CN110117216A - A kind of continuous flow preparation method of 2,6- diethyl -4- methyl bromobenzene - Google Patents
A kind of continuous flow preparation method of 2,6- diethyl -4- methyl bromobenzene Download PDFInfo
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- CN110117216A CN110117216A CN201910530204.9A CN201910530204A CN110117216A CN 110117216 A CN110117216 A CN 110117216A CN 201910530204 A CN201910530204 A CN 201910530204A CN 110117216 A CN110117216 A CN 110117216A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/093—Preparation of halogenated hydrocarbons by replacement by halogens
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C245/00—Compounds containing chains of at least two nitrogen atoms with at least one nitrogen-to-nitrogen multiple bond
- C07C245/20—Diazonium compounds
Abstract
The invention discloses one kind 2, the continuous flow preparation method of 6- diethyl -4- methyl bromobenzene, whole preparation process carries out in integrated reactor, diazo reagent is continuously added in integrated reactor feed inlet, acid and 2, 6- diethyl -4- methylaniline, carry out diazo-reaction, gained diazonium salt occurs bromo-reaction with bromide reagent again and is continuously available 2 in integrated reactor discharge port, 6- diethyl -4- methyl bromobenzene crude product, hexahydrotoluene is added and extracts split-phase, organic phase is through washing, saturated sodium carbonate is washed, 2 are obtained after decompression precipitation, 6- diethyl -4- methyl bromobenzene.Production process of the present invention is safe and efficient, does not cause high-risk diazonium salt accumulation, solves the problems, such as that still reaction system viscosity is big, and product yield and purity are higher, and technological operation is simple and efficient.
Description
Technical field
The present invention relates to the preparation methods of pesticide intermediate, are more particularly to the continuous of 2,6- diethyl -4- methyl bromobenzene
Flow preparation method.
Background technique
2,6- diethyl -4- methyl bromobenzene is the key intermediate of herbicide pinoxaden.
CN109134187A, CN106928253A, CN102395546A, CN108864144A knock off between reporting use
2,6- diethyl -4- methylaniline elder generation diazotising, then bromination are prepared 2,6- diethyl -4- methyl by skill (batch process)
The method of bromobenzene.
These methods have the shortcomings that following significant:
(1) security risk is big, and limitation production capacity is promoted.A large amount of diazonium salt is had after diazo-reaction, in reaction kettle to exist,
Cause to explode since diazonium salt easily decomposes, so that there are great security risks in commercial process, so that 2 are limited,
The production capacity of 6- diethyl -4- methyl bromobenzene is promoted.
(2) energy consumption is big, high production cost.To guarantee safety in production, need when preparing diazonium salt at low temperature (- 5 DEG C)
Lower progress, increases energy consumption；Repeatedly heating and cooling operation in production process simultaneously, not only makes cumbersome, but also drops
Low production efficiency.
(3) interval batch operation low efficiency, reaction time are long.The above method needs first to prepare 2,6- diethyl -4- methyl
It, is then carried out bromination reaction by the corresponding diazonium salt of aniline in being slowly dropped to bromide reagent, and technical process needs multiple
Reaction kettle, which cooperates, to be operated, and a batch production generally requires multiple hours, and technological operation is cumbersome, and time-consuming for production, production
Low efficiency.
(4) by-products content is difficult to control.After diazonium salt is prepared, since next step bromination reaction temperature is higher, lead to
It often needs to be slowly dropped to diazonium salt in bromide reagent and carries out bromination reaction, reaction time consumption is long, easily influences the selectivity of reaction
And increase by-products content.
It is, thus, sought for a kind of production safety is efficient, 2,6- diethyl easy to operate, being easy to be mass produced high-purity
Base -4- methyl bromobenzene preparation method.
Summary of the invention
To solve the above problems, the present invention provides the continuous flow preparation method of one kind 2,6- diethyl -4- methyl bromobenzene,
The method carries out in integrated reactor, is continuously added to first material, second in the feed inlet of the integrated reactor
Material, third material and 4 materials, including the diazo-reaction successively carried out and bromination reaction, in the integrated reactor
Discharge port be continuously available 2,6- diethyl -4- methyl bromobenzene；
Contain diazo reagent in the first material, acid is contained in second material, contains 2,6- diethyl in third material
Base -4- methylaniline contains bromide reagent in 4 materials.
The integrated reactor uses modular construction, includes multiple warm areas, each warm area independently includes one
Above reactor module or reactor module group, the reactor module group is by multiple reactor module serial or parallel connection groups
At being connected with each other between each warm area.
Wherein, the preferred continuous current micro-reactor of the integrated reactor.
The continuous current micro-reactor includes at least three sequentially connected independent fluid modules.Each independent fluid modules
Including module inlet and module outlet, the module inlet and module outlet are in fluid communication；Each individually fluid modules include limit
The continuous passage being scheduled in the reaction volume of independent fluid modules, the continuous passage define the reaction volume from reaction volume
The tortuous fluid flow channel that the reaction volume of entrance to reaction volume exports, the reaction volume entrance and module outlet fluid connect
Logical, the reaction volume outlet is in fluid communication with module outlet.
Tortuous fluid flow channel in each individually fluid modules includes multiple having 90 ° to 180 ° of bending angle
Bending.
In continuous current micro-reactor, each individually fluid modules include the reaction volume being limited in independent fluid modules
In continuous passage.The continuous passage is defined from the module inlet of an independent fluid modules to an independent fluid modules
Module outlet tortuous fluid flow channel.As used herein, term " tortuous fluid course " refers to the upper limit in the horizontal direction
It is scheduled between substantially parallel wall and is limited to the fluid channel between substantially parallel surface, the flowing in vertical direction
Channel include it is multiple have be at least 90 °, the bending of preferably about 180 ° of bending angle.In this respect, the multiple bending
Lead to the variation of fluid flow direction, in a preferred embodiment, side of the fluid flow direction relative to independent fluid modules
Edge reverses completely.
The independent fluid modules are made of glass, ceramics or glass-ceramic.
Continuous passage in each individually fluid modules has the continuous passage depth from 0.8~3mm.
Continuous passage in each individually fluid modules has the continuous passage width from 0.7~1.1mm.Each list
Continuous passage in only fluid modules includes multiple continuous mixing chambers, and each continuous mixing chamber includes at least one flow shunt knot
Structure, each continuous mixing chamber have the chamber width greater than continuous passage width.
The chamber width of each continuous mixing chamber is 1~20mm, preferably 3~15mm.
Further, the continuous current micro-reactor includes three to 15 sequentially connected independent fluid modules, and
The microreactor total volume of continuous current micro-reactor is 25mL to 2250mL.
The reaction total time of the method is 0.1~60min.
The total reaction volume of continuous current micro-reactor is that 25.5mL (is not counted in a specific embodiment of the invention
2 module of warm area for temperature control), reaction total time is 7~54s, preferably 7~17s, more preferable 14~15s.
In continuous current micro-reactor, each individually fluid modules can equipped with the thermal control fluid of their own temperature from
Movement controller, it can be advantageous to control reaction temperature, constitute warm area above-mentioned, and independently protect in each independent fluid modules
Hold reaction temperature.Thermal control fluid can be the liquid being arbitrarily easy to get, and with suitable heat exchange functional characteristic, have simultaneously
There are good flow behavior, such as viscosity, to pass through the thermal control volume of independent fluid modules.In a specific implementation of the invention
In mode, thermal control fluid is silicone oil.
The multiple types microchannel continuous flow reactor for meeting above-mentioned condition in the prior art can be used in the method for the present invention
It realizes, such as microchannel continuous flow reactor disclosed in CN102202774A, CN103328440A.
Further, the diazo reagent and acid-mixed are closed, fully reacting or reaction not exclusively, resulting material again with
2,6- diethyl -4- methylaniline carries out diazo-reaction and generates corresponding diazonium salt.
Further, the diazo reagent is selected from nitrite or nitrosylsulfuric acid；The nitrite is selected from Asia
Lithium nitrate, sodium nitrite, potassium nitrite, ammonium nilrite, magnesium nitrite, barium nitrite or calcium nitrite, preferably sodium nitrite.
Further, the feed concentration of the diazo reagent is 10wt%~95wt%；Diazo reagent is nitrous acid
When sodium, feed concentration preferred 20wt%~30wt%, more preferable 25wt%.
Further, the acid is selected from hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid or oxalic acid, preferably hydrobromic acid, hydrobromic acid
The preferred 48wt% of concentration.
Further, the bromide reagent is selected from hydrobromic acid and/or metal bromide.
Further, metal bromide is sodium bromide or potassium bromide.
Further, cuprous salt, molysite or ferrous salt are also contained in 4 materials, preferably sulfuric acid is ferrous.
Further, also contain metal bromide in first material, to increase the concentration of bromide ion in subsequent bromination reaction.
Further, the molar ratio of 2, the 6- diethyl -4- methylaniline and diazo reagent is 1:1~10, preferably
1:1~2, more preferable 1:1.6~1.7.
The molar ratio of 2, the 6- diethyl -4- methylaniline and acid is 1:1~10, preferably 1:1~3, more preferable 1:2.
The molar ratio of bromo element is 1:1~10 in 2, the 6- diethyl -4- methylaniline and the total dosage of bromide reagent, excellent
Select 1:2~6, more preferable 1:4.
Further, the continuous flow synthesis technology carries out in the integrated reactor comprising 4 warm areas, including with
Lower step:
(a) first material and second material are flowed through into 1 hybrid reaction of warm area, third material is in warm area 2 or flows through warm area 2
Pre- controlling temperature；
(b) material for flowing through warm area 1 and material through the pre- controlling temperature of warm area 2 are mixed in warm area 3, flows through warm area 3,
Diazo-reaction is wherein completed, diazonium salt is generated；
(c) diazonium salt of generation is mixed with 4 materials in warm area 4, flows through warm area 4, completes bromo-reaction wherein,
Obtain 2,6- diethyl -4- methyl bromobenzene.
Further, the temperature of the warm area 1 is -15~25 DEG C, preferably 0~15 DEG C, more preferable 5 DEG C；
Further, the temperature of the warm area 2 is -15~25 DEG C, preferably 0~15 DEG C, more preferable 5 DEG C；
Further, the temperature of the warm area 3 is -15~25 DEG C, preferably 0~15 DEG C, more preferable 5 DEG C；
Further, the temperature of the warm area 4 is 0~90 DEG C, preferably 45~80 DEG C, more preferable 80 DEG C.
Further, the residence time of the warm area 1 is 3~18s, preferably 5~8s, more preferable 6s.
Further, the residence time of the warm area 3 is 2~15s, preferably 4~6s, more preferable 4.8s.
Further, the residence time of the warm area 4 is 1~12s, preferably 3~4s, more preferable 3.5s.
Wherein, in the calculating of previous reaction total time, the total time of reaction is the summation of 1,3,4 residence time of warm area,
And it is not counted in the residence time of warm area 2.The reason is that material does not react in warm area 2, only play a part of to control temperature of charge.
In a particular embodiment, in order to simplify temperature control operation, the module of microreactor is also used, but those skilled in the art know
Dawn, a variety of alternatives can be taken to realize identical effect, such as can be with the container of temperature control.
The process of continuous flow preparation method of the present invention is as follows:
Reaction raw materials 2,6- diethyl -4- methylaniline, again is uninterruptedly added in the feed inlet of aforementioned integrated reactor
Diazotizing reagent, acid and bromide reagent.
When carrying out diazo-reaction by continuous stream mode, the prior art such as Org.Process Res.Dev., 2018,
22 (12), pp 1828-1834 usually first mixes arylamine with acid, then reacts with diazo reagent.But by reacting continuous flow
The screening test of hybrid mode finds, for the aniline 2 of specific structure of the present invention, for 6- diethyl -4- methylaniline, with
When acid first mixes, the salt of generation solubility in water phase is lower, causes entire continuous flow reaction efficiency relatively low.
If 6- diethyl -4- methylaniline is first mixed with diazo reagent using 2, easily it is divided into two-phase and is not easy to feed.
Accordingly, it is preferred that mode is first to close diazo reagent and acid-mixed, then carry out with 2,6- diethyl -4- methylaniline
Diazo-reaction generates corresponding diazonium salt.When diazo reagent and acid-mixed are closed, according to the difference of diazo reagent used and acid,
It can react and generate corresponding nitrous acid or nitrosyl.This kind of reaction is usually exothermic, passes through the thermal control stream of reaction unit
Body heat absorption pre-cooling, is conducive to the progress of lower step diazo-reaction.In entire continuous flow reaction process of the invention, relative to rear
Continuous diazo-reaction and bromination reaction, the control to the step hybrid reaction retention time is relatively unessential, and simultaneously should not
Ask certain reaction completely.
The diazo reagent is selected from nitrite or nitrosyl sulfate.The nitrite be selected from lithium nitrite,
Sodium nitrite, potassium nitrite, ammonium nilrite, magnesium nitrite, barium nitrite or calcium nitrite, preferably lower-cost nitrous acid
Sodium.
The feed concentration of the diazo reagent is 10wt%~95wt%, when diazo reagent is sodium nitrite, feed liquid
Concentration preferred 20wt%~30wt%, more preferable 25wt%.When concentration is lower, phenol by-product content increases；When concentration compared with
Gao Shi has part diazonium and salts out, and is unfavorable for entire continuous flow reaction and carries out.
It is outstanding that the feed liquid of the diazo reagent is selected from diazo liquid reagent, diazo reagent slurry liquid, diazo reagent
Turbid, emulsion and solution, preferred aqueous solutions, conducive to the dissolution of subsequent diazonium salt, thus be conducive to entire continuous flow react into
Row.
Since diazotizing subsequent reactions are bromination reactions, preferred hydrobromic acid, to reduce the introducing of New raxa impurity.It is described
The preferred 48wt% of the concentration of hydrobromic acid.Test discovery, reduces the concentration of hydrobromic acid, and the content of phenol by-product increases.
Preferred embodiment is first to mix hydrobromic acid with sodium nitrite, and nitrous acid is prepared in situ.It is anti-to prepare nitrous acid
The temperature answered is -15~25 DEG C.Step reaction is usually exothermic, passes through the thermal control fluid heat absorption control reaction temperature of reaction unit
Degree.Energy consumption is high if temperature is too low；If temperature is excessively high, nitrous acid is easily decomposed, to reduce the yield of entire continuous flow reaction.
Test discovery, at 0~15 DEG C, effect gap is little, therefore it is preferred that 0~15 DEG C.
The temperature of the diazo-reaction is -15~25 DEG C.Due to diazotizing reaction process be it is exothermic, make thermal control stream
The temperature of body slightly below reacts required temperature, to remove extra heat from reaction mixture.The energy consumption if temperature is too low
Height, and easily salt out the diazonium generated and be unfavorable for reacting, especially when the reaction unit used is microreactor, it but will cause
The blocking of reaction module；If temperature is excessively high, diazonium salt is easily decomposed, to reduce the yield of entire continuous flow reaction.Test hair
Existing, at 0~15 DEG C, effect gap is little, therefore it is preferred that 0~15 DEG C.Multiple batches of authentication is found, subsequent to carry out weight when at 5 DEG C
The diazonium salt that nitridation reaction generates is stablized, and reaction stability is higher between batch, and more preferable 5 DEG C.
Preferred embodiment is that the temperature and next step of diazo reagent and acid-mixed conjunction carry out the temperature of diazo-reaction
It is identical, so that the temperature control effect of diazo-reaction is more preferably.
The temperature of the bromination reaction is 0~90 DEG C, preferably 45~80 DEG C, more preferable 80 DEG C.It was reacted due to brominated
Journey be it is exothermic, need higher temperature to cause, actual inside reaction temperature is higher.Temperature is higher to be conducive to mentioning for reaction selectivity
Height, but react excessively high, there is tar generation；The too low then phenol by-product content of temperature increases.
The molar ratio of 2, the 6- diethyl -4- methylaniline and diazo reagent is 1:1~10, preferred 1:1~2, more
It is preferred that 1:1.6~1.7.When using sodium nitrite as diazo reagent, sodium nitrite dosage is anti-between 1.6~1.7eq
Answer effect preferable, if dosage is lower than 1.6eq, raw material conversion is incomplete；If dosage is higher than 1.7eq, impurity and tar can contain
Amount increases, and makes the reduction of final product purity.
The molar ratio of 2, the 6- diethyl -4- methylaniline and acid is 1:1~10, preferably 1:1~3, more preferable 1:2.
When sour dosage is lower than 2eq, raw material conversion is incomplete；When sour dosage is higher than 2eq, by-products content increases, and tar content increases.
In conjunction with integrated reacting above-mentioned as preferred embodiment, the continuous flow synthesis technology is including 4
It is carried out in the integrated reactor of warm area, comprising the following steps:
(a) first material and second material are flowed through into 1 hybrid reaction of warm area, third material is in warm area 2 or flows through warm area 2
Pre- controlling temperature；
(b) material for flowing through warm area 1 and material through the pre- controlling temperature of warm area 2 are mixed in warm area 3, flows through warm area 3,
Diazo-reaction is wherein completed, diazonium salt is generated；
(c) diazonium salt of generation is mixed with 4 materials in warm area 4, flows through warm area 4, completes bromo-reaction wherein,
Obtain 2,6- diethyl -4- methyl bromobenzene.
2, the 6- diethyl -4- methyl bromobenzene that the present invention obtains is crude product, and post-processing can be isolated and purified further.For example,
After bromo-reaction, hexahydrotoluene is added and extracts split-phase, upper organic phase is washed through washing, saturated sodium carbonate respectively, depressurized
Crude product is obtained after precipitation, crude product is evaporated under reduced pressure (10mmHg) through oil pump, collects 80-90 DEG C of fraction and obtains 2, the 6- diethyl of high-purity
Base -4- methyl bromobenzene.
The beneficial effects of the present invention are:
(1) production safety is efficient, does not have diazonium salt accumulation.
(2) easy to operate, production is efficient.
(3) system large viscosity in still reaction is solved the problems, such as.
(4) product yield and purity is high.
Obviously, above content according to the present invention is not being departed from according to the ordinary technical knowledge and customary means of this field
Under the premise of the above-mentioned basic fundamental thought of the present invention, the modification, replacement or change of other diversified forms can also be made.
The specific embodiment of form by the following examples remakes further specifically above content of the invention
It is bright.But the range that this should not be interpreted as to the above-mentioned theme of the present invention is only limitted to example below.It is all to be based on above content of the present invention
The technology realized all belongs to the scope of the present invention.
Detailed description of the invention
Fig. 1 is the reaction process schematic diagram of the embodiment of the present invention 1.
Fig. 2 is the reaction process schematic diagram of the embodiment of the present invention 2.
Specific embodiment
In following specific embodiments, purity is HPLC purity, and the residence time is in terms of module.The reaction unit used for
Healthy and free from worry microchannel G1 glass reactor.
Embodiment 1
As shown in Figure 1, taking 48wt%HBr aqueous solution and the NaNO of 25wt%2Aqueous solution is respectively with 37g/min and 52g/
The flow of min is passed through pre-cooling module and carries out mixing pre-cooling, residence time 7.3s at 5 DEG C.Separately take 2,6- diethyl -4- methylbenzene
Amine is passed through another pre-cooling module with 18g/min flow and is pre-chilled at 5 DEG C, residence time 26.6s.The pressure of microreactor is
0.6Mpa。
Material after pre-cooled, which is passed through in next module mix and react at 5 DEG C, generates intermediate diazonium salt,
Residence time 5.7s.
The intermediate diazonium salt of generation continues to be passed through in next bromo module, while according to 0.5eq FeSO4.7H2O:
The proportional arrangement solution of 2eq48%HBr:1eq NaBr is simultaneously passed into bromo-reaction module with the speed of 64g/min, at 80 DEG C
Lower completion bromo-reaction, residence time 4s.
The overall reaction residence time of entire continuous flow reaction is 17s.
After bromo-reaction, hexahydrotoluene is added and extracts split-phase, upper organic phase is respectively through washing, saturated sodium carbonate
Wash, depressurize precipitation after obtain 2,6- diethyl -4- methyl bromobenzene, yield 94%, purity 90%.
Embodiment 2
As shown in Fig. 2, taking 48wt%HBr aqueous solution and the NaNO of 48wt%2/ NaBr (1.7eq:2eq) aqueous solution difference
Pre-cooling module, which is passed through, with the flow of 41.3g/min and 82.6g/min carries out mixing pre-cooling, residence time 6.0s at 5 DEG C.Separately take
2,6- diethyl -4- methylanilines are passed through another pre-cooling module with 20g/min flow and are pre-chilled at 5 DEG C, residence time 24s.It is micro-
The pressure of reactor is 0.9Mpa.
Material after pre-cooled, which is passed through in next module mix and react at 5 DEG C, generates intermediate diazonium salt,
Residence time is 4.8s.
The intermediate diazonium salt of generation continues to be passed through in next bromo module, while according to 0.5eq FeSO4.7H2O:
The proportional arrangement bromo solution of 2eq48%HBr is simultaneously passed into bromo-reaction module with the speed of 58.2g/min, at 80 DEG C
Complete bromo-reaction, residence time 3.5s.
The overall reaction residence time of entire continuous flow reaction is 14.3s.
After bromo-reaction, hexahydrotoluene is added and extracts split-phase, upper organic phase is respectively through washing, saturated sodium carbonate
Wash, depressurize precipitation after obtain 2,6- diethyl -4- methyl bromobenzene, yield 92%, purity 96%.
Comparative example still reaction
First 2,6- diethyl -4- methylaniline (1eq) is added dropwise in 48wt% hydrobromic acid (3eq) aqueous solution in 70-80
Sufficiently reaction is at salt at DEG C, and system viscosity is gradually increased in salification process, and rear system solid content is added dropwise and reaches 40%, flowing
Property is poor.Then system being reduced to -10~-15 DEG C by 80 DEG C or so, a large amount of aniline salt out in system at this time, and viscosity is into one
Step becomes larger in starchiness, then sodium nitrite in aqueous solution (1.1eq) the progress diazo-reaction of 25wt% is slowly added dropwise.Separately take 1eq
48wt% hydrobromic acid, 0.5eq ferrous sulfate heptahydrate, 3eq sodium bromide, mixing are heated to 80 DEG C and prepare brominated reagent, will be upper
Counter be added dropwise in brominated reagent of diazotising of one step preparation completes bromo-reaction, and process is added dropwise and is kept for 70-80 DEG C of temperature, drips
After be stirred to react 30min.Later, hexahydrotoluene is added and extracts split-phase, upper organic phase vacuum distillation recovered solvent, product is received
Rate 85%, purity 92%.
Claims (16)
1. one kind 2, the continuous flow preparation method of 6- diethyl -4- methyl bromobenzene, it is characterised in that: the method is integrated anti-
It answers in device and carries out, be continuously added to first material, second material, third material and the 4th in the feed inlet of the integrated reactor
Material is continuously available 2 in the discharge port of the integrated reactor including the diazo-reaction successively carried out and bromination reaction,
6- diethyl -4- methyl bromobenzene；
Contain diazo reagent in the first material, acid is contained in second material, contains 2,6- diethyl -4- in third material
Methylaniline contains bromide reagent in 4 materials.
2. continuous flow preparation method according to claim 1, it is characterised in that: the integrated reactor uses module
Change structure, include multiple warm areas, each warm area independently includes more than one reactor module or reactor module group, described
Reactor module group be connected in series or in parallel by multiple reactor modules, be connected with each other between each warm area；Preferred integration
Reactor is continuous current micro-reactor.
3. continuous flow preparation method according to claim 2, it is characterised in that: the continuous current micro-reactor includes at least
Three sequentially connected independent fluid modules；Preferably, the continuous current micro-reactor includes three to 15 sequentially connected
Independent fluid modules, and the microreactor total volume of continuous current micro-reactor is 25mL to 2250mL.
4. continuous flow preparation method according to claim 3, it is characterised in that: the total time of the reaction be 0.1~
60min, preferably 7~54s, more preferable 7~18s, most preferably 14~15s.
5. continuous flow preparation method according to claim 3, it is characterised in that: the song in each individually fluid modules
Deflector body runner includes the bending of multiple bending angle with 90 ° to 180 °.
6. continuous flow preparation method according to claim 3, it is characterised in that: the company in each individually fluid modules
Continuous channel has the continuous passage depth from 0.8~3mm；Continuous passage in each solely fluid modules has from 0.7~
The continuous passage width of 1.1mm.
7. continuous flow preparation method according to claim 3, it is characterised in that: continuous logical in each individually fluid modules
Road includes multiple continuous mixing chambers, and each continuous mixing chamber includes at least one flow shunt structure, each continuous mixing chamber tool
There is the chamber width greater than continuous passage width；Preferably, the chamber width of each continuous mixing chamber is 1~20mm, more preferable 3
~15mm.
8. continuous flow preparation method according to claim 1-7, it is characterised in that: first make the diazo reagent
It is closed with acid-mixed, not exclusively, resulting material carries out diazo-reaction with 2,6- diethyl -4- methylaniline again for fully reacting or reaction
Generate corresponding diazonium salt.
9. continuous flow preparation method according to claim 1-8, it is characterised in that: the diazo reagent is selected from
Nitrite or nitrosylsulfuric acid；The nitrite is selected from lithium nitrite, sodium nitrite, potassium nitrite, ammonium nilrite, Asia
Magnesium nitrate, barium nitrite or calcium nitrite, preferably sodium nitrite.
10. -9 described in any item continuous flow preparation methods according to claim 1, it is characterised in that: the diazo reagent
Feed concentration is 10wt%~95wt%；When the diazo reagent is sodium nitrite, the preferred 20wt% of feed concentration~
30wt%, more preferable 25wt%.
11. -10 described in any item continuous flow preparation methods according to claim 1, it is characterised in that: it is described acid selected from hydrochloric acid,
Hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid or oxalic acid, preferably hydrobromic acid, the preferred 48wt% of the concentration of hydrobromic acid.
12. -11 described in any item continuous flow preparation methods according to claim 1, it is characterised in that: the bromide reagent is selected from
Hydrobromic acid and/or metal bromide, preferred metal bromide are sodium bromide or potassium bromide；
Also contain cuprous salt, molysite or ferrous salt in the 4 materials, preferably sulfuric acid is ferrous；
It is preferred that also containing metal bromide in first material.
13. -12 described in any item continuous flow preparation methods according to claim 1, it is characterised in that: 2, the 6- diethyl -
The molar ratio of 4- methylaniline and diazo reagent is 1:1~10, preferably 1:1~2, more preferable 1:1.6~1.7；
The molar ratio of 2, the 6- diethyl -4- methylaniline and acid is 1:1~10, preferably 1:1~3, more preferable 1:2；
The molar ratio of bromo element is 1:1~10 in 2, the 6- diethyl -4- methylaniline and the total dosage of bromide reagent, preferably 1:
2~6, more preferable 1:4.
14. according to the described in any item continuous flow preparation methods of claim 1-13, it is characterised in that: the continuous flow synthesizes work
Skill carries out in the integrated reactor comprising 4 warm areas, comprising the following steps:
(a) first material and second material are flowed through into 1 hybrid reaction of warm area, third material is in warm area 2 or flows through 2 pre-control of warm area
Temperature；
(b) material for flowing through warm area 1 and material through the pre- controlling temperature of warm area 2 are mixed in warm area 3, flows through warm area 3, wherein
Diazo-reaction is completed, diazonium salt is generated；
(c) diazonium salt of generation is mixed with 4 materials in warm area 4, flows through warm area 4, complete bromo-reaction wherein, obtains
2,6- diethyl -4- methyl bromobenzene.
15. continuous flow preparation method according to claim 14, it is characterised in that: the temperature of the warm area 1 is -15~25
DEG C, preferably 0~15 DEG C, more preferable 5 DEG C；
The temperature of the warm area 2 is -15~25 DEG C, preferably 0~15 DEG C, more preferable 5 DEG C；
The temperature of the warm area 3 is -15~25 DEG C, preferably 0~15 DEG C, more preferable 5 DEG C；
The temperature of the warm area 4 is 0~90 DEG C, preferably 45~80 DEG C, more preferable 80 DEG C.
16. continuous flow preparation method according to claim 15, it is characterised in that: the residence time of the warm area 1 be 3~
18s, preferably 5~8s, more preferable 6s；
The residence time of the warm area 3 is 2~15s, preferably 4~6s, more preferable 4.8s；
The residence time of the warm area 4 is 1~12s, preferably 3~4s, more preferable 3.5s.
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| CN201910530204.9A CN110117216B (en) | 2019-06-19 | 2019-06-19 | Continuous flow preparation method of 2, 6-diethyl-4-methyl bromobenzene |
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| CN114181112A (en) * | 2021-12-13 | 2022-03-15 | 浙江中山化工集团股份有限公司 | Preparation method of 2, 6-diethyl-4-methylphenyl malononitrile |
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| CN113754512B (en) * | 2021-08-31 | 2024-05-17 | 浙江巍华新材料股份有限公司 | Preparation method of o-bromobenzotrifluoride |
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| CN114907181A (en) * | 2021-02-09 | 2022-08-16 | 北京颖泰嘉和生物科技股份有限公司 | Device for sandmeyer reaction and method for continuously preparing 2, 6-diethyl-4-methyl bromobenzene |
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| CN113754512B (en) * | 2021-08-31 | 2024-05-17 | 浙江巍华新材料股份有限公司 | Preparation method of o-bromobenzotrifluoride |
| CN114181112A (en) * | 2021-12-13 | 2022-03-15 | 浙江中山化工集团股份有限公司 | Preparation method of 2, 6-diethyl-4-methylphenyl malononitrile |
| CN114181112B (en) * | 2021-12-13 | 2024-01-09 | 浙江中山化工集团股份有限公司 | Preparation method of 2, 6-diethyl-4-methylphenyl malononitrile |
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