A method for preparing ethyl acetate solution of 2-furanmethylthioic acid

Abstract

The invention discloses a method for preparing an ethyl acetate solution of 2-furan methylthioic acid, which belongs to the technical field of drug synthesis, including a) simultaneously pumping a sodium sulfide aqueous solution, ethyl acetate, 2-furan methylthioyl chloride, phosphoric acid, a catalyst, and deionized water into a tubular reactor I to generate a 2-furan methylthioic acid sodium ethyl acetate solution; b) simultaneously pumping the 2-furan methylthioic acid sodium ethyl acetate solution, ethyl acetate, and hydrochloric acid into a tubular reactor II to generate a mixed solution of 2-furan methylthioic acid ethyl acetate solution and water; c) pumping the mixed solution into a rotary disc extraction tower, separating the ethyl acetate phase and the aqueous phase to obtain the 2-furan methylthioic acid ethyl acetate solution, and the beneficial effects of the invention are: achieving the effect of continuous feeding and continuous discharging; using trans-cyclohexylene diamine as a catalyst to accelerate the reaction rate, improve the reaction yield, reduce the unit consumption of raw materials, and reduce the occupation of the production site. The invention has high production efficiency and is suitable for industrial production.

Description

Technical field:

[0001] The invention belongs to the technical field of drug synthesis, and more specifically relates to a method for preparing an ethyl acetate solution of 2-furothioic acid. Background technology:

[0002] Ceftiofur sodium is a third-generation cephalosporin antibiotic used exclusively in veterinary medicine. It exhibits broad-spectrum, highly effective bactericidal activity against both Gram-positive and Gram-negative bacteria, including β-lactamase-producing strains. It is rapidly absorbed after intramuscular and subcutaneous injection, reaching peak effective blood concentrations in 0.5-0.3 hours. It exhibits widespread distribution throughout the body, making it a promising new drug for the clinical treatment of bacterial diseases. Market research indicates that many of the top 100 veterinary chemical companies in China offer ceftiofur sodium. Furthermore, as a new generation cephalosporin antibiotic, ceftiofur sodium is one of the most widely used antibiotics in livestock production. Recently, the price of ceftiofur sodium has been rising, indicating high market demand and promising market prospects.

[0003] Various production methods are currently available for 2-furothioic acid, an important intermediate of ceftiofur sodium. For example, Chinese patent publication CN221714271U discloses a synthesis apparatus for 7-ACF, a ceftiofur intermediate. This method uses ethyl acetate as a solvent, 2-furoyl chloride as a starting material, and sodium hydrosulfide to produce 2-furothioic acid under certain conditions. However, this method employs a batch-type tank reactor, resulting in high raw material consumption, multiple equipment, a large production footprint, a long production cycle, and low efficiency. Summary of the invention:

[0004] To solve the above problems and overcome the shortcomings of the existing technology, the present invention provides a method for preparing an ethyl acetate solution of 2-furomethylthioic acid using a tubular reactor, which can effectively solve the disadvantages of the intermittent mode of a tank reactor, such as high raw material consumption, multiple equipment, large production area, long production cycle, and low efficiency.

[0005] The specific technical solution of the present invention to solve the above technical problems is: a method for preparing sodium 2-furothioate ethyl acetate solution, characterized by comprising the following steps:

[0006] a) simultaneously pumping a sodium sulfide aqueous solution, ethyl acetate, 2-furoyl chloride, phosphoric acid, and deionized water into a tubular reactor I to generate an ethyl acetate solution of sodium 2-furoylthioate;

[0007] b) simultaneously pumping the sodium 2-furylthioate ethyl acetate solution, ethyl acetate, and hydrochloric acid into a tubular reactor II to generate a mixture of the sodium 2-furylthioate ethyl acetate solution and water;

[0008] c) pumping the mixed solution into a rotary disc extraction tower to separate the ethyl acetate phase and the aqueous phase to obtain an ethyl acetate solution of 2-furothioic acid.

[0009] Furthermore, in step a), a catalyst trans-cyclohexanediamine is added.

[0010] a) simultaneously pumping a sodium sulfide aqueous solution, ethyl acetate, 2-furoyl chloride, phosphoric acid, deionized water, and trans-cyclohexanediamine into a tubular reactor I to generate an ethyl acetate solution of sodium 2-furoylthioate;

[0011] Furthermore, in step a), the concentration of the sodium sulfide aqueous solution is 10% to 40%,

[0012] Furthermore, the mass flow ratio of the sodium sulfide aqueous solution, ethyl acetate, 2-furoyl chloride, phosphoric acid, water, and trans-cyclohexanediamine is 1:0.37:0.59:0.05:2.4:0.02.

[0013] Furthermore, the reaction temperature in step a) is 10°C to 20°C.

[0014] Furthermore, in step b), when the mass flow ratio of sodium hydrosulfide aqueous solution, ethyl acetate, 2-furoyl chloride, phosphoric acid, and water is 1:0.37:0.59:0.05:2.4, the mass flow ratio of ethyl acetate reaction solution, ethyl acetate, and hydrochloric acid is 1:0.125:0.1.

[0015] The beneficial effects of the present invention are:

[0016] The present invention uses a tubular reactor as a reaction container, and pumps the reaction raw materials into the reactor through a tetrafluoroethylene constant flow pump. The reactor has good mass and heat transfer effects, so the reaction temperature can be better controlled, thereby accelerating the speed of dropping the sodium sulfide aqueous solution and 2-furoyl chloride, and achieving the effects of continuous feeding and continuous discharging.

[0017] The invention accelerates the reaction rate by adding trans-cyclohexanediamine as a catalyst, improves the reaction yield, reduces the unit consumption of raw materials, and reduces the occupation of production space. The invention has high production efficiency and is suitable for industrial production. Description of the drawings:

[0018] Attachment Figure 1 It is a process flow chart of the present invention;

[0019] Attachment Figure 2 This is a liquid chromatography detection diagram of 2-furoyl chloride in an embodiment of the present invention; Specific implementation method:

[0020] In the description of the present invention, specific details are provided solely to facilitate a thorough understanding of the embodiments of the present invention. However, those skilled in the art will appreciate that the present invention is not limited to these details. Furthermore, well-known structures and functions have not been described or illustrated in detail to avoid obscuring the key points of the embodiments of the present invention. Those skilled in the art will appreciate the specific meanings of the above terms as used in the present invention.

[0021] Specific implementation of the present invention:

[0022] In order to better understand the present invention, a specific embodiment is used for illustration. It is worth emphasizing that the effects of this embodiment are not substantially different from those of various embodiments within the scope of protection of the present invention, including the respective reagents and the content ratios of the reagents. All of them can achieve the effects described in the present invention and solve the above-mentioned problems. Other combinations are not described here.

[0023] Example 1

[0024] A 20°C refrigerant was introduced into the tubular reactor I. After the temperature stabilized, a tetrafluoroethylene constant flow pump was started to pump a 21% sodium sulfide aqueous solution into the tubular reactor I at a rate of 4.33 g / min, 2-furoyl chloride was pumped into the tubular reactor I at a rate of 1.6 g / min, ethyl acetate was pumped into the tubular reactor I at a rate of 2.25 g / min, phosphoric acid was pumped into the tubular reactor I at a rate of 0.23 g / min, and deionized water was pumped into the tubular reactor I at a rate of 14.1 g / min. After continuous introduction for 3 hours, the 2-furoyl chloride content was detected by the central control to be ≤0.2%, thereby obtaining an ethyl acetate solution of sodium 2-furothioate;

[0025] After completing the above steps, the ethyl acetate solution of sodium 2-furothioate was pumped into the tubular reactor II at a rate of 22.56 g / min, ethyl acetate was pumped in at a rate of 2.81 g / min, and hydrochloric acid was pumped in at a rate of 2.35 g / min. The pumping was continued simultaneously for 20 minutes, at which time the reactor began to discharge the material to obtain a mixture of the ethyl acetate solution of 2-furothioate and water;

[0026] The obtained mixture of 2-furylthioic acid ethyl acetate solution and water was pumped into the lower feed section of the rotary disc extraction tower at a rate of 27.72 g / min. The extraction tower was started for stirring. After the feed liquid filled the extraction tower and the materials in the upper and lower clarification sections were clarified, the aqueous phase and the ethyl acetate phase were separated to obtain the 2-furylthioic acid ethyl acetate solution;

[0027] The content of 2-furomethylthioic acid in the obtained ethyl acetate solution of 2-furomethylthioic acid was determined to be 16.75%, and the yield was 97.5%.

[0028] Example 2

[0029] A 10°C refrigerant was introduced into the tubular reactor I. After the temperature stabilized, a tetrafluoroethylene constant flow pump was started to pump a 21% sodium sulfide aqueous solution into the tubular reactor I at a rate of 4.33 g / min, 2-furoyl chloride was pumped into the tubular reactor I at a rate of 1.6 g / min, ethyl acetate was pumped into the tubular reactor I at a rate of 2.25 g / min, phosphoric acid was pumped into the tubular reactor I at a rate of 0.23 g / min, and deionized water was pumped into the tubular reactor I at a rate of 14.1 g / min. After continuous introduction for 3 hours, the 2-furoyl chloride content was detected by the central control to be ≤0.2%, thereby obtaining an ethyl acetate solution of sodium 2-furothioate;

[0030] After completing the above steps, the ethyl acetate solution of sodium 2-furothioate was pumped into the tubular reactor II at a rate of 22.56 g / min, ethyl acetate was pumped in at a rate of 2.81 g / min, and hydrochloric acid was pumped in at a rate of 2.35 g / min. The pumping was continued simultaneously for 20 minutes, at which time the reactor began to discharge the material to obtain a mixture of the ethyl acetate solution of 2-furothioate and water;

[0031] The obtained mixture of 2-furylthioic acid ethyl acetate solution and water was pumped into the lower feed section of the rotary disc extraction tower at a rate of 27.72 g / min. The extraction tower was started for stirring. After the feed liquid filled the extraction tower and the materials in the upper and lower clarification sections were clarified, the aqueous phase and the ethyl acetate phase were separated to obtain the 2-furylthioic acid ethyl acetate solution;

[0032] The content of 2-furomethylthioic acid in the obtained ethyl acetate solution of 2-furomethylthioic acid was determined to be 16.82%, and the yield was 97.9%.

[0033] Example 3

[0034] A 14°C refrigerant was introduced into the tubular reactor I. After the temperature stabilized, a tetrafluoroethylene constant flow pump was started to pump a 21% sodium sulfide aqueous solution into the tubular reactor I at a rate of 4.33 g / min, 2-furoyl chloride was pumped into the tubular reactor I at a rate of 1.6 g / min, ethyl acetate was pumped into the tubular reactor I at a rate of 2.25 g / min, phosphoric acid was pumped into the tubular reactor I at a rate of 0.23 g / min, and deionized water was pumped into the tubular reactor I at a rate of 14.1 g / min. After continuous introduction for 3 hours, the 2-furoyl chloride content was detected by the central control to be ≤0.2%, thereby obtaining an ethyl acetate solution of sodium 2-furothioate;

[0035] After completing the above steps, the ethyl acetate solution of sodium 2-furothioate was pumped into the tubular reactor II at a rate of 22.56 g / min, ethyl acetate was pumped in at a rate of 2.81 g / min, and hydrochloric acid was pumped in at a rate of 2.35 g / min. The pumping was continued simultaneously for 20 minutes, at which time the reactor began to discharge the material to obtain a mixture of the ethyl acetate solution of 2-furothioate and water;

[0036] The obtained mixture of 2-furylthioic acid ethyl acetate solution and water was pumped into the lower feed section of the rotary disc extraction tower at a rate of 27.72 g / min. The extraction tower was started for stirring. After the feed liquid filled the extraction tower and the materials in the upper and lower clarification sections were clarified, the aqueous phase and the ethyl acetate phase were separated to obtain the 2-furylthioic acid ethyl acetate solution;

[0037] The content of 2-furomethylthioic acid in the obtained ethyl acetate solution of 2-furomethylthioic acid was determined to be 16.72%, and the yield was 97.3%.

[0038] In order to more intuitively demonstrate the process advantages of the present invention, the equivalent replacement method is used for comparison.

[0039] Comparative Example 1:

[0040] The preparation method is the same as that in the embodiment, except that: in the preparation process of this comparative example, a batch reaction in a tank reactor is adopted, specifically:

[0041] Add 22.5 g of ethyl acetate, 140.6 g of deionized water, and 2.3 g of phosphoric acid to the reaction flask, cool to 10°C, and dropwise add 43.3 g of a 21% aqueous sodium sulfide solution and 16 g of 2-furoyl chloride. Control the addition temperature at 20-30°C for 2 hours and keep warm for 3 hours. If the 2-furoyl chloride content is ≤0.2% when detected by the central control, the reaction is qualified to obtain a mixed solution of sodium 2-furothioate with ethyl acetate and water;

[0042] To the obtained mixed solution of sodium 2-furothioate in ethyl acetate and water, 28 g of ethyl acetate was added, and 23.5 g of 37% hydrochloric acid was slowly added dropwise. After the addition was completed, stirring was performed for 1 hour to obtain a mixed solution of sodium 2-furothioate in ethyl acetate and water;

[0043] The obtained mixed solution of ethyl 2-furothioate and water was transferred to a separatory funnel, allowed to stand for separation, and the aqueous layer was discarded to obtain an ethyl 2-furothioate solution;

[0044] The content of 2-furomethylthioic acid in the obtained ethyl acetate solution of 2-furomethylthioic acid was determined to be 16.1%, and the yield was 93.7%.

[0045] Comparative Example 2:

[0046] The preparation method is the same as that of the embodiment, except that: in the preparation process of this comparative example, the refrigerant reaction temperature is different, which is 5°C;

[0047] A 5°C refrigerant was introduced into the tubular reactor I. After the temperature stabilized, a tetrafluoroethylene constant flow pump was started to pump a 21% sodium sulfide aqueous solution into the tubular reactor I at a rate of 4.33 g / min, 2-furoyl chloride was pumped at a rate of 1.6 g / min, ethyl acetate was pumped at a rate of 2.25 g / min, phosphoric acid was pumped at a rate of 0.23 g / min, and deionized water was pumped at a rate of 14.1 g / min. After continuous introduction for 3 hours, the central control detected that the 2-furoyl chloride content was ≤0.2%, the reaction was qualified, and an ethyl acetate solution of sodium 2-furothioate was obtained;

[0048] After completing the above steps, the ethyl acetate solution of sodium 2-furothioate was pumped into the tubular reactor II at a rate of 22.51 g / min, ethyl acetate was pumped in at a rate of 2.81 g / min, and hydrochloric acid was pumped in at a rate of 2.35 g / min. The pumping was continued simultaneously for 20 minutes, at which time the reactor began to discharge the material to obtain a mixture of the ethyl acetate solution of 2-furothioate and water;

[0049] The obtained mixture of 2-furylthioic acid ethyl acetate solution and water was pumped into the lower feed section of the rotary disc extraction tower at a rate of 27.67 g / min. The extraction tower was started for stirring. After the feed liquid filled the extraction tower and the materials in the upper and lower clarification sections were clarified, the aqueous phase and the ethyl acetate phase were separated to obtain the 2-furylthioic acid ethyl acetate solution;

[0050] The content of 2-furomethylthioic acid in the obtained ethyl acetate solution of 2-furomethylthioic acid was determined to be 16.12%, and the converted yield was 93.83%.

[0051] Comparative Example 3:

[0052] The preparation method is the same as that of the embodiment, except that: in the preparation process of this comparative example, the heat medium reaction temperature is different and is 45°C;

[0053] A 45°C heat medium was introduced into the tubular reactor I. After the temperature stabilized, a tetrafluoroethylene constant flow pump was started to pump a 21% sodium sulfide aqueous solution into the tubular reactor I at a rate of 4.33 g / min, 2-furoyl chloride was pumped at a rate of 1.6 g / min, ethyl acetate was pumped at a rate of 2.25 g / min, phosphoric acid was pumped at a rate of 0.23 g / min, and deionized water was pumped at a rate of 14.1 g / min. After continuous introduction for 3 hours, the central control detected that the 2-furoyl chloride content was ≤0.2%, the reaction was qualified, and an ethyl acetate solution of sodium 2-furothioate was obtained;

[0054] After completing the above steps, the ethyl acetate solution of sodium 2-furothioate was pumped into the tubular reactor II at a rate of 22.51 g / min, ethyl acetate was pumped in at a rate of 2.81 g / min, and hydrochloric acid was pumped in at a rate of 2.35 g / min. The pumping was continued simultaneously for 20 minutes, at which time the reactor began to discharge the material to obtain a mixture of the ethyl acetate solution of 2-furothioate and water;

[0055] The obtained mixture of 2-furylthioic acid ethyl acetate solution and water was pumped into the lower feed section of the rotary disc extraction tower at a rate of 27.67 g / min. The extraction tower was started for stirring. After the feed liquid filled the extraction tower and the materials in the upper and lower clarification sections were clarified, the aqueous phase and the ethyl acetate phase were separated to obtain the 2-furylthioic acid ethyl acetate solution;

[0056] The content of 2-furomethylthioic acid in the obtained ethyl acetate solution of 2-furomethylthioic acid was determined to be 16.1%, and the yield was 93.71%.

[0057] Table 1: Comparison of the indexes and yields of 2-furanmethylthioic acid obtained in the examples and comparative examples

[0058]

[0059] As can be seen from Table 1,

[0060] (1) The 2-furothioic acid solution obtained by the production method provided by the present invention has a high content, and the yield is increased by about 3.99%, thereby realizing continuous production and greatly improving production efficiency.

[0061] (2) Comparative Example 1: The difference is that the batch reaction using a tank reactor has a lower yield and content than the present invention, and can only be operated batchwise.

[0062] (3) Comparative Example 2: The refrigerant reaction temperature is 5°C; Comparative Example 3: The hot medium reaction temperature is 45°C; the yield and content are both lower than those of the present invention. It can be seen that the reaction temperature in step a), i.e., the refrigerant reaction temperature is 10°C to 20°C, has a relatively positive effect on the content of 2-furothioic acid in the ethyl acetate solution and the total yield.

[0063] In particular, the tubular reactor is used as a reaction vessel, and the reaction raw materials are pumped into the reactor through a tetrafluoroethylene constant flow pump. The reactor has good mass transfer and heat transfer effects, which can better control the reaction temperature, thereby accelerating the speed of adding sodium sulfide aqueous solution and 2-furoyl chloride, and achieving the effect of continuous feeding and continuous discharging.

[0064] In order to more intuitively demonstrate the process advantages of the present invention, the present invention also investigates the effect of the catalyst trans-cyclohexanediamine on the reaction.

[0065] Example 4

[0066] A 14°C refrigerant was introduced into the tubular reactor I. After the temperature stabilized, a tetrafluoroethylene constant flow pump was started to pump a 21% sodium sulfide aqueous solution into the tubular reactor I at a rate of 4.33 g / min, 2-furoyl chloride was pumped into the tubular reactor I at a rate of 1.6 g / min, ethyl acetate was pumped into the tubular reactor I at a rate of 2.25 g / min, phosphoric acid was pumped into the tubular reactor I at a rate of 0.23 g / min, deionized water was pumped into the tubular reactor I at a rate of 14.1 g / min, and trans-cyclohexanediamine was pumped into the tubular reactor I at a rate of 0.05 g / min. After continuous introduction for 1 hour, the central control detected that the 2-furoyl chloride content was ≤0.2%, the reaction was qualified, and an ethyl acetate solution of sodium 2-furothioate was obtained;

[0067] After completing the above steps, the ethyl acetate solution of sodium 2-furothioate was pumped into the tubular reactor II at a rate of 22.51 g / min, ethyl acetate was pumped in at a rate of 2.81 g / min, and hydrochloric acid was pumped in at a rate of 2.35 g / min. The pumping was continued simultaneously for 20 minutes, at which time the reactor began to discharge the material to obtain a mixture of the ethyl acetate solution of 2-furothioate and water;

[0068] The mixture of the obtained 2-furylthioic acid ethyl acetate solution and water was pumped into the lower feed section of the rotary extraction tower at a rate of 27.67 g / min, and the extraction tower was started to stir. After the feed liquid filled the extraction tower and the materials in the upper and lower clarification sections were clarified, the aqueous phase and the ethyl acetate phase were separated to obtain 2-furylthioic acid ethyl acetate solution.

[0069] The content of 2-furomethylthioic acid in the obtained ethyl acetate solution of 2-furomethylthioic acid was determined to be 16.75%, and the yield was 97.5%.

[0070] Example 5

[0071] A 14°C refrigerant was introduced into the tubular reactor I. After the temperature stabilized, a tetrafluoroethylene constant flow pump was started to pump a 21% sodium sulfide aqueous solution into the tubular reactor I at a rate of 4.33 g / min, 2-furoyl chloride was pumped into the tubular reactor I at a rate of 1.6 g / min, ethyl acetate was pumped into the tubular reactor I at a rate of 2.25 g / min, phosphoric acid was pumped into the tubular reactor I at a rate of 0.23 g / min, deionized water was pumped into the tubular reactor I at a rate of 14.1 g / min, and trans-cyclohexanediamine was pumped into the tubular reactor I at a rate of 0.1 g / min. After continuous introduction for 1 hour, the central control detected that the 2-furoyl chloride content was ≤0.2%, the reaction was qualified, and an ethyl acetate solution of sodium 2-furothioate was obtained;

[0072] After completing the above steps, the ethyl acetate solution of sodium 2-furothioate was pumped into the tubular reactor II at a rate of 22.51 g / min, ethyl acetate was pumped in at a rate of 2.81 g / min, and hydrochloric acid was pumped in at a rate of 2.35 g / min. The pumping was continued simultaneously for 20 minutes, at which time the reactor began to discharge the material to obtain a mixture of the ethyl acetate solution of 2-furothioate and water;

[0073] The mixture of the obtained 2-furylthioic acid ethyl acetate solution and water was pumped into the lower feed section of the rotary extraction tower at a rate of 27.67 g / min, and the extraction tower was started to stir. After the feed liquid filled the extraction tower and the materials in the upper and lower clarification sections were clarified, the aqueous phase and the ethyl acetate phase were separated to obtain 2-furylthioic acid ethyl acetate solution.

[0074] The content of 2-furomethylthioic acid in the obtained ethyl acetate solution of 2-furomethylthioic acid was determined to be 16.82%, and the yield was 97.90%.

[0075] Example 6

[0076] A 14°C refrigerant was introduced into the tubular reactor I. After the temperature stabilized, a tetrafluoroethylene constant flow pump was started to pump a 21% sodium sulfide aqueous solution into the tubular reactor I at a rate of 4.33 g / min, 2-furoyl chloride was pumped into the tubular reactor I at a rate of 1.6 g / min, ethyl acetate was pumped into the tubular reactor I at a rate of 2.25 g / min, phosphoric acid was pumped into the tubular reactor I at a rate of 0.23 g / min, deionized water was pumped into the tubular reactor I at a rate of 14.1 g / min, and trans-cyclohexanediamine was pumped into the tubular reactor I at a rate of 0.15 g / min. After continuous introduction for 1 hour, the central control detected that the 2-furoyl chloride content was ≤0.2%, the reaction was qualified, and an ethyl acetate solution of sodium 2-furothioate was obtained;

[0077] After completing the above steps, the ethyl acetate solution of sodium 2-furothioate was pumped into the tubular reactor II at a rate of 22.51 g / min, ethyl acetate was pumped in at a rate of 2.81 g / min, and hydrochloric acid was pumped in at a rate of 2.35 g / min. The pumping was continued simultaneously for 20 minutes, at which time the reactor began to discharge the material to obtain a mixture of the ethyl acetate solution of 2-furothioate and water;

[0078] The mixture of the obtained 2-furylthioic acid ethyl acetate solution and water was pumped into the lower feed section of the rotary extraction tower at a rate of 27.67 g / min, and the extraction tower was started to stir. After the feed liquid filled the extraction tower and the materials in the upper and lower clarification sections were clarified, the aqueous phase and the ethyl acetate phase were separated to obtain 2-furylthioic acid ethyl acetate solution.

[0079] The content of 2-furomethylthioic acid in the obtained ethyl acetate solution of 2-furomethylthioic acid was determined to be 16.72%, and the yield was 97.30%.

[0080] Comparative Example 4:

[0081] The preparation method is the same as that of Example 3, except that in the preparation process of this comparative example, the catalyst is replaced with cyclopentanediamine;

[0082] A 14°C refrigerant was introduced into the tubular reactor I. After the temperature stabilized, a tetrafluoroethylene constant flow pump was started to pump a 21% sodium sulfide aqueous solution into the tubular reactor I at a rate of 4.33 g / min, 2-furoyl chloride was pumped into the tubular reactor I at a rate of 1.6 g / min, ethyl acetate was pumped into the tubular reactor I at a rate of 2.25 g / min, phosphoric acid was pumped into the tubular reactor I at a rate of 0.23 g / min, deionized water was pumped into the tubular reactor I at a rate of 14.1 g / min, and cyclopentanediamine was pumped into the tubular reactor I at a rate of 0.1 g / min. After continuous introduction for 3 hours, the central control detected that the 2-furoyl chloride content was ≤0.2%, the reaction was qualified, and an ethyl acetate solution of sodium 2-furothioate was obtained;

[0083] After completing the above steps, the ethyl acetate solution of sodium 2-furothioate was pumped into the tubular reactor II at a rate of 22.51 g / min, ethyl acetate was pumped in at a rate of 2.81 g / min, and hydrochloric acid was pumped in at a rate of 2.35 g / min. The pumping was continued simultaneously for 20 minutes, at which time the reactor began to discharge the material to obtain a mixture of the ethyl acetate solution of 2-furothioate and water;

[0084] The obtained mixture of 2-furylthioic acid ethyl acetate solution and water was pumped into the lower feed section of the rotary disc extraction tower at a rate of 27.67 g / min. The extraction tower was started for stirring. After the feed liquid filled the extraction tower and the materials in the upper and lower clarification sections were clarified, the aqueous phase and the ethyl acetate phase were separated to obtain the 2-furylthioic acid ethyl acetate solution;

[0085] The content of 2-furomethylthioic acid in the obtained ethyl acetate solution of 2-furomethylthioic acid was determined to be 16.78%, and the yield was 97.67%.

[0086] The control detection method in the above embodiment and comparative example:

[0087] 1. Instruments and Equipment

[0088] High performance liquid chromatography, 100,000th balance

[0089] 2. Reagent solution

[0090] 2-Furoyl chloride reference substance, methanol, 0.01 mol / L ammonium acetate solution.

[0091] 3. Chromatographic conditions

[0092] Column type: C18 (4.6mm×250mm×5μm) or similar type column

[0093] Mobile phase: 0.01 mol / L ammonium acetate solution: methanol = 55:45

[0094] Detector: UV = 254 nm

[0095] Flow rate: 1.0 mL / min

[0096] Column temperature: 25°C

[0097] Injection volume: 20 μL

[0098] Run time: 25 minutes

[0099] 4. Assay

[0100] Weigh 15 mg of sample (accurate to 0.0001 g) into a 100 mL volumetric flask, dissolve it with mobile phase, and dilute to the mark. Shake well to prepare the test solution. Inject the test solution into the HPLC system for detection.

[0101] 5. Calculation method

[0102] According to the area normalization method, calculate the purity of 2-furoyl chloride in the test sample, which should be ≤0.2%.

[0103] Table 2: Indices, yields and reaction times of 2-furothioic acid obtained in Examples and Comparative Examples

[0104]

[0105]

[0106] As can be seen from Table 2,

[0107] (1) Compared with Examples 1-3 of the present invention, the 2-furanmethylthioic acid solution obtained by the process provided in Examples 4-6 of the present invention has a higher content, which is further improved, the yield is increased by about 3.99%, and the reaction time is reduced from 3 hours to 1 hour, thereby realizing continuous production and greatly improving production efficiency.

[0108] (2) Comparative Example 4: The difference is that the catalyst is replaced with cyclopentanediamine;

[0109] Although the catalyst cyclopentanediamine was added to Comparative Example 4, cyclopentanediamine, as a homologue of trans-cyclohexanediamine, did not increase the content of 2-furothioic acid solution, especially the reaction time was no different from that of Comparative Examples 1-3.

[0110] In summary:

[0111] The present invention uses a tubular reactor as a reaction container, and pumps the reaction raw materials into the reactor through a tetrafluoroethylene constant flow pump. The reactor has good mass and heat transfer effects, so the reaction temperature can be better controlled, thereby accelerating the speed of dropping the sodium sulfide aqueous solution and 2-furoyl chloride, and achieving the effects of continuous feeding and continuous discharging.

[0112] The invention accelerates the reaction rate by adding trans-cyclohexanediamine as a catalyst, improves the reaction yield, reduces the unit consumption of raw materials, and reduces the occupation of production space. The invention has high production efficiency and is suitable for industrial production.

Claims

1. A method for preparing sodium 2-furanthioate ethyl acetate solution, characterized in that The following steps are involved: (a) simultaneously pumping a sodium sulfide aqueous solution, ethyl acetate, 2-furoyl chloride, phosphoric acid, and deionized water into a tubular reactor I to generate an ethyl acetate solution of sodium 2-furoyl thiolate; (b) simultaneously pumping the sodium 2-furanthioate ethyl acetate solution, ethyl acetate, and hydrochloric acid into the tubular reactor II to generate a mixed solution of the sodium 2-furanthioate ethyl acetate solution and water; (c) pumping the mixed solution into a rotary disc extraction tower to separate the ethyl acetate phase and the aqueous phase to obtain a 2-furanmethylthioic acid ethyl acetate solution.

2. The method for preparing the sodium 2-furanthioate ethyl acetate solution according to claim 1, characterized in that In step (a), a catalyst is also added. (a) A sodium sulfide aqueous solution, ethyl acetate, 2-furoyl chloride, phosphoric acid, deionized water, and a catalyst are simultaneously pumped into a tubular reactor I to generate an ethyl acetate solution of sodium 2-furoyl methanethioate.

3. The method for preparing the sodium 2-furanthioate ethyl acetate solution according to claim 2, characterized in that The catalyst is trans-cyclohexyldiamine.

4. The method for preparing the sodium 2-furanthioate ethyl acetate solution according to claim 2, characterized in that In the step (a), the concentration of the sodium sulfide aqueous solution is 10% to 40%.

5. The method for preparing the sodium 2-furanthioate ethyl acetate solution according to claim 1, characterized in that The reaction temperature in step (a) is 10-20°C.

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