Granted Patent B2

US 9,688,609 · App. 14/926,163 · Granted Jun 27, 2017

Abstract

Claims (24)

1. A telescoping process for the preparation of 2-methoxymethyl-p-phenylenediamine (I), a cosmetically acceptable salt thereof, or mixture thereof comprising the steps of:

a) synthesizing the intermediate 2-(hydroxymethyl)-4-{3-[2-(hydroxymethyl)phenyl]triaz-1-en-1-yl}aniline (IV) via diazotation using 2-hydroxymethylaniline (II) to obtain the intermediate of formula (III) followed by diazo coupling between the intermediate of formula (III) and 2-hydroxymethylaniline (II):

b) synthesizing the intermediate 2-(hydroxymethyl)-4-{(E)-[2-(hydroxymethyl)phenyl]diazenyl}aniline of formula (V) via rearrangement of the intermediate 2-(hydroxymethyl)-4-{3-[2-(hydroxymethyl)phenyl]triaz-1-en-1-yl}aniline (IV) obtained in step a):

c) synthesizing 2-hydroxymethyl-p-phenylenediamine (VI) and 2-hydroxymethylaniline (II) via hydrogenation of the compound of formula (V):

d) synthesizing 2-methoxymethyl-p-phenylenediamine (I) via acid catalysed etherification of the compound of formula (VI):

2. The process according to claim 1 , wherein the process further comprises the step of converting 2-methoxymethyl-p-phenylenediamine (I) into a cosmetically acceptable salt.

3. The process according to claim 2 , wherein the cosmetically acceptable salt is selected from chloride, sulfate, hydrogensulfate or malonate salt.

4. The process according to claim 1 , wherein step a) is carried out in the presence of at least one nitrosation agent.

5. The process according to claim 4 , wherein the nitrosation agent is selected from the group consisting of sodium nitrite, potassium nitrite, dinitrogen pentoxide, nitrosylsulfuric acid and mixtures thereof.

6. The process according to claim 1 , wherein step a) is carried out in the presence of at least one radical scavenger.

7. The process according to claim 1 , wherein step a) or b) is carried out in the presence of at least one mineral or organic acid.

8. The process according to claim 7 , wherein the mineral or organic acid is 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.

9. The process according to claim 7 , wherein the mineral or organic acid is selected from the group consisting of hydrogen chloride, sulfuric acid, sulfurous acid, acetic acid and mixtures thereof.

10. The process according to claim 1 , wherein the solvent used in step a) or b) is selected from the group consisting of 1,2-dimethoxyethane, 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, sulphuric acid, phosphoric acid, iso-pentanol, t-butanol, isopropanol, n-propanol, ethanol, methanol, glycols, hydrogen chloride, water and mixtures thereof.

11. The process according to claim 1 , wherein step c) carried out in the presence of a hydrogen source selected from 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.

12. The process according to claim 1 , wherein step c) is carried out in the presence of H 2 with a Pd/C catalyst.

13. The process according to claim 1 , wherein the solvent used in step c) is selected from the group consisting of 1,2-dimethoxyethane, pentane, cyclopentane, hexane, cyclohexane, benzene, toluene, methylacetate, ethylacetate, n-propylacetate, iso-propylacetate, n-butylacetate, methylpropionate, ethylpropionate, n-propylpropionate, iso-propylpropionate, n-butylpropionate, 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl-tetrahydrofuran, n-butanol, isopropanol, n-propanol, ethanol, methanol, water and mixtures thereof.

14. The process according to claim 1 , wherein the solvent used in step c) is selected from the group consisting of methanol, ethanol, ethylacetate, toluene and mixtures thereof.

15. The process according to claim 1 , wherein the acid used in step d) is selected from the group consisting of hydrogen chloride, hydrogen bromide, sulphuric acid, phosphoric acid, acetic acid, trifluoro acetic acid and mixtures thereof.

16. The process according to claim 1 , wherein the solvent used in step d) is selected from the group consisting of 1,2-dimethoxyethane, pentane, cyclopentane, hexane, cyclohexane, benzene, toluene, 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl-tetrahydrofuran, n-pentanol, iso-pentanol, t-butanol, isopropanol, n-propanol, ethanol, methanol, water, glycols and mixtures thereof.

17. The process according to claim 1 , wherein the methylating agent used in step d) is methanol.

18. The process according to claim 1 , wherein 2-hydroxymethyl-aniline (II) is prepared via hydrogenation of 2-nitro-benzyl alcohol (VII):

19. The process according to claim 18 , wherein the hydrogenation of 2-nitro-benzyl alcohol (VII) is carried out in the presence of a hydrogen source selected from 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.

20. The process according to claim 18 , wherein the solvent used for the hydrogenation of 2-nitro-benzyl alcohol (VII) is selected from the group consisting of 1,2-dimethoxyethane, pentane, cyclopentane, hexane, cyclohexane, benzene, toluene, methylacetate, ethylacetate, n-propylacetate, iso-propylacetate, n-butylacetate, methylpropionate, ethylpropionate, n-propylpropionate, iso-propylpropionate, n-butylpropionate, 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl-tetrahydrofuran, n-butanol, isopropanol, n-propanol, ethanol, methanol, water and mixtures thereof.

Assignments (8)