Dyeing composition containing a thiol/disulphide fluorescent colorant comprising amine groups and having an internal cationic charge, and method for lightening keratin materials using said colorant

0001The invention relates to the coloring of keratin materials using fluorescent thiol / disulfide dyes comprising one or more amino groups.

0002It is known to dye keratin fibers, in particular human fibers, by direct coloring. The method conventionally used in direct dyeing consists in applying to the keratin fibers direct dyes which are colored and coloring molecules having an affinity for the fibers, in letting them diffuse, then in rinsing the fibers.

0003The direct dyes which are conventionally used are, for example, dyes of the benzene nitro type, anthraquinone dyes, nitropyridines, dyes of the azo, xanthene, acridine, azine or triaryl methane type.

0004The colorings which result from the use of direct dyes are temporary or semi-permanent dyes because the nature of the interactions which bind the direct dyes to the keratin fiber, and their desorption from the surface and / or from the core of the fiber are responsible. their low dye power and their poor resistance to washing or perspiration.

0005Furthermore, the coloring of keratin fibers from conventional direct dyes does not make it possible to lighten the keratin fibers significantly.

0006The lightening of the color of keratin fibers, more particularly dark towards lighter shades, possibly modifying the shade thereof, constitutes an important demand.

0007Conventionally, to obtain a lighter coloring, a chemical bleaching process is used. This process consists in treating keratin materials such as keratin fibers, in particular the hair, with a strong oxidizing system, generally consisting of hydrogen peroxide associated or not with persalts, most often in an alkaline medium.

0008This bleaching system has the drawback of degrading keratin materials, in particular keratin fibers, in particular human fibers such as the hair, and altering their cosmetic properties. The fibers tend to become rough, more difficult to disentangle and more fragile. Finally, the lightening or discoloration of keratin fibers by oxidizing agents is incompatible with treatments for modifying the shape of said fibers, particularly in hair straightening treatments.

0009Another lightening technique is to apply fluorescent direct dyes to dark hair. This technique described in particular in documents<patcit id="pcit0001" dnum="FR2830189"><text>FR 2830189</text></patcit> and <patcit id="pcit0002" dnum="WO2004091473A"><text>WO 2004/091473</text></patcit> respects the quality of the keratin fiber during the treatment, but the fluorescent dyes used do not have satisfactory resistance to shampooing.

0010To increase the toughness of direct dyes, it is known to fix direct dyes by covalent bonding to the hair. For example, it is known to react dyes with reactive groups with very numerous cystine or cysteine ​​residues in keratin fibers, see for example<nplcit id="ncit0001" npl-type="s"><text>Journal of the Society of Dyers and Colourists, Guise and Stapleton, 91, 259-264 (1975</text></nplcit>); <nplcit id="ncit0002" npl-type="s"><text>Journal of Cosmetic Chemistry, 42, 1-17 (1991</text></nplcit>); <patcit id="pcit0003" dnum="CA2024509"><text>CA 2024509</text></patcit>;

0011In addition, it is known to protect the thiol function or functions contained in a molecule to be grafted to the hair before applying them to said hair. <patcit id="pcit0004" dnum="WO9951194A"><text>WO 99/51194</text></patcit>. However, this application does not mention the use of fluorescent dyes for coloring or lightening hair.

0012Other disulfide dyes known for coloring keratin fibers are disulfide derivatives of aminothiophenol derivatives. Such dyes are described for example in the patent<patcit id="pcit0005" dnum="FR1156407"><text>FR 1156407</text></patcit>. These dyes can be used in relatively mild conditions, in the presence of a slightly reducing medium or after a reducing pretreatment of the hair. However, these dyes can cause color changes during application.

0013Finally, the document <patcit id="pcit0006" dnum="WO2005097051A"><text>WO 2005/097051</text></patcit> describes aza-imidazolium disulfide dyes for the direct dyeing of keratin fibers.

0014The object of the present invention is to provide new systems for coloring keratin materials, in particular human keratin fibers, in particular the hair, which do not have the drawbacks of existing bleaching methods. In particular, one of the aims of the present invention is to provide direct coloring systems making it possible to obtain lightening effects in particular on naturally or artificially dark keratin fibers, tenacious in the face of successive shampoos, which do not degrade the keratin fibers and which do not alter their cosmetic properties.

0015This object is achieved with the present invention which relates to a process for coloring keratin materials, in particular keratin fibers, in particular human fibers such as the hair, more particularly dark hair, consisting in applying to the keratin materials, a dye composition. , comprising in a suitable cosmetic medium, at least one fluorescent thiol dye, chosen from the dyes of formulas (I) and (II) below:<chemistry id="chem0001" num="0001"><img file="EP2004757B1_D0001.tif" /></chemistry><chemistry id="chem0002" num="0002"><img file="EP2004757B1_D0002.tif" /></chemistry>their organic or mineral acid salts, optical isomers, geometric isomers, and solvates such as hydrates; formulas (I) and (II) in which:<ul id="ul0001" list-style="none" compact="compact"><li>➢ R and R "', identical or different, represent a hydroxy group, an amino group (NR_atR_b) or ammonium (N⁺R_atR_bR_vs), Year^-; with R_at, R_b and R_vs, identical or different, representing a hydrogen atom or a group (C₁-VS₄) alkyl; or two R alkyl groups_at and R_b of the amino or ammonium group form a heterocycle comprising from 5 to 7 members and optionally comprising another heteroatom identical or different to that of the nitrogen atom such as morpholinyl, piperazinyl, piperidinyl, pyrrolyl, morpholinium, piperazinium, piperidinium, pyrrolinium, and an^- representing an anionic counterion;</li><li>➢ R 'and R ", identical or different, represent a hydrogen atom or a group as defined for R and R"' respectively;</li><li>➢ R_g, R '_g, R "_g, R "'_g, R_h, R '_h, R "_h and R '' '_h, identical or different, represent a hydrogen atom, a halogen atom, an amino group, (di) (C₁-VS₄) alkylamino, cyano, carboxy, hydroxy, trifluoromethyl, acylamino, C alkoxy₁-VS₄, (poly) hydroxyalkoxy in C₂-VS₄, (VS₁-VS₄) alkylcarbonyloxy, (C₁-VS₄) alkoxycarbonyl, (C₁-VS₄) alkylcarbonylamino, acylamino, carbamoyl, (C₁-VS₄) alkylsulfonylamino, an aminosulfonyl radical, or a (C₁-VS₁₆) alkyl optionally substituted by a group chosen from (C₁-VS₁₂) alkoxy, hydroxy, cyano, carboxy, amino, (di) (C₁-VS₄) alkylamino, or the two alkyl radicals carried by the nitrogen atom of the amino group form a heterocycle comprising from 5 to 7 members and optionally comprising another heteroatom identical or different to that of the nitrogen atom; particularly R_g, R '_g, R "_g, R "'_g, R_h, R '_h, R "_h and R "'_h represent a hydrogen atom or a group (C₁-VS₄) alkyl;</li><li>➢ R '_i, R "_i, R "'_i and R ""_i, identical or different, represent a hydrogen atom, or a group (C₁-VS₄) alkyl; particularly R '_i, R "_i, R "'_i, and R ""_i represents a hydrogen atom;</li><li>➢ m, m ', identical or different, represent an integer inclusive between 1 and 10; particularly an integer inclusive between 2 and 4; preferably m and m 'are worth 2;</li><li>➢ p, p ', q and q', identical or different, represent an integer inclusive between 1 and 6;</li><li>➢ M 'representing an anionic counterion; and</li><li>➢ Y represents: i) a hydrogen atom; ii) an alkali metal; iii) an alkaline earth metal; iv) an ammonium group: N⁺R^αR^βR^γR^δ or a phosphonium group: P⁺R^αR^βR^γR^δ with R^α, R^β, R^γ and R^δ, identical or different, representing a hydrogen atom or a group (C₁-VS₄) alkyl; or v) a protective group of thiol function;</li></ul>Being heard that :<ul id="ul0002" list-style="dash" compact="compact"><li>when the compound of formula <b>(I)</b> or <b>(II)</b> contains other cationic parts, it is associated with one or more anionic counterions allowing to reach the electroneutrality of the formula <b>(I)</b> or <b>(II).</b></li></ul>

0016Another subject of the invention is a dye composition comprising, in an appropriate cosmetic medium at least one fluorescent dye of formula <b>(I)</b> or <b>(II)</b> as defined above, and a reducing agent.

0017The invention also relates to new fluorescent dyes of formula (I) or (II) as defined above. The dyeing method according to the invention makes it possible to visibly color dark keratin materials, in particular dark human keratin fibers, in particular dark hair.

0018In addition, the process of the invention makes it possible to obtain a coloration of keratin materials, in particular human keratin fibers, especially the hair, without degrading said material, which is persistent with regard to shampoos, common attacks (sun, perspiration). , and other hair treatments. The process of the invention also makes it possible to obtain a lightening of keratin materials such as keratin fibers, particularly dark keratin fibers and more particularly dark hair.

0019For the purposes of the invention, the expression “dark keratinous material” is understood to mean that which has a luminescence L * encrypted in the CIEL system L * a * b *, less than or equal to 45 and preferably less than or equal to 40, knowing moreover that L * = 0 is equivalent to black and L * = 100 to white.

0020For the purposes of the invention, the term “naturally or artificially dark hair” means hair whose pitch is less than or equal to 6 (dark blonde) and preferably less than or equal to 4 (chestnut).

0021The lightening of the hair is evaluated by the variation in "pitch" before and after application of the compound of formula <b>(I)</b> or <b>(II).</b>

0022The notion "tone" is based on the classification of natural shades, a tone separating each shade from the one that immediately follows or precedes it. This definition and classification of natural shades is well known to hair professionals and published in the book.<nplcit id="ncit0003" npl-type="b"><text>"Hair treatment science" by Charles ZVIAK 1988, Ed. Masson, p. 215 and 278</text></nplcit>.

0023The pitch of the tone ranges from 1 (black) to 10 (very light blonde), a unit corresponding to a tone; the higher the number, the lighter the shade.

0024An artificially colored hair is a hair whose color has been modified by a coloring treatment, for example coloring with direct dyes or oxidation dyes.

0025Preferably, the composition must, after application to hair, for example brown, lead to the results below.<ul id="ul0003" list-style="dash" compact="compact"><li>We are interested in the reflectance performance of hair when it is irradiated with visible light in the wavelength range from 400 to 700 nanometers.</li><li>The reflectance curves are then compared as a function of the wavelength, of hair treated with the composition of the invention and of untreated hair.</li><li>The curve corresponding to the treated hair must show a reflectance in the wavelength range from 500 to 700 nanometers greater than the curve corresponding to the untreated hair.</li><li>This means that, in the wavelength range from 540 to 700 nanometers, there is at least one range where the reflectance curve corresponding to the treated hair is greater than the reflectance curve corresponding to the untreated hair. The term "superior" means a difference of at least 0.05% of reflectance, and preferably of at least 0.1%. This does not prevent that it can exist in the wavelength range from 540 to 700 nanometers, at least one range where the reflectance curve corresponding to the treated hair is superimposable, or less than the reflectance curve corresponding to the untreated hair.</li></ul>

0026Preferably, the wavelength where the difference is maximum between the reflectance curve of the treated hair and that of the untreated hair, is in the wavelength range from 500 to 650 nanometers, and preferably in the wavelength range from 550 to 620 nanometers.

0027Within the meaning of the present invention, and unless a different indication is given:<ul id="ul0004" list-style="dash" compact="compact"><li>the “aryl” or “heteroaryl” radicals or the aryl or heteroaryl part of a radical may be substituted by at least one substituent carried by a carbon atom, chosen from:<ul id="ul0005" list-style="bullet" compact="compact"><li>a C 1 alkyl radical₁-VS₁₆, preferably in C₁-VS₈, optionally substituted by one or more radicals chosen from hydroxy, C alkoxy radicals₁-VS₂, (poly) -hydroxyalkoxy in C₂-VS₄, acylamino, amino substituted by two alkyl radicals, identical or different, at C₁-VS₄, optionally carrying at least one hydroxy group or, the two radicals being able to form, with the nitrogen atom to which they are attached, a heterocycle comprising from 5 to 7 members, preferably from 5 to 6 members, optionally saturated or unsaturated substituted optionally comprising another heteroatom identical or different from nitrogen;</li><li>a halogen atom such as chlorine, fluorine or bromine;</li><li>a hydroxy group;</li><li>a C alkoxy radical₁-VS₂ ;</li><li>a C alkylthio radical₁-VS₂;</li><li>a (poly) -hydroxyalkoxy radical in C₂-VS₄ ;</li><li>an amino radical;</li><li>a 5- or 6-membered heterocycloalkyl radical;</li><li>an optionally cationic 5 or 6-membered heteroaryl radical, preferably imidazolium, and optionally substituted by a radical (C₁-VS₄) alkyl, preferably methyl;</li><li>an amino radical substituted by one or two identical or different C 1 alkyl radicals₁-VS₆ possibly carrying at least:<ol id="ol0001" compact="compact"><li>i) a hydroxy group,</li><li>ii) an amino group optionally substituted by one or two C 1 alkyl radicals₁-VS₃ optionally substituted, said alkyl radicals being able to form, with the nitrogen atom to which they are attached, a heterocycle comprising from 5 to 7 members, saturated or unsaturated optionally substituted optionally comprising at least one other heteroatom different or not from nitrogen,</li></ol></li><li>-NR-COR 'in which the radical R is a hydrogen atom, a C 1 alkyl radical₁-VS₄ optionally carrying at least one hydroxy group and the radical R 'is a C 1 alkyl radical₁-VS₂ ;</li><li>(R)₂N-CO- in which the radicals R, which may or may not be identical, represent a hydrogen atom, a C 1 alkyl radical₁-VS₄ optionally carrying at least one hydroxy group;</li><li>R'SO₂-NR- in which the radical R represents a hydrogen atom, a C 1 alkyl radical₁-VS₄ optionally carrying at least one hydroxy group and the radical R ′ represents a C 1 alkyl radical₁-VS₄, a phenyl radical;</li><li>(R)₂N-SO₂- in which the radicals R, which may or may not be identical, represent a hydrogen atom, a C 1 alkyl radical₁-VS₄ optionally carrying at least one hydroxy group,</li><li>a carboxylic radical in acid or salified form (preferably with an alkali metal or ammonium, substituted or not);</li><li>a cyano group;</li><li>a polyhaloalkyl group comprising from 1 to 6 carbon atoms and from 1 to 6 halogen atoms, which may be identical or different, the polyhaloalkyl group is for example trifluoromethyl;</li></ul></li><li>the cyclic or heterocyclic part of a non-aromatic radical can be substituted by at least one substituent carried by a carbon atom chosen from the groups:<ul id="ul0006" list-style="bullet" compact="compact"><li>hydroxy,</li><li>C alkoxy₁-VS₄,</li><li>(poly) hydroxyalkoxy in C₂-VS₄,</li><li>a C alkylthio radical₁-VS₂;</li><li>RCO-NR'- in which the radical R 'is a hydrogen atom, a C 1 alkyl radical₁-VS₄ optionally carrying at least one hydroxy group and the radical R is a C 1 alkyl radical₁-VS₂, amino substituted by two identical or different C alkyl groups₁-VS₄ optionally carrying at least one hydroxy group;</li><li>RCO-O- in which the radical R is a C 1 alkyl radical₁-VS₄, amino substituted by one or two identical or different C alkyl groups₁-VS₄ optionally carrying at least one hydroxy group, said alkyl radicals being able to form, with the nitrogen atom to which they are attached, a heterocycle comprising from 5 to 7 members, saturated or unsaturated optionally substituted optionally comprising at least one other different heteroatom or not nitrogen;</li><li>RO-CO- in which the radical R is a C 1 alkyl radical₁-VS₄ optionally carrying at least one hydroxy group;</li></ul></li><li>a cyclic, heterocyclic radical, or a non-aromatic part of an aryl or heteroaryl radical, can also be substituted by one or more oxo or thioxo groups;</li><li>an “aryl” radical represents a mono or polycyclic group, condensed or not, comprising from 6 to 22 carbon atoms, and of which at least one ring is aromatic; preferably the aryl radical is a phenyl, biphenyl, naphthyl, indenyl, anthracenyl, or tetrahydronaphthyl;</li><li>a “diarylalkyl” radical represents a group comprising on the same carbon atom of an alkyl group two aryl groups, identical or different, such as diphenylmethyl or 1,1-diphenylethyl;</li><li>a “heteroaryl radical” represents a mono or polycyclic group, condensed or not, optionally cationic, comprising from 5 to 22 links, from 1 to 6 heteroatoms chosen from the nitrogen, oxygen, sulfur and selenium atom, and of which at least one cycle is aromatic; preferably heteroaryl is selected from acridinyl, benzimidazolyl, benzobistriazolyl, benzopyrazolyl, benzopyridazinyle, benzoquinolyl, benzothiazolyl, benzotriazolyl, benzoxazolyl, pyridinyl, tetrazolyl, dihydrothiazolyl, imidazopyridinyl, imidazolyl, indolyl, isoquinolyl, naphthoimidazolyle, naphthooxazolyle, naphthopyrazolyle, oxadiazolyl, oxazolyl, oxazolopyridyl , phenazinyl, phenooxazolyl, pyrazinyl, pyrazolyl, pyrilyl, pyrazoyltriazyle, pyridyle, pyridinoimidazolyle, pyrrolyle, quinolyle, tétrazolyle, thiadiazolyle, thiazolyle, thiazolopyridinyle, thiazoylimidazolyle, thiopyrylyl, triazolyle, xanthylyl and its ammonium salt;</li><li>a “diheteroarylalkyl” radical represents a group comprising on the same carbon atom of an alkyl group two heteroaryl groups, identical or different such as difurylmethyl, 1,1-difurylethyl, dipyrrolylmethyl, dithienylmethyl;</li><li>a “cyclic radical” is a non-aromatic, mono or polycyclic cycloalkyl radical, condensed or not, containing from 5 to 22 carbon atoms, which may contain from 1 to several unsaturations; in particular the cyclic radical is a cyclohexyl;</li><li>a “sterically hindered cyclic” radical is a cyclic radical, aromatic or not, substituted or not, hindered by steric effect or constraint, comprising from 6 to 14 links, which can be bridged, as sterically hindered radicals, mention may be made of bicyclo [ 1.1.0] butane, mesytyles such as 1,3,5-trimethylpnenyl, 1,3,5-triterbutylphenyl, 1,3,5-isobutylphenyl, 1,3,5-trimetylsillylphenyl and adamantyl;</li><li>a “heterocyclic or heterocycle radical” is a mono or polycyclic non aromatic radical, condensed or not, containing from 5 to 22 links, comprising from 1 to 6 heteroatoms chosen from the nitrogen, oxygen, sulfur and selenium;</li><li>an “alkyl radical” is a C hydrocarbon radical₁-VS₁₆, linear or branched, preferably in C₁-VS₈ ;</li><li>the expression “optionally substituted” attributed to the alkyl radical means that said alkyl radical may be substituted by one or more radicals chosen from the radicals i) hydroxy, ii) alkoxy at C₁-VS₄, iii) acylamino, iv) amino optionally substituted by one or two alkyl radicals, identical or different, at C₁-VS₄, said alkyl radicals being able to form, with the nitrogen atom which carries them, a heterocyle comprising from 5 to 7 members, optionally comprising another heteroatom different or not from nitrogen; v) or a quaternary ammonium group -N R'R "R" ', M for which R', R ", R" ', identical or different, represent a hydrogen atom, or a C alkyl group₁-VS₄, or else -N⁺R'R "R" 'forms a heteroaryl such as imidazolium optionally substituted by a group C₁-VS₄ alkyl, and M^- represents the counterion of the organic, mineral acid or of the corresponding halide,</li><li>an “alkoxy radical” is an alkyl-oxy or alkyl-O- radical for which the alkyl radical is a hydrocarbon radical, linear or branched, at C₁-VS₁₆ preferably in C₁-VS₈;</li><li>an "alkylthio radical" is an alkyl-S- radical for which the alkyl radical is a linear or branched C hydrocarbon radical₁-VS₁₆ preferably in C₁-VS₈ ; when the alkylthio group is optionally substituted, this means that the alkyl group is optionally substituted as defined above;</li><li>the limits delimiting the extent of a range of values ​​are included in this range of values;</li><li>a “salt of organic or inorganic acid” is more particularly chosen from a salt derived from i) hydrochloric acid HCl, ii) hydrobromic acid HBr, iii) sulfuric acid H₂SO₄, iv) alkylsulfonic acids: Alk-S (O)₂OH such as methylsulfonic acid and ethylsulfonic acid; v) arylsulfonic acids: ArS (O)₂OH such as benzene sulfonic acid and toluene sulfonic acid; vi) citric acid; vii) succinic acid; viii) tartaric acid; ix) lactic acid, x) alkoxysulfinic acids: Alk-OS (O) OH such as methoxysulfinic acid and ethoxysulfinic acid; xi) aryloxysulfinic acids such as tolueneoxysulfinic acid and phenoxysulfinic acid; xii) phosphoric acid H₃PO₄; xiii) acetic acid CH₃COOH; xiv) CF triflic acid₃SO₃H and xv) tetrafluoroboric acid HBF₄ ;</li><li>an “anionic counterion” is an anion or an anionic group associated with the cationic charge of the dye; more particularly the anionic counterion is chosen from i) halides such as chloride, bromide; ii) nitrates; iii) sulfonates including C₁-VS₆ alkylsulfonates: Alk-S (O)₂O^- such as methylsulfonate or mesylate and ethylsulfonate; iv) arylsulfonates: Ar-S (O)₂O^- such as benzenesulfonate and toluenesulfonate or tosylate; v) citrate; vi) succinate; vii) tartrate; viii) lactate; ix) alkyl sulfates: Alk-OS (O) O^- such as methysulfate and ethylsulfate; x) arylsulfates: Ar-OS (O) O^- such as benzenesulfate and toluenesulfate; xi) alkoxysulfates: Alk-OS (O)₂O^- such as methoxy sulfate and ethoxysulfate; xii) aryloxysulfates: Ar-OS (O)₂O^-, xiii) phosphate; xiv) acetate; xv) triflate; and xvi) borates such as tetrafluoroborate.</li></ul>

0028The fluorescent dyes of formula <b>(I)</b> or <b>(II)</b> are compounds capable of absorbing in UV or visible radiation at a wavelength λ_abs between 250 and 800 nm and capable of re-emitting in the visible range at an emission wavelength λ_em between 400 and 800 nm.

0029Preferably the thiol fluorescent compounds of the invention are dyes capable of absorbing in the visible λ_abs between 400 and 800 nm and reemitting in the visible λ_em between 400 and 800 nm. More preferably the fluorescent dyes of formula<b>(I)</b> or <b>(II)</b> are dyes capable of absorbing at a λ_abs between 420 nm and 550 nm and reemitting in the visible at a λ_em between 470 and 600 nm.

0030The fluorescent compounds of formula (II) of the invention contain a SY function which can be in the covalent form -SY or ionic form -S^- Y⁺ depending on the nature of Y and the pH of the medium.

0031A particular mode relates to thiol fluorescent dyes with group of formula (II) with SY function where Y represents a hydrogen atom, or an alkali metal. Advantageously Y represents a hydrogen atom.

0032In accordance with another particular embodiment of the invention, in the formula <b>(II)</b> above, Y is a protective group known to those skilled in the art, for example those described in the works <nplcit id="ncit0004" npl-type="b"><text>"Protective Groups in Organic Synthesis", TW Greene, John Willey &amp; Sons ed., NY, 1981, pp.193-217</text></nplcit> ; <nplcit id="ncit0005" npl-type="b"><text>"Protecting Groups", P. Kocienski, Thieme, 3rd ed., 2005, chap. 5</text></nplcit>.

0033Particularly when Y represents a protective group for the thiol function, Y is chosen from the following radicals:<ul id="ul0007" list-style="none" compact="compact"><li>■ (C₁-VS₄) alkylcarbonyl;</li><li>■ (C₁-VS₄) alkylthiocarbonyl;</li><li>■ (C₁-VS₄) a) coxycarbonyl;</li><li>■ (C₁-VS₄) alkoxythiocarbonyl;</li><li>■ (C₁-VS₄) alkylthio-thiocarbonyl; ^.</li><li>■ (di) (C₁-VS₄) (alkyl) aminocarbonyl;</li><li>■ (di) (C₁-VS₄) (alkyl) aminothiocarbonyl;</li><li>■ arylcarbonyl as phenylcarbonyl;</li><li>■ aryloxycarbonyl;</li><li>■ aryl (C₁-VS₄) alkoxycarbonyl;</li><li>■ (di) (C₁-VS₄) (alkyl) aminocarbonyl such as dimethylaminocarbonyl;</li><li>■ (C₁-VS₄) (alkyl) arylaminocarbonyl;</li><li>■ carboxy;</li><li>■ N / A₃^-, M⁺ with M⁺ representing an alkali metal such as sodium or potassium, or else M 'of formula (II) and M⁺ are absent;</li><li>■ optionally substituted aryl such as phenyl, dibenzosuberyl, or 1,3,5-cycloheptatrienyl,</li><li>■ optionally substituted heteroaryl; including in particular the cationic or non-cationic heteroaryl, comprising from 1 to 4 following heteroatoms:<ol id="ol0002" compact="compact"><li>i) 5-, 6- or 7-membered monocyclics such as furanyl or furyl, pyrrolyl or pyrryl, thiophenyl or thienyl, pyrazolyl, oxazolyl, oxazolium, isoxazolyl, isoxazolium, thiazolyl, thiazolium, isothiazolyl, isothiazolium, 1,2,4-triazol 1,2,4-triazolium, 1,2,3-triazolyle, 1,2,3-triazolium, 1,2,4-oxazolyle, 1,2,4-oxazolium, 1,2,4-thiadiazolyle, 1, 2,4-thiadiazolium, pyrylium, thiopyridyle, pyridinium, pyrimidinyle, pyrimidinium, pyrazinyle, pyrazinium, pyridazinyle, pyridazinium, triazinyl, triazinium, tetrazinyl, tetrazinium, azepine, azepinium, oxazepinyl, oxazepinium, thieepinyl, thieepinium, imidazolyl, imidazolium;</li><li>ii) 8 to 11-membered bicyclics such as indolyl, indolinium, benzoimidazolyl, benzoimidazolium, benzoxazolyl, benzoxazolium, dihydrobenzoxazolinyl, benzothiazolyl, benzothiazolium, pyridoimidazolyl, pyridoimidazolium or thienocycloheptadienyl groups, or thienocycloheptadienic groups) VS₁-VS₄) alkyl such as methyl, or polyhalo (C₁-VS₄) alkyl such as trifluoromethyl;</li><li>iii) or tricyclic <u>ABC</u> following :<chemistry id="chem0003" num="0003"><img file="EP2004757B1_D0003.tif" /></chemistry>in which the two cycles <u>AT,</u><u>VS</u> possibly have a heteroatom, and the cycle <u>B</u> is a 5, 6 or 7-membered ring, particularly a 6-membered ring and contains at least one heteroatom such as pyperidyl, pyranyl;</li></ol></li><li>■ heterocycloalkyl optionally substituted, optionally cationic, the heterocycloalkyl group represents in particular a saturated or partially saturated monocyclic group with 5, 6 or 7 members comprising from 1 to 4 heteroatoms chosen from oxygen, sulfur and nitrogen, such as di / tetrahydrofuranyl, di / tetrahydrothiophenyl, di / tetrahydropyrrolyle, di / tetrahydropyranyl, di / tetra / hexahydrothiopyranyl, dihydropyridyl, piperazinyl, piperidinyl, tetramethylpiperidinyl, morpholinyl, di / tetra / hexahydroazepinyl, di / tetrahydropyrimidinyl these groups being optionally substituted by one or more groups such as (C₁-VS₄) alkyl, oxo or thioxo; or the heterocycle represents the following grouping:<chemistry id="chem0004" num="0004"><img file="EP2004757B1_D0004.tif" /></chemistry>in which R '^vs, R '^d, R '^e, R '^f, R '^g and R '^h, identical or different, represent a hydrogen atom or a group (C₁-VS₄) alkyl, or two groups R '^g with R '^h, and / or R '^e with R '^f form an oxo or thioxo group, or else R '^g with R '^e together form a cycloalkyl; and v represents an integer inclusive between 1 and 3; preferably R '^vs at R '^h represent a hydrogen atom; and an^- represents a counterion;</li><li>■ isothiouronium -C (NR '^vsR '^d) = N⁺R '^eR '^f; Year^- with R '^vs, R '^d, R '^e and R '^f, identical or different, represent a hydrogen atom or a group (C₁-VS₄) alkyl; preferably R '^vs at R '^f represent a hydrogen atom; and an^- represents a counterion;</li><li>■ isothiourea -C (NR '^vsR '^d) = NR '^e; with R '^vs, R '^d, and R '^e as defined above;</li><li>■ (di) aryl (C₁-VS₄) optionally substituted alkyl such as 9-anthracenylmethyl, phenylmethyl or diphenylmethyl optionally substituted by one or more groups in particular chosen from (C₁-VS₄) alkyl, (C₁-VS₄) alkoxy such as methoxy, hydroxy, (C₁-VS₄) alkylcarbonyl, (di) (C₁-VS₄) (alkyl) amino such as dimethylamino;</li><li>■ (di) heteroaryl (C₁-VS₄) optionally substituted akyl, the heteroaryl group is in particular, cationic or not, monocyclic, comprising 5 or 6 members and from 1 to 4 heteroatoms chosen from nitrogen, oxygen and sulfur, such as the pyrrolyl, furanyl, thiophenyl groups , pyridyl, pyridyl N-oxide such as 4-pyridyl or 2-pyridyl-N-oxide, pyrylium, pyridinium, triazinyl, optionally substituted by one or more groups such as particularly methyl alkyl, advantageously (di) heteroaryl (C₁-VS₄) akyl is (di) heteroarylmethyl or (di) heteroarylethyl;</li><li>■ CR¹R²R³ with R¹, R² and R³ identical or different, representing a halogen atom or a group chosen from:<ul id="ul0008" list-style="dash" compact="compact"><li>(VS₁-VS₄) alkyl;</li><li>(VS₁-VS₄) alkoxy;</li><li>optionally substituted aryl such as phenyl optionally substituted by one or more groups such as (C₁-VS₄) alkyl, (C₁-VS₄) alkoxy, hydroxy;</li><li>optionally substituted heteroaryl such as thiophenyl, furanyl, pyrrolyl, pyranyl, pyridyl, optionally substituted by a group (C₁-VS₄) alkyl;</li><li>P (Z¹) R '¹R '²R '³ with R '¹, and R '² identical or different represent a hydroxy group, (C₁-VS₄) alkoxy or alkyl, R '³ represents a hydroxy group or (C₁-VS₄) alkoxy, and Z¹ represents an oxygen or sulfur atom;</li></ul></li><li>■ sterically hindered cyclic such as the adamantyl group; and</li><li>■ alkoxy (C₁-VS₄) optionally substituted alkyl such as methoxymethyl (MOM), ethoxyethyl (EOM) and isobutoxymethyl.</li></ul>

0034According to a particular embodiment, the protected thiol fluorescent dyes of formula (II) comprise a group Y i) heteroaryl monocyclic with 5 or 6 aromatic, cationic links comprising from 1 to 4 heteroatoms chosen from oxygen, sulfur and nitrogen , such as oxazolium,, isoxazolium, thiazolium, isothiazolium, 1,2,4-triazolium, 1,2,3-triazolium, 1,2,4-oxazolium, 1,2,4-thiadiazolium, pyrylium, pyridinium, pyrimidinium, pyrazinyl, pyrazinium, pyridazinium, triazinium, tetrazinium, oxazepinium, thiepinyl, thieepinium, imidazolium; ii) cationic 8 to 11-membered bicyclic heteroaryl such as indolinium, benzoimidazolium, benzoxazolium, benzothiazolium, these mono or bicyclic heteroaryl groups being optionally substituted by one or more groups such as alkyl such as methyl, or polyhalo (C₁-VS₄) alkyl such as trifluoromethyl; iii) or following heterocyclic:<chemistry id="chem0005" num="0005"><img file="EP2004757B1_D0005.tif" /></chemistry>in which R '^vs and R '^d, identical or different, represent a hydrogen atom or a group (C₁-VS₄) alkyl; preferably R '^vs at R '^d represent a group (C₁-VS₄) alkyl such as methyl; and an^- represents a counterion.

0035Particularly Y represents a group chosen from oxazolium, isoxazolium, thiazolium, isothiazolium, 1,2,4-triazolium, 1,2,3-triazolium, 1,2,4-oxazolium, 1,2,4-thiadiazolium, pyrylium, pyridinium , pyrimidinium, pyrazinium, pyridazinium, triazinium and imidazolium, benzoimidazolium, benzoxazolium, benzothiazolium, these groups being optionally substituted by one or more groups (C₁-VS₄) alkyl, especially methyl.

0036In particular, Y represents an alkali metal or a protective group such as:<ul id="ul0009" list-style="none" compact="compact"><li>➢ (C₁-VS₄) alkylcarbonyl such as methylcarbonyl or ethylcarbonyl;</li><li>➢ arylcarbonyl as phenylcarbonyl;</li><li>➢ (C₁-VS₄) alkoxycarbonyl;</li><li>➢ aryloxycarbonyl;</li><li>➢ aryl (C₁-VS₄) alkoxycarbonyl;</li><li>➢ (di) (C₁-VS₄) (alkyl) aminocarbonyl such as dimethylaminocarbonyl;</li><li>➢ (C₁-VS₄) (alkyl) arylaminocarbonyl;</li><li>➢ optionally substituted aryl such as phenyl;</li><li>➢ 5- or 6-membered monocyclic heteroaryl such as imidazolyl or pyridyl;</li><li>➢ 5-6-membered cationic monocyclic heteroaryl such as pyrylium, pyridinium, pyrimidinium, pyrazinium, pyridazinium, triazinium, imidazolium; these groups being optionally substituted by one or more, identical or different, groups (C₁-VS₄) alkyl such as methyl;</li><li>➢ 8 to 11-membered cationic bicyclic heteroaryl such as benzoimidazolium, or benzoxazolium; these groups being optionally substituted by one or more, identical or different, groups (C₁-VS₄) alkyl such as methyl;</li><li>➢ cationic heterocycle of the following formula:<chemistry id="chem0006" num="0006"><img file="EP2004757B1_D0006.tif" /></chemistry></li><li>➢ isothiouronium -C (NH₂) = N⁺H₂; Year^-,</li><li>➢ isothiourea -C (NH₂) = NH; or</li><li>➢ N / A₃^-, M⁺ with M⁺ with M⁺ representing an alkali metal such as sodium or potassium, or else M 'of formula (II) and M⁺ are absent;</li></ul>

0037According to a particular embodiment of the invention, the dyes of the invention belong to the formula <b>(the)</b> or <b>(IIa)</b> which have an ethylene group connecting the pyridinium part to the phenyl in the ortho or para position of the pyridinium either in 2-4 ', 4-2', 4-4 ':<chemistry id="chem0007" num="0007"><img file="EP2004757B1_D0007.tif" /></chemistry>with R, R ', R ", R"', R_g, R '_g, R "_g, R '"_g, R_h, R '_h, R "_h, R "'_h, R_i, R "_i, R "'_i, R ""_i, m, m ', p, p', q, q ', Y and M' are as defined above. Particularly R_h, R "_h are ortho to the pyridinium group and R '_h, R "_h represent a hydrogen atom. Another aspect of the invention relates to the dyes of formula<b>(the)</b> or <b>(IIa)</b> having R groups_g, R "_g in position 3 'and R'_g/ 'R "_g which represent a hydrogen atom.

0038Advantageously the dyes of formula <b>(the)</b> and <b>(IIa)</b> have their amino group: R '(CH₂)_p-N- (CH₂)_q-R and / or R "(CH₂)_p-N- (CH₂)_{q '}-R '"in position 1'.

0039By way of example of thiol fluorescent dyes, mention may be made in particular of the following compounds:<tables id="tabl0001" num="0001"><table frame="all"><tgroup cols="2" colsep="0"><colspec colnum="1" colname="col1" colwidth="79mm" colsep="1" /><colspec colnum="2" colname="col2" colwidth="83mm" /><tbody><row><entry namest="col1" nameend="col2" align="center"><chemistry id="chem0008" num="0008"><img file="EP2004757B1_D0008.tif" /></chemistry></entry></row><row><entry namest="col1" nameend="col2" align="center"><b>1</b></entry></row><row><entry namest="col1" nameend="col2" align="center"><chemistry id="chem0009" num="0009"><img file="EP2004757B1_D0009.tif" /></chemistry></entry></row><row><entry namest="col1" nameend="col2" align="center"><b>2</b></entry></row><row><entry namest="col1" nameend="col2" align="center"><chemistry id="chem0010" num="0010"><img file="EP2004757B1_D0010.tif" /></chemistry></entry></row><row><entry namest="col1" nameend="col2" align="center"><b>3</b></entry></row><row><entry align="center"><chemistry id="chem0011" num="0011"><img file="EP2004757B1_D0011.tif" /></chemistry></entry><entry colsep="1" align="center"><chemistry id="chem0012" num="0012"><img file="EP2004757B1_D0012.tif" /></chemistry></entry></row><row><entry align="center"><b>4</b></entry><entry colsep="1" align="center"><b>5</b></entry></row><row><entry align="center"><chemistry id="chem0013" num="0013"><img file="EP2004757B1_D0013.tif" /></chemistry></entry><entry colsep="1" align="center"><chemistry id="chem0014" num="0014"><img file="EP2004757B1_D0014.tif" /></chemistry></entry></row><row><entry align="center"><b>6</b></entry><entry colsep="1" align="center"><b>7</b></entry></row><row><entry align="center"><chemistry id="chem0015" num="0015"><img file="EP2004757B1_D0015.tif" /></chemistry></entry><entry colsep="1" align="center"><chemistry id="chem0016" num="0016"><img file="EP2004757B1_D0016.tif" /></chemistry></entry></row><row><entry align="center"><b>8</b></entry><entry colsep="1" align="center"><b>9</b></entry></row><row><entry align="center"><chemistry id="chem0017" num="0017"><img file="EP2004757B1_D0017.tif" /></chemistry></entry><entry colsep="1" align="center"><chemistry id="chem0018" num="0018"><img file="EP2004757B1_D0018.tif" /></chemistry></entry></row><row><entry align="center"><b>10</b></entry><entry colsep="1" align="center"><b>11</b></entry></row><row><entry align="center"><chemistry id="chem0019" num="0019"><img file="EP2004757B1_D0019.tif" /></chemistry></entry><entry colsep="1" align="center"><chemistry id="chem0020" num="0020"><img file="EP2004757B1_D0020.tif" /></chemistry></entry></row><row><entry align="center"><b>12</b></entry><entry colsep="1" align="center"><b>13</b></entry></row><row><entry align="center"><chemistry id="chem0021" num="0021"><img file="EP2004757B1_D0021.tif" /></chemistry></entry><entry colsep="1" align="center"><chemistry id="chem0022" num="0022"><img file="EP2004757B1_D0022.tif" /></chemistry></entry></row><row><entry align="center"><b>14</b></entry><entry colsep="1" align="center"><b>15</b> (not covered by claims)</entry></row><row><entry align="center"><chemistry id="chem0023" num="0023"><img file="EP2004757B1_D0023.tif" /></chemistry></entry><entry colsep="1" align="center"><chemistry id="chem0024" num="0024"><img file="EP2004757B1_D0024.tif" /></chemistry></entry></row><row><entry align="center"><b>16</b></entry><entry colsep="1" align="center"><b>17</b></entry></row><row><entry align="center"><chemistry id="chem0025" num="0025"><img file="EP2004757B1_D0025.tif" /></chemistry></entry><entry colsep="1" align="center"><chemistry id="chem0026" num="0026"><img file="EP2004757B1_D0026.tif" /></chemistry></entry></row><row><entry align="center"><b>18</b></entry><entry colsep="1" align="center"><b>19</b></entry></row><row><entry align="center"><chemistry id="chem0027" num="0027"><img file="EP2004757B1_D0027.tif" /></chemistry></entry><entry colsep="1" align="center"><chemistry id="chem0028" num="0028"><img file="EP2004757B1_D0028.tif" /></chemistry></entry></row><row><entry align="center"><b>20</b></entry><entry colsep="1" align="center"><b>21</b></entry></row><row><entry align="center"><chemistry id="chem0029" num="0029"><img file="EP2004757B1_D0029.tif" /></chemistry></entry><entry colsep="1" align="center"><chemistry id="chem0030" num="0030"><img file="EP2004757B1_D0030.tif" /></chemistry></entry></row><row><entry align="center"><b>22</b></entry><entry colsep="1" align="center"><b>23</b></entry></row><row><entry align="center"><chemistry id="chem0031" num="0031"><img file="EP2004757B1_D0031.tif" /></chemistry></entry><entry colsep="1" align="center"><chemistry id="chem0032" num="0032"><img file="EP2004757B1_D0032.tif" /></chemistry></entry></row><row><entry align="center"><b>24</b></entry><entry colsep="1" align="center"><b>25</b></entry></row><row><entry align="center"><chemistry id="chem0033" num="0033"><img file="EP2004757B1_D0033.tif" /></chemistry></entry><entry colsep="1" align="center"><chemistry id="chem0034" num="0034"><img file="EP2004757B1_D0034.tif" /></chemistry></entry></row><row><entry align="center"><b>26</b></entry><entry colsep="1" align="center"><b>27</b></entry></row><row><entry align="center"><chemistry id="chem0035" num="0035"><img file="EP2004757B1_D0035.tif" /></chemistry></entry><entry colsep="1" align="center"><chemistry id="chem0036" num="0036"><img file="EP2004757B1_D0036.tif" /></chemistry></entry></row><row><entry align="center"><b>28</b></entry><entry colsep="1" align="center"><b>29</b></entry></row><row><entry namest="col1" nameend="col2" align="center"><chemistry id="chem0037" num="0037"><img file="EP2004757B1_D0037.tif" /></chemistry></entry></row><row><entry namest="col1" nameend="col2" align="center"><b>30</b></entry></row><row><entry namest="col1" nameend="col2" align="center"><chemistry id="chem0038" num="0038"><img file="EP2004757B1_D0038.tif" /></chemistry></entry></row><row><entry namest="col1" nameend="col2" align="center"><b>31</b></entry></row><row><entry namest="col1" nameend="col2" align="center"><chemistry id="chem0039" num="0039"><img file="EP2004757B1_D0039.tif" /></chemistry></entry></row><row><entry namest="col1" nameend="col2" align="center"><b>32</b></entry></row></tbody></tgroup></table></tables>with M 'representing an anionic counterion.

0040Protected thiol dyes of formula <b>(II ')</b> can be synthesized in two stages. The first step of preparing the unprotected thiol dye<b>(II-H)</b> according to methods known to those skilled in the art, for example <nplcit id="ncit0006" npl-type="b"><text>"Thiols and organic Sulfides", "Thiocyanates and Isothiocyanates, organic", Ullmann's Encyclopedia, Wiley-VCH, Weinheim, 2005</text></nplcit>. And the second step consisting in protecting the thiol function according to the conventional methods known by a person skilled in the art to lead to the protected thiol dyes of formula<b>(II ').</b> As an example to protect the thiol -SH function of the thiol dye, the methods of the works can be used <nplcit id="ncit0007" npl-type="b"><text>"Protective Groups in Organic Synthesis", TW Greene, John Willey &amp; Sons ed., NY, 1981, pp.193-217</text></nplcit>; <nplcit id="ncit0008" npl-type="b"><text>"Protecting Groups", P. Kocienski, Thieme, 3rd ed., 2005, chap. 5</text></nplcit>.

0041We can illustrate this method by the method consisting of i) generating thiol fluorescent dyes of formula <b>(<u>II-H)</u></b> by reduction of a fluorescent dye with two chromophores, carrying a disulfide function -SS- (I ') and ii) to be protected by conventional methods, said thiol function from <b><u>(II-H)</u></b> with the reagent <b><u>7</u></b> Y'R to access the protected thiol fluorescent dyes of formula <b>(II ').</b> The thiol compound <u><b>6</b></u> can also be metallized with an alkali or alkaline earth metal Met * to yield the fluorescent thiolate dye of formula (II ").<chemistry id="chem0040" num="0040"><img file="EP2004757B1_D0040.tif" /></chemistry>with Y 'representing a protective group of thiol function; Met * representing an alkali metal or an alkaline earth metal, particularly sodium or potassium, it being understood that when the metal is an alkaline earth metal 2 chromophores with thiolate-S- function can be associated with 1 Metal²⁺; and with R, R ', R_g, R '_g, R_h, R '_h, R '_¡, R "_¡, m, p, q, and M 'are as defined above; Y 'represents a protective group of thiol function; and R of Y'R represents a leaving group nucleofuge, such as for example mesylate, tosylate, triflate or halide.

0042It is also possible to use a thiol reagent Y'-SH comprising a group Y 'as defined above whose nucleophilic function SH can react on the carbon atom in alpha of the halogen atom carried by the fluorescent chromophore <b><u>(at'</u>)</b>to yield the protected thiol fluorescent dye of formula (II '):<chemistry id="chem0041" num="0041"><img file="EP2004757B1_D0041.tif" /></chemistry>with R, R ', R_g, R '_g, R_h, R '_h, R '_i, R "_i, m, p, q, and M ', (II') are as defined above, and Hal representing a nucleofuge halogen atom such as bromine, iodine or chlorine.

0043More particularly, it is possible to replace a leaving nucleofuge group with a thiourea group (S = C (NRR) NRR) to generate the isothiouroniums. For example, if the thiourea group is a thioimidazolinium (β), the reaction scheme is as follows:<chemistry id="chem0042" num="0042"><img file="EP2004757B1_D0042.tif" /></chemistry>with R, R ', R_g, R '_g, R_h, R '_h, R '_i, R "_i, m, p, q, and M 'are as defined above. A variant is to use instead of the halide comprising the fluorescent chromophore<b><u>(at</u>')</b> a chromophore comprising another type of nucleofuge such as tosylate, mesylate.

0044By way of example, a compound containing a protected thiol group contains a leaving group nucleofuge R, such as for example mesylate, tosylate, or triflate which can undergo the nucleophilic attack of the amine carried by the fluorescent styrylic chromophore:<chemistry id="chem0043" num="0043"><img file="EP2004757B1_D0043.tif" /></chemistry>

0045Another alternative comes from the use of halides as a leaving nucleofuge group on a thiol compound which can be substituted by a primary amine function, for example carried by a fluorescent styrylic chromophore:<chemistry id="chem0044" num="0044"><img file="EP2004757B1_D0044.tif" /></chemistry>

0046According to another possibility, the thiol fluorescent dyes of formula (II) according to the invention can be obtained by reaction of a compound comprising a thiol group Y as defined above and an electrophilic group <b><u>(f)</u></b> with a pyridinium compound comprising a nucleophilic group. For example, an aldehyde, ketone or a thioaldehyde, thioketone can be condensed when G ′ represents an oxygen atom or a sulfur with an “activated methylene” such as alkylpyridinium.<b><u>(e)</u></b> to generate an ethylene bond> C = C <. This reaction is commonly called "Knoevenagel" condensation. By "activated methylenes" is meant those which preferably comprises in position 2 or 4 of the pyridinium group a methylene group R_¡-CH₂-: <chemistry id="chem0045" num="0045"><img file="EP2004757B1_D0045.tif" /></chemistry>with R, R ', R_g, R '_g, R_h, R '_h, R '_i, R "_¡, m, p, q, Y and M 'as defined above and G' representing an oxygen or sulfur atom.

0047We can refer to the book <nplcit id="ncit0009" npl-type="b"><text>Advanced Organic Chemistry, "Reactions, Mechanisms and Structures", J. March, 4th Ed, John Willey &amp; Sons, 1992</text></nplcit> or <nplcit id="ncit0010" npl-type="s"><text>TW Greene "Protective Groups in Organic Synthesis"</text></nplcit>, to have more details on the operating conditions implemented for the processes mentioned above.

0048The thiol fluorescent dyes formed can be transformed into thiol-fluorescent dyes protected -SY 'by the protection of thiol -SH using the conventional protective groups. The thiol fluorescent dyes are metallized also using the conventional methods known to those skilled in the art such as those described in<nplcit id="ncit0011" npl-type="b"><text>Advanced Organic Chemistry, "Reactions, Mechanisms and Structures", J. March, 4th Ed, John Willey &amp; Sons, NY, 1992</text></nplcit>.

0049The protected thiol dyes can be deprotected by conventional means such as those described in the works. <nplcit id="ncit0012" npl-type="b"><text>"Protective Groups in Organic Synthesis", TW Greene, John Willey &amp; Sons ed., NY, 1981</text></nplcit> ; <nplcit id="ncit0013" npl-type="b"><text>"Protecting Groups", P. Kocienski, Thieme, 3rd ed., 2005</text></nplcit>.

0050The starting reagents are commercial or accessible by conventional methods known to those skilled in the art. As an example, it is possible to synthesize the symmetrical thiol fluorescent dye.<b>(I ')</b> from 2 equivalents of pyridine derivative <b><u>1</u></b> and an equivalent of disulfide reagent comprising two leaving groups Gp, to lead to the dipyridinium disulfide salt <u><b>3</b></u> which can in turn condense with two equivalents of aryl compound with an aldehyde / thioaldehyde group <u><b>4</b></u> to lead to <b>(I ')</b>. <chemistry id="chem0046" num="0046"><img file="EP2004757B1_D0046.tif" /></chemistry>with Gp representing a nucleofuge leaving group, such as for example mesylate, tosylate, triflate or halide. Gp counterions^- compounds <b>(I '),</b> above can be replaced by counter-ions M ′ of other natures from methods known to those skilled in the art, in particular by ion-exchange resin.

0051The disymmetric disulfide dyes of formula <b>(I)</b> can be synthesized in one step by reacting an unprotected fluorescent thiol dye with a fluorescent thiol dye protected by Y 'to form the disulfide dye of formula <b>(I).</b><chemistry id="chem0047" num="0047"><img file="EP2004757B1_D0047.tif" /></chemistry>with R, R ', R ", R'", R_g, R '_g, R "_g, R '"_g, R_h, R '_h, R "_h, R "'_h, R_i, R '_i, R "_i, R "'_i, m, m ', p, p', q, q 'and M' are as defined above; Y 'represents a protective group of thiol function.

0052We can refer to the book <nplcit id="ncit0014" npl-type="b"><text>Advanced Organic Chemistry, "Reactions, Mechanisms and Structures", J. March, 4th Ed, John Willey &amp; Sons, 1992</text></nplcit> or <nplcit id="ncit0015" npl-type="s"><text>TW Greene "Protective Groups in Organic Synthesis"</text></nplcit>, to have more details on the operating conditions implemented for the processes mentioned above.

0053The thiol fluorescent dyes formed can be transformed into thiol-fluorescent dyes protected -SY 'by the protection of thiol -SH using the conventional protective groups. The thiol fluorescent dyes are metallized also using the conventional methods known to those skilled in the art such as those described in<nplcit id="ncit0016" npl-type="b"><text>Advanced Organic Chemistry, "Reactions, Mechanisms and Structures", J. March, 4th Ed, John Willey &amp; Sons, NY, 1992</text></nplcit>.

0054The protected thiol dyes can be deprotected by conventional means such as those described in the works. <nplcit id="ncit0017" npl-type="b"><text>"Protective Groups in Organic Synthesis", TW Greene, John Willey &amp; Sons ed., NY, 1981</text></nplcit> ; <nplcit id="ncit0018" npl-type="b"><text>"Protecting Groups", P. Kocienski, Thieme, 3rd ed., 2005</text></nplcit>.

0055The composition of the invention contains at least one fluorescent dye of formula <b>(I)</b> or <b>(II).</b> In addition to the presence of at least one fluorescent dye of formula <b>(I)</b> or <b>(II),</b> the composition of the invention may also contain a reducing agent.

0056This reducing agent can be chosen from thiols, for example cysteine, homocysteine, thiolactic acid, the salts of these thiols, phosphines, bisulfite, sulfites, thioglycolic acid, as well as its esters, in particular the glycerol monothioglycolate, and thioglycerol. This reducing agent can also be chosen from borohydrides and their derivatives, such as for example the salts of borohydride, cyanoborohydride, triacetoxyborohydride, trimethoxyborohydride: sodium salts, lithium, potassium, calcium, quaternary ammoniums (tetramethylammonium, tetraethylammonium, tetra n -butylammonium, benzyltriethylammonium); catechol-borane.

0057The dye composition useful in the invention generally contains an amount of fluorescent dye of formula (I) or (II) of between 0.001 and 50% relative to the total weight of the composition. Preferably, this amount is between 0.005 and 20% by weight and even more preferably between 0.01 and 5% by weight relative to the total weight of the composition.

0058The dye composition may also contain additional direct dyes. These direct dyes are, for example, chosen from neutral, acidic or cationic benzene nitro direct dyes, neutral azo, acidic or cationic direct dyes, tetraazapentamethine dyes, quinonic dyes and in particular neutral, acidic or cationic anthraquinone dyes, direct azine dyes , triarylmethane direct dyes, indoamine direct dyes and natural direct dyes.

0059Among the natural direct dyes, mention may be made of lawsone, juglone, alizarin, pure purine, carminic acid, kermesic acid, purpurogallin, protocatechaldehyde, indigo, isatin, curcumin, spinulosin, apigenidine. It is also possible to use the extracts or decoctions containing these natural dyes and in particular the poultices or extracts based on henna.

0060The dye composition may contain one or more oxidation bases and / or one or more couplers conventionally used for dyeing keratin fibers.

0061Among the oxidation bases, mention may be made of para-phenylenediamines, bis-phenylalkylenediamines, para-aminophenols, bis-para-aminophenols, ortho-aminophenols, heterocyclic bases and their addition salts

0062Among these couplers, mention may in particular be made of meta-phenylenediamines, meta-aminophenols, meta-diphenols, naphthalene couplers, heterocyclic couplers and their addition salts.

0063The coupler (s) are each generally present in an amount of between 0.001 and 10% by weight of the total weight of the dye composition, preferably between 0.005 and 6%.

0064The oxidation base (s) present in the dye composition are generally present each in an amount between 0.001 to 10% by weight of the total weight of the dye composition, preferably between 0.005 and 6% by weight.

0065In general, the addition salts of the oxidation bases and of the couplers which can be used in the context of the invention are in particular chosen from addition salts with an acid such as hydrochlorides, hydrobromides, sulfates, citrates, succinates, tartrates, lactates, tosylates, benzenesulfonates, phosphates and acetates and addition salts with a base such as alkali metal hydroxides such as soda, potash, ammonia, amines or alkanolamines.

0066The medium suitable for dyeing, also called dye support, is a cosmetic medium generally consisting of water or a mixture of water and at least one organic solvent. As organic solvent, mention may, for example, be made of lower C alkanols.₁-VS₄, such as ethanol and isopropanol; polyols and polyol ethers such as 2-butoxyethanol, propylene glycol, propylene glycol monomethyl ether, monoethyl ether and diethylene glycol monomethyl ether, as well as aromatic alcohols such as benzyl alcohol or phenoxyethanol, and mixtures thereof.

0067The solvents when they are present are preferably present in proportions preferably of between 1 and 40% by weight approximately relative to the total weight of the dye composition, and even more preferably between 5 and 30% by weight approximately.

0068According to a variant, the invention contains a reducing agent capable of reducing the disulfide bonds of the keratin and / or of the dye of formula <b>(I).</b> This reducing agent is as defined above.

0069The dye composition may also contain various adjuvants conventionally used in compositions for dyeing the hair, such as anionic, cationic, nonionic, amphoteric, zwitterionic surfactants or mixtures thereof, anionic, cationic, nonionic, amphoteric, zwitterionic polymers or their mixtures, mineral or organic thickening agents, and in particular associative anionic, cationic polymer thickeners, nonionic and amphoteric, antioxidant agents, penetration agents, sequestering agents, perfumes, buffers, dispersing agents, conditioning agents such as for example volatile or non-volatile silicones, modified or unmodified such as silicones amines, film-forming agents, ceramides, preserving agents, opacifying agents, conductive polymers.

0070The above adjuvants are generally present in an amount for each of them of between 0.01 and 20% by weight relative to the weight of the composition.

0071Of course, those skilled in the art will take care to choose this or these optional additional compounds in such a way that the advantageous properties intrinsically attached to the dye composition according to the invention are not, or not substantially, affected by the or the additions envisaged.

0072The pH of the dye composition is generally between 3 and 14 approximately, and preferably between 5 and 11 approximately. It can be adjusted to the desired value by means of acidifying or basifying agents usually used in dyeing keratin fibers or even using conventional buffer systems.

0073Among the acidifying agents, there may be mentioned, by way of example, mineral or organic acids such as hydrochloric acid, orthophosphoric acid, sulfuric acid, carboxylic acids such as acetic acid, tartaric acid, citric acid, lactic acid, sulfonic acids.

0074Among the basifying agents, there may be mentioned, by way of example, ammonia, alkali carbonates, alkanolamines such as mono-, di- and triethanolamines as well as their derivatives, sodium or potassium hydroxides and compounds of following formula (y):<chemistry id="chem0048" num="0048"><img file="EP2004757B1_D0048.tif" /></chemistry>in which W_at is a propylene residue optionally substituted by a hydroxy group or a C 1 alkyl radical₁-VS₄ ; R_a1, R_a2, R_a3 and R_a4, identical or different, represent a hydrogen atom, a C 1 alkyl radical₁-VS₄ or C hydroxyalkyl₁-VS₄.

0075The dye composition may be in various forms, such as in the form of a liquid, cream, gel, or in any other form suitable for dyeing keratin fibers, and in particular hair.

0076According to a particular embodiment in the process of the invention, a reducing agent can be applied as a pretreatment before the application of the composition containing at least one fluorescent dye of formula <b>(I)</b> or <b>(II).</b>

0077This reducing agent can be chosen from thiols, for example cysteine, homocysteine, thiolactic acid, the salts of these thiols, phosphines, bisulfite, sulfites, thioglycolic acid, as well as its esters, in particular the glycerol monothioglycolate, and thioglycerol. This reducing agent can also be chosen from borohydrides and their derivatives, such as for example the salts of borohydride, cyanoborohydride, triacetoxyborohydride, trimethoxyborohydride: sodium salts, lithium, potassium, calcium, quaternary ammoniums (tetramethylammonium, tetraethylammonium, tetra n -butylammonium, benzyltriethylammonium); catecholborane.

0078This pretreatment can be of short duration, in particular from 0.1 second to 30 minutes, preferably from 1 minute to 15 minutes with a reducing agent as mentioned above.

0079According to another method, the composition comprising at least one fluorescent dye of formula <b>(I)</b> or <b>(II)</b> also contains at least one reducing agent as defined above. This composition is then applied to the hair.

0080When the thiol fluorescent dye of formula <b>(II)</b> includes a group Y protecting the thiol function, the process of the invention can be preceded by a deprotection step aimed at restoring <i>in-situ</i> the SH function.

0081For example, it is possible to unprotect the SY function with Y protective group by adjusting the pH as follows:<tables id="tabl0002" num="0002"><table frame="all"><tgroup cols="2"><colspec colnum="1" colname="col1" colwidth="123mm" /><colspec colnum="2" colname="col2" colwidth="23mm" /><thead><row><entry valign="top">Y: protecting group</entry><entry align="center" valign="top">protection</entry></row></thead><tbody><row><entry /><entry /></row><row><entry>alkylcarbonyl,</entry><entry align="center">pH> 9</entry></row><row><entry>arylcarbonyl,</entry><entry align="center">pH> 9</entry></row><row><entry>alkoxycarbonyl,</entry><entry align="center">pH> 9</entry></row><row><entry>aryloxycarbonyl,</entry><entry align="center">pH> 9</entry></row><row><entry>arylalkoxycarbonyl</entry><entry align="center">pH> 9</entry></row><row><entry>(di) (alkyl) aminocarbonyl,</entry><entry align="center">pH> 9</entry></row><row><entry>(alkyl) arylaminocarbonyl</entry><entry align="center">pH> 9</entry></row><row><entry>optionally substituted aryl such as phenyl,</entry><entry align="center">pH> 9</entry></row><row><entry>5-, 6- or 7-membered monocyclic heteroaryl such as oxazolium;</entry><entry align="center">pH> 9</entry></row><row><entry>8 to 11 membered bicyclic heteroaryl such as benzoimidazolium, or benzoxazolium</entry><entry align="center">pH> 9</entry></row></tbody></tgroup></table></tables>

0082The deprotection step can also be carried out during a hair pretreatment step such as, for example, the reducing hair pretreatment.

0083According to one variant, the reducing agent is added to the dye composition containing at least one fluorescent dye of formula <b>(I)</b> or <b>(II)</b> at the time of employment.

0084According to another method, the composition comprising at least one fluorescent dye of formula <b>(I)</b> or <b>(II)</b> also contains at least one reducing agent as defined above. This composition is then applied to the hair.

0085According to another variant, the reducing agent is applied in post-treatment, after the application of the composition containing at least one fluorescent dye of formula <b>(I)</b> or <b>(II).</b> The duration of the post-treatment with the reducing agent can be short, for example from 0.1 second to 30 minutes, preferably from 1 minute to 15 minutes, with a reducing agent as described above. According to a particular embodiment, the reducing agent is an agent of the thiol or borohydride type as described above.

0086A particular embodiment of the invention relates to a method in which the fluorescent dye of formula <b>(I)</b> or <b>(II)</b> can be applied directly to hair without reducing agents, free from reducing pre- or post-treatment.

0087A treatment with an oxidizing agent may possibly be combined. Any type of conventional oxidizing agent in the field can be used. Thus, it can be chosen from hydrogen peroxide, urea peroxide, alkali metal bromates, persalts such as perborates and persulfates, as well as the enzymes among which mention may be made of peroxidases, oxido- 2 electron reductases such as uricases and 4 electron oxygenases such as laccases. The use of hydrogen peroxide is particularly preferred.

0088This oxidizing agent can be applied to the fibers before or after the application of the composition containing at least one fluorescent dye of formula <b>(1)</b> or <b>(II).</b>

0089The application of the dye composition according to the invention is generally carried out at room temperature. It can however be carried out at temperatures varying from 20 to 180 ° C.

0090The invention also relates to a device with several compartments or "kit" for dyeing in which a first compartment contains a dye composition comprising at least one fluorescent dye of formula <b>(I)</b> or <b>(II)</b> and a second compartment contains a reducing agent capable of reducing the disulfide functions of keratin materials.

0091One of these compartments may also contain one or more other dyes of the direct dye or oxidation dye type.

0092It also relates to a device with several compartments in which a first compartment contains a dye composition comprising at least one fluorescent dye of formula <b>(I)</b> or <b>(II);</b> a second compartment contains a reducing agent capable of reducing the disulfide bond of keratin materials; a third compartment contains an oxidizing agent.

0093Alternatively, the dyeing device contains a first compartment containing a dye composition which comprises at least one protected thiol fluorescent dye of formula <b>(II)</b> and a second compartment containing an agent capable of deprotecting the protected thiol to release the thiol.

0094Each of the devices mentioned above can be equipped with a means enabling the desired mixture to be delivered to the hair, for example such as the devices described in the patent. <patcit id="pcit0007" dnum="FR2586913"><text>FR2 586 913</text></patcit>.

0095The examples which follow serve to illustrate the invention without, however, being limiting in nature. The thiol fluorescent dyes of the examples below were fully characterized by conventional spectroscopic and spectrometric methods.

EXAMPLES

EXAMPLES OF SYNTHESIS

<u>Example 1:</u> Synthesis of 1,1 'dimethane sulfonate - (disulfanedlyldiéthane-2,1-diyl) bis [4 - ((E) -2- (4- [bis (2-hydroxyethyl) amino] phenyl} vinyl) pyridinium] [1 ]

0096<chemistry id="chem0049" num="0049"><img file="EP2004757B1_D0049.tif" /></chemistry>

Synthesis diagram

0097<chemistry id="chem0050" num="0050"><img file="EP2004757B1_D0050.tif" /></chemistry>

Procedure

Step 1: Synthesis of disulfanediyldiethane-2,1-diyl dimethanesulfonate

009810 g of 2,2'-dithiodiethanol and 14.44 g of triethylamine (TEA) are diluted in 100 ml of AcOEt. At 0 ° C, 16.35 g of methanesulfonyl chloride diluted in 35 ml of AcOEt are added dropwise to the reaction medium with rapid stirring. 7.22 g of TEA are introduced, the stirring is continued at room temperature for 4 h 30. 8.2 g of methanesulfonyl chloride are added dropwise at 15 ° C., then the stirring is maintained at room temperature for 5 p.m. The precipitate is filtered and washed with 3 times 50 ml of AcOEt. The organic phases are extracted with 100 mL of ice water; 100 mL of water, 3 times 50 mL of saturated NaHCO solution₃, with 2 times 20 mL of saturated NaCl, then dried over Na₂SO₄ anhydrous. The AcOEt is evaporated, and 17.49 g of pale yellow translucent oil are collected. Analysis indicates that the product is compliant.

Step 2: Synthesis of 1,1 'dimethanesulfonate - (disulfanediyldiethane-2,1-diyl) bis (4-methylpyridinium)

00993.51 g of 4 picoline and 5 g of disulfanediyldiethane-2,1-diyl dimethanesulfonate are diluted in 5 mL of N-methylpyrrolidinone (NMP) then heated to 80 ° C with stirring for 2 h. Stirring is maintained at room temperature for 17 h. The reaction medium is completed with 50 ml of AcOEt, then filtered, washed with 3 times 100 ml of AcOEt, and dried under vacuum in the presence of P₂O₅. 7.29 g of brown powder are collected. Analyzes indicate that the product is compliant and pure. NMR¹H (400 MHz, DMSO-d₆) 2.31 (s, 6 H), 2.62 (s, 6 H), 3.40 (t, 4 H), 4.83 (t, 4 H), 8.01 (d, 4 H), 8.91 (d, 4 H).

Step 3: Synthesis of 1,1 'dimethane sulfonate - (disulfanediyldiethane-2,1-diyl) bis [4 - ((E) -2- {4- [bis (2-hydroxyethyl) amino] phenyl} vinyl) pyridinium ] [1]

01004.32 g of 4- [bis- (2-hydroxy-ethyl) -amino] -benzaldehyde, 10 ml of iProH, and 1.69 ml of pyrrolidine are mixed with stirring for 10 minutes. 1.18 ml of acetic acid are added and the mixture is stirred at room temperature for 20 minutes. 5 g of 1,1 'dimethanesulfonate - (disulfanediyldiethane-2,1-diyl) bis (4-methylpyridinium) suspended in 7 mL of iProH and 2 mL of methanol are added. The reaction mixture is kept stirred for 24 h at room temperature. The precipitate obtained is filtered, washed with 100 ml of acetone and then dried. 8.56 g of powder are collected. Analyzes indicate that the product is compliant and pure. NMR¹H (400 MHz, MeOH-d4) 2.71 (s, 6 H), 3.35 (t, 4 H), 3.64 (t, 8 H), 3.76 (t, 8 H), 4.74 (t, 4 H), 6.83 (d, 4 H), 7.04 (d, 2 H), 7.58 (d, 4 H), 7.81 (d, 2 H), 7.96 (d, 4 H), 8.56 (d, 4 H).

<u>Example 2:</u> Synthesis of 1,1 '- (disulfanediyldiethane-2,1-diyl) bis [4 - ((E) -2- {4- [ethyl (2-hydroxyethyl) amino] -2-methyl) phenyl} -1 dibromide -methylvinyl) pyridinium] [2]

0101<chemistry id="chem0051" num="0051"><img file="EP2004757B1_D0051.tif" /></chemistry>

Synthesis diagram

0102<chemistry id="chem0052" num="0052"><img file="EP2004757B1_D0052.tif" /></chemistry>

Procedure

Step 1: Synthesis of 1,1 '- (disulfanedlyldiéthane-2,1-diyl) bis (4-ethylpyridinium) dibromide

010312., 9 g of 4-ethyl-pyridine dissolved in 4 ml of NMP and 15 ml of acetonitrile (ACN) are stirred and heated to 80 ° C. 15 g of 1-Bromo-2- (2-bromo-ethyldisulfanyl) -ethane diluted in 10 ml of ACN are added dropwise to the medium for 30 minutes. The reaction mixture is stirred and heated to reflux for 4 h, then at room temperature for 17 h. To the green solid obtained, 200 ml of acetone are added, the solid is broken, then filtered, washed with 50 ml of acetone, then dried. 23.32 g of green powder are collected. Analysis indicates that the product is compliant.

Step 2: Synthesis of 1,1 '- (disulfanediyldiethane-2,1-diyl) bis [4 - ((E) -2- {4- (ethyl (2-hydroxyethyl) amino] -2) methylphenyl} - dibromide 1-methylvinyl) pyridinium] [2]

01045 g of 4- [ethyl- (2-hydroxy-ethyl) -amino] -2-methyl-benzaldehyde, 10 ml of iProH, and 1.74 ml of pyrrolidine are mixed with stirring for 10 min. 1.21 ml of acetic acid are added and the mixture is stirred at room temperature for 20 min. 5 g of 1,1 '- (disulfanediyldiethane-2,1-diyl) bis (4-ethylpyridinium) dibromide suspended in 7 ml of iProH and 5 ml of methanol are added. The reaction mixture is kept stirred for 1 week at room temperature. The reaction mixture is stored at room temperature for 4 weeks. The reaction mixture is concentrated, the residue is extracted with a mixture H₂O / CH₂Cl₂, then the expected product is extracted with butanol, the organic phase is concentrated, and the residue is taken up in ethyl acetate. The precipitate obtained is filtered and then dried. 810 mg of powder are collected. Analysis indicates that the product is compliant.

<u>Example 3:</u> Synthesis of 1,1 'dimethane sulfonate - (disulfanediyldiethane-2,1-diyl) bis [4 - ((E) -2- {4 - [[3- (dimethylamino) propyl] (methyl) amino] phenyl} vinyl ) -pyridinium] [3]

0105<chemistry id="chem0053" num="0053"><img file="EP2004757B1_D0053.tif" /></chemistry>

Synthesis diagram

0106<chemistry id="chem0054" num="0054"><img file="EP2004757B1_D0054.tif" /></chemistry>

Procedure

Step 1: Synthesis of 4 - [[3- (dimethylamino) propyl] (methyl) amino] benzaldehyde

010710 g of 4-fluorobenzaldehyde, 12 g of K₂CO₃, 20 mL of NMP are stirred and heated to 50 ° C. 13 mL of NNN'-trimethyl-1.3-propanediamine are added dropwise to the medium, maintained under stirring and heated at 80 ° C for 10 h. After the reaction medium has cooled to room temperature, 100 ml of acetone are added. The precipitate obtained is filtered, the filtrate is evaporated to dryness and then dried. 21.85 g of powder are collected. Analysis indicates that the product is compliant.

Step 2: Synthesis of 1,1 '- di methane sulfonate (disulfanediyldiethane-2,1-diyl) bis [4 - ((E) -2- {4 - [[3- (dimethylamino) propyl] (methyl) amino ] phenyl} vinyl) -pyridinium] [3]

01082 g of 4 - [(3-dimethylamino-propyl) -methyl-amino] -benzaldehyde dissolved in 5 ml of iProH, to which 585 μL of pyrrolidine are added are stirred at room temperature for 10 minutes. 408 μL of acetic acid are added to the reaction medium maintained with stirring at room temperature for 20 minutes. 1.71 g of 1.1 'di methanesulfonate - (disulfanediyldiethane-2,1-diyl) bis (4-methyl-pyridinium) previously dissolved in 3 ml of iProH and 1 ml of methanol are introduced into the medium, stirred at 20 ° C for 4 days. 50 mL of diisopropyl ether are added to the cooled reaction mixture via a dry ice and acetone bath. The precipitate obtained is filtered and then dried. 2.21 g of purple powder are collected. Analysis indicates that the product is compliant. NMR¹H (400 MHz, MeOH-d4) 1.84 (m 4 H), 2.34 (s, 12 H), 2.48 (t, 4H), 2.71 (s, 6 H), 3.06 (s, 6H), 3.36 (t, 4H), 3.50 (t, 4 H), 4.75 (t, 4 H), 6.79 (d, 4 H), 7.07 (d, 2 H), 7.60 (d, 4 H), 7.84 (d, 2 H) , 7.98 (d, 4 H), 8.57 (d, 4 H).

<u>Example 4:</u> Synthesis of the 1,1 '- (disulfanediyldiethane-2,1-diyl) bis {2 - [(E) -2- (4- {methyl [3- (trimethylammonio) propyl] amino} phenyl) vinyl] pyridinium} salt [4]

0109<chemistry id="chem0055" num="0055"><img file="EP2004757B1_D0055.tif" /></chemistry>

Synthesis diagram

0110<chemistry id="chem0056" num="0056"><img file="EP2004757B1_D0056.tif" /></chemistry>

Procedure

Step 1: Synthesis of 1,1 '- (disulfanediyldiethane-2,1-diyl) bis (2-methyl-pyridinium) dibromide

0111A mixture of 56 g of 1-bromo-2 - [(2-bromoethyl) disulfanyl] ethane and 15 mL of <i>NOT-</i>Methylpyrrolidone (NMP) is poured dropwise onto 35 g of 2-picoline with stirring, at 80 ° C. The mixture (white suspension) is kept stirred for 30 min at 80 ° C., 100 ml of ACN are added, stirring is maintained at 80 ° C. for 90 min. After cooling, the solid obtained is filtered, washed with 100 ml of ACN and then dried. 56.2 g of brown powder are collected. 45 g of this powder are suspended in 300 ml of iProH, at reflux. Once the temperature has dropped to 40 ° C., the solid is filtered, washed with 3 times 100 ml of iProH and dried under vacuum. Light beige product, 40.56 g. Analysis in accordance with the expected structure.

Step 2: Synthesis of 3 - [(4-formylphenyl) (methyl) amino] -N, N, N-trimethylpropan-1-aminium methyl sulfate

01125 g of - [[3- (dimethylamino) propyl] (methyl) amino] benzaldehyde are diluted in 15 ml of dichloromethane. 2.36 mL of dimethyl sulfate diluted in 10 mL of dichloromethane are gradually added. The mixture is heated at reflux for 4 h then cooled to room temperature and poured onto 100 ml of ethyl acetate. The brown oil formed is decanted, washed with 100 ml of AcOEt, taken up in 200 ml of methanol and concentrated in vacuo. It is then dissolved in a saturated solution of baking soda and sodium chloride and extracted with butanol. The butanol phase is concentrated under vacuum, dried under vacuum in the presence of P₂O₅, then the product is used for the next step.

Step 3: Synthesis of the 1,1 '- (disulfanediyldiethane-2,1-diyl) bis {2 - [(E) -2- (4- {methyl [3- (trimethylammonio) propyl] amino} phenyl) vinyl salt ] pyridinium} [4]

01130.62 g of 3 - [(4-formylphenyl) (methyl) amino] sulphate -N, N, N, trimethylpropan-1-aminium methyl dissolved in 2 ml of iProH and 3 ml of methanol to which 0, 15 mL of pyrrolidine are stirred at room temperature for 10 minutes. 0.11 ml of acetic acid is added to the reaction medium maintained under stirring at room temperature for 20 minutes. 0.41 g of 1.1 'dibromide - (disulfanediyldiethane-2,1-diyl) bis (2-methyl-pyridinium) previously dissolved in 2 ml of iProH and 2 ml of methanol are introduced into the medium, stirred at 20 ° C for 17 h. The analyzes show the expected presence of the product.

<u>Example 5:</u> Synthesis of 4 - ((E) -2- {4- [bis (2-hydroxyethyl) amino] -phenyl} vinyl) -1- (2-sulfanylethyl) pyridinium methanesulfonate [5]

0114<chemistry id="chem0057" num="0057"><img file="EP2004757B1_D0057.tif" /></chemistry>

Synthesis diagram

0115<chemistry id="chem0058" num="0058"><img file="EP2004757B1_D0058.tif" /></chemistry>

Procedure

Synthesis of the salt of 4 - ((E) -2- {4- [bis (2-hydroxyethyl ethyl) amino] phenyl} -vinyl) -1- (2-sulfanylethyl) pyridinium [5]

011688 mg of compound [1] are dissolved in 10 mL of water / ethanol mixture (1/1); 60 mg (2 eq.) Of 3- [bis (2-carboxy-ethyl) phosphino] propanoic acid hydrochloride hydrate in solution in 1 ml of water and 21 mg (4 eq) of sodium bicarbonate in solution in 1 mL of water are added to the mixture. After 30 minutes of stirring at 40 ° C under an inert atmosphere, the analyzes indicate that the mixture contains most of the expected product [5].<ul id="ul0010" list-style="none" compact="compact"><li>LC-MS analysis: LC-DAD (400-700 nm)</li><li>Column: Waters XTerra MS C18 5µm (4.6 x 50) mm</li><li>Mobile phase: A: Water + formic acid 0.1% / B: acetonitrile</li><li>Linear gradient: T (min) A% / B%: 0 min 95/5; 8 min 0/100</li><li>Flow rate: 1 mL / min.</li><li>Detection: UV Diode array λ = 400-700nm</li></ul><ul id="ul0011" list-style="none" compact="compact"><li>Retention time t = 3.3 min</li><li>Relative purity> 90%</li><li>MS (ESI +) m / z = 345 corresponds to the mass peak of the monocation of the expected product [5]</li></ul>

COLORING EXAMPLES

Example 1 - staining process with compounds [1] to [4]

Preparation of composition A

0117<tables id="tabl0003" num="0003"><table frame="all"><tgroup cols="2"><colspec colnum="1" colname="col1" colwidth="73mm" /><colspec colnum="2" colname="col2" colwidth="20mm" /><tbody><row><entry>Disulfide dye from [1] to [4]</entry><entry align="right">10^-3 mol%</entry></row><row><entry>Benzyl alcohol</entry><entry align="right">4 g</entry></row><row><entry>Polyethylene glycol 6OE</entry><entry align="right">6 g</entry></row><row><entry>Hydroxyethylcellulose</entry><entry align="right">0.7 g</entry></row><row><entry>Alkylpolyglucoside in aqueous solution at 65% MA</entry><entry align="right">4.5g</entry></row><row><entry>Demineralized Water</entry><entry align="right">qs 100g</entry></row></tbody></tgroup></table></tables>

Preparation of a composition B

0118<tables id="tabl0004" num="0004"><table frame="all"><tgroup cols="2"><colspec colnum="1" colname="col1" colwidth="36mm" /><colspec colnum="2" colname="col2" colwidth="20mm" /><tbody><row><entry>Thioglycolic acid</entry><entry align="right">1 M</entry></row><row><entry>Sodium hydroxide</entry><entry align="right">qs pH 8.5</entry></row><row><entry>Demineralized Water</entry><entry align="right">qs 100g</entry></row></tbody></tgroup></table></tables>

0119At the time of use, compositions A (9 mL) and B (1 mL) are mixed, then the mixture obtained is applied to a lock of 1 g of dark hair (pitch 4) for 30 minutes at room temperature (the wicks are turned over and re-impregnated after 15 minutes).

0120After rinsing with running water and drying, a lightening of the hair thus treated is observed: the lock of pitch 4 has become visually clearer than untreated control locks.

Example 2 - staining process with compound [5]

012110 mL of fresh solution of compound [5] of the synthesis example are applied to a lock of 1 g of hair, tone height 4, placed at the bottom of the same bowl for 30 minutes at room temperature (the locks are turned over and impregnated after 15 minutes). The locks are then rinsed with running water and dried. After coloring the wick of pitch of tone 4 became visually lighter than untreated control wicks.

Remanence towards successive shampoos:

0122The locks thus treated are divided into two, one half is subjected to 5 successive shampoos according to a cycle which comprises wetting the locks with water, washing with a conventional shampoo, rinsing with water followed by drying.

Visual observations

0123During shampooing, there is no visible bleeding, the foam of the shampoos and the rinsing waters are not colored

0124The color observed on the locks is preserved and the lightening effect remains visible on the hair thus treated.

Results in the L system

*

at

*

b

*

:

0125The color of the locks before and after the 5 washes was evaluated in the L * a * b * system using a CM 2600D MINOLTA® spectrophotometer (Illuminant D65).

0126In this system L * a * b *, L * represents the brightness, a * indicates the axis of color green / red and b * the axis of color blue / yellow. The higher the value of L, the lighter or less intense the color. Conversely, the lower the value of L, the darker or very intense the color. The higher the value of a * the more the shade is red and the higher the value of b * the more the shade is yellow.

0127The variation in coloring between the strands of HT4 hair, colored and washed is measured by (ΔE) according to the following equation: <maths id="math0001"><math display="block"><mi mathvariant="normal">ΔE</mi><mo mathvariant="normal">=</mo><msqrt><msup><mfenced><mi mathvariant="normal">L</mi><mo mathvariant="normal">*</mo><mo mathvariant="normal">-</mo><msup><msub><mi mathvariant="normal">L</mi><mi mathvariant="normal">o</mi></msub><mo mathvariant="normal">*</mo></msup></mfenced><mn mathvariant="normal">2</mn></msup><mo mathvariant="normal">+</mo><msup><mfenced><msup><mi mathvariant="normal">at</mi><mo mathvariant="normal">*</mo></msup><mo mathvariant="normal">-</mo><msup><msub><mi mathvariant="normal">at</mi><mi mathvariant="normal">o</mi></msub><mo mathvariant="normal">*</mo></msup></mfenced><mn mathvariant="normal">2</mn></msup><mo mathvariant="normal">+</mo><msup><mfenced><msup><mi mathvariant="normal">b</mi><mo mathvariant="normal">*</mo></msup><mo mathvariant="normal">-</mo><msup><msub><mi mathvariant="normal">b</mi><mi mathvariant="normal">o</mi></msub><mo mathvariant="normal">*</mo></msup></mfenced><mn mathvariant="normal">2</mn></msup></msqrt></math><img file="EP2004757B1_D0059.tif" /></maths>

0128In this equation, L *, a * and b * represent the values ​​measured before coloring and L₀*, at₀* and B₀* represent the values ​​measured before coloring (or shampooing).

0129The greater the value of ΔE, the greater the difference in color between the HT4 locks and the colored locks.<tables id="tabl0005" num="0005"><table frame="all"><tgroup cols="2"><colspec colnum="1" colname="col1" colwidth="120mm" /><colspec colnum="2" colname="col2" colwidth="12mm" /><thead><row><entry valign="top"><b>Treatment with fluorescent dye on HT4 wicks</b></entry><entry align="center" valign="top"><b>ΔE</b></entry></row></thead><tbody><row><entry /><entry align="center" /></row><row><entry>After application of compound 1 according to the invention</entry><entry align="center">8,38</entry></row><row><entry>After application of compound 1 according to the invention and after 5 successive shampoos</entry><entry align="center">8,66</entry></row><row><entry /><entry align="center" /></row><row><entry>After application of compound 2 according to the invention</entry><entry align="center">2,71</entry></row><row><entry>After application of compound 2 according to the invention and after 5 successive shampoos</entry><entry align="center">2,84</entry></row><row><entry /><entry align="center" /></row><row><entry>After application of compound 3 according to the invention</entry><entry align="center">9,62</entry></row><row><entry>After application of compound 3 according to the invention and after 5 successive shampoos</entry><entry align="center">9,88</entry></row><row><entry /><entry align="center" /></row><row><entry>After application of compound 5 according to the invention</entry><entry align="center">5,27</entry></row><row><entry>After application of compound 5 according to the invention and after 5 successive shampoos</entry><entry align="center">5,25</entry></row></tbody></tgroup></table></tables>

The results in the table above show that the coloring changes very little after 5 shampoos. Thus the coloring and the lightening effect on the hair remain almost unchanged, which shows very good resistance to shampooing of the dyes of the invention.

Reflectance Results:

0130The lightening performance of the compositions according to the invention and their persistence with respect to successive shampoos were expressed as a function of the reflectance of the hair. These reflectances are compared to the reflectance of a lock of untreated hair of tone height HT4.

0131The reflectance is measured using a KONIKA-MINOLTA® spectrophotocolorimeter, CM 2600d and after irradiation of the hair with visible light in the wavelength range from 400 to 700 nanometers.<tables id="tabl0006" num="0006"><img file="EP2004757B1_D0060.tif" /></tables><tables id="tabl0007" num="0007"><img file="EP2004757B1_D0061.tif" /></tables><tables id="tabl0008" num="0008"><img file="EP2004757B1_D0062.tif" /></tables>

0132It is noted first of all that the reflectance of a lock of hair treated with a composition according to the invention is higher than that of untreated hair. The treated locks therefore appear lighter.

0133In addition, the results show that the reflectance of the strands of tone height 4 treated with the compositions of the invention changes very shortly after 5 shampoos. Thus the coloring and the lightening effect on the hair remain almost unchanged, which shows very good resistance to shampooing of the dyes of the invention.