Process for the preparation of 2,2,6,6-tetramethyl-4-piperidyl-amines

Abstract: A process for the preparation of 2,2,6,6-tetramethyl-4-piperidylamine of the formula (I) in which n is 1, 2 or 3 and, if n is 1, R is C₁-C₁₈-alkyl, C₅-C₁₂-cyclo­ alkyl, C₇-C₉-phenylalkyl, tetrahydrofurfuryl, C₂-C₄-alkyl which is monosubstituted by OH, C₁-C₈-alkyloxy, C₁-C₈-alkylamino, cyclohexylamino or di(C₁-C₈-alkyl)amino, or C₂-C₆-alkyl which is substituted by an -NH₂ group, or R is 2,2,6,6-tetramethyl-4-piperidyl, and, if n is 2, R is C₂-C₁₂-alkylene, cyclohexylene, methylenedicyclohexylene, cyclohexylene­ dimethylene, xylylene or C₄-C₁₂-alkylene which is interrupted by 1, 2 or 3 oxygen atoms or 1 or 2 NH or N-CH₃ groups, and, if n is 3, R is a group of the formula (II) in which x and y are identical or different and are integers from 2 to 6 and z is zero or 1, characterized in that 2,2,6,6-tetramethyl-4-­ piperidone is reacted with an amine of the formula (III) R-(NH₂) n (III) in which R and n are as defined above, in the presence of hydrogen and of a hydrogenation catalyst, unsupported or supported on an inert material, in the absence of a solvent or in the presence of a quantity of water less than 10 % by weight relative to the reaction mixture.

Description: The present invention relates to a novel and convenient process for the preparation of 2,2,6,6-tetramethyl-4-piperidylamines, which is based on the reductive amination of 2,2,6,6-tetramethyl-4-piperidone in the presence of platinum or palladium as hydrogenation catalyst, in the absence of a solvent or in the presence of a quantity of water less than 5 % by weight relative to the reaction mixture. 2,2,6,6-Tetramethyl-4-piperidylamines are compounds of considerable industrial interest, since they can be used for the preparation of light stabilizers for synthetic polymers. Their preparation has therefore been extensively described in the patent literature; this involves the reductive amination of 2,2,6,6-tetramethyl-4-piperidone in an organic solvent or in water or in a water/alcohol mixture, in the presence of a hydrogenation catalyst such as platinum, palladium or nickel. In particular, US Patents 3,904,581, 4,104,248, 4,315,859, 4,326,063, 4,415,688 and 4,533,688, German Patent 3,007,996 and WO 81/1,706 describe the preparation of 2,2,6,6-tetramethyl-4-piperidylamines, using methanol as the reaction medium; in US Patents 4,605,743 and 4,607,104, the reaction is carried out in water or in water/alcohol mixtures. The present invention relates to a process for the preparation of 2,2,6,6-tetramethyl-4-piperidylamines of the general formula (I) in which n is 1, 2 or 3 and, if n is 1, R is C₁-C₁₈-alkyl, C₅-C₁₂-cycloalkyl, C₇-C₉-phenylalkyl, tetrahydrofurfuryl, C₂-C₄-alkyl which is monosubstituted by OH, C₁-C₈-alkyloxy, C₁-C₈-alkylamino, cyclohexylamino or di(C₁-C₈-alkyl)amino, or C₂-C₆-alkyl which is substituted by an -NH₂ group, or R is 2,2,6,6-tetramethyl-4-piperidyl, and, if n is 2, R is C₂-C₁₂-alkylene, cyclohexylene, methylenedicyclohexylene, cyclohexylenedimethylene, xylylene or C₄-C₁₂-alkylene which is interrupted by 1, 2 or 3 oxygen atoms or 1 or 2 NH or N-CH₃ groups, and, if n is 3, R is a group of the formula (II) in which x and y are identical or different and are integers from 2 to 6 and z is zero or 1, characterized in that 2,2,6,6-tetramethyl-4-piperidone is reacted with an amine of the formula (III) R-(NH₂) n (III) in which R and n are as defined above, in the presence of hydrogen and of platinum or palladium as hydrogenation catalyst, unsupported or supported on an inert material, in the absence of a solvent or in the presence of a quantity of water less than 5 % by weight relative to the reaction mixture. The advantages of the procedure according to the present invention are clearly evident: a) the absence of inflammable solvents, apart from representing an economic advantage, eliminates the fire risk connected with the use of pyrophoric catalysts, and b) the absence of a solvent permits a significant increase in productive capacity per unit of reactor volume. Representative examples of C₁-C₁₈-alkyl R are: methyl, ethyl, propyl, isopropyl, butyl, 2-butyl, isobutyl, t-butyl, pentyl, hexyl, octyl, 2-ethylhexyl, 1,1,3,3-tetramethylbutyl, nonyl, decyl, undecyl, dodecyl, tetradecyl, hexadecyl and octadecyl. C₁-C₈-alkyl is preferred. Representative examples of C₅-C₁₂-cycloalkyl R are: cyclopentyl, cyclohexyl, methylcyclohexyl, dimethylcyclohexyl, trimethylcyclohexyl, cyclooctyl and cyclododecyl. A cycloalkyl group of the formula with a being an integer from 4 to 7 is preferred. Said group may optionally be substituted by C₁-C₄-alkyl, in particular methyl. Cyclohexyl is especially preferred. Representative examples of C₇-C₉-phenylalkyl R are: benzyl, methylbenzyl, dimethylbenzyl and 2-phenylethyl. Benzyl unsubstituted or substituted at the phenyl ring by methyl is preferred. Representative examples of C₂-C₄-alkyl R which is monosubstituted by OH are: 2-hydroxyethyl, 2-hydroxypropyl, 3-hydroxypropyl, 2-hydroxybutyl and 4-hydroxybutyl. 2-Hydroxyethyl is preferred. Representative examples of C₂-C₄-alkyl R which is monosubstituted by C₁-C₈-alkyloxy are: 2-methoxyethyl, 2-ethoxyethyl, 2-butoxyethyl, 3-methoxypropyl, 3-ethoxypropyl, 3-propoxypropyl, 3-butoxypropyl, 3-hexyloxypropyl and 3-octyloxypropyl. 3-Methoxypropyl is preferred. Representative examples of C₂-C₄-alkyl R which is monosubstituted by C₁-C₈-alkylamino or cyclohexylamino are: 2-methylaminoethyl, 3-methylaminopropyl, 3-ethylaminopropyl, 3-butylaminopropyl, 3-hexylaminopropyl, 3-octylaminopropyl and 3-cyclohexylaminopropyl. Representative examples of C₂-C₄-alkyl R which is monosubstituted by di(C₁-C₈-alkyl)amino are: 2-dimethylaminoethyl, 3-dimethylaminopropyl, 3-diethylaminopropyl, 3-dibutylaminopropyl, 3-dihexylaminopropyl and 3-dioctylaminopropyl. 3-Dimethylaminopropyl and 3-diethylaminopropyl are preferred. Representative examples of C₂-C₆-alkyl R which is substituted by an -NH₂ group are: 2-aminoethyl, 2-aminopropyl, 3-aminopropyl, 4-aminobutyl, 5-aminopentyl, 6-aminohexyl and 3-amino-2,2-dimethylpropyl. 2-Aminoethyl is preferred. Representative examples of C₂-C₁₂-alkylene R are: ethylene, propylene, trimethylene, tetramethylene, pentamethylene, 2,2-dimethyltrimethylene, hexamethylene, octamethylene, decamethylene and dodecamethylene. C₂-C₆-alkylene is preferred. Representative examples of C₄-C₁₂-alkylene R which is interrupted by 1, 2 or 3 oxygen atoms are: 3-oxapentane-1,5-diyl, 4-oxaheptane-1,7-diyl, 3,6-dioxaoctane-1,8-diyl, 4,9-dioxadodecane-1,12-diyl and 4,7,10-trioxatridecane-1,13-diyl. Representative examples of C₄-C₁₂-alkylene R which is interrupted by 1 or 2 NH or N-CH₃ groups are: 3-azapentane-1,5-diyl, 3-azahexane-1,6-diyl, 4-azaheptane-1,7-diyl, 7-azatridecane-1,13-diyl, 4,7-diazadecane-1,10-diyl and 4-methyl-4-azaheptane-1,7-diyl. Representative examples of a group R of the formula (II) are: The process according to the present invention is conveniently carried out by reacting 2,2,6,6-tetramethyl-4-piperidone with an amine of the formula (III) in the presence of hydrogen and of platinum or palladium without an addition of solvents. The amine of the formula (III) is preferably an anhydrous amine, for example anhydrous butylamine. In some cases a small quantity of water may be present, which originates e.g. from those amines of the formula (III) which are commercially available as concentrated aqueous solutions, in particular ethylamine containing 30 % of water and hexamethylenediamine containing 15 % of water. The water present in the mixture of the reagents is in any case less than 5 % relative to the weight of the said reagents. The ratio of the 2,2,6,6-tetramethyl-4-piperidone and the amine of the formula (III) can be the theoretical ratio, or it is possible to use an excess of piperidone up to 20 % of theory, when n is 2 or 3, but, if n is 1, it is preferable to use an excess of amine up to 20 % of theory. The catalysts which are used according to the process of the present invention are platinum or palladium, preferably platinum. The said catalysts can be used unsupported or supported on suitable inert materials, for example carbon, calcium carbonate, alumina and the like. The reductive amination is conveniently carried out at a temperature of 20° to 120°C, preferably 40° to 100°C, under a hydrogen pressure of 1 to 100 bar, preferably 10 to 80 bar. The process according to the present invention is possible because of the low melting point of 2,2,6,6-tetramethyl-4-piperidone (35°C) and the fact that the amines used as reagents for the reductive amination, and also the piperidylamines obtained, are usually liquid at room temperature or low-melting. For these reasons, it is possible to react molten 2,2,6,6-tetramethyl-4-piperidone with the amine in liquid or solid form without any difficulties; once the reductive amination is complete, the catalyst can be separated off directly or after dilution with water. Finally, the piperidylamines can be isolated by the usual procedures, for example by distillation or crystallization. In general, the process according to the present invention can be carried out by introducing the molten 2,2,6,6-tetramethyl-4-piperidone into an autoclave in such a way that the initial temperature in the reactor is between 40° and 50°C. Then, the amine may be slowly added in liquid or solid form, or, in the case of methylamine, in gaseous form. The amine introduced is preferably at an initial temperature between 0° and 60°C, in particular between 20° and 40°C. During the addition of the amine, the reaction mixture is conveniently cooled, in order not to exceed 60°C. After the addition of the amine, the catalyst can be introduced, preferably moistened with or suspended in water. The content of water added to the reaction mixture together with the catalyst is in general less than 2 % relative to the weight of the final reaction mixture. The reactor may be flushed several times with nitrogen and then pressurized with hydrogen and heated. When the absorption ceases, the reactor may be cooled to a temperature of 30-80°C, depending on the type of piperidylamine produced. The catalyst can be removed by filtration and the volatile products can be removed by distillation. Finally, the piperidylamine may be separated off by distillation or, when solid, crystallized, or used directly. Those amines of the formula (III) are preferred, in which n is 1 or 2 and, if n is 1, R is C₁-C₁₂-alkyl, C₅-C₉-cycloalkyl, benzyl, tetrahydrofurfuryl, C₂-C₃-alkyl which is monosubstituted by OH, C₁-C₄-alkyloxy, C₁-C₄-alkylamino, cyclohexylamino or di(C₁-C₄-alkyl)amino, or C₂-C₆-alkyl which is substituted by an -NH₂ group, or R is 2,2,6,6-tetramethyl-4-piperidyl, and, if n is 2, R is C₂-C₆-alkylene, cyclohexylene, methylenedicyclohexylene, cyclohexylenedimethylene or C₄-C₁₀-alkylene which is interrupted by 1 or 2 oxygen atoms or NH groups. Those amines of the formula (III) are particularly preferred, in which n is 1 or 2 and, if n is 1, R is C₁-C₈-alkyl, cyclohexyl, tetrahydrofurfuryl, 2,2,6,6-tetramethyl-4-piperidyl or C₂-C₃-alkyl which is monosubstituted by C₁-C₄-alkyloxy or by di(C₁-C₄-alkyl)amino, and, if n is 2, R is C₂-C₆-alkylene or C₄-C₁₀-alkylene which is interrupted by 1 or 2 oxygen atoms or NH groups. Amines of the formula (III) of special interest are those, in which n is 1 or 2 and, if n is 1, R is C₁-C₈-alkyl, cyclohexyl, 2,2,6,6-tetramethyl-4-piperidyl, 3-methoxypropyl, 3-dimethylaminopropyl or 3-diethylaminopropyl, and, if n is 2, R is C₂-C₆-alkylene. Amines of the formula (III) of particular interest are those, in which n is 1 or 2 and, if n is 1, R is C₁-C₈-alkyl or 3-diethylaminopropyl and, if n is 2, R is -(CH₂)₂₋₆-. The amines of the formula (III), used according to the process of the present invention, are commercially available products or can be prepared by analogy to known processes. 2,2,6,6-Tetramethyl-4-piperidone can also be prepared by known processes, for example as described in US Patents 3,513,170, 3,959,295 and 4,536,581. To illustrate the present invention more clearly, several examples of the preparation of 2,2,6,6-tetramethyl-4-piperidylamines are shown below. Example 1: Preparation of 4-butylamino-2,2,6,6-tetramethylpiperidine 776.2 g (5 mol) of molten 2,2,6,6-tetramethyl-4-piperidone (temperature about 40°C) are introduced into a 2 litre autoclave and 402.3 g (5.5 mol) of butylamine are added with stirring, while maintaining the temperature at 30-40°C. 5 g of 5 % Pt on carbon, containing 50 % of water, are then added, and the hydrogenation is carried out at 70-80°C under a hydrogen pressure of 50 bar, until absorption ceases (4 hours). After cooling to ambient temperature, the catalyst is removed by filtration and the 4-butylamino-2,2,6,6-tetramethyl-piperidine is separated off by distillation. Boiling point: 154-156°C/66 mbar. Yield: 98 % relative to 2,2,6,6-tetramethyl-4-piperidone. Examples 2 to 8: Following the procedure described in Example 1, the following piperidylamines of the formula are prepared. Example 9: Preparation of N,N'-bis-(2,2,6,6-tetramethyl-4-piperidyl)-trimethylenediamine 1,017.7 g (6.3 mol) of molten 2,2,6,6-tetramethyl-4-piperidone (temperature about 40°C) are introduced into a 2 litre autoclave and 222.4 g (3 mol) of trimethylenediamine are added with stirring, while maintaining the temperature at about 40°C. 6 g of 5 % Pt on carbon, containing 50 % of water, are then added, and the hydrogenation is carried out at 80°C under a hydrogen pressure of 50 bar until absorption ceases (4-5 hours). The mixture is cooled to 60-70°C, the catalyst is separated off by filtration and the N,N'-bis-(2,2,6,6-tetramethyl-4-piperidyl)-trimethylenediamine is isolated by distillation. Boiling point: 171-173°C/0.7 mbar. Yield: 92 % relative to the 2,2,6,6-tetramethyl-4-piperidone. Example 10: Preparation of N,N'-bis-(2,2,6,6-tetramethyl-4-piperidyl)-ethylenediamine The product is obtained as described in the preceding example by hydrogenation at 50-60°C under a hydrogen pressure of 50 bar. Boiling point: 167-169°C/0.7 mbar. Yield: 90 % relative to the 2,2,6,6-tetramethyl-4-piperidone.

Claims: A process for the preparation of 2,2,6,6-tetramethyl-4-piperidylamine of the formula (I) in which n is 1, 2 or 3 and, if n is 1, R is C₁-C₁₈-alkyl, C₅-C₁₂-cyclo-alkyl, C₇-C₉-phenylalkyl, tetrahydrofurfuryl, C₂-C₄-alkyl which is monosubstituted by OH, C₁-C₈-alkyloxy, C₁-C₈-alkylamino, cyclohexylamino or di(C₁-C₈-alkyl)amino, or C₂-C₆-alkyl which is substituted by an -NH₂ group, or R is 2,2,6,6-tetramethyl-4-piperidyl, and, if n is 2, R is C₂-C₁₂-alkylene, cyclohexylene, methylenedicyclohexylene, cyclohexylenedimethylene, xylylene or C₄-C₁₂-alkylene which is interrupted by 1, 2 or 3 oxygen atoms or 1 or 2 NH or N-CH₃ groups, and, if n is 3, R is a group of the formula (II) in which x and y are identical or different and are integers from 2 to 6 and z is zero or 1, characterized in that 2,2,6,6-tetramethyl-4-piperidone is reacted with an amine of the formula (III) R-(NH₂) n (III) in which R and n are as defined above, in the presence of hydrogen and of platinum or palladium as hydrogenation catalyst, unsupported or supported on an inert material, in the absence of a solvent or in the presence of a quantity of water less than 5 % by weight relative to the reaction mixture. A process according to claim 1, wherein the reductive amination of 2,2,6,6-tetramethyl-4-piperidone is carried out in the absence of a solvent. A process according to claim 1, wherein the reductive amination of 2,2,6,6-tetramethyl-4-piperidone is carried out with an anhydrous amine of the formula (III). A process according to claim 1, wherein the reductive amination of 2,2,6,6-tetramethyl-4-piperidone is carried out in the presence of a quantity of water less than 5 % by weight relative to the reaction mixture. A process according to claim 1, wherein the reductive amination of 2,2,6,6-tetramethyl-4-piperidone is carried out with ethylamine containing 30 % of water. A process according to claim 1, wherein the reductive amination of 2,2,6,6-tetramethyl-4-piperidone is carried out with hexamethylenediamine containing 15 % of water. A process according to claim 1, wherein the reductive amination of 2,2,6,6-tetramethyl-4-piperidone is carried out in the presence of platinum as hydrogenation catalyst. A process according to claim 1, wherein the reductive amination of 2,2,6,6-tetramethyl-4-piperidone is carried out at a temperature of 20° to 120°C. A process according to claim 1, wherein the reductive amination of 2,2,6,6-tetramethyl-4-piperidone is carried out at a temperature of 40° to 100°C. A process according to claim 1, wherein the reductive amination of 2,2,6,6-tetramethyl-4-piperidone is carried out under a hydrogen pressure of 1 to 100 bar. A process according to claim 1, wherein the reductive amination of 2,2,6,6-tetramethyl-4-piperidone is carried out under a hydrogen pressure of 10 to 80 bar. A process according to claim 1, wherein the reductive amination of 2,2,6,6-tetramethyl-4-piperidone is carried out by using an amine of the formula (III) in which n is 1 or 2 and, if n is 1, R is C₁-C₁₂-alkyl, C₅-C₉-cycloalkyl, benzyl, tetrahydrofurfuryl, C₂-C₃-alkyl which is monosubstituted by OH, C₁-C₄-alkyloxy, C₁-C₄-alkylamino, cyclohexylamino or di(C₁-C₄-alkyl)amino, or C₂-C₆-alkyl which is substituted by an -NH₂ group, or R is 2,2,6,6-tetramethyl-4-piperidyl, and, if n is 2, R is C₂-C₆-alkylene, cyclohexylene, methylenedicyclohexylene, cyclohexylenedimethylene or C₄-C₁₀-alkylene which is interrupted by 1 or 2 oxygen atoms or NH groups. A process according to claim 1, wherein the reductive amination of 2,2,6,6-tetramethyl-4-piperidone is carried out by using an amine of the formula (III) in which n is 1 or 2 and, if n is 1, R is C₁-C₈-alkyl, cyclohexyl, tetrahydrofurfuryl, 2,2,6,6-tetramethyl-4-piperidyl or C₂-C₃-alkyl which is monosubstituted by C₁-C₄-alkyloxy or by di(C₁-C₄-alkyl)amino, and, if n is 2, R is C₂-C₆-alkylene or C₄-C₁₀-alkylene which is interrupted by 1 or 2 oxygen atoms or NH groups. A process according to claim 1, wherein the reductive amination of 2,2,6,6-tetramethyl-4-piperidone is carried out by using an amine of the formula (III) in which n is 1 or 2 and, if n is 1, R is C₁-C₈-alkyl, cyclohexyl, 2,2,6,6-tetramethyl-4-piperidyl, 3-methoxypropyl, 3-dimethyl-aminopropyl or 3-diethylaminopropyl, and, if n is 2, R is C₂-C₆-alkylene. A process according to claim 1, wherein the reductive amination of 2,2,6,6-tetramethyl-4-piperidone is carried out by using an amine of the formula (III) in which n is 1 or 2 and, if n is 1, R is C₁-C₈-alkyl or 3-diethylaminopropyl and, if n is 2, R is -(CH₂)₂₋₆-.

Inventors: CASSANDRINI PAOLO DR, RIGHINI GIORDANO, VIGNALI GRAZIANO, CASSANDRINI, PAOLO, DR., RIGHINI, GIORDANO, VIGNALI, GRAZIANO
Applicants: CIBA GEIGY AG, CIBA GEIGY SPA, CIBA-GEIGY AG, CIBA-GEIGY S.P.A.
Application year: 1988
Main classification: C07D211
IPC codes: C07D211, C08K5, C07D405