Dyeing composition containing a thiol/disulphide fluorescent colorant having an external cationic charge and an interrupted alkylene chain, and method for lightening keratin materials using said colorant

0001The invention relates to the coloring of keratin fibers using fluorescent dyes thiols / pyridinium disulphides with an external cationic charge and interrupted alkylene chain.

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 triarylmethane 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 method 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 dyeing 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 an appropriate cosmetic medium, at least one fluorescent thiol pyridinium dye with an external cationic charge chosen from the following dyes of formula (I) or (II):<chemistry id="chem0001" num="0001"><img file="EP2004755B1_D0001.tif" /></chemistry>their organic or mineral acid salts, optical isomers, geometric isomers, and solvates such as hydrates; formula (I) in which:<ul id="ul0001" list-style="none" compact="compact"><li>➢ R_at and R '_at, identical or different, represent an aryl group (C₁-VS₄) alkyl or a group (C₁-VS₆) alkyl optionally substituted by a hydroxy or amino group, C₁-VS₄ alkylamino, (C₁-VS₄) dialkylamino, said alkyl radicals being able to form, with the nitrogen atom which carries them, a heterocycle comprising from 5 to 7 members, optionally comprising another heteroatom different or not from nitrogen; preferably R_at and R '_at represent a group (C₁-VS₃) alkyl optionally substituted by a hydroxy group, or a benzyl group;</li><li>➢ R_b and R '_b, identical or different, represent a hydrogen atom, an aryl group (C₁-VS₄) alkyl or a group (C₁-VS₆) optionally substituted alkyl; including R_b and R '_b represent a hydrogen atom or a group (C₁-VS₃) alkyl or benzyl;</li><li>➢ R_g, R '_g, R "_g and R "'_g, identical or different, represent a hydrogen atom, an amino group, (C₁-VS₄) alkylamino, (C₁-VS₄) dialkylamino,, trifluoromethyl, an acylamino radical, (C₁-VS₄) alkoxy (C₁-VS₄) alkylcarbonyloxy, (C₁-VS₄) alkoxycarbonyl, (C₁-VS₄) alkylcarbonylamino, (C₁-VS₄) alkylsulfonylamino, a radical (C₁-VS₃) alkyl;</li><li>➢ R_h, R '_h, R "_h and R "'_h, identical or different, represent a hydrogen atom, a halogen atom, a dialkylamino group (C₁-VS₄), (VS₁-VS₄) alkylcarbonylamino, an acylamino radical, (C₁-VS₄) alkylsulfonylamino, or a radical (C₁-VS₄) alkyl; particularly R_h, R '_h, R "_h and R "'_h, represent a hydrogen atom, or a group (C₁-VS₃) alkyl;</li><li>➢ or two R groups_g and R '_g ; R "_g and R "'_g; R_h, and R '_h ; R "_h and R "'_h carried by two adjacent carbon atoms, together form a benzo, indeno ring, a fused heterocycloalkyl or fused heteroaryl group; the benzo, indeno, heterocycloalkyl or heteroaryl ring being optionally substituted by a halogen atom, an amino group, (C₁-C4) alkylamino, (C₁-VS₄) dialkylamino, cyano, carboxy, hydroxy, trifluoromethyl, acylamino, C alkoxy₁-VS₄, (poly) hydroxyalkoxy in C₂-VS₄, (VS₁-VS₄) alkylcarbonyloxy (C₁-VS₄) alkoxycarbonyl, (C₁-VS₄) alkylcarbonylamino, an acylamino, carbamoyl radical, (C₁-VS₄) alkylsulfonyl-amino, an aminosulfonyl radical, or a (C₁-VS₁₆) alkyl optionally substituted by a group chosen from (C₁-VS₁₂) alkoxy, hydroxy, cyano, carboxy, amino, (C₁-VS₄) alkylamino and (C₁-VS₄) dialkylamino, or else 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 and R '_g; R "_g and R "'₉ together form a benzo group;</li><li>➢ R_i, R '_i, R "_j and R "'_i, identical or different, represent a hydrogen atom, or a group (C₁-VS₄) alkyl; particularly a hydrogen atom;</li><li>➢ R₁, R₂, R₃, R₄, R '₁, R '₂, R '₃ and R '₄, identical or different, represent a hydrogen atom or a group (C₁-VS₄) alkyl, (C₁-VS₁₂) alkoxy, hydroxy, cyano, carboxy, (di) (C₁-VS₄) (alkyl) amino, said alkyl radicals being able to form, with the nitrogen atom which carries them, a heterocycle comprising from 5 to 7 members, optionally comprising another heteroatom different or not from nitrogen; including R₁, R₂, R₃ and R₄ are hydrogen atoms or a group (di) (C₁-VS₄) (alkyl) amino, preferably R₁, R₂, R '₁ and R '₂ represent a hydrogen atom and R₃, R₄, R '₃ or R '₄ represent a hydrogen atom or a group (di) (C₁-VS₄) (alkyl) amino; the group (di) (C₁-VS₄) (alkyl) amino found particularly at α of the T bond_at or T_b when n or n 'is greater than 1; particularly R₃, R₄, R '₃ and R '₄, represent a hydrogen atom or an amino group and only one of the R groups₃, R₄ and / or only one of the groups R '₃ and R '₄ can only represent an amino group, said amino group preferably being located at α of the T bond_at and / or T_b when n or n 'is greater than 1; more particularly R₁, R₂, R₃, R₄, R '₁, R '₂, R '₃ and R '₄, represent a hydrogen atom;</li><li>➢ T_at and T_b, identical or different, represent the combination of radicals chosen from -SO₂-, -O-, -S-, -N (R) -, -CO-, with R, represents a hydrogen atom, a C 1 alkyl radical₁-VS₄, C-hydroxyalkyl₁-VS₄; or an aryl (C₁-VS₄) alkyl, in particular represent a group chosen from -C (O) -N (R) -, -N (R) -C (O) -;</li><li>➢ m, m ', n and n', identical or different, represent an integer inclusive between 0 and 6 with m + n and m '+ n', identical or different, represent an integer inclusive between 1 and 10; particularly the sum m + n = m '+ n' is an integer inclusive between 4 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>it being understood that when the compound of formula (I) or (II) contains other cationic parts, it is found associated with one or more anionic counterions making it possible to achieve the electroneutrality of the formula (I) or (II ).

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

0017A subject of the invention is also new fluorescent dyes of formula (I) or (II) as defined above.

0018The dyeing process according to the invention makes it possible to visibly color dark keratin materials, in particular dark human keratin fibers, in particular dark hair.

0019In addition, the process of the invention makes it possible to obtain a coloration of keratin materials, in particular human keratin fibers, in particular the hair, without degrading said material, which is persistent with regard to shampoos, common attacks (sun, perspiration ), and other hair treatments. The method 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.

0020For the purposes of the invention, the term “dark keratinous material” is understood to mean that which has a luminescence L * encrypted in the CIEL system * 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.

0021For 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).

0022The lightening of the hair is evaluated by the variation in "pitch" before and after application of the compound of formula (I) or (II).

0023The 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>“Science of hair treatments” by ZVIAK Charters 1988, Ed. Masson, p. 215 and 278</text></nplcit>.

0024The 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.

0025An artificially colored hair is a hair whose color has been modified by a coloring treatment, for example coloring with direct dyes or oxidation dyes.

0026Preferably, the composition must, after application to hair, for example brown hair, lead to the results below.<ul id="ul0002" 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>

0027Preferably, 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 the wavelength range from 550 to 620 nanometers.

0028Within the meaning of the present invention, and unless a different indication is given:<ul id="ul0003" list-style="none" compact="compact"><li>the “aryl” or “heteroaryl” radicals can be substituted by at least one substituent carried by a carbon atom, chosen from:<ul id="ul0004" list-style="bullet" compact="compact"><li>a C 1 alkyl radical₁-VS₁₆, preferably in C₁-VS₆ ;</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>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</li></ol></li><li>an acylamino radical (-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>a carbamoyie radical ((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>an alkylsulfonylamino radical (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 ;</li><li>an aminosulfonyl radical ((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;<ul id="ul0005" list-style="dash" compact="compact"><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:</li></ul></li><li>hydroxy,</li><li>C alkyl₁-VS₄,</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 or a C 1 alkyl radical₁-VS₄ and the radical R is a hydrogen atom, a C 1 alkyl radical₁-VS₂, or amino substituted by two identical or different C alkyl groups₁-VS₄ 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><li>RCO-O- in which the radical R is a C 1 alkyl radical₁-VS₄, amino substituted by two identical or different C alkyl groups₁-VS₄, 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><li>RO-CO- in which the radical R is a C 1 alkyl radical₁-VS₄, amino substituted by two identical or different C alkyl groups₁-VS₄ 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;<ul id="ul0006" list-style="dash" compact="compact"><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 and sulfur atoms 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 radical” is a mono or polycyclic nonaromatic radical, condensed or not, containing from 5 to 22 links, comprising from 1 to 6 heteroatoms chosen from the nitrogen, oxygen, sulfur and selenium atom;</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 i) hydroxy, ii) alkoxy radicals₁-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 heterocycle comprising from 5 to 7 members, optionally comprising another heteroatom different or not from nitrogen;</li><li>an "alkoxy radical" is an alkyl-oxy or alkyl-O- radical for which the alkyl radical is a linear or branched C hydrocarbon radical₁-VS₁₆ preferably in C₁-VS₈ ;</li><li>an "alkylthio radical" is an alkyl-S- radical for which the alkyl radical is a hydrocarbon radical, linear or branched, at C₁-VS₁₆ preferably in C₁-VS₈ ;</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: Ar-S (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 a 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></li></ul></li></ul>

0029The fluorescent dyes of formula (I) or (II) are compounds capable of absorbing in UV or visible radiation at a wavelength λ_abs between 250 and 700 nm and capable of re-emitting in the visible range at an emission wavelength λ_em between 400 and 700 nm.

0030Preferably the fluorescent compounds of formula (I) or (II) are dyes capable of absorbing in the visible, λ_abs between 400 and 700 nm, and reemitting in the visible, λ_em between 500 and 650 nm. More particularly the fluorescent dyes are dyes capable of absorbing at a wavelength λ_abs between 420 nm and 550 nm and re-emitting in the visible at a wavelength λ_em between 550 and 620 nm.

0031A particular mode concerns the fluorescent dyes of formula (I) or (II) with SY function where Y represents a hydrogen atom, or an alkali metal. Advantageously Y represents a hydrogen atom.

0032The fluorescent compounds of the invention of formula (II) 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.

0033In accordance with another particular embodiment of the invention, in the above formula (II), 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>.

0034Particularly 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) alkoxycarbonyl;</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="chem0002" num="0002"><img file="EP2004755B1_D0002.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 5, 6 or 7-membered saturated or partially saturated monocyclic group 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="chem0003" num="0003"><img file="EP2004755B1_D0003.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;<ul id="ul0008" list-style="none" compact="compact"><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, or (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="ul0009" 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></li></ul>

0035According to a particular embodiment, the protected thiol fluorescent dyes of formula (II) comprise a group Y i) monocyclic heteroaryl 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="chem0004" num="0004"><img file="EP2004755B1_D0004.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.

0036Particularly 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.

0037In particular, the dyes of formula (II) have a group Y which represents an alkali metal or a protective group such as:<ul id="ul0010" 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>➢ 5-6-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="chem0005" num="0005"><img file="EP2004755B1_D0005.tif" /></chemistry></li><li>➢ isothiouronium -C (NH₂) = N⁺H₂, Year^- ;</li><li>➢ isothiourea -C (NH₂) = NH;</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>

0038According to a particular embodiment of the invention, the fluorescent dyes of the invention are of formula (la) or (IIa), each having an ethylene group which connects the pyridinium part to the phenyl in the ortho or para position or in positions 4-4 ', 4-2' or 2-4 ':<chemistry id="chem0006" num="0006"><img file="EP2004755B1_D0006.tif" /></chemistry><chemistry id="chem0007" num="0007"><img file="EP2004755B1_D0007.tif" /></chemistry>formula (la) and (IIa) with R₁, R₂, R₃, R₄, R_at, R_b, R_i, R '_i, R_g, R '_g, R_h, R '_h, m, n, Y, R '₁, R '₂, R '₃, R '₄, R '_at, R '_b, R "_i, R "'_i, R "_g, R "'_g, R "_h, R "'_h, m 'and n' are as defined above.

0039Another particular embodiment of the invention relates to disulfide dyes of formula (I) or (la) symmetrical ie R_at, R_b, R_g, R '_g, R_h, R '_h, R_i, R '_i, R_i, R₂, R₃. R₄, T_at, m, n are identical to R '_at, R '_b, R "_g, R "'_g, R "_h, R '' '_h, R "_i, R "_i, R '₁, R '₂, R '₃, R '₄, T_b, m 'and n' respectively.

0040By way of example of thiol fluorescent dyes, mention may be made in particular of the following dyes:<tables id="tabl0001" num="0001"><table frame="all"><tgroup cols="2"><colspec colnum="1" colname="col1" colwidth="79mm" /><colspec colnum="2" colname="col2" colwidth="84mm" /><tbody><row><entry namest="col1" nameend="col2" align="center"><chemistry id="chem0008" num="0008"><img file="EP2004755B1_D0008.tif" /></chemistry></entry></row><row><entry namest="col1" nameend="col2" align="center"><b>1</b></entry></row><row><entry align="center"><chemistry id="chem0009" num="0009"><img file="EP2004755B1_D0009.tif" /></chemistry></entry><entry align="center"><chemistry id="chem0010" num="0010"><img file="EP2004755B1_D0010.tif" /></chemistry></entry></row><row><entry align="center"><b>2</b></entry><entry align="center"><b>3</b></entry></row><row><entry align="center"><chemistry id="chem0011" num="0011"><img file="EP2004755B1_D0011.tif" /></chemistry></entry><entry align="center"><chemistry id="chem0012" num="0012"><img file="EP2004755B1_D0012.tif" /></chemistry></entry></row><row><entry align="center"><b>3</b></entry><entry align="center"><b>4</b></entry></row><row><entry align="center"><chemistry id="chem0013" num="0013"><img file="EP2004755B1_D0013.tif" /></chemistry></entry><entry align="center"><chemistry id="chem0014" num="0014"><img file="EP2004755B1_D0014.tif" /></chemistry></entry></row><row><entry align="center"><b>5</b></entry><entry align="center"><b>6</b></entry></row><row><entry align="center"><chemistry id="chem0015" num="0015"><img file="EP2004755B1_D0015.tif" /></chemistry></entry><entry align="center"><chemistry id="chem0016" num="0016"><img file="EP2004755B1_D0016.tif" /></chemistry></entry></row><row><entry align="center"><b>7</b></entry><entry align="center"><b>8</b></entry></row><row><entry align="center"><chemistry id="chem0017" num="0017"><img file="EP2004755B1_D0017.tif" /></chemistry></entry><entry align="center"><chemistry id="chem0018" num="0018"><img file="EP2004755B1_D0018.tif" /></chemistry></entry></row><row><entry align="center"><b>9</b></entry><entry align="center"><b>10</b></entry></row><row><entry align="center"><chemistry id="chem0019" num="0019"><img file="EP2004755B1_D0019.tif" /></chemistry></entry><entry align="center"><chemistry id="chem0020" num="0020"><img file="EP2004755B1_D0020.tif" /></chemistry></entry></row><row><entry align="center"><b>11</b></entry><entry align="center"><b>12</b></entry></row><row><entry namest="col1" nameend="col2" align="center"><chemistry id="chem0021" num="0021"><img file="EP2004755B1_D0021.tif" /></chemistry></entry></row><row><entry namest="col1" nameend="col2" align="center"><b>13</b></entry></row><row><entry namest="col1" nameend="col2" align="center"><chemistry id="chem0022" num="0022"><img file="EP2004755B1_D0022.tif" /></chemistry></entry></row><row><entry namest="col1" nameend="col2" align="center"><b>14</b></entry></row><row><entry namest="col1" nameend="col2" align="center"><chemistry id="chem0023" num="0023"><img file="EP2004755B1_D0023.tif" /></chemistry></entry></row><row><entry namest="col1" nameend="col2" align="center"><b>15</b></entry></row><row><entry namest="col1" nameend="col2" align="center"><chemistry id="chem0024" num="0024"><img file="EP2004755B1_D0024.tif" /></chemistry></entry></row><row><entry namest="col1" nameend="col2" align="center"><b>16</b></entry></row><row><entry namest="col1" nameend="col2" align="center"><chemistry id="chem0025" num="0025"><img file="EP2004755B1_D0025.tif" /></chemistry></entry></row><row><entry namest="col1" nameend="col2" align="center"><b>17</b></entry></row><row><entry namest="col1" nameend="col2" align="center"><chemistry id="chem0026" num="0026"><img file="EP2004755B1_D0026.tif" /></chemistry></entry></row><row><entry namest="col1" nameend="col2" align="center"><b>18</b></entry></row><row><entry namest="col1" nameend="col2" align="center"><chemistry id="chem0027" num="0027"><img file="EP2004755B1_D0027.tif" /></chemistry></entry></row><row><entry namest="col1" nameend="col2" align="center"><b>19</b></entry></row><row><entry namest="col1" nameend="col2" align="center"><chemistry id="chem0028" num="0028"><img file="EP2004755B1_D0028.tif" /></chemistry></entry></row><row><entry namest="col1" nameend="col2" align="center"><b>20</b></entry></row><row><entry namest="col1" nameend="col2" align="center"><chemistry id="chem0029" num="0029"><img file="EP2004755B1_D0029.tif" /></chemistry></entry></row><row><entry namest="col1" nameend="col2" align="center"><b>21</b></entry></row><row><entry namest="col1" nameend="col2" align="center"><chemistry id="chem0030" num="0030"><img file="EP2004755B1_D0030.tif" /></chemistry></entry></row><row><entry namest="col1" nameend="col2" align="center"><b>22</b></entry></row><row><entry namest="col1" nameend="col2" align="center"><chemistry id="chem0031" num="0031"><img file="EP2004755B1_D0031.tif" /></chemistry></entry></row><row><entry namest="col1" nameend="col2" align="center"><b>23</b></entry></row><row><entry namest="col1" nameend="col2" align="center"><chemistry id="chem0032" num="0032"><img file="EP2004755B1_D0032.tif" /></chemistry></entry></row><row><entry namest="col1" nameend="col2" align="center"><b>24</b></entry></row><row><entry namest="col1" nameend="col2" align="center"><chemistry id="chem0033" num="0033"><img file="EP2004755B1_D0033.tif" /></chemistry></entry></row><row><entry namest="col1" nameend="col2" align="center"><b>25</b></entry></row><row><entry namest="col1" nameend="col2" align="center"><chemistry id="chem0034" num="0034"><img file="EP2004755B1_D0034.tif" /></chemistry></entry></row><row><entry namest="col1" nameend="col2" align="center"><b>26</b></entry></row><row><entry namest="col1" nameend="col2" align="center"><chemistry id="chem0035" num="0035"><img file="EP2004755B1_D0035.tif" /></chemistry></entry></row><row><entry namest="col1" nameend="col2" align="center"><b>27</b></entry></row><row><entry namest="col1" nameend="col2" align="center"><chemistry id="chem0036" num="0036"><img file="EP2004755B1_D0036.tif" /></chemistry></entry></row><row><entry namest="col1" nameend="col2" align="center"><b>28</b></entry></row></tbody></tgroup></table></tables>with M ', An^-, identical or different, representing an anionic counterion.

0041With M 'and An^-, identical or different, represent in particular a counterion such as halides, such as chloride, bromide; nitrates; sulfonates including C₁-VS₆ alkylsulfonates: Alk-S (O)₂O^- such as methylsulfonate or mesylate and ethylsulfonate; arylsulfonates: Ar-S (O)₂O^- such as benzenesulfonate and toluenesulfonate or tosylate; citrate; succinate; tartrate; lactate; alkyl sulfates: Alk-OS (O) O^- such as methyl sulfate and ethyl sulfate; arylsulfates: Ar-OS (O) O^- such as benzenesulfate and toluenesulfate; alkoxysulfates: Alk-OS (O)₂O^- such as methoxy sulfate and ethoxysulfate; aryloxysulfates: Ar-OS (O)₂O^-, phosphate; acetate; triflate; and borates such as tetrafluoroborate.

0042Protected thiol dyes of formula <b>(II)</b> can be synthesized in two stages. The first step consisting in preparing the unprotected thiol dye 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>.

0043We can illustrate this method by the method consisting in i) generating thiol fluorescent dyes by reduction of a fluorescent dye to two chromophores carrying a disulfide function -SS- such as <b>(I)</b> and ii) to protect by conventional methods said thiol function the compounds <b>(II ')</b> to access the protected thiol fluorescent dyes of formula <b>(II "):</b><chemistry id="chem0037" num="0037"><img file="EP2004755B1_D0037.tif" /></chemistry>with R_1' R₂, R₃, R₄, R_at, R_b, R_g, R '_g, R_h, R '_h, R_i, R '_i, T_at, m, n and M 'are as defined above and R represents a nucleofuge leaving group, such as for example mesylate, tosylate, triflate or halide, and Y' represents a group protecting the thiol function.

0044Alternatively, a protected thiol compound can be reacted <b><u>(b)</u></b> by a protective group Y 'as defined above prepared according to one of the procedures described in the works cited above, said protected thiol compound comprising at least one nucleophilic function with a sufficient quantity, preferably equimolar, of a "reactive fluorescent chromophore" or d 'a compound comprising such a "reactive fluorescent chromophore" <b><u>(at)</u>.</b> In other words <b><u>(at)</u></b> includes a nucleofuge function to form a covalent bond ∑ as can be schematized below:<chemistry id="chem0038" num="0038"><img file="EP2004755B1_D0038.tif" /></chemistry><chemistry id="chem0039" num="0039"><img file="EP2004755B1_D0039.tif" /></chemistry>with R₁, R₂, R₃, R₄, R_at, R_b, R_g, R '_g, R_h, R '_h, R_i, R '_i, Y ', m, n and M' are as defined above; Nu representing an amino, oxygenated nucleophilic group such as primary amine, hydroxy, thiol; E representing an electrophilic group comprising a carbonyl, a thiocarbonyl such as an acyl halide, acyl thiohalide, an ester, a thioester. It follows that ∑ represents a chain of radicals chosen from -SO₂-, -O-, -S-, -N (R) -, -CO-, with R, represents a hydrogen atom, a C 1 alkyl radical₁-VS₄, C-hydroxyalkyl₁-VS₄; or an aryl (C₁-VS₄) alkyl, in particular ∑ represents a group chosen from -C (O) -N (R) -, -C (O) -O-, -C (S) -O-, -C (O) -S-, - C (S) -S- or -C (S) -N (R) -.

0045It is also possible to use a thiol reagent Y-SH comprising a group Y of which the 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 <b>(II):</b><chemistry id="chem0040" num="0040"><img file="EP2004755B1_D0040.tif" /></chemistry>with R₁, R₂, R₃, R₄, R_at, R_b, R_g, R '_g, R_h, R '_h, R_i, R '_i, T_at, Y, m, n and M 'are as defined above, and Hal representing a nucleofuge halogen atom such as bromine, iodine or chlorine.

0046We can also use a thioacid <u><b>(</b>α<b>)</b></u> (for example thioacetic acid) which will act on the halide carried by the fluorescent chromophore <b>(<u>at'</u>)</b> : <chemistry id="chem0041" num="0041"><img file="EP2004755B1_D0041.tif" /></chemistry>with R₁, R₂, R₃, R₄, R_at, R_b, R_g, R '_g, R_h, R '_h, R_i, R '_i, m, n, T_at, M 'are as defined above and R' representing a group (C₁-VS₆) alkyl.

0047More particularly, it is possible to replace a leaving nucleofuge group with a thiourea group (S = C (NRR) NRR) to generate isothiouroniums. For example if the thiourea group is a thioimidazolinium (β), the reaction scheme is as follows:<chemistry id="chem0042" num="0042"><img file="EP2004755B1_D0042.tif" /></chemistry>with R₁, R₂, R₃, R₄, R_at, R_b, R '_vs, R '_d, R_g, R '_g, R_h, R '_h, R_i, R '_i, m, n, T_at, Year^- and M 'are as defined above.

0048A 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.

0049According to another variant, it is possible to generate an imidazoline intermediate from the halide comprising the fluorescent chromophore <b><u>(at')</u></b> and a thioimidazoline <b>(b ')</b> to conduct after alkylation with a reagent R-Gp with R representing an alkyl group and Gp a leaving group such as a halogen such as chlorine, bromine, iodine, or a mesylate or tosylate group, to yield the dye of formula <b>(II "").</b><chemistry id="chem0043" num="0043"><img file="EP2004755B1_D0043.tif" /></chemistry>

0050It is also possible to substitute a leaving nucleofuge group with the thiosulfate salts (for example sodium or potassium thiosulfate) to generate the Bunte salts (-SSO^-_s, N / A⁺ or K⁺) : <chemistry id="chem0044" num="0044"><img file="EP2004755B1_D0044.tif" /></chemistry>with R₁, R₂, R₃, R₄, R_at, R_b, R_g, R '_g, R_h, R '_h, R_i, R '_i, m, n, T_at, M 'are as defined above and M⁺ representing an alkali metal such as sodium or potassium.

0051In accordance with another possibility, certain protected thiol fluorescent dyes <b>(II ")</b> can be obtained by reacting a protected thiol compound with a compound carrying a nucleofuge or carbonyl function of the acyl halide type <b>(<u>d</u>)</b> reacted with a fluorescent chromophore carrying a nucleophilic function <b>(<u>vs</u>)</b>. primary or secondary amine type:<chemistry id="chem0045" num="0045"><img file="EP2004755B1_D0045.tif" /></chemistry>with R₁, R₂, R₃, R₄, R_at, R_b, R_g, R '_g, R_h, R '_h, R_i, R '_i, T_at, Y, m, n, M ', <img file="EP2004755B1_D0046.tif" /> and <b>(II ")</b> as defined above and <img file="EP2004755B1_D0047.tif" /> representing an electrophilic group comprising a carbonyl, a thiocarbonyl such as an acyl halide, acyl thiohalide, an ester, a thioester. It follows that Σ represents a chain of radicals chosen from -SO₂-, -O-, -S-, -N (R) -, -CO-, with R, represents a hydrogen atom, a C 1 alkyl radical₁-VS₄, C-hydroxyalkyl₁-VS₄; or an aryl (C₁-VS₄) alkyl, in particular Σ represents a group chosen from -N (R) -C (O) -, -OC (O) -, -OC (S) -, -SC (O) -, SC (S) - or - N (R) -C (S) -.

0052A variant is to use a thiolactone capable of undergoing the nucleophilic attack of an amino group carried by the chromophore styrylpyridinium (c ') to lead to the fluorescent dye thiol <b>(II '_at)</b> which can either be protected or be metallized to give the dyes respectively <b>(II ''_at)</b> and <b>(II ''_atputs)</b> as the following diagram illustrates:<chemistry id="chem0046" num="0046"><img file="EP2004755B1_D0048.tif" /></chemistry>According to another possibility, the protected thiol fluorescent dyes of formula <b>(II)</b> can be obtained by reaction of a compound comprising a thiol group protected by a group Y, and a hydroxy group activated beforehand in a leaving group nucleofuge <b>(<u>of</u>),</b> for example mesylate, tosylate, triflate or halide with a fluorescent chromophore <b>(<u>vs'</u>)</b> carrying a primary amine nucleophilic function when R_b represents a hydrogen atom, or secondary amine.<chemistry id="chem0047" num="0047"><img file="EP2004755B1_D0049.tif" /></chemistry>

0053With R₁, R₂, R₃, R₄, R_at, R_b, R_g, R '_g, R_h, R '_h, R_i, R '_i, T_at, Y, m, n, and M 'are as defined above and <img file="EP2004755B1_D0047.tif" /> represents a nucleofuge group such as for example mesylate, tosylate, triflate or halide.

0054According to another possibility, the thiol fluorescent dyes of formula <b>(II)</b> according to the invention can be obtained by reaction of a compound comprising a protected thiol group and an electrophilic group <b><u>(f)</u></b> with a compound comprising a nucleophilic group. For example, we can condense an aldehyde or ketone when G represents an oxygen atom 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 for example mentioned in the patent<patcit id="pcit0007" dnum="DE19951134"><text>DE19951134</text></patcit> there may be mentioned in particular 1,2-dialkylpyridinium and in particular 1,2-dimethylpyridinium:<chemistry id="chem0048" num="0048"><img file="EP2004755B1_D0050.tif" /></chemistry>with R₁, R₂, R₃, R₄, R_at, R_b, R_g, R '_g, R_i, R '_h, R '_i, T_at, Y, m, n, M 'as defined above and G representing an oxygen or sulfur atom or an NR "group with R" representing a hydrogen atom or an alkyl group.

0055Another variant of this reaction scheme is to carry out the “Knoevenagel” coupling reaction later on, ie from the intermediate <b><u>(f ')</u>,</b> the amino group R'NH can react with an equivalent of reagent <img file="EP2004755B1_D0047.tif" /> - (CR₃R₄)-<img file="EP2004755B1_D0047.tif" /> to lead to <b><u>(i ')</u></b> which itself can react with a protected thiol derivative Y'SH to give the aldehyde intermediate <b><u>(i ')</u>.</b> This intermediate can undergo the condensation reaction of "Knoevenagel" with alkylpyridinium <b><u>(e)</u></b> to lead to the protected thiol fluorescent dye <b>(II '').</b><chemistry id="chem0049" num="0049"><img file="EP2004755B1_D0051.tif" /></chemistry>with R ', R₁, R₂, R₃, R₄, R_at, R_b, R_g, R '_g, R_i, R '_h, R_i, R '_i, <img file="EP2004755B1_D0047.tif" />, m, n, Y ', and M' as defined, and Σ notably represents an N (R) -C (O) -, or -N (R) -C (S) -.

0056We 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.

0057The thiol fluorescent dyes formed can be transformed into thiol protected fluorescent dyes -SY 'by the protection of thiol -SH using the conventional protective groups. The thiol fluorescent dyes can also be metallized 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>.

0058The 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>.

0059The starting reagents are commercial or accessible by conventional routes known to those skilled in the art. By way of example, in order to synthesize the fluorescent dye with two chromophores carrying a disulfide function -SS- (I '), it is possible to start from a difunctionalized reagent<b><u>(k)</u>,</b> comprising at position 1 a nucleofuge group GR with R representing a group (C₁-VS₄) alkyl, mesylate, tosylate, or triflate and G representing an oxygen or sulfur atom or a halogen such as fluorine, chlorine, iodine, and comprising in position 2 or 4 an electrophilic aldehyde or thioaldehyde group. Two equivalents of this reagent can react with diamine-dialkyl-disulfide<b>(<u>I</u>)</b> to conduct after condensation with diketone / thioalketone disulfide <b><u>(m)</u></b> can condense with two alkylpyridinium equivalents <b><u>(e)</u></b> to form the compound <b>(<u>I '</u>).</b><chemistry id="chem0050" num="0050"><img file="EP2004755B1_D0052.tif" /></chemistry>

0060We can refer to the book <nplcit id="ncit0014" npl-type="b"><text>Advanced Organic Chemistry, 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.

0061The disymmetric disulfide dyes of formula <b>(I)</b> can be synthesized in one step by reacting an unprotected thiol fluorescent dye with a protected thiol fluorescent dye to form the disulfide dye of formula <b>(I).</b><chemistry id="chem0051" num="0051"><img file="EP2004755B1_D0053.tif" /></chemistry>with R_at, R '_at, R_b, R '_b, R_g, R '_g, R ''_g, R ''_g, R_h, R '_h, R ''_h, R '' '_h, R_i, R '_i, R ''_i, R '' '_i, R '₁, R₂, R '₂, R₃, R '₃, R₄, R '₄, m, m ', n, n', T_at, T_b and M 'are as defined above; Y 'represents a protective group of thiol function.

0062The composition of the invention contains at least one fluorescent dye of formula (I) or (II). In addition to the presence of at least one thiol fluorescent dye of formula (I), the composition of the invention may also contain a reducing agent. This 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, trimethoxy-borohydride: sodium salts, lithium, potassium, calcium, quaternary ammoniums (tetramethylammonium, tetraethylammonium, tetra n-butylammonium, benzyltriethyl-ammonium); catecholborane.

0063The dye composition useful in the invention generally contains an amount of fluorescent dyes 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.

0064The 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, acidic or cationic azo 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.

0065Among the natural direct dyes, mention may be made of lawsone, juglone, alizarin, purpurin, carminic acid, kermesic acid, purpurogallin, protocatechaldehyde, indigo, isatin, curcumin, spinulosin, apigenidine. One can also use extracts or decoctions containing these natural dyes and in particular poultices or extracts based on henna.

0066The dye composition may contain one or more oxidation bases and / or one or more couplers conventionally used for dyeing keratin fibers.

0067Among the oxidation bases, mention may be made of para-phenylenediamines, bisphenylalkylenediamines, para-aminophenols, bis-para-aminophenols, ortho-aminophenols, heterocyclic bases and their addition salts

0068Among these couplers, mention may in particular be made of meta-phenylenediamines, meta-aminophenols, meta-diphenols, naphthalene couplers, heterocyclic couplers and their addition salts.

0069The 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%.

0070The 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.

0071In 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.

0072The 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.

0073The 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.

0074The dye composition may also contain various adjuvants conventionally used in compositions for dyeing 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 not, such as silicones amines, film-forming agents, ceramides, preserving agents, opacifying agents, conductive polymers.

0075The 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.

0076Of 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.

0077The 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.

0078Among 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.

0079Among 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="chem0052" num="0052"><img file="EP2004755B1_D0054.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.

0080The 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.

0081The dyeing process of the invention consists in applying the composition of the invention to keratin materials, in particular keratin fibers, in particular human fibers such as the hair, more particularly dark hair, the dye composition of the invention comprising at least minus a fluorescent dye of formula (I) or (II).

0082According 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 (I) or (II).

0083This 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.

0084This 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.

0085According to another method, the composition comprising at least one fluorescent dye of formula (I) or (II) also contains at least one reducing agent as defined above. This composition is then applied to the hair.

0086When the fluorescent dye (I) or (II) comprises a group Y which protects 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.

0087For example, it is possible to deprotect 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 valign="top">protection</entry></row></thead><tbody><row><entry /><entry /></row><row><entry>alkylcarbonyl,</entry><entry>pH> 9</entry></row><row><entry>arylcarbonyl,</entry><entry>pH> 9</entry></row><row><entry>alkoxycarbonyl,</entry><entry>pH> 9</entry></row><row><entry>aryloxycarbonyl,</entry><entry>pH> 9</entry></row><row><entry>arylalkoxycarbonyl</entry><entry>pH> 9</entry></row><row><entry>(di) (alkyl) aminocarbonyl,</entry><entry>pH> 9</entry></row><row><entry>(alkyl) arylaminocarbonyl</entry><entry>pH> 9</entry></row><row><entry>optionally substituted aryl such as phenyl,</entry><entry>pH> 9</entry></row><row><entry>5-, 6- or 7-membered monocyclic heteroaryl such as oxazolium;</entry><entry>pH> 9</entry></row><row><entry>8 to 11 membered bicyclic heteroaryl such as benzoimidazolium, or benzoxazolium</entry><entry>pH> 9</entry></row></tbody></tgroup></table></tables>

0088The deprotection step can also be carried out during a hair pretreatment step such as, for example, the reducing hair pretreatment.

0089According to another coloring process, the composition comprising at least one fluorescent dye of formula (I) or (II) also contains at least one reducing agent as defined above. This composition is then applied to the hair.

0090Alternatively, the reducing agent is added to the dye composition containing at least one fluorescent dye (I) or (II) at the time of use.

0091According to another variant, the reducing agent is applied in post-treatment, after the application of the composition containing at least one fluorescent dye (I) or (II). 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.

0092A particular embodiment of the invention relates to a process in which the fluorescent dye of formula (I) or (II) can be applied directly to the hair without reducing agents, free from reducing pre or post-treatment.

0093A treatment with an oxidizing agent may possibly be combined. Any type of conventional oxidizing agent can be used in the field. 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.

0094This oxidizing agent can be applied to the fibers before or after the application of the composition containing at least one fluorescent dye of formula (I) or (II).

0095The 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.

0096The 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 (I) or (II) and a second compartment contains a reducing agent. capable of reducing the disulfide functions of keratin materials.

0097One of these compartments may also contain one or more other dyes of the direct dye or oxidation dye type.

0098It 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 (I) or (II); a second compartment contains a reducing agent capable of reducing the disulfide bond of keratin materials; a third compartment contains an oxidizing agent.

0099Another variant relates to a device with several compartments or "kit" for dyeing comprising a first compartment which contains a composition with at least one protected fluorescent dye of formula (II) and a second compartment comprising a composition containing a deprotective agent such as a base.

0100Each 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="pcit0008" dnum="FR2586913"><text>FR2 586 913</text></patcit>.

0101The examples which follow serve to illustrate the invention without, however, being limiting in nature. The 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 the salt of 4 - ((E) -2- {4 - [(4,13-dimethyl-17- {4 - [(E) -2- (1-methylpyridinium-4-yl) vinyl] phenyl} - 5,12-dioxo-8,9-dithia-4,13,17-triazaoctadéc-1-yl) (methyl) amino] phenyl} vinyl) -1-methylpyridinium [1]

0102<chemistry id="chem0053" num="0053"><img file="EP2004755B1_D0055.tif" /></chemistry><chemistry id="chem0054" num="0054"><img file="EP2004755B1_D0056.tif" /></chemistry>

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

8.64 mL of 4-fluorobenzaldehyde, 13.36 g of potassium carbonate and 30 mL of N-methylpyrrolidinone (NMP) are mixed with stirring and heating to 110 ° C. 11.9 mL of 1,3-bis (methylamino) propane are added dropwise to the reaction medium maintained under stirring and heating at 110 ° C for 3 days. The reaction mixture is concentrated and 54 g of oil collected.

Step 2: Synthesis of 1-methyl-4 - [(E) -2- (4- {methyl [3- (methylamino) -propyl] amino} phenyl) vinyl] pyridinium acetate

010325 g of 4- {methyl [3- (methylamino) propyl] amino} benzaldehyde in solution in 30 ml of isopropanol and 10.9 ml of pyrrolidine are stirred at room temperature for 10 min. 7.6 ml of acetic acid are added to the reaction medium maintained under stirring at 20 ° C for 20 min. 26.55 g of 1,4-dimethylpyridinium methyl sulfate diluted in 20 mL of isopropanol are added. The reaction medium is kept stirring at room temperature for 5 days. The mixture obtained is extracted 3 times with dichloromethane (DCM), concentrated and purified by liquid water / butanol chromatography. After vacuum concentration of the pure fractions, 3.4 g of red powder are collected.

Step 3: Synthesis of the salt of 4 - ((E) -2- {4 - [(4,13-dimethyl-17- {4 - [(E) -2- (1-methylpyridinium-4-yl) vinyl] phenyl} -5,12-dioxo-8,9-dithia-4,13,17-triazaoctadec-1-yl) (methyl) amino] phenyl} vinyl) -1-methylpyridinium

01041.63 g of 1-methyl-4 acetate - [(E) -2- (4- {methyl [3- (methylamino) propyl] amino} phenyl) -vinyl] pyridinium are dissolved in 5 ml of acetonitrile (ACN). 600 µL of diisopropylethylamine (DIPEA), 420 mg of 3,3'-dithiopropanoic acid then 1.09 g of (1H-1,2,3-benzotriazol-1-yloxy) hexafluorophosphate (tripyrrolidin-1-yl) -phosphonium are added to the mixture. After 24 h of stirring at room temperature, the mixture is concentrated and purified by chromatography on silica gel (reverse phase grafted C₁₈ ; elution water / ACN / trifluoroacetic acid 0.1%). The pure fractions are combined and neutralized by adding sodium hydrogencarbonate, concentrated in vacuo and the solid obtained is taken up in an acetone / ACN mixture. After filtration, the evaporation of the solvents leads to a red solid of mass 1.77 g. Analyzes indicate that the product obtained conforms to the expected structure. The counter ions An- consist of a mixture of trifluoroacetate and hydrogen carbonate. LCMS: positive ions m / z = 383, 256 and 192 corresponding respectively to [M / 2]²⁺, [M + H]³⁺ and [M + 2H]⁴⁺. λ_max 468 nm.

<u>Exempt 2:</u> Synthesis of the salt of 1-methyl-4 - {(E) -2- [4- (methyl {3- [methyl (3-sulfanylpropanoyl) -amino] propyl} amino) phenyl] vinyl} pyridinium [2]

0105<chemistry id="chem0055" num="0055"><img file="EP2004755B1_D0057.tif" /></chemistry><chemistry id="chem0056" num="0056"><img file="EP2004755B1_D0058.tif" /></chemistry>

Step 1: Synthesis of the salt of 1-methyl-4 - {(E) -2- [4- (methyl) {3- [methyl (3-sulfanyl-propanoyl) amino] propyl} amino) phenyl] vinyl} pyridinium [ 2]

010660 mg of the salt of 1-methyl-4 - {(E) -2- [4- (methyl {3- [methyl (3-sulfanylpropanoyl) -amino] propyl} amino) phenyl] vinyl} pyridinium are dissolved in 10 ml of water / ethanol mixture 1: 1; 2 eq. 3- [bis (2-carboxy-ethyl) phosphino] propanoic acid hydrochloride hydrate dissolved in 1 ml of water and 4 eq of sodium bicarbonate dissolved 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 very largely contains the expected product <b>[2].</b><ul id="ul0011" 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 + 0.1% formic acid / B: ACN</li><li>Linear gradient: T (min) A% / B%: 0 min 95/5; 8 min 0/100</li><li>Flow rate: 1mL / min.</li><li>Detection: UV Diode array λ = 400-700nm</li><li>MS (ESI +): corresponds to the mass peak of the monocation of the expected product [2]</li></ul>

COLORING EXAMPLES

<u>Example 1</u> : Coloring process - compound [1]

Preparation of composition A

0107<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 [1]</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

0108<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">1M</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>

0109At 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).

0110After 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.

<u>Example 2</u> : dyeing process with the compound [2]

011110 mL of fresh solution of the compound <b>[2]</b> of the synthetic example are applied to a lock of 1g of hair, tone height 4, placed at the bottom of a bowl for 30 minutes at room temperature (the locks are turned over and re-impregnated after 15 minutes).

0112The locks are then rinsed with running water and dried.

0113After coloring, the pitch of tone 4 became visually clearer than untreated control strands.

Remanence towards successive shampoos:

0114The 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

0115During shampooing, there is no visible bleeding, the foam of the shampoos and the rinsing waters are not colored

0116The observed color is preserved and the lightening effect remains visible on the hair of tone 4 height thus treated.

Results in the L * a * b * system:

0117The 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).

0118In this system L * a * b *, L * represents the brightness, a * indicates the green / red color axis and b * the blue / yellow color axis. 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.

0119The 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>-</mo><msub><mi mathvariant="normal">L</mi><mi mathvariant="normal">o</mi></msub><mo mathvariant="normal">*</mo></mfenced><mn mathvariant="normal">2</mn></msup><mo mathvariant="normal">+</mo><msup><mfenced><mi mathvariant="normal">at</mi><mo mathvariant="normal">*</mo><mo>-</mo><msub><mi mathvariant="normal">at</mi><mi mathvariant="normal">o</mi></msub><mo mathvariant="normal">*</mo></mfenced><mn mathvariant="normal">2</mn></msup><mo mathvariant="normal">+</mo><msup><mfenced><mi mathvariant="normal">b</mi><mo mathvariant="normal">*</mo><mo>-</mo><msub><mi mathvariant="normal">b</mi><mi mathvariant="normal">o</mi></msub><mo mathvariant="normal">*</mo></mfenced><mn mathvariant="normal">2</mn></msup></msqrt></math><img file="EP2004755B1_D0059.tif" /></maths>

0120In 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).

0121The 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="5"><colspec colnum="1" colname="col1" colwidth="44mm" /><colspec colnum="2" colname="col2" colwidth="13mm" /><colspec colnum="3" colname="col3" colwidth="12mm" /><colspec colnum="4" colname="col4" colwidth="12mm" /><colspec colnum="5" colname="col5" colwidth="12mm" /><thead><row><entry align="center" valign="top"><b>Compound</b></entry><entry align="center" valign="top"><b>L *</b></entry><entry align="center" valign="top"><b>at*</b></entry><entry align="center" valign="top"><b>b *</b></entry><entry align="center" valign="top">Δ <b>E</b></entry></row></thead><tbody><row><entry align="center">HT4 wick reference</entry><entry align="center">17,27</entry><entry align="center">2,78</entry><entry align="center">3,19</entry><entry align="center" /></row><row><entry align="center">Compound 1</entry><entry align="center">19,36</entry><entry align="center">8,32</entry><entry align="center">9,20</entry><entry align="center">8,45</entry></row><row><entry align="center">Compound 1 - 5 shampoos</entry><entry align="center">19,58</entry><entry align="center">8,37</entry><entry align="center">9,09</entry><entry align="center">8,45</entry></row></tbody></tgroup></table></tables>

0122The 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:

0123The 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.

0124The 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, (see <figref idref="f0001">figure 1</figref>).

0125It 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.

0126In addition, the results show that the reflectance of the locks of hair having a tone height 4 treated with the composition 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.