CN208869523U - Prepare the continuous device of benzaldehydes intermediate - Google Patents
Prepare the continuous device of benzaldehydes intermediate Download PDFInfo
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- CN208869523U CN208869523U CN201821430923.0U CN201821430923U CN208869523U CN 208869523 U CN208869523 U CN 208869523U CN 201821430923 U CN201821430923 U CN 201821430923U CN 208869523 U CN208869523 U CN 208869523U
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Abstract
The utility model provides a kind of continuous device for preparing benzaldehydes intermediate.The continuous device includes continuous lithiation device and continuous formylated device.Continuous lithiation device is provided with first charging aperture and the first discharge port, and first charging aperture is for being added reaction raw materials and organolithium reagent, and the first discharge port is for the product system of continuous lithiation to be continuously discharged；Continuous formylated device is provided with second charging aperture, formylation reagent entrance and the second discharge port; second charging aperture is connected with the first discharge port; so that the product system of continuous lithiation is continuously delivered in continuous formylated device; formylation reagent entrance is for being added formylation reagent, and the second discharge port is for the product system of continuous formylation reaction to be continuously discharged.Be conducive to improve reaction selectivity using above-mentioned apparatus, reduce energy consumption, while being also convenient for carrying out industrialized production.
Description
Technical field
The utility model relates to the synthesis fields of medicine intermediate, prepare among benzaldehydes in particular to a kind of
The continuous device of body.
Background technique
Benzaldehydes intermediate is a kind of common and very important medicine intermediate.Its synthetic method has very much, mainly
Aldehyde radical on carbonyl method and low temperature lithiation is directly inserted in Wei Er David Smail reaction formylated method, phenyl ring including toluene oxidation method, aromatic ring
Method etc..Wherein aldehyde radical is a kind of very classical synthetic method on low temperature lithiation, and it is very good to be formed with other synthetic methods
Complementation.
Using traditional batch reaction process, the process of aldehyde radical method is as follows on low temperature lithiation: raw material and solvent are added to
In reactor, it is stirred dissolution under nitrogen protection.Then material solution is cooled to -78 under the protection of inert gas again
℃.Lithium diisopropylamine solution is added dropwise into reaction system at -78 DEG C for temperature control simultaneously.After being added dropwise, reaction system is protected
0.5~1.5h of temperature stirring.The temperature of reaction system is continued into control extremely at -78 DEG C, and N, N- dimethyl will be added dropwise in reaction system
Formamide.After being added dropwise, architecture heat preservation stirs 10min.Then acid solution is added dropwise system is quenched.
When carrying out low temperature lithiation reaction using traditional batch reaction process, usually have the disadvantage in that
1. needing low-down reaction temperature, energy consumption is larger, at high cost.The batch as disclosed in existing literature reacts low
In warm lithiation process, reaction temperature usually requires control to -70 DEG C or less.
2. batch reaction is complete mixing flow reactive mode, the high activity lithium salts intermediate that this mode can be such that reaction process generates
Uniform or approaches uniformity to be scattered in reaction system, this is very unfavorable for the substrate in structure containing reactive group, and height is living
Property lithium salts intermediate can and structure in reactive group reaction, thus make reaction selectivity be deteriorated, lead to main reaction yield
And system purity is very low.
3. enlarge-effect is obvious, technique is not easy to amplify.Aldehyde radical reacts on low temperature lithiation, and usual exothermic heat of reaction amount is very big.Make
It is amplified with the low batch reaction kettle of mass-transfer efficiency and heat transfer efficiency, will lead to serious enlarge-effect.To make purity
And yield declines to a great extent.And after technique amplification, for control system temperature, the drop rate of material is usually controlled very slow,
This not only declines production efficiency, but also increases the risk of each material deterioration in reaction system.
Utility model content
The main purpose of the utility model is to provide a kind of continuous devices for preparing benzaldehydes intermediate, to solve
The existing batch method for preparing benzaldehyde there is a problem of severe reaction conditions and reaction selectivity difference.
To achieve the goals above, one aspect according to the present utility model provides a kind of prepare among benzaldehydes
The continuous device of body, continuous device include continuous lithiation device and continuous formylated device.Continuous lithiation dress
It installs and is equipped with first charging aperture and the first discharge port, for reaction raw materials and organolithium reagent to be added, first goes out first charging aperture
Material mouth is for the product system of continuous lithiation to be continuously discharged；Continuous formylated device is provided with second charging aperture, formyl
Change reagent inlet and the second discharge port, second charging aperture are connected with the first discharge port, so that the product body of continuous lithiation
System is continuously delivered in continuous formylated device, and formylation reagent entrance is used for formylation reagent, the second discharge port to be added
It is continuously discharged in by the product system of continuous formylation reaction.
Further, continuous device further includes that device is continuously quenched, be continuously quenched device be provided with third feed inlet and
Quencher entrance, third feed inlet are connected with the second discharge port and are used for the product system of continuous formylation reaction continuously
It is delivered to and device is continuously quenched, quencher entrance is for being added quencher.
Further, it continuous lithiation device, continuous formylated device and continuously device is quenched separately is selected from
Continuous coil pipe reaction unit continuously stirs autoclave reaction unit.
Further, continuous device further includes that temperature control is bathed outside the first pre-cooler, the second pre-cooler and the first collet
Device, the first pre-cooler are provided with reaction raw materials entrance and the outlet of pre-cooling material liquid；Second pre-cooler is provided with organolithium
Reagent inlet and the outlet of pre-cooling organolithium reagent；Temperature regulating device is bathed outside first collet for controlling the first pre-cooler and second in advance
The temperature of device for cooling；The outlet of pre-cooling material liquid and the outlet of pre-cooling organolithium reagent are connected with first charging aperture, so that pre-cooling
Material liquid and pre-cooling organolithium reagent are continuously delivered to continuous lithiation device.
Further, continuous device further includes formylation reagent feeding mechanism and the first delivery pump.Formylation reagent supplies
Device is answered to be provided with formylation reagent supply opening, formylation reagent supply opening is connected with formylation reagent entrance, is used for first
Acylating reagent is continuously conveyed into continuous formylated device；The setting of first delivery pump is tried in formylation reagent supply opening and formylated
On flow path between agent entrance.
Further, continuous device further includes that temperature regulating device is bathed outside third pre-cooler and the second collet.Along formylated
The downstream of the first delivery pump is arranged in the flow direction of reagent, third pre-cooler；And second bathe temperature regulating device outside collet and be used for
Control the temperature in third pre-cooler.
Further, continuous device further includes raw material liquid supply unit and the second delivery pump, and raw material liquid supply unit is set
It is equipped with material liquid supply opening, material liquid supply opening is connected with reaction raw materials entrance, is used for continuously into the first pre-cooler
Transferring raw material liquid；Second delivery pump is arranged on the flow path between material liquid supply opening and reaction raw materials entrance.
Further, continuous device further includes organolithium reagent feeding mechanism and third delivery pump, and organolithium reagent supplies
Device is answered to be provided with organolithium reagent supply opening, organolithium reagent supply opening is connected with organolithium reagent entrance, organolithium examination
Agent feeding mechanism is for continuously conveying organolithium reagent into the second pre-cooler；Third delivery pump is arranged in organolithium reagent
On flow path between supply opening and organolithium reagent entrance.
Further, continuous device further includes quencher feeding mechanism and the 4th conveying device, quencher feeding mechanism
It is provided with quencher supply opening, quencher supply opening is connected with quencher entrance, for continuously to being continuously quenched in device
Convey quencher；4th conveying device is arranged on the flow path between quencher supply opening and quencher entrance.
Further, continuous device further includes bathing temperature regulating device outside the 4th pre-cooler and third collet, along quencher
Flow direction, the downstream of the 4th conveying device is arranged in the 4th pre-cooler；And temperature regulating device is bathed outside third collet for controlling
Make the temperature in the 4th pre-cooler.
Further, the first pre-cooler, the second pre-cooler, third pre-cooler and the 4th pre-cooler be independently
Ground is selected from continuous coil pipe reaction unit or continuously stirs autoclave reaction unit.
Using the technical solution of the utility model, conventional batch reactor, continuous reaction dress provided by the present application are compared
The specific surface area set is bigger；And due to being continuous flow process, working volume is more much smaller than conventional batch reactor, passes simultaneously
Matter coefficient and heat transfer coefficient are higher.This makes the reaction temperature of continuous flow process higher (more mild), so as to reduce energy
Consumption.The raising of reaction temperature makes reaction rate faster again, and the reaction time is shorter, this advantageously reduces the risk of side reaction, improves
Reaction selectivity.Simultaneously in continuous reacting device provided by the present application, reaction raw materials are continuously inputted, and reaction product is continuous
Discharge, this is also beneficial to the generation for reducing side reaction, improves the selectivity of reaction.Furthermore the technique is substantially without enlarge-effect, this
So that the amplification metaplasia production of the technique is more easier.
Detailed description of the invention
The accompanying drawings constituting a part of this application is used to provide a further understanding of the present invention, this is practical
Novel illustrative embodiments and their description are not constituteed improper limits to the present invention for explaining the utility model.
In the accompanying drawings:
Fig. 1 shows aldehyde in the use continuous low temperature lithiumation that a kind of preferred embodiment according to the present utility model provides
Base method prepares the structural schematic diagram of the continuous device of benzaldehydes intermediate.
Wherein, the above drawings include the following reference numerals:
10, continuous lithiation device；11, raw material liquid supply unit；12, the second delivery pump；13, organolithium reagent is supplied
Device；14, third delivery pump；101, first charging aperture；102, the first discharge port；20, continuous formylated device；21, formylated
Agent delivery device；22, the first delivery pump；201, second charging aperture；202, formylation reagent entrance；203, the second discharge port；
30, device is continuously quenched；31, quencher feeding mechanism；32, the 4th conveying device；301, third feed inlet；302, quencher enters
Mouthful；40, the first pre-cooler；41, temperature regulating device is bathed outside the first collet；401, reaction raw materials entrance；402, pre-cooling material liquid goes out
Mouthful；50, the second pre-cooler；501, organolithium reagent entrance；502, pre-cooling organolithium reagent outlet；60, third pre-cooler；
61, temperature regulating device is bathed outside the second collet；70, the 4th pre-cooler；71, temperature regulating device is bathed outside third collet.
Specific embodiment
It should be noted that in the absence of conflict, the features in the embodiments and the embodiments of the present application can phase
Mutually combination.The utility model is described in detail below in conjunction with embodiment.
As described in background technique, the existing batch method for preparing benzaldehyde is there are severe reaction conditions and instead
The problem of answering poor selectivity.In order to solve the above-mentioned technical problem, this application provides a kind of using aldehyde radical in continuous low temperature lithiumation
Method prepares the continuous device of benzaldehydes intermediate, as shown in Figure 1, the continuous device includes continuous lithiation device 10
With continuous formylated device 20, continuous lithiation device 10 is provided with first charging aperture 101 and the first discharge port 102, and first
Feed inlet 101 is used for for reaction raw materials and organolithium reagent, the first discharge port 102 to be added by the product body of continuous lithiation
The continuous discharge of system；Continuous formylated device 20 is provided with second charging aperture 201, formylation reagent entrance 202 and the second discharge port
203, second charging aperture 201 is connected with the first discharge port 102, so that the product system of continuous lithiation is continuously delivered to
In continuous formylated device 20, formylation reagent entrance 202 is for being added formylation reagent, and the second discharge port 203 will be for that will connect
The product system of continuous formylation reaction is continuously discharged.
Compared to conventional batch reactor, the specific surface area of continuous reacting device provided by the present application is bigger；And due to being
Continuous flow process, working volume is more much smaller than conventional batch reactor, while mass tranfer coefficient and heat transfer coefficient are higher.This makes
The reaction temperature for obtaining continuous flow process is higher (more mild), so as to reduce energy consumption.The raising of reaction temperature makes to react again
Faster, the reaction time is shorter for rate, this advantageously reduces the risk of side reaction, improves reaction selectivity.It is mentioned simultaneously in the application
In the continuous reacting device of confession, reaction raw materials are continuously inputted, and reaction product is continuously discharged, this is also beneficial to reduce side reaction
Generation, improve the selectivity of reaction.Furthermore for the technique substantially without enlarge-effect, this produces the amplification metaplasia of the technique more
It is easy.
Some materials with reactivity would generally be remained in the product system of continuous formylation reaction, this will affect work
The safety of skill.In order to improve the safety of technique, in a preferred embodiment, as shown in Figure 1, the continuous device
Further include that device 30 is continuously quenched, device 30 be continuously quenched and is provided with third feed inlet 301 and quencher entrance 302, third into
Material mouth 301 is connected with the second discharge port 203 for the product system of continuous formylation reaction to be continuously delivered to continuously quench
Go out device 30, and quencher entrance 302 is for being added quencher.Quenching reaction is carried out using device 30 is continuously quenched, it can be continuous
The product system of continuous formylation reaction is quenched online on ground, moreover it is possible to benzaldehydes intermediate continuously be discharged, this is in pole
The ratio that by-product is reduced in big degree improves the selectivity of reaction, while being quenched also greatly enhance online
The safety of reaction.
In a preferred embodiment, it continuous lithiation device 10, continuous formylated device 20 and is continuously quenched
Device 30 separately selected from continuous coil pipe reaction unit or continuously stirs autoclave reaction unit.
In above-mentioned continuous process, either continuous coil reactor or continuous stirred tank reactor have
Fresh raw material constantly flows into reactor, meanwhile, the system after reaction is constantly flowed out from reactor outlet.This is conducive to further
Complicated side reaction between the product, intermediate and the raw material that inhibit reaction to generate, promotes reaction selectivity and yield.
In a preferred embodiment, as shown in Figure 1, the continuous device further includes the first pre-cooler 40,
Bathe temperature regulating device 41 outside two pre-coolers 50 and the first collet, the first pre-cooler 40 is provided with reaction raw materials entrance 401 and pre-
Cold material liquid outlet 402；Second pre-cooler 50 is provided with organolithium reagent entrance 501 and pre-cooling organolithium reagent outlet 502,
Pre-cooling material liquid outlet 402 and pre-cooling organolithium reagent outlet 502 are connected with first charging aperture 101, so that pre-cooling raw material
Liquid and pre-cooling organolithium reagent are continuously delivered to continuous lithiation device 10, and temperature regulating device 41 is bathed outside the first collet for controlling
Make the temperature of the first pre-cooler 40 and the second pre-cooler 50.
Bath temperature regulating device 41 outside the first pre-cooler 40, the second pre-cooler 50 and the first collet, which will be arranged, will react
Material liquid and lithiation reagent are delivered to before continuous lithiation device 10, first by its it is pre- be cooled to assigned temperature, this is conducive to press down
Preparing high-temp feed liquid mixes significantling change for caused system temperature with low-temp reaction system, and then is conducive to inhibit side reaction
Occur.
In a preferred embodiment, as shown in Figure 1, the continuous device further includes formylation reagent feeding mechanism
21 and first delivery pump 22, formylation reagent feeding mechanism 21 be provided with formylation reagent supply opening, formylation reagent supply opening
It is connected with formylation reagent entrance 202, for being continuously conveyed formylation reagent into continuous formylated device 20；First is defeated
Pump 22 is sent to be arranged on the flow path between formylation reagent supply opening and formylation reagent entrance 202.
The setting of formylation reagent feeding mechanism 21 and the first delivery pump 22 can be such that it continuously disguises to continuous formyl
It sets and formylation reagent is added in 20, this is conducive to the continuity for improving continuous formylation reaction, the labor intensity of operator is reduced,
Improve the selectivity of reaction.
In a preferred embodiment, as shown in Figure 1, the continuous device further includes third pre-cooler 60 and
Temperature regulating device 61 is bathed outside two collets, along the flow direction of formylation reagent, third pre-cooler 60 is arranged in the first delivery pump 22
Downstream；Temperature regulating device 61 is bathed outside second collet to be used to control the temperature in third pre-cooler 60.Third pre-cooler is set
60 and second bathe temperature regulating device 61 outside collet formylation reagent can be made to be pre-chilled before entering continuous formylated device 20,
And then be conducive to reduce the temperature difference between formylation reagent and the product system of continuous lithiation, reduce temperature fluctuation, into
And be conducive to further suppress the generation of side reaction.
In a preferred embodiment, as shown in Figure 1, the continuous device further includes 11 He of raw material liquid supply unit
Second delivery pump 12, raw material liquid supply unit 11 are provided with material liquid supply opening, material liquid supply opening and reaction raw materials entrance 401
It is connected, for the continuously transferring raw material liquid into the first pre-cooler 40；Second delivery pump 12 is arranged in material liquid supply opening
On flow path between reaction raw materials entrance 401.
In a preferred embodiment, as shown in Figure 1, the continuous device further includes organolithium reagent feeding mechanism
13 and third delivery pump 14, organolithium reagent feeding mechanism 13 be provided with organolithium reagent supply opening, organolithium reagent supply opening
It is connected with organolithium reagent entrance 501, for continuously conveying organolithium reagent into the second pre-cooler 50；Third conveying
Pump 14 is arranged on the flow path between organolithium reagent supply opening and organolithium reagent entrance 501.
The setting of raw material liquid supply unit 11 and the second delivery pump 12 and organolithium reagent feeding mechanism 13 and third are defeated
Send the setting of pump 14 that can make it that reaction raw materials and organolithium reagent continuously be added into continuous formylated device 20, this is advantageous
In the continuity for improving continuous lithiation, the labor intensity of operator is reduced, the selectivity of reaction is improved.
In a preferred embodiment, as shown in Figure 1, the continuous device further includes 31 He of quencher feeding mechanism
4th conveying device 32, quencher feeding mechanism 31 are provided with quencher supply opening, quencher supply opening and quencher entrance 302
It is connected, for continuously conveying quencher to continuous be quenched in device 30；The setting of 4th conveying device 32 is supplied in quencher
On flow path between mouth and quencher entrance 302.
The setting of quencher feeding mechanism 31 and the 4th conveying device 32 can make it that device 30 continuously be quenched to continuous
Middle addition quencher, this is conducive to improve the continuity being quenched, reduces the labor intensity of operator, improve the selectivity of reaction.
In a preferred embodiment, as shown in Figure 1, the continuous device further includes the 4th pre-cooler 70 and
Temperature regulating device 71 is bathed outside three collets, along the flow direction of quencher, the 4th conveying device 32 is arranged in the 4th pre-cooler 70
Downstream, third collet bathe temperature regulating device 71 outside and are used to control the temperature in the 4th pre-cooler 70.4th pre-cooler 70 is set
Quencher can be made to be pre-chilled into before device 30 continuously is quenched with temperature regulating device 71 is bathed outside third collet, and then advantageous
In reducing the temperature difference between quencher and the product system of continuous formylation reaction, reduce temperature fluctuation, so be conducive into
The generation of one step inhibition side reaction.
Material to be pre-chilled can be made continuously to be pre-chilled using the pre-cooler of serialization, this is conducive to improve reaction
Selectivity and yield, it is highly preferred that the first pre-cooler 40, the second pre-cooler 50, third pre-cooler 60 and the 4th pre-cooling
Device 70 separately selected from continuous coil pipe reaction unit or continuously stirs autoclave reaction unit.
The another aspect of the application additionally provides aldehyde radical method in a kind of continuous low temperature lithiumation and is preparing benzaldehydes intermediate
In application, prepared using above-mentioned continuous device, which includes: continuously to convey material liquid and organolithium reagent
Continuous lithiation is carried out into continuous lithiation device 10, lithiated product is obtained, continuously lithiated product is discharged；By lithium
Change product and formylation reagent to be continuously delivered to carry out continuous formylation reaction, obtain benzaldehydes intermediate, and by benzene first
Aldehydes intermediate is continuously discharged.
Compared to conventional batch reactor, the specific surface area of continuous reacting device provided by the present application is bigger；And due to being
Continuous flow process, working volume is more much smaller than conventional batch reactor, while mass tranfer coefficient and heat transfer coefficient are higher.This makes
The reaction temperature for obtaining continuous flow process is higher (more mild), so as to reduce energy consumption.The raising of reaction temperature makes to react again
Faster, the reaction time is shorter for rate, this advantageously reduces the risk of side reaction, improves reaction selectivity.It is mentioned simultaneously in the application
In the continuous reacting device of confession, reaction raw materials are continuously inputted, and reaction product is continuously discharged, this is also beneficial to reduce side reaction
Generation, improve the selectivity of reaction.Furthermore for the technique substantially without enlarge-effect, this produces the amplification metaplasia of the technique more
It is easy.On this basis, be conducive to improve the temperature, anti-of reaction when preparing benzaldehydes intermediate using above-mentioned continuous device
The yield of the selectivity and product answered.
In order to reduce influence of the extraneous factor to product yield, it is preferable that before carrying out continuous reaction, use inertia
Gas or nitrogen replace the gas in continuous reacting device.Inert gas is provided by inert gas feeding mechanism.
In a preferred embodiment, the reaction temperature of continuous lithiation is -80~-30 DEG C, the reaction time 1
~30min.The reaction temperature of continuous lithiation and reaction time include but is not limited to above range, and are limited to above-mentioned
Be conducive to further increase the yield of continuous lithiation in range.It is highly preferred that the reaction temperature of continuous lithiation is -60
~-50 DEG C, the reaction time is 5~10min.
In a preferred embodiment, the reaction temperature of continuous formylation reaction is -80~-30 DEG C, the reaction time
For 1~30min.The reaction temperature of continuous formylation reaction and reaction time include but is not limited to above range, and are limited
Be conducive to further increase the yield of continuous lithiation within the above range.It is highly preferred that the reaction of continuous formylation reaction
Temperature is -50~-40 DEG C, and the reaction time is 5~10min.
In a preferred embodiment, above-mentioned application further include: the product system of continuous formylation reaction is continuous
Ground, which is delivered to continuously to be quenched in device 30, carries out continuous quenching reaction, obtains benzaldehydes intermediate using continuous and device 30 is quenched
Quenching reaction is carried out, continuously the product system of continuous formylation reaction can be quenched online, moreover it is possible to continuously be discharged
Benzaldehydes intermediate, this largely reduces the ratio of by-product, improves the selectivity of reaction, while quenching online
It goes out and also greatly enhances the safety of reaction.
The application is described in further detail below in conjunction with specific embodiment, these embodiments should not be understood as limitation originally
Apply for range claimed.
Embodiment 1
Benzaldehydes intermediate is prepared using device as shown in Figure 1, concrete operations process is as follows:
By the bromo- 4- fluorobenzaldehyde tert-butyl ester tetrahydrofuran solution of the 2- prepared (1.0 equivalent) by raw material liquid supply unit 11
Output, is delivered in the continuous coil reactor of the first pre-cooler 40, by lithium diisopropylamine (1.1 through the second delivery pump 12
Equivalent) by organolithium reagent feeding mechanism 13 second pre-cooler 50 is delivered to by third delivery pump 14, and outside the first collet
Temperature control is carried out under the action of bath temperature regulating device 41.Material solution and organolithium reagent solution after pre-cooled is in continuous lithiation
The continuous lithiation that the first stage is mixed and carried out in device 10, obtains lithiated product.In reaction process, material solution and have
Machine lithium reagent solution continuously inputs in continuous lithiation device 10 through first charging aperture 101, after continuous lithiation
Product system is continuously discharged from the first discharge port 102, and is continuously delivered to continuous formylated device through second charging aperture 201
In 20.
The formylation reagent (2.0 equivalent) supplied by formylation reagent feeding mechanism 21 is delivered to through the first delivery pump 22
In three pre-coolers 60, it is pre-chilled under the action of temperature regulating device 61 are bathed outside the second collet, is then connected through second charging aperture 201
It is delivered in continuous formylated device 20 continuously, carries out continuous formylation reaction with the product system of continuous lithiation.Reaction
Product system afterwards is continuously delivered to continuously be quenched instead again through the second continuously discharge of discharge port 203 through third feed inlet 301
It answers in device.The quencher (acetic acid, 3.0 equivalents) provided by quencher feeding mechanism 31 is continuously defeated through the 4th conveying device 32
It send into the 4th pre-cooler 70, is pre-chilled under the action of temperature regulating device 71 are bathed outside third collet.It then will be after pre-cooling
Quencher, which is continuously delivered to continuously be quenched in device 30, carries out continuous quenching reaction.System after being quenched continuously is discharged, and carries out
Subsequent post-processing obtains required benzaldehydes intermediate.Parameter in reaction is shown in Table 1.
Synthetic route are as follows:
Embodiment 2
With the difference of embodiment 1 are as follows: the reaction temperature of continuous lithiation is -20 DEG C and the reaction time is 40min.
Embodiment 3
With the difference of embodiment 1 are as follows: the reaction temperature of continuous formylation reaction is -20 DEG C and the reaction time is 40min.
Comparative example 1
With the difference of embodiment 1 are as follows: prepare benzaldehydes intermediate using batch technique, reaction unit is intermittent anti-
Answer kettle.
Table 1
It can be seen from the above description that the above embodiments of the utility model achieve the following technical effects: comparing
Conventional batch reaction, using the receipts provided by the present application for being continuously synthesizing to method and being conducive to greatly improve benzaldehydes intermediate
Rate.
The above descriptions are merely preferred embodiments of the present invention, is not intended to limit the utility model, for this
For the technical staff in field, various modifications and changes may be made to the present invention.It is all in the spirit and principles of the utility model
Within, any modification, equivalent replacement, improvement and so on should be included within the scope of protection of this utility model.
Claims (11)
1. a kind of continuous device for preparing benzaldehydes intermediate, which is characterized in that the continuous device includes:
Continuous lithiation device (10), the continuous lithiation device (10) are provided with first charging aperture (101) and first
Discharge port (102), the first charging aperture (101) is for being added reaction raw materials and organolithium reagent, first discharge port
(102) for the product system of continuous lithiation to be continuously discharged；
Continuous formylated device (20), the continuous formylated device (20) are provided with second charging aperture (201), formylation reagent
Entrance (202) and the second discharge port (203), the second charging aperture (201) are connected with first discharge port (102), with
It is continuously delivered to the product system of the continuous lithiation in the continuous formylated device (20), the formylated examination
Agent entrance (202) is used for for formylation reagent, second discharge port (203) to be added by the product body of continuous formylation reaction
The continuous discharge of system.
2. continuous device according to claim 1, which is characterized in that the continuous device further includes that dress is continuously quenched
Set (30), it is described device (30) continuously is quenched to be provided with third feed inlet (301) and quencher entrance (302), the third into
Material mouth (301) is connected with second discharge port (203) and for the product system of the continuous formylation reaction is continuous
Ground be delivered to it is described be continuously quenched device (30), the quencher entrance (302) is for being added quencher.
3. continuous device according to claim 2, which is characterized in that the continuous lithiation device (10), described
Continuous formylated device (20) and the device (30) that is continuously quenched separately are selected from continuous coil pipe reaction unit or continuous
Stir kettle reactor.
4. continuous device according to claim 2 or 3, which is characterized in that the continuous device further include:
First pre-cooler (40), first pre-cooler (40) are provided with reaction raw materials entrance (401) and pre-cooling material liquid
It exports (402)；
Second pre-cooler (50), second pre-cooler (50) is provided with organolithium reagent entrance (501) and pre-cooling is organic
Lithium reagent exports (502)；
It is bathed temperature regulating device (41) outside first collet, temperature regulating device (41) is bathed outside first collet for controlling first pre-cooling
The temperature of device (40) and second pre-cooler (50)；
Pre-cooling material liquid outlet (402) and the pre-cooling organolithium reagent export (502) with the first charging aperture
(101) it is connected, so that pre-cooling material liquid and pre-cooling organolithium reagent are continuously delivered to the continuous lithiation device
(10)。
5. continuous device according to claim 4, which is characterized in that the continuous device further include:
Formylation reagent feeding mechanism (21), the formylation reagent feeding mechanism (21) are provided with formylation reagent supply opening,
The formylation reagent supply opening is connected with the formylation reagent entrance (202), for the formylation reagent is continuous
It is delivered in the continuous formylated device (20)；
First delivery pump (22), the first delivery pump (22) setting are tried in the formylation reagent supply opening and the formylated
On flow path between agent entrance (202).
6. continuous device according to claim 5, which is characterized in that the continuous device further include:
Third pre-cooler (60), along the flow direction of the formylation reagent, the third pre-cooler (60) is arranged in institute
State the downstream of the first delivery pump (22)；And
It is bathed temperature regulating device (61) outside second collet, temperature regulating device (61) is bathed outside second collet for controlling the third pre-cooling
Temperature in device (60).
7. continuous device according to claim 6, which is characterized in that the continuous device further include:
Raw material liquid supply unit (11), the raw material liquid supply unit (11) are provided with material liquid supply opening, and the material liquid supplies
Mouth is answered to be connected with the reaction raw materials entrance (401), for the continuously transferring raw material into first pre-cooler (40)
Liquid；
Second delivery pump (12), second delivery pump (12) are arranged in the material liquid supply opening and the reaction raw materials entrance
(401) on the flow path between.
8. continuous device according to claim 7, which is characterized in that the continuous device further include:
Organolithium reagent feeding mechanism (13), the organolithium reagent feeding mechanism (13) are provided with organolithium reagent supply opening,
The organolithium reagent supply opening is connected with the organolithium reagent entrance (501), and organolithium reagent feeding mechanism (13) is used
In the continuously conveying organolithium reagent into second pre-cooler (50)；
Third delivery pump (14), third delivery pump (14) setting are tried in the organolithium reagent supply opening and the organolithium
On flow path between agent entrance (501).
9. continuous device according to claim 8, which is characterized in that the continuous device further include:
Quencher feeding mechanism (31), the quencher feeding mechanism (31) are provided with quencher supply opening, and the quencher supplies
Mouth is answered to be connected with the quencher entrance (302), for continuously conveying quencher to described be continuously quenched in device (30)；
4th conveying device (32), the 4th conveying device (32) setting enter in the quencher supply opening with the quencher
On flow path between mouth (302).
10. continuous device according to claim 9, which is characterized in that the continuous device further include:
4th pre-cooler (70), along the flow direction of the quencher, the 4th pre-cooler (70) setting is described the
The downstream of four conveying devices (32)；And
It is bathed temperature regulating device (71) outside third collet, temperature regulating device (71) is bathed outside the third collet for controlling the 4th pre-cooling
Temperature in device (70).
11. continuous device according to claim 10, which is characterized in that first pre-cooler (40), described
Two pre-coolers (50), the third pre-cooler (60) and the 4th pre-cooler (70) are separately selected from continuous disk
Tube reaction device continuously stirs autoclave reaction unit.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108892616A (en) * | 2018-08-31 | 2018-11-27 | 凯莱英生命科学技术(天津)有限公司 | Prepare continuous device and its application of benzaldehydes intermediate |
| CN110386864A (en) * | 2019-08-15 | 2019-10-29 | 天津凯莱英制药有限公司 | The method for continuously synthesizing of 2,4,6- trifluro benzaldehydes |
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2018
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108892616A (en) * | 2018-08-31 | 2018-11-27 | 凯莱英生命科学技术(天津)有限公司 | Prepare continuous device and its application of benzaldehydes intermediate |
| CN108892616B (en) * | 2018-08-31 | 2024-06-07 | 凯莱英生命科学技术(天津)有限公司 | Continuous device for preparing benzaldehyde intermediate and application thereof |
| CN110386864A (en) * | 2019-08-15 | 2019-10-29 | 天津凯莱英制药有限公司 | The method for continuously synthesizing of 2,4,6- trifluro benzaldehydes |
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