2-phenoxy-2-(1h-1,2,4-triazol)-acetophenone compounds, and preparation method and application thereof

Abstract

The application discloses a 2-phenoxy-2-(1H-1,2,4-triazole)-acetophenone compound and a preparation method and application thereof. A structural formula of the compound is shown as formula I. The application provides a 2-phenoxy-2-(1H-1,2,4-triazol)-acetophenone compound which is simple in structure, convenient in synthesis and high in biological activity. The compound is subjected to Arabidopsis thaliana primary rosette leaf branching, Arabidopsis thaliana main root elongation, Arabidopsis thaliana hypocotyl elongation and rice tillering tests. The results show that the compound has good promoting activity on Arabidopsis thaliana primary rosette branching, rice tillering and Arabidopsis thaliana main root elongation, and is a plant growth regulator with wide application prospect.

Description

Technical Field

[0001] This invention belongs to the field of plant growth regulator technology, specifically relating to a 2-phenoxy-2-(1H-1,2,4-triazole)-acetophenone compound with strigolactone biosynthesis inhibitor activity, its preparation method and application. Background Technology

[0002] Plant growth regulators, as safe and environmentally friendly chemical pesticides, are widely used in agricultural production, playing a significant role in crop growth regulation and weed control. Strigolactones (SLs) are a novel class of natural plant hormones that have attracted considerable attention in recent years. As a class of small carotenoid terpene lactones, strigolactones were first discovered in the root exudates of cotton in 1966. In recent years, with advancements in science and technology, more and more strigolactones have been discovered; currently, more than 30 strigolactones have been found in different plant varieties.

[0003] Dwarfing and multibranching are ideal traits for improving crop yield and lodging resistance in agricultural production. Strigolactones, as a class of naturally occurring plant signaling molecules, can effectively regulate the development of the aboveground parts and roots of plants, such as the formation of primary roots and lateral roots, the growth of lateral buds and branching / tillering, as well as stimulating the germination of seeds of root-parasitic weeds.

[0004] Strigolactone biosynthesis inhibitors are a class of small chemical molecules that can inhibit the biosynthesis of endogenous strigolactones in plants, thereby regulating the corresponding physiological processes. In recent years, strigolactones have received widespread attention, and research on strigolactone inhibitors has become increasingly common in order to better explore more new physiological functions and mechanisms of action of strigolactones. Therefore, designing and synthesizing simple and novel strigolactone biosynthesis inhibitors is of great significance. Summary of the Invention

[0005] The purpose of this invention is to provide a 2-phenoxy-2-(1H-1,2,4-triazole)-acetophenone compound with strigolactone biosynthesis inhibitor activity, its preparation method, and its application. This 2-phenoxy-2-(1H-1,2,4-triazole)-acetophenone compound plays an important regulatory role in plant growth and can be used as a plant growth regulator in agriculture.

[0006] One object of this invention is to provide 2-phenoxy-2-(1H-1,2,4-triazole)-acetophenone compounds, the structural formula of which is shown in Formula I:

[0007]

[0008] In Equation I, R1 Selected from at least one of the following: fluorine, chlorine, bromine, C1-C6 alkyl (such as methyl), C1-C6 alkoxy (such as methoxy), halogen-substituted C1-C6 alkyl (such as trifluoromethyl);

[0009] R 2 for Where n = 1-6, specifically 4; or R 2 for

[0010] R 2 for R 1 Preferably, it contains methyl, methoxy, trifluoromethyl, and at least one of fluorine, chlorine, and bromine;

[0011] R 2 for R 1 Preferably, it contains at least one of methyl, methoxy, trifluoromethyl, fluorine, chlorine, and bromine.

[0012] Specifically, the compound represented by Formula I is any one of the following compounds:

[0013]

[0014]

[0015] The 2-phenoxy-2-(1H-1,2,4-triazole)-acetophenone compounds shown in Formula I above are prepared by a method comprising the following steps:

[0016] 1) Under the action of an acid-binding agent, the compound shown in Formula II is reacted with 1H-1,2,4-triazole to obtain the 2-(1H-1,2,4-triazole)-acetophenone compound shown in Formula III;

[0017]

[0018] In equations II and III, R 1 The definition of R is the same as in formula I. 1 Definition;

[0019] 2) The compound shown in Formula IV is reacted with phenol to obtain the compound shown in Formula V;

[0020]

[0021] Among them, R in equations IV and V 2 The definition of R is the same as in Equation I. 2 Definition;

[0022] 3) Under the action of an acid-binding agent, the compound shown in Formula III is reacted with the compound shown in Formula V to obtain the 2-phenoxy-2-(1H-1,2,4-triazole)-acetophenone compound shown in Formula I.

[0023] In step 1) of the above method, the molar ratio of the compound shown in Formula II to 1H-1,2,4-triazole can be 1:1 to 2, specifically 1:1.5;

[0024] The acid-binding agent is at least one of triethylamine and potassium carbonate;

[0025] The reaction is carried out in a solvent:

[0026] The solvent is selected from at least one of acetone and dichloromethane;

[0027] The reaction was carried out at room temperature for 4-8 hours.

[0028] In step 2), the molar ratio of the compound shown in formula IV to phenol is 1 to 2:1, specifically 1.5:1.

[0029] The reaction is carried out in a solvent; the solvent is at least one of ultra-dry dichloromethane and N,N-dimethylformamide.

[0030] The reaction was carried out at room temperature for 6-12 hours.

[0031] In step 3), the molar ratio of the compound shown in formula III to the compound shown in formula V is 1:1 to 2, specifically 1:2;

[0032] The reaction is carried out in a solvent; the solvent is at least one of dichloromethane and dimethyl sulfoxide.

[0033] The acid-binding agent is at least one of sodium hydroxide and potassium hydroxide;

[0034] The reaction was carried out at room temperature for 6-8 hours.

[0035] The above method may further include purifying the system obtained in step 3), wherein the purification method is column chromatography separation, and the solvent used is ethyl acetate and petroleum ether in a volume ratio of 1:5.

[0036] The application of 2-phenoxy-2-(1H-1,2,4-triazole)-acetophenone compounds, as shown in Formula I, as plant growth regulators.

[0037] The regulatory effects of the plant regulators include any one of the following:

[0038] 1) Promotes branching development in plants;

[0039] 2) Inhibits the germination of seeds of root-parasitic weeds;

[0040] 3) Promotes the elongation of the hypocotyl in plant seedlings;

[0041] 4) Promotes the elongation of the plant's taproot;

[0042] 5) Inhibits the growth of root hairs in plants;

[0043] 6) Delays the senescence of plant leaves.

[0044] The plants mentioned can be dicotyledons and monocotyledons, specifically Arabidopsis thaliana, rice, corn, wheat, or cotton.

[0045] The root parasitic weeds mentioned can specifically be broomrape and strigophyte.

[0046] The present invention also provides a plant growth regulator containing a 2-phenoxy-2-(1H-1,2,4-triazole)-acetophenone compound as shown in Formula I above.

[0047] This invention provides a 2-phenoxy-2-(1H-1,2,4-triazole)-acetophenone compound with a simple structure, convenient synthesis, and high biological activity. Tests were conducted on this compound on Arabidopsis thaliana primary rosette branching, Arabidopsis thaliana taproot elongation, Arabidopsis thaliana hypocotyl elongation, and rice tillering. The results show that this compound has good promoting activity on Arabidopsis thaliana primary rosette branching, rice tillering, and Arabidopsis thaliana taproot elongation, making it a plant growth regulator with broad application prospects. Detailed Implementation

[0048] The present invention will now be described in further detail with reference to specific embodiments. The given embodiments are merely illustrative of the invention and not intended to limit its scope. The embodiments provided below can serve as a guide for further improvements by those skilled in the art and do not constitute a limitation on the invention in any way.

[0049] Unless otherwise specified, the experimental methods used in the following examples are conventional methods, performed according to the techniques or conditions described in the literature in this field or according to the product instructions. Unless otherwise specified, the materials and reagents used in the following examples are commercially available.

[0050] In the following examples, the synthesis of compounds A8 and B8 is used as an example. Other compounds can be prepared by the methods in the following examples using the corresponding reactants.

[0051] Example 1: Preparation of compound A8:

[0052] The reaction route is shown below:

[0053]

[0054] Weigh 1.7 g of 1,2,4-triazole into a 50 mL round-bottom flask, add 15 mL of acetone, and after complete dissolution, add 3.5 g of 2-bromo-4'-methylacetophenone and 2.3 mL of triethylamine dissolved in 10 mL of acetone. Slowly add these to the reaction mixture under ice bath conditions (>5 min), and stir until the mixture is at room temperature for 5 h. After the reaction is complete, cool to room temperature, evaporate the solvent under reduced pressure, quench with water, extract with ethyl acetate, dry, and remove the solvent to obtain 3.0 g of crude product as a light yellow solid. Separate the crude product using silica gel column chromatography to obtain intermediate I, a yellow solid (1.86 g, 62%).

[0055] 0.94 g of phenol was placed in a 50 mL round-bottom flask, and 10 mL of N,N-dimethylformamide was added. The mixture was stirred until dissolved, and then 2.60 g of 1,4-dibromobutane was added sequentially. The mixture was stirred at room temperature, and the reaction was monitored by TLC until completion (reaction time 10 h). A large amount of water was added to the reaction system to remove the solvent N,N-dimethylformamide. The mixture was extracted with ethyl acetate, dried, and then distilled under reduced pressure to remove the ethyl acetate, yielding 2.24 g of crude product as a pale yellow solid. Separation was performed using silica gel column chromatography to obtain intermediate II, a yellow solid (1.52 g, 68%).

[0056] 1.3 g of intermediate I was dissolved in 5 mL of dimethyl sulfoxide, and 0.78 mL of 50% potassium hydroxide aqueous solution was added. The mixture was stirred until dissolved, and then 1.48 g of intermediate II was added. The mixture was stirred at room temperature for 8 h, and the reaction was monitored by TLC until completion. The mixture was quenched with 15 mL of water, extracted with 3 x 20 mL dichloromethane, and the organic phases were combined. The mixture was washed with 20 mL of water, dried, and the solvent was removed by evaporation under reduced pressure. The product was then dried over anhydrous sodium sulfate for 0.5 h, concentrated, and separated by silica gel column chromatography (using ethyl acetate and petroleum ether in a 1:5 volume ratio as solvents) to obtain the target product as a white solid (1.36 g, 60%).

[0057] Example 2, Preparation of compound B8:

[0058] The reaction route is shown below:

[0059]

[0060] Weigh 1.7 g of 1,2,4-triazole into a 50 mL round-bottom flask, add 15 mL of acetone, and after complete dissolution, add 3.5 g of 2-bromo-4'-methylacetophenone and 2.3 mL of triethylamine dissolved in 10 mL of acetone. Slowly add these to the reaction mixture under ice bath conditions (>5 min), and stir until the mixture is at room temperature for 6 h. After the reaction is complete, cool to room temperature, evaporate the solvent under reduced pressure, quench with water, extract with ethyl acetate, dry, and remove the solvent to obtain 3.0 g of crude product as a light yellow solid. Separate the crude product using silica gel column chromatography to obtain intermediate I' as a yellow solid (1.86 g, 62%).

[0061] 0.94 g of phenol was placed in a 50 mL round-bottom flask, and 10 mL of N,N-dimethylformamide was added. The mixture was stirred until dissolved, and then 2.78 g of 2,2'-dibromodiethyl ether was added sequentially. The mixture was stirred at room temperature, and the reaction was monitored by TLC until completion (12 h). A large amount of water was added to the reaction system to remove the N,N-dimethylformamide. The mixture was extracted with ethyl acetate, dried, and the solvent was removed to obtain 2.28 g of crude product, a pale yellow solid. Separation was performed using silica gel column chromatography to obtain intermediate II', a yellow solid (1.46 g, 64%).

[0062] 1.2 g of intermediate I' was dissolved in 5 mL of dimethyl sulfoxide, and 0.72 mL of 50% potassium hydroxide aqueous solution was added. The mixture was stirred until dissolved, and then 1.46 g of intermediate II' was added. The mixture was stirred at room temperature, and the reaction was monitored by TLC until completion (8 h). The reaction was quenched with 15 mL of water, extracted with 3 x 20 mL dichloromethane, and the organic phases were combined. The mixture was washed with 20 mL of water, dried, and the solvent was removed by evaporation under reduced pressure. The product was then dried over anhydrous sodium sulfate for 0.5 h, concentrated, and separated by silica gel column chromatography to obtain the target product as a white solid (1.17 g, 54%).

[0063] Other compounds mentioned above can be prepared using the same method as described above. The yields and appearances of some compounds are shown in Table 1.

[0064] Table 1. Number, yield and appearance of some compounds

[0065]

[0066]

[0067] Table 2. Nuclear magnetic resonance data of some compounds in Formula I.

[0068]

[0069]

[0070]

[0071]

[0072]

[0073]

[0074]

[0075]

[0076]

[0077] Example 3: The activity of compound I in the primary rosette branching of Arabidopsis thaliana was tested. The test method is as follows:

[0078] Arabidopsis seeds were disinfected with 1% sodium hypochlorite solution for 15 min, rinsed with sterile water, and sown on 1 / 2 MS medium (0.8% agar, 1% sucrose, and a certain concentration of the new compound). After vernalization at 4℃ for 3 days, the seeds were transferred to an artificial climate chamber and cultured in darkness (22℃) for 35 days. Whole plants were photographed, and the number of branches of primary rosette leaves longer than 5 mm was recorded. The results of all compound tests are shown in Tables 3 and 4.

[0079] Table 3. Screening of the activity of compound I on primary rosette branches in Arabidopsis thaliana.

[0080]

[0081] As shown in Table 3, the 2-phenoxy-2-(1H-1,2,4-triazole)-acetophenone compounds of this invention possess functions similar to strigolactone inhibitors, with higher activity than CK and TIS108. At a concentration of 3 μM, several compounds exhibited a greater promoting effect on the branching of primary rosettes in Arabidopsis thaliana than TIS108 at the same concentration. Furthermore, the activity of the B series compounds was significantly higher than that of the A series, and the B series compounds generally possessed certain branching-promoting activity. Among the two series of compounds, compounds A7 and B4, in particular, showed significant branching-promoting activity, achieving promotion rates of 189.5% and 221.4% for primary rosette branching in Arabidopsis thaliana, respectively, far exceeding the promoting effect of TIS108.

[0082] Table 4. Screening of the promoting effects of some active compounds on the initial rosette branching of Arabidopsis thaliana.

[0083]

[0084] As shown in Table 4, compound B4 exhibits superior branching-promoting activity compared to compounds A7 and TIS108 at different concentrations, and demonstrates good branching-promoting activity in the concentration range of 0.1-10 μM. The evaluation results of branching-promoting activity of primary rosette leaves in Arabidopsis thaliana show that this type of compound has activities related to strigolactone inhibitors, and at the same time, it has low design cost and high application value under the same conditions.

[0085] Example 4: The rice tillering activity of compound I was tested using the following method:

[0086] Rice seeds (Nipponbare) were surface-sterilized by washing with 1.5% sodium hypochlorite for 30 minutes, then thoroughly rinsed with sterile deionized water, and cultured in water at 30°C in the dark for 2 days. Pre-germinated seeds were then transferred to filter paper in 90mm petri dishes and cultured under fluorescent white light (130-180μm). 2 s -1 Rice seedlings were cultured at 30℃ for one week with a photoperiod of 16 hours light and 8 hours dark. Seven-day-old seedlings were then transferred to hydroponic containers containing nutrient solution and grown in an artificial climate chamber. Rice was treated with compound I at a concentration of 10 μM, with TIS108 used as a positive control. The compound was applied twice weekly for three weeks. After three weeks, the number of tillers per plant was measured, and the results of all compound tests are shown in Table 5.

[0087] Table 5 shows the promoting activity of compound I in rice tillering.

[0088]

[0089] As can be seen from Table 5, compound B4 can significantly promote rice tillering, further verifying that the target compound can promote branching of the aboveground parts in both the dicotyledonous model plant Arabidopsis thaliana and the monocotyledonous model plant rice, and has potential application value in agricultural production.

[0090] Example 5: Rice growth experiment

[0091] Rice seeds (Nipponbare) were surface-sterilized by washing with 1.5% sodium hypochlorite for 30 minutes, then thoroughly rinsed with sterile deionized water, and cultured in water at 30°C in the dark for 2 days. Pre-germinated seeds were then transferred to filter paper in 90mm petri dishes and cultured under fluorescent white light (130-180μm). 2 s -1 Rice seedlings were cultured at 30℃ for one week with a photoperiod of 16 hours of light and 8 hours of darkness. Seven-day-old seedlings were then transferred to hydroponic containers containing nutrient solution and grown in an artificial climate chamber. Rice was treated with compound I at a concentration of 10 μM, with TIS108 used as a positive control. The compound was applied twice weekly for a total of four weeks. After four weeks, plant height, fresh weight, and dry weight were measured. The results of all compound tests are shown in Table 6.

[0092] Table 6. Effects of some compounds at 10 μM on plant height and dry / fresh weight of rice

[0093]

[0094] Table 6 shows that the active compound B4 at 10 μM has a good regulatory effect on rice plant growth, inhibiting plant height and effectively increasing dry / fresh weight. Compound B4 can reduce rice plant height elongation by 11.8%, promote fresh weight increase by 35.5%, and promote dry weight increase by 14.4%. In contrast, TIS108 has a stronger inhibitory effect on rice plant height than B4 and leads to a reduction in rice dry matter. The results indicate that the side effects of B4 on rice growth and development stages are much weaker than those of A7 and TIS108, and it has greater application potential in agricultural production.

[0095] Example 6: Root growth experiment of wild-type Arabidopsis thaliana from Colombia:

[0096] Arabidopsis seeds were disinfected with 1% sodium hypochlorite solution for 15 min, rinsed with sterile water, and sown on 1 / 2 MS medium (0.8% agar, 1% sucrose, and new compound). After vernalization at 4℃ for 3 days, the seeds were transferred to an artificial climate chamber and cultured in the dark (22℃) for 7 days. The whole plant was photographed, and the length of the Arabidopsis taproot was measured using ImageJ software. The growth promotion rate of each compound and the control drug TIS108 on the Arabidopsis taproot was calculated using the formula: taproot growth promotion rate = (taper root length of drug group - taproot length of blank group) / taproot length of blank group × 100%. The results are shown in Table 7.

[0097] Table 7. Promotion rates of active compounds and control drugs on the primary root growth of Arabidopsis thaliana

[0098]

[0099] As shown in Table 7, the 2-phenoxy-2-(1H-1,2,4-triazole)-acetophenone compounds involved in this invention effectively promote the growth of Arabidopsis thaliana taproots, even at low concentrations (0.1-10 μM), achieving a 41.1% effect at 0.1 μM. At a concentration of 100 μM, the compounds inhibited the growth of Arabidopsis thaliana taproots (-73.7%), while the control drug TIS108 only showed root-promoting activity at a concentration of 0.1 μM (28.7%), and began to inhibit the growth of Arabidopsis thaliana taproots at a concentration of 10 μM (-25.7%). Therefore, the root-promoting activity of this type of compound is superior to that of TIS108. Furthermore, the synthesis cost of this type of compound is low, indicating that, under the same conditions, the compounds involved in this invention have higher utilization value.

[0100] The present invention has been described in detail above. Those skilled in the art will recognize that the invention can be practiced in a wide range of ways with equivalent parameters, concentrations, and conditions without departing from its spirit and scope, and without requiring unnecessary experiments. While specific embodiments have been provided, it should be understood that further modifications can be made to the invention. In summary, according to the principles of the invention, this application is intended to include any changes, uses, or improvements to the invention, including changes made using conventional techniques known in the art that depart from the scope disclosed herein.

Claims

1. Any one of the following compounds: 。 2. A method for preparing the compound of claim 1, comprising the following steps: 1) reacting a compound of formula II with 1 H -2,4-triazole under the action of an acid-binding agent to obtain a 2-(1 H -2,4-triazole)-acetophenone compound of formula III. wherein R in formula II, formula III 1 is selected from at least one of: methyl, methoxy; 2) The compound shown in Formula IV is reacted with phenol to obtain the compound shown in Formula V; wherein R 2 is n = 4 or R 2 is ; 3) Under the action of an acid-binding agent, the compound shown in Formula III is reacted with the compound shown in Formula V to obtain the compound of claim 1.

3. The method of claim 2, wherein: In step 1), the compound of formula II is reacted with 1 H - the molar ratio of 1,2,4-triazole is 1:1 to 2; The acid-binding agent is at least one of triethylamine and potassium carbonate; The reaction is carried out in a solvent: The solvent is selected from at least one of acetone and dichloromethane; The reaction was carried out at room temperature for 4-8 hours. In step 2), the molar ratio of the compound shown in formula IV to phenol is 1~2:

1. The reaction is carried out in a solvent; the solvent is at least one of ultra-dry dichloromethane and N,N-dimethylformamide. The reaction was carried out at room temperature for 6-12 hours. In step 3), the molar ratio of the compound shown in formula III to the compound shown in formula V is 1:1~2; The reaction is carried out in a solvent; the solvent is at least one of dichloromethane and dimethyl sulfoxide. The acid-binding agent is at least one of sodium hydroxide and potassium hydroxide; The reaction was carried out at room temperature for 6-8 hours.

4. The compound of claim 1 is used to prepare a plant growth regulator.

5. Use according to claim 4, characterized in that: The regulatory effects of the plant regulators include any one of the following: 1) Promotes branching development in plants; 2) Inhibits the germination of seeds of root-parasitic weeds; 3) Promotes the elongation of the hypocotyl in plant seedlings; 4) Promotes the elongation of the plant's taproot; 5) Inhibits the growth of root hairs in plants; 6) Delays the senescence of plant leaves.

6. Use according to claim 4 or 5, characterized in that: The plants are dicotyledons and monocotyledons; The root parasitic weeds mentioned are broomrape and strigophyte.

7. A plant growth regulator comprising any one of the compounds described in claim 1.

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