JPS6035347B2 - Synthesis method of α-tocopherol - Google Patents

Synthesis method of α-tocopherol

Info

Publication number
JPS6035347B2
JPS6035347B2 JP8810876A JP8810876A JPS6035347B2 JP S6035347 B2 JPS6035347 B2 JP S6035347B2 JP 8810876 A JP8810876 A JP 8810876A JP 8810876 A JP8810876 A JP 8810876A JP S6035347 B2 JPS6035347 B2 JP S6035347B2
Authority
JP
Japan
Prior art keywords
tocopherol
acid
purity
producing
parts
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.)
Expired
Application number
JP8810876A
Other languages
Japanese (ja)
Other versions
JPS5315381A (en
Inventor
千秋 関
清 相沢
義博 古賀
優介 小西
吉三郎 浜村
静正 貴島
昭麿 野中
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Eisai Co Ltd
Original Assignee
Eisai Co Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Eisai Co Ltd filed Critical Eisai Co Ltd
Priority to JP8810876A priority Critical patent/JPS6035347B2/en
Publication of JPS5315381A publication Critical patent/JPS5315381A/en
Publication of JPS6035347B2 publication Critical patent/JPS6035347B2/en
Expired legal-status Critical Current

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Description

【発明の詳細な説明】 本発明はQ−トコフェロールの新規な合成法に関するも
のである。
DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for synthesizing Q-tocopherol.

さらに詳しくは、酸縮合剤と不活性溶媒の存在下に、2
・3・5ートリメチルハィドロキノンとフィトール類を
縮合することよりなるQ−トコフェロールの合成法にお
いて、酸縮合剤として塩化亜鉛と燐酸類、不活性溶媒と
して低級脂肪族ハロゲン化水素系溶媒を使用することよ
りなるQートコフェロールの合成法に関するものである
。本発明の方法において使用される低級脂肪族ハロゲン
化水素系溶剤としては、例えばジクロルメタン、クロロ
ホルム、四塩化炭素、エチレンジクロラィド等を挙げる
ことができる。
More specifically, in the presence of an acid condensing agent and an inert solvent, 2
・In the synthesis method of Q-tocopherol, which involves condensing 3,5-trimethylhydroquinone and phytols, zinc chloride and phosphoric acids are used as acid condensing agents, and lower aliphatic hydrogen halide solvents are used as inert solvents. The present invention relates to a method for synthesizing Q-tocopherol, which comprises the following steps. Examples of the lower aliphatic hydrogen halide solvent used in the method of the present invention include dichloromethane, chloroform, carbon tetrachloride, and ethylene dichloride.

特にジクロルメタンは目的物の純度および収率に一層好
ましい結果を与えた。本発明の方法における酸縮合剤と
しては、塩化亜鉛と燐酸類を用いるが、燐酸類としては
燐酸、ポリIJン酸等を挙げることができ、塩化亜鉛の
燐酸類に対する割合は、塩化亜鉛1モルに対し燐酸類0
.01〜0.5モルが望ましい。
In particular, dichloromethane gave more favorable results in terms of purity and yield of the target product. Zinc chloride and phosphoric acids are used as the acid condensing agent in the method of the present invention, and examples of the phosphoric acids include phosphoric acid, poly-IJ phosphoric acid, etc., and the ratio of zinc chloride to phosphoric acids is 1 mole of zinc chloride. 0 phosphoric acids
.. 01 to 0.5 mol is desirable.

本発明において使用されるフィトール類としては、フイ
トール、イソフイトールおよびそれらの類縁化合物を挙
げることができる。
The phytols used in the present invention include phytol, isophytol, and their analogs.

本発明においては、反応は室温で進行し、加熱還流等の
操作は不要である。
In the present invention, the reaction proceeds at room temperature, and operations such as heating to reflux are not necessary.

また反応に際して、反応系に酢酸、プロピオン酸等の有
機酸および亜鉛末筆を添加して、反応の円滑化および目
的物の収率、品質の向上を図ることができる。従来、Q
ートコフェロールの製造法として、2・3・5−トリメ
チルハイドロキノソとフイトールおよび/またはィソフ
ィトールを縮合せしめるのに際し、塩化亜鉛を縮合剤と
して使用し、リグロイン、テトラリン、ベンゼン、トル
エン、キシレンなどの脂肪族炭化水素系溶媒中で加熱還
流する方法が知られている。
Further, during the reaction, an organic acid such as acetic acid or propionic acid and zinc dust can be added to the reaction system to facilitate the reaction and improve the yield and quality of the target product. Conventionally, Q
As a method for producing tocopherol, when condensing 2,3,5-trimethylhydroquinoso with phytol and/or isophytol, zinc chloride is used as a condensing agent, and aliphatic compounds such as ligroin, tetralin, benzene, toluene, and xylene are used. A method of heating under reflux in a hydrocarbon solvent is known.

しかし、これら従釆方法では高温における加熱還流と云
う苛酷な反応条件が必須であるために、例えばフィタジ
ェンおよびその重合体、溶媒とフィトール類の反応物等
の各種の好ましくない副生物が生成し、これらは蒸留に
よる精製操作では除去困難であり、そのために高収率で
高純度のQ−トコフェロールを得ることはできない。従
って、これらの欠点を除去するために、単に反応を比較
的低温で行うことが考えられるが、低温では反応の進行
性が低く、Q−トコフェロールの収率は著しく低下する
。本発明者等は従来のQ−トコフェロール製造法の上記
した欠点を除去して、高純度のQ−トコフェロールを高
収率で得るための研究を行い、分離精製の困難な好まし
くない不純物が副生しない縮合方法の探索のため、種々
の縮合方法を検討した結果、高純度のQ−トコフェロー
ルを高収率で提供する本発明の方法を見出した。
However, since these conventional methods require harsh reaction conditions such as heating under reflux at high temperatures, various undesirable by-products are produced, such as phytagene and its polymers, and reaction products of solvents and phytols. These substances are difficult to remove by purification by distillation, and therefore high yield and high purity Q-tocopherol cannot be obtained. Therefore, in order to eliminate these drawbacks, it is conceivable to simply carry out the reaction at a relatively low temperature, but at low temperatures the progress of the reaction is low and the yield of Q-tocopherol is significantly reduced. The present inventors conducted research to eliminate the above-mentioned drawbacks of the conventional Q-tocopherol production method and obtain high-purity Q-tocopherol in high yield. As a result of examining various condensation methods in order to search for a condensation method that does not cause the above-described conditions, the method of the present invention that provides highly pure Q-tocopherol in high yield was discovered.

本発明の方法の利点は、縮合反応を行うに際して、高温
における加熱還流を行う必要もなく、20〜40ooの
緩和な温度条件で反応がほぼ定量的に進行する。
The advantage of the method of the present invention is that when carrying out the condensation reaction, there is no need to perform heating under reflux at a high temperature, and the reaction proceeds almost quantitatively under mild temperature conditions of 20 to 40 degrees Celsius.

その結果、従来法のような苛酷な反応条件による副生成
物の生成も僅少であり、しかも収率95%以上と云う高
収率で粗Q−トコフェロールを得ることができた。
As a result, the production of by-products due to the harsh reaction conditions of the conventional method was minimal, and crude Q-tocopherol could be obtained at a high yield of 95% or more.

この粗はートコフェロールを常法に従って分子蒸留した
場合、純度98%以上〔ナショ ナル ホ ーミユ
ラリー(NationalFormulary)第14
登第758〜762頁記載のガスクロマト法によるビタ
ミンE定量法に従って測定した。〕の精製Qートコフェ
ロールを96%以上の収率で得られると云う好結果が得
られた。また従来法と比較して副生成物の爽難が少ない
ことは、ガスクロマトグラフ上あるいは薄層クロマトグ
ラフ上でも確認された。以上より本発明は、従来法に比
してより高純度のQ−トコフェロールを、より高収率で
提供する事をその目的とするものである。
When this crude tocopherol is molecularly distilled using a conventional method, it has a purity of 98% or more [National Homilies].
Rally (National Formulary) No. 14
It was measured according to the vitamin E quantitative method using gas chromatography described on pages 758 to 762 of the publication. Good results were obtained in that purified Q tocopherol could be obtained in a yield of 96% or more. It was also confirmed on gas chromatography or thin layer chromatography that the by-products were less refreshing compared to conventional methods. In view of the above, an object of the present invention is to provide Q-tocopherol with higher purity and higher yield than conventional methods.

次に実施例により本発明を説明する。Next, the present invention will be explained with reference to Examples.

なお、目的物Qートコフェロールの純度は前記したナシ
ョナル ホーミュラリー第14仮託戦のガスクロマト法
に従って測定した。実施例 1 2・3・5−トリメチルハイドロキノン125夕、塩化
亜鉛112夕、亜鉛末5夕、ジクロルメタン350の【
および燐酸30夕を混合礎投下、25〜30ooでィソ
フィトール245夕(純度98.1%)を3時間を要し
て滴下、さらに同温度で1時間凝洋を行った。
Note that the purity of the target substance Q tocopherol was measured according to the gas chromatography method of the National Homulary No. 14 Test, described above. Example 1 125% of 2,3,5-trimethylhydroquinone, 112% of zinc chloride, 5% of zinc powder, 350% of dichloromethane [
A mixed base of 30 liters of phosphoric acid and 30 liters of phosphoric acid was added, and 245 liters of isophytol (purity 98.1%) was added dropwise over 3 hours at 25 to 30 ounces, followed by condensation for 1 hour at the same temperature.

反応終了後水50の‘を加え、塩化亜鉛を除き、常温で
ジクロルメタンを留去し、得られた油状物残溝(粗Qー
トコフェロール)をトルェン300の‘、メチルエチル
ケトン10帆【に溶解し、水洗、アルカリ洗、水洗後ア
セチル化を行い、水洗後、濃縮し、淡黄色油状のQート
コフェロールアセテート382.1夕を得た。純度96
.0%、収率95.7本品を分子蒸留に附し、無色油状
物質(精製Q−トコフェリールアセテート)357.9
夕(純度98.7%)を得た。実施例 2 2・3・5ートリメチルハイドロキノン125夕、塩化
亜鉛112夕、亜鉛末5夕、ジクロルメタン450叫、
ポリ燐酸(P.P.A.)10夕、酢酸20夕およびィ
ソフィトール245夕(純度98.1%)を実施例1に
従って反応処理し、澄色油状物の粗Qートコフェロール
348.8夕を得た。
After the reaction, 50 parts of water was added, zinc chloride was removed, dichloromethane was distilled off at room temperature, and the resulting oil residue (crude Q tocopherol) was dissolved in 300 parts of toluene and 10 parts of methyl ethyl ketone. Washing with water, washing with alkali, and acetylation after washing with water were carried out. After washing with water, the mixture was concentrated to obtain 382.1 kg of Q tocopherol acetate as a pale yellow oil. Purity 96
.. 0%, yield 95.7 This product was subjected to molecular distillation to produce a colorless oily substance (purified Q-tocopheryl acetate) 357.9
An aqueous solution (purity 98.7%) was obtained. Example 2 2,3,5-trimethylhydroquinone 125 times, zinc chloride 112 times, zinc powder 5 times, dichloromethane 450 times,
10 parts of polyphosphoric acid (P.P.A.), 20 parts of acetic acid and 245 parts of isophytol (purity 98.1%) were reacted according to Example 1 to give 348.8 parts of crude Q tocopherol as a clear oil. Obtained.

純度95.3%、収率95.2%本品を分子蒸留に附し
、淡黄色油状物質の精製Q−トコフェ。ール331.4
夕(純度98.1%)を得た。実施例 3 2・3・5−トリメチルハイド。
Purity 95.3%, yield 95.2% This product was subjected to molecular distillation to produce purified Q-tocofe as a pale yellow oily substance. Rule 331.4
An aqueous solution (purity 98.1%) was obtained. Example 3 2,3,5-trimethylhyde.

キノン125夕、塩化亜鉛112夕、亜鉛末5夕、ジク
ロルメタン300地、酢酸30夕、燐酸15夕およびイ
ソフイトール245夕(純度98.1%)を実施例1に
従って反応処理し、淡黄色油状物の粗Q−トコフェリー
ルアセテート382.79を得た。純度96.7%、収
率96.6%次に参考例を託し、本発明と比較する。
125 parts of quinone, 112 parts of zinc chloride, 5 parts of zinc powder, 300 parts of dichloromethane, 30 parts of acetic acid, 15 parts of phosphoric acid and 245 parts of isophytol (purity 98.1%) were reacted according to Example 1 to give a pale yellow oil. 382.79 of crude Q-tocopheryl acetate was obtained. Purity: 96.7%, Yield: 96.6% Next, a reference example is given and compared with the present invention.

参考例 1 2・3・5−トリメチルハイドロキノン125夕、塩化
亜鉛112夕、亜鉛末59、ジクロルメタン300瓜‘
、酢酸30の,【を混合樹梓下、25〜300Cでィソ
フィトール245夕(純度98.1%)を3時間を要し
て滴下、さらに同温度で1時間損拝を行った。
Reference example 1 125 units of 2,3,5-trimethylhydroquinone, 112 units of zinc chloride, 59 units of zinc powder, 300 units of dichloromethane
, 30% of acetic acid was mixed with a mixture of azaleas, and 245% of isophytol (purity 98.1%) was added dropwise at 25 to 300C over a period of 3 hours, and the mixture was further heated at the same temperature for 1 hour.

Claims (1)

【特許請求の範囲】 1 酸縮合剤と不活性溶媒の存在下に、2・3・5−ト
リメチルハイドロキノンとフイトール類を縮合せしめて
、α−トコフエロールを製造する方法において、酸縮合
剤として塩化亜鉛と燐酸類、不活性溶媒として低級脂肪
族ハロゲン化水素系溶媒を使用することを特徴とするα
−トコフエロールの製造方法。 2 低級脂肪族ハロゲン化水素系溶媒が、ジクロルメタ
ン、クロロホルム、四塩化炭素、エチレンジクロライド
から選択された溶媒である特許請求の範囲第1項記載の
α−トコフエロールの製造方法。 3 燐酸類が、燐酸またはポリリン酸である特許請求の
範囲第1項記載のα−トコフエロールの製造方法。 4 燐酸類が燐酸であり、低級脂肪族ハロゲン化水素系
溶媒がジクロルメタンである特許請求の範囲第1項記載
のα−トコフエロールの製造法。
[Claims] 1. A method for producing α-tocopherol by condensing 2,3,5-trimethylhydroquinone and phytols in the presence of an acid condensing agent and an inert solvent, in which zinc chloride is used as the acid condensing agent. and phosphoric acids, and α characterized by using a lower aliphatic hydrogen halide solvent as an inert solvent.
- A method for producing tocopherols. 2. The method for producing α-tocopherol according to claim 1, wherein the lower aliphatic hydrogen halide solvent is a solvent selected from dichloromethane, chloroform, carbon tetrachloride, and ethylene dichloride. 3. The method for producing α-tocopherol according to claim 1, wherein the phosphoric acid is phosphoric acid or polyphosphoric acid. 4. The method for producing α-tocopherol according to claim 1, wherein the phosphoric acid is phosphoric acid, and the lower aliphatic hydrogen halide solvent is dichloromethane.
JP8810876A 1976-07-26 1976-07-26 Synthesis method of α-tocopherol Expired JPS6035347B2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP8810876A JPS6035347B2 (en) 1976-07-26 1976-07-26 Synthesis method of α-tocopherol

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP8810876A JPS6035347B2 (en) 1976-07-26 1976-07-26 Synthesis method of α-tocopherol

Publications (2)

Publication Number Publication Date
JPS5315381A JPS5315381A (en) 1978-02-13
JPS6035347B2 true JPS6035347B2 (en) 1985-08-14

Family

ID=13933670

Family Applications (1)

Application Number Title Priority Date Filing Date
JP8810876A Expired JPS6035347B2 (en) 1976-07-26 1976-07-26 Synthesis method of α-tocopherol

Country Status (1)

Country Link
JP (1) JPS6035347B2 (en)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997028151A1 (en) * 1996-01-29 1997-08-07 Basf Aktiengesellschaft METHOD OF PRODUCING DL-α-TOCOPHEROL OR DL-α-TOCOPHERYL ACETATE
AUPP829399A0 (en) * 1999-01-25 1999-02-18 Swig Pty Ltd Recovery for chroman derivatives
EP2531047A4 (en) 2010-02-05 2014-03-19 Phosphagenics Ltd Carrier comprising non-neutralised tocopheryl phosphate
US9561243B2 (en) 2011-03-15 2017-02-07 Phosphagenics Limited Composition comprising non-neutralised tocol phosphate and a vitamin A compound
JP2013063912A (en) * 2011-08-31 2013-04-11 Eisai R & D Management Co Ltd PRODUCTION METHOD OF α-TOCOPHEROL AND ACETIC ACID α-TOCOPHEROL
CN108601732A (en) 2015-12-09 2018-09-28 磷肌酸有限公司 pharmaceutical preparation
WO2018112512A1 (en) 2016-12-21 2018-06-28 Phosphagenics Limited Process

Also Published As

Publication number Publication date
JPS5315381A (en) 1978-02-13

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