JPH0149339B2 - - Google Patents

Description

[Detailed Description of the Invention] [Industrial Field of Application] The present invention provides a new substance, 2,2-dichloro-
Regarding 3,3,3-trifluoropropionaldehyde and its production method, this new substance is particularly applicable to 4-formyl-2,4-dichloro-5,5,5
-Used in the synthesis of trifluorovaleronitrile and 2,3-dichloro-5-trifluoromethylpyridine.

[Prior Art] Chlorpyridines substituted with a methyl group, trichloromethyl group or trifluoromethyl group are
Conventionally, they were manufactured only by methods that required multiple steps. For example, 2,5-dichloro-3-methylpyridine and 2,3-dichloro-5-methylpyridine are each 2-chloro-3-methyl-5
-It was produced by diazotizing aminopyridine or 2-chloro-3-amino-5-methylpyridine and replacing it with chlorine while decomposing it.

The above aminopyridine is obtained by chlorinating 3-methylpyridine to produce 2-chloro-3-methylpyridine and 2-chloro-5-methylpyridine, and by nitration, these are converted to 2-chloro-3-methyl-5-
Nitropyridine and 2-chloro-3-nitro-
It can be produced by reducing a nitro compound to 5-methylpyridine. Chlorination of 3-methylpyridine usually produces a number of isomers in addition to the desired compound. By chlorination of 2,3-dichloro-5-methylpyridine, 2,3-
Dichloro-5-trichloromethylpyridine can be obtained and converted to 2,3-dichloro-5-trifluoromethylpyridine by replacing the chlorine atom of the trichloromethyl group with a fluorine atom (for example, as described in European Patent Publication No. (See No. 004414). Also,
By heating 2,4-dimethylpyrrole and chloroform in the gas phase at a temperature of about 550°C, 2-
Chlor-3,5-dimethylpyridine is obtained together with five other isomers (J.Chem.Soe.Perkin
Trans.I, 1578-82 (1979)).

(Problem to be solved by the invention) The following formula (In the formula, R is chlorine and R ¹ is a methyl or trifluoromethyl group, or R is a methyl, trichloromethyl or trifluoromethyl group and R ¹
represents a methyl group, or R and R ¹ represent a methyl group. 2,3-dichloro-5-trifluoromethylpyridine, represented by It has been newly discovered that it can be manufactured using raw materials.

That is, in the presence of a catalyst, a) trichloroacetaldehyde is added to methylacrylonitrile or α-trifluoromethylacrylonitrile, or b) 2,2-dichloropropionaldehyde,
Pentachlorpropionaldehyde or 2,
By adding 2-dichloro-3,3,3-trifluoropropionaldehyde to acrylonitrile, or c) by adding 2,2-dichloropropionaldehyde to methacrylonitrile, the following formula is generated: (In the formula, R is chlorine and R ² is a methyl or trifluoromethyl group, or R is a methyl, trichloromethyl group or trifluoromethyl group.
R ² represents hydrogen or R and R ² represent a methyl group. ) It can be produced by a method of cyclizing an intermediate product shown in the formula to form a compound of the formula.

A formally identical reaction to obtain 2,3,5-trichloropyridine from non-alkyl-substituted trichloroformbutyronitrile was published in European Patent Publication No.
Described in No. 12117. However, formylbutyronitrile of the formula substituted by a chlorinated methyl group or trihalogenated methyl group is cyclized to a chlorinated methyl group or trihalogenated methylpyridine of the formula while being aromatized. That could not have been predicted. This is because by the method of the invention it is no longer possible to carry a methyl or trihalogenated methyl group on the ring and perform the elimination of water necessary for aromatization. Therefore, the predicted organism was rather a 2-pyridone derivative. The results of the above method are therefore very surprising. The formation of adduct compounds of the formula from 2,2-dichloro-propionaldehyde, perchlor- or 2,2-dichloro-3,3,3-trifluoropropionaldehyde also shows that the reactivity of trichloroacetaldehyde is greater than that of its congeners. very different from the body (e.g. Chem.Ber., 97 , 3322
(1964)], which is surprising especially since the mobility of chlorine in chloroacetaldehyde is considerably limited by other hydrocarbon substituents such as methyl, trichloromethyl or trifluoromethyl.

By this method, 2,3-dichloro-5 was obtained via 4-formyl-2,4-dichloro-5,5,5-trifluorovaleronitrile as an intermediate product.
-2,2-dichloro-3,3,3, which is a raw material for producing trifluoromethylpyridine
- Trifluoropropionaldehyde and the method for producing the substance were previously unknown.

[Means for solving problems]

The present invention provides a new substance, 2,2-dichloro-3,3,3-trifluoropropionaldehyde, and a method for producing the same.

The method for producing 2,2-dichloro-3,3,3-trifluoropropionalhyde of the present invention comprises 4,
4-dichlor-5,5,5-trifluoro-2-
Methyl-2-pentenecarboxylic acid is subjected to ozonolysis and then an aqueous suspension of zinc dust is added to the reaction mixture to distill 2,2-dichloro-3,3,3-trifluoropropionaldehyde. This is a characteristic feature.

[Preferred mode for carrying out the invention]

2,2-dichloro-3,3,3- according to the invention
The following are used as solvents in the process for producing trifluoropropionaldehyde: organic acids such as formic acid, acetic acid, propionic acid; esters of these acids such as ethyl acetate, methyl acetate, methyl formate, methyl formate. Esters: aliphatic hydrocarbons, such as pentane, hexane, heptane, octane, cyclopentane, cyclohexane; chlorinated hydrocarbons, such as methylene chloride, chloroform, carbon tetrachloride; water.

The reaction temperature depends on the nature of the solvent, but ranges from -90℃ to +
70°C, preferably -70°C to +30°C.

In one preferred embodiment of this ozonolysis method, 4,4-dichloro-5,5,5-trifluoro-2-methyl-2-pentenecarboxylic acid methyl ester is ozonated in acetic acid at 20°C, and then reacted. An aqueous suspension of zinc dust is added to the mixture, and 2,2-dichloro-3,3,3-trifluoropropionaldehyde is directly distilled from the mixture.

Hereinafter, the above-mentioned novel method for producing chlorpyridines of the formula containing 2,3-dichloro-5-trifluoromethylpyridine will be explained.

The addition reaction in this method is carried out in an open or closed system, preferably at a temperature of 70 to 160°C. Preferably, the addition reaction is carried out in a closed system under a pressure corresponding to the reaction temperature, for example in the range from 1 to 30 bar.

Metals from the main group and subgroups a, a, b and b of the periodic table, such as iron, cobalt, nickel, ruthenium, palladium, chromium, molybdenum, manganese, copper and zinc, are used as catalysts for the above addition reaction. can do. These metals can be used both in their elemental state and in their compound state. Suitable compounds are, for example, oxides and salts such as halides, sulphates, sulphites, sulphides, sulphates, acetates, stearates, citrates, carbonates, cyanides, rhodanides, and phosphines. It is a chain with a ligand such as phosphites, benzoylacetone, acetylacetone, nitriles, isonitriles, and carbon monoxide.

Typical examples include:
Copper () oxide, iron () oxide; copper copper ()
-, copper () -, iron () - and iron () bromide, - iodide and especially - chloride, zinc chloride,
and chlorides of ruthenium, rhodium, palladium, cobalt and nickel; copper () sulphates,
Iron () - and iron () sulfate; copper () sulfate and iron () sulfate; manganese () acetate, copper () acetate, copper () steriaphosphate, iron () citrate, copper () Cyanide;
Ruthenium ()-dichloro-tris-triphenylphosphine, rhodium-dichloro-tris-
triphenylphosphine; chromium- and nickel acetylacetonate; copper ()-acetylacetonate; iron ()-acetylacetonate; cobalt ()-- and cobalt ()-acetylacetonate; manganese ()-acetylacetonate; copper ()- Benzoylacetonate; iron carbonyl-cyclopentadienyl complex; molybdenum carbonyl cyclopentadienyl complex, chromium tricarbonylaryl complex, ruthenium ()-acetate complex, chromium- and molybdenum hexacarbonyl, nickel tetracarbonyl, iron pentacarbonyl, cobalt - and manganese carbonyl.

Mixtures of the above-mentioned metals with metal compounds and/or other additives, such as combinations of copper powder and one of the above-mentioned copper compounds; copper powder and lithium halides (such as lithium chloride) or isocyanides (tert-
(butyl isocyanide, etc.); mixtures of iron powder and iron () chloride, sometimes with the addition of carbon monoxide; mixtures of iron () chloride and benzoin; iron () - or iron () Mixtures of chlorides and trialkyl phosphites; mixtures of iron pentacarbonyl and iodine can also be used.

Preference is given to iron() and iron() salts and complexes, in particular iron()- and iron() chlorides, and iron powder; ruthenium() chloride, ruthenium() dichloro-tris-triphenylphosphine. , copper powder, bronze, copper() and copper() salts and complexes, such as copper() chloride,
Copper () chloride, Copper () bromide, Copper () bromide, Copper () acetate, Copper () acetylacetonate, Copper () benzoylacetonate, Copper () sulfate, Copper () sulfate, Copper () ) cyanide and copper () iodide.

Particularly preferred are copper powder, bronze, copper () - and copper () chloride or - bromide and copper ()
iodide, as well as mixtures thereof.

The catalyst usually has a concentration of about 0.01 to aldehydes.
It is used in an amount of 10 mol%, preferably 0.1-5 mol%.

Acrylonitrile, methacrylonitrile or α-trifluoromethyl of the above-mentioned aldehydes
The addition to acrylonitrile is preferably carried out in the presence of an inert organic solvent. A suitable solvent should be one that sufficiently dissolves the catalyst or is capable of forming a complex with the catalyst.
It is inert to the reaction components. Examples of suitable solvents include: Alkanecarboxylic acid nitriles, especially those having 2 to 5 carbon atoms
3-alkoxypropionitriles in which the alkoxy group has 1 to 2 carbon atoms, such as 3-ethoxypropionitrile and 3-ethoxypropionitrile; aromatic nitriles, especially Benzonitrile; preferably aliphatic ketones having 3 to 8 carbon atoms, such as acetone, diethyl ketone, methyl isopropyl ketone, diisopropyl ketone, methyl-tert-butyl ketone;
Alkyl and alkoxyalkyl esters of aliphatic monocarboxylic acids having 2 to 6 carbon atoms, such as methyl formate and ethyl ester, methyl acetate, ethyl, n-butyl and
Isobutyl ester and 1-acetoxy-2-
Methoxyethane; cyclic ethers such as tetrahydrofuran, tetrahydropyran and dioxane; dialkyl ethers in which the alkyl group has 1 to 4 carbon atoms, such as diethyl ether, di-n-propyl ether and diisopropyl ether; N,N-dialkylamides of 1 to 3 alkanecarboxylic acids, such as N,N-dimethylformamide, N,N-dimethylacetamide, N,N-diethylacetamide and N,N-dimethylmethoxyacetamide; carbon atoms of the alkyl group Ethylene glycol and diethylene glycol dialkyl ethers each having a number from 1 to 4, such as ethylene glycol dimethyl, diethyl and di-n-butyl ether: diethylene glycol diethyl and di-n-butyl ether; tris-N phosphoric acid , N-dimethylamide (Hexametapol). Furthermore, excess acrylonitrile, methacrylonitrile or α-trifluoromethylacrylonitrile can also be used as a solvent.

Preferred solvents for the addition reaction are alkanecarboxylic acid nitriles with 2 to 5 carbon atoms and 3-alkoxypropionitriles with an alkyl group of 1 to 2 carbon atoms, especially acetonitrile, butyronitrile and 3-methoxypropionitrile,
or unsaturated nitriles used as reaction components.

The intermediate product of the formula is also a new substance.

The cyclization of compounds of the formula is carried out in open or closed systems at temperatures of about 0 to 220°C, especially about 100 to 200°C.
Preferably the cyclization is carried out in an open system. During the cyclization in the open system, in the presence of hydrogen chloride or with substances that form hydrogen chloride under the reaction conditions, such as phosgene,
It is convenient to carry out the reaction in the presence of boron trichloride, aluminum chloride, trialkylammonium chloride whose alkyl group has 1 to 4 carbon atoms, phosphorus pentachloride, phosphorus oxychloride or phosphorus trichloride. Preferably the cyclization is carried out in the presence of hydrogen chloride.

The cyclization is preferably carried out by simply heating the compound of the formula in the liquid or gas phase without the addition of a solvent. However, the cyclization can also be carried out in the presence of organic solvents. Examples of organic solvents include chlorinated aliphatic hydrocarbons such as chloroform, methylene chloride and tetrachloroethane; optionally chlorinated aromatic hydrocarbons such as benzene;
Toluene, xylene and chlorobenzene; N,N- of alkanecarboxylic acids having 1 to 3 carbon atoms
dialkylamides, such as N,N-dimethylformamide, N,N-methylacetamide, N,N
-diethylacetamide and N,N-dimethylmethoxyacetamide; cyclic amides such as N-
Methyl-2-pyrrolidone, N-acetyl-2-pyrrolidone and N-methyl-ε-caprolactam; amides of carbonic acids, such as tetramethylurea and dimorpholinocarbonyl; phosphorous acid, phosphoric acid, phenylphosphonic acid or carbon of alkyl groups Amides of alkylphosphonic acids having 1 to 3 atoms, such as phosphoric triamimide, phosphoric acid-tris(N,N
-dimethylamide), trimorpholide phosphate, trivirolinide phosphate, tris-phosphorous acid (N,
Amides of sulfuric acid or aliphatic or aromatic sulfonic acids, such as tetramethylsulfamide, methanesulfonic acid dimethylamide or p-toluene Sulfonic acid amides; aliphatic ketones, cyclic ethers, dialkyl ethers, and ethylene glycol- and diethylene glycol ethers of the type mentioned above, as well as phosphorus trichloride and phosphorus oxychloride.

Preferred solvents for the cyclization are chloroform, methylene chloride, cyclic ethers and diethyl ether in which the alkyl group has 1 to 4 carbon atoms, respectively;
in particular dioxane and diethyl ether, and N,N of alkanecarboxylic acids having 1 to 3 carbon atoms.
- dialkylamides, especially N,N-methylformamide.

This conventional process for the preparation of chlorpyridines can be carried out advantageously by first isolating the compound of formula produced in the addition reaction and then cyclizing it in a second reaction step. In this case, the individual reaction steps are carried out as described above.

According to a preferred embodiment, the aforementioned aldehydes are treated in a closed system with acetonitrile as a solvent,
Copper powder, bronze, copper () or copper () chloride or bromide, in butyronitrile or 3-methoxypropionitrile at a temperature of 70 to 160 °C,
or iodide of copper (), or reacted with acrylonitrile, methacrylonitrile or α-trifluoromethyl-acrylonitrile in the presence of 0.1 to 5 mol% of a mixture of these substances, and after separation of the solvent the resulting formula 100 compounds in open system
Cyclization in the presence of hydrogen chloride or a substance that forms hydrogen chloride under the reaction conditions at a temperature of ~200°C gives a compound of formula.

However, it is also possible to carry out the addition reaction and the cyclization reaction in one operation without isolating the intermediate product of the formula. In this case, the reaction to obtain the chlorpyridine of formula from aldehyde and acrylonitrile, methacrylonitrile or α-trifluoromethyl-acrylonitrile is carried out at 70-220°C, especially at 130-220°C.
Preferably it is carried out at a temperature of 200°C. At this time, it can be carried out either in an open system or in a closed system. When the reaction is carried out in an open system, it is preferably carried out in the presence of hydrogen chloride or in the presence of a substance that forms hydrogen chloride under the reaction conditions. Such substances are, for example, phosgene, boron trichloride, aluminum chloride, trialkylammonium chlorides in which the alkyl group has in each case 1 to 4 carbon atoms, phosphorus pentachloride, phosphorus oxychloride or phosphorus trichloride. The one-stage preparation of chlorpyridine of the formula is preferably carried out in a closed system under a pressure corresponding to the reaction temperature at hand, ie in the range, for example, from 1 to 50 bar. It is particularly preferred that the synthesis of the compounds of the formula in one step is carried out in a closed system at a pressure of 1 to 30 bar.

This one-step synthesis is also advantageously carried out in the presence of a catalyst and in the presence of an inert organic solvent. Catalysts and solvents include those of the first-mentioned type mentioned in connection with preferred catalysts and catalyst amounts.

Preferred solvents for processes carried out in one step are alkanecarboxylic acid nitriles having 2 to 5 carbon atoms and 3-alkoxypropionitriles having 1 to 2 carbon atoms in the alkyl group. Particularly suitable solvents are acetonitrile, butyronitrile and 3-methoxypropionitrile or excess unsaturated nitriles used as reaction components. After the reaction is completed, chlorpyridine of the formula can be prepared by the usual method,
For example, by distilling off the solvent and distilling the crude product,
In some cases, it can be isolated by steam distillation.

According to a further advantageous embodiment, the aldehyde and acrylonitrile, methacrylonitrile or α-trifluoromethylacrylonitrile are combined in a closed system with the solvent acetonitrile, butyronitrile or
- Copper powder, bronze, copper () or copper () chloride or bromide in methoxyproponitrile,
or copper () iodide, or in the presence of 0.1-5 mol% of a mixture of these substances, 130-200
℃ under a pressure corresponding to the reaction temperature at the time to give chlorpyridines of the formula.

Chlorpyridines of the formula 2,3-dichloro-5-trifluoromethylpyridine can be used for the production of various active substances, in particular for the production of pesticides and herbicides, in a known manner via one or more intermediate steps. (e.g. Swiss Patent No. 622170, European Patent Application No. 00176, European Patent Application No. 00483 and European Patent Application No. 04414; European Patent Application No. 818101818)
No.; German Publication No. 2812649 and German Publication No. 2812649;
No. 2748636: South African Patent No. 7802440; Japanese Patent Publication No. 54-115380, No. 55-038356, No. 55-
079369 and 56-39069 and Belgian Patent Specification No. 862325).

[Embodiments of the invention]

The present invention will be explained in more detail with reference to the following Reference Examples and Examples.

Reference example 1 a) 4-formyl-2-methyl-2,4,4-
Production of trichlorobutyronitrile 14.7 g of trichloroacetaldehyde, 13.5 g of methacrylonitrile and copper powder (Org.Synth.
Coll. Vol., 339), 0.3 g of the bronze was heated with 30 ml of acetonitrile in an enamel autoclave for 15 hours. After cooling, the solvent was distilled off at about 40-50° C. under reduced pressure using a water pump. Add 50ml of diethyl ether to the residue,
The precipitated copper sludge was filtered off. After distilling off the diethyl ether, the residue was rectified under high vacuum. A fraction boiling at 76-78 °C at 13 pa was collected. 4-formyl-2-methyl-2,4,4-
13.8 g of trichlorobutyronitrile was obtained as a colorless oil.

IR-spectrum (liquid film): 2250 (CN), 1750
(CO)cm ^{-1 1} H-NMR-spectrum (60MHz, CDCl ₃
middle): 9.3 (s, 1H, -CHO); 3.22 (s, 2H, C
-3H ₂ ): 2.60 (s, 3H, -CH ₃ ) ppm.

Elemental analysis as C ₆ H ₆ Cl ₃ NO (molecular weight 214.48): Calculated value C33.60% H2.82% N6.53% Cl49.59% Actual value C34.1% H3.1% N6.8% Cl48.6 % b) 4-formyl-2- obtained according to Reference Example 1a) for the production of 2,5-dichloro-3-methylpyridine
21.4 g of methyl-2,4,4-trichlorobutyronitrile were heated to 145° C. for 4-5 hours while introducing a weak stream of dry HCl gas. After cooling, the blackish melt was steam distilled. 9.9 g of 2,5-dichloro-3-methylpyridine was obtained as colorless crystals.

Melting point: 42°C (recrystallized from CH ₃ OH/H ₂ O volume ratio 4:1).

¹ -NMR-spectrum (60MHz, in CDCl ₃ ):
8.15 (d, 1H, H of C-6): 7.50 (d, 1H,
C-4 H); 2.40 (s, 3H, -CH ₃ ):
ppm.

Elemental analysis as C ₆ H ₅ Cl ₂ N (molecular weight 162.02): Calculated values C44.48% H3.11% N8.65% Cl43.77% Actual values C44.4% H2.9% N7.9% Cl53. 8%.

Example 1 a) Production of 2,2-dichloro-3,3,3-trifluoropropionaldehyde 4,4-dichloro-5,5,5 trifluoro-2-methyl-2-pentenecarboxylic acid methyl ester (100.4 g ) in glacial acetic acid (800 ml) at 20° C. 19.2 g of ozone (mixture with oxygen) was introduced. Next, a suspension of zinc powder (15 g) in water (15 ml) was added and distilled, and the produced 2,2-dichloro-3,3,3-trifluoropropionaldehyde was distilled under normal pressure. 52.8 g of product was obtained as a colorless pungent liquid.

Boiling point: 66-67℃.

IR( _CCl4 ): ν(CO)1770cm ^-1 .

^1H -NMR-spectrum (CDCl ₃ ): δ=9.3
(q, J=2Hz) ppm.

Elemental analysis as C ₃ HCl ₂ F ₃ O (molecular weight 180.9): Calculated values C19.92% H0.56% N31.50% CI39.9% Actual values C20.2% H0.8% N30.9% Cl38. Five %.

b) 4-formyl-2,4-dichlor-5,
Production of 5,5-trifluorovaleronitrile 2,2-dichloro-3,3,3-trifluoropropionaldehyde 36g, acetonitrile
80 ml of acrylonitrile and 0.5 g of copper() chloride were heated in a tantalum autoclave for 12 hours. Work-up according to Example 1a) gave 4-formyl-2,4-dichloro-5,5,5-trifluorovaleronitrile as a colorless oil.

Boiling point: 85-86℃/900pa.

IR (CCl ₄ ): ν(CN) 550cm ^-1 , ν(CO) 1750cm
^{-1 1} H—NMR—spectrum (CDCl ₃ ): δ=9.56
(m, 1H, CHO); 4.7 (m, 1H, C-2-
3); 2.7-3.3 (m, 2H, C-3H) ppm (diastereomer mixture).

Elemental analysis as C ₆ H ₄ Cl ₂ F ₃ NO (molecular weight 234.0): Calculated values C30.80% H1.73% N5.99% Cl24.36% Actual values C31.5% H2.0% N5.9% Cl23.8%.

c) Production of 2,3-dichloro-5-trifluoromethylpyridine 4-formyl-2,4 obtained from Example 1b)
-Dichloro-5,5,5-trifluoroveronitrile (25.0 g) was heated with 0.1 g of copper powder at 170° C. for 5 hours in a tantalum autoclave. Steam distillation yielded 11.9 g of 2,3-dichloro-5-trifluoromethylpyridine as a colorless oil with a peppery odor.

Boiling point: 80℃/3325pa.

^1H -NMR-spectrum (CDCl ₃ ): δ=8.63
(d, J=2Hz, 1H): 8.03 (d, J=2Hz,
1H) ppm.

Elemental analysis calculated value as C ₆ H ₂ Cl ₂ F ₃ N (molecular weight 216.0) C33.36% H 0.93% N6.46% Cl32.82% F26.28% Actual value C33.5% H 1.0% N6.5 % Cl33.4% F25.9%

Claims (1)

[Claims] 1. 2.2-dichloro-3,3,3-trifluoropropionaldehyde. 2 4,4-Dichloro-5,5,5-trifluoro-2-methyl-2-pentenecarboxylic acid is subjected to ozonolysis and then an aqueous suspension of zinc dust is added to the reaction mixture to give 2,2- Dichlor-3,3,3
-2,2-dichloro-3,3,3 characterized by distilling trifluoropropionaldehyde
-Production method of trifluoropropionaldehyde.