JPH0524901B2 - - Google Patents

Description

[Detailed description of the invention]

[Industrial Application Field] The present invention relates to a novel pyrimidine derivative useful as a herbicide and a method for producing the same. [Prior Art] Chemical abstract compounds (Chem.
Abstr.) Volume 72, 55401y, Vol. 76, 148745m. However, the usefulness of these compounds for agricultural purposes has not been clarified at all. [Problems to be Solved by the Invention] While conducting research on pyrimidine derivatives, the present inventors discovered that the piperazinylpyrimidine compound of the present invention, which is different from that described in the preceding sentence, has novel and excellent herbicidal activity. This discovery led to the completion of the present invention. [Means for solving the invention] [Summary of the invention] The present invention is based on the general formula [] [In the formula, R ¹ is hydrogen, a phenyl group-substituted methyl group, or a benzyloxycarbonyl group which may be nuclear-substituted with a group selected from the group of halogen, alkoxy group and nitro group, and R ² is -
NR ⁵ R ⁶ (R ⁵ and R ⁶ are each hydrogen or a lower alkyl group), -OR ⁷ (R ⁷ is a lower alkyl group) or -SR ⁸ (R ⁸ is a lower alkyl group). )
and R ³ and R ⁴ are hydrogen or lower alkyl groups. Same below. The present invention relates to a novel pyrimidine derivative represented by: [Description of the substance of the present invention] The substance of the present invention is represented by the above general formula []. In the formula, the phenyl group-substituted methyl group of R ₁ is,
It shows a benzyl group, a diphenylmethyl group, and a triphenylmethyl group, and among them, a benzyl group is preferable.
In addition, R ⁵ to R ^{8 in each formula represented by R 2 and} lower alkyl of R ³ and R ⁴ in the formula [] are as follows:
Examples include methyl group, ethyl group, propyl group, isopropyl group, n-butyl group, isobutyl group, sce-butyl group, and tert-butyl group, among which methyl group, ethyl group, and isopropyl group are preferred. Specific examples of these compounds are shown in Table 1.

【table】

【table】

【table】

〔Production method〕

Each substance of the present invention can be manufactured through the following steps. Hereinafter, a case where R ¹ is a benzyl group will be explained as an example. (1st stage) This reaction is usually carried out by dissolving sodium hydroxide or potassium hydroxide in an alcohol such as ethanol, methanol, or propyl alcohol, preferably ethanol, adding the compound to the solution, and then gradually adding the compound in an equimolar amount to the solution. and react while stirring. In this case, the reaction is usually carried out at a temperature of 0 to 100°C for 4 to 8 hours.
In this case, it is preferable that the amount of sodium hydroxide used is equimolar to that of the compound. When using methanol etc., some -
Instead of COOC ₂ H ₅ , −COOCH ₃ etc. are obtained, but
It can be used as is in the next step. (Second stage) The reaction is carried out in a solvent volume of SOCl ₂ by heating the compound for 6 to 12 hours, preferably 8 to 10 hours while refluxing the SCCl ₂ . (Third stage) If R ² −NR ⁵ R ⁶ in formula [] (−
NH ² ) is a compound and an amine R ⁵ R ⁶ NH of 1 to 10 times the mole, preferably 4 times the mole of the compound, at a temperature of 0 to 50°C.
The compound can be obtained by reacting for 4 to 4 hours, preferably about 2 hours. In this case, the reaction solvent is preferably
In addition to CHCl ₃ , CH ₂ Cl ₂ , CH ₂ ClCH ₂ Cl, etc. can be used, and the amines R ⁵ R ⁶ NH may be added as they are or as an aqueous or alcoholic solution. Similarly, when R ² in formula [] is -OR ⁷ , it is 1 to 4 times the mole of the compound, preferably
1.25 times the mole of sodium alkoxide NaOR ⁷ was reacted with alcohol R ⁷ OH at 20 to 50°C.
Preferably at 25 to 35°C for 10 minutes to 2 hours,
Preferably, the reaction is allowed to proceed for about 1 hour. Furthermore, if R ² in formula [] is −SR ⁸ ,
Similarly, about twice the mole of each of R ⁸ SH and NaOR ⁸ dissolved in alcohol R ⁸ OH is allowed to act on the compound. In this case, the compound is chloroform,
It can be used dissolved in an alcohol such as R ⁸ OH or a solvent such as ethyl acetate. (Fourth step) The compound obtained above is hydrolyzed to obtain a compound. This reaction is H ₂ O−C ₂ H ₅ OH (H ₂ O/C ₂ H ₅ OH=
1/4) This can be carried out in a mixed solvent or by the usual method of reacting KOH in an equimolar amount or more, preferably about twice the molar amount. (Fifth Step) The substance of the present invention can be produced from a compound by the following reaction. In this reaction, as a first step, 1 to 3 times the mole, preferably 2 times the mole of SOCl ₂ is added to the compound.
and about 1 times the molar amount of Et ₃ N. Then, as a subsequent step, amines R ³ R ⁴ NH are allowed to act on the compound in an amount of 1 to 10 times the mole, preferably 6 to 7 times the mole. Benzene, ethyl acetate, CHCl ₃ , CH ₂ Cl ₂ ,
Using CH ₂ ClCH ₂ Cl, preferably CHCl ₃ , the reaction is carried out at a temperature of 10 to 50° C., preferably room temperature, for 10 minutes to 2 hours, preferably about 1 hour. The substance of the present invention in which R ¹ is a phenyl-substituted methyl group other than a benzyl group can also be produced in the same manner as described above. (Sixth Step) The substance of the present invention in which R ¹ is hydrogen can be produced by hydrogenolyzing a compound. Hydrocracking catalysts include Pd-carbon and Raney-carbon.
Ni, Pt-C, PdO, etc. can be used.
Reaction solvents are usually alcohols such as methanol, ethanol, and isopropanol, carboxylic acids such as formic acid, acetic acid, and propionic acid, esters such as ethyl acetate, ethanol-formic acid, or ethanol-
Using a mixed solvent such as acetic acid, at normal pressure to 10%
Kg/cm ² hydrogen is supplied, 0.1 to 10 hours at 10 to 100℃, preferably 40 to 80℃, 0.5 to 5
Allow time to react. (Seventh Step) The substance of the present invention in which R ¹ is a benzyloxycarbonyl group optionally substituted on the nucleus with a group selected from the group of halogen, alkoxy group and nitro group can be produced from a compound.
The following description will be made using a benzyloxycarbonyl group as an example where R ¹ is a benzyloxycarbonyl group, but it can be produced in the same way if it is a nuclear-substituted benzyloxycarbonyl group. In this reaction, C ₆ H ₅ CH ₂ OCOCl is 1 to 2 times the mole of the compound, preferably about 1.4
Two times the molar amount is used, and the reaction is carried out in THF at 30 to 60°C, preferably 45°C, for 4 to 24 hours, preferably about 12 hours. Although this reaction can be applied regardless of the type of R ² , it is particularly preferable to apply it to those in which R ² is -SR ⁸ . (Eighth Step) A compound in which R ¹ is hydrogen can also be produced by acid decomposing the above compound. In this case, it is preferable to use hydrochloric acid, hydrobromic acid, or the like as the acid, and to carry out the reaction in an acetic acid solvent. Usually, the reaction is carried out at a reaction temperature of 0 to 100°C for 0.5 to 10 hours. After the reaction, the compound can be obtained by neutralizing it with NaHCO ₃ or the like, and separating and purifying it by conventional methods. (Process for producing the substance of the present invention in which -NR ⁵ R ⁶ is -NH) The substance of the present invention in which -NR ⁵ R ⁶ of R ² in formula [] is -NH ₂ can be produced by the same reaction operation as in the first step. ,
It can be produced via the following reaction products. From the compound, -NR ⁵ R ⁶ is -
A substance of the invention that is NH ₂ can be produced. [Utility of the substance of the present invention] The substance of the present invention has excellent activity as a herbicide. That is, the substance of the present invention can be used as a herbicide for paddy fields and upland fields. The herbicides are particularly effective against paddy field weeds such as Japanese grasshopper, Japanese grasshopper, Japanese cypress, Japanese fireweed, and Japanese grasshopper, as well as upland weeds such as Japanese barnyard grass, Japanese grasshopper, Japanese grasshopper, and Japanese grasshopper. In order to use the substance of the present invention as a herbicide, the substance of the present invention can be used alone or in combination with carriers, surfactants, dispersants, adjuvants, etc., and formulated into wettable powders, emulsions, fine granules, granules, etc. It can be diluted to an appropriate concentration and sprayed, or applied directly. Hereinafter, the present invention will be specifically explained with reference to Examples, Test Examples, etc. Reference example 1 2-(4-benzylpiperazino)-4-hydroxypyrimidine-5-carboxylic acid ethyl ester 1 in an ethanol solution of 25.2 g of sodium hydroxide
-amidino-4-benzylpiperazine sulfate 160
g (0.60 mmol), and then 129.4 g (0.60 mmol) of diethyl ethoxy methylene malonate.
It was dripped in minutes. After refluxing for 5.5 hours, cool
The precipitated crystals were separated. The crystals were washed with water and then dried to obtain 131.4 g of the title compound (yield: 64%). Melting point 151-153℃ ^1H -NMR spectrum (CDCl ₃ solution, δppm) 1.36 (3H, t, J = 7Hz), 2.49 (4H, m),
3.54 (2H, s), 3.93 (4H, m), 4.35 (2H,
q, J=7Hz), 7.31 (5H, s), 8.63 (1H,
s) Reference example 2 2-(4-benzylpiperazino)-4-chloropyrimidine-5-carboxylic acid ethyl ester 2-(4-benzylpiperazino)-4-hydroxypyrimidine-5-carboxylic acid ethyl ester (compound synthesized in Reference Example 1) 130.0g (0.38mol)
A mixture of 390 ml and thionyl chloride was refluxed for 10 hours.
After adding 600 ml of toluene, the mixture was distilled to remove excess thionyl chloride. The mixture was cooled on ice, made alkaline by adding an aqueous sodium hydroxide solution, and extracted with chloroform. After drying the chloroform layer with _MgSO4 ,
By distilling off chloroform under reduced pressure, 120.2 g of the title compound was obtained as an oily product (yield: 88
%). ¹ H-NMR spectrum (CDCl ₃ solution, δppm) 1.36 (3H, t, J = 7Hz), 2.50 (4H, m),
3.56 (2H, br.s), 3.92 (4H, m), 4.32 (2H,
q, J = 7Hz), 7.35 (5H, s), 8.79 (1H,
s) Reference example 3 2-(4-benzylpiperazino)-4-ethylaminopyrimidine-5-carboxylic acid ethyl ester 72.3 g of 70% ethylamine aqueous solution ( 1.12 mol) was added dropwise over 15 minutes, and the mixture was stirred at room temperature for 2 hours. After adding water, extracting the oil with chloroform, and drying the chloroform layer with _MgSO4 ,
By distilling off chloroform under reduced pressure, 103.5 g of the title compound was obtained as an oily product (yield ~100
%) ¹ H-NMR spectrum (CDCl ₃ solution, δppm) 1.22 (3H, t, J = 7Hz), 1.32 (3H, t, J
=7Hz), (4H, m), 3.46 (2H, d, q, J
=5,7Hz), 3.54 (2H, s), 3.88 (4H,
m), 4.25 (2H, q, J = 7Hz), 7.31 (5H,
s), 8.00 (1H, br, t, J=5Hz), 8.58
(1H,s) The following compound was synthesized by a similar method. Structural formula R= _NHCH3 (mp71-74℃) R= ^NHPri R=N( _CH3 ) ₂ Reference example 4 2-(4-phenylpiperazino)-4-methoxypyrimidine-5-carboxylic acid methyl ester To a methanol solution (50 ml) of 1.88 g (34.8 mmol) of sodium methoxide was added 10.1 g of 2-(4-benzylpiperazino)-4-chloropyrimidine-5-carboxylic acid ethyl ester (compound synthesized in Reference Example 2) ( 28.0mmol) of methanol (40ml)
solution was added dropwise over 10 minutes. The mixture was stirred at room temperature for 1 hour, and methanol was distilled off under reduced pressure.
Water was added and extracted with chloroform. After drying the chloroform layer with MgSO ₄ , chloroform was distilled off under reduced pressure and the residue was recrystallized from methanol-ethyl acetate to obtain 7.9 g of the title compound (yield 79%) Melting point 135-138°C ¹ H-NMR spectrum (CDCl ₃ solution, δppm) 2.49 (4H, m), 3.54 (2H, s), 3.82 (3H,
s), 3.90 (4H, m), 3.97 (3H, s), 7.32
(5H, s), 8.71 (1H, s) Reference example 5 2-(4-benzylpiperazino)-4-methylthiopyrimidine-5-carboxylic acid ethyl ester A solution of 3 g (8.3 mmol) of 2-(4-benzylpiperazino)-4-chloropyrimidine-5-carboxylic acid ethyl ester (compound synthesized in Reference Example 2) in methylene chloride (10 ml) was prepared separately.
A solution of 1.16 g of CH ₃ SNa in methanol (3 ml) was added dropwise at room temperature, and the mixture was stirred for 2 hours. Then add water,
Extracted with methylene chloride. The methylene chloride layer was dried over anhydrous magnesium sulfate and then concentrated, and the residue was purified by column chromatography to obtain 1.16 g of the target product (yield 37%). ¹ H-NMR spectrum (CDCl ₃ solution, δppm) 1.35 (3H, t, J = 7Hz) 2.43 (3H, s),
2.51 (4H, m), 3.56 (2H, s), 3.95 (4H,
m), 4.32 (2H, q, J = 7Hz), 7.34 (5H,
m), 8.66 (1H, s) Reference example 6 4-amino-2-(4-benzylpiperazino)-
Piperazine-5-carboxylic acid ethyl ester 1-amidino-4-benzylpiperazino sulfate
26.8g and 3% sodium hydroxide solution in ethanol
Mix 133ml and then add ethyl-2-cyano-3
- 17.0 g of ethoxy acrylate was added. After refluxing for 5 hours, the mixture was allowed to cool. After ethanol was distilled off from the reaction mixture, water and ethyl acetate were added and the mixture was shaken. Precipitated 2-(4-phenylpiperazino)-5
-Separate the white crystals of cyano-4-hydroxypyrimidine, separate the liquid oil and water, and dry the organic layer.
Concentration gave a solid. Ether was added to the solid matter, insoluble matter was removed, and the ether was distilled off to give 4-
11.2 g of pale yellow crystals of amino-2-(4-benzylpiperazino)-5-ethoxycarbonylpyrimidine
(Yield 33g) was obtained. Melting point 244-245℃ ¹ H-NMR (CDCl ₃ solution, δppm) 1.34 (3H, t, J = 7Hz), 2.46 (4H, m),
3.53 (2H, s), 3.86 (4H, m), 4.27 (2H,
q, J=7Hz), 7.32 (5H, m), 8.63 (1H,
s) Reference Example 7 2-(4-benzylpiperazino)-4-ethylaminopyrimidine-5-carboxylic acid 2-(4-benzylpiperazino)-4-ethylaminopyrimidine-5-carboxylic acid ethyl ester (compound synthesized in Reference Example S) 106.4g
(0.29mol), 85% potassium hydroxide 38.0g
(0.58 mol), 100 ml of water, and 400 ml of ethanol were refluxed for 1 hour, and the ethanol was distilled off under reduced pressure.
Water was added and the mixture was neutralized with concentrated hydrochloric acid. The precipitated crystals were separated and dried to obtain 80.3 g of the title compound (yield: 82%). Melting point 158-160℃ ^1H -NMR spectrum (DMSO- _d6 solution,
δppm) 1.18 (3H, t, J=7Hz), 2.66 (4H, m),
3.44 (2H, dq, J=7Hz), 3.75 (2H, m),
3.91 (4H, m), 7.35 (5H, s), 8.19 (1H,
br.t, J=5Hz), 8.45 (1H, s) The following compound was synthesized by the same method. Structural formula R=NH ₂ (mp158-160°C (synthesized from the compound of Reference Example 6) NHCH ₃ (mp184-186°C) (synthesized from the compound of Reference Example 3) NHPr ⁱ (synthesized from the compound of Reference Example 3) OCH ₃ (mp208-210°C) (Synthesized from the compound of Reference Example 4) SCH ₃ (Synthesized from the compound of Reference Example 5) Example 1 2-(4-benzylpiperazino)-4-ethylaminopyrimidine-5-carboxylic acid diethylamide Add 0.2 ml of triethylamine to a mixture of 0.5 g (1.46 mmol) of 2-(4-benzylpiperazino)-4-ethylaminopyrimidine-5-carboxylic acid (compound synthesized in Reference Example 7) and 20 ml of chloroform.
(1.43 mmol) and then 0.22 ml of thionyl chloride.
(3.02 mmol) was added and stirred at room temperature for 1 hour. Next, add 1.0 ml (9.67 mmol) of diethylamine,
After further stirring for 1 hour, water was added and the mixture was extracted with chloroform. After drying the chloroform layer over anhydrous MgSO ₄ , the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column micromatography. ¹ H-NMR spectrum (CDCl ₃ solution, δppm) 1.20 (3H, t, J = 7Hz), 1.21 (3H, t, J
= 7Hz), 1.25 (3H, t, J = 7Hz), 2.48
(4H, m), 3.45 (6H), 3.54 (2H, s), 3.84
(4H, m), 6.98 (1H, br.t, J=5Hz), 7.32
(5H, s), 7.90 (1H, s) Various compounds of the present invention were synthesized in a similar manner. The results are shown in Table 2.

[Table] Example 12 2-(4-benzylpiperazino)-4-ethylaminopyrimidine-5-carboxylic acid dipropylamide hydrochloride Add 1.48 g of triethylamine to a mixture of 5 g (14.7 mmol) of 2-(4-benzylpiperazino)-4-ethylaminopyrimidine-5-carboxylic acid (compound synthesized in Reference Example 7) and 40 ml of dichloromethane.
(14.7 mmol) and further 22 ml of thionyl chloride.
(29 mmol) was added and stirred at room temperature for 1 hour. Next, 8.9g (88.2mmol) of dipropylamine was added,
After stirring for another 1 hour, 1N-NaOH aqueous solution 100%
After extraction with dichloromethane, 10 ml of concentrated hydrochloric acid was added to the dichloromethane layer, stirred, and then dichloromethane and water were distilled off. The residue was recrystallized from ethyl acetate-ethanol to obtain 3.14 g of the target product (yield 47%). ¹ H-NMR spectrum (DMSO-d ₆ liquid,
δppm) 0.82 (6H, t, J = 7Hz), 1.12 (3H, t, J
=7Hz), 1.5 (4H, m), 3.3 (14H, m),
4.36 (2H, s), 7.5 (5H, m), 7.80 (1H,
s), 8.1 (1H, brs) Example 13 2-Piperazino-4-ethylaminopyrimidine-5-carboxylic acid diethylamide 0.33 g of 2-(4-benzylpiperazino)-4-ethylaminopyrimidine-5-carboxylic acid diethylamide (compound synthesized in Example 1)
(0.83 mmol) in ethanol 20 ml, 99%
0.1 ml of formic acid, 0.1 g of 10% palladium on carbon as catalyst
Hydrolysis was carried out by refluxing for 1 hour. By filtering the catalyst and removing the refrigerant under reduced pressure, 0.26 g of the title compound was obtained as an oily product (yield ~100%). ¹ H-NMR spectrum (CDCl ₃ solution, δppm) 1.23 (9H), 3.36 (4H, m), 4.47 (6H), 4.21
(4H, m), 7.05 (1H, br.t, J=5Hz), 7.27
(5H, s), 7.90 (1H, s) The compounds shown in Table 3 were obtained in a similar manner.

【table】

[Table] Example 23 2-Piperazino-4-ethylaminopyrimidine-5-carboxylic acid dipropylamide A mixture of 3.14 g (6.9 mmol) of 2-(4-benzylpiperazino)-4-ethylaminopyrimidine-5-carboxylic acid dipropylamide, 10% Pd/0.31 g, and 50 ml of ethanol was heated at 60°C under a hydrogen atmosphere. Stirred for 1 hour. Separate 10% d/C, distill off the refrigerant,
20 ml of 1N NaOH aqueous solution was added to the residue, and the mixture was extracted with dichloromethane. After drying the dichloromethane layer over anhydrous sodium sulfate, dichloromethane was distilled off to obtain 2.11 g of the target product (yield 91%). ¹ H-NMR spectrum (CDCl ₃ solution, δppm) 0.88 (6H, t, J = 7Hz), 1.20 (3H, t, J
= 7Hz), 1.6 (5H, m), 2.91 (4H, t, J =
5Hz), 3.4 (6H, m), 3.81 (4H, t, J=5
Hz), 6.76 (1H, brs), 7.89 (1H, s) Example 24 2-(4-benzyloxycarbonylpiperazino)-4-methylthiopyrimidine-5-carboxylic acid diethylamide 2-(4-benzylpiperazino)-4-methylthiopyrimidine-5-carboxylic acid diethylamide
0.5 g was dissolved in 10 ml of tetrahydrofuran, and 0.3 g of benzyl chlorocarbonate was added dropwise thereto at room temperature, followed by further stirring at 45° C. for 12 hours. After cooling, tetrahydrofuran was distilled off under reduced pressure and extracted with chloroform.
The chloroform layer was dried over anhydrous magnesium sulfate and concentrated to obtain 0.5 g of the desired product. (Yield 89%). ¹ H-NMR spectrum (CDCl ₃ solution, δppm) 1.18 (6H, t, J = 7Hz), 2.51 (3H, s),
3,39 (4H, q, J=7Hz), 3.64 (4H,
m), 3.92 (4H, m), 4.58 (2H, s), 7.36
(5H, s), 7.95 (1H, s) Example 25 2-piperazino-4-methylthiopyrimidine-
5-carboxylic acid diethylamide 0.5 g of 2-(4-benzyloxycarbonylpiperazino)-4-methylthiopyrimidine-5-carboxylic acid diethylamide was dissolved in a 25% hydrogen bromide acetic acid solution and stirred at room temperature for 2 hours. hydrogen bromide,
Acetic acid and the resulting benzyl bromide were distilled off under reduced pressure, neutralized with a saturated aqueous sodium bicarbonate solution, extracted with chloroform, and dried over anhydrous magnesium sulfate. Chloroform was distilled off under reduced pressure and the residue was subjected to column chromatography to obtain 0.25 g of the desired product as a pale yellow oil (yield 71%). ¹ H-NMR spectrum (CDCl ₃ solution, δppm) 1.18 (6H, t, J = 7Hz), 2.50 (3H, s),
2.95 (4H, m), 3.40 (4H, q, J=7Hz),
3.87 (4H, m), 7.94 (1H, s) Test Example 1 Field Soil Treatment Test Field soil was filled in a porcelain pot with an inner diameter of 9 cm, and sowings of blueberry, blackberry, and Japanese cypress were sown. Immediately 300g of hydrating agent containing the specified compound per are
was dispersed in 20 liters of water and sprayed over the entire surface of the soil using a small sprayer from above the pot. After treatment, it was placed in a greenhouse for 20 days and its herbicidal efficacy was examined. The evaluation criteria are as follows. Weeding effect: 5 Complete death: 4 Weeding effect: Large 3 Herbicidal effect: Medium 2 Herbicidal effect: Small 1 Weeding effect: Slight 0 Ineffective (normal) The results are shown in Table 4.

[Table] Test Example 2 Paddy field test A porcelain pot with an inner diameter of 9 cm was filled with loose paddy soil, water was added, plowing was performed, and wild grass was sown to create a flooded state of 2 cm. The next day, a predetermined amount of a wettable powder prepared according to a predetermined formulation example was diluted with water and dripped into water (spraying amount: 250 g/10a).
The herbicidal efficacy of weeds was examined 20 days after chemical treatment. The evaluation criteria are as described above. The results are shown in Table 5.

【table】

Claims (1)

[Claims] 1. General formula [] [In the formula, R ¹ is hydrogen, a phenyl group-substituted methyl group, or a benzyloxycarbonyl group optionally substituted with a group selected from the group of halogen, alkoxy group, and nitro group, and R ² is -
NR ⁵ R ⁶ (R ⁵ and R ⁶ are each hydrogen or a lower alkyl group), OR ⁷ (R ⁷ is a lower alkyl group)
or ^-SR8 ( ^R8 is a lower alkyl group), and ^R3 and ^R4 are hydrogen or a lower alkyl group. ] A novel pyrimidine derivative.