Triazole derivatives of 2,4-dihydroxy-5-methyl-acetophenone and their use

Abstract

The application discloses a triazole derivative of 2,4-dihydroxy-5-methyl-acetophenone and application thereof, and the derivative has a compound with the structure shown in the following general formula or a pharmaceutically acceptable salt thereof; acetophenone A has excellent insecticidal activity; and the acetophenone A triazole derivative has excellent fungicidal activity and insecticidal activity.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of natural product pesticides, and relates to a triazole derivative of 2,4-dihydroxy-5-methyl-acetophenone and application thereof, in particular to an acetophenone A triazole derivative and application thereof to preparation of a fungicide and / or an insecticide. BACKGROUND

[0002] The natural product acetophenone A, full name 2,4-dihydroxy-5-methyl-acetophenone, is a fungal source polyketide metabolite, which has multiple biological activities, such as anti-plant pathogenic fungi, anticancer, antioxidant activity, etc. (Patent, application number: CN201410177356.2, CN201910450601.5; Bioorganic & Medicinal Chemistry, 26 (2018), 386-39.)

[0003] Triazole is an important heterocyclic ring and widely exists in different bioactive molecules. At the same time, triazole compounds also have many other advantages, such as good stability, high internal absorption rate and low cytotoxicity. Due to the important significance of triazole, it has attracted widespread attention of medicinal chemists and is widely used in the design of new biological and medical preparations. SUMMARY

[0004] The purpose of the application is to provide a triazole derivative of 2,4-dihydroxy-5-methyl-acetophenone and application thereof. The acetophenone A triazole derivative is a new type of compound, which shows good plant pathogenic fungus activity and insecticidal activity.

[0005] To achieve the above purpose, the technical scheme adopted by the application includes:

[0006] A triazole derivative of 2,4-dihydroxy-5-methyl-acetophenone, wherein the derivative has a compound with the structure shown in the general formula I or a pharmaceutically acceptable salt thereof.

[0007]

[0008] In the formula I and the formula II, R 1 is selected from one of methyl, isopropyl, cyclopropyl, isobutyl, sec-butyl and halogen;

[0009] In the formula I and the formula II, R 2one of C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, substituted or unsubstituted phenyl, substituted or unsubstituted benzyl, nitrogen-containing heterocycle containing 2-10 carbon atoms, oxygen-containing heterocycle containing 2-10 carbon atoms, sulfur-containing heterocycle containing 2-10 carbon atoms, nitrogen-containing heterocycle containing 2-10 carbon atoms substituted methyl, oxygen-containing heterocycle containing 2-10 carbon atoms substituted methyl, sulfur-containing heterocycle containing 2-10 carbon atoms substituted methyl, and the aforementioned acyl of different substitution;

[0010] each of the substituents of the substituted phenyl and substituted benzyl is independently selected from one or two or more of hydroxyl, halogen, cyano, nitro, trifluoromethyl, trifluoromethoxy, C1-C6 hydrocarbon group, C1-C6 alkoxy, C1-C6 alkylamino, dioxymethylene, and dioxyethylene;

[0011] R in Formula I and Formula II 1 R in Formula I and Formula II 2 one of substituted or unsubstituted phenyl, substituted or unsubstituted benzyl, nitrogen-containing heterocycle containing 2-10 carbon atoms, oxygen-containing heterocycle containing 2-10 carbon atoms, sulfur-containing heterocycle containing 2-10 carbon atoms, nitrogen-containing heterocycle containing 2-10 carbon atoms substituted methyl, oxygen-containing heterocycle containing 2-10 carbon atoms substituted methyl, sulfur-containing heterocycle containing 2-10 carbon atoms substituted methyl, and the aforementioned acyl of different substitution; each of the substituents of the substituted phenyl and substituted benzyl is independently selected from one or two or more of hydroxyl, halogen, cyano, nitro, trifluoromethyl, trifluoromethoxy, C1-C6 hydrocarbon group, C1-C6 alkoxy, C1-C6 alkylamino, dioxymethylene, and dioxyethylene.

[0012] Optionally, the derivative is one of the compounds shown in the following formulae:

[0013]

[0014]

[0015]

[0016] A triazole derivative of 2,4-dihydroxy-5-methyl-acetophenone, the derivative having a compound of the structure shown in the following general formula or a pharmaceutically acceptable salt thereof:

[0017]

[0018] wherein R in Formula III and IV 1 one of methyl, isopropyl, cyclopropyl, isobutyl, sec-butyl, and halogen;

[0019] R 2 one or two or more selected from the group consisting of hydrogen, hydroxyl, halogen, cyano, nitro, trifluoromethyl, trifluoromethoxy, C1-C6 alkyl, C1-C6 alkylamino, dioxymethylene and dioxyethylene.

[0020] The triazole derivative of 2,4-dihydroxy-5-methyl-acetophenone according to any one of the present application and 2,4-dihydroxy-5-methyl-acetophenone are used for preparing an insecticide.

[0021] Optionally, the insecticide is used for preventing and treating at least one of aphid, armyworm, diamondback moth and cotton bollworm.

[0022] The triazole derivative of 2,4-dihydroxy-5-methyl-acetophenone according to any one of the present application is used for preparing a fungicide.

[0023] Optionally, the fungicide is used for preventing and treating at least one of F. solani, Cytospora sp., C. gloeosporioides, B. cinerea, F. graminearum and M. grisea.

[0024] The advantages of the present application include:

[0025] The present application firstly discovers that natural product acetophenone A has good insecticidal activity, and on this basis, provides a preparation method of acetophenone A triazole derivative and application thereof in preventing and treating plant pathogenic fungi and insecticides. The acetophenone A triazole derivative of the present application shows good plant pathogenic fungi activity and insecticidal activity.

[0026] The compound of the general formula of the present application can be directly used as an insecticide and fungicide, or can be used with an agriculturally acceptable carrier, or can be used in combination with other insecticides and fungicides such as pyriminostm, bromothionate, ethyl mite, azocane and the like. Some of these combinations show synergistic effect, and some show additive effect. DETAILED DESCRIPTION

[0027] The technical solutions of the present application will be described clearly and completely below in combination with the embodiments of the present application. Obviously, the described embodiments are only some of the embodiments of the present application, but not all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application.

[0028] The acetophenone A and its triazole derivatives of the present application are compounds having the structure shown in the following general formula I or pharmaceutically acceptable salts thereof:

[0029]

[0030] The acetophenone A triazole derivatives of the present application are compounds having the structure shown in the following general formula III and IV or pharmaceutically acceptable salts thereof:

[0031]

[0032] wherein, R 1 is selected from hydrogen, methyl, isopropyl, cyclopropyl, isobutyl, sec-butyl and halogen; R 2 is selected from C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, substituted or unsubstituted phenyl, substituted or unsubstituted benzyl, nitrogen-containing heterocycle containing 2-10 carbon atoms, oxygen-containing heterocycle containing 2-10 carbon atoms, sulfur-containing heterocycle containing 2-10 carbon atoms, nitrogen-containing heterocycle containing 2-10 carbon atoms substituted methyl, oxygen-containing heterocycle containing 2-10 carbon atoms substituted methyl, sulfur-containing heterocycle containing 2-10 carbon atoms substituted methyl and acyl of different substitution of the foregoing; the substituents of the substituted phenyl and substituted benzyl are each independently selected from one or more of hydroxyl, halogen, cyano, nitro, trifluoromethyl, trifluoromethoxy, C1-C6 hydrocarbon group, C1-C6 alkoxy, C1-C6 alkylamino, dioxymethylene and dioxyethylene.

[0033] In the present application, specific examples of C1-C10 alkyl can be, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, etc.

[0034] C1-C6 hydrocarbon group can be selected from the specific examples of alkyl described above and satisfy the corresponding limitation.

[0035] C1-C6 alkylamino can be alkylamino formed from the specific examples of alkyl satisfying 1-6 carbon atoms described above.

[0036] C1-C6 alkoxy can be alkoxy formed from the specific examples of alkyl satisfying 1-6 carbon atoms described above.

[0037] The nitrogen-containing heterocycle having 2 to 10 carbon atoms can be an unsaturated nitrogen-containing heterocycle or a saturated nitrogen-containing heterocycle, as long as the ring structure of the heterocycle has nitrogen as a structural atom and the number of carbon atoms in the heterocycle is 2 to 10. For example, it can be unsubstituted or C1-C6 alkyl-substituted pyrrole, unsubstituted or C1-C6 alkyl-substituted pyrroline, unsubstituted or C1-C7 alkyl-substituted imidazole, unsubstituted or C1-C7 alkyl-substituted imidazoline, unsubstituted or C1-C5 alkyl-substituted pyridine, unsubstituted or C1-C5 alkyl-substituted pyridine, unsubstituted or C1-C7 alkyl-substituted pyrazole, unsubstituted or C1-C7 alkyl-substituted pyrazoline, unsubstituted or C1-C7 alkyl-substituted thiazole, unsubstituted or C1-C7 alkyl-substituted thiazoline, unsubstituted or C1-C7 alkyl-substituted oxazole, unsubstituted or C1-C7 alkyl-substituted oxazoline, and the like. The alkyl group as a substituent can be appropriately selected from the specific examples of the alkyl group described above, and the substitution can be single-point or multi-point substitution, and the present application is not particularly limited thereto.

[0038] The oxygen-containing heterocycle having 2 to 10 carbon atoms can be an unsaturated oxygen-containing heterocycle or a saturated oxygen-containing heterocycle, as long as the ring structure of the heterocycle has oxygen as a structural atom and the number of carbon atoms in the heterocycle is 2 to 10. For example, it can be unsubstituted or C1-C6 alkyl-substituted furan, unsubstituted or C1-C6 alkyl-substituted hydrogenated furan, unsubstituted or C1-C7 alkyl-substituted oxazole, unsubstituted or C1-C7 alkyl-substituted hydrogenated oxazole, unsubstituted or C1-C3 alkyl-substituted 1,3-benzodioxole, unsubstituted or C1-C2 alkyl-substituted 1,4-benzodioxole, and the like.

[0039] The sulfur-containing heterocycle having 2 to 10 carbon atoms can be an unsaturated sulfur-containing heterocycle or a saturated sulfur-containing heterocycle, as long as the ring structure of the heterocycle has sulfur as a structural atom and the number of carbon atoms in the heterocycle is 2 to 10. For example, it can be unsubstituted or C1-C6 alkyl-substituted thiophene, unsubstituted or C1-C6 alkyl-substituted hydrogenated thiophene, unsubstituted or C1-C7 alkyl-substituted thiazole, unsubstituted or C1-C7 alkyl-substituted hydrogenated thiazole, and the like.

[0040] wherein R 1 is selected from the group consisting of methyl, isopropyl, cyclopropyl, isobutyl, sec-butyl, and halogen; R 2 is selected from the group consisting of hydrogen, hydroxy, halogen, cyano, nitro, trifluoromethyl, trifluoromethoxy, C1-C6 hydrocarbyl, C1-C6 alkylamino, dioxomethylene, and dioxoethylene.

[0041] Preferably, R 1 selected from the group consisting of methyl; R 2 selected from the group consisting of methyl, benzyl, 4-trifluoromethylbenzyl, 2-bromo-4-methoxybenzyl, 3-bromobenzyl, phenyl, 3-methyl-4-bromophenyl, 3-nitrophenyl, 3,5-difluorophenyl, 3,5-dichlorophenyl.

[0042] In a preferred embodiment of the present application, the compound of general formula is selected from one of the compounds of the following formulae:

[0043]

[0044]

[0045]

[0046] The present application provides a method for preparing the acetophenone triazole derivative described above, which comprises: first, 1,3-resorcinol and halogenated benzene or halogenated nitrogen-containing heterocycle, halogenated oxygen-containing heterocycle, halogenated oxygen-containing heterocycle undergo substitution reaction under the catalysis of cuprous iodide / N,N-dimethyl glycine to generate intermediate 2b; compound 1 and intermediate 2b undergo acetylation under the action of acetic anhydride to generate intermediates 2a and 3c, respectively; 2a reacts with halogenated hydrocarbon under alkaline conditions to generate intermediate 3a; 2a and substituted carboxylic acid complete esterification under the action of DCC / DMAP to generate intermediate 3b.

[0047]

[0048] Intermediate 3 is further brominated under the action of copper bromide and then reacts with N-amino-1,2,4-triazole to generate the target product 4 (I and III); 4 (I and III) is further reacted under the action of nitrous acid to generate the target product 5 (II and IV).

[0049]

[0050] wherein, R 1 , R 2 As described above, the present application is not described here again.

[0051] In view of obtaining higher fungicidal and insecticidal active compounds, the acetophenone triazole derivative described in the present application is preferably selected from one or more of the following compounds:

[0052] 1H-1-(2'-(2"-hydroxy-4"-methoxy-5"methylphenyl)-2'-oxycarbonylethyl)-4-amino-1,2,4-triazole inner onium bromide (4a);

[0053] 1H-1-(2'-(2"-hydroxy-4"-(4"' -trifluoromethylbenzyl)oxy-5"-methylphenyl)-2'- oxycarbonylethyl)-4-amino-1,2,4-triazole inner bromide (4c);

[0054] 1-(2'-hydroxy-4'-(4"-trifluoromethylbenzyl)oxy-5'-methylphenyl)-2-(1H-1,2,4- triazolyl)ethanone (5c);

[0055] 1-(2'-hydroxy-4'-(4"-trifluoromethylbenzyl)oxy-5'-methylphenyl)-2-(1H-1,2,4- triazolyl)ethanone (5c);

[0056] 1-(2'-hydroxy-4'-(4"-trifluoromethylbenzyl)oxy-5'-methylphenyl)-2-(1H-1,2,4- triazolyl)ethanone (5c);

[0057] 1-(2'-hydroxy-4'-(4"-trifluoromethylbenzyl)oxy-5'-methylphenyl)-2-(1H-1,2,4- triazolyl)ethanone (5c);

[0058] The application provides the application of the compounds I / III (4) and II / V (5) in fungicidal aspects.

[0059] The compounds I / III (4) and II / V (5) provided by the application have high fungicidal activity, especially for one or more of F. solani, Cytospora sp., C. gloeosporioides, B. cinerea, F. graminearum and M. grisea.

[0060] In particular, the acetophenone triazole derivatives in the application have good fungicidal activity, wherein the compound 4c has inhibition rates of 90.44%, 62.40%, 96.23% and 80.10% on B. cinerea, F. graminearum, F. solani and M. grisea respectively at a concentration of 50.0 mg / L; and the compound 5c has inhibition rates of 90.56%, 73.09%, 93.64% and 74.00% on the four kinds of bacteria respectively at a concentration of 50.0 mg / L.

[0061] The application provides the application of the acetophenone A in insecticidal aspects.

[0062] The acetophenone A provided by the application has high insecticidal activity on one or more of aphids, armyworms, diamondback moths and cotton bollworms.

[0063] The application provides uses of the compounds I / III (4) and II / V (5) in insecticide.

[0064] The compounds I / III (4) and II / V (5) of the general formula provided by the application have good insecticidal activity, and in particular, the acetophenone A has high insecticidal activity on one or more of aphids, armyworms, diamondback moths and cotton bollworms.

[0065] In particular, the half effective lethal concentration (LC 50 ) of the acetophenone A on the peach aphid and the oriental armyworm is 79.29 mg / L and 570 mg / L respectively; the LC 50 of the compound 5a on the peach aphid and the oriental armyworm is 55.71 mg / L and 80 mg / L respectively; the LC 50 of the compounds 5e and 5d on the peach aphid is 13.78 mg / L and 14.37 mg / L respectively.

[0066] The compound of the general formula provided by the application can be directly used as an insecticide and fungicide, or can be used by adding an agriculturally acceptable carrier, or can be used in combination with other insecticides, acaricides and fungicides such as pyrimidifen, chlorfenapyr, etoxazole and fenpyroximate, and some of the combinations have a synergistic effect, and some have an additive effect.

[0067] The following examples and test results can be used to further illustrate the application, but do not mean to limit the application.

[0068] Example 1: Synthesis of acetophenone triazole derivatives 4a and 5a

[0069]

[0070] Synthesis of intermediate 2a-1 (acetophenone A)

[0071] To a 25 mL vial was added 2,4-dihydroxytoluene (2-2, 1.0 mmol) followed by 8 mL of boron trifluoride etherate, then slowly added acetic anhydride (1.2 mmol) and the system was stirred at 90 °C until the reaction was complete, about 8 h. The reaction system was poured into crushed ice and stirred for 10 min, extracted with ethyl acetate (2 x 10 mL), washed with H2O (2 x 10 mL) and saturated sodium chloride (2 x 10 mL), respectively, and the organic phase was combined and dried with anhydrous Na2SO4for 10 min. The solvent was removed by vacuum distillation, and the white solid natural product acetophenone A was obtained by silica gel column chromatography (PE:EA = 10:1). Yield 70%; NMR data: 1 H NMR (400 MHz, CDC13) δ 12.53 (s, 1H), 7.47 (s, 1H), 6.34 (s, 1H), 5.78 (s, 1H), 2.55 (s, 3H), 2.19 (s, 3H). 13 C NMR (100 MHz, CDC13) δ 202.61, 163.32, 161.02, 133.14, 115.92, 114.08, 103.07, 26.32, 15.11; Mass data: ESI-MS calcd for C9H9O3 [M-H] - 165.06. found: 165.11.

[0072] Synthesis of intermediate 3a-1

[0073] To a 5-methyl-2,4-dihydroxyacetophenone (166 mg, 1 mmol) solution in acetone (3 mL) was added potassium carbonate (276 mg, 2 mmol), methyl iodide (74.7 μL, 1.2 mmol), and refluxed for 8 h, and the solvent in the system was removed by vacuum distillation, and the crude product was purified by silica gel column chromatography (PE:EA = 15:1) to obtain compound 3a-1. White solid, yield 63%; melting point 94.0-95.0 °C; NMR data: 1 H NMR (400 MHz, CDC13) δ 12.68 (s, 1H), 7.39 (s, 1H), 6.33 (s, 1H), 3.82 (s, 3H), 2.51 (s, 3H), 2.11 (s, 3H). 13 C NMR (100 MHz, CDC13) δ 202.47, 164.38, 163.84, 131.74, 118.03, 112.96, 98.76, 55.64, 26.22, 15.58; Mass data: ESI-MS calcd for C 10 H 13 O3 [M+H] +181.09.found:181.30.

[0074] Synthesis of acetophenone triazole derivative 4a

[0075] To intermediate 3a-1 (10 mmol) and copper bromide (3.341 g, 15 mmol) was added ethyl acetate (15 mL) and refluxed at 65 °C for 8 h. The reaction generated copper bromide was filtered and the filtrate was washed with 5 mL of sodium bicarbonate three times. The organic phase was combined and dried over anhydrous Na2S04for 10 min. The solvent was removed from the reaction system under vacuum and the residue was purified by column chromatography (PE:DCM = 5:1-1:1) to obtain the bromination product. Then the bromination product (10 mmol) and 4-amino-1,2,4-triazole (1.008 g, 12 mmol) were added to isopropyl alcohol (30 mL) and heated at 80 °C for 8 h. After the system was cooled, it was evaporated to dryness under reduced pressure to obtain a residue, which was dissolved in dichloromethane (10 mL) and stirred at 0 °C for 30 min. The solid was precipitated, filtered and washed with dichloromethane (5 mL) to obtain the target compound 4a. White solid, yield 96%, melting point 222.7-223.2 °C; NMR data: 1 H NMR (400 MHz, DMSO-d6) δ 11.35 (s, 1H), 10.16 (s, 1H), 9.30 (s, 1H), 7.63 (d, J = 1.0 Hz, 1H), 7.16 (s, 2H), 6.58 (s, 1H), 5.99 (s, 2H), 3.85 (s, 3H), 2.08 (s, 3H). 13 C NMR (100 MHz, DMSO-d6) δ 189.50, 164.17, 161.13, 145.08, 144.18, 131.39, 118.08, 111.78, 98.88, 60.19, 55.94, 15.25. Mass spectrum data: ESI-MS calcd for C 12 H 15 N4O3 + [M] + 263.11.found:263.33.

[0076] Synthesis of acetophenone triazole derivative 5a

[0077] To a solution of compound 4a (1.56 mmol) in water (3.5 mL) was added concentrated hydrochloric acid (0.28 mL) at 0 °C, followed by dropwise addition of a solution of sodium nitrite (0.12 g, 1.72 mmol) dissolved in 0.5 mL of water. After the reaction mixture was stirred at room temperature for 1 h, the precipitate was filtered off and washed with 1 mL of water to give the target compound 5a. White solid, yield 89%, melting point 189.1-190.0 °C; NMR data: 1 H NMR (400 MHz, DMSO-d6) δ 11.54 (d, J = 1.0 Hz, 1H), 8.51 (s, 1H), 8.00 (s, 1H), 7.71 (d, J = 1.0 Hz, 1H), 6.55 (s, 1H), 5.83 (s, 2H), 3.86 (s, 3H), 2.10 (s, 2H). 13 C NMR (100 MHz, DMSO-d6) δ 194.32, 164.51, 162.21, 151.70, 146.21, 131.51, 118.26, 112.26, 99.41, 56.37, 56.20, 15.69. Mass spectral data: ESI-MS calcd for C 12 H 14 N3O3[M+H] + 248.11. found: 248.34.

[0078] Compounds 4b to 4e were completed by referring to the procedure of 4a; compounds 5b to 5e were completed by referring to the procedure of 5a.

[0079] The characterization results of the obtained compounds are shown as follows:

[0080] 1H-1-(2’-(2”-hydroxy-4”-benzyloxy-5”-methyl)phenyl-2’-oxycarbonylethyl)-4- amino-1,2,4-triazolium bromide (4b): white solid, yield 76%, melting point 207.8-209.5 °C; 1 H NMR (400 MHz, DMSO-d6) δ 11.54 (d, J = 1.0 Hz, 1H), 8.51 (s, 1H), 8.00 (s, 1H), 7.71 (d, J = 1.0 Hz, 1H), 6.55 (s, 1H), 5.83 (s, 2H), 3.86 (s, 3H), 2.10 (s, 2H). 13C NMR (100 MHz, DMSO-d6) δ 191.61, 189.58, 163.02, 160.92, 145.00, 144.07, 136.32, 131.10, 128.57, 128.02, 127.41, 118.35, 112.42, 100.59, 69.59, 60.49, 15.29. ESI-MS calcd for C 18 H 19 N4O3 + [M] + 339.15.found:339.41.

[0081] 1H-1-(2'-(2"-hydroxy-4"-(4"' -trifluoromethylbenzyl)oxy-5"-methyl)phenyl-2'- oxycarbonylethyl)-4-amino-1, 2, 4-triazolium bromide (4c): white solid, yield 94%, melting point 233.7-234.2 °C; 1 H NMR (400 MHz, DMSO-d6) δ 11.32 (s, 1H), 10.21 (s, 1H), 9.31 (s, 1H), 7.79 (d, J = 8.0 Hz, 2H), 7.70 (d, J = 9.0 Hz, 3H), 6.67 (s, 1H), 6.01 (s, 2H), 5.33 (s, 2H), 2.17 (s, 3H). 13 C NMR (100 MHz, DMSO-d6) δ 189.58, 162.65, 160.82, 145.48, 144.08, 141.23, 131.20, 128.45 (q, J = 31.6 Hz), 127.80, 125.45 (q, J = 3.8 Hz), 124.20 (q, J = 270.1 Hz), 117.77, 112.65, 99.78, 68.70, 60.14, 15.24. ESI-MS calcd for C 19 H 18 F3N4O3 + [M] + 407.13.found:407.48.

[0082] 1H-1-(2'-(2"-hydroxy-4"-(2"' -bromo-4"' -methoxybenzyl)oxy-5"-methylphenyl)-2'- oxycarbonylethyl)-4-amino-1, 2, 4-triazolium bromide (4d): white solid, yield 89%, melting point 202.1-203.9 °C; 1HNMR (400MHz, DMSO-d6) δ11.33(s,1H),10.16(s,1H),9.30(s,1H),7.67(s,1H),7.60(d,J=8.8Hz,1H),7.18(d,J=3. 2Hz,1H),7.16(s,2H),6.94(dd,J=8.8,3.1Hz,1H),6.68(s,1H),5.99(s,2H),5.15(s,2H),3.77(s,3H),2.15(s,3H). 13 C NMR(100MHz,DMSO-d6)δ189.82,163.04,161.20,159.27,145.49,144.57,136.61,133.95,1 31.67,118.77,116.26,115.89,113.30,113.07,100.45,70.16,60.81,56.59,15.71.ESI-MS calcd for C 19 H 20 BrN4O4 + [M] + 447.07.found:447.49.

[0083] 1H-1-(2'-(2”-hydroxy-4”-(3”'-bromobenzyl)oxy-5”-methylphenyl)-2'-oxycarbonylethyl)-4-amino-1,2,4-triazole lacton bromide (4e): white solid, yield 82%, melting point 221.0-222.8℃; 1 H NMR (400MHz, DMSO-d6) δ11.33(s,1H),10.19(s,1H),9.31(d,J=1.4Hz,1H),7.67(s,2H),7.55(dd,J=7.9,2.0Hz,1H), 7.50-7.47(m,1H),7.39(t,J=7.8Hz,1H),7.19(s,2H),6.65(d,J=1.5Hz,1H),6.01(s,2H),5.22(s,2H),2.15(s,3H). 13 C NMR(100MHz,DMSO-d6)δ189.56,162.71,160.82,145.02,144.09,139.17,131.18,130.8 6,130.82,129.99,126.35,122.18,118.30,112.61,100.15,68.21,60.17,14.91.ESI-MS calcd for C 18 H 18BrN4O3 + [M] + 417.06.found:417.46.

[0084] 1H-1-(2'-(2”-hydroxy-4”-benzyloxyphenyl)-2'-oxycarbonylethyl)-4-amino-1,2,4-triazole lacton bromide (4f): white solid, 78% yield, melting point 183.9-185.0℃; 1 H NMR (400MHz, DMSO-d6) δ11.43(s,1H),10.16(s,1H),9.30(s,1H),7.81(d,J=8.8Hz ,1H),7.48-7.34(m,5H),7.17(s,2H),6.70-6.65(m,2H),6.00(s,2H),5.19(s,2H). 13 C NMR(100MHz,DMSO-d6)δ189.40,164.88,162.03,145.00,144.10,136.18,13 2.06,128.55,128.14,127.84,113.79,108.20,102.03,69.66,60.40.ESI-MS calcd for C 17 H 17 N4O3 + [M] + 325.13.found:325.40.

[0085] 1-(2'-hydroxy-4'-benzyloxy-5'-methylphenyl)-2-(1H-1,2,4-triazolyl)acetone (5b): white solid, yield 89%, melting point 143-144.1℃; 1 H NMR (400MHz, CDCl3) δ11.86(s,1H),8.22(s,1H),8.01(s,1H),7.42(s,1H),7.41-7.33(m,5H),6.47(s,1H),5.59(s,2H),5.09(s,2H),2.21(s,3H). 13 C NMR (100MHz, CDCl3) δ193.29,164.52,164.35,152.06,135.77,129.66,128 .77,128.35,127.25,119.67,110.60,100.44,70.32,53.85,15.94.ESI-MS calcd forC 18 H 18 N3O3[M+H] +324.14. found: 324.45.

[0086] 1 -(2'-hydroxy-4'-(4"-trifluoromethylbenzyl)oxy-5'-methylphenyl)-2-(1 H- 1,2,4-triazolyl)ethanone (5c): white solid, yield 82%, melting point 223.0-225.0 °C; 1 H NMR (400 MHz, DMSO-d6) δ 11.31 (s, 1H), 10.19 (s, 1H), 9.30 (s, 1H), 7.80 (d, J = 8.1 Hz, 2H), 7.70 (d, J = 9.2 Hz, 3H), 7.19 (s, 2H), 6.66 (s, 1H), 6.01 (s, 2H), 5.34 (s, 2H), 3.35 (s, 2H), 2.19-2.15 (m, 3H). 13 C NMR (100 MHz, DMSO-d6) δ 189.60, 162.66, 160.85, 145.02, 144.09, 141.24, 131.22, 128.46 (q, J = 31.74 Hz), 127.82, 125.47 (q, J = 3.61 Hz), 124.22 (q, J = 270.3 Hz), 118.32, 112.67, 100.73, 68.70, 60.17, 16.45. ESI-MS calcd for C 19 H 17 F3N3O3[M+H] + 392.12. found: 391.51.

[0087] 1 -(2'-hydroxy-4'-(2"-bromo-4"-methoxybenzyl)oxy-5'-methylphenyl)-2-(1 H- 1,2,4-triazolyl)ethanone (5d): white solid, yield 53%, melting point 229.7-231.2 °C; 1 H NMR (400 MHz, DMSO-d6) δ 11.50 (s, 1H), 8.50 (d, J = 1.7 Hz, 1H), 8.00 (d, J = 1.7 Hz, 1H), 7.74 (s, 1H), 7.58 (d, J = 8.8 Hz, 1H), 7.18 (d, J = 3.1 Hz, 1H), 6.93 (dd, J = 8.8, 3.1 Hz, 1H), 6.65 (s, 1H), 5.82 (s, 2H), 5.15 (s, 2H), 3.77 (s, 3H), 2.15 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 193.72, 162.55, 161.39, 158.85, 151.25, 145.76, 136.25, 133.52, 131.34, 118.13, 115.99, 115.55, 112.80, 112.48, 100.10, 69.45, 56.05, 55.50, 15.32. ESI-MS calcd for C 19 H 19 BrN3O4[M+H] + 432.06. found: 432.48.

[0088] 1-(2'-hydroxy-4'-(3"-bromobenzyl)oxy-5'-methylphenyl)-2-(1H-1,2,4-triazolyl)ethanone (5e): white solid, yield 89%, melting point 150.0-151.6 °C. 1 H NMR (400 MHz, DMSO-d6) δ 11.35 (s, 1H), 10.22 (s, 1H), 9.33 (s, 1H), 7.69 (s, 2H), 7.57 (d, J = 7.9 Hz, 1H), 7.50 (d, J = 7.6 Hz, 1H), 7.43-7.39 (m, 1H), 6.67 (s, 1H), 6.02 (s, 2H), 5.24 (s, 2H), 2.16 (s, 3H). 13 C NMR (100 MHz, DMSO-d6) δ 189.58, 162.73, 160.86, 145.06, 144.12, 139.19, 131.20, 130.89, 130.85, 130.02, 126.96, 121.81, 118.32, 112.64, 100.21, 68.63, 60.23, 14.43. ESI-MS calcd for C 18 H 17 BrN3O3[M+H] + 402.05. found: 401.49.

[0089] 1-(2'-hydroxy-4'-benzyloxyphenyl)-2-(1H-1,2,4-triazolyl)ethanone (5f): white solid, yield 72%, melting point 133.4-135.3 °C. 1H NMR (400 MHz, DMSO-d6) δ 11.91 (s, 1H), 8.22 (s, 1H), 8.02 (s, 1H), 7.62 (s, 1H), 7.43 - 7.35 (m, 5H), 6.61 - 6.58 (m, 1H), 6.55 (d, J = 2.5 Hz, 1H), 5.60 (s, 2H), 5.11 (s, 2H). 13 C NMR (100 MHz, DMSO-d6) δ 193.60, 164.76, 162.60, 151.23, 146.35, 136.25, 132.08, 128.57, 128.15, 127.89, 113.79, 108.09, 102.02, 69.68, 56.25. ESI-MS calcd for C 17 H 16 N3O3 [M+H] + 310.12. found: 310.46.

[0090] Example 2: Synthesis of acetophenone triazole derivatives 4g and 5g

[0091]

[0092] The synthesis of intermediate 2a-2 was accomplished by following the procedure of 2a-1.

[0093] Synthesis of intermediate 3b-1

[0094] Acetic acid (0.75 mol) was dissolved in dichloromethane (2 mL) solution, compound 2a-2 (0.5 mmol) and 4-dimethylaminopyridine (6.01 mg, 0.05 mmol) were added. Then, the solution was cooled to 0 °C and after 15 min, N,N-dicyclohexylcarbodiimide (123.79 mg, 0.6 mmol) was added and the reaction was carried out at room temperature for 4 h. The mixture was vacuum distilled and finally purified by silica gel column chromatography (PE:EA = 20:1) to give compound 3b-1. Yellow solid, yield 75%, melting point 73.2-74.1 °C; 1 H NMR (400 MHz, CDCl3) δ 12.42 (s, 1H), 7.73 (d, J = 8.7 Hz, 1H), 6.72 (d, J = 2.3 Hz, 1H), 6.66 (dd, J = 8.7, 2.2 Hz, 1H), 2.59 (s, 3H), 2.29 (s, 3H). 13C NMR (100 MHz, CDC13) δ 203.58, 168.47, 163.89, 156.62, 131.96, 117.70, 112.90, 111.10, 26.64, 21.14. ESI-MS calcd for C 10 H 11 O4[M+H] + 195.07.found:195.08.

[0095] Compound 4g was completed by referring to the procedure of 4a; compound 5g was completed by referring to the procedure of 5a.

[0096] The results of the characterization of the resulting compound are shown below:

[0097] 1H-1-(2'-(2"-hydroxy-4"-acetoxyphenyl)-2'-oxocarbonylethyl)-4-amino-1,2,4-triazole inner bromide (4g): white solid, yield 63%, melting point 188.6-189.6 °C. 1 H NMR (400 MHz, DMSO-d6) δ 11.58 (s, 1H), 10.18 (s, 1H), 9.31 (s, 1H), 7.85 (d, J = 8.7 Hz, 1H), 7.20 (s, 1H), 6.90 (d, J = 2.1 Hz, 1H), 6.79 (dd, J = 8.7, 2.1 Hz, 1H), 6.03 (s, 2H), 2.29 (s, 3H). 13 C NMR (100 MHz, DMSO-d6) δ 190.12, 169.02, 160.92, 156.69, 145.44, 144.48, 131.98, 119.04, 114.20, 110.98, 61.72, 21.44. ESI-MS calcd for C 12 H 13 N4O4 + [M] + 277.09.found:277.32.

[0098] 1 -(2'-Hydroxy-4'-acetyloxy-phenyl)-2-(1 H-1,2,4-triazolyl)ethanone (5g): white solid, yield 65%, m.p. 169.8-171.2 °C;1H NMR (400 MHz, DMSO-d6) δ 11.48 (s, 1 H), 8.51 (s, 1 H), 8.01 (s, 1 H), 7.86 (d, J = 8.7 Hz, 1 H), 6.83 (d, J = 2.2 Hz, 1 H), 6.77 (dd, J = 8.7, 2.2 Hz, 1 H), 5.83 (s, 2H), 2.29 (s, 3H).13C NMR (100 MHz, DMSO-d6) δ 193.70, 169.05, 160.92, 156.38, 151.65, 146.12, 132.01, 119.12, 114.01, 1 10.99, 58.07, 21.42. ESI-MS calcd for C 12 H 12 N3O4[M+H] + 262.08. found: 262.33.

[0099] Compounds 4h to 4i were completed by referring to the procedure of 4g; compounds 5h to 5i were completed by referring to the procedure of 5g.

[0100] The results of the characterization of the resulting compounds are shown below:

[0101] 1 H-1 -(2'-(2"-hydroxy-4"-propionyloxyphenyl)-2'-oxocarbonylethyl)-4-amino-1,2,4- triazolium bromide (4h): white solid, yield 74%, m.p. 195.6-196.6 °C. 1 H NMR (400 MHz, DMSO-d6) δ 1 1.59 (s, 1 H), 10.1 1 (d, J = 1.6 Hz, 1 H), 9.30 (s, 1 H), 7.85 (d, J = 8.8 Hz, 1 H), 7.14 (s, 2H), 6.87 (d, J = 2.2 Hz, 1 H), 6.79 (dd, J = 8.7, 2.2 Hz, 1 H), 6.01 (s, 2H), 2.63 (q, J = 7.5 Hz, 2H), 1.13 (t, J = 7.5 Hz, 3H). 13 C NMR (100 MHz, DMSO-d6) δ 189.65, 171.95, 160.47, 156.34, 145.00, 144.06, 131.52, 119.22, 1 13.74, 1 10.95, 61.25, 26.96, 8.71. ESI-MS calcd for C 13 H 15 N4O4+ [M] + 291.11. found: 291.32.

[0102] 1H-1-(2'-(2"-hydroxy-4"-acetyloxy-5"-methylphenyl)-2'-oxocarbonyl ethyl)-4-amino-1,2,4-triazole inner bromide (4i): white solid, yield 81.5%, melting point 225.0-226.5 °C; 1 H NMR (400 MHz, DMSO-d6) δ 11.34 (s, 1H), 10.19 (s, 1H), 9.31 (s, 1H), 7.71 (s, 1H), 7.20 (s, 2H), 6.85 (s, 1H), 6.02 (s, 2H), 2.33 (s, 3H), 2.06 (s, 3H). 13 C NMR (100 MHz, DMSO-d6) δ 190.21, 168.83, 158.89, 155.29, 145.45, 144.47, 132.38, 121.98, 119.06, 111.53, 61.68, 21.11, 15.33. ESI-MS calcd for C 13 H 15 N4O4 + [M] + 291.11. found: 291.32.

[0103] (2'-hydroxy-4'-propionyloxy-phenyl)-2-(1H-1,2,4-triazolyl)ethanone (5h): white solid, yield 73%, melting point 153.5-154.9 °C. 1 H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 8.46 (s, 1H), 7.96 (s, 1H), 7.81 (d, J = 8.6 Hz, 1H), 6.77 (d, J = 2.3 Hz, 1H), 6.72 (dd, J = 8.7, 2.2 Hz, 1H), 5.78 (s, 2H), 2.57 (q, J = 7.5 Hz, 2H), 1.07 (t, J = 7.5 Hz, 3H). 13 C NMR (100 MHz, DMSO-d6) δ 193.70, 172.44, 160.96, 156.48, 151.62, 146.11, 132.01, 119.05, 114.01, 110.96, 93.29, 58.07, 27.41, 9.18. ESI-MS calcd for C 13 H 14 N3O4[M+H] +276.10. found: 276.35.

[0104] 1-(2'-hydroxy-4'-acetoxy-5'-methylphenyl)-2-(1H-1,2,4-triazolyl)ethanone (5i): white solid, yield 95%, melting point 204.9-206.4 °C. 1 H NMR (400 MHz, DMSO-d6) δ 11.23 (s, 1H), 8.52 (s, 1H), 8.01 (s, 1H), 7.74 (s, 1H), 6.79 (s, 1H), 5.82 (s, 2H), 2.32 (s, 3H), 2.07 (s, 3H). 13 C NMR (100 MHz, DMSO-d6) δ 193.79, 168.84, 158.89, 154.97, 151.62, 132.51, 121.76, 119.17, 111.49, 58.02, 21.09, 15.34. ESI-MS calcd for C 13 H 14 N3O4[M+H] + 276.10. found: 276.34.

[0105] Example 3: Synthesis of acetophenone triazole derivatives 4j and 5j

[0106]

[0107] Synthesis of intermediate 2b-1

[0108] Resorcinol (10 mmol), iodobenzene (12 mmol), cuprous iodide (0.1 mmol), N,N- dimethylglycine (0.1 mmol), potassium phosphate (20 mmol) were added to 50 mL of anhydrous dimethyl sulfoxide under the protection of nitrogen, and reacted at 90 °C for 24 h. After adding pure water, it was extracted with ethyl acetate (3 x 30 mL), washed with H2O (2 x 30 mL) and saturated NaCl (2 x 30 mL), and the organic phase was combined and dried with anhydrous sodium sulfate for 10 min. The solvent was removed by distillation under reduced pressure, and the compound 2b-1 was purified by column chromatography (PE:EA = 80:1).

[0109] Synthesis of intermediate 3c-1 was completed by referring to the steps of 2a-1.

[0110] Compound 4j was completed by referring to the steps of 4a; compound 5j was completed by referring to the steps of 5a.

[0111] The characterization results of the obtained compounds are as follows:

[0112] 1H-1-(2'-(2"-hydroxy-4"-phenoxyphenyl)-2'-oxycarbonylethyl)-4-amino-1,2,4-triazolium bromide (4j): white solid, yield 74%, melting point 201.6-203.0 °C; 1 H NMR (400 MHz, DMSO-d6) δ 11.40 (s, 1H), 10.19 (s, 1H), 9.30 (s, 1H), 7.84 (d, J = 8.9 Hz, 1H), 7.52-7.47 (m, 2H), 7.32-7.27 (m, 1H), 7.19-7.15 (m, 2H), 6.61 (dd, J = 8.9, 2.4 Hz, 1H), 6.53 (d, J = 2.4 Hz, 1H), 5.98 (s, 2H). 13 CNMR (100 MHz, DMSO-d6) δ 188.95, 164.00, 161.48, 154.20, 144.95, 144.02, 132.47, 130.45, 125.34, 120.63, 115.68, 109.35, 104.13, 61.01. ESI-MS calcd for C 16 H 15 N4O3 + [M] + 311.11. found: 311.36.

[0113] 1-(2'-(2"-hydroxy-4"-phenoxyphenyl)-2'-oxycarbonylethyl)-4-amino-1,2,4-triazolium bromide (4j): white solid, yield 74%, melting point 201.6-203.0 °C; 1 H NMR (400 MHz, DMSO-d6) δ 11.40 (s, 1H), 10.19 (s, 1H), 9.30 (s, 1H), 7.84 (d, J = 8.9 Hz, 1H), 7.52-7.47 (m, 2H), 7.32-7.27 (m, 1H), 7.19-7.15 (m, 2H), 6.61 (dd, J = 8.9, 2.4 Hz, 1H), 6.53 (d, J = 2.4 Hz, 1H), 5.98 (s, 2H). 13 CNMR (100 MHz, DMSO-d6) δ 192.55, 163.69, 161.66, 154.30, 150.75, 145.56, 132.48, 130.42, 125.26, 120.59, 115.72, 109.14, 104.30, 57.37. ESI-MS calcd for C 16 H 14 N3O3[M+H] +296.11.found:296.42.

[0114] Compounds 4k to 4n were prepared by following the procedure described for 4j; compounds 5k to 5n were prepared by following the procedure described for 5j.

[0115] The results of the characterization of the obtained compounds are shown below:

[0116] 1H-1-(2'-(2"-hydroxy-4"-(3"' -methyl-4"' -bromophenoxy)phenyl)-2'-oxocarbonylethyl)-4- amino-1, 2, 4-triazolium bromide (4k): white solid, yield 76%, melting point 194.9-196.3 °C; 1 H NMR (400 MHz, DMSO-d6) δ 11.41 (s, 1H), 10.15 (d, J = 45.3 Hz, 1H), 9.29 (d, J = 4.5 Hz, 1H), 7.83 (d, J = 9.0 Hz, 1H), 7.68 (dd, J = 8.8, 3.0 Hz, 1H), 7.26-7.11 (m, 3H), 6.97 (dd, J = 8.5, 3.0 Hz, 1H), 6.63 (dt, J = 11.4, 2.4 Hz, 1H), 6.50 (d, J = 2.4 Hz, 1H), 5.96 (d, J = 9.9 Hz, 2H), 2.36 (s, 3).13C NMR (100 MHz, DMSO-d6) δ 188.93, 163.62, 161.42, 153.64, 145.00, 144.08, 139.77, 133.72, 132.54, 123.19, 120.11, 119.87, 115.96, 109.46, 104.34, 61.07, 22.49. ESI-MS calcd for C 17 H 16 BrN4O3 + [M] + 403.04.found:403.40.

[0117] 1H-1-(2'-(2"-hydroxy-4"-(3"' -methyl-4"' -bromophenoxy)phenyl)-2'-oxocarbonylethyl)-4- amino-1, 2, 4-triazolium bromide (4k): white solid, yield 76%, melting point 194.9-196.3 °C; 1H NMR (400 MHz, DMSO-d6) δ 11.54 (s, 1H), 10.26 - 10.08 (m, 1H), 9.30 (d, J = 3.2 Hz, 1H), 8.16 - 8.10 (m, 1H), 7.93 (t, J = 2.3 Hz, 1H), 7.88 (d, J = 8.8 Hz, 1H), 7.78 (t, J = 8.2 Hz, 1H), 7.67 (ddd, J = 8.1, 2.4, 1.0 Hz, 1H), 7.14 (s, 2H), 6.77 - 6.60 (m, 2H), 6.00 (d, J = 7.2 Hz, 2H). 13 C NMR (100 MHz, DMSO-d6) δ 189.64, 161.90, 155.72, 149.42, 145.47, 144.55, 133.19, 132.27, 127.38, 120.26, 117.29, 115.25, 110.41, 106.06, 61.59. ESI-MS calcd for C 16 H 14 N5O5 + [M] + 356.10. found: 356.41.

[0118] 1H-1-(2'-(2"-hydroxy-4"-(3"',4"' -difluorophenoxy)phenyl)-2'-oxocarbonylethyl)-4- amino-1,2,4-triazolium bromide (4m): white solid, yield 82%, melting point 187.3-189.2 °C; 1 H NMR (400 MHz, DMSO-d6) δ 11.54 (s, 1H), 10.26 - 10.08 (m, 1H), 9.30 (d, J = 3.2 Hz, 1H), 8.16 - 8.10 (m, 1H), 7.93 (t, J = 2.3 Hz, 1H), 7.88 (d, J = 8.8 Hz, 1H), 7.78 (t, J = 8.2 Hz, 1H), 7.67 (ddd, J = 8.1, 2.4, 1.0 Hz, 1H), 7.14 (s, 2H), 6.77 - 6.60 (m, 2H), 6.00 (d, J = 7.2 Hz, 2H). 13C NMR (100 MHz, DMSO-d6) δ 189.07, 163.41, 161.47, 150.44 (dd, J = 8.8, 2.7 Hz), 149.81 (dd, J = 248.0, 14.0 Hz), 146.99 (dd, J = 243.1, 12.5 Hz), 144.97, 144.03, 132.57, 118.57 (d, J = 18.6 Hz), 117.44 (dd, J = 6.6, 3.5 Hz), 116.15, 110.84 (d, J = 19.5 Hz), 109.23, 104.47, 61.04. ESI-MS calcd for C 16 H 13 F2N4O3 + [M] + 347.10.found:347.40.

[0119] 1H-1-(2'-(2"-hydroxy-4"-(3"'-methyl-4"'-chlorophenoxy)phenyl)-2'-oxocarbonyl- ethyl)-4-amino-1,2,4-triazolium bromide (4j): white solid, yield 91%, melting point 205.1-207.0 °C; 1 H NMR (400 MHz, DMSO-d6) δ 11.52 (s, 1H), 10.20 (s, 1H), 9.31 (s, 1H), 7.86 (d, J = 8.8 Hz, 1H), 7.53 (s, 1H), 7.30 (t, J = 1.3 Hz, 2H), 7.21 (s, 2H), 6.70-6.64 (m, 2H), 6.00 (s, 2H). 13 C NMR (100 MHz, DMSO-d6) δ 189.10, 162.28, 161.37, 156.10, 145.00, 144.05, 135.17, 132.68, 124.42, 119.88, 116.84, 109.94, 105.47, 61.17. ESI-MS calcd for C 16 H 13 C l2 N4O3 + [M] + 379.04.found:379.40.

[0120] 2-(2'-hydroxy-4'-(3"-methyl-4"-bromophenoxy)phenyl)-2-(1H-1,2,4-triazolyl)ethanone (5k): white solid, yield 84%, melting point 150.2-151.3 °C; 1H NMR (400 MHz, CDC13) δ 11.77 (s, 1H), 8.22 (s, 1H), 8.01 (s, 1H), 7.67 (d, J = 9.0 Hz, 1H), 7.54 (d, J = 8.5 Hz, 1H), 6.98 (d, J = 2.9 Hz, 1H), 6.80 (dd, J = 8.6, 2.9 Hz, 1H), 6.57 (dd, J = 8.9, 2.4 Hz, 1H), 6.41 (d, J = 2.5 Hz, 1H), 5.62 (s, 2H), 2.39 (s, 3H). 13 C NMR (100 MHz, CDC13) δ 193.89, 165.61, 165.37, 153.30, 140.35, 133.85, 130.88, 123.25, 121.05, 119.93, 112.71, 109.80, 105.31, 54.05, 23.21. ESI-MS calcd for C 17 H 15 Br N3O3 [M+H] + 388.03. found: 388.45.

[0121] 2-(2'-Hydroxy-4'-(3"-nitrophenoxy)phenyl)-2-(1H-1,2,4-triazolyl)ethanone (51): white solid, yield 93%, melting point 162.7-164.1 °C; 1 H NMR (400 MHz, DMSO-d6) δ 11.48 (s, 1H), 8.52 (s, 1H), 8.11 (dd, J = 8.3, 2.2 Hz, 1H), 8.01 (s, 1H), 7.92 (dd, J = 4.7, 2.5 Hz, 2H), 7.76 (t, J = 8.2 Hz, 1H), 7.65 (dd, J = 8.2, 2.5 Hz, 1H), 6.69 (dd, J = 8.8, 2.4 Hz, 1H), 6.62 (d, J = 2.4 Hz, 1H), 5.82 (s, 2H). 13 C NMR (100 MHz, DMSO-d6) δ 193.36, 162.54, 162.03, 155.82, 149.42, 133.18, 132.18, 127.26, 120.14, 117.31, 115.20, 110.21, 106.18, 57.82. ESI-MS calcd for C 16 H 13 N4O5 [M+H] + 341.09. found: 341.47.

[0122] 2-(2'-hydroxy-4'-(3",4"-difluorophenoxy)phenyl)-2-(1 H-1,2,4-triazolyl)ethanone (5m): white solid, yield 92%, melting point 188.6-190.3 °C; 1 H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 8.50 (s, 1H), 7.99 (s, 1H), 7.87 (d, J = 8.8 Hz, 1H), 7.60-7.50 (m, 1H), 7.42 (ddd, J = 11.5, 6.8, 2.9 Hz, 1H), 7.06 (ddd, J = 8.7, 4.2, 2.5 Hz, 1H), 6.61 (dd, J = 8.9, 2.4 Hz, 1H), 6.51 (d, J = 2.4 Hz, 1H), 5.79 (s, 2H). 13 C NMR (100 MHz, DMSO-d6) δ 192.84, 163.13, 161.62, 150.54 (dd, J = 8.7, 2.9 Hz), 149.81 (dd, J = 248.0, 14.0 Hz), 146.99 (dd, J = 243.2, 12.5 Hz), 132.59, 118.51 (d, J = 18.6 Hz), 117.36 (dd, J = 6.5, 3.4 Hz), 116.17, 110.80 (d, J = 19.6 Hz), 109.06, 104.56, 57.23. ESI-MS calcd for C 16 H 12 F2N3O3[M+H] + 332.09. found: 331.45.

[0123] 2-(2'-hydroxy-4'-(3",4"-difluorophenoxy)phenyl)-2-(1 H-1,2,4-triazolyl)ethanone (5m): white solid, yield 92%, melting point 188.6-190.3 °C; 1 H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 8.50 (s, 1H), 7.99 (s, 1H), 7.87 (d, J = 8.8 Hz, 1H), 7.60-7.50 (m, 1H), 7.42 (ddd, J = 11.5, 6.8, 2.9 Hz, 1H), 7.06 (ddd, J = 8.7, 4.2, 2.5 Hz, 1H), 6.61 (dd, J = 8.9, 2.4 Hz, 1H), 6.51 (d, J = 2.4 Hz, 1H), 5.79 (s, 2H). 13C NMR (101 MHz, DMSO-d6) δ 189.53, 162.79, 161.81, 156.53, 145.48, 144.55, 135.63, 133.14, 125.78, 119.89, 117.28, 110.41, 105.86, 61.25. ESI-MS calcd for C 16 H 12 C l2 N3O3[M+H] + 364.03.found:363.45.

[0124] The compounds in the present application can be prepared by the above-mentioned or similar methods, and the corresponding raw materials can be selected according to the difference of substituents and the difference of substituent positions.

[0125] Example 4: Anti-bacterial activity determination

[0126] The inhibition activity of the compounds on different plant-derived fungi was determined by mycelial growth rate method. Specifically, the compound to be screened was configured into a 10 mg / mL mother liquor, 75 μL (50 ppm, same below) was added into 20 mL solid culture medium and mixed uniformly. The test strain was pre-activated, and a sufficient number of fungus cakes were prepared by using a puncher with an inner diameter of 5 mm. The fungus cakes were placed on the solidified culture medium with a sterile inoculation needle, the mycelium was faced downward, and the fungus cakes were pressed gently to make them tightly contact with the culture medium. Three fungus cakes of the same strain were placed in each Petri dish. The Petri dishes after inoculation were placed in a constant temperature incubator at 26-28°C for dark culture, and the radial length of the fungal colonies was measured after 48-96 h (cross method, taking the average value).

[0127] The corresponding DMSO solvent system was used as a blank control, and carbendazim was used as a positive control. Inhibition rate (%) = (C-T) / (C-5mm) x 100%, C is the colony diameter (mm) of the blank control group, and T is the colony diameter (mm) of the treatment group or the positive control group.

[0128] Table 1, acetophenone triazole derivative 4 (I) series fungicidal activity

[0129]

[0130] B.c.: B. cinerea; C.g.: C. gloeosporioides; C.sp.: Cytospora sp; F.g.: F. graminearum; F.s.: F. solani; M.g.: M. grisea; HMX: Hymexazol.

[0131] Table 2, fungicidal activity of acetophenone triazole derivatives 5 (II) series

[0132]

[0133] B.c.: B. cinerea; C.g.: C. gloeosporioides; C.sp.: Cytospora sp; F.g.: F. graminearum; F.s.: F. solani; M.g.: M. grisea; HMX: Hymexazol.

[0134] The results in Table 1 and Table 2 show that the compounds I / III (4) and II / V (5) of the above general formula have high fungicidal activity, especially against one or more of the following: F. solani, Cytospora sp., C. gloeosporioides, B. cinerea, F. graminearum and M. grisea.

[0135] In particular, the acetophenone triazole derivatives of the present application exhibit good fungicidal activity, wherein compound 4c exhibits 90.44%, 62.40%, 96.23%, and 80.10% inhibition rates against B. cinerea, F. graminearum, F. solani and M. grisea, respectively, at a concentration of 50.0 mg / L; and compound 5c exhibits 90.56%, 73.09%, 93.64%, and 74.00% inhibition rates against the four fungi, respectively, at a concentration of 50.0 mg / L.

[0136] Example 5: Determination of insecticidal activity

[0137] The method for determining insecticidal activity is as follows:

[0138] Activity test of armyworm

[0139] Activity test method of armyworm: The leaf dipping method proposed by the International Resistance Action Committee (IRAC) was used. 2 mg of the sample was weighed on an analytical balance in a 10 mL beaker, dissolved in 50 uL of acetone (analytical pure), and made into a 500 ppm solution with water. The leaf with a diameter of about 5-6 cm was dipped into the solution for 5-6 seconds, taken out, dried on absorbent paper, placed in a designated petri dish, 10 3rd instar larvae were introduced, and placed in a 27 ± 1 °C insect rearing room. The results were checked after 2 days of observation.

[0140] Activity test of aphids

[0141] Activity test method for aphids: leaf dipping method. After preparing the required concentration of the solution, cabbage leaves were dipped into the solution for 5-6 seconds, removed, and placed on absorbent paper to dry. The leaves were then placed in a designated petri dish and 20 aphids were introduced into the dish. The dish was then placed in a rearing chamber and the results were observed after 1 day.

[0142] Activity test method for aphids: leaf dipping method. After preparing the required concentration of the solution, cabbage leaves were dipped into the solution for 5-6 seconds, removed, and placed on absorbent paper to dry. The leaves were then placed in a designated petri dish and 20 aphids were introduced into the dish. The dish was then placed in a rearing chamber and the results were observed after 1 day.

[0143] Activity test method for aphids: leaf dipping method. After preparing the required concentration of the solution, cabbage leaves were dipped into the solution for 5-6 seconds, removed, and placed on absorbent paper to dry. The leaves were then placed in a designated petri dish and 20 aphids were introduced into the dish. The dish was then placed in a rearing chamber and the results were observed after 1 day.

[0144] Activity test method for aphids: leaf dipping method. After preparing the required concentration of the solution, cabbage leaves were dipped into the solution for 5-6 seconds, removed, and placed on absorbent paper to dry. The leaves were then placed in a designated petri dish and 20 aphids were introduced into the dish. The dish was then placed in a rearing chamber and the results were observed after 1 day.

[0145] Activity test method for aphids: leaf dipping method. After preparing the required concentration of the solution, cabbage leaves were dipped into the solution for 5-6 seconds, removed, and placed on absorbent paper to dry. The leaves were then placed in a designated petri dish and 20 aphids were introduced into the dish. The dish was then placed in a rearing chamber and the results were observed after 1 day.

[0146] Table 3. Fungicidal activity of acetophenone triazole derivatives

[0147]

[0148] Note: a 48-hour activity data; b 24-hour activity data; c 2a-1: acetophenone A; - indicates not tested.

[0149] The results in Table 3 show that the compounds of general formula I / III (4) and II / V (5) have good insecticidal activity, particularly high insecticidal activity against one or more of aphids and armyworms.

[0150] In particular, the LC50 of acetophenone A against Myzus persicae and Mythimna separata was 79.29 mg / L and 570 mg / L, respectively; the LC50 of compound 5a against Myzus persicae and Mythimna separata was 55.71 mg / L and 80 mg / L, respectively; and the LC50 of compounds 5e and 5d against Myzus persicae was 13.78 mg / L and 14.37 mg / L, respectively. 50 50 50

[0151] ​​​Table 4, insecticidal activity of acetophenone

[0152]

[0153] Note: a, 48-hour activity data; b 24-hour activity data;

[0154] The results in Table 4 show that acetophenone A has high insecticidal activity against one or more of aphids, armyworms, diamondback moths, and bollworms.

[0155] The compounds I / III (4) and II / V (5) of the general formula of the present application have good insecticidal activity, particularly against one or more of aphids, armyworms, diamondback moths, and bollworms.

[0156] In particular, the half effective lethal concentration (LC 50 ) of acetophenone A against Myzus persicae and Pseudaletia separata is 79.29 mg / L and 570 mg / L, respectively; the LC 50 of compound 5a against Myzus persicae and Pseudaletia separata is 55.71 mg / L and 80 mg / L, respectively; the LC 50 of compound 5e and 5d against Myzus persicae is 13.78 mg / L and 14.37 mg / L, respectively.

[0157] The preferred embodiments of the present application are described in detail above, but the present disclosure is not limited to the specific details of the above embodiments, and various simple modifications can be made to the technical solutions of the present disclosure within the technical concept of the present disclosure, and these simple modifications all belong to the protection scope of the present disclosure.

[0158] In addition, it should be noted that each specific technical feature described in the above specific embodiments can be combined in any appropriate manner without contradiction, and in order to avoid unnecessary repetition, the present disclosure will not further describe various possible combination manners.

[0159] Furthermore, various different embodiments of the present disclosure can also be combined in any manner, as long as they do not deviate from the idea of the present disclosure, and they should also be considered as disclosed by the present disclosure.

Claims

1. A triazole derivative of 2,4-dihydroxy-5-methylacetophenone, characterized in that, The derivative is one of the compounds shown in the following formula; ， ； 2. The application of the triazole derivative of 2,4-dihydroxy-5-methyl-acetophenone according to claim 1 in the preparation of an insecticide, wherein the insecticide is used to control aphids and / or armyworms. 3.2, Application of 4-dihydroxy-5-methylacetophenone in the preparation of insecticides for the control of at least one of aphids, armyworms, diamondback moths and bollworms.

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