JP3117580B2 - Method for producing 3- (phenylsulfonyl) -1,2,4-triazoles - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a 3- (phenylsulfonyl)-such as 3- (2,4,6-trimethylphenylsulfonyl) -1,2,4, -triazole useful as an intermediate for herbicides. The present invention relates to an industrial method for producing 1,2,4-triazoles.

[0002]

2. Description of the Related Art It is generally known that a sulfide compound is oxidized by hydrogen peroxide to be converted into a sulfone compound. When the sulfide compound is water-soluble, it can be reacted with hydrogen peroxide in the form of an aqueous solution.
When the sulfide compound is insoluble in water, acetic acid is often used as a reaction solvent. Generally, in these reaction systems, a sulfone compound is obtained in high yield.

[0003]

However, the object of the present invention, 3- (phenylsulfonyl) -1,2,2,
In the case of 4-triazoles, depending on the quality of the starting material 3- (phenylthio) -1,2,4-triazoles, the reaction may not proceed well, resulting in low yield and low quality. The present invention relates to 3- (phenylthio) -1,2,4-
An object of the present invention is to provide a method for industrially producing high-quality 3- (phenylsulfonyl) -1,2,4-triazoles from triazoles in high yield.

[0004]

The inventor of the present invention reacted 3- (phenylthio) -1,2,4-triazoles with hydrogen peroxide in acetic acid to give 3- (phenylsulfonyl).
In the production of -1,2,4-triazoles, the content of heavy metal mixed in the starting material, 3- (phenylthio) -1,2,4-triazole, is extremely low with respect to the reaction yield. Was found to be an important factor. That is, 3- (phenylthio)-containing a heavy metal of a certain content or more.
In the case of 1,2,4-triazoles, the 3- (phenylsulfonyl) -1,2,4-triazole produced is low-yield and low-purity simply by reacting in a conventionally known manner. It has been found that only in the case of a raw material containing less heavy metal than a certain specific content, an industrially satisfactory yield and product purity can be obtained, and the present invention has been completed by applying this.

[0005] Further, even in the case of a raw material having a high content of heavy metals, when a reaction is carried out using a specific reaction catalyst, a yield and a product purity equivalent to or higher than those of a raw material containing less heavy metal can be obtained. Having found this, the present invention has been completed.

That is, the present invention provides the following general formula:

Embedded image (Wherein, Χ _{1 to} Χ ₅ represent a hydrogen atom or an alkyl group having 1 to 3 carbon atoms which may be substituted with a hydroxyl group or a halogen group.)
The 1,2,4-triazoles are reacted with hydrogen peroxide in acetic acid to give the following general formula:

Embedded image (Wherein Χ _{1 to} Χ ₅ have the same meanings as described above), which is a method for producing 3- (phenylsulfonyl) -1,2,4-triazoles represented by the formula: A method characterized in that the content of heavy metals in -1,2,4-triazoles is 50 mg / kg or less.

Further, the present invention provides a compound represented by the following general formula:

Embedded image (Wherein, Χ _{1 to} Χ ₅ represent a hydrogen atom or an alkyl group having 1 to 3 carbon atoms which may be substituted with a hydroxyl group or a halogen group.)
The reaction of 1,2,4-triazoles with hydrogen peroxide in acetic acid in the presence of a reaction catalyst gives the following general formula:

Embedded image (Wherein, Χ _{1 to} Χ ₅ have the same meanings as described above.) Wherein the reaction catalyst is phosphorous An acid, condensed phosphoric acid, sulfuric acid, sulfonic acid, phosphonic acid, or a mixture of two or more of these.

The 3- (phenylthio) -1,2,4-triazole, which is a main raw material in the present invention, is represented by the above-mentioned general formula. In particular, X ₁ and X ₃
And 3- (2,4,6-trimethylphenylthio)-, wherein X ₅ is a methyl group and X ₂ and X ₄ are hydrogen atoms.
1,2,4-triazoles are the main objects. Therefore, the 3- (phenylsulfonyl) -1,2,4-triazoles produced according to the present invention are those represented by the above general formula, and in particular, X ₁ , X ₃ and X ₅ are methyl groups. Wherein X ₂ and X ₄ are hydrogen atoms;
(2,4,6-trimethylphenylsulfonyl)-
1,2,4-triazoles are the main objects.

The heavy metals referred to in the present invention are iron, chromium, nickel, copper, manganese, lead and the like. The total value of the heavy metal content in the raw material 3- (phenylthio) -1,2,4-triazole has a very important effect on the reaction, and the reaction is carried out with a raw material having a total heavy metal content exceeding 50 mg / kg. In this case, a simple reaction causes a decrease in yield and a decrease in quality, and it is impossible to achieve the object of the present invention. Therefore, the raw material 3- (phenylthio)
The total value of the heavy metal content in the -1,2,4-triazoles must be 50 mg / kg or less.
Preferably, it is in the range of 40 mg / kg.

However, even if the raw material contains more than 50 mg / kg of heavy metal, phosphoric acid, condensed phosphoric acid,
If sulfuric acid, sulfonic acid, phosphonic acid, or a mixture of two or more thereof is used as a reaction catalyst, low yield and low quality can be improved, and the object of the present invention can be achieved.

The condensed phosphoric acid includes pyrophosphoric acid, metaphosphoric acid, tripolyphosphoric acid, hexametaphosphoric acid and the like. These condensed phosphoric acids are commercially available in the form of a sodium salt other than pyrophosphoric acid. In this case, it is necessary to neutralize with an acid such as sulfuric acid and use it in the form of a free acid. Therefore, among these condensed phosphoric acids, pyrophosphoric acid is the easiest to use and is preferred.

Sulfonic acid is methanesulfonic acid,
Examples thereof include trifluoromethanesulfonic acid and a sulfonic acid-type ion exchange resin, and a water-soluble sulfonic acid such as methanesulfonic acid is particularly preferable.

As the phosphonic acid, aminotri (methylene phosphonic acid), 1-hydroxyethylidene-1,1-
It is possible to use diphosphonic acid, ethylenediaminetetra (methylenephosphonic acid), ethylenediaminepenta (methylenephosphonic acid) and the like.

These acids, which are available in a free form, can be used as they are. Those which are commercially available in the form of a sodium salt can be used after acidification with an acid such as sulfuric acid. For example, a combination of sulfuric acid and a condensed phosphate is preferred because it gives good results.

The use amount of these reaction catalysts is preferably 0.1 to 10.0% by weight based on the total amount of acetic acid and hydrogen peroxide, and particularly preferably 0.5 to 3% by weight. .
Preferably, it is used in the range of 0% by weight. 0.1% by weight
Below, the effect is small, and the use of 10% by weight or more is disadvantageous in cost.

As the hydrogen peroxide used in the present invention, for example, an aqueous solution having a concentration of 20 to 70% by weight can be used, and a hydrogen peroxide having a concentration of 30 to 60% by weight is particularly preferable. Hydrogen peroxide is the starting material 3- (phenylthio)-
2.0 to 6.0 with respect to 1,2,4-triazoles.
It is preferable to use it in the range of twice the molar amount, especially 3.5 to 3.5 times.
It is preferably used in a range of 4.5 moles.

The acetic acid used as a reaction solvent in the present invention may be not only 100% acetic acid but also glacial acetic acid or an aqueous acetic acid solution containing water at an arbitrary ratio. The reaction temperature is
The range of 60-100 degreeC is preferable, and especially 70-95 degreeC
It is preferable to carry out within the range.

In the reaction of the present invention, one sulfur atom is contained on the way from 3- (phenylthio) -1,2,4-triazole to 3- (phenylsulfonyl) -1,2,4-triazole. An oxygenated sulfoxide compound is formed as an intermediate, which is sequentially converted to a sulfone compound. Therefore, if the reaction is incomplete, a large amount of the sulfoxide compound is contained in the product, which causes a decrease in the purity of the product.

Further, after the end point of the reaction, by-products in which OH is further added to the benzene nucleus of the sulfone compound are produced. Therefore, if the reaction is driven too much, this also lowers the product purity.

[0020]

The present invention is directed to 3- (phenylthio)-
In the reaction between 1,2,4-triazoles and hydrogen peroxide, if a large amount of heavy metal is present in the raw material, it is clarified how this acts to reduce the product yield, and the mechanism thereof. is not.

However, as will be described later in Examples and Comparative Examples, the amount of oxygen gas generated by decomposition of hydrogen peroxide does not change much depending on the presence or absence of heavy metal, and the ineffective consumption of hydrogen peroxide to organic substances Is presumed to be promoted by heavy metals. It is a surprising fact that mere ineffective decomposition of hydrogen peroxide by heavy metals is not a cause of low yield. In this reaction, it is considered that heavy metals act as catalysts to promote side reactions. Therefore, in order to avoid a low yield, it is extremely important to select a raw material containing no heavy metal.

The mechanism of action of the reaction catalyst in the present invention is also unknown, but it is presumed that the reaction is promoted by protonation to sulfur atoms. Also,
Condensed phosphoric acid and phosphonic acid are considered to be more effective because they also function in blocking metal.

[0023]

As described above, according to the method of the present invention, the yield is not reduced by unintended side reactions,
The desired stable reaction can be caused, and high-quality 3- (phenylsulfonyl) -1,2,4-triazoles can be industrially produced in high yield. In addition,
In the present invention, the use of a specific acid as a reaction catalyst is mainly intended for a case where a raw material 3- (phenylthio) -1,2,4-triazole having a heavy metal content exceeding 50 mg / kg is used. , 50 mg / kg or less is more effective in improving the yield and quality and shortening the reaction time.

[0024]

The present invention will be described below in more detail with reference to Examples and Comparative Examples. Examples 1 to 19 3- (2,4,6-trimethylphenylthio) -1,
2,4-triazole (hereinafter abbreviated as TPTT)
Was used as a starting material to synthesize 3- (2,4,6-triphenylsulfonyl) -1,2,4-triazole (hereinafter abbreviated as TPST).

The following four types of TPTT were used as raw materials. (1) Heavy metal content is Fe 28, Cr 0.5, N
i 0.1, Cu 0.3, Mn 0.3, Pb 3.
9 mg / kg (total value 33.1 mg / kg),
TPTT with a purity of 82.34%. (2) The heavy metal content is Fe 73, Cr 11, Ni
8.4, Cu 0.9, Mn 1.1, Pb 0.5
TPTT with each mg / kg (total value 94.9 mg / kg) and purity 74.34%. (3) The heavy metal content is Fe 43, Cr 5.8, N
i 5.8, Cu 2.8, Mn 0.9, Pb 0.
9 mg / kg (total value 59.2 mg / kg),
TPTT having a purity of 84.73%. (4) The heavy metal content is Fe 3.8, Cr 0.3,
Ni 0.6 mg / kg (Total value: 4.7 mg / kg)
TPTT having a purity of 83.27%.

In a 500 ml glass reactor, pure components 3
TPTT containing 7.28 g (0.17 mol) was added, 137.97 g of acetic acid, 12.41 g of water and a predetermined amount of the reaction catalyst shown in Table 1 were added, and the mixture was heated to 70 ° C. 35% by weight of H
41.73 g of ₂ O _{2 was} added dropwise to the reactor while maintaining the temperature at 70 ° C. If 20 minutes have passed since the dropping, the temperature was raised to 95 ° C.
, And 41.71 g of 35% by weight H ₂ O _{2 were} added dropwise over 1 hour. The reaction solution was analyzed by HPLC (High Performance Liquid Chromatography) every time, and the time point at which the yield of TPST became maximum was determined as the end point of the reaction. The first stage H ₂
The start of the reaction is defined as the start of O ₂ addition. After completion of the reaction, 186.10 g of pure water was added and the mixture was cooled, and the crystals were separated by filtration, washed with water and dried to obtain TPST. The obtained T
The melting point of PST was 229-230 ° C (after recrystallization with ethanol). The product was analyzed by HPLC, yield and purity were calculated, and the results are shown in Table 1. Incidentally, the amount of oxygen gas coming generated during the reaction was measured by receiving the syringe barrel, H ₂
The decomposition rate of O ₂ was also calculated. In Table 1, ATMPA: aminotri (methylene phosphonic acid) HEDHA: 1-hydroxyethylidene-1,1
-Diphosphonic acid EDTMHA: Ethylenediaminetetra (methylenephosphonic acid) EDPMHA: Ethylenediaminepenta (methylenephosphonic acid)

Comparative Examples 1 and 2 TPST was obtained in the same manner as in the above Examples except that the reaction was carried out without using a reaction catalyst. Table 1 shows the obtained results.

[0028]

[Table 1]

──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Hiroshi Sugiyama Chugai Pharmaceutical Co., Ltd. 3-41-8 Takada, Toshima-ku, Tokyo (72) Inventor Masaki Takeuchi 3-41-8 Takada, Toshima-ku, Tokyo Chugai Pharmaceutical Co., Ltd. (56) References JP-A-3-279368 (JP, A) (58) Fields investigated (Int. Cl. ⁷ , DB name) C07D 249/12 CA (STN) REGISTRY (STN)

Claims (3)

(57) [Claims] 1. The following general formula: (Wherein, Χ _{1 to} Χ ₅ represent a hydrogen atom or an alkyl group having 1 to 3 carbon atoms which may be substituted with a hydroxyl group or a halogen group.)
The 1,2,4-triazoles are reacted with hydrogen peroxide in acetic acid to give the following general formula: (Wherein, Χ _{1 to} Χ ₅ have the same meanings as described above.) A method for producing 3- (phenylsulfonyl) -1,2,4-triazoles represented by the formula: -The above method, wherein the content of heavy metal in the 1,2,4-triazole is 50 mg / kg or less. 2. The following general formula: (Wherein, Χ _{1 to} Χ ₅ represent a hydrogen atom or an alkyl group having 1 to 3 carbon atoms which may be substituted with a hydroxyl group or a halogen group.)
The 1,2,4-triazoles are reacted with hydrogen peroxide in acetic acid in the presence of a reaction catalyst to give the following general formula: (Wherein, Χ _{1 to} Χ ₅ represent the same meaning as described above.) A method for producing 3- (phenylsulfonyl) -1,2,4-triazoles represented by the formula: The above method, which is an acid, condensed phosphoric acid, sulfuric acid, sulfonic acid, phosphonic acid, or a mixture of two or more thereof. 3. The method according to claim 2, wherein the amount of the reaction catalyst used ranges from 0.1 to 10.0% by weight of the total amount of acetic acid and hydrogen peroxide.