JPS6284060A - Production of 2,2,6,6-tetramethyl-4-oxopiperidine - Google Patents

Abstract

PURPOSE:To reaction between acetone or its acidic condensation product and 2,2,4,4,6-pentamethyl-2,3,4,5-tetrahydropyrimidine is carried out using sulfaminic acid or its salt as a catalyst to give the titled substance of high purity in high yield. CONSTITUTION:In the production of the titled substance by reaction between acetone or its acidic-condensation product and 2,2,4,4,6-pentamethyl-2,3,4,5- tetrahydropyrimidine, a sulfaminic acid of the formula (R<1> and R<2> are H, alkyl, cycloalkyl, acyl, aryl, aralkyl) such as amidesulfonic acid, N-methylsulfaminic acid or its salt is used as a catalyst. The amount is preferably 0.01-0.2mol per mol of the acetone. The reaction conditions are preferably at 50-60 deg.C for 0.5-10hr.

Description

Detailed Description of the Invention [Industrial Application Field] The present invention provides 2.2.6.6-tetramethyl-4- which is useful as a light stabilizer for polymeric materials and as a synthetic intermediate for pharmaceuticals.
This invention relates to an improved method for producing oxopiperidine (hereinafter sometimes abbreviated as triacetonamine).

[Conventional technology]

2.2,4,4.6-pentamethyl-2.3°4.5-
Examples of methods for producing triacetonamine from tetrahydropyrimidine (hereinafter sometimes abbreviated as acetonin) include: (1) A method of reacting acetonin with a Lewis acid such as calcium chloride or zinc chloride in the presence of water (Japanese Patent Publication No. 44 -1
(Japanese Patent Publication No. 58-30308, Japanese Patent Publication No. 58-30308, Japanese Patent Publication No. 58-30308)
8-43392), etc. are known.

[Problem that the invention seeks to solve]

However, the above method (1) has a maximum yield of about 60%, and also produces many reaction by-products from the catalyst, which require complicated treatment.

In addition, although the problem with yield was solved in method However, the problem remained that the process was not progressing sufficiently.

(Means for Solving the Problems) As a result of intensive research to overcome the above problems, the present inventors discovered a method for synthesizing triacetonamine with high yield and high purity, and the present invention I was able to complete it.

That is, the present invention provides acetone or an acidic fastener of acetone and 2.2.4,4.6-pentamethyl-2,3,4,5
- by reacting with tetrahydropyrimidine 2,2,6.
In the method for producing 6-tetramethyl-4-onasopiperidine, the general formula (wherein R1 and R2 are the same or different, hydrogen, alkyl, cycloalkyl, acyl, aryl which may have a substituent or The present invention relates to a method for producing 2,2,6,6-tetramethyl-4-oxopiperidine, which is characterized by using sulfamic acid or a salt thereof as a catalyst.

To explain the symbols in general formula (1) by definition, alkyl includes methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tertiary butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, etc. stands for cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohebutyl, etc.; acyl stands for acetyl, propionyl, butyryl, benzoyl, etc.; aryl stands for phenyl, naphthyl, etc.; aralkyl stands for benzyl, phenylethyl, phenylpropyl, etc. Substituents on the aromatic ring of aryl or aralkyl include halogens such as chlorine, bromine, and iodine, alkyls as mentioned above, alkoxys such as methoxy, ethoxy, and propoxy, trichloromethyl, tribromomethyl,
Examples include trifluoromethyl such as trifluoromethyl, nitro, and amino.

In the present invention, the acidic fasteners of acetone used alone or in combination with acetone include diacetone alcohol, mesityl oxide, holone, diacetone amine, triacetone diamine, etc. Among them, especially diacetone alcohol is preferred. The amount of acetone or acidic clamping material of acetone to be used is equal to or more than the same mole relative to acetonin as the starting material. The reaction proceeds more quickly when a larger amount is used, but it is practically preferable to use 3 to 6 moles.

Examples of the sulfamic acid of general formula (1) used as a catalyst in the present invention include amidosulfonic acid, N-
Methylsulfamic acid, N-ethylsulfamic acid, N
-Propylsulfamic acid, N-isopropylsulfamic acid, N-butylsulfamic acid, N-isobutylsulfamic acid, N-tertiary butylsulfamic acid, N-
Amylsulfamic acid, N-hexylsulfamic acid,
N-hebutylsulfamic acid, N-octylsulfamic acid, N-nonylsulfamic acid, N-decylsulfamic acid, N,N-dimethylsulfamic acid, N-methyl-N-ethylsulfamic acid, N-methyl-N-propyl Sulfamic acid, N-methyl-N-butylsulfamic acid, N-methyl-N-amylsulfamic acid, N,N
-diethylsulfamic acid, N-ethyl-N-propylsulfamic acid, N-ethyl-N-butylsulfamic acid, N-ethyl-N-amylsulfamic acid, N,N-
Dipropylsulfamic acid, N-10 pyl-N-butylsulfamic acid, N-propyl-N-amylsulfamic acid, N,N-dibutylsulfamic acid, N,N-cyamylsulfamic acid, N,N-didecylsulfamic acid Acid, N,N-diethylphosphinic acid, N,N-dioctylsulfamic acid, N,N-dinonylsulfamic acid, N,N-didecylsulfamic acid, N-cyclohexylsulfamic acid, N,N-dicyclohexylsulfamic acid acid, N-phenylsulfamic acid, N, N-diphenylsulfamic acid, N-benzylsulfamic acid, N
, N-dibenzylsulfamic acid, N-phenyl-N-
Benzylsulfamic acid, N-toluidylsulfamic acid, N-methyl-N-phenylsulfamine! , N-ethyl-N-phenylsulfamic acid, N-acetyl-N
-Phenylsulfamic acid, etc. Further, as the sulfamic acid salt, the above-mentioned alkali metal salts, alkaline earth metal salts, ammonium salts, etc. of sulfamic acid can be used, and ammonium salts of sulfamic acid are preferably used.

There is no particular limitation on the amount of these catalysts to be used, and if a large amount is used, the reaction time will be shortened. However, from an economical and workability standpoint, 0.01
~0.2 mol is preferred.

Furthermore, sulfamic acid represented by general formula (I) or a salt thereof may be used in combination with conventionally known Lewis acids, protonic acids, or salts of protonic acids and ammonia or nitrogen-containing organic bases. You can also do it. Examples of Lewis acids include zinc chloride, tin chloride, aluminum chloride, iron chloride, calcium chloride, and boron trifluoride. Protonic acids include mineral acids such as hydrochloric acid, nitric acid, sulfuric acid, phosphoric acid, hydrogen fluoride, hydrogen iodide, aliphatic or aromatic sulfonic acids such as methanesulfonic acid,
Aliphatic or aromatic phosphonic acids such as benzenesulfonic acid, p-toluenesulfonic acid, naphthalenesulfonic acid, etc.Aliphatic or aromatic phosphonic acids such as methylphosphonic acid, benzylphosphonic acid, phenylphosphonic acid, etc.Aliphatic or aromatic phosphinic acids such as dimethylphosphinic acid, diethylphosphinic acid - Basic aliphatic or aromatic carboxylic acids such as diphenylphosphinic acid, such as formic acid, acetic acid, monochloroacetic acid, dichloroacetic acid, trichloroacetic acid, propionic acid, butyric acid, lauric acid, valmitic acid, stearic acid, acrylic acid , dibasic aliphatic or aromatic carboxylic acids such as methacrylic acid, cinnamic acid, naphthalene carboxylic acid, etc., such as oxalic acid, malonic acid, succinic acid, adipic acid, sebacic acid, tartaric acid, malic acid, fumaric acid, Examples include maleic acid, phthalic acid, and terephthalic acid. Examples of the ammonium salts of protonic acids include ammonium salts of mineral acids such as ammonium chloride, ammonium bromide, ammonium iodide, ammonium nitrate, and ammonium borate; and ammonium salts of organic acids such as ammonium formate, ammonium acetate, and ammonium dichloroacetate. , ammonium trichloroacetate, ammonium trifluoroacetate, ammonium malonate, ammonium benzoate, ammonium p-toluenesulfonate, and the like. Further, as the organic base that forms a salt with the protic acid, aliphatic-class amines such as methylamine, ethylamine, n-butylamine, octylamine, dodecylamine, hexamethylene diamine, etc., aliphatic secondary amines such as dimethylamine, Diethylamine, di-n-propylamine, diisobutylamine, etc., aliphatic tertiary amines such as triethylamine, alicyclic amines such as cyclohexylamine, aromatic-grade amines such as aniline, toluidine, naphthylamine, benzidine, etc., aromatic Secondary amines such as N-methylaniline, diphenylamine, etc., aromatic tertiary amines such as N,N-diethylaniline, heterocyclic bases such as pyrrolidine, piperidine, N-methyl-2-pyrrolidone, pyrazolidine, piperazine, pyridine, Picoline, indoline, quinuclidine, morpholine, N-methylmorpholine, 1,4-diazabicyclo[2.2.2
] Examples include saturated or unsaturated nitrogen-containing organic bases such as octane, triacetone amine, urea, thiourea, strong bases or weakly basic ion exchange resins.

The catalyst of the present invention can also be used in combination with magnesium chloride, sulfite, sulfites, hydrogen sulfites, pyrosulfites, phosphorus halides, sulfur halides, and the like.

During the reaction, a solvent is not particularly required, but by using an organic solvent, the reaction temperature can be controlled and the reaction can proceed smoothly. Examples of organic solvents used include hexane, toluene, xylene, heptane, cyclohexane, methylene chloride, trichloroethane, carbon tetrachloride, chloroform, ethylene chloride, chlorobenzene, tetrahydrofuran, dioxane, diethyl ether, acetonitrile, sulfolane, nitromethane, Dimethylformamide, dimethylacetamide, tetramethylurea, hexamethylphosphoric acid amide, dimethyl sulfoxide, methanol, ethanol, propatool, isopropanol, tertiary butyl alcohol, cyclohexyl alcohol, hensyl alcohol, ethylene glycol monomethyl ether, Glycol, propane-1,3
- Examples include diols.

Further, water necessary for the reaction may be added to the reaction solution in advance, or water generated from the reaction solution may be used.

As reaction conditions when carrying out the present invention, the reaction temperature is 0 to
120°C is suitable, but it is the reflux temperature of acetone.
It is preferable to carry out the reaction at a temperature of 0 to 60°C since it produces fewer by-products. The reaction time varies depending on the reaction conditions and the amount and type of catalyst used, but the reaction is usually completed in 0.5 to 10 hours.

The desired triacetone amine can be extracted from the reaction solution obtained in this way by any known method (for example, by adding water to obtain a hydrate, or by adding an acid such as hydrochloric acid, sulfuric acid, or oxalic acid). The product can be obtained by adding an excess amount of a concentrated alkaline solution such as sodium hydroxide or potassium hydroxide, removing the aqueous layer, and then distilling the product.

[Action and effect of the invention]

It has been found that the method for producing triacetone amine of the present invention, as shown in the examples below, is extremely superior to the conventional method in terms of the amount of catalyst used, reaction time, and yield, as shown in the comparative experiments below. It was.

Comparative experiment 1 Acetonin 15.4 g, anhydrous calcium chloride 5.55
g, acetone 34.9 g, and water 1.8 g are mixed under water cooling, and then reacted at 60° C. for 13 hours. After the reaction is completed, acetone is distilled off under reduced pressure, 10 ml of a 50% aqueous sodium hydroxide solution and 10 ml of toluene are added, and the aqueous layer and organic layer are separated. After extracting the aqueous layer with toluene, the extract and organic layer were combined, and after distilling off the toluene under reduced pressure, 9.8 g of pale yellow liquid triacetonamine (melting point 35-36°C after cooling) was obtained. (yield 63%).

Daegu major acetonin 15.4 g, ammonium chloride 2.68 g
After mixing 34.9 g of 1-acetone and 1.8 g of water under water cooling, the mixture was reacted at 60° C. for 13 hours. After the reaction is complete,
By performing the same process as in Comparative Experiment 1 above, 14
．． 5 g of triacetonamine (melting point 35-36 °C after cooling)
) was obtained (yield 93.6%).

As is clear from Comparative Experiment 1 above, the amount of catalyst used in the method of the present invention (for example, Example 1) is only 1/1
A small amount of 0 is required, the reaction time is less than half the time, and the yield is extremely high.

In addition, compared to Comparative Experiment 2, the method of the present invention shows no difference in yield, but the amount of catalyst used is still 1/10.
It has the advantage that only a small amount is required and the reaction time is less than half.
Furthermore, since the amount of by-products is small, it is easy to separate and purify the target product. Furthermore, it has been found that the method of the present invention has the advantage that the reaction proceeds even at low temperatures.

Therefore, compared to conventional methods, the method of the present invention can be said to be an extremely superior method for industrially producing triacetonamine, which is useful as a light stabilizer for polymeric materials and as a synthetic intermediate for pharmaceuticals.

〔Example〕

EXAMPLES Hereinafter, the present invention will be specifically explained with reference to Examples, but the present invention is not limited to these Examples in any way.

Example 1 15.4 g of acetonin, 0.49 g of sulfamic acid (amidosulfonic acid), 34.9 g of acetone, and 1.0 g of water.
After mixing 8 g under water cooling, the mixture was reacted at 60° C. for 6 hours. After the reaction is completed, acetone is distilled off under reduced pressure, and 101111111 of a 50% aqueous sodium hydroxide solution and 10 ml of toluene are added to separate an aqueous layer and an organic layer. After extracting the aqueous layer several times with toluene, the extract and organic layer were combined, the toluene was distilled off under reduced pressure, and vacuum distillation was performed to obtain 14.6 g of triacetonamine (melting point 35-36°C after cooling). was obtained (yield 9
4.0%).

Example 2 Acetonin 15.4 g, sulfamic acid 0.49 g.

After mixing 34.9 g of acetone under water cooling, the mixture is reacted at 60° C. for 6 hours. After the reaction was completed, the same treatment as in Example 1 was performed to obtain 14.6 g of pale yellow liquid triacetonamine (melting point after cooling: 35-36°C).

Example 3 15.4 g of acetonin, 34.9 g of sulfamic acid 0.491 diacetone alcohol, and 1.8 g of water are mixed under water cooling, and then reacted at 90° C. for 2 hours.

After the reaction was completed, 14.3 g of triacetonamine (melting point 3 after cooling) was obtained by carrying out the same treatment as in Example 1 above.
5-36°C) was obtained.

Example 4 Acetonin 15.4 g, sulfamic acid 0.49 g
, 17.5 g of acetone and 1.8 g of water were mixed under water cooling, and then reacted at 60° C. for 8 hours. After the reaction, 14,1 was obtained by carrying out the same treatment as in Example 1 above.
g of triacetonamine (melting point 35-36° C. after cooling) was obtained.

Example 5 15.4 g of acetonin, 0.98 g of sulfamic acid.

After mixing 34.9 g of acetonin and 1.8 g of water under water cooling, the mixture is reacted at 30° C. for 9 hours. After the reaction is completed, 14.3 is obtained by performing the same treatment as in Example 1 above.
g of triacetonamine (melting point 35-36° C. after cooling) was obtained.

Example 6 Acetonin 15.4g, ammonium sulfamate 0
．． After mixing 57 g and 34.9 g of acetone under water cooling, the mixture is reacted at 60° C. for 6 hours. After the reaction is completed, 14.2 is obtained by performing the same treatment as in Example 1 above.
g of triacetonamine (melting point 35-36° C. after cooling) was obtained.

Example 7 15.4 g of acetonin, 0.77 g of N,N-diethylsulfamic acid, and 34.9 g of acetone are mixed under water cooling, and then reacted at 60° C. for 6 hours. After the reaction was completed, the same treatment as in Example 1 was carried out to obtain 14.5
g of triacetonamine (melting point 35-36° C. after cooling) was obtained.

Example 8 Acetonin 15.4 g, N,N-diethylsulfamate ammonium 0.85 g and acetone 34,9
After mixing with water cooling, the mixture was reacted at 60°C for 6 hours.

After the reaction, 14.1 g of triacetone amine (melting point 3 after cooling) was obtained by performing the same treatment as in Example 1 above.
5-36°C) was obtained.

Claims (1)

[Claims] Acetone or an acidic condensate of acetone and 2,2,4,
In a method for producing 2,2,6,6-tetramethyl-4-oxopiperidine by reacting with 4,6-pentamethyl-2,3,4,5-tetrahydropyrimidine,
General formulas ▲ Numerical formulas, chemical formulas, tables, etc. A method for producing 2,2,6,6-tetramethyl-4-oxohyperidine, which comprises using sulfamic acid or a salt thereof as a catalyst.