JPS5943950B2 - Method for producing N-substituted piperidinol derivatives - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing N-substituted piperidinol derivatives.

More specifically, the present invention relates to a method for producing N-substituted piperidinol derivatives having large steric hindrance. In general, N-substituted piperidinol derivatives with large steric hindrance exhibit excellent stabilizing effects against photodegradation of various polymeric materials, particularly polyurethane.

As a method for producing such N-substituted piperidinol derivatives, a polysubstituted piperidinol and a substituted or unsubstituted alkylating agent such as an aliphatic halide are combined with a nonpolar solvent such as xylene, toluene, or cumene, or dimethylformamide, A method is known in which the reaction is carried out in a polar solvent such as dimethylacetamide in the presence of a deoxidizing agent such as sodium hydroxide, sodium carbonate, or amines.

However, when polysubstituted piperidinols are reacted with a substituted or unsubstituted alkylating agent in the presence of a deoxidizing agent in a nonpolar solvent such as the above-mentioned cumene, these solvents have low solubility for the polysubstituted piperidinols, and Because of its low polarity, the reaction rate is usually about 10%, which is very poor. On the other hand, if the reaction is carried out with a substituted or unsubstituted alkylating agent in the presence of a deoxidizing agent in a polar solvent such as dimethylformamide as mentioned above, a considerably high reaction rate can be obtained, but along with this, the 0-benzylated product, N There is a drawback that by-products such as -,0-dibenzylated products are produced.

An object of the present invention is to provide a method for producing N-substituted piperidinol derivatives with high reaction rate and high selectivity.

The object of the present invention is to react polysubstituted-4-piperidinol represented by the general formula (1) (in which R1 and R2 represent the same or different alkyl groups) with a substituted or unsubstituted alkylating agent. This can be achieved by using a solvent selected from the group consisting of sulfolanes and mononitrobenzenes as a reaction medium when producing N-substituted piperidinol derivatives, and if necessary coexisting a deoxidizing agent in the reaction system. .

Furthermore, the above object of the present invention is more preferably achieved by coexisting water in the reaction system. R1 and R2 of the polysubstituted 4-piperidinol represented by the general formula (1), which is the starting material in the method of the present invention, are the same or different alkyl groups as described above, but usually are alkyl groups having 1 to 18 carbon atoms. are preferred, and lower alkyl groups such as methyl, ethyl, and propyl groups are particularly preferred.

Specific compounds include 2,2,6,6-tetramethyl-4-piperidinol, 2,2,6-trimethyl-6-
Ethyl-4-piperidinol, 2.2.6-trimethyl-6-propyl-4-piperidinol, 2.2-dimethyl-6.6-diethyl-4-piperidinol, etc., but especially 2.2.6. 6-tetramethyl-
4-piperidinol is preferred.

The method for producing such polysubstituted-4-piperidinol is not particularly limited, but for example, the method shown in the reaction formula below, which is a combination of the methods described in JP-A-53-1294 and the literature cited therein; Manufactured by. The substituted or unsubstituted alkylating agent used in the method of the present invention means a reagent that alkylates the hydrogen atom bonded to the nitrogen atom of the piperidinol derivative molecule, and causes a reaction according to the following formula. Essentially, anything is fine as long as it can be used.

Here, z represents a substituted or unsubstituted alkyl group such as an alkyl group, and x represents a denailing reaction, ie, a deacidification reactive functional group such as a halogen.

The substituted or unsubstituted alkyl group in these substituted or unsubstituted alkylating agents means an organic group in which the carbon bonded to the deoxidizing functional group is an aliphatic carbon.

Further, as the deoxidizing reactive functional group, an appropriate acid residue can be used, but halogen is usually preferably used. Aliphatic halides are therefore preferred substituted or unsubstituted alkylating agents. Specifically, alkyl halides (methyl chloride, ethyl bromide, isopropyl iodide, n-hexyl chloride, octyl bromide, 2
- ethylhexyl chloride, dodecyl iodide, etc.); alkenyl halides (allyl chloride, allyl bromide, allyl iodide, butenyl chloride, isoprenyl chloride, etc.), aralkyl halides such as benzyl halide, p-methylbenzyl halide, α-methylbenzyl halide ( Halides include chloride, bromide, iodide, etc.): hydroxyl group-substituted alkyl halides, such as 2-hydroxyethyl chloride, 2-hydroxyethyl bromide, 3-hydroxypropyl chloride; epoxy group-substituted alkyl halides, such as 2,3 epoxy n-propyl bromide, etc. Illustrated. Preferred are aralkyl halides, particularly preferred are benzyl halides. One of the features of the present invention is that a solvent selected from the group consisting of sulfolanes and nitrobenzenes is used as the reaction medium. Sulfolanes are compounds containing 〉S// in the molecule, specifically, the following \o ゛ general formula (2
) and (3) where R3 and R4 are alkyl groups, and R5 is an alkylene group or an alkyl-substituted alkylene group.

Examples of the alkyl groups R3 and R4 in general formula (2) include alkyl groups having 1 to 12 carbon atoms, such as methyl, ethyl, n- or isopropyl, n- or Sec-butyl, hexyl, octyl, 2-ethylhexyl, dodecyl The following groups are exemplified.

The alkylene group represented by R7 has 5 to 12 carbon atoms.
An example of the alkylene group is a tetramethylene group, and an example of an alkyl-substituted alkylene group is an alkyl-substituted group of an alkylene group having 5 to 12 carbon atoms, such as a 3-methyltetramethylene group.

Examples of the compound represented by the general formula (2) include dimethylsulfone, diethylsulfone, and methylethylsulfone.

Examples of the compound represented by the general formula (3) include tetramethylene sulfone (commonly known as sulfolane or TMSO) and 3-methyl-tetramethylene sulfone (commonly known as 3-methylsulfolane). This may be a mixture. Among these sulfolanes, preferred are tetramethylene sulfone and 3-methyl-tetramethylene sulfone, and particularly preferred is tetramethylene sulfone. Mononitrobenzenes used as reaction medium include mononitrobenzene and substituted mononitrobenzenes, such as alkyl-substituted mononitrobenzenes (1-
(nitro-2-methyl-benzene, 1-nitro-3-ethylbenzene, etc.).

Among these, preferred are mononitrobenzene, 1-
Nitro-2-methylbenzene is particularly preferred, and mononitrobenzene is particularly preferred. Sulfolanes and nitrobenzenes can be used in combination. Other non-polar solvents (xylene, toluene, cumene, etc.), polar solvents (dimethylformamide, dimethylacetamide, etc.), etc. can be used in combination with the sulfolanes or nitrobenzenes as long as the effects of the present invention are not impaired.

When used in combination, the amount used is usually 30% or less in the case of a nonpolar solvent, and usually 10% or less in the case of a polar solvent, based on the weight of the total organic solvent. Examples of the deoxidizing agent used as necessary in the method of the present invention include carbonates of alkali metals (potassium carbonate, sodium carbonate, lithium carbonate, etc.).

Among these, preferred are sodium carbonate and potassium carbonate, and particularly preferred is potassium carbonate. In carrying out the method of the present invention, polysubstituted-4-piperidinol (A) and a substituted or unsubstituted alkylating agent (
The molar ratio with B) can be varied depending on the reaction conditions (especially the presence or absence of a deoxidizing agent).

When no deoxidizer is used, the molar ratio of (A) and (B) is usually (A):(B)-1.0 to 10:1.0, preferably (A):(B)- 1.5-3, O: 1.0. When no deoxidizing agent is used, in addition to (A) participating as a reaction component, excess (A) is considered to have the same effect as the deoxidizing agent. In addition, when using a deoxidizing agent, usually (A)
:(B)-1.0:0.7-5.0, preferably (A):(B)-1.0:0.9-3.0. In this case, the ratio of (A) and deoxidizing agent (C) is usually (A):
(C)-1.0: 0.4 to 5.0, preferably (
A):(C)-1.0:0.7 to 2.0. solvent(
The amount of organic solvent used is not particularly limited, but it is preferably an amount that dissolves the reaction mixture or makes it into a slurry.

Specifically, the amount of solvent is usually 10% based on the weight of the entire reaction system.
~80%, preferably 30-60%. The order in which each component is added or added is not particularly limited.

For example, there is a method in which the solvent is first charged and (A) and, if necessary, a deoxidizing agent are added while stirring, and then (B) is added dropwise, or a method in which the reaction components are added to the solvent all at once. The reaction temperature is usually 100 to 250°C, preferably 12
The temperature is 0 to 200°C.

The reaction time is usually 0.5 to 10 hours, preferably 2 to 8 hours. The reaction can be carried out under reduced pressure, normal pressure, or increased pressure. The reaction pressure is usually 10 to 20 mmHg to 2
0kg/CJ gauge, preferably 1.0~10k
9/Cd gauge. The reaction is usually carried out under stirring,
This is carried out while passing nitrogen gas if necessary. In the method of the present invention, if water is allowed to coexist in the reaction system from the start of the reaction, the reaction rate becomes significantly faster, and the reaction rate and yield of the target product can be increased. Furthermore, since the presence of water has the effect of accelerating the reaction rate, the reaction temperature can be lowered, and as a result, the production of by-products can be reduced. When water is present, the amount of water is usually 0.5 to 40% based on the total weight of the system at the start of the reaction, preferably 3%.
, 0 to 25%, and the amount of water relative to the total amount of (A) and (B) is usually 1.4 to 400%.

Also, the ratio of organic solvent to water is usually organic solvent: water = 100:
It is 1.0-160. The method of adding water is not particularly limited, and it may be added all at once when other ingredients are added, or it may be added while stirring after other ingredients are added. The reaction conditions for the reaction carried out in the presence of water are the same as described above, but the reaction temperature can be lowered and is usually 50 to 150°C, preferably 80 to 130°C. After the reaction is completed, the target N-substituted piperidinol derivative is extracted from the reaction product.

The extraction method is not particularly limited, and for example, after the reaction is complete, if necessary, the water contained in the reaction system is distilled off under reduced pressure, the by-product salts are removed by filtration, and then the precipitated N-substituted piperidinol derivative is removed by cooling. A method in which the by-product salts are extracted with water after the reaction is completed, and the precipitated N-substituted piperidinol derivative is extracted by a filtration method; After the reaction is completed, the salts are removed by the above method. , a method in which the solvent is distilled off under reduced pressure and then dried to obtain an N-substituted piperidinol derivative; Examples include a method of extracting the N-substituted piperidinol derivative with an organic solvent such as alcohol. The method of the present invention makes it possible to selectively react with the N-position of polysubstituted piperidinols, thereby suppressing the formation of by-products and producing the desired N-substituted piperidinol derivatives in high yields ( The yield of the conventional method is, for example, 5 to 30%, whereas the yield of the method of the present invention is improved to, for example, 50 to 70%), and by coexisting water in the reaction system. As a result, the reaction rate is significantly increased, which makes it possible to relax the reaction conditions, and as a result, the desired N-mono-substituted piperidinol derivative can be produced with higher selectivity and yield (yield ratio, e.g., 75-90%). It brings about the effect of being able to do it.

The N-monosubstituted piperidinol derivatives obtained by the method of the present invention can be used to synthesize various synthetic polymers (olefin polymers or copolymers, polyvinyl chloride polymers or copolymers, polyesters, polyacetals, polyamides, polyurethanes, etc.). Shows excellent stabilizing effect against deterioration.

Therefore, it is useful as a weathering agent for those polymeric substances. In this case, it can be used either as an additive type or as a reactive type. The methods for using these are known, such as JP-A No. 50-5434, German Unexamined Publication No. 1929928, German Publication No. 2258752, and JP-A No. 1977-48.
Examples include methods described in Japanese Patent No. 55938 and Japanese Patent No. 5315385.

The present invention will be further explained below with reference to Examples and Comparative Examples, but the present invention is not limited thereto. Example 1 2.2.
6,6-tetramethyl-4-piperidinol 407 (0
．． 255 mol), benzyl chloride 357 (0.27
mol), 28.6 mols of sodium carbonate (0.27 mols) and 98 ml of tetramethylene sulfone were added and the mixture was stirred for 17 mols.
The reaction was carried out at 0°C for 4 hours.

After the reaction was completed, it was cooled to 90°C, and the salts produced as by-products were separated at 90°C, and the liquid was analyzed by gas chromatography to find that N-
The production rate of benzyl-2,2,6,6-tetramethyl-4-piperidinol was 81% (based on 2,2,6,6-tetramethyl-4-piperidinol), and 0-benzylated product, N-, The by-products of 0-dibenzylated products are 2.
5.1%. Next, after adding ethyl acetate 407 to the solution ▲, it was cooled to 20°C over 3 hours with gentle stirring, and the precipitated N-benzyl-2,2,6,6-tetramethyl-4-piperidinol was centrifuged ▲ It was taken out by filtration and dried at 90° C. for 5 hours under a reduced pressure of 10 to 20 degrees Hg. N-benzyl-2,2,6,6-tetramethyl-4-piperidinol with a purity of 94% was obtained in a yield of 63%. Example 2 2,2,6,6-tetramethyl-4-piperidinol 40 (0,255 mol), benzyl chloride 167 (0.13 mol) and nitrobenzene 757 were charged into the same apparatus as in Example 1 and heated to 180°C. The mixture was reacted for 4 hours with stirring.

After the reaction was completed, the mixture was cooled to 90° C., 100 ml of water was added, and the mixture was thoroughly stirred. After stirring, the mixture was allowed to stand and separated into an aqueous layer and an organic layer.
When the organic layer was analyzed by gas chromatography, the production rate of N-benzyl-2,2,6,6-tetramethyl-4-piperidinol was 79% (based on benzyl chloride), and the production rate of N-benzyl-2,2,6,6-tetramethyl-4-piperidinol was 79% (based on benzyl chloride). The production rate of O-dibenzylated products was 1% or less in each case. Next, the organic layer was cooled to 20° C. over 3 hours with gentle stirring. The precipitated crystals are taken out by centrifugation (the nitrobenzene adhering to the crystals is thoroughly washed with petroleum ether)13.
It was dried at 0° C. for 8 hours at 10-20 mmHg. 96% purity N-benzyl-2,2,6,6tetramethyl-
4-piperidinol was obtained with a yield of 65%. Example
3 Into an 11 stainless steel autoclave equipped with a stirrer, 2,2,6,6-tetramethyl-4-piperidinol 407 (0.255 mol), benzyl chloride 64 (0.5 mol), potassium carbonate 357 ( 0.254 mol), 987 mol of tetramethylene sulfone, and 327 mol of water were charged, and the mixture was reacted at 110° C. for 4 hours with stirring.

The pressurization at this time was 3 to 3.5 kg/Cni gauge. After the reaction was completed, the system was cooled to 80 to 90°C, water contained in the system was distilled off under reduced pressure, and precipitated salts were separated. ▲
When the liquid was analyzed by gas chromatography, N-benzyl-
The production rate of 2,2,6,6-tetramethyl-4-piperidinol was 94%, and the by-products of O-benzylated product and N-,O-dibenzylated product were 1% and 3% or less, respectively. Next, petroleum ether 10007 was added and the precipitated crystals were taken out by centrifugation and kept at 100°C for 8 hours for 10 to 20 minutes.
Dry to mmHg. 95% purity N-benzyl-2.2
・6,6-tetramethyl-4-piperidinol yield 8
It was obtained at 6%. Example 4 In the same autoclave as in Example 3, 2,2,6,6-tetramethyl-4-piperidinol 40'! (0.255 mol), lauryl bromide 867 (0.5 mol), potassium carbonate 357 (0.254 mol), tetramethylene sulfone 987 and water 167 while stirring.
The reaction was carried out at ℃ for 5 hours.

After the reaction was completed, the reaction was carried out under reduced pressure (10
Water and tetramethylene sulfone were distilled off and dried at 80 to 130° C. (~1 mmHg). From the dried product, N-lauryl-2,2,6,6-tetramethyl-4-piperidinol was obtained in a yield of 88% using ethyl alcohol.
Comparative Example 1 In the same apparatus as in Example 1, 40 units of 2,2,6,6-tetramethyl-4-piperidinol (0.255 mol), 357 units of benzyl chloride (0.277 mols), and 277 units of sodium carbonate (0.2 units) were added. 26 mol) and 100 cumene were charged and reacted at 175°C for 10 hours.

After the reaction was completed, the mixture was cooled to 90°C and filtered at that temperature.
Gas chromatography analysis of the liquid revealed that the production rate of N-benzyl-2,2,6,6-tetramethyl-4-piperidinol was 11.4%. Comparative Example 2 In an apparatus similar to Example 1, 407 (0.255 mol) of 2,2,6,6-tetramethyl-4-piperidinol, 357 (0.277 mol) of benzyl chloride, and 27.6 mol of sodium carbonate ( 0.26 mol) and dimethylformamide 987 were charged and reacted at 160°C for 6 hours.

Claims (1)

[Claims] 1 General formula (1) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(1) (However, in the formula R
^1 and R^2 represent the same or different alkyl groups)
When producing an N-substituted piperidinol derivative by reacting the polysubstituted-4-piperidinol shown in (1) with a substituted or unsubstituted alkylating agent, a solvent selected from the group consisting of sulfolanes and mononitrobenzenes is added to the reaction system. A method for producing an N-substituted piperidinol derivative, which is characterized by the presence of N-substituted piperidinol derivatives. 2. The method according to claim 1, characterized in that a deoxidizing agent is present in the reaction system. 3. The method according to claim 1 or 2, characterized in that water is allowed to coexist in the reaction system. 4. The method according to claim 3, wherein the amount of water coexisting in the reaction system is 0.5 to 40% by weight based on the weight of the entire reaction system. 5. The method according to any one of claims 1 to 4, wherein the sulfolane is tetramethylene sulfone. 6. The method according to any one of claims 1 to 5, wherein the substituted or unsubstituted alkylating agent is an aliphatic halide. 7. The method according to claim 6, wherein the aliphatic halide is an alkyl halide. 8. The method according to claim 6, wherein the aliphatic halide is an aralkyl halide. 9. The method according to claim 2, 7, or 8, wherein the deoxidizing agent is an alkali metal carbonate.