CN1455775A - Method for preparing Dl-alpha-to copherol with high yield - Google Patents
Method for preparing Dl-alpha-to copherol with high yield Download PDFInfo
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- CN1455775A CN1455775A CN00819974.4A CN00819974A CN1455775A CN 1455775 A CN1455775 A CN 1455775A CN 00819974 A CN00819974 A CN 00819974A CN 1455775 A CN1455775 A CN 1455775A
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- alpha
- tocopherol
- silica
- alumina
- isophytol
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Abstract
Disclosed is a method for preparing Dl-alpha-tocopherol with a high yield through the condensation of isophytol or phytol derivatives with trimethylhydroquinone (TMHQ) in the presence of a Zn-Al heterogeneous catalyst system. At 80 to 120 deg.C, the condensation is carried out for 2 to 7 hours in the presence of a Zn(II) ion-coated alumina-silica catalyst in an n-heptane solvent. The synthetic Zn(II) ion-coated silica-alumina synthetic catalyst system can remarkably reduce side-reactions upon the condensation of isophytol or phytol derivatives and TMHQ, thus producing DL-alpha-tocopherol with a high purity at a high yield. In addition, the catalyst system is greatly convenient to handle and therefore apply for continuous reactions for the preparation of DL-alpha-tocopherol.
Description
Technical field
The present invention relates to a kind of method of the DL-of preparation alpha-tocopherol, this method is included under the existence of Zn-Al allos catalyzer and makes isophytol or phytol derivative and Trimethylhydroquinone (TMHQ) condensation.More specifically, the present invention relates to the silica-alumina synthetic catalyst that a kind of bag has been coated with Zn (II), this catalyzer is by the grappling simultaneously of Zn site and Al site, thereby very effective aspect produced in high yields DL-alpha-tocopherol.
Prior art
In the past few decades, made huge effort aspect the DL-alpha-tocopherol using Zn (II) ion effectively to prepare as metal catalyst (lewis acid catalyst).Usually, the condensation by isophytol and Trimethylhydroquinone (TMHQ) prepares the DL-alpha-tocopherol, and its reaction is as follows:
For example, United States Patent (USP) 4217285 (patent hereinafter referred to as ' 285) discloses in the presence of acid (especially HCl), uses ZnCl in toluene or normal hexane solvent
2And the DL-alpha-tocopherol that carries out of silica-alumina (or silicon-dioxide-gel) is synthetic, claim can 95-96% purity, 99% or higher productive rate make tocopherol.Simultaneously, two United States Patent (USP)s 4634781 and 7639533 that transfer BASF disclose the method for producing the DL-alpha-tocopherol, wherein at ZnCl
2Under the existence of HCl, isophytol and amine such as tridecyl amine are reacted, with the TNHQ reaction, these methods have comparatively complexity and poor efficiency then.In these examples, it is said can 94-95% purity and the productive rate of 95-98% make tocopherol.
But conventional technology improves the leeway of purity in addition, is 95% because adopt the average purity of the DL-alpha-tocopherol that these technology make low.Particularly, the patent of BASF is inefficient, and reason is that these methods can not satisfy the required productive rate of production DL-alpha-tocopherol.
In ' 285 patents, toluene or hexane are as solvent, but they make the overall yield of DL-alpha-tocopherol very poor.When using toluene, toluene self has part and isophytol reaction, generates unwanted by product.Though hexane with isophytol reaction, owing to the cause of its boiling point low (about 69 ℃) has prolonged the time of reacting, thus the time catalyzer aggravated the dehydration of isophytol.In addition, when DL-alpha-tocopherol synthetic is when carrying out with such step, can obtain the relatively large structure by product similar, thereby reduce the purity of DL-alpha-tocopherol to the DL-alpha-tocopherol.When using acid or alkali to make co-catalyst, more like this.Using ZnCl separately
2But not with catalyzer such as AlCl based on Al
3Or SiO
2-Al
2O
3In the example of Shi Yonging, similarly the amount of by product is also very big together.In addition, Chang Gui technology also is subjected to handling because of using the puzzlement of this severe problem of waste water that acid or alkali (example hydrochloric acid) produces.
Disclosure of an invention
Revised and adjusted according to the knowledge of catalyzed reaction mechanism, thereby caused the present invention.
The present inventor has carried out extensive and deep research to the preparation of DL-alpha-tocopherol, found that, by sintering with ZnCl
2Bag is coated on the silica-alumina and obtains a kind of catalyst system of novelty, can be used to easily with the highly purified DL-alpha-tocopherol of produced in high yields.
ZnCl
2Obtain using blended ZnCl with the effectiveness of silica-alumina
2And AlCl
3The support of various tests of catalyst system, the result of these tests vital role that to be Zn (II) ions play in DL-alpha-tocopherol synthetic as catalyzer, Al (III) ion is then as cocatalyst, reduced side reaction and increased the purity of final product.Generally speaking, found to use Zn-Al mixed catalyst system to obtain pure DL-alpha-tocopherol with high yield.
Based on these discoveries, the present inventor becomes catalyst system based on Zn-Al with the system development of Zn (II) ionic catalyst, synthesizes the site for the DL-alpha-tocopherol provides ideal.After carrying out a large amount of tests, find that it is the most effective preparing the DL-alpha-tocopherol with the silica-alumina catalyzer that Zn (II) ion packet is coated with from very a spot of isophytol or phytol derivative, and do not have by product to produce basically.
Therefore, an object of the present invention is to provide a kind of easily with the method for produced in high yields DL-alpha-tocopherol.
Another object of the present invention provides a kind of method of the DL-of preparation alpha-tocopherol, and this method can be used for the successive reaction with commercial mass production DL-alpha-tocopherol very expediently.
Another purpose of the present invention provides a kind of method of the DL-of preparation alpha-tocopherol, and this method does not produce by product basically, therefore can amount seldom use expensive isophytol or phytol derivative.
According to the present invention, by a kind of method with produced in high yields DL-alpha-tocopherol is provided, can realize above-mentioned purpose, described method is included in 80-120 ℃, bag be coated with Zn (II) ionic silica-alumina catalyst system in the presence of, in hydrocarbon solvent (especially Skellysolve A solvent), make isophytol or phytol derivative and Trimethylhydroquinone condensation 2-7 hour.
Preferred forms of the present invention
According to the present invention, by making isophytol or phytol derivative and TMHQ in non-polar solvent, bag be coated with Zn (II) ionic silica-alumina allos catalyzer in the presence of condensation and make the DL-alpha-tocopherol.
Be used for isophytol of the present invention or the phytol derivative is represented by following formula I or II:
In the formula, X and Y independently are hydroxyl, halogen atom or acetoxyl.
Basically, mixed catalyst of the prior art system is subjected to by the puzzlement of using into the problem that divided catalyst causes respectively.In addition, they and be not easy to the operation.Owing to there are these shortcomings, conventional mixed catalyst system quite is difficult to use in the continuous preparation method of DL-alpha-tocopherol.But the catalyst system that uses Zn of the present invention (II) bag to be coated in silica-alumina can overcome the problem that exists in the conventional catalyst system.Appropriate catalyst of the present invention is made into Zn (II) and is supported on form on the silica-alumina, and this catalyzer has the site of grappling Zn (II) and Al (III) simultaneously like this.By with ZnCl
2Inject silica-alumina carriers,, thereby Zn (II) ion packet is coated on the silica-alumina carriers then about 400 ℃ of sintering 2 hours.For example, at ZnCl
2Use and carry out behind the sintering and in the catalyst system that obtains with the amount of silica-alumina 50 weight %, the result of its compositional analysis is as shown in the table 1, and these results prove, ZnCl
2Successfully be impregnated in this silica-alumina carriers.
Table 1
| Composition | Si | ?Al | ?Zn | ?Cl |
| Weight % | 21.6 | ?12.6 | ?17.9 | ?12.7 |
When preparation DL-alpha-tocopherol in the presence of this catalyzer, find the product of gained and have ZnCl respectively
2The product of gained is the same good during with silica-alumina, even better.This finds to have proved without doubt that catalyzer of the present invention provides the ability of the ecotopia of preparation DL-alpha-tocopherol.
When using 20-450 weight part catalyzer of the present invention, per 100 weight part TMHQ can obtain preferable result.When preparation DL-alpha-tocopherol, the catalyzer of 100-200 weight part scope can obtain better result.When preparation catalyzer of the present invention, be preferably the ZnCl that per 100 weight part silica-aluminas use the 5-250 weight part
2, the best is that 100 weight part silica-aluminas use 20-80 weight part ZnCl
2According to catalytically effective amount, when the amount of catalyzer with respect to TMHQ remains in the specific scope, and work as ZnCl
2With SiO
2-Al
2O
3The ratio of amount when maintaining such scope, can obtain excellent copherol products.
Be used for examples of solvents of the present invention and comprise aromatic solvent, as toluene, benzene and dimethylbenzene, and saturated hydrocarbon solvent such as Skellysolve A, normal hexane and the octane of aliphatic series, preferred toluene and Skellysolve A.In these solvents, Skellysolve A can guarantee that the present invention obtains best synthetic result.
Best reaction time range is 2-7 hour, and the suitable reaction temperature scope is 80-120 ℃.
Following table 2 has provided reaction conditions and result.
Table 2
Prepare the DL-alpha-tocopherol according to following reaction conditions
| Catalyzer | Solvent | Temperature of reaction (℃) | Reaction times (hour) | Productive rate (%) | Purity (%) |
| ZnCl 2-Si-Al | Toluene | 110 | ?3 | ?93.4 | ?99.4 |
| Bag has been coated with ZnCl 2Si-Al | Skellysolve A | 99 | ?4 | ?99.4 | ?99.1 |
| Bag has been coated with ZnCl 2Si-Al | Toluene | 110 | ?3 | ?93.3 | ?99.1 |
Adopt vapor-phase chromatography (HP-5890 series), with all reaction product of HP-1 chromatogram column analysis.
That summed up in the table 2 is the result that TMHQ and the isophytol of equivalent reacts with different catalyzer in solvent separately.Can find out obviously that from table 2 product that the Si-Al catalyzer that uses bag to be coated with Zn (II) is obtained uses no better than and use ZnCl in same solvent
2The product that catalyst mixture obtained with Si-Al.When using toluene, from the productive rate of 93-94% as can be known, about 6% TMHQ does not react.Therefore, the respective amount of isophytol is not participated in reaction yet, and finds that this part is by this catalyst decomposes.On the other hand, Skellysolve A brings up at least 99% with productive rate, and the amount that makes unreacted TMHQ is 1% or still less level.Therefore, 99% or more isophytol participated in reaction, and its corresponding amount, promptly 1% or isophytol still less by catalyst decomposes.This result shows, isophytol in pentane than more stable in other solvent.The result is, uses pentane can produce the required raw materials cost of DL-alpha-tocopherol thereby reduce with reducing to minimum with the amount of the required isophytol of the TMHQ complete reaction of specified rate as reaction solvent.
According to following embodiment, can better understand the present invention, these embodiment are illustrative, and unrestricted the present invention.
Comparative example 1
Brush the round-bottomed flask of the 100ml that is equipped with Dean-Stark device and condenser with nitrogen, afterwards, with the TMHQ of 3g and the ZnCl of 1g
2Be added in this flask, add the toluene of 50ml then, stir this solution.After being added to the 2g silica-alumina in this solution,, simultaneously nitrogen is blown in the flask this flask fit on dropping funnel.The solution of 6g isophytol in 10ml toluene is added in this dropping funnel this flask of reflux in nitrogen atmosphere.When refluxing, the toluene solution with isophytol in 2 hours time slowly is added in this flask.After adding fully, refluxed again 1 hour.Adopt GC assay products mixture, find that the transformation efficiency of TMHQ is 93%, the purity of DL-alpha-tocopherol is 99% or higher.
Preparation example
Bag has been coated with the silica-alumina Preparation of catalysts of Zn (II)
At 15g H
2The ZnCl of dissolving 15g in the mixed solution of O and 3g, 35% the HCl aqueous solution
2, add the 30g silica-alumina then.For with ZnCl
2Be impregnated in this silica-alumina, the excessive precipitation that obtains, dry then, 400 ℃ of sintering 2 hours, obtain the silica-alumina catalyzer that bag has been coated with Zn (II).
Embodiment 1
Under the reaction conditions identical with comparative example 1, the catalyzer that 3g TMHQ and 4g are made according to preparation example is added in the flask, and the Skellysolve A that adds 50ml then is as solvent.When refluxing, in nitrogen atmosphere, slowly add the solution of 6g isophytol in Skellysolve A.After all adding, continue to reflux more than 2 hour.Adopt GC assay products mixture, find that the transformation efficiency of TMHQ is 99% or higher, the purity of DL-alpha-tocopherol is 99% or higher.
As described earlier in this article, the silica-alumina catalyst system that bag of the present invention has been coated with Zn (II) is compared with the conventional catalyst that is used to prepare the DL-alpha-tocopherol, significantly reduced the side reaction after isophytol and the TMHQ condensation, thereby can produce the DL-alpha-tocopherol with the high purity high yield.In addition, catalyst system of the present invention is in operating aspect and be used to prepare and also improved greatly aspect the successive reaction of DL-alpha-tocopherol.Owing to have these advantages, the silica-alumina catalyzer that bag of the present invention has been coated with Zn (II) can be used for producing highly purified DL-alpha-tocopherol with commercial size with high yield effectively.
Described the present invention in the mode of setting forth, should be understood that employed term only is to set forth character, and nonrestrictive.According to above-mentioned disclosure, can make many modifications and change to the present invention.Therefore, should be understood that within the scope of incidental claims that the present invention can specifically describe embodied in other in addition by this paper.
Claims (7)
1. method with produced in high yields D1-alpha-tocopherol, it is characterized in that, this method is included in 80-120 ℃, bag be coated with Zn (II) ionic silica-alumina catalyzer in the presence of, in the Skellysolve A solvent, make isophytol or phytol derivative and Trimethylhydroquinone condensation 2-7 hour.
2. the method for claim 1 is characterized in that, with ZnCl
2Mix in the silica-alumina carriers, mixed ZnCl at 400 ℃ of sintering then
2Carrier 2 hours, obtain described bag and be coated with Zn (II) ionic silica-alumina.
3. method as claimed in claim 2 is characterized in that, the silica-alumina carriers of per 100 weight parts is used the ZnCl of 5-250 weight part
2
4. method as claimed in claim 2 is characterized in that, the silica-alumina carriers of per 100 weight parts is used the ZnCl of 20-80 weight part
2
5. the method for claim 1 is characterized in that, described isophytol or phytol derivative are represented by following Formula I or II:
In the formula, X and Y independently are hydroxyl, halogen atom or acetoxyl.
6. the method for claim 1 is characterized in that, the Trimethylhydroquinone of per 100 weight parts uses the described catalyzer of 20-450 weight part.
7. the method for claim 1 is characterized in that, the Trimethylhydroquinone of per 100 weight parts uses the described catalyzer of 100-200 weight part.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/KR2000/001201 WO2002034738A1 (en) | 2000-10-23 | 2000-10-23 | Method for preparing dl-alpha-tocopherol with high yield |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1455775A true CN1455775A (en) | 2003-11-12 |
| CN1186337C CN1186337C (en) | 2005-01-26 |
Family
ID=27606949
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB008199744A Expired - Fee Related CN1186337C (en) | 2000-10-23 | 2000-10-23 | Method for preparing Dl-alpha-to copherol with high yield |
Country Status (3)
| Country | Link |
|---|---|
| EP (1) | EP1334093A4 (en) |
| JP (1) | JP2004512332A (en) |
| CN (1) | CN1186337C (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103396392A (en) * | 2013-08-10 | 2013-11-20 | 吉林北沙制药有限公司 | Environmentally-friendly synthesis method of vitamin E |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5622868B2 (en) * | 1972-08-30 | 1981-05-27 | ||
| JPS6019309B2 (en) * | 1976-09-29 | 1985-05-15 | 日清製粉株式会社 | Production method of high purity dl-α-tocopherol |
| JPS607993B2 (en) * | 1978-01-12 | 1985-02-28 | 株式会社クラレ | Method for producing dl-α-tocopherol |
| JPS59190987A (en) * | 1983-04-11 | 1984-10-29 | Mitsui Toatsu Chem Inc | Preparation of dl-alpha-tocopherol |
| JP3416281B2 (en) * | 1994-04-12 | 2003-06-16 | エーザイ株式会社 | Method for producing α-tocopherol derivative and catalyst |
| US6005122A (en) * | 1996-12-23 | 1999-12-21 | Basf Aktiengesellschaft | Preparation of α-tocopherol or α-tocopheryl acetate by reacting trimethylhydroquinone and phytol or isophytol, with recycling of the zinc halide condensation catalyst |
| FR2784104B1 (en) * | 1998-09-18 | 2002-12-27 | Rhone Poulenc Nutrition Animal | PROCESS FOR THE PREPARATION OF VITAMIN E |
-
2000
- 2000-10-23 JP JP2002537729A patent/JP2004512332A/en active Pending
- 2000-10-23 EP EP00971854A patent/EP1334093A4/en not_active Withdrawn
- 2000-10-23 CN CNB008199744A patent/CN1186337C/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103396392A (en) * | 2013-08-10 | 2013-11-20 | 吉林北沙制药有限公司 | Environmentally-friendly synthesis method of vitamin E |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1334093A1 (en) | 2003-08-13 |
| EP1334093A4 (en) | 2004-02-04 |
| JP2004512332A (en) | 2004-04-22 |
| CN1186337C (en) | 2005-01-26 |
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Granted publication date: 20050126 Termination date: 20091123 |