A method for synthesizing 2,5-dimethyl-3-furanethiol
By using 2,5-dimethyl-3-furanthiol as a raw material and employing ring-opening and ring-closing reactions, the problems of high cost and complexity in existing technologies have been solved, enabling low-cost, high-purity industrial production.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- JINAN ENLIGHTEN BIOTECH CO LTD
- Filing Date
- 2024-03-15
- Publication Date
- 2026-06-26
AI Technical Summary
The existing technology for synthesizing 2,5-dimethyl-3-furanthiol from 5-hydroxy-2-oxo-3-hexyne is costly and complex, making it difficult to apply to industrial production.
Using 2,5-dimethylfuran as a raw material, the reaction is carried out by heating with a ring-opening catalyst, followed by a temperature-controlled reaction with sublimed sulfur in deionized water, and then a ring-closing reaction with concentrated acid in an organic solvent to produce 2,5-dimethyl-3-furanthiol.
It reduces production costs, improves reaction selectivity and product purity, and is suitable for industrial production.
Smart Images
Figure CN118164934B_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of chemical organic synthesis technology, specifically to a method for synthesizing 2,5-dimethyl-3-furanthiol. Background Technology
[0002] The information disclosed in this background section is intended only to enhance understanding of the overall background of the invention and is not necessarily to be construed as an admission or in any way implying that such information constitutes prior art known to those skilled in the art.
[0003] Meat flavorings are a type of food flavoring, mainly including beef, pork, chicken, and lamb flavors. In various meat flavoring formulations, synthetic flavorings play a crucial role in improving the aroma intensity and realism of the flavorings, enhancing product characteristics, improving product quality, and reducing product costs. Among the many synthetic flavorings, furan flavorings are essential key flavorings in various high-end meat flavoring formulations. Furan sulfur compounds, in particular, have the strongest aroma characteristics and are the most important class of synthetic meat flavorings, as well as a variety that is being actively developed abroad.
[0004] 2,5-Dimethyl-3-furanthiol is a typical sulfur-containing furan flavoring compound with a good meaty aroma. When combined with other flavorings, it can produce a variety of natural food flavors and has high economic value.
[0005] US Patent 5470991 discloses the synthesis of 2,5-dimethyl-3-furanthiol from 5-hydroxy-2-oxo-3-hexyne. However, due to the high price of the raw material 5-hydroxy-2-oxo-3-hexyne, the cost of preparing 2,5-dimethyl-3-mercaptofuran is high. At the same time, the synthesis method of 2,5-dimethyl-3-furanthiol from 5-hydroxy-2-oxo-3-hexyne is complicated. Summary of the Invention
[0006] To overcome the above problems, this invention provides a method for synthesizing 2,5-dimethyl-3-furanthiol. This invention uses 2,5-dimethylfuran as a raw material and provides a method for synthesizing 2,5-dimethyl-3-furanthiol that is low-cost, involves few reaction steps, operates under mild reaction conditions, produces a high-purity product, and is suitable for industrial production.
[0007] To achieve the above technical objectives, the present invention adopts the following technical solution:
[0008] A method for synthesizing 2,5-dimethyl-3-furanthiol, comprising:
[0009] (1) After mixing 2,5-dimethylfuran with a ring-opening catalyst, the mixture was heated and reacted. After the reaction was completed, the crude intermediate 1 was obtained by extraction.
[0010] (2) Disperse crude intermediate 1 with sublimed sulfur in deionized water, heat to a specified temperature, introduce ammonia gas, and react under controlled temperature. After the reaction is completed, crude intermediate 2 is obtained.
[0011] (3) Disperse the crude intermediate 2 in deionized water, add concentrated acid while stirring, and then heat the reaction to obtain intermediate 3;
[0012] (4) Dissolve intermediate 3 in an organic solvent, then add a closed-ring catalyst, heat to reflux, reflux to separate water until no water is discharged, stop the reaction, and distill the reaction solution to obtain 2,5-dimethyl-3-furanthiol;
[0013] The reaction process is as follows:
[0014]
[0015] In one or more embodiments, in step (1), the ring-opening catalyst is a dilute acid solution, including one of dilute hydrochloric acid and dilute sulfuric acid;
[0016] Preferably, the concentration (mass fraction of solute) of the dilute acid is 20-30%.
[0017] In one or more embodiments, in step (1), the molar ratio of 2,5-dimethylfuran to the ring-opening catalyst is 1.3 to 1.6:1.
[0018] In one or more embodiments, in step (1), the temperature of the heating reaction is 80-85°C and the reaction time is 4-6 hours.
[0019] In one or more embodiments, in step (1), after the reaction is completed, sodium chloride is added to dissolve the reaction solution, dichloromethane is used to extract the reaction solution, and then dichloromethane is removed to obtain crude intermediate 1.
[0020] In one or more embodiments, in step (1), 2,5-dimethylfuran is mixed with a dilute acid solution and heated to 80-85°C for 4-6 hours. After the reaction is completed, sodium chloride is added to dissolve the reaction solution. The reaction solution is then extracted with dichloromethane and the dichloromethane is removed to obtain crude intermediate 1.
[0021] In one or more embodiments, in step (2), the mass ratio of sublimed sulfur to deionized water is 12 to 19:150.
[0022] In one or more embodiments, in step (2), the temperature is limited to 30-35°C.
[0023] In one or more embodiments, in step (2), the temperature of the temperature-controlled reaction is 30-40°C, and the reaction continues until the sulfur powder disappears.
[0024] In one or more embodiments, in step (2), after the reaction is completed, the ammonia gas is stopped and the reaction is continued at a constant temperature for 0.5 to 2 hours. The temperature of the reaction is the same as that of the temperature-controlled reaction. After the reaction is completed, the mixture is allowed to stand, the reaction liquid is separated into layers, the organic phase is collected, and it is washed with saturated brine to obtain crude intermediate 2.
[0025] In one or more embodiments, crude intermediate 1 and sublimed sulfur are dispersed in deionized water, heated to 30-35°C, and ammonia gas is introduced. The reaction is carried out at 30-40°C until the sulfur powder disappears. After the reaction is completed, the ammonia gas is stopped, and the reaction is continued at the same temperature for 0.5-2 hours. After the reaction is completed, the mixture is allowed to stand, the reaction liquid separates into layers, the organic phase is collected, and washed with saturated brine to obtain crude intermediate 2.
[0026] In one or more embodiments, in step (3), the concentrated acid includes either phosphoric acid or concentrated sulfuric acid.
[0027] In one or more embodiments, in step (3), the temperature of the heating reaction is 40 to 60°C, and the reaction time is 6 to 16 hours.
[0028] In one or more embodiments, in step (3), after the reaction is completed, the temperature is lowered to room temperature, the mixture is allowed to stand, the reaction liquid is separated into layers, the organic phase is collected and washed with water, and the washed organic phase is distilled to obtain intermediate 3.
[0029] In one or more embodiments, crude intermediate 2 is dispersed in deionized water, concentrated acid is added with stirring, and the reaction is carried out at 40-60°C for 6-16 hours. After the reaction is completed, the temperature is lowered to room temperature, and the mixture is allowed to stand. The reaction solution is separated into layers, the organic phase is collected, and the mixture is washed with water. The washed organic phase is then distilled to obtain intermediate 3.
[0030] In one or more embodiments, in step (4), the organic solvent is one or more of cyclohexane, benzene, toluene, chlorobenzene, o-dichlorobenzene, m-dichlorobenzene, p-dichlorobenzene, trichlorobenzene, mesitylene, o-chlorotoluene, m-chlorotoluene, p-chlorotoluene, o-xylene, m-xylene, p-xylene, trichlorobenzene, mesitylene, ethylbenzene, and propylbenzene, preferably toluene and cyclohexane.
[0031] In one or more embodiments, in step (4), the closed-loop catalyst comprises one of p-toluenesulfonic acid and concentrated sulfuric acid (98% by mass).
[0032] In one or more embodiments, in step (4), the molar ratio of intermediate 3 to the closed-ring catalyst is 1:0.15 to 0.2.
[0033] The beneficial effects of this invention are as follows:
[0034] (1) 2,5-Dimethyl-3-furanthiol is synthesized from 2,5-dimethylfuran. Direct thiolation of 2,5-dimethylfuran results in poor selectivity. In this invention, 2,5-dimethylfuran is first ring-opened to undergo thiol substitution, followed by ring closure to generate 2,5-dimethyl-3-furanthiol. To improve the selectivity of monothiol substitution, this invention employs a ring-closure and then ring-opening process for intermediate 1, avoiding the side reaction of dithiol substitution during direct thiol substitution of intermediate 1, thus improving the reaction selectivity.
[0035] (2) In this invention, intermediates 1 and 2 can be directly used in the next reaction, reducing the purification steps. Simultaneously, during the generation of intermediate 3 from intermediate 2, intermediate 1 can be recovered through distillation and reused in the reaction. The synthesis of 2,5-dimethyl-3-furanthiol from the purified intermediate 3 by distillation avoids side reactions, improves the yield and purity of 2,5-dimethyl-3-furanthiol, and the final separation of 2,5-dimethyl-3-furanthiol by distillation further enhances the purity of the product.
[0036] (3) The present invention uses 2,5-dimethylfuran, which is low in cost and readily available, as a raw material to produce 2,5-dimethyl-3-furanthiol. The entire production process has few reaction steps, mild reaction conditions, and high purity of the final product. Therefore, it is suitable for industrial production of 2,5-dimethyl-3-furanthiol. Attached Figure Description
[0037] The accompanying drawings, which form part of this invention, are used to provide a further understanding of the invention. The illustrative embodiments of the invention and their descriptions are used to explain the invention and do not constitute an improper limitation of the invention.
[0038] Figure 1 The gas phase spectrum of intermediate 1 in Example 1;
[0039] Figure 2 The gas phase spectrum of intermediate 2 in Example 1;
[0040] Figure 3 The gas phase spectrum of intermediate 3 in Example 1;
[0041] Figure 4 The image shows the gas phase spectrum of 2,5-dimethyl-3-furanthiol, the product from Example 1. Detailed Implementation
[0042] It should be noted that the following detailed descriptions are exemplary and intended to provide further illustration of the invention. Unless otherwise specified, all technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.
[0043] It should be noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the scope of exemplary embodiments according to the invention. As used herein, the singular form is intended to include the plural form as well, unless the context clearly indicates otherwise. Furthermore, it should be understood that when the terms "comprising" and / or "including" are used in this specification, they indicate the presence of features, steps, operations, devices, components, and / or combinations thereof.
[0044] To enable those skilled in the art to better understand the technical solution of the present invention, the technical solution of the present invention will be described in detail below with reference to specific embodiments.
[0045] Example 1
[0046] (1) Add 96g of 2,5-dimethylfuran and 200g of 25% hydrochloric acid to a 500mL reaction flask, heat to 82-84℃ and react for 5h. After the reaction is complete, cool to room temperature, add 30g of sodium chloride to dissolve the reaction solution, extract the reaction solution with dichloromethane (100mL×2), and then remove the dichloromethane by rotary evaporation to obtain crude intermediate 1. Crude intermediate 1 is directly used in the next step of the reaction. The gas phase spectrum of intermediate 1 is shown below. Figure 1 As shown.
[0047] (2) Add crude intermediate 1 and 16g of sublimed sulfur to a reaction flask containing 150mL of water, heat to 33℃, introduce ammonia gas, and react at a controlled temperature of 30-35℃ until the sulfur powder disappears. After the reaction is complete, stop introducing ammonia gas and continue the reaction at the same temperature as the controlled reaction. After the reaction is complete, let stand, the reaction liquid separates into layers, collect the organic phase, wash with saturated saline (50mL×2), and obtain 130g of crude intermediate 2. The gas phase spectrum of intermediate 2 is shown below. Figure 2 As shown.
[0048] (3) Crude intermediate 2 was added to a reaction flask, followed by 300 mL of deionized water. 85 g of phosphoric acid was added while stirring. The reaction was maintained at 55–60 °C for 8 h. After the reaction was complete, the mixture was cooled to room temperature and allowed to stand. The reaction solution separated into layers. The organic phase was collected and washed with water (100 mL × 2). The washed organic phase was then distilled to obtain 60 g of intermediate 3 with a purity of 98%, yielding 41% based on 2,5-dimethylfuran. Additionally, 45 g of intermediate 1 was recovered by distillation. The gas phase spectrum of intermediate 3 is shown below. Figure 3 As shown.
[0049] (4) Add 60g of intermediate 3 to 200mL of cyclohexane, then add 5g of p-toluenesulfonic acid, heat to reflux, and separate the water under reflux until no water is discharged. Stop the reaction, and distill the reaction mixture to obtain 35g of 2,5-dimethyl-3-furanthiol. The content was determined to be 99.5%, and the yield was 66%. The gas chromatogram of the product 2,5-dimethyl-3-furanthiol is shown below. Figure 4 As shown.
[0050] Example 2
[0051] (1) Add 96g of 2,5-dimethylfuran and 200g of 20% dilute sulfuric acid to a 500mL reaction flask, heat to 83-85℃ and react for 5h. After the reaction is complete, cool to room temperature, add 30g of sodium chloride to dissolve the reaction solution, extract the reaction solution with dichloromethane (100mL×2), and then remove the dichloromethane by rotary evaporation to obtain crude intermediate 1. Crude intermediate 1 is directly used in the next step of the reaction.
[0052] (2) Add the crude intermediate 1 and 18g of sublimed sulfur to a reaction flask containing 150mL of water, heat to 33℃, introduce ammonia gas, and react at 35-40℃ until the sulfur powder disappears. After the reaction is completed, stop the ammonia gas and continue to keep the temperature for 1h. The temperature of the heat preservation reaction is the same as that of the temperature control reaction. After the heat preservation reaction is completed, let stand, the reaction liquid separates into layers, collect the organic phase, wash with saturated saline (50mL×2), and obtain 128g of crude intermediate 2.
[0053] (3) Crude intermediate 2 was added to a reaction flask, followed by 300 mL of deionized water. 85 g of concentrated sulfuric acid was added while stirring. The reaction was carried out at 40–45 °C for 15 h. After the reaction was complete, the mixture was cooled to room temperature and allowed to stand. The reaction solution separated into layers. The organic phase was collected and washed with water (100 mL × 2). The washed organic phase was then distilled to obtain 63 g of intermediate 3 with a purity of 97%, yielding 43% based on 2,5-dimethylfuran. Additionally, 41 g of intermediate 1 was recovered by distillation.
[0054] (4) Add 63g of intermediate 3 to 200mL of toluene, then add 5g of concentrated sulfuric acid (98% by mass), heat to reflux, reflux to separate water until no water is discharged, stop the reaction, distill the reaction liquid to obtain 38g of 2,5-dimethyl-3-furanthiol, the content of which is 99.5% and the yield is 69%.
[0055] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.
Claims
1. A method for synthesizing 2,5-dimethyl-3-furanthiol, characterized in that, include: (1) After mixing 2,5-dimethylfuran with a ring-opening catalyst, the mixture was heated and reacted. After the reaction was completed, the crude intermediate 1 was obtained by extraction. (2) Disperse crude intermediate 1 and sublimed sulfur in deionized water, heat to a specified temperature, introduce ammonia gas, and react under controlled temperature. After the reaction is completed, crude intermediate 2 is obtained. (3) Disperse the crude intermediate 2 in deionized water, stir and add concentrated acid, and then heat to react to obtain intermediate 3; (4) Dissolve intermediate 3 in an organic solvent, then add a closed-ring catalyst, heat to reflux, reflux to separate water until no water is discharged, stop the reaction, and distill the reaction solution to obtain 2,5-dimethyl-3-furanthiol; The reaction process is as follows: ； In step (1), the ring-opening catalyst is a dilute acid solution, selected from dilute hydrochloric acid and dilute sulfuric acid; In step (3), the concentrated acid is selected from either phosphoric acid or concentrated sulfuric acid; In step (4), the closed-ring catalyst is selected from p-toluenesulfonic acid and concentrated sulfuric acid.
2. The method for synthesizing 2,5-dimethyl-3-furanthiol as described in claim 1, characterized in that, The concentration of the dilute acid is 20-30%.
3. The method for synthesizing 2,5-dimethyl-3-furanthiol as described in claim 1, characterized in that, In step (1), the temperature of the heating reaction is 80~85 ℃, and the reaction time is 4~6 h; Alternatively, in step (1), after the reaction is complete, sodium chloride is added to dissolve the reaction solution, dichloromethane is used to extract the reaction solution, and then dichloromethane is removed to obtain crude intermediate 1.
4. The method for synthesizing 2,5-dimethyl-3-furanthiol as described in claim 1, characterized in that, In step (2), the mass ratio of sublimed sulfur to deionized water is 12~19:150; Alternatively, in step (2), the temperature is limited to 30~35 ℃.
5. The method for synthesizing 2,5-dimethyl-3-furanthiol as described in claim 1, characterized in that, In step (2), the temperature of the controlled reaction is 30~40 ℃, and the reaction continues until the sulfur powder disappears; Alternatively, in step (2), after the reaction is completed, stop the ammonia gas supply and continue the reaction at a constant temperature for 0.5 to 2 hours. The temperature of the reaction at a constant temperature is the same as that of the temperature-controlled reaction. After the reaction is completed, let it stand, the reaction liquid separates into layers, collect the organic phase, wash it with saturated brine, and obtain crude intermediate 2.
6. The method for synthesizing 2,5-dimethyl-3-furanthiol as described in claim 1, characterized in that, In step (3), the temperature of the heating reaction is 40~60℃ and the reaction time is 6~16 h.
7. The method for synthesizing 2,5-dimethyl-3-furanthiol as described in claim 1, characterized in that, In step (3), after the reaction is completed, the temperature is lowered to room temperature, and the reaction solution is allowed to stand. The reaction solution is separated into layers, the organic phase is collected, and it is washed with water. The washed organic phase is then distilled to obtain intermediate 3.
8. The method for synthesizing 2,5-dimethyl-3-furanthiol as described in claim 1, characterized in that, In step (4), the organic solvent is one or more of cyclohexane, benzene, toluene, chlorobenzene, o-dichlorobenzene, m-dichlorobenzene, p-dichlorobenzene, trichlorobenzene, mesitylene, o-chlorotoluene, m-chlorotoluene, p-chlorotoluene, o-xylene, m-xylene, p-xylene, trichlorobenzene, mesitylene, ethylbenzene, and propylbenzene.
9. The method for synthesizing 2,5-dimethyl-3-furanthiol as described in claim 8, characterized in that, The organic solvents are toluene and cyclohexane.
10. The method for synthesizing 2,5-dimethyl-3-furanthiol according to claim 1, characterized in that, In step (4), the molar ratio of intermediate 3 to the closed-ring catalyst is 1:0.15~0.2.