HU195790B - Process for producing 1,2,4-triazol - Google Patents

Abstract

Process for the preparation of 1,2,4-triazole by the ring closure of diformyl hydrazine prepared by the formylation of hydrazine and ammonia which comprises reacting ammonium formiate with hydrazine hydrate by feeding continuously hydrazine or hydrazine hydrate at 120-160<o>C to the aqueous solution of ammonium formiate and removing continuously the formed water ammonia from the mixture and isolating, if desired, the cold precipitated triazole from the mixture.

Description

The present invention relates to a process for the preparation of 1,2,4-triazole which is an important intermediate for the preparation of pharmaceuticals, mineral preservatives, paints and corrosion inhibitors.

There are several methods for the preparation of 1,2,4-triazole which can be divided into two large groups.

A common feature of one of the large groups of methods of preparation (although they may be completely different in nature) is the replacement of simple -NH 2, -SH, OH, -COOH groups of simple triazole derivatives with hydrogen. In this way, low yields of 1,2,4-triazole are obtained in several steps, so that the industrial implementation of these methods is not economical. :

Another group of methods is shown in Figs

synthesis of triazole from simple parent compounds, including economical, industrially feasible methods.

It has been known since the end of the last century that 1,2,4-triazole can be prepared by heating an equimolar mixture of formyl hydrazine and formamide (Pellizzari, Gaz. Chim. Ital. 24, 222/1894 /; Bér. 27, 1801/1894 /). .

It can also be prepared by reacting the 1,2,4-triazole hydrazinium salts with 2 moles of formamide (H.. H. Strain, J. Am. Chem. Soc. 49, 1995, 1927).

Ainsworth and Jones (J. Am. Chem. Soc. 77, 621 (1955)) prepared triazole by rapid distillation of a mixture of hydrazine hydrate and 2 moles of formamide. By-products are formed of diformyl hydrazine and ammonia. The above authors also found that diformylhydrazine, when heated in excess of ammonia in an autoclave at 200 ° C for 24 hours, gives milk in very drastic conditions in a yield of 7080% with 1,2,4-triazole.

Japanese authors (M. Sekiya and S. Ishikawa, Yakugaku Zasshi 78, 549/1958 / CA 52, 17244 f / 1958 /) investigated the reaction of hydrazine sulfate with 10 times the molar ratio of formamide and found that formyl followed by diformyl hydrazine which forms triazole with formamide during the evolution of carbon monoxide.

On the basis of these prior art, several patented processes have been developed (DE 28 02 491, DE 29 43 265, UP 4 267 347 and EP 0 044 438). The chemical essence of the processes described in the above patents is shown in the accompanying drawings 2/1.

Each of these methods uses formamide as a formylating agent and ammonia or a readily degradable ammonium moiety to ring-seal the diformylhydrazine formed. The procedures differ only in technical solutions.

The described DE 29 43 265 discloses process uses diformyl hydrazine starting material by the ring closure at ¹⁷⁰ to carry dimethylformamide solvent with ammonia, ammonium carbonate or ammonium bicarbonate at ^<l C above. The product is recovered from the reaction mixture by vacuum distillation.

The process described in DE 28 02 491 from hydrazine and formamide produces triazole in a one-step, step-up cascade reactor at a final temperature of 210240 ° C.

In the technical specification, the closest UP 4 267 347 and EP 0 044 438 discloses that hydrazine hydrate is added to an excess of formamide at a temperature above 160 ° C. UP 4 267 347 describes in detail the side effects that occur and provides a way to avoid them.

“Yields have improved with the above processes, but they have many disadvantages. For most of them, the formamide used must be separated by a separate operation (eg vacuum distillation): the formamide reaction mixture produces hazardous decomposition products (CO, HCN) at temperatures above 160 ° C; formamide. should be synthesized and isolated before use. The present invention relates to a process

For the preparation of 1,2,4-triazole by closure of the diformylhydrazine and ammonia ring formed by hydrazine formylation by reacting an ammonium formate prepared in situ from formic acid in the presence of water with continuous ammonia in the reaction mixture, hydrazine hydrate and hydrazine hydrate; the ammonium formate has a molar ratio of 1: 2 by continuously adding hydrazine or hydrazine hydrate to an aqueous solution of ammonium formate of 120-160, and continuously removing the water and ammonia formed so that the gaseous substances formed It was applied to a column at 100 ° C and after cooling the precipitated triazole was isolated in a known manner. The ammonia leaving the reaction mixture is used to prepare the ammonium formate required for the next batch and the mother liquor obtained after isolation of the product is returned to the next reaction.

The reaction can be outlined by the summation equations in Figure 2/2. The equilibrium is shifted by the irreversible formation of triazole. The actual equilibrium conditions of the reaction mixture are much more complex, since the ones shown here are more partial equilibrium, and the ring closure can consist of several elementary steps, of which only the last one is unidirectional.

It has been found in our studies of optimum reaction conditions that the hydrazine is continuously introduced into the melt of the ammonium formate and that excess ammonium formate is provided in the final stage of the addition. In this way, keeping the hydrazine concentration consistently low reduces the possibility of the formation of 4-aminotriazole. In view of the equilibrium of the reaction mixture, it is also important to remove the water that is formed.

The continuous addition of hydrazine is also advantageous because ammonia released in parallel with the addition can be maintained throughout the reaction mixture.

According to our method, hydrazine hydrate is continuously added to the melt optionally in an aqueous solution of ammonium formate immersed in a heating medium of 116-180 ° C, preferably 130-160 ° C for 4-20 hours, preferably 8-12 hours. A column having a head temperature of 95-100 ° C is used to ensure the continuous removal of water and ammonia, and to retain components with a higher boiling point than water.

The molar ratio of reagents theoretically required for the production of horseradish is hydrazine: ammonium formate - 1: 2, whereas the reagents are used in a molar ratio of 1: 2 to 1-2.3 to provide excess formylating agent in the final phase of hydrazine addition.

The preparation of 1,2,4-triazole according to our process gives the product a reaction. be crystalline from fly to cool. The mother liquor obtained after recovery of the product is a saturated solution of triazole containing an excess of formylating agent. The product can also be recovered from the mother liquor by vacuum distillation, but it is more convenient to add the mother liquor to the ammonium formate to be used in the next reaction and to provide excess of the formylating agent with the recycled mother liquor, respectively.

In our process, the ammonia formed from the reaction mixture can be conveniently used to produce ammonium formate by absorbing the ammonia obtained continuously from the reaction mixture in formic acid. Thus, only a portion of the ammonia needs to be replenished from external sources to produce the required ammonium formate.

In a preferred embodiment of the process, in parallel with the preparation of the product, the ammonium formate required for each subsequent reaction is prepared by passing through the reaction mixture the ammonia that has been supplied from an external source.

Any amount necessary for the preparation of ammonium formate; the passage of ammonia into the reaction mixture is advantageous primarily because it facilitates the removal of the formed water from the reaction mixture. However, an inert gas used for this purpose would also reduce the concentration of ammonia in the mixture.

Thus, our process utilizes hydrazine, formic acid and ammonia to produce 1,2,4-triazole. It is advisable to use as little water as possible in the hydrazine and formic acid used. Preferably, hydrazine hydrate containing 85-90% formic acid and 64% hydrazine is used. In our process, the technical grade 4 g of ammonia gas can be used without purity. In our process, the conversion of hydrazine to 1,2,4-triazole is nearly quantitative. The product is a white crystalline material with a purity greater than 95% and may have a slightly yellowish tint, which does not require further purification.

The process according to the invention is advantageous in several respects over the methods developed so far:

- The reaction temperatures are lower than those described previously. (Using a heating medium of 160 ° C, the temperature of the mixture, for example, rises from an initial 130 ° C to 160 ° C at the end of the reaction as the triazole content increases). Lower reaction temperatures reduce the rate at which hazardous decomposition products (carbon monoxide, hydrogen, hydrogen cyanide) are formed.

-. The use of ammonium formate as a formylating agent makes it possible to use the waste ammonia in the process.

The reaction partner of the highly flammable and explosive hydrazine hydrate is a melt of an aqueous salt. This greatly reduces the hazards of the procedure.

Crystallization of the product from the reaction mixture and recirculation of the mother liquor to the next reaction greatly reduces the preparation loss.

The above methods provide a high quality product by simpler means, using inexpensive raw materials in terms of formylating agent. The procedure is illustrated by the following example:

The apparatus for implementation consists of two reaction vessels. Reaction vessel # 1 is a 20 liter multi-necked glass pear that can be heated in an oil bath with adjustable temperature.

Mixed, thermometer, ammonia inlet, hydrazine dispenser and ball cooler are connected to the grinded neck of the glass sponge, which allows air to be drawn through the jacket. This is connected to a cold water cooled down cooler, which is connected to the vacuum tube by the collector. Reactor 2 is also equipped with a 20 liter multi-necked glass spark mixer equipped with a thermometer, an inlet of ammonia and a cooled water-cooled viscous condenser.

1st cycle

Reactor 1 was charged with 11.9 kg (220 mol) of 85% formic acid and saturated with ammonia while stirring. After saturation, the oil bath was heated to 160 ° C and the hydrazine hydrate was added at 10 M / H feed rate. 5.06 kg (100 mol) of 100% hydrazine hydrate were added at constant rate over a period of 9 hours. The temperature of the cooling head-36 associated with the reaction vessel is maintained at 95-100 ° C by suctioning the air in the jacket.

Water vapor and ammonia are removed from the reaction mixture, whereupon condensing the water vapor, the remaining ammonia gas is absorbed into reaction vessel 2 (10.82 kg, 200 mol) in 85% formic acid.

After the addition of the hydrazine hydrate for one hour, the reaction product was post-reacted under similar conditions and the reaction liquid was discarded at room temperature and allowed to cool to room temperature. The desired product is centrifuged and dried.

Product: 3900 g of 96% 1,2,4-triazole (GLC)

56.5% based on hydrazine 15

2nd cycle

The triazole-saturated mother liquor containing excess formylation reagent is returned to reaction vessel 1 and ammonium formate in reaction vessel 2 is added. Hereinafter, we will proceed exactly as in Cycle 1. 25

Product: 7000g of 96% 1,2,4-triazole (GLC)

97.40% based on hydrazine

3rd cycle 3 °

Using the mother liquor of cycle 2, proceed as above.

4th cycle

Using the mother liquor of cycle 3, proceed as above. _Q

Product: 7010g 96% 1,2,4-Triazole (GLC)

97.5% based on hydrazine

5th cycle

Using the mother liquor of Cycle 4, proceed as above.

Product: 7030 g of 96% 1,2,4-triazole (GLC)

97.8% based on hydrazine

6th cycle

Using the mother liquor of cycle 5, the procedure of>, 5 is as above.

Product: 7050g 96% 1,2,4-Triazole (GLC)

98.1% based on hydrazine

Cycle 7

Using the mother liquor of cycle 6, proceed as above.

Product: 7020 g of 96% 1,2,4-triazole (GLC) (Example 35)

97.7% based on hydrazine

8th cycle

Using the mother liquor of Cycle 7, we proceed as above.

Product: 7050 g 95% ob 1,2,4-triazole (GLC)

97.1% based on hydrazine

9th cycle

Using the mother liquor of Cycle 8, proceed as above.

Product: 7070g 94% 1,2,4-Triazole (GLC)

96.3% based on hydrazine

Cycle 10

Using the mother liquor of Cycle 9, proceed as above.

Product: 7050g 94% 1,2,4-Triazole (GLC)

96% based on hydrazine

After contaminating the mother liquor to a greater extent than allowed, the approximately 6 liter mother liquor is vacuum distilled to give 1800 g of 96% 1,2,4-triazole at 125-135 ° C at 13 mm Hg.

The total product of 10 consecutive reaction cycles as described above:

68970 g 95.5% 1,2,4-triazole (GLC)

95.4% based on hydrazine

PATENT CLAIMS

Claims (3)

1. Procedure 1, For the preparation of 2,4-triazole by closure of the diformylhydrazine and ammonia ring prepared by hydrazine formation, characterized in that the ammonium formate, which is also prepared in situ from formic acid in the presence of water by reacting the reaction mixture with hydrazine hydrate, a 1: 2 ratio by adding hydrazine or hydrazine hydrate to an aqueous solution of ammonium formate at 120-160 ° C, and continuously removing the water and ammonia formed so that the vaporous material formed is 95-100 It is applied to a column of head temperature C and, after cooling, the precipitated triazole is isolated in known manner. The process of claim 1, wherein the ammonia leaving the reaction mixture is used to produce the ammonium formate required for the next batch. 3. The process of claim 1, wherein the mother liquor obtained after isolation of the product is returned to the next reaction.