Pyrazole amide derivative containing biphenyl fragment and bactericidal application thereof

Abstract

The invention discloses a pyrazole amide derivative containing a biphenyl fragment as shown in a formula I and application of the pyrazole amide derivative to prevention and treatment of plant diseases. The inhibition effect of the pyrazole amide derivative containing the biphenyl fragment on pathogenic bacteria such as apple black beancurd skin and the like is superior to that of an analogue fluxapyroxad. # imgabs0 #

Description

Technical Field

[0001] The invention belongs to the field of fungicides and relates to a pyrazoleamide derivative containing a biphenyl segment and application thereof in the preparation of fungicides resistant to pathogenic fungi such as apple black rot pathogen, rice sheath blight pathogen and rapeseed sclerotinia pathogen. Background Art

[0002] With the continued threat of agricultural diseases, chemical fungicides play an important role in crop protection. Apple black rot fungus (Valsa mali) is one of the main pathogenic fungi of apple and other fruit trees. The branch canker and fruit rot caused by it can lead to serious economic losses. At present, fungicides represented by succinate dehydrogenase inhibitors (SDHI) are widely used due to their high efficiency and broad-spectrum characteristics. Among them, flupyraclostrobin, as a representative of pyrazoleamide SDHI fungicides, exhibits significant inhibitory effects on a variety of pathogens by inhibiting the activity of complex II of the mitochondrial respiratory chain of pathogens. However, flupyraclostrobin is not ideal for apple black rot fungus. There are also few reports in the existing technology on the antibacterial activity of pyrazole compounds against apple black rot fungus.

[0003] In order to obtain pyrazole amide compounds with high antibacterial activity against apple black rot fungus, the present invention uses fluopyram as the parent structure and unexpectedly discovered a compound with high antibacterial activity against apple black rot fungus by migrating the terminal substituted phenyl group in fluopyram from the ortho position to the meta position and the para position. Summary of the Invention

[0004] The present invention aims to provide a pyrazoleamide derivative containing a biphenyl fragment having anti-plant pathogenic activity, wherein the compound is shown in Formula I:

[0005]

[0006] Among them, R 1 、R 2 、R 3 They may be the same or different and are selected from hydrogen, fluorine, chlorine, bromine and iodine.

[0007] The present invention provides the use of the pyrazole amide derivative containing a biphenyl fragment in preventing and treating plant diseases caused by fungi, wherein the pathogens are Coriolus solani, Rhizoctonia solani and Sclerotinia sclerotiorum. BRIEF DESCRIPTION OF THE DRAWINGS

[0008] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following briefly introduces the drawings required for describing the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. Those skilled in the art can also derive other drawings based on these drawings without inventive effort. Among them:

[0009] Figure 1 This is a comparison of the plate antibacterial effects of compounds I-1 and II in the examples of the present invention and a fungicide with a similar structure, fluopyram, on rice sheath blight and apple black rot fungus at a concentration of 20 mg / L. DETAILED DESCRIPTION

[0010] The present invention utilizes a phenyl migration strategy to design and synthesize a pyrazole amide derivative containing a biphenyl fragment, and finds that this type of compound has better antibacterial activity than fluopyram against pathogenic fungi such as apple black rot, and has the potential to be used as an active ingredient or synergistic ingredient in the development of new fungicides.

[0011] A pyrazole amide derivative containing a biphenyl fragment has the following molecular structural characteristics:

[0012]

[0013] Among them, R 1 、R 2 、R 3 They may be the same or different and are selected from hydrogen, fluorine, chlorine, bromine and iodine.

[0014] The specific embodiments of the present invention are further described below in conjunction with examples, but the present invention is not limited to the scope of the examples.

[0015] Example 1

[0016] Preparation of 3-(difluoromethyl)-1-methyl-N-(3',4',5'-trifluoro-[1,1'-biphenyl]-3-yl)-1H-pyrazole-4-carboxamide (I-1)

[0017]

[0018] In a pear-shaped flask, 0.85 g (5.0 mmol) of m-bromoaniline, 0.97 g (5.5 mmol) of p-trifluoromethylphenylboronic acid, a catalytic amount of tetrakis(triphenylphosphine)palladium, 1.38 g (10.0 mmol) of potassium carbonate, 25 mL of tetrahydrofuran and 12.5 mL of water were slowly added in sequence. The reaction was refluxed for 16 h. The reaction was monitored by TLC. The mixture was cooled to room temperature and the solvent was removed by rotary evaporation. The mixture was extracted with dichloromethane three times. The organic layers were combined and dried over anhydrous sodium sulfate. The intermediate 3',4',5'-trifluoro-[1,1'-biphenyl]-3-amine was obtained by column chromatography.

[0019] The intermediate 3',4',5'-trifluoro-[1,1'-biphenyl]-3-amine (0.45 g, 2.0 mmol) was added to the reaction flask and dissolved in 10 mL of dichloromethane. Triethylamine (0.61 g, 6.0 mmol) was then added. A solution of 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carbonyl chloride (0.47 g, 2.4 mmol) in 10 mL of dichloromethane was slowly added dropwise while stirring in an ice-water bath. The mixture was allowed to warm to room temperature and reacted for 5 hours. After completion of the reaction, the reaction solution was poured into 30 mL of water and extracted with dichloromethane (20 mL x 3). The organic layers were combined, washed with saturated sodium bicarbonate aqueous solution and saturated brine, dried over anhydrous sodium sulfate, and the dichloromethane was recovered by rotary evaporation. The residue was purified by column chromatography to yield compound I-1.

[0020] NMR data of compound I-1: 1 H NMR (400MHz, DMSO-d6) δ10.13(s,1H),8.51(s,1H),8.01(s,1H),7.71(d,J=7.4Hz ,1H),7.65–7.58(m,2H),7.48–7.40(m,2H),7.35(t,J=54.0Hz,1H),3.98(s,3H). 13 C NMR(101MHz,DMSO-d6)δ160.04,152.15–149.05(m),145.19(t,J=23.3Hz) ,139.51,137.54,137.06(d,J=16.3Hz),132.96,132.74(d,J=102.5Hz),13 2.04,131.50(d,J=9.7Hz),129.51,128.77(d,J=11.9Hz),122.18,119.23( d,J=166.7Hz),116.11,111.54–110.79(m),109.71(t,J=234.7Hz),39.46.

[0021] Example 2

[0022] Preparation of 3-(difluoromethyl)-1-methyl-N-(3',4',5'-trifluoro-[1,1'-biphenyl]-4-yl)-1H-pyrazole-4-carboxamide (Comparative Compound II)

[0023] The preparation method of comparative compound II is the same as the synthesis method of compound I-1.

[0024] NMR data of compound I-2: 1 H NMR(400MHz,Chloroform-d)δ8.25(s,1H),8.08(s,1H),7.68(d,J=8.2Hz,2H), 7.48(d,J=8.1Hz,2H),7.20–7.12(m,2H),6.91(t,J=54.2Hz,1H),3.96(s,3H). 13 C NMR(101MHz,Chloroform-d)δ177.48,159.49,152.63,150.30,142.59,138.12,136.3 1,134.40,127.59,120.67,117.04,112.22(t,J=232.8Hz),111.41–110.29(m),39.77.

[0025] Example 3

[0026] In vitro plate antibacterial activity test

[0027] This example is used to determine the in vitro antibacterial activity of the compound prepared in Example 1 against plant pathogenic fungi.

[0028] The plant pathogenic fungi tested were Valsa mali, Rhizoctonia solani and Sclerotonia sclerotiorum.

[0029] 1. Experimental Methods

[0030] The mycelial growth rate method was used. The target compound was weighed using a 1 / 100,000 analytical balance and dissolved in DMSO to prepare a mother solution with a concentration of 10 g / L. The mother solution was added to the PDA culture medium, and the target compound test concentration was 20 mg / L. Pure DMSO without the test compound was added to the PDA culture medium as a blank control, and the similar fungicide fluopyram was used as a positive control. A fresh fungus cake with a diameter of 5 mm was taken from the edge of the fungal colony cultured on the PDA, inoculated in the center of the above-mentioned PDA culture medium, and placed in an incubator for culture. The diameter (mm) of the fungus cake was measured with a vernier caliper using the cross-cross method, and the average value was calculated. The relative inhibition rate (%) was calculated according to the following formula:

[0031]

[0032] 2. Experimental Results

[0033] The results of the antibacterial activity test are shown in Table 1 and Figure 1 As shown, Example Compound I-1 exhibited high antibacterial activity against Aspergillus niger, Rhizoctonia solani, and Sclerotinia sclerotiorum, while Comparative Compound II exhibited significantly lower antibacterial activity. Clearly, Example Compound I-1 exhibited superior inhibitory activity against Aspergillus niger and Rhizoctonia solani at a concentration of 20 mg / L compared to the marketed fungicide, flupyraclostrobin.

[0034] Table 1

[0035]

[0036] The results of the antibacterial test showed that migrating the terminal benzene ring of the fungicide fluopyram to the meta position is expected to obtain more beneficial compounds against apple black rot pathogen and rice sheath blight pathogen.

Claims

1. A pyrazoleamide derivative containing a biphenyl fragment, characterized in that: The compound structure is shown in Formula I: Among them, R 1 、R 2 、R 3 They may be the same or different and are selected from hydrogen, fluorine, chlorine, bromine and iodine.

2. The use of the pyrazole amide derivative containing a biphenyl fragment according to claim 1, characterized in that Its application in preventing and controlling plant diseases caused by fungi.

3. The use of the pyrazole hydrazide derivative containing a phenylthiazole fragment in preventing and treating plant diseases caused by fungi according to claim 2, characterized in that The fungi are apple black rot pathogen, rice sheath blight pathogen and rapeseed sclerotinia pathogen.

4. A fungicide, comprising an active ingredient and excipients, wherein the active ingredient comprises the compound according to claim 1.

5. The bactericide according to claim 4, wherein The content of the active ingredient is 1 to 99.9% by weight.

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