3-Heterocyclic-substituted phenylborazole compounds, their preparation methods and applications

Abstract

The present invention discloses 3-heterocyclic substituted benzeneborazoles with a structure as shown in Formula I, where R is selected from H, F, Cl, C1-C3 alkyl or C1-C3 alkoxy, and R1 is selected from #imgabs0#, #imgabs1#, #imgabs2#, #imgabs3#, #imgabs4#, #imgabs5#, #imgabs6#; provided that it does not include: R is selected from H and R1 is selected from #imgabs7#. The 3-heterocyclic substituted benzeneborazoles described in the present invention exhibit high-efficiency and / or broad-spectrum bactericidal activity. The present invention discloses the application of the 3-heterocyclic substituted benzeneborazoles in killing pathogenic fungi of crops or preventing and controlling plant fungal diseases caused by pathogenic fungi of crops, and the pathogenic fungi of crops are Botrytis cinerea of strawberry, Alternaria solani of tomato, Gibberella zeae of wheat, Rhizoctonia solani of rice, Valsa mali of apple, Colletotrichum orbiculare of cucumber, Magnaporthe oryzae. #imgabs8#

Description

Technical Field

[0001] The present invention belongs to the field of chemistry, relates to agricultural fungicides, and specifically relates to 3-heterocyclic substituted benzeneborazole compounds, their preparation methods and applications in sterilization. Background Art

[0002] There have been many reports on 3-indole substituted benzeneborazole compounds, which show good biological activities, but their structures are somewhat single. Therefore, the development of benzeneborazole compounds substituted with various active heterocycles at the 3-position is of positive significance for both the extensiveness of their structures and the research on drug activities. Benzothiophene, piperonal, styrene, and azaindole are all important drug molecular scaffolds. Developing green, efficient, and convenient methods for synthesizing benzeneborazole molecules substituted with various heterocycles is of positive significance in both 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 benzeneborazole compounds. Summary of the Invention

[0004] The object of the present invention is to provide a series of 3-heterocyclic substituted benzeneborazole compounds with novel structures, improve the bactericidal activity against agricultural pathogenic fungi, and expand the bactericidal spectrum by combining o-formylbenzeneboric acid with heterocycles such as benzothiophene, piperonal (1,2-methylenedioxybenzene), styrene, and azaindole.

[0005] The object of the present invention is achieved through the following technical solutions:[[]]

[0006] 3-heterocyclic substituted benzeneborazole compounds with the structure shown in Formula I:[[]]

[0007] ; wherein, R is selected from H, F, Cl, C1-C3 alkyl or C1-C3 alkoxy, and R1 is selected from (benzothiophen-3-yl), , (styryl-β-yl), , , , ; excluding: when R is selected from H and R1 is selected from .

[0008] Preferably, R is selected from H, F, Cl or C1-C3 alkyl, and R1 is selected from , , , , , ; excluding: when R is selected from F substituted at the 6th or 7th position, methyl substituted at the 6th position, and R1 is selected from ; R is selected from H, and R1 is selected from 、 。

[0009] More preferably, R is selected from H, and R1 is selected from 、 、 ;

[0010] R is selected from F substituted at the 4th, 5th, 6th, or 7th position, Cl substituted at the 5th and 6th positions, CH3 substituted at the 5th position, and R1 is selected from ;

[0011] R is selected from F substituted at the 4th, 5th, 6th, or 7th position, Cl substituted at the 5th and 6th positions, CH3 substituted at the 5th position, and R1 is selected from ;

[0012] R is selected from F substituted at the 4th, 5th, 6th, or 7th position, Cl substituted at the 5th and 6th positions, CH3 substituted at the 5th position, and R1 is selected from ;

[0013] R is selected from F substituted at the 4th and 5th positions, Cl substituted at the 5th and 6th positions, and R1 is selected from 。

[0014] Most preferably, R is selected from H, and R1 is selected from 、 、 ;

[0015] R is selected from F substituted at the 4th, 5th, or 7th position, Cl and CH3 substituted at the 5th position, and R1 is selected from ;

[0016] R is selected from F substituted at the 4th, 5th, 6th, or 7th position, Cl substituted at the 5th and 6th positions, CH3 substituted at the 5th position, and R1 is selected from ;

[0017] R is selected from F substituted at the 4th, 5th, or 7th position, Cl substituted at the 5th and 6th positions, CH3 substituted at the 5th position, and R1 is selected from ;

[0018] R is selected from F substituted at the 4th and 5th positions, Cl substituted at the 5th and 6th positions, and R1 is selected from 。

[0019] Another object of the present invention is to provide a method for preparing the 3-heterocyclic substituted benzoborazoles,

[0020] When R1 is selected from 、 ,the synthesis route is as follows:

[0021] ;

[0022] Among them, R is as described above;

[0023] It includes: using 1,2-dichloroethane as the reaction solvent and trifluoroacetic acid as the catalyst, the o-formylphenylboronic acid shown in formula III undergoes a Friedel-Crafts reaction with R1H to obtain the 3-heterocyclic-substituted benzoborazole compound shown in formula I.

[0024] The molar ratio of the described R1H to o-formylphenylboronic acid > 1:1, preferably 1.5:1, to ensure the complete reaction of o-formylphenylboronic acid.

[0025] The dosage of the described trifluoroacetic acid to o-formylphenylboronic acid is 0.4:2 - 0.8:2 mL / mmol, preferably 0.8:2 mL / mmol.

[0026] The temperature of the described Friedel-Crafts reaction is 40°C - 60°C.

[0027] When R1 is selected from The synthesis route is as follows:

[0028] ;

[0029] Among them, R is as described above;

[0030] It includes: using toluene as the reaction solvent, the o-formylphenylboronic acid, trans-beta-styreneboronic acid, and nitrobenzene shown in formula III react to obtain the 3-styrene-substituted benzoborazole compound.

[0031] The molar ratio of the described trans-beta-styreneboronic acid to o-formylphenylboronic acid > 1:1, preferably 1.5:1, to ensure the complete reaction of o-formylphenylboronic acid.

[0032] The molar ratio of the described nitrobenzene to o-formylphenylboronic acid is 1:1.1 - 1:1.2.

[0033] The temperature of the described reaction is 110 - 120°C.

[0034] Specifically, using toluene as the reaction solvent, o - formylphenylboronic acid, trans - β - styreneboronic acid and toluene with the structure as shown in Formula Ⅲ are heated to the reaction temperature for reflux, and then nitrosobenzene is added in several portions. The reaction is carried out under reflux conditions to obtain 3 - styryl - substituted benzoxazoles. Nitrosobenzene activates the aldehyde group of o - formylphenylboronic acid and the boric acid of styreneboronic acid to form an iminium ion and a borate intermediate, driving the formation of a carbon - carbon bond to form an α,β - unsaturated carbonyl compound. Thereafter, the ketone undergoes intramolecular dehydration with the boric acid of o - formylphenylboronic acid to form a benzoxazole five - membered ring. Since nitrosobenzene has certain oxidizing and electrophilic properties, by adding nitrosobenzene in batches, side reactions that may be caused by adding all nitrosobenzene at once (such as self - condensation of aldehydes and over - oxidation of boric acid) can be avoided, and the exothermic rate can also be controlled.

[0035] Preferably, nitrosobenzene is added in 2 - 4 portions, and the amount of nitrosobenzene added each time is 1 / 2 - 1 / 4 of the total amount of nitrosobenzene.

[0036] It includes: using toluene as the reaction solvent, o - formylphenylboronic acid, trans - β - styreneboronic acid, and nitrosobenzene shown in Formula Ⅲ react to obtain 3 - styryl - substituted benzoxazoles;

[0037] When R1 is selected from 、 、 、 ,the synthesis route is as follows:

[0038] ;

[0039] wherein, R is as described above;

[0040] It includes: using H2O as the reaction solvent, o - formylphenylboronic acid shown in Formula Ⅲ undergoes a Friedel - Crafts reaction with R1H to obtain 3 - heterocyclic - substituted benzoxazoles shown in Formula Ⅰ.

[0041] The molar ratio of the described R1H to o - formylphenylboronic acid > 1:1. Considering comprehensively ensuring the complete reaction of o - formylphenylboronic acid and removing the unreacted raw material R1H in post - treatment, the molar ratio of the described R1H to o - formylphenylboronic acid is preferably 1.1:1.

[0042] The temperature of the described Friedel - Crafts reaction is 20 - 30 °C.

[0043] As the preparation method of the 3 - heterocyclic - substituted benzoxazoles described in the present invention, it also includes the purification of the target compound. There is no special requirement for the purification method, and various purification methods commonly used by those skilled in the art can be adopted. For example, extraction with an extractant, drying with a desiccant, and removing impurities by methods such as column chromatography and recrystallization can be used.

[0044] The 3-heterocyclic substituted benzeneborazole compounds described in the present invention exhibit high-efficiency and / or broad-spectrum bactericidal activities. Therefore, another object of the present invention is to provide the use of the 3-heterocyclic substituted benzeneborazole compounds in killing pathogenic fungi of crops or controlling plant fungal diseases caused by pathogenic fungi of crops.

[0045] The pathogenic fungi of crops are Botrytis cinerea of strawberry, Alternaria solani of tomato, Gibberella zeae of wheat, Rhizoctonia solani of rice, Valsa mali of apple, Colletotrichum orbiculare of cucumber, Magnaporthe oryzae; preferably Botrytis cinerea of strawberry, Magnaporthe oryzae, Gibberella zeae of wheat, Rhizoctonia solani of rice, Valsa mali of apple, Colletotrichum orbiculare of cucumber.

[0046] Another object of the present invention is to provide the use of the benzeneborazole compounds with the following structure in killing Valsa mali of apple or controlling apple canker:

[0047] 。

[0048] Compared with the prior art, the beneficial effects of the present invention:

[0049] In the present invention, o-formylbenzeneboronic acid and various heterocycles or simple molecules are used as starting materials, and 3-heterocyclic substituted benzeneborazole compounds can be obtained through a simple one-step reaction.

[0050] The 3-heterocyclic substituted benzeneborazole compounds of the present invention have good bactericidal activities, exhibit high-efficiency and / or broad-spectrum bactericidal activities, and can be applied to crop diseases caused by fungi. Detailed implementation manners

[0051] The technical solutions of the present invention will be described in detail through the following examples.

[0052] In the following examples, without special instructions, various raw materials used in this example are commercially available, and their purity levels are all analytical pure.

[0053] The room temperature is 25 °C.

[0054] Example 1

[0055] Using substituted or unsubstituted formylbenzeneboronic acid and benzothiophene as raw materials and 1,2-dichloroethane (DCE) as a solvent, a series of benzeneborazole compounds containing benzothiophene are synthesized. The synthesis route is as follows:

[0056]

[0057] Place the substituted or unsubstituted o - formylphenylboronic acid (2 mmol) with the structure as shown in Formula III and benzothiophene (3 mmol) in a 50 mL round - bottom flask, add 20 mL of 1,2 - dichloroethane and 0.8 mL of trifluoroacetic acid (TFA), react at 40 °C, monitor the reaction progress by TLC until the reaction is complete; after the reaction is complete, extract with ethyl acetate and water, combine the organic phases, wash the organic phases successively with water and saturated sodium chloride solution, add anhydrous sodium sulfate to the organic phase for drying, filter by suction, concentrate under reduced pressure to remove the solvent, use dry loading, perform silica gel column chromatography, select the petroleum ether / ethyl acetate system (the volume ratio of petroleum ether to ethyl acetate is 30:1 - 20:1) as the eluent, and purify to obtain the target compound with the structure as shown in Formula V.

[0058] Synthesis of Benzoborazole Compounds Containing Piperonyl (1,2 - Methylenedioxybenzene)

[0059] Using substituted or unsubstituted formylphenylboronic acid and piperonyl as raw materials, and 1,2 - dichloroethane as the solvent, a series of benzoborazole compounds containing piperonyl are synthesized. The synthetic route is as follows:

[0060]

[0061] Place the substituted or unsubstituted o - formylphenylboronic acid (2 mmol) with the structure as shown in Formula III and piperonyl (3 mmol) in a 50 mL round - bottom flask, add 20 mL of 1,2 - dichloroethane and 0.8 mL of trifluoroacetic acid, react at 40 °C, monitor the reaction progress by TLC until the reaction is complete; after the reaction is complete, extract with ethyl acetate and water, combine the organic phases, wash the organic phases successively with water and saturated sodium chloride solution, add anhydrous sodium sulfate to the organic phase for drying. Filter by suction, concentrate under reduced pressure to remove the solvent, use dry loading, perform silica gel column chromatography, select the petroleum ether / ethyl acetate system (the volume ratio of petroleum ether to ethyl acetate is 10:1 - 5:1) as the eluent, and purify to obtain the target compound with the structure as shown in Formula VII.

[0062] Using substituted or unsubstituted formylphenylboronic acid and trans - β - styreneboronic acid as raw materials, and 1,2 - dichloroethane as the solvent, a series of benzoborazole compounds containing styrene are synthesized. The synthetic route is as follows:

[0063]

[0064] Place the substituted or unsubstituted o - formylphenylboronic acid (2 mmol) with the structure as shown in Formula III and trans - β - styreneboronic acid (3 mmol) in a 50 mL round - bottom flask, add 20 mL of toluene, heat to 110 °C for reflux reaction. After reaching the reflux temperature, add a total of 2.2 mmol of nitrosobenzene in three portions, monitor the reaction progress by TLC until the reaction is complete; after the reaction is complete, extract with ethyl acetate and water, combine the organic phases, wash the organic phases successively with water and saturated sodium chloride solution, add anhydrous sodium sulfate to the organic phase for drying, filter by suction, concentrate under reduced pressure to remove the solvent, use dry loading, perform silica gel column chromatography, select the petroleum ether / ethyl acetate system (the volume ratio of petroleum ether to ethyl acetate is 15:1 - 10:1) as the eluent, and purify to obtain the target compound with the structure as shown in Formula X.

[0065] The synthetic route is as follows:

[0066]

[0067] Among them, selected from 、 、 、 。

[0068] Place the substituted or unsubstituted o - formylphenylboronic acid (3 mmol) with the structure as shown in Formula III and the azaindole (3.3 mmol) with the structure as shown in Formula XI in a 50 mL round - bottom flask, add 15 mL of deionized water, react at room temperature, monitor the reaction progress by TLC until the reaction is complete; after the reaction is complete, add methanol to the system to form a 40 - 50% methanol aqueous solution, recrystallize at 20 - 30 °C, wait for the solid to precipitate, filter by suction, and then perform multiple recrystallizations (the solvent for recrystallization is about 50% methanol aqueous solution, and the recrystallization temperature is 20 - 30 °C) to purify and obtain the target product, and purify to obtain the target compound with the structure as shown in Formula XII.

[0069] Table 1. 3 - Heterocyclic - substituted benzoborazoles

[0070]

[0071] The spectral data of the target compound are as follows:

[0072] 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 BO2S ([M + H] + ) 267.0646, Found 267.0643.

[0073] Compound I-2a: 3-Benzothiophene-substituted 3-(4-fluoro)-phenylborazole; 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 BFO2S ([M + H] +) 285.0551, Found 285.0550.

[0074] Compound I-3a: 3-Benzothiophene substituted 3-(5-fluoro)-phenylborazole; pale 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 / z calcd for C 15 H 10 BFO2S ([M + H] + ) 285.0551, Found 285.0554.

[0075] Compound I-4a: 3-Benzothiophene substituted 3-(7-fluoro)-phenylborazole; white powder, yield: 17%. 1 H NMR(500MHz, DMSO- d6) 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 J = 7.8, 5.3 Hz, 1H), 7.4 (td, J J = 6.8, 6.1, 3.4 Hz, 2H), 7.1 (t, J J =8.1 Hz, 1H), 7.1 (d, J J = 7.5 Hz, 1H), 6.7 (s, 1H). 13 13C NMR(126 MHz, DMSO- d d) δ165.0, 163.0, 158.8 (d, J J = 8.4 Hz), 140.9, 137.7, 135.3, 134.8 (d, J J = 7.3 Hz),126.6, 125.2, 124.8, 123.7, 122.9, 119.3 (d, J J = 3.2 Hz), 114.5 (d, J J = 22.6 Hz),77.8.HR-MS(ESI): m / z calcd for C 15 11 10 10 + BFO2S ([M + H]

[0076] Compound I-5a: 3-Benzothiophene substituted 3-(5-chloro)-phenylborazole; pale yellow powder, yield: 36%. 1 1H NMR(500 MHz, DMSO- d d) δ 9.8 (s, 1H), 7.9 (dd, J J = 16.9, 7.9 Hz, 3H), 7.6 (s, 1H),7.5 – 7.4 (m, 2H), 7.4 (dt, J J = 23.7, 7.4 Hz, 2H), 6.6 (s, 1H). 13 13C NMR(126 MHz,DMSO- d d) 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 BClO2S([M + H] + ) 301.0258, Found 301.0260.

[0077] Compound I-6a: 3-benzothiophene-substituted 3-(5-methyl)-phenylborazole; 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 BO2S ([M +H] + ) 281.0802, Found 281.0800.

[0078] Compound I-1b: 3-piperonyl-substituted 3-phenylborazole; 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 BO4([M + H] + )255.0823, Found 255.0821.

[0079] Compound I-2b: 3-(Piperonyl)-3-(4-fluoro)phenylborazole; 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 BFO4([M + H] + ) 273.0729, Found 273.0722.

[0080] Compound I-3b: 3-(Piperonyl)substituted 3-(5-fluoro)phenylborazole; 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 BFO4([M + H] + ) 273.0729, Found 273.0735.

[0081] Compound I-4b: 3-(Piperonyl)substituted 3-(6-fluoro)phenylborazole; 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 = 20.2 Hz), 108.7, 107.1, 101.6, 81.7. HR-MS(ESI): m / z calcd for C 14 H 10 BFO4([M + H] + ) 273.0729, Found 273.0731.

[0082] Compound I-5b: 3-(Piperonyl)-3-(7-fluoro)-benzoxaborole; brown solid, yield: 80%. 1 H NMR(500 MHz, 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- d 6) 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 BFO4([M + H] + ) 273.0729, Found 273.0725.

[0083] Compound I-6b: 3-(Piperonyl)substituted 3-(5-chloro)phenylborazole; 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 BClO4([M + H] + ) 289.0436, Found 289.0435.

[0084] Compound I-7b: 3-(Piperonyl)substituted 3-(6-chloro)phenylborazole; 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 BClO4([M + H] + ) 289.0436, Found 289.0439.

[0085] Compound I-8b: 3-(Piperonyl)-3-(5-methyl)phenylborazole; 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). 13 C 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 BO2S ([M + H]+ ) 269.0979, Found 269.0975.

[0086] Compound I-1c: 3-styryl-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 BO2([M + H] + )237.1081, Found 237.1079.

[0087] Compound I-2c: 3-styryl-substituted 3-(4-fluoro)-phenylborazole; brown solid, yield: 23%. 1 H 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 for C 15 H 12 BFO2([M + H] + ) 255.0987, Found 255.0982.

[0088] Compound I-3c: 3-styryl substituted 3-(5-fluoro)-phenylborazole; brown solid, yield: 15%. 1 H NMR(500 MHz, 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 BFO2([M + H] + ) 255.0987, Found 255.0988.

[0089] Compound I-4c: 3-styryl 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 C 15 H 12 BClO2([M + H] + ) 271.0695, Found 271.0696.

[0090] Compound I-5c: 3-styryl 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 = 8.4 Hz), 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 BFO2([M + H] + ) 255.0987, Found 255.0983.

[0091] Compound I-6c: 3-styryl-substituted 3-(6-chloro)-phenylborazole; brownish 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 = 7.2 Hz, 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 BClO2([M + H] + ) 271.0695, Found 271.0685.

[0092] Compound I-7c: 3-styryl substituted 3-(5-methyl)-phenylborazole; 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 BO2([M + H] + ) 251.1238, Found 251.1232.

[0093] Compound I-1d: 3-(7'-aza)-indole-substituted 3-phenylborazole; 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 BN2O2([M + H] + ) 251.0986, Found 251.0988.

[0094] Compound I-2d: 3-(7'-aza)-indole-substituted 3-(4-fluoro)-phenylborazole; 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 BFN2O2([M + H] + ) 269.0892, Found 269.0895.

[0095] Compound I-3d: 3-(7'-aza)-indole substituted 3-(5-fluoro)-phenylborazole; white powder, yield: 34%. 1 1H NMR(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 BFN2O2([M + H] + ) 269.0892, Found 269.0899.

[0096] Compound I-4d: 3-(7'-aza)-indole-substituted 3-(6-fluoro)-phenylborazole; 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 BFN2O2([M + H] + )269.0892, Found 269.0897.

[0097] Compound I-5d: 3-(7'-aza)-indole-substituted 3-(7-fluoro)-phenylborazole; 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 BFN2O2([M +H] + ) 269.0892, Found 269.0895.

[0098] Compound I-6d: 3-(7'-aza)-indole substituted 3-(5-chloro)-phenylborazole; 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- d6) 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 BClN2O2([M + H] + ) 285.0597, Found 285.0600.

[0099] Compound I-7d: 3-(7'-aza)-indole substituted 3-(6-chloro)-phenylborazole; 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 BClN2O2([M + H] + ) 285.0597, Found 285.0597.

[0100] Compound I-8d: 3-(7'-aza)-indole substituted 3-(4-methoxy)-phenylborazole; 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 BN2O3([M + H] + )281.1092, Found 281.1095.

[0101] Compound I-9d: 3-(7'-azaindolyl) substituted 3-(5-methoxy)phenylborazole; 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- d6) 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 BN2O3([M + H] + ) 281.1092, Found 281.1101.

[0102] Compound I-10d: 3-(7'-aza)-indole substituted 3-(6-methyl)-phenylborazole; white powder, yield: 16%. 1 H NMR(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 for C 15 H 13 BN2O2([M + H] + ) 265.1143, Found 265.1143.

[0103] Compound I-1e: 3-(4'-aza)-indole substituted 3-phenylborazole; yellow solid, yield: 41%. 1 H NMR(500MHz, DMSO- d6) 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 BN2O2([M + H] + ) 251.0986, Found 251.0989.

[0104] Compound I-2e: 3-(4'-aza)-indole-substituted 3-(4-fluoro)-phenylborazole; 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).

[0105] Compound I-3e: 3-(4'-aza)-indole-substituted 3-(5-chloro)-phenylborazole; 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 BClN2O2([M + H] + ) 285.0597, Found 285.0600.

[0106] Compound I-1f: 3-(5'-aza)-indole-substituted 3-(5-chloro)-phenylborazole; pale 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).

[0107] Compound I-1g: 3-(6'-aza)-indole-substituted 3-phenylborazole; 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 BN2O2([M + H] +) 251.0986, Found 251.0989.

[0108] Compound I-2g: 3-(6'-aza)-indole substituted 3-(4-fluoro)-phenylborazole; white solid. 1 H NMR (500 MHz, 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 calcd for C 14 H 10 BFN2O2 ([M + H] + ) 269.0892, Found 269.0894.

[0109] Compound I-3g: 3-(6'-aza)-indole substituted 3-(5-chloro)-phenylborazole; white powder. 1 H NMR (500 MHz, 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 BClN2O2 ([M + H] + ) 285.0597, Found 285.0597。

[0110] Example 2

[0111] Detection of bactericidal activity of the target compound

[0112] Against Botrytis cinerea of strawberry ( Botrytis cinerea ), Rhizoctonia solani of rice ( Rhizoctonia solani ), Gibberella zeae of wheat ( Gibberella zeae ), Magnaporthe oryzae of rice ( Magnaporthe oryzae ), Colletotrichum orbiculare of cucumber (Colletotrichum lagenarium ), Botryosphaeria dothidea ( Valsa mali ), and Alternaria solani ( Alternaria solani ) as experimental objects, the mycelial growth rate method was used to test the antibacterial activity of the synthesized target compounds and conduct a preliminary screening of antibacterial activity, with commercial drugs (azoxystrobin, boscalid, tavaborole) as controls.

[0113] Experimental equipment: Petri dishes (Hefei Xinyuanyuan Biotechnology Co., Ltd.), autoclave (TOMY SX-700), electrothermal constant temperature biochemical incubator (Shanghai Jinghong Experimental Equipment Co., Ltd.), eppendrof pipette, double-sided purification workbench for two people (Suzhou Purification Equipment Co., Ltd.), punchers, etc.

[0114] Preparation of experimental materials: Preparation of potato dextrose agar medium (PDA); before the experiment, the seven test strains were transferred to potato dextrose agar medium (PDA) and cultured at 25 ± 1 °C for 3 - 10 days. Mycelial blocks with a diameter of 5 mm were taken from the edge of the mycelium for determination.

[0115] Experimental method: The mycelial 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 stock solution of 25 mg / mL, and then dissolve it in the PDA medium to make the final concentration 50 μg / mL. The pre-prepared mycelial 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 inhibition of mycelial growth by each agent was calculated. Set a drug-free plate and commercial drug (azoxystrobin, boscalid, tavaborole) plate controls. For the commercial drug plate control, only the commercial drug was used to replace the target compound, and the remaining treatment methods were the same as those of the experimental group; for the drug-free plate control, an equal volume of DMSO was used to replace the stock solution, and the remaining treatment methods were the same as those of the experimental group. Each sample was done in parallel three times. The specific experimental data are shown in Table 2.

[0116] Table 2. Preliminary screening results of antibacterial activity of target compounds [Inhibition rate η(%)]

[0117] Compound number Botrytis cinerea of strawberry Rhizoctonia solani of rice Gibberella zeae of wheat Magnaporthe oryzae Colletotrichum lagenarium of cucumber Valsa mali of apple Alternaria solani of tomato 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

[0118] Note: The test concentration of antibacterial activity of all compounds is 50 μg / mL; " / " indicates not measured; "0" indicates no antibacterial activity.

[0119] Table 2 shows the bactericidal test results of the target compounds, and the following conclusions can be drawn from it.

[0120] 1. 3-Heterocyclic substituted benborazole compounds show certain antibacterial activities against common agricultural fungi. The antibacterial effects of some compounds reach 100%, and the inhibitory activities against some fungi are significantly higher than those of commercial pesticides (azoxystrobin, boscalid, tavaborole).

[0121] 2. At the tested concentrations, the inhibition rates of the vast majority of the target compounds against Valsa mali are higher than those of azoxystrobin and boscalid; the inhibition rates against Alternaria solani are generally lower than those of boscalid and tavaborole; among them, compounds I-4a, I-5a, and I-7b have relatively high inhibitory activities against seven fungi.

[0122] 3. At the tested concentrations, the target compounds show good antibacterial activities against Botrytis cinerea, Rhizoctonia solani, Fusarium graminearum, Magnaporthe oryzae, Colletotrichum orbiculare, and Valsa mali. In particular, the inhibition rates of 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. against Valsa mali reach 100%, which are better than those of the control agents azoxystrobin and boscalid.

[0123] 4. For benborazole compounds containing benzothiophene, piperylene, or styrene, the activities of the compounds substituted by electron-withdrawing groups such as F and Cl are higher than those of the corresponding unsubstituted compounds, while the activities of the compounds substituted by electron-donating groups such as methyl are lower than those 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). The inhibitory rate of compound I-5a with a halogen substitution at the 5th position of benborazole against Colletotrichum orbiculare is significantly better than that of compound I-6a with a methyl group at the 5th position of benborazole. The substitution positions of F and Cl also affect the activity. For Botrytis cinerea, the compounds substituted by F at the 4th or 5th position, such as I-2a, I-3a, I-2b, I-2c, I-3c, have higher activities than those substituted by F and Cl at other positions. For Magnaporthe oryzae, the activity of the 5-Cl substituted compound such as compound I-5a is higher than that of the 4-F and 5-F substituted compounds. Generally speaking, the inhibitory activities of F and Cl substituted compounds against different fungal species vary depending on the substitution sites.

[0124] 5. Generally speaking, the introduction of benzothiophene, piperylene, styrene, and azaindole all show good broad-spectrum bactericidal activities, and show good bactericidal activities against Botrytis cinerea, Rhizoctonia solani, Fusarium graminearum, Magnaporthe oryzae, Colletotrichum orbiculare, and Valsa mali. The inhibition rates are better than those of azoxystrobin and boscalid.

[0125] Table 3. EC of target compounds against Botrytis cinerea of strawberry 50 value (μg / mL)

[0126] Compound number 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

[0127] Table 4. EC of some target compounds against Rhizoctonia solani of rice 50 value (μg / mL)

[0128] Compound number 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

[0129] Table 5. EC of some target compounds against Magnaporthe oryzae 50 value (μg / mL)

[0130] Compound number 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

[0131] Table 6. EC of some target compounds against Valsa mali 50 value (μg / mL)

[0132] Compound number 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. 3-Heterocyclic substituted benzeneborazole compounds with the structure shown in Formula I: ; wherein, R is selected from H, F, Cl or C1-C3 alkyl, and R1 is selected from , , , , , ; Excluding: R is selected from 6- or 7-substituted F, 6-substituted methyl, R1 is selected from ; R is selected from H, R1 is selected from , .

2. The 3-heterocyclic substituted phenylborazole compound according to claim 1, characterized in that: R is selected from H, and R1 is selected from , , ; R is selected from F substituted at the 4-, 5-, 6- or 7-position, Cl substituted at the 5- or 6-position, CH3 substituted at the 5-position, R1 is selected from ; R is selected from F substituted at the 4th, 5th, 6th, or 7th position, Cl substituted at the 5th and 6th positions, CH3 substituted at the 5th position, and R1 is selected from ; R is selected from F substituted at the 4-, 5-, 6- or 7-position, Cl substituted at the 5- and 6-positions, CH3 substituted at the 5-position, R1 is selected from ; R is selected from F substituted at the 4- and 5-positions, Cl substituted at the 5- and 6-positions, and R1 is selected from . 3-Heterocyclic-substituted benzeneborazoles having the structure shown in Formula I: ; wherein, R is selected from H, R1 is selected from , , ; R is selected from F substituted at the 4, 5, or 7 positions, Cl or CH3 substituted at the 5 position, and R1 is selected from ; R is selected from F substituted at the 4, 5, 6, or 7 positions, Cl substituted at the 5 and 6 positions, CH3 substituted at the 5 position, and R1 is selected from ; R is selected from F substituted at the 4, 5, and 7 positions, Cl substituted at the 5 and 6 positions, CH3 substituted at the 5 position, and R1 is selected from ; R is selected from F substituted at the 4- and 5-positions, Cl substituted at the 5- and 6-positions, and R1 is selected from .

4. A method for preparing the 3-heterocyclic substituted benzeneborazole compound according to any one of claims 1-3, characterized in that: When R1 is selected from , the synthesis route is as follows: ； wherein, R is as described in any one of claims 1-3; comprising: using 1,2-dichloroethane as the reaction solvent and trifluoroacetic acid as the catalyst, and carrying out a Friedel-Crafts reaction between o-formylbenzeneboronic acid shown in Formula III and R1H to obtain the 3-heterocyclic substituted benzeneborazole compound shown in Formula I; When R1 is selected from the synthetic route is as follows: ； wherein, R is as described in any one of claims 1-3; comprising: using toluene as the reaction solvent, and carrying out a reaction between o-formylbenzeneboronic acid, trans-beta-styreneboronic acid, and nitrobenzene shown in Formula III to obtain 3-styrene substituted benzeneborazole compounds; When R1 is selected from , , , , the synthesis route is as follows: ； wherein, R is as described in any one of claims 1-3; comprising: using H2O as the reaction solvent, and carrying out a Friedel-Crafts reaction between o-formylbenzeneboronic acid shown in Formula III and R1H to obtain the 3-heterocyclic substituted benzeneborazole compound shown in Formula I.

5. The method for preparing the 3-heterocyclic substituted benzeneborazole compound according to claim 4, characterized in that: When R1 is selected from , , the molar ratio of R1H to o-formylphenylboronic acid > 1:1; the dosages of trifluoroacetic acid and o-formylphenylboronic acid are 0.4:2 to 0.8:2 mL / mmol; the temperature of the Friedel-Crafts reaction is 40°C to 60°C; When R1 is selected from the molar ratio of the trans-beta-styreneboronic acid to the o-formylphenylboronic acid > 1:1; the molar ratio of the nitrobenzene to the o-formylphenylboronic acid is 1:1.1 to 1:1.2; the temperature of the reaction is 110 to 120 °C; When R1 is selected from , , , , the molar ratio of R1H to o - formylphenylboronic acid > 1:1; the temperature of the Friedel - Crafts reaction is 20 - 30 °C.

6. The method for preparing the 3-heterocyclic substituted benzeneborazole compound according to claim 5, characterized in that: When R1 is selected from , , the molar ratio of R1H to 2-formylphenylboronic acid is 1.5:1; the dosage of trifluoroacetic acid and 2-formylphenylboronic acid is 0.8:2 mL / mmol; When R1 is selected from the molar ratio of the trans-beta-styreneboronic acid to o-formylphenylboronic acid is 1.5:1; When R1 is selected from , , , , the molar ratio of R1H to o - formylphenylboronic acid is 1.1:

1.

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

8. The application according to claim 7, wherein The pathogenic fungi of crops are Botrytis cinerea of strawberry, Alternaria solani of tomato, Gibberella zeae of wheat, Rhizoctonia solani of rice, Valsa mali of apple, Colletotrichum orbiculare of cucumber, Magnaporthe oryzae.

9. Use of the benzeneborazole compound with the following structure in killing Valsa mali of apple or preventing and controlling apple canker: 。

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