JPS6153345B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to the production of tetrafluorocyanopyridines by the so-called halogen exchange reaction, in which tetrachlorocyanopyridines are reacted with a fluorinating agent, in particular potassium fluoride, in a benzonitrile medium in the temperature range from 190°C to 400°C. This invention relates to a method for producing cyanopyridines.

Exchanging the halogen atoms with fluorine atoms by reacting an alkali fluoride etc. with an aromatic halide,
The so-called halogen exchange reaction has been known for a long time. At that time, dimethyl sulfoxide (DMSO), sulfolane (TMSO ₂ ), N
-dimethylformamide (DMF), N-methyl-
Aprotic polar solvents such as 2-pyrrolidone (NMP) and dimethylsulfone (DMSO ₂ ) are mainly used, and the halogen exchange reaction is carried out at a temperature below the boiling point of the solvent [for example, Ishikawa, Journal of the Society of Organic Synthetic Chemistry, Vol. Volume 25, page 808 (1967), M. Hudlicky,
Chemstry of Organic Fluorine Compounds,
Page 112 (1976) John Wiley & Sons Publishing, etc.]. In some cases, a phase transfer catalyst such as a crown compound is added to speed up the reaction rate. However, aromatic halides that can be halogen-exchanged by the above method are, for example, 2,6-dichlorobenzonitrile to 2, as described in Ishikawa et al., Journal of the Society of Organic Synthetic Chemistry, Vol.
As in the example of synthesizing 6-difluorobenzonitrile, it is usually limited to aromatic halides with a small number of halogen substituents, and it is often difficult to perform complete halogen exchange with polyhalides with larger halogen substituents.
Even if halogen exchange is complete, the yield is poor.
Furthermore, when aromatic halides are halogen-exchanged by the above method, electron-withdrawing groups (e.g. -CN group, -
The ortho and para positions of NO ₂ groups, etc.) can often be exchanged with halogen, but the meta position cannot be exchanged with halogen.

That is, in the above method, tetrafluoro-3-cyanopyridine, which is a polyhalide and has an electron-withdrawing nitrogen atom or a halogen substituent at the meta position of the cyano group, is used in the above method. Not suitable for producing pyridine. In fact, in the literature, tetrachloro-3-
A method for synthesizing tetrafluoro-3-cyanopyridine from cyanopyridine by halogen exchange in a solvent is not disclosed. In addition, using common solvents, polyhalide tetrachloro-4-
There has also been no report on a method for producing tetrafluoro-4-cyanopyridine by halogen exchange of cyanopyridine. Additionally, if the solvents commonly used in the above methods are heated to high temperatures or used for long periods of time to improve yields, decomposition reactions of the solvent or side reactions between the solvent and raw materials or products may occur. In the end, the yield cannot be improved. It also has the disadvantage that it is not easy to use industrially in terms of solvent recovery and reuse. In order to avoid the drawback that these solvents cannot be used at high temperatures, it is also common to conduct the reaction without a solvent at high temperatures of 200 to 500°C using an autoclave. Tetrafluoro-4 from tetrachloro-4-cyanopyridine at a temperature of 300°C using an autoclave without solvent.
- An example of halogen exchange of cyanopyridine is also given by R.
E. Banks et al., J. Chem. Soc. (C), 1967, p. 2089. However, since no solvent is used, it is difficult to control the temperature due to the exothermic reaction, and a large amount of carbide adheres to the container after the reaction is completed, making it difficult to implement industrially.

The present inventors have thought that it is difficult to synthesize tetrafluorocyanopyridines using the above-mentioned general methods, and even if they can be synthesized, there are many drawbacks that make industrial implementation impossible, and therefore, we have intensively investigated possible methods. As a result, tetrachlorocyanopyridines were heated at 190 to 400℃ under naturally occurring pressure using benzonitrile as a solvent.
The present inventors have completed the present invention by discovering that tetrafluorocyanopyridines can be easily produced in good yield by reacting with a fluorinating agent, particularly potassium fluoride, to exchange halogens in a temperature range of .

In the present invention, examples of tetrachlorocyanopyridines include particularly tetrachloro-3-cyanopyridine and tetrachloro-4-cyanopyridine, and tetrafluoro-3-cyanopyridine and tetrafluoro-4-cyanopyridine, respectively, are commercially available. is easily produced, but tetrachloro-2-
The method of the present invention is also advantageously applied as a method for producing tetrafluoro-2-cyanopyridine from cyanopyridine.

The invention will be explained in more detail below.

Benzonitrile, the solvent used in the present invention, is thermally stable and can therefore be used in the temperature range of 190 to 400°C, which is considered to be the temperature required for halogen exchange of tetrachlorocyanopyridines to tetrafluorocyanopyridines. Also, there is an advantage that there is no side reaction between the solvent and raw materials or products, which occurs with other solvents. In addition, the use of this solvent has the advantage of being able to easily control the temperature and prevent the formation of a large amount of carbide, unlike a manufacturing method without a solvent, making it possible to obtain the desired product in high yield during industrial implementation. have an advantage.

The fluorinating agent used in the halogen exchange reaction is generally an alkali fluoride such as cesium fluoride, potassium fluoride, or sodium fluoride, or an alkaline earth metal fluoride salt such as barium fluoride or calcium fluoride. There are many. In some cases, transition metal fluorides such as antimony fluoride are also used. In the present invention, any commonly used fluorinating agent can be used. Among these, particularly preferred is potassium fluoride, which is easy to handle and commercially available.

The fluorinating agent is required at least in an equivalent amount to the chloro atom to be substituted by the fluorine atom in the raw material tetrachlorocyanopyridine, and in the case of potassium fluoride, the amount is 4 times the mole per mole of the tetrachlorocyanopyridine. It is sufficient if there are more than that. Especially for tetrachlorocyanopyridines, potassium fluoride 4
A range of 8 moles is suitable.

The reaction temperature of the present invention is preferably in the range of 190 to 400°C. In particular, when producing tetrafluoro-3-cyanopyridine, the
When producing 4-cyanopyridine, 210 to 330
A temperature range of 0.degree. C. is preferred.

When the reaction is carried out at a low temperature, a compound in which chlorine is not completely replaced by fluorine is likely to be produced, and at a high temperature, a carbide is produced, and in both cases, the yield of tetrafluorocyanopyridines is reduced.

In the present invention, in order to react under naturally occurring pressure,
Approximately 2Kg/ ^cm2 to 15Kg/in the temperature range of 210℃ to 350℃
Although the pressure in ^cm2 gauge is shown, it may be further pressurized with an inert gas such as nitrogen.

The reaction time varies depending on the reaction temperature, but is approximately 2
A range of 48 hours is appropriate.

The raw material tetrachlorocyanopyridine is a solvent.
It is preferably added to the reaction system in an amount of about 5 parts to 50 parts per 100 parts by weight.

It is generally said that it is preferable to carry out the halogen exchange reaction under anhydrous conditions as much as possible in order to increase the reaction rate and avoid side reactions.

Commonly used DMSO, _TMSO2 , DMF,
Aprotic polar solvents such as NMP and _DMSO2 are highly hygroscopic and contain considerable water content. Therefore, prior to the reaction, it is necessary to add benzene, toluene, etc. to remove water by distillation as an azeotrope. In the present invention, benzonitrile does not have hygroscopic properties, so its operation is not required in principle. However, potassium fluoride used as a fluorinating agent has high hygroscopicity, so in some cases it is preferable to add benzene, toluene, etc. to remove water by distillation in advance as an azeotrope.

In the present invention, a phase transfer catalyst may be present in the reaction system. That is, the presence of a phase transfer catalyst has the advantage of increasing the reaction rate and shortening the reaction time.

As a phase transfer catalyst, crown compounds such as dibenzo-18-crown-6-ether, molecular weight
300 to 600 polyethylene glycol, etc. can be used.

The appropriate amount to be added is 0.01 mol to 0.25 mol relative to the tetrachlorocyanopyridine.

Benzonitrile, the solvent of the present invention, can be easily separated from the product by distillation and can be reused as a solvent in the next reaction.

EXAMPLES The present invention will be explained in more detail with reference to Examples below, but the present invention is not limited thereto.

Example 1 100 g of benzonitrile, 40 g (0.165 mol) of tetrachloro-3-cyanopyridine, and 46 g (0.790 mol) of dried potassium fluoride in the form of fine particles were charged into a 200 c.c. stainless steel autoclave, and the air inside the reaction vessel was charged. After replacing with nitrogen gas, 320℃
(13.5Kg/cm ² G) for 10 hours with stirring to react. After the reaction was completed, the reaction solution was separated from potassium chloride and unreacted potassium fluoride using a rotary evaporator under final conditions of an external temperature of 160° C. and a degree of vacuum of 20 Torr. When the separated liquid was analyzed using a gas chromatograph using a column packing material of SE52 of 1 m and a column bath temperature of 60°C, it was found that 79.4 mol% of tetrafluoro-3-cyanopyridine and 5-chloro- 5.1 mol% of 2,4,6-trifluoro-3-cyanopyridine was obtained. The separated liquid was purified using a precision fractionator to obtain 22 g of the desired product, tetrafluoro-3-cyanopyridine (at normal pressure).
165-166℃ fraction) was recovered. When this fraction was analyzed by gas chromatography, almost no peaks of compounds other than tetrafluoro-3-cyanopyridine were observed.

Example 2 Instead of tetrachloro-3-cyanopyridine,
The reaction mixture was placed in a 200 c.c. autoclave in the same manner as in Example 1, except that tetrachloro-4-cyanopyridine was used as the raw material, and the mixture was heated and stirred at 280° C. (8.0 Kg/cm ² G) for 15 hours to cause a reaction. After the reaction was completed, the mother liquor obtained in the same manner as in Example 1 was analyzed by gas chromatography, and it was found that 88.7 mol% of tetrafluoro-4-cyanopyridine was obtained based on the charged tetrachloro-4-cyanopyridine. By distilling the separated liquid, crystals of tetrafluoro-4-cyanopyridine (MP66
~67℃) was obtained.

Example 3 Dibenzo-18-crown-6-ether 3.8g
The raw materials were charged into a 200 c.c. autoclave in the same manner as in Example 1, except that (0.0106 mol) was dissolved in benzonitrile, and the raw materials were heated and stirred at 300° C. for 7 hours to react. After the reaction was completed, the mother liquor obtained in the same manner as in Example 1 was analyzed by gas chromatography.
67.3 mol% was obtained.

Example 4 Instead of tetrachloro-3-cyanopyridine,
The same procedure as in Example 1 was carried out except that tetrachloro-2-cyanopyridine was used as the raw material, and the mixture was charged into a 200 c.c. autoclave and heated and stirred at 230° C. (2.0 Kg/cm ² G) for 16 hours to react. After the reaction was completed, the mother liquor obtained in the same manner as in Example 1 was analyzed by gas chromatography, and it was found that 92.5 mol % of tetrafluoro-2-cyanopyridine was obtained based on the charged tetrachloro-2-cyanopyridine. By distilling the separated liquid, tetrafluoro-2-cyanopyridine was obtained as a fraction (60 mmHg) at 89-91°C.

Comparative Example 1 Same as Example 4 except that dimethylformamide was used instead of benzonitrile as the solvent.
The mixture was placed in an autoclave, and the temperature was raised to 190°C while stirring.

At the beginning of the temperature rise, the pressure was about 4 Kg/cm ² , but the pressure increased rapidly and reached 13 Kg/cm ² after about 3 hours. There was a tendency for the pressure to increase after that, and it was thought that the pressure was rapidly increasing due to a decomposition reaction caused by dimethylformamide, so the reaction was stopped.

When the reaction solution was cooled to room temperature and taken out after completion of the reaction, a large amount of tar-like material had been produced. When the mother liquor was analyzed by gas chromatography in the same manner as in Example 1, it was found that the raw material tetrachloro-2
Although almost no cyanopyridine was observed, only 47.4 mol% of tetrafluoro-2-cyanopyridine was obtained based on the charged tetrachloro-2-cyanopyridine.

Claims (1)

[Claims] 1. A process for producing tetrafluorocyanopyridines, which comprises reacting tetrachlorocyanopyridines with a fluorinating agent under spontaneous pressure in a benzonitrile medium at a temperature in the range of 190 to 400°C. . 2. The method according to claim 1, wherein the tetrachlorocyanopyridine is tetrachloro-3-cyanopyridine, and the tetrafluorocyanopyridine is tetrafluoro-3-cyanopyridine. 3. The method according to claim 1, wherein the tetrachlorocyanopyridine is tetrachloro-4-cyanopyridine, and the tetrafluorocyanopyridine is tetrafluoro-4-cyanopyridine. 4. Claims 1, 2 or 3, wherein the fluorinating agent is at least one selected from the group consisting of fluoride salts of alkali metals and alkaline earth metals.
Method described. 5. The method according to claim 1, 2 or 3, wherein the fluorinating agent is potassium fluoride. 6. The method according to claim 1, 2, 3, 4 or 5, wherein the reaction is carried out in the presence of a phase transfer catalyst.