KR100935893B1 - Process for production of 1,1'-dimethyl-5,5'-bitetrazole - Google Patents

Abstract

The present invention relates to a method for preparing 1,1'-dimethyl-5,5'-bitetrazole, which is a human body such as benzene and dichloromethane. And less harmful acetonitrile as a solvent instead of a solvent harmful to the environment.

Dimethylbitetrazol, acetonitrile, single reactor reaction

Description

Synthesis of 1,1'-dimethyl-5,5'-bitetrazole {PROCESS FOR PRODUCTION OF 1,1'-DIMETHYL-5,5'-BITETRAZOLE}

The present invention relates to a method for synthesizing 1,1'-dimethyl-5,5'-bitetrazole with low production cost and high yield.

The present invention relates to an improved method for synthesizing 1,1'-dimethyl-5,5'-bitetrazole (1,1'-dimethyl-5,5'-bitetrazole).

5,5'-bitetrazole derivatives can be prepared via various precursors. Examples include (1) cyclization of dicyogen and hydrogen azide, and (2) diazotization and cyclization of cyanoguanidine. There are two known methods of synthesizing 1,1'-alkyl or 1,1'-aryl derivatives as described in “Bis-tetrazoles as chemical blowing agents for foaming thermoplastic resins” (Ciba-Geigy, 1979, US Patent 4,142,029). Method and ”Tetrazoles: XL.Structure and basicity of 1,1'-disubstituted 5,5'-bitetrazole" (VA Ostrovskii, 1999, Russian Journal of Organic Chemistry, Vol. 35, No. 12, 1824-1830). There is a synthesis method.

According to U.S. Patent No. 44,142,029, phosphorus pentachloride and benzene were subjected to a chlorination reaction at 50 ° C as a solvent, and after the reaction, benzene was removed in vacuo, and the reaction intermediate was dissolved in dimethylformamide. . The reaction intermediate solution was slowly added to a reaction vessel in which a suspension of dimethylformamide and sodium azide was mixed, and further reacted at 100 ° C. for 3 hours, and the reaction was terminated with excess water to obtain a product.

This synthesis method is not preferable because a considerable amount of the intermediates are decomposed during the process of removing the solvent and the high temperature cyclization reaction, and it is difficult to remove dimethylformamide having high boiling point from the product. .

According to V. A. Ostrovskii, published in Russia in 1999, phosphorus oxychloride instead of benzene is used as a solvent to produce intermediates at high temperatures of 80 ° C. After the reaction, the mixture was cooled to room temperature and dichloromethane solution in which excess hydrogen azide was dissolved was added and reacted at 30 ° C. for 3 to 4 hours. After completion of the reaction, all solvent was removed and the remaining reaction mixture was poured into iced water to obtain a precipitated product.

However, the hydrogen azide used in the reaction is a harmful substance with very low boiling point. When inhaled into the human body, it decreases blood pressure with dizziness, speeds up the heart rate, and has an toxicity that causes severe ocular hyperemia. to be. In addition, this synthesis method also causes decomposition of the reaction intermediate due to the high temperature chlorination reaction, which causes a lot of loss in yield.

An object of the present invention is to provide a method for synthesizing 1,1'-dimethyl-5,5'-bitetrazole in high yield through a short reaction time and a low temperature reaction.

Method for synthesizing 1,1'-dimethyl-5,5'-bitetrazole (1,1'-dimethyl-5,5'-bitetrazole) according to the present invention for achieving the above object is acetonitrile A first step of forming an intermediate by reacting N, N'-dimethyloxamide with phosphorus pentachloride in a solvent containing actonitrile and sodium azide to the intermediate It comprises a second step of the cyclization reaction by adding.

At this time, the process of forming the intermediate and the process of the cyclization reaction is characterized in that made in the same reactor (one-pot) of 20 ℃ to 30 ℃ temperature.

In the present invention, the solid 1,1'-dimethyl-5,5'-bitetrazole produced through the cyclization reaction can be obtained, and even after the solid has been obtained by filtration, potassium hydroxide ( potassium hydroxide) solution may be added to neutralize the phosphate of 1,1'-dimethyl-5,5'-bitetrazole to obtain additional 1,1'-dimethyl-5,5'-bitetrazole. .

As described above, the present invention uses acetonitrile solvent at room temperature (ie, 20 ° C. to 30 ° C.) that is relatively lower than that of the conventionally known synthesis of 1,1′-dimethyl-5,5′-bitetrazole. Not only can it be produced at high speeds and in high yields, but all of the reactions can be carried out in a single reactor, reducing the time and cost of 1,1'-dimethyl-5,5'-bitetrazole. It provides a manufacturing method.

Chemical formula of 1,1'-dimethyl-5,5'-bitetrazole is the same as that of Chemical Formula 1.

In order to prepare 1,1'-dimethyl-5,5'-bitetrazole according to the present invention, N, N'-dimethyloxamide and phosphorus pentachloride are mixed by using acetonitrile as a solvent. -Chlorochlorinate dimethyloxamide.

The intermediate dimethyl oxalimidoyl chloride (N, N'-dimethyloxalimidoyl chloride) is formed by the above-described chlorination reaction, and a reaction formula is represented by Chemical Formula 2.

In the chlorination reaction, N, N'-dimethyloxamide solution was added to acetonitrile in order to cause reaction between N, N'-dimethyloxamide and phosphorus pentachloride. The stirring can proceed in the form of adding phosphorus pentachloride.

As described above, the present invention is characterized by using acetonitrile as a solvent when the reaction proceeds.

Acetonitrile can dissolve all or part of 1) N, N'-dimethyloxamide as well as phosphorus pentachloride and sodium azide used in the reactions described below. In contrast, N, N'-dimethyloxamide is not readily dissolved in benzene and phosphorus oxychloride, which are conventionally used as solvents, and thus the reaction proceeds in the form of a suspension, which delays the completion of the reaction and the yield is not high. Overcome the problem. 2) Since it corresponds to a polar solvent that does not affect the main reaction, the reaction as shown in Chemical Formulas 1 and 2 easily occurs even at room temperature. In addition, 3) can be used in the above two steps (chloride reaction and cyclization reaction) without removing or adding during the reaction, and 4) can be easily removed during washing or drying after completion of the reaction. In particular, it is mostly removed only by washing with water, even if there is acetonitrile that is not washed can be easily removed by the vacuum evaporation drying process.

It is preferable to make the said chlorination reaction react at room temperature, ie, 20 degreeC-30 degreeC. If the temperature is lower than 20 ℃, there is a problem that the reaction rate is slow, and if it is 30 ℃ or more, the intermediate dimethyl oxalimidoyl chloride is decomposed to yield problems. Therefore, it is most optimal to maintain 20 ° C to 30 ° C. In contrast, conventional methods (US Pat. No. 44,142,029 and methods of preparing V. A. Ostrovskii) yield significantly lower because the intermediate is produced or reacted at 30 ° C. or higher.

The intermediate produced by the chlorination reaction causes a cyclization reaction with sodium azide. This cyclization reaction results in the formation of 1,1'-dimethyl-5,5'-bitetrazole, where the reaction formula is shown in Formula 3.

For the cyclization reaction, a small amount of sodium azide is slowly added to the intermediate aqueous solution and then reacted with vigorous stirring. Here, when sodium azide is added, the reaction temperature is slowly added to the reaction temperature so as not to exceed 30 ° C, and then reacted at 20 ° C to 30 ° C. In the cyclization reaction, if the reaction rate is lower than 20 ° C., there is a problem that the reaction rate is slow. If the reaction rate is 30 ° C. or higher, the intermediate dimethyl oxalimidoyl is decomposed and the yield is lowered. It is preferable to proceed.

When the cyclization reaction proceeds to produce a white 1,1'-dimethyl-5,5'-bitetrazole solid, the reaction mixture is then filtered to remove the solvent to remove 1,1'-dimethyl. -5,5'-bitetrazole is further obtained. At this time, it is preferable to lower the reaction temperature so that 1,1'-dimethyl-5,5'-bitetrazole is well precipitated.

1,1'-dimethyl-5,5'-bitetrazole, which is not precipitated in the filtered filtrate, can be obtained by neutralizing with an aqueous potassium hydroxide solution to further precipitate. When the formation reaction of the 1,1'-dimethyl-5,5'-bitetrazole is completed, part of the product is ions due to phosphoric acid, a strong acid produced from phosphorus pentachloride or phosphorus oxychloride of the reaction mixture. It can be dissolved in an aqueous solution in the form. 1,1'-dimethyl-5,5'-bitetrazole dissolved in an aqueous solution in ionic form is precipitated by adding potassium hydroxide to the aqueous solution and neutralizing it. At this time, even if it is not potassium hydroxide, other substances may be used as long as they are capable of neutralizing the aqueous solution without reacting with 1,1'-dimethyl-5,5'-bitetrazole.

All of the reactions described above can be carried out in a single-pot. The acetonitrile used as the solvent in the present invention dissolves phosphorus pentachloride well at room temperature and also dissolves a small amount of sodium azide, so there is no need to use a new solvent for each reaction in the manufacturing process. This eliminates the need for solvent removal or addition of other solvents, thereby enabling a single reactor reaction.

Hereinafter, the present invention will be described in more detail with reference to Examples and Comparative Examples. However, the present invention is not limited to these Examples and Comparative Examples.

Example: Synthesis of 1,1'-dimethyl-5,5'-bitetrazole according to the present invention

5.9 g (0.05 mol) of N, N'-dimethyloxamide was placed in a 250 ml round bottom flask and 100 ml of acetonitrile was added.

Then, 21.0 g (0.10 mol) of phosphorus was added at a time while stirring the solution inside the flask using a magnetic stirrer at 24 ° C. As soon as phosphorus contaminant was added, the reaction temperature rose to about 28 ° C., and gas was released and changed to a clear solution within 5 minutes.

When turned into a clear solution with no further gas evolution, 13.0 g (0.20 mol) of well-dried fine powder sodium azide was slowly added while maintaining the reaction temperature not higher than 30 ° C., followed by vigorous stirring at 20 ° C. The reaction was carried out at -30 [deg.] C. for 80 minutes.

Thereafter, the reaction mixture was poured into 400 ml of ice water and stirred for 10 minutes.

This procedure produced a white solid. The white solid was filtered and washed twice with 50 ml of water and dried.

The weight of dried white solids was 4.0g.

The remaining filtrate was filtered, neutralized by adding 100 ml of 5N potassium hydroxide aqueous solution, and left for 10 minutes. The white solid produced at this time was collected by filtration, washed twice with 50 ml of water, and dried to obtain 2.7 g.

Through the above procedure, a total of 6.7 g (yield 80.2%) of 1,1'-dimethyl-5,5'-bitetrazole was obtained as a product.

As a result of analyzing the result by liquid chromatography, no impurities were detected and thus melting point measurement, elemental analysis, and infrared spectroscopy were performed without further purification.

The thermal analysis graph of the resultant 1,1'-dimethyl-5,5'-bitetrazole obtained by this example is shown in FIG. 1, and the infrared spectral spectrum is shown in FIG.

Referring to the figures, the melting point of the resultant according to the invention was very close to the literature value 204-205 ℃ to 207.5 ℃ infrared spectroscopy result is ^{1455 (㎝ -1), 1374 (} ㎝ -1), 1264 (㎝ - ¹ ), 121 (cm ^-1 ), 1137 (cm ^-1 ), and 995 (cm ^-1 ) showed major peaks.

And the theoretical value (%) in the elemental analysis is C 28.92, H 3.64, N 67.44, the result of this example was C. 29.03, H 3.57, N 67.28 was also very close to this value.

Comparative example  1: Synthesis method of cited patent (US Pat. No. 44,142,029)

Reaction vessel 1: 5.9 g (0.05 mol) of N, N'-dimethyloxamide is placed in a 250 ml round bottom flask and 100 ml of benzene is added. While stirring the reaction mixture well using a stirrer, 21.0 g (0.10 mol) of phosphorus was added thereto, and the temperature was gradually raised to 50 ° C. After 20 minutes, the generation of hydrochloric acid gas was stopped, and it was confirmed that N, N'-dimethyloxamide was dissolved. As soon as the generation of hydrochloric acid gas stopped, all the benzene was removed using a vacuum evaporator, cooled, and the remaining reaction mixture was dissolved in 50 ml of dimethylformamide.

[Reaction vessel 2]: Into a 250 mL round bottom flask, 8.5 g (0.13 mol) of sodium azide and 25 ml of dimethylformamide were added, and the solution prepared in Reaction Vessel 1 was slowly added over 10 minutes while stirring well. do. After the addition was completed, the reaction mixture was heated to 100 ° C. and reacted for 3 hours. After 3 hours, the reaction mixture was poured into 250 ml of water, and the resulting white solid was collected by filtration and washed twice with 50 ml of water. After vacuum drying, 1.95 g (yield 23.1%) of 1,1'-dimethyl-5,5'-bitetrazole was obtained.

Comparative example  2: Cited References (V. A. Ostovskii Synthesis method)

[Reaction vessel 1]: 19.5 g (0.30 mol) of sodium azide is added to a 1,000 ml round bottom flask and 100 ml of water is added to dissolve it. After melting, 500 ml of dichloromethane was added and the reaction solution was cooled to 10 ° C or lower. 16.0 mL (0.3 mol) of sulfuric acid was slowly added over 30 minutes while maintaining the temperature of the solution at 10 ° C or lower. When the addition of sulfuric acid is completed, the dichloromethane layer is separated from the aqueous layer, and 10 g of magnesium sulfate is added to remove water in the hydrogen azide / dichloromethane solution.

[Reaction vessel 2]: 5.9 g (0.05 mol) of N, N'-dimethyloxamide, 23 g (0.11 mol) of phosphorus pentachloride and 35 ml of phosphorus oxychloride were placed in a 250 ml round bottom flask under nitrogen stream at 80 ° C. While heating, stir until no more hydrochloric acid gas comes out. When the generation of hydrochloric acid gas was stopped, the mixture was cooled to room temperature and introduced into a 1,000 ml round bottom flask containing hydrogen azide / dichloromethane solution prepared in Reaction Vessel 1 at a time, followed by reaction at 30 ° C. for 4 hours. After 4 hours, all solvents were removed using a vacuum evaporator, and 600 ml of ice water was added thereto and left for 30 minutes. The resulting white solid was collected by filtration and washed twice with 50 ml water. After vacuum drying, 3.21 g (yield 38.0%) of 1,1'-dimethyl-5,5'-bitetrazole was obtained.

Comparison of Invention and Cited Invention

Table 1 compares the synthesis method of 1,1'-dimethyl-5,5'-bitetrazole of Example 1 according to the present invention with the synthesis method according to the cited invention of Examples 2 and 3. .

Example (Invention) Comparative Example 1 Comparative Example 2 Chloride reaction Pollutant equivalent 1.0 1.0 1.1 Reaction temperature (℃) 20-30 50 80 Response time (minutes) 5 30 ¹⁾ 20 Reaction solvent Acetonitrile benzene Phosphorus oxychloride Cyclization reaction Sodium azide equivalent 2.0 1.3 3.0 ²⁾ Reaction temperature (℃) 20-30 100 > 30 Response time (minutes) 80 180 240 Reaction solvent Acetonitrile Dimethylformamide Dichloromethane Neutralization reaction has exist none none Yield (%) 80 23 38 Rubbing Single reactor Multiple reactors Multiple reactors

1) Consider solvent removal time after chlorination

2) Sodium azide reacted with sulfuric acid to produce hydrogen azide

As shown in the table, according to the embodiment according to the present invention, the reaction is completed at 20 ~ 30 ℃ significantly lower than the reaction temperature 50 ℃ and 80 ℃ of Comparative Examples 2 and 3 in terms of the reaction temperature of the chloride reaction, The reaction time also corresponded to 30 minutes and 5 minutes corresponding to 1/6 and 1/4 of 20 minutes.

In addition, also in the cyclization reaction, in the case of the present invention, the reaction temperature is 20 to 30 ° C., but Comparative Example 2 and Comparative Example 3 are 100 ° C. and 30 ° C. or more, respectively, so that the reaction is completed at a significantly lower temperature. The reaction time of the cyclization reaction was also 80 minutes, whereas Comparative Example 2 and Comparative Example 3 corresponded to 180 minutes and 240 minutes, respectively, according to the preparation method according to the present invention, 1,1'-dimethyl-5,5 '. It can be seen that the time is significantly reduced when the bitetrazole is synthesized.

The yield of the present invention was 80%, which was much higher than that of 23% and 38% of each comparative example.

1 is a graph showing the results of thermal analysis of 1,1'-dimethyl-5,5'-bitetrazole.

2 is an infrared spectroscopy spectrum of 1,1'-dimethyl-5,5'-bitetrazole.

Claims (4)

A first step of forming an intermediate by reacting N, N'-dimethyloxamide with phosphorus pentachloride in a solvent containing acetonitrile, And a second step of cyclizing the reaction by adding sodium azide to the intermediate, The first step and the second step is a method for producing 1,1'-dimethyl-5,5'-bitetrazole that is made at a temperature of 20 ℃ to 30 ℃. delete The method of claim 1, The first step and the second step is a method for producing 1,1'-dimethyl-5,5'-bitetrazole, characterized in that made in the same reactor. The method of claim 1, After the cyclization reaction, the resulting solid material is filtered, and adding a potassium hydroxide solution to the filtrate to neutralize the phosphate of 1,1'-dimethyl-5,5'-bitetrazole. The manufacturing method of 1,1'- dimethyl- 5,5'-bitetrazole which makes it.

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