Alpha-brominated acrylamide compound and application thereof

Abstract

The invention relates to the technical field of organic matter synthesis, in particular to an alpha-bromo-acrylamide compound and application thereof. The structural formula adopted by the invention is # imgabs0 #. The invention also relates to an application of the compound in preparation of drugs for resisting plant pathogenic fungi. The alpha-brominated acrylamide compound has the advantages of simple structure, easiness in synthesis, high antibacterial activity, wide antibacterial spectrum, low toxicity to animals and plants and low cost, and has great potential in the aspect of developing novel efficient antibacterial drugs.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthesis, and particularly relates to a class of α-bromoacrylamide compounds and their applications. Background Art

[0002] Plant pathogenic microorganisms are an important cause of plant diseases, and about two-thirds of plant diseases are caused by plant pathogenic fungi. More than 19,000 species of plant pathogenic fungi have been reported so far. These fungi not only seriously affect the growth and development of plants, but may also cause plant death in some cases. At the same time, some plant pathogenic fungi can produce mycotoxins, which can cause cancer or damage the central nervous system, affecting the health of humans and animals. Therefore, the use of fungicides to control plant diseases plays a key role in agricultural production and food safety.

[0003] For the better growth of plants, the blind, long-term and large-scale unreasonable use of fungicides has led to serious problems such as drug resistance, environmental pollution, and pesticide residues. This has caused some commercially used fungicides to be gradually phased out of the market. Therefore, it is crucial for agricultural development to discover new compounds with novel molecular skeletons, mechanisms of action and environmental friendliness.

[0004] The α,β-unsaturated carbonyl fragment widely exists in natural products and synthetic compounds and has various biological activities such as insecticidal, antibacterial, antifungal, and anticancer. As a Michael acceptor, acrylamide is the most commonly used fragment in the design of TCIs. So far, only a few literatures have reported that α-bromoacrylic acid compounds have nematicidal and anticancer activities. There is no relevant report on the inhibitory activity of 3-phenyl-2,3-dibromopropionate compounds or analogs specifically against plant pathogenic fungi. Summary of the Invention

[0005] In order to solve the problems that plants are resistant to existing fungicides, environmental pollution and serious pesticide residues lead to being phased out of the market, and new compounds need to be developed to expand the market, the present invention provides an α-bromoacrylamide compound and its application, and the compound has good inhibitory activity against plant pathogenic fungi.

[0006] To achieve the above objectives, the present invention provides the following technical solutions: a class of α-bromoacrylamide compounds, the structural formula of which is:

[0007]

[0008] Wherein:

[0009] Compound A1: R is ortho-fluoro, chloro, bromo, iodo, trifluoromethyl, cyano, methoxy, nitro, isopropyl; 3-isopropyl; 4-cyano; 2,3-dimethyl; 2,5-dimethyl; 2,6-dimethyl; 3,5-dimethyl; 3,5-dibromo; 2-methyl, 4-fluoro; 2-fluoro, 4-methyl;

[0010] Compound A2: The carbon number n is 2 or 3 respectively.

[0011] A class of α-bromoacrylamide compounds with excellent antibacterial activity, the structural formula is:

[0012]

[0013] Compound A1: R is ortho-, para- or meta-methyl, nitro, hydroxy, cyano, isopropyl, fluoro, chloro, bromo, iodo; 2,3-dimethyl, 2,5-dimethyl, 2,6-dimethyl, 3,4-dimethyl, 3,5-dimethyl, 3,5-dibromo; 2-methyl, 4-fluoro, 2-fluoro, 4-methyl, 2-methoxy, 3-methoxy, 2-trifluoromethyl, 3-trifluoromethyl;

[0014] Compound A2: The carbon number n is 1, 2 or 3 respectively.

[0015] Use of the above α-bromoacrylamide compounds in the preparation of plant antifungal drugs.

[0016] The above α-bromoacrylamide compounds can be used as a single active ingredient or in combination with other antibacterial drugs in the preparation of plant antifungal drugs.

[0017] The above α-bromoacrylamide compounds have significant inhibitory activity against the following plant pathogenic bacteria:

[0018] Fusarium oxysporum f. sp. vasinfectum, Fusarium oxysporum f. sp. niveum, Fusarium coeruleum, Gibberella zeae, Alternaria solani, Alternaria brassicae, Alternaria alternata, Curvularia lunata, Colletotrichum gloeosporioides, Fusarium oxysporum f. sp. cucumerinum, Valsa mali, Magnaporthe oryzae, Physalospora piricola; Sphaerotheca fuliginea; Plasmopara viticola.

[0019] Application of the above α-bromoacrylamide antibacterial drugs, characterized in that the drugs have a significant effect on preventing or treating the following plant fungal diseases:

[0020] Fusarium wilt of watermelon, Gibberella zeae of wheat, Alternaria solani of tomato, Alternaria brassicae of Chinese cabbage, Alternaria alternata of tobacco, Curvularia lunata of maize, Colletotrichum gloeosporioides of apple, Fusarium oxysporum f. sp. cucumerinum of pumpkin, Magnaporthe oryzae of rice, Physalospora piricola of apple; Sphaerotheca fuliginea of muskmelon; Plasmopara viticola of grape.

[0021] Compared with the prior art, the present invention has the following advantages:

[0022] 1) The α-bromoacrylamide compounds of the present invention have a simple structure and are easy to synthesize, and have great potential in the development of new and highly effective antibacterial drugs.

[0023] 2) The α-bromoacrylamide compounds of the present invention have excellent antibacterial activity.

[0024] 3) The α-bromoacrylamide compounds of the present invention have the characteristics of a broad antibacterial spectrum. Detailed Description of the Invention

[0025] The present invention will be described in detail below in conjunction with specific embodiments.

[0026] A class of α-bromoacrylamide compounds, the structural formula is:

[0027]

[0028] Wherein:

[0029] Compound A1: R is ortho-fluoro, chloro, bromo, iodo, trifluoromethyl, cyano, methoxy, nitro, isopropyl; 3-isopropyl; 4-cyano; 2,3-dimethyl; 2,5-dimethyl; 2,6-dimethyl; 3,5-dimethyl; 3,5-dibromo; 2-methyl, 4-fluoro; 2-fluoro, 4-methyl;

[0030] Compound A2: The carbon number n is 2 or 3 respectively.

[0031] A class of α-bromoacrylamide compounds with excellent antibacterial activity, the structural formula is:

[0032]

[0033] Wherein:

[0034] Compound A1: R is ortho-, para- or meta-methyl, nitro, hydroxy, cyano, isopropyl, fluoro, chloro, bromo, iodo; 2,3-dimethyl, 2,5-dimethyl, 2,6-dimethyl, 3,4-dimethyl, 3,5-dimethyl, 3,5-dibromo; 2-methyl, 4-fluoro, 2-fluoro, 4-methyl, 2-methoxy, 3-methoxy, 2-trifluoromethyl, 3-trifluoromethyl;

[0035] Compound A2: The carbon number n is 1, 2 or 3 respectively.

[0036] The preparation method of the above-mentioned α-bromoacrylamide compounds comprises the following steps:

[0037] Precisely weigh acrylic acid (5 mmol) and place it in a 100 mL reaction flask, then add dichloromethane (DCM). After stirring for 10 minutes, slowly add liquid bromine (6 mmol) to the reaction system under an ice bath environment, and then transfer the reaction system to room temperature. After stirring for about 10 hours, the color of the reaction solution changes from red to yellow, and at this time, the reaction is considered complete. Remove the excess bromine with a 10% sodium thiosulfate solution. Dilute the reaction system with water, and then extract it with ethyl acetate (3 × 30 mL). Combine the organic phases, dry over anhydrous sodium sulfate, filter, and concentrate under reduced pressure to obtain the crude product 2,3-dibromopropionic acid (b). Add 20 mL of 1,2-dichloroethane (DCE) and thionyl chloride (6 mmol) to the reaction flask containing the crude product b. Heat the reaction system under reflux at 80 °C for 2 hours. After the reaction is complete, concentrate the reaction system to obtain the crude product 2,3-dibromopropionyl chloride with different substituents, and this crude product can be directly used for subsequent reactions without further purification.

[0038] Add aniline (5 mmol) or various substituted anilines (5 mmol), sodium bicarbonate (6 mmol), and dichloromethane to a 50 mL reaction flask and stir for 10 minutes. Slowly drip the crude product 2,3-dibromopropionyl chloride with different substituents dissolved in dichloromethane (6 mmol) into the reaction system and react for 2 hours. After the reaction is complete, slowly add the TEM (6 mmol) solution to the reaction system. Stir at room temperature for 6 to 10 hours. After detecting the completion of the reaction by thin-layer chromatography (TLC), add water to the reaction system to quench the reaction, and then extract it with 3 × 30 mL of ethyl acetate. Combine the organic phases, dry, filter, and concentrate to obtain the crude product. The pure target compounds I-1, I-2, and I-3 are prepared according to the above similar method.

[0039] The application of α-bromoacrylamide compounds in the preparation of plant antifungal drugs or as a single active ingredient or in combination with other antibacterial drugs.

[0040] α-Bromoacrylamide compounds have significant inhibitory activity against the following plant pathogens:

[0041] Fusarium oxysporum f. sp. vasinfectum, Fusarium oxysporum f. sp. niveum, Fusarium coeruleum, Gibberella zeae, Alternaria solani, Alternaria brassicae, Alternaria alternata, Curvularia lunata, Colletotrichum gloeosporioides, Fusarium oxysporum f. sp. cucumerinum, Valsa mali, Magnaporthe oryzae, Physalospora piricola; Podosphaera xanthii; Plasmopara viticola.

[0042] The said drug has significant preventive and therapeutic effects on the following plant fungal diseases:

[0043] Fusarium wilt of watermelon, scab of wheat, early blight of tomato, black spot of Chinese cabbage, brown spot of tobacco, Curvularia leaf spot of maize, anthracnose of apple, Fusarium wilt of pumpkin, rice blast, ring rot of apple; powdery mildew of melon; downy mildew of grapevine.

[0044] The names, physical and chemical properties, and NMR spectral data of Compounds 1 - 45 are as follows:

[0045] 2 - Bromo - N - phenylacrylamide (A1 - 1). White powder, 70% yield, mp: 82.5–83.4 °C. 1 HNMR (400 MHz, chloroform - d) δ8.35 (s, 1H), 7.60–7.57 (m, 2H), 7.37 (dd, J = 8.6, 7.4 Hz, 2H), 7.21–7.15 (m, 1H), 7.14 (d, J = 1.7 Hz, 1H), 6.14 (d, J = 1.7 Hz, 1H).

[0046] 2 - Bromo - N - (2 - fluorophenyl)acrylamide (A1 - 2). Burgundy powder, 68% yield, mp: 45.5–46.0 °C. 1 HNMR (400 MHz, chloroform - d) δ8.67 (s, 1H), 8.33 (ddd, J = 8.9, 7.7, 1.5 Hz, 1H), 7.19–7.13 (m, 1H), 7.13 (d, J = 1.9 Hz, 2H), 7.11 (d, J = 1.1 Hz, 1H), 6.15 (d, J = 1.8 Hz, 1H). 13 CNMR (101 MHz, DMSO - d 6 ) δ161.3, 156.1 (d, J = 247.4 Hz), 127.9 (d, J = 7.8 Hz), 127.5, 127.3 (d, J = 1.5 Hz), 125.4 (d, J = 12.1 Hz), 124.86 (d, J = 3.6 Hz), 124.7, 116.3 (d, J = 19.8 Hz). HRMS (positive ESI) m / z: calcd for C 9 H 8 BrFNO + [M + H] + , 243.9768 ( 79 Br), 245.9747 ( 81 Br); found, 243.9767, 245.97456.

[0047] 2-Bromo-N-(3-fluorophenyl)acrylamide (A1-3). Brown powder, yield 74%, mp: 57.5–58.3 °C. 1 H NMR (400 MHz, chloroform-d) δ 8.37 (s, 1H), 7.55 (dt, J = 10.7, 2.3 Hz, 1H), 7.31 (td, J = 8.2, 6.3 Hz, 1H), 7.21 (ddd, J = 8.1, 2.0, 1.0 Hz, 1H), 7.13 (d, J = 1.8 Hz, 1H), 6.87 (td, J = 8.3, 2.5, 1.0 Hz, 1H), 6.15 (d, J = 1.8 Hz, 1H).

[0048] 2-Bromo-N-(4-fluorophenyl)acrylamide (A1-4). Brown powder, yield 67%, mp: 40.5–41.8 °C. 1 H NMR (400 MHz, chloroform-d) δ 8.33 (s, 1H), 7.59–7.51 (m, 2H), 7.13 (d, J = 1.7 Hz, 1H), 7.06 (d, J = 9.1, 8.2 Hz, 2H), 6.15 (d, J = 1.7 Hz, 1H).

[0049] 2-Bromo-N-(2-chlorophenyl)acrylamide (A1-5). Brown powder, yield 68%, mp: 80.5–81.4 °C. 1 H NMR (400 MHz, chloroform-d) δ 9.07 (s, 1H), 8.44 (dd, J = 8.3, 1.5 Hz, 1H), 7.41 (dd, J = 8.0, 1.5 Hz, 1H), 7.34–7.28 (m, 1H), 7.15 (d, J = 1.7 Hz, 1H), 7.10 (td, J = 7.8, 1.6 Hz, 1H), 6.18 (d, J = 1.7 Hz, 1H). 13 C NMR (101 MHz, DMSO-d 6 ) δ 161.0, 134.7, 130.1, 129.3, 128.2, 128.1, 127.9, 127.8, 124.6. HRMS (positive ESI) m / z: calcd for C 9 H 8 BrClNO + [M+H] + , 259.9472 ( 79 Br), 261.9452 ( 81Br); found, 259.9470, 261.9447.

[0050] 2-Bromo-N-(3-chlorophenyl)acrylamide (A1-6). Yellow powder in 67% yield, mp: 82.5–83.2 °C. 1 H NMR (400 MHz, chloroform-d) δ 8.34 (s, 1H), 7.71 (t, J = 2.1 Hz, 1H), 7.43 (ddd, J = 8.2, 2.1, 1.0 Hz, 1H), 7.29 (t, J = 8.1 Hz, 1H), 7.16 (dd, J = 2.0, 1.0 Hz, 1H), 7.14 (d, J = 1.8 Hz, 1H), 6.16 (d, J = 1.7 Hz, 1H).

[0051] 2-Bromo-N-(4-chlorophenyl)acrylamide (A1-7). Light yellow powder in 71% yield, mp: 82.5–83.2 °C. 1 H NMR (400 MHz, chloroform-d) δ 8.34 (s, 1H), 7.55 (d, J = 8.8 Hz, 2H), 7.34 (d, J = 8.8 Hz, 2H), 7.14 (d, J = 1.7 Hz, 1H), 6.16 (d, J = 1.7 Hz, 1H).

[0052] 2-Bromo-N-(2-bromophenyl)acrylamide (A1-8). Dark yellow powder in 69% yield, mp: 46.9–48.5 °C. 1 H NMR (400 MHz, chloroform-d) δ 9.07 (s, 1H), 8.42 (dd, J = 8.3, 1.6 Hz, 1H), 7.58 (dd, J = 8.1, 1.5 Hz, 1H), 7.39–7.33 (m, 1H), 7.16 (d, J = 1.7 Hz, 1H), 7.04 (ddd, J = 8.1, 7.4, 1.6 Hz, 1H), 6.18 (d, J = 1.8 Hz, 1H). 13 C NMR (101 MHz, DMSO-d 6 ) δ 161.0, 136.1, 128.7, 128.7, 128.2, 127.8, 124.6, 120.1. HRMS (positive ESI) m / z: calcd for C 9 H 8 Br 2 NO + [M + H] +,303.8967( 79 Br+ 79 Br),305.8947( 79 Br+ 81 Br),307.8926( 81 Br+ 81 Br); found, 303.8962, 305.8942, 307.8921.

[0053] 2-Bromo-N-(3-bromophenyl)acrylamide (A1-9). White powder in 70% yield, mp: 92.2–92.6 °C. 1 H NMR (400 MHz, chloroform-d) δ 8.33 (s, 1H), 7.85 (t, J = 2.0 Hz, 1H), 7.51–7.48 (m, 1H), 7.23 (t, J = 8.0 Hz, 1H), 7.14 (d, J = 1.7 Hz, 1H), 6.16 (d, J = 1.8 Hz, 1H).

[0054] 2-Bromo-N-(4-bromophenyl)acrylamide (A1-10). White powder in 73% yield, mp: 91.4–92.1 °C. 1 H NMR (400 MHz, chloroform-d) δ 8.34 (s, 1H), 7.49 (s, 4H), 7.13 (d, J = 1.7 Hz, 1H), 6.15 (d, J = 1.8 Hz, 1H).

[0055] 2-Bromo-N-(2-iodophenyl)acrylamide (A1-11). White powder in 72% yield, mp: 91.4–92.1 °C. 1 H NMR (400 MHz, chloroform-d) δ 8.93–8.76 (m, 1H), 8.32 (dd, J = 8.3, 1.5 Hz, 1H), 7.82 (dd, J = 8.0, 1.4 Hz, 1H), 7.39 (td, J = 8.4, 7.9, 1.4 Hz, 1H), 7.16 (d, J = 1.6 Hz, 1H), 6.90 (td, J = 7.7, 1.5 Hz, 1H), 6.19 (d, J = 1.7 Hz, 1H). 13 C NMR (101 MHz, DMSO-d 6 ) δ 161.0, 139.4, 139.4, 129.4, 129.0, 128.0, 127.6, 124.9, 98.2. HRMS (positive ESI) m / z: calcd for C9 H 8 BrINO + [M+H] + ,351.8828( 79 Br),353.8808( 81 Br); found, 351.8824, 353.8803.

[0056] 2-Bromo-N-(3-iodophenyl)acrylamide (A1-12). Light yellow powder, yield 71%, mp: 95.2–95.9 °C. 1 H NMR (400 MHz, chloroform-d) δ 8.35–8.24 (m, 1H), 7.99 (t, J = 1.9 Hz, 1H), 7.58–7.54 (m, 1H), 7.53–7.49 (m, 1H), 7.13 (d, J = 1.8 Hz, 1H), 7.09 (t, J = 8.0 Hz, 1H), 6.16 (d, J = 1.8 Hz, 1H).

[0057] 2-Bromo-N-(4-iodophenyl)acrylamide (A1-13). Yellow powder, yield 72%, 94.4–94.9 °C. 1 H NMR (400 MHz, chloroform-d) δ 8.33 (s, 1H), 7.67 (d, J = 8.7 Hz, 2H), 7.37 (d, J = 8.7 Hz, 2H), 7.13 (d, J = 1.7 Hz, 1H), 6.15 (d, J = 1.7 Hz, 1H).

[0058] 2-Bromo-N-(2-hydroxyphenyl)acrylamide (A1-14). Light yellow powder, yield 72%, mp: 139.3–140.1 °C. 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.15 (s, 1H), 9.29 (s, 1H), 7.86 (dd, J = 8.0, 1.6 Hz, 1H), 7.02 (dd, J = 7.6, 1.6 Hz, 1H), 6.91 (dd, J = 8.0, 1.7 Hz, 2H), 6.82 (td, J = 7.6, 1.5 Hz, 1H), 6.30 (d, J = 2.4 Hz, 1H).

[0059] 2-Bromo-N-(3-hydroxyphenyl)acrylamide (A1-15). Dark yellow powder, yield 69%, mp: 159.7–161.3 °C.1 1H NMR (400 MHz, DMSO-d 6 ) δ 10.09 (s, 1H), 9.42 (s, 1H), 7.16 (t, J = 2.2 Hz, 1H), 7.07 (t, J = 8.0 Hz, 1H), 6.99 (dt, J = 8.3, 1.3 Hz, 1H), 6.65 (d, J = 3.1 Hz, 1H), 6.50–6.45 (m, 1H), 6.23 (d, J = 3.1 Hz, 1H).

[0060] 2-Bromo-N-(4-hydroxyphenyl)acrylamide (A1-16). Light yellow powder, 70% yield, mp: 118.7–119.3 °C. 1 1H NMR (400 MHz, DMSO-d 6 ) δ 9.95 (s, 1H), 9.28 (s, 1H), 7.34 (s, 2H), 6.67 (d, J = 8.9 Hz, 2H), 6.63 (d, J = 3.0 Hz, 1H), 6.18 (d, J = 3.0 Hz, 1H).

[0061] 2-Bromo-N-(2-trifluoromethylphenyl)acrylamide (A1-17). Light yellow liquid, 70% yield. 1 1H NMR (400 MHz, chloroform-d) δ 8.86 (s, 1H), 8.28 (s, 1H), 7.68–7.57 (m, 2H), 7.30 (d, J = 7.9 Hz, 1H), 7.16 (d, J = 1.7 Hz, 1H), 6.19 (d, J = 1.7 Hz, 1H). HRMS (positive ESI) m / z: calcd for C 10 H 8 BrF 3 NO + [M + H] + , 293.9736 ( 79 Br), 295.9715 ( 81 Br); found, 293.9732, 295.9712.

[0062] 2-Bromo-N-(3-trifluoromethylphenyl)acrylamide (A1-18). Light yellow liquid, 73% yield. 11H NMR (400 MHz, chloroform-d) δ 8.45 (s, 1H), 7.90 (s, 1H), 7.79 (dt, J = 7.9, 1.6 Hz, 1H), 7.50 (t, J = 8.0 Hz, 1H), 7.44 (d, J = 7.8 Hz, 1H), 7.16 (d, J = 1.8 Hz, 1H), 6.19 (d, J = 1.8 Hz, 1H).

[0063] 2-Bromo-N-(2-cyanophenyl)acrylamide (A1-19). White powder, yield 69%, mp: 89.1–90.1 °C. 1 1H NMR (400 MHz, chloroform-d) δ 9.03 (s, 1H), 8.50–8.44 (m, 1H), 7.67–7.62 (m, 2H), 7.24 (dd, J = 7.6, 1.0 Hz, 1H), 7.18 (d, J = 1.8 Hz, 1H), 6.23 (d, J = 1.8 Hz, 1H); 13 13C NMR (101 MHz, chloroform-d) δ 159.0, 139.9, 134.2, 132.4, 129.9, 125.0, 121.9, 120.7, 116.0, 102.8. HRMS (positive ESI) m / z: calcd for C 10 H 8 BrN 2 O + [M + H] + , 250.9815 ( 79 Br), 252.9794 ( 81 Br); found, 250.9811, 252.9790.

[0064] 2-Bromo-N-(3-cyanophenyl)acrylamide (A1-20). White powder, yield 70%, mp: 91.4–92.1 °C. 1 1H NMR (400 MHz, chloroform-d) δ 8.45 (s, 1H), 8.03 (d, J = 1.5 Hz, 1H), 7.76 (dt, J = 7.1, 2.3 Hz, 1H), 7.50–7.44 (m, 2H), 7.16 (d, J = 1.8 Hz, 1H), 6.19 (d, J = 1.8 Hz, 1H).

[0065] 2-Bromo-N-(4-cyanophenyl)acrylamide (A1-21). White powder, yield 72%, mp: 92.4–93.1 °C.1 1H NMR (400 MHz, chloroform-d) δ 8.52 (s, 1H), 7.74 (d, J = 8.8 Hz, 2H), 7.66 (d, J = 8.8 Hz, 2H), 7.15 (d, J = 1.8 Hz, 1H), 6.20 (d, J = 1.8 Hz, 1H). 13 13C NMR (101 MHz, DMSO-d 6 ) δ 162.1, 143.1, 133.7, 127.4, 124.8, 120.8, 119.4, 106.5. HRMS (positive ESI) m / z: calcd for C 10 H 8 BrN 2 O + [M + H] + , 250.9815 ( 79 Br), 252.9794 ( 81 Br); found, 250.9811, 252.9795.

[0066] 2-Bromo-N-(2-methoxyphenyl)acrylamide (A1-22). Dark yellow liquid in 67% yield, 1 1H NMR (400 MHz, chloroform-d) δ 9.13 (s, 1H), 8.40 (dd, J = 8.0, 1.6 Hz, 1H), 7.13–7.08 (m, 2H), 6.99 (td, J = 7.8, 1.4 Hz, 1H), 6.91 (dd, J = 8.1, 1.4 Hz, 1H), 6.12 (d, J = 1.6 Hz, 1H), 3.93 (s, 3H). 13 13C NMR (101 MHz, DMSO-d 6 ) δ 159.7, 150.6, 128.1, 126.6, 126.2, 124.2, 122.3, 120.9, 111.7, 56.4. HRMS (positive ESI) m / z: calcd for C 10 H 11 BrNO 2 + [M + H] + , 255.9968 ( 79 Br), 257.9947 ( 81 Br); found, 255.9966, 257.9941.

[0067] 2-Bromo-N-(3-methoxyphenyl)acrylamide (A1-23). Dark yellow liquid, yield 69%, 1H NMR (400 MHz, chloroform-d) δ 8.33 (s, 1H), 7.35 (t, J = 2.3 Hz, 1H), 7.24 (dd, J = 8.0 Hz, 1H), 7.12 (d, J = 1.6 Hz, 1H), 7.04 (dd, J = 8.1, 2.0 Hz, 1H), 6.73 (dd, J = 8.3, 2.5 Hz, 1H), 6.14 (d, J = 1.6 Hz, 1H), 3.82 (s, 3H).

[0068] 2-Bromo-N-(o-tolyl)acrylamide (A1-24). Brown liquid, yield 70%. 1 1H NMR (400 MHz, chloroform-d) δ 8.35 (s, 1H), 7.97 (d, J = 8.0 Hz, 1H), 7.25 (d, J = 3.4 Hz, 1H), 7.23–7.19 (m, 1H), 7.14 (d, J = 1.9 Hz, 1H), 7.09 (d, J = 1.3 Hz, 1H), 6.14 (d, J = 1.6 Hz, 1H), 2.32 (s, 3H). 13 13C NMR (101 MHz, chloroform-d) δ 161.4, 158.9, 132.5 (d, J = 8.80 Hz), 131.1 (d, J = 3.30 Hz), 128.5, 124.5 (d, J = 9.90 Hz), 122.8, 117.13 (d, J = 24.2 Hz), 113.28 (d, J = 24.2 Hz), 17.7.

[0069] 2-Bromo-N-(m-tolyl)acrylamide (A1-25). White powder, yield 72%, mp: 72.6–73.4 °C. 1 1H NMR (400 MHz, chloroform-d) δ 8.35–8.26 (m, 1H), 7.42 (s, 1H), 7.39–7.35 (m, 1H), 7.24 (t, J = 7.6 Hz, 1H), 7.12 (d, J = 1.7 Hz, 1H), 6.99 (dd, J = 7.4, 1.5 Hz, 1H), 6.13 (d, J = 1.7 Hz, 1H), 2.36 (s, 3H).

[0070] 2-Bromo-N-(p-tolyl)acrylamide (A1-26). Light brown solid in 74% yield, 72.1–72.5 °C, mp: 72.11 - 72.5 °C. 1 H NMR (400 MHz, chloroform-d) δ 8.30 (s, 1H), 7.46 (d, J = 8.4 Hz, 2H), 7.17 (d, J = 8.2 Hz, 2H), 7.12 (s, 1H), 6.13 (d, J = 1.6 Hz, 1H), 2.34 (s, 3H).

[0071] 2-Bromo-N-(2-nitrophenyl)acrylamide (A1-27). Dark yellow solid in 66% yield, 1 H NMR (400 MHz, chloroform-d) δ 11.51 (s, 1H), 8.83 (d, J = 8.5 Hz, 1H), 8.29–8.25 (m, 1H), 7.71 (ddd, J = 8.6, 7.2, 1.6 Hz, 1H), 7.28 (t, J = 8.8, 1H), 7.16 (d, J = 1.7 Hz, 1H), 6.24 (d, J = 1.8 Hz, 1H). 13 C NMR (101 MHz, DMSO-d 6 ) δ 161.0, 142.3, 134.9, 131.6, 128.9, 126.5, 125.8, 125.7, 124.0. HRMS (positive ESI) m / z: calcd for C 9 H 8 BrN 2 O 3 + [M + H] + , 270.9713 ( 79 Br), 272.9692 ( 81 Br); found, 270.9714, 272.9690.

[0072] 2-Bromo-N-(3-nitrophenyl)acrylamide (A1-28). Yellow solid in 65% yield, 1 H NMR (400 MHz, Chloroform-d) δ 8.55 (s, 1H), 8.49 (t, J = 2.2 Hz, 1H), 8.10–7.96 (m, 2H), 7.56 (t, J = 8.2 Hz, 1H), 7.19 (d, J = 1.8 Hz, 1H), 6.22 (d, J = 1.8 Hz, 1H).

[0073] 2-Bromo-N-(4-nitrophenyl)acrylamide (A1-29). White powder, yield 72%, mp: 90.4–91.1 °C. 1 H NMR (400 MHz, chloroform-d) δ 8.61 (s, 1H), 8.27 (d, J = 9.2 Hz, 2H), 7.80 (d, J = 9.2 Hz, 2H), 7.19 (d, J = 1.9 Hz, 1H), 6.23 (d, J = 1.9 Hz, 1H).

[0074] 2-Bromo-N-(2-isopropylphenyl)acrylamide (A1-30). Dark yellow solid, yield 67%, 1 H NMR (400 MHz, chloroform-d) δ 8.43 (s, 1H), 7.88 (d, J = 7.6 Hz, 1H), 7.32 (dd, J = 7.4, 2.0 Hz, 1H), 7.23 (ddd, J = 9.0, 7.4, 1.9 Hz, 2H), 7.15 (d, J = 1.7 Hz, 1H), 6.15 (d, J = 1.7 Hz, 1H), 3.05 (p, J = 6.8 Hz, 1H), 1.30 (d, J = 6.8 Hz, 6H). 13 C NMR (101 MHz, Chloroform-d) δ 158.9, 139.8, 133.7, 128.6, 126.6, 126.4, 125.7, 123.4, 123.1, 28.2, 22.9. HRMS (positive ESI) m / z: calcd for C 12 H 15 BrNO + [M+H] + , 268.0332 ( 79 Br), 270.0311 ( 81 Br); found, 268.0330, 270.0308.

[0075] 2-Bromo-N-(3-isopropylphenyl)acrylamide (A1-31). Dark yellow solid, yield 66%, 11H NMR (400 MHz, chloroform-d) δ 8.37–8.28 (m, 1H), 7.45–7.39 (m, 2H), 7.29 (t, J = 7.8 Hz, 1H), 7.13 (d, J = 1.7 Hz, 1H), 7.05 (dt, J = 7.5, 1.3 Hz, 1H), 6.13 (d, J = 1.7 Hz, 1H), 2.92 (p, J = 6.9 Hz, 1H), 1.26 (d, J = 6.9 Hz, 6H). 13 13C NMR (101 MHz, Chloroform-d) δ 158.9, 150.1, 137.0, 129.0, 128.3, 123.5, 123.1, 118.4, 117.9, 34.2, 23.9. HRMS (positive ESI) m / z: calcd for C 12 11 15 7 + BrNO + [M + H] 79 , 268.0332 ( 81 79

[0076] 2-Bromo-N-(4-tert-butylphenyl)acrylamide (A1-32). Dark yellow solid in 65% yield, 1 1H NMR (400 MHz, chloroform-d) δ 8.31 (s, 1H), 7.50 (d, J = 8.6 Hz, 2H), 7.38 (d, J = 8.6 Hz, 2H), 7.12 (d, J = 1.6 Hz, 1H), 6.12 (d, J = 1.6 Hz, 1H), 1.31 (s, 9H).

[0077] 2-Bromo-N-(2,3-dimethylphenyl)acrylamide (A1-33). Yellow powder in 70% yield, mp: 80.4–81 °C. 1 1H NMR (400 MHz, chloroform-d) δ 8.32 (s, 1H), 7.66 (d, J = 8.0 Hz, 1H), 7.17–7.12 (m, 2H), 7.05 (d, J = 7.5 Hz, 1H), 6.14 (d, J = 1.7 Hz, 1H), 2.32 (s, 3H), 2.20 (s, 3H). 13CNMR (101 MHz, chloroform-d) δ 159.0, 137.5, 134.9, 128.9, 128.3, 127.8, 126.0, 123.2, 121.2, 20.6, 13.7. HRMS (positive ESI) m / z: calcd for C 11 H 13 BrNO + [M + H] + , 254.0175( 79 Br), 256.0155( 81 Br); found, 254.0171, 256.0149.

[0078] 2-Bromo-N-(2,5-dimethylphenyl)acrylamide (A1-34). White powder in 73% yield, mp: 92.6–93.1 °C. 1 H NMR (400 MHz, Chloroform-d) δ 8.31 (s, 1H), 7.81 (d, J = 1.7 Hz, 1H), 7.14 (d, J = 1.7 Hz, 1H), 7.09 (d, J = 7.7 Hz, 1H), 6.95–6.90 (m, 1H), 6.14 (d, J = 1.7 Hz, 1H), 2.33 (s, 3H), 2.27 (s, 3H). 13 C NMR (101 MHz, chloroform-d) δ 158.6, 136.6, 135.0, 130.3, 128.4, 126.4, 125.8, 123.2, 122.7, 21.2, 17.2. HRMS (positive ESI) m / z: calcd for C 11 H 13 BrNO + [M + H] + , 254.0175( 79 Br), 256.0155( 81 Br); found, 254.0172, 256.0149.

[0079] 2-Bromo-N-(2,6-dimethylphenyl)acrylamide (A1-35). White crystal in 71% yield, mp: 94.8–96.1 °C. 1 H NMR (500 MHz, DMSO-d 6)δ8.92 (singlet, 1H), 7.36 (triplet, J = 7.5 Hz, 2H), 7.32–7.26 (multiplet, 3H), 6.73 (doublet, J = 2.6 Hz, 1H), 6.20 (doublet, J = 2.5 Hz, 1H), 4.38 (doublet, J = 6.1 Hz, 2H). 13 C NMR (101 MHz, chloroform-d) δ159.4, 135.4, 133.3, 128.3, 128.2, 127.8, 122.6, 18.4. HRMS (positive ESI) m / z: calculated for C 11 H 13 BrNO + [M + H] + , 254.0175 ( 79 Br), 256.0155 ( 81 Br); found, 254.0171, 256.0148.

[0080] 2-Bromo-N-(3,4-dimethylphenyl)acrylamide (A1-36). White powder in 74% yield, mp: 94.7–96.3 °C. 1H NMR (400 MHz, chloroform-d) δ8.31–8.20 (multiplet, 1H), 7.36 (doublet, J = 2.3 Hz, 1H), 7.30 (doublet of doublets, J = 8.1, 2.3 Hz, 1H), 7.14–7.09 (multiplet, 2H), 6.11 (doublet, J = 1.6 Hz, 1H), 2.25 (doublet, J = 9.8 Hz, 6H). HRMS (positive ESI) m / z: calculated for C11H13BrNO+ [M + H]+, 254.0175 (79Br), 256.0155 (81Br); found, 254.0171, 256.0149.

[0081] 2-Bromo-N-(3,5-dimethylphenyl)acrylamide (A1-37). Brown powder in 72% yield, mp: 93.2–94 °C. 1 1H NMR (400 MHz, chloroform-d) δ8.27 (singlet, 1H), 7.22 (singlet, 2H), 7.12 (doublet, J = 1.7 Hz, 1H), 6.83–6.80 (multiplet, 1H), 6.12 (doublet, J = 1.6 Hz, 1H), 2.32 (singlet, 6H), 1313C NMR (101 MHz, chloroform-d) δ 158.8, 138.8, 136.8, 128.2, 127.0, 123.0, 118.0, 21.4. HRMS (positive ESI) m / z: calcd for C 11 H 13 BrNO + [M + H] + , 254.0175 ( 79 Br), 256.0155 ( 81 Br); found, 254.0170, 256.0148.

[0082] 2-Bromo-N-(3,5-dibromophenyl)acrylamide (A1-38). White powder in 71% yield, mp: 87.2–88.2 °C. 1 1H NMR (400 MHz, chloroform-d) δ 8.33 (s, 1H), 7.76 (d, J = 1.7 Hz, 2H), 7.47 (t, J = 1.7 Hz, 1H), 7.14 (d, J = 1.8 Hz, 1H), 6.18 (s, 1H). 13 13C NMR (101 MHz, chloroform-d) δ 159.1, 139.0, 130.6, 129.5, 123.1, 122.0, 121.9. HRMS (positive ESI) m / z: calcd for C 9 H 7 Br 3 NO + [M + H] + , 383.8052 ( 79 Br+ 79 Br+ 81 Br), 385.8031 ( 79 Br+ 81 Br+ 81 Br); found, 383.8051, 385.8023.

[0083] 2-Bromo-N-(4-fluoro-2-methylphenyl)acrylamide (A1-39). White powder in 74% yield, mp: 70.3–70.6 °C. 11H NMR (400 MHz, chloroform-d) δ 8.24 (s, 1H), 7.84 (dd, J = 9.7, 5.3 Hz, 1H), 7.14 (d, J = 1.7 Hz, 1H), 6.97–6.92 (m, 2H), 6.15 (d, J = 1.7 Hz, 1H), 2.31 (s, 3H). 13 13C NMR (101 MHz, chloroform-d) δ 161.4, 159.0, 132.5 (d, J = 8.0 Hz), 131.1 (d, J = 2.8 Hz), 128.5, 124.5 (d, J = 8.5 Hz), 122.8, 117.1 (d, J = 22.6 Hz), 113.3 (d, J = 22.1 Hz), 17.7. HRMS (positive ESI) m / z: calcd for C 10 H 10 BrFNO + [M + H] + , 257.9924 ( 79 Br), 259.9904 ( 81 Br); found, 257.9920, 259.9900.

[0084] 2-Bromo-N-(2-fluoro-4-methylphenyl)acrylamide (A1-40). White powder in 72% yield, mp: 44.2–44.7 °C. 1 1H NMR (400 MHz, chloroform-d) δ 8.59 (s, 1H), 8.17 (t, J = 8.4 Hz, 1H), 7.12 (d, J = 1.7 Hz, 1H), 6.98–6.92 (m, 2H), 6.14 (d, J = 1.6 Hz, 1H), 2.33 (s, 3H). 13 13C NMR (101 MHz, Chloroform-d) δ 158.5, 152.8 (d, J = 244.3 Hz), 135.9 (d, J = 7.3 Hz), 128.6, 125.0 (d, J = 3.2 Hz), 122.9 (d, J = 10.3 Hz), 122.5, 121.3 (d, J = 1.2 Hz), 115.5 (d, J = 18.8 Hz), 20.9. HRMS (positive ESI) m / z: calcd for C 10 H 10 BrFNO + [M + H] + , 257.9924 ( 79 Br), 259.9904 ( 81Br); found, 257.9921, 259.9901.

[0085] N-Benzyl-2-bromoacrylamide (A2-1). Colourless liquid in 65% yield, 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.92 (s, 1H), 7.36 (t, J = 7.5 Hz, 2H), 7.32–7.26 (m, 3H), 6.73 (d, J = 2.6 Hz, 1H), 6.20 (d, J = 2.5 Hz, 1H), 4.38 (d, J = 6.1 Hz, 2H).

[0086] 2-Bromo-N-phenethylacrylamide (A2-2). Colourless liquid in 67% yield, 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.41 (s, 1H), 7.32 (dd, J = 8.1, 6.9 Hz, 2H), 7.24 (d, J = 6.6 Hz, 3H), 6.65 (d, J = 2.5 Hz, 1H), 6.14 (d, J = 2.4 Hz, 1H), 3.43–3.38 (m, 2H), 2.81 (t, J = 7.5 Hz, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 161.02, 141.12, 128.58, 128.38, 127.39, 126.16, 123.03, 40.21, 33.24, 30.76. HRMS (positive ESI) m / z: calcd for C 11 H 13 BrNO + [M + H] + , 254.0175 ( 79 Br), 256.0155 ( 81 Br); found, 254.0172, 256.0150.

[0087] 2-Bromo-N-(3-phenylpropyl)acrylamide (A2-3). Colourless liquid in 68% yield, 1 H NMR (400 MHz, DMSO-d 6)δ8.37(s,1H),7.28(t,J=7.4Hz,2H),7.22–7.15(m,3H),6.64(d,J=2.4Hz,1H),6.12(d,J=2.5Hz,1H),3.17(td,J=7.2,5.8Hz,2H),2.58(t,J=7.7Hz,2H),1.83–1.72(m,2H). 13 C NMR(101MHz,Chloroform-d)δ160.94,138.44,128.79,128.77,127.46,126.73,122.97,41.78,35.40.HRMS(positive ESI)m / z:calcd for C 12 H 15 BrNO + [M+H] + ,268.0332( 79 Br),270.0311( 81 Br);found,268.0329,270.0306.

[0088] Application Example 1 - Determination of the in vitro antibacterial activity of the compound

[0089] The antibacterial activity was determined by the hyphal linear growth rate method.

[0090] The test bacteria were: Fusarium oxysporum f. sp. vasinfectum, Fusarium oxysporum f. sp. niveum, Fusarium coeruleum, Gibberella zeae, Alternaria solani, Alternaria brassicae, Alternaria alternata, Curvularia lunata, Colletotrichum gloeosporioides, Fusarium oxysporum f. sp. cucumerinum, Valsa mali, Magnaporthe oryzae, Physalospora piricola. The medium was PDA. The test solution of the compound of the present invention was prepared with 5% DMSO aqueous solution (v / v). The concentration of the test compound in the medium was 75 μg / mL. The positive control drugs were thiabendazole and kresoxim-methyl (purity > 98%), and the preparation method was the same as that of the compound of the present invention. Each test was set with three parallels each time and repeated three times. The measurement results were expressed as the average inhibition rate.

[0091] Application Example 2

[0092] (1) Pot experiment of the compound against downy mildew

[0093] The compound of the present invention was added to dimethyl sulfoxide containing 10% OP-10 to prepare a solution with a concentration of 160 mg / mL. The preparation methods of the compound of the invention and the positive drug were the same. Before the experiment, it was diluted with water to 300 μg / mL, and then the test leaves were sprayed. The test fungus was Plasmopara viticola. The experiment was carried out by the spore germination method on leaves. A spore suspension of Plasmopara viticola with a spore concentration of 105 spores / mL was inoculated on the back of grape leaves by spraying. The inoculated plants were first placed at room temperature in an isolation chamber with high humidity for 24 h, then transferred to a greenhouse with environmental humidity and placed at room temperature for 48 h. Finally, the plants were transferred to a high-humidity environment and placed for 24 h. Then, the plants were moved to the natural environment. After the moisture on the plant surface had naturally evaporated, the infected leaves were removed from the plants and sprayed with the test solution at 300 μg / mL. After the moisture on the liquid surface had naturally evaporated, the petioles of the leaves were immersed in water, and then they were placed in a high-humidity environment for 72 h. The test effect was evaluated by comparing the percentage of the spore coverage area on the leaf surfaces of the experimental group and the control group.

[0094] (2) Pot experiment against powdery mildew

[0095] The test compound was added to dimethyl sulfoxide containing 10% OP-10 to prepare a solution with a concentration of 160 mg / mL. The preparation methods of the compound of the invention and the positive drug were the same. Before the experiment, it was diluted with water to 300 μg / mL, and then the test leaves were sprayed. The test fungus was Plasmopara viticola. The experiment was carried out by the spore germination method on leaves. A spore suspension of Plasmopara viticola with a spore concentration of 105 spores / mL was inoculated on the back of grape leaves by spraying. The number of melon seedlings used in each experiment was about 30, and the melon seedlings grew in sterilized compost. The melon plants inoculated with the powdery mildew spore suspension of melon were placed in a high-humidity environment for 24 h, and then sprayed with the test solution at 500 μg / mL. Five days later, the antibacterial effect was evaluated by the same method as the above-mentioned pot antibacterial experiment against downy mildew.

[0096] The inhibitory activities of the compounds against plant pathogenic bacteria are shown in Table 1 and Table 2, and the control indexes of the compounds against powdery mildew of melon and downy mildew of grape are shown in Table 3.

[0097] Table 1 Inhibitory activities of compounds against plant pathogenic fungi

[0098]

[0099]

[0100] Table 2 Inhibitory activities of compounds against plant pathogenic fungi

[0101]

[0102] Table 3. Control indices of compounds against powdery mildew of melon and downy mildew of grape

[0103]

[0104]

[0105] As can be seen from Tables 1 - 3: at a concentration of 75 μg / mL, most of the compounds showed highly efficient and broad-spectrum inhibitory activities against all tested plant pathogens. At a concentration of 300 ppm, all the tested compounds had significant control effects against downy mildew of grape and powdery mildew of melon, and had potential uses for preparing plant antibacterial drugs, and could be used as active ingredients or synergistic ingredients of plant antibacterial drugs.

[0106] Although the above embodiments have described the present invention in detail, they are only a part of the embodiments of the present invention, rather than all embodiments. Other embodiments can also be obtained based on these embodiments without creative efforts, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A class of α-bromoacrylamide compounds, characterized in that: The structural formula is: in: Compound A1: R is ortho-fluorine, chlorine, bromine, iodine, trifluoromethyl, cyano, methoxy, nitro, isopropyl, 3-isopropyl, 4-cyano, 2,3-dimethyl, 2,5-dimethyl, 2,6-dimethyl, 3,5-dimethyl, 3,5-dibromo, 2-methyl, 4-fluoro, 2-fluoro, 4-methyl; A2 compound: The carbon number n is 2 and 3 respectively.

2. A class of α-bromoacrylamide compounds with excellent antibacterial activity, characterized in that: The structural formula is: Compound A1: R is methyl, nitro, hydroxyl, cyano, isopropyl, fluorine, chlorine, bromine, iodine in the ortho, para or meta position; 2,3-dimethyl, 2,5-dimethyl, 2,6-dimethyl, 3,4-dimethyl, 3,5-dimethyl, 3,5-dibromo; 2-methyl, 4-fluoro, 2-fluoro, 4-methyl, 2-methoxy, 3-methoxy, 2-trifluoromethyl, 3-trifluoromethyl; A2 compound: The carbon number n is 1, 2, and 3 respectively.

3. The use of α-bromoacrylamide compounds as claimed in claim 2, characterized in that: The α-bromoacrylamide compound is used in the preparation of plant antifungal drugs.

4. The use of α-bromoacrylamide compounds as claimed in claim 2, characterized in that: The α-bromoacrylamide compound can be used as a single effective ingredient or in combination with other antibacterial drugs in the preparation of plant antifungal drugs.

5. The use of α-bromoacrylamide compounds as claimed in claim 3 or 4, characterized in that: The α-bromoacrylamide compounds have significant inhibitory activity against the following plant pathogens: Cotton wilt pathogens, watermelon wilt pathogens, potato dry rot pathogens, wheat fusarium rust pathogens, tomato early blight pathogens, cabbage black spot pathogens, tobacco brown spot pathogens, corn curvature pathogens, apple anthracnose pathogens, pumpkin wilt pathogens, apple rot pathogens, rice blast pathogens, apple ring rot pathogens; melon powdery mildew pathogens; grape downy mildew pathogens.

6. The use of α-bromoacrylamide antibacterial drugs as claimed in claim 3 or 4, characterized in that: The drug has significant effects in preventing or treating the following plant fungal diseases: Watermelon wilt, wheat ergot, tomato early blight, cabbage black spot, tobacco brown spot, corn curvature, apple anthracnose, pumpkin wilt, rice blast, apple ring rot; melon powdery mildew; grape downy mildew.

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