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

Translation of description of equivalent WO 2007110533 A2

p0001DYE COMPOSITION CONTAINING A FLUORESCENT DYE THIOL / DISULPHIDE, EXTERNAL CATIONIC CHARGE AND CHAIN ​​ALKYLENE MISSED METHOD OF LIGHTENING

KERATIN MATERIALS USING THIS DYE

p0003The invention relates to the dyeing of keratin fibers using fluorescent dyes thiols / disulfides pyridinium cationic charge and external alkylene chain interrupted.

p0004It is known to dye keratin fibers, particularly human, by direct dyeing. The process conventionally used in direct dyeing comprises applying to the keratin fibers direct dyes, which are colored and coloring molecules that have affinity for the fibers, allowing them to diffuse and then rinsing the fibers.

p0005The direct dyes which are conventionally used are for example dyes of the nitrobenzene type, anthraquinone dyes, nitropyridine dyes of the azo, xanthene, acridine, azine or triarylmethane.

p0006The colorations resulting from the use of direct dyes are temporary or semi-permanent colorings since the nature of the interactions that bind the direct dyes to the keratin fiber, and their desorption from the surface and / or the heart of the fiber are responsible their low dyeing power and their poor resistance to washing or perspiration.

p0007Furthermore, the dyeing of keratinous fibers from conventional direct dyes does not allow to significantly lighten keratin fibers. The lightening of the color of keratin fibers, especially dark to lighter shades, by optionally modifying the shade thereof, constitutes an important demand.

p0008Conventionally, to obtain a lighter coloring implements a chemical bleaching process. This method comprises treating keratin materials such as keratin fibers, in particular hair, with a strong oxidizing system, generally consisting of hydrogen peroxide associated or not with persalts, usually under alkaline conditions.

p0009This bleaching system has the disadvantage of degrading keratin materials, especially keratin fibers, especially human such as hair and impairing their cosmetic properties. The fibers have a tendency to become rough, more difficult to disentangle and more brittle. Finally, the lightening or bleaching of keratin fibers with oxidizing agents is incompatible with the treatments for modifying the shape of said fibers, particularly in hair straightening treatments.

p0010Another lightening technique comprises applying dark hair fluorescent direct dyes. This technique, described in particular in documents FR 2830189 and WO 2004/091473 allows to respect the quality of the keratin fiber during the treatment, but the fluorescent dyes employed do not exhibit satisfactory resistance to shampoos.

p0011To increase the toughness of direct dyeing, it is known to fix direct dyes by covalent bonding to the hair. For example, it is known to react with reactive groups in dyes residues cystine or cysteine ​​in many keratin fibers see for example the Journal of the Society of Dyers and Colourists, Guise and Stapleton, 9_1, 259-264 ( 1975); Journal of Cosmetic Chemistry, 42, 1-17 (1991); CA 2024509;

p0012Furthermore it is known to protect or thiol functions in one molecule to be grafted to the hair before applying said hair WO 99/51 194. However, this application does not mention the use of fluorescent dyes for coloring or lighten hair.

p0013Other disulphide dyes known for coloring keratin fibers are disulphide derivatives of aminothiophenol derivatives. Such dyes are described for example in FR 1 156407. These dyes may be used under relatively mild conditions in the presence of a slightly reducing medium or after a reducing pre-treatment of the hair. However, these dyes can cause colourshifts when applying.

p0014Finally, WO 2005/097051 describes the document disulfide dyes aza imidazoliums for the direct dyeing of keratin fibers.

p0015The object of the present invention is to provide new dyeing keratin materials systems in particular human keratin fibers, in particular hair, which do not present the drawbacks of the existing bleaching processes. In particular, an object of the present invention is to provide direct dyeing systems for obtaining lightening effects including keratin fibers naturally or artificially dark, which are resistant to successive shampooing, which do not degrade the keratin fibers and which do not alter their cosmetic properties.

p0016This object is achieved with the present invention which relates to a keratinous material dyeing process, in particular keratin fibers, especially human such as the hair, especially dark hair, consisting in applying to keratin materials, a dye composition comprising, in a suitable cosmetic medium, at least one thiol fluorescent dye pyridinium external cationic charge selected from the dyes of formula (I) or (II):

p0017<img id="imgf000004_0001" he="44" wi="143" file="imgf000004_0001.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="no" /> the organic or mineral acid salts, optical isomers, geometrical isomers, and solvates such as hydrates; formula (I) wherein:

p0018> R₃ and R '_at, Identical or different, represent an aryl (Cr C₄) Alkyl or a (d-Cβ) alkyl optionally substituted by hydroxyl or amino, -C₄ alkylamino, (Ci-C₄) Dialkylamino, said alkyl radicals possibly forming with the nitrogen atom carrying them, a heterocycle comprising from 5 to 7 members, optionally comprising another heteroatom identical to or different from nitrogen; preferably R₃ and R '_at represent a group (-C₃) Alkyl optionally substituted by hydroxy, or a benzyl group;

p0019> R_b and R'b, identical or different, represent a hydrogen atom, an aryl (Ci-C₄) Alkyl or a (C-rCβ) alkyl optionally substituted; including R_b and R '_b represent a hydrogen atom or a (C₁-C3) Alkyl or benzyl; > R₉, R '_g, R "_g and R " '_g, Identical or different, represent a hydrogen atom, an amino group, (CrC₄) Alkylamino, (-C₄) Dialkylamino, trifluoromethyl, acylamino, (-C₄) Alkoxy (-C₄) Alkylcarbonyloxy, (Cr C₄) Alkoxycarbonyl, (-C₄) Alkylcarbonylamino, (-C₄) Alkylsulfonylamino, radical (dC₃) Alkyl;

p0020> R_h, R'H, R "h and R" '_h, Identical or different, represent a hydrogen atom, a halogen atom, a dialkylamino group (C₁-C₄) (C Cr₄) Alkylcarbonylamino, acylamino, (Ci-C₄) Alkylsulfonylamino, or a (C₁-C₄) Alkyl; particularly R_h, R '_h, R "_h and R " '_h, Represent a hydrogen atom, or a (CrC₃) Alkyl;

p0021> Or else two groups R₉ 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, heterocycloalkyl fused or fused heteroaryl; the benzo, indeno, heterocycloalkyl or heteroaryl being optionally substituted by a halogen atom, an amino group, (C-rC₄) Alkylamino, (C₁- C₄) Dialkylamino, cyano, carboxy, hydroxy, trifluoromethyl, acylamino, alkoxy, -C₄(Poly) hydroxyalkoxy, C₂-C₄(-C₄) Alkylcarbonyloxy (C₁- C₄) Alkoxycarbonyl, (Ci-C₄) Alkylcarbonylamino, acylamino, carbamoyl, (Ci-C₄) Alkylsulfonyl-amino, aminosulfonyl, or a (Ci-Ci₆) Alkyl optionally substituted by a group selected from (Ci-Ci₂) Alkoxy, hydroxy, cyano, carboxy, amino, (Ci-C₄) Alkylamino and (Ci-C₄) Dialkylamino, or else the two alkyl radicals borne by the amino group nitrogen atom form a heterocycle comprising from 5 to 7 members and optionally comprising another heteroatom identical to or different than the nitrogen atom; particularly R₉ and R '_g ; R "_g and R " '_g together form a benzo group;

p0022> R, R ', R ", and R"' ι, identical or different, represent a hydrogen atom, or a (CrC₄) Alkyl; especially a hydrogen atom; > R₁, R₂R 3, R₄, R'-i, R '₂, R'3 and R ₄, Identical or different, represent a hydrogen atom or a (C₁-C₄) Alkyl, (C- | -C₁₂) Alkoxy, hydroxy, cyano, carboxyl, (di) (C₁-C₄) (Alkyl) amino, said alkyl radicals possibly forming with the nitrogen atom carrying them, a heterocycle comprising from 5 to 7 members, optionally comprising another heteroatom identical to or different from nitrogen; including R₁, R₂R 3 and R₄ are hydrogen atoms or a group

p0023(Di) (C "iC₄) (Alkyl) amino, preferably R₁, R₂, R'-i and R₂ represent a hydrogen atom and R₃, R₄, R '₃ or R '₄ represent a hydrogen atom or a (di) (CrC₄) (Alkyl) amino; the group (di) (-C₄) (Alkyl) amino is especially located in α binding T₃ 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 one of R₃, R₄ and / or one of the groups R '₃ and R '₄ may represent an amino group, said amino group is preferably located in α binding T_at and / or T_b when n or n 'is greater than 1; more preferably R₁, R₂, R₃, R₄, R ', R'₂, R '₃ and R '₄, Represent a hydrogen atom;

p0024> T_at and T_b, Identical or different, represent the combinations of the radicals selected from -SO₂-, -O-, -S-, -N (R) -, -CO-, where R, represents a hydrogen atom, an alkyl radical -C₄Hydroxyalkyl, -C₄; or an aryl (C Cr₄) Alkyl, particularly represent a group selected from -C (O) -N (R) -,

-N (R) -C (O) -;

p0026> M, m ', n and n', identical or different, represent an integer ranging from O to 6 with m + n and m '+ n', identical or different, represent an integer ranging between 1 and 10; particularly the sum m + n = m '+ n' is an integer ranging between 4 and 6;

p0027> M 'is an anionic ion-against; and

p0028> Y is i) a hydrogen atom; ii) an alkali metal; iii) an alkaline earth metal; iv) an ammonium group: N⁺R^αR ^ R^γR or 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 (dC₄) Alkyl; or v) a protective group of thiol; provided that when the compound of formula (I) or (II) contains other cationic parts, it is associated with one or more anionic against ions to achieve electroneutrality of the formula (I) or (II ). Another object of the invention is a dye composition comprising, in a suitable cosmetic medium, at least one fluorescent dye selected from the dyes of formula (I) or (II) as defined above, and optionally a reducing agent.

p0029The invention also relates to novel fluorescent dyes of formula (I) or (II) as defined above.

p0030The dyeing process according to the invention allows to visibly color dark keratin materials, in particular dark human keratin fibers, especially dark hair. Furthermore, the process of the invention allows to obtain a dyeing of keratin materials, in particular human keratinous fibers, especially hair, without damaging said material, volatile vis-a-vis of shampoos, common attacks (sun, perspiration ), and other hair treatments. The method of the invention also provides a lightening of keratin materials such as keratin fibers, particularly dark keratin fibers and more particularly dark hair.

p0031Within the meaning of the invention, the term dark keratin material which exhibits a lightness L^* in the CIEL system^*at^*b^*Less than or equal to 45 and preferably less than or equal to 40, given also that L^*= 0 is equivalent to black and L^*100 = white.

p0032Within the meaning of the invention, the term hair naturally or artificially dark hair whose tone height is less than or equal to 6 (dark blond) and preferably less than or equal to 4 (chestnut). The lightening of the hair is evaluated by the variation in "tone height" before and after application of the compound of formula (I) or (II).

p0033The notion of "tone" is based on the classification of natural shades, one tone separating each shade from the following or preceding immediately. This definition and classification of the natural shades are well known to hairstyling professionals and are published in the book "Science of hair treatment" of

p0034Charles Zviak 1988 Ed. Masson, p. 215 and 278.

p0035The tone heights range from 1 (black) to 10 (very light blond), one unit corresponding to one tone; the higher the number, the higher the grade is clear.

p0036An artificially colored hair is a hair whose color has been modified by for example a dyeing treatment, a dyeing with direct dyes or oxidation dyes.

p0037Preferably, the composition should, after application to the hair, for example chestnut, bring the results below.

p0038- We are interested in hair reflectance performance when irradiated with visible light in the wavelength range from 400 to 700 nanometers.

p0039- It then compares the reflectance curves as a function of wavelength, of hair treated with the composition of the invention and the untreated hair. - The curve corresponding to the treated hair should show a reflectance in the range of wavelengths from 500 to 700 nanometers higher than the curve corresponding to the untreated hair.

p0040- This means that, in the wavelength range from 540 to 700 nanometers, there is at least a range where the reflectance curve corresponding to the treated hair is higher than the reflectance curve corresponding to the untreated hair. The term "higher" is a difference of at least 0.05% reflectance and preferably at least 0.1%. This does not exclude that there may be in the wavelength range from 540 to 700 nanometers, at least a range where the reflectance curve corresponding to the treated hair is superimposable or lower than the reflectance curve corresponding to untreated hair.

p0041Preferably, the wavelength at which the difference is between the maximum reflectance curve of the treated hair and of the untreated hair is in the wavelength range from 500 to 650 nanometers, and preferably in the wavelength range of 550-620 nanometers.

p0042Within the meaning of the present invention, and unless a different indication is given: the radicals "aryl" or "heteroaryl" may be substituted by at least one substituent on a carbon atom selected from:. alkyl CRCI₆, Preferably -C₆ ;

p0043• a halogen atom such as chlorine, fluorine or bromine; . a hydroxyl group;

p0044• an alkoxy radical C₁-C₂ ; • a radical alkylthio, C₁-C₂ ;

p0045• a radical (poly) hydroxyalkoxy C₂-C₄ ; . an amino radical;

p0046• an amino radical substituted by one or two alkyl radicals, identical or different C₁-C₆ optionally bearing at least: i) hydroxy, ii) an amino group

p0047. acylamino (-NR-COR ') wherein the radical R is a hydrogen atom, an alkyl radical C₁-C₄ optionally bearing at least one hydroxyl group and the radical R 'is alkyl C₁-C₂ ; • a carbamoyl radical ((R)₂N-CO-) in which the radicals R, identical or different, represent a hydrogen atom, an alkyl radical dC₄ optionally bearing at least one hydroxyl group;

p0048. an alkylsulfonylamino radical (R¹SO₂-NR-) In which the radical R represents a hydrogen atom, an alkyl radical -C₄ optionally bearing at least one hydroxyl group and the radical R 'represents an alkyl radical dC₄ ;

p0049• an aminosulfonyl radical ((R)₂N-SO₂-) Wherein the radicals R, identical or different, represent a hydrogen atom, an alkyl radical C₁-C₄ optionally bearing at least one hydroxyl group, • a carboxyl group in acid or salified form (preferably with an alkali metal or an ammonium, substituted or unsubstituted);

p0050• a cyano group;

p0051. a polyhaloalkyl group having 1 to 6 carbon atoms and 1 to 6 halogen atoms, identical or different, the polyhaloalkyl group is for example trifluoromethyl; the cyclic or heterocyclic part of a non aromatic radical may be substituted by at least one substituent on a carbon atom selected from the groups: hydroxy,. C_rC₄Alkoxy dC₄(Poly) hydroxyalkoxy, C₂-C₄, An alkylthio radical -C₂ ,

p0052• RCO-NR'- wherein the radical R 'is a hydrogen atom or an alkyl radical C₁-C₄ and the radical R is a hydrogen atom, an alkyl radical C₁-C₂Or amino substituted with two alkyl groups are identical or different C₁-C₄ said alkyl radicals possibly forming with the nitrogen atom to which they are attached, a heterocycle comprising from 5 to 7 members, saturated or unsaturated, optionally substituted and optionally comprises at least one other heteroatom or may not be nitrogen;

p0053• RCO-O- wherein the radical R is an alkyl radical C₁-C₄And amino substituted with two alkyl groups are identical or different C₁-C₄, Said alkyl radicals possibly forming with the nitrogen atom to which they are attached, a heterocycle comprising from 5 to 7-membered saturated or unsaturated optionally substituted optionally comprising at least one other heteroatom or may not be nitrogen;

p0054• RO-CO- group wherein R is an alkyl radical C₁-C₄And amino substituted with two alkyl groups are identical or different dC₄ said alkyl radicals possibly forming with the nitrogen atom to which they are attached, a heterocycle comprising from 5 to 7 members, saturated or unsaturated, optionally substituted and optionally comprises at least one other heteroatom or may not be nitrogen;

p0055- An "aryl" radical represents a monocyclic or polycyclic group, condensed or not, comprising from 6 to 22 carbon atoms, and at least one ring is aromatic; preferably the aryl is phenyl, biphenyl, naphthyl, indenyl, anthracenyl or tetrahydronaphthyl;

p0056- A "diarylalkyl" radical represents a group having the same carbon atom of an alkyl group, two aryl groups, which are identical or different, such as diphenylmethyl or 1, 1-diphenylethyl;

p0057- A "heteroaryl radical" represents a monocyclic or polycyclic group, condensed or not, optionally cationic, comprising from 5 to 22 members and from 1 to 6 heteroatoms selected from nitrogen, oxygen, sulfur and at least one ring 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, phénooxazolyle, pyrazinyl, pyrazolyl, pyrilyle, pyrazoyltriazyle, pyridyl, pyridinoimidazolyle, pyrrolyl, quinolyl, tetrazolyl, thiadiazolyl, thiazolyl, thiazolopyridinyl, thiazoylimidazolyle, thiopyrylyle, triazolyl, xanthylyle and its ammonium salt;

p0058- A radical "diheteroarylalkyl" represents a group comprising, on the same carbon atom of an alkyl group, two heteroaryl groups, which are identical or different, such as difurylmethyl, 1, 1-difurylethyl, dipyrrolylmethyl dithienylmethyl;

p0059- A "cyclic group" is a non-aromatic cycloalkyl, mono- or polycyclic, condensed or not, containing from 5 to 22 carbon atoms, which may contain 1 or more unsaturations; particularly the cyclic radical is a cyclohexyl;

p0060- A radical "sterically hindered cyclic group" is a cyclic radical, aromatic or nonaromatic, substituted or unsubstituted, hindered by steric effect or stress, comprising 6 to 14 members, which may be bridged by way of sterically hindered radicals, bicyclo include [1.1.0] butane, the mésytyles such as 1, 3,5-triméthylpnényle, 1, 3,5-triterbutylphényle, 1, 3,5-isobutylphenyl, 1, 3,5-trimétylsillylphényle and adamantyl ;

p0061- A "heterocyclic group" is a non-aromatic radical mono- or polycyclic, condensed or not, containing from 5 to 22 members and having from 1 to 6 heteroatoms selected from nitrogen, oxygen, sulfur and selenium ;

p0062- An "alkyl group" is a hydrocarbon radical C₁-C₁₆Linear or branched, preferably C₁-C₈ ;

p0063- The expression "optionally substituted" assigned to the alkyl radical implies that said alkyl radical may be substituted by one or more radicals chosen from the radicals: i) hydroxy, ii) alkoxy, C₁-C₄Iii) acylamino, iv) amino optionally substituted by one or two alkyl radicals, identical or different C₁-C₄, Said alkyl radicals possibly forming with the nitrogen atom carrying them, a heterocycle comprising from 5 to 7 members, optionally comprising another heteroatom identical to or different from nitrogen; - A "alkoxy radical" is an alkyl-oxy radical or alkyl-O- in which alkyl is a hydrocarbon radical, linear or branched C₁-C₁₆ preferably C₁-cs;

p0064- A "alkylthio" is an alkyl-S- radical for which the alkyl radical is a hydrocarbon radical, linear or branched C₁-C₁₆ preferably C₁-cs; - The limits delimiting the extent of a range of values ​​are included in this range;

p0065- An "organic or mineral acid salt" is more particularly chosen from a salt derived from i) hydrochloric acid HCl, ii) hydrobromic acid HBr, iii) sulfuric acid H₂SO₄, Iv) alkylsulfonic acids: AIk-S (O)₂OH such as methylsulphonic acid and ethylsulphonic acid; v) arylsulfonic acids: Ar-S (O)₂OH such as benzenesulfonic and toluenesulfonic acid; vi) citric acid; vii) succinic acid; viii) tartaric acid; ix) lactic acid, x) of alcoxysulfiniques acids: Alk-OS (O) OH such as from methoxysulfinic acid and ethoxysulfinic acid; xi) of aryloxysulphinic acids such as acid tolueneoxysulphinic and phenoxysulphinic acid; xii) phosphoric acid H₃PO₄; xiii) of acetic acid CH₃COOH; xiv) of triflic acid CF₃SO₃H xv) tetrafluoroboric acid HBF₄ ;

p0066- A "against anionic ion" is an anion or an anionic group associated with a cationic charge of the dye; more particularly against the anionic ion is selected from: i) halides such as chloride or bromide; ii) nitrates; iii) sulfonates, including the C₁-C₆ alkylsulphonates: Alk-S (O)₂O^" such as methyl sulfonate or mesylate and ethyl sulfonate; 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)^" such as méthysulfate and ethylsulfate; x) arylsulfates: Ar-OS (O)^" such as benzenesulfate and toluenesulfate; xi) alcoxysulfates: Alk-OS (O)₂O^" such as methoxy sulphate and ethoxy; xii) aryloxysulfates: Ar-OS (O)₂O^"Xiii) phosphate; xiv) acetate; xv) triflate; and xvi) borates such as tetrafluoroborate.

p0067Fluorescent dyes of formula (I) or (II) are compounds capable of absorbing in the UV or visible radiation at a wavelength λ_atbs between 250 and 700 nm and capable of réémettrent in the visible range at a transmission wavelength λ_em between 400 and 700 nm. Preferably the fluorescent compounds of formula (I) or (II) are dyes capable of absorbing in the visible, λ_atbs between 400 and 700 nm and re-emitting in the visible, λ_em between 500 and 650 nm. More particularly the fluorescent dyes are dyes capable of absorbing at a wavelength λ_atbs between 420 nm and 550 nm and re-emitting in the visible range at a wavelength λ_em between 550 and 620 nm.

p0068A specific embodiment relates to fluorescent dyes of formula (I) or (II) according to SY where Y is a hydrogen atom, or an alkali metal. Preferably Y is hydrogen.

p0069The fluorescent compounds of the invention of formula (II) contain an SY function which may be in the covalent form -S-Y or -S ionic^" Y⁺ depending on the nature of Y and of the pH of the medium.

p0070According to another embodiment of the invention, in formula (II) above, Y is a protecting group known by the skilled person such as those described in the books "Protective Groups in Organic Synthesis", TW Greene, John Willey &amp; Sons ed, NY, 1981, pp.193-217. "Protecting Groups" P. Kocienski, Thieme, 3^th ed., 2005, c. 5.

p0071Especially when Y represents a group protecting the thiol function, Y is selected from the following radicals:

p0072• (-C₄) Alkylcarbonyl;

p0073• (C-rC₄) Alkylthiocarbonyl;

p0074• (-C₄) Alkoxycarbonyl;

p0075• (C-τC₄) Alkoxythiocarbonyl; • (-C₄) Alkylthio-thiocarbonyl;

p0076• (di) (C₁-C₄) (Alkyl) aminocarbonyl;

p0077• (di) (-C₄) (Alkyl) aminothiocarbonyl;

p0078• arylcarbonyl as phenylcarbonyl;

p0079• aryloxycarbonyl; • aryl (Ci-C₄) Alkcoxycarbonyle;

p0080• (di) (-C₄) (Alkyl) aminocarbonyl as dimethylaminocarbonyl;

p0081• (-C₄) (Alkyl) arylaminocarbonyl;

p0082• carboxyl;

p0083• SO₃^" ; M⁺ with M⁺ representing an alkali metal such as sodium or potassium, or else M 'of formula (II) and M⁺ are absent;

p0084• optionally substituted aryl such as phenyl, dibenzosuberyl, or 1, 3,5-cycloheptatrienyl,

p0085• optionally substituted heteroaryl; including the cationic or noncationic heteroaryl comprising from 1 to 4 heteroatoms: i) monocyclic 5-, 6- or 7-membered ring such as furanyl or furyl, pyrrolyl or pyrryl, thiophenyl or thienyl, pyrazolyl, oxazolyl, oxazolium, isoxazolyl, isoxazolium , thiazolyl, thiazolium, isothiazolyl, isothiazolium, 1, 2,4-triazolyl, 1, 2,4-triazolium, 1, 2,3-triazolyl, 1, 2,3-triazolium, 1, 2,4-oxazolyl, 1 , 2,4-oxazolium, 1, 2,4-thiadiazolyl, 1, 2,4-thiadiazolium, pyrylium, thiopyridyl, pyridinium, pyrimidinyl, pyrimidinium, pyrazinyl, pyrazinium, pyridazinyl, pyridazinium, triazinyl, triazinium, tetrazinyl, tétrazinium, azepine , azépinium, oxazepinyl, oxazépinium, thiepinyl, thiépinium, imidazolyl, imidazolium; ii) bicyclic 8- to 11-membered ring such as indolyl, indolinium, benzoimidazolyl, benzoimidazolium benzoxazolyl, benzoxazolium, dihydrobenzoxazolinyle, benzothiazolyl, benzothiazolium pyridoimidazolyle, pyridoimidazolium, thiénocycloheptadiényle, these monocyclic or bicyclic groups being optionally substituted by one or more groups such as ( -C₄) Alkyl such as methyl, or polyhalo (C d-₄) Alkyl such as trifluoromethyl; iii) or tricyclic ABC:

p0086<img id="imgf000014_0001" he="17" wi="37" file="imgf000014_0001.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="no" /> wherein both rings A, C optionally comprise a heteroatom, and ring B is a 5-, 6 or 7-membered, particularly 6-membered and contains at least one heteroatom as piperidyl or pyranyl;

p0087• optionally substituted heterocycloalkyl, optionally cationic, the heterocycloalkyl group is especially a monocyclic saturated or partially saturated 5-, 6- or 7-membered ring comprising 1 to 4 heteroatoms selected from oxygen, sulfur and nitrogen, such as di / tetrahydrofuranyl, di / tetrahydrothiophenyl, di / tetrahydropyrrolyl, di / tetrahydropyranyl, di / tetra / hexahydrothiopyranyle, dihydropyridyl, piperazinyl, piperidinyl, tetramethylpiperidinyl, morpholinyl, di / tetra / hexahydroazepinyl di / tetrahydropyrimidinyl, these groups being optionally substituted by one or more groups as (C₁-C₄) Alkyl, oxo or thioxo; or heterocycle represents the following group:

p0088<img id="imgf000014_0002" he="30" wi="38" file="imgf000014_0002.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="no" /> wherein R '^c, R '^d, R '^e, R '^f, R '⁹ and R '^h, Identical or different, represent a hydrogen atom or a (C₁-C₄) Alkyl, or else two groups R '⁹ R '^hAnd / or R '^e R '^f form an oxo or thioxo, or else R '⁹ R '^e together form a cycloalkyl; and V represents an integer ranging between 1 and 3; preferably, R '^c to R '^h represent a hydrogen atom; and An^" is against ion;

p0089- Isothiouronium -C (NR '^cR '^d) = N⁺R '^eR '^f; Year^" R '^c, R '^d, R '^e and R '^f, Identical or different, represent a hydrogen atom or a (Ci-C₄) Alkyl; preferably, R '^c to R '^f represent a hydrogen atom; and An^" is against ion;

p0090- Isothiourea -C (NR '^cR '^d) = NR '^e ; R '^c, R '^d and R '^e, As defined above;

p0091• (di) aryl (-C₄) Alkyl optionally substituted such as 9-anthracenylmethyl, diphenylmethyl or phenylmethyl optionally substituted by one or more groups chosen in particular from (CrC₄) Alkyl, (-C₄) Alkoxy such as methoxy, hydroxy, (CrC₄) Alkylcarbonyl or (di) (-C₄) (Alkyl) amino such as dimethylamino;

p0092• (di) heteroaryl (-C₄) Akyle optionally substituted, the heteroaryl group is in particular cationic or non monocyclic having 5 or

p00936 members and 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, such as pyrrolyl, furanyl, thiophenyl, pyridyl, pyridyl N-oxide such as 4-pyridyl or 2-pyridyl-N- oxide, pyrylium, pyridinium or triazinyl optionally substituted by one or more groups such as alkyl especially methyl, preferably (di) heteroaryl (Ci-C₄) Akyle is (di) heteroarylmethyl or (di) heteroarylethyl;

p0094• CR¹R²R³ with R¹, R² and R³ identical or different, representing a halogen atom or a group selected from:

p0095- (C₁-C₄) Alkyl; - (C₁-C₄) Alkoxy;

p0096- Optionally substituted aryl such as phenyl optionally substituted with one or more groups such as (CrC₄) Alkyl, (C₁- C₄) Alkoxy, hydroxy;

p0097- Optionally substituted heteroaryl, such as thiophenyl, furanyl, pyrrolyl, pyranyl, pyridyl, optionally substituted by a group

p0098(dC₄) Alkyl;

p0099- P (Z¹) R '¹R '²R '³ R '¹And R '² identical or different, representing a hydroxyl, (CrC₄) Alkoxy or alkyl, R '³ represents a hydroxy or (-C₄) Alkoxy, and Z¹ represents an atom of oxygen or sulfur;

p0100• hindered cyclic such as adamantyl; and

p0101• alkoxy (-C₄) Alkyl optionally substituted such as methoxymethyl (MOM), ethoxyethyl (EOM) and isobutoxymethyl.

p0102According to a particular embodiment, the protected thiol fluorescent dyes of formula (II) comprise a group Y i) monocyclic heteroaryl of 5 or 6 membered aromatic, cationic comprising 1 to 4 heteroatoms selected 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, tétrazinium, oxazépinium, thiepinyl, thiépinium, imidazolium; ii) heteroaryl bicyclic 8-membered to 1 of 1 such as cationic indolinium, benzoimidazolium benzoxazolium, benzothiazolium, these monocyclic or bicyclic heteroaryl groups being optionally substituted by one or more groups such as alkyl like methyl, or polyhalo (Ci-C₄) Alkyl such as trifluoromethyl; iii) or heterocyclic:

p0103<img id="imgf000016_0001" he="30" wi="26" file="imgf000016_0001.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="no" /> wherein R '^c and R '^d, Identical or different, represent a hydrogen atom or a (Ci-C₄) Alkyl; preferably, R '^c to R '^d represent a (dC₄) Alkyl such as methyl; and An^" represents an against-ion.

p0104Y particularly represents a group selected 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, imidazolium and triazinium, benzoimidazolium benzoxazolium, benzothiazolium, these groups being optionally substituted by one or more groups (-C₄) Alkyl especially methyl.

p0105In particular the dye of formula (II) have a Y group which is an alkali metal or a protecting group such as: > (Ci-C₄) Alkylcarbonyl such as methylcarbonyl or ethylcarbonyl;

p0106> Arylcarbonyl as phenylcarbonyl;

p0107> (Ci-C₄) Alkoxycarbonyl;

p0108> Aryloxycarbonyl; > Aryl (-C₄) Alkoxycarbonyl;

p0109> (Di) (-C₄) (Alkyl) aminocarbonyl as dimethylaminocarbonyl;

p0110> (C₁-C₄) (Alkyl) arylaminocarbonyl;

p0111> Optionally substituted aryl such as phenyl;

p0112> Cationic monocyclic heteroaryl of 5, 6-membered ring such as pyrylium, pyridinium, pyrimidinium, pyrazinium, pyridazinium, triazinium, imidazolium; these groups being optionally substituted by one or more identical or different groups (-C₄) Alkyl such as methyl;

p0113> Cationic bicyclic heteroaryl 8 to 1 of 1 links including benzoimidazolium or benzoxazolium; these groups being optionally substituted by one or more identical or different groups (-C₄) Alkyl such as methyl;

p0114> Cationic heterocycle of formula below:

p0115<img id="imgf000017_0001" he="27" wi="26" file="imgf000017_0001.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="no" />

p0116> Isothiouronium -C (NH₂) = N⁺H₂, Year^"; > Isothiourea -C (NH₂) = NH;

p0117> SO₃ M⁺ with M⁺ with M⁺ representing an alkali metal such as sodium or potassium, or else M 'of formula (II) and M⁺ are absent.

p0118According to a particular embodiment of the invention, the fluorescent dyes of the invention are of formula (Ia) or (Ma), each having an ethylene group linking the pyridinium part to the phenyl at the ortho or para position or in positions

p01194-4 ', 4-2' and 2-4 ': <img id="imgf000018_0001" he="58" wi="150" file="imgf000018_0001.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="no" /> formula (Ia) and (IIa) with R, R₂, R₃, R₄, R₃, Rb, R ,, R ',, R₉, R '_g, Rh, R'H, m, n, Y, R ',, R'₂, R '₃, R ₄, R'a, R'b R ",, R" ,, R "_g, R "_g, R "_h, R "_h, M 'and n' are as defined above.

p0120Another embodiment of the invention relates disulfide dyes of formula (I) or (Ia) symmetrical ie R₃, Rb, R₉, R '_g, Rh, R'H, R₁₁ R'i. Ri> R2, R3, R₄T₃, M, n are equal to R '_at, R '_b, R "_g, R "_g, R "_h, R "_h, R ",, R" ,, R^{^}₁, R '₂, R '₃, R ₄T_b, M 'and n', respectively.

p0121Examples of thiol fluorescent dyes, mention may be made of the following dyes:

p0122<img id="imgf000018_0002" he="23" wi="121" file="imgf000018_0002.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="no" />

p0123<img id="imgf000018_0003" he="18" wi="142" file="imgf000018_0003.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="no" />

p0124<img id="imgf000018_0004" he="22" wi="129" file="imgf000018_0004.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="yes" /><img id="imgf000019_0001" he="211" wi="155" file="imgf000019_0001.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="no" /><img id="imgf000020_0001" he="23" wi="128" file="imgf000020_0001.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="no" />

p012516

p0126<img id="imgf000020_0002" he="21" wi="136" file="imgf000020_0002.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="yes" />

p012717

p0128<img id="imgf000020_0003" he="18" wi="143" file="imgf000020_0003.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="no" />

p012918

p0130<img id="imgf000020_0004" he="18" wi="128" file="imgf000020_0004.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="no" />

p013119

p0132<img id="imgf000020_0005" he="18" wi="133" file="imgf000020_0005.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="yes" />

p013320

p0134<img id="imgf000020_0006" he="16" wi="141" file="imgf000020_0006.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="yes" />

p013521

p0136<img id="imgf000020_0007" he="22" wi="128" file="imgf000020_0007.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="no" />

p013722 <img id="imgf000021_0001" he="21" wi="136" file="imgf000021_0001.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="no" />

p013823

p0139<img id="imgf000021_0002" he="18" wi="72" file="imgf000021_0002.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="no" />

p014024

p0141<img id="imgf000021_0003" he="23" wi="95" file="imgf000021_0003.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="no" />

p014225

p0143<img id="imgf000021_0004" he="17" wi="114" file="imgf000021_0004.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="no" />

p014426

p0145<img id="imgf000021_0005" he="18" wi="119" file="imgf000021_0005.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="no" />

p014627

p0147<img id="imgf000021_0006" he="26" wi="98" file="imgf000021_0006.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="no" />

p014828 M ', Year^", Identical or different, representing an anionic against ion.

p0149M 'and An^", Identical or different, represent in particular against an-ion such as halides, such as chloride or bromide; nitrates; sulfonates including the C-pCβ alkylsulfonates: AIk-S (O)₂O^" such as methyl sulfonate or mesylate and ethyl sulfonate; arylsulfonates: Ar-S (O)₂O^" such as benzenesulfonate and toluenesulfonate or tosylate; citrate; succinate; tartrate; lactate; sulphates: Alk-OS (O)^" such as methyl sulfate and ethyl sulfate; arylsulfates: Ar-OS (O)^" such as benzenesulfate and toluenesulfate; the alcoxysulfates: Alk-OS (O)₂O^" such as methoxy sulphate and ethoxy; aryloxysulfates the Ar-OS (O)₂O^", Phosphate; acetate; triflate; and borates such as tetrafluoroborate.

p0150Protected thiol dyes of formula (II) can be synthesized in two steps. The first step of preparing the thiol dye unprotected by the methods known to the skilled artisan such as "Thiols and organic Sulfides", "Thiocyanates and Isothiocyanates, organic," Ullmann's Encyclopedia, Wiley-VCH, Weinheim, 2005. And the second step of protecting the thiol function according to conventional methods known in the art to give the protected thiol dyes of formula (II). For example, to protect the thiol function -SH of the thiol dye methods of structures can be used "Protective Groups in Organic Synthesis", TW Greene, John Willey &amp; Sons ed, NY, 1981, pp.193-217. "Protecting Groups" P. Kocienski, Thieme, 3^th ed., 2005, c. 5.

p0151We demonstrate this method by the method comprising i) generating thiol fluorescent dyes by reduction of a fluorescent dye in two chromophores bearing a disulfide function -SS- such as (I) and ii) to be protected according to conventional methods said function thiol compounds (M ') to access the protected thiol fluorescent dyes of formula (M "):

p0152<img id="imgf000022_0001" he="57" wi="142" file="imgf000022_0001.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="no" /> with R₁, R₂, R₃, R₄, R₃, Rb, R₉, R '_g, Rh, R'H, R ,, R ',, T₃, M, n and M are as defined above and R represents a nucleofugic leaving group, such as mesylate, tosylate, triflate or halide, and Y 'represents a protecting group of the thiol function. Alternatively, one can react a protected thiol compound (b) with a protecting group Y 'as defined above, prepared according to the procedures described in references cited previously, said protected thiol compound comprising at least one nucleophilic function with a sufficient amount, preferably equimolar to a "reactive fluorescent chromophore" or a compound comprising such a "reactive fluorescent chromophore £ a). In other words (a) comprises a nucleofugic function to form a covalent bond as Σ can be summarized below:

p0153<img id="imgf000023_0001" he="51" wi="129" file="imgf000023_0001.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="no" /> with R₁, R₂, R₃, R₄, R₃, R_b, R₉, R '_g, Rh, R'H, R ,, R ',, Y', m, n and M are as defined above; 5Yω representing a nucleophilic amine group, such as oxygenated primary amine, hydroxyl, thiol; £ representing an electrophilic group containing a carbonyl, thiocarbonyl such as an acyl halide, acyl thiohalogénure, ester, thioester. It follows that Σ is a sequence of groups selected from -SO₂-, -O-, -S-, -N (R) -, -CO-, where R, represents a hydrogen atom, an alkyl radical -C₄Hydroxyalkyl, -C₄; or aryl (-C₄) Alkyl especially Σ represents a group selected from -C (O) -

p0154N (R) -, -C (O) -O-, -C (S) -O-, -C (O) -S-, -C (S) -S- or -C (S) -N ( R) -. Use may also be a thiol reagent Y-SH comprising a Y moiety, the nucleophilic SH group can react on the carbon atom alpha to the halogen carried by the fluorescent chromophore atom (a ') to give the fluorescent dye protected thiol of formula (II):

p0155<img id="imgf000023_0002" he="27" wi="122" file="imgf000023_0002.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="no" /> with R₁, R₂, R₃, R₄, R₃, R_b, R₉, R '_g, Rh, R'H, R, R ', T₃, Y, m, n and M 'are as defined above, and Hal representing a halogen atom nucleofugic such as bromine, iodine or chlorine.

p0156We can also use a thioacid (α) (e.g., thioacetic acid) which will act on halide carried by the fluorescent chromophore [a ^:

p0157<img id="imgf000024_0001" he="29" wi="135" file="imgf000024_0001.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="no" /> with R₁, R₂R 3, R₄, R_at, Rb, R, R '_g, Rh, R'H, R, R ', rn, n, T₃, M 'are as defined above and R' represents a group (d-CβJalkyle.

p0158More particularly may be substituted by a nucleofugic leaving group a thiourea group (S = C (NRR) NRR) for generating the isothiouroniums. For example, if the thiourea group is a thioimidazolinium (β), the reaction scheme is as follows:

p0159<img id="imgf000024_0002" he="34" wi="132" file="imgf000024_0002.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="no" /> with R₁, R₂, R₃, R₄, R₃, R_b, R'c, R'd, R₉, R '_g, R_h, R'H R, R ',, m, n, T₃, Year^" and M 'are as defined above.

p0160An alternative is to use instead of the halide comprising the fluorescent chromophore [a]) a chromophore comprising another type nucleofuge as tosylate, mesylate.

p0161According to another variant it is possible to generate an imidazoline intermediate from the halide comprising the fluorescent chromophore (a ') and a thioimidazoline (b') to yield, after alkylation with an R-Gp reagent with R representing an alkyl group and gp a leaving group such as halogen such as chlorine, bromine, iodine, or a mesylate or tosylate group, to yield the dye of formula (M ""). <img id="imgf000025_0001" he="82" wi="130" file="imgf000025_0001.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="no" />

p0162May also be substituted by a nucleofugic leaving group thiosulfate salts (eg sodium thiosulfate or potassium) to generate the Bunte salts (-SSO₃^", N / A⁺ or K⁺):

p0163<img id="imgf000025_0002" he="24" wi="132" file="imgf000025_0002.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="no" /> with R, R₂R 3, R₄, R_at, Rb, R, R '_g, Rh, R'H, R, R ', rn, n, T₃, M 'are as defined above and M⁺ representing an alkali metal such as sodium or potassium.

p0164According to another possibility, certain protected thiol fluorescent dyes (M ") can be obtained by reacting a thiol compound with a compound carrying a carbonyl function or nucleofugic type acyl halide £ d) reacted with a chromophore fluorescent holder of a nucleophilic function (ç), primary or secondary amine-type:

p0165<img id="imgf000025_0003" he="24" wi="133" file="imgf000025_0003.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="no" /> with R₁ , R₂, R₃, R₄, R₃, Rb, R₉, R '_g, Rh, R'H, R ,, R ',, T₃, Y, m, n, M ', and 5VM (M ") such defined above and ¹E represents an electrophilic group containing a carbonyl, thiocarbonyl such as an acyl halide, acyl thiohalogénure, ester, thioester. It follows that Σ is a sequence of groups selected from -SO₂-, -O-, -S-, -N (R) -, -CO-, with R Represented a hydrogen atom, an alkyl radical C₁-C₄Hydroxyalkyl, C₁-C₄; or aryl (C₁-C₄) Alkyl especially Σ represents a group selected from -N (R) -C (O) -, -0-C (O) -, -0-C (S) -, -SC (O) -, - SC ( S) - or -N (R) -C (S) -.

p0166An alternative is to use a thiolactone can undergo nucleophilic attack of an amino group carried by the chromophore styrylpyridinium (c ') to yield the thiol fluorescent dye (II'_at) Which may either be protected or be metallated to give respectively dyes (II "_at) and M"_atputs) as illustrated in the following diagram:

p0167<img id="imgf000026_0001" he="76" wi="152" file="imgf000026_0001.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="no" />

p0168According to another possibility, the protected thiol fluorescent dyes of formula (II) can be obtained by reacting a compound comprising a thiol group protected by a group Y, and a hydroxy group activated in advance nucleofugic leaving group CQ £, for instance mesylate, tosylate, triflate or halide with a fluorescent chromophore (ç |) bearing a nucleophilic functional primary amine when R_b represents a hydrogen atom, or secondary amine. R₃R₄) - SY (H)

p0169<img id="imgf000027_0001" he="25" wi="87" file="imgf000027_0001.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="no" />

p0170with R₁, R₂, R₃, R₄, R₃, Rb, R₉, R '_g, Rh, R'n, R., R., T₃, Y, m, n, and M 'are as defined above and E represents a group nucleofugic such as mesylate, tosylate, triflate or halide.

p0171According to another possibility, the thiol fluorescent dyes of formula (II) according to the invention can be obtained by reacting a compound having a protected thiol group and an electrophilic group (f) with a compound comprising a nucleophilic group. For example, one can condense an aldehyde or ketone when G represents an oxygen atom with an "activated methylene" such as alkylpyπdinium £ e) for generating an ethylene bond> C = C <. This reaction is commonly known condensation "Knoevenagel". By "activated methylenes" it implies those mentioned for example in patent DE19951134 particularly there may be mentioned 1, 2-dialkylpyridinium and in particular the 1, 2-dimethylpyridinium:

p0172<img id="imgf000027_0002" he="59" wi="147" file="imgf000027_0002.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="no" />

p0173with R, R₂, R₃, R₄, R_at, Rb, R, R 'g, Rh, R'H, R', T₃, Y, m, n, M 'as defined above and G is oxygen, sulfur or a group NR "with R" representing a hydrogen atom or an alkyl group.

p0174Another variant of this reaction scheme is to achieve the coupling reaction of "Knoevenagel" ie subsequently from the intermediate £ Q_> I^e R'NH amino group can react with one equivalent of reagent E - (CR₃R₄I for lead to [Q which itself can react with a thiol derivative Y'SH to give the intermediate aldehyde [Q. This intermediate can undergo the condensation reaction "Knoevenagel" with alkylpyridinium £ e] to yield the protected thiol fluorescent dye (M ").

p0175<img id="imgf000028_0001" he="201" wi="151" file="imgf000028_0001.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="no" /> with R ', R, R₂, R₃, R₄, R₃, Rb, R₉, R '_g, Rh, R'H, R ,, R ',, ¹E, m, n, Y ', and M' as defined, and Σ represents in particular a N (R) -C (O) -, or -N (R) -C (S) -.

p0176Reference may be made to the book Advanced Organic Chemistry, "Reactions, Mechanisms and Structures", J. March, 4^th Ed, John Willey &amp; Sons, 1992, or TW Greene "Protective Groups in Organic Synthesis" for more details on the operating conditions used in the processes mentioned above.

p0177The thiol fluorescent dyes formed can be converted into protected thiol fluorescent dyes -SY 'by the -SH thiol protection using standard protecting groups. Thiols fluorescent dyes can also beings metallated using conventional methods known to those skilled in the art such as those described in Advanced Organic Chemistry, "Reactions, Mechanisms and Structures", J. March, 4^th Ed, John Willey &amp; Sons, NY, 1992.

p0178The protected thiol dyes can be deprotected by conventional routes such as those described in the books "Protective Groups in Organic Synthesis", TW Greene, John Willey &amp; Sons ed, NY., 1981; "Protecting Groups" P. Kocienski, Thieme, 3^th ed., 2005.

p0179Departures reagents are commercially available or accessible by conventional routes known to the skilled person. For example to synthesize the fluorescent dye chromophores two bearing a disulfide function -SS- (I '), can be from a reactant difunctionalized (k), comprising position 1 year a nucleofugic group GR with R representing a group (CτC₄) Alkyl, mesylate, tosylate, or triflate and G is an oxygen or sulfur atom or a halogen such as fluorine, chlorine, iodine, and comprising 2 or 4 position an electrophilic aldehyde group or thioaldéyde. Two equivalents of this reagent may react with the diamine-dialkyl disulfide (|) to yield, after condensation diketone / thioalcétone disulfide (m) can be condensed with two equivalents alkylpyridinium (e) to form the compound [T). <img id="imgf000030_0001" he="75" wi="151" file="imgf000030_0001.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="no" />

p0180Reference may be made to the book Advanced Organic Chemistry, J. March, 4^th Ed, John Willey &amp; Sons, 1992, or TW Greene "Protective Groups in Organic Synthesis" for more details on the operating conditions used in the processes mentioned above.

p0181The unsymmetrical disulfide dyes of formula (I) can be synthesized in one step by reacting a thiol fluorescent dye unprotected with a protected thiol fluorescent dye to form the disulphide dye of formula (I).

p0182<img id="imgf000030_0002" he="24" wi="150" file="imgf000030_0002.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="no" />

p0183<img id="imgf000030_0003" he="23" wi="135" file="imgf000030_0003.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="no" /> with R₃, R '_at> Rb> Rg R'bi> R'gi R "g> R" gi i Rh R'hi R "h> R" hi Rii R'ii R "i> R" R 'i ii R21

p0184R '₂, R₃, R '₃, R₄, R ₄ m, m ', n, n', T_atT_b and M 'are as defined above; Y 'represents a protective group of thiol.

p0185The composition of the invention contains at least one fluorescent dye of formula

p0186(I) or (II). Furthermore the presence of at least one thiol fluorescent dye of formula (I), the composition of the invention may also contain a reducing agent. this agent reducing agent may be chosen from thiols such as cysteine, homocysteine, thiolactic acid, the salts of these thiols, phosphines, bisulphite, sulphites, thioglycolic acid and its esters, in particular monothioglycolate glycerol and thioglycerol. This reducing agent may also be selected from borohydrides and derivatives thereof, such as salts of borohydride, cyanoborohydride, triacetoxy borohydride, trimethoxy borohydride: sodium, lithium, potassium, calcium salts, quaternary ammonium salts (tetramethylammonium, tetraethylammonium, tetra n-butylammonium bromide, benzyltriethyl-ammonium); the catéchol- borane. The dye composition according to the invention generally contains a quantity of fluorescent dyes of formula (I) or (II) of between 0.001 and 50% based on 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. The dye composition may also contain additional direct dyes. These direct dyes are chosen, for example nitrobenzene direct dyes, neutral, acidic or cationic neutral azo direct dyes, acid or cationic tetraazapentamethine dyes, quinone dyes and in particular anthraquinone, acidic or cationic, direct dyes, azine , triarylmethane direct dyes, direct dyes indoamine and natural direct dyes.

p0187Among the natural direct dyes include lawsone, juglone, alizarin, purpurin, carminic acid, kermesic acid purpurogallin, protocatechaldehyde, indigo, isatin, curcumin, spinulosin, apigenidin. One can also use extracts or decoctions containing these natural dyes and in particular poultices or extracts based on henna.

p0188The dye composition may contain one or more oxidation bases and / or one or more couplers conventionally used for dyeing keratin fibers. Among 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

p0189Among these couplers, mention may be made of meta-phenylenediamines, meta-aminophenols, meta-diphenols, naphthalene couplers, couplers heterocyclic and their addition salts.

p0190The coupler or couplers are each present in an amount between 0.001 and 10% by weight of the total weight of the dyeing composition, preferably between 0.005 and 6%. The oxidation of bases present in the dye composition can be present in an amount ranging from 0.001 to 10% by weight of the total weight of the dyeing composition, preferably between 0.005 and 6% by weight.

p0191In general, the addition salts of the oxidation bases and couplers used in the context of the invention are chosen from the addition salts with an acid such as hydrochlorides, hydrobromides, sulphates, citrates, succinates, tartrates, lactates, tosylates, benzenesulfonates, phosphates and acetates, and the addition salts with a base, such as hydroxides of alkali metal such as sodium, potassium, ammonia, amines or alkanolamines. The medium suitable for dyeing, also called dye support, is a cosmetic medium consisting of water or a mixture of water and at least one organic solvent. As organic solvent, there may be mentioned are lower alcohols -C₄, Such as ethanol and isopropanol; polyols and polyol ethers such as 2-butoxyethanol, propylene glycol, monomethyl ether of propylene glycol, monoethyl ether and monomethyl ether, and aromatic alcohols such as benzyl alcohol or phenoxyethanol, and mixtures thereof.

p0192The solvents when 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.

p0193The dye composition may also contain various adjuvants conventionally used in compositions for dyeing the hair, such as anionic, cationic, nonionic, amphoteric, zwitterionic surfactants, anionic, cationic, nonionic, amphoteric, zwitterionic or mixtures thereof, thickening agents, inorganic or organic, and associative thickeners anionic, cationic, nonionic and amphoteric polymers, antioxidants, penetrants, sequestering agents, fragrances, buffers, dispersing agents, agents packaging such as for example, volatile or nonvolatile silicones, modified or not, such as amino silicones, film-forming agents, ceramides, preservatives, opacifiers, or conductive polymers.

p0194The above adjuvants are generally present in an amount for each ranging from 0.01 to 20% by weight relative to the weight of the composition.

p0195Of course, the man of the art care to select this or these optional additional compounds such that the advantageous properties intrinsically associated with the dye composition according to the invention are not, or not substantially, impaired by the additions envisaged. The pH of the dye composition is generally between 3 and 14 approximately, and preferably between approximately 1 to 1 5. It can be adjusted to the desired value using acidifying or alkalizing agents usually used for dyeing keratin fibers, or alternatively using standard buffer systems.

p0196Among the acidifying agents, mention may, for example, the inorganic or organic acids such as hydrochloric acid, orthophosphoric acid, sulfuric acid, carboxylic acids such as acetic acid, tartaric acid, citric acid, lactic acid, and sulphonic acids.

p0197Among the alkalizing agents include, for example, ammonia, alkaline carbonates, alkanolamines such as mono-, di- and triethanolamine and derivatives thereof, sodium or potassium hydroxides and compounds formula (γ) below:

p0198% '/ ³²

p0199N - W₃-NOT

p0200R₃4 ^Ra3 (_γ) Wherein W₃ is a propylene residue optionally substituted with a hydroxyl group or an alkyl radical -C₄ ; R_ati, R_a2, R₃3 and R_a4, Identical or different, represent a hydrogen atom, an alkyl radical C₁-C₄ or hydroxy C₁-C₄.

p0201The dye composition may be in various forms, such as in liquid, cream, gel, or in any other form suitable for dyeing keratin fibers, especially the hair. The staining method of the invention consists in applying the composition of the invention to the keratin materials, especially keratin fibers, including human such as the hair, especially dark hair, the dyeing composition of the invention comprising at least one fluorescent dye of formula (I) or (II).

p0202According to a particular embodiment in the method of the invention a reducing agent can be applied as a pretreatment before application of the composition containing at least one fluorescent dye of formula (I) or (II).

p0203This reducing agent may be chosen from thiols such as cysteine, homocysteine, thiolactic acid, the salts of these thiols, phosphines, bisulphite, sulphites, thioglycolic acid and its esters, in particular glycerol monothioglycolate, and thioglycerol. This reducing agent may also be selected from borohydrides and derivatives thereof, such as salts of borohydride, cyanoborohydride, triacetoxyborohydride of trimethoxyborohydride: sodium, lithium, potassium, calcium salts, quaternary ammonium salts (tetramethylammonium, tetraethylammonium, tetra-n butylammonium, benzyltriethylammonium); catecholborane.

p0204This pretreatment may be of short duration, in particular 0.1 second to 30 minutes, preferably 1 minute to 15 minutes with a reducing agent as mentioned previously.

p0205According 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.

p0206When the fluorescent dye (I) or (II) comprises a protecting group Y of the thiol function, the method of the invention may be preceded by a deprotection step aimed at restoring in-situ the SH function.

p0207For example it is possible to deprotect the SY function Y protecting group by adjusting the pH as follows:

p0208<img id="imgf000034_0001" he="47" wi="152" file="imgf000034_0001.tif" img-format="tif" img-content="table" orientation="portrait" inline="no" />

p0209<img id="imgf000035_0001" he="50" wi="152" file="imgf000035_0001.tif" img-format="tif" img-content="table" orientation="portrait" inline="yes" />

p0210The deprotection step can also be performed during a hair pretreatment step as for example, the reducing pretreatment of the hair.

p0211According 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.

p0212Alternatively, the reducing agent is added to the dye composition containing at least one fluorescent dye (I) or (II) at the time of use. According to another variant, the reducing agent is applied by post-treatment, after application of the composition containing at least one fluorescent dye (I) or (II). The duration of post-treatment with the reducing agent may be short, for example from 0.1 second to 30 minutes, preferably 1 minute to 15 minutes, with a reducing agent as described above. In a particular embodiment the reducing agent is a thiol agent or borohydride as described above.

p0213A particular embodiment of the invention relates to a method wherein the fluorescent dye of formula (I) or (II) may be applied directly to the hair without reducing agents, free of reducing pretreatment or reducing aftertreatment.

p0214Treatment with an oxidizing agent may optionally be combined. We can use any type of conventional oxidizing agent in the field. Thus, it can be chosen from hydrogen peroxide, urea peroxide, alkali metal bromates, persalts such as perborates and persulphates, and enzymes, among which mention may be made peroxidases, oxido 2-electron such as uricase and 4-electron oxygenases such as laccases. The use of hydrogen peroxide is particularly preferred.

p0215This oxidizing agent may be applied to the fibers before or after applying the composition containing at least one fluorescent dye of formula (I) or (II). The application of the dye composition according to the invention is generally carried out at room temperature. It may however be carried out at temperatures ranging from 20 to 180 ° C.

p0216The invention also relates to a multi-compartment device or "kit" 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 the keratin materials.

p0217One of these compartments may also contain one or more other dyes direct dye or oxidation dye.

p0218It also relates to a multi-compartment device 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.

p0219Another variant relates to a device with several compartment or "kit" for dyeing comprising a first compartment containing a composition with at least one protected fluorescent dye of formula (II) and a second compartment comprising a composition containing a deprotecting agent such that a base. Each of the devices mentioned above may be equipped with a means for applying to the hair the desired mixture, for example such as the devices described in patent FR 2 586 913.

p0220The following examples serve to illustrate the invention without being limiting in nature. Fluorescent dyes of the examples below were fully characterized by spectroscopic and spectrometric methods conventional.

EXAMPLES

SYNTHESIS EXAMPLES

p0223EXAMPLE 1 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]

p0224<img id="imgf000037_0001" he="23" wi="121" file="imgf000037_0001.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="no" />

p0225[1]

p0226Synthetic Scheme

p0227V / V_P

p0228HN ^ - N \ \

p0229<img id="imgf000037_0002" he="89" wi="121" file="imgf000037_0002.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="no" />

p0230[1]

p0231Step 1: Synthesis of 4- {methyl [3- (methylamino) propyl] amino} benzaldehyde

p02328.64 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. 1 1 9 mL of 1, 3-bis (methylamino) propane are added dropwise to the reaction mixture stirred and heated to 110 ° C for 3 days. The reaction mixture was concentrated and 54 g of collected oil. Step 2: Synthesis of acetate, 1-methyl-4 - [(E) -2- (4- {methyl [3- (methylamino) - propyl] amino} phenyl) vinyl] pyridinium

p023325 g of 4- {methyl [3- (methylamino) propyl] amino} benzaldehyde dissolved in 30 ml of isopropanol and 10.9 mL of pyrrolidine were stirred at ambient temperature for 10 min. 7.6 mL of acetic acid are added to the reaction mixture stirred at 20 ° C for 20 min. 26.55 g of methyl 1, 4-dimethylpyridinium diluted in 20 mL of isopropanol are added. The reaction medium is stirred at room temperature for 5 days. The resulting mixture was extracted 3 times with dichloromethane (DCM), concentrated and purified by liquid water / butanol chromatography. After concentration in vacuo of the pure fractions, 3.4 g of red powder are collected.

p0234Step 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

p02351, 63 g of acetate of 1-methyl-4 - [(E) -2- (4- {methyl [3- (methylamino) propyl] amino} phenyl) - vinyl] pyridinium bromide are dissolved in 5 ml of acetonitrile (ACN). 600 .mu.l of diisopropylethylamine (DIPEA), 420 mg of 3,3'-dithiopropanoïque acid and 1, 09 g of hexafluorophosphate (1H-1, 2,3-benzotriazol-1-yloxy) (tripyrrolidin-1-yl ) - phosphonium added to the mixture. After 24 h stirring at room temperature, the mixture was concentrated and purified by chromatography on silica gel (reverse phase grafted C₁₈ ; eluant water / ACN / 0.1% trifluoroacetic acid). The pure fractions were combined and neutralized by adding sodium hydrogencarbonate, concentrated in vacuo and the solid obtained is taken up in acetone / ACN. After filtration, solvent evaporation leads to a red solid mass of 1, 77 g. The analyzes indicate that the product conforms to the expected structure. The counters An- ions consist of a mixture of trifluoroacetate and hydrogen. LCMS: positive ions m / z = 383, 256 and 192 respectively corresponding to [M / 2]²⁺[M + H]³⁺ and [M + 2H]⁴⁺. λ_max 468 nm. EXAMPLE 2 Synthesis of the salt of 1-methyl-4 - {(E) -2- [4- (methyl {3- [methyl (3- sulfanylpropanoyl) -amino] propyl} amino) phenyl] vinyl} pyridinium [2]

p0236<img id="imgf000039_0001" he="13" wi="62" file="imgf000039_0001.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="no" />

p0237Year^"

p0238[2]

p0239Synthetic Scheme

p0240<img id="imgf000039_0002" he="69" wi="121" file="imgf000039_0002.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="no" />

p0241[2] = An- mixture of TFA and HCO₃-

p0242Step 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 ]

p024360 mg of 1-methyl-4 salt - {(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; 2eq. hydrate hydrochloride of 3- [bis (2-carboxyethyl) phosphino] propanoic acid dissolved in 1 ml of water and 4 eq of sodium bicarbonate in solution in 1 ml of water are added to the mixture. After 30 minutes stirring at 40 ° C under an inert atmosphere, the analyzes indicate that the mixture contains very predominantly the expected product [2]. LC-MS analysis: LC-DAD (400-700 nm) Column: Waters XTerra MS C18 5 .mu.m (4.6 x 50) mm Mobile Phase: A: water + 0.1% formic acid / B: ACN linear gradient: T (min) A % /% B: 0 min 95/5; 8 min 0/100 Flow rate: 1 mL / min.

p0244Detection: UV LED Strip λ = 400-700nm MS (ESI +): corresponds to the mass peak of monocation the expected product [2]

EXAMPLES OF COLOUR

p0246Example 1: color process - compound [1]

p0247Preparation of a composition A

p0248disulphide dye [1] 10^"3 mol%

p0249Benzyl Alcohol 4 g

p02506 g polyethylene glycol 6EO

p0251Hydroxyethylcellulose 0.7 g

p0252Alkylpolyglycoside in aqueous solution at 65% AS 4.5 g

p0253Demineralized water qs 100 g

p0254Preparing a composition B

p0255Thioglycolic acid 1M

p0256Sodium hydroxide qs pH 8.5

p0257Demineralized water qs 100 g

p0258At the time of use, mix compositions A (9 mL) and B (1 mL) and then apply the mixture to a lock of 1 g of dark hair (tone height 4) for 30 minutes at room temperature (the locks are turned over and reimpregnated after 15 minutes).

p0259After rinsing with running water and drying, there is a thinning of hair thus treated: the lock of tone height 4 has become visually lighter than untreated control locks.

p0260Example 2: staining method with compound [2]

p026110 ml fresh solution of the compound [2] in the synthesis example are applied to a 1 g lock of hair of tone height 4 placed at the bottom of a bowl for 30 minutes at room temperature (the locks are turned over and re-treated after 15 minutes).

p0262The locks were then rinsed with running water and dried. After staining, the wick of tone height 4 has become visually lighter than untreated control locks. Persistence vis-à-vis successive shampooing:

p0263The locks thus treated are divided into two, one half is subjected to 5 successive shampooing according to a cycle which includes the wetting of the locks with water, washing with a conventional shampoo, rinsing with water followed by drying.

p0264visual observations

p0265In shampoos, there is no visible bleeding, the shampoo foam and the rinsing water are not colored

p0266The observed color is preserved and the lightening effect remains visible on the height of your hair so treated 4.

p0267Results in the L^*at^*b^* :

p0268The color of the locks before and after the 5 washes was evaluated in the L^*at^*b^* using a MINOLTA CM 2600D spectrophotometer ® (Illuminant D65).

p0269In this L^* at^* b^*, L^* represents the brightness, a^* indicates the axis of green / red color and b^* axis blue / yellow color. The higher the value of L, the higher the color lighter or less intense. Conversely, the more the value of L is small, the color is dark or intense. Plus the value of a^* the higher the grade is red and the value of b^* the higher the grade is yellow.

p0270The change in coloring between the strands of hair HT4, stained and washed are measured by (.DELTA.E) using the following equation:

p0271Δ E = V (L * - L₀ *)² + (A * - a₀ *)² + (B * - b₀ *)²

p0272In this equation, L^*, at^* and B^* represent the values ​​measured before coloring and L₀^*, ao^* and bo^* represent the values ​​measured before coloring (or shampoo).

p0273Plus the value of .DELTA.E, the greater the difference in color between HT4 locks and dyed locks is important.

p0274<img id="imgf000041_0001" he="30" wi="152" file="imgf000041_0001.tif" img-format="tif" img-content="table" orientation="portrait" inline="yes" /> The results of the above table show that the color changes very little after 5 shampoos. Thus, the coloring and the lightening effect on the hair remains virtually unchanged, showing a very good resistance to shampoos dyes of the invention.

p0275Reflectance Results:

p0276lightening effectiveness of the compositions according to the invention and their vis-a-vis remanence successive shampoos were expressed in terms of the reflectance of the hair. These reflectances are compared to the untreated reflectance of a lock of hair of tone height TH4.

p0277The reflectance is measured using a MINOLTA-spectrophotocolorimeter device KONIKA ®, CM 260Od and after irradiation of the hair with visible light in the wavelength range from 400 to 700 nanometers.

p0278Reflectance of the locks treated with the compound one application and after 5 shampoos

p0279January 1 -5 shampoos

p0280<img id="imgf000042_0001" he="41" wi="120" file="imgf000042_0001.tif" img-format="tif" img-content="drawing" orientation="portrait" inline="no" /> oooooooooooooooo

p0281CM O ^ t ^ tO CM O CO CO O CM tO t ^ O ^ t tO CO ^ t ^ t ^ t ^ t t LO LO LO LO LO tO tO tO tO tO h-

p0282Wavelength (nm)

p0283We first note 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 brighter.

p0284In addition, the results show that the reflectance of the locks of hair of tone height 4 treated with the composition of the invention change very little after 5 shampoos. Thus, the coloring and the lightening effect on the hair remains virtually unchanged, showing a very good resistance to shampoos dyes of the invention.