A method for preparing thiophene ester compounds from levulinic acid ester compounds

Abstract

The present application provides a method for preparing a propionic acid ester thiofuran ester compound from a levulinic acid ester compound, comprising the following steps: reacting a compound 1 and a sulfur reagent in the presence of a catalyst to obtain a compound 2; wherein, R 2 and R 3 are each independently hydrogen, alkyl, ROC(=O)‑(CH2)2‑ or aryl; R 1 is hydrogen, alkyl or aryl; R is each independently alkyl or aryl; and m is independently 1 or 2. The present application provides a method for preparing a thiofuran ester compound from a levulinic acid ester compound, which uses a biomass-based levulinic acid ester compound as a starting material, is prepared through a condensation thio reaction, and is separated and purified through column chromatography to obtain the thiofuran ester compound. The preparation method provided by the present application has the advantages of low cost, high efficiency, green environmental protection, sustainability, mild preparation process conditions, simple separation and purification, and high application potential of the obtained product in the fields of medicine, essence, plasticizer, battery and the like.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of chemical industry, and particularly provides a method for preparing a thiophene ester compound from a levulinic acid ester compound. BACKGROUND

[0002] At present, the thiophene chemicals (such as thiophene ester compounds) prepared in the industry are all derived from fossil resources such as petroleum, and thiophene diacetic acid (ester) and thiophene dipropionic acid (ester) are usually synthesized from thiophene raw materials through a complex alkylation reaction. Such compounds have similar structures and properties to valuable thiophene raw materials and intermediates in the pharmaceutical, plasticizer, battery and other industries, and have high application potential.

[0003] There are many studies on them in the prior art. For example, Chinese patent CN105609876 A discloses a thiophene ester compound electrolyte additive and a high-voltage electrolyte containing the electrolyte additive, wherein the high-voltage electrolyte component applied includes a thiophene ester compound, and the mass of the thiophene ester compound used is 3% to 8% of the mass of the high-voltage electrolyte. Chinese patent CN116514768 A discloses a 2,5-thiophene dicarboxylic acid ester plasticizer, a preparation method and application thereof, wherein the 2,5-thiophene dicarboxylic acid ester plasticizer prepared from renewable resource 2,5-thiophene dicarboxylic acid has excellent comprehensive performance. Chinese patent CN113735820 A discloses a preparation process of 2,5-thiophene dicarboxylic acid, wherein an important intermediate is thiophene-3,4-dicarboxylic acid 3-ethyl ester 4-methyl ester. Chinese patent CN114085218 A discloses a coumarin-based two-photon initiator, a synthesis method and application thereof, wherein the most important intermediate is 2,5-diethyl acetoacetate-based thiophene. Chinese patents CN111205266 A, CN115160290 A and CN114605375 A disclose a synthesis method of 2-thiophene acetic acid, and the products of the above patents are 2-thiophene acetic acid. International patent WO2020094634 A1 discloses nalorphine prodrugs for long-acting injection compositions and related methods, which include a synthesis method of 2,5-thiophene diacetic acid, 2,5-thiophene dipropionic acid and the like.

[0004] The levulinic acid ester compound is a platform compound that can be prepared from lignocellulose through acid catalytic degradation. However, there is no known patent or literature reporting a method for preparing a thiophene ester compound from a biomass-based levulinic acid ester compound.

[0005] Therefore, it is necessary to provide a method for preparing a thiophene ester compound from a biomass-based levulinic acid ester compound, so as to maintain its advantages of low cost, high efficiency, green environmental protection and sustainability. SUMMARY

[0006] To achieve the objectives of this invention, we provide a method for preparing thiophene esters from levulinate compounds. The method uses biomass-based levulinate compounds as starting materials, prepares them via a condensation thiolation reaction, and then purifies them by column chromatography to obtain the thiophene esters. The preparation method provided by this invention has the advantages of low cost, high efficiency, environmental friendliness, and sustainability. Furthermore, the preparation process is mild, and the separation and purification are simple. The obtained products have high application potential in multiple fields such as pharmaceuticals, fragrances, plasticizers, and batteries.

[0007] To achieve the above objectives, the technical solution of the present invention is as follows:

[0008] On one hand, the present invention provides a method for preparing thiophene ester compounds from levulinate compounds, comprising the following steps:

[0009]

[0010] Compound 1 and a sulfur reagent reacted under the action of a catalyst to prepare compound 2;

[0011] Among them, R 2 and R 3 Each can be independently hydrogen, alkyl, ROC(=O)-(CH2)2- or aryl;

[0012] R 1 It can be hydrogen, alkyl, or aryl;

[0013] R can be alkyl or aryl independently;

[0014] m can be 1 or 2 independently.

[0015] Furthermore, the R 2 and R 3 Each independently is hydrogen, C 1-6 Alkyl, ROC(=O)-(CH2)2- or C 6-12 Aryl.

[0016] Furthermore, the R 1 For hydrogen, C 1-6 Alkyl or C 6-12 Aryl.

[0017] Furthermore, each of the R's is independently C. 1-6 Alkyl or C 6-12 Aryl.

[0018] Furthermore, the sulfur reagent is elemental sulfur, iron sulfide, or pyrite powder.

[0019] Further, the catalyst is selected from at least one of acidic catalysts and basic catalysts. Preferably, the basic catalyst is an organic amine reagent. Further, the organic amine reagent is selected from one or more of p-phenylenediamine, aniline, cysteine, glycine, diglycinate, and ethylenediamine. Preferably, the acidic catalyst is one or more of p-toluenesulfonic acid monohydrate (PTSA.H2O reagent), p-toluenesulfonic acid, aminosulfonic acid, methanesulfonic acid, trifluoromethanesulfonic acid, or sulfonic acid ion exchange resin.

[0020] Examples of "alkyl" as used in this invention include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, sec-butyl, n-pentyl, and n-hexyl. "alkyl" may further include various heteroatoms (e.g., O, N, S, Si, or P) or halogen atoms (e.g., F, Cl, Br). The aryl groups described in this invention may be monocyclic, fused to form bicyclic or tricyclic groups, or linked by bonds to form biaryl groups. Representative aryl groups include phenyl, naphthyl, and biphenyl. Other aryl groups include benzyl with a methylene linking group.

[0021] Further, the molar ratio of the sulfur reagent (e.g., elemental sulfur) to compound 1 is 0.5 to 3, preferably 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, or 3.

[0022] Further, the molar ratio of the organic amine reagent (e.g., aniline) to compound 1 is 0.5 to 1.5, preferably 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4 or 1.5.

[0023] Further, the acidic catalyst is p-toluenesulfonic acid (PTSA reagent) or a sulfonic acid ion exchange resin. Preferably, the PTSA reagent is p-toluenesulfonic acid monohydrate. Further, the molar ratio of the PTSA reagent to compound 1 is 0.01 to 0.3, preferably 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.11, 0.12, 0.13, 0.14, 0.15, 0.16, 0.17, 0.18, 0.19, 0.2, 0.21, 0.22, 0.23, 0.24, 0.25, 0.26, 0.27, 0.28, 0.29, or 0.3.

[0024] Further, the reaction may or may not be carried out in a solvent. Preferably, the solvent is selected from weakly polar aprotic solvents, such as one or a mixture of two of toluene, ethylbenzene, and p-xylene, with toluene being preferred. Further, the concentration of the acetylacetic ester compound in the solvent is 0.03–0.2 g / mL, preferably 0.03–0.17 g / mL, for example 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.11, 0.12, 0.14, 0.15, or 0.16 g / mL.

[0025] Furthermore, the reaction is carried out in a specific atmosphere, which is either an air atmosphere or a nitrogen atmosphere.

[0026] Furthermore, the reaction is carried out under a heating environment, and the heating reaction temperature is 90–140°C.

[0027] Furthermore, the reaction time is 10–35 h, preferably 12–32 h.

[0028] Furthermore, after the reaction is completed, the mixture is cooled to room temperature and then further separated and purified to obtain thiophene ester compounds.

[0029] Further, the separation and purification process includes acid washing, vacuum distillation, and column chromatography. Further, the acid washing involves washing the reaction mixture with a dilute hydrochloric acid solution of 8%–15% by mass, the volume of which is 1–3 times the volume of the reaction mixture. Further, the specific conditions for vacuum distillation are: a vacuum degree of 22 torr and a temperature of 80°C.

[0030] Furthermore, the eluent used in the column chromatography separation is: V(n-hexane):V(dichloromethane):V(methanol) = 60-80:15-25:5-15.

[0031] Furthermore, compound 2 is selected from... One or two of them.

[0032] Furthermore, compound 2 is selected from... One or two of them.

[0033] Furthermore, when compound 2 is a mixture, it can be further purified by reverse-phase column chromatography and then separated by preparative supercritical fluid chromatography.

[0034] On one hand, the present invention provides a method for preparing thiophene ester compounds from acetylacetic ester compounds, comprising the following steps: reacting compound 1A, elemental sulfur reagent, aniline reagent and PTSA·H2O reagent; cooling the reaction mixture and then separating it by acid washing, vacuum distillation and column chromatography to obtain compound 2A and compound 2B.

[0035]

[0036] Further, compound 1A is dissolved in a solvent at a concentration of 0.03–0.17 g / mL. Based on the molar ratio of compound 1A, elemental sulfur reagent, aniline reagent, and PTSA·H2O reagent in a molar ratio of 0.5–3, 0.5–1.5, and PTSA·H2O reagent are added. The reaction mixture is then reacted at 90°C–140°C for 12–32 h under a nitrogen atmosphere or an air atmosphere at 1 bar to obtain a reaction mixture.

[0037] Further, after cooling the reaction mixture, it was washed with a dilute hydrochloric acid solution with a mass concentration of 8% to 15%, and then distilled under reduced pressure at a vacuum of 22 torr and 80°C. The residue was further separated by column chromatography to obtain a mixture of compound 2A and compound 2B.

[0038] Furthermore, the mixture of compound 2A and compound 2B is further purified by reversed-phase column chromatography and then separated by preparative supercritical fluid chromatography.

[0039] On the other hand, the present invention provides a thiophene ester compound prepared by the preparation method described above, with the following specific structure:

[0040]

[0041] In another aspect, the present invention provides the application of the thiophene ester compounds prepared by the preparation method described above in the preparation of valuable thiophene raw materials and intermediates in the pharmaceutical, fragrance, plasticizer, and battery industries.

[0042] The principle involved in this invention is as follows:

[0043] A levulinate compound (compound 1) reacts in a solvent with elemental sulfur, aniline, and PTSA·H₂O reagent. The carbonyl oxygen at position 4 of levulinate compound (compound 1) is replaced by aniline to form intermediate 1, which then undergoes an aldol condensation reaction with another levulinate compound (compound 1) to dehydrate and generate a dimer intermediate (intermediate 2). Intermediate 2 undergoes double bond isomerization and reacts with elemental sulfur to form a thiophene ring, which is then further decoupled from the aniline. Due to the two possible orientations of elemental sulfur attack, the resulting product is a mixture of 3-methyl-2-acetate-5-propionate thiophene (compound 2b') and 2,4-propionate thiophene (compound 2a').

[0044] The specific reaction principle is as follows:

[0045]

[0046] Beneficial effects:

[0047] This invention uses acetylacetic ester compounds derived from biomass-based lignocellulose and inexpensive and readily available elemental sulfur, a petrochemical byproduct, as raw materials, making the method of this invention sustainable and atom-economical.

[0048] The present invention uses acetylacetyl ester compounds, elemental sulfur, aniline reagent and PTSA reagent to prepare thiophene ester compounds (e.g. 3-methyl-2-acetyl-5-propionate thiophene and 2,4-propionate thiophene) in a one-step reaction through amination, dimerization, thiolation and cyclization processes. The system is simple and efficient.

[0049] The reaction mixture of the present invention is washed with dilute hydrochloric acid, which can effectively remove PTSA·H2O and aniline reagent without affecting the target product thiophene ester compounds (e.g., 3-methyl-2-acetyl-5-propionate thiophene and 2,4-propionate thiophene). PTSA·H2O and aniline are neutralized to form salts and transferred to the aqueous phase, while the target product thiophene ester compounds are still retained in the organic phase, effectively achieving the separation of the target product from the reaction system.

[0050] The organic phase obtained after acid washing of the reaction mixture of the present invention is separated by column chromatography after vacuum distillation to obtain a mixture of thiophene ester compounds with a total purity of more than 90%. The mixture is further purified by reversed-phase column chromatography and then separated by preparative supercritical fluid chromatography. The thiophene ester products prepared by the present invention all have functional groups such as thiophene ring and ester, and have high plasticity.

[0051] The reaction system of this invention is simple, efficient, environmentally friendly, and low-cost, providing an effective route for preparing thiophene ester compounds from biomass.

[0052] Thiophene esters can be applied, but are not limited to, the following areas:

[0053] Thiophene ester compound electrolyte additive (CN105609876B) is used in high-voltage electrolytes.

[0054] Thiophene insecticides (CN1217578C) are used in photoactivated insecticides.

[0055] In summary, this invention is the first to propose a method for preparing 3-methyl-2-acetate-5-propionate thiophene and 2,4-propionate thiophene from biomass-based acetylacetates via intermolecular polymerization and thiolation, as well as a method for separation and purification, providing a novel preparation route for downstream chemicals of biomass-based renewable thiophene esters.

[0056] The present invention will be further illustrated below with reference to specific embodiments. These embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Attached Figure Description

[0057] Figure 1 GC-MS spectrum of the product obtained by tandem thiolation of methyl levulinate in the presence of elemental sulfur.

[0058] Figure 2 3-Methyl-2-acetic acid methyl 5-propionate methyl thiophene 1 H-NMR spectrum (solvent is deuterated chloroform).

[0059] Figure 3 3-Methyl-2-acetic acid methyl 5-propionate methyl thiophene 13 C10-NMR spectrum (solvent: deuterated chloroform).

[0060] Figure 4 2,4-Methyl propionate thiophene 1 H-NMR spectrum (solvent is deuterated chloroform).

[0061] Figure 5 2,4-Methyl propionate thiophene 13 C10-NMR spectrum (solvent: deuterated chloroform). Detailed Implementation

[0062] The present invention will be further illustrated below with reference to specific embodiments. These embodiments are for illustrative purposes only and are not intended to limit the scope of the invention.

[0063] Example 1

[0064] 10.14 g of methyl levulinate was added to 120 mL of toluene, along with 1.5 times the amount of elemental sulfur reagent, 1.1 times the amount of aniline reagent, and 0.15 times the amount of PTSA·H₂O reagent. The mixture was reacted at 140 °C and 1 bar in air for 24 h to obtain a dark brown oily substance. The residue was washed with 3 times its volume of 10% dilute hydrochloric acid solution, distilled under reduced pressure, and NMR quantification showed that the yields of 3-methyl-2-acetate methyl 5-propionate methyl thiophene and 2,4-propionate methyl thiophene were 12% and 18%, respectively.

[0065] Example 2

[0066] 0.65 g of methyl levulinate was mixed with 1.5 times the amount of elemental sulfur reagent, 2 times the amount of aniline reagent, and 0.15 times the amount of PTSA·H₂O reagent. The mixture was reacted for 24 h at 140 °C and 1 bar in air without solvent to obtain a dark brown oily substance. The residue was washed with 2.5 times its volume of 10% dilute hydrochloric acid solution, and then distilled under reduced pressure. Quantitative NMR analysis revealed that the yields of 3-methyl-2-acetate methyl-5-propanoate methylthiophene and 2,4-propanoate methylthiophene were 10% and 2%, respectively.

[0067] Example 3

[0068] 0.65 g of methyl levulinate was added to 8 mL of toluene, along with two times the amount of elemental sulfur reagent, 1.1 times the amount of aniline reagent, and 0.10 times the amount of PTSA·H₂O reagent. The mixture was reacted at 140 °C under a nitrogen atmosphere of 1 bar for 16 h to obtain a dark brown oily substance. The residue was washed with two volumes of 15% dilute hydrochloric acid solution, distilled under reduced pressure, and NMR quantification showed that the yields of 3-methyl-2-acetate methyl-5-propanoate methylthiophene and 2,4-propanoate methylthiophene were 7% and 1%, respectively.

[0069] Example 4

[0070] 10.14 g of methyl levulinate was added to 120 mL of toluene, along with 1.5 times the amount of elemental sulfur reagent, 1.1 times the amount of aniline reagent, and 0.10 times the amount of PTSA·H₂O reagent. The mixture was reacted at 140 °C and 1 bar in air for 24 h to obtain a dark brown oily substance. The residue was washed with 3 times its volume of 15% dilute hydrochloric acid solution, distilled under reduced pressure, and NMR quantification showed that the yields of 3-methyl-2-acetate methyl-5-propanoate methylthiophene and 2,4-propanoate methylthiophene were 11% and 17%, respectively.

[0071] Example 5

[0072] 0.65 g of methyl levulinate was added to 15 mL of toluene, along with two times the amount of elemental sulfur reagent, 0.75 times the amount of aniline reagent, and 0.08 times the amount of PTSA·H₂O reagent. The mixture was reacted at 120 °C and 1 bar in air for 16 h to obtain a dark brown oily substance. The residue was washed with two volumes of 7.5% dilute hydrochloric acid solution, distilled under reduced pressure, and NMR quantification showed that the yields of 3-methyl-2-acetate methyl-5-propionate methylthiophene and 2,4-propionate methylthiophene were 7% and 1%, respectively.

[0073] Example 6

[0074] 10.14 g of methyl levulinate was added to 120 mL of toluene, along with 1.5 times the amount of elemental sulfur reagent, 1.5 times the amount of aniline reagent, and 0.25 times the amount of PTSA·H₂O reagent. The mixture was reacted at 140 °C under a nitrogen atmosphere of 1 bar for 24 h to obtain a dark brown oily substance. The residue was washed with 3 times its volume of 10% dilute hydrochloric acid solution, distilled under reduced pressure, and NMR quantification showed that the yields of 3-methyl-2-acetate methyl 5-propionate methyl thiophene and 2,4-propionate methyl thiophene were 12% and 17%, respectively.

[0075] Example 7

[0076] In 0.65 g of methyl levulinate, two times the amount of elemental sulfur reagent, 1.1 times the amount of aniline reagent, and 0.08 times the amount of PTSA·H₂O reagent were added to the mixture. The reaction was carried out at 140 °C and 1 bar in air for 24 h to obtain a dark brown oily substance. The residue was washed with 2.5 times its volume of 8% dilute hydrochloric acid solution, distilled under reduced pressure, and quantitatively calculated by NMR to yield 9% and 1% of 3-methyl-2-acetate methyl-5-propionate methylthiophene and 2,4-propionate methylthiophene, respectively.

[0077] Example 8

[0078] 0.26 g of methyl levulinate was added to 9 mL of a mixture of ethylbenzene and toluene (volume ratio 1:1), along with 1.25 times the amount of elemental sulfur reagent, 1.1 times the amount of aniline reagent, and 0.07 times the amount of PTSA·H₂O reagent. The mixture was reacted at 140 °C under a nitrogen atmosphere of 1 bar for 16 h to obtain a dark brown oily substance. The residue was washed with 3 times its volume of 10% dilute hydrochloric acid solution, distilled under reduced pressure, and NMR quantification showed that the yields of 3-methyl-2-acetate methyl 5-propanoate methyl thiophene and 2,4-propanoate methyl thiophene were 8% and 1%, respectively.

[0079] Example 9

[0080] 0.72 g of ethyl levulinate was added to 10 ml of toluene, along with 1.5 times the amount of elemental sulfur reagent, 0.55 times the amount of aniline reagent, and 0.075 times the amount of PTSA·H₂O reagent. The mixture was reacted at 140 °C and 1 bar in air for 18 h to obtain a dark brown oily substance. The residue was washed with 3 times its volume of 7.5% dilute hydrochloric acid solution, distilled under reduced pressure, and NMR quantification showed that the yields of 3-methyl-2-ethyl acetate-5-propionate ethyl thiophene and 2,4-propionate ethyl thiophene were 5% and 1%, respectively.

[0081] Example 10

[0082] 11.232 g of ethyl levulinate was added to 120 ml of toluene, along with 1.1 times the amount of elemental sulfur reagent, 1.15 times the amount of aniline reagent, and 0.15 times the amount of PTSA·H₂O reagent. The mixture was reacted at 140 °C and 1 bar in air for 16 h to obtain a dark brown oily substance. The residue was washed with 2.5 times its volume of 13% dilute hydrochloric acid solution, and then distilled under reduced pressure. Quantitative NMR analysis revealed that the yields of 3-methyl-2-ethyl acetate-5-propionate ethyl thiophene and 2,4-propionate ethyl thiophene were 5% and 8%, respectively.

[0083] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for preparing thiophene ester compounds from levulinate ester compounds, characterized in that, Includes the following steps: ； Compound 1 and a sulfur reagent reacted under the action of a catalyst to prepare compound 2; in, Compound 2 is selected from One or two of them; R 1 It can be hydrogen or methyl; R 3 It is hydrogen; R is independently C 1-6 alkyl; m can be 1 or 2 independently; The sulfur reagent is elemental sulfur; The catalyst is either an acidic catalyst or a basic catalyst; The alkaline catalyst is an organic amine reagent; the organic amine reagent is selected from p-phenylenediamine or aniline; the acidic catalyst is p-toluenesulfonic acid monohydrate or p-toluenesulfonic acid.

2. The preparation method according to claim 1, characterized in that, The molar ratio of the sulfur reagent to compound 1 is 0.5 to 3; The catalyst is an organic amine reagent and p-toluenesulfonic acid monohydrate; The molar ratio of the organic amine reagent to compound 1 is 0.5 to 1.5; The molar ratio of p-toluenesulfonic acid monohydrate to compound 1 is 0.01 to 0.

3.

3. The preparation method according to claim 1, characterized in that, The reaction may or may not be carried out in a solvent; the solvent is selected from one or a mixture of two of toluene, ethylbenzene, and p-xylene.

4. The preparation method according to claim 1, characterized in that, The reaction may or may not be carried out in a solvent; the solvent is toluene.

5. The preparation method according to claim 1, characterized in that, The concentration ratio of the acetylacetic ester compound in the solvent is 0.03~0.2 g / mL.

6. The preparation method according to claim 5, characterized in that, The concentration ratio of the acetylacetic ester compounds in the solvent is 0.03~0.17 g / mL.

7. The preparation method according to claim 1, characterized in that, The reaction is carried out in a specific atmosphere, which is either an air atmosphere or a nitrogen atmosphere.

8. The preparation method according to claim 1, characterized in that, The reaction is carried out under heating conditions, and the heating temperature is 90~140℃.

9. The preparation method according to claim 1, characterized in that, The reaction time is 10-35 hours.

10. The preparation method according to claim 9, characterized in that, The reaction time is 12-32 hours.

11. The preparation method according to claim 1, characterized in that, After the reaction is completed, the mixture is cooled to room temperature and further separated and purified to obtain thiophene ester compounds.

12. The preparation method according to claim 11, characterized in that, The separation and purification process includes acid washing, vacuum distillation, and column chromatography separation.

13. The preparation method according to claim 12, characterized in that, The acid washing is performed by washing the reaction mixture with a dilute hydrochloric acid solution with a mass concentration of 8% to 15%, wherein the volume of the dilute hydrochloric acid solution is 1 to 3 times the volume of the reaction mixture.

14. The preparation method according to claim 12, characterized in that, The specific conditions for the vacuum distillation are: vacuum degree 22 torr, temperature 80°C. o C.

15. The preparation method according to claim 12, characterized in that, The eluent used in the column chromatography separation is: V(n-hexane):V(dichloromethane):V(methanol) = 60~80:15~25:5~15.

16. The preparation method according to claim 1, characterized in that, Compound 2 is selected from One or two of them.

17. The preparation method according to claim 1, characterized in that, When compound 2 is a mixture, it is further purified by reversed-phase column chromatography and then separated by preparative supercritical fluid chromatography.

18. A method for preparing thiophene ester compounds from levulinate ester compounds, comprising the following steps: Compound 1A, elemental sulfur reagent, aniline reagent and PTSA reagent were reacted. After the reaction mixture was cooled, it was separated by acid washing, vacuum distillation and column chromatography to obtain compound 2A and compound 2B. 。 19. The preparation method according to claim 18, characterized in that, Compound 1A was dissolved in a solvent at a concentration of 0.03–0.17 g / mL. Based on the molar ratio of compound 1A, elemental sulfur reagent (0.5–3), aniline reagent (0.5–1.5), and PTSA·H₂O reagent (0.01–0.3) were added. The mixture was then incubated at 90°C under a nitrogen atmosphere (1 bar) or an air atmosphere. o C~140 o React at C for 12 h to 32 h to obtain the reaction mixture.

20. The preparation method according to claim 18, characterized in that, After cooling, the reaction mixture was washed with a dilute hydrochloric acid solution of 8%–15% by mass, and then subjected to a vacuum of 22 torr and 80 torr. o Distillation under reduced pressure at C conditions, the residue was further separated by column chromatography to obtain a mixture of compounds 2A and 2B.

21. The preparation method according to claim 20, characterized in that, The mixture of compounds 2A and 2B was further purified by reverse-phase column chromatography and then separated by preparative supercritical fluid chromatography.

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