CN108530263A - A kind of separation and concentration Z-type and the chloro- 2- of E types 3-（4- fluorophenyls）-1-（2- chlorphenyls）The method of propylene - Google Patents
A kind of separation and concentration Z-type and the chloro- 2- of E types 3-（4- fluorophenyls）-1-（2- chlorphenyls）The method of propylene Download PDFInfo
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- CN108530263A CN108530263A CN201810478790.2A CN201810478790A CN108530263A CN 108530263 A CN108530263 A CN 108530263A CN 201810478790 A CN201810478790 A CN 201810478790A CN 108530263 A CN108530263 A CN 108530263A
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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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- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/09—Geometrical isomers
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Abstract
The invention discloses 3 chlorine 2 of a kind of separation and concentration Z-type and E types（4 fluorophenyls）‑1‑（2 chlorphenyls）The method of propylene, includes the following steps：（1）It will be enriched in 3 chlorine 2 of Z-type and E types（4 fluorophenyls）‑1‑（2 chlorphenyls）The mixed liquor of propylene and organic solvent by volume 1：1 ~ 7.5 mixing makes the mixed liquor be dissolved completely in the organic solvent, obtains the first solution；（2）Container equipped with the first solution is placed on cryogenic freezing under 70 ~ 90 DEG C of environment；（3）In step（2）After lamination occurs in solution, supernatant liquor is taken out in separation, obtains E type solution；（4）In step（3）The remaining lower layer's substance of middle separation freezes to be melted after solid, to place it in 20 ~ 30 DEG C of low temperature；（5）Wait for step（4）In solid melt after, take out melting liquid, obtain Z-type solution.The present invention is a kind of pure physics freezing separation method, and obtained product purity is high, and no chemical modification variation, properties of product are stablized, and improve product quality and yield stability.
Description
Technical field
The invention belongs to epoxiconazole production technical fields, and in particular to a kind of separation and concentration Z-type and the chloro- 2- (4- of E types 3-
Fluorophenyl) -1- (2- chlorphenyls) propylene method.
Background technology
Epoxiconazole (Epoxiconazole) trade name Europe is fought, and is a kind of triazole type sterilization of novel, wide spectrum, lasting period length
Agent is developed nineteen eighty-three by BASF Aktiengesellschaft.This product is triazole bactericidal agent, to the damping-offs of cereal crops a series of,
Ten multiple diseases such as powdery mildew, eyeprint disease have good preventive and therapeutic effect, and can prevent sugar beet, peanut, rape, lawn,
The diseases such as coffee, rice and fruit tree；Not only have and protect, treat and root out activity well, but also with interior suction and preferably
Residual activity.Epoxiconazole missible oil production method is as follows：Using fluorobenzene, adjacent chlorobenzyl chloride as starting material, the chloro- 1- (2- of the bromo- 3- of 1- are synthesized
Chlorphenyl) -2- (4- fluorophenyls) -2- propyl alcohol, then reacted through dehydration of alcohols and generate (Z) -3- chloro- 2- (4- fluorophenyls) -1- (2- chlorine
Phenyl) propylene, then passes through N- bromosuccinimide (NBS) bromination, then epoxidation, is finally condensed with 1H-1,2,4- triazoles
Obtain final product；Or (Z) -3- chloro- 2- (4- fluorophenyls) -1- (2- chlorphenyls) propylene pass through NBS brominations, then with 1H-1,2,
4- triazoles are condensed, and last epoxidation obtains final product.
Z-type and the chloro- 2- of E types 3- (4- fluorophenyls) -1- (2- chlorphenyls) propylene are as the important of development epoxiconazole fungicide
Intermediate is having two kinds of structures of Z-type isomers (40-50%) and E-isomer (50-60%) after chloropharin dehydration,
From an economic point of view, it is desirable to which E types are converted into Z-type.The configuration conversion of isomers is a chemical dynamics equilibrium process, this process
It generally can be divided into three types：(1) photoisomerization, the conversion ratio that E types are converted into Z-type is low, in 20%-50% or so；(2)
Thermotropic isomerization, in general, Z type isomers interior energies are relatively high, show that their thermal stability is relatively low, often Z-type isomery
Body is changed into E-isomer by heating；(3) isoversion, it is using the iodine of trace as reaction reagent, Z-type compound is complete
It is converted into its E-isomer entirely.
The above method all has that technical merit is low, can not produce (Z) -3- chloro- 2- (4- fluorophenyls) -1- (2- of high-purity
Chlorphenyl) propylene, and production cost is high, and the chemically modified variation of product or directly becomes (Z) -3- chloro- 2- (4- fluorobenzene
Base) -1- (2- chlorphenyls) propylene will appear the unstable defect of performance.
Invention content
For the deficiency of existing issue, the object of the present invention is to provide a kind of separation and concentration Z-types and the chloro- 2- (4- of E types 3-
Fluorophenyl) -1- (2- chlorphenyls) propylene method, this method is a kind of physics freezing separation method, and obtained product purity is high,
No chemical modification variation, properties of product are stablized.
The present invention solve its technical problem the technical solution adopted is that：
A kind of method of separation and concentration Z-type and the chloro- 2- of E types 3- (4- fluorophenyls) -1- (2- chlorphenyls) propylene, including it is following
Step：
(1) mixed liquor and organic solvent of Z-type and the chloro- 2- of E types 3- (4- fluorophenyls) -1- (2- chlorphenyls) propylene be will be enriched in
By volume 1：1~7.5 mixing makes the mixed liquor be dissolved completely in the organic solvent, obtains the first solution；
(2) container equipped with the first solution is placed on cryogenic freezing under -70~-90 DEG C of environment；
(3) after lamination occurs in the solution of step (2), supernatant liquor is taken out in separation, obtains the second solution；
(4) the remaining lower layer's substance of separation freezes after solid, to place it in -20~-30 DEG C of low temperature and melting in step (3)
Change；
(5) after the solid in step (4) melts, melting liquid is taken out, third solution is obtained.
As the optimal technical scheme of the application, organic solvent is hexane or pentane in the step (1).
As the optimal technical scheme of the application, the step (1) is rich in Z-type and the chloro- 2- of E types 3- (4- fluorophenyls) -1-
The mixed liquor of (2- chlorphenyls) propylene and the volume ratio of organic solvent are 1：1.
As the optimal technical scheme of the application, the temperature of cryogenic freezing is -80 DEG C in the step (2).
It is described to be rich in Z-type and the chloro- 2- of E types 3- (4- fluorophenyls) -1- (2- chlorobenzenes as the optimal technical scheme of the application
Base) propylene mixed liquor first through revolving processing removal of impurities.
The principle of the present invention is with Z-type and the chloro- 2- of E types 3- (4- fluorophenyls) -1- (2- chlorphenyls) propylene in not homopolarity
Property, different volumes than solvent in solubility difference, utilize physics freezing separation method so that E-isomer and Z-type isomery
There is significant change in -70~-90 DEG C of ratios for being distributed in levels because of the difference of solubility in body；This is that a kind of pure physics is cold
Freeze isolation technics, solves separation and concentration Z types and the chloro- 2- of E types 3- (4- fluorophenyls) -1- (2- chlorphenyls) third from mixed liquor
The problem of alkene, obtained Z-type and the chloro- 2- of E types 3- (4- fluorophenyls) -1- (2- chlorphenyls) propylene performance are stablized.
Compared with prior art, method provided by the invention, has the advantages that：
(1) cycle time is produced and processed, entire production process only needs 4-6h, improves production and processing speed, it can be achieved that even
Continuous property production changes solvent strength by solvent dissolving, freezing separation, improves the ratio of E type Z-type isomers；
(2) method of the invention is a kind of pure physics freezing separation technology, and in the second obtained solution, E-isomer accounts for
72% or so, E-isomer is changed into Z-type isomers, improves Z-type isomers by the method that can be converted by isomers
Yield；Z-type isomers accounts for 60% or so in third solution, can be used for the further synthesis of fungicide epoxiconazole.The technique can
Improve Z-type 3- chloro- 2- (4- fluorophenyls) -1- (2- chlorphenyls) utilization rates of propylene and the yield of epoxiconazole；Product purity is higher,
No chemicals residual and Z-type and the chloro- 2- of E types 3- (4- fluorophenyls) -1- (2- chlorphenyls) propylene will not occur chemical change to
The performance of product is stablized, the stability which can improve product quality and yield.
Description of the drawings
Fig. 1 is the process flow chart of embodiment 1 and embodiment 2.
Specific implementation mode
The present invention is described in further details with reference to embodiments.Production is not specified in agents useful for same or instrument and equipment
Manufacturer, it is accordingly to be regarded as the conventional products that can be bought by market.
Fig. 1 is the process flow chart of embodiment 1 and embodiment 2, and specific preparation process is as follows：
Embodiment 1：
1. will be enriched in Z-type and the chloro- 2- of E types 3- (4- fluorophenyls) -1- (2- chlorphenyls) propylene mixed liquor respectively 50 DEG C,
It is rotated at 80 DEG C, removes methanol and toluene；
2. taking the beaker (number of four clean drieds：Hexane 1, hexane 2, hexane 3, hexane 4), it is added in each beaker
Then the hexane of 15mL is added dropwise the above-mentioned revolving liquid of 2mL, 5mL, 10mL and 15mL, obtains the first solution successively；
It is freezed 3. solution is placed in -80 DEG C of refrigerators；
4. occurring lamination after about 4-6h, upper layer is colourless transparent liquid, detaches supernatant liquid under low temperature, obtains second
HPLC is surveyed in solution, sampling, and number is on hexane 1-, on hexane 2-, on hexane 3-, on hexane 4- respectively；
5. lower layer is dark brown solid, it is placed in -30 DEG C of refrigerators, there is thawing phenomenon after about 6min, obtain third solution, take
Sample surveys HPLC, and number is under hexane 1-, under hexane 2-, under hexane 3-, under hexane 4- respectively.
6. being made into test solution after step (4) step (5) sample is diluted, high performance liquid chromatograph, sample introduction body are injected
Product 20-40uL, utilizes UV detector, Detection wavelength 254nm, acetonitrile：Water=3：1 (volume ratio) is used as mobile phase, mobile phase
Flow velocity 1mL/min, using stationary phase octadecyl silane chromatographic column, 40 DEG C of column temperature, to contained Z-type in second and third solution,
The content of the chloro- 2- of E types 3- (4- fluorophenyls) -1- (2- chlorphenyls) propylene is measured.
ZE type ratios in 1 HPLC-100 liquid chromatograies of table
| Substance | Z：E (concentration ratio) | As a result |
| Rotate liquid | 26.377：30.458 | 0.867 |
| On hexane 1- | 24.038：28.414 | 0.846 |
| On hexane 2- | 27.101：33.376 | 0.812 |
| On hexane 3- | 29.743：38.468 | 0.773 |
| On hexane 4- | 22.143：49.558 | 0.447 |
| Under hexane 1- | 30.848：24.003 | 1.282 |
| Under hexane 2- | 37.409：28.877 | 1.295 |
| Under hexane 3- | 39.468：30.316 | 1.302 |
| Under hexane 4- | 38.181：28.302 | 1.349 |
As seen from the above table, it is accumulated with Z-type and the chloro- 2- of E types 3- (4- fluorophenyls) -1- (2- chlorphenyls) propylene revolving liquid
Increase, E types content is gradually increasing in beaker upper liquid, and E-isomer accounts for 69.11% in hexane 4- upper liquids；Under beaker
Layer liquid Z-type content gradually increases, and Z-type isomers accounts for 57.42% in hexane 4- subnatants.
Embodiment 2：
1. will be enriched in Z-type and the chloro- 2- of E types 3- (4- fluorophenyls) -1- (2- chlorphenyls) propylene mixed liquor respectively 50 DEG C, 80
It is rotated at DEG C, removes methanol and toluene；
2. taking the beaker (number of four clean drieds：Pentane 1, pentane 2, pentane 3, pentane 4), each beaker
In the pentane of 15mL is added, the above-mentioned revolving liquid of 2mL, 5mL, 10mL and 15mL are then added dropwise successively, it is molten to obtain first
Liquid；
It is freezed 3. solution is placed in -80 DEG C of refrigerators；
4. occurring lamination after about 4-6h, upper layer is colourless transparent liquid, detaches supernatant liquid under low temperature, obtains second
HPLC is surveyed in solution, sampling, and number is on pentane 1-, on pentane 2-, on pentane 3-, on pentane 4- respectively；
5. lower layer is dark brown solid, it is placed in -30 DEG C of refrigerators, there is thawing phenomenon after about 2min, obtain third solution, take
Sample surveys HPLC, and number is under pentane 1-, under pentane 2-, under pentane 3-, under pentane 4- respectively.
6. being made into test solution after step (4) step (5) sample is diluted, high performance liquid chromatograph, sample introduction body are injected
Product 20-40uL, utilizes UV detector, Detection wavelength 254nm, acetonitrile：Water=3：1 (volume ratio) is used as mobile phase, mobile phase
Flow velocity 1mL/min, using stationary phase octadecyl silane chromatographic column, 40 DEG C of column temperature, to contained Z-type in second and third solution,
The content of the chloro- 2- of E types 3- (4- fluorophenyls) -1- (2- chlorphenyls) propylene is measured.
ZE type ratios in 2 HPLC-100 liquid chromatograies of table
| Substance | Z：E (the ratio between concentration) | As a result |
| Rotate liquid | 26.377：30.458 | 0.866 |
| On pentane 1- | 26.059：30.660 | 0.851 |
| On pentane 2- | 27.861：39.157 | 0.712 |
| On pentane 3- | 27.872：40.700 | 0.611 |
| On pentane 4- | 19.329：49.260 | 0.392 |
| Under pentane 1- | 33.0934：26.6999 | 1.239 |
| Under pentane 2- | 36.120：28.524 | 1.266 |
| Under pentane 3- | 38.044：28.777 | 1.322 |
| Under pentane 4- | 36.8：24.2 | 1.521 |
As seen from the above table, it is accumulated with Z-type and the chloro- 2- of E types 3- (4- fluorophenyls) -1- (2- chlorphenyls) propylene revolving liquid
Increase, E types content is gradually increasing in beaker upper liquid, and E type isomers accounts for 71.82% in pentane 4- upper liquids；Beaker
Subnatant Z-type content gradually increases, and Z-type isomers accounts for 60.33% in pentane 4- subnatants.
The protection content of the present invention is not limited to above example.Without departing from the spirit and scope of the invention, originally
Field technology personnel it is conceivable that variation and advantage be all included in the present invention, and with the attached claims be protection
Range.
Claims (5)
1. a kind of separation and concentration Z-type and the chloro- 2- of E types 3-（4- fluorophenyls）-1-（2- chlorphenyls）The method of propylene, feature exist
In including the following steps：
（1）It will be enriched in Z-type and the chloro- 2- of E types 3-（4- fluorophenyls）-1-（2- chlorphenyls）The mixed liquor of propylene presses body with organic solvent
Product ratio 1：1 ~ 7.5 mixing makes the mixed liquor be dissolved completely in the organic solvent, obtains the first solution；
（2）Container equipped with the first solution is placed on cryogenic freezing under -70 ~ -90 DEG C of environment；
（3）In step（2）Solution there is lamination after, separation take out supernatant liquor, obtain the second solution；
（4）In step（3）The remaining lower layer's substance of middle separation freezes to be melted after solid, to place it in -20 ~ -30 DEG C of low temperature；
（5）Wait for step（4）In solid melt after, take out melting liquid, obtain third solution.
2. separation and concentration Z-type according to claim 1 and the chloro- 2- of E types 3-（4- fluorophenyls）-1-（2- chlorphenyls）Propylene
Method, which is characterized in that the step（1）Middle organic solvent is hexane or pentane.
3. separation and concentration Z-type according to claim 1 and the chloro- 2- of E types 3-（4- fluorophenyls）-1-（2- chlorphenyls）Propylene
Method, which is characterized in that the step（1）Rich in Z-type and the chloro- 2- of E types 3-（4- fluorophenyls）-1-（2- chlorphenyls）Propylene
The volume ratio of mixed liquor and organic solvent is 1：1.
4. separation and concentration Z-type according to claim 1 and the chloro- 2- of E types 3-（4- fluorophenyls）-1-（2- chlorphenyls）Propylene
Method, which is characterized in that the step（2）The temperature of middle cryogenic freezing is -80 DEG C.
5. separation and concentration Z-type according to claim 1 and the chloro- 2- of E types 3-（4- fluorophenyls）-1-（2- chlorphenyls）Propylene
Method, which is characterized in that described to be rich in Z-type and the chloro- 2- of E types 3-（4- fluorophenyls）-1-（2- chlorphenyls）The mixed liquor of propylene is first
Through revolving processing removal of impurities.
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| CN201810478790.2A CN108530263A (en) | 2018-05-18 | 2018-05-18 | A kind of separation and concentration Z-type and the chloro- 2- of E types 3-（4- fluorophenyls）-1-（2- chlorphenyls）The method of propylene |
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| CN201810478790.2A CN108530263A (en) | 2018-05-18 | 2018-05-18 | A kind of separation and concentration Z-type and the chloro- 2- of E types 3-（4- fluorophenyls）-1-（2- chlorphenyls）The method of propylene |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5268517A (en) * | 1989-07-14 | 1993-12-07 | Basf Aktiengesellschaft | Stereoselective preparation of Z-1,2-diarylallyl chlorides and the conversion thereof into azolylmethyloxiranes, and novel intermediates |
| CN101928236A (en) * | 2009-11-05 | 2010-12-29 | 甘肃银达化工有限公司 | Method for separating TDI monomer with different isomerization rates |
| CN103936552A (en) * | 2013-01-23 | 2014-07-23 | 中国中化股份有限公司 | Preparation method of epoxiconazole intermediate (Z)-2-(4-fluorophenyl)-1-(2-chlorphenyl)-3-halogen propylene |
-
2018
- 2018-05-18 CN CN201810478790.2A patent/CN108530263A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5268517A (en) * | 1989-07-14 | 1993-12-07 | Basf Aktiengesellschaft | Stereoselective preparation of Z-1,2-diarylallyl chlorides and the conversion thereof into azolylmethyloxiranes, and novel intermediates |
| CN101928236A (en) * | 2009-11-05 | 2010-12-29 | 甘肃银达化工有限公司 | Method for separating TDI monomer with different isomerization rates |
| CN103936552A (en) * | 2013-01-23 | 2014-07-23 | 中国中化股份有限公司 | Preparation method of epoxiconazole intermediate (Z)-2-(4-fluorophenyl)-1-(2-chlorphenyl)-3-halogen propylene |
Non-Patent Citations (1)
| Title |
|---|
| 衣丹等: ":共轭亚油酸两种主要异构体冷冻结晶分离工艺研究", 《食品与机械》 * |
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