CN110773088B - Microreactor and method for continuously synthesizing sancycline by using same - Google Patents
Microreactor and method for continuously synthesizing sancycline by using same Download PDFInfo
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- CN110773088B CN110773088B CN201910984208.4A CN201910984208A CN110773088B CN 110773088 B CN110773088 B CN 110773088B CN 201910984208 A CN201910984208 A CN 201910984208A CN 110773088 B CN110773088 B CN 110773088B
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0093—Microreactors, e.g. miniaturised or microfabricated reactors
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F27/00—Mixers with rotary stirring devices in fixed receptacles; Kneaders
- B01F27/60—Mixers with rotary stirring devices in fixed receptacles; Kneaders with stirrers rotating about a horizontal or inclined axis
- B01F27/70—Mixers with rotary stirring devices in fixed receptacles; Kneaders with stirrers rotating about a horizontal or inclined axis with paddles, blades or arms
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F27/00—Mixers with rotary stirring devices in fixed receptacles; Kneaders
- B01F27/80—Mixers with rotary stirring devices in fixed receptacles; Kneaders with stirrers rotating about a substantially vertical axis
- B01F27/90—Mixers with rotary stirring devices in fixed receptacles; Kneaders with stirrers rotating about a substantially vertical axis with paddles or arms
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0053—Details of the reactor
- B01J19/006—Baffles
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/18—Stationary reactors having moving elements inside
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/22—Separation; Purification; Stabilisation; Use of additives
- C07C231/24—Separation; Purification
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/40—Ortho- or ortho- and peri-condensed systems containing four condensed rings
- C07C2603/42—Ortho- or ortho- and peri-condensed systems containing four condensed rings containing only six-membered rings
- C07C2603/44—Naphthacenes; Hydrogenated naphthacenes
- C07C2603/46—1,4,4a,5,5a,6,11,12a- Octahydronaphthacenes, e.g. tetracyclines
Abstract
The invention discloses a micro-reactor, which comprises two micro-reactors and a stirring box, wherein a first stirring device is arranged in the stirring box, the lower end of the stirring box is connected with a first liquid outlet pipe, one end of the first liquid outlet pipe is connected with a first booster pump, the lower ends of the two micro-reactors are both connected with second liquid outlet pipes, one end of one second liquid outlet pipe is connected with a second booster pump, one ends of the first booster pump and the second booster pump are both connected with a liquid conveying pipe, and the upper ends of the two micro-reactors are both connected with a connecting box; the invention also provides a method for continuously synthesizing the sancycline by the microreactor. The whole synthesis process has the characteristics of continuity, high production efficiency, short production period, energy conservation, environmental protection, less side reaction, good product quality, low production cost and the like, and in addition, the pipelining device is simple, the investment is low, the process safety is good, the reaction condition is easy to control, and the synthesis process has great industrialization prospect.
Description
Technical Field
The invention relates to the technical field of sancycline, in particular to a microreactor and a method for continuously synthesizing the sancycline by using the microreactor.
Background
Sancycline, also known as desmethyldeoxytetracycline, is an important intermediate in the synthesis of minocycline. The industrialized sancycline synthesis technology at present is mainly prepared by taking demethyl aureomycin as a raw material through dechlorination and dehydroxylation.
In the US2999111, demethylated aureomycin is used as a raw material, methanol is used as a solvent, and 5% Pd/C is used for catalytic hydrogenation to directly obtain the sancycline, so that the yield can reach 30%. The technical disadvantages are low yield and poor product purity.
US patent No. 3160661 uses demethyltetracycline as raw material, DMF-hydrobromic acid as solvent, 5% Pd/C catalytic hydrogenation, the product is sancycline, yield: 80 percent. The technical disadvantages are that the raw materials are not easy to obtain and the cost is high.
The literature (journal of Chinese medical industry, 2008, 325-containing 327) reports that demethylated aureomycin is reduced by 5% Pd/C high-pressure catalytic hydrogenation under alkaline condition to obtain demethylated tetracycline, and then the yagecycline is reduced by 5% Pd/C high-pressure catalytic hydrogenation under acidic condition to obtain the yield of 54% in two steps. The technical defects are low yield, two steps and complicated operation.
DE2232900 uses demethylated aureomycin as raw material, formic acid as solvent, and 5% Rh/C for catalytic hydrogenation to obtain sancycline directly, with a yield of 70%. The technical defects are low yield and difficult post-treatment purification.
CN103387511B takes demethylated aureomycin as raw material, alcohol and acid as mixed solvent, Rh/C is catalyzed and hydrogenated to directly obtain the sancycline solution, and the sancycline solution is purified by macroporous absorption resin and frozen and crystallized to obtain the sancycline finished product, which can reach the yield of 85 percent. The technical defects are that the back extraction is complicated, the cost is high and the yield is low.
The catalytic hydrogenation stages of the methods all adopt a traditional batch kettle type production process, the production period is long, the hydrogen consumption is high, a large amount of organic solvents are needed, the large-scale and continuous production of the process is not facilitated, the hydrogenation reaction pressure is too high, and potential safety hazards are easily caused.
Disclosure of Invention
The invention aims to solve the defects in the prior art and provides a microreactor and a method for continuously synthesizing sancycline by using the microreactor.
In order to achieve the purpose, the invention adopts the following technical scheme:
a micro-reactor comprises two micro-reactors and a stirring box, wherein a first stirring device is arranged in the stirring box, the lower end of the stirring box is connected with a first liquid outlet pipe, one end of the first liquid outlet pipe is connected with a first booster pump, the lower ends of the two micro-reactors are both connected with a second liquid outlet pipe, one end of one second liquid outlet pipe is connected with a second booster pump, one ends of the first booster pump and the second booster pump are both connected with liquid conveying pipes, the upper ends of the two micro-reactors are both connected with a connecting box, the upper ends of the two liquid conveying pipes are respectively connected with one side of the two connecting boxes, one side of the connecting box is fixedly provided with a gas distributor through a connecting piece, one side of the lower end of the gas distributor is connected with a gas conveying pipe, one ends of the two gas conveying pipes are respectively connected with one side of the two connecting boxes, a second stirring device is arranged in the micro-reactors, four fixing rods are arranged at equal intervals around the micro-reactors, two dead levers with one side are a set of, and the one side of two dead levers can be dismantled jointly and be connected with the mounting panel in same a set of, is fixed with the backup pad jointly between two mounting panels, is fixed with the fixed plate jointly between four dead levers, be equipped with the opening on the fixed plate, the lower extreme of microreactor runs through the lateral wall of opening and backup pad and extends to the lower extreme of backup pad.
Preferably, the first stirring device comprises a first stirring rod and a second stirring rod which are respectively arranged at two sides of the stirring box in a penetrating way, a second motor mounting seat is fixed at the upper end of the stirring box, a second driving motor is fixed on the second motor mounting seat, the output shaft of the second driving motor is connected with the upper end of the first stirring rod through a second coupling, a fixed block is fixed on one side of the stirring box, a third motor mounting seat is fixed on one side of the fixed block, a third driving motor is arranged on the third motor mounting seat, an output shaft of the third driving motor is connected with one end of the second stirring rod through a third coupling, and the second puddler runs through the fixed block, a week equidistant of first puddler is fixed with two above first stirring leaves, a week equidistant of second puddler is fixed with two above second stirring leaves.
Preferably, the second agitating unit is including running through two third puddlers that set up in two microreactors and two connection box upper ends respectively, the upper end of connection box is fixed with first motor mount pad through the mounting, be fixed with first driving motor on the first motor mount pad, first driving motor's output shaft passes through the upper end of first coupling joint at the third puddler, a week equidistant third stirring leaf more than two that is fixed with of third puddler.
Preferably, four through holes are formed in the two mounting plates, two thread blind holes corresponding to the through holes are formed in one side of each fixing rod, screws penetrate through the through holes, and one ends of the screws extend into the thread blind holes.
Preferably, the upper end one side of fixed plate and agitator tank is fixed with the bracing piece, the upper end of bracing piece is fixed with the control box, one side of fixed plate is fixed with solid fixed ring, gu fixed ring runs through the setting on the transfer line, one side of agitator tank is connected with the inlet pipe, the lower extreme four corners of agitator tank all is fixed with the carrier bar, all be equipped with the valve on first drain pipe and the transfer line, the lower extreme of first booster pump is fixed with the plummer, the lower extreme of dead lever is fixed with the supporting seat.
The invention also provides a method for continuously synthesizing the sancycline by the microreactor, which comprises the following steps:
s1, dissolving the demethylated aureomycin in an organic solvent, uniformly stirring, and adjusting the pH value to 7.0-9.0 by an alkaline substance;
s2, inputting the obtained mixture containing the demethylated aureomycin into one of the microreactors loaded with hydrogenation catalysts through a first booster pump, continuously introducing hydrogen through a gas distributor for catalytic hydrogenation, and controlling the reaction temperature and the residence time to obtain a mixture of the demethylated tetracycline and the organic solvent;
s3, adjusting the pH of the mixture passing through S2 to 1.0-5.0 by using an acidic substance, inputting the mixture into the other microreactor loaded with a hydrogenation catalyst through a second booster pump, continuously introducing hydrogen through a gas distributor for catalytic hydrogenation, and controlling the reaction temperature and the residence time to obtain a mixture of the sancycline and the organic solvent;
and S4, adjusting and crystallizing the sancycline solution, and drying by using a blast dryer to obtain a finished sancycline product.
Preferably, in S1, the organic solvent is methanol, ethanol or isopropanol, and the basic substance is sodium hydroxide, triethylamine or ammonia water.
Preferably, in S2, the hydrogenation catalyst is 20-100 mesh Pd-C, Rh-C or Raney-Ni catalyst, the reaction temperature is 40-75 deg.C, the pressure of the reaction system is 0.5-1.0MPa, and the retention time is 100-300S.
Preferably, in the S3, the reaction temperature is 30-60 ℃, the pressure of the reaction system is 0.5-1.0MPa, and the residence time is 300-900S.
Preferably, in the S4, the crystallization end point is pH0-1.0, and the forced air drying temperature is 60-80 ℃.
The invention has the beneficial effects that:
1. the demethylated aureomycin is used as a raw material, the raw material is simple and easy to obtain, the cost is saved, meanwhile, the post-treatment is simple and effective, and the cost is low;
2. the invention greatly reduces the consumption of hydrogen and catalyst, reduces the cost and simultaneously greatly improves the safety coefficient of hydrogenation reaction;
in conclusion, the whole synthesis process has the characteristics of continuity, high production efficiency, short production period, energy conservation, environmental protection, less side reaction, good product quality, low production cost and the like, and in addition, the pipelining device is simple, the investment is low, the process safety is good, the reaction conditions are easy to control, and the synthesis process has great industrial prospect.
Drawings
FIG. 1 is a schematic structural diagram of a microreactor according to the present invention;
FIG. 2 is a schematic structural diagram of a first stirring device of a microreactor according to the present invention;
FIG. 3 is an enlarged view of a microreactor according to the present invention at A;
fig. 4 is an enlarged view of a microreactor according to the present invention at B.
In the figure: 1 a first motor mounting seat, 2 a first driving motor, 3 a connecting box, 4 supporting rods, 5 infusion tubes, 6 fixing rings, 7 a second motor mounting seat, 8 a second driving motor, 9 a second coupler, 10 a feeding pipe, 11 a stirring box, 12 a bearing rod, 13 a first liquid outlet pipe, 14 valves, 15 bearing tables, 16 a supporting seat, 17 a first booster pump, 18 a supporting plate, 19 a second liquid outlet pipe, 20 a mounting plate, 21 a micro-reactor, 22 a fixing plate, 23 a fixing rod, 24 a gas conveying pipe, 25 a fixing part, 26 a first coupler, 27 a gas distributor, 28 a first stirring blade, 29 a first stirring rod, 30 a second stirring blade, 31 a second stirring rod, 32 a third driving motor, 33 a third motor mounting seat, 34 a third coupler, 35 a fixing block, 36 a second booster pump, 37 screws and 38 a control box.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments.
Referring to fig. 1-4, a micro-reactor comprises two micro-reactors 21 and a stirring tank 11, a first stirring device is arranged in the stirring tank 11, so as to stir an organic solvent dissolved with aureomycin, a first liquid outlet pipe 13 is connected to the lower end of the stirring tank 11, one end of the first liquid outlet pipe 13 is connected with a first booster pump 17, and a mixture after stirring is conveniently conveyed into one of the micro-reactors 21 under the action of the first booster pump 17.
In the invention, the lower ends of two micro reactors 21 are both connected with second liquid outlet pipes 19, one end of one of the second liquid outlet pipes 19 is connected with a second booster pump 36, one ends of a first booster pump 17 and the second booster pump 36 are both connected with a liquid conveying pipe 5, the liquid conveying pipe 5 is used for conveniently conveying mixed solution, the upper ends of the two micro reactors 21 are both connected with connecting boxes 3, the upper ends of the two liquid conveying pipes 5 are respectively connected to one sides of the two connecting boxes 3, one side of each connecting box 3 is fixed with a gas distributor 27 through a connecting piece, and under the action of the gas distributor 27, hydrogen is conveniently introduced for catalytic hydrogenation.
In the invention, one side of the lower end of the gas distributor 27 is connected with the gas transmission pipe 24, one end of each of the two gas transmission pipes 24 is respectively connected with one side of each of the two connecting boxes 3, gas is transmitted into the microreactor 21 through the gas transmission pipe 24, and the second stirring device is arranged in the microreactor 21, so that the mixture can be conveniently stirred again, the mixture can be fully reacted, and the reaction speed is increased.
In the invention, four fixing rods 23 are arranged at equal intervals around the microreactor 21, two fixing rods 23 on the same side form a group, one sides of the two fixing rods 23 in the same group are jointly detachably connected with mounting plates 20, a supporting plate 18 is jointly fixed between the two mounting plates 20, the firmness between the fixing rods 23 is conveniently improved by using the supporting plate 18, fixing plates 22 are jointly fixed between the four fixing rods 23, openings are arranged on the fixing plates 22, the lower end of the microreactor 21 penetrates through the openings and the side wall of the supporting plate 18 and extends to the lower end of the supporting plate 18, and the fixing plates 22 are used for conveniently supporting and limiting the microreactor 21.
In the invention, the first stirring device comprises a first stirring rod 29 and a second stirring rod 31 which are respectively arranged on two sides of the stirring box 11 in a penetrating mode, a second motor mounting seat 7 is fixed at the upper end of the stirring box 11, a second driving motor 8 is fixed on the second motor mounting seat 7, the second driving motor 8 is connected with an external component, stable operation of the stirring device is facilitated, and operation and control of workers are facilitated, an output shaft of the second driving motor 8 is connected to the upper end of the first stirring rod 29 through a second coupler 9, and an output shaft of the second driving motor 8 rotates to drive the first stirring rod 29 to rotate.
In the invention, a fixed block 35 is fixed on one side of the stirring box 11 to play a supporting role, a third motor mounting seat 33 is fixed on one side of the fixed block 35, a third driving motor 32 is mounted on the third motor mounting seat 33, the third driving motor 32 is connected with an external component to facilitate stable operation of the third driving motor, and is convenient for a worker to control, an output shaft of the third driving motor 32 is connected to one end of a second stirring rod 31 through a third coupler 34, the second stirring rod 31 penetrates through the fixed block 35, more than two first stirring blades 28 are fixed on one circle of the first stirring rod 29 at equal intervals, more than two second stirring blades 30 are fixed on one circle of the second stirring rod 31 at equal intervals, and an output shaft of the third driving motor 32 rotates to drive the second stirring rod 31 to rotate so as to drive the second stirring blades 30 to rotate, thereby facilitating full stirring of a mixed solution.
In the invention, the second stirring device comprises two third stirring rods which are respectively arranged at the upper ends of the two micro reactors 21 and the two connecting boxes 3 in a penetrating manner, the upper end of the connecting box 3 is fixedly provided with a first motor mounting seat 1 through a fixing piece 25, a first driving motor 2 is fixedly arranged on the first motor mounting seat 1, an output shaft of the first driving motor 2 is connected to the upper end of the third stirring rod through a first coupling 26, more than two third stirring blades are equidistantly fixed on the periphery of the third stirring rod, the first driving motor 2 is connected with an external part to facilitate the stable operation of the first driving motor, and a worker can conveniently control the first stirring rod through the rotation of the output shaft of the first driving motor 2, so that the third stirring blades are driven to rotate, and the reaction speed of a mixed solution is facilitated to be accelerated.
In the invention, four through holes are arranged on two mounting plates 20, two thread blind holes corresponding to the through holes are arranged on one sides of four fixing rods 23, screws 37 penetrate through the through holes, one ends of the screws 37 extend into the thread blind holes, the mounting plates 20 are conveniently and firmly fixed on the fixing rods 23 by the screws 37, and the strength is improved.
In the invention, a support rod 4 is fixed on one side of the upper ends of a fixed plate 22 and an agitating tank 11, a control box 38 is fixed on the upper end of the support rod 4 to control temperature and time conveniently, a fixing ring 6 is fixed on one side of the fixed plate 22, the fixing ring 6 is arranged on an infusion tube 5 in a penetrating manner to limit the infusion tube 5 conveniently, an inlet tube 10 is connected to one side of the agitating tank 11 to add raw materials conveniently, bearing rods 12 are fixed on four corners of the lower end of the agitating tank 11 to play a supporting role, valves 14 are arranged on a first liquid outlet tube 13 and the infusion tube 5, a bearing platform 15 is fixed on the lower end of a first booster pump 17, and a supporting seat 16 is fixed on the lower end of a fixing rod 23 to play a role in stable supporting.
The invention also provides a method for continuously synthesizing the sancycline by the microreactor, which comprises the following steps:
s1, dissolving the demethylated aureomycin in an organic solvent, uniformly stirring, adjusting the pH value of an alkaline substance to 7.0-9.0, wherein the organic solvent is methanol, ethanol or isopropanol, and the alkaline substance is sodium hydroxide, triethylamine or ammonia water;
s2, inputting the obtained mixture containing the demethylated aureomycin into one of the microreactors 21 loaded with hydrogenation catalysts through a first booster pump 17, simultaneously continuously introducing hydrogen through a gas distributor 27 for catalytic hydrogenation, controlling the reaction temperature and the residence time to obtain a mixture of demethylated tetracycline and an organic solvent, wherein the hydrogenation catalysts are 20-100 meshes of palladium carbon, rhodium carbon or Raney nickel catalysts, the reaction temperature is 40-75 ℃, the pressure of a reaction system is 0.5-1.0MPa, and the residence time is 100-300S;
s3, adjusting the pH of the mixture passing through S2 to 1.0-5.0 by using an acidic substance, inputting the mixture into the other microreactor 21 loaded with a hydrogenation catalyst through a second booster pump 36, continuously introducing hydrogen through a gas distributor 27 for catalytic hydrogenation, and controlling the reaction temperature and the residence time to obtain a mixture of the sancycline and the organic solvent, wherein the reaction temperature is 30-60 ℃, the pressure of the reaction system is 0.5-1.0MPa, and the residence time is 300-900S;
s4, adjusting the temperature of the solution of the sancycline to crystallize, and drying the solution of the sancycline by an air blast dryer to obtain a finished product of the sancycline, wherein the crystallization end point is pH0-1.0, and the air blast drying temperature is 60-80 ℃.
In the invention, when in use, 50g of demethylated aureomycin and 210ml of methanol are added into a stirring box 11 through a feeding pipe 10, then an output shaft of a second driving motor 8 rotates to drive a first stirring rod 29 to rotate, the first stirring rod 29 rotates to drive a first stirring blade 28 to rotate, an output shaft of a third driving motor 32 rotates to drive a second stirring rod 31 to rotate, the second stirring rod 31 drives a second stirring blade 30 to rotate so as to be fully and uniformly mixed, simultaneously, the pH value of sodium hydroxide is adjusted to 8.70, the mixture is input into one micro-reactor 21 loaded with 60-mesh rhodium carbon catalyst through a first booster pump 17, hydrogen is continuously introduced through a gas distributor 27 for catalytic hydrogenation, the reaction temperature is 72 ℃, the reaction pressure is 0.9MPa, the retention time is 150s, after the catalytic dechlorination hydrogenation reaction is finished, the pH value of the reaction liquid is adjusted to 0.9 by concentrated sulfuric acid, the mixture is input into the other micro-reactor 21 loaded with 60-mesh rhodium carbon catalyst through a second booster pump 36, meanwhile, hydrogen is continuously introduced through a gas distributor 27 for catalytic hydrogenation, an output shaft of a first driving motor 2 is used for driving a third stirring rod to rotate, a third stirring blade is driven to rotate to accelerate catalytic hydrogenation, the reaction temperature of the other microreactor is 55 ℃, the reaction pressure is 0.8MPa, the residence time is 500s, after the catalytic dehydroxylation hydrogenation reaction is finished, reaction liquid is filtered, the pH value of concentrated hydrochloric acid is adjusted to 0.4, crystal growth is carried out at room temperature for 2h, then suction filtration is carried out, 30mL of methanol is used for washing filter cakes, the temperature is adjusted to 60 ℃, and then air blowing and drying are carried out until the constant weight are achieved, so that the product of the sancycline is obtained.
The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art should be considered to be within the technical scope of the present invention, and the technical solutions and the inventive concepts thereof according to the present invention should be equivalent or changed within the scope of the present invention.
Claims (8)
1. A method for continuously synthesizing sancycline by a microreactor comprises two microreactors (21) and a stirring box (11), and is characterized in that: the stirring device is characterized in that a first stirring device is arranged in the stirring box (11), the lower end of the stirring box (11) is connected with a first liquid outlet pipe (13), one end of the first liquid outlet pipe (13) is connected with a first booster pump (17), the lower ends of the two micro reactors (21) are connected with a second liquid outlet pipe (19), one end of one second liquid outlet pipe (19) is connected with a second booster pump (36), one ends of the first booster pump (17) and the second booster pump (36) are connected with a liquid conveying pipe (5), the upper ends of the two micro reactors (21) are connected with a connecting box (3), the upper ends of the two liquid conveying pipes (5) are respectively connected to one side of the two connecting boxes (3), one side of each connecting box (3) is fixed with a gas distributor (27) through a connecting piece, one side of the lower end of each gas distributor gas conveying pipe (27) is connected with a connecting box (24), one ends of the two gas conveying pipes (24) are respectively connected to one side of each connecting box (3), a second stirring device is arranged in the microreactor (21), four fixing rods (23) are arranged in the microreactor (21) at equal intervals in a circle, two fixing rods (23) on the same side are in a group, one sides of the two fixing rods (23) in the same group are detachably connected with mounting plates (20) together, a supporting plate (18) is fixed between the two mounting plates (20) together, a fixing plate (22) is fixed between the four fixing rods (23) together, an opening is formed in the fixing plate (22), and the lower end of the microreactor (21) penetrates through the opening and the side wall of the supporting plate (18) and extends to the lower end of the supporting plate (18);
the second stirring device comprises two third stirring rods which are respectively arranged at the upper ends of the two micro reactors (21) and the two connecting boxes (3) in a penetrating mode, a first motor mounting seat (1) is fixed at the upper end of each connecting box (3) through a fixing piece (25), a first driving motor (2) is fixed on each first motor mounting seat (1), an output shaft of each first driving motor (2) is connected to the upper end of each third stirring rod through a first coupler (26), and more than two third stirring blades are fixed on the third stirring rods at equal intervals in a circle;
a method of synthesizing a sancycline, comprising the steps of:
s1, dissolving the demethylated aureomycin in an organic solvent, uniformly stirring, and adjusting the pH value to 7.0-9.0 by an alkaline substance;
s2, inputting the obtained mixture containing the demethylated aureomycin into one of the microreactors (21) loaded with hydrogenation catalysts through a first booster pump (17), simultaneously continuously introducing hydrogen through a gas distributor (27) for catalytic hydrogenation, and controlling the reaction temperature and the residence time to obtain a mixture of demethylated tetracycline and an organic solvent;
s3, adjusting the pH of the mixture passing through S2 to 1.0-5.0 by using an acidic substance, inputting the mixture into another microreactor (21) loaded with a hydrogenation catalyst through a second booster pump (36), continuously introducing hydrogen through a gas distributor (27) to perform catalytic hydrogenation, and controlling the reaction temperature and the residence time to obtain a mixture of the sancycline and the organic solvent;
and S4, adjusting and crystallizing the sancycline solution, and drying by using a blast dryer to obtain a finished sancycline product.
2. The method for continuously synthesizing the sancycline by the microreactor according to claim 1, characterized in that: the first stirring device comprises a first stirring rod (29) and a second stirring rod (31) which are respectively arranged on two sides of a stirring box (11) in a penetrating mode, a second motor mounting seat (7) is fixed at the upper end of the stirring box (11), a second driving motor (8) is fixed on the second motor mounting seat (7), an output shaft of the second driving motor (8) is connected to the upper end of the first stirring rod (29) through a second coupler (9), a fixing block (35) is fixed on one side of the stirring box (11), a third motor mounting seat (33) is fixed on one side of the fixing block (35), a third driving motor (32) is installed on the third motor mounting seat (33), an output shaft of the third driving motor (32) is connected to one end of the second stirring rod (31) through a third coupler (34), and the second stirring rod (31) penetrates through the fixing block (35), more than two first stirring blades (28) are fixed on the first stirring rod (29) at equal intervals in a circle, and more than two second stirring blades (30) are fixed on the second stirring rod (31) at equal intervals in a circle.
3. The method for continuously synthesizing the sancycline by the microreactor according to claim 1, characterized in that: be equipped with four through-holes on two mounting panels (20), one side of four dead levers (23) all is equipped with two screw thread blind holes that correspond with the through-hole, run through in the through-hole and be equipped with screw (37), the one end of screw (37) extends to in the screw thread blind hole.
4. The method for continuously synthesizing the sancycline by the microreactor according to claim 1, characterized in that: the utility model discloses a support device for infusion pump, including fixed plate (22), agitator tank (11), upper end one side of fixed plate (22) and agitator tank (11) is fixed with bracing piece (4), the upper end of bracing piece (4) is fixed with control box (38), one side of fixed plate (22) is fixed with solid fixed ring (6), gu fixed ring (6) run through the setting on transfer line (5), one side of agitator tank (11) is connected with inlet pipe (10), the lower extreme four corners of agitator tank (11) all is fixed with carrier bar (12), all be equipped with valve (14) on first drain pipe (13) and transfer line (5), the lower extreme of first booster pump (17) is fixed with plummer (15), the lower extreme of dead lever (23) is fixed with supporting seat (16).
5. The method for continuously synthesizing the sancycline by the microreactor according to claim 1, characterized in that: in the S1, the organic solvent is methanol, ethanol or isopropanol, and the alkaline substance is sodium hydroxide, triethylamine or ammonia water.
6. The method for continuously synthesizing the sancycline by the microreactor according to claim 1, characterized in that: in the S2, the hydrogenation catalyst is 20-100 mesh Pd-C, Rh-C or Raney-Ni catalyst, the reaction temperature is 40-75 ℃, the pressure of the reaction system is 0.5-1.0MPa, and the retention time is 100-300S.
7. The method for continuously synthesizing the sancycline by the microreactor according to claim 1, characterized in that: in the S3, the reaction temperature is 30-60 ℃, the pressure of the reaction system is 0.5-1.0MPa, and the retention time is 300-900S.
8. The method for continuously synthesizing the sancycline by the microreactor according to claim 1, characterized in that: in the S4, the crystallization end point is pH0-1.0, and the forced air drying temperature is 60-80 ℃.
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