CN108558597A - The synthetic method of 5 bromine benzotrifluoride between a kind of highly effective - Google Patents
The synthetic method of 5 bromine benzotrifluoride between a kind of highly effective Download PDFInfo
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- CN108558597A CN108558597A CN201810582583.1A CN201810582583A CN108558597A CN 108558597 A CN108558597 A CN 108558597A CN 201810582583 A CN201810582583 A CN 201810582583A CN 108558597 A CN108558597 A CN 108558597A
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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
- C07C17/10—Preparation of halogenated hydrocarbons by replacement by halogens of hydrogen atoms
- C07C17/12—Preparation of halogenated hydrocarbons by replacement by halogens of hydrogen atoms in the ring of aromatic compounds
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/38—Separation; Purification; Stabilisation; Use of additives
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Abstract
The invention discloses a kind of synthetic methods of 5 bromine benzotrifluoride between highly effective, are as follows：(1) acetic acid and water are added in the reaction vessel, 98% sulfuric acid is then added dropwise；(2) benzotrifluoride is added, and sodium bromide is added in batches, temperature when control feeds is no more than 45 DEG C；(3) it waits after the completion of reacting, separates organic layer A after the temperature of charge in container is cooled to 30 DEG C hereinafter, standing, while leaving water layer B；(4) it is primary that organic solvent extraction is added into water layer B, and separates organic layer C；(5) organic layer A and C are merged, and water is added into mixed solution, stood in separatory funnel after stirring and separate upper strata aqueous phase and lower organic layer；(6) organic layer obtained in step (5) is washed with NaOH aqueous solutions；(7) organic layer in step (6) is detached, is dried etc. again 5 bromine benzotrifluoride between can obtaining after operations.The present invention uses NaBrO3‑‑H2SO4‑‑CH3COOH systems are reacted, and the three wastes are low, and highly effective.
Description
Technical field
The present invention relates to medicine intermediate preparation, the synthetic method of 5 bromine benzotrifluoride between specifically a kind of highly effective.
Background technology
Between 5 bromine benzotrifluoride be synthesis medicine intermediate (TrifluoroMethyl)acetophenone and then synthesize miazines and antipsychotic
The raw material of class drug.
Current synthetic route is broadly divided into two kinds：(1) by trifluoromethylbenzene after nitrifying, restoring, then through Sandmeyer
Reaction synthesis；(2) 5 bromine benzotrifluoride between bromination preparation is directly carried out by bromine and trifluoromethylbenzene.Using its conjunction of first method
At route field, quantity of three wastes is big, and total recovery is low, industrially almost without practical value；Using second method its yield 50%
Left and right.This is because the passivation of trifluoromethyl, the direct required temperature of bromination is high, is easy to cause the water of trifluoromethyl
Solution.
Invention content
The purpose of the present invention is to provide a kind of three wastes content is low, and bromine trifluoro between the highly effective that can be carried out under low temperature
The synthetic method of toluene, to solve the problems mentioned in the above background technology.
To achieve the above object, the present invention provides the following technical solutions：
The synthetic method of 5 bromine benzotrifluoride, is as follows between a kind of highly effective：
(1) acetic acid and water are added in the reaction vessel, 98% sulfuric acid is then added dropwise and ensures safety；
(2) benzotrifluoride is added, and sodium bromide is added in batches, temperature when control feeds is no more than 45 DEG C, then protects
Sample detection raw material response situation after temperature reaction；
(3) it waits after the completion of reacting, separates organic layer A after the temperature of charge in container is cooled to 30 DEG C hereinafter, standing, together
When leave water layer B；
(4) it is primary that organic solvent extraction is added into water layer B, and separates organic layer C, and it is anti-that sour water layer given over to lower batch
At once it applies mechanically；
(5) organic layer A and C are merged, and water is added into mixed solution, stood and divide in separatory funnel after stirring
Go out upper strata aqueous phase and lower organic layer；
(6) organic layer obtained in step (5) is washed with the NaOH aqueous solutions of 2-4% and is adjusted to pH=7；
(7) organic layer in step (6) is detached again, and is dried overnight using anhydrous sodium sulfate, filtered later
Sodium sulphate is removed, filtrate normal pressure steams organic solvent and makees to apply mechanically when lower batch reaction, you can obtains a 5 bromine benzotrifluoride.
As a further solution of the present invention：The weight ratio of acetic acid, water and 98% sulfuric acid is (1-3) in the step (1):
1:(2-4)
As a further solution of the present invention：It is 1 that benzotrifluoride and sodium bromide in the step (2), which are weight ratio,:(1-
2)
As a further solution of the present invention：The weight ratio 2 of sodium bromide and 98% sulfuric acid in the step (2):(4-
6)。
As a further solution of the present invention：In the step (2) after the completion of charging at 40-50 DEG C insulation reaction 9-11
Hour.
As a further solution of the present invention：Mixing time in the step (5) is 9-11 minutes.
As a further solution of the present invention：The organic solvent is difluoromethane or Difluoroethane.
In actual mechanical process of the present invention, sodium bromate is substituted with potassium bromate and is reacted, the results showed that reaction yield and pure
Degree is apparent relatively low, and product needs rectification and purification.The oxidability for being primarily due to potassium bromate is too strong, easily leads to trifluoromethyl by oxygen
Change hydrolysis.
Compared with prior art, the beneficial effects of the invention are as follows：The present invention uses NaBrO3--H2SO4--CH3COOH systems
Reaction can be good at carrying out bromination to benzotrifluoride, and yield can reach 95% or more, analyzed by GC, purity up to 98% with
On, product of the invention can be used to other reactions after sloughing low boiling point solvent without rectifying.Present invention employs lower
Reaction temperature generates almost without hydrolysate.A certain amount of acetic acid is added in the present invention in the reaction system, it is ensured that process does not have
The smell of bromine generates, and the sour water after simultaneous reactions repeats the lower batch of practicality that feeds intake, and the three wastes have obtained good control, are a kind of high
Imitate practical synthetic method.
Specific implementation mode
Below in conjunction with the embodiment of the present invention, technical scheme in the embodiment of the invention is clearly and completely described,
Obviously, described embodiments are only a part of the embodiments of the present invention, instead of all the embodiments.Based in the present invention
Embodiment, every other embodiment obtained by those of ordinary skill in the art without making creative efforts, all
Belong to the scope of protection of the invention.
Embodiment 1
In the embodiment of the present invention, 460 grams of 920 grams of acetic acid and water are added in the reaction vessel, 98% sulfuric acid is then added dropwise
1380 grams ensure that safety, process can heat up, while paying attention to controlling rate of addition, ensure safety, avoid exploding.It is added dropwise to complete simultaneously
After being cooled to 30 DEG C, 500 grams of benzotrifluoride is added to reaction vessel, 518 grams of sodium bromide is added in stirring while in batches, controls
Temperature when charging is no more than 45 DEG C, after the completion of charging at 45 DEG C insulation reaction 10 hours；Sample detection raw material response situation.
After the completion of waiting for above-mentioned reaction, organic layer A is separated after the temperature of charge in container is cooled to 30 DEG C hereinafter, standing, is left simultaneously
Water layer B.Difluoromethane or the Difluoroethane extraction that 500ml-1000ml is added into water layer B are primary, and separate organic layer C,
And sour water layer is given over to when lower batch is reacted and is applied mechanically.Organic layer A and C are merged, and 1000ml is added into mixed solution
Water, stirring after ten minutes, you can removal reaction solution in remaining acetic acid；And in separatory funnel stand separate upper strata aqueous phase and
Lower organic layer.Above-mentioned organic layer is washed using 3% or so NaOH aqueous solutions and is adjusted to pH=7；Again by organic layer separation
Go out and be dried overnight using anhydrous sodium sulfate, later removal of sodium sulfate by filtration, filtrate normal pressure steams difluoromethane or difluoro second
Alkane (recovery), you can obtain about 735 grams of 5 bromine benzotrifluoride between product.G/C content is more than 98%.Yield 95.45%.
Embodiment 2
In the embodiment of the present invention, 460 grams of 460 grams of acetic acid and water are added in the reaction vessel, 98% sulfuric acid 920 is then added dropwise
Gram ensure safety, process can heat up, while pay attention to controlling rate of addition, ensure safety, avoid exploding.It is added dropwise to complete and cools down
To after 30 DEG C, 460 grams of benzotrifluoride is added to reaction vessel, 460 grams of sodium bromide, control charging is added in stirring while in batches
When temperature be no more than 45 DEG C, after the completion of charging at 45 DEG C insulation reaction 10 hours；Sample detection raw material response situation.It waits for
After the completion of stating reaction, organic layer A is separated after the temperature of charge in container is cooled to 30 DEG C hereinafter, standing, while leaving water layer
B.Difluoromethane or the Difluoroethane extraction that 500ml-1000ml is added into water layer B are primary, and separate organic layer C, and will
Sour water layer is applied mechanically when giving over to lower batch reaction.Organic layer A and C are merged, and the water of 1000ml is added into mixed solution,
Stirring is after ten minutes, you can remaining acetic acid in removal reaction solution；And it is stood in separatory funnel and separates upper strata aqueous phase and lower layer
Organic layer.Above-mentioned organic layer is washed using 3% or so NaOH aqueous solutions and is adjusted to pH=7；Organic layer is isolated simultaneously again
It is dried overnight using anhydrous sodium sulfate, later removal of sodium sulfate by filtration, filtrate normal pressure steams difluoromethane or Difluoroethane (returns
Receipts are applied mechanically), you can obtain about 455 grams of 5 bromine benzotrifluoride between product.G/C content is more than 98%.Yield 95.10%.
Embodiment 3
In the embodiment of the present invention, 460 grams of 1380 grams of acetic acid and water are added in the reaction vessel, 98% sulfuric acid is then added dropwise
1820 grams ensure that safety, process can heat up, while paying attention to controlling rate of addition, ensure safety, avoid exploding.It is added dropwise to complete simultaneously
After being cooled to 30 DEG C, 1092 grams of benzotrifluoride is added to reaction vessel, 546 grams of sodium bromide is added in stirring while in batches, controls
System charging when temperature be no more than 45 DEG C, after the completion of charging at 45 DEG C insulation reaction 10 hours；Sample detection raw material reacts feelings
Condition.After the completion of waiting for above-mentioned reaction, organic layer A is separated after the temperature of charge in container is cooled to 30 DEG C hereinafter, standing, is stayed simultaneously
Lower water layer B.Difluoromethane or the Difluoroethane extraction that 500ml-1000ml is added into water layer B are primary, and separate organic layer
C, and sour water layer is given over to when lower batch is reacted and is applied mechanically.Organic layer A and C are merged, and are added into mixed solution
The water of 1000ml, stirring is after ten minutes, you can remaining acetic acid in removal reaction solution；And it is stood in separatory funnel and separates upper layer
Water phase and lower organic layer.Above-mentioned organic layer is washed using 3% or so NaOH aqueous solutions and is adjusted to pH=7；It again will be organic
Layer separation is gone out and is dried overnight using anhydrous sodium sulfate, later removal of sodium sulfate by filtration, filtrate normal pressure steam difluoromethane or
Difluoroethane (recovery), you can obtain about 910 grams of 5 bromine benzotrifluoride between product.G/C content is more than 99%.Yield
95.31%.
It is obvious to a person skilled in the art that invention is not limited to the details of the above exemplary embodiments, Er Qie
In the case of without departing substantially from spirit or essential attributes of the invention, the present invention can be realized in other specific forms.Therefore, no matter
From the point of view of which point, the present embodiments are to be considered as illustrative and not restrictive, and the scope of the present invention is by appended power
Profit requires rather than above description limits, it is intended that all by what is fallen within the meaning and scope of the equivalent requirements of the claims
Variation is included within the present invention.
In addition, it should be understood that although this specification is described in terms of embodiments, but not each embodiment is only wrapped
Containing an independent technical solution, this description of the specification is merely for the sake of clarity, and those skilled in the art should
It considers the specification as a whole, the technical solutions in the various embodiments may also be suitably combined, forms those skilled in the art
The other embodiment being appreciated that.
Claims (7)
1. the synthetic method of 5 bromine benzotrifluoride between a kind of highly effective, which is characterized in that be as follows：
(1) acetic acid and water are added in the reaction vessel, 98% sulfuric acid is then added dropwise and ensures safety；
(2) benzotrifluoride is added, and sodium bromide is added in batches, temperature when control feeds is no more than 45 DEG C, and then heat preservation is anti-
It should rear sample detection raw material response situation；
(3) it waits after the completion of reacting, separates organic layer A after the temperature of charge in container is cooled to 30 DEG C hereinafter, standing, stay simultaneously
Lower water layer B；
(4) when it is primary that organic solvent extraction being added into water layer B, and separates organic layer C, and sour water layer being given over to lower batch reaction
It applies mechanically；
(5) organic layer A and C are merged, and water is added into mixed solution, stood and separate in separatory funnel after stirring
Layer water phase and lower organic layer；
(6) organic layer obtained in step (5) is washed with the NaOH aqueous solutions of 2-4% and is adjusted to pH=7；
(7) organic layer in step (6) is detached again, and is dried overnight using anhydrous sodium sulfate, later filtering removal
Sodium sulphate, filtrate normal pressure steam organic solvent and make to apply mechanically when lower batch reaction, you can obtain a 5 bromine benzotrifluoride.
2. the synthetic method of 5 bromine benzotrifluoride between highly effective according to claim 1, which is characterized in that the step
(1) weight ratio of acetic acid, water and 98% sulfuric acid is (1-3) in:1:(2-4).
3. the synthetic method of 5 bromine benzotrifluoride between highly effective according to claim 1, which is characterized in that the step
(2) it is 1 that benzotrifluoride and sodium bromide in, which are weight ratio,:(1-2).
4. the synthetic method of 5 bromine benzotrifluoride between highly effective according to claim 1 or 3, which is characterized in that described
The weight ratio 2 of sodium bromide and 98% sulfuric acid in step (2):(4-6).
5. the synthetic method of 5 bromine benzotrifluoride between highly effective according to claim 4, which is characterized in that the step
(2) in after the completion of charging insulation reaction 9-11 hours at 40-50 DEG C.
6. the synthetic method of 5 bromine benzotrifluoride between highly effective according to claim 1, which is characterized in that the step
(5) mixing time in is 9-11 minutes.
7. the synthetic method of 5 bromine benzotrifluoride between highly effective according to claim 1, which is characterized in that described organic
Solvent is difluoromethane or Difluoroethane.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4155940A (en) * | 1977-02-25 | 1979-05-22 | Bayer Aktiengesellschaft | M-Bromo-benzotrifluorides |
| CN104311386A (en) * | 2014-11-05 | 2015-01-28 | 江苏辉丰农化股份有限公司 | Method for preparing 2-bromine-5-fluorobenzotrifluoride |
| CN105801348A (en) * | 2016-04-20 | 2016-07-27 | 江苏中能化学科技股份有限公司 | 3-bromobenzotrifluoride and preparation method thereof |
| CN106278837A (en) * | 2015-05-28 | 2017-01-04 | 联化科技（台州）有限公司 | The Preparation Method And Their Intermediate of o-trifluoromethyl-4-halogenated benzaldehyde |
-
2018
- 2018-06-07 CN CN201810582583.1A patent/CN108558597A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4155940A (en) * | 1977-02-25 | 1979-05-22 | Bayer Aktiengesellschaft | M-Bromo-benzotrifluorides |
| CN104311386A (en) * | 2014-11-05 | 2015-01-28 | 江苏辉丰农化股份有限公司 | Method for preparing 2-bromine-5-fluorobenzotrifluoride |
| CN106278837A (en) * | 2015-05-28 | 2017-01-04 | 联化科技（台州）有限公司 | The Preparation Method And Their Intermediate of o-trifluoromethyl-4-halogenated benzaldehyde |
| CN105801348A (en) * | 2016-04-20 | 2016-07-27 | 江苏中能化学科技股份有限公司 | 3-bromobenzotrifluoride and preparation method thereof |
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Application publication date: 20180921 |