KR102425274B1 - Synthetic method of 5-(C1~C4 alkyl) tetrazole - Google Patents

Abstract

The present invention reacts a C1-C4 alkyl nitrile and an azide compound in the presence of a compound containing at least one selected from the group consisting of a Zn(II) complex as a catalyst and a carboxyl group, a hydroxyl group, a thiol group and an amino group as a zinc chelating agent It relates to a method for synthesizing 5-(C1-C4 alkyl) tetrazole, characterized in that According to the above method, expensive manufacturing equipment such as a high-pressure reactor is unnecessary, the reaction time is shortened, and the manufacturing cost can be greatly reduced due to the excellent yield.

Description

Synthetic method of 5-(C1-C4 alkyl) tetrazole

The present invention relates to a method for synthesizing 5-(C1-C4 alkyl) tetrazole.

5-(C1-C4 alkyl) tetrazole is widely used as a corrosion inhibitor in the manufacturing process of semiconductor devices and display devices.

Conventionally known methods for synthesizing 5-(C1-C4 alkyl) tetrazole, such as 5-methyl-1H-tetrazole, include methods according to Synthesis Example I and Synthesis Example II below.

[ Synthesis example I]

[ Synthesis example II]

In addition, when a Lewis acid catalyst is used, a synthesis method by an aqueous phase reaction using ZnCl ₂ and a synthesis method by an aqueous phase reaction using Co(OAc) ₂ are mentioned.

However, since the above methods are manufactured using a high-pressure reactor, expensive manufacturing equipment is required, and since the synthesis proceeds at a high temperature, the yield is decreased due to side reactions, and the reaction rate is slow.

CN103351353A

The present invention has been devised to solve the problems of the prior art,

An object of the present invention is to provide a method for synthesizing 5-(C1-C4 alkyl) tetrazole that does not require expensive manufacturing equipment such as a high-pressure reactor, shortens the reaction time, and greatly reduces the manufacturing cost due to excellent yield.

the present invention

A C1-C4 alkyl nitrile and an azide compound are reacted in the presence of a compound containing at least one selected from the group consisting of a Zn(II) complex as a catalyst and a carboxyl group, a hydroxyl group, a thiol group and an amino group as a zinc chelating agent. It provides a method for synthesizing 5-(C1-C4 alkyl) tetrazole.

According to the method for synthesizing 5-(C1-C4 alkyl) tetrazole of the present invention, expensive manufacturing equipment such as a high-pressure reactor is unnecessary, the reaction time is shortened, and the manufacturing cost of alkyltetrazole can be greatly reduced due to excellent yield. have.

The present invention reacts a C1-C4 alkyl nitrile and an azide compound in the presence of a compound containing at least one selected from the group consisting of a Zn(II) complex as a catalyst and a carboxyl group, a hydroxyl group, a thiol group and an amino group as a zinc chelating agent It relates to a method for synthesizing 5-(C1-C4 alkyl) tetrazole, characterized in that

As the Zn(II) complex, at least one selected from the group consisting of Zn(X) ₂ , ZnY and Zn ₃ Z ₂ may be used, wherein X is a monovalent anion, Y is a divalent anion, and Z is It may be a trivalent anion.

The monovalent, divalent or trivalent anion is not particularly limited as long as it can form a complex with Zn ^{2+ .}

Examples of the monovalent anion include halogen, C1-C10 alkylcarboxylate, nitrate, and the like, and examples of the divalent anion include sulfate and carbonate, and examples of the trivalent anion include phosphate and the like.

The synthesis method is illustrated and described as a reaction scheme as follows:

[Scheme I]

In the above formula,

R is a C1-C4 straight-chain or branched alkyl group,

M is Na or K.

Examples of the C1-C4 straight-chain or branched alkyl group include straight-chain or branched methyl, ethyl, propyl, and butyl.

In the present invention, as the Zn(II) complex, Zn(X) ₂ is preferably can be used More preferably, in Zn(X) ₂ , X is a halogen element, a C1-C10 alkyl carboxylate, and as the halogen element, Cl or Br may be preferably used, and the C1-C10 alkyl carboxylate Acetate may be preferably used.

5-(C1-C4 alkyl) tetrazole is produced by [2 ⁺ 3] cycloaddition reaction of N ₃ ^- to R-CN. To activate R-CN, a Lewis acid such as Zn ²⁺ is required . However, a Lewis acid such as Zn ²⁺ also acts as a Lewis acid ^for N ₃ ⁻ , so it forms a complex such as Zn(N ₃ ) ₂ , thereby reducing the nucleophilicity of N ₃ ⁻ and lowering the reactivity or even insolubility. It has a characteristic that it forms a complex and makes the reaction very slow.

Therefore, in the prior art, it is necessary to heat to a high temperature in order to break this complex. When heated in this way, R-CN is volatilized, so a high-pressure reactor had to be used. In addition, there is a problem in that the yield is reduced due to the decomposition of the reactant or product at a high temperature.

The present invention is characterized in that the problem caused by the complex formation as described above is solved by adding a zinc chelating agent. That is, according to the present invention, it is possible to carry out the reaction without using a high-pressure reactor by the method as described above, and it is possible to obtain the effect of speeding up the reaction and improving the yield.

In the synthesis method of the present invention, at least one selected from the group consisting of sodium azide and potassium azide may be used as the azide compound, and more preferably sodium azide may be used.

Compared to the azide compound, C1-C4 alkyl nitrile is used in 120 mol% to 200 mol%, Zn(II) complex is used in 50 mol% to 150 mol%, and the zinc chelating agent may be used in 10 mol% to 150 mol%.

In the synthesis method of the present invention, the zinc chelating agent may be selected from compounds containing at least one selected from the group consisting of a carboxyl group, a hydroxyl group, a thiol group and an amino group. That is, the zinc chelating agent is characterized in that it contains two or more functional groups capable of forming a coordination bond with Zn ²⁺ , ^and it is preferable that at least one of the two or more coordination-bonding functional groups is necessarily a carboxyl group in order to strengthen the binding force. do.

As a compound containing at least one selected from the group consisting of the carboxyl group, hydroxyl group, thiol group, and amino group, amino acids, citric acid, glycolic acid, thioglycolic acid EDTA [Ethylenediaminetetraacetic acid], and IDA (Iminodiacetic acid), etc. will be used. may be used, and these may be used alone or in combination of two or more.

As the amino acid, one or more compounds selected from glycine, alanine and proline are more preferably used, and among these, glycine may be more preferably used.

The synthesis method of the present invention may be carried out in water, an organic solvent, or a mixture thereof, and the solvent may be used in an amount of 100 to 1,000 parts by weight based on 100 parts by weight of the azide compound.

Examples of the organic solvent include alcohol, toluene triethylamine, and the like, and these may be used alone or in combination of two or more.

When water is used as the solvent, 5-(C1-C4 alkyl) tetrazole is obtained by extracting the produced 5-(C1-C4 alkyl) tetrazole with an organic solvent, and then concentrating the obtained organic fraction under reduced pressure. can

In addition, the synthesis method of the present invention may further increase the purity of 5-(C1-C4 alkyl) tetrazole by further performing a recrystallization process. The recrystallization may be performed by a method such as a recrystallization method according to temperature or a recrystallization method by substitution with a poorly soluble solvent.

When an organic solvent is used as the solvent, the organic solvent is removed under reduced pressure to obtain a solid mixture, and eluted using a solvent capable of selectively dissolving only 5-(C1-C4 alkyl) tetrazole. 5-(C1-C4 alkyl) tetrazole can be obtained.

Hereinafter, the present invention will be described in more detail using Examples and Comparative Examples. However, the following Examples and Comparative Examples are intended to illustrate the present invention, and the present invention is not limited by the following Examples, and may be variously modified and changed.

Example 1: 5 - methyl -1H- tetrazole synthesis

In a 250 mL round bottom flask at room temperature, 19.5 g (0.3 mole, 1.0 equiv) of NaN ₃ , 22.50 g (0.55 equiv) of ZnCl ₂ , 12.4 g (0.165 mole, 0.55 eq) of glycine, 100 mL of water, 23.5 mL (1.5 equiv) of acetonitrile ) and refluxed for 24 hours. Excess acetonitrile was removed by distillation, the reaction solution was cooled to room temperature, hydrochloric acid was added, the pH was adjusted to 2, and the mixture was stirred at room temperature for 2 hours.

The reaction solution was extracted three times with ethyl acetate, and the ethyl acetate layer was concentrated under reduced pressure to synthesize 24.92 g (93%) of 5-methyl-1H-tetrazole.

Example 2: 5 - methyl -1H- tetrazole synthesis

In a 250 mL round bottom flask at room temperature, 19.5 g (1.0 equiv) of NaN ₃ , 22.50 g (0.55 equiv) of ZnCl ₂ , 12.5 g (0.165 mole, 0.55 eq) of glycolic acid, 100 mL of water, and 23.5 mL (1.5 equiv) of acetonitrile were added. and refluxed for 24 hours. Excess acetonitrile was removed by distillation, the reaction solution was cooled to room temperature, hydrochloric acid was added, the pH was adjusted to 2, and the mixture was stirred at room temperature for 2 hours.

The reaction solution was extracted three times with ethyl acetate, and the ethyl acetate layer was concentrated under reduced pressure to synthesize 23.4 g (87.3%) of 5-methyl-1H-tetrazole.

Example 3: 5 - methyl -1H- tetrazole synthesis

In a 250 mL round bottom flask at room temperature, 19.5 g (1.0 equiv) of NaN ₃ , 22.50 g (0.55 equiv) of ZnCl ₂ , 15.2 g (0.165 mole, 0.55 eq) of thioglycolic acid, 100 mL of water, 23.5 mL (1.5 equiv) of acetonitrile was added and refluxed for 24 hours. Excess acetonitrile was removed by distillation, the reaction solution was cooled to room temperature, hydrochloric acid was added, the pH was adjusted to 2, and the mixture was stirred at room temperature for 2 hours.

The reaction solution was extracted three times with ethyl acetate, and the ethyl acetate layer was concentrated under reduced pressure to synthesize 22.9 g (85.4%) of 5-methyl-1H-tetrazole.

comparative example 1: 5 - methyl -1H- tetrazole synthesis

Add acetonitrile (1.0 equiv), NaN3 (1.43 g, 1.1 equiv), ZnCl ₂ (4.5 g, 1.0 equiv), water (40 mL), and i-PrOH (4 mL) to a 250 mL round-bottom flask at room temperature. did. The reflux reaction was carried out at 170° C. for 24 hours. After cooling to room temperature, 1 N aqueous NaOH solution (2.5 equiv) was added thereto, followed by stirring for 30 minutes. The resulting solid (zinc hydroxide) was removed by filtration. The reaction solution was extracted three times with ethyl acetate, and the resulting ethyl acetate layer was concentrated under reduced pressure to synthesize 1.37 g (75%) of 5-methyl-1H-tetrazole.

comparative example 2: 5 - methyl -1H- tetrazole synthesis

In a 250 mL round bottom flask at room temperature, 19.5 g (1.0 equiv) of NaN ₃ , 22.50 g (0.55 equiv) of ZnCl ₂ , 14.8 g (0.165 mole, 0.55 eq) of oxalic acid, 100 mL of water, and 23.5 mL (1.5 equiv) of acetonitrile were added. refluxed for an hour. Excess acetonitrile was removed by distillation, the reaction solution was cooled to room temperature, hydrochloric acid was added, the pH was adjusted to 2, and the mixture was stirred at room temperature for 2 hours.

The reaction solution was extracted three times with ethyl acetate, and the ethyl acetate layer was concentrated under reduced pressure to synthesize 18.3 g (68.3%) of 5-methyl-1H-tetrazole.

comparative example 3: 5 - methyl -1H- tetrazole synthesis

NaN ₃ 19.5 g (1.0equiv), ZnCl ₂ 22.50 g (0.55 equiv), succinic acid 19.47 g (0.165 mole, 0.55 eq)_water 100 mL, and acetonitrile 23.5 mL (1.5 equiv) were added to a 250 mL round bottom flask at room temperature. It was refluxed for 24 hours. Excess acetonitrile was removed by distillation, the reaction solution was cooled to room temperature, hydrochloric acid was added, the pH was adjusted to 2, and the mixture was stirred at room temperature for 2 hours.

The reaction solution was extracted three times with ethyl acetate, and the ethyl acetate layer was concentrated under reduced pressure to synthesize 17.1 g (63.8%) of 5-methyl-1H-tetrazole.

Claims (8)

A C1-C4 alkyl nitrile and an azide compound are reacted in the presence of a compound containing at least one selected from the group consisting of a Zn(II) complex as a catalyst and a carboxyl group, a hydroxyl group, a thiol group and an amino group as a zinc chelating agent. As a method for synthesizing 5-(C1-C4 alkyl) tetrazole,
The compound comprising at least one selected from the group consisting of a carboxyl group, a hydroxyl group, a thiol group and an amino group is at least one compound selected from amino acids, citric acid, glycolic acid, EDTA [Ethylenediaminetetraacetic acid], and IDA (Iminodiacetic acid),
The method for synthesizing 5-(C1-C4 alkyl) tetrazole, characterized in that the amino acid is glycine. The method according to claim 1,
The azide compound is a method for synthesizing 5-(C1-C4 alkyl) tetrazole, characterized in that at least one selected from the group consisting of sodium azide and potassium azide. delete delete The method according to claim 1,
As the Zn(II) complex, at least one selected from the group consisting of Zn(X) ₂ , ZnY and Zn ₃ Z ₂ is used,
wherein X is a monovalent anion, Y is a divalent anion, and Z is a trivalent anion. The method according to claim 1,
Compared to the azide compound, C1-C4 alkyl nitrile is used in 120 mol% to 200 mol%, Zn(II) complex is used in 50 mol% to 150 mol%, and the zinc chelating agent is used in 10 mol% to 150 mol% A method for synthesizing 5-(C1-C4 alkyl) tetrazole. The method according to claim 1,
In the reaction, water, an organic solvent, or a mixture thereof is used as a solvent, and 100 to 1,000 parts by weight based on 100 parts by weight of the azide compound. The method according to claim 1,
In the synthesis method, 5-(C1-C4 alkyl) tetrazole produced by the above reaction is subjected to one or more processes of extraction and recrystallization to obtain 5-(C1-C4 alkyl) tetrazole A method for synthesizing (C1-C4 alkyl) tetrazole.