Process for radical polymerization of thiocarbonyl lactide

Abstract

The present invention relates to a method for preparing a copolymer, preferably a degradable copolymer or a biodegradable copolymer, from a thiocarbonyl lactide. More specifically, the present invention relates to a method for preparing copolymers, preferably degradable copolymers, by free radical ring-opening polymerization, in particular using at least one thiocarbonyl lactide monomer. The invention also relates to copolymers, preferably degradable copolymers, obtained by carrying out this method, to the use of said monomers of the thiocarbonyl lactide type as precursor monomers in free-radical polymerisation, and to specific thiocarbonyl lactide.

Description

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

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

[0003] At present, most synthetic polymers are synthesized by free radical polymerization of vinyl monomers such as ethylene, methyl methacrylate, styrene and vinyl acetate. The advantage of free radical synthesis methods is that they can tolerate a wide range of functionalities, thus enabling the synthesis of a variety of materials. The application of controlled free radical polymerization technology developed at the end of the 20th century also enables the synthesis of polymers and copolymers with complex structures, such as block copolymers, gradient copolymers or star copolymers, and the control of the average molar mass of the polymer and the molar mass distribution.

[0004] One of the main drawbacks of polymers produced by free radical polymerization is that they are difficult to degrade. In fact, the different monomer units are linked together by carbon-carbon (CC) bonds, which are highly resistant to degradation. This can lead to environmental damage and also limits the use of these polymers in the medical field, where it is very important to avoid the accumulation of high molecular weight polymers in the body.

[0005] One method of introducing degradable properties into synthetic polymers obtained by free radical polymerization is to use cyclic comonomers that are polymerized by free radical ring opening polymerization (RROP). These monomers are mainly of two types: vinyl type and exo-methylene type. When the cyclic comonomers of vinyl type or exo-methylene type have degradable functionality, they can be introduced into the polymer backbone to make them degradable copolymers.

[0006] The polymerization of these monomers is carried out by free radical addition to the double bond, followed by ring opening and formation of chain-like species according to the following reaction schemes (1) and (2) involving vinyl monomers and exo-methylene monomers, respectively:

[0007]

[0008] Reaction scheme (1)

[0009]

[0010] Reaction scheme (2)

[0011] Vinyl-type monomers include vinylcyclopropane, which was introduced in the 1960s. Exo-methylene monomers include ketene acetals, which were introduced in the 1980s, and in particular, include 2-methylene-1,3-dione. Alkanes (MDO), which are converted to esters during free radical polymerization [Y=Y'=O in reaction scheme (2)]. Monomeric MDO has been studied in controlled radical polymerization, in particular in Hedir et al., Biomacromolecules, 2015, 16, 2049-2058. In general, ketene acetals copolymerize easily with vinyl esters and vinyl ethers, but are more difficult to copolymerize with styrene monomers, (meth)acrylates and (meth)acrylamides. In addition, they are difficult to synthesize and are usually obtained in rather low yields. Other exo-methylene monomers have also been described, such as cyclic allyl sulfides (such as 2-methyl-7-methylene-1,5-dithiooctane).

[0012] Recently, the use of thiocarbonyl lactide, dibenzo[c,e]oxepane-5-thione (DOT), has been described in free radical polymerization. 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 inert in the presence of methyl methacrylate, delays the free radical polymerization of styrene without being introduced into the polymer backbone, and inhibits the polymerization of vinyl acetate and N-vinyl pyrrolidone. In addition, its synthesis is complicated. Other thiocarbonyl lactones, such as γ-phenyl-γ-butyrolactone and 4-thiocarbonylphthalide, were tested for copolymerization with different monomers and found to be inert [Bingham et al., Chem. Commun., 2019, 55, 55]. Finally, Ivanchenko et al. [Polymer Chemistry, 2021, 12, 1931-1938] describe the use of thiocarbonyl caprolactone, which was found to be inert toward n-butyl acrylate.

[0013] Therefore, there is a need for simple synthetic methods that provide novel synthetic polymers of different structures, preferably degradable polymers, or even biodegradable polymers, preferably with good yields. There is also a need for precursor monomers that can react with comonomers of various structures, for example precursor monomers that react with activated comonomers such as styrene or acrylates, and precursor monomers that react with non-activated comonomers such as vinyl esters.

[0014] Surprisingly, the inventors have developed a process for free radical ring-opening polymerization that is able to achieve these objectives and, in particular, provides a wide range of reactivity.

[0015] Therefore, a first object of the present invention is a process for preparing at least one copolymer, preferably at least one degradable copolymer, comprising at least one step of free radical polymerization by ring opening of at least one cyclic monomer using at least one monomer comprising an ethylenically unsaturated bond, in the presence of a free radical polymerization initiator, said process being characterized in that:

[0016] (i) The cyclic monomer is selected from the thiocarbonyl lactide of the following formula (I):

[0017]

[0018] in:

[0019] -X is an oxygen atom or a sulfur atom;

[0020] -R 1 , R 2 , R 3 and R 4 Each independently represents a hydrogen atom, a halogen atom, a group selected from the following groups: an alkyl radical, a haloalkyl radical, an optionally substituted phenyl radical, a cyano group (CN), an optionally substituted alkyl-phenyl radical, an optionally substituted haloalkyl-phenyl radical, a carboxylic acid radical (COOH), an R having an alkyl radical 5 Ester radical CO2R 5 , phosphonic acid radical (PO(OH)2), R having a hydrogen atom or an alkyl radical 6a and R representing an alkyl radical 6b The phosphonate radical P(O)(OR 6a )(OR 6b ), sulfonic acid radical (SO3H), R having an alkyl radical or a halogenated alkyl radical 7 Sulfonate radical SO3R 7 , and R each independently represents a hydrogen atom or an alkyl radical or together forms an alkyl radical 8a and R 8b The amide radical C(O)NR 8a R 8b ;

[0021] And the characteristics are:

[0022] (ii) The monomer containing an ethylene unsaturated bond is selected from the monomer of the following formula (II):

[0023]

[0024] in:

[0025] -R 9represents a hydrogen atom or a fluorine atom;

[0026] -R 10 represents a hydrogen atom or a fluorine atom;

[0027] -R 11 represents a hydrogen atom, an alkyl radical, a fluorine atom or a chlorine atom;

[0028] -R 12 represents a hydrogen atom, or a group selected from the following groups:

[0029] *Alkyl radicals,

[0030] *Haloalkyl radicals,

[0031] * an optionally substituted aryl radical,

[0032] *optionally substituted alkyl-aryl radicals;

[0033] *Imidazole,

[0034] *Alkyl imidazole base,

[0035] *Carbazolyl,

[0036] * A group of the following formula (III):

[0037]

[0038] The asterisk (*) indicates the binding site of the group of formula (III) to the carbon atom of the compound of formula (II), and the same or different R 13 and R 14 represents a hydrogen atom, an alkyl radical, an optionally substituted alkyl-aryl radical, an optionally substituted aryl radical, a glycidyl group, or R 13 and R 14 The nitrogen atom and the carbon atom of the radical of formula (III) to which it is bonded together form a heterocarbocyclic ring containing 4 to 7 carbon atoms (including the carbon atom carrying the oxygen atom),

[0039] *-OC(O)R 15 Group, where R 15 represents an alkyl radical, a haloalkyl radical, an optionally substituted alkyl-aryl radical, an optionally substituted aryl radical,

[0040] *-C(O)OR 16 Group, where R 16 represents an alkyl radical, a haloalkyl radical, an optionally substituted alkyl-aryl radical or an optionally substituted aryl radical,

[0041] * Phosphonic acid group (PO(OH)2),

[0042] *Phosphonate group P(O)(OR 17a )(OR 17b ), where R 17a represents a hydrogen atom or an alkyl radical, R 17b represents an alkyl radical,

[0043] *Sulfonic acid group (SO3H),

[0044] *Sulfonate group SO3R 18 , where R 18 represents an alkyl radical or a haloalkyl radical, and

[0045] *Amide group C(O)NR 19a R 19b , where R 19a and R 19b Each independently represents a hydrogen atom or an alkyl radical, or together forms an alkyl radical.

[0046] By this process, copolymers can now be obtained in a simple manner, preferably in good yields, which copolymers are preferably degradable copolymers whose degradability can be easily adjusted by varying the respective ratios of the monomers of formula (I) and formula (II).

[0047] In the method of the present invention, the ring opening of the cyclic monomer (I) can form a unit containing a thioester bond in the copolymer, when X is an oxygen atom, it refers to an ester bond. In addition, part of the cyclic monomer (I) can also react with the monomer (II) by free radical polymerization but without ring opening. In addition to the monomer unit (I) having a thioester bond and the ester bond when X is an oxygen atom, the copolymer obtained thereby also contains a cyclic monomer unit (I) having an adjacent dithioester bond and / or a thioacetal bond.

[0048] Therefore, the degradability of the copolymer is provided by the presence of thioester bonds and optional adjacent dithioester bonds and / or thioacetal bonds, which is the result of the monomers of formula (I) being introduced into the copolymer main chain. The larger the ratio of the monomers relative to formula (II), the stronger the degradability of the copolymer. Therefore, the length of the fragment obtained after degradation is inversely proportional to the amount of the monomers of formula (I) introduced into the copolymer main chain. In addition, the chemical groups at the ends of the fragments obtained are functional groups and reactive groups. In addition, the thiocarbonyl lactide monomers of formula (I) used in the free radical copolymerization reaction of the method according to the present invention can be easily synthesized by non-sulfur precursors such as commercially available α-hydroxy acids according to conventional techniques known to those skilled in the art, so as to form lactide by thiocarbonylation, thereby obtaining thiocarbonyl lactide. In addition, monomer (I) has the ability to react with activated monomers and with non-activated monomers, activated monomers such as styrene, its derivatives or acrylates, and non-activated monomers such as vinyl esters. Finally, most of the monomers of formula (II) can be obtained from commercial channels.

[0049] The monomer (I) of the present invention is different from the monomers known in the prior art, such as thiocarbonyl lactide (or dithiocarbonyl lactide) containing -S(C=O)- units. Therefore, dithiocarbonyl lactide does not contain a C=S thiocarbonyl bond. This cyclic di(thioester) can be polymerized by non-radical ring-opening using basic catalysis to produce degradable poly(thioesters). This monomer cannot copolymerize with the comonomer (II) of the present invention by a free radical route.

[0050] According to the invention, a degradable polymer is a polymer whose main chain contains bonds that are easily cleavable, in particular by chemical hydrolysis, by aminolysis or by enzymatic digestion, thereby generating smaller and potentially less polluting molecules. According to the invention, in particular, the bonds are thioester bonds, and optionally ortho-dithioester bonds and / or thioacetal bonds.

[0051] According to the present invention, the term "thiocarbolide monomer of formula (I)" includes the thiocarbolide corresponding to the compound of formula (I), wherein R 1 =H, R 3 =H and R 2 =CH3, R 4 =CH3; and any of the above derivatives of thiocarbonyl lactide corresponding to any compound of formula (I), wherein R 1 , R 2 , R 3 , R 4 As defined in the present invention.

[0052] Thiocarbonyl lactide monomer (I)

[0053] X is an oxygen atom or a sulfur atom, preferably an oxygen atom.

[0054] R 1 , R 2 , R 3 and R 4 Each independently represents a hydrogen atom, a halogen atom, a group selected from the following groups: an alkyl radical, a haloalkyl radical, an optionally substituted phenyl radical, a cyano group (CN), an optionally substituted alkyl-phenyl radical, an optionally substituted haloalkyl-phenyl radical, a carboxylic acid radical (COOH), an R having an alkyl radical 5 Ester radical CO2R 5 , phosphonic acid radical (PO(OH)2), R having a hydrogen atom or an alkyl radical 6a and R representing an alkyl radical 6b The phosphonate radical P(O)(OR 6a )(OR 6b ), sulfonic acid radical (SO3H), R having an alkyl radical or a halogenated alkyl radical 7 Sulfonate radical SO3R 7 , and R each independently represents a hydrogen atom or an alkyl radical or together forms an alkyl radical 8a and R 8b The amide radical C(O)NR 8a R 8b .

[0055] As R 1 , R 2 , R 3 and / or R 4 The halogen atom of the group is preferably a fluorine atom.

[0056] As R 1 , R 2 , R 3 and / or R 4 The alkyl radical of the group can be straight-chain or branched, cyclic or acyclic. The alkyl radical is preferably straight-chain and acyclic. The alkyl radical can contain 1 to 22 carbon atoms, preferably 1 to 6 carbon atoms, particularly preferably 1 to 3 carbon atoms. The alkyl radical is advantageously a methyl or ethyl group.

[0057] In the present invention, the term "haloalkyl" refers to an alkyl radical containing one or more than one halogen atom, and the halogen atom is preferably selected from chlorine atom and fluorine atom.

[0058] As R 1 , R 2 , R 3 and / or R 4The haloalkyl radical of the group can be straight or branched, cyclic or acyclic. The haloalkyl radical is preferably straight and acyclic. The haloalkyl radical can contain 1 to 18 carbon atoms, preferably 1 to 6 carbon atoms, particularly preferably 1 to 3 carbon atoms. The haloalkyl radical is advantageously a trifluoromethyl, fluoromethyl, chloromethyl or chloroethyl group.

[0059] In the present invention, the term "optionally substituted phenyl" refers to 1 , R 2 , R 3 and / or R 4 The phenyl radical of the radical may be substituted by one or more than one substituent, for example a halogen atom, preferably selected from chlorine atoms and fluorine atoms, an alkyl group and a haloalkyl group.

[0060] The haloalkyl group as a substituent of the phenyl radical preferably contains from 1 to 3 carbon atoms. Advantageously, the haloalkyl group is trifluoromethyl.

[0061] The alkyl group as a substituent of the phenyl radical preferably contains from 1 to 3 carbon atoms. Advantageously, the alkyl group is methyl.

[0062] The phenyl radical substituted by one or more than one halogen atom is preferably a pentafluorinated phenyl radical -C6F5.

[0063] As R 1 , R 2 , R 3 and / or R 4 The optionally substituted alkyl-phenyl radical of the group is a radical comprising at least one alkyl radical and at least one optionally substituted phenyl radical directly connected by a covalent (optionally substituted phenyl radical) carbon-(alkyl radical) carbon bond, the optionally substituted phenyl radical and the alkyl radical being as described above for R 1 , R 2 , R 3 and R 4 The alkyl radical is directly linked to the thiocarbonyl lactide via a carbon atom. The optionally substituted alkyl-phenyl radical is advantageously a benzyl radical or a pentafluorobenzyl radical.

[0064] As R 1 , R 2 , R 3 and / or R 4The optionally substituted haloalkyl-phenyl radical of the group is a radical comprising at least one haloalkyl radical and at least one optionally substituted phenyl radical directly connected via a (optionally substituted phenyl radical) carbon-(haloalkyl radical) carbon covalent bond, the optionally substituted phenyl radical and the haloalkyl radical being as described above for R 1 , R 2 , R 3 and R 4 The haloalkyl radical is directly linked to the thiocarbonyl lactide via a carbon atom.

[0065] As R 5 The alkyl radical of the group can be straight-chain or branched, cyclic or acyclic. The alkyl radical is preferably straight-chain and acyclic. The alkyl radical can contain 1 to 22 carbon atoms, preferably 1 to 6 carbon atoms, particularly preferably 1 to 3 carbon atoms. The alkyl radical is advantageously a methyl or ethyl group.

[0066] As R 6a or R 6b The alkyl radical of the group can be straight-chain or branched, cyclic or acyclic. The alkyl radical is preferably straight-chain and acyclic. The alkyl radical can contain 1 to 22 carbon atoms, preferably 1 to 6 carbon atoms, particularly preferably 1 to 3 carbon atoms. The alkyl radical is advantageously a methyl or ethyl group.

[0067] As R 7 The alkyl radical of the group can be straight-chain or branched, cyclic or acyclic. The alkyl radical is preferably straight-chain and acyclic. The alkyl radical can contain 1 to 22 carbon atoms, preferably 1 to 6 carbon atoms, particularly preferably 1 to 3 carbon atoms. The alkyl radical is advantageously a methyl or ethyl group.

[0068] As R 7 The haloalkyl radical of the group can be straight or branched, cyclic or acyclic. The haloalkyl radical is preferably straight and acyclic. The haloalkyl radical can contain 1 to 18 carbon atoms, preferably 1 to 6 carbon atoms, particularly preferably 1 to 3 carbon atoms. The haloalkyl radical is advantageously a trifluoromethyl group.

[0069] As R 8a or R 8b The alkyl radical of the group can be straight-chain or branched, cyclic or acyclic. The alkyl radical is preferably straight-chain and acyclic. The alkyl radical can contain 1 to 22 carbon atoms, preferably 1 to 6 carbon atoms, particularly preferably 1 to 3 carbon atoms. The alkyl radical is advantageously a methyl or ethyl group.

[0070] When R 8a and R 8b When the groups together form an alkyl radical, the obtained 8a and R 8b Together they form a nitrogen ring of an alkyl radical, in particular a nitrogen ring containing 5 carbon atoms (piperidinyl ring).

[0071] Adjusting the R of thiocarbonyl lactide (I) 1 , R 2 , R 3 and R 4 The group can increase its reactivity towards non-activated monomers (II), such as vinyl ester type monomers, or towards activated monomers (II), such as acrylate type monomers, acrylamide type monomers or styrene type monomers.

[0072] R 1 , R 2 , R 3 and R 4 Each independently preferably represents a hydrogen atom, a halogen atom, a group selected from an alkyl radical, a haloalkyl radical, an optionally substituted phenyl radical, an optionally substituted alkyl-phenyl radical and an optionally substituted haloalkyl-phenyl radical, particularly preferably a hydrogen atom, a halogen atom, an alkyl radical, a haloalkyl radical and an optionally substituted phenyl radical.

[0073] According to a preferred embodiment of the present invention:

[0074] *R 1 =H or CH3,

[0075] *R 2 =H, CH3, C6H5, CF3, C6F5, C6H4-CF3, F, CH2F, CH2Cl or C2H4-Cl,

[0076] *R 3 =H or CH3,

[0077] *R 4 =H, CH3, C6H5, CF3, C6F5, C6H4-CF3, F, CH2F, CH2Cl or C2H4-Cl.

[0078] The thiocarbonyl lactide of formula (I) is advantageously selected from the following thiocarbonyl lactides:

[0079] (i) thiocarbonyl lactide, wherein R 2 and R 4 As defined in the present invention, alkyl radicals are particularly preferred, excluding hydrogen atoms.

[0080] (ii) thiocarbonyl lactide, wherein R3 and R 4 As defined in the present invention, alkyl radicals are particularly preferred, excluding hydrogen atoms, and

[0081] (iii) thiocarbonyl lactide, wherein R 1 , R 2 , R 3 or R 4 A hydrogen atom.

[0082] In thiocarbonyl lactide (i), R 1 and R 3 Preferred is a hydrogen atom.

[0083] In thiocarbonyl lactide (ii), R 1 and R 2 Preferred is a hydrogen atom.

[0084] Thiocarbonyl lactide (i) and thiocarbonyl lactide (ii) promote copolymerization with the activated monomer (II).

[0085] Thiocarbonyl lactide (iii) promotes copolymerization with the non-activated monomer (II).

[0086] According to a particular embodiment of the present invention, all R 1 and R 2 Group and all R 3 and R 4 This results in a "symmetrical" thiocarbolide (I) which is easier to prepare.

[0087] The thiocarbonyl lactide of formula (I) is advantageously selected from the thiocarbonyl lactides of formula (I-1) to formula (I-13) shown in Table 1 below:

[0088]

[0089] Table 1

[0090] Among the thiocarbolides of formula (I-1) to formula (I-14), the thiocarbolides of formula (I-1), formula (I-13) and formula (I-14) are particularly preferred.

[0091] Monomer (II)

[0092] R 9 Preferably it represents a hydrogen atom.

[0093] R 10 Preferably it represents a hydrogen atom.

[0094] R 11 Preferably it represents a hydrogen atom or an alkyl radical.

[0095] As R11 The alkyl radical of the group can be straight-chain or branched, cyclic or acyclic. The alkyl radical is preferably straight-chain and acyclic. The alkyl radical can contain 1 to 5 carbon atoms, preferably 1 to 3 carbon atoms. The alkyl radical is advantageously a methyl group.

[0096] As R 12 The alkyl radical of the group can be straight-chain or branched, cyclic or acyclic. The alkyl radical is preferably straight-chain and acyclic. The alkyl radical can contain 1 to 22 carbon atoms, preferably 1 to 10 carbon atoms, particularly preferably 1 to 5 carbon atoms, and the alkyl radical is optionally substituted by a hydroxyl radical.

[0097] As R 12 As examples of alkyl radicals of the radical, the following may be mentioned: methyl radical, ethyl radical, isopropyl radical, n-butyl radical, 2-butyl radical, isobutyl radical, tert-butyl radical, n-pentyl radical, isopentyl radical, neopentyl radical, tert-pentyl radical, 2-methylbutyl radical, hexyl radical, n-octyl radical, isooctyl radical, 2-ethyl-1-hexyl radical, 2,2,4-trimethylpentyl radical, nonyl radical, neodecyl radical, decyl radical, dodecyl radical, octadecyl radical, docosyl radical or cyclohexylmethyl radical, preferably a methyl radical or a hexyl radical.

[0098] As R 12 The haloalkyl radical of the group can be straight or branched, cyclic or acyclic. The haloalkyl radical is preferably straight and acyclic. The haloalkyl radical can contain 1 to 22 carbon atoms, preferably 1 to 5 carbon atoms.

[0099] As R 12 The aryl radical of the group may be a monocyclic aromatic hydrocarbon radical or a polycyclic aromatic hydrocarbon radical, optionally substituted with an alkyl radical containing 1 to 5 carbon atoms or an alkoxy radical containing 1 to 5 carbon atoms.

[0100] As R 12 As examples of the aryl radical of the radical, there may be mentioned in particular a phenyl radical, a trityl radical, a naphthyl radical, an anthracenyl radical and a pyrenyl radical. Among these radicals, the phenyl radical is particularly preferred.

[0101] As R 12An optionally substituted alkyl-aryl radical of a group is a radical comprising at least one alkyl radical and at least one optionally substituted aryl radical directly connected by a covalent (optionally substituted aryl radical) carbon-(alkyl radical) carbon bond, the optionally substituted aryl radical and the alkyl radical being as described above for R 12 The alkyl radical is directly linked to the vinyl function (double bond) of monomer (II) via a carbon atom. The optionally substituted alkyl-aryl radical is advantageously a benzyl radical, a p-methoxybenzyl radical or a pentafluorobenzyl radical.

[0102] As R 12 Alkyl imidazole The alkyl substituents of the free radical preferably contain 1 to 16 carbon atoms, particularly preferably 1 to 5 carbon atoms. 12 Alkyl imidazole The free radical preferably comprises a radical selected from Br - 、BF4 - and PF6 - of the counter ion.

[0103] The group of formula (III)

[0104] As R 13 and / or R 14 The alkyl radical of the group can be straight-chain or branched, cyclic or acyclic. The alkyl radical is preferably straight-chain. The alkyl radical can contain 1 to 22 carbon atoms, preferably 1 to 5 carbon atoms.

[0105] As R 13 and / or R 14 As examples of alkyl radicals of the radical, the following may be mentioned: methyl radical, ethyl radical, isopropyl radical, n-butyl radical, 2-butyl radical, isobutyl radical, tert-butyl radical, n-pentyl radical, isopentyl radical, neopentyl radical, tert-pentyl radical, 2-methylbutyl radical, hexyl radical, n-octyl radical, isooctyl radical, 2-ethyl-1-hexyl radical, 2,2,4-trimethylpentyl radical, nonyl radical, neodecyl radical, decyl radical, dodecyl radical, octadecyl radical, docosyl radical, cyclohexylmethyl radical, adamantyl radical and cyclohexyl radical.

[0106] As R 13 and / or R 14 The aryl radical of the group may be a monocyclic aromatic hydrocarbon radical or a polycyclic aromatic hydrocarbon radical, optionally substituted with an alkyl radical containing 1 to 5 carbon atoms or an alkoxy radical containing 1 to 5 carbon atoms.

[0107] As R 13 and / or R 14 As examples of the aryl radical of the radical, there may be mentioned in particular a phenyl radical, a trityl radical, a naphthyl radical, an anthracenyl radical and a pyrenyl radical. Among these radicals, the phenyl radical is particularly preferred.

[0108] As R 13 and / or R 14 An optionally substituted alkyl-aryl radical of a group is a radical comprising at least one alkyl radical and at least one optionally substituted aryl radical directly connected by a covalent (optionally substituted aryl radical) carbon-(alkyl radical) carbon bond, the optionally substituted aryl radical and the alkyl radical being as described above for R 13 and R 14 The alkyl radical is directly connected to R of formula (III) through a carbon atom. 13 The nitrogen atom of formula (III) is connected to R 14 The optionally substituted alkyl-aryl radical is advantageously a benzyl or pentafluorobenzyl radical.

[0109] When R 13 and R 14 When the nitrogen atom and the carbon atom of the group of formula (III) to which it is bonded form a heterocarbocyclic ring together, it may be, in particular, a pyrrolidone ring, a piperidone ring or a caprolactam ring.

[0110] According to a preferred embodiment of the present invention, the same or different R 13 and R 14 represents a hydrogen atom or an alkyl radical, or R 13 and R 14 The nitrogen atom and the carbon atom of the radical of formula (III) to which it is bonded together form a heterocarbocyclic ring comprising 4 to 7 carbon atoms (including the carbon atom carrying the oxygen atom).

[0111] According to a particularly preferred embodiment, R 13 and R 14 are the same and represent a methyl radical, or, together with the nitrogen atom and the carbon atom of the group of formula (III) to which it is bonded, form a pyrrolidone ring or a caprolactam ring.

[0112] -OC(O)R 15 Group

[0113] As R 15 The alkyl radical of the group can be straight-chain or branched, cyclic or acyclic. The alkyl radical is preferably straight-chain and acyclic. The alkyl radical can contain 1 to 22 carbon atoms, preferably 1 to 5 carbon atoms.

[0114] As R 15 As examples of alkyl radicals of the radical, the following may be mentioned: methyl radical, ethyl radical, isopropyl radical, n-butyl radical, 2-butyl radical, isobutyl radical, tert-butyl radical, n-pentyl radical, isopentyl radical, neopentyl radical, tert-pentyl radical, 2-methylbutyl radical, hexyl radical, n-octyl radical, isooctyl radical, 2-ethyl-1-hexyl radical, 2,2,4-trimethylpentyl radical, nonyl radical, neodecyl radical, decyl radical, dodecyl radical, octadecyl radical, docosyl radical, cyclohexylmethyl radical, adamantyl radical and cyclohexyl radical.

[0115] As R 15 The aryl radical of the group may be a monocyclic aromatic hydrocarbon radical or a polycyclic aromatic hydrocarbon radical, optionally substituted with an alkyl radical containing 1 to 5 carbon atoms or an alkoxy radical containing 1 to 5 carbon atoms.

[0116] As R 15 As examples of the aryl radical of the radical, there may be mentioned in particular a phenyl radical, a trityl radical, a naphthyl radical, an anthracenyl radical and a pyrenyl radical. Among these radicals, the phenyl radical is particularly preferred.

[0117] As R 15 An optionally substituted alkyl-aryl radical of a group is a radical comprising at least one alkyl radical and at least one optionally substituted aryl radical directly connected by a covalent (optionally substituted aryl radical) carbon-(alkyl radical) carbon bond, the optionally substituted aryl radical and the alkyl radical being as described above for R 15 The alkyl radical is directly connected to the carbon atom of the ester functional group via a carbon atom. The optionally substituted alkyl-aryl radical is advantageously a benzyl radical or a pentafluorobenzyl radical.

[0118] As R 15 The haloalkyl radical of the group can be straight or branched, cyclic or acyclic. The haloalkyl radical is preferably straight and acyclic. The haloalkyl radical can contain 1 to 22 carbon atoms, preferably 1 to 5 carbon atoms.

[0119] R 15 Preferably it represents an alkyl radical or a haloalkyl radical, particularly preferably an alkyl radical such as a methyl radical or a tert-butyl radical.

[0120] -C(O)OR 16 Group

[0121] As R 16The alkyl radical of the group can be straight-chain or branched, cyclic or acyclic. The alkyl radical is preferably straight-chain and acyclic. The alkyl radical can contain 1 to 22 carbon atoms, preferably 1 to 5 carbon atoms.

[0122] As R 16 As examples of alkyl radicals of the radical, the following may be mentioned: methyl radical, ethyl radical, isopropyl radical, n-butyl radical, 2-butyl radical, isobutyl radical, tert-butyl radical, n-pentyl radical, isopentyl radical, neopentyl radical, tert-pentyl radical, 2-methylbutyl radical, hexyl radical, n-octyl radical, isooctyl radical, 2-ethyl-1-hexyl radical, 2,2,4-trimethylpentyl radical, nonyl radical, neodecyl radical, decyl radical, dodecyl radical, octadecyl radical, behenyl radical, isobornyl radical, cyclohexylmethyl radical, adamantyl radical and cyclohexyl radical.

[0123] As R 16 The aryl radical of the group may be a monocyclic aromatic hydrocarbon radical or a polycyclic aromatic hydrocarbon radical, optionally substituted with an alkyl radical containing 1 to 5 carbon atoms or an alkoxy radical containing 1 to 5 carbon atoms.

[0124] As R 16 As examples of the aryl radical of the radical, there may be mentioned in particular a phenyl radical, a trityl radical, a naphthyl radical, an anthracenyl radical and a pyrenyl radical. Among these radicals, the phenyl radical is particularly preferred.

[0125] As R 16 An optionally substituted alkyl-aryl radical of a group is a radical comprising at least one alkyl radical and at least one optionally substituted aryl radical directly connected by a covalent (optionally substituted aryl radical) carbon-(alkyl radical) carbon bond, the optionally substituted aryl radical and the alkyl radical being as described above for R 16 The alkyl radical is directly connected to the carbon atom of the ester functional group via a carbon atom. The optionally substituted alkyl-aryl radical is advantageously a benzyl radical or a pentafluorobenzyl radical.

[0126] As R 16 The haloalkyl radical of the group can be straight or branched, cyclic or acyclic. The haloalkyl radical is preferably straight and acyclic. The haloalkyl radical can contain 1 to 22 carbon atoms, preferably 1 to 5 carbon atoms.

[0127] R 16 Preferably it denotes an alkyl radical, in particular a methyl radical or a tert-butyl radical.

[0128] As R 17a or R 17b The alkyl radical of the group can be straight-chain or branched, cyclic or acyclic. The alkyl radical is preferably straight-chain and acyclic. The alkyl radical can contain 1 to 22 carbon atoms, preferably 1 to 6 carbon atoms, particularly preferably 1 to 3 carbon atoms. The alkyl radical is advantageously a methyl or ethyl group.

[0129] As R 18 The alkyl radical of the group can be straight-chain or branched, cyclic or acyclic. The alkyl radical is preferably straight-chain and acyclic. The alkyl radical can contain 1 to 22 carbon atoms, preferably 1 to 6 carbon atoms, particularly preferably 1 to 3 carbon atoms. The alkyl radical is advantageously a methyl or ethyl group.

[0130] As R 18 The haloalkyl radical of the group can be straight or branched, cyclic or acyclic. The haloalkyl radical is preferably straight and acyclic. The haloalkyl radical can contain 1 to 18 carbon atoms, preferably 1 to 6 carbon atoms, particularly preferably 1 to 3 carbon atoms. The haloalkyl radical is advantageously a trifluoromethyl group.

[0131] As R 19a or R 19b The alkyl radical of the group can be straight-chain or branched, cyclic or acyclic. The alkyl radical is preferably straight-chain and acyclic. The alkyl radical can contain 1 to 22 carbon atoms, preferably 1 to 6 carbon atoms, particularly preferably 1 to 3 carbon atoms. The alkyl radical is advantageously a methyl or ethyl group.

[0132] When R 19a and R 19b When the groups together form an alkyl radical, the obtained 19a and R 19b Together they form a nitrogen ring of an alkyl radical, in particular a nitrogen ring containing 5 carbon atoms (piperidinyl ring).

[0133] According to a preferred embodiment, the monomer of formula (II) is selected from:

[0134] * Vinyl ester monomer represented by the following formula (II-1):

[0135]

[0136] Where R 15 As defined in the present invention,

[0137] *α-olefin monomer represented by the following formula (II-2):

[0138]

[0139] Where R 11 represents a hydrogen atom or an alkyl radical as defined in the present invention, R 12 represents an alkyl radical or an optionally substituted aryl radical as defined in the present invention,

[0140] *N-vinyl type monomer represented by the following formula (III-1):

[0141]

[0142] Its R 13 and R 14 As defined in the present invention,

[0143] *Acrylate monomer and alkylacrylate monomer represented by the following formula (II-3):

[0144]

[0145] Where R 11 represents a hydrogen atom or an alkyl radical as defined in the present invention, R 16 It represents an alkyl radical as defined in the present invention.

[0146] Among the monomers of formula (II-1), mention may be made of vinyl acetate, vinyl pivalate, vinyl trifluoroacetate, vinyl chloroacetate, vinyl propionate, vinyl butyrate, vinyl neodecanoate (R 15 =C9H 19 Among the monomers of formula (II-1), vinyl acetate and vinyl pivalate are particularly preferred.

[0147] The monomer of formula (II-2) includes ethylene and octene, and ethylene is particularly preferred.

[0148] Among the monomers of formula (III-1), mention may be made in particular of acyclic N-vinyl monomers, such as N-vinylformamide, N-vinylacetamide and N-methyl-N-vinylacetamide, and cyclic N-vinyl monomers (when R 13 and R 14 When the nitrogen atom and the carbon atom of the group of formula (III-1) to which it is bonded together form a heterocarbocyclic ring), for example, N-vinylpyrrolidone, N-vinylpiperidone and N-vinylcaprolactam. Among these monomers of formula (III-1), N-vinylacetamide and N-vinylpyrrolidone are particularly preferred.

[0149] Among the monomers of formula (II-3), mention may in particular be made of methyl acrylate, n-butyl acrylate, tert-butyl acrylate, 2-ethylhexyl acrylate, methyl methacrylate, tert-butyl methacrylate, isobornyl methacrylate or adamantyl methacrylate.

[0150] According to the method of the present invention, the ratio of monomers of formula (I) is preferably selected so that the amount of one or more monomers of formula (I) is at most 50% relative to the total amount of monomers of formula (I) and formula (II). According to a particularly preferred embodiment, the amount of one or more monomers of formula (I) is about 5% to 30%, even more preferably about 10% to 20%, relative to the total amount of monomers of formula (I) and formula (II). In fact, when the ratio of the amount of monomers of formula (I) is less than 5%, the degradability of the polymer is not high, which is unattractive compared to non-degradable polymers. When the ratio of the amount of monomers of formula (I) is greater than 30%, the free radical polymerization method by ring opening will be weakened, in particular slowed down.

[0151] For the purposes of the present invention, a free radical polymerization initiator means a chemical species capable of forming free radicals, ie free radicals having one or more than one unpaired electron in their outer shell.

[0152] According to the process of the invention, the free-radical polymerization initiator is preferably selected from organic peroxides and organic hydroperoxides, azo derivatives and free-radical generating redox couples (redox systems).

[0153] Among the organic peroxides and organic hydroperoxides, mention may be made in particular of dilauroyl peroxide (LPO), tert-butyl peroxyacetate, tert-butyl peroxybenzoate, tert-butyl peroxyoctanoate, tert-butyl peroxydodecanoate, tert-butyl peroxyisobutyrate, tert-amyl peroxypivalate, tert-butyl peroxypivalate, diisopropyl peroxydicarbonate, dicyclohexyl peroxydicarbonate, diisopropyl peroxide, dibenzoyl peroxide, potassium peroxydisulfate, sodium peroxydisulfate, ammonium peroxydisulfate, cumene hydroperoxide and tert-butyl hydroperoxide. Among these organic peroxides, LPO and tert-butyl hydroperoxide are particularly preferred.

[0154] Among the azo derivatives, mention may be made in particular of 2,2'-azobis(isobutyronitrile) or AIBN, 2,2'-azobis(2-cyano-2-butane), 2,2'-azobisdimethylisobutyrate, 4,4'-azobis-(4-cyanovaleric acid), 1,1'-azobis(cyclohexanecarbonitrile), 2-(tert-butylazo)-2-cyanopropane, 2,2'-azobis-[2-methyl-N(1,1)-bis(hydroxymethyl)-2-hydroxyethyl]propionamide, 2,2'-azobis-[2-methyl-N-hydroxyethyl]propionamide, 2,2'-azobis-(N,N'-dimethyleneisobutyramidine) dihydrochloride, 2,2'-azobis-(2-amidinopropane) dihydrochloride Salts, 2,2'-azobis-(N,N'-dimethyleneisobutylamine), 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-(isobutyramide) dihydrate, 2,2'-azobis-(2,2,4-trimethylpentane) and 2,2'-azobis-(2-methylpropane). Among these azo derivatives, 2,2'-azobis(isobutyronitrile) and 1,1'-azobis-(cyclohexanecarbonitrile) are particularly preferred.

[0155] For example, the redox system is selected from the system comprising the following combinations, for example:

[0156] - mixtures of hydrogen peroxide, dialkyl peroxides, hydroperoxides, peroxyesters, percarbonates and similar compounds with iron salts, titanium salts, zinc formaldehyde sulfoxylate or sodium formaldehyde sulfoxylate and reducing sugars,

[0157] - mixtures of alkali metal or ammonium persulfates, perborates or perchlorates with alkali metal bisulfites, such as sodium metabisulfite, and reducing sugars, and

[0158] - A mixture of an alkali metal persulfate with an aromatic phosphonic acid, such as phenylphosphonic acid, and a reducing sugar.

[0159] Among these redox systems, the combination of ammonium persulfate and sodium formaldehyde sulfoxylate and the combination of tert-butyl hydroperoxide and ascorbic acid are particularly preferred.

[0160] Photochemical initiators can also be used under ultraviolet (UV) or visible light. Examples of UV initiators include 2,2-dimethoxy-2-phenylacetophenone, benzophenone / amine pairs or benzophenone / alcohol pairs. Thioxanthone can be used as a visible light initiator. Finally, some xanthate-type or trithiocarbonate-type RAFT control agents can also be used, which are also excellent photochemical initiators in the UV and visible range.

[0161] According to the method of the present invention, the amount of the free radical polymerization initiator used is generally determined so that the amount of free radicals generated is at most about 5 mol %, preferably at most about 1 mol %, relative to the total amount of monomers of formula (I) and formula (II).

[0162] The step of free radical polymerization by ring opening of monomers of formula (I) and formula (II) can be carried out in bulk (solvent-free) or in solution in a solvent, in particular a solvent being selected which enables the reaction medium to remain uniform throughout the polymerization reaction. Usually, the solvent is organic, but if the solubility of the monomer permits, aqueous solvents such as water or a mixture of water and a cosolvent may also be used. The polymerization of monomers of formula (I) and formula (II) may also be carried out in a heterogeneous medium, the polymer formed being insoluble in the reaction medium. The polymerization may also be carried out by precipitation, or in a dispersion, emulsion or suspension.

[0163] According to a preferred embodiment of the present invention, water, a water-alcohol mixture or an organic solvent is used as the reaction medium. An organic solvent is preferred.

[0164] When polymerization is carried out in bulk, i.e. without solvent, the total amount of polymerizable substances in the reaction medium (the total amount of monomers of formula (I) and formula (II)) can be 100%. When polymerization is carried out in a solvent, the total amount is about 10% to 90% by mass, preferably about 20% to 80% by mass, and more preferably about 30% to 60% by mass, relative to the gross mass of the reaction medium.

[0165] The polymerization step of the process according to the invention can be carried out at a temperature of about 5° C. to 150° C., depending on the nature of the monomers of formula (I) and formula (II) used in the reaction process. According to a preferred embodiment of the process according to the invention, the polymerization step is carried out at a temperature of about 20° C. to 130° C., even more preferably about 40° C. to 110° C.

[0166] The duration of the polymerization step is generally between about 1 hour and 12 hours, even more preferably between about 2 hours and 8 hours.

[0167] As mentioned above, the polymerization step is preferably carried out only in the presence of monomers of formula (I) and formula (II) and a free radical polymerization initiator, i.e. without using a polymerization control agent. However, according to an alternative to the method of the present invention, the polymerization step can also be carried out in the presence of a polymerization control agent, thereby obtaining a copolymer, preferably a degradable copolymer, a block copolymer, a composition gradient copolymer, a comb copolymer, a star graft copolymer or even a hyperbranched copolymer. In fact, different controlled radical polymerization methods are known, so that structurally controlled and quality-controlled polymers can be obtained. These methods are defined according to the chemical nature of the control agent involved. The present invention can relate to a control agent for a controlled radical polymerization technique using reversible addition-fragmentation chain transfer (RAFT), in particular in the presence of xanthates (macromolecules designed by xanthate exchange (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 complexation-mediated polymerization (RCMP). These various techniques are described in Polymer Chemistry 2018, 9, 4947-4967 and references cited therein.

[0168] Thus, the process of the present invention produces copolymers having at least thioester bonds, which copolymers are susceptible to degradation.

[0169] In the method, a cyclic monomer (I) and at least one monomer (II) containing an ethylene unsaturated bond are used in the presence of a free radical polymerization initiator, and part of the cyclic monomer (I) can also be consumed in the polymerization process without ring opening. The copolymer thus obtained contains, in addition to the ring-opened thioester bond, cyclic monomer (I) units having adjacent dithioester bonds and / or thioacetal bonds. These cyclic monomer units (I) having adjacent dithioester bonds and / or thioacetal bonds have the advantage of being sensitive to chemical attack and are therefore potentially degradable.

[0170] The degradable copolymers obtained by implementing the process according to the invention are novel per se and therefore constitute a second object of the present invention.

[0171] Therefore, a second object of the present invention is also a copolymer, preferably a degradable copolymer, characterized in that it contains at least a thioester bond and characterized in that it is produced by free radical polymerization by ring opening of the following monomers in the presence of a free radical polymerization initiator:

[0172] (i) at least one cyclic monomer selected from the group consisting of thiocarbonyl lactide of formula (I):

[0173]

[0174] in:

[0175] -X is an oxygen atom or a sulfur atom;

[0176] -R 1 , R 2 , R 3 and R 4 Each independently represents a hydrogen atom, a halogen atom, a group selected from the following groups: an alkyl radical, a haloalkyl radical, an optionally substituted phenyl radical, a cyano group (CN), an optionally substituted alkyl-phenyl radical, an optionally substituted haloalkyl-phenyl radical, a carboxylic acid radical (COOH), an R having an alkyl radical 5 Ester radical CO2R 5 , phosphonic acid radical (PO(OH)2), R having a hydrogen atom or an alkyl radical 6a and R representing an alkyl radical 6b The phosphonate radical P(O)(OR 6a )(OR 6b ), sulfonic acid radical (SO3H), R having an alkyl radical or a halogenated alkyl radical 7 Sulfonate radical SO3R 7 , and R each independently represents a hydrogen atom or an alkyl radical or together forms an alkyl radical 8a and R 8b The amide radical C(O)NR 8a R 8b ;and

[0177] (ii) at least one monomer containing an ethylenically unsaturated bond selected from monomers of the following formula (II):

[0178]

[0179] in:

[0180] -R 9 represents a hydrogen atom or a fluorine atom;

[0181] -R 10 represents a hydrogen atom or a fluorine atom;

[0182] -R 11 represents a hydrogen atom, an alkyl radical, a fluorine atom or a chlorine atom;

[0183] -R 12 represents a hydrogen atom, or a group selected from the following groups:

[0184] *Alkyl radicals,

[0185] *Haloalkyl radicals,

[0186] * an optionally substituted aryl radical,

[0187] *optionally substituted alkyl-aryl radicals;

[0188] *Imidazole,

[0189] *Alkyl imidazole base,

[0190] *Carbazolyl,

[0191] * A group of the following formula (III):

[0192]

[0193] The asterisk (*) indicates the binding site of the group of formula (III) to the carbon atom of the compound of formula (II), and the same or different R 13 and R 14 represents a hydrogen atom, an alkyl radical, an optionally substituted alkyl-aryl radical, an optionally substituted aryl radical, a glycidyl group, or R 13 and R 14 The nitrogen atom and the carbon atom of the radical of formula (III) to which it is bonded together form a heterocarbocyclic ring containing 4 to 7 carbon atoms (including the carbon atom carrying the oxygen atom),

[0194] *-OC(O)R 15 Group, where R 15 represents an alkyl radical, a haloalkyl radical, an optionally substituted alkyl-aryl radical, an optionally substituted aryl radical,

[0195] *-C(O)OR 16 Group, where R 16 represents an alkyl radical, a haloalkyl radical, an optionally substituted alkyl-aryl radical or an optionally substituted aryl radical,

[0196] * Phosphonic acid group (PO(OH)2),

[0197] *Phosphonate group P(O)(OR 17a )(OR 17b ), where R 17a represents a hydrogen atom or an alkyl radical, R 17b represents an alkyl radical,

[0198] *Sulfonic acid group (SO3H),

[0199] *Sulfonate group SO3R 18 , where R 18 represents an alkyl radical or a haloalkyl radical, and

[0200] *Amide group C(O)NR 19a R 19b , where R 19a and R 19b Each independently represents a hydrogen atom or an alkyl radical, or together forms an alkyl radical.

[0201] The preferences stated above with respect to the monomers of formula (I) and formula (II) in relation to the first object of the present invention also apply to the second object of the present invention.

[0202] According to a particular and preferred embodiment of the invention, the copolymer is produced by the polymerization of thiocarbonyl lactide (I-1) with vinyl acetate, styrene, tert-butyl acrylate, methyl methacrylate or vinyl pivalate.

[0203] According to a preferred embodiment of the second aspect of the present invention, the copolymer, preferably the degradable copolymer, is a random copolymer.

[0204] The copolymers according to the invention, preferably degradable copolymers, preferably have a number average molar mass of about 2000 to 200000 g / mol, even more preferably about 5000 to 100000 g / mol.

[0205] The polymer, preferably the degradable polymer, according to the present invention preferably has a polydispersity index of 1.2 to 4, more preferably 1.4 to 3.

[0206] The degradable copolymer according to the present invention preferably has a level of thioester bonds in its main chain of at least 2% by number, preferably 2% to 20% by number, more preferably 5% to 15% by number, relative to the total number of bonds in its main chain.

[0207] The copolymers can also contain ortho-dithioester bonds and / or thioacetal bonds which are also degradable.

[0208] According to the invention, the backbone of the copolymer refers to the longest bond connection, ie the bonds excluding the side substituents.

[0209] Due to its degradable nature, the copolymers according to the invention can be used in all types of industry. By way of example, mention may be made in particular of the biopharmaceutical field, agriculture, cosmetics, oil extraction, detergents, salting out and packaging of active products.

[0210] If the copolymers of the present invention exhibit little or no degradability, they may also be used in the medical field, particularly in the field of dental fillings, or any type of field where it is desirable to reduce polymerization shrinkage.

[0211] Furthermore, a third object of the present invention is the use of at least one thiocarbolide having the formula (I) as defined in the first object of the present invention as a precursor monomer for free radical polymerization.

[0212] Free radical polymerisation is as defined in the first object of the present invention.

[0213] Some of the thiocarbolides of formula (I) are novel per se and constitute a fourth object of the present invention.

[0214] Therefore, a fourth object of the present invention is a thiocarbolide for use in implementing the method defined in the first object of the present invention, said thiocarbolide having the following formula (I'):

[0215]

[0216] in:

[0217] -X, R 1 , R 2 , R 3 and R 4 As defined in the first object of the present invention,

[0218] -Except for thiocarbonyl lactide (I-1) and thiocarbonyl lactide (I-2) defined in the present invention.

[0219] Preferably, the thiocarbolide of formula (I') is selected from the thiocarbolides of formula (I-3) to formula (I-14) described in the present invention.

[0220] The lactide precursor of the thiocarbolide of formula (I) or formula (I') described in the present invention can be obtained by dimerization of the corresponding α-hydroxy acid, or in the case of compound (I-13) and compound (I-14), it is obtained by reacting α-hydroxyisobutyric acid with chloroacetyl chloride or chloropropyl chloride. 10 In the presence of HMDSO and hexamethyldisiloxane, the monothiocarbonylation or dithiocarbonylation of lactide can be carried out. BRIEF DESCRIPTION OF THE DRAWINGS

[0221] The present invention is illustrated in the accompanying drawings:

[0222] Figure 1 The chemical degradation of polymer CP2 according to the invention is shown.

[0223] Figure 2 The chemical degradation of polymer CP6 according to the invention is shown.

[0224] Figure 3 The crystal structure of compound (I-13) used in the method according to the present invention is shown.

[0225] Figure 4 The chemical degradation of polymer CP8 according to the invention is shown.

[0226] Figure 5 The crystal structure of compound (I-14) used in the method according to the present invention is shown.

[0227] Figure 6 The chemical degradation of polymer CP10 according to the invention is shown.

[0228] Further features and advantages of the present invention will become apparent from the description of the embodiments set forth hereinafter, to which, however, the present invention is not limited. Example

[0229] Size exclusion chromatography was performed using an apparatus equipped with two Shodex columns (KF-805+KF-804+KF-802.5), a refractive index detector and a light scattering detector, and the analysis was performed in tetrahydrofuran (THF) at 35°C and a flow rate of 1 mL / min.

[0230] Example 1: Synthesis of a degradable thiocarbolide based on styrene and formula (I-1) according to the method of the present invention Copolymer CP1 .

[0231] 1.1 Step 1: Synthesis of thiocarbonyl lactide of formula (I-1)

[0232] P4S 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 double-necked flask with an overhead condenser. The resulting mixture was heated under reflux for 48 hours. The reaction medium was then cooled to room temperature, filtered through a layer of silica gel (50 g), and washed with dichloromethane (DCM). The filtrate was evaporated under reduced pressure and purified by column chromatography (8 / 2 cyclohexane / ethyl acetate eluent). Recrystallization was performed four times to obtain thiocarbonyl lactide crystals (1.8 g) in a yield of 33%. Before use in polymerization, the mixture was heated at 60° C. and 10 -2 The resulting crystals were sublimed under a pressure of mbar.

[0233] 1 H NMR (CDCl3, 300MHz) δ (ppm): 5,06 (q, 1H), 4,98 (q, 1H), 1,79 (d, 3H), 1,76 (d, 3H).

[0234] 13 C NMR (CDCl3, 126MHz) δ (ppm): 211, 4, 167, 5, 78, 4, 75, 1, 19, 3, 15, 5.

[0235] 1.2 Step 2: Synthesis of poly(styrene-co-thiocarbonyl lactide) copolymer CP1

[0236] 6 mg (0.025 mmol) of azobis(cyanocyclohexane) (VAZO-88), 0.08 g (0.5 mmol) of the thiocarbonyl lactide (I-1) obtained in the previous step, 0.468 g (4.5 mmol) of styrene and 10 mg of naphthalene as an internal standard are mixed to form a solution. The thiocarbonyl lactide (monomer of formula (I-1)) accounts for 10% (by mole) relative to styrene (monomer of formula (II)). The solution is transferred to a Carius tube and sealed under vacuum after three degassing cycles. The tube is then placed in an oil bath at 100°C for 5 hours. The polymerization is stopped by rapid cooling. After opening the tube, part of the solution is transferred to an NMR tube to measure the conversion rate of the thiocarbonyl lactide (I-1) after 5 hours of reaction.

[0237] H NMR ( 1 H NMR) is used to measure the transformation efficiency of monomer. For this reason, the signal integral of naphthalene at 7.8ppm as internal standard corresponds to 1, and the signal of 5.10ppm to 4.95ppm is compared, and the two hydrogen atoms of thiocarbonyl lactide (I-1) of this signal correspondence, and the integration result equaling 0 hour with the reaction time is compared. Therefore, the transformation efficiency of thiocarbonyl lactide (I-1) after reaction X hours can be determined according to the following formula 1:

[0238]

[0239] By hydrogen nuclear magnetic resonance spectroscopy ( 1 H NMR) showed that the conversion of the thiocarbonyl lactide (I-1) monomer was 58%, and the conversion of the styrene monomer was 82%. The residual monomers were evaporated, and the number average molar mass (Mn) and polydispersity index (Mw / Mn) of the copolymer CP1 were determined by size exclusion chromatography (eluent: tetrahydrofuran THF) based on the calibration curve of PMMA: Mn = 13200 g / mol; Mw / Mn = 2.3.

[0240] Example 2: Synthesis of a thiocarbonyl lactide based on tert-butyl acrylate and formula (I-1) according to the method of the present invention Degradable copolymer CP2

[0241] 5.3 mg (0.022 mmol) of azobis(cyanocyclohexane) (VAZO-88), 0.07 g (0.44 mmol) of thiocarbonyl lactide (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. The thiocarbonyl lactide (monomer of formula (I-1)) accounted for 10% (by mole) relative to tert-butyl acrylate (monomer of formula (II)). The solution was transferred to a Carlos tube and sealed under vacuum after three degassing cycles. The tube was then placed in an oil bath at 100°C for 5 hours. The polymerization was stopped by rapid cooling. After opening the tube, part of the solution was transferred to an NMR tube to measure the conversion rate of the thiocarbonyl lactide (I-1) after 5 hours of reaction.

[0242] As described in Example 1, by H NMR spectroscopy ( 1 H NMR) showed that the conversion of the thiocarbolide (I-1) monomer was 34%, and the conversion of the tert-butyl acrylate monomer was 33%. The residual monomers were evaporated, and the number average molar mass (Mn) and polydispersity index (Mw / Mn) of the poly(tert-butyl acrylate-co-thiocarbolide) copolymer CP2 were determined by size exclusion chromatography (eluent: THF) based on the calibration curve of PMMA: Mn=8000 g / mol; Mw / Mn=1.7.

[0243] Example 3: Synthesis of thiocarbonyl lactide based on methyl methacrylate and formula (I-1) according to the method of the present invention Degradable copolymer CP3

[0244] 6.1 mg (0.025 mmol) of azobis(cyanocyclohexane) (VAZO-88), 0.08 g (0.5 mmol) of thiocarbonyl lactide (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. The thiocarbonyl lactide (monomer of formula (I-1)) accounted for 10% (by mole) relative to methyl methacrylate (monomer of formula (II)). The solution was transferred to a Carlos tube and sealed under vacuum after three degassing cycles. The tube was then placed in an oil bath at 100°C for 5 hours. The polymerization was stopped by rapid cooling. After opening the tube, part of the solution was transferred to an NMR tube to determine the conversion rate of the thiocarbonyl lactide (I-1) after 5 hours of reaction.

[0245] As described in Example 1, by H NMR spectroscopy ( 1H NMR) showed that the conversion of the thiocarbolide (I-1) monomer was 10%, and the conversion of the methyl methacrylate monomer was 64%. The residual monomers were evaporated, and the number average molar mass (Mn) and polydispersity index (Mw / Mn) of the poly(methyl methacrylate-co-thiocarbolide) copolymer CP3 were determined by size exclusion chromatography (eluent: THF) based on the PMMA calibration curve: Mn = 7000 g / mol; Mw / Mn = 1.9.

[0246] Example 4: Synthesis of a thiocarbonyl lactide based on vinyl pivalate and formula (I-1) according to the method of the present invention Degradable copolymer CP4

[0247] 5.4 mg (0.022 mmol) of azobis(cyanocyclohexane) (VAZO-88), 0.07 g (0.44 mmol) of thiocarbonyl lactide (I-1) obtained in Example 1, 0.504 g (3.9 mmol) of vinyl pivalate and 10 mg of naphthalene as an internal standard were mixed to form a solution. The thiocarbonyl lactide (monomer of formula (I-1)) accounted for 10% (by mole) relative to vinyl pivalate (monomer of formula (II)). The solution was transferred to a Carlos tube and sealed under vacuum after three degassing cycles. The tube was then placed in an oil bath at 70°C for 16 hours. The polymerization was stopped by rapid cooling. After opening the tube, part of the solution was transferred to an NMR tube to determine the conversion rate of the thiocarbonyl lactide (I-1) after 16 hours of reaction.

[0248] As described in Example 1, by H NMR spectroscopy ( 1 H NMR) showed that the conversion of the thiocarbolide (I-1) monomer was 100%, and the conversion of the vinyl pivalate monomer was 64%. The residual monomers were evaporated, and the number average molar mass (Mn) and polydispersity index (Mw / Mn) of the poly(vinyl pivalate-co-thiocarbolide) copolymer CP4 were determined by size exclusion chromatography (eluent: THF) based on the calibration curve of PMMA: Mn=12100 g / mol; Mw / Mn=2.1.

[0249] Example 5: Chemical Preparation of Degradable Copolymer CP2 Based on Tert-Butyl Acrylate and Thiocarbonyl Lactide of Formula (I-1) Chemical degradation

[0250] 10 mg of copolymer CP2 in Example 2 was diluted in 1 mL of THF, and 1 mL of bleach solution (NaOCl aqueous solution containing 11% to 15% active chlorine) was added. The resulting mixture was stirred 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 size exclusion chromatography.

[0251] Figure 1 CP2 before contact with bleach is shown (CP2 in THF, Mn = 8000 g / mole, Mw / Mn = 1.7, Figure 1 a) The residue obtained after contacting CP2 with bleach (Mn=2100 g / mol, Mw / Mn=1.5, Figure 1 b) and CP2 (Mn=6400 g / mol, Mw / Mn=2.0, Figure 1 c) The relative Δn value (i.e. the difference between the refractive index of the analyzed sample and the refractive index of the solvent) changes with the retention time (in minutes).

[0252] It appears that after degradation of copolymer CP2 by bleach, its molar mass distribution is strongly shifted to the low molar mass range compared to the copolymer before treatment, demonstrating that the degradation of the main chain is caused by the presence of thioester bonds.

[0253] Example 6: Synthesis of a thiocarbonyl lactide based on n-butyl acrylate and formula (I-1) according to the method of the present invention Degradable copolymer CP5

[0254] 4.3 mg (0.022 mmol) of azobis(isobutyronitrile) (AIBN), 0.07 g (0.44 mmol) of thiocarbonyl lactide (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 are mixed to form a solution. The thiocarbonyl lactide (monomer of formula (I-1)) accounts for 10% (by mole) relative to n-butyl acrylate (monomer of formula (II)). The solution is transferred to a Carlos tube and sealed under vacuum after three degassing cycles. The tube is then placed in an oil bath at 70°C for 3 hours. The polymerization is stopped by rapid cooling. After opening the tube, part of the solution is transferred to an NMR tube to determine the conversion rate of the thiocarbonyl lactide (I-1).

[0255] As described in Example 1, by H NMR spectroscopy ( 1 H NMR) showed that the conversion of the thiocarbolide (I-1) monomer was 41%, and the conversion of the n-butyl acrylate monomer was 87%. The residual monomers were evaporated, and the number average molar mass (Mn) and polydispersity index (Mw / Mn) of the poly(n-butyl acrylate-co-thiocarbolide) copolymer CP5 were determined by size exclusion chromatography (eluent: THF) based on the calibration curve of PMMA: Mn = 98000 g / mol; Mw / Mn = 1.7.

[0256] Example 7: Synthesis of dithiocarbonyl lactide based on tert-butyl acrylate and formula (I-2) according to the method of the present invention Degradable copolymer CP6

[0257] 7.1 Step 1: Synthesis of dithiocarbonyl lactide of formula (I-2)

[0258] P4S 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 double-necked flask with an overhead condenser. The resulting mixture was heated under reflux for 48 hours. The reaction medium was then cooled to room temperature, filtered through a layer of silica gel (50 g), and washed with dichloromethane (DCM). The filtrate was evaporated under reduced pressure and purified by column chromatography (eluent: 8 / 2 cyclohexane / ethyl acetate). Recrystallization was performed four times to obtain dithiocarbonyl lactide (I-2) crystals (0.1 g) in a yield of 2%. Before use in polymerization, the mixture was heated at 60° C. and 10 -2 The resulting crystals were sublimed under a pressure of mbar.

[0259] 1 H NMR (CDCl3, 300MHz) δ (ppm): 5,05 (q, 6.3Hz, 2H), 1,8 (d, 6, 3Hz, 6H).

[0260] 13 C NMR (CDCl3, 126MHz) δ (ppm): 211, 2, 78, 6, 19, 5.

[0261] 7.2 Step 2: Synthesizing a degradable copolymer CP6 based on tert-butyl acrylate and dithiocarbonyl lactide of formula (I-2) according to the method of the present invention

[0262] 5.3 mg (0.022 mmol) of azobis(cyanocyclohexane) (VAZO-88), 0.04 g (0.22 mmol) of dithiocarbonyl lactide (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. Dithiocarbonyl lactide (monomer of formula (I-2)) accounts for 5% (by mole) relative to tert-butyl acrylate (monomer of formula (II)). The solution was transferred to a Carlos tube and sealed under vacuum after three degassing cycles. The tube was then placed in an oil bath at 100°C for 5 hours. The polymerization was stopped by rapid cooling. After opening the tube, part of the solution was transferred to an NMR tube to measure the conversion rate of dithiocarbonyl lactide (I-2) after 5 hours of reaction.

[0263] H NMR ( 1 H NMR) is used to measure the conversion rate of monomers. For this reason, the signal integral of naphthalene at 7.8ppm as internal standard corresponds to 1, compared with the signal of 5.0ppm to 5.1ppm, the two hydrogen atoms of dithiocarbonyl lactide (I-2) corresponding to this signal, and compared with the integral result equal to 0 hour of reaction time. Therefore, the conversion rate of dithiocarbonyl lactide (I-2) after reaction X hours can be determined according to the following formula 2:

[0264]

[0265] By hydrogen nuclear magnetic resonance spectroscopy ( 1 H NMR) showed that the conversion of dithiocarbonyl lactide (I-2) monomer was 100%, and the conversion of tert-butyl acrylate monomer was 98%. The residual monomers were evaporated, and the number average molar mass (Mn) and polydispersity index (Mw / Mn) of the poly(tert-butyl acrylate-co-thiocarbonyl lactide) copolymer CP6 were determined by size exclusion chromatography (eluent: THF) based on the calibration curve of PMMA: Mn=28300 g / mol; Mw / Mn=2.5.

[0266] Example 8: Degradable copolymer CP6 based on tert-butyl acrylate and dithiocarbonyl lactide of formula (I-2) Chemical degradation

[0267] 10 mg of copolymer CP6 in Example 7 was diluted in 1 mL of THF, and 1 mL of bleach solution (NaOCl aqueous solution containing 11% to 15% active chlorine) was added. The resulting mixture was stirred 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 size exclusion chromatography.

[0268] 10 mg of copolymer CP6 in Example 7 was diluted in 1 mL of THF, and 1 mL of isopropylamine solution was added. The resulting mixture was stirred in a sealed tube at room temperature for 30 days. The solvent and isopropylamine were evaporated under reduced pressure, and the residue was then dissolved in THF and analyzed by size exclusion chromatography.

[0269] Figure 2 CP6 (Mn = 28300 g / mole, Mw / Mn = 2.5, Figure 2 a) The residue obtained after contacting CP6 with bleach (Mn=7700 g / mol, Mw / Mn=3.5, Figure 2 b) and the residue obtained after contacting CP6 with isopropylamine (Mn=8200 g / mol, Mw / Mn=2.8, Figure 2 c) The relative Δn value (i.e. the difference between the refractive index of the analyzed sample and the refractive index of the solvent) changes with the retention time (in minutes).

[0270] It appears that after degradation of copolymer CP6 by bleach or isopropylamine, its molar mass distribution is strongly shifted to the low molar mass range compared to the copolymer before treatment, demonstrating that the degradation of the main chain is caused by the presence of thioester bonds.

[0271] Example 9: Synthesis of dithiocarbonyl crosslinked compounds based on methyl methacrylate and formula (I-2) according to the method of the present invention Degradable copolymer of ester CP7

[0272] 5.5 mg (0.023 mmol) of azobis(cyanocyclohexane) (VAZO-88), 0.04 g (0.23 mmol) of dithiocarbonyl lactide (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. The dithiocarbonyl lactide (monomer of formula (I-2)) accounted for 5% (by mole) relative to methyl methacrylate (monomer of formula (II)). The solution was transferred to a Carlos tube and sealed under vacuum after three degassing cycles. The tube was then placed in an oil bath at 100°C for 5 hours. The polymerization was stopped by rapid cooling. After opening the tube, part of the solution was transferred to an NMR tube to determine the conversion rate of dithiocarbonyl lactide (I-2) after 5 hours of reaction.

[0273] As described in Example 7.2, by H NMR spectroscopy ( 1 H NMR) showed that the conversion of dithiocarbonyl lactide (I-2) monomer was 20%, and the conversion of methyl methacrylate monomer was 80%. The residual monomers were evaporated, and the number average molar mass (Mn) and polydispersity index (Mw / Mn) of the poly(methyl methacrylate-co-dithiocarbonyl lactide) copolymer CP7 were determined by size exclusion chromatography (eluent: THF) based on the calibration curve of PMMA: Mn = 15000 g / mol; Mw / Mn = 2.7.

[0274] Example 10: Synthesis of thiocarbonyl lactide of formula (I-3)

[0275] P4S 10 The mixture was heated at reflux for 5 hours. The reaction medium was then cooled to room temperature and the solvent was evaporated. The product was purified for the first time by column chromatography (dichloromethane eluent) and then the collected fractions were purified again by column chromatography (50 g silica gel, eluent: 30% ether / 70% petroleum ether) to give a yield of 20% (1.1 g).

[0276] 1 H NMR (CDCl3, 300MHz) δ (ppm): 5, 2 (s, 4H).

[0277] 13 C NMR (CDCl3, 126MHz) δ (ppm): 206, 165, 78, 73.

[0278] Example 11: Synthesis of thiocarbonyl lactide based on tert-butyl acrylate and formula (I-13) according to the method of the present invention Degradable copolymer CP8

[0279] 11.1 Step 1: Synthesis of 3,3-dimethyl glycolide

[0280] 9.2g (88.5 mmoles) of α-hydroxyisobutyric acid and 10g of chloroacetyl chloride (88.5 mmoles) were added to 20mL of anhydrous acetonitrile in a double-necked flask with an overhead condenser. The mixture was heated to 80°C and stirred overnight. After cooling to room temperature, the reaction mixture was diluted with 200mL of acetonitrile and 17.9g of triethylamine (177 mmoles) was added dropwise. The resulting solution was added to 80°C for 6 hours. After filtration, the solvent was evaporated to obtain a product (5.1g) with a yield of 40%.

[0281] 1 H NMR (CDCl3, 300MHz): δ (ppm): 1.67 (s, 6H); 5.01 (s, 2H).

[0282] 13 C NMR (CDCl3, 126MHz) δ (ppm): 167, 164, 75, 73, 24.

[0283] 11.2 Step 2: Synthesis of 3,3-dimethylthiocarbonylglycolide of thiocarbonyllide of formula (I-13)

[0284] P4S 10 (8.7 mmol, 3.9 g), 3,3-dimethyl glycolide from Example 11.1 (34.7 mmol, 5 g), hexamethyldisiloxane (HMDSO) (58.0 mmol, 9.4 g) and 50 mL of anhydrous acetonitrile were introduced into a two-necked flask with an overhead condenser and the entire flask was inertized by bubbling argon. The resulting mixture 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 purified for a first time by column chromatography (dichloromethane eluent) and the collected fractions were then purified again by column chromatography (50 g of silica gel, eluent: 30% ether / 70% petroleum ether) to give a yield of 20% (1.8 g).

[0285] 1 H NMR (CDCl3, 300MHz): 5.2ppm (s, 2H), 1.76ppm (s, 6H).

[0286] 13 C NMR (CDCl3, 126MHz): 206,2,167,7,82,5,73,8,25,2.

[0287] Figure 3 The crystal structure of thiocarbolide (I-13) is shown.

[0288] 11.3 Step 3: Synthesizing a degradable copolymer CP8 based on tert-butyl acrylate and thiocarbonyl lactide of formula (I-13) according to the method of the present invention

[0289] 5.3 mg (0.022 mmol) of azobis(cyanocyclohexane) (VAZO-88), 0.07 g (0.44 mmol) of thiocarbonyl lactide (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. The thiocarbonyl lactide (monomer of formula (I-13)) accounted for 10% (by mole) relative to tert-butyl acrylate (monomer of formula (II)). After three degassing cycles, the solution was transferred to a Carlos tube. The tube was then placed in an oil bath at 100°C for 5 hours. The polymerization was stopped by rapid cooling. After opening the tube, part of the solution was transferred to an NMR tube to determine the conversion rate of the thiocarbonyl lactide (I-13) after 5 hours of reaction.

[0290] H NMR ( 1 H NMR) is used to measure the transformation efficiency of monomer. For this reason, the signal integral of naphthalene at 7.8ppm as internal standard corresponds to 1, and the signal of 5.3ppm to 5.1ppm is compared, and the two hydrogen atoms of thiocarbonyl lactide (I-13) of this signal correspondence, and the integral result equal to 0 hour with the reaction time is compared. Therefore, the transformation efficiency of thiocarbonyl lactide (I-13) after reaction X hours can be determined according to the following formula 3:

[0291]

[0292] By hydrogen nuclear magnetic resonance spectroscopy ( 1 H NMR) showed that the conversion of the thiocarbolide (I-13) monomer was 44%, and the conversion of the tert-butyl acrylate monomer was 82%. The residual monomers were evaporated, and the number average molar mass (Mn) and polydispersity index (Mw / Mn) of the poly(tert-butyl acrylate-co-thiocarbolide) copolymer CP8 were determined by size exclusion chromatography (eluent: THF) based on the calibration curve of PMMA: Mn = 13800 g / mol; Mw / Mn = 2.4.

[0293] Example 12: Degradable copolymer CP8 based on tert-butyl acrylate and thiocarbonyl lactide of formula (I-13) Chemical degradation

[0294] 10 mg of copolymer CP8 in Example 11.3 was diluted in 1 mL of THF, and 1 mL of bleach solution (NaOCl aqueous solution containing 11% to 15% active chlorine) was added. The resulting mixture was stirred 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 size exclusion chromatography.

[0295] Figure 4 CP8 before degradation is shown (CP8 in THF, Mn = 13800 g / mole, Mw / Mn = 2.4, Figure 4 a) and the residue obtained after contacting CP8 with bleach (Mn=3300 g / mole, Mw / Mn=1.6, Figure 4 b) The relative Δn value (i.e. the difference between the refractive index of the analyzed sample and the refractive index of the solvent) changes with the retention time (in minutes).

[0296] It appears that after degradation of copolymer CP8 by bleach, its molar mass distribution is strongly shifted to the low molar mass range compared to the copolymer before treatment, demonstrating that the degradation of the main chain is caused by the presence of thioester bonds.

[0297] Example 13: Synthesis of a thiocarbonyl crosslinked compound based on methyl methacrylate and formula (I-13) according to the method of the present invention Degradable copolymer of ester CP9

[0298] 6.1 mg (0.025 mmol) of azobis(cyanocyclohexane) (VAZO-88), 0.08 g (0.5 mmol) of thiocarbonyl lactide (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. The thiocarbonyl lactide (monomer of formula (I-13)) accounted for 10% (by mole) relative to methyl methacrylate (monomer of formula (II)). The solution was transferred to a Carlos tube and sealed under vacuum after three degassing cycles. The tube was then placed in an oil bath at 100°C for 5 hours. The polymerization was stopped by rapid cooling. After opening the tube, part of the solution was transferred to an NMR tube to determine the conversion rate of the thiocarbonyl lactide (I-13) after 5 hours of reaction.

[0299] As described in Example 11.2, by H NMR spectroscopy ( 1 H NMR) showed that the conversion of the thiocarbolide (I-13) monomer was 25%, and the conversion of the methyl methacrylate monomer was 90%. The residual monomers were evaporated, and the number average molar mass (Mn) and polydispersity index (Mw / Mn) of the poly(methyl methacrylate-co-thiocarbolide) copolymer CP9 were determined by size exclusion chromatography (eluent: THF) based on the calibration curve of PMMA: Mn = 13900 g / mol; Mw / Mn = 2.0.

[0300] Example 14: Synthesis of thiocarbonyl lactide based on tert-butyl acrylate and formula (I-14) according to the method of the present invention Degradable copolymer CP10

[0301] 14.1 Step 1: Synthesis of 3,3,6-trimethylglycolide

[0302] 8.2g (78.7 mmoles) of α-hydroxyisobutyric acid and 10g of chloropropyl chloride (78.7 mmoles) are added to 20mL of anhydrous acetonitrile in a double-necked flask with an overhead condenser. The mixture is heated to 80°C and stirred overnight. After cooling to room temperature, the reaction mixture is diluted with 200mL of acetonitrile and 15.9g of triethylamine (157.5 mmoles) is added dropwise. The resulting solution is added to 80°C for 6 hours. After filtration, the solvent is evaporated to obtain the product (4.4g) in a yield of 40%.

[0303] 1 H NMR (CDCl3, 300MHz) δ (ppm): 1.68 (m, 9H); 5.09 (q, 7, 2Hz, 1H).

[0304] 13 C NMR (CDCl3, 126MHz) δ (ppm): 168,8, 166,8, 80,7, 73, 1, 26,4, 25,4, 17,6.

[0305] 14.2 Step 2: Synthesis of 3,3,6-trimethylthiocarbonylglycolide of thiocarbonyllide of formula (I-14)

[0306] P4S 10 (4.7 mmol, 2.1 g), 3,3,6-trimethyl glycolide from Example 14.1 (19 mmol, 3 g), hexamethyldisiloxane (HMDSO) (31.7 mmol, 5.1 g) and 50 mL of anhydrous acetonitrile were introduced into a two-necked flask with an overhead condenser and the entire flask was rendered inert by bubbling argon. The resulting mixture 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 purified for a first time by column chromatography (dichloromethane eluent) and the collected fractions were then purified again by column chromatography (50 g of silica gel, eluent: 20% ether / 80% petroleum ether) to give a yield of 25% (0.8 g).

[0307] 1 H NMR (CDCl3, 300MHz) δ (ppm): 5,2 (q, 6, 6Hz, 1H), 1,87 (d, 6, 6Hz, 3H), 1,79 (s, 6H).

[0308] 13 C NMR (CDCl3, 126MHz) δ (ppm): 211, 4, 169, 0, 83, 2, 79, 6, 24, 7, 21, 5.

[0309] Figure 5 The crystal structure of thiocarbolide (I-14) is shown.

[0310] 14.3 Step 3: Synthesizing a degradable copolymer CP10 based on tert-butyl acrylate and thiocarbonyl lactide of formula (I-14) according to the method of the present invention

[0311] 5 mg (0.02 mmol) of azobis(cyanocyclohexane) (VAZO-88), 0.07 g (0.40 mmol) of thiocarbonyl lactide (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. The thiocarbonyl lactide (monomer of formula (I-14)) accounted for 10% (by mole) relative to tert-butyl acrylate (monomer of formula (II)). The solution was transferred to a Carlos tube and sealed under vacuum after three degassing cycles. The tube was then placed in an oil bath at 100°C for 5 hours. The polymerization was stopped by rapid cooling. After opening the tube, part of the solution was transferred to an NMR tube to determine the conversion rate of the thiocarbonyl lactide (I-14) after 5 hours of reaction.

[0312] H NMR ( 1 H NMR) is used to measure the conversion rate of monomers. For this reason, the signal integral of naphthalene at 7.8ppm as internal standard corresponds to 1, and is compared with the signal of 5.1ppm to 4.9ppm, which corresponds to two hydrogen atoms of thiocarbonyl lactide (I-14), and is compared with the integral result equal to 0 hour of reaction time. Therefore, the conversion rate of thiocarbonyl lactide (I-14) after reaction X hours can be determined by the following formula 4:

[0313]

[0314] By hydrogen nuclear magnetic resonance spectroscopy ( 1 H NMR) showed that the conversion of the thiocarbolide (I-14) monomer was 26%, and the conversion of the tert-butyl acrylate monomer was 52%. The residual monomers were evaporated, and the number average molar mass (Mn) and polydispersity index (Mw / Mn) of the poly(tert-butyl acrylate-co-thiocarbolide) copolymer CP10 were determined by size exclusion chromatography (eluent: THF) based on the calibration curve of PMMA: Mn = 13500 g / mol; Mw / Mn = 4.2.

[0315] Example 15: Degradable copolymer CP10 based on tert-butyl acrylate and thiocarbonyl lactide of formula (I-14) Chemical degradation

[0316] 10 mg of copolymer CP10 in Example 14.3 was diluted in 1 mL of THF, and 1 mL of bleach solution (NaOCl aqueous solution containing 11% to 15% active chlorine) was added. The resulting mixture was stirred 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 size exclusion chromatography.

[0317] Figure 6 CP10 before contact with bleach is shown (CP10 in THF, Mn = 13500 g / mole, Mw / Mn = 3.8, Figure 6 a) and the residue obtained after contacting CP8 with bleach (Mn=5700 g / mole, Mw / Mn=1.9, Figure 6 b) The relative Δn value (i.e. the difference between the refractive index of the analyzed sample and the refractive index of the solvent) changes with the retention time (in minutes).

[0318] It appears that after degradation of copolymer CP10 by bleach, its molar mass distribution is strongly shifted to the low molar mass range compared to the copolymer before treatment, demonstrating that the degradation of the main chain is caused by the presence of thioester bonds.

[0319] Example 16: Synthesis of a thiocarbonyl crosslinked compound based on methyl methacrylate and formula (I-14) according to the method of the present invention Degradable copolymer of ester CP11

[0320] 5.6 mg (0.023 mmol) of azobis(cyanocyclohexane) (VAZO-88), 0.08 g (0.46 mmol) of thiocarbonyl lactide (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. The thiocarbonyl lactide (monomer of formula (I-14)) accounted for 10% (by mole) relative to methyl methacrylate (monomer of formula (II)). The solution was transferred to a Carlos tube and sealed under vacuum after three degassing cycles. The tube was then placed in an oil bath at 100°C for 5 hours. The polymerization was stopped by rapid cooling. After opening the tube, part of the solution was transferred to an NMR tube to determine the conversion rate of the thiocarbonyl lactide (I-14) after 5 hours of reaction.

[0321] As described in Example 14.3, by H NMR spectroscopy ( 1 H NMR) showed that the conversion of the thiocarbolide (I-14) monomer was 15%, and the conversion of the methyl methacrylate monomer was 28%. The residual monomers were evaporated, and the number average molar mass (Mn) and polydispersity index (Mw / Mn) of the poly(methyl methacrylate-co-thiocarbolide) copolymer CP11 were determined by size exclusion chromatography (eluent: THF) based on the calibration curve of PMMA: Mn = 2400 g / mol; Mw / Mn = 1.4.

[0322] Example 17: Synthesis of a reducible thiocarbonyl lactide based on styrene and formula (I-14) according to the method of the present invention Depolymer CP12

[0323] 5 mg (0.020 mmol) of azobis(cyanocyclohexane) (VAZO-88), 0.07 g (0.4 mmol) of thiocarbonyl lactide (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. The thiocarbonyl lactide (monomer of formula (I-14)) accounted for 10% (by mole) relative to styrene (monomer of formula (II)). The solution was transferred to a Carlos tube and sealed under vacuum after three degassing cycles. The tube was then placed in an oil bath at 100°C for 5 hours. The polymerization was stopped by rapid cooling. After opening the tube, part of the solution was transferred to an NMR tube to determine the conversion rate of the thiocarbonyl lactide (I-14) after 5 hours of reaction.

[0324] As described in Example 14.3, by H NMR spectroscopy ( 1 H NMR) showed that the conversion of the thiocarbonyl lactide (I-14) monomer was 26%, and the conversion of the styrene monomer was 46%. The residual monomers were evaporated, and the number average molar mass (Mn) and polydispersity index (Mw / Mn) of the copolymer CP12 were determined by size exclusion chromatography (eluent: tetrahydrofuran THF) based on the calibration curve of 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, comprising at least one step of free radical polymerization by ring opening of at least one cyclic monomer using at least one monomer containing ethylenically unsaturated bonds in the presence of a free radical polymerization initiator, characterized in that: (i) The cyclic monomer is selected from the thiocarbonyl lactide of the following formula (I): in: -X is an oxygen atom or a sulfur atom; -R 1 , R 2 , R 3 and R 4 Each independently represents a hydrogen atom, a halogen atom, a group selected from the following groups: an alkyl radical, a haloalkyl radical, an optionally substituted phenyl radical, a cyano group, an optionally substituted alkyl-phenyl radical, an optionally substituted haloalkyl-phenyl radical, a carboxylic acid radical, an R having an alkyl radical 5 Ester radical CO2R 5 , phosphonic acid radical, R having a hydrogen atom or an alkyl radical 6a and R representing an alkyl radical 6b The phosphonate radical P(O)(OR 6a )(OR 6b ), sulfonic acid radical, R representing an alkyl radical or a halogenated alkyl radical 7 Sulfonate radical SO3R 7 , and R each independently represents a hydrogen atom or an alkyl radical or together forms an alkyl radical 8a and R 8b The amide radical C(O)NR 8a R 8b ; And the characteristics are: (ii) The monomer containing an ethylene unsaturated bond is selected from the monomer of the following formula (II): in: -R 9 represents a hydrogen atom or a fluorine atom; -R 10 represents a hydrogen atom or a fluorine atom; -R 11 represents a hydrogen atom, an alkyl radical, a fluorine atom or a chlorine atom; -R 12 represents a hydrogen atom, or a group selected from the following groups: *Alkyl radicals, *Haloalkyl radicals, * an optionally substituted aryl radical, *optionally substituted alkyl-aryl radicals; *Imidazole, *Alkyl imidazole base, *Carbazolyl, * A group of the following formula (III): The asterisk (*) indicates the binding site of the group of formula (III) to the carbon atom of the compound of formula (II), and the same or different R 13 and R 14 represents a hydrogen atom, an alkyl radical, an optionally substituted alkyl-aryl radical, an optionally substituted aryl radical, a glycidyl group, or R 13 and R 14 The nitrogen atom and the carbon atom of the radical of formula (III) to which it is bonded together form a heterocarbocyclic ring containing 4 to 7 carbon atoms, *-OC(O)R 15 Group, where R 15 represents an alkyl radical, a haloalkyl radical, an optionally substituted alkyl-aryl radical, an optionally substituted aryl radical, *-C(O)OR 16 Group, where R 16 represents an alkyl radical, a haloalkyl radical, an optionally substituted alkyl-aryl radical or an optionally substituted aryl radical, *Phosphonic acid group, *Phosphonate group P(O)(OR 17a )(OR 17b ), where R 17a represents a hydrogen atom or an alkyl radical, and R 17b represents an alkyl radical, *Sulfonic acid group, *Sulfonate group SO3R 18 , where R 18 represents an alkyl radical or a haloalkyl radical, and *Amide group C(O)NR 19a R 19b , where R 19a and R 19b Each independently represents a hydrogen atom or an alkyl radical, or together forms an alkyl radical.

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

3. The method according to claim 1 or 2, characterized in that: *R 1 =H or CH3, *R 2 =H, CH3, C6H5, CF3, C6F5, C6H4-CF3, F, CH2F, CH2Cl or C2H4-Cl, *R 3 =H or CH3, *R 4 =H, CH3, C6H5, CF3, C6F5, C6H4-CF3, F, CH2F, CH2Cl or C2H4-Cl.

4. The method according to any one of the preceding claims, characterized in that The thiocarbonyl lactide of formula (I) is selected from the following thiocarbonyl lactides: (i) thiocarbonyl lactide, wherein R 2 and R 4 As defined in claim 1, excluding hydrogen atoms, (ii) thiocarbonyl lactide, wherein R 3 and R 4 As defined in claim 1, excluding hydrogen atoms, and (iii) thiocarbonyl lactide, wherein R 1 , R 2 , R 3 or R 4 A hydrogen atom.

5. The method according to any one of the preceding claims, characterized in that The thiocarbonyl lactide of formula (I) is selected from the thiocarbonyl lactides of formula (I-1) to formula (I-13) shown in Table 1 below: Table 1.

6. The method according to any one of the preceding claims, characterized in that R 9 represents a hydrogen atom, R 10 represents a hydrogen atom, and R 11 represents a hydrogen atom or an alkyl radical.

7. The method according to any one of the preceding claims, characterized in that The monomer of formula (II) is selected from: * Vinyl ester monomer represented by the following formula (II-1): *α-olefin monomer represented by the following formula (II-2): Where R 11 represents a hydrogen atom or an alkyl radical, and R 12 represents an alkyl radical or an optionally substituted aryl radical, *N-vinyl type monomer represented by the following formula (III-1): *Acrylate type monomer and alkylacrylate type monomer represented by the following formula (II-3): Where R 11 represents a hydrogen atom or an alkyl radical, and R 16 represents an alkyl radical.

8. The method according to any one of the preceding claims, characterized in that The proportions of the monomers of formula (I) are chosen such that the amount of one or more than one monomer of formula (I) is at most 50% relative to the total amount of monomers of formula (I) and formula (II).

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

10. The method according to any one of the preceding claims, characterized in that The polymerization is carried out in a solvent, and the total amount of the monomers of formula (I) and formula (II) is 30% to 60% by mass relative to the total mass of the reaction medium.

11. The method according to any one of the preceding claims, characterized in that The polymerization step is carried out at a temperature ranging from 5°C to 150°C.

12. A copolymer, preferably a degradable copolymer, characterized in that it contains at least thioester bonds and is produced by free radical polymerization in the presence of a free radical polymerization initiator by ring opening of the following monomers: (i) at least one cyclic monomer selected from the group consisting of thiocarbonyl lactide of formula (I): in: -X is an oxygen atom or a sulfur atom; -R 1 , R 2 , R 3 and R 4 Each independently represents a hydrogen atom, a halogen atom, a group selected from the following groups: an alkyl radical, a haloalkyl radical, an optionally substituted phenyl radical, a cyano group, an optionally substituted alkyl-phenyl radical, an optionally substituted haloalkyl-phenyl radical, a carboxylic acid radical, an R having an alkyl radical 5 Ester radical CO2R 5 , phosphonic acid radical, R having a hydrogen atom or an alkyl radical 6a and R representing an alkyl radical 6b The phosphonate radical P(O)(OR 6a )(OR 6b ), sulfonic acid radical, R representing an alkyl radical or a halogenated alkyl radical 7 Sulfonate radical SO3R 7 , and R each independently represents a hydrogen atom or an alkyl radical or together forms an alkyl radical 8a and R 8b The amide radical C(O)NR 8a R 8b ;and (ii) at least one monomer containing an ethylenically unsaturated bond selected from monomers of the following formula (II): in: -R 9 represents a hydrogen atom or a fluorine atom; -R 10 represents a hydrogen atom or a fluorine atom; -R 11 represents a hydrogen atom, an alkyl radical, a fluorine atom or a chlorine atom; -R 12 represents a hydrogen atom, or a group selected from the following groups: *Alkyl radicals, *Haloalkyl radicals, * an optionally substituted aryl radical, *optionally substituted alkyl-aryl radicals; *Imidazole, *Alkyl imidazole base, *Carbazolyl, * A group of the following formula (III): The asterisk (*) indicates the binding site of the group of formula (III) to the carbon atom of the compound of formula (II), and the same or different R 13 and R 14 represents a hydrogen atom, an alkyl radical, an optionally substituted alkyl-aryl radical, an optionally substituted aryl radical, a glycidyl group, or R 13 and R 14 The nitrogen atom and the carbon atom (including the carbon atom carrying the oxygen atom) of the radical of formula (III) to which it is bonded together form a heterocarbocyclic ring containing 4 to 7 carbon atoms, *-OC(O)R 15 Group, where R 15 represents an alkyl radical, a haloalkyl radical, an optionally substituted alkyl-aryl radical, an optionally substituted aryl radical, *-C(O)OR 16 Group, where R 16 represents an alkyl radical, a haloalkyl radical, an optionally substituted alkyl-aryl radical or an optionally substituted aryl radical, *Phosphonic acid group, *Phosphonate group P(O)(OR 17a )(OR 17b ), where R 17a represents a hydrogen atom or an alkyl radical, and R 17b represents an alkyl radical, *Sulfonic acid group, *Sulfonate group SO3R 18 , where R 18 represents an alkyl radical or a haloalkyl radical, and *Amide group C(O)NR 19a R 19b , where R 19a and R 19b Each independently represents a hydrogen atom or an alkyl radical, or together forms an alkyl radical.

13. The copolymer according to claim 12, characterized in that The copolymer is produced by polymerizing thiocarbonyl lactide (I-1) as defined in claim 5 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 main chain is at least 2% by number relative to the total number of bonds in the main chain.

15. Use of at least one thiocarbolide of formula (I) as defined in any one of claims 1 to 5 as a precursor monomer for a free-radical polymerization.

16. A thiocarbonyl lactide for use in carrying out a process as defined in any one of claims 1 to 11 and having the following formula (I'): in: -X, R 1 , R 2 , R 3 and R 4 As defined in any one of claims 1 to 5, - excluding thiocarbolide (I-1) and thiocarbolide (I-2) as defined in claim 5.

17. The thiocarbonyl lactide according to claim 16, which is selected from the thiocarbonyl lactides of formula (I-3) to formula (I-13) as defined in claim 5.

Images