WO2018177989A1

WO2018177989A1 - New dithiospiroketal compounds and use thereof

Info

Publication number: WO2018177989A1
Application number: PCT/EP2018/057605
Authority: WO
Inventors: Samir Zard; Béatrice SIRE
Original assignee: Ecole Polytechnique; Centre National De La Recherche Scientifique
Priority date: 2017-03-28
Filing date: 2018-03-26
Publication date: 2018-10-04
Also published as: FR3064633B1; FR3064633A1

Abstract

The present invention relates to compounds of formula (I) and the preparation methods thereof. It also relates to the use of compounds of formula (I) as monomeric compounds and polymers derived from the homopolymerisation or copolymerisation of at least one compound of formula (I).

Description

NOVEL DITHIOSPIROCETALS COMPOUNDS

AND THEIR USE

The present invention relates to novel compounds particularly useful for the development of new polymers.

Today, polymers are materials considered in a wide variety of industrial fields such as transport, eg automotive, furniture and household appliances, packaging, coatings, building and public works, sports and leisure, medical, or electricity and electronics.

The properties of the polymers, whether thermoplastic, thermosetting or elastomeric, are advantageously adjustable through the choice of monomers considered for their preparation.

For obvious reasons, manufacturers are continually in a dynamic approach to access new polymeric materials and / or cheaper polymer synthesis routes and easier implementation.

Indeed, some monomers do not lend themselves to immediate polymerization and may require preliminary functionalizations, sometimes laborious and expensive, to give them a required compatibility, obtaining the desired polymer.

Moreover, it is sought today to favor natural resources for the synthesis of the corresponding monomers and polymers.

Indeed, with a declining supply of oil, the discovery of alternative solutions to produce chemicals is increasingly important. About 96% of the organic compounds currently used are derived from non-renewable fossil fuels.

However, biomass represents today a potential input as a raw material for forming monomeric entities, provided that it has an easy and inexpensive synthetic route to enhance it.

The inventors have now discovered that it is possible to respond effectively to the aforementioned expectations subject to considering new monomeric entities.

Thus, the present invention relates, according to a first aspect, to compounds of formula (I):

wherein :

- W and Y, identical or different, represent a non-reactive functional group with respect to a thiocarbonylthio function;

R ₁ and R ₂ , which may be identical or different, represent a C ₁ -C 5 alkyl chain optionally interrupted by one or more oxygen, nitrogen, sulfur and / or silicon atoms, and / or by one or more groups selected from optionally substituted cycloalkyl, aryl or heteroaryl;

R ₃ and R ₄ , which may be identical or different, represent a hydrogen atom or a C 1 -C 6 -alkyl optionally substituted with a non-reactive functional group with respect to a thiocarbonylthio function; or R 3 and R ₄ together form a cycloalkyl or heterocycloalkyl, optionally substituted by a carbonyl function;

R 5 and R 5, which may be identical or different, represent a hydrogen atom or an optionally substituted C 1 -C 15 -alkyl, or R 5 and 5 together form a cycloalkyl or a heterocycloalkyl, optionally substituted with a carbonyl function;

n and n ', which are identical or different, are equal to 0, 1 or 2;

said compounds of formula (I) may be in all isomeric forms, in particular racemic, enantiomeric and diastereoisomeric.

According to another of its aspects, the present invention relates to the use of these compounds as monomeric compounds.

The present invention also relates to polymers derived from homopolymerization or copolymerization of at least one compound of formula (I) as described above.

The compounds according to the invention prove to be advantageous in several ways.

First of all, unlike the compounds currently used for the preparation of polymer, their synthesis is easy and does not require a very large number of steps. They have the advantage of being able to be prepared from biomass raw materials, and thus be consistent with the principles of sustainable chemistry.

In addition, as is apparent from the examples below, the compounds according to the invention make it possible to prepare a wide variety of polymers, depending on the desired application.

The polymers synthesized from the compounds according to the invention have excellent mechanical and thermal properties, and very good chemical stability.

In addition, the variety of possible substitutions at the level of the monomeric compound of formula (I) allows a great modulation of the structure and consequently of its properties. The polymers may in particular be prepared from one or more compounds of formula (I).

The inventors have also discovered that the bicyclic unit comprising the sulfur atoms in the formula (I) makes it possible to obtain very good properties in terms of the rigidity of the polymers. Other features, variants and advantages of the invention will emerge more clearly on reading the description and the examples which follow, given by way of illustration and not limitation of the invention.

In the rest of the text, the expressions "between ... and ...", "ranging from ... to ..." and "varying from ... to ...", are equivalent and mean to mean that the terminals are included unless otherwise stated.

Unless otherwise indicated, the expression "comprising / including a" shall be understood as "comprising / including at least one".

DEFINITIONS

In the context of the present invention:

- a functional group denotes any chemical group belonging to a class of organic compounds characterized by chemical properties. As an example of a functional group, mention may be made of: amides, acyls, alkoxy, nitriles, aryls, heteroaryls, alkenyls, carbonyls, thiocarbonyls, carboxyls, thiocarboxyls, carbamyls, thiocarbamyls; thiocarbamides, alcohols, thiols, or substituted or unsubstituted amines; In particular, a hydrogen atom is not a functional group within the meaning of the invention.

a non-reactive group with respect to a thiocarbonylthio function denotes any group that does not react chemically with a thiocarbonylthio function;

a polymerizable group designates a group capable of bonding to form a polymer,

a group or a substituted radical denotes a group or a radical modified by addition of a functional group as defined above;

an isomeric form denotes racemates, enantiomers, diastereoismers, epimers, tautomers as well as conformational isomers;

a racemic form denotes a mixture of two enantiomers in a ratio of 55:45 to 45:55;

- a monomeric entity or compound means an entity or a compound that can assemble to form a polymer;

a leaving group denotes a chemical group which can be easily detached from the rest of the compound, in particular by substitution. As a leaving group, mention may be made of halogens, such as chlorine, bromine or iodine, a sulphonate group such as a mesylate, a triflate or a tosylate;

"Ct-Cz" denotes a carbon chain that can have from t to z carbon atoms, where t and z can take, for example, the values from 1 to 25; for example C1-C3 is a carbon chain which may have from 1 to 3 carbon atoms;

an alkyl denotes a linear or branched monovalent saturated aliphatic group, which may for example comprise from 1 to 25 carbon atoms. By way of examples, mention may be made of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl and the like. ;

an alkyl chain denotes a linear or branched saturated divalent alkyl group which may for example comprise from 1 to 25 carbon atoms;

an aryl or an aromatic ring designates a mono-, bi- or tricyclic aromatic group comprising, for example, between 6 and 14 carbon atoms. Examples of aryl groups or aromatic rings include phenyl, naphthyl and the like. ;

a heteroaryl or a heteroaromatic ring denotes a 5- to 14-membered mono-, bi- or tricyclic aromatic heterocyclic group containing from 1 to 8 heteroatoms selected for example from oxygen, sulfur and nitrogen. As examples of heteroaryl groups or heteroaromatic rings, there may be mentioned pyridine, pyrazine, pyrimidine, pyrazole, oxadiazole, thiazole, imidazole, benzothiophene, quinoline, indole, etc. groups. ;

cycloalkyl means a non-aromatic, unsaturated, saturated or partially unsaturated mono- or cyclocyclic group of 3 to 7 members. By way of examples, mention may be made of cyclopropyl, cyclopropene, cyclobutyl, cyclobutene, cyclopentyl, cyclopentene, cyclohexyl, and the like.

heterocycloalkyl denotes a non-aromatic, unsaturated, saturated or partially unsaturated mono- or cyclocyclic group comprising from 3 to 7 members, comprising one or more heteroatoms chosen, for example, from oxygen, sulfur and nitrogen. By way of examples, there may be mentioned azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl, homopiperazinyl, dihydro-oxazolyl, dihydro-thiazolyl, dihydro-imidazolyl, dihydro-pyrrolyl or tetrahydropyridinyl, etc. groups.

an alkoxy denotes an -O-alkyl radical in which the alkyl group is as previously defined;

an alkylthio denotes a radical -S-alkyl where the alkyl group is as previously defined;

an aryloxy denotes a radical -O-aryl where the aryl group is as previously defined;

an arylthio denotes a -S-aryl radical in which the aryl group is as previously defined;

a thiocarbonylthio function denotes a function -S-C (= S) -;

a carbonyl function denotes a group comprising a -C (= O) function. By way of example, mention may be made of ketones, esters, carbamates, amides, ureas, etc. ;

an alkali metal designates an alkali metal of column 1 of the periodic table of the elements, with the exception of hydrogen. As an alkali metal, mention may be made of lithium, sodium, potassium, rubidium, cesium or francium;

- an alkaline earth or alkaline metal earthy refers to six chemical elements of the ^2nd group of the periodic table of elements. As alkaline earth, mention may be made of beryllium, magnesium, calcium, strontium, barium or radium. COMPOUNDS ACCORDING TO THE INVENTION

As mentioned above, the present invention relates to compounds of formula (I):

wherein :

-W and Y, identical or different, represent a non-reactive functional group with respect to a thiocarbonylthio function;

n and n ', which are identical or different, are equal to 0, 1 or 2;

said compound of formula (I) may be in all isomeric forms, in particular racemic, enantiomeric and diastereoisomeric.

Preferably, W and Y are polymerizable functional groups. Preferably, in the compounds according to the invention, W and Y, which are identical or different, represent a functional group chosen from -OR, -COOR, -C (= O) R, -CO-O-CO-R, -CO -O-NRR ', -O-COOR, -NRR', -CN, -CR = NR ', -CO-NRR', -CO-NR-OR ',

-NR-COOR ', -NR-CO-NR'R ", -N = C = O, -SR or -S (= O) R, -S (= O) ₂ R, -S (= O) ₂ OR-, S (= O) ₂ NRR ', -P (= O) (OR) ₂ , -P (= O) (OR) (NR'R "), -P (= O) (NRR') ₂ with R, R 'and R ", identical or different, representing a hydrogen atom, a C 1 -C 12 -alkyl, or a cycloalkyl, an aryl or a heteroaryl.

More preferably, W and Y, which may be identical or different, represent a functional group chosen from -OR, -COOR, -NR-COOR 'or -NRR', with R and R ', which may be identical or different, representing a hydrogen atom or a C 1 -C 12 -alkyl.

According to a preferred embodiment, in the compounds according to the invention, R 1 and R ₂ , which are identical or different, represent a C 1 -C 18 alkyl chain, and preferably a C 1 -C 10 alkyl chain.

Preferably, in the compounds according to the invention, R ₃ and R ₄ represent a hydrogen atom.

Preferably, in the compounds according to the invention, R ₅ and 5 represent a hydrogen atom.

According to a preferred embodiment, in the compounds according to the invention, n and n 'are identical, and in particular are equal to 0 or 2.

Preferably, in the compounds according to the invention, W and Y are identical, and R 1 and R ₂ are identical.

According to a particularly preferred embodiment, the compounds of formula (I) are chosen from:

Preferably, in the compounds according to the invention, W and Y are different. According to a particularly preferred embodiment, the compounds of formula (I) are chosen from:

The present invention also relates to the compounds of formula (I) for which the definitions of W, Y, R 1, R ₂ , R ₃ , R 4, R 5, R 6 and / or n as defined above are combined with one another. METHODS OF PREPARATION

According to one of its aspects, the present invention also relates to a process for preparing a compound as defined above, in which W and Y are identical, and Ri and R ₂ are identical, comprising at least the following steps:

A) bringing into contact a compound of formula (1) below:

in which :

R ₃ and R ₄ , which may be identical or different, represent a hydrogen atom or a C 1 -C 6 -alkyl optionally substituted with a non-reactive functional group with respect to a thiocarbonylthio function; or R ₃ and R ₄ together form a cycloalkyl or a heterocycloalkyl optionally substituted with a carbonyl function; and

Z represents an optionally substituted C 1 -C 10 -alkyl, an optionally substituted cycloalkyl, an aryl, a heteroaryl, an optionally substituted C 1 -C 10 -alkoxy, an optionally substituted aryloxy, an optionally substituted C 1 -C 10 -alkylthio, an optionally substituted arylthio , or a radical NRR 'with R and R', which may be identical or different, representing an optionally substituted C 1 -C 10 -alkyl, an optionally substituted cycloalkyl, an aryl or a heteroaryl, and preferably Z represents a C 1 -C 10 -alkoxy or a optionally substituted aryloxy radical; with at least two equivalents of a compound (2) of the following formula:

in which :

-W represents a non-reactive functional group with respect to a thiocarbonylthio function;

-R represents a _{Ci-C2-5-alkyl} chain optionally interrupted by one or more oxygen, nitrogen, sulfur and / or silicon, and / or by one or more aryl or heteroaryl optionally substituted; and -R ₅ and Re, which may be identical or different, represent a hydrogen atom or an optionally substituted C 1 -C 15 -alkyl, or R 5 and 5 together form a cycloalkyl or a heterocycloalkyl, optionally substituted with a carbonyl function, preferably R 5 and 5 represent a hydrogen atom; in the presence of a physicochemical initiator, and optionally a solvent, under conditions conducive to the formation of a compound of formula (3) below:

^Z 0)

wherein W, Z, R 1, R 3, R ₄ , R 5 and 5 are as defined above;

B) i) heating the reaction medium comprising said compound (3) or bringing said compound (3) into contact with a base, in particular chosen from sodium hydroxide, lithium hydroxide (LiOH), potassium hydroxide, an alcoholate, aqueous ammonia or an amine, preferably selected from ethylene diamine or pyrrolidine, and ii) contacting the reaction medium comprising said compound (3) with an organic or inorganic acid, the steps i) and ii) being carried out simultaneously or successively, preferably successively in the order i) then ii); under conditions conducive to the cyclization of said compound (3) to form the compound (4) of the following formula:

wherein W, R 1, R 3, R ₄ , R 5 and 5 are as defined above; and

C) Optionally, bringing said compound (4) into contact with an oxidant, in particular a peracid, under conditions that are effective for the formation of the compound (5) of the following formula:

wherein W, R 1, R ₃ , R ₄ , R 5 and 5 are as defined above; and n and n 'are the same or different and equal to 1 or 2.

In a particular embodiment, the process further comprises a step of hydrolyzing the compound of formula (4) or (5).

According to a particular mode, the method may further comprise a step of isolating the compound (3) at the end of step A).

According to another of its aspects, the present invention also relates to a process for preparing a compound as defined above, in which W and Y are different, comprising at least the following steps:

A ') bringing into contact a compound of formula (6) below:

in which :

R ₃ and R ₄ , which may be identical or different, represent a hydrogen atom or a C 1 -C 6 -alkyl optionally substituted with a non-reactive functional group with respect to a thiocarbonylthio function; or R 3 and R ₄ together form a cycloalkyl or a heterocycloalkyl optionally substituted by a carbonyl function;

Z represents an optionally substituted C 1 -C 10 -alkyl, an optionally substituted cycloalkyl, an aryl, a heteroaryl, an optionally substituted C 1 -C 10 -alkoxy, an optionally substituted aryloxy, an optionally substituted C 1 -C 10 -alkylthio, an optionally substituted arylthio , or a radical NRR 'with R and R', identical or different, representing an optionally substituted C 1 -C 10 -alkyl, a optionally substituted cycloalkyl, aryl or heteroaryl, and preferably Z represents a C 1 -C 10 -alkoxy or an optionally substituted aryloxy radical; and

-G represents a leaving group, in particular chosen from a chlorine or a bromine, and preferably a chlorine;

with at least one equivalent of a compound (7) of the following formula:

in which :

-W represents a non-reactive functional group with respect to a thiocarbonylthio function; -Ri represents a C1-C25-alkyl chain optionally interrupted by one or more oxygen, nitrogen, sulfur and / or silicon atoms, and / or by one or more optionally substituted aryl or heteroaryl; and

-R ₅ and Re, which may be identical or different, represent a hydrogen atom or an optionally substituted C 1 -C 15 -alkyl, or R ₅ and R ₅ together form a cycloalkyl or a heterocycloalkyl, optionally substituted by a carbonyl function, preferably R ₅ and Re represent a hydrogen atom; in the presence of a physicochemical initiator, and optionally a solvent, under conditions conducive to the formation of a compound of formula (8) below:

^Z (8)

wherein W, Z, G, R 1, R ₃ , R ₄ , R _{5 and} R ₆ are as defined above;

B ') bringing into contact said compound of formula (8) obtained at the end of step A') with a salt of the thiocarbonylthio compound of formula ZC (= S) MS, in which Z is as defined above and M represents an alkali metal, an alkaline earth metal or an ammonium, and preferably sodium or potassium, under conditions conducive to the formation of a compound of formula (9) below:

(9) wherein W, Z, R 1, R ₃ , R ₄ , R _{5 and} R ₆ are as defined above;

C) bringing into contact said compound of formula (9) obtained at the end of step B ') with at least one equivalent of a compound (10) of following formula:

R-Y

R_ R _*

(10) wherein:

Y is different from W in the formula (9) as defined above and represents a non-reactive functional group with respect to a thiocarbonylthio function;

R ₂ represents a C ₁ -C 25 alkyl chain optionally interrupted by one or more oxygen, nitrogen, sulfur and / or silicon atoms, and / or by one or more optionally substituted aryl or heteroaryl groups; and -R ₅ and Re, identical or different, represent a hydrogen atom, or a

C 1 -C 15 -alkyl optionally substituted, or R ₅ and R ₉ together form cycloalkyl or heterocycloalkyl, optionally substituted with a carbonyl function, preferably R ₅ and R ₆ represent a hydrogen atom; in the presence of a physicochemical initiator, and optionally a solvent, under conditions conducive to the formation of a compound of formula (1 1) below:

wherein W, Y, R 1, R ₂ , R ₃ , R 4, R 5, R 6 and Z are as defined above;

D ') i) heating the reaction medium comprising said compound (3) or bringing said compound (3) into contact with a base, in particular chosen from soda, lithium hydroxide (LiOH), potassium hydroxide, an alkoxide, aqueous ammonia or an amine, preferably selected from ethylene diamine or pyrrolidine, and ii) contacting the reaction medium comprising said compound (3) with an organic or inorganic acid, the steps i) and ii) being carried out simultaneously or successively preferably successively in the order i) then ii); under conditions conducive to the cyclization of said compound (11) to form the compound (12) of the following formula:

wherein W, Y, R 1, R ₂ , R ₃ , R 4, R 5 and 5 are as defined above;

E ') Optionally, bringing said compound (12) into contact with an oxidant, in particular a peracid, under conditions that are effective for the formation of the compound (13) of the following formula:

wherein W, Y, R 1, R ₂ , R ₃ , R 4, R 5 and 5 are as defined above; and n and n 'are the same or different and equal to 1 or 2.

According to a particular embodiment, the method further comprises a step of isolating the compound (11) at the end of step C). Preferably, in the processes described above, the physicochemical initiator is chosen from peroxidic agents, agents that are sensitive to visible light or UV light, and preferably is a peroxide, in particular dilauroyl peroxide or peroxide. di-t-butyl.

According to one particular embodiment, in the processes according to the invention, step A) or A ') is carried out in a solvent medium.

In particular, the solvent is chosen from water, ethyl acetate, t-butyl alcohol, chlorobenzene, t-butyl methyl ether, acetic acid, 1,2-dichloroethane, or a alkane such as cyclohexane, heptane or octane.

Preferably, the solvent is chosen from water or ethyl acetate, and more preferably is ethyl acetate.

According to another particular embodiment, in the processes according to the invention, step A) or A ') is carried out without an accompanying solvent medium. For example, in this particular embodiment, the compound of formula (2), (7) or (10) can act as a solvent.

When steps B) i) or D ') i) of the processes described above implement a heating step, said heating is in particular carried out at a temperature of between 100 ° C. and 230 ° C., and preferably between 140 ° C and 180 ° C.

This embodiment is particularly advantageous on an industrial scale. Indeed, at this scale, the heating step can be coupled to the radical addition.

According to one particular embodiment, in the processes according to the invention, the base is chosen from soda, lithium hydroxide (LiOH), potassium hydroxide, an alcoholate, ammonia, or an amine, preferably chosen from ethylene diamine or pyrrolidine.

Preferably, the base is chosen from ethylene diamine and / or pyrrolidine.

According to a preferred embodiment, the base is ethylene diamine.

According to a preferred embodiment, the base is pyrrolidine. The use of pyrrolidine advantageously makes it possible to obtain the odorless research compound of sulfur byproducts. According to one particular embodiment, in the processes according to the invention, the organic or inorganic acid is, for example, chosen from among HCl, H 2 SO 4, H 3 PO 4, acetic acid, citric acid, KHSO 4 or even NaHSO ₄ .

According to one particular embodiment, in the processes according to the invention, the oxidant is, for example, chosen from a peracid, a perborate, hydrogen peroxide in the presence of an acid or of a catalyst, a periodate, a permanganate, a persulfate or oxone or even ozone.

Preferably, the oxidant is a peracid.

According to a preferred embodiment, the processes according to the invention comprise an oxidation step (step C) or E ')), successively to steps B) or D') to form the compound (5) or (13). In other words, the oxidation step is carried out before a possible polymerization of the compound (4) or (12). This embodiment is particularly advantageous when n and / or n 'are equal to 0 or 2.

According to another embodiment, the compound (4) or (12) is polymerized and the polymers then undergo an oxidation step. This embodiment is particularly advantageous when n and / or n 'are equal to 1.

POLYMERS

The present invention also relates to the use of a compound as defined above as a monomeric compound.

Thus, the present invention also relates to polymers derived from homopolymerization or copolymerization of at least one compound of formula (I) as defined above.

The term "copolymer" means a polymer resulting from the copolymerization of at least two different types of monomer, for example two different types of monomers of formula (I) or a monomer of formula (I) and a monomer (A) as defined below.

Preferably, the polymers according to the invention are of formula (II):

wherein :

-W and Y ', identical or different, derive from a functional group as defined above;

-A represents a monomeric entity distinct from a monomeric entity derived from a compound as defined above;

-p is 0 or 1;

R ₁ , R ₂ , R ₃ , R 4, R 5, R 6, n and n 'are as defined above.

According to a preferred embodiment, W and Y 'are chosen from -O-, -CO-O-, -C (= O) -, -CO-O-CO-, -CO-O-NR-, -O-CO -O-, -NR-, -CR = N-, -CO-NR-, -CO-NR-O-, -NR-CO-O-, -NR-CO-NR'-, -S- or S (= 0) -, -S (= 0) ₂ -, -S (= 0) ₂ 0-, -S (= O) ₂ NR-, -P (= 0) (OR) 0-, -P (= O) (OR) NR ', -P (= O) (NRR') NR'-, with R and R ', which may be identical or different, representing a hydrogen atom, a Ci-Ci ₂ -alkyl, or cycloalkyl, aryl or heteroaryl.

According to a particularly preferred embodiment, the polymers according to the invention are chosen from:



APPLICATIONS

The present invention also relates to the use of the compounds and polymers as described above.

For example, the compounds of formula (I) may be useful as surfactants.

As indicated above, the present invention also relates to the use of the compounds of formula (I) as a monomeric compound.

The polymers according to the invention may be thermoplastics, thermosets or elastomers.

The polymers can in particular be used in the standard fields well known to those skilled in the art, depending on the properties of the polymer obtained, in particular according to the mechanical and thermal properties.

The properties of the polymers can be easily modulated depending on the choice of substituents. For example, when n and n 'are 0, the dithiospiroketal unit will be nonpolar and hydrophobic and when n and n' are equal to 1 or 2, the dithiospiroketal unit will be polar and rather hydrophilic.

For example, the polymers according to the invention may be useful as raw materials for the manufacture of porous fibers, plasticizers for surface treatments, for coating paper, for water repellency of leather, as resins for adhesives, paints, stains, varnishes and anti-corrosion coatings for metals, as adjuvants and / or stabilizers for other polymers, emulsifiers and / or gelling agents for creams and coatings; detergents, etc.

The examples and figure presented below are only given by way of illustration and not limitation of the invention.

FIG. 1: thermogravimetric analysis (ATG) curve of the polymer prepared in Example 10.

EXAMPLES

EXAMPLE 1

Preparation of dimethyl 10,16-bis ((ethoxycarbonothioyl) thio) -13-oxopentacosanedioate according to method I or II

Method I:

A mixture of Ο, Ο'-diethyl S, S '- (2-oxopropane-1,3-diyl) dicarbonodithioate bisxanthate (2.4 g, 8.05 mmol) and methyl-10-undecenoate (4.7 mL) 20.8 mmol, 2.6 equivalents) in ethyl acetate (4 mL) is refluxed under nitrogen for 10 minutes.

Dilauroyl peroxide (DLP) (10 mol%, 0.320 g) is then added.

The reaction is monitored on thin layer chromatography (tlc) (petroleum ether / AcOEt: 8/2).

The solvent is then evaporated under reduced pressure and the resulting residue is purified on a silica gel column using a solvent gradient (petroleum ether / AcOEt: 10/0 to 85/15) to give 4.4 g (78%). %) of the di-addition product as a mixture of diastereoisomers.

NMR (400 MHz, CDCl ₃ ) δ 4.69-4.59 (qd, J = 7.2, 4H, 20C% CH ₃ ); 3.75- 3.68 (m, 2H, 2 CHS); 3.67 (s, 6Η, 20Me); 2.56 (t, J = 7.5 Hz, 4H, 2CH ₂ CO); 2.30 (t, J = 7.5 Hz, 4H, 2CH ₂ CO); 2.11-2.02 (m, 2H, 2CHHCHS); 1.85-1.75 (m, 2H, 2CHHCHS); 1.67-1.58 (m, 9H, CH ₂ , 4.5 CH ₂ ); 1.44-1.41 (m + t, J = 7.1 Hz, 9H, 1.5 CH ₂ , 20 CH ₂ CH ₃ ); 1.28 (bs, 16Η, 8CH ₂ ). ¹³ C NMR (101 MHz, CDCl ₃ ) δ 214.6 (2CS); 209.1 (CO); 174.3 (2C0 ₂ Me); 69.9 (20CH ₂ CH ₃ ); 51.5; 51.11; 51.09 (2CHS, 20Me); 39.9; 34.7; 34.1; 29.4; 29.3; 29.2; 29.1; 28.0; 26.8; 24.9 (20CH ₂ ); 13.8 (20CH ₂ CH ₃ ).

HRMS (M ⁺⁾ calculated for C ₃₃ H ₅ 807S4: 694.3065; found: 694,3072.

Method II:

A mixture of Ο, Ο'-diethyl 5 ', 5 ^, - (2-oxopropane-1,3-diyl) dicarbonodithioate bisxanthate (2.4 g, 8.05 mmol) and methyl-10-undecenoate (5.42 mL, 24.15 mmol, 3 equivalents) is placed in a closed tube and heated at 130-140 ° C for 10 minutes.

Di-tert-butyl peroxide (10 mol%, 0.15 mL) is then added.

After heating for 5 hours at 130-140 ° C., the excess of the reactants is evaporated under a stream of nitrogen at 120 ° C.

NMR shows that the tenanthate is obtained pure in the form of an oil with almost quantitative yield.

Preparation of dimethyl 9,9 '- (6-dithiaspiro [4,4] nonane-2,7-diyl) dinonanoate according to method Γ or ΙΓ

Method Γ:

To a degassed solution of dixanthate obtained above (3.2 g, 4.61 mmol) in ethanol (5 mL) is added at 0 ° C. ethylenediamine (1.23 mL, 4 equivalents).

The reaction mixture is stirred at 0 ° C until the total disappearance of the starting dixanthate (TLC: petroleum ether / diethyl ether: 6/4).

The mixture is then neutralized with a citric acid solution and extracted three times with petroleum ether to yield the dithiospiroketal (1.38 g) which is directly treated with KHSO ₄ (1 g) in cyclohexane (20 mL) at room temperature overnight to ensure complete cyclization.

Dithiospiroketal is isolated as diastereoisomers after filtration and evaporation of the solvent.

The solid (1.3 g) was recrystallized from methanol to give the desired product (1.2 g, 52% over two steps) as white crystals.

NMR (400 MHz, CDCl3) δ 3.67 (s, 6H, 20Me); 3.64 (m, 0.5H, 0.5 CHS); 3.56 (m, 0.5H, 0.5 CHS); 3.40 (m, 1H, CHS); 2.41-2.05 (m + t, 10H, 5 CH ₂ ); 1.85-1.43 (m, 10H, 5CH ₂ ); 1.27 (bs, 20H, 10CH ₂ ).

¹³ C NMR (101 MHz, CDCl3) δ 174.4 (2C0 ₂ Me); 75.1; 74.7; 74.0 (CqS); 51.9; 51.7, 51.0 (CHS); 51.5 (20Me); 48.3; 47.4; 47.0; 46.1; 37.9; 37.75; 37.71; 37.0; 36.8; 36.76; 36.71; 34.2; 29.47; 29.45; 29.36; 29.24; 29.17; 29.06; 28.9; 25.0 (20CH ₂ ).

HRMS calcd for C27H48O4S2: 500.2994; found: 500.2989. Method ΙΓ:

To a degassed solution of dixanthate obtained above (0.4 g, 0.57 mmol) in ethanol (2 mL) is added at 0 ° C pyrrolidine (0.15 mL, 3 equivalents).

The reaction mixture is stirred at 0 ° C until complete disappearance of the starting dixanthate (TLC: petroleum ether / ethyl acetate: 8/2).

The mixture is then acidified with an ethanolic solution of HCl.

After evaporation of the ethanol under a stream of nitrogen, extraction with diethyl ether, drying over sodium sulfate and evaporation under reduced pressure of the solvent, the oil obtained is crystallized in petroleum ether to yield the dithiospiroketal in the form of diastereoisomers.

^J H NMR was identical to previously isolated dithiospirocétal (Γ method). EXAMPLE 2

Preparation of 9,9 '- ((2S, 5R) -1,6-Dithiaspiro [4,4] nonane-2,7-diyl) dinonanoic acid

A mixture of Ο, Ο'-diethyl S, S '- (2-oxopropane-1,3-diyl) dicarbonodithioate bisxanthate (2.4 g, 8.05 mmol) and 10-undecenoic acid (3.86 g; 20.8 mmol, 2.6 equivalents) in ethyl acetate (4.7 mL) is refluxed under nitrogen for 10 minutes.

Dilauroyl peroxide (DLP) (10 mol%, 0.320 g) is then added and the reaction medium is refluxed for 3 hours.

5 mol% of DLP (0.16 g) is then added and the reaction mixture is allowed to reflux for 3 hours. The solvent is evaporated under reduced pressure and the residue is dissolved in ethanol (8 mL).

The solution is degassed and ethylenediamine (2.15 mL, 4 equivalents) is added at 0 ° C.

The reaction medium is left overnight in the refrigerator and then acidified with aqueous HCl solution (6N).

After filtration of the solution, the filtrate is extracted three times with diethyl ether and saturated NaCl solution. The organic phases are dried over sodium sulfate, filtered and evaporated to give a residue which is purified on a silica gel column using an elution gradient (petroleum ether / Et ₂ 0: 10/0 to 1/9 ) to give 0.850 g (22% over three steps) of dithiospiroketal as a mixture of diastereoisomers after recrystallization from methanol.

NMR (400 MHz, CDCl ₃ ) δ 9.89 (bs, 2H, 2 COOH); 3.64 (m, 0.5H, 0.5 CHS); 3.55 (m, 0.5H, 0.5 CHS); 3.40 (m, 1H, CHS); 2.38-2.06 (t + m, J = 7.5 Hz, 10H, 5 CH ₂ ); 1.88-1.47 (m, 10H, 5CH ₂ ); 1.27 (bs, 20H, 10CH ₂ ).

¹³ C NMR (101 MHz, CDCl3) δ 180.4 (2CO); 75.2; 74.8; 74.0 (CqS); 51.9; 51.7; 51.1 (2CHS); 48.3; 47.4; 47.0; 46.1; 37.9; 37.8; 37.7; 37.0; 36.9; 36.8; 36.7; 34.2; 29.5; 29.4; 29.2; 29.1; 29.06; 29.03; 28.9; 24.7.

HRMS calcd for C ₂₅ H ₄ 40 ₄ S _2: 472.2681; found: 472,2679. EXAMPLE 3

Preparation of S, S '- (1,25-Dihydroxy-13-oxopentacosane-10,16-diyl) Ο, Ο-diethyl dicarbonodithioate

A mixture of Ο, Ο'-diethyl S, S '- (2-oxopropane-1,3-diyl) dicarbonodithioate bisxanthate (2.4 g, 8.05 mmol) and 10-undecenol (3.87 mL; 33 mmol, 2.4 equivalents) in ethyl acetate (4 mL) is refluxed under nitrogen for 10 minutes.

Dilauroyl peroxide (DLP) (10 mol%, 0.320 g) is then added.

Then, every 2 hours, 5% (0.16 g) of DLP (2 x 0.16 g) is added.

The reaction, followed on tlc (petroleum ether / Et ₂ O: 7/3) is complete after a total addition of 20% DLP.

The solvent is then evaporated under reduced pressure and the residue obtained is purified on a column of silica gel using a solvent gradient (petroleum ether / Et ₂ 0: 10/0 to 0/10) to give 4.3 g (84%) di-addition product as a mixture of diastereoisomers.

NMR (400 MHz, CDCl ₃ ) δ 4.63 (qd, J = 7.1, 4H, 20C% CH ₃ ); 3.73-3.66 (m, 2H, 2CHS); 3.63 (t, J = 6.7 Hz, 4H, 2C% OH); 2.55 (t, J = 7.7 Hz, 4H, 2C% CO); 2.41 (bs, 2H, 20H); 2, 10-2.01 (m, 2H, 2CHHCHS); 1.83-174 (m, 2H, 2CHHCHS); 1.64 (q, J = 7.4 Hz, 4H, 2CH ₂ ); 1.59-1.50 (m, 4H, 2CH ₂ ); 1.41 (t, J = 7.1Hz, 6H, 20CH ₂ C¾); 1.43-1.26 (m + s, 24H, 12CH ₂ ).

¹³ C NMR (101 MHz, CDCl3) δ 214.7 (2CS); 209.3 (CO); 70.0 (20CH ₂ CH ₃ ); 63.1 (2CH ₂ OH); 51.14; 51.11 (2CHS); 40.0; 39.9; 34.7; 32.7; 29.5; 29.43; 29.41; 28.0; 26.8; 25.7 (20CH ₂ ); 13.9 (20CH ₂ CH ₃ ). Preparation of 9,9 '- ((2S, 5R) -1,6-dithiaspiro [4,4] non-2,7-diyl) dinonanoic acid

To a degassed solution of dixanthate obtained above (4.245 g, 6.64 mmol) in ethanol (7 mL) is added at 0 ° C ethylenediamine (1.77 mL, 4 equivalents).

The reaction mixture is stirred at room temperature until the total disappearance of the starting bisxanthate (tlc: petroleum ether / diethyl ether: 6/4).

The mixture is then neutralized with a solution of HC1 (6N). After filtration of the solution, the filtrate is extracted three times with diethyl ether and a saturated solution of

NaCl.

The organic phases are dried over sodium sulfate, filtered and evaporated to give 2.6 g of a white solid which is recrystallized from a mixture of diethyl ether and petroleum ether to give 2.1 g (71% over two steps) of dithiospiroketal as a mixture of diastereoisomers.

NMR (400 MHz, CDCl ₃ ) δ 3.63 (t, J = 6.6 Hz, 4.5H, ₂ CH ₂ OH, 0.5 CHS); 3.56 (m, 0.5H, 0.5 CHS); 3.40 (m, 1H, CHS); 2.40-2.16 (2m, 4H, 2CH ₂ ); 2.14-2.05 (m, 1H, CHH); 1.87-1.77 (m, 1H, CHH); 1.71-1.43 (m, 10Η, 5CH ₂ ); 1.26 (bs, 24H, 12CH ₂ ).

¹³ C NMR (101 MHz, CDCl3) δ 75.1; 74.7; 73.9 (CqS); 63.0 (2CH ₂ OH); 51.9; 51.7; 51.0 (2CHS); 48.3; 47.3; 46.9; 46.0; 37.9; 37.73; 37.70; 36.9; 36.8; 36.7; 36.6; 32.7; 29.55; 29.54; 29.49; 29.42; 29.05; 29.03; 28.92; 25.76 (20CH ₂ ).

HRMS calcd for C ₂₅ H ₄ 80 ₂ S _2: 444.3091; found: 444.3094.

EXAMPLE 4

Preparation of dimethyl (2,8-bis ((ethoxycarbonothioyl) thio) -5-oxononane-1,9-di-ddicarbamate

A mixture of Ο, Ο'-diethyl S, S '- (2-oxopropane-1,3-diyl) dicarbonodithioate bisxanthate (2.4 g, 8.05 mmol) and Carbamic acid, N-2-propen-1 -ylmethyl ester (2.77 g, 3 equivalents) in ethyl acetate (4 mL) is refluxed under nitrogen for 10 minutes. Dilauroyl peroxide (DLP) (10 mol%, 0.320 g) is then added.

Then, every 2 hours, 5% (0.16 g) of DLP (2 x 0.16 g) is added.

The reaction, followed on tlc (petroleum ether / Et ₂ O: 7/3), was terminated after a total addition of 20% DLP.

The solvent is then evaporated under reduced pressure and the residue obtained is purified on a column of silica gel using a solvent gradient (petroleum ether / Et ₂ 0: 10/0 to 1/9) to give 2.65 g (62%) diaddition product as an oil and a mixture of diastereoisomers as well as 0.774 g (23%) monoaddition product.

NMR (400 MHz, CDCl ₃ ) δ 5.14 (bs, 2H, 2NH); 4.63 (q, J = 7.1 Hz, 4H, 20CH 2 CH 3); 3.84-3.77 (m, 2H, 2CHS); 3.65 (s, 6H, 2CO, ₂ CH ₃ ); 3.53-3.38 (m, 4H, 2CH ₂ N), 2.60 (t, J = 7.2 Hz, 4H, 2CH ₂ CO); 2.10-2.01 (m, 2H, 2CHHCHS); 1.87-1.71 (m, 2H, 2CHHCHS); 1.42 (t, J = 7.1 Hz, 6H, 20 CH ₂ O¾).

¹³ C NMR (101 MHz, CDCl3) δ 213.3 (2CS), 208.5 (CO), 157.2 (2NHC0 ₂ ), 70.5 (20 CH ₂ CH ₃ ), 52.4, 51.1 ( 2CHS, 20Me), 44.3 (2CH ₂ ), 39.8 (2CH ₂ ), 24.9 (2CH ₂ ), 13.8 (20CH ₂ CH ₃ ).

Preparation of dimethyl (1,6-dithiaspiro [4,4] nonane-2,7-diylbis (methylene)) dicarbamate

To a degassed solution of dixanthate obtained above (2.65 g, 5 mmol) in ethanol (5 mL) is added at 0 ° C ethylenediamine (1.34 mL, 4 equivalents).

The reaction mixture is stirred at room temperature for 1 hour.

The mixture is then neutralized with a solution of HC1 (6N).

After filtration of the solution, the filtrate is extracted three times with diethyl ether and saturated NaCl solution. The organic phases are dried over sodium sulphate, filtered and evaporated to give 1.67 g of a white solid which is recrystallized from a mixture of diethyl ether and petroleum ether to give 0.47 g (28% on two parts). steps) of dithiospiroketal as a mixture of diastereoisomers.

Purification of the mother liquors on a column of silica gel using diethyl ether as eluent allowed to isolate 0.65 g (39%) of dithiospiroketal or a total of 67% in both steps. NMR (400 MHz, CDCl ₃ ) δ 5.2 (bs, 1Η, NH); 5.0 (bs, 1H, NH); 3.83-3.63 (m + bs, 8H, 2C0 ₂ Me, 2CHS); 3.48-3.15 (m, 4H, 2CH ₂ NH); 2.37-2.27 (m, 2H, CH ₂ ); 2.38-2.10 (m, 4H, 2CH ₂ ); 1.95-1.78 (m, 2H, CH ₂ ).

¹³ C NMR (101 MHz, CDCl3) δ 157.2; 157.1 (2NHCOO ₂ ); 76.2, 75.7, 75.3 (CqS), 52.3 (2C0 ₂ Me); 50.8; 50.7; 50.4; 50.3 (2CHS); 47.1; 46.5; 46.0; 45.9; 45.80; 45.5; 33.38; 33.34; 33.33; 33.30 (6CH ₂ ).

HRMS calcd for C13H22O4S2: 334.1021; found: 334.1016.

EXAMPLE 5

Preparation of 1,6-Dithiaspiro [4,4] non-2,7-diyldimethanamine dihydrochloride

A solution containing the carbamate derivative obtained in the preceding example

(0.2 g, 0.59 mmol) and ethanol (1 mL and 6N HCl (2 mL) were refluxed until the starting material had disappeared (tlc: Et ₂ O).

After co-evaporation with toluene under reduced pressure, the residue is crystallized from a mixture of methanol and diethyl ether to give the diamine derivative in the form of hydrochloride and mixture of diastereoisomers.

Ή NMR (400 MHz, CD ₄ 0) δ 3.89 to 3.81 (m, 1H, CHS), 3.76 to 3.67 (m, 1H, CHS), 3.62 (s, 1H, NH ₂ ), 3.28 (s, 1H, NH ₂ ), 3.24-3.13 (m, 2H, CH ₂ N), 3.09-2.97 (m, 2H, CH ₂ N), 2 , 47-2.18 (m, 6H, 3CH ₂ ), 2.05-1.89 (m, 2H, CH ₂ ).

¹³ C NMR (101 MHz, CD ₄ 0) δ 77.6; 77.4; 77.2 (Cq); 52.5; 48.4; 48.3; 48.1; 48.0 (2CHS); 47.3; 47.2; 46.5; 46.0; 45.9; 45.8; 45.7; 37.9; 34.98; 34.93; 34.83;

EXAMPLE 6

Preparation of di-tert-butyl (2,8-bis ((ethoxycarbonothioyl) thio) -5-oxononane-1,9-di-di-dicarbamate

A mixture of Ο, Ο'-diethyl S, S '- (2-oxopropane-1,3-diyl) dicarbonodithioate bisxanthate (2.4 g, 8.05 mmol) and tert-butyl-N-allyl carbamate (3, 0.4 g, 2.4 equivalents) in ethyl acetate (4 mL) is refluxed under nitrogen for 10 minutes.

Dilauroyl peroxide (DLP) (10 mol%, 0.320 g) is then added.

After 2 hours, 5% (0.16 g) of DLP are added.

The solvent is then evaporated under reduced pressure and the resulting residue is purified on a silica gel column using a solvent gradient (petroleum ether / Et ₂ 0: 10/0 to 1/9) to give 1. 52 g (31%) di-addition product in the form of an oil and a mixture of diastereoisomers as well as the monoaddition product (2.18 g, 59%).

NMR (400 MHz, CDCl ₃ ) δ 4.88 (bs, 2H, 2NH); 4.63 (q, 4H, 20 CH ₂ CH ₃ ); 3.80 (m, 2H), 2CHS); 3.45 (m, 2H, 2CHHNH); 3.34 (m, 2H, 2CHHNH); 2.60 (t, 4H, 2CH ₂ CO); 2.04 (m, 2H, 2CHHCHS); 1.80 (m, 2H, 2CHHCHS); 1.44-1.40 (t + s, 24H, 20CH ₂ C¾, 2CMe ₃ ).

¹³ C NMR (101 MHz, CDCl ₃ ) δ 213.4 (2CS); 208.5 (CO); 155.9 (2NHCOO ₂ ); 79.6 (2 <¾Me ₃ ); 70.4 (20CH ₂ CH ₃ ); 51.3 (2CHS); 43.7 (2CH ₂ ); 39.8 (2CH ₂ ); 28.4 (2Me ₃ ); 25.1 (2CH ₂ ); 13.8 (20CH ₂ CH ₃ ).

Preparation of di-tert-Butylil, 6-dithiaspirof 4,4'-nonane-2,7-diis-Ibis (methylene) dicarbamate

To a degassed solution of dixanthate obtained above (1.38 g, 2.25 mmol) in ethanol (4 mL) is added at 0 ° C. ethylenediamine (0.6 mL, 4 equivalents).

The reaction mixture is stirred at room temperature until the total disappearance of the starting dixanthate.

The mixture is then treated with a citric acid solution and extracted three times with diethyl ether.

The solvent is then evaporated under reduced pressure and the residue obtained (0.850 g) is purified by chromatography on silica gel using a solvent gradient (petroleum ether / AcOEt: 7/3 to 3/7) to yield the dithiospiroketal ( 0.675 g, 71%).

NMR (400 MHz, CDCl ₃ ) δ 4.94 (bs, 1H, NH); 4.80 (bs, 1H, NH); 3.83-3.72 (m, 1H, CHS); 3.69-3.64 (m, 1H, CHS); 3.44-3.31 (m, 2H, C¾NH); 3.24; 3.19 (m, 1H, CHHNH); 3.14-3.07 (m, 1H, CHHNH); 2.38-2.09 (m, 4H, 2CH ₂ ); 1.96-1.79 (m, 4H, 2CH ₂ ); 1.44 (s, 18H, 2CMe ₃ ).

¹³ C NMR (101 MHz, CDC1 ₃₎ δ 156.0; 155.9 (2NHCOO ₂ ); 79.5 (2CqMe ₃ ); 76.1; 75.7; 75.3 (CqS); 51.0; 50.9; 50.6 (2CHS); 47.1; 46.5; 46.1; 45.6; 33.5; 33.4 (6CH ₂ ); 28.6; 28.4 (CMe ₃ ).

HRMS calcd for C19H34N2O4S2: 418.1960; found: 418.1957.

EXAMPLE 7 Preparation of 2, 7-Bihydroxynonyl-1,6-dithiaspiro [4,4] nonane 1,1,6,6-tetraoxide

To a solution of dithiospiroketal as obtained in Example 3 (0.15 g, 0.34 mmol) in dichloromethane (4 mL) is added 75-70% m-chloroperbenzoic acid (0.35 g). g, 4.2 equivalents).

The reaction medium is stirred at ambient temperature (cc:

ACOEt / petroleum ether: 8/2) then filtered.

The filtrate is washed with sodium bisulfite solution followed by sodium bicarbonate and water to provide the desired bis (sulfone) as a white solid and a mixture of diastereoisomers in quantitative yield.

NMR (400 MHz, CDCl ₃ ) δ 3.65 (t, J = 6.6 Hz, 4H, 2 C% OH); 3.57 (m,

0.5H, 0.5CHS); 3.46 (m, 0.5H, 0.5 CHS); 3.17 (m, 1H, CHS); 2.87 - 2.67 (m, 2H, CH ₂ ); 2.41 - 2.31 (m, 2H, CH ₂ ); 2.13 - 1.93 (m, 6H, 3CH ₂ ); 1.77 - 1.30 (m + bs, 32H, I 6CH 2).

¹³ C NMR (101 MHz, CDCl ₃ ) δ 81.9; 81.0; 79.9 (Cq); 62.9 (2CH ₂ OH); 62.8; 59.2; 58.0 (2CHS0 ₂ ); 32.5; 29.8; 29.5; 29.4; 29.3; 29.2; 29.1; 27.4; 27.0; 26.95; 26.92; 26.88; 26.82; 26.1; 26.0; 25.7; 24.6; 24.1; 23.6; 23.5 (20CH ₂ ).

MS (ESI, m / z) 531 (M + Na) ⁺ . EXAMPLE 8

Preparation of S, S '- (1,9-Bis (2-hydroxymethyl) -5-oxononane-2,8-diyl) Ο, Ο-dibenzyl dicarbonodithioate

A mixture of Ο, Ο'-diethyl S, S '- (2-oxopropane-1,3-diyl) dicarbonodithioate bisxanthate (2.4 g, 8.05 mmol) and 2-Allyloxyethanol (2.57 mL; 15 mmol; 3 equivalents) in ethyl acetate (4 mL) is refluxed under nitrogen for 10 minutes.

Dilauroyl peroxide (DLP) (10 mol%, 0.320 g) is then added.

The reaction is monitored by thin layer chromatography (TLC) (petroleum ether / AcOEt: 4/6).

After adding 20 mol% to the total of DLP, the solvent is evaporated under reduced pressure and the residue obtained is purified on a column of silica gel using a solvent gradient (petroleum ether / AcOEt: 10/0 to 1 / 9) to give 2.67 g (66%) of a light yellow oil corresponding to the di-addition product as a mixture of diastereoisomers.

NMR (400 MHz, CDCl ₃ ) δ 4.63 (q, J = 7.2 Hz, 4H, 20C% CH ₃ ); 3.94 - 3.87 (m, 2H, 2CHS); 3.73 - 3.69 (m + t, J = 4.6 Hz, 6H, 2CH ₂ OH, 2CHHO); 3.64 - 3.53 (m, 6H, 2CHHO, 2CH ₂ O); 2.60 (t, J = 7.2 Hz, 4H, 2CH ₂ CO); 2.45 (s, 2H, 20H); 2.27 - 2.18 (m, 2H, 2CHHCHS); 1.88 - 1.78 (m, 2H, 2CHHCHS); 1.41 (t, J = 7.1Hz, 6H, 20CH ₂ CH ₃ ).

¹³ C NMR (101 MHz, CDCl3) δ 213.97; 213.95 (2CS); 209.1 (CO); 72.9; 72.4; 70.3 ( ₄ CH ₂ 0, 20 CH ₂ CH ₃ ); 61.8 (2CH ₂ OH); 50.06, 50.03 (2CHS); 39.9 (2CH ₂ CO); 24.8 (2CH ₂ CHS); 13.9 (20CH ₂ CH ₃ ).

HRMS (Hi MC ₆ ₂ 0 ₂ S ₄₎ ⁺ calcd for Ci ₃ H ₂₂ N0 _5: 258.1462; found: 258,1464. Preparation of 2,2 '- ((7,6-dithiaspiro [4 ^' .4] nonane-2 ^' , 7-diylbis (methylene)) bis (oxy)) diethanol To a degassed solution of S, S '- (1,9-bis (2-hydroxyethoxy) -5-oxononane-2,8-diyl) Ο, Ο'-diethyl dicarbonodithioate (1 g, 2 mmol) in ethanol (4 mL) is added at 0 ° C ethylenediamine (0.53 mL, 4 equivalents).

The reaction mixture is stirred until the total disappearance of the starting dixanthate.

The mixture is then treated with a solution of citric acid and NaCl and extracted three times with ethyl acetate.

The solvent is then evaporated off under reduced pressure and the residue obtained is purified on a column of silica gel using a solvent gradient (petroleum ether / AcOEt: 10/0, 4/6 and 0/10) to give 0.445 g. (72%) of a colorless oil and a mixture of diastereoisomers.

NMR (400 MHz, CDCl ₃ ) δ 3.89 - 3.80 (m, 1H, CHS); 3.77 - 3.49 (m, 13H, CHS, 4CH ₂ OCH ₂ , 2CH ₂ OH); 2.42-1.86 (m, 4CH ₂ , 20H).

¹³ C NMR (101 MHz, CDCl3) δ 75.5; 75.1; 75.0; 74.9; 74.8 (CqS, ₂ CH ₂ O); 72.4; 72.3; 72.2 (2CH ₂ O); 61.65, 61.60 (2CH ₂ O); 49.7; 49.4; 49.2; 49.1 (2CHS); 46.5; 46.1; 45.8; 45.4; 32.77; 32.71 (4CH ₂ ).

HRMS (M) ⁺ calcd for C13H24O4S2: 308.1116; found: 308.1127.

EXAMPLE 9

Preparation of tert-Butyl (2,6-bis ((ethoxycarbonothioyl) thio) -5-oxohexyl) carbamate

A solution of S- (3-chloro-2-oxopropyl) O-ethyl carbonodithioate (1 g, 4.69 mmol) and tert-butyl N-allyl carbamate (6.71 g, 41.94 mmol) in acetate of ethyl (4.7 mL) is refluxed under nitrogen for 10 minutes and then DLP (0.187 g, 10 mol%) is added.

After 1 hour, an addition of 5 mol% (0.094 g) is added and the reflux maintained for 40 minutes.

The solvent is evaporated and the residue is dissolved in acetone (8 mL). The potassium salt of ethyl xanthogenate (0.826 g, 1.1 equivalents) is added and the reaction mixture is stirred at room temperature under nitrogen. After evaporation of the acetone and extraction with dichloro-methane, the residue is purified on a column of silica gel using a solvent gradient (petroleum ether / AcOEt: 10/0 to 8/2) to give the desired dixanthate under form of a yellow oil (0.81 g, 38% on both stages).

NMR (400 MHz, CDCl ₃ ) δ 4.85 (s, 1H, NHCO 2); 4.63 (2q, 4H,

2OCH2CH3); 3.98 (s, 2H, CH ₂ S); 3.83 (m, 1H, CHS); 3.47 (m, 1H, CHHN); 3.37 (m, 1H, CHHN); 2.82 (t, J = 7.1 Hz, 2H, CH ₂ CO); 2.11 (m, 1H, CHHCHS); 1.86 (m, 1H, CHHCHS); 1.44-1.39 (m + t, 15H, Me ₃ , 20 CH ₂ O¾).

¹³ C NMR (101 MHz, CDCl 3) δ 213.2; 213.1 (2CS); 202.2 (CO); 155.9 (NHCO2); 79.5 (CqMe ₃ ); 70.9; 70.3 (20CH ₂ CH ₃ ); 53.5; 51.0; 45.3; 43.6; 38.9; 28.3; 25.0; (CHS, 4CH ₂ ); 13.8; 13.7 (20CH ₂ CH ₃ ).

HRMS (M ⁺⁾ calculated for Ci4H ₂₃ N0 ₄ S2 (MC ₃ H ₆ OS _2): 333.1076; find :

333.1075.

Preparation of methyl 17-fethan-butoxycarbonyl) amino) -10 6-bis (thethoxycarbonothioyl) thio) -13-oxoheptadecanoate

A mixture of tert-butyl (2,6-bis ((ethoxycarbonothioyl) thio) -5-oxohexyl) carbamate (1.44 g, 3.16 mmol) and methyl-10-undecenoate (1.42 mL; 32 mmol; 2 equivalents) in ethyl acetate (3.2 mL) is refluxed under nitrogen for 10 minutes.

Dilauroyl peroxide (DLP) (10 mol%, 0.126 g) is then added.

After 1 hour and 30 minutes, an addition of 5 mol% (0.063) is made and heating is continued for 2 hours.

The reaction is monitored on thin layer chromatography (TLC) (petroleum ether / AcOEt: 7/3).

The solvent is then evaporated under reduced pressure and the residue obtained is purified on a column of silica gel using a solvent gradient (petroleum ether / AcOEt: 10/0 to 8/2) to give 1.73 g (84%). %) oily adduct in the form of a mixture of diastereoisomers. Ή NMR (400 MHz, CDCl ₃ ) δ 4.86 (bs, 1Η, NH); 4.67 (m, 4H, 20 CH ₂ CH ₃ ); 3.84 - 3.77 (m, 1H, CHS); 3.73 - 3.67 (m, 1H, CHS); 3.66 (s, 3H, C0 ₂ Me); 3.52 - 3.41 (m, 1H, CHHNH); 3.39 - 3.29 (m, 1H, CHHN); 2.63 - 2.53 (m, 4Η, 2CH ₂ ); 2.30 (t, J = 7.8 Hz, 2H, CH 2 CO); 2.10 - 1.99 (m, 2H, CH ₂ ); 1.84 - 1.75 (m, 2H, CH ₂ ); 1.66 - 1.57 (m, 4H, 2CH ₂ ); 1.44 - 1.40 (m, 16H, 20 CH ₂ CH ₃ , ₅ CH ₂ ); 1.27 (bs, 9H, CMe ₃ ).

¹³ C NMR (101 MHz, CDC1 ₃₎ δ 214.5; 213.3 (2CS); 208.7 (CO); 174.2 (C0 ₂ Me); 155.8 (NHCO); 79.4 (<¾Me ₃ ); 70.2; 69.8 (20CH ₂ CH ₃ ); 51.4; 51.2; 51.0; 50.9 (OMe, 2CHS); 43.6 (CH ₂ N); 39.87; 39.85; 39.69; 34.6; 34.0; 29.26; 29.17; 29.09; 29.02 (CH ₂ ); 28.3 (C e ₃ ); 27.9; 26.7; 25.0; 24.8 (CH ₂ ); 13.79; 13.74 (20CH ₂ CH ₃ ). Preparation of Methyl 9- (7 - (((tert-butoxycarbonyl) amino) methyl) -1,6-dithiaspiro [4.4] nonan-2-yl) nonanoate

To a degassed solution of dixanthate obtained above (1.73 g, 2.65 mmol) in ethanol (3 mL) is added at 0 ° C ethylenediamine (0.71 mL, 4 equivalents).

The solvent is then evaporated off under reduced pressure and the residue obtained (1.2 g) is purified by chromatography on silica gel (toluene / AcOEt: 98/2) to give the dithiospiroketal (0.85 g, 70%) in the form a colorless oil and a mixture of diastereoisomers and rotamers.

NMR (400 MHz, CDCl ₃ ) δ 4.86 (bd, 1H, NH); 3.82 - 3.06 (m, 4H, 2CHS, CH 2 NH); 3.64 (s, 3H, OMe); 2.38 - 2.02 (m, 6H, 3CH ₂ ); 2.27 (t, J = 7.6 Hz, 2H, CH ₂ CO); 1.97 - 1.52 (m, 6H, 3CH ₂ ); 1.41 (s, 9H, CqMe ₃ ); 1.25 (bs, 10H, 5CH ₂ ).

¹³ C NMR (101 MHz, CDC1 ₃₎ δ 174.3 (C0 ₂ Me); 156.0; 155.9 (NHCO); 79.4 (C ₃ Me); 75.6; 75.3; 75.0; 74.6 (CqS); 51.7; 51.6; 51.49; 51.2; 51.1; 51.0; 50.9; 50.3 (2CHS, OMe); 47.7; 47.1; 46.8; 46.2; 45.9; 45.7 (NCH ₂ ); 37.75; 37.72; 37.65; 37.62; 36.9; 36.8; 36.7; 34.1; 33.5; 33.4; 33.3; 29.42; 29.40; 29.3; 29.2; 29.1; 29.0; 28.98; 28.85; 28.83; 24.9 (12 CH ₂ ); 28.4 (C e ₃ ).

HRMS (M) ⁺ calcd for C ₂₃ H ₄ NOS ₄ S ₂ : 459.2477; found: 459.2476.

Preparation of Methyl 9- (7- (aminomethyl) -1,6-dithiaspiro [4.4] nonan-2-yl) nonanoate

To a solution of NHBoc derivative above (0.235 g, 0.51 mmol) in a mixture of dichloromethane (0.8 mL) and methanol (0.2 mL) is added at 0 ° C trifluoroacetic acid ( 1 mL).

The reaction medium is stirred at ambient temperature until the starting material (tlc: petroleum ether / ACOEt: 8/2) disappears.

After evaporation of the reaction mixture under a stream of nitrogen, the residue is dissolved in diethyl ether and washed with 5% NaOH solution.

The organic phase is washed with water and dried over sodium sulfate. After evaporation of the solvent, the residue obtained is chromatographed on a column of silica gel using a solvent gradient (dichloromethane / methanol / triethylamine: 10/0/0, 9/1/0, 9/1 / 0.1) to give the free amine as a colorless oil (0.115 g, 63%).

NMR (400 MHz, CDCl ₃ ) (mixture of diastereoisomers) δ 3.80 - 3.35 (m, 2H, 2CHS); 3.64 (s, 3H, OMe); 2.96 - 2.66 (m, 4H, CH ₂ NH ₂ , NH ₂ ); 2.40 - 2.05 (m + t, J = 7.5 Hz, 8H, 3CH ₂ , CH ₂ CO ₂ Me); 1.96 - 1.41 (m, 6H, 3 CH ₂ ); 1.24 (bs, 10H, 5CH ₂ ).

¹³ C NMR (101 MHz, CDCl3) δ 174.3 (C0 ₂ Me); 75.3; 75.1; 74.8; 74.5 (2CqS); 53.8; 53.7; 53.1; 53.0; 51.7; 51.6; 51.3; 51.2 (2CHS); 51.5 (OMe); 47.8; 47.7; 47.52; 47.49; 47.44; 47.38; 47.2; 46.8; 46.7; 46.4; 46.1; 45.8; 37.8; 37.7; 37.6; 36.89; 36.79; 36.77; 36.73; 34.1; 33.6; 33.6; 33.5; 33.4; 29.4; 29.36; 29.33; 29.2; 29.1; 29.0; 28.9; 25.0 (CH ₂ ).

HRMS (M ⁺⁾ calculated for Ci8H ₃₃ N0 ₂ S _2: 359.1953; found: 359.1960.

A dimethyl ester monomer suspension as obtained in Example 1 (0.2 g, 0.4 mmol), hexamethylenediamine (0.0465 g, 0.4 mmol) and 1,5,7-triazabicyclo [ 4.4.0] dec-5-ene (2.8 mg, 5 mol%) in THF (2 mL) is degassed under nitrogen.

The solvent is then evaporated and the residue is heated at 100 ° C for 3 hours. Gaseous evolution is observed. The temperature is then brought to 150 ° C for 3 hours.

Cooling gives a slightly yellow transparent solid which is triturated in dichloromethane and then in diethyl ether by crushing the solid swollen with the solvent to give a white powder after decantation.

The IR spectrum in m-cresol reveals the presence of an amide function at 1633 cm- ¹ and the absence of a band corresponding to the methyl ester.

Thermogravimetric analysis (TGA) of the polymer obtained, performed on an apparatus "TGA Q50 V6.7 Build 203" (Figure 1) shows that this polymer has excellent thermal stability up to about 370 ° C. A POLYURETHANE

A mixture of dimethyl (1,6-dithiaspiro [4.4] nonane-2,7-diylbis (methylene)) dicarbamate (0.2 g, 0.6 mmol), 1,10-decanediol (0.104 g, 0.6 mmol) and 1,5,7-Triazabicyclo [4.4.0] dec-5-ene (4 mg, 5 mol%) is degassed in diethyl ether and then heated to 160 ° C under nitrogen. The polymer obtained is swollen in tetrahydrofuran. After evaporation of THF and drying, the polymer is dissolved in CDCl3. The spectrum of ^J H NMR shows the disappearance of OMe and the presence of CH2O.

¹ NMR (400 MHz, CDClI) 5.07 (bd, NH); 4.03 (m, CH ₂ O); 3.82 - 3.62 (m, CHS); 3.48 - 3.14 (m, CH ₂ N); 2.38 - 1.87 (m, CH ₂ ); 1.58 (bd, CH ₂ ); 1.29 (bd, CH ₂ ).

EXAMPLE 12 SYNTHESIS OF A POLYAMIDE

A mixture of methyl 9- (7- (aminomethyl) -1,6-dithiaspiro [4.4] nonan-2-yl) nonanoate (0.115 g, 0.32 mmol), and 1,5,7-triazabicyclo [4.4. 0] dec-5-ene (2.2 mg, 5 mol%) is degassed in THF and then heated at 160 ° C under nitrogen for 8 hours.

After evaporation of THF and drying, the polymer is dissolved in CDCl3.

The ^J H NMR spectrum (400 MHz, CDCl3) shows the virtual disappearance of OMe and the absence of CH ₂ NH ₂ and CH ₂ C0 ₂ Me.

Claims

1. Compound of formula (I):

in which :

R ₃ and R ₄ , which may be identical or different, represent a hydrogen atom or a C 1 -C 6 -alkyl optionally substituted with a non-reactive functional group with respect to a thiocarbonylthio function; or R ₃ and R ₄ together form a cycloalkyl or a heterocycloalkyl optionally substituted with a carbonyl function;

-R ₅ and Re, which may be identical or different, represent a hydrogen atom, or an optionally substituted C 1 -C 15 -alkyl, or R ₅ and R ₉ together form a cycloalkyl or a heterocycloalkyl, optionally substituted with a carbonyl function;

n and n ', which are identical or different, are equal to 0, 1 or 2; and its isomeric forms, in particular racemic, enantiomeric and diastereoisomeric.

2. Compound according to claim 1, wherein W and Y, which are identical or different, represent a functional group chosen from -OR, -COOR, -C (= O) R, -CO-O-CO-R, -CO- O-NRR ', -O-COOR, -NRR', -CN, -CR = NR ', -CO-NRR', -CO-NR-OR ',

-NR-COOR ', -NR-CO-NR'R ", -N = C = O, -SR or -S (= O) R, -S (= O) ₂ R, -S (= O) ₂ OR, -S (= O) ₂ NRR ', -P (= O) (OR) ₂ , -P (= O) (OR) (NR'R "), -P (= O) (NRR') ₂ with R, R 'and R ", identical or different, representing a hydrogen atom, a C 1 -C 12 -alkyl, or a cycloalkyl, an aryl or a heteroaryl.

A compound according to any one of the preceding claims, wherein W and Y, identical or different, represent a functional group selected from -OR, -COOR, -NR-COOR 'or -NRR', with R and R ', identical or different, representing a hydrogen atom or a C 1 -C 12 -alkyl.

A compound according to any one of the preceding claims wherein R 1 and R ₂ , which are the same or different, represent a C 1 -C 18 alkyl chain, and preferably a C 1 -C 10 alkyl chain.

5. A compound according to any one of the preceding claims, wherein R ₃ and R ₄ represent a hydrogen atom.

6. A compound according to any one of the preceding claims, wherein n and n 'are the same, and in particular are 0 or 2.

A compound according to any one of the preceding claims, wherein W and Y are the same, and R 1 and R ₂ are the same.

8. Compound according to any one of the preceding claims, characterized in that it is chosen from:

The compound of any one of claims 1 to 6, wherein W and Y are different.

10. Compound according to any one of claims 1 to 6 or 9, characterized in that it is chosen from:

A process for preparing a compound according to any one of claims 1 to 8, wherein W and Y are the same, and R 1 and R ₂ are the same, comprising at least the following steps:

A) bringing into contact a compound of formula (1) below:

in which :

R ₃ and R ₄ , which may be identical or different, represent a hydrogen atom or a C 1 -C 6 alkyl optionally substituted with a non-reactive functional group with respect to a thiocarbonylthio function; or R ₃ and R ₄ together form a cycloalkyl or a heterocycloalkyl optionally substituted with a carbonyl function; and

in which :

-Ri represents a C1-C25-alkyl chain optionally interrupted by one or more oxygen, nitrogen, sulfur and / or silicon atoms, and / or by one or more optionally substituted aryl or heteroaryl; and

-R ₅ and Re, which may be identical or different, represent a hydrogen atom or an optionally substituted C 1 -C 15 -alkyl, or R ₅ and R ₅ together form a cycloalkyl or a heterocycloalkyl, optionally substituted by a carbonyl function, preferably R ₅ and Re represent a hydrogen atom; in the presence of a physicochemical initiator, and optionally a solvent, under conditions conducive to the formation of a compound of formula (3) below:

wherein W, Z, R ₁ , R ₃ , R ₄ , R ₅ , and Re are as defined above;

B) i) heating the reaction medium comprising said compound (3) or bringing said compound (3) into contact with a base, in particular chosen from sodium hydroxide, lithium hydroxide (LiOH), potassium hydroxide, an alcoholate, aqueous ammonia or an amine and preferably selected from ethylene diamine or pyrrolidine, and ii) contacting the reaction medium comprising said compound (3) with an organic or inorganic acid, the steps i) and ii) being carried out simultaneously or successively, preferably successively in the order i) then ii); under conditions conducive to the cyclization of said compound (3) to form the compound (4) of the following formula:

wherein W, R 1, R ₃ , R ₄ , R ₅ and Re are as defined above; and

12. Preparation process according to the preceding claim, further comprising a step of hydrolysis of the compound of formula (4) or (5).

Process for the preparation of a compound according to any one of claims 1 to 6 and 9 to 10, wherein W and Y are different, comprising at least the following steps:

A ') bringing into contact a compound of formula (6) below:

in which :

Z represents an optionally substituted C 1 -C 10 -alkyl, an optionally substituted cycloalkyl, an aryl, a heteroaryl, an optionally substituted C 1 -C 10 -alkoxy, an optionally substituted aryloxy, an optionally substituted C 1 -C 10 -alkylthio, an optionally substituted arylthio , or a radical NRR 'with R and R', which may be identical or different, representing an optionally substituted C 1 -C 10 -alkyl, an optionally substituted cycloalkyl, an aryl or a heteroaryl, and preferably Z represents a C 1 -C 10 -alkoxy or a optionally substituted aryloxy radical; and

with at least one equivalent of a compound (7) of the following formula:

in which : -W represents a non-reactive functional group with respect to a thiocarbonylthio function;

-R ₅ and Re, which may be identical or different, represent a hydrogen atom or an optionally substituted C 1 -C 15 -alkyl, or R 5 and 5 together form a cycloalkyl or a heterocycloalkyl, optionally substituted with a carbonyl function, preferably R 5 and 5 represent a hydrogen atom; in the presence of a physicochemical initiator, and optionally a solvent, under conditions conducive to the formation of a compound of formula (8) below:

z

(8)

wherein W, Z, G, R 1, R 3, R ₄ , R 5 and 5 are as defined above;

B ') bringing into contact said compound of formula (8) obtained at the end of step A') with a salt of the thiocarbonylthio compound of formula ZC (= S) MS, in which Z is as defined above and M represents an alkali metal, an alkaline earth metal or an ammonium, and preferably a sodium or potassium, under conditions conducive to the formation of a compound of formula (9) below:

z (9)

wherein W, Z, R 1, R 3, R ₄ , R 5 and 5 are as defined above;

in which :

R ₂ represents a C 1 -C 25 alkyl chain optionally interrupted by one or more oxygen, nitrogen, sulfur and / or silicon atoms, and / or by one or more optionally substituted aryl or heteroaryl groups; and

-R ₅ and Re, which may be identical or different, represent a hydrogen atom or an optionally substituted C 1 -C 15 -alkyl, or R ₅ and 5 together form a cycloalkyl or a heterocycloalkyl, optionally substituted by a carbonyl function, preferably R 5 and 5 represent a hydrogen atom; in the presence of a physicochemical initiator, and optionally a solvent, under conditions conducive to the formation of a compound of formula (11) below:

^Z (H)

wherein W, Y, R 1, R ₂ , R ₃ , R 4, R 5, R 6 and Z are as defined above;

wherein W, Y, R 1, R ₂ , R ₃ , R 4, R 5 and 5 are as defined above; E ') Optionally, bringing said compound (12) into contact with an oxidant, in particular a peracid, under conditions that are effective for the formation of the compound (13) of the following formula:

14. A process according to claim 11, wherein the physicochemical initiator is chosen from peroxidic agents, agents that are sensitive to visible light or UV light, and preferably is a peroxide, in particular dilauroyl peroxide or di-t-butyl peroxide.

15. Preparation process according to any one of claims 11 to 14, wherein step A) or A ') is carried out in a solvent medium, in particular selected from water, ethyl acetate, ethyl acetate and the like. t-butyl alcohol, chlorobenzene, t-butyl methyl ether, acetic acid, 1,2-dichloroethane, or an alkane such as cyclohexane, heptane or octane, and preferably acetate ethyl.

16. Preparation process according to any one of claims 11 to 14, wherein step A) or A ') is carried out without an accompanying solvent medium.

17. Use of a compound according to any one of claims 1 to 10 as a monomeric compound.

18. A polymer derived from the homopolymerization or the copolymerization of compound of formula (I) according to any one of claims 1 to 10.

19. Polymer according to claim 18, characterized in that it is of formula (II)

in which :

-W and Y ', identical or different, derive from a functional group as defined in claim 1;

-A represents a monomeric entity distinct from a monomeric entity derived from a compound according to any one of claims 1 to 10;

-p is 0 or 1;

R 1, P 2, P 3, P 4, P 5, R 6, n and n 'are as defined in claim 1.

20. Polymer according to claim 18, characterized in that W and Y 'are chosen from -O-, -CO-O-, -C (= O) -, -CO-O-CO- , -CO-O-NR-, -O-CO-O-, -NR-, -CR = N-, -CO-NR-, -CO-NR-O-, -NR-CO-O-, - NR-CO-NR'-, -S- or -S (= O) -, -S (= O) ₂ -, -S (= O) ₂ O-, -S (= O) ₂ NR-, - P (= 0) (OR) 0-, -P (= O) (OR) NR'-, - P (= O) (NRR ') NR'-, with R and R', identical or different, representing a hydrogen atom, a C ₁ -C ₂ alkyl, or a cycloalkyl, an aryl or a heteroaryl.

21. Polymer according to any one of claims 18 to 20, characterized in that it is chosen from:

47