HU182692B - Process for preparing fluoro-pyridine compounds - Google Patents

Abstract

The present invention relates to an improved process for the preparation of fluoropyridine compounds by reaction of the corresponding chloropyridine compounds of formula (I), wherein n is 1, 5, 2, 3, 4 or 5, and an molar excess of alkali metal fluoride. comprising reacting the reaction with the amount of fluoride theoretically required to produce the desired fluoropyridine compound in an amount of from 0.1 to 0.5 mol of alkali metal fluoride and from 0.5 to 10% by weight based on the amount of alkali fluoride; in the presence of a halide of an iron group, in the absence of a solvent, at a temperature of between 250 ° C and 350 ° C, whereby one or more chlorine atoms of the chloropyridine-15 compound are replaced by a fluorine atom. The advantage of the process compared to known methods is that fluoropyridine compounds are produced in lower yields with lower alkali metal fluoride at lower temperatures. (I) 182692

Description

The present invention relates to an improved process for the preparation of fluoropyridine compounds by reacting the corresponding chloropyridine compounds with alkali metal fluorides. The fluoropyridine compounds of the present invention are useful as intermediates in the preparation of pesticidal, in particular herbicidal, active ingredients.

It is known that the reaction of chloropyridine compounds with potassium fluoride in a polar aprotic solvent in the presence of a small amount of water may result in the exchange of the chlorine atom with a fluorine atom, such as pentachloropyridine in anhydrous potassium fluoride Reaction with (95.8%) yields a pure product of 91% 3,5-dichlorotrifluoropyridine, 6% 3-chlorotetrafluoropyridine and 3% 3.4, Contains 5,6-tetrachlorofluoropyridine (British Patent No. 1,256,082). Reaction of pentachloropyridine and potassium fluoride in a 1:11 molar ratio at 400 ° C for 18 hours in the absence of solvent afforded 84%

3,5-dichloro-2,4,6-trifluoropyridine (J. Chem. Soc., 354, 1964). Reaction of pentachloropyridine with potassium fluoride in a 1: 9.5 molar ratio at 400 ° C for 5 hours in the absence of solvent gave 45% yield of 3,5-dichloro-2,4,6-trifluoropyridine and 19% yield of 3- chlorotetrafluoropyridine is formed (J. Chem. Soc., 1965, 594).

It has been found that fluoropyridine compounds can be prepared in good yields, but using less alkali metal fluoride and at lower temperatures, by reacting the corresponding chloropyridine compound with a molar excess of alkali metal fluoride to form metal halides of the iron group. is carried out in the presence of a catalytic amount of one of these. At least one of the chlorine atoms of the chloropyridine compound is replaced by a fluorine atom. The desired product can then be isolated by distillation.

Accordingly, the present invention relates to an improved process for the preparation of fluoropyridine compounds by reacting the corresponding chloropyridine compounds of formula I wherein n is 1, 2, 3, 4 or 5 with a molar excess of alkali metal fluorides, which comprises carrying out the reaction in the presence of 0.5 to 10% by weight, based on the amount of alkali metal fluoride, of the halogenated metal of the iron group in the absence of a solvent at a temperature of 250 to 350 ° C. its chlorine atom is replaced by a fluorine atom.

In the process of the present invention, the starting compound can be any pyridine compound of formula (I) wherein n is from 1 to 5 substituted with at least one chlorine atom, such that the chloropyridine compounds include the mono-, di-, tri-, tetra- and pentachloropyridine compounds. The starting compound is selected according to the number of times the substituted fluorine compound is desired. Thus, it is convenient to start from pentachloropyridine for the trifluoro compound and from tetrachloropyridine for the difluoro compound. If the starting compound is a polychloropyridine compound, the number of fluorine-substituted chlorine atoms is believed to depend on the temperature and time of the reaction, with higher temperatures and longer reaction times favoring greater substitution.

The process of the present invention is of particular interest for 3,5-dichloro-2,4,6-trifluoropyridine pentachloropyridine, 3,5-dichloro-2,6-difluoropyridine 2,3,5,6-tetrachloride. pyridine bcl and 2,6-difluoropyridine starting from 2,6-dichloropyridine.

The alkali metal fluoride used in the process of the invention is cesium, potassium or sodium fluoride, of which potassium fluoride is preferred.

As previously mentioned, the use of a molar excess of alkali metal fluoride is an essential parameter. The excess amount of alkali metal fluoride used is preferably 0.1 to 1 mole, more preferably 0.1 to 0.5 mole, relative to the amount of fluoride theoretically required to form the desired fluoropyridine compound.

The catalysts used in the process of the present invention are bromide or chloride of the metals of the iron group. The most preferred catalyst is ferric chloride. Of course, in order to provide the benefits of the invention, it is necessary to use the catalyst in an amount that will truly exert a catalytic effect. In view of the overall economy and technology, the catalyst is generally employed in an amount of 0.5 to 10% by weight, preferably 1 to 5% by weight, and particularly preferably 1 to 3% by weight, based on the amount of alkali metal fluoride.

For reasons of economy it is generally convenient to carry out the reaction according to the invention without the use of a solvent, although a solvent such as sulfolane may also be used.

Although the process of the invention can be successfully carried out in a glass apparatus, it is well known that glass is sensitive to alkali metal fluorides and therefore, when using a glass apparatus, it may be desirable to use higher amounts of the alkali metal fluoride than the previously mentioned preferred amounts. Therefore, it is advantageous to carry out the process in an apparatus whose parts in contact with the reagents are made of an inert material, such as stainless steel, nickel or Hastelloy C alloy, against alkali metal fluorides.

The reaction conditions provided in the practice of the process of the invention are such that the reagents are in liquid or gaseous state. Reagents below 150 ° C have a tendency to form a solid, so the reaction is preferably carried out at 150 ° C to 400 ° C, more preferably 250 ° C to 350 ° C, and most preferably 250 ° C to 300 ° C. The reaction is carried out in a sealed vessel in which the overpressure formed is dependent on the reaction temperature and the molar number of starting materials. At 300 ° C, the pressure is typically 4.4 atm and

14.6 atm.

In a particularly preferred embodiment of the process according to the invention, pentachloropyridine is reacted with 3.3 to 4.5 moles of potassium fluoride per mole of 1 to 3% by weight of iron (III) 3 per mole of potassium fluoride in a sealed reaction vessel.

-2182692

in the presence of chloride and in the absence of solvent at 250 ° C to 350 ° C, the 3,5-dichloro-2,4,6-trifluoropyridine formed as the main product is isolated.

As mentioned above, the fluoropyridine compounds of the present invention are used primarily in the preparation of agricultural fluoropyridine derivatives. Examples of agriculturally useful fluoropyridine derivatives obtained using the fluoropyridine compounds obtainable by the process of the present invention are, first, compounds of formula II wherein X is independently chlorine, bromine or fluorine.

R is -CONR ¹ R ² (R ¹ and R ² in this group)

R ^{2 is} independently hydrogen or

1-8 carbon atoms), -COOH or -COOR ³ (in this tube, R ³ is alkyl having 1 to 12 carbon atoms or - (CH ₂ ) _n OR ⁴ , and in the latter n) 2, 3 or 4, while R ^{4 is} alkyl or phenyl having from 1 to 6 carbon atoms] and

M is hydrogen or alkyl having 1 to 6 carbon atoms and salts of compounds of formula II wherein R is -COOH. Such compounds, as well as agricultural compositions containing these compounds, are described in British Patent No. 1,418,979.

The compounds of formula (III) and (IV) may also be mentioned as agriculturally useful fluoropyridine derivatives. The compounds of formula (II) and the compound of formula (III) are herbicidal and the compound of formula (IV) are nematocidal.

The agriculturally useful fluoropyridine compounds of the fluoropyridine compounds of the present invention may be prepared by methods well known in the art of organic chemistry. By way of example, reference is made to the reaction acid shown in Scheme A (wherein R ³ is as defined above). It will be appreciated by those skilled in the art that there are many other routes for the production of agriculturally useful fluoropyridine derivatives from the fluoropyridine compounds of the present invention.

The following examples and comparative examples are intended to illustrate the invention.

Example 1

A mixture of 100 g of potassium fluoride and 1 g of ferric chloride is prepared by grinding the two components. Similarly, a mixture of 2 g (0.008 mol) of pentachloropyridine and 1.87 g of potassium fluoride / ferric chloride (corresponding to 0.032 mol of potassium fluoride), measured from the above mixture, is prepared. The mixing operations are carried out under a dry nitrogen atmosphere. The reagent mixture is then transferred to a stainless steel cylinder and the cylinder sealed. The cylinder and its contents are then stored in an oven at 300 ° C for 16 hours. After cooling, the contents of the cylinder were extracted with chloroform and the extract was filtered. According to gas chromatography analysis a

The yield of 3,5-dichloro-2,4,6-trifluoropyridine was 87%, while that of 3-chloro-2,4,5,6-tetrafluoropyridine was 4%.

Example 2

The procedure described in Example 1 is essentially the same, except that the mixture of reagents contains 3.74 g of potassium fluoride-ferric chloride (corresponding to 0.064 moles of potassium fluoride), i.e. a molar ratio of potassium fluoride to pentachloropyridine of 8: 1; the reactor is made of glass; finally, the reactor contents were kept at 340 ° C for 30 hours. Thus, 2,3,4,5-tetrachloro-6-fluoropyridine (31%), 2,3,5-trichloro-4,6-difluoropyridine (57%) and 3% (8%) were obtained. 5-Dichloro-2,4,6-trifluoropyridine is formed.

Example 3

The procedure described in Example 1 was followed except that the mixture of reagents contained 1.62 g of potassium fluoride-ferric chloride mixture (corresponding to 0.028 moles of potassium fluoride); and the reaction temperature is 250 ° C. Thus 2,3,4,5-tetrachloro-6-fluoropyridine in 2% yield, 2,3,5-trichloro-4,6-difluoropyridine in 24% yield and 3.5% in 61% yield. -dichloro-2,4,6-trifluoropyridine is formed.

Example 4 (Comparative Example)

The reaction described in Example 3 is repeated, but the iron (III) chloride catalyst is not used. Thus, 5% of unreacted pentachloropyridine is left, while the yields of 2,3,4,5-tetrachloro-6-fluoropyridine are 38%, the yield of 2,3,5-trido-4,6-difluoropyridine is 33% and the

3,5-dichloro-2,4,6-trifluoropyridine 17%.

Example 5

The procedure described in Example 1 was followed except that the mixture of reagents contained 2 g (0.0092 mol) of 2,3,5,6-tetrachloropyridine. Yield 70%

3,5-dichloro-2,6-difluoro-pyridine.

Example 6 (Comparative Example)

The reaction described in Example 5 is repeated, but the iron (III) chloride catalyst is not used. Thus, 1% of unreacted 2,3,5,6-tetrachloropyridine remains, while 22% yields 2,3,5-trichloro-6-fluoropyridine and 61% yield 3,5-dichloro-2 6-difluoropyridine is formed.

Claims (4)

Patent claims: A process for the preparation of fluoropyridine compounds by reacting the corresponding chloropyridine compounds of formula (I) wherein n is 1, 2, 3, 4 cut-offs and excess alkali metal fluorides with characterized in that the reaction is carried out in a catalytic amount of 0.5 to 10% by weight, relative to the amount of fluoride theoretically required for the formation of the desired fluoropyridine compound, in an excess of 0.1 to 0.5 molar alkali metal fluoride and 0.5 to 10% by weight of alkali metal fluoride. in the absence of a solvent at temperatures between 250 ° C and 350 ° C 5 finally. 2. A process according to claim 1 wherein the alkali metal fluoride is potassium fluoride. 3. A process according to claim 1 or 2 wherein the catalyst is 1-3% by weight of ferric chloride based on the amount of potassium fluoride. 4. A process according to any one of claims 1 to 3, wherein the starting compound is pentachloropyridine or 2,3,5,6-tetrachloropyridine.