JPS62226976A - Production of dl-alpha-tocopherol - Google Patents
Production of dl-alpha-tocopherolInfo
- Publication number
- JPS62226976A JPS62226976A JP61070553A JP7055386A JPS62226976A JP S62226976 A JPS62226976 A JP S62226976A JP 61070553 A JP61070553 A JP 61070553A JP 7055386 A JP7055386 A JP 7055386A JP S62226976 A JPS62226976 A JP S62226976A
- Authority
- JP
- Japan
- Prior art keywords
- tocopherol
- reducing agent
- metallic zinc
- producing
- benzoquinone
- 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.)
- Granted
Links
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 title claims abstract description 16
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 11
- 229960000984 tocofersolan Drugs 0.000 title claims description 15
- 235000001815 DL-alpha-tocopherol Nutrition 0.000 title claims description 12
- 239000011627 DL-alpha-tocopherol Substances 0.000 title claims description 12
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 title claims description 11
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims abstract description 22
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract description 21
- 229910052725 zinc Inorganic materials 0.000 claims abstract description 20
- 239000011701 zinc Substances 0.000 claims abstract description 20
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 17
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims abstract description 14
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims abstract description 12
- 239000003638 chemical reducing agent Substances 0.000 claims abstract description 11
- 238000006243 chemical reaction Methods 0.000 claims abstract description 10
- 238000006482 condensation reaction Methods 0.000 claims abstract description 10
- BOTWFXYSPFMFNR-PYDDKJGSSA-N phytol Chemical compound CC(C)CCC[C@@H](C)CCC[C@@H](C)CCC\C(C)=C\CO BOTWFXYSPFMFNR-PYDDKJGSSA-N 0.000 claims abstract description 9
- 239000003054 catalyst Substances 0.000 claims abstract description 7
- 235000005074 zinc chloride Nutrition 0.000 claims abstract description 6
- 239000011592 zinc chloride Substances 0.000 claims abstract description 6
- AUFZRCJENRSRLY-UHFFFAOYSA-N 2,3,5-trimethylhydroquinone Chemical compound CC1=CC(O)=C(C)C(C)=C1O AUFZRCJENRSRLY-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000007858 starting material Substances 0.000 claims description 10
- 229910052751 metal Inorganic materials 0.000 claims description 8
- 239000002184 metal Substances 0.000 claims description 8
- RWSOTUBLDIXVET-UHFFFAOYSA-M hydrosulfide Chemical compound [SH-] RWSOTUBLDIXVET-UHFFFAOYSA-M 0.000 claims description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 abstract description 25
- QIXDHVDGPXBRRD-UHFFFAOYSA-N 2,3,5-trimethylcyclohexa-2,5-diene-1,4-dione Chemical compound CC1=CC(=O)C(C)=C(C)C1=O QIXDHVDGPXBRRD-UHFFFAOYSA-N 0.000 abstract description 13
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 abstract description 6
- 239000001707 (E,7R,11R)-3,7,11,15-tetramethylhexadec-2-en-1-ol Substances 0.000 abstract description 4
- BLUHKGOSFDHHGX-UHFFFAOYSA-N Phytol Natural products CC(C)CCCC(C)CCCC(C)CCCC(C)C=CO BLUHKGOSFDHHGX-UHFFFAOYSA-N 0.000 abstract description 4
- HNZBNQYXWOLKBA-UHFFFAOYSA-N Tetrahydrofarnesol Natural products CC(C)CCCC(C)CCCC(C)=CCO HNZBNQYXWOLKBA-UHFFFAOYSA-N 0.000 abstract description 4
- BOTWFXYSPFMFNR-OALUTQOASA-N all-rac-phytol Natural products CC(C)CCC[C@H](C)CCC[C@H](C)CCCC(C)=CCO BOTWFXYSPFMFNR-OALUTQOASA-N 0.000 abstract description 4
- 239000003814 drug Substances 0.000 abstract description 3
- 230000000694 effects Effects 0.000 abstract description 3
- 239000002904 solvent Substances 0.000 abstract description 3
- 229930003427 Vitamin E Natural products 0.000 abstract description 2
- 235000013305 food Nutrition 0.000 abstract description 2
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- 229940046009 vitamin E Drugs 0.000 abstract description 2
- 235000019165 vitamin E Nutrition 0.000 abstract description 2
- 239000011709 vitamin E Substances 0.000 abstract description 2
- 150000001875 compounds Chemical class 0.000 abstract 2
- GRWZHXKQBITJKP-UHFFFAOYSA-L dithionite(2-) Chemical compound [O-]S(=O)S([O-])=O GRWZHXKQBITJKP-UHFFFAOYSA-L 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- 238000000926 separation method Methods 0.000 abstract 1
- 229940042585 tocopherol acetate Drugs 0.000 description 19
- 238000000034 method Methods 0.000 description 12
- 229940087168 alpha tocopherol Drugs 0.000 description 8
- 239000002076 α-tocopherol Substances 0.000 description 8
- 238000006722 reduction reaction Methods 0.000 description 7
- 238000000199 molecular distillation Methods 0.000 description 6
- KEVYVLWNCKMXJX-ZCNNSNEGSA-N Isophytol Natural products CC(C)CCC[C@H](C)CCC[C@@H](C)CCC[C@@](C)(O)C=C KEVYVLWNCKMXJX-ZCNNSNEGSA-N 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 238000007796 conventional method Methods 0.000 description 4
- 239000002002 slurry Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 description 3
- ZAKOWWREFLAJOT-UHFFFAOYSA-N d-alpha-Tocopheryl acetate Natural products CC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-UHFFFAOYSA-N 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 2
- 229940011051 isopropyl acetate Drugs 0.000 description 2
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 235000004835 α-tocopherol Nutrition 0.000 description 2
- 229940005561 1,4-benzoquinone Drugs 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229940093499 ethyl acetate Drugs 0.000 description 1
- 238000004880 explosion Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 1
- 229940090181 propyl acetate Drugs 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- DGQOCLATAPFASR-UHFFFAOYSA-N tetrahydroxy-1,4-benzoquinone Chemical compound OC1=C(O)C(=O)C(O)=C(O)C1=O DGQOCLATAPFASR-UHFFFAOYSA-N 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
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
- Pyrane Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は、医薬品、食品、動物薬、飼料などに有用なａ
−α−トコフェロールの新規な製造方法に関する。[Detailed Description of the Invention] [Industrial Application Field] The present invention provides an a.
-Regarding a novel method for producing α-tocopherol.
ａ−α−トコフェロールは、代表的なビタミンＥであり
、医薬品、食品、動物薬、飼料などとして広く汎用され
ており、需要が年々増大している。α-α-Tocopherol is a typical vitamin E and is widely used as medicine, food, animal medicine, feed, etc., and its demand is increasing year by year.
このａ−α−トコフェロールを製造する方法としては、
従来より数多く知られている。The method for producing this a-α-tocopherol is as follows:
Many of them are known from the past.
これらの方法のほとんどは、２．３．５− トリメチル
ハイドロキノンと、フィトール、イソフィトールなどの
フィトール類を種々の触媒を用いて、縮合反応するもの
である（例えば特開昭４７−２９３６６、特開昭４９−
４７３７２、特開昭４８−４８４１２、特公昭４５−２
１８３５など）。Most of these methods involve a condensation reaction between 2,3,5-trimethylhydroquinone and phytols such as phytol and isophytol using various catalysts (for example, JP-A No. 47-29366, JP-A No. Showa 49-
47372, Japanese Patent Publication No. 48-48412, Special Publication No. 45-2
1835 etc.).
しかしながら、この２，３．５−トリメチルハイドロキ
ノンを出発物質とする方法は、工業的には次のような欠
点を有している。However, this method using 2,3.5-trimethylhydroquinone as a starting material has the following drawbacks from an industrial perspective.
即ち、■２，３．５−）リメチルハイドロキノンは飛散
しやすい粉末で、皮膚に付着すると炎症を起こし易い、
■帯電し易く、静電気による爆発を誘発し易いため、取
り扱い上特別の対策が必要とされる、■空気中にて酸化
を受けやすく、その結果、この酸化物はａ−α−トコフ
ェロールの純度に悪影響を及ぼす、及び■２，３．５−
）リメチルハイドロキノンを結晶として取り出すため
には濾過、乾燥などの操作が必要であり、工業的には不
利である、という種々の欠点を有する。In other words, 2,3.5-)limethylhydroquinone is a powder that easily scatters and can easily cause inflammation if it comes into contact with the skin.
■Easily charged and prone to explosion due to static electricity, requiring special handling precautions; ■Easy to oxidize in the air, and as a result, this oxide reduces the purity of a-α-tocopherol. have an adverse effect, and ■2, 3.5-
) Limethylhydroquinone has various drawbacks such as requiring operations such as filtration and drying in order to extract it as crystals, which is disadvantageous from an industrial perspective.
そこで、これらの欠点を解決するために、２゜３．５−
）リメチルハイドロキノンを出発物質とせず、２，３．
５−）ツメチル−１，４−ベンゾキノンを出発物質とす
る方法も提案されている（特開昭５０−１５７３６７、
特開昭５０−１５７３６８、特開昭５０−１５７３６９
＞。Therefore, in order to solve these drawbacks, 2゜3.5-
2,3.) without using remethylhydroquinone as a starting material.
A method using 5-)trimethyl-1,4-benzoquinone as a starting material has also been proposed (JP-A-50-157367,
JP-A-50-157368, JP-A-50-157369
>.
これらの方法は、２，３．５−トリメチル−１，４＝ベ
ンゾキノンを出発物質とし、還元触媒の存在下、接触水
素添加還元法により、２，３．５− ）リメチルハイド
ロキノンを得る方法であるが、これらの方法は数ｋｇ／
ｃｍ２の水素ガスを使用するため、安全性の確保に特別
の対応策が必要とされ、工業的には問題が多い。即ち、
工業化のためには、耐圧装置、安全装置などが必要であ
り、経済的な見地から極めて不利である。In these methods, 2,3.5-trimethyl-1,4=benzoquinone is used as a starting material and 2,3.5-)limethylhydroquinone is obtained by a catalytic hydrogenation reduction method in the presence of a reduction catalyst. However, these methods are suitable for several kg/
Since hydrogen gas of cm2 is used, special measures are required to ensure safety, which poses many problems from an industrial perspective. That is,
For industrialization, pressure-resistant equipment, safety equipment, etc. are required, which is extremely disadvantageous from an economic standpoint.
そこで本発明者等は、２．３．５−トリメチル−１，４
−ベンゾキノンを出発原料としてｄｌ−トコフェロール
を製造する従来の方法の欠点を改良し、高純度、高収率
のｄｌ−トコフェロールを製造する方法について長年検
討を重ねてきたが、次の方法が所期の目的を満足するこ
とができることを見出し、本発明を完成するに到った。Therefore, the present inventors proposed 2.3.5-trimethyl-1,4
-We have been studying for many years how to improve the shortcomings of the conventional method of producing dl-tocopherol using benzoquinone as a starting material and produce dl-tocopherol with high purity and high yield. The present invention has been completed based on the discovery that the above objectives can be satisfied.
本発明の方法は、〃−α−トコフェロールを製造するに
際し、２．３．５−１−ツメチル−１，４−ベンゾキノ
ンを出発物質とし、これを還元剤を用いて還元して、２
．３．５− ）リメチルハイドロキノンとし、次いで得
られた２、３．．５− ）リメチルハイドロキノン体を
反応液から取りだすことなく、該液にフィトール類を加
え、触媒として金属亜鉛及び塩化亜鉛を用いて縮合反応
せしめることを特徴とする〃−α−トコフェロールの製
造方法である。In the method of the present invention, when producing -α-tocopherol, 2.3.5-1-tmethyl-1,4-benzoquinone is used as a starting material, and this is reduced using a reducing agent to produce 2.
．． 3.5-)limethylhydroquinone, and then the obtained 2,3. ．． 5-) A method for producing α-tocopherol, characterized in that phytols are added to the reaction solution without removing the remethylhydroquinone form from the reaction solution, and a condensation reaction is carried out using metal zinc and zinc chloride as catalysts. be.
即ち、本発明の方法は、２．３．５− ）リフチル−１
，４−ベンゾキノンを出発物質として、還元、縮合反応
の連続操作を経て、ａ−α−トコフェロールを製造する
方法に関するものである。That is, the method of the present invention comprises: 2.3.5-) rifutyl-1
The present invention relates to a method for producing a-α-tocopherol using ,4-benzoquinone as a starting material through continuous reduction and condensation reactions.
本発明方法の特徴は、出発物質として２，３．５−トリ
メチル−１，４−ベンゾキノンを用い、中間体としての
２．３．５− ）リメチルハイドロキノンを粉体として
取り出すことなく、反応機構的に考えると次の工程とす
るフィトール類との縮合反応を連続的に行うことである
。The feature of the method of the present invention is that 2,3.5-trimethyl-1,4-benzoquinone is used as a starting material, and the reaction mechanism is Considering this, the next step is to carry out the condensation reaction with phytols continuously.
この際、還元剤としては、具体的には例えば金属亜鉛及
び硫酸；金属亜鉛、塩酸及び酢酸；金属亜鉛及び塩酸ガ
ス；ハイドロサルファイドなどが好ましいが、最も好ま
しい例を挙げれば金属亜鉛・３５％硫酸水溶液法を挙げ
ることができる。At this time, specific examples of the reducing agent include metal zinc and sulfuric acid; metal zinc, hydrochloric acid, and acetic acid; metal zinc and hydrochloric acid gas; and hydrosulfide. An example is an aqueous solution method.
金属亜鉛の形態は、粉末、顆粒、薄片などがあるが、粉
末が最も好ましい結果を与える。Metallic zinc can be in the form of powder, granules, flakes, etc., but powder gives the most favorable results.
還元反応を行う際は、通常溶媒中に還元剤を加え還元反
応を行うが、溶媒としては酢酸エステル類、例えば酢酸
メチル、酢酸エチル、酢酸プロピル、酢酸イソプロピル
等が挙げられるが、これらのうち酢酸エチルが最も好ま
しい。When carrying out a reduction reaction, a reducing agent is usually added to a solvent to carry out the reduction reaction. Examples of solvents include acetate esters, such as methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, etc. Among these, acetic acid Ethyl is most preferred.
また還元反応終了後、通常金属亜鉛を常法により除去し
、次いで水洗後、酢酸エチルをスラリー状になるまで留
去する方法が最も好ましい結果を与える。Further, after the completion of the reduction reaction, the most preferable result is usually obtained by removing metallic zinc by a conventional method, then washing with water, and then distilling off ethyl acetate until it becomes a slurry.
フィトール類としては、フィトール、イソフイトールな
どを挙げることができる。Examples of phytols include phytol and isophytol.
また、本発明においては、触媒として金属亜鉛及び塩化
亜鉛と共に、無水酢酸を加えて反応させることにより、
ａ−α−トコフェロールアセテートを得ることができる
。この場合、ミーα−トコフェロールを反応中で取り出
さなくてもよい。In addition, in the present invention, by adding acetic anhydride and reacting with metal zinc and zinc chloride as a catalyst,
a-α-tocopherol acetate can be obtained. In this case, it is not necessary to remove me-α-tocopherol during the reaction.
本発明方法によれば、出発物質として２．３．５−トリ
メチルハイドロキノン体を使用しないため、前述した欠
点がなく、更に２．３．５−トリメチル−１，４−ベン
ゾキノンを用いて接触水素添加反応を行う従来の方法と
比較して、金属亜鉛、硫酸などを使用できるため、工業
化が容易である。更に原料も安価であるため、工業的生
産上、大きなメリットがある。According to the method of the present invention, since 2.3.5-trimethylhydroquinone is not used as a starting material, the above-mentioned drawbacks are not present, and furthermore, 2.3.5-trimethyl-1,4-benzoquinone is used for catalytic hydrogenation. Compared to conventional methods of carrying out the reaction, it is easier to industrialize because metallic zinc, sulfuric acid, etc. can be used. Furthermore, since the raw materials are inexpensive, there is a great advantage in industrial production.
結局、本発明方法によれば、高純度のｄｌ−トコフェロ
ールを高収率に製造することが可能であり、工業的価値
は極めて高いものである。After all, according to the method of the present invention, it is possible to produce highly purified dl-tocopherol in high yield, and the industrial value is extremely high.
以下に、本発明の具体的な実施例を挙げるが、本発明が
これらのみに限定されることがないことはいうまでもな
い。Specific examples of the present invention are listed below, but it goes without saying that the present invention is not limited only to these examples.
尚、実施例において、ＴＭＢＱとは、２，３．５−トリ
メチル−１，４−ベンゾキノンを意味する。In addition, in the examples, TMBQ means 2,3.5-trimethyl-1,4-benzoquinone.
実施例Ｉ
ＴＭＢＱ ６０．０ ｇに酢酸エチル２５０ ｍｌ、３
５％硫酸１５５．０ ｇを加え、攪拌下、金属亜鉛３０
．０ｇを添加した。添加終了後水層を分離し、有機層を
水洗、濃縮してスラリー状にした。Example I 250 ml of ethyl acetate to 60.0 g of TMBQ, 3
Add 155.0 g of 5% sulfuric acid and add 30 g of metallic zinc while stirring.
．． 0g was added. After the addition was completed, the aqueous layer was separated, and the organic layer was washed with water and concentrated to form a slurry.
このスラリー液に塩化亜鉛５７．５ｇ、金属亜鉛０．５
ｇ、酢酸５．０ｇ、濃塩酸６．０ｇを加え、４０℃でイ
ソフィトール１００．０ ｇを３時間で滴下した。滴下
終了後、更に１．５時間反応を続けた。This slurry liquid contains 57.5 g of zinc chloride and 0.5 g of metallic zinc.
g, acetic acid 5.0 g, and concentrated hydrochloric acid 6.0 g were added, and 100.0 g of isophytol was added dropwise at 40° C. over 3 hours. After the dropwise addition was completed, the reaction was continued for an additional 1.5 hours.
縮合反応終了後、水洗、アルカリ水洗し、常法に従いア
セチル化し、淡黄色油状の粗ａ−α−トコフェロールア
セテート１５３．２ ｇを得た。After the condensation reaction was completed, the mixture was washed with water and alkaline water, and acetylated according to a conventional method to obtain 153.2 g of pale yellow oily crude a-α-tocopherol acetate.
この粗８−α−トコフェロールアセテートを分子蒸留に
より精製し、純度９９．５％のｄｌ−トコフェロールア
セテートを得た。This crude 8-α-tocopherol acetate was purified by molecular distillation to obtain dl-tocopherol acetate with a purity of 99.5%.
実施例２
ＴＭＢロ６０．０ ｇに酢酸エチル２５０ ｍｌ、酢酸
５０．０ｇ、ｔ！塩酸５．０ｇを加え、攪拌上金属亜鉛
３０．０ｇを添加した。Example 2 250 ml of ethyl acetate, 50.0 g of acetic acid, t! 5.0 g of hydrochloric acid was added, and after stirring, 30.0 g of metallic zinc was added.
以下、実施例１と同様にして粗〃−α−トコフェロール
アセテート１５２．８ ｇを得た。Thereafter, 152.8 g of crude -α-tocopherol acetate was obtained in the same manner as in Example 1.
この粗〃−α−トコフェロールアセテートを分子蒸留に
より精製し、純度９９．０％の〃−α−トコフェロール
アセテートを得た。This crude α-tocopherol acetate was purified by molecular distillation to obtain 99.0% pure α-tocopherol acetate.
実施例３
ＴＭＢ［１６０，０ｇに酢酸エチル５００ ｖｎｌ、２
０％ハイドロサルファイド水溶液５２０．０ｇを加え、
攪拌上室温で２時間反応した。Example 3 TMB [500 vnl of ethyl acetate in 160.0 g, 2
Add 520.0g of 0% hydrosulfide aqueous solution,
The mixture was stirred and reacted at room temperature for 2 hours.
還元反応終了後、水層を分離し、有機層を濃縮してスラ
リー状にした。その後、実施例１の方法と同様に、縮合
反応、アセチル化反応を行い、粗〃−α−トコフェロー
ルアセテ−） １４５．０ｇを得た。After the reduction reaction was completed, the aqueous layer was separated and the organic layer was concentrated to form a slurry. Thereafter, a condensation reaction and an acetylation reaction were performed in the same manner as in Example 1 to obtain 145.0 g of crude (α-tocopherol acetate).
この粗ａ−α−トコフェロールアセテートを分子蒸留に
より精製し、純度９９．０％のみ−α−トコフェロール
アセテートを得た。This crude a-α-tocopherol acetate was purified by molecular distillation to obtain -α-tocopherol acetate with a purity of only 99.0%.
実施例４
ＴＭＢＱ ６０．０ ｇに酢酸エチル２４０ ｍｌ、金
属亜鉛３６．０ｇを加え、攪拌正塩酸ガスを通じた。Example 4 240 ml of ethyl acetate and 36.0 g of metal zinc were added to 60.0 g of TMBQ, and agitated normal hydrochloric acid gas was passed through the mixture.
更にこれに酢酸４．８−を加え、塩酸ガスを通じ４０℃
でイソフィトール１００．０ ｇを３時間で滴下した。Furthermore, acetic acid 4.8- was added to this, and the mixture was heated at 40°C through hydrochloric acid gas.
100.0 g of isophytol was added dropwise over 3 hours.
滴下終了後更に１時間反応を続けた。After the dropwise addition was completed, the reaction was continued for an additional hour.
縮合反応終了後、実施例１の方法と同様に処理して、粗
〃−α−トコフェロールアセテート１４５．１ ｇを得
た。After the condensation reaction was completed, it was treated in the same manner as in Example 1 to obtain 145.1 g of crude -α-tocopherol acetate.
この粗ａ−α−トコフェロールアセテートを分子蒸留に
より精製し、純度９９．０％のａ−α−トコフェロール
アセテートを得た。This crude a-α-tocopherol acetate was purified by molecular distillation to obtain a-α-tocopherol acetate with a purity of 99.0%.
実施例５
ＴＭＢＱ ６０．０ ｇに酢酸エチル２４０ｍ／、金属
亜鉛３６．０ ｇを加え、攪拌正塩酸ガスを通じた。更
に酢酸４．８−１濃塩酸４．８ｍ／、塩化亜鉛５４．５
ｇを加え４０℃でイソフィトール１００．０ ｇを３
時間で滴下した。Example 5 To 60.0 g of TMBQ were added 240 m/ml of ethyl acetate and 36.0 g of metallic zinc, and agitated normal hydrochloric acid gas was passed through the mixture. Furthermore, acetic acid 4.8-1 concentrated hydrochloric acid 4.8 m/, zinc chloride 54.5
Add 100.0 g of isophytol at 40℃.
It dripped in time.
以下、実施例１と同様にして、粗〃−α−トコフェロー
ルアセテート１４８．３ ｇヲ得り。Thereafter, in the same manner as in Example 1, 148.3 g of crude -α-tocopherol acetate was obtained.
この粗ａ−α−トコフェロールアセテートを分子蒸留に
より精製して純度９９．２％のｄｌ−トコフェロールア
セテートを得た。This crude a-α-tocopherol acetate was purified by molecular distillation to obtain dl-tocopherol acetate with a purity of 99.2%.
実施例６
ＴＭＢＱ ６０．０ ｇに酢酸イソプロピル２５０−１
３５％硫酸１５５．０ ｇを加え、攪拌下、金属亜鉛３
０．０ｇを添加した。Example 6 Isopropyl acetate 250-1 to 60.0 g TMBQ
Add 155.0 g of 35% sulfuric acid and add 3.0 g of metallic zinc while stirring.
0.0g was added.
以下、実施例１と同様にして、粗〃−α−トコフェロー
ルアセテート１５２．０ ｇを得た。Thereafter, in the same manner as in Example 1, 152.0 g of crude -α-tocopherol acetate was obtained.
この粗ａ−α−トコフェロールアセテートを分子蒸留に
より精製し純度９９．０％の８−α−トコフェロールア
セテートを得た。This crude a-α-tocopherol acetate was purified by molecular distillation to obtain 8-α-tocopherol acetate with a purity of 99.0%.
Claims (1)
３，５−トリメチル−１，４−ベンゾキノンを出発物質
とし、これを還元剤を用いて還元して、２，３，５−ト
リメチルハイドロキノンとし、次いで得られた２，３，
５−トリメチルハイドロキノン体を反応液から取りだす
ことなく、該液にフィトール類を加え、触媒として金属
亜鉛及び塩化亜鉛を用いて縮合反応せしめることを特徴
とするｄｌ−α−トコフェロールの製造方法。 ２ 金属亜鉛及び硫酸からなる還元剤を用いて還元する
特許請求の範囲第１項記載のｄｌ−α−トコフェロール
の製造方法。 ３ 金属亜鉛、塩酸及び酢酸からなる還元剤を用いて還
元する特許請求の範囲第１項記載のｄｌ−α−トコフェ
ロールの製造方法。 ４ 金属亜鉛及び塩酸ガスからなる還元剤を用いて還元
する特許請求の範囲第１項記載のｄｌ−α−トコフェロ
ールの製造方法。 ５ ハイドロサルファイドからなる還元剤を用いて還元
する特許請求の範囲第１項記載のｄｌ−α−トコフェロ
ールの製造方法。[Claims] 1. When producing dl-α-tocopherol, 2.
Using 3,5-trimethyl-1,4-benzoquinone as a starting material, this is reduced using a reducing agent to give 2,3,5-trimethylhydroquinone, and then the obtained 2,3,
A method for producing dl-α-tocopherol, which comprises adding phytols to the reaction solution without removing the 5-trimethylhydroquinone form from the reaction solution, and causing a condensation reaction using metal zinc and zinc chloride as catalysts. 2. The method for producing dl-α-tocopherol according to claim 1, which comprises reducing using a reducing agent consisting of metal zinc and sulfuric acid. 3. The method for producing dl-α-tocopherol according to claim 1, which comprises reducing using a reducing agent consisting of metallic zinc, hydrochloric acid, and acetic acid. 4. The method for producing dl-α-tocopherol according to claim 1, which comprises reducing using a reducing agent consisting of metallic zinc and hydrochloric acid gas. 5. The method for producing dl-α-tocopherol according to claim 1, which comprises reducing using a reducing agent consisting of hydrosulfide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61070553A JPH0772184B2 (en) | 1986-03-28 | 1986-03-28 | Method for producing d-l-α-tocopherol |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61070553A JPH0772184B2 (en) | 1986-03-28 | 1986-03-28 | Method for producing d-l-α-tocopherol |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS62226976A true JPS62226976A (en) | 1987-10-05 |
| JPH0772184B2 JPH0772184B2 (en) | 1995-08-02 |
Family
ID=13434829
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61070553A Expired - Lifetime JPH0772184B2 (en) | 1986-03-28 | 1986-03-28 | Method for producing d-l-α-tocopherol |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0772184B2 (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000017185A1 (en) * | 1998-09-18 | 2000-03-30 | Aventis Animal Nutrition S.A. | Method for preparing vitamin e |
| CN1060166C (en) * | 1994-03-09 | 2001-01-03 | 武田药品工业株式会社 | Process for producing DL-tocopherols and intermediates therefor |
| EP2269998A2 (en) | 2004-08-19 | 2011-01-05 | DSM IP Assets B.V. | Process for the rectification of mixtures of high-boiling air- and/or temperature-sensitive useful products |
| JP2013063912A (en) * | 2011-08-31 | 2013-04-11 | Eisai R & D Management Co Ltd | PRODUCTION METHOD OF α-TOCOPHEROL AND ACETIC ACID α-TOCOPHEROL |
| CN103450473A (en) * | 2013-09-09 | 2013-12-18 | 湖北吉和昌化工科技有限公司 | Preparation method of N, N'-bis(dimethylamino alkyl) ureido-alpha, omega-dihalo alkyl copolymer |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS50157367A (en) * | 1974-06-10 | 1975-12-19 | ||
| JPS56169686A (en) * | 1980-06-02 | 1981-12-26 | Shiseido Co Ltd | Preparation of vitamine e homolog and its analoqous compound |
-
1986
- 1986-03-28 JP JP61070553A patent/JPH0772184B2/en not_active Expired - Lifetime
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS50157367A (en) * | 1974-06-10 | 1975-12-19 | ||
| JPS56169686A (en) * | 1980-06-02 | 1981-12-26 | Shiseido Co Ltd | Preparation of vitamine e homolog and its analoqous compound |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1060166C (en) * | 1994-03-09 | 2001-01-03 | 武田药品工业株式会社 | Process for producing DL-tocopherols and intermediates therefor |
| WO2000017185A1 (en) * | 1998-09-18 | 2000-03-30 | Aventis Animal Nutrition S.A. | Method for preparing vitamin e |
| FR2784104A1 (en) * | 1998-09-18 | 2000-04-07 | Rhone Poulenc Nutrition Animal | PROCESS FOR PREPARING VITAMIN E |
| US6790967B2 (en) | 1998-09-18 | 2004-09-14 | Adisseo France S.A.S. | Process for the preparation of vitamin E |
| EP2269998A2 (en) | 2004-08-19 | 2011-01-05 | DSM IP Assets B.V. | Process for the rectification of mixtures of high-boiling air- and/or temperature-sensitive useful products |
| JP2013063912A (en) * | 2011-08-31 | 2013-04-11 | Eisai R & D Management Co Ltd | PRODUCTION METHOD OF α-TOCOPHEROL AND ACETIC ACID α-TOCOPHEROL |
| CN103450473A (en) * | 2013-09-09 | 2013-12-18 | 湖北吉和昌化工科技有限公司 | Preparation method of N, N'-bis(dimethylamino alkyl) ureido-alpha, omega-dihalo alkyl copolymer |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0772184B2 (en) | 1995-08-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN114436924B (en) | Synthesis method of hydroxy pinacolone retinoic acid ester | |
| JPS62226976A (en) | Production of dl-alpha-tocopherol | |
| US5155234A (en) | Nitration of phthalic acid and phthalic anhydride using nitric acid | |
| CN115286514B (en) | Preparation method of 4' -chloro-2-aminobiphenyl sulfate | |
| CN115010592B (en) | Preparation method of 4-bromophthalic acid | |
| CN111269149B (en) | Production process of 5- (3,3-dimethylguanidino) -2-oxopentanoic acid | |
| US7247758B2 (en) | Method for producing 2,3,6,7,10,11-hexahydroxytriphenylene | |
| JPH0559116B2 (en) | ||
| US4252726A (en) | Preparation of dl-α-tocopherol | |
| JPH03215455A (en) | Production of aromatic bisanilines | |
| KR20010031559A (en) | Preparation of quinonediimines from phenylenediamines using hydrogen peroxide and a catalyst | |
| CN107935876B (en) | Preparation method of 2- (3-amino-4-chlorobenzoyl) benzoic acid | |
| JPH05202020A (en) | Preparation of highly pure tocopheryl retinoate | |
| JP3168079B2 (en) | Method for producing 2-alkylformylimidazole | |
| EP1535918B1 (en) | Process for producing aminobenzopyran compound | |
| KR20050043131A (en) | Preparation method of 4-biphenylacetic acid | |
| CN116903486A (en) | Preparation method of 4,4' -diaminobenzophenone | |
| JPS62298546A (en) | Production of anisaldehyde | |
| JPS6064977A (en) | Praparation of alpha-tocopherol | |
| JPS6072881A (en) | Production of alpha-tocopherol | |
| JPH07165687A (en) | Production of 5-fluoroanthranilic acid | |
| JPS6330906B2 (en) | ||
| CN115724728A (en) | Synthesis process of 1, 7-dichloro-4-heptanone | |
| WO1985002615A1 (en) | Nitration of phthalic acid and phthalic anhydride using nitric acid | |
| JPH07233130A (en) | Production of aminobenzoic alkyl ester |