Chromone compounds containing 5-sulfone-1,3,4-thiadiazole, and methods of preparation and fungicidal applications thereof

Abstract

The application discloses a 5-sulfone-1,3,4-thiadiazole-containing chromone compound with a structure as shown in formula V, R1 is selected from H, F, Cl, Br and methyl; R2 is selected from H, F, Br and methyl; R3 is selected from H, Cl and Br; R is selected from R4 is selected from C1-C6 linear or branched alkyl, cyclohexyl, allyl and benzyl, R5 is selected from C1-C6 linear or branched alkyl, R6 is selected from C1-C6 linear or branched alkyl, allyl and benzyl. The 5-sulfone-1,3,4-thiadiazole-containing chromone compound has high and / or broad-spectrum fungicidal activity. The application further discloses application of the 5-sulfone-1,3,4-thiadiazole-containing chromone compound in killing crop pathogenic fungi and crop pathogenic bacteria or in preparing a pesticide preparation for preventing and treating crop pathogenic fungi and crop pathogenic bacteria.

Description

Technical Field

[0001] This invention relates to agricultural fungicides, specifically to chromone compounds containing 5-sulfon-1,3,4-thiadiazole, their preparation methods, and their applications in fungicide application. Background Technology

[0002] Chromone derivatives are widely found in the secondary metabolites of plants and microorganisms, and are an important class of natural products. Due to the wide and diverse activities of various substituted chromone derivatives, such as antibacterial, anti-inflammatory, antitumor, antiviral, and antioxidant activities, they have attracted widespread attention from drug developers.

[0003] 1,3,4-Thiadiazoles and sulfones have become a hot topic in fungicide research due to their wide range of activities. However, novel chromone compounds containing 5-sulfone-1,3,4-thiadiazoles, their synthetic routes, and fungicidal activities have not yet been reported. Therefore, the development of sulfone-1,3,4-thiadiazole compounds with natural chromone skeletons is of positive significance and extremely important value.

[0004] Currently, there is no known method to synthesize novel compounds like chromone by directly linking chromone, 1,3,4-thiadiazole, and sulfone fragments. Summary of the Invention

[0005] The purpose of this invention is to provide a series of novel 5-sulfonyl-1,3,4-thiadiazole chromone compounds. By employing a substructure splicing strategy of active units, the sulfonyl group and the 1,3,4-thiadiazole active fragment are spliced ​​onto the chromone. In the study of bioactivity in agricultural applications, these compounds have shown excellent bactericidal effects against pathogenic fungi and bacteria of crops, thus expanding the bactericidal spectrum.

[0006] The objective of this invention is achieved through the following technical solution:

[0007] Compounds containing 5-sulfone-1,3,4-thiadiazole chromones with structures as shown in Formula V:

[0008]

[0009] Wherein, R1 is selected from H, F, Cl, Br, and methyl; R2 is selected from H, F, Br, and methyl; and R3 is selected from H, Cl, and Br.

[0010] R is selected from

[0011] R4 is selected from C1-C6 straight-chain or branched alkyl, cyclohexyl, allyl, and benzyl; R5 is selected from C1-C6 straight-chain or branched alkyl.

[0012] R6 is selected from C1-C6 straight-chain or branched alkyl, allyl, and benzyl groups;

[0013] However, it does not include: R1 selected from H, methyl, R2 selected from H, R3 selected from H, R4 selected from benzyl, R5 selected from methyl; R1 selected from Cl, methyl, R2 selected from H, R3 selected from H, R6 selected from benzyl; R1 selected from H, R2 selected from Br, R3 selected from H, R6 selected from benzyl.

[0014] Preferably, R1 is selected from H, F, Cl, Br, and methyl; R2 is selected from H, F, Br, and methyl; R3 is selected from H, Cl, and Br; R4 is selected from C1-C4 straight-chain or branched alkyl, cyclohexyl, allyl, and benzyl; R5 is selected from C1-C2 alkyl; and R6 is selected from C1-C4 straight-chain or branched alkyl, allyl, and benzyl. However, it does not include: R1 selected from H and methyl, R2 selected from H, R3 selected from H, R4 selected from benzyl, and R5 selected from methyl; R1 selected from Cl and methyl, R2 selected from H, R3 selected from H, and R6 selected from benzyl; R1 selected from H, R2 selected from Br, R3 selected from H, and R6 selected from benzyl.

[0015] More preferably, R1 is selected from H, F, Cl, Br, and methyl; R2 is selected from H, F, Br, and methyl; R3 is selected from H, Cl, and Br; R4 is selected from C1-C4 straight-chain or branched alkyl, cyclohexyl, allyl, and benzyl; R5 is selected from C1-C2 alkyl; and R6 is selected from C1-C4 straight-chain or branched alkyl, allyl, and benzyl. However, it excludes: R1 selected from methyl, R2 selected from H, R3 selected from H, R4 selected from n-propyl, allyl, and benzyl, and R5 selected from methyl; R1 selected from H, and R2 selected from Br. R3 is selected from H, R4 is selected from n-propyl, R5 is selected from methyl; R1 is selected from H, R2 is selected from H, R3 is selected from H, R4 is selected from benzyl, R5 is selected from methyl; R1 is selected from F, R2 is selected from H, R3 is selected from H, R4 is selected from benzyl, R5 is selected from methyl; R1 is selected from methyl, R2 is selected from H, R3 is selected from H, R6 is selected from methyl, allyl, benzyl; R1 is selected from F, C, R2 is selected from H, R3 is selected from H, R6 is selected from benzyl; R1 is selected from H, R2 is selected from H, Br, R3 is selected from H, R6 is selected from benzyl.

[0016] More preferably, R is selected from In this case, R1 is selected from H, R2 is selected from H, R3 is selected from H, R4 is selected from C1-C4 straight-chain alkyl, and R5 is selected from C1-C2 alkyl; R1 is selected from F, R2 is selected from H, R3 is selected from H, R4 is selected from isopropyl, and R5 is selected from ethyl; R1 is selected from Cl, R2 is selected from H, R3 is selected from H, R4 is selected from C1-C4 straight-chain or branched-chain alkyl, and R5 is selected from methyl or ethyl; R1 is selected from Cl, R2 is selected from H, R3 is selected from Cl, R4 is selected from methyl, isopropyl, or cyclohexyl, and R5 is selected from methyl; R1 is selected from Cl, R2 is selected from H, R3 is selected from bromine, R4 is selected from isopropyl, and R5 is selected from methyl; R1 is selected from Br, R2 is selected from H, R3 is selected from Cl, R4 is selected from C1-C4 straight-chain or branched-chain alkyl or cyclohexyl, and R5 is selected from methyl; R1 is selected from Br, R2 is selected from F or Br, R3 is selected from H, R4 is selected from methyl or isopropyl, and R5 is selected from methyl.

[0017] R is selected from When; R1 is selected from H, R2 is selected from H, R3 is selected from H, R6 is selected from ethyl, isopropyl, allyl; R1 is selected from H, R2 is selected from methyl, R3 is selected from H, R6 is selected from ethyl, isopropyl; R1 is selected from methyl, R2 is selected from H, R3 is selected from H, R6 is selected from n-propyl, isopropyl; R1 is selected from H, R2 is selected from Br, R3 is selected from H, R6 is selected from n-propyl, isopropyl, allyl; R1 is selected from H, R2 is selected from F, R3 is selected from H, R6 is selected from methyl, isopropyl R1 is selected from F, R2 from H, R3 from H, and R6 from ethyl, n-propyl, and isopropyl; R1 is selected from Cl and Br, R2 from H, R3 from H, and R6 from methyl, ethyl, n-propyl, isopropyl, and n-butyl; R1 is selected from Cl, R2 from H, R3 from H, and R6 from allyl; R1 is selected from Cl, R2 from H, R3 from Cl, and R6 from n-butyl; R1 is selected from Br, R2 from H, R3 from Br, and R6 from methyl.

[0018] Another object of the present invention is to provide compounds containing 5-sulfone-1,3,4-thiadiazole chromones with the structure shown in Formula I:

[0019]

[0020] R1, R2, R3, R4, and R5 are as described above.

[0021] Another object of the present invention is to provide compounds containing 5-sulfone-1,3,4-thiadiazole chromones with the structure shown in Formula II:

[0022]

[0023] R1, R2, R3, and R6 are as described above.

[0024] Another object of the present invention is to provide a method for preparing the aforementioned 5-sulfone-1,3,4-thiadiazole chromone compound.

[0025] When R is selected The synthesis route is as follows:

[0026]

[0027] Among them, R1, R2, R3, R4, and R are as described above;

[0028] Using 2-hydroxyacetophenone (as shown in III) as a starting material, a cyclization reaction, a condensation reaction, and an oxidation reaction are performed to obtain a 5-sulfone-1,3,4-thiadiazole chromone compound (as shown in Formula I), comprising the following steps:

[0029] Step (1): Under ice bath conditions, POCl3 is slowly added dropwise to dry DMF while stirring. The temperature is maintained at 0-5℃ during the addition. After the addition is complete, the reaction is carried out for 1 hour to obtain VM reagent. o-hydroxyacetophenone of Formula III is added to VM reagent in batches, the temperature is raised to 50℃, the reaction is carried out for 2 hours, and then the temperature is raised to 80℃, the reaction is carried out for 4 hours. The reaction solution is filtered and the filter cake is dried to obtain 3-formylchrome ketone with the structure shown in Formula VI. The molar ratio of 2-hydroxyacetophenone to phosphorus oxychloride is 1:3.

[0030] Step (2): Using anhydrous ethanol as the reaction solvent, 3-formyl chromone of formula VI and dithiocarbamate of formula IVa are reacted under reflux for 4-5 hours. The reaction solution is cooled, and a large amount of solid is precipitated. The solid is filtered and the filter cake is dried. The filter cake is then added to the anhydride of formula VIII and refluxed for 2 hours. The reaction solution is cooled and kept at -20°C overnight, and a large amount of white flocculent solid is precipitated. The solid is filtered and the filter cake is dissolved in dichloromethane. The mixture is stirred in an ice bath, and m-chloroperoxybenzoic acid is added in batches. The reaction is carried out for 12 hours to obtain the target compound shown in formula I. The molar ratio of 3-formyl chromone to dithiocarbamate is 1:1, and the molar ratio of 3-formyl chromone to m-chloroperoxybenzoic acid is 1:1.8.

[0031] When R is selected The synthesis route is as follows:

[0032]

[0033] Among them, R1, R2, R3, and R6 are as described above;

[0034] Includes the following steps:

[0035] Step (1): Under ice bath conditions, POCl3 is slowly added dropwise to dry DMF while stirring. The temperature is maintained at 0-5℃ during the addition. After the addition is complete, the reaction is carried out for 1 hour to obtain VM reagent. o-hydroxyacetophenone of Formula III is added to VM reagent in batches, the temperature is raised to 50℃, the reaction is carried out for 2 hours, and then the temperature is raised to 80℃, the reaction is carried out for 4 hours. The reaction solution is filtered and the filter cake is dried to obtain 3-formylchrome ketone with the structure shown in Formula VI. The molar ratio of 2-hydroxyacetophenone to phosphorus oxychloride is 1:3.

[0036] Step (2): Using anhydrous ethanol as the reaction solvent, 3-formyl chromone (Formula VI) and dithiocarbamate (Formula IVa) are reacted under reflux for 4-5 hours. The reaction solution is cooled, and a large amount of solid precipitates. The solid is filtered and the filter cake is dried. The filter cake is then added to acetic anhydride and refluxed for 2 hours. The reaction solution is cooled and kept at -20°C overnight, and a large amount of white flocculent solid precipitates. The solid is filtered and the filter cake is dissolved in dichloromethane. The mixture is stirred in an ice bath, and m-chloroperoxybenzoic acid is added in batches. The reaction is carried out for 12 hours. The solvent is removed by vacuum distillation of the reaction solution. The obtained solid is dissolved in DMSO and heated to 100°C for 4 hours to obtain the target compound shown in Formula II. The molar ratio of 3-formyl chromone to dithiocarbamate is 1:1, and the molar ratio of 3-formyl chromone to m-chloroperoxybenzoic acid is 1:1.8.

[0037] The preparation method of the 5-sulfone-1,3,4-thiadiazole chromone compound described in this invention also includes the purification of the target compound. There are no special requirements for the purification method. Those skilled in the art can use various conventional purification methods, such as extraction with an extractant, drying with a drying agent, and removing impurities by column chromatography to obtain the high-purity target compound.

[0038] The 5-sulfonyl-1,3,4-thiadiazole chromone compounds described in this invention exhibit highly effective and / or broad-spectrum bactericidal activity. Another object of this invention is to provide the use of the aforementioned 5-sulfonyl-1,3,4-thiadiazole chromone compounds in killing pathogenic fungi and bacteria of crops, or in the preparation of pesticide formulations for controlling pathogenic fungi and bacteria of crops.

[0039] The pathogenic fungi of crops mentioned are *Rhizoctonia solani* (rice sheath blight), *Botrytis cinerea* (strawberry gray mold), *Gibberella zeae* (wheat scab), *Altemaria solani* (tomato early blight), *Colletotrichum orbiculare* (cucumber anthracnose), and *Alternaria alternata* (apple spot), with *Rhizoctonia solani*, *Altemaria solani*, and *Colletotrichum orbiculare* (cucumber anthracnose) being the most preferred.

[0040] The pathogenic bacteria of crops mentioned are *Xanthomonas oryzae pv oryzae*, *Ralstonia solanacearum*, and *Xanthomonas axonopodis pvcitri*, with *Xanthomonas oryzae pv oryzae* and *Xanthomonas axonopodis pvcitri* being preferred.

[0041] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0042] This invention uses various substituted or unsubstituted 2-hydroxyacetophenones, various substituted or unsubstituted acid anhydrides, and dithiocarbamates as starting materials to obtain 5-sulfone-1,3,4-thiadiazole chromone compounds through a simple one-step reaction. The preparation method of these 5-sulfone-1,3,4-thiadiazole chromone compounds is simple to operate, involves no precious metals in the reaction, is highly efficient, and yields a high amount of product.

[0043] The 5-sulfonyl-1,3,4-thiadiazole chromone compounds of this invention have good fungicidal activity. These compounds exhibit highly efficient and / or broad-spectrum fungicidal activity and can be used to treat crop diseases caused by fungi and bacteria. Detailed Implementation

[0044] The technical solution of the present invention will be described in detail through embodiments. In the embodiments, unless otherwise specified, all raw materials used are commercially available (Table 1), and their purity level is analytical grade, with no signs of expiration, moisture absorption, or deterioration. The room temperature is 25°C.

[0045] Table 1. List of Main Reagents

[0046]

[0047] Me represents methyl, Et represents ethyl, n-Pr represents n-propyl, i-Pr represents isopropyl, n-Bu represents n-butyl, t-Bu represents tert-butyl, allyl represents allyl, Bn represents benzyl, and Cy represents cyclohexyl.

[0048] Example 1

[0049] The synthetic route for synthesizing the 5-sulfone-1,3,4-thiadiazole chromone compound of formula I, using 2-hydroxyacetophenone (formula III) and dithiocarbamate (formula IVa) as starting materials, is as follows:

[0050]

[0051] Among them, R1, R2, R3, R4, and R5 are shown in Table 2, and X is selected from Br.

[0052] The specific steps are as follows:

[0053] Cyclization reaction: In a 100 mL round-bottom flask, add 30 mL of dry DMF. Under ice bath conditions, slowly add 60 mmol of POCl3 dropwise to the dry DMF while stirring. Maintain the temperature at 0-5 °C during the addition. After the addition is complete, react for 1 h to obtain the VM reagent. Subsequently, add 20 mmol of o-hydroxyacetophenone (Formula III) to the VM reagent in portions, raise the temperature to 50 °C, react for 2 h, then raise the temperature to 80 °C, and react for 4 h. Filter the reaction solution, dry the filter cake, and obtain 3-formylchromone (Formula VI).

[0054] Preparation of dithiocarbamate (Formula IVa): Potassium hydroxide (0.15 mol) was dissolved in a mixed solvent of 10 mL isopropanol and 12 mL water. 80% hydrazine hydrate (0.15 mol) was added, and carbon disulfide (0.15 mol) was slowly added dropwise under ice bath conditions. The mixture was stirred for 2 h. Subsequently, bromoalkane (R4X, 0.18 mol) was added, and the mixture was stirred for 4–8 h. After the reaction was complete, an appropriate amount of water was added to the reaction solution, and the mixture was extracted five times with 50 mL of dichloromethane. The organic phases were combined, dried over anhydrous sodium sulfate, and the dichloromethane was evaporated under reduced pressure to obtain dithiocarbamate as shown in Formula IVa.

[0055] Condensation and oxidation reaction: 2.5 mmol of 3-formylchrome ketone (Formula VI) was dissolved in 30 mL of anhydrous ethanol, and 2.5 mmol of dithiocarbamate (Formula IVa) was added. The mixture was heated to reflux for 4-5 h. After cooling, a large amount of solid precipitated. The solid was filtered and the filter cake was dried. The dried filter cake was added to 5 mL of acid anhydride (Formula VIII), and the mixture was refluxed for 2 h. After cooling, the mixture was placed in a -20°C refrigerator overnight, and a large amount of white flocculent solid precipitated. The solid was filtered, and the resulting filter cake was dissolved in 20 mL of dichloromethane. The mixture was stirred in an ice bath, and 4.5 mmol of 75% m-chloroperoxybenzoic acid was added in portions. The reaction was carried out for 12 h, and the reaction progress was monitored by TLC. After the reaction was completed, the solid was obtained by vacuum distillation. The solid was then reacted with a mixture of dichloromethane and ethanol (V... 乙醇 :V 二氯甲烷 The mixture of 4:1 was recrystallized at 0°C to obtain the target compound shown in Formula I.

[0056] The compounds containing 5-sulfone-1,3,4-thiadiazole chromones, represented by Formula I, are shown in Table 2.

[0057] Table 2. Compounds containing 5-sulfone-1,3,4-thiadiazole chromones

[0058]

[0059] Compound 1: 3-(3-acetyl-5-(methanesulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-chromone: white solid, yield: 73.5%, mp 206.6-207.2; 1 H NMR (400MHz, CDCl3) δ8.39 (s, 1H), 8.13 (d, J = 6.6Hz, 1H), 7.77 (t, J = 7.0Hz, 1H), 7. 56(d,J=8.4Hz,1H),7.48(t,J=7.6Hz,1H),6.09(s,1H),3.50(s,3H),2.49(s,3H); 13 C NMR (100MHz, CDCl3) δ175.48,170.23,157.75,156.29,135.22,126.45,126.01,122.65,118.50,85.78,45.25,22.30; HR-MS(ESI)m / zCalcd.For C 14 H 13 N₂O₆S₂([M+H)) + ):369.0210,Found:369.0215.

[0060] Compound 2: 3-(3-acetyl-5-(methanesulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-6-bromo-chromone: yellow solid, yield: 59.8%, mp 216.1-216.7; 1 H NMR (400MHz, CDCl3) δ8.39(s,1H),8.26(d,J=2.4Hz,1H),7.85(dd,J=8.9,2.4Hz,1H),7.46(d,J=9.0Hz,1H),6.07(s,1H),3.49(s,3H),2.49(s,3H). 13 C NMR (100MHz, CDCl3) δ174.34,170.24,157.88,155.01,152.94,138.22,128.62, 123.92,120.36,120.07,118.39,85.52,45.23,22.26.HR-MS(ESI)m / zCalcd.For C 14 H 12 BrN2O6S2([M+H] + ):446.9315,Found:446.9314.

[0061] Compound 3: 3-(3-acetyl-5-(methanesulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-6-fluoro-chromone: white solid, yield: 78.2%, mp 215.7-216.2; 1 H NMR (400MHz, CDCl3) δ8.40(s,1H),7.76(dd,J=7.8,3.0Hz,1H),7.59(dd,J=9.2,4.1Hz,1H),7.53-7.46(m,1H),6.09(s,1H),3.49(s,3H),2.49(s,3H). 13 C NMR (100MHz, DMSO) δ175.07, 170.27, 159.81 (d, J = 245.6Hz), 159.66, 154.49, 152.75, 124.06 (d, J = 9.1Hz), 12 3.90(d,J=14.0Hz),122.08(d,J=8.0Hz),116.88,110.36(d,J=20.5Hz),84.85,45.65,22.59.HR-MS(ESI)m / z Calcd.ForC 14 H 12 FN2O6S2([M+H) + ):387.0115,Found:387.0124.

[0062] Compound 4: 3-(3-acetyl-5-(methanesulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-6-chloro-chromone: yellow solid, yield: 65.7%, mp 208.8-210.4; 1 H NMR (400MHz, CDCl3) δ8.39(s,1H),8.09(d,J=2.5Hz,1H),7.71(dd,J=9.0,2.5Hz,1H),7.53(d,J=9.0Hz,1H),6.08(s,1H),3.49(s,3H),2.49(s,3H). 13 C NMR(100MHz,DMSO)δ174.64,170.21,159.63,154.74,154.44,135.60,131.27,1 24.60,123.85,121.61,117.46,84.73,45.62,22.62.HR-MS(ESI)m / zCalcd.For C 14 H 12 ClN2O6S2([M+H) + ):402.9820,Found:402.9835.

[0063] Compound 5: 3-(3-acetyl-5-(methanesulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-6-methyl-chromone: yellow solid, yield: 82.1%, mp 198.2-199.1; 1 H NMR (400MHz, CDCl3) δ8.37(s,1H),7.90(s,1H),7.57(dd,J=8.6,2.1Hz,1H),7.45(d,J=8.6Hz,1H),3.50(s,3H),2.48(s,3H),2.45(s,3H). 13 CNMR (100MHz, CDCl3) δ175.52,170.20,157.74,154.88,154.60,136.68,136.44,125 .18,122.30,118.22,118.02,85.78,45.19,22.30,20.98.HR-MS(ESI)m / zCalcd.For C 15 H 15 N₂O₆S₂([M+H)) + ):383.0366,Found:383.0374.

[0064] Compound 6: 3-(3-acetyl-5-(methanesulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-7-bromo-chromone: yellow solid, yield: 61.7%, mp 223.1-224.8; 1 H NMR (400MHz, CDCl3) δ8.37(s,1H),8.01(d,J=8.6Hz,1H),7.78(s,1H),7.62(d,J=8.5Hz,1H),6.08(s,1H),3.50(s,3H),2.51(s,3H). 13 C NMR (100MHz, CDCl3) δ174.86,170.22,157.69,156.18,154.99,130.17,129.80,127.31,121.62,118.56,100.00,85.52,45.28,22.29.HR-MS(ESI)m / z Calcd.ForC 14 H 12 BrN2O6S2([M+H] + ):446.9315,Found:446.9344.

[0065] Compound 7: 3-(3-acetyl-5-(ethylsulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-chromone: yellow solid, yield: 55.2%, mp 194.3-194.6; 1 H NMR (400MHz, CDCl3) δ8.39(s,1H),8.15(d,J=7.1Hz,1H),7.78(t,J=7.2Hz,1H),7.57(d,J=8.5Hz,1H) ,7.49(t,J=7.5Hz,1H),6.09(s,1H),3.60(dt,J=14.6,7.2Hz,2H),2.50(s,3H),1.60(t,J=7.4Hz,3H). 13 C NMR (100MHz, CDCl3) δ175.46,170.21,157.77,156.27,153.95,135.16,126.3 8,126.00,122.67,118.49,118.08,85.64,51.82,22.31,6.78.HR-MS(ESI)m / z Calcd.ForC 15 H 15 N₂O₆S₂([M+H)) + ):383.0366,Found:383.0384.

[0066] Compound 8: 3-(3-acetyl-5-(ethylsulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-6-bromo-chromone: yellow solid, yield: 67.9%, mp 200.1-201.0; 1 H NMR (400MHz, CDCl3) δ8.37 (s, 1H), 8.26 (d, J = 2.4Hz, 1H), 7.84 (dd, J = 8.9, 2.4Hz, 1H), 7.4 5(d,J=8.9Hz,1H),6.05(s,1H),3.57(q,J=7.4Hz,2H),2.48(s,3H),1.59(t,J=7.4Hz,5H). 13 C NMR (100MHz, CDCl3) δ174.32,170.22,157.90,155.02,153.98,138.15,128.6 0,123.96,120.39,119.98,118.25,85.40,51.81,22.30,6.79.HR-MS(ESI)m / z Calcd.For C 15 H 14 BrN2O6S2([M+H] +):460.9471,Found:460.9487.

[0067] Compound 9: 3-(3-acetyl-5-(ethylsulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-6-fluoro-chromone: yellow solid, yield: 77.8%, mp 197.6-197.8; 1 H NMR (400MHz, CDCl3) δ8.40(s,1H),7.78(dd,J=7.8,3.0Hz,1H),7.60(dd,J=9.2,4.1Hz,1H),7. 54-7.46(m,1H),6.10(s,1H),3.59(dt,J=13.5,7.2Hz,2H),2.50(s,3H),1.60(t,J=7.4Hz,3H). 13 C NMR (100MHz, CDCl3) δ174.85, 170.22, 160.00 (d, J = 249.8Hz), 157.86, 153.97, 152.55, 123.93 (d, J = 7.8Hz), 123. 53(d,J=25.4Hz),120.79(d,J=8.3Hz),117.49,110.95(d,J=24.0Hz),85.45,51.83,22.30,6.78.HR-MS(ESI)m / z Calcd.For C 15 H 14 FN2O6S2([M+H) + ):401.0272,Found:401.0287.

[0068] Compound 10: 3-(3-acetyl-5-(ethylsulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-6-chloro-chromone: yellow solid, yield: 78.4%, mp 201.4-201.9; 1 H NMR (400MHz, CDCl3) δ8.39 (s, 1H), 8.11 (d, J = 2.5Hz, 1H), 7.72 (dd, J = 9.0, 2.6Hz, 1H), 7. 54(d,J=9.0Hz,1H),6.08(s,1H),3.65-3.54(m,2H),2.50(s,3H),1.59(d,J=7.4Hz,3H). 13C NMR (100MHz, CDCl3) δ174.47,170.22,157.92,154.58,153.96,135.39,132.5 2,125.37,123.62,120.23,118.14,85.39,51.81,22.30,6.79.HR-MS(ESI)m / z Calcd.For C 15 H 14 ClN2O6S2([M+H) + ):416.9976,Found:416.9988.

[0069] Compound 11: 3-(3-acetyl-5-(ethylsulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-6-methyl-chromone: white solid, yield: 60.4%, mp 189.7-190.4; 1 H NMR (400MHz, CDCl3) δ8.35(s,1H),7.91(s,1H),7.57(dd,J=8.6,2.0Hz,1H),7.44(d,J=8.6Hz,1 H), 6.06 (s, 1H), 3.59 (dt, J = 14.4, 7.2Hz, 2H), 2.48 (s, 3H), 2.45 (s, 3H), 1.59 (t, J = 7.4Hz, 3H). 13 C NMR (100MHz, CDCl3) δ175.49,170.20,157.61,154.61,153.93,136.65,136.40,1 25.22,122.33,118.20,117.88,85.72,51.80,22.30,20.98,6.77.HR-MS(ESI)m / z Calcd.For C 16 H 17 N₂O₆S₂([M+H)) + ):397.0523,Found:397.0540.

[0070] Compound 12: 3-(3-acetyl-1-oxo-5-(propylsulfonyl)-2,3-dihydro-1,3,4-thiadiazole)-chromone: white solid, yield: 70.5%, mp 189.3-189.8; 1H NMR (400MHz, CDCl3) δ8.37(s,1H),8.13(d,J=6.6Hz,1H),7.77(t,J=7.0Hz,1H),7.55(d,J=8.5Hz,1H),7.47(t, J=7.2Hz,1H),6.07(s,1H),3.61-3.45(m,2H),2.49(s,3H),2.07(td,J=8.7,1.4Hz,2H),1.17(t,J=7.4Hz,3H). 13 C NMR (100MHz, CDCl3) δ175.46,170.23,157.67,156.28,154.31,135.18,126.42,126.01 ,122.67,118.48,118.12,85.68,58.84,22.33,15.96,13.01.HR-MS(ESI)m / zCalcd.For C 16 H 17 N₂O₆S₂([M+H)) + ):397.0523,Found:397.0540.

[0071] Compound 13: 3-(3-acetyl-1-oxo-5-(propylsulfonyl)-2,3-dihydro-1,3,4-thiadiazole)-6-bromochromene: white solid, yield: 68.4%, mp 189.5-189.7; 1 H NMR (400MHz, CDCl3) δ8.37(s,1H),8.25(d,J=2.4Hz,1H),7.85(dd,J=8.9,2.4Hz,1H),7.44(t,J=10.5Hz,1H),6 .05(s,1H),3.52(ddd,J=8.2,6.7,4.6Hz,2H),2.49(s,3H),2.07(dd,J=15.0,7.5Hz,2H),1.18(t,J=7.4Hz,3H). 13 C NMR (100MHz, CDCl3) δ174.34,170.24,157.95,155.01,154.30,138.15,128.59,12 3.95,120.41,119.99,118.23,85.38,58.79,22.32,15.92,13.04.HR-MS(ESI)m / z Calcd.For C 16 H 16 BrN2O6S2([M+H] + ):474.9628,Found:474.9643.

[0072] Compound 14: 3-(3-acetyl-1-oxo-5-(propylsulfonyl)-2,3-dihydro-1,3,4-thiadiazole)-6-fluoro-chromone: white solid, yield: 75.3%, mp 190.1-191.9; 1 H NMR (400MHz, CDCl3) δ8.38(s,1H),7.75(dd,J=7.8,3.0Hz,1H),7.58(dd,J=9.2,4.1Hz,1H),7.52-7.45(m,1H ),6.07(s,1H),3.52(dt,J=8.3,6.5Hz,2H),2.49(s,3H),2.07(dd,J=14.6,7.3Hz,2H),1.17(t,J=7.4Hz,3H). 13 C NMR (100MHz, CDCl3) δ174.88 (d, J = 2.4Hz), 170.22, 159.96 (d, J = 249.5Hz), 158.03, 154.19, 152.55, 123.91 (d, J = 7.8Hz), 123.51 (d,J=25.5Hz),120.84(d,J=8.2Hz),117.48,110.84(d,J=24.0Hz),85.40,58.77,22.31,15.94,13.00.HR-MS(ESI)m / zCalcd.For C 16 H 16 FN2O6S2([M+H) + ):415.0428,Found:415.0447.

[0073] Compound 15: 3-(3-acetyl-1-oxo-5-(propylsulfonyl)-2,3-dihydro-1,3,4-thiadiazole)-6-chloro-chromone: white solid, yield: 72.9%, mp 190.1-190.3; 1 H NMR (400MHz, CDCl3) δ8.38(s,1H),8.08(d,J=2.4Hz,1H),7.71(dd,J=9.0,2.4Hz,1H),7.53(d,J=9.0Hz ,1H),6.07(s,1H),3.57-3.42(m,2H),2.49(s,3H),2.07(dd,J=15.2,7.6Hz,2H),1.18(t,J=7.4Hz,3H). 13C NMR (100MHz, CDCl3) δ174.49,170.22,157.99,154.58,154.25,135.38,132.47,12 5.32,123.62,120.26,118.12,85.36,58.78,22.31,15.93,13.03.HR-MS(ESI)m / z Calcd.ForC 16 H 16 ClN2O6S2([M+H) + ):431.0133,Found:431.0142.

[0074] Compound 16: 3-(3-acetyl-1-oxo-5-(propylsulfonyl)-2,3-dihydro-1,3,4-thiadiazole)-6-methyl-chromone: white solid, yield: 84.3%, mp 153.1-153.6; 1 H NMR (400MHz, CDCl3) δ8.34(s,1H),7.90(s,1H),7.57(d,J=8.5Hz,1H),7.44(d,J=8.6Hz,1H),6.06(s,1H),3 .54(dd,J=15.2,7.2Hz,2H),2.48(s,3H),2.45(s,3H),2.07(dt,J=15.0,7.5Hz,2H),1.18(t,J=7.4Hz,3H). 13 C NMR (100MHz, CDCl3) δ175.49,170.20,157.58,154.60,154.29,136.64,136.41,125.2 0,122.33,118.21,117.88,85.72,58.79,22.32,21.01,15.92,13.02.HR-MS(ESI)m / z Calcd.For C 17 H 19 N₂O₆S₂([M+H)) + ):411.0679,Found:411.0718.

[0075] Compound 17: 3-(3-acetyl-1-oxo-5-(propylsulfonyl)-2,3-dihydro-1,3,4-thiadiazole)-7-bromochromene: white solid, yield: 68.2%, mp 215.8-217.0; 1H NMR (400MHz, CDCl3) δ8.35(s,1H),8.00(d,J=8.6Hz,1H),7.77(d,J=1.7Hz,1H),7.61(dd,J=8.6,1.7Hz,1H),6. 07(s,1H),3.53(ddd,J=8.3,6.8,5.5Hz,2H),2.50(s,3H),2.08(dd,J=15.0,7.5Hz,2H),1.18(t,J=7.4Hz,3H). 13 C NMR (100MHz, CDCl3) δ174.85,170.22,157.70,156.18,154.32,130.10,129.69,12 7.32,121.60,121.56,118.43,85.38,58.84,22.32,15.93,13.00.HR-MS(ESI)m / z Calcd.For C 16 H 16 BrN2O6S2([M+H] + ):474.9628,Found:474.9638.

[0076] Compound 18: 3-(3-acetyl-5-(isopropylsulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-chromone: white solid, yield: 67.1%, mp 211.4-211.7; 1 H NMR (400MHz, CDCl3) δ8.36(s,1H),8.17(d,J=6.5Hz,1H),7.78(t,J=7.0Hz,1H),7.57(d,J=8.5Hz,1H),7.49(t,J= 7.1Hz,1H),6.07(s,1H),3.69(dt,J=13.7,6.9Hz,1H),2.50(s,3H),1.62(d,J=1.7Hz,3H),1.60(d,J=2.4Hz,3H). 13 C NMR (100MHz, CDCl3) δ175.38,170.21,157.60,156.28,153.33,135.12,126.36,12 6.07,122.71,118.45,117.93,85.66,57.39,22.32,15.23,14.96.HR-MS(ESI)m / z Calcd.For C 16 H 17 N₂O₆S₂([M+H)) + ):397.0523,Found:397.0555.

[0077] Compound 19: 3-(3-acetyl-5-(isopropylsulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-6-bromo-chromone: white solid, yield: 66.7%, mp 197.4-197.6; 1 H NMR (400MHz, CDCl3) δ8.35(s,1H),8.28(d,J=2.4Hz,1H),7.84(dd,J=8.9,2.4Hz,1H),7.45(d,J=8.9Hz,1 H),6.03(s,1H),3.66(dt,J=13.8,6.9Hz,1H),2.48(s,3H),1.60(d,J=1.7Hz,3H),1.58(d,J=1.0Hz,3H). 13 C NMR (100MHz, CDCl3) δ174.24,170.22,157.75,155.02,153.35,138.11,128.66,123.99 ,120.36,119.97,118.12,85.42,57.41,22.30,15.25,14.94.HR-MS(ESI)m / zCalcd.For C 16 H 16 BrN2O6S2([M+H] + ):474.9628,Found:474.9664.

[0078] Compound 20: 3-(3-acetyl-5-(isopropylsulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-6-fluoro-chromone: white solid, yield: 74.2%, mp 199.1-199.7; 1 H NMR (400MHz, CDCl3) δ8.36(s,1H),7.78(dd,J=7.9,3.0Hz,1H),7.58(dd,J=9.2,4.1Hz,1H),7.53- 7.45(m,1H),6.06(s,1H),3.66(dt,J=13.7,6.9Hz,1H),2.48(s,3H),1.60(dd,J=8.9,6.9Hz,6H). 13C NMR (100MHz, CDCl3) δ174.79 (s), 170.22 (s), 159.98 (d, J = 249.5Hz), 157.80 (s), 152.92 (d, J = 73.9Hz), 123.96 (d, J = 7.9Hz), 123.60 (s), 123.35(s),120.77(d,J=8.2Hz),117.34(s),110.97(d,J=24.0Hz),85.44(s),57.40(s),22.30(s),15.22(s),14.93(s).HR-MS(ESI)m / z Calcd.For C 16 H 16 FN2O6S2([M+H) + ):415.0428,Found:415.0445.

[0079] Compound 21: 3-(3-acetyl-5-(isopropylsulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-6-chloro-chromone: white solid, yield: 75.2%, mp 198.5-199.6; 1 H NMR (400MHz, CDCl3) δ8.35(s,1H),8.11(d,J=2.5Hz,1H),7.70(dd,J=9.0,2.6Hz,1H),7.52(d,J= 9.0Hz,1H),6.04(s,1H),3.66(dt,J=13.7,6.9Hz,1H),2.48(s,3H),1.60(dd,J=8.8,6.9Hz,6H). 13 C NMR (100MHz, CDCl3) δ174.39,170.23,157.77,154.58,153.33,135.35,132.49,12 5.43,123.65,120.20,118.00,85.41,57.41,22.30,15.24,14.94.HR-MS(ESI)m / z Calcd.For C 16 H 16 ClN2O6S2([M+H) + ):431.0133,Found:431.0172.

[0080] Compound 22: 3-(3-acetyl-5-(isopropylsulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-7-bromo-chromone: white solid, yield: 66.3%, mp 206.4-207.0; 1H NMR (400MHz, CDCl3) δ8.32(s,1H),8.01(d,J=8.6Hz,1H),7.74(d,J=1.7Hz,1H),7.58(dd,J=8.6, 1.7Hz,1H),6.04(s,1H),3.65(dt,J=13.8,6.9Hz,1H),2.48(s,3H),1.59(dd,J=7.8,7.1Hz,6H). 13 C NMR (100MHz, CDCl3) δ174.76,170.20,157.51,156.19,153.45,130.08,129.6 6,127.41,121.57,118.28,85.37,57.42,22.30,15.19,15.00.HR-MS(ESI)m / z Calcd.For C 16 H 16 BrN2O6S2([M+H] + ):474.9628,Found:474.9612.

[0081] Compound 23: 3-(3-acetyl-5-(allylsulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-6-fluoro-chromone: yellow solid, yield: 54.5%, mp 170.1-170.3; 1 H NMR (400MHz, CDCl3) δ8.38(s,1H),7.77(dd,J=7.8,3.0Hz,1H),7.58(dd,J=9.2,4.1Hz,1H),7.54-7.46(m, 1H),6.08(s,1H),6.05-5.93(m,1H),5.65-5.54(m,2H),4.28(ddd,J=31.5,14.2,7.4Hz,2H),2.48(s,3H). 13 CNMR (100MHz, CDCl3) δ174.87 (s), 170.24 (s), 159.96 (d, J = 249.5Hz), 158.16 (s), 153.02 (d, J = 96.4Hz), 126.68 (s), 123.89 (d, J = 7.8Hz), 123.65(s),123.40(s),122.79(s),120.88(d,J=8.2Hz),117.40(s),110.79(d,J=24.0Hz),85.40(s),61.64(s),22.27(s).HR-MS(ESI)m / z Calcd.For C 16 H 14FN2O6S2([M+H) + ):413.0272,Found:413.0280.

[0082] Compound 24: 3-(3-acetyl-5-(allylsulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-6-methyl-chromone: yellow solid, yield: 51.7%, mp 170.3-171.4; 1 H NMR (400MHz, CDCl3) δ8.35(s,1H),7.93(s,1H),7.59(dd,J=8.6,2.1Hz,1H),7.46(d,J=8.6Hz,1H),6.07(s ,1H),6.06-5.94(m,1H),5.69-5.54(m,2H),4.31(ddd,J=32.6,14.2,7.3Hz,2H),2.49(s,3H),2.47(s,3H). 13 C NMR (100MHz, CDCl3) δ175.45,170.22,157.56,154.61,153.67,136.71,136.44,126.65 ,125.21,122.85,122.33,118.21,117.84,85.77,61.70,22.29,21.00.HR-MS(ESI)m / z Calcd.For C 17 H 17 N₂O₆S₂([M+H)) + ):409.0523,Found:409.0513.

[0083] Compound 25: 3-(3-acetyl-5-(phenylsulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-chromone: white solid, yield: 78.2%, mp 205.9-207.0; 1 H NMR (400MHz, CDCl3) δ8.33(s,1H),8.18(dd,J=8.0,1.5Hz,1H),7.79(ddd,J=8.7,7.2,1.6Hz,1H),7.57(d,J=9.2Hz,2H),7 .54(d,J=3.6Hz,1H),7.50(t,J=7.6Hz,1H),7.43(dd,J=5.0,1.7Hz,3H),6.09(s,1H),4.79(q,J=13.9Hz,2H),2.25(s,3H). 13C NMR (100MHz, CDCl3) δ175.44,170.25,157.58,156.28,153.19,135.19,131.66,129.39,128 .88,126.45,126.35,125.98,122.69,118.50,117.75,85.49,64.11,22.08.HR-MS(ESI)m / z Calcd.For C 20 H 17 N₂O₆S₂([M+H)) + ):445.0523,Found:445.0532.

[0084] Compound 26: 3-(3-acetyl-5-(phenylsulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-6-bromo-chromone: white solid, yield: 70.4%, mp 181.8-182.8; 1 H NMR (400MHz, CDCl3) δ8.33(s,1H),8.30(d,J=2.4Hz,1H),7.86(dd,J=8.9,2.4Hz,1H),7.54( dd,J=6.6,2.8Hz,2H),7.50-7.39(m,4H),6.09(s,1H),4.78(q,J=13.9Hz,2H),2.25(s,3H). 13 C NMR (100MHz, CDCl3) δ174.30,170.25,157.72,155.02,153.22,138.15,131.65,129.44,128 .90,128.57,126.23,123.97,120.41,120.00,117.91,85.22,64.12,22.07.HR-MS(ESI)m / z Calcd.ForC 20 H 16 BrN2O6S2([M+H] + ):522.9628,Found:522.9666.

[0085] Compound 27: 3-(3-acetyl-5-(phenylsulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-6-fluoro-chromone: white solid, yield: 77.9%, mp 196.2-197.1; 1H NMR (400MHz, CDCl3) δ8.32(s,1H),7.79(dd,J=7.8,3.0Hz,1H),7.57(dd,J=9.2,4.1Hz,1H),7.50( ddd,J=12.2,7.9,2.5Hz,3H),7.44-7.38(m,3H),6.08(s,1H),4.76(q,J=13.9Hz,2H),2.23(s,3H). 13 C NMR (100MHz, CDCl3) δ174.82, 170.25, 160.00 (d, J = 249.6Hz), 157.74, 153.17, 152.54, 131.64, 129.42, 128.89, 126.26, 123.9 4(d,J=7.9Hz),123.54(d,J=25.5Hz),120.83(d,J=8.2Hz),117.13,110.89(d,J=24.0Hz),85.26,64.12,22.06.HR-MS(ESI)m / z Calcd.ForC 20 H 16 FN2O6S2([M+H) + ):463.0428,Found:463.0472.

[0086] Compound 28: 3-(3-acetyl-5-(phenylsulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-6-chloro-chromone: white solid, yield: 73.7%, mp 193.2-193.8; 1 H NMR (400MHz, CDCl3) δ8.33 (s, 1H), 8.14 (d, J = 2.5Hz, 1H), 7.72 (dd, J = 9.0, 2.6Hz, 1H), 7 .57-7.51(m,3H),7.47-7.40(m,3H),6.09(s,1H),4.78(q,J=13.9Hz,2H),2.25(s,3H). 13 C NMR (100MHz, CDCl3) δ174.43,170.25,157.66,154.58,153.23,135.41,132.57,131.65,129 .44,128.90,126.24,125.37,123.64,120.23,117.81,85.24,64.15,22.06.HR-MS(ESI)m / z Calcd.For C 20 H 16 ClN2O6S2([M+H) +):479.0133,Found:479.0171.

[0087] Compound 29: 3-(3-acetyl-5-(phenylsulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-6-methyl-chromone: white solid, yield: 77.8%, mp 178.9-179.8; 1 H NMR (400MHz, CDCl3) δ8.28(s,1H),7.93(d,J=1.0Hz,1H),7.55(ddd,J=9.5,8.0,2.8Hz, 3H),7.47-7.37(m,4H),6.06(s,1H),4.77(q,J=13.9Hz,2H),2.45(s,3H),2.23(s,3H). 13 C NMR (100MHz, CDCl3) δ175.47,170.23,157.48,154.61,153.23,136.69,136.43,131.68,129.37 ,128.87,126.37,125.19,122.35,118.22,117.56,85.55,64.07,22.09,21.01.HR-MS(ESI)m / z Calcd.ForC 21 H 19 N₂O₆S₂([M+H)) + ):459.0679,Found:459.0674.

[0088] Compound 30: 3-(3-acetyl-5-(phenylsulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-7-bromo-chromone: white solid, yield: 69.8%, mp 263.1-263.2; 1 H NMR (400MHz, CDCl3) δ8.29(s,1H),8.03(d,J=8.6Hz,1H),7.77(d,J=1.6Hz,1H),7.61(dd,J=8.6,1.6Hz,1H) ,7.54(dd,J=6.6,2.8Hz,2H),7.43(dd,J=5.0,1.6Hz,3H),6.08(s,1H),4.77(q,J=13.9Hz,2H),2.25(s,3H). 13C NMR (100MHz, CDCl3) δ174.80,170.25,157.47,156.18,153.18,131.63,130.14,129.70 ,129.43,128.90,127.34,126.27,121.59,118.08,85.23,64.20,22.06.HR-MS(ESI)m / z Calcd.For C 20 H 16 BrN2O6S2([M+H] + ):522.9628,Found:522.9630.

[0089] Compound 31: 6-Fluoro-3-(5-(methanesulfonyl)-1-oxo-3-propionyl-2,3-dihydro-1,3,4-thiadiazole)-chromone: yellow solid, yield: 54.2%, mp 177.0-177.7; 1 H NMR(400MHz, CDCl3)δ8.39(s,1H),7.76(dd,J=7.8,3.0Hz,1H),7.58(dd,J=9.2,4.1Hz,1H), 7.53-7.45(m,1H),6.09(s,1H),3.48(s,3H),2.88(q,J=14.8Hz,2H),1.16(t,J=7.4Hz,3H). 13 C NMR (100MHz, CDCl3) δ174.91, 173.77, 159.99 (d, J = 249.6Hz), 158.07, 154.60, 152.56, 123.90 (d, J = 7.9Hz), 123. 54(d,J=25.5Hz),120.85(d,J=8.2Hz),117.69,110.87(d,J=24.0Hz),85.69,45.20,27.95,8.14.HR-MS(ESI)m / z Calcd.For C 15 H 14 FN2O6S2([M+H) + ):401.0272,Found:401.0276.

[0090] Compound 32: 6-chloro-3-(5-(methanesulfonyl)-1-oxo-3-propionyl-2,3-dihydro-1,3,4-thiadiazole)-chromone: white solid, yield: 77.2%, mp 182.2-182.8; 1H NMR (400MHz, CDCl3) δ8.41 (s, 1H), 8.11 (d, J = 2.5Hz, 1H), 7.73 (dd, J = 9.0, 2.6Hz, 1H), 7.54 (d,J=9.0Hz,1H),6.10(s,1H),3.50(s,3H),2.89(q,J=14.8Hz,2H),1.18(t,J=7.4Hz,3H). 13 C NMR (100MHz, CDCl3) δ174.51,173.77,158.04,154.64,154.58,135.40,132.5 1,125.33,123.59,120.27,118.35,85.65,45.20,27.96,8.14.HR-MS(ESI)m / z Calcd.For C 15 H 14 ClN2O6S2([M+H) + ):416.9976,Found:416.9999.

[0091] Compound 33: 3-(5-(isopropylsulfonyl)-1-oxo-3-propionyl-2,3-dihydro-1,3,4-thiadiazole)-chromone: white solid, yield: 68.1%, mp 185.3-186.3; 1 H NMR (400MHz, CDCl3) δ8.37(s,1H),8.17(dd,J=8.0,1.4Hz,1H),7.82-7.74(m,1H),7.57(d,J=8.4Hz,1H),7.49(t,J=7 .5Hz,1H),6.07(s,1H),3.69(dt,J=13.8,6.9Hz,1H),2.94-2.83(m,2H),1.63(d,J=7.8Hz,6H),1.18(t,J=7.4Hz,3H). 13 C NMR (100MHz, CDCl3) δ175.38,173.72,157.68,156.28,153.00,135.10,126.32,126. 01,122.72,118.47,117.98,85.83,57.37,27.99,15.23,14.94,8.20.HR-MS(ESI)m / z Calcd.For C 17 H 19 N₂O₆S₂([M+H)) + ):411.0679,Found:411.0683.

[0092] Compound 34: 3-(5-(isopropylsulfonyl)-1-oxo-3-propionyl-2,3-dihydro-1,3,4-thiadiazole)-6-methyl-chromone: white solid, yield: 69.4%, mp 173.1-174.3; 1 H NMR (400MHz, CDCl3) δ8.34(s,1H),7.94(d,J=0.9Hz,1H),7.58(dd,J=8.6,2.2Hz,1H),7.45(d,J=8.6Hz,1H),6.0 6(s,1H),3.69(dt,J=13.8,6.9Hz,1H),2.94-2.81(m,2H),2.47(s,3H),1.65-1.61(m,6H),1.17(t,J=7.4Hz,3H). 13 C NMR (100MHz, CDCl3) δ175.39,173.70,157.49,154.60,152.99,136.56,136.32,125.24, 122.38,118.19,117.77,85.92,57.35,28.00,20.98,15.25,14.95,8.22.HR-MS(ESI)m / z Calcd.For C 18 H 21 N₂O₆S₂([M+H)) + ):425.0836,Found:425.0832.

[0093] Compound 35: 3-(3-acetyl-5-(methanesulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-7-fluoro-chromone: white solid, yield: 72.6%, mp 193.4-193.7; 1 H NMR (400MHz, CDCl3) δ8.37(s,1H),8.15(dd,J=8.9,6.1Hz,1H),7.22(ddd,J=18.6,8.8,2.3Hz,2H),6.09(s,1H),3.48(s,3H),2.49(s,3H). 13C NMR (100MHz, CDCl3) δ174.58(s), 170.24(s), 166.33(d,J=258.5Hz), 157.99(s), 157.30(d,J=13.5Hz), 154.92(s), 128.66(d,J =10.8Hz),119.55(s),118.43(s),115.43(d,J=23.0Hz),105.33(d,J=25.6Hz),85.46(s),45.23(s),22.30(s).HR-MS(ESI)m / z Calcd.For C 14 H 12 FN2O6S2([M+H) + ):387.0115,Found:387.0126.

[0094] Compound 36: 3-(3-acetyl-5-(methanesulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-6,8-dibromochromone: white solid, yield: 47.2%, mp 239.6-240.3; 1 H NMR (400MHz, CDCl3) δ8.48(s,1H),8.23(d,J=2.3Hz,1H),8.12(d,J=2.3Hz,1H),6.11(s,1H),3.50(s,3H),2.52(s,3H). 13 C NMR (100MHz, CDCl3) δ174.00,170.20,157.82,154.97,151.98,140.93,127.96,124.71,119.98,118.53,113.42,85.21,45.29,22.27.HR-MS(ESI)m / z Calcd.ForC 14 H 11 Br2N2O6S2([M+H] + ):524.8420,Found:524.8412.

[0095] Compound 37: 3-(3-acetyl-5-(methanesulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-6,8-dichloro-chromone: white solid, yield: 63.8%, mp 242.9-243.3; 1 H NMR (400MHz, CDCl3) δ8.45 (s, 1H), 8.01 (d, J = 2.4Hz, 1H), 7.81 (d, J = 2.4Hz, 1H), 6.09 (s, 1H), 3.48 (s, 3H), 2.50 (s, 3H).13 C NMR (100MHz, DMSO) δ174.32,170.18,159.25,154.42,150.73,135.06,131.02,124.92,124.45,123.86,117.61,84.45,45.63,22.62.HR-MS(ESI)m / z Calcd.For C 14 H 11 Cl2N2O6S2([M+H) + ):436.9430,Found:436.9480.

[0096] Compound 38: 3-(3-acetyl-5-(methanesulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-7-methyl-chromone: white solid, yield: 77.4%, mp 200.7-201.6; 1 H NMR (400MHz, CDCl3) δ8.36(s,1H),8.00(d,J=8.2Hz,1H),7.35(s,1H),7.29(d,J=8.1Hz,1H),6.10(s,1H),3.51(s,3H),2.52(s,3H),2.50(s,3H). 13 C NMR (100MHz, CDCl3) δ175.29,170.22,157.57,156.43,154.92,147.01,127.94, 125.64,120.34,118.14,85.78,45.20,22.32,22.03.HR-MS(ESI)m / zCalcd.For C 15 H 15 N₂O₆S₂([M+H)) + ):383.0366,Found:383.0363.

[0097] Compound 39: 3-(3-acetyl-5-(isopropylsulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-7-methyl-chromone: white solid, yield: 81.7%, mp 194.1-195.3; 1H NMR (400MHz, CDCl3) δ8.33(s,1H),8.00(d,J=8.2Hz,1H),7.32(s,1H),7.26(d,J=8.2Hz,1H),6.07(s,1H ),3.68(dt,J=13.7,6.9Hz,1H),2.51(s,3H),2.47(s,3H),1.60(d,J=6.9Hz,3H),1.58(d,J=6.9Hz,3H). 13 C NMR (100MHz, CDCl3) δ175.18,170.20,157.39,156.42,153.30,146.86,127.84,125.71,12 0.41,118.10,117.79,85.67,57.34,22.32,22.01,15.24,14.93.HR-MS(ESI)m / zCalcd.For C 17 H 19 N₂O₆S₂([M+H)) + ):411.0679,Found:411.0674.

[0098] Compound 40: 3-(3-acetyl-5-(isopropylsulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-7-fluoro-chromone: white solid, yield: 74.9%, mp 192.5-193.6; 1 H NMR (400MHz, CDCl3) δ8.38 (s, 1H), 8.16 (dd, J = 8.8, 6.1Hz, 1H), 7.27-7.15 (m, 2H), 6 .10(s,1H),3.66(dt,J=13.8,6.9Hz,1H),2.48(s,3H),1.59(dd,J=8.7,7.0Hz,6H). 13 C NMR (100MHz, CDCl3) δ174.49, 170.22, 166.24 (d, J = 257.9Hz), 157.92, 157.29 (d, J = 13.5Hz), 153.29, 128.70 (d, J = 10.8Hz), 1 19.61(d,J=2.2Hz),118.12,115.29(d,J=23.0Hz),105.28(d,J=25.6Hz),85.31,57.36,22.30,15.20,14.94.HR-MS(ESI)m / z Calcd.For C 16 H 16 FN2O6S2([M+H) +):415.0428,Found:415.0423.

[0099] Compound 41: 3-(3-acetyl-5-(isopropylsulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-6,8-dichloro-chromone: white solid, yield: 73.5%, mp 214.7-215.2; 1 H NMR (400MHz, CDCl3) δ8.42(s,1H),8.02(d,J=2.5Hz,1H),7.79(d,J=2.5Hz,1H),6.07(s,1H ),3.64(dt,J=13.7,6.9Hz,1H),2.48(s,3H),1.60(d,J=7.3Hz,3H),1.58(d,J=7.4Hz,3H). 13 C NMR (100MHz, CDCl3) δ173.95,170.20,157.64,153.36,150.64,135.19,132.24,12 4.98,124.54,124.09,118.28,85.07,57.44,22.27,15.20,14.98.HR-MS(ESI)m / z Calcd.For C 16 H 15 Cl2N2O6S2([M+H) + ):464.9743,Found:464.9732.

[0100] Compound 42: 3-(3-acetyl-5-(isopropylsulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-6,8-dibromochromone: white solid, yield: 77.3%, mp 227.3-228.1; 1 H NMR (400MHz, CDCl3) δ8.45(s,1H),8.25(d,J=2.3Hz,1H),8.12(d,J=2.3Hz,1H),6.08(s,1H ),3.67(dt,J=13.7,6.9Hz,1H),2.50(s,3H),1.62(d,J=7.7Hz,3H),1.60(d,J=7.3Hz,3H). 13 C NMR (100MHz, CDCl3) δ173.89,170.19,157.66,153.43,151.99,140.83,128.02,12 4.78,119.89,118.27,113.36,85.08,57.45,22.28,15.20,15.00.HR-MS(ESI)m / z Calcd.For C16 H 15 Br2N2O6S2([M+H] + ):552.8733,Found:552.8715.

[0101] Compound 43: 3-(3-acetyl-5-(isopropylsulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-8-bromo-6-chloro-chromone: white solid, yield: 75.9%, mp 223.6-223.9; 1 H NMR (400MHz, CDCl3) δ8.43(s,1H),8.07(d,J=2.3Hz,1H),7.96(d,J=2.4Hz,1H),6.07(s,1H ),3.65(dt,J=13.7,6.8Hz,1H),2.49(s,3H),1.60(d,J=7.5Hz,3H),1.59(d,J=7.6Hz,3H). 13 C NMR (100MHz, CDCl3) δ174.03,170.20,157.66,153.42,151.59,138.27,132.69 ,124.83,124.42,118.14,113.22,57.45,22.28,15.20,14.99.HR-MS(ESI)m / z Calcd.For C 16 H 15 BrClN2O6S2([M+H] + ):508.9238,Found:508.9219.

[0102] Compound 44: 3-(3-acetyl-5-(tert-butylsulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-6-bromo-chromone: white solid, yield: 64.9%, mp 168.5-168.7; 1 H NMR (400MHz, CDCl3) δ8.41(s,1H),8.23(d,J=2.4Hz,1H),7.85(dd,J=8.9,2.4Hz,1H),7.47(d,J=8.9Hz,1H),6.10(s,1H) ,3.55(ddd,J=8.9,6.1,3.6Hz,2H),2.49(s,3H),2.09-1.93(m,2H),1.59(dq,J=14.8,7.4Hz,2H),1.03(t,J=7.4Hz,3H). 13C NMR (100MHz, CDCl3) δ174.37,170.22,158.18,155.01,154.18,138.08,128.47,123.9 5,120.48,119.87,118.19,85.28,56.91,23.80,22.32,21.58,13.62.HR-MS(ESI)m / z Calcd.For C 16 H 15 BrClN2O6S2([M+H] + ):488.9784,Found:488.9796.

[0103] Compound 45: 3-(3-acetyl-5-(tert-butylsulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-6,8-dibromochrome:

[0104] White solid, yield: 71.5%, mp 194.4-196.0; 1 H NMR (400MHz, CDCl3) δ8.46(s,1H),8.19(d,J=2.3Hz,1H),8.09(d,J=2.3Hz,1H),6.11(s,1H),3.59 -3.47(m,2H),2.49(s,3H),2.07-1.95(m,2H),1.56(dt,J=14.8,7.4Hz,2H),1.01(t,J=7.4Hz,3H). 13 C NMR (100MHz, CDCl3)δ

[0105] 173.99,170.22,158.01,154.27,151.96,140.75,127.91,124.77,119.80, 118.37,113.39,85.00,56.98,23.79,22.32,21.59,13.63.HR-MS(ESI)m / z Calcd.For:C 17 H 17 Br2N2O6S2([M+H] + ):566.8889,Found:566.8873.

[0106] Compound 46: 3-(3-acetyl-5-(tert-butylsulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-6,8-dichloro-chromone

[0107] White solid, yield: 73.1%, mp 194.3-195.6; 1H NMR (400MHz, CDCl3) δ8.45(s,1H),7.99(d,J=2.5Hz,1H),7.80(d,J=2.5Hz,1H),6.10(s,1H),3.56 -3.48(m,2H),2.49(s,3H),2.06-1.96(m,2H),1.57(dd,J=15.0,7.5Hz,2H),1.01(t,J=7.4Hz,3H). 13 C NMR (100MHz, CDCl3) δ174.07,170.26,158.04,154.14,150.63,135.12,132.13,124.99,124 .53,123.96,118.40,84.98,56.94,23.79,22.30,21.57,13.61.HR-MS(ESI)m / zCalcd.For:C 17 H 17 Cl2N2O6S2([M+H) + ):478.9900,Found:478.9899.

[0108] Compound 47: 3-(3-acetyl-5-(tert-butylsulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-8-bromo-6-chloro-chromone: white solid, yield: 77.4%, mp 201.8-202.9; 1 H NMR (400MHz, CDCl3) δ8.45(s,1H),8.03(d,J=2.2Hz,1H),7.96(d,J=2.3Hz,1H),6.10(s,1H),3.60 -3.47(m,2H),2.49(s,3H),2.12-1.90(m,2H),1.57(dq,J=14.8,7.5Hz,2H),1.01(t,J=7.4Hz,3H). 13 C NMR (100MHz, CDCl3) δ174.13,170.22,158.03,154.24,151.57,138.19,132.58,124.70,124 .41,118.26,113.25,85.00,56.97,23.80,22.32,21.58,13.62.HR-MS(ESI)m / zCalcd.For:C 17 H 17 BrClN2O6S2([M+H] + ):522.9394,Found:522.9391.

[0109] Compound 48: 3-(3-acetyl-5-(tert-butylsulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-6-fluoro-chromone: white solid, yield: 81.8%, mp 170.1-170.5; 1 H NMR (400MHz, CDCl3) δ8.39(s,1H),7.74(dd,J=7.8,3.0Hz,1H),7.59(dd,J=9.2,4.1Hz,1H),7.53-7.47(m,1H),6. 08(s,1H),3.65-3.44(m,2H),2.49(s,3H),2.13-1.93(m,2H),1.58(dd,J=14.9,7.4Hz,2H),1.02(t,J=7.4Hz,3H). 13 C NMR (100MHz, CDCl3) δ174.87, 170.23, 159.96 (d, J = 249.5Hz), 158.08 (s), 154.19, 152.54, 123.91 (d, J = 7.8Hz), 123.51 (d, J = 25. 5Hz),120.86(d,J=8.2Hz),117.49,110.80(d,J=24.1Hz),85.38,56.94,23.83,22.32,21.57,13.60.HR-MS(ESI)m / zCalcd.For:C 17 H 18 N₂O₆S₂([M+H)) + ):429.0585,Found:429.0577.

[0110] Compound 49: 3-(3-acetyl-5-(tert-butylsulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-6-chloro-chromone: white solid, yield: 71.8%, mp 169.3-169.5; 1 H NMR (400MHz, CDCl3) δ8.38 (s, 1H), 8.07 (d, J = 2.5Hz, 1H), 7.71 (dd, J = 9.0, 2.6Hz, 1H), 7.53 (d, J = 9.0Hz, 1H) ,6.07(s,1H),3.60-3.49(m,2H),2.49(s,3H),2.11-1.89(m,2H),1.60-1.48(m,2H),1.02(t,J=7.4Hz,3H). 13C NMR (100MHz, CDCl3) δ174.51,170.23,158.16,154.58,154.17,135.34,132.39,125.24,123 .61,120.30,118.10,85.30,56.91,23.81,22.31,21.58,13.61.HR-MS(ESI)m / zCalcd.For:C 17 H 18 ClN2O6S2([M+H) + ):445.0289,Found:445.0269.

[0111] Compound 50: 3-(3-acetyl-5-(cyclohexylsulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-6-bromo-chromone: white solid, yield: 73.2%, mp 180.2-180.6; 1 H NMR (400MHz, CDCl3) δ8.37(s,1H),8.24(d,J=2.4Hz,1H),7.84(dd,J=8.9,2.4Hz,1H),7.46(d,J=8.9Hz,1H),6.05(s,1H),3.41(tt,J=1 2.1,3.3Hz,1H),2.48(s,3H),2.44-2.30(m,2H),2.01(dd,J=12.2,9.7Hz,2H),1.83-1.66(m,3H),1.38(dtt,J=15.6,12.7,6.3Hz,3H). 13 C NMR (100MHz, CDCl3) δ174.28,170.24,157.99,155.01,153.23,138.07,128.52,123.99,1 20.45,119.86,118.07,85.33,64.85,25.11,25.09,24.95,24.55,22.35.HR-MS(ESI)m / z Calcd.For:C 19 H 20 BrN2O6S2([M+H] + ):514.9941,Found:514.9931.

[0112] Compound 51: 3-(3-acetyl-5-(cyclohexylsulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-6,8-dibromochromone: white solid, yield: 37.5%, mp 169.1-170.3; 1H NMR (400MHz, CDCl3) δ8.44(s,1H),8.19(d,J=2.2Hz,1H),8.09(d,J=2.2Hz,1H),6.08(s,1H),3.42-3.3 3(m,1H),2.49(s,3H),2.37(t,J=14.0Hz,2H),2.05-1.93(m,2H),1.81-1.67(m,3H),1.44-1.28(m,3H). 13 C NMR (100MHz, CDCl3) δ173.87,170.18,157.71,153.48,151.98,140.76,127.98,124.82,1 19.82,118.22,113.34,85.02,64.95,53.50,25.09,24.89,24.66,22.29.HR-MS(ESI)m / z Calcd.For:C 19 H 19 Br2N2O6S2([M+H] + ):592.9046,Found:592.9026.

[0113] Compound 52: 3-(3-acetyl-5-(cyclohexylsulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-6,8-dichloro-chromone: white solid, yield: 65.6%, mp 191.9-192.8; 1 H NMR (400MHz, CDCl3) δ8.45 (s, 1H), 7.98 (d, J = 2.5Hz, 1H), 7.79 (d, J = 2.5Hz, 1H), 6.10 (s, 1H), 3.38 (tt, J = 12. 1,3.2Hz,1H),2.49(s,3H),2.37(t,J=15.0Hz,2H),2.05-1.96(m,2H),1.82-1.71(m,3H),1.44-1.29(m,3H). 13 C NMR (100MHz, CDCl3) δ173.95,170.21,157.68,153.38,150.64,135.15,132.19,124.98,124 .57,124.03,118.25,85.04,64.94,25.08,24.90,24.64,22.28.HR-MS(ESI)m / zCalcd.For:C 19 H 19 Cl2N2O6S2([M+H) + ):505.0056,Found:505.0053.

[0114] Compound 53: 3-(3-acetyl-5-(tert-butylsulfonyl)-1-oxo-2,3-dihydro-1,3,4-thiadiazole)-6-bromo-chromone: white solid, yield: 76.2%, mp 217.1-218.5; 1 H NMR (400MHz, CDCl3) δ8.45(s,1H),8.22(d,J=2.2Hz,1H),8.08(d,J=2.2Hz,1H),6.07(s,1H),2.47(s,3H),1.63(s,9H). 13 CNMR(100MHz,CDCl3)δ173.77,170.21,157.79,153.06,151.99,140.69,128.0 1,124.84,119.75,118.18,113.30,85.21,62.61,23.21,22.22.HR-MS(ESI)m / z Calcd.For:C 17 H 18 BrN2O6S2([M+H] + ):488.9784,Found:488.9781.

[0115] Example 2

[0116] Using 2-hydroxyacetophenone (Formula III), dithiocarbamate (Formula IVb), and acetic anhydride as starting materials, the 5-sulfone-1,3,4-thiadiazole chromone compound (Formula II) was synthesized via the following synthetic route:

[0117]

[0118] R1, R2, R3, and R6 are shown in Table 3.

[0119] The specific steps are as follows:

[0120] Cyclization reaction: The preparation of 3-formylchromone with the structure shown in Formula VI is the same as in Example 1.

[0121] Preparation of dithiocarbamate (Formula IVb): The dithiocarbamate shown in Formula IVb was prepared by referring to the preparation method of dithiocarbamate (Formula IVa) in Example 1.

[0122] 2.5 mmol of 3-formylchrome ketone (Formula VI) was dissolved in 30 mL of anhydrous ethanol, and 2.5 mmol of dithiocarbamate (Formula IVb) was added. The mixture was heated to reflux and reacted for 4–5 h. The reaction solution was cooled, and a large amount of solid precipitated. The solid was filtered and the filter cake was dried. The dried filter cake was added to 5 mL of acetic anhydride and refluxed for 2 h. After cooling, the reaction solution was placed in a -20°C refrigerator overnight, precipitating a large amount of white flocculent solid. This was filtered, and the resulting filter cake (Formula VII) was dissolved in 20 mL of dichloromethane. The mixture was stirred in an ice bath, and 75% m-chloroperoxybenzoic acid (4.5 mmol) was added in portions. The reaction was carried out for 12 h, and the reaction process was monitored by TLC. After the reaction was completed, the white solid obtained by vacuum distillation of the reaction solution was completely dissolved in DMSO, and the temperature was raised to 100°C, reacting for 4 h. The reaction solution was then extracted with saturated brine and ethyl acetate. The organic phase was collected and extracted three times with saturated brine and ethyl acetate. Vacuum distillation of the organic phase yielded a white solid, which was recrystallized from a mixture of dichloromethane and ethanol at 0°C (V2). 乙醇 :V 二氯甲烷 =4:1) to obtain the target compound shown in Formula II.

[0123] The compounds containing 5-sulfone-1,3,4-thiadiazole chromones, as shown in Formula II, are listed in Table 3.

[0124] Table 3. Compounds containing 5-sulfone-1,3,4-thiadiazole chromones

[0125]

[0126]

[0127] Compound 54: 3-(5-(methylsulfonyl)-1,3,4-thiadiazole)-chromone

[0128] White solid, yield: 93.6%, mp 218.3-219.5; 1 H NMR (400MHz, CDCl3) δ9.38(s,1H),8.38(dd,J=8.0,1.5Hz,1H),7.85(t,J=7.8Hz,1H),7.67(d,J=8.0Hz,1H),7.60(t,J=7.1Hz,1H),3.49(s,3H). 13 C NMR(100MHz,DMSO-d6)δ173.73,169.38,162.69,159.21,156.09,136.10,127.54,126.05,122.75,119.49,114.49,43.81.HR-MS(ESI)m / zCalcd.For:C 12 H9N2O4S2([M+H) +):308.9998,Found:308.9995.

[0129] Compound 55: 6-Bromo-3-(5-(methylsulfonyl)-1,3,4-thiadiazole)-chromone

[0130] White solid, yield: 96.1%, mp 20 3.0-20 4.2; 1 H NMR (400MHz, CDCl3) δ9.37 (s, 1H), 8.50 (d, J = 2.1Hz, 1H), 7.92 (d, J = 6.7Hz, 1H), 7.57 (d, J = 8.9Hz, 1H), 3.49 (s, 3H). 13 C NMR(100MHz,DMSO-d6)δ172.68,169.45,162.42,159.38,155.05,138.60,128.05,124.29,122.10,119.96,114.65,43.82.HR-MS(ESI)m / z Calcd.For:C 12 H8BrN2O4S2([M+H) + ):386.9103,Found:386.9107.

[0131] Compound 56: 6-Fluoro-3-(5-(Methylsulfonyl)-1,3,4-thiadiazole)-chromone

[0132] White solid, yield: 90.3%, mp 194.0-194.7; 1 H NMR (400MHz, CDCl3) δ9.39 (s, 1H), 8.02 (s, 1H), 7.70 (d, J = 10.4Hz, 1H), 7.58 (d, J = 10.1Hz, 1H), 3.49 (s, 3H). 13 C NMR(100MHz,DMSO-d6)δ173.29(s),169.45(s),162.59(s),159.40(s),155.80(d,J=631.1Hz),124.36(s) ),124.12(d,J=8.0Hz),122.48(d,J=8.7Hz),114.01(s),110.87(d,J=24.7Hz),43.81(s).HR-MS(ESI)m / z Calcd.For:C 12 H8FN2O4S2([M+H) + ):326.9904,Found:326.9895.

[0133] Compound 57: 6-chloro-3-(5-(methanesulfonyl)-1,3,4-thiadiazole)-chromone

[0134] White solid, yield: 89.5%, mp 199.8-200.6; 1 H NMR (400MHz, CDCl3) δ9.37 (s, 1H), 8.34 (d, J = 2.5Hz, 1H), 7.78 (dd, J = 8.9, 2.6Hz, 1H), 7.63 (d, J = 9.0Hz, 1H), 3.49 (s, 3H). 13 C NMR(100MHz,DMSO-d6)δ172.76,169.44,162.38,159.37,154.64,135.87,131.93,124.93,123.90,121.95,114.54,43.82.HR-MS(ESI)m / z Calcd.For:C 12 H8ClN2O4S2([M+H) + ):342.9609,Found:342.9616.

[0135] Compound 58: 6-Methyl-3-(5-(methanesulfonyl)-1,3,4-thiadiazole)-chromone

[0136] White solid, yield: 91.6%, mp 230.9-231.4; 1 H NMR (400MHz, CDCl3) δ9.36(s,1H),8.15(s,1H),7.65(d,J=8.6Hz,1H),7.56(d,J=8.6Hz,1H),3.49(s,3H),2.54(s,3H). 13 CNMR(100MHz,DMSO-d6)δ173.46,169.26,162.68,158.89,154.32,137.37,137.05,125.13,122.31,119.19,114.19,43.83,20.96.HR-MS(ESI)m / z Calcd.For:C 13 H 11 N₂O₄S₂([M+H)) + ):323.0155,Found:323.0155.

[0137] Compound 59: 7-Bromo-3-(5-(methylsulfonyl)-1,3,4-thiadiazole)-chromone

[0138] White solid, yield: 87.3%, mp 273.3-273.9;1 H NMR (400MHz, CDCl3) δ9.33 (s, 1H), 8.24 (d, J = 7.8Hz, 1H), 7.86 (s, 1H), 7.71 (d, J = 7.9Hz, 1H), 3.49 (s, 3H). 13 C NMR(100MHz,DMSO-d6)δ162.42,159.26,157.53,156.29,151.52,130.80,127.84,127.02,122.43,115.46,114.89,43.82.HR-MS(ESI)m / z Calcd.For:C 12 H8BrN2O4S2([M+H) + ):386.9103,Found:386.9109.

[0139] Compound 60: 3-(5-(ethylsulfonyl)-1,3,4-thiadiazole)-chromone

[0140] White solid, yield: 85.3%, mp 188.8-190.0; 1 H NMR (400MHz, CDCl3) δ9.39 (s, 1H), 8.38 (d, J = 8.0Hz, 1H), 7.85 (t, J = 7.8Hz, 1H), 7.67 (d,J=8.5Hz,1H),7.60(t,J=7.6Hz,1H),3.60(q,J=7.4Hz,2H),1.48(t,J=7.4Hz,3H). 13 C NMR (100MHz, DMSO-d6) δ173.71,167.83,163.00,159.22,156.07,136.11,127.55,126.05,122.73,119.49,114.54,50.24,7.44.HR-MS(ESI)m / z Calcd.For:C 13 H 11 N₂O₄S₂([M+H)) + ):323.0155,Found:323.0150.

[0141] Compound 6: 6-Bromo-3-(5-(ethylsulfonyl)-1,3,4-thiadiazole)-chromone

[0142] White solid, yield: 93.5%, mp 180.9-181.1; 1H NMR (400MHz, CDCl3) δ9.37 (s, 1H), 8.50 (d, J = 2.4Hz, 1H), 7.92 (dd, J = 8.9, 2.4Hz, 1H), 7.56 (d, J = 8.9Hz, 1H), 3.60 (q, J = 7.4Hz, 2H), 1.48 (t, J = 7.4Hz, 3H). 13 C NMR (100MHz, DMSO-d6) δ172.61,167.91,162.68,159.35,155.01,138.59,128.02,124.22,122.07,119.98,114.68,50.26,7.43.HR-MS(ESI)m / z Calcd.For:C 13 H 10 BrN2O4S2([M+H] + ):400.9260,Found:400.9259.

[0143] Compound 62: 3-(5-(ethylsulfonyl)-1,3,4-thiadiazole)-6-fluoro-chromone

[0144] White solid, yield: 90.1%, mp 186.4-187.1; 1 H NMR(400MHz, CDCl3) δ9.38(s,1H),8.01(dd,J=7.8,3.1Hz,1H),7.69(dd,J=9.2,4.1Hz ,1H),7.57(ddd,J=9.2,7.5,3.1Hz,1H),3.60(q,J=7.4Hz,2H),1.48(t,J=7.4Hz,3H). 13 C NMR(100MHz,DMSO-d6)δ173.18,167.88,162.84,160.14(d,J=246.6Hz),159.37,152.59,124.33,124.03( d,J=7.9Hz),122.45(d,J=8.7Hz),114.01,110.81(d,J=24.2Hz),50.24,7.42.HR-MS(ESI)m / zCalcd.For:C 13 H 10 FN2O4S2([M+H) + ):341.0061,Found:341.0064.

[0145] Compound 63: 6-chloro-3-(5-(ethylsulfonyl)-1,3,4-thiadiazole)-chromone

[0146] White solid, yield: 93.2%, mp 183.2-184.2; 1 H NMR (400MHz, CDCl3) δ9.37(s,1H),8.32(s,1H),7.78(dd,J=8.9,2.4Hz,1H),7.64(d,J=8.9Hz,1H),3.60(q,J=7.4Hz,2H),1.48(t,J=7.4Hz,3H). 13 C NMR (100MHz, DMSO-d6) δ172.74,167.92,162.68,159.36,154.62,135.87,131. 94,124.93,123.88,121.95,114.59,50.26,7.42.HR-MS(ESI)m / zCalcd.For:C 13 H 10 ClN2O4S2([M+H) + ):356.9765,Found:356.9765.

[0147] Compound 64: 3-(5-(ethylsulfonyl)-1,3,4-thiadiazole)-6-methyl-chromone

[0148] White solid, yield: 79.3%, mp 188.0-189.3; 1 H NMR (400MHz, DMSO-d6) δ9.65 (s, 1H), 8.00 (s, 1H), 7.77 (d, J = 10.8Hz, 2H), 3.74 (q, J = 7.3Hz, 2H), 2.47 (s, 3H), 1.30 (t, J = 7.3Hz, 3H). 13 C NMR(100MHz,DMSO-d6)δ173.59,167.71,163.09,158.95,154.38,137.47,1 25.15,124.72,122.36,119.25,114.30,50.27,20.98,7.41.HR-MS(ESI)m / z Calcd.For:C 14 H 13 ClN2O4S2([M+H) + ):337.0311,Found:337.0317.

[0149] Compound 65: 3-(5-(propionylsulfonyl)-1,3,4-thiadiazole)-chromone

[0150] White solid, yield: 93.7%, mp 191.3-192.7; 1H NMR (400MHz, CDCl3) δ9.38 (s, 1H), 8.38 (d, J = 8.1Hz, 1H), 7.85 (t, J = 8.7Hz, 1H), 7.67 (d, J = 8.1Hz, 1H),7.60(t,J=8.0Hz,1H),3.60-3.50(m,2H),1.95(dd,J=15.5,7.6Hz,2H),1.10(t,J=7.5Hz,3H). 13 C NMR(100MHz,DMSO-d6)δ173.71,168.32,162.98,159.20,156.07,136.09,12 7.53,126.04,122.72,119.48,114.54,56.85,16.47,12.89.HR-MS(ESI)m / z Calcd.For:C 14 H 13 N₂O₄S₂([M+H)) + ):337.0311,Found:337.0319.

[0151] Compound 66: 6-bromo-3-(5-(propionylsulfonyl)-1,3,4-thiadiazole)-chromone

[0152] White solid, yield: 90.8%, mp 179.3-180.7; 1 H NMR (400MHz, CDCl3) δ9.37(s,1H),8.50(s,1H),7.92(d,J=8.9Hz,1H),7.56(d,J=8 .9Hz,1H),3.60-3.49(m,2H),1.95(dq,J=15.2,7.5Hz,2H),1.10(t,J=7.4Hz,3H). 13 C NMR(100MHz,DMSO-d6)δ172.60,168.37,162.67,159.29,154.99,138.59,12 8.00,124.19,122.06,119.97,114.66,56.87,16.45,12.89.HR-MS(ESI)m / z Calcd.For:C 14 H 12 BrN2O4S2([M+H] + ):414.9416,Found:414.9419.

[0153] Compound 67: 6-Fluoro-3-(5-(propionylsulfonyl)-1,3,4-thiadiazole)-chromone

[0154] White solid, yield: 96.7%, mp 184.8-185.1; 1 H NMR (400MHz, CDCl3) δ9.38(s,1H),8.01(dd,J=7.8,3.0Hz,1H),7.69(dd,J=9.2,4.1Hz,1H),7.57(d dd,J=9.2,7.5,3.1Hz,1H),3.60-3.51(m,2H),1.95(dq,J=15.1,7.5Hz,2H),1.10(t,J=7.5Hz,3H). 13 C NMR(100MHz,DMSO-d6)δ173.17,168.37,162.84,160.15(d,J=246.1Hz),159.37,152.60,124.33,124.0 5(d,J=7.7Hz),122.46(d,J=9.1Hz),114.02,110.82(d,J=24.0Hz),56.84,16.46,12.89.HR-MS(ESI)m / z Calcd.For:C 14 H 12 FN2O4S2([M+H) + ):355.0217,Found:355.0223.

[0155] Compound 68: 6-chloro-3-(5-(propionylsulfonyl)-1,3,4-thiadiazole)-chromone

[0156] White solid, yield: 94.7%, mp 178.9-180.3; 1 H NMR (400MHz, CDCl3) δ9.37 (s, 1H), 8.34 (d, J = 2.5Hz, 1H), 7.78 (dd, J = 8.9, 2.6Hz, 1H), 7.6 3(d,J=8.9Hz,1H),3.60-3.50(m,2H),1.95(dq,J=15.1,7.5Hz,2H),1.10(t,J=7.5Hz,3H). 13 C NMR(100MHz,DMSO-d6)δ172.80,168.41,162.71,159.40,154.67,135.88,13 1.93,124.96,123.95,121.99,114.63,56.84,16.46,12.89.HR-MS(ESI)m / z Calcd.For:C 14 H 12 ClN2O4S2([M+H) +):370.9922,Found:370.9935.

[0157] Compound 69: 6-Methyl-3-(5-(propionylsulfonyl)-1,3,4-thiadiazole)-chromone

[0158] White solid, yield: 91.9%, mp 180.3-181.4; 1 H NMR (400MHz, CDCl3) δ9.37(s,1H),8.16(s,1H),7.66(dd,J=8.6,2.1Hz,1H),7.57(d,J=8.6H z,1H),3.61-3.51(m,2H),2.55(s,3H),1.96(dq,J=15.1,7.5Hz,2H),1.12(t,J=7.5Hz,3H). 13 C NMR(100MHz,DMSO-d6)δ173.52,168.23,163.01,158.95,154.36,137.40,137.0 8,125.15,122.36,119.23,114.30,56.86,20.98,16.47,12.90.HR-MS(ESI)m / z Calcd.For:C 15 H 15 N₂O₄S₂([M+H)) + ):351.0468,Found:351.0487.

[0159] Compound 70: 7-bromo-3-(5-(propionylsulfonyl)-1,3,4-thiadiazole)-chromone

[0160] White solid, yield: 88.5%, mp 214.7-215.7; 1 H NMR (400MHz, CDCl3) δ9.33 (s, 1H), 8.23 ​​(d, J = 8.5Hz, 1H), 7.86 (s, 1H), 7.71 (d, J = 8 .6Hz,1H),3.60-3.50(m,2H),1.94(dq,J=15.1,7.5Hz,2H),1.10(t,J=7.5Hz,3H). 13 C NMR(100MHz,DMSO-d6)δ173.35,168.45,162.74,159.26,156.22,130.80,12 9.21,127.81,122.44,121.99,114.91,56.84,16.47,12.89.HR-MS(ESI)m / z Calcd.For:C 14 H12 BrN2O4S2([M+H] + ):414.9416,Found:414.9434.

[0161] Compound 71: 3-(5-(isopropionylsulfonyl)-1,3,4-thiadiazole)-chromone

[0162] White solid, yield: 84.7%, mp 179.2-180.4; 1 H NMR (500MHz, CDCl3) δ10.65 (s, 1H), 8.96 (d, J = 1.0Hz, 1H), 8.25 (s, 1H), 7.72 (d ,J=7.6Hz,1H),7.54(d,J=8.9Hz,1H),3.72(tt,J=7.1,3.5Hz,1H),1.51(s,6H). 13 C NMR (100MHz, CDCl3) δ173.58,167.39,162.68,156.94,156.02,135.25,126.99,126.36,122.93,118.75,115.09,56.42,15.42.HR-MS(ESI)m / z Calcd.For:C 14 H 13 N₂O₄S₂([M+H)) + ):337.0311,Found:337.0324.

[0163] Compound 72: 6-Bromo-3-(5-(isopropanoylsulfonyl)-1,3,4-thiadiazole)-chromone

[0164] White solid, yield: 93.2%, mp 178.5-180.2; 1 H NMR (400MHz, DMSO-d6) δ9.70 (s, 1H), 8.21 (s, 1H), 8.07 (dd, J = 8.9, 2.1Hz, 1H), 7.84(d,J=8.9Hz,1H),3.90(dt,J=13.6,6.8Hz,1H),1.39(s,3H),1.37(s,3H). 13 C NMR (100MHz, DMSO-d6) δ172.49,166.77,162.90,159.27,154.92,138.57,127.96,124.11,122.02,119.99,114.68,56.29,15.41.HR-MS(ESI)m / z Calcd.For:C 14 H 12BrN2O4S2([M+H] + ):414.9416,Found:414.9434.

[0165] Compound 73: 6-Fluoro-3-(5-(isopropanoylsulfonyl)-1,3,4-thiadiazole)-chromone

[0166] White solid, yield: 94.7%, mp 194.5-195.9; 1 H NMR (400MHz, CDCl3) δ9.39 (s, 1H), 8.52 (d, J = 2.4Hz, 1H), 7.94 (dd, J = 8.9, 2.4Hz, 1 H),7.58(d,J=8.9Hz,1H),3.77(dt,J=13.8,6.9Hz,1H),1.52(s,3H),1.51(s,3H). 13 C NMR (100MHz, CDCl3) δ172.95,167.58,162.42,160.37(d,J=250.1Hz),156.98,152.29,124.28(d,J=8.0Hz ),123.54(d,J=25.3Hz),121.06(d,J=8.4Hz),114.64,111.43(d,J=24.2Hz),56.43,15.41.HR-MS(ESI)m / z Calcd.For:C 14 H 12 FN2O4S2([M+H) + ):355.0217,Found:355.0227.

[0167] Compound 74: 6-chloro-3-(5-(isopropionylsulfonyl)-1,3,4-thiadiazole)-chromone

[0168] White solid, yield: 89.7%, mp 189.2-190.1; 1 H NMR (400MHz, CDCl3) δ9.37 (s, 1H), 8.33 (d, J = 2.5Hz, 1H), 7.78 (dd, J = 8.9, 2.6Hz, 1 H),7.63(d,J=8.9Hz,1H),3.75(dt,J=13.8,6.9Hz,1H),1.50(s,3H),1.48(s,3H). 13C NMR (100MHz, DMSO) δ172.78,166.79,163.03,159.40,154.66,135.89,131.95,124.95,123.93,121.99,114.69,56.28,15.41.HR-MS(ESI)m / z Calcd.For:C 14 H 12 ClN2O4S2([M+H) + ):370.9922,Found:370.9889.

[0169] Compound 75: 3-(5-(isopropionylsulfonyl)-1,3,4-thiadiazole)-6-methyl-chromone

[0170] White solid, yield: 88.1%, mp 186.0-187.8; 1 H NMR (400MHz, CDCl3) δ9.38(s,1H),8.17(s,1H),7.66(d,J=6.6Hz,1H),7.57(d,J= 8.6Hz,1H),3.77(dt,J=13.7,6.9Hz,1H),2.56(s,3H),1.52(s,3H),1.50(s,3H). 13 C NMR(100MHz,DMSO-d6)δ173.56,173.45,166.60,163.37,159.01,154.39,137.4 4,137.12,125.17,122.39,119.27,114.39,56.25,20.99,15.41.HR-MS(ESI)m / z Calcd.For:C 15 H 15 N₂O₄S₂([M+H)) + ):351.0468,Found:351.0479.

[0171] Compound 76: 7-Bromo-3-(5-(isopropanoylsulfonyl)-1,3,4-thiadiazole)-chromone

[0172] White solid, yield: 83.7%, mp 226.0-227.8; 1 H NMR (400MHz, DMSO-d6) δ9.73 (s, 1H), 8.29 (s, 1H), 8.16 (d, J = 8.5Hz, 1H), 7. 85(d,J=8.6Hz,1H),3.90(dt,J=13.6,6.8Hz,1H),1.36(s,3H),1.34(s,3H). 13C NMR (100MHz, DMSO-d6) δ173.31,166.82,163.05,159.27,156.20,130.82,129. 22,127.80,122.43,121.96,114.97,56.28,15.41.HR-MS(ESI)m / zCalcd.For:C 14 H 12 BrN2O4S2([M+H] + ):414.9416,Found:414.9381.

[0173] Compound 77: 3-(5-(allylsulfonyl)-1,3,4-thiadiazole)-chromone

[0174] White solid, yield: 77.3%, mp 179.3-180.6; 1 H NMR(400MHz, DMSO-d6)δ9.69(s,1H),8.22(dd,J=8.0,1.4Hz,1H),7.95(t,J=7.0Hz,1H),7.85(d,J=8.2Hz,1H),7 .64(t,J=7.9Hz,1H), 5.87(ddt,J=17.3,10.1,7.3Hz,1H), 5.45(dd,J=16.7,13.6Hz,2H), 4.61(d,J=7.3Hz,2H). 13 C NMR(100MHz,DMSO-d6)δ173.61,167.47,163.05,159.16,155.98,136.03,127.47,1 26.70,125.97,124.41,122.63,119.41,114.41,59.78.HR-MS(ESI)m / zCalcd.For:C 14 H 11 N₂O₄S₂([M+H)) + ):335.0155,Found:335.0156.

[0175] Compound 78: 3-(5-(allylsulfonyl)-1,3,4-thiadiazole)-6-chloro-chromone

[0176] White solid, yield: 67.2%, mp 178.9-190.1; 1H NMR (400MHz, DMSO-d6) δ9.73 (s, 1H), 8.15 (d, J = 2.4Hz, 1H), 7.99 (dd, J = 9.0, 2.4Hz, 1H), 7.9 4(d,J=9.0Hz,1H),5.92-5.76(m,1H),5.42(dd,J=20.3,13.4Hz,2H),4.60(d,J=7.2Hz,2H). 13 C NMR(100MHz,DMSO-d6)δ172.77,167.55,162.85,159.43,154.63,135.86,131 .92,126.72,124.93,124.41,123.91,121.95,114.56,59.77.HR-MS(ESI)m / z Calcd.For:C 14 H 10 ClN2O4S2([M+H) + ):368.9765,Found:368.9734.

[0177] Compound 79: 3-(5-(allylsulfonyl)-1,3,4-thiadiazole)-6-methyl-chromone

[0178] White solid, yield: 84.2%, mp 176.7-178.2; 1 H NMR (400MHz, CDCl3) δ9.36 (s, 1H), 8.14 (s, 1H), 7.64 (d, J = 6.7Hz, 1H), 7.55 (d, J = 8.6Hz, 1H), 5 .91(dq,J=10.0,7.4Hz,1H),5.42(dd,J=31.0,13.6Hz,2H),4.28(d,J=7.4Hz,2H),2.53(s,3H). 13 C NMR(100MHz,DMSO-d6)δ173.58,167.41,163.20,159.08,154.39,137.42,137.11 ,126.69,125.17,124.45,122.39,119.26,114.27,59.77,20.99.HR-MS(ESI)m / z Calcd.For:C 15 H 13 N₂O₄S₂([M+H)) + ):349.0311,Found:349.0314.

[0179] Compound 80: 3-(5-(allylsulfonyl)-1,3,4-thiadiazole)-7-bromochromone

[0180] White solid, yield: 87.5%, mp 200.1-201.3; 1 H NMR (400MHz, CDCl3) δ9.36 (s, 1H), 8.25 (d, J = 8.5Hz, 1H), 7.88 (s, 1H), 7.73 (d, J = 7.0Hz, 1H), 5.92 (td, J=17.4, 7.4Hz, 1H), 5.43 (dd, J=32.0, 13.6Hz, 2H), 4.30 (d, J=7.4Hz, 2H). 13 C NMR(100MHz,DMSO-d6)δ173.34,167.63,162.67,159.31,156.21,130.80,129 .20,127.80,126.70,124.43,122.41,121.99,114.87,59.80.HR-MS(ESI)m / z Calcd.For:C 14 H 10 BrN2O4S2([M+H] + ):412.9260,Found:412.9226.

[0181] Compound 81: 3-(5-(benzylsulfonyl)-1,3,4-thiadiazole)-chromone

[0182] White solid, yield: 91.7%, mp 200.2-201.3; 1 H NMR (400MHz, CDCl3) δ9.37 (s, 1H), 8.34 (d, J = 6.7Hz, 1H), 7.83 (t, J = 7.1Hz, 1H) ,7.65(d,J=8.4Hz,1H),7.57(t,J=7.5Hz,1H),7.36-7.27(m,5H),4.80(s,2H). 13 C NMR(100MHz,DMSO-d6)δ173.67,167.60,163.25,159.30,156.06,136.09,131.84,129 .46,129.12,127.52,127.45,126.02,122.69,119.47,114.42,61.33.HR-MS(ESI)m / z Calcd.For:C 18 H 13 N₂O₄S₂([M+H)) + ):385.0311,Found:385.0330.

[0183] Compound 82: 3-(5-(benzylsulfonyl)-1,3,4-thiadiazole)-6-bromo-chromone

[0184] White solid, yield: 90.6%, mp 180.1-181.6; 1 H NMR (400MHz, CDCl3) δ9.36 (s, 1H), 8.45 (s, 1H), 7.90 (d, J = 6.6Hz, 1H), 7.55 (d, J = 8.9Hz, 1H), 7.36-7.28 (m, 5H), 4.80 (s, 2H). 13 CNMR(100MHz,DMSO-d6)δ172.66,167.68,163.01,159.48,155.05,138.59,131.84,129.47,1 29.12,128.04,127.41,124.27,122.08,119.94,114.61,61.32.HR-MS(ESI)m / zCalcd.For:C 18 H 12 BrN2O4S2([M+H] + ):462.9416,Found:462.9385.

[0185] Compound 83: 3-(5-(benzylsulfonyl)-1,3,4-thiadiazole)-6-fluoro-chromone

[0186] White solid, yield: 96.7%, mp 192.1-193.4; 1 H NMR (400MHz, CDCl3) δ9.37(s,1H),7.97(dd,J=7.8,3.0Hz,1H),7.68(dd,J=9.2,4.1Hz,1H),7.59-7.51(m,1H),7.35-7.28(m,5H),4.80(s,2H). 13 C NMR (100MHz, DMSO-d6) δ173.21, 167.63, 163.15, 160.13 (d, J = 246.5Hz), 159.50, 152.62, 131.83, 129.47, 129.12 ,127.43,124.32,124.06(d,J=7.9Hz),122.45(d,J=8.8Hz),113.93,110.84(d,J=24.3Hz),61.32.HR-MS(ESI)m / z Calcd.For:C 18 H 12 FN2O4S2([M+H) +):403.0217,Found:403.0214.

[0187] Compound 84: 3-(5-(benzylsulfonyl)-1,3,4-thiadiazole)-6-chloro-chromone

[0188] White solid, yield: 92.6%, mp 201.3-202.8; 1 H NMR (400MHz, CDCl3) δ9.38 (s, 1H), 8.31 (d, J = 2.5Hz, 1H), 7.78 (dd, J = 9.0, 2.5Hz, 1H), 7.64 (d, J = 8.9Hz, 1H), 7.38-7.30 (m, 5H), 4.82 (s, 2H). 13 C NMR(100MHz,DMSO-d6)δ172.78,167.68,163.00,159.49,154.66,135.86,131.91,131.84,1 29.47,129.12,127.41,124.96,123.92,121.95,114.52,61.33.HR-MS(ESI)m / zCalcd.For:C 18 H 12 ClN2O4S2([M+H) + ):418.9922,Found:418.9919.

[0189] Compound 85: 3-(5-(benzylsulfonyl)-1,3,4-thiadiazole)-6-methyl-chromone

[0190] White solid, yield: 95.1%, mp 194.6-195.2; 1 H NMR (400MHz, CDCl3) δ9.34(s,1H),8.10(s,1H),7.62(dd,J=8.6,1.8Hz,1H),7.53(d,J=8.6Hz,1H),7.31(s,5H),4.80(s,2H),2.51(s,3H). 13 C NMR (100MHz, DMSO-d6) δ173.42,167.53,163.25,158.98,154.30,137.36,137.04,131.85,129. 45,129.11,127.43,125.12,122.27,119.18,114.15,61.34,20.96.HR-MS(ESI)m / zCalcd.For:C 19 H 15 N₂O₄S₂([M+H))+ ):399.0468,Found:399.0472.

[0191] Compound 86: 3-(5-(benzylsulfonyl)-1,3,4-thiadiazole)-7-bromo-chromone

[0192] White solid, yield: 89.5%, mp 183.8-184.4; 1 H NMR (400MHz, CDCl3) δ9.32(s,1H),8.19(d,J=8.5Hz,1H),7.85(d,J=1.5Hz,1H),7.69(d,J=8.5Hz,1H),7.35-7.29(m,5H),4.80(s,2H). 13 C NMR(100MHz,DMSO-d6)δ173.33,167.71,163.01,159.37,156.22,131.82,130.77,129 .47,129.12,127.80,127.44,122.41,121.97,119.38,114.80,61.32.HR-MS(ESI)m / z Calcd.For:C 18 H 12 BrN2O4S2([M+H] + ):462.9416,Found:462.9416.

[0193] Compound 87: 6,8-dibromo-3-(5-(methanesulfonyl)-1,3,4-thiadiazole)-chromone

[0194] White solid, yield: 73.8%, mp 227.5-228.7; 1 H NMR (400MHz, DMSO-d6) δ9.83 (s, 1H), 8.55 (d, J = 2.3Hz, 1H), 8.31 (d, J = 2.3Hz, 1H), 3.68 (s, 3H). 13 C NMR(100MHz,DMSO-d6)δ172.56,169.67,162.15,159.32,152.12,140.75,127.78,125.35,119.86,114.98,114.05,43.83.HR-MS(ESI)m / z Calcd.For:C 12 H7Br2N2O4S2([M+H) + ):464.8208,Found:464.8209.

[0195] Compound 88: 7-Fluoro-3-(5-(Methylsulfonyl)-1,3,4-thiadiazole)-chromone

[0196] White solid, yield: 87.0%, mp 274.4-275.5; 1 H NMR (400MHz, DMSO-d6) δ9.75(s,1H),8.35(dd,J=8.0,6.5Hz,1H),7.94(d,J=9.5Hz,1H),7.58(t,J=9.6Hz,1H),3.67(s,3H). 13 CNMR(100MHz,DMSO-d6)δ173.05,169.57,166.07(d,J=254.2Hz),162.45,159.39,157.23(d,J=13.9Hz),1 29.04(d,J=11.0Hz),120.02,116.20(d,J=23.0Hz),114.71,106.54(d,J=26.1Hz),43.82.HR-MS(ESI)m / z Calcd.For:C 12 H8FN2O4S2([M+H) + ):326.9904,Found:326.9907.

[0197] Compound 89: 8-Bromo-6-chloro-3-(5-(methanesulfonyl)-1,3,4-thiadiazole)-chromone

[0198] White solid, yield: 86.3%, mp 224.8-226.2; 1 H NMR (400MHz, DMSO-d6) δ9.84(s,1H),8.47(s,1H),8.20(s,1H),3.68(s,3H). 13 C NMR(100MHz,DMSO-d6)δ172.68,169.65,162.14,159.35,151.78,138.26,132.02,124.97,124.72,114.87,113.93,43.81.HR-MS(ESI)m / z Calcd.For:C 12 H7BrClN2O4S2([M+H) + ):420.8714,Found:420.8715.

[0199] Compound 90: 3-(5-(isopropanoylsulfonyl)-1,3,4-thiadiazole)-7-methyl-chromone

[0200] White solid, yield: 93.1%, mp 213.0-214.2; 1 H NMR(400MHz,DMSO-d6)δ9.69(s,1H),8.13(d,J=8.1Hz,1H),7.71(s,1H),7.49(d,J =8.2Hz,1H),3.88(dt,J=13.5,6.8Hz,1H),2.53(s,3H),1.36(s,3H),1.34(s,3H). 13 C NMR(100MHz,DMSO-d6)δ166.62,163.33,158.94,156.16,150.78,147.47,12 8.89,125.77,120.41,118.98,114.45,56.25,21.83,15.41.HR-MS(ESI)m / z Calcd.For:C 15 H 15 N₂O₄S₂([M+H)) + ):351.0468,Found:351.0476.

[0201] Compound 91: 7-Fluoro-3-(5-(isopropanoylsulfonyl)-1,3,4-thiadiazole)-chromone

[0202] White solid, yield: 87.2%, mp 211.4-212.7; 1 H NMR (400MHz, DMSO-d6) δ9.76 (s, 1H), 8.34 (dd, J=8.9, 6.3Hz, 1H), 7.94 (dd, J=9.4, 2.1Hz, 1H),7.58(dd,J=11.9,5.5Hz,1H),3.90(dt,J=13.4,6.7Hz,1H),1.36(s,3H),1.34(s,3H). 13 C NMR (100MHz, DMSO-d6) δ173.03,166.87,166.07(d,J=255.0Hz),163.09,159.43,157.22(d,J=13.4Hz),129.03(d,J =11.1Hz),120.00,116.23(d,J=23.4Hz),114.82,106.55(d,J=26.4Hz),56.28,15.41.HR-MS(ESI)m / zCalcd.For:C 14 H 12 FN2O4S2([M+H) + ):355.0217,Found:355.0226.

[0203] Compound 92: 3-(5-(ethylsulfonyl)-1,3,4-thiadiazole)-7-methyl-chromone

[0204] White solid, yield: 79.8%, mp 232.1-233.5; 1 H NMR (400MHz, DMSO-d6) δ9.66 (s, 1H), 8.12 (d, J = 7.9Hz, 1H), 7.69 (s, 1H), 7.4 8(d,J=7.8Hz,1H),3.76(q,J=7.1Hz,2H),2.52(s,3H),1.30(t,J=7.2Hz,3H). 13 C NMR(100MHz,DMSO-d6)δ162.05,161.28,160.66,158.95,156.20,128.90,128.72, 125.80,122.88,120.49,118.98,50.26,21.84,7.44.HR-MS(ESI)m / zCalcd.For:C 14 H 13 N₂O₄S₂([M+H)) + ):337.0311,Found:337.0316.

[0205] Compound 93: 6-Bromo-3-(5-(Butylsulfonyl)-1,3,4-thiadiazole)-chromone

[0206] White solid, yield: 90.1%, mp 181.7-182.2; 1 H NMR (400MHz, DMSO-d6) δ9.75(s,1H),8.32(s,1H),8.13(d,J=8.9Hz,1H),7.89(d,J=8.9Hz,1H),3. 83-3.70(m,2H),1.71(dt,J=15.2,7.7Hz,2H),1.41(dq,J=14.6,7.2Hz,2H),0.88(t,J=7.3Hz,3H). 13 C NMR(100MHz,DMSO-d6)δ172.56,168.36,162.61,159.30,154.97,138.57,127.9 9,124.17,122.04,119.97,114.65,55.11,24.50,21.18,13.88.HR-MS(ESI)m / z Calcd.For:C 15 H 14 BrN2O4S2([M+H] +):428.9573,Found:428.9586.

[0207] Compound 94: 6,8-dibromo-3-(5-(butylsulfonyl)-1,3,4-thiadiazole)-chromone

[0208] White solid, yield: 87.9%, mp 179.1-180.4; 1 H NMR(400MHz,DMSO-d6)δ9.85(s,1H),8.57(s,1H),8.32(s,1H),3.84-3.71(m ,2H),1.72(dt,J=15.3,7.6Hz,2H),1.47-1.35(m,2H),0.88(t,J=7.3Hz,3H). 13 C NMR(100MHz,DMSO-d6)δ172.39,168.58,162.30,159.28,152.00,140.75,127.69,125 .17,119.91,114.95,114.04,55.11,24.49,21.19,13.89.HR-MS(ESI)m / zCalcd.For:C 15 H 13 Br2N2O4S2([M+H] + ):506.8678,Found:506.8662.

[0209] Compound 95: 3-(5-(butylsulfonyl)-1,3,4-thiadiazole)-6,8-dichloro-chromone

[0210] White solid, yield: 84.7%, mp 178.7-180.2; 1 H NMR(400MHz,DMSO-d6)δ9.84(s,1H),8.37(s,1H),8.16(s,1H),3.85-3.70(m,2H), 1.72(dt,J=15.2,7.6Hz,2H), 1.41(dq,J=14.6,7.3Hz,2H), 0.88(t,J=7.3Hz,3H). 13 C NMR(100MHz,DMSO-d6)δ172.44,168.62,162.29,159.15,150.68,135.37,131.6 8,124.97,124.76,124.13,115.01,55.10,24.50,21.18,13.87.HR-MS(ESI)m / z Calcd.For:C 15 H 13Cl2N2O4S2([M+H) + ):418.9688,Found:418.9695.

[0211] Compound 96: 3-(5-(butylsulfonyl)-1,3,4-thiadiazole)-6-chloro-chromone

[0212] White solid, yield: 89.5%, mp 182.5-184.2; 1 H NMR (400MHz, DMSO-d6) δ9.74(s,1H),8.17(s,1H),8.01(d,J=9.0Hz,1H),7.96(d,J=9.0 Hz,1H),3.86-3.66(m,2H),1.81-1.62(m,2H),1.48-1.34(m,2H),0.88(t,J=7.3Hz,3H). 13 C NMR(100MHz,DMSO-d6)δ172.81,168.38,162.72,159.41,154.68,135.88,131.9 3,124.96,123.95,121.99,114.64,55.09,24.51,21.16,13.87.HR-MS(ESI)m / z Calcd.For:C 15 H 14 ClN2O4S2([M+H) + ):385.0078,Found:385.0107. Example 3

[0213] Target compound bactericidal activity detection

[0214] Six common agricultural plant pathogenic fungi—*Botrytis cinerea* (strawberry gray mold), *Altemaria solani* (tomato early blight), *Rhizoctonia solani* (rice sheath blight), *Gibberella zeae* (wheat scab), *Colletotrichum orbiculare* (cucumber anthracnose), and *Alternaria alternata* (apple spot)—were used as experimental subjects. The mycelial growth rate method was used to preliminarily screen the antibacterial activity of the target compounds. Three common agricultural plant pathogenic bacteria—*Ralstonia solanacearum* (tobacco bacterial wilt), *Xanthomonas axonopodis pvcitri* (citrus canker), and *Xanthomonas oryzae pv oryzae* (rice bacterial blight)—were used as experimental subjects. The turbidimetric method was used to preliminarily screen the antibacterial activity of the target compounds. Commonly used commercial fungicides for controlling the corresponding crop diseases and commercial fungicides with certain structural similarities to the target compound, such as tebuconazole, carbendazim, and cyprodinil, were selected as control agents.

[0215] Experimental equipment included: petri dishes (Hefei Xinenyuan Biotechnology Co., Ltd.), autoclave (TOMY SX-700), electric thermostatic biochemical incubator (Shanghai Jinghong Experimental Equipment Co., Ltd.), eppendrof pipette, double-sided clean bench for two people (Suzhou Purification Equipment Co., Ltd.), hole punch, turbidimeter, etc.

[0216] Experimental methods:

[0217] (I) Preliminary screening of the antifungal activity of 96 target compounds was conducted using the mycelial growth rate method.

[0218] Preparation of Potato Dextrose Agar (PDA) medium: Peel potatoes, weigh 200g, slice them, and boil them in about 1000mL of water for about 30 minutes. At this point, the potatoes should be cooked until soft but not mushy. Filter the medium through two layers of gauze into a graduated cylinder to remove the residue. Add water to 1000mL, add 18g of agar to the filtrate, and boil until dissolved. Add 20g of glucose, stir well, dispense into Erlenmeyer flasks, and sterilize at 121℃ and 1MPa for 20 minutes.

[0219] Preparation of drug-containing culture medium: Accurately weigh 10 mg of the test compound (96 target compounds, commercial drug cyazofamid, osthol), dissolve in 2 mL of DMSO to prepare a 5 mg / mL solution. Pipette 0.1 mL of this solution into 50 mL of sterile PDA medium (DMSO final concentration approximately 0.2%), shake thoroughly to prepare a 10 μg / mL drug-containing culture medium. Pour this medium evenly into three 9 cm diameter sterile petri dishes. Use a culture medium prepared with an equal volume of 0.1 mL of DMSO as a blank control.

[0220] Measurement of EC 50 Preparation of other drug-containing culture media with different concentrations: Take 0.1 mL of a 5 mg / mL drug solution, take half (0.05 mL), and add 0.05 mL of DMSO. Add the resulting drug solution to 50 mL of sterile PDA medium and shake thoroughly to prepare a drug-containing culture medium with a concentration of 5 μg / mL. Take the remaining 5 mg / mL drug solution (0.05 mL), add 0.05 mL of DMSO, take half of the newly prepared drug solution, add 0.05 mL of DMSO, and add the resulting drug solution to 50 mL of sterile PDA medium. Shake thoroughly to prepare a drug-containing culture medium with a concentration of 2.5 μg / mL. Drug-containing culture media with concentrations of 1.25 μg / mL and 0.625 μg / mL are prepared by following the same steps.

[0221] The drug treatment group and the blank group were set up. The treatment method and the amount of solvent added were the same as those of the drug treatment group. The specific experimental data are shown in Table 4.

[0222] Inoculation and activity assay: Stored bacterial cultures were removed from a 4°C freezer and pre-activated twice in fresh, sterile PDA medium before use. Mycelial discs were prepared by punching holes at the edges of normally growing colonies using a 0.5cm inner diameter punch. These discs were then inoculated into the center of either the drug-containing medium plate or the blank medium plate (mycelium facing upwards) using an inoculation needle and incubated at 25°C. When the colonies on the blank medium reached approximately 2 / 3 of the plate diameter (i.e., a colony diameter of 6.5cm), the colony diameter was measured. Each colony diameter was measured twice using the cross-sectional method, and the average value (unit: cm) was calculated. Each treatment was performed in triplicate. The growth inhibition rate after drug treatment was calculated using the following formula:

[0223] Inhibition rate (%) = (Coronavirus diameter in the control group - Coronavirus diameter in the treated group) / (Coronavirus diameter in the control group - 0.5) × 100%

[0224] (II) The antibacterial activity of 86 target compounds was initially screened using the turbidimetric method.

[0225] Preparation of Nutrient Broth (NB) liquid culture medium: Take 1L of distilled water, add 3g of beef extract, 1g of yeast extract, 5g of peptone, and 10g of glucose, stir well, and adjust the pH of the system to 7 with sodium hydroxide solution (5M). Dispense into test tubes, 5mL per tube, cap each tube, wrap the mouth of the test tube with newspaper, place in an autoclave, and sterilize at 121℃ for 20min. Store for later use.

[0226] Nutrient Agar (NA) solid medium: In addition to NB liquid medium, 16 g / L of agar needs to be added.

[0227] Preparation of drug-containing culture medium: Accurately weigh 10 mg of the test compound (86 target compounds, commercial drug tebuconazole), dissolve it in 1 mL of DMSO to prepare a 10 mg / mL solution, pipette 25 μL and add it to 5 mL of sterile NB liquid medium (DMSO final concentration approximately 0.5%), shake thoroughly to prepare a drug-containing culture medium with a concentration of 50 μg / mL. Each drug was tested in triplicate, and its OD value (OD1) at 595 nm was measured using a microplate reader. The culture medium prepared by adding an equal amount of DMSO (25 μL) served as a blank control.

[0228] Measurement of EC 50 Preparation of other drug-containing culture media with different concentrations: Take 25 μL of drug solution with a concentration of 10 mg / mL, take half of it (12.5 μL), and add 12.5 μL of DMSO. Add the resulting drug solution to 5 mL of sterile NB liquid medium and shake thoroughly to prepare a drug-containing culture medium with a concentration of 25 μg / mL. Take the remaining drug solution with a concentration of 10 mg / mL (12.5 μL), add 12.5 μL of DMSO, take half of the newly prepared drug solution, add 12.5 μL of DMSO, and add the resulting drug solution to 5 mL of sterile NB liquid medium. Shake thoroughly to prepare a drug-containing culture medium with a concentration of 6.25 μg / mL. Drug-containing culture media with concentrations of 6.25 μg / mL and 3.125 μg / mL are prepared in the same manner as above.

[0229] Inoculation and Activity Assay: Stored bacterial strains were removed from a -80°C freezer and pre-activated twice consecutively in fresh, sterile NA solid medium before use. Freshly activated bacterial colonies were picked from the NA solid medium and placed in NB liquid medium. The medium was then incubated in a constant-temperature shaker at 28°C and 180 rpm until the logarithmic growth phase. Subsequently, 40 μL of the bacterial suspension (OD value 0.6 to 0.8) in the logarithmic growth phase was added to the drug-containing medium, and the mixture was incubated in a constant-temperature shaker at 28°C and 180 rpm for approximately 36 hours. The OD value (OD2) at 595 nm was then measured using a microplate reader, and the actual OD value produced by the bacteria (ΔOD = OD2 - OD1) was calculated. The inhibition rate (I) of the corresponding compound at different concentrations was then calculated based on the ΔOD values ​​obtained from the control group and the drug-treated group. The calculation formula is as follows:

[0230]

[0231] A blank control group was set up, with the same treatment method and amount of solvent added as the drug-treated group. The specific experimental data are shown in Table 5.

[0232] Table 4. Initial screening results of the antifungal activity of the target compound [inhibition rate η (%)] (test concentration 10 μg / mL)

[0233]

[0234]

[0235]

[0236] Table 5. Initial screening results of antibacterial activity of compounds [inhibition rate η (%)] (test concentration 50 μg / mL)

[0237]

[0238]

[0239] Note: Rs represents the fungus that causes bacterial wilt of tobacco, Xac represents the fungus that causes citrus canker, and Xoo represents the fungus that causes bacterial blight of rice.

[0240] Table 4 shows the fungicide test results for common agricultural fungi, and Table 5 shows the fungicide test results for common agricultural plant pathogenic bacteria. The following conclusions can be drawn:

[0241] 1. Compounds containing 5-sulfonyl-1,3,4-thiadiazole chromones have shown certain fungicidal activity against common agricultural fungi, with some exhibiting 100% inhibition. Moreover, their inhibitory activity against some fungi is significantly higher than that of commercial pesticides (carbendazim, cyprodinil).

[0242] 2. Using the mycelial growth rate method, compounds 1-96 showed significant inhibitory activity against *Rhizoctonia solani*, *Early Blight*, and *Anthracnose*. Most compounds exhibited inhibition rates exceeding 80% against *Rhizoctonia solani* at 10 μg / mL. Furthermore, in vivo antifungal activity tests against *Rhizoctonia solani* revealed that compound 2, at a concentration of 200 μg / mL, achieved an inhibition rate of 97.1%, higher than the inhibition rate of carbendazim against *Rhizoctonia solani* at the same concentration (94.5%), maintaining high efficacy against this pathogen.

[0243] 3. Turbidimetric assay showed that compounds 1-86 had significant inhibitory activity against rice bacterial blight and citrus canker. Most compounds showed better inhibitory effects against rice bacterial blight than tebuconazole, and 40 compounds showed inhibition of more than 80% at a concentration of 50 μg / mL.

[0244] 4. In Formula I, introducing a large, electronegative, hydrophobic group at the C-6 or C-7 position of the chromone ring is beneficial to improving the inhibitory activity of the target compound against rice sheath blight pathogens; introducing a large group at the sulfone position is beneficial to improving the antibacterial activity of the target compound. Based on this characteristic, while maintaining the original molecular skeleton, large electron-withdrawing groups such as fluorine, chlorine, and bromine atoms are introduced into the 6- and 7-positions of the chromone ring in the form of mono- or poly-substitution, and relatively large alkyl substituents such as n-butyl, tert-butyl, and cyclohexyl are introduced into the sulfone position.

[0245] 5. In Formula II, introducing bulky groups to the C-6 and C-7 positions of the chromone is beneficial to improving its inhibitory activity against rice sheath blight pathogens; introducing electron-withdrawing groups to the 6-position of the chromone is beneficial to improving its inhibitory activity against rice sheath blight pathogens; introducing bulky alkyl groups to the sulfone position is beneficial to improving the antibacterial activity of the target compound. Based on this characteristic, while maintaining the original molecular skeleton, bulky electron-withdrawing groups such as fluorine, chlorine, and bromine atoms are introduced into the 6- and 7-positions of the chromone ring in the form of mono- or poly-substitution, and relatively bulky alkyl substituents such as n-butyl and isopropyl are introduced into the sulfone position.

[0246] 6. Overall, the introduction of large-volume and highly electronegative hydrophobic groups at the 6 and 7 positions of chromone exhibits good broad-spectrum fungicidal activity. It shows excellent fungicidal activity against rice sheath blight, strawberry gray mold, wheat scab, tomato early blight, cucumber anthracnose, and apple spot, with inhibition rates comparable to or better than the control drugs carbendazim and cyazofamid.

[0247] For compounds exhibiting inhibition rates above 70% in the initial in vitro activity screening, the EC50 of the tested pathogens was further determined using concentration gradients of 10, 5, 2.5, 1.25, and 0.625 μg / mL. 50 The values ​​obtained are calculated using the DPS data processing system, EC 50The values ​​are shown in Tables 6 and 7. For compounds with an inhibition rate of over 80% in the initial in vitro activity screening, the EC50 of the tested pathogens was further determined using concentration gradients of 50, 25, 12.5, 6.25, and 3.125 μg / mL. 50 The values ​​obtained are calculated using the DPS data processing system, EC 50 The values ​​are shown in Table 8.

[0248] Table 6. EC50 of some molecules against tested fungi 50 (μg / mL) Results

[0249]

[0250] Table 7. Antibacterial activity of some compounds against rice sheath blight pathogen EC 50 (μg / mL) Results

[0251]

[0252]

[0253] Table 8. Antibacterial activity of some compounds against rice bacterial blight pathogen EC 50 (μg / mL) Results

[0254]

[0255] From Tables 6, 7, and 8, we can draw the following conclusions:

[0256] 1. Compounds containing 5-sulfone-1,3,4-thiadiazole chromones showed good EC activity against common agricultural fungi. 50 Value, and EC 50 The value should be lower than that of commercial pesticides (carbendazim, cyprodinil). Compound 2 (against EC of rice sheath blight pathogen) 50 The antibacterial activity was most prominent with 0.41 μg / mL of carbendazim, compared to that of EC. 50 =0.43 μg / mL); compounds 4, 6, 8, 10, 13-15, 19, 21 also showed good inhibitory activity, EC 0.43. 50 The values ​​were all less than 1 μg / mL.

[0257] 2. Compounds containing 5-sulfone-1,3,4-thiadiazole chromones showed good EC activity against common agricultural bacteria. 50 Further research revealed that target compounds 1, 3, 7, 9, 13, and 14 showed good inhibitory effects against rice bacterial blight pathogens, EC 14. 50 The values ​​were all less than 10 μg / mL, which was superior to that of tebuconazole (70.89 μg / mL).

Claims

1. Chromone compounds containing 5-sulfone-1,3,4-thiadiazole, with the structure shown in Formula V: ； in, R1 is selected from H, F, Cl, Br, and methyl; R2 is selected from H, F, Br, and methyl; R3 is selected from H, Cl, and Br; R is selected from , ; R4 is selected from C1-C6 straight-chain or branched alkyl, cyclohexyl, allyl, and benzyl; R5 is selected from C1-C6 straight-chain or branched alkyl. R6 is selected from C1-C6 straight-chain or branched alkyl, allyl, and benzyl groups.

2. The chromone compound containing 5-sulfone-1,3,4-thiadiazole according to claim 1, characterized in that: R1 is selected from H, F, Cl, Br, and methyl; R2 is selected from H, F, Br, and methyl; R3 is selected from H, Cl, and Br; R4 is selected from C1-C4 straight-chain or branched alkyl, cyclohexyl, allyl, and benzyl; R5 is selected from C1-C2 alkyl; and R6 is selected from C1-C4 straight-chain or branched alkyl, allyl, and benzyl.

3. Chromone compounds containing 5-sulfone-1,3,4-thiadiazole, with structures as shown in Formula V: ； in, R is selected from , ; R is selected from In this case, R1 is selected from H, R2 is selected from H, R3 is selected from H, R4 is selected from C1 to C4 straight-chain alkyl, and R5 is selected from C1 to C2 alkyl; R1 is selected from F, R2 is selected from H, R3 is selected from H, R4 is selected from isopropyl, and R5 is selected from ethyl. R1 is selected from Cl, R2 is selected from H, R3 is selected from H, R4 is selected from C1 to C4 straight-chain or branched alkyl groups, and R5 is selected from methyl or ethyl. R1 is selected from Cl, R2 is selected from H, R3 is selected from Cl, R4 is selected from methyl, isopropyl, cyclohexyl, and R5 is selected from methyl; R1 is selected from Cl, R2 is selected from H, R3 is selected from bromine, R4 is selected from isopropyl, and R5 is selected from methyl. R1 is selected from Br, R2 is selected from H, R3 is selected from Cl, R4 is selected from C1-C4 straight-chain or branched alkyl or cyclohexyl, and R5 is selected from methyl. R1 is selected from Br, R2 is selected from F and Br, R3 is selected from H, R4 is selected from methyl and isopropyl, and R5 is selected from methyl. R is selected from In this case, R1 is selected from H, R2 is selected from H, R3 is selected from H, and R6 is selected from ethyl, isopropyl, and allyl. R1 is selected from H, R2 is selected from methyl, R3 is selected from H, and R6 is selected from ethyl or isopropyl. R1 is selected from methyl, R2 is selected from H, R3 is selected from H, and R6 is selected from n-propyl and isopropyl. R1 is selected from H, R2 is selected from Br, R3 is selected from H, and R6 is selected from n-propyl, isopropyl, and allyl. R1 is selected from H, R2 is selected from F, R3 is selected from H, and R6 is selected from methyl or isopropyl. R1 is selected from F, R2 is selected from H, R3 is selected from H, and R6 is selected from ethyl, n-propyl, and isopropyl. R1 is selected from Cl and Br, R2 is selected from H, R3 is selected from H, and R6 is selected from methyl, ethyl, n-propyl, isopropyl, and n-butyl. R1 is selected from Cl, R2 is selected from H, R3 is selected from H, and R6 is selected from allyl; R1 is selected from Cl, R2 is selected from H, R3 is selected from Cl, and R6 is selected from n-butyl. R1 is selected from Br, R2 is selected from H, R3 is selected from Br, and R6 is selected from methyl.

4. Chromone compounds containing 5-sulfone-1,3,4-thiadiazole, with structures as shown in Formula V: ； in, R is selected from R1, R2, R3, R4, and R5 are as follows: ； R is selected from R1, R2, R3, and R6 are as follows: 。 5. A method for preparing the 5-sulfone-1,3,4-thiadiazole chromone compound according to claim 1, characterized in that: When R is selected The synthesis route is as follows: ； Wherein, R1, R2, R3, R4, and R5 are as described in claim 1; When R is selected The synthesis route is as follows: ； R1, R2, R3, and R6 are as described in claim 1.

6. The method for preparing 5-sulfone-1,3,4-thiadiazole chromone compounds according to claim 5, characterized in that: When R is selected When, it includes the following steps: Step (1): Under ice bath conditions, POCl3 is slowly added to dry DMF while stirring. The temperature is maintained at 0-5℃ during the dropwise addition. After the dropwise addition is complete, the reaction is carried out for 1 hour to obtain VM reagent. o-hydroxyacetophenone of Formula III is added to VM reagent in batches, the temperature is raised to 50℃, the reaction is carried out for 2 hours, and then the temperature is raised to 80℃, the reaction is carried out for 4 hours. The reaction solution is filtered and the filter cake is dried to obtain 3-formylchrome ketone with the structure shown in Formula VI. The molar ratio of o-hydroxyacetophenone to phosphorus oxychloride is 1:

3. Step (2): Using anhydrous ethanol as the reaction solvent, 3-formyl chromone of formula VI and dithiocarbamate of formula IVa are reacted under reflux for 4-5 h; the reaction solution is cooled, filtered, and the filter cake is dried; the filter cake is then added to the acid anhydride of formula VIII and refluxed for 2 h; the reaction solution is cooled and kept at -20℃ overnight, filtered, and the filter cake is dissolved in dichloromethane. The mixture is stirred in an ice bath, and m-chloroperoxybenzoic acid is added in batches. The reaction is carried out for 12 h to obtain the target compound shown in formula I; wherein, the molar ratio of 3-formyl chromone to dithiocarbamate is 1:1; the molar ratio of 3-formyl chromone to m-chloroperoxybenzoic acid is 1:1.

8.

7. The method for preparing 5-sulfone-1,3,4-thiadiazole chromone compounds according to claim 5, characterized in that: When R is selected When, it includes the following steps: Step (1): Under ice bath conditions, POCl3 is slowly added to dry DMF while stirring. The temperature is maintained at 0-5℃ during the dropwise addition. After the dropwise addition is complete, the reaction is carried out for 1 hour to obtain VM reagent. o-hydroxyacetophenone of Formula III is added to VM reagent in batches, the temperature is raised to 50℃, the reaction is carried out for 2 hours, and then the temperature is raised to 80℃, the reaction is carried out for 4 hours. The reaction solution is filtered and the filter cake is dried to obtain 3-formylchrome ketone with the structure shown in Formula VI. The molar ratio of o-hydroxyacetophenone to phosphorus oxychloride is 1:

3. Step (2): Using anhydrous ethanol as the reaction solvent, 3-formyl chromone (Formula VI) and dithiocarbamate (Formula IVb) are reacted under reflux for 4-5 h. The reaction solution is cooled, filtered, and the filter cake is dried. The filter cake is then added to acetic anhydride and refluxed for 2 h. The reaction solution is cooled and kept at -20°C overnight. The filter cake is then filtered and dissolved in dichloromethane. The mixture is stirred in an ice bath, and m-chloroperoxybenzoic acid is added in batches. The reaction is carried out for 12 h. The solvent is removed by vacuum distillation of the reaction solution. The resulting solid is dissolved in DMSO and heated to 100°C for 4 h to obtain the target compound shown in Formula II. The molar ratio of 3-formyl chromone to dithiocarbamate is 1:1, and the molar ratio of 3-formyl chromone to m-chloroperoxybenzoic acid is 1:1.

8.

8. The use of the 5-sulfone-1,3,4-thiadiazole chromone compound 1 in claim 4 in the preparation of pesticide formulations for controlling rice sheath blight, strawberry gray mold, wheat scab, tomato early blight, cucumber anthracnose, apple spot, and rice bacterial blight; The compounds containing 5-sulfone-1,3,4-thiadiazole chromones in claim 4, namely 2, 5, 6, 8, 9, 10, 12, 13, 14, 15, 19, 23, 27, 31, 32, 33, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 6 Application of 6, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 87, 88, 89, 90, 91, 92, 93, 94, 95, and 96 in the preparation of pesticide formulations for the control of rice sheath blight, strawberry gray mold, wheat scab, tomato early blight, cucumber anthracnose, apple spot, rice bacterial blight, tobacco bacterial wilt, and citrus canker. The use of 5-sulfone-1,3,4-thiadiazole chromone compounds 3, 4, 7, 11, and 21 in claim 4 in the preparation of pesticide formulations for controlling rice sheath blight, strawberry gray mold, wheat scab, tomato early blight, cucumber anthracnose, apple spot, rice bacterial blight, and citrus canker. The use of the 5-sulfone-1,3,4-thiadiazole chromone compound 17 in claim 4 in the preparation of pesticide formulations for the control of rice sheath blight, strawberry gray mold, wheat scab, tomato early blight, cucumber anthracnose, rice bacterial blight and citrus canker. The use of the 5-sulfone-1,3,4-thiadiazole chromone compound 18 in claim 4 in the preparation of pesticide formulations for the control of rice sheath blight, strawberry gray mold, wheat scab, tomato early blight, cucumber anthracnose, apple spot, rice bacterial blight and citrus canker. The use of 5-sulfone-1,3,4-thiadiazole chromone compounds 20 and 26 in claim 4 in the preparation of pesticide formulations for the control of rice sheath blight, wheat scab, tomato early blight, cucumber anthracnose, apple spot, rice bacterial blight, tobacco bacterial wilt, and citrus canker. The use of 5-sulfone-1,3,4-thiadiazole chromone compounds 22 and 34 in claim 4 in the preparation of pesticide formulations for the control of rice sheath blight, strawberry gray mold, wheat scab, tomato early blight, cucumber anthracnose, apple spot, tobacco bacterial wilt and citrus canker. The use of the 5-sulfone-1,3,4-thiadiazole chromone compound 24 in claim 4 in the preparation of pesticide formulations for the control of rice sheath blight, strawberry gray mold, wheat scab, tomato early blight, cucumber anthracnose and citrus canker. The use of the 5-sulfone-1,3,4-thiadiazole chromone compound 25 in claim 4 in the preparation of pesticide formulations for the control of rice sheath blight, strawberry gray mold, wheat scab, tomato early blight, cucumber anthracnose, rice bacterial blight, tobacco bacterial wilt, and citrus canker. The use of the 5-sulfone-1,3,4-thiadiazole chromone compound 28 in claim 4 in the preparation of pesticide formulations for controlling strawberry gray mold, tomato early blight, apple spot, tobacco bacterial wilt, and citrus canker. The use of the 5-sulfone-1,3,4-thiadiazole chromone compound 30 in claim 4 in the preparation of pesticide formulations for controlling strawberry gray mold, rice sheath blight, tobacco bacterial wilt, and citrus canker. The use of the 5-sulfone-1,3,4-thiadiazole chromone compound 45 in claim 4 in the preparation of pesticide formulations for controlling strawberry gray mold, wheat scab, tomato early blight, cucumber anthracnose, apple spot, rice bacterial blight, tobacco bacterial wilt, and citrus canker.

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