CN106748686A - A kind of method that toluene fluoride continuous oxidation prepares 4-Fluorobenzaldehyde - Google Patents
A kind of method that toluene fluoride continuous oxidation prepares 4-Fluorobenzaldehyde Download PDFInfo
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- CN106748686A CN106748686A CN201610972080.6A CN201610972080A CN106748686A CN 106748686 A CN106748686 A CN 106748686A CN 201610972080 A CN201610972080 A CN 201610972080A CN 106748686 A CN106748686 A CN 106748686A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
- C07C45/28—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation of CHx-moieties
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- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/24—Stationary reactors without moving elements inside
- B01J19/2415—Tubular reactors
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/24—Stationary reactors without moving elements inside
- B01J2219/2401—Reactors comprising multiple separate flow channels
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Abstract
The method that a kind of toluene fluoride continuous oxidation of the present invention prepares 4-Fluorobenzaldehyde, belongs to organic synthesis technology field.The method is that, with p-fluorotoluene compound as raw material, one or more metal ion complexs of cobalt, molybdenum, bromine are catalyst, and hydrogen peroxide is oxidant, and acetic acid is solvent, the continuous technology that p-fluorotoluene oxidation is prepared 4-Fluorobenzaldehyde in tubular reactor.This method mild condition, the reaction time is short, and raw material availability is high, is capable of achieving the effective control in course of reaction, and safety and stability, continuous operation, production efficiency is high.
Description
Technical field
The invention belongs to organic synthesis technology field, it is related to a kind of continuous by p-fluorotoluene under liquid-phase reaction condition
The method that oxidation prepares 4-Fluorobenzaldehyde, be more specifically that, with p-fluorotoluene as substrate, hydrogen peroxide is oxidant, cobalt, molybdenum, bromine
One or more metal ion complexs are catalyst, and monocarboxylic acid is solvent, in the tubular reactor with different micro-structurals
In continuously prepare 4-Fluorobenzaldehyde product.
Background technology
4-Fluorobenzaldehyde (abbreviation PFDA) is a kind of important organic synthesis intermediate, can be used for medicine, agricultural chemicals and dyestuff
Deng synthesis, also can be used as cosmetics and plastic additive and plant protection product, bactericide, deodorant etc..It can be used to synthesize
Treat medicine haloperole, the droperidol of the nervous system disease, blood lipid-lowering medicine Rosuvastatin, Lipitor etc..Additionally, right
Fluorobenzaldehyde can be additionally used in synthesis actasal, anticarcinogen and loosening all muscles medicine etc..
The synthetically produced method of current 4-Fluorobenzaldehyde mainly includes following several：P-fluorotoluene oxidizing process, to fluorobenzene
Methyl alcohol or para-fluorophenylacetic acid oxidizing process, to fluorobenzonitrile reducing process etc., the intermediate that is used by these methods is unstable, raw material
The hydrogen fluoride reason such as have severe toxicity, synthesis step many, is not suitable for large-scale industrial production.
The commercial synthesis method of current 4-Fluorobenzaldehyde has following several：
(1) direct electrolytic oxidation method
In undivided cell, with carbon-point as electrode, methanol/ethanol is solvent to Japanese Nishiguchi etc., from spy
The electrolyte of matter, uses acid-catalyzed hydrolysis after electrolytic oxidation, corresponding aromatic aldehyde is obtained final product, wherein directly aoxidizing p-fluorotoluene on electrode
4-Fluorobenzaldehyde is prepared, yield is 73% or so.The shortcoming of the method is because organic matter will pass through the anti-of complexity on electrode
Process is answered, while oily organic matter is easily adsorbed in electrolysis on electrode, the carrying out of electrolysis is influenceed, current efficiency is dropped significantly
It is low, or even be electrolysed and cannot go on, so industrial production also acquires a certain degree of difficulty at present.
(2) indirect electrolytic oxidation method
Kumai Seisaku in 1991 et al. work out the method that oxidation p-fluorotoluene prepares 4-Fluorobenzaldehyde, i.e., in chain
In the alkyl sulfonic acid aqueous solution, electrolytic oxidation cerous acetate or cerous carbonate etc. Ce (III) salt obtains Ce (IV) salt, electrolytic cell perfluorinated ion
Exchange membrane separates, anode Pt, PbO2, Ti etc., negative electrode Pt, Ni, stainless steel etc..Ce (IV) salt that electrolysis is obtained is in reactor
In p-fluorotoluene is oxidized to 4-Fluorobenzaldehyde purity high, but its technique and equipment requirement are high, and technical difficulty is big, and cerium salt is not
It is easy to get to realization industrialization still acquires a certain degree of difficulty.
(3) p-fluorotoluene oxidizing process
The research such as Borchert Holger aoxidizes p-fluorotoluene steam and is prepared for fluorine by oxygen under catalysts conditions
Benzaldehyde, reacts as follows：
This method process is simple, raw material is easy to get：Catalyst, solvent and raw material can be recycled, and greatly reduce production
Cost, does not pollute to environment, is a kind of production method of green cleaning；But side reaction is more in course of reaction, so as to cause
Yield is relatively low.
(4) fluoride process
2001, Schiemenz of Germany, Berthold etc. were used (R)4P+X—(R=piperidyls, pyrrole radicals；X=has
Machine or inorganic anion) as phase transfer catalyst or co-catalyst, carry out nucleophilic displacement of fluorine or halogen exchange reaction.To chlorobenzene first
Aldehyde in NMP and dimethylbenzene system, is used [(piperidino) with KF4P] Br is when making catalyst preparation 4-Fluorobenzaldehyde, yield
It is 43%；Use instead [(piperidino)4P] Cl when, yield is 54%, but the product postprocessing that this method is obtained compares
It is more complicated.In sum, to there is high cost, high energy consumption, complex process, 4-Fluorobenzaldehyde selectively low many for existing technology
Shortcoming.
Approach described above prepares 4-Fluorobenzaldehyde to p-fluorotoluene oxidation and optimizes and improve from different angles, but
Still suffering from some problems needs to solve：It is still main using the production of batch still batch first in large-scale production；Secondly above-mentioned
It is high for production equipment requirement in method, and catalyst is largely used, while side reaction increases, cause target product to select
Property, low yield and using the continuous flow tubular reactor of ad hoc structure carry out p-fluorotoluene continuous oxidation synthesize to fluorobenzene first
Aldehyde, can many-sided many deficiencies for solving existing process technology.
Tubular reactor is the general designation of the mini-reactor with micro-structural, compared with conventional reactor, tubular reactor
With small volume, specific surface area is big, easily amplifies, and process is continuous, and quick good mixing effect, heat-transfer effect is good, high temperature high voltage resistant etc.
Feature, the continuous flow tubular reactor using ad hoc structure can have to the mixing of reaction mass and mass transfer, diabatic process
Effect control.The contact area that can be effectively increased between reactant by the design to pipeline configuration and size strengthens its mass-and heat-transfer effect
Really, the utilization rate of oxidant is improve, the usage amount of oxidant is reduced and is avoided the use of co-catalyst, while solving
" temperature runaway " phenomenon produced by hot-spot in course of reaction.By the length to tubular reactor and reaction time
Control, can further make raw material and product distribution more optimize it is controllable；Substrate pair can be realized by the flow velocity for adjusting raw material pump
Fluorine p-fluorotoluene carries out reaction and greatly reduces back-mixing into tubular reactor in proportion with oxidant, further reduces secondary anti-
The generation answered, the stability of oxidant and the selectivity of target product are also greatly improved；By setting pressure in tubular reactor
Power safety valve, can in time give off the excessive oxidant in reactor, it is ensured that the safety of reaction is carried out, and level of significance is down to most
It is low.The present invention using ad hoc structure tubular reactor carry out p-fluorotoluene continuous oxidation prepare 4-Fluorobenzaldehyde method it is relative
There is unrivaled advantage in conventional batch production method, and one can be provided for it industrializes quantity-produced improvement
Important approach.
The content of the invention
The present invention is directed to not enough present on, there is provided one kind is in tubular reactor by p-fluorotoluene continuous oxidation system
The method of standby 4-Fluorobenzaldehyde.This method reaction time is short, and production efficiency is high, and mass transfer, heat transfer are optimized significantly, course of reaction
More stablize controllable.Further object of the present invention is, by process of the invention, realizes the continuous oxygen of p-fluorotoluene
That changes stablizes controllable, reduces the generation of accessory substance.Reaction mass is improved by the reinforcing of mass-and heat-transfer process and process optimization
Effective rate of utilization, further reduces the usage amount of oxidant and catalyst and avoids making for co-catalyst during the course of the reaction
With so that effectively save production cost and then the existing industrialized preparing process of improvement.
To achieve the above object, the technical solution adopted by the present invention is：
A kind of method that p-fluorotoluene continuous oxidation is prepared tubular reactor of use special construction 4-Fluorobenzaldehyde, presses
Carried out according to following step：
(1) first at room temperature, by substrate p-fluorotoluene and part carboxylic acid solvent with volume ratio 1:1 is uniformly mixed,
By oxidant and part carboxylic acid solvent with volume ratio 1:1 is well mixed, and then mixes metal complex and pours into p-fluorotoluene-carboxylic
Acid solution, sodium salt is poured into hydrogen peroxide-carboxylic acid solution；By the required reaction time, two kinds of differences of material are calculated
Flow velocity, continuously squeezes into tubular reactor through measuring pump reacted into reaction zone after preheated mixing respectively, reaction temperature
It is controlled by outer loop heat-exchange system；
(2) mol ratio of reaction mass is controlled by adjusting the method for flow velocity and weight calculation, by changing tubular reactor
0.5~15mm of internal diameter of the pipeline, 25~750ml of volume carry out the 60~1800s of residence time of control material hybrid reaction；Reacting
Cheng Hou, product exits into collecting tank from reactor end, and product rectification is separated, and unreacted p-fluorotoluene circular response is produced
Thing 4-Fluorobenzaldehyde rectifying is collected after purification, and wherein the yield of target product 4-Fluorobenzaldehyde is up to 8%~60%.
Wherein described catalyst is cobalt, molybdenum, bromine one or more metal complex catalysts, and it mainly includes：Acetic acid
Cobalt, cobalt oxalate, cobalt carbonate, cobalt naphthenate, sodium molybdate, ammonium molybdate, sodium bromide, ammonium bromide etc., wherein being with oil-soluble catalyst
It is main, can fully be dissolved in p-fluorotoluene, the mol ratio of its consumption and substrate p-fluorotoluene is in (0.005~0.15): 1, wherein
Preferred molar ratio is (0.01~0.08): 1.
Wherein described oxidant is hydrogen peroxide, and its solution concentration is calculated as 5%~50% with mass concentration, and preferred concentration is
10%~35%.Hydrogen peroxide is (1.0~5.0) with the preferred molar ratio of substrate p-fluorotoluene: 1.
Wherein described hydrogen peroxide, in tubular reactor, when hydrogen peroxide passes through reactor volume 50ml, hydrogen peroxide
Start it is rapid decompose, discharge a large amount of molecular oxygens, when it passes through 100ml, almost molecular oxygen form now should be anti-in 100ml
Answer the hydrogen peroxide that isoconcentration is additionally supplemented at volume to enter, reaction is participated in again.
Wherein described carboxylic acid solvent includes：Formic acid, acetic acid, propionic acid, butyric acid, caproic acid, octanoic acid etc..Wherein solvent with to fluorine
The volume ratio of toluene is in (1~5): 1.
Wherein described reaction temperature is 60~110 DEG C, and preferable reaction temperature is 90~105 DEG C, and reaction time is
60s~1800s.
In further technical scheme, the oxidant for having neither part nor lot in reaction is first quenched with dichloromethane sodium after completion of the reaction,
Then extracted by organic solvent, separated obtains target product after purification.
In above-mentioned technical proposal, the described reaction system difference in functionality such as including raw material storage tank, reaction zone, collection of products area
Region.Channel of reactor structure includes：Pipe once-through type channel design, cake formula pulse diameter varied narrow rectangular tube road structure, tiltedly
Square cake formula pulse diameter varied narrow rectangular tube road structure, enhancing mixed type cake formula narrow rectangular tube road structure and Corning's
Heart Cell channel designs.
The present invention has advantages below：
1st, the present invention uses a kind of mode of production of serialization, and the reaction time is short, and reaction condition is gentle, and process safety can
Control, production efficiency is high.
2nd, the present invention is capable of achieving the effective control to course of reaction by the tubular reactor made using different structure, makes
Product rests on the step of aldehyde alcohol one.
3rd, by the way that the utilization rate of its reaction rate and raw material greatly improved to mass transfer in course of reaction, heat transfer intensification,
And the usage amount of oxidant and catalyst is effectively reduced, and the use of co-catalyst is avoided, there is production cost
Effect is saved.
4th, the present invention is easy to operate, applied widely, and production is flexible, can be advised by the expanding production in parallel of reaction unit
Mould.
Brief description of the drawings
Fig. 1 is the process chart that p-fluorotoluene continuous oxidation of the present invention prepares 4-Fluorobenzaldehyde.
Fig. 2 is continuous flow tubular reactor installation drawing used in the present invention：1st, 2- head tanks, 3,4- raw material measuring pumps,
5- preheating zones, 6,7- reaction zones, 8- products are quenched collecting region.
Fig. 3 is tubular reactor channel design schematic diagram used in the present invention, wherein a- once-through types channel design, b- circles
Cake formula pulse diameter varied narrow rectangular tube road, the oblique side cake formula pulse diameter varied narrow rectangular tube roads of c-, d- enhancings mixed type cake formula is flat
Pipeline, the Heart Cell structures microchannel of e-Corning.
Specific embodiment
Cobalt acetate and sodium molybdate are dissolved in the 1# tanks equipped with p-fluorotoluene and acetic acid, the pre- thermal responses of 5# are pumped into by 3#
In device, pre- thermal reactor is heated to 50 DEG C；Sodium bromide is dissolved in the 2# tanks equipped with hydrogen peroxide and acetic acid, 6# is pumped into by 4#
In pre- thermal reactor, pre- thermal reactor is heated to 50 DEG C, then by two strands of preheating materials, is delivered in 7#, 8# reactor, reaction
Device temperature is set in temperature needed for reaction, and product flows out by 8# reactors, using 0 DEG C of cooling, collects products therefrom.
The present invention is described in detail with reference to embodiment, but the following examples are only the present invention preferably implementation method,
Protection scope of the present invention is not limited thereto, technology model of any one skilled in the art in present disclosure
In enclosing, technology according to the present invention scheme and its inventive concept are subject to equivalent substitute or change, should all cover in guarantor of the invention
Within the scope of shield.
Embodiment 1
(1) device：Reference picture 2 determines the connected mode of tubular reactor, and conduit types are：(3a+3b) once-through type passage+
Cake formula pulse diameter varied narrow rectangular tube road, internal diameter of the pipeline is with volume according to flow velocity and reaction time determination, heat transferring medium
It is conduction oil.
(2) 3.03g cobalt acetates and 3.03g sodium molybdates be dissolved in 200ml p-fluorotoluenes respectively and 200ml acetic acid forms mixed
Solution is closed, now n (cobalt acetate)：N (p-fluorotoluene)=0.0075:1,3.03g sodium bromides are dissolved in 15%H2O2Formed
H2O2- acetic acid solution, now n (sodium bromide)：N (p-fluorotoluene)=0.0075:1, p-fluorotoluene-acetic acid solution with and H2O2- second
Acid solution injects the tubular reactor of lasting heat exchange with the flow velocity of 8.33ml/min and 16.67ml/min by constant flow pump respectively
In, now n (H2O2)：N (p-fluorotoluene)=2:1, using Fig. 2 micro passage reactions, 60 DEG C of controlling reaction temperature, residence time
60s.0 DEG C of cooling of outlet material, reaction solution is quenched with dichloromethane.Analyzed by GC, p-fluorotoluene conversion ratio is 40.3%, right
Fluorobenzaldehyde yield is 21.1%.
Embodiment 2
(1) device：Reference picture 2 determines the connected mode of tubular reactor, and conduit types are：(3a+3c) once-through type passage+
Oblique side cake formula pulse diameter varied narrow rectangular tube road, internal diameter of the pipeline determines according to flow velocity and reaction time with volume, exchanges heat and be situated between
Matter is conduction oil.
(2) 6.06g cobalt acetates and 6.06g sodium molybdates be dissolved in 200ml p-fluorotoluenes respectively and 200ml acetic acid forms mixed
Solution is closed, now n (cobalt acetate)：N (p-fluorotoluene)=0.015:1,6.06g sodium bromides are dissolved in 15%H2O2Form H2O2-
Acetic acid solution, now n (sodium bromide)：N (p-fluorotoluene)=0.015:1, p-fluorotoluene-acetic acid solution with and H2O2- acetic acid solution
Injected in the tubular reactor of lasting heat exchange by constant flow pump with the flow velocity of 8.33ml/min and 16.67ml/min respectively, now n
(H2O2)：N (p-fluorotoluene)=2:1, using Fig. 2 micro passage reactions, 95 DEG C of controlling reaction temperature, residence time 600s.Outlet
0 DEG C of cooling of material, reaction solution is quenched with dichloromethane.Analyzed by GC, p-fluorotoluene conversion ratio is 78.0%, 4-Fluorobenzaldehyde
Yield is 45.7%.
Embodiment 3
(1) device：Reference picture 2 determines the connected mode of tubular reactor, and conduit types are：(3a+3d) once-through type passage+
Enhancing mixed type cake formula narrow rectangular tube road, internal diameter of the pipeline is with volume according to flow velocity and reaction time determination, heat transferring medium
It is conduction oil.
(2) 6.06g cobalt acetates and 6.06g sodium molybdates be dissolved in 200ml p-fluorotoluenes respectively and 200ml acetic acid forms mixed
Solution is closed, now n (cobalt acetate)：N (p-fluorotoluene)=0.015:1,6.06g sodium bromides are dissolved in 15%H2O2Form H2O2-
Acetic acid solution, now n (sodium bromide)：N (p-fluorotoluene)=0.015:1, p-fluorotoluene-acetic acid solution with and H2O2- acetic acid solution
Injected in the tubular reactor of lasting heat exchange by constant flow pump with the flow velocity of 8.33ml/min and 16.67ml/min respectively, now n
(H2O2)：N (p-fluorotoluene)=2:1, using Fig. 2 micro passage reactions, 105 DEG C of controlling reaction temperature, residence time 800s.Go out
0 DEG C of cooling of mouth material, reaction solution is quenched with dichloromethane.Analyzed by GC, p-fluorotoluene conversion ratio is 65.8%, to fluorobenzene first
Aldehyde yield is 32.2%.
Embodiment 4
(1) device：Reference picture 2 determines the connected mode of tubular reactor, and conduit types are：(3a+3b) once-through type passage+
Cake formula pulse diameter varied narrow rectangular tube road, internal diameter of the pipeline is with volume according to flow velocity and reaction time determination, heat transferring medium
It is conduction oil.
(2) 6.06g cobalt acetates and 6.06g sodium molybdates be dissolved in 200ml p-fluorotoluenes respectively and 200ml acetic acid forms mixed
Solution is closed, now n (cobalt acetate)：N (p-fluorotoluene)=0.015:1,6.06g sodium bromides are dissolved in 25%H2O2Form H2O2-
Acetic acid solution, now n (sodium bromide)：N (p-fluorotoluene)=0.015:1, p-fluorotoluene-acetic acid solution with and H2O2- acetic acid solution
Injected in the tubular reactor of lasting heat exchange by constant flow pump with the flow velocity of 8.33ml/min and 16.67ml/min respectively, now n
(H2O2)：N (p-fluorotoluene)=2:1, using Fig. 2 micro passage reactions, 105 DEG C of controlling reaction temperature, residence time 900s.Go out
0 DEG C of cooling of mouth material, reaction solution is quenched with dichloromethane.Analyzed by GC, p-fluorotoluene conversion ratio is 77.5%, to fluorobenzene first
Aldehyde yield is 48.1%.
Embodiment 5
(1) device：Reference picture 2 determines the connected mode of tubular reactor, and conduit types are：(3a+3c) once-through type passage+
Oblique side cake formula pulse diameter varied narrow rectangular tube road, internal diameter of the pipeline determines according to flow velocity and reaction time with volume, exchanges heat and be situated between
Matter is conduction oil.
(2) 6.06g cobalt acetates and 6.06g sodium molybdates be dissolved in 200ml p-fluorotoluenes respectively and 200ml acetic acid forms mixed
Solution is closed, now n (cobalt acetate)：N (p-fluorotoluene)=0.015:1,6.06g sodium bromides are dissolved in 25%H2O2Form H2O2-
Acetic acid solution, now n (sodium bromide)：N (p-fluorotoluene)=0.015:1, p-fluorotoluene-acetic acid solution with and H2O2- acetic acid solution
Injected in the tubular reactor of lasting heat exchange by constant flow pump with the flow velocity of 8.33ml/min and 16.67ml/min respectively, now n
(H2O2)：N (p-fluorotoluene)=2:1, using Fig. 2 micro passage reactions, 110 DEG C of controlling reaction temperature, residence time 1200s.Go out
0 DEG C of cooling of mouth material, reaction solution is quenched with dichloromethane.Analyzed by GC, p-fluorotoluene conversion ratio is 30.7%, to fluorobenzene first
Aldehyde yield is 19.1%.
Embodiment 6
(1) device：Reference picture 2 determines the connected mode of tubular reactor, and conduit types are：(3a+3d) once-through type passage+
Enhancing mixed type cake formula narrow rectangular tube road, internal diameter of the pipeline is with volume according to flow velocity and reaction time determination, heat transferring medium
It is conduction oil.
(2) 6.06g cobalt acetates and 6.06g sodium molybdates be dissolved in 200ml p-fluorotoluenes respectively and 200ml acetic acid forms mixed
Solution is closed, now n (cobalt acetate)：N (p-fluorotoluene)=0.015:1,6.06g sodium bromides are dissolved in 25%H2O2Form H2O2-
Acetic acid solution, now n (sodium bromide)：N (p-fluorotoluene)=0.015:1, p-fluorotoluene-acetic acid solution with and H2O2- acetic acid solution
Injected in the tubular reactor of lasting heat exchange by constant flow pump with the flow velocity of 5.56ml/min and 11.11ml/min respectively, now n
(H2O2)：N (p-fluorotoluene)=2:1, using Fig. 2 micro passage reactions, 110 DEG C of controlling reaction temperature, residence time 1500s.Go out
0 DEG C of cooling of mouth material, reaction solution is quenched with dichloromethane.Analyzed by GC, p-fluorotoluene conversion ratio is 34.7%, to fluorobenzene first
Aldehyde yield is 25.8%.
Embodiment 7
(1) device：Reference picture 2 determines the connected mode of tubular reactor, and conduit types are：(3a+3e) once-through type passage+
Corningde Heart Cell structures, internal diameter of the pipeline determines that heat transferring medium is with volume according to flow velocity and reaction time
Conduction oil.
(2) 6.06g cobalt acetates and 6.06g sodium molybdates be dissolved in 200ml p-fluorotoluenes respectively and 200ml acetic acid forms mixed
Solution is closed, now n (cobalt acetate)：N (p-fluorotoluene)=0.015:1,6.06g sodium bromides are dissolved in 25%H2O2Form H2O2-
Acetic acid solution, now n (sodium bromide)：N (p-fluorotoluene)=0.015:1, p-fluorotoluene-acetic acid solution with and H2O2- acetic acid solution
Injected in the tubular reactor of lasting heat exchange by constant flow pump with the flow velocity of 5.56ml/min and 11.11ml/min respectively, now n
(H2O2)：N (p-fluorotoluene)=2:1, using Fig. 2 micro passage reactions, 90 DEG C of controlling reaction temperature, residence time 900s.Outlet
0 DEG C of cooling of material, reaction solution is quenched with dichloromethane.Analyzed by GC, p-fluorotoluene conversion ratio is 10.8%, 4-Fluorobenzaldehyde
Yield is 8.0%.
Embodiment 8
(1) device：Reference picture 2 determines the connected mode of tubular reactor, and conduit types are：(3a+3d) once-through type passage+
Enhancing mixed type cake formula narrow rectangular tube road, internal diameter of the pipeline is with volume according to flow velocity and reaction time determination, heat transferring medium
It is conduction oil.
(2) 6.06g cobalt acetates and 6.06g sodium molybdates be dissolved in 200ml p-fluorotoluenes respectively and 200ml acetic acid forms mixed
Solution is closed, now n (cobalt acetate)：N (p-fluorotoluene)=0.015:1,6.06g sodium bromides are dissolved in 25%H2O2Form H2O2-
Acetic acid solution, now n (sodium bromide)：N (p-fluorotoluene)=0.015:1, p-fluorotoluene-acetic acid solution with and H2O2- acetic acid solution
Injected in the tubular reactor of lasting heat exchange by constant flow pump with the flow velocity of 5.56ml/min and 11.11ml/min respectively, now n
(H2O2)：N (p-fluorotoluene)=2:1, using Fig. 2 micro passage reactions, 100 DEG C of controlling reaction temperature, residence time 900s.Go out
0 DEG C of cooling of mouth material, reaction solution is quenched with dichloromethane.Analyzed by GC, p-fluorotoluene conversion ratio is 37.9%, to fluorobenzene first
Aldehyde yield is 26.7%.
Embodiment 9
(1) device：Reference picture 2 determines the connected mode of tubular reactor, and conduit types are：(3a+3c) once-through type passage+
Oblique side cake formula pulse diameter varied narrow rectangular tube road, internal diameter of the pipeline determines according to flow velocity and reaction time with volume, exchanges heat and be situated between
Matter is conduction oil.
(2) 6.06g cobalt acetates and 6.06g sodium molybdates be dissolved in 200ml p-fluorotoluenes respectively and 200ml acetic acid forms mixed
Solution is closed, now n (cobalt acetate)：N (p-fluorotoluene)=0.015:1,6.06g sodium bromides are dissolved in 25%H2O2Form H2O2-
Acetic acid solution, now n (sodium bromide)：N (p-fluorotoluene)=0.015:1, p-fluorotoluene-acetic acid solution with and H2O2- acetic acid solution
Injected in the tubular reactor of lasting heat exchange by constant flow pump with the flow velocity of 5.56ml/min and 11.11ml/min respectively, now n
(H2O2)：N (p-fluorotoluene)=2:1, using Fig. 2 micro passage reactions, 110 DEG C of controlling reaction temperature, residence time 1800s.Go out
0 DEG C of cooling of mouth material, reaction solution is quenched with dichloromethane.Analyzed by GC, p-fluorotoluene conversion ratio is 85.1%, to fluorobenzene first
Aldehyde yield is 54.3%.
Claims (6)
1. a kind of method that p-fluorotoluene continuous oxidation prepares 4-Fluorobenzaldehyde, it is characterised in that carry out as steps described below：
（1）At room temperature, by substrate p-fluorotoluene and part carboxylic acid solvent with volume ratio 1:1 is uniformly mixed, by oxidant and
Part carboxylic acid solvent is with volume ratio 1:1 is well mixed, and then mixes metal complex and pours into p-fluorotoluene-carboxylic acid solution, will
Sodium salt is poured into hydrogen peroxide-carboxylic acid solution；By the required reaction time, two kinds of different in flow rate, difference of material are calculated
Continuously squeezed into tubular reactor through measuring pump and reacted into reaction zone after preheated mixing, reaction temperature is by outer loop
Heat-exchange system is controlled；
（2）The mol ratio of reaction mass is controlled by the method for adjusting flow velocity and weight calculation, by the pipeline for changing tubular reactor
0.5 ~ 15mm of internal diameter, 25 ~ 750ml of volume carrys out the residence time of control material hybrid reaction；After completion of the reaction, product is from reaction
Device end exits into collecting tank, and product rectification is separated, unreacted p-fluorotoluene circular response, product 4-Fluorobenzaldehyde rectifying
Collect after purification.
2. the method that a kind of p-fluorotoluene continuous oxidation according to claim 1 prepares 4-Fluorobenzaldehyde, it is characterised in that
Described catalyst is cobalt, molybdenum, sodium one or more metal complex catalysts, and it mainly includes：Cobalt acetate, cobalt oxalate, carbon
Sour cobalt, cobalt naphthenate, sodium molybdate, ammonium molybdate, sodium bromide, ammonium bromide etc., wherein based on oil-soluble catalyst, can be to fluorine first
Fully dissolved in benzene, its consumption exists with the mol ratio of substrate p-fluorotoluene（0.005~0.15）: 1, wherein preferred molar ratio is
（0.01~0.08）∶1.
3. the method that a kind of p-fluorotoluene continuous oxidation according to claim 1 prepares 4-Fluorobenzaldehyde, it is characterised in that
Described oxidant is hydrogen peroxide, and its solution concentration is calculated as 5% ~ 50% with mass concentration, and preferred concentration is 15% ~ 30%, hydrogen peroxide
Preferred molar ratio with substrate p-fluorotoluene is（1.0~5.0）∶1.
4. the method that a kind of p-fluorotoluene continuous oxidation according to claim 1 prepares 4-Fluorobenzaldehyde, it is characterised in that
Described carboxylic acid solvent includes：Formic acid, acetic acid, propionic acid, butyric acid, caproic acid, octanoic acid;Wherein solvent exists with the volume ratio of p-fluorotoluene
（1~5）∶1.
5. the method that a kind of p-fluorotoluene continuous oxidation according to claim 1 prepares 4-Fluorobenzaldehyde, it is characterised in that：
Reaction temperature is 60 ~ 110 DEG C, and preferable reaction temperature is 95 ~ 105 DEG C, reaction time 60s ~ 1800s.
6. the method that a kind of p-fluorotoluene continuous oxidation according to claim 1 prepares 4-Fluorobenzaldehyde, it is characterised in that
Total overall reaction process is carried out continuously in the tubular reactor of ad hoc structure, the reaction system include raw material storage tank, reaction zone,
The difference in functionality such as collection of products region;Channel of reactor structure includes：Pipe once-through type channel design, cake formula pulse diameter varied
Narrow rectangular tube road structure, tiltedly side cake formula pulse diameter varied narrow rectangular tube road structure, enhancing mixed type cake formula narrow rectangular tube road knot
Structure, cardioid channel design.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN110655457A (en) * | 2019-09-05 | 2020-01-07 | 门希国 | Novel method for preparing p-fluorobenzaldehyde by catalytic oxidation of hydrogen peroxide |
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|---|---|---|---|---|
| US5473101A (en) * | 1991-06-21 | 1995-12-05 | Solvay Interox Limited | Oxidation of alkylaromatics |
| CN102432448A (en) * | 2011-11-07 | 2012-05-02 | 常州大学 | Method for preparing acetophenone by oxidizing ethylbenzene in continuous flow micro-channel reactor |
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2016
- 2016-11-07 CN CN201610972080.6A patent/CN106748686A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5473101A (en) * | 1991-06-21 | 1995-12-05 | Solvay Interox Limited | Oxidation of alkylaromatics |
| CN102432448A (en) * | 2011-11-07 | 2012-05-02 | 常州大学 | Method for preparing acetophenone by oxidizing ethylbenzene in continuous flow micro-channel reactor |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN110655457A (en) * | 2019-09-05 | 2020-01-07 | 门希国 | Novel method for preparing p-fluorobenzaldehyde by catalytic oxidation of hydrogen peroxide |
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