Zinc pentathiocenium and its manufacturing method and uses

Abstract

The present invention provides a novel active ingredient that exhibits a stable control effect against bacterial plant diseases, particularly against diseases that are difficult to control, such as rice bacterial leaf blight and tomato bacterial wilt, and that is low in toxicity and places little burden on the environment. The present invention provides a pentathiocenium zinc metal complex, its preparation method, and its use. The pentathiocenium zinc metal complex includes pentathiocenium zinc, or a stereoisomer thereof, or a salt thereof, or a solvate thereof, and has the chemical structure represented by the following formula: JPEG0007798278000032.jpg65125

Description

[Technical Field]

[0001] The present invention is in the field of chemistry and agrochemistry, in particular Zinc pentathiocenium ( Pentathiocenium zinc ) and its manufacturing method and use. [Background technology]

[0002] Bacterial plant diseases are a type of plant disease caused by bacteria and are the third major type of plant disease after fungal and viral diseases. For example, bacterial diseases such as rice bacterial leaf blight, rice bacterial streak, citrus canker, tobacco bacterial wilt, and tomato bacterial wilt are considered to be globally significant. In recent years, due to changes in Japan's crop cultivation system and climatic environment, bacterial crop diseases such as rice bacterial leaf blight, rice bacterial streak, citrus canker, citrus yellow dragon disease, tomato bacterial wilt, tobacco bacterial wilt, peach hole, cabbage black rot, Chinese cabbage soft rot, melon bacterial angular spot, and watermelon bacterial fruit rot have shown a serious tendency to occur in Japan. These diseases are characterized by rapid onset, extensive damage, and widespread distribution. The long-term use of conventional fungicides has led to a certain degree of resistance in plant pathogens, making the control effect insufficient. As a result, there are currently no effective chemical agents or other superior control methods, resulting in significant losses in agricultural production.

[0003] The 1,3,4-pentathiocenium fungicide, pentathiocenium-copper fungicide for leaf blight (also known as thiaxol or yeqingshuang), has the molecular formula C5H6N6S4 and is a systemic fungicide used to control plant bacterial diseases. It was independently created and developed by the Sichuan Chemical Industry Research Institute, China. Pentathiocenium-copper fungicide for leaf blight appears as white rectangular prism crystals or pale yellow powder. The mechanism of action of thiaxol is that the pentathiocenium skeleton inhibits the amino acid metabolism of pathogenic fungi, thereby preventing protein biosynthesis and suppressing mycelial growth. While thiaxol is not carcinogenic, teratogenic, or mutagenic, it is susceptible to photolysis and hydrolysis, producing dixol through desulfurization. Dixol is included in the list of pesticides specifically banned in China due to its strong teratogenic and thyrotoxic properties.

[0004] To overcome these drawbacks, Zhejiang Longwan Chemical Co., Ltd. developed the highly efficient, low-toxicity systemic fungicide "Tiadinil Copper (trade name: Longke)" in 1998. Its active ingredient is "2-amino-5-thio-1,3,4-pentathiocenium copper complex," as detailed in Chinese Patent Publication No. CN1227224A. This fungicide is used to control bacterial and fungal diseases such as rice bacterial leaf blight and rice bacterial streak, and is also effective on a variety of crops, including fruit trees and vegetables. However, long-term and intensive use has led to increased resistance in pathogens, leading to significant problems such as spider mites and copper poisoning. Therefore, the development of a new, highly efficient, low-toxic, and low-residue green fungicide has become an urgent issue in agricultural production.

[0005] 1,3,4-Pentathiocenium derivatives possess a wide range of agricultural and medical biological activities, with 1,3,4-pentathiocenium being a representative structure within this group. Their biological activities include fungicides, antivirals, herbicides, insecticides, antioxidants, anti-inflammatory agents, anticancer agents, antimalarials, antitumors, antituberculosis agents, and anti-AIDS agents. Therefore, research into their molecular design, synthesis, and biological activity is an important research topic in the development of green pesticides. A literature review reveals that 1,3,4-pentathiocenium derivatives are currently being widely studied and applied as fungicides and herbicides.

[0006] In 2014, Song Bao'an et al. (Song Bao'an, Li Pei, Yang Song, Hu Deyu, Xue Wei, Jin Linhong, Xu Weiming, Heming, Shi Li, Yang Xia, Shi Qingcai, Wu Fang. Thiadiazolemetal complexes and their application in controlling agricultural plant diseases [P]. CN103788119A, 2014) reported a series of pentathiocenium-based metal complexes that were effective against fungal pathogens such as Fusarium head blight, Pepper wilt, and Apple rot, as well as bacterial pathogens such as rice bacterial leaf blight and tobacco bacterial wilt, demonstrating their potential application in controlling fungal and bacterial diseases in crops.

[0007] In 2018, Cui Zining et al. (Cui Zining, Tao Hui, Tian Hao, Xiang Xuwen, Jiang Shan, Zhang Lianhui. Application of 1,3,4-thiadiazole compounds in the control of bacterial leaf blight of rice [P]. CN107535504B, 2018) reported that S-(5-substituted-1,3,4-pentathiocenium)-(5-substituted phenyl)-2-furanthiocarboxylic acid ester derivatives have excellent biological activity in the control of rice bacterial leaf blight and can be used as T3SS activity inhibitors.

[0008] In 2019, Song Bao'an et al. (Song Bao'an, Chen Jixiang, Yang Song, Zeng Song, He Wu, Tian Pingyi, Zhou Dagui, Yi Chongfen, Limingwei, Wang Yanjiao, Li Xiangyang. Disulfide derivatives containing 1,3,4-oxadiazole (thiadiazole), their preparation methods and applications [P]. CN106632129B, 2019) reported on disulfide derivatives containing 1,3,4-oxa(thia)diazole, which showed nematicidal activity and application in suppressing bacterial crop diseases.

[0009] In addition, in 2019, Song Baoan et al. (Wu, Q., Cai, H., Yuan, T., Li, SY, Gan, XH, Song, BA Novel vanillin derivatives containing a 1,3,4-thiadiazole moiety as potential antibacterial agents [J]. Bioorg.med. Chem. Lett. 2020, 30, 127113.) designed and synthesized vanillin derivatives containing a 1,3,4-pentathiocenium structure and demonstrated that many of them had excellent inhibitory activity against the rice bacterial streak pathogen. Other patents related to fungicides include CN1292217A, CN1308070A, and CN105541822A, and patents related to herbicides include CN101157665A, CN109053634A, CN106212482A, and CN107721948A. Therefore, research into structurally novel 1,3,4-pentathiocenium fungicides is of great significance.

[0010] The present invention aims to provide a novel, highly effective, and low-toxic pesticide variety for controlling bacterial diseases of crops, such as rice bacterial leaf blight, rice bacterial streak, citrus canker, citrus yellow dragon disease, tomato bacterial wilt, tobacco bacterial wilt, peach hole disease, cabbage black rot, Chinese cabbage soft rot, melon bacterial angular spot, and watermelon bacterial fruit rot. [Prior art documents] [Patent documents]

[0011] [Patent Document 1] China Patent Publication CN103788119A [Patent Document 2] China Patent Publication CN107535504B [Patent Document 3] China Patent Publication CN106632129B [Patent Document 4] China Patent Publication Publication CN1292217A [Patent Document 5] China Patent Publication CN1308070A [Patent Document 6] China Patent Publication CN105541822A [Patent Document 7] China Patent Publication CN105541822A [Patent Document 8] China Patent Publication CN101157665A [Patent Document 9] China Patent Publication CN109053634A [Patent Document 10] China Patent Publication CN106212482A [Patent Document 11] China Patent Publication CN107721948A [Non-patent literature]

[0012] [Non-Patent Document 1] Wu, Q., Cai, H., Yuan, T., Li, SY, Gan, XH, Song, BA Novel vanillin derivatives containing a 1,3,4-thiadiazolemoiety as potential antibacterial agents [J]. Bioorg.med. Chem. Lett. 2020, 30, 127113. Summary of the Invention [Problem to be solved by the invention]

[0013] One of the objects of the present invention is to Zinc pentathiocenium and a method for producing the same.

[0014] Another object of the present invention is to provide the above Zinc pentathiocenium The present invention provides a composition comprising:

[0015] A further object of the present invention is to provide the above Zinc pentathioceniumOr to provide uses of the composition.

[0016] Another object of the present invention is to provide the above Zinc pentathiocenium Another object of the present invention is to provide a method for controlling bacterial plant diseases using the composition. [Means for solving the problem]

[0017] Specifically, this is achieved by the following technical means: P thiocenium zinc, or its stereoisomer, or its salt, or its solvate And The zinc pentathiocenium is a "chloro-bis[5,11,17-trithia-1,3,7,9,13,15,19,20,21-nonazatria ring [14.2.1.1 4,7 .1 10,13 ]heneicosa-4(20),10(21),16(19)-triene-6,12,18-trithione]zinc complex, and its chemical structure is shown in Formula I.

[0018] JPEG0007798278000002.jpg74154

[0019] The method for producing the above-mentioned zinc pentathiocenium includes the following steps. 2-Amino-5-thio-1,3,4-pentathiocenium is used as the starting material. Water is added as the solvent, and NaOH is added as an acid scavenger. After dissolving by stirring, formaldehyde or paraformaldehyde solution is gradually added and the reaction is allowed to proceed at room temperature (25±5°C) for 1-2 hours. Dilute hydrochloric acid is then added to recrystallize the precipitated solid, which is then vacuum filtered and suction dried at 50-70°C to give 5,11,17-trithia-1,3,7,9,13,15,19,20,21-nonazatria ring [14.2.1.1 4,7 .1 10,13 ] Henicosa-4(20),10(21),16(19)-triene-6,12,18-trithione (hereinafter referred to as "intermediate X5") is obtained.

[0020] Next, intermediate X5 is used as a raw material, and water is added as a solvent. NaOH is added as an acid scavenger. Finally, zinc chloride dissolved in water is added to the reaction system and reacted at room temperature for 1 to 2 hours. After the reaction is complete, water is added and the precipitated solid is filtered using a Buchner funnel. After filtration, the solid is dried and the metal complex "chloro-bis[5,11,17-trithia-1,3,7,9,13,15,19,20,21-nonazatria[14.2.1.1 4,7 .1 10,13 ]heneicosa-4(20),10(21),16(19)-triene-6,12,18-trithione]zinc complex is obtained. The reaction scheme is as follows: JPEG0007798278000003.jpg71158

[0021] In the present invention, "room temperature" means a temperature in the range of 25±5°C. The present invention also provides the above-mentioned Zinc pentathiocenium and an agriculturally acceptable adjuvant or fungicide.

[0022] Preferably, the formulation of the composition is selected from suspensions (SC), emulsifiable concentrates (EC), dusts (DP), granules (GR), solutions (AS), ultra-low volume sprays (ULV), microcapsules (MC), smoke (FU), water emulsions (EW), and water-dispersible granules (WG).

[0023] The powders include wettable powders (WP) and soluble powders (SP).

[0024] In the field Zinc pentathiocenium Alternatively, when using a composition containing this, it is diluted with water to a concentration of 200 to 800 μg / mL and sprayed onto the leaves of plants.

[0025] The present invention Zinc pentathioceniumAlternatively, a composition containing the same has a good control effect against bacterial diseases of agricultural crops, particularly rice bacterial leaf blight, rice bacterial streak, citrus canker, citrus yellow dragon disease, tomato bacterial wilt, tobacco bacterial wilt, peach hole disease, cabbage black rot, Chinese cabbage soft rot, melon bacterial angular spot, and watermelon bacterial fruit rot.

[0026] the above Zinc pentathiocenium Alternatively, a composition containing the same can be used in the production of a pharmaceutical for controlling bacterial plant diseases, such as rice bacterial leaf blight, rice bacterial streak, citrus canker, citrus yellow dragon disease, tomato bacterial wilt, tobacco bacterial wilt, peach hole disease, cabbage black rot, Chinese cabbage soft rot, melon bacterial angular spot, and watermelon bacterial fruit rot. [Effects of the Invention]

[0027] The present invention has a clear antibacterial effect compared to the existing technology. As is clear from the above technical means, the present invention is based on the 5,11,17-trithia-1,3,7,9,13,15,19,20,21-nonazatria ring [14.2.1.1 4,7 .1 10,13 ]henicosa-4(20),10(21),16(19)-triene-6,12,18-trithione (X5) was used as a starting material to synthesize a novel metal complex, "chloro-bis[5,11,17-trithia-1,3,7,9,13,15,19,20,21-nonazatria[14.2.1.1 4,7 .1 10,13 ]heneicosa-4(20),10(21),16(19)-triene-6,12,18-trithione]zinc complex (pentathiocenium zinc)" has been synthesized and is effective against the above-mentioned plant bacterial diseases.

[0028] The chloro-bis[5,11,17-trithia-1,3,7,9,13,15,19,20,21-nonazatria ring [14.2.1.1 4,7 .1 10,13]henicosa-4(20),10(21),16(19)-triene-6,12,18-trithione]zinc (pentathiocenium zinc) manufacturing method and application, the raw material X5 (5,11,17-trithia-1,3,7,9,13,15,19,20,21-nonazatria ring [14.2.1.1 4,7 .1 10,13 ] Henicosa-4(20),10(21),16(19)-triene-6,12,18-trithione) is readily available and can be prepared in-house or obtained commercially. [Brief explanation of the drawings]

[0029] In order to more clearly describe the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the necessary drawings. [Figure 1] is the chemical structure of zinc pentathiocenium. [Figure 2] FIG. 1 shows the crystal structure and CDCC number of zinc pentathiocenium. [Figure 3] 1 is a diagram showing the infrared absorption spectrum of zinc pentathiocenium. [Figure 4] is a high-performance liquid chromatogram of the intermediate 5,11,17-trithia-1,3,7,9,13,15,19,20,21-nonazatriacyclyl[14.2.1.14,7.110,13]heneicosa-4(20),10(21),16(19)-triene-6,12,18-trithione. [Figure 5] is a 1H-NMR spectrum of the intermediate. [Figure 6] is a 13C-NMR spectrum of the intermediate. [Figure 7] 1 is a high-resolution mass spectrum of the intermediate. [Figure 8] FIG. 1 shows the crystal structure and CDCC number of the intermediate. [Figure 9] FIG. 1 shows the preventive and curative activity of zinc pentathiocenium against rice bacterial leaf blight at a concentration of 200 μg / mL. [Figure 10]1 shows the activity against rice bacterial streak under the same conditions. [Figure 11] 1 shows the preventive activity of zinc pentathiocenium against rice bacterial leaf blight in a greenhouse field experiment. [Figure 12] 1 is a particle size distribution diagram for a 20% zinc pentathiocenium suspension. [Figure 13] 1 is a particle size distribution table for the suspension. DETAILED DESCRIPTION OF THE INVENTION

[0030] The present invention will be described in more detail below with reference to examples. Example 1: 5,11,17-trithia-1,3,7,9,13,15,19,20,21-nonazatria ring [14.2.1.1 4,7 .1 10,13 ] Preparation of Henicosa-4(20), 10(21), 16(19)-triene-6,12,18-trithione (X5) (Synthesis of Intermediate X5) 2-Amino-5-thio-1,3,4-pentathiocenium (5 g, 37.54 mmol) was used as the starting material. The solution was completely dissolved in ethanol by heating and stirring, then cooled to 30°C. Formaldehyde or paraformaldehyde solution was gradually added, and the mixture was allowed to react at room temperature (25±5°C) for 1-2 hours. The precipitated solid was then recrystallized by adding dilute hydrochloric acid, which was then vacuum filtered and dried under suction. The solid was then dried at 50-70°C and recrystallized to obtain intermediate X5 (chemical name omitted). The yield was 8.73 g, with a melting point of over 250°C, a purity of 93-95%, and a yield of 51.40%. 1H NMR (400mHz, DMSO-d6) δ 8.77 (t, J=6.9 Hz, 3H), 5.43 (d, J=6.9 Hz, 6H), 13C NMR (100mHz, DMSO-d6) δ 181.42 (s, 2C), 155.28 (s, 2C), 57.14 (s, 2C). HRMS (ESI): C9H9N9S6[MH]+ calcd for 433.92214, found 433.92340.

[0031] X-ray single crystal structure analysis was carried out using a single crystal of intermediate X5 (Figure 3) obtained by slowly evaporating the DMSO / ether mixed solution at room temperature (25±5°C). JPEG0007798278000004.jpg53170 Crystallographic data for compound X5 have been deposited at the Cambridge Crystallographic Data Centre (CCDC: 2441750).

[0032] Example 2: Chloro-bis[5,11,17-trithia-1,3,7,9,13,15,19,20,21-nonazatetracycle[14.2.1.1 4,7 .1 10,13 ]Henicosa-4(20),10(21),16(19)-triene-6,12,18-trithione]zinc complex (Busaiquin zinc) (production of pentathiocenium zinc) Using intermediate X5 as the raw material, water is added as a solvent, NaOH is added as an acid scavenger, and then zinc chloride dissolved in water is added to the reaction system. After reacting for 1-2 hours at room temperature (25±5°C), water is added and the precipitated solid is filtered and dried to obtain the desired product. Zinc pentathiocenium The melting point is over 250℃, the content is 93-98%, and the yield is 91.78%.

[0033] The following data were obtained from a single crystal (Figure 2) obtained by reacting intermediate X5 with zinc chloride under high-temperature conditions. JPEG0007798278000005.jpg52170 Crystal structure data has been deposited at the Cambridge Crystallographic Data Centre (CCDC) and has the CCDC number 2449701.

[0034] The pentathiocenium zinc compound drug substance according to the present invention is a white powder, and the mass percentage of pentathiocenium zinc is 1 to 97%, preferably 10 to 80%.

[0035] The following shows the details of a comparative test on the control of rice bacterial leaf blight and rice bacterial streak using pentathiocenium zinc, thiazinyl copper, and thiazol zinc.

[0036] Example 3: Preparation of 10-20% wettable powder or suspension The drug substance obtained in Example 2 is ground and mixed with china clay and a wetting dispersant to obtain a 10-20% wettable powder or suspension. When in use, it is diluted with water to a concentration of 200-400 μg / mL and sprayed on the leaves of plants.

[0037] Test Example 1: The indoor inhibitory activity of the target compounds against bacterial leaf blight of rice, bacterial streak of rice, bacterial wilt of tomato, citrus canker, peach hole, cabbage black rot, bacterial wilt of tobacco, Chinese cabbage soft rot, melon angular spot, and watermelon fruit rot is shown in Tables 1 to 10.

[0038] The synthesized target compound, chloride-bis[5,11,17-trithia-1,3,7,9,13,15,19,20,21-nonazatetracycle[14.2.1.1 4,7 .1 10,13 [Henicosa-4(20),10(21),16(19)-triene-6,12,18-trithione]zinc complex (pentathiocenium zinc) was used with thiazinyl copper and thiazol zinc to prepare NB liquid medium containing the drug at concentrations of 100 and 50 μg / mL. 40 μL of bacterial suspension of Xanthomonas oryzae (Xoo) or Xoc (Xoc) was added to the prepared NB liquid medium and incubated at 28°C and 180 rpm for 24–48 hours. After the bacteria entered the logarithmic growth phase, the OD values ​​(OD595) of the bacterial suspensions at each concentration were measured using an enzyme-labeled analyzer.

[0039] In addition, the OD values ​​(OD595) of sterile NB liquid medium containing the target compound and control drug at concentrations of 100 and 50 μg / mL were also measured, and the OD values ​​of the medium itself were corrected. The corrected OD values ​​and the inhibition rate were calculated using the following formulas:

[0040] Corrected OD value = OD value of bacteria-containing medium - OD value of sterile medium Inhibition rate (%) = (OD value of control culture medium after calibration - OD value of poison-containing culture medium after calibration) / OD value of control culture medium after calibration x 100

[0041] Five concentration gradients were set for the target compound, and the EC values ​​at each concentration were measured against bacterial leaf blight of rice (Xoo), bacterial streak of rice (Xoc), bacterial wilt of tomato, bacterial canker of citrus (Xac), bacterial hole of peach, cabbage black rot, bacterial wilt of tobacco, soft rot of Chinese cabbage, bacterial angular spot of melon, and bacterial fruit rot of watermelon. 50 The value (50% effective concentration) was measured.

[0042] By the above method, the chloro-bis[5,11,17-trithia-1,3,7,9,13,15,19,20,21-nonazatria ring [14.2.1.1 4,7 .1 10,13 Antibacterial activity and EC of ]heneicosa-4(20),10(21),16(19)-triene-6,12,18-trithione]zinc complex (pentathiocenium zinc) 50 The values ​​were measured, and the results are shown in Tables 1 to 10.

[0043] Table 1. Antibacterial activity of the fungicide pentathiocenium zinc of the present invention against Xanthomonas oryzae pv. oryzae JPEG0007798278000006.jpg67170Note: a Average value of three replicates. b Commercially available antibacterial agent (20%, suspension).

[0044] As is clear from the results in Table 1, the fungicides of the present invention, pentathiocenium zinc, thiazole zinc and tiadinil copper, all have a certain level of antibacterial activity against Xanthomonas oryzae pv. oryzae, and their EC 50 The concentrations were 21.31, 23.96, and 82.64 μg / mL. Among these, zinc pentathiocenium (21.31 μg / mL) showed excellent antibacterial activity, superior to commercially available drugs such as zinc thiazol (23.96 μg / mL) and copper tiadinil (82.64 μg / mL).

[0045] Table 2. Antibacterial activity of the fungicide pentathiocenium zinc of the present invention against rice bacterial streak pathogen JPEG0007798278000007.jpg40170Note: a Average value of three replicates. b Commercially available antibacterial agent (20%, suspension).

[0046] As is clear from the results in Table 2, the fungicides of the present invention, pentathiocenium zinc, thiazotin zinc and tiadinil copper, have a certain level of antibacterial activity against bacterial streak pathogens, and their EC 50 The antifungal activity of the fungicide of the present invention, zinc pentathiocenium (34.11 μg / mL), against rice bacterial streak fungus was superior to that of the commercially available fungicides thiazotin zinc (37.74 μg / mL) and tiadinil copper (87.08 μg / mL).

[0047] Table 3. Antibacterial activity of the fungicide of the present invention, zinc pentathiocenium, against bacterial wilt of tomato JPEG0007798278000008.jpg74170Note: a Average value of three replicates. b Commercially available antibacterial agent (20%, suspension).

[0048] As is clear from the results in Table 3, the fungicides of the present invention, i.e., pentathiocenium zinc, thiazotin zinc and tiadinil copper, have a certain level of antibacterial activity against bacterial wilt of tomato, and their EC 50 The antibacterial activities of the fungicides of the present invention, pentathiocenium zinc (38.49 μg / mL), against the tomato bacterial wilt fungus were 38.49, 37.95, and 130.63 μg / mL, respectively. Among them, the fungicide pentathiocenium zinc (38.49 μg / mL) of the present invention showed good antibacterial activity against the tomato bacterial wilt fungus, being superior to tiadinil copper (130.63 μg / mL) and equivalent to the commercially available fungicide thiazotin zinc (37.95 μg / mL).

[0049] Table 4. Antibacterial activity of zinc pentathiocenium, the fungicide of the present invention, against Xanthomonas campestris pv. citri JPEG0007798278000009.jpg74170Note: a Average value of three replicates.b Commercially available antibacterial agent (20%, suspension).

[0050] As is clear from the results in Table 4, the fungicides of the present invention, i.e., pentathiocenium zinc, thiazotin zinc and tiadinil copper, have a certain level of antibacterial activity against Xanthomonas campestris pv. citri, and their EC 50 The antibacterial activities of the fungicides of the present invention, zinc pentathiocenium (44.59 μg / mL), against Xanthomonas campestris pv. citri were 44.59, 45.05, and 87.74 μg / mL, respectively. Among these, the fungicide pentathiocenium zinc (44.59 μg / mL) of the present invention showed excellent antibacterial activity against Xanthomonas campestris pv. citri, and was superior to the commercially available fungicides thiazotin zinc (45.05 μg / mL) and tiadinil copper (87.74 μg / mL).

[0051] Table 5. Antibacterial activity of the fungicide of the present invention, zinc pentathiocenium, against peach borer fungus JPEG0007798278000010.jpg74170Note: a Average value of three replicates. b Commercially available antibacterial agent (20%, suspension).

[0052] As is clear from the results in Table 5, the fungicides of the present invention, i.e., pentathiocenium zinc, thiazotin zinc and tiadinil copper, have a certain level of antibacterial activity against peach borer, and their EC 50 The antifungal activities of the fungicides of the present invention, zinc pentathiocenium (37.37 μg / mL), against peach borer fungus were 37.37, 39.39, and 244.76 μg / mL, respectively. Among them, the fungicide pentathiocenium zinc (37.37 μg / mL) of the present invention showed excellent antifungal activity against peach borer fungus, and was superior to the commercially available fungicides thiazotin zinc (39.39 μg / mL) and tiadinil copper (244.76 μg / mL).

[0053] Table 6. Antibacterial activity of zinc pentathiocenium, the fungicide of the present invention, against Black Rot Fungus of Cabbage JPEG0007798278000011.jpg74170Note: a Average value of three replicates. b Commercially available antibacterial agent (20%, suspension).

[0054] As is clear from the results in Table 6, the fungicides of the present invention, i.e., pentathiocenium zinc, thiazotin zinc and tiadinil copper, have a certain antibacterial activity against the cabbage black rot fungus, and their EC 50 were 49.19, 84.45, and 207.51 μg / mL, respectively. Among them, the fungicide of the present invention, pentathiocenium zinc (49.19 μg / mL), had a certain antibacterial activity against the cabbage black rot fungus, and was superior to the commercially available fungicides tiadinil copper (207.51 μg / mL) and thiazotin zinc (84.45 μg / mL).

[0055] Table 7. Antibacterial activity of zinc pentathiocenium, a fungicide of the present invention, against tobacco bacterial wilt fungus JPEG0007798278000012.jpg75170Note: a Average value of three replicates. b Commercially available antibacterial agent (20%, suspension).

[0056] As is clear from the results in Table 7, the fungicides of the present invention, i.e., pentathiocenium zinc, thiazotin zinc and tiadinil copper, have a certain level of antibacterial activity against the tobacco bacterial wilt pathogen, and their EC 50 The antibacterial activities of the fungicide of the present invention, pentathiocenium zinc (86.63 μg / mL), against the tobacco bacterial wilt fungus were superior to those of the commercially available fungicide tiadinil copper (190.44 μg / mL), and were equivalent to those of thiazotin zinc (87.99 μg / mL).

[0057] Table 8. Antibacterial activity of the fungicide of the present invention, zinc pentathiocenium, against the soft rot fungus of Chinese cabbage JPEG0007798278000013.jpg75170Note: a Average value of three replicates. b Commercially available antibacterial agent (20%, suspension).

[0058] As is clear from the results in Table 8, the fungicides of the present invention, i.e., pentathiocenium zinc, thiazotin zinc and tiadinil copper, have a certain antibacterial activity against the soft rot fungus of Chinese cabbage, and their EC 50 The antibacterial activities of the fungicide of the present invention, pentathiocenium zinc (38.59 μg / mL), against the Chinese cabbage soft rot fungus were superior to those of the commercially available fungicides tiadinil copper (158.94 μg / mL) and thiazotin zinc (39.88 μg / mL).

[0059] Table 9. Antibacterial activity of the fungicide of the present invention, zinc pentathiocenium, against bacterial angular spot of melon JPEG0007798278000014.jpg75170Note: a Average value of three replicates. b Commercially available antibacterial agent (20%, suspension).

[0060] As is clear from the results in Table 9, the fungicides of the present invention, i.e., pentathiocenium zinc, thiazotin zinc and tiadinil copper, have a certain level of antibacterial activity against the bacterial angular spot pathogen of melon, and their EC 50 The antifungal activities of the fungicide of the present invention, zinc pentathiocenium (24.45 μg / mL), against the bacterial angular spot fungus of melon were superior to those of the commercially available fungicides tiadinil copper (90.80 μg / mL) and thiazotin zinc (31.57 μg / mL).

[0061] Table 10. Antibacterial activity of the fungicide of the present invention, zinc pentathiocenium, against bacterial fruit rot bacteria of watermelon JPEG0007798278000015.jpg74170Note: a Average value of three replicates. b Commercially available antibacterial agent (20%, suspension).

[0062] As is clear from the results in Table 10, the fungicides of the present invention, i.e., pentathiocenium zinc, thiazotin zinc and tiadinil copper, have a certain antibacterial activity against the bacterial fruit rot bacteria of watermelon, and their EC 50 The antibacterial activities of the fungicide of the present invention, zinc pentathiocenium (38.47 μg / mL), against the bacterial fruit rot fungus of watermelon were superior to those of the commercially available fungicides tiadinil copper (107.58 μg / mL) and thiazotin zinc (93.51 μg / mL).

[0063] Test Example 2 The fungicide of the present invention, chloro-bis[5,11,17-trithia-1,3,7,9,13,15,19,20,21-nine-tetracyclo[14.2.1.1 4,7 .1 10,13 A comparative study was conducted using ]heneicosa-4(20),10(21),16(19)-triene-6,12,18-trithione]zinc (pentathiocenium zinc) with thiazinyl copper and thiazotin zinc to further clarify their effectiveness in controlling rice bacterial leaf blight and rice bacterial streak. The details of the comparative study are as follows:

[0064] 1. Testing the preventive and curative effects of the fungicide pentathiocenium zinc of the present invention against rice leaf blight in live pot cultivation The leaf cutting method was used to measure the preventive and curative effects of pentathiocenium zinc, the fungicide of the present invention, on rice bacterial leaf blight in live pot cultivation when treated at a concentration of 200 μg / mL.

[0065] 1.1 Preventive activity The fungicides of the present invention, pentathiocenium zinc, tiadinil copper, and thiazotin zinc, were each dissolved in 200 μL of DMSO and then diluted with 0.1% Tween-80 to a concentration of 200 μg / mL. This solution was sprayed evenly onto rice leaves until droplets formed. 24 hours after treatment, the leaves were inoculated at the tip of one-third of the leaf using scissors containing the bacterial leaf blight pathogen. The fungal solution was inoculated at the tip of one-third of the leaf, and clean water without any fungicide was used as a control. Each treatment was performed using 10 to 15 leaf pieces, and three replicates were performed. 14 days after treatment, the lesion length on the rice leaf pieces was measured, and the control efficacy was calculated based on the lesion length.

[0066] 1.2 Therapeutic activity A 2-3 cm section from the tip of each rice leaf disc was removed using scissors coated with a pathogen solution. 24 hours later, the fungicides of the present invention, zinc pentathiocenium, zinc thiazotin, and copper tiadinil, were dissolved in DMSO and diluted with 0.1% Tween-80 to a concentration of 200 μg / mL. This solution was sprayed evenly onto the rice leaf discs until droplets formed. A control group was treated with clean water without any chemicals. Ten to fifteen leaf discs were treated for each rice plant. Fourteen days after treatment, the lesion lengths on the rice leaf discs were measured, and the control efficacy was calculated based on the lesion lengths.

[0067] 2. Testing the preventive and curative effects of the fungicide pentathiocenium zinc of the present invention against rice bacterial streak disease in a live pot cultivation test Using the pressure infiltration method, the preventive and curative effects of pentathiocenium zinc, the fungicide of the present invention, on rice bacterial streak disease in live pot cultivation were measured when treated at a concentration of 200 μg / mL.

[0068] 2.1 Preventive activity The fungicides of the present invention, pentathiocenium zinc, tiadinil copper, and thiazotin zinc, were each dissolved in 200 μL of DMSO and then diluted with 0.1% Tween-80 solution to a concentration of 200 μg / mL. This solution was sprayed evenly onto rice leaves until droplets formed. 24 hours after treatment, pressure inoculation was performed using a metered syringe containing the rice bacterial streak pathogen, with the inoculation site being 1 / 3 to 1 / 2 of the leaf tip of the rice leaf disc. A control group was treated with clean water without any fungicide. Each treatment was performed using 10 to 15 leaf discs, and three replicates were performed. 14 days after treatment, the lesion lengths on the rice leaf discs were measured, and the control efficacy was calculated based on the lesion lengths.

[0069] 2.2 Therapeutic activity Using a metered syringe loaded with the rice bacterial streak fungus, pressure inoculation was performed on rice leaf discs at the leaf tip 1 / 3 to 1 / 2 of the way. 24 hours after inoculation, the fungicides of the present invention, pentathiocenium zinc, tiadinil copper, and thiazotin zinc, were each dissolved in DMSO and prepared in a 0.1% Tween-80 solution at a concentration of 200 μg / mL. This solution was sprayed evenly onto the rice leaf discs until droplets formed. A control group was treated with clean water without any fungicide. Ten to fifteen leaf discs were treated for each rice plant. Fourteen days after treatment, the lesion lengths on the rice leaf discs were measured, and the control efficacy was calculated based on the lesion lengths.

[0070] Table 11. Preventive activity of the fungicide of the present invention, pentathiocenium zinc, against rice leaf blight JPEG0007798278000016.jpg92152Note 1: The fungicide of this invention, pentathiocenium zinc, is the active ingredient, thiazotin zinc is a suspension containing 20% ​​of the active ingredient, and tiadinil copper is a suspension containing 20% ​​of the active ingredient.

[0071] Note 2: The control effect was investigated 14 days after application. As can be seen from Table 11, at a concentration of 200 μg / mL, the preventive effects of the fungicides of the present invention, pentathiocenium zinc, thiazotin zinc and tiadinil copper, against rice bacterial leaf blight were 80.98%, 70.83% and 53.81%, respectively.

[0072] Among them, the fungicide of the present invention, pentathiocenium zinc, showed excellent preventive effect against rice bacterial leaf blight, being more than 10 points higher than the commercially available fungicide thiazotin zinc (70.83%) and more than 20 points higher than the commercially available fungicide tiadinil copper (53.81%).

[0073] Table 12. Therapeutic activity of the fungicide of the present invention, pentathiocenium zinc, against rice leaf blight JPEG0007798278000017.jpg93153Note 1: The fungicide of this invention, pentathiocenium zinc, is the active ingredient, thiazotin zinc is a suspension containing 20% ​​of the active ingredient, and tiadinil copper is a suspension containing 20% ​​of the active ingredient. Note 2: The control effect was investigated 14 days after application.

[0074] Note 3: If different lowercase letters are placed after data in the same column, it indicates a significant difference (p<0.05).

[0075] As can be seen from Table 12, at a concentration of 200 μg / mL, the curative effects of the fungicides of the present invention, pentathiocenium zinc, thiazotin zinc, and tiadinil copper, against rice bacterial leaf blight were 78.34%, 69.11%, and 50.57%, respectively.

[0076] Among them, the fungicide of the present invention, pentathiocenium zinc, showed good curative effect against rice bacterial leaf blight (78.34%), which was superior to commercially available drugs, thiazotin zinc (69.11%) and tiadinil copper (50.57%).

[0077] As can be seen from Tables 11 and 12 above, the fungicide of the present invention, pentathiocenium zinc, has excellent curative and preventive effects against rice leaf blight, proving that the fungicide of the present invention has an extremely high fungicidal effect.

[0078] Table 13. Preventive activity of the fungicide of the present invention, pentathiocenium zinc, against rice bacterial streak disease JPEG0007798278000018.jpg94153Note 1: The fungicide of this invention, pentathiocenium zinc, is the active ingredient, thiazotin zinc is a suspension containing 20% ​​of the active ingredient, and tiadinil copper is a suspension containing 20% ​​of the active ingredient. Note 2: The control effect was investigated 14 days after application. Note 3: If different lowercase letters are placed after data in the same column, it indicates a significant difference (p<0.05).

[0079] As can be seen from Table 13, at a concentration of 200 μg / mL, the preventive effects of the fungicides of the present invention, pentathiocenium zinc, thiazotin zinc and tiadinil copper, against rice bacterial streak disease were 67.00%, 56.98% and 49.12%, respectively.

[0080] Among them, the fungicide of the present invention, pentathiocenium zinc (67.00%), showed excellent preventive effect against rice bacterial streak disease, and was superior to the commercially available fungicides thiazotin zinc (56.98%) and tiadinil copper (49.12%).

[0081] Table 14. Therapeutic activity of the fungicide pentathiocenium zinc of the present invention against rice bacterial streak disease JPEG0007798278000019.jpg93150Note 1: The fungicide of this invention, pentathiocenium zinc, is the active ingredient, thiazotin zinc is a suspension containing 20% ​​of the active ingredient, and tiadinil copper is a suspension containing 20% ​​of the active ingredient. Note 2: The control effect was investigated 14 days after application.

[0082] Note 3: If different lowercase letters are placed after data in the same column, it indicates a significant difference (p<0.05).

[0083] As can be seen from Table 14, at a concentration of 200 μg / mL, the fungicides of the present invention, pentathiocenium zinc, thiazotin zinc and tiadinil copper, had a certain therapeutic effect against rice bacterial streak disease, with the therapeutic effects being 65.18%, 55.82% and 47.14%, respectively.

[0084] Among them, the fungicide of the present invention, pentathiocenium zinc (65.18%), showed a superior therapeutic effect against rice bacterial streak disease to the commercially available drugs thiazotin zinc (55.82%) and tiadinil copper (47.14%).

[0085] Test Example 3: Bioprotection effect test of the fungicide pentathiocenium zinc of the present invention against rice bacterial leaf blight in a greenhouse field The test procedure was the same as that used when the protective effect of the fungicide pentathiocenium zinc of the present invention against bacterial leaf blight of rice was measured by the leaf cutting method at a concentration of 200 μg / mL.

[0086] Table 15. Bioprotection efficacy test of the fungicide pentathiocenium zinc of the present invention against rice bacterial leaf blight in a greenhouse field JPEG0007798278000020.jpg77148

[0087] Note 1: The fungicide of this invention, pentathiocenium zinc, is the active ingredient, thiazotin zinc is a 20% suspension, and tiadinil copper is a 20% suspension. Note 2: The control effect was investigated 14 days after application. Note 3: If data in the same column are followed by different lowercase letters, it indicates a significant difference (p<0.05).

[0088] As can be seen from Table 15, when the bioprotection efficacy tests were conducted in a greenhouse field on the fungicides of the present invention, pentathiocenium zinc and thiazotin zinc, at a concentration of 200 μg / mL, the protective efficacy was 73.15% and 57.92%, respectively.

[0089] Among them, the fungicide of the present invention, pentathiocenium zinc, had a good protective effect against rice leaf blight, and was superior to the commercially available fungicide, thiazotin zinc (57.92%).

[0090] Results and Discussion: As can be seen from the above data, the results of the greenhouse potted plant testing further prove that, at the same concentration, the control effect of the fungicide of the present invention, pentathiocenium zinc, against rice bacterial leaf blight is 15 to 20 points higher than that of the tiadinil copper fungicide (Ron blight) disclosed in CN1227224A, and more than 10 points higher than that of the commercially available agent, thiazotin zinc.

[0091] Therefore, it is clear that the fungicide pentathiocenium zinc of the present invention has a very good control effect against rice bacterial leaf blight and rice bacterial streak.

[0092] To further evaluate the fungicidal activity of the fungicide pentathiocenium zinc of the present invention, it is necessary to formulate pentathiocenium zinc into a 20% suspension and conduct field trials to disseminate the results and provide data for the pesticide registration of pentathiocenium zinc.

[0093] In order to solve the above problems existing in the current technology, the present invention provides a formulation for preparing a 5-25% aqueous suspension of zinc pentathiocenium.

[0094] This formulation contains the active ingredient pentathiocenium zinc, a wetting and dispersing agent, a thickener, an antifreeze agent, an antifoaming agent, and water, with the weight ratios of each ingredient being 5-25 wt%, 3-12 wt%, 0.5-2.5 wt%, 2-6 wt%, and 0.3-0.5 wt%, respectively, and the total is adjusted to 100% with water.

[0095] Preferably, the weight ratio of zinc pentathiocenium is 5 to 25 wt%, 5 to 20 wt%, 5 to 10 wt%, 10 to 20 wt%, or 10 to 25 wt%, and most preferably 20 wt%.

[0096] The wetting and dispersing agents selected herein are complexes of ionic or nonionic adjuvants, including polymeric amphiphilic anionic and nonionic surfactant complexes, phosphate esters, lignin sulfonates, salts of phenolsulfonic acid or naphthalenesulfonic acid, salts of polyacrylic acid, sulfosuccinates, alkyl sulfonates, alkylaryl sulfonates, alkyl sulfates, lauryl ether sulfates, fatty alcohol sulfates, sulfonate formaldehyde condensates, and sulfated hexadecanol, heptadecanol, and octadecanol, as well as sulfated fatty alcohol ethylene glycol ethers.

[0097] The antifoaming agent is 0.3-0.5 wt% of polydimethylsiloxane, an organosilicon antifoaming agent.

[0098] Antifreeze agents are inorganic salts. The thickening agent is either magnesium aluminum silicate SF-40, xanthan gum, or both.

[0099] A preferred wetting and dispersing agent is composed of a polymeric amphiphilic anionic / nonionic surfactant complex SC29, sodium diphenylmethanesulfonate HAS040, naphthalenesulfonic acid sodium salt formaldehyde condensate NNO, and one of sodium p-toluenesulfonate, sodium methanesulfonate, or polynaphthaleneformaldehydesulfonic acid sodium salt in a weight ratio of 2:2:2:1.5.

[0100] More preferred is a composition comprising polymeric amphiphilic anionic / nonionic surfactant complex SC29, sodium diphenylmethanesulfonate HAS040, sodium naphthalenesulfonate formaldehyde condensate NNO and sodium p-toluenesulfonate in a weight ratio of 2:2:2:1.5.

[0101] A preferred thickening agent is 2% magnesium aluminum silicate SF-40 or a blend of 1% magnesium aluminum silicate and 0.05% xanthan gum.

[0102] The pentathiocenium zinc suspension for controlling plant bacterial diseases is prepared by mixing a wetting and dispersing agent, an antifreeze agent and water in the weight percentages specified above, dissolving them by stirring, then adding pentathiocenium zinc and a thickener in the weight percentages specified above, and mixing them uniformly under the action of a shearing machine. The mixed slurry is then pumped to a sand mill for polishing.

[0103] Add the organosilicon antifoaming agent in the weight percentage, measure the particle size every hour, and when D90 reaches approximately 6.0 μm, stop stirring and filter to obtain a 20% pentathiocenium zinc suspension.

[0104] The particle size D90 of this suspension is 5 to 8 μm. Innovations of this patent: The main significance of the developed formulation is to solve the problem of improving the control effect of the active ingredients in pentathiocenium zinc suspensions and pentathiocenium zinc wettable powders against bacterial plant diseases by extensively screening wetting and dispersing agents.

[0105] The pentathiocenium zinc suspension prepared by the present invention has the characteristics of being well dispersible in water and being advantageous in terms of the stability of the active ingredient during storage.

[0106] 1. Screening of wetting and dispersing agents A polymeric amphiphilic anionic / nonionic surfactant complex was compounded with different types of surfactants, and the water dispersibility of the active ingredient and the decomposition rate of the active ingredient after thermal storage were measured for 5-25% pentathiocenium zinc suspensions prepared using this compound.

[0107] The specific results are shown in Table 16. Table 16. Selection of wetting and dispersing agents JPEG0007798278000021.jpg124170

[0108] As shown in the results in Table 16, when different types of auxiliary agents were screened, it was found that the addition of sulfonate-based auxiliary agents was advantageous for the stability of the active ingredient.

[0109] Pentathiocenium zinc suspensions containing polymeric amphiphilic anionic / nonionic surfactant complex SC29, sodium diphenylmethanesulfonate HAS040, formalin condensate of sodium naphthalenesulfonate NNO, and sodium p-toluenesulfonate, sodium methanesulfonate, or polynaphthaleneformaldehydesulfonate sodium salt exhibited good dispersibility and were able to suppress the decomposition rate of the active ingredient after thermal storage to within 5%.

[0110] In order to screen for the optimal amounts of auxiliary agents such as sodium p-toluenesulfonate, polynaphthaleneformaldehydesulfonic acid sodium salt, and sodium methanesulfonate, three different contents of 0.5%, 1.5%, and 3.0% were set and screening was carried out.

[0111] The specific results are shown in Table 17. Table 17 Screening of auxiliary agent usage JPEG0007798278000022.jpg183170 As shown in the results in Table 17, the decomposition rate of zinc pentathiocenium after thermal storage was less than 5% at all three different contents.

[0112] Sodium methanesulfonate is relatively expensive and generally dispersible in water.

[0113] Addition of polynaphthalene formalin sulfonic acid sodium salt will cause the suspension to turn yellow, affecting its appearance.

[0114] On the other hand, the addition of sodium p-toluenesulfonate not only improves the stability of the active ingredient, but also makes the price relatively low and the appearance of the suspension relatively good.

[0115] Therefore, taking into consideration the cost and properties, the optimal wetting and dispersing agent formulation was SC29:HAS040:NNO:sodium p-toluenesulfonate=2:2:1:1.5.

[0116] 2. Screening of thickeners Aqueous suspensions often have problems with physical stability during storage, such as particle size increase due to particle aggregation, settling and water separation, and thickening and caking.

[0117] The above formulation is prone to sedimentation and water separation during long-term storage.

[0118] In this situation, sedimentation stability can be improved by increasing the viscosity.

[0119] However, if the viscosity is too high, the product will be difficult to pour and will adhere to the walls of the container, hindering processing, production, and use.

[0120] The appropriate viscosity provides the formulation with good stability and high suspension rate.

[0121] In this experiment, based on the relevant theory and considering the unstable chemical properties of zinc pentathiocenium, the types of auxiliary agents required in the previously screened formulation were not changed. The viscosity was varied by screening the amounts of magnesium aluminum silicate and xanthan gum used.

[0122] However, since an increase in viscosity may reduce the auto-dispersibility of the aqueous suspension, the amount of dispersant NNO used was increased to improve the auto-dispersibility in water.

[0123] The specific results are shown in Table 18. Table 18. Thickener screening JPEG0007798278000023.jpg86170As shown in Table 18, the addition of excessive xanthan gum has a certain effect on both the fluidity and water-dispersibility of the formulation system.

[0124] Therefore, in order to improve the settling stability under the condition that does not affect the water inlet dispersibility, 2% magnesium aluminum silicate was added as a thickener. Or select a combination of 1% magnesium aluminum silicate and 0.05% xanthan gum, Furthermore, increasing the NNO content improves the water dispersibility of the formulation.

[0125] 3. Select the amount of antifoam to use Most of the wetting and dispersing agents according to the present invention are sulfonates, which generate a large amount of bubbles during processing, which affects the polishing effect.

[0126] For this reason, an appropriate amount of an organic silicone antifoaming agent such as polydimethylsiloxane is usually added to the suspension.

[0127] However, the amount of antifoaming agent added must be appropriate; if it is added in excess, the surface tension of the system will decrease, making the phase separation phenomenon more pronounced.

[0128] If too little is added, the defoaming effect is not significant.

[0129] In this test, a general-purpose organic silicone antifoaming agent was selected and tested.

[0130] The specific results are shown in Table 19. Table 19 Screening of antifoam usage JPEG0007798278000024.jpg63152As shown in Table 19, if the amount of antifoaming agent used is small, it is not possible to effectively eliminate the large amount of bubbles that are generated during the polishing process.

[0131] When the amount used is controlled to 0.3 to 0.5%, the amount of bubbles generated during the manufacturing process is relatively small, which is advantageous for polishing.

[0132] 4. Selection of antifreeze agent Pesticide suspensions that use water as a dispersion medium must maintain stability even under extremely cold, low-temperature conditions during storage, and usually require the addition of a certain amount of an appropriate antifreeze agent.

[0133] When glycerin is used as an antifreeze agent, the viscosity of the system increases and the fluidity deteriorates.

[0134] When ethylene glycol is used as a cryoprotectant, the stability and flowability of the formulation are good, but the decomposition rate of the drug substance tends to be high after heat storage.

[0135] When sodium chloride is selected as the cryoprotectant, a small amount of precipitate will form at the bottom after cold storage, but the degree of degradation of the drug substance will not increase.

[0136] Therefore, sodium chloride is the most suitable antifreeze agent.

[0137] 5. Effect of particle size on drug substance stability after thermal storage After determining the above auxiliary agents, aqueous suspensions of pentathiocenium zinc with different particle sizes (numbers 1 to 6) were prepared.

[0138] After heat storage, the content of the active ingredient was measured using the heat stability test method for pesticides GB / T19136-2003, and then the decomposition rate of the active ingredient after heat storage was calculated.

[0139] The specific results are shown in Table 20. Table 20. Effect of particle size on drug substance stability JPEG0007798278000025.jpg83150As shown in Figure 13 and Table 20, when the particle size of the 20% aqueous suspension of pentathiocenium zinc prepared using the above auxiliary agents is in the range of 5-8 μm, the stability requirement is met.

[0140] This indicates that the formulation and particle size have a significant effect on the chemical stability of the active ingredient in the zinc pentathiocenium aqueous suspension. The smaller the particle size, the better the chemical stability of the active ingredient, but if the particle size is too small, industrial production becomes difficult.

[0141] After selecting the moistening and dispersing agent, the amount of auxiliary agent used, the thickener, the amount of antifoaming agent used, and the antifreeze agent, the optimal formulation and manufacturing method were determined as shown in Table 21 below. Table 21. Formulation composition JPEG0007798278000026.jpg130170The above-mentioned pentathiocenium zinc suspension for controlling plant bacterial diseases is prepared by mixing a dispersant, a wetting agent, an antifreeze, and water according to the weight percentages, stirring to dissolve, then adding pentathiocenium zinc and a thickener according to the weight percentages and mixing uniformly under the action of a shear. The mixed slurry is then pumped to a sand mill for polishing, adding an organosilicon antifoaming agent according to the weight percentages, measuring the particle size every hour, and stopping stirring when the D90 reaches approximately 5.0 μm. The resulting suspension is a 20% pentathiocenium zinc suspension.

[0142] The particle size D90 of the suspension is 5 to 8 μm. 6. Control item index specifications for 20% pentathiocenium zinc suspension The main performance of the suspension was tested in accordance with the Chinese national standard requirements for pesticide suspensions (GB / T19136-2003), and the details are shown in Table 22. The results showed that with this formulation, the pentathiocenium zinc aqueous suspension exhibited a milky white, uniform dispersion system, with good dispersibility and suspension rate, and the drug substance was relatively stable after hot storage, even at low temperatures.

[0143] Table 22. Control item index for 20% pentathiocenium zinc aqueous suspension The present invention will be further described below by way of examples. It should be understood that the methods described in the examples are merely illustrative of the present invention and are not intended to limit the present invention. Under the concept of the present invention, any simple improvements made to the production method of the present invention are within the scope of protection claimed by the present invention. All raw materials and solvents used in the examples are commercially available products of corresponding purity.

[0144] Example 3: Preparation of 20% Zinc Pentathiocenium Suspension 2.0 g of sodium diphenylmethanesulfonate HAS040, 2.0 g of sodium naphthalenesulfonate formaldehyde condensate NNO, 1.5 g of sodium paratoluenesulfonate, 4.0 g of sodium chloride, and 2.0 g of polymeric amphiphilic anionic-nonionic surfactant complex SC29 were added to 66.1 g of secondary water in a beaker and stirred to dissolve. Then, 20.0 g of zinc pentathiocenium and 2.0 g of magnesium aluminum silicate were added and homogenized using a shear homogenizer. The mixture was then poured into a sand mill containing zirconia beads in a 1:1 volume / mass ratio, 0.4 g of polydimethylsiloxane was added, and the sand mill was started under an ice-water bath. The particle size is measured every hour, and after about 4 hours, the particle size is measured using a laser particle sizer. When the D90 reaches about 5 μm, stirring is stopped and the resulting suspension is filtered to obtain a 20% pentathiocenium zinc suspension.

[0145] Test Example 5: Field test of the efficacy of the fungicide pentathiocenium zinc of the present invention against rice bacterial leaf blight Test site address: Yangchang Township, Pingba District, Anshun City, Guizhou Province, People's Republic of China, National Crop Variety Measurement Station (Guizhou) Base, longitude 106.318371, latitude 26.367751, altitude 1,220 meters, test site is flat paddy field.

[0146] In this experiment, five treatments were set up, with four replications, for a total of 20 plots. The plot area was 5m x 4m = 20m. 2 .

[0147] Disease surveillance and outcome statistics During the test period, the disease condition was investigated twice, the first time before treatment to investigate the disease condition before the chemical treatment, and the second time 14 days after the last chemical treatment to investigate the control effect after the last chemical treatment.

[0148] In each plot, 50 plants were sampled at each diagonal point, and all flag leaves and the two leaves below the flag leaf were sampled. The leaves were graded based on the severity of lesions, and the total number of leaves and the number of diseased leaves in each grade were recorded.

[0149] Grading criteria for rice bacterial leaf blight: Grade 0: No lesions on leaves; Grade 1: Lesion area is 10% or less of the leaf area; Grade 3: Lesion area is 11-25% of the leaf area; Grade 5: Lesion area is 26-45% of the leaf area; Grade 7: Lesion area is 46-65% of leaf area; Grade 9: Lesion area is 65% or more of the leaf area.

[0150] The incidence rate and disease severity index were calculated according to the following formula, and significance tests were performed using SPSS software.

[0151] Disease index = [Σ(number of diseased leaves of each grade × relative grade value) / (total number of leaves surveyed × 9)] × 100 Control effect (%) = [(disease index of untreated control area - disease index of treated area) / disease index of untreated control area] x 100 Test results

[0152] Table 23. Field control effect of the fungicide pentathiocenium zinc of the present invention against rice bacterial leaf blight JPEG0007798278000028.jpg102170Note: Different lowercase letters after data in the same column indicate significant differences (p<0.05).

[0153] As shown in Table 23, the control efficacy of pentathiocenium zinc (50-150 mL / mu) increased significantly with increasing dosage. The disease index decreased year by year (1.18-0.97), and the control efficacy reached 64.69%-70.91%. The control efficacy was particularly good at 150 mL / mu (70.91%), which was superior to the control agent, 20% thiazole zinc (67.13%). Furthermore, safety to rice was confirmed within the concentration range used in this test, and no phytotoxicity occurred.

[0154] Test Example 6: Field test of the efficacy of the fungicide pentathiocenium zinc of the present invention against bacterial wilt of tomato Test site address: Guai'er Village, Jiu'an Township, Huaxi District, Guiyang City, Guizhou Province, People's Republic of China, latitude 26.515145°, longitude 106.575132°, altitude 1184.96m. The test site is flat and uniformly fertile, and is a tomato-tomato crop rotation area where bacterial wilt disease frequently occurs.

[0155] In this experiment, plots were set up based on the natural ridge plots for tomatoes, with a spacing of 0.33m between plants, 1m between rows, a plot length of 5m, and a plot width of 3m. 45 tomato seedlings were planted in each plot, and the plots were arranged in a randomized manner. In this experiment, five treatment plots were set up, with four replications, for a total of 20 plots. The plot area was 3.0m x 5.0m = 15m. 2 .

[0156] Disease surveillance and outcome statistics During the test period, the disease condition was investigated twice, the first time before treatment to investigate the disease condition before the chemical treatment, and the second time 21 days after the last chemical treatment to investigate the control effect after the last chemical treatment.

[0157] All plants in each subdivision were surveyed and the total number of plants and the number of diseased plants were recorded.

[0158] The incidence rate and disease severity index were calculated using the following formula, and significance tests were performed using SPSS software.

[0159] Diseased plant rate (%) = (number of diseased plants / total number of plants surveyed) x 100 Control effect (%) = [(ratio of diseased plants in untreated control area - ratio of diseased plants in treated area) / ratio of diseased plants in untreated control area] x 100

[0160] Test results Table 24. Field control effect of the fungicide pentathiocenium zinc of the present invention against bacterial wilt of tomato JPEG0007798278000029.jpg92170Note: Different lowercase letters after data in the same column indicate significant inferiority (p<0.05).

[0161] As shown in Table 24, the control effect of 20% pentathiocenium zinc suspension (50-150mL / mu) increased significantly with increasing dosage. At 150mL / mu, the control effect against bacterial wilt of tomato was the best (69.34%), superior to the control agent 20% thiazole zinc (68.19%). Furthermore, safety to tomatoes was confirmed within the range of concentrations used in this test, and no phytotoxicity occurred.

[0162] Currently, acute toxicity tests and toxicological tests of pentathiocenium zinc are being commissioned to Xishan Zhongke Drug Research Co., Ltd. Among these, the aquatic toxicity tests are based on the acute toxicity classification criteria for pesticides to fish in the People's Republic of China National Standard "Specifications for Environmental Safety Assessment of Chemical Pesticides, Part 12: Acute Toxicity Tests to Fish" (GB / T31270.12-2014), and the 96-hour acute toxicity of pentathiocenium zinc to zebrafish was "low toxicity."

[0163] In the "Daphnia acute immobilization test," the 48-hour EC50 of zinc pentathiocenium for Daphnia magna was calculated using DPS statistical analysis software (version 18.10) based on the test solution concentration and the average inhibition rate of Daphnia magna. The 48-hour EC50 for Daphnia magna was 3.20 mg ai / L, with a 95% confidence interval of 2.86 mg ai / L to 3.58 mg ai / L. According to the classification criteria for pesticide toxicity to Daphnia in GB / T31270.13-2014, the 48-hour acute toxicity of TG-025 to Daphnia magna under these test conditions was classified as "poisoning."

[0164] For acute toxicity, acute toxicity reactions and mortality were examined after oral administration to SD rats. In this study, a limit test method was used, and the dose of zinc pentathiocenium was set at 5000 mg / kg body weight. The median lethal dose (LD50) for both male and female SD rats was >5000 mg / kg, and they were classified as "slightly toxic." The acute dermal median lethal dose (LD50) for both male and female SD rats was >2000 mg / kg, and they were classified as "lowly toxic."

[0165] In acute inhalation toxicity tests on rats of zinc pentathiocenium, the oral and nasal exposure concentration range was 5040-5070 mg / m 3 In the aerosol environment of the test product (corresponding to an inhalation dose of the test product of approximately 900 mg / kg), the median lethal concentration (LC50) for male and female SD rats was >5000 mg / m 3 and was classified as "slightly toxic."

[0166] The sensitization rate of pentathiocenium zinc in Hartley guinea pigs was 0%, and according to the pesticide sensitization potency criteria, the sensitization potency classification was "weak." The acute dermal median lethal dose (LD50) in both male and female SD rats was >2000 mg / kg body weight, and it was classified as "low toxicity."

[0167] The highest average score for skin irritation of New Zealand White rabbits for the test product pentathiocenium zinc at 24, 48, and 72 hours of observation was 0, and according to the pesticide skin irritation strength classification standards, the skin irritation strength of pentathiocenium zinc technical grade in New Zealand White rabbits was classified as "non-irritating." The eye irritation strength of the test product pentathiocenium zinc technical grade in New Zealand White rabbits was classified as "mild irritation" (recovered in 24 hours).

[0168] Regarding genotoxicity, in a bacterial reverse mutation test, pentathiocenium zinc technic was not mutagenic in any of the test strains, and the test results were negative. In an in vivo mammalian bone marrow polychromatic erythrocyte micronucleus test in mice, pentathiocenium zinc technic was not mutagenic in mouse polychromatic erythrocytes, and the test results were negative. In an in vitro mammalian cell chromosomal aberration test, pentathiocenium zinc technic was not mutagenic in in vitro cultured CHL mammalian cells, and the test results were negative. In an in vitro mammalian cell gene mutation test, pentathiocenium zinc technic did not induce gene mutations in in vitro cultured mouse lymphoma cell L5178YTK+ / - clone (3.7.2c), and the test results were negative.

[0169] Ecotoxicological and subchronic toxicity tests are currently underway. Based on the above toxicological data, this substance, pentathiocenium zinc, has extremely low toxicity across all exposure routes, the risk of contact is manageable, and it has no significant genotoxicity or sensitizing toxicity, meeting the safety requirements for pesticide management and showing good prospects for industrial application.

[0170] The present invention will be described in more detail below with reference to examples. 5 g (37.54 mmol) of 2-amino-5-thio-1,3,4-pentathiocenium was used as the starting material and heated with stirring in ethanol as the solvent until the starting material was completely dissolved. The mixture was then cooled to 30 °C and a formaldehyde or paraformaldehyde solution was slowly added. The reaction mixture was allowed to react at room temperature (25 ± 5 °C) for 1-2 hours. Dilute hydrochloric acid was added to the reaction mixture, and the precipitated solid was recrystallized. The solid was then vacuum filtered to remove water and dried at 50-70 °C. Finally, recrystallization yielded 8.73 g of 5,11,17-trithia-1,3,7,9,13,15,19,20,21-nonazatricyclo[14.2.1.14,7.110,13]henicosa-4(20),10(21),16(19)-triene-6,12,18-trithione (X5) compound. The melting point was over 250°C, the content was 93-95%, and the yield was 51.40%.

[0171] 0.5 g (1.15 mmol) of the intermediate 5,11,17-trithia-1,3,7,9,13,15,19,20,21-nonazatricyclo[14.2.1.14,7.110,13]henicosa-4(20),10(21),16(19)-triene-6,12,18-trithione (X5) was placed in a 100 mL three-neck flask, water was added as a solvent, and 48.21 mg (1.21 mmol) of NaOH was added as an acid scavenger. Finally, 89.95 mg (0.66 mmol) of ZnCl2 dissolved in water was added to the system, and the reaction was carried out at room temperature for 1 to 2 hours. After the reaction was complete, water was added and the precipitated solid was filtered through a Buchner funnel or a three-neck funnel and dried to give chloro-bis[5,11,17-trithia-1,3,7,9,13,15,19,20,21-nonazatricyclo[14.2.1.14,7.110,13]henicosa-4(20),10(21),16(19)-triene-6,12,18-trithione]zinc (pentathiocenium zinc). The sample mass was 512 mg, the yield was 91.78%, and the melting point was over 250 °C.

[0172] The resulting drug substance is ground with kaolin clay and a surfactant to obtain a 10% suspension, which is then diluted with water to 200-400 μg / mL and sprayed onto the leaves of plants.

[0173] The above is merely a preferred embodiment of the present invention, and does not limit the present invention in any way. Based on the technical idea of ​​the present invention, simple modifications, equivalent replacements and alterations made to the above embodiments are all included in the technical scope of the present invention.

Claims

1. Pentathiocenium zinc, or a stereoisomer thereof, or a salt thereof, or a solvate thereof, The chemical structural formula of the pentathiocenium zinc is represented by the following formula, or a stereoisomer thereof, a salt thereof, or a solvate thereof.

2. Intermediate 5,11,17-trithia-1,3,7,9,13,15,19,20,21-nonazatricyclo[14.2.1.1 ４，７ .1 １０，１３ ] A method for producing pentathiocenium zinc, which comprises reacting henicosa-4(20),10(21),16(19)-triene-6,12,18-trithione (X5) as a raw material to obtain pentathiocenium zinc, and the reaction is represented by the following formula:

3. a step of using 2-amino-5-thio-1,3,4-pentathiocenium as a raw material, adding water as a solvent, adding sodium hydroxide as an acid scavenger, stirring to dissolve, gradually adding a formaldehyde or paraformaldehyde solution, and reacting at room temperature for 1 to 2 hours; The precipitated solid was recrystallized, filtered under vacuum, and the water was removed. The solid was dried at 50 to 70°C to obtain 5,11,17-trithia-1,3,7,9,13,15,19,20,21-nonazatricyclo[14.2.1.1 ４，７ .1 １０，１３ ] a step of obtaining henicosa-4(20),10(21),16(19)-triene-6,12,18-trithione (intermediate X5); adding the intermediate X5 to an aqueous sodium hydroxide solution, completely dissolving the raw materials, adding an aqueous zinc chloride solution, and reacting at room temperature for 1 to 2 hours; filtering the precipitated solid with a Buchner funnel under suction, and drying at 50 to 80°C.

3. The method for producing zinc pentathiocenium according to claim 2.

4. A composition comprising the zinc pentathiocenium of claim 1, or a stereoisomer thereof, or a salt thereof, or a solvate thereof, and an agriculturally usable adjuvant or fungicide, wherein the composition is in the form of a suspension, an emulsion, a dust, a granule, a solution, an ultra-low volume spray, a microcapsule, a fumigation agent, or an emulsion in water.

5. Use of the zinc pentathiocenium, or a stereoisomer thereof, or a salt thereof, or a solvate thereof according to claim 1 in the manufacture of a drug for controlling plant bacterial diseases, The plant bacterial disease is rice bacterial leaf blight, rice bacterial streak, citrus canker, citrus yellow dragon disease, tomato bacterial wilt, tobacco bacterial wilt, peach needle hole, cabbage black rot, Chinese cabbage soft rot, melon bacterial spot, and watermelon bacterial fruit rot.

6. Use of the composition according to claim 4 in the manufacture of a drug for controlling plant bacterial diseases, The plant bacterial disease is rice bacterial leaf blight, rice bacterial streak, citrus canker, citrus yellow dragon disease, tomato bacterial wilt, tobacco bacterial wilt, peach needle hole, cabbage black rot, Chinese cabbage soft rot, melon bacterial spot, and watermelon bacterial fruit rot.

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