CN105481645B - A kind of synthetic method of the propyl alcohol of (S) 1,1,1 trifluoro 2 - Google Patents
A kind of synthetic method of the propyl alcohol of (S) 1,1,1 trifluoro 2 Download PDFInfo
- Publication number
- CN105481645B CN105481645B CN201510866559.7A CN201510866559A CN105481645B CN 105481645 B CN105481645 B CN 105481645B CN 201510866559 A CN201510866559 A CN 201510866559A CN 105481645 B CN105481645 B CN 105481645B
- Authority
- CN
- China
- Prior art keywords
- trifluoro
- soxhlet
- catalyst
- hours
- extraction
- 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
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
- C07C29/74—Separation; Purification; Use of additives, e.g. for stabilisation
- C07C29/76—Separation; Purification; Use of additives, e.g. for stabilisation by physical treatment
- C07C29/86—Separation; Purification; Use of additives, e.g. for stabilisation by physical treatment by liquid-liquid treatment
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention discloses a kind of synthetic method of the propyl alcohol of (S) 1,1,1 trifluoro 2.Its step of, is as follows:It is 3~30 that mass ratio is added in the extraction flask of apparatus,Soxhlet's：1 n-hexane or cyclohexane solvent and 1, the propyl alcohol of 1,1 trifluoro 2, catalyst；In the extraction tube of apparatus,Soxhlet's, Novozyme435 is added；The top of the extraction tube of apparatus,Soxhlet's adds condenser, and condensing reflux reacts 10~24 hours；Reactant in apparatus,Soxhlet's extraction flask reacts 10~24 hours under reflux conditions, cooling, catalyst is recovered by filtration, concentration and recovery n-hexane or cyclohexane solvent, 10 20% sodium hydroxide or potassium hydroxide aqueous solution are added, reacted 5~10 hours, rectifying again, obtain the propyl alcohol of (S) 1,1,1 trifluoro 2.Raw material of the present invention is simple and easy to get, and course of reaction pollution is few, and technique is simple, and without complex device, securely and reliably, and synthesis yield is high, and the higher product of purity is obtained after refined.
Description
Technical field
The present invention relates to the synthetic method of compound, more particularly to a kind of (S) -1, the synthesis side of 1,1- Trifluoro-2-propanol
Method.
Background technology
(S) -1,1,1- Trifluoro-2-propanol, CAS：17628-73-8, it is a kind of important medicine, pesticide intermediate
(WO2014062196；WO2014086805；WO2014074668；WO2014154612；WO2013031922；
WO2013076063).Existing (S) -1, the synthetic method of 1,1- Trifluoro-2-propanol are as follows now：Jolley,Katherine
E. the method reduced by asymmetric hydrogenation is waited to synthesize (S) -1,1,1- Trifluoro-2-propanols (Advanced Synthesis＆
Catalysis, 354 (13), 2545-2555, S2545/1-S2545/67), react expensive catalyst used；Asano,
Yasuhisa etc. is catalyzed reduction synthesis (S) -1,1,1- Trifluoro-2-propanols (JP2012005396) by pichia farinose；
Rosen, Thomas C. etc. reduces to have obtained (S) -1,1,1- Trifluoro-2-propanols (Tetrahedron by alcohol dehydrogenase
Letters,47(28),4803-4806；2006), the method for both enzymatics is had to expensive coenzyme.Katayama,
Takeaki etc. has synthesized (S) -1,1,1- Trifluoro-2-propanols (EP2399895) by the method for asymmetric hydrogen migration, although keeping away
Exempt to use hydrogen, but catalyst is very expensive；Malek, Jaroslav etc. are synthesized with (-)-Quinine induction asymmetric reductions
(S) -1,1,1- Trifluoro-2-propanol (Organic Reactions, 34,1985), reducing agent employs inflammable and explosive aluminum hydride
Lithium；
The content of the invention
The present invention relates to a kind of (S) -1, the synthetic method of 1,1- Trifluoro-2-propanol, raw material of the present invention is simple and easy to get, reaction
Process contamination is few, and technique is simple, and without complex device, securely and reliably, and synthesis yield is high, and the higher production of purity is obtained after refined
Product.
N-hexane or cyclohexane solvent, solvent and 1,1,1- Trifluoro-2-propanol are added in the extraction flask of apparatus,Soxhlet's
Mass ratio be 3~30：1；Catalyst is added, catalyst and 1, the mass ratio of 1,1- Trifluoro-2-propanol is 0.01~0.1:1；
2) in the extraction tube of apparatus,Soxhlet's, Novozyme435, Novozyme435 and 1, the mass ratio of 1,1- Trifluoro-2-propanol are added
For 0.1~1:1.3) top of the extraction tube of apparatus,Soxhlet's adds condenser, and condensing reflux reacts 10~24 hours.4) Soxhlet carries
Take the reactant in device extraction flask to react under reflux conditions 10~24 hours, cool down, catalyst is recovered by filtration, concentration and recovery is just
Hexane or cyclohexane solvent, 10-20% sodium hydroxide or potassium hydroxide aqueous solution are added, reacted 5~10 hours, sodium hydroxide
Or the mass ratio of potassium hydroxide and 1,1,1- Trifluoro-2-propanols is 0.5~1：1, then rectifying, obtain (S) -1,1,1- tri- fluoro- 2-
Propyl alcohol.Described catalyst is Raney Ni or the Pd/C of 5% mass percentage content.
Embodiment
(S) the step of synthetic method of -1,1,1- Trifluoro-2-propanols is as follows:
1) it is 3~30 that mass ratio is added in the extraction flask of apparatus,Soxhlet's：1 n-hexane or cyclohexane solvent and 1,1,
1- Trifluoro-2-propanols；Catalyst is added, catalyst and 1, the mass ratio of 1,1- Trifluoro-2-propanol is 0.01~0.1:1；2) exist
The extraction tube of apparatus,Soxhlet's, adds Novozyme435, Novozyme435 and 1, and the mass ratio of 1,1- Trifluoro-2-propanol is
0.1~1:1.3) top of the extraction tube of apparatus,Soxhlet's adds condenser, and condensing reflux reacts 10~24 hours.4) surname extraction
Reactant in device extraction flask reacts 10~24 hours under reflux conditions, cooling, is recovered by filtration catalyst, concentration and recovery just oneself
Alkane or cyclohexane solvent, add 10-20% sodium hydroxide or potassium hydroxide aqueous solution, react 5~10 hours, sodium hydroxide or
The mass ratio of potassium hydroxide and 1,1,1- Trifluoro-2-propanols is 0.5~1：1, then rectifying, obtain (S) -1,1,1- tri- fluoro- 2- third
Alcohol.
Embodiment 1：
30 grams of n-hexane solvent and 10 grams of 1,1,1- Trifluoro-2-propanols in apparatus,Soxhlet's 500ml extraction flask；Add
Enter 0.1 gram of Raney Ni catalyst, in the extraction tube of apparatus,Soxhlet's, add 1 gram of Novozyme435, apparatus,Soxhlet's carries
The top of pipe is taken to add condenser, condensing reflux reacts 10 hours.Reactant in apparatus,Soxhlet's extraction flask is under reflux conditions
Reaction 10 hours, cooling, is recovered by filtration catalyst, concentration and recovery n-hexane or cyclohexane solvent, adds 10% sodium hydroxide
Or 50 grams of potassium hydroxide aqueous solution, react 5 hours, then rectifying, 81~82 DEG C of cuts are collected, obtain (S) -1,1,1- tri- fluoro- 2-
9.3 grams of propyl alcohol, yield 93%.GC is detected；Pillar:CP-Chiralsil-DexCB, 25m, 0.25mm, 0.25 μm, flow velocity=
2.0mL/min, 30 DEG C of stop 4min of method of testing, then 10 DEG C/min to 70 DEG C, 70 DEG C stop 10min. trifluoroacetones
1.07min, 1,1,1- Trifluoro-2-propanol 3.82min .ee value determine:Chromatographic column:GammaDex 225,30m x 0.25mm x
0.25 μm, flow velocity=5.0mL/min, 30 DEG C of method stops 4min and then 10 DEG C/min to 70 DEG C, three fluoro- 2- third of (R) -1,1,1-
Alcohol 5.530min, (S) -1,1,1- Trifluoro-2-propanols 5.760min..
Embodiment 2：
300 grams of cyclohexane solvent and the fluoro- 2- third of 10 grams of 1,1,1- tri- is added in apparatus,Soxhlet's 500ml extraction flask
Alcohol；1 gram of Raney Ni catalyst is added, in the extraction tube of apparatus,Soxhlet's, adds 10 grams of Novozyme435, apparatus,Soxhlet's
The top of extraction tube add condenser, condensing reflux reacts 24 hours.Reactant in apparatus,Soxhlet's extraction flask is in reflux condition
Reacted 24 hours under part, cool down, catalyst, concentration and recovery n-hexane or cyclohexane solvent is recovered by filtration, adds 20% hydrogen-oxygen
Change 50 grams of aqueous solutions of potassium, react 10 hours, then rectifying, 81~82 DEG C of cuts are collected, obtain (S) -1,1,1- Trifluoro-2-propanol
8.5 grams, yield 85%.
Embodiment 3：
The cyclohexane solvent and 10 grams of 1,1,1- that mass ratio is 100 grams are added in apparatus,Soxhlet's 500ml extraction flask
Trifluoro-2-propanol；The Pd/C catalyst of 1 gram of 5% mass percentage content is added, in the extraction tube of apparatus,Soxhlet's, adds 8 grams
Novozyme435, the top of the extraction tube of apparatus,Soxhlet's add condenser, and condensing reflux reacts 12 hours.Apparatus,Soxhlet's carries
Take the reactant in bottle to react under reflux conditions 12 hours, cool down, catalyst, concentration and recovery n-hexane or hexamethylene is recovered by filtration
Alkane solvents, 20% 25 grams of potassium hydroxide aqueous solution is added, reacted 8 hours, then rectifying, 81~82 DEG C of cuts are collected, are obtained
(S) -1,7.0 grams of 1,1- Trifluoro-2-propanol, yield 70%.
Claims (2)
1. a kind of (S) -1, the synthetic method of 1,1- Trifluoro-2-propanol, it is characterised in that it the step of it is as follows:
1）It is 3~30 that mass ratio is added in the extraction flask of apparatus,Soxhlet's：1 solvent and 1,1,1- Trifluoro-2-propanols；Add
Catalyst, catalyst and 1, the mass ratio of 1,1- Trifluoro-2-propanol is 0.01 ~ 0.1:1；2）In the extraction tube of apparatus,Soxhlet's,
The mass ratio for adding Novozyme435, Novozyme435 and 1,1,1- Trifluoro-2-propanol is 0.1 ~ 1:1； 3）Surname extraction
The top of the extraction tube of device adds condenser, and the reactant in apparatus,Soxhlet's extraction flask reacts 10 ~ 24 hours under reflux conditions,
Cooling, is recovered by filtration catalyst, concentration and recovery solvent, adds 10-20% sodium hydroxide or potassium hydroxide aqueous solution, hydroxide
The mass ratio of sodium or potassium hydroxide and 1,1,1- Trifluoro-2-propanols is 0.5 ~ 1：1, react 5 ~ 10 hours, then rectifying, obtain
(S) -1,1,1- Trifluoro-2-propanols；Described catalyst is Raney Ni or the Pd/C of 5% mass percentage content.
2. one kind (S) -1 according to claim 1, the synthetic method of 1,1- Trifluoro-2-propanol, it is characterised in that described
Solvent is n-hexane or hexamethylene.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510866559.7A CN105481645B (en) | 2015-12-01 | 2015-12-01 | A kind of synthetic method of the propyl alcohol of (S) 1,1,1 trifluoro 2 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510866559.7A CN105481645B (en) | 2015-12-01 | 2015-12-01 | A kind of synthetic method of the propyl alcohol of (S) 1,1,1 trifluoro 2 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105481645A CN105481645A (en) | 2016-04-13 |
| CN105481645B true CN105481645B (en) | 2017-12-15 |
Family
ID=55668969
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510866559.7A Active CN105481645B (en) | 2015-12-01 | 2015-12-01 | A kind of synthetic method of the propyl alcohol of (S) 1,1,1 trifluoro 2 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105481645B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110194781B (en) * | 2018-02-27 | 2023-12-08 | 上海奥普迪诗化学科技有限公司 | Preparation method of 1,1' -bis (diphenylphosphine) ferrocene palladium dichloride dichloromethane complex |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AT502185B1 (en) * | 2005-09-23 | 2007-02-15 | Iep Gmbh | Enantioselective enzymatic reduction of keto compound comprises treating a liquid, two-phase mixture with an oxidoreductase in the presence of co-factors to obtain a chiral hydroxy compound |
| CN101501202A (en) * | 2006-06-05 | 2009-08-05 | 大赛璐化学工业株式会社 | Process for production of optically active alcohol |
| JP5631641B2 (en) * | 2010-06-23 | 2014-11-26 | 富山県 | Industrial production method of (R) -1,1,1-trifluoro-2-propanol |
| CN104894169B (en) * | 2015-05-28 | 2019-02-15 | 苏州汉酶生物技术有限公司 | A kind of preparation method of (S) -1,1,1- Trifluoroisoproanol |
-
2015
- 2015-12-01 CN CN201510866559.7A patent/CN105481645B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN105481645A (en) | 2016-04-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102675176B (en) | A kind of be raw material production caprolactam with high pure benzene method | |
| JP2014507381A5 (en) | ||
| MX2015008028A (en) | Method for producing acetic acid. | |
| WO2009063487A3 (en) | An improved process for manufacture of epoxides, particularly epichlorohydrin | |
| CN107304168A (en) | Distillation purifying with segregator for prepurification IPD is coupled | |
| CN104603095A (en) | Method for producing menthone from isopulegol | |
| TWI720968B (en) | Isomerization method for bis(aminomethyl)cyclohexane | |
| CN112321389B (en) | Preparation method of yellowing-resistant L-menthol | |
| CN105481645B (en) | A kind of synthetic method of the propyl alcohol of (S) 1,1,1 trifluoro 2 | |
| CN103373915B (en) | A kind of catalytic oxidation prepares the method for di-carboxylic acid | |
| CN107365244B (en) | Method for preparing 1H-perhalo cyclic olefin by hydrogen-halogen exchange reaction through hydrogen source provided by organic solvent | |
| CN102421737A (en) | Method for preparing a terpenylcyclohexanol | |
| RU2016142388A (en) | METHOD FOR PRODUCING FURANA FROM FURFUROL | |
| CN113260603B (en) | Preparation of 5-aryl pentanols | |
| KR20150095930A (en) | Method for the production of purified caprolactam from the beckmann rearrangement of cyclohexanone oxime | |
| CN105461516B (en) | A kind of synthesis technique of L menthols | |
| CN102924411A (en) | Synthesis method of triptolide intermediate | |
| CN101973837B (en) | Method for purifying beta-pinene | |
| CN104974017A (en) | Preparation method of (1R,2S)-2-(3,4-difluorophenyl) rolicyprine.D-mandelate | |
| CN101973838B (en) | Method for purifying beta-pinene and preparing alpha-epoxy pinane from turpentine oil | |
| CN103601708A (en) | Preparation method of prostaglandin medicine impurity | |
| JP6003755B2 (en) | Lactam purification method | |
| CN105693455A (en) | Synthetic method for 1,5,9-cyclododecatriene | |
| CN102786407B (en) | Method of preparing (2R)-2-propyl caprylic acid | |
| CN104177268B (en) | A kind of preparation method of 1-[2-amino-1-(4-p-methoxy-phenyl) ethyl] hexalin |
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 | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20180913 Address after: 315700 Dandong Road, Xiangshan County, Ningbo, Zhejiang, No. 4585 Patentee after: Ningbo Jin Wei Biotechnology Co., Ltd. Address before: 310023 Xihu District, Hangzhou, Hangzhou, Zhejiang Province, No. 318 Patentee before: Zhejiang University of Science and Technology |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20181206 Address after: 318000 29 Binhai Road, Jiaojiang District, Taizhou, Zhejiang Patentee after: Zhejiang Le Pu pharmaceutical Limited by Share Ltd Address before: 315700 Dandong Road, Xiangshan County, Ningbo, Zhejiang, No. 4585 Patentee before: Ningbo Jin Wei Biotechnology Co., Ltd. |
|
| TR01 | Transfer of patent right |