2 (5H)-furanone derivative, preparation method thereof and application of 2 (5H)-furanone derivative as biocide

Abstract

The invention discloses a 2 (5H)-furanone derivative, a preparation method thereof and application of the 2 (5H)-furanone derivative as a biocide. The invention provides an effective means for synthesizing the 2 (5H)-furanone derivative, when the 2 (5H)-furanone derivative is prepared, the reaction conditions are green and metal-free, the operation is easy at room temperature, and the large-scale production is facilitated; according to the invention, the target product can be obtained with high yield and high selectivity. The 2 (5H)-furanone derivative disclosed by the invention has good inhibitory activity on the mycelial growth rate of plant-derived germs (such as tomato early blight, strawberry grey mould and wheat gibberellic mildew), has bactericidal activity and can be used as a pesticide.

Description

Technical Field

[0001] The present invention belongs to the technical field of the preparation of organic compounds, and particularly relates to a preparation method of a 2(5H)-furanone derivative and its application as a biocide. Background Art

[0002] 2(5H)-furanone derivatives, also known as γ-butenolide derivatives. This type of structural skeleton is mainly used in medicine for the development of drugs such as antihypertensive, antibacterial, and anticancer drugs for the human body (Suélen Karine Sartori, Marisa AlvesNogueira Diaz, Gaspar Diaz-Munoz. Lactones: Classification, Synthesis,Biological Activities, and Industrial Applications. Tetrahedron . 2021, 84 ,132001.). In addition, 2(5H)-furanone compounds are also widely used in the fields of natural products, cosmetics, food, and pesticides (1) Amandine L. Flourat, Arnaud Haudrechy, Florent Allais, Jean-HuguesRenault. (S)-γ-Hydroxymethyl-α,β-butenolide, a Valuable Chiral Synthon:Syntheses, Reactivity, and Applications. Org. Process Res. Dev . 2020, 24 , 615(2) Krishnaji Tadiparthi, Swathy Venkatesh. Synthetic Approaches towardButenolide-Containing Natural Products. Therefore, the research on the construction of the 2(5H)-furanone derivative skeleton is one of the important research directions in organic chemistry.

[0003] Traditionally, 2(5H)-furanone compounds are mainly synthesized from L-glutamic acid, D-nucleic acid lactone, and D-mannitol through multiple steps of reaction. To improve atom economy and yield, recent methodological research has mainly used substituted allene compounds as raw materials and achieved the one-step synthesis of the 2(5H)-furanone structure through transition metal-catalyzed methods (D. Ravi Sankar, Mohan Neetha, Gopinathan Anilkumar. Gold-Catalyzed Lactone Synthesis: Advancements and Insights. Chem. Rec. 2024, 24 , e202400071.). However, such methods generally require the synthesis of complex and expensive transition metal catalysts (such as Au salts and Ag salts), which limits the large-scale promotion and industrial application of such methods. Therefore, it is of great significance to develop a method with simple operation, mild reaction conditions, meeting the requirements of green chemistry, and enabling the efficient synthesis of 2(5H)-furanone derivatives from allene compounds. Summary of the Invention

[0004] The object of the present invention is to provide a 2(5H)-furanone derivative and its preparation method, which have the advantages of mild reaction conditions, high selectivity, green and environmentally friendly reaction process, and high yield. The 2(5H)-furanone derivative of the present invention has good inhibitory activity against the mycelial growth rate of phytopathogenic bacteria (such as Alternaria solani, Botrytis cinerea, Gibberella zeae), has bactericidal activity, and can be used as a pesticide.

[0005] To achieve the above object of the invention, the technical solution adopted by the present invention is as follows.

[0006] A preparation method of a 2(5H)-furanone derivative, comprising the following steps: using a substituted allene and a disubstituted aryl disulfide as raw materials to react to prepare a 2(5H)-furanone derivative.

[0007] In the present invention, the reaction is carried out in the presence of an oxidant, molecular sieve, and solvent.

[0008] Preferably, the oxidant is selected from one or more of pyridinium chlorochromate, tert-butyl hydroperoxide, di-tert-butyl peroxide, tert-butyl peroxybenzoate, and m-chloroperoxybenzoic acid.

[0009] In the present invention, the molar ratio of the substituted allene, the disubstituted aryl disulfide, and the oxidant is 1∶(0.5 - 2)∶(1 - 3).

[0010] In the present invention, the reaction is carried out under light; the light includes one of blue light, green light, and white light.

[0011] In the present invention, the reaction is carried out at 10 to 50 °C for 5 to 50 hours. In the present invention, the substituted allene is represented by the following general chemical structure formula: ; The disubstituted aryl disulfide is represented by the following general chemical structure formula: ; The 2(5H)-furanone derivative is a 3-(diarylphosphinyloxy)-4-arylthio-5-aryl-alkyl-2(5H)-furanone derivative, and its general chemical structure formula is as follows: ; wherein R 1 , R 2 are independently selected from one of hydrogen, alkyl, alkoxy, halogen, haloalkoxy, and nitro; R 3 is selected from one of hydrogen, alkyl, alkoxy, halogen, ester group, nitro, and haloalkyl; n is 0 to 10.

[0012] In the present invention, in the alkyl, alkoxy, haloalkoxy, and haloalkyl, the number of carbon atoms is independently selected from 1 to 10; n is 0 to 5.

[0013] Preferably, the haloalkoxy is trifluoromethoxy; n is 0, 1, or 2.

[0014] The present invention discloses a method for plant sterilization, which includes the following steps: applying a reagent containing the above-mentioned 2(5H)-furanone derivative to a plant to achieve plant sterilization. The 2(5H)-furanone derivative of the present invention has good inhibitory activity against the mycelial growth rate of plant-derived pathogens (such as Alternaria solani, Botrytis cinerea, and Gibberella zeae), has bactericidal activity, and can be used as a pesticide. When the derivative of the present invention is used as a pesticide, the specific application method is a conventional technique.

[0015] The present invention discloses the use of the above-mentioned 2(5H)-furanone derivative as a biocide or in the preparation of a biocide.

[0016] A drug, the active ingredient of which includes the above-mentioned 2(5H)-furanone derivative.

[0017] In the present invention, the drug is preferably an antibacterial drug, and more preferably a pesticide.

[0018] The present invention discloses an antibacterial method, which uses the above-mentioned 2(5H)-furanone derivative as a drug to achieve antibacterial.

[0019] In the present invention, the above-mentioned 2(5H)-furanone derivative is placed in a bacteria-containing environment to achieve antibacterial.

[0020] As a specific technical solution, the present invention discloses a method for preparing 2(5H)-furanone derivatives, comprising the following steps: dissolving a substituted allene, a disubstituted aryl disulfide, an oxidant, and a molecular sieve in a solvent, and reacting at room temperature under the illumination of an LED strip light to selectively obtain 3-(diarylphosphinyloxy)-4-arylthio-5-aryl-alkyl-2(5H)-furanone derivatives.

[0021] Preferably, the substituted allene is selected from: (1-hydroxy-4-phenyl-4-methyl-2-diphenyloxyphosphine)-yl-2,3-allene, (1-hydroxy-4-phenyl-4-methyl-2-bis(2-chlorophenyl)oxyphosphine)-yl-2,3-allene, (1-hydroxy-4-(4-methoxyphenyl)-4-methyl-2-bis(3-chlorophenyl)oxyphosphine)-yl-2,3-allene, (1-hydroxy-4-(4-chlorophenyl)-4-methyl-2-bis(4-chlorophenyl)oxyphosphine)-yl-2,3-allene, (1-hydroxy-4-(4-ethylcarboxyphenyl)-4-methyl-2-bis(4-fluorophenyl)oxyphosphine)-yl-2,3-allene, (1-hydroxy-4-(4-nitrophenyl)-4-methyl-2-bis(4-bromophenyl)oxyphosphine)-yl-2,3-allene, (1-hydroxy-4-phenyl-4-methyl-2-bis(4-chlorophenyl)oxyphosphine)-yl-2,3-allene, (1-hydroxy-4-phenyl-4-methyl-2-bis(4-methoxyphenyl)oxyphosphine)-yl-2,3-allene, (1-hydroxy-4-phenyl-4-methyl-2-bis(4-trifluoromethoxyphenyl)oxyphosphine)-yl-2,3-allene, (1-hydroxy-4-phenyl-4-methyl-2-bis(4-nitrophenyl)oxyphosphine)-yl-2,3-allene, (1-hydroxy-4-phenyl-4-ethyl-2-diphenyloxyphosphine)-yl-2,3-allene, (1-hydroxy-4-phenyl-4-propyl-2-diphenyloxyphosphine)-yl-2,3-allene.

[0022] Preferably, the disubstituted aryl disulfide is selected from: diphenyl disulfide, bis(4-methylphenyl) disulfide, bis(4-methoxyphenyl) disulfide, bis(4-fluorophenyl) disulfide, bis(4-chlorophenyl) disulfide, bis(4-bromophenyl) disulfide, bis(4-formylphenyl) disulfide, bis(4-nitrophenyl) disulfide, bis(4-trifluoromethylphenyl) disulfide.

[0023] Preferably, the oxidant is selected from: pyridinium chlorochromate (PCC), tert-butyl hydroperoxide (TBHP), di-tert-butyl peroxide (DTBP), tert-butyl peroxybenzoate (TBPB), meta-chloroperoxybenzoic acid (m-CPBA).

[0024] Preferably, the molecular sieve is selected from: 3Å molecular sieve, 4Å molecular sieve.

[0025] Preferably, the solvent is selected from one of ethanol, acetonitrile, acetone, dichloromethane, 1,2-dichloroethane, chloroform, toluene, chlorobenzene, trifluorotoluene, N,N-dimethylformamide, dimethyl sulfoxide, and tetrahydrofuran.

[0026] Preferably, the LED strip is selected from one of a blue LED strip, a green LED strip, and a white LED strip.

[0027] Preferably, the reaction time at room temperature is 24 hours.

[0028] Preferably, the dosage ratio of the molecular sieve to the substituted allene is (0.05 - 0.15) g∶0.5 mmol, such as 0.1 g∶0.5 mmol.

[0029] In the present invention, after the reaction is completed, the product is separated, purified, and processed by column chromatography.

[0030] The reaction process of the above technical solution can be expressed as: ; In the above structural formula, the selection of substituents refers to the above text.

[0031] Due to the application of the above technical solution, the present invention has the following advantages compared with the prior art: 1. The reaction conditions are mild, green, and easy to operate; 2. Through the reasonable design of the reaction substrate, the target product has a high yield and good selectivity; 3. The target product synthesized by the method has wide application value, which provides an effective method for synthesizing such compounds; 4. The 2(5H)-furanone derivative of the present invention has good inhibitory activity against the mycelial growth rate of phytopathogenic bacteria (such as Alternaria solani, Botrytis cinerea, and Gibberella zeae), has bactericidal activity, and can be used as a pesticide. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 It is the inhibition of Botrytis cinerea by the product of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0033] In the present invention, the substituted allene, the disubstituted aryl disulfide, the oxidant, and the molecular sieve are dissolved in a solvent, and the reaction is carried out at room temperature under the illumination of an LED strip to selectively obtain 3-(diarylphosphinyloxy)-4-arylthio-5-aryl-alkyl-2(5H)-furanone derivatives.

[0034] The present invention discloses a method for preparing a 2(5H)-furanone derivative. Without using metal-containing reagents, after the reaction is completed, the product can be effectively obtained as a 2(5H)-furanone derivative by performing conventional column chromatography separation and purification on the product.

[0035] The present invention will be further described below in conjunction with embodiments. The reagents used in the present invention are all existing products, and the specific preparation operations and performance tests are all conventional techniques. Unless otherwise specified, the reactions in the embodiments of the present invention are carried out in air at room temperature.

[0036] Example 1: 3-Diphenoxyphosphinyl-5-methyl-5-phenyl-4-phenylthio-2(5H)-furanone

[0037] Using (1-hydroxy-4-phenyl-4-methyl-2-diphenoxyphosphino)-2,3-allene and diphenyl disulfide as raw materials, the reaction steps are as follows: (1) Add (1-hydroxy-4,4-phenylmethyl-2-diphenoxyphosphino)-2,3-allene (0.5 mmol, 180 mg), diphenyl disulfide (0.25 mmol, 55 mg), PCC (0.5 mmol, 108 mg), 3 Å molecular sieve (0.1 g) and acetonitrile (5 mL) to the reaction flask, and react at room temperature for 24 hours under the illumination of a blue LED strip; (2) After the reaction is completed, the target product (yield 81%) is monitored by GC, and the obtained crude product is separated by column chromatography (dichloromethane:methanol = 95:5) to obtain the target product (195 mg). The analysis data of the product is as follows: 1 H NMR (400 MHz, CDCl3) δ 8.05 – 7.97 (m, 2H), 7.95 – 7.79 (m, 3H), 7.64 – 7.51 (m, 5H), 7.49 – 7.42 (m, 3H), 7.31 – 7.27 (m, 2H), 7.23 – 7.06 (m, 5H), 1.96 (s, 3H).

[0038] Expansion Example Referring to Example 1 and changing the conditions, the results in Table 1 are obtained.

[0039]

[0040] Table 1 Different Conditions and Results

[0041] Example 2: 3-Bis(2-chlorophenyl)oxyphosphinyl-5-methyl-5-phenyl-4-(4-methylphenylthio)-2(5H)-furanone

[0042] Using (1-hydroxy-4-phenyl-4-methyl-2-bis(2-chlorophenyl)phosphine oxide)-2,3-allenyl and bis(4-methylphenyl) disulfide as raw materials, the reaction steps are as follows: (1) Add (1-hydroxy-4-phenyl-4-methyl-2-bis(2-chlorophenyl)phosphine oxide)-2,3-allenyl (0.5 mmol, 215 mg), bis(4-methylphenyl) disulfide (0.25 mmol, 62 mg), TBHP (0.75 mmol, 68 mg), 4 Å molecular sieve (0.1 g) and acetonitrile (5 mL) to the reaction flask, and react at room temperature for 24 hours under the illumination of a blue LED strip; (2) After the reaction is completed, monitor by GC to obtain the target product (yield 78%). The crude product obtained is separated by column chromatography (dichloromethane:methanol = 95:5) to obtain the target product (219 mg). The analytical data of the product are as follows: 1 H NMR (400MHz, CDCl3) δ 8.05 – 7.97 (m, 2H), 7.95 – 7.79 (m, 3H), 7.64 – 7.51 (m, 5H),7.49 – 7.42 (m, 3H), 7.31 – 7.27 (m, 2H), 7.11 – 7.05 (m, 2H), 6.71 (d, J =3.0 Hz, 2H), 2.22 (s, 3H), 1.97 (s, 3H).

[0043] Example 3: 3-bis(3-chlorophenyl)phosphine oxide-5-methyl-5-(4-methoxyphenyl)-4-(4-methoxyphenylthio)-2(5H)-furanone

[0044] Using (1-hydroxy-4-(4-methoxyphenyl)-4-methyl-2-bis(3-chlorophenyl)phosphine oxide)-2,3-allenyl and bis(4-methoxyphenyl) disulfide as raw materials, the reaction steps are as follows: (1) Add (1-hydroxy-4-(4-methoxyphenyl)-4-methyl-2-bis(3-chlorophenyl)phosphine oxide)-2,3-allenyl (0.5 mmol, 230 mg), bis(4-methoxyphenyl) disulfide (0.75 mmol, 208 mg), DTBP (1 mmol, 146 mg), 4 Å molecular sieve (0.1 g) and acetonitrile (5 mL) to the reaction flask, and react at room temperature for 24 hours under the illumination of a white LED strip; (2)After the reaction, the crude product obtained by monitoring the target product (yield 80%) using GC was separated by column chromatography (dichloromethane:methanol = 95:5) to obtain the target product (245 mg). The analytical data of the product are as follows: 1 H NMR (400MHz, CDCl3) δ 7.57 – 7.51 (m, 2H), 7.45 – 7.42 (m, 2H), 7.31 – 7.29 (m, 4H),7.24 – 7.21 (m, 4H), 7.11 – 7.05 (m, 2H), 6.70 (d, J J = 3.0 Hz, 2H), 3.83 (s,3H), 3.81 (s, 3H), 1.97 (s, 3H).

[0045] Example 4: 3-Bis(4-chlorophenyl)phosphoryl-5-methyl-5-(4-chlorophenyl)-4-(4-fluorophenylthio)-2(5H)-furanone

[0046] Using (1-hydroxy-4-(4-chlorophenyl)-4-methyl-2-bis(4-chlorophenyl)phosphoryl)-2,3-allene and bis(4-fluorophenyl) disulfide as raw materials, the reaction steps are as follows: (1)Add (1-hydroxy-4-(4-chlorophenyl)-4-methyl-2-bis(4-chlorophenyl)phosphoryl)-2,3-allene (0.5 mmol, 232 mg), bis(4-fluorophenyl) disulfide (1 mmol, 254 mg), TBPB (1.25 mmol, 243 mg), 3Å molecular sieve (0.1 g) and dichloromethane (5 mL) to the reaction flask, and react at room temperature for 24 hours under white LED strip light illumination; (2)After the reaction, the crude product obtained by monitoring the target product (yield 85%) using GC was separated by column chromatography (dichloromethane:methanol = 95:5) to obtain the target product (256 mg). The analytical data of the product are as follows: 1 H NMR (400MHz, CDCl3) δ 7.72 – 7.67 (m, 4H), 7.40 (dd, J J = 8.3, 1.8 Hz, 2H), 7.36 (dd, J J = 8.3, 1.7 Hz, 2H), 7.31 (dd, J J = 5.6, 2.4 Hz, 2H), 7.23 (dt, J= 3.8, 2.1 Hz, 2H), 7.10 – 7.04 (m, 2H), 6.70 (d, J = 3.0 Hz, 2H), 1.97 (s, 3H).

[0047] Example 5: 3-Bis(4-fluorophenyl)phosphoryl-5-methyl-5-(4-ethoxycarbonylphenyl)-4-(4-bromophenylthio)-2(5H)-furanone

[0048] Using (1-hydroxy-4-(4-ethoxycarbonylphenyl)-4-methyl-2-bis(4-fluorophenyl)phosphoryl)-2,3-allene and bis(4-bromophenyl) disulfide as raw materials, the reaction steps are as follows: (1) Add (1-hydroxy-4-(4-ethoxycarbonylphenyl)-4-methyl-2-bis(4-fluorophenyl)phosphoryl)-2,3-allene (0.5 mmol, 234 mg), bis(4-bromophenyl) disulfide (0.5 mmol, 188 mg), m-CPBA (1.5 mmol, 259 mg), 3Å molecular sieve (0.1 g) and 1,2-dichloroethane (5 mL) into the reaction flask, and react at room temperature for 24 hours under the illumination of a white LED strip; (2) After the reaction is completed, monitor by GC to obtain the target product (yield 75%). The crude product obtained is separated by column chromatography (dichloromethane:methanol = 95:5) to obtain the target product (251 mg). The analytical data of the product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.72 – 7.65 (m, 4H), 7.41 (dd, J = 8.3, 1.8 Hz, 2H), 7.35 (dd, J = 8.3, 1.7 Hz, 2H), 7.30 (dd, J = 5.6, 2.4 Hz, 2H), 7.25 (dt, J = 3.8, 2.1 Hz, 2H), 7.11 – 7.05 (m, 2H), 6.71 (d, J = 3.0 Hz, 2H), 4.20 (m, 2H), 1.97 (s, 3H), 1.30 (t, J = 7.3 Hz, 3H).

[0049] Example VI: 3-Bis(4-bromophenyl)phosphoryl-5-methyl-5-(4-nitrophenyl)-4-(4-ethoxycarbonylphenylthio)-2(5H)-furanone

[0050] Using (1-hydroxy-4-(4-nitrophenyl)-4-methyl-2-bis(4-bromophenyl)phosphoryl)-2,3-allene and bis(4-ethoxycarbonylphenyl) disulfide as raw materials, the reaction steps are as follows: (1) Add (1-hydroxy-4-(4-nitrophenyl)-4-methyl-2-bis(4-bromophenyl)phosphoryl)-2,3-allene (0.5 mmol, 282 mg), bis(4-ethoxycarbonylphenyl) disulfide (0.5 mmol, 181 mg), TBHP (1 mmol, 90 mg), 4Å molecular sieve (0.1 g) and chloroform (5 mL) to the reaction flask, and react at room temperature for 24 hours under white LED strip light irradiation; After the reaction, monitor by GC to obtain the target product (yield 71%). The crude product obtained is separated by column chromatography (dichloromethane:methanol = 95:5) to obtain the target product (269 mg). The analysis data of the product are as follows: 1 H NMR (400MHz, CDCl3) δ 7.72 – 7.65 (m, 4H), 7.42 (dd, J = 8.3, 1.8 Hz, 2H), 7.37 (dd, J = 8.3, 1.6 Hz, 2H), 7.31 (dd, J = 5.6, 2.2 Hz, 2H), 7.24 (dt, J = 3.8, 2.1Hz, 2H), 7.10 – 7.04 (m, 2H), 6.70 (d, J = 3.0 Hz, 2H), 4.30 (m, 2H), 1.97(s, 3H), 1.30 (t, J = 7.3 Hz,3H).

[0051] Example VII: 3-Bis(4-methylphenyl)phosphoryl-5-methyl-5-phenyl)-4-(4-nitrophenylthio)-2(5H)-furanone

[0052] Using (1-hydroxy-4-phenyl-4-methyl-2-bis(4-chlorophenyl)phosphoryl)-2,3-allene and bis(4-nitrophenyl) disulfide as raw materials, the reaction steps are as follows: (1) Add (1-hydroxy-4-phenyl-4-methyl-2-bis(4-chlorophenyl)phosphoryl)-2,3-allene (0.5 mmol, 194 mg), bis(4-nitrophenyl) disulfide (0.75 mmol, 231 mg), TBHP (1 mmol, 90 mg), 4 Å molecular sieve (0.1 g) and toluene (5 mL) into a reaction flask, and react at room temperature for 24 hours under the illumination of a blue LED strip; (2) After the reaction, monitor the reaction by GC to obtain the target product (yield 87%). The crude product obtained is separated by column chromatography (dichloromethane:methanol = 95:5) to obtain the target product (241 mg). The analytical data of the product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.80 – 7.73 (m, 4H), 7.45 – 7.40 (m, 4H), 7.35 (m, 2H), 7.29(m, 2H) 7.23 – 7.06 (m, 5H), 1.96 (s, 3H), 1.33 (s, 3H), 1.27 (s, 3H).

[0053] Example 8: 3-bis(4-methoxyphenyl)phosphoryl-5-methyl-5-phenyl-4-(4-trifluoromethylphenylthio)-2(5H)-furanone

[0054] Using (1-hydroxy-4-phenyl-4-methyl-2-bis(4-methoxyphenyl)phosphoryl)-2,3-allene and bis(4-trifluoromethylphenyl) disulfide as raw materials, the reaction steps are as follows: (1) Add (1-hydroxy-4-phenyl-4-methyl-2-bis(4-methoxyphenyl)phosphoryl)-2,3-allene (0.5 mmol, 218 mg), bis(4-trifluoromethylphenyl) disulfide (0.75 mmol, 265 mg), DTBP (1 mmol, 146 mg), 4 Å molecular sieve (0.1 g) and chlorobenzene (5 mL) into a reaction flask, and react at room temperature for 24 hours under the illumination of a white LED strip; (2) After the reaction, monitor the reaction by GC to obtain the target product (yield 83%). The crude product obtained is separated by column chromatography (dichloromethane:methanol = 95:5) to obtain the target product (253 mg). The analytical data of the product are as follows: 11H NMR (400 MHz, CDCl3) δ 7.81 – 7.75 (m, 4H), 7.43 – 7.38 (m, 4H), 7.34 (m, 2H), 7.29 (m, 2H), 7.23 – 7.06 (m, 5H), 3.83 (s, 3H), 3.81 (s, 3H), 1.98 (s, 3H).

[0055] Example 9: 3-Bis(4-trifluoromethoxyphenyl)phosphoryl-5-methyl-5-phenyl-4-phenylthio-2(5H)-furanone

[0056] Using (1-hydroxy-4-phenyl-4-methyl-2-bis(4-trifluoromethoxyphenyl)phosphoryl)-2,3-allene and diphenyl disulfide as raw materials, the reaction steps are as follows: (1) Add (1-hydroxy-4-phenyl-4-methyl-2-bis(4-trifluoromethoxyphenyl)phosphoryl)-2,3-allene (0.5 mmol, 264 mg), diphenyl disulfide (0.5 mmol, 109 mg), DTBP (1 mmol, 146 mg), 3 Å molecular sieve (0.1 g) and trifluorotoluene (5 mL) to the reaction flask, and react at room temperature for 24 hours under the illumination of a blue LED strip light; (2) After the reaction is completed, monitor by GC to obtain the target product (yield 77%). The crude product obtained is separated by column chromatography (methylene chloride:methanol = 95:5) to obtain the target product (250 mg). The analysis data of the product are as follows: 1 1H NMR (400 MHz, CDCl3) δ 7.81 – 7.75 (m, 4H), 7.49 – 7.38 (m, 7H), 7.31 – 7.27 (m, 2H), 7.23 – 7.06 (m, 5H), 1.96 (s, 3H).

[0057] Example 10: 3-Bis(4-nitrophenyl)phosphoryl-5-methyl-5-phenyl-4-phenylthio-2(5H)-furanone

[0058] Using (1-hydroxy-4-phenyl-4-methyl-2-bis(4-nitrophenyl)phosphoryl)-2,3-allene and diphenyl disulfide as raw materials, the reaction steps are as follows: Add (1-hydroxy-4-phenyl-4-methyl-2-bis(4-nitrophenyl)phosphoryl)-2,3-allene (0.5 mmol, 225 mg), diphenyldisulfide (1 mmol, 218 mg), m-CPBA (1 mmol, 172 mg), 3 Å molecular sieve (0.1 g) and acetonitrile (5 mL) into a reaction flask, and react at room temperature for 24 hours under the illumination of a white LED strip; After the reaction, the crude product obtained by monitoring the target product (yield 65%) by GC was separated by column chromatography (dichloromethane:methanol = 95:5) to obtain the target product (186 mg). The analytical data of the product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.80 – 7.75 (m, 4H), 7.49 – 7.35 (m, 7H), 7.31 – 7.28 (m, 2H), 7.21 – 7.04 (m, 5H), 1.96 (s, 3H).

[0059] Example XI: 3-diphenyphosphoryl-5-ethyl-5-phenyl-4-phenylthio-2(5H)-furanone

[0060] Using (1-hydroxy-4-phenyl-4-ethyl-2-diphenyphosphoryl)-2,3-allene and diphenyldisulfide as raw materials, the reaction steps are as follows: (1) Add (1-hydroxy-4-phenyl-4-ethyl-2-diphenyphosphoryl)-2,3-allene (0.5 mmol, 187 mg), diphenyldisulfide (0.5 mmol, 109 mg), PCC (0.75 mmol, 162 mg), 4 Å molecular sieve (0.1 g) and dimethyl sulfoxide (5 mL) into a reaction flask, and react at room temperature for 24 hours under the illumination of a white LED strip; After the reaction, the crude product obtained by monitoring the target product (yield 84%) by GC was separated by column chromatography (dichloromethane:methanol = 95:5) to obtain the target product (208 mg). The analytical data of the product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.84 – 7.72 (m, 4H), 7.59 – 7.54 (m, 2H), 7.51 – 7.35 (m, 7H), 7.31 – 7.29 (m, 2H), 7.23 – 7.07 (m, 5H), 1.97 (dd, J = 14.3, 7.0 Hz, 2H), 0.96 (t,J = 7.2 Hz, 3H).

[0061] Example XII: 3-Diphenylphosphinyl-5-propyl-5-phenyl-4-phenylthio-2(5H)-furanone

[0062] Using (1-hydroxy-4-phenyl-4-propyl-2-diphenylphosphinyl)-2,3-allene and diphenyldisulfide as raw materials, the reaction steps are as follows: (1) Add (1-hydroxy-4-phenyl-4-propyl-2-diphenylphosphinyl)-2,3-allene (0.5 mmol, 194 mg), diphenyldisulfide (0.75 mmol, 163 mg), TBHP (0.75 mmol, 68 mg), 4Å molecular sieve (0.1 g) and tetrahydrofuran (5 mL) to the reaction flask, and react at room temperature for 24 hours under the illumination of a blue LED strip; (2) After the reaction is completed, monitor the target product by GC (yield 82%). The obtained crude product is separated by column chromatography (dichloromethane:methanol = 95:5) to obtain the target product (209 mg). The analysis data of the product are as follows: 1 H NMR (400MHz, CDCl3) δ 7.84 – 7.72 (m, 4H), 7.59 – 7.54 (m, 2H), 7.51 – 7.42 (m, 7H),7.31 – 7.27 (m, 2H), 7.23 – 7.06 (m, 5H), 1.87 (t, J = 7.0 Hz, 2H), 1.30 (m,2H), 0.90 (t, J = 7.2 Hz, 3H).

[0063] Example XIII: Determination of Bactericidal Activity Study and determine the inhibitory activities of the 3 synthesized compounds on the mycelial growth rates of 3 plant-derived pathogens, Alternaria solani, Botrytis cinerea, and Fusarium graminearum, to evaluate the bactericidal activities of the target compounds.

[0064] The mycelial growth rate method was used to determine the biological activity, which is a conventional technique and is briefly described as follows: First, three test pathogens were activated and subcultured twice on PDA medium. When the mycelia had almost covered the medium, the mycelia at the outermost periphery of the activated fungal cakes were punched out with a punch to obtain 5-mm-diameter fungal cakes for standby. The above-mentioned fungal cakes were transferred onto the prepared culture dishes containing the drug and cultured at 25 °C. When the mycelial diameter of the colonies in the blank group reached 6.5 - 7.0 cm, they could be taken out for measurement. A drug-free culture dish was set as the control (CK), the solvent amounts in the treatment group and the blank group were equivalent, and osthole was used as the control agent. Each group had 3 parallels.

[0065] Data processing: Inhibition rate (%) = (C K − treatment group) / (C K − 5) × 100% Figure 1 This is the inhibition of the product of the present invention against Botrytis cinerea of strawberries. The following table shows the calculated inhibition rates, and it can be seen that the product of the present invention has excellent antibacterial properties.

[0066]

[0067] Inhibition rate of the compound against the test fungus (50 μg / mL) a

[0068] a The average value of three parallel data; b The commercial agent osthole was used as the control agent; c A positive value indicates inhibition of the growth of the pathogen, a negative value indicates promotion of the growth of the pathogen, and 0 indicates no effect.

[0069] The 2(5H)-furanone derivative of the present invention has good inhibitory activity on the mycelial growth rate of plant-derived pathogens (such as Alternaria solani, Botrytis cinerea, and Gibberella zeae), has bactericidal activity, and can be used as a pesticide.

Claims

1. A method for preparing a 2(5H)-furanone derivative, characterized in that, It includes the following steps: using substituted allene and disubstituted aryl disulfide as raw materials to react and prepare 2(5H)-furanone derivatives; The substituted allene is shown as the following general chemical structure formula: ； wherein R 1 , R 2 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, halogen, haloalkoxy, and nitro; n is from 0 to 10; The disubstituted aryl disulfide is shown as the following general chemical structure formula: ； Among them, R 3 is selected from one of hydrogen, alkyl, alkoxy, halogen, ester group, nitro, and haloalkyl.

2. The preparation method of the 2(5H)-furanone derivative according to claim 1, wherein, Using substituted allene and disubstituted aryl disulfide as raw materials, reacting in the presence of an oxidant, molecular sieve and solvent to prepare 2(5H)-furanone derivatives.

3. The preparation method of the 2(5H)-furanone derivative according to claim 2, characterized in that, The molar ratio of the substituted allene, disubstituted aryl disulfide and oxidant is 1∶(0.5 - 2)∶(1 - 3).

4. The preparation method of the 2(5H)-furanone derivative according to claim 3, characterized in that, The oxidant is selected from one or more of pyridinium chlorochromate, tert-butyl hydroperoxide, di-tert-butyl peroxide, tert-butyl peroxybenzoate, and m-chloroperoxybenzoic acid.

5. The preparation method of the 2(5H)-furanone derivative according to claim 1, characterized in that, The reaction is carried out under light, and the reaction temperature is 10 - 50 °C for 5 - 50 hours. 2(5H)-furanone derivatives prepared by the preparation method of the 2(5H)-furanone derivatives described in any one of claims 1 to 5.

7. A method for plant sterilization, characterized in that, It includes the following steps: applying a reagent containing the 2(5H)-furanone derivative described in claim 6 to plants to achieve plant sterilization.

8. A drug, characterized in that, The active ingredient of the drug includes the 2(5H)-furanone derivative described in claim 6.

9. Use of the 2(5H)-furanone derivative described in claim 6 as a biocide or in the preparation of a biocide.

10. The application according to claim 9, characterized in that, The biocide includes pesticides.

Images