METHOD FOR PREPARING THIOLACTONES, THIOLACTONES OBTAINED BY SAID METHOD AND USES THEREOF

Abstract

The present invention relates to a process for the preparation of substituted thiolactones of formula (I) or of substituted thiolactones of formula (I) which are capable of being obtained by the implementation of this process, and to the use of substituted thiolactones of formula (I) or of formula (I) in the preparation of polymers or in the functionalization of particles, of flat surfaces or of polymers.

Claims

1. Process for the preparation of substituted thiolactones of following formula (I): ##STR00024## in which: R.sup.1, R.sup.2, R.sup.3 and R.sup.4, which are identical or different, represent a hydrogen atom or a group chosen from alkyl, acyl, aryl, heteroaryl, saturated or unsaturated cycloalkyl and saturated or unsaturated heterocycloalkyl groups, it also being possible for the R.sup.1, R.sup.2, R.sup.3 and R.sup.4 radicals to together form a saturated or unsaturated cycloalkyl or heterocycloalkyl group or an aryl or heteroaryl group; and R.sup.5, R.sup.6 and R.sup.7, which are identical or different, are: (a) chosen from a hydrogen atom, a cyano (CN) group, an alkyl group, an acyl group, an aryl group, a heteroaryl group, an aralkyl group, a saturated or unsaturated cycloalkyl group, a saturated or unsaturated heterocycloalkyl group and a phthalimido group, it being possible for said alkyl, acyl, aryl, heteroaryl, aralkyl, saturated or unsaturated cycloalkyl, saturated or unsaturated heterocycloalkyl and phthalimido groups to be substituted by an X group chosen from the following groups: P(O)(OR.sup.8)(OR.sup.8), in which the R.sup.8 and R.sup.8 radicals, which are identical or different, represent a hydrogen atom or an alkyl radical; C.sub.nF.sub.2n+1, in which n is an integer ranging from 1 to 20; SiR.sup.9.sub.p(OR.sup.10).sub.3-p, in which the R.sup.9 and R.sup.10 radicals, which are identical or different, represent a hydrogen atom or an alkyl radical and p is an integer equal to 0, 1 or 2; BF.sub.3M, in which M=K or Na; B(OR.sup.11).sub.2, in which the two R.sup.11 radicals, which are identical or different, represent a hydrogen atom, an alkyl radical or form a carbon-based ring with the two oxygen atoms to which they are bonded; OR.sup.12, in which R.sup.12 represents a hydrogen atom or an alkyl, aryl or aralkyl radical; O(CO)R.sup.13, in which R.sup.13 represents a hydrogen atom or an alkyl, aryl or aralkyl radical; O(CO)OR.sup.14, in which R.sup.14 represents a hydrogen atom or an alkyl, aryl or aralkyl radical; N.sup.+R.sup.15R.sup.15R.sup.15A.sup., in which the R.sup.15, R.sup.15 and R.sup.15 radicals, which are identical or different, represent a hydrogen atom or an alkyl, aryl or aralkyl radical and A represents a chlorine or bromine atom; NR.sup.16(CO)R.sup.16, in which the R.sup.16 and R.sup.16 radicals, which are identical or different, represent a hydrogen atom or an alkyl or aryl radical or are connected together and form a ring, such as a pyrrolidone or caprolactam ring; NR.sup.17(CO)OR.sup.17, in which R.sup.17 and R.sup.17, which are identical or different, represent a hydrogen atom or an alkyl, aryl or aralkyl radical; CN; a halogen atom chosen from Cl, F and Br; NCS; OCH.sub.2-epoxy; COOR.sup.18, in which R.sup.18 represents a hydrogen atom or an alkyl, aryl or aralkyl radical; CONR.sup.19R.sup.19, in which R.sup.19 and R.sup.19, which are identical or different, represent a hydrogen atom or an alkyl or aryl radical; SO.sub.2R.sup.20, in which R.sup.20 represents an alkyl or aryl radical; azide (N.sub.3) and alkynyl; or (b) such that they together form a polymer chain P.sup.1, or (c) such that R.sup.5 is different from the other two groups R.sup.6 and R.sup.7, R.sup.6 and R.sup.7 have the same definitions as in the alternative (a) and R.sup.5 is a thiolactone radical of following formula: ##STR00025## in which R.sup.1, R.sup.2, R.sup.3 and R.sup.4 have the same meanings as in the formula (I) above, R.sup.6 and R.sup.7 have the same definitions as in the alternative (a), Z represents a divalent group chosen from a carbonyl group, a carbonate group, an alkylene group and an arylene group, and the sign # represents the point of attachment of the thiolactone radical to the CR.sup.6R.sup.7CH.sub.2-thiolactone radical of the compound of formula (I); wherein said comprises at least the following stages: 1) a stage during which a xanthate of following formula (II): ##STR00026## in which: R.sup.21, R.sup.22, R.sup.23 and R.sup.24, which are identical or different, represent a hydrogen atom or a group chosen from alkyl, acyl, aryl, heteroaryl, alkenyl, alkynyl, saturated or unsaturated cycloalkyl and saturated or unsaturated heterocycloalkyl groups, it also being possible for the R.sup.21, R.sup.22, R.sup.23 and R.sup.24 radicals to together form a saturated or unsaturated cycloalkyl or heterocycloalkyl group or an aryl or heteroaryl group; and R.sup.5a, R.sup.6 and R.sup.7, which are identical or different, are: (a) chosen from a hydrogen atom, a cyano (CN) group, an alkyl group, an acyl group, an aryl group, a heteroaryl group, an aralkyl group, a saturated or unsaturated cycloalkyl group, a saturated or unsaturated heterocycloalkyl group and a phthalimido group, it being possible for said alkyl, acyl, aryl, heteroaryl, aralkyl, saturated or unsaturated cycloalkyl, saturated or unsaturated heterocycloalkyl and phthalimido groups to be substituted by an X group chosen from the following groups: P(O)(OR.sup.8)(OR.sup.8), in which the R.sup.8 and R.sup.8 radicals, which are identical or different, represent a hydrogen atom or an alkyl radical; C.sub.nF.sub.2n+1, in which n is an integer ranging from 1 to 20; SiR.sup.9.sub.p(OR.sup.10).sub.3-p, in which the R.sup.9 and R.sup.10 radicals, which are identical or different, represent a hydrogen atom or an alkyl radical and p is an integer equal to 0, 1 or 2; BF.sub.3M, in which M=K or Na; B(OR.sup.11).sub.2, in which the two R.sup.11 radicals, which are identical or different, represent a hydrogen atom, an alkyl radical or form a carbon-based ring with the two oxygen atoms to which they are bonded; OR.sup.12, in which R.sup.12 represents a hydrogen atom or an alkyl, aryl or aralkyl radical; O(CO)R.sup.13, in which R.sup.13 represents a hydrogen atom or an alkyl, aryl or aralkyl radical; O(CO)OR.sup.14, in which R.sup.14 represents a hydrogen atom or an alkyl, aryl or aralkyl radical; N+R.sup.15R.sup.15R.sup.15A.sup., in which the R.sup.15, R.sup.15 and R.sup.15 radicals, which are identical or different, represent a hydrogen atom or an alkyl, aryl or aralkyl radical and A represents a chlorine or bromine atom; NR.sup.16(CO)R.sup.16, in which the R.sup.16 and R.sup.16 radicals, which are identical or different, represent a hydrogen atom or an alkyl or aryl radical or are connected together and form a ring, such as a pyrrolidone or caprolactam ring; NR.sup.17(CO)OR.sup.17, in which R.sup.17 and R.sup.17, which are identical or different, represent a hydrogen atom or an alkyl, aryl or aralkyl radical; CN; a halogen atom chosen from Cl, F and Br; NCS; OCH.sub.2-epoxy; COOR.sup.18, in which R.sup.18 represents a hydrogen atom or an alkyl, aryl or aralkyl radical; CONR.sup.19R.sup.19, in which R.sup.19 and R.sup.19, which are identical or different, represent a hydrogen atom or an alkyl or aryl radical; SO.sub.2R.sup.20, in which R.sup.20 represents an alkyl or aryl radical; azide (N.sub.3) and alkynyl; or (b) such that they together form a polymer chain P.sup.1; or (c) such that R.sup.5a is different from the other two groups R.sup.6 and R.sup.7, R.sup.6 and R.sup.7 have the same definitions as in the alternative (a) and R.sup.5a is a xanthate radical of formula: ##STR00027## in which R.sup.21, R.sup.22, R.sup.23 and R.sup.24 have the same meanings as in the formula (II) above, R.sup.6 and R.sup.7 have the same definitions as in the alternative (a), Z represents a divalent group chosen from a carbonyl group, a carbonate group, an alkylene group and an arylene group, and the sign # represents the point of attachment of the xanthate radical to the CR.sup.6R.sup.7-xanthate radical of the compound of formula (II); is reacted, in the presence of a radical initiator, with a monomer comprising at least one ethylenic unsaturation of following formula (III): ##STR00028## in which: R.sup.25 represents a group chosen from alkyl, acyl, aryl, heteroaryl, aralkyl, saturated or unsaturated cycloalkyl and saturated or unsaturated heterocycloalkyl groups; Y is an oxygen atom or an NR.sup.26 radical in which R.sup.26 represents a hydrogen atom or an alkyl group, and preferably an oxygen atom; and R.sup.1, R.sup.2, R.sup.3 and R.sup.4 have the same meanings as in the formula (I) above; to form a monoadduct of following formula (IV): ##STR00029## in which: R.sup.1, R.sup.2, R.sup.3 and R.sup.4 have the same meanings as in the formula (I) above; R.sup.21, R.sup.22, R.sup.23 and R.sup.24 have the same meanings as in the formula (II) above; and R.sup.25 has the same meaning as in the formula (III) above; and R.sup.5b, R.sup.6 and R.sup.7, which are identical or different, are: (a) chosen from a hydrogen atom, a cyano (CN) group, an alkyl group, an acyl group, an aryl group, a heteroaryl group, an aralkyl group, a saturated or unsaturated cycloalkyl group, a saturated or unsaturated heterocycloalkyl group and a phthalimido group, it being possible for said alkyl, acyl, aryl, heteroaryl, aralkyl, saturated or unsaturated cycloalkyl, saturated or unsaturated heterocycloalkyl and phthalimido groups to be substituted by an X group chosen from the following groups: P(O)(OR.sup.8)(OR.sup.8), in which the R.sup.8 and R.sup.8 radicals, which are identical or different, represent a hydrogen atom or an alkyl radical; C.sub.nF.sub.2n+1, in which n is an integer ranging from 1 to 20; SiR.sup.9.sub.p(OR.sup.10).sub.3-p, in which the R.sup.9 and R.sup.10 radicals, which are identical or different, represent a hydrogen atom or an alkyl radical and p is an integer equal to 0, 1 or 2; BF.sub.3M, in which M=K or Na; B(OR.sup.11).sub.2, in which the two R.sup.11 radicals, which are identical or different, represent a hydrogen atom, an alkyl radical or form a carbon-based ring with the two oxygen atoms to which they are bonded; OR.sup.12, in which R.sup.12 represents a hydrogen atom or an alkyl, aryl or aralkyl radical; O(CO)R.sup.13, in which R.sup.13 represents a hydrogen atom or an alkyl, aryl or aralkyl radical; O(CO)OR.sup.14, in which R.sup.14 represents a hydrogen atom or an alkyl, aryl or aralkyl radical; N+R.sup.15R.sup.15R.sup.15A.sup., in which the R.sup.15, R.sup.15 and R.sup.15 radicals, which are identical or different, represent a hydrogen atom or an alkyl, aryl or aralkyl radical and A represents a chlorine or bromine atom; NR.sup.16(CO)R.sup.16, in which the R.sup.16 and R.sup.16 radicals, which are identical or different, represent a hydrogen atom or an alkyl or aryl radical or are connected together and form a ring, such as a pyrrolidone or caprolactam ring; NR.sup.17(CO)OR.sup.17, in which R.sup.17 and R.sup.17, which are identical or different, represent a hydrogen atom or an alkyl, aryl or aralkyl radical; CN; a halogen atom chosen from Cl, F and Br; NCS; OCH.sub.2-epoxy; COOR.sup.18, in which R.sup.18 represents a hydrogen atom or an alkyl, aryl or aralkyl radical; CONR.sup.19R.sup.19, in which R.sup.19 and R.sup.19, which are identical or different, represent a hydrogen atom or an alkyl or aryl radical; SO.sub.2R.sup.20, in which R.sup.20 represents an alkyl or aryl radical; azide (N.sub.3) and alkynyl; or (b) such that they together form a polymer chain P.sup.1; or (c) such that R.sup.5b is different from the other two groups R.sup.6 and R.sup.7, R.sup.6 and R.sup.7 have the same definitions as in the alternative (a), and R.sup.5b is a monoadduct radical of following formula: ##STR00030## in which R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.21, R.sup.22, R.sup.23, R.sup.24, Y and R.sup.25, have the same meanings as in the formula (IV) above, R.sup.6 and R.sup.7 have the same definitions as in the alternative (a), Z represents a divalent group chosen from a carbonyl group, a carbonate group, an alkylene group and an arylene group, and the sign # represents the point of attachment of the monoadduct radical to the CR.sup.6R.sup.7-monoadduct radical of the compound of formula (IV); then 2) a stage of thermolysis of the monoadduct of formula (IV) obtained above in the preceding stage in order to form a corresponding substituted thiolactone of formula (I).

2. Process according to claim 1, wherein R.sup.21, R.sup.22, R.sup.23 and R.sup.24 represent a hydrogen atom or an alkyl group.

3. Process according to claim 1, wherein R.sup.5 is a cyano group or a phthalimido group.

4. Process according to claim 1, wherein R.sup.25 is an alkyl group.

5. Process according to claim 1, wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 represent a hydrogen atom or an alkyl group.

6. Process according to claim 1, wherein said process results in the formation of a thiolactone of formula (I) chosen from: 3-(4-methyl-5-oxotetrahydrothiophen-2-yl)propanenitrile (TL1), and 2-(2-(4-methyl-5-oxotetrahydrothiophen-2-yl)ethyl)isoindoline-1,3-dione (TL2).

7. Process according to claim 1, wherein stage 1) of preparation of the monoadduct of formula (IV) is carried out without solvent, in water or in an organic solvent.

8. Process according to claim 1, wherein wherein the radical initiator used during stage 1) is chosen from organic peroxides, azo derivatives and redox systems.

9. Process according to claim 1, wherein stage 1) is carried out at a temperature varying from 10 to 140 C.

10. Process according to claim 1, wherein the thermolysis stage 2) is carried out without solvent.

11. Process according to claim 1, wherein the temperature of the thermolysis stage 2) is between 40 and 210 C.

12. Process according to claim 1, wherein the thermolysis stage 2) is carried out in a closed container and under vacuum.

13. Substituted thiolactones obtained according to a process as defined in claim 1 and corresponding to the following formula (I): ##STR00031## in which: R.sup.1, R.sup.2, R.sup.3 and R.sup.4, which are identical or different, represent a hydrogen atom or a group chosen from alkyl, acyl, aryl, heteroaryl, saturated or unsaturated cycloalkyl and saturated or unsaturated heterocycloalkyl groups, it also being possible for the R.sup.1, R.sup.2, R.sup.3 and R.sup.4 radicals to together form a saturated or unsaturated cycloalkyl or heterocycloalkyl group or an aryl or heteroaryl group; and R.sup.5, R.sup.6 and R.sup.7 are defined according to one of the following two options (i) or (ii): (i) R.sup.5 is chosen from a cyano group and a phthalimido group; and R.sup.6 and R.sup.7, which are identical or different, are chosen from a hydrogen atom, an alkyl group, an acyl group, an aryl group, a heteroaryl group, an aralkyl group, a saturated or unsaturated cycloalkyl group and a saturated or unsaturated heterocycloalkyl group, it being possible for said alkyl, acyl, aryl, heteroaryl, aralkyl, saturated or unsaturated cycloalkyl and saturated or unsaturated heterocycloalkyl groups to be substituted by an X group chosen from the following groups: P(O)(OR.sup.8)(OR.sup.8), in which the R.sup.8 and R.sup.8 radicals, which are identical or different, represent a hydrogen atom or an alkyl radical; C.sub.nF.sub.2n+1, in which n is an integer ranging from 1 to 20; SiR.sup.9.sub.p(OR.sup.10).sub.3-p, in which the R.sup.9 and R.sup.10 radicals, which are identical or different, represent a hydrogen atom or an alkyl radical and p is an integer equal to 0, 1 or 2; BF.sub.3M, in which M=K or Na; B(OR.sup.11).sub.2, in which the two R.sup.11 radicals, which are identical or different, represent a hydrogen atom, an alkyl radical or form a carbon-based ring with the two oxygen atoms to which they are bonded; OR.sup.12, in which R.sup.12 represents a hydrogen atom or an alkyl, aryl or aralkyl radical; O(CO)R.sup.13, in which R.sup.13 represents a hydrogen atom or an alkyl, aryl or aralkyl radical; O(CO)OR.sup.14, in which R.sup.14 represents a hydrogen atom or an alkyl, aryl or aralkyl radical; N+R.sup.15R.sup.15R.sup.15 A.sup., in which the R.sup.15, R.sup.15 and R.sup.15 radicals, which are identical or different, represent a hydrogen atom or an alkyl, aryl or aralkyl radical and A represents a chlorine or bromine atom; NR.sup.16(CO)R.sup.16, in which the R.sup.16 and R.sup.16 radicals, which are identical or different, represent a hydrogen atom or an alkyl or aryl radical or are connected together and form a ring, such as a pyrrolidone or caprolactam ring; NR.sup.17(CO)OR.sup.17, in which R.sup.17 and R.sup.17, which are identical or different, represent a hydrogen atom or an alkyl, aryl or aralkyl radical; CN; a halogen atom chosen from Cl, F and Br; NCS; OCH.sub.2-epoxy; COOR.sup.18, in which R.sup.18 represents a hydrogen atom or an alkyl, aryl or aralkyl radical; CONR.sup.19R.sup.19, in which R.sup.19 and R.sup.19, which are identical or different, represent a hydrogen atom or an alkyl or aryl radical; SO.sub.2R.sup.20, in which R.sup.20 represents an alkyl or aryl radical; azide (N.sub.3) and alkynyl; or (ii) R.sup.5, R.sup.6 and R.sup.7 are such that they together form a polymer chain P.sup.1.

14. Thiolactones according to claim 13, wherein they are chosen from: 3-(4-methyl-5-oxotetrahydrothiophen-2-yl)propanenitrile (TL1), and 2-(2-(4-methyl-5-oxotetrahydrothiophen-2-yl)ethyl)isoindoline-1,3-dione (TL2).

15. Polymers or functionalized particles, of flat surfaces or of polymers, comprising at least one substituted thiolactone of formula (I) as defined in claim 13.

Description

EXAMPLES

Example 1: Synthesis of 3-(4-methyl-5-oxotetrahydrothiophen-2-yl)propanenitrile (TL1) According to the Process in Accordance with the Invention

[0145] In this example, the thiolactone of following formula (TL1) was prepared:

##STR00017##

1) First Stage: Preparation of S-(cyanomethyl)-O-(3-methylbutan-2-yl) carbonodithioate (Xanthate of Formula (II); (XA1))

[0146] ##STR00018##

1.1) Substage 1: Preparation of Potassium O-1,2-Dimethyl Propyl) Xanthatate (XA0)

[0147] ##STR00019##

[0148] 100 g (1.13 mol) of 3-methylbutan-2-ol (Alfa Aesar), 63.65 g of potassium hydroxide (KOH, Sigma-Aldrich) and 90.7 g (1.19 mol) of carbon disulfide (CS.sub.2, Sigma-Aldrich) were suspended in 500 ml of tetrahydrofuran (THF, Sigma-Aldrich) at ambient temperature for 24 hours.

[0149] After complete dissolution of the KOH, the yellow emulsion was concentrated under reduced pressure, then triturated with pentane (Sigma-Aldrich) and finally filtered in order to obtain 185 g of the expected product XA0 in the form of a yellow solid (185 g, yield 80%).

[0150] .sup.1H NMR (300.13 MHz, D.sub.2O, 298K) : 5.31 (p, .sup.3J.sub.H,H=6.4 Hz, 1H, (CH.sub.3).sub.2CHCH(O)CH.sub.3); 2.07-1.84 (m, 1H, (CH.sub.3).sub.2CHCH(O)CH.sub.3); 1.27 (d, .sup.3J.sub.H,H=6.4 Hz, 3H, (CH.sub.3).sub.2CHCH(O)CH.sub.3); 0.96 (d, .sup.3J.sub.H,H=6.9 Hz, 6H, (CH.sub.3).sub.2CHCH(O)CH.sub.3) ppm.

[0151] .sup.13C{.sup.1H} NMR (75.47 MHz, D.sub.2O, 298K) : 232.6 (CS); 86.3 ((CH.sub.3).sub.2CHCH(O)CH.sub.3); 32.8 ((CH.sub.3).sub.2CHCH(O)CH.sub.3); 17.7 ((CH.sub.3).sub.2CHCH(O)CH.sub.3); 17.6 ((CH.sub.3).sub.2CHCH(O)CH.sub.3); 15.8 ((CH.sub.3).sub.2CHCH(O)CH.sub.3) ppm.

1.2) Substage 2: Preparation of S-(cyanomethyl)-O-(3-methylbutan-2-yl) Carbonodithioate (XA1)

[0152] 0.025 mol (5.05 g) of 2-bromoacetonitrile (Sigma-Aldrich) was added to a solution of 3.11 g (0.026 mol) of the compound XA0 obtained above in the preceding stage 1.1) in 25 ml of THF (Sigma-Aldrich), in an ice bath (highly exothermic reaction). Once the addition was complete, the reaction medium was stirred at ambient temperature for 16 hours and then filtered. The filtrate was concentrated under vacuum and the crude reaction product was purified by silica chromatography (eluent petroleum ether/ethyl acetate: 80:20, v:v) in order to recover the xanthate XA1 in the form of a yellow oil (3.58 g, yield 71%).

2) Second Stage: Preparation of Methyl 6-cyano-2-methyl-4-((((3-methylbutan-2-yl)oxy)carbonothioyl)thio)hexanoate (Monoadduct of Formula (IV); XA1CN)

[0153] ##STR00020##

2.1) Substage 1: Preparation of methyl 2-methyl-4-pentenoate (A1)

[0154] 0.075 mol (10.6 g) of ethyl 2-methyl-4-pentenoate (Sigma-Aldrich), 120 ml of methanol (Sigma-Aldrich) and 0.0038 mol (0.369 g) of 97% sulfuric acid (Sigma-Aldrich) were brought to reflux for 24 hours. The reaction mixture was subsequently cooled, diluted with 100 ml of diethyl ether (Sigma-Aldrich) and extracted with aqueous sodium chloride solution until a neutral pH was reached. The organic phase was dried over magnesium sulfate (Sigma-Aldrich) and evaporated under vacuum. Methyl 2-methyl-4-pentenoate (A1) was obtained in the form of a colourless liquid (7.15 g, yield 75%).

2.2) Substage 2: Preparation of methyl 6-cyano-2-methyl-4-((((3-methylbutan-2-yl)oxy)carbonothioyl)thio)hexanoate (XA1CN)

[0155] 3.45 g (0.17 mmol) of the xanthate XA1 obtained above in the preceding substage 1.2), 2.01 g (0.016 mmol) of methyl 2-methyl-4-pentenoate A1 obtained above in the preceding substage 2.1), 0.90 g (0.0023 mmol) of dilauroyl peroxide (LPO: radical initiator) and 3.5 ml of toluene were mixed in a Schlenk tube. The mixture was subsequently degassed by 3 operations of freezing under vacuum. After heating for 16 hours at a temperature of 90 C., the crude reaction product was purified by silica chromatography (eluent ethyl acetate/hexane (2:8, v:v)) in order to recover the monoadduct XA1CN (3.96 g, yield 79%, yellow oil).

[0156] .sup.1H NMR (300.13 MHz, CDCl.sub.3, 298K) (ppm): 5.59-5.47 (m, 1H, (CH.sub.3).sub.2CHCH(O)CH.sub.3), 3.94-3.74 (m, 1H, SCH(CO)CH), 3.67-3.66 (m, 3H, C(O)CH.sub.3), 2.76-2.60 (m, 1H, SCH.sub.2CH(CH.sub.3)), 2.54-2.45 (m, 2H, SCH.sub.2CH.sub.2CN), 2.19-1.93 (m, 4H, SCH(CH.sub.2CH.sub.2CN)CH.sub.2CH(CH.sub.3)), 1.78-1.52 (m, 1H, (CH.sub.3).sub.2CHCH(O)CH.sub.3), 1.31-1.27 (m, 3H, CH(O)CH.sub.3), 1.20-1.18 (d, 3H, SCH.sub.2CH(CH.sub.3)), 0.95-0.94 (m, 6H, (CH.sub.3).sub.2CHCH(O)CH.sub.3).

[0157] .sup.13C{.sup.1H} NMR (75.47 MHz, CDCl.sub.3, 298K) (ppm): 212.40 (CS), 176.12 (CO.sub.2CH.sub.3), 119.10 (CN), 86.47 ((CH.sub.3).sub.2CHCH(O)CH.sub.3), 51.94 (CO.sub.2CH.sub.3), 48.35-47.56 (SCHCH.sub.2CH.sub.2N), 37.72 (SCHCH.sub.2CH.sub.2CN), 37.06 (SCHCH.sub.2CH(CH.sub.3)), 32.70 ((CH.sub.3).sub.2CHCH(O)CH.sub.3), 31.62-30.90 (SCH(CH.sub.2CH(CH.sub.3)), 18.28-15.75 ((CH.sub.3).sub.2CHCH(O)CH.sub.3) and SCHCH.sub.2CH(CH.sub.3)), 14.78 (SCH.sub.2CH.sub.2CN).

[0158] IR: 2971, 2876, 2247, 1734, 1460, 1237, 1044 cm.sup.1.

[0159] Molar mass: CI (CH.sub.4), MH.sup.+:

[0160] Found: 332.1369 g/mol,

[0161] Calculated: 332.1354 g/mol.

3) Third Stage: Preparation of 3-(4-methyl-5-oxotetrahydrothiophen-2-yl)propanenitrile (Thiolactone of Formula (I); TL1)

[0162] 2.05 g (0.0062 mol) of XA1CN obtained above in the preceding substage 2.2) were placed in a Schlenk tube closed under vacuum and were brought to a temperature of 190 C. for 24 hours. The reaction mixture was subsequently cooled to ambient temperature and the volatile compounds formed were removed under vacuum. The thiolactone TL1 thus obtained in the form of a colourless oil was subsequently purified on a silica chromatography column (eluent hexane/ethyl acetate: 6:4 (v:v)) (0.42 g, yield 40%).

[0163] .sup.1H NMR (300.13 MHz, CDCl.sub.3, 298K) (ppm): 3.87-3.73 (m, 1H, CH(CH.sub.2).sub.2CN), 3.69-1.39 (m, 7H, C(O)CH(CH.sub.3)CH.sub.2CH(CH.sub.2).sub.2), 1.10-1.07 (m, 3H, CHCH.sub.3).

[0164] .sup.13C{.sup.1H} NMR (75.47 MHz, CDCl.sub.3, 298K) (ppm): 209.06-207.98 (CO), 118.76 (CN), 48.69 (CHCH.sub.3), 45.46-44.88 (CH(CH.sub.2).sub.2CN), 40.30-38.74 (CH(CH.sub.3)CH.sub.2CH), 32.09-31.67 (CH(CH.sub.2CH.sub.2CN), 16.10-15.06 (CH(CH.sub.2CH.sub.2CN), 15.12-14.34 (CHCH.sub.3).

[0165] IR: 2970, 2875, 2247, 1701, 1453, 756 cm.sup.1.

[0166] Molar mass: CI (CH.sub.4), MH.sup.+:

[0167] Found: 170.0643 g/mol,

[0168] Calculated: 170.0640 g/mol.

Example 2: Synthesis of 2-(2-(4-methyl-5-oxotetrahydrothiophen-2-yl)ethyl)isoindoline-1,3-dione (TL2) According to the Process in Accordance with the Invention

[0169] In this example, the thiolactone of following formula (TL2) was prepared:

##STR00021##

1) First Stage: Preparation of S-((1,3-dioxoisoindolin-2-yl)methyl)O-(3-methylbutan-2-yl) Carbonodithioate (Xanthate of Formula (II); (XA2))

[0170] ##STR00022##

[0171] 0.021 mol (4.99 g) of 2-(bromomethyl)-1H-isoindole-1,3(2H)-dione (Sigma-Aldrich) was added to a solution of 4.04 g (0.020 mol) of the compound XA0 obtained in substage 1.1) of Example 1 in 35 ml of acetone (Sigma-Aldrich), in an ice bath (highly exothermic reaction). Once the addition was complete, the reaction medium was stirred at ambient temperature for 3 hours and then filtered. The filtrate was concentrated under vacuum in order to obtain the expected product XA2 in the form of a yellow oil (5.84 g, yield 91%) which will be used in the following stage without purification.

2) Second Stage: Preparation of methyl 6-(1,3-dioxoisoindolin-2-yl)-2-methyl-4-((((3-methylbutan-2-yl)oxy)carbonothioyl)thio)hexanoate (Monoadduct of Formula (IV); XA2PH)

[0172] ##STR00023##

[0173] 3.82 g (0.012 mol) of the xanthate XA2 obtained above in the preceding stage 1), 1.38 g (0.012 mol) of methyl 2-methyl-4-pentenoate A1 obtained above in stage 2.1) of Example 1 and 0.64 g (0.0016 mol) of dilauroyl peroxide (LPO: radical initiator) were mixed in a Schlenk tube. The mixture was subsequently degassed by 3 operations of freezing under vacuum. After heating for 16 hours at a temperature of 90 C., the crude reaction product was purified by silica chromatography (eluent ethyl acetate/hexane (2:8, v:v)) in order to recover the unreacted xanthate XA2, on the one hand, and the monoadduct XA2PH, on the other hand (1.9 g, yield 91%, yellow oil).

[0174] .sup.1H NMR (300.13 MHz, CDCl.sub.3, 298K) (ppm): 7.86-7.67 (m, 4H, H.sub.ar), 5.56-5.40 (m, 1H, (CH.sub.3).sub.2CHCH(O)CH.sub.3), 5.22-4.07 (m, 1H, SCH(CO)CH), 3.86-3.70 (m, 3H, SCHCH.sub.2CH.sub.2N), 3.67-3.62 (m, 3H, C(O)CH.sub.3), 2.80-2.60 (m, 1H, SCHCH.sub.2CH(CH.sub.3)), 2.26-1.26 (m, 5H, SCH(CH.sub.2CH.sub.2N)CH.sub.2CH(CH.sub.3)), 1.29-1.15 (m, 6H, CH(O)CH.sub.3 and SCH.sub.2CH(CH.sub.3)), 0.92-0.86 (m, 6H, (CH.sub.3).sub.2CHCH(O)CH.sub.3).

[0175] .sup.13C{.sup.1H} NMR (75.47 MHz, CDCl.sub.3, 298K) (ppm): 213.17 (CS), 176.41 (CO.sub.2CH.sub.3), 168.22 (C(O)NC(O), 133.90-123.24 (C.sub.ar), 85.75 ((CH.sub.3).sub.2CHCH(O)CH.sub.3), 51.77 (CO.sub.2CH.sub.3), 46.87-46.17 (SCHCH.sub.2CH.sub.2N), 37.18 (SCHCH.sub.2CH(CH.sub.3)), 37.91-33.56 (SCH(CH.sub.2).sub.2N)CH.sub.2CH(CH.sub.3)), 32.69 ((CH.sub.3).sub.2CHCH(O)CH.sub.3), 18.26-15.77 ((CH.sub.3).sub.2CHCH(O)CH.sub.3) and SCHCH.sub.2CH(CH.sub.3)).

[0176] IR: 2970, 1773, 1714, 1398, 1234, 1046, 721 cm.sup.1.

[0177] Molar mass: CI (CH.sub.4), MH.sup.+:

[0178] Found: 452.1572 g/mol,

[0179] Calculated: 452.1565 g/mol.

3) Third Stage: Preparation of 2-(2-(4-methyl-5-oxotetrahydrothiophen-2-yl)ethyl)isoindoline-1,3-dione (Thiolactone of Formula (I); TL2)

[0180] 1.67 g (0.0037 mol) of XA2PH obtained above in the preceding stage 2) were placed in a Schlenk tube closed under vacuum and were brought to a temperature of 190 C. for 24 hours. The reaction mixture was subsequently dissolved in 3 ml of ethyl acetate and then precipitated from 200 ml of hexane. The white solid obtained was filtered on a Bichner funnel. The thiolactone TL2 was thus obtained in the form of a white solid (0.310 g, yield 30%).

[0181] .sup.1H NMR (300.13 MHz, CDCl.sub.3, 298K) (ppm): 7.77-7.64 (m, 4H, H.sub.ar), 3.80-3.61 (m, 3H, CH(CH.sub.2CH.sub.2N), 2.68-1.40 (m, 5H, C(O)CH(CH.sub.3)CH.sub.2CH(CH.sub.2CH.sub.2N), 1.11-1.06 (m, 3H, CHCH.sub.3).

[0182] .sup.13C{.sup.1H} NMR (75.47 MHz, CDCl.sub.3, 298K) (ppm): 210.0-209.0 (C(O)S), 168.19 (N(C(O)CH).sub.2), 134.17-123.33 (C.sub.ar), 48.33 (CH(CH.sub.3)), 45.00-44.56 (CH.sub.2CH(CH.sub.2CH.sub.2N)), 40.87-39.15 (CH.sub.2CH(CH.sub.2CH.sub.2N)), 36.47-35.40 (CH.sub.2CH(CH.sub.2CH.sub.2N)), 15.20-14.38 (CH(CH.sub.3)).

[0183] IR: 2936, 1705, 1699, 1399, 1370, 724 cm.sup.1.

[0184] Molar mass: CI (CH.sub.4), MH.sup.+:

[0185] Found: 289.0782 g/mol, Calculated: 289.0773 g/mol.