Phenylpropenamide derivatives, processes for their preparation and uses thereof

Abstract

The application discloses a kind of phenylacrylamide derivatives and preparation method and purposes thereof, belong to organic synthesis chemistry and pesticide technical field.Phenylacrylamide derivatives are prepared by condensation reaction from cinnamic acid or its derivatives and benzimidazole derivatives.Biological activity test shows that the compounds exhibit different degrees of inhibitory activity on rice sheath blight pathogen, barley root rot pathogen, wheat scab pathogen and brassica rapa sclerotinia pathogen, and can be used for preparing fungicide for preventing and treating agricultural plant diseases.

Description

Technical Field

[0001] This invention belongs to the fields of organic synthetic chemistry and pesticide technology, specifically relating to a class of phenylacrylamide derivatives and their preparation methods and uses. Background Technology

[0002] Plant pathogenic fungi can cause a variety of crop diseases, seriously affecting crop yield and quality. Currently, chemical fungicides remain an important means of controlling plant fungal diseases. However, long-term use of a single type of fungicide can easily lead to increased drug resistance in pathogens. Furthermore, some existing fungicides have limitations in their control spectrum and environmental compatibility. Therefore, developing novel fungicide lead compounds with novel structures and high activity is of great significance.

[0003] Cinnamic acid and its derivatives are widely found in natural products, possessing good biological activity and numerous modifiable sites, making them a promising backbone for pesticide active molecule design. The cinnamic acid backbone contains α,β-unsaturated carbonyl groups, facilitating diverse structural modifications. Amide structures are common active linker units in pharmaceutical and pesticide molecules, with amide compounds having been studied and reported for their applications in fungicides, insecticides, and herbicides. In particular, pesticide molecules containing amide structures have achieved good application results, indicating that this type of structure has significant development value in pesticide creation.

[0004] However, existing cinnamic acid derivatives and amide compounds still have limitations in controlling plant pathogenic fungi, including insufficient activity, broad spectrum of activity, and the need to expand their structural types. Therefore, it is necessary to further modify the structure of the cinnamic acid skeleton, construct new phenylacrylamide derivatives using an active substructure splicing strategy, and investigate their preparation methods and fungicidal activity, with the aim of discovering promising new agricultural fungicide lead compounds. Summary of the Invention

[0005] 1. Purpose of the invention The purpose of this invention is to provide a class of phenylacrylamide derivatives, their preparation methods, and uses.

[0006] 2. Technical Solution To achieve the objective of this invention, the technical solution adopted by this invention is as follows: The first aspect of this invention provides a class of phenylacrylamide derivatives, the general structural formula of which is shown in Formula I below: , Wherein, R1 is selected from phenyl or phenyl mono- or di-substituted by fluorine, chlorine, bromine, methyl, methoxy, nitro or hydroxyl; R2 is selected from hydrogen or methyl; R3 is selected from hydrogen or methyl; R4 is selected from hydrogen, chlorine, methyl or cyano; R5 is selected from hydrogen, chlorine or methyl.

[0007] Furthermore, the structural formula of the above-mentioned phenylacrylamide derivatives is selected from one of the following: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , .

[0008] A second aspect of the present invention provides a method for preparing the above-mentioned phenylacrylamide derivatives, comprising the following steps: reacting cinnamic acid or its derivatives with benzimidazole derivatives in a solvent in the presence of a condensing agent and a base to obtain phenylacrylamide derivatives.

[0009] Furthermore, the structural formula of the above-mentioned phenylacrylamide derivatives is selected from one of the following: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , .

[0010] Furthermore, the condensing agent mentioned above is 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride.

[0011] Furthermore, the aforementioned base is 4-dimethylaminopyridine.

[0012] Furthermore, the solvent mentioned above is dichloromethane.

[0013] Furthermore, in the above preparation method, cinnamic acid or its derivatives and benzimidazole derivatives are first dissolved in a solvent, and then a condensing agent and alkali are added under ice bath conditions; the ice bath is removed, the reaction is carried out for 14-18 hours, and the final product is obtained after purification.

[0014] Furthermore, the reaction lasted for 16 hours.

[0015] Further purification was performed using a silica gel column.

[0016] The third aspect of this invention provides the application of the above-mentioned phenylacrylamide derivatives in the preparation of drugs for the prevention and control of agricultural plant diseases or in the prevention and control of agricultural plant diseases.

[0017] Furthermore, the aforementioned agricultural plant diseases include rice sheath blight, barley root rot, wheat scab, and rapeseed sclerotinia stem rot.

[0018] A fourth aspect of the present invention provides a fungicide composition comprising the above-mentioned phenylacrylamide derivatives and a commercially available fungicide, wherein the commercially available fungicide is selected from any one or more of azoxystrobin, pyraclostrobin, prothioconazole, mancozeb, flutriafol, tebuconazole, prochloraz, cyazofamid, fluopyram, metalaxyl, difenoconazole, propiconazole, chlorothalonil, jinggangmycin, carbendazim, and cyazofamid.

[0019] Furthermore, the molar ratio of the above-mentioned phenylacrylamide derivatives to the above-mentioned commercially available bactericides is 1:(1-10). Furthermore, the molar ratio of the above-mentioned phenylacrylamide derivatives to commercially available bactericides is 1:(1-8).

[0020] Furthermore, the above-mentioned bactericide composition can be processed into emulsifiable concentrates, water emulsions, microemulsions, wettable powders, water-dispersible granules, or suspensions.

[0021] 3. Beneficial effects Compared with the prior art, the advantages of this invention are as follows: This invention provides a class of phenylacrylamide derivatives, their preparation methods, and applications. Using cinnamic acid as the parent skeleton, a series of novel phenylacrylamide derivatives were designed and synthesized through active substructure splicing and structural modification strategies. Bioactivity tests showed that these compounds exhibited varying degrees of inhibitory activity against *Rhizoctonia solani*, *Gnaphalium affine*, *Fusarium graminearum*, and *Sclerotinia sclerotiorum*, with some compounds showing good antifungal activity, particularly compound 35, which exhibited excellent broad-spectrum activity. Addressing the need for control of crop diseases caused by plant pathogenic fungi and the shortcomings of existing fungicides, the phenylacrylamide derivatives provided by this invention have the potential for further development as lead compounds for novel agricultural fungicides. Detailed Implementation

[0022] The present invention will be further described below with reference to specific embodiments.

[0023] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application pertains; the term “and / or” as used herein includes any and all combinations of one or more of the associated listed items.

[0024] Unless otherwise stated, all raw materials used in this invention were purchased from Anaiji Chemical (Anhui Zesheng Technology Co., Ltd.), and all had a purity of 98%. The mass spectrometer used was an OrbitrapExploris 120 mass spectrometer from Thermo Fisher Scientific, USA. The nuclear magnetic resonance spectrometers used were a Bruker AVANCE 400 and a Bruker AVANCE NEO600M nuclear magnetic resonance spectrometer.

[0025] The synthetic route for a class of phenylacrylamide derivatives provided by this invention is shown below: .

[0026] Cinnamic acid or its derivatives and benzimidazole derivatives (1 equivalent) were dissolved in dichloromethane. 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) (2 equivalents) and 4-dimethylaminopyridine (DMAP) (0.1 equivalents) were added under ice bath conditions. The ice bath was removed, and the reaction was carried out at room temperature for 16 hours. After the reaction was complete, the crude product precipitated and was purified by silica gel column chromatography (petroleum ether:ethyl acetate = 4:1, v / v) to obtain a series of phenylacrylamide derivatives.

[0027] Example 1 This embodiment provides N -(1 H -benzo[ d Preparation of imidazole-2-yl)phenylacrylamide (compound 1).

[0028] Cinnamic acid (0.667 mmol) was dissolved in 5 mL of dichloromethane, and 2-amino-1-ethylhexylene was added. H -benzo[ d Imidazole (0.667 mmol) was added to EDCI (1.3 mmol) and DMAP (0.06 mmol) under ice bath conditions. After reacting in an ice bath for 1 h, the reaction was carried out at room temperature (25 °C) for 16 h. The reaction progress was detected by TLC and compound 1 was obtained by column chromatography.

[0029] The developing solvent for thin-layer chromatography (TLC) was petroleum ether:ethyl acetate = 4:1, v / v. R f = 0.20.

[0030] The product is a yellow solid with a yield of 45%. Spectral information: 1 H NMR (400 MHz, DMSO-d6) δ 12.14 (s, 1H), 11.77 (s, 1H), 7.84 (dd, J = 6.7, 2.9 Hz, 1H), 7.64 (dd, J = 7.8, 1.9 Hz, 1H), 7.53 – 7.40(m, 5H), 7.30 – 7.17 (m, 2H), 7.14 (td, J = 7.6, 1.1 Hz, 1H), 7.08 (dd, J =5.9, 3.2 Hz, 1H). HRMS (ESI) m / z Calcd. for C 16 H 13 N3O [M + H]+: 263.1059; found: 263.1059. Based on the above information, the chemical formula of compound 1 can be identified as C.16 H 13 N3O has the following structure: .

[0031] Example 2 This embodiment provides ( E )- N -(1 H -benzo[ d Preparation of imidazole-2-yl)-3-(4-methylphenyl)acrylamide (compound 2).

[0032] The preparation method is the same as in Example 1. The only difference is that cinnamic acid is replaced with 4-methylcinnamic acid, resulting in compound 2.

[0033] The developing solvent for thin-layer chromatography (TLC) was petroleum ether:ethyl acetate = 4:1, v / v. R f = 0.26.

[0034] The product is a yellow solid with a yield of 49%. Spectral information: 1 H NMR (400 MHz, DMSO- d 6) δ 12.12 (s, 1H), 11.71 (s, 1H),7.73 – 7.64 (m, 1H), 7.53 (d, J = 7.9 Hz, 2H), 7.45 (s, 2H), 7.26 (d, J = 7.9Hz, 2H), 7.08 (q, J = 3.0, 2.5 Hz, 2H), 6.89 (d, J = 15.5 Hz, 1H), 2.33 (s,3H). HRMS (ESI) m / z Calculated for C 17 H 15 N3O[M + H] + : 278.1288; found: 278.1290. Based on the above information, the chemical formula of compound 2 can be identified as C. 17 H 15 N3O has the following structure: .

[0035] Example 3 This embodiment provides ( E )- N -(1 H-benzo[ d Preparation of imidazole-2-yl)-3-(4-methoxyphenyl)acrylamide (compound 3).

[0036] The preparation method is the same as in Example 1. The only difference is that cinnamic acid is replaced with 4-methoxycinnamic acid, resulting in compound 3.

[0037] The developing solvent for thin-layer chromatography (TLC) was petroleum ether:ethyl acetate = 4:1, v / v. R f = 0.22.

[0038] The product is a yellow solid with a yield of 53%. Spectral information: 1 H NMR (400 MHz, DMSO- d 6) δ 12.11 (s, 1H), 11.64 (s, 1H), 7.88 (d, J = 15.6 Hz, 1H), 7.84 – 7.78 (m, 2H), 7.43 (d, J = 8.0 Hz, 1H), 7.32(d, J = 15.6 Hz, 1H), 7.13 (td, J = 7.6, 1.1 Hz, 1H), 7.09 – 6.97 (m, 4H), 3.31(s, 3H). HRMS (ESI) m / z Calculated for C 17 H 15 N3O2[M + H] + : 294.1238; found:294.1235. Based on the above information, the chemical formula of compound 3 can be identified as C. 17 H 15 N3O2 has the following structure: .

[0039] Example 4 This embodiment provides ( E )- N -(1 H -benzo[ d Preparation of imidazole-2-yl)-3-(4-fluorophenyl)acrylamide (compound 4).

[0040] The preparation method is the same as in Example 1. The only difference is that cinnamic acid is replaced with 4-fluorocinnamic acid, resulting in compound 4.

[0041] The developing solvent for thin-layer chromatography (TLC) was petroleum ether:ethyl acetate = 4:1, v / v. R f = 0.25.

[0042] The product is a yellow solid with a yield of 57%. Spectral information: 1 H NMR (400 MHz, DMSO- d 6) δ 12.04 (s, 1H), 11.74 (s, 1H), 7.97 – 7.86 (m, 1H), 7.73 – 7.67 (m, 2H), 7.44 (d, J = 9.9 Hz, 2H), 7.31 (dt, J = 10.7, 8.5 Hz, 2H), 7.08 (dd, J = 6.0, 3.2 Hz, 2H), 6.89 (d, J = 15.8 Hz, 1H). HRMS (ESI) m / z Calculated for C 16 H 12 FN3O[M + H] + : 282.1038; found: 282.1039. Based on the above information, the chemical formula of compound 4 can be identified as C. 16 H 12 FN3O has the following structure: .

[0043] Example 5 This embodiment provides ( E )- N -(1 H -benzo[ d Preparation of imidazole-2-yl)-3-(4-chlorophenyl)acrylamide (compound 5).

[0044] The preparation method is the same as in Example 1. The only difference is that cinnamic acid is replaced with 4-chlorocinnamic acid, resulting in compound 5.

[0045] The developing solvent for thin-layer chromatography (TLC) was petroleum ether:ethyl acetate = 4:1, v / v. R f = 0.28.

[0046] The product is a yellow solid with a yield of 49%. Spectral information: 1H NMR (400 MHz, DMSO- d 6) δ 12.17 (s, 1H), 11.76 (s, 1H), 7.88 (d, J = 8.2 Hz, 2H), 7.55 (d, J = 8.4 Hz, 2H), 7.50 (d, J = 15.7 Hz, 1H), 7.43 (d, J = 8.0 Hz, 1H), 7.23 (d, J = 4.2 Hz, 2H), 7.18 – 7.10 (m, 1H), 7.04 –6.96 (m, 1H). HRMS (ESI) m / z Calculated for C 16 H 12 ClN3O[M + H] + : 298.0742; found:298.0741. Based on the above information, the chemical formula of compound 5 can be identified as C. 16 H 12 ClN3O has the following structure: .

[0047] Example 6 This embodiment provides ( E )- N -(1 H -benzo[ d Preparation of imidazole-2-yl)-3-(4-bromophenyl)acrylamide (compound 6).

[0048] The preparation method is the same as in Example 1. The only difference is that cinnamic acid is replaced with 4-bromocinnamic acid, resulting in compound 6.

[0049] The developing solvent for thin-layer chromatography (TLC) was petroleum ether:ethyl acetate = 4:1, v / v. R f = 0.22.

[0050] The product is a yellow solid with a yield of 46%. Spectral information: 1 H NMR (400 MHz, DMSO- d 6) δ 12.23 (s, 1H), 11.94 (s, 1H), 7.87 (d, J = 15.7 Hz, 1H), 7.74 (dd, J= 47.0, 8.3 Hz, 3H), 7.51 (d, J = 15.7Hz, 1H), 7.42 (d, J = 8.0 Hz, 1H), 7.22 (d, J = 13.1 Hz, 2H), 7.14 (t, J = 7.6Hz, 1H), 7.00 (t, J = 7.7 Hz, 1H). HRMS (ESI) m / z Calculated for C 16 H 12 BrN3O[M + H] + :342.0237; found: 342.0237. Based on the above information, the chemical formula of compound 6 can be identified as C. 16 H 12 BrN3O has the following structure: .

[0051] Example 7 This embodiment provides ( E )- N -(1 H -benzo[ d Preparation of imidazole-2-yl)-3-(2-methylphenyl)acrylamide (compound 7).

[0052] The preparation method is the same as in Example 1. The only difference is that cinnamic acid is replaced with 2-methylcinnamic acid, resulting in compound 7.

[0053] The developing solvent for thin-layer chromatography (TLC) was petroleum ether:ethyl acetate = 4:1, v / v. R f = 0.18.

[0054] The product was a white solid with a yield of 44%. Spectral information: 1 H NMR (400 MHz, DMSO- d 6) δ 12.12 (s, 1H), 11.96 (s, 1H), 7.95 (d, J = 15.7 Hz, 1H), 7.62 – 7.56 (m, 1H), 7.45 (t, J = 4.7 Hz, 2H), 7.34– 7.26 (m, 3H), 7.08 (dd, J= 6.0, 3.2 Hz, 2H), 6.85 (d, J = 15.7 Hz, 1H), 2.42(s, 3H). HRMS (ESI) m / z Calculated for C 17 H 15 N3O[M + H] + : 278.1288; found: 278.1280. Based on the above information, the chemical formula of compound 7 can be identified as C. 17 H 15 N3O has the following structure: .

[0055] Example 8 This embodiment provides ( E )- N -(1 H -benzo[ d Preparation of imidazole-2-yl)-3-(2-methoxyphenyl)acrylamide (compound 8).

[0056] The preparation method is the same as in Example 1. The only difference is that cinnamic acid is replaced with 2-methoxycinnamic acid, resulting in compound 8.

[0057] The developing solvent for thin-layer chromatography (TLC) was petroleum ether:ethyl acetate = 4:1, v / v. R f = 0.22.

[0058] The product is a yellow solid with a yield of 57%. Spectral information: 1 H NMR (400 MHz, DMSO- d 6) δ 12.12 (s, 1H), 11.97 (s, 1H), 8.06 (d, J = 15.8 Hz, 1H), 7.80 (d, J = 7.6 Hz, 1H), 7.58 (d, J = 15.7 Hz, 1H), 7.48 (d, J = 7.5 Hz, 2H), 7.22 (d, J = 8.0 Hz, 1H), 7.16 (d, J = 8.9 Hz, 2H), 7.04 (q, J = 8.4 Hz, 2H), 3.92 (s, 3H). HRMS (ESI) m / z Calculated for C 17 H 15 N3O2[M +H] + : 294.1238; found: 294.1239. Based on the above information, the chemical formula of compound 8 can be identified as C. 17 H 15 N3O2 has the following structure: .

[0059] Example 9 This embodiment provides ( E )- N -(1 H -benzo[ d Preparation of imidazole-2-yl)-3-(2-fluorophenyl)acrylamide (compound 9).

[0060] The preparation method is the same as in Example 1. The only difference is that cinnamic acid is replaced with 2-fluorocinnamic acid, resulting in compound 9.

[0061] The developing solvent for thin-layer chromatography (TLC) was petroleum ether:ethyl acetate = 4:1, v / v. R f = 0.26.

[0062] The product is a yellow solid with a yield of 53%. Spectral information: 1 H NMR (400 MHz, DMSO- d 6) δ 12.16 (s, 1H), 11.88 (s, 1H), 7.96 (t, J = 7.8 Hz, 1H), 7.91 (d, J = 15.8 Hz, 1H), 7.80 – 7.68 (m, 1H), 7.57(d, J = 15.9 Hz, 1H), 7.46 (d, J = 7.9 Hz, 1H), 7.24 (d, J = 9.0 Hz, 2H), 7.15(t, J = 7.6 Hz, 1H), 7.08 (dd, J = 6.5, 2.6 Hz, 1H), 7.05 – 6.98 (m, 1H). HRMS(ESI) m / z Calculated for C 16 H 12FN3O[M + H] + : 282.1038; found: 282.1041. Based on the above information, the chemical formula of compound 9 can be identified as C. 16 H 12 FN3O has the following structure: .

[0063] Example 10 This embodiment provides ( E )- N -(1 H -benzo[ d Preparation of imidazole-2-yl)-3-(2-chlorophenyl)acrylamide (compound 10).

[0064] The preparation method is the same as in Example 1. The only difference is that cinnamic acid is replaced with 2-chlorocinnamic acid, resulting in compound 10.

[0065] The developing solvent for thin-layer chromatography (TLC) was petroleum ether:ethyl acetate = 4:1, v / v. R f = 0.28.

[0066] The product is a yellow solid with a yield of 56%. Spectral information: 1 H NMR (400 MHz, DMSO- d 6) δ 12.06 (s, 1H), 11.89 (s, 1H), 8.06 – 7.95 (m, 1H), 7.78 – 7.74 (m, 1H), 7.57 (s, 1H), 7.47 (d, J = 4.0 Hz, 2H), 7.46 (d, J = 4.0 Hz, 2H), 7.09 (q, J = 3.2, 2.8 Hz, 2H), 6.96 (s, 1H). HRMS(ESI) m / z Calculated for C 16 H 12 ClN3O[M + H] + : 298.0742; found: 298.0744. Based on the above information, the chemical formula of compound 10 can be identified as C. 16 H 12 ClN3O has the following structure: .

[0067] Example 11 This embodiment provides ( E )- N -(1 H -benzo[ d Preparation of imidazole-2-yl)-3-(2-bromophenyl)acrylamide (compound 11).

[0068] The preparation method is the same as in Example 1. The only difference is that cinnamic acid is replaced with 2-bromocinnamic acid, resulting in compound 11.

[0069] The developing solvent for thin-layer chromatography (TLC) was petroleum ether:ethyl acetate = 4:1, v / v. R f = 0.31.

[0070] The product is a yellow solid with a yield of 51%. Spectral information: 1 H NMR (400 MHz, DMSO- d 6) δ 12.10 (s, 1H), 12.00 (s, 1H),8.01 – 7.93 (m, 1H), 7.73 (d, J = 7.7 Hz, 2H), 7.46 (d, J = 4.0 Hz, 2H), 7.36 (d, J = 8.0 Hz, 2H), 7.11 – 7.04 (m, 2H), 6.94 (d, J = 16.0 Hz, 1H). HRMS (ESI) m / z Calculated for C 16 H 12 BrN3O[M + H] + : 342.0237; found: 342.0236. Based on the above information, the chemical formula of compound 11 can be identified as C. 16 H 12 BrN3O has the following structure: .

[0071] Example 12 This embodiment provides ( E )- N -(1 H -benzo[ d Preparation of imidazole-2-yl)-3-(3,4-difluorophenyl)acrylamide (compound 12).

[0072] The preparation method is the same as in Example 1. The only difference is that cinnamic acid is replaced with 3,4-difluorocinnamic acid, resulting in compound 12.

[0073] The developing solvent for thin-layer chromatography (TLC) was petroleum ether:ethyl acetate = 4:1, v / v. R f = 0.21.

[0074] The product is a yellow solid with a yield of 48%. Spectral information: 1 H NMR (400 MHz, DMSO- d 6) δ 12.14 (s, 1H), 11.70 (s, 1H), 8.06 (dd, J = 11.7, 8.2 Hz, 1H), 7.87 (d, J = 15.7 Hz, 1H), 7.72 (s, 1H), 7.58– 7.48 (m, 2H), 7.43 (d, J = 8.0 Hz, 1H), 7.21 (d, J = 7.8 Hz, 1H), 7.14 (t, J =7.6 Hz, 1H), 7.01 (t, J = 7.6 Hz, 1H). HRMS (ESI) m / z Calculated for C 16 H 11 F2N3O[M +H] + : 300.0943; found: 300.0941. Based on the above information, the chemical formula of compound 12 can be identified as C. 16 H 11 F2N3O has the following structure: .

[0075] Example 13 This embodiment provides ( E )- N -(1 H -benzo[ d Preparation of imidazole-2-yl)-3-(2,4-difluorophenyl)acrylamide (compound 13).

[0076] The preparation method is the same as in Example 1. The only difference is that cinnamic acid is replaced with 2,4-difluorocinnamic acid, resulting in compound 13.

[0077] The developing solvent for thin-layer chromatography (TLC) was petroleum ether:ethyl acetate = 4:1, v / v. R f = 0.22.

[0078] The product is a yellow solid with a yield of 48%. Spectral information: 1 H NMR (400 MHz, DMSO- d 6) δ 12.17 (s, 1H), 11.74 (s, 1H), 8.06 (q, J = 8.1 Hz, 1H), 7.87 (d, J = 15.8 Hz, 1H), 7.54 (d, J = 15.9 Hz, 1H), 7.44 (t, J = 8.8 Hz, 2H), 7.22 (d, J = 7.8 Hz, 2H), 7.14 (t, J = 7.6 Hz, 1H), 7.01 (t, J = 7.7 Hz, 1H). HRMS (ESI) m / z Calculated for C 16 H 11 F2N3O[M + H] + :300.0943; found: 300.0941. Based on the above information, the chemical formula of compound 13 can be identified as C. 16 H 11 F2N3O has the following structure: .

[0079] Example 14 This embodiment provides ( E )- N -(1 H -benzo[ d Preparation of imidazole-2-yl)-3-(3-hydroxyphenyl)acrylamide (compound 14).

[0080] The preparation method is the same as in Example 1. Replacing cinnamic acid with 3-hydroxycinnamic acid yields compound 14.

[0081] The developing solvent for thin-layer chromatography (TLC) was petroleum ether:ethyl acetate = 4:1, v / v. R f = 0.28.

[0082] The product was a white solid with a yield of 52%. Spectral information: 1 H NMR (400 MHz, DMSO- d 6) δ 9.67 (s, 1H), 9.61 (s, 1H), 7.92 (s, 1H), 7.88 (s, 1H), 7.76 (d, J = 8.0 Hz, 2H), 7.72 (d, J = 6.0 Hz, 2H), 7.53(t, J = 8.4 Hz, 2H), 7.32 (d, J = 8.2 Hz, 1H), 6.98 (d, J = 15.7 Hz, 2H). HRMS(ESI) m / z Calculated for C 16 H 13 N3O2[M + H] + : 280.1081; found: 280.1081. Based on the above information, the chemical formula of compound 14 can be identified as C. 16 H 13 N3O2 has the following structure: .

[0083] Example 15 This embodiment provides N -(6-bromo-1 H -benzo[ d Preparation of imidazole-2-yl)cinnamamide (compound 15).

[0084] The preparation method is the same as in Example 1. 2-amino-1 H -benzo[ d Imidazole replaced with 6-bromo-2-amino-1 H -benzo[ d Imidazole was used to obtain compound 15.

[0085] The developing solvent for thin-layer chromatography (TLC) was petroleum ether:ethyl acetate = 4:1, v / v. R f = 0.18.

[0086] The product is a yellow solid with a yield of 57%. Spectral information: 1 H NMR (400 MHz, DMSO- d6) δ 12.30 (s, 1H), 11.85 (s, 1H), 7.73 (d, J = 15.7 Hz, 1H), 7.64 (d, J = 7.1 Hz, 3H), 7.45 (q, J = 15.7, 12.2 Hz,4H), 7.22 (dd, J = 8.3, 2.1 Hz, 1H), 6.94 (d, J = 15.7 Hz, 1H). HRMS (ESI) m / z Calculated for C 16 H 12 BrN3O[M + H] + : 342.0237; found: 342.0237. Based on the above information, the chemical formula of compound 15 can be identified as C. 16 H 12 BrN3O has the following structure: .

[0087] Example 16 This embodiment provides N -(6-methyl-1 H -benzo[ d Preparation of imidazole-2-yl)phenylacrylamide (compound 16).

[0088] The preparation method is the same as in Example 1. 2-amino-1 H -benzo[ d Imidazole replaced with 6-methyl-2-amino-1 H -benzo[ d Imidazole was used to obtain compound 16.

[0089] The developing solvent for thin-layer chromatography (TLC) was petroleum ether:ethyl acetate = 4:1, v / v. R f = 0.20.

[0090] The product was a white solid with a yield of 59%. Spectral information: 1 H NMR (400 MHz, DMSO- d 6) δ 11.92 (s, 1H), 11.79 (s, 1H), 7.71 (d, J= 15.8 Hz, 1H), 7.66 – 7.60 (m, 2H), 7.49 – 7.38 (m, 3H), 7.32 (d, J = 8.1 Hz, 1H), 7.25 (s, 1H), 6.98 – 6.87 (m, 2H), 2.36 (s, 3H). HRMS (ESI) m / z Calculated for C 17 H 15 N3O[M + H] + : 278.1288; found: 278.1287. Based on the above information, the chemical formula of compound 16 can be identified as C. 17 H 15 N3O has the following structure: .

[0091] Example 17 This embodiment provides N -(6-cyano-1) H -benzo[ d Preparation of imidazole-2-yl)cinnamamide (compound 17).

[0092] The preparation method is the same as in Example 1. 2-amino-1 H -benzo[ d Imidazole replaced with 6-cyano-2-amino-1 H -benzo[ d Imidazole was used to obtain compound 17.

[0093] The developing solvent for thin-layer chromatography (TLC) was petroleum ether:ethyl acetate = 4:1, v / v. R f = 0.22.

[0094] The product is a yellow solid with a yield of 49%. Spectral information: 1 H NMR (400 MHz, DMSO- d 6) δ 12.55 (s, 1H), 11.97 (s, 1H), 7.89 (d, J = 11.2 Hz, 1H), 7.76 (d, J = 15.5 Hz, 1H), 7.68 – 7.58 (m, 3H), 7.52– 7.43 (m, 4H), 6.96 (d, J= 15.8 Hz, 1H). HRMS (ESI) m / z Calculated for C 17 H 12 N4O[M+ H] + : 289.1084; found: 289.1087. Based on the above information, the chemical formula of compound 17 can be identified as C. 17 H 12 N4O has the following structure: .

[0095] Example 18 This embodiment provides N -(5,6-dimethyl-1 H -benzo[ d Preparation of imidazole-2-yl)phenylacrylamide (compound 18).

[0096] The preparation method is the same as in Example 1. 2-amino-1 H -benzo[ d Imidazole was replaced with 5,6-dimethyl-2-amino-1-yl H -benzo[ d Imidazole was used to obtain compound 18.

[0097] The developing solvent for thin-layer chromatography (TLC) was petroleum ether:ethyl acetate = 4:1, v / v. R f = 0.25.

[0098] The product was a white solid with a yield of 22%. Spectral information: 1 H NMR (400 MHz, DMSO- d 6) δ 11.89 (s, 1H), 11.71 (s, 1H),7.74 – 7.60 (m, 3H), 7.45 (q, J = 6.8 Hz, 3H), 7.22 (s, 2H), 6.92 (d, J = 15.8Hz, 1H), 2.26 (s, 6H). HRMS (ESI) m / z Calculated for C 18 H 17 N3O[M + H] + : 292.1445; found: 292.1444. Based on the above information, the chemical formula of compound 18 can be identified as C. 18H 17 N3O has the following structure: .

[0099] Example 19 This embodiment provides N -(1-methyl-1 H -benzo[ d Preparation of imidazole-2-yl)cinnamamide (compound 19).

[0100] The preparation method is the same as in Example 1. 2-amino-1 H -benzo[ d Imidazole replaced with 2-amino-1-methyl-1 H -benzo[ d Imidazole was used to obtain compound 19.

[0101] The developing solvent for thin-layer chromatography (TLC) was petroleum ether:ethyl acetate = 4:1, v / v. R f = 0.20.

[0102] The product was a purple solid, with a yield of 47%. Spectral information: 1 H NMR (400 MHz, DMSO- d 6) δ 12.58 (s, 1H), 7.64 (t, J = 9.9Hz, 3H), 7.51 (d, J = 7.4 Hz, 1H), 7.40 (d, J = 7.9 Hz, 4H), 7.27 – 7.15 (m,2H), 6.78 (s, 1H), 3.63 (s, 3H).HRMS (ESI) m / z Calculated for C 17 H 15 N3O[M + H] + :278.1288; found: 278.1282. Based on the above information, the chemical formula of compound 19 can be identified as C. 17 H 15 N3O has the following structure: .

[0103] Example 20 This embodiment provides ( E )- N -(1-methyl-1 H -benzo[d Preparation of imidazole-2-yl)-3-(4-methylphenyl)acrylamide (compound 20).

[0104] The preparation method is the same as in Example 1. Cinnamic acid is replaced with 4-methylcinnamic acid, and 2-amino-1-methylcinnamic acid is used instead. H -benzo[ d Imidazole replaced with 2-amino-1-methyl-1 H -benzo[ d Imidazole was used to obtain compound 20.

[0105] The developing solvent for thin-layer chromatography (TLC) was petroleum ether:ethyl acetate = 4:1, v / v. R f = 0.23.

[0106] The product was a purple solid with a yield of 52%. Spectral information: 1 H NMR (400 MHz, DMSO- d 6) δ 12.56 (s, 1H), 7.65 – 7.39 (m, 5H), 7.20 (p, J = 7.3 Hz, 4H), 6.70 (d, J = 14.7 Hz, 1H), 3.63 (s, 3H), 2.32(s, 3H). HRMS (ESI) m / z Calculated for C 18 H 17 N3O[M + H] + : 292.1445; found: 292.1440. Based on the above information, the chemical formula of compound 20 can be identified as C. 18 H 17 N3O has the following structure: .

[0107] Example 21 This embodiment provides ( E )- N -(1-methyl-1 H -benzo[ d Preparation of imidazole-2-yl)-3-(4-methoxyphenyl)acrylamide (compound 21).

[0108] The preparation method is the same as in Example 1. Cinnamic acid is replaced with 4-methoxycinnamic acid, and 2-amino-1... H -benzo[ d Imidazole replaced with 2-amino-1-methyl-1H -benzo[ d Imidazole was used to obtain compound 21.

[0109] The developing solvent for thin-layer chromatography (TLC) was petroleum ether:ethyl acetate = 4:1, v / v. R f = 0.22.

[0110] The product was a purple solid with a yield of 57%. Spectral information: 1 H NMR (400 MHz, DMSO- d 6) δ 12.54 (s, 1H), 7.60 (d, J = 8.4Hz, 3H), 7.53 – 7.37 (m, 2H), 7.20 (dt, J = 17.7, 7.3 Hz, 2H), 6.96 (d, J = 7.7Hz, 2H), 6.65 (s, 1H), 3.78 (s, 3H), 3.62 (s, 3H). HRMS (ESI) m / z Calcd. forC 18 H 17 N3O2[M + H] + : 308.1394; found: 308.1389. Based on the above information, the chemical formula of compound 21 can be identified as C. 18 H 17 N3O2 has the following structure: .

[0111] Example 22 This embodiment provides ( E )- N -(1-methyl-1 H -benzo[ d Preparation of imidazole-2-yl)-3-(4-fluorophenyl)acrylamide (compound 22).

[0112] The preparation method is the same as in Example 1. Cinnamic acid is replaced with 4-fluorocinnamic acid, and 2-amino-1-hydroxycinnamic acid is added to the cinnamic acid solution. H -benzo[ d Imidazole replaced with 2-amino-1-methyl-1 H -benzo[ d Imidazole was used to obtain compound 22.

[0113] The developing solvent for thin-layer chromatography (TLC) was petroleum ether:ethyl acetate = 4:1, v / v.R f = 0.21.

[0114] The product was a purple solid with a yield of 58%. Spectral information: 1 H NMR (400 MHz, DMSO- d 6) δ 12.57 (s, 1H), 7.73 (t, J = 6.9Hz, 2H), 7.62 (d, J = 15.9 Hz, 1H), 7.56 – 7.40 (m, 2H), 7.24 (d, J = 7.1 Hz, 2H), 7.19 (d, J = 8.7 Hz, 2H), 6.72 (d, J = 16.0 Hz, 1H), 3.63 (s, 3H). 13 C NMR (151 MHz, DMSO- d 6) δ 174.56, 163.92, 162.28, 152.76, 138.41,132.53, 130.41, 128.92, 122.95, 116.34, 116.20, 112.33, 109.90, 28.67. HRMS(ESI) m / z Calculated for C 17 H 14 FN3O[M + H] + : 296.1194; found: 296.1192. Based on the above information, the chemical formula of compound 22 can be identified as C. 17 H 14 FN3O has the following structure: .

[0115] Example 23 This embodiment provides ( E )- N -(1-methyl-1 H -benzo[ d Preparation of imidazole-2-yl)-3-(4-chlorophenyl)acrylamide (compound 23).

[0116] The preparation method is the same as in Example 1. Cinnamic acid is replaced with 4-chlorocinnamic acid, and 2-amino-1-methyl-2-ethylhexylene is added to the cinnamic acid solution. H -benzo[ dImidazole replaced with 2-amino-1-methyl-1 H -benzo[ d Imidazole was used to obtain compound 23.

[0117] The developing solvent for thin-layer chromatography (TLC) was petroleum ether:ethyl acetate = 4:1, v / v. R f = 0.26.

[0118] The product was a purple solid with a yield of 48%. Spectral information: 1 H NMR (400 MHz, DMSO- d 6) δ 12.58 (s, 1H), 7.70 (d, J = 8.0Hz, 2H), 7.60 (d, J = 15.8 Hz, 1H), 7.50 (d, J = 7.4 Hz, 2H), 7.45 (d, J = 8.0Hz, 2H), 7.21 (dt, J = 15.8, 7.3 Hz, 2H), 6.78 (d, J = 15.8 Hz, 1H), 3.63 (s,3H). HRMS (ESI) m / z Calculated for C 17 H 14 ClN3O[M + H] + : 312.0899; found: 312.0899. Based on the above information, the chemical formula of compound 23 can be identified as C. 17 H 14 ClN3O has the following structure: .

[0119] Example 24 This embodiment provides ( E )- N -(1-methyl-1 H -benzo[ d Preparation of imidazole-2-yl)-3-(4-bromophenyl)acrylamide (compound 24).

[0120] The preparation method is the same as in Example 1. Cinnamic acid is replaced with 4-bromocinnamic acid, and 2-amino-1... H -benzo[ d Imidazole replaced with 2-amino-1-methyl-1 H -benzo[d Imidazole was used to obtain compound 24.

[0121] The developing solvent for thin-layer chromatography (TLC) was petroleum ether:ethyl acetate = 4:1, v / v. R f = 0.28.

[0122] The product was a white solid with a yield of 53%. Spectral information: 1 H NMR (400 MHz, DMSO- d 6) δ 12.58 (s, 1H), 7.63 (d, J = 7.7Hz, 3H), 7.57 (d, J = 8.4 Hz, 2H), 7.47 (dd, J = 23.4, 7.4 Hz, 2H), 7.21 (dt, J = 16.0, 7.3 Hz, 2H), 6.79 (d, J = 7.4 Hz, 1H), 3.63 (s, 3H). HRMS (ESI) m / z Calculated for C 17 H 14 BrN3O[M + H] + : 356.0393; found: 356.0392. Based on the above information, the chemical formula of compound 24 can be identified as C. 17 H 14 BrN3O has the following structure: .

[0123] Example 25 This embodiment provides ( E )- N -(1-methyl-1 H -benzo[ d Preparation of imidazole-2-yl)-3-(2-methylphenyl)acrylamide (compound 25).

[0124] The preparation method is the same as in Example 1. Cinnamic acid is replaced with 2-methylcinnamic acid, and 2-amino-1... H -benzo[ d Imidazole replaced with 2-amino-1-methyl-1 H -benzo[ d Imidazole was used to obtain compound 25.

[0125] The developing solvent for thin-layer chromatography (TLC) was petroleum ether:ethyl acetate = 4:1, v / v. R f = 0.23.

[0126] The product was a white solid with a yield of 58%. Spectral information: 1 H NMR (400 MHz, DMSO- d 6) δ 12.60 (s, 1H), 7.90 (d, J = 15.7Hz, 1H), 7.68 (s, 1H), 7.47 (dd, J = 21.0, 7.2 Hz, 2H), 7.21 (dt, J = 15.8, 6.6Hz, 5H), 6.65 (d, J = 15.5 Hz, 1H), 3.63 (s, 3H), 2.40 (s, 3H). HRMS (ESI) m / z Calculated for C 18 H 17 N3O[M + H] + : 292.1445; found: 292.1442. Based on the above information, the chemical formula of compound 25 can be identified as C. 18 H 17 N3O has the following structure: .

[0127] Example 26 This embodiment provides ( E )- N -(1-methyl-1 H -benzo[ d Preparation of imidazole-2-yl)-3-(2-methoxyphenyl)acrylamide (compound 26).

[0128] The preparation method is the same as in Example 1. Cinnamic acid is replaced with 2-methoxycinnamic acid, and 2-amino-1... H -benzo[ d Imidazole replaced with 2-amino-1-methyl-1 H -benzo[ d Imidazole was used to obtain compound 26.

[0129] The developing solvent for thin-layer chromatography (TLC) was petroleum ether:ethyl acetate = 4:1, v / v. R f = 0.20.

[0130] The product was a purple solid with a yield of 53%. Spectral information: 1 H NMR (400 MHz, DMSO- d 6) δ 12.56 (s, 1H), 7.89 (d, J = 16.0Hz, 1H), 7.65 (s, 1H), 7.54 – 7.31 (m, 3H), 7.20 (d, J = 4.0 Hz, 2H), 7.02 (d, J = 19.0 Hz, 2H), 6.74 (d, J = 16.1 Hz, 1H), 3.87 (s, 3H), 3.62 (s, 3H). HRMS(ESI) m / z Calculated for C 18 H 17 N3O2[M + H] + : 308.1394; found: 308.1394. Based on the above information, the chemical formula of compound 26 can be identified as C. 18 H 17 N3O2 has the following structure: .

[0131] Example 27 This embodiment provides ( E )- N -(1-methyl-1 H -benzo[ d Preparation of imidazole-2-yl)-3-(2-fluorophenyl)acrylamide (compound 27).

[0132] The preparation method is the same as in Example 1. Cinnamic acid is replaced with 2-fluorocinnamic acid, and 2-amino-1... H -benzo[ d Imidazole replaced with 2-amino-1-methyl-1 H -benzo[ d Imidazole was used to obtain compound 27.

[0133] The developing solvent for thin-layer chromatography (TLC) was petroleum ether:ethyl acetate = 4:1, v / v. R f = 0.21.

[0134] The product was a purple solid with a yield of 55%. Spectral information:1 H NMR (400 MHz, DMSO- d 6) δ 12.62 (s, 1H), 7.82 (d, J = 7.6Hz, 1H), 7.73 (d, J = 16.0 Hz, 1H), 7.51 (d, J = 7.5 Hz, 1H), 7.45 (d, J = 7.8Hz, 1H), 7.40 (d, J = 7.2 Hz, 1H), 7.29 – 7.23 (m, 2H), 7.23 – 7.14 (m, 2H), 6.84 (d, J = 16.0 Hz, 1H), 3.63 (s, 3H). HRMS (ESI) m / z Calculated for C 17 H 14 FN3O[M +H] + : 296.1194; found: 296.1194. Based on the above information, the chemical formula of compound 27 can be identified as C. 17 H 14 FN3O has the following structure: .

[0135] Example 28 This embodiment provides ( E )- N -(1-methyl-1 H -benzo[ d Preparation of imidazole-2-yl)-3-(2-chlorophenyl)acrylamide (compound 28).

[0136] The preparation method is the same as in Example 1. Cinnamic acid is replaced with 2-chlorocinnamic acid, and 2-amino-1... H -benzo[ d Imidazole replaced with 2-amino-1-methyl-1 H -benzo[ d Imidazole was used to obtain compound 28.

[0137] The developing solvent for thin-layer chromatography (TLC) was petroleum ether:ethyl acetate = 4:1, v / v. R f = 0.25.

[0138] The product was a purple solid with a yield of 48%. Spectral information:1 H NMR (400 MHz, DMSO- d 6) δ 12.64 (s, 1H), 7.98 (d, J = 15.8Hz, 1H), 7.91 (s, 1H), 7.51 (q, J = 3.9, 3.4 Hz, 2H), 7.46 (d, J = 7.6 Hz, 1H), 7.38 (t, J = 4.5 Hz, 2H), 7.28 – 7.16 (m, 2H), 6.83 (d, J = 15.9 Hz, 1H), 3.64(s, 3H). HRMS (ESI) m / z Calculated for C 17 H 14 ClN3O[M + H] + : 312.0899; found:312.0901. Based on the above information, the chemical formula of compound 28 can be identified as C. 17 H 14 ClN3O has the following structure: .

[0139] Example 29 This embodiment provides ( E )- N -(1-methyl-1 H -benzo[ d Preparation of imidazole-2-yl)-3-(2-bromophenyl)acrylamide (compound 29).

[0140] The preparation method is the same as in Example 1. Cinnamic acid is replaced with 2-bromocinnamic acid, and 2-amino-1... H -benzo[ d Imidazole replaced with 2-amino-1-methyl-1 H -benzo[ d Imidazole was used to obtain compound 29.

[0141] The developing solvent for thin-layer chromatography (TLC) was petroleum ether:ethyl acetate = 4:1, v / v. R f = 0.28.

[0142] The product was a purple solid, with a yield of 47%. Spectral information: 1 H NMR (400 MHz, DMSO-d 6) δ 12.64 (s, 1H), 7.98 – 7.85 (m, 2H), 7.69 (d, J = 7.8 Hz, 1H), 7.50 (d, J = 7.2 Hz, 1H), 7.48 – 7.36 (m, 2H), 7.30 (s, 1H), 7.22 (p, J = 7.2 Hz, 2H), 6.78 (d, J = 15.7 Hz, 1H), 3.64 (s,3H). HRMS (ESI) m / z Calculated for C 17 H 14 BrN3O[M + H] + : 356.0394; found: 356.0391. Based on the above information, the chemical formula of compound 29 can be identified as C. 17 H 14 BrN3O has the following structure: .

[0143] Example 30 This embodiment provides ( E )- N -(1-methyl-1 H -benzo[ d Preparation of imidazole-2-yl)-3-(3,4-difluorophenyl)acrylamide (compound 30).

[0144] The preparation method is the same as in Example 1. Cinnamic acid is replaced with 3,4-difluorocinnamic acid, and 2-amino-1... H -benzo[ d Imidazole replaced with 2-amino-1-methyl-1 H -benzo[ d Imidazole was used to obtain compound 30.

[0145] The developing solvent for thin-layer chromatography (TLC) was petroleum ether:ethyl acetate = 4:1, v / v. R f = 0.22.

[0146] The product was a purple solid with a yield of 51%. Spectral information: 1 H NMR (400 MHz, DMSO- d 6) δ 12.58 (s, 1H), 7.84 (s, 1H), 7.58(d,J = 16.4 Hz, 1H), 7.51 (d, J = 10.5 Hz, 2H), 7.44 (d, J = 7.5 Hz, 2H), 7.21(p, J = 7.2 Hz, 2H), 6.79 (d, J = 15.8 Hz, 1H), 3.63 (s, 3H). HRMS (ESI) m / z Calculated for C 17 H 13 F2N3O[M + H] + : 314.1100; found: 314.1096. Based on the above information, the chemical formula of compound 30 can be identified as C. 17 H 13 F2N3O has the following structure: .

[0147] Example 31 This embodiment provides ( E )-2-methyl- N -(1-methyl-1 H -benzo[ d Preparation of imidazole-2-yl)-3-phenylacrylamide (compound 31).

[0148] The preparation method is the same as in Example 1. Cinnamic acid is replaced with ( E )-2-methyl-3-phenylacrylic acid, with 2-amino-1 H -benzo[ d Imidazole replaced with 2-amino-1-methyl-1 H -benzo[ d Imidazole was used to obtain compound 31.

[0149] The developing solvent for thin-layer chromatography (TLC) was petroleum ether:ethyl acetate = 4:1, v / v. R f = 0.38.

[0150] The product was a purple solid with a yield of 53%. Spectral information: 1 H NMR (400 MHz, DMSO- d 6) δ 12.58 (s, 1H), 7.91 (s, 1H), 7.48(d, J = 7.5 Hz, 2H), 7.44 (d,J = 6.6 Hz, 2H), 7.40 (d, J = 7.6 Hz, 2H), 7.30(t, J = 7.0 Hz, 1H), 7.26 – 7.14 (m, 2H), 3.64 (s, 3H), 2.16 (s, 3H). HRMS(ESI) m / z Calculated for C 18 H 17 N3O[M + H] + : 292.1445; found: 292.1443. Based on the above information, the chemical formula of compound 31 can be identified as C. 18 H 17 N3O has the following structure: .

[0151] Example 32 This embodiment provides ( E )-2-methyl- N -(1 H -benzo[ d Preparation of imidazole-2-yl)-3-phenylacrylamide (compound 32).

[0152] The preparation method is the same as in Example 1. Cinnamic acid is replaced with ( E )-2-methyl-3-phenylacrylic acid, yielding compound 32.

[0153] The developing solvent for thin-layer chromatography (TLC) was petroleum ether:ethyl acetate = 4:1, v / v. R f = 0.22.

[0154] The product was a white solid with a yield of 54%. Spectral information: 1 H NMR (400 MHz, DMSO- d 6) δ 11.98 (s, 1H), 11.94 (s, 1H), 7.58 (s, 1H), 7.45 (q, J = 7.7, 6.3 Hz, 6H), 7.36 (d, J = 7.4 Hz, 1H), 7.09(dd, J = 6.3, 3.2 Hz, 2H), 2.14 (s, 3H). 13C NMR (151 MHz, DMSO- d 6) δ 170.44, 148.53, 136.28, 135.62, 132.17,129.97, 128.95, 128.62, 121.68, 114.16, 14.72. HRMS (ESI) m / z Calcd. forC 17 H 15 N3O[M + H] + : 278.1288; found: 278.1285. Based on the above information, the chemical formula of compound 32 can be identified as C. 17 H 15 N3O has the following structure: .

[0155] Example 33 This embodiment provides ( E )-2-methyl- N -(6-bromo-1 H -benzo[ d Preparation of imidazole-2-yl)-3-phenylacrylamide (compound 33).

[0156] The preparation method is the same as in Example 1. Cinnamic acid is replaced with ( E )-2-methyl-3-phenylacrylic acid, and 2-amino-1 H -benzo[ d Imidazole replaced with 6-bromo-2-amino-1 H -benzo[ d Imidazole was used to obtain compound 33.

[0157] The developing solvent for thin-layer chromatography (TLC) was petroleum ether:ethyl acetate = 4:1, v / v. R f = 0.20.

[0158] The product was a white solid with a yield of 46%. Spectral information: 1 H NMR (400 MHz, DMSO- d 6) δ 12.32 (s, 1H), 11.75 (s, 1H), 7.61 (s, 1H), 7.56 (s, 1H), 7.46 (q, J = 7.9 Hz, 4H), 7.41 – 7.32 (m, 2H), 7.23 (d, J= 8.5 Hz, 1H), 2.13 (s, 3H). 13 C NMR (151 MHz, DMSO- d 6) δ 176.39, 160.44, 150.22, 144.00, 139.85,135.91, 135.84, 134.98, 133.89, 126.96, 123.22, 121.05, 119.27, 20.07. HRMS(ESI) m / z Calculated for C 17 H 14 BrN3O[M + H] + : 356.0393; found: 356.0397. Based on the above information, the chemical formula of compound 33 can be identified as C. 17 H 14 BrN3O has the following structure: .

[0159] Example 34 This embodiment provides ( E )-2-methyl- N -(6-methyl-1 H -benzo[ d Preparation of imidazole-2-yl)-3-phenylacrylamide (compound 34).

[0160] The preparation method is the same as in Example 1. Cinnamic acid is replaced with ( E )-2-methyl-3-phenylacrylic acid, with 2-amino-1 H -benzo[ d Imidazole replaced with 6-methyl-2-amino-1 H -benzo[ d Imidazole was used to obtain compound 34.

[0161] The developing solvent for thin-layer chromatography (TLC) was petroleum ether:ethyl acetate = 4:1, v / v. R f = 0.22.

[0162] The product was a white solid with a yield of 52%. Spectral information: 1 H NMR (400 MHz, DMSO- d6) δ 11.88 (s, 1H), 11.85 (s, 1H), 7.58 (s, 1H), 7.50 – 7.39 (m, 4H), 7.35 (d, J = 6.7 Hz, 1H), 7.30 (d, J = 8.1Hz, 1H), 7.22 (s, 1H), 6.91 (dd, J = 8.1, 1.7 Hz, 1H), 2.36 (s, 3H), 2.13 (s,3H). HRMS (ESI) m / z Calculated for C 18 H 17 N3O[M + H] + : 292.1445; found: 292.1440. Based on the above information, the chemical formula of compound 34 can be identified as C. 18 H 17 N3O has the following structure: .

[0163] Example 35 This embodiment provides ( E )-2-methyl- N -(6-cyano-1) H -benzo[ d Preparation of imidazole-2-yl)-3-phenylacrylamide (compound 35).

[0164] The preparation method is the same as in Example 1. Cinnamic acid is replaced with ( E )-2-methyl-3-phenylacrylic acid, with 2-amino-1 H -benzo[ d Imidazole replaced with 6-cyano-2-amino-1 H -benzo[ d Imidazole was used to obtain compound 35.

[0165] The developing solvent for thin-layer chromatography (TLC) was petroleum ether:ethyl acetate = 4:1, v / v. R f = 0.25.

[0166] The product was a white solid with a yield of 54%. Spectral information: 1 H NMR (400 MHz, DMSO- d6) δ 12.59 (s, 1H), 11.93 (s, 1H), 7.88 (s, 1H), 7.63 – 7.55 (m, 2H), 7.52 – 7.41 (m, 5H), 7.40 – 7.32 (m, 1H), 2.14 (s, 3H). 13 C NMR (151 MHz, DMSO- d 6) δ 174.44, 155.00, 142.86, 141.26, 141.24,140.68, 135.90, 134.78, 133.71, 133.68, 133.60, 132.87, 130.20, 125.45,108.03, 19.37. HRMS (ESI) m / z Calculated for C 18 H 14 N4O[M + H] + : 303.1241; found:303.1242. Based on the above information, the chemical formula of compound 35 can be identified as C. 18 H 14 N4O has the following structure: .

[0167] Example 36 This embodiment provides ( E )-2-methyl- N -(5,6-dimethyl-1 H -benzo[ d Preparation of imidazole-2-yl)-3-phenylacrylamide (compound 36).

[0168] The preparation method is the same as in Example 1. Cinnamic acid is replaced with ( E )-2-methyl-3-phenylacrylic acid, with 2-amino-1 H -benzo[ d Imidazole was replaced with 5,6-dimethyl-2-amino-1-yl H -benzo[ d Imidazole was used to obtain compound 36.

[0169] The developing solvent for thin-layer chromatography (TLC) was petroleum ether:ethyl acetate = 4:1, v / v. R f = 0.21.

[0170] The product was a white solid with a yield of 49%. Spectral information:1 H NMR (400 MHz, DMSO- d 6) δ 11.82 (s, 1H), 11.78 (s, 1H), 7.58 (s, 1H), 7.49 – 7.39 (m, 4H), 7.37 – 7.30 (m, 1H), 7.19 (s, 2H), 2.25 (s, 6H), 2.13 (s, 3H). HRMS (ESI) m / z Calculated for C 19 H 19 N3O[M + H] + : 306.1601; found: 306.1597. Based on the above information, the chemical formula of compound 36 can be identified as C. 19 H 19 N3O has the following structure: .

[0171] Example 37 This embodiment provides ( E )-2-methyl- N -(5,6-dichloro-1 H -benzo[ d Preparation of imidazole-2-yl)-3-phenylacrylamide (compound 37).

[0172] The preparation method is the same as in Example 1. Cinnamic acid is replaced with ( E )-2-methyl-3-phenylacrylic acid, with 2-amino-1 H -benzo[ d Imidazole was replaced with 5,6-dichloro-2-amino-1 H -Benzi[d]imidazole, yielding compound 37.

[0173] The developing solvent for thin-layer chromatography (TLC) was petroleum ether:ethyl acetate = 4:1, v / v. R f = 0.20.

[0174] The product is a white solid with a yield of 55%. Spectral information: 1 H NMR (400 MHz, DMSO- d 6) δ 12.44 (s, 1H), 11.81 (s, 1H), 7.66 (s, 2H), 7.55 (d, J= 1.7 Hz, 1H), 7.51 – 7.41 (m, 4H), 7.41 – 7.32 (m,1H), 2.13 (s, 3H). HRMS (ESI) m / z Calculated for C 17 H 13 Cl2N3O[M + H] + : 346.0509;found: 346.0505. Based on the above information, the chemical formula of compound 37 can be identified as C. 17 H 13 Cl2N3O has the following structure: .

[0175] Example 38 This embodiment provides the determination of the antifungal activity of the phenylacrylamide derivatives prepared in Examples 1-37 above.

[0176] Select rice sheath blight pathogen ( Rhizoctonia solani ), Barley root rot pathogen ( Fusarium avenaceum ), wheat scab ( Fusarium graminearum ) and rapeseed sclerotinia ( Sclerotinia sclerotiorum Four pathogenic fungi were used as test strains, all of which were derived from the College of Plant Protection, Nanjing Agricultural University. The test strains were pre-inoculated onto PDA agar plates for activation, and the antibacterial activity of the test compounds was determined using the mycelial growth rate method.

[0177] PDA medium preparation: Weigh 200g of potatoes, peel and slice them, then boil them in 1L of pure water for 20 minutes, until the potatoes can be easily crushed. Filter the solution through 8 layers of gauze, collect the filtrate, add 20g of glucose and 20g of agar, stir well, and then add an appropriate amount of pure water to a final volume of 1L. Dispense the solution into 250mL Erlenmeyer flasks (100mL per flask) and autoclave at 121℃ for 20 minutes.

[0178] The tested compound 1-37 and the control drugs azoxystrobin and tebuconazole (both azoxystrobin and tebuconazole were obtained from the College of Biological Protection, Nanjing Agricultural University) were weighed and completely dissolved in 0.1 mL of DMSO. This solution was then added to 100 mL of melted PDA medium cooled to 80°C, quickly mixed, and poured into petri dishes to prepare drug-containing plates. The EC50 of the target compound against four fungi was then determined. 50At the time of evaluation, the concentrations of the test compounds in the culture medium were set to 50, 40, 30, 20, 10, 5, 2.5, 1, 0.4, and 0.2 μg / mL, respectively. The final concentration of DMSO was 0.1%, and this concentration had been shown to have no significant effect on the growth of the tested fungi. A culture medium containing 0.1% DMSO (v / v) was used as a blank control. After the culture medium solidified, a 5 mm diameter mycelial disc was cut from the edge of the pre-activated colony and placed in the center of the culture medium. The petri dishes were incubated at 28°C for 72 h. Each treatment was repeated three times. After the incubation period, the colony diameter (mm) was measured in two different directions using calipers, and the average value was taken. Using IBM SPSS Statistics 26 software, the probability value (y) was converted from the mycelial growth inhibition rate, and a linear regression analysis was performed with the logarithm of the agent mass concentration as the independent variable (x) to calculate the toxicity regression equation and the half-maximal effective concentration (EC50). 50 ).

[0179] .

[0180] Table 1. Inhibition rates (%) of compounds 1-37, azoxystrobin, and tebuconazole against four plant pathogenic fungi at a concentration of 50 μg / mL.

[0181] Table 2. EC50 of some compounds, pyraclostrobin, and tebuconazole against four plant pathogenic fungi. 50 value

[0182] The results are shown in Tables 1 and 2 above. The phenylacrylamide derivatives of this invention all exhibited varying degrees of inhibitory effects on the mycelial growth of four plant pathogenic fungi. Compound 35, in particular, showed good broad-spectrum antifungal activity against *Rhizoctonia solani* (rice sheath blight), *Sclerotinia sclerotiorum* (rapeseed sclerotiorum), *Gnaphalium affine* (barley root rot), and *Fusarium graminearum* (wheat scab). Its EC50... 50 The values ​​were 0.284, 0.685, 1.524 and 1.806 μg / mL, respectively, indicating their potential for further development as lead compounds for novel agricultural fungicides.

Claims

1. A class of phenylacrylamide derivatives, characterized in that, The general structural formula of the phenylacrylamide derivatives is shown in Formula I below: ， Wherein, R1 is selected from phenyl or phenyl mono- or di-substituted by fluorine, chlorine, bromine, methyl, methoxy, nitro or hydroxyl; R2 is selected from hydrogen or methyl; R3 is selected from hydrogen or methyl; R4 is selected from hydrogen, chlorine, methyl or cyano; R5 is selected from hydrogen, chlorine or methyl.

2. The phenylacrylamide derivative according to claim 1, characterized in that, The structural formula of the phenylacrylamide derivative is selected from one of the following: ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， 。 3. The method for preparing the phenylacrylamide derivative according to claim 1 or 2, characterized in that, The process includes the following steps: reacting cinnamic acid or its derivatives with benzimidazole derivatives in a solvent in the presence of a condensing agent and a base to obtain phenylacrylamide derivatives.

4. The method for preparing phenylacrylamide derivatives according to claim 3, characterized in that, The structural formula of the phenylacrylamide derivative is selected from one of the following: ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， 。 5. The method for preparing phenylacrylamide derivatives according to claim 4, characterized in that, The condensing agent is 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride; the base is 4-dimethylaminopyridine; and the solvent is dichloromethane.

6. The method for preparing phenylacrylamide derivatives according to any one of claims 3-5, characterized in that, First, cinnamic acid or its derivatives and benzimidazole derivatives are dissolved in a solvent. Then, a condensing agent and a base are added under ice bath conditions. The ice bath is removed, and the reaction is carried out for 14-18 hours. The final product is then purified.

7. The use of the phenylacrylamide derivatives as described in claim 1 or 2 in the preparation of drugs for the prevention and control of agricultural plant diseases or in the prevention and control of agricultural plant diseases.

8. The application according to claim 7, characterized in that, The agricultural plant diseases mentioned include rice sheath blight, barley root rot, wheat scab, and rapeseed sclerotinia stem rot.

9. A bactericide composition, characterized in that, The fungicide composition comprises the phenylacrylamide derivative of claim 1 or 2 and a commercially available fungicide, wherein the commercially available fungicide is selected from any one or more of azoxystrobin, pyraclostrobin, prothioconazole, mancozeb, flutriafol, tebuconazole, prochloraz, cyazofamid, fluopyram, metalaxyl, difenoconazole, propiconazole, chlorothalonil, jinggangmycin, carbendazim, and cyazofamid.

10. The bactericidal composition according to claim 9, characterized in that, The molar ratio of the phenylacrylamide derivative to the commercially available bactericide is 1:(1-10).

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