JP5167283B2 - Process for producing phenyltriazolinones - Google Patents

Description

  The present invention relates to a method for producing phenyl-1,2,4-triazolin-5-ones, and more specifically, phenyl-1,2,4 which is a compound useful as a raw material or intermediate for the synthesis of pharmaceuticals and agricultural chemicals. -It relates to a process for producing triazolin-5-ones.

  Phenyl-1,2,4-triazolin-5-ones (phenyltriazolinones) are useful compounds as raw materials or intermediates for pharmaceuticals and agricultural chemicals, and various production methods have been proposed heretofore. .

  For example, PCT International Publication No. WO 98/38176 (Patent Document 1) describes that phenyltriazolinones are produced by the following reaction.

（式中、ｎは０または１〜５の整数であり、Ｘは同一でも異なっていてもよく、ハロゲン原子、低級アルキル基、低級ハロアルキル基などを示す。）
しかしながら該特許文献１に記載の方法では、反応工程でフェニルヒドラゾン（Ａ−３）を単離しなければならず、また、製造時に高価なアジ化ジフェニルホスホリル（Ａ−４）を用いており、フェニルトリアゾリノン（Ａ−５）を製造する上でコスト高となる。

(In the formula, n is 0 or an integer of 1 to 5, and X may be the same or different and represents a halogen atom, a lower alkyl group, a lower haloalkyl group, etc.)
However, in the method described in Patent Document 1, phenylhydrazone (A-3) must be isolated in the reaction step, and expensive diphenylphosphoryl azide (A-4) is used during production. The production cost of triazolinone (A-5) increases.

Therefore, it is difficult to say that the above-described production method described in Patent Document 1 is an industrially advantageous production method.
PCT International Publication No. WO02 / 12203 (Patent Document 2)
General formula (B-1):

（式（Ｂ−１）中、Ｘは、ハロゲン原子、炭素数１〜６の低級アルキル基を示し、ｎは０〜５の整数を示す。ｎが２以上の整数を示す場合、複数個のＸは互いに同一でも異なっていてもよい。）に示すアリールトリアゾリノン類を製造するに際して、アリールヒドラゾン（Ｂ−３）を、シアン酸アルカリ金属塩および酸と反応させて、アリールトリアゾリジノン（Ｂ−２）を形成し、次いで、酸化剤と反応させる工程を有するアリールトリアゾリノン類の製造法が開示されている。

(In formula (B-1), X represents a halogen atom or a lower alkyl group having 1 to 6 carbon atoms, n represents an integer of 0 to 5. When n represents an integer of 2 or more, a plurality of X may be the same as or different from each other.), The aryl hydrazone (B-3) is reacted with an alkali metal cyanate and an acid to produce an aryl triazolidinone ( A process for producing aryltriazolinones having the step of forming B-2) and then reacting with an oxidizing agent is disclosed.

  However, the formaldehyde-aryl hydrazone represented by the general formula (B-3) can be converted into a tetrazine derivative by coupling the hydrazone with an acid, as described in “Liebigs Ann. Chem., 635 (1960), 82”. -91pp "(Non-Patent Document 1).

That is, the formaldehyde-aryl hydrazone represented by the general formula (B-3) is unstable in the presence of an acid.
Therefore, in the method of reacting aryl hydrazone (B-3) and alkali metal cyanate in the presence of acid according to Patent Document 2, side reactions increase, which may adversely affect the yield and purity of the target product. Therefore, it is not necessarily a preferable method.

Note that Japanese Patent Publication No. 6-78322 (Patent Document 3) corresponding to PCT International Publication No. WO91 / 3470
General formula (C-1):

（式（Ｃ−１）中、ｎは１〜３の整数であり、Ｒはハロゲン原子、アルキル基、ハロアルキル基などを示し、Ｘは、各々独立に水素、ハロゲン原子（Ｃｌ、Ｂｒ、Ｉ）、低級アルキル基などを示す。）で示されるアリールトリアゾリジノンを、次亜ハロゲン酸または次亜ハロゲン酸塩で処理する、
一般式（Ｃ）：

(In formula (C-1), n is an integer of 1 to 3, R represents a halogen atom, an alkyl group, a haloalkyl group, or the like, and X is independently a hydrogen atom or a halogen atom (Cl, Br, I). , An aryl triazolidinone represented by a lower alkyl group, etc.) is treated with hypohalous acid or hypohalite.
Formula (C):

（式（Ｃ）中、ｎは１〜３の整数であり、Ｒはハロゲン原子、アルキル基、ハロアルキル基などを示し、Ｘは、各々独立に水素、ハロゲン原子、低級アルキル基などを示す。）に示すアリールトリアゾリノンの製造方法が記載されている。

(In the formula (C), n is an integer of 1 to 3, R represents a halogen atom, an alkyl group, a haloalkyl group, etc., and X independently represents a hydrogen atom, a halogen atom, a lower alkyl group, etc.) A method for producing an aryltriazolinone shown in FIG.

In addition, in Japanese Translation of PCT International Publication No. 7-503253 (Patent Document 4) corresponding to PCT International Publication WO 93/23382,
Formula (D):

（式（Ｄ）中、Ｒは低級アルキル基であり、Ｘは独立してハロゲン、低級アルキル、ニトロ、ヒドロキシ、ＮＨＳＯ₂Ｒ'、−Ｎ（ＳＯ₂Ｒ'）₂、−Ｎ（Ｒ'）ＳＯ₂Ｒ'（但し、Ｒ'は低級アルキル）であり、ｎは０〜３の整数である。）のアリールトリアゾリノンを製造する方法において、第三級ブタノール溶媒中で、式：Ｘ_n−Ｐｈ−ＮＨ・ＮＨ₂（Ｐｈ：フェニル、Ｘ、ｎは特許文献３と同様）で示されるアリールヒドラジンを、(i)Ｃ１〜Ｃ３アルデヒド、(ii)シアナート及び弱有機酸、及び(iii)次亜塩素酸、その塩又はハロゲンにより順次処理するアリールトリアゾリノンの製造法が開示されている。

(In the formula (D), R is a lower alkyl group, X is independently halogen, lower alkyl, nitro, hydroxy, NHSO ₂ R ′, —N (SO ₂ R ′) ₂ , —N (R ′)). In a process for producing an aryltriazolinone of SO ₂ R ′ (where R ′ is a lower alkyl) and n is an integer from 0 to 3), in a tertiary butanol solvent, the formula: X _n An aryl hydrazine represented by -Ph-NH.NH ₂ (Ph: phenyl, X, n is the same as in Patent Document 3), (i) C1-C3 aldehyde, (ii) cyanate and weak organic acid, and (iii) A process for the production of aryltriazolinones by sequential treatment with hypochlorous acid, its salts or halogens is disclosed.

  However, Patent Documents 3 and 4 do not describe or suggest any phenyltriazolinones in which R is hydrogen (H) in the formula (C) or (D) and the production method thereof. Absent.

WO98 / 38176 WO02 / 12203 Japanese Patent Publication No. 6-78322 JP 7-503253 A

Liebigs Ann. Chem., 635 (1960), 82-91pp

  The present invention seeks to solve the problems associated with the prior art as described above, and uses simpler, safer, lower cost and higher purity phenyl triazolinones by using cheaper raw materials. It aims at providing the novel manufacturing method of phenyl triazolinone which can be manufactured with a yield.

  As a result of intensive studies to achieve the above object, the present inventors formed formaldehyde-phenylhydrazones (also referred to as phenylhydrazones) under a specific pH range, and further obtained formaldehyde- It was found that phenyltriazolinones can be produced in high yield and high purity without causing the above side reaction by reacting phenylhydrazones with cyanic acid to form phenyltriazolidinones.

That is, the present inventors
(1) Formaldehyde-phenylhydrazone of coexisting acid by handling formaldehyde-phenylhydrazone in a specific pH range in the reaction step of forming phenyltriazolidinones from aniline via formaldehyde-phenylhydrazone Alleviate and reduce the adverse effects on the product (byproduct of tetrazine derivatives)
(2) Further, it was found that phenyl triazolinones, which are target substances, can be produced in high yield and high purity by cycloaddition of cyanic acid to formaldehyde-phenylhydrazones.

  In addition, the present inventors have found that inexpensive and versatile anilines can be selected as raw materials in the production of phenyltriazolinones, and if necessary, the risk of fire, explosion, etc. and the harmfulness to health It is possible to avoid storing chemical substances such as phenylhydrazine, which are of concern.

  Furthermore, the present inventors have also found that all steps can be performed by continuous processing. This makes it possible to produce the target phenyltriazolinones more safely without going through dangerous purification steps, and to make the method suitable for large-scale industrial implementation. It was possible.

As described above in detail, the present inventors can produce high-purity phenyltriazolinones (5) in a high yield at a low cost, safely and efficiently, and complete the present invention. It came.
Examples of the method for producing phenyltriazolinones according to the present invention include the following first production method, second production method, third production method, fourth production method, and fifth production method. Is preferred.

The first production method according to the present invention includes:
General formula (1)

（式（１）中、Ｘは、ハロゲン原子、炭素数１〜６の低級アルキル基を示し、ｎは、０〜５の整数を示す。ｎが２以上の整数を示す場合、複数個のＸは互いに同一でも異なっていてもよい。）に示すアニリン類を亜硝酸塩類と反応させてジアゾニウム塩とした後、亜硫酸塩類又は亜硫酸水素塩類を用いて還元し、次いで、加水分解することにより
一般式（２）

(In formula (1), X represents a halogen atom or a lower alkyl group having 1 to 6 carbon atoms, n represents an integer of 0 to 5. When n represents an integer of 2 or more, a plurality of X May be the same as or different from each other.) An aniline shown in the above is reacted with nitrite to form a diazonium salt, then reduced using sulfite or bisulfite, and then hydrolyzed to form the general formula. (2)

（式（２）中、Ｘ、ｎは、式（１）中のものと同じ。）
に示すフェニルヒドラジン類を形成し、次いで、
得られたフェニルヒドラジン類（２）とホルムアルデヒドとを触媒存在下、ｐＨ５〜１０において反応させて、
一般式（３）

(In formula (2), X and n are the same as those in formula (1).)
The phenylhydrazines shown below,
The obtained phenylhydrazine (2) and formaldehyde are reacted at pH 5-10 in the presence of a catalyst,
General formula (3)

（式（３）中、Ｘ、ｎは、式（１）中のものと同じ。）
に示すホルムアルデヒド−フェニルヒドラゾン類を形成し、次いで、
このホルムアルデヒド−フェニルヒドラゾン類（３）とシアン酸とを反応させて、
一般式（４）

(In formula (3), X and n are the same as those in formula (1).)
Formaldehyde-phenylhydrazones as shown in FIG.
The formaldehyde-phenylhydrazone (3) is reacted with cyanic acid,
General formula (4)

（式（４）中、Ｘ、ｎは、式（１）中のものと同じ。）
に示すフェニルトリアゾリジノン類を形成し、次いで、
このフェニルトリアゾリジノン類（４）と、
次亜ハロゲン酸塩および酸素のうちから選択される酸化剤とを、無触媒下または酸化触媒存在下に反応させることを特徴とする
一般式（５）

(In formula (4), X and n are the same as those in formula (1).)
The phenyl triazolidinones shown in
These phenyl triazolidinones (4),
A general formula (5), characterized by reacting a hypohalite and an oxidant selected from oxygen in the absence of a catalyst or in the presence of an oxidation catalyst

（式（５）中、Ｘ、ｎは、式（１）中のものと同じ。）
に示すフェニルトリアゾリノン類の製造法
である。

(In formula (5), X and n are the same as those in formula (1).)
It is a manufacturing method of phenyl triazolinones shown in the following.

In the second production method according to the present invention,
General formula (2)

（式（２）中、Ｘ、ｎは、式（１）中のものと同じ。）
に示すフェニルヒドラジン類を含む反応混合物から、濾過、デカンテーションなどで必要に応じて水層を除去することによってフェニルヒドラジン類（２）の粗生成物を分離してもよい。

(In formula (2), X and n are the same as those in formula (1).)
The crude product of phenylhydrazines (2) may be separated from the reaction mixture containing phenylhydrazines by removing the aqueous layer as necessary by filtration, decantation or the like.

In the third production method according to the present invention,
General formula (3)

（式（３）中、Ｘ、ｎは、式（１）中のものと同じ。）
に示すホルムアルデヒド−フェニルヒドラゾン類を含む反応混合物から、濾過、デカンテーションなどで必要に応じて水層を除去することによってホルムアルデヒド−フェニルヒドラゾン類（３）の粗生成物を分離してもよい。

(In formula (3), X and n are the same as those in formula (1).)
The crude product of formaldehyde-phenylhydrazone (3) may be separated from the reaction mixture containing formaldehyde-phenylhydrazone shown in the above by removing the aqueous layer by filtration, decantation or the like, if necessary.

In the fourth production method according to the present invention,
General formula (1)

（式（１）中、Ｘは、ハロゲン原子、炭素数１〜６の低級アルキル基を示し、ｎは、０〜５の整数を示す。ｎが２以上の整数を示す場合、複数個のＸは互いに同一でも異なっていてもよい。）に示すアニリン類を必要に応じて有機溶媒の存在下に亜硝酸塩類と反応させてジアゾニウム塩としてもよい。

(In formula (1), X represents a halogen atom or a lower alkyl group having 1 to 6 carbon atoms, n represents an integer of 0 to 5. When n represents an integer of 2 or more, a plurality of X May be the same or different from each other.) The anilines shown in the above may be reacted with nitrites in the presence of an organic solvent to form a diazonium salt, if necessary.

In the fifth production method according to the present invention,
General formula (4)

（式（４）中、Ｘ、ｎは、式（１）中のものと同じ。）に示すフェニルトリアゾリジノン類と、次亜ハロゲン酸塩および酸素のうちから選択される酸化剤とを、無触媒下または酸化触媒存在下に反応させた後に、必要に応じてアルカリで処理することによって、
前記一般式（５）

(In formula (4), X and n are the same as those in formula (1)), and an oxidizing agent selected from hypohalite and oxygen, After reacting in the absence of a catalyst or in the presence of an oxidation catalyst, by treating with alkali as necessary,
General formula (5)

（式（５）中、Ｘ、ｎは、式（１）中のものと同じ。）
に示すフェニルトリアゾリノン類を精製してもよい。

(In formula (5), X and n are the same as those in formula (1).)
The phenyltriazolinones shown in (1) may be purified.

In the process for producing phenyltriazolinones (5) according to the present invention, the reaction is completed at a relatively low temperature in a short time, and high-purity phenyltriazolinones (5) can be obtained in a high yield.
In addition, the method for producing phenyltriazolinones (5) according to the present invention can be carried out continuously without isolating or purifying the intermediate produced in each step, so that it is efficient and safe with a small amount of energy. In addition, the phenyl triazolinones (5) can be provided at low cost. Therefore, the method for producing phenyltriazolinones of the present invention is also suitable for large-scale industrial implementation.

Hereinafter, the best mode for carrying out the process for producing phenyltriazolinones according to the present invention will be specifically described.
In the method for producing phenyltriazolinones according to the present invention, phenyltriazolinones represented by the following formula (5) are produced through a series of reaction steps represented by the following <formula A>.

In this production method, phenyltriazolinones represented by the following formula (5) are produced from the anilines (1) as a raw material through the following first to fourth steps.
That is, in this method for producing phenyl triazolinones (5), in the first stage, anilines (1) are reacted with nitrites to form diazonium salts, and then reduced using sulfites or bisulfites. And then hydrolyzing to form phenylhydrazines (2).

  This phenylhydrazines (2) is a crude product of the phenylhydrazines (2) obtained by removing the aqueous layer from the reaction mixture by filtration, decantation, etc. without isolation from the standpoint of improving yield purity. The product or aqueous suspension may be used for the next step.

  From the viewpoint of yield improvement and purity improvement, the anilines (1) are reacted with nitrites in the presence of an organic solvent to form a diazonium salt, and then reduced using sulfites or bisulfites, The phenylhydrazines (2) may be formed by hydrolysis.

  Next, in the second stage, the obtained phenylhydrazines (2) and formaldehyde are reacted in the presence of a catalyst, preferably under a specific pH (pH 5 to 10) to form formaldehyde-phenylhydrazones (3). To do.

  The formaldehyde-phenylhydrazones (3) are obtained by removing the aqueous layer from the reaction mixture by filtration, decantation, etc. without isolation from the viewpoint of improving yield purity, etc. The crude product or aqueous suspension of 3) may be used in the next step.

Next, in the third stage, the formaldehyde-phenylhydrazone (3) and cyanic acid are reacted to form phenyltriazolidinones (4).
The phenyltriazolidinones (4) are often subjected to the next step (fourth stage) without isolation and purification.

  Next, in the fourth stage, the phenyl triazolidinones (4) are reacted with an oxidizing agent selected from hypohalite and oxygen in the absence of a catalyst or in the presence of an oxidation catalyst, to give phenyl. Triazolinones (5) are produced.

The phenyltriazolinones (5) may be purified by treating with alkali after the completion of the reaction from the viewpoint of improving the purity.
In the method according to the present invention, the phenylhydrazines (2) may be isolated if necessary, and the formaldehyde-phenylhydrazones (3) (also referred to as phenylhydrazones) may be isolated if necessary. Also good.

In the production method according to the present invention, the water layer may be removed at any of the first stage and the second stage.
<Formula A>

一般式（１）〜（５）中、Ｘは、ハロゲン原子、炭素数１〜６の低級アルキル基を示し、ｎは０〜５の整数を示す。ｎが２以上の整数を示す場合、複数個のＸは互いに同一でも異なっていてもよい。

In general formulas (1) to (5), X represents a halogen atom or a lower alkyl group having 1 to 6 carbon atoms, and n represents an integer of 0 to 5. When n shows an integer greater than or equal to 2, several X may mutually be same or different.

The “halogen atom” includes chlorine, bromine, fluorine, and iodine atoms.
In the general formulas (1) to (5), when X is “lower alkyl”, examples of the lower alkyl group include alkyl groups having 1 to 6 carbon atoms, which may be linear or branched. For example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl, t-butyl, n-pentyl, isopentyl, 2-methylbutyl, neopentyl, n-hexyl, 4-methylpentyl, 2,3-dimethylbutyl, 1-ethylbutyl, 1-ethyl-2-methyl-propyl, 1-methyl-1-ethylpropyl, 1-methyl-2-ethylpropyl, 2-methyl-1-ethylpropyl, 2- Examples thereof include a methyl-1-ethylpropyl group and a 2-methyl-2-ethylpropyl group.
Furthermore, the phenylhydrazines (2) may or may not be a salt.

<Synthesis of phenylhydrazine (2) (first stage)>
First, in the “first stage”, the aniline represented by the general formula (1) is converted into a diazonium salt with nitrites, and the obtained diazonium salt is reduced with sulfites or hydrogen sulfites, It is preferable to obtain the corresponding phenylhydrazines represented by the general formula (2) by hydrolysis.

Specifically, for example, anilines (1) as a raw material are reacted with hydrochloric acid to form a salt.
Then, sodium nitrite is added to the hydrochloride to diazotize, and the diazotate is then added to a solution of sodium sulfite adjusted to a pH of 5.5 to 8.0, and further hydrolyzed to phenyl. Hydrazines (2) are produced.

  The starting aniline (1) is reacted with hydrochloric acid in the presence of an organic solvent to form a salt, then sodium nitrite is added to the hydrochloride to diazotize the diazotized product, and the pH of the diazotized product is 5.5. The phenylhydrazines (2) can also be produced by reducing and further hydrolyzing the sodium sulfite solution adjusted to ˜8.0.

  The diazotization, reduction, and hydrolysis in the first stage can be carried out according to known methods. For the purpose of explaining the reaction process in the first stage in more detail, preferred examples in the production method according to the present invention are as follows. Show.

  In the first stage diazotization, the aniline (1) is first reacted with, for example, hydrochloric acid to form a salt, or the aniline (1) is reacted with hydrochloric acid in the presence of an organic solvent to form a salt. In this case, hydrochloric acid is used excessively in this example.

次に、例えば亜硝酸ナトリウムを加えてジアゾ化する。

Next, for example, sodium nitrite is added to diazotize.

次いで、上記ジアゾ化物を、例えば硫酸でｐＨを調整した亜硫酸ナトリウムの溶液に加えて還元する。

Next, the diazotized product is reduced by adding it to a solution of sodium sulfite whose pH is adjusted with, for example, sulfuric acid.

次に、生じたフェニルヒドラジンスルホナート類を加水分解することでフェニルヒドラジン類の塩を得る。

Next, the resulting phenylhydrazine sulfonates are hydrolyzed to obtain a salt of phenylhydrazines.

なお、必要に応じて、得られたフェニルヒドラジン類の塩を中和してもよい。

In addition, you may neutralize the salt of the obtained phenylhydrazines as needed.

このようなジアゾニウム塩を生成させるジアゾ化反応は、通常、−２５℃〜２５℃までの温度範囲、好ましくは−５℃〜２０℃の温度で、１５分〜２時間、好ましくは３０分〜１時間、常圧下に行われる。ジアゾ化剤として用いられる亜硝酸塩類としては、具体的には、亜硝酸ナトリウム、亜硝酸カリウムなどが挙げられ、亜硝酸ナトリウムが好ましい。

The diazotization reaction for producing such a diazonium salt is usually at a temperature range of -25 ° C to 25 ° C, preferably at a temperature of -5 ° C to 20 ° C, for 15 minutes to 2 hours, preferably 30 minutes to 1 °. Performed under normal pressure for hours. Specific examples of the nitrites used as the diazotizing agent include sodium nitrite and potassium nitrite, and sodium nitrite is preferred.

  The amount of nitrite used is usually 1.0 to 1.5 mol, preferably 1.0 to 1.2 mol, based on 1 mol of anilines (1). However, it is usually used as an aqueous solution.

  Further, for such diazotization reaction, a mineral acid is usually used, and examples thereof include hydrochloric acid, sulfuric acid, phosphoric acid, nitric acid and the like, and hydrochloric acid and sulfuric acid are preferable. The amount of the mineral acid used is usually 1.0 to 10.0 mol, preferably 2.0 to 6.0 mol, and usually used as an aqueous solution, with respect to 1 mol of anilines (1). It is done.

  In addition, when such a diazotization reaction is performed using a mineral acid in the presence of an organic solvent, an organic solvent that is not miscible with water is usually used. Examples of the organic solvent include aliphatic hydrocarbons such as pentane, hexane, heptane, and petroleum ether; aromatic hydrocarbons such as benzene, toluene, and xylene; dichloromethane, chloroform, 1,2-dichloroethane, chlorobenzene, diethylene, and the like. And halogenated hydrocarbons such as chlorobenzene.

  The amount of the organic solvent used is usually 0.1 times by weight or more, preferably about 0.5 to about 5 times by weight of the anilines. In addition, the kind and usage-amount of the mineral acid used in this case are the same as those described above.

  Under the above conditions, when the diazotization reaction is performed using a mineral acid in the presence of an organic solvent, the aniline is uniformly dispersed in the aqueous solution of the mineral acid, so that the diazotization reaction proceeds at a high conversion rate, High purity phenylhydrazines are produced. As a result, highly pure phenyl triazolinones can be obtained in high yield.

  The subsequent reduction reaction of the diazonium salt obtained by diazotizing the aniline (1) is usually in the temperature range of 0 ° C. to 80 ° C., preferably 10 ° C. to 70 ° C. for 1 to 24 hours. The reaction is preferably performed under normal pressure for 2 to 12 hours.

  Examples of the sulfites that are reducing agents used in such a reduction reaction include ammonium sulfite, sodium sulfite, and potassium sulfite. Among these, sodium sulfite is preferable in view of high versatility.

  Examples of the bisulfites that are reducing agents used in such a reduction reaction include ammonium bisulfite, sodium bisulfite, and potassium bisulfite. Among these, sodium bisulfite is highly versatile. It is preferable in terms of the thickness.

  These may be used as they are, but are usually used as an aqueous solution. The amount of these sulfites or bisulfites used is usually 2.0 mol or more, preferably 2.5 to 4.0 mol, per 1 mol of anilines (1).

  The reaction is usually carried out by adding a diazonium salt obtained by diazotizing the aniline (1) to a solution in which the pH of an aqueous solution of sulfites or bisulfites is usually adjusted to 5.5 to 8.0. . The pH in the reaction system is usually adjusted to be in the range of 5.5 to 8.0, preferably in the range of 6.0 to 7.5. The pH can be adjusted with acids such as hydrochloric acid and sulfuric acid, or an alkaline aqueous solution such as sodium hydroxide, potassium hydroxide and ammonia.

  The hydrolysis performed following such a reduction reaction is usually in the temperature range of -5 ° C to 90 ° C, preferably 0 ° C to 80 ° C, for 1 to 24 hours, preferably 3 to 10 hours. Done under normal pressure.

  For such hydrolysis, a mineral acid is usually used, and examples thereof include hydrochloric acid, sulfuric acid, phosphoric acid, nitric acid, etc. Among them, hydrochloric acid and sulfuric acid are preferable. The amount of these mineral acids used is usually 2.0 moles or more, preferably 5.0-30.0 moles per mole of anilines (1) (moles of hydrogen chloride in hydrochloric acid). Number).

  The phenylhydrazines (2) can be used in the next second stage reaction as they are as the reaction mixture obtained by such hydrolysis, but are preferably used after neutralization with an alkali.

  Examples of the alkali include sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate and the like. Among these, sodium hydroxide is preferable in view of high versatility.

  In addition, the obtained phenylhydrazines (2) may be used in the next step as a mixture at this stage, and at this stage, any one of purification, isolation, and separation by removing the aqueous layer is performed. From the above, it may be used for the next step.

<Synthesis of formaldehyde-phenylhydrazone (3) (second stage)>
Next, in the “second stage” used in the first and second production methods of the phenyltriazolinones (5) of the present invention, the phenylhydrazines (2) and formaldehyde are added in the presence of a catalyst. The reaction is usually carried out in a solvent at pH 5 to 10, preferably pH 6 to 8, to produce the corresponding formaldehyde-phenylhydrazone (3).

  In such a reaction, the phenylhydrazines (2) obtained in the first step are purified and isolated, and formaldehyde is added to the reaction mixture without any treatment of separation by removing the aqueous layer. The reaction can be carried out efficiently.

  Such a second stage reaction is usually performed at a temperature ranging from −10 ° C. to the “boiling point of the solvent used”, preferably at a temperature of 0 ° C. to + 40 ° C., usually for 10 minutes to 24 hours, preferably For 30 minutes to 5 hours under normal pressure.

  In the reaction, the phenylhydrazines (2) and formaldehyde can be theoretically used (reacted) in equimolar amounts. Usually, 1 mol of phenylhydrazines (2) is 1. It is used in an amount of 0 to 2.0 mol, preferably 1.0 to 1.2 mol, and usually an aqueous formaldehyde solution containing such an amount of formaldehyde is used.

Moreover, as a catalyst used when making the said phenylhydrazine (2) and formaldehyde react, specifically, it is organic, such as ammonium formate, sodium formate, potassium formate, ammonium acetate, sodium acetate, potassium acetate, etc. Acid salts;
Organic acids such as formic acid and acetic acid; sulfonic acids such as p-toluenesulfonic acid;
Inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate;
And amines such as triethylamine, pyridine, 1,8-diazabicyclo [5,4,0] unde-7-ene;

These catalysts are generally used in an amount of 0.01 to 20.0 mol%, preferably 0.1 to 10.0 mol%, based on the phenylhydrazines (2).
In the second stage reaction, when the reaction is performed using the mixture containing the phenylhydrazines (2) obtained in the first stage, the phenylhydrazines (2) contained in the mixture The amount can be determined by analysis using high performance liquid chromatography or the like.

  The pH in the reaction system is usually adjusted to be in the range of 5 to 10, preferably 6 to 8. The pH can be adjusted with, for example, acids such as formic acid, acetic acid, hydrochloric acid and sulfuric acid, or an alkaline aqueous solution such as sodium hydroxide and potassium hydroxide.

It is preferable that the phenylhydrazines (2) and formaldehyde are reacted in the pH range from the viewpoint that side reactions can be suppressed.
Furthermore, examples of the solvent include water; alcohols such as methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol, methoxyethyl alcohol, n-butyl alcohol, sec-butyl alcohol, isobutyl alcohol, and t-butyl alcohol. Ethers such as tetrahydrofuran and dioxane; nitriles such as acetonitrile and propionitrile; and a mixed solvent of these and water can be used. Preferably, a mixed solvent of t-butyl alcohol and water is used. used.

  The mixed solvent may be a two-type mixed system or more. When a mixed solvent of an organic solvent and water is used, the organic solvent and water are usually in an amount of 1 to 500 parts by weight, preferably 10 to 200 parts by weight with respect to 100 parts by weight of the organic solvent. Used in parts.

These solvents are used in an amount of, for example, 100 g to 4000 g per 1 mol of the phenylhydrazines (2).
The amount of the solvent is the third stage, which is the reaction stage of the following formaldehyde-phenylhydrazones (3) and cyanic acid, or the fourth stage, which is the reaction stage of the following phenyltriazolidinones (4) and the oxidizing agent. It can be appropriately changed according to the reactants and reaction conditions at each stage, and is not generally determined.

  In addition, the obtained formaldehyde-phenylhydrazone (3) may be used in the next step as a mixture, and at this stage, after any treatment of purification, isolation, and separation by removing the aqueous layer is performed. You may use for the following process.

<Synthesis of Phenyltriazolidinones (4) (Stage 3)>
Next, in the “third stage” preferably used in the method for producing the phenyltriazolinones (5) of the present invention, the formaldehyde-phenylhydrazone (3) and cyanic acid are reacted in a solvent, Phenyltriazolidinones (4) are formed.

In such a third stage reaction, the formaldehyde-phenylhydrazone (3) obtained in the second stage is converted to cyanic acid without any purification, isolation or separation by aqueous layer removal. The reaction can be carried out efficiently. Further, the second stage resulting formaldehyde - phenyl hydrazones (3) formaldehyde from the reaction mixture containing the - phenyl hydrazones a (3), purified, after separation Ri by the removal of the isolation or aqueous layer The reaction after the third stage can also be performed.

  When the reaction in the third stage is performed using the mixture containing the formaldehyde-phenylhydrazone (3) obtained in the second stage, the formaldehyde-phenylhydrazone (3) contained in the mixture. The amount of can be determined by analysis using high performance liquid chromatography or the like.

This third stage reaction is usually carried out at a temperature of −10 ° C. to + 60 ° C., preferably 0 ° C. to + 30 ° C., usually 1 to 24 hours, preferably 1 to 5 hours, under normal pressure.
The formaldehyde-phenylhydrazones (3) and cyanic acid may theoretically be used in equimolar amounts, but usually cyanic acid is 1 per mole of formaldehyde-phenylhydrazones (3). It is used in an amount of 0.0 to 3.0 mol, preferably 1.0 to 2.0 mol.

As the solvent, the same solvent as used in the second step is used from the viewpoint of handling efficiency.
When a mixed solvent of an organic solvent and water is used , the organic solvent and water are usually in an amount of 1 to 500 parts by weight, preferably 10 to 200 parts by weight with respect to 100 parts by weight of the organic solvent. Used in parts.

These solvents are used in an amount of 100 g to 5000 g per mol of formaldehyde-phenylhydrazone (3).
In addition, the phenyltriazolidinones (4) obtained in the third stage may be purified and isolated as necessary, but are usually used in the fourth stage as a mixture.

<Synthesis of Phenyltriazolinones (5) (Fourth Stage)>
Next, in the method for producing phenyltriazolinones (5) of the present invention, in this “fourth stage”, an oxidizing agent selected from hypohalite and oxygen, and the above-mentioned phenyltriazolidinones (4) is reacted in a solvent in the absence of a catalyst or in the presence of an oxidation catalyst to form the desired phenyltriazolinones (5).

  The phenyltriazolidinones (4) obtained in the third stage are usually used in the fourth stage as they are in a mixture containing the phenyltriazolidinones (4) without being isolated and purified. Is done. For this reason, such a reaction can be efficiently performed by adding an oxidizing agent to the reaction mixture containing the phenyltriazolidinones (4) obtained in the third stage.

This fourth stage reaction is usually carried out at a temperature of -20 to 60 ° C, preferably 0 ° C to 30 ° C, usually 1 to 24 hours, preferably 2 to 8 hours under normal pressure.
Examples of the hypohalite that is the oxidizing agent include sodium hypochlorite, potassium hypochlorite, calcium hypochlorite, sodium hypobromite, potassium hypobromite, and the like. Among these, sodium hypochlorite is preferable from the viewpoint of versatility.

The above hypohalite can also be used in the presence of an oxidation catalyst, if necessary.
Examples of the oxidation catalyst used include ferrous chloride, ferric chloride, ferrous bromide, ferric bromide, ferrous sulfate, ferric sulfate, cobalt chloride, cobalt bromide, Iron group salts such as cobalt sulfate, cobalt nitrate, cobalt acetate, nickel chloride;
Iron group complexes such as iron (III) acetylacetonate, cobalt (II) acetylacetonate, cobalt (II) bis (salicylidene) ethylenediamine, hexaamminenickel (II) chloride;
Platinum group such as platinum and palladium;
Platinum group salts such as palladium chloride, palladium acetate, platinum oxide;
Platinum group complexes such as chloro (triphenylphosphine) rhodium, dichlorobis (triphenylphosphine) ruthenium;
Copper salts such as copper (I) chloride, copper (I) bromide, copper (II) chloride, copper (II) bromide, copper sulfate, copper acetate;
Copper complexes such as copper (II) acetylacetonate and bisethylenediamine copper;
Zinc salts such as zinc chloride;
Zinc complexes such as tris (ethylenediamine) zinc;
Vanadium salts such as divanadium pentoxide;
Vanadium complexes such as vanadium oxide acetylacetonate;
And rare earth salts such as cerium chloride and samarium iodide.

These catalysts may be used alone or in combination of two or more.
In the reaction, the above phenyltriazolidinones (4) and the oxidizing agent may theoretically be used in equimolar amounts, but usually the amount is 1 mol of phenyltriazolidinones (4). The oxidizing agent is usually used in an amount of 1.0 to 1.4 mol, preferably 1.0 to 1.1 mol.

  Specifically, for example, an aqueous solution of sodium hypochlorite having a concentration of 5 to 25% (weight / weight), preferably 5 to 15% can be used. Moreover, the said oxidation catalyst used as needed is 0.01-10.0 mol% normally with respect to phenyl triazolidinone (4), Preferably it is the quantity of 0.1-1.0 mol%. used.

  When the reaction in the fourth stage is performed using the mixture containing the phenyltriazolidinones (4) obtained in the third stage, the amount of the phenyltriazolidinones (4) in the mixture is It can be determined by analysis using high performance liquid chromatography or the like.

  As the solvent, the same solvents as those used in the second stage and the third stage are used, and even in the case of a mixed solvent of an organic solvent and water, they are used at the same mixing ratio. Such a solvent is used in an amount of 100 g to 6000 g per mol of phenyltriazolidinones (4).

In the method for producing phenyltriazolinones (5) of the present invention, the reaction solution is preferably stirred at least gently in each of the first to fourth steps.
After completion of the reaction, the organic solvent in the mixed solvent used (a mixed solvent of an organic solvent and water) can be reused by being distilled off from the reaction mixture and recovered using a distillation apparatus or the like.

  The target phenyltriazolinones (5) can be isolated by ordinary extraction / separation, or after the organic solvent is distilled off, the target (5) is precipitated in water and filtered. Is done.

Another method for isolating and purifying the target phenyltriazolinones (5) is, for example, the following method.
That is, after distilling off the organic solvent in the reaction mixture, the target phenyltriazolinones (5) are dissolved in an aqueous solution of a base such as sodium hydroxide to form a salt, which is washed with the organic solvent. .

  Next, a mineral acid such as hydrochloric acid is added to the washed solution of the phenyltriazolinone (5) salt to neutralize the phenyltriazolinone (5) salt-containing solution. Phenyltriazolinones (5) are precipitated.

High-purity phenyltriazolinones (5) can be obtained by filtering and washing the precipitated crystals with water.
Another method for isolating and purifying the target phenyltriazolinones (5) is, for example, the following method.

  That is, after completion of the reaction, first, alkali is added to the reaction mixture to form an alkali salt of the target phenyltriazolinones (5), and at the same time, an alkali treatment is performed to decompose the reaction by-product. Next, when a mixed solvent of an organic solvent and water is used as a reaction solvent, the organic solvent is distilled off, and then an aqueous mixture containing an alkali salt of the target phenyltriazolinones (5) and impurities. Is washed with an organic solvent to remove impurities from the aqueous mixture without loss of the desired product.

  Next, a mineral acid such as hydrochloric acid is added to an alkali salt-containing aqueous solution of phenyltriazolinones (5) washed with an organic solvent to neutralize the alkali salt-containing aqueous solution of phenyltriazolinones (5). As a result, the target phenyltriazolinones (5) are precipitated.

High-purity phenyltriazolinones (5) can be obtained by filtering and washing the precipitated crystals with water.
Such an alkali treatment is usually performed at a temperature of 0 ° C. to 100 ° C., preferably 20 ° C. to 90 ° C., usually 1 to 24 hours, preferably 1 to 12 hours, under normal pressure.

  Examples of the alkali used include sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate and the like. Among these, sodium hydroxide is preferable in view of high versatility. Such an alkali is usually used in an amount of 1.2 to 4.0 mol, preferably 2.0 to 2.5 mol, per 1 mol of phenyltriazolinones (5).

  Examples of the organic solvent used for the washing include aliphatic hydrocarbons such as pentane, hexane, heptane and petroleum ether; aromatic hydrocarbons such as benzene, toluene and xylene; diethyl ether, diisopropyl ether, t- Ethers such as butyl methyl ether; halogenated hydrocarbons such as dichloromethane, chloroform, 1,2-dichloroethane, chlorobenzene, and dichlorobenzene.

  When the phenyltriazolinones (5) are isolated and purified under the above conditions, the reaction by-product is decomposed by alkali. Therefore, the target mixture is lost by washing the aqueous mixture after the alkali treatment with an organic solvent. Impurities can be removed without accompanying, and high-purity phenyltriazolinones can be obtained in high yield.

The obtained target product may be further purified using means such as washing with an organic solvent, column chromatography, or recrystallization as necessary.
The phenyltriazolinones (5) thus obtained are suitably used as agricultural chemicals, raw materials for producing pharmaceuticals, and the like.

  In the present invention, the phenylhydrazines represented by the above general formula (2), which are intermediate products, or the formaldehyde-phenylhydrazones represented by the above general formula (3), which are intermediate products, The whole process can be carried out without treating the phenyltriazolidinones represented by the above general formula (4), which are body products, by any method of purification, isolation and separation by removing the aqueous layer.

  In each of the above steps, the intermediate product is a phenylhydrazine represented by the general formula (2), the intermediate product is a formaldehyde-phenylhydrazone represented by the general formula (3), or an intermediate product. After the phenyl triazolidinones represented by the above general formula (4), which are product products, are treated by any of the methods of purification, isolation and separation by removing the aqueous layer as necessary, each step is carried out You can also.

  In this case, only one of the phenylhydrazines, the formaldehyde-phenylhydrazones, and the phenyltriazolidinones may be treated by any one of the above methods, and two kinds may be treated by any one of the above methods. Alternatively, all three types may be processed by any one of the methods described above.

  In each of the above steps, the solvent does not adversely affect the reaction, and preferably anilines (1), phenylhydrazines (2), formaldehyde-phenylhydrazones (3) and phenyltriazolidinones (4) Solvents that can be satisfactorily dissolved in any of the above are preferable in the reaction operation, but the above-mentioned solvents that can dissolve or mix at least partly any of these are used.

  According to the production method of the present invention, a high-purity target compound (in a short time under the above-mentioned relatively low reaction conditions and through a series of reactions consisting of the above-mentioned first to fourth stages) Phenyltriazolinones (5)) can be obtained in high yield.

  EXAMPLES Hereinafter, although this invention is demonstrated further more concretely based on an Example, this invention is not restrict | limited at all by these Examples.

[Example 1]
<Production of 1- (2,4-dichlorophenyl) -1,2,4-triazol-5-one>
A 1 L 4-necked flask is equipped with a stirrer, thermometer, and Dimroth condenser. Into a reaction vessel, add 330 g of 10% hydrochloric acid and 48.6 g of 2,4-dichloroaniline (purity> 99%), and stir at 30 ° C. for 15 minutes. did.

The obtained mixture was cooled to −5 ° C., and 63 g of 35% aqueous sodium nitrite solution was added dropwise over 30 minutes, followed by stirring at −3 to 0 ° C. for 1 hour to obtain a diazonium salt solution.
A reaction vessel was prepared by attaching a stirrer, a thermometer, and a Dimroth condenser to a 2 L four-necked flask separate from the above vessel. In this reaction vessel, 97.4 g of sodium sulfite (purity 97%) was dissolved in 350 g of water, and 95% sulfuric acid was added to adjust the pH to 7.2.

This solution was cooled to 10 ° C., and the previously prepared diazonium salt solution was quickly added.
The obtained mixture was heated to 20 ° C. over 30 minutes, then heated to 65 ° C. and stirred at the same temperature for 2 hours to reduce the diazonium salt, and a mixture containing 2,4-dichlorophenylhydrazine sulfonate was obtained. Obtained.

200 g of toluene was added to the obtained mixture, and the mixture was stirred at 65 ° C. for 15 minutes to wash the aqueous layer to remove unreacted raw materials and reaction byproducts, and then the mixture was allowed to stand for liquid separation.
The separated aqueous layer was placed in a reaction vessel equipped with a stirrer, a thermometer, and a Dimroth condenser in a 3 L four-necked flask. Next, 313 g of 35% hydrochloric acid was added dropwise at 20 ° C. over 20 minutes. The mixture was stirred at 0 ° C. for 3 hours to hydrolyze 2,4-dichlorophenylhydrazine sulfonate to obtain a mixture containing hydrochloride of 2,4-dichlorophenylhydrazine.

  The mixture is cooled to 10 ° C., 300 g of 50% aqueous sodium hydroxide is slowly added to precipitate 2,4-dichlorophenylhydrazine, and then filtered to remove the aqueous layer to remove crude 2,4-dichlorophenylhydrazine. Got.

The obtained 2,4-dichlorophenylhydrazine crude product was 55 g. (Purity 90%).
Charge a crude vessel of 2,4-dichlorophenylhydrazine obtained in a reaction vessel equipped with a stirrer, thermometer, and Dimroth condenser to a 1 L four-necked flask, followed by 300 g of tertiary butanol, 50 g of water, sodium acetate 2 0.5 g was added, and 27.5 g of 36% formaldehyde aqueous solution was added dropwise over 10 minutes while maintaining the pH of the mixture at 6 ° C. at 20 ° C. over 10 minutes, followed by stirring at the same temperature and in the same pH range for 2 hours. A mixture containing 2,4-dichlorophenylhydrazone was obtained.

The reaction mixture was cooled to 10 ° C., 19.4 g of cyanic acid was added, and the mixture was stirred at the same temperature for 4 hours to obtain a mixture containing 2,4-dichlorophenyltriazolidinone.
After removing the unreacted formaldehyde and salts by removing the aqueous layer from the separated two layers (organic layer and aqueous layer), the resulting organic layer (tertiary butanol layer) is subjected to 11% 162.5 g of sodium chlorite aqueous solution was added dropwise over 30 minutes.

After the dropwise addition, the mixture was stirred at 10 ° C. for 1 hour and further stirred at 25 ° C. for 5 hours to obtain a mixture containing the title target substance.
Sodium hydroxide 24g was added to the aqueous layer after the tertiary butanol was distilled off to form the salt of the title target substance and dissolved in the aqueous layer, and then 100g of toluene was added and stirred to wash the aqueous layer. The reaction by-product was removed from the aqueous layer, and the mixture was allowed to stand for liquid separation.

  The aqueous layer obtained by the liquid separation was cooled to 15 ° C., and 94 g of 35% hydrochloric acid was added dropwise over 15 minutes to neutralize the aqueous layer to release the title target substance and to precipitate crystals Was collected by filtration and washed with 200 g of water.

The crystals were sufficiently dried in a vacuum dryer to obtain 63.5 g (yield 92%, purity 97%) of the title target compound. The melting point was 190 to 191 ° C. EI-MS: M ⁺ 229.

[Example 2]
<Production of 1- (2,4-dichlorophenyl) -1,2,4-triazol-5-one>
A 1 L 4-necked flask is equipped with a stirrer, thermometer, and Dimroth condenser. Into a reaction vessel, add 330 g of 10% hydrochloric acid and 48.6 g of 2,4-dichloroaniline (purity> 99%), and stir at 30 ° C. for 15 minutes. did.

The obtained mixture was cooled to −5 ° C., and 63 g of 35% aqueous sodium nitrite solution was added dropwise over 30 minutes, followed by stirring at −3 to 0 ° C. for 1 hour to obtain a diazonium salt solution.
A reaction vessel was prepared by attaching a stirrer, a thermometer, and a Dimroth condenser to a 2 L four-necked flask different from the above vessel. In this reaction vessel, 97.4 g of sodium sulfite (purity 97%) was dissolved in 350 g of water, and 95% sulfuric acid was added to adjust the pH to 7.2.

This solution was cooled to 10 ° C., and the previously prepared diazonium salt solution was quickly added.
The obtained mixture was heated to 20 ° C. over 30 minutes, then heated to 65 ° C. and stirred at the same temperature for 2 hours to reduce the diazonium salt, and a mixture containing 2,4-dichlorophenylhydrazine sulfonate was obtained. Obtained.

200 g of toluene was added to the obtained mixture, and the mixture was stirred at 65 ° C. for 15 minutes to wash the aqueous layer, and unreacted raw materials and reaction byproducts were removed from the aqueous layer, followed by liquid separation.
The aqueous layer recovered by liquid separation was placed in a reaction vessel equipped with a stirrer, thermometer, and Dimroth condenser in a 3 L four-necked flask, and 313 g of 35% hydrochloric acid was added dropwise at 20 ° C. over 20 minutes. The mixture was stirred at 75 ° C. for 3 hours to hydrolyze 2,4-dichlorophenylhydrazine sulfonate to obtain a mixture containing hydrochloride of 2,4-dichlorophenylhydrazine.

  The mixture is cooled to 10 ° C., 300 g of 50% aqueous sodium hydroxide is slowly added to precipitate 2,4-dichlorophenylhydrazine and then filtered to remove the aqueous layer to remove 2,4-dichlorophenylhydrazine. A crude product was obtained.

The obtained 2,4-dichlorophenylhydrazine crude product was 55 g (purity 90%).
A 2,4-dichlorophenylhydrazine crude product obtained in a reaction vessel equipped with a stirrer, thermometer and Dimroth condenser in a 1 L four-necked flask was charged, followed by 300 g of tertiary butanol, 50 g of water, and sodium acetate. 2.5 g was added, and 27.5 g of 36% formaldehyde aqueous solution was added dropwise over 10 minutes while maintaining the pH at 6 to 8 at 20 ° C., followed by stirring at the same temperature and the same pH range for 2 hours. , 4-dichlorophenylhydrazone was obtained.

  The obtained reaction mixture was cooled to 10 ° C., 19.4 g of cyanic acid was added, stirred at the same temperature for 4 hours, and the aqueous layer was removed from the separated two layers (organic layer and aqueous layer). The formaldehyde and salts of the reaction were removed.

  Subsequently, 180 mg of copper (II) acetate monohydrate was added to the obtained organic layer (tertiary butanol), and oxygen gas was introduced into the reaction mixture at a flow rate of 10 ml / min from an oxygen cylinder at 10 ° C. The mixture was stirred for 8 hours and further stirred at 25 ° C. for 5 hours to obtain a mixture containing the title target substance.

24 g of sodium hydroxide and 100 g of toluene were added to the aqueous layer after the tertiary butanol had been distilled off, and the mixture was stirred to wash the aqueous layer. After removing the side reaction products, the mixture was left to separate.
The separated aqueous layer was cooled to 15 ° C., and 94 g of 35% hydrochloric acid was added dropwise over 15 minutes to neutralize the aqueous layer to release the title target substance, and the precipitated crystals were collected by filtration. Washed with water.

The obtained crystals were sufficiently dried in a vacuum dryer to obtain 64.2 g (yield: 93%, purity: 96%) of the target compound. The melting point was 190 to 191 ° C. EI-MS: M ⁺ 229.

[Example 3]
<Production of 1- (2,4-dichlorophenyl) -1,2,4-triazol-5-one>
A 1 L 4-necked flask is equipped with a stirrer, thermometer, and Dimroth condenser. Into a reaction vessel, add 330 g of 10% hydrochloric acid and 48.6 g of 2,4-dichloroaniline (purity> 99%), and stir at 30 ° C. for 15 minutes. did.

The obtained mixture was cooled to −5 ° C., and 63 g of 35% aqueous sodium nitrite solution was added dropwise over 30 minutes, followed by stirring at −3 to 0 ° C. for 1 hour to obtain a diazonium salt solution.
A reaction vessel was prepared by attaching a stirrer, a thermometer, and a Dimroth condenser to a 2 L four-necked flask separate from the above vessel. In this reaction vessel, 97.4 g of sodium sulfite (purity 97%) was dissolved in 350 g of water, and 95% sulfuric acid was added to adjust the pH to 7.2.

This solution was cooled to 10 ° C., and the previously prepared diazonium salt solution was quickly added.
The obtained mixture was heated to 20 ° C. over 30 minutes, then heated to 65 ° C. and stirred at the same temperature for 2 hours to reduce the diazonium salt, and a mixture containing 2,4-dichlorophenylhydrazine sulfonate was obtained. Obtained. To the resulting mixture, 200 g of toluene was added, and the mixture was stirred at 65 ° C. for 15 minutes to wash the aqueous layer. Unreacted raw materials and reaction byproducts were removed from the aqueous layer, and then the mixture was allowed to stand for separation.

  The separated aqueous layer was placed in a 3 L four-necked flask in a reaction vessel equipped with a stirrer, thermometer and Dimroth condenser, and 313 g of 35% hydrochloric acid was added dropwise at 20 ° C. over 20 minutes. The mixture was stirred for a period of time to hydrolyze the previously obtained 2,4-dichlorophenylhydrazine sulfonate to obtain a mixture containing hydrochloride of 2,4-dichlorophenylhydrazine.

  The mixture was cooled to 10 ° C., 300 g of 50% aqueous sodium hydroxide was slowly added to precipitate 2,4-dichlorophenylhydrazine, and an aqueous 2,4-dichlorophenylhydrazine suspension was obtained.

  Next, 2.5 g of sodium acetate was added to this suspension, and 27.5 g of a 36% formaldehyde aqueous solution was added dropwise over 10 minutes while maintaining the pH of the mixture at 6 to 8 at 20 ° C. Stir for 2 hours in the range. Subsequently, the crude product of formaldehyde-2,4-dichlorophenylhydrazone was obtained by filtering from the reaction mixture and removing the aqueous layer. The obtained formaldehyde-2,4-dichlorophenylhydrazone crude product was 58 g (purity 90%).

  Next, the crude product of formaldehyde-2,4-dichlorophenylhydrazone obtained in a reaction vessel equipped with a stirrer, a thermometer, and a Dimroth condenser was added to a 1 L four-necked flask, and 300 g of tertiary butanol was added to the mixture. Was cooled to 10 ° C., 19.4 g of cyanic acid was added, and the mixture was stirred at the same temperature for 4 hours to obtain a mixture containing 2,4-dichlorophenyltriazolidinone.

Next, 162.5 g of an 11% aqueous sodium hypochlorite solution was added dropwise over 30 minutes to the resulting mixture at the same temperature.
After the dropwise addition, the mixture was stirred at 10 ° C. for 1 hour and further stirred at 25 ° C. for 5 hours to obtain a mixture containing the title target substance.

  After the tertiary butanol has been distilled off, 50 g of water and 24 g of sodium hydroxide are added to the aqueous layer to form the salt of the title target substance, which is dissolved in the aqueous layer. The layer was washed to remove side reaction products from the aqueous layer, and then allowed to stand for liquid separation.

  The aqueous layer recovered by liquid separation is cooled to 15 ° C., and 94 g of 35% hydrochloric acid is added dropwise over 15 minutes to neutralize the aqueous layer to release the title target substance, and the precipitated crystals are filtered. Collected and washed with 200 g of water.

The obtained crystals were sufficiently dried in a vacuum dryer to obtain 62.1 g (yield 90%, purity 96%) of the title target compound. The melting point was 190 to 191 ° C. EI-MS: M ⁺ 229.

[Example 4]
<Production of 1-phenyl-1,2,4-triazol-5-one>
A 1 L four-necked flask was equipped with a stirrer, thermometer, and Dimroth condenser to give a reaction vessel, 330 g of 10% hydrochloric acid and 27.9 g of aniline (purity> 99%) were added, and the mixture was stirred at 30 ° C. for 15 minutes.

The obtained mixture was cooled to −5 ° C., and 63 g of 35% aqueous sodium nitrite solution was added dropwise over 30 minutes, followed by stirring at −3 to 0 ° C. for 1 hour to obtain a diazonium salt solution.
A reaction vessel was prepared by attaching a stirrer, a thermometer, and a Dimroth condenser to a 2 L four-necked flask separate from the above vessel. In this reaction vessel, 97.4 g of sodium sulfite (purity 97%) was dissolved in 350 g of water, and 95% sulfuric acid was added to adjust the pH to 7.2.

This solution was cooled to 10 ° C., and the previously prepared diazonium salt solution was quickly added.
The obtained mixture was heated to 20 ° C. over 30 minutes and then heated to 65 ° C. and stirred at the same temperature for 2 hours to reduce the diazonium salt to obtain a mixture containing phenylhydrazine sulfonate.

200 g of toluene was added to the obtained mixture, and the mixture was stirred at 65 ° C. for 15 minutes to wash the aqueous layer, and unreacted raw materials and reaction byproducts were removed from the aqueous layer.
The separated aqueous layer was placed in a reaction vessel equipped with a stirrer, a thermometer, and a Dimroth condenser in a 3 L four-necked flask. Next, 313 g of 35% hydrochloric acid was added dropwise at 20 ° C. over 20 minutes. The mixture was stirred at 0 ° C. for 3 hours to hydrolyze the previously obtained phenylhydrazine sulfonate to obtain a mixture containing phenylhydrazine hydrochloride.

  The mixture was cooled to 10 ° C., 300 g of 50% aqueous sodium hydroxide was slowly added to precipitate phenylhydrazine, and then the aqueous layer was removed by filtration to recover the crude phenylhydrazine product. It was.

The obtained phenylhydrazine crude product was 34 g (purity 90%).
Charge a crude phenylhydrazine product obtained in a reaction vessel equipped with a stirrer, thermometer, and Dimroth condenser into a 1 L four-necked flask, and then add 300 g of tertiary butanol, 50 g of water, and 2.5 g of sodium acetate. In addition, 27.5 g of a 36% formaldehyde aqueous solution was added dropwise over 10 minutes while maintaining the pH of the mixture at 6 to 8 at 20 ° C., followed by stirring at the same temperature and in the same pH range for 2 hours to formaldehyde-phenylhydrazone. A mixture containing was obtained.

The obtained reaction mixture was cooled to 10 ° C., 19.4 g of cyanic acid was added, and the mixture was stirred at the same temperature for 4 hours to obtain a mixture containing phenyltriazolidinone.
Next, 162.5 g of an 11% aqueous sodium hypochlorite solution was added dropwise over 30 minutes to the resulting mixture at the same temperature.

After the dropwise addition, the mixture was stirred at 10 ° C. for 1 hour and further stirred at 25 ° C. for 5 hours to obtain a mixture containing the title target substance.
Sodium hydroxide 24g was added to the aqueous layer after the tertiary butanol was distilled off to form the salt of the title target substance and dissolved in the aqueous layer, and then 100g of toluene was added and stirred to wash the aqueous layer. Then, the reaction by-product was removed from the aqueous layer, and then allowed to stand for liquid separation.

  The aqueous layer obtained by liquid separation was cooled to 15 ° C., and 94 g of 35% hydrochloric acid was added dropwise over 15 minutes to neutralize the aqueous layer to release the title target substance, and the precipitated crystals were filtered. And washed with 150 g of water.

The obtained crystals were sufficiently dried with a vacuum dryer to obtain 42.5 g (yield 88%, purity 96%) of the title compound. The melting point was 184 to 185 ° C. EI-MS: M ^<+> 161.

[Example 5]
<Production of 1- (2,3-dimethylphenyl) -1,2,4-triazol-5-one>
A 1 L 4-neck flask equipped with a stirrer, thermometer, and Dimroth condenser is used as a reaction vessel. Add 330 g of 10% hydrochloric acid and 36.3 g of 2,3-dimethylaniline (purity> 99%), and stir at 30 ° C. for 15 minutes. did.

The obtained mixture was cooled to −5 ° C., and 63 g of 35% aqueous sodium nitrite solution was added dropwise over 30 minutes, followed by stirring at −3 to 0 ° C. for 1 hour to obtain a diazonium salt solution.
Separately from the above vessel, a 5 L four-necked flask is equipped with a stirrer, thermometer and Dimroth condenser to make a reaction vessel. Dissolve 97.4 g of sodium sulfite (purity 97%) in 350 g of water and add 95% sulfuric acid. The pH was adjusted to 7.2.

  This solution was cooled to 10 ° C., and the previously prepared diazonium salt solution was quickly added. The mixture was heated to 20 ° C. over 30 minutes and then heated to 65 ° C. and stirred at the same temperature for 2 hours to reduce the diazonium salt to obtain a reaction mixture containing 2,3-dimethylphenylhydrazine sulfonate. It was.

  The obtained reaction mixture was cooled to 20 ° C., and 313 g of 35% hydrochloric acid was added dropwise over 20 minutes, followed by stirring at 75 ° C. for 3 hours to hydrolyze the previously obtained 2,3-dimethylphenylhydrazine sulfonate. Decomposition gave a mixture containing hydrochloride of 2,3-dimethylphenylhydrazine.

  The obtained mixture was cooled to 10 ° C., 300 g of 50% aqueous sodium hydroxide was slowly added to precipitate 2,3-dimethylphenylhydrazine, and an aqueous 2,3-dimethylphenylhydrazine suspension was obtained.

  Then, 1,500 g of tertiary butanol and 2.5 g of sodium acetate were added to the resulting aqueous suspension of 2,3-dimethylphenylhydrazine, and 36% while maintaining the pH of the mixture at 6-8 at 20 ° C. After 27.5 g of an aqueous formaldehyde solution was added dropwise over 10 minutes, the mixture was stirred at the same temperature and the same pH range for 2 hours to obtain a mixture containing formaldehyde-2,3-dimethylphenylhydrazone.

The reaction mixture was cooled to 10 ° C., 19.4 g of cyanic acid was added, and the mixture was stirred at the same temperature for 4 hours to obtain a mixture containing 2,3-dimethylphenyltriazolidinone.
After removing the unreacted formaldehyde and salts by removing the aqueous layer from the separated two layers (organic layer and aqueous layer), the resulting organic layer (tertiary butanol layer) is subjected to 11% 162.5 g of sodium chlorite aqueous solution was added dropwise over 30 minutes.

After the dropwise addition, the mixture was stirred at 10 ° C. for 1 hour and further stirred at 25 ° C. for 5 hours to obtain a mixture containing the title target substance.
Sodium hydroxide 24g was added to the aqueous layer after the tertiary butanol was distilled off to form the salt of the title target substance and dissolved in the aqueous layer, and then 100g of toluene was added and stirred to wash the aqueous layer. And then left to separate.

  The separated aqueous layer was cooled to 15 ° C., and 94 g of 35% hydrochloric acid was added dropwise over 15 minutes to neutralize the aqueous layer to release the title target substance. The precipitated crystals were collected by filtration, and 150 g Washed with water.

The obtained crystals were sufficiently dried in a vacuum dryer to obtain 51.6 g (yield 91%, purity 95%) of the title target compound. The melting point was 191-192 ° C. EI-MS: M ⁺ 189.

[Example 6]
<Production of 1- (2,4-dichlorophenyl) -1,2,4-triazol-5-one>
A 5-L four-necked flask equipped with a stirrer, thermometer, and Dimroth condenser was used as a reaction vessel. After adding 350.0 g of 2,4-dichloroaniline (purity> 99%) and 350 g of toluene, the mixture was stirred at 30 ° C. for 15 minutes. 2353 g of 10% hydrochloric acid was added, and the mixture was further stirred at 30 ° C. for 15 minutes.

The obtained mixture was cooled to −5 ° C., 452 g of 35% aqueous sodium nitrite solution was added dropwise over 30 minutes, and then stirred at −3 to 0 ° C. for 1 hour to obtain a diazonium salt solution.
Separately from the above vessel, a 10 L four-necked flask was equipped with a stirrer, thermometer, and Dimroth condenser to prepare a reaction vessel. In this reaction vessel, 698.9 g of sodium sulfite (purity 97%) was dissolved in 2796 g of water, and 22.2 g of 95% sulfuric acid was added to adjust the pH to 7.2.

The solution was cooled to 10 ° C., and the previously prepared diazonium salt solution was added over 5 minutes.
The obtained mixture was heated to 20 ° C. over 30 minutes, then heated to 65 ° C. and stirred at the same temperature for 2 hours to reduce the diazonium salt, and a mixture containing 2,4-dichlorophenylhydrazine sulfonate was obtained. Obtained.

The obtained mixture was allowed to stand to separate a toluene layer and an aqueous layer, thereby removing unreacted raw materials and reaction byproducts contained in the toluene layer.
The separated aqueous layer was put into a reaction vessel equipped with a stirrer, a thermometer, and a Dimroth condenser in a 10 L capacity four-necked flask, and then 2241 g of 35% hydrochloric acid was added dropwise at 20 ° C. over 30 minutes. The mixture was stirred at 0 ° C. for 3 hours to hydrolyze 2,4-dichlorophenylhydrazine sulfonate to obtain a mixture containing hydrochloride of 2,4-dichlorophenylhydrazine.

  The mixture was cooled to 10 ° C., 2241 g of 48% aqueous sodium hydroxide solution was added dropwise over 30 minutes to precipitate 2,4-dichlorophenylhydrazine, and then filtered to remove the aqueous layer to remove 2,4-dichlorophenyl. A crude hydrazine product was obtained.

The obtained 2,4-dichlorophenylhydrazine crude product was 900 g. (Purity 98%).
Charge the obtained 2,4-dichlorophenylhydrazine crude product to a reaction vessel equipped with a stirrer, thermometer, and Dimroth condenser in a 10 L capacity four-necked flask, and then add 1904 g of tertiary butanol and 1500 g of water. While maintaining the pH of the mixture at 6 to 8 at 20 ° C., 174.6 g of 37% aqueous formaldehyde solution was added dropwise over 15 minutes. Next, a solution obtained by dissolving 8.8 g of sodium acetate and 2.6 g of acetic acid in 44 g of water was dropped into the obtained mixture over 5 minutes at 20 ° C., and then the pH of the mixture was adjusted to 5.5 to 6 at 20 ° C. While maintaining, the mixture was stirred for 2 hours to obtain a mixture containing formaldehyde-2,4-dichlorophenylhydrazone.

Next, the reaction mixture was cooled to 10 ° C., 130.1 g of cyanic acid was added, and the mixture was stirred at the same temperature for 4 hours to obtain a mixture containing 2,4-dichlorophenyltriazolidinone.
To the resulting mixture, 1441 g of a 10% aqueous sodium hypochlorite solution was added dropwise over 45 minutes so that the temperature of the mixture did not exceed 10 ° C. After dropping, the mixture was stirred at 10 ° C. for 1 hour and further stirred at 25 ° C. for 5 hours to obtain a mixture containing the title target compound.

  Next, 359 g of a 48% aqueous sodium hydroxide solution was added to the obtained mixture, and the mixture was stirred at 80 ° C. for 2 hours. Then, tertiary butanol was distilled off from the mixture. After 990 g of dichloroethane was added to an aqueous mixture containing the sodium salt of the title compound and impurities and the mixture was stirred and washed to remove impurities from the aqueous layer, the mixture was allowed to stand and separated. The aqueous layer containing the sodium salt of the title target compound obtained by liquid separation was cooled to 20 ° C., and 1660 g of 18% hydrochloric acid was added dropwise over 60 minutes to neutralize the water layer and The compound was released and the precipitated crystals were collected by filtration and washed with 2000 g of water.

The obtained crystals were sufficiently dried in a vacuum drier to obtain 472 g (yield 95%, purity 99%) of the title target compound. The melting point was 190 to 191 ° C. EI-MS: M ⁺ 229.

[Example 7]
<Production of 1- (2,4-dichlorophenyl) -1,2,4-triazol-5-one>
A 5-L four-necked flask equipped with a stirrer, thermometer, and Dimroth condenser was used as a reaction vessel. After adding 350.0 g of 2,4-dichloroaniline (purity> 99%) and 350 g of toluene, the mixture was stirred at 30 ° C. for 15 minutes. 2353 g of 10% hydrochloric acid was added, and the mixture was further stirred at 30 ° C. for 15 minutes.

The obtained mixture was cooled to −5 ° C., 452 g of 35% aqueous sodium nitrite solution was added dropwise over 30 minutes, and then stirred at −3 to 0 ° C. for 1 hour to obtain a diazonium salt solution.
Separately from the above vessel, a 10 L four-necked flask was equipped with a stirrer, thermometer, and Dimroth condenser to prepare a reaction vessel. In this reaction vessel, 698.9 g of sodium sulfite (purity 97%) was dissolved in 2796 g of water, and 22.2 g of 95% sulfuric acid was added to adjust the pH to 7.2.

The solution was cooled to 10 ° C., and the previously prepared diazonium salt solution was added over 5 minutes.
The obtained mixture was heated to 20 ° C. over 30 minutes, then heated to 65 ° C. and stirred at the same temperature for 2 hours to reduce the diazonium salt, and a mixture containing 2,4-dichlorophenylhydrazine sulfonate was obtained. Obtained.

The obtained mixture was allowed to stand to separate a toluene layer and an aqueous layer, thereby removing unreacted raw materials and reaction byproducts contained in the toluene layer.
The separated aqueous layer was put into a reaction vessel equipped with a stirrer, a thermometer, and a Dimroth condenser in a 10 L capacity four-necked flask, and then 2241 g of 35% hydrochloric acid was added dropwise at 20 ° C. over 30 minutes. The mixture was stirred at 0 ° C. for 3 hours to hydrolyze 2,4-dichlorophenylhydrazine sulfonate to obtain a mixture containing hydrochloride of 2,4-dichlorophenylhydrazine.

  The mixture was cooled to 10 ° C., and 2241 g of 48% aqueous sodium hydroxide solution was added dropwise over 30 minutes to precipitate 2,4-dichlorophenylhydrazine to obtain an aqueous 2,4-dichlorophenylhydrazine suspension.

  Next, 174.6 g of a 37% aqueous formaldehyde solution was added dropwise to the suspension over 15 minutes while maintaining the pH of the mixture at 6 to 8 at 20 ° C. A solution prepared by dissolving 8.8 g of sodium acetate and 2.6 g of acetic acid in 44 g of water was dropped into the obtained mixture at 20 ° C. over 5 minutes, and then the pH of the mixture was maintained at 5.5 to 6 at 20 ° C. The mixture was stirred for 2 hours. Subsequently, the crude product of formaldehyde-2,4-dichlorophenylhydrazone was obtained by filtering from the reaction mixture and removing the aqueous layer. The obtained formaldehyde-2,4-dichlorophenylhydrazone crude product was 400 g (purity 95%).

  Next, a crude product of formaldehyde-2,4-dichlorophenylhydrazone obtained in a reaction vessel equipped with a stirrer, thermometer, and Dimroth condenser was charged into a 10 L-volume four-necked flask, and 1900 g of tertiary butanol was added to the mixture. Was cooled to 10 ° C., 130.1 g of cyanic acid was added, and the mixture was stirred at the same temperature for 4 hours to obtain a mixture containing 2,4-dichlorophenyltriazolidinone.

  To the resulting mixture, 1441 g of a 10% aqueous sodium hypochlorite solution was added dropwise over 45 minutes so that the temperature of the mixture did not exceed 10 ° C. After dropping, the mixture was stirred at 10 ° C. for 1 hour, and further stirred at 25 ° C. for 3 hours to obtain a mixture containing the title target compound.

  Next, 359 g of a 48% aqueous sodium hydroxide solution was added to the obtained mixture, and the mixture was stirred at 80 ° C. for 2 hours. Then, tertiary butanol was distilled off from the mixture. After 990 g of dichloroethane was added to an aqueous mixture containing the sodium salt of the title compound and impurities and the mixture was stirred and washed to remove impurities from the aqueous layer, the mixture was allowed to stand and separated. The aqueous layer containing the sodium salt of the title target compound obtained by liquid separation was cooled to 20 ° C., and 1660 g of 18% hydrochloric acid was added dropwise over 60 minutes to neutralize the water layer and The compound was released and the precipitated crystals were collected by filtration and washed with 2000 g of water.

The obtained crystals were sufficiently dried in a vacuum dryer to obtain 468 g (yield 94%, purity 99%) of the title target compound. The melting point was 190 to 191 ° C. EI-MS: M ⁺ 229.

[Comparative manufacturing example]
1- (2,4-dichlorophenyl) -1,2,4-triazol-5-one was produced in accordance with the examples described in WO02 / 12203 (Patent Document 2).
<Production of 1- (2,4-dichlorophenyl) -1,2,4-triazol-5-one>
In a 10 L four-necked flask, 51.5 g of sodium hydroxide was dissolved in 250 g of water, and 1300 g of t-butyl alcohol was added.

Next, after adding 105 g of 37 % aqueous formaldehyde solution at 20 ° C., 250 g of 2,4-dichlorophenylhydrazine hydrochloride was added over 30 minutes, and the mixture was stirred at 20 ° C. for 2 hours.

  Next, the reaction mixture is brought to 10 ° C. in an ice-water bath, 127 g of 90% sodium cyanate suspended in 500 g of water is added at once, and 80 g of water is used to wash away sodium cyanate adhering to the container, and washing is performed. The liquid was poured into the flask. The addition of sodium cyanate increased the temperature of the reaction mixture by 15 ° C.

After the addition of sodium cyanate, the reaction mixture was cooled to 10 ° C. and then 119 g of acetic acid was added dropwise over 15 minutes.
Immediately after the addition of acetic acid, reddish brown candy-like insoluble matter began to form, and stirring became difficult due to a large amount of reddish brown candy-like insoluble matter. The mixture was further stirred for 2 hours.

Thereafter, 730 g of 12% sodium hypochlorite aqueous solution was dropped over 90 minutes while maintaining the temperature at 10 ° C.
After dropping, the mixture was stirred for 1 hour in an ice-water bath and further stirred at room temperature for 4 hours.

After completion of the reaction, the reaction mixture was concentrated by removing t-butyl alcohol under reduced pressure.
To this was added 1000 g of toluene and 320 g of 30% aqueous sodium hydroxide solution, and the mixture was vigorously stirred to extract the title target compound. After separation, the separated aqueous layer was washed with 200 g of toluene and separated, and 260 g of 35% hydrochloric acid was added dropwise over 30 minutes while cooling the aqueous layer to 15 ° C.

The precipitated solid was collected by filtration and washed with 500 g of water.
The solid was sufficiently dried to obtain 167 g (yield 62%, purity 81%) of the title compound.
In the above comparative production example, the low yield and purity of 1- (2,4-dichlorophenyl) -1,2,4-triazol-5-one obtained are mainly due to formaldehyde-2 which is unstable to acid. This is probably because a part of 1,4-dichlorophenylhydrazone was dimerized in the presence of acetic acid to form poorly soluble tetrazine.

  According to the method for producing phenyl triazolinones according to the present invention, it is possible to produce high-purity phenyl triazolinones in a simpler, safer, lower cost and higher purity by using cheaper raw materials. . Therefore, the method for producing phenyltriazolinone of the present invention is also suitable for large-scale industrial implementation.

Claims (5)

General formula (1)

(In formula (1), X represents a halogen atom or a lower alkyl group having 1 to 6 carbon atoms, n represents an integer of 0 to 5. When n represents an integer of 2 or more, a plurality of X general by after the may be the same or different.) in aniline compound is reacted with nitrous acid salt showing diazonium salt together, in which the sulfite or reduced with bisulfite, then hydrolyzing Formula (2)

(In formula (2), X and n are the same as those in formula (1).)
To form a phenylhydrazine compound ,
The obtained phenylhydrazine compound (2) and formaldehyde are reacted at pH 5-10 in the presence of a catalyst,
General formula (3)

(In formula (3), X and n are the same as those in formula (1).)
Formaldehyde-phenylhydrazone compound shown in
The formaldehyde-phenylhydrazone compound (3) is reacted with cyanic acid,
General formula (4)

(In formula (4), X and n are the same as those in formula (1).)
A phenyl triazolidinone compound shown in
This phenyltriazolidinone compound (4),
A general formula (5) characterized by reacting a hypohalite and an oxidant selected from oxygen in the absence of a catalyst or in the presence of an oxidation catalyst

(In formula (5), X and n are the same as those in formula (1).)
A method for producing a phenyltriazolinone compound shown in FIG. General formula (2)

(In formula (2), X and n are the same as those in formula (1).)
Preparation of phenyl triazolopyrimidines compound of Claim 1 which comprises using a crude product of phenyl hydrazine compound obtained by removing the aqueous layer from the reaction mixture containing phenyl hydrazine compounds shown. General formula (3)

(In formula (3), X and n are the same as those in formula (1).)
Preparation of phenyl triazolopyrimidines compound of Claim 1 which comprises using a crude product of phenyl hydrazone compounds - formaldehyde obtained by removing the aqueous layer from the reaction mixture containing phenylhydrazone compound - formaldehyde shown in Law. General formula (1)

(In formula (1), X represents a halogen atom or a lower alkyl group having 1 to 6 carbon atoms, n represents an integer of 0 to 5. When n represents an integer of 2 or more, a plurality of X or different are identical to one another.) in aniline compound shown by the reaction in the presence of an organic solvent and nitrite salt according to claims 1, characterized in that the diazonium salt to claim 3 A process for producing a phenyltriazolinone compound . General formula (4)

(In the formula (4), X, n are the same. As in the formula (1)) and phenyl thoria oxazolidinone compounds shown, and an oxidizing agent selected from among the hypohalite and oxygen, By reacting in the absence of a catalyst or in the presence of an oxidation catalyst and then treating with alkali,
General formula (5)

(In formula (5), X and n are the same as those in formula (1).)
Preparation of phenyl triazolopyrimidines compound according to any one of claims 1 to claim 4, wherein purifying the phenyl triazolopyrimidines compounds shown.