JPH0395163A - Production of 2,2,4,4,6-pentamethyl-2,3,4,5-tetrahydropyrimidine - Google Patents

Abstract

PURPOSE:To obtain the subject compound as a stabilizer for synthetic polymer materials or intermediate for medicines, etc., in high yield for a short time without using a corrosion-resistant material and forming by-products by reacting acetone with ammonia using an iron carboxylate catalyst. CONSTITUTION:Acetone and/or an acidic condensate thereof and ammonia are reacted in the presence of an iron carboxylate catalyst in an amount of 0.05-10mol%, preferably 0.1-10mol% based on the acetone and/or acidic condensate thereof at 0-60 deg.C, preferably 10-25 deg.C to afford the objective compound. Furthermore, acetic acid, lactic acid, oxalic acid, citric acid, etc., are preferred as the aforementioned carboxylic acid. Diacetone alcohol, mesityl oxide, etc., are cited as the acetone or acidic condensate of the acetone used with the acetone in combination.

Description

DETAILED DESCRIPTION OF THE INVENTION [Prior Art] The present invention involves reacting acetone and ammonia in the presence of an iron carboxylate catalyst. 2. 4. 4.6-pentamethyl-2. 3. 4. This invention relates to a method for producing 5-tetrahydropyrimidine (hereinafter referred to as acetonin).

Conventionally, as a method for producing acetonin, the method described in the Journal of the φ Chemical Society (J.C.H.) 19
47, p. 1394, or Helv.Chim.Acta, vol. 30, 19
47, p. 1114, describes a method for producing acetonin by reacting acetone and ammonia in the presence of an ammonium halide catalyst.

The above-mentioned report also discloses that the yield can be improved by using calcium chloride, calcium bromide, calcium iodide, lithium chloride, lithium bromide, etc. as co-catalysts in this reaction.

(Problems to be Solved by the Invention) However, in the above-mentioned known methods, the reaction rate in the presence of only ammonium halide is slow, and more than ten hours are required to obtain a high yield.

In addition, in reactions in the presence of calcium salts, the calcium salts form viscous lumps during the reaction, stick to the walls of the reaction tank, and impede heat transfer, resulting in poor thermal efficiency.To prevent this, strong stirring is required. Requires equipment.

Furthermore, there was a problem in that complicated measures had to be taken to treat the reaction residue containing calcium salts.

As an improvement method of the above-mentioned known method,
No. 97 discloses that the co-catalysts are bromine, iodine, iodine trichloride, ammonium iodide, alkali metal iodides, and carbon atoms of 1 to 1.
By using it in place of hydrogen iodide salts of aliphatic amines having two atoms, rhodanides, bromides or nitrates of lithium or ammonium cations, lithium cyanide, ammonium sulfides, carboxylic acids, sulfonic acids and their ammonium salts, It is disclosed that the above problems can be solved.

However, all of these systems use a halide as the main catalyst and a halide co-catalyst, and must be equipped with corrosion-resistant materials such as nickel or nickel alloy, or glass-lined equipment. However, there remained the unavoidable disadvantage in terms of equipment costs.

[Object of the invention] The object of the present invention is to provide a method for producing acetonin, which is a raw material for triacetonamine derivatives useful as synthetic polymer material stabilizers and intermediates for pharmaceuticals. The purpose of this is to produce acetonin in a short reaction time, in a good yield, without spoiling the reaction operation or in the form of substances, and without containing halogens, that is, without requiring corrosion-resistant materials. Our goal is to provide an industrial method that does not.

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

That is, the present invention provides ``an iron carboxylate containing acetone and/or an acidic condensate of acetone and ammonia in an amount of 0.05 to 10 mol% based on the acetone and/or the acidic condensate of acetone used. React in the presence of a catalyst 2.2.
4.4.6-Pentamethyl-2.3.4.5-tetrahydride-pyrimidine"

The key point of the present invention lies in the use of iron carboxylic acid, which is industrially produced at low cost and easy to handle, as a catalyst.

Examples of acetone used in the method of the present invention or acidic condensates of acetone used in combination with acetone include diacetone alcohol, mesityl oxide, holone, diacetone amine, and the like.

The catalyst used in the process of the invention is a carboxylic acid salt of iron, and the carboxylic acids used to form such a salt include mono-, di- and tri-basic aliphatic acids. and aromatic carboxylic acids.

For example, preferably saturated or unsaturated monobasic aliphatic carboxylic acids having 1 to 18 carbon atoms, such as formic acid, acetic acid, propionic acid, butyric acid, lauric acid, valmitic acid,
Stearic acid, lactic acid, acrylic acid and methacrylic acid, preferably saturated or unsaturated dibasic aliphatic carboxylic acids having 2 to 12 carbon atoms, such as oxalic acid, malonic acid, succinic acid, adivic acid, sebacic acid, tartaric acid , malic acid, fumaric acid, maleic acid, tribasic aliphatic carboxylic acids such as citric acid; optionally substituted monobasic aromatic carboxylic acids such as benzoic acid, triylic acid, cinnamic acid, naphthoic acid, Dibasic aromatic carboxylic acids, such as phthalic acid and terephthalic acid, and tribasic aromatic carboxylic acids, such as trimellitic acid.

Among these, particularly preferred carboxylic acids are acetic acid, lactic acid, oxalic acid, and citric acid.

It is possible to use normal salts, acidic salts, basic salts, and even hydrates of these salts.

Further, these catalysts can be used alone or in combination.

The amount of these catalysts used is 0.05 to 10 mol% based on acetone and/or acidic condensate of acetone.
, preferably 0. It is 1 to 5 mol%, more preferably 0.1 to 1.0 mol%.

Furthermore, the catalyst of the present invention can be used in combination with conventionally known Lewis acids, protonic acids, or salts of protonic acids and ammonia or nitrogen-containing organic bases.

Examples of Lewis acids include zinc chloride, tin chloride, aluminum chloride, iron chloride, calcium chloride, potassium iodide, sodium iodide, lithium iodide, and boron trifluoride.

Examples of protonic acids include inorganic acids such as hydrochloric acid, nitric acid, sulfuric acid, phosphoric acid, hydrogen fluoride, and hydrogen iodide; aliphatic or aromatic sulfonic acids such as methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, and naphthalenesulfonic acid. acids, aliphatic or aromatic phosphonic acids such as methylphosphonic acid, penzylphosphonic acid, phenylphosphonic acid, aliphatic or aromatic phosphinic acids such as dimethylphosphinic acid, diethylphosphinic acid, diphenylphosphinic acid, formic acid, acetic acid, monochloroacetic acid , dichloroacetic acid, propionic acid, acetic acid, lauric acid, balmitic acid, stearic acid, , lactic acid, acrylic acid, methacrylic acid, benzoic acid, cinnamic acid, naphthoic acid, monobasic aliphatic or aromatic carboxylic acid,
Oxalic acid, malonic acid, succinic acid, adipic acid, sebacic acid,
tartaric acid, malic acid, fumaric acid, maleic acid, phthalic acid,
Examples include dibasic aliphatic or aromatic carboxylic acids such as terephthalic acid, and tribasic aliphatic or aromatic carboxylic acids such as citric acid and trimellitic acid.

In addition, ammonium salts of the protonic acids include ammonium chloride, ammonium bromide, ammonium iodide,
Ammonium salts of inorganic acids such as ammonium nitrate and ammonium borate, ammonium formate, ammonium acetate, ammonium dichloroacetate, ammonium trichloroacetate, ammonium trifluoroacetate, ammonium propionate, ammonium oxalate, ammonium malonate, ammonium benzoate, p-} Examples include ammonium salts of organic acids such as ammonium luenesulfonate.

Furthermore, the organic bases forming the proton acid salts include methylamine, ethylamine, N-butylamine,
Aliphatic primary amines such as octylamine, dodecylamine, hexamethylene diamine, aliphatic secondary amines such as dimethylamine, diethylamine, di-n-propylamine, diisobutylamine, aliphatic tertiary amines such as triethylamine, cyclohexylamine, etc. alicyclic primary amines, aromatic primary amines such as aniline, toluidine, naphthylamine, benzidine, aromatic secondary amines such as N-methylaniline, diphenylamine, N-N
- Aromatic tertiary amines such as diethylaniline, pyrrolidine, piperidine, N-methyl-2-pyrrolidone, pyrazolidine, piperazine, pyridine, picoline, indoline,
Heterocyclic bases such as quinuclidine, morpholine, N-methylmorpholine, triacetonamine, urea, thiourea,
Examples include saturated or unsaturated nitrogen-containing organic bases such as strong bases or weakly basic ion exchange resins.

When using them together, it is important to avoid halides that may affect the device materials.

In carrying out the present invention, a solvent is not particularly required during the reaction, but the reaction can proceed smoothly by using an organic solvent.

The organic solvents used include pentane, heptane, hexane, benzene, toluene, cyclohexane, methylene chloride, chloroform, carbon tetrachloride tetrahydrofuran, diethyl ether, dioxane, methyl cellosolve, cellosolve, methyl propanol, dimethyl formamide, methanol, Examples include ethanol, propanol, isopropanol, butanol, t-butanol, cyclohexanol, benzyl alcohol, ethylene glycol, diethylene glycol, propylene glycol, but preferably methanol, ethanol,
Lower monohydric alcohols such as probanol and isopropanol, more preferably methanol.

As reaction conditions when carrying out the present invention, the reaction temperature is 0 to
60°C is appropriate, but in view of the solubility of ammonia or temperature control, the temperature is preferably 5 to 35°C, more preferably 10°C.
It is best to carry out at a temperature of ~25°C.

Ammonia gas is passed in calculated (stoichiometric!) or saturation amount until the end of the reaction.

The reaction time varies depending on the reaction conditions and the amount and type of catalyst used, but is usually 5 to 10 hours.

Further, the reaction may be carried out at normal pressure or under increased pressure. In this reaction, even if the catalyst is insoluble in the reaction solution, the amount of catalyst is extremely small, so no lumps are formed during the reaction, and the reaction operation is extremely easy.

After the reaction is completed, the catalyst is filtered off and the obtained catalyst is subjected to the reaction again.

On the other hand, acetonin is collected from the reaction mixture (liquid a) by a conventional method. For example, acetonin can be easily collected by adding an alkaline aqueous solution such as sodium hydroxide to the reaction mixture (filtrate) and separating and removing the aqueous layer.

[Actions and Effects of the Invention] When acetonin is produced by the method of the present invention, the highest yield of acetonin can be obtained in a shorter reaction time in the presence of a smaller amount of catalyst than in the conventional method, and the catalyst can be reused. Furthermore, depending on the selection of the solvent and the catalyst used in combination, it has advantages such as not containing a halide, which is advantageous in terms of equipment and equipment.

[Examples] Hereinafter, the present invention will be specifically explained using Examples and Comparative Examples, but these are not intended to limit the present invention in any way.

Furthermore, in the Examples and Comparative Examples, the concentration of acetonin was determined by gas chromatography.

Example-1 A flask equipped with a thermometer, reflux condenser, stirrer, and blowing tube was charged with 348 g of acetone, 3,0 g of iron acetate, and 102.8 g of ammonia gas was absorbed over 10 hours at a reaction temperature of 10 to 20°C. I let it happen.

After the reaction was completed, the amount was determined by gas chromatography.

The quantitative value of acetonin was 283.9 g, and an acetonin yield of 92.2% was obtained.

Table 1 summarizes some of the conditions and the results obtained.

Example 2 The same procedure as Example 1 was carried out except that 1.5 g of iron acetate was charged, and the results shown in Table 1 were obtained.

Example 3 The same procedure as Example 1 was carried out except that 175 g of methanol was present, and the results shown in Table 1 were obtained.

Example 4 The same procedure as Example 1 was carried out except that 1.5 g of iron acetate was changed to 3.0 g of ferrous lactate, and the results shown in Table 1 were obtained.

Example 5 The same procedure as Example 1 was carried out except that 1.5 g of iron acetate was changed to 3.0 g of iron citrate, and the results shown in Table 1 were obtained.

Example 6 Using the catalyst recovered from the reaction mixture of Example 1, a reaction was carried out under the same conditions as in Example 1, and the results shown in Table 1 were obtained.

Example 7 The same procedure as Example 1 was carried out except that 225 g of an acidic condensate of acetone was allowed to coexist, and the results shown in Table 1 were obtained.

Comparative Example 1 The same procedure as in Example 1 was carried out except that 1.5 g of iron acetate was changed to 15 g of ammonium chloride, and the results shown in Table 1 were obtained.

Comparative Example 2 The same procedure as Comparative Example 1 was carried out except that 80 g of methanol was allowed to coexist, and the results shown in Table 1 were obtained.

(Margin below)

Claims (1)

[Claims] Reacting acetone and/or an acidic condensate of acetone with ammonia in the presence of an iron carboxylate catalyst in an amount of 0.05 to 10 mol%, based on the acetone and/or the acidic condensate of acetone used. te2,2,4
, 4,6-pentamethyl-2,3,4,5-tetrahydropyrimidine.