JP3186416B2 - Method for producing 1H-1,2,3-triazole - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a novel process for producing 1H-1,2,3-triazole. 1H-1,2,
3-Triazole is useful as a starting compound for antifungal agents and agricultural germicides containing 1H-1,2,3-triazole as a partial structure. Methods of using such antifungal agents and agricultural germicides as raw materials include, for example, 1H-1,
A method for synthesizing a 2-substituted oxetane derivative using 2,3-triazole is described in JP-A-5-170763, pp. 23-24.

[0002]

2. Description of the Related Art The applicant of the present invention uses glyoxal to obtain 1
As a method for producing H-1,2,3-triazole,
Japanese Patent Application No. 5-268840 discloses that glyoxal aqueous solution is reacted in a reaction solution of hydroxylamine salt with hydrazine monohydrate to produce glyoxal monooxime hydrazone. -2
Japanese Patent No. 38779 proposes a method for obtaining 1H-1,2,3-triazole by performing a cyclization reaction using the above glyoxal monooxime hydrazone and a condensing agent such as phosphorus pentachloride.

This method requires the synthesis of glyoxal monooxime hydrazone and a condensing agent in the cyclization reaction, so that 1H-1,2,3-
Since two steps are required to obtain triazole, the production method was not always satisfactory industrially.

[0004]

SUMMARY OF THE INVENTION According to the present invention, a sulfonylhydrazine compound is added to a mixed solution containing glyoxal and ammonia to cause a reaction, and 1H-
It is an object of the present invention to provide an industrial production method for obtaining 1,2,3-triazole.

[0005]

SUMMARY OF THE INVENTION The present invention provides a glyoxa
In a mixed solution containing toluene and ammonia

[0006]

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(Wherein R represents an alkyl group having 1 to 4 carbon atoms or a phenyl group which may have a substituent), and a reaction is carried out by adding 1H-1, The present invention relates to a method for producing 2,3-triazole.

The present invention provides, for example, the following reaction formula (I):
Can be represented by Reaction formula (I)

[0009]

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In the sulfonylhydrazine compound represented by formula (I) used in the present invention, R represents an alkyl group or an optionally substituted phenyl group, and the optionally substituted phenyl group includes a phenyl group, Represents a substituted phenyl group.

Examples of the alkyl group include straight-chain or branched alkyl groups having 1 to 4 carbon atoms such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl and t-butyl. Can be mentioned,

The substituted phenyl group includes, for example, o-tolyl group, m-tolyl group, p-tolyl group, 2,3
-Xylyl group, 2,4-xylyl group, o-cumenyl group,
1-2 carbon atoms such as m-cumenyl group and p-cumenyl group
A phenyl group substituted with the above alkyl group, o-chlorobenzene, m-chlorobenzene, p-chlorobenzene, o-bromobenzene, m-bromobenzene, or a halogen atom such as p-bromobenzene. Phenyl group.

R is preferably methyl, ethyl, phenyl, o-tolyl, m-tolyl, p-tolyl, p-fluorophenyl, p-chlorophenyl,
It is a p-bromophenyl group, more preferably a methyl group, a p-tolyl group, and a p-chlorophenyl group, and most preferably a p-tolyl group.

Specific examples of the sulfonylhydrazine compound include, for example, methylsulfonylhydrazine, ethylsulfonylhydrazine, propylsulfonylhydrazine, i-propylsulfonylhydrazine, butylsulfonylhydrazine, i-butylsulfonylhydrazine, t-butylsulfonylhydrazine and the like. Carbon number 1
Alkylsulfonylhydrazines substituted with up to 4 straight-chain or branched alkyl groups having 1 to 4 carbon atoms,

O-toluenesulfonylhydrazine, m-
Such as toluenesulfonylhydrazine, p-toluenesulfonylhydrazine, 2,3-xylylsulfonylhydrazine, 2,4-xylylsulfonylhydrazine, o-cumenylsulfonylhydrazine, m-cumenylsulfonylhydrazine, and p-cumenylsulfonylhydrazine. Alkyl-substituted phenylsulfonylhydrazines, o-chlorobenzenesulfonylhydrazine, m-chlorobenzenesulfonylhydrazine, p-chlorobenzenesulfonylhydrazine, o-bromobenzenesulfonylhydrazine, m-bromobenzenesulfonylhydrazine, p-bromobenzenesulfonylhydrazine, etc. Halogen-substituted phenylsulfonylhydrazines, benzenesulfonylhydrazine can be mentioned,

Preferred are alkylsulfonylhydrazines substituted with an alkyl group having 1 to 2 carbon atoms, tolyl-substituted sulfonylhydrazines, chloro-substituted phenylsulfonylhydrazines and benzenesulfonylhydrazine, more preferably benzenesulfonylhydrazine.
p-Toluenesulfonylhydrazine and p-chlorobenzenesulfonylhydrazine, and most preferably, p-toluenesulfonylhydrazine in terms of availability.

As the sulfonyl hydrazine compound, a commercially available compound may be used, but a compound other than a commercially available product may be, for example, an organic synthesis (ORGANIC SYNTH).
ESES, Vol. 40, 93-95, 1960). That is, after dissolving the corresponding sulfonyl chloride (RSO ₂ Cl) in tetrahydrofuran and cooling to 10 ° C., an aqueous solution of hydrazine is
The reaction solution is obtained by adding at a rate such that the temperature of the tetrahydrofuran solution is maintained at 10 to 15 ° C. The desired sulfonylhydrazine compound is obtained by washing the organic layer obtained by liquid separation from the obtained reaction solution twice with a saturated saline solution and then drying.

Glyoxal used in the present invention is usually a 40% aqueous solution. The amount of glyoxal to be used is generally 1 to 50 times, preferably 1 to 10 times, 1 mol of 1 mol of the sulfonylhydrazine compound.

The ammonia used in the present invention is
It can also be used as ammonia gas, liquid ammonia, aqueous ammonia solution or ammonia dissolved in an organic solvent. Ammonia dissolved in an organic solvent can be produced, for example, by a usual method of blowing ammonia gas into ice-cooled methanol. The amount of ammonia to be used is generally 2- to 200-fold molar, preferably 5- to 5-fold molar, per 1 mol of the sulfonylhydrazine compound.

In the present invention, for example, when a liquid substance such as liquid ammonia is used, it is not always necessary to add a reaction solvent, but in other cases, the reaction solvent is added. In that case, as the reaction solvent used,
There is no particular limitation as long as the reaction solvent dissolves necessary amounts of the sulfonylhydrazine compound, glyoxal, and ammonia without participating in the reaction.

As the reaction solvent, for example, water or an organic solvent can be mentioned, and the target compound of the present invention (1H-
Since 1,2,3-triazole) has high water solubility, an organic solvent is preferred in terms of a separation method after the reaction and the like. In this case, it is preferable that the organic solvent used as the reaction solvent and the organic solvent dissolving the starting compound are the same.

Examples of the organic solvent include lower alcohol solvents such as methanol, ethanol, propanol and isopropanol, methyl ether, ethyl ether, and the like.
Ether solvents such as propyl ether and the like, and aprotic polar solvents such as dimethyl sulfoxide, dimethylformamide and acetonitrile can be mentioned.Methanol, ethanol and the like are preferable in that they dissolve ammonia efficiently. It is a lower alcohol solvent such as propanol or isopropanol, more preferably methanol or ethanol in terms of low azeotropic temperature, and particularly preferably methanol. As the amount of the organic solvent used,
Although there is no particular limitation, the general sulfonyl hydrazine compound 1
It is 50-500 moles per mole, preferably 1-fold.
It is 00 to 500 times mol.

The reaction temperature in the present invention is generally -3.
It is 0-150 degreeC, Preferably it is 0-120 degreeC.
If it is lower than this range, it is difficult to control the temperature. If it is higher than this range, thermal decomposition or the like occurs, and the yield is remarkably reduced.

In the present invention, the reaction time is the reaction temperature,
Although it depends on the charged amount of the raw materials, it is usually 1 to 150 hours, preferably 1 to 60 hours. If the reaction time is too long, the yield will not improve, and if it is too short, the reaction will not proceed sufficiently.

The present invention can be usually carried out under normal pressure or under pressure, but it is preferable to carry out under pressure from the viewpoint of improving the yield. In this case, the reaction temperature is set to 7 in a closed container.
A natural pressure method by raising the temperature to 0 to 150 ° C can be used.

The present invention will be described in more detail below. For example, when liquid ammonia is used, a method in which glyoxal is dropped into liquid ammonia in a closed vessel, and then a sulfonylhydrazine compound is dropped and mixed and stirred. In this case, glyoxal may be dissolved in the above-mentioned organic solvent and dropped into liquid ammonia, and then a sulfonylhydrazine compound dissolved in the above-mentioned organic solvent may be dropped and mixed with stirring.

When an aqueous ammonia solution or an ammonia solution dissolved in an organic solvent is used, glyoxal is added dropwise to the ammonia solution, and then a sulfonylhydrazine compound is added, and the mixture is dissolved by stirring. After the reaction, the reaction may be performed under normal pressure or under pressure. In this case, a solution obtained by dissolving a glyoxal and a sulfonylhydrazine compound in the above organic solvent may be used.

According to the present invention, glyoxal is added to an ammonia solution dissolved in an organic solvent as ammonia.
% Glyoxal aqueous solution dissolved in an organic solvent is added to a glyoxal solution, and then a sulfonylhydrazine solution in which a sulfonylhydrazine compound is dissolved in an organic solvent is added as a sulfonylhydrazine compound, and the mixture is stirred and reacted. Is preferred. In this case, the reaction conditions such as the amount of the raw material added may be in accordance with the above reaction conditions.

After completion of the reaction, unreacted ammonia, organic solvent and water are distilled off, the residue is dissolved in methylene chloride or chloroform, and the undissolved substance is filtered off to obtain a filtrate. From the obtained filtrate, 1H-1,2,3-triazole can be easily obtained by concentration and distillation or separation by column chromatography.

[0030]

As described in the present invention, a sulfonylhydrazine compound is added to a mixed solution containing glyoxal and ammonia and reacted, whereby 1H-
1,2,3-Triazole can be obtained. That is, since 1H-1,2,3-triazole can be obtained in a single step by using a safe compound having a small explosive property, the present invention provides a safe and simple industrially usable 1H-1H compound. It can be said that this is a production method of -1,2,3-triazole.

[0031]

Examples are shown below. The yield in the examples is p-
1H- based on toluenesulfonide hydrazine (mole)
It is the yield of 1,2,3-triazole (mol).

Example 1 A 200 ml three-necked round bottom flask was charged with ammonia
Methanol mixed solution [ammonia: methanol = 1: 3
(Weight ratio); 590 mmol as ammonia] 40 g
Was added. A solution of 4.35 g of a 40% aqueous glyoxal solution (30 mmol as glyoxal) dissolved in 5 ml of methanol was added dropwise to the mixed solution under stirring, and the mixture was further stirred for 30 minutes. 5.58 g (30 mmol) of hydrazine was added to 20 ml of methanol.
Was added to obtain a mixed solution. The mixture was reacted with stirring at room temperature for 48 hours to obtain a reaction solution. Excess ammonia was distilled off from the obtained reaction solution, and a part of the remaining reaction solution was collected and quantified by gas chromatography-internal standard method. As a result, 1H-1,2,3-triazole was reduced to 0%. It was found that 0.65 g (yield: 31.5%) was produced.

The residue obtained by distilling off methanol from the reaction solution was used as a developing solvent in ethyl acetate: hexane = 7:
As a result of silica gel column chromatography using No.3, 0.57 g of 1H-1,2,3-triazole was obtained as a product. The result of NMR analysis of the product is shown in Journal of Chemical Society (B).
(J. Chem. Soc. (B), 516 (196)
7)) The results described and the IR analysis are based on the Journal of Chemical Society (B) (J. Chem. So).
c. (B), 307 (1969)).

Example 2 The amount of p-toluenesulfonide hydrazine added was 1.8.
The same operation as in Example 1 was carried out except that the amount was 6 g (10 mmol), and 0.28 g of 1H-1,2,3-triazole was obtained.
Was obtained (yield: 40.6%). The NMR analysis results of the product were obtained from the Journal of Chemical Society.
(B) (J. Chem. Soc. (B), 516 (19)
67)) and the IR analysis are based on the Journal of
Chemical Society (B) (J. Chem. So
c. (B), 307 (1969)).

Example 3 The reaction vessel was a sealed vessel of 200 ml and the reaction temperature was 90
1H-1,2,3-triazole 1.00, except that the reaction time was changed to 15 ° C. and the reaction time was changed to 15 hours.
g was obtained (yield: 48.3%). The NMR analysis results of the product were obtained from the Journal of Chemical Society.
(B) (J. Chem. Soc. (B), 516 (19)
67)) and the IR analysis are based on the Journal of
Chemical Society (B) (J. Chem. So
c. (B), 307 (1969)).

Example 4 The reaction vessel was a 200 ml sealed vessel and the reaction temperature was 90
C. and a reaction time of 15 hours, and the same operation as in Example 2 was carried out, except that 1H-1,2,3-triazole 0.40 was added.
g was obtained (yield: 58.3%). The NMR analysis results of the product were obtained from the Journal of Chemical Society.
(B) (J. Chem. Soc. (B), 516 (19)
67)) and the IR analysis are based on the Journal of
Chemical Society (B) (J. Chem. So
c. (B), 307 (1969)).

The preferred embodiment of the present invention is as follows.

1. The sulfonylhydrazine compound represented by the general formula (I)

[0039]

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Wherein R represents an alkyl group having 1 to 2 carbon atoms, a phenyl group, an o-tolyl group, an m-tolyl group, a p-tolyl group, a p-chlorophenyl group, or a p-bromophenyl group. The method for producing 1H-1,2,3-triazole according to claim 1, which is a sulfonylhydrazine compound represented by the formula:

2. The 1H-1,2,3-triazo- compound according to claim 1, wherein the sulfonylhydrazine compound is a sulfonylhydrazine compound represented by the general formula (I) wherein R is a phenyl group, a p-tolyl group, or a p-chlorophenyl group. Recipe.

3. The sulfonylhydrazine compound is represented by R
Is a sulfonylhydrazine compound represented by the general formula (I), wherein is a p-tolyl group.
Production method of 2,3-triazole.

4. The method for producing 1H-1,2,3-triazole according to claim 1, wherein the solution of the mixed solution is an organic solvent.

5. 2. The method for producing 1H-1,2,3-triazole according to claim 1, wherein the solution of the mixed solution is a lower alcohol.

6 The method for producing 1H-1,2,3-triazole according to claim 1, wherein the solution of the mixed solution is methanol.

7. The solution of the mixed solution is an organic solvent, and the sulfonylhydrazine compound is an alkyl group having 1 to 2 carbon atoms, phenyl group, o-tolyl group, m-tolyl group, p-tolyl group, p-chlorophenyl group. 1H-1,2,2 according to claim 1, which is a sulfonylhydrazine compound represented by the general formula (I), which is a p-bromophenyl group.
Production of 3-triazole.

8. The solution of the mixed solution is an organic solvent, and the sulfonylhydrazine compound has a structure in which R is a phenyl group, p
General formula (I) which is a -tolyl group or a p-chlorophenyl group
2. A sulfonyl hydrazine compound represented by the formula:
The method for producing 1H-1,2,3-triazole described in 1 above.

9. The solution of the mixed solution is an organic solvent, and the sulfonylhydrazine compound is a sulfonylhydrazine compound represented by the general formula (I) wherein R is a p-tolyl group. -Triazole production.

10. The solution of the mixed solution is a lower alcohol, and the sulfonylhydrazine compound is such that R is an alkyl group having 1 to 2 carbon atoms, a phenyl group, an o-tolyl group, m
-Tolyl group, p-tolyl group, p-chlorophenyl group, p
The 1H- according to claim 1, which is a sulfonylhydrazine compound represented by the general formula (I), which is a -bromophenyl group.
Production method of 1,2,3-triazole.

11. The solution of the mixed solution is a lower alcohol, and the sulfonylhydrazine compound is a sulfonylhydrazine compound represented by the general formula (I) wherein R is a phenyl group, a p-tolyl group, or a p-chlorophenyl group. The method for producing 1H-1,2,3-triazole described in 1 above.

12. The 1H-1 and 2H-1 compound according to claim 1, wherein the solution of the mixed solution is a lower alcohol, and the sulfonylhydrazine compound is a sulfonylhydrazine compound represented by the general formula (I) wherein R is a p-tolyl group. , 3-
Production of triazole.

13. The solution of the mixed solution is methanol, and the sulfonylhydrazine compound is such that R has 1 carbon atom.
~ 2 alkyl groups, phenyl groups, o-tolyl groups, m-
Tolyl group, p-tolyl group, p-chlorophenyl group, p-
The 1H- according to claim 1, which is a sulfonylhydrazine compound represented by the general formula (I), which is a bromophenyl group.
Production method of 1,2,3-triazole.

14. The solution of the mixed solution is methanol, and the sulfonylhydrazine compound is a sulfonylhydrazine compound represented by the general formula (I) wherein R is a phenyl group, a p-tolyl group, or a p-chlorophenyl group. The method for producing 1H-1,2,3-triazole described in the above.

15. The solution of the mixed solution is methanol, and the sulfonyl hydrazine compound is a sulfonyl hydrazine compound represented by the general formula (I) wherein R is a p-tolyl group. Production of 3-triazole.

──────────────────────────────────────────────────続 き Continued on the front page (58) Fields surveyed (Int. Cl. ⁷ , DB name) C07D 249/04 CA (STN) REGISTRY (STN)

Claims (1)

(57) [Claims] 1. A mixed solution containing glyoxal and ammonia in a mixed solution of the general formula (I): (Wherein, R represents an alkyl group having 1 to 4 carbon atoms or a phenyl group which may have a substituent).
Production method of 1,2,3-triazole.