Process for the preparation of a (hetero)aromatic oxidation dye having a hydroxyalkylamino group for keratin fibres starting from an alkylene carbonate and a (hetero)aromatic compound having an amino group

Abstract

The invention relates to a process for the preparation of one or more (hetero)aromatic compound(s) substituted by a hydroxyalkylamino group (B) starting from one or more aromatic compound(s) having an amino group (A) in the presence i) of one or more optionally substituted (C2-C6)alkylene carbonates and ii) of one or more ionic liquid(s), then iii) in alkaline medium, optionally followed iv) by one or more purification stage(s), it being understood that the process is carried out "one pot", i.e. without isolating the intermediate (hetero)aromatic compound(s) substituted by a cyclic carbamate group.

Description

Process for the preparation of a (hetero)aromatic oxidation dye having a hydroxyalkylamino group for keratin fibres starting from an alkylene carbonate and a (hetero)aromatic compound having an amino group

[0001] The invention relates to a process for the preparation of one or more (hetero)aromatic compound(s) substituted by a hydroxyalkylamino group(B)starting from one or more aromatic compound(s) having an amino group(A)in the presence i) of one or more optionally substituted (C2-C6)alkylene carbonates and ii) of one or more ionic liquid(s), then iii) in alkaline medium, optionally followed iv) by one or more purification stage(s), it being understood that the process is carried out in "one pot” fashion, i.e. without isolating the intermediate (hetero)aromatic compound(s) substituted by a cyclic carbamate group.

[0002] For a long time, many people have sought to modify the colour of their hair and in particular to mask their grey hair.

[0003] In the field of the dyeing of hair keratin fibres, in particular human hair keratin fibres, it is already known to dye hair keratin fibres by various techniques starting from direct dyes or from pigments for non-permanent colourings or from dye precursors for permanent colourings.

[0004] There are essentially three types of processes for dyeing the hair:

[0005] a) “permanent” dyeing, the function of which is to provide a substantial modification to the natural colour and which employs oxidation dyes which penetrate into the hair fibre and form the dye via an oxidative condensation process;

[0006] b) non-permanent, semi-permanent or direct dyeing, which does not employ the oxidative condensation process and withstands 4 or 5 shampooing operations; it consists in dyeing keratin fibres with dyeing compositions containing direct dyes;

[0007] c) temporary dyeing, which gives rise to a modification of the natural colour of the head of hair which lasts from one shampooing operation to the next and which serves to enhance or correct a shade which has already been obtained. It can also be likened to a “make-up” process.

[0008] It is thus known to dye keratin fibres, in particular human keratin fibres, such as the hair, in order to obtain “permanent” colourings with dyeing compositions containing oxidation dye precursors, in particular 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 colourless or weakly coloured compounds which, when combined with oxidizing products, can give rise to coloured compounds by an oxidative condensation process.

[0009] It is also possible to vary the shades obtained with these oxidation bases by combining them with couplers or colour modifiers. The variety of the molecules brought into play as oxidation bases and couplers makes it possible to obtain a rich palette of colours.

[0010] It is thus of great interest to find novel routes for the synthesis of oxidation dyes and in particular of couplers which can be applied industrially.

[0011] In point of fact, methods for the production of aromatic compounds which in particular can be used in oxidation dyeing and especiallyN-β-hydroxyalkylanilines optionally substituted on the phenyl ring and more particularlyN-β-hydroxyethylanilines are generally carried out in several stages, with potentially stages of addition of reactant and of removal of undesired reaction products (by-products), of protection and deprotection, of purifications of intermediates, of change of solvents and of temperature. Several approaches have been described in the scientific literature or in patent applications for grafting the β-hydroxyalkyl group to the nitrogen atom of substituted or unsubstituted anilines. Mention may in particular be made of the grafting of the β-hydroxyethyl group by reaction with 2-chloroethyl chloroformate, 2-chloroethanol or methyl methylchlorooxoacetate and an aniline optionally substituted on the phenyl group, with yields of between 20% and 60% (see, for example,Journal of Heterocyclic Chemistry, K. Ajayet al., 47(6), 1275-1282, (2010);Cell Reports Medicine, D. Arpitet al., 5(5), 101552 (2024);Journal of Heterocyclic Chemistry, Shibashi, Hiroyukiet al., 23(4), 1163-6, (1986); CN 105753832A and WO 2024 / 015793). Nevertheless, the use of 2-chloroethyl chloroformate, 2-chloroethanol, methyl methylchlorooxoacetate and / or ethylene oxide is to be avoided for reasons in particular of potential toxicity problems.

[0012] These “conventional” methods touched on above can in addition generate waste and are generally carried out by rarely recyclable catalysis, which are not always practical from the industrial viewpoint, and / or with yields which are not sufficiently optimized.

[0013] Furthermore, these oxidation dyes are advantageous because they are hair dyeing oxidation couplers.

[0014] The preparation of environmentally friendly chemical compounds, that is to say compounds whose design and development take account of environmental issues and of toxicity, is becoming a major preoccupation for contributing towards meeting global challenges.

[0015] It is thus proving to be essential to provide more sustainable preparation processes thus making it possible to respond to these environmental issues. Specifically, it is of great advantage, in a process for the preparation of chemical compounds, in particular an industrial process, to think about using solvents which are, if possible, renewable, inexpensive and sparingly toxic, indeed even non-toxic, to human beings and / or the environment, in particular using, as solvent, a polar protic solvent, such as water. In addition, if one or more catalysts are required, to opt for a catalysis which is, as much as possible, eco-efficient. Moreover, it is important for the preparation process to have a synthesis yield, if possible, of greater than 80%, to be not very energy-consuming and to reduce the reaction times (from a few days to a few hours and, if possible, less than 24 h). Finally, it is essential for operators to be exposed as little as possible to products known as being possibly toxic.

[0016] Thus, there exists a real need to make available a process for the preparation of oxidation dyes and in particular those substituted by a hydroxyalkylamino group which can respond to at least one of the abovementioned technical problems.

[0017] In particular, one of the aims of the present invention is especially to provide a process for the synthesis of at least one aminated (hetero)aromatic compound substituted by a hydroxyalkylamino, preferably hydroxyethylamino, group having a better carbon footprint than the processes conventionally described in the state of the art and which can be effectively employed for cosmetic applications, in particular for the cosmetic treatment of keratin substances, especially human keratin fibres.

[0018] Moreover, studies have been carried out into a direct way of chemically accessing cyclic carbamate (hetero)aromatic compounds (3-aryloxazolidin-2-ones, 3,3'-aryldioxazolidin-2-ones and 3-aryl[1,3]oxazinan-2-ones) from cyclic carbonates and from (hetero)aromatic amines in the presence in particular of a basic ionic liquid: 1-butyl-3-methylimidazolium acetate (BmimOAc) (Chem. Cat. Chem., L. Zhanget al., 3, 1359-1364, 2011 - DOI: 10.1002 / cctc.201100016,Adv. Synth. Catal., B.Wanget al., Vol. 356,14-15, pp 3125-3134, October 13, 2014 - DOI: 10.1002 / adsc.201400026). Nevertheless, it appears from these scientific papers that the cyclic carbamates were isolated and purified (by silica gel chromatography) without providing subsequent synthesis stages. They focus only on the methodology and the mechanistic study of generation of said carbamates.

[0019] Furthermore, the N-alkylation of aromatic amines (such as aniline) with alkylene carbonates (such as ethylene carbonate) in the presence of various catalysts, including metal oxides, hydrotalcites, and different zeolites, has been described (see Shivarkar, A. B., et al. Synlett, Georg Thieme Verlag, DE, 9(1), 1374-1378 (2006), DOI: 10.1055 / s-2006-939697. ISSN: 0936-5214). The reaction of primary aromatic amines with alkylene carbonates (ethylene carbonate – EC and propylene carbonate – PC) for the selective synthesis of bis-N-(2-hydroxy)alkylamines, in the presence of phosphonium-type ionic liquids (PILs), has also been disclosed (see Selva, M., et al. Organic & Biomolecular Chemistry, 8(22), 5187-5198 (2010), DOI: 10.1039 / c0ob00105h. ISSN: 1477-0520). None of these processes describe reaction conditions combining a cyclic carbonate, an alkaline base, and an ionic liquid.

[0020] Thus, the technical problems touched on above have been solved by providing a process for the preparation of one or more (hetero)aromatic compound(s) substituted by a hydroxyalkylamino group(B), and also its organic or inorganic acid or base salts, and its solvates, such as hydrates, employing, during a first stage, the mixing of one or more (hetero)aromatic compound(s) having an amino group(A)with i) one or more optionally substituted alkylene carbonate(s) and ii) one or more ionic liquid(s) preferably chosen from imidazolium, triazolium and pyridinium salt(s), and then, during a second stage iii), the addition of one or more alkaline base(s), according to Scheme 1, it being understood that the process is carried out in "one pot” fashion, i.e. without isolating the intermediate (hetero)aromatic compound(s) substituted by a cyclic carbamate group(AB):

[0021] [Chem. 1]

[0022] Scheme 1, in which(A),(B)and(AB):

[0023] * nrepresents the molar equivalent number, preferably is of between 1 and 10, preferentially between 2 and 8 and more particularly between 3 and 6, such as 5;

[0024] * pis an integer of between 1 and 5; in particular, p has the value 1 or 2, preferentially p has the value 1;

[0025] * X1,X2,X3,X4andX5, which are identical or different, represent a group or atom: CR1or N, CR2or N, CR3or N, CR4or N, and CR5or N respectively with:

[0026] - R1, R2, R3, R4and R5, which are identical or different, represent an atom or group chosen from:

[0027] a) hydrogen,

[0028] b) halogen,

[0029] c) nitro(so),

[0030] d) cyano,

[0031] e) hydroxy,

[0032] f) (C1-C6)alkyl optionally substituted by at least one atom or group chosen from: 1) halogen, 2) hydroxy, 3) (di)(C1-C4)(alkyl)amino and 4) (C1-C4)alkoxy,

[0033] g) (C1-C6)alkoxy, the alkyl part of the alkoxy of which can optionally be substituted by one or more atom(s) or group(s) chosen from i) to iv) as defined above,

[0034] h) amino RaRbN- with Raand Rb, which are identical or different, representing a hydrogen atom or a (C1-C6)alkyl group, or else two groups Raand Rbform, together with the nitrogen atom which carries them, a saturated or unsaturated, 4- to 6-membered, preferably 5- or 6-membered, heterocycle, such as morpholino, piperazino or piperidino, optionally substituted by one or more (C1-C4)alkyl group(s), such as methyl;

[0035] i) two contiguous groups R1and R2, and / or R2and R3, and / or R3and R4, and / or R4and R5form, together with the carbon atoms which carry them, a saturated or unsaturated, non-aromatic or aromatic, 4- to 6-membered, preferably 5- or 6-membered, heterocycle or carbocycle optionally substituted by one or more atom(s) or group(s) chosen from: a) to g) as defined above, more particularly a 5-membered heterocycle preferably comprising from 1 to 3 oxygen or nitrogen, preferably oxygen, atoms;

[0036] j) carboxy(late) -C(O)-ORwith Rrepresenting a hydrogen atom, a cationic counterion, such as alkali metal or alkaline earth metal, or a (C1-C6)alkyl group;

[0037] preferably,X1toX5, which are identical or different, represent a CR1, CR2, CR3, CR4and CR5group; more particularly, R1to R5represent a hydrogen atom or a group chosen from a) hydroxy, f) (C1-C6)alkyl, or g) (C1-C6)alkoxy, or else k) two contiguous groups R1and R2, or R2and R3, or R3and R4, or R4and R5, preferably R2and R3,form, together with the carbon atoms which carry them, a 5-membered heterocycle preferably comprising from 1 to 3 oxygen atoms; preferably, R1represents a hydrogen atom, R2represents a hydrogen atom or a (C1-C4)alkoxy group, such as methoxy, R3represents a hydrogen atom or a (C1-C4)alkyl group, R4represents a hydrogen atom or a hydroxyl group and R5represents a hydrogen atom or a (C1-C4)alkoxy group, or else R2and R3together form a methylenedioxy or ethylenedioxy, preferably methylenedioxy, group; and

[0038] * R6andR7, which are identical or different, represent a hydrogen atom or group chosen from (C1-C6)alkyl, such as methyl, (C1-C6)alkoxy, aryloxy, such as phenoxy, or aryloxy(C1-C6)alkyl, particularly phenoxy(C1-C4)alkyl, such as phenoxymethyl, preferably,R6andR7represent a hydrogen atom or a (C1-C4)alkyl group, such as methyl.

[0039] This “one pot” stage is preferably followed iv) by one or more stage(s) of purification, in particular by recrystallization or precipitation, then filtration.

[0040] The preparation process according to the invention thus makes it possible to achieve the objectives as described above, that is to say that it results in a (hetero)aromatic compound substituted by a hydroxyalkylamino group(B)as defined above with a very satisfactory degree of purity, which can be easily handled for cosmetic applications, in particular for the treatment of keratin fibres. In addition, it appears, after the reaction of i)+ii)+iii), that the yield of the compound(B)as defined above is very satisfactory. The implementation of the reaction i) + ii) + iii) in “one pot” fashion, without isolating the intermediate(AB), is optimized compared with the conventional synthesis processes in terms of number of stages, in terms of the number of successive purifications and / or of solvents used. The yields are very satisfactory while minimizing the number of purification stages, in particular the number of stages of operation with isolation, compared with the processes of synthesis by the chemical route conventionally described in the state of the art.

[0041] Furthermore, the process of the invention is more virtuous, in particular from the industrial viewpoint, since it does not employ reactants known as possibly being potentially toxic, such as 2-chloroethyl chloroformate, 2-chloroethanol or methyl methylchlorooxoacetate, and / or ethylene oxide.

[0042] The synthesis process according to the invention additionally makes it possible to significantly reduce the amounts of solvents, in particular those resulting from petrochemistry. This is because, preferentially, the chemical reaction of the process of the invention takes place without a petrochemical solvent since the optionally substituted (C2-C6)alkylene carbonate(s) and in particular ethylene carbonate is a reactant which also acts as solvent.

[0043] In that which follows and unless otherwise indicated, the limits of a range of values are included in this range, in particular in the expressions “of between” and “ranging from ... to ...”.

[0044] Moreover, the expression “at least one” used in the present description is equivalent to the expression “one or more”.

[0045] In addition, the expression "at least" used in the present description is equivalent to the expression "greater than or equal to".

[0046] In a way known per se, a "Cn" compound or group denotes a compound or a group containing, in its chemical structure, "n" carbon atoms.

[0047] The term “(Cx-Cz)alkyl” group is understood to mean a linear or branched hydrocarbon chain comprising from x to z carbon atoms; for example, a (C1-C6)alkyl group represents a linear or branched hydrocarbon chain comprising from 1 to 6 carbon atoms.

[0048] The term “(Cx-Cy)alkylene” group is understood to mean a (Cx-Cz)alkyl group as defined above which is divalent.

[0049] The term "(Cx-Cz)alkenyl" group is understood to mean a linear or branched hydrocarbon chain comprising from x to z carbon atoms and comprising one or more conjugated or non-conjugated unsaturations, preferably a single unsaturation; for example, a (C2-C6)alkenyl group represents a linear or branched hydrocarbon chain comprising from 2 to 6 carbon atoms and comprising one or more unsaturations.

[0050] The term “(Cx-Cz)alkenylene” group is understood to mean a (Cx-Cz)alkenyl group as defined above which is divalent.

[0051] The term "(Cx-Cz)alkoxy" group is understood to mean an -O-(Cx-Cz)alkyl radical, in which the (Cx-Cz)alkyl group is as defined above; 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.

[0052] The term “cycloalkyl” group is understood to mean a fused or non-fused, more preferentially fused, saturated or unsaturated, preferably saturated, non-aromatic, monocyclic or polycyclic carbocycle (cyclic hydrocarbon group), preferably of between 2 and 5 rings, comprising from 5 to 42 carbon atoms, in particular comprising from 6 to 10 carbon atoms.

[0053] The term “di(Cx-Cz)(alkyl)amino” group is understood to mean an -N((Cx-Cz)alkyl)2radical in which the (Cx-Cz)alkyl group is as defined above. 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.

[0054] The term "(hetero)aryl" group is understood to mean an aryl or heteroaryl.

[0055] The term “aryl” group is understood to mean a monocyclic or fused or non-fused polycyclic carbocycle comprising from 6 to 22 carbon atoms, at least one ring of which is aromatic; preferentially, the aryl radical is a phenyl, biphenyl, naphthyl, indenyl, anthracenyl or tetrahydronaphthyl, preferably phenyl.

[0056] The term “heteroaryl” group is understood to mean a monocyclic or fused or non-fused polycyclic heterocycle, comprising from 5 to 22 carbon atoms and from 1 to 5 heteroatoms (particularly from 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, imidazopyridinyl, imidazolyl, indolyl, isoquinolyl, naphthoimidazolyl, naphthooxazolyl, naphthopyrazolyl, oxadiazolyl, oxazolyl, oxazolopyridyl, phenazinyl, phenooxazolyl, pyrazinyl, pyrazolyl, pyrilyl, pyrazoyltriazyl, pyridyl, pyridinoimidazolyl, pyrrolyl, quinolyl, tetrazolyl, thiadiazolyl, thiazolyl, thiazolopyridinyl, thiazoylimidazolyl, thiopyrylyl, triazolyl, xanthyl and its ammonium salt.

[0057] The term "cycloalkyl" group is understood to mean a non-aromatic monocyclic or fused or non-fused polycyclic carbocycle containing from 5 to 22 carbon atoms which can comprise from one to several unsaturations.

[0058] The term “heterocycloalkyl” group is understood to mean a 5- to 22-membered, non-aromatic, monocyclic or fused or non-fused polycyclic radical comprising from 1 to 6 heteroatoms chosen from nitrogen, oxygen or sulfur atoms.

[0059] The term "polar organic solvent” is understood to mean a solvent which comprises carbon and 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 with different electronegativities and the difference in electronegativity of between 0.4 and 1.7, forming polarized bonds between them.

[0060] The term"protic solvent"is understood to mean that the polar solvents, according to a second criterion, the proticity, that is to say the capacity of the solvent to release acidic H+ions or to create hydrogen bonds, i.e. comprising generally hydroxyl or amino groups.

[0061] Mention may be made, by way of “aprotic polar organic solvent”, of di(C1-C6)alkyl ketones, such as acetone or methyl ethyl ketone, di(C1-C6)alkyl sulfoxide, such as DiMethyl SulfOxide (DMSO), (C1-C6)alkylnitrile, heterocycloalkyls and cycloalkyl(C1-C6)alkoxy compounds, such as pyridine, THF or cyclopentyl methyl ether (CPME), or (C1-C6)alkylcarbonyl(C1-C6)alkoxy compounds, such as tert-butyl acetate TBA.

[0062] Mention may be made, by way of "protic polar organic solvent, of (C2-C10)alkan(e)(poly)ols, preferably (C2-C8)alkanols, such as ethanol or 2-Methyl-2-Butanol (2M2B).

[0063] Within the meaning of the present invention, the term “geometrical isomer” is understood to denote any molecule of identical constitution to the formula in question but the spatial organization of the atoms of which is different. In particular, they can be conformational stereoisomers, that is to say compounds differing by rotation around a single bond, or configurational stereoisomers, in particular enantiomers or diastereoisomers.

[0064] The term “acid” is understood to mean an organic or inorganic substance which, when it is dissolved in water, releases proton ions (H⁺). The acid(s) can be a Brønsted or Lewis acid. The acid(s) of the invention can be organic or inorganic. In particular, the acid(s) is (are) chosen from inorganic acids, especially i) acid halides, such as hydrochloric acid; ii) organic acids, in particular sulfonic acids, including the acids: Alk-S(O)2OH; iii) the acids: Ar-S(O)2OH, such as benzenesulfonic acid and toluenesulfonic acid; iv) (poly)(hydroxy)(C1-C6)alkyl(poly)carboxylic acids, such as succinic acid, tartaric acid, lactic acid or acetic acid; v) the acids: Alk-O-S(O)OH; vi) the acids: Ar-O-S(O)OH; vii) the acids: Alk-O-S(O)2OH; viii) the acids: Ar-O-S(O)2OH;ix) the phosphoric acids O=P(OH)3and HO-[P(O)(OH)]w-P(O)(OH)2with w being an integer; x) triflic acid; xi) tetrahaloboric acids and xii) hexahalo acids Hal6PH, such as HPF6.

[0065] The term “anionic counterion” is understood to mean an anion or an anionic group resulting from an organic or inorganic acid salt which counterbalances the cationic charge of the ionic liquid IL; more particularly, the anionic counterion is chosen from: i) halides, such as chloride or bromide; ii) nitrates NO3-; iii) sulfonates, including C1-C6alkylsulfonates: Alk-S(O)2O-, such as methanesulfonate or mesylate and ethanesulfonate; 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-O-, O=P(O-)2-OH, O=P(O-)3, HO-[P(O)(O-)]w-P(O)(O-)2with w being an integer; xiv) C1-C6alkylcarboxylates: Alk-C(O)-O-, such as acetate; xv) triflate; xvi) borates, such as tetrafluoroborate; xvii) hexahalo phosphates, such as PF6-, xviii) tetrahaloborates, such as BF4-; xix) disulfate (O=)2S(O-)2or SO42-and monosulfate HSO4-; the anionic counterion, resulting from the organic or inorganic acid salt, provides the electrical neutrality of the IL molecule; in particular, the anionic counterion is an organic counterion, more particularly with a molecular molar mass MM of greater than or equal to 45 g / mol and preferably of greater than or equal to 55 g / mol.

[0066] Moreover, the addition salts which can be used in the context of the invention are in particular chosen from the addition salts with a cosmetically acceptable base, such as the basifying agents such as defined below, for example alkali metal hydroxides, for example sodium hydroxide, potassium hydroxide, aqueous ammonia, amines or alkanolamines.

[0067] Within the meaning of the present invention, the term “organic or inorganic acid or base salt” is understood to denote a salt obtained between an ionic form of the compound in question and a corresponding counterion. In particular, such a salt is obtained by addition of an organic or inorganic acid or base, which is in particular cosmetically acceptable, to the compound in question. Mention may be made, as examples of inorganic bases or inorganic alkaline bases, of hydroxides or carbonates of alkali or alkaline earth metals, such as sodium, potassium, calcium, ammonium, magnesium, lithium or sodium. Mention may be made, as examples of organic bases or organic alkaline bases, of amines or alkanolamines. Mention may be made, as examples of acids, of hydrochloric acid, hydrobromic acid, sulfuric acid, alkylsulfonic acids, arylsulfonic acids, citric acid, succinic acid, tartaric acid, lactic acid, alkoxysulfinic acids, aryloxysulfinic acids, phosphoric acid or acetic acid.

[0068] Within the meaning of the present invention, the term “solvate” is understood to denote the form of the compound in question when it is associated with a solvent. The solvates include conventional solvates formed during the process of preparation of the compound in question. Examples of solvates are those obtained in the presence of water or of a linear or branched alcohol, in particular ethanol or isopropanol.

[0069] The term “ionic liquid” or “IL” is understood to mean an organic salt comprising at least one cationic part and at least one other anionic part, it being understood that the salt comprises as many cationic group(s) as anionic group(s) in order to achieve the electrical neutrality of the molecule; preferably, the ionic liquid differs from the group of the molten salts by a melting point of less than 100°C at atmospheric pressure; in particular, the IL is liquid at ambient temperature or above, i.e. greater than or equal to 25°C, at atmospheric pressure.Preparation process

[0070] The process of the invention relates to a process for the preparation of (hetero)aromatic compound(s) substituted by a hydroxyalkylamino, preferably hydroxyethylamino, group(B)as described above, employing, during a first stage, the mixing of one or more (hetero)aromatic compound(s) having an amino group(A)as described above with i) one or more optionally substituted alkylene carbonate(s) as defined above and ii) one or more ionic liquids preferably chosen from imidazolium, triazolium and pyridinium salt(s), and then, during a second stage iii), the addition of one or more alkaline base(s), according to Scheme 1, it being understood that the process is carried out without isolating the intermediate (hetero)aromatic compound(s) substituted by a cyclic carbamate group(AB)as defined above.

[0071] Preferably, the process of the invention does not employ 2-chloroethyl chloroformate, or 2-chloroethanol, or methyl methylchlorooxoacetate, or ethylene oxide.

[0072] According to another particular embodiment, the process is a process for the preparation of aromatic compound(s) substituted by a hydroxyalkylamino group(B1), and also its organic or inorganic acid or base salts, and its solvates, such as hydrates, as described below, employing, during a first stage, the mixing of one or more aromatic compound(s) having an amino group(A1)as described below with i) one or more optionally substituted alkylene carbonate(s) as defined above and ii) one or more ionic liquid(s) preferably chosen from imidazolium, triazolium and pyridinium salt(s), and then, during a second stage iii), the addition of one or more alkaline base(s), according to Scheme 2, it being understood that the process is carried out without isolating the intermediate aromatic compound(s) substituted by a cyclic carbamate group(AB1);

[0073] [Chem. 2]

[0074] in which Scheme 2: n, p and R1to R7are as defined above.

[0075] More particularly, the process for the preparation of aromatic compound(s) substituted by a hydroxyethylamino group(B’1), and also its organic or inorganic acid or base salts, and its solvates, such as hydrates, as described below, employs, during a first stage, the mixing of one or more aromatic compound(s) having an amino group(A1)as described above with i) one or more optionally substituted ethylene carbonate(s) as defined above and ii) one or more ionic liquid(s) preferably chosen from imidazolium, triazolium and pyridinium salt(s), and then, during a second stage iii), the addition of one or more alkaline base(s), according to Scheme 3, it being understood that the process is carried out without isolating the intermediate aromatic compound(s) substituted by a cyclic carbamate group(AB'1);

[0076] [Chem. 3]

[0077] in which Scheme 3: n and R1to R7are as defined above.

[0078] More preferentially, the process of the invention is a process for the preparation of aromatic compound(s) substituted by a hydroxyalkylamino group(B2), and also its organic or inorganic acid or base salts, and its solvates, such as hydrates, as described below, employing, during a first stage, the mixing of one or more aromatic compound(s) having an amino group(A2)as described below with i) one or more optionally substituted alkylene carbonate(s) as defined above and ii) one or more ionic liquid(s) preferably chosen from imidazolium, triazolium and pyridinium salt(s), and then, during a second stage iii), the addition of one or more alkaline base(s), according to Scheme 4, it being understood that the process is carried out without isolating the intermediate aromatic compound(s) substituted by a cyclic carbamate group(AB2);

[0079] [Chem. 4]

[0080] in which Scheme 4: n, p, R2, R3and R5are as defined above.

[0081] More preferentially still, the process of the invention is a process for the preparation of aromatic compound(s) substituted by a hydroxyethylamino group(B’2), and also its organic or inorganic acid or base salts, and its solvates, such as hydrates, as described below, employing, during a first stage, the mixing of one or more aromatic compound(s) having an amino group(A2)as described above with i) one or more optionally substituted ethylene carbonate(s) as defined above and ii) one or more ionic liquid(s) preferably chosen from imidazolium, triazolium and pyridinium salt(s), and then, during a second stage iii), the addition of one or more alkaline base(s), according to Scheme 5, it being understood that the process is carried out without isolating the intermediate aromatic compound(s) substituted by a cyclic carbamate group(AB’2);

[0082] [Chem. 5]

[0083] in which Scheme 5: n, R2, R3and R5are as defined above.

[0084] The alkylene carbonate(s):

[0085] According to one embodiment, the process employs i) alkylene carbonate of following formula:

[0086]

[0087] in which p has the value 1, 2 or 3, preferably 1 or 2, and R6and R7are as defined above; preferably, R6and R7represent a hydrogen atom or R6and R7represent a (C1-C4)alkyl group, such as methyl, or else R6represents a hydrogen atom and R7represents a (C1-C4)alkyl group, or else R7represents a hydrogen atom and R6, which is identical or different if p is greater than or equal to 2, represents a hydrogen atom or a (C1-C4)alkyl group.

[0088] In particular, the process employs i) ethylene carbonate, i.e. p has the value 1, of following formula i-1):

[0089]

[0090] in which R6and R7, which are identical or different, are as defined above; preferably, R6and R7represent a hydrogen atom, i.e. of following formula i’-1):

[0091] .

[0092] According to another advantageous alternative form, the process employs i) substituted ethylene carbonate, i.e. p has the value 1, and at least one of the two radicals R6and / or R7as defined above represents a group other than a hydrogen atom; preferably, R6represents a hydrogen atom and R7represents a (C1-C4)alkyl group, such as methyl, of following formula i’’-1):

[0093]

[0094] in which R7is as defined above.

[0095] According to another alternative form of the invention, the process employs i) propylene carbonate, i.e. p has the value 2, of following formula i-2):

[0096]

[0097] in which R6and R7, which are identical or different, are as defined above; preferably, R6and R7represent a hydrogen atom or R6and R7represent a (C1-C4)alkyl group, such as methyl, or else R6represents a hydrogen atom and R7represents a (C1-C4)alkyl group, or else R7represents a hydrogen atom and R6, which is identical or different, represents a hydrogen atom or a (C1-C4)alkyl group; preferentially, R6and R7represent a hydrogen atom.

[0098] Preferably, the process employs i), i-1), i’-1), i’’-1) and i-2) of the alkylene carbonate as defined above in molar excess with respect to the molar amount of aromatic compound(s) having an amino group(A),(A1)or(A2)as defined above, i.e. n is greater than 1, preferably is of between 1 exclusive and 10 inclusive, preferentially between 2 and 8, more particularly between 3 and 6, such as 5.

[0099] The ionic liquid(s) ii)

[0100] According to one embodiment of the invention, the ionic liquid(s) is (are) solid at a temperature of greater than or equal to 40°C, indeed even solid at a temperature of greater than or equal to 60°C, more particularly solid at a temperature of greater than or equal to 80°C, in which case the ionic liquid(s) is (are) soluble in the alkylene carbonate(s) i), i-1), i’-1), i’’-1) and i-2) as defined, preferably at a temperature of greater than or equal to 40°C.

[0101] According to another advantageous embodiment of the invention, the ionic liquid(s) is (are) liquid at a temperature of less than or equal to 100°C, indeed even liquid at a temperature of less than or equal to 60°C, more particularly liquid at a temperature of less than or equal to 40°C.

[0102] During the first stage of the process for the preparation of the (hetero)aromatic compound(s) substituted by a hydroxyalkylamino group(B),(B1),(B1’),(B2)or(B2’)as defined above, a mixture of one or more (hetero)aromatic compound(s) having an amino group(A),(A1)or(A2)as defined above with i) one or more optionally substituted alkylene carbonate(s) as defined above and ii) one or more ionic liquid(s) is employed.

[0103] In particular, the IL(s) is (are) chosen from the organic salts of formula Q+X-in which Q+represents the cationic part of the molecule and X-is the anionic counterion of the molecule; in particular, the cationic part comprises at least one ammonium and / or phosphonium group and there are as many anionic counterion(s) as cationic part(s) in order to achieve the electrical neutrality of said salt. Preferentially, the salt is dissymmetric.

[0104] More particularly, the IL(s) is (are) chosen from a) ammonium salt(s), b) phosphonium salts, c) pyrrolidinium salt(s), the pyrrolidinium optionally being substituted by one or more (C1-C8)alkyl groups, d) imidazolium salt(s), the imidazolium optionally being substituted by one or more (C1-C8)alkyl groups, e) triazolium salt(s), the triazolium optionally being substituted by one or more (C1-C8)alkyl groups, and f) pyridinium salt(s), the pyridinium optionally being substituted by one or more (C1-C8)alkyl groups.

[0105] Preferentially, the IL(s) is (are) chosen from the salts of following formulae ii)-1 to ii)-6, and also their optical isomers and their tautomers:

[0106]

[0107] in which formulae ii)-1 to ii)-6:

[0108] * R10represents a (C1-C10)alkyl, in particular (C1-C8)alkyl, more particularly (C1-C6)alkyl, group, such as n-butyl;

[0109] * R11to R19, which are identical or different, represent a hydrogen atom or a (C1-C10)alkyl, in particular (C1-C8)alkyl, more particularly (C1-C6)alkyl, group, such as methyl;

[0110] * X-represents an organic or inorganic, preferably organic, anionic counterion, such as (C1-C6)alkylcarboxylate R-C(O)-O-with R representing a (C1-C6)alkyl, more particularly (C1-C4)alkyl, group, such as methyl.

[0111] More particularly, the IL(s) used in the process of the invention is (are) chosen from the salts of formulae ii)-4 and ii)-5 as defined above, more preferentially ii)-4, in which in particular R10represents a (C1-C6)alkyl, more particularly (C1-C4)alkyl, group, such as n-butyl, R11represents a (C1-C6)alkyl, more particularly (C1-C4)alkyl, group, such as methyl, R12, R14and R15, which are identical or different, are as defined above, preferably identical, in particular represent a hydrogen atom; and X-is an anionic counterion as defined above, preferably is an organic counterion, such as (C1-C6)alkylcarboxylate R-C(O)-O-with R representing a (C1-C6)alkyl, more particularly (C1-C4)alkyl, group, such as methyl.

[0112] More preferentially, the IL(s) is (are) chosen from those of following formula ii)-4’:

[0113]

[0114] in which R10, R11and R12are as defined above.

[0115] More particularly, the IL(s) of the invention is (are) chosen from those, the cationic part of which is such that:

[0116] Name of the cationic part of ii)-4 or ii)-4’AcronymR10R11R121-ethyl-3-methylimidazoliumEMIMCH3HC2H51-butyl-3-methylimidazoliumBMIMCH3HC4H91-hexyl-3-methylimidazoliumHMIMCH3HC6H131-octyl-3-methylimidazoliumOMIMCH3HC8H171-decyl-3-methylimidazoliumDMIMCH3HC10H211,3-dibutylimidazoliumBBIMC4H9HC4H91-butyl-2,3-dimethylimidazoliumBMMIMCH3CH3C4H9

[0117] Preferentially, their anionic counterion is organic and is more particularly chosen from (C1-C6)alkylcarboxylates, such as acetate CH3-C(O)-O-. More preferentially, the cation of ii)-4 or ii)-4’ is BMIM.

[0118] In particular, the molar amount added of the IL(s) i) as defined above in the first stage of the process of the invention is a catalytic amount, namely less than 1 molar equivalent (i.e. less than 100%), particularly of between 0.01 mol% and 80 mol%, more particularly of between 0.1 mol% and 60 mol%, better still of between 1% and 40%, even better still of between 2% and 20%, preferentially, between 3% and 7%, such as 5 mol%, with respect to the molar amount of the (hetero)aromatic compound(s) substituted by an amino group(A),(A1)or(A2)as defined above.

[0119] According to a particular embodiment of the invention, the first stage is carried out at a temperature of between 40°C and 200°C, more particularly of between 45°C and 180°C, better still between 50°C and 170°C, preferably between 60°C and 160°C, more preferentially between 70°C and 160°C, even better still between 80°C and 150°C, such as 135°C+ / -5°C. In particular, the mixture is left to heat during the first stage for a period of time of between 5 minutes and 24 hours, preferentially of between 30 minutes and 18 hours, more preferentially between 1 hour and 12 hours, better still between 4 hours and 8 hours, such as 6 hours+ / -60 minutes.

[0120] Preferably, the first stage is carried out with stirring.

[0121] According to one embodiment, the first stage is carried out under an inert atmosphere under argon or nitrogen.

[0122] During the second stage of the process of the invention, iii) one or more alkaline base(s), which can be chosen from inorganic or organic or hybrid alkaline agents or their mixtures, is (are) added.

[0123] The inorganic alkaline base(s) are preferably chosen from aqueous ammonia, alkali metal carbonates or bicarbonates, such as sodium carbonate or potassium carbonate and sodium bicarbonate or potassium bicarbonate, alkali metal or alkaline earth metal hydroxides, such as sodium hydroxide or potassium hydroxide, or their mixtures.

[0124] According to one embodiment of the invention, the alkaline base(s) used in stage iii) of the process are organic base(s), in particular organic amines, i.e. which contain at least one substituted or unsubstituted amino group. The organic alkaline base(s) are more preferentially chosen from organic amines, the pKbof which at 25°C is less than 12, preferably less than 10 and more advantageously still less than 6. It should be noted that it concerns the pKbcorresponding to the function which has the highest basicity. Mention may be made, as hybrid compounds, of the salts of the abovementioned amines with acids, such as carbonic acid or hydrochloric acid.

[0125] The organic alkaline base(s) used in stage iii) are, for example, chosen from alkanolamines, oxyethylenated and / or oxypropylenated ethylenediamines, amino acids and the compounds of following formula(C):

[0126]

[0127] in which formula(C):

[0128] * Wis a divalent C1-C6alkylene radical optionally substituted by a hydroxyl group or a C1-C6alkyl radical and / or optionally interrupted by one or more heteroatoms, such as oxygen or NRu;

[0129] * Rx,Ry,Rz,RtandRu, which are identical or different, represent a hydrogen atom or a C1-C6alkyl, C1-C6hydroxyalkyl or C1-C6aminoalkyl radical.

[0130] “Alkanolamine” is understood to mean an organic amine comprising a primary, secondary or tertiary amine function and one or more linear or branched C1-C8alkyl groups carrying one or more hydroxyl radicals. Alkanolamines such as mono-, di- or trialkanolamines comprising from one to three identical or different C1-C4hydroxyalkyl radicals are suitable in particular for the implementation of the invention.

[0131] Preferably, one or more alkali metal hydroxide(s), such as sodium hydroxide and / or potassium hydroxide, more preferentially potassium hydroxide, is (are) added as alkaline base(s) during the second stage iii).

[0132] In particular, the alkaline base(s) is (are) added in the form diluted in water, more particularly at a concentration by weight of between 10% and 80% of alkaline base(s) in water.

[0133] In particular, the amount of alkaline base(s) added is in molar excess with respect to the starting number of moles of (hetero)aromatic(s) substituted by an amino group(A),(A1)or(A2); preferably, the amount of alkaline base(s) in equivalent number of moles is of between 2 and 10, particularly of between 5 and 8, such as 7, equivalents of alkaline base(s) with respect to the number of moles of(A),(A1)or(A2).

[0134] In particular, the addition of the alkaline base(s) is carried out at a temperature of between 5°C and 100°C, in particular between 20°C and 80°C, such as 50°C + / - 5°C.

[0135] According to one embodiment of the mixing during the second stage is kept stirred, and / or for a period of time of between 5 minutes and 6 hours, more particularly for a period of time of between 20 minutes and 5 hours, more particularly of between 30 minutes and 4 hours, better still between 1 hour and 3 hours, such as 2 h + / - 60 minutes.

[0136] According to one embodiment, the two aqueous and organic phases are left to separate by settling, optionally followed by a dilution of the organic phase by addition of water, preferably distilled water. In particular, the dilution is carried out at a temperature of between 20°C and 60°C, such as 50°C + / - 5°C.

[0137] According to a particular embodiment of the invention, the mixture is subsequently cooled to a temperature of between 1°C and 15°C, such as 10°C + / - 1°C, preferably followed by a filtration and by one or more washing operation(s) on the precipitate (cake), preferably with a polar protic solvent, such as water, particularly distilled water, and drying, preferably under vacuum, to result in the (hetero)aromatic compound(s) substituted by a hydroxyalkylamino group(B),(B1),(B1’),(B2)or(B2’)as defined above.

[0138] According to one embodiment of the process of the invention, stage iii) is followed by one or more stage(s) of purification iv), in particular by recrystallization or precipitation, then filtration of the hydroxyalkylamino-substituted (hetero)aromatic compound(s)(B),(B1),(B1’),(B2)or(B2’)as defined above.

[0139] According to one embodiment of the process of the invention, the purification stage iv) comprises at least one stage of bringing the hydroxyalkylamino-substituted (hetero)aromatic compound(s)(B),(B1),(B1’),(B2)or(B2’)resulting from stage iii) into contact with an "activated" carbon, in one or more organic solvent(s), at least one of which is a polar aprotic organic solvent, preferably of ketone type, such as acetone.

[0140] According to a particular embodiment of the invention, the solvent employed in the purification stage iv) of the process is chosen from polar aprotic organic solvents,

[0141] more particularly of ester type, preferentially of formula (D): R7-C(O)-O-R8, in which: R7and R8, which are identical or different, represent an aromatic or non-aromatic, saturated or unsaturated, cyclic, or linear or branched, acyclic, hydrocarbon chain comprising from 1 to 10 carbon atoms, optionally interrupted by one or more heteroatom(s), such as oxygen; more preferentially, R7and R8, which are identical or different, represent a saturated, linear or branched, acyclic, hydrocarbon chain comprising between 1 and 8 carbon atoms; more preferentially still, R7and R8represent a (C1-C6)alkyl group; more particularly, R7-C(O)-O-R8is chosen from methyl acetate, propyl acetate, isopropyl acetate, butyl acetate and their mixtures.

[0142] According to a particular embodiment of the invention, the solvent employed in the purification stage iv) of the process is a polar aprotic organic solvent of ketone type, preferentially of formula (E): R7-C(O)-R8, in which R7and R8are as defined above in the formula (D); more particularly, R7-C(O)-R8is chosen from acetone, methyl ethyl ketone (MEK) and their mixtures.

[0143] According to a particular embodiment of the invention, the solvent employed in the purification stage iv) of the process is a polar aprotic organic solvent of ether type, preferentially of formula (F): R’7-O-R’8, in which R’7and R’8are as defined for R7and R8above in the formula (D); R’7and / or R’8can also represent a cycloalkyl group comprising from 3 to 10 carbon atoms, preferably 5 carbon atoms, or else R’7and R’8form, together with the oxygen atom, a saturated or unsaturated, 3- to 10-membered, preferably 5- to 7-membered, heterocycle, optionally substituted by one or more (C1-C4)alkyl groups, such as methyl; more particularly, R’7-O-R’8is chosen from diethyl ether, (di)glyme, tetrahydrofuran (THF), (C1-C4)alkyl-THF, such as methyl-THF, CycloPentyl Methyl Ether (CPME) and their mixtures.

[0144] According to a particular embodiment of the invention, the solvent employed in the purification stage iv) of the process is a polar aprotic organic solvent of amide type, preferentially of formula (G): R’7R’8N-C(O)-R9, in which R’7and R’8are as defined in the formula (F), preferably represent a (C1-C4)alkyl group, such as methyl, and R9represents a hydrogen atom or an R7group as defined above in the formula (D), preferably a hydrogen atom, R’7R’8N-C(O)-R9represents DiMethylFormamide (DMF).

[0145] Preferably, in the purification stage iv) of the process, the solvent used is a polar aprotic organic solvent of ketone type, preferentially of formula (E) as defined above, more particularly chosen from acetone.

[0146] If the mixture comprises activated carbon, it is subsequently removed, preferably by filtration.

[0147] According to one embodiment of the process of the invention, in the purification stage iv), the mixture comprising the hydroxyalkylamino-substituted (hetero)aromatic compound(s)(B),(B1),(B1’),(B2)or(B2’), optionally activated carbon and the solvent(s) is left stirring for from 1 minute to 4 hours, preferably from 30 minutes to 2 hours, more preferentially 1 hour. In particular, said mixture is heated to a temperature of greater than 30°C, more particularly up to reflux of the solvent.

[0148] In particular, the process of the invention comprises at least one purification stage iv) in which one or more inorganic or organic acid(s), preferably inorganic acid(s), in particular a halogenated acid, such as hydrochloric acid, is (are) added to the mixture comprising the hydroxyalkylamino-substituted (hetero)aromatic compound(s)(B),(B1),(B1’),(B2)or(B2’)and the organic solvent(s) as defined above. The acid(s) is (are) diluted in water, preferably distilled water.

[0149] Preferably, the addition of the acid(s) as defined above to the mixture comprising the hydroxyalkylamino-substituted (hetero)aromatic compound(s)(B),(B1),(B1’),(B2)or(B2’)and the organic solvent(s) as defined above is carried out at a temperature of less than or equal to 80°C, in particular of less than or equal to 60°C, more particularly of less than or equal to 50°C, preferably at a temperature of between 20°C and 50°C, such as 35°C + / - 5°C.

[0150] After addition of the acid(s) as defined above, the mixture comprising the hydroxyalkylamino-substituted (hetero)aromatic compound(s)(B),(B1),(B1’),(B2)or(B2’), the organic solvent(s) as defined above and the inorganic or organic acid(s) is cooled to a temperature of less than 20°C, preferably of less than or equal to 10°C, more preferentially of less than or equal to 5°C, such as 0°C + / - 2°C, until the appearance of a solid, which is withdrawn, preferably by filtration; said solid is preferably washed with a polar aprotic organic solvent, followed by drying, preferably under vacuum, to result in the hydrated acid salt as defined above.

[0151] Preferably, the reactant(A)is an aniline. i.e. in whichX1,X2,X3,X4andX5, which are identical or different, represent a group: CR1, CR2, CR3, CR4or CR5, or an aniline chosen from(A1),(A’1),(A2)and(A’2)in which:

[0152] * R1, R2, R3, R4and R5represent a hydrogen atom; or

[0153] * R1, R4and R5represent a hydrogen atom, R2represents a hydroxyl group and R3represents a (C1-C4)alkyl group, such as methyl; or

[0154] * R1, R3and R4represent a hydrogen atom, R2and R5, which are identical or different, represent a (C1-C4)alkoxy group, such as methoxy; or

[0155] * R1, R4and R5represent a hydrogen atom and R2and R3form, together with the carbon atoms which carry them, a fused 5- to 6-membered monocyclic heterocycle comprising one or more heteroatoms chosen from O and N, preferably one or two O atoms; preferably, R2and R3together form a methylenedioxy or ethylenedioxy group, more preferentially a methylenedioxy group.

[0156] More preferentially, the reactant(A),(A’1),(A1),(A2)or(A’2)is chosen from:

[0157]

[0158] to result, according to the process of the invention, in the following preferred reaction products(B),(B1),(B’1),(B2)or(B2’):

[0159]

[0160] more preferentiallyB-(4).

[0161] The following examples serve to illustrate the invention without, however, exhibiting a limiting nature.Examples

[0162] Example 1:Synthesis of the compoundB-(4)N-2-hydroxyethyl-3,4-methylenedioxyaniline:

[0163]

[0164] Ethylene carbonate (321 g, 3.65 mol, 5 equiv.) is introduced into a reactor preheated to 50°C. The mixture is brought to 135°C. 1-Butyl-3-methylimidazolium acetate (7.2 g, 0,04 mol, 0.05 equiv.) and then 3,4-(methylenedioxy)aniline (100 g, 0.73 mol, 1 equiv.) are introduced into the reaction mixture at 135°C. After stirring for 6 hours, the mixture is cooled to 60°C. Water (200 ml) and then potassium hydroxide as a 50% aqueous solution (573 g, 5.1 mol, 7 equiv.) are added at 60°C. After stirring for 2 h, the two phases are separated by settling. The organic phase is diluted in 300 ml of water while maintaining a temperature of 50°C. After cooling to 10°C, followed by filtration, by washing of the cake with water and by drying under vacuum, 2-(1,3-benzodioxol-5-ylamino)ethanol is isolated with a yield of 85%. 2-(1,3-Benzodioxol-5-ylamino)ethanol (100 g, 0.55 mol, 1 equiv.) and 2 g of activated carbon are stirred in acetone (300 ml) at 45°C for 1 h. After filtration, the liquors are acidified at 35°C by addition of 50 ml of a 37% aqueous hydrochloric acid solution. After cooling to 0°C, the solid is filtered off, washed with acetone and dried under vacuum to result in 2-(1,3-benzodioxol-5-ylamino)ethanol hydrochloride with a yield of 80%. 2-(1,3-Benzodioxol-5-ylamino)ethanol hydrochloride (100 g, 0.46 mol, 1 equiv.) is stirred in 80 ml of water at 60°C for 30 min. After filtration, the liquors are acidified at 40°C by addition of 100 ml of a 37% aqueous hydrochloric acid solution. After cooling to 0°C, the solid is filtered off, washed with acetone and dried under vacuum to result in 2-(1,3-benzodioxol-5-ylamino)ethanol hydrochloride with a yield of 80% and with an HPLC purity of greater than 99%.

[0165] It is possible to synthesize the compoundsB-(1),B-(2)andB-(3)by replacing the 3,4-methylenedioxyanilineA-(4)of the experimental protocol of Example 1 with the anilinesA-(1),A-(2)andA-(3)respectively.

[0166] B-(1) B-(2) B-(3) A-(1)N-2-hydroxyethylaniline:A-(2)N-2-hydroxyethyl-3-hydroxy-4-methylanilineA-(3)N-2-hydroxyethyl-3,6-dimethoxyaniline

Claims

Process for the preparation of one or more (hetero)aromatic compound(s) substituted by a hydroxyalkylamino group(B), and also its organic or inorganic acid or base salts, and its solvates, such as hydrates, employing, during a first stage, the mixing of one or more (hetero)aromatic compound(s) having an amino group(A)withi) one or more optionally substituted alkylene carbonate(s); andii) one or more ionic liquid(s); theniii) during a second stage iii), the addition of one or more alkaline base(s), according to Scheme 1;it being understood that the process is carried out without isolating the intermediate (hetero)aromatic compound(s) substituted by a cyclic carbamate group(AB):Scheme 1, in which(A),(B)and(AB):* nrepresents the molar equivalent number, preferably is of between 1 and 10, preferentially between 2 and 8 and more particularly between 3 and 6, such as 5;* pis an integer of between 1 and 5; in particular, p has the value 1 or 2, preferentially p has the value 1;* X1,X2,X3,X4andX5, which are identical or different, represent a group or atom: CR1or N, CR2or N, CR3or N, CR4or N, and CR5or N respectively with:R1, R2, R3, R4and R5, which are identical or different, represent an atom or group chosen from:a) hydrogen,b) halogen,c) nitro(so),d) cyano,e) hydroxy,f) (C1-C6)alkyl optionally substituted by at least one atom or group chosen from: 1) halogen, 2) hydroxy, 3) (di)(C1-C4)(alkyl)amino and 4) (C1-C4)alkoxy,g) (C1-C6)alkoxy, the alkyl part of the alkoxy of which can optionally be substituted by one or more atom(s) or group(s) chosen from i) to iv) as defined above,h) amino RaRbN- with Raand Rb, which are identical or different, representing a hydrogen atom or a (C1-C6)alkyl group, or else two groups Raand Rbform, together with the nitrogen atom which carries them, a saturated or unsaturated, 4- to 6-membered, preferably 5- or 6-membered, heterocycle, such as morpholino, piperazino or piperidino, optionally substituted by one or more (C1-C4)alkyl group(s), such as methyl;i) two contiguous groups R1and R2, and / or R2and R3, and / or R3and R4, and / or R4and R5form, together with the carbon atoms which carry them, a saturated or unsaturated, non-aromatic or aromatic, 4- to 6-membered, preferably 5- or 6-membered, heterocycle or carbocycle optionally substituted by one or more atom(s) or group(s) chosen from: a) to g) as defined above, more particularly a 5-membered heterocycle preferably comprising from 1 to 3 oxygen or nitrogen, preferably oxygen, atoms;j) carboxy(late) -C(O)-ORwith Rrepresenting a hydrogen atom, a cationic counterion, such as alkali metal or alkaline earth metal, or a (C1-C6)alkyl group;preferably,X1toX5, which are identical or different, represent a CR1, CR2, CR3, CR4and CR5group; more particularly, R1to R5represent a hydrogen atom or a group chosen from a) hydroxy, f) (C1-C6)alkyl, or g) (C1-C6)alkoxy, or else k) two contiguous groups R1and R2, or R2and R3, or R3and R4, or R4and R5, preferably R2and R3,form, together with the carbon atoms which carry them, a 5-membered heterocycle preferably comprising from 1 to 3 oxygen atoms; preferably, R1represents a hydrogen atom, R2represents a hydrogen atom or a (C1-C4)alkoxy group, such as methoxy, R3represents a hydrogen atom or a (C1-C4)alkyl group, R4represents a hydrogen atom or a hydroxyl group and R5represents a hydrogen atom or a (C1-C4)alkoxy group, or else R2and R3together form a methylenedioxy or ethylenedioxy, preferably methylenedioxy, group; and* R6andR7, which are identical or different, represent a hydrogen atom or group chosen from (C1-C6)alkyl, such as methyl, (C1-C6)alkoxy, aryloxy, such as phenoxy, or aryloxy(C1-C6)alkyl, particularly phenoxy(C1-C4)alkyl, such as phenoxymethyl, preferably,R6andR7represent a hydrogen atom or a (C1-C4)alkyl group, such as methyl.Process according to the preceding claim, in whichX1,X2,X3,X4andX5, which are identical or different, represent a group or an atom: CR1or N, CR2or N, CR3or N, CR4or N, and CR5or N respectively, it being understood that at least one ofX1,X2,X3,X4andX5represents a nitrogen atom N, preferably one, two or three at most ofX1,X2,X3,X4andX5represent(s) 1, 2 or 3 nitrogen atom(s), preferably 1 nitrogen atom.Process according to the preceding claim, in which one or more aromatic compound(s) substituted by a hydroxyalkylamino group(B1), and also its organic or inorganic acid or base salts, and its solvates, such as hydrates, employing, during a first stage, the mixing of one or more aromatic compound(s) having an amino group(A1)as described below with i) one or more optionally substituted alkylene carbonate(s) as defined above and ii) one or more ionic liquid(s) preferably chosen from imidazolium, triazolium and pyridinium salt(s), and then, during a second stage iii), the addition of one or more alkaline base(s), according to Scheme 2, it being understood that the process is carried out without isolating the intermediate aromatic compound(s) substituted by a cyclic carbamate group(AB1); in which Scheme 2: n, p and R1to R7are as defined in Claim 1.Process according to Claim 1 or 3 for the preparation of aromatic compound(s) substituted by a hydroxyethylamino group(B’1), and also its organic or inorganic acid or base salts, and its solvates, such as hydrates, as described below, employing, during a first stage, the mixing of one or more aromatic compound(s) having an amino group(A1)as described in the preceding claim with i) one or more optionally substituted ethylene carbonate(s) and ii) one or more ionic liquid(s), then iii), during a second stage, the addition of one or more alkaline base(s), according to Scheme 3, it being understood that the process is carried out without isolating the intermediate aromatic compound(s) substituted by a cyclic carbamate group(AB'1); in which Scheme 3: n and R1to R7are as defined in Claim 1 or 3;Process according to Claim 1, 3 or 4 for the preparation of aromatic compound(s) substituted by a hydroxyalkylamino group(B2), and also its organic or inorganic acid or base salts, and its solvates, such as hydrates, as described below, employing, during a first stage, the mixing of one or more aromatic compound(s) having an amino group(A2)as described below with i) one or more optionally substituted alkylene carbonate(s) and ii) one or more ionic liquid(s) preferably chosen from imidazolium, triazolium and pyridinium salt(s), and then, during a second stage iii), the addition of one or more alkaline base(s), according to Scheme 4, it being understood that the process is carried out without isolating the intermediate aromatic compound(s) substituted by a cyclic carbamate group(AB2); in which Scheme 4: n, p, R2, R3and R5are as defined above;more preferentially, the process for the preparation of aromatic compound(s) substituted by a hydroxyethylamino group(B’2), and also its organic or inorganic acid or base salts, and its solvates, such as hydrates, as described below, employs, during a first stage, the mixing of one or more aromatic compound(s) having an amino group(A2)as described above with i) one or more optionally substituted ethylene carbonate(s) and ii) one or more ionic liquid(s) preferably chosen from imidazolium, triazolium and pyridinium salt(s), and then, during a second stage iii), the addition of one or more alkaline base(s), according to Scheme 5, it being understood that the process is carried out without isolating the intermediate aromatic compound(s) substituted by a cyclic carbamate group(AB’2); in which Scheme 5: n, R2, R3and R5are as defined above.Process according to any one of the preceding claims, which employs i) alkylene carbonate of following formula:in which p has the value 1, 2 or 3, preferably 1 or 2, and R6and R7are as defined above; preferably, R6and R7represent a hydrogen atom or R6and R7represent a (C1-C4)alkyl group, such as methyl, or else R6represents a hydrogen atom and R7represents a (C1-C4)alkyl group, or else R7represents a hydrogen atom and R6, which is identical or different if p is greater than or equal to 2, represents a hydrogen atom or a (C1-C4)alkyl group.Process according to any one of the preceding claims, which employs i) ethylene carbonate, i.e. p has the value 1, of following formula i-1):in which R6and R7, which are identical or different, are as defined above; preferably, R6and R7represent a hydrogen atom, i.e. of following formula i’-1):preferably, i) the ethylene carbonate is substituted, i.e. p has the value 1 and at least one of the two radicals R6and / or R7as defined above represents a group other than a hydrogen atom; preferably, R6represents a hydrogen atom and R7represents a (C1-C4)alkyl group, such as methyl, of following formula i’’-1):in which R7is as defined above.Process according to any one of the preceding claims, which employs i) propylene carbonate, i.e. p has the value 2, of following formula i-2):in which R6and R7, which are identical or different, are as defined above; preferably, R6and R7represent a hydrogen atom or R6and R7represent a (C1-C4)alkyl group, such as methyl, or else R6represents a hydrogen atom and R7represents a (C1-C4)alkyl group, or else R7represents a hydrogen atom and R6, which is identical or different, represents a hydrogen atom or a (C1-C4)alkyl group; preferentially, R6and R7represent a hydrogen atom.Process according to any one of the preceding claims, which employs alkylene carbonate i), i-1), i’-1), i’’-1) and i-2) as defined above in molar excess with respect to the molar amount of aromatic compound(s) having an amino group(A),(A1)or(A2)as defined in any one of the preceding claims, i.e. n is greater than 1, preferably is of between 1 exclusive and 10 inclusive, preferentially between 2 and 8, more particularly between 3 and 6, such as 5.Process according to any one of the preceding claims, which employs one or more ionic liquid(s) IL(s) chosen from the organic salts of formula Q+X-in which Q+represents the cationic part of the molecule and X-is the anionic counterion of the molecule; in particular, the cationic part comprises at least one ammonium and / or phosphonium group and comprising as many anionic counterion(s) as cationic part(s) in order to achieve the electrical neutrality of said salt; preferentially, the salt is dissymmetric; more particularly, the IL(s) is (are) chosen from a) ammonium salt(s), b) phosphonium salts, c) pyrrolidinium salt(s), the pyrrolidinium optionally being substituted by one or more (C1-C8)alkyl groups, d) imidazolium salt(s), the imidazolium optionally being substituted by one or more (C1-C8)alkyl groups, e) triazolium salt(s), the triazolium optionally being substituted by one or more (C1-C8)alkyl groups, and f) pyridinium salt(s), the pyridinium optionally being substituted by one or more (C1-C8)alkyl groups.Process according to any one of the preceding claims, which employs one or more ionic liquid(s) IL(s) chosen from the salts of following formulae ii)-1 to ii)-6, and also their optical isomers and their tautomers:in which formulae ii)-1 to ii)-6:* R10represents a (C1-C10)alkyl, in particular (C1-C8)alkyl, more particularly (C1-C6)alkyl, group, such as n-butyl;* R11to R19, which are identical or different, represent a hydrogen atom or a (C1-C10)alkyl, in particular (C1-C8)alkyl, more particularly (C1-C6)alkyl, group, such as methyl;* X-represents an organic or inorganic, preferably organic, anionic counterion, such as (C1-C6)alkylcarboxylate R-C(O)-O-with R representing a (C1-C6)alkyl, more particularly (C1-C4)alkyl, group, such as methyl; in particular, the ionic liquid(s) IL(s) is (are) chosen from the salts of formulae ii)-4 and ii)-5 as defined above, more preferentially ii)-4, in which in particular R10represents a (C1-C6)alkyl, more particularly (C1-C4)alkyl, group, such as n-butyl, R11represents a (C1-C6)alkyl, more particularly (C1-C4)alkyl, group, such as methyl, R12, R14and R15, which are identical or different, are as defined above, preferably identical, more particularly still represent a hydrogen atom; and X-is an anionic counterion as defined above, preferably is an organic counterion, such as (C1-C6)alkylcarboxylate R-C(O)-O-with R representing a (C1-C6)alkyl, more particularly (C1-C4)alkyl, group, such as methyl; preferentially, the IL(s) is (are) chosen from those of following formula ii)-4’:in which R10, R11and R12are as defined above; more preferentially, the IL(s) is (are) chosen from those, the cationic part of which is such that:Name of the cationic part of ii)-4 or ii)-4’AcronymR10R11R121-ethyl-3-methylimidazoliumEMIMCH3HC2H51-butyl-3-methylimidazoliumBMIMCH3HC4H91-hexyl-3-methylimidazoliumHMIMCH3HC6H131-octyl-3-methylimidazoliumOMIMCH3HC8H171-decyl-3-methylimidazoliumDMIMCH3HC10H211,3-dibutylimidazoliumBBIMC4H9HC4H91-butyl-2,3-dimethylimidazoliumBMMIMCH3CH3C4H9preferentially, their anionic counterion is organic and is more preferentially chosen from (C1-C6)alkylcarboxylates, such as acetate CH3-C(O)-O-; better still, the cation of ii)-4 or ii)-4’ is BMIM.Process according to any one of the preceding claims, which employs one or more ionic liquid(s) i) in an amount of less than 1 molar equivalent, particularly of between 0.01 mol% and 80 mol%, more particularly of between 0.1 mol% and 60 mol%, better still of between 1% and 40%, even better still of between 2% and 20%, preferentially, between 3% and 7%, such as 5 mol%, with respect to the molar amount of the (hetero)aromatic compound(s) substituted by an amino group(A),(A1)or(A2).Process according to any one of the preceding claims, the first stage of which is carried out at a temperature of between 40°C and 200°C, more particularly of between 45°C and 180°C, better still between 50°C and 170°C, preferably between 60°C and 160°C, more preferentially between 70°C and 160°C, even better still between 80°C and 150°C, such as 135°C+ / -5°C; in particular, the mixture is left to heat during the first stage for a period of time of between 5 minutes and 24 hours, preferentially of between 30 minutes and 18 hours, more preferentially between 1 hour and 12 hours, better still between 4 hours and 8 hours, such as 6 hours+ / -60 minutes.Process according to any one of the preceding claims, in which, during the second stage, iii) one or more alkaline base(s) chosen from inorganic or organic or hybrid alkaline agent(s), or their mixtures, preferably chosen from aqueous ammonia, alkali metal carbonates or bicarbonates, such as sodium carbonate or potassium carbonate and sodium bicarbonate or potassium bicarbonate, alkali metal or alkaline earth metal hydroxides, such as sodium hydroxide or potassium hydroxide, or their mixtures, is (are) added; preferably, during the second stage, iii) one or more alkali metal hydroxide(s), such as sodium hydroxide and / or potassium hydroxide, more preferentially potassium hydroxide, is (are) added; more preferentially, the alkaline base(s) is (are) added in the form diluted in water, more particularly at a concentration by weight of between 10% and 80% of alkaline base(s) in water.Process according to any one of the preceding claims, in which the amount of alkaline base(s) added is in molar excess with respect to the starting number of moles of (hetero)aromatic(s) substituted by an amino group(A),(A1)or(A2); preferably, the amount of alkaline base(s) in equivalent number of moles is of between 2 and 10, particularly of between 5 and 8, such as 7, equivalents of alkaline base(s) with respect to the number of moles of(A),(A1)or(A2).Process according to any one of the preceding claims, in which the addition of the alkaline base(s) is carried out at a temperature of between 5°C and 100°C, in particular between 20°C and 80°C, such as 50°C + / - 5°C, and / or the second stage is kept stirred for a period of time of between 5 minutes and 6 hours, more particularly for a period of time of between 20 minutes and 5 hours, more particularly of between 30 minutes and 4 hours, better still between 1 hour and 3 hours, such as 2 h + / - 60 minutes.Process according to any one of Claims 14 to 16, in which the two aqueous and organic phases are left to separate by settling, optionally followed by a dilution of the organic phase by addition of water, preferably distilled water. In particular, the dilution is carried out at a temperature of between 20°C and 60°C, such as 50°C + / - 5°C.Process according to the preceding claim, in which the mixture is subsequently cooled to a temperature of between 1°C and 15°C, such as 10°C + / - 1°C, preferably followed by a filtration and by one or more washing operation(s) on the precipitate (cake), preferably with a polar protic solvent, such as water, particularly distilled water, and drying, preferably under vacuum, to result in the (hetero)aromatic compound(s) substituted by a hydroxyalkylamino group(B),(B1),(B1’),(B2)or(B2’)as defined in any one of the preceding claims.Process according to any one of the preceding claims, in which stage iii) is followed by one or more stage(s) of purification iv), in particular by recrystallization or precipitation, then filtration of the hydroxyalkylamino-substituted (hetero)aromatic compound(s)(B),(B1),(B1’),(B2)or(B2’)as defined in any one of the preceding claims; preferentially, the purification stage iv) comprises at least one stage of bringing the hydroxyalkylamino-substituted (hetero)aromatic compound(s)(B),(B1),(B1’),(B2)or(B2’)resulting from stage iii) into contact with optionally an "activated" carbon, in one or more organic solvent(s), at least one of the solvents of which is a polar aprotic organic solvent, preferably of ketone type, such as acetone; if the mixture comprises activated carbon, it is subsequently removed, preferably by filtration.Process according to the preceding claim, which comprises at least one purification stage iv) in which one or more inorganic or organic acid(s), preferably inorganic acid(s), in particular a halogenated acid, such as hydrochloric acid, is (are) added to the mixture comprising the hydroxyalkylamino-substituted (hetero)aromatic compound(s)(B),(B1),(B1’),(B2)or(B2’)and the organic solvent(s) as defined above; the acid(s) is (are) diluted in water, preferably distilled water; more preferentially, after addition of the acid(s) as defined above, the mixture comprising the hydroxyalkylamino-substituted (hetero)aromatic compound(s)(B),(B1),(B1’),(B2)or(B2’), the organic solvent(s) as defined above and the inorganic or organic acid(s) is cooled to a temperature of less than 20°C, preferably of less than or equal to 10°C, more preferentially of less than or equal to 5°C, such as 0°C + / - 2°C, until the appearance of a solid, which is withdrawn, preferably by filtration; said solid is preferably washed with a polar aprotic organic solvent, followed by drying, preferably under vacuum, to result in the hydrated or non-hydrated organic or inorganic acid salt as defined above.Process according to any one of the preceding claims, in which the reactant(A)is an aniline. i.e. in whichX1,X2,X3,X4andX5, which are identical or different, represent a group: CR1, CR2, CR3, CR4or CR5, or an aniline chosen from(A1),(A’1),(A2)and(A’2)in which:* R1, R2, R3, R4and R5represent a hydrogen atom; or* R1, R4and R5represent a hydrogen atom, R2represents a hydroxyl group and R3represents a (C1-C4)alkyl group, such as methyl; or* R1, R3and R4represent a hydrogen atom, R2and R5, which are identical or different, represent a (C1-C4)alkoxy group, such as methoxy; or* R1, R4and R5represent a hydrogen atom and R2and R3form, together with the carbon atoms which carry them, a fused 5- to 6-membered monocyclic heterocycle comprising one or more heteroatoms chosen from O and N, preferably one or two O atoms; preferably, R2and R3together form a methylenedioxy or ethylenedioxy group, more preferentially a methylenedioxy group;more preferentially, the reactant(A),(A’1),(A1),(A2)or(A’2)is chosen from:to result, according to the process of the invention, in the following preferred reaction products(B),(B1),(B’1),(B2)or(B2’):more preferentiallyB-(4).

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