CN106905104A - A Kind of Synthetic Method of The Fluoride Trifluoro Toluene of 2 Bromine 5 - Google Patents PDF

26/12/2020 CN106905104A - A kind of synthetic method of the fluoride trifluoro toluene of 2 bromine 5 - Google Patents
Patents
A kind of synthetic method of the uoride tri uoro toluene of 2 bromine 5
Abstract
CN106905104A
A kind of synthetic method of the uoride tri uoro toluene of 2 bromine 5, belongs to the eld of
China
chemical synthesis.With o-tri uoromethyl aniline as initiation material, speci c steps include： Unexaminded application
（1）Sandmeyer bromination reaction；（2）Nitration reaction；（3）Catalytic hydrogenating
reduction reacts；（4）Diazotising uoro-reaction.A kind of synthetic method of above-mentioned Download PDF Find Prior Art Similar
uoride tri uoro toluene of 2 bromine 5, with o-tri uoromethyl aniline as raw material, through
sandmeyer reaction bromo, nitri cation, hydrogenating reduction, most the uoride tri uoro toluene Other languages: Chinese
of 2 bromine 5 is synthesized through diazotising uoro afterwards, purity reaches more than
Inventor: 陈静华, 吴江伟, 卜鲁周, 李俊奇, 常绚超, 张泉泉, 赵红英
99.0%, dopant species are few, product quality and performances stabilization.
Classi cations Worldwide applications
2017 CN
C07C17/093 Preparation of halogenated hydrocarbons by replacement by halogens
View 2 more classi cations Application CN201710002434.9A events
2017-01-03 Application led by 浙江巍华化工有限公司
2017-01-03 Priority to CN201710002434.9A
2017-06-30 Publication of CN106905104A
2019-12-24 Application granted
2019-12-24 Publication of CN106905104B
Info: Patent citations (3), Non-patent citations (1), Cited by (1),

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Claims (10) Hide Dependent
1. a kind of synthetic method of 2-bromo-5- uorobenzotri uoride, it is characterised in that：With o-tri uoromethyl aniline as initiation material, Speci c steps
include：
（1）Sandmeyer bromination reaction
O-tri uoromethyl aniline is added equipped with, into salt, being then cooled to 0 DEG C and start in the hydrobromic acid ask that mass concentration is 40% The
NaNO that mass concentration is 30% is added dropwise2The aqueous solution, control temperature is not higher than 5 DEG C, drips rear application
Unexaminded insulated and stirred 25-
35min, makes It is standby to obtain faint yellow diazol clari ed solution；Cuprous bromide, 40% hydrobromic acid of catalytic amount are added in another four-hole
bottle, under normal temperature acutely Stirring, the diazo liquid of preparation is poured into four mouthfuls of reaction bulbs, and reaction has a large amount of
gases to produce, and diazo liquid continues to stir after adding 15-25min, split-phase, lower oor's organic phase simple distillation after alkali cleaning, washing
obtains yellow liquid neighbour's 5 bromine benzotri uoride；
（2）Nitration reaction
To 98% fuming nitric aicd is slowly added in 98% concentrated sulfuric acid under normal temperature, stirring, mixed acid nitration is made into, 50-60 DEG C of control
is to nitre Change the adjacent 5 bromine benzotri uoride of dropwise addition in nitration mixture, nish rear insulated and stirred, GC detections are reaction end
without raw material；Split-phase, upper strata Organic phase simple distillation after alkali cleaning, washing obtains the glassy yellow liquid nitro compounds bromo-
5- nitro-tri uoromethyl toluenes of 2-；
（3）Catalytic hydrogenating reduction reacts
To sequentially adding the bromo- 5- nitro-tri uoromethyl toluenes of solvent methanol, nitro compounds 2-, catalyst Raney in high-pressure hydrogenation reactor Ni,
dehalogenation inhibitors, are reacted after being replaced with hydrogen at a temperature of 0.8-1.0Mpa, 80-90 DEG C, until reaction is no longer inhaled Untill
hydrogen；Catalyst is ltered after reaction solution cooling, weak yellow liquid amino substance is obtained after methanol removal, removing moisture, simple
distillation The bromo- 3- 5-tri uoromethylanilines of 4-, catalyst Raney Ni and solvent methanol recovery；
（4）Diazotising uoro-reaction
Stainless steel cauldron is cooled to -8 DEG C~-12 DEG C, successively to addition anhydrous hydro uoric acid, anhydrous potassium uoride, amino in kettle , then
under agitation be added in reaction system natrium nitrosum in batches, and make reaction system temperature by the bromo- 3- 5-tri uoromethylanilines of thing 4-
Degree is no more than 5 DEG C, and stirring 25-35 min are continued after adding makes diazo-reaction complete；It is warming up to 58-62 DEG C and maintains this
temperature Degree, uorination diazol starts slowly to decompose and release gas, and tail gas is by alkali liquor absorption after a cooling buffer unit；Reaction is no
longer Reacted after releasing gas and terminated, will cooled down after unnecessary hydro uoric acid is reclaimed in kettle, the hydro uoric acid of recovery is used
through dewater treatment rear enclosure；To 10%KOH solution is added to be neutralized to neutrality in kettle, steam distillation obtains colourless liquid 2-bromo-5-
uorobenzotri uoride crude product, through ller Rectifying column recti cation under vacuum, colourless transparent liquid i.e. 2-bromo-5- uorobenzotri uoride is
obtained in 110 DEG C of -120 DEG C of cuts are collected under 40mmHg Product.
2. a kind of synthetic method of 2-bromo-5- uorobenzotri uoride as claimed in claim 1, it is characterised in that step（1）In：Drop Plus NaNO2The complete rear
insulated and stirred 28-30min of the aqueous solution, diazo liquid continues to stir 18-20min after adding.
3. a kind of synthetic method of 2-bromo-5- uorobenzotri uoride as claimed in claim 1, it is characterised in that step（1）In： Hydrogen bromide in the preparation of
diazol, is 3.0-3.5 with the mol ratio of o-tri uoromethyl aniline：1, preferably 3.2-3.4：1；In diazonium The mol ratio that salt decomposes hydrogen bromide and o-
tri uoromethyl aniline in bromo is 0.2-0.3：1, preferably 0.0.24-0.28：1.
4. a kind of synthetic method of 2-bromo-5- uorobenzotri uoride as claimed in claim 1, it is characterised in that step（1）In：It is sub- Sodium
Unexaminded nitrate is 1.05-1.1 with
application
the mol ratio of o-tri uoromethyl aniline：1, preferably 1.08-1.0：1.
5. a kind of synthetic method of 2-bromo-5- uorobenzotri uoride as claimed in claim 1, it is characterised in that step（1）In：Urge Agent cuprous bromide is 0.15-
0.50 with the mol ratio of o-tri uoromethyl aniline：1, preferably 0.2-0.4：1.
6. a kind of synthetic method of 2-bromo-5- uorobenzotri uoride as claimed in claim 1, it is characterised in that step（2）In： 98% concentrated sulfuric acid：98%
fuming nitric aicd：The mol ratio of adjacent 5 bromine benzotri uoride is 1.3-1.6：1.1：1.
7. a kind of synthetic method of 2-bromo-5- uorobenzotri uoride as claimed in claim 1, it is characterised in that step（3）In：Institute The dehalogenation inhibitors
stated are the one kind in morpholine, piperazine, ortho-nitraniline, triphenyl phosphate, triphenyl phosphorous acid, and dehalogenation suppresses Agent
consumption is the 0.3%-0.4%, preferably 0.34%-0.38% of the bromo- 5- nitro-tri uoromethyl toluenes quality of nitro compounds 2-.
8. a kind of synthetic method of 2-bromo-5- uorobenzotri uoride as claimed in claim 1, it is characterised in that step（4）In：Nothing The consumption of water
hydro uoric acid is 19-25 with the bromo- 3- 5-tri uoromethylanilines mol ratios of amino substance 4-：1, preferably 20-24：1, more preferably 21-23：1.
9. a kind of synthetic method of 2-bromo-5- uorobenzotri uoride as claimed in claim 1, it is characterised in that step（4）In：Nothing The consumption of water
potassium uoride is 2.0%-5.0%, the preferably 2.5%-4.5% of the bromo- 3- 5-tri uoromethylanilines quality of amino substance 4-, more preferably 3%-4%。
10. a kind of synthetic method of 2-bromo-5- uorobenzotri uoride as claimed in claim 1, it is characterised in that step（4）In： The consumption of natrium nitrosum
is 1.05-1.1 with the mol ratio of amino substance：1, preferably 1.08-1.0：1.
Description
A kind of synthetic method of 2-bromo-5- uorobenzotri uoride
Technical eld
The invention belongs to the eld of chemical synthesis, specially a kind of synthetic method of 2-bromo-5- uorobenzotri uoride.
Background technology
2-bromo-5- uorobenzotri uoride is weak yellow liquid, is important medicine, agricultural chemicals and New Liquid Crystal material intermediate, As it is the important
intermediate of synthesizing antineoplastic medicament Bicalutamide, Bicalutamide is a kind of non-steroid sterol of antiandrogen, With good tolerance, rear non-
evident effect is taken.As 2-bromo-5- uorobenzotri uoride purposes constantly expands, market needs The amount of asking also expands day by day.2-bromo-5-
uorobenzotri uoride synthetic method domestic and foreign literature reports less, patent publication No. CN 102951996 to report with a uoride tri uoro toluene be
raw material, through nitri cation, catalytic hydrogenating reduction, nally by sandmeyer reaction Bromo has synthesized target compound, total recovery
76.1%.Patent publication No. CN 104447183 is reported with 3-Aminotri uorotoluene It is raw material, rst with amido protecting agent by amido protecting, then
phenyl ring bromo is carried out with bromide reagent, deaminizating protection group, nally Through schiemann reaction uoro synthesising target compound, total
recovery 82%, initiation material 3-Aminotri uorotoluene price used by the method It is higher, and amino protecting agent has been used, phenyl ring bromo uses a
large amount of solvents and oxidant, this not only adds production cost, also Produce a large amount of three wastes.It is raw material that patent publication No. CN
104610015 is reported with a uoride tri uoro toluene, with sulfuric acid solution as molten Agent, bromic acid or bromate obtain target compound for the direct bromo
Unexaminded application
of bromide reagent, and highest yield 93.9%, starting used by the method is former Fluoride tri uoro toluene price is high between material, and a large amount of spent
acid are equally produced in phenyl ring bromo-reaction, and not disposable.
The content of the invention
For the above-mentioned problems in the prior art, a kind of bromo- 5- uorine three of 2- is provided it is an object of the invention to design The technical scheme of
the synthetic method of toluene uoride, its with o-tri uoromethyl aniline as raw material, through sandmeyer reaction bromo, nitri cation, Hydrogenating reduction,
most 2-bromo-5- uorobenzotri uoride is synthesized through diazotising uoro afterwards, purity reaches more than 99.0%, dopant species It is few, product quality
and performances stabilization.
Reaction mechanism of the present invention is as follows：
A kind of synthetic method of described 2-bromo-5- uorobenzotri uoride, it is characterised in that：With o-tri uoromethyl aniline as rise Beginning raw material,
speci c steps include：
（1）Sandmeyer bromination reaction
O-tri uoromethyl aniline is added equipped with, into salt, being then cooled to 0 DEG C and start in the hydrobromic acid ask that mass concentration is 40% The
NaNO that mass concentration is 30% is added dropwise2The aqueous solution, control temperature is not higher than 5 DEG C, drips rear insulated and stirred 25-
35min, makes It is standby to obtain faint yellow diazol clari ed solution；Cuprous bromide, 40% hydrobromic acid of catalytic amount are added in another four-hole
bottle, under normal temperature acutely Stirring, the diazo liquid of preparation is poured into four mouthfuls of reaction bulbs, and reaction has a large amount of
gases to produce, and diazo liquid continues to stir after adding 15-25min, split-phase, lower oor's organic phase simple distillation after alkali cleaning, washing
obtains yellow liquid neighbour's 5 bromine benzotri uoride；
（2）Nitration reaction
To 98% fuming nitric aicd is slowly added in 98% concentrated sulfuric acid under normal temperature, stirring, mixed acid nitration is made into, 50-60 DEG C of control
is to nitre Change the adjacent 5 bromine benzotri uoride of dropwise addition in nitration mixture, nish rear insulated and stirred, GC detections are reaction end
without raw material；Split-phase, upper strata Organic phase simple distillation after alkali cleaning, washing obtains the glassy yellow liquid nitro compounds bromo-
5- nitro-tri uoromethyl toluenes of 2-；
To sequentially adding the bromo- 5- nitro-tri uoromethyl toluenes of solvent methanol, nitro compounds 2-, catalyst Raney in high-pressure hydrogenation reactor Ni,
dehalogenation inhibitors, are reacted after being replaced with hydrogen at a temperature of 0.8-1.0Mpa, 80-90 DEG C, until reaction is no longer inhaled Untill
hydrogen；Catalyst is ltered after reaction solution cooling, weak yellow liquid amino substance is obtained after methanol removal, removing moisture, simple
distillation The bromo- 3- 5-tri uoromethylanilines of 4-, catalyst Raney Ni and solvent methanol recovery； Unexaminded application
Stainless steel cauldron is cooled to -8 DEG C~-12 DEG C, successively to addition anhydrous hydro uoric acid, anhydrous potassium uoride, amino in kettle , then
under agitation be added in reaction system natrium nitrosum in batches, and make reaction system temperature by the bromo- 3- 5-tri uoromethylanilines of thing 4-
Degree is no more than 5 DEG C, and stirring 25-35 min are continued after adding makes diazo-reaction complete；It is warming up to 58-62 DEG C and maintains this
temperature Degree, uorination diazol starts slowly to decompose and release gas, and tail gas is by alkali liquor absorption after a cooling buffer unit；Reaction is no
longer Reacted after releasing gas and terminated, will cooled down after unnecessary hydro uoric acid is reclaimed in kettle, the hydro uoric acid of recovery is used
through dewater treatment rear enclosure；To 10%KOH solution is added to be neutralized to neutrality in kettle, steam distillation obtains colourless liquid 2-bromo-5-
uorobenzotri uoride crude product, through ller Rectifying column recti cation under vacuum, colourless transparent liquid i.e. 2-bromo-5- uorobenzotri uoride is
obtained in 110 DEG C of -120 DEG C of cuts are collected under 40mmHg Product.
A kind of synthetic method of described 2-bromo-5- uorobenzotri uoride, it is characterised in that step（1）In：NaNO is added dropwise2Water The complete rear
insulated and stirred 28-30min of solution, diazo liquid continues to stir 18-20min after adding.
A kind of synthetic method of described 2-bromo-5- uorobenzotri uoride, it is characterised in that step（1）In：In diazol Hydrogen bromide in preparation, is 3.0-3.5
with the mol ratio of o-tri uoromethyl aniline：1, preferably 3.2-3.4：1；Bromine is decomposed in diazol Hydrogen bromide and the mol ratio of o-tri uoromethyl
aniline are 0.2-0.3 in generation：1, preferably 0.0.24-0.28：1.In diazo-reaction The general action of inorganic acid has dissolving arylamine, produces HNO2With
maintenance reaction medium highly acid.When mol ratio is less than 3：When 1, acid Amount is not enough, and the diazol of generation is easily and unreacted
arylamine occurs to generate substantial amounts of diazoamino chemical combination from coupling reaction Thing.And work as mol ratio more than 3.5：When 1,
excessive acid causes to waste.When mol ratio is 3.0-3.5：When 1, its selecting response Property and yield are very nearly the same.
A kind of synthetic method of described 2-bromo-5- uorobenzotri uoride, it is characterised in that step（1）In：Natrium nitrosum with The mol ratio of o-
tri uoromethyl aniline is 1.05-1.1：1, preferably 1.08-1.0：1.Work as NaNO2Consumption less than 1.0 equivalent when, Easily occur to produce diazoamino
compound from coupling reaction.But the NaNO of too excessive2Because can aoxidize and nitrosylation etc. draw Send out side reaction a series of, cause yield to
reduce.The rate of addition of other sodium nitrite solution is also critically important, NaNO2Charging speed Degree, depending on the speed of diazo-reaction speed,
main purpose is to ensure not lack nitrous from start to nish in whole course of reaction Sour sodium.Fed intake slow, having little time the arylamine of effect can
produce the yellow mercury oxide of diazoamino thing with diazonium salt action；If fed intake It is too fast, locality natrium nitrosum excess can be caused, heat
release is too fast, it is di cult to control, while nitrous acid throughput rate exceedes diazotising To its wear rate, then this part nitrous acid is set to decompose loss,
and produce poisonous, irritative gas NOx.Therefore, it is necessary to Asia Sodium nitrate feed rate is controlled.
A kind of synthetic method of described 2-bromo-5- uorobenzotri uoride, it is characterised in that step（1）In：Catalyst bromination The cuprous mol ratio with o-
tri uoromethyl aniline is 0.15-0.50：1, preferably 0.2-0.4：1.Cuprous bromide is the sandmeyer The catalyst of bromo-reaction.
A kind of synthetic method of described 2-bromo-5- uorobenzotri uoride, it is characterised in that step（2）In：98% concentrated sulfuric acid： 98% fuming nitric
aicd：The mol ratio of adjacent 5 bromine benzotri uoride is 1.3-1.6：1.1：1.
A kind of synthetic method of described 2-bromo-5- uorobenzotri uoride, it is characterised in that step（3）In：Described dehalogenation Inhibitor is the one kind in
morpholine, piperazine, ortho-nitraniline, triphenyl phosphate, triphenyl phosphorous acid, and dehalogenation inhibitors consumption is The 0.3%-0.4%, preferably
0.34%-0.38% of the bromo- 5- nitro-tri uoromethyl toluenes quality of nitro compounds 2-.Dehalogenation inhibitors Main Function is Prevent from being prevented
when nitro-catalytic hydrogenation is reduced the halogen bromine on phenyl ring from being sloughed by catalysis reduction.
A kind of synthetic method of described 2-bromo-5- uorobenzotri uoride, it is characterised in that step（4）In：Anhydrous hydro uoric acid Consumption and the
bromo- 3- 5-tri uoromethylanilines mol ratios of amino substance 4- be 19-25：1, preferably 20-24：1, more preferably 21-23：1.Nothing Water hydro uoric acid is the
inorganic acid in the diazo-reaction, its same step of effect（1）The effect of middle hydrobromic acid, because the reaction is also with nothing Water hydro uoric
acid is solvent, so large usage quantity, when mol ratio is less than 19：When 1, acid amount is not enough, and yield is low.And work as mol ratio and be more than
25：When 1, excessive acid can cause the cost recovery to increase.
A kind of synthetic method of described 2-bromo-5- uorobenzotri uoride, it is characterised in that step（4）In：Anhydrous potassium uoride Consumption for the
bromo- 3- 5-tri uoromethylanilines quality of amino substance 4- 2.0%-5.0%, more preferably preferably 2.5%-4.5%, 3%-4%.Fluorine Change the catalyst that potassium
is the uoro-reaction, for improving uoro-reaction yield.
A kind of synthetic method of described 2-bromo-5- uorobenzotri uoride, it is characterised in that step（4）In：Natrium nitrosum Consumption is 1.05-1.1 with the
mol ratio of amino substance：1, preferably 1.08-1.0：1.The same step of effect of natrium nitrosum（1）Middle nitrous The effect of sour sodium.
The synthetic method of above-mentioned a kind of 2-bromo-5- uorobenzotri uoride, with o-tri uoromethyl aniline as raw material, through sandmeyer Reaction
bromo, nitri cation, hydrogenating reduction, has most synthesized 2-bromo-5- uorobenzotri uoride through diazotising uoro afterwards, and purity reaches 99.0%
More than, dopant species are few, product quality and performances stabilization；The raw materials used o-tri uoromethyl aniline of the method is cheap, and three
Can all there be a certain proportion of o-tri uoromethyl aniline byproduct in methyl uoride Aniline Production enterprise when 3-Aminotri uorotoluene is produced
Generation, up to 99.5%, because o-tri uoromethyl aniline range of application is small, market demand is small, so cheap for purity.The method The reaction
temperature being related to is moderate, and all of reaction has all industrially been applied and safely controllable.
Speci c embodiment
Embodiment 1
A kind of synthetic method of 2-bromo-5- uorobenzotri uoride, with o-tri uoromethyl aniline as initiation material, speci c steps include：
（1）, sandmeyer bromo-reaction
To 900 mL hydrobromic acids under normal gentle agitation（40%）In be slowly added to 308 g（1.9mol）O-tri uoromethyl aniline, plus It is cooled with an ice bath
after complete to 0 DEG C.By 135 g（1.95mol）Natrium nitrosum is dissolved in 290 mL water, and reaction is added drop-wise under agitation In system, and reaction
temperature is set to be no more than 5 DEG C.Continue to stir 20 min, heat preservation for standby use after completion of dropping.To in 2 L four-hole bottles Add 28
g（0.34mol）Cuprous bromide, 80 mL hydrobromic acids（40%）, it is stirred vigorously under normal temperature, above-mentioned diazo liquid is poured into In four
mouthfuls of reaction bulbs, reaction has a large amount of gases to produce, and diazo liquid continues to stir 20 min after adding, point liquid, lower oor's organic
phase alkali Simple distillation obtains the yellow liquid product neighbour g of 5 bromine benzotri uoride 394, G/C content after being washed till neutral, washing：
99%, yield：91%.On The layer mutually recyclable hydrobromic acid of water and cuprous bromide are applied mechanically.
（2）, nitration reaction Unexaminded application
To the 237 g concentrated sulfuric acids under normal gentle agitation（98%）In be slowly added to 122 g fuming nitric aicds, be made into mixed acid nitration.50-60
To the upper step product neighbour g of 5 bromine benzotri uoride 390 is slowly added dropwise in nitration mixture at DEG C, rear insulated and stirred is nished,
GC detections are without raw material It is reaction end.Divide liquid, it is bromo- that upper organic phase simple distillation after alkali cleaning to neutral, washing
obtains glassy yellow liquid nitro compounds 2- The g of 5- nitro-tri uoromethyl toluenes 454, G/C content：95%, yield：93%.
To sequentially adding 300 mL methyl alcohol, 284 g nitro products, the g of Raney Ni 20, adjacent nitre in 1 L high-pressure hydrogenation reactors The g of base
aniline 1.0.Air 3-4 times in kettle is replaced with hydrogen, pressure then in 0.8-1.0Mpa, at a temperature of 80-90 DEG C Reacted, untill reaction no longer inhales
hydrogen.Catalyst, methanol removal, removing moisture, simple steaming are ltered after reaction solution cooling The bromo- g of 3- 5-tri uoromethylanilines 248 of
weak yellow liquid amino substance 4-, G/C content are obtained after evaporating：95%, yield：98%.Raney Ni and Solvent methanol is recyclable to be applied
mechanically.
1 L stainless steel cauldrons are cooled to -10 DEG C, successively to adding 380 g anhydrous hydro uoric acids, the anhydrous uorinations of 5.8g in kettle Amino
substance is walked on potassium, 248 g, then 72.4 g natrium nitrosums is added slowly in reaction system in batches under agitation, and made anti- System
temperature is answered no more than 5 DEG C, 30 min of stirring are continued after adding makes diazo-reaction complete.It is warming up to 60 DEG C and
maintains this temperature Degree, uorination diazol starts slowly to decompose and release gas, and tail gas is by alkali liquor absorption after a cooling buffer
unit.Reaction is no longer Reacted after releasing gas and terminated, 0 DEG C will be cooled to after reclaiming by unnecessary hydro uoric acid in kettle, be
neutralized to 10%KOH solution is added in kettle Neutrality, steam distillation obtains the g of colourless liquid 2-bromo-5- uorobenzotri uoride crude product 225,
through lling extract recti cation post recti cation under vacuum, in 110 DEG C of -120 DEG C of cuts are collected under 40mmHg and obtains the g of colourless
transparent liquid 204.5, i.e. 2-bromo-5- uorobenzotri uoride product, GC contains Amount：99%, yield：85%.The hydro uoric acid of recovery can be applied
mechanically after being processed into anhydrous hydro uoric acid through water removal.
Embodiment 2
（1）, sandmeyer bromo-reaction

To 970 mL hydrobromic acids under normal gentle agitation（40%）In be slowly added to 308 g（1.9mol）O-tri uoromethyl aniline, plus It is cooled with an ice bath
after complete to 0 DEG C.By 140 g（2.03mol）Natrium nitrosum is dissolved in 325 mL water, is slowly dropped under agitation In reaction system, and reaction
temperature is set to be no more than 5 DEG C.Continue to stir 20 min, heat preservation for standby use after completion of dropping.To tetra- mouthfuls of 2 L 23.5 g
are added in bottle（0.34mol）Cuprous bromide, 65 mL hydrobromic acids（40%）, it is stirred vigorously under normal temperature, by above-mentioned diazo liquid
It is poured into four mouthfuls of reaction bulbs, reaction there are a large amount of gases to produce, diazo liquid continues to stir 20 min after adding, and point
liquid, lower oor has Simple distillation obtains the yellow liquid product neighbour g of 5 bromine benzotri uoride 386, G/C content after machine phase alkali
cleaning to neutral, washing：99%, yield： 89%.The recyclable hydrobromic acid of upper strata aqueous phase and cuprous bromide are applied mechanically.
（2）, nitration reaction
To the 260 g concentrated sulfuric acids under normal gentle agitation（98%）In be slowly added to 120 g fuming nitric aicds, be made into mixed acid
Unexaminded nitration.50-60
application
To the upper step product neighbour g of 5 bromine benzotri uoride 390 is slowly added dropwise in nitration mixture at DEG C, rear insulated and stirred is nished,
GC detections are without raw material It is reaction end.Divide liquid, it is bromo- that upper organic phase simple distillation after alkali cleaning to neutral, washing
obtains glassy yellow liquid nitro compounds 2- The g of 5- nitro-tri uoromethyl toluenes 450.4, G/C content：95%, yield：92%.
To 300 mL methyl alcohol are sequentially added in 1 L high-pressure hydrogenation reactors, nitro product is walked on 284 g, the g of Raney Ni 20, The g of piperazine
1.0.Air 3-4 times in kettle is replaced with hydrogen, pressure then in 0.8-1.0Mpa, is entered at a temperature of 80-90 DEG C Row reaction, untill reaction no longer
inhales hydrogen.Catalyst, methanol removal, removing moisture, simple distillation are ltered after reaction solution cooling The bromo- g of 3- 5-
tri uoromethylanilines 250 of weak yellow liquid amino substance 4-, G/C content are obtained afterwards：95%, yield：98.8%.Raney Ni and Solvent methanol is
recyclable to be applied mechanically.
1 L stainless steel cauldrons are cooled to -10 DEG C, successively to adding 450 g anhydrous hydro uoric acids, the anhydrous uorinations of 6.0g in kettle Amino
substance is walked on potassium, 248 g, then 75.5g natrium nitrosums is added slowly in reaction system in batches under agitation, and made anti- System
temperature is answered no more than 5 DEG C, 30 min of stirring are continued after adding makes diazo-reaction complete.It is warming up to 60 DEG C and
maintains this temperature Degree, uorination diazol starts slowly to decompose and release gas, and tail gas is by alkali liquor absorption after a cooling buffer
unit.Reaction is no longer Reacted after releasing gas and terminated, 0 DEG C will be cooled to after reclaiming by unnecessary hydro uoric acid in kettle, be
neutralized to 10%KOH solution is added in kettle Neutrality, steam distillation obtains the g of colourless liquid 2-bromo-5- uorobenzotri uoride crude product 233,
through lling extract recti cation post recti cation under vacuum, in 110 DEG C of -120 DEG C of cuts are collected under 40mmHg and obtains the g of colourless
transparent liquid 209, i.e. 2-bromo-5- uorobenzotri uoride product, GC contains Amount：99%, yield：86.8%.The hydro uoric acid of recovery can be applied
mechanically after being processed into anhydrous hydro uoric acid through water removal.
The foregoing is only presently preferred embodiments of the present invention, be not intended to limit the invention, it is all it is of the invention spirit and Any
modi cation, equivalent and improvement for being made within principle etc., are all contained within protection scope of the present invention.
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Cited By (1)
Publication number Priority date Publication date Assignee Title
CN109369414A * 2018-11-15 2019-02-22 江苏中旗科技股份有 A method of preparing the chloro- 2,4 di uorobenzene amine of Te ubenzuron
限公司 intermediate 3,5- bis-
Family To Family Citations
* Cited by examiner, † Cited by third party, ‡ Family to family citation
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Priority And Related Applications
Priority Applications (1)
Application Priority date Filing date Title
CN201710002434.9A 2017-01-03 2017-01-03 Synthesis method of 2-bromo-5- uorobenzotri uoride
Applications Claiming Priority (1)
Application Filing date Title
CN201710002434.9A 2017-01-03 Synthesis method of 2-bromo-5- uorobenzotri uoride
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2017-06-30 PB01 Publication
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2017-07-25 SE01 Entry into force of request for substantive examination
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2019-12-03 TA01 Transfer of patent application right Effective date of registration: 20191113
Address after: 312369 No.8, Beitang East Road, Shangyu economic and Technological
Development Zone, Hangzhou Bay, Shaoxing City, Zhejiang Province
Applicant after: Wei Zhejiang Huaxin materials Limited by Share Ltd

Address before: 322109, No. 128, industrial road, Weishan Town, Jinhua, Zhejiang,
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Concepts
machine-extracted Download Filter table
Name Image Sections Count Query match
synthetic method title,claims,abstract,description 29 0.000
[F-].FC(C1=CC=CC=C1)(F)F title,abstract,description 7 0.000

F-
bromine title,abstract 3 0.000
Br Br
chemical reactions claims,abstract,description 64 0.000
2-(tri uoromethyl)aniline claims,abstract,description 22 0.000

F
F
NH2
nitration reactions claims,abstract,description 13 0.000
raw materials claims,abstract,description 12 0.000
products claims,abstract,description 11 0.000
catalytic claims,abstract,description 8 0.000
bromo group claims,abstract,description 6 0.000
* Br
materials claims,abstract,description 6 0.000
bromination reactions claims,abstract,description 4 0.000
initiatory claims,abstract,description 4 0.000
Degeneriaceae claims,description 39 0.000
1-bromo-4- uoro-2-(tri uoromethyl)benzene claims,description 37 0.000

Br
F
F
F
liquids claims,description 33 0.000
HF claims,description 18 0.000
HF
gases claims,description 17 0.000
hydro uoric acid claims,description 16 0.000
primary amino group claims,description 15 0.000
* NH2
sodium claims,description 13 0.000
Na
solutions claims,description 13 0.000
substances claims,description 13 0.000
alkali claims,description 12 0.000
methanol claims,description 12 0.000
OH
acids claims,description 11 0.000
catalysts claims,description 11 0.000
hydrogen bromide claims,description 11 0.000
HBr
simple distillation claims,description 11 0.000
FC(C1=CC=CC=C1)(F)F.[Br] claims,description 10 0.000

Br
F Unexaminded application
F
diazo group claims,description 10 0.000
+ -
* N N
methanol claims,description 10 0.000
water claims,description 10 0.000
washing claims,description 9 0.000
Copper(I) bromide claims,description 8 0.000
Br Cu
Diazinon claims,description 8 0.000
O N
S
P
O N
O
cooling claims,description 8 0.000
hydrogen claims,description 8 0.000
nickel claims,description 8 0.000
nitro derivatives claims,description 8 0.000
solvents claims,description 8 0.000
stirring claims,description 8 0.000

Sulfuric acid claims,description 7 0.000
O
OH
S
HO
O
cleaning claims,description 7 0.000
dehalogenation reactions claims,description 7 0.000
organic phases claims,description 7 0.000
uorination reactions claims,description 6 0.000
inhibitors claims,description 6 0.000
inhibitory effects claims,description 6 0.000
ortho-nitraniline claims,description 6 0.000
addition claims,description 5 0.000
mixtures claims,description 5 0.000
phases claims,description 5 0.000
sulfuric acid claims,description 5 0.000
Potassium uoride claims,description 4 0.000

- +
F K
absorption reactions claims,description 4 0.000
crude products claims,description 4 0.000

H H
hydrogen atoms claims,description 4 0.000
* H
hydrogenation reactions claims,description 4 0.000
potassium uoride claims,description 4 0.000
potassium hydroxide claims,description 4 0.000
potassium hydroxide claims,description 4 0.000
preparation methods claims,description 4 0.000
stainless steel claims,description 4 0.000
stainless steel claims,description 4 0.000
steam distillation claims,description 4 0.000

warming claims,description 4 0.000
Potassium nitrate K
+ claims,description 3 0.000
- -
O O
+
N
aqueous solutions claims,description 3 0.000
chemical substances by application claims,description 3 0.000
piperazine NH claims,description 3 0.000
HN
salts claims,description 3 0.000
sodium chloride claims,description 3 0.000
Triphenyl phosphate claims,description 2 0.000

O O
O O
Triphenyl phosphite claims,description 2 0.000

O
O P
llers claims,description 2 0.000
morpholine claims,description 2 0.000
NH
morpholine claims,description 2 0.000
sodium nitrate claims,description 2 0.000

hydrogen bromide claims 2 0.000
Sandmeyer reactions abstract,description 4 0.000
uoro group abstract,description 4 0.000
* F
bromine atom abstract,description 3 0.000
Br
doping agents abstract,description 3 0.000
species abstract,description 3 0.000
synthesis reactions abstract,description 2 0.000
Show all concepts from the description section
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CN106905104A - A Kind of Synthetic Method of The Fluoride Trifluoro Toluene of 2 Bromine 5 - Google Patents PDF

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26/12/2020 CN106905104A - A kind of synthetic method of the fluoride trifluoro toluene of 2 bromine 5 - Google Patents

A kind of synthetic method of the uoride tri uoro toluene of 2 bromine 5

Classi cations Worldwide applications

View 2 more classi cations Application CN201710002434.9A events

2017-01-03 Application led by 浙江巍华化工有限公司

2017-01-03 Priority to CN201710002434.9A

2017-06-30 Publication of CN106905104A

2019-12-24 Application granted

2019-12-24 Publication of CN106905104B

Info: Patent citations (3), Non-patent citations (1), Cited by (1),

External links: Espacenet, Global Dossier, Discuss

Claims (10) Hide Dependent

（1）Sandmeyer bromination reaction

（3）Catalytic hydrogenating reduction reacts

A kind of synthetic method of 2-bromo-5- uorobenzotri uoride

The content of the invention

Reaction mechanism of the present invention is as follows：

（1）Sandmeyer bromination reaction

（3）Catalytic hydrogenating reduction reacts

（1）, sandmeyer bromo-reaction

（2）, nitration reaction Unexaminded application

（3）Catalytic hydrogenating reduction reacts

（1）, sandmeyer bromo-reaction

（2）, nitration reaction

（3）Catalytic hydrogenating reduction reacts

Patent Citations (3)

Publication number Priority date Publication date Assignee Title

Family To Family Citations

* Cited by examiner, † Cited by third party

Non-Patent Citations (1)

刘雅茹等: "3-三氟甲基-4-氰基苯胺的合成", 《广东药学院学报》 *

* Cited by examiner, † Cited by third party

Publication number Priority date Publication date Assignee Title

Family To Family Citations

* Cited by examiner, † Cited by third party, ‡ Family to family citation

Publication Publication Date Title

CN102405203B 2015-04-08 Process for preparation of 2,3,3,3-tetra uoropropene

JP5704264B2 2015-04-22 Method for producing 2,3,3,3-tetra uoropropene Unexaminded application

US7763759B2 2010-07-27 Continuous process for the manufacture of nitrobenzene

US8076505B2 2011-12-13 Process of preparing derivatives of 1-(2-halobiphenyl-4-yl)-cyclopropanecarboxylic acid

US20040077901A1 2004-04-22 Process for the synthesis of tri uorophenylacetic acids

CN101675017B 2013-09-25 Method for producing 3,3,3-tri uoropropyne

CN102001910B 2013-11-06 Method for preparing 2,3,3,3-tetra uoropropene

TW422813B 2001-02-21 Process for manufacture of lithium hexa uorophosphate

US2342101A 1944-02-22 Preparation of dihydro mucononitrile and product

CN103172571B 2015-07-01 New preparation method of insect repellent albendazole

EP2280925A1 2011-02-09 Process for the manufacture of nitropropanes

US5294742A 1994-03-15 Process for preparing 3,5-di uoroaniline

JP2010013465A 2010-01-21 Method for producing 4-aminodiphenylamine

JP4872668B2 2012-02-08 Process for producing 2-amino-5-iodobenzoic acid

CN103664511B 2015-07-08 Preparation method of 5-bromo-1,3-dichloro-2- uorobenzene

Priority And Related Applications

Priority Applications (1)

Application Priority date Filing date Title

CN201710002434.9A 2017-01-03 2017-01-03 Synthesis method of 2-bromo-5- uorobenzotri uoride

Applications Claiming Priority (1)

Application Filing date Title

CN201710002434.9A 2017-01-03 Synthesis method of 2-bromo-5- uorobenzotri uoride

Date Code Title Description

2017-06-30 PB01 Publication

2017-07-25 SE01 Entry into force of request for substantive examination

2017-07-25 SE01 Entry into force of request for substantive examination

Applicant after: Wei Zhejiang Huaxin materials Limited by Share Ltd