Isoquinoline sulfone compounds, methods of making and using the same
The electrochemical method for preparing isoquinoline sulfone compounds overcomes the limitations of isoquinoline derivatives and sulfone compounds in terms of biological activity and herbicide application, achieving effective inhibition of amide synthase (ALS) and significant herbicidal effect.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- JIANGXI NORMAL UNIV
- Filing Date
- 2023-09-25
- Publication Date
- 2026-04-24
AI Technical Summary
In the existing technology, isoquinoline derivatives and sulfone compounds have certain limitations in terms of biological activity and herbicide application, and their potential biological and herbicidal activities have not been fully explored.
Isoquinoline sulfone compounds are prepared by electrochemical reaction of isoquinoline NO compounds with sodium benzenesulfinate compounds in the presence of specific solvents and electrolytes. Using carbon rod and platinum sheet electrodes, the current and temperature are controlled to generate isoquinoline sulfone compounds with different substituents.
The prepared isoquinoline sulfone compounds showed good inhibition of amide synthase (ALS) and exhibited significant herbicidal activity. In particular, compound II-10 showed herbicidal activity similar to that of existing herbicides, indicating its potential application as a novel herbicide.
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Figure CN117304106B_ABST
Abstract
Description
Technical Field
[0001] This invention relates to organic chemical synthesis, specifically to isoquinoline sulfone compounds, their preparation methods, and applications. Background Technology
[0002] Isoquinoline derivatives are widely used in synthetic chemistry and medicinal chemistry. [1-3] Many isoquinoline derivatives possess excellent biological activity, with isoquinoline alkaloids being a typical example. Isoquinoline alkaloids are a class of natural products of significant importance in modern biomedical research and drug development. Currently, isoquinoline alkaloids constitute the largest known class of alkaloids. Due to their excellent biological activity, isoquinoline alkaloids have been applied in anti-inflammatory and antibacterial, analgesic and antitussive, anticancer and antitumor, antiarrhythmic, antiplatelet aggregation, cardiovascular protection, and immune regulation applications. They are even being explored for treating some intractable diseases. For example, Narciclasine... [4] Lamellarin is an alkaloid isolated from the secretions of the bulbs of the daffodil multiflora. It can effectively inhibit protein synthesis in ascites cells and has certain antiviral and antitumor effects. [5] Saframycin is a class of alkaloids isolated from marine mollusks. It exhibits good activity in inhibiting tumor cell proliferation and reversing ρ-glycoprotein-mediated multidrug resistance, showing potential as an anti-tumor drug candidate. [6] These are bioactive substances that act on DNA or DNA synthesis, and were first discovered in actinomycetes (as shown in the following formula). Furthermore, recent patents have reported that isoquinoline alkaloids possess herbicidal activity. [7] .
[0003]
[0004] Similarly, sulfones are an important class of compounds in organic chemistry. This is mainly due to the diverse activities of sulfones. Sulfones have been widely used in research fields such as materials science, biology, pesticides, and pharmaceuticals. Among their applications in pesticides are sulfonylurea herbicides and sulfonamide herbicides, demonstrating the important role of sulfones in herbicides. Several commercially available sulfonylurea and sulfonamide herbicides are shown in the following formulas:
[0005]
[0006] Existing technical documents:
[0007] [1]Diamond A.Desgagné-Penix I.Metabolic engineering for theproduction of plant isoquinoline alkaloids[J].Plant Biotechnol.J,2016,14(6):1319-1328;
[0008] [2]Zhao Y H,Li Y,Guo T,Tang Z,Xie W,Zhao G.Selective synthesis ofpyrazolo[5,1-a]isoquinolines via 1,3-dipolar cycloaddition reaction[J].Tetrahedron Letters,2016,57(21),2257-2261;
[0009] [3]Mortier J,Frederick R,Ganeff C,Remouchamps C,etal.Pyrazolo[4,3-c]isoquinolines as potential inhibitors of NF-κB activation[J].BiochemicalPharmacology,2010,79(10),1462-1472;
[0010] [4]Ingrassia L,Lefranc F,Dewelle J,Pottier L,etal.Structure-ActivityRelationship Analysis of Novel Derivatives of Narciclasine(an AmaryllidaceaeIsocarbostyril Derivative)as Potential Anticancer Agents[J].Journal ofMedicinal Chemistry,2009,52(4),1100-1114;
[0011] [5]Bailly C,etal.a family of anticancer marine pyrrole alkaloids[J].Current medicinal chemistry.Anti-cancer agents,2004,4(4),363-78;
[0012] [6] Lown JW, Joshua AV, Lee J S. Molecular mechanisms of binding and single-strand scission of DNA by the antitumor antibiotics saframycins Aand C[J]. Biochemistry, 1982, 21(3), 419-428;
[0013] [7] Zhou Lijuan, Huang Jiguang, Tian Yanqin. Application of a class of isoquinoline alkaloids as herbicides [P]. Chinese Patent, 107950546. 2018-04-24;
[0014] [8] Chen Yifeng, Li Yiwei. Establishment of a simple method for determining acetolactate synthase activity [J]. Journal of Jiangxi Agricultural University, 1996, 18(2): 213-218. Summary of the Invention
[0015] The purpose of this invention is to provide an isoquinoline sulfone compound, its preparation method, and its application.
[0016] The isoquinoline sulfone compound has the structure shown in formula (I) or formula (II):
[0017]
[0018] In the formula, R1 and R2 are independently selected from hydrogen, C1-C18 alkyl groups, C1-C18 alkoxy groups, halogens, and nitro groups. The substitution position of R1 is any position on the benzene ring of the isoquinoline and any position on the other two carbons of the nitrogen heterocycle, and the substitution position of R2 is any position on the benzene ring of sodium benzenesulfinate compounds. That is, in formula (I), R1 is attached to carbon atoms 3, 4, 5, 6, 7, or 8 of the isoquinoline, and R2 is attached to carbon atoms 2, 3, or 4 of the benzene ring; in formula (II), R1 is attached to carbon atoms 1, 4, 5, 6, 7, or 8 of the isoquinoline, and R2 is attached to carbon atoms 2, 3, or 4 of the benzene ring.
[0019] In some preferred embodiments, R1 and R2 are independently selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, fluorine, chlorine, bromine, iodine, and nitro.
[0020] In some preferred embodiments, the isoquinoline sulfone compound has a structure represented by any of the following formulas:
[0021]
[0022]
[0023] The preparation method of the isoquinoline sulfone compound includes the following steps:
[0024] The isoquinoline NO compound shown in formula (III) and the sodium benzenesulfinate compound shown in formula (IV) are reacted to obtain the isoquinoline sulfone compound;
[0025]
[0026] In the formula, R1 and R2 are independently selected from hydrogen, C1-C18 alkyl, C1-C18 alkoxy, halogen, and nitro.
[0027] In some preferred embodiments, the isoquinoline NO compounds represented by formula (Ⅲ) have a structure represented by any of the following formulas:
[0028]
[0029] The sodium benzenesulfinate compound represented by formula (Ⅳ) has a structure represented by any of the following formulas:
[0030]
[0031] In some preferred embodiments, the reaction is carried out in a solvent; the solvent is acetonitrile, water and acetic acid, with an optimal volume ratio of 8:1:0.3.
[0032] In some preferred embodiments, the reaction is carried out under energized conditions; these energized conditions may refer to the addition of an electrolyte to the solvent and the insertion of an electrode to form a current path. The electrode is C / Pt, C / Ni, or Pt / Pt, with C / Pt being the optimal electrode. The electrolyte is sodium iodide (NaI), and the current in the current path is 12 mA.
[0033] In some preferred embodiments, the reaction temperature is 30–40°C and the reaction time is 1–10 h.
[0034] The isoquinoline compounds can be applied in materials, biology, pesticides, and pharmaceuticals, for example, in the preparation of herbicides. Therefore, the present invention also provides a herbicide comprising the isoquinoline compounds.
[0035] Since isoquinoline sulfone compounds belong to both isoquinoline derivatives and sulfone compounds, and both isoquinoline derivatives and sulfone compounds exhibit good biological activity, it can be inferred that isoquinoline sulfone compounds should also possess good biological activity. This invention investigated the herbicidal activity of this type of isoquinoline sulfone compound, and the study found that these compounds possess certain herbicidal activity and have potential applications in the development of novel herbicides. Attached Figure Description
[0036] The specific embodiments of the present invention will be further described in detail below with reference to the accompanying drawings.
[0037] Figure 1 The hydrogen spectrum of the product 1-benzenesulfonyl isoquinoline in Example 1 of this invention.
[0038] Figure 2 This is the carbon spectrum of 1-benzenesulfonyl isoquinoline, the product in Example 1 of this invention.
[0039] Figure 3 The hydrogen spectrum of the product 3-benzenesulfonyl isoquinoline in Example 1 of this invention.
[0040] Figure 4 This is the carbon spectrum of the product 3-benzenesulfonyl isoquinoline in Example 1 of the present invention. Detailed Implementation
[0041] To better understand the above-described objects, features, and advantages of the present invention, the invention will be further described in detail below with reference to the accompanying drawings and specific embodiments. Many specific details are set forth in the following description to provide a thorough understanding of the invention; however, the invention may be practiced in other ways different from those described herein, and therefore, the invention is not limited to the specific embodiments disclosed below.
[0042] The inventors discovered that, using a carbon rod as the positive electrode, a platinum sheet as the negative electrode, and sodium iodide as the electrolyte, under certain current range, temperature, and specific reaction conditions, the isoquinoline NO compounds represented by formula (III) and the sodium benzenesulfinate compounds represented by formula (IV) react for 6 hours to obtain a series of isoquinoline sulfone compounds represented by formula (I) or formula (II).
[0043]
[0044] In the formula, R1 and R2 are independently selected from hydrogen, C1-C18 alkyl, C1-C18 alkoxy, halogen, and nitro.
[0045] The following are some typical examples.
[0046] Example 1: Synthesis of 1-benzenesulfonylisoquinoline (I-1) and 3-benzenesulfonylisoquinoline (II-1)
[0047] A carbon and platinum electrode was installed on a 25 ml dry three-necked flask. Then, 0.5 mmol of isoquinoline NO compound, 1.25 mmol of sodium benzenesulfinate, 0.4 mmol of sodium iodide, and a magnetic electrode were added to the flask. The flask was then sealed, evacuated, and purged with N2 gas. This process was repeated three times. Next, 0.3 ml of acetic acid, 1.0 ml of water, and 8.0 ml of acetonitrile were added to the flask, and the flask was sealed again. The flask was then placed in an electrochemical reactor with stirring. The current was set to 12 mA, the temperature to 35 °C, and the reaction was maintained under these conditions for 6 hours. The flask was then removed, and a suitable amount of saturated sodium bicarbonate aqueous solution was added. The mixture was extracted three times with dichloromethane. The dichloromethane phase was collected, and the fractions were separated by vacuum distillation and column chromatography to obtain 66 mg of 1-benzenesulfonyl isoquinoline (yield 49%) and 57 mg of 3-benzenesulfonyl isoquinoline compound (yield 43%).
[0048] The target product is:
[0049]
[0050] The products were identified as 1-benzenesulfonyl isoquinoline (I-1) and 3-benzenesulfonyl isoquinoline (II-1) by proton and carbon NMR spectroscopy. The proton and carbon NMR spectra of 1-benzenesulfonyl isoquinoline are shown below. Figure 1 Hejian Figure 2 The 1H and 1C spectra of 3-benzenesulfonylisoquinoline are shown below. Figure 3 Hejian Figure 4 The structural characterization data are as follows:
[0051]
[0052] 1 H NMR (400MHz, CDCl3) δ9.21–9.12(m,1H),8.43(d,J=5.4Hz,1H),8.10(d,J=7.5Hz,2H),7.9 7–7.87(m,1H),7.78(dd,J=9.3,5.0Hz,3H),7.65(t,J=7.4Hz,1H),7.56(t,J=7.6Hz,2H). 13 C NMR (100MHz, CDCl3) δ157.18,140.68,139.23,137.91,133.81,131.29,129.41,129.34,129.01,127.70,125.40,125.19,124.48.
[0053]
[0054] 1H NMR(400MHz, CDCl3)δ9.23(s,1H),8.66(s,1H),8.16–8.09(m,2H),8.02(dd,J=7.9 ,3.8Hz,2H),7.87–7.81(m,1H),7.81–7.75(m,1H),7.58(m,1H),7.55–7.49(m,2H). 13 CNMR (100MHz, CDCl3) δ153.84,152.10,139.47,135.40,133.67,132.11,130.47,129.54,129.18,128.91,128.30,127.95,121.37.
[0055] Example 2: Synthesis of 5-chloro-1-benzenesulfonyl isoquinoline and 5-chloro-3-benzenesulfonyl isoquinoline
[0056] A carbon and platinum electrode was installed on a 25 ml dry three-necked flask. Then, 0.5 mmol of 5-chloro-isoquinoline NO compound, 1.25 mmol of sodium benzenesulfinate, 0.4 mmol of sodium iodide, and a magnetic stir bar were added to the flask. The flask was then sealed, evacuated, and purged with N2 gas. This process was repeated three times. Next, 0.3 ml of acetic acid, 1.0 ml of water, and 8.0 ml of acetonitrile were added to the flask, and the flask was sealed again. The flask was then placed in an electrochemical reactor with stirring. The current was set to 12 mA, the temperature to 35 °C, and the reaction was maintained under these conditions for 6 hours. The flask was then removed, and a suitable amount of saturated sodium bicarbonate aqueous solution was added. The mixture was extracted three times with dichloromethane. The dichloromethane phase was collected, and the fractions were separated by vacuum distillation and column chromatography to obtain 70 mg of 5-chloro-1-benzenesulfonylisoquinoline (yield 46%) and 52 mg of 5-chloro-3-benzenesulfonylisoquinoline compound (yield 34%).
[0057] The structural formulas of 5-chloro-1-benzenesulfonyl isoquinoline (I-2) and 5-chloro-3-benzenesulfonyl isoquinoline (II-2) are as follows:
[0058]
[0059] Example 3: Synthesis of 6-chloro-1-benzenesulfonylisoquinoline (I-3) and 6-chloro-3-benzenesulfonylisoquinoline (II-3)
[0060] A carbon and platinum electrode was installed on a 25 ml dry three-necked flask. Then, 0.5 mmol of 6-chloro-isoquinoline NO compound, 1.25 mmol of sodium benzenesulfinate, 0.4 mmol of sodium iodide, and a magnetic stir bar were added to the flask. The flask was then sealed, evacuated, and purged with N2 gas. This process was repeated three times. Next, 0.3 ml of acetic acid, 1.0 ml of water, and 8.0 ml of acetonitrile were added to the flask, and the flask was sealed again. The flask was then placed in an electrochemical reactor with stirring. The current was set to 12 mA, the temperature to 35 °C, and the reaction was maintained under these conditions for 6 hours. The flask was then removed, and a suitable amount of saturated sodium bicarbonate aqueous solution was added. The mixture was extracted three times with dichloromethane. The dichloromethane phase was collected, and the fractions were separated by vacuum distillation and column chromatography to obtain 59 mg of 6-chloro-1-benzenesulfonylisoquinoline (yield 39%) and 56 mg of 6-chloro-3-benzenesulfonylisoquinoline compound (yield 37%).
[0061] The structural formulas of 6-chloro-1-benzenesulfonyl isoquinoline (I-3) and 6-chloro-3-benzenesulfonyl isoquinoline (II-3) are as follows:
[0062]
[0063] Example 4: Synthesis of 6-methyl-1-benzenesulfonylisoquinoline (I-4) and 6-methyl-3-benzenesulfonylisoquinoline (II-4)
[0064] A carbon electrode and a platinum electrode were installed on a 25 ml dry three-necked flask. Then, 0.5 mmol of 6-methyl-isoquinoline NO compound, 1.25 mmol of sodium benzenesulfinate, 0.4 mmol of sodium iodide, and a magnetic stir bar were added to the flask. The flask was then sealed, evacuated, and filled with N2 gas. This process was repeated three times. Next, 0.3 ml of acetic acid, 1.0 ml of water, and 8.0 ml of acetonitrile were added to the flask, and it was sealed again. The three-necked flask was then placed in an electro-reaction apparatus and stirred. The current was set to 12 mA and the temperature to 35 °C. The reaction was maintained under these conditions for 6 hours. The flask was then removed, and an appropriate amount of saturated sodium bicarbonate aqueous solution was added to neutralize the acetic acid in the reaction solution. The mixture was extracted three times with dichloromethane, and the dichloromethane phase was collected. The phases were then separated by vacuum distillation and column chromatography to obtain 40 mg of 6-methyl-1-benzenesulfonylisoquinoline (yield 28%) and 85 mg of 6-methyl-3-benzenesulfonylisoquinoline compound (yield 60%).
[0065] The structural formulas of 6-chloro-1-benzenesulfonyl isoquinoline (I-4) and 6-chloro-3-benzenesulfonyl isoquinoline (II-4) are as follows:
[0066]
[0067] Example 5: Synthesis of 4-methyl-1-benzenesulfonylisoquinoline (I-6)
[0068] A carbon and platinum electrode was installed on a 25 ml dry three-necked flask. Then, 0.5 mmol of 4-methyl-isoquinoline NO compound, 1.25 mmol of sodium benzenesulfinate, 0.4 mmol of sodium iodide, and a magnetic stir bar were added to the flask. The flask was then sealed, evacuated, and purged with N2 gas. This process was repeated three times. Next, 0.3 ml of acetic acid, 1.0 ml of water, and 8.0 ml of acetonitrile were added to the flask, and the flask was sealed again. The flask was then placed in an electrochemical reactor with stirring. The current was set to 12 mA, the temperature to 35 °C, and the reaction was maintained under these conditions for 6 hours. Afterward, the flask was removed, and a suitable amount of saturated sodium bicarbonate aqueous solution was added to neutralize the acetic acid in the reaction solution. The mixture was extracted three times with dichloromethane, and the dichloromethane phase was collected. The solution was then separated by vacuum distillation and column chromatography to obtain 96 mg of 4-methyl-1-benzenesulfonylisoquinoline compound (yield 68%).
[0069] The structural formula of 4-methyl-1-benzenesulfonylisoquinoline (I-6) is:
[0070]
[0071] Example 6: Synthesis of 3-methyl-1-benzenesulfonylisoquinoline (I-7)
[0072] A carbon and platinum electrode was installed on a dry 25 ml three-necked flask. Then, 0.5 mmol of 3-methyl-isoquinoline NO compound, 1.25 mmol of sodium benzenesulfinate, 0.4 mmol of sodium iodide, and a magnetic stir bar were added to the flask. The flask was then sealed, evacuated, and purged with N2 gas. This process was repeated three times. Next, 0.3 ml of acetic acid, 1.0 ml of water, and 8.0 ml of acetonitrile were added to the flask, and the flask was sealed again. The flask was then placed in an electrochemical reactor with stirring. The current was set to 12 mA, the temperature to 35 °C, and the reaction was maintained under these conditions for 6 hours. The flask was then removed, and a suitable amount of saturated sodium bicarbonate aqueous solution was added to neutralize the acetic acid in the reaction solution. The mixture was extracted three times with dichloromethane, and the dichloromethane phase was collected. The solution was then separated by vacuum distillation and column chromatography to obtain 106 mg of 3-methyl-1-benzenesulfonylisoquinoline compound (75% yield).
[0073] The structural formula of 3-methyl-1-benzenesulfonylisoquinoline (I-7) is:
[0074]
[0075] Example 7: Synthesis of 4-bromo-1-benzenesulfonylisoquinoline (I-8)
[0076] A carbon and platinum electrode was installed on a dry 25 ml three-necked flask. Then, 0.5 mmol of 4-bromo-isoquinoline NO compound, 1.25 mmol of sodium benzenesulfinate, 0.4 mmol of sodium iodide, and a magnetic stir bar were added to the flask. The flask was then sealed, evacuated, and purged with N2 gas. This process was repeated three times. Next, 0.3 ml of acetic acid, 1.0 ml of water, and 8.0 ml of acetonitrile were added to the flask, and the flask was sealed again. The flask was then placed in an electrochemical reactor with stirring. The current was set to 12 mA, the temperature to 35 °C, and the reaction was maintained under these conditions for 6 hours. Afterward, the flask was removed, and a suitable amount of saturated sodium bicarbonate aqueous solution was added to neutralize the acetic acid in the reaction solution. The mixture was extracted three times with dichloromethane, and the dichloromethane phase was collected. The solution was then separated by vacuum distillation and column chromatography to obtain 125 mg of 4-bromo-1-benzenesulfonylisoquinoline compound (yield 72%).
[0077] The structural formula of 4-bromo-1-benzenesulfonyl isoquinoline (I-8) is:
[0078]
[0079] Example 8: Synthesis of 1-methyl-3-benzenesulfonylisoquinoline (II-6)
[0080] A carbon and platinum electrode was installed on a dry 25 ml three-necked flask. Then, 0.5 mmol of 1-methyl-isoquinoline NO compound, 1.25 mmol of sodium benzenesulfinate, 0.4 mmol of sodium iodide, and a magnetic stir bar were added to the flask. The flask was then sealed, evacuated, and purged with N2 gas. This process was repeated three times. Next, 0.3 ml of acetic acid, 1.0 ml of water, and 8.0 ml of acetonitrile were added to the flask, and the flask was sealed again. The flask was then placed in an electrochemical reactor with stirring. The current was set to 12 mA, the temperature to 35 °C, and the reaction was maintained under these conditions for 6 hours. The flask was then removed, and a suitable amount of saturated sodium bicarbonate aqueous solution was added to neutralize the acetic acid in the reaction solution. The mixture was extracted three times with dichloromethane, and the dichloromethane phase was collected. The solution was then separated by vacuum distillation and column chromatography to obtain 112 mg of 1-methyl-3-benzenesulfonylisoquinoline compound (yield 79%).
[0081] The structural formula of 1-methyl-3-benzenesulfonylisoquinoline (II-6) is:
[0082]
[0083] Example 9: Synthesis of 1-p-fluorobenzenesulfonyl isoquinoline (I-9) and 3-p-fluorobenzenesulfonyl isoquinoline (II-7)
[0084] A carbon and platinum electrode was installed on a 25 ml dry three-necked flask. Then, 0.5 mmol of isoquinoline NO compound, 1.25 mmol of sodium p-fluorobenzenesulfinate, 0.4 mmol of sodium iodide, and a magnetic electrode were added to the flask. The flask was then sealed, evacuated, and purged with N2 gas. This process was repeated three times. Next, 0.3 ml of acetic acid, 1.0 ml of water, and 8.0 ml of acetonitrile were added to the flask, and the flask was sealed again. The flask was then placed in an electrochemical reactor with stirring. The current was set to 12 mA, the temperature to 35 °C, and the reaction was maintained under these conditions for 6 hours. The flask was then removed, and a suitable amount of saturated sodium bicarbonate aqueous solution was added to neutralize the acetic acid in the reaction solution. The mixture was extracted three times with dichloromethane, and the dichloromethane phase was collected. The phase was then separated by vacuum distillation and column chromatography to obtain 80 mg of 1-p-fluorobenzenesulfonyl isoquinoline (yield 56%) and 39 mg of 3-p-fluorobenzenesulfonyl isoquinoline (yield 27%).
[0085] The structures of 1-p-fluorobenzenesulfonyl isoquinoline (I-9) and 3-p-fluorobenzenesulfonyl isoquinoline (II-7) are as follows:
[0086]
[0087] Example 10: Synthesis of 1-p-chlorobenzenesulfonyl isoquinoline (I-10) and 3-p-chlorobenzenesulfonyl isoquinoline (II-8)
[0088] A carbon and platinum electrode was installed on a 25 ml dry three-necked flask. Then, 0.5 mmol of isoquinoline NO compound, 1.25 mmol of sodium p-chlorobenzenesulfinate, 0.4 mmol of sodium iodide, and a magnetic electrode were added to the flask. The flask was then sealed, evacuated, and purged with N2 gas. This process was repeated three times. Next, 0.3 ml of acetic acid, 1.0 ml of water, and 8.0 ml of acetonitrile were added to the flask, and the flask was sealed again. The flask was then placed in an electrochemical reactor with stirring. The current was set to 12 mA, the temperature to 35 °C, and the reaction was maintained under these conditions for 6 hours. The flask was then removed, and a suitable amount of saturated sodium bicarbonate solution was added to neutralize the acetic acid in the reaction solution. The mixture was extracted three times with dichloromethane, and the dichloromethane phase was collected. The phase was then separated by vacuum distillation and column chromatography to obtain 61 mg of 1-p-chlorobenzenesulfonyl isoquinoline (yield 40%) and 74 mg of 3-p-chlorobenzenesulfonyl isoquinoline (yield 49%).
[0089] The structures of 1-p-chlorobenzenesulfonyl isoquinoline (I-10) and 3-p-chlorobenzenesulfonyl isoquinoline (II-8) are as follows:
[0090]
[0091] The preparation of other products (I-5, I-11, I-12 and II-9, II-10) is similar to that in Examples 1-10 above, and will not be described again here. Obviously, the above embodiments of the present invention are merely examples to clearly illustrate the preparation of isoquinoline sulfone compounds in the present invention, and are not intended to limit the implementation of the present invention. For those skilled in the art, other variations or modifications can be made based on the above description. It is impossible to exhaustively list all embodiments here. All obvious variations or modifications derived from the technical solutions of the present invention are still within the protection scope of the present invention.
[0092] Since the target enzymes of sulfonylurea and sulfonamide herbicides are ALS, the inventors used commercially available herbicides pyrimethanil and chlorpyrifos as control drugs, employing the creatine-naphthol colorimetric method. [8] The ALS inhibition experiments were conducted on the compounds prepared above, and the results are shown in Table 1.
[0093] Table 1. Inhibition rate of the compounds prepared in this invention against ALS
[0094]
[0095] --: Inhibition rate <1%
[0096] Table 1 shows that compounds I-2, II-3, I-7, II-9, and II-10 exhibited inhibition rates of 52%, 45%, 51%, 46%, and 47% against ALS, respectively, while the commercially available herbicides pyrazosulfuron and chlorpyrifos showed inhibition rates of 44% and 41% against ALS, respectively. Therefore, the inhibitory activity of these five isoquinoline sulfone compounds against ALS is comparable to that of the commercially available herbicides pyrazosulfuron and chlorpyrifos, indicating that these five isoquinoline sulfone compounds possess good inhibitory activity against ALS.
[0097] To further verify that these five compounds have certain herbicidal activity, the inventors used pyrazosulfuron and chlorpyrifos as control samples and tested the inhibitory effects of these five compounds on the root and stem growth of barnyard grass and sorghum (monocotyledonous plants) and cucumber and radish (dicotyledonous plants). The experimental results are shown in Tables 2 and 3.
[0098] Table 2. Effects of five isoquinoline sulfonates on the roots and stems of barnyard grass and sorghum.
[0099]
[0100] Table 3. Effects of five isoquinoline sulfones on the roots and stems of cucumber and radish.
[0101]
[0102]
[0103] As shown in Tables 2 and 3, these five isoquinoline sulfone compounds all have a certain inhibitory effect on the root and stem growth of barnyard grass and sorghum (monocotyledonous plants) and cucumber and radish (dicotyledonous plants). Moreover, the inhibitory effect of compound II-10 on the root and stem growth of barnyard grass and sorghum (monocotyledonous plants) is comparable to that of the commercially available herbicides pyrimethanil and chlorpyrifos on the root and stem growth of barnyard grass and sorghum.
[0104] In summary, this invention provides a method for preparing a class of isoquinoline sulfone compounds, and a series of isoquinoline sulfone compounds were prepared using this method. Then, ALS activity inhibition tests were conducted on these isoquinoline sulfone compounds, revealing that five compounds exhibited good inhibitory effects on ALS activity. Subsequently, the herbicidal activity of these five compounds was tested, and the results showed that these five compounds possessed certain herbicidal activity against both monocots and dicots. In particular, compound II-10 showed herbicidal activity comparable to that of commercially available herbicides pyrimethanil and chlorpyrifos. Through these studies, it was found that these isoquinoline sulfone compounds have potential applications in the development of novel herbicides.
Claims
1. An isoquinoline sulfone compound, characterized in that, The isoquinoline sulfone compound has a structure shown in any of the following formulas: 。 2. The application of the isoquinoline sulfone compound according to claim 1 in the preparation of herbicides.
3. A herbicide, characterized in that, The herbicide comprises the isoquinoline sulfone compound according to claim 1.