Continuous preparation method of sulfonation-extraction coupled phenanthrenequinone sulfonate

Abstract

The invention discloses a sulfonation-extraction coupled phenanthrenequinone sulfonate continuous preparation method, which comprises: preparing a phenanthrenequinone substance solution and a sulfonating agent organic complex solution, and respectively feeding the phenanthrenequinone substance solution and the sulfonating agent organic complex solution through a raw material feeding pipeline, performing sulfonation reaction in a reactor to obtain reaction liquid; mixing the reaction liquid with ultrapure water, and carrying out extraction separation to obtain a mixed solution; and carrying out membrane separation on the mixed solution, adding a sodium salt solution into the obtained supernatant, and mixing to obtain the high-purity phenanthrenequinone sulfonate. The mass transfer and heat transfer efficiency of the sulfonation reaction is effectively improved by utilizing the microreactor, and the reaction yield and the reaction selectivity are greatly improved. According to the invention, the whole treatment process realizes continuous operation, the mixing process is enhanced, the selectivity is improved, and green, safe, efficient and continuous preparation of the phenanthrenequinone sulfonates is realized.

Description

Technical Field

[0001] The invention relates to the field of steroidal compounds, and in particular to a continuous preparation method of sulfonation-extraction coupled phenanthrenequinone sulfonates. Background Art

[0002] Phenanthrenequinone sulfonates play an important role in anti-oxidation, anti-inflammatory, anti-tumor and cardiovascular protection, and are water-soluble, often made into injections for use, and have good clinical application value. Existing phenanthrenequinone sulfonates are mainly prepared using a large amount of sulfonation reagents such as concentrated sulfuric acid. A large amount of highly polluting chemical reagents are required in the preparation process, and polluting gases such as hydrogen chloride are also produced during the production process, which has huge production and environmental pressure. The existing process for preparing phenanthrenequinone sulfonates cannot directly obtain high-purity phenanthrenequinone sulfonates, requires complex post-processing processes, and has low production efficiency. Therefore, it is crucial to develop a continuous preparation method for phenanthrenequinone sulfonates.

[0003] Chinese invention patent CN103739662B discloses a method for preparing sodium tanshinone IIA sulfonate, wherein tanshinone IIA is subjected to a sulfonation reaction with sulfur trioxide or a sulfur trioxide complex in an organic solvent, and the reagent is basically completely consumed after the reaction is completed, and no pollution is caused to the environment, but the purity is not high. Chinese invention patent application CN118271389A discloses a method for preparing sodium tanshinone IIA sulfonate, wherein tanshinone IIA and sulfur trioxide are subjected to a continuous sulfonation reaction in a tubular reactor to obtain a tanshinone IIA sulfonate product, which has the advantages of being green, safe, and efficient, but the product purity is not high and the yield is unstable. Summary of the invention

[0004] The traditional process for producing phenanthrenequinone sulfonates has a complex post-processing process and low product purity. It often needs to go through post-processing processes such as sulfonation, salt formation, centrifugation, washing, filtration, decolorization, drying, and recrystallization to obtain phenanthrenequinone sulfonates with high purity. The process flow is complicated, the cost is high, and a large amount of product loss is caused during the treatment process. The present invention develops a continuous preparation method for phenanthrenequinone sulfonates based on a sulfonation-extraction separation coupling process, which only requires four steps of sulfonation, extraction, salt formation, and filtration. The obtained product yield is as high as 99.1%, and the product purity is more than 99.5%, avoiding the problems of complex post-processing process and low product purity in traditional processes. At the same time, the entire treatment process is realized in a continuous operation, which reduces labor costs and product losses, and realizes the green, safe, and efficient continuous preparation of phenanthrenequinone sulfonates.

[0005] The first aspect of the present invention provides a continuous preparation method of phenanthrenequinone sulfonates by sulfonation-extraction coupling, comprising the following steps:

[0006] A phenanthrenequinone substance solution and an organic complex solution of a sulfonating agent are prepared, and the phenanthrenequinone substance solution and the organic complex solution of the sulfonating agent are subjected to a sulfonation reaction in a sulfonation microreactor to obtain a reaction solution;

[0007] The reaction solution is mixed with ultrapure water, and subjected to extraction and separation to obtain a mixed solution;

[0008] The mixed solution is separated, and a sodium salt solution is added to the obtained supernatant to mix the mixture and perform a salt-forming reaction to obtain a phenanthrenequinone sulfonate.

[0009] As an embodiment, the phenanthrenequinone substance in the phenanthrenequinone substance solution includes at least one of o-phenanthrenequinone or p-phenanthrenequinone. The general structural formula of the phenanthrenequinone substance includes:

[0010] wherein R1 and R2 both include but are not limited to one of furan, thiophene, pyrrole, thiazole, benzofuran, benzene ring, methyl, hydroxyl, and amino.

[0011] As an implementation mode, the phenanthrenequinone substance solution is a solution of phenanthrenequinone substances and an organic solvent.

[0012] As an embodiment, the sulfonating agent in the organic complex solution of the sulfonating agent is sulfur trioxide.

[0013] As an embodiment, the organic solvent and the organic complex include but are not limited to at least one of dichloromethane, 1,2-dichloroethane, tetrachloroethane, N,N-dimethylacetamide, N,N-dimethylformamide, chloroform, 2-methyl sulfoxide, 4-methyl-2-pentanone, tetrahydrofuran, ethyl acetate, methanol, pyrimidine, ether, and methyl tert-butyl ether.

[0014] As an implementation mode, the concentration of the phenanthrenequinone substance solution is 0.01 mol / L-10 mol / L; the concentration of the organic complex solution of the sulfonating agent is 0.01 mol / L-3 mol / L.

[0015] As an implementation mode, the concentration of the phenanthrenequinone substance solution is 0.05mol / L-1mol / L; the concentration of the organic complex solution of the sulfonating agent is 0.1mol / L-0.5mol / L.

[0016] As an embodiment, the concentration of the phenanthrenequinone substance solution is at least one of 0.04mol / L, 0.05mol / L, 0.08mol / L, 0.1mol / L, 0.15mol / L, 0.2mol / L, 0.3mol / L, 0.4mol / L, and 0.5mol / L; the concentration of the organic complex solution of the sulfonating agent is at least one of 0.1mol / L, 0.2mol / L, 0.3mol / L, 0.4mol / L, and 0.5mol / L.

[0017] As an embodiment, the reaction pressure of the sulfonation reaction is 0-5 MPa.

[0018] As an embodiment, the reaction pressure of the sulfonation reaction is 0-3 MPa.

[0019] As an embodiment, the reaction pressure of the sulfonation reaction is at least one of 0 MPa, 0.5 MPa, 1 MPa, 1.5 MPa, 2 MPa, 2.5 MPa, and 3 MPa.

[0020] As an implementation mode, the flow rate of the phenanthrenequinone substance solution is 1 mL / min-5 mL / min, and the flow rate of the organic complex solution of the sulfonating agent is 2 mL / min-6 mL / min.

[0021] As an embodiment, the reaction molar ratio of the phenanthrenequinone substance and sulfur trioxide is 1:(1-30).

[0022] As an embodiment, the reaction molar ratio of the phenanthrenequinone substance to sulfur trioxide is 1:(1-10).

[0023] As an embodiment, the reaction molar ratio of the phenanthrenequinone substance and sulfur trioxide is 1:(1-5).

[0024] As an embodiment, the reaction molar ratio of the phenanthrenequinone substance and sulfur trioxide is at least one of 1:1, 1:1.5, 1:1.75, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, and 1:1.5.

[0025] As an embodiment, the reaction temperature of the sulfonation reaction is 0-60° C., and the residence time of the sulfonation reaction is 0.1-15 min.

[0026] As an embodiment, the reaction temperature of the sulfonation reaction is 20-40° C., and the residence time of the sulfonation reaction is 1-7 min.

[0027] As an embodiment, the reaction temperature of the sulfonation reaction is at least one of 20°C, 25°C, 30°C, 35°C, and 40°C; the residence time of the sulfonation reaction is at least one of 1 min, 2 min, 3 min, 4 min, 5 min, 6 min, and 7 min.

[0028] As an embodiment, the sulfonation reaction is carried out in a sulfonation microreactor, which includes one of an ultrasonic circular microchannel reactor, an ultrasonic rectangular microchannel reactor, an ultrasonic T-shaped microchannel reactor, an ultrasonic heart-shaped microchannel reactor, an ultrasonic umbrella-shaped microchannel reactor, an ultrasonic linear microchannel reactor or an oscillating microchannel reactor.

[0029] As an embodiment, the sulfonation microreactor includes an ultrasonic circular microchannel reactor or an ultrasonic T-shaped microchannel.

[0030] As an embodiment, the material of the sulfonation microreactor includes one of modified polytetrafluoroethylene, Hastelloy, silicon carbide or glass.

[0031] As an embodiment, the retention volume of the sulfonation microreactor is 0.1mL-100mL; the retention volume of the sulfonation microreactor is 10mL-50mL; the retention volume of the sulfonation microreactor is one of 10mL, 20mL, 30mL, 40mL, and 50mL.

[0032] As an embodiment, the ultrasonic power of the sulfonation microreactor is 0W-200W; the ultrasonic power of the sulfonation microreactor is 50W-120W; the ultrasonic power of the sulfonation microreactor is one of 50W, 55W, 60W, 65W, 70W, 75W, 80W, 85W, 90W, 95W, 100W, 110W, and 120W.

[0033] The inventors found during the experiment that the present invention effectively improves the mass transfer and heat transfer efficiency of the sulfonation reaction by using a microreactor, greatly improves the reaction yield and reaction selectivity, the concentration of phenanthrenequinone substances is 0.01-10 mol / L, the concentration of sulfur trioxide is 0.01-3 mol / L, and the reaction molar ratio of phenanthrenequinone substances to sulfur trioxide is 1: (1-30), which can make the transfer and exchange between the reactants more uniform, greatly improving the reaction yield and reaction selectivity.

[0034] As an embodiment, the volume ratio of the supernatant to the sodium salt solution is (2-4):1.

[0035] As an embodiment, the volume ratio of the supernatant to the sodium salt solution is at least one of 2:1, 3:1, and 4:1.

[0036] As an embodiment, the ultrapure water is mixed with the reaction solution through an ultrapure water feed pipe, and the flow rate of the ultrapure water is 0.1-10 mL / min.

[0037] As an embodiment, the ultrapure water is mixed with the reaction solution through an ultrapure water feed pipe, and the flow rate of the ultrapure water is 1-5 mL / min.

[0038] As an embodiment, the flow rate of the ultrapure water is at least one of 1 mL / min, 1.4 mL / min, 1.5 mL / min, 2 mL / min, 2.5 mL / min, 3 mL / min, 3.5 mL / min, 4 mL / min, 4.5 mL / min, and 5 mL / min.

[0039] As an embodiment, the extraction separation is carried out in an extraction microreactor, which includes at least one of a circular microchannel reactor, a rectangular microchannel reactor, a T-shaped microchannel reactor, a heart-shaped microchannel reactor, an umbrella-shaped microchannel reactor or a linear microchannel reactor.

[0040] As an embodiment, the extraction microreactor includes at least one of a circular microchannel reactor or a T-shaped microchannel reactor.

[0041] As an embodiment, the retention volume of the extraction microreactor is 0.1mL-50mL; the retention volume of the extraction microreactor is 5mL-20mL; the retention volume of the extraction microreactor is at least one of 5mL, 10mL, 15mL, and 30mL.

[0042] After the sample is injected into the reaction, pure water is introduced for extraction and separation, thereby improving the purity of the reaction product. The present invention realizes continuous operation of the entire treatment process, strengthens the mixing process, and improves the selectivity. The purity of the prepared phenanthrenequinone sulfonate is greater than 99%, and the yield of the product is greater than 97.5%, thereby realizing the green, safe, efficient and continuous preparation of phenanthrenequinone sulfonates.

[0043] As an embodiment, the separation is carried out in a membrane separator, which includes an upper layer, a middle layer and a lower layer. The upper layer is provided with a liquid inlet and an overflow port, the middle layer is provided with an oil-water separation membrane, and the lower layer is provided with a lower solution storage tank.

[0044] As an embodiment, the oil-water separation membrane includes at least one of a polymer membrane, an inorganic membrane or a metal mesh.

[0045] As an embodiment, the polymer film includes at least one of polyacrylonitrile film, polyvinylidene fluoride film, polyarylether nitrile film, polycaprolactone film, polylactic acid film, polyvinyl alcohol film, polyvinyl chloride film, polyurethane film or polybenzoxazine film.

[0046] As an embodiment, the inorganic membrane includes at least one of a ceramic membrane or a carbonaceous membrane.

[0047] As an embodiment, the metal mesh includes at least one of a copper mesh or a stainless steel mesh.

[0048] As an embodiment, the salt-forming reaction is carried out in a salt-forming microreactor, which includes a circular microchannel reactor, a rectangular microchannel reactor, a T-shaped microchannel reactor, a heart-shaped microchannel reactor, an umbrella-shaped microchannel reactor, a linear microchannel reactor, a spirally curved structure microchannel reactor, an expansion and contraction structure microchannel reactor, a split composite structure microchannel reactor or a periodic static structure microchannel reactor.

[0049] As an embodiment, the salt-forming reaction includes one of a circular microchannel reactor or a split composite structure microchannel reactor.

[0050] As an embodiment, the retention volume of the salt-forming microreactor is 0.1mL-100mL; the retention volume of the salt-forming microreactor is 10mL-25mL; the retention volume of the salt-forming microreactor is one of 10mL, 11mL, 12mL, 13mL, 14mL, 15mL, 16mL, 17mL, 18mL, 19mL, 20mL, 21mL, 22mL, 23mL, 24mL, and 25mL.

[0051] As an embodiment, the sodium salt solution is an inorganic acid sodium salt aqueous solution or an organic acid sodium salt aqueous solution, and the concentration of the sodium salt solution is ≥3 mol / L.

[0052] As an embodiment, the inorganic acid sodium salt aqueous solution includes an inorganic acid sodium salt and water, and the organic acid sodium salt aqueous solution includes an organic acid sodium salt and water.

[0053] As an embodiment, the inorganic acid sodium salt includes at least one of sodium chloride, sodium bromide, sodium iodide, sodium sulfate, sodium bisulfate, sodium carbonate, sodium bicarbonate, sodium nitrate, sodium phosphate, sodium hydrogen phosphate or sodium dihydrogen phosphate.

[0054] As an embodiment, the organic acid sodium salt includes at least one of sodium formate, sodium acetate, sodium oxalate, sodium citrate or sodium benzoate.

[0055] As an embodiment, the concentration of the sodium salt solution is 3-5 mol / L.

[0056] As an embodiment, the continuous preparation method of sulfonation-extraction coupled phenanthrenequinone sulfonates is achieved by a continuous preparation device:

[0057] The continuous preparation device comprises: a phenanthrenequinone substance solution storage tank is connected to a raw material feed pipeline A, a sulfur trioxide solution storage tank is connected to a raw material feed pipeline B, and the other ends of the raw material feed pipeline A and the raw material feed pipeline B are connected to a sulfonation microreactor. An ultrapure water storage tank is connected to the ultrapure water feed pipeline, and the other end of the ultrapure water feed pipeline is connected to the discharge end of the sulfonation microreactor and the extraction microreactor. The discharge end of the extraction microreactor is connected to a membrane separator, a sodium salt solution storage tank is connected to a sodium salt solution feed pipeline, and the other end of the sodium salt solution feed pipeline is connected to the upper discharge end of the membrane separator and the salt-forming microreactor, and the discharge end of the salt-forming microreactor is connected to a product storage tank.

[0058] Compared with the prior art, the present invention has the following beneficial effects:

[0059] (1) The continuous preparation method of phenanthrenequinone sulfonates by sulfonation-extraction coupling of the present invention effectively improves the mass transfer and heat transfer efficiency of the sulfonation reaction by using a microreactor, thereby greatly improving the reaction yield and reaction selectivity.

[0060] (2) In the continuous preparation method of phenanthrenequinone sulfonates by sulfonation-extraction coupling of the present invention, after the reaction solution is mixed with ultrapure water, ultrapure water is used for extraction and separation, thereby improving the purity of the reaction product.

[0061] (3) The continuous preparation method of phenanthrenequinone sulfonates coupled with sulfonation-extraction of the present invention realizes continuous operation of the entire treatment process, strengthens the mixing process, and improves the selectivity. The purity of the prepared phenanthrenequinone sulfonates is greater than 99%, and the yield of the product is greater than 97.5%.

[0062] (4) The continuous preparation method of phenanthrenequinone sulfonates coupled with sulfonation-extraction of the present invention avoids the complicated post-treatment processes such as filtration, washing, decolorization and recrystallization in the traditional process, and realizes the green, safe and efficient continuous preparation of phenanthrenequinone sulfonates.

[0063] (5) The continuous preparation method of sulfonation-extraction coupled phenanthrenequinone sulfonates of the present invention adopts a microreactor to carry out sulfonation reaction, extraction separation reaction and salt formation reaction, which shortens the operation time of the intermittent reaction device, makes the preparation process more economical and efficient, significantly improves production efficiency, and greatly increases the possibility of industrial application. BRIEF DESCRIPTION OF THE DRAWINGS

[0064] Figure 1 Schematic diagram of the continuous preparation device of phenanthrenequinone sulfonates in the example.

[0065] In the figure: 1. Storage tank for phenanthrenequinone solution; 2. Storage tank for sulfur trioxide solution; 3. Raw material feed pipeline A; 4. Raw material feed pipeline B; 5. Sulfonation microreactor; 6. Ultrapure water storage tank; 7. Ultrapure water feed pipeline; 8. Extraction microreactor; 9. Membrane separator; 10. Sodium salt solution storage tank; 11. Sodium salt solution feed pipeline; 12. Salt-forming microreactor; 13. Product storage tank.

[0066] Figure 2 This is a liquid chromatogram of the product prepared in Example 1. DETAILED DESCRIPTION

[0067] Example 1

[0068] A continuous preparation method of phenanthrenequinone sulfonates by sulfonation-extraction coupling, comprising the following steps:

[0069] A phenanthrenequinone substance solution and an organic complex solution of a sulfonating agent are prepared, and the phenanthrenequinone substance solution and the organic complex solution of the sulfonating agent are subjected to a sulfonation reaction in a sulfonation microreactor to obtain a reaction solution;

[0070] The reaction solution is mixed with ultrapure water, and subjected to extraction and separation to obtain a mixed solution;

[0071] The mixed solution is separated, and a sodium salt solution is added to the obtained supernatant to mix the mixture and perform a salt-forming reaction to obtain a phenanthrenequinone sulfonate.

[0072] The phenanthrenequinone substance is tanshinone IIA, and the sulfonating agent is sulfur trioxide.

[0073] The phenanthrenequinone substance solution is a solution of phenanthrenequinone substances and an organic solvent.

[0074] The organic solvent and the organic complex are both dichloromethane.

[0075] The sodium salt solution is a saturated sodium chloride aqueous solution.

[0076] Take tanshinone IIA (0.08 mol) and dissolve it in dichloromethane and dilute it to 1000 mL to obtain a phenanthrenequinone substance solution, which is placed in a phenanthrenequinone substance solution storage tank 1; dissolve 0.05 mol sulfur trioxide in dichloromethane and dilute it to 500 mL to obtain an organic complex solution of a sulfonating agent, which is placed in a sulfur trioxide solution storage tank 2. The flow rate of the raw material feed pipeline A3 is 4.2 mL / min, and the flow rate of the raw material feed pipeline B4 is 5.8 mL / min, entering the sulfonation microreactor 5, the sulfonation temperature is 25°C, the continuous sulfonation reaction time is 2 min, the back pressure valve is adjusted to stabilize the pressure in the sulfonation microreactor 5 at 1.5 MPa, and ultrapure water enters the extraction microreactor 8 from the ultrapure water storage tank 6 through the ultrapure water feed pipeline 7, and the flow rate of ultrapure water is 2 mL / min. The solution at the outlet of the extraction microreactor 8 flows into the membrane separator 9 through the connecting pipe, and the supernatant is taken from the upper overflow port. The sodium salt solution is fed from the sodium salt solution storage tank 10 through the sodium salt solution feeding pipeline 11 and added into the salt-forming microreactor 12 together with the supernatant to fully react (the volume ratio of the sodium salt solution to the supernatant is 1:3). After filtering and drying, sodium tanshinone IIA sulfonate is obtained and placed in the product storage tank 13.

[0077] A constant flow pump is arranged in the middle of the feed pipeline, and the constant flow pump is made of modified polytetrafluoroethylene. The raw material feed pipeline A, the raw material feed pipeline B, and the sodium salt solution feed pipeline are Φ1 / 8 pipelines made of modified polytetrafluoroethylene. The sulfonation microreactor is an ultrasonic circular microreactor with a retention volume of 20 mL. The extraction microreactor is a circular microreactor with a retention volume of 24 mL. The separation membrane in the membrane separator is a self-cleaning polybenzoxazine super-hydrophobic and super-oleophilic mesh membrane.

[0078] The reaction system continued to operate for 15 h, and no blockage was found in the reaction device.

[0079] Example 2

[0080] A continuous preparation method of phenanthrenequinone sulfonates by sulfonation-extraction coupling, comprising the following steps:

[0081] A phenanthrenequinone substance solution and an organic complex solution of a sulfonating agent are prepared, and the phenanthrenequinone substance solution and the organic complex solution of the sulfonating agent are subjected to a sulfonation reaction in a sulfonation microreactor to obtain a reaction solution;

[0082] The reaction solution is mixed with ultrapure water, and subjected to extraction and separation to obtain a mixed solution;

[0083] The mixed solution is separated, and a sodium salt solution is added to the obtained supernatant to mix the mixture and perform a salt-forming reaction to obtain a phenanthrenequinone sulfonate.

[0084] The phenanthrenequinone substance is tanshinone IIA, and the sulfonating agent is sulfur trioxide.

[0085] The phenanthrenequinone substance solution is a solution of phenanthrenequinone substances and an organic solvent.

[0086] The organic solvent and the organic complex are both dichloromethane.

[0087] The sodium salt solution is a sodium chloride aqueous solution with a concentration of 4 mol / L.

[0088] Take tanshinone IIA (0.08 mol) and dissolve it in dichloromethane and dilute it to 1000 mL to obtain a phenanthrenequinone substance solution, which is placed in a phenanthrenequinone substance solution storage tank 1; dissolve 0.1 mol sulfur trioxide in dichloromethane and dilute it to 500 mL to obtain an organic complex solution of a sulfonating agent, which is placed in a sulfur trioxide solution storage tank 2. The flow rate of the raw material feed pipeline A3 is 2.8 mL / min, and the flow rate of the raw material feed pipeline B4 is 4.0 mL / min, entering the sulfonation microreactor 5, the sulfonation temperature is 25°C, the continuous sulfonation reaction time is 2 min, the back pressure valve is adjusted to stabilize the pressure in the sulfonation microreactor 5 at 1.5 MPa, and ultrapure water enters the extraction microreactor 8 from the ultrapure water storage tank 6 through the ultrapure water feed pipeline 7, and the flow rate of ultrapure water is 1.4 mL / min. The solution at the outlet of the extraction microreactor 8 flows into the membrane separator 9 through the connecting pipe, and the supernatant is taken from the upper overflow port. The sodium salt solution is fed from the sodium salt solution storage tank 10 through the sodium salt solution feeding pipeline 11 and added into the salt-forming microreactor 12 together with the supernatant to fully react (the volume ratio of the sodium salt solution to the supernatant is 1:3). After filtering and drying, sodium tanshinone IIA sulfonate is obtained and placed in the product storage tank 13.

[0089] A constant flow pump is arranged in the middle of the feed pipeline, and the constant flow pump is made of modified polytetrafluoroethylene. The raw material feed pipeline A, the raw material feed pipeline B, and the sodium salt solution feed pipeline are Φ1 / 8 pipelines made of modified polytetrafluoroethylene. The sulfonation microreactor is an oscillating T-shaped microreactor with a retention volume of 13.6 mL. The extraction microreactor is a circular microreactor with a retention volume of 8.2 mL. The separation membrane in the membrane separator is a self-cleaning polybenzoxazine super-hydrophobic and super-oleophilic mesh membrane.

[0090] The reaction system continued to operate for 20 h, and no blockage was found in the reaction device.

[0091] Example 3

[0092] A continuous preparation method of phenanthrenequinone sulfonates by sulfonation-extraction coupling, comprising the following steps:

[0093] A phenanthrenequinone substance solution and an organic complex solution of a sulfonating agent are prepared, and the phenanthrenequinone substance solution and the organic complex solution of the sulfonating agent are subjected to a sulfonation reaction in a sulfonation microreactor to obtain a reaction solution;

[0094] The reaction solution is mixed with ultrapure water, and subjected to extraction and separation to obtain a mixed solution;

[0095] The mixed solution is separated, and a sodium salt solution is added to the obtained supernatant to mix the mixture and perform a salt-forming reaction to obtain a phenanthrenequinone sulfonate.

[0096] The phenanthrenequinone substance is 1,2-dihydrotanshinone IIA, and the sulfonating agent is sulfur trioxide.

[0097] The phenanthrenequinone substance solution is a solution of phenanthrenequinone substances and an organic solvent.

[0098] The organic solvent and the organic complex are both dichloromethane.

[0099] The sodium salt solution is a saturated sodium chloride aqueous solution.

[0100] Take 1,2-dihydrotanshinone IIA (0.1 mol) and dissolve it in dichloromethane and adjust the volume to 500 mL to obtain a phenanthrenequinone substance solution, which is placed in a phenanthrenequinone substance solution storage tank 1; dissolve 0.15 mol sulfur trioxide in dichloromethane and adjust the volume to 500 mL to obtain an organic complex solution of a sulfonating agent, which is placed in a sulfur trioxide solution storage tank 2. The flow rate of the raw material feed pipeline A3 is 2.8 mL / min, and the flow rate of the raw material feed pipeline B4 is 4.0 mL / min, entering the sulfonation microreactor 5, the sulfonation temperature is 25°C, the continuous sulfonation reaction time is 2 min, and the back pressure valve is adjusted to stabilize the pressure in the sulfonation microreactor 5 at 0 MPa. Ultrapure water enters the extraction microreactor 8 from the ultrapure water storage tank 6 through the ultrapure water feed pipeline 7, and the flow rate of ultrapure water is 1.4 mL / min. The solution at the outlet of the extraction microreactor 8 flows into the membrane separator 9 through the connecting pipe, and the supernatant is taken from the upper overflow port. The sodium salt solution is fed from the sodium salt solution storage tank 10 through the sodium salt solution feeding pipeline 11 and added into the salt-forming microreactor 12 together with the supernatant to fully react (the volume ratio of the sodium salt solution to the supernatant is 1:3). After filtering and drying, 1,2-dihydrotanshinone IIA sodium sulfonate is obtained and placed in the product storage tank 13.

[0101] A constant flow pump is arranged in the middle of the feed pipeline, and the constant flow pump is made of modified polytetrafluoroethylene. The raw material feed pipeline A, the raw material feed pipeline B, and the sodium salt solution feed pipeline are Φ1 / 16 pipelines made of modified polytetrafluoroethylene. The sulfonation microreactor is an ultrasonic T-shaped microreactor with a retention volume of 13.6 mL. The extraction microreactor is a circular microreactor with a retention volume of 8.2 mL. The separation membrane in the membrane separator is a polyvinylidene fluoride super-hydrophobic and super-oleophilic mesh membrane.

[0102] The reaction system continued to operate for 15 h, and no blockage was found in the reaction device.

[0103] Example 4

[0104] A continuous preparation method of phenanthrenequinone sulfonates by sulfonation-extraction coupling, comprising the following steps:

[0105] A phenanthrenequinone substance solution and an organic complex solution of a sulfonating agent are prepared, and the phenanthrenequinone substance solution and the organic complex solution of the sulfonating agent are subjected to a sulfonation reaction in a sulfonation microreactor to obtain a reaction solution;

[0106] The reaction solution is mixed with ultrapure water, and subjected to extraction and separation to obtain a mixed solution;

[0107] The mixed solution is separated, and a sodium salt solution is added to the obtained supernatant to mix the mixture and perform a salt-forming reaction to obtain a phenanthrenequinone sulfonate.

[0108] The phenanthrenequinone substance is 1,2-dihydrotanshinone IIA, and the sulfonating agent is sulfur trioxide.

[0109] The phenanthrenequinone substance solution is a solution of phenanthrenequinone substances and an organic solvent.

[0110] The organic solvent and the organic complex are both 2-methyl sulfoxide.

[0111] The sodium salt solution is a sodium chloride aqueous solution with a concentration of 4 mol / L.

[0112] Take 1,2-dihydrotanshinone IIA (0.08 mol) and dissolve it with 2-methyl sulfoxide and adjust the volume to 1000 mL to obtain a phenanthrenequinone substance solution, which is placed in a phenanthrenequinone substance solution storage tank 1; dissolve 0.05 mol sulfur trioxide with 2-methyl sulfoxide and adjust the volume to 500 mL to obtain an organic complex solution of a sulfonating agent, which is placed in a sulfur trioxide solution storage tank 2. The flow rate of the raw material feed pipeline A3 is 3.4 mL / min, and the flow rate of the raw material feed pipeline B4 is 3.4 mL / min, entering the sulfonation microreactor 5, the sulfonation temperature is 20°C, the continuous sulfonation reaction time is 2 min, and the back pressure valve is adjusted to stabilize the pressure in the sulfonation microreactor 5 at 1.0 MPa. Ultrapure water enters the extraction microreactor 8 from the ultrapure water storage tank 6 through the ultrapure water feed pipeline 7, and the flow rate of ultrapure water is 1.4 mL / min. The solution at the outlet of the extraction microreactor 8 flows into the membrane separator 9 through the connecting pipe, and the supernatant is taken from the upper overflow port. The sodium salt solution is fed from the sodium salt solution storage tank 10 through the sodium salt solution feeding pipeline 11 and added into the salt-forming microreactor 12 together with the supernatant to fully react (the volume ratio of the sodium salt solution to the supernatant is 1:3). After filtering and drying, 1,2-dihydrotanshinone IIA sodium sulfonate is obtained and placed in the product storage tank 13.

[0113] A constant flow pump is arranged in the middle of the feed pipe, and the constant flow pump is made of Hastelloy. The raw material feed pipe A, the raw material feed pipe B, and the sodium salt solution feed pipe are Φ3 / 16 pipes made of Hastelloy. The sulfonation microreactor is an ultrasonic Bagua-shaped microreactor with a retention volume of 13.6 mL. The extraction microreactor is a circular microreactor with a retention volume of 8.2 mL. The separation membrane in the membrane separator is a self-cleaning polybenzoxazine super-hydrophobic and super-oleophilic mesh membrane.

[0114] The reaction system continued to operate for 15 h, and no blockage was found in the reaction device.

[0115] Example 5

[0116] A continuous preparation method of phenanthrenequinone sulfonates by sulfonation-extraction coupling, comprising the following steps:

[0117] A phenanthrenequinone substance solution and an organic complex solution of a sulfonating agent are prepared, and the phenanthrenequinone substance solution and the organic complex solution of the sulfonating agent are subjected to a sulfonation reaction in a sulfonation microreactor to obtain a reaction solution;

[0118] The reaction solution is mixed with ultrapure water, and subjected to extraction and separation to obtain a mixed solution;

[0119] The mixed solution is separated, and a sodium salt solution is added to the obtained supernatant to mix the mixture and perform a salt-forming reaction to obtain a phenanthrenequinone sulfonate.

[0120] The phenanthrenequinone substance is tanshinone I, and the sulfonating agent is sulfur trioxide.

[0121] The organic solvent and the organic complex are both ethylene dichloride.

[0122] The sodium salt solution is a sodium chloride aqueous solution with a concentration of 3 mol / L.

[0123] Take tanshinone I (0.15 mol) and dissolve it in dichloroethane and adjust the volume to 500 mL to obtain a phenanthrenequinone substance solution, which is placed in a phenanthrenequinone substance solution storage tank 1; dissolve 0.25 mol sulfur trioxide in dichloroethane and adjust the volume to 500 mL to obtain an organic complex solution of a sulfonating agent, which is placed in a sulfur trioxide solution storage tank 2. The flow rate of the raw material feed pipeline A3 is 2.0 mL / min, and the flow rate of the raw material feed pipeline B4 is 4.0 mL / min, entering the sulfonation microreactor 5, the sulfonation temperature is 30°C, the continuous sulfonation reaction time is 4 minutes, and the back pressure valve is adjusted to stabilize the pressure in the sulfonation microreactor 5 at 0.5 MPa. Ultrapure water enters the extraction microreactor 8 from the ultrapure water storage tank 6 through the ultrapure water feed pipeline 7, and the flow rate of ultrapure water is 2 mL / min. The solution at the outlet of the extraction microreactor 8 flows into the membrane separator 9 through the connecting pipe, and the supernatant is taken from the upper overflow port. The sodium salt solution is fed from the sodium salt solution storage tank 10 through the sodium salt solution feeding pipeline 11 and added into the salt-forming microreactor 12 together with the supernatant to fully react (the volume ratio of the sodium salt solution to the supernatant is 1:2). After filtering and drying, sodium tanshinone I sulfonate is obtained and placed in the product storage tank 13.

[0124] A constant flow pump is arranged in the middle of the feed pipeline, and the constant flow pump is made of modified polytetrafluoroethylene. The raw material feed pipeline A, the raw material feed pipeline B, and the sodium salt solution feed pipeline are Φ1 / 8 pipelines made of Hastelloy material. The sulfonation microreactor is an ultrasonic T-shaped microreactor with a retention volume of 24 mL. The extraction microreactor is a T-shaped microreactor with a retention volume of 8.0 mL. The separation membrane in the membrane separator is a self-cleaning polybenzoxazine super-hydrophobic and super-oleophilic mesh membrane.

[0125] The reaction system continued to operate for 10 h, and no blockage was found in the reaction device.

[0126] Example 6

[0127] A continuous preparation method of phenanthrenequinone sulfonates by sulfonation-extraction coupling, comprising the following steps:

[0128] A phenanthrenequinone substance solution and an organic complex solution of a sulfonating agent are prepared, and the phenanthrenequinone substance solution and the organic complex solution of the sulfonating agent are subjected to a sulfonation reaction in a sulfonation microreactor to obtain a reaction solution;

[0129] The reaction solution is mixed with ultrapure water, and subjected to extraction and separation to obtain a mixed solution;

[0130] The mixed solution is separated, and a sodium salt solution is added to the obtained supernatant to mix the mixture and perform a salt-forming reaction to obtain a phenanthrenequinone sulfonate.

[0131] The phenanthrenequinone substance is tanshinone I, and the sulfonating agent is sulfur trioxide.

[0132] The organic solvent and the organic complex are both petroleum ether.

[0133] The sodium salt solution is a sodium chloride aqueous solution with a concentration of 3 mol / L.

[0134] Take tanshinone I (0.2 mol) and dissolve it in petroleum ether and dilute it to 500 mL to obtain a phenanthrenequinone substance solution, which is placed in a phenanthrenequinone substance solution storage tank 1; dissolve 0.3 mol sulfur trioxide in petroleum ether and dilute it to 500 mL to obtain an organic complex solution of a sulfonating agent, which is placed in a sulfur trioxide solution storage tank 2. The flow rate of the raw material feed pipeline A3 is 1.5 mL / min, and the flow rate of the raw material feed pipeline B4 is 2.5 mL / min, entering the sulfonation microreactor 5, the sulfonation temperature is 25°C, the continuous sulfonation reaction time is 2 min, and the back pressure valve is adjusted to stabilize the pressure in the sulfonation microreactor 5 at 0.5 MPa. Ultrapure water enters the extraction microreactor 8 from the ultrapure water storage tank 6 through the ultrapure water feed pipeline 7, and the flow rate of ultrapure water is 1 mL / min. The solution at the outlet of the extraction microreactor 8 flows into the membrane separator 9 through the connecting pipe, and the supernatant is taken from the upper overflow port. The sodium salt solution is fed from the sodium salt solution storage tank 10 through the sodium salt solution feeding pipeline 11 and added into the salt-forming microreactor 12 together with the supernatant to fully react (the volume ratio of the sodium salt solution to the supernatant is 1:2). After filtering and drying, sodium tanshinone I sulfonate is obtained and placed in the product storage tank 13.

[0135] A constant flow pump is arranged in the middle of the feed pipe, and the constant flow pump is made of modified polytetrafluoroethylene. The raw material feed pipe A, the raw material feed pipe B, and the sodium salt solution feed pipe are Φ1 / 4 pipes made of Hastelloy material. The sulfonation microreactor is an ultrasonic rectangular microreactor with a retention volume of 8 mL. The extraction microreactor is a circular microreactor with a retention volume of 5.0 mL. The separation membrane in the membrane separator is a self-cleaning polybenzoxazine super-hydrophobic and super-oleophilic mesh membrane.

[0136] The reaction system continued to operate for 14 h, and no blockage was found in the reaction device.

[0137] Example 7

[0138] A continuous preparation method of phenanthrenequinone sulfonates by sulfonation-extraction coupling, comprising the following steps:

[0139] A phenanthrenequinone substance solution and an organic complex solution of a sulfonating agent are prepared, and the phenanthrenequinone substance solution and the organic complex solution of the sulfonating agent are subjected to a sulfonation reaction in a sulfonation microreactor to obtain a reaction solution;

[0140] The reaction solution is mixed with ultrapure water, and subjected to extraction and separation to obtain a mixed solution;

[0141] The mixed solution is separated, and a sodium salt solution is added to the obtained supernatant to mix the mixture and perform a salt-forming reaction to obtain a phenanthrenequinone sulfonate.

[0142] The phenanthrenequinone substance is methyl salvia miltiorrhiza, and the sulfonating agent is sulfur trioxide.

[0143] The organic solvent and the organic complex are both ether.

[0144] The sodium salt solution is a sodium chloride aqueous solution with a concentration of 3 mol / L.

[0145] Take salvia miltiorrhiza acid methyl ester (0.3 mol) and dissolve it with ether and dilute it to 500 mL to obtain a phenanthrenequinone substance solution, which is placed in a phenanthrenequinone substance solution storage tank 1; dissolve 0.5 mol sulfur trioxide with ether and dilute it to 500 mL to obtain an organic complex solution of a sulfonating agent, which is placed in a sulfur trioxide solution storage tank 2. The flow rate of the raw material feed pipeline A3 is 2 mL / min, and the flow rate of the raw material feed pipeline B4 is 3 mL / min, entering the sulfonation microreactor 5, the sulfonation temperature is 25 ° C, the continuous sulfonation reaction time is 2 min, the back pressure valve is adjusted to stabilize the pressure in the sulfonation microreactor 5 at 0 MPa, and ultrapure water enters the extraction microreactor 8 from the ultrapure water storage tank 6 through the ultrapure water feed pipeline 7, and the flow rate of ultrapure water is 1.4 mL / min. The solution at the outlet of the extraction microreactor 8 flows into the membrane separator 9 through the connecting pipe, and the supernatant is taken from the upper overflow port. The sodium salt solution is fed from the sodium salt solution storage tank 10 through the sodium salt solution feeding pipeline 11 and added into the salt-forming microreactor 12 together with the supernatant to fully react (the volume ratio of the sodium salt solution to the supernatant is 1:3). After filtering and drying, sodium methyl salvianolic acid sulfonate is obtained and placed in the product storage tank 13.

[0146] A constant flow pump is arranged in the middle of the feed pipe, and the constant flow pump is made of modified polytetrafluoroethylene. The raw material feed pipe A, the raw material feed pipe B, and the sodium salt solution feed pipe are Φ1 / 4 pipes made of Hastelloy material. The sulfonation microreactor is an ultrasonic rectangular microreactor with a retention volume of 8 mL. The extraction microreactor is a circular microreactor with a retention volume of 5.0 mL. The separation membrane in the membrane separator is a self-cleaning polybenzoxazine super-hydrophobic and super-oleophilic mesh membrane.

[0147] The reaction system continued to operate for 14 h, and no blockage was found in the reaction device.

[0148] Example 8

[0149] A continuous preparation method of phenanthrenequinone sulfonates by sulfonation-extraction coupling, comprising the following steps:

[0150] A phenanthrenequinone substance solution and an organic complex solution of a sulfonating agent are prepared, and the phenanthrenequinone substance solution and the organic complex solution of the sulfonating agent are subjected to a sulfonation reaction in a sulfonation microreactor to obtain a reaction solution;

[0151] The reaction solution is mixed with ultrapure water, and subjected to extraction and separation to obtain a mixed solution;

[0152] The mixed solution is separated, and a sodium salt solution is added to the obtained supernatant to mix the mixture and perform a salt-forming reaction to obtain a phenanthrenequinone sulfonate.

[0153] The phenanthrenequinone substance is methyl salvia miltiorrhiza, and the sulfonating agent is sulfur trioxide.

[0154] The organic solvent and the organic complex are both tetrahydrofuran.

[0155] The sodium salt solution is a saturated sodium chloride aqueous solution.

[0156] Take methyl salvia miltiorrhiza (0.04mol) and dissolve it in tetrahydrofuran and make it to 500mL to obtain a phenanthrenequinone substance solution, which is placed in a phenanthrenequinone substance solution storage tank 1; dissolve 0.05mol sulfur trioxide in tetrahydrofuran and make it to 500mL to obtain an organic complex solution of a sulfonating agent, which is placed in a sulfur trioxide solution storage tank 2. The flow rate of the raw material feed pipeline A3 is 2.2mL / min, and the flow rate of the raw material feed pipeline B4 is 4.8mL / min, which enters the sulfonation microreactor 5, the sulfonation temperature is 25°C, the continuous sulfonation reaction time is 3min, the back pressure valve is adjusted to stabilize the pressure in the sulfonation microreactor 5 at 1.0MPa, and ultrapure water enters the extraction microreactor 8 from the ultrapure water storage tank 6 through the ultrapure water feed pipeline 7, and the flow rate of ultrapure water is 3mL / min. The solution at the outlet of the extraction microreactor 8 flows into the membrane separator 9 through the connecting pipe, and the supernatant is taken from the upper overflow port. The sodium salt solution is fed from the sodium salt solution storage tank 10 through the sodium salt solution feeding pipeline 11 and added into the salt-forming microreactor 12 together with the supernatant to fully react (the volume ratio of the sodium salt solution to the supernatant is 1:3). After filtering and drying, sodium methyl salvianolic acid sulfonate is obtained and placed in the product storage tank 13.

[0157] A constant flow pump is arranged in the middle of the feed pipe, and the constant flow pump is made of Hastelloy. The raw material feed pipe A, the raw material feed pipe B, and the sodium salt solution feed pipe are Φ1 / 8 pipes made of modified polytetrafluoroethylene. The sulfonation microreactor is an ultrasonic circular microreactor with a retention volume of 21 mL. The extraction microreactor is a circular microreactor with a retention volume of 10.0 mL. The separation membrane in the membrane separator is a self-cleaning polybenzoxazine super-hydrophobic and super-oleophilic mesh membrane.

[0158] The reaction system continued to operate for 15 h, and no blockage was found in the reaction device.

[0159] Example 9

[0160] A continuous preparation method of phenanthrenequinone sulfonates by sulfonation-extraction coupling, comprising the following steps:

[0161] A phenanthrenequinone substance solution and an organic complex solution of a sulfonating agent are prepared, and the phenanthrenequinone substance solution and the organic complex solution of the sulfonating agent are subjected to a sulfonation reaction in a sulfonation microreactor to obtain a reaction solution;

[0162] The reaction solution is mixed with ultrapure water, and subjected to extraction and separation to obtain a mixed solution;

[0163] The mixed solution is separated, and a sodium salt solution is added to the obtained supernatant to mix the mixture and perform a salt-forming reaction to obtain a phenanthrenequinone sulfonate.

[0164] The phenanthrenequinone substance is methyl salvia miltiorrhiza, and the sulfonating agent is sulfur trioxide.

[0165] The organic solvent and the organic complex are both dichloromethane.

[0166] The sodium salt solution is a saturated sodium chloride aqueous solution.

[0167] Take salvia miltiorrhiza acid methyl ester (0.04mol) and dissolve it in dichloromethane and dilute it to 500mL to obtain a phenanthrenequinone substance solution, which is placed in a phenanthrenequinone substance solution storage tank 1; dissolve 0.05mol sulfur trioxide in dichloromethane and dilute it to 500mL to obtain an organic complex solution of a sulfonating agent, which is placed in a sulfur trioxide solution storage tank 2. The flow rate of the raw material feed pipeline A3 is 4.2mL / min, and the flow rate of the raw material feed pipeline B4 is 5.8mL / min, entering the sulfonation microreactor 5, the sulfonation temperature is 25°C, the continuous sulfonation reaction time is 2min, the back pressure valve is adjusted to stabilize the pressure in the sulfonation microreactor 5 at 1.5MPa, and ultrapure water enters the extraction microreactor 8 from the ultrapure water storage tank 6 through the ultrapure water feed pipeline 7, and the flow rate of ultrapure water is 2mL / min. The solution at the outlet of the extraction microreactor 8 flows into the membrane separator 9 through the connecting pipe, and the supernatant is taken from the upper overflow port. The sodium salt solution is fed from the sodium salt solution storage tank 10 through the sodium salt solution feeding pipeline 11 and added into the salt-forming microreactor 12 together with the supernatant to fully react (the volume ratio of the sodium salt solution to the supernatant is 1:4). After filtering and drying, sodium methyl salvianolic acid sulfonate is obtained and placed in the product storage tank 13.

[0168] A constant flow pump is arranged in the middle of the feed pipeline, and the constant flow pump is made of modified polytetrafluoroethylene. The raw material feed pipeline A, the raw material feed pipeline B, and the sodium salt solution feed pipeline are Φ3 / 16 pipelines made of modified polytetrafluoroethylene. The sulfonation microreactor is an oscillating microreactor with a retention volume of 20 mL. The extraction microreactor is a circular microreactor with a retention volume of 12 mL. The separation membrane in the membrane separator is a self-cleaning polybenzoxazine super-hydrophobic and super-oleophilic mesh membrane.

[0169] The reaction system continued to operate for 15 h, and no blockage was found in the reaction device.

[0170] Comparative Example 1

[0171] Take tanshinone IIA (0.004 mol) and dissolve it in dichloromethane and dilute it to 50 mL, then pour it into a 250 mL three-necked flask; and add 15 mL of chlorosulfonic acid to the three-necked flask. Insert a thermometer below the liquid level of the flask, put the flask into a water bath, maintain a constant temperature of 20°C, and continue the reaction for 1 hour. After the reaction is completed, immediately add 25 mL of saturated salt water, filter and dry to obtain sodium tanshinone IIA sulfonate.

[0172] Comparative Example 2

[0173] Take 5g of methyl salvianolic acid, add 36mL of glacial acetic acid and 6mL of acetic anhydride, place in a 100mL three-necked flask, insert a thermometer below the liquid level of the flask, put the flask in a water bath, maintain a constant temperature of 20℃, and slowly add 2mL of a mixture of concentrated sulfuric acid and glacial acetic acid (volume ratio of 1:1) under magnetic stirring. After the addition is completed, stir magnetically for 1.5h, then immediately add 30mL of saturated sodium chloride aqueous solution, filter and dry to obtain sodium salvianolic acid methyl ester sulfonate.

[0174] Comparative Example 3

[0175] Take tanshinone I (0.025 mol) and dissolve it in dichloromethane and dilute it to 500 mL, add 20g 3A molecular sieve, and let it stand for 24 hours to obtain a phenanthrenequinone solution; dissolve 0.05 mol sulfur trioxide in dichloromethane and dilute it to 500 mL to obtain an organic complex solution of a sulfonating agent. The injection flow rate of the phenanthrenequinone solution is controlled to be 4.4 mL / min, and the injection flow rate of the organic complex solution of the sulfonating agent is controlled to be 5.6 mL / min. The sulfonation temperature is controlled to be 25°C, and the residence time of the continuous sulfonation reaction is 2 min. Adjust the back pressure valve to stabilize the pressure in the sulfonation microreactor at 1 MPa, add saturated brine (the volume ratio of saturated brine to the volume of the reaction solution is 1:4), and filter and dry to obtain sodium tanshinone I sulfonate.

[0176] The reaction lasted only 0.5 h and the reaction apparatus was completely blocked.

[0177] Performance Testing

[0178] The product was subjected to liquid chromatography detection. The liquid chromatogram of the product prepared in Example 1 is shown in FIG. Figure 2 The peak with a retention time of 18.638 min in the figure is the characteristic peak of sodium tanshinone IIA sulfonate, and the product yield and purity are calculated by the standard curve method. The products of the embodiments and comparative examples are detected by liquid chromatography to test the product yield and purity. The test results are shown in Table 1.

[0179] Table 1

[0180] Yield / % purity / % Example 1 95.5 97.6 Example 2 99.1 99.5 Example 3 97.8 98.5 Example 4 91.6 92.9 Example 5 85.6 86.4 Example 6 86.6 87.4 Example 7 93.6 92.4 Example 8 94.5 95.6 Example 9 91.5 90.1 Comparative Example 1 28.8 20.4 Comparative Example 2 59.79 45.4 Comparative Example 3 80.3 58.2

[0181] Comparative Examples 1 and 2 are different from Examples 1-9. Examples 1-9 are all continuous flow processes, while Comparative Examples 1 and 2 are intermittent processes. It can be seen that the equipment and preparation method provided by the present invention are simpler and safer, the amount of sulfonating agent used is small, the yield and purity of the prepared target product are higher, and continuous production can be carried out; Comparative Example 3 is a continuous flow process. Compared with Examples 1-9, it can be seen that the yield and purity of the target product of the present invention are higher, the complex post-processing process can be avoided, and the operating time of the device is greatly extended, the preparation process is more economical and efficient, the production efficiency is significantly improved, and the possibility of industrial application is greatly improved.

Claims

1. A continuous preparation method of phenanthrenequinone sulfonates by sulfonation-extraction coupling, characterized in that: The following steps are involved: A phenanthrenequinone substance solution and an organic complex solution of a sulfonating agent are prepared, and the phenanthrenequinone substance solution and the organic complex solution of the sulfonating agent are subjected to a sulfonation reaction in a sulfonation microreactor to obtain a reaction solution; The reaction solution is mixed with ultrapure water, and subjected to extraction and separation to obtain a mixed solution; The mixed solution is separated, and the obtained supernatant is added with a sodium salt solution and mixed to carry out a salt-forming reaction to obtain a phenanthrenequinone sulfonate.

2. The continuous preparation method of phenanthrenequinone sulfonates by sulfonation-extraction coupling according to claim 1, characterized in that: The sulfonating agent in the organic complex solution of the sulfonating agent is sulfur trioxide.

3. The continuous preparation method of phenanthrenequinone sulfonates by sulfonation-extraction coupling according to claim 1, characterized in that: The concentration of the phenanthrenequinone substance solution is 0.01 mol / L-10 mol / L; the concentration of the organic complex solution of the sulfonating agent is 0.01 mol / L-3 mol / L.

4. The continuous preparation method of phenanthrenequinone sulfonates by sulfonation-extraction coupling according to claim 1, characterized in that: The reaction pressure of the sulfonation reaction is 0MPa-5MPa.

5. The continuous preparation method of phenanthrenequinone sulfonates by sulfonation-extraction coupling according to claim 1, characterized in that: The flow rate of the phenanthrenequinone substance solution is 1 mL / min-5 mL / min, and the flow rate of the organic complex solution of the sulfonating agent is 2 mL / min-6 mL / min.

6. The continuous preparation method of phenanthrenequinone sulfonates by sulfonation-extraction coupling according to claim 1, characterized in that: The reaction temperature of the sulfonation reaction is 0°C-60°C, and the residence time of the sulfonation reaction is 0.1min-15min.

7. The continuous preparation method of phenanthrenequinone sulfonates by sulfonation-extraction coupling according to claim 1, characterized in that: The volume ratio of the supernatant to the sodium salt solution is (2-4):

1.

8. The continuous preparation method of phenanthrenequinone sulfonates by sulfonation-extraction coupling according to claim 1, characterized in that: The flow rate of the ultrapure water is 0.1 mL / min-10 mL / min.

9. The continuous preparation method of phenanthrenequinone sulfonates by sulfonation-extraction coupling according to claim 1, characterized in that: The sodium salt solution is an inorganic acid sodium salt aqueous solution or an organic acid sodium salt aqueous solution, and the concentration of the sodium salt solution is ≥3 mol / L.

10. The continuous preparation method of phenanthrenequinone sulfonates by sulfonation-extraction coupling according to claim 9, characterized in that: The inorganic acid sodium salt aqueous solution comprises an inorganic acid sodium salt and water, and the inorganic acid sodium salt comprises at least one of sodium chloride, sodium bromide, sodium iodide, sodium sulfate, sodium bisulfate, sodium carbonate, sodium bicarbonate, sodium nitrate, sodium phosphate, sodium hydrogen phosphate or sodium dihydrogen phosphate.

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