JPH08301856A - Production of nitrogen-containing heterocyclic derivative - Google Patents

Abstract

PURPOSE: To safely produce a nitrogen-containing heterocyclic compound at a low cost by using a halogenated hydrocarbon or ether as a solvent, adding a nitrile and anhydrous aluminum chloride, introducing hydrogen chloride gas and reacting within a specific temperature range. CONSTITUTION: The objective nitrogen-containing heterocyclic derivative of formula III is produced by the co-trimerization reaction of (A) a halogenoacetonitrile of formula I (X is F, Cl or Br; (m) is an integer of 0-3) with (B) a nitrile of formula R-CN [R is an alkyl, an alkenyl, an aryl of formula II (R1 and R2 are each a halogen, amide, an alkylamine, etc.), etc.] in the presence of hydrogen chloride gas using anhydrous aluminum chloride as a catalyst. The co-trimerization reaction is carried out preferably by using a halogenated hydrocarbon or ether as the reaction solvent, adjusting the introducing amount of the gas to 1.0-3.0 times mol, the amount of the solvent to 1-10 times vol./wt. and the amount of the catalyst to 0.01-1.0 times mol based on the component B and keeping the reaction temperature between 0 deg.C and the boiling point of the solvent.

Description

Detailed Description of the Invention

[0001]

The present invention relates to a nitrogen-containing heterocyclic derivative,
It relates to an improved manufacturing method.

[0002]

2. Description of the Related Art A bis-4,6-trihalogenomethyl-s-triazine derivative substituted at the 2-position with an alkyl group, an aryl group or the like has excellent properties as a photopolymerization initiator. Various derivatives have been synthesized. Also, many patents have been filed regarding various photosensitive compositions (mixtures) containing these. As a method for producing the triazine, "Bulltein of the Chemical Society of Japan (Bulltein of the Chemical Society of Japan
Society of Japan) "Volume 42, page 2924, (19
1969), it is already well known that the co-trimerization reaction between two kinds of nitriles is the simplest method, and it contains bis-4,6-trihalogenomethyl-s-triazine. There are indeed numerous applications in composition-related patents.

The known reaction method described in Britain of the Chemical Society of Japan is
Free as a co-trimerization catalyst in the presence of gaseous hydrogen chloride.
Del Crafts catalysts such as AlCl ₃ , AlBr ₃ , Ti
It is possible to proceed by using Cl ₄ , BF ₃ · OC ₂ H _5, etc. However, as shown in the examples, since the activity of anhydrous aluminum bromide is the best and the reaction time and the reaction yield are superior to those of other Friedel-Crafts catalysts, the 2-position-substituted-bis- The production examples reported or cited in the composition-related patents of 4,6-halogenomethyl-s-triazine are mostly cases in which AlBr ₃ is used. Further, in these production examples, all of them carry out the reaction in a solventless system according to the above-mentioned known method.

This co-trimerization reaction is carried out by mixing two kinds of nitriles with a Friedel-Crafts type catalyst such as anhydrous aluminum bromide and then blowing hydrogen chloride gas into the mixture. Although the reaction system generally changes to a solution state at the initial stage of blowing hydrogen chloride gas,
In the latter half of blowing or at the end of blowing, crystals are precipitated to change into a thick paste state, and finally a solidified state where stirring is impossible. Since the reaction system undergoes such a state change, it is necessary in the conventional method to proceed the reaction in a non-stirred state, that is, in a state of standing.

[0005]

These points, which are characterized in the known methods, pose major problems from an industrial point of view. The first point is that although anhydrous aluminum bromide is preferred because of the high activity of the catalyst and the good yield it gives, the current situation is that this catalyst is small in production quantity and very expensive both in Japan and overseas. However, there are major problems in terms of difficulty in availability and cost. On the other hand, anhydrous aluminum chloride is a production method that replaces anhydrous aluminum bromide, even though it is produced in a large amount, is inexpensive, and is available in various forms from solid to fine powder. Things have not been advocated yet.

The second point is that hydrogen chloride is blown in the solventless reaction system, so that the reaction is necessarily forced to proceed in a solidified state. The solidification phenomenon occurs especially at the initial stage of the reaction until the blowing of hydrogen chloride is completed.Therefore, there is a problem of ensuring the safety of the equipment, a problem of quality / yield fluctuation due to partial reaction, and the mixture solidification in the reaction equipment. Therefore, there is a problem in that the removal processing is complicated and requires extra labor. It is not a preferable manufacturing method in terms of safety and stability of quality and yield. A good way to overcome this problem is to use a solvent to proceed the reaction under stirring, but all the production techniques up to now are only solventless methods, and the solvent usage method is Not advocated.

Since the triazine is one of the compounds useful as a photopolymerization initiator, there is a demand for an industrial production method which solves the above-mentioned problems and which can be carried out more inexpensively and more safely. The present invention overcomes the problems of these conventional techniques, and when co-trimerizing on an industrial scale,
It is an object of the present invention to provide a method for producing a nitrogen-containing heterocyclic derivative, which can use inexpensive aluminum chloride as a catalyst and can also carry out the reaction in the presence of a solvent.

[0008]

The above-mentioned problems in the prior art have been solved on an industrial scale by using anhydrous aluminum chloride as an alternative catalyst for anhydrous aluminum bromide and finding a suitable solvent which does not hinder the progress of the reaction. But it can be solved. In order to solve the drawbacks of the conventional method, the present inventors have conducted extensive studies as to a method for industrially producing the triazine, and as a result, methylene chloride,
After using halogenated hydrocarbons such as chloroform and carbon tetrachloride or ethers such as ethyl ether, tert-butyl methyl ether and 1,4-dioxane as a solvent and adding nitriles and anhydrous aluminum chloride thereto It was found that a nitrogen-containing heterocyclic derivative can be produced by injecting hydrogen chloride gas and performing the reaction under stirring at a temperature in the range of 0 ° C. or higher and the boiling point of the solvent or lower, and completed the present invention. It was

That is, the present invention has the general formula [I]

[Chemical 6] (In the formula, X represents fluorine, chlorine or bromine, and m is 0 to
Represents an integer of 3. ) Halogenoacetonitrile represented by the general formula [II]

[Chemical 7] [In the formula, R is an optionally substituted alkyl group, an optionally substituted alkenyl group, an alkylaryl group, an optionally substituted heterocyclic residue, and the following formula [III]

Embedded image (In the formula, R1 and R2 represent a halogen atom, an amide group, an alkylamino group, an alkylthio group, an alkoxy group, an alkyl group, an alkenyl group or an aryl group, and each may be the same or different, Further, R1 and R2 may be linked to each other to form an alkylene group or a condensed aromatic ring.). ] The nitrile represented by the following general formula [IV], characterized by using anhydrous aluminum chloride as a catalyst in the presence of hydrogen chloride gas to co-trimerize

[Chemical 9] [In the formula, X represents fluorine, chlorine or bromine, m represents an integer of 0 to 3, R represents an optionally substituted alkyl group, an optionally substituted alkenyl group, an alkylaryl group, Heterocyclic residue which may be substituted, represented by the following formula [V]

[Chemical 10] (In the formula, R1 and R2 represent a halogen atom, an amide group, an alkylamino group, an alkylthio group, an alkoxy group, an alkyl group, an alkenyl group or an aryl group, and each may be the same or different, Further, R1 and R2 may be linked to each other to form an alkylene group or a condensed aromatic ring.). ] It is a manufacturing method of the nitrogen-containing heterocyclic derivative represented by these. Further, it is a method for producing a nitrogen-containing heterocyclic derivative in which a halogenated hydrocarbon or an ether is used as a reaction solvent when performing a co-trimerization reaction.

According to the present invention, aluminum chloride selected as a catalyst in this co-trimerization reaction can be used in the form of a lump or a powder as long as it is an anhydrous product. As such anhydrous aluminum chloride, commercially available blocks, powders and the like can be used as they are. When it is desired to smoothly start the reaction, the dissolution rate control of aluminum chloride is effective, so that it is preferable to select a powdery one rather than a blocky one. The amount of anhydrous aluminum chloride used can be in the range of 0.01 to 1.0 times the molar ratio of the nitrile represented by [II]. This amount may be selected based on the relationship between the reaction progress rate and the slurry concentration,
Generally, it is 0.1 with respect to the nitrile represented by [II].
A preferable molar ratio is 0.3 to 0.3 times. It goes without saying that anhydrous aluminum bromide, which has been widely used in the conventional production technique of the s-triazine derivative, can be applied to the production method of the present invention in the same molar range as the above-mentioned anhydrous aluminum chloride.

When the co-trimerization is promoted, the production method of the present invention is characterized by using a solvent, which is superior to the conventional method. That is, the problem that was essentially impossible in the conventional method by using a solvent,
That is, it is possible to continuously and continuously agitate the reaction from the step of injecting hydrogen chloride gas to the step of ending the reaction, and to proceed the reaction uniformly and efficiently. The temperature of the reaction system can be easily controlled, and the local reaction that accompanies solidification is avoided, resulting in excellent reproducibility of the reaction. Furthermore, since there is no solidification of the reaction product, the post-treatment is very smooth and simple. There is.
In the conventional method, when treating the solidified reaction mixture, it is indispensable to loosen the mixture in the solidified state, such as adding a suitable solvent and heating and melting the mixture once. Although it takes time, these complicated treatments are unnecessary in the production method of the present invention which is carried out in a solvent system. At the end of the reaction, it is possible to immediately carry out a catalyst removal treatment by washing with water, and then smoothly proceed a series of steps of liquid separation, concentration, and crystallization. As the solvent used here, halogenated hydrocarbons and ethers can be applied. The kind of these solvents is not particularly limited as long as it is a solvent in a commonly used range, but regarding halogenated hydrocarbons, for example, methylene chloride, chloroform, carbon tetrachloride, 1,2
Aliphatic halogenated hydrocarbons such as dichloroethane can be used.

On the other hand, regarding ethers, for example, 1,4
-Dioxane, diethyl ether, tert-butyl methyl ether, diisopropyl ether and the like can be used.

On the other hand, aliphatic hydrocarbons and aromatic hydrocarbons whose polarities are lower than those of halogenated hydrocarbons and ethers are difficult to apply to the production method of the present invention.
This is because in the latter aromatic hydrocarbon solvent, a Friedel-Crafts type reaction mediated by aluminum chloride progresses with trichloroacetonitrile, so that the reaction product becomes complicated and, in general, these This is because the activity of the catalyst is reduced in a low-polarity solvent, and the formation of triazine is extremely reduced or the reaction does not proceed at all. In the above-mentioned halogenated hydrocarbon or ether type solvent system, such side reaction hardly occurs and the reaction proceeds cleanly.

The reaction is started by blowing hydrogen chloride gas into a mixture of two nitriles (eg trichloroacetonitrile and p-anisonitrile), anhydrous aluminum chloride and a solvent. The molar ratio of hydrogen chloride to be blown is appropriately 1.0 to 3.0 times that of the nitrile shown in [II]. Although the reaction proceeds even if the amount is more than this amount, the production amount of the target triazine gradually decreases, and unnecessary amount dissipates out of the system. preferable.

Regarding the method of introducing hydrogen chloride, it is possible to charge the nitriles, the solvent, and the catalyst in this manner, and then to blow the reaction mixture. When blowing, the reaction mixture is cooled in advance in order to help the absorption of hydrogen chloride. It is desirable to keep it. On the other hand, it is also possible to absorb hydrogen chloride in a solvent in advance to carry out the reaction. For example, 1,
Even if a 4-dioxane solvent in which a necessary amount of hydrogen chloride is absorbed is used, there is no adverse effect on the reaction. However, with regard to halogenated hydrocarbon solvents, most of them reach the solution saturation before absorbing the required amount of hydrogen chloride, and hydrogen chloride becomes insufficient. Therefore, a method in which hydrogen chloride gas is blown after absorbing all reagents Is more suitable.
As described above, with respect to the blowing of hydrogen chloride, either a method of preliminarily absorbing the solvent in the solvent or a method of preliminarily absorbing all the reagents and then absorbing can be applied depending on the hydrogen chloride-dissolving ability of the solvent used. If either method can be used, it does not matter which method is used.

Regarding the reaction temperature, it is preferable that the step of blowing hydrogen chloride gas is carried out by cooling to 0 to 12 ° C.
After the required amount of hydrogen chloride has been introduced, the reaction can be carried out in the range of room temperature to the boiling point of the solvent used. The reaction rate is accelerated by increasing the temperature, but at high temperature, hydrogen chloride also dissipates, so 20 ° C to 35 ° C.
It is preferable to carry out.

By carrying out the reaction under the above-mentioned conditions,
The co-trimerization reaction between nitriles represented by [I] and [II] proceeds smoothly, and the nitrogen-containing heterocyclic derivative represented by [IV] can be obtained in good yield. When the reaction is carried out by this method, the amount of aluminum chloride is used in a 0.01 to 1.0-fold molar ratio with respect to the nitrile represented by [II] as described above. The obtained nitrogen-containing heterocyclic derivative may have a slight yellowish color. This phenomenon is not characteristic of the method of the present invention, nor is it limited to aluminum chloride.
This is because it is confirmed that even in the conventional method of using anhydrous aluminum bromide in a solvent-free system, similar coloring is observed when the amount used is increased. However, since the use of s-triazine is for photopolymerization initiators in particular, it is required that the s-triazine is not only highly pure but also has good color without coloring due to impurities. Therefore, it is necessary to avoid such coloring.
As a result of intensive studies on this decolorization method, the present inventors have found that the magnesium silicate-based adsorption treatment agent exerts an effect on decolorization. That is, after the reaction solution was washed with water, a magnesium silicate-based adsorption treatment agent was added, the mixture was kept stirring at room temperature for 1 hour, and then the adsorption agent was separated by filtration to obtain the s- It was confirmed that triazine can be obtained.

The magnesium silicate may be commercially available, for example, "Kyoward" adsorbent manufactured by Kyowa Kagaku or "Florisil" manufactured by Wako Pure Chemical Industries.
Can be used. The amount used is not particularly limited, but is 0.05 times weight to 3.0 times the weight of triazine.
A decolorizing effect is recognized in the double weight range. As the solvent for decolorization, the solvent used in the reaction, that is, the halogenated hydrocarbon or ether solvent can be used as it is. Further, aliphatic hydrocarbons (eg, n-hexane, cyclohexane, etc.) and aromatic hydrocarbons (eg, toluene, xylene, etc.) that can be used in ordinary synthesis can also be used. In the case of a highly water-soluble solvent such as 1,4-dioxane, washing with water becomes difficult, so it is necessary to replace the solvent with a hydrocarbon-based solvent before decolorization. From the viewpoint of properties, it is preferable to perform the decolorization treatment in the halogenated hydrocarbon or ether solvent used as the reaction solvent.

The present invention will be described in detail with reference to the following examples, but the present invention is not limited thereto.

[0020]

Example 1 In a nitrogen atmosphere, 2,222.2 g of trichloroacetonitrile, 1,219.29 g of p-anisonitrile, 244.2 g of anhydrous aluminum chloride and 3,200 of 1,2-dichloroethane.
After cooling the mixture consisting of mL to an internal temperature of 0 ° C., while stirring, 367.66 g of dry hydrogen chloride gas was introduced over 0.5 hour. In the latter stage of introduction, the system changed to a slurry state. The internal temperature was raised to 35 ° C., and the reaction was carried out at the same temperature under stirring for 40 hours. After 5,000 g of water was added to dissolve the catalyst and the inorganic salt, 2,400 g of Kyoward as a decolorizing agent was added to the separated 1,2-dichloroethane layer simultaneously with anhydrous magnesium sulfate, and the mixture was treated for 1 hour.
The desiccant and decolorizer were separated by filtration. 1,2 obtained
After concentrating the dichloroethane solution, the crude product obtained is recrystallized from isopropyl alcohol to give 2- (p-methoxyphenyl) -bis-4,6-trichloromethyl-s-triazine as white needles. 2,272.8g was acquired.
Yield 70%. Purity 99.7%.

[0021]

Example 2 Under a nitrogen atmosphere, 2,222.2 g of trichloroacetonitrile and 1,457.7 of p-methoxycinnamate nitrile were used.
g, 244.2 g of anhydrous aluminum chloride, and 2,400 mL of 1,4-dioxane were kept at an internal temperature of 12 ° C., and then 367.66 g of dry hydrogen chloride gas was introduced over 0.5 hours with stirring. Raise the internal temperature to 35 ° C, and at the same temperature, 4
The reaction was carried out for 0 hours. After the reaction, 1,4-dioxane was concentrated, 15,000 mL of toluene was added, and then an inorganic salt was dissolved and separated with 5,000 g of water. After adding 3000 g of Kyoward together with anhydrous magnesium sulfate to the liquid-separated toluene layer and stirring the mixture at room temperature for 1.5 hours, the desired product, 2- (p-methoxystyryl), was obtained in the same manner as in Example 1. -Bis-
4,6-Trichloromethyl-s-triazine 2,240.6g
Got Yield 65%. Purity 99.5%.

[0022]

Comparative Example 1 Under a nitrogen atmosphere, a mixture of 2,222.2 g of trichloroacetonitrile, 1,219.3 g of p-anisonitrile and 488.4 g of anhydrous aluminum bromide was cooled to an internal temperature of 0 ° C., and then dried under stirring with dry hydrogen chloride 367.7. g was introduced over 0.5 hour. In the latter half of the introduction, the whole was in a solidified state and stirring was impossible. It was left standing as it was and heated to 35 ° C. to continue the reaction. The reaction composition reached the ceiling in about 40 hours. After adding 13,000 mL of 1,2-dichloroethane to the resulting solid and heating and refluxing to melt the solid, 5,000 g of water was added to wash the solid, and the separated 1,2-dichloroethane layer was dried over anhydrous magnesium sulfate. Was added. After the drying agent was separated by filtration, the obtained toluene layer was concentrated and recrystallized twice from isopropyl alcohol to give slightly yellow 2- (p-methoxyphenyl) -bis-4,6-trichloromethyl-s. − Triazine 1,948.1
g was obtained. Yield 60%. Purity 99.1%

[0023]

INDUSTRIAL APPLICABILITY In the present invention, when a nitrogen-containing heterocyclic derivative derivative is produced by a co-trimerization reaction of an alkyl- or aryl-substituted nitrile and haloacetonitrile,
In the past, expensive aluminum bromide was exclusively used, but it became possible to use inexpensive aluminum chloride catalysts, and the use of solvents such as alkyl halides and ethers resulted in the solidification phenomenon which was a problem in the prior art. Can be avoided altogether. Further, in the production method according to the present invention, since the decolorization treatment with the magnesium silicate-based adsorbent is adopted, it is possible to obtain triazine having a good color with almost no coloring due to impurities. Triazine is a high-purity product having almost the same purity and quality as those obtained by conventional methods, and can be sufficiently used as a photopolymerization initiator. By this method, various nitrogen-containing heterocyclic derivatives can be industrially produced.

Claims (4)

[Claims] 1. A compound represented by the general formula [I]: (In the formula, X represents fluorine, chlorine or bromine, and m is 0 to
Represents an integer of 3. ) And a halogenoacetonitrile represented by the general formula [II] [Wherein R is an optionally substituted alkyl group, an optionally substituted alkenyl group, an alkylaryl group, an optionally substituted heterocyclic residue, or a compound represented by the following formula [III]: (In the formula, R1 and R2 represent a halogen atom, an amide group, an alkylamino group, an alkylthio group, an alkoxy group, an alkyl group, an alkenyl group or an aryl group, and each may be the same or different, Further, R1 and R2 may be linked to each other to form an alkylene group or a condensed aromatic ring.). ] The nitrile represented by the general formula [IV] is characterized in that it is trimerized with anhydrous aluminum chloride in the presence of hydrogen chloride gas as a catalyst. [In the formula, X represents fluorine, chlorine or bromine, m represents an integer of 0 to 3, R represents an optionally substituted alkyl group, an optionally substituted alkenyl group, an alkylaryl group, An optionally substituted heterocyclic residue, of the following formula [V] (In the formula, R1 and R2 represent a halogen atom, an amide group, an alkylamino group, an alkylthio group, an alkoxy group, an alkyl group, an alkenyl group or an aryl group, and each may be the same or different, Further, R1 and R2 may be linked to each other to form an alkylene group or a condensed aromatic ring.). ] The manufacturing method of the nitrogen-containing heterocyclic derivative represented by these. 2. The method for producing a nitrogen-containing heterocyclic derivative according to claim 1, wherein a halogenated hydrocarbon or an ether is used as a reaction solvent when carrying out the co-trimerization reaction. 3. When the co-trimerization reaction is carried out, the general formula [I
I], the amount of hydrogen chloride gas blown is 1.0 to 3.0 times the molar ratio, the solvent used is 1 to 10 times the volume / weight ratio, and anhydrous aluminum chloride is used. The method for producing a nitrogen-containing heterocyclic derivative according to claim 2, wherein the amount is 0.01 to 1.0 times the molar ratio, and the reaction temperature is 0 ° C or higher and the boiling point of the solvent to be used or lower. 4. A method for producing a nitrogen-containing heterocyclic derivative according to claim 1, wherein the co-trimerization reaction mixture is washed with water and then decolorized by adding a magnesium silicate adsorbent. Method.