CN108129267B - Low-temperature full-continuous reaction system and application - Google Patents
Low-temperature full-continuous reaction system and application Download PDFInfo
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- CN108129267B CN108129267B CN201810026913.9A CN201810026913A CN108129267B CN 108129267 B CN108129267 B CN 108129267B CN 201810026913 A CN201810026913 A CN 201810026913A CN 108129267 B CN108129267 B CN 108129267B
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- 238000006243 chemical reaction Methods 0.000 title claims abstract description 153
- 238000010791 quenching Methods 0.000 claims abstract description 130
- 230000000171 quenching effect Effects 0.000 claims abstract description 103
- 239000000047 product Substances 0.000 claims abstract description 83
- 238000000926 separation method Methods 0.000 claims abstract description 51
- 239000012043 crude product Substances 0.000 claims abstract description 50
- 239000007788 liquid Substances 0.000 claims abstract description 38
- 239000012074 organic phase Substances 0.000 claims description 74
- 239000010409 thin film Substances 0.000 claims description 37
- 239000002274 desiccant Substances 0.000 claims description 35
- 239000010408 film Substances 0.000 claims description 25
- 239000003153 chemical reaction reagent Substances 0.000 claims description 24
- 239000008346 aqueous phase Substances 0.000 claims description 23
- 238000001035 drying Methods 0.000 claims description 22
- FMDMKDPUFQNVSH-UHFFFAOYSA-N ethyl 3,3,3-trifluoropropanoate Chemical compound CCOC(=O)CC(F)(F)F FMDMKDPUFQNVSH-UHFFFAOYSA-N 0.000 claims description 19
- 238000000605 extraction Methods 0.000 claims description 18
- 229910052751 metal Inorganic materials 0.000 claims description 18
- 239000002184 metal Substances 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 16
- 238000001704 evaporation Methods 0.000 claims description 15
- 230000008020 evaporation Effects 0.000 claims description 15
- 239000002994 raw material Substances 0.000 claims description 15
- 239000002904 solvent Substances 0.000 claims description 15
- 230000008569 process Effects 0.000 claims description 14
- 238000003860 storage Methods 0.000 claims description 13
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 claims description 11
- 230000009467 reduction Effects 0.000 claims description 7
- HDBGBTNNPRCVND-UHFFFAOYSA-N 3,3,3-trifluoropropan-1-ol Chemical compound OCCC(F)(F)F HDBGBTNNPRCVND-UHFFFAOYSA-N 0.000 claims description 4
- 239000006227 byproduct Substances 0.000 abstract description 19
- 238000005516 engineering process Methods 0.000 abstract description 10
- 239000012535 impurity Substances 0.000 abstract description 9
- 239000000463 material Substances 0.000 abstract description 7
- 238000004519 manufacturing process Methods 0.000 abstract 1
- 239000003795 chemical substances by application Substances 0.000 description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 238000000746 purification Methods 0.000 description 10
- 238000010924 continuous production Methods 0.000 description 6
- 230000000694 effects Effects 0.000 description 5
- 239000002699 waste material Substances 0.000 description 5
- 238000009825 accumulation Methods 0.000 description 4
- 238000010923 batch production Methods 0.000 description 4
- 238000005265 energy consumption Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical group CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- FWFGVMYFCODZRD-UHFFFAOYSA-N oxidanium;hydrogen sulfate Chemical compound O.OS(O)(=O)=O FWFGVMYFCODZRD-UHFFFAOYSA-N 0.000 description 3
- 238000001179 sorption measurement Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
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- 239000012071 phase Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical group [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical group [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000005111 flow chemistry technique Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- -1 preferably Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
- C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
- C07C29/147—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of carboxylic acids or derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/74—Separation; Purification; Use of additives, e.g. for stabilisation
- C07C29/76—Separation; Purification; Use of additives, e.g. for stabilisation by physical treatment
- C07C29/78—Separation; Purification; Use of additives, e.g. for stabilisation by physical treatment by condensation or crystallisation
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Crystallography & Structural Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a low-temperature full-continuous reaction system and application thereof. The low-temperature full-continuous reaction system comprises: a low temperature continuous reaction unit having a crude product system outlet; a continuous quenching unit having a crude product system inlet and a quenched product outlet, the crude product system outlet being connected to the crude product system inlet; the continuous liquid separation unit is provided with a quenching product inlet and a crude product outlet, and the quenching product outlet is connected with the quenching product inlet; and a continuous film concentration unit having a crude product inlet and a product outlet, the crude product outlet being connected to the crude product inlet. The continuous reaction technology is utilized to realize low-temperature reaction, the reaction temperature is milder, the production of byproducts and impurities is better controlled, and the purity and the yield of the product are improved; the material after the low-temperature reaction is subjected to continuous post-treatment by a continuous quenching unit, a continuous liquid separation unit and a continuous film concentration unit, so that the target product can be separated in time, and the separation efficiency and the yield of the target product are improved.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a low-temperature full-continuous reaction system and application.
Background
Compared with the traditional chemical device, the continuous flow chemistry is a revolutionary technology for subverting the traditional chemical, opens a brand-new efficient refined era for the pharmaceutical chemical industry, and provides an effective technical means for transformation upgrading, improving innovation capability and realizing zero emission, green and sustainable development of the pharmaceutical industry.
Continuous flow reactors provide an efficient tool for this purpose. Compared with the traditional kettle-type reactor, the continuous flow reactor has the advantages of large specific surface area, high transfer rate, short contact time, less byproducts, higher conversion rate, good operability, high safety, rapid and direct amplification and the like, and each condition (reactants, products, byproducts, catalysts, solvents, media) of the continuous flow reaction is micronized, and the reaction conditions such as temperature, pressure and the like can be more precisely regulated and controlled. And the continuous flow reactor has the advantages of low heat buffering demand, improved yield, reduced reagent, extremely high automation degree and great manpower resource saving.
In the medical field, continuous flow reaction technology is used to replace the traditional batch process kettle reaction technology, and is receiving high attention and rapidly developing from various medical companies. In the field of pharmaceutical synthesis, the post-treatment technology still maintains its original state, and is a batch process, i.e. a traditional reaction kettle is required to perform post-treatment operations such as extraction, washing, concentration, drying, crystallization, etc. on the reacted mixture. Such conventional, inefficient batch post-treatment processes are creating bottlenecks to efficient continuous reaction techniques and are in urgent need for improvement.
Disclosure of Invention
The invention mainly aims to provide a low-temperature full-continuous reaction system and application thereof, so as to solve the problem of low treatment efficiency after low-temperature reaction in the prior art.
In order to achieve the above object, according to one aspect of the present invention, there is provided a low-temperature full-continuous reaction system comprising: a low temperature continuous reaction unit having a crude product system outlet; a continuous quenching unit having a crude product system inlet and a quenched product outlet, the crude product system outlet being connected to the crude product system inlet; the continuous liquid separation unit is provided with a quenching product inlet and a crude product outlet, and the quenching product outlet is connected with the quenching product inlet; and a continuous film concentration unit having a crude product inlet and a product outlet, the crude product outlet being connected to the crude product inlet.
Further, the continuous quenching unit includes: the primary quenching reaction device is provided with a first quenching agent inlet, a primary quenching product outlet and a crude product system inlet; the secondary quenching reaction device is provided with a second quenching agent inlet, a primary quenching product inlet and a quenching product outlet, and the primary quenching product outlet is connected with the primary quenching product inlet; the first quencher supply device is connected with the first quencher inlet through a third automatic feeding pump; and the second quenching agent supply device is connected with the second quenching agent inlet through a fourth automatic feeding pump.
Further, the first-stage quenching reaction device is a second coil reactor, and preferably the second coil reactor is provided with a second temperature controller; preferably, the secondary quenching reaction device is a continuous reaction kettle, and further preferably, the continuous reaction kettle is provided with a third temperature controller.
Further, the continuous liquid separation unit includes: the continuous liquid separation column is provided with a first organic phase outlet, a water phase outlet and a quenching product inlet, and the quenching product outlet is connected with the quenching product inlet through a fifth automatic feeding pump; the continuous extraction separation column is provided with an extractant inlet, an aqueous phase inlet and a second organic phase outlet, and the aqueous phase outlet is connected with the aqueous phase inlet through a sixth automatic feed pump; the organic phase buffer storage tank is provided with a first organic phase inlet and a crude product outlet, the first organic phase outlet and the second organic phase outlet are connected with the first organic phase inlet, and the extractant supply device is connected with the extractant inlet; preferably the continuous separation column has a fourth temperature controller, preferably the continuous extraction separation column has a fifth temperature controller.
Further, the continuous film concentration unit includes: a continuous drying column having a desiccant inlet, a third organic phase outlet, and a crude product inlet, the crude product outlet being connected to the crude product inlet by a seventh automatic feed pump; the continuous film evaporation device is provided with a second organic phase inlet and a product outlet, and the third organic phase outlet is connected with the second organic phase inlet through an eighth automatic feeding pump.
Further, the continuous film concentration unit further comprises a continuous desiccant supply device connected with the desiccant inlet.
Further, the continuous drying agent supply device is a screw feeder; preferably, the continuous drying column has a sixth temperature controller.
Further, the continuous thin film evaporation apparatus described above includes: a first continuous thin film evaporator having a second organic phase inlet and a fourth organic phase outlet; the second continuous thin film evaporator is provided with a third organic phase inlet, an azeotropic solvent inlet and a product outlet, and the fourth organic phase outlet is connected with the third organic phase inlet through a ninth automatic feed pump; and the azeotropic solvent supply device is connected with the azeotropic solvent inlet through a tenth automatic feed pump.
Further, the first continuous thin film evaporator has a seventh temperature controller, and the second continuous thin film evaporator has an eighth temperature controller.
Further, the low-temperature continuous reaction unit includes: a first raw material supply device; a sensitive metal reagent supply device; the low-temperature continuous reaction device is provided with a first raw material inlet, a sensitive metal reagent inlet and a crude product system outlet, wherein the first raw material supply device is connected with the first raw material inlet through a first automatic feed pump, and the sensitive metal reagent supply device is connected with the sensitive metal reagent inlet through a second automatic feed pump; preferably, the low temperature continuous reaction apparatus is a first coil reactor, and more preferably the first coil reactor has a first temperature controller.
According to another aspect of the present invention, there is provided the use of any of the above described low temperature fully continuous reaction systems in low temperature fully continuous reactions.
Further, the above-mentioned application includes a reaction of reducing ethyl trifluoropropionate by diisobutylaluminum hydride to prepare trifluoropropanol and a post-treatment process, and preferably the reduction temperature of reducing ethyl trifluoropropionate by diisobutylaluminum hydride is-30-0 ℃.
By applying the technical scheme of the invention, the low-temperature full-continuous reaction system comprises a low-temperature continuous reaction unit, namely, the low-temperature reaction is realized by utilizing a continuous reaction technology, so that the heat energy of the low-temperature reaction is effectively improved, the reaction temperature is further milder, the generation of byproducts and impurities is better controlled, and the purity and the yield of the product are improved; the material after the low-temperature reaction is subjected to continuous post-treatment by the continuous quenching unit, the continuous liquid separating unit and the continuous film concentrating unit, so that the target product obtained after the low-temperature reaction can be separated in time, the increase of byproducts caused by product accumulation is avoided, the separation efficiency and the yield of the target product are further improved, and the energy and the reagent consumed by the product purification are reduced due to the reduction of byproducts and impurities, namely, the energy consumption, the waste emission and the treatment cost of the product purification are reduced. Meanwhile, the application of the low-temperature full-continuous reaction system ensures that the equipment is simple and convenient to operate, the safety is improved, the working strength of operators is reduced, and the labor cost is also reduced.
Drawings
The accompanying drawings, which are included to provide a further understanding of the application and are incorporated in and constitute a part of this specification, illustrate embodiments of the application and together with the description serve to explain the application. In the drawings:
FIG. 1 shows a schematic structural diagram of a low temperature fully-continuous reaction system provided according to one embodiment of the present invention; and
Fig. 2 shows a schematic structural diagram of a low-temperature full-continuous reaction system according to another embodiment of the present invention.
Wherein the above figures include the following reference numerals:
10. a low-temperature continuous reaction unit; 11. a first raw material supply device; 12. a sensitive metal reagent supply device; 13. a low-temperature continuous reaction device; 14. a first automatic feed pump; 15. a second automatic feed pump;
20. A continuous quenching unit; 21. a primary quenching reaction device; 22. a secondary quenching reaction device; 23. a first quencher supply; 24. a second quencher supply; 25. a third automatic feed pump; 26. a fourth automatic feed pump;
30. A continuous liquid separation unit; 31. a continuous liquid separation column; 32. a continuous extraction separation column; 33. an organic phase buffer storage tank; 34. an extractant supply device; 35. a fifth automatic feed pump; 36. a sixth automatic feed pump;
40. A continuous film concentration unit; 41. a continuous drying column; 42. a continuous thin film evaporation device; 43. a continuous supply of desiccant; 421. a first continuous thin film evaporator; 422. a second continuous thin film evaporator; 423. azeotropic solvent supply means; 44. a seventh automatic feed pump; 45. an eighth automatic feed pump; 46. a ninth automatic feed pump; 47. tenth automatic feed pump.
Detailed Description
It should be noted that, without conflict, the embodiments of the present application and features of the embodiments may be combined with each other. The application will be described in detail below with reference to the drawings in connection with embodiments.
As analyzed in the background of the application, the post-treatment of the pharmaceutical synthesis technology in the prior art adopts a batch process, which results in lower post-treatment efficiency.
In an exemplary embodiment of the present application, there is provided a low temperature full-continuous reaction system, as shown in fig. 1, which includes a low temperature continuous reaction unit 10, a continuous quenching unit 20, a continuous liquid separation unit 30, and a continuous thin film concentration unit 40, the low temperature continuous reaction unit 10 having a crude product system outlet; the continuous quench unit 20 has a crude product system inlet and a quench product outlet, the crude product system outlet being connected to the crude product system inlet; the continuous liquid separation unit 30 has a quenched product inlet and a crude product outlet, the quenched product outlet being connected to the quenched product inlet; the continuous film concentration unit 40 has a crude product inlet and a product outlet, the crude product outlet being connected to the crude product inlet.
The low-temperature full-continuous reaction system comprises a low-temperature continuous reaction unit 10, namely, the low-temperature reaction is realized by utilizing a continuous reaction technology, so that the heat energy of the low-temperature reaction is effectively improved, the reaction temperature is further milder, the generation of byproducts and impurities is better controlled, and the purity and the yield of the product are improved; the material after the low-temperature reaction is subjected to continuous post-treatment by the continuous quenching unit 20, the continuous liquid separating unit 30 and the continuous film concentrating unit 40, so that the target product obtained after the low-temperature reaction can be separated in time, the increase of byproducts caused by product accumulation is avoided, the separation efficiency and the yield of the target product are further improved, and the energy and the reagent consumed by the product purification are reduced due to the reduction of byproducts and impurities, namely, the energy consumption, the waste emission and the treatment cost of the product purification are reduced. Meanwhile, the application of the low-temperature full-continuous reaction system ensures that the equipment is simple and convenient to operate, the safety is improved, the working strength of operators is reduced, and the labor cost is also reduced.
Preferably, as shown in fig. 2, the continuous quenching unit 20 includes a primary quenching reaction device 21, a secondary quenching reaction device 22, a first quenching agent supply device 23 and a second quenching agent supply device 24, wherein the primary quenching reaction device 21 has a first quenching agent inlet, a primary quenching product outlet and a crude product system inlet; the secondary quench reaction device 22 has a second quench inlet, a primary quench product inlet, and a quench product outlet, the primary quench product outlet being connected to the primary quench product inlet; the first quencher supply means 23 is connected to the first quencher inlet via a third automatic feed pump 25; the second quencher supply 24 is connected to the second quencher inlet via a fourth automatic feed pump 26. The first quench inlet may be the same port as the crude system inlet.
The two-stage quenching is adopted to realize the step-by-step stable quenching of the low-temperature reaction, wherein the third automatic feeding pump 25 is utilized to automatically feed the first-stage quenching reaction device 21, the fourth automatic feeding pump 26 is utilized to automatically feed the second-stage quenching reaction device 22, the accurate feeding of the quenching agent is realized, and the quenching speed is adjusted according to the actual reaction.
The primary quenching reaction device 21 and the secondary quenching reaction device 22 may be continuous reaction devices commonly used in the prior art, and in one embodiment of the present application, the primary quenching reaction device 21 is a second coil reactor, preferably the second coil reactor has a second temperature controller; the second coil reactor is adopted as the primary quenching reaction device 21, the characteristics of the coil reactor are utilized to enable the quenching agent and unreacted complete materials to be in more sufficient contact, rapid quenching reaction is realized, and a second temperature controller is arranged in the second coil reactor, so that the quenching efficiency is further improved by implementing temperature adjustment. Further, the secondary quenching reaction device 22 is preferably a continuous reaction vessel, and further preferably the continuous reaction vessel is provided with a third temperature controller. Since the primary quenching reaction has completed most of the quenching of the low-temperature continuous reaction, the continuous quenching at low cost can be realized by adopting the continuous reaction kettle as the secondary quenching reaction device 22; further, the temperature of the continuous reaction kettle is controlled through the third temperature controller, so that the accurate control of the quenching reaction progress is realized, the quenching reaction efficiency is improved, and unnecessary waste of the quenching agent is reduced.
The continuous liquid separation unit 30 may adjust its specific structural composition according to a specific reaction, preferably as shown in fig. 2, the continuous liquid separation unit 30 includes a continuous liquid separation column 31, a continuous extraction separation column 32, an organic phase buffer storage tank 33, and an extractant supply device 34, the continuous liquid separation column 31 has a first organic phase outlet, an aqueous phase outlet, and a quenching product inlet, and the quenching product outlet and the quenching product inlet are connected through a fifth automatic feed pump 35; the continuous extraction separation column 32 has an extractant inlet, an aqueous phase inlet, and a second organic phase outlet, the aqueous phase outlet being connected to the aqueous phase inlet by a sixth automatic feed pump 36; the organic phase buffer tank 33 has a first organic phase inlet and a crude product outlet, the first organic phase outlet and the second organic phase outlet being connected to the first organic phase inlet, and the extractant supply 34 being connected to the extractant inlet. Separating the quenched product by means of a continuous separation column 31, thereby achieving a preliminary separation of the organic and aqueous phases without the need for any addition of reagents; the aqueous phase is then subjected to extraction separation of the organic phase therein using a continuous extraction separation column 32 to effect further recovery of the target product. In order to improve the separation efficiency, it is preferable that the continuous liquid separation column 31 has a fourth temperature controller, and it is preferable that the continuous extraction separation column 32 has a fifth temperature controller.
The continuous film concentration unit 40 is used for further separating and purifying the organic phase separated by the continuous liquid separation unit 30, preferably as shown in fig. 2, the continuous film concentration unit 40 includes a continuous drying column 41 and a continuous film evaporation device 42, the continuous drying column 41 has a desiccant inlet, a third organic phase outlet and a crude product inlet, and the crude product outlet and the crude product inlet are connected by a seventh automatic feed pump 44; the continuous thin film evaporation apparatus 42 has a second organic phase inlet and a product outlet, and the third organic phase outlet is connected to the second organic phase inlet by an eighth automatic feed pump 45. The residual aqueous phase in the organic phase is subjected to an absorption treatment by the above-mentioned continuous drying column 41, thereby improving the purity of the organic phase; the purified organic phase is then subjected to a continuous evaporation process by means of a continuous thin film evaporation device 42, and efficient separation of the product is achieved by means of the efficient, high purity separation characteristics of thin film evaporation.
In order to facilitate the adjustment of the amount of desiccant used according to the concentration of the aqueous phase in the organic phase, the continuous film concentration unit 40 preferably further comprises a continuous supply of desiccant 43, wherein the continuous supply of desiccant 43 is connected to the desiccant inlet. The desiccant is continuously supplied by the desiccant continuous supply device 43, and the amount of the desiccant is adjusted by adjusting the supply speed of the desiccant, thereby improving the utilization efficiency of the desiccant.
Preferably, the desiccant continuous supply device 43 supplies the desiccant, preferably, the desiccant is solid desiccant, and further preferably, the desiccant continuous supply device 43 is a screw feeder. Further, in order to enhance the adsorption effect of the desiccant on the aqueous phase in the organic phase, it is preferable that the continuous drying column 41 has a sixth temperature controller to adjust the adsorption temperature and enhance the adsorption effect of the desiccant.
In another embodiment of the present application, as shown in fig. 2, the continuous thin film evaporator 42 includes a first continuous thin film evaporator 421, a second continuous thin film evaporator 422, and an azeotropic solvent supply device 423, where the first continuous thin film evaporator 421 has a second organic phase inlet and a fourth organic phase outlet; the second continuous thin film evaporator 422 has a third organic phase inlet, an azeotropic solvent inlet and a product outlet, the fourth organic phase outlet being connected to the third organic phase inlet by a ninth automatic feed pump 46; the azeotropic solvent supply 423 is connected to the azeotropic solvent inlet via a tenth automatic feed pump 47. The dried organic phase is subjected to evaporation treatment by arranging a first continuous thin film evaporator 421 so as to purify the target product, and then the organic phase is subjected to further evaporation treatment by arranging a second continuous thin film evaporator 422 under the condition of participation of an entrainer, so that the purification of the target product is realized. The entrainer is provided by the entrainer supply to ensure stable and continuous operation of the second continuous thin film evaporator 422. The entrainer inlet and the third organic inlet may be the same inlet.
Preferably, the first continuous thin film evaporator 421 has a seventh temperature controller, and the second continuous thin film evaporator 422 has an eighth temperature controller. So as to control the temperature of the film evaporation and improve the purification efficiency of the target product.
The low-temperature full-continuous reaction system of the application is applied to various low-temperature reactions, is particularly suitable for the low-temperature reactions involving sensitive metal reagents, and preferably as shown in fig. 2, the low-temperature continuous reaction unit 10 comprises a first raw material supply device 11, a sensitive metal reagent supply device 12 and a low-temperature continuous reaction device 13, the low-temperature continuous reaction device 13 is provided with a first raw material inlet, a sensitive metal reagent inlet and a crude product system outlet, the first raw material supply device 11 is connected with the first raw material inlet through a first automatic feed pump 14, and the sensitive metal reagent supply device 12 is connected with the sensitive metal reagent inlet through a second automatic feed pump 15. The first automatic feeding pump 14 and the second automatic feeding pump 15 are utilized to control the feeding speed of reactants participating in the reaction, thereby adjusting the retention time of the low-temperature reaction, and simultaneously adjusting the speed of each follow-up moving feeding pump according to the feeding speed of the first automatic feeding pump 14 and the second automatic feeding pump 15.
Further, the low-temperature continuous reaction apparatus 13 is preferably a first coil reactor, and more preferably the first coil reactor has a first temperature controller. Of course, the low-temperature continuous reaction device 13 can also be a continuous reaction kettle, and the advantage of adopting the first coil reactor is that the contact of materials is better, and the reaction efficiency is higher.
In another exemplary embodiment of the present application, there is provided a use of any of the above described low temperature full-continuous reaction systems in a low temperature full-continuous reaction.
When the low-temperature full-continuous reaction system is applied to the low-temperature full-continuous reaction, the continuous reaction technology is utilized to realize the low-temperature reaction, so that the heat energy of the low-temperature reaction is effectively improved, the reaction temperature is further milder, the generation of byproducts and impurities is better controlled, and the purity and the yield of the product are improved; the material after the low-temperature reaction is subjected to continuous post-treatment by the continuous quenching unit 20, the continuous liquid separating unit 30 and the continuous film concentrating unit 40, so that the target product obtained after the low-temperature reaction can be separated in time, the increase of byproducts caused by product accumulation is avoided, the separation efficiency and the yield of the target product are further improved, and the energy and the reagent consumed by the product purification are reduced due to the reduction of byproducts and impurities, namely, the energy consumption, the waste emission and the treatment cost of the product purification are reduced. Meanwhile, the application of the low-temperature full-continuous reaction system ensures that the equipment is simple and convenient to operate, the safety is improved, the working strength of operators is reduced, and the labor cost is also reduced.
Preferably, the above-mentioned applications include the reaction of diisobutylaluminum hydride to prepare trifluoropropanol by reducing ethyl trifluoropropionate and the work-up procedure, wherein diisobutylaluminum hydride is a sensitive metallic reagent. The reaction is carried out by a low-temperature full-continuous reaction system, so that the heat utilization efficiency can be improved, and the reduction temperature of the diisobutylaluminum hydride for reducing the ethyl trifluoropropionate is preferably-30-0 ℃.
The working flow of the above-mentioned low-temperature full-continuous reaction system will be described below with reference to fig. 2, firstly, the raw material solution in the first raw material supply device 11 and the sensitive metal reagent in the sensitive metal reagent supply device 12 are simultaneously pumped into the low-temperature continuous reaction device 13 (i.e. the first continuous coil reactor) by the first automatic feed pump 14 and the second automatic feed pump 15, respectively, and the low-temperature continuous reaction device 13 controls the temperature of the low-temperature continuous reaction device 13 through the first temperature controller so as to ensure that the temperature required by the process is reached. The mixture from the low temperature continuous reaction apparatus 13 enters a primary quenching reaction apparatus 21, and also enters a first quenching agent for primary quenching of the excess sensitive metal agent. The primary quench reaction unit 21 ensures that the reaction is within the process temperature range by its second temperature controller. The mixture from the primary quenching reaction device 21 enters the secondary quenching reaction device 22, and simultaneously, a second quenching agent is also entered, wherein the first quenching agent and the second quenching agent can be the same and are used for further thoroughly quenching the sensitive metal reagent, and meanwhile, inorganic matters in the system are washed into an aqueous phase from a reaction organic phase, and the reaction temperature can be controlled by a third temperature controller. The system in the secondary quenching reaction device 22 is transferred to the continuous liquid separation column 31 through the fifth automatic feed pump 35 for continuous liquid separation, the lower aqueous phase continuously enters the aqueous phase storage tank, and the upper organic phase continuously enters the organic phase buffer storage tank 33. The continuous liquid separation column 31 is temperature controlled by a fourth temperature controller. The aqueous phase in the aqueous phase storage tank is continuously transferred to the continuous extraction separation column 32 by the sixth automatic feed pump 36 while the extraction solvent is pumped by the continuous pump. The temperature of the continuous extraction separation column 32 is controlled by a substrate temperature controller, and in the continuous extraction separation column 32, after the aqueous phase is further extracted, the aqueous phase continuously flows out into a waste water storage tank, and the extracted organic phase continuously enters an organic phase buffer storage tank 33. The organic phase in the organic phase buffer tank 33 is continuously transferred to the continuous drying column 41 by the seventh automatic feed pump 44, and simultaneously, the solid drying agent is continuously fed into the continuous drying column 41 by the drying agent continuous supply device 43 to dry the organic phase, and the temperature of the continuous drying column 41 is controlled by the sixth temperature controller. The water phase is formed after drying and water absorption in the continuous drying column 41, and is continuously discharged from a liquid outlet at the bottom layer of the drying column, and the organic phase is continuously discharged from a liquid outlet at the upper layer of the continuous drying column 41 and enters a storage tank for the organic phase after drying. The organic phase in the organic phase storage tank is pumped into the first continuous thin film evaporator 421 by the eighth automatic feed pump 45, and the concentration temperature thereof is controlled by the seventh temperature controller. The organic phase is concentrated by the first continuous thin film evaporator 421 and then enters the storage tank, the organic phase in the storage tank continuously enters the second continuous thin film evaporator 422 by the ninth automatic feed pump 46, and simultaneously, the azeotropic solvent is pumped into the second continuous thin film evaporator 422 by the azeotropic solvent supply device 423 through the tenth automatic feed pump 47. The second continuous thin film evaporator 422 is used for azeotropic dehydration by the entrainer, further drying the product to pass, and the concentration temperature of the second continuous thin film evaporator 422 is controlled by an eighth temperature controller. The liquid exiting the second continuous thin film evaporator 422 is the final acceptable product and is received by a receiving tank.
The advantageous effects of the present application will be further described below with reference to examples and comparative examples.
The ethyl trifluoropropionate is reduced by diisobutyl aluminum hydride to prepare trifluoropropanol, and the reaction route is as follows:
example 1
The reaction is carried out by adopting a continuous production process, wherein the continuous production process is carried out by adopting a system shown in figure 2, the molar ratio of diisobutylaluminum hydride to ethyl trifluoropropionate is 1.25, the quenching agent for the first quenching is ethanol, the dosage of the quenching agent is 5.0 equivalents, and the quenching temperature is 20 ℃; the quenching agent for the second quenching is 10% sulfuric acid water solution, the using amount of the quenching agent is 2.5 equivalents, and the quenching temperature is 20 ℃; the temperature of the first liquid separation is 20 ℃; the temperature of the extraction liquid separation is 20 ℃, the extractant is 2-methyltetrahydrofuran, and the dosage of the extractant is 5-10 mL/g relative to the ethyl trifluoropropionate; the temperature of the drying liquid is 20 ℃, the drying agent is anhydrous magnesium sulfate, and the dosage of the drying agent is 1.0g/g relative to the ethyl trifluoropropionate; the concentration temperature of the first film is 25 ℃, and the concentration vacuum degree is-0.09 MPa; the concentration temperature of the second film is 20 ℃, the concentration vacuum degree is-0.09, the entrainer is ethanol, and the consumption of the entrainer is 3g/L relative to the ethyl trifluoropropionate.
Example 2
The reaction is carried out by adopting a continuous production process, wherein the continuous production process is carried out by adopting a system shown in figure 2, the molar ratio of diisobutylaluminum hydride to ethyl trifluoropropionate is 1.05, the quenching agent for the first quenching is ethanol, the dosage of the quenching agent is 6.0 equivalents, and the quenching temperature is 0 ℃; the quenching agent for the second quenching is 10% sulfuric acid water solution, the using amount of the quenching agent is 1.5 equivalent, and the quenching temperature is 30 ℃; the temperature of the first liquid separation is 30 ℃; the temperature of the extraction liquid separation is 30 ℃, the extractant is 2-methyltetrahydrofuran, and the dosage of the extractant is 5mL/g relative to the ethyl trifluoropropionate; the temperature of the drying liquid is 10 ℃, the drying agent is anhydrous sodium sulfate, and the dosage of the drying agent is 1.5g/g relative to the ethyl trifluoropropionate; the concentration temperature of the first film is 30 ℃, and the concentration vacuum degree is-0.08 MPa; the concentration temperature of the second film is 30 ℃, the concentration vacuum degree is-0.08 MPa, the entrainer is ethanol, and the consumption of the entrainer is 1g/L relative to the ethyl trifluoropropionate.
Example 3
The reaction is carried out by adopting a continuous production process, wherein the continuous production process is carried out by adopting a system shown in figure 2, the molar ratio of diisobutylaluminum hydride to ethyl trifluoropropionate is 1.50, the quenching agent for the first quenching is ethanol, the dosage of the quenching agent is 3.0 equivalent, and the quenching temperature is 30 ℃; the quenching agent for the second quenching is 10% sulfuric acid water solution, the using amount of the quenching agent is 3.0 equivalents, and the quenching temperature is 0 ℃; the temperature of the first liquid separation is 10 ℃; the temperature of the extraction liquid is 10 ℃, the extractant is 2-methyltetrahydrofuran, and the dosage of the extractant is 10mL/g relative to the ethyl trifluoropropionate; the temperature of the drying liquid is 30 ℃, the drying agent is anhydrous potassium carbonate, and the dosage of the drying agent is 0.5g/g relative to the ethyl trifluoropropionate; the concentration temperature of the first film is 15 ℃, and the concentration vacuum degree is-0.1 MPa; the concentration temperature of the second film is 15 ℃, the concentration vacuum degree is-0.1 MPa, the entrainer is ethanol, and the consumption of the entrainer is 4g/L relative to ethyl trifluoropropionate.
Comparative example 1
The same procedure as in example 1 was carried out using a batch production process, wherein each of the other parameters was the same as in example 1 except that the reaction temperature was different.
The reaction times and temperatures for the two processes are shown in the following table:
from the comparison, the low-temperature full-continuous reaction system can improve the product yield, shorten the reaction time and improve the post-treatment efficiency relative to batch reaction.
From the above description, it can be seen that the above embodiments of the present invention achieve the following technical effects:
The low-temperature full-continuous reaction system comprises a low-temperature continuous reaction unit, namely, the low-temperature reaction is realized by utilizing a continuous reaction technology, so that the heat energy of the low-temperature reaction is effectively improved, the reaction temperature is further milder, the generation of byproducts and impurities is better controlled, and the purity and the yield of the product are improved; the material after the low-temperature reaction is subjected to continuous post-treatment by the continuous quenching unit, the continuous liquid separating unit and the continuous film concentrating unit, so that the target product obtained after the low-temperature reaction can be separated in time, the increase of byproducts caused by product accumulation is avoided, the separation efficiency and the yield of the target product are further improved, and the energy and the reagent consumed by the product purification are reduced due to the reduction of byproducts and impurities, namely, the energy consumption, the waste emission and the treatment cost of the product purification are reduced. Meanwhile, the application of the low-temperature full-continuous reaction system ensures that the equipment is simple and convenient to operate, the safety is improved, the working strength of operators is reduced, and the labor cost is also reduced.
The above description is only of the preferred embodiments of the present invention and is not intended to limit the present invention, but various modifications and variations can be made to the present invention by those skilled in the art. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (14)
1. An application of a low-temperature full-continuous reaction system in low-temperature full-continuous reaction;
The application is a reaction for preparing trifluoropropanol by reducing ethyl trifluoropropionate by diisobutyl aluminum hydride and a post-treatment process;
The low-temperature full-continuous reaction system comprises:
a low temperature continuous reaction unit (10) having a crude product system outlet;
a continuous quench unit (20) having a crude product system inlet and a quench product outlet, said crude product system outlet being connected to said crude product system inlet;
a continuous liquid separation unit (30) having a quench product inlet and a crude product outlet, the quench product outlet being connected to the quench product inlet; and
A continuous film concentration unit (40) having a crude product inlet and a product outlet, the crude product outlet being connected to the crude product inlet;
The continuous film concentration unit (40) includes:
A continuous drying column (41) having a desiccant inlet, a third organic phase outlet and the crude product inlet; a continuous thin film evaporation device (42) having a second organic phase inlet and said product outlet;
The continuous thin film evaporation device (42) comprises: a first continuous thin film evaporator (421) having the second organic phase inlet and a fourth organic phase outlet; a second continuous thin film evaporator (422) having a third organic phase inlet, an azeotropic solvent inlet and said product outlet;
the continuous quenching unit (20) comprises: a primary quench reaction device (21) having a first quench inlet, a primary quench product outlet, and said crude product system inlet;
A secondary quench reaction device (22) having a second quench inlet, a primary quench product inlet and said quench product outlet, said primary quench product outlet being connected to said primary quench product inlet;
a first quencher supply (23) connected to the first quencher inlet via a third automatic feed pump (25);
A second quencher supply (24) connected to the second quencher inlet via a fourth automatic feed pump (26);
The primary quenching reaction device (21) is a second coil reactor;
the secondary quenching reaction device (22) is a continuous reaction kettle;
The continuous liquid separation unit (30) comprises:
a continuous liquid separation column (31) having a first organic phase outlet, an aqueous phase outlet and said quench product inlet, said quench product outlet being connected to said quench product inlet by a fifth automatic feed pump (35);
A continuous extraction separation column (32) having an extractant inlet, an aqueous phase inlet, and a second organic phase outlet, the aqueous phase outlet being connected to the aqueous phase inlet by a sixth automatic feed pump (36);
An organic phase buffer storage tank (33) having a first organic phase inlet and a crude product outlet, the first organic phase outlet, the second organic phase outlet being connected to the first organic phase inlet, an extractant supply device (34) being connected to the extractant inlet;
The continuous thin film evaporation device (42) further comprises an azeotropic solvent supply device (423) connected with the azeotropic solvent inlet through a tenth automatic feed pump (47);
the low-temperature continuous reaction unit (10) comprises: a first raw material supply device (11); a sensitive metal reagent supply device (12);
The low-temperature continuous reaction device (13) is provided with a first raw material inlet, a sensitive metal reagent inlet and a crude product system outlet, the first raw material supply device (11) is connected with the first raw material inlet through a first automatic feed pump (14), and the sensitive metal reagent supply device (12) is connected with the sensitive metal reagent inlet through a second automatic feed pump (15).
2. The use of claim 1, wherein the second coil reactor has a second temperature controller.
3. The use according to claim 1, wherein the continuous reactor is provided with a third temperature controller.
4. Use according to claim 1, wherein the continuous liquid separation column (31) has a fourth temperature controller.
5. Use according to claim 1, characterized in that the continuous extraction separation column (32) has a fifth temperature controller.
6. The use according to claim 1, wherein the continuous film concentration unit (40) further comprises: the crude product outlet is connected to the crude product inlet by a seventh automatic feed pump (44);
The third organic phase outlet is connected with the second organic phase inlet through an eighth automatic feed pump (45).
7. Use according to claim 1, wherein the continuous film concentration unit (40) further comprises a continuous supply of desiccant (43), the continuous supply of desiccant (43) being connected to the desiccant inlet.
8. Use according to claim 7, wherein the continuous supply of desiccant (43) is a screw feeder.
9. Use according to claim 1, wherein the continuous drying column (41) has a sixth temperature controller.
10. Use according to claim 1, wherein in the continuous thin film evaporation device (42) the fourth organic phase outlet is connected to the third organic phase inlet by a ninth automatic feed pump (46).
11. Use according to claim 1, wherein the first continuous thin film evaporator (421) has a seventh temperature controller and the second continuous thin film evaporator (422) has an eighth temperature controller.
12. Use according to claim 1, characterized in that the low-temperature continuous reaction device (13) is a first coil reactor.
13. The use according to claim 12, wherein the first coil reactor has a first temperature controller.
14. The use according to claim 1, wherein the reduction temperature of the diisobutylaluminum hydride for reducing ethyl trifluoropropionate is-30-0 ℃.
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