DE2429937C2 - - Google Patents

Description

The preparation of 2,2,6,6-tetramethyl-4-oxopiperidine is already known. It consists of 2.2, 4,4,6-pentamethyl-2,3,4,5-tetrahydropyrimidine with a Lewis acid, preferably zinc chloride or calcium chloride reacted in the presence of water. This as a starting material Pyrimidine derivative that can be used is acetone and ammonia can be produced, its isolation from the reaction medium however, as well as possibly cleaning requires one considerable workload.

Both reaction steps have also been tried  to unite, d. H. the production of 2,2,6,6- Tetramethyl-4-oxopiperidine directly from acetone, without isolation to realize the pentamethyltetrahydropyrimidine. Attempts to this end have so far been unsuccessful Yields, reaction mixtures arise, the Separation is difficult and lossy.

It has now surprisingly been found that one in compliance with certain procedural conditions directly from acetone 2,2,6,6-tetramethyl-4-oxopiperidine in can produce good yield and purity. The procedure consists of two procedural steps, one after the other are feasible, so that it is especially for the large-scale production of tetramethylpiperidone is suitable.

The invention relates to a method for manufacturing of 2,2,6,6-tetramethylpiperidin-4-one by reacting Acetone with ammonia in the presence of acidic catalysts, characterized in that one

• a) acetone with at least 0.15 mol of ammonia per mol of acetone starting material in the presence of 0.2-12 mol percent, based on the acetone used, of the acid catalyst from the group
  • 1. an ammonium salt of a protonic acid with a pK value below 5.0 or
  • 2. the corresponding acid alone or
  • 3. Boron trifluoride or
  • 4. Boron trifluoride in a mixture with the ammonium salt according to 1. or with the acid according to 2., or
  • 5. aluminum chloride or tin tetrachloride, and optionally from 0.01-0.5 mol percent, based on the acetone used in process step a), of a cocatalyst different from this from the group potassium iodide, sodium iodide, lithium bromide, lithium iodide, lithium rhodanide, ammonium rhodanide, lithium cyanide, lithium nitrate, ammonium sulfide , Bromine, iodine or a bromide, iodide, nitrate, methanesulfonate, benzenesulfonate or p-toluenesulfonate of ammonia, triethylamine, urea or thiourea can react at temperatures of 5 to 60 ° C and then
• b) the reaction with or without the addition of further acetone completed by further heating, the total amount of the acetone used in the reaction Amount of ammonia in a molar ratio of is equal to or greater than 1.6: 1.

Examples of protonic acids or acid components in as Salts used in acidic catalysts are in particular: Mineral acids, such as hydrochloric acid, hydrobromic acid, hydroiodic acid, Nitric acid, sulfuric acid and phosphoric acid, and also sulfonic acids, such as aliphatic or aromatic sulfonic acids, e.g. B. methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid or naphthalenesulfonic acid, phosphonic acids and Phosphinic acids, such as aliphatic or aromatic, e.g. B. Methyl, benzyl or phenylphosphonic acid, or dimethyl, Diethyl or phenylphosphinic acid, and carboxylic acids, such as monobasic, dibasic or tribasic aliphatic or aromatic carboxylic acids, e.g. B. saturated or unsaturated monobasic aliphatic carboxylic acids with 1-18 C atoms, such as Formic acid, acetic acid, chloroacetic acid, dichloroacetic acid, Trichloroacetic acid, propionic acid, butyric acid, lauric acid, Palmitic acid, stearic acid, acrylic acid, methacrylic acid and Cinnamic acid, saturated and unsaturated dibasic aliphatic Carboxylic acids, such as oxalic acid, malonic acid, succinic acid, Adipic acid, sebacic acid, tartaric acid, malic acid,  Fumaric acid and maleic acid, three-base aliphatic carboxylic acids, like citric acid, monobasic aromatic carboxylic acids, such as optionally substituted benzoic acid and Naphthoic acid, and dibasic aromatic carboxylic acids, such as Phthalic acid and terephthalic acid. Monobasic are preferred and dibasic aliphatic or aromatic carboxylic acids and monobasic aromatic sulfonic acids, such as acetic acid, Succinic acid, maleic acid, benzoic acid, o-iodo-benzoic acid, m-methylbenzoic acid, p-tert-butylbenzoic acid, p-toluenesulfonic acid and cinnamic acid. To form ammonium salts Ammonia or organic bases, such as aliphatic, alicyclic and aromatic, primary, secondary and tertiary Amines, saturated and unsaturated nitrogen bases, urea, Thiourea and basic ion exchange resins. So are aliphatic primary amines, e.g. B. methylamine, ethylamine, n-butylamine, octylamine, dodecylamine and hexamethylene diamine, aliphatic secondary amines e.g. B. dimethylamine, diethylamine, Di-n-propylamine and di-isobutylamine, aliphatic tertiary Amines, e.g. B. triethylamine, alicyclic primary amines, e.g. B. Cyclohexylamine, aromatic primary amines, e.g. B. aniline, toluidine, Naphthylamine and benzidine, aromatic secondary amines, e.g. B. N-methylaniline and diphenylamine, aromatic tertiary Amines, e.g. B. N, N-diethylaniline, saturated and unsaturated Nitrogen bases, e.g. B. heterocyclic bases, e.g. B. pyrrolidine, Piperidine, N-methyl-2-pyrrolidone, pyrazolidine, piperazine, Pyridine, picoline, indoline, quinuclidine, morpholine, N-methylmorpholine, 1,4-diazabicyclo [2,2,2] octane and triacetonamine, Urea, thiourea and strong and weakly basic Ion exchange resins. Acetonine and are also preferred Diacetonamine and triacetonamine. Examples of preferred Salts are: cyclohexylamine formate, pyridine formate, pyridine p-toluenesulfonate, di-n-butylamine acetate, di-n-butylamine benzoate, Morpholine succinate, morpholine maleate, triethylamine acetate, Triethylamine succinate, triethylamine maleate, aniline acetate,  Triacetonamine p-toluenesulfonate and acetonine hydrochloride.

Ammonium chloride or boron trifluoride are particularly preferred or a mixture of both compounds.

These catalysts are used in an amount of 0.2 to 12 mol%, based on the acetone used, preferably 2-5 mol% is used.

The following can be used as additional cocatalysts: potassium iodide, Sodium iodide, lithium bromide, lithium iodide, lithium rhodanide, Ammonium rhodanide, lithium cyanide, lithium nitrate, ammonium sulfide, Bromine, iodine, or a bromide, iodide, nitrate, methanesulfonate, Benzenesulfonate or p-toluenesulfonate of ammonia, triethylamine, Urea or thiourea, for example in Amounts of 0.01 to 0.5 mol% based on acetone.

The reaction temperature is in the first stage of the process 5 to 60 ° C, preferably 5 to 35, particularly preferably 5 to 25 ° C. The first proves advantageous Process stage of adding a mono- or polyfunctional Alcohol. Examples of suitable alcohols are Methanol, butanol, cyclohexanol, benzyl alcohol, ethylene glycol monoethyl ether or 2-ethylhexanol. Preferably used low monoalcohols such as methanol, ethanol and isopropanol, of which the methanol is particularly preferred.

The response time of this first, at lower Process temperature is at least 1, preferably 3 hours.

Process variants are the following:

• 1. The method, characterized in that the acetone in process step a) partly by diacetone alcohol and / or mesityl oxide is replaced.  
• 2. The method, characterized in that the acetone in process step b) partially or completely by diacetone alcohol and / or mesityl oxide is replaced.
• 3. The method, characterized in that the reaction under Pressure is carried out, in which case a reaction temperature of over 60 ° C is possible.

The isolation of the tetramethylpiperidone can be done in done in a known manner, for. B. by adding Water and separation as hydrate, or by adding acid, such as hydrochloric acid, sulfuric acid or oxalic acid and separation as salt, or by adding an excess of lye, especially concentrated lye, such as aqueous sodium hydroxide solution or potassium hydroxide solution and separation as an organic layer, or in particular by distillation, if appropriate after neutralization the catalyst by adding base, such as sodium hydroxide, Potassium hydroxide or sodium carbonate.

The one used in the first stage of the process To some extent, acetone can contain water and / or condensation products of acetone, such as diacetone alcohol, mesityl oxide,  Contain phoron, diacetonamine and / or triacetone diamine. A such addition can have a favorable effect on the yield. A preferred condensation product of the acetone is mesityl oxide and especially diacetone alcohol. This makes it possible this is done by distillation at the end of the second stage use distillate as raw material in the first stage, which results in high acetone turnover. Increases the water content of the reaction medium z. B. in such Recycle too much, so it is recommended to part to remove the water from the reaction mixture. This can for example, that at the end of the first Stage of the reaction mixture concentrated alkali, e.g. sodium hydroxide solution, adds and after briefly stirring the aqueous Separates the layer.

In the method according to the invention can also organic solvents can be used.

Organic solvents for the inventive method are particularly suitable, for. B. hydrocarbons, such as aromatics, e.g. B. benzene, toluene and xylene, and aliphates, such as hexane, heptane and cyclohexane, as well as chlorinated hydrocarbons, such as methylene chloride, trichloroethane, carbon tetrachloride, Chloroform, ethylene chloride and chlorobenzene, and ether, such as Tetrahydrofuran, dioxane and diethyl ether, and nitriles, such as Acetonitrile, and aprotic polar solvents, such as sulfolane, Acetonitrile nitromethane, dimethylformamide, dimethylacetamide, Tetramethyl urea, hexamethyl phosphoric acid amide and dimethyl sulfoxide, and particularly preferably alcohols, such as mono- or polyfunctional, unsubstituted or substituted aliphatic Alcohols, e.g. B. lower alkanols, such as methanol, ethanol, propanol, iso-propanol and tert-butanol, as well as cyclohexanol, benzyl alcohol, Ethylene glycol monomethyl ether, glycol and propane-1,3-diol,  especially a C₁-C₄ alcohol, such as methanol, and diacetone alcohol, Phoron, diacetonamine, triacetone diamine and mesityl oxide. Mixtures of the above solvents are also suitable.

The present invention is accomplished by the following Illustrated examples. Further advantageous configurations of the method according to the invention are from the claims to see.  

example 1

A suspension consisting of 11 g ammonium chloride and a mixture of 340 g acetone and 64 g methanol saturated with ammonia gas for 12 hours at 13 to 17 ° C. Then the resulting colorless oil with 350 g Dilute acetone and stir for 15 to 20 hours Kept at 50-55 ° C. Excess solvent is then removed by evaporation in a vacuum and displaces the reddish one Residue with 36 g of water. The one that starts at 0 to 5 ° C Crystallization is completed by stirring for 2 hours. 286 g of 2,2,6,6-tetramethyl-4-oxopiperidine are obtained. Hydrate of mp, 55-60 ° C in the form of a slightly yellowish color Crystals.

The product is obtained as the oxalate salt from the decomposition point 180 ° C if you use the reaction mixture Neutralized oxalic acid.

Example 2

The procedure is as given in Example 1, with the difference that in the 2nd step together with the addition of acetone 1.3 g of boron fluoride, dissolved in ether, added becomes. Isolation of 2,2,6,6-tetramethyl-4-oxopiperidine takes place as described in Example 1.  

Example 3

The procedure is as in Example 1, with the difference that that instead of ammonium chloride 1.3 g boron trifluoride, can be used dissolved in ether. In the second step then 11 g of ammonium chloride together with the Acetone was added to the reaction mixture.

Examples 4-7

A suspension consisting of 11 g ammonium chloride, 340 g of acetone and 64 g of methanol is used for 4 hours saturated at 13 to 17 ° C with ammonia gas. Subsequently the resulting colorless oil is diluted with 900 g of acetone and kept at 50-55 ° C with stirring for 15 to 20 hours. To The first 6 hours becomes a solution within 1-2 hours 70 g of 97% sulfuric acid added dropwise. At the end of the response time the pH of the reaction mixture with 97% Sulfuric acid to the value 4.5 to 5 within 1-2 hours posed. The resulting suspension of hydrosulfate from 2,2,6,6-Teetramethyl-4-oxopiperidine is filtered at 5-10 ° C and washed with acetone. 655 g of hydrosulfate Salt, which corresponds to 381 g of 2,2,6,6-tetramethyl-4-oxopiperidine.

Proceed as described above, but in 2nd step the amount of acetone and specified in Table 1 Sulfuric acid used, so you get the one in the third Column of the yields given in the table.  

Example 8

A suspension consisting of 11 g ammonium chloride, 340 g of acetone and 64 g of methanol is used for 4 hours saturated at 13 to 17 ° C with ammonia gas. Subsequently the resulting colorless oil is diluted with 900 g of acetone and kept at 50-55 ° C with stirring for 15 to 20 hours. To The pH of the solution is initiated during the first 6 hours from about 23 g of hydrogen chloride gas to 8.5-8.6. At the end of the reaction time the pH of the reaction mixture with hydrogen chloride within 1-2 hours Value 5 to 6 set. The resulting hydrochloride suspension of 2,2,6,6-tetramethyl-4-oxopiperidine is used in Filtered 0-5 ° C and washed with acetone. You get 400 g of hydrochloride salt, which contains 293 g of 2,2,6,6-tetramethyl  4-oxopiperidine corresponds.

After distilling off the mother liquor H₂O and methanol and dilution of the distillation residue with acetone a further 95 g of hydrochloride, which contains 70 g of 2,2,6,6- Tetramethyl-4-oxopiperidine corresponds, isolated.

Example 9

In a mixture consisting of 126 g acetone, 22.5 g Methanol and 4.7 g of ammonium chloride become 40 g of ammonia gas initiated in about 4 hours at 13-15 ° C. The reaction mixture is then 30 minutes at the same temperature touched. Then add 220 g of diacetone alcohol and 110 g acetone to the reaction mixture, warmed the whole inside 1 hour at 55 ° C and it stays there for 12 hours Temperature. Working up the experiment by fractional Distillation gives 125 g of 2,2,6,6-tetramethyl-4-oxopiperidine.  

Example 10

A suspension consisting of 11 g ammonium chloride, 340 g of acetone and 64 g of methanol is used for 4 hours saturated at 13 to 17 ° C with ammonia gas. Subsequently the resulting colorless oil is diluted with 900 g of acetone and kept at 50-55 ° C with stirring for 15 to 20 hours.

The resulting reaction mixture contains according to Gas chromatogram 378 g of 2,2,6,6-tetramethyl-4-oxopiperidine (Triacetonamine), which is isolated by distillation.

Example 11

A suspension of 11 g ammonium chloride, 340 g Acetone and 4 g of 20% aqueous solution of ammonium sulfide saturated with ammonia gas for 4 hours at 13 to 17 ° C. Then continue as indicated in Example 10.

The reaction mixture finally contains 450 g of triacetonamine.

Example 12

A suspension of 11 g ammonium chloride, 340 g Acetone and 1 g of potassium iodide are mixed with ammonia gas for 4 hours saturated. Then continue as in Example 10 is specified. The reaction mixture contains 400 g triacetonamine.  

Example 13

The same procedure as in Example 10 is followed, however 64 g of dioxane are used instead of 64 g of methanol.

The reaction mixture contains 314 g of triacetonamine.

Example 14

The same procedure as in Example 10 is followed, however 64 g of ethanol are used instead of 64 g of methanol.

The reaction mixture contains 363 g of triacetonamine.

Example 15

The same procedure as in Example 10 is followed, however 64 g of isopropanol are used instead of 64 g of methanol.

The reaction mixture contains 350 g of triacetonamine.

Example 16

The same result as in Example 15 is obtained when the methanol through 64 g of dimethylformamide replaced.  

Example 17

The same procedure as in Example 10 is followed, however without added methanol.

The reaction mixture contains 336 g of triacetonamine.

Example 18

A suspension consisting of 11 g ammonium chloride, 340 g of acetone and 64 g of methanol is used for 4 hours saturated at 13 to 17 ° C with ammonia gas.

Then the resulting colorless oil diluted with 1360 g acetone and with stirring for 15-20 hours kept at 50-55 ° C.

The resulting reaction mixture contains 420 g Triacetonamine.

Example 19

The same procedure as in Example 10 is followed, however is after dilution with 900 g of acetone initially 6 hours at 50-55 ° C and then 3 hours under strong reflux (at 56-60 ° C) stirred.

The resulting reaction mixture contains 337 g Triacetonamine.  

Example 20

The same procedure as in Example 10 is followed, however instead of 11 g of ammonium chloride 5.5 g and 38 g Ammonium chloride used:

Ammonium chloride triacetonamine gim reaction mixture

5.5220 38381

Claims (4)

1. A process for the preparation of 2,2,6,6-tetramethyl-piperidin-4-one by reacting acetone with ammonia in the presence of acidic catalysts, characterized in that

• a) acetone with at least 0.15 mol of ammonia per mol of acetone starting material in the presence of 0.2-12 mol percent, based on the acetone used, of the acid catalyst from the group
  • 1. an ammonium salt of a protonic acid with a pK value below 5.0 or
  • 2. the corresponding acid alone or
  • 3. Boron trifluoride or
  • 4. Boron trifluoride in a mixture with the ammonium salt according to 1. or with the acid according to 2. or
  • 5. aluminum chloride or tin tetrachloride, and optionally from 0.01-0.5 mol percent, based on acetone used in process step a), of a cocatalyst different from this from the group potassium iodide, sodium iodide, lithium bromide, lithium iodide, lithium rhodanide, ammonium rhodanide, lithium cyanide, lithium nitrate, ammonium sulfide , Bromine, iodine or a bromide, iodide, nitrate, methanesulfonate, benzenesulfonate or p-toluenesulfonate of ammonia, triethylamine, urea or thiourea can react at temperatures of 5 to 60 ° C and then
• b) the reaction with or without the addition of further acetone is completed by further heating, the total amount of acetone used in the reaction being equal to or greater than 1.6: 1 to the amount of ammonia used.

2. The method according to claim 1, characterized in that the acetone in process step a) partly by diacetone alcohol  and / or mesityl oxide is replaced. 3. The method according to claim 1, characterized in that the Acetone in process step b) partially or completely by diacetone alcohol and / or mesityl oxide is replaced. 4. The method according to claims 1 to 3, characterized in that the reaction is carried out under pressure, in which case a reaction temperature of over 60 ° C is possible.