CN105884587B - A method of synthesis chloromethyl -1,1,1,3,3,3- hexafluoroisopropyl ethers - Google Patents
A method of synthesis chloromethyl -1,1,1,3,3,3- hexafluoroisopropyl ethers Download PDFInfo
- Publication number
- CN105884587B CN105884587B CN201610265168.4A CN201610265168A CN105884587B CN 105884587 B CN105884587 B CN 105884587B CN 201610265168 A CN201610265168 A CN 201610265168A CN 105884587 B CN105884587 B CN 105884587B
- Authority
- CN
- China
- Prior art keywords
- autoclave
- carbon dioxide
- chloromethyl
- synthesis
- isopropyl ether
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 46
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 46
- 238000000034 method Methods 0.000 title claims abstract description 34
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 title claims description 23
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims abstract description 95
- 238000006243 chemical reaction Methods 0.000 claims abstract description 51
- 229910002092 carbon dioxide Inorganic materials 0.000 claims abstract description 47
- 239000001569 carbon dioxide Substances 0.000 claims abstract description 47
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 24
- HHYFUCXZHKDNPT-UHFFFAOYSA-N 2-(chloromethoxy)-1,1,1,3,3,3-hexafluoropropane Chemical compound FC(F)(F)C(C(F)(F)F)OCCl HHYFUCXZHKDNPT-UHFFFAOYSA-N 0.000 claims abstract description 22
- 239000012044 organic layer Substances 0.000 claims abstract description 20
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 claims abstract description 19
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims abstract description 15
- 238000003756 stirring Methods 0.000 claims abstract description 15
- 239000007788 liquid Substances 0.000 claims abstract description 14
- 229920002866 paraformaldehyde Polymers 0.000 claims abstract description 14
- 238000009423 ventilation Methods 0.000 claims abstract description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 10
- 229930040373 Paraformaldehyde Natural products 0.000 claims abstract description 7
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 27
- 229910002090 carbon oxide Inorganic materials 0.000 claims 1
- 239000002904 solvent Substances 0.000 abstract description 8
- 230000008569 process Effects 0.000 abstract description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 28
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 17
- 239000000047 product Substances 0.000 description 17
- 230000006837 decompression Effects 0.000 description 9
- DFEYYRMXOJXZRJ-UHFFFAOYSA-N sevoflurane Chemical compound FCOC(C(F)(F)F)C(F)(F)F DFEYYRMXOJXZRJ-UHFFFAOYSA-N 0.000 description 9
- 229960002078 sevoflurane Drugs 0.000 description 9
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 7
- 238000005160 1H NMR spectroscopy Methods 0.000 description 7
- 238000005481 NMR spectroscopy Methods 0.000 description 7
- 238000009835 boiling Methods 0.000 description 7
- 238000004587 chromatography analysis Methods 0.000 description 7
- 239000008213 purified water Substances 0.000 description 7
- 239000012535 impurity Substances 0.000 description 4
- 230000008859 change Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- BGJSXRVXTHVRSN-UHFFFAOYSA-N 1,3,5-trioxane Chemical compound C1OCOCO1 BGJSXRVXTHVRSN-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- CXJWJJZGJZNBRK-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoro-2-(1,1,1,3,3,3-hexafluoropropan-2-yloxy)propane Chemical compound FC(F)(F)C(C(F)(F)F)OC(C(F)(F)F)C(F)(F)F CXJWJJZGJZNBRK-UHFFFAOYSA-N 0.000 description 1
- 150000004904 1,3,5-trioxanes Chemical class 0.000 description 1
- ZRNSSRODJSSVEJ-UHFFFAOYSA-N 2-methylpentacosane Chemical compound CCCCCCCCCCCCCCCCCCCCCCCC(C)C ZRNSSRODJSSVEJ-UHFFFAOYSA-N 0.000 description 1
- OOKYWAXNZYBZER-UHFFFAOYSA-N 3-amino-3-(4-ethoxy-3-methoxyphenyl)propanoic acid Chemical compound CCOC1=CC=C(C(N)CC(O)=O)C=C1OC OOKYWAXNZYBZER-UHFFFAOYSA-N 0.000 description 1
- QGHDLJAZIIFENW-UHFFFAOYSA-N 4-[1,1,1,3,3,3-hexafluoro-2-(4-hydroxy-3-prop-2-enylphenyl)propan-2-yl]-2-prop-2-enylphenol Chemical group C1=C(CC=C)C(O)=CC=C1C(C(F)(F)F)(C(F)(F)F)C1=CC=C(O)C(CC=C)=C1 QGHDLJAZIIFENW-UHFFFAOYSA-N 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- XYQSAJYDJWAKKT-UHFFFAOYSA-N C(C)(C)O.[F] Chemical compound C(C)(C)O.[F] XYQSAJYDJWAKKT-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000012320 chlorinating reagent Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- POLCUAVZOMRGSN-UHFFFAOYSA-N dipropyl ether Chemical compound CCCOCCC POLCUAVZOMRGSN-UHFFFAOYSA-N 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 230000000004 hemodynamic effect Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000003983 inhalation anesthetic agent Substances 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229910001512 metal fluoride Inorganic materials 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- NBVXSUQYWXRMNV-UHFFFAOYSA-N monofluoromethane Natural products FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/54—Improvements relating to the production of bulk chemicals using solvents, e.g. supercritical solvents or ionic liquids
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a kind of method of synthesis chloromethyl-1,1,1,3,3,3-hexafluoro isopropyl ether, this method includes：One, hexafluoroisopropanol and paraformaldehyde are added into autoclave, aluminum trichloride (anhydrous) is added into the autoclave after stirring evenly, it is 0 DEG C~50 DEG C to control the temperature in autoclave, then pass to carbon dioxide gas, insulated and stirred is reacted after ventilation, and the intake of carbon dioxide gas is that carbon dioxide is made to be in a liquid state or above-critical state；Two, reaction mass dissolving with hydrochloric acid is separated organic layer by discharge carbon dioxide, and organic layer is washed with water, obtains chloromethyl-1,1,1,3,3,3-hexafluoro isopropyl ether.The present invention is conducive to stir using liquid or the supercritical carbon dioxide as solvent, keeps the comparison that reaction carries out complete, and is easy to detach with product, eliminates complicated last handling process, product yield reaches 90% or more, and purity reaches 98% or more.
Description
Technical field
The invention belongs to chemosynthesis technical fields, and in particular to a kind of synthesis chloromethyl -1,1,1,3,3,3- hexafluoro are different
The method of propyl ether.
Background technology
Sevoflurane (methyl fluoride -1,1,1,3,3,3- hexafluoroisopropyl ether) is a kind of inhalation anesthetic, because it has induction
Phase is short, recovery is fast, be easily metabolized, blood & air partition coefficent is low, hemodynamic stability, small to human body adverse reaction, depth of anesthesia is easy
The advantages that adjusting and is nonflammable explosive, is widely paid close attention to and is paid attention in the world.And chloromethyl -1,1,1,3,3,3- hexafluoros
Isopropyl ether is the important intermediate for synthesizing fluoromethyl-1,1,1,3,3,3-hexafluoroisopropylether.United States Patent (USP) 6100434 is reported
The use of hexafluoroisopropanol is raw material, generate the aluminum trichloride (anhydrous) and metaformaldehyde in the presence of intermediate (chloromethyl -1,1,1,
3,3,3- hexafluoroisopropyl ethers), intermediate reacts the method for preparing sevoflurane with metal fluoride.But there are following technologies for the method
Problem：(1) first step reaction process is phase reaction, and reaction process is easy solidification, it is extremely difficult to stir, to make reaction mass can not
It is uniformly mixed, reaction is difficult to carry out thoroughly；(2) sevoflurane intermediate purity formed by the first reaction is not high, and impurity is more, receives
Rate is relatively low.Patent WO2008037039 is described using hexafluoroisopropanol as raw material and metaformaldehyde equivalent, strong acid and chlorination
The method that sevoflurane intermediate prepares sevoflurane that generates directly is reacted in agent.The method is primarily present following technical barrier：(1) hexafluoro is different
Propyl alcohol conversion ratio is relatively low, to increase manufacturing cost；(2) impurity in sevoflurane intermediate is more, it is difficult to purify, finally lead
Cause sevoflurane impurity more.Patent WO201009695 is described in the case where appropriate chloro-carbon solvent is added, with anhydrous chlorine
Change lewis acid is catalyst, and by hexafluoroisopropanol and 1,3,5- trioxanes or paraformaldehyde reaction generate chloromethyl-
1,1,1,3,3,3- hexafluoroisopropyl ether, although which solves stirring difficulty and reaction mass is uniformly mixed this problem, but
Since organic solvent is added, and the new problem for bringing solvent to detach, cause intermediate separating-purifying difficult, simultaneously as molten containing chlorine
The addition of agent easily introduces new impurity in halogenated exchange reaction, to seriously affect the purity of finished product sevoflurane.
Therefore, it explores that a kind of reaction condition is mild, easy to operate, cost is relatively low, separating-purifying is easy, and height can be obtained
The novel synthesis of purity chloromethyl -1,1,1,3,3,3- hexafluoroisopropyl ethers is necessary.
Invention content
In view of the above-mentioned deficiencies in the prior art, the technical problem to be solved by the present invention is that providing a kind of synthesis chloromethane
The method of base -1,1,1,3,3,3- hexafluoroisopropyl ethers.This method is conducive to using liquid or the supercritical carbon dioxide as solvent
Stirring keeps the comparison that reaction carries out complete, and liquid or supercritical carbon dioxide become gas by decompression and be easy to and produce
Object detaches, and the completely left out complicated last handling process brought with conventional solvent improves the purity and yield of reaction product,
Product yield reaches 90% or more, and purity reaches 98% or more.
In order to solve the above technical problems, the technical solution adopted by the present invention is：A kind of synthesis chloromethyl -1,1,1,3,3,3-
The method of hexafluoroisopropyl ether, which is characterized in that include the following steps：
Step 1: hexafluoroisopropanol and paraformaldehyde are added into autoclave, it is anti-to the high pressure after stirring evenly
It answers and aluminum trichloride (anhydrous) is added in kettle, it is 0 DEG C~50 DEG C to control the temperature in autoclave, is then led into autoclave
Enter carbon dioxide gas, insulated and stirred reacts 5h~7h after ventilation；The intake of the carbon dioxide gas is to make high pressure
Carbon dioxide in reaction kettle is in a liquid state or above-critical state；
Step 2: waiting for that the carbon dioxide in autoclave is discharged in insulated and stirred after reaction in step 1, by high pressure
Reaction mass dissolving with hydrochloric acid in reaction kettle, then separates organic layer, and the organic layer separated is washed with water, obtains chloromethyl-
1,1,1,3,3,3- hexafluoroisopropyl ethers.
A kind of method of above-mentioned synthesis chloromethyl-1,1,1,3,3,3-hexafluoro isopropyl ether, which is characterized in that step 1
The molar ratio of formaldehyde is (0.8~1) in middle hexafluoroisopropanol and paraformaldehyde:1.
A kind of method of above-mentioned synthesis chloromethyl-1,1,1,3,3,3-hexafluoro isopropyl ether, which is characterized in that step 1
The molar ratio of middle hexafluoroisopropanol and aluminum trichloride (anhydrous) is 1:(1~2).
The method of above-mentioned a kind of synthesis chloromethyl-1,1,1,3,3,3-hexafluoro isopropyl ether, which is characterized in that described six
The molar ratio of fluorine isopropanol and aluminum trichloride (anhydrous) is 1:(1.2~1.5).
A kind of method of above-mentioned synthesis chloromethyl-1,1,1,3,3,3-hexafluoro isopropyl ether, which is characterized in that step 1
Temperature in middle control autoclave is 15 DEG C~35 DEG C.
A kind of method of above-mentioned synthesis chloromethyl-1,1,1,3,3,3-hexafluoro isopropyl ether, which is characterized in that step 1
Described in insulated and stirred reaction temperature be 0 DEG C~50 DEG C.
A kind of method of above-mentioned synthesis chloromethyl-1,1,1,3,3,3-hexafluoro isopropyl ether, which is characterized in that step 2
Described in hydrochloric acid a concentration of 4mol/L~8mol/L.
Compared with the prior art, the present invention has the following advantages：
1, the present invention is by controlling the temperature in autoclave, and is passed through carbon dioxide to certain pressure so that high pressure
Carbon dioxide in reaction kettle exists with liquid or above-critical state, using liquid or the supercritical carbon dioxide as solvent, with anhydrous
Alchlor is catalyst and chlorinating agent, and hexafluoroisopropanol and paraformaldehyde, which react, generates chloromethyl -1,1,1,3,3,3-
Hexafluoroisopropyl ether, improves original technique, reaction process is simple, it is easy to operate, economic and practical, meet environmental requirement, and
Sevoflurane intermediate chloromethyl -1,1, the yield and purity of 1,3,3,3- hexafluoroisopropyl ether are greatly improved, yield reaches
90% or more, purity reaches 98% or more.
2, the present invention is conducive to stir using liquid or the supercritical carbon dioxide as solvent, so that reaction is carried out completeer
Entirely, and liquid or supercritical carbon dioxide become gas by decompression and are easy to detach with product, completely left out with traditional
The complicated last handling process that solvent bank comes, improves the purity and yield of reaction product.
Below by embodiment, technical scheme of the present invention will be described in further detail.
Specific implementation mode
Embodiment 1
The method of the present embodiment synthesis chloromethyl -1,1,1,3,3,3- hexafluoroisopropyl ethers includes the following steps：
Step 1: 168.0g (1.0mol) hexafluoroisopropanols and 30.0g paraformaldehydes are added into autoclave (quite
In 1.0mol formaldehyde), 160.0g (1.2mol) aluminum trichloride (anhydrous), control is added after stirring evenly into the autoclave
Temperature in autoclave is 34 DEG C, the pressure being then passed through into autoclave in carbon dioxide gas to autoclave
Power is 8.0MPa~8.5MPa, and the carbon dioxide in autoclave is in above-critical state at this time, 32 DEG C~36 after ventilation
DEG C insulated and stirred reacts 6h；
Step 2: waiting for that insulated and stirred makes carbon dioxide be in gas shape autoclave decompression after reaction in step 1
The carbon dioxide gas in autoclave is discharged, by the 6mol/L dissolving with hydrochloric acid of the reaction mass in autoclave, so in state
Dissolved reaction mass is poured into separatory funnel afterwards, organic layer is separated after standing 40min, is washed repeatedly with purified water organic
Layer 6 times, obtains 200.8g chloromethyl-1,1,1,3,3,3-hexafluoro isopropyl ethers, yield 92.7%.
The product of the present embodiment synthesis is detected, bp=76 DEG C of boiling point, nuclear magnetic resonance spectroscopy result is：1H-NMR
(CDCl3, 400MHz) and δ 5.55 (s, 2H), 4.54 (septet, 1H, JFCCH=5.7Hz)；13C-NMR(CDCl3, 100MHz) and δ
121.3(dq,JFC=283Hz, JFCCC=3.0Hz), 80.2 (s), 73.1 (septet, 1H, JFCC=33.4Hz), illustrate this reality
The product for applying example synthesis is chloromethyl -1,1,1,3,3,3- hexafluoroisopropyl ethers.
Gas chromatographic analysis, chloromethane are carried out to the chloromethyl-1,1,1,3,3,3-hexafluoro isopropyl ether of the present embodiment synthesis
The purity of base -1,1,1,3,3,3- hexafluoroisopropyl ethers is 98.7%.
Embodiment 2
The method of the present embodiment synthesis chloromethyl -1,1,1,3,3,3- hexafluoroisopropyl ethers includes the following steps：
Step 1: 504.0g (3.0mol) hexafluoroisopropanols and 90.0g paraformaldehydes are added into autoclave (quite
In 3.0mol formaldehyde), 600.0g (4.5mol) aluminum trichloride (anhydrous), control is added after stirring evenly into the autoclave
Temperature in autoclave is 35 DEG C, the pressure being then passed through into autoclave in carbon dioxide gas to autoclave
Power is 8.5MPa~9.0MPa, and the carbon dioxide in autoclave is in above-critical state at this time, 33 DEG C~37 after ventilation
DEG C insulated and stirred reacts 5h；
Step 2: waiting for that insulated and stirred makes carbon dioxide be in gas shape autoclave decompression after reaction in step 1
The carbon dioxide gas in autoclave is discharged, by the 4mol/L dissolving with hydrochloric acid of the reaction mass in autoclave, so in state
Dissolved reaction mass is poured into separatory funnel afterwards, organic layer is separated after standing 50min, is washed repeatedly with purified water organic
Layer 6 times, obtains 594.3g chloromethyl-1,1,1,3,3,3-hexafluoro isopropyl ethers, yield 91.5%.
The product of the present embodiment synthesis is detected, bp=76 DEG C of boiling point, nuclear magnetic resonance spectroscopy result is：1H-NMR
(CDCl3, 400MHz) and δ 5.55 (s, 2H), 4.54 (septet, 1H, JFCCH=5.7Hz)；13C-NMR(CDCl3, 100MHz) and δ
121.3(dq,JFC=283Hz, JFCCC=3.0Hz), 80.2 (s), 73.1 (septet, 1H, JFCC=33.4Hz), illustrate this reality
The product for applying example synthesis is chloromethyl -1,1,1,3,3,3- hexafluoroisopropyl ethers.
Gas chromatographic analysis, chloromethane are carried out to the chloromethyl-1,1,1,3,3,3-hexafluoro isopropyl ether of the present embodiment synthesis
The purity of base -1,1,1,3,3,3- hexafluoroisopropyl ethers is 98.5%.
Embodiment 3
The method of the present embodiment synthesis chloromethyl -1,1,1,3,3,3- hexafluoroisopropyl ethers includes the following steps：
Step 1: 168.0g (1.0mol) hexafluoroisopropanols and 30.0g paraformaldehydes are added into autoclave (quite
In 1.0mol formaldehyde), 160.0g (1.2mol) aluminum trichloride (anhydrous), room temperature is added after stirring evenly into the autoclave
The lower pressure being passed through into autoclave in carbon dioxide gas to autoclave is 7.5MPa~8.0MPa, at this time high pressure
Carbon dioxide in reaction kettle is in a liquid state, and reacts 7h in 22 DEG C~25 DEG C insulated and stirreds after ventilation；
Step 2: waiting for that insulated and stirred makes carbon dioxide be in gas shape autoclave decompression after reaction in step 1
The carbon dioxide gas in autoclave is discharged, by the 8mol/L dissolving with hydrochloric acid of the reaction mass in autoclave, so in state
Dissolved reaction mass is poured into separatory funnel afterwards, organic layer is separated after standing 40min, is washed repeatedly with purified water organic
Layer 4 times, obtains 199.2g chloromethyl-1,1,1,3,3,3-hexafluoro isopropyl ethers, yield 92.0%.
The product of the present embodiment synthesis is detected, bp=76 DEG C of boiling point, nuclear magnetic resonance spectroscopy result is：1H-NMR
(CDCl3, 400MHz) and δ 5.55 (s, 2H), 4.54 (septet, 1H, JFCCH=5.7Hz)；13C-NMR(CDCl3, 100MHz) and δ
121.3(dq,JFC=283Hz, JFCCC=3.0Hz), 80.2 (s), 73.1 (septet, 1H, JFCC=33.4Hz), illustrate this reality
The product for applying example synthesis is chloromethyl -1,1,1,3,3,3- hexafluoroisopropyl ethers.
Gas chromatographic analysis, chloromethane are carried out to the chloromethyl-1,1,1,3,3,3-hexafluoro isopropyl ether of the present embodiment synthesis
The purity of base -1,1,1,3,3,3- hexafluoroisopropyl ethers is 98.2%.
Embodiment 4
The method of the present embodiment synthesis chloromethyl -1,1,1,3,3,3- hexafluoroisopropyl ethers includes the following steps：
Step 1: 504.0g (3.0mol) hexafluoroisopropanols and 90.0g paraformaldehydes are added into autoclave (quite
In 3.0mol formaldehyde), 600.0g (4.5mol) aluminum trichloride (anhydrous), room temperature is added after stirring evenly into the autoclave
The lower pressure being passed through into autoclave in carbon dioxide gas to autoclave is 7.0MPa~7.5MPa, at this time high pressure
Carbon dioxide in reaction kettle is in a liquid state, and reacts 6h in 18 DEG C~22 DEG C insulated and stirreds after ventilation；
Step 2: waiting for that insulated and stirred makes carbon dioxide be in gas shape autoclave decompression after reaction in step 1
The carbon dioxide gas in autoclave is discharged, by the 7mol/L dissolving with hydrochloric acid of the reaction mass in autoclave, so in state
Dissolved reaction mass is poured into separatory funnel afterwards, organic layer is separated after standing 60min, is washed repeatedly with purified water organic
Layer 6 times, obtains 600.2g chloromethyl-1,1,1,3,3,3-hexafluoro isopropyl ethers, yield 92.4%.
The product of the present embodiment synthesis is detected, bp=76 DEG C of boiling point, nuclear magnetic resonance spectroscopy result is：1H-NMR
(CDCl3, 400MHz) and δ 5.55 (s, 2H), 4.54 (septet, 1H, JFCCH=5.7Hz)；13C-NMR(CDCl3, 100MHz) and δ
121.3(dq,JFC=283Hz, JFCCC=3.0Hz), 80.2 (s), 73.1 (septet, 1H, JFCC=33.4Hz), illustrate this reality
The product for applying example synthesis is chloromethyl -1,1,1,3,3,3- hexafluoroisopropyl ethers.
Gas chromatographic analysis, chloromethane are carried out to the chloromethyl-1,1,1,3,3,3-hexafluoro isopropyl ether of the present embodiment synthesis
The purity of base -1,1,1,3,3,3- hexafluoroisopropyl ethers is 99.0%.
Embodiment 5
The method of the present embodiment synthesis chloromethyl -1,1,1,3,3,3- hexafluoroisopropyl ethers includes the following steps：
Step 1: 403.2g (2.4mol) hexafluoroisopropanols and 90.0g paraformaldehydes are added into autoclave (quite
In 3.0mol formaldehyde), 640.0g (4.8mol) aluminum trichloride (anhydrous), control is added after stirring evenly into the autoclave
Temperature in autoclave is 0 DEG C, the pressure being then passed through into autoclave in carbon dioxide gas to autoclave
Power is 6.0MPa~6.5MPa, and the carbon dioxide in autoclave is in a liquid state at this time, is kept the temperature at 0 DEG C~2 DEG C after ventilation
It is stirred to react 7h；
Step 2: waiting for that insulated and stirred makes carbon dioxide be in gas shape autoclave decompression after reaction in step 1
The carbon dioxide gas in autoclave is discharged, by the 6mol/L dissolving with hydrochloric acid of the reaction mass in autoclave, so in state
Dissolved reaction mass is poured into separatory funnel afterwards, organic layer is separated after standing 40min, is washed repeatedly with purified water organic
Layer 6 times, obtains 477.0g chloromethyl-1,1,1,3,3,3-hexafluoro isopropyl ethers, yield 91.8%.
The product of the present embodiment synthesis is detected, bp=76 DEG C of boiling point, nuclear magnetic resonance spectroscopy result is：1H-NMR
(CDCl3, 400MHz) and δ 5.55 (s, 2H), 4.54 (septet, 1H, JFCCH=5.7Hz)；13C-NMR(CDCl3, 100MHz) and δ
121.3(dq,JFC=283Hz, JFCCC=3.0Hz), 80.2 (s), 73.1 (septet, 1H, JFCC=33.4Hz), illustrate this reality
The product for applying example synthesis is chloromethyl -1,1,1,3,3,3- hexafluoroisopropyl ethers.
Gas chromatographic analysis, chloromethane are carried out to the chloromethyl-1,1,1,3,3,3-hexafluoro isopropyl ether of the present embodiment synthesis
The purity of base -1,1,1,3,3,3- hexafluoroisopropyl ethers is 98.7%.
Embodiment 6
The method of the present embodiment synthesis chloromethyl -1,1,1,3,3,3- hexafluoroisopropyl ethers includes the following steps：
Step 1: 168.0g (1.0mol) hexafluoroisopropanols and 30.0g paraformaldehydes are added into autoclave (quite
In 1.0mol formaldehyde), 133.3g (1.0mol) aluminum trichloride (anhydrous), control is added after stirring evenly into the autoclave
Temperature in autoclave is 50 DEG C, the pressure being then passed through into autoclave in carbon dioxide gas to autoclave
Power is 9.5MPa~10.0MPa, and the carbon dioxide in autoclave is in above-critical state at this time, 46 DEG C~50 after ventilation
DEG C insulated and stirred reacts 6h；
Step 2: waiting for that insulated and stirred makes carbon dioxide be in gas shape autoclave decompression after reaction in step 1
The carbon dioxide gas in autoclave is discharged, by the 6mol/L dissolving with hydrochloric acid of the reaction mass in autoclave, so in state
Dissolved reaction mass is poured into separatory funnel afterwards, organic layer is separated after standing 50min, is washed repeatedly with purified water organic
Layer 5 times, obtains 200.5g chloromethyl-1,1,1,3,3,3-hexafluoro isopropyl ethers, yield 92.6%.
The product of the present embodiment synthesis is detected, bp=76 DEG C of boiling point, nuclear magnetic resonance spectroscopy result is：1H-NMR
(CDCl3, 400MHz) and δ 5.55 (s, 2H), 4.54 (septet, 1H, JFCCH=5.7Hz)；13C-NMR(CDCl3, 100MHz) and δ
121.3(dq,JFC=283Hz, JFCCC=3.0Hz), 80.2 (s), 73.1 (septet, 1H, JFCC=33.4Hz), illustrate this reality
The product for applying example synthesis is chloromethyl -1,1,1,3,3,3- hexafluoroisopropyl ethers.
Gas chromatographic analysis, chloromethane are carried out to the chloromethyl-1,1,1,3,3,3-hexafluoro isopropyl ether of the present embodiment synthesis
The purity of base -1,1,1,3,3,3- hexafluoroisopropyl ethers is 99.2%.
Embodiment 7
The method of the present embodiment synthesis chloromethyl -1,1,1,3,3,3- hexafluoroisopropyl ethers includes the following steps：
Step 1: 151.2g (0.9mol) hexafluoroisopropanols and 30.0g paraformaldehydes are added into autoclave (quite
In 1.0mol formaldehyde), 160g (1.2mol) aluminum trichloride (anhydrous) is added after stirring evenly into the autoclave, control is high
It is 15 DEG C to press the temperature in reaction kettle, the pressure being then passed through into autoclave in carbon dioxide gas to autoclave
For 6.0MPa~6.5MPa, the carbon dioxide in autoclave is in a liquid state at this time, is kept the temperature at 12 DEG C~16 DEG C after ventilation
It is stirred to react 5h；
Step 2: waiting for that insulated and stirred makes carbon dioxide be in gas shape autoclave decompression after reaction in step 1
The carbon dioxide gas in autoclave is discharged, by the 5mol/L dissolving with hydrochloric acid of the reaction mass in autoclave, so in state
Dissolved reaction mass is poured into separatory funnel afterwards, organic layer is separated after standing 45min, is washed repeatedly with purified water organic
Layer 6 times, obtains 177.1g chloromethyl-1,1,1,3,3,3-hexafluoro isopropyl ethers, yield 90.9%.
The product of the present embodiment synthesis is detected, bp=76 DEG C of boiling point, nuclear magnetic resonance spectroscopy result is：1H-NMR
(CDCl3, 400MHz) and δ 5.55 (s, 2H), 4.54 (septet, 1H, JFCCH=5.7Hz)；13C-NMR(CDCl3, 100MHz) and δ
121.3(dq,JFC=283Hz, JFCCC=3.0Hz), 80.2 (s), 73.1 (septet, 1H, JFCC=33.4Hz), illustrate this reality
The product for applying example synthesis is chloromethyl -1,1,1,3,3,3- hexafluoroisopropyl ethers.
Gas chromatographic analysis, chloromethane are carried out to the chloromethyl-1,1,1,3,3,3-hexafluoro isopropyl ether of the present embodiment synthesis
The purity of base -1,1,1,3,3,3- hexafluoroisopropyl ethers is 98.6%.
The above is only presently preferred embodiments of the present invention, is not imposed any restrictions to the present invention, every according to the present invention
Technical spirit still falls within the technology of the present invention side to any simple modification, change and equivalence change made by above example
In the protection domain of case.
Claims (5)
1. a kind of method of synthesis chloromethyl-1,1,1,3,3,3-hexafluoro isopropyl ether, which is characterized in that include the following steps：
Step 1: hexafluoroisopropanol and paraformaldehyde are added into autoclave, to the autoclave after stirring evenly
Middle addition aluminum trichloride (anhydrous), the temperature controlled in autoclave is 0 DEG C~50 DEG C, and two are then passed through into autoclave
Carbon oxide gas, insulated and stirred reacts 5h~7h after ventilation；The intake of the carbon dioxide gas is to make reaction under high pressure
Carbon dioxide in kettle is in a liquid state or above-critical state；The molar ratio of formaldehyde is (0.8~1) in hexafluoroisopropanol and paraformaldehyde:
1；The molar ratio of hexafluoroisopropanol and aluminum trichloride (anhydrous) is 1:(1~2)；
Step 2: waiting for that the carbon dioxide in autoclave is discharged in insulated and stirred after reaction in step 1, by reaction under high pressure
Reaction mass dissolving with hydrochloric acid in kettle, then separates organic layer, and the organic layer separated is washed with water, obtains chloromethyl -1,1,
1,3,3,3- hexafluoroisopropyl ethers.
2. a kind of method of synthesis chloromethyl-1,1,1,3,3,3-hexafluoro isopropyl ether according to claim 1, feature
It is, the molar ratio of the hexafluoroisopropanol and aluminum trichloride (anhydrous) is 1:(1.2~1.5).
3. a kind of method of synthesis chloromethyl-1,1,1,3,3,3-hexafluoro isopropyl ether according to claim 1, feature
It is, it is 15 DEG C~35 DEG C that the temperature in autoclave is controlled in step 1.
4. a kind of method of synthesis chloromethyl-1,1,1,3,3,3-hexafluoro isopropyl ether according to claim 1, feature
It is, the temperature of the reaction of insulated and stirred described in step 1 is 0 DEG C~50 DEG C.
5. a kind of method of synthesis chloromethyl-1,1,1,3,3,3-hexafluoro isopropyl ether according to claim 1, feature
It is, a concentration of 4mol/L~8mol/L of hydrochloric acid described in step 2.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610265168.4A CN105884587B (en) | 2016-04-26 | 2016-04-26 | A method of synthesis chloromethyl -1,1,1,3,3,3- hexafluoroisopropyl ethers |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610265168.4A CN105884587B (en) | 2016-04-26 | 2016-04-26 | A method of synthesis chloromethyl -1,1,1,3,3,3- hexafluoroisopropyl ethers |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105884587A CN105884587A (en) | 2016-08-24 |
| CN105884587B true CN105884587B (en) | 2018-10-30 |
Family
ID=56704668
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610265168.4A Active CN105884587B (en) | 2016-04-26 | 2016-04-26 | A method of synthesis chloromethyl -1,1,1,3,3,3- hexafluoroisopropyl ethers |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105884587B (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2548548B (en) | 2016-02-23 | 2020-12-09 | Sagetech Medical Equipment Ltd | Improvements in the capture and elution of halocarbons by supercritical fluids |
| GB2547651B (en) * | 2016-02-23 | 2021-02-03 | Sagetech Medical Equipment Ltd | Processes for the preparation of sevoflurane and desflurane |
| GB2587294B (en) * | 2016-02-23 | 2021-06-16 | Sagetech Medical Equipment Ltd | Processes for the preparation of desflurane |
| CN108689808B (en) * | 2017-04-06 | 2021-11-16 | 江苏恒瑞医药股份有限公司 | Preparation method of chloromethyl hexafluoroisopropyl ether |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6426391B1 (en) * | 1999-05-07 | 2002-07-30 | The University Of North Carolina At Chapel Hill | Fluorination in liquid or supercritical carbon dioxide |
| WO2010096959A1 (en) * | 2009-02-25 | 2010-09-02 | 江苏恒瑞医药股份有限公司 | A process for preparing chloromethyl-1,1,1,3,3,3- hexafluoroisopropyl ether |
-
2016
- 2016-04-26 CN CN201610265168.4A patent/CN105884587B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN105884587A (en) | 2016-08-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105884587B (en) | A method of synthesis chloromethyl -1,1,1,3,3,3- hexafluoroisopropyl ethers | |
| CN105693470A (en) | Continuous 3-methyl-3-buten-1-ol production method | |
| CN103254201B (en) | A kind of preparation method of asenapine | |
| CN106188116A (en) | A kind of method of synthesizing pyrazole 4 boric acid pinacol ester | |
| CN101643397B (en) | Preparation method of cyclopropyl methyl ketone and bicyclo-propyl ketone | |
| CN106565475A (en) | Preparing method for ethyl 4,4,4-trifluoroacetoacetate | |
| CN104177260B (en) | A kind of preparation method of conventional auxiliary material | |
| CN103864865A (en) | A synthetic method of high-purity tulathromycin | |
| CN102617622A (en) | Method for preparing moxifloxacin or its medicinal salt and its intermediate | |
| CN106083944B (en) | A kind of preparation method of sucrose fatty ester | |
| CN114163316B (en) | Method for preparing 4-bromo-2-methoxy-5-trifluoromethyl benzaldehyde | |
| CN103739604A (en) | Preparation method of Pralatrexate suitable for industrial large scale production | |
| CN109232201A (en) | A kind of improved sevoflurane reaction solution post-processing approach | |
| CN108218703A (en) | A kind of preparation method of 4,4- difluoros ethyl acetoacetate | |
| CN104592027A (en) | Method for preparing methyl benzoate | |
| CN107935971A (en) | It is a kind of（S）The preparation method of 3 hydroxyl tetrahydrofurans | |
| CN105801482B (en) | A kind of preparation method of the bromo- 8- difluoro-methoxies -1,4- dihydroquinoline -3- carboxylic acid, ethyl esters of 1- cyclopropyl -4- oxos -7- | |
| CN106365972A (en) | 1,1,1-trifluoro-2-butanone preparation method | |
| CN109796317B (en) | Preparation method of 1-phenyl-2-butanone | |
| CN110452198B (en) | Preparation method of feloxicib | |
| CN108084023A (en) | A kind of preparation method of 1- chloroethenes yl acetate | |
| CN103044362A (en) | Method for preparing hexafluoropropylene oxide by using gas phase oxidation method | |
| CN102898303A (en) | Method for extracting methyl stearate from stearoylbenzoylmethane raffinate | |
| WO2021218275A1 (en) | Method for synthesizing and refining 4-fluorobenzoylacetonitrile | |
| CN116375746B (en) | A preparation method of potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |