JPH06764B2 - 2-Piperazinopyrimidine derivative - Google Patents

Description

TECHNICAL FIELD The present invention relates to a novel 2-piperazinopyrimidine derivative useful as a herbicide.

[Conventional technology]

A compound in which a ring containing nitrogen or carbonyl is condensed with a pyrimidine ring, for example, as a compound having a pyridopyrimidine structure, Chemical Abstracts (Chem. Abstr.) Vol. 90, 54893 (197).
9), Vol. 97, 182350 (1982). However, there is a great difference in structure from the compound of the present invention, and the usefulness of these known compounds for agricultural use has not been clarified at all.

[Outline of Invention]

The present invention has the general formula [I] [In the formula, R ¹ is hydrogen or an aralkyl group, R ² and R ³ are the same or different and each represents a lower alkoxy group, a hydroxyl group or a lower alkylamino group, or R ² and R ³ are the same. Is a lower alkyl group-substituted imino group. ] The present invention relates to a 2-piperazinopyrimidine derivative represented by

[Substance of the present application]

The substance of the present application is represented by the general formula [I], and as the aralkyl group of R ^{1 in} the formula, a benzyl group, a diphenylmethyl group, a triphenylmethyl group and the like can be mentioned.
Especially, a benzyl group is preferable.

Further, examples of the lower alkoxy group for R ² or R ³ include a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group and a butoxy group, and among them, an ethoxy group is particularly preferable. Further, as the lower alkylamino group for R ² or R ³ , methylamino group, ethylamino group, n-propylamino group, isopropylamino group, n
-Butylamino group, isobutylamino group, sec-butylamino group, tert-butylamino group and the like can be exemplified, and among them, ethylamino group is particularly preferable. Examples of the lower alkyl group of the lower alkyl group-substituted imino group include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, and the like. In particular, an ethyl group is preferable.

Further, the substance of the present application may be in a free state or in a salt form, for example, an acid addition salt form. Such salts can also be used as herbicides. Examples of the acid addition salt include mineral acids such as hydrochloric acid, sulfuric acid and phosphoric acid, and organic acids such as acetic acid, maleic acid and citric acid.

Among the substances of the present application, the compounds described in Examples below can be exemplified as particularly preferable ones.

〔Production method〕

The substance of the present invention represented by the general formula [I] can be produced according to the following reaction formula. A typical substance of the present application will be described as an example.

As the above compound, those obtained by the method described in J. Am. Chem. Soc., 73 , 3685 (1951) can be used. As the solvent for producing the compound, those inert to the reaction such as methanol, ethanol, propyl alcohol, tetrahydrofuran, water, benzene, toluene, xylene and ether can be used. The molar ratio of the compound to the compound used is usually 0.5 to 1.5, preferably 0.8 to 1.2, and the molar ratio of the compound used to sodium ethoxide is the same. The reaction temperature is 0 to 150 ° C, preferably 0.
Incubate at -80 ° C for 0.5-50 hours. The specific operation is as in the example described later.

In order to produce a compound, DMF can be used as a reaction solvent in addition to the above-mentioned solvents.
It is preferable to use F, and the molar ratio of the compound to the compound is usually 2 to 10, preferably 2 to 5, and the temperature is 100 to 200 ° C, preferably 120 to 180 ° C for 15 minutes to 15 hours, preferably Incubate for 0.5 to 3 hours.

In order to produce a compound or a compound in which R ¹ is hydrogen, each compound can be obtained by hydrogenolysis. As the hydrocracking catalyst, Pd-C, Raney-Ni, Pt
-Use C, Pdo, etc. The reaction solvent is an alcohol such as methanol, ethanol or isopropanol, a carboxylic acid such as formic acid, acetic acid or propionic acid, or a mixed solvent such as ethanol-formic acid or ethanol-acetic acid, and hydrogen is supplied at atmospheric pressure or 10 kg / cm ^2. , 10 to 100 °
React with C for 0.1 to 10 hours. After the reaction, the target compound can be obtained by a conventional method. The same applies to the hydrogenolysis of the compounds described below.

Among the substances of the present invention represented by the general formula [I], those in which R ² and R ³ are both hydroxyl groups can be produced by hydrolyzing the substance of the present invention in which both R ² and R ³ are lower alkoxy. A prime example is shown.

Examples of the base used in this reaction include inorganic bases such as sodium hydroxide, potassium hydroxide and calcium hydroxide, and tertiary amines such as triethylamine and pyridine. It is used in the range of 4 to 4 times mol. Water is usually used in an amount of 1 to 10,000 times the molar amount of the compound. As the reaction solvent, lower alcohols such as methanol, ethanol, isopropyl alcohol and n-propyl alcohol, dioxane, tetrahydrofuran, DMF and DMSO can be used. The reaction is usually carried out at a temperature of -10 to 100 ° C, preferably 0 to 50 ° C for 0.5 to 48 hours.

Among the substances of the present application, R ² is a lower alkylamino group,
R ³ is a hydroxyl group may be prepared from compounds wherein R ² and R ³ are both hydroxyl. The following is a typical example.

In the reaction solvent, 1 to 10 mol of thionyl chloride, preferably 1 to 4 mol, and 0.5 to 20 mol of triethylamine, preferably 0.8 to 12 mol, per 1 mol of the compound.
The reaction is carried out at a temperature of -10 to 100 ° C, preferably 0 to 50 ° C for 5 minutes to 10 hours, preferably 30 minutes to 2 hours. As the solvent, those which are stable under the reaction conditions such as benzene, toluene, xylene, dichloromethane, chloroform, DMF, DMSO, THF, ether, dioxane and ethyl acetate can be used. To the above reaction solution, triethylamine was further added in an amount of 1 to 100 mol, preferably 3 to 80 mol, and ethylamine in an amount of 1 to 100 mol, preferably 3 to 80 mol, at the same temperature and time as in the first step. React.

Among the substances of the present application, those in which R ² and R ³ together are a lower alkyl group-substituted imino group can be typically produced from a compound as follows.

0.01 to 1 mol, preferably 0.4 to 0.7 mol, of potassium acetate is used per 1 mol of the compound, and 1 to 20 mol, preferably 5 to 15 mol of acetic anhydride is used, and the temperature is 80 to 180 ° C, preferably At 120 to 160 ° C
The reaction is carried out for 0.1 to 10 hours, preferably 0.5 to 3 hours. At this time, a solvent is not always necessary, but a solvent which is stable under the reaction conditions such as benzene, toluene, xylene, hexane, ether, THF, acetic acid, ethyl, DMF, DMSO can be used.

〔Usefulness〕

The substance of the present invention has excellent activity as a herbicide. That is, the substance of the present application can be used as a paddy field and upland herbicide. The weeds to be used as herbicides are particularly effective against paddy field weeds such as Taenia japonicus, Tamagawai, Konagi, firefly, Hera modada, etc., and field weeds such as barnyardgrass, Japanese cedar, Pleurotus ostreatus, Aoyu, Kogomeka citrus, and Shiloza.

To use the substance of the present invention as a herbicide, the substance of the present invention alone or in combination with a carrier, a surfactant, a dispersant, an auxiliary agent, etc., is formulated into a hydrate, an emulsion, a fine granule or a granule, and the like. Dilute to different concentration and spray or apply directly.

Hereinafter, the present invention will be specifically described with reference to Examples and the like.

[Examples, etc.]

Example 1 2- (4-benzylpiperazino) -4,5-pyrimidinedicarboxylic acid diethyl ester While dissolving 0.91 g of sodium in absolute ethanol, 1
-11.5 g of amidino-4-benzylpiperazine sulfate was added, and the mixture was stirred at room temperature for 30 minutes. To this was added 8.8 g of ethyl ethoxymethylene oxaloacetate (synthesized by the method described in J. Am. Chem. Soc., 73,3684 (1951).) After reacting for 2 days at room temperature, it was heated under reflux for 1 hour. Reacted After cooling to room temperature, ethanol was distilled off under reduced pressure, and the residue was dissolved in water and ethyl acetate. After separating the aqueous layer, the ethyl acetate layer was washed with water and saturated brine. After drying over magnesium sulfate, ethyl acetate was distilled off under reduced pressure to obtain 13.7 g of pale and colored crystals of the title compound (yield 96%).

Melting point: 66 ° C Infrared absorption spectrum (nujol, cm ^-1 ) 1750,1715,1590. ¹ H-NMR spectrum (CDCl ₃ , δppm) 1.32 (3H, t, J = 7Hz), 1.39 (3H, t, J = 7Hz), 2.49 (4H, t, J = 5H
z), 3.54 (2H, s), 3.94 (4H, t, J = 5Hz), 4.30 (2H, q, J = 7Hz), 4.
42 (2H, q, J = 7Hz), 7.31 (5H, s), 8.85 (1H, s). Example 2 N, N'-diethyl-2- (4-benzylpiperazino) -4,5- Pyrimidinedicarboxylic acid amide 2- (4-) synthesized in Example 1 in an autoclave
Benzylpiperazino) -4,5-pyrimidinedicarboxylic acid diethyl 1.5 g, ethylamine 1 ml, DMF 20 ml were added, and 1
The reaction was carried out at 50 ° C for 1 hour. After the reaction, DMF was distilled off, and 20 ml of hexane and 5 ml of ethyl acetate were added to the residue to give pale yellow crystals of the title compound produced by filtration (yield 0.8 g,
Yield 54%).

Melting point: 201 ° C infrared absorption spectrum (nujol, cm ^-1 ) 3290,1650,1635,1585. ¹ H-NMR spectrum (CDCl ₃ , δppm) 1.23 (3H, t, J = 7Hz), 1.24 (3H, t, J = 7Hz), 2.54 (4H, t, J = 5H
z), 3.46 (2H, q, J = 7Hz), 3.49 (2H, q, J = 7Hz), 3.56 (2H, s), 3.89 (4H, t, J = 5Hz), 7.32 (5H, s), 7.6 (1H, brs), 9.16 (1H, s), 9.5 (1H, brs). Example 3 2- (4-benzylpiperazino) -4,5-pyrimidinedicarboxylic acid 2- (4-benzylpiperazino) -synthesized in Example 1
Diethyl 4,5-dicarboxylate and 0.84 g of potassium hydroxide were reacted overnight in a mixed solvent of 20 ml of ethanol and 5 ml of water. After the reaction, ethanol was distilled off under reduced pressure, the residue was dissolved in 100 ml of water, and the pH of the mixture was adjusted to pH 4 with concentrated hydrochloric acid to obtain white crystals of the title compound (yield 1.72 g, yield 100).
%).

Melting point: 300 ° C Infrared absorption spectrum (nujol, cm ^-1 ) 1720,1680,1580. ¹ H-NMR spectrum (DMSO-d ₆ , δppm) 3.22 (4H, brs), 4.16 (4H, brs), 4.31 (2H, s), 7.4-7.8 (5H, m), 8.88 (1H, s). Example 4 N-Ethyl-2- (4-benzylpiperazino) -4-carbamoyl-5-pyrimidinecarboxylic acid 2- (4-benzylpiperazino) -synthesized in Example 3
Dichloromethane 5 was added to 1.70 g of 4,5-pyrimidinedicarboxylic acid.
0 ml was added, and 1.01 g of triethylamine and 0.75 ml of thionyl chloride were further added and reacted for 1 hour. To this reaction solution, 6.06 g of triethylamine and 0.18 g of ethylamine were added, and the reaction was further continued for 1 hour. The reaction solution was put into water, the dichloromethane layer was separated, and the aqueous layer was extracted with dichloromethane. The dichloromethane layer and the extract were combined, dried over magnesium sulfate, and then the dichloromethane was distilled off under reduced pressure to obtain 1.5 g of the title compound as yellow crystals (yield 81%).

Melting point: 242 ° C infrared absorption spectrum (nujol, cm ^-1 ) 1705,1508. ¹ H-NMR spectrum (DMSO-d ₆ , δppm) 1.09 (3H, t, J = 7Hz), 2.8-4.0 (10H, m), 4.30 (2H, s), 7.4 to 7.8 (5H, m), 8.45 (1H, t, J = 6Hz), 8.83 (1H, s). Example 5 N-ethyl-2- (4-benzyl) Piperazino) -4,5-pyrimidinedicarboxylic acid imide To 1.5 g of N-ethyl-2- (4-benzylpiperazino) -4-carbamoyl-5-pyrimidinecarboxylic acid synthesized in Example 4, 0.24f of potassium acetate and 5 ml of acetic anhydride were added, and the mixture was heated and refluxed for 1.5 hours. . Acetic anhydride and acetic acid were distilled off under reduced pressure, water was added to the residue, and the mixture was stirred for 2 hours to obtain 0.5 g of the title compound as yellow crystals, which was obtained by filtration (yield 36
%).

Melting point: 124 ° C infrared absorption spectrum (nujol, cm ^-1 ) 1770,1710,1620,1540. ¹ H-NMR spectrum (CDCl ₃ , δppm) 1.25 (3H, t, J = 7Hz), 2.64 (4H, br), 3.69 (2H, s), 3.73 (2H, q, J = 7Hz), 4.13 (4H, brs), 7.36 (5H, s), 8.70 (1H, s) .Example 6 2-Piperazino-4 Diethyl 5,5-pyrimidinecarboxylic acid 2- (4-benzylpiperazino) -synthesized in Example 1
Diethyl 4,5-pyrimidinedicarboxylate (1.5 g) was dissolved in ethanol (20 ml) and acetic acid (5 ml), 10% Pd-C (0.15 g) was added, and the mixture was stirred at 70 ° C for 1 hr under hydrogen atmosphere. After the reaction, ethanol and acetic acid were distilled off under reduced pressure, the residue was dissolved in dichloromethane and washed with saturated aqueous sodium hydrogen carbonate. Dichloromethane was distilled off under reduced pressure to obtain 0.97 g of the title compound as a yellow oil (yield 81%).

Infrared absorption spectrum (neat, cm ^-1 ) 2980,1745,1715,1590,1540,1290,1250. ¹ H-NMR spectrum (CDCl ₃ , δppm) 1.33 (3H, t, J = 7Hz), 1.40 (3H, t, J = 7Hz), 2.03 (1H, brs), 2.9
2 (4H, t, J = 5Hz), 4.31 (2H, t, J = 7Hz), 4.43 (2H, t, J = 7Hz), 8.87 (1H, s) Example 7 N, N′-diethyl- 2-piperazino-4,5-pyrimidinedicarboxylic acid amide 0.8 g of N, N'-diethyl-2- (4-benzylpiperazino) -4,5-pyrimidinecarboxylic acid amide synthesized in Example 2 was dissolved in 30 ml of ethanol, and 0.08 g of 10% Pd-C was added. And stirred at 60 ° C for 4 hours under hydrogen atmosphere. After 10% Pd-C was filtered off, ethanol was distilled off under reduced pressure to obtain pale yellow crystals of the title compound (yield 0.55 g, yield 89%).

Melting point: 73 ° C infrared absorption spectrum (KBr, cm ^-1 ) 3300,1640,1585,1520,1450,1265. ¹ H-NMR spectrum (CDCl ₃ , δppm) 1.24 (3H, t, J = 7Hz), 1.26 (3H, t, J = 7Hz), 1.76 (1H, brs), 2.9
4 (4H, t, J = 5Hz), 3.42 (2H, dt, J = 7Hz, 2Hz), 3.49 (2H, dt, J = 7
Hz, 2Hz), 3.86 (4H, t, J = 5Hz), 7.6 (1H, brs), 9.16 (1H, s), 9.
5 (1H, brs).

Claims (1)

☆ Ming [Claims] 1. A general formula [I] [In the formula, R ¹ is hydrogen or an aralkyl group, R ² and R ³ are the same or different and each represents a lower alkoxy group, a hydroxyl group or a lower alkylamino group, or R ² and R ³ are the same. Is a lower alkyl group-substituted imino group. ] The 2-piperazino pyrimidine derivative represented by these.