Preparation method and application of a class of norbornene acyl thiourea compounds

Abstract

The application discloses a preparation method and application of a norbornene acyl thiourea compound, and relates to the following steps: synthesizing norbornene acyl chloride by acylating 5-norbornene-2-carboxylic acid, and then synthesizing norbornene acyl thiourea compound by reacting the norbornene acyl chloride with ammonium thiocyanate and substituted aniline; the compound has a general formula I: wherein R is selected from H, halogen and alkyl; the norbornene acyl thiourea is applied to preventing and treating fungal diseases on agricultural or forestry plants; and the activity results show that the norbornene acyl thiourea has good prevention effects on Sclerotinia sclerotiorum and Botryosphaeria dothidea; and the preparation method of the compound is simple, the yield is high, and the product is stable in property.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of pesticide synthesis, and particularly relates to a preparation method and application of a norbornene acyl thiourea compound. BACKGROUND

[0002] There are more than 19,000 fungi known worldwide that cause crop diseases, which destroy up to 30% of the agricultural and forestry crop products through plant diseases and spore transmission. The diversity of plant varieties brings the diversity of diseases and pests, which can cause fatal damage to the greening function and ornamental function of trees, and the use of fungicides is an important measure to maintain the health and high quality of agricultural products.

[0003] However, with the abuse of traditional fungicides and the long-term use of single-target fungicides, drug-resistant strains may become dominant, eventually leading to failure of disease control. Therefore, it is essential to develop new pesticide varieties with targeted effects for effective management of plant diseases.

[0004] Norbornene is an important bicyclic chemical entity, which is formed by the addition of cyclopentadiene and olefin. Its unique olefin double bond structure makes norbornene have special reactivity. The acyl thiourea group is not only an important organic synthesis structural unit, but also an important pharmacophore for developing new drugs and agricultural chemicals, but the synthesis method and anti-plant fungal activity of the acyl thiourea compound containing the norbornene group have not been reported so far.

[0005] At present, the preparation method of norbornene acyl thiourea compounds and its application in agricultural fungicides have not been reported. SUMMARY

[0006] This section aims to summarize some aspects of the embodiments of the present application and briefly introduce some preferred embodiments. Some simplifications or omissions may be made in this section and the abstract and title of the specification to avoid obscuring the purpose of this section, abstract and title, and such simplifications or omissions cannot be used to limit the scope of the present application.

[0007] In view of the above and / or problems existing in the prior art, the present application is proposed.

[0008] Therefore, the purpose of the present application is to overcome the deficiencies in the prior art, and to provide a preparation method of a norbornene acyl thiourea compound.

[0009] To solve the above technical problems, the present application provides the following technical scheme: a preparation method of a norbornene acyl thiourea compound, comprising,

[0010] 5-norbornene-2-carboxylic acid is acylated to synthesize norbornene acyl chloride;

[0011] The norbornene acyl chloride, ammonium thiocyanate and substituted aniline are reacted to synthesize the norbornene acyl thiourea compound;

[0012] The norbornene acyl thiourea compound has the structural formula:

[0013]

[0014] The norbornene acyl thiourea compound has the structural formula:

[0015]

[0016] As a preferred scheme of the preparation method, the synthesis of the norbornene acyl chloride comprises the following steps:

[0017] The oil 5-norbornene-2-carboxylic acid is dissolved in DCM, and DMF and oxalyl chloride are slowly added dropwise under ice bath condition, and after the addition, the reaction solution is transferred to 25℃ for stirring for 1.5-3h;

[0018] The solvent and excess oxalyl chloride are completely removed by a rotary vacuum evaporator to obtain the target compound, the norbornene acyl chloride.

[0019] As a preferred scheme of the preparation method, the molar ratio of the 5-norbornene-2-carboxylic acid, oxalyl chloride and DMF is 1:5:0.02.

[0020] The norbornene acyl chloride, ammonium thiocyanate and substituted aniline are reacted to synthesize the norbornene acyl thiourea compound;

[0021] The ammonium thiocyanate is dissolved in acetone, and the norbornene acyl chloride is slowly added dropwise under ice bath condition, and after the addition, the reaction solution is transferred to 25℃ for stirring for 1-1.5h, then the substituted aniline is added, and the stirring is continued at 60℃ for 1-2h, and the raw material is completely reacted by TLC detection, and the crude product is obtained by sequentially washing with water, saturated sodium bicarbonate and saturated sodium chloride and rotating concentration of the organic phase to remove most of the acetone;

[0022] Finally, the crude product is separated and purified by silica gel column chromatography with a mesh size of 200-300, and the volume ratio of petroleum ether to ethyl acetate is 20:1-5:1, to obtain the target compound, the norbornene acyl thiourea compound.

[0023] As a preferred scheme of the preparation method, the molar ratio of the norbornene acyl chloride, ammonium thiocyanate and substituted aniline is 1:1:1.

[0024] As a preferred scheme of the preparation method, the substituted aniline comprises 4-fluoroaniline, 4-chloroaniline, 4-bromoaniline, 4-iodoaniline, 4-trifluoromethoxyaniline, 4-isopropylaniline and 2,4-dichloroaniline.

[0025] Still another object of the present application is to provide a class of norbornenyl thiohydrazide compounds to overcome the deficiencies in the prior art.

[0026] Still another object of the present application is to provide the application of norbornenyl thiohydrazide compounds in preventing and treating plant fungi in agriculture or forestry, including Sclerotinia sclerotiorum and Botryosphaeria dothidea.

[0027] The present application has the following advantages:

[0028] (1) The norbornenyl thiohydrazide compounds of the present application have novel molecular structures, are new compounds, have distinct chemical structural characteristics, and contain norbornene and acyl thiohydrazide groups in the structural formula. The preparation method of the compounds is simple, the raw materials are easy to obtain, the reaction conditions are easy to control, and the product can be obtained by column chromatography.

[0029] (2) The compounds of the present application are a kind of fungicides for preventing and treating plant fungi in the field of agriculture or forestry, and have good prevention and treatment effect on Sclerotinia sclerotiorum and Botryosphaeria dothidea. BRIEF DESCRIPTION OF DRAWINGS

[0030] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings needed in the embodiment description will be briefly introduced below. Obviously, the drawings in the following description are only some embodiments of the present application, and other drawings can be obtained by those skilled in the art without creative labor. Among them:

[0031] Figure 1 The preparation method of norbornenyl thiohydrazide compounds in the embodiments of the present application is shown in the schematic diagram. DETAILED DESCRIPTION

[0032] In order to make the above-mentioned objects, features and advantages of the present application more apparent and easy to understand, the specific implementation manner of the present application will be described in detail below.

[0033] In the following description, many specific details are set forth in order to provide a thorough understanding of the present application, but the present application can also be implemented in other ways different from those described herein, and those skilled in the art can make similar generalizations without departing from the connotation of the present application, therefore the present application is not limited by the specific embodiments disclosed below.

[0034] Secondly, the "one embodiment" or "embodiment" referred to herein means that the specific features, structures or characteristics can be included in at least one implementation of the present application. "In one embodiment" appearing in different places in the specification does not mean the same embodiment, nor is it an independent or alternative embodiment that excludes other embodiments.

[0035] The preparation method of the norbornenoyl thiourea compound of the present application is shown in the following schematic diagram Figure 1 , which comprises the following steps:

[0036] (1) Synthesizing norbornenoyl chloride by acylation reaction of 5-norbornene-2-carboxylic acid;

[0037] (2) Synthesizing norbornenoyl thiourea by reaction of norbornenoyl chloride, substituted aniline and ammonium thiocyanate.

[0038] The specific steps are as follows:

[0039] (1) Preparation of norbornenoyl chloride

[0040] Dissolve the oily 5-norbornene-2-carboxylic acid (10 mmol) in DCM, and slowly drop DMF (0.2 mmol) and oxalyl chloride (50 mmol) in turn under ice bath condition. After the addition, transfer the reaction solution to 25℃ for stirring for 1.5-3h. Remove the solvent and excess oxalyl chloride completely by rotary vacuum evaporator to obtain the crude norbornenoyl chloride, and the target compound norbornenoyl chloride is obtained.

[0041] (2) Preparation of norbornenoyl thiourea

[0042] Dissolve ammonium thiocyanate (1 mmol) in acetone, and slowly drop norbornenoyl chloride (1 mmol) under ice bath. After the addition, transfer the reaction solution to 25℃ for stirring for about 1-1.5h, then add substituted aniline (1 mmol), and continue to stir at 60℃ for 1-2h. Detect the complete reaction of the raw material by TLC, and then wash with water, saturated sodium bicarbonate and saturated sodium chloride in turn. Concentrate the organic phase by rotary evaporation to remove most of the acetone to obtain the crude product. Finally, purify the crude product by column chromatography on a 200-300 mesh silica gel column, and elute with petroleum ether / ethyl acetate in a volume ratio of 20:1-5:1 to obtain the target compound norbornenoyl thiourea compound I-1-I-8.

[0043] 5-norbornene-2-carboxylic acid, oxalyl chloride, DMF, ammonium thiocyanate and substituted aniline are purchased from Shanghai Bide Technology Co., Ltd.; dichloromethane is purchased from Nanjing Wanqing Co., Ltd.; silica gel plate and silica gel powder are purchased from Yantai Haoyang Fine Chemical Co., Ltd.

[0044] Example 1

[0045] Dissolve ammonium thiocyanate (1 mmol) in acetone, drop the intermediate norbornene acyl chloride (1 mmol) under ice bath, react for 1-1.5 h at 25 ℃, then add 4- chloroaniline (1 mmol), react for 1-2 h at 60 ℃, TLC detects that the raw material is completely reacted, wash with water, saturated sodium bicarbonate, saturated sodium chloride in turn, concentrate and purify by column chromatography on 200-300 mesh silica gel, petroleum ether / ethyl acetate volume ratio 20:1-5:1, to get the target compound norbornene acyl thiourea compound I-2.

[0046]

[0047] I-1, white solid; yield 68.1%; mp: 128.2-128.5 ℃; 1 H NMR (600 MHz, chloroform) δ 12.26 (s, 1H), 8.88 (s, 1H), 7.59-7.55 (m, 2H), 7.09-7.04 (m, 2H), 6.33 (dd, J = 5.6, 3.1 Hz, 1H), 6.04 (dd, J = 5.7, 2.8 Hz, 1H), 3.27 (s, 1H), 3.03-2.99 (m, 2H), 2.02-1.97 (m, 1H), 1.53 (dq, J = 8.5, 2.1 Hz, 1H), 1.48-1.44 (m, 1H), 1.35 (d, J = 8.5 Hz, 1H). 13 C NMR (150 MHz, chloroform) δ 178.72, 175.52, 160.87 (d, J = 246.0 Hz), 138.78, 133.49 (d, J = 3 Hz), 131.37, 126.10 (d, J = 9 Hz), 115.68 (d, J = 22.5 Hz), 50.25, 46.62, 46.01, 42.85, 29.55.

[0048] Example 2

[0049] Dissolve ammonium thiocyanate (1 mmol) in acetone, drop the intermediate norbornene acyl chloride (1 mmol) under ice bath, react for 1-1.5 h at 25 ℃, then add 4- chloroaniline (1 mmol), react for 1-2 h at 60 ℃, TLC detects that the raw material is completely reacted, wash with water, saturated sodium bicarbonate, saturated sodium chloride in turn, concentrate and purify by column chromatography on 200-300 mesh silica gel, petroleum ether / ethyl acetate volume ratio 20:1-5:1, to get the target compound norbornene acyl thiourea compound I-2.

[0050]

[0051] I-2, white solid; yield 71.8%; mp: 147.2-147.5 ℃;1 H NMR (600 MHz, Chloroform) δ 12.35 (s, 1H), 8.82 (s, 1H), 7.60 (d, J = 8.8 Hz, 2H), 7.36 - 7.32 (m, 2H), 6.33 (dd, J = 5.6, 3.1 Hz, 1H), 6.04 (dd, J = 5.6, 2.7 Hz, 1H), 3.27 (s, 1H), 3.02 - 2.99 (m, 2H), 2.02 - 1.98 (m, 1H), 1.55 - 1.52 (m, 1H), 1.48 - 1.43 (m, 1H), 1.35 (d, J = 8.4 Hz, 1H). 13 C NMR (150 MHz, Chloroform) δ 178.54, 175.78, 138.97, 136.26, 132.22, 131.56, 129.11, 125.42, 50.45, 46.86, 46.21, 43.06, 29.77.

[0052] Example 3

[0053] Dissolve ammonium thiocyanate (1 mmol) in acetone, drop intermediate norbornene acid chloride (1 mmol) under ice bath, react at 25°C for 1-1.5 h, then add 4-bromoaniline (1 mmol), react at 60°C for 1-2 h, TLC detects that the raw material is completely reacted, wash with water, saturated sodium bicarbonate, saturated sodium chloride in turn, concentrate and separate and purify by 200-300 mesh silica gel column chromatography, the volume ratio of petroleum ether / ethyl acetate is 20:1-5:1, to get the target compound norbornene acyl thiourea compound I-3.

[0054]

[0055] I-3, white solid; yield 62.5%; mp: 169.2-170.1°C; 1 H NMR (600 MHz, Chloroform) δ 12.35 (s, 1H), 8.82 (s, 1H), 7.60 (d, J = 8.8 Hz, 2H), 7.36 - 7.32 (m, 2H), 6.33 (dd, J = 5.6, 3.1 Hz, 1H), 6.04 (dd, J = 5.6, 2.7 Hz, 1H), 3.27 (s, 1H), 3.02 - 2.99 (m, 2H), 2.02 - 1.98 (m, 1H), 1.55 - 1.52 (m, 1H), 1.48 - 1.43 (m, 1H), 1.35 (d, J = 8.4 Hz, 1H). 13CNMR (150 MHz, chloroform) δ 178.22, 175.56, 138.76, 136.57, 131.87, 131.34, 125.46, 119.84, 50.24, 46.65, 46.01, 42.85, 29.57.

[0056] Example 4

[0057] Dissolve ammonium thiocyanate (1 mmol) in acetone, drop in intermediate norbornene acid chloride (1 mmol) under ice bath, react for 1-1.5 h at 25 °C, then add 4-iodoaniline (1 mmol), react for 1-2 h at 60 °C, TLC detection of complete reaction of raw materials, wash with water, saturated sodium bicarbonate, saturated sodium chloride in turn, concentrate and purify by 200-300 mesh silica gel column chromatography, petroleum ether / ethyl acetate volume ratio 20:1-5:1, to get the target compound norbornene acyl thiourea compound I-4.

[0058]

[0059] I-4, white solid; yield 68.7%; mp: 179.2-180.5 °C; 1 H NMR (600 MHz, chloroform) δ 12.35 (s, 1H), 8.82 (s, 1H), 7.70-7.67 (m, 2H), 7.45-7.42 (m, 2H), 6.33 (dd, J = 5.6, 3.1 Hz, 1H), 6.03 (dd, J = 5.6, 2.8 Hz, 1H), 3.26 (s, 1H), 3.03-2.99 (m, 2H), 2.02-1.98 (m, 1H), 1.55-1.52 (m, 1H), 1.47-1.44 (m, 1H), 1.36-1.33 (m, 1H). 13 C NMR (150 MHz, chloroform) δ 177.90, 175.35, 138.54, 137.61, 137.07, 131.13, 125.39, 90.76, 50.03, 46.44, 45.79, 42.64, 29.35.

[0060] Example 5

[0061] Dissolve ammonium thiocyanate (1 mmol) in acetone, drop the intermediate norbornene acid chloride (1 mmol) under ice bath, react for 1-1.5 h at 25 °C, then add the substituted 4-trifluoromethoxy aniline (1 mmol), react for 1-2 h at 60 °C, TLC detects that the raw material is completely reacted, wash with water, saturated sodium bicarbonate, saturated sodium chloride in turn, concentrate and purify by column chromatography on 200-300 mesh silica gel, the volume ratio of petroleum ether / ethyl acetate is 20:1-5:1, to get the target compound norbornene acyl thiourea compound I-5.

[0062]

[0063] I-5, white solid; yield 68.5%; mp: 169.2-169.5 °C; 1H NMR (600 MHz, chloroform) δ 12.39 (s, 1H), 8.73 (s, 1H), 7.71-7.68 (m, 2H), 7.23 (d, J = 8.6 Hz, 2H), 6.34 (dd, J = 5.6, 3.1 Hz, 1H), 6.04 (dd, J = 5.6, 2.8 Hz, 1H), 3.28 (s, 1H), 3.01 (m, 2H), 2.03-1.99 (m, 1H), 1.56-1.53 (m, 1H), 1.48-1.45 (m, 1H), 1.36 (d, J = 8.5 Hz, 1H). 13 C NMR (151 MHz, chloroform) δ 178.44, 175.61, 147.10 (q, J = 1.65 Hz) 138.87, 136.03, 131.37, 125.30, 121.32, 120.40 (q, J = 255.9 Hz), 50.29, 46.67, 46.09, 42.89, 29.61.

[0064] Example 6

[0065] Dissolve ammonium thiocyanate (1 mmol) in acetone, drop the intermediate norbornene acid chloride (1 mmol) under ice bath, react for 1-1.5 h at 25 °C, then add the substituted 4-trifluoromethoxy aniline (1 mmol), react for 1-2 h at 60 °C, TLC detects that the raw material is completely reacted, wash with water, saturated sodium bicarbonate, saturated sodium chloride in turn, concentrate and purify by column chromatography on 200-300 mesh silica gel, the volume ratio of petroleum ether / ethyl acetate is 20:1-5:1, to get the target compound norbornene acyl thiourea compound I-5.

[0066]

[0067] I-6, white solid; yield 69.8%; mp: 115.2-115.9 °C; 1H NMR (600 MHz, Chloroform) δ 12.28 (s, 1H), 8.92 (s, 1H), 7.55 (d, J = 8.4 Hz, 2H), 7.24 (d, J = 8.4 Hz, 2H), 6.33 (dd, J = 5.6, 3.1 Hz, 1H), 6.04 (dd, J = 5.6, 2.8 Hz, 1H), 3.27 (s, 1H), 3.04 - 2.98 (m, 2H), 2.93 - 2.89 (m, 1H), 2.00 - 1.97 (m, 1H), 1.54 - 1.51 (m, 1H), 1.48 - 1.45 (m, 1H), 1.35 (d, J = 8.4 Hz, 1H), 1.25 (s, 3H), 1.24 (s, 3H). 13 C NMR (150 MHz, Chloroform) δ 177.85, 175.22, 147.24, 138.40, 134.93, 131.17, 126.51, 123.67, 49.99, 46.43, 45.68, 42.61, 33.47, 29.27, 23.62.

[0068] Example 7

[0069] Ammonium thiocyanate (1 mmol) was dissolved in acetone, and intermediate norbornene acid chloride (1 mmol) was added dropwise under ice bath, and reacted at 25°C for 1-1.5 h, then 2,4-dichloroaniline (1 mmol) was added, and reacted at 60°C for 1-2 h. TLC was used to detect the completion of the reaction. After washing with water, saturated sodium bicarbonate, and saturated sodium chloride, the target compound norbornene acyl thiourea compound I-7 was obtained by column chromatography on 200-300 mesh silica gel with petroleum ether / ethyl acetate (volume ratio 20:1-5:1).

[0070]

[0071] I-7, white solid; yield 65.5%; mp: 179.5-180.5°C; 1 H NMR (600 MHz, Chloroform) δ 12.45 (s, 1H), 8.65 (s, 1H), 8.33 (d, J = 8.8 Hz, 1H), 7.45 (d, J = 2.3 Hz, 1H), 7.28 (dd, J = 8.8, 2.3 Hz, 1H), 6.35 (dd, J = 5.6, 3.1 Hz, 1H), 6.05 (dd, J = 5.6, 2.8 Hz, 1H), 3.29 (s, 1H), 3.04 - 3.01 (m, 2H), 2.04 - 2.00 (m, 1H), 1.57 - 1.54 (m, 1H), 1.50 - 1.47 (m, 1H), 1.37 (d, J = 8.5 Hz, 1H). 13CNMR (150 MHz, chloroform) δ 178.74, 175.41, 138.96, 132.35, 131.32, 129.38, 128.63, 127.14, 126.99, 50.29, 46.68, 46.04, 42.89, 29.48.

[0072] Example 8

[0073] Bactericidal activity (in vitro) experiment

[0074] All test strains in this experiment were purchased from the official website of China Agricultural Microbial Culture Collection Center (ACCC) and China Forestry Microbial Culture Collection Center (CFCC), and were Sclerotinia sclerotiorum, Gibberella zeae, Botryosphaeria dothidea, Phytophthora capsici, Phytophthora infestans, Phytophthora nicotianae and Botrytis cinerea. The culture medium used was potato agar glucose medium (PDA for short). The PDA medium formula: potato (peeled) 200 g, glucose 20 g, agar 15 g, distilled water 1000 mL, preparation method: wash and peel the potato, weigh 200 g and cut into small pieces, cook until soft (boil for 20-30 minutes, which can be poked by a glass rod), filter in a beaker with eight layers of gauze, add 20 g of agar according to the experimental needs, add 20 g of glucose, stir evenly, dissolve thoroughly, cool slightly, make up to 1000 mL with water, sterilize at 121°C for 15 minutes after dispensing, and cool down for standby.

[0075] Experimental method: growth rate method.

[0076] (1) First, 7 kinds of plant fungi were cultured on PDA plates at 25°C for 3-6 days for standby;

[0077] (2) Heat the PDA culture medium to dissolve it, cool it to 45-50°C, add 125 μL of 10 g / L concentration of the test compound to make a culture medium containing 50 mg / L of the test compound, and pour it into the culture dish and cool it down. Boscalid was used as a positive control;

[0078] (3) Using aseptic operation, use a punch to take a round fungus cake (diameter 0.50 cm) at the edge of the mycelium of each strain cultured for 6 days (the growth conditions are as consistent as possible), then use a inoculation needle to pick it up in the center of the drug-containing plate, and then invert the culture dish in the incubator (28°C) for culture;

[0079] (4) Observe and measure the growth of mycelium at different times after treatment, and measure the diameter by cross method and process the data to calculate the inhibition rate;

[0080] (5) Inhibition rate (%) = (control mycelium diameter - treated mycelium diameter) / (control mycelium diameter - 0.5) x 100;

[0081] (6) Each treatment was repeated 3 times.

[0082] Table 1 is the test result of the inhibitory activity of norbornenylthiourea compounds against seven agricultural pathogenic fungi (25 mg / L).

[0083]

[0084] Note: Each treatment was repeated three times in the test, and the data in the table is the average of three repetitions.

[0085] Table 2 is the EC 50 value (mg / L) of some compounds.

[0086]

[0087] The results of the bactericidal activity determination of experimental groups I-1 to I-7 and the control agent, boscalid, are shown in Tables 1 and 2. As shown in Table 1, at a concentration of 25 mg / L, compounds I-1 to I-7 showed different degrees of bacteriostatic activity against seven plant fungi, some of which showed excellent bacteriostatic activity against Sclerotinia sclerotiorum and Botryosphaeria dothidea, and moderate to good inhibitory activity against Gibberella zeae and Phytophthora nicotianae. Among them, compound I-1 had an inhibition rate of 88.9% against Sclerotinia sclerotiorum and 88.0% against Botryosphaeria dothidea, which was slightly higher than the positive control drug boscalid 87.7%.

[0088] In view of the good inhibitory activity of some target compounds against Sclerotinia sclerotiorum and Botryosphaeria dothidea, the EC 50 values of some compounds with higher inhibition rates were tested. As shown in Table 2, I-1 and I-4 had lower EC 50 values against Sclerotinia sclerotiorum and Botryosphaeria dothidea, especially compound I-1 had an EC 50 value of 2.82 mg / L against Sclerotinia sclerotiorum. As shown by the results in Tables 1 and 2, the compounds in this series have good inhibitory activity against Sclerotinia sclerotiorum and Botryosphaeria dothidea, and have the potential to develop bactericides.

[0089] Example 9

[0090] The reaction conditions and yields of the synthesis of norbornenyl chloride from 5-norbornene-2-carboxylic acid by acylation reaction under different reaction conditions were investigated, and the conditions and results are shown in Table 3.

[0091] Table 3

[0092]

[0093] The reaction and yield of three acylation conditions are discussed, wherein the acylation condition of DMF / oxalyl chloride has the highest yield (91.6%); the acylation condition of oxalyl chloride has a slightly lower yield (85.5%); and the acylation condition of dichlorosulfide has the lowest yield (35%). Therefore, the acylation reaction using DMF / oxalyl chloride as the reaction condition is the best.

[0094] Example 10

[0095] Under the conditions of Example 1, the reaction and yield of norbornene acyl chloride to synthesize norbornene acyl thiourea under different reaction conditions are investigated, and the conditions and results are shown in Table 4.

[0096] Table 4

[0097]

[0098] The effects of two conditions on the reaction and yield of norbornene acyl thiourea are discussed, wherein the reaction condition of ammonium thiocyanate has the highest yield (68.1%); and the reaction condition of potassium thiocyanate has the lowest yield (29.5%). Therefore, the ammonium thiocyanate is the best reaction condition for synthesizing the norbornene acyl thiourea.

[0099] The norbornene acyl thiourea compound has obvious structural differences and distinct chemical structural characteristics, and shows good effects on preventing and treating sclerotinia sclerotiorum and botryosphaeria dothidea. The compound can be used for preventing and treating fungal diseases of agricultural or forestry plants. The preparation method of the compound is simple, the yield is high, and the product is stable in property.

[0100] It should be noted that the above examples are only used to illustrate the technical solutions of the present application and are not limited. Although the present application has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that the technical solutions of the present application can be modified or replaced by equivalents without departing from the spirit and scope of the present application, and they should be included in the scope of the present application.

Claims

1. A process for the preparation of a class of norbornenoyl thiourea compounds, characterized by: The preparation method comprises the following steps: The 5-norbornene-2-carboxylic acid is dissolved in DCM, and DMF and oxalyl chloride are slowly added dropwise under ice bath condition, and the reaction solution is transferred to 25 DEG C for stirring for 1.5-3 h; the solvent and excess oxalyl chloride are completely removed by a rotary vacuum evaporator, and the target compound norbornenyl chloride is obtained in an oily form; The norbornenyl chloride, ammonium thiocyanate and substituted aniline are reacted to synthesize norbornenyl thiourea compounds. The norbornenyl thiourea compounds have the following structural formula: ； The R is selected from 4-F, 4-Cl, 4-Br, 4-I, 4-OCF3, 4-CH(CH3)2 and 2,4-diCl groups.

2. The production method according to claim 1, characterized by: The molar ratio of the 5-norbornene-2-carboxylic acid, oxalyl chloride and DMF is 1:5:0.

02.

3. The production method according to claim 1, wherein: The synthesis of the norbornenyl thiourea compounds comprises the following steps: The ammonium thiocyanate is dissolved in acetone, and the norbornenyl chloride is slowly added dropwise under ice bath condition; after the addition, the reaction solution is transferred to 25 DEG C for stirring for 1-1.5 h, then the substituted aniline is added, and the stirring is continued at 60 DEG C for 1-2 h; the raw material is completely reacted by TLC detection, and the crude product is obtained by sequentially washing with water, saturated sodium bicarbonate and saturated sodium chloride and rotatingly concentrating the organic phase to remove most of the acetone; Finally, the crude product is separated and purified by column chromatography with 200-300 mesh silica gel, and the target compound norbornenyl thiourea compound is obtained by using petroleum ether / ethyl acetate with a volume ratio of 20:1-5:

1.

4. The production method according to claim 3, characterized by: The molar ratio of the norbornenyl chloride, ammonium thiocyanate and substituted aniline is 1:1:

1.

5. The production method according to any one of claims 1 to 4, characterized by: The substituted aniline comprises 4-fluoroaniline, 4-chloroaniline, 4-bromoaniline, 4-iodoaniline, 4-trifluoromethoxyaniline, 4-isopropylaniline and 2,4-dichloroaniline.

6. The norbornenyl thiourea compound prepared by the preparation method in any one of claims 1-5.

7. The use of the norbornene acylthiourea compound according to claim 6 for the control of plant fungi in agriculture or forestry, characterized in that: The plant fungi are Sclerotinia sclerotiorum and Botryosphaeria dothidea.

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