JPH07179435A - Production of phenoxymethylpyrimidine derivative - Google Patents

Abstract

PURPOSE:To enable the production of a phenoxymethylpyrimidine derivative which is useful as a herbicide by conversion of a specific phenoxyacetic acid into an acid halide followed by reaction of the acid halide with a specific dialkylpropanediimidate dihydrochloride. CONSTITUTION:A phenoxyacetic acid derivative of formula I (X is halogen, a lower alkyl, a lower alkoxy, a lower acyloxy, nitro; n is 0 to 2; A is H, a lower alkyl, a lower alkenyl, a lower alkynyl, a substituted lower alkyl, a substituted lower alkenyl, a substituted lower alkynyl) is allowed to react with an inorganic halide into an acid halide. Then, the acid halide is allowed to react with a dialkyl propanediimidate dihydrochloride to give a phenoxymethylpyrimidine derivative of formula III. It preferred that the reaction between the acid halide and the compound of formula II is carried out in the presence of a base such as potassium carbonate or sodium carbonate.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for producing a phenoxymethylpyrimidine derivative useful as a herbicide. More specifically, it relates to a method for producing a phenoxymethylpyrimidine derivative by converting various phenoxyacetic acid derivatives into acid halides and then reacting them with dialkylpropanediimidate dihydrochloride.

[0002]

2. Description of the Related Art Japanese Patent Application Laid-Open No. 4-327578 discloses the following general formula (IV):

[0003]

[Chemical 4]

[Wherein X represents a halogen atom, a lower alkyl group, a lower alkoxy group, a lower acyloxy group or a nitro group, n represents 0, 1 or 2, and Y represents a hydrogen atom, a lower alkyl group, a lower alkenyl. Group, a lower alkynyl group, a substituted lower alkyl group, a substituted lower alkenyl group, a substituted lower alkynyl group, an alkali metal atom, an alkaline earth metal atom or an ammonium cation which may be substituted with an alkyl group, R ¹ and R ² Each independently represent a lower alkyl group], and a herbicide containing the phenoxymethylpyrimidine derivative as an active ingredient. Further, as a production method for producing the compound represented by the general formula (IV), the following general formula (V)
A salicylic acid derivative represented by the following formula and a pyrimidine derivative represented by the following general formula (VI) are reacted in the temperature range of −78 ° C. to the boiling point of the solvent using a suitable base without solvent or in the presence of a suitable solvent. The manufacturing method is described.

[0005]

[Chemical 5] [In the formula, X, n, Y, R ¹ and R ² are each represented by the general formula (IV).
And Z is a halogen atom or an alkylsulfonyloxy group.]

[0006]

However, the above-mentioned production method has a drawback that it cannot be said to be an industrially advantageous method because it requires a relatively long process.
An object of the present invention is to provide a method for efficiently producing a phenoxymethylpyrimidine derivative, which requires a long process in the conventional method.

[0007]

Means for Solving the Problems As a result of earnest studies to efficiently obtain a phenoxymethylpyrimidine derivative, the present inventors have found that after converting a specific phenoxyacetic acid into an acid halide, a specific dialkylpropane imidate dihydrochloride is obtained. The present invention has been completed by finding that the above object can be achieved by reacting with a salt. That is, the present invention provides the following general formula (I):

[0008]

[Chemical 6]

[Wherein X represents a halogen atom, a lower alkyl group, a lower alkoxy group, a lower acyloxy group or a nitro group, n represents 0, 1 or 2, and A represents hydrogen, a lower alkyl group, a lower alkenyl group. , A lower alkynyl group,
A substituted lower alkyl group, a substituted lower alkenyl group or a substituted lower alkynyl group, and R represents a lower alkyl group]
In producing the phenoxymethylpyrimidine derivative represented by the following general formula (II):

[0010]

[Chemical 7]

A phenoxyacetic acid derivative represented by the formula [wherein X, n and A are as defined above] is reacted with an inorganic halide to convert into an acid halide, and then the following general formula (V):

[0012]

[Chemical 8]

The present invention provides a process for producing a phenoxymethylpyrimidine derivative, which comprises reacting with a dialkylpropane diimidate dihydrochloride represented by the formula [wherein R has the same meaning as defined above].

[0014]

DETAILED DESCRIPTION OF THE INVENTION The term "lower" as used herein means that the group or compound to which this term is attached has 6 or less carbon atoms, and particularly preferably 1 to 4. X, A and R in the above general formulas (I), (II) and (III)
Specific examples of the atoms and groups of and Q will be described below. Halogen atom : Fluorine, chlorine, bromine, iodine and the like can be mentioned. Lower alkyl group : for example, methyl, ethyl, normal propyl, isopropyl, normal butyl, sec-butyl,
Mention may be made of a linear or branched lower alkyl group having 1 to 6 carbon atoms such as tert-butyl, n-pentyl, neopentyl, tert-pentyl or hexyl group. Lower alkoxy group : For example, a lower alkoxy group containing the lower alkyl group as an alkyl moiety such as methoxy, ethoxy, propoxy, normal propoxy, isopropoxy, normal butoxy, secondary butoxy, tertiary butoxy or pentoxy group. You can

Lower acyloxy group : Examples include lower acyloxy groups having 2 to 7 carbon atoms such as acetoxy, propionyloxy, butyryloxy or isobutyryloxy groups. Lower alkenyl group : For example, a lower alkenyl group having 2 to 6 carbon atoms such as vinyl, allyl, 3-butenyl or 1-methyl-2-propenyl group can be mentioned. Lower alkynyl group : For example, a lower alkynyl group having 3 to 6 carbon atoms such as propargyl, 2-butynyl or 3-butynyl group can be mentioned. These exemplified atoms and groups can be selected arbitrarily or in combination according to common general knowledge. For example, the halogen atom represented by Q is a chlorine atom, and the lower alkyl group represented by R is Is particularly preferably methyl.

The phenoxyacetic acid derivative represented by the general formula (II) can be produced according to the method described in, for example, JP-A-63-258463 and JP-A-1-299223. In addition, the general formula (III)
The dialkylpropane diimidate dihydrochloride represented by can be synthesized, for example, according to the method described in Journal of American Chemical Society, Volume 71, page 40 (1949).

The conversion of the phenoxyacetic acid derivative represented by the general formula (II) into an acid halide is carried out by using a generally known inorganic halide such as phosphoryl chloride, thionyl chloride, phosphorus pentachloride, phosphorus trichloride or It can be easily performed by a method using phosgene or the like. Pyridine, triethylamine, hexamethylphosphoric triamide and the like can also be used with thionyl chloride. The above conversion can be carried out without solvent or in the presence of a suitable solvent, and the solvent used is not particularly limited as long as it is substantially inert to the reaction, for example, benzene, Aromatic hydrocarbon solvents such as toluene and xylene; halogenated hydrocarbon solvents such as methylene chloride and chloroform; dimethylformamide and the like. The pressure during this reaction is not particularly limited, but it is usually carried out under normal pressure. The reaction temperature is not particularly limited, but the reaction is carried out at a temperature ranging from room temperature to the boiling point of the reaction reagent or solvent [eg,
See Journal of American Chemical Society, 67, 408 (1945). ].

In the reaction of the next step, the acid halide obtained by the above reaction is in the range of 1 to 1.5 equivalents based on 1 of the dialkylpropane diimidate dihydrochloride represented by the general formula (III). Used. The acid halide can be reacted with the dialkylpropanediimidate dihydrochloride represented by the general formula (III) to obtain the desired phenoxymethylpyrimidine derivative. This reaction is preferably carried out in the presence of a base, and examples of the base used at that time include triethylamine,
Examples thereof include organic bases such as diisopropylethylamine; and carbonates such as sodium carbonate, sodium hydrogencarbonate, potassium carbonate, potassium hydrogencarbonate, and the like. Among them, potassium carbonate and sodium carbonate are preferable. The amount of the base used is appropriately in the range of 3 to 5 equivalents with respect to the compound 1 represented by the general formula (III).

The solvent used in the present invention is
There is no particular limitation as long as it is substantially inert to the above reaction, and examples thereof include halogenated hydrocarbon solvents such as methylene chloride and chloroform; aromatic hydrocarbon solvents such as benzene, toluene and xylene; diethyl ether. , Tetrahydrofuran, ether solvents such as 1,4-dioxane, etc .;
Ketone-based solvents such as acetone and methyl ethyl ketone; ester-based solvents such as methyl acetate, ethyl acetate and butyl acetate;
Examples thereof include acetonitrile and a mixed solvent of the above-mentioned organic solvent and water. As a preferable solvent, a mixed solvent of an organic solvent and water can be mentioned, and in particular, a combination of methylene chloride and water, toluene and water, ethyl acetate and water and the like are preferable. Any mixing ratio can be selected as the mixing ratio of the mixed solvent, but preferably water / organic solvent = 10/1.
~ 1/10, particularly preferably water / organic solvent = 2/1 to 1
/ 5. The amount of solvent is not particularly limited, but 1 to 100 ml per 1 g of the compound represented by the general formula (IV).
It is preferable to use the above range.

The pressure during this reaction is not particularly limited,
Usually, it is performed under normal pressure. The reaction temperature is not particularly limited, but the reaction is carried out at a temperature in the range of -78 to 100 ° C.
According to the method of the present invention, the phenoxymethylpyrimidine derivative, which is the target compound, can be obtained in a reaction time of 1 to 24 hours, depending on the reagents used and the set conditions such as reaction temperature.

After the completion of the reaction, the reaction product is extracted with an organic solvent, and the concentrated residue of the extracted organic layer is purified by a method such as recrystallization or silica gel column chromatography to obtain the objective compound phenoxymethylpyrimidine. The derivative can be isolated. The present invention will be described in more detail with reference to examples below, but the present invention is not limited to these examples.

[0022]

EXAMPLES Example 1: 2'-methoxycarbonyl-3'-chlorophenyl
Synthesis of enoxyacetic acid Sodium hydride (60% oil suspension) 1.
A suspension of 11 g and 50 ml of dimethylformamide-
Cool to 5 ° C. and add 6-chlorosalicylic acid to this suspension 4.
A solution prepared by dissolving 5 g in 10 ml of dimethylformamide was added dropwise. After stirring the reaction solution at 0 ° C. for 20 minutes,
3.37 g of sodium chloroacetate was added. After raising the temperature to room temperature, the mixture was stirred at 60 to 70 ° C. for 3 days. After cooling, the liquid was poured into water and extracted with ethyl acetate.
The organic layer was extracted with saturated aqueous sodium hydrogen carbonate, the aqueous layer was acidified with concentrated hydrochloric acid and then extracted with ethyl acetate. The organic layer was dried using magnesium sulfate, ethyl acetate was distilled off under reduced pressure,
4.27 g (yield 74%) of the title compound was obtained. [1-NMR (δ, CDCl ₃ ); ppm: 3.98 (3H,
s) 4.73 (2H, s) 6.80 (1H, d) 7.10 (1H, d) 7.30 (1
H, dd) 8.57 (1H, br)] Melting point: 118-120.5 ° C

Example 2: Methyl 2-chloro-6-
Synthesis of (chloroformyl) methyloxybenzoate 0.8 ′ of 2′-methoxycarbonyl-3′-chlorophenoxyacetic acid synthesized in the same manner as in Example 1 above was stirred with 10 ml of thionyl chloride under reflux for 1 hour.
After cooling, excess thionyl chloride was distilled off under reduced pressure, and the solution was azeotropically distilled with toluene. Obtained oily substance 0.8
6 g was subjected to the following reaction without further purification.

Example 3: Methyl 6-chloro-2-
{(4,6-dimethoxy-2-pyrimidyl) methyloxy
Synthesis of Ci} Benzoate A suspension of 0.8 g of dimethylpropanediimidate dihydrochloride in 6 ml of methylene chloride was cooled to -40 ° C, and a solution of 1.48 g of diisopropylethylamine in 2 ml of methylene chloride was added dropwise. did. -40 to -3
After stirring at 0 ° C. for 15 minutes, 0.86 g of a crude product of methyl 2-chloro-6- (chloroformyl) methyloxybenzoate synthesized by the same method as in Example 2 was dissolved in 4 ml of methylene chloride. Was added dropwise at -40 ° C. The obtained solution was stirred at -40 to -30 ° C for 1 hour, then at room temperature for 4 hours, and then water under ice cooling.
10 ml was added. The organic layer was separated, washed with saturated aqueous sodium hydrogen carbonate and saturated brine, and dried over sodium sulfate. Methylene chloride was distilled off under reduced pressure, and the obtained concentrated residue was purified by silica gel chromatography to obtain 0.34 g (yield 31%) of the title compound. [1-NMR (δ, CDCl ₃ ); ppm: 3.87 (6H,
s) 3.95 (3H, s) 5.16 (2H, s) 5.91 (1H, s) 6.84 (1
H, d) 6.98 (1H, d) 7.20 (1H, dd)] Melting point: 124 to 126 ° C

Example 4: Methyl 6-chloro-2-
{(4,6-dimethoxy-2-pyrimidyl) methyloxy
Synthesis of Ci} Benzoate 0.8 g of dimethylpropanediimidate dihydrochloride and 1.75 g of potassium carbonate were cooled to -40 ° C, and 11.4 ml of methylene chloride was added. After stirring at -40 to -30 ° C for 15 minutes, 0.86 g of a crude product of methyl 2-chloro-6- (chloroformyl) methyloxybenzoate synthesized by the same method as in Example 2 was added to methylene chloride 1.
The solution dissolved in 0 ml was added dropwise at -40 ° C. After stirring this at -40 to -30 degreeC for 1 hour, it stirred at room temperature for 4 hours, and then 10 ml of water was added under ice cooling. The organic layer was separated, washed with saturated aqueous sodium hydrogen carbonate and saturated brine, and dried over sodium sulfate. The title compound was obtained by distilling off methylene chloride under reduced pressure and purifying the resulting concentrated residue by silica gel chromatography.
0.30 g (yield 27%) was obtained. [1-NMR (δ, CDCl ₃ ); ppm: 3.87 (6H,
s) 3.95 (3H, s) 5.16 (2H, s) 5.91 (1H, s) 6.84 (1
H, d) 6.98 (1H, d) 7.20 (1H, dd)] Melting point: 124 to 126 ° C

Example 5: Methyl 6-chloro-2-
{(4,6-dimethoxy-2-pyrimidyl) methyloxy
Synthesis of Ci } benzoate 1.79 g of potassium carbonate was dissolved in 3.4 ml of water, and 6.8 ml of methylene chloride was added to this solution. This solution was cooled to 0 ° C., 0.68 g of dimethylpropanediimidate dihydrochloride was added, and the mixture was stirred at 0 ° C. for 15 minutes. 0.88 g of a crude product of methyl 2-chloro-6- (chloroformyl) methyloxybenzoate synthesized by the same method as in Example 2 was added to this solution.
The solution dissolved in ml was added dropwise at 0 ° C. The resulting solution was stirred at 0 ° C. for 4 hours, then 10 ml of water was added. The organic layer of the liquid was separated, washed with saturated saline, and then dried with sodium sulfate. Methylene chloride was distilled off under reduced pressure, and the obtained concentrated residue was purified by silica gel chromatography to give the title compound 0.9.
0 g (yield 79%) was obtained. [1-NMR (δ, CDCl ₃ ); ppm: 3.87 (6H,
s) 3.95 (3H, s) 5.16 (2H, s) 5.91 (1H, s) 6.84 (1
H, d) 6.98 (1H, d) 7.20 (1H, dd)] Melting point: 124 to 126 ° C

Example 6: Tertiary butyl 6-ku
Lolo-2-{(4,6-dimethoxy-2-pyrimidyl)
Synthesis of methyloxy} benzoate 1.32 g of potassium carbonate was dissolved in 3.4 ml of water, and 6.8 ml of methylene chloride was added to this solution. The solution was cooled to 0 ° C. and dimethyl propane diimidate dihydrochloride was added.
After adding 50 g, the mixture was stirred at 0 ° C. for 15 minutes. A solution prepared by dissolving 0.80 g of a crude product of tert-butyl 2-chloro-6- (chloroformyl) methyloxybenzoate synthesized in the same manner as in Example 2 in 7 ml of methylene chloride was added to this solution at -5. It was added dropwise at -2 ° C. The resulting solution was stirred at −4 to 0 ° C. for 4 hours, then 10 ml of water was added. The organic layer of the liquid was separated, washed with saturated saline, and then dried with sodium sulfate. Methylene chloride was distilled off under reduced pressure, and the obtained concentrated residue was purified by silica gel chromatography to obtain 0.60 g (yield 64%) of the title compound. [ ¹ H-NMR (δ, CDCl ₃ ); ppm: 1.57 (9 H,
s), 3.87 (6H, s), 5.13 (2H, s), 5.92 (1
H, s), 6.83 (1H, d), 6.95 (1H, d), 7.1
5 (1H, dd) melting point: 116.8-118 ° C]

Example 7: 6-chloro-2-{(4,6
-Dimethoxy-2-pyrimidyl) methyloxy} benzo
Synthesis of ic acid 2.13 g of potassium carbonate was dissolved in 3.4 ml of water, and 6.8 ml of methylene chloride was added to this solution. Solution at 0 ℃
Cool to dimethyl propanediimidate dihydrochloride.
After adding 64 g, 0.73 g of 2'-carboxy-3'-chlorophenoxyacetic acid was added to 10 m of thionyl chloride.
After refluxing with 1, for 1.5 hours, excess thionyl chloride was distilled off, and a solution of the residue in 5 ml of methylene chloride was added dropwise at -6 to -2 ° C. The obtained solution is -6 to
Stir at 0 ° C. for 4 hours, then add 10 ml of water. The organic layer of the liquid was separated, washed with saturated saline, and then dried with sodium sulfate. Methylene chloride was distilled off under reduced pressure, and the obtained concentrated residue was purified by silica gel chromatography to give 0.37 g of the title compound.
(Yield 36%) was obtained. [ ¹ H-NMR (δ, CDCl ₃ ); ppm: 3.90 (6 H,
s), 5.35 (2H, s), 5.91 (1H, s), 6.97 (1
H, dd), 7.00 (1H, dd), 7.25 (1H, dd) Melting point: 165 to 167 ° C]

[0029]

INDUSTRIAL APPLICABILITY By the method of the present invention, a phenoxymethylpyrimidine derivative useful as a herbicide can be efficiently produced.

Claims (1)

[Claims] 1. The following general formula (I): [In the formula, X represents a halogen atom, a lower alkyl group, a lower alkoxy group, a lower acyloxy group or a nitro group,
n represents 0, 1 or 2, A represents hydrogen, a lower alkyl group, a lower alkenyl group, a lower alkynyl group, a substituted lower alkyl group, a substituted lower alkenyl group or a substituted lower alkynyl group, and R represents a lower alkyl group. ] In producing the phenoxymethylpyrimidine derivative represented by the following general formula (II): A phenoxyacetic acid derivative represented by the formula [wherein X, n and A have the same meanings as defined above] is reacted with an inorganic halide to convert into an acid halide, and then the following general formula (V): ] A method for producing a phenoxymethylpyrimidine derivative, which comprises reacting with a dialkylpropane diimidate dihydrochloride represented by the formula [wherein R has the same meaning as defined above].