CN107162894A - The post-treatment new process of the chlorobenzoic acid of 5 bromine 2 - Google Patents
The post-treatment new process of the chlorobenzoic acid of 5 bromine 2 Download PDFInfo
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- CN107162894A CN107162894A CN201710502121.XA CN201710502121A CN107162894A CN 107162894 A CN107162894 A CN 107162894A CN 201710502121 A CN201710502121 A CN 201710502121A CN 107162894 A CN107162894 A CN 107162894A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/093—Preparation of carboxylic acids or their salts, halides or anhydrides by hydrolysis of —CX3 groups, X being halogen
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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
Abstract
The present invention relates to a kind of post-treatment new process of the chlorobenzoic acid of 5 bromine 2, comprise the following steps：A) under catalyst action, it is that the bromine benzotrichloride of 2 chlorine 5 is made in reaction raw materials by 2 chlorobenzotrichlorides and bromine, then adds organic acid, heating response is reacted after terminating, concentration and recovery organic acid；B) to step A) in concentrate in add water crystallization, filtering obtains the chlorobenzoic acid crude product of 5 bromine 2.The present invention successfully solves reaction in the prior art and produces a large amount of H2SO4, wastewater problem containing high concentrated acid and salt of HCl, iron chloride or ferric bromide etc. and the problems such as potential safety hazard, safety and environmental protection is economical and practical while the organic acid of concentration and recovery can be reused directly.
Description
Technical field
The present invention relates to technical field of organic synthesis, and in particular to a kind of post-treatment new process of the bromo- 2- chlorobenzoic acids of 5-.
Background technology
The bromo- 2- chlorobenzoic acids of 5- are the initiation materials for synthesizing antidiabetic medicine dapagliflozin (Dapagliflozin).
Publication No. discloses a kind of synthetic method of the bromo- 2- chlorobenzoic acids of 5- for the A of CN 105622382 patent of invention,
Using 2- chlorobenzotrichlorides as raw material, through bromo, hydrolysis, the bromo- 2- chlorobenzoic acids of 5- are obtained.The route raw material is cheap and easy to get,
Total recovery is high, but post-processes the problem of producing the acid and high salinity waste water of sulfur acid, hydrochloric acid and hydrobromic acid.Existing processing should
Method for waste water is first to be neutralized with piece alkali, then water is evaporated, and obtains the salt-mixtures such as a large amount of sulfur acid sodium, sodium chloride and iron oxide
Solid waste, the solid waste is difficult to recycle, and processing cost is very big, directly influences the economic benefit and social benefit of product.Although
The aftertreatment technology of use water direct hydrolysis is indicated in that patent, and it is most convenient that the post-processing approach, which is seemed, but under the conditions of this
Hydrolysis be centralization type, reaction temperature be less than 100 DEG C when, raw material is hardly hydrolyzed, even in 100 DEG C react 20 hours,
Feed stock conversion, once temperature rises to 110 DEG C or so, drastically reacts also less than 10%, can release a large amount of hydrogen chloride gas.Such as
Fruit adds substantial amounts of water as solvent, rises not get on again to disperse temperature in heat, reaction.The experiment is relatively put down in the lab scale stage
Surely, but when carrying out pilot scale, occur very serious slug accident, be not suitable for further amplification production.Therefore, it is necessary to further exploitation
New safety and the aftertreatment technology of environmental protection, are economical and environmentally friendly required with meeting.
The content of the invention
The technical problems to be solved by the invention are to overcome the deficiencies in the prior art there is provided a kind of safety and the 5- of environmental protection
The post-treatment new process of bromo- 2- chlorobenzoic acids, solves waste present in prior art and safety problem.
To solve above technical problem, a kind of technical scheme that the present invention takes is：
A kind of post-treatment new process of the bromo- 2- chlorobenzoic acids of 5-, comprises the following steps：
A it is that the chloro- 5- bromines benzotrichlorides of 2- are made in reaction raw materials by 2- chlorobenzotrichlorides and bromine) under catalyst action,
Then organic acid is added, heating response is reacted after terminating, concentration and recovery organic acid；
B) to step A) in concentrate in add water crystallization, filtering obtains the bromo- 2- chlorobenzoic acids crude products of 5-.
Preferably, step A) in the chloro- 5- bromines benzotrichlorides of 2- and organic acid mol ratio be 1：(5~20).
It is further preferred that step A) in the chloro- 5- bromines benzotrichlorides of 2- and organic acid mol ratio be 1：(10~15).
Preferably, step A) in organic acid formic acid, trifluoroacetic acid, acetic acid, propionic acid, one kind in methanesulfonic acid or several
Kind.
It is further preferred that step A) in organic acid select acetic acid or propionic acid.
Preferably, step A) in reaction temperature be 100~150 DEG C, the reaction time be 10~30 hours.
It is further preferred that step A) in reaction temperature be 115~125 DEG C, the reaction time be 15~20 hours.
Preferably, step B) in after the volume that adds water of crystallization and concentration the volume ratio of remaining organic acid be (0.5~2.0)：
1。
It is further preferred that step B) in after the volume that adds water of crystallization and concentration remaining organic acid volume ratio for (1.0~
1.5)：1.
Preferably, step A) in reclaim organic acid can next time directly use.
Due to the use of above technical scheme, the present invention has the following advantages that compared with prior art：
The present invention carries out post-reaction treatment using organic acid, successfully solves reaction in the prior art and produces a large amount of H2SO4、
The problems such as wastewater problem containing high concentrated acid and salt such as HCl, iron chloride or ferric bromide and potential safety hazard, safety and environmental protection, simultaneously
The organic acid of concentration and recovery can be reused directly, economical and practical, the bromo- 2- chlorine of 5- obtained according to the preparation method of the present invention
Benzoic acid yield is more than 85%, and purity is more than 90%, and organic acid recovery rate is more than 50%.
Embodiment
The present invention is described in further details below in conjunction with specific embodiment.It should be understood that these embodiments are to be used to say
The bright basic principles, principal features and advantages of the present invention, and the present invention is not limited by the scope of following examples.Adopted in embodiment
Implementation condition can do further adjustment according to specific requirement, and unreceipted implementation condition is usually the bar in normal experiment
Part.
The invention provides a kind of post-treatment new process of the bromo- 2- chlorobenzoic acids of 5-, comprise the following steps：
A it is that the chloro- 5- bromines benzotrichlorides of 2- are made in reaction raw materials by 2- chlorobenzotrichlorides and bromine) under catalyst action,
Then organic acid is added, heating response is reacted after terminating, concentration and recovery organic acid；
B) to step A) in concentrate in add water crystallization, filtering obtains the bromo- 2- chlorobenzoic acids crude products of 5-.
In the present invention, catalyst is preferably iron sulfide (Fe2S3), ferrous sulfide (FeS), iron powder (Fe), ferric trichloride
(FeCl3), frerrous chloride (FeCl2), ferric bromide (FeBr3) and ferrous bromide (FeBr2) in one or more.
In the present invention, the mol ratio of 2- chlorobenzotrichlorides and bromine is preferably 1：(0.6~3.0), 2- chlorobenzotrichlorides
Mol ratio with catalyst is preferably 1：(0.01~0.2).
In the present invention, the reaction temperature of 2- chlorobenzotrichlorides and bromine is preferably -10~100 DEG C, and the reaction time is preferred
For 3~30 hours.
In the present invention, step A) in the chloro- 5- bromines benzotrichlorides of 2- and organic acid mol ratio be 1：(5~20), more
Preferably 1：(10~15).
In the present invention, step A) in organic acid formic acid, trifluoroacetic acid, acetic acid, propionic acid, one kind in methanesulfonic acid
Or it is several, more preferably from acetic acid or propionic acid.
In the present invention, step A) in reaction temperature be 100~150 DEG C, the reaction time be 10~30 hours, more preferably
It it is 115~125 DEG C for reaction temperature, the reaction time is 15~20 hours.
In the present invention, step B) in after the volume that adds water of crystallization and concentration remaining organic acid volume ratio for (0.5~
2.0)：1, more preferably (1.0~1.5)：1.
In the present invention, step A) in reclaim organic acid can next time directly use.
The present invention can also will add solvent in the bromo- 2- chlorobenzoic acids crude products of 5-, recrystallized, obtain 5- after purification
Bromo- 2- chlorobenzoic acids.
Embodiment 1
At room temperature, 46g solid 2- chlorobenzotrichlorides (0.2mol, 1eq), 50mL dichloromethanes are added into 250mL reaction bulbs
Dissolved clarification under alkane, magnetic agitation, adds 5.92g FeBr3(0.02mol, 0.10eq), is then added dropwise 35.2g Br2(0.22mol,
1.1eq), 25-30 DEG C of reaction 6h is maintained, after reaction terminates, be concentrated under reduced pressure the Br for removing solvent and excess2。
180g acetic acid (3.0mol, 15eq) is added, 110 DEG C of reaction 15h is then heated to, after reaction terminates, is cooled to 60
Below DEG C, be concentrated under reduced pressure recovery acetic acid 120g (rate of recovery 67%).
90g water is added into system, being warming up to 80 DEG C is completely dissolved solid, is then gradually cooled to after 15 DEG C, filtering,
50mL water washing filter cakes, dry to obtain off-white color crude product 42.0g, yield 89.2%；HPLC 95.1%.
The off-white powder that the present invention is obtained to the present embodiment carries out magnetic resonance detection, and hydrogen modal data is as follows：1H NMR
(CDCl3, 400MHz)：δ 10.16 (b, 1H), 8.13 (s, 1H), 7.58 (d, J=8.0Hz, 1H), 7.35 (d, J=8.0Hz,
1H).From hydrogen modal data, the off-white powder that the present embodiment is obtained is the bromo- 2- chlorobenzoic acids of 5-.
Embodiment 2
At room temperature, 46g solids o-chlorotrichlorotoluene (0.2mol, 1eq), 50mL dichloromethanes are added into 250mL reaction bulbs
Dissolved clarification under alkane, magnetic agitation, adds 1.12g Fe powder (0.02mol, 0.10eq), and 35.2g Br are then added dropwise2(0.22mol,
1.1eq), 25-30 DEG C of reaction 6h is maintained, after reaction terminates, be concentrated under reduced pressure the Br for removing solvent and excess2。
120g propionic acid (2.0mol, 10eq) is added, 120 DEG C of reaction 20h is then heated to, after reaction terminates, is cooled to 60
Below DEG C, be concentrated under reduced pressure recovery propionic acid 60g (rate of recovery 50%).
80g water is added into system, being warming up to 80 DEG C is completely dissolved solid, is then gradually cooled to after 15 DEG C, filtering,
50mL water washing filter cakes, dry to obtain light grey crude product 41.7g, yield 88.5%；HPLC 94.7%.
The light gray solid that the present invention is obtained to the present embodiment carries out magnetic resonance detection,1H NMR are consistent with example 1.
Embodiment 3
At room temperature, 46g solids o-chlorotrichlorotoluene (0.2mol, 1eq), 50mL dichloromethanes are added into 250mL reaction bulbs
Dissolved clarification under alkane, magnetic agitation, adds 5.92g FeBr3(0.01mol, 0.05eq), is then added dropwise 35.2g Br2(0.22mol,
1.1eq), 25-30 DEG C of reaction 6h is maintained, after reaction terminates, be concentrated under reduced pressure the Br for removing solvent and excess2。
The acetic acid (2.0mol, 10eq) that 120g embodiments 1 are reclaimed is added, 110 DEG C of reaction 15h, reaction knot are then heated to
Shu Hou, is cooled to less than 60 DEG C, and be concentrated under reduced pressure recovery of acetic acid 60g (rate of recovery 50%).
80g water is added into system, being warming up to 80 DEG C is completely dissolved solid, is then gradually cooled to after 15 DEG C, filtering,
50mL water washing filter cakes, dry to obtain off-white color crude product 40.8g, yield 86.6%；HPLC 93.9%.
The off-white powder that the present invention is obtained to the present embodiment carries out magnetic resonance detection,1H NMR are consistent with example 1.
The present invention is described in detail above, the explanation of embodiment be only intended to help to understand the present invention method and
Its core concept, its object is to allow the personage for being familiar with this art to understand present disclosure and implement according to this, and
It can not be limited the scope of the invention with this.Any equivalent change or modification in accordance with the spirit of the invention, should all contain
Cover within protection scope of the present invention.
Claims (10)
1. a kind of post-treatment new process of the bromo- 2- chlorobenzoic acids of 5-, it is characterised in that：Comprise the following steps：
A it is that the chloro- 5- bromines benzotrichlorides of 2- are made in reaction raw materials by 2- chlorobenzotrichlorides and bromine, then) under catalyst action
Organic acid is added, heating response is reacted after terminating, concentration and recovery organic acid；
B) to step A) in concentrate in add water crystallization, filtering obtains the bromo- 2- chlorobenzoic acids crude products of 5-.
2. the post-treatment new process of the bromo- 2- chlorobenzoic acids of 5- according to claim 1, it is characterised in that：The step A)
In the chloro- 5- bromines benzotrichlorides of 2- and organic acid mol ratio be 1：(5~20).
3. the post-treatment new process of the bromo- 2- chlorobenzoic acids of 5- according to claim 2, it is characterised in that：The step A)
In the chloro- 5- bromines benzotrichlorides of 2- and organic acid mol ratio be 1：(10~15).
4. the post-treatment new process of the bromo- 2- chlorobenzoic acids of 5- according to claim 1, it is characterised in that：The step A)
In organic acid formic acid, trifluoroacetic acid, acetic acid, propionic acid, the one or more in methanesulfonic acid.
5. the post-treatment new process of the bromo- 2- chlorobenzoic acids of 5- according to claim 4, it is characterised in that：The step A)
In organic acid select acetic acid or propionic acid.
6. the post-treatment new process of the bromo- 2- chlorobenzoic acids of 5- according to claim 1, it is characterised in that：The step A)
In reaction temperature be 100~150 DEG C, the reaction time be 10~30 hours.
7. the post-treatment new process of the bromo- 2- chlorobenzoic acids of 5- according to claim 6, it is characterised in that：The step A)
In reaction temperature be 115~125 DEG C, the reaction time be 15~20 hours.
8. the post-treatment new process of the bromo- 2- chlorobenzoic acids of 5- according to claim 1, it is characterised in that：The step B)
The volume ratio of remaining organic acid is (0.5~2.0) after volume that middle crystallization adds water and concentration：1.
9. the post-treatment new process of the bromo- 2- chlorobenzoic acids of 5- according to claim 8, it is characterised in that：The step B)
The volume ratio of remaining organic acid is (1.0~1.5) after volume that middle crystallization adds water and concentration：1.
10. the post-treatment new process of the bromo- 2- chlorobenzoic acids of 5- according to claim 1, it is characterised in that：The step A)
The organic acid of middle recovery can be used directly next time.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710502121.XA CN107162894A (en) | 2017-06-27 | 2017-06-27 | The post-treatment new process of the chlorobenzoic acid of 5 bromine 2 |
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| CN201710502121.XA CN107162894A (en) | 2017-06-27 | 2017-06-27 | The post-treatment new process of the chlorobenzoic acid of 5 bromine 2 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110590541A (en) * | 2019-10-16 | 2019-12-20 | 吕东 | Preparation method of 5-bromo-2-chlorobenzoic acid |
| CN111620778A (en) * | 2020-05-28 | 2020-09-04 | 吴赣药业（苏州）有限公司 | Preparation method of 5-bromo-2-chlorobenzoic acid |
| CN112979448A (en) * | 2021-03-01 | 2021-06-18 | 苏州小栗医药科技有限公司 | Preparation method of high-selectivity 5-bromo-2-chlorobenzoic acid |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105622382A (en) * | 2016-02-23 | 2016-06-01 | 苏州天马精细化学品股份有限公司 | Synthesis method of 5-bromo-2-chloro benzoic acid |
-
2017
- 2017-06-27 CN CN201710502121.XA patent/CN107162894A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105622382A (en) * | 2016-02-23 | 2016-06-01 | 苏州天马精细化学品股份有限公司 | Synthesis method of 5-bromo-2-chloro benzoic acid |
Non-Patent Citations (1)
| Title |
|---|
| 魏文德等: "13.2.3 生产方法", 《有机化工原料大全（第四卷）》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110590541A (en) * | 2019-10-16 | 2019-12-20 | 吕东 | Preparation method of 5-bromo-2-chlorobenzoic acid |
| CN111620778A (en) * | 2020-05-28 | 2020-09-04 | 吴赣药业（苏州）有限公司 | Preparation method of 5-bromo-2-chlorobenzoic acid |
| CN112979448A (en) * | 2021-03-01 | 2021-06-18 | 苏州小栗医药科技有限公司 | Preparation method of high-selectivity 5-bromo-2-chlorobenzoic acid |
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Application publication date: 20170915 |