DE2935578C2 - - Google Patents

Description

The invention relates to new pyrazolylpyrimidine derivatives of the general formula

wherein R₁ represents a hydrogen atom or an alkyl group, R₂ represents a hydrogen atom or a C _1-4 alkyl group, X represents an oxygen atom or a sulfur atom and R₃ represents a lower alkyl group, a phenyl group or a substituted phenyl group, with the proviso that, if R₁ is an alkyl group, R₂ represents a C _1-4 alkyl group and X represents a sulfur atom, R₃ represents an ethyl group or, if R₁ represents an alkyl group, R₂ represents a hydrogen atom and X represents an oxygen atom, R₃ is a substituted phenyl group. In addition, the invention relates to fungicides which are suitable for agriculture and gardening and contain at least one of the pyrazolyl pyrimidine derivatives mentioned.

Some compounds have been described which are similar to those of the above Formula I are similar, including 2- (3,5-dimethyl- 1-pyrazolyl) -4-methyl-6-hydroxypyrimidine, 2- (3,5-dimethyl-1- pyrazolyl) -4-phenyl-6-hydroxypyrimidine and 2- (3,5-dimethyl-1- pyrazolyl) -4-methyl-6-thiocyanopyrimidine. According to the Annual Report of the Takeda's Research Institute, volume 24, pages 250-258 (1965) these known compounds show activity fighting rice blast or mildew (rice blast), however, result in severe chemical damage.  

In the context of the invention, a number of pyrazolylpyrimidine Connections made and it was their usability as Investigated fungicides for agriculture and horticulture. It was found that the compounds of the above general formula I are new and when used as agricultural or horticultural fungicide a very strong one Combat effectiveness, especially against rice brandy or rice mildew, the brown rust of the rice (rice brown spot), cucumber powdery mildew and the like. Apart from the rice brandy or powdery mildew (Pyricularia oryzae), the brown rust of the rice (Cochliobolus miyabeanus) and the Cucumber powdery mildew (Sphaerotheca fuliginea) these compounds are highly effective against plant pathogens and in particular fungi or molds and so show one strong combating effect against the rotting of ripe grapes (Glomerella cingulata), citrus melanose (Diaporthe citri), Rotting chestnut (Endothia parasitica), rotting of the cucumber gummy stem blight (Mycosphaerell melonis), white bean stem rot (Sclerotinia sclerotiorum), Moniliosis of the apple (Sclerotinia fructigena), putrefaction of the rice leaf sheaths (Pellicularia sasakii), citrus green mold (Penicillium digitatum), cucumber gray mold (Botrytis cinerea), barley streak disease (Helminthosporium gramineum), "black belly rice kernel" (Alternaria padwikii, Curvularia sp.), rice leaf rust (Fusarium nivale), Root burn of cabbage (Phoma Lingam), "damping off" disease the egg fruit (Rhizootonia solani) and the like.

A number of the compounds according to the invention show a strong one fungicidal effect without chemically damaging crops. Furthermore, the connections are for humans, for animals or fish are non-toxic and can be safe and excellent can be used as fungicides.

These features of the invention can be found in the prior art the above-mentioned literature itself not by the skilled person remove. The new compounds according to the invention are as  versatile fungicides for agriculture and gardening usable.

The following is the preparation of the compounds according to the invention described in more detail.

The compounds of formula I can according to the following Reak equation:

wherein R¹, R², R³ and X each have the above Be have interpretations.

The compound of formula II can be conveniently by reaction a corresponding 6-hydroxy compound with phosphorus oxychloride in the usual manner, as in the Japanese patent publication 39-4493.

The reaction of the compound of formula II and the compound Formula III is complete without the use of a solvent feasible, but it is preferably in a solvent performed. In some cases, the compound of formula III be suitable as a solvent, but include commonly used ones Solvents organic solvents, such as hydrocarbons, halogenated hydrocarbons, ethers, esters, acid amides, Alcohols, dimethyl sulfoxide and the like and water. To carry out the reaction smoothly, use is preferably made  an acid binding agent. Examples of such acid-binding Agents include organic amines such as triethylamine, pyridine and the like, inorganic bases such as potassium carbonate, sodium hydroxide and the like and metallic sodium, metallic Potassium, sodium alkoxide, potassium alkoxide, sodium hydride, sodium amide and the same. The compound of formula III can precede reacted with the acid-binding agent and then be isolated, for example as the sodium salt, whereupon a Reaction with the compound of formula II takes place.

Although the reaction proceeds at room temperature, it is preferred to carry out the reaction under heating conditions, to shorten the response time. The response time varies with the type of compound of formula III and the solvent and the reaction temperature applied, however, the reaction when using a polar solvent inside ended in a short time. After the reaction has ended, the salts of the acid-binding agent that precipitated in the reaction solution are removed by filtration and then the solvent is removed from the filtrate by distillation, to obtain the compound of the invention. Alternatively, you can the reaction mixture with a mixture of a solvent, such as benzene, chloroform, ether, tetrahydrofuran or the like with water to complete the desired connection Get extraction.

The synthesis of the compounds of the invention is shown in the following Examples 1-6 described in more detail.

Example 1 (Preparation of Compound No. 4)

20.9 g of 2- (3,5-dimethyl-1-pyrazolyl) -6-chloropyrimidine, 11.0 g Thiophenol, 13.8 g of anhydrous potassium carbonate and 100 ml of di methyl sulfoxide was placed in a 300 ml flask and stirred at 80 ° C for one hour. After cooling, benzene and water was added to the reaction system and the organic Layer was won. The organic layer was treated with anhydrous Sodium sulfate dried and under reduced pressure  distilled to remove the solvent, 26.8 g the title compound as a light yellow oily substance with a Refractive index n of 1.6284 was obtained.

The substance crystallized on standing at room temperature gradually and then became from a mixed solvent recrystallized from cyclohexane and carbon tetrachloride with formation of white crystals of mp = 75-77 ° C.

Example 2 (Preparation of Compound No. 27)

Example 1 was repeated, replacing the thiophenol 12.2 g of 2,4-dimethylphenol were used; 29.9 g were obtained the title compound in the form of light yellow crystals. The Compound was recrystallized from cyclohexane to obtain of crystals of F. = 92.5-93.5 ° C.

Example 3 (Preparation of Compound No. 21)

22.3 g of 2- (3,5-dimethyl-1-pyrazolyl) -4-methyl-6-chloropyrimidine, 18.4 g sodium m-trifluoromethylphenolate and 100 ml dimethyl formamide were placed in a 300 ml flask and three Stirred at 80 ° C for hours. After cooling, benzene and Water was added to the reaction system and the organic layer was removed. The organic layer was treated with anhydrous Dried sodium sulfate and the solvent was evaporated through Distill under reduced pressure to form of 32 g of the title compound in the form of light yellow crystals. The compound was made from a mixed solvent of Cyclohexane and acetone recrystallized to form white Crystals of mp = 117-118 ° C.

Example 4 (Preparation of Compound No. 32)

100 ml of absolute ethanol was placed in a 300 ml flask, and 2.3 g of metallic sodium became the reaction added. Then 22.3 g of 2- (3,5-dimethyl-1-pyrazolyl) - 5-methyl-6-chloropyrimidine added to the reaction system and stirring was carried out for one hour at room temperature. The right the resulting salt was removed by filtration and the filtrate  was concentrated to give 22.3 g of the title compound in the form of white crystals. The connection was made recrystallized from hexane to obtain white crystals F. = 78-79 ° C.

Example 5 (Preparation of Compound No. 41)

Example 4 was repeated using 27.9 g of 2- (3.5- Dimethyl-1-pyrazolyl) -4-methyl-5-n-butyl-6-chloropyrimidine instead des 2- (3,5-dimethyl-1-pyrazolyl) -5-methyl-6-chloropyrimidine, whereby 26.8 g of the title compound in the form of light yellow Received crystals. The connection was made from a Lö Mixture of cyclohexane and carbon tetrachloride recrystallized to form crystals of mp = 59-61 ° C.

Example 6 (Preparation of Compound No. 42)

27.9 g of 2- (3,5-dimethyl-1-pyrazolyl) -4-methyl-5-n-butyl-6-chloro pyrimidine, 7.0 g ethyl mercaptan, 13.8 g anhydrous potassium carbonate and 150 ml of dimethyl sulfoxide were placed in a 300 ml Flask inserted, followed by stirring at 40 ° C for eight hours. After cooling, benzene and water became the reaction system added and the organic layer was removed. The organic Layer was dried with anhydrous sodium sulfate and the solvent was reduced by distillation under reduced pressure Pressure removed to give 27.1 g of the title compound in the form of a light yellow oily substance. The connection had a refractive index n of 1.5718.

The compounds of general formula I as in the above Examples are made in Table 1 below listed.  

Table 1

To use the compounds according to the invention for combating of plant diseases of agricultural and horticultural Useful plants can use the compounds as such or diluted with a suitable carrier, such as water or a solid Powder to which an adjuvant has optionally been added, such as a spreader. Alternatively, you can the connections with different types of liquids or solid carriers are mixed, as is usually the case Production of agricultural chemicals is carried out. Optionally, additives such as a wetting agent Spreader, a dispersant, an emul yaw, a binder and the like are added to the mixture are used in the form of different types of preparations, such as wettable powders, solutions, emulsions, dusts, granules, fine granules.

When preparing these chemicals are used as a liquid carrier Water, aromatic hydrocarbons, aliphatic carbons Hydrogens, alcohols, esters, ketones and highly polar solvents, such as dimethylformamide, dimethyl sulfoxide and the like used; mineral or inorganic as solid carrier Powder, such as alumina, talc, kaolin, bentonite, diatomaceous earth, Silica and the like and organic powders such as wood flour or sawdust; and as an additive non-ionic, anionic, cationic and amphoteric surfactants, lig ninsulfonic acid or its salts, gums, fatty acid salts, pastes, such as methyl cellulose and the like.

The agricultural and horticultural invention Fungicide can be applied directly to the plants to be treated will. Alternatively, it may be based on the location a plant, like a water surface or a soil surface can be applied or can be incorporated into the Use the floor. Is the fungicide according to the invention in liquid form used, it preferably contains it Compound according to the invention in a concentration of 10 to 1000 ppm in a spray liquid. In the case of a "minor Amounts of concentrate "sprays or an aircraft spray can be used  concentrated liquid can be used. in case of a Dust, a granulate and a fine granulate is the Compound preferably contained in an amount of 0.1 to 30%.

The invention will now be described in more detail by means of examples explains the agricultural and horticultural fungicides concern, but should not constitute a limitation.

Example 7 (wettable powder)

20 parts by weight of compound no. 2, 5 parts by weight of polyoxyethylene alkyl aryl ether, 3 parts by weight of calcium lignin sulfonate and 72 parts by weight Parts of diatomaceous earth were ground and mixed evenly to obtain a wettable powder that is 20% of the effective Constituent contained.

Example 8 (granules)

5 parts by weight of Compound No. 19, 1 part by weight of calcium lignin sulfonate, 30 parts by weight of bentonite and 64 parts by weight of alumina evenly pulverized, water was in a suitable Amount added, then kneaded and granulated to obtain granules containing 5% of the active ingredient.

Example 9 (dust)

3 parts by weight of compound no. 10, 0.5 parts by weight of fine powder siliconized dioxide, 0.5 part by weight of calcium stearate, 50 parts by weight of alumina and 46 parts by weight of talc became uniform mixed to achieve a dust that is 3% of the effective Constituent contained.

Example 10 (emulsion)

20 parts by weight of compound no. 1, 30 parts by weight of dimethylformamide, 35 parts by weight of xylene and 15 parts by weight of polyoxyethylene alkyl aryl ethers were mixed evenly to obtain one Emulsion containing 20% of the active ingredient.

Trial 1 (Investigation of the effectiveness in combating (Ver hindrance) from rice brandy, "rice blast")

To the seedlings of a rice plant (variety: Asahi), which  third leaf stage had grown and in an unglazed Pot with a diameter of 9 cm in the greenhouse in the ground a test liquid was sprayed, those by dispersing each of those prepared as in Example 7 wettable powder in a predetermined concentration had been preserved. One day after spraying, one was Spore suspension of Pyricularia oryzae via the seedlings Sprayed inoculation. After the inoculation, the pot was in put a moist chamber and overnight at 24 to 25 ° C kept under a relative humidity of 95 to 100%. Five days after the inoculation, the number of injuries examined per leaf of the third leaf level and it was a control value is calculated from the following equation. The chemical Injuries to the rice plant were identified as follows Equation evaluated. The test results are in the Table 2 listed.

Chemical Injury Assessment Standard:
5: very strong
4: strong
3: pretty
2: something
1: easy
0: none

Table 2 (Effect of fire fighting)

In the table above, the comparison chemicals 1 2 or 3 wettable powders produced as in Example 7 and 2- (3,5-dimethyl-1-pyrazolyl) -4-methyl-6-hydroxy pyrimidine, 2- (3,5-dimethyl-1-pyrazolyl) -4-phenyl-6-hydroxy pyrimidine and 2- (3,5-dimethyl-1-pyrazolyl) -4-methyl-6-thio contain cyanopyrimidine and the comparison chemical is 4 a commercially available fungicide (under the trade name Kitazin P Emulsion) containing 0.0-diisopropyl-S-benzylphosphorothiolate.

Trial 2 (Investigation of the effect of fighting rice fire (Cure))

A spore suspension of Pyricularia oryzae was sprayed for inoculation over seedlings of rice plants (variety: Asahi) which had been grown up to the third leaf stage in a soil culture in an unglazed pot with a diameter of 9 cm in a greenhouse. After the inoculation, the pot was placed in a humidity chamber and kept at 24 to 25 ° C under a relative humidity of 95 to 100%. One day after the inoculation, each of the test liquids, which had been diluted to a predetermined concentration, was sprayed over the seedlings. 5 days after spraying, the control value and the degree of chemical damage were determined in the same manner as in Experiment 1; the results are shown in Table 3 below.

Table 3 (Effect of the fire healing treatment)

In the above table, 1, 2, 3 and 4 used the one specified in experiment 1.

Trial 3 (Study of the effectiveness in combating the brown rice grate)

Each of the liquids to be examined was diluted to a predetermined concentration, over seedlings of a rice plant (Variety: Asahi) sprayed up to the 4-leaf stage in one Soil culture in an unglazed pot with a diameter of 9 cm had been raised in a greenhouse. One Day after spraying, a conidiospore suspension of Cochliobolus miyabeanus sprayed over the seedlings for inoculation. 5 days after the inoculation, the number of ver and examined the results per leaf of the 4th leaf stage Control value was calculated from the following equation. The The extent of chemical damage to the rice plant was the same Way as evaluated in experiment 1. The investigation results are listed in Table 4.

Table 4 (Effect of combating brown rust)

In the table above, the comparison chemicals 1 2 and 3 the same as in experiment 1 and in the comparison chemical 4 is a commercially available bactericide (called triazines), the 2,4-dichloro-6- (O-chloroanilino) - Contains 1,3,5-triazine.

Trial 4 (Study of the effectiveness in combating the Cucumber powdery mildew, "powdery mildew")

10 ml of each of the test liquids diluted to a predetermined one Concentration, was about seedlings of a cucumber plant (variety: Sagami Hanpaku) sprinkled in until the first leaf stage a soil culture in an unglazed pot with a diameter of 9 cm were grown in a greenhouse. After standing overnight, the seedlings became inoculation sprayed with a spore suspension of Sphaerotheca friliginea. 10 days after the inoculation, the extent of an injury area (%) was evaluated and a control value was obtained from the following Equation determined. The extent of chemical damage to a Cucumber plant was determined in the same manner as in Experiment 1. The results are shown in Table 5 below.

Table 5 (Effect of mildew control)

In the table above, chemicals 1 and 2 correspond Comparative Chemicals 1 and 3 of Experiment 1 and Ver same chemical 3 is a commercially available liquid (milcurb) which contains 2-dimethylamino-4-methyl-5-butyl-6-hydroxypyrimidine.

Trial 5 (Investigation of antimicrobial activity against various plant pathogenic fungi)

1 ml of an acetone solution of each of the test compounds and 20 ml PDA medium (50 ° C) were used to manufacture media that the Chemical contained in various concentrations, used followed by a petri dish with a diameter of 9 cm was filled, where there was a flat solidification. On the central part of the medium containing the chemical became a medium containing fungus, a piece of agar soot (ager black) inoculated mycelium, which by cutting the final portion of the mycelium of each test fungus preceding that grown in the PDA medium with a cork borer was obtained, followed by culturing at 24 ° C has been. The diameter became 2-6 days after cultivation of the mycelium and the extent of inhibition of the mycelium growth was from a comparison with an untreated Piece calculated. The extent of mycelial growth inhibition was used to determine an ED₅₀ value on a logarithmic Paper applied. The test results are in the Table 6 below.  

Table 6 (Antimicrobial activity against various phytopathogenic fungi)

Claims (3)

1. Pyrazolylpyrimidine derivative of the general formula wherein R₁ represents a hydrogen atom or an alkyl group, R₂ represents a hydrogen atom or a C _1-4 alkyl group, X represents an oxygen atom or a sulfur atom and R₃ represents a lower alkyl group, a phenyl group or a substituted phenyl group, with the proviso that, if R₁ is an alkyl group, R₂ represents a C _1-4 alkyl group and X represents a sulfur atom, R₃ represents an ethyl group or, if R₁ represents an alkyl group, R₂ represents a hydrogen atom and X represents an oxygen atom, R₃ represents a substituted phenyl group. 2. Fungicide, suitable for use in agriculture and in horticulture containing an effective amount of a pyrazolyl pyrimidine derivative according to claim 1.   3. A process for the preparation of a compound of the general formula according to claim 1, characterized in that a compound of formula II wherein R₁ and R₂ have the meanings given in claim 1 with a compound of the formula IIIR₃XH (III) wherein X has the meaning given in claim 1, in the presence or absence of a solvent in the presence or absence of an acid-binding agent.