JPH02167260A - Production of 1-halo-4-(n-acyl-n-alkylamino)-2,2,6,6-tetraalkylpiperidine - Google Patents

Abstract

PURPOSE:To industrially advantageously obtain the subject compound useful as a bleaching agent, etc., in a high yield and high purity by adding halogen and reacting in a solvent containing 4-(N-acyl-N-alkylamino)-2,2,6,6- tetraalkylpiperidine and in the presence of alkali. CONSTITUTION:Halogen (especially Cl, Br or I is preferable) is added in a solvent containing a compound expressed by formula I (R<1>-R<4> are 1-4C alkyl; R<5> is alkyl or cycloalkyl, etc.; R<6> is alkyl) in the presence of alkali such as NaOH or KOH and reacted to obtain 1-halo-4-(N-acyl-N-alkylamino)-2,2,6,6- tetraalkylpiperidine expressed by formula II (X is halogen). The reaction is performed by dispersing the compound expressed by formula I in a solvent such as water or methylene chloride in a concentration of usually 5-50wt.%, preferably 20-40wt.%.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to the production of 1-hero-4-(N-acyl-N-alkyl ξ))-2,2,6,6-tetraalkylpiperidine. Regarding the method.

Pressure and pressure 1-halo 4-(N-acyl-N-alkylamino)
-2,2,6,6-titraalkylbiperidines are useful as components of bleaches and disinfectants.

Conventionally, regarding the method of halogenating the hydrogen on the nitrogen of the piperidine ring, for example, Japanese Patent Application Laid-Open No. 47-25718 describes a method in which a solution of 2,2,6,6-titramethylbiperidine in an aqueous or alcohol solution is cooled with water, A method is known in which an aqueous hypochlorite solution is added to the mixture while stirring to cause a reaction.

Furthermore, as an example of halogenation at the 1-position of a piperidine derivative substituted at the 4-position, bis(2,2,6,6-tetramethyl- A method is known in which 4-piperidyl) sebacate is reacted with tert-butoxy chloride.

However, no method for industrially advantageous production of 1-halo 4-(N-acyl-N-alkylamino)-2,2,6,6-titraalkylbiperidine has been known so far.

The present inventors have made extensive efforts to find a method for industrially advantageous production of 1-halo 4-(N-acyl N-alkylamino)-2,2,6,6-tetraalkylpiperidine. As a result of research, 4-(N-acyl-N-alkylamino) -
1-halo 4-(N-acyl-N-alkylaξ)) by adding a halogen in the presence of an alkali in a solvent containing 2,2,6,6-titraalkylbiveridine
The present invention was achieved by discovering that -2,2,6,6 tetraalkylbiperidine can be produced with high purity and high yield.

The present invention is based on the general formula (I) (wherein R', Rt, R3 and R4 each independently represent an alkyl group having 1 to 4 carbon atoms, R5 is an alkyl group,
It represents a cycloalkyl group or an aralkyl group, and R6 represents an alkyl group. ) 4-(N-acyl-N-alkylamino) represented by
A halogen is added to a solvent containing -2,2,6,6-tetraalkylpiperidine in the presence of an alkali to form a compound of the general formula (II) (wherein RISRl, R1, R4, RS and R6 are the same as above). In particular, the present invention is characterized by obtaining 1-halo-4-(N-acyl-N-alkylamino)-2,2,6,6-titraalkyl-lepiveridine represented by According to 4-(N-acyl-N-alkylatan))-2,2,6,6-titraalkylbiveridine by bubbling chlorine in the presence of an alkali into a solvent containing l-chloro -4-(N-acyl-N-alkyl ξ)) -2,2,6,6=tetraalkylpiperidine can be obtained with high purity and high yield.

4-(N-acyl-N-
alkylamino)-2,2,6,6-tetraalkylpiperidine, R1, R3 and R4 each independently represent an alkyl group having 1 to 4 carbon atoms, preferably a methyl group or an ethyl group, Particularly preferred is a methyl group. These may be the same or different. R5 is an alkyl group having 1 to 4 carbon atoms, or an alkyl group having 6 to 4 carbon atoms.
12 cycloalkyl groups or aralkyl groups, and preferred examples include methyl, ethyl, and cyclohexyl groups. R6 represents an alkyl group having 1 to 4 carbon atoms, preferably a methyl group or an ethyl group.

Therefore, as a particularly preferable example represented by the above general formula (1), 4-(N-acetyl-Nmethylamino)
-2,2,6,6-titramethylpiperidine, 4-(N
-acetyl-N-ethyl))-2,2,6,6-titramethylpiperidine, 4-(N-propionyl-N-
methylamino)-2,2,6,6-titramethylpiperidine, and the like.

4-(N-acyl-N-alkylamino) - 2,2,6,6-thitraalkylpiveridine is dispersed in the solvent described below at a concentration of usually 5 to 50% by weight, preferably 20 to 40% by weight,
It is considered a slurry.

As the solvent, water or a mixture of water and an organic solvent immiscible therewith is used. When water is used as a solvent, 4-(N-acyl-
N-alkylamino)-2°2.6.6-tetraalkylpiperidine is dispersed and the reaction is carried out in a slurry state. On the other hand, when a mixture of water and an immiscible organic solvent is used as the solvent, the reaction similarly proceeds with 4-(N-acyl-N-alkylamino)2 in the mixed solvent.
．． 2.6.6-Titraalkylbiveridine is dispersed,
The reaction is carried out in a slurry state or in a heterogeneous two-phase system. The organic solvent is not particularly limited as long as it does not have a harmful effect on the reaction, but aliphatic lower halogenated hydrocarbons having 1 to 3 carbon atoms such as methylene chloride and dichloroethane are usually preferably used. .

As the alkali, alkali metal hydroxides or alkaline earth metal hydroxides are preferably used, and sodium hydroxide, potassium hydroxide, calcium hydroxide, etc. are particularly frequently used. The amount of alkali used is usually 4-(N-acyl-N-alkylamino)-2,2
, 1-1 for 6,6-tetraalkylpiperidine
It is 0 times the molar amount, preferably 1.1 to 3 times the molar amount.

According to the invention, 4-(N-acyl-N-
A halogen is added to a solvent containing (alkylamino)-2,2,6,6-tetraalkylpiperidine in the presence of an alkali, and the mixture is reacted with stirring. As the halogen, chlorine, bromine or iodine is used depending on the desired halide, but according to the present invention, in particular, by using chlorine, 1-chloro-4-(N-acyl-N- 2.2,6.6-titraalkylbiperidine can be obtained with high purity and high yield.

In the above method, when chlorine is used as the halogen, 4-(N-acyl-N-alkylamino)-2,2
, 6,6-tetraalkylpiperidine. The halogen is usually 1 to 5 times the molar amount, preferably 1.05 to 2 times the amount of 4-(N-acyl-N-alkylamino)-2,2,6,6-tetraalkylpiperidine used. It is used in a range of molar amounts.

The reaction temperature is usually in the range of 10 to 60°C, preferably in the range of 10 to 40°C. Although the reaction is not particularly limited, it is usually 1 to 10 kg/c.
d, preferably under a pressure of 1 to 2 kg/cJ for 1 to 10 hours, preferably for 2 to 4 hours.

Therefore, according to the present invention, 4-(N-acyl-N-alkylamino)-2,2 represented by the general formula (1)
, 6,6-tetraalkylpiperidine, represented by the general formula (U) (wherein R1, R2, R3, R4, R5 and R4 are the same as above, and X represents a halogen atom). l-Ha12-4-(N-acyl-N-alkylamino')-2,2,6,6-tetraalkylpiperidine can be obtained. In the above general formula (ff), X represents a halogen atom, such as chlorine, bromine or iodine, preferably chlorine.

Therefore, according to the present invention, the above-mentioned 4-(N-acyl-
For example, 1-chloro-4-(N
-acetyl-N-methylamino)-2,2,6,6-titramethylbiperidine, 1-chloro-4-(N-acetyl-N-ethylamino))2,2,6,6-titramethyl Piveridine, 1-chloro-4-(N-propionyl-N
-methylamino)-2,2,6,6-titramethylpiperidine and the like can be suitably obtained.

Thus, according to the method of the present invention, 4(N-acyl-N-
Since the reaction is carried out by directly adding halogen to a solvent containing (alkylamino) -2,2,6,6-titraalkylbiperidine in the presence of an alkali, there is no need for an excess alkali, and the reaction can be carried out at room temperature. To obtain the target 1-halo-4-(N-acyl-N-alkylamino)-2,2,6,6-titraalkylbiveridine in high yield and high purity by performing the reaction at high temperature. Can be done.

Next, 4-(N-acyl-N-alkyl ξ))-2,2,6,6-titraalkylpiveridine represented by the general formula (1) is represented by IIIQ formula (III) (wherein,
R1, R1, R3 and R4 are the same as above. ) to 2,2,6.6-tetraalkyl-4-piperidinone represented by hydrogen and general formula (IV) R' in the presence of a catalyst.
An organic amine represented by -N I 4-(N-alkylamino)-2,2゜6.6-tetraalkylpiperidine represented by [] (In the formula, R6 is the same as above.) It can be obtained by reacting an acid anhydride represented by the following formula.

The 2,2,6.6-tetraalkyl-4-piperidinone represented by the above-format (I The method for obtaining -(N-alkylamino)2.2.6.6-tetraalkylpiperidine is disclosed in, for example, JP-A-61-238777 and JP-A-62-030757.
Usually, alcohol or water is used as a solvent, and platinum/activated carbon or palladium/activated carbon is used as a catalyst. -4 expressed in form (V)
(N-alkylamino)-2,2,6,6-tetraalkylpiperidine is an already known compound.

Specifically, for example, 2,2,6.6-tetramethyl-
Methylamine in the presence of the above catalyst to 4-piperidinone,
By reacting ethylamine, propylamine, butylamine, cyclohexylane, β-phenethylamine, etc., the corresponding 4-(N-alkylamino)-2,2,6,6-tetraalkylpiperidine can be obtained. .

After the completion of the reaction, the catalyst is filtered off, and the resulting filtrate is reacted with the acid anhydride represented by the above-mentioned form (VI) as an acylating agent. N
-acyl-N-alkylamino)-2,2,6,6-tetraalkylpiperidine can be obtained. Here,
As the acid anhydride, for example, acetic anhydride and propionic anhydride are preferably used.

After the completion of this acylation reaction, as described above, an alkali is added to the reaction mixture, and if necessary, the organic solvent is added, and then a halogen is added thereto. N alkylamino) -2,2,
6,6-tetraalkylpiperidines can be obtained.

As is clear from the above, from 2,2.6.6-tetraalkyl-4-piperidinone represented by the above-format (1) to 4(N-alkylamino)-2, 2,6,6-tetraalkylpiperidine and 4-(N-acyl-
N-alkylamino)-2゜2.6.6-tetraalkylpiperidine, then l halo 4-(N-acyl-N-
The series of reactions to obtain 22.6.6-tetraalkylpiperidine (alkylamino) can all be carried out using water as a solvent. In the final step of obtaining 1-halo 4-(N-acyl-N-alkylamino)-2,2,6,6-tetraalkylpiperidine, an organic solvent may be added to the reaction mixture from the previous step, if necessary. .

Therefore, according to the present invention, as described above, 2.2,
6.6-tetraalkyl-4-piperidinone to 4-(
1-halo 4- (N-acyl-N-alkylaju)) A series of reactions to produce -2,2,6,6-tetraalkylpiperidine are carried out in a so-called one-pot reaction without separating and purifying intermediate products. 1-halo 4-(N-acyl-N-alkyl ξ))
- Advantageous in the industrial production of 2,2,6,6 tetraalkylpiperidines.

According to the present invention, 4-(N-acyl-N-alkylamino)
- By directly adding a halogen to a solvent containing 2,2,6,6-tetraalkylpiperidine in the presence of an alkali and causing the reaction, there is no need for an excess alkali,
Moreover, the reaction is carried out at a temperature around room temperature, and the desired 1-halo 4-(N-acyl-
N-alkylamino)-2,2,6,6-titraalkylbiperidine can be advantageously obtained industrially.

Furthermore, according to the present invention, from 2,2,6,6-tetraalkyl-4-piperidinone in a so-called one-pot reaction,
1-halo 4-(N-acyl-N-alkylamino)
-2,2,6,6-tetraalkylpiperidine can be advantageously produced industrially.

Although the present invention will be explained below with reference to Examples, the present invention is not limited to these Examples in any way.

Example 1 4-(N-acetyl-N-methylamino)-2°2.6
．． 6-titramethylpiperidine 1'86.1g (0°5
50.0 g (0.6 mol) of a 48% aqueous sodium hydroxide solution was added to a mixture consisting of 247.6 g of water and 247.6 g of water to obtain a slurry. While maintaining the temperature of this slurry at 35° C., 39.1 g (0.55 mol) of chlorine was blown into it over a period of 2 hours.

After the reaction is completed, the reaction mixture is allowed to cool to room temperature, the formed crystals are centrifuged, and then re-slurried in 200 ml of water for washing, dried under reduced pressure to a constant weight, and the melting point is 90~90.
93℃, purity (according to iodometry. The same applies hereinafter)
120.3 g (yield: 97.3%) of 99.8% 1-chloro-4-(N-acetyl-N-methylamino)-2°2.6.6-titramethylbiveridine was obtained.

FIG. 1 shows the infrared absorption spectrum, FIG. 2 shows the proton nuclear magnetic resonance spectrum, and FIG. 3 shows the 1tffi analysis spectrum.

Examples 2 to 9 The reaction was carried out in the same manner as in Example 1, except that the amount of water or 48% aqueous sodium hydroxide solution used, or the reaction temperature was changed as shown in Table 1. 1-chloro-4-(N-acetyl-N-methylamino) -2,
2,6,6-titramethylpyroveridine was obtained. As in Example 1, 1-chloro-4-(
N-acetyl-N-methylamino) -2,2,6,6
The yield of -titramethylpiperidine is shown in Table 1.

Example 10 4-(N-acetyl-N-methylamino)-2°2.6
．． A mixture of 106.1 g (0.5 mol) of 6-titramethylpiveridine, 247.6 g of water and 212.2 g of methylene chloride was added with 50.0 g of a 48% aqueous sodium hydroxide solution.
g (0.6 mol) and while keeping it at 10°C,
39.1 g (0.55 mol) of chlorine was blown into this over a period of 2 hours.

After the reaction was completed, the methylene chloride layer was separated, washed with 70 ml of water, and then the methylene chloride was distilled off. The obtained residue was dried under reduced pressure to obtain 1-chloro-4-(N
-acetyl-N-methylamino)-2,2,6,6-titramethylpiveridine 122.1 g (yield 98.9.
%) was obtained.

Example 11 The reaction was carried out in the same manner as in Example 1, except that 84.2 g of a 40% potassium hydroxide aqueous solution was used in place of the 48% sodium hydroxide aqueous solution, and 1-chloro-4 -(N-acetyl N-methylamino) -2,
2,6,6-titramethylpiperidine yield 96.4%
Obtained at.

Example 12 The reaction was carried out in the same manner as in Example 1, except that 23 g of calcium hydroxide was used instead of the 48% aqueous sodium hydroxide solution, and 1-chloro-4-(N
-acetyl-N-methylamino) -2,2,6,6-
Citramethylpiperidine was obtained in a yield of 94.5%.

Example 13 In Example 1, instead of 4-(N-acetyl-N-methylamino)-2,2,6,6-titramethylbiveridine, 4-(N-acetyl-N-ethylamino)- 2
, 113.1 g of 2,6,6-titramethylbiperidine (
The reaction was carried out in the same manner as in Example 1 except that 1-chloro-4-(N-acetyl-N-
Ethylamino)-2,2,6,6-titramethylbiperidine was obtained in a yield of 98.2%.

Example 14 In Example 1, 4-(N-propionyl-N-methylamino) was used instead of 4-(N-acetyl-N-methylamino)-2,2,6,6-titramethylpiperidine.
-2,2,6,6-titramethylpiperidine 113.
The reaction was carried out in the same manner as in Example 1, except that 1 g (0.5 mol) was used, and 1-chloro-4-(N-propionyl-N-methylamino)2.2,6.6- Citramethylpiveridine was obtained in a yield of 98.0%.

Example 15 2.2,6.6-tetramethyl-4-piperidinone 77
．． 6g (0.5 mol), 40% aqueous methylamine solution 40
．． 8g (0,525 mol), 150g water and 2% platinum/
A mixture consisting of 4.1g of activated carbon was heated at a hydrogen pressure of 40kg/
The mixture was heated and stirred using col G at 70°C for 3 hours.

After the reaction was completed, the reaction mixture was allowed to cool to room temperature, and the catalyst was filtered off. The catalyst was washed with 100 ml of water, and this washing liquid was combined with the previously obtained filtrate, from which unreacted methylamine was distilled off under reduced pressure.

56.2 g of acetic anhydride was added to the resulting residue at a temperature of 35°C.
(0.55 mol) was added dropwise over a period of 2 hours.

After this, the reaction mixture was added with 48% sulfur hydroxide at a temperature of 35°C.
-100.0 g (1.2 mol) of an aqueous solution of IJ was added dropwise.

While maintaining the temperature of the resulting slurry at 35''C, 39.1 g (0.55 mol) of chlorine was blown into it over a period of 2 hours.

After the reaction was completed, the reaction mixture was allowed to cool to room temperature, and the formed crystals were centrifuged, washed by reslurry in 100 ml of water, and dried to a constant weight under reduced pressure to obtain 1.
-chloro-4-(N-acetyl-N-ethylamino)
-2,2,6,6-titramethylbiperidine 116.1
g (total yield 93.8%).

[Brief explanation of the drawings] Figures 1, 2 and 3 each show 1-chloro-4
-(N-acetyl-N-methylamino)-2,2,6,
Infrared absorption spectrum of 6-titramethylbiperidine,
These are a proton nuclear magnetic resonance spectrum and a mass spectrometry spectrum.

Claims (4)

[Claims] (1) General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R^1, R^2, R^3 and R^4 each independently represent an alkyl group having 1 to 4 carbon atoms, and R ^5 represents an alkyl group, a cycloalkyl group, or an aralkyl group, and R
^6 represents an alkyl group. ) 4-(N-acyl-N-alkylamino) represented by
A general formula characterized by adding a halogen in the presence of an alkali to a solvent containing -2,2,6,6-tetraalkylpiperidine▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R^1, 1-halo-4-(N-acyl-N- A method for producing (alkylamino)-2,2,6,6-tetraalkylpiperidine. (2) Production of 1-chloro-4-(N-acyl-N-alkylamino)-2,2,6,6-tetraalkylpiperidine according to claim 1, wherein the halogen is chlorine. Method. (3) In the solvent, there are general formulas ▲ mathematical formulas, chemical formulas, tables, etc. ) 2,2,6,6-tetraalkyl-4-piperidinone represented by hydrogen and the general formula R^5-N in the presence of a catalyst.
By reacting an organic amine represented by H_2 (in the formula, R^5 represents an alkyl group, a cycloalkyl group, or an aralkyl group), the general formula ▲mathematical formula,
There are chemical formulas, tables, etc. ▼ (In the formula, R^1, R^2, R^3, R^4 and R^5 are the same as above.) 4-(N-alkylamino)- 2, 2, 6
, 6-tetraalkylpiperidine, and then reacted with an acid anhydride represented by the general formula (R^6CO)_2O (in the formula, R^6 represents an alkyl group) to form the general formula ▲, There are chemical formulas, tables, etc. ▼ (In the formula, R^1, R^2, R^3, R^4, R^5 and R^6 are the same as above.) 4-N-( acyl-N-alkylamino)
-2,2,6,6-tetraalkylpiperidine, and then a halogen is added to a solvent containing this in the presence of an alkali ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula , R^1, R^2, R^3, R^4, R^5 and R^6 are the same as above, and X represents a halogen atom.) 1-halo-4-(N -Acyl-N-alkylamino)-2,2,6,6-tetraalkylpiperidine manufacturing method. (4) Production of 1-chloro-4-(N-acyl-N-alkylamino)-2,2,6,6-tetraalkylpiperidine according to claim 3, wherein the halogen is chlorine. Method.