CN110305115A - Preparation and application of a pyrazole oxime derivative containing 1-(6-chloropyrazin-2-yl)-3-methoxypyrazole unit - Google Patents

Abstract

The present invention relates to the preparations and application of a kind of pyrazoles 9 oxime derivate (I) containing 1- (6- chloropyrazine -2- base) -3- methoxyl group pyrazoles unit.It is condensed to yield by pyrazoles formoxyl chlorine (II) and pyrazoles oxime (III).The pyrazoles 9 oxime derivate containing 1- (6- chloropyrazine -2- base) -3- methoxyl group pyrazoles unit has effective control efficiency to harmful insect, which can be used for preparing the insecticide in the fields such as agricultural, gardening.

Description

A derivative of pyrazole oxime containing 1-(6-chloropyrazin-2-yl)-3-methoxypyrazole unit preparation and application of

technical field

The invention relates to the field of chemical pesticides, in particular to the preparation and application of a pyrazole oxime derivative containing a 1-(6-chloropyrazin-2-yl)-3-methoxypyrazole unit.

Background technique

Pest control has always been the core field of pesticide scientific research, and the widespread use of insecticides has enabled most pests to be effectively controlled. However, with the continuous expansion of the application scale of pesticides, the problem of resistance to traditional pesticides has become increasingly prominent, coupled with the continuous emergence of new pests and diseases, making the continued research and development of new pesticides an inevitable choice.

Nitrogen-containing heterocyclic rings are widely used in agricultural production. As an important class of nitrogen-containing heterocyclic compounds, pyrazole oxime derivatives have excellent insecticidal and acaricidal activities. play an important role in insecticide.

Pyrazole rings are also widely used in agricultural production. Substituted pyrazole compounds have excellent insecticidal and acaricidal activities. Pyrazole heterocycles are widely introduced into pesticide compound molecules, such as pyrazole amides insecticidal The acarids tebufenpyrad and tolfenpyrad have excellent killing activity against mites and aphids (Biochim. Biophys. Acta 1998, 1364, 236-244).

Therefore, in order to further search for compounds with excellent biological activity from pyrazole oxime compounds, the active group splicing method is used to rationally link the substituted pyrazole unit structure with the pyrazole oxime skeleton. Pyrazole oxime derivatives containing 1-(6-chloropyrazin-2-yl)-3-methoxypyrazole units of value for insecticidal applications.

Contents of the invention

The purpose of the present invention is to provide a class of pyrazine containing 1-(6-chloropyrazin-2-yl)-3-methoxypyrazole unit which has excellent control effect against various pests and is highly efficient, safe and environment-friendly. Azoxime derivatives to meet the demand for high-efficiency insecticides for crop protection.

Another object of the present invention is to provide the use of the above compounds in the preparation of pesticides.

Another object of the present invention is to provide the preparation method of the above compound.

In order to solve the above technical problems, the first aspect of the present invention provides a preparation and application of a pyrazole oxime derivative containing 1-(6-chloropyrazin-2-yl)-3-methoxypyrazole unit, which Has the general formula I structure,

Preferably, the pyrazole oxime derivative containing 1-(6-chloropyrazin-2-yl)-3-methoxypyrazole unit has the following structure:

The second aspect of the present invention provides the above-mentioned preparation method of a pyrazole oxime derivative containing 1-(6-chloropyrazin-2-yl)-3-methoxypyrazole unit, which comprises the following steps:

Dissolve compound III in an organic solvent, add an acid-binding agent, then add intermediate II, react for a period of time, filter the reaction solution with suction, concentrate the mother liquor under reduced pressure, and separate and purify the obtained residue to obtain the target compound.

Preferably, the acid-binding agent is selected from pyridine, sodium acetate, triethylamine, sodium carbonate and sodium bicarbonate, and the solvent is selected from N,N-dimethylformamide (DMF), acetonitrile, tetrahydrofuran (THF) , dichloromethane and chloroform. The heating reaction temperature is 0°C-100°C, and the reaction time is 10-22 hours.

Preferably, a preparation method of a pyrazole oxime derivative containing 1-(6-chloropyrazin-2-yl)-3-methoxypyrazole unit is as follows:

Wherein, the synthesis of the intermediate pyrazine bipyrazole carboxyl chloride refers to the conventional method reported in the literature (Organic Chemistry, 2011,31,1943-1948); the synthesis of the pyrazole oxime intermediate refers to the conventional method reported in the literature (J.Agric. Food Chem. 2008, 56, 10805-10810).

The compound of general formula I has excellent control activity on insects, so the compound of the present invention can be used to prepare insecticides, and further protect plants such as agriculture and gardening. Said insects include Lepidoptera pests such as cotton bollworm, beet armyworm, diamondback moth, cabbage caterpillar, rice leaf roller and rice stem borer, etc.; Homoptera pests such as leafhoppers, planthoppers, earthworms, whitefly , scale insects of the family Psyllididae, etc.; Diptera pests such as houseflies, leaf miners, mosquitoes, etc.; Orthoptera locusts, etc., Coleoptera beetles, scarabs, weevils, bean weevils, etc.; Wait. Of course, the harmful organisms that can be controlled by the compounds of the present invention are not limited to the scope of the above examples.

When the compound of the present invention represented by general formula I is used as an insecticide in fields such as agriculture and horticulture, it can be used alone or in the form of an insecticidal composition, such as using formula I as an active ingredient, plus the field Commonly used pesticide adjuvants are processed into aqueous emulsions, suspension concentrates, water-dispersible granules, emulsifiable concentrates, etc.

Commonly used pesticide adjuvants include: liquid carriers, such as water; organic solvents such as toluene, xylene, cyclohexanol, methyl alcohol, butanol, ethylene glycol, acetone, dimethylformamide, acetic acid, dimethyl sulfoxide, animal and Vegetable oils and fatty acids; commonly used surfactants such as emulsifiers and dispersants, including anionic surfactants, cationic surfactants, nonionic surfactants and amphoteric surfactants; other additives, such as wetting agents, thickeners, etc.

When the compound of the present invention represented by general formula I is used as an active ingredient in an insecticide, the content in the insecticide is selected within the range of 0.1% to 99.5%, and can be selected according to the formulation form and application method Determine the appropriate active ingredient level. Usually, contain 5% to 50% (weight percentage, the same below) described active component in aqueous emulsion, preferably its content is 10% to 40%; Contain 5% to 50% active component in suspension concentrate, preferably Its content is 5% to 40%.

For the use of the insecticide of the present invention, commonly used pesticide application methods can be selected, such as stem and leaf spray, water surface application, soil treatment and seed treatment and the like. For example, when spraying stems and leaves, the compound represented by the general formula I as an active ingredient can be used in aqueous emulsions, suspensions, water-dispersible granules, and emulsifiable concentrates in a concentration range of 1 to 1000 μg/mL, preferably at a concentration of 1 to 500 μg/mL.

A pyrazole oxime derivative containing 1-(6-chloropyrazin-2-yl)-3-methoxypyrazole unit disclosed by the present invention has an excellent control effect on harmful insects, so it can be used to prepare Insecticides in agriculture, horticulture and other fields.

Detailed ways

The above solution will be further described below in conjunction with specific embodiments. It should be understood that these examples are used to illustrate the present invention and not to limit the scope of the present invention. The implementation conditions used in the examples can be further adjusted according to the conditions of specific manufacturers, and the implementation conditions not indicated are usually the conditions in routine experiments.

Example 1:

8 mmol of compound IIIa was dissolved in 30 mL of acetonitrile, then 30 mmol of pyridine was added, and then 7 mmol of intermediate II was added thereto under ice-cooling conditions. After the addition was complete, the reaction was continued under reflux for 15 hours. The reaction was stopped, the reaction solution was rotary evaporated to dryness under reduced pressure, and the obtained residue was separated and purified by column chromatography to obtain the target compound Ia; ¹ H NMR (400MHz, CDCl ₃ ): δ8.62 (s, 1H, Pyrazine-H), 8.17(s, 1H, Pyrazine-H), 7.94(s, 1H, CH=N), 7.13～7.37(m, 3H, Ar-H), 6.88(d, J=8.0Hz, 2H, Ar-H) ,6.80(s,1H,Pyrazole-H),3.84(s,3H,OCH ₃ ),3.61(s,3H,N-CH ₃ ),2.39(s,3H,CH3).

Example 2:

Dissolve 10 mmol of compound IIIb in 30 mL of dichloromethane, then add 20 mmol of sodium acetate, and then add 13 mmol of intermediate II to it under ice-cooling conditions. After the addition was completed, the ice-bath reaction was continued for 22 hours. The reaction was stopped, and the reaction solution was rotary evaporated to dryness under reduced pressure, and the obtained residue was separated and purified by column chromatography to obtain the target compound Ib; ¹ H NMR (400MHz, CDCl ₃ ): δ8.62 (s, 1H, Pyrazine-H), 8.19(s, 1H, Pyrazine-H), 7.98(s, 1H, CH=N), 7.19～7.30(m, 2H, Ar-H), 7.04(s, 1H, Ar-H), 6.82～6.84( m,2H,Ar-H and Pyrazole-H),3.85(s,3H,OCH ₃ ),3.61(s,3H,N-CH ₃ ),2.39(s,3H,CH ₃ ).

Example 3:

2 mmol of compound IIIc was dissolved in 30 mL of dichloromethane, then 3 mL of triethylamine was added, and then 3 mmol of intermediate II was added thereto under ice-bath conditions. After addition, react at room temperature for 10 hours. The reaction was stopped, and the reaction solution was rotary evaporated to dryness under reduced pressure, and the obtained residue was separated and purified by column chromatography to obtain the target compound Ic. ¹ H NMR (400MHz, CDCl ₃ ) δ: 8.63(s, 1H, Pyrazine-H), 8.19(s, 1H, Pyrazine-H), 7.94(s, 1H, CH=N), 7.03(t, J= 8.4Hz, 2H, Ar-H), 6.84～6.87(m, 2H, Ar-H), 6.81(s, 1H, Pyrazole-H), 3.85(s, 3H, OCH ₃ ), 3.62(s, 3H, N-CH ₃ ), 2.37(s,3H,CH ₃ ).

Example 4:

3 mmol of compound IIId was dissolved in 30 mL of DMF, then 15 mmol of sodium carbonate was added, and then 4 mmol of intermediate II was added thereto under ice-cooling conditions. After the addition was completed, it was heated to 100°C and reacted for 13 hours. The reaction was stopped, and the reaction solution was rotary evaporated to dryness under reduced pressure, and the obtained residue was separated and purified by column chromatography to obtain the target compound Id. ¹ H NMR (400MHz, CDCl ₃ ) δ: 8.62(s, 1H, Pyrazine-H), 8.19(s, 1H, Pyrazine-H), 7.96(s, 1H, CH=N), 7.30(d, J= 8.8Hz, 2H, Ar-H), 6.82(d, J=10.0Hz, 3H, Ar-H and Pyrazole-H), 3.85(s, 3H, OCH ₃ ), 3.61(s, 3H, N-CH ₃ ),2.38(s,3H,CH ₃ ).

Example 5:

5 mmol of compound IIIe was dissolved in 30 mL of chloroform, then 20 mmol of pyridine was added, and then 5 mmol of intermediate II was added thereto under ice-cooling conditions. After addition, the reaction was heated to reflux for 18 hours. The reaction was stopped, and the reaction solution was rotary evaporated to dryness under reduced pressure, and the obtained residue was separated and purified by column chromatography to obtain the target compound Ie. ¹ H NMR (400MHz, CDCl ₃ ) δ: 8.63(s, 1H, Pyrazine-H), 8.19(s, 1H, Pyrazine-H), 7.97(s, 1H, CH=N), 7.20(d, J= 8.8Hz, 2H, Ar-H), 6.90(d, J＝8.8Hz, 2H, Ar-H), 6.81(s, 1H, Pyrazole-H), 3.84(s, 3H, OCH ₃ ), 3.62(s ,3H,N-CH ₃ ),2.38(s,3H,CH ₃ ).

Embodiment 6:

Dissolve 6 mmol of compound IIIf in 30 mL of tetrahydrofuran, then add 20 mmol of sodium bicarbonate, and then add 8 mmol of intermediate II to it under ice-bath conditions. After the addition was completed, the reaction was heated to reflux for 16 hours. The reaction was stopped, and the reaction solution was rotary evaporated to dryness under reduced pressure, and the obtained residue was separated and purified by column chromatography to obtain the target compound If. ¹ H NMR (400MHz, CDCl ₃ ) δ: 8.63(s, 1H, Pyrazine-H), 8.19(s, 1H, Pyrazine-H), 8.00(s, 1H, CH=N), 6.83(s, 1H, Pyrazole-H),6.43～6.65(m,3H,Ar-H),3.86(s,3H,OCH ₃ ),3.63(s,3H,N-CH ₃ ),2.39(s,3H,CH ₃ ).

Embodiment 7:

Screening of samples for insecticidal activity against armyworm

The leaf soaking method proposed by the International Resistance Action Committee (IRAC) was adopted: the target of the test was armyworm, that is, an appropriate amount of corn leaves were fully infiltrated in the prepared medicinal solution, dried naturally in the shade, put into a petri dish lined with filter paper, and inoculated. 10 mid-instar larvae of Armyworm larvae were cultured in an observation room at 24-27°C, and the results were observed after 2 days. Touch the insect body with a brush, and if there is no response, it is regarded as a dead insect. The test concentration is 1-500 μg/mL.

The results of the insecticidal activity test showed that all the compounds exhibited good activity against armyworms. When the test dose was 500 μg/mL (Table 1), the killing effects of compounds Ia-If on armyworm were 100%, 100%, 100%, 100%, 100% and 100%, respectively.

Table 1. Insecticidal activity data for Ia-If

The above experimental data show that the new compounds obtained by rationally combining the substituted pyrazole structural unit and the pyrazole oxime active unit all exhibit good biological activity. This type of compound can be used as an insecticidal lead for further structural derivation and Structure-activity relationship research. These experimental data also provide an important theoretical basis for continuing to engage in the molecular design, synthesis and biological activity research of new pyrazole oxime compounds in the future.

The basic principles, main features and advantages of the present invention have been shown and described above. Those skilled in the industry should understand that the present invention is not limited by the above-mentioned examples. What are described in the above-mentioned examples and descriptions are only to illustrate the principles of the present invention. The present invention also has various changes without departing from the spirit and scope of the present invention. These changes and improvements all fall within the scope of the claimed invention. The protection scope of the present invention is defined by the appended claims and their equivalents.

Claims (4)

1. the pyrazoles 9 oxime derivate I that one kind contains 1- (6- chloropyrazine -2- base) -3- methoxyl group pyrazoles unit, it is characterised in that structure Are as follows:

2. a kind of pyrazoles 9 oxime derivate for containing 1- (6- chloropyrazine -2- base) -3- methoxyl group pyrazoles unit as described in claim 1 The preparation method of I, it is characterised in that method is as follows:

3. a kind of pyrazoles 9 oxime derivate for containing 1- (6- chloropyrazine -2- base) -3- methoxyl group pyrazoles unit as described in claim 1 Purposes of the I in terms of preparing insecticide, it is characterised in that: the compound is used alone；Or used in a manner of Pesticidal combination, I.e. using compound I as active constituent, in addition insecticides adjuvant commonly used in the art is processed into aqueous emulsion, suspending agent, water dispersible granular Agent, missible oil.

4. a kind of pyrazoles 9 oxime derivate for containing 1- (6- chloropyrazine -2- base) -3- methoxyl group pyrazoles unit as claimed in claim 3 Purposes of the I in terms of preparing insecticide, it is characterised in that: when compound I is used as the active constituent in insecticide, in the desinsection Content in agent can be selected in the range of 0.1% to 99.5%.