CN102503776A - Method for synthesizing propofol by utilizing aluminum catalyst taking reactant 2-isopropyl phenol as ligand - Google Patents
Method for synthesizing propofol by utilizing aluminum catalyst taking reactant 2-isopropyl phenol as ligand Download PDFInfo
- Publication number
- CN102503776A CN102503776A CN2011103689578A CN201110368957A CN102503776A CN 102503776 A CN102503776 A CN 102503776A CN 2011103689578 A CN2011103689578 A CN 2011103689578A CN 201110368957 A CN201110368957 A CN 201110368957A CN 102503776 A CN102503776 A CN 102503776A
- Authority
- CN
- China
- Prior art keywords
- isopropyl
- phenol
- propofol
- reaction
- reactant
- 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.)
- Pending
Links
Images
Classifications
-
- 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
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a method for synthesizing a propofol by utilizing an aluminum catalyst taking a reactant 2-isopropyl phenol as a ligand. The method comprises the following steps: (1) preparing a catalyst, namely, 2-isopropyl phenol aluminum, by using the 2-isopropyl phenol and aluminum powder; (2) utilizing sodium to dry and dewater a solvent; and (3) in the solvent, synthesizing the propofol by utilizing the raw material propylene and the 2-isopropyl phenol under the existence of the catalyst, namely, the 2-isopropyl phenol aluminum. According to the method, the cost is saved; the source for generating impurities is reduced; and the purity of products is increased. The high-purity 2-isopropyl phenol is taken as the raw material and the 2-isopropyl phenol aluminum is taken as the catalyst, so that the selectivity of O-isopropyl is enhanced, the generation of byproducts is reduced, and the yield and purity are increased; the reaction is performed in a specific solvent methylbenzene, so that the exothermic reaction can be conveniently performed, and meanwhile, the reaction can be easily controlled; and during the reaction, olefin is taken as the reactant, and a gas reagent is used for conveniently monitoring the reaction process through the pressure control.
Description
Technical field
The present invention relates to a kind of chemical technique, being specifically related to a kind of is the method that the Al catalysts of part is used for synthetic Propofol with reactant 2-isopropyl-phenol.
Background technology
Propofol has another name called Disoprivan, English name: propofol, and chemical name: 2, the 6-diisopropyl phenol, (2,6-Bis (1-methylethyl) phenol) structural chemistry formula is following:
Propofol be generally be used for clinically at present anesthesia induction, anesthesia keep, a kind of novel quick, fugitive intravenous anesthetic of ICU urgent patient sedative.It has anesthesia induction rapid-action, revive rapidly and functional rehabilitation perfect, advantage such as the postoperative nausea and vomiting incidence is low.
Usually the compound method of Propofol is a catalyzer with phenol aluminium; Under high temperature and high pressure, adopt the alkylated reaction of phenol and propylene to obtain; Described like the 98112478.X one Chinese patent application; Wherein related to the reaction of under HTHP, adopting catalyzer, weak point is that by product is many, and raw material availability is not high.It is catalyzer that the aluminum alkyls of employing is also arranged; React with same ortho position substituted phenol and alkene and to obtain Propofol, weak point is the easy oxidation of catalyzer, and very active; There is danger greatly, utilizes this method synthesizing exactly like No. 200910140403.5 one Chinese patent application.Simultaneously, also have many bibliographical informations adopt phenol and Virahol at high temperature (300-350 ℃) be the synthetic Propofol of catalyst reaction with the aluminium sesquioxide, but more than the sub product and temperature high limited its application (
J. Org. Chem.
1980, 45,4326).Also there is report to adopt microwave to promote that the thinking of the ether deprotection under ionic liquid is synthesized phenols down, but need the cost of raw material very high in this way (
Synlett,
2010, 11,1651), be unfavorable for industriallization.For drug safety, we adopt catalyzer cheap and easy to get and the synthetic high Propofol of purity of raw material as far as possible.
Summary of the invention
In order to overcome the deficiency of above-mentioned prior art, it is the method that the Al catalysts of part is used for synthetic Propofol with reactant 2-isopropyl-phenol that the present invention will provide a kind of, and this method is than other preparation methods; Reduced the introducing of complicated ingredient; Can reduce source and production of by-products that impurity produces like this, increase ortho-isopropylated selectivity, simultaneously; This method can improve utilization ratio of raw materials; Practice thrift cost, and adopted this catalyst efficient high, improved the productive rate and the purity of Propofol; Be reflected in the specific solvent toluene and carry out, be convenient to the carrying out of this thermopositive reaction, also control easily simultaneously and should react; In addition, present method is convenient to come the monitoring reaction process through the control of pressure.
The scheme of accomplishing the foregoing invention task is: a kind of is the method that the Al catalysts of part prepares Propofol with reactant 2-isopropyl-phenol, it is characterized in that step is following,
⑴. prepare catalyzer 2-isopropyl-phenol aluminium with 2-isopropyl-phenol and aluminium powder;
⑵. solvent dewaters through the sodium drying;
⑶. in solvent, raw material propylene and 2-isopropyl-phenol, in the presence of catalyzer 2-isopropyl-phenol aluminium, synthetic Propofol.
The synthetic route of this method is as follows:
Among the preparation method of the present invention,
Said step ⑴ is under 200 ~ 210 ℃ of temperature, to prepare used catalyzer with 2-isopropyl-phenol and aluminium powder earlier.
The solvent of said step ⑵ and step ⑶ can adopt benzene, toluene or YLENE, and the present invention recommends to adopt toluene.
Said step ⑶ is with propylene and 2-isopropyl-phenol synthetic Propofol under catalysis.Wherein temperature of reaction is 70 ~ 140 ℃, and pressure is about 0.5 ~ 3.0 Mpa, and the reaction times is about 0.5 ~ 4 h.Wherein 2-isopropyl-phenol purity should be higher than 99%.
The present invention recommends, and best temperature of reaction is 90 ~ 100 ℃, and pressure is about 1.5 ~ 2.0 Mpa, and the reaction times is about 3 h.
Propylene wherein: 2-isopropyl-phenol: 2-isopropyl-phenol aluminium: the mass volume ratio=1:0.5 of solvent ~ 0.7:0.09 ~ 0.11:42 ~ 44.
The optimum value of mass volume ratio is propylene: the 2-isopropyl-phenol: 2-isopropyl-phenol aluminium: the mass volume ratio=1:0.6:0.1:43 of solvent.
Described mass volume ratio is meant: the quality (g) of 2-isopropyl-phenol and 2-isopropyl-phenol aluminium, and the ratio of the volume (mL) of propylene and solvent.
Present method has been used to accomplish as the Al catalysts of part with reaction raw materials and has been paid a gram alkylated reaction and prepare Propofol, and reactant has adopted 2-isopropyl-phenol and propylene, and the solvent of prioritization scheme has adopted toluene, and single stage method is synthetic, and aftertreatment is simple relatively.
The present invention has following advantage:
1, adopting with the reactant is the Al catalysts of part, compares with known catalysts, can improve raw material availability (seeing accompanying drawing 3,4).
2, be raw material with highly purified 2-isopropyl-phenol, 2-isopropyl-phenol aluminium is catalyzer, can increase ortho-isopropylated selectivity, has reduced production of by-products, compared with prior art, has improved product purity and yield (seeing accompanying drawing 1,2);
3, adopting with the reactant is the Al catalysts of part, be simple and easy to, reduced the introducing of other compositions, reduce the source that impurity produces, and practiced thrift cost.
4, be reflected in the specific solvent toluene and carry out, be convenient to the carrying out of this thermopositive reaction, also control should reaction easily simultaneously;
5, reaction employing alkene is reactant, and gaseous reagent is convenient to come the monitoring reaction process through the control of pressure.
Description of drawings
Fig. 1 is the HPLC test curve figure of prior art (commercially available) Propofol, and following form is the explanation of this graphic representation;
Fig. 2 is the HPLC test curve figure of synthetic Propofol of the present invention, and following form is the explanation of this graphic representation.
Fig. 3 is that the embodiment of the invention 1 reaction finishes, reaction solution TLC pattern, and visible raw material 2-isopropyl-phenol reacts completely.
Fig. 4 is for being that catalyst reaction finishes with the triethyl aluminum, and reaction solution TLC pattern has part 2-isopropyl-phenol not participate in reaction.
Embodiment
Embodiment 1, is the method that the Al catalysts of part prepares Propofol with reactant 2-isopropyl-phenol, and step is following, gets the 5g aluminium powder and adds in the 100 mL single port bottles magnetic agitation to aluminium powder black in color metalluster; Then in above-mentioned single port bottle, add 50g 2-isopropyl-phenol, under the nitrogen protection condition, be warming up to 200 ~ 210 ℃, the about 2h of stirring and refluxing.After treating that above-mentioned feed liquid is cooled to room temperature, it is transferred in the autoclave of 5 L with 2000 mL exsiccant toluene; Fall the air in the still with nitrogen replacement; Slowly feed propylene gas to still internal force then and be about 1.0 Mpa; Be warming up to 90 ~ 100 ℃, this moment, the still internal pressure was about 1.5 ~ 2.0 Mpa, the about 3h of stirring reaction; Reaction is finished thin-layer chromatography (TLC) and is detected, and (developping agent is sherwood oil: ETHYLE ACETATE=20:1 for result such as Fig. 3; R
The f Propofol=0.7).Above-mentioned reaction solution is cooled to room temperature, transfers to then in the beaker, with 1% aqueous hydrochloric acid, 250 mL * 2 washed twice, 250 mL purified water are washed once, and organic layer is with more than an amount of anhydrous sodium sulfate drying 4h.Suction filtration, filter cake be with exsiccant toluene 50 mL * 3 washing three times, the filtrating of collecting is evaporated in 65 ± 2 ℃/0.08 ~ 0.10 Mpa dried, fully behind the evaporate to dryness yellow oil.The sampling censorship, performance liquid (HPLC) check purity reaches 99.9%.
Embodiment 2, are the method that the Al catalysts of part prepares Propofol with reactant 2-isopropyl-phenol, and step is following, ⑴. under 200 ~ 210 ℃ of temperature, prepare catalyzer 2-isopropyl-phenol aluminium with 2-isopropyl-phenol and aluminium powder; ⑵. solvent toluene dewaters through the sodium drying; ⑶. in solvent toluene, raw material propylene and 2-isopropyl-phenol, in the presence of catalyzer 2-isopropyl-phenol aluminium, synthetic Propofol.Wherein, 2-isopropyl-phenol purity should be higher than 99%.Temperature of reaction is 90 ~ 100 ℃, and pressure is about 1.5 ~ 2.0 Mpa, and the reaction times is about 3h.Propylene: 2-isopropyl-phenol: 2-isopropyl-phenol aluminium: the mass volume ratio=1:0.6:0.1:43 of toluene.
Embodiment 3, are the method that the Al catalysts of part prepares Propofol with reactant 2-isopropyl-phenol, and step is following, ⑴. under 200 ~ 210 ℃ of temperature, prepare catalyzer 2-isopropyl-phenol aluminium with 2-isopropyl-phenol and aluminium powder; ⑵. solvent benzol dewaters through the sodium drying; ⑶. in solvent benzol, raw material propylene and 2-isopropyl-phenol, in the presence of catalyzer 2-isopropyl-phenol aluminium, synthetic Propofol.Wherein, 2-isopropyl-phenol purity should be higher than 99%.Temperature of reaction is 70 ~ 90 ℃, and pressure is about 2.0 ~ 3.0 Mpa, and the reaction times is about 4h.Propylene: 2-isopropyl-phenol: 2-isopropyl-phenol aluminium: the mass volume ratio=1:0.5:0.09:42 of benzene.
Embodiment 4, are the method that the Al catalysts of part prepares Propofol with reactant 2-isopropyl-phenol, and step is following, ⑴. under 200 ~ 210 ℃ of temperature, prepare catalyzer 2-isopropyl-phenol aluminium with 2-isopropyl-phenol and aluminium powder; ⑵. solvent xylene dewaters through the sodium drying; ⑶. in solvent xylene, raw material propylene and 2-isopropyl-phenol, in the presence of catalyzer 2-isopropyl-phenol aluminium, synthetic Propofol.Wherein, 2-isopropyl-phenol purity should be higher than 99%.Temperature of reaction is 120 ~ 140 ℃, and pressure is about 0.5 ~ 0.6 Mpa, and the reaction times is about 4h.Propylene: 2-isopropyl-phenol: 2-isopropyl-phenol aluminium: the mass volume ratio=1:0.5:0.11:43 of YLENE.
Embodiment 5, and is basic identical with embodiment 1, but following change is arranged: the temperature of reaction of said step ⑶ is 120 ~ 140 ℃, and pressure is about 0.5 ~ 0.6 Mpa, and the reaction times is about 0.5 h.Propylene: 2-isopropyl-phenol: 2-isopropyl-phenol aluminium: the mass volume ratio=1:0.7:0.11:44 of solvent.
Embodiment 6, and is basic identical with embodiment 1, but following change is arranged: propylene among the said step ⑶: 2-isopropyl-phenol: 2-isopropyl-phenol aluminium: the mass volume ratio=1:0.5:0.11:43 of solvent.
Claims (8)
1. one kind is the method that the Al catalysts of part prepares Propofol with reactant 2-isopropyl-phenol, it is characterized in that step is following,
⑴. prepare catalyzer 2-isopropyl-phenol aluminium with 2-isopropyl-phenol and aluminium powder;
⑵. solvent dewaters through the sodium drying;
⑶. in solvent, raw material propylene and 2-isopropyl-phenol, in the presence of catalyzer 2-isopropyl-phenol aluminium, synthetic Propofol.
2. according to claim 1 is the method that the Al catalysts of part prepares Propofol with reactant 2-isopropyl-phenol, it is characterized in that the described preparation catalyzer of step ⑴ is to adopt 200 ~ 210 ℃ temperature of reaction.
3. according to claim 1 is the method that the Al catalysts of part prepares Propofol with reactant 2-isopropyl-phenol; It is characterized in that, said step ⑶, the temperature of reaction of synthetic Propofol is 70 ~ 140 ℃; Pressure is about 0.5 ~ 3.0 Mpa, and the reaction times is about 0.5 ~ 4h.
4. according to claim 1 is the method that the Al catalysts of part prepares Propofol with reactant 2-isopropyl-phenol, it is characterized in that among the said step ⑶, 2-isopropyl-phenol purity is higher than 99%.
5. according to claim 1 is the method that the Al catalysts of part prepares Propofol with reactant 2-isopropyl-phenol, it is characterized in that among the said step ⑶, temperature of reaction is 90 ~ 100 ℃, and pressure is about 1.5 ~ 2.0 Mpa, and the reaction times is about 3h.
6. described according to one of claim 1 ~ 5 is the method that the Al catalysts of part prepares Propofol with reactant 2-isopropyl-phenol; It is characterized in that; Among the said step ⑶, propylene: 2-isopropyl-phenol: 2-isopropyl-phenol aluminium: the mass volume ratio=1:0.5 of solvent ~ 0.7:0.09 ~ 0.11:42 ~ 44.
7. according to claim 6 is the method that the Al catalysts of part prepares Propofol with reactant 2-isopropyl-phenol; It is characterized in that; Among the said step ⑶, propylene: 2-isopropyl-phenol: 2-isopropyl-phenol aluminium: the mass volume ratio=1:0.6:0.1:43 of solvent.
8. according to claim 7 is the method that the Al catalysts of part prepares Propofol with reactant 2-isopropyl-phenol, it is characterized in that the solvent of said step ⑵ and step ⑶ adopts toluene.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011103689578A CN102503776A (en) | 2011-11-18 | 2011-11-18 | Method for synthesizing propofol by utilizing aluminum catalyst taking reactant 2-isopropyl phenol as ligand |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011103689578A CN102503776A (en) | 2011-11-18 | 2011-11-18 | Method for synthesizing propofol by utilizing aluminum catalyst taking reactant 2-isopropyl phenol as ligand |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102503776A true CN102503776A (en) | 2012-06-20 |
Family
ID=46215927
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2011103689578A Pending CN102503776A (en) | 2011-11-18 | 2011-11-18 | Method for synthesizing propofol by utilizing aluminum catalyst taking reactant 2-isopropyl phenol as ligand |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102503776A (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3271314A (en) * | 1958-12-04 | 1966-09-06 | Ethyl Corp | 2, 6-diisopropylphenol |
| US4870215A (en) * | 1988-06-24 | 1989-09-26 | Ethyl Corporation | Phenol alkylation process |
| JPH07223985A (en) * | 1994-02-10 | 1995-08-22 | Goi Kasei Kk | 2-methyl-6-t-amylphenol |
| CN101538191A (en) * | 2009-05-06 | 2009-09-23 | 西安力邦制药有限公司 | Synthetic method of high-purity propofol |
-
2011
- 2011-11-18 CN CN2011103689578A patent/CN102503776A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3271314A (en) * | 1958-12-04 | 1966-09-06 | Ethyl Corp | 2, 6-diisopropylphenol |
| US4870215A (en) * | 1988-06-24 | 1989-09-26 | Ethyl Corporation | Phenol alkylation process |
| JPH07223985A (en) * | 1994-02-10 | 1995-08-22 | Goi Kasei Kk | 2-methyl-6-t-amylphenol |
| CN101538191A (en) * | 2009-05-06 | 2009-09-23 | 西安力邦制药有限公司 | Synthetic method of high-purity propofol |
Non-Patent Citations (1)
| Title |
|---|
| 罗明耀等: "2,6-二异丙基苯酚的合成研究", 《浙江工学院学报》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2910540B1 (en) | Novel ruthenium complex and method for preparing methanol and diol | |
| Zhang et al. | Nano‐CuO‐Catalyzed Ullmann Coupling of Phenols with Aryl Halides under Ligand‐Free Conditions | |
| EP2579986A1 (en) | Carboxylation catalysts | |
| CN104628548A (en) | Method for preparing acetophenone by bionic catalytic oxidation of ethylbenzene | |
| Mba et al. | Ti (IV)-amino triphenolate complexes as effective catalysts for sulfoxidation | |
| CN101538191B (en) | Synthetic method of high-purity propofol | |
| CN105503842A (en) | Method for preparing nebivolol hydrochloride epoxy intermediate 6-fluoro-2-epoxy ethyl chroman | |
| CN103012268B (en) | Novel preparation method for ivabradine | |
| CN102643237A (en) | Method for preparing 1H-imidazole-4-formic acid | |
| CN102503776A (en) | Method for synthesizing propofol by utilizing aluminum catalyst taking reactant 2-isopropyl phenol as ligand | |
| CN102180811B (en) | Method for preparing closantel sodium intermediate by catalytic hydrogenation | |
| Liu et al. | A novel micro-emulsion catalytic system for highly selective hydroxylation of benzene to phenol with hydrogen peroxide | |
| CN103880573A (en) | Preparation method for biphenyl-type compound | |
| CN103232324A (en) | Method for preparing (R)-3,5-bis(trifluoromethyl)benzene-ethanol | |
| CN103333129B (en) | One prepares the method for the 4-amino-6-tertiary butyl-3-methylthio group-1,2,4-triazine-5 (4H)-one | |
| CN103333130B (en) | The preparation method of the 4-amino-6-tertiary butyl-3-methylthio group-1,2,4-triazine-5 (4H)-one | |
| CN102633680A (en) | Catalyst for preparing 3,3-diethoxyl propionitrile and preparation method of catalyst | |
| CN106699523A (en) | Synthetic method of o-phenyl phenoxyethanol | |
| CN101684069B (en) | Method for enriching acetol from biomass pyrolysis liquid aqueous phase system | |
| US20120165532A1 (en) | One-Step Synthesis Method of 2,9-Dimethyl-4,7-Diphenyl-1,10- Phenanthroline | |
| CN108273523A (en) | A kind of production method of anticoagulation medicine intermediate | |
| CN113117753B (en) | Hydrophobic catalyst, preparation method thereof and preparation method of beta-ionone | |
| CN103626622B (en) | Method for preparing methyl cyclopentadiene dimer | |
| CN111302880B (en) | Application of iron catalyst in reduction coupling reaction and preparation method of aromatic ring and heterocyclic derivative | |
| CN102964317B (en) | New preparation method of tetrasubstituted furan compound |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20120620 |