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WO2025099119A1 - Nouvelle synthèse télescopique hautement économique de 2-méthoxyméthyl-p-phénylènediamine - Google Patents

Nouvelle synthèse télescopique hautement économique de 2-méthoxyméthyl-p-phénylènediamine Download PDF

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WO2025099119A1
WO2025099119A1 PCT/EP2024/081428 EP2024081428W WO2025099119A1 WO 2025099119 A1 WO2025099119 A1 WO 2025099119A1 EP 2024081428 W EP2024081428 W EP 2024081428W WO 2025099119 A1 WO2025099119 A1 WO 2025099119A1
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methoxymethyl
aniline
azo
methanol
acid
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Markus Speckbacher
Armin Osan
Heike ABEL
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Wella Germany GmbH
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Wella Germany GmbH
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
    • C07C303/02—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of sulfonic acids or halides thereof
    • C07C303/22—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of sulfonic acids or halides thereof from sulfonic acids, by reactions not involving the formation of sulfo or halosulfonyl groups; from sulfonic halides by reactions not involving the formation of halosulfonyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
    • C07C201/06—Preparation of nitro compounds
    • C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
    • C07C205/27—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by etherified hydroxy groups
    • C07C205/34—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by etherified hydroxy groups having nitro groups bound to carbon atoms of six-membered aromatic rings and etherified hydroxy groups bound to acyclic carbon atoms of the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
    • C07C209/68—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton
    • C07C209/74—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton by halogenation, hydrohalogenation, dehalogenation, or dehydrohalogenation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C211/00—Compounds containing amino groups bound to a carbon skeleton
    • C07C211/43—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
    • C07C211/44—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having amino groups bound to only one six-membered aromatic ring
    • C07C211/52—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having amino groups bound to only one six-membered aromatic ring the carbon skeleton being further substituted by halogen atoms or by nitro or nitroso groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
    • C07C213/02—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
    • C07C213/06—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton from hydroxy amines by reactions involving the etherification or esterification of hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
    • C07C217/76—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings and etherified hydroxy groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
    • C07C309/01—Sulfonic acids
    • C07C309/02—Sulfonic acids having sulfo groups bound to acyclic carbon atoms
    • C07C309/03—Sulfonic acids having sulfo groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
    • C07C309/13—Sulfonic acids having sulfo groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton containing nitrogen atoms, not being part of nitro or nitroso groups, bound to the carbon skeleton
    • C07C309/14—Sulfonic acids having sulfo groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton containing nitrogen atoms, not being part of nitro or nitroso groups, bound to the carbon skeleton containing amino groups bound to the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
    • C07C309/01—Sulfonic acids
    • C07C309/28—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C309/45—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing nitrogen atoms, not being part of nitro or nitroso groups, bound to the carbon skeleton
    • C07C309/46—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing nitrogen atoms, not being part of nitro or nitroso groups, bound to the carbon skeleton having the sulfo groups bound to carbon atoms of non-condensed six-membered aromatic rings

Definitions

  • the present invention relates to a new cost efficient and environmentally friendly telescoping synthesis of 2-methoxymethyl-p-phenylenediamine according to formula (I) or salts thereof, also known under the abbreviation MBS (COLIPA n“ A160).
  • MBS COLIPA n“ A160
  • This compound is known to the Industry as low sensitizing major dye precursor used in oxidative hair dye compositions as replacement for traditional p-phenylenediamine or p-toluenediamine dye precursors.
  • p-phenylenediamine derivatives are key precursors for oxidative hair dyeing. They are usually used to generate dark shades, p-phenylenediamine derivatives have been used for decades for hair dyeing.
  • p-phenylenediamine derivatives a particularly favorable candidate, namely 2- methoxymethyl-p-phenylenediamine has been identified.
  • This dye precursor is particularly advantageous in that it is typically characterized by a lower sensitizing potential than traditional p- phenylenediamine or p-toluenediamine dye precursors.
  • US2003/0041392A1 discloses a process for the preparation of 2-methoxymethyl-p- phenylenediamine (I) via a Smiles rearrangement in one of the intermediate steps. Disadvantages of the process are harsh reaction conditions and the use of reactants such as trioxane (formaldehyde trimer) which may create health hazards for the workers in the production line. In addition, the process produces large amounts of waste solvent solutions containing sulfuric acid or toluene. These solutions cannot be recycled for the process but have to be discarded. Yields for the process according to US2003/0041392A1 are in the order of 50% of theoretical.
  • the carbon balance is insufficient, since the reactant benzylamine merely contributes a nitrogen atom, while the remainder of the molecule is discarded in the form of toluene-containing mixtures.
  • a particular disadvantage of this method is that the product obtained comprises amorphous material which may lead to unwanted side effects such as surface oxidation. Surface oxidation in turn may negatively impact the appearance of the powdered material which can be a success criteria for cosmetic applications/formulations.
  • 2-methoxymethyl-2-phenylenediamine (I) can be prepared via a facile and commercially offerede 4-step synthesis involving a careful selection of novel azo intermediates, not previously known to the literature, followed by low cost and environmentally friendly methods to cleave the azo intermediate which may involve formate salts, metal catalysts, classic hydrogen sources such as hydrogen or hydrazine, or also electrochemical hydrogenation methods via electrolysis, to yield a 1:1 mixture of cleavage products, with one of them being the desired 2-methoxymethyl-2-phenylenediamine (I).
  • the cleavage products are easily to separate with standard methods such as liquid extraction etc., due to significant differences in polarity of both cleavage products.
  • Subject matter of the present invention is a method for preparing 2-methoxymethyl-p- phenylenediamine (I), or a salt thereof, or mixture thereof, as defined in claim 1.
  • the dependent claims relate to particular embodiments thereof. Further subject matter of the present invention are novel intermediates, as defined in claim 15,
  • the method according to the present invention for preparing 2-methoxymethyl-p-phenylenediamine or a salt thereof, or mixture thereof, comprises the following steps:
  • Aromatic amine (VI) may then be reused, and may for example be recycled to the diazotation campaign.
  • aromatic amine (VII) is not particularly critical, and a wide variety of compounds may be used as the aromatic amine (VI). It is preferred, however, that the polarity of 2- methoxymethyl-p-phenylenediamine (I) and the polarity of aromatic amine (VI) differ significantly, as such difference in polarity facilitates separating 2-methoxymethyl-p-phenylenediamine (I) and aromatic amine (VI) in the final step of the method according to the present invention.
  • the polarity of 2-methoxymethyl-p-phenylenediamine (II), expressed in terms of the partition coefficient LogPow is -0.49, determined according to EU Method A.8 at pH 7.
  • the partition coefficient logPow of aromatic amine (VI), as determined by EU method A.8, according to a preferred embodiment is less than -1,5, for example less than -2, such as less than -3.
  • the aromatic moiety of the aromatic amines (VI) having the formula H2N-R1 may be selected, for example, from aromatic moieties R2 to R15:
  • Preferred aromatic amines (VI) include the ones having acidic moieties, for example R2-NH2, R3- NH2, R10-NH2, R14-NH2, R15-NH2, Another preferred aromatic amine (VI) comprises phthalic acid as the aromatic moiety. Also preferred, but less preferred are aromatic amines (VI) with nitro groups, such as R11-NH2,
  • a particular preferred aromatic amine (VI) having the formula NH2-R1 is sulfanilic acid (IX).
  • 2-(methoxymethyl)aniline (IV) may be provided by : methylating o-nitro-benzyl alcohol (II) to form 2-methoxymethyl-nitrobenzene (III) reducing 2-methoxymethyl-nitrobenzene (III) to form 2-(methoxymethyl)aniline (IV),
  • 2-(methoxymethyl)aniline (IV) may be provided by : reacting o-toluidine (II)* with chlorine gas, to form o-amino-benzyl chloride (II)**
  • 2-(methoxymethyl)aniline (IV) may be provided by ; reducing o-nitro-benzyl alcohol (II) to form 2-amino-benzyl alcohol (II) * * * and methylating o-amino-benzyl alcohol (II)*** to form 2-(methoxymethyl)aniline (IV).
  • the methylation may be carried out using methanol in sulfuric acid.
  • step (b) of the method according to the present invention comprises adding an aqueous solution of hydroxymethanesulfonate to a solution of 2- (methoxymethyl)aniline (IV) in methanol, ethanol, isopropanol, n-propanol, or a mixture thereof, or in an aqueous solution comprising at least 50 wt% methanol, ethanol, isopropanol, n-propanol, or a mixture thereof, in particular a solution of 2-(methoxymethyl)aniline (IV) in methanol.
  • such aqueous solutions comprise at least 80 wt% methanol, ethanol, isopropanol, n- propanol, or a mixture thereof, for example at least 90 wt% methanol, ethanol, isopropanol, n- propanol, or a mixture thereof.
  • the method further comprises cooling the reaction mixture to precipitate [2-methoxymethyl-anilino]methane sulfonate (V).
  • step (b) further comprises separating precipitated [2-methoxymethyl- anilino]methane sulfonate (V).
  • step (c) comprises diazotizing aromatic amine (VI) in aqueous solution in the presence of a nitrosation agent under acidic conditions.
  • the nitrosation agent my be selected, for example, from sodium nitrite, potassium nitrite, dinitrogen pentoxide, nitrosyl sulfuric acid, and mixtures thereof.
  • the method further comprises adding the diazonium salt solution to (V) in methanol, ethanol, isopropanol, n-propanol, or a mixture thereof, or in an aqueous solution comprising at least 50 wt% methanol, ethanol, isopropanol, n-propanol, or a mixture thereof.
  • aqueous solutions comprise at least 80 wt% methanol, ethanol, isopropanol, n-propanol, or a mixture thereof, for example at least 90 wt% methanol, ethanol, isopropanol, n-propanol, or a mixture thereof.
  • the method further comprises precipitating (VII) by salting out.
  • step (c) further comprises separating 4-azo-2-methoxymethyl-(sulfomethyl)aniline (VII).
  • step (d ) is carried out in alkaline medium.
  • Step (d) further may comprise adding an aqueous alkaline solution to a suspension of 4-azo-2-methoxymethyl- (sulfomethyl)aniline (VII) in methanol, ethanol, isopropanol, n-propanol, or a mixture thereof, or in an aqueous solution comprising at least 50 wt% methanol, ethanol, isopropanol, n-propanol, or a mixture thereof.
  • VI 4-azo-2-methoxymethyl- (sulfomethyl)aniline
  • such aqueous solutions comprise at least 80 wt% methanol, ethanol, isopropanol, n-propanol, or a mixture thereof, for example at least 90 wt% methanol, ethanol, isopropanol, n-propanol, or a mixture thereof.
  • the method further may comprise acidifying the reaction mixture with at least one mineral or organic acid to precipitate 4-azo-2-(methoxymethyl Jan i line (VIII).
  • the method further may comprise filtering off 4-azo-2-( methoxy methyl)aniline (VIII).
  • Cleaving 4-azo-2-(methoxymethyl)aniline (VIII) under reducing conditions to give 2-methoxymethyl- p-phenylenediamine (I) and aromatic amine (VI) according to step (e) of the inventive method typically is carried out using a hydrogen source in the presence of metal catalyst, in particular using as the hydrogen source ammonium formate, hydrazine hydrate and/or H2.
  • the hydrogen source is ammonium formate and the metal catalyst is Pd/C.
  • step (e) may be carried out using an electrochemical method.
  • the solvent used in step (e) is methanol, ethanol, isopropanol, methyl acetate, ethyl acetate, toluol or a mixture thereof.
  • the method may further comprise cooling the reaction mixture, and filtering the reaction mixture to obtain a solution of 2-methoxymethyl-p-phenylenediamine (I).
  • the precipitate from the filter will be collected to recover metal catalyst and aromatic amine (VI).
  • aromatic amine (VI) may be recycled to step (c).
  • 2-methoxymethyl-p-phenylenediamine (I) conveniently is recovered from the solution obtained above. Separating 2-methoxymethyl-p-phenylenediamine (I) typically may comprise concentrating the solution by distilling-off solvent, and adding a non-polar organic solvent to precipitate 2- methoxymethyl-p-phenylenediamine (II). According to a particular embodiment, the non-polar organic solvent is toluene. The solvent d isti lled-off in the concentrating step conveniently is recycled.
  • the method according to the present invention provides a facile synthesis concept which fulfills the requirements of a green synthesis using mainly aqueous reaction solutions and avoid unnecessary heating steps wherever possible.
  • the temperature used in each method step does not exceed 85°C.
  • the recycling rate is at least 70%, and up to 80%.
  • the solvents used may be recovered in analytical quality.
  • the nitrogen introducing aromatic amine which is used during the diazotation step can be recovered in rates up to 90%.
  • cosmetically acceptable salts are preferred.
  • Preferred cosmetically acceptable salts are the lithium, sodium, potassium, ammonium, magnesium and calcium salts of 2- methoxymethyl-p-phenylenediamine (I), or of intermediates discussed herein, respectively.
  • the term salt, as used herein, comprises salts in the classical meaning, as well as addition salts. Addition salts encompass addition complexes with acid, base and/or solvent(s).
  • addition salts with an acid include complexes of the target compound or of intermediates disclosed herein, with hydrogen chloride, hydrogen bromide, sulfuric acid, phosphoric acid, acetic add, citric acid, succinic acid, tartaric acid, lactic acid, tosylic acid, benzenesulfonic acid.
  • addition salts with a base include complexes of the target compound or of intermediates disclosed herein, with a base such as sodium hydroxide, potassium hydroxide, ammonia, amines or alkanolamines.
  • solvates examples include complexes of the target compound or of intermediates disclosed herein with water (hydrates) or lower alcohols, i.e, methanol, ethanol, isopropanol, n- propanol, isobutanol, n-butanol.
  • Preferred solvates are hydrates.
  • steps described to prepare 2-methoxymethyt-p-phenylenediamine according to formula (I) may be performed in a sequential one-pot synthesis, with reagents added to a reactor one at a time and without excessive work-up in between besides.
  • the reaction steps require suitable solvents, as indicated below. Sequential one-pot synthesis without work-up inbetween is preferred unless it is preferred to avoid by-products from a preceding step in a subsequent step.
  • the present invention relates to a telescoping process for the preparation of 2-methoxymethyl-p- phenylenediamine (I), a salt thereof, for example a cosmetically acceptable salt thereof, or mixture thereof, comprising the steps as described in the following.
  • 2-nitrobenzylalcohol (II) is suspended with Benzyl-tributyl-ammonium chloride as phase transfer catalyst in toluene to form a homogeneous, brownish suspension.
  • Addition of sodium hydroxide and further amounts of toluene followed by addition of dimethyl sulfate started the methylation reaction.
  • After stirring for 4 h at 20°C the reaction is complete and accordingly quenched with 25% aqueous ammonia solution and allowed to be left overnight to completely decompose any traces of dimethyl sulfate.
  • the desired 2-methoxymethyl-nitrobenzene (III) is isolated via extraction with brine from the toluene fraction as brownish oil with low viscosity in 95% yield.
  • the separated toluene is recovered via mild vacuum distillation and could be recycled up to a rate of 80%.
  • the oily 2-methoxymethyl-nitrobenzene (III) is dissolved in an excess of methanol while Pd/C (moisturized with 50% water) is added to the mixture and the vessel purged with nitrogen prior to the addition of hydrogen.
  • the hydrogenation step is principally carried out in the presence of a hydrogen source.
  • the hydrogen source may be selected from ammonium formate, hydrazine or H 2 with a metal catalyst selected from the group consisting of Fe, Pd/C, Pd/(OH) 2 , Raney-Ni, Pt/C, PtOj and mixtures thereof.
  • the hydrogen source may be Hi, and the metal catalyst may be a Pd/C catalyst.
  • the solvent(s) used in this step may be selected from the group consisting of 1,2 -di methoxy ethane, pentane, cyclopentane, hexane, cyclohexane, benzene, toluene, methylacetate, ethylacetate, n- propylacetate, iso-propylacetate, n-butylacetate, methylpropionate, ethylpropionate, n- propylpropionate, iso-propylpropionate, n-buty I propionate, 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl-tetrahydrofuran, n-butanol, isopropanol, n-propanol, ethanol, methanol, water and mixtures thereof.
  • the solvent may be selected from the group consisting of methanol, ethanol, ethyl acetate, toluene and mixtures thereof.
  • the solvent may preferably be selected from methanol, ethanol and/or ethyl acetate, or an aqueous solution of methanol and/or ethanol.
  • o-toluidine (II)* can be carried out following a known: industrial procedure (e.g. CN 111808075) while reacting o-toluidine (II)* and chlorine gas in dichloroethane in the presence of a radical starter such as AIBN.
  • a radical starter such as AIBN.
  • other common radical starters such as dibenzoyl peroxide can be used.
  • the intermediate 2-amino-benzylchloride (II)** is isolated in yields >90%.
  • the subsequent methylation using sodium methanolate in methanol runs smoothly to deliver the expected 2-methoxy-methyl- aniline (IV) in good to excellent yields.
  • the hydrogenation step is principally carried out in the presence of a hydrogen source.
  • the hydrogen source may be selected from ammonium formate, hydrazine or H 2 with a metal catalyst selected from the group consisting of Fe, Pd/C, Pd/(OH) 2 , Raney-Ni, Pt/C, PtO 2 and mixtures thereof.
  • the hydrogen source may be H 2
  • the metal catalyst may be a Pd/C catalyst.
  • the solvent(s) used in this step may be selected from the group consisting of 1,2-di methoxyethane, pentane, cyclopentane, hexane, cyclohexane, benzene, toluene, methylacetate, ethylacetate, n- propylacetate, iso-propylacetate, n-butylacetate, methylpropionate, ethylpropionate, n- propylpropionate, iso-propylpropionate, n-buty I propionate, 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl-tetrahydrofuran, n-butanol, isopropanol, n-propanol, ethanol, methanol, water and mixtures thereof.
  • the solvent may be selected from the group consisting of methanol, ethanol, ethyl acetate, toluene and mixtures thereof
  • the solvent may preferably be selected from methanol, ethanol and/or ethyl acetate, or an aqueous solution of methanol and/or ethanol.
  • the solvent(s) used for the methylation may be selected from: the group consisting of methanol, ethanol, isopropyl alcohol, sulfuric acid, DMF, Chloroform:, 1,2-dimethoxyethane, pentane, cyclopentane, hexane, cyclohexane, benzene, toluene, 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl-tetrahydrofuran and mixtures thereof.
  • the solvent(s) are selected from methanol and sulfuric acid and mixtures thereof and aqueous solutions thereof.
  • the diazotation step is carried out in the presence of at least one nitrosation agent.
  • the nitrosation agent(s) may be selected from the group consisting of sodium nitrite, potassium nitrite, dinitrogen pentoxide, nitrosyl sulfuric acid and mixtures thereof.
  • the mineral or organic acid may be selected from the group consisting of hydrogen chloride, trifluoroacetic acid, sulfuric acid, sutfurous acid, carbonic acid, nitric acid, acetic acid, propionic acid, phosphoric acid and mixtures thereof.
  • the mineral or organic acid may be selected from the group consisting of hydrogen chloride, sulfuric acid, sulfurous acid, acetic acid and mixtures thereof.
  • the mineral or organic acid may be sulfuric acid.
  • the solvent(s) used in this step may be selected from the group consisting of 1,2-dimethoxy-ethane, pentane, cyclopentane, hexane, cyclohexane, benzene, toluene, 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl-tetrahydrofuran, n-pentanol, n-butanol, acetic acid, propionic acid, oxalic acid, malonic acid, sulfuric acid, phosphoric acid, iso-pentanol, t-butanol, isopropanol, n-propanol, ethanol, methanol, glycols, hydrogen chloride, water and mixtures thereof.
  • the solvent(s) may be selected from the group consisting of n-butanol, isopropanol, n- propanol, ethanol, methanol, acetic acid, propionic acid, oxalic acid, malonic acid, hydrogen chloride, sulfuric acid, phosphoric acid and mixtures thereof.
  • the solvent(s) may be selected from the group consisting of n-propanol, acetic acid, propionic acid, oxalic acid, malonic acid, hydrogen chloride, sulfuric acid, phosphoric acid, water and mixtures thereof.
  • the disodium;4-((E)-[3-(methoxymethyl)-4-(sulfonatomethylamino)phenyl]azo]-benzenesulfonate (X) is suspended in isopropyl alcohol to form a homogeneous suspension followed by the excessive addition of 32% sodium hydroxide solution as a strong base. This mixture is then heated to reflux for 2h at 80°C. After 1.5h the formation of a reddish precipitate started while the heating was stopped after 2h.
  • the base may be selected from sodium hydroxide, potassium hydroxide, calcium carbonate, sodium carbonate, potassium carbonate, sodium acetate, DBU, DBN, Huenig Base, ammonium sulfate, sodium hydrogencarbonate and potassium hydrogencarbonate.
  • sodium hydroxide and potassium hydroxide are used as the base.
  • Acids for the neutralization step used herein can be selected from the group of at least one mineral or organic acid.
  • the mineral or organic acid may be selected from the group consisting of hydrogen chloride, trifluoroacetic acid, sulfuric acid, sulfurous acid, carbonic acid, nitric acid, acetic acid, propionic acid, phosphoric acid and mixtures thereof.
  • Preferred mineral or organic acids are hydrogen chloride, sulfuric acid, sulfurous acid, acetic acid and mixtures thereof.
  • the mineral or organic acid may be hydrochloric acid or sulfuric acid.
  • the sulfanilic acid (IX) is separated from the charcoal and the palladium catalyst via pH adjustments.
  • the filtered material mixture is treated with aqueous 32% sodium hydroxide solution.
  • the sulfonic acid containing materials e.g. sulfanilic acid (IX)
  • the sulfonic acid containing materials are converted to the corresponding sodium salts and are dissolved easily in the aqueous phase whilst the charcoal and the palladium catalyst can be filtered off, separated and reused for another chemical operation.
  • the catalyst can be reused at least for 10 consecutive chemical operations, such as hydrogenations as described herein.
  • the aqueous phase in then acidified with hydrochloric acid.
  • the sulfanilic acid (IX) After cooling down to 0-5’C, the sulfanilic acid (IX) is precipitated and can be easily collected by filtration. The maximum recovery rate was observed to be ca. 80%.
  • the isolated sulfanilic acid (IX) can be again used for chemical operations such as diazotation as described herein to drive economics of the chemical process described herein.
  • the toluene solution is then slowly cooled down to 0-5 °C whilst the crystallization of 2-methoxymethyl-p-phenylenediamine (I) started already at 30°C. After 30 min., the precipitation is complete and the crystals are collected in 90% yield by filtration, washed with small portions of toluene and air dried in vacuum at 60°C for 3-5h. Also, the toluene filtrate is recovered successfully up to a rate of 95% via evaporation under vacuum. The 2-methoxymethyl-p- phenylenediamine (I) is obtained at this stage already in cosmetically acceptable purity according to global regulations.
  • the azo cleaving step is principally carried out in the presence of a hydrogen source.
  • the hydrogen source may be selected from ammonium formate, hydrazine or H 2 with a metal catalyst selected from the group consisting of Fe, Pd/C, Pd/(OHh, Raney-Ni, Pt/C, PtCh and mixtures thereof.
  • the hydrogen source may be Hj with a Pd/C catalyst.
  • the solvent(s) used in this step may be selected from the group consisting of 1,2-dimethoxyethane, pentane, cyclopentane, hexane, cyclohexane, benzene, toluene, methylacetate, ethylacetate, n-propylacetate, iso-propylacetate, n- butylacetate, methyl propionate, ethyl propionate, n-propy I propionate, iso-propyl propionate, n- butylpropionate, 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl-tetrahydrofuran, n-butanol, isopropanol, n-propanol, ethanol, methanol, water and mixtures thereof.
  • the solvent may be selected from the group consisting of methanol, ethanol, water, ethyl acetate, toluene and mixtures thereof.
  • the solvent may preferably be selected from methyl acetate, methanol, ethanol and/or ethyl acetate, or an aqueous solution thereof.
  • the amine source of compounds of the general formula NH2-R1 (VI ⁇ comprises a primary amine group.
  • the moiety R1 may be selected from:
  • R2 representing a phenyl group bearing a sulfonic acid group selected at any position at the benzene ring
  • R3 representing a naphthalene group bearing a sulfonic acid group selected at any position at the naphthalene ring system
  • R7 represents a chloro-benzene group whereas the chloro atom can be selected at any position at the benzene ring
  • R8 represents a bromo-benzene group whereas the bromo atom can be selected at any position at the benzene ring
  • R9 represents a fluor-benzene group whereas the fluor atom can be selected at any position at the benzene ring
  • RIO represents a phenyl group bearing one or more carboxyl acid groups , in particular one or two carboxyl acid groups selected at any position at the benzene ring
  • Rll represents a phenyl group bearing a nitro group selected at any position at the benzene ring
  • R12 represents a 1-methyl-imidazole group whereas the conjunction to the amino group in NH2- R1 (VI) may occur at any of the free carbon positions of the 1-methyl-imidazole ring
  • R13 represents thiazole group whereas the conjunction to the amino group in NH2-R1 (VI) may occur at any of the free carbon positions of the thiazole ring
  • R14 represents a naphthalene group bearing 2 sulfonic acid group selected at any position at the naphthalene ring system
  • R15 represents a naphthalene group bearing 2 sulfonic acid mixed metal (sodium and potassium) salt groups selected at any position at the naphthalene ring system:
  • the phase transfer catalyst may be selected from quaternary nitrogen compounds comprising alkyl trimethyl ammonium salts, quaternized esters, dialkyl dimethyl ammonium salts, benzalkonium salts, crown ether derivatives such as 18-crown-6, 15-crown-5 and 12-crown ⁇ 4, imidazolium salts and pyridinium salts.
  • a preferred compound is benzyl-tributyl-ammonium chloride.
  • Bases described in the process may be selected from sodium hydroxide, potassium hydroxide, calcium carbonate, sodium carbonate, potassium carbonate, sodium acetate, DBU, DBN, Huenig
  • Base ammonium sulfate, sodium hydrogen carbonate and potassium hydrogen carbonate.
  • sodium hydroxide is the preferred base.
  • Solvents used for any preparation methods and crystallization methods as described generally may be selected from the group of water, 1,2-dimethoxyethane, ethyl acetate, methyl acetate, pentane, cyclopentane, hexane, cyclohexane, benzene, toluene, 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl-tetrahydrofuran, n-pentanol, n-butanol, acetic acid, propionic acid, oxalic acid, malonic acid, sulfuric acid, phosphoric acid, iso-pentanol, t-butanol, isopropanol, n-propanol, ethanol, methanol, glycols, hydrogen chloride, water and mixtures thereof.
  • the solvent for the crystallization may be selected from the group consisting of water, toluene, ethyl acetate, methyl acetate, isopropanol, n-propanol, ethanol, methanol, and mixtures thereof.
  • the hydrogenation step is principally carried out in the presence of a hydrogen source.
  • the hydrogen source may be selected from electrochemical methods such as reductive electrolysis in aquous/alcoholic solutions, ammonium formate, hydrazine or hydrogen with a metal catalyst selected from the group consisting of Fe, Pd/C, Pd/(OH) 2 , Raney-Ni, Pt/C, PtO 2 and mixtures thereof.
  • the hydrogen source may be electricity (electrical current), hydrogen or ammonium formate
  • the metal catalyst may be a Pd/C catalyst.
  • the solvent(s) used in this step may be selected from the group consisting of 1,2-dimethoxyethane, pentane, cyclopentane, hexane, cyclohexane, benzene, toluene, methyl acetate, ethyl acetate, n-propyl acetate, iso-propyl acetate, n-butyl acetate, methyl propionate, ethyl propionate, n-propyl propionate, iso-propyl propionate, n- butyl propionate, 1,4-dioxane, diethyl ether, tetra hydrofuran, methyl-tetrahydrofuran, n-butanol, isopropanol, n-propanol, ethanol, methanol, water and mixtures thereof.
  • the solvent may be selected from the group consisting of methanol, ethanol, methyl acetate, ethyl acetate, toluene and mixtures thereof.
  • the solvent may preferably be selected from methanol, ethanol and/or methyl acetate and/or ethyl acetate, or an aqueous solution of methanol and/or ethanol.
  • the hydrogen source may be selected from electricity (electrical current), ammonium formate, hydrazine or hydrogen with a metal catalyst selected from the group consisting of Fe, Pd/C, Pd/(OH)2, Raney-Ni, Pt/C, PtO2 and mixtures thereof.
  • the hydrogen source may be ammonium formate and hydrogen with a Pd/C catalyst.
  • the solvent(s) used in this step may be selected from the group consisting of 1,2-dimethoxyethane, pentane, cyclopentane, hexane, cyclohexane, benzene, toluene, methyl acetate, ethyl acetate, n-propyl acetate, iso-propyl acetate, n-butyl acetate, methyl propionate, ethyl propionate, n-propyl propionate, iso-propyl propionate, n- butyl propionate, 1,4-dioxane, diethyl ether, tetra hydrofuran, methyl-tetrahydrofuran, n-butanol, isopropanol, n-propanol, ethanol, methanol, water and mixtures thereof.
  • the solvent may be selected from the group consisting of methanol, ethanol, water, methyl acetate, ethyl acetate, toluene and mixtures thereof.
  • the solvent may preferably be selected from methanol, ethanol and/or ethyl acetate, and/or methyl acetate or an aqueous solution thereof.
  • 500 ml methanol are prepared in a 3 necked glass flask and 2 eq. of cone, sulfuric acid are added slowly and heated to 50 °C.
  • 50 g (1 eq.) 2-amino-benzyl alcohol (II )• ** are dissolved in 500 ml methanol and this solution is added over 30 min whilst the temperature is maintained at 50°C.
  • the reaction mixture is further stirred for 5 h and allowed to cool down to RT. Then, small portions of water and a solution of sodium hydroxide are added to keep the pH>8.
  • the reaction mixture was allowed to cool to 70 °C as is filtered off.
  • the precipitate is washed with 0.5 parts by volume of iso-propanol.
  • the collected solid is suspended in 1.0 eq. of iso-propanol to forma dark reddish solution.
  • 2.1 eq. of a hydrochloric acid (25%) solution is added over 15 min whilst a dark reddish precipitate is formed.
  • the reaction mixture is filtered off and the precipitate is washed 3 times with 1 eq. of iso-propanol.
  • the product 4- [(E)-[4-amino-3-(methoxymethyl)-phenyl]azo]-benzenesulfonic acid (XI) is dried and obtained in 93% yield (1231 g).
  • the reaction mixture is filtered off and the residue comprising of the catalyst and sulfanilic acid (IX) is washed 3 times with 1 eq. of methyl acetate each.
  • the clear filtrate is evaporated to decrease the volume by 70% under reduced pressure (40X/200 mbar).
  • 4 eq. (4924 ml) of toluene are added to the methyl acetate solution when the remaining 30 vol% of methyl acetate are again evaporated under vacuum (40°C/100 mbar).
  • the remaining toluene solution is slowly cooled down to 0-5’C when the formation of crystals already starts at 30°C.
  • the reaction mixture is stirred for another 30 min.
  • step (IX) comprises
  • step (a2) reducing 2-methoxymethyl-nitrobenzene (III) to form 2-(methoxymethyl)aniline (IV),
  • step (a) comprises:
  • step (a) comprises: (a5) reducing o-nitro-benzyl alcohol (II) to form 2-amino-benzyl alcohol (II)***
  • step (b) comprises adding an aqueous solution of hydroxymethanesulfonate to a solution of 2- (methoxymethyl)aniline (IV) in methanol, ethanol, isopropanol, n-propanol, or a mixture thereof, or in an aqueous solution comprising at least 50 wt% methanol, ethanol, isopropanol, n-propanol, or a mixture thereof, in particular a solution of 2-(methoxymethyl)aniline (IV) in methanol.
  • step (b) further comprises separating [2-methoxymethyl-anilino]methane sulfonate (V).
  • step (c) comprises diazotizing aromatic amine (VI) in aqueous solution in the presence of a nitrosation agent under acidic conditions.
  • the nitrosation agent is selected from sodium nitrite, potassium nitrite, dinitrogen pentoxide, nitrosyl sulfuric acid and mixtures thereof.
  • step (c) further comprises separating 4-azo-2-methoxymethyl-(sulfomethyl)aniline (VII).
  • step (d) is carried out in alkaline medium.
  • step (dl) comprises adding an aqueous alkaline solution to a suspension of 4-azo-2-methoxymethyl- (sulfomethyl)aniline (VII) in methanol, ethanol, isopropanol, n-propanol, or a mixture thereof, or in an aqueous solution comprising at least 50 wt% methanol, ethanol, isopropanol, n- propanol, or a mixture thereof.
  • VI 4-azo-2-methoxymethyl- (sulfomethyl)aniline
  • step (dl) further comprises filtering off 4-azo-2-(methoxymethyl)aniline (VIII).
  • step (e) is carried out using a hydrogen source in the presence of metal catalyst, in particular using as the hydrogen source ammonium formate, hydrazine hydrate and/or H2.
  • step (e) is carried out using an electrochemical method.
  • the solvent used in step (e) is methanol, ethanol, isopropanol, methyl acetate, ethyl acetate, toluol or a mixture thereof.
  • step (f) comprises concentrating the solution by distilling-off solvent, and adding a non-polar organic solvent to precipitate 2- me t ho xym et hy I -p- p he ny I e ne d i a m i ne ( I ) .

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

L'invention concerne un procédé de préparation de 2-méthoxyméthyl-p-phénylènediamine.
PCT/EP2024/081428 2023-11-10 2024-11-07 Nouvelle synthèse télescopique hautement économique de 2-méthoxyméthyl-p-phénylènediamine Pending WO2025099119A1 (fr)

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Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030041392A1 (en) 1999-11-29 2003-03-06 Otto Goettel Process for making 1,4-diamino-2-methoxymethylbenzene and salts thereof and compositions and methods for dyeing keratin fibers containing same
WO2012044758A1 (fr) 2010-09-29 2012-04-05 The Procter & Gamble Company Procédés de synthèse de 2-méthoxyméthyl-1,4-benzènediamine
CN104744272A (zh) 2015-03-24 2015-07-01 浙江鼎龙科技有限公司 一种2-(甲氧基甲基)苯基-1,4-二胺的制备方法
EP3215482A1 (fr) 2014-11-04 2017-09-13 Noxell Corporation Procédé de préparation de 1,4-benzène diamines 2-substituées et sels de celles-ci
EP3215483A1 (fr) 2014-11-04 2017-09-13 Noxell Corporation Synthèse télescopique de 2-méthoxyméthyl-p-phénylènediamine
EP3215484A1 (fr) 2014-11-04 2017-09-13 Noxell Corporation Synthèse emboîtée de 2-méthoxyméthyl-p-phénylènediamine
CN111808075A (zh) 2020-09-07 2020-10-23 湖南速博生物技术有限公司 一种吡啶喹唑啉中间体的制备方法
WO2022090235A1 (fr) 2020-10-27 2022-05-05 Wella Germany Gmbh 2-méthoxyméthyl-p-phénylènediamine de qualité cosmétique
EP4013739A1 (fr) 2019-08-13 2022-06-22 Wella Germany GmbH Nouvelles synthèses télescopiques de 2-méthoxyméthyl-p-phénylènediamine

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030041392A1 (en) 1999-11-29 2003-03-06 Otto Goettel Process for making 1,4-diamino-2-methoxymethylbenzene and salts thereof and compositions and methods for dyeing keratin fibers containing same
WO2012044758A1 (fr) 2010-09-29 2012-04-05 The Procter & Gamble Company Procédés de synthèse de 2-méthoxyméthyl-1,4-benzènediamine
EP3215482A1 (fr) 2014-11-04 2017-09-13 Noxell Corporation Procédé de préparation de 1,4-benzène diamines 2-substituées et sels de celles-ci
EP3215483A1 (fr) 2014-11-04 2017-09-13 Noxell Corporation Synthèse télescopique de 2-méthoxyméthyl-p-phénylènediamine
EP3215484A1 (fr) 2014-11-04 2017-09-13 Noxell Corporation Synthèse emboîtée de 2-méthoxyméthyl-p-phénylènediamine
CN104744272A (zh) 2015-03-24 2015-07-01 浙江鼎龙科技有限公司 一种2-(甲氧基甲基)苯基-1,4-二胺的制备方法
EP4013739A1 (fr) 2019-08-13 2022-06-22 Wella Germany GmbH Nouvelles synthèses télescopiques de 2-méthoxyméthyl-p-phénylènediamine
CN111808075A (zh) 2020-09-07 2020-10-23 湖南速博生物技术有限公司 一种吡啶喹唑啉中间体的制备方法
WO2022090235A1 (fr) 2020-10-27 2022-05-05 Wella Germany Gmbh 2-méthoxyméthyl-p-phénylènediamine de qualité cosmétique

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