Preparation method of novel sulfonate substance and application of composition of novel sulfonate substance in aspects of bacteriostasis and plant growth promotion

Abstract

The invention discloses a novel sulfonate substance, which is characterized in that the structural formula of the novel sulfonate substance is as follows: # imgabs0 #, and R is phenyl, substituted phenyl, heterocyclic ring or C2-C3 alkyl. A biological activity determination result shows that the sulfonate compound containing the thiazole and pyridine structure has medium to excellent inhibitory activity on the rice bacterial streak pathogen, the activity of the compound C28 is the best, and the inhibitory activity on the rice bacterial streak pathogen is 78.9% and is higher than that of control agents thiediazole copper and zinc thiazole.

Description

Technical Field

[0001] The invention relates to the field of chemical technology, in particular to a novel sulfonate plant growth regulator, a preparation method of the compound and use of the composition thereof on rice bacterial leaf streak pathogen, kiwi fruit bacterial canker pathogen and citrus canker pathogen. Background Art

[0002] At present, global warming has caused the pests and diseases in agricultural production to continue to worsen. Among bacterial diseases, rice, citrus, kiwifruit and other crop industries are deeply affected. They are notorious agricultural diseases in the world. Once infected, they are difficult to control, causing serious harm to crops and leading to crop yield reduction. At present, thiophanate-methyl (TC) and thiazolyl zinc (TZ) are mainly used to prevent and control bacterial diseases, but long-term and frequent use will lead to increased drug resistance and poor control effect. Therefore, there is an urgent need to develop a new highly active compound to control plant bacterial infections.

[0003] Plant growth regulators refer to a type of synthetic organic matter that produces plant hormones and side-effect substances, which can be used to improve crop resistance or improve crop quality. In the soil during the seedling stage of plant cultivation, a relatively large amount of natural plant growth regulators with low biological concentrations can fully take effect on several different plant effects, including inducing, prolonging seedlings, and effectively controlling the growth cycle of plant roots, which can fully achieve the multiple goals of promoting rapid rooting, flowering, increasing production, and improving soil resistance. In addition, plant growth regulators can indeed be used to effectively control and overcome major difficult cases in the field of agricultural cultivation and technology, especially for how plants can overcome seed dormancy, improve crop plant growth, and effectively overcome the growth conditions of genetically modified crops, and improve harvesting and storage conditions. At present, plant growth regulators have been used in the cultivation of roots and fish vines, and have achieved significant results.

[0004] Allicin has a unique spicy taste and strong smell, and is one of the main sources of garlic flavor. It not only gives garlic a unique flavor, but also gives it a variety of biological activities such as antibacterial, antiviral, and antioxidant. Regarding the chemical properties of allicin, its chemical name is propylene trisulfide, and its molecular formula is C 6 H 10 S 3 , molecular weight is 178.33. It is a light yellow oily liquid with a pungent odor. Allicin is composed of allicin and alliin, which together give garlic a unique pharmacological effect, inhibiting and killing a variety of bacteria and parasites in vitro.

[0005] Heterocyclic compounds have attracted people's attention due to their unique advantages such as good selectivity, good activity, low dosage and low toxicity. Its five-membered heterocyclic ring - 1,3,4-thiadiazole has a broad spectrum of biological activity and is widely used in the field of medicine and pesticides. It has bactericidal, fungicidal, antiviral, insecticidal and anti-tumor activities. In recent years, a number of commercial drugs containing thiadiazole structures have been successfully developed, such as chlorpyrifos, thiophanate-methyl, thiophanate-methyl, flufenacet, thiamethoxam, etc.

[0006] Sulfonate compounds are an important class of active compounds, mainly including sulfonamides and sulfonic acid esters. Most of them have antibacterial, antitumor, herbicidal and insecticidal activities, and are widely studied and applied in medicine and pesticides.

[0007] In summary, the present invention combines the special chemical properties of sulfonate compounds with heterocyclic compounds with biological activity. The sulfonate structure has strong lipophilicity, which can improve the penetration ability and make the small molecule compound more easily exert its efficacy. On this basis, the novel sulfonate compound is compounded with allicin with antibacterial activity to form a compound composition. While testing its antibacterial activity, the plant growth regulator activity is also studied, hoping to screen out highly active antibacterial plant growth regulators. Summary of the invention

[0008] The object of the present invention is to provide a novel sulfonate biological plant growth regulator with bactericidal activity and a preparation method of the composition thereof.

[0009] Another object of the present invention is to provide a novel compound having an inhibitory effect on kiwi fruit bacterial canker, rice bacterial leaf streak pathogen and citrus canker pathogen.

[0010] The technical solution of the present invention is: a novel ferulic acid derivative containing a sulfonamide structure, wherein the derivative has the following general formula (I):

[0011]

[0012] Wherein: R is phenyl, 2-methylphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl, 2-cyanophenyl, 3-cyanophenyl, 4-cyanophenyl, 2,5-difluorophenyl, 2,4-dichlorophenyl, 2,4-dinitrophenyl, 2-fluoro-3 chloro-phenyl, 2-bromo-4-fluorophenyl, 3-nitro-4-chlorophenyl, naphthyl, thiophene, pyridine, ethyl, propyl or a disubstituted group of any combination of the above substituents.

[0013] Preferably: R is phenyl, 2-methylphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl, 2-cyanophenyl, 3-cyanophenyl, 4-cyanophenyl, 2,5-difluorophenyl, 2,4-dichlorophenyl, 2,4-dinitrophenyl, 2-fluoro-3 chloro-phenyl, 2-bromo-4-fluorophenyl, 3-nitro-4-chlorophenyl, naphthyl, thiophene, pyridine, ethyl, propyl or a disubstituted group of any combination of the above substituents.

[0014] A novel ferulic acid derivative containing a sulfonamide structure, the specific compound is as follows:

[0015] Compound C1: 4-(2-(pyridin-3-yl)thiazol-5-yl)phenylbenzenesulfonate;

[0016] Compound C2: (4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl-4-methylbenzenesulfonate;

[0017] Compound C3: 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl-3-methoxybenzenesulfonate;

[0018] Compound C4: 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl-4-methoxybenzenesulfonate;

[0019] Compound C5: 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl-2-fluorobenzenesulfonate;

[0020] Compound C6: 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl-3-fluorobenzenesulfonate;

[0021] Compound C7: 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl-4-fluorobenzenesulfonate;

[0022] Compound C8: 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl-2-chlorobenzenesulfonate;

[0023] Compound C9: 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl-3-chlorobenzenesulfonate;

[0024] Compound C10: 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl-4-chlorobenzenesulfonate;

[0025] Compound C11: 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl-2-bromobenzenesulfonate;

[0026] Compound C12: 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl-3-bromobenzenesulfonate;

[0027] Compound C13: 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl-4-bromobenzenesulfonate;

[0028] Compound C14: 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl-2-nitrobenzenesulfonate;

[0029] Compound C15: 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl-3-nitrobenzenesulfonate;

[0030] Compound C16: 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl-4-nitrobenzenesulfonate;

[0031] Compound C17: 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl-2-cyanobenzenesulfonate;

[0032] Compound C18: 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl-3-cyanobenzenesulfonate;

[0033] Compound C19: 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl-4-cyanobenzenesulfonate;

[0034] Compound C20: 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl 2,6-difluorobenzenesulfonate;

[0035] Compound C21: 4-(2-(Pyridin-3-yl)thiazol-5-yl)phenyl 2,4-dichlorobenzenesulfonate.

[0036] Compound C22: 4-(2-(Pyridin-3-yl)thiazol-5-yl)phenyl 2,4-dinitrobenzenesulfonate.

[0037] Compound C23: 4-(2-(Pyridin-3-yl)thiazol-5-yl)phenyl 3-chloro-2-fluorobenzenesulfonate.

[0038] Compound C24: 4-(2-(Pyridin-3-yl)thiazol-5-yl)phenyl 2-bromo-4-fluorobenzenesulfonate.

[0039] Compound C25: 4-(2-(Pyridin-3-yl)thiazol-5-yl)phenyl-4-chloro-3-nitrobenzenesulfonate.

[0040] Compound C26: 4-(2-(Pyridin-3-yl)thiazol-5-yl)phenylnaphthalene-2-sulfonate.

[0041] Compound C27: 4-(2-(Pyridin-3-yl)thiazol-5-yl)phenylthiophene-2-sulfonate.

[0042] Compound C28: 4-(2-(Pyridin-3-yl)thiazol-5-yl)phenylpyridine-3-sulfonate.

[0043] Compound C29: 4-(2-(Pyridin-3-yl)thiazol-5-yl)phenylethanesulfonate.

[0044] Compound C30: 4-(2-(Pyridin-3-yl)thiazol-5-yl)phenylpropane-1-sulfonate.

[0045] A method for preparing a purine derivative comprises the following steps:

[0046] (1) P 4 S 10 : 3-cyanopyridine = 2:1 feed, 10 mL of ethanol, reflux reaction for 6 hours, after the reaction is completed, wash the mixture with chloroform (150 mL), dry with calcium chloride and concentrate the organic phase. Use ethyl acetate: n-hexane solvent system (v:v = 1:1) to purify the intermediate pyridine-3-carbon sulfamide A by silica gel column chromatography;

[0047]

[0048] (2) Pyridine-3-carbosulfamide A: α-bromo-p-hydroxyacetophenone = 1:1.2, 30 mL of acetonitrile, react at room temperature for 7 h. After the reaction is completed, the solid precipitate is filtered, washed with hot acetonitrile solution, and dried to obtain the key intermediate B;

[0049]

[0050] (3) Add intermediate B: triethylamine: various substituted sulfonyl chlorides in a ratio of 1:3:1.1, add 20 mL of DCM, react at room temperature for 6 h, wash the reaction mixture with saturated brine, then dry the organic phase with anhydrous sodium sulfate and concentrate. The crude product is purified by silica gel column chromatography using a petroleum ether / ethyl acetate solvent system (1:1 v / v) to obtain target compounds C1-C30;

[0051]

[0052] The derivative is used in preparing medicines and medicaments for preventing and controlling rice bacterial leaf streak pathogen, kiwi fruit bacterial canker pathogen and citrus canker pathogen.

[0053] A compound pesticide composition, characterized in that: the composition comprises the novel sulfonate substance according to claim 1 and allicin. The mass ratio of the derivative to Zhongshengmycin is 1:2-2:1. The derivative is C28.

[0054] The composition is used in the preparation of a drug for preventing and treating plant bacterial diseases, wherein the plant bacterial disease is rice bacterial leaf streak pathogen.

[0055] A novel plant growth regulator is compound C28, a compound of the following formula (II):

[0056]

[0057] Beneficial effects of the present invention: From the results of biological activity assay, it can be seen that sulfonate compounds containing thiazole and pyridine structures have moderate to excellent inhibitory activity against bacterial leaf streak pathogen of rice, among which compound C28 has the best activity, with an inhibitory activity of 78.9% against bacterial leaf streak pathogen of rice, which is higher than the control agents thiophanate-copper and thiazole zinc.

[0058] From the results of biological activity determination, it can be seen that the activity of the composite composition against rice bacterial leaf streak pathogen is improved compared with the compound before compounding. The inhibitory activity of composition 3 (C28: allicin wettable powder = 2:1) against rice bacterial leaf streak pathogen is 90.5%. Therefore, the composite composition of C28 and allicin has a synergistic effect on rice bacterial leaf streak pathogen.

[0059] In the wheat germination experiment, some compounds in this series showed good effects in promoting wheat seed germination, especially compounds C4, C5 and C7, which showed better wheat seed germination activity than the control drug DA-6 at 20μg / mL. Overall, among the five concentrations, 20μg / mL had the highest germination rate.

[0060] The cucumber cotyledon expansion test of some target compounds showed that this series of sulfonate compounds containing thiazolylpyridine moiety had certain cytokinin activity, especially compound C27, whose activity was close to that of the control drug thiolone at a concentration of 10 μg / mL. DETAILED DESCRIPTION

[0061] Example:

[0062] 1. The synthesis method of target compounds C1-C30 is as follows. The process firstly involves P 4 S 10 The 3-cyanopyridine was converted into pyridine-3-carbosulfamide (A) by treatment. Subsequently, compound A was directly condensed with α-bromo-p-hydroxyacetophenone in acetonitrile solvent to obtain the key intermediate B (4-(2-(pyridin-3-yl)thiazol-4-yl)phenol). Finally, using triethylamine as an acid-binding agent, intermediate B reacted with various substituted sulfonyl chlorides to undergo nucleophilic substitution reaction to synthesize the target compound.

[0063]

[0064] Preparation of intermediate A:

[0065] P 4 S 10 (8.6 g, 20 mmol) was added to an ethanol (10 mL) solution and stirred at room temperature for 1 h. Subsequently, 3-cyanopyridine (1.0 g, 10 mmol) was added and heated under reflux for 6 hours. After the reaction was completed, the mixture was washed with chloroform (150 mL), dried with calcium chloride and the organic phase was concentrated. Intermediate A was purified by silica gel column chromatography using an ethyl acetate: n-hexane solvent system (v:v = 1:1) with a yield of 78.9%.

[0066] Preparation of intermediate B:

[0067] Pyridine-3-carbosulfamide (0.7 g, 5.0 mmol) and α-bromo-p-hydroxyacetophenone (1.3 g, 6.0 mmol) were added to an acetonitrile (30 mL) solution and stirred at room temperature for 7 h. After the reaction was completed, the solid precipitate was filtered, washed with hot acetonitrile solution, and dried to obtain the key intermediate B with a yield of 85.8%.

[0068] Preparation of target compounds C1-C30:

[0069] Intermediate B (1.2 mmol) was reacted with triethylamine (Et 3 N, 0.49mL, 3.5mmol) was dissolved in DCM (20mL) and stirred at room temperature for 30 minutes. Subsequently, various substituted sulfonyl chlorides (1.4mmol) were added to the solution, and then stirred continuously at room temperature for 6 hours. The reaction mixture was washed with saturated brine, and the organic phase was dried over anhydrous sodium sulfate and concentrated. The crude product was purified by silica gel column chromatography using a petroleum ether / ethyl acetate solvent system (1:1v / v) to obtain the target compounds C1-C30 with a yield of 56.3% to 67.6%.

[0070] 2. Spectral data of target compounds

[0071]

[0072] 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl benzenesulfonate(C1): whitesolid, mp145–146℃, yield: 60.4%. 1 H NMR (400 MHz, DMSO-d 6,ppm)δ:9.20(d,J=2.4Hz,1H),8.69(dd,J=4.7,1.6Hz,1H),8.35(dt,J=8.0,2.0Hz,1H),8.28(s,1H),8.05(d,J=8.5Hz,2H),7.89(d,J=7.8Hz,2H),7.83(t,J=7.5Hz,1H),7.68(t,J=7.7Hz,2H),7.55(dd,J=8.0,4.8Hz,1H),7.13(d,J=8.4Hz,2H); 13 C NMR(100MHz,DMSO-d 6 ,ppm)δ:164.2,154.0,151.1,148.7,147.0,135.1,134.2,133.7,132.9,129.8,128.8,128.3,127.7,124.2,122.5,116.4.HRMS(ESI)m / z:[M+H] + calcd for C 20 H 15 N 2 O 3 S 2 :395.0519,found:395.0500.

[0073]

[0074] 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl 4-methylbenzenesulfonate(C2):white solid,mp 137–140℃,yield:64.3%. 1 H NMR(400MHz,DMSO-d 6 ,ppm)δ:9.20(dd,J=2.3,0.9Hz,1H),8.69(dd,J=4.8,1.6Hz,1H),8.35(ddd,J=8.0,2.4,1.6Hz,1H),8.28(s,1H),8.07–8.03(m,2H),7.77–7.75(m,2H),7.56(ddd,J=7.9,4.8,0.9Hz,1H),7.47(d,J=7.8Hz,2H),7.14–7.10(m,2H),2.41(s,3H); 13 C NMR(100MHz,DMSO-d 6,ppm)δ:164.2,154.0,151.1,148.8,146.9,145.9,133.7,132.8,131.3,130.2,128.8,128.3,127.7,124.3,122.5,116.4,21.2.HRMS(ESI)m / z:[M+Na] + calcd for C 21 H 16 N 2 O 3 S 2 Na:431.0494,found:431.0483.

[0075]

[0076] 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl 3-methoxybenzenesulfonate(C3):white solid,mp 145–146℃,yield:62.3%. 1 H NMR(400MHz,DMSO-d 6 ,ppm)δ:9.20(dd,J=2.4,0.9Hz,1H),8.69(dd,J=4.8,1.6Hz,1H),8.35(ddd,J=8.0,2.4,1.6Hz,1H),8.28(s,1H),8.08–8.05(m,2H),7.60–7.54(m,2H),7.44–7.34(m,3H),7.18–7.15(m,2H),3.83(s,3H); 13 C NMR(100MHz,DMSO-d 6 ,ppm)δ:164.2,159.7,154.0,151.1,148.8,147.0,135.3,133.7,132.9,131.0,128.8,127.7,124.2,122.5,121.2,120.4,116.4,112.6,55.8.HRMS(ESI)m / z:[M+Na] + calcd forC 21 H 16 N 2 O 4 S 2 Na:447.0444,found:447.0434.

[0077]

[0078] 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl 4-methoxybenzenesulfonate(C4):white solid,mp 149–150℃,yield:65.9%. 1 H NMR(400MHz,DMSO-d 6 ,ppm)δ:9.19(dd,J=2.3,0.9Hz,1H),8.68(dd,J=4.8,1.6Hz,1H),8.35(ddd,J=7.9,2.4,1.6Hz,1H),8.27(s,1H),8.07–8.03(m,2H),7.82–7.78(m,2H),7.55(ddd,J=8.0,4.8,0.9Hz,1H),7.18–7.15(m,2H),7.13–7.10(m,2H),3.86(s,3H); 13 C NMR(100MHz,DMSO-d 6 ,ppm)δ:164.2,164.1,154.0,151.0,148.9,146.9,133.7,132.8,130.7,128.8,127.7,125.3,124.2,122.6,116.3,115.0,55.9.HRMS(ESI)m / z:[M+Na] + calcd for C 21 H 16 N 2 O 4 S 2 Na:447.0444,found:447.0432.

[0079]

[0080] 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl 2-fluorobenzenesulfonate(C5):white solid,mp150–152℃,yield:62.6%. 1 H NMR(400MHz,DMSO-d 6,ppm)δ:9.19(dd,J=2.4,0.9Hz,1H),8.68(dd,J=4.8,1.6Hz,1H),8.34(dt,J=8.0,1.9Hz,1H),8.28(s,1H),8.09–8.05(m,2H),7.94–7.88(m,1H),7.81(td,J=7.5,1.8Hz,1H),7.64(ddd,J=10.4,8.4,1.1Hz,1H),7.55(ddd,J=8.0,4.8,0.9Hz,1H),7.44(td,J=7.7,1.1Hz,1H),7.22–7.19(m,2H); 13 C NMR(100MHz,DMSO-d 6 ,ppm)δ:164.2,158.6(d, 1 J C-F =256.0Hz),153.9,151.1,148.5,147.0,138.3(d, 3 J C-F =9.0Hz),133.7,133.2,131.2,128.8,127.9,125.6(d, 4 J C-F =4.0Hz),124.2,122.2,122.1(d, 2 J C-F =13.0Hz),117.9(d, 2 J C-F =20.0Hz),116.6.HRMS(ESI)m / z:[M+Na] + calcd forC 20 H 13 FN 2 O 3 S 2 Na:435.0244,found:435.0234.

[0081]

[0082] 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl 3-fluorobenzenesulfonate(C6):white solid,mp139–141℃,yield:65.5%. 1 H NMR(400MHz,DMSO-d 6,ppm)δ:9.19(d,J=2.1Hz,1H),8.68(dd,J=4.8,1.7Hz,1H),8.34(dt,J=8.0,2.0Hz,1H),8.28(s,1H),8.08–8.05(m,2H),7.80(d,J=8.1Hz,1H),7.76–7.70(m,3H),7.54(ddd,J=8.0,4.8,0.8Hz,1H),7.20–7.16(m,2H); 13 C NMR(100MHz,DMSO-d 6 ,ppm)δ:164.2,161.8(d, 1 J C-F =249.0Hz),153.9,151.1,148.6,147.0,136.0(d, 3 J C-F =7.0Hz),133.6,133.1,132.2(d, 3 J C-F =8.0Hz),128.8,127.8,124.8(d, 4 J C-F =3.0Hz),124.2,122.5,122.4(d, 2 J C-F =21.0Hz),116.5,115.4(d, 2 J C-F =25.0Hz).HRMS(ESI)m / z:[M+Na] + calcd for C 20 H 13 FN 2 O 3 S 2 Na:435.0244,found:435.0235.

[0083]

[0084] 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl 4-fluorobenzenesulfonate(C7):white solid,mp130–131℃,yield:66.9%. 1 H NMR(400MHz,DMSO-d 6,ppm)δ:9.20(dd,J=2.4,0.9Hz,1H),8.69(dd,J=4.8,1.6Hz,1H),8.35(ddd,J=8.0,2.4,1.6Hz,1H),8.29(s,1H),8.08–8.05(m,2H),8.00–7.95(m,2H),7.57–7.50(m,3H),7.16–7.13(m,2H); 13 C NMR(100MHz,DMSO-d 6 ,ppm)δ:165.6(d, 1 J C-F =253.0Hz),164.2,153.9,151.1,148.7,147.0,133.7,133.0,131.7(d, 3 J C-F =10.0Hz),130.4(d, 4 J C-F =3.0Hz),128.8,127.8,124.2,122.6,117.2(d, 2 J C-F =23.0Hz),116.5.HRMS(ESI)m / z:[M+Na] + calcd for C 20 H 13 FN 2 O 3 S 2 Na:435.0244,found:435.0237.

[0085]

[0086] 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl 2-chlorobenzenesulfonate(C8):white solid,mp 139–140℃,yield:59.7%. 1 H NMR(400MHz,DMSO-d 6,ppm)δ:9.19(dd,J=2.4,0.9Hz,1H),8.68(dd,J=4.9,1.6Hz,1H),8.34(dt,J=8.1,1.9Hz,1H),8.27(s,1H),8.08–8.04(m,2H),7.94(dd,J=8.0,1.6Hz,1H),7.89(dd,J=8.0,1.3Hz,1H),7.82(td,J=7.7,1.6Hz,1H),7.58–7.53(m,2H),7.22–7.19(m,2H); 13 C NMR(100MHz,DMSO-d 6 ,ppm)δ:164.2,153.9,151.1,148.5,147.0,136.6,133.7,133.1,132.6,132.4,132.1,131.9,128.8,128.2,127.9,124.2,122.2,116.6.HRMS(ESI)m / z:[M+Na] + calcd forC 20 H 13 ClN 2 O 3 S 2 Na:450.9948,found:450.9940.

[0087]

[0088] 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl 3-chlorobenzenesulfonate(C9):white solid,mp 139–140℃,yield:62.3%. 1 H NMR(400MHz,DMSO-d 6 ,ppm)δ:9.20(dd,J=2.3,0.9Hz,1H),8.68(dd,J=4.8,1.6Hz,1H),8.35(ddd,J=8.0,2.4,1.6Hz,1H),8.29(s,1H),8.09–8.06(m,2H),7.95–7.91(m,2H),7.86(ddd,J=7.9,1.8,1.0Hz,1H),7.71(t,J=8.0Hz,1H),7.55(ddd,J=8.0,4.8,0.9Hz,1H),7.21–7.17(m,2H); 13 C NMR(100MHz,DMSO-d 6,ppm)δ:164.2,153.9,151.1,148.6,147.0,135.9,135.2,134.5,133.7,133.1,131.8,128.8,127.8,127.6,127.1,124.2,122.6,116.6.HRMS(ESI)m / z:[M+Na] + calcd forC 20 H 13 ClN 2 O 3 S 2 Na:450.9948,found:450.9942.

[0089]

[0090] 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl 4-chlorobenzenesulfonate(C10):white solid,mp 154–155℃,yield:67.3%. 1 H NMR(400MHz,DMSO-d 6 ,ppm)δ:9.20(dd,J=2.4,0.9Hz,1H),8.69(dd,J=4.8,1.6Hz,1H),8.36(ddd,J=8.0,2.4,1.7Hz,1H),8.29(s,1H),8.09–8.06(m,2H),7.91–7.88(m,2H),7.77–7.74(m,2H),7.56(ddd,J=8.0,4.8,0.9Hz,1H),7.18–7.14(m,2H); 13 C NMR(100MHz,DMSO-d 6 ,ppm)δ:164.2,153.9,151.1,148.6,147.0,140.2,133.7,133.1,132.9,130.3,130.0,128.8,127.8,124.2,122.6,116.5.HRMS(ESI)m / z:[M+Na] + calcd for C 20 H 13 ClN 2 O 3 S 2 Na:450.9948,found:450.9943.

[0091]

[0092] 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl 2-bromobenzenesulfonate(C11):white solid,mp 151–153℃,yield:60.1%. 1 H NMR(400MHz,DMSO-d 6 ,ppm)δ:9.19(dd,J=2.3,0.8Hz,1H),8.68(dd,J=4.8,1.6Hz,1H),8.35–8.33(m,1H),8.26(s,1H),8.08–8.04(m,3H),7.95(dd,J=7.9,1.7Hz,1H),7.71(td,J=7.7,1.7Hz,1H),7.62–7.53(m,2H),7.23–7.19(m,2H); 13 C NMR(100MHz,DMSO-d 6 ,ppm)δ:164.2,153.9,151.1,148.5,147.0,136.5,136.1,133.9,133.7,133.1,132.6,128.8,128.6,127.9,124.2,122.2,120.4,116.6.HRMS(ESI)m / z:[M+Na] + calcd forC 20 H 13 BrN 2 O 3 S 2 Na:494.9443,found:494.9439.

[0093]

[0094] 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl 3-bromobenzenesulfonate(C12):white solid,mp 150–151℃,yield:62.8%. 1 H NMR(400MHz,DMSO-d 6,ppm)δ:9.20(dd,J=2.3,0.9Hz,1H),8.69(dd,J=4.9,1.6Hz,1H),8.38–8.35(m,1H),8.30(s,1H),8.10–8.05(m,4H),7.90(dt,J=8.0,1.2Hz,1H),7.66–7.62(m,1H),7.56(ddd,J=8.0,4.8,0.9Hz,1H),7.21–7.17(m,2H); 13 C NMR(100MHz,DMSO-d 6 ,ppm)δ:164.2,153.9,151.1,148.6,147.0,138.0,136.0,133.7,133.1,132.0,130.3,128.8,127.8,127.5,124.2,122.6,122.6,116.6.HRMS(ESI)m / z:[M+Na] + calcd forC 20 H 13 BrN 2 O 3 S 2 Na:494.9443,found:494.9440.

[0095]

[0096] 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl 4-bromobenzenesulfonate(C13):white solid,mp 161–162℃,yield:64.8%. 1 H NMR(400MHz,DMSO-d 6 ,ppm)δ:9.20(dd,J=2.3,0.8Hz,1H),8.69(dd,J=4.8,1.6Hz,1H),8.35(dt,J=8.0,2.0Hz,1H),8.29(s,1H),8.09–8.05(m,2H),7.91–7.88(m,2H),7.82–7.79(m,2H),7.55(ddd,J=8.0,4.8,0.9Hz,1H),7.18–7.14(m,2H); 13 C NMR(100MHz,DMSO-d 6,ppm)δ:164.2,153.9,151.1,148.6,147.0,133.7,133.4,133.1,133.0,130.2,129.4,128.8,127.8,124.2,122.6,116.5.HRMS(ESI)m / z:[M+Na] + calcd for C 20 H 13 BrN 2 O 3 S 2 Na:494.9443,found:494.9440.

[0097]

[0098] 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl 2-nitrobenzenesulfonate(C14):yellow solid,mp 160–163℃,yield:63.3%. 1 H NMR(400MHz,DMSO-d 6 ,ppm)δ:9.20(dd,J=2.4,0.9Hz,1H),8.69(dd,J=4.8,1.6Hz,1H),8.36(ddd,J=8.0,2.4,1.7Hz,1H),8.31(s,1H),8.23(dd,J=8.0,1.2Hz,1H),8.13–8.06(m,3H),8.01(dd,J=8.0,1.4Hz,1H),7.89(td,J=7.7,1.2Hz,1H),7.56(ddd,J=8.0,4.8,0.9Hz,1H),7.29–7.26(m,2H); 13 C NMR(100MHz,DMSO-d 6 ,ppm)δ:164.3,153.8,151.1,148.4,148.0,147.0,137.1,133.7,133.4,133.1,131.9,128.8,128.0,125.9,125.4,124.3,122.5,116.7.HRMS(ESI)m / z:[M+Na] + calcd for C 20 H 13 N 3 O 5 S 2 Na:462.0189,found:462.0182.

[0099]

[0100] 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl 3-nitrobenzenesulfonate(C15):yellow solid,mp 142–143℃,yield:61.9%. 1 H NMR(400MHz,DMSO-d 6 ,ppm)δ:9.19(dd,J=2.3,0.9Hz,1H),8.68(dd,J=4.8,1.6Hz,1H),8.65(ddd,J=8.3,2.3,1.0Hz,1H),8.53(t,J=2.1Hz,1H),8.35(ddd,J=8.0,2.4,1.6Hz,1H),8.30(s,1H),8.28(dd,J=1.8,1.0Hz,1H),8.09–8.05(m,2H),7.97(t,J=8.1Hz,1H),7.55(ddd,J=8.0,4.8,0.9Hz,1H),7.24–7.20(m,2H); 13 C NMR(100MHz,DMSO-d 6 ,ppm)δ:164.3,153.8,151.1,148.5,148.2,147.0,135.5,134.2,133.7,133.3,131.9,129.6,128.8,127.9,124.2,123.0,122.7,116.7.HRMS(ESI)m / z:[M+Na] + calcd forC 20 H 13 N 3 O 5 S 2 Na:462.0189,found:462.0177.

[0101]

[0102] 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl 4-nitrobenzenesulfonate(C16):yellow solid,mp 158–161℃,yield:66.3%. 1 H NMR(400MHz,DMSO-d 6,ppm)δ:9.19(d,J=2.4Hz,1H),8.68(dd,J=4.8,1.6Hz,1H),8.47–8.44(m,2H),8.34(dt,J=8.0,2.0Hz,1H),8.30(s,1H),8.19–8.16(m,2H),8.09–8.05(m,2H),7.55(ddd,J=8.0,4.7,0.9Hz,1H),7.21–7.17(m,2H); 13 C NMR(100MHz,DMSO-d 6 ,ppm)δ:164.3,153.8,151.1,148.5,147.0,139.4,133.7,133.2,130.1,128.8,127.9,125.0,124.2,122.6,116.6.HRMS(ESI)m / z:[M+Na] + calcd for C 20 H 13 N 3 O 5 S 2 Na:462.0189,found:462.0182.

[0103]

[0104] 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl 2-cyanobenzenesulfonate(C17):white solid,mp 147–148℃,yield:58.9%. 1 H NMR(400MHz,DMSO-d 6 ,ppm)δ:9.20(dd,J=2.4,0.9Hz,1H),8.69(dd,J=4.8,1.6Hz,1H),8.36(ddd,J=8.0,2.4,1.7Hz,1H),8.32(d,J=1.4Hz,1H),8.31(s,1H),8.11–8.07(m,3H),8.04(td,J=7.6,1.4Hz,1H),7.97(td,J=7.7,1.4Hz,1H),7.56(ddd,J=8.0,4.7,0.9Hz,1H),7.24–7.20(m,2H); 13 C NMR(100MHz,DMSO-d 6,ppm)δ:164.3,153.8,151.1,148.2,147.0,136.6,135.6,135.5,134.3,133.7,133.4,131.1,128.8,128.0,124.3,122.4,116.7,115.2,110.3.HRMS(ESI)m / z:[M+Na] + calcd for C 21 H 13 N 3 O 3 S 2 Na:442.0290,found:442.0276.

[0105]

[0106] 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl 3-cyanobenzenesulfonate(C18):white solid,mp 176–178℃,yield:65.7%. 1 H NMR(400MHz,DMSO-d 6 ,ppm)δ:9.20(d,J=2.2Hz,1H),8.69(dd,J=4.8,1.6Hz,1H),8.48(t,J=1.8Hz,1H),8.36(ddd,J=8.0,2.4,1.6Hz,1H),8.32(t,J=1.3Hz,1H),8.30(s,1H),8.18(ddd,J=8.1,1.9,1.1Hz,1H),8.10–8.06(m,2H),7.87(t,J=7.9Hz,1H),7.56(ddd,J=7.9,4.8,0.9Hz,1H),7.23–7.19(m,2H); 13 C NMR(100MHz,DMSO-d 6 ,ppm)δ:164.3,153.9,151.1,148.5,147.0,138.7,135.4,133.7,133.2,132.7,131.9,131.2,128.8,127.9,124.3,122.6,117.0,116.6,113.3.HRMS(ESI)m / z:[M+Na] + calcd for C 21 H 13 N 3 O 3 S 2Na:442.0290,found:442.0282.

[0107]

[0108] 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl 4-cyanobenzenesulfonate(C19):white solid,mp 141–142℃,yield:64.8%. 1 H NMR(400MHz,DMSO-d 6 ,ppm)δ:9.19(d,J=2.4Hz,1H),8.69(dd,J=4.8,1.6Hz,1H),8.35(dt,J=8.0,2.0Hz,1H),8.29(s,1H),8.17(d,J=8.5Hz,2H),8.10–8.06(m,4H),7.55(dd,J=8.0,4.8Hz,1H),7.19–7.15(m,2H); 13 CNMR(100MHz,DMSO-d 6 ,ppm)δ:164.3,153.9,151.1,148.5,147.0,138.1,133.9,133.7,133.2,129.1,128.8,127.9,124.2,122.6,117.4,117.3,116.6.HRMS(ESI)m / z:[M+Na] + calcd for C 21 H 13 N 3 O 3 S 2 Na:442.0290,found:442.0283.

[0109]

[0110] 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl 2,6-difluorobenzenesulfonate(C20):whitesolid,mp 147–150℃,yield:60.2%. 1 H NMR(400MHz,DMSO-d 6,ppm)δ:9.19(dd,J=2.4,0.9Hz,1H),8.68(dd,J=4.8,1.6Hz,1H),8.35(ddd,J=8.0,2.4,1.6Hz,1H),8.30(s,1H),8.12–8.08(m,2H),7.93(tt,J=8.6,6.1Hz,1H),7.55(ddd,J=7.9,4.8,0.9Hz,1H),7.47–7.41(m,2H),7.28–7.24(m,2H); 13 C NMR(100MHz,DMSO-d 6 ,ppm)δ:164.3,159.1(dd, 1 J C-F =259.0, 3 J C-F =3.0Hz),153.8,151.1,148.3,147.0,138.7(t, 3 J C-F =11.0Hz),133.7,133.4,128.8,128.0,124.2,122.1,116.7,114.0(dt, 2 J C-F =20.0, 4 J C-F =3.0Hz),111.9(t, 2 J C-F =15.0Hz).HRMS(ESI)m / z:[M+Na] + calcd for C 20 H 12 F 2 N 2 O 3 S 2 Na:453.0150,found:453.0136.

[0111]

[0112] 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl 2,4-dichlorobenzenesulfonate(C21):whitesolid,mp 151–152℃,yield:61.8%. 1 H NMR(400MHz,DMSO-d 6,ppm)δ:9.20(dd,J=2.4,0.8Hz,1H),8.69(dd,J=4.8,1.6Hz,1H),8.35(ddd,J=8.0,2.4,1.6Hz,1H),8.29(s,1H),8.13(d,J=2.1Hz,1H),8.10–8.06(m,2H),7.92(d,J=8.5Hz,1H),7.65(dd,J=8.6,2.1Hz,1H),7.56(ddd,J=8.0,4.8,0.9Hz,1H),7.24–7.21(m,2H); 13 C NMR(100MHz,DMSO-d 6 ,ppm)δ:164.3,153.8,151.1,148.4,147.0,140.8,133.7,133.6,133.3,133.2,132.2,131.1,128.8,128.4,128.0,124.2,122.2,116.6.HRMS(ESI)m / z:[M+Na] + calcd forC 20 H 12 Cl 2 N 2 O 3 S 2 Na:484.9559,found:484.9560.

[0113]

[0114] 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl 2,4-dinitrobenzenesulfonate(C22):yellowsolid,mp 149–150℃,yield:56.3%. 1 H NMR(400MHz,DMSO-d 6 ,ppm)δ:9.21(dd,J=2.4,0.9Hz,1H),9.14(d,J=2.3Hz,1H),8.70(dd,J=4.8,1.6Hz,1H),8.62(dd,J=8.7,2.3Hz,1H),8.39–8.35(m,2H),8.28(d,J=8.7Hz,1H),8.15–8.12(m,2H),7.57(ddd,J=7.9,4.8,1.0Hz,1H),7.34–7.30(m,2H); 13 C NMR(100MHz,DMSO-d 6,ppm)δ:164.3,157.8,153.7,151.5,151.1,148.2,147.0,133.7,130.7,128.7,128.2,127.7,127.5,124.3,122.5,121.1,116.9,115.5.HRMS(ESI)m / z:[M+Na] + calcd for C 20 H 12 N 4 O 7 S 2 Na:507.0040,found:507.0035.

[0115]

[0116] 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl 3-chloro-2-fluorobenzenesulfonate(C23):white solid,mp 146–147℃,yield:58.8%. 1 H NMR(400MHz,DMSO-d 6 ,ppm)δ:9.20(d,J=2.3Hz,1H),8.69(dd,J=4.8,1.6Hz,1H),8.36(dt,J=8.0,2.0Hz,1H),8.31(s,1H),8.13–8.08(m,3H),7.79(t,J=6.3Hz,1H),7.56(dd,J=7.9,4.6Hz,1H),7.47(td,J=8.0,1.0Hz,1H),7.27–7.23(m,2H); 13 C NMR(100MHz,DMSO-d 6 ,ppm)δ:164.3,154.1(d, 1 J C-F =257.0),153.8,151.1,148.4,147.0,138.1,133.7,133.3,130.0,128.8,128.0,126.4(d, 3 J C-F =5.0Hz),124.3,123.8(d, 2 J C-F =14.0Hz),122.3,122.2,116.7.HRMS(ESI)m / z:[M+Na] + calcd forC 20 H 12ClFN 2 O 3 S 2 Na:468.9854,found:468.9846.

[0117]

[0118] 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl 2-bromo-4-fluorobenzenesulfonate(C24):white solid,mp 150–151℃,yield:57.9%. 1 H NMR(400MHz,DMSO-d 6 ,ppm)δ:9.20(dd,J=2.4,0.8Hz,1H),8.69(dd,J=4.8,1.6Hz,1H),8.36(dt,J=8.0,2.0Hz,1H),8.29(s,1H),8.12–8.06(m,3H),8.01(dd,J=8.9,5.7Hz,1H),7.56(ddd,J=8.0,4.8,0.9Hz,1H),7.47(ddd,J=8.9,7.9,2.6Hz,1H),7.24–7.20(m,2H); 13 CNMR(100MHz,DMSO-d 6 ,ppm)δ:164.85(d, 1 J C-F =258.0),164.3,153.9,151.1,148.5,147.0,135.2(d, 3 J C-F =10.0Hz),133.7,133.2,130.5(d, 4 J C-F =4.0Hz),128.8,128.0,124.3,123.7(d, 2 J C-F =26.0Hz),122.4(d, 3 J C-F =11.0Hz),122.3,116.6,115.9(d, 2 J C-F =22.0Hz).HRMS(ESI)m / z:[M+Na] + calcd forC 20 H 12 BrFN 2 O 3 S 2Na:512.9349,found:512.9349.

[0119]

[0120] 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl 4-chloro-3-nitrobenzenesulfonate(C25):yellow solid,mp 129–130℃,yield:60.9%. 1 H NMR(400MHz,DMSO-d 6 ,ppm)δ:9.20(dd,J=2.4,0.9Hz,1H),8.69(dd,J=4.8,1.6Hz,1H),8.64(d,J=2.2Hz,1H),8.37(dt,J=8.0,2.0Hz,1H),8.33(s,1H),8.15–8.07(m,4H),7.57(ddd,J=8.0,4.8,0.9Hz,1H),7.28–7.24(m,2H); 13 C NMR(100MHz,DMSO-d 6 ,ppm)δ:164.3,153.9,151.0,148.4,147.9,146.9,134.1,133.7,133.6,133.3,132.9,132.1,128.8,128.0,125.6,124.3,122.7,116.7.HRMS(ESI)m / z:[M+Na] + calcd forC 20 H 12 ClN 3 O 5 S 2 Na:495.9799,found:495.9794.

[0121]

[0122] 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl naphthalene-2-sulfonate(C26):white solid,mp157–160℃,yield:67.6%. 1 H NMR(400MHz,DMSO-d 6,ppm)δ:9.17(dd,J=2.4,0.9Hz,1H),8.67(dd,J=4.8,1.6Hz,1H),8.61(d,J=1.9Hz,1H),8.32(ddd,J=8.0,2.3,1.6Hz,1H),8.24–8.21(m,3H),8.11(d,J=7.1Hz,1H),8.03–8.00(m,2H),7.91(dd,J=8.7,2.0Hz,1H),7.78(t,J=6.9Hz,1H),7.70(t,J=8.2Hz,1H),7.53(ddd,J=8.0,4.8,0.9Hz,1H),7.16–7.13(m,2H); 13 C NMR(100MHz,DMSO-d 6 ,ppm)δ:164.2,153.9,151.0,148.8,146.9,135.1,133.7,132.9,131.5,131.2,130.4,130.0,129.7,128.8,128.1,128.0,127.8,124.2,122.6,116.4.HRMS(ESI)m / z:[M+Na] + calcd for C 24 H 16 N 2 O 3 S 2 Na:467.0494,found:467.0484.

[0123]

[0124] 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl thiophene-2-sulfonate(C27):white solid,mp136–137℃,yield:58.2%. 1 H NMR(400MHz,DMSO-d 6 ,ppm)δ:9.20(d,J=1.6Hz,1H),8.69(dd,J=4.8,1.6Hz,1H),8.35(dt,J=8.0,1.9Hz,1H),8.29(s,1H),8.22(dd,J=5.0,1.4Hz,1H),8.10–8.06(m,2H),7.83(dd,J=3.9,1.4Hz,1H),7.55(dd,J=7.6,5.2Hz,1H),7.29(dd,J=5.0,3.8Hz,1H),7.19–7.15(m,2H);13 CNMR(100MHz,DMSO-d 6 ,ppm)δ:164.2,153.9,151.1,148.8,147.0,137.3,136.7,133.7,133.1,132.8,128.8,128.5,127.8,124.2,122.5,116.5.HRMS(ESI)m / z:[M+Na] + calcd for C 18 H 12 N 2 O 3 S 3 Na:422.9902,found:422.9895.

[0125]

[0126] 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl pyridine-3-sulfonate(C28):white solid,mp120–121℃,yield:60.6%. 1 H NMR(400MHz,DMSO-d 6 ,ppm)δ:9.19(dd,J=2.4,0.9Hz,1H),9.01(dd,J=2.5,0.8Hz,1H),8.98(dd,J=4.9,1.6Hz,1H),8.68(dd,J=4.8,1.6Hz,1H),8.36–8.32(m,2H),8.29(s,1H),8.09–8.05(m,2H),7.74(ddd,J=8.1,4.9,0.9Hz,1H),7.55(ddd,J=8.0,4.8,0.9Hz,1H),7.22–7.18(m,2H); 13 CNMR(100MHz,DMSO-d 6 ,ppm)δ:164.2,155.4,153.9,151.1,148.5,148.3,147.0,136.5,133.7,133.2,131.0,128.8,127.9,124.8,124.2,122.6,116.6.HRMS(ESI)m / z:[M+Na] + calcd forC 19 H 13 N 3 O 3 S 2Na:418.0290,found:418.0287.

[0127]

[0128] 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl ethanesulfonate(C29):whitesolid,mp130–133℃,yield:54.3%. 1 H NMR(400MHz,DMSO-d 6 ,ppm)δ:9.22(dd,J=2.4,0.9Hz,1H),8.70(dd,J=4.8,1.6Hz,1H),8.37(ddd,J=8.0,2.4,1.6Hz,1H),8.32(s,1H),8.17–8.14(m,2H),7.57(ddd,J=8.0,4.8,0.9Hz,1H),7.46–7.43(m,2H),3.57(q,J=7.3Hz,2H),1.40(t,J=7.3Hz,3H); 13 C NMR(100MHz,DMSO-d 6 ,ppm)δ:164.2,154.2,151.1,148.8,147.0,133.7,132.7,128.8,127.9,124.3,122.6,116.3,44.7,8.1.HRMS(ESI)m / z:[M+Na] + calcd for C 16 H 14 N 2 O 3 S 2 Na:369.0338,found:369.0331.

[0129]

[0130] 4-(2-(pyridin-3-yl)thiazol-5-yl)phenyl propane-1-sulfonate(C30):whitesolid,mp169–171℃,yield:61.2%. 1 H NMR(400MHz,DMSO-d 6,ppm)δ:9.22(dd,J=2.4,1.0Hz,1H),8.70(dt,J=4.8,1.4Hz,1H),8.38(dt,J=7.9,1.9Hz,1H),8.33(s,1H),8.18–8.14(m ,2H),7.57(dd,J=7.9,4.8Hz,1H),7.46–7.42(m,2H),3.55(t,J=7.5Hz,2H),1.87(h,J=7.5Hz,2H),1.05(t,J=7.5Hz,3H); 13 C NMR (100 MHz, DMSO-d 6 ,ppm)δ:164.2,154.2,151.1,148.7,147.0,133.7,132.7,128.8,127.9,124.3,122.6,116.3,51.3,17.0,12.4.HRMS(ESI)m / z:[M+Na] + Calculate for C 17 H 16 N 2 O 3 S 2 Na:383.0494,found:383.0487.

[0131] 3. Antimicrobial activity data of target compounds

[0132] The inhibitory activity of the target compounds against bacterial leaf streak of rice, citrus canker, and kiwifruit bacterial canker was evaluated by turbidity. Pure dimethyl sulfoxide (DMSO) was used as a negative control, and zinc thiazole and thiophanate-methyl were used as positive controls. First, prepare NB medium: dissolve the following ingredients: 15g glucose, 7.5g peptone, 1.5g yeast extract, and 4.5g beef extract in 1500ml distilled water. Adjust the pH value to between 7.0 and 7.2. Take 40μL of NB solution containing strains Xoc, Psa or Xac with a pipette and mix it with 4mL NB solution and 1mL 0.1% Tween-20 solution (containing the test compound or positive control agent). Incubate the mixture at 28°C and 180rpm for 1 to 3 days. Optical density was measured at 595nm (OD 595 ) to monitor bacterial growth. When the OD value of the blank control is between 0.6 and 0.8, measure the OD value of the compound. The experiment is set up in triplicate. Turbidity correction value = OD bacterium -OD no bacteria , inhibition rate I=(C tur -T tur ) / Ctur × 100%. Among them, C tur is the turbidity value of the blank control group, T tur is the turbidity value of the compound treatment group, I tur is the inhibition rate.

[0133] Table 1. In vitro antibacterial activity of compounds C1-C30 against Xanthomonas oryzae, Xanthomonas citri var. citri and Xanthomonas avium

[0134]

[0135]

[0136] From the biological activity test results in Table 1, it can be seen that the sulfonate compounds containing thiazole and pyridine structures have moderate to excellent inhibitory activity against rice bacterial leaf streak pathogen, among which compound C28 has the best activity, with an inhibitory activity of 78.9% against rice bacterial leaf streak pathogen, which is higher than the control agents thiophanate-copper and thiazole zinc.

[0137] 4. Preparation of target compound C28 composition

[0138] The wettable powder of the target compound C28 and allicin is used to prepare a composite composition. In each composition, the ratio of the target compound C28 and allicin is calculated according to the mass ratio. The following preparations of the target compound C28 and allicin are prepared as needed.

[0139] Composition 1: C28: Allicin wettable powder = 1:1

[0140] Composition 2: C28: Allicin wettable powder = 1:2

[0141] Composition 3: C28: Allicin wettable powder = 2:1

[0142] Anti-rice bacterial leaf streak activity of the composition of target compound C28

[0143] The antibacterial activity of the combination of target compound C28 and allicin against oxysporum leaf streak of rice was tested according to the turbidity method (the antibacterial activity test method mentioned previously).

[0144] Table 2 Inhibitory activity of drugs against bacterial leaf streak pathogen of rice

[0145]

[0146] The in vitro growth rate method was used to test the activity of the composition against rice bacterial leaf streak pathogen at a concentration of 100 μg / mL. From the biological activity test results in Table 2, it can be seen that the activity of the composite composition against rice bacterial leaf streak pathogen is improved compared with the compounds before compounding. The inhibitory activity of composition 3 (C28: allicin wettable powder = 2:1) against rice bacterial leaf streak pathogen is 90.5%. Therefore, the composite composition of C28 and allicin has a synergistic effect on rice bacterial leaf streak pathogen.

[0147] 5. Plant growth regulating activity

[0148] (1) Wheat seed germination experiment

[0149] First, the target compound to be tested and the control drug DA-6 (aminoethyl ester) were each prepared into a 5% aqueous solution, and then they were diluted with distilled water to a concentration of 10μg / mL, 20μg / mL, 30μg / mL, 60μg / mL and 120μg / mL of plant growth regulator aqueous solution. Subsequently, wheat seeds with rounded appearance and full grains were carefully selected, and these seeds were cultivated with 5% target compound dilution solution, 5% DA-6 dilution solution and clean water for 8 hours. A total of 240 seeds were treated, and each treatment was repeated three times. After the treatment, the seeds were placed one by one in culture dishes of the same size, and double-layer filter paper was laid in the culture dishes, and the number of wheat seeds in each culture dish was ensured to be the same. The wheat seeds were germinated at a constant temperature of 25°C, and the wheat seeds were kept moist during this period. During the seed germination process, carefully observe the germination status of the wheat seeds. When the embryo length is about 0.5cm, take it as the standard. After one day, count the germination rate of all the wheat seeds in the culture dish. After completing the statistical work, calculate the germination promotion rate of each dilution compared with clean water. The specific test data is shown in the following table.

[0150] Table 3. Wheat germination test of some target compounds

[0151]

[0152]

[0153] In the wheat germination experiment, some compounds in this series showed good effects in promoting wheat seed germination, especially compounds C4, C5 and C7, which showed better wheat seed germination activity than the control drug DA-6 at 20μg / mL. Overall, among the five concentrations, 20μg / mL had the highest germination rate.

[0154] (2) Cucumber cotyledon expansion experiment

[0155] First, the cucumber seeds required for the biological activity test were soaked, and then sown in an enamel dish with 0.7% agar and a lid, and placed in a dark environment at 26°C for 72 hours, and then carefully selected cucumber seedlings with relatively uniform cotyledon sizes for use. Sample preparation used the filter paper method in the determination of plant hormone active substances. The test concentrations of the samples were set at 10μg / mL and 1μg / mL, and the solvent was DMF. The specific operation process is as follows: first, the samples were prepared into 100μg / mL and 10μg / mL DMF mother solutions, and then 0.3mL of each of the three mother solutions of different concentrations was taken and evenly dripped on a filter paper with a diameter of 6cm. After the solvent was naturally dried, the filter paper containing the sample was placed in a culture dish of the same size as the filter paper, and 3mL of distilled water and 10 cotyledons were added to each culture dish, thus forming a 10μg / mL and 1μg / mL treatment group. The cucumber seeds treated with distilled water were used as the control group. All the culture dishes were placed at 6°C and 3000 Lux for cultivation. After 72 hours, the fresh weight of the cucumber cotyledons in each culture dish was measured. Each treatment was repeated twice to reduce the error. The relevant results were recorded. After the statistics were completed, the expansion promotion rate of the cotyledons of the cucumber seeds treated with the target compound dilution and thidiazuron was calculated compared with the cotyledons of the cucumber seeds treated with water. The detailed experimental results can be found in the table below.

[0156] Table 4. Cucumber cotyledon expansion test of some target compounds

[0157]

[0158]

[0159] The cucumber cotyledon expansion test of some target compounds showed that this series of sulfonate compounds containing thiazolylpyridine moiety had certain cytokinin activity, especially compound C27, whose activity was close to that of the control drug thiolone at a concentration of 10 μg / mL.

Claims

1. A novel sulfonate substance, characterized in that: The structural formula of the novel sulfonate ester substance is as follows: Wherein, R is phenyl, substituted phenyl, heterocycle, or C2-C3 alkyl.

2. A novel sulfonate substance according to claim 1, characterized in that: The substituted phenyl group is a single or double substitution of methyl, methoxy, halogen, nitro, or cyano, and the heterocycle is thiophene or pyridine.

3. The method for preparing a novel sulfonate substance according to claim 1, characterized in that: The reaction formula is as follows:

4. The method for preparing a novel sulfonate substance according to claim 3, characterized in that: The following steps are included: First, through P4S 10 The 3-cyanopyridine is converted into pyridine-3-carbonylthioamide (A) by treatment; subsequently, compound A is directly condensed with α-bromo-p-hydroxyacetophenone in acetonitrile solvent to obtain the key intermediate B; finally, using triethylamine as an acid-binding agent, intermediate B undergoes a nucleophilic substitution reaction with various substituted sulfonyl chlorides to synthesize the target compound.

5. Use of a novel sulfonate substance as claimed in claim 1 or 2 in the preparation of drugs and medicaments for preventing and controlling bacterial leaf streak pathogen of rice, bacterial canker pathogen of kiwi fruit and bacterial canker pathogen of citrus.

6. A compound pesticide composition, characterized in that: The composition comprises the novel sulfonate substance according to claim 1 and allicin.

7. The composition according to claim 6, characterized in that: The mass ratio of the novel sulfonate substance to allicin is 1:2-2:

1.

8. Use of the composition according to claim 6 in the preparation of a medicament for preventing and treating rice bacterial leaf streak disease.

9. The composition according to claim 6, characterized in that: The derivative is C28.

10. Application of the novel sulfonate substance as claimed in claim 1 or 2 in the preparation of plant growth regulators.

Images