KR790001338B1 - Process for manufacture of organic hydrazines - Google Patents

Abstract

Organic hydrazines were prepd. by passing one or two alkyl groups substituted from chloramine such as methyl chloramine, n-propylchloramine, isobutylchloramine, or diethylchloramine into the inactive solvent of primary or secondary amine. Thus, 2-RC6H4NHNH2 [I; R = H, Me, MeO was prepd. in 80% yield by passing gaseous ClNH2 into stirred 2-RC6 H4NH2 at 94-130≰C. The concn. of I in the liq. phase was not allowed to exceed -6%.

Description

Method for preparing organohydrazine

The figure shows an apparatus used to carry out the method of the invention.

The present invention relates to a method for producing organic hydrazines.

It is already known to produce organic hydrazines such as methylhydrazine and phenylhydrazine by reacting chloramine with primary and secondary aliphatic or cycloaliphatic amines or aniline under anhydrous conditions (Angewandte Chemie 72, (1960), p. 129). -130, German Patent No. 964,865). The aliphatic hydrazine has a good yield, but according to the above-mentioned literature, the yield of the organic hydrazine is very low (only 0.2% by weight). Because of this low yield, this manufacturing method is very uneconomical. In fact, when reacted with low concentrations of aniline, the yield of phenylhydrazine is also insufficient.

The German patent example describing the reaction of chloramine with aniline does not point to any yield of phenylhydrazine. This may possibly assume that secondary products such as phenylenediamines and chloranilines are produced in significant amounts.

It is reported in the literature that the yield of phenylhydrazine is 46% (calculated based on reacted aniline) when chloramine is reacted with aniline under anhydrous conditions. J. Org. Chem. 26 (1961), 821]. However, this is not in agreement with the calculation that 1.1 g of impure phenylhydrazine is obtained from 3.1 g of aniline consumed. The yield calculated for consumed aniline is 31% of theory and the yield calculated for chloramine (50 mmol) used is 20%. The phenylhydrazine concentration in aniline is 2.6% by weight.

In view of the industrial importance of organohydrazines, in particular phenylhydrazine, in particular, in terms of being used as starting materials in the pharmaceutical field, there are known methods for reacting chloramine with liquid primary and secondary amines under practically anhydrous conditions. It was quite necessary to give more economics, ie to improve the yield of organohydrazine without introducing more technology.

The present invention solves this problem by well stirring the liquid phase containing primary or secondary amines while adding chloramine.

In the present invention, unsubstituted chloramine or chloramine substituted with one or two alkyl groups is added to a solution in which primary or secondary amine is dissolved in an inert solvent, or vigorously shaken with anhydrous solution containing primary or secondary amine solution. Provided are methods for preparing organohydrazine.

Suitable chloramines for use in the methods of the invention are, in addition to unsubstituted chloramine ClNH ₂ , chloramines having one or two alkyl groups as substituents, for example methylchloramine, n-propyl chloramine, isobutylchloramine, diethylchloramine and these are It may be prepared according to the known method described in "Allgemeine und Praktische Chemie" 21 (1970), p. 123 124; "Chemikerzeitung / Chemische Apparatur" 92 (1968) p. 383 or US Pat. No. 2,808,439].

In these preparations, chloramines are all obtained as a mixture of ammonia or used primary or secondary raw amines, inert gases such as nitrogen, and also in the form of a mixture of fine ammonium chloride or nitrates of raw amines. The gas mixture containing chloramine is introduced into a substantially anhydrous, vigorously stirred or finely powdered liquid consisting of the primary or secondary liquid amine used or a solution in which the amine is dissolved in an inert solvent or passed through a liquid phase.

Suitable primary and secondary amines include aliphatic, cycloaliphatic, aromatic and araliphatic amines such as n-butylamine, n-hexylamine, cyclohexylamine, piperidine, piperazine, aniline, diphenylamine, o- Toluidine, o-anisidine, benzidine and the like, with aniline being preferred. The amines are in liquid form or inert solvents such as aliphatic or aromatic hydrocarbons and halohydrocarbons, for example n-hexane, petroleum ether, benzene, toluene, chlorobenzene, diethyl ether, dioxane or tetrahydrofuran. It can be used in the form of a dissolved solution. The solvent is preferably used with a high melting point amine.

The more water, the lower the yield of the desired organic hydrazine, so the water content of the liquid should not exceed 0.5% by weight. If the amine or solvent used is difficult to form in anhydrous form, a known substance such as glue or gelatin is added as a heavy metal receptor to prevent the adverse effects of water.

Due to the vigorous shaking of the liquid substance, the gaseous chloramines are surprisingly elevated to temperatures above 300 ° C, while the liquidus temperature basically should not exceed 150 ° C. The temperature chosen depends on the boiling point of the amine and the solvent in the first step. The low temperature limits of the airflow and liquid material can be determined by the fact that the reaction rate is too slow at too low a temperature. Therefore, the acceptable low temperature limit should be around room temperature.

A very important feature of the present invention is the vigorous shaking or fine powdering of the liquid material during the introduction of chloramine or chloramine gas. Violent shaking is performed by circulating and / or vaporizing by stirring and / or by pumping and / or by vigorously shaking the liquid in a vibration mixer.

In order to finely powder the liquid substance, it is preferable to introduce the chloramine-containing gas through the nozzle into the compressed portion of the vertical venturi tube flowing downward. A venturi tube is a tube with a wide open end connected to a compressed central part that forms the neck. As a result of the compression, the flow rate of the gas or liquid medium through the tube increases as the pressure decreases and is adjusted back to its initial state at the wide end. In the present invention, the chloramine-containing gas is introduced into the compressed portion of the venturi tube through the nozzle to increase the velocity of the gas when it is in contact with the liquid material, so in particular, the liquid material is violently shaken and finely powdered. In each droplet, the molecules move strongly and the organic hydrazine produced on the surface is quickly transported into the droplet.

In the preparation of phenylhydrazine by adding unsubstituted chloramine to anhydrous aniline in accordance with a preferred method of the present invention, care should be taken to ensure that the content of phenylhydrazine in the liquid substance does not exceed about 6% by weight. React to form hydrazobenzene, the latter compound further reacts to produce a secondary product (up to benzene). Similar methods should not be used when using other primary and amines. These contents are slightly different in each case, but can be easily determined by the skilled person in the usual experiment.

In the reaction of unsubstituted chloramine with aniline, the content of hydrazobenzene (N, N'-diphenylhydrazine) should be varied accordingly. The same applies to the reaction with other amines.

The reaction mixture is treated in a conventional manner without vigorously shaking or finely powdering the liquid phase material. When unsubstituted chloramine is reacted with aniline to produce phenylhydrazine, the ammonium chloride produced is mechanically separated by filtration, precipitation or centrifugation, and the filtrate is treated with an alkali metal or alkaline earth metal compound before rectification. Phenyl-hydrazine is rectified and separated from aniline and minor byproducts. The distillation residue always contains a small amount of hydrazobenzene and precipitates as crystals upon cooling. The yield of phenylhydrazine is higher than 70% of theory when calculated based on the reacted aniline. The same or higher yields can be obtained using aniline having one substituent in the nucleus and having a dipole autonomy of about 1.4 to 1.9 debyes. Of course, there are also starting materials with lower yields as in all cases, but in some cases the same starting materials are known to have a significantly higher yield when reacted with chloramine by known methods, i.e. without vigorously shaking or finely powdering the liquid materials. You get The reaction according to the present invention is preferably carried out discontinuously, but good results can be obtained by continuous methods such as countercurrent method of gaseous and liquid materials.

The cause of increased yield by violently shaking or finely powdering liquid during the introduction of chloramine is tested in the reaction of unsubstituted chloramine with aniline to obtain phenylhydrazine. Chloramine reacted more quickly with the resulting phenylhydrazine than with aniline, so it was found that if phenylhydrazine remained in its site for a long time after reaction with chloramine, it reacted further to produce hydrazobenzene and other products to reduce yields. In the present invention, the generated phenylhydrazine should be removed as soon as possible from the part where chloramine comes into contact with the liquid substance to avoid such unnecessary reactions. The secondary reaction of phenylhydrazine with chloramine can be reduced by bringing chloramine into contact with finely powdered liquid substances to enhance molecular motion in the droplets as well as by widening the liquid surface. Because widening the surface reduces the surface distribution of hydrazine, increasing the likelihood that chloramine molecules will contact amine molecules, not hydrazine molecules, to produce hydrazine and the hydrazine will not react. Since phenylhydrazine is rapidly removed and finely powdered to increase the surface area of the liquid substance, phenylhydrazine can accumulate in a higher yield in the liquid substance. In terms of economy, the method of the present invention is: The Fischer method (the method of reducing diazotized aniline to sulfite) can be far superior to or at least compete with conventional methods for producing phenylhydrazine.

Organic hydrazines prepared according to the process of the present invention are important intermediates in many synthetic methods, especially in the preparation of pharmaceutical products. First, phenylhydrazine is an important starting material for the reaction for producing pyrazolone, for example by reaction with aceto acetic acid ester, in which there is no need to separate phenylhydrazine from the aniline solution.

Appropriate apparatus for carrying out the method of the present invention can be described by way of example through the drawings. The apparatus consists of three essential elements: the chloramine generator 1, the cooling section 2 and the amine reactor 3. Chloramine generator 1 is composed of a reaction cell 4 made of nickel, a nozzle 4a made of nickel, and a conduit 5 through which chlorine gas can be introduced into the reaction cell. Inlet 6 is used to introduce ammonia or amines and, together with chlorine, ammonia and / or amines, may introduce an inert gas such as nitrogen. The reaction cell 4 and the chlorine nozzle 4a are heated by the oil feed circulation heater 7 to pass hot oil through the jacket of the reaction cell and the chlorine nozzle. When chlorine reacts with ammonia, the heating temperature is about 320 ° C. The chloramine generator 1 is connected directly to the cooling section 2, which consists of a cylindrical vessel 8 with a device 9 for introducing a cooling medium through the inlet 10 and a funnel bottom 11. The cooling medium supplied through inlet 10 is diverted on guide ring 12 and flows in the direction of airflow exiting the chloramine generator. The cylindrical container 8 is preferably surrounded by an insulating jacket 13 made of a known insulating material. The funnel-shaped outlet 11 of the cooling section 2 is submerged under the surface of the liquid material in the amine vessel 3. Pump 4 ejects the liquid at right angles to the point where it is introduced and tip 15 directs the liquid to the air stream generated. The generator airflow is further reversed on the drop column 16 by the downward liquid of the pump 15. The generator gas is discharged from dropping column 16 through outlet 17.

The following examples further illustrate the invention.

Example 1

The apparatus as described above is used to carry out the method of the invention.

Chloramine generator heated to 320 ℃ by oil circulation heater 7 was charged with 220Nℓ of chlorine gas per hour (N is measured at normal pressure and normal temperature) through inlet 5 of chlorine nozzle 4a and 1.5Nm ³ per hour through inlet 6 Fill NH ₃ . Nitrogen is used as the cooling medium to introduce cooling unit 2 through inlet 10 in an amount of 12 Nm ³ per hour. A narrow annular gap between the baffle 12 and the heat-insulated bottom of the reaction cell 3, with a cylindrical nozzle inserted into the baffle ring 12, where the nitrogen stream was first upwards and later downwards. It flows uniformly coaxially into the cylindrical container 8 of the cooling part 2 through. The nitrogen stream surrounds the stream containing hot chloramine generated from the reaction cell 3. The two equilibrium streams are mixed with each other, the temperature of the air stream containing chloramine is lowered and the ammonium chloride is separated into a very finely divided form. The nitrogen stream near the wall was too fierce and the diameter of the cylindrical vessel 8 was so large (150 mm) that no hot portion could contact the interior of the vessel 8. In this way ammonium chloride does not accumulate in the inner wall of the vessel 8 and in the funnel bottom 11. The air stream containing chloramine and ammonium chloride is mixed with the cooled gas and passed directly through the aniline liquid through outlet 11 of the cooling section. Two rotary pumps 14 and 15, each having a capacity of about 6 m ³ per hour and having a gas-containing effect, violently shake aniline with a total amount of 17.14 kg and containing 0.095% by weight of water. The generator gas exiting exit 17 of dropping column 16 is substantially free of ammonium chloride and chloramine.

The reaction conditions are shown in the following table.

[table]

In the table above

α represents the molar ratio of chloramine to chlorine used, and is measured by the iodine titration method of gas collected at the end of cooling vessel 8.

β represents the molar ratio of phenylhydrazine (measured as in α above).

γ represents the molar ratio of phenylhydrazine to aniline consumed.

In addition to phenylhydrazine, small amounts of benzene, nitrogen and hydrazinebenzene are produced from aniline, not chlorinated organic compounds.

In the preparation of chloramines ammonium chloride and nitrogen are produced.

The fact that β is smaller than γ indicates that some of the chloramine breaks down into ammonium chloride and nitrogen in liquid aniline. The reaction mixture is treated by filtering off the dispersed ammonium chloride and mixing the filtrate with 100 g of 30% NaOH. The dissolved NH ₃ is blown off under a nitrogen atmosphere of 100 mmHg, the azeotrope of benzene and water-aniline is distilled first, followed by distillation of aniline at a temperature of 160 ° C., and the pressure is further reduced to distill phenylhydrazine.

The amount of pure phenylhydrazine produced amounts to 95% as determined by iotitration. Pure hydrazo benzene can be obtained by crystallization from the distillation residue.

After partial condensation, the generated gas is recycled and nitrogen and benzene are discarded. In the following table, the important figures of the invention when tested according to example 1 are compared with those of the corresponding literature.

Example 2

The reaction is carried out with the apparatus described above.

Instead of aniline, 17.21 kg of 0-toltuidine is used and tested under the following conditions.

375 Nℓ of Cl ₂ per hour

2.6 Nm ³ per hour NH ₃

10 Nm ³ , cooled N ₂ per hour

Temperature of oil flowing into the heating jacket of the reaction cell: 327 ℃

Temperature of oil flowing out of the heating jacket of chlorine nozzle 4: 307 ℃

Temperature of 0-toluidine 40 ℃

About 70 minutes

O-tolylhydrazine is obtained in the form of a 5.0% solution. The molar ratio of O-tolylhydrazine to chloramine (β) used when titrating O-tolylhydrazine by iodine titration was 0.75 and the molar ratio of O-tolylhydrazine to toluidine (γ) consumed was 0.85% (by iodo titration method). proper). Both results are better than when phenylhydrazine is prepared according to Example 1 and the content of O-tolylhydrazine in the reaction solution increases more drastically.

Since O-tolylhydrazine is rectified and separated in the same manner as in Example 1 phenylhydrazine, a considerable loss is caused by decomposition. Thus, a solution of O-tolylhydrazine in O-toluidine is filtered to separate ammonium chloride, and methanol and water are separated. After addition, the solution is directly reacted with a stoichiometric acetoacetic acid methyl ester at 85 ° C. for 2 hours to yield 1-0-tolyl-3-methyl-pyrazol-5-one in 88% of theory. It is surprising that the reaction yields high yields of pyrazolone derivatives in the expectation that excess 0-toluidine will react simultaneously with the acetoacetic acid ester.

Example 3

The apparatus of Example 1 is fed 21.8 kg of freshly distilled 0-anisidine with a water content of 0.12% by weight. Other reaction conditions are as follows.

375 Nl Cl per hour

2.63Nm ³ of NH ₂ per hour

N ₂ at 10 Nm ³ per hour (used as cooling medium)

Temperature of heating circulation oil: about 325 ℃

Reaction time: about 70 minutes

After chloramine was introduced into 0-anisidine for 70 minutes, the 0-anisidine contained 4.3% by weight of 0-methoxyphenylhydrazine.

The average is

α 0.86

β 0.49

γ 0.80 to 0.85

Since 0-methoxyphenylhydrazine is unstable at high temperatures and difficult to distill without decomposition, it is also necessary to prepare the corresponding pyrazolone by directly reacting acetoacetic acid ester with a solution dissolved in 0-anisidine.

Claims (1)

In a method for preparing an organohydrazine by introducing chloramine optionally substituted with one or two alkyl groups into a solution of a primary or secondary liquid amine, a substantially anhydrous liquid, or a primary or secondary amine in an inert solvent, A method for producing an organic hydrazine, characterized by vigorous shaking or fine powdering of a liquid phase during introduction.

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