JPS62129267A - Production of 2,2,6,6-tetramethyl-4-oxopiperidine - Google Patents

Abstract

PURPOSE:To advantageously obtain the titled compound in high yield and purity, by reacting acetone or an acidic condensate thereof with 2,2,4,4,6- pentamethyl-2,3,4,5-tetrahydropyrimidine in the presence of a quinone halide as a catalyst. CONSTITUTION:Acetone or an acidic condensate thereof, particularly diacetone alcohol or both are reacted with 2,2,4,4,6-pentamethyl-2,3,4,5-tetrahydropyrimidine to give 2,2,6,6-tetramethyl-4-oxopiperidine useful as an intermediate for light stabilizers of high polymer materials or medicines, etc. In the process, a quinone halide except 2,3-dichloro-1,4-naphthoquinone is used as a catalyst to industrially and advantageously obtain the aimed compound in high yield and purity using a smaller amount of the catalyst, e.g. 1/10, and in a shorter reaction time, e.g. half or less, than by a well-known method.

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.
-Regarding 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. 58-43392) are known.

[Problem that the invention seeks to solve]

However, the maximum yield of method (1) above is about 60%, and there are also many reaction by-products coming from the catalyst, so the treatment is +9. We have to take rough measures.

In addition, although the problem with the yield was solved in method (2) above, the amount of catalyst used was more than equimolar to the raw material acetonin, and the reaction would not occur unless the amount was used, which was more like a reaction raw material than a catalyst. The problem remained that sufficient progress was not being made.

[Means for solving problems]

The present inventors conducted intensive research to overcome the above-mentioned problems, and as a result, discovered a method for synthesizing tri77tonamine with high yield and high purity, and completed the present invention.

That is, the present invention provides acetone or an acidic condensate of acetone; 2. 4. 4. 6-pentamethyl-2,3
, 4,5-tetrahydropyrimidine.2.
In the method for producing 2,6.6-tetramethyl-4-oxopiperidine, a halide of quinone (however,
Excludes 2,3-dichloro-1,4-naph I quinone. )
2,2,6.6- characterized in that it uses as a catalyst
The present invention relates to a method for producing tetramethyl-4-oxopiperidine.

In the present invention, examples of the acidic condensate of acetone used alone or in combination with acetone include diacetone alcohol, mesityl oxide, holone, diacetonamine, triacetone diamine, etc. Diacetone alcohol is preferred. The amount of acetone or acidic condensate of acetone to be used is equal to or more than 7 moles per mole of acetonin as the starting material.The reaction proceeds more quickly when a large amount is used, but in practice it is 3 to 6 moles per mole of acetonin used. Preferably, moles are used.

In the present invention, quinone halides used as catalysts include chloro-p-benzoquinone, bromo-
p-benzoquinone, iodo-p-benzoquinone, dichloro-p-benzoquinone (e.g. 2,6-dichloro-
p-benzoquinone), dibromo-p-benzoquinone (e.g. 2,6-dibromo-p-benzoquinone), short-p-benzoquinone (e.g. 2,6-diiodo p-henzoquinone), trichlor-p-benzoquinone, tribromo- p-benzoquinone, triiodo-p-benzoquinone, tetrachlor-p-benzoquinone, tetrabromo-p-benzoquinone, tetraiodo-p-benzoquinone, 4-chloro-〇-henzoquinone, 4-bromo-
0-benzoquinone, 4-iodo-〇-benzoquinone, 4
．． 5-dichloro-〇-benzoquinone, 4,5-dibromo-〇-henzoquinone, 4,5-short-〇-penzoquinone, tetrachloro-〇-benzoquinone, tetrabromo-〇-benzoquinone, tetrayo, )'-o-henzoquinone, etc. benzoquinone halide, 2-chloro-
1,4-naphthoquinone, 2-bromo-1,4-naphthoquinone, 2-iodo-1,4-naphthoquinone, 2,3-dibromo-1,4-naphthoquinone, 2,3-short-1
, 4-naphthoquinone, 3-chloro-1,2-naphthoquinone, 3-promo-1,2-naphthoquinone, 3-iodo=
1.2-naphthoquinone, 4-chloro-1,2-naphthoquinone, 4-bromo-1,2-naphthoquinone, 4-iodo-12-naphthoquinone, 3.4-dichloro-1,2-naphthoquinone, 3,4- Examples include halides of naphthoquinone such as dibromo-1,2-naphthoquinone and 3,4-short-1,2-naphthoquinone, as well as halides of anthraquinone, but the catalyst used in the present invention can be produced industrially at low cost. It is advantageous to use chlorinated products, which are easy to handle.

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.

The quinone halide used in the present invention can also be used in combination with conventionally known Lewis acids, protonic acids, or salts of protonic acids and ammonia or nitrogen-containing organic bases. Here, examples of the Lewis acid include zinc chloride, tin chloride, aluminum chloride, iron chloride, calcium chloride, and boron trifluoride.

Examples of protonic acids include inorganic acids such as hydrochloric acid, nitric acid, sulfuric acid, phosphoric acid, hydrogen fluoride, hydrogen iodide, methanesulfonic acid, Hensensulfonic acid, p-toluenesulfonic acid,
Aliphatic or aromatic sulfonic acids such as naphthalenesulfonic acid, aliphatic or aromatic phosphonic acids such as methylphosphonic acid, hensylphosphonic acid, phenylphosphonic acid, aliphatic or aromatic phosphonic acids such as dimethylphosphinic acid, diethylphosphinic acid, diphenylphosphinic acid, etc. Aromatic phosphinic acid, formic acid, acetic acid, monochloroacetic acid, dichloroacetic acid,
Monobasic aliphatic or aromatic carboxylic acids such as trichloroacetic acid, propionic acid, acetic acid, lauric acid, palmitic acid, stearic acid, acrylic acid, methacrylic acid, cinnamic acid, naphthalene carboxylic acid, oxalic acid , malonic acid, succinic acid, adipic acid, sebacic acid, tartaric acid,
Examples include dibasic aliphatic or aromatic carboxylic acids such as malic acid, fumaric acid, maleic acid, phthalic acid, and terephthalic acid. In addition, the ammonium salts of protonic acids include ammonium salts of mineral acids such as ammonium chloride, ammonium bromide, ammonium iodide, ammonium nitrate, ammonium borate, ammonium formate, ammonium acetate, ammonium dichloroacetate,
Examples include ammonium salts of organic acids such as ammonium trichloroacetate, ammonium trifluoroacetate, ammonium malonate, ammonium benzoate, and ammonium p-toluenesulfonate. Furthermore, examples of organic bases that form salts with the protonic acids include aliphatic amines such as methylamine, ethylamine, n-butylamine, octylamine, dodecylamine, and hexamethylene diamine, dimethylamine, diethylamine, di-n- Aliphatic secondary amines such as propylamine and diisobutylamine, aliphatic tertiary amines such as triethylamine, alicyclic amines such as cyclohexylamine, aromatic amines such as aniline, toluidine, naphthylamine, and hengedine.
aromatic secondary amines such as N-methylaniline, diphenylamine, aromatic tertiary amines such as N,N-diethylaniline, pyrrolidine, piperidine, N-methyl-2-pyrrolidone, virapridine, piperazine, pyridine, picoline , indoline, quinuclidine, morpholine, N-methylmorpholine, 1,4-diazabicyclo[2.2.2]octane, heterocyclic bases such as triacetonamine, urea, thiourea, strong bases or weakly basic ion exchange resins, etc. Examples include saturated or unsaturated nitrogen-containing organic bases such as.

Further, the catalyst of the present invention can be used as magnesium chloride, sulfite, sulfite, hydrogen sulfite, pyrosulfite, sulfamic acid and its salts, phosphorus halides, sulfur halides,
or their oxyhalides, or beryllium, silicon, titanium, vanadium, chromium, manganese,
Cobalt, Nikkent,! Same, quersimanium, selenium, zirconium, niobium, molybdenum, cadmium, indium, antimony, tellurium, tungsten, mercury,
It can also be used in combination with a metal halide or oxyhalide selected from lead and bismuth.

During the reaction, a solvent is not particularly necessary, but the reaction temperature can be controlled by using an organic solvent. 11 L, the reaction can proceed smoothly. The seven 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, Examples include glycol, propane-1,3-diol, and the like.

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 manner by any known method, such as by adding water to obtain a hydrate, or by adding an acid such as hydrochloric acid, sulfuric acid, or oxalic acid. A method for obtaining the product as a salt, or a method for obtaining the product by adding an excess amount of an alkali solution such as sodium hydroxide or potassium hydroxide, removing the aqueous layer, and distilling the product by distillation is used.

[Action and effect of the invention]

The method for producing triacetone amine of the present invention, which is shown in the Examples below, is significantly superior to the conventional method shown in the comparative experiments below in terms of the amount of catalyst used, reaction time, and yield. was discovered.

Comparative experiment 1 Acetonin 15.4g, anhydrous calcium chloride 5.55g
, 34.9 g of acetone and 1.8 g of water were mixed under water cooling, and then reacted at 60° C. for 13 hours. After the reaction is complete,
Acetone is distilled off under reduced pressure, 10 ml of 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, the toluene was distilled off under reduced pressure, and then distillation was performed under reduced pressure to obtain 9.8 g of pale yellow liquid triacetone amine (melting point 35-36'c after cooling). was obtained (yield 63%).

Stop Calibration V↓ Complete Setonin 15.4g, Ammonium Chloride 2.68g,
After mixing 34.9 g of 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 treatment as in Comparative Experiment I above, 14
．． 5 g of triacetonamine (melting point 35-36 °C after cooling)
) was obtained (yield 93.6%).

As is clear from the above comparative experiment 1, the amount of catalyst used in the method of the present invention (for example, Example 1) is as small as 1/lO in molar ratio, and the reaction time is short, less than half, and Very high yield. Also, comparative experiment 2
Compared to the method of the present invention, there is no difference in yield, but the amount of catalyst used is still only 1/10 Kakegawa,
It has the advantage of reducing the reaction time by half or less, and 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 innovative method for industrially producing triacetonamine, which is useful as a synthetic intermediate for polymer materials such as light stabilizers and 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, 1.23 g of tetrachloro-p-benzoquinone, 34.9 g of acetone and 1.8 g of water
After mixing with water cooling, the mixture was reacted at 60°C for 6 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 1\n layer are separated. After extracting the aqueous layer several times with all 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 pale yellow liquid triacetone amine (melting point 35-35 after cooling). 36° C.) was obtained (yield 94, 2%).

Example 2 15.4 g of acetonin, 0.88 g of 2.6-dichloro-p-benzoquinone, and 34.9 g of acetone are mixed under water cooling, and then reacted at 60° C. for 6 hours.

After completion of the reaction, treatment was carried out in the same manner as in Example 1, yielding 14.1 g of triacetonamine (melting point 35-35 after 6 hours).
36°C) was obtained.

Example 3 15.4 g of acetonin, 1.33 g of 2.6-dipromo-p-henzoquinone, 34.9 g of acetone and water]
, 8g were mixed under water cooling, and then reacted at 60°C for 6 hours. After the reaction was completed, the same procedure as in Example 1 was followed to obtain 14.0 g of triacetonamine (melting point 35-36° C. after 6 hours).

Example 4 15.4 g of acetonin, 0.71 g of 4-chloro-0-henzoquinone, and 349 g of acetone are mixed under water cooling, and then reacted at 60° C. for 6 hours. After completion of the reaction, the same procedure as in Example 1 was followed to obtain 13.3 g of triacetonamine (melting point 35-36° C. after 6 hours).

Example 5 15.4 g of acetonin, 0.96 g of 2-chloro-1,4-naphthoginone, 9 g of acetonin and 1.8 g of water were mixed under water cooling, and then heated to 60°C at 60°C. Allow time to react. After the reaction was completed, the treatment was carried out in the same manner as in Example 1, yielding 13.5 g of triacetonamine (
6 melting point 35-36°C) was obtained.

Example 6 15.4 g of acetonin, 1.23 g of tetrachloro-p-henzquinone and 34.9 g of diacetone alcohol
After the reaction was completed at 90"C for 2 hours, 13.3 g of 1-lyacetonamine (melting point 3 after 6
5-36°C) was obtained.

Example 7 15.4 g of acetonin, 1.97 g of tetrachloro-p-henzoquinone and 34.9 g of acetone are mixed under water cooling, and then reacted at 30°C for 9 hours. After the reaction is complete,
When processed in the same manner as in Example 1, 12.4
g of triacetonamine (melting point 35-36° C. after 6) was obtained.

Claims (1)

[Claims] Acetone or an acidic condensate of acetone and 2,2,4,
In the method for producing 2,2,6,6-tetramethyl-4-oxopiperidine by reacting with 4,6-pentamethyl-2,3,4,5-tetrahydropyrimidine, a halide of quinone (however, 2 ,3-dichloro-1,
Excludes 4-naphthoquinone. ) as a catalyst.