 10000000 mbar before being used in polymerization.

[0125] 1 H NMR (CDCl 3 ,300 MHz)δ(ppm):5.05(q,6.3 Hz,2H),1.8(d,6.3 Hz,6H). 13 C NMR (CDCl 3 ,126 MHz)δ(ppm):211.2,78.6,19.5. 7.2 Second step: Synthesis of degradable copolymer CP6 based on tert-butyl acrylate and dithionolactide of formula (I-2) according to the method of the present invention

[0126] 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% (molar basis) relative to tert-butyl acrylate (monomer of formula (II)). The solution was transferred to a carious tube sealed under vacuum after three degassing cycles. The tube was then placed in an oil bath at 100 °C for 5 hours. The polymerization was stopped by rapid cooling. After opening the tube, a portion of the solution was transferred to an NMR tube to determine the conversion of dithionolactide (I-2) after 5 hours of reaction.

[0127] The conversion to monomers was confirmed by hydrogen nuclear magnetic resonance ( 1 H NMR (H NMR). To do this, the signal at 7.8 ppm of naphthalene as internal standard, corresponding to 1, was integrated and compared with the signal at 5.0-5.1 ppm, corresponding to the two hydrogen atoms of dithionolactide (I-2), and compared with the result of the integration at a reaction time equal to 0 hours. The conversion of dithionolactide (I-2) after a reaction time of X hours can therefore be determined according to the following equation 2:

[0128]

number

[0129] Hydrogen nuclear magnetic resonance ( 1The conversion to monomers, determined by H NMR, was 100% for dithionolactide (I-2) and 98% for tert-butyl acrylate. Residual monomers were evaporated and the number-average molar mass (Mn) as well as the multimolecular weight index (Mw / Mn) of the poly(tert-butyl acrylate-co-thionolactide) copolymer CP6 were determined by steric exclusion chromatography (eluent: THF) using a calibration curve based on PMMA: Mn=28300 g / mol; Mw / Mn=2.5.

[0130] Example 8: Chemical Degradation of Degradable Copolymer CP6 Based on tert-Butyl Acrylate and Dithionolactide of Formula (I-2) 10 mg of copolymer CP6 from Example 7 was diluted in 1 mL of THF and 1 mL of bleach solution (NaOCl aqueous solution containing 11-15% active chlorine) was added. The resulting mixture was left stirring in a sealed tube at room temperature for 14 days. The solvent was evaporated under reduced pressure, and the residue was then dissolved in THF and analyzed by steric exclusion chromatography.

[0131] 10 mg of copolymer CP6 from Example 7 was diluted in 1 mL of THF and 1 mL of isopropylamine solution was added. The resulting mixture was left stirring at room temperature in a sealed tube for 30 days. The solvent and isopropylamine were evaporated under reduced pressure, and the residue was then dissolved in THF and analyzed by steric exclusion chromatography.

[0132] Figure 2 shows the behavior of CP6 in terms of the relative Δn value (i.e. the difference between the refractive index of the analyzed sample and that of the solvent) as a function of the retention time (min) before contact with bleach and isopropylamine (Mn=28300 g / mol; Mw / Mn=2.5; Figure 2a), the residue obtained after contacting CP6 with bleach (Mn=7700 g / mol, Mw / Mn=3.5; Figure 2b), and the residue obtained after contacting CP6 with isopropylamine (Mn=8200 g / mol, Mw / Mn=2.8; Figure 2c).

[0133] After degradation of the copolymer CP6 by either bleach or isopropylamine, the molar mass distribution appears to be strongly shifted towards the lower molar mass range compared to the pretreated copolymer, demonstrating backbone degradation due to the presence of thioester bonds.

[0134] Example 9: Synthesis of degradable copolymer CP7 based on methyl methacrylate and dithionolactide of formula (I-2) by the method of the present invention 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% (molar basis) relative to methyl methacrylate (monomer of formula (II)). The solution was transferred to a carious tube sealed under vacuum after three degassing cycles. The tube was then placed in an oil bath at 100 °C for 5 hours. The polymerization was stopped by rapid cooling. After opening the tube, a portion of the solution was transferred to an NMR tube to determine the conversion of dithionolactide (I-2) after 5 hours of reaction.

[0135] As described in Example 7.2, hydrogen nuclear magnetic resonance ( 1 The conversion to monomers, determined by H NMR, was 20% for dithionolactide (I-2) and 80% for methyl methacrylate. Residual monomers were evaporated and the number-average molar mass (Mn) as well as the multimolecular weight index (Mw / Mn) of poly(methyl methacrylate-co-dithionolactide) copolymer CP7 were determined by steric exclusion chromatography (eluent: THF) using a calibration curve based on PMMA: Mn=15000 g / mol; Mw / Mn=2.7.

[0136] Example 10: Synthesis of thionolactide of formula (I-3) P 4 S 10(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 added to a two-neck flask equipped with an overhead condenser. The resulting mixture was heated under reflux for 5 hours. The reaction medium was then cooled to room temperature and the solvent was evaporated. The product was first purified by column chromatography (dichloromethane eluent) and then the collected fractions were purified again by column chromatography (50 g silica gel, eluent: 30% ethyl ether / 70% petroleum ether) giving a yield of 20% (1.1 g). 1 H NMR (CDCl 3 ,300 MHz)δ(ppm):5.2(s,4H). 13 C NMR (CDCl 3 ,126 MHz)δ(ppm):206,165,78,73.

[0137] Example 11: Synthesis of degradable copolymer CP8 based on tert-butyl acrylate and thionolactide of formula (I-13) by the method of the present invention 11.1 Step 1: Synthesis of 3,3-dimethylglycolide 9.2 g (88.5 mmol) of alpha-hydroxyisobutyric acid and 10 g of chloroacetyl chloride (88.5 mmol) were added to 20 mL of anhydrous acetonitrile in a two-neck flask equipped with an overhead condenser. The mixture was heated to 80° C. overnight with stirring. After cooling to room temperature, the reaction mixture was diluted with 200 mL of acetonitrile and 17.9 g of triethylamine (177 mmol) was added dropwise. The resulting solution was then heated to 80° C. for 6 hours. After filtration, the product was obtained by evaporating the solvent in 40% yield (5.1 g).

[0138] 1 H NMR (CDCl 3 ,300 MHz):δ(ppm):1.67(s,6H);5.01(s,2H). 13 C NMR (CDCl 3,126 MHz)δ(ppm):167,164,75,73,24. 11.2 Second step: Synthesis of thionolactide 3,3-dimethylthioglycolide of formula (I-13) P 4 S 10 (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 into a two-necked flask equipped with an overhead condenser, the whole of which was inerted by bubbling argon. The mixture obtained was heated under reflux for 24 hours. The reaction medium was then cooled to room temperature and the solvent was then evaporated. The product was first purified by column chromatography (dichloromethane eluent) and then the collected fractions were purified again by column chromatography (50 g silica gel, eluent: 30% ethyl ether / 70% petroleum ether), giving a yield of 20% (1.8 g).

[0139] 1 H NMR (CDCl 3 ,300MHz):5.2ppm(s,2H),1.76ppm(s,6H). 13 CNMR(CDCl 3 ,126MHz):206.2,167.7,82.5,73.8,25.2. FIG. 3 shows the crystal structure of thionolactide (I-13). 11.3 Third step: Synthesis of degradable copolymer CP8 based on tert-butyl acrylate and thionolactide of formula (I-13) by the method of the present invention

[0140] 5.3 mg (0.022 mmol) of azobis(cyanocyclohexane) (VAZO-88), 0.07 g (0.44 mmol) of thionolactide (I-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 (I-13)) accounts for 10% (molar basis) relative to tert-butyl acrylate (monomer of formula (II)). The solution was transferred to a carious tube sealed under vacuum after three degassing cycles. The tube was then placed in an oil bath at 100° C. for 5 hours. The polymerization was stopped by rapid cooling. After opening the tube, a portion of the solution was transferred to an NMR tube to determine the conversion of thionolactide (I-13) after 5 hours of reaction.

[0141] The conversion to monomers was confirmed by hydrogen nuclear magnetic resonance ( 1 H NMR). To do this, the signal at 7.8 ppm from naphthalene as internal standard, corresponding to 1, was integrated and compared with the signal at 5.3-5.1 ppm corresponding to two hydrogen atoms from thionolactide (I-13) and compared with the result of integration at a reaction time equal to 0 hours. The conversion of thionolactide (I-13) after a reaction time of X hours can therefore be determined according to the following equation 3:

[0142]

number

[0143] Hydrogen nuclear magnetic resonance ( 1 The conversion to monomers, determined by H NMR, was 44% for thionolactide (I-13) and 82% for tert-butyl acrylate. Residual monomers were evaporated and the number-average molar mass (Mn) as well as the multimolecular weight index (Mw / Mn) of the poly(tert-butyl acrylate-co-thionolactide) copolymer CP8 were determined by steric exclusion chromatography (eluent: THF) using a calibration curve based on PMMA: Mn=13800 g / mol; Mw / Mn=2.4.

[0144] Example 12: Chemical Degradation of Degradable Copolymer CP8 Based on tert-Butyl Acrylate and Thionolactide of Formula (I-13) 10 mg of copolymer CP8 from Example 11.3 was diluted in 1 mL of THF and 1 mL of bleach solution (NaOCl aqueous solution containing 11-15% active chlorine) was added. The resulting mixture was left stirring in a sealed tube at room temperature for 14 days. The solvent was evaporated under reduced pressure and the residue was then dissolved in THF and analyzed by steric exclusion chromatography.

[0145] Figure 4 shows the behavior of CP8 before degradation in terms of the relative Δn value (i.e. the difference between the refractive index of the analyzed sample and that of the solvent) as a function of retention time (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).

[0146] After degradation of the copolymer CP8 by bleaching, the molar mass distribution appears to be strongly shifted towards the lower molar mass range compared to the pretreated copolymer, demonstrating backbone degradation due to the presence of thioester bonds.

[0147] Example 13: Synthesis of degradable copolymer CP9 based on methyl methacrylate and thionolactide of formula (I-13) by the method of the present invention 6.1 mg (0.025 mmol) of azobis(cyanocyclohexane) (VAZO-88), 0.08 g (0.5 mmol) of thionolactide (I-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 (I-13)) accounts for 10% (molar basis) relative to methyl methacrylate (monomer of formula (II)). The solution was transferred to a carious tube sealed under vacuum after three degassing cycles. The tube was then placed in an oil bath at 100° C. for 5 hours. The polymerization was stopped by rapid cooling. After opening the tube, a portion of the solution was transferred to an NMR tube to determine the conversion of thionolactide (I-13) after 5 hours of reaction.

[0148] As described in Example 11.2, hydrogen nuclear magnetic resonance ( 1 The conversion to monomers, determined by H NMR, was 25% for thionolactide (I-13) and 90% for methyl methacrylate. Residual monomers were evaporated and the number-average molar mass (Mn) of the poly(methyl methacrylate-co-thionolactide) copolymer CP9, as well as the polymolecularity index (Mw / Mn), were determined by steric exclusion chromatography (eluent: THF) using a calibration curve based on PMMA; Mn=13900 g / mol; Mw / Mn=2.0.

[0149] Example 14: Synthesis of degradable copolymer CP10 based on tert-butyl acrylate and thionolactide of formula (I-14) by the method of the present invention 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) were added to 20 mL of anhydrous acetonitrile in a two-neck flask equipped with an overhead condenser. The mixture was heated to 80° C. overnight with stirring. After cooling to room temperature, the reaction mixture was diluted with 200 mL of acetonitrile, and then 15.9 g of triethylamine (157.5 mmol) was added dropwise. The resulting solution was then heated to 80° C. for 6 hours. After filtration, the product was obtained by evaporating the solvent in 40% yield (4.4 g).

[0150] 1 H NMR (CDCl 3 ,300 MHz)δ(ppm):1.68(m,9H);5.09(q,7.2 Hz,1H). 13 C NMR (CDCl 3 ,126 MHz)δ(ppm):168.8,166.8,80.7,73.1,26.4,25.4,17.6. 14.2 Second step: Synthesis of thionolactide 3,3,6-trimethylthioglycolide of formula (I-14) P 4 S 10 (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 into a two-necked flask containing an overhead coolant, the entirety of which was inertized by bubbling argon through it. The mixture obtained was heated under reflux for 24 hours. The reaction medium was then cooled to room temperature and the solvent was then evaporated. The product was first purified by column chromatography (dichloromethane eluent) and then the collected fractions were purified again by column chromatography (50 g silica gel, eluent: 20% ethyl ether / 80% petroleum ether), giving a yield of 25% (0.8 g).

[0151] 1 H NMR (CDCl 3,300MHz):5.2(q,6.6Hz,1H),1.87(d,6.6Hz,3H),1.79(s,6H). 13 CNMR(CDCl 3 ,126MHz):211.4,169.0,83.2,79.6,24.7,21.5. FIG. 5 shows the crystal structure of thiolactide (I-14).

[0152] 14.3 Third step: Synthesis of degradable copolymer CP10 based on tert-butyl acrylate and thionolactide of formula (I-14) by the method of the present invention 5 mg (0.02 mmol) of azobis(cyanocyclohexane) (VAZO-88), 0.07 g (0.40 mmol) of thionolactide (I-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. Thionolactide (monomer of formula (I-14)) accounts for 10 mol% relative to tert-butyl acrylate (monomer of formula (II)). The solution was transferred to a carious tube sealed under vacuum after three degassing cycles. The tube was then placed in an oil bath at 100 °C for 5 h. The polymerization was stopped by rapid cooling. After opening the tube, a portion of the solution was transferred to an NMR tube to determine the conversion of thionolactide (I-14) after 5 h of reaction.

[0153] The conversion to monomers was confirmed by hydrogen nuclear magnetic resonance ( 1 H NMR). To do this, the signal at 7.8 ppm from naphthalene as internal standard, corresponding to 1, was integrated and compared with the signal at 5.1-4.9 ppm corresponding to two hydrogen atoms from thionolactide (I-14) and compared with the result of integration at a reaction time equal to 0 hours. The conversion of thionolactide (I-14) after a reaction time of X hours can therefore be determined according to the following equation 4:

[0154]

number

[0155] Hydrogen nuclear magnetic resonance ( 1 The conversion to monomers, as determined by H NMR, was 26% for thionolactide (I-14) and 52% for tert-butyl acrylate. Residual monomers were evaporated and the number-average molar mass (Mn) as well as the multimolecular weight index (Mw / Mn) of the poly(tert-butyl acrylate-co-thionolactide) copolymer CP10 were determined by steric exclusion chromatography (eluent: THF) using a calibration curve based on PMMA: Mn=13500 g / mol; Mw / Mn=4.2.

[0156] Example 15: Chemical Degradation of Degradable Copolymer CP10 Based on tert-Butyl Acrylate and Thionolactide of Formula (I-14) 10 mg of copolymer CP10 from Example 14.3 was diluted in 1 mL of THF and 1 mL of bleach solution (NaOCl aqueous solution containing 11-15% active chlorine) was added. The resulting mixture was left stirring in a sealed tube at room temperature for 14 days. The solvent was evaporated under reduced pressure and the residue was then dissolved in THF and analyzed by steric exclusion chromatography.

[0157] Figure 6 shows the behavior of CP10 in terms of the relative Δn value (i.e. the difference between the refractive index of the analyzed sample and that of the solvent) as a function of the retention time (min) before contact with the bleach (CP10 in THF, Mn = 13500 g / mol; Mw / Mn = 3.8, Figure 6a) and of the residue obtained after contacting CP10 with the bleach (Mn = 5700 g / mol, Mw / Mn = 1.9, Figure 6b).

[0158] After degradation of the copolymer CP10 by bleach, the molar mass distribution appears to be strongly shifted towards the lower molar mass range compared to the pretreated copolymer, demonstrating backbone degradation due to the presence of thioester bonds.

[0159] Example 16: Synthesis of degradable copolymer CP11 based on methyl methacrylate and thionolactide of formula (I-14) by the method of the present invention 5.6 mg (0.023 mmol) of azobis(cyanocyclohexane) (VAZO-88), 0.08 g (0.46 mmol) of thionolactide (I-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 (I-14)) accounts for 10% (molar basis) relative to methyl methacrylate (monomer of formula (II)). The solution was transferred to a carious tube sealed under vacuum after three degassing cycles. The tube was then placed in an oil bath at 100 °C for 5 hours. The polymerization was stopped by rapid cooling. After opening the tube, a portion of the solution was transferred to an NMR tube to determine the conversion of thionolactide (I-14) after 5 hours of reaction.

[0160] As described in Example 14.3, hydrogen nuclear magnetic resonance ( 1 The conversion to monomers, determined by H NMR, was 15% for thionolactide (I-14) and 28% for methyl methacrylate. Residual monomers were evaporated and the number-average molar mass (Mn) of the poly(methyl methacrylate-co-thionolactide) copolymer CP11, as well as the polymolecularity index (Mw / Mn), were determined by steric exclusion chromatography (eluent: THF) using a calibration curve based on PMMA: Mn=2400 g / mol; Mw / Mn=1.4.

[0161] Example 17: Synthesis of degradable copolymer CP12 based on styrene and thionolactide of formula (I-14) by the method of the present invention 5 mg (0.020 mmol) of azobis(cyanocyclohexane) (VAZO-88), 0.07 g (0.4 mmol) of thionolactide (I-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 (I-14)) accounts for 10% (molar basis) relative to styrene (monomer of formula (II)). The solution was transferred to a carious tube sealed under vacuum after three degassing cycles. The tube was then placed in an oil bath at 100 °C for 5 hours. The polymerization was stopped by rapid cooling. After opening the tube, a portion of the solution was transferred to an NMR tube to determine the conversion of thionolactide (I-14) after 5 hours of reaction.

[0162] As described in Example 14.3, hydrogen nuclear magnetic resonance ( 1 The conversion to monomers, determined by H NMR, was 26% for thionolactide (I-14) and 46% for styrene. The residual monomers were evaporated and the number-average molar mass (Mn) of the copolymer CP12, as well as the polymolecularity index (Mw / Mn), were determined by steric exclusion chromatography (eluent: THF tetrahydrofuran) with a calibration curve based on PMMA: Mn=3700 g / mol; Mw / Mn=3.2.

Claims

1. A method for preparing at least one copolymer, preferably at least one degradable copolymer, wherein the method comprises at least one step of radical polymerization by ring opening of at least one cyclic monomer and at least one monomer comprising an ethylenically unsaturated monomer in the presence of a radical polymerization initiator, (i) The cyclic monomer is of the following formula (I), 【Chemistry 1】 During the ceremony, -X is an oxygen atom or a sulfur atom, -R １ , R ２ , R ３ and R ４ are, independently of one another, a hydrogen atom, a halogen atom, an alkyl group, a haloalkyl group, an optionally substituted phenyl group, a cyano group, an optionally substituted alkyl-phenyl group, an optionally substituted haloalkyl-phenyl group, a carboxylic acid group, R ５ where R represents an alkyl group, an ester group CO ２ R ５ , a phosphonic acid group, R ６ａ represents a hydrogen atom or an alkyl group, and R ６ｂ represents an alkyl group, a phosphonic acid ester group P(O)(OR ６ａ )(OR ６ｂ ), a sulfonic acid group, R ７ represents an alkyl group or a haloalkyl group, a sulfonic acid ester group SO ３ R ７ , and R 8ａ and R ８ｂ are, independently of one another, a hydrogen atom or an alkyl Amide groups C(O)NR that represent a group or, together with it, form an alkyl group. ８ａ R ８ｂ Represents a base selected from, Selected from the thionolactides of formula (I), (ii) A monomer containing ethylenically unsaturated monomer is defined by the following formula (II): 【Chemistry 2】 During the ceremony, -R ９ This represents a hydrogen atom or a fluorine atom, -R １０ This represents a hydrogen atom or a fluorine atom, -R １１ This represents a hydrogen atom, alkyl group, fluorine atom, or chlorine atom. R １２ is a hydrogen atom, or the following groups: *Alkyl *Halor *Substituted aryl groups in some cases, *Substituted alkyl-aryl groups may be used. *Imidazolyl group *Alkylimidazolium group, *Carbazoyl group, *The basis of the following formula (III), 【Transformation 3】 In the formula, the asterisk (*) represents the anchor point of the group in formula (III) to the carbon atom of the compound in formula (II), R １３ and R １４ , either identical or different, represents a hydrogen atom, an alkyl group, optionally a substituted alkyl-aryl group, optionally a substituted aryl group, 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, they form a heterocarbon ring containing 4 to 7 carbon atoms. Based on equation (III), *-OC(O)R １５ It is a base, in the formula R １５ -OC(O)R represents an alkyl group, a haloalkyl group, an optionally substituted alkyl-aryl group, or an optionally substituted aryl group. １５ basis -C(O)OR １６ It is a base, in the formula R １６ -C(O)OR represents an alkyl group, a haloalkyl group, an optionally substituted alkyl-aryl group, or an optionally substituted aryl group. １６ basis *Phosphonic acid group, *Phosphonic acid ester group P(O)(OR) １７ａ ) ( OR １７ｂ ) and in the formula, R １７ａ R represents a hydrogen atom or an alkyl group. １７ｂ P(O)(OR) represents an alkyl group, a phosphonic acid ester group. １７ａ ) ( OR １７ｂ ) *Sulfonic acid group, *Sulfonic acid ester group SO ３ R １８ And in the formula, R １８ SO represents an alkyl group or haloalkyl group, a sulfonic acid ester group. ３ R １８ , and * Amide group C(O)NR １９ａ R １９ｂ And in the formula, R １９ａ and R １９ｂ These are amide groups C(O)NR, which independently represent a hydrogen atom or an alkyl group, or together form an alkyl group. １９ａ R １９ｂ Represents a base selected from, Selected from the monomers of formula (II), A method for preparing at least one copolymer, preferably at least one biodegradable copolymer, characterized by the above.

2. R １ , R ２ , R ３ and R ４ The method according to claim 1, characterized in that each independently represents a group selected from a hydrogen atom, a halogen atom, an alkyl group, a haloalkyl group, an optionally substituted phenyl group, an optionally substituted alkyl-phenyl group, and an optionally substituted haloalkyl-phenyl group.

3. *R １ = H or CH ３ , *R ２ = H, CH ３ , C ６ H ５ , CF ３ , C ６ F ５ , C ６ H ４ -CF ３ , F, CH ２ , F, CH ２ Cl or C ２ H ４ -Cl, *R ３ = H or CH ３ , *R ４ = H, CH ３ , C ６ H ５ , CF ３ , C ６ F ５ , C ６ H ４ -CF ３ , F, CH ２ , F, CH ２ Cl or C ２ H ４ -Cl The method according to claim 1 or 2, characterized by the above.

4. The thionolactide in formula (I) is the following thionolactide: (i) R ２ and R ４ A thionolactide as defined in claim 1, except for the hydrogen atom, (ii) R ３ and R ４ A thionolactide, wherein the hydrogen atom is as defined in claim 1, and (iii) R １ , R ２ , R ３ or R ４ is a thionolactide in which is a hydrogen atom The method according to claim 1 or 2, characterized in that it is selected from among.

5. The method according to claim 1 or 2, characterized in that the thionolactide of formula (I) is selected from the thionolactides of formulas (I-1) to (I-14) shown in Table 1 below. Table 1

6. R ９ represents a hydrogen atom, R １０ represents a hydrogen atom, R １１ The method according to claim 1 or 2, characterized in that represents a hydrogen atom or an alkyl group.

7. The monomer of formula (II) above is *Formula (II-1) below: 【Chemistry 4】 Vinyl ester type monomers represented by *The following formula (II-2), 【Transformation 5】 In the formula, R １１ represents a hydrogen atom or an alkyl group, and R １２ represents an alkyl group or an optionally substituted aryl group. α-olefin type monomer represented by formula (II-2) *The following formula (III-1): 【Transformation 6】 N-vinyl type monomers represented by *The following formula (II-3) 【Transformation 7】 In the formula, R １１ R represents a hydrogen atom or an alkyl group. １６ represents an alkyl group. Acrylate and alkaliacrylate-type monomers represented by formula (II-3) The method according to claim 1 or 2, characterized in that it is selected from among.

8. The method according to claim 1 or 2, characterized in that the proportion of monomers of formula (I) is selected such that monomers of formula (I) or a plurality of monomers account for a maximum of 50% in number of monomers of formulas (I) and (II).

9. The method according to claim 1 or 2, characterized in that the radical polymerization step by ring-opening of monomers of formulas (I) and (II) is carried out in bulk or in solution in a solvent.

10. The method according to claim 1 or 2, characterized in that the polymerization is carried out in a solvent, and the total amount of monomers of formula (I) and formula (II) is in the range of 30 to 60% by mass relative to the total mass of the reaction medium.

11. The method according to claim 1 or 2, characterized in that the polymerization step is carried out at a temperature in the range of 5 to 150°C.

12. A copolymer, preferably a biodegradable copolymer, wherein the copolymer contains at least a thioester bond, and in the presence of a radical polymerization initiator, (i) The following equation (I), 【Transformation 8】 During the ceremony, -X is an oxygen atom or a sulfur atom, -R １ , R ２ , R ３ and R ４ These are, independently of each other, a hydrogen atom, a halogen atom, an alkyl group, a haloalkyl group, optionally a substituted phenyl group, a cyano group, optionally a substituted alkyl-phenyl group, optionally a substituted haloalkyl-phenyl group, a carboxylic acid group, R ５ CO represents an ester group that is an alkyl group. ２ R ５ , phosphonic acid group, R ６ａ R represents a hydrogen atom or an alkyl group. ６ｂ P(O)(OR) represents an alkyl group phosphonic acid ester group ６ａ ) ( OR ６ｂ ), sulfonic acid group, R ７ SO represents an alkyl group or haloalkyl group. ３ R ７ , and R ８ａ and R ８ｂ The amide group C(O)NR is one in which each element independently represents a hydrogen atom or an alkyl group, or together forms an alkyl group. ８ａ R ８ｂ Represents a base selected from, At least one cyclic monomer selected from the thionolactide of formula (I), and (ii) The following equation (II), 【Chemistry 9】 During the ceremony, -R ９ This represents a hydrogen atom or a fluorine atom, -R １０ This represents a hydrogen atom or a fluorine atom, -R １１ This represents a hydrogen atom, alkyl group, fluorine atom, or chlorine atom. -R １２ is a hydrogen atom, or the following groups: *Alkyl group, *Haloalkyl groups, *Substituted aryl groups in some cases, *Substituted alkyl-aryl groups may be used. *Imidazolyl group, *Alkylimidazolium group, *Carbazoyl group, *The following formula (III), 【Chemistry 10】 In the formula, the asterisk (*) represents the anchor point of the group in formula (III) to the carbon atom of the compound in formula (II), R １３ and R １４ , either identical or different, represents a hydrogen atom, an alkyl group, optionally a substituted alkyl-aryl group, optionally a substituted aryl group, 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, they form a heterocarbon ring containing 4 to 7 carbon atoms (including carbon atoms with oxygen atoms). Based on equation (III), *-OC(O)R １５ It is a base, R １５ -OC(O)R represents an alkyl group, a haloalkyl group, an optionally substituted alkyl-aryl group, or an optionally substituted aryl group. １５ base, *-C(O)OR １６ It is a base, in the formula R １６ -C(O)OR represents an alkyl group, a haloalkyl group, an optionally substituted alkyl-aryl group, or an optionally substituted aryl group. １６ base, *Phosphonic acid group, *Phosphonic acid ester group P(O)(OR) １７ａ ) ( OR １７ｂ ) and in the formula, R １７ａ R represents a hydrogen atom or an alkyl group. １７ｂ P(O)(OR) represents an alkyl group, a phosphonic acid ester group. １７ａ ) ( OR １７ｂ ) *Sulfonic acid group, *Sulfonic acid ester group SO ３ R １８ And in the formula, R １８ SO represents an alkyl group or haloalkyl group, a sulfonic acid ester group. ３ R １８ , and * Amide group C(O)NR １９ａ R １９ｂ And in the formula, R １９ａ and R １９ｂ These are amide groups C(O)NR, which independently represent a hydrogen atom or an alkyl group, or together form an alkyl group. １９ａ R １９ｂ Represents a base selected from, At least one monomer containing ethylene unsaturated monomer selected from monomers of formula (II) A copolymer, preferably a biodegradable copolymer, characterized by being produced by radical polymerization by ring opening.

13. The copolymer according to claim 12, characterized by being produced by polymerization of a thionolactide of the following formula (I-1) with vinyl acetate, styrene, tert-butyl acrylate, methyl methacrylate, or vinyl pivalate.

14. The copolymer according to claim 12 or 13, characterized in that the level of thioester bonds in the skeleton is at least 2% of the total number of bonds in the skeleton.

15. Use of at least one thionolactide having formula (I) as defined in claim 1 or 2 as a precursor monomer in radical polymerization.

16. The following equation (I'), 【Chemistry 11】 During the ceremony, -X, R １ , R ２ , R ３ and R ４ This is as defined in claim 1 or 2, - Exclude thionolactide from the following formulas (I-1) and (I-2): A thionolactide having formula (I') for carrying out the method according to claim 1 or 2. 【change】

17. The thionolactide according to claim 16, selected from the thionolactides of the following formulas (I-3) to (I-13).

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