3-heterocycle substituted benzotriazole compound as well as preparation method and application thereof

Abstract

The invention discloses a 3-heterocyclic substituted benzoborazole compound with a structure shown as a formula I, R is selected from H, F, Cl, C1-C3 alkyl or C1-C3 alkoxy, and R1 is selected from # imgabs 0 #, # imgabs 1 #, # imgabs 2 #, # imgabs 3 #, # imgabs 4 #, # imgabs 5 # and # imgabs 6 #; r is selected from H, and R1 is selected from # imgabs7 #. The 3-heterocycle substituted benzene borazole compound disclosed by the invention shows high-efficiency and / or broad-spectrum bactericidal activity. The invention discloses application of the 3-heterocyclic substituted benzotriazole compound in killing pathogenic fungi of crops or preventing and treating plant fungal diseases caused by the pathogenic fungi of the crops. The crop pathogenic bacteria comprise strawberry gray mold bacteria, tomato early blight bacteria, wheat scab bacteria, rhizoctonia solani, valsa mali, colletotrichum gloeosporioides and pyricularia oryzae. # imgabs8 #

Description

Technical Field

[0001] The invention belongs to the field of chemistry and relates to agricultural fungicides, and in particular to 3-heterocyclic substituted benzoborazole compounds and a preparation method thereof and application thereof in sterilization. Background Art

[0002] There have been many reports on 3-indole substituted benzoborazole compounds, which show good biological activity, but their structure is somewhat simple. Therefore, the development of benzoborazole compounds with various active heterocyclic substitutions at the 3rd position has positive significance for the extensiveness of their structure and the study of drug activity. Benzothiophene, piperonyl ring, styrene, and azaindole are all important drug molecular scaffolds. The development of green, efficient, and convenient methods for synthesizing benzoborazole molecules containing various heterocyclic substitutions has positive significance both in the field of pharmaceutical science and organic methodology.

[0003] The inventors consulted relevant materials and found that there are few reports on the above-mentioned 3-heterocyclic substituted benzoborazole compounds. Summary of the invention

[0004] The purpose of the present invention is to provide a series of novel 3-heterocyclic substituted benzoborazole compounds by combining o-formylphenylboronic acid with heterocyclic rings such as benzothiophene, piperonyl (1,2-methylenedioxybenzene), styrene, and azaindole, thereby improving the fungicidal activity against agricultural pathogenic fungi and expanding the fungicidal spectrum.

[0005] The objective of the present invention is achieved through the following technical solutions: The structure of the 3-heterocyclic substituted benzoborazole compound is shown in Formula Ⅰ: ; wherein R is selected from H, F, Cl, C 1 -C 3 Alkyl or C 1 -C 3 Alkoxy, R 1 Selected from (Benzothiophene-3-yl), , (phenylvinyl-β-yl), , , , ; but not including: R is selected from H, R 1 Selected from .

[0006] Preferably, R is selected from H, F, Cl or C 1 -C 3 Alkyl, R 1 Selected from , , , , , ; but does not include: R is selected from F substituted at position 6 or 7, methyl substituted at position 6, R 1 Selected from ; R is selected from H, R 1 Selected from , .

[0007] More preferably, R is selected from H, R 1 Selected from , , ; R is selected from F substituted at positions 4, 5, 6, or 7, Cl substituted at positions 5 or 6, CH substituted at position 5 3 , R 1 Selected from ; R is selected from F substituted at positions 4, 5, 6, or 7, Cl substituted at positions 5 or 6, CH substituted at position 5 3 , R 1 Selected from ; R is selected from F substituted at positions 4, 5, 6, or 7, Cl substituted at positions 5 or 6, CH substituted at position 5 3 , R 1 Selected from ; R is selected from F substituted at 4 or 5, Cl substituted at 5 or 6, R 1 Selected from .

[0008] Most preferably, R is selected from H, R 1 Selected from , , ; R is selected from F substituted at 4, 5, 7, Cl substituted at 5, CH 3 , R 1 Selected from ; R is selected from F substituted at positions 4, 5, 6, or 7, Cl substituted at positions 5 or 6, CH substituted at position 5 3 , R 1 Selected from ; R is selected from F substituted at positions 4, 5, or 7, Cl substituted at positions 5 or 6, CH substituted at position 5 3 , R 1 Selected from ; R is selected from F substituted at 4 or 5, Cl substituted at 5 or 6, R 1 Selected from .

[0009] Another object of the present invention is to provide a method for preparing the 3-heterocyclic substituted benzoborazole compounds. When R 1 Selected from , The synthetic route is as follows: ; Wherein, R is as described above; The method comprises: using 1,2-dichloroethane as a reaction solvent and trifluoroacetic acid as a catalyst, reacting o-formylphenylboronic acid represented by formula III with R 1 H undergoes a Friedel-Crafts reaction to obtain a 3-heterocyclic substituted benzoborazole compound as shown in formula I.

[0010] The R 1 The molar ratio of H to o-formylphenylboronic acid is greater than 1:1, preferably 1.5:1, to ensure complete reaction of o-formylphenylboronic acid.

[0011] The dosage of trifluoroacetic acid and o-formylphenylboronic acid is 0.4:2-0.8:2 mL / mmol, preferably 0.8:2 mL / mmol.

[0012] The temperature of the Friedel-Crafts reaction is 40°C to 60°C.

[0013] When R 1 Selected from The synthetic route is as follows: ; Wherein, R is as described above; The method comprises: using toluene as a reaction solvent, reacting o-formylphenylboronic acid, trans-beta-phenyleneboronic acid and nitrosobenzene shown in formula III to obtain 3-phenylene-substituted phenylborazole compounds.

[0014] The molar ratio of trans-beta styrene boronic acid to o-formylphenyl boronic acid is greater than 1:1, preferably 1.5:1, to ensure complete reaction of o-formylphenyl boronic acid.

[0015] The molar ratio of the nitrosobenzene to the o-formylphenylboric acid is 1:1.1 to 1:1.2.

[0016] The reaction temperature is 110-120°C.

[0017] Specifically, toluene is used as a reaction solvent, o-formylphenylboronic acid, trans-beta-styreneboronic acid and toluene having a structure as shown in Formula III are heated to the reaction temperature and refluxed, and then nitrosobenzene is added in multiple times to react under reflux conditions to obtain 3-styrene-substituted phenylborazole compounds. Nitrosobenzene activates the aldehyde group of o-formylphenylboronic acid and the boric acid of styreneboronic acid to form an imine ion and a borate ester intermediate, driving the formation of a carbon-carbon bond to form an α,β-unsaturated carbonyl compound, and then the ketone and the boric acid of o-formylphenylboronic acid undergo intramolecular dehydration to form a five-membered borazole ring. Since nitrosobenzene has certain oxidizing properties and electrophilicity, by adding nitrosobenzene in batches, side reactions that may be caused by adding all of nitrosobenzene at once (such as self-condensation of aldehydes and excessive oxidation of boric acid) can be avoided, and the heat release rate can also be controlled.

[0018] Preferably, nitrosobenzene is added in 2 to 4 times, and the amount of nitrosobenzene added each time is 1 / 2 to 1 / 4 of the total amount of nitrosobenzene.

[0019] The method comprises: using toluene as a reaction solvent, reacting o-formylphenylboronic acid, trans-beta-phenyleneboronic acid and nitrosobenzene shown in formula III to obtain a 3-phenylene-substituted phenylborazole compound; When R 1 Selected from , , , The synthetic route is as follows: ; Wherein, R is as described above; Includes: H 2 O is a reaction solvent, and the o-formylphenylboronic acid shown in Formula III is 1 H undergoes a Friedel-Crafts reaction to obtain a 3-heterocyclic substituted benzoborazole compound as shown in formula I.

[0020] The R 1 The molar ratio of H to o-formylphenylboronic acid is greater than 1:1. To ensure the complete reaction of o-formylphenylboronic acid and remove the unreacted raw material R after treatment 1 Taking all factors into consideration, the R 1 The molar ratio of H to o-formylphenylboronic acid is preferably 1.1:1.

[0021] The temperature of the Friedel-Crafts reaction is 20-30°C.

[0022] The preparation method of the 3-heterocyclic substituted benzoborazole compounds of the present invention also includes purification of the target compound. There are no special requirements for the purification method, and various purification methods conventionally used by those skilled in the art can be used. For example, extraction with an extractant, drying with a desiccant, and impurities can be removed by column chromatography, recrystallization, and the like.

[0023] The 3-heterocyclic substituted benzoborazole compounds of the present invention exhibit high efficiency and / or broad-spectrum fungicidal activity. Therefore, another object of the present invention is to provide the use of the 3-heterocyclic substituted benzoborazole compounds in killing crop pathogenic fungi or preventing and controlling plant fungal diseases caused by crop pathogenic fungi.

[0024] The crop pathogenic fungi are strawberry gray mold, tomato early blight, wheat fusarium, rice sheath blight, apple rot, cucumber anthracnose and rice blast; preferably strawberry gray mold, rice blast, wheat fusarium, rice sheath blight, apple rot and cucumber anthracnose.

[0025] Another object of the present invention is to provide a benzoborazole compound having the structure shown below for use in killing apple rot bacteria or preventing and controlling apple rot disease: .

[0026] Compared with the prior art, the present invention has the following beneficial effects: The invention uses o-formylphenylboronic acid and various heterocycles or simple molecules as starting materials, and can obtain 3-heterocycle substituted benzoborazole compounds through a simple one-step reaction.

[0027] The 3-heterocyclic substituted benzoborazole compounds of the present invention have good fungicidal activity, show high efficiency and / or broad-spectrum fungicidal activity, and can be applied to crop diseases caused by fungi. DETAILED DESCRIPTION

[0028] The technical solution of the present invention will be described in detail below through embodiments.

[0029] In the following examples, unless otherwise specified, all raw materials used in the examples are commercially available and their purity levels are all analytically pure.

[0030] The room temperature is 25℃.

[0031] Example 1

[0032] A series of benzothiophene-containing benzoborazole compounds were synthesized using substituted or unsubstituted formylphenylboronic acid and benzothiophene as raw materials and 1,2-dichloroethane (DCE) as solvent. The synthetic route is as follows:

[0033] Substituted or unsubstituted o-formylphenylboronic acid (2 mmol) and benzothiophene (3 mmol) as shown in formula III are placed in a 50 mL round-bottom flask, 20 mL 1,2-dichloroethane and 0.8 mL trifluoroacetic acid (TFA) are added, and the reaction is carried out at 40°C. The reaction progress is monitored by TLC until the reaction is completed. After the reaction is completed, ethyl acetate and water are used for extraction, and the organic phases are combined. The organic phases are washed with water and saturated sodium chloride solution in sequence, anhydrous sodium sulfate is added to the organic phase for drying, suction filtration, and the solvent is removed by concentration under reduced pressure. Dry loading is used for silica gel column chromatography, and a petroleum ether / ethyl acetate system (the volume ratio of petroleum ether to ethyl acetate is 30:1 to 20:1) is selected as the eluent to purify and obtain the target compound as shown in formula V.

[0034] Synthesis of benzoborazoles containing piperonyl (1,2-methylenedioxybenzene) A series of benzoborazole compounds containing piperonyl ring were synthesized using substituted or unsubstituted formylphenylboronic acid and piperonyl ring as raw materials and 1,2-dichloroethane as solvent. The synthetic route is as follows:

[0035] Place substituted or unsubstituted o-formylphenylboronic acid (2 mmol) and piperonyl ring (3 mmol) as shown in formula III in a 50 mL round-bottom flask, add 20 mL 1,2-dichloroethane and 0.8 mL trifluoroacetic acid, react at 40°C, monitor the reaction progress by TLC until the reaction is completed; after the reaction is completed, extract with ethyl acetate and water, combine the organic phases, wash the organic phases with water and saturated sodium chloride solution in turn, add anhydrous sodium sulfate to the organic phase for drying, filter, concentrate under reduced pressure to remove the solvent, use dry loading, perform silica gel column chromatography, select petroleum ether / ethyl acetate system (volume ratio of petroleum ether to ethyl acetate is 10:1 to 5:1) as eluent, and purify to obtain the target compound as shown in formula VII.

[0036] A series of styrene-containing benzoborazole compounds were synthesized using substituted or unsubstituted formylphenylboronic acid and trans-beta-styreneboronic acid as raw materials and 1,2-dichloroethane as solvent. The synthetic route is as follows:

[0037] Substituted or unsubstituted o-formylphenylboronic acid (2 mmol) and trans-beta-phenyleneboronic acid (3 mmol) as shown in formula III are placed in a 50 mL round-bottom flask, 20 mL toluene is added, and the temperature is raised to 110°C for reflux reaction. After reaching the reflux temperature, a total of 2.2 mmol of nitrosobenzene is added three times, and the reaction progress is monitored by TLC until the reaction is completed. After the reaction is completed, ethyl acetate and water are used for extraction, and the organic phases are combined. The organic phases are washed with water and saturated sodium chloride solution in sequence, anhydrous sodium sulfate is added to the organic phase for drying, suction filtration, and reduced pressure concentration to remove the solvent. Dry loading is used for silica gel column chromatography, and a petroleum ether / ethyl acetate system (the volume ratio of petroleum ether to ethyl acetate is 15:1 to 10:1) is selected as the eluent to purify and obtain the target compound as shown in formula X.

[0038] The synthetic route is as follows:

[0039] in, Selected from , , , .

[0040] Substituted or unsubstituted o-formylphenylboronic acid (3 mmol) as shown in formula III and azaindole (3.3 mmol) as shown in formula XI are placed in a 50 mL round-bottom flask, 15 mL of deionized water are added, and the reaction is carried out at room temperature. The progress of the reaction is monitored by TLC until the reaction is completed. After the reaction is completed, methanol is added to the system to form a 40-50% methanol aqueous solution, and recrystallized at 20-30° C., and the solid is precipitated, filtered, and recrystallized multiple times (the recrystallization solvent is about 50% methanol aqueous solution, and the recrystallization temperature is 20-30° C.) to purify the target product, and the target compound with a structure as shown in formula XII is purified.

[0041] Table 1. 3-Heterocyclic substituted benzoborazole compounds

[0042] The target compound spectrum data are as follows: Compound I-1a: 3-Benzothiophene-substituted 3-benzoborazole; yellow powder, yield: 11%. 1 H NMR (500 MHz, DMSO- d 6 ) δ 9.5 (s, 1H), 8.0 (d, J = 7.7 Hz, 1H), 7.9 (d, J = 6.7 Hz, 1H), 7.7 (d,J = 7.7 Hz, 1H), 7.6 (s, 1H), 7.4 (dt, J = 22.2, 7.3 Hz, 2H), 7.4 – 7.3 (m, 2H),7.3 (d, J = 7.5 Hz, 1H), 6.6 (s, 1H). 13 C NMR (126 MHz, DMSO- d 6 ) δ 155.9, 140.9,137.9, 136.0, 131.5, 131.2, 128.4, 126.1, 125.1, 124.7, 123.6, 123.1, 123.0,122.7, 78.0.HR-MS(ESI): m / z calcd for C 15 H 11 BO 2 S ([M + H] + ) 267.0646, Found 267.0643. Compound I-2a: 3-benzothiophene substituted 3-(4-fluoro)-benzoborazole; white powder, yield: 12%. 1 H NMR (500MHz, DMSO- d 6 ) δ 9.7 (s, 1H), 8.0 (dd, J = 7.0, 1.7 Hz, 1H), 7.7 (d, J = 7.2 Hz,1H), 7.6 (dd, J = 7.3, 1.8 Hz, 1H), 7.6 (s, 1H), 7.5 (td, J = 7.7, 4.4 Hz, 1H), 7.4 – 7.3 (m, 3H), 6.7 (s, 1H). 13 C NMR (126 MHz, DMSO- d 6 ) δ 158.5, 156.5,140.7, 137.9, 134.3, 131.3, 127.4, 126.9, 125.1, 124.7, 123.7, 122.7, 118.5,118.4, 75.0.HR-MS(ESI): m / z calcd for C 15 H 10 BFO 2 S ([M + H]+ ) 285.0551, Found 285.0550. Compound I-3a: 3-benzothiophene substituted 3-(5-fluoro)-benzoborazole; light yellow powder, yield: 21%. 1 H NMR (500 MHz, DMSO- d 6 ) δ 9.6 (s, 1H), 8.0 (dd, J = 6.7, 2.3 Hz, 1H), 7.9 (dd, J =8.1, 5.8 Hz, 1H), 7.7 (dd, J = 7.8, 1.7 Hz, 1H), 7.6 (d, J = 5.7 Hz, 1H), 7.4 –7.3 (m, 2H), 7.3 – 7.2 (m, 1H), 7.1 (dd, J = 9.3, 2.2 Hz, 1H), 6.6 (d, J = 8.1Hz, 1H). 13 C NMR (126 MHz, DMSO- d 6 ) δ 165.9, 163.9, 158.7 (d, J = 8.6 Hz), 140.9,137.8, 135.4, 133.6 (d, J = 9.0 Hz), 126.5, 125.2, 124.8, 123.7, 122.9, 115.9(d, J = 22.0 Hz), 109.9 (d, J = 22.2 Hz), 77.5 (d, J = 2.9 Hz).HR-MS(ESI): m / zcalcd for C 15 H 10 BFO 2 S ([M + H] + ) 285.0551, Found 285.0554. Compound I-4a: 3-benzothiophene substituted 3-(7-fluoro)-benzoborazole; white powder, yield: 17%. 1 H NMR (500MHz, DMSO- d 6) δ 9.6 (s, 1H), 8.0 – 8.0 (m, 1H), 7.7 – 7.7 (m, 1H), 7.6 (s,1H), 7.5 (td, J = 7.8, 5.3 Hz, 1H), 7.4 (td, J = 6.8, 6.1, 3.4 Hz, 2H), 7.1 (t, J =8.1 Hz, 1H), 7.1 (d, J = 7.5 Hz, 1H), 6.7 (s, 1H). 13 C NMR (126 MHz, DMSO- d 6 ) δ165.0, 163.0, 158.8 (d, J = 8.4 Hz), 140.9, 137.7, 135.3, 134.8 (d, J = 7.3 Hz),126.6, 125.2, 124.8, 123.7, 122.9, 119.3 (d, J = 3.2 Hz), 114.5 (d, J = 22.6 Hz),77.8.HR-MS(ESI): m / z calcd for C 15 H 10 BFO 2 S ([M + H] + ) 285.0551, Found 285.0554. Compound I-5a: 3-benzothiophene substituted 3-(5-chloro)-benzoborazole; light yellow powder, yield: 36%. 1 H NMR (500 MHz, DMSO- d 6 ) δ 9.8 (s, 1H), 7.9 (dd, J = 16.9, 7.9 Hz, 3H), 7.6 (s, 1H),7.5 – 7.4 (m, 2H), 7.4 (dt, J = 23.7, 7.4 Hz, 2H), 6.6 (s, 1H). 13 C NMR (126 MHz, DMSO- d 6 ) δ 158.3, 145.7, 139.7, 139.3, 136.8, 133.0, 128.8, 125.1 (d,J = 6.5Hz), 124.4, 123.1, 123.0, 122.7, 78.1.HR-MS(ESI): m / z calcd for C 15 H 10 BCO 2 S([M + H] + ) 301.0258, Found 301.0260. Compound I-6a: 3-Benzothiophene substituted 3-(5-methyl)-benzoborazole; yellow powder, yield: 8%. 1 H NMR (500 MHz, DMSO- d 6 ) δ 9.4 (s, 1H), 8.0 (d, J = 7.8 Hz, 1H), 7.7 (d, J = 7.5 Hz,1H), 7.6 (d, J = 4.5 Hz, 2H), 7.4 – 7.3 (m, 2H), 7.2 (d, J = 7.6 Hz, 1H), 7.1 (s,1H), 6.6 (s, 1H), 2.3 (s, 3H). 13 C NMR (126 MHz, DMSO- d 6 ) δ 170.9, 156.5, 141.4,140.9, 137.8, 136.1, 131.1, 129.2, 126.2, 125.0 (d, J = 9.2 Hz), 124.7, 123.6,123.2 – 122.8 (m), 77.9, 60.3, 21.9.HR-MS(ESI): m / z calcd for C 16 H 13 BO 2 S ([M +H] + ) 281.0802, Found 281.0800. Compound I-1b: 3-piperazine-substituted 3-benzoborazole; yellow powder, yield: 40%. 1 H NMR (500 MHz, DMSO- d 6 ) δ 9.4 (s, 1H), 7.7 (d, J = 7.2 Hz, 1H), 7.4 (td, J= 7.5, 1.3 Hz, 1H),7.3 (t, J = 7.2 Hz, 1H), 7.1 (d, J = 7.6 Hz, 1H), 6.8 (d, J = 7.9 Hz, 1H), 6.7 (dd, J = 8.1, 1.7 Hz, 1H), 6.7 (s, 1H), 6.1 (s, 1H), 5.9 (d, J = 10.0 Hz, 2H). 13 C NMR (126 MHz, DMSO- d 6 ) δ 157.5, 147.9, 147.4, 135.7, 131.4, 131.1, 127.8, 122.7,120.4, 108.7, 107.0, 101.6, 82.0.HR-MS(ESI): m / z calcd for C 14 H 11 BO 4 ([M + H] + )255.0823, Found 255.0821. Compound I-2b: 3-piperazine-substituted 3-(4-fluoro)-benzoborazole; white powder, yield: 78%. 1 H NMR (500MHz, DMSO- d 6 ) δ 9.6 (s, 1H), 7.7 (d, J = 7.2 Hz, 1H), 7.5 (td, J = 7.7, 4.4 Hz,1H), 7.3 – 7.2 (m, 1H), 6.9 (d, J = 8.0 Hz, 1H), 6.8 (dd, J = 8.0, 1.7 Hz, 1H), 6.7 (s, 1H), 6.3 (s, 1H), 6.0 (d, J = 7.8 Hz, 2H). 13 C NMR (126 MHz, DMSO- d 6 ) δ158.4, 156.4, 147.8, 147.6, 142.3 (d, J = 12.5 Hz), 134.1, 130.9 (d, J= 5.6 Hz),127.2 (d, J = 3.5 Hz), 121.1, 118.2 (d, J = 19.6 Hz), 108.6, 107.5, 101.6,79.7.HR-MS(ESI): m / z calcd for C 14 H 10 BFO 4 ([M + H] + ) 273.0729, Found 273.0722. Compound I-3b: 3-piperazine-substituted 3-(5-fluoro)-benzoborazole; white powder, yield: 37%. 1 H NMR (500MHz, DMSO- d 6 ) δ 9.5 (s, 1H), 7.8 (s, 1H), 7.2 (s, 1H), 7.0 – 6.7 (m, 4H), 6.2– 5.9 (m, 3H). 13 C NMR (126 MHz, DMSO- d 6 ) δ 165.9, 163.9, 160.3 (d, J = 8.2 Hz),148.0, 147.5, 135.1, 133.4 (d, J = 9.0 Hz), 120.3, 115.5 (d, J = 22.0 Hz), 109.6(d, J = 22.0 Hz), 108.7, 107.0, 101.6, 81.5.HR-MS(ESI): m / z calcd for C 14 H 10 BFO 4 ([M + H] + ) 273.0729, Found 273.0735. Compound I-4b: 3-piperazine-substituted 3-(6-fluoro)-benzoborazole; yellow solid, yield: 36%. 1 H NMR (500MHz, DMSO- d 6 ) δ 9.6 (s, 1H), 7.5 (dd, J = 8.3, 2.5 Hz, 1H), 7.3 (td, J= 9.3,8.9, 2.6 Hz, 1H), 7.2 (dd, J = 8.4, 4.6 Hz, 1H), 6.9 (d, J = 8.0 Hz, 1H), 6.8(dd, J = 8.0, 1.7 Hz, 1H), 6.7 (d, J = 1.7 Hz, 1H), 6.1 (s, 1H), 6.0 (dd, J = 9.0,1.1 Hz, 2H). 13 C NMR (126 MHz, DMSO- d 6 ) δ 163.3, 161.4, 153.2, 148.0, 147.5,135.4, 124.8 (d, J = 8.2 Hz), 120.4, 118.9 (d, J = 23.5 Hz), 116.5 (d, J = 20.2Hz), 108.7, 107.1, 101.6, 81.7.HR-MS(ESI): m / z calcd for C 14 H 10 BFO 4 ([M + H] + )273.0729, Found 273.0731. Compound I-5b: 3-piperazine-substituted 3-(7-fluoro)-benzoborazole; brown solid, yield: 80%. 1 H NMR (500MHz, DMSO- d 6 ) δ 9.5 (s, 1H), 7.5 (td, J = 7.8, 5.2 Hz, 1H), 7.1 (t, J = 8.1 Hz,1H), 7.0 (d, J = 7.5 Hz, 1H), 6.9 (d, J = 7.9 Hz, 1H), 6.8 (d, J = 8.5 Hz, 1H), 6.8(s, 1H), 6.1 (s, 1H), 6.0 (d, J = 9.9 Hz, 2H). 13 C NMR (126 MHz, DMSO- d6 ) δ 164.8,162.8, 160.3 (d, J = 8.4 Hz), 148.0, 147.6, 135.0, 134.6 (d, J = 7.3 Hz), 120.6,119.3 (d, J = 3.4 Hz), 114.1 (d, J = 22.6 Hz), 108.7, 107.2, 101.6, 81.8.HR-MS(ESI): m / z calcd for C 14 H 10 BFO 4 ([M + H] + ) 273.0729, Found 273.0725. Compound I-6b: 3-piperazine-substituted 3-(5-chloro)-benzoborazole; white powder, yield: 53%. 1 H NMR (500MHz, DMSO- d 6 ) δ 9.6 (s, 1H), 7.8 (d, J = 7.8 Hz, 1H), 7.4 (d, J = 7.9 Hz, 1H),7.2 (s, 1H), 6.9 (d, J = 7.9 Hz, 1H), 6.8 (d, J = 8.1 Hz, 1H), 6.8 (s, 1H), 6.1(s, 1H), 6.0 (d, J = 10.4 Hz, 2H). 13 C NMR (126 MHz, DMSO- d 6 ) δ 159.6, 148.0,147.5, 136.5, 135.0, 132.9, 128.1, 122.8, 120.3, 108.8, 107.0, 101.6,81.5.HR-MS(ESI): m / z calcd for C 14 H 10 BCO 4 ([M + H] + ) 289.0436, Found 289.0435. Compound I-7b: 3-piperazine-substituted 3-(6-chloro)-benzoborazole; yellow powder, yield: 47%.1 H NMR (500MHz, DMSO- d 6 ) δ 9.6 (s, 1H), 7.8 (d, J = 2.1 Hz, 1H), 7.5 (dd, J = 8.2, 2.1 Hz,1H), 7.2 (d, J = 8.2 Hz, 1H), 6.9 (d, J = 8.0 Hz, 1H), 6.8 (dd, J = 8.0, 1.7 Hz,1H), 6.7 (d, J = 1.7 Hz, 1H), 6.1 (s, 1H), 6.0 (dd, J = 8.9, 1.1 Hz, 2H). 13 C NMR (126 MHz, DMSO- d 6 ) δ 156.0, 148.0, 147.5, 135.1, 132.9, 131.3, 130.6, 124.7,120.5, 108.7, 107.1, 101.6, 81.7.HR-MS(ESI): m / z calcd for C 14 H 10 BCO 4 ([M + H] + )289.0436, Found 289.0439. Compound I-8b: 3-piperazine-substituted 3-(5-methyl)-benzoborazole; white solid, yield: 21%. 1 H NMR (500MHz, DMSO- d 6 ) δ 9.3 (s, 1H), 7.7 (d, J = 7.4 Hz, 1H), 7.2 (d, J = 7.5 Hz, 1H), 6.9 (s, 1H), 6.9 (d, J = 7.9 Hz, 1H), 6.8 (dd, J = 8.0, 1.7 Hz, 1H), 6.7 (s, 1H), 6.0 (s, 1H), 6.0 (d, J = 10.4 Hz, 2H), 2.3 (s, 3H). 13C NMR (126 MHz, DMSO- d 6 ) δ158.1, 147.9, 147.3, 141.2, 135.9, 130.9, 128.8, 123.0, 120.3, 108.7, 107.0,101.5, 81.8, 21.9.HR-MS(ESI): m / z calcd for C 15 H 11 BO 2 S ([M + H] + ) 269.0979,Found 269.0975. Compound I-1c: 3-phenylethylene substituted 3-phenylborazole; brown solid, yield: 10%. 1 H NMR (500 MHz, DMSO- d 6 ) δ 9.4 (d, J = 7.8 Hz, 1H), 7.9 – 7.8 (m, 1H), 7.5 (dd, J = 13.5, 7.3 Hz,3H), 7.4 (d, J = 7.0 Hz, 2H), 7.3 (t, J = 7.4 Hz, 2H), 7.3 – 7.2 (m, 1H), 6.8 (d, J = 15.9 Hz, 1H), 6.3 (dd, J = 15.8, 7.0 Hz, 1H), 5.8 (d, J = 7.0 Hz, 1H). 13 C NMR (126 MHz, DMSO- d 6 ) δ 156.3, 136.7, 131.4, 131.2, 130.8, 130.2, 129.2, 128.3,127.9, 127.1, 122.6, 81.6.HR-MS(ESI): m / z calcd for C 15 H 13 BO 2 ([M + H] + )237.1081, Found 237.1079. Compound I-2c: 3-phenylethylene substituted 3-(4-fluoro)-phenylborazole; brown solid, yield: 23%. 1H NMR (500MHz, DMSO- d 6 ) δ 9.6 (s, 1H), 7.6 (d, J = 7.1 Hz, 1H), 7.5 (qd, J = 7.6, 5.2 Hz,3H), 7.4 – 7.3 (m, 2H), 7.3 – 7.2 (m, 2H), 6.8 (d, J = 15.8 Hz, 1H), 6.3 (dd, J =15.8, 7.0 Hz, 1H), 5.9 (d, J = 7.0 Hz, 1H). 13 C NMR (126 MHz, DMSO- d 6 ) δ 158.6,156.6, 141.3 (d, J = 12.7 Hz), 136.5, 131.6, 130.9 (d, J = 5.5 Hz), 129.2, 128.5,128.2, 127.5, 127.1, 118.1 (d, J = 19.7 Hz), 79.0.HR-MS(ESI): m / z calcd forC 15 H 12 BFO 2 ([M + H] + ) 255.0987, Found 255.0982. Compound I-3c: 3-phenylethylene substituted 3-(5-fluoro)-phenylborazole; brown solid, yield: 15%. 1 H NMR (500MHz, DMSO- d 6 ) δ 9.5 (s, 1H), 7.8 (d, J = 6.1 Hz, 1H), 7.5 (d, J = 6.6 Hz, 2H),7.3 (t, J = 6.7 Hz, 2H), 7.3 (t, J = 9.6 Hz, 3H), 6.8 (d, J = 15.8 Hz, 1H), 6.4(ddd, J = 15.9, 6.7, 2.5 Hz, 1H), 5.8 (d, J= 6.6 Hz, 1H). 13 C NMR (126 MHz, DMSO- d 6 ) δ 165.9, 164.0, 159.2 (d, J = 8.3 Hz), 136.6, 133.5 (d, J = 9.0 Hz), 131.0,129.5, 129.1 (d, J = 7.3 Hz), 128.4, 127.1, 126.7, 116.0 – 115.1 (m), 110.2 –109.4 (m), 81.0.HR-MS(ESI): m / z calcd for C 15 H 12 BFO 2 ([M + H] + ) 255.0987, Found 255.0988. Compound I-4c: 3-phenylethylene substituted 3-(5-chloro)-phenylborazole; brown powder, yield: 13%. 1 H NMR (500MHz, DMSO- d 6 ) δ 9.6 (s, 1H), 7.8 (d, J = 7.8 Hz, 1H), 7.5 (d, J = 7.1 Hz, 3H),7.4 (dd, J = 7.8, 1.8 Hz, 1H), 7.3 (t, J = 7.5 Hz, 2H), 7.3 (t, J = 7.3 Hz, 1H),6.8 (d, J = 15.8 Hz, 1H), 6.4 (dd, J = 15.9, 6.7 Hz, 1H), 5.8 (d, J = 6.7 Hz, 1H). 13 C NMR (126 MHz, DMSO- d 6 ) δ 158.5, 136.6 (d, J = 6.5 Hz), 133.0, 131.0, 129.5,129.2, 128.4, 128.2, 127.1, 122.7, 81.0.HR-MS (ESI): m / z calcd for C15 H 12 BCO 2 ([M + H] + ) 271.0695, Found 271.0696. Compound I-5c: 3-phenylethylene substituted 3-(7-fluoro)-phenylborazole; brown solid, yield: 7%. 1 H NMR (500MHz, DMSO- d 6 ) δ 9.5 (s, 1H), 7.6 (td, J = 7.8, 5.2 Hz, 1H), 7.5 (d, J = 7.6 Hz,2H), 7.3 (t, J = 7.5 Hz, 2H), 7.3 (d, J = 7.3 Hz, 1H), 7.2 (d, J = 7.5 Hz, 1H), 7.1(t, J = 8.2 Hz, 1H), 6.8 (d, J = 15.8 Hz, 1H), 6.3 (dd, J = 15.8, 7.1 Hz, 1H), 5.8(d, J = 7.0 Hz, 1H). 13 C NMR (126 MHz, DMSO- d 6 ) δ 165.0, 163.0, 159.3 (d, J = 8.4Hz), 136.6, 134.6 (d, J = 7.4 Hz), 131.4, 129.4, 129.2, 128.5, 127.1, 119.2,114.3 (d, J = 22.5 Hz), 81.4.HR-MS(ESI): m / z calcd for C 15 H 12 BFO 2 ([M + H] + )255.0987, Found 255.0983. Compound I-6c: 3-phenylethylene substituted 3-(6-chloro)-phenylborazole; brown-red solid, yield: 19%. 1 H NMR (500 MHz, DMSO- d 6) δ 9.6 (s, 1H), 7.8 (s, 1H), 7.5 (d, J = 7.7 Hz, 1H), 7.5 (d, J = 7.1 Hz, 2H), 7.4 (d, J = 8.2 Hz, 1H), 7.3 (t, J = 7.0 Hz, 2H), 7.3 (d, J = 7.2Hz, 1H), 6.8 (d, J = 15.6 Hz, 1H), 6.3 (dd, J = 16.0, 6.7 Hz, 1H), 5.8 (d, J = 7.0Hz, 1H). 13 C NMR (126 MHz, DMSO- d 6 ) δ 154.8, 136.6, 133.0, 131.2 (d, J = 19.0 Hz),130.7, 129.6, 129.2, 128.4, 127.1, 124.7, 81.3.HR-MS(ESI): m / z calcd forC 15 H 12 BCO 2 ([M + H] + ) 271.0695, Found 271.0685. Compound I-7c: 3-phenylethylene substituted 3-(5-methyl)-benzoborazole; brown powder, yield: 8%. 1 H NMR (500MHz, DMSO- d 6 ) δ 9.3 (s, 1H), 7.7 (d, J = 7.8 Hz, 1H), 7.5 (d, J = 7.3 Hz, 2H),7.3 (t, J = 7.5 Hz, 2H), 7.3 (t, J = 7.3 Hz, 1H), 7.2 (d, J = 6.1 Hz, 2H), 6.8 (d, J = 15.8 Hz, 1H), 6.3 (dd, J = 15.8, 7.1 Hz, 1H), 5.7 (d, J= 7.0 Hz, 1H), 2.4 (s,3H). 13 C NMR (126 MHz, DMSO- d 6 ) δ 195.0, 156.9, 141.2, 136.7, 131.1, 130.8,130.3, 129.2, 128.9, 128.3, 127.1, 122.9, 81.4, 21.2.HR-MS(ESI): m / z calcdfor C 16 H 15 BO 2 ([M + H] + ) 251.1238, Found 251.1232. Compound I-1d: 3-(7'-aza)-indole substituted 3-benzoborazole; white powder, yield: 41%. 1 H NMR (500MHz, DMSO- d 6 ) δ 11.6 (s, 1H), 9.3 (d, J = 1.6 Hz, 1H), 8.2 (dd, J = 4.7, 1.6 Hz,1H), 7.8 (d, J = 6.4 Hz, 1H), 7.5 (d, J = 2.5 Hz, 1H), 7.5 – 7.4 (m, 2H), 7.3(dd, J = 8.0, 1.7 Hz, 1H), 7.2 (d, J = 7.3 Hz, 1H), 6.9 (dd, J = 7.9, 4.7 Hz, 1H), 6.4 (s, 1H). 13 C NMR (126 MHz, DMSO- d 6 ) δ 157.0, 149.5, 143.3, 131.3, 130.9,127.8, 127.5, 125.5, 122.8, 118.3, 115.8, 113.8, 77.3.HR-MS(ESI): m / z calcdfor C 14 H 11 BN 2 O 2 ([M + H] + ) 251.0986, Found 251.0988. Compound I-2d: 3-(7'-aza)-indole substituted 3-(4-fluoro)-benzoborazole; white powder, yield: 19 %. 1 HNMR (500 MHz, DMSO- d 6 ) δ 11.7 (s, 1H), 9.5 (s, 1H), 8.2 (dd, J = 4.7, 1.6 Hz,1H), 7.7 (d, J = 7.4 Hz, 1H), 7.5 – 7.4 (m, 2H), 7.2 (ddd, J = 11.2, 8.0, 1.4 Hz,2H), 6.9 (dd, J = 7.9, 4.7 Hz, 1H), 6.6 (s, 1H). 13 C NMR (126 MHz, DMSO- d 6 ) δ158.6, 156.6, 149.3, 143.4, 141.8 (d, J = 12.7 Hz), 135.7, 131.0 (d, J = 5.6 Hz),127.3 – 127.0 (m), 125.6, 118.3 – 118.1 (m), 115.9, 112.4, 74.4.HR-MS(ESI):m / z calcd for C 14 H 10 BFN 2 O 2 ([M + H] + ) 269.0892, Found 269.0895. Compound I-3d: 3-(7'-aza)-indole substituted 3-(5-fluoro)-benzoborazole; white powder, yield: 34%. 1 HNMR (500 MHz, DMSO- d 6 ) δ 11.7 (s, 1H), 9.4 (s, 1H), 8.2 (dd, J = 4.7, 1.6 Hz,1H), 7.9 (dd, J = 8.1, 5.7 Hz, 1H), 7.5 (d, J = 2.5 Hz, 1H), 7.3 (dd, J= 7.9, 1.7Hz, 1H), 7.2 (ddd, J = 10.1, 8.1, 2.3 Hz, 1H), 7.0 (dd, J = 9.3, 2.2 Hz, 1H), 6.9(ddd, J = 7.9, 4.7, 1.2 Hz, 1H), 6.4 (s, 1H). 13 C NMR (126 MHz, DMSO- d 6 ) δ 165.9,164.0, 160.0 (d, J = 8.3 Hz), 149.5, 143.4, 133.2 (d, J = 9.1 Hz), 127.4, 125.7,118.1, 115.9, 115.6 (d, J = 21.8 Hz), 113.1, 109.9, 76.8 (d, J = 3.1 Hz).HR-MS(ESI): m / z calcd for C 14 H 10 BFN 2 O 2 ([M + H] + ) 269.0892, Found 269.0899. Compound I-4d: 3-(7'-aza)-indole substituted 3-(6-fluoro)-benzoborazole; white powder, yield: 54%. 1 HNMR (500 MHz, DMSO- d 6 ) δ 11.7 (s, 1H), 9.4 (s, 1H), 8.2 (dd, J = 4.6, 1.6 Hz,1H), 7.6 – 7.5 (m, 2H), 7.3 – 7.2 (m, 3H), 6.9 (dd, J = 7.9, 4.7 Hz, 1H), 6.4(s, 1H). 13 C NMR (126 MHz, DMSO- d 6 ) δ 163.4, 161.5, 152.7, 149.5, 143.4, 127.4,125.6, 124.9 (d, J = 8.1 Hz), 118.8 (d,J = 23.3 Hz), 118.2, 116.4 (d, J = 20.1Hz), 115.9, 113.5, 77.0.HR-MS(ESI): m / z calcd for C 14 H 10 BFN 2 O 2 ([M + H] + )269.0892, Found 269.0897. Compound I-5d: 3-(7'-aza)-indole substituted 3-(7-fluoro)-benzoborazole; white powder, yield: 46%. 1 HNMR (500 MHz, DMSO- d 6 ) δ 11.7 (s, 1H), 9.4 (s, 1H), 8.2 (dd, J = 4.7, 1.6 Hz,1H), 7.5 (d, J = 2.6 Hz, 1H), 7.5 (td, J = 7.8, 5.3 Hz, 1H), 7.3 (dd, J = 8.0, 1.6Hz, 1H), 7.1 (t, J = 8.1 Hz, 1H), 7.0 (d, J = 7.5 Hz, 1H), 6.9 (dd, J = 7.9, 4.7Hz, 1H), 6.5 (s, 1H). 13 C NMR (126 MHz, DMSO- d 6 ) δ 163.4, 161.5, 152.7, 149.5,143.4, 127.4, 125.6, 124.9 (d, J = 8.3 Hz), 118.8 (d, J = 23.4 Hz), 118.2, 116.4(d, J = 20.2 Hz), 115.9, 113.5, 77.0.HR-MS(ESI): m / z calcd for C 14 H 10 BFN 2 O 2 ([M +H] +) 269.0892, Found 269.0895. Compound I-6d: 3-(7'-aza)-indole substituted 3-(5-chloro)-benzoborazole; white powder, yield: 51%. 1 HNMR(500 MHz, ) δ 11.7 (s, 1H), 9.4 (s, 1H), 8.2 (d, J = 4.7 Hz, 1H), 7.8 (d, J =7.8 Hz, 1H), 7.5 (d, J = 2.6 Hz, 1H), 7.5 (d, J = 7.8 Hz, 1H), 7.3 (d, J = 7.9 Hz,1H), 7.2 (s, 1H), 6.9 (dd, J = 7.9, 4.5 Hz, 1H), 6.4 (s, 1H). 13 C NMR (126 MHz, DMSO- d 6 ) δ 159.3, 149.5, 143.4, 136.5, 132.7, 128.2, 127.4, 125.7, 122.8,118.1, 115.9, 113.0, 76.9.HR-MS(ESI): m / z calcd for C 14 H 10 BCN 2 O 2 ([M + H] + )285.0597, Found 285.0600. Compound I-7d: 3-(7'-aza)-indole substituted 3-(6-chloro)-benzoborazole; white powder, yield: 85%. 1 HNMR (500 MHz, DMSO- d 6 ) δ 11.7 (s, 1H), 9.5 (s, 1H), 8.2 (dd, J = 4.7, 1.6 Hz,1H), 7.8 (d, J = 2.0 Hz, 1H), 7.5 (d, J = 2.5 Hz, 1H), 7.5 (dd, J = 8.1, 2.1 Hz,1H), 7.3 (dd, J= 7.9, 1.6 Hz, 1H), 7.2 (d, J = 8.1 Hz, 1H), 6.9 (dd, J = 7.9, 4.7Hz, 1H), 6.4 (s, 1H). 13 C NMR (126 MHz, DMSO- d 6 ) δ 155.5, 149.5, 143.4, 133.9,132.9, 131.3, 130.4, 127.4, 125.7, 124.8, 118.2, 115.9, 113.2, 77.0.HR-MS(ESI): m / z calcd for C 14 H 10 BCN 2 O 2 ([M + H] + ) 285.0597, Found 285.0597. Compound I-8d: 3-(7'-aza)-indole substituted 3-(4-methoxy)-benzoborazole; white powder, yield: 45%. 1 H NMR (500 MHz, DMSO- d 6 ) δ 11.5 (s, 1H), 9.2 (s, 1H), 8.1 (d, J = 4.7 Hz, 1H),7.4 (dd, J = 12.4, 4.8 Hz, 2H), 7.3 (d, J = 6.2 Hz, 2H), 7.1 (d, J = 7.5 Hz, 1H),6.9 (dd, J = 8.0, 4.7 Hz, 1H), 6.4 (s, 1H), 2.5 (s, 3H). 13 C NMR (126 MHz, DMSO- d 6 ) δ 154.7, 149.2, 143.6, 143.0, 130.1, 127.3, 125.2, 122.7, 118.5, 115.7,113.6, 113.3, 100.3, 75.4, 55.5.HR-MS(ESI): m / z calcd for C 15 H 13 BN 2 O3 ([M + H] + )281.1092, Found 281.1095. Compound I-9d: 3-(7'-aza)-indole substituted 3-(5-methoxy)-benzoborazole; white powder, yield: 12%. 1 H NMR (500 MHz, DMSO- d 6 ) δ 11.7 (s, 1H), 9.1 (s, 1H), 8.2 (dd, J = 4.6, 1.6Hz, 1H), 7.7 (dd, J = 8.2, 1.5 Hz, 1H), 7.5 (d, J = 2.5 Hz, 1H), 7.3 (dd, J = 7.9,1.7 Hz, 1H), 7.0 – 6.9 (m, 2H), 6.7 (d, J = 2.2 Hz, 1H), 6.3 (s, 1H), 2.5 (p, J =1.8 Hz, 3H). 13 C NMR (126 MHz, DMSO- d 6 ) δ 162.4, 159.5, 149.5, 143.3, 132.2,127.5, 125.5, 122.8, 118.3, 115.8, 115.1, 113.8, 107.2, 76.9, 55.6.HR-MS(ESI): m / z calcd for C 15 H 13 BN 2 O 3 ([M + H] + ) 281.1092, Found 281.1101. Compound I-10d: 3-(7'-aza)-indole substituted 3-(6-methyl)-benzoborazole; white powder, yield: 16 %. 1 HNMR (500 MHz, DMSO- d 6 ) δ 11.6 (s, 1H), 9.2 (s, 1H), 8.2 (dd, J = 4.7, 1.7 Hz,1H), 7.6 (s, 1H), 7.5 (d, J= 2.5 Hz, 1H), 7.3 (dq, J = 6.4, 2.5, 2.1 Hz, 2H),7.1 (d, J = 7.8 Hz, 1H), 6.9 (dd, J = 7.9, 4.7 Hz, 1H), 6.4 (s, 1H), 2.4 (s, 3H). 13 C NMR (126 MHz, DMSO- d 6 ) δ 154.3, 149.5, 143.3, 136.7, 132.3, 131.1, 127.5,125.4, 122.5, 118.3, 115.8, 114.0, 77.1, 21.5.HR-MS(ESI): m / z calcd forC 15 H 13 BN 2 O 2 ([M + H] + ) 265.1143, Found 265.1143. Compound I-1e: 3-(4'-aza)-indole substituted 3-benzoborazole; yellow solid, yield: 41%. 1 H NMR (500MHz, DMSO- d 6 ) δ 11.3 (s, 1H), 9.2 (s, 1H), 8.3 (dd, J = 4.5, 1.5 Hz, 1H), 7.9 –7.7 (m, 2H), 7.4 – 7.4 (m, 2H), 7.4 – 7.3 (m, 2H), 7.1 (dd, J = 8.2, 4.6 Hz,1H), 6.6 (s, 1H). 13 C NMR (126 MHz, DMSO- d 6 ) δ 158.0, 144.5, 142.8, 131.1,130.8, 129.5, 127.5, 126.8, 122.7, 119.2, 117.2, 116.2, 75.9, 49.1.HR-MS(ESI): m / z calcd for C 14 H 11 BN 2 O 2 ([M + H] +) 251.0986, Found 251.0989. Compound I-2e: 3-(4'-aza)-indole substituted 3-(4-fluoro)-benzoborazole; yellow solid. 1 H NMR (500MHz, DMSO- d 6 ) δ 11.3 (s, 1H), 9.3 (s, 1H), 8.3 (dd, J = 4.6, 1.5 Hz, 1H), 7.7(dd, J = 8.2, 1.6 Hz, 1H), 7.7 – 7.6 (m, 1H), 7.5 – 7.4 (m, 2H), 7.2 (dd, J =9.9, 8.0 Hz, 1H), 7.1 – 7.1 (m, 1H), 6.6 (s, 1H). Compound I-3e: 3-(4'-aza)-indole substituted 3-(5-chloro)-benzoborazole; light yellow powder. 1 H NMR (500MHz, DMSO- d 6 ) δ 11.3 (s, 1H), 9.4 (s, 1H), 8.3 (d, J = 4.9 Hz, 1H), 7.8 (d, J =7.9 Hz, 2H), 7.4 (dd, J = 31.1, 13.5 Hz, 3H), 7.2 – 7.1 (m, 1H), 6.6 (s, 1H).HR-MS(ESI): m / z calcd for C 14 H 10 BCN 2 O 2 ([M + H] + ) 285.0597, Found 285.0600. Compound I-1f: 3-(5'-aza)-indole substituted 3-(5-chloro)-benzoborazole; light yellow powder. 1 H NMR (500MHz, DMSO- d 6 ) δ 11.6 (s, 1H), 9.5 (s, 1H), 8.2 (s, 1H), 8.1 (d, J = 5.7 Hz,1H), 7.8 (d, J= 7.9 Hz, 1H), 7.5 (s, 1H), 7.5 (dd, J = 7.8, 1.8 Hz, 1H), 7.4 (d, J = 5.7 Hz, 1H), 7.3 (d, J = 1.8 Hz, 1H), 6.5 (s, 1H). Compound I-1g: 3-(6'-aza)-indole substituted 3-benzoborazole; white solid, yield: 15%. 1 H NMR (500MHz, DMSO- d 6 ) δ 11.6 (s, 1H), 9.3 (s, 1H), 8.7 (s, 1H), 7.8 (d, J = 54.3 Hz,2H), 7.6 (s, 1H), 7.4 (s, 2H), 7.1 (s, 1H), 6.8 (s, 1H), 6.4 (s, 1H). 13 C NMR (126 MHz, DMSO- d 6 ) δ 157.0, 137.8, 135.1, 134.4, 131.4, 130.9, 129.2, 127.8,122.8, 114.8, 114.1, 76.7.HR-MS(ESI): m / z calcd for C 14 H 11 BN 2 O 2 ([M + H] + )251.0986, Found 251.0989. Compound I-2g: 3-(6'-aza)-indole substituted 3-(4-fluoro)-benzoborazole; white solid. 1 H NMR (500MHz, DMSO- d 6 ) δ 11.7 (s, 1H), 9.5 (s, 1H), 8.7 (s, 1H), 8.0 (s, 1H), 7.6 (s,2H), 7.5 (s, 1H), 7.2 (s, 1H), 6.9 (s, 1H), 6.6 (s, 1H).HR-MS(ESI): m / z calcdfor C 14 H 10 BFN 2 O 2 ([M + H]+ ) 269.0892, Found 269.0894. Compound I-3g: 3-(6'-aza)-indole substituted 3-(5-chloro)-benzoborazole; white powder. 1 H NMR (500MHz, DMSO- d 6 ) δ 11.7 (s, 1H), 9.4 (s, 1H), 8.7 (s, 1H), 8.0 (d, J = 5.6 Hz,1H), 7.8 (d, J = 7.8 Hz, 1H), 7.7 (s, 1H), 7.5 (d, J = 7.9 Hz, 1H), 7.2 (s, 1H), 6.9 (d, J = 5.5 Hz, 1H), 6.5 (s, 1H).HR-MS(ESI): m / z calcd for C 14 H 10 BCN 2 O 2 ([M +H] + ) 285.0597, Found 285.0597.

[0043] Example 2

[0044] Detection of bactericidal activity of target compounds The strawberry gray mold pathogen ( Botrytis cinerea )、Rhizoctonia solani( Rhizoctonia solani )、Triticum fusarium ( Gibberella zeae )、Pyricularia grisea( Magnaporthe oryzae )、Cucumber Anthracnose( Colletotrichum lagenarium )、Apple rot bacteria( Valsa mali ) and tomato early blight ( Alternaria solani ) Seven common plant pathogenic fungi in agriculture were used as experimental objects. The mycelium growth rate method was used to test the antibacterial activity of the synthesized target compounds. A preliminary screening of the antibacterial activity was carried out, and commercial drugs (myclobutanil, boscalid, and tavaborole) were used as controls.

[0045] Experimental equipment: culture dish (Hefei Xinenyuan Biotechnology Co., Ltd.), high pressure sterilizer (TOMY SX-700), electric constant temperature biochemical incubator (Shanghai Jinghong Experimental Equipment Co., Ltd.), eppendrof pipette, double-sided clean workbench (Suzhou Purification Equipment Co., Ltd.), hole puncher, etc.

[0046] Preparation of experimental materials: Prepare potato dextrose agar (PDA) medium; before the experiment, transfer the seven strains to be tested to potato dextrose agar (PDA) medium, culture them at 25±1 ℃ for 3-10 days, and take a mycelium block with a diameter of 5 mm at the edge of the mycelium for measurement.

[0047] Experimental method: The mycelium growth rate method was used to preliminarily screen the antibacterial activity of 36 target compounds. Experimental group: Weigh 2.5 mg of the target compound to be tested, dissolve it in 0.1 mL of dimethyl sulfoxide (DMSO) to prepare a 25 mg / mL mother solution, and then dissolve it in PDA medium to make a final concentration of 50 μg / mL. The pre-prepared mycelium blocks were inoculated on the PDA medium plate and cultured at 25°C for 2-15 days. The colony diameter was checked and recorded, and the percentage of mycelium growth inhibition by each agent was calculated. Set up drug-free plates and commercial drug (azoxystrobin, boscalid, tavaborole) plate controls. The commercial drug plate control only replaced the target compound with commercial drugs, and the rest of the treatment methods were the same as the experimental group; the drug-free plate control used an equal volume of DMSO to replace the mother solution, and the rest of the treatment methods were the same as the experimental group. Each sample was done in parallel three times. The specific experimental data are shown in Table 2.

[0048] Table 2. Preliminary screening results of the antibacterial activity of the target compounds [inhibition rate η (%)] Compound No. Botrytis cinerea Rhizoctonia solani Gibberella graminearum Rice blast fungus Cucumber Anthracnose Apple rot bacteria Alternaria blight I-1a 84.7 81.8 67.2 100 51.1 100 48.6 I-2a 96.9 67.6 74.2 90.7 82.3 100 63.4 I-3a 96.4 72.4 63.4 88 75.9 98.4 61.3 I-4a 89.4 70.6 72.3 80 93.4 100 75.2 I-5a 91.8 88.6 67.9 100 80.2 100 59.1 I-6a 57.3 67.7 43.3 40.1 10.6 100 23.9 I-1b 76.7 64 43.3 30.1 51.1 100 33.3 I-2b 93.9 66 80.1 56.6 88.9 100 37.3 I-3b 89.4 71.6 75 47.8 54.8 100 41.2 I-4b 82.5 71.2 82.7 49.5 64 100 38.2 I-5b 82.8 62.1 70.2 41 71.7 100 47.5 I-6b 83.6 61.9 68.5 36.1 77 100 62.5 I-7b 89.2 67.9 82.5 90.7 93.4 100 62 I-8b 66.7 78.5 51.2 80.9 48.9 100 34.3 I-1c 90 75 43.8 60.7 81.7 100 62 I-2c 95.6 98.3 79.3 79.5 84.9 100 38.7 I-3c 90 73.9 62.4 67.5 67.2 100 52.5 I-4c 82.2 84.5 38.7 91.5 73.8 100 56.3 I-5c 95.6 83.6 70.7 54.9 63 96.7 48.6 I-6c 75.8 87.3 48.9 63.1 73 100 27.3 I-7c 79.3 80.6 53.5 51.8 36.2 95.3 34.2 I-1d 25.8 32.8 13.6 41.5 18 91.5 12.8 I-2d 40 14.4 15.5 15.1 13.1 94.2 19 I-3d 74.7 45.8 36.5 22.6 13.1 100 12.6 I-4d 47.8 25.1 6.5 35.8 16.4 46.8 0 I-5d 30.4 40.2 41 28.3 6.6 56.6 17.8 I-6d 78.9 75.1 45.2 22.6 19.7 100 17 I-7d 64.2 37 25.4 43.4 16.4 83.1 0 I-8d 45.8 12.1 55.1 18.9 11.5 45.8 14.1 I-9d 54.5 14.2 15.1 24.5 9.8 38.6 0 I-10d 58 32.1 37.8 30.2 16.4 70.1 19.3 I-1e 64.9 2.1 5.6 11.3 3.3 7.1 9.8 I-2e 83.3 / 14.7 / / / / I-1g 68.2 0 0 15.1 6.6 0.8 0 I-2g 60 2.5 0 / / / 3 I-3g 75.6 27.1 0.3 / / / 0 Azoxystrobin 63.8 73.1 68.9 73.8 48.7 64.1 14.7 Boscalid 100 86.6 16.2 14.1 39.7 45.6 52.6 Tavaborole 100 100 100 100 100 100 100 Note: The antibacterial activity test concentration of all compounds was 50 μg / mL; “ / ” means not determined; “0” means no antibacterial activity.

[0049] Table 2 shows the bactericidal test results of the target compounds, from which the following conclusions can be drawn.

[0050] 1. 3-Heterocyclic substituted benzoborazole compounds all showed certain antibacterial activity against common agricultural fungi, with some antibacterial effects reaching 100%, and the inhibitory activity against some fungi was significantly higher than that of commercial pesticides (myclobutanil, boscalid, and tavaborole).

[0051] 2. At the tested concentrations, the inhibition rates of most target compounds against apple rot pathogens were higher than those of myclobutanil and boscalid; the inhibition rates against tomato early blight pathogens were generally lower than those of boscalid and tavaborole; among them, compounds I-4a, I-5a, and I-7b had high inhibitory activity against the seven fungi.

[0052] 3. At the tested concentrations, the target compounds showed good antibacterial activity against strawberry gray mold, rice sheath blight, wheat fusarium, rice blast, cucumber anthracnose and apple rot pathogens, especially compounds I-1a, I-2a, I-4a, I-5a, I-6a, I-1b, I-2b, I-3b, I-4b, I-5b, I-6b, I-7b, I-8b, I-1c, I-2c, I-4c, I-6c, I-3d, I-6d, etc., whose inhibition rate against apple rot pathogens reached 100%, which was better than the control agents myclobutanil and boscalid.

[0053] 4. For benzoborazole compounds containing benzothiophene, piperonyl ring or styrene, the activity of compounds substituted by electron-withdrawing groups such as F and Cl is higher than that of the corresponding unsubstituted compounds, while the activity of compounds substituted by electron-pushing groups such as methyl is lower than that of the corresponding unsubstituted compounds. For example, the activity of compound I-5a (R = 5-Cl)> the activity of compound I-1a (R = H)> the activity of compound I-6a (R = 5-Me), and the inhibition rate of compound I-5a with halogen substitution at the 5th position of benzoborazole against cucumber anthracnose is significantly better than that of compound I-6a with methyl at the 5th position of benzoborazole. The substitution position of F and Cl will also affect the activity. For strawberry gray mold fungus, compounds substituted by F at the 4th or 5th position have higher activity, such as I-2a, I-3a, I-2b, I-2c, and I-3c, which are better than compounds substituted by F and Cl at other positions. For rice blast fungus, the activity of 5-Cl substituted compounds such as compound I-5a is higher than that of 4-F and 5-F substituted compounds. In general, the inhibitory activity of F and Cl substituted compounds against different strains varies depending on the substituted sites.

[0054] 5. Overall, the introduction of benzothiophene, piperonyl, styrene, and azaindole all showed good broad-spectrum fungicidal activity against strawberry gray mold, rice sheath blight, wheat fusarium, rice blast, cucumber anthracnose, and apple rot pathogens, and the inhibition rate was better than that of myclobutanil and boscalid.

[0055] Table 3. EC values ​​of target compounds against Botrytis cinerea 50 Value (μg / mL) Compound No. Toxicity equation R <![CDATA[EC 50 ]]> 95% Confidence Interval I-3a Y=0.8935X+4.8752 0.9965 1.3758 1.1582~1.6343 I-5a Y=0.6399X+5.1533 0.9890 0.5761 0.3726~0.8909 I-2b Y=0.8434X+4.3146 0.9806 6.4962 5.2021~8.1122 I-1c Y=0.8354X+4.9122 0.9881 1.2739 0.9166~1.7706 I-2c Y=1.3473X+3.8108 0.9987 7.6319 7.2017~8.0877 I-3c Y=1.1546X+4.8616 0.9941 1.3178 1.0493~1.6549 I-5c Y=1.0561X+4.6128 0.9800 2.3259 1.6896~3.2020 Boscalid Y=1.0414X+5.0533 0.9998 0.8888 0.8421~0.9381 Table 4. EC values ​​of some target compounds against Rhizoctonia solani 50 Value (μg / mL) Compound No. Toxicity equation R <![CDATA[EC 50 ]]> 95% Confidence Interval I-1c Y=1.7439X+3.2794 0.9853 9.6973 7.4185～12.6761 I-2c Y=0.6238X+4.5304 0.9901 5.6588 4.6097～6.9465 I-3c Y=1.6178X+4.0059 0.9403 4.1165 2.6231～6.4602 I-6c Y=0.7844X+4.0657 0.9893 15.5312 10.9915～21.9460 Boscalid Y=0.8659X+4.8886 0.9913 1.3446 1.0220～1.7691 Tavaborole Y=2.2392X+2.6600 0.9967 11.0919 9.4704～12.9911 Table 5. EC values ​​of some target compounds against Magnaporthe oryzae 50 Value (μg / mL) Compound No. Toxicity equation R <![CDATA[EC 50 ]]> 95% Confidence Interval I-2a Y=0.7358X+4.5608 0.9692 3.9528 2.0855～7.4922 I-3a Y=1.9897X+3.7943 0.9972 4.0362 3.6932～4.4111 I-7b Y=1.2981X+4.0491 0.9950 5.4012 3.7993～7.6786 I-4c Y=1.7428X+3.6405 0.9994 6.0263 5.6094～6.4742 Tavaborole Y=10.8067X+1.7447 0.9367 2.0009 1.2817～3.1237 Table 6. EC values ​​of some target compounds against apple rot pathogens 50 Value (μg / mL) Compound No. Toxicity equation R <![CDATA[EC 50 ]]> 95% Confidence Interval I-2a Y=1.3343X+5.6234 0.9102 0.3411 0.1203～0.9673 I-4a Y=2.9439X+4.0598 0.9500 2.0862 1.4061～3.0954 I-5a Y=3.6599X+5.9926 0.9682 0.5355 0.3794～0.7558 I-2b Y=2.5158X+4.7919 0.9732 1.2098 0.8892～1.6459 I-7b Y=2.5681X+4.3798 0.9843 1.7438 1.4107～2.1556 I-2c Y=2.6025X+4.2962 0.9840 1.8640 1.4858～2.3385 Tavaborole Y=1.5660X+5.5824 0.9714 0.4247 0.2965～0.6084 .

Claims

1. A 3-heterocyclic substituted benzoborazole compound having a structure as shown in Formula I: ;in, R is selected from H, F, Cl, C1-C3 alkyl or C1-C3 alkoxy, R1 is selected from , , , , , , ; but not including: R is selected from H, R1 is selected from .

2. The 3-heterocyclic substituted benzoborazole compound according to claim 1, characterized in that: R is selected from H, F, Cl or C1-C3 alkyl, R1 is selected from , , , , , ; but not including: R is selected from F substituted at position 6 or 7, methyl substituted at position 6, R1 is selected from ; R is selected from H, R1 is selected from , .

3. The 3-heterocyclic substituted benzoborazole compound according to claim 2, characterized in that: R is selected from H, R1 is selected from , , ; R is selected from F substituted at positions 4, 5, 6, and 7, Cl substituted at positions 5 and 6, and CH3 substituted at position 5. R1 is selected from ; R is selected from F substituted at positions 4, 5, 6, and 7, Cl substituted at positions 5 and 6, and CH3 substituted at position 5. R1 is selected from ; R is selected from F substituted at positions 4, 5, 6, and 7, Cl substituted at positions 5 and 6, and CH3 substituted at position 5. R1 is selected from ; R is selected from F substituted at 4 and 5, Cl substituted at 5 and 6, and R1 is selected from .

4. 3-Heterocyclic substituted benzoborazole compounds having a structure as shown in Formula I: ;in, R is selected from H, R1 is selected from , , ; R is selected from F substituted at 4, 5, 7, Cl, CH3 substituted at 5, R1 is selected from ; R is selected from F substituted at positions 4, 5, 6, and 7, Cl substituted at positions 5 and 6, and CH3 substituted at position 5. R1 is selected from ; R is selected from F substituted at positions 4, 5, and 7, Cl substituted at positions 5 and 6, and CH3 substituted at position 5, and R1 is selected from ; R is selected from F substituted at 4 and 5, Cl substituted at 5 and 6, and R1 is selected from .

5. A method for preparing the 3-heterocyclic substituted benzoborazole compound according to any one of claims 1 to 4, characterized in that: When R1 is selected from , The synthetic route is as follows: ； Wherein, R is as described in any one of claims 1 to 4; The method comprises: using 1,2-dichloroethane as a reaction solvent and trifluoroacetic acid as a catalyst, allowing o-formylphenylboronic acid represented by formula III to react with R1H to obtain a 3-heterocyclic substituted phenylborazole compound represented by formula I; When R1 is selected from The synthetic route is as follows: ； Wherein, R is as described in any one of claims 1 to 4; The method comprises: using toluene as a reaction solvent, reacting o-formylphenylboronic acid, trans-beta-phenyleneboronic acid and nitrosobenzene shown in formula III to obtain a 3-phenylene-substituted phenylborazole compound; When R1 is selected from , , , The synthetic route is as follows: ； Wherein, R is as described in any one of claims 1 to 4; The method comprises: using H2O as a reaction solvent, and subjecting o-formylphenylboronic acid shown in formula III to a Friedel-Crafts reaction with R1H to obtain a 3-heterocyclic substituted benzoborazole compound shown in formula I.

6. The method for preparing the 3-heterocyclic substituted benzoborazole compound according to claim 5, characterized in that: When R1 is selected from , The molar ratio of R1H to o-formylphenylboronic acid is greater than 1:1; the amount of trifluoroacetic acid to o-formylphenylboronic acid is 0.4:2-0.8:2 mL / mmol; the temperature of the Friedel-Crafts reaction is 40°C-60°C; When R1 is selected from When the molar ratio of trans-beta styrene boronic acid to o-formylphenyl boronic acid is greater than 1:1; the molar ratio of nitrosobenzene to o-formylphenyl boronic acid is 1:1.1 to 1:1.2; the reaction temperature is 110 to 120°C; When R1 is selected from , , , The molar ratio of R1H to o-formylphenylboronic acid is greater than 1:1; and the temperature of the Friedel-Crafts reaction is 20-30°C.

7. The method for preparing the 3-heterocyclic substituted benzoborazole compound according to claim 6, characterized in that: When R1 is selected from , When the molar ratio of R1H to o-formylphenylboronic acid is 1.5:1; the amount of trifluoroacetic acid to o-formylphenylboronic acid is 0.8:2 mL / mmol; When R1 is selected from When the molar ratio of trans-beta styrene boronic acid to o-formylphenyl boronic acid is 1.5:1; When R1 is selected from , , , When the molar ratio of R1H to o-formylphenylboronic acid is 1.1:

1.

8. Use of the 3-heterocyclic substituted benzoborazole compound according to any one of claims 1 to 4 in killing pathogenic fungi of crops or preventing and controlling plant fungal diseases caused by pathogenic fungi of crops.

9. The use according to claim 8, characterized in that: The crop pathogenic fungi are strawberry gray mold, tomato early blight, wheat fusarium, rice sheath blight, apple rot, cucumber anthracnose and rice blast.

10. Application of benzoborazole compounds having the following structure in killing apple rot pathogens or preventing and controlling apple rot diseases: 。

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