Process for preparing (hetero)aromatic compounds bearing a hydroxyethylamino group from (DI)(ALKYL)glycolaldehyde dimer and (hetero)aromatic compounds bearing a nitro(SO) group

Abstract

The invention relates to a process for preparing (hetero)aromatic compounds substituted with a hydroxyethylamino group (B) from aromatic compounds bearing a nitro(so) group (A) in the presence i) of (di)(alkyl)glycolaldehyde dimer and ii) in a reduction medium, it being understood that step i) and ii) are performed simultaneously or as a "one pot" reaction.

Description

[0001] DESCRIPTION

[0002] TITLE: Process for preparing (hetero)aromatic compounds bearing a hydroxyethylamino group from (di)(alkyl)glycolaldehyde dimer and (hetero)aromatic compounds bearing a nitro(so) group

[0003] The invention relates to a process for preparing (hetero)aromatic compounds substituted with a hydroxyethylamino group (B) from aromatic compounds bearing a nitro(so) group (A) in the presence i) of (di)(alkyl)glycolaldehyde dimer and ii) in a reduction medium, it being understood that step i) and ii) are performed simultaneously or as a “one pot” reaction.

[0004] Many people have sought for a long time to modify the color of their hair and in particular to mask their gray hair.

[0005] In the field of dyeing hair keratin fibers, in particular human keratin fibers, it is already known practice to dye hair keratin fibers via various techniques using direct dyes or pigments for non-permanent dyeing, or dye precursors for permanent dyeing.

[0006] There are essentially three types of process for dyeing the hair:

[0007] a) “permanent” dyeing, the function of which is to afford a substantial modification to the natural color and which uses oxidation dyes which penetrate into the hair fiber and form the dye via an oxidative condensation process;

[0008] b) non-permanent, semi-permanent or direct dyeing, which does not use the oxidative condensation process and withstands four or five shampoo washes; it consists in dyeing keratin fibers with dye compositions containing direct dyes;

[0009] c) temporary dyeing, which gives rise to a modification of the natural color of the head of hair which lasts from one shampoo wash to the next, and which serves to enhance or correct a shade that has already been obtained. It may also be likened to a “makeup” process. It is thus known practice to dye keratin fibers, in particular human keratin fibers such as the hair, to obtain “permanent” dyeing with dye compositions containing oxidation dye precursors, notably oxidation bases, such as ortho- or para-phenylenediamines, ortho- or para-aminophenols, or heterocyclic compounds such as pyrazoles, pyrazolinones or pyrazolopyridines. These oxidation bases are colorless or weakly colored compounds which, in combination with oxidizing products, can give rise, by an oxidative condensation process, to colored compounds.It is also possible to vary the shades obtained with these oxidation bases by combining them with couplers or color modifiers. The variety of molecules used as oxidation bases and couplers allows a wide range of colors to be obtained.

[0010] It is thus of great interest to find new ways of synthesizing oxidation dyes and in particular couplers, which can be transposed industrially.

[0011] However, the methods for producing aromatic compounds which can notably be used in oxidation dyeing, and in particular / V-p-hydroxyethylanilines optionally substituted on the phenyl ring, are generally performed in several steps, potentially with steps of addition of reagent, and removal of unwanted reaction products (by-products), protection and deprotection, purification of intermediates, and solvent and temperature changes. Several approaches have been described in the literature for grafting the p-hydroxyethyl group onto the nitrogen atom of substituted or unsubstituted anilines.

[0012] Mention may notably be made of the grafting of a p-hydroxyethyl group by reaction with 2-chloroethyl chloroformate, 2-chloroethanol or methyl chlorooxoacetate and an aniline optionally substituted on the phenyl group, with yields of between 20% and 60% (see, for example, Journal of Heterocyclic Chemistry, K. Ajay et al. 47(6), 1275-1282, (2010), Cell Reports Medicine, D. Arpit et al., 5(5), 101552 (2024), Journal of Heterocyclic Chemistry, Shibashi, Hiroyuki; et al., 23(4), 1163-6, (1986); CN 105753832A and WO 2024 / 015793). However, the use of 2-chloroethyl chloroformate, 2-chloroethanol, methyl chlorooxoacetate and / or ethylene oxide should be avoided notably for reasons of potential toxicity problems. These “conventionaf’ methods can moreover generate waste, and are generally performed with catalysts that are rarely recyclable, under conditions of high temperature and pressure, with long reaction times (several days), which are not always practical from an industrial viewpoint and / or with yields not always optimized.

[0013] Furthermore, these compounds are interesting because they are oxidation couplers for hair dyeing. The environmentally friendly preparation of chemical compounds, that is to say preparation in which the design and development take account of environmental issues, is becoming a major preoccupation for contributing toward meeting the global challenges. It is thus essential to propose more sustainable preparation processes, thereby making it possible to respond to these environmental issues. Indeed, it is of great interest in a process for preparing chemical compounds, notably an industrial process, to think about the economy of atoms during the chemical reactions involved (for example, the majority of atoms, notably carbon atoms engaged as raw material, can be incremented in the product of the chemical reaction). It is also important during the preparation process to generate very little waste (for example, if one or more catalysts are required, to opt for a catalysis that can be recycled). Moreover, it is important that the preparation process be sparinglyenergy-intensive and that the reaction times be reduced (from a few days to a few hours and if possible less than 24 h).

[0014] Thus, there is a real need to provide a process for preparing oxidation dyes, and notably those substituted with a hydroxyethylamino group, which can meet at least one of the technical problems mentioned above.

[0015] In particular, one of the aims of the present invention is notably to propose a process for the synthesis of at least one (hetero)aromatic compound substituted with a hydroxyethylamino group which has a better carbon footprint than the processes conventionally described in the prior art and which is capable of being performed efficiently for cosmetic applications, notably for the cosmetic treatment of keratin materials, in particular human keratin fibers. One of the aims of the present invention is notably to propose a process for preparing (hetero)aromatic compounds substituted with a hydroxyethylamino group (B) from (hetero)aromatic compound(s) bearing an amino group (A) in the presence i) of one or more i-1) (alkyl)glycolaldehydes and / or one or more i-2) (di)(alkyl)glycolaldehyde dimers and also hydrated forms thereof and ii) in a preferably catalytic reduction medium according to Scheme 1, it being understood that steps i) and ii) are performed simultaneously or as a “one pot’ reaction:

[0016] [Chem. 1]

[0017]

[0018] (A) (B)

[0019] in which Scheme 1 (A) and (B):

[0020] * n has the value 1 or 2, preferably 2;

[0021] * Xi, X2, X3, X4 and X5, which may be identical or different, represent a group or atom: CR1 or N, CR2 or N, CR3 or N, CR4 or N, and CRs or N respectively with:

[0022] R1, R2, R3, R4 and Rs, which may be identical or different, represent an atom or group chosen from:

[0023] a) hydrogen,b) halogen,

[0024] c) nitro,

[0025] d) cyano,

[0026] e) hydroxyl,

[0027] f) (Ci-Ce)alkyl optionally substituted with at least one atom or group chosen from: 1) halogen, 2) hydroxyl, 3) (di)(Ci-C4)(alkyl)amino and 4) (Ci-C4)alkoxy,

[0028] g) (Ci-Ce)alkoxy in which the alkyl part of the alkoxy may optionally be substituted with one or more atoms or groups chosen from 1) to 4) as defined previously, or else

[0029] h) two contiguous groups Ri and R2, and / or R2 and R3, and / or R3 and R4, and / or R4 and Rs form, together with the carbon atoms bearing them, a saturated or unsaturated, nonaromatic or aromatic, 4- to 6-membered, preferably 5- or 6-membered, heterocycle or carbocycle, optionally substituted with one or more atoms or groups chosen from: a) to g) as defined previously, more particularly a 5-membered heterocycle preferably comprising from 1 to 3 oxygen or nitrogen atoms, preferably oxygen;

[0030] i) carboxy(late) -C(O)-O-Rs with Rs representing a hydrogen atom, a cationic counterion such as an alkali metal or an alkaline-earth metal, or a (Ci-Cs)alkyl group; preferably, Xi to X5, which may be identical or different, represent a group CR1, CR2, CR3, CR4 and CRs; more particularly, R1 to Rs represent a hydrogen atom or a group chosen from a) hydroxyl, f) (Ci-Cs)alkyl, or g) (Ci-Cs)alkoxy, or alternatively h) two contiguous groups R1 and R2, or R2 and R3, or R3 and R4, or R4 and Rs, preferably, R2 and Rsform, together with the carbon atoms bearing them, a 5-membered heterocycle preferably comprising from 1 to 3 oxygen atoms; preferably, R1 represents a hydrogen atom, R2 represents a hydrogen atom or a (Ci-C4)alkoxy group such as methoxy, R3 represents a hydrogen atom or a (Ci-C4)alkyl group, R4 represents a hydrogen atom or a hydroxyl group, and Rs represents a hydrogen atom or a (Ci-C4)alkoxy group, or alternatively R2 and R3 together form a methylenedioxy, or ethylenedioxy group, preferably a methylenedioxy group; and

[0031] * R, which may be identical or different, preferably identical, represents a hydrogen atom or a (Ci-Cs)alkyl group, preferably a hydrogen atom.

[0032] This “one pot’ step is preferably followed by a purification step, notably by recrystallization or precipitation and then filtration.

[0033] The preparation process according to the invention thus achieves the objectives as described previously, i.e. it leads to a (hetero)aromatic compound substituted with a hydroxyethylamino group (B) as defined previously with a highly satisfactory degree of purity, which is readily manipulated for cosmetic applications, notably for the treatment of keratin fibers. In addition, it appears after the simultaneous reaction of i)+ii) that the yield of compound (B) as defined previously is very satisfactory. The simultaneousimplementation of reactions i) + ii), or “one pot’ reaction, is optimized compared to conventional multi-step synthesis processes, in terms of the number of steps, in terms of the number of successive purifications and / or solvents used. The yields are very satisfactory while minimizing the number of purification steps, in particular the number of operating steps with isolation, compared with the chemical synthesis processes conventionally described in the prior art.

[0034] The synthesis process according to the invention notably makes it possible to significantly reduce the amounts of solvents, notably those derived from petrochemicals. According to a particular embodiment of the invention, the synthesis process of the invention does not involve the use of 2-chloroethyl chloroformate, 2-chloroethanol, methyl chlorooxoacetate, or ethylene oxide. According to a particular embodiment of the invention, the synthesis process of the invention does not involve the use of a halogenated solvent.

[0035] According to a particular embodiment of the invention, the process of the invention does not involve, in the reduction step ii), a borohydride as a reducing agent, and more particularly, does not involve in the reduction step ii), any hydride reducing agent.

[0036] In that which follows, and unless otherwise indicated, the limits of a range of values are included within that range, notably in the expressions “between..." and “ranging from ... to ...’’.

[0037] Moreover, the expression “at least one" used in the present description is equivalent to the expression “one or more".

[0038] In addition, the expression “at least’ used in the present description is equivalent to the expression “greater than or equal to".

[0039] As is well known, a “Cn" compound or group denotes a compound or group containing “n” carbon atoms in its chemical structure.

[0040] The term “(Cx-Cz)alkyl group" means a linear or branched hydrocarbon-based chain comprising from x to z carbon atoms, for example, a (Ci-Ce)alkyl group represents a linear or branched hydrocarbon-based chain comprising from 1 to 6 carbon atoms.

[0041] The term “(Cx-Cy)alkylene group" means a (Cx-Cz)alkyl group as defined previously, which is divalent.

[0042] The term “(Cx-Cz) alkenyl group" means a linear or branched hydrocarbon-based chain comprising from x to z carbon atoms, and comprising one or more conjugated or nonconjugated unsaturations, preferably a single unsaturation; for example, a (C2-Ce)alkenyl group represents a linear or branched hydrocarbon-based chain comprising from 2 to 6 carbon atoms and comprising one or more unsaturations.

[0043] The term “(Cx-Cy) alkenylene group" means a (Cx-Cz)alkenyl group as defined previously, which is divalent.The term “(Cx-Cz) alkoxy group" means an -O-(CX-Cz)alkyl radical, in which the (Cx-Cz)alkyl group is as defined previously; for example, mention may be made of a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a butyloxy group, a tert-butyloxy group, a pentoxy group or a hexyloxy group, preferably a methoxy group;

[0044] The term “cycloalkyl group" means a fused or non-fused, more preferentially fused, saturated or unsaturated, preferably saturated, non-aromatic, monocyclic or polycyclic carbocycle (cyclic hydrocarbon-based group), preferably of between 2 and 5 rings, comprising from 5 to 42 carbon atoms, in particular comprising from 6 to 10 carbon atoms. The term “(di)(Cx-Cz)(alkyl)amino- group" means an -N((Cx-Cz)alkyl)2 radical in which the (Cx-Cz)alkyl group is as defined previously. For example, mention may be made of a dimethylamino- group, a diethylamino- group, a (methyl)(ethyl)amino- group, a dipropylamino- group, a diisopropylamino- group or a dibutylamino- group;

[0045] The term “(hetero)aryl group” means an aryl or heteroaryl group;

[0046] The term “aryl group" means a monocyclic or fused or non-fused polycyclic carbocycle comprising from 6 to 22 carbon atoms, and in which at least one ring is aromatic; preferentially, the aryl radical is a phenyl, biphenyl, naphthyl, indenyl, anthracenyl or tetrahydronaphthyl, preferably phenyl;

[0047] The term “heteroaryl group" means a monocyclic or fused or non-fused polycyclic heterocycle, comprising from 5 to 22 carbon atoms and from 1 to 5 heteroatoms (particularly 1 to 3 heteroatoms, more particularly 1 heteroatom) such as oxygen, sulfur or nitrogen, preferably nitrogen, at least one ring of which is aromatic; in particular, the heteroaryl radical is chosen from acridinyl, benzimidazolyl, benzobistriazolyl, benzopyrazolyl, benzopyridazinyl, benzoquinolyl, benzothiazolyl, benzotriazolyl, benzoxazolyl, pyridinyl, tetrazolyl, dihydrothiazolyl, imidazopyridyl, imidazolyl, indolyl, isoquinolyl, naphthoimidazolyl, naphthoxazolyl, naphthopyrazolyl, oxadiazolyl, oxazolyl, oxazolopyridyl, phenazinyl, phenoxazolyl, pyrazinyl, pyrazolyl, pyrilyl, pyrazoyltriazyl, pyridyl, pyridinoimidazolyl, pyrrolyl, quinolyl, tetrazolyl, thiadiazolyl, thiazolyl, thiazolopyridinyl, thiazoylimidazolyl, thiopyrylyl, triazolyl, xanthyl and the ammonium salt thereof;

[0048] The term “cycloalkyl group" means a non-aromatic, monocyclic or fused or non-fused polycyclic carbocycle containing from 5 to 22 carbon atoms, which may comprise one or more unsaturations.

[0049] The term “heterocycloalkyl group" means a non-aromatic, monocyclic or fused or nonfused polycyclic 5- to 22-membered radical, including from 1 to 6 heteroatoms chosen from nitrogen, oxygen and sulfur atoms.

[0050] The term “polar organic solvent’ means a solvent which comprises carbon atoms, hydrogen atoms and one or more heteroatoms preferably chosen from oxygen, nitrogen and sulfur atoms. In particular, the polar organic solvent(s) are composed of atoms withdifferent electronegativities and the difference in electronegativity between 0.4 and 1.7, forming polarized bonds between them.

[0051] The term “protic solvent’ means solvents that are polar according to a second criterion, proticity, that is to say the ability of the solvent to release H+acid ions or to create hydrogen bonds, i.e. generally comprising hydroxyl or amino groups.

[0052] The term “aprotic polar organic solvent’ may be used to refer to di(Ci-Ce)alkyl ketones such as acetone, di(Ci-Ce)alkyl sulfoxides such as dimethyl sulfoxide (DMSO), (Ci-Ce)alkylnitriles, heterocycloalkyl and cycloalkyl(Ci-C6)alkoxy such as pyridine, THF or cyclopentyl methyl ether (CPME), or (Ci-C6)alkylcarbonyl(Ci-C6)alkoxy such as tert-butyl acetate TBA.

[0053] The term “protic polar organic solvent’ may be used to refer to (Ci-Cw)alkan(poly)ols, preferably (C2-Cs)alkanols such as methanol and ethanol or 2-methyl-2-butanol (2M2B) and more preferentially ethanol.

[0054] For the purposes of the present invention, the term “geometrical isomet’ is understood to denote any molecule of identical constitution to the formula under consideration but in which the spatial organization of the atoms is different. In particular, they may be conformational stereoisomers, i.e. compounds which differ in their rotation around a single bond, or configurational stereoisomers, in particular enantiomers or diastereoisomers. The term “anionic counterion” means an anion or an anionic group derived from an organic or mineral acid salt which counterbalances the cationic charge of the dye; more particularly, the anionic counterion is chosen from: i) halides such as chloride or bromide; ii) nitrates; iii) sulfonates, including Ci-Ce 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-O-S(O)O' such as methyl sulfate and ethyl sulfate; x) aryl sulfates: Ar-O-S(O)O' such as benzene sulfate and toluene sulfate; xi) alkoxy sulfates: Alk-O-S(O)2O' such as methoxy sulfate and ethoxy sulfate; xii) aryloxy sulfates: Ar-O-S(O)2O xiii) phosphates O=P(OH)2-Q-, O=P(O’)2-OH, O=P(O’)3, HO-[P(O)(O-)]w-P(O)(O’)2with w being an integer; xiv) acetate; xv) triflate; and xvi) borates such as tetrafluoroborate; xvii) disulfate (O=)2S(O')2 or SO42’ and monosulfate HSOT; the anionic counterion, derived from the organic or mineral acid salt, ensures the electrical neutrality of the molecule.

[0055] Moreover, the addition salts that may be used in the context of the invention are notably chosen from addition salts with a cosmetically acceptable base, such as the basifying agents as defined below, for instance alkali metal hydroxides such as sodium hydroxide, potassium hydroxide, aqueous ammonia, amines or alkanolamines.

[0056] For the purposes of the present invention, the term “organic or mineral acid or base salt’ is understood to denote a salt obtained between an ionic form of the compound under consideration and a corresponding counterion. In particular, such a salt is obtained byaddition of an organic or mineral acid or base, which is notably cosmetically acceptable, to the compound under consideration. Examples of mineral bases that may be mentioned include hydroxides or carbonates of alkali metals or alkaline-earth metals, such as sodium, potassium, calcium, ammonium, magnesium, lithium or sodium. Examples of organic bases that may be mentioned include amines or alkanolamines. Examples of acids that may be mentioned include hydrochloric acid, hydrobromic acid, sulfuric acid, alkylsulfonic acids, arylsulfonic acids, citric acid, succinic acid, tartaric acid, lactic acid, alkoxysulfinic acids, aryloxysulfinic acids, phosphoric acid and acetic acid.

[0057] For the purposes of the present invention, the term “solvate" is understood to denote the form of the compound under consideration when it is associated with a solvent. The solvates include conventional solvates formed during the process of preparing the compound under consideration. Examples of solvates are those obtained in the presence of water or of a linear or branched alcohol, in particular ethanol or isopropanol.

[0058] The term “hydrated form” of i-1) (alkyl)glycolaldehyde R-C(O)-CH2-OH or i-2) glycolaldehyde H-C(O)-CH2-OH means the hydroxylated forms thereof resulting from their reactions of the carbonyl function with water, namely i-1) R-CH(OH)2-CH2-OH or i-2) H- CH(OH)2-CH2-OH, respectively.

[0059] The term “nitro(so)" means a nitro function -NO2(also noted as -N(=O)2, -N+(=O)-O' or - N(=O)->O) or nitroso -NO (also noted as -N=O).

[0060]

[0061] The process of the invention relates to a process for preparing (hetero)aromatic compound(s) substituted with a hydroxyethylamino group (B) as described previously from (hetero)aromatic compound(s) bearing a nitro(so) group (A) as described previously in the presence i) of one or more i-1) (alkyl)glycolaldehydes and / or one or more i-2) (di)(alkyl)glycolaldehyde dimers and ii) in a preferably catalytic reduction medium, it being understood that steps i) and ii) are performed simultaneously or as a “one pot’ reaction as described previously.

[0062] According to a particular embodiment of the invention Xi, X2, X3, X4 and X5, which may be identical or different, represent a group or atom: CR1 or N, CR2or N, CR3 or N, CR4 or N, and CRs or N, respectively, provided that at least one from among Xi, X2, X3, X4 and X5 represents a nitrogen atom N; preferably, not more than one, two or three from among Xi, X2, X3, X4 and X5 represent 1, 2 or 3 nitrogen atoms, preferably 1 nitrogen atom.

[0063] According to another particular embodiment, the process is a one-step process for preparing aromatic compound(s) substituted with a hydroxyethylamino group (B1) as described below from aromatic compound(s) bearing a nitro(so) group (A1) as described below in the presence i) of one or more i-1) (alkyl)glycolaldehydes and / or one or more i-2)(di)(alkyl)glycolaldehyde dimers and ii) in a preferably catalytic reduction medium according to Scheme 2, it being understood that steps i) and ii) are performed simultaneously;

[0064] [Chem. 2]

[0065]

[0066] in which Scheme 2 n, R and Ri to Rs are as defined previously.

[0067] More particularly, the one-step process of the invention for preparing aromatic compound(s) substituted with a hydroxyethylamino group (B’1) as described below from aromatic compound(s) bearing a nitro(so) group (A’1) as described below in the presence i) of i-1) glycolaldehyde and / or of i-2) diglycolaldehyde dimer and ii) in a preferably catalytic reduction medium according to Scheme 3, it being understood that steps i) and ii) are performed simultaneously;

[0068] according to Scheme 3:[Chem. 3]

[0069]

[0070] in which Scheme 3 n and Ri to Rs are as defined previously, and R represents a hydrogen atom.

[0071] More preferentially, the process of the invention is a one-step process for preparing aromatic compound(s) substituted with a hydroxyethylamino group (B2) as described below from aromatic compound(s) bearing a nitro(so) group (A2) as described below in the presence i) of one or more i-1) (alkyl)glycolaldehydes and / or of one or more i-2) (di)(alkyl)glycolaldehyde dimers and also the hydrated forms thereof and ii) in a preferably catalytic reduction medium according to Scheme 4, it being understood that steps i) and ii) are performed simultaneously;[Chem. 4]

[0072]

[0073] in which Scheme 4 n, R, R2, 3 and Rs are as defined previously.

[0074] More particularly, the one-step process of the invention for preparing aromatic compound(s) substituted with a hydroxyethylamino group (B’2) as described below from aromatic compound(s) bearing a nitro(so) group (A’2) as described below in the presence i) of i-1) glycolaldehyde and / or of i-2) diglycolaldehyde dimer and ii) in a preferably catalytic reduction medium according to Scheme 5, it being understood that steps i) and ii) are performed simultaneously;

[0075] [Chem. 5]

[0076]

[0077] in which Scheme 5 n, R2, R3 and Rs are as defined previously, and R represents a hydrogen atom.

[0078] Preferably, the (alkyl)glycolaldehyde(s) used in i) is glycolaldehyde, i.e. R represents a hydrogen atom.

[0079] According to a particular embodiment of the invention, step i) + ii) is performed at a temperature of between 0°C and 50°C, more particularly between 10°C and 35°C, such as 25°C ± 5°C.

[0080] According to a particular embodiment of the invention, the solvent used in step i) + ii) of the process is chosen from polar aprotic organic solvents.

[0081] More particularly of ester type preferentially of formula (D): R7-C(O)-O-Rs in which: R7and Rs, which may be identical or different, represent an acyclic, linear or branched, or cyclic, saturated or unsaturated, aromatic or non-aromatic, hydrocarbon-based chain comprising from 1 to 10 carbon atoms, optionally interrupted with one or more heteroatoms such as oxygen; more preferentially, R7and Rs, which may be identical or different, represent a saturated, linear or branched acyclic hydrocarbon-based chain comprising between 1 and 8 carbon atoms; even more preferentially, R7and Rs represent a (Ci-Cs)alkyl group; more particularly, R7-C(O)-O-Rs is chosen from methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and mixtures thereof; more preferentially ethyl acetate. According to a particular embodiment of the invention, the solvent used in step i) + ii) of the process is a polar aprotic organic solvent of ketone type preferentially of formula (E): R7-C(O)-Rs in which R7and Rs are as defined previously in formula (D); more particularly, R7-C(O)-Rs is chosen from acetone, methyl ethyl ketone (MEK) and mixtures thereof.

[0082] According to a particular embodiment of the invention, the solvent used in step i) + ii) of the process is a polar aprotic organic solvent of ether type preferentially of formula (F): R’7-O-R’s in which R’7and R’s are as defined for R7and Rs above in formula (D), R’7and / or R’s may also represent a cycloalkyl group containing from 3 to 10 carbon atoms, preferably 5 carbon atoms, or else R’7and R’s, together with the oxygen atom, form a saturated or unsaturated 3- to 10-membered heterocycle, preferably a 5- to 7-membered heterocycle, optionally substituted with one or more (Ci-C4)alkyl groups such as methyl; more particularly, R’7-O-R’s is chosen from diethyl ether, (di)glyme, tetrahydrofuran (THF) and (Ci-C4)alkyl-THF such as methyl-THF, cyclopentyl methyl ether (CPME) and mixtures thereof.

[0083] According to a particular embodiment of the invention, the solvent used in step i) + ii) of the process is a polar aprotic organic solvent of amide type preferentially of formula (G): R’7R’SN-C(O)-R9 in which R’7and R’s are as defined in formula (F), preferably represent a (Ci-C4)alkyl group such as methyl, and R9 represents a hydrogen atom or a group R7asdefined above in formula (D), preferably a hydrogen atom, R’7R’sN-C(O)-R9 represent dimethylformamide (DMF).

[0084] According to another particular embodiment of the invention, the solvent used in step i) + ii) of the process is chosen from polar protic organic solvents.

[0085] According to another particular embodiment of the invention, the solvent used in step i) + ii) of the process is a polar protic organic solvent of mono- or polyhydroxylated (Ci-Cs)alkanol type preferentially of formula (H): Rg-(OH)nwith n representing an integer between 1 and 6 and Rg representing a monovalent hydrocarbon-based chain when n is 1, or a polyvalent hydrocarbon-based chain when n is from 2 to 6, comprising from 1 to 8 carbon atoms, which is acyclic, linear or branched, or cyclic, saturated or unsaturated, aromatic or non-aromatic, optionally interrupted with one or more heteroatoms such as oxygen, for instance methanol, ethanol, isopropanol, butanol, 2-butoxyethanol, propylene glycol, glycerol, 1,3-propanediol, dipropylene glycol, propylene glycol monomethyl ether, diethylene glycol monoethyl ether and monomethyl ether, and also aromatic alcohols or ethers such as benzyl alcohol or phenoxyethanol, and mixtures thereof; more preferentially, Rg represents a saturated, linear or branched, acyclic, hydrocarbon-based chain, comprising between 1 and 6 carbon atoms; even more preferentially, n is 1 and Rg represents a (C2-Ce)alkyl group; more particularly, R9-(OH)nis chosen from methanol, ethanol, isopropanol, butanol and mixtures thereof, even more preferentially ethanol.

[0086] According to another particular embodiment of the invention, the solvent used in step i) + ii) of the process is chosen from apolar aprotic organic solvents. More particularly, the apolar aprotic organic solvents are chosen from aromatic solvents such as toluene. According to another variant, the apolar organic solvents are chosen from linear or branched (poly)halogenated Ci-Ce alkanes such as dichloromethane.

[0087] According to another particular embodiment of the invention, the solvent used in step i) + ii) of the process is a mixture of polar aprotic organic solvents as defined previously.

[0088] According to another particular embodiment of the invention, the solvent used in step i) + ii) of the process is a mixture of polar protic organic solvents as defined previously.

[0089] According to another particular embodiment of the invention, the solvent used in step i) + ii) of the process is a mixture of apolar aprotic organic solvents as defined previously.

[0090] According to another variant of the invention, the solvent used in step i) + ii) of the process is a mixture of polar aprotic + apolar aprotic organic solvents as defined previously, or polar protic + polar aprotic organic solvents as defined above, or polar protic + apolar aprotic organic solvents as defined previously, or polar aprotic + polar protic + apolar aprotic organic solvents as defined previously.Particularly in the simultaneous “one pot” step, the reduction medium ii) is produced in a catalytic reduction medium more particularly in the presence of a) at least one catalytic metal chosen from nickel (Ni), palladium (Pd), ruthenium (Ru), platinum (Pt) and mixtures thereof, preferentially Pd and / or Pt, more preferentially Pd.

[0091] The catalytic metal(s) are preferably supported on a substrate (or support) which is particularly non-metallic, polymeric or non-polymeric, preferably non-polymeric, notably chosen from active carbon C or graphite, alumina such as alpha alumina, silica, silicon carbide, titanium (di)oxide or zirconium (di)oxide, or mixtures thereof, notably on charcoal (graphite), or other substrate(s) such as alumina and / or silica; and b) in the presence of hydrogen H2, more particularly at a pressure of between 1 and 15 bar, more particularly between 2 and 10 bar, such as 5 ± 0.5 bar.

[0092] According to a preferred embodiment of the invention, the catalytic metal(s) of the invention are dispersed on the substrate, notably on the active charcoal prior to hydrogenation. More particularly, the Pt and / or Pd are dispersed before reduction on the substrate, notably on the activated charcoal.

[0093] More particularly, the catalyst(s) are supported on preferentially activated carbon C or graphite and notably Pd / C.

[0094] According to a particular embodiment of the invention, the catalytic metal is present in an amount of from 0.0001 to 0.1 and from 0.1 to 1 by weight (w / w).

[0095] According to a preferred embodiment, the “one pot” step i) + ii) consists in mixing together the (hetero)aromatic compound(s) bearing a nitro(so) group (A), (A1), (A’1), (A2) and (A’2) as described previously, preferably nitro (i.e. n = 2), with one or more i-1) (alkyl)glycolaldehydes and / or one or more i-2) (di)(alkyl)glycolaldehyde dimers as defined previously with one or more supported or non-supported catalytic metals, as defined previously, in the presence of hydrogen, under the pressure as defined previously.

[0096] Preferably, the reaction of process i) and ii) is performed within a reaction time of between 30 minutes and 6 hours, more preferentially between 1 hour and 5 hours, better still between 2 hours and 4 hours.

[0097] According to a preferred embodiment of the invention, the “one pot” process i)+ii) is followed iii) by one or more purification steps such as precipitation, filtration, preparative chromatography, recrystallization, preferably by filtration notably on a sinter or a conventional filter such as cellulose.

[0098] According to a particular embodiment, the reagent(s) used in i) of the process of the invention is i-1) one or more (alkyl)glycolaldehydes and also the hydrated forms thereof, and more preferentially is glycolaldehyde, and also the hydrated form thereof.According to a preferred embodiment of the invention, the reagent used in i) of the process of the invention is i-2) one or more (di)(alkyl)glycolaldehyde dimers and also the hydrated forms thereof, more preferentially glycolaldehyde dimer, namely 2,5-dihydroxy-1,4-dioxane, and also the hydrated forms thereof.

[0099] According to a more preferred embodiment of the invention, the reagent used in i) of the process of the invention is a mixture of i-1) + i-2) as defined previously, more particularly the mixture of glycolaldehyde dimer and glycolaldehyde monomer and also the hydrated forms thereof.

[0100] Preferably, the reagent (A) is nitro(so)benzene, i.e. in which Xi, X2, X3, X4 and X5, which may be identical or different, represent a group: CR1, CR2, CR3, CR4 or CRs, or a nitro(so)benzene chosen from (A1), (A’1), (A2) and (A’2) in which:

[0101] * R1 , R2, R3, R4 and Rs represent a hydrogen atom, or

[0102] * R1, R4 and Rs represent a hydrogen atom, R2 represents a hydroxyl group and R3 represents a (Ci-C4)alkyl group such as methyl; or

[0103] * R1, R3 and R4 represent a hydrogen atom, and R2 and Rs, which may be identical or different, represent a (Ci-C4)alkoxy group such as methoxy; or

[0104] * R1, R4 and Rs represent a hydrogen atom and R2 and R3 form, together with the carbon atoms bearing them, a fused monocyclic 5- or 6-membered heterocycle comprising one or more heteroatoms chosen from O and N, preferably one or two oxygen atom(s); preferably, R2 and R3 together form a methylenedioxy or ethylenedioxy group, more preferentially methylenedioxy.

[0105] More preferentially, the reagent bearing a nitro(so) group (A), (A’1 ), (A1), (A2) or (A’2) is chosen from:

[0106] [Table 1]

[0107]

[0108] to produce, according to the process of the invention, the preferred reaction products (B), (B1), (B’1), (B2) or (B’2) chosen from the following:[Table 2]

[0109]

[0110] The examples that follow serve to illustrate the invention without, however, being limiting in nature.

[0111]

[0112] Example 1 Synthesis of compound B-(1) / \ / -2-hydroxyethylaniline:

[0113] [Chem. 6]

[0114]

[0115] Nitrobenzene A-(1) (3.08 g, 25 mmol, 1 eq.), glycolaldehyde dimer [reference G6805 from Sigma-Aldrich] (1.56 g, 13 mmol, 0.52 eq.), wet Pd / C (1 mol%, 1.06 g) and ethyl acetate (10 mL) were introduced into a 250 mL stainless steel autoclave.

[0116] The mixture was purged three times with hydrogen (3 * 1 bar).

[0117] The hydrogenator was then filled with hydrogen.

[0118] The mixture was stirred at 25°C for 2 hours under a pressure of 5 bar.

[0119] The reaction mixture was then concentrated under vacuum.

[0120] The residue obtained was purified by flash chromatography (with a heptane / ethyl acetate mixture as eluent) to give the desired N-2-hydroxyethylaniline B-(1) (2.0 g, 58%, purity > 98 %) in the form of a yellowish oil.

[0121] Example 2: Synthesis of compound B-(2) / \ / -2-hydroxyethyl-3-hydroxy-4-methylaniline:

[0122] [Chem. 7]

[0123]

[0124] Compound B-(2) can be obtained by repeating the protocol of Example 1, replacing the same molar amount of nitrobenzene A-(1) with 3-hydroxy-4-methylnitrobenzene A-(2).Example 3: Synthesis of compound B-(3) / \ / -2-hydroxyethyl-3,6-dimethoxyaniline:

[0125] [Chem. 8]

[0126]

[0127] The experimental protocol is identical to that of Example 1, starting with 1 ,4-dimethoxy-2-nitrobenzene A-(3) (15.6 mmol).

[0128] After purification, the desired N-2-hydroxyethyl-3,6-dimethoxyaniline B-(3) is obtained (50%, purity > 98 %) in the form of a yellowish solid.

[0129] Example 4: Synthesis of compound B-(4) / \ / -2-hydroxyethyl-3,4-methylenedioxyaniline: [Chem. 9]

[0130]

[0131] Compound B-(4) is obtained (purity > 98 %) by repeating the protocol of Example 1, replacing the same molar amount of nitrobenzene A-(1) with 3,4-methylenedioxynitrobenzene A-(4).

[0132] Purity is determined via NMR (Nuclear Magnetic Resonance) spectroscopy or HPLC (High-Performance Liquid Chromatography) analysis.

Claims

1. CLAIMS1. A process for preparing (hetero)aromatic compounds substituted with a hydroxyethylamino group (B) from (hetero)aromatic compound(s) bearing a nitro(so) group (A) in the presence i) of one or more i-1) (alkyl)glycolaldehydes and / or one or more i-2) (di)(alkyl)glycolaldehyde dimers and also hydrated forms thereof and ii) in a preferably catalytic reduction medium according to Scheme 1, it being understood that steps i) and ii) are performed simultaneously or as a “one pot’ reaction:Scheme 1(A) (B)in which Scheme 1 (A) and (B):* n has the value 1 or 2, preferably 2;* Xi, X2, X3, X4 and X5, which may be identical or different, represent a group or atom: CR1 or N, CR2 or N, CR3 or N, CR4 or N, and CRs or N respectively with:R1, R2, R3, R4 and Rs, which may be identical or different, represent an atom or group chosen from:a) hydrogen,b) halogen,c) nitro,d) cyano,e) hydroxyl,f) (Ci-Cs)alkyl optionally substituted with at least one atom or group chosen from: 1) halogen, 2) hydroxyl, 3) (di)(Ci-C4)(alkyl)amino and 4) (Ci-C4)alkoxy,g) (Ci-Cs)alkoxy in which the alkyl part of the alkoxy may optionally be substituted with one or more atoms or groups chosen from 1) to 4) as defined previously, or elseh) two contiguous groups Ri and R2, and / or R2 and R3, and / or R3 and R4, and / or R4 and Rs form, together with the carbon atoms bearing them, a saturated or unsaturated, nonaromatic or aromatic, 4- to 6-membered heterocycle or carbocycle, optionally substituted with one or more atoms or groups chosen from: a) to g) as defined previously;i) carboxy(late) -C(O)-O-Rs with Rs representing a hydrogen atom, a cationic counterion such as an alkali metal or an alkaline-earth metal, or a (Ci-Cs)alkyl group; and* R, which may be identical or different, preferably identical, represents a hydrogen atom or a (Ci-Cs)alkyl group, preferably a hydrogen atom.

2. The process as claimed in the preceding claim, wherein Xi, X2, X3, X4 and X5, which may be identical or different, represent a group or atom: CR1 or N, CR2 or N, CR3 or N, CR4 or N, and CRs or N, respectively, provided that at least one from among Xi, X2, X3, X4 and X5 represents a nitrogen atom N; preferably, not more than one, two or three from among Xi, X2, X3, X4 and X5 represent 1, 2 or 3 nitrogen atoms, preferably 1 nitrogen atom.

3. The process as claimed in claim 1, for preparing aromatic compound(s) substituted with a hydroxyethylamino group (B1) as described below from aromatic compound(s) bearing a nitro(so) group (A1) as described below in the presence i) of one or more i-1) (alkyl)glycolaldehydes and / or one or more i-2) (di)(alkyl)glycolaldehyde dimers and ii) in a preferably catalytic reduction medium according to Scheme 2, it being understood that steps i) and ii) are performed simultaneously;Scheme 2in which Scheme 2 n, R and Ri to Rs are as defined in claim 1; more particularly, Ri to Rs represent a hydrogen atom or a group chosen from e) hydroxyl, f) (Ci-Cs)alkyl, or g) (Ci-Cs)alkoxy, or alternatively h) two contiguous groups Ri and R2, or R2 and R3, or R3 and R4, or R4and Rs, preferably, R2 and Rsform, together with the carbon atoms bearing them, a 5-membered heterocycle preferably comprising from 1 to 3 oxygen atoms; preferably, Ri represents a hydrogen atom, R2 represents a hydrogen atom or a (Ci-C4)alkoxy group such as methoxy, R3 represents a hydrogen atom or a (Ci-C4)alkyl group, R4represents a hydrogen atom or a hydroxyl group, and Rs represents a hydrogen atom or a (Ci-C4)alkoxy group, or alternatively R2and R3 together form a methylenedioxy, or ethylenedioxy group, preferably a methylenedioxy group.

4. The process as claimed in claim 1 or 3, for preparing aromatic compound(s) substituted with a hydroxyethylamino group (B’1) as described below from aromatic compound(s) bearing a nitro(so) group (A’1) as described below in the presence i) of i-1) glycolaldehyde and / or i-2) diglycolaldehyde dimer and ii) in a preferably catalytic reduction medium according to Scheme 3, it being understood that steps i) and ii) are performed simultaneously; according to Scheme 3:Scheme 3in which Scheme 3 n and Ri to Rs are as defined in the preceding claim, and R represents a hydrogen atom;preferentially, the process is a one-step process for preparing aromatic compound(s) substituted with a hydroxyethylamino group (B2) as described below from aromaticcompound(s) bearing a nitro(so) group (A2) as described below in the presence i) of one or more i-1) (alkyl)glycolaldehydes and / or one or more i-2) (di)(alkyl)glycolaldehyde dimers and also the hydrated forms thereof and ii) in a preferably catalytic reduction medium according to Scheme 4, it being understood that steps i) and ii) are performed simultaneously;Scheme 4in which Scheme 4 n, R, R2, 3 and Rs are as defined previously;more particularly, the one-step process of the invention for preparing aromatic compound(s) substituted with a hydroxyethylamino group (B’2) as described below from aromatic compound(s) bearing a nitro(so) group (A’2) as described below in the presence i) of i-1) glycolaldehyde and / or of i-2) diglycolaldehyde dimer and ii) in a preferably catalytic reduction medium according to Scheme 5, it being understood that steps i) and ii) are performed simultaneously;Scheme 5in which Scheme 5 n, R2, R3 and Rs are as defined previously, and R represents a hydrogen atom.

5. The process as claimed in any one of the preceding claims, wherein the (alkyl)glycolaldehyde(s) used in i) is glycolaldehyde, i.e. R represents a hydrogen atom.

6. The process as claimed in any one of the preceding claims, wherein step i) + ii) is performed at a temperature of between 0°C and 50°C, more particularly between 10°C and 35°C, such as 25°C ± 5°C.

7. The process as claimed in any one of the preceding claims, wherein the solvent used in step i) + ii) of the process is chosen from polar aprotic organic solvents;particularly of ester type, preferentially of formula (D): R?-C(O)-O-R8 in which: R? and Rs, which may be identical or different, represent an acyclic, linear or branched, or cyclic, saturated or unsaturated, aromatic or non-aromatic, hydrocarbon-based chain comprising from 1 to 10 carbon atoms, optionally interrupted with one or more heteroatoms such as oxygen; more preferentially, R? and Rs, which may be identical or different, represent a saturated, linear or branched acyclic hydrocarbon-based chain comprising between 1 and 8 carbon atoms; even more preferentially, R? and Rs represent a (Ci-Cs)alkyl group; more particularly, R7-C(O)-O-Rs is chosen from methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and mixtures thereof, preferably ethyl acetate;particularly of ketone type, preferentially of formula (E): R7-C(O)-Rs in which R? and Rs are as defined previously in formula (D); more particularly, R7-C(O)-Rs is chosen from acetone, methyl ethyl ketone (MEK) and mixtures thereof;particularly of ether type, preferentially of formula (F): R’7-O-R’s in which R’7and R’s are as defined for R? and Rs above in formula (D), R’7and / or R’s may also represent a cycloalkyl group containing from 3 to 10 carbon atoms, preferably 5 carbon atoms, or else R’7and R’s, together with the oxygen atom, form a saturated or unsaturated 3- to 10-membered heterocycle, preferably a 5- to 7-membered heterocycle, optionally substituted with one or more (Ci-C4)alkyl groups such as methyl; more particularly, R’yO-R’s is chosen from diethyl ether, (di)glyme, tetrahydrofuran (THF) and (Ci-C4)alkyl-THF such as methyl-THF, cyclopentyl methyl ether (CPME) and mixtures thereof; orparticularly of amide type, preferentially of formula (G): R’7R’sN-C(O)-R9 in which R’7and R’s are as defined in formula (F), preferably represent a (Ci-C4)alkyl group such as methyl, and Rg represents a hydrogen atom or a group R7 as defined above in formula (D), preferably a hydrogen atom, R’7R’sN-C(O)-R9 represent dimethylformamide (DMF).

8. The process as claimed in any one of claims 1 to 6, wherein the solvent used in step i) + ii) of the process is chosen from polar protic organic solvents; particularly of mono- or polyhydroxylated (Ci-Cs)alkanol type, preferentially of formula (H): Rg-(OH)nwith n representing an integer between 1 and 6 and Rg representing a monovalent hydrocarbonbased chain when n is 1, or a polyvalent hydrocarbon- based chain when n is from 2 to 6, comprising from 1 to 8 carbon atoms, which is acyclic, linear or branched, or cyclic, saturated or unsaturated, aromatic or non-aromatic, optionally interrupted with one or more heteroatoms such as oxygen, for instance methanol, ethanol, isopropanol, butanol, 2-butoxyethanol, propylene glycol, glycerol, 1,3-propanediol, dipropylene glycol, propylene glycol monomethyl ether, diethylene glycol monoethyl ether and monomethyl ether, and also aromatic alcohols or ethers such as benzyl alcohol or phenoxyethanol, and mixtures thereof; more preferentially, R9represents a saturated, linear or branched, acyclic, hydrocarbon-based chain, comprising between 1 and 6 carbon atoms; even more preferentially, n is 1 and Rg represents a (C2-Cs)alkyl group; more particularly, Rg-(OH)nis chosen from methanol, ethanol, isopropanol, butanol and mixtures thereof, more preferentially ethanol.

9. The process as claimed in any one of claims 1 to 6, wherein the solvent used in step i) + ii) of the process is chosen from apolar aprotic organic solvents; particularly chosen from aromatic solvents such as toluene or linear or branched (poly)halogenated Ci-Cs alkane solvents such as dichloromethane.

10. The process as claimed in any one of the preceding claims, wherein the solvent used in step i) + ii) of the process is:- either a mixture of polar aprotic organic solvents as defined in claim 7;- or a mixture of polar protic organic solvents as defined in claim 8;- or a mixture of apolar aprotic organic solvents as defined in claim 9;- or a mixture of polar aprotic organic solvent(s) + apolar aprotic organic solvent(s) as defined previously;- or a mixture of polar protic organic solvent(s) + polar aprotic organic solvent(s) as defined previously;- or a mixture of polar protic organic solvent(s) + apolar aprotic organic solvent(s) as defined previously;- or a mixture of polar aprotic organic solvent(s) + polar protic organic solvent(s) + apolar aprotic organic solvent(s) as defined previously.

11. The process as claimed in any one of the preceding claims, wherein, in the simultaneous step i) + ii) of the process, does not involve, in the reduction step ii), a borohydride as a reducing agent, and more particularly, does not involve in the reduction step ii), any hydride reducing agent.

12. The process as claimed in any one of the preceding claims, wherein, in the simultaneous step i) + ii) of the process, the reduction reaction ii) is performed in a catalytic reduction medium in the presence of:a) at least one catalytic metal chosen from nickel (Ni), palladium (Pd), ruthenium (Ru), platinum (Pt) and mixtures thereof, preferentially Pd and / or Pt, more preferentially Pd; the catalytic metal(s) preferably being supported on a substrate, particularly a polymeric or non-polymeric, preferably non-polymeric, non-metallic substrate, notably chosen from activated charcoal C or graphite, alumina such as alpha alumina, silica, silicon carbide, titanium (di)oxide or zirconium (di)oxide, or mixtures thereof, notably on charcoal (graphite), or other substrate(s) such as alumina and / or silica; andb) hydrogen H2, more particularly at a pressure of between 1 and 15 bar, more particularly between 2 and 10 bar, such as 5 ± 0.5 bar;more particularly, the catalytic metal(s) are supported on preferentially activated charcoal C or graphite and notably Pd / C.

13. The process as claimed in any one of the preceding claims, wherein the simultaneous step i) + ii) of the process is performed within a reaction time of between 30 minutes and 6 hours, more preferentially between 1 hour and 5 hours, better still between 2 hours and 4 hours.

14. The process as claimed in any one of the preceding claims, which is followed iii) by one or more purification steps such as precipitation, filtration, preparative chromatography, recrystallization, preferably by filtration notably on a sinter or a conventional filter such as cellulose.

15. The process as claimed in any one of the preceding claims, wherein the reagent(s) used in i) are:- either i-1) one or more (alkyl)glycolaldehydes, more preferentially glycolaldehyde;- or i-2) one or more (di)(alkyl)glycolaldehyde dimers and also hydrated forms thereof, more preferentially glycolaldehyde dimer, namely 2,5-dihydroxy-1,4-dioxane, and also the hydrated forms thereof;- or a mixture of i-1) + i-2) as defined previously, more particularly the mixture of glycolaldehyde dimer and glycolaldehyde monomer, and also the hydrated forms thereof.

16. The process as claimed in any one of the preceding claims, wherein step i) + ii) consists in mixing together the (hetero)aromatic compound(s) bearing a nitro(so) group (A), (A1), (A'1), (A2) and (A'2) as described in any one of claims 1 to 4, preferably with a nitro group, with one or more i-1) (alkyl)glycolaldehydes and / or one or more i-2) (di)(alkyl)glycolaldehyde dimers as defined in any one of claims 1 to 4 and 15, with one or more supported or non-supported catalytic metals, as defined previously, in the presence of hydrogen, under the pressure as defined in claim 12.

17. The process as claimed in any one of the preceding claims, wherein the reagent (A) is a nitro(so)benzene in which Xi, X2, X3, X4 and X5, which may be identical or different, represent a group: CR1, CR2, CR3, CR4 or CRs, or a nitro(so)benzene chosen from (A1), (A’1), (A2) and (A’2) in which:* R1 , R2, R3, R4 and Rs represent a hydrogen atom, or* Ri, R4 and R5 represent a hydrogen atom, R2 represents a hydroxyl group and R3 represents a (Ci-C4)alkyl group such as methyl; or* R1, R3 and R4 represent a hydrogen atom, and R2 and Rs, which may be identical or different, represent a (Ci-C4)alkoxy group such as methoxy; or* R1, R4 and Rs represent a hydrogen atom and R2 and R3 form, together with the carbon atoms bearing them, a fused monocyclic 5- or 6-membered heterocycle comprising one or more heteroatoms chosen from O and N, preferably one or two oxygen atom(s); preferably, R2 and R3 together form a methylenedioxy or ethylenedioxy group, more preferentially methylenedioxy.

18. The process as claimed in any one of the preceding claims, wherein the reagent (A), (A1), (A’1), (A2) or (A’2) is a nitro(so)benzene chosen from:to produce, according to the process of any one of the preceding claims, the reaction products (B), (B1), (B’1), (B2) or (B’2) chosen from the following:< "

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