Method for synthesizing DL-homocysteine thiolactone hydrochloride through microwave catalysis

Abstract

The invention provides a synthesis method for synthesizing DL-homocysteine thiolactone hydrochloride through microwave catalysis. The synthesis method comprises a preparation method of DL-homocysteine, and the preparation method of the DL-homocysteine comprises the following steps: mixing DL-methionine, water and a solid acid catalyst to obtain a mixed material, and reacting in a microwave catalysis microtube reactor at 85-95 DEG C for 20 minutes to 1 hour; the microwave power in the microwave catalysis microtube reactor is 2 KW, and the wave frequency is 915 Mhz to 2450 Mhz. According to the synthesis method provided by the invention, the DL-homocysteine is synthesized by using specific microwave catalysis, and a specific solid superacid catalyst is preferably combined and used, so that the yield of the homocysteine synthesized by using the DL-methionine without using substances such as hydrofluoric acid and sulfuric acid is improved, the reaction temperature is reduced, the reaction time is shortened, and the yield of the homocysteine is improved. Impurities generated in the reaction process and the carbonization phenomenon are reduced.

Description

Technical Field

[0001] The invention relates to the technical field of pharmaceutical intermediate synthesis, and more specifically to a method for synthesizing DL-homocysteine ​​thiolactone hydrochloride by microwave catalysis. Background Art

[0002] DL-homocysteine ​​thiolactone hydrochloride is one of many amino acid derivatives. It is a white crystalline powder and an important pharmaceutical raw material, intermediate and drug ingredient. It is used to prepare drugs such as erdosteine ​​and cetirizine.

[0003] The Butz team first proposed a method for synthesizing DL-homocysteine ​​by heating DL-methionine with sulfuric acid and has been using it ever since. Since the method has a temperature of 130°C, the reaction temperature is relatively high, and concentrated sulfuric acid has a dehydrating effect, it is easy to dehydrate and carbonize the materials in the reaction system. The theoretical yield of this method using a traditional reactor is only about 55% at most. TAKEHARA JUN disclosed an industrialized production method for DL-homocysteine ​​with a yield of 92%. This method, based on the co-heating of DL-methionine with sulfuric acid, adds hydrobromic acid to react with the by-products to generate DL-methionine again, thereby achieving the purpose of increasing the yield of DL-homocysteine. However, the high-concentration hydrobromic acid wastewater produced in its production process is cumbersome to treat, which causes greater harm to the environment and also increases economic costs.

[0004] Regarding the synthesis of DL-homocysteine ​​thiolactone hydrochloride, it is reported that zinc or tin is used to react with DL-homocysteine ​​in a hydrochloric acid environment to produce it. The product obtained by this method will be doped with metal impurities, which cannot meet the existing medical standards in my country, and these metal impurities are difficult to remove by physical methods to meet the requirements. The use of chemical methods to remove them will increase a large amount of acidic wastewater and cause environmental pollution. The emergence of the electrochemical method for synthesizing DL-homocysteine ​​thiolactone hydrochloride has greatly solved many shortcomings of chemical synthesis. There are literature reports on the method of synthesizing DL-homocysteine ​​salts by constant potential in alkaline media. The production method of DL-homocysteine ​​thiolactone hydrochloride commonly used in industry now is to use a lead electrode as a cathode to electrolyze and synthesize DL-homocysteine ​​thiolactone hydrochloride, but the lead electrode also has heavy metal pollution and does not meet the problem of medical standards. Therefore, there is a great need for the improvement of the decomposition of DL-methionine and the in-situ electrolysis synthesis of DL-homocysteine ​​thiolactone hydrochloride, which can obtain effective value in environmental protection and synthesis efficiency. Summary of the invention

[0005] The first object of the present invention is to provide a method for preparing DL-homocysteine. The method uses specific microwave catalysis to synthesize DL-homocysteine, improves the yield of synthesizing homocysteine ​​using DL-methionine without using hydrofluoric acid, sulfuric acid and other substances, reduces the reaction temperature, shortens the reaction time, and reduces the impurities and carbonization generated during the reaction process.

[0006] The preparation method of DL-homocysteine ​​(as shown in structural formula (III)) provided by the present invention comprises the following steps:

[0007] DL-methionine (as shown in structural formula (I)), water and a solid acid catalyst are mixed to obtain a mixed material, and the mixed material is reacted at 85° C. to 95° C. for 20 minutes to 1 hour under microwave radiation; the microwave power is 2KW and the wave frequency is 915Mhz to 2450Mhz; the solid acid catalyst contains titanium dioxide.

[0008] In the preparation method provided by the present invention, the applicant found that when the temperature is lower than 85°C, the reaction materials are difficult to react completely, and the content of the target product (as shown in structural formula (III)) is low. When the temperature is higher than 95°C, the by-products (as shown in structural formula (II)) increase and the yield of the target product is low.

[0009] In a specific embodiment of the present invention, the solid acid catalyst can be a solid superacid catalyst containing titanium dioxide commonly used in the art. In order to further improve the yield of DL-homocysteine ​​at a lower reaction temperature and a shorter reaction time, the preparation method of the solid acid catalyst can include the following steps:

[0010] Mix titanium dioxide, sodium bromide, methanol and water, add sulfuric acid dropwise at a rate such that the temperature of the system is not higher than 60°C, react at 70-80°C for 5-8h after the addition is completed, distill off the methanol, dry the remaining reaction materials at 110-120°C, bake at 400-450°C for 2-3h, bake at 750-850°C for 4-6h, and cool to obtain the product.

[0011] In the preparation method of the solid acid catalyst, in a preferred embodiment, the molar ratio of titanium dioxide, sodium bromide and sulfuric acid is preferably 3:0.1:(1-1.5).

[0012] In the preparation method of the solid acid catalyst, the concentration of sulfuric acid is usually no more than 70%. In a specific embodiment of the present invention, the concentration of sulfuric acid can be 50%. In a specific embodiment of the present invention, methanol and water are mixed solvents, and the amount of the mixed solvent is preferably 4 to 5 times the mass of titanium dioxide (mL / g). Among them, the volume ratio of methanol and water is preferably (1 to 2): 1. In a specific embodiment, titanium dioxide and sodium bromide can be mixed first, and then a mixed solvent of methanol and water is added. In a specific embodiment of the present invention, the catalyst obtained by cooling is usually recalculated to calculate the proportion of titanium dioxide, and the catalyst is ground and placed in a dryer for standby use.

[0013] In a preferred embodiment of the present invention, in order to further improve the yield of DL-homocysteine, the molar ratio of L-methionine, water, and titanium dioxide in the solid acid catalyst is 1:(8-10):0.5.

[0014] In a specific embodiment of the present invention, microwave irradiation can be achieved by a microwave method commonly used in the art. In a preferred embodiment of the present invention, in order to further improve the yield of DL-homocysteine ​​at a lower reaction temperature and a shorter reaction time, microwave irradiation is achieved by a microwave microtube reactor.

[0015] That is, the present invention provides a method for preparing DL-homocysteine, comprising the following steps: mixing DL-methionine, water and a solid acid catalyst to obtain a mixed material, reacting in a microwave catalytic microtube reactor at 85° C. to 95° C. for 20 min to 1 h; the microwave power in the microwave catalytic microtube reactor is 2 KW, and the wave frequency is 915 Mhz to 2450 Mhz; and the solid acid catalyst contains titanium dioxide.

[0016] In a specific embodiment of the present invention, the microwave catalytic micro-tube reactor comprises:

[0017] Microwave generator, material pipe and cooling pipe;

[0018] The microwave generator is used to provide microwave radiation to the reaction;

[0019] The material pipe is used to transport the mixed material and provide a reaction device for the mixed material;

[0020] The cooling tube is used to control the temperature of the mixed material in the material pipe to be 85° C. to 95° C. In this specific embodiment, the microwave generator provides microwave radiation to the mixed material in the material pipe, the mixed material reacts at 85° C. to 95° C. for 20 minutes to 1 hour in the material pipe, and the cooling tube controls the temperature of the mixed material in the material pipe to be 85° C. to 95° C.

[0021] In a specific embodiment of the present invention, the microwave catalytic micro-tube reactor further comprises a box, the material pipe is arranged in the box, the microwave generator is arranged in the box, the material pipe is made of glass and does not block microwave penetration. In the present invention, the box can be made of stainless steel.

[0022] In a preferred embodiment of the present invention, in order to further improve the yield of DL-homocysteine ​​at a lower reaction temperature and a shorter reaction time, there are four microwave generators, which are respectively arranged at the four corners of the box, and the power of the two microwave generators at one of the diagonals is 2KW, and the wave frequency is 2400Mhz~2450Mhz, and the power of the two microwave generators at the other diagonal is 2KW, and the wave frequency is 915Mhz~920Mhz.

[0023] In a preferred embodiment of the present invention, the cooling pipe is arranged in the material pipe, and the cooling pipe and the material pipe are fixed by a Taylor rosette, and the Taylor rosette has a stirring effect on the mixed material in the material pipe. Figure 2 As shown, the cooling tube 6 is arranged inside the material tube 5, the Taylor rosette 9 is arranged inside the material tube 5, the cooling tube 6 is fixed in the middle of the Taylor rosette 9, the Taylor rosette 9 fixes the cooling tube 6 in the center of the material tube 5, and the Taylor rosette 9 plays a stirring and mixing role on the material in the material tube 5. Among them, the central axis of the cooling tube 6, the material tube 5 and the Taylor rosette 9 can be different, and the central axis of the cooling tube 6, the material tube 5 and the Taylor rosette 9 is preferably the same. Among them, the cooling tube 6 controls the material temperature by cooling water. In a specific embodiment of the present invention, the inner diameter of the material tube 5 is 2 to 3 times the inner diameter of the cooling tube 6. For example, the inner diameter of the material tube 5 can be set to 10mm, and the inner diameter of the cooling tube 6 can be set to 5mm. In the present invention, the cooling tube can be made of tetrafluoroethylene material. In a preferred embodiment of the present invention, the material tube can be placed in a box in a spiral ring, wherein the material tube can be fixed in the box by a support frame. In a preferred embodiment of the present invention, when the material pipe is placed in the box in a spiral shape, in order to make the reaction system in the material pipe heated more evenly, three groups of cooling pipes are evenly arranged according to the actual length of the material pipe.

[0024] In order to better monitor the temperature, a thermometer can be provided on the required equipment as needed. The thermometer is preferably provided outside the box to prevent microwaves from directly irradiating the thermometer.

[0025] In a preferred embodiment of the present invention, the present invention also provides a DL-homocysteine ​​device, comprising a microwave catalytic micro-tube reactor and a metering pump, wherein the metering pump is used to control the reaction of the mixed material for 20 minutes to 1 hour.

[0026] In a preferred embodiment of the present invention, the present invention also provides a DL-homocysteine ​​device, such as Figure 1As shown, it includes a dosing bottle 8, a metering pump 1, a heat exchanger 7, a microwave catalytic microtube reactor 10, a flowmeter 3 and a receiving bottle 2; wherein, the microwave catalytic microtube reactor includes a box body, four microwave generators A, B, C, D, a material pipe 5 and a cooling pipe 6, the material pipe 5 is arranged in the box body, and the four microwave generators A, B, C, D are arranged in the box body.

[0027] like Figure 2 As shown, the cooling pipe 6 is arranged inside the material pipe 5, the Taylor rosette 9 is arranged inside the material pipe 5, the cooling pipe 6 is fixed in the middle of the Taylor rosette 9, the Taylor rosette 9 fixes the cooling pipe 6 in the center of the material pipe 5, and the Taylor rosette 9 plays a stirring and mixing role on the material in the material pipe 5. The inner diameter of the material pipe 5 is 2 to 3 times the inner diameter of the cooling pipe 6. The material pipe 5 is placed in the box in a spiral ring and fixed in the box by the support frame 4. Three groups of cooling pipes 6 are arranged in the material pipe. The temperature of the cooling pipe 6 is controlled by cooling water. Thermometers can be set at the water inlet and outlet of the cooling pipe.

[0028] Microwave generators A, B, C, and D are respectively arranged at the four corners of the box, and the power of microwave generators A and D is 2KW, and the wave frequency is 2400Mhz-2450Mhz, and the power of microwave generators B and C is 2KW, and the wave frequency is 915Mhz-920Mhz. Among them, the materials are mixed in the mixing bottle 8, and each material is pumped into the heat exchanger 7 according to the proportion through the metering pump 1 (a thermometer T0 can be set at the heat exchanger and the metering pump), the heat exchanger 7 is heated by a steam engine, and the steam valve of the heat exchanger is opened to heat the mixed materials, and the discharge temperature of the mixed materials is controlled to be 80℃-85℃. The heat exchanger 7 is connected to the material pipe 5, and the heat exchanger 7 transfers the mixed materials into the material pipe 5. After the mixed materials undergo microwave catalytic reaction in the microwave catalytic micro-tube reactor, they are transferred to the receiving bottle 2, and a flow meter 3 can be set to monitor the speed of the reaction system being transferred to the receiving bottle 2.

[0029] In a specific embodiment of the present invention, when the microwave power is debugged in the early stage of using the device, the incompletely reacted material in the receiving bottle 2 is transported back to the batching bottle 8 through the metering pump. After the debugging is normal, the receiving bottle 2 contains the reaction liquid after the synthesis of DL-homocysteine ​​(referred to as the reaction liquid).

[0030] In a specific embodiment of the present invention, the reaction liquid obtained after the reaction of synthesizing DL-homocysteine ​​is filtered to remove the solid catalyst to obtain a mother liquor, liquid alkali is added to the mother liquor to adjust the pH value of the mother liquor to 7.5-7.8, the precipitated DL-homocysteine ​​is washed with pure water until the sulfate in the pure water is ≤30 ppm (wherein the washing water can be reused for the previous reaction), and dried to obtain DL-homocysteine.

[0031] The conversion rate of homocysteine ​​obtained by the synthesis method provided by the invention is not less than 65%.

[0032] Another object of the present invention is to provide a method for synthesizing DL-homocysteine ​​thiolactone hydrochloride, the method comprising the following steps:

[0033] The DL-homocysteine ​​prepared in the above steps is mixed with hydrochloric acid to prepare a cathode liquid, and a graphite electrode is used as a cathode and an anode, and direct current is used for electrolysis. A reduction reaction occurs at the cathode to generate DL-homocysteine ​​thiolactone hydrochloride as shown in structural formula (IV). The cathode liquid is collected and concentrated under reduced pressure (most of the water is removed) until a large amount of material is precipitated, and DL-homocysteine ​​thiolactone hydrochloride as shown in structural formula (V) is obtained.

[0034]

[0035] In a preferred embodiment of the present invention, the molar ratio of DL-homocysteine ​​to hydrochloric acid is 1:(2-6). In a specific embodiment of the present invention, the concentration of hydrochloric acid can be 30%.

[0036] In a preferred embodiment of the present invention, the electrolysis temperature is 35°C to 50°C, and the current density is 30 mA / ㎡.

[0037] The yield of DL-homocysteine ​​thiolactone hydrochloride obtained by the synthesis method is not less than 95%. Combined with the conversion rate of DL-homocysteine, the overall synthesis yield (based on methionine) of preparing DL-homocysteine ​​thiolactone hydrochloride from DL-methionine is not less than 60%.

[0038] Compared with the prior art, the present invention has the following beneficial effects:

[0039] 1) The present invention provides a continuous production process for synthesizing DL-homocysteine ​​in a microchannel reactor under microwave radiation without using sulfuric acid catalysis and under solid superacid catalysis, then refining DL-homocysteine ​​and then synthesizing DL-homocysteine ​​thiolactone hydrochloride by electrolysis, so that the product yield is improved and the product purity is high, which meets the domestic pharmaceutical standards.

[0040] 2) In the preferred embodiment, the present invention combines microwave catalysis, microchannel continuous, and specific solid superacid TiO2 / SO4 2- / Br 1- Combined with the above, the microwave power is adjusted during the reaction process, the material temperature in the reactor is controlled, and the reaction direction is directed toward the formation of the main product, which shortens the reaction time and reduces the reaction energy consumption. The temperature is controlled to minimize the formation of by-products and reduce the dehydration effect of sulfuric acid, and the appearance color of the reaction liquid is good.

[0041] 3) The entire reaction process provided by the present invention no longer uses sulfuric acid and hydrofluoric acid, which greatly reduces the use of neutralizing liquid alkali. At the same time, a washing step is added to solve the problem of sulfate entrainment in the subsequent electrolysis product, thereby improving the product quality;

[0042] 4) The present invention uses graphite electrodes instead of ordinary lead electrodes, solving the problem of heavy metal content in the product. BRIEF DESCRIPTION OF THE DRAWINGS

[0043] Figure 1 is a diagram of the reaction equipment used in Examples 1 and 2;

[0044] Among them, 1, metering pump; 2, receiving bottle; 3, flow meter; T0~T10 are thermometers; A, B, C, and D are microwave generators; 4, support frame; 5, material pipe; 6, cooling pipe; 7, heat exchanger; 8, batching bottle; 10, microwave catalytic microtube reactor.

[0045] Figure 2 It is a structural diagram of the material pipe 5; among them, 9 is a Taylor rosette. DETAILED DESCRIPTION

[0046] The following examples are used to illustrate the present invention, but are not intended to limit the scope of the present invention.

[0047] The DL-homocysteine ​​equipment used in the specific embodiment of the present invention is as follows: Figure 1 As shown, it includes a batching bottle 8, a metering pump 1, a heat exchanger 7, a microwave catalytic micro-tube reactor 10, a flow meter 3 and a receiving bottle 2; wherein the microwave catalytic micro-tube reactor includes a box, four microwave generators A, B, C, D, a material pipe 5 and a cooling pipe 6, the material pipe 5 is arranged in the box, and the four microwave generators A, B, C, D are arranged in the box. Figure 2 As shown, the cooling pipe 6 is arranged inside the material pipe 5, the Taylor rosette 9 is arranged inside the material pipe 5, the cooling pipe 6 is fixed in the middle of the Taylor rosette 9, the Taylor rosette 9 fixes the cooling pipe 6 in the center of the material pipe 5, and the Taylor rosette 9 stirs and mixes the material in the material pipe 5. The inner diameter of the material pipe 5 is 10 mm, and the inner diameter of the cooling pipe 6 is 5 mm. The material pipe 5 is placed in the box in a spiral ring and fixed in the box by a support frame 4. Three groups of cooling pipes 6 are arranged in the material pipe. The temperature of the cooling pipe 6 is controlled by cooling water. Thermometers can be set at the water inlet and the water outlet of the three groups of cooling pipes. At the same time, thermometers can also be set to test the temperature of the water entering the water inlet and the temperature of the water from the water outlet respectively. In order to better measure the temperature of various places in the material pipe, two thermometers can also be set at appropriate positions. Reference Figure 1In this specific embodiment, 10 thermometers are designed, T0 to T10. The thermometers are all arranged outside the box to avoid direct microwave irradiation of the thermometers.

[0048] Microwave generators A, B, C, and D are respectively arranged at the four corners of the box body. The power of microwave generators A and D is 2KW, and the wave frequency is 2400Mhz~2450Mhz. The power of microwave generators B and C is 2KW, and the wave frequency is 915Mhz~920Mhz.

[0049] Among them, the materials are mixed in the mixing bottle 8, and each material is pumped into the heat exchanger 7 according to the proportion through the metering pump (a thermometer T0 can be set at the heat exchanger and the metering pump), the heat exchanger 7 is heated by a steam engine, the steam valve of the heat exchanger is opened to heat the mixed materials, and the discharge temperature of the mixed materials is controlled to be 80°C to 85°C. The heat exchanger 7 is connected to the material pipe 5, and the heat exchanger 7 transfers the mixed materials into the material pipe 5. After the mixed materials undergo microwave catalytic reaction in the microwave catalytic micro-tube reactor, they are transferred to the receiving bottle 2, and a flow meter 3 can be set to monitor the speed at which the reaction system is transferred to the receiving bottle 2.

[0050] The preparation method of the solid strong catalyst used in the specific embodiment of the present invention comprises the following steps:

[0051] Put 3 mol of solid titanium dioxide and 0.1 mol of sodium bromide into a reaction bottle, put 500 mL of methanol and 500 mL of water into the reaction bottle, control the temperature below 60°C, add 50% sulfuric acid solution (the molar value of sulfuric acid is 1.3 mol), and the drop rate is such that the temperature of the system is not higher than 60°C. After the dropwise addition is completed, stir and react for 7 hours under the reflux state of methanol at 70°C, then evaporate the methanol until the temperature in the reaction system reaches 103°C, stop distillation, and the reaction is over. Pour the remaining materials into a crucible, put it into an oven and heat it to 110°C for drying, then put the crucible into a muffle furnace, bake it at 400°C for 2 hours, then heat it to 750-850°C and bake it for 5 hours, then cool it down and take out the materials, weigh and calculate the proportion of titanium dioxide, grind the catalyst and put it into a dryer for standby use.

[0052] Example 1

[0053] 1) If Figure 1As shown, DL-methionine (structure as shown in structural formula (I)) is mixed with water and solid acid catalyst in a batching bottle 8, and the molar ratio of materials (methionine: water: solid acid catalyst) is 1:8:0.5. After stirring, the materials are mixed evenly, and then pumped into a heat exchanger 7 through a metering pump 1. The steam valve of the heat exchanger 7 is opened to heat the mixed materials, and the discharge temperature of the mixed materials is controlled between 80°C and 85°C. The microwave generators A, B, C, and D are turned on and adjusted to appropriate powers (the powers of microwave generators A, B, C, and D are all 2KW, the wave frequencies of microwave generators A and D are 2450Mhz, and the wave frequencies of microwave generators B and C are 915Mhz). By controlling the cooling water flow and the water inlet temperature of the three groups of cooling jackets 6 in the material pipe 5, the temperature rise of each section is controlled. The temperature at the outlet of the material in the microwave catalytic micro-tube reactor 10 is controlled to be not more than 95° C. at 2 to 3° C., the flow rate of the metering pump 1 is adjusted so that the entire material stays in the microwave catalytic micro-tube reactor 10 for 20 minutes, the entire material circulates in the reaction system for 3 times, and the total reaction time does not exceed 1 hour. After the reaction is completed, the solid catalyst is filtered out to obtain a mother liquor (the bromide ion content in the mother liquor is detected. When the bromide ion content is greater than 1000 ppm, the catalyst needs to be re-reformed), and liquid alkali is added to the mother liquor to adjust the pH value of the mother liquor to 7.5 to 7.8. The precipitated DL-homocysteine ​​is washed with pure water until the sulfate group in the pure water is ≤30 ppm (wherein the washing water can be reused for the previous reaction), and dried to obtain DL-homocysteine. The conversion rate of synthetic homocysteine ​​is 65 to 70%.

[0054] 2) The DL-homocysteine ​​obtained in step 1) is mixed with 30% hydrochloric acid to prepare a cathode liquid, the material molar ratio is 1:3, graphite electrodes are used as cathode and anode, direct current electrolysis is adopted, the electrolyte temperature is controlled between 35° C. and 40° C., the current density is 30 mA / ㎡, the electrolyte circulates in the electrolytic cell, and DL-homocysteine ​​hydrochloride shown in formula (IV) is electrolyzed; then, most of the water is removed by decompression concentration until a large amount of material is precipitated, and DL-homocysteine ​​thiolactone hydrochloride shown in formula (V) is obtained by filtering. The reaction yield reaches 96%.

[0055] Combined with the conversion rate of homocysteine ​​in the first step, the overall synthesis yield (based on methionine) is 62% to 67%.

[0056] Example 2

[0057] 1) If Figure 1As shown, DL-methionine (structure as shown in structural formula (I)) is mixed with water and a catalyst in a mixing bottle 8, and the material molar ratio is (methionine: water: solid acid catalyst = 1:10:0.5). After stirring, the materials are mixed evenly, and then pumped into a heat exchanger 7 through a metering pump 1. The steam valve of the heat exchanger 7 is opened to heat the mixed materials, and the discharge temperature of the mixed materials is controlled between 80°C and 85°C. The microwave generators A, B, C, and D are turned on and adjusted to appropriate power (the power of the microwave generators A, B, C, and D are all 2KW, the wave frequency of the microwave generators A and D is 2450Mhz, and the wave frequency of the microwave generators B and C is 915Mhz). By controlling the cooling water flow rate and the water inlet temperature of the three groups of cooling jackets 6 in the material pipe 5, the temperature rise of each section is controlled. The temperature at the outlet of the material in the microwave catalytic micro-tube reactor 10 is controlled to be not more than 95° C. at 2 to 3° C., the flow rate of the metering pump 1 is adjusted so that the entire material stays in the microwave catalytic micro-tube reactor 10 for 20 minutes, the entire material circulates in the system for 3 times, and the total reaction time does not exceed 1 hour. After the reaction is completed, the solid catalyst is filtered out to obtain a mother liquor (the bromide ion content in the mother liquor is detected. When the bromide ion content is greater than 1000 ppm, the catalyst needs to be re-remelted and re-prepared), liquid alkali is added to the mother liquor to adjust the pH value of the mother liquor to 7.5 to 7.8, the precipitated DL-homocysteine ​​is washed with pure water until the sulfate group in the pure water is ≤30 ppm (wherein, the washing water can be reused for the previous reaction), and DL-homocysteine ​​is dried to obtain the DL-homocysteine, and the conversion rate of the synthetic homocysteine ​​is 70 to 75%.

[0058] 2) preparing a cathode liquid by mixing the DL-homocysteine ​​obtained in step 1) with 30% hydrochloric acid, with a material molar ratio of 1:3, using graphite electrodes as cathode and anode, adopting direct current electrolysis, controlling the electrolyte temperature between 35° C. and 40° C., and the current density at 30 mA / ㎡, the electrolyte circulates in the electrolytic cell, and electrolyzing to generate DL-homocysteine ​​hydrochloride shown in formula (IV); then decompressing and concentrating to remove most of the water until a large amount of material is precipitated, and filtering to obtain DL-homocysteine ​​thiolactone hydrochloride shown in formula (V), and the reaction yield can reach 96%.

[0059] Combined with the conversion rate of homocysteine ​​in the first step, the overall synthesis yield (based on methionine) is between 67% and 72%.

[0060] Finally, the method of the present invention is only a preferred embodiment and is not intended to limit the protection scope of the present invention. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for preparing DL-homocysteine, characterized in that: The steps include: DL-methionine, water and a solid acid catalyst are mixed to obtain a mixed material, and the mixed material is reacted in a microwave catalytic micro-tube reactor at 85°C to 95°C for 20 minutes to 1 hour; the microwave power in the microwave catalytic micro-tube reactor is 2KW, and the wave frequency is 915Mhz to 2450Mhz; the solid acid catalyst contains titanium dioxide.

2. The preparation method according to claim 1, characterized in that: The microwave catalytic micro-tube reactor comprises: Microwave generator, material pipe and cooling pipe; The microwave generator is used to provide microwave radiation to the reaction; The material pipe is used to transport the mixed material and provide a reaction device for the mixed material; The cooling pipe is used to control the temperature of the mixed material in the material pipe to be 85° C. to 95° C.

3. The preparation method according to claim 2, characterized in that: The microwave catalytic micro-tube reactor also includes a casing; The material pipe is arranged in the box body, the microwave generator is arranged in the box body, and the material pipe is made of glass.

4. The preparation method according to claim 3, characterized in that: There are four microwave generators, which are respectively arranged at the four corners of the box. The power of the two microwave generators at one diagonal angle is 2KW, and the wave frequency is 2400Mhz~2450Mhz. The power of the two microwave generators at the other diagonal angle is 2KW, and the wave frequency is 915Mhz~920Mhz.

5. The preparation method according to any one of claims 2 to 4, characterized in that: The cooling pipe is arranged in the material pipe, and the cooling pipe and the material pipe are fixed by a Taylor rosette, and the Taylor rosette has a stirring effect on the mixed material in the material pipe.

6. The preparation method according to claim 1, characterized in that: The preparation method of the solid acid catalyst comprises the following steps: Mix titanium dioxide, sodium bromide, methanol and water, add sulfuric acid dropwise at a rate such that the temperature of the system is not higher than 60°C, react at 70-80°C for 5-8h after the addition is completed, distill off the methanol, dry the remaining reaction materials at 110-120°C, bake at 400-450°C for 2-3h, bake at 750-850°C for 4-6h, and cool to obtain the product.

7. The preparation method according to claim 6, characterized in that: The molar ratio of titanium dioxide, sodium bromide and sulfuric acid is 3:0.1:(1-1.5).

8. The preparation method according to claim 1, 6 or 7, characterized in that: The molar ratio of L-methionine, water and titanium dioxide in the solid acid catalyst is 1:(8-10):0.

5.

9. A method for synthesizing DL-homocysteine ​​thiolactone hydrochloride, characterized in that: The DL-homocysteine ​​obtained by the preparation method according to any one of claims 1 to 8 is mixed with hydrochloric acid to prepare a cathode liquid, a graphite electrode is used as a cathode and an anode, direct current is used for electrolysis, the cathode liquid is collected, and it is concentrated under reduced pressure to obtain the DL-homocysteine ​​thiolactone hydrochloride.

10. The synthesis method according to claim 9, characterized in that The molar ratio of DL-homocysteine ​​to hydrochloric acid is 1:(2-6).

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