5-hydroxy-3-alkylthio-2-cyclopentenone derivative and preparation method thereof

Abstract

The invention relates to a 5-hydroxy-3-alkylthio-2-cyclopentenone derivative and a preparation method of the 5-hydroxy-3-alkylthio-2-cyclopentenone derivative. The chemical general formula of the derivative is shown in the specification. The preparation method comprises the following steps: adding an alpha-enoyl ketene dithioacetal compound, Selectfluor, water and a solvent into a closed reactor, and reacting for 2-24 hours at the temperature of 60-120 DEG C in a nitrogen atmosphere, so as to obtain the 5-hydroxy-3-alkylthio-2-cyclopentenone derivative. The method has the advantages of few synthesis steps, cheap and easily available raw materials, mild reaction conditions, simplicity in operation, no metal residue and easiness in industrialization. # imgabs0 #

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical chemical intermediates and organic synthetic chemistry, and relates to a 5-hydroxy-3-alkylthio-2-cyclopentenone derivative and a preparation method thereof. Background Art

[0002] 2-Cyclopentenone and its derivatives are highly respected in the field of organic synthesis and are extremely important synthetic intermediates, showing excellent practicality. In addition, these compounds are also popular structural units in many drugs and natural products, such as pyrethrins, ketedonolone, prostaglandins, sesquiterpenes, Przewalski B, tepsilocin, acharenolone, acetyl dimer B, etc. (Tetrahedron, 2024, 150, 133747), further highlighting their importance. Therefore, the development and development of effective methods to prepare these important compounds has received considerable attention.

[0003] At present, the two most important and applicable methods for synthesizing cyclopentenone are Nazarov cyclization reaction and Pauson-Khand reaction. In 1971, Pauson and Khand et al. found that one molecule of alkene, one molecule of alkyne and one molecule of CO under the catalysis of cobalt undergo [2+2+1] cycloaddition, thus realizing the synthesis of cyclopentenone (Chem Soc Rev, 2004, 33, 32-42); in 2005, Alison J. Frontiera and Christina Collison summarized the research on Nazarov cyclization reaction, indicating that this reaction has become a key step in the synthesis of several natural products, and proved the application of Nazarov cyclization in the synthesis of complex molecules (Tetrahedron, 2005, 61, 7577–7606); in 2013, Wang Mang's research group reported the intramolecular reduction Heck reaction of α-enoyl dithioacetal under the catalysis of precious metal palladium, and established a synthetic method for 3-alkylthio-2-cyclopentenone derivatives (Chem. Commun., 2013, 49, 2201). However, these approaches still have some shortcomings, such as the use of toxic CO, limited substrates, harsh reaction conditions, and the use of precious metals as catalysts. Patent "A method for preparing cyclopentenone derivatives" (application number: 202310283788.0), the method includes the following steps: adding the substrate a-enoyl dithioacetal and triphenylphosphine, cuprous bromide, potassium bromodifluoroacetate to the reaction vessel, using dioxane as the reaction solvent, reacting for 10-12 hours at 100-130°C in a nitrogen atmosphere, and finally obtaining cyclopentenone derivatives through extraction, drying, and silica gel column chromatography after the reaction. However, since the catalyst is cuprous bromide, the post-processing process is complicated and may cause metal residue problems.

[0004] Therefore, in order to meet the growing needs of science and practical applications, exploring simple, green and effective methods for synthesizing structurally diverse 2-cyclopentenone compounds has important theoretical research value and practical application significance. Summary of the invention

[0005] The purpose of the present invention is to provide a 5-hydroxy-3-alkylthio-2-cyclopentenone derivative and a preparation method thereof in view of the limitations of the current technology. The derivative has a hydroxyl group at the 5-position of cyclopentenone, so that the functional group can be further transformed and modified, and has rich substrate expansibility; in the preparation, no precious metal or transition metal is used as a catalyst, which can reduce the problem of metal residues in the subsequent drug synthesis using the 5-hydroxycyclopentenone skeleton. The present invention has few synthesis steps, cheap and readily available raw materials, mild reaction conditions, simple operation, no metal residue, and is easy to industrialize.

[0006] The technical solution of the present invention is:

[0007] A 5-hydroxy-3-alkylthio-2-cyclopentenone derivative, the general chemical formula of the derivative is as follows:

[0008]

[0009] Where:

[0010] R 1is a hydrogen atom; various C1-C12 hydrocarbon groups; fluorine, chlorine, bromine, iodine; nitro; cyano; benzyl substituted with fluorine, chlorine, bromine, iodine, nitro, cyano, carboxyl, sulfonic acid, aldehyde, C1-C8 hydrocarbon group, C1-C6 hydrocarbon acyl group, C1-C6 hydrocarbon alkoxycarbonyl group, C1-C6 hydrocarbon amide; (hetero) aromatic rings with fluorine, chlorine, bromine, iodine, nitro, cyano, carboxyl, sulfonic acid, (hetero)aryl substituted with aldehyde, C1-C8 hydrocarbon, C1-C6 hydrocarbon acyl, C1-C6 hydrocarbon alkoxycarbonyl, C1-C6 hydrocarbon amide; (hetero)aryl substituted with fluorine, chlorine, bromine, iodine, nitro, cyano, carboxyl, sulfonic acid, aldehyde, C1-C8 hydrocarbon, C1-C6 hydrocarbon acyl, C1-C6 hydrocarbon alkoxycarbonyl, C1-C6 hydrocarbon amide on the (hetero)aromatic ring Acyl; acyl of C0-C8 hydrocarbon; carboxyl; ester carbonyl substituted by C1-C12 hydrocarbon or (hetero)aryl; amide carbonyl substituted by C1-C12 hydrocarbon or (hetero)aryl; vinyl substituted by fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C4 hydrocarbon, (hetero)aryl, C1-C8 hydrocarbon alkoxycarbonyl, C1-C8 hydrocarbon and (hetero)aryl amide, sulfonic acid group on double bond; Ethylene groups substituted with fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C4 hydrocarbon, (hetero)aryl, C1-C8 hydrocarbon alkoxycarbonyl, C1-C8 hydrocarbon and (hetero)arylamide, or sulfonic acid; allyl groups substituted with fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C4 hydrocarbon, (hetero)aryl, C1-C8 hydrocarbon alkoxycarbonyl, C1-C8 hydrocarbon and (hetero)arylamide, or sulfonic acid on the double bond;

[0011] R 2 The benzyl ring is connected with fluorine, chlorine, bromine, iodine, nitro, cyano, carboxyl, sulfonic acid, aldehyde, C1-C8 hydrocarbon, C1-C6 hydrocarbon acyl, C1-C6 hydrocarbon alkoxycarbonyl, C1-C6 hydrocarbon amide substituted benzyl; the double bond is connected with fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C4 hydrocarbon, (hetero)aryl, C1-C8 hydrocarbon alkoxycarbonyl, C1-C8 hydrocarbon Allyl substituted with nitro, cyano, sulfonic acid, carboxyl, C1-C8 hydrocarbon alkoxycarbonyl, C1-C8 alkyl and (hetero)aryl amide, and sulfonic acid; methylene substituted with nitro, cyano, sulfonic acid, carboxyl, C1-C8 hydrocarbon alkoxycarbonyl, C1-C8 alkyl and (hetero)aryl amide; propargyl substituted with fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C4 hydrocarbon, (hetero)aryl, C1-C8 hydrocarbon alkoxycarbonyl, C1-C8 hydrocarbon and (hetero)aryl amide, and sulfonic acid;

[0012] R 3It is hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, cyclohexyl, benzyl, phenyl, aryl with substituents on the benzene ring, and heteroaryl with substituents. The substituents on the (hetero)aryl are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, cyclohexyl, aryl, alkoxy, alkylthio, C1-C6 alkoxy ester, C1-C6 alkyl substituted amide, aldehyde, cyano, nitro, fluorine, chlorine, bromine, iodine, allyl, sulfonic acid, carboxyl, benzyl. The heteroaryl is pyridine, furan, thiophene, thiazole, oxazole, pyridazine, etc. The number of substituents on the (hetero)aryl is 1-5.

[0013] The preparation method of the 5-hydroxy-3-alkylthio-2-cyclopentenone derivative comprises the following steps:

[0014] Add α-enoyl dithioacetal compound, Selectfluor, water and solvent into a reactor, seal it and react it at 60-120° C. for 2-24 hours in a nitrogen atmosphere to obtain a 5-hydroxy-3-alkylthio-2-cyclopentenone derivative;

[0015] Among them, α-enoyl disulfide ketal compounds: Selectfluor: H 2 The molar dosage of O is 1:0.8-2.0:0.1-3.0;

[0016] The α-enoyl disulfide ketene compound is represented by the following general formula:

[0017]

[0018] Among them, R 1is a hydrogen atom; various C1-C12 hydrocarbon groups; fluorine, chlorine, bromine, iodine; nitro; cyano; benzyl substituted with fluorine, chlorine, bromine, iodine, nitro, cyano, carboxyl, sulfonic acid, aldehyde, C1-C8 hydrocarbon group, C1-C6 hydrocarbon acyl group, C1-C6 hydrocarbon alkoxycarbonyl group, C1-C6 hydrocarbon amide; (hetero) aromatic rings with fluorine, chlorine, bromine, iodine, nitro, cyano, carboxyl, sulfonic acid, (hetero)aryl substituted with aldehyde, C1-C8 hydrocarbon, C1-C6 hydrocarbon acyl, C1-C6 hydrocarbon alkoxycarbonyl, C1-C6 hydrocarbon amide; (hetero)aryl substituted with fluorine, chlorine, bromine, iodine, nitro, cyano, carboxyl, sulfonic acid, aldehyde, C1-C8 hydrocarbon, C1-C6 hydrocarbon acyl, C1-C6 hydrocarbon alkoxycarbonyl, C1-C6 hydrocarbon amide on the (hetero)aromatic ring Acyl; acyl of C0-C8 hydrocarbon; carboxyl; ester carbonyl substituted by C1-C12 hydrocarbon or (hetero)aryl; amide carbonyl substituted by C1-C12 hydrocarbon or (hetero)aryl; vinyl substituted by fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C4 hydrocarbon, (hetero)aryl, C1-C8 hydrocarbon alkoxycarbonyl, C1-C8 hydrocarbon and (hetero)aryl amide, sulfonic acid group on double bond; Ethylene groups substituted with fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C4 hydrocarbon, (hetero)aryl, C1-C8 hydrocarbon alkoxycarbonyl, C1-C8 hydrocarbon and (hetero)arylamide, or sulfonic acid; allyl groups substituted with fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C4 hydrocarbon, (hetero)aryl, C1-C8 hydrocarbon alkoxycarbonyl, C1-C8 hydrocarbon and (hetero)arylamide, or sulfonic acid on the double bond;

[0019] R 2 The benzyl ring is connected with fluorine, chlorine, bromine, iodine, nitro, cyano, carboxyl, sulfonic acid, aldehyde, C1-C8 hydrocarbon, C1-C6 hydrocarbon acyl, C1-C6 hydrocarbon alkoxycarbonyl, C1-C6 hydrocarbon amide substituted benzyl; the double bond is connected with fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C4 hydrocarbon, (hetero)aryl, C1-C8 hydrocarbon alkoxycarbonyl, C1-C8 hydrocarbon Allyl substituted with nitro, cyano, sulfonic acid, carboxyl, C1-C8 hydrocarbon alkoxycarbonyl, C1-C8 alkyl and (hetero)aryl amide, and sulfonic acid; methylene substituted with nitro, cyano, sulfonic acid, carboxyl, C1-C8 hydrocarbon alkoxycarbonyl, C1-C8 alkyl and (hetero)aryl amide; propargyl substituted with fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C4 hydrocarbon, (hetero)aryl, C1-C8 hydrocarbon alkoxycarbonyl, C1-C8 hydrocarbon and (hetero)aryl amide, and sulfonic acid;

[0020] R 3It is hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, cyclohexyl, benzyl, phenyl, aryl with substituents on the benzene ring, and heteroaryl with substituents. The substituents on the (hetero)aryl are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, cyclohexyl, aryl, alkoxy, alkylthio, C1-C6 alkoxy ester, C1-C6 alkyl substituted amide, aldehyde, cyano, nitro, fluorine, chlorine, bromine, iodine, allyl, sulfonic acid, carboxyl, benzyl. The heteroaryl is pyridine, furan, thiophene, thiazole, oxazole, pyridazine, etc. The number of substituents on the (hetero)aryl is 1-5.

[0021] The solvent is: toluene, xylene, sulfolane, N,N-dimethylformamide, N,N-dimethylacetamide, anisole, chlorobenzene, dimethyl sulfoxide, 1,3-dimethyl-2-imidazolidinone, 1,4-dioxane, acetonitrile, butyronitrile, N-methylpyrrolidone, methyl tert-butyl ether, cyclohexanone, tetrahydrofuran, dichloroethane or dichloromethane;

[0022] 0.2-1.0 mmol of α-enoyl disulfide ketene compound is added for every 2-5 ml of solvent.

[0023] The method further comprises the following steps: pouring the obtained reaction solution into saturated saline to quench, then extracting with an extractant, drying the obtained organic phase with a desiccant, distilling and recovering the solvent, and separating and purifying the residue by silica gel column chromatography to complete the purification;

[0024] The extractant is one or more of ethyl acetate, dichloromethane, n-hexane, cyclohexane, acetone, ethyl ether, n-butyl ether, cyclohexanone, ethyl propionate, butyl acetate, etc., and its volume is 2 to 4 times that of the reaction solvent; the desiccant is one or more of anhydrous magnesium sulfate, anhydrous sodium sulfate, calcium chloride, magnesium chloride, sodium carbonate, calcium hydroxide, etc.;

[0025] In the separation and purification of the product, the eluent used for column chromatography is one or more of petroleum ether, n-hexane, cyclohexane, acetone, acetonitrile, methanol, ethanol, acetic acid, ethyl acetate, toluene, benzene, triethylamine, dichloromethane, chloroform, etc.

[0026] In N 2Under a certain atmosphere, add the above-mentioned α-enoyl disulfide acetal (1 mmol), Selectfluor (0.8-2 mmol) and water (0.1-3 mmol) raw materials to a certain organic solvent (2-5 mL) as mentioned above (the above amount can be scaled up proportionally). After the addition is completed, stir at a specific temperature and monitor the reaction by thin layer chromatography; after post-treatment, separate and obtain 5-hydroxy-3-alkylthio-2-cyclopentenone compound. The yield is between 22% and 97% depending on different reactions, see the specific implementation examples for details.

[0027] The beneficial effects of the present invention are:

[0028] The invention provides a simple and efficient new method for preparing novel 2-cyclopentenone compounds. The synthesized 5-hydroxy-3-alkylthio-2-cyclopentenone derivatives have abundant functional groups that can be further modified, provide a simple and universal method for synthesizing a library of novel 2-cyclopentenone compounds with potential biological activity, can be used as drug intermediates in pesticides, medicines, photophysical materials and genetics, and especially occupy an important position in the field of drug synthesis. The method has few synthesis steps, cheap and readily available raw materials, mild reaction conditions, simple operation, no metal residue, easy process and industrialization, and has good application prospects, promotion value and actual production potential. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 is the hydrogen nuclear magnetic resonance spectrum obtained in Example 1;

[0030] Figure 2 is the carbon NMR spectrum obtained in Example 1;

[0031] Figure 3 is the hydrogen nuclear magnetic resonance spectrum obtained in Example 2;

[0032] Figure 4 is the carbon NMR spectrum obtained in Example 2;

[0033] Figure 5 is the hydrogen nuclear magnetic resonance spectrum obtained in Example 3;

[0034] Figure 6 is the carbon NMR spectrum obtained in Example 3; DETAILED DESCRIPTION

[0035] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0036] The chemical formula of the starting material α-enoyl ketene disulfide acetal used in the present invention is:

[0037] This substance is a known substance. The preparation method is as follows:

[0038]

[0039] The chemical reaction formula is as follows:

[0040]

[0041] The Selectfluor of the present invention is a well-known substance, and its Chinese name is 1-chloromethyl-4-fluoro-1,4-diazidebicyclo[2.2.2]octane bistetrafluoroborate.

[0042] Embodiment 1:

[0043] Preparation of 2-cyclopentenone compound 2a

[0044]

[0045] (E)-1,1-bis(ethylthio)-2-(4-chlorophenyl)-5-phenylpenta-1,4-dien-3-one 1a (194 mg, 0.5 mmol) (starting material), Selectfluor (779 mg, 0.55 mmol) (C-S bond activating reagent), H 2 O (13.5 mg, 0.75 mmol) (hydroxyl source) was mixed and added into a reaction kettle containing 4 ml of the reaction solvent acetonitrile. After sealing, the reaction was reacted at 90°C under nitrogen for 10 h. The obtained reaction solution was then poured into saturated brine to quench. The obtained reaction solution was then extracted with ethyl acetate as an extractant. The obtained organic phase was dried over anhydrous magnesium sulfate. After the solvent was distilled back, it was chromatographed on a silica gel column to obtain a yellow solid 2-(4-chlorophenyl)-3-(ethylthio)-4-phenyl-5-hydroxycyclopent-2-ene-1-one 2a (160.36 mg, yield was 93%).

[0046] (Among them, R 1 is 4-chlorophenyl, R 2 Ethyl, R 3 is phenyl;)

[0047] Data analysis:

[0048] like Figure 1 and Figure 2 As shown, Light yellow solid.mp 131-132℃. 1 H NMR (400 MHz, CDCl 3)δ1.11(t,J=7.2Hz,3H),2.54-2.68(m,1H),2.85-2.94(m,1H),4.62(s,2H),7.15 (d,J=7.2Hz,2H),7.30-7.53(m,3H),7.41(d,J=8.0Hz,2H),7.58(d,J=8.0Hz,2H). 13 C NMR (100 MHz, CDCl 3 )δ13.9,25.0,52.7,75.2,128.0,128.4(2C),128.5(2C),129.0(2C),129 .1,130.0(2C),132.6,133.9,135.6,171.1,201.3.HRMS(ESI)m / z:[M+Na] + Calculate for C 19 H 17 ClNaO 2 S + 367.0530, found 367.0527.

[0049] Embodiment 2:

[0050] Preparation of 2-cyclopentenone compound 2b

[0051]

[0052] Under nitrogen conditions, (E)-1,1-bis(ethylthio)-2-(3,4-dimethoxyphenyl)-5-phenylpenta-1,4-dien-3-one 1b (207.3 mg, 0.5 mmol), Selectfluor (779 mg, 0.55 mmol), H 2 O (13.5 mg, 0.75 mmol) was mixed and added into a reaction kettle containing 4 ml of the reaction solvent acetonitrile. After sealing, the reaction was reacted at 90 ° C under nitrogen for 10 h, and then the obtained reaction solution was poured into saturated brine to quench. Then, ethyl acetate was used as an extractant for extraction, and the obtained organic phase was dried over anhydrous magnesium sulfate. After distillation to recover the solvent, it was chromatographed on a silica gel column to obtain a yellow solid 2-(3,4-dimethoxyphenyl)-3-(ethylthio)-4-phenyl-5-hydroxycyclopent-2-ene-1-one 2b (150 mg, yield was 81%).

[0053] (Among them, R 1 is 3,4-dimethoxyphenyl, R 2 Ethyl, R 3 is phenyl;)

[0054] Data analysis:

[0055] As Figure 3 and Figure 4 shown, Light yellow solid. mp 121 - 122 °C. 1 H NMR (400 MHz, CDCl 3 ) δ 1.13 (t, J = 7.6 Hz, 3H), 2.56 - 2.65 (m, 1H), 2.87 - 2.96 (m, 1H), 3.91 (s, 6H), 4.63 (s, 2H), 6.95 (d, J = 8.4 Hz, 1H), 7.18 (d, J = 7.2 Hz, 2H), 7.24 (d, J = 13.2 Hz, 3H), 7.32 - 7.38 (m, 3H). 13 C NMR (100 MHz, CDCl 3 ) δ 14.0, 25.0, 52.7, 55.8, 55.9, 75.3, 110.8, 111.8, 121.7, 123.2, 128.0, 128.5 (2C), 129.0 (2C), 133.5, 135.9, 148.6, 148.9, 169.1, 201.7. HRMS (ESI) m / z: [M + Na] + calcd for C 21 H 22 NaO 4 S + 393.1131, found 393.1135.

[0056] Example 3:

[0057] Preparation of 2 - cyclopentenone compound 2c

[0058]

[0059] Under nitrogen, (E)-1,1 - bis(ethylthio)-2-(4 - chlorophenyl)-5 - p - tolylpenta - 1,4 - dien - 3 - one 1c (201.5 mg, 0.5 mmol), Selectfluor (779 mg, 0.55 mmol), H 2 O (13.5 mg, 0.75 mmol) were mixed and added to a reaction kettle containing 4 ml of the reaction solvent acetonitrile. After sealing, the reaction was carried out at 90 °C for 10 h under nitrogen. Then, the obtained reaction solution was poured into saturated brine for quenching, and then extracted with ethyl acetate as the extractant. The obtained organic phase was dried with anhydrous magnesium sulfate. After distilling and recovering the solvent, silica gel column chromatography was used to obtain the yellow solid 2-(4 - chlorophenyl)-3-(ethylthio)-4 - p - tolyl - 5 - hydroxycyclopent - 2 - en - 1 - one 2a (152.5 mg, yield 85%).

[0060] (Among them, R 1 is 4-chlorophenyl, R 2 Ethyl, R 3 is p-tolyl;)

[0061] Data analysis:

[0062] like Figure 5 and Figure 6 As shown, Light yellow solid.mp 117-118℃. 1 H NMR (400 MHz, CDCl 3 )δ1.14(t,J=7.2Hz,3H),2.34(s,3H),2.60-2.65(m,1H),2.88-2.95(m,1H),4.61(s,2H), 7.05(d,J=7.2Hz,2H),7.17(d,J=8.0Hz,2H),7.42(d,J=8.0Hz,2H),7.59(d,J=7.6Hz,2H). 13 C NMR (100 MHz, CDCl 3 )δ13.9,21.0,25.0,56.2,75.2,128.3(2C),128.5(2C),129.1,129.8(2C),130.1(2C),132.4,133.9,137.9,171.3,201.3.HRMS(ESI)m / z:[M+Na] + calcdfor C 20 H 19 ClNaO 2 S + 381.0686, found 381.0688.

[0063] Example 4

[0064]

[0065] The other steps are the same as in Example 1, except that R 1 Replace 4-chlorophenyl with iodine, R 2 Replace ethyl with methyl, R 3 Phenyl is replaced by p-methoxyphenyl;

[0066] Example 5

[0067]

[0068] The other steps are the same as in Example 1, except that R 3 Replacement of phenyl with benzo[1,3]dioxolane;

[0069] Example 6

[0070]

[0071] The other steps are the same as in Example 1, except that R 3 Replace the phenyl group with furan.

[0072] Matters not covered by the present invention are known technologies.

Claims

1. A 5-hydroxy-3-alkylthio-2-cyclopentenone derivative, characterized in that: The chemical formula of the derivative is as follows: Where: R 1 is a hydrogen atom; various C1-C12 hydrocarbon groups; fluorine, chlorine, bromine, iodine; nitro; cyano; benzyl substituted with fluorine, chlorine, bromine, iodine, nitro, cyano, carboxyl, sulfonic acid, aldehyde, C1-C8 hydrocarbon group, C1-C6 hydrocarbon acyl group, C1-C6 hydrocarbon alkoxycarbonyl group, C1-C6 hydrocarbon amide; (hetero) aromatic rings with fluorine, chlorine, bromine, iodine, nitro, cyano, carboxyl, sulfonic acid, (hetero)aryl substituted with aldehyde, C1-C8 hydrocarbon, C1-C6 hydrocarbon acyl, C1-C6 hydrocarbon alkoxycarbonyl, C1-C6 hydrocarbon amide; (hetero)aryl substituted with fluorine, chlorine, bromine, iodine, nitro, cyano, carboxyl, sulfonic acid, aldehyde, C1-C8 hydrocarbon, C1-C6 hydrocarbon acyl, C1-C6 hydrocarbon alkoxycarbonyl, C1-C6 hydrocarbon amide on the (hetero)aromatic ring Acyl; acyl of C0-C8 hydrocarbon; carboxyl; ester carbonyl substituted by C1-C12 hydrocarbon or (hetero)aryl; amide carbonyl substituted by C1-C12 hydrocarbon or (hetero)aryl; vinyl substituted by fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C4 hydrocarbon, (hetero)aryl, C1-C8 hydrocarbon alkoxycarbonyl, C1-C8 hydrocarbon and (hetero)aryl amide, sulfonic acid group on double bond; Ethylene groups substituted with fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C4 hydrocarbon, (hetero)aryl, C1-C8 hydrocarbon alkoxycarbonyl, C1-C8 hydrocarbon and (hetero)arylamide, or sulfonic acid; allyl groups substituted with fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C4 hydrocarbon, (hetero)aryl, C1-C8 hydrocarbon alkoxycarbonyl, C1-C8 hydrocarbon and (hetero)arylamide, or sulfonic acid on the double bond; R 2 The benzyl ring is connected with fluorine, chlorine, bromine, iodine, nitro, cyano, carboxyl, sulfonic acid, aldehyde, C1-C8 hydrocarbon, C1-C6 hydrocarbon acyl, C1-C6 hydrocarbon alkoxycarbonyl, C1-C6 hydrocarbon amide substituted benzyl; the double bond is connected with fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C4 hydrocarbon, (hetero)aryl, C1-C8 hydrocarbon alkoxycarbonyl, C1-C8 hydrocarbon Allyl substituted with nitro, cyano, sulfonic acid, carboxyl, C1-C8 hydrocarbon alkoxycarbonyl, C1-C8 alkyl and (hetero)aryl amide, and sulfonic acid; methylene substituted with nitro, cyano, sulfonic acid, carboxyl, C1-C8 hydrocarbon alkoxycarbonyl, C1-C8 alkyl and (hetero)aryl amide; propargyl substituted with fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C4 hydrocarbon, (hetero)aryl, C1-C8 hydrocarbon alkoxycarbonyl, C1-C8 hydrocarbon and (hetero)aryl amide, and sulfonic acid; R 3 It is hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, cyclohexyl, benzyl, phenyl, aryl with substituents on the benzene ring, and heteroaryl with substituents. The substituents on the (hetero)aryl are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, cyclohexyl, aryl, alkoxy, alkylthio, C1-C6 alkoxy ester, C1-C6 alkyl substituted amide, aldehyde, cyano, nitro, fluorine, chlorine, bromine, iodine, allyl, sulfonic acid, carboxyl, benzyl. The heteroaryl is pyridine, furan, thiophene, thiazole, oxazole, pyridazine, etc. The number of substituents on the (hetero)aryl is 1-5.

2. The method for preparing a 5-hydroxy-3-alkylthio-2-cyclopentenone derivative according to claim 1, characterized in that the method comprises the following steps: Add α-enoyl dithioacetal compound, Selectfluor, water and solvent into a reactor, seal it and react it at 60-120° C. for 2-24 hours in a nitrogen atmosphere to obtain a 5-hydroxy-3-alkylthio-2-cyclopentenone derivative; in, The molar dosage of α-enoyl disulfide ketene compound: Selectfluor: H2O is 1: 0.8-2.0: 0.1-3.0; The α-enoyl disulfide ketene compound is represented by the following general formula: Among them, R 1 is a hydrogen atom; various C1-C12 hydrocarbon groups; fluorine, chlorine, bromine, iodine; nitro; cyano; benzyl substituted with fluorine, chlorine, bromine, iodine, nitro, cyano, carboxyl, sulfonic acid, aldehyde, C1-C8 hydrocarbon group, C1-C6 hydrocarbon acyl group, C1-C6 hydrocarbon alkoxycarbonyl group, C1-C6 hydrocarbon amide; (hetero) aromatic rings with fluorine, chlorine, bromine, iodine, nitro, cyano, carboxyl, sulfonic acid, (hetero)aryl substituted with aldehyde, C1-C8 hydrocarbon, C1-C6 hydrocarbon acyl, C1-C6 hydrocarbon alkoxycarbonyl, C1-C6 hydrocarbon amide; (hetero)aryl substituted with fluorine, chlorine, bromine, iodine, nitro, cyano, carboxyl, sulfonic acid, aldehyde, C1-C8 hydrocarbon, C1-C6 hydrocarbon acyl, C1-C6 hydrocarbon alkoxycarbonyl, C1-C6 hydrocarbon amide on the (hetero)aromatic ring Acyl; acyl of C0-C8 hydrocarbon; carboxyl; ester carbonyl substituted by C1-C12 hydrocarbon or (hetero)aryl; amide carbonyl substituted by C1-C12 hydrocarbon or (hetero)aryl; vinyl substituted by fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C4 hydrocarbon, (hetero)aryl, C1-C8 hydrocarbon alkoxycarbonyl, C1-C8 hydrocarbon and (hetero)aryl amide, sulfonic acid group on double bond; Ethylene groups substituted with fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C4 hydrocarbon, (hetero)aryl, C1-C8 hydrocarbon alkoxycarbonyl, C1-C8 hydrocarbon and (hetero)arylamide, or sulfonic acid; allyl groups substituted with fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C4 hydrocarbon, (hetero)aryl, C1-C8 hydrocarbon alkoxycarbonyl, C1-C8 hydrocarbon and (hetero)arylamide, or sulfonic acid on the double bond; R 2 The benzyl ring is connected with fluorine, chlorine, bromine, iodine, nitro, cyano, carboxyl, sulfonic acid, aldehyde, C1-C8 hydrocarbon, C1-C6 hydrocarbon acyl, C1-C6 hydrocarbon alkoxycarbonyl, C1-C6 hydrocarbon amide substituted benzyl; the double bond is connected with fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C4 hydrocarbon, (hetero)aryl, C1-C8 hydrocarbon alkoxycarbonyl, C1-C8 hydrocarbon Allyl substituted with nitro, cyano, sulfonic acid, carboxyl, C1-C8 hydrocarbon alkoxycarbonyl, C1-C8 alkyl and (hetero)aryl amide, and sulfonic acid; methylene substituted with nitro, cyano, sulfonic acid, carboxyl, C1-C8 hydrocarbon alkoxycarbonyl, C1-C8 alkyl and (hetero)aryl amide; propargyl substituted with fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C4 hydrocarbon, (hetero)aryl, C1-C8 hydrocarbon alkoxycarbonyl, C1-C8 hydrocarbon and (hetero)aryl amide, and sulfonic acid; R 3 is hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, cyclohexyl, benzyl, phenyl, aryl with substituents on the benzene ring, and heteroaryl with substituents. The substituents on the (hetero)aryl are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, cyclohexyl, aryl, alkoxy, alkylthio, C1-C6 alkoxy ester, C1-C6 alkyl substituted amide, aldehyde, cyano, nitro, fluorine, chlorine, bromine, iodine, allyl, sulfonic acid, carboxyl, and benzyl. The heteroaryl is pyridine, furan, thiophene, thiazole, oxazole, pyridazine, etc. The number of substituents on the (hetero)aryl is 1-5; The solvent is: toluene, xylene, sulfolane, N,N-dimethylformamide, N,N-dimethylacetamide, anisole, chlorobenzene, dimethyl sulfoxide, 1,3-dimethyl-2-imidazolidinone, 1,4-dioxane, acetonitrile, butyronitrile, N-methylpyrrolidone, methyl tert-butyl ether, cyclohexanone, tetrahydrofuran, dichloroethane or dichloromethane.

3. The method for preparing a 5-hydroxy-3-alkylthio-2-cyclopentenone derivative according to claim 2, characterized in that: The method further comprises the following steps: pouring the obtained reaction solution into saturated saline to quench, then extracting with an extractant, drying the obtained organic phase with a desiccant, distilling and recovering the solvent, and separating and purifying the residue by silica gel column chromatography to complete the purification; The extractant is one or more of ethyl acetate, dichloromethane, n-hexane, cyclohexane, acetone, ethyl ether, n-butyl ether, cyclohexanone, ethyl propionate, butyl acetate, etc., and its volume is 2 to 4 times that of the reaction solvent; The desiccant is one or more of anhydrous magnesium sulfate, anhydrous sodium sulfate, calcium chloride, magnesium chloride, sodium carbonate, calcium hydroxide, etc.; In the separation and purification of the product, the eluent used for column chromatography is one or more of petroleum ether, n-hexane, cyclohexane, acetone, acetonitrile, methanol, ethanol, acetic acid, ethyl acetate, toluene, benzene, triethylamine, dichloromethane, chloroform, etc.

4. The method for preparing a 5-hydroxy-3-alkylthio-2-cyclopentenone derivative according to claim 2, characterized in that: 0.2-1.0 mmol of α-enoyl disulfide ketene compound is added for every 2-5 ml of solvent.

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