JP3186378B2 - 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 1H-1, such as tazobactam,
It is useful as a raw material for β-lactam antibiotics containing 2,3-triazole.

[0002]

2. Description of the Related Art The applicant of the present invention synthesizes and separates N-acyl-1,2,3-triazole from Japanese Patent Application No. 05-101236, and hydrolyzes it with an aqueous alkali solution to obtain 1H.
It was proposed as a method for obtaining -1,2,3-triazole. However, this method comprises (1) N-acyl-1,2,2,
It is necessary to separate 3-triazole, and (2) water needs to be added for hydrolysis.
Since 2,3-triazole has a high solubility in water,
(3) N-acyl-1,
The 2,3-triazole compound was unsatisfactory in that it had poor thermal stability and required careful handling.

[0003]

DISCLOSURE OF THE INVENTION The present invention provides an efficient and stable method of separating 1H-1,1 without separating a heat-labile N-acyl-1,2,3-triazole compound.
It is intended to provide an industrial process for 2,3-triazole.

[0004]

The present invention provides a compound represented by the general formula (I):

[0005]

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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), wherein glyoxal monooxime acylhydrazone and acetic anhydride are used in the presence of a base. Under the reaction, the N-acyl-
A first step of obtaining a 1,2,3-triazole solution, and in this solution an N-acyl-1,2,3-triazole,
General formula (II)

[0007]

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(Wherein R ¹ represents an alkyl group having 1 to 6 carbon atoms) to obtain 1H-1,2,3-triazole by reacting it with a lower aliphatic alcohol represented by the following formula: The present invention relates to a method for producing 1H-1,2,3-triazole comprising the steps of:

The present invention provides, for example, the following reaction formula (I)
The first reaction which can be represented by (triazole conversion step)
And a second reaction (alco-lysis step) that can be represented by the reaction formula (II). Reaction formula (I)

[0010]

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Reaction formula (II)

[0012]

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First Step (Triazolation Step) In the glyoxal monooxime acylhydrazone (compound I) represented by the general formula (I) used in this step, R is a hydrogen atom, an alkyl having 1 to 4 carbon atoms. Represents a phenyl group or a phenyl group which may be substituted. R
Examples of the alkyl group represented by are linear or branched alkyl groups having 1 to 4 carbon atoms, preferably a methyl group and an ethyl group, and more preferably a methyl group. The optionally substituted phenyl group represented by R includes, for example, a phenyl group substituted with a halogen atom, and is preferably a p-fluorophenyl group, a p-chlorophenyl group, or a p-bromophenyl group, More preferably, it is a p-chlorophenyl group.

Specific examples of the base used in the triazolation step of the present invention include sodium or potassium salts of organic carboxylic acids such as sodium acetate, and inorganic weak salts such as sodium carbonate, sodium hydrogen carbonate and potassium carbonate. Basic salts can be mentioned, and preferred are sodium acetate, sodium carbonate and potassium carbonate. The amount of the base to be used is generally 0.05 to 1 mol of compound I.
2.0 mol, preferably 0.1 to 1.2 mol.

In this step, a solvent may or may not be used, but the solvent used is not particularly limited as long as it does not participate in the reaction. Examples of the solvent to be used include aromatic hydrocarbon solvents such as benzene and toluene, and ester solvents such as methyl acetate and ethyl acetate. Ethyl acetate and toluene are preferred, and toluene is particularly preferred. The amount of the solvent to be used is not particularly limited, but is usually 1 to 20 ml per 1 g of compound Ig.

The amount of acetic anhydride used in this step is usually 1.0 to 10 mol, preferably 1.0 to 3.0 mol, per 1 mol of compound I.

The reaction temperature in this step is generally 70
To 100 ° C, preferably 85 to 100 ° C.
If the reaction temperature is too high, the resulting N-acyl-1,
It decreases because 2,3-triazole is decomposed.

The reaction time in this step is usually 1 to 5 hours, preferably 2 to 4 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.

In this step, when a solvent is used,
The reaction product mixture is obtained in a suspended state, but may be subjected to the second step (alco-lysis step) described below as it is, or may be subjected to the second step after filtering insolubles.

Second step (alcolysis step) The lower aliphatic alcohol represented by the general formula (II) (compound I) used in the alcoholysis step in the present invention
Examples of R ^{1 in} I) include a straight-chain or branched alkyl group having 1 to 6 carbon atoms, preferably a methyl group, an ethyl group, or a propyl group (including each isomer);
More preferred are a methyl group and an ethyl group.

The amount of compound II used is the same as the amount of triazo-
The amount is specified by the amount (mol) of acetic anhydride used in the oxidation step, and is usually 1 to 10 mol, preferably 1 to 8 mol, and more preferably 1 to 1 mol of acetic anhydride.
５5 mol.

The reaction temperature in this step is usually from -20 to
It is 50 degreeC, Preferably it is 0-40 degreeC. Since this step is an exothermic reaction, it is preferable to advance the reaction by adding Compound II dropwise while controlling the reaction temperature.

The reaction time of this step is usually 1 to 8 hours, preferably 2 to 6 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.

1H-1, produced by the reaction in this step,
2,3-Triazole can be isolated by separating the solution after filtration when there is an insoluble substance, or by isolating the solution as it is when there is no insoluble substance, for example, by concentration and distillation.

[0025]

According to the present invention, glyoxal monooxime acyl hydrazone and acetic anhydride are reacted in the presence of a base to form N-acyl-1,2.
By reacting 2,3-triazole with a lower fatty acid alcohol without separation, 1H-1,2,3-
Triazole can be obtained efficiently and stably.

[0026]

Examples are shown below. The yield in the examples is the yield of 1H-1,2,3-triazole (mol) based on glyoxal monooxime acylhydrazone (mol).

Example 1 Glyoxal monooxime acetylhydrazone 588
g (4.46 mol) and 74.8 g of sodium acetate
(0.91 mol) was dissolved and stirred in 2.4 liters of toluene to obtain a mixed solution. Acetic anhydride 93 was added to the obtained mixture.
After adding 0.2 g (9.12 mol), 90-93 ° C
For 4 hours to obtain a reaction solution I. After the obtained reaction solution I was cooled to room temperature, insolubles were filtered to obtain a filtrate. After cooling the obtained filtrate to 5 ° C., 730 g of methanol was obtained.
(22.8 mol) was added dropwise so that the reaction temperature in the filtrate did not exceed 40 ° C. After completion of the dropwise addition, the mixture was further stirred for 4 hours to obtain a reaction liquid II. The resulting reaction solution II was concentrated under reduced pressure, and then subjected to distillation to give 1H-1,2,3-triazole 2
52 g were obtained (yield: 80%). The resulting 1H-1,
Each analytical value of 2,3-triazole [ ¹ H-NMR (40
0 MHz), IR, MS] were the same as those on the market.

Example 2 The same operation as in Example 1 was carried out except that the reaction scale was reduced to 1/10 of that of Example 1 and sodium carbonate was used instead of sodium acetate. -Triazole 2
5 g was obtained (yield: 80%).

──────────────────────────────────────────────────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 compound 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), and glyoxal monooxime acylhydrazone and acetic anhydride,
The reaction is carried out in the presence of a base to give N-acyl-1,2,3-
First step of obtaining a triazole solution, and N
-Acyl-1,2,3-triazole and a compound of the general formula (I
I) (Wherein, R ¹ represents an alkyl group having 1 to 6 carbon atoms), and 1H-1,
1H- comprising a second step of obtaining 2,3-triazole
A method for producing 1,2,3-triazole.