Preparation method of 4-cyclopentene-1, 3-diketone and 4-cyclopentene-1, 3-diketone

Abstract

The invention provides a preparation method of 4-cyclopentene-1, 3-diketone and the 4-cyclopentene-1, 3-diketone, and relates to the technical field of organic synthesis. The invention discloses a preparation method of 1, 4-cyclopentene-1, 3-diketone, which is obtained by reacting reaction raw materials consisting of 5-hydroxymethylfurfural, water, a catalyst and an oxidizing agent, the catalyst is selected from acid catalysts. According to the invention, water can be used as a reaction solvent, and 4-cyclopentene-1, 3-diketone can be obtained from HMF under the action of an acid catalyst and an oxidizing agent under relatively mild conditions.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis and relates to a preparation method of 4-cyclopentene-1,3-dione and 4-cyclopentene-1,3-dione. Background Art

[0002] Cyclopentenone derivatives are of great value in the field of medicine. 4-Cyclopentene-1,3-dione, as a key compound among them, has shown the effects of inhibiting cell proliferation and inducing apoptosis in a variety of cancer cells, and is an important intermediate for contemporary anti-cancer and anti-inflammatory drugs. At room temperature, 4-cyclopentene-1,3-dione appears as light brown or dark brown crystals. Currently, 4-cyclopentene-1,3-dione is usually prepared by oxidation using petroleum-based raw materials such as cyclopentene, 2,5-dibromocyclopentene, 2,5-diolcyclopentene, etc. as starting materials, and using precious metals or environmentally unfriendly chromium trioxide as catalysts. Chinese patent CN111253231A discloses a method for preparing 4-cyclopentene-1,3-dione by oxidation using 5-hydroxymethylfurfural (HMF) as a raw material. The method requires a closed reaction at high temperature, requires the use of a pressure-resistant reactor, and has a long reaction time, which is not conducive to industrial mass production. Moreover, when an organic solvent is used as the reaction solvent, persulfate is insoluble in the organic solvent, resulting in poor oxidation reaction effect. Summary of the Invention

[0003] In order to solve the above technical problems, the present invention provides a preparation method of 4-cyclopentene-1,3-dione and 4-cyclopentene-1,3-dione.

[0004] The technical solutions of the present invention are as follows:

[0005] A method for preparing 4-cyclopentene-1,3-dione, which is obtained by reacting reaction raw materials consisting of 5-hydroxymethylfurfural, water, a catalyst and an oxidant;

[0006] The catalyst is selected from acid catalysts.

[0007] Preferably, the concentration of the 5-hydroxymethylfurfural in the reaction raw materials is 5-25 wt%.

[0008] Preferably, the acid catalyst is selected from one or a combination of two or more of an inorganic acid, an organic acid and a solid acid.

[0009] Preferably, the acid catalyst is selected from one or a combination of two or more of sulfuric acid, hydrochloric acid, benzenesulfonic acid, trifluoromethylbenzenesulfonic acid, formic acid and strong acidic cation exchange resin.

[0010] Preferably, the oxidant is selected from one or a combination of two or more of hydrogen peroxide, urea peroxide, hydrogen persulfate, hypochlorite and trichloroisocyanuric acid.

[0011] Preferably, the molar ratio of the 5-hydroxymethylfurfural, the catalyst and the oxidant is 1:0.05-0.25:1-4.

[0012] Preferably, the reaction temperature is 25-100° C., and the reaction time is 0.5-8 h.

[0013] Preferably, the reaction further includes post-treatment: the reaction liquid after the reaction is extracted with an organic solvent to obtain an extract; the organic solvent is removed from the extract to obtain the 4-cyclopentene-1,3-dione.

[0014] More preferably, the organic solvent is slightly soluble in water or insoluble in water at 25°C.

[0015] A 4-cyclopentene-1,3-dione prepared by the preparation method described in any one of the above embodiments.

[0016] The beneficial effects of the present invention are: in the present invention, HMF is converted into 4-cyclopentene-1,3-dione under the action of an acid catalyst and an oxidant, the reaction conditions are milder, the reaction temperature is lower, the reaction time is shorter, and the reaction can be carried out under normal pressure. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 This is the GC spectrum of the 4-cyclopentene-1,3-dione standard sample.

[0018] Figure 2 This is the GC spectrum of 4-cyclopentene-1,3-dione obtained in Example 3. DETAILED DESCRIPTION

[0019] The technical solution of the present invention is further illustrated and described below through specific implementation methods.

[0020] In one aspect, the present invention provides a method for preparing 4-cyclopentene-1,3-dione, which is obtained by reacting reaction raw materials consisting of 5-hydroxymethylfurfural, water, a catalyst and an oxidant;

[0021] The catalyst is selected from acid catalysts.

[0022] This method uses water as the reaction solvent. Under the action of an acid catalyst and an oxidant, HMF is converted into 4-cyclopentene-1,3-dione. This can be achieved at normal pressure, eliminating the need for enclosed equipment. Furthermore, using water as the reaction solvent is more environmentally friendly, safer, and less expensive than using organic solvents.

[0023] In some embodiments, the concentration of 5-hydroxymethylfurfural in the reaction raw materials is 5-25wt%. For example, the concentration of 5-hydroxymethylfurfural can be any value of 5wt%, 7wt%, 8wt%, 10wt%, 12wt%, 15wt%, 17wt%, 18wt%, 20wt%, 22wt%, 23wt%, 25wt%, etc.

[0024] In some embodiments, the acid catalyst is selected from one or a combination of two or more of an inorganic acid, an organic acid, and a solid acid. Inorganic acids include sulfuric acid and hydrochloric acid; organic acids include benzenesulfonic acid, trifluoromethylbenzenesulfonic acid, and formic acid; and solid acids include a strongly acidic cation exchange resin, such as Amberlyst 15 ion exchange resin.

[0025] In some embodiments, the oxidant is selected from one or a combination of two or more of hydrogen peroxide, urea peroxide, hydrogen persulfate, hypochlorite, and trichloroisocyanuric acid. The oxidant has good water solubility or is soluble in water within the usage amount range to oxidize HMF.

[0026] In some embodiments, the molar ratio of 5-hydroxymethylfurfural, the catalyst and the oxidant is 1:0.05-0.25:1-4. For example, the molar ratio can be any value in 1:0.05:1, 1:0.05:2, 1:0.05:3, 1:0.05:4, 1:0.1:2, 1:0.15:2, 1:0.2:2, 1:0.25:2, 1:0.1:3, 1:0.15:3, 1:0.2:3, 1:0.25:3, 1:0.1:2, 1:0.15:4, 1:0.2:4, 1:0.25:4, etc., or any value in between, without particular limitation. In the above molar ratios, the molar amount of the catalyst refers to the actual molar amount of the acid therein. For example, if the catalyst is sulfuric acid, the actual molar amount of 5 mmol of 40 mol% sulfuric acid is 2 mmol, the actual molar amount of 10 mmol of 10 mol% hydrochloric acid is 1 mmol, and so on. In the above molar ratios, the molar amount of the oxidant refers to the actual molar amount of the oxidant therein. For example, in 30% hydrogen peroxide, the molar amount refers to the molar amount of hydrogen peroxide therein.

[0027] In some embodiments, the reaction temperature is 25-100° C., and the reaction time is 0.5-8 hours. For example, the reaction temperature can be any value of 25° C., 35° C., 45° C., 50° C., 65° C., 75° C., 80° C., 90° C., 100° C., etc., and the reaction time can be any value of 0.5 hours, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, etc. Further, the reaction temperature can be 25-80° C., and the reaction time can be 1-6 hours.

[0028] In some embodiments, the reaction further includes post-processing: the reaction solution is extracted with an organic solvent to obtain an extract; the organic solvent is removed from the extract to obtain 4-cyclopentene-1,3-dione. The reaction product, 4-cyclopentene-1,3-dione, is well soluble in organic solvents, particularly polar organic solvents. However, the reaction raw materials, such as HMF, catalyst, and oxidant, have high solubility in the aqueous phase. Therefore, extraction with an organic solvent allows the product to be extracted into the organic phase, while a small amount of unreacted HMF (if present), oxidant (if present), acid catalyst, etc., remains in the aqueous phase. The organic solvent in the organic phase is then removed to obtain 4-cyclopentene-1,3-dione.

[0029] In some embodiments, the organic solvent is slightly soluble or insoluble in water at 25° C., and can effectively dissolve the extracted product 4-cyclopentene-1,3-dione and separate it from the aqueous phase. For example, the organic solvent can be ethyl acetate, butyl acetate, n-butanol, dichloromethane, chloroform, carbon tetrachloride, acetonitrile, dimethyl carbonate, etc.

[0030] On the other hand, the present invention also provides 4-cyclopentene-1,3-dione, which is prepared by the preparation method described in any one of the above embodiments.

[0031] The technical solution of the present invention is further described and illustrated below based on various embodiments.

[0032] Example 1

[0033] 5 mmol of 40 mol% sulfuric acid was added to a 50 mL round-bottom flask. 0.01 mol of 5-hydroxymethylfurfural was then dissolved in 20 mL of deionized water and added to the flask with stirring along with 0.05 mol of 30 wt% hydrogen peroxide. After all the ingredients were added, the mixture was reacted at 75°C under normal pressure for 2 hours. The reaction solution was cooled to room temperature and extracted with 40 mL of dichloromethane. The organic phase was separated and the dichloromethane was removed by distillation to obtain a light yellow 4-cyclopentene-1,3-dione solid. Gas chromatography (GC) analysis revealed a 96% HMF conversion and a 67% 4-cyclopentene-1,3-dione yield.

[0034] Comparative Example 1

[0035] This comparative example differs from Example 1 in that, in Example 1, 40 mol% sulfuric acid was not added. The remaining steps remained unchanged. The measured HMF conversion was 29%, and the yield of 4-cyclopentene-1,3-dione was 17%.

[0036] Example 2

[0037] This example differs from Example 1 in that the reaction time in Example 1 was adjusted from 2 hours to 4 hours. The remaining steps remained unchanged. The measured HMF conversion exceeded 99%, and the yield of 4-cyclopentene-1,3-dione was 75%.

[0038] Example 3

[0039] This example differs from Example 1 in that the 30 wt% hydrogen peroxide in Example 1 was adjusted from 0.05 mol to 0.1 mol. The remaining steps remained unchanged. The measured HMF conversion exceeded 99%, and the yield of 4-cyclopentene-1,3-dione was 85%.

[0040] The gas chromatography (GC) spectrum of 4-cyclopentene-1,3-dione standard is shown in the attached figure. Figure 1 The GC spectrum of 4-cyclopentene-1,3-dione obtained in this embodiment is shown in the attached Figure 2 shown.

[0041] Example 4

[0042] This example differs from Example 3 in that the reaction time in Example 3 was adjusted from 2 hours to 6 hours. The remaining steps remained unchanged. The measured HMF conversion exceeded 99%, and the yield of 4-cyclopentene-1,3-dione was 88%.

[0043] Example 5

[0044] This example differs from Example 3 in that the concentration of 40 mol% sulfuric acid in Example 3 was adjusted from 5 mmol to 2 mmol. The remaining steps remained unchanged. The measured HMF conversion was 95%, and the yield of 4-cyclopentene-1,3-dione was 74%.

[0045] Example 6

[0046] This example differs from Example 5 in that the reaction time in Example 5 was adjusted from 2 hours to 4 hours. The remaining steps remained unchanged. The measured HMF conversion exceeded 99%, and the yield of 4-cyclopentene-1,3-dione was 83%.

[0047] Example 7

[0048] 5 mmol of 40 mol% sulfuric acid was added to a 50 mL round-bottom flask, followed by dissolving 0.01 mol of 5-hydroxymethylfurfural in 20 mL of deionized water. The mixture was then added to the flask with stirring along with 0.02 mol of urea peroxide. After all the ingredients were added, the mixture was reacted at 75°C under normal pressure for 2 hours. The reaction solution was cooled to room temperature, extracted with 40 ml of dichloromethane, and the organic phase was separated. The dichloromethane was then distilled off from the organic phase to obtain a light yellow 4-cyclopentene-1,3-dione solid. Gas chromatography (GC) analysis showed that the HMF conversion exceeded 99%, and the 4-cyclopentene-1,3-dione yield was 85%.

[0049] Example 8

[0050] This example differs from Example 7 in that, in Example 7, urea peroxide was replaced with an equimolar amount of potassium persulfate. The remaining steps remained unchanged. The measured HMF conversion was 95%, and the yield of 4-cyclopentene-1,3-dione was 74%.

[0051] Example 9

[0052] This example differs from Example 7 in that urea peroxide in Example 7 was replaced with 0.12 mol of 10 wt% sodium hypochlorite. The remaining steps remained unchanged. The measured HMF conversion was 98%, and the yield of 4-cyclopentene-1,3-dione was 80%.

[0053] Example 10

[0054] This example differs from Example 7 in that urea peroxide was replaced with 0.02 mol of trichloroisocyanuric acid in Example 7. The remaining steps remained unchanged. The measured HMF conversion exceeded 99%, and the yield of 4-cyclopentene-1,3-dione was 78%.

[0055] Example 11

[0056] First, 5 mmol of 20 mol% hydrochloric acid was added to a 50 mL round-bottom flask, followed by dissolving 0.01 mol of 5-hydroxymethylfurfural in 20 mL of deionized water. The mixture was then slowly added to the flask together with 0.06 mol of 30 wt% hydrogen peroxide under stirring. After all the additions were completed, the reaction was carried out at 75°C for 2 hours. The reaction solution was cooled to room temperature and extracted with 40 ml of dichloromethane. The organic phase was separated and dichloromethane was removed by distillation to obtain a light yellow 4-cyclopentene-1,3-dione solid. The HMF conversion rate was measured to be over 99%, and the yield of 4-cyclopentene-1,3-dione was 90%.

[0057] Example 12

[0058] This example differs from Example 11 in that the concentration of 20 mol% hydrochloric acid in Example 11 was adjusted from 5 mmol to 2.5 mmol. The remaining steps remained unchanged. The measured HMF conversion was 98%, and the yield of 4-cyclopentene-1,3-dione was 83%.

[0059] Example 13

[0060] The difference between this example and Example 11 is that in Example 11, the reaction time was adjusted from 2 hours to 3 hours. The remaining steps remained unchanged. The measured HMF conversion rate exceeded 99%, and the yield of 4-cyclopentene-1,3-dione was 92%.

[0061] Example 14

[0062] This example differs from Example 11 in that 5 mmol of 20 mol% hydrochloric acid in Example 11 was replaced with 5 mmol of formic acid. The remaining steps remained unchanged. The measured HMF conversion was 97%, and the yield of 4-cyclopentene-1,3-dione was 87%.

[0063] Example 15

[0064] 0.01 mol of 5-hydroxymethylfurfural was dissolved in 20 mL of deionized water in a 50 mL round-bottom flask, and 0.2 g of Amberlyst 15 cation exchange resin was added with stirring. The mixture was stirred for 2 minutes, and then 0.07 mol of 30 wt% hydrogen peroxide was slowly added. After all the materials were added, the reaction was carried out at 75°C under normal pressure for 2 hours. Heating was stopped, and the reaction solution was cooled to room temperature. It was extracted with 40 mL of dichloromethane, and the organic phase was separated. The dichloromethane was distilled from the organic phase to obtain a light yellow solid, which was 4-cyclopentene-1,3-dione. The HMF conversion rate exceeded 99%, and the yield of 4-cyclopentene-1,3-dione was 82%.

[0065] Example 16

[0066] 5 mmol of 40 mol% sulfuric acid was added to a 50 mL round-bottom flask. 0.01 mol of 5-hydroxymethylfurfural was then dissolved in 20 mL of deionized water and added to the flask with stirring along with 0.07 mol of 30% hydrogen peroxide. After all the ingredients were added, the mixture was reacted at 25°C under normal pressure for 5 hours. 40 mL of dichloromethane was added for extraction, and the organic phase was separated and dichloromethane was removed by distillation to obtain a light yellow 4-cyclopentene-1,3-dione solid. Gas chromatography (GC) analysis showed an HMF conversion of over 99% and an 85% yield of 4-cyclopentene-1,3-dione.

[0067] Example 17

[0068] This example differs from Example 16 in that the reaction temperature in Example 16 was adjusted from 25°C to 45°C, and the reaction temperature was cooled to room temperature after the reaction. The remaining steps remained unchanged. The measured HMF conversion exceeded 99%, and the yield of 4-cyclopentene-1,3-dione was 89%.

[0069] As described above, the basic principles, main features, and advantages of the present invention are shown and described. Those skilled in the art should understand that the present invention is not limited to the above-described embodiments. The above-described embodiments are merely preferred embodiments of the present invention and are not intended to limit the scope of the present invention. In other words, equivalent changes and modifications made within the scope of the present invention and the contents of the specification should still fall within the scope of the present invention. The scope of protection claimed in the present invention is defined by the appended claims and their equivalents.

Claims

1. A method for preparing 4-cyclopentene-1,3-dione, characterized in that: The method is obtained by reacting reaction raw materials consisting of 5-hydroxymethylfurfural, water, a catalyst and an oxidant; The catalyst is selected from acid catalysts.

2. The preparation method according to claim 1, characterized in that The concentration of the 5-hydroxymethylfurfural in the reaction raw materials is 5-25 wt %.

3. The preparation method according to claim 1, characterized in that The acid catalyst is selected from one or a combination of two or more of inorganic acid, organic acid and solid acid.

4. The preparation method according to claim 1, characterized in that The acid catalyst is selected from one or a combination of two or more of sulfuric acid, hydrochloric acid, benzenesulfonic acid, trifluoromethylbenzenesulfonic acid, formic acid and strong acidic cation exchange resin.

5. The preparation method according to claim 1, characterized in that The oxidant is selected from one or a combination of two or more of hydrogen peroxide, urea peroxide, hydrogen persulfate, hypochlorite and trichloroisocyanuric acid.

6. The preparation method according to claim 1, characterized in that The molar ratio of the 5-hydroxymethylfurfural, the catalyst and the oxidant is 1:0.05-0.25:1-4.

7. The preparation method according to claim 1, characterized in that The reaction temperature is 25-100° C., and the reaction time is 0.5-8 h.

8. The preparation method according to claim 1, characterized in that The reaction further includes post-processing: the reaction liquid after the reaction is extracted with an organic solvent to obtain an extract; the organic solvent is removed from the extract to obtain the 4-cyclopentene-1,3-dione.

9. The preparation method according to claim 8, characterized in that The organic solvent is slightly soluble in water or insoluble in water at 25°C.

10. 4-cyclopentene-1,3-dione, characterized in that The invention is prepared by the preparation method according to any one of claims 1 to 9.

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