CN107501044A - The preparation method of Pentafluorobenzyl pentanol - Google Patents
The preparation method of Pentafluorobenzyl pentanol Download PDFInfo
- Publication number
- CN107501044A CN107501044A CN201710768052.7A CN201710768052A CN107501044A CN 107501044 A CN107501044 A CN 107501044A CN 201710768052 A CN201710768052 A CN 201710768052A CN 107501044 A CN107501044 A CN 107501044A
- Authority
- CN
- China
- Prior art keywords
- reaction
- preparation
- initiator
- pentafluorobenzyl pentanol
- pentafluorobenzyl
- 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.)
- Withdrawn
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/58—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by elimination of halogen, e.g. by hydrogenolysis, splitting-off
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/62—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by introduction of halogen; by substitution of halogen atoms by other halogen atoms
Abstract
The invention discloses a kind of preparation method of Pentafluorobenzyl pentanol, comprise the following steps：（ⅰ）Synthetic reaction：Propenyl and the PFEI amylalcohol of 2 iodine of reaction 4,4,5,5,5 5 fluorine of generation 1 under radical initiator effect；（ⅱ）Hydrodehalogenation reacts：Hydrodehalogenation reaction generation Pentafluorobenzyl pentanol product occurs in the presence of reducing agent for the amylalcohol of 4,4,5,5,5 5 fluorine, 2 iodine 1.The invention provides a kind of preparation method of Pentafluorobenzyl pentanol, radical reaction generation 4 is occurred as raw material using PFEI and propenyl, 4, the amylalcohol of 5,5,5 five fluorine, 2 iodine 1, dehalogenation reaction generation Pentafluorobenzyl pentanol occurs under reducing agent effect again, not only reaction yield is high for the method, is easy to industrialized production, and product purity is more than 99%.
Description
Technical field
The invention belongs to a kind of preparation method of synthetic intermediate, and in particular to a kind of preparation method of Pentafluorobenzyl pentanol.
Background technology
Pentafluorobenzyl pentanol, molecular formula are C5H7F5O, main application are antineoplastic intermediate, and downstream product is five fluorine of production
Amyl hydrosulfide, Pentafluorobenzyl pentanol are applied to the intermediate and some medicine preparations of new and effective pharmaceutical synthesis, and surface in recent years
Activating agent, functional material, the synthetic intermediate of inert fluid and dye industry, purposes are quite varied.
Pentafluorobenzyl pentanol preparation technology reported in the literature mainly has three kinds, and two of which process route is with PFEI
It is raw material with propenyl.The first process route is to be used as radical initiator using sodium dithionite/sodium bicarbonate mixture
4,4,5,5, the 5- five fluoro- iodo- 2- amylene-1-ols of 2- are generated, aoxidizes and generates five fluorine after hydrodehalogenation occurs with hydrogen under platinum catalysis
Amylalcohol.The shortcomings that process route is that catalyst amount is larger, expensive.Second of process route is to use perfluoroalkyl copper
4,4,5,5,5- five fluoro- 2- amylene-1-ols are generated for raw material, hydrogenation reaction occurs as catalyst using platinum oxide or Raney's nickel
Generate Pentafluorobenzyl pentanol.The dosage of the process route used catalyst is only the 5% of the first process route, but the process route
Overall yield it is relatively low, cost is higher.
The third process route is to use PFEI and allyl acetate as raw material, the use of azodiisobutyronitrile is to urge
Agent, the amyl fluorides of generation 5- acetoxyl groups -4- iodo- 1,1,1,2,2- five.The iodo- fluorine penta of 1,1,1,2,2- five of 5- acetoxyl groups -4-
Under tri-butyl tin hydride effect dehalogenation reaction occurs for alkane, generates 5- acetoxyl groups -1,1,1,2,2- five amyl fluoride.5- acetyl oxygen
The amyl fluorides of base -1,1,1,2,2- five hydrolyze generation Pentafluorobenzyl pentanol in the presence of alkali.But the shortcomings that process route is reaction
Process is difficult to control, it is difficult to realizes industrialization.
Pentafluorobenzyl pentanol product purity prepared by these three process routes is respectively less than 95%, can not meet the market demand.
The content of the invention
The present invention proposes that the purpose is to provide a kind of Pentafluorobenzyl pentanol in order to overcome shortcoming present in prior art
Preparation method.
The technical scheme is that：
A kind of preparation method of Pentafluorobenzyl pentanol, comprises the following steps：
（ⅰ）Synthetic reaction
Propenyl, PFEI, radical initiator and reaction dissolvent are added in reaction vessel according to certain ratio, in
To be reacted certain time under certain temperature, reaction stands after terminating and separates lower floor's organic phase, and organic phase produces 4,4 through washing and drying,
The iodo- 1- amylalcohols of five fluoro- 2- of 5,5,5-；
（ⅱ）Hydrodehalogenation reacts
By step（ⅰ）The iodo- 1- amylalcohols of five fluoro- 2- of gained 4,4,5,5,5-, reducing agent and azo type free radical initiator are according to one
Fixed ratio is added in reaction vessel, is reacted certain time under certain temperature, and reaction stands after terminating and separates upper organic phase,
Produce Pentafluorobenzyl pentanol product.
The radical initiator is organic peroxide either in oxidation-reduction initiator or azo-initiator
Any one.
The reaction dissolvent is water or the mixed liquor of acetonitrile and water.
The reaction temperature is 30 DEG C ~ 70 DEG C, and the reaction time is 4h ~ 8h.
The organic peroxide is isopropyl benzene hydroperoxide, TBHP, acetyl peroxide, benzoyl peroxide first
Any one in acyl, dibenzoyl peroxide, cyclohexanone peroxide；The oxidation-reduction initiator is that hydrogen peroxide/sulfuric acid is sub-
Any one in iron mixture or ammonium persulfate/sodium hydrogensulfite mixture；The azo-initiator is that azo two is different
Any one in butyronitrile initiator or ABVN initiator.
The mixed liquor reclaimed water of the acetonitrile and water and the mass ratio of acetonitrile are 1：5~15.
The propenyl, the mass ratio of PFEI are 1：2~7.
The mass ratio of the radical initiator and propenyl is 1:0.05~0.2；The matter of the reaction dissolvent and propenyl
Amount is than being 1：1~3.
The reducing agent is any one in noble metal catalyst or cupric oxide-copper chromite；The noble metal is urged
Agent is platinum oxide, palladium-charcoal, palladium-iron, palladium, [RuCl2(p-cymene)]2, any one in Raney's nickel.
The step（ⅱ）The input quality of middle azo type free radical initiator is the iodo- 1- penta of five fluoro- 2- of 4,4,5,5,5-
The 10%-40% of the quality of alcohol, reaction temperature are 60 DEG C -90 DEG C.
The beneficial effects of the invention are as follows：
The invention provides a kind of preparation method of Pentafluorobenzyl pentanol, and it is anti-that free radical occurs using PFEI and propenyl as raw material
4,4,5,5, the 5- five fluoro- iodo- 1- amylalcohols of 2- should be generated, then dehalogenation reaction generation Pentafluorobenzyl pentanol occurs under reducing agent effect, this
Not only reaction yield is high for method, is easy to industrialized production, and product purity is more than 99%.
Embodiment
The preparation method of Pentafluorobenzyl pentanol of the present invention is described in detail with reference to embodiment：
A kind of preparation method of Pentafluorobenzyl pentanol, comprises the following steps：
（ⅰ）Synthetic reaction
Propenyl, PFEI, radical initiator and reaction dissolvent are added in reaction vessel according to certain ratio, in
To be reacted certain time under certain temperature, reaction stands after terminating and separates lower floor's organic phase, and organic phase produces 4,4 through washing and drying,
The iodo- 1- amylalcohols of five fluoro- 2- of 5,5,5-；
Reaction equation is：
（ⅱ）Hydrodehalogenation reacts
By step（ⅰ）The iodo- 1- amylalcohols of five fluoro- 2- of gained 4,4,5,5,5-, reducing agent and azo type free radical initiator are according to one
Fixed ratio is added in reaction vessel, is reacted certain time under certain temperature, and reaction stands after terminating and separates upper organic phase,
Produce Pentafluorobenzyl pentanol product.
Reaction equation is：
The radical initiator is that organic peroxide is either any in oxidation-reduction initiator or azo-initiator
It is a kind of.
The reaction dissolvent is water or the mixed liquor of acetonitrile and water.
The reaction temperature is 30 DEG C ~ 70 DEG C, and the reaction time is 4h ~ 8h.
The organic peroxide is isopropyl benzene hydroperoxide, TBHP, acetyl peroxide, benzoyl peroxide first
Any one in acyl, dibenzoyl peroxide, cyclohexanone peroxide；The oxidation-reduction initiator is that hydrogen peroxide/sulfuric acid is sub-
Any one in iron mixture or ammonium persulfate/sodium hydrogensulfite mixture；The azo-initiator is that azo two is different
Any one in butyronitrile initiator or ABVN initiator.
The mixed liquor reclaimed water of the acetonitrile and water and the mass ratio of acetonitrile are 1：5~15.
The propenyl, the mass ratio of PFEI are 1：2~7.
The mass ratio of the radical initiator and propenyl is 1:0.05~0.2；The matter of the reaction dissolvent and propenyl
Amount is than being 1：1~3.
The reducing agent is any one in noble metal catalyst or cupric oxide-copper chromite；The noble metal is urged
Agent is platinum oxide, palladium-charcoal, palladium-iron, palladium, [RuCl2(p-cymene)]2, any one in Raney's nickel.
The step（ⅱ）The input quality of middle azo type free radical initiator is the iodo- 1- penta of five fluoro- 2- of 4,4,5,5,5-
The 10%-40% of the quality of alcohol, reaction temperature are 60 DEG C -90 DEG C.
Embodiment 1
（ⅰ）110g propenyls and 500g PFEIs are added in autoclave pressure, adds 15g azodiisobutyronitriles, adds water
800ml, it is 30 DEG C ~ 40 DEG C to control temperature, stirring reaction 4h ~ 8h.Reaction stands after terminating and separates lower floor's organic phase, organic phase water
Dry 4,4,5,5, the 5- five fluoro- iodo- 1- amylalcohols 600g of 2-, purity 90% after washing.
（ⅱ）50g azodiisobutyronitriles are added in the fluoro- iodo- 1- amylalcohols of 2- of 500g 4,4,5,5,5- five, are slowly added to
40g platinum-oxide catalysts, controlling reaction temperature are 60 DEG C ~ 70 DEG C, react 3h-4h.It is organic to separate upper strata for standing after completion of the reaction
Pentafluorobenzyl pentanol product is mutually produced, quality 260g, product rectification and purification is obtained into Pentafluorobenzyl pentanol product of the purity more than 99%.
Embodiment 2
（ⅰ）110g propenyls and 600g PFEIs are added in autoclave pressure, adds 20g isopropyl benzene hydroperoxides, adds water
700ml, acetonitrile 100ml, it is 40 DEG C ~ 50 DEG C to control temperature, stirring reaction 4h ~ 8h.It is organic to separate lower floor for standing after reaction terminates
Phase, dry 4,4,5,5, the 5- five fluoro- iodo- g of 1- amylalcohols 610 of 2- after organic phase washing, purity 89%.
（ⅱ）40g ABVNs are added in the fluoro- iodo- 1- amylalcohols of 2- of 500g 4,4,5,5,5- five, are slowly added to
40g 5% palladium-Pd/carbon catalyst, controlling reaction temperature are 60 DEG C ~ 70 DEG C, react 3h-4h.Filter after completion of the reaction and produce five fluorine penta
Alcohol product, quality 260g, product rectification and purification is obtained into Pentafluorobenzyl pentanol product of the purity more than 99%.
Embodiment 3
（ⅰ）110g propenyls and 400g PFEIs are added in autoclave pressure, adds 50g ammonium persulfates, 25g bisulfites
Sodium, water 900ml is added, it is 50 DEG C ~ 70 DEG C to control temperature, stirring reaction 4h ~ 8h.It is organic to separate lower floor for standing after reaction terminates
Phase, dry 4,4,5,5, the 5- five fluoro- iodo- 1- amylalcohols 600g of 2- after organic phase washing.
（ⅱ）30g azodiisobutyronitriles are added in the fluoro- iodo- 1- amylalcohols of 2- of 500g 4,4,5,5,5- five, are slowly added to
50g palladiums, controlling reaction temperature are 60 DEG C ~ 70 DEG C, react 3h-4h.Filter after completion of the reaction and produce Pentafluorobenzyl pentanol product, matter
Measure as 260g, product rectification and purification is obtained into the Pentafluorobenzyl pentanol product that purity is more than 99%.
Claims (10)
- A kind of 1. preparation method of Pentafluorobenzyl pentanol, it is characterised in that：Comprise the following steps：（ⅰ）Synthetic reactionPropenyl, PFEI, radical initiator and reaction dissolvent are added in reaction vessel according to certain ratio, in To be reacted certain time under certain temperature, reaction stands after terminating and separates lower floor's organic phase, and organic phase produces 4,4 through washing and drying, The iodo- 1- amylalcohols of five fluoro- 2- of 5,5,5-；（ⅱ）Hydrodehalogenation reactsBy step（ⅰ）The iodo- 1- amylalcohols of five fluoro- 2- of gained 4,4,5,5,5-, reducing agent and azo type free radical initiator are according to one Fixed ratio is added in reaction vessel, is reacted certain time under certain temperature, and reaction stands after terminating and separates upper organic phase, Produce Pentafluorobenzyl pentanol product.
- A kind of 2. preparation method of Pentafluorobenzyl pentanol according to claim 1, it is characterised in that：The radical initiator is Organic peroxide either any one in oxidation-reduction initiator or azo-initiator.
- A kind of 3. preparation method of Pentafluorobenzyl pentanol according to claim 1, it is characterised in that：The reaction dissolvent be water or The mixed liquor of person's acetonitrile and water.
- A kind of 4. preparation method of Pentafluorobenzyl pentanol according to claim 1, it is characterised in that：The reaction temperature is 30 DEG C ~ 70 DEG C, the reaction time is 4h ~ 8h.
- A kind of 5. preparation method of Pentafluorobenzyl pentanol according to claim 2, it is characterised in that：The organic peroxide is Isopropyl benzene hydroperoxide, TBHP, acetyl peroxide, benzoyl peroxide, dibenzoyl peroxide, peroxidating ring Any one in hexanone；The oxidation-reduction initiator is hydrogen peroxide/ferrous sulfate mixture or ammonium persulfate/sulfurous Any one in sour hydrogen sodium mixture；The azo-initiator is azodiisobutyronitrile initiator or ABVN Any one in initiator.
- A kind of 6. preparation method of Pentafluorobenzyl pentanol according to claim 3, it is characterised in that：The mixing of the acetonitrile and water The mass ratio of liquid reclaimed water and acetonitrile is 1：5~15.
- A kind of 7. preparation method of Pentafluorobenzyl pentanol according to claim 1, it is characterised in that：The propenyl, five fluorine iodine The mass ratio of ethane is 1：2~7.
- A kind of 8. preparation method of Pentafluorobenzyl pentanol according to claim 1, it is characterised in that：The radical initiator with The mass ratio of propenyl is 1:0.05~0.2；The mass ratio of the reaction dissolvent and propenyl is 1：1~3.
- A kind of 9. preparation method of Pentafluorobenzyl pentanol according to claim 1, it is characterised in that：The reducing agent is noble metal Any one in catalyst or cupric oxide-copper chromite；The noble metal catalyst is platinum oxide, palladium-charcoal, palladium-iron, vinegar Sour palladium, [RuCl2(p-cymene)]2, any one in Raney's nickel.
- A kind of 10. preparation method of Pentafluorobenzyl pentanol according to claim 1, it is characterised in that：The step（ⅱ）Middle idol The input quality of nitrogen type free base initiator is the 10%-40% of the quality of 4,4,5,5, the 5- five fluoro- iodo- 1- amylalcohols of 2-, reacts temperature Spend for 60 DEG C -90 DEG C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710768052.7A CN107501044A (en) | 2017-08-31 | 2017-08-31 | The preparation method of Pentafluorobenzyl pentanol |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710768052.7A CN107501044A (en) | 2017-08-31 | 2017-08-31 | The preparation method of Pentafluorobenzyl pentanol |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107501044A true CN107501044A (en) | 2017-12-22 |
Family
ID=60694366
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710768052.7A Withdrawn CN107501044A (en) | 2017-08-31 | 2017-08-31 | The preparation method of Pentafluorobenzyl pentanol |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107501044A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109678672A (en) * | 2018-12-17 | 2019-04-26 | 常州市灵达化学品有限公司 | A kind of preparation method of perfluoroalkyl propyl alcohol |
| CN110981690A (en) * | 2019-12-12 | 2020-04-10 | 西安近代化学研究所 | Preparation method of 4,4,5,5, 5-penta-fluoropentanol |
| CN111004091A (en) * | 2019-12-12 | 2020-04-14 | 西安近代化学研究所 | Method for preparing 4,4,5,5, 5-penta-fluoropentanol |
| CN116162016A (en) * | 2023-01-09 | 2023-05-26 | 山东重山光电材料股份有限公司 | Preparation method of high-purity pentafluoropentanol |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6002053A (en) * | 1997-10-14 | 1999-12-14 | Bayer Aktiengesellschaft | Process for preparing pentafluoropentanol |
| JP2003146921A (en) * | 2001-11-08 | 2003-05-21 | Daikin Ind Ltd | Method for producing perfluoroalkyl compound |
| EP2196449A1 (en) * | 2008-12-12 | 2010-06-16 | Saltigo GmbH | Method for producing perfluoralkyl or perfluoralkoxyalkanoles |
-
2017
- 2017-08-31 CN CN201710768052.7A patent/CN107501044A/en not_active Withdrawn
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6002053A (en) * | 1997-10-14 | 1999-12-14 | Bayer Aktiengesellschaft | Process for preparing pentafluoropentanol |
| JP2003146921A (en) * | 2001-11-08 | 2003-05-21 | Daikin Ind Ltd | Method for producing perfluoroalkyl compound |
| EP2196449A1 (en) * | 2008-12-12 | 2010-06-16 | Saltigo GmbH | Method for producing perfluoralkyl or perfluoralkoxyalkanoles |
Non-Patent Citations (3)
| Title |
|---|
| J. D. PARK,等: "Free-Radical Catalyzed Addition of Unsaturated Alcohols to Perhaloalkanes", 《J.ORG.CHEM.》 * |
| ULF LARSSON, 等: "Synthesis of Amino Acids with Modified Principal Properties 1. Amino Acids with Fluorinated Side Chains", 《ACTA CHEMICA SCANDINAVICA》 * |
| XUN LI, 等: "Laboratory scale Preparation of 4,4,5,5,5-Pentafluoropentan-1-thiol: An Important Chain of Anti-Breast Cancer Agents", 《TETRAHEDRON LETTERS》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109678672A (en) * | 2018-12-17 | 2019-04-26 | 常州市灵达化学品有限公司 | A kind of preparation method of perfluoroalkyl propyl alcohol |
| CN110981690A (en) * | 2019-12-12 | 2020-04-10 | 西安近代化学研究所 | Preparation method of 4,4,5,5, 5-penta-fluoropentanol |
| CN111004091A (en) * | 2019-12-12 | 2020-04-14 | 西安近代化学研究所 | Method for preparing 4,4,5,5, 5-penta-fluoropentanol |
| CN116162016A (en) * | 2023-01-09 | 2023-05-26 | 山东重山光电材料股份有限公司 | Preparation method of high-purity pentafluoropentanol |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107501044A (en) | The preparation method of Pentafluorobenzyl pentanol | |
| CN112142570B (en) | Preparation method of p-hydroxybiphenyl diphenol | |
| CN102584665B (en) | Method for preparing 75 mass percent solvent based cumyl peroxyneodecanoate | |
| CN102558399B (en) | Preparation method of solvent-based tert-butyl peroxyneo-caprate with mass fraction of 75% | |
| CN110590703B (en) | Green synthesis method of rubber vulcanization accelerator dibenzothiazyl disulfide | |
| CN111517931A (en) | Method for synthesizing 2, 4-difluorobenzaldehyde by using microchannel reactor | |
| CN107098790A (en) | A kind of method for preparing high-purity octafluoropropane | |
| CN102675048B (en) | Method for synthesizing prenol by composite catalyst | |
| CN102464633B (en) | Synthetic method for (methyl) glycidyl acrylate | |
| CN109174178A (en) | A kind of alumina load ionic liquid-palladium catalyst and its preparation and the application in ethylene front-end hydrogenation reaction | |
| CN102585048A (en) | Preparation method of 70% mass fraction of solvent type cumyl peroxyneodecanoate | |
| CN104549522A (en) | Mercury-free catalyst for preparation of VCM (vinyl chloride monomer) through acetylene hydrochlorination and using method | |
| CN106748906B (en) | A kind of synthetic method of bumetanide | |
| JP4004858B2 (en) | Method for producing acrylic acid polymer | |
| CN110947375B (en) | Catalyst for preparing propylene oxide and preparation method thereof | |
| CN107793289A (en) | A kind of preparation method of 2,3,5 trifluorobromobenzene | |
| CN109879599A (en) | A kind of preparation process of display screen reduction processing liquid | |
| CN111548295B (en) | Preparation method of di (2-ethylhexyl) peroxydicarbonate | |
| CN110813352B (en) | Ni2Preparation method of P/NC catalyst, Ni2P/NC catalyst and application thereof | |
| CN106831362A (en) | The production method of 2 propoxyl group chloroethanes | |
| CN107628933A (en) | A kind of continuous production technology that the acetone of 1 methoxyl group 2 is synthesized by the propyl alcohol direct dehydrogenation of 1 methoxyl group 2 | |
| CN109867745B (en) | Polyacrylonitrile resin and preparation method thereof | |
| CN111004091A (en) | Method for preparing 4,4,5,5, 5-penta-fluoropentanol | |
| CN108080027A (en) | A kind of resin catalyst treatment process of liquid phase Beckmann rearrangement caprolactam | |
| CN104860276B (en) | Method for reducing dilute nitric acid to nitrous acid |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20171222 |
|
| WW01 | Invention patent application withdrawn after publication |