CN111362891A - Production device and production method of acetyl tetrahydrofuran - Google Patents
Production device and production method of acetyl tetrahydrofuran Download PDFInfo
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- CN111362891A CN111362891A CN202010250879.0A CN202010250879A CN111362891A CN 111362891 A CN111362891 A CN 111362891A CN 202010250879 A CN202010250879 A CN 202010250879A CN 111362891 A CN111362891 A CN 111362891A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B57/00—Separation of optically-active compounds
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- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
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- 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
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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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- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D307/10—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D307/18—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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Abstract
The invention discloses a production device and a production method of acetyltetrahydrofuran, and aims to provide a production device and a production method of acetyltetrahydrofuran, which are low in production cost and high in reaction yield. The improved box comprises a box body, the inside box cavity that is equipped with of box, from the top down is fixed with cavity one, cavity two and cavity three in the box cavity respectively, the up end of cavity one is fixed with charge door one and charge door two respectively, the bottom of cavity one is equipped with discharge gate one, install the discharge gate subassembly in the discharge gate one, pan feeding mouth one and liquid supply subassembly one are installed respectively to the up end of cavity two, the bottom of cavity two is equipped with discharge gate two, the up end of cavity three is installed respectively and is supplied liquid subassembly two, liquid supply subassembly three and with discharge gate two phase assorted pan feeding mouth two, the bottom of cavity three is equipped with discharge gate three. The invention has the beneficial effects that: the reaction yield is high; the production cost is low; the reaction rate is fast.
Description
Technical Field
The invention relates to the related technical field of medical intermediates, in particular to a production device and a production method of acetyl tetrahydrofuran.
Background
Acetyl tetrahydrofuran, chemical name 1- [ (2S) -tetrahydro-2-furyl ] ethanone, is a key intermediate for synthesizing antibacterial agent cefacin and novel carbapenem.
The currently reported synthetic route: the method comprises the following steps: in the patent US2003-114693A, S-tetrahydrofuran carbonitrile is used as a raw material, and a Grignard reaction is performed on the S-tetrahydrofuran carbonitrile and methyl magnesium chloride to prepare a target product. The method has short route and high yield, but the raw material S-tetrahydrofuran formonitrile is difficult to purchase in a large scale and is expensive, so that the method is not suitable for industrial mass production. And a second route: the method comprises the steps of taking S-tetrahydrofuran formic acid as an initial material, reacting with thionyl chloride and methanol to generate methyl ester, then reacting with ammonia gas to form amide, performing dehydration reaction to form S-tetrahydrofuran formonitrile, and finally performing Grignard reaction with methyl magnesium chloride to obtain a target product. The method has the advantages of long reaction route, low total reaction yield, high production cost and no market competitiveness of price. And a third route: s-tetrahydrofuran formic acid is used as a starting material, an active intermediate is formed with carbonyl diimidazole, and then isopropyl malonate is added for condensation reaction to form a condensation compound. The condensate is hydrolyzed and decarboxylated to form the target product. The route can realize industrial production, but the decarboxylation process of the condensation compound needs higher temperature, more side reactions can occur, the product needs rectification and purification, and partial racemization occurs in the purification process, so that the ee value is reduced.
The current industrialized synthetic route basically takes S-tetrahydrofuran formic acid as a starting material. S-tetrahydrofuran carboxylic acid is a key intermediate for synthesizing a plurality of chiral drugs. At present, optically pure tetrahydrofuran formic acid is mainly obtained in a resolution mode, salt obtained by resolution needs to be separated by hydrochloric acid, but the tetrahydrofuran formic acid has high water solubility and poor extraction effect by solvent extraction, so that the resolution yield is low.
Disclosure of Invention
The invention provides a production device and a production method of acetyltetrahydrofuran, which are used for overcoming the defects of high production cost and low reaction yield in the prior art and have low production cost and high reaction yield.
In order to achieve the purpose, the invention adopts the following technical scheme:
a method for producing acetyltetrahydrofuran, comprising the steps of:
firstly, checking whether an electrical switch, an electric wire, and the like of the equipment are good or not before use, checking whether the air tightness of the equipment is good or not, and checking whether all switches of the console are placed at 'off' positions or not.
And step two, if the electric switch and the electric wire of the pipe fitting assembling equipment are well grounded, the air tightness of the equipment is good, and the switches of the console are all arranged at the 'off' positions, the heating switch of the equipment is turned on, and all reaction chambers in the equipment are preheated and insulated.
And step three, after preheating is completed, adding tetrahydrofuran formic acid and R-type phenethylamine into the reaction chamber I, and performing resolution reaction on the tetrahydrofuran formic acid and the R-type phenethylamine to obtain tetrahydrofuran formic acid phenethylamine salt and resolution mother liquor.
And step four, filtering the obtained tetrahydrofuran benzoic acid phenethylamine salt and the split mother liquor, enabling the filtered tetrahydrofuran formic acid phenethylamine salt to enter a reaction chamber II, adding equivalent sulfuric acid into the reaction chamber II to dissociate the tetrahydrofuran formic acid phenethylamine salt to obtain phenethylamine sulfate and S-tetrahydrofuran formic acid, enabling the split mother liquor after filtering to enter a side reaction chamber, and adding S-type phenethylamine into the side reaction chamber to split the mixture to obtain a high-purity byproduct R-tetrahydrofuran formic acid.
And step five, filtering the obtained phenethylamine sulfate and S-tetrahydrofuran formic acid, filtering the phenethylamine sulfate, allowing the filtered S-tetrahydrofuran formic acid to enter a third reaction chamber, and adding carbonyl diimidazole into the third reaction chamber to form an active intermediate with the S-tetrahydrofuran formic acid.
And step six, dropwise adding methyl magnesium chloride into the active intermediate in the reaction chamber III to carry out Grignard reaction, and after the reaction is finished, carrying out simple post-treatment to obtain the target product acetyl tetrahydrofuran.
The synthesis process of acetyl tetrahydrofuran researched and produced by the invention takes tetrahydrofuran formic acid as a starting material, obtains a target product through resolution, dissociation, activation and Grignard reaction, has high reaction yield, can obtain high-purity R-tetrahydrofuran formic acid after resolution of a resolution mother liquor, can be sold as a byproduct, and reduces the production cost.
Preferably, the reaction yield of S-tetrahydrofuranic acid in step four is 38%, which is very high compared to the prior art.
Preferably, the reaction yield of the R-tetrahydrofuranic acid in step four is 35%, which is very high compared to the prior art.
Preferably, the reaction yield of acetyltetrahydrofuran in step six is 85%, which is very high compared to the prior art.
Preferably, the acetyltetrahydrofuran obtained in the sixth step is colorless or yellowish liquid, has a content of 97% or more, a moisture content of 0.2% or less, and an EE value of 97% or more, and has a very high purity as compared with the acetyltetrahydrofuran obtained in the prior art.
The invention also provides a production device of the acetyl tetrahydrofuran, which comprises a box body, wherein a box body cavity is arranged in the box body, a first chamber, a second chamber and a third chamber are respectively fixed in the cavity of the box body from top to bottom, a first charging opening and a second charging opening are respectively fixed on the upper end surface of the first chamber, the first feeding port and the second feeding port penetrate through the top of the cavity of the box body and are arranged outside the box body, the first discharging port is arranged at the bottom of the first cavity, a discharge port assembly is arranged in the first discharge port, a first feeding port and a first liquid supply assembly are respectively arranged on the upper end surface of the second chamber, the first feeding port and the second discharging port are arranged on the same horizontal straight line, a second discharging port is arranged at the bottom of the second chamber, the upper end face of the cavity III is respectively provided with a liquid supply component II, a liquid supply component III and a material inlet II matched with the material outlet II, and the bottom of the cavity III is provided with a material outlet III.
The device comprises a box body, wherein a box body cavity is arranged in the box body, a first cavity, a second cavity and a third cavity are respectively fixed in the box body cavity from top to bottom, a first feeding port and a second feeding port are respectively fixed on the upper end surface of the first cavity, the first feeding port and the second feeding port penetrate through the top of the box body cavity and are arranged outside the box body, a first discharging port is arranged at the bottom of the first cavity, a first discharging port assembly is arranged in the first discharging port, a first feeding port and a first liquid supply assembly are respectively arranged on the upper end surface of the second cavity, the first feeding port and the second discharging port assembly are arranged on the same horizontal straight line, a second discharging port is arranged at the bottom of the second cavity, a second liquid supply assembly, a third feeding port matched with the second discharging port are respectively arranged on the upper end surface of the third cavity, and a third discharging port is arranged at the bottom of the third cavity. The first feeding port is used for adding R-type phenethylamine, the second feeding port is used for adding tetrahydrofuran formic acid, the R-type phenethylamine and the tetrahydrofuran formic acid are subjected to splitting reaction in the first chamber, the obtained tetrahydrofuran formic acid phenethylamine salt is sent to the first feeding port through the discharging port assembly and then enters the second chamber, sulfuric acid is filled in the first liquid supply assembly and used for dissociating the tetrahydrofuran formic acid phenethylamine salt to obtain S-tetrahydrofuran formic acid, equivalent sulfuric acid replaces aqueous reagents such as hydrochloric acid, the dissociation yield is high and is 38%, the obtained S-tetrahydrofuran formic acid enters the third chamber through the second discharging port and the second feeding port, carbonyl diimidazole is filled in the second liquid supply assembly and used for activating the S-tetrahydrofuran formic acid, and methyl magnesium chloride is filled in the third liquid supply assembly and reacts with an active intermediate formed by the S-tetrahydrofuran formic acid and the carbonyl diimidazole, after the reaction is finished, the target product acetyl tetrahydrofuran can be obtained through simple post-treatment, the yield is 85%, the design well achieves the purpose of high reaction yield, in addition, the obtained mother liquor is split, S-type phenethylamine is used for splitting, high-purity R-tetrahydrofuran formic acid can be obtained, the yield is 35%, the R-tetrahydrofuran formic acid has wide application, and can be sold as a byproduct if being used for synthesizing faropenem, so that the production cost is reduced.
Preferably, the first chamber, the second chamber and the third chamber are sleeved with electric heating strips, the first chamber, the second chamber and the third chamber are fixed with rotary air cylinders at the central positions of the upper end faces, stirring rods are fixed on the rotary air cylinders, the three stirring rods penetrate through the three chambers respectively and are arranged in the three chambers, power plugs are arranged on the outer side faces of the box body, the electric heating strips and the rotary air cylinders are electrically connected with the power plugs, the added electric heating strips are used for heating the first chamber, the second chamber and the third chamber, the reaction rate can be improved, the added stirring rods are used for stirring mixed liquid in the first chamber, the second chamber and the third chamber, and the reaction rate can be further improved through heating.
Preferably, a sealing cover plate is clamped at the top of the box body, the top of the first feeding port and the top of the second feeding port penetrate through the sealing cover plate and are arranged outside the box body, the top of the first feeding port and the top of the second feeding port are respectively in threaded connection with a first cover body and a second cover body, the bottom of the first feeding port is arc-shaped, the outlet of the first feeding port is attached to the inner side wall of the first cavity, the discharge port assembly comprises a first valve body, the first valve body is fixed in the first discharge port, a first pipeline is installed on the first valve body, a second pipeline matched with the first pipeline is installed on the side wall of the cavity of the box body, one end of the second pipeline is arranged under the first pipeline, the other end of the first pipeline is arranged outside the box body, a third pipeline is arranged between the first pipeline and the second pipeline, the first pipeline and the second pipeline are both in sliding connection with the third pipeline, the slide block is arranged in the chute and is in sliding connection with the chute, a rotating motor is fixed on the slide block, the rotating motor is positioned on the side face of the pipeline III and is fixedly connected with the pipeline III, the rotating motor and the air cylinder are electrically connected with a power plug, a cover body I and a cover body II are additionally arranged for sealing a feeding port I and a feeding port II respectively, the air tightness of the interior of the box body is kept, a valve body I is a timing valve and is opened when the reaction in the cavity I is finished, a filter screen I in the pipeline III is used for filtering the obtained tetrahydrofuran benzoic acid phenethylamine salt, the tetrahydrofuran benzoic acid phenethylamine salt on the filter screen I is poured into the cavity II through the feeding port I through the matching of the air cylinder and the rotating motor, in addition, mother liquor obtained through the reaction in the cavity I is discharged out of the box body through the pipeline II, the mother liquor can be split by S-type phenethylamine, the R-tetrahydrofuran formic acid has wide application, can be used for synthesizing faropenem and can be sold as a byproduct, so that the production cost is reduced.
Preferably, the first feeding port and the third pipeline are arranged on the same horizontal straight line, the cross section of the top of the first feeding port is in a circular truncated cone shape, the first liquid supply assembly comprises a second valve body, the second valve body is arranged on the upper end face of the second chamber, a first liquid storage bottle is arranged on the second valve body, a second discharge port is arranged right above the second feeding port, a connecting pipeline is arranged between the second discharge port and the second feeding port, the third valve body is arranged on the connecting pipeline, a second filter screen is fixed at the bottom of the connecting pipeline, the top of the first feeding port is designed into a circular truncated cone shape, the third tetrahydrofuran benzoic acid phenethylamine salt is poured into the connecting pipeline conveniently, the second valve body is a timing valve, the second valve body is opened after the tetrahydrofuran benzoic acid phenethylamine salt is completely poured into the second chamber, sulfuric acid in the first liquid storage bottle flows into the second chamber, the tetrahydrofuran benzoic acid phenethylamine salt is dissociated to obtain S-tetrahydrofuran formic acid, and opening the system at the end of the liberation of the phenethylamine tetrahydrofuran formate, wherein the filter screen is used for filtering phenethylamine sulfate, and the S-tetrahydrofuran formate flows into the chamber III through a connecting pipeline.
Preferably, the liquid supply assembly II comprises a valve body IV, the liquid supply assembly III comprises a valve body V, the valve body IV and the valve body V are respectively arranged on the upper end surface of the chamber III, a liquid storage bottle II and a liquid storage bottle III are respectively fixed on the valve body IV and the valve body V, a valve body VI is fixed in the discharge port III, a liquid outlet channel matched with the valve body VI is arranged at the bottom of the box body, one end of the liquid outlet channel is fixed on the valve body VI, the other end of the liquid outlet channel is arranged outside the box body and is provided with a liquid outlet switch, the valve body IV and the valve body V are timing valves, the valve body IV is opened after S-tetrahydrofuran formic acid flows into the chamber III, carbonyl diimidazole in the liquid storage bottle II flows into the chamber III to form an active intermediate with the S-tetrahydrofuran formic acid, then the valve body V is opened, methyl magnesium chloride in the liquid storage bottle III, and opening the valve body six after the reaction is finished, enabling the solution to flow out of the box body through the liquid outlet channel and the liquid outlet switch, and performing simple post-treatment on the solution flowing out of the box body to obtain the target product acetyl tetrahydrofuran with the yield of 85%.
The invention has the beneficial effects that: tetrahydrofuran formic acid is used as an initial material, and a target object is obtained through resolution, dissociation, activation and Grignard reaction, wherein the total yield is 32%, and the reaction yield is high; after the split mother liquor is split, high-purity R-tetrahydrofuran formic acid can be obtained, the yield is 35%, the high-purity R-tetrahydrofuran formic acid can be sold as a byproduct, and the production cost is reduced; s-tetrahydrofuran formic acid is used as a starting material for synthesizing the acetyl tetrahydrofuran, the S-tetrahydrofuran formic acid and carbonyl diimidazole form an active intermediate, methyl magnesium chloride is dropwise added, the reaction is finished, and the target acetyl tetrahydrofuran can be obtained through simple post-treatment, wherein the yield is 85%; the electric heating tape and the stirring rod are additionally arranged and used for heating and stirring the first chamber, the second chamber and the third chamber, so that the reaction speed can be increased, and the reaction efficiency can be improved.
Drawings
FIG. 1 is a schematic structural view of the present invention;
FIG. 2 is a schematic structural view of the first chamber of FIG. 1;
FIG. 3 is a schematic structural view of the spout assembly of FIG. 1;
FIG. 4 is a schematic structural view of a second chamber of FIG. 1;
FIG. 5 is a schematic view of the structure of the connecting duct of FIG. 1;
fig. 6 is a schematic structural view of the chamber iii of fig. 1.
In the figure: 1. a cavity of the box body, 2, a first charging opening, 3, a sealing cover plate, 4, a second charging opening, 5, the box body, 6, a first chamber, 7, a first discharging opening, 8, a discharging opening component, 9, a first liquid supply component, 10, a second chamber, 11, a second discharging opening, 12, a second feeding opening, 13, a third chamber, 14, a liquid outlet switch, 15, a liquid outlet channel, 16, a third discharging opening, 17, a second liquid supply component, 18, a third liquid supply component, 19, a first feeding opening, 20, a power plug, 21, a stirring rod, 22, an electric heating belt, 23, a rotary cylinder, 24, a first cover body, 25, a second cover body, 26, a first valve body, 27, a first pipeline, 28, a third pipeline, 29, a first filter screen, 30, a second pipeline, 31, a sliding block, 32, a sliding chute, 33, a rotary motor, 34, a first liquid storage bottle, 35, a second valve body, 36, a connecting pipeline, 37, a third valve body, 40. and a third liquid storage bottle 41, a second liquid storage bottle 42, a fourth valve body 43 and a sixth valve body.
Detailed Description
The invention is further described with reference to the following figures and detailed description.
In the example of fig. 1, a process for the production of acetyltetrahydrofuran includes the following steps:
firstly, checking whether an electrical switch, an electric wire, and the like of the equipment are good or not before use, checking whether the air tightness of the equipment is good or not, and checking whether all switches of the console are placed at 'off' positions or not.
And step two, if the electric switch and the electric wire of the pipe fitting assembling equipment are well grounded, the air tightness of the equipment is good, and the switches of the console are all arranged at the 'off' positions, the heating switch of the equipment is turned on, and all reaction chambers in the equipment are preheated and insulated.
And step three, after preheating is completed, adding tetrahydrofuran formic acid and R-type phenethylamine into the reaction chamber I, and performing resolution reaction on the tetrahydrofuran formic acid and the R-type phenethylamine to obtain tetrahydrofuran formic acid phenethylamine salt and resolution mother liquor.
And step four, filtering the obtained tetrahydrofuran benzoic acid phenethylamine salt and the split mother liquor, enabling the filtered tetrahydrofuran formic acid phenethylamine salt to enter a reaction chamber II, adding equivalent sulfuric acid into the reaction chamber II to dissociate the tetrahydrofuran formic acid phenethylamine salt to obtain phenethylamine sulfate and S-tetrahydrofuran formic acid, enabling the split mother liquor after filtering to enter a side reaction chamber, and adding S-type phenethylamine into the side reaction chamber to split the mixture to obtain a high-purity byproduct R-tetrahydrofuran formic acid.
And step five, filtering the obtained phenethylamine sulfate and S-tetrahydrofuran formic acid, filtering the phenethylamine sulfate, allowing the filtered S-tetrahydrofuran formic acid to enter a third reaction chamber, and adding carbonyl diimidazole into the third reaction chamber to form an active intermediate with the S-tetrahydrofuran formic acid.
And step six, dropwise adding methyl magnesium chloride into the active intermediate in the reaction chamber III to carry out Grignard reaction, and after the reaction is finished, carrying out simple post-treatment to obtain the target product acetyl tetrahydrofuran.
The reaction yield of S-tetrahydrofuranic acid in step four was 38%.
The reaction yield of R-tetrahydrofuranic acid in step four was 35%.
The reaction yield of acetyltetrahydrofuran in the sixth step was 85%.
The acetyl tetrahydrofuran in the sixth step is colorless or light yellow liquid, the content of the acetyl tetrahydrofuran is more than or equal to 97 percent, the moisture of the acetyl tetrahydrofuran is less than or equal to 0.2 percent, and the EE value of the acetyl tetrahydrofuran is more than or equal to 97 percent.
As shown in figure 1, the invention also provides a device for producing acetyltetrahydrofuran, which comprises a box body 5, wherein a box body cavity 1 is arranged in the box body 5, and a first chamber 6, a second chamber 10 and a third chamber 13 are respectively fixed in the box body cavity 1 from top to bottom.
As shown in fig. 1 and 2, a first feed inlet 2 and a second feed inlet 4 are respectively fixed on the upper end surface of a first chamber 6, the first feed inlet 2 and the second feed inlet 4 both penetrate through the top of a cavity 1 of a box body and are arranged outside the box body 5, a first discharge outlet 7 is arranged at the bottom of the first chamber 6, a first discharge outlet assembly 8 is installed in the first discharge outlet 7, a first feed inlet 19 and a first liquid supply assembly 9 are respectively installed on the upper end surface of a second chamber 10, the first feed inlet 19 and the second discharge outlet assembly 8 are arranged on the same horizontal straight line, a second discharge outlet 11 is arranged at the bottom of the second chamber 10, a second liquid supply assembly 17, a third liquid supply assembly 18 and a second feed inlet 12 matched with the second discharge outlet 11 are respectively installed on the upper end surface of a third chamber 13.
As shown in fig. 1, the outer side surfaces of the first chamber 6, the second chamber 10 and the third chamber 13 are all sleeved with an electric heating belt 22, the central positions of the upper end surfaces of the first chamber 6, the second chamber 10 and the third chamber 13 are all fixed with a rotary cylinder 23, a stirring rod 21 is fixed on the rotary cylinder 23, the three stirring rods 21 respectively penetrate through the three chambers and are arranged in the three chambers, a power plug 20 is arranged on the outer side surface of the box body 5, and the electric heating belt 22 and the rotary cylinder 23 are both electrically connected with the power plug 20.
As shown in fig. 1, a sealing cover plate 3 is clamped at the top of the box body 5, the top of the first feeding port 2 and the top of the second feeding port 4 both penetrate through the sealing cover plate 3 and are arranged outside the box body 5, as shown in fig. 2, the top of the first feeding port 2 and the top of the second feeding port 4 are respectively in threaded connection with a first cover body 24 and a second cover body 25, the bottom of the first feeding port 2 is arc-shaped, and an outlet of the first feeding port 2 is attached to the inner side wall of the first cavity 6.
As shown in fig. 3, the discharge port assembly 8 includes a first valve body 26, the first valve body 26 is fixed in the first discharge port 7, a first pipeline 27 is installed on the first valve body 26, a second pipeline 30 matched with the first pipeline 27 is installed on the side wall of the box cavity 1, one end of the second pipeline 30 is arranged right below the first pipeline 27, the other end of the first pipeline 27 is arranged outside the box 5, a third pipeline 28 is arranged between the first pipeline 27 and the second pipeline 30, the first pipeline 27 and the second pipeline 30 are both connected with the third pipeline 28 in a sliding manner, and a first filter screen 29 is fixed at the bottom of the third pipeline 28.
As shown in fig. 1 and 3, a chute 32 is formed in the inner side wall of the box cavity 1, an air cylinder is fixed at the end of the chute 32, a sliding block 31 is fixed on the air cylinder, the sliding block 31 is installed in the chute 32 and is in sliding connection with the chute 32, a rotating motor 33 is fixed on the sliding block 31, the rotating motor 33 is located on the side surface of the pipeline three 28 and is fixedly connected with the pipeline three 28, and the rotating motor 33 and the air cylinder are both electrically connected with the power plug 20.
As shown in fig. 1 and 3, the first feeding port 19 and the third pipeline 28 are arranged on the same horizontal straight line, as shown in fig. 4, the cross section of the top of the first feeding port 19 is in a round table shape, the first liquid supply assembly 9 comprises a second valve body 35, the second valve body 35 is arranged on the upper end face of the second chamber 10, the first liquid storage bottle 34 is arranged on the second valve body 35, as shown in fig. 1 and 5, the second discharging port 11 is positioned right above the second feeding port 12, a connecting pipeline 36 is arranged between the second discharging port 11 and the second feeding port 12, the third valve body 37 is arranged on the connecting pipeline 36, and a second filter screen 38 is fixed at the bottom of the connecting pipeline 36.
As shown in fig. 1 and 6, the second liquid supply assembly 17 includes a fourth valve body 42, the third liquid supply assembly 18 includes a fifth valve body 39, the fourth valve body 42 and the fifth valve body 39 are respectively mounted on the upper end surface of the third chamber 13, a second liquid storage bottle 41 and a third liquid storage bottle 40 are respectively fixed on the fourth valve body 42 and the fifth valve body 39, a sixth valve body 43 is fixed in the third discharge port 16, a liquid outlet channel 15 matched with the sixth valve body 43 is arranged at the bottom of the box body 5, one end of the liquid outlet channel 15 is fixed on the sixth valve body 43, and the other end of the liquid outlet channel 15 is arranged outside the box body 5 and is provided with a liquid outlet.
During production, R-type phenylethylamine is added into the cavity I6 through the feeding port I2, tetrahydrofuran formic acid is added into the cavity II 10 through the feeding port II 4, and after the addition, the cover body I24 and the cover body II 5 are respectively covered, so that the R-type phenylethylamine and the tetrahydrofuran formic acid are subjected to splitting reaction in the cavity I6.
After the reaction is finished, the valve body I26 is opened, the separated tetrahydrofuran benzoic acid phenethylamine salt is filtered by the filter screen I29 in the pipeline III 28 and then is left on the filter screen I29 in the pipeline III 28, and then the tetrahydrofuran formic acid phenethylamine salt on the filter screen I29 is poured into the chamber II 10 through the feeding port I19 by the matching of the air cylinder and the rotating motor 33. After the tetrahydrofuran benzoic acid phenethylamine salt is completely poured into the second chamber 10, the second valve body 35 is opened, the sulfuric acid in the first liquid storage bottle 34 flows into the second chamber 10, and the tetrahydrofuran formic acid phenethylamine salt is dissociated.
After the dissociation is finished, S-tetrahydrofuran formic acid and phenethylamine sulfate are obtained, then the valve body III 37 is opened, the filter screen II 38 is used for filtering the phenethylamine sulfate, and the S-tetrahydrofuran formic acid flows into the chamber III 13 through the connecting pipeline 36. After the S-tetrahydrofuran formic acid flows into the chamber III 13, the valve body IV 42 is opened, and the carbonyldiimidazole in the liquid storage bottle II 41 flows into the chamber III 13 to form an active intermediate with the S-tetrahydrofuran formic acid. Then the valve body five 39 is opened, and the methyl magnesium chloride in the liquid storage bottle three 40 flows into the chamber three 13 to carry out Grignard reaction with the active intermediate.
And after the reaction is finished, opening the valve body six 43, allowing the solution to flow out of the box body through the liquid outlet channel 15 and the liquid outlet switch 14, and finally performing simple post-treatment on the solution flowing out of the box body 5 to obtain the target product acetyl tetrahydrofuran.
Claims (10)
1. A method for producing acetyltetrahydrofuran, comprising the steps of:
firstly, checking whether an electrical switch, an electric wire, and the like of the equipment are good or not before use, checking whether the air tightness of the equipment is good or not, and checking whether all switches of the console are placed at 'off' positions or not.
And step two, if the electric switch and the electric wire of the pipe fitting assembling equipment are well grounded, the air tightness of the equipment is good, and the switches of the console are all arranged at the 'off' positions, the heating switch of the equipment is turned on, and all reaction chambers in the equipment are preheated and insulated.
And step three, after preheating is completed, adding tetrahydrofuran formic acid and R-type phenethylamine into the reaction chamber I, and performing resolution reaction on the tetrahydrofuran formic acid and the R-type phenethylamine to obtain tetrahydrofuran formic acid phenethylamine salt and resolution mother liquor.
And step four, filtering the obtained tetrahydrofuran benzoic acid phenethylamine salt and the split mother liquor, enabling the filtered tetrahydrofuran formic acid phenethylamine salt to enter a reaction chamber II, adding equivalent sulfuric acid into the reaction chamber II to dissociate the tetrahydrofuran formic acid phenethylamine salt to obtain phenethylamine sulfate and S-tetrahydrofuran formic acid, enabling the split mother liquor after filtering to enter a side reaction chamber, and adding S-type phenethylamine into the side reaction chamber to split the mixture to obtain a high-purity byproduct R-tetrahydrofuran formic acid.
And step five, filtering the obtained phenethylamine sulfate and S-tetrahydrofuran formic acid, filtering the phenethylamine sulfate, allowing the filtered S-tetrahydrofuran formic acid to enter a third reaction chamber, and adding carbonyl diimidazole into the third reaction chamber to form an active intermediate with the S-tetrahydrofuran formic acid.
And step six, dropwise adding methyl magnesium chloride into the active intermediate in the reaction chamber III to carry out Grignard reaction, and after the reaction is finished, carrying out simple post-treatment to obtain the target product acetyl tetrahydrofuran.
2. The process according to claim 1, wherein the yield of S-tetrahydrofuranic acid in step IV is 38%.
3. The process for producing acetyltetrahydrofuran according to claim 1, wherein the reaction yield of R-tetrahydrofuranic acid in the fourth step is 35%.
4. The process for producing acetyltetrahydrofuran according to claim 1, wherein the reaction yield of acetyltetrahydrofuran in the sixth step is 85%.
5. The process according to claim 1, wherein the acetyltetrahydrofuran obtained in the sixth step is a colorless or pale yellow liquid having a water content of 97% or more, a water content of 0.2% or less, and an EE value of 97% or more.
6. The utility model provides a production device of acetyl tetrahydrofuran, characterized by, includes box (5), box (5) inside is equipped with box cavity (1), from the top down is fixed with chamber one (6), chamber two (10) and chamber three (13) respectively in box cavity (1), the up end of chamber one (6) is fixed with charge door one (2) and charge door two (4) respectively, charge door one (2) and charge door two (4) all run through the top of box cavity (1) and place outside box (5), the bottom of chamber one (6) is equipped with discharge gate one (7), install discharge gate subassembly (8) in discharge gate one (7), the up end of chamber two (10) is installed respectively and is gone into charge door one (19) and supply liquid subassembly one (9), charge door one (19) and discharge gate subassembly (8) are arranged in on same horizontal straight line, the bottom of the second chamber (10) is provided with a second discharge hole (11), the upper end face of the third chamber (13) is respectively provided with a second liquid supply assembly (17), a third liquid supply assembly (18) and a second feed inlet (12) matched with the second discharge hole (11), and the bottom of the third chamber (13) is provided with a third discharge hole (16).
7. The production device of acetyl tetrahydrofuran according to claim 6, wherein the outer side surfaces of the first chamber (6), the second chamber (10) and the third chamber (13) are respectively sleeved with an electric heating belt (22), the center positions of the upper end surfaces of the first chamber (6), the second chamber (10) and the third chamber (13) are respectively fixed with a rotary cylinder (23), the rotary cylinder (23) is fixed with a stirring rod (21), the three stirring rods (21) respectively penetrate through the three chambers and are arranged in the three chambers, the outer side surface of the box body (5) is provided with a power plug (20), and the electric heating belts (22) and the rotary cylinder (23) are electrically connected with the power plug (20).
8. The production device of acetyl tetrahydrofuran according to claim 7, wherein the top of the box (5) is connected with a sealing cover plate (3), the top of the first feeding port (2) and the top of the second feeding port (4) both penetrate through the sealing cover plate (3) and are arranged outside the box (5), the top of the first feeding port (2) and the top of the second feeding port (4) are respectively connected with a first cover body (24) and a second cover body (25) in a threaded manner, the bottom of the first feeding port (2) is arc-shaped, the outlet of the first feeding port is attached to the inner side wall of the first chamber (6), the discharge port assembly (8) comprises a first valve body (26), the first valve body (26) is fixed in the first discharge port (7), the first valve body (26) is provided with a first pipeline (27), the side wall of the box cavity (1) is provided with a second pipeline (30) matched with the first pipeline (27), one end of the second pipeline (30) is arranged right below the first pipeline (27), the other end of the first pipeline (27) is arranged outside the box body (5), a third pipeline (28) is arranged between the first pipeline (27) and the second pipeline (30), the first pipeline (27) and the second pipeline (30) are both connected with the third pipeline (28) in a sliding way, a first filter screen (29) is fixed at the bottom of the third pipeline (28), a chute (32) is arranged on the inner side wall of the box body cavity (1), an air cylinder is fixed at the end part of the chute (32), a sliding block (31) is fixed on the air cylinder, the sliding block (31) is arranged in the sliding groove (32) and is connected with the sliding groove (32) in a sliding way, a rotating motor (33) is fixed on the sliding block (31), the rotating motor (33) is positioned on the side surface of the pipeline III (28) and is fixedly connected with the pipeline III (28), the rotating motor (33) and the air cylinder are electrically connected with a power plug (20).
9. The production device of acetyl tetrahydrofuran according to claim 8, wherein the first inlet (19) and the third pipe (28) are arranged on the same water straight line, the cross section of the top of the first inlet (19) is in a shape of a circular truncated cone, the first liquid supply assembly (9) comprises a second valve body (35), the second valve body (35) is arranged on the upper end face of the second chamber (10), the second valve body (35) is provided with a first liquid storage bottle (34), the second outlet (11) is arranged right above the second inlet (12), a connecting pipe (36) is arranged between the second outlet (11) and the second inlet (12), the third valve body (37) is arranged on the connecting pipe (36), and a second filter screen (38) is fixed at the bottom of the connecting pipe (36).
10. The production device of acetyl tetrahydrofuran according to claim 1, wherein the liquid supply assembly II (17) comprises a valve body IV (42), the liquid supply assembly III (18) comprises a valve body V (39), the valve body IV (42) and the valve body V (39) are respectively installed on the upper end face of the chamber III (13), the valve body IV (42) and the valve body V (39) are respectively fixed with a liquid storage bottle II (41) and a liquid storage bottle III (40), the discharge port III (16) is internally fixed with a valve body VI (43), the bottom of the box body (5) is provided with a liquid outlet channel (15) matched with the valve body VI (43), one end of the liquid outlet channel (15) is fixed on the valve body VI (43), and the other end of the liquid outlet channel (15) is arranged outside the box body (5) and is provided with the liquid outlet switch (14).
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040039197A1 (en) * | 2001-09-03 | 2004-02-26 | Heinz Weinberger | Cyclic indole and heteroindole derivatives and methods for making and using as pharmaceuticals |
| CN1551885A (en) * | 2001-09-03 | 2004-12-01 | Cyclic indole and heteroindole derivatives, the production and use thereof as medicaments | |
| CN101429180A (en) * | 2007-11-09 | 2009-05-13 | 雅本化学（苏州）有限公司 | Process for producing S-tetrahydrochysene furoic acid |
| CN105566257A (en) * | 2016-01-04 | 2016-05-11 | 成都丽凯手性技术有限公司 | Industrial preparation method of acetyl tetrahydrofuran with high optical purity |
| CN105669606A (en) * | 2016-01-04 | 2016-06-15 | 成都丽凯手性技术有限公司 | Industrial preparation method of high-optical purity 1-[tetrahydro-2-furyl]ethanone |
-
2020
- 2020-04-01 CN CN202010250879.0A patent/CN111362891A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040039197A1 (en) * | 2001-09-03 | 2004-02-26 | Heinz Weinberger | Cyclic indole and heteroindole derivatives and methods for making and using as pharmaceuticals |
| CN1551885A (en) * | 2001-09-03 | 2004-12-01 | Cyclic indole and heteroindole derivatives, the production and use thereof as medicaments | |
| CN101429180A (en) * | 2007-11-09 | 2009-05-13 | 雅本化学（苏州）有限公司 | Process for producing S-tetrahydrochysene furoic acid |
| CN105566257A (en) * | 2016-01-04 | 2016-05-11 | 成都丽凯手性技术有限公司 | Industrial preparation method of acetyl tetrahydrofuran with high optical purity |
| CN105669606A (en) * | 2016-01-04 | 2016-06-15 | 成都丽凯手性技术有限公司 | Industrial preparation method of high-optical purity 1-[tetrahydro-2-furyl]ethanone |
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