JPS5857373A - Preparation of l-ascorbic acid derivative - Google Patents
Preparation of l-ascorbic acid derivativeInfo
- Publication number
- JPS5857373A JPS5857373A JP56156860A JP15686081A JPS5857373A JP S5857373 A JPS5857373 A JP S5857373A JP 56156860 A JP56156860 A JP 56156860A JP 15686081 A JP15686081 A JP 15686081A JP S5857373 A JPS5857373 A JP S5857373A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- compound
- ascorbic acid
- aralkyl
- isopropylidene
- 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
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
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Furan Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
本発明はＬ−アスコルビン酸洒導体の新規な製法に関す
る。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for producing L-ascorbic acid-based conductors.
Ｌ−アスコルビン酸、すなわち、ビタミンＣは、近年、
ますますその重要性が明らかにされつつあるか、ビタミ
ンＣは非常に酸化分解を受けやすく、特に中性または塩
基性水溶液中では不安定で、医薬品、化粧品、口腔剤等
への配合かなかなか難しい。L-ascorbic acid, that is, vitamin C, has recently been
Perhaps because its importance is becoming increasingly clear, vitamin C is extremely susceptible to oxidative decomposition and is particularly unstable in neutral or basic aqueous solutions, making it difficult to incorporate it into pharmaceuticals, cosmetics, oral preparations, etc. .
近年、１・−アスコルビン酸の３−０−メチルおよび３
−０−ベンジル誘導体か報告されており、これらは水溶
液中できわめて安定であり、医薬品、化粧品、口腔剤へ
配合するのに適している。従来これらの誘導体は無水メ
タン−ル中、Ｌ−アスコルビン酸をジアゾメタンで処理
して３−０−メチル化シたり、含水アセトン中でＩ−−
アスコルビン酸を塩化ベンジルと反応させて３−０−ベ
ンジル化して製造されるが、いずれも副生物か多量に生
成し、目的物の収率か低い。In recent years, 3-0-methyl and 3 of 1-ascorbic acid
-0-benzyl derivatives have been reported, and these are extremely stable in aqueous solutions and are suitable for inclusion in pharmaceuticals, cosmetics, and oral preparations. Conventionally, these derivatives have been prepared by treating L-ascorbic acid with diazomethane in anhydrous methanol to obtain 3-0-methylation, or by converting I-- into 3-0-methylation in aqueous acetone.
It is produced by reacting ascorbic acid with benzyl chloride to form 3-0-benzylation, but both produce large amounts of by-products and the yield of the target product is low.
！
本発明は該３−０−メチルおよび３−０−ベンジル誘導
体を含め、式：
％式％
〔式中、ｋは低級アルキルまたはアラルキルを意味する
〕
で示されるし一アスコルビン酸誘導体の収率の良好な新
規製法を提供することを目的とする。! The present invention includes the 3-0-methyl and 3-0-benzyl derivatives, and the yield of mono-ascorbic acid derivatives represented by the formula: The purpose is to provide a good new manufacturing method.
本発明によれは式〔■〕の化合物（Ａつぎの反応式１に
従って製造される。According to the present invention, a compound of formula [■] (A) is produced according to the following reaction formula 1.
反応式１
〔式中、ｋは前記と同じである〕
この反応式に従い、５および６位のヒドロキシ基が保護
された式ＣＩＩ）で示される３−０−アルキルもしくは
アラルキル−５，６−０−イソプロピリデン−し−アス
コルビン酸の５．６−０−インプロピリデン保護基を脱
離させて所望の式〔■〕の化合物を得る。Reaction formula 1 [wherein k is the same as above] According to this reaction formula, 3-0-alkyl or aralkyl-5,6-0 represented by formula CII) in which the hydroxy groups at the 5 and 6 positions are protected The 5,6-0-inpropylidene protecting group of -isopropylidene-di-ascorbic acid is removed to obtain the desired compound of formula [■].
この保護基の脱離は生成物の分解を起さないような温和
な酸性条件下で行なわれ、好ましくは、式Ｃ■〕の化合
物を含水酢酸中、９０〜１００°Ｃて１５〜４５分間加
熱することにより行なわれる。This removal of the protecting group is carried out under mild acidic conditions that do not cause decomposition of the product, and preferably the compound of formula C) is dissolved in aqueous acetic acid at 90 to 100°C for 15 to 45 minutes. This is done by heating.
所望の式ＣＩ）の生成物は常法によって反応混合液から
精製、単離することかでき、例えは、溶媒を留去し、再
結晶を行なう。The desired product of formula CI) can be purified and isolated from the reaction mixture by conventional methods, for example by distilling off the solvent and carrying out recrystallization.
式〔■〕の化合物は、つぎの反応式２に従って製造され
る。The compound of formula [■] is produced according to Reaction Formula 2 below.
反応式２
％式％）
〔式中、ｋは前記と同じ、Ｘは塩素、臭素、ヨウ素のよ
うなハロゲンを意味する〕
この反応式に従い、式〔■１〕て示される５、６−０−
インプロピリデン−Ｌ−アスコルビン酸をハロゲン化ア
ルキルもしくはアラルキルと反応させると式しＩＩ ’
１１で示される３−０−アルキルもしくはアラルキル−
５，６−０−インプロピリデン−Ｉ−一アスコルビン酸
が得られる。Reaction formula 2 % formula %) [In the formula, k is the same as above, X means halogen such as chlorine, bromine, iodine] According to this reaction formula, 5,6-0 shown as formula [■1] −
When impropylidene-L-ascorbic acid is reacted with an alkyl or aralkyl halide, the formula II'
3-0-alkyl or aralkyl- represented by 11
5,6-0-impropylidene-I-monoascorbic acid is obtained.
この反応はヒドロキシ基を有しない極性溶媒、すなわち
、非ヒドロキシ溶媒中、アルカリの存在下、１０〜３０
°Ｃで１〜７２時間行なう。This reaction is carried out in a polar solvent having no hydroxyl group, i.e., a non-hydroxyl solvent, in the presence of an alkali, for 10 to 30
Perform for 1-72 hours at °C.
Ｌ−アスコルビン酸のアルキル化またはアラルキル化反
応においては溶媒の選択が非常に重要でアリ、水、アル
コールなどのヒドロキシ基を有する溶媒では多種の生成
物を生じ、また、分解反応が起るために目的とする３−
０−アルキルまたはアラルキル体がほとんど得られない
。したがって、アセトン、ジメチルホルムアミド、ジメ
チルスルホキシド、テトラヒドロフランのような非ヒド
ロキシ溶媒を用いることが望ましく、実用上、ことにジ
メチルスルホキシドが好ましい。In the alkylation or aralkylation reaction of L-ascorbic acid, the selection of the solvent is very important. Solvents with hydroxyl groups such as ants, water, and alcohol produce various products and also cause decomposition reactions. Objective 3-
Almost no 0-alkyl or aralkyl bodies are obtained. Therefore, it is desirable to use a non-hydroxy solvent such as acetone, dimethylformamide, dimethylsulfoxide, or tetrahydrofuran, with dimethylsulfoxide being particularly preferred in practice.
また、アルカリの選択も重要で、炭酸アルカリや、それ
より強いアルカリを用いると２，３−ジアルキルもしく
はジアラルキル体が副生ずる。したがって、該アルカリ
としては重炭酸ナトリウムのような重炭酸アルカリを用
いることか好ましい。The selection of the alkali is also important; if an alkali carbonate or a stronger alkali is used, a 2,3-dialkyl or dialkyl compound will be produced as a by-product. Therefore, it is preferable to use an alkali bicarbonate such as sodium bicarbonate as the alkali.
この反応にあける式［ＩＩＩ ）の化合物と式ＲＸて示
されるハロゲン化アルキルもしくはアラルキルの使用割
合は特に限定するものではないか、通常、式ＣＩｆｆ
）の化合物１モルに対し、ハロゲン化アルキルもしくは
アラルキルを０．１〜２０倍モル用いることが好ましい
。また、アルカリは式〔■〕の化合物に対して等モル以
上用いることが好ましい。The proportion of the compound of formula [III) and the alkyl halide or aralkyl represented by formula RX used in this reaction is not particularly limited, and usually the compound of formula CIff is used.
) It is preferable to use 0.1 to 20 times the mole of the alkyl halide or aralkyl per mole of the compound. Further, it is preferable to use the alkali in an amount equal to or more than the same mole relative to the compound of formula [■].
式〔■〕の化合物は公知の方法に従って、Ｌ−アスコル
ビン酸から得られる。The compound of formula [■] can be obtained from L-ascorbic acid according to known methods.
式ＣＩ）の化合物中、ｋがメチルまたはベンジル以外の
化合物は文献末記載の新規化合物であり、それらも本発
明範囲のものである。Among the compounds of formula CI), compounds in which k is other than methyl or benzyl are novel compounds described at the end of literature, and they are also within the scope of the present invention.
式〔■〕のＬ−アスコルビン酸誘導体はきわめて安定で
あり、中性〜塩基性条件下、３７°Ｃてもほとんど分解
されず、また、その構造の主要部が天然物であるため、
毒性はほとんど認められず、医薬品、化粧品、口腔剤へ
配合する薬効剤としてきわめて適したものである。The L-ascorbic acid derivative of formula [■] is extremely stable and hardly decomposes even at 37°C under neutral to basic conditions, and since the main part of its structure is a natural product,
Almost no toxicity is observed, making it extremely suitable as a medicinal agent for use in pharmaceuticals, cosmetics, and oral preparations.
つきに参考例および実施例を挙げて本発明をさらに詳し
く説明する。The present invention will now be described in more detail with reference to Reference Examples and Examples.
参考例
■−−アスコルビン酸２ Ｏｆ （１１３，６ミリモル
）をアセトン９０ｄに加え、この混合液に塩化アセチル
２．５ｇ？（３５，０ミリモル）を加え、２５〜３０゛
Ｃで攪拌する。反応の進行とともに５．６−０−イソプ
ロピリデン−Ｌ−アスコルビン酸が析出してくる。２時
間後、反応混合液から析出した結晶を戸数し、アセトン
−ヘキサン（４ニア）で洗浄して白色結晶の５．６−０
−インプロピリデン−１゜−アスコルビン酸１９．９４
９ （収率８１％）ヲ得る。これをアセトンから再結晶
させて精製５．６−〇−イソプロピリデンーし一アスコ
ルビン酸９．６５ｇ（収率３９％）を得る。Reference example ■--Ascorbic acid 2Of (113.6 mmol) was added to 90 d of acetone, and 2.5 g of acetyl chloride was added to this mixture. (35.0 mmol) and stirred at 25-30°C. As the reaction progresses, 5.6-0-isopropylidene-L-ascorbic acid precipitates. After 2 hours, the crystals precipitated from the reaction mixture were separated and washed with acetone-hexane (4N) to give white crystals of 5.6-0.
-Impropylidene-1°-ascorbic acid 19.94
9 (yield 81%) was obtained. This is recrystallized from acetone to purify 5.6-0-isopropylidene to obtain 9.65 g (yield 39%) of monoascorbic acid.
融点：２０６〜２０８”Ｃ（分解）
ＩＲ：１６６７．１７５７α−１
Ｕ■：λ ２４５．Ｏｌｏｇε−４，００（メタａｘ
ノール）
〔α〕２９：＋９° （ｃ ＝ １．０’Ｏ、メタノー
ル）実施例１
５．６−０−イソプロピリデン−し−アスコルビン酸１
ｉｉ１（４，６３ミリモル）をジメチルスルホキシド５
ｙｎｉに溶解し、この溶液に重炭酸ナトリウム０．３９
９Ｃ４，６ミｌ）モル）を加えて攪拌する。ついで、ヨ
ウ化メチル１．４４ｔｘｔ （２３，２モル）を加え、
２５°Ｃで攪拌する。反応の進行をシリカゲル薄層クロ
マトクラフィー（展開溶媒：ベンゼンー酢酸エチル（２
：１））で調べる。２時間後、反応混合液を濾過しで重
炭酸ナトリウムを除去し、ｐ液にベンゼン１００ｒｔｔ
ｔを加え、水２０ｍ１で３回、ついで、飽和食塩水２０
＊ｔて３回洗浄する。ベンゼン層を無水硫酸ナトリウム
で乾燥する。−夜放り後、ベンゼンを留去して黄色透明
油、状の３−〇−メチルー５．６−０−イソプロピリデ
ン−し−アスコルビン酸０．２：Ｍ（収率２１，６％）
を得る。Melting point: 206-208"C (decomposition) IR: 1667.1757α-1 U■:λ 245.Ologε-4,00 (methaxnol) [α]29: +9° (c = 1.0'O, methanol ) Example 1 5.6-0-isopropylidene-di-ascorbic acid 1
ii1 (4.63 mmol) in dimethyl sulfoxide 5
yni and add 0.39% sodium bicarbonate to this solution.
Add 9C (4.6 ml) mole) and stir. Then, 1.44 txt (23.2 mol) of methyl iodide was added,
Stir at 25°C. The progress of the reaction was monitored by silica gel thin layer chromatography (developing solvent: benzene-ethyl acetate (2
:1)). After 2 hours, the reaction mixture was filtered to remove the sodium bicarbonate, and the p-liquid was added with 100 rtt of benzene.
Add t, add 20ml of water 3 times, then add 20ml of saturated saline.
*Wash 3 times. Dry the benzene layer with anhydrous sodium sulfate. -After standing overnight, benzene was distilled off to give a yellow transparent oil of 3-0-methyl-5.6-0-isopropylidene-ascorbic acid 0.2:M (yield 21.6%)
get.
ＩＲ：１７０１．１７７０ｍ−１
Ｕｖ：λｍａｘ ２４５．０ ｌｏｇε−３，９５（
メタノール）
〔α〕２９：４３２°（ｃ＝１．１６．クロロホルム）
１）
得られた３−０−メチル−５，６−０−イソプロピリデ
ン−Ｌ−アスコルビン酸５００１ｎｇに５０％酢酸１１
＊ｔを加え、水浴上、９５〜１００°Ｃで２０分間加熱
する。反応混合液から溶媒を留去して３−０−メチル−
Ｌ−アスコルビン酸を得る。IR:1701.1770m-1 Uv:λmax 245.0 logε-3,95(
methanol) [α]29:432° (c=1.16.chloroform)
1) Add 50% acetic acid 11 to 5001 ng of the obtained 3-0-methyl-5,6-0-isopropylidene-L-ascorbic acid.
*Add and heat on a water bath at 95-100°C for 20 minutes. The solvent was distilled off from the reaction mixture to give 3-0-methyl-
Obtain L-ascorbic acid.
実施例２
５．６−０−イソプロピリデン−し−アスコルビン酸４
Ｍ（２３，１５ミリモル）をジメチルスルホキシド２５
＊ｔに溶解する。この溶液に重炭酸ナトリウム１．９５
ｇ（２３，１５ミリモル）を加え、攪拌する。ついで、
臭化エチル９ｇ／（１２４ミ’Ｊモル）を加え、２５゛
Ｃで攪拌する。２４時間後、反応混合液を濾過し、Ｆ液
にベンゼン３００ ｙｔｉヲ加え、飽和食塩水１００耐
で３回洗浄する。有機層を水性層から分離し、無水硫酸
ナトリウムで乾燥する。ベンゼンを留去して３−０−エ
チル−５，６−〇−イソプロピリデンーし一アスコルビ
ン酸の黄白色結晶２．３Ｅｌ（収率４２％）を得る。Example 2 5.6-0-isopropylidene-di-ascorbic acid 4
M (23.15 mmol) in dimethyl sulfoxide 25
*Soluble in t. Add 1.95 ml of sodium bicarbonate to this solution.
g (23.15 mmol) and stir. Then,
Add 9 g/(124 mmol) of ethyl bromide and stir at 25°C. After 24 hours, the reaction mixture is filtered, 300 g of benzene is added to solution F, and the mixture is washed three times with 100 g of saturated saline. The organic layer is separated from the aqueous layer and dried over anhydrous sodium sulfate. Benzene was distilled off to obtain 2.3 El of yellow-white crystals of 3-0-ethyl-5,6-0-isopropylidene-monoscorbic acid (yield: 42%).
融点：１０７〜１０７．５°Ｃ（ベンゼンより再結晶）
ＩＲＫＢｒ：１７０２，１７７２ｃｍ−１Ｕｖ：λｍａ
！２４５．８ １ｏｇｇ ＝４．０４（メタノール）
〔α〕２９：＋２３°（Ｃ＝１．０．クロロホルム）ｌ
）
得られた３−０−エチル−５，６−０−イソプロピリデ
ン−し−アスコルビン酸５００１ｑ（２，０５ミリモル
）に５０％酢酸１１＊ｔを加え、水浴上、９５〜１００
”Ｃ：で２０分間加熱する。反応混合液から溶媒を留
去して３−ｏ−エチル−Ｌ−アスコルビン酸の白色結晶
を得、酢酸エチルから再結晶させる（装置３４３〜、収
率８２％）。Melting point: 107-107.5°C (recrystallized from benzene) IRKBr: 1702, 1772 cm-1Uv: λma
! 245.8 1 ogg = 4.04 (methanol) [α] 29: +23° (C = 1.0. chloroform) l
) 11*t of 50% acetic acid was added to 5001q (2.05 mmol) of the obtained 3-0-ethyl-5,6-0-isopropylidene-ascorbic acid, and the mixture was heated on a water bath at 95-100 ml.
"C: for 20 minutes. The solvent is distilled off from the reaction mixture to obtain white crystals of 3-o-ethyl-L-ascorbic acid, which is recrystallized from ethyl acetate (apparatus 343~, yield 82%. ).
融点：１１１．５〜１１２．５°Ｃ
ＩＲＫＢ、：１６９２，１７４９ａ−１実施例３
５．６−０−イソプロピリデン−し−アスコルビン酸１
１（４，６３ミリモル）をジメチルスルホキシド５Ｍｔ
に溶解し、この溶液に重炭酸ナトリウム０．３９９ （
４，６ミＩＪモル）を加えて攪拌する。ついで、臭化イ
ソプロピル２．１ ’ＩＷＩｅＣ２３ミリモル）を加え
、２５゛Ｃで攪拌する。反応の進行をシリカゲル薄層ク
ロマトグラフィ＝（展開溶媒：ベンゼンー酢酸エチル（
２：１）、検出：紫外線ランプ、２０％エタノール性リ
ンモリブデン酸）で調べる。２４時間後、反応混合液を
耐過して重炭酸ナトリウムを除去し、Ｆ液にベンゼン１
００ｒ／を加える。水５ＣＪｘｔで２回、ついで、飽和
食塩水５０ｐｔｌで２回洗浄し、無水硫酸ナトリウムで
乾燥する。−夜放置後、ベンゼンを留去して淡黄色油状
の３−〇−インプロピルー５．６−０−イソプロピリデ
ン−し−アスコルビン酸０．１７ｇ（収率９６％）を得
る。ベンゼンより再結晶し、白色結晶を得る。Melting point: 111.5-112.5°C IRKB: 1692,1749a-1 Example 3 5.6-0-isopropylidene-shi-ascorbic acid 1
1 (4.63 mmol) in dimethyl sulfoxide 5Mt
Dissolve in this solution 0.399% sodium bicarbonate (
4.6 mmol) and stir. Then, 2.1'IWIeC (23 mmol) of isopropyl bromide was added and stirred at 25°C. Progress of the reaction was monitored by silica gel thin layer chromatography = (developing solvent: benzene-ethyl acetate (
2:1), detection: ultraviolet lamp, 20% ethanolic phosphomolybdic acid). After 24 hours, the reaction mixture was passed through to remove the sodium bicarbonate and Part F was added with 1 lb of benzene.
Add 00r/. Wash twice with 5 CJxt of water, then twice with 50 ptl of saturated saline, and dry over anhydrous sodium sulfate. - After standing overnight, benzene was distilled off to obtain 0.17 g (yield 96%) of 3-0-inpropyl-5.6-0-isopropylidene-ascorbic acid as a pale yellow oil. Recrystallize from benzene to obtain white crystals.
融点＝８０〜８１．５℃
ＩＲ：１７０１．１７６８ｃＭ−１
ＵＶ、λｍａ）（２４６，４ｌｏｇε；３８５〔α〕曾
：斗１８°（Ｃ＝１．８４．−メタノール）得られた３
−０−イソプロピル−５，６−０−インプロピリデン−
Ｌ−アスコルビン酸５００〜に５０％酢酸１１ｓｒ？を
加え、水浴上、９５〜１００゛Ｃで３０分間加熱する。Melting point = 80-81.5°C IR: 1701.1768 cM-1 UV, λma) (246,4 log ε; 385 [α] so: 18° (C = 1.84.-methanol) Obtained 3
-0-isopropyl-5,6-0-inpropylidene-
L-ascorbic acid 500 ~ 50% acetic acid 11sr? and heat on a water bath at 95-100°C for 30 minutes.
反応混合液から溶媒を留去して３−０−イソプロピル−
Ｌ−アスコルビン酸を得る。The solvent was distilled off from the reaction mixture to give 3-0-isopropyl-
Obtain L-ascorbic acid.
融点：１１１〜１１３°Ｃ
ＩＲＫＢｒ ：１６８０，１７６０ｃ’ｍ−１〔α〕甘
せ＋４１°（Ｃ＝０．５．メタノール）実施例４
５．６−０−（ソプロピリデンーし一アスコルビン酸５
１Ｆ（２３，１５ミリモル）をジメチルスルホキシド２
０ｍ１に溶解し、これに重炭酸ナトリウム１．９５ｇ（
２３，１５ミリモル）を加え、攪拌する。Melting point: 111-113°C IRKBr: 1680, 1760 c'm-1 [α] Sweet + 41° (C = 0.5. Methanol) Example 4 5.6-0-(Sopropylidene-mono-ascorbic acid 5
1F (23.15 mmol) in dimethyl sulfoxide 2
1.95 g of sodium bicarbonate (
23.15 mmol) and stir.
ついで、塩化ベンジル１ｍ１（７，１９ミＩＪモル）を
加え、２５゛Ｃで攪拌する。反応の進行をシリカゲル薄
層クロマトグラフィー（展開溶媒：ベンゼンー酢酸エチ
ル（２：１）、検出：紫外線ランプ、２０％エタノール
性リンモリブデン酸）で調べる。Then 1 ml (7.19 mmol) of benzyl chloride is added and stirred at 25°C. The progress of the reaction is examined by silica gel thin layer chromatography (developing solvent: benzene-ethyl acetate (2:1), detection: ultraviolet lamp, 20% ethanolic phosphomolybdic acid).
４８時間後、重炭酸す） ＩＪウムをＦ去し、Ｆ液にベ
ンゼン１００＊ｔ′を加える。ベンゼン層ヲ水３０１１
１１で３同、ついで、飽和食塩水５０Ｍ１で２回洗浄す
る。ベンゼン層を無水硫酸ナトリウムで乾燥Ｔる。−夜
放置後、無水硫酸ナトリウムを戸去し、Ｆ液よりベンゼ
ンを留去して３−０−ベンジル−５，６−０−インプａ
ビリデン−Ｌ−アスコルビン酸の白褐色結晶を得、ベン
ゼンから再結晶させる（収量４５０ｑ、塩化ベンジルか
らの収率３４％）。After 48 hours, remove the bicarbonate (IJ) and add 100*t' of benzene to the F solution. Benzene layer water 3011
11 three times, and then twice with saturated saline 50M1. The benzene layer was dried with anhydrous sodium sulfate. -After standing for the night, remove the anhydrous sodium sulfate, distill off the benzene from the F solution, and make 3-0-benzyl-5,6-0-impa.
White-brown crystals of pylidene-L-ascorbic acid are obtained and recrystallized from benzene (yield 450 q, yield 34% from benzyl chloride).
融点：１１０〜１１１°Ｃ
ＩＲ： １６９５．１７６４ｃＩＩＩ−’Ｕｖ：λｍａ
ｘ ２０８．０ 、２４６．４ ｌｏｇε＝３．９〔
α〕２ｏ９：＋２２°（ｃ＝１．１４．メタノール）得
られた３−０−ベンジル−５，６−０−イソプロピリデ
ン−し−アスコルビン酸５００１ｑに５０％酢酸１１１
１ｔを加え、水浴上、９５〜１ｏｏ′ｃで２０分間加熱
する。反応混合液から溶媒を留去して油状の３−〇−ベ
ンジルーし一アスコルビン酸を得る。Melting point: 110-111°C IR: 1695.1764cIII-'Uv: λma
x 208.0, 246.4 logε=3.9 [
α]2o9: +22° (c=1.14.methanol) 50% acetic acid 111 to 5001q of the obtained 3-0-benzyl-5,6-0-isopropylidene-ascorbic acid
Add 1 t and heat on a water bath at 95-1 oo'c for 20 minutes. The solvent is distilled off from the reaction mixture to obtain oily 3-0-benzyl-mono-ascorbic acid.
ＩＲ： １６９０．１７５０ｃＮ−’
〔α’：１２ｏ９：＋１２°（Ｃ＝０．５．メタノール
）特許出願人 サンスター株式会社 ほか１名代理人弁
理士 青 山 −葆ほか２名IR: 1690.1750cN-'[α': 12o9: +12° (C=0.5.methanol) Patent applicant: Sunstar Co., Ltd. and 1 other representative patent attorney: Aoyama - Aoyama and 2 others
Claims (1)
〕 で示される化合物の５．６−０−インプロピリデン保護
基を脱離させることを特徴とする式：％式％ 〔式中、ｋは１り記と同じである〕 で示される化合物の製法。 （２）式（ＩＩＩの化合物を含水酢酸中、９０〜１０（
３）式二 １−１０ ０８ て示される化合物を、アルカリの存在下、非ヒドロキシ
溶媒中、式： 〔式中、ｋは低級アルキルまたはアラルキル、Ｘはハロ
ゲンを意味する〕 で示されるハロゲン化アルキルもしくはアラルキルと反
応させて式： ％式％ 〔式中、ｋは前記と同じである〕 で示される化合物を得、ついで、その５．６−０−イン
プロピリデン保護基を脱離させることを特徴とする式： ％式％ 〔式中、ｋは前記と同じである〕 で示される化合物の製法。 （４）式Ｃｌｌの化合物とハロゲン化アルキルもしくは
アラルキルとの反応をジメチルスルホキンド中、重炭酸
アルカリの存在下に行なう前記第（３）項の製法。[Claims] (1) Formula: [In the formula, R means lower alkyl or aralkyl] 5.6-0-Impropylidene protecting group of the compound is removed. A method for producing a compound represented by the formula: % Formula % [In the formula, k is the same as in item 1]. (2) A compound of formula (III) was dissolved in acetic acid containing 90 to 10 (
3) A compound represented by the formula 21-10 08 is added to an alkyl halide represented by the formula: [wherein k means lower alkyl or aralkyl, and X means halogen] in the presence of an alkali in a non-hydroxy solvent. Or react with aralkyl to obtain a compound represented by the formula: % formula % [wherein k is the same as above], and then remove the 5,6-0-inpropylidene protecting group. Characteristic formula: % Formula % [In the formula, k is the same as above] A method for producing a compound represented by the following formula. (4) The method according to item (3) above, wherein the reaction of the compound of formula Cll with an alkyl halide or an aralkyl halide is carried out in dimethylsulfokind in the presence of an alkali bicarbonate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP56156860A JPS5857373A (en) | 1981-10-01 | 1981-10-01 | Preparation of l-ascorbic acid derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP56156860A JPS5857373A (en) | 1981-10-01 | 1981-10-01 | Preparation of l-ascorbic acid derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS5857373A true JPS5857373A (en) | 1983-04-05 |
Family
ID=15636959
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP56156860A Pending JPS5857373A (en) | 1981-10-01 | 1981-10-01 | Preparation of l-ascorbic acid derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5857373A (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61207312A (en) * | 1985-03-11 | 1986-09-13 | Kanebo Ltd | Skin-beautifying cosmetic |
| WO1986006720A1 (en) * | 1985-05-17 | 1986-11-20 | Takeda Chemical Industries, Ltd. | Ascorbic acid derivatives, production thereof, and pharmaceutical preparation therefrom |
| WO1986007592A1 (en) * | 1985-06-18 | 1986-12-31 | Takeda Chemical Industries, Ltd. | Ascorbic acid derivatives, process for their preparation, and preparations containing same |
| JPH01228977A (en) * | 1988-03-09 | 1989-09-12 | Nippon Hai Potsukusu:Kk | Ascorbic acid derivative, production thereof and antioxidant comprising said derivative |
| WO1999050258A1 (en) * | 1998-03-27 | 1999-10-07 | Lg Chemical Ltd. | Polyethoxylated ascorbic acid derivatives as a novel antioxidant and process for preparing thereof |
| KR100761959B1 (en) | 2006-10-12 | 2007-10-04 | (주)코스몰 | Method for preparating crystalline 3-o-alkyl-ascorbic acid |
| CN105367524A (en) * | 2015-06-19 | 2016-03-02 | 上海珈叶实业有限公司 | Preparation method of 3-O-alkyl ascorbic acid |
| US10322078B2 (en) | 2014-06-10 | 2019-06-18 | Ajinomoto Co., Inc. | Cosmetic composition containing 3-O-alkyl-L-ascorbic acid or salt thereof |
-
1981
- 1981-10-01 JP JP56156860A patent/JPS5857373A/en active Pending
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61207312A (en) * | 1985-03-11 | 1986-09-13 | Kanebo Ltd | Skin-beautifying cosmetic |
| WO1986006720A1 (en) * | 1985-05-17 | 1986-11-20 | Takeda Chemical Industries, Ltd. | Ascorbic acid derivatives, production thereof, and pharmaceutical preparation therefrom |
| WO1986007592A1 (en) * | 1985-06-18 | 1986-12-31 | Takeda Chemical Industries, Ltd. | Ascorbic acid derivatives, process for their preparation, and preparations containing same |
| JPH01228977A (en) * | 1988-03-09 | 1989-09-12 | Nippon Hai Potsukusu:Kk | Ascorbic acid derivative, production thereof and antioxidant comprising said derivative |
| WO1999050258A1 (en) * | 1998-03-27 | 1999-10-07 | Lg Chemical Ltd. | Polyethoxylated ascorbic acid derivatives as a novel antioxidant and process for preparing thereof |
| US6444144B1 (en) * | 1998-03-27 | 2002-09-03 | Lg Chemical Ltd. | Polyethoxylated ascorbic acid derivatives as a novel antioxidant and process for preparing thereof |
| KR100761959B1 (en) | 2006-10-12 | 2007-10-04 | (주)코스몰 | Method for preparating crystalline 3-o-alkyl-ascorbic acid |
| US7838690B2 (en) | 2006-10-12 | 2010-11-23 | Cosmol Co. Ltd | Method for preparing crystalline 3-0-alkyl-ascorbic acid |
| US10322078B2 (en) | 2014-06-10 | 2019-06-18 | Ajinomoto Co., Inc. | Cosmetic composition containing 3-O-alkyl-L-ascorbic acid or salt thereof |
| CN105367524A (en) * | 2015-06-19 | 2016-03-02 | 上海珈叶实业有限公司 | Preparation method of 3-O-alkyl ascorbic acid |
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