JPH08259516A - Production of t-amine n-oxide - Google Patents

Abstract

PURPOSE: To obtain a tertiary amine N-oxide useful as an intermediate for pharmaceuticals and agrochemicals in an extremely high yield in an easily separable state by using oxide of silicon and titanium as the catalyst. CONSTITUTION: The objective oxide (preferably pyridine N-oxides or pyrazine N-oxides) is produced by reacting (A) a t-amine (preferably pyridines or pyrazines) with (B) a peroxide (preferably hydrogen peroxide) in the presence of (C) a catalyst composed of oxide of silicon and titanium. The component C is preferably a mixture of silicon oxide and titanium oxide, an amorphous titanosilicate or a crystalline titanosilicate, especially a crystalline titanosilicate having an Si/Ti atomic ratio of 10-200.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for producing a tertiary amine N-oxide. More specifically, it relates to a method for producing a tertiary amine N-oxide by reacting a tertiary amine with a peroxide in the presence of a catalyst. In the method of the present invention, for example, when pyridines or pyrazines are used as the tertiary amine as a raw material, pyridine N-oxides or pyrazine N-oxides can be produced, respectively. These pyridine N-oxides and pyrazine N-oxides are compounds useful as intermediates for medicines and agricultural chemicals.

[0002]

2. Description of the Related Art Conventionally, for example, the following method is known as a method for producing a tertiary amine N-oxide. Pyrazine N
-The conventional method will be described in detail by taking a method for producing oxides as an example. A method for producing pyrazine N-oxides by treating pyrazines with hydrogen peroxide in acetic acid (J. Org.
Chem. , 23, 1603 (1958)), a method of reacting pyrazines with hydrogen peroxide in a water solvent using sodium tungstate as a catalyst (Chem. Phar.
m. Bull. , 22, 2097 (1974)), and a method of reacting pyrazines with hydrogen peroxide in a water solvent using molybdenum trioxide as a catalyst (Japanese Patent Laid-Open No. 62-62-62).
No. 181268) is known.

[0003]

However, the above-mentioned conventional method has the following problems. The method of (1) requires the use of a large amount of acetic acid as a solvent, and has a drawback that a complicated step is required for the separation and recovery of pyrazine N-oxides and acetic acid.
And low. On the other hand, in the method (1), the target product is obtained in high yield. However, the catalyst used in the method, like the catalyst used in the method of, because it can not be easily separated from the reaction solution by dissolving in the reaction solution, as a method for isolating and purifying the target product, If the method of distilling the solvent from the reaction solution after the reaction and then recrystallizing the obtained residue is adopted, there is a problem that the catalyst is mixed with the intended product. An object of the present invention is to provide a method for producing a tertiary amine N-oxide capable of solving the above-mentioned problems of the conventional method.

[0004]

Means for Solving the Problems In the method for producing a tertiary amine N-oxide by reacting a tertiary amine with a peroxide, the present inventors have proposed a method such as filtration from the reaction solution after completion of the reaction. Various heterogeneous catalysts that can be separated by simple operation were studied. As a result, it was found that a tertiary amine N-oxide can be produced in an extremely high yield by reacting a tertiary amine with a peroxide using a catalyst composed of oxides of silicon and titanium as a catalyst. completed.

That is, the present invention relates to a method for producing a tertiary amine N-oxide, which comprises reacting a tertiary amine with a peroxide in the presence of a catalyst composed of oxides of silicon and titanium.

According to the present invention, the tertiary amine N-oxide can be obtained in an extremely high yield. Further, since the catalyst of the present invention is substantially insoluble in the reaction liquid, it can be easily separated from the reaction liquid after the reaction by filtration or the like, and the tertiary amine N-
It is not mixed in the oxide product.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION A catalyst comprising an oxide of silicon and titanium according to the present invention is a conventionally known tertiary amine, which is a method for producing a tertiary amine N-oxide, and a peroxide such as hydrogen peroxide. It can be used as a catalyst for reaction.

Examples of the tertiary amine applicable to the method of the present invention include nitrogen-containing heteroaromatic compounds, non-aromatic cyclic tertiary amines, trialkylamines and trialkenylamines.

Examples of the nitrogen-containing heteroaromatic compound include (1) pyridine, 2-methylpyridine, 3-methylpyridine, 4-methylpyridine, 2,3-dimethylpyridine, 2,4-dimethylpyridine, 3, Pyridine bases such as 5-dimethylpyridine and 2,4,6-trimethylpyridine, 2-cyanopyridine, 3-cyanopyridine, 4
-Cyanopyridines such as cyanopyridine, pyridinecarboxylic acids such as 2-pyridinecarboxylic acid, 3-pyridinecarboxylic acid and 4-pyridinecarboxylic acid, and hydrogen atoms of the pyridine nucleus of the above pyridine bases, cyanopyridines and pyridinecarboxylic acids , One or more of which are substituted with a chlorine atom, such as pyridines, (2) pyrazine, 2-methylpyrazine, 2,3-dimethylpyrazine, alkylpyrazine such as 2,5-dimethylpyrazine, and 2-cyano. Pyrazine, 2-cyano-3-methylpyrazine, 2-cyano-5
-Cyanopyrazines such as methylpyrazine, 2-pyrazinecarboxylic acid, 3-methyl-2-pyrazinecarboxylic acid, 5
-Pyrazinecarboxylic acids such as methyl-2-pyrazinecarboxylic acid and pyrazines such as pyrazines in which one or more hydrogen atoms of the pyrazine nucleus of the above pyrazine, alkylpyrazine, cyanopyrazine, pyrazinecarboxylic acid are substituted with chlorine atom (3) Quinoline, 2-methylquinoline, 4
Examples thereof include quinolines such as -methylquinoline, 2-ethylquinoline and 4-ethylquinoline.

Examples of the non-aromatic cyclic tertiary amine include (1) N-substituted morpholines such as N-alkylmorpholine and N-alkylmorpholine, and (2) N-methylpyrrolidine. Examples thereof include N-substituted pyrrolidines such as N-alkylpyrrolidine such as N-ethylpyrrolidine.

Examples of trialkylamines include triethylamine, tripropylamine, tributylamine, trioctylamine, tridecylamine, trilaurylamine and tricetylamine, and examples of trialkenylamines include triallylamine. Can be mentioned.

The pyridine N-oxides or pyrazine N-oxides obtained when pyridines or pyrazines are used as the tertiary amine are useful as intermediates for medicines and agricultural chemicals.

In the present invention, a catalyst composed of oxides of silicon and titanium is used. In the present invention, the catalyst composed of oxides of silicon and titanium is a catalyst containing silicon oxide and titanium oxide as a chemical composition or compound.

Specific examples of the catalyst composed of oxides of silicon and titanium of the present invention include a mixture of silicon oxide and titanium oxide (for example, a mixture of silicon dioxide and titanium dioxide). Other specific examples of the catalyst of the present invention include silicon-titanium composite oxides such as amorphous titanosilicate (for example, silica-titania) and crystalline titanosilicate. A crystalline titanosilicate is preferable, and a crystalline titanosilicate synthesized by a hydrothermal synthesis method is more preferable. Examples of the crystalline titanosilicate include titanosilicate TS-1 having an MFI structure and titanosilicate TS-2 having an MEL structure. These can also be obtained as commercial products.

The ratio of silicon to titanium in the catalyst composed of oxides of silicon and titanium of the present invention is usually Si / Ti.
= 10 to 200 (atomic ratio).

The catalyst of the present invention composed of oxides of silicon and titanium can be prepared by various conventionally known methods such as coprecipitation method, impregnation method, immersion method, ion exchange method and hydrothermal synthesis method. As the silicon oxide source used in preparing the catalyst,
Examples thereof include colloidal silica, silicates of alkali metals such as sodium silicate and potassium silicate, and tetraalkoxysilanes such as tetramethylorthosilicate and tetraethylorthosilicate. Examples of the titanium oxide source include tetraalkoxytitanium such as TiCl ₄ , TiOCl ₂ , tetraethyl titanate and tetraisopropyl titanate.

In the present invention, the catalyst composed of oxides of silicon and titanium can be used in various forms such as tablets, spheres, granules, powders, columns, nets, and cylinders, preferably powders. To do.

The amount of the catalyst composed of oxides of silicon and titanium used is preferably 0.1 to 5% by weight based on the tertiary amine.

A representative example of a peroxide is hydrogen peroxide, although other peroxides may be used in the present invention. The present invention will be described below by taking hydrogen peroxide as an example of peroxide. As hydrogen peroxide, an aqueous solution of 30 to 35% by weight, which is easily available as a commercial product, can be preferably used. The amount of hydrogen peroxide used is appropriately 1 to 2 times the theoretical amount with respect to 1 mol of the tertiary amine.

However, a nitrogen-containing heteroaromatic compound having two nitrogen atoms as ring-constituting atoms, such as pyrazines, is used as the starting tertiary amine, and the pyrazine ring has
In order to preferentially convert only one of the nitrogen atoms into N-oxide, the amount of hydrogen peroxide used is preferably 0.4 to 1 mol with respect to 1 mol of the pyrazines.

The method of the present invention is preferably carried out in a solvent. As the solvent, a solvent that dissolves at least a part of the tertiary amine as a raw material, does not dissolve the target substance to dissolve the catalyst in the present invention, and does not participate in the reaction can be used. As a specific example of the solvent, water, a mixture of water and an alcohol such as methanol or ethanol, and the like are preferably used, but any solvent having the above properties may be used. The amount of the solvent used is not particularly limited, but 1 to 10 parts by weight is suitable for 1 part by weight of the tertiary amine.

As an example of a preferred embodiment of the present invention, a reactor is charged with a catalyst comprising a tertiary amine, an oxide of silicon and titanium and optionally a solvent, and the resulting mixture is heated and stirred, Hydrogen peroxide water is added dropwise over 0.5 to 10 hours to carry out the reaction. After completion of dropping the hydrogen peroxide solution, if the reaction is completed by continuing stirring at the same temperature for 0 to 5 hours, the target tertiary amine N-oxide is produced in high yield. In the reaction, the reaction temperature is room temperature to 100.
C, preferably 50 to 90C.

After completion of the reaction, the treatment of the reaction solution can be carried out by a combination of operations such as filtration, extraction, distillation and crystallization which are generally performed. For example, after completion of the reaction, the reaction solution is cooled to room temperature and potassium hydrogen sulfite is added to decompose unreacted hydrogen peroxide. Then, the treated solution is filtered to remove the catalyst, and the filtrate is concentrated to separate the precipitated crystals by filtration, or the filtrate is distilled to obtain a highly pure tertiary amine N-
The oxide can be obtained. The separated catalyst can be repeatedly used in the method of the present invention.

[0024]

EXAMPLES Next, the present invention will be further described with reference to examples, but the present invention is not limited to the following examples. The analysis conditions by liquid chromatography in the following examples are as follows.

Column: Intersil OS5 (Gaskuro Industrial Co., Ltd.) 4.6 mm φ × 250 mm Eluent: water / methanol (95/5 volume ratio) (however, water is KH ₂ PO ₄ 6.8 g, C in 1 liter)
₍ Containing 1.08 g of ₈ H ₁₇ SO ₃ Na and 1 ml of 85% H ₃ PO ₄ ) Flow rate: 0.5 ml / min Detection: UV 265 nm

Example 1 Titanosilicate TS-manufactured by NE Chem Cat Ltd. as a catalyst consisting of 30.0 g (0.379 mol) of pyridine and an oxide of silicon and titanium in a four-necked flask. 1 (Si / Ti atomic ratio = 16) (1.0 g) and water (30 g) were charged, and the mixture was stirred for 3 hours at 80 ° C. over 1.7 hours.
44.4 g (0.457 mol) of 5% hydrogen peroxide solution was added dropwise. Then, the mixture was kept at the same temperature for 2 hours with stirring. After completion of the reaction, the reaction solution was cooled, and a small amount of potassium hydrogen sulfite was added to the reaction solution to decompose unreacted hydrogen peroxide. After filtering this treatment liquid and separating the titanosilicate TS-1 by filtration, the filtrate was analyzed by liquid chromatography to find that pyridine N-oxide was quantitatively obtained from pyridine, that is, 36.1 g (0.379 mol). Was being generated.

Example 2 A four-necked flask was charged with 30.1 g (0.376 mol) of pyrazine, 1.0 g of the same titanosilicate as in Example 1 and 10.1 g of water, and 1.25 at 80 ° C. under stirring. 18.5 g (0.190 mol) of 35% hydrogen peroxide solution over time
Was dripped. Then, the mixture was kept at the same temperature for 2 hours with stirring.
After completion of the reaction, the reaction solution was cooled, and the reaction solution was filtered to separate the titanosilicate TS-1 by filtration. When the filtrate was analyzed by liquid chromatography, 17.5 g (0.182 mol) of pyrazine N-oxide was obtained, and the yield was 95.8% based on hydrogen peroxide. In addition, 0.25 g (0.0022 mol) of pyrazine N, N'-dioxide was formed.

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Claims (8)

[Claims] 1. A process for producing a tertiary amine N-oxide, which comprises reacting a tertiary amine with a peroxide in the presence of a catalyst composed of oxides of silicon and titanium. 2. The method according to claim 1, wherein the catalyst composed of an oxide of silicon and titanium is a catalyst containing silicon oxide and titanium oxide as a chemical composition or a compound. 3. The method according to claim 1, wherein the catalyst composed of oxides of silicon and titanium is a mixture of silicon oxide and titanium oxide, amorphous titanosilicate or crystalline titanosilicate. 4. The atomic ratio of silicon to titanium is Si / Ti = 1.
The method according to claim 1, 2 or 3, which is 0 to 200. 5. A catalyst comprising an oxide of silicon and titanium, wherein the atomic ratio of silicon to titanium is Si / Ti = 10 to 200.
2. The method according to claim 1, which is a crystalline titanosilicate. 6. The method according to claim 1, wherein the peroxide is hydrogen peroxide.
5. The method according to any one of 5 above. 7. The tertiary amine is a nitrogen-containing heteroaromatic compound, and the tertiary amine N-oxide is a nitrogen-containing heteroaromatic compound N-oxide.
The method described in the section. 8. The tertiary amine is pyridine or pyrazine, and the tertiary amine N-oxide is pyridine N-oxide or pyrazine N-oxide.
6. The method according to any one of 6 above.