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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- 238000000034 method Methods 0.000 title claims abstract description 20
- 230000008569 process Effects 0.000 title claims abstract description 17
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 title claims abstract description 11
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 title claims abstract description 9
- 229910052794 bromium Inorganic materials 0.000 title claims abstract description 9
- IKCLCGXPQILATA-UHFFFAOYSA-N 2-chlorobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1Cl IKCLCGXPQILATA-UHFFFAOYSA-N 0.000 title abstract 3
- 238000006243 chemical reaction Methods 0.000 claims abstract description 31
- 150000007524 organic acids Chemical class 0.000 claims abstract description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 18
- 238000011084 recovery Methods 0.000 claims abstract description 15
- MFHPYLFZSCSNST-UHFFFAOYSA-N 1-chloro-2-(trichloromethyl)benzene Chemical class ClC1=CC=CC=C1C(Cl)(Cl)Cl MFHPYLFZSCSNST-UHFFFAOYSA-N 0.000 claims abstract description 11
- 238000002425 crystallisation Methods 0.000 claims abstract description 9
- 230000008025 crystallization Effects 0.000 claims abstract description 9
- 239000012043 crude product Substances 0.000 claims abstract description 8
- 238000001914 filtration Methods 0.000 claims abstract description 7
- 239000002994 raw material Substances 0.000 claims abstract description 7
- 239000003054 catalyst Substances 0.000 claims abstract description 6
- 230000009471 action Effects 0.000 claims abstract description 4
- 239000012141 concentrate Substances 0.000 claims abstract description 4
- 238000010438 heat treatment Methods 0.000 claims abstract description 4
- 230000004044 response Effects 0.000 claims abstract description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 30
- LNURMIDMOXCNEH-UHFFFAOYSA-N 3-bromo-2-chlorobenzoic acid Chemical class OC(=O)C1=CC=CC(Br)=C1Cl LNURMIDMOXCNEH-UHFFFAOYSA-N 0.000 claims description 24
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 16
- 235000019260 propionic acid Nutrition 0.000 claims description 8
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 8
- 230000035484 reaction time Effects 0.000 claims description 7
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 6
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 3
- 235000019253 formic acid Nutrition 0.000 claims description 3
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 3
- FEONEKOZSGPOFN-UHFFFAOYSA-K tribromoiron Chemical compound Br[Fe](Br)Br FEONEKOZSGPOFN-UHFFFAOYSA-K 0.000 abstract description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 abstract description 5
- 239000002253 acid Substances 0.000 abstract description 5
- 230000007613 environmental effect Effects 0.000 abstract description 4
- 239000002351 wastewater Substances 0.000 abstract description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 abstract description 2
- 239000000460 chlorine Substances 0.000 abstract description 2
- 229910052801 chlorine Inorganic materials 0.000 abstract description 2
- FBAFATDZDUQKNH-UHFFFAOYSA-M iron chloride Chemical compound [Cl-].[Fe] FBAFATDZDUQKNH-UHFFFAOYSA-M 0.000 abstract description 2
- 150000003839 salts Chemical class 0.000 abstract description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 abstract 1
- SEBXUZHWZYQTBD-UHFFFAOYSA-N ClC(C1=CC=CC=C1)(Cl)Cl.[Br] Chemical compound ClC(C1=CC=CC=C1)(Cl)Cl.[Br] SEBXUZHWZYQTBD-UHFFFAOYSA-N 0.000 abstract 1
- 239000007787 solid Substances 0.000 description 7
- 239000002904 solvent Substances 0.000 description 5
- 230000008901 benefit Effects 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical class ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 3
- 238000013019 agitation Methods 0.000 description 3
- 150000001335 aliphatic alkanes Chemical class 0.000 description 3
- 238000005352 clarification Methods 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000012065 filter cake Substances 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 238000010792 warming Methods 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- JVHXJTBJCFBINQ-ADAARDCZSA-N Dapagliflozin Chemical compound C1=CC(OCC)=CC=C1CC1=CC([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)=CC=C1Cl JVHXJTBJCFBINQ-ADAARDCZSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 2
- 229910021575 Iron(II) bromide Inorganic materials 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 229960003834 dapagliflozin Drugs 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 2
- GYCHYNMREWYSKH-UHFFFAOYSA-L iron(ii) bromide Chemical compound [Fe+2].[Br-].[Br-] GYCHYNMREWYSKH-UHFFFAOYSA-L 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 239000002910 solid waste Substances 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- MBMLMWLHJBBADN-UHFFFAOYSA-N Ferrous sulfide Chemical compound [Fe]=S MBMLMWLHJBBADN-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000003178 anti-diabetic effect Effects 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 229940046149 ferrous bromide Drugs 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- KAEAMHPPLLJBKF-UHFFFAOYSA-N iron(3+) sulfide Chemical group [S-2].[S-2].[S-2].[Fe+3].[Fe+3] KAEAMHPPLLJBKF-UHFFFAOYSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 238000011020 pilot scale process Methods 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- 238000007867 post-reaction treatment Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000011833 salt mixture Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Classifications
-
- 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
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| 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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| 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 |
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| 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 |
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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 |
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