WO2001042214A1

WO2001042214A1 - Method for producing optionally substituted 3-halopyridines

Info

Publication number: WO2001042214A1
Application number: PCT/EP2000/011784
Authority: WO
Inventors: Yuri Koptelov; Guido Steffan
Original assignee: Bayer Aktiengesellschaft
Priority date: 1999-12-08
Filing date: 2000-11-27
Publication date: 2001-06-14
Also published as: AU3154801A; DE19959026A1

Abstract

The invention relates to a method for producing optionally substituted 3-halopyridines, especially 3,5-dichloropyridine, according to which a polyhaloacetaldehyde is reacted with a (meth-)acrolein in the presence of a strongly polar solvent and in the presence of copper (I) chloride while forming a glutaric dialdehyde derivative, and said glutaric dialdehyde derivative is converted with an ammonia salt into an optionally substituted 3-halopyridine.

Description

Process for the preparation of optionally substituted 3-halopyridines

The present invention relates to a process for the preparation of optionally substituted 3-halopyridines, in particular 3,5-dichloropyridine. Optionally substituted 3-halopyridines are required as intermediates for the production of acaricides and insecticides.

It is known to use 3,5-dichloropyridine by chlorination of pyridine or

To produce pyridine hydrochloride (see e.g. J.C.S. 93, 1997 (1908)).

This process produces reaction genetics that are difficult to work up because they contain undesired isomers with similar boiling points as the target product and polychlorinated by-products. In addition, the selectivity lies

Formation of optionally substituted 3-halopyridines in only 15 to 27%. There is therefore a need for a process for the preparation of optionally substituted 3-halopyridines in which reaction mixtures which are easy to work up are obtained and, if possible, higher selectivities can also be achieved.

A process for the preparation of optionally substituted 3-halopyridines has now been found, which is characterized in that a polyhaloacetaldehyde with a (meth) acrolein in the presence of a strongly polar solvent and in the presence of copper (I) chloride Formation of a glutaraldehyde derivative is implemented and this is converted with an ammonium salt into an optionally substituted 3-halopyridine.

The polyhaloacetaldehyde and (meth) acrolein can also be used in the form of their acetals.

Examples of polyhaloacetaldehydes to be used are those of the formula

in the

Shark independently of each other for chlorine, bromine or iodine,

R for hydrogen, chlorine or bromine and

Y for oxygen or the rest -O-CH ₂ -CH ₂ -O-

stand.

Preferably both shark residues are the same and stand for chlorine. Furthermore, R is preferably hydrogen or chlorine and Y is preferably oxygen.

Chloral is particularly preferably used as the polyhaloacetaldehyde (formula (I); both shark and R = chlorine, Y = oxygen).

Examples of (meth) acroleins to be used are those of the formula

in the

R 'represents hydrogen or methyl and

Y has the meaning given for formula (I). Acrolein is preferably used (formula (II); R '= hydrogen, Y = oxygen).

For each mole of the respective polyhalogenaldehyde, the respective (meth -) -

Acrolein e.g. use in amounts of 0.8 to 1.2: 1 mol. It is preferred to take equimolar amounts.

The strongly polar solvents are e.g. Nitriles in question such as aceto-, propio- and benzonitrile. Acetonitrile is preferred. The amount of the highly polar solvent is not critical. Based on 1 mol of polyhalogenaldehyde, for example, 200 to 1000 ml of a strongly polar solvent can be used.

The copper (I) chloride can be based on 1 mole of the polyhaloaldehyde e.g. Use in amounts of 0.001 to 0.5 mol. This amount is preferably from 0.01 to 0.1 mol.

The reaction temperature for the formation of the glutardialdehyde derivative can e.g. are in the range of 80 to 150 ° C. Temperatures in the range from 100 to 130 ° C. are preferred.

The formation of the glutardialdehyde derivative can e.g. at pressures in the range of 1 to 10 bar. It is preferable to work in a closed, pressure-resistant vessel at which the pressure sets itself under the respective reaction conditions. One can also at higher than self-adjusting

Work printing, e.g. by injecting an inert gas such as nitrogen.

The reaction mixture present after the formation of the glutaraldehyde derivative generally contains monomeric and polymeric forms of the glutaraldehyde derivative formed. The reaction mixture can be used as such for the further reaction with an ammonium salt. However, it is preferred to remove the more volatile components from the reaction mixture before the reaction with an ammonium salt. In general, these are the solvent and unreacted starting materials, which can be removed, for example, by stripping off under reduced pressure. So removed

Solvents and unreacted starting materials can be used again, as separated or after purification (e.g. by distillation), to produce glutaraldehyde derivatives.

The glutardialdehyde derivatives can optionally be purified prior to reaction with ammonium salts, e.g. by mixing the entire reaction mixture, preferably the reaction mixture freed from solvent and more volatile constituents, with a non-polar solvent, e.g. Diethyl ether, toluene or petroleum ether are added to bring the glutardialdehyde derivatives into solution. You can then e.g. Separate copper salts and tars by filtration and remove the cleaned ones

Recover glutardialdehyde derivatives by stripping off the non-polar solvent.

The monomeric form of the glutardialdehydes obtained in the first reaction step corresponds, for example, to the formula

in which the symbols used have the meaning given for the formulas (I) and (II).

The reaction of the glutardialdehyde derivative with an ammonium salt can be carried out with or without a solvent, for example with ammonium chloride or Ammonium acetate can be carried out. Possible solvents to be used are, for example, water and acetic acid. It is preferred to work with ammonium chloride in aqueous solution or with ammonium acetate without a solvent or with ammonium acetate and acetic acid as a solvent. If dissolved ammonium salts are used, this solution can be, for example, 10 to 30% by weight.

Based on 1 mol of polyhalaldehyde originally used, for example 1.8 to 10, preferably 1.9 to 4, mol of ammonium salt can be used.

Suitable temperatures for the reaction with the ammonium salt are, for example, 60 to 130 ° C. If solvents are used, the process is preferably carried out under reflux, if solvents are not used, preferably at temperatures at which water and any acetic acid which is formed distill off.

The pH is preferably kept in the range from 1 to 5 during the reaction with the ammonium salt.

The reaction with the ammonium salt can e.g. carry out such that the reaction mixture obtained in the first reaction stage, the reaction mixture freed from the solvent and unreacted starting products for the first reaction stage or purified glutardialdehyde derivatives are mixed with the ammonium salt which may be dissolved, or the ammonium salt which is optionally dissolved is introduced and the glutardialdehyde derivatives are gradually introduced in one of the forms described after adds.

The reaction mixture present after the second reaction stage can be worked up, for example, by first cooling it, e.g. to 20 to 40 ° C, then a pH of 4 to 8, preferably 5 to 6.5

(eg by adding aqueous sodium hydroxide solution), then diluted with water and finally the optionally substituted 3-halopyridine produced is distilled off together with steam. During the distillation, it is advantageous to control the pH and to keep it, for example by adding aqueous sodium hydroxide solution, to values of, for example, 6 to 8. The optionally substituted 3- separated from the reaction mixture can be removed from the distillate.

Halogenpyridine obtained, for example, by neutralizing, filtering off the precipitate formed, washing and drying in pure form.

The optionally substituted 3-halopyridines produced can, for example, correspond to the formula (IV)

in the

R "represents hydrogen, methyl or shark and

In both cases, shark is independently chlorine, bromine or iodine.

3,5-dichloropyridine is preferably prepared according to the invention.

The process according to the invention has the advantages that the optionally substituted 3-halopyridines which are prepared can be removed from the reaction mixture in a simple manner, for example by means of steam distillation, and the yield is better than in the known processes. Examples

example 1

A mixture of 2 mol of anhydrous chloral, 2 mol of acrolein, 0.1 mol of copper (I) chloride and 600 ml of anhydrous acetonitrile was heated in an enamelled autoclave to 120 ° C for 6 hours and the pressure in the range 3 to 4 under a nitrogen atmosphere Held at 5 bar. After cooling and stripping off the solvent and unreacted starting materials at 10 mbar and a bath temperature up to 45 ° C., a mixture was obtained which contained monomeric and polymeric forms of the corresponding glutardialdehyde derivative. This mixture was mixed with a solution of 4 moles of ammonium chloride in 220 ml of water and heated to reflux at normal pressure for 2.5 hours. The mixture was then cooled, a pH of 6 was established in the reaction mixture by adding aqueous sodium hydroxide solution, diluted with 300 ml of water and obtained directly from the

A steam distillation was carried out in the reaction vessel, the pH of the bottoms being kept above 6. The distillate was neutralized, the precipitate was purified by filtration, isolated, washed with a little ice water and dried, giving 3,5-dichloropyridine in a yield of 33.4%.

Example 2

The first step of Example 1 up to and including stripping off the solvent and unreacted starting materials was repeated. Then 4 mol of ammonium acetate were added and the mixture was heated for 2.5 hours until

Distill off water and acetic acid. The mixture was then cooled, a pH of 6 was established in the reaction mixture by adding aqueous sodium hydroxide solution, diluted with 300 ml of water and steam distillation was carried out directly from the reaction vessel, the pH in the sump being kept above 6. After diluting the distillate with twice the volume of water, Filtration, washing with a little ice water and drying gave 3,5-dichloropyridine in a yield of 30.3% of theory.

Claims

claims

1. A process for the preparation of optionally substituted 3-halopyridines, characterized in that reacting a polyhaloacetaldehyde with a (meth) acrolein in the presence of a strongly polar solvent and in the presence of copper (I) chloride to form a glutardialdehyde derivative and this is converted into an optionally substituted 3-halopyridine with an ammonium salt.

2. The method according to claim 1, characterized in that the to be used

Polyhaloacetaldehyde corresponds to formula (I)

in the

Shark independently of each other for chlorine, bromine or iodine,

R for hydrogen, chlorine or bromine and

Y for oxygen or the rest -O-CH ₂ -CH ₂ -O-

stand,

and the (meth) acrolein to be used corresponds to the formula (II)

in the R 'represents hydrogen or methyl and

Y has the meaning given for formula (I).

3. The method according to claims 1 and 2, characterized in that one

Uses chloral and acrolein and produces 3,5-dichloropyridine.

4. Process according to Claims 1 to 3, characterized in that 0.8 to 1.2 moles of (meth) acrolein and 0.01 to 0.5 moles of copper (I) chloride are used per mole of the respective polyhalaldehyde.

5. Process according to Claims 1 to 4, characterized in that the reaction temperature for the formation of the glutardialdehyde derivative is 30 to 150 ° C and the pressure is 1 to 10 bar.

6. Process according to Claims 1 to 5, characterized in that the more volatile components are removed from the reaction mixture before the reaction with an ammonium salt.

7. The method according to claims 1 to 6, characterized in that one uses ammonium chloride or ammonium acetate and water or acetic acid as the optional solvent.

8. The method according to claims 1 to 7, characterized in that one per

Mol uses 1.8 to 10 moles of ammonium salt originally used polyhalaldehyde.

9. The method according to claims 1 to 8, characterized in that the reaction with the ammonium salt at 60 to 130 ° C and at pH values in

Performs range 1 to 5.

0. Process according to Claims 1 to 9, characterized in that the reaction mixture present after the second reaction stage is worked up by cooling it, then adjusting a pH of 4 to 8, then diluting it with water and finally the optionally substituted 3rd prepared -Halogen pyridine distilled off together with steam.