PROCESS FOR THE PREPARATION OF PIPERIDINE COMPOUNDS

Abstract

The present invention relates to a process for the preparation of a compound of Formula (see Formula) (1), wherein R1 and R2 are, independently of each other, C1-C8 alkyl, comprising reacting a compound of Formula (see Formula) (2), with a source of formaldehyde in the presence of a palladium or platinum catalyst at a hydrogen pressure of 5×108 mPa to 200×108 mPa.

Description

PROCESS FOR THE PREPARATION OF PIPERIDINE COMPOUNDS Description The present invention relates to a process for the preparation of N-methylated piperidine-containing compounds of Formula (1) as provided herein, by reacting the corresponding NH piperidine-containing compounds of Formula (2) with a source of formaldehyde in the presence of a palladium or platinum catalyst at a hydrogen pressure of 5 x 10⁸ mPa to 200 x 10⁻¹ mPa. The compounds in Formula (1) can be used to prepare hindered amine light stabilizers (HALS), which are in turn used to stabilize plastics against degradation induced by light, heat, or oxidation. Examples of such HALS are those in Formulas (3) and (5) provided below. A common process for the N-methylation of piperidine compounds is disclosed in EP-A-729 947, where N-methylation is carried out with formaldehyde and formic acid (Eschweiler-Clarke reaction). Because an excess of formic acid is usually used and the reaction is followed by a neutralization step with a base, the process generates a certain amount of waste. In general, processes for the N-alkylation of amine derivatives by transition metal-catalyzed reductive amination with hydrogen and an aldehyde source are known, but dehalogenation reactions would be expected to result if applied to compounds comprising halogen-triazines, such as those in Formula (2). It has been found that, according to the process of the present invention, the corresponding dehalogenation reactions can be minimized and the compounds of Formula (1) can be prepared in high yields. The catalysts can be easily recovered and waste generation is minimized. Accordingly, the present invention relates to a process for the preparation of a compound of Formula RLfr / nn / zznz / E / YiAi OI N^N (1), wherein Ri and R2 are, independently of each other, Ci-Csalkyl, comprising reacting a compound of the Formula RLfr / nn / zznz / E / YiAi with a formaldehyde source in the presence of a palladium or platinum catalyst at a hydrogen pressure of 5x108mPa to 200x10® mPa. Ri and R2 are preferred independently over each other. Ci-C4 alkyl, especially butyl, is preferred. n-Butyl is preferred to a greater extent. The term formaldehyde source is used for compounds that release formaldehyde for further reaction. Examples of formaldehyde sources include paraformaldehyde, formaldehyde, and methanol. Paraformaldehyde and formaldehyde are preferred, especially paraformaldehyde. Formaldehyde is preferably used in the form of formalin (an aqueous solution of formaldehyde; for example, corresponding 30 to 40% by weight solutions, optionally stabilized with methanol). Typically, the molar ratio of the formaldehyde source to the compound of Formula (2) is from 1:1 to 10:1, especially from 1:1 to 5:1 and, more preferably, from 1:1 to 3:1. A hydrogen pressure of 10 x 10⁸ mPa to 150 x 10⁸ mPa is preferred, especially from 20 x 10⁸ mPa to 150 x 10⁸ mPa. According to one embodiment of the present invention, the hydrogen pressure is from 10 x 10⁸ mPa to 50 x 10⁸ mPa, especially from 20 x 10⁸ mPa to 50 x 10⁸ mPa. Preferably, the process is carried out at temperatures of 50 to 180°C, especially 80 to 150°C. Temperatures of 90 to 140°C are preferred. The process can be carried out with or without a solvent. Generally, the process is performed in the presence of a solvent, such as water or an organic solvent. Examples of organic solvents include aliphatic solvents, aromatic solvents, and alcohols, such as pentane, hexane, heptane, octane, decane, cyclopentane, cyclohexane, methylcyclohexane, petroleum ether, benzene, toluene, xylene, ethylbenzene, eumene, bromobenzene, chlorobenzene, dichlorobenzene, furan, methanol, ethanol, n-propanol, and isopropanol, preferably hexane, methanol, toluene, and xylene. Water, hexane, methanol, toluene, and xylene are preferred solvents, with methanol, toluene, and xylene being the preferred options. Toluene and xylene are preferred, especially xylene. The amount of solvent that can be used for the inventive process is, for example, 10 to 95% by weight, especially 20 to 90% by weight, and more preferably 40 to 90% by weight, depending on the weight of the reaction mixture. An amount of 40 to 90% by weight is most preferred. Supported palladium (Pd) or platinum (Pt) catalysts are preferred. These typically comprise elemental Pd or Pt supported on a suitable carrier. Any known carrier material can be used, such as carbon, calcium carbonate, aluminum oxide, titanium dioxide, or natural or synthetic zeolites, especially carbon. Palladium or platinum catalysts supported on a carbon carrier are preferred. In general, according to one embodiment of the present invention, palladium catalysts, such as those supported on a carbon carrier, are used. Likewise, according to a further embodiment of the present invention, platinum catalysts, such as those supported on a carbon carrier, are used. The amount of palladium or platinum in these supported catalysts is, for example, 0.1 to 20% by weight, and in particular, 1 to 20% by weight, depending on the weight of the supported catalyst. An amount of 2 to 15% by weight is preferred. The amount of catalyst to be used for the inventive process is, for example, 0.5 to 20% by weight, in particular, 2 to 15% by weight, depending on the weight of the compound in Formula (2). The process according to the present invention can be carried out continuously or discontinuously, for example, in batches. The reaction time depends on the reaction conditions and can be, for example, from 2 to 40 hours, especially from 6 to 40 hours. The preferred upper limits are 24 hours and, even more preferably, 12 hours. According to a preferred embodiment of the present invention, a compound of Formula (2), wherein Ri and R2 are n-butyl, is reacted with paraformaldehyde or formaldehyde in the presence of a palladium or platinum catalyst supported on a carbon carrier and a solvent, such as water, methanol, toluene or xylene, at a hydrogen pressure of 10x108mPa to 150x108mPa and a temperature of 80 to 150°C. Regarding this form of implementation, the definitions and preferences provided above in this document will apply. The compounds of Formula (2) are known and can be prepared, for example, in accordance with EP 455 588, Example 1 A). The mixture obtained after preparing the compound of Formula (1) can be used directly for further conversions of the compound of Formula (1), typically after separating the catalysts. No further purification steps are required. The compounds of Formula (1) prepared according to the inventive process can be used for the preparation of HALS, such as those of the following Formulas (3) and (5) f3f3 R3—NH—(CH2)3--N----(CH2)2--N-----(CH2)3---NH---R3(3), RLfr / ηη / ζζητύβ / υιλι where R3 is a group of the Formula RLfr / nn / zznz / E / YiAi where Ri and R2 are as defined above herein, and R4 and Rs are hydrogen or methyl. The compounds of Formula (3) are commercially available, i.e., as Chimassorb® 119, and can be obtained by preparing a compound of Formula (1) according to inventive process 25 and by reacting said compound of Formula (1) with a compound of Formula NH2----(CH2)3---NH---(CH2)2--NH----(CH2)3---NH2(6). The reaction is preferably carried out in an aromatic hydrocarbon solvent, for example, toluene, xylene, or trimethylbenzene, at temperatures of 50 to 200°C, preferably 100 to 200°C. The hydrochloric acid released in the reaction is preferably neutralized with an inorganic base, for example, potassium or sodium carbonate or hydroxide, in an amount at least equivalent to that of the acid released. The compounds of Formula (5) can be obtained by preparing a compound of Formula (1) 35 according to the inventive process and by reacting said compound of Formula (1) with a compound of Formula where R4 and Rs are hydrogen or methyl. (7), The reaction conditions for the preparation of the compound of Formula (5) may correspond to those provided above for the compounds of Formula (3). The compounds in Formulas (3) and (5) are effective stabilizers for organic materials against the damaging effects of light and heat, especially for synthetic polymers such as polyolefins. For example, films, such as agricultural films, produced with polyolefins are stabilized with hindered amine stabilizers to improve the long-term stability of the films. EXAMPLES Example 1: Preparation of the compound of Formula (102) Cl nrj n-butyl .... 1 A.. rj ··' I n-butyl 11 :CI GIL HC 1 H.;C “Ή ” ' cu. Hc” ' fl ”” CHj HH 1101: l rj - N A n-butylNn-butyl 'fiN <102! A pressure steel autoclave was sequentially charged with 0.8 g of Pd / C (5 wt% Pd, based on the weight of the Pd / C catalyst; 4.9 wt% Pd / C with respect to the weight of the compound of Formula (101)), 2.3 g of paraformaldehyde (76.7 mmol), and 60.0 g of a 27 wt% solution of the compound of Formula (101) in xylene (30.2 mmol of the compound of Formula (101)). After purging the reaction vessel with nitrogen, the system was heated to 100°C, pressurized with 30 x 10⁸ mPa of hydrogen gas at this temperature, and stirred for 24 hours. After the total reaction, the system was vented, purged with nitrogen, and cooled to room temperature to obtain the target compound of Formula (102) with a yield of 97.1%. Example 2: Example 1 was repeated, but a hydrogen pressure of 20 x 10⁸ mPa was used (instead of 30 x 10⁸ mPa). The compound of Formula (102) was obtained with a yield of 96.7%. Example 3: Example 1 was repeated, but a hydrogen pressure of 180 x 10⁸ mPa was used (instead of 30 x 10⁸ mPa). The compound of Formula (102) was obtained with a yield of 97.4%. Example 4: Example 1 was repeated, but a hydrogen pressure of 20 x 10⁸ mPa (instead of 30 x 10⁸ mPa) and an equimolar amount of a 37 wt% aqueous formalin solution (instead of 2.3 g of paraformaldehyde) were used. The compound of Formula (102) was obtained in a 97.1% yield. Example 5: Example 1 was repeated, but a hydrogen pressure of 180 x 10⁸ mPa (instead of 30 x 10⁸ mPa), a reaction time of 12 hours (instead of 24 hours), and 10 wt% Pd / C (instead of 4.9 wt% Pd / C) were used. The compound of Formula (102) was obtained in a yield of 98.8%. Example 6: Example 1 was repeated, but a hydrogen pressure of 100 x 10⁸ mPa (instead of 30 x 10⁸ mPa) and 10 wt% Pt / C (instead of 4.9 wt% Pd / C) were used. The compound of Formula (102) was obtained in a yield of 96.3%. Example 7: Example 1 was repeated, but a reaction temperature of 130°C (instead of 100°C), an equimolar amount of 37 wt% aqueous formalin solution (instead of 2.3 g of paraformaldehyde), and 10 wt% Pt / C (instead of 4.9 wt% Pd / C) were used. The compound of Formula (102) was obtained in a yield of 96.7%. In none of Examples 1 to 7 could dehalogenated by-products be detected. Comparative example 1: Preparation with Raney's Cu as a catalyst Example 1 was repeated, but 10 wt% Raney Cu was used (instead of 4.9 wt% Pd / C). The compound of Formula (102) was obtained in a yield of 9.6%. Comparative example 2: Preparation with Raney's Co as a catalyst Example 1 was repeated, but 10 wt% Raney Co was used (instead of 4.9 wt% Pd / C). The compound of Formula (102) was obtained in a yield of 2.5%. Comparative example 3: Preparation with Raney Ni as a catalyst Example 1 was repeated, but 10 wt% Raney Ni was used (instead of 4.9 wt% Pd / C). The compound of Formula (102) was obtained in a yield of 8.0%.

Claims

1. Process for the preparation of a compound of Formula (1), RLfr / nn / zznz / E / YiAi wherein Ri and Rg are, independently of each other, Ci-Csalkyl, comprising reacting a compound of Formula Cl with a source of formaldehyde in the presence of a palladium or platinum catalyst at a hydrogen pressure of 5x108 mPa to 200x108 mPa.

2. A process according to claim 1, wherein Ri and R2 are, independently of each other, C1-C4 alkyl, preferably butyl.

3. A process according to claim 1 or 2, wherein the source of formaldehyde is paraformaldehyde or formaldehyde.

4. A process according to any of claims 1 to 3, wherein the process is carried out at a temperature of 50 to 180°C.

5. A process according to any of claims 1 to 3, wherein the process is carried out at a temperature of 80 to 150°C.

6. A process according to any of claims 1 to 5, wherein a palladium or platinum catalyst supported on a carbon carrier is used.

7. A process according to any of claims 1 to 5, wherein a palladium catalyst supported on a carbon carrier is used.

8. A process according to any of claims 1 to 5, wherein a platinum catalyst supported on a carbon carrier is used.

9. A process according to any of claims 1 to 8, wherein 2 to 15% by weight of the catalyst is used, depending on the weight of the compound of Formula (2).

10. A process according to any of claims 1 to 9, wherein the reaction is carried out in the presence of a solvent.

11. A process according to claim 10, wherein the solvent is water, hexane, methanol, toluene or xylene, preferably methanol, toluene or xylene.

12. Use of the compounds of Formula (1) obtained according to the process according to claim 1 for the preparation of the compounds of Formula RLfr / nn / zznz / E / YiAi Γ ?3 R3--NH—(CH2)3 N----(CH2)2 N-----(CH2)3---NH---R3 (3), wherein Rs is a group of Formula (4) or for the preparation of the compounds of Formula (5) and wherein Ri and R2 are as defined in claim 1, and R4 and Rs are hydrogen or methyl.