Thiadiazole synthesis process

Abstract

The invention provides a thiadiazole synthesis process. The thiadiazole synthesis process comprises the following steps: a condensation section: A1) before feeding, carefully checking whether a dithiourea reaction kettle R13001, a stirrer, water supply, steam supply and power supply are normal or not and whether a valve has a leakage phenomenon or not; a2) hydrazine hydrate is pumped into a hydrazine hydrate metering tank V13003 through a feeding pump P13005, concentrated sulfuric acid is pumped into a concentrated sulfuric acid metering tank V13001 from a sulfuric acid storage tank V34301 through a material transfer pump P34301, and metering should be accurate; a3) putting water metered by a flow meter into a reaction kettle R13001, starting a stirrer, opening a bottom valve of a concentrated sulfuric acid metering tank V13001, and putting concentrated sulfuric acid into the reaction kettle R13001; and A4) when the temperature in the reaction kettle R13001 is lower than 60 DEG C, opening a bottom valve of a hydrazine hydrate metering tank V13003, and slowly dropwise adding a hydrazine hydrate solution. The thiadiazole synthesis process provided by the invention has the advantages that the synthesis reaction time is shortened, the reaction temperature is reduced, the yield is improved, and byproducts are reduced.

Description

Technical Field

[0001] The invention relates to the technical field of thiadiazole synthesis, and in particular to a thiadiazole synthesis process. Background Art

[0002] Thiadiazole is an important organic synthesis intermediate, widely used in medicine, pesticides, dyes and organic synthesis. It is also an important intermediate for the production of cefazolin, cefcanep, cefazolin, oxazolidinone cephalosporin, cefoperazone, cephalosporin BL-S339, furazolidinone cephalosporin and other medicines. Because this type of drug has a broad antibacterial spectrum, good absorption, few side effects, and is particularly suitable for oral absorption, it is widely used in clinical practice.

[0003] However, the current process of synthesizing thiadiazoles has the disadvantages of long reaction time, high reaction temperature, low yield, and many by-products.

[0004] Therefore, it is necessary to provide a new thiadiazole synthesis process to solve the above technical problems. Summary of the invention

[0005] In order to solve the technical problems of long reaction time, high reaction temperature, low yield and many by-products in the current synthesis of thiadiazoles, the present invention provides a thiadiazole synthesis process.

[0006] The thiadiazole synthesis process provided by the present invention comprises the following steps:

[0007] Condensation section:

[0008] A1) Before feeding, carefully check whether the dithiourea reactor R13001 and the mixer as well as the water supply, steam supply and power supply are normal, and whether there is any leakage in the valve;

[0009] A2) Pump hydrazine hydrate into hydrazine hydrate metering tank V13003 via feed pump P13005, and pump concentrated sulfuric acid from sulfuric acid storage tank V34301 into concentrated sulfuric acid metering tank V13001 via transfer pump P34301. The metering should be accurate.

[0010] A3) First, water measured by a flow meter is put into the reactor R13001, and the stirrer is turned on, and then the bottom valve of the concentrated sulfuric acid metering tank V13001 is opened to put the concentrated sulfuric acid into the reactor R13001;

[0011] A4) When the temperature in the reactor R13001 is lower than 60°C, open the bottom valve of the hydrazine hydrate metering tank V13003 and slowly add the hydrazine hydrate solution;

[0012] A5) After the addition of hydrazine hydrate is completed, the feed hole of reactor R13001 is opened, the pre-crushed ammonium thiocyanate is added at one time, and after the solid catalyst and the water-carrying acetone are added, the feed hole is closed and the water inlet valve of condenser E13001 is opened;

[0013] A6) Open the jacket steam valve of reactor R13001 and heat it. When the temperature in reactor R13001 rises to 45-55°C, immediately close the steam valve. The reaction time is 1-1.5h.

[0014] A7) After the temperature reaction is completed, the steam is turned on to slowly increase the temperature until a steady reflux reaction occurs, and the reflux reaction is maintained;

[0015] A8) After the reflux reaction is completed, the steam valve is closed, and the jacket water inlet valve is opened to perform cooling crystallization;

[0016] A9) Open the discharge valve at the bottom of reactor R13001 and pump the material into dithiourea turnover tank V12001 through the discharge pump P13001, open the bottom valve of turnover tank V12001 and pump the material into dithiourea centrifuge M12002 through the turnover pump P12001 for centrifugal drying; weigh, send samples for analysis, and calculate the yield of dithiourea; after centrifugation, rinse reactor R13001 and wait for the next feeding;

[0017] A10) The ammonium sulfate wastewater and centrifugal washing water produced by the dithiourea condensation reaction are concentrated into the dithiourea mother liquor collection tank V12004, and pumped into the wastewater collection tank through the mother liquor pump P12004 for desalination pretreatment and then biochemical treatment;

[0018] Ring Closing Section:

[0019] B1) Before feeding, carefully check whether the thiadiazole reactor R13002 and the mixer as well as the water, steam and power supply are normal, and whether there is any leakage in the valve;

[0020] B2) Pump hydrochloric acid from the hydrochloric acid storage tank V34302 into the hydrochloric acid metering tank V13004 via the transfer pump P34302. The metering should be accurate.

[0021] B3) firstly put the water measured by the flow meter into the reactor R13002, and start the stirrer, then open the bottom valve of the hydrochloric acid metering tank V13004 to put the hydrochloric acid into the reactor R13002, then put the dithiourea and the solid catalyst into the reactor R13002, and close the feed hole;

[0022] B4) Start the stirrer, open the water inlet valve of condenser E13002, and open the jacket steam valve of reactor R13002 to heat;

[0023] B5) slowly heating the steam to a steady reflux reaction, and maintaining the reflux reaction;

[0024] B6) After the reflux reaction is completed, close the steam valve, open the jacket water inlet valve, and perform cooling crystallization; when the material temperature in the reactor R13002 drops below 35°C, stop cooling;

[0025] B7) Open the discharge valve at the bottom of reactor R13002 and pump the material into the thiadiazole turnover tank V12002 through the discharge pump P13002, open the bottom valve of the turnover tank V12002 and pump the material into the thiadiazole centrifuge M12001 through the turnover pump P12002 for centrifugal drying; perform centrifugal drying; weigh, send samples for analysis, and calculate the yield of thiadiazole; after centrifugation, rinse the reactor R13002 and wait for the next feeding;

[0026] B8) Apply thiadiazole mother liquor, send samples for analysis of HCl content, calculate the amount of hydrochloric acid added and the amount of mother liquor recycled (the thiadiazole mother liquor is pumped from the thiadiazole mother liquor collection tank V12003 to the thiadiazole mother liquor metering tank V13005 via the mother liquor pump P12003, and after metering, it is pumped into the thiadiazole reactor R13002 via the mother liquor transfer pump P13003), and prepare the next batch according to the proportion; replace the mother liquor every 5 to 8 batches of production;

[0027] B9) The ammonium chloride wastewater and centrifugal washing water produced by the thiadiazole cyclization reaction are concentrated into the thiadiazole mother liquor collection tank V12003, and pumped into the wastewater collection tank through the mother liquor pump P12003 for desalination pretreatment and then biochemical treatment.

[0028] Preferably, when the concentrated sulfuric acid in A3) is put into the reactor R13001, the jacket water inlet valve needs to be opened to inject water into the jacket for cooling.

[0029] Preferably, when the hydrazine hydrate solution in A4) is added dropwise, the temperature is maintained at no higher than 60° C. and the dropwise reaction takes about 2 hours to complete.

[0030] Preferably, the acetone in A5) is pumped from the acetone intermediate tank V13006 into the reactor R13001 via the feeding pump P13006, and nitrogen protection is required when adding acetone.

[0031] Preferably, the acetone feed amount accounts for about 0.7% of the feed amount of the dithiourea reactor.

[0032] Preferably, the steady reflux reaction temperature in A7) is 102-107° C., and the reflux reaction is maintained for 4-5 hours.

[0033] Preferably, when the temperature of the material in the cooling crystallization reactor R13001 in A8) drops below 35°C, cooling is stopped.

[0034] Preferably, the steady reflux reaction temperature in B5) is 102-110° C., and the reflux reaction is maintained for about 8-9 hours.

[0035] Compared with the related art, the thiadiazole synthesis process provided by the present invention has the following beneficial effects:

[0036] The present invention provides a thiadiazole synthesis process:

[0037] The present invention manages each step more meticulously as a whole, controls the time and temperature in each step, and adopts an operation mode different from the traditional one, so as to have the advantages of shortening the synthesis reaction time, reducing the reaction temperature, improving the yield, and reducing the by-products. In particular, in the addition of acetone, the acetone does not react with each other in the alkaline solution, nor does it react with sulfuric acid mist, hydrogen chloride, and hydrogen sulfide. Moreover, acetone is easily soluble in water. When the spray tower is used to absorb the acidic waste gas, photocatalytic oxidation + activated carbon adsorption is used to ensure that the exhaust gas meets the standard. DETAILED DESCRIPTION

[0038] The present invention will be further described below in conjunction with the embodiments.

[0039] The thiadiazole synthesis process comprises the following steps:

[0040] Condensation section:

[0041] A1) Before feeding, carefully check whether the dithiourea reactor R13001 and the mixer as well as the water supply, steam supply and power supply are normal, and whether there is any leakage in the valve;

[0042] A2) Pump hydrazine hydrate into hydrazine hydrate metering tank V13003 via feed pump P13005, and pump concentrated sulfuric acid from sulfuric acid storage tank V34301 into concentrated sulfuric acid metering tank V13001 via transfer pump P34301. The metering should be accurate.

[0043] A3) firstly put the water measured by the flow meter into the reactor R13001, and start the stirrer, then open the bottom valve of the concentrated sulfuric acid metering tank V13001 to put the concentrated sulfuric acid into the reactor R13001, and open the jacket water inlet valve to cool it;

[0044] A4) When the temperature in the reactor R13001 is lower than 60°C, open the bottom valve of the hydrazine hydrate metering tank V13003 and slowly add the hydrazine hydrate solution dropwise, keeping the temperature no higher than 60°C. It takes about 2 hours for the reaction to be completed;

[0045] A5) After the addition of hydrazine hydrate is completed, the feed hole of reactor R13001 is opened, and the pre-crushed ammonium thiocyanate is added at one time, and the solid catalyst and acetone with water are added (acetone is pumped into reactor R13001 from acetone intermediate tank V13006 via feed pump P13006, and nitrogen protection is required when adding acetone; because acetone has a low boiling point and is miscible with water, it can effectively reduce the temperature of the reaction system and keep the reflux reaction stable; the acetone feed amount is small (accounting for about 0.7% of the feed amount of the dithiourea reactor), and most of it enters the tail gas purification treatment device through the gas collecting pipe; acetone does not react with each other in alkaline solution, nor does it react with sulfuric acid mist, hydrogen chloride, and hydrogen sulfide, and acetone is easily soluble in water. While using a spray tower to absorb acidic waste gas, photocatalytic oxidation + activated carbon adsorption is used to ensure that the exhaust gas meets the standard) after that, the feed hole is closed and the water inlet valve of condenser E13001 is opened;

[0046] A6) Open the jacket steam valve of reactor R13001 to heat it. When the temperature in reactor R13001 rises to 45-55°C, immediately close the steam valve. Because the system exothermic reaction, it will automatically heat up to a constant value. The reaction time is 1-1.5h.

[0047] A7) After the temperature reaction is completed, turn on the steam to slowly increase the temperature until a stable reflux reaction (temperature 102-107°C) is achieved, and the reflux reaction is maintained for 4-5 hours;

[0048] A8) After the reflux reaction is completed, close the steam valve, open the jacket water inlet valve, and perform cooling crystallization; when the material temperature in the reactor R13001 drops below 35°C, stop cooling;

[0049] A9) Open the discharge valve at the bottom of reactor R13001 and pump the material into dithiourea turnover tank V12001 through the discharge pump P13001, open the bottom valve of turnover tank V12001 and pump the material into dithiourea centrifuge M12002 through the turnover pump P12001 for centrifugal drying; weigh, send samples for analysis, and calculate the yield of dithiourea; after centrifugation, rinse reactor R13001 and wait for the next feeding;

[0050] A10) The ammonium sulfate wastewater and centrifugal washing water produced by the dithiourea condensation reaction are concentrated into the dithiourea mother liquor collection tank V12004, and pumped into the wastewater collection tank through the mother liquor pump P12004 for desalination pretreatment and then biochemical treatment;

[0051] Ring Closing Section:

[0052] B1) Before feeding, carefully check whether the thiadiazole reactor R13002 and the mixer as well as the water, steam and power supply are normal, and whether there is any leakage in the valve;

[0053] B2) Pump hydrochloric acid from the hydrochloric acid storage tank V34302 into the hydrochloric acid metering tank V13004 via the transfer pump P34302. The metering should be accurate.

[0054] B3) firstly put the water measured by the flow meter into the reactor R13002, and start the stirrer, then open the bottom valve of the hydrochloric acid metering tank V13004 to put the hydrochloric acid into the reactor R13002, then put the dithiourea and the solid catalyst into the reactor R13002, and close the feed hole;

[0055] B4) Start the stirrer, open the water inlet valve of condenser E13002, and open the jacket steam valve of reactor R13002 to heat;

[0056] B5) Slowly heat the steam to a steady reflux reaction (temperature 102-110°C), and maintain the reflux reaction for about 8-9 hours;

[0057] B6) After the reflux reaction is completed, close the steam valve, open the jacket water inlet valve, and perform cooling crystallization; when the material temperature in the reactor R13002 drops below 35°C, stop cooling;

[0058] B7) Open the discharge valve at the bottom of reactor R13002 and pump the material into the thiadiazole turnover tank V12002 through the discharge pump P13002, open the bottom valve of the turnover tank V12002 and pump the material into the thiadiazole centrifuge M12001 through the turnover pump P12002 for centrifugal drying; perform centrifugal drying; weigh, send samples for analysis, and calculate the yield of thiadiazole; after centrifugation, rinse the reactor R13002 and wait for the next feeding;

[0059] B8) Apply thiadiazole mother liquor, send samples for analysis of HCl content, calculate the amount of hydrochloric acid added and the amount of mother liquor recycled (the thiadiazole mother liquor is pumped from the thiadiazole mother liquor collection tank V12003 to the thiadiazole mother liquor metering tank V13005 via the mother liquor pump P12003, and after metering, it is pumped into the thiadiazole reactor R13002 via the mother liquor transfer pump P13003), and prepare the next batch according to the proportion; replace the mother liquor every 5 to 8 batches of production;

[0060] B9) The ammonium chloride wastewater and centrifugal washing water produced by the thiadiazole cyclization reaction are concentrated into the thiadiazole mother liquor collection tank V12003, and pumped into the wastewater collection tank through the mother liquor pump P12003 for desalination pretreatment and then biochemical treatment.

[0061] Compared with the related art, the thiadiazole synthesis process provided by the present invention has the following beneficial effects:

[0062] The invention provides a thiadiazole synthesis process. By performing relatively refined management on each step as a whole, the time and temperature in each step are controlled, and an operation mode different from the traditional one is adopted, so that the synthesis reaction time is shortened, the reaction temperature is reduced, the yield is improved, and the by-products are reduced. In particular, in the addition of acetone, the acetone does not react with each other in an alkaline solution, and does not react with sulfuric acid mist, hydrogen chloride, and hydrogen sulfide. Moreover, the acetone is easily soluble in water. When a spray tower is used to absorb acidic waste gas, photocatalytic oxidation + activated carbon adsorption is used to ensure that the exhaust gas meets the standard.

[0063] The above descriptions are merely embodiments of the present invention and are not intended to limit the patent scope of the present invention. Any equivalent structure or equivalent process transformation made using the contents of the present invention specification, or directly or indirectly applied in other related technical fields, are also included in the patent protection scope of the present invention.

Claims

1. A thiadiazole synthesis process, characterized in that: The following steps are involved: Condensation section: A1) Before feeding, carefully check whether the dithiourea reactor R13001 and the mixer as well as the water supply, steam supply and power supply are normal, and whether there is any leakage in the valve; A2) Pump hydrazine hydrate into hydrazine hydrate metering tank V13003 via feed pump P13005, and pump concentrated sulfuric acid from sulfuric acid storage tank V34301 into concentrated sulfuric acid metering tank V13001 via transfer pump P34301. The metering should be accurate. A3) First, water measured by a flow meter is put into the reactor R13001, and the stirrer is turned on, and then the bottom valve of the concentrated sulfuric acid metering tank V13001 is opened to put the concentrated sulfuric acid into the reactor R13001; A4) When the temperature in the reactor R13001 is lower than 60°C, open the bottom valve of the hydrazine hydrate metering tank V13003 and slowly add the hydrazine hydrate solution; A5) After the addition of hydrazine hydrate is completed, the feed hole of reactor R13001 is opened, the pre-crushed ammonium thiocyanate is added at one time, and after the solid catalyst and the water-carrying acetone are added, the feed hole is closed and the water inlet valve of condenser E13001 is opened; A6) Open the jacket steam valve of reactor R13001 and heat it. When the temperature in reactor R13001 rises to 45-55°C, immediately close the steam valve. The reaction time is 1-1.5h. A7) After the temperature reaction is completed, the steam is turned on to slowly increase the temperature until a steady reflux reaction occurs, and the reflux reaction is maintained; A8) After the reflux reaction is completed, the steam valve is closed, and the jacket water inlet valve is opened to perform cooling crystallization; A9) Open the discharge valve at the bottom of reactor R13001 and pump the material into dithiourea turnover tank V12001 through the discharge pump P13001, open the bottom valve of turnover tank V12001 and pump the material into dithiourea centrifuge M12002 through the turnover pump P12001 for centrifugal drying; weigh, send samples for analysis, and calculate the yield of dithiourea; after centrifugation, rinse reactor R13001 and wait for the next feeding; A10) The ammonium sulfate wastewater and centrifugal washing water produced by the dithiourea condensation reaction are concentrated into the dithiourea mother liquor collection tank V12004, and pumped into the wastewater collection tank through the mother liquor pump P12004 for desalination pretreatment and then biochemical treatment; Ring Closing Section: B1) Before feeding, carefully check whether the thiadiazole reactor R13002 and the mixer as well as the water, steam and power supply are normal, and whether there is any leakage in the valve; B2) Pump hydrochloric acid from the hydrochloric acid storage tank V34302 into the hydrochloric acid metering tank V13004 via the transfer pump P34302. The metering should be accurate. B3) firstly put the water measured by the flow meter into the reactor R13002, and start the stirrer, then open the bottom valve of the hydrochloric acid metering tank V13004 to put the hydrochloric acid into the reactor R13002, then put the dithiourea and the solid catalyst into the reactor R13002, and close the feed hole; B4) Start the stirrer, open the water inlet valve of condenser E13002, and open the jacket steam valve of reactor R13002 to heat; B5) Slowly heating the steam to a steady reflux reaction, and maintaining the reflux reaction; B6) After the reflux reaction is completed, close the steam valve, open the jacket water inlet valve, and perform cooling crystallization; when the material temperature in the reactor R13002 drops below 35°C, stop cooling; B7) Open the discharge valve at the bottom of reactor R13002 and pump the material into the thiadiazole turnover tank V12002 through the discharge pump P13002, open the bottom valve of the turnover tank V12002 and pump the material into the thiadiazole centrifuge M12001 through the turnover pump P12002 for centrifugal drying; perform centrifugal drying; weigh, send samples for analysis, and calculate the yield of thiadiazole; after centrifugation, rinse the reactor R13002 and wait for the next feeding; B8) Apply thiadiazole mother liquor, send samples for analysis of HCl content, calculate the amount of hydrochloric acid added and the amount of mother liquor recycled (the thiadiazole mother liquor is pumped from the thiadiazole mother liquor collection tank V12003 to the thiadiazole mother liquor metering tank V13005 via the mother liquor pump P12003, and after metering, it is pumped into the thiadiazole reactor R13002 via the mother liquor transfer pump P13003), and prepare the next batch according to the proportion; replace the mother liquor every 5 to 8 batches of production; B9) The ammonium chloride wastewater and centrifugal washing water produced by the thiadiazole cyclization reaction are concentrated into the thiadiazole mother liquor collection tank V12003, and pumped into the wastewater collection tank through the mother liquor pump P12003 for desalination pretreatment and then biochemical treatment.

2. The thiadiazole synthesis process according to claim 1, characterized in that: When the concentrated sulfuric acid in A3) is put into the reactor R13001, the jacket water inlet valve needs to be opened to inject water into the jacket for cooling.

3. The thiadiazole synthesis process according to claim 1, characterized in that: When the hydrazine hydrate solution in A4) is added dropwise, the temperature is maintained at no higher than 60° C. The dropwise reaction takes about 2 hours to complete.

4. The thiadiazole synthesis process according to claim 1, characterized in that: The acetone in A5) is pumped into the reactor R13001 from the acetone intermediate tank V13006 via the feeding pump P13006, and nitrogen protection is required when adding acetone.

5. The thiadiazole synthesis process according to claim 1 or 4, characterized in that: The acetone feed amount accounts for about 0.7% of the feed amount of the dithiourea reactor.

6. The thiadiazole synthesis process according to claim 1, characterized in that: The steady reflux reaction temperature in A7) is 102-107° C., and the reflux reaction is maintained for 4-5 hours.

7. The thiadiazole synthesis process according to claim 1, characterized in that: When the temperature of the material in the cooling crystallization reactor R13001 in A8) drops below 35°C, cooling is stopped.

8. The thiadiazole synthesis process according to claim 1, characterized in that: The steady reflux reaction temperature in B5) is 102-110° C., and the reflux reaction is maintained for about 8-9 hours.