Preparation method and application of myrtenyl-1, 3, 4-oxadiazole formyl hydrazine compound

Abstract

The invention discloses a preparation method of a myrtenyl-1, 3, 4-oxadiazole formyl hydrazine compound as well as a product and application of the myrtenyl-1, 3, 4-oxadiazole formyl hydrazine compound. The preparation method comprises the following steps: oxidizing myrtenal to synthesize myrtenic acid; reacting the myrtenic acid with hydrazine hydrate to generate myrtenyl hydrazide; the preparation method comprises the following steps: reacting myrtenyl hydrazide with methyl oxalyl chloride to generate myrtenyl-1, 3, 4-oxadiazole methyl ester; the preparation method comprises the following steps: reacting myrtenyl-1, 3, 4-oxadiazole methyl ester with each substituted phenylhydrazine to synthesize a myrtenyl-1, 3, 4-oxadiazole formyl hydrazine compound; the compound has a general formula I: # imgabs0 #, wherein R is H, 4-F, 4-Cl, 4-Br, 4-I, 4-CH3, 2-CH3, 2-F, 3-F, 2-Cl, 3-Cl, 2-Br, 3-Br and 4-OCH3; the compound has a good prevention effect on sclerotinia sclerotiorum, botryosphaeria dothidea and fusarium graminearum under an in-vitro condition, and can be used for preventing and treating fungal diseases of agricultural or forestry plants. The preparation method of the compound is simple and convenient, the yield is high, and the product property is stable.

Description

Technical Field

[0001] The invention belongs to the technical field of pesticide synthesis, and specifically relates to a preparation method and application of myrtenyl-1,3,4-oxadiazolecarboxylic acid hydrazide compounds. Background Art

[0002] Crop diseases and insect pests are one of the important constraints affecting the sustainable and healthy development of agricultural products and forest resources. Pesticides, as a special commodity for controlling biological hazards such as diseases and insect pests of agricultural and forestry crops, play an extremely important role in protecting the normal growth of agricultural and forestry crops, improving agricultural production, and promoting food security.

[0003] At present, the long-term use of a single type of pesticide will also cause plant pathogens, pests and weeds to develop resistance. Therefore, the development of new types of pesticides with targeted effects is crucial to the effective control of plant diseases.

[0004] So far, there has been no report on the use of myrtenyl-1,3,4-oxadiazolecarboxylic acid hydrazide compounds as agricultural fungicides. Summary of the invention

[0005] The purpose of this section is to summarize some aspects of embodiments of the present invention and briefly introduce some preferred embodiments. Some simplifications or omissions may be made in this section and the specification abstract and the invention title of this application to avoid blurring the purpose of this section, the specification abstract and the invention title, and such simplifications or omissions cannot be used to limit the scope of the present invention.

[0006] In view of the above problems and / or the problems existing in the prior art, the present invention is proposed.

[0007] Therefore, the purpose of the present invention is to overcome the deficiencies in the prior art and provide a class of myrtenyl-1,3,4-oxadiazolecarboxylic acid hydrazide compounds.

[0008] In order to solve the above technical problems, the present invention provides the following technical solution: a class of myrtle-1,3,4-oxadiazolecarboxylic acid hydrazide compounds, the structural formula of the myrtle-1,3,4-oxadiazolecarboxylic acid hydrazide compounds is as follows:

[0009]

[0010] Among them, the R group is selected from one of 4-H, 4-F, 4-Cl, 4-Br, 4-I, 4-CH3, 2-CH3, 2-F, 3-F, 2-Cl, 3-Cl, 2-Br, 3-Br, and 3-O-CH3.

[0011] Another object of the present invention is to overcome the deficiencies in the prior art and provide a method for preparing a class of myrtenyl-1,3,4-oxadiazolecarboxylic acid hydrazide compounds, comprising:

[0012] Myrtenal was oxidized to synthesize myrtenic acid;

[0013] reacting myrtenic acid with hydrazine hydrate to form myrtenyl hydrazide;

[0014] Myrtenyl hydrazide is reacted with methyl oxalyl chloride to produce myrtenyl-1,3,4-oxadiazole methyl ester;

[0015] Myrtenyl-1,3,4-oxadiazole methyl ester is reacted with substituted phenylhydrazine to prepare myrtenyl-1,3,4-oxadiazole carboxylic acid hydrazide compounds.

[0016] As a preferred embodiment of the preparation method of the present invention, the synthetic myrtle acid comprises:

[0017] Dissolve myrtle aldehyde in acetonitrile, dissolve potassium dihydrogen phosphate in water, mix the two in a single-necked flask under ice bath conditions, add 30% hydrogen peroxide and PEG-400, dissolve sodium chlorite in water, slowly drop sodium chlorite aqueous solution using a 50 ml constant pressure funnel, react for 18 hours, and detect by TLC. After the reaction is complete, add sodium sulfite, rotate and concentrate to remove acetonitrile, add ethyl acetate for extraction, combine the organic layers, wash with saturated brine, dry with anhydrous sodium sulfate, and rotate and concentrate to obtain the target compound oily myrtle acid;

[0018] Wherein, the molar ratio of myrtle aldehyde, potassium dihydrogen phosphate, hydrogen peroxide, PEG-400, sodium chlorite and sodium sulfite is 1:0.25:1.1:0.14:1.3:0.07.

[0019] As a preferred embodiment of the preparation method of the present invention, wherein: the synthesis of myrtle hydrazide comprises:

[0020] Dissolve myrtle acid in anhydrous dichloromethane, then add DMAP and EDCI, add 85% hydrazine hydrate dropwise in an ice bath, remove the ice bath after the addition, detect that the raw material reaction is complete by TLC, evaporate and concentrate to remove dichloromethane, add ethyl acetate for extraction, combine the organic layers, wash with saturated brine, dry with anhydrous sodium sulfate, and rotary concentrate to obtain a crude myrtle hydrazide, separate and purify with 200-300 mesh silica gel column chromatography, and purify with a petroleum ether / ethyl acetate volume ratio of 10:1 to 3:1 to obtain the target compound myrtle hydrazide;

[0021] Wherein, the molar ratio of myrtle acid, DMAP, EDCI and hydrazine hydrate is 1:0.1:1.2:2.

[0022] As a preferred embodiment of the preparation method of the present invention, the synthesis of myrtenyl-1,3,4-oxadiazole methyl ester comprises:

[0023] Dissolve myrtenyl hydrazide in phosphorus oxychloride, add methyl oxalyl chloride dropwise in an ice bath, reflux at 85°C, react for 2 to 3 hours, pour the reaction solution into ice water and stir, add ethyl acetate for extraction, combine the organic layers, wash with saturated sodium bicarbonate, dry with anhydrous sodium sulfate, and concentrate by rotary centrifugation to obtain a crude product of myrtenyl-1,3,4-oxadiazole methyl ester, separate and purify by 200-300 mesh silica gel column chromatography, and purify by petroleum ether / ethyl acetate volume ratio of 200:1 to 50:1 to obtain the target compound myrtenyl-1,3,4-oxadiazole methyl ester;

[0024] Wherein, the molar ratio of myrtle hydrazide to methyl oxalyl chloride is 1:1.5.

[0025] As a preferred embodiment of the preparation method of the present invention, wherein: the synthesis of myrtenyl-1,3,4-oxadiazolecarboxylic acid hydrazide comprises:

[0026] Dissolve myrtenyl-1,3,4-oxadiazole methyl ester in anhydrous DMF in a pressure tube, add substituted phenylhydrazine, heat to 100°C and react for 48 hours, then stop the reaction, remove the solvent, add ethyl acetate for extraction, combine the organic layers, wash with saturated brine, dry with anhydrous sodium sulfate, and rotary concentrate to obtain myrtenyl-1,3,4-oxadiazole carboxylic acid hydrazide of each substituent, separate and purify with 200-300 mesh silica gel column chromatography, and purify with petroleum ether / ethyl acetate volume ratio of 200:1 to 20:1 to obtain myrtenyl-1,3,4-oxadiazole carboxylic acid hydrazide of the target compound substituent;

[0027] Wherein, the molar ratio of the myrtenyl-1,3,4-oxadiazole methyl ester to each substituted phenylhydrazine is 1:2.5.

[0028] As a preferred embodiment of the preparation method of the present invention, the substituted phenylhydrazine includes phenylhydrazine, 4-fluorophenylhydrazine, 4-chlorophenylhydrazine, 4-bromophenylhydrazine, 4-iodophenylhydrazine, 4-methylphenylhydrazine, 2-methylphenylhydrazine, 2-fluorophenylhydrazine, 3-fluorophenylhydrazine, 2-chlorophenylhydrazine, 3-chlorophenylhydrazine, 2-bromophenylhydrazine, 3-bromophenylhydrazine, and 4-methoxyphenylhydrazine.

[0029] Another object of the present invention is to overcome the deficiencies in the prior art and provide the use of myrtenyl-1,3,4-oxadiazolecarboxylic acid hydrazide compounds in preventing and controlling plant fungi in agriculture or forestry, wherein: the plant fungi include grape sclerotinia, rapeseed sclerotinia, tomato gray mold, potato infestation and pepper Phytophthora.

[0030] Beneficial effects of the present invention:

[0031] (1) The compounds described in the present invention are myrtenyl-1,3,4-oxadiazole carboxylic acid hydrazide derivatives, which have novel molecular structures and are all new compounds with distinct chemical structure characteristics. The structural formula contains myrtenyl, oxadiazole group and hydrazide. The preparation method of the compounds described in the present invention is simple, the raw materials are easily available, and the reaction conditions are mild and easy to control.

[0032] (2) The compound of the present invention is an agent for controlling plant fungi in the field of agriculture or forestry, and the agent shows good effects in controlling grape sclerotinia, rapeseed sclerotinia, tomato gray mold, potato late blight and pepper phytophthora. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] 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. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative labor. Among them:

[0034] Figure 1 Schematic diagram of the preparation method of myrtenyl-1,3,4-oxadiazolecarboxylic acid hydrazide compounds in an embodiment of the present invention.

[0035] Figure 2 This is a graph showing the in vitro antifungal test of I-4 at different concentrations against Botrytis cinerea and Gibberella fusca in the example of the present invention.

[0036] Figure 3 This is a graph showing the protection and treatment experiment of I-4 at 100 mg / L and 200 mg / L on apple fruit infected with Botrytis cinerea. DETAILED DESCRIPTION

[0037] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the specific implementation methods of the present invention are described in detail below in conjunction with the embodiments of the specification.

[0038] In the following description, many specific details are set forth to facilitate a full understanding of the present invention, but the present invention may also be implemented in other ways different from those described herein, and those skilled in the art may make similar generalizations without violating the connotation of the present invention. Therefore, the present invention is not limited to the specific embodiments disclosed below.

[0039] Secondly, the term "one embodiment" or "embodiment" as used herein refers to a specific feature, structure, or characteristic that may be included in at least one implementation of the present invention. The term "in one embodiment" that appears in different places in this specification does not necessarily refer to the same embodiment, nor does it refer to a separate or selective embodiment that is mutually exclusive with other embodiments.

[0040] The schematic diagram of the preparation method of myrtenyl-1,3,4-oxadiazole carboxylic acid hydrazide compounds of the present invention is shown in Figure 1 , including the following steps:

[0041] (1) myrtle aldehyde (purchased from Anaiji Chemical Mall, CAS No. 18486-69-6) is oxidized to synthesize myrtle acid;

[0042] (2) reacting myrtle acid with hydrazine hydrate to generate myrtle hydrazide;

[0043] (3) reacting myrtenyl hydrazide with methyl oxalyl chloride to generate myrtenyl-1,3,4-oxadiazole methyl ester;

[0044] (4) Myrtenyl-1,3,4-oxadiazole methyl ester is reacted with each substituted phenylhydrazine to prepare myrtenyl-1,3,4-oxadiazole carboxylic acid hydrazide compounds.

[0045] The specific steps are:

[0046] (1) Preparation of myrtle acid (II)

[0047] Take myrtle aldehyde (500 mg, 3.3 mmol) and dissolve it in 5 ml of acetonitrile, take potassium dihydrogen phosphate (391 mg, 4.3 mmol) and dissolve it in 3 ml of water, mix the two in a 150 ml single-necked flask under ice bath conditions, add 30% hydrogen peroxide (300 ul, 3.6 mmol) and PEG-400 (190 mg, 0.5 mmol), take sodium chlorite (391 mg, 4.3 mmol) and dissolve it in 7 ml of water, slowly add sodium chlorite aqueous solution dropwise with a 50 ml constant pressure funnel, react for 18 h, and detect by TLC. After the reaction is complete, add sodium sulfite (32 mg, 0.26 mmol), and concentrate by rotary concentrator to remove acetonitrile. Add ethyl acetate for extraction, combine the organic layers, wash with saturated brine, dry over anhydrous sodium sulfate, and concentrate by rotary concentrator to obtain 450 mg of myrtle acid as an oil;

[0048] 1H NMR(600MHz,Chloroform-d)δ6.99(tt,J=3.2,1.5Hz,1H),2.78(td,J=5.7,1.6Hz,1H),2.51–2.4 7(m,1H),2.47–2.39(m,2H),2.15–2.12(m,1H),1.34(s,3H),1.12(d,J=9.1Hz,1H),0.79(s,3H). 13 C NMR(150MHz,Chloroform-d)δ171.37,139.76,139.61,41.02,40.35,37.83,32.51,31.40,25.98,21.07.MS ESI m / z:calcd for C 10 H 14 O2Na[M+Na]+:189.0891; found 189.0892.

[0049] (2) Preparation of myrtle hydrazide (III)

[0050] Dissolve myrtle acid (500 mg, 3 mmol) in 8 ml of anhydrous dichloromethane, then add DMAP (36 mg, 0.3 mmol) and EDCI (689 mg, 4.2 mmol), add 85% hydrazine hydrate (241 mg, 6 mmol) dropwise under ice bath, remove the ice bath after addition, detect that the raw material reaction is complete by TLC, evaporate and concentrate to remove dichloromethane, add ethyl acetate to extract, combine the organic layers, wash with saturated brine, dry with anhydrous sodium sulfate, and rotary concentrate to obtain crude myrtle hydrazide, separate and purify by 200-300 mesh silica gel column chromatography, purify by petroleum ether / ethyl acetate volume ratio of 10:1 to 3:1, and obtain 410 mg of the target compound myrtle hydrazide;

[0051] 1 H NMR(600MHz,Chloroform-d)δ6.40(tt,J=3.1,1.5Hz,1H),3.65(s,2H),2.60(td,J=5.6,1.6Hz,1H),2. 49–2.45(m,1H),2.43–2.34(m,2H),2.15–2.12(m,1H),1.33(s,3H),1.15(d,J=9.1Hz,1H),0.82(s,3H). 13 C NMR(150MHz,Chloroform-d)δ168.40,141.98,130.23,41.92,40.54,37.92,31.95,31.49,26.04,21.07.MS ESI m / z:calcd for C10 H 17 N2O[M+H]+:181.1341; found181.1339.

[0052] (3) Preparation of 1,3,4-oxadiazole methyl ester (IV)

[0053] Dissolve myrtenyl hydrazide (1 g, 3.7 mmol) in 10 ml of phosphorus oxychloride, add methyl oxalyl chloride (690 mg, 5.6 mmol) dropwise in an ice bath, reflux at 85°C, react for 2 to 3 hours, pour the reaction solution into ice water and stir, add ethyl acetate for extraction, combine the organic layers, wash with saturated sodium bicarbonate, dry with anhydrous sodium sulfate, and concentrate by rotary concentration to obtain a crude product of myrtenyl-1,3,4-oxadiazole methyl ester, separate and purify by 200-300 mesh silica gel column chromatography, and purify by petroleum ether / ethyl acetate volume ratio of 200:1 to 50:1 to obtain 700 mg of the target compound myrtenyl-1,3,4-oxadiazole methyl ester.

[0054] 1 H NMR(600MHz,Chloroform-d)δ6.89(tt,J=3.3,1.5Hz,1H),4.04(s,3H),3.12–3.09(m,1H),2.61–2.58(m,1H),2.58–2.56 (m,1H),2.52(dt,J=20.0,3.1Hz,1H),2.22(ttd,J=6.0,2.9,1.3Hz,1H),1.39(s,3H),1.27(d,J=9.3Hz,1H),0.85(s,3H). 13 C NMR(150MHz,Chloroform-d)δ165.92,155.78,155.06,134.47,132.34,53.76,42.11,40.29,38.06,32.62,31.32,25.83,20.98.MS ESI m / z:calcd for C 13 H 16 N2O3Na[M+Na]+:271.1059; found 271.1063.

[0055] (4) Preparation of substituted myrtenyl-1,3,4-oxadiazole carboxylic acid hydrazide derivatives (I)

[0056] Dissolve myrtenyl-1,3,4-oxadiazole methyl ester (500 mg, 2 mmol) in 5 ml of anhydrous DMF in a 15 ml pressure tube, add each substituent phenylhydrazine (5 mmol), heat to 100°C and react for 48 hours, then stop the reaction, remove the solvent, add ethyl acetate for extraction, combine the organic layers, wash with saturated brine, dry with anhydrous sodium sulfate, and concentrate by rotary concentration to obtain myrtenyl-1,3,4-oxadiazole hydrazide of each substituent, separate and purify by 200-300 mesh silica gel column chromatography, and purify by petroleum ether / ethyl acetate volume ratio of 200:1 to 20:1 to obtain the target compound substituent myrtenyl-1,3,4-oxadiazole hydrazide.

[0057] Example 1

[0058] Prepare myrtenyl-1,3,4-oxadiazolecarboxylic acid hydrazide derivative (I-1):

[0059]

[0060] Dissolve myrtenyl-1,3,4-oxadiazole methyl ester (500 mg, 2 mmol) in 5 ml of anhydrous DMF in a 15 ml pressure tube, add phenylhydrazine (540 mg, 5 mmol), heat to 100 ° C and react for 48 hours, stop the reaction, remove the solvent, add ethyl acetate for extraction, combine the organic layers, wash with saturated brine, dry with anhydrous sodium sulfate, and rotary concentrate to obtain a crude product, which is separated and purified by 200-300 mesh silica gel column chromatography, and purified by petroleum ether / ethyl acetate volume ratio of 200:1 to 20:1 to obtain the target compound myrtenyl-1,3,4-oxadiazole carboxylic acid hydrazide derivative (Ⅰ-1). White solid; yield, 30.5%.

[0061] White solid; Yield: 30.5%; 1 H NMR(600MHz,Chloroform-d)δ9.11(s,1H),7.25–7.21(m,2H),6.94(tt,J=7.4,1.1Hz,1H),6.90(d,J=1.2Hz,1H),6.88–6.87(m,2H),3 .08(td,J=5.6,1.5Hz,1H),2.60–2.57(m,1H),2.57–2.48(m,2H),2.24–2.22(m,1H),1.39(s,3H),1.26(d,J=9.3Hz,1H),0.85(s,3H). 13CNMR(151MHz,Chloroform-d)δ166.05,156.70,153.80,146.71,134.47,132.0 3,129.29,121.89,113.84,42.07,40.20,37.99,32.54,31.23,25.77,20.91.MS ESI m / z:calcd for C 18 H 21 N4O2[M+H]+:325.1665; found325.1660.

[0062] Example 2

[0063] Prepare myrtenyl-1,3,4-oxadiazolecarboxylic acid hydrazide derivative (I-2):

[0064]

[0065] Dissolve myrtenyl-1,3,4-oxadiazole methyl ester (500 mg, 2 mmol) in 5 ml of anhydrous DMF in a 15 ml pressure tube, add 4-fluorophenylhydrazine (630 mg, 5 mmol), heat to 100 ° C and react for 48 hours, then stop the reaction, remove the solvent, add ethyl acetate for extraction, combine the organic layers, wash with saturated brine, dry with anhydrous sodium sulfate, and concentrate by rotary concentration to obtain a crude product, which is separated and purified by 200-300 mesh silica gel column chromatography, with a petroleum ether / ethyl acetate volume ratio of 200:1 to 20:1, to obtain the target compound myrtenyl-1,3,4-oxadiazole carboxylic acid hydrazide derivative (Ⅰ-2). Pale yellow solid; yield: 34.5%.

[0066] Yellow solid; Yield: 35.0%; 1 H NMR(600MHz,Chloroform-d)δ9.26(s,1H),6.94–6.90(m,2H),6.86(ddt,J=9.0,6.7,3.1Hz,3H),3.06(td,J=5.6,1.5Hz, 1H),2.60–2.57(m,1H),2.52(tt,J=20.1,3.3Hz,2H),2.23–2.20(m,1H),1.38(s,3H),1.25(d,J=9.3Hz,1H),0.84(s,3H). 13C NMR(151MHz,Chloroform-d)δ166.18,158.42(d,J=238.5Hz),156.76,154.02,142.97(d,J=3.0Hz),134.7 4,132.11,115.98(d,J=24.0Hz),115.64(d,J=9.0Hz),42.19,40.30,38.10,32.66,31.33,25.87,21.02.MS ESI m / z:calcd forC 18 H 20 N4O2F[M+H]+:343.1570; found343.1573.

[0067] Example 3

[0068] Prepare myrtenyl-1,3,4-oxadiazolecarboxylic acid hydrazide derivative (I-3):

[0069]

[0070] Dissolve myrtenyl-1,3,4-oxadiazole methyl ester (500 mg, 2 mmol) in 15 ml pressure tube with 5 ml anhydrous DMF, add 4-chlorophenylhydrazine (710 mg, 5 mmol), heat to 100 ° C and react for 48 hours, then stop the reaction, remove the solvent, add ethyl acetate for extraction, combine the organic layers, wash with saturated brine, dry with anhydrous sodium sulfate, and concentrate by rotary concentration to obtain a crude product, which is separated and purified by 200-300 mesh silica gel column chromatography, and purified by petroleum ether / ethyl acetate volume ratio of 200:1 to 20:1 to obtain the target compound myrtenyl-1,3,4-oxadiazole carboxylic acid hydrazide derivative (Ⅰ-3). Pale yellow solid; yield: 34.5%

[0071] Light Yellow solid; Yield: 34.5%; 1 H NMR(600MHz,Chloroform-d)δ9.27(s,1H),7.18–7.15(m,2H),6.87(tt,J=3.2,1.4Hz,1H),6.83–6.79(m,2H),3.05(td,J= 5.6,1.5Hz,1H),2.60–2.57(m,1H),2.56–2.48(m,2H),2.23–2.20(m,1H),1.38(s,3H),1.25(d,J=9.3Hz,1H),0.84(s,3H). 13C NMR(151MHz,Chloroform-d)δ166.10,156.58,153.90,145.40,134.73,131.96 ,129.20,126.69,115.09,42.07,40.18,37.99,32.55,31.21,25.75,20.90.MS ESI m / z:calcd for C 18 H 19 N4O2NaCl[M+Na]+:381.1094; found 381.1089.

[0072] Example 4

[0073] Prepare myrtenyl-1,3,4-oxadiazolecarboxylic acid hydrazide derivative (I-4):

[0074]

[0075] Dissolve myrtenyl-1,3,4-oxadiazole methyl ester (500 mg, 2 mmol) in 15 ml pressure tube with 5 ml anhydrous DMF, add 4-bromophenylhydrazine (935 mg, 5 mmol), heat to 100 ° C and react for 48 hours, stop the reaction, remove the solvent, add ethyl acetate for extraction, combine the organic layers, wash with saturated brine, dry with anhydrous sodium sulfate, and concentrate to obtain a crude product. Separate and purify with 200-300 mesh silica gel column chromatography, and purify with petroleum ether / ethyl acetate volume ratio of 200:1 to 20:1 to obtain the target compound myrtenyl-1,3,4-oxadiazole carboxylic acid hydrazide derivative (Ⅰ-4). White solid; yield: 39.5%

[0076] White solid; Yield: 39.5%; 1 H NMR(600MHz,Chloroform-d)δ9.28(s,1H),7.33–7.29(m,2H),6.87(tt,J=3.4,1.5Hz,1H),6.78–6.74(m,2H),3.05(td,J=5.6, 1.5Hz,1H),2.58(dt,J=8.3,2.7Hz,1H),2.57–2.48(m,2H),2.23–2.20(m,1H),1.38(s,3H),1.25(d,J=9.3Hz,1H),0.84(s,3H). 13C NMR(151MHz,Chloroform-d)δ166.21,156.69,154.00,146.03,134.85,132.21 ,132.07,115.58,114.06,42.18,40.30,38.10,32.67,31.33,25.87,21.03.MS ESI m / z:calcd for C 18 H 19 N4O2NaBr[M+Na]+:425.0589; found 425.0585.

[0077] Example 5

[0078] Prepare myrtenyl-1,3,4-oxadiazolecarboxylic acid hydrazide derivative (I-5):

[0079]

[0080] Dissolve myrtenyl-1,3,4-oxadiazole methyl ester (500 mg, 2 mmol) in 15 ml pressure tube with 5 ml anhydrous DMF, add 4-iodophenylhydrazine (1170 mg, 5 mmol), heat to 100 ° C and react for 48 hours, stop the reaction, remove the solvent, add ethyl acetate for extraction, combine the organic layers, wash with saturated brine, dry with anhydrous sodium sulfate, and concentrate by rotary concentration to obtain a crude product, which is separated and purified by 200-300 mesh silica gel column chromatography, and purified by petroleum ether / ethyl acetate volume ratio of 200:1 to 20:1 to obtain the target compound myrtenyl-1,3,4-oxadiazole carboxylic acid hydrazide derivative (Ⅰ-5). Yellow oil; yield: 29.5%

[0081] Yellow oily substance; Yield: 29.5%; 1 H NMR(600MHz,Chloroform-d)δ9.00(s,1H),7.52(d,J=8.3Hz,2H),6.90–6.88(m,1H),6.67(d,J=8.5Hz,2H),3.07(td,J=5.6,1.5Hz,1 H),2.60(dt,J=8.5,2.8Hz,1H),2.58–2.49(m,2H),2.23(qd,J=5.7,4.7,2.4Hz,1H),1.39(s,3H),1.27(d,J=9.3Hz,1H),0.85(s,3H). 13C NMR(151MHz,)δ166.30,156.67,153.98,146.76,138.18,134.86,132.14,116.00,84.03,42.21,40.32,38.12,32.69,31.35,25.89,21.04.MS ESI m / z:calcd for C 18 H 19 N4O2NaI[M+Na]+:473.0450; found473.0441.

[0082] Example 6

[0083] Prepare myrtenyl-1,3,4-oxadiazolecarboxylic acid hydrazide derivative (I-6):

[0084]

[0086] Dissolve myrtenyl-1,3,4-oxadiazole methyl ester (500 mg, 2 mmol) in 15 ml pressure tube with 5 ml anhydrous DMF, add 4-methylphenylhydrazine (610 mg, 5 mmol), heat to 100 ° C and react for 48 hours, stop the reaction, remove the solvent, add ethyl acetate for extraction, combine the organic layers, wash with saturated brine, dry with anhydrous sodium sulfate, and concentrate to obtain a crude product. Separate and purify with 200-300 mesh silica gel column chromatography, and purify with petroleum ether / ethyl acetate volume ratio of 200:1 to 20:1 to obtain the target compound myrtenyl-1,3,4-oxadiazole carboxylic acid hydrazide derivative (Ⅰ-6). White solid; yield: 32.5%

[0087] White solid; Yield: 32.5%; 1 H NMR(600MHz,Chloroform-d)δ9.11(s,1H),7.04(s,1H),7.02(s,1H),6.87(tt,J=3.3,1.5Hz,1H),6.81(d,J=1.9Hz,1H),6.80(d,J=2.0Hz,1H) ,3.08(td,J=5.6,1.5Hz,1H),2.60–2.57(m,1H),2.57–2.48(m,2H),2.2 6(s,3H),2.22(m,1H),1.39(s,3H),1.26(d,J=9.3Hz,1H),0.85(s,3H). 13C NMR(151MHz,Chloroform-d)δ166.12,156.88,153.86,144.46,134.49,132.18,13 1.50,129.89,114.29,42.18,40.32,38.10,32.63,31.33,25.87,21.01,20.70.MS ESI m / z:calcd forC 19 H 22 N4O2Na[M+Na]+:361.1640; found361.1628.

[0088] Example 7

[0089] Prepare myrtenyl-1,3,4-oxadiazolecarboxylic acid hydrazide derivative (I-7):

[0090]

[0091] Dissolve myrtenyl-1,3,4-oxadiazole methyl ester (500 mg, 2 mmol) in 15 ml pressure tube with 5 ml anhydrous DMF, add 2-methylphenylhydrazine (610 mg, 5 mmol), heat to 100 ° C and react for 48 hours, stop the reaction, remove the solvent, add ethyl acetate for extraction, combine the organic layers, wash with saturated brine, dry with anhydrous sodium sulfate, and concentrate by rotary concentration to obtain a crude product, which is separated and purified by 200-300 mesh silica gel column chromatography, and purified by petroleum ether / ethyl acetate volume ratio of 200:1 to 20:1 to obtain the target compound myrtenyl-1,3,4-oxadiazole carboxylic acid hydrazide derivative (Ⅰ-7). White solid; yield: 42.5%

[0092] White solid; Yield: 42.5%; 1 H NMR(600MHz,Chloroform-d)δ9.04(s,1H),7.11(s,1H),7.10(s,1H),6.89(ddd,J=7.3,4.6,1.1Hz,3H),3.08(td,J=5.6,1.5Hz, 1H),2.60–2.57(m,1H),2.53(tt,J=20.0,3.1Hz,2H),2.29(s,3H),2.22(m,1H),1.39(s,3H),1.27(d,J=9.3Hz,1H),0.86(s,3H). 13C NMR(151MHz,Chloroform-d)δ166.18,156.85,153.69,144.61,134.58,132.18,130.83,12 7.14,123.74,121.87,112.67,42.20,40.33,38.11,32.66,31.35,25.89,21.04,17.17.MS ESI m / z:calcd for C 19 H 22 N4O2Na[M+Na]+:361.1640; found 361.1628.

[0093] Example 8

[0094] Prepare myrtenyl-1,3,4-oxadiazolecarboxylic acid hydrazide derivative (I-8):

[0095]

[0096] Dissolve myrtenyl-1,3,4-oxadiazole methyl ester (500 mg, 2 mmol) in 15 ml pressure tube with 5 ml anhydrous DMF, add 2-fluorophenylhydrazine (630 mg, 5 mmol), heat to 100 ° C and react for 48 hours, stop the reaction, remove the solvent, add ethyl acetate for extraction, combine the organic layers, wash with saturated brine, dry with anhydrous sodium sulfate, and concentrate by rotary concentration to obtain a crude product, which is separated and purified by 200-300 mesh silica gel column chromatography, and purified by petroleum ether / ethyl acetate volume ratio of 200:1 to 20:1 to obtain the target compound myrtenyl-1,3,4-oxadiazole carboxylic acid hydrazide derivative (Ⅰ-8). Yellow oil; yield: 22.5%

[0097] Yellow oily substance; Yield: 22.5%; 1 H NMR(600MHz,Chloroform-d)δ9.13(s,1H),7.04(ddd,J=11.3,8.0,1.3Hz,1H),7.00 (dd,J=7.6,1.4Hz,1H),6.97(td,J=8.2,1.9Hz,1H),6.89(tq,J=5.5,2.2Hz,2H),3. 07(td,J=5.6,1.6Hz,1H),2.59(dt,J=8.5,2.8Hz,1H),2.53(tt,J=20.1,3.3Hz,2H) ,2.22(dtd,J=6.1,3.2,1.5Hz,1H),1.39(s,3H),1.26(d,J=9.3Hz,1H),0.84(s,3H). 13C NMR(151MHz,Chloroform-d)δ166.23,156.71,153.91,151.68(d,J=240Hz),135.00(d,J=10.5Hz),134.70,132.16,124.68(d, J=4.5Hz),122.08(d,J=7.5Hz),115.52(d,J=18Hz),115.03(d,J=1.5Hz),42.18,40.31,38.10,32.66,31.33,25.87,21.02.MS ESI m / z:calcd for C 18 H 19 N4O2NaF[M+Na]+:365.1390; found365.1385.

[0098] Example 9

[0099] Prepare myrtenyl-1,3,4-oxadiazolecarboxylic acid hydrazide derivative (I-9):

[0100]

[0102] Dissolve myrtenyl-1,3,4-oxadiazole methyl ester (500 mg, 2 mmol) in 15 ml pressure tube with 5 ml anhydrous DMF, add 3-fluorophenylhydrazine (630 mg, 5 mmol), heat to 100 ° C and react for 48 hours, stop the reaction, remove the solvent, add ethyl acetate for extraction, combine the organic layers, wash with saturated brine, dry with anhydrous sodium sulfate, and concentrate to obtain a crude product, which is separated and purified by 200-300 mesh silica gel column chromatography, and purified by petroleum ether / ethyl acetate volume ratio of 200:1 to 20:1 to obtain the target compound myrtenyl-1,3,4-oxadiazole carboxylic acid hydrazide derivative (Ⅰ-9). White solid; yield: 32.5%

[0103] White solid; Yield: 32.5%; 1H NMR(600MHz,Chloroform-d)δ9.16(s,1H),7.17(td,J=8.2,6.4Hz,1H),6.88(tt,J=3.4,1.5Hz,1H),6.66(dd,J=7.6,2.1Hz,1H),6.61(td,J=9.1,2.3H z,2H),3.07(td,J=5.6,1.5Hz,1H),2.61–2.57(m,1H),2.57–2.48(m,2H),2 .22(dp,J=8.7,2.5Hz,1H),1.39(s,3H),1.26(d,J=9.3Hz,1H),0.85(s,3H). 13 C NMR(151MHz,Chloroform-d)δ166.23,163.81(d,J=214.5Hz),156.70,154.04,148.84(d,J=10.5Hz),134.81,132.10,130.67(d, J=9.0Hz),109.37(d,J=3.0Hz),108.45(d,J=21.0Hz),101.22(d,J=25.5Hz),42.17,40.30,38.09,32.65,31.32,25.85,21.00.MS ESIm / z:calcd for C 18 H 19 N4O2NaF[M+Na]+:365.1390; found 365.1386.

[0104] Example 10

[0105] Prepare myrtenyl-1,3,4-oxadiazolecarboxylic acid hydrazide derivative (I-10):

[0106]

[0107] Dissolve myrtenyl-1,3,4-oxadiazole methyl ester (500 mg, 2 mmol) in 15 ml pressure tube with 5 ml anhydrous DMF, add 2-chlorophenylhydrazine (710 mg, 5 mmol), heat to 100 ° C and react for 48 hours, stop the reaction, remove the solvent, add ethyl acetate for extraction, combine the organic layers, wash with saturated brine, dry with anhydrous sodium sulfate, and concentrate to obtain a crude product. Separate and purify with 200-300 mesh silica gel column chromatography, and purify with petroleum ether / ethyl acetate volume ratio of 200:1 to 20:1 to obtain the target compound myrtenyl-1,3,4-oxadiazole carboxylic acid hydrazide derivative (Ⅰ-10). White solid; yield: 29.5%

[0108] White solid; Yield: 32.5%;1 H NMR(600MHz,Chloroform-d)δ9.38(s,1H),7.28(dd,J=8.0,1.4Hz,1H),7.12(ddd,J=8.4,7.4,1.4Hz,1H),6.93(dd,J=8.2,1.5Hz,1H),6.88–6.83(m,2 H),6.68(s,1H),3.05(td,J=5.6,1.5Hz,1H),2.59–2.56(m,1H),2.56–2.47 (m,2H),2.22–2.19(m,1H),1.38(s,3H),1.24(d,J=9.3Hz,1H),0.83(s,3H). 13 C NMR(151MHz,Chloroform-d)δ166.16,156.72,153.81,142.87,134.71,132.09,129.66 ,127.83,122.04,119.79,113.86,42.13,40.28,38.06,32.63,31.30,25.84,20.99.MS ESIm / z:calcd for C 18 H 19 N4O2NaCl[M+Na]+:381.1094; found 381.1080.

[0109] Embodiment 11

[0110] Prepare myrtenyl-1,3,4-oxadiazolecarboxylic acid hydrazide derivative (I-11):

[0111]

[0112] Dissolve myrtenyl-1,3,4-oxadiazole methyl ester (500 mg, 2 mmol) in 15 ml pressure tube with 5 ml anhydrous DMF, add 3-chlorophenylhydrazine (710 mg, 5 mmol), heat to 100 ° C and react for 48 hours, stop the reaction, remove the solvent, add ethyl acetate for extraction, combine the organic layers, wash with saturated brine, dry with anhydrous sodium sulfate, and concentrate by rotary concentration to obtain a crude product, which is separated and purified by 200-300 mesh silica gel column chromatography, and purified by petroleum ether / ethyl acetate volume ratio of 200:1 to 20:1 to obtain the target compound myrtenyl-1,3,4-oxadiazole carboxylic acid hydrazide derivative (Ⅰ-11). Yellow oil; yield: 31.2%

[0113] Yellow oily substance; Yield: 31.2%; 1H NMR(600MHz,Chloroform-d)δ9.23(s,1H),7.13(t,J=8.3Hz,1H),6.89(ddd,J=5.0,2.8,1.5Hz,3H),6.76(ddd,J=8.2,2.2,1.0Hz,1H),3.06 (td,J=5.6,1.5Hz,1H),2.59(dt,J=7.9,2.6Hz,1H),2.56–2.48(m,2H),2.23–2.20(m,1H),1.38(s,3H),1.26(d,J=9.3Hz,1H),0.84(s,3H). 13 C NMR(151MHz,Chloroform-d)δ166.26,156.68,154.04,148.20,135.26,134.84,132.12 ,130.45,121.90,113.91,112.07,42.19,40.31,38.11,32.67,31.34,25.87,21.03.MS ESI m / z:calcd forC 18 H 19 N4O2NaCl[M+Na]+:381.1094; found 381.1080.

[0114] Example 12

[0115] Prepare myrtenyl-1,3,4-oxadiazolecarboxylic acid hydrazide derivative (I-12):

[0116]

[0118] Dissolve myrtenyl-1,3,4-oxadiazole methyl ester (500 mg, 2 mmol) in 15 ml pressure tube with 5 ml anhydrous DMF, add 2-bromophenylhydrazine (935 mg, 5 mmol), heat to 100 ° C and react for 48 hours, stop the reaction, remove the solvent, add ethyl acetate for extraction, combine the organic layers, wash with saturated brine, dry with anhydrous sodium sulfate, and concentrate by rotary concentration to obtain a crude product, which is separated and purified by 200-300 mesh silica gel column chromatography, and purified by petroleum ether / ethyl acetate volume ratio of 200:1 to 20:1 to obtain the target compound myrtenyl-1,3,4-oxadiazole carboxylic acid hydrazide derivative (Ⅰ-12). White oil; yield: 33.7%

[0119] White oily substance; Yield: 33.7%; 1H NMR (600MHz, Chloroform-d) δ8.98 (s, 1H), 7.48 (dd, J = 8.0, 1.4Hz, 1H), 7.20 (td, J = 7. 8,1.4Hz,1H),6.93(dd,J=8.1,1.5Hz,1H),6.90(tt,J=3.4,1.4Hz,1H),6.82(td,J=7. 6,1.5Hz,1H),6.57(s,1H),3.09(td,J=5.6,1.5Hz,1H),2.61–2.57(m,2H),2.52(dt,J =20.0,3.1Hz,1H),2.24–2.21(m,1H),1.39(s,3H),1.27(d,J=9.3Hz,1H),0.86(s,3H). 13 CNMR(151MHz,Chloroform-d)δ166.31,156.68,153.75,143.80,134.77,132.97,132.1 9,128.61,122.74,113.99,109.40,42.21,40.34,38.13,32.69,31.36,25.89,21.05.MS ESI m / z:calcd for C 18 H 19 N4O2NaBr[M+Na]+:425.0589; found425.0578.

[0120] Example 13

[0121] Prepare myrtenyl-1,3,4-oxadiazolecarboxylic acid hydrazide derivative (I-13):

[0122]

[0123] Dissolve myrtenyl-1,3,4-oxadiazole methyl ester (500 mg, 2 mmol) in 15 ml pressure tube with 5 ml anhydrous DMF, add 3-bromophenylhydrazine (935 mg, 5 mmol), heat to 100 ° C and react for 48 hours, stop the reaction, remove solvent, add ethyl acetate for extraction, combine the organic layers, wash with saturated brine, dry with anhydrous sodium sulfate, and concentrate by rotary concentration to obtain a crude product, which is separated and purified by 200-300 mesh silica gel column chromatography, and purified by petroleum ether / ethyl acetate volume ratio of 200:1 to 20:1 to obtain the target compound myrtenyl-1,3,4-oxadiazole carboxylic acid hydrazide derivative (Ⅰ-13). White oil; yield: 28.7%

[0124] White oily substance; Yield: 28.7%; 1H NMR(600MHz,Chloroform-d)δ9.00(s,1H),7.10(t,J=8.2Hz,1H),7.06(dt,J=7.2, 1.6Hz,2H),6.90(tt,J=3.3,1.4Hz,1H),6.83–6.80(m,1H),6.33(s,1H),3.08(td,J =5.6,1.5Hz,1H),2.60(dt,J=8.2,2.7Hz,1H),2.57(t,J=4.1Hz,1H),2.52(dt,J=20 .1,3.1Hz,1H),2.24–2.21(m,1H),1.39(s,3H),1.27(d,J=9.3Hz,1H),0.86(s,3H). 13 C NMR(151MHz,Chloroform-d)δ166.33,156.63,154.00,148.28,134.84,132.17,130.78 ,124.96,123.37,116.78,112.56,42.22,40.33,38.14,32.69,31.36,25.90,21.05.MS ESI m / z:calcd for C 18 H 20 N4O2Br[M+H]+:403.0770; found403.0764.

[0125] Embodiment 14

[0126] Prepare myrtenyl-1,3,4-oxadiazolecarboxylic acid hydrazide derivative (I-14):

[0127]

[0128] Dissolve myrtenyl-1,3,4-oxadiazole methyl ester (500 mg, 2 mmol) in 5 ml of anhydrous DMF in a 15 ml pressure tube, add 4-methoxyphenylhydrazine (690 mg, 5 mmol), heat to 100 ° C and react for 48 hours, stop the reaction, remove the solvent, add ethyl acetate for extraction, combine the organic layers, wash with saturated brine, dry with anhydrous sodium sulfate, and concentrate by rotary concentration to obtain a crude product, which is separated and purified by 200-300 mesh silica gel column chromatography, and purified by petroleum ether / ethyl acetate volume ratio of 200:1 to 20:1 to obtain the target compound myrtenyl-1,3,4-oxadiazole carboxylic acid hydrazide derivative (Ⅰ-14). White solid; yield: 22.7%

[0129] White solid; Yield: 28.7%; 1H NMR(600MHz,Chloroform-d)δ8.82(s,1H),6.90(d,J=2.2Hz,1H),6.90–6.88(m,2H),6.83(d,J=2.3Hz,1H),6.82(d,J=2.3Hz,1H),3.76(s,3 H),3.09(td,J=5.6,1.6Hz,1H),2.61–2.58(m,1H),2.55(dt,J=20.9,3.2Hz,2H),2.24–2.21(m,1H),1.39(s,3H),1.28(s,1H),0.85(s,3H). 13 C NMR(151MHz,Chloroform-d)δ166.21,156.85,155.47,153.88,140.34,134.54,13 2.22,116.31,114.83,55.76,42.23,40.35,38.13,32.67,31.36,25.90,21.04.MS ESI m / z:calcd for C 19 H 22 N4O2Na[M+Na]+:377.1590; found 377.1582.

[0130] Embodiment 15

[0131] Bactericidal activity (in vitro) experiment:

[0132] All the test strains in this experiment were purchased from the China Agricultural Microbial Culture Collection Center (ACCC) and the China Forestry Culture Collection Center (CFCC), including wheat fusarium rust (ACCC 31060), rice sheath blight (ACCC38870), pepper phytophthora (ACCC 36279), tomato gray mold (ACCC 36027), rapeseed sclerotinia (ACCC30096), pepper anthracnose (ACCC 37623) and potato infestation (ACCC 37629). MYA-1113 TM ). The culture medium used is potato agar glucose medium (PDA for short). PDA culture medium formula: 200g potato (peeled), 20g glucose, 15g agar, 1000mL distilled water, preparation method: wash and peel the potato, weigh 200g and cut into small pieces, add water and cook until soft (boil for 20-30 minutes, until it can be pierced by a glass rod), filter into a beaker with eight layers of gauze, add 15-20g agar according to experimental needs, add 20g glucose, stir evenly, cool slightly after fully dissolved, add water to 1000mL, sterilize at 121℃ for 15 minutes after packaging, and set aside after cooling.

[0133] Experimental method: Growth rate method was used.

[0134] (1) First, culture the seven plant fungi on a PDA plate at 25°C for about 3-6 days for later use;

[0135] (2) Heat and melt the PDA culture medium, cool it to 45-50°C, add 50 mg / L of the test compound to prepare a culture medium containing 50 mg / L of the drug solution, and pour it into culture dishes to cool. Bixafen is used as a positive control.

[0136] (3) Using aseptic operation procedures, use a cork puncher to punch a round bacterial cake (0.50 cm in diameter) at the edge of the hyphae of each strain after 6 days of culture (the growth conditions should be as consistent as possible), then use an inoculation needle to pick it to the center of the drug-containing plate, and then place the culture dish upside down in an incubator (28°C) for culture;

[0137] (4) Observe and measure the growth of mycelium at different times after treatment, measure the diameter using the cross method, process the data, and calculate the inhibition rate;

[0138] Inhibition rate (%) = (control mycelium diameter - treated mycelium diameter) / (control mycelium diameter - 0.5) × 100;

[0139] Each treatment was repeated 3 times.

[0140] Table 1 The results of the inhibitory activity test of myrtle 1,3,4-oxadiazole carboxylic acid hydrazide compounds against seven agricultural pathogenic fungi

[0141]

[0142]

[0143] Note: Each treatment was repeated three times in the experiment, and the data in the table are the average values ​​of the three repetitions.

[0144] Table 2 shows the EC values ​​of some compounds. 50 Value (mg / L)

[0145]

[0146]

[0147] The results of the bactericidal activity determination of the experimental groups I-1 to I-14 and the control agent carbendazim are shown in Table 1.

[0148] As shown in Table 1 and Table 2, at a concentration of 25 mg / L, compounds I-1 to I-14 showed different degrees of antifungal activity against 6 plant fungi, and some compounds showed relatively good antifungal activity against Sclerotinia sclerotiorum, Botrytis cinerea, Gibberella fusca, and Apple rot, and showed moderate inhibitory activity against Phytophthora infestans, Phytophthora capsici, and Botrytis cinerea. The inhibition rate of some compounds against Phytophthora infestans was higher than that of the control drug carbendazim. This indicates that the inhibitory activity of these compounds against the fungus is comparable to that of the positive control drug carbendazim, and has the potential to develop antifungal agents.

[0149] Depend on Figure 2 It can be seen that at different concentrations, the inhibition rate of compound I-4 on Botrytis cinerea and Gibberella fusca has a gradient change, which is consistent with the EC 50 The calculation results show that the compound has a good inhibitory effect on the above two pathogens.

[0150] Embodiment 17

[0151] Bactericidal in vivo experiment:

[0152] Apples with uniform texture and size and smooth texture were purchased from the market, washed with sterile water, then washed with 75% ethanol, and dried in the shade at room temperature. An appropriate amount of compound I-4 was weighed and prepared with a 0.2% Tween-80 aqueous solution to two concentrations of 200 mg / L and 100 mg / L.

[0153] Protective activity test method: Spray the surface of each apple (spray volume is 5mL, one concentration), spray evenly, and then dry naturally in the shade. After there is no liquid on the surface of the fruit, pierce the peel with an inoculation needle and inoculate the grape seat cavity pathogen cake (0.5cm diameter). Three cakes are inoculated on each fruit. The positive control is boscalid. Cultivate for 6 days under indoor conditions (25±2℃, and 95% relative humidity), measure the lesion diameter, and calculate the inhibition rate. The calculation formula of the inhibition rate (%): (blank control lesion diameter-test compound lesion diameter) / (blank control lesion diameter-0.5)x100%.

[0154] Protective activity test method: Spray the surface of each apple fruit (spray volume is 5mL, one concentration), spray evenly, and then dry naturally in the shade. After there is no liquid on the surface of the fruit, pierce the peel with an inoculation needle and inoculate the grape seat cavity pathogen cake (0.5cm diameter). Three cakes are inoculated on each fruit. The positive control is carbendazim. Culture for 6 days under indoor conditions (25±2℃, and 95% relative humidity), measure the lesion diameter, and calculate the inhibition rate. The calculation formula for the protective activity inhibition rate (%) is: (blank control lesion diameter-test compound lesion diameter) / (blank control lesion diameter-0.5)x100%.

[0155] Therapeutic activity test method: Pierce the fruit skin with an inoculation needle, inoculate the grape seat cavity pathogen cake (0.5cm diameter), three cakes per fruit, and then spray the surface of each apple fruit (spray volume is 5mL, one concentration, the positive control is carbendazim), spray evenly, and then dry naturally in the shade. After there is no liquid on the surface of the fruit, culture it under indoor conditions (25±2℃ and 95% relative humidity) for 6 days, measure the lesion diameter, and calculate the inhibition rate. The calculation formula of the protective activity inhibition rate (%): (blank control lesion diameter-test compound lesion diameter) / (blank control lesion diameter-0.5)x100%.

[0156] Table 3 Bioactivity of compound I-4 against Botrytis cinerea (live apple fruit)

[0157]

[0158] In Table 3 and Figure 3 It can be seen that at a concentration of 200 mg / L, the protective activity and therapeutic activity of compound I-4 were 92.1% and 85.0%, respectively, both better than the 74.3% and 63.5% of the positive control carbendazim. When the concentration was further reduced to 100 mg / L, the protective activity and therapeutic activity of compound I-4 were 77.9% and 75.2%, respectively, which were also better than the 33.4% and 39.9% of the positive control carbendazim. The results show that compound I-4 has potential value in the development of antifungal pesticides.

[0159] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention rather than to limit it. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of the present invention can be modified or replaced by equivalents without departing from the spirit and scope of the technical solutions of the present invention, which should all be included in the scope of the present invention.

Claims

1. Myrtle-1,3,4-oxadiazole carboxylic acid hydrazide compounds, characterized in that: The structural formula of the myrtle-1,3,4-oxadiazole carboxylic acid hydrazide compound is as follows: Among them, the R group is selected from one of 4-H, 4-F, 4-Cl, 4-Br, 4-I, 4-CH3, 2-CH3, 2-F, 3-F, 2-Cl, 3-Cl, 2-Br, 3-Br, and 3-O-CH3.

2. The method for preparing the myrtenyl-1,3,4-oxadiazolecarboxylic acid hydrazide compound according to claim 1, characterized in that: include, Myrtenal was oxidized to synthesize myrtenic acid; reacting myrtenic acid with hydrazine hydrate to form myrtenyl hydrazide; Myrtenyl hydrazide is reacted with methyl oxalyl chloride to produce myrtenyl-1,3,4-oxadiazole methyl ester; Myrtenyl-1,3,4-oxadiazole methyl ester is reacted with substituted phenylhydrazine to prepare myrtenyl-1,3,4-oxadiazole carboxylic acid hydrazide compounds.

3. The preparation method according to claim 2, characterized in that: The synthetic myrtle acid comprises: Dissolve myrtle aldehyde in acetonitrile, dissolve potassium dihydrogen phosphate in water, mix the two in a single-necked flask under ice bath conditions, add 30% hydrogen peroxide and PEG-400, dissolve sodium chlorite in water, slowly drop sodium chlorite aqueous solution using a 50 ml constant pressure funnel, react for 18 hours, and detect by TLC. After the reaction is complete, add sodium sulfite, rotate and concentrate to remove acetonitrile, add ethyl acetate for extraction, combine the organic layers, wash with saturated brine, dry with anhydrous sodium sulfate, and rotate and concentrate to obtain the target compound oily myrtle acid; Wherein, the molar ratio of myrtle aldehyde, potassium dihydrogen phosphate, hydrogen peroxide, PEG-400, sodium chlorite and sodium sulfite is 1:0.25:1.1:0.14:1.3:0.

07.

4. The preparation method according to claim 2, characterized in that: The synthetic myrtenyl hydrazide comprises: Dissolve myrtle acid in anhydrous dichloromethane, then add DMAP and EDCI, add 85% hydrazine hydrate dropwise in an ice bath, remove the ice bath after the addition, detect that the raw material reaction is complete by TLC, evaporate and concentrate to remove dichloromethane, add ethyl acetate for extraction, combine the organic layers, wash with saturated brine, dry with anhydrous sodium sulfate, and rotary concentrate to obtain a crude myrtle hydrazide, separate and purify with 200-300 mesh silica gel column chromatography, and purify with a petroleum ether / ethyl acetate volume ratio of 10:1 to 3:1 to obtain the target compound myrtle hydrazide; Wherein, the molar ratio of myrtle acid, DMAP, EDCI and hydrazine hydrate is 1:0.1:1.2:

2.

5. The preparation method according to claim 2, characterized in that: The synthetic myrtenyl-1,3,4-oxadiazole methyl ester comprises: Dissolve myrtenyl hydrazide in phosphorus oxychloride, add methyl oxalyl chloride dropwise in an ice bath, reflux at 85°C, react for 2 to 3 hours, pour the reaction solution into ice water and stir, add ethyl acetate for extraction, combine the organic layers, wash with saturated sodium bicarbonate, dry with anhydrous sodium sulfate, and concentrate by rotary centrifugation to obtain a crude product of myrtenyl-1,3,4-oxadiazole methyl ester, separate and purify by 200-300 mesh silica gel column chromatography, and purify by petroleum ether / ethyl acetate volume ratio of 200:1 to 50:1 to obtain the target compound myrtenyl-1,3,4-oxadiazole methyl ester; Wherein, the molar ratio of myrtle hydrazide to methyl oxalyl chloride is 1:1.

5.

6. The preparation method according to claim 2, characterized in that: The synthetic myrtenyl-1,3,4-oxadiazolecarboxylic acid hydrazide comprises: Dissolve myrtenyl-1,3,4-oxadiazole methyl ester in anhydrous DMF in a pressure tube, add substituted phenylhydrazine, heat to 100°C and react for 48 hours, then stop the reaction, remove the solvent, add ethyl acetate for extraction, combine the organic layers, wash with saturated brine, dry with anhydrous sodium sulfate, and rotary concentrate to obtain myrtenyl-1,3,4-oxadiazole carboxylic acid hydrazide of each substituent, separate and purify with 200-300 mesh silica gel column chromatography, and purify with petroleum ether / ethyl acetate volume ratio of 200:1 to 20:1 to obtain myrtenyl-1,3,4-oxadiazole carboxylic acid hydrazide of the target compound substituent; Wherein, the molar ratio of the myrtenyl-1,3,4-oxadiazole methyl ester to each substituted phenylhydrazine is 1:2.

5.

7. The preparation method according to any one of claims 2 to 6, characterized in that: The substituted phenylhydrazine includes phenylhydrazine, 4-fluorophenylhydrazine, 4-chlorophenylhydrazine, 4-bromophenylhydrazine, 4-iodophenylhydrazine, 4-methylphenylhydrazine, 2-methylphenylhydrazine, 2-fluorophenylhydrazine, 3-fluorophenylhydrazine, 2-chlorophenylhydrazine, 3-chlorophenylhydrazine, 2-bromophenylhydrazine, 3-bromophenylhydrazine, and 4-methoxyphenylhydrazine.

8. Use of the myrtenyl-1,3,4-oxadiazolecarboxylic acid hydrazide compound according to claim 1 in preventing and controlling plant fungi in agriculture or forestry.

9. The use according to claim 8, characterized in that: The plant fungi include Botrytis cinerea, Sclerotinia sclerotiorum, Botrytis cinerea, Phytophthora infestans and Phytophthora capsici.

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