CN1626520A - Compound in alpha (pyrazole formyloxy) acetanilide class of possessing fungicidal property - Google Patents

Abstract

An alpha-(pyrazole-formyl) acetylphenylamine compound with high bactericiding activity and its formula are disclosed.

Description

α - (pyrazole formyloxy) acetanilide compound with bactericidal activity

Technical Field

The invention belongs to the field of bactericides.

Background

Since fungicides or compositions thereof are resistant to pathogens after a period of use, there is a continuing need for new and improved fungicidal compounds and compositions. In addition, in consideration of economic and environmental aspects, it is also necessary to invent a bactericide which has a different action mechanism from the existing bactericide.

The preparation of certain α - (benzoyloxy) acetanilides has been reported (J.chem.Soc.Perkin II, 1977, 2028-containing 2032), but α - (pyrazolecarboxylato) acetanilides as shown in the present invention and their fungicidal activity have not been disclosed.

Disclosure of Invention

The invention provides an α - (pyrazole formyloxy) acetanilide compound with a novel structure, which is shown as a general formula (I):

wherein:

R₁is C₁-C₄Alkyl radical, C₂-C₆Alkenyl radical, C₂-C₆Alkynyl, benzyl or substituted benzyl;

R₂is C₁-C₆Alkyl or halo C₁-C₆An alkyl group;

R₃selected from H, halogen, nitro, C₁-C₄Haloalkyl or C₁-C₄An alkoxy group;

R₄、R₅are respectively selected from H or C₁-C₄An alkyl group;

R₆、R₇、R₈、R₉、R₁₀are respectively selected from H, halogen and C₁-C₃Alkyl, halo C₁-C₃Alkyl radical, C₁-C₃Alkoxy radical, C₃-C₆Cycloalkoxy, nitro or cyano;

and stereoisomers thereof.

Preferred compounds are of the general formula I:

R₁is C₁-C₄An alkyl group;

R₂is C₁-C₆An alkyl group;

R₃selected from halogens;

R₄、R₅are respectively selected from H;

R₆、R₇、R₈、R₉、R₁₀are respectively selected from H, halogen and C₁-C₃Alkyl, halo C₁-C₃Alkyl radical, C₁-C₃Alkoxy, nitro orA cyano group;

and stereoisomers thereof.

Further preferred compounds are those of the general formula I:

R₁is C₁-C₄An alkyl group;

R₂is C₁-C₆An alkyl group;

R₃is halogen;

R₄，R₅is selected from H;

R₆selected from H, halogen or nitro;

R₇、R₉selected from H, halogen, C₁-C₃Alkyl or C₁-C₃An alkoxy group;

R₈is H, halogen, C₁-C₃Alkyl, halo C₁-C₃Alkyl or nitro;

R₁₀is halogen; a nitro group; a cyano group;

and stereoisomers thereof.

The alkyl group referred to in the formula includes a straight chain or branched chain alkyl group. Haloalkyl refers to a group in which the alkyl group is substituted with one or more halogen atoms. Alkoxy means a straight chain or branched chain form, a group having an oxygen atom at the end, such as methoxy, ethoxy, n-propoxy, isopropoxy, and the like. Alkenyl refers to straight or branched chain forms having 1 to 2 carbon-carbon double bonds, such as vinyl, propenyl, allyl, and the like. Alkynyl refers to straight or branched chain forms having 1 to 2 carbon-carbon triple bonds, such as ethynyl, propynyl, propargyl, and the like. Halogen means fluorine, chlorine, bromine, iodine.

The compound (I) of the general formula of the present invention can be prepared by the following method:

the intermediate ketone (II) (which is commercially available) is reacted with diethyl oxalate, sodium methoxide or sodium ethoxide in a suitable solvent such as n-hexane, methanol, ethanol, benzene, toluene, ethyl acetate, THF or dioxane at-10 ℃ to boiling point for 0.5 to 48 hours to obtain compound (II-1).

The compound (II-1) is reacted with hydrazine hydrate (commercially available) in a suitable solvent at a temperature of from-10 ℃ to the boiling point for 0.5 to 48 hours to obtain the compound (II-2). The solvent can be chloroform, dichloromethane, carbon tetrachloride, hexane, benzene, toluene, ethyl acetate, DMF, THF or dioxane, etc.

Reacting the compound (II-2) with halogenated hydrocarbon such as dimethyl sulfate, diethyl sulfate or methyl iodide, benzyl chloride and the like in a proper solvent at the temperature of-10 ℃ to the boiling point for 0.5 to 48 hours to obtain a compound (II-3). The solvent can be chloroform, dichloromethane, carbon tetrachloride, hexane, benzene, toluene, ethyl acetate, acetone, DMF, THF or dioxane, etc. The addition of an alkali substance such as triethylamine, pyridine, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate or sodium bicarbonate is advantageous for the reaction.

The compound (II-3) reacts with chlorine, bromine, sulfuryl chloride, thionyl chloride or nitric acid and the like in a proper solvent at the temperature of-10 ℃ to the boiling point for 0.5 to 48 hours to obtain the compound (II-4). The solvent can be chloroform, dichloromethane, carbon tetrachloride, hexane, benzene, toluene, ethyl acetate, acetone, DMF, THF or dioxane, etc.

Reacting compound (II-4) with an alkali substance such as sodium hydroxide, potassium hydroxide, sodium carbonate or potassium carbonate in a suitable solvent such as water, ethyl acetate, acetone, DMF, THF or dioxane at-10 deg.C to boiling point for 0.5-48 hr to obtain compound (II-5).

Compound (II-5) is reacted with intermediate (II-6) in a suitable solvent such as chloroform, hexane, benzene, toluene, ethyl acetate, acetone, DMF, THF or dioxane at a temperature of-10 ℃ to boiling point for 0.5 to 48 hours to give compound (I). The addition of an alkali substance such as triethylamine, pyridine, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate or sodium bicarbonate is advantageous for the reaction.

The intermediate (II-6) can be prepared by reacting substituted aniline with 2-chloroalkyl acyl chloride in a suitable solvent at a temperature of-10 ℃ to the boiling point for 0.5-48 hours to obtain the compound (II-6). The solvent may be chloroform, dichloromethane, carbon tetrachloride, hexane, benzene, toluene, ethyl acetate, DMF, THF or dioxane. The addition of an alkali substance such as triethylamine, pyridine, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate or sodium bicarbonate is advantageous for the reaction.

Table 1: compounds of the invention partially represented by formula I

Compound R1 R2 R3 R4 R5 R6 R7 R8 R9 R10 mp(℃)
	1 CH3 C2H5 Cl H H H H Cl H H 158-160
2 CH3 C2H5 Cl H H Cl H H H H 159-160
	3 CH3 C2H5 Cl H H F H H H H 162-163
4 CH3 C2H5 Cl H H H H F H H 140-141
	5 CH3 C2H5 Cl H H H CH3 H H H 157-158
6 CH3 C2H5 Cl H H H H CH3 H H 155-156
	7 CH3 C2H5 Cl H H H Cl H H H 157-158
8 CH3 C2H5 Cl H H H CH3O H H H 146-147
	9 CH3 C2H5 Cl H H C2H5O H H H H 124-126
10 CH3 C2H5 Cl H H NO2 H F H H 129-131
	11 CH3 C2H5 Cl H H H H NO2 H H 156-158
12 CH3 C2H5 Cl H H Cl H Cl H H 150-151
	13 CH3 C2H5 Cl H H Cl Cl H H H 166-168
14 CH3 C2H5 Cl H H Cl H H Cl H 151-153
	15 CH3 C2H5 Cl H H H Cl Cl H H 132-134
16 CH3 C2H5 Cl CH3 H H H Cl H H 150-151
	17 CH3 C2H5 Cl CH3 H C2H5O H H H H 90-92
18 CH3 C2H5 Cl CH3 H H CH3 H H H 62-64
	19 CH3 C2H5 Cl CH3 H Cl Cl H H H 176-177
20 CH3 C2H5 Cl CH3 H Cl H Cl H H 168-169
	21 CH3 C2H5 H H H NO2 H H H H 98-100
22 CH3 C2H5 Br H H NO2 H H H H 110-120
	23 C2H5 C2H5 Cl H H NO2 H H H H 90-93
24 C2H5 C2H5 H H H NO2 H H H H 74-82
	25 C2H5 C2H5 Br H H H H Cl H H 140-152
26 C2H5 C2H5 Cl H H H H Cl H H 82-86
	27 C2H5 C2H5 Br H H NO2 H H H H 100-103
28 4-Cl-C6H4CH2 C2H5 H H H NO2 H H H H 98-102
	29 4-Cl-C6H4CH2 C2H5 Cl H H NO2HHHHH oil
30 C6H5CH2 C2H5HHHHHHclHH oil
	31 C6H5 C2H5 Cl H H NO2 H H H H 68-72
32 C6H5 C2H5Cl H H H Cl H oil
	33 C6H5 C2H5 H H H NO2HHHHH oil

34 HC*CCH2 C2H5 H H H NO2HHHHH oil
	35 CH3 C2H5 Cl H H H NO2 H H H 108-112
36 CH3 C2H5 Cl H H NO2 H Cl H H 120-122
	37 CH3 C2H5 Cl H H NO2 H CF3 H H 134-138
38 CH3 C2H5 Cl H H NO2Hcl H Cl oil
	39 CH3 C2H5 Cl H H H NO2 Cl H H 138-141
40 CH3 C2H5 Cl H H NO2 H CH3 H H 136-138
	41 CH3 CH3 Cl H H NO2 H H H H 136-138
42 CH3 C2H5 Cl H H NO2 H H Cl H 138-147
	43 CH3 C2H5 Cl H H NO2 H OCH3H H oil
44 CH3 CH3 Cl H H NO2 H Cl H H 128-139
	45 CH3 CH3 Cl H H NO2 H CH3 H H 176-179
46 CH3 CH3 Cl H H NO2 H F H H 164-170
	47 CH3 CH3 Cl H H NO2 H Cl H Cl 185-192
48 CH3 C2H5 Cl H H NO2 H H H H 118-120

Note: HC-CCH₂Is propargyl

Of some of the compounds in Table 1¹H NMR(300MHz，CDCl₃) The data are as follows:

compound 29: 8.870-8.266ppm (dxd, 1H), 8.261-8.233ppm (d, 1H), 7.714-7.661ppm (t, 1H), 7.373-7.345ppm (d, 1H), 7.272-7.199ppm (m, 4H), 5.407ppm (s, 2H), 5.059ppm (s, 2H), 4.352ppm (s, 1H), 2.687-2.661ppm (q, 2H), 1.058-1.008ppm (t, 3H)

Compound 30: 7.521-7.491ppm (d, 2H), 7.358-7.334ppm (d, 2H), 7.285-7.121ppm (m, 5H), 6.768ppm (s, 1H), 5.412ppm (s, 2H), 4.942ppm (s, 2H), 2.589-2.566ppm (q, 2H), 1.271-1.220ppm (t, 3H)

Compound 32: 8.500ppm (s, 1H), 7.516-7.487ppm (d, 2H), 7.327-7.241ppm (m, 7H), 5.713ppm (s, 2H), 4.865ppm (s, 2H), 2.752-2.702ppm (q, 2H), 1.338-1.288ppm (t, 3H)

Compound 33: 11.200ppm (s, 1H), 8.870-8.266ppm (dxd, 1H), 8.261-8.233ppm (d, 1H), 7.714-7.661ppm (t, 1H), 7.287-7.235ppm (m, 5H), 7.134ppm (s, 1H), 5.749ppm (s, 2H), 4.901ppm (s, 1H), 2.787-2.761ppm (q, 2H), 1.357-1.306ppm (t, 3H)

Compound 34: 11.232ppm (s, 1H), 8.878-8.845ppm (dxd, 1H), 8.289-8.256ppm (d, 1H), 7.714ppm (t, 1H), 7.298-7.246(d, 1H), 7.135ppm (s, 1H), 5.345-5.336ppm (s, 2H), 4.975ppm (s, 2H), 2.785-2.710ppm (q, 2H), 2.380-2.371ppm (t, 1H), 1.340-1.289ppm (t, 3H)

Compound 38: 8.800ppm (s, 1H), 7.925-7.916ppm (d, 1H), 7.751-7.743ppm (d, 1H), 4.982ppm (s, 2H), 4.156ppm (s, 3H), 2.694-2.643ppm (q, 2H), 1.320-1.269ppm (t, 3H)

Compound 43: 10.500ppm (s, 1H), 8.8.590-8.570ppm (d, 1H), 7.650-7.630ppm (d, 1H), 7.262ppm (d, 1H), 5.011ppm (s, 2H), 4.143ppm (s, 3H), 3.871ppm (s, 3H), 2.697-2.671ppm (q, 2H), 1.294-1.243ppm (t, 3H)

The compounds of the general formula (I) according to the invention have fungicidal activity, for example against diseases of the class Phycomycetes, in particular downy mildew.

The invention also discloses a bactericidal composition taking the compound in the general formula (I) as an active component. The weight percentage of the active components in the bactericidal composition is between 1 and 99 percent. The bactericidal composition also comprises an agriculturally acceptable carrier.

A further embodiment of the invention is a method of controlling diseases which comprises applying the fungicidal composition of the invention to a disease growth medium, such as a plant, in need of disease control. Preferably, an effective amount of from 10 grams per hectare to 5000 grams per hectare is generally selected, with an effective amount of from 50 grams per hectare to 3000 grams per hectare being preferred.

The compounds of the invention may be applied to the foliage in the form of a formulation. Such compounds are typically dissolved in a carrier or formulated so as to be more easily dispersible when used as a bactericide. For example: these chemicals can be formulated as wettable powders or emulsifiable concentrates. In these compositions, at least one liquid or solid carrier is added and, when desired, suitable surfactants can be incorporated.

The third embodiment of the present invention is therefore the use of a composition comprising as active ingredient a compound of formula (I) for controlling plant diseases.

For certain applications, one or more additional antimicrobial agents may be added to the antimicrobial compositions of the present invention, thereby providing additional advantages and benefits.

The compounds of the present invention can be used alone or in combination with other known insecticides, herbicides, plant growth regulators,fertilizers, or the like.

It should be understood that various changes and modifications may be made within the scope of the present invention as defined by the claims.

Detailed Description

The following examples, biological test results, are provided to further illustrate the invention and are not meant to limit the invention.

Synthesis examples

Synthesis of compound 41 in table 1:

A1 A2 B1

a1(15 g, 0.259 mol), sodium methoxide (58 g, 28%, 0.300 mol) and 100 ml of absolute methanol were added to a 500 ml reaction flask, and a 50 ml methanol solution of A2(36.7 g, 0.251 mol) was added dropwise with stirring in a water bath, after 4 hours, the water bath was removed, and the reaction was continued at room temperature for 2 hours. 200 ml of water and 200 ml of dichloromethane were added to the reaction mixture under ice water cooling, followed by adjusting the pH to 3 with concentrated hydrochloric acid, separation of the layers, extraction of the aqueous layer with 200 ml of dichloromethane, combination of the organic layers, washing of the organic layer with 200 ml of saturated aqueous sodium chloride solution, drying over anhydrous magnesium sulfate, and desolventizing under reduced pressure to give 24 g of yellow oily substance B1.

A250 ml reaction flask was charged with hydrazine hydrate (10.5 g, 80%, 0.168 mol) and 30 ml of toluene, and a solution of B1(24 g, 0.150 mol) in 80 ml of toluene was added dropwise over 40 minutes with stirring in an ice water bath. After 4 hours of reaction in a water bath, 200 ml of ethyl acetate and 200 ml of water were added, the layers were separated, and the organic layer was washed with 200 ml of saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and desolventized under reduced pressure to give 19.6 g of oil C.

A250 ml reaction flask was charged with C (19.6 g, 0.130 mol) and 100 ml of dichloromethane, and a solution of dimethyl sulfate (17.6 g, 0.14 mol) in 50 ml of dichloromethane was added dropwise with stirring at room temperature for 30 minutes, and the temperature was raised to 40%℃After reacting for 4 hours, cooling to room temperature, adding 150 ml of water, separating layers, washing an organic layer with 200 ml of saturated sodium bicarbonate and 200 ml of saturated sodium chloride aqueous solution, drying with anhydrous magnesium sulfate, and removing solvent under reduced pressure to obtain 22 g of oily matter D.

D (22 g, 0.130 mol) and 100 ml of dichloromethane are added into a 250 ml reaction bottle, 50 ml of dichloromethane solution of sulfonyl chloride (21.5 g, 0.160 mol) is dropwise added under stirring at room temperature, after 50 minutes of dropwise addition, reaction is continued for 5 hours, and the reaction solution is washed by 300 ml of water, 300 ml of saturated sodium bicarbonate and 200 ml of saturated aqueous sodium chloride solution, dried by anhydrous magnesium sulfate and desolventized under reduced pressure to obtain 22 g of oily matter E.

E (22 g, 0.126 mol), sodium hydroxide (6 g, 0.15 mol) and 100 ml of water are added into a 250 ml reaction bottle, the mixture is heated to 40 ℃ for reaction for 4 hours, the PH value is adjusted to be 2 by hydrochloric acid under the cooling of a water bath, solid is separated out, the solid is filtered, a filter cake is washed by 20 ml of water, and the filter cake is naturally dried by air to obtain white solid F, and the weight of the white solid F is 16.5 g.

Adding F (0.5 g, 2.8 mmol), F1(0.6 g, 2.7 mmol), potassium carbonate (0.43 g, 3 mmol) and 10 ml of DMF (anhydrous) into a 50 ml reaction bottle, heating to 40-50 ℃ under stirring for reaction for 5 hours, after the reaction is finished, cooling the reaction liquid to room temperature, adding 50 ml of water, precipitating a solid, filtering, washing a filter cake with 10 ml of water, and naturally drying in the air to obtain 0.6 g of a gray solid, namely the compound 41.

The other compounds in table 1 can be prepared by similar methods as above.

Example of bioassay:

1. test materials

Test samples were weighed and dissolved in acetone (acetone: liquid medicine: 9: 1), and water containing 0.1% tween 80 was added to prepare 10 ml of liquid medicine of a desired concentration. And (3) carrying out hand-held sprayer, and spraying the liquid medicine on the cucumber seedlings in the two-leaf one-heart period, wherein the liquid spraying amount is 2 ml/treatment. The treated test material was air-dried naturally, and after 24 hours, 5X 10 cells were inoculated with an inoculator⁵Spraying the cucumber downy mildew sporangium suspension per milliliter on the back of the cucumber slice until the leaves are soaked in water. Then, the mixture was incubated in a humid chamber (temperature: 24 ℃, RH 100%, 12 hours light), and the bacteriostatic activity of the compound was investigated after 4 days.

The survey results are given by the nine grades 100, 99, 95, 90, 95, 80, 70, 50, 0, with the "100" grade representing no disease and the "0" grade representing the most severe degree of disease:

100: no visible symptoms;

99: the infected points or halos of the germs can be seen on the leaves, but no scab exists;

95: the number of the disease spots on the leaves is 1-2;

90: the number of the disease spots on the leaves is 3-5;

85: the number of the disease spots on the leaves is 6-10;

80: the number of the disease spots on the leaves is 11-15;

70: the number of the disease spots on the leaves is 16-25;

50: the number of the scabs on the leaves is 26-50;

0: the number of the scab on the leaf is more than 50.

2. Test results

Table 2: fungicidal Activity of part of the Compounds of formula I (dose 200ppm)

Compound (I)	Downy mildew inhibition rate
		Compound 2	70
Compound 3	70
		Compound 5	95
Compound 7	50
		Compound 9	90
Compound 10	100
		Compound 11	100
Compound 12	100
		Compound 14	90
Compound 17	100
		Compound 22	100
Compound 26	70
		Compound 29	70
Compound 31	70
		Compound 36	98
Compound 37	85
		Compound 38	99
Compound 40	100
		Compound 41	99
Compound 42	99
		Compound 48	100

Claims (6)

1.α - (pyrazole formyloxy) acetanilide compound is shown as a general formula (I):

wherein:

R₁is selected from C₁-C₄Alkyl radical, C₂-C₆Alkenyl radical, C₂-C₆Alkynyl, benzyl or substituted benzyl;

R₂is selected from C₁-C₆Alkyl or halo C₁-C₆An alkyl group;

R₃selected from H, halogen, nitro, C₁-C₄Haloalkyl or C₁-C₄An alkoxy group;

R₄、R₅are respectively selected from H or C₁-C₄An alkyl group;

R₆、R₇、R₈、R₉、R₁₀are respectively selected from H, halogen and C₁-C₃Alkyl, halo C₁-C₃Alkyl radical, C₁-C₃Alkoxy radical, C₃-C₆Cycloalkoxy, nitro or cyano;

and stereoisomers thereof.

2. The compound according to claim 1, wherein:

R₁is C₁-C₄An alkyl group;

R₂is C₁-C₆An alkyl group;

R₃selected from halogens;

R₄、R₅are respectively selected from H;

R₆、R₇、R₈、R₉、R₁₀are respectively selected from H, halogen and C₁-C₃Alkyl, haloC₁-C₃Alkyl radical, C₁-C₃Alkoxy, nitro or cyano;

and stereoisomers thereof.

3. The compound of claim 2, wherein:

R₁is C₁-C₄An alkyl group;

R₂is C₁-C₆An alkyl group;

R₃is halogen;

R₄，R₅is selected from H;

R₆selected from H, halogen or nitro;

R₇、R₉selected from H, halogen, C₁-C₃Alkyl or C₁-C₃An alkoxy group;

R₈is H, halogen, C₁-C₃Alkyl, halo C₁-C₃Alkyl or nitro;

R₁₀is halogen; a nitro group; a cyano group;

and stereoisomers thereof.

4. A bactericidal composition contains an active component of a compound shown as a general formula (I) and an agriculturally acceptable carrier, wherein the weight percentage of the active component in the composition is 1-99%.

5. Use of the compound of claim 1 or a composition thereof for controlling plant diseases.

6. A method of controlling plant disease comprising applying the composition of claim 4 to a plant in need of disease control at an effective dose of from 50 grams per hectare to 3000 grams per hectare.