HU185165B - Process for preparing 6-/substituted phenoxy/-piolinaldehyde derivatives - Google Patents

Abstract

Compounds are prepared corresponding to the formula (FORMULA) wherein Y represents chloro or R'; R represents (FORMULA) wherein X independently represents alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, alkyl sulfonyl of 1 to 4 carbon atoms, trifluoromethyl, chloro, fluoro or bromo; n represents an integer of 0 to 2 or X<un>u represents 3, 4-methylenedioxy and R' represents R with the proviso that R and R' can be the same or different. The compounds are useful as intermediates for the preparation of insecticidal substituted pyridine methyl esters of cyclopropane carboxylic acids.

Description

Substituted phenoxypyridine methyl esters of cyclopropane carboxylic acids are known from U.S. Patent 4,163,787, issued August 7, 1979. The above compounds are useful for controlling various insect pests. They were prepared according to the above patent by reacting a suitable substituted phenoxypyridine methanol with the appropriate 2,2-dimethyl-3- (2,2-dihaloethenyl) cyclopropanecarbonyl halide.

Although the above process afforded the desired compounds in sufficient yield, the high cost of substituted phenoxy-pyridine methanols required by the process rendered the process so expensive that it was not economical to produce the desired compounds on a commercial scale.

Substituted phenoxypyridine methanols are prepared from the corresponding picolonaldehydes, whereas the latter compounds are obtained from the corresponding methyl picolinate. Due to the high price of the above aldehyde and picolinate intermediates, the price of substituted phenoxypyridine methanol is also high. Therefore, we have been looking for new, cheaper methods for producing the above materials.

The present invention relates to a process for the preparation of 6- (substituted phenoxy) picolinaldchide derivatives of the general formula (X). In the general formula (X)

R 'is a group of formula II in the latter formula

X is independently C 1-4 alkyl, C 1-4 alkylthio, C 1-4 alkylsulfonyl, chlorine, fluorine or bromine, and n is 0 or 1, or

X _{n represents a} 3,4-methylenedioxy group.

According to the process of the present invention, compounds of formula (X) are prepared from novel starting compounds of formula (1). In the general formula (I)

Y is chlorine or R ', and

R ^r and R is the same or different, is a group (II), wherein

X and n are as defined in formula (X).

According to the present invention, compounds of formula (X) are prepared by reacting a compound of formula (I) wherein Y is R 'and R and R' are as defined above with an organic or inorganic acid, optionally a solvent. in the presence of 60-150 ° C.

The picolinaldehydes obtained by the process of the invention can be converted into substituted phenoxypyridine methanols. The latter compounds are then reacted with the corresponding 2,2-dimethyl-3- (2,2-dihaloethenyl) -cyclopropanecarbonyl halide to give the insecticidal cyclopropanecarboxylic acid (substituted) according to U.S. Patent 4,163,787. pyridine) methyl esters.

The novel starting materials of formula (I) according to the invention are either solids or liquids, slightly soluble in water, and moderately soluble in common organic solvents.

The starting materials of formula (I) according to the invention are prepared by reacting 1 mole of 6-chloro-2-dichloromethylpyridine with 1-3 moles of at least one type of alkali metal phenolate of formula (IV) in the presence of a solvent. .

A group of compounds of formula I are those compounds wherein R 'and R 5 are the same. Those compounds of formula ₍₁₎ is prepared by reacting one mole of 6-chloro-2- (dichloromethyl) pyridine [formula (III)] is substituted with 3 moles of an alkali metal phenolate in accordance [Formula (IV)] is reacted with a in the presence of a solvent. The progress of the reaction up to Scheme 1 is shown. In formula (IV), X and n are as defined above and M is sodium, potassium, lithium or cesium.

The reaction is carried out by mixing the reagents with a solvent and stirring for 2 to 24 hours at 100 to 200 ° C. The reaction mixture is cooled, diluted with water and extracted with a solvent such as 1,1,1-trichloroethane, methylene chloride, chloroform, ethyl acetate or ethyl ether. The organic extract is washed with water, dried and concentrated under reduced pressure and, if desired, purified by distillation or other conventional methods.

In the reaction, the reagents are consumed in stoichiometric proportions, that is, 1 molar equivalent of the pyridine reagent is reacted with 3 molar equivalents of the phenol reagent.

However, due to the nature of the reaction, it is preferable to use an excess of 5-25% phenol reagent.

In the above process, the phenol reagent is used in the form of the finished alkali phenolate. However, the alkali metal salt of phenol can also be prepared in situ. In this case, the pyridine reagent is mixed with an appropriately substituted methoxyphenol and an alkali metal hydroxide in a solvent and then heated to the reaction mixture as described above. An equivalent amount of alkali metal hydroxide is added to the reaction mixture using the phenol reagent used.

Dimethylsulfoxide, dimethylformamide, N-methyl-2-pyrrolidone, toluene or xylene may be used as solvents in the above reactions.

Another group of compounds of formula (I) comprises 40 compounds of formula (I) wherein Y is chloro. Compounds of formula (Ig) are prepared by reacting 1 mole of 6-chloro-2- (dichloromethyl) pyridine (III) with 2 moles of appropriately substituted alkali metal phenolate (IV) in a suitable solvent. The progress of the reaction is illustrated in Scheme 2. Selection and recovery of the desired product identical módpn Reaction conditions occurs than for the preparation of compounds of formula _(1).

A third group of compounds of formula (I) are those compounds of formula (I) wherein R and R * are different. The compounds of formula (1) can be prepared by the addition of 1 mole of 6-chloro-2- [di (substituted phenoxy) methyl] pyridine (1g) prepared as above to 1 mole of a differently substituted alkali metal. with phenolate in a solvent. The reaction scheme is illustrated in Scheme 3. The reaction conditions and separating the desired product was identical to that described for előzőek60 (I _A) and (Ig) Compounds of formula.

The resulting 6- (substituted phenoxy) -2- [di (substituted phenoxy) methyl] pyridines are hydrolyzed under acidic hydrolysis with an organic or inorganic acid, optionally in the presence of a solvent (X).

_1,185,163 -2-f _2. Table: Compounds of formula (U) prepared in Example 2

calculated H% ANALYSIS found Physical characteristics N% % C % C H% N% 78.03 5.18 3.79 77.96 5.03 3.83 op. = 85-86.5 ° C 3-Cl np = 1.6728 4-Br 47,52 2.64 2.33 47.04 2.71 2.22 op. = 114-136 ° C 4-CH ₃ 78.83 6.98 3.41 78.17 6.11 3.30 ηθ = 1.5955 3-CF ₃ 56.54 2.79 2.44 56.22 2.81 2.39 Πρ = 1.5096 3-F 68.09 3.78 3.31 67.84 3.88 3.22 Πρ = 1.5717

Πρ - refractive index op. = melting point

2o

Example 3 Preparation of Old (3-fluorophenoxy) picolinaldehyde (Formula VII)

2.5 g (0.0059 mol) of 2- [bis (3-fluorophenoxy) methyl] -6- (3-fluorophenoxy) pyridine are dissolved in 20 ml of 80% acetic acid. The solution was heated at 150 ° C overnight with stirring. The reaction mixture was cooled, diluted with water and extracted with methylene chloride. The extract was washed with water and concentrated under reduced pressure. The desired product has a melting point of 42-43 ° C.

Example 4

6-Phenoxy-picolinaldehyde [Formula VIII]

Dissolve 0.5 g of 2- [bis (phenoxy) methyl] -? - phenoxypyridine in 15 ml of 3,4-dioxane. To the solution was added 5% sulfuric acid dropwise until the solution became turbid. The solution was heated on a steam bath at 80-90 ° C for about 10 minutes and the reaction mixture was poured into water (20 mL). A yellowish emulsion is obtained which is extracted with 50 ml of ethyl ether. The extract was washed with 50 ml of 5% aqueous sodium hydroxide solution, three times with 50 ml of water, and finally with 50 ml of water.

III. Preparation of Compounds of Formula IX

ANALYSIS

Xn calculated found M.p. % C H% N% % C H% N% 3-F 66.3h 3.71 6.45 66.32 3.92 6.21 42-43 4-F 66.36 3.71 6.45 66.0? 3.95 6.45 38-39 4-Br 51.82 2.90 5.04 51.4 3.02 4.89 61-63 3-Cl 61.68 3.45 6.00 61.62 3.56 5.85 58-59 4-C1 61.68 3.45 6.00 61.22 3.58 5.81 45-46 4-CH ₃ 73.22 5.20 6.57 73.1 0 5.30 6.56 42-43 3-CH ₃ 73.22 5.20 6.57 72.82 5.35 6.51 36-37 4-SCH ₃ 63.65 4.52 5.71 63.1 1 4.60 5.70 62-63 4-SO ₂ CH ₃ 135-136 3,4-O-CH ₂ -O 88-89

185 to the corresponding 6 (substituted phenoxy) picolinaldehydes.

During the above hydrolysis, 1 mol of 6- (substituted phenoxy) 2- [di (substituted phenoxy) methyl] pyridine is mixed with an excess of organic or inorganic acid such as sulfuric acid, dilute hydrochloric acid or acetic acid. The reaction may be carried out, if desired, in a solvent in a cut reaction medium such as 1,4-dioxane, ethylene glycol monomethyl ether or water. The reaction mixture is heated to 60-150 ° C for 10 minutes to 12 hours or more. The reaction mixture is cooled, diluted with water and extracted with a solvent such as ethyl ether, methylene chloride or chloroform. The desired product is recovered from the solvent extract by conventional means, for example, after washing and drying with water, dilute sodium hydroxide solution and saturated brine, the solvent is distilled off under reduced pressure.

The following examples are intended to illustrate the process of the invention.

Example 1

Preparation of 6-chloro-2- (diphenoxymethyl) pyridine (Formula V) 25 g (0.13 mol) of 6-chloro-2- (dichloromethyl) pyridine, 29.21 g (0.32 g). mole) of phenol, 17.48 g (0.32 mole) of potassium hydroxide and 100 ml of dimethylsulfoxide was heated at 70 ° C with stirring for 6 hours. The reaction mixture was cooled, diluted with water and extracted with 1,1,1-trichloroethane. The extract was washed with water, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. Fractional distillation of the residue gave 27.3 g of a yellow viscous liquid whose chemical structure was confirmed by NMR spectroscopy and elemental analysis. The product has a boiling point of 150 DEG C. at 12.9 Pa and a refractive index of n _D = 1.5991.

Elemental analysis results:

H, 4.49; N, 4.49. Found: C, 68.63; H, 4.40; N, 4.49.

The compounds of Table I can also be prepared as described above.

In a similar manner to the above procedure, about 1 mole of the appropriately substituted phenol and 1 mole of 6-chloro-2- [difsubstituted phenoxy) methyl] pyridine was reacted to afford the title compound. The compounds of Table II can be prepared.

Example 2

Preparation of - [bis (4-methoxy-phenoxy) -methyl] -6- (4-methoxy-phenoxy) -pyridine [Formula VI]

15.04 g (0.076 mol) of 2- (dichloromethyl) -6-chloropyridine, 39.50 g (0.32 mol) of para-methoxyphenol, 18.14 g (0.32 mol) of potassium hydroxide and A mixture of dimethyl sulfoxide (100 mL) was heated with stirring for 72 h. The resulting mixture was cooled to 25 ° C, diluted with water and extracted with 1,1,1-trichloroethane. The extract was washed with water, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue is fractionally distilled to remove impurities with a boiling point below 200 DEG C. at a pressure of 6.45 bar. The desired product is a brown, dense oil. Yield: 25.3 g.

Elemental analysis results:

date; C, 70.59; H, 5.45; N, 3.05; Found: C, 70.80; H, 5.37; N, 3.09.

Prepared in the same manner as in Example II. Table I also provides compounds.

Table I: Compounds of formula (Ig) prepared according to Example 1

x _n calculated Analysis found Physical characteristics % C H% N% % C H% N% 4-C1 56.77 3.15 3.68 56.44 3.14 3.72 η ”= 1.6063 3-OCH3 64.60 4.85 3.77 64.28 4.98 3.47 Πρ = 1.5920 4-Br 46.01 2.56 2.98 45.31 2.63 2.85 op. = 75-78 ° C 4-CH3 70.69 5.30 4.12 69.95 5.35 4.07 Πρ = 1.5850 3-CF3 53.63 2.68 3.13 53.41 2.73 3.17 n "= 1.5146 3-F 62.16 3.45 4.03 62.45 3.62 4.03 Πρ = 1.5720 4-F 62.16 3.45 4.03 61.93 3.54 4.07 ηθ = 1.5705 4-OCH ₃ 64.60 4.85 3.77 64.38 4.99 3.56 Πρ = 1.5910

ηθ = refractive index op. = melting point

-4185 165 solution of saturated sodium chloride! washed. The extract was dried over anhydrous sodium sulfate and the solvent was distilled off under reduced pressure. The residual yellow-orange oil, which solidifies partially on cooling, yields 0.25 g of the desired product. The structure was confirmed by infrared and NMR spectroscopy.

The compounds of formula IX listed in Table III are also prepared according to the above procedure.

6-Chloro-2- (dichloroethyl) -pyridine is a known compound for use in the preparation of starting materials and may be prepared as described in U.S. Patent No. 3,687,827.

Claims (7)

A process for the preparation of 6- (substituted phenoxy) -picelinaldehyde derivatives of the formula (X): R * is a group of formula II in the latter formula X is independently C 1-4 alkyl, C 1-4 alkylthio, C 1-4 alkylsulfonyl, chloro, bromo or fluoro, n is 0 or 1, or X _{n represents a} 3,4-methylenedioxy group, characterized in that a compound of formula (I) in which YR 'represents and R' and R have the same or different meanings is inorganic or organic acid, if desired, hydrolyzed in the presence of a solvent at 60-350 ° C. 2. The i. A process for the preparation of 6-phenoxy-picolinaldehyde according to claim 1, wherein the 6-phenoxy-2-diphenoxymethyl-pyridine is hydrolyzed. 3. It!. A process for the preparation of 6- (4-methyl-3-phenoxy) -picolinaldelide according to claim 1, wherein 6- (4-phenoxy) -2- [bis (4-menophenoxy) nethyl] pyridine is hydrolyzed. The process of claim 1 for the preparation of 6- (3-chlorophenoxy-picolmaldehyde), characterized in that he (3-chlorophenoxy) -2- {bis (3-chlorophenoxy) does not prohibit -pyridine nt hi drolysis. 5. A process according to claim 1 for the preparation of 6- (4-chlorophenoxy) -picolinyldehyde, which is hydrolyzed by 6- (4-chlorophenoxy) -2- [bis (4-chlorophenoxy) nictyl] pyridine. . 6. A process for the preparation of 6- (3-fluorophenoxy) picolinaldehyde according to claim 3, characterized in that 6- (3-fluorophenoxy) -2- [bis (3-fluorenoxy) methyl] -pyridine is hydrolyzed. 7. A process for the preparation of 6- (4-phenoxy) -picolinaldehyde according to claim 1, wherein 6- (4-fluorophenoxy) -2- [bis (4-fluoro-phenoxy) methyl] is obtained. ] -pyridine is hydrolyzed.