JP2620251B2 - Method for producing chroman derivative - Google Patents
Method for producing chroman derivativeInfo
- Publication number
- JP2620251B2 JP2620251B2 JP62225863A JP22586387A JP2620251B2 JP 2620251 B2 JP2620251 B2 JP 2620251B2 JP 62225863 A JP62225863 A JP 62225863A JP 22586387 A JP22586387 A JP 22586387A JP 2620251 B2 JP2620251 B2 JP 2620251B2
- Authority
- JP
- Japan
- Prior art keywords
- mmol
- compound
- reaction
- added
- formula
- 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 - Lifetime
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
- Pyrane Compounds (AREA)
Description
【発明の詳細な説明】 〔産業上の利用分野〕 本発明は、光学活性α−トコフェロールを製造するた
めに有用な中間体であるクロマン誘導体の製造方法に関
する。Description: TECHNICAL FIELD The present invention relates to a method for producing a chroman derivative which is an intermediate useful for producing optically active α-tocopherol.
ｄ−α−トコフェロールは、天然に広く分布している
ビタミンＥの最も代表的なもので、そのもの自体のみな
らず各種の誘導体は、医薬品、食品、飼料などとして広
く汎用されており、ビタミンＥの中でも極めて重要な物
質である。d-α-Tocopherol is the most representative of vitamin E widely distributed in nature, and various derivatives as well as itself are widely used as pharmaceuticals, foods, feeds, and the like. Among them, it is a very important substance.
しかしながら、ｄ−α−トコフェロールは天然物、主
として植物油から単離しなければならず、工業的に大量
生産するには適さない。即ち、植物油中のｄ−α−トコ
フェロールの含量は極めて少量であるために極めて多量
の植物油を必要とし、しかもβ，γ，δ−体などの同族
体との分離精製が必要であり、単離にも困難を伴うとい
う欠点がある。However, d-α-tocopherol must be isolated from natural products, mainly vegetable oils, and is not suitable for industrial mass production. That is, since the content of d-α-tocopherol in vegetable oil is extremely small, an extremely large amount of vegetable oil is required, and further, separation and purification from homologues such as β, γ, δ-forms are required. Also has the drawback of being difficult.
そこで、光学活性α−トコフェロール、殊にｄ−α−
トコフェロールを化学的に合成しようとする試みは種々
なされている（例えばH.Mayer,O.Islerら,Helv.Chim.Ac
ta,46,650（1963）;J.W.Scott,F.T.Bizzarro,D.R.Parri
sh,G.Saucy,Helv.Chim.Acta,59,290（1976）;K.K.Chan,
N.Cohenら,J.Org.Chem.41,3497,3512（1976），43,3435
（1978）など）が、工業的に有用な方法は皆無である。Therefore, optically active α-tocopherol, especially d-α-
There have been various attempts to chemically synthesize tocopherol (eg, H. Mayer, O. Isler et al., Helv. Chim. Ac.
ta, 46, 650 (1963); JWScott, FTBizzarro, DRParri
sh, G. Saucy, Helv. Chim. Acta, 59, 290 (1976); KKChan,
N. Cohen et al., J. Org. Chem. 41 , 3497, 3512 (1976), 43 , 3435.
(1978)), but there is no industrially useful method.
即ち、従来提案されている方法はすべて何れかの時点
において中間物質でd1体の光学分割を必要とする。この
光学分割が必要であることは、この分割により収率が30
〜40％と大幅にダウンするという大きな欠点があり、工
業的な方法とは言い難い。In other words, all of the conventionally proposed methods require optical resolution of the d1 body with an intermediate substance at any time. The necessity of this optical resolution means that the yield is 30
There is a major drawback that it is down to about 40%, which is not an industrial method.
そこで本発明者等は、d1体の光学分割を必要としない
方法について長年研究を重ねた結果、次に示す方法によ
り、このことが可能であることを見出し、ここに本発明
を完成するに至った。Thus, the present inventors have conducted long-term studies on a method that does not require optical division of the d1 body.As a result, the present inventors have found that this method can be performed by the following method, and have completed the present invention. Was.
即ち、原料として（Ｓ）−シトラマル酸を用いて、ｄ
−α−トコフェロールを製造する際の中間体である次に
示される化合物（Ｉ）を製造する。That is, using (S) -citramalic acid as a raw material, d
Compound (I) shown below, which is an intermediate in producing -α-tocopherol, is produced.
〔第一工程〕 （Ｓ）−シトラマル酸から得られた光学活性スルフィ
ド（II）と、置換フェノール（III）とを、〔2.3〕シグ
マトロピー転位反応を行い、転位生成物（IV）を得る工
程である。式（III）のＸは水酸基の保護基を示すが、
通常アセチル、プロピオニル、ピバロイルなどのアシル
基、メチル、エチル、プロピルなどのアルキル基、テト
ラヒドロピラニル、メトキシメチル基などがあげられる
が、最も好ましいものはアセチル基である。 [First Step] In the step of subjecting an optically active sulfide (II) obtained from (S) -citramalic acid and a substituted phenol (III) to [2.3] a sigmatropic rearrangement reaction to obtain a rearranged product (IV). is there. X in the formula (III) represents a protecting group for a hydroxyl group,
Usually, an acyl group such as acetyl, propionyl and pivaloyl, an alkyl group such as methyl, ethyl and propyl, a tetrahydropyranyl and a methoxymethyl group are exemplified, and the most preferred one is an acetyl group.
本反応は〔2.3〕シグマトロピー転位反応によるが、
通常の方法としては、塩化メチレンを溶媒として用い、
−40℃前後で塩化スルフリウ（SO2Cl2）を作用させ、次
いでトリエチルアミンを作用させて転位反応を行う。This reaction is based on [2.3] sigmatropic rearrangement reaction,
The usual method is to use methylene chloride as the solvent,
At around −40 ° C., sulfuryl chloride (SO 2 Cl 2 ) is acted on, and then triethylamine is acted on to effect a rearrangement reaction.
本反応は得られた転位生成物（IV）を還元的に脱硫
し、脱保護した後、環化して目的物質（Ｉ）を得る工程
である。This reaction is a step of reductively desulfurizing the obtained rearrangement product (IV), deprotecting, and then cyclizing to obtain the target substance (I).
本反応は、まず、例えばラネーニッケル（Raney Ni）
を用いて、還元的に脱硫反応を行い、次いで、例えばLi
AlH4を用いて脱保護を行い環化せしめて目的物質を得て
もよいし、一挙にラネーニッケルと還元剤を用いて目的
物質（Ｉ）を得てもよい。In this reaction, first, for example, Raney Ni
Using a reductive desulfurization reaction, and then, for example, Li
The target substance may be obtained by deprotection and cyclization using AlH 4 , or the target substance (I) may be obtained at once using Raney nickel and a reducing agent.
ラネーニッケルのみを用いて脱硫反応を行えば、次の
化合物が一旦得られる。If the desulfurization reaction is performed using only Raney nickel, the following compound is obtained once.
上記の化合物（Ｖ）を単離して後、環化反応を行うこ
とは勿論可能である。 After isolating the above compound (V), it is of course possible to carry out a cyclization reaction.
第一工程で用いられる光学活性スルフィド（II）は、
例えば次の方法によって得ることができる。The optically active sulfide (II) used in the first step is
For example, it can be obtained by the following method.
具体的に示せば次の通りである。 The details are as follows.
〔第三工程〕 （Ｓ）−シトラマル酸から誘導された（Ｓ）−シトラ
マル酸ジメチル（VI）を、例えばLiAlH4で還元し、トリ
オール（VII）を得る工程である。この際の溶媒として
は、例えばテトラヒドロフラン（THF）などを用いるこ
とができる。 [Third Step] In this step, dimethyl (S) -citramalate (VI) derived from (S) -citramalic acid is reduced with, for example, LiAlH 4 to obtain triol (VII). As the solvent at this time, for example, tetrahydrofuran (THF) or the like can be used.
トリオール（VII）を、アセトニドアルコール（VII
I）とする工程である。Triol (VII) is replaced with acetonide alcohol (VII
This is the step I).
本反応は、トリオール（VII）と、2,2−ジメトキシプ
ロパンとをトルエンスルホン酸の存在下で反応せしめる
ことによって得られる。この際、溶媒としては、例えば
アセトンなどを用いることができる。This reaction is obtained by reacting triol (VII) with 2,2-dimethoxypropane in the presence of toluenesulfonic acid. At this time, for example, acetone or the like can be used as the solvent.
第四工程で得られたアセトニドアルコールをトシル化
した後、イソプロピルチオールと反応させ、光学活性ス
ルフィド（II）を得る工程である。トシル化する場合
は、例えばピリジンなどの溶媒中、ｐ−トルエンスルホ
ニルクロライドを添加して反応を行う。In this step, the acetonide alcohol obtained in the fourth step is tosylated and then reacted with isopropylthiol to obtain an optically active sulfide (II). In the case of tosylation, for example, p-toluenesulfonyl chloride is added in a solvent such as pyridine to carry out the reaction.
次いで、例えば金属ナトリウムの存在下にイソプロピ
ルチオール（イソプロピルメルカプタン）を上記で得ら
れたトシルエステルに添加して、目的物質であるスルフ
ィド体（II）を得る。Next, for example, isopropyl thiol (isopropyl mercaptan) is added to the tosyl ester obtained above in the presence of sodium metal to obtain a sulfide form (II) as a target substance.
本発明によって得られたクロマン化合物（Ｉ）は、例
えば次の方法（既知）によりｄ−α−トコフェロールと
することができる。The chroman compound (I) obtained by the present invention can be converted into d-α-tocopherol by, for example, the following method (known).
以上本発明方法を詳細に説明したが、本発明方法にお
ける中間体はそれぞれ新規化合物であると考えられる。 Although the method of the present invention has been described in detail above, each of the intermediates in the method of the present invention is considered to be a novel compound.
本発明方法は、d1分割を必要とせず、工業的に高収率
で光学活性α−トコフェロールを製造できる方法であ
り、従って本発明の価値は極めて高い。The method of the present invention does not require d1 resolution, and is a method capable of industrially producing optically active α-tocopherol in a high yield. Therefore, the value of the present invention is extremely high.
以下に実施例を掲げるが、本発明がそれのみに限定さ
れることがないことはいうまでもない。Examples are given below, but it goes without saying that the present invention is not limited to them.
実施例１ （Ｓ）−６−ヒドロキシ−2,5,7,8−テトラメチルクロ
マン−２−メタノールの合成 （１）（Ｓ）−２−メチル−1,2,4−ブタントリオール
(2) 水素化リチウムアルミニウム3.08g（81.2mmol）をテ
トラヒドロフラン150ml中に懸濁させ、（Ｓ）−シトラ
マル酸(1)4.93g（33.3mmol）のテトラヒドロフラン100m
l溶液を９分間で滴下した。還流下で1.5時間反応させた
後、飽和硫酸ナトリウム水溶液20mlを５分間で加えた。
室温で1.2時間撹拌した後、一晩静置した。沈澱を吸引
濾過により除去した後、濃縮し、標題化合物2 2.37g
（収率59％）を粗生成物として得た。Example 1 Synthesis of (S) -6-hydroxy-2,5,7,8-tetramethylchroman-2-methanol (1) (S) -2-methyl-1,2,4-butanetriol
( 2 ) 3.08 g (81.2 mmol) of lithium aluminum hydride is suspended in 150 ml of tetrahydrofuran, and 4.93 g (33.3 mmol) of (S) -citramalic acid ( 1 ) in 100 m of tetrahydrofuran
The solution was added dropwise over 9 minutes. After reacting for 1.5 hours under reflux, 20 ml of a saturated aqueous sodium sulfate solution was added over 5 minutes.
After stirring at room temperature for 1.2 hours, the mixture was allowed to stand overnight. It was removed by suction filtration the precipitate, and concentrated to give the title compound 2 2.37 g
(59% yield) was obtained as a crude product.
nmr(D2O)δ； 1.07（s,3H）,1.67（t,J＝7.3Hz,2H）， 3.32（s,2H）,3.62（t,J＝7.3Hz,2H）， 4.70（s,3H） ir（neat）cm-1； 3500〜3200,2960,2650,1460,1430, 1485,1115,1060 （２）（Ｓ）−2,2,4−トリメチル−1,3−ジオキソラン
−４−エタノール(3) 化合物2の粗生成物2.12g（17.6mmol）をアセトン70ml
に溶かし、ｐ−トルエンスルホン酸一水和物14mgを加え
た。更に2,2−ジメトキシプロパン11ml（89mmol）を加
え21時間撹拌した。炭酸水素ナトリウム70mgを加えた
後、少量の水を加えた。硫酸ナトリウムにより乾燥した
後、濃縮し、粗生成物5.05gを得た。これをシリカゲル
カラムクロマトグラフィーにより精製し、標題化合物3
2.49g（収率88％）を得た。nmr (D 2 O) δ; 1.07 (s, 3H), 1.67 (t, J = 7.3 Hz, 2H), 3.32 (s, 2H), 3.62 (t, J = 7.3 Hz, 2H), 4.70 (s, 3H) ir (neat) cm -1 ; 3500-3200,2960,2650,1460,1430,1485,1115,1060 (2) (S) -2,2,4-trimethyl-1,3-dioxolan-4- Ethanol ( 3 ) A crude product of compound 2 (2.12 g, 17.6 mmol) in acetone (70 ml)
And 14 mg of p-toluenesulfonic acid monohydrate was added. Further, 11 ml (89 mmol) of 2,2-dimethoxypropane was added and the mixture was stirred for 21 hours. After adding 70 mg of sodium bicarbonate, a small amount of water was added. After drying over sodium sulfate, the mixture was concentrated to obtain 5.05 g of a crude product. This was purified by silica gel column chromatography to give the title compound 3
2.49 g (88% yield) were obtained.
nmr(CDCl3)δ； 1.26（s,3H）,1.34（s,3H）,1.41（s,3H）， 1.7〜1.9（m,2H）,2.64（s,1H）,3.44 〜3.9（m,4H） ir（neat）cm-1； 3500〜3400,3000,2950,2900,1700, 1460,1380,1250,1220,1120,1060 （３）（Ｓ）−４−（２−イソプロピルチオエチル）−
2,2,4−トリメチル−1,3−ジオキソラン(4) 化合物3 1.54g（9.61mmol）を塩化メチレン10mlに溶
かし、ピリジン2.0ml（25mmol）を加えた。０℃でｐ−
トルエンスルホニルクロライド2.6g（13.7mmol）を加え
１時間撹拌した。この混合液を冷蔵庫中で一晩静置した
後、水にあけ塩化メチレンで抽出した。洗浄（1N-HCl水
溶液、飽和NaHCO3水溶液）、乾燥（MgSO4）後、濃縮し
てトシルエステル3.29gを粗生成物として得た。nmr (CDCl 3 ) δ; 1.26 (s, 3H), 1.34 (s, 3H), 1.41 (s, 3H), 1.7 to 1.9 (m, 2H), 2.64 (s, 1H), 3.44 to 3.9 (m, 4H) ir (neat) cm -1 ; 3500-3400,3000,2950,2900,1700,1460,1380,1250,1220,1120,1060 (3) (S) -4- (2-isopropylthioethyl)-
2,2,4-trimethyl-1,3-dioxolane ( 4 ) 1.54 g (9.61 mmol) of compound 3 was dissolved in 10 ml of methylene chloride, and 2.0 ml (25 mmol) of pyridine was added. P- at 0 ° C
2.6 g (13.7 mmol) of toluenesulfonyl chloride was added and stirred for 1 hour. The mixture was allowed to stand in a refrigerator overnight, poured into water and extracted with methylene chloride. After washing (1N-HCl aqueous solution, saturated NaHCO 3 aqueous solution), drying (MgSO 4 ), and concentration, 3.29 g of tosyl ester was obtained as a crude product.
メタノール20mlに金属ナトリウム0.56g（24mmol）を
溶解させ、イソプロピルメルカプタン2.8ml（30mmol）
を加え、室温で70分間撹拌した。これに上で得たトシル
エステル3.29gのメタノール30ml溶液を滴下し、約50℃
に加熱し２時間反応させた。反応液を水にあけエーテル
抽出し、洗浄（1N-NaOH水溶液、1N-HCl水溶液）、乾燥
（MgSO4）後、濃縮し、粗生成物を得た。これをシリカ
ゲルカラムクロマトグラフィーにより精製し、標題化合
物4 1.57g（収率75％）を得た。0.56 g (24 mmol) of metallic sodium is dissolved in 20 ml of methanol, and 2.8 ml (30 mmol) of isopropyl mercaptan is dissolved.
Was added and stirred at room temperature for 70 minutes. To this was added dropwise a solution of 3.29 g of the tosyl ester obtained above in 30 ml of methanol, and the temperature was reduced to about 50 ° C.
And reacted for 2 hours. The reaction solution was poured into water, extracted with ether, washed (1N-NaOH aqueous solution, 1N-HCl aqueous solution), dried (MgSO 4 ), and concentrated to obtain a crude product. This was purified by silica gel column chromatography to give the title compound 4 1.57 g (75% yield).
nmr(CDCl3)δ； 1.26（d,J＝6.6Hz,6H）,1.29（s,3H） 1.38（s,6H）,1.82（m,2H）,2.59（m,2H）， 2.93（7-plet,J＝6.6Hz,1H）,3.72（d,J＝ 8.4Hz,1H）,3.81（d,J＝8.4Hz,1H） ir（neat）cm-1； 2975,1460,1380,1370,1240,1210, 1060,905,860,810 （２）（Ｓ）−４−〔２−（５−アセトキシ−２−ヒド
ロキシ−3,4,6−トリメチルフェニル）−２−イソプロ
ピルチオエチル〕−2,2,4−トリメチル−1,3−ジオキソ
ラン(5) トリメチルハイドロキノンモノアセテート2.67g（13.
7mmol）の塩化メチレン10ml溶液に化合物4 1.00g（4.58
mmol）を加え、更にｓ−コリジン0.8ml（6mmol）を加え
た。反応系を窒素置換し、−40℃まで冷却した後、塩化
スルフリル0.44ml（5.4mmol）を２分間で滴下した。−4
0℃で７分間撹拌した後、反応液の温度を−40℃に保ち
ながらトリエチルアミン3.7ml（27mmol）の塩化メチレ
ン3.7ml溶液を２分間で滴下した。ゆっくりと室温まで
戻した後、1N-塩酸50mlにあけ、有機層と水層を分離
し、水層を塩化メチレン抽出した後、有機層を合わせ飽
和NaHCO3水溶液で洗浄し、乾燥濃縮して粗生成物を得
た。これをシリカゲルカラムクロマトグラフィーにより
精製し、標題化合物5 0.75g（収率40％）を得た。ま
た、過剰に用いたトリメチルハイドロキノンモノアセテ
ート2.25gを回収した。消費されたトリメチルハイドロ
キノンモノアセテートを基準とする収率は84％となる。nmr (CDCl 3 ) δ; 1.26 (d, J = 6.6 Hz, 6H), 1.29 (s, 3H) 1.38 (s, 6H), 1.82 (m, 2H), 2.59 (m, 2H), 2.93 (7- plet, J = 6.6Hz, 1H), 3.72 (d, J = 8.4Hz, 1H), 3.81 (d, J = 8.4Hz, 1H) ir (neat) cm -1 ; 2975,1460,1380,1370,1240 , 1210,1060,905,860,810 (2) (S) -4- [2- (5-acetoxy-2-hydroxy-3,4,6-trimethylphenyl) -2-isopropylthioethyl] -2,2,4- Trimethyl-1,3-dioxolane ( 5 ) 2.67 g of trimethylhydroquinone monoacetate (13.
Compound 4 1.00 g (4.58
mmol) and then 0.8 ml (6 mmol) of s-collidine. After the reaction system was purged with nitrogen and cooled to -40 ° C, 0.44 ml (5.4 mmol) of sulfuryl chloride was added dropwise over 2 minutes. −4
After stirring at 0 ° C. for 7 minutes, a solution of 3.7 ml (27 mmol) of triethylamine in 3.7 ml of methylene chloride was added dropwise over 2 minutes while maintaining the temperature of the reaction solution at −40 ° C. After slowly returned to room temperature, poured into 1N- hydrochloric acid 50 ml, the organic and aqueous layers were separated, and the aqueous layer was extracted with methylene chloride, washed with saturated aqueous NaHCO 3 and the organic layers combined, dried and concentrated crude The product was obtained. This was purified by silica gel column chromatography to give the title compound 5 0.75 g (40% yield). In addition, 2.25 g of excess trimethylhydroquinone monoacetate was recovered. The yield based on consumed trimethylhydroquinone monoacetate is 84%.
nmr(CDCl3)δ； 1.10（d,J＝7Hz,3H）,1.17（s,3H）,1.25 （d,J＝7Hz,3H）,1.33（s,3H）,1.40（s, 3H）,2.02（s,3H）,2.15（s,6H）,2.29 （s,3H）,2.58（７重線,J＝7Hz,1H）,3.74 （s,2H）,4.57（t,J＝6Hz,1H）,7.93（s,1H） ir（neat）cm-1； 3250,1760,1455,1365,1240,1200, 1080,1060,905,850 （５）（Ｓ）−４−〔２−（５−アセトキシ−２−ヒド
ロキシ−3,4,6−トリメチルフェニル）エチル〕−2,2,4
−トリメチル−1,3−ジオキソラン(6) ラネーニッケル（W4）４cm3（約6g）をエタノール20m
l中にとり、化合物5 590mgのエタノール10ml溶液を加
え、２時間還流した。ニッケルを濾別した後、濃縮し、
粗生成物443mgを得た。これをシリカゲルカラムクロマ
トグラフィーにより精製し、標題化合物6 389mg（収率8
1％）を得た。nmr (CDCl 3 ) δ; 1.10 (d, J = 7Hz, 3H), 1.17 (s, 3H), 1.25 (d, J = 7Hz, 3H), 1.33 (s, 3H), 1.40 (s, 3H), 2.02 (s, 3H), 2.15 (s, 6H), 2.29 (s, 3H), 2.58 (7-fold, J = 7Hz, 1H), 3.74 (s, 2H), 4.57 (t, J = 6Hz, 1H ), 7.93 (s, 1H) ir (neat) cm -1 ; 3250, 1760, 1455, 1365, 1240, 1200, 1080, 1060, 905, 850 (5) (S) -4- [2- (5-acetoxy-) 2-hydroxy-3,4,6-trimethylphenyl) ethyl] -2,2,4
-Trimethyl-1,3-dioxolane ( 6 ) Raney nickel (W4) 4cm 3 (about 6g) ethanol 20m
Then, a solution of 590 mg of compound 5 in 10 ml of ethanol was added, and the mixture was refluxed for 2 hours. After filtering off the nickel, it is concentrated,
443 mg of crude product were obtained. This was purified by silica gel column chromatography to give the title compound 6 (389 mg, yield 8).
1%).
nmr(CDCl3)δ； 1.32（s,3H）,1.42（s,6H）,1.73（m,2H）， 2.01（s,3H）,2.04（s,3H）,2.09（s,3H）， 2.31（s,3H）,2.67（m,2H）,3.77（s,2H）， 6.16（s,1H） ir（neat）cm-3； 3460,1750,1450,1365,1200,1105, 1050,1005,900,855,810 （６）（Ｓ）−６−ヒドロキシ−2,5,7,8−テトラメチ
ルクロマン−２−メタノール(7) 水素化リチウムアルミニウム147mg（3.87mmol）をテ
トラヒドロフラン10ml中に懸濁させ、化合物6 336mg
（1.00mmol）のテトラヒドロフラン14ml溶液を滴下し
た。還流下で２時間反応させた後、少量の水を加えた。
1N-NaOH水溶液にあけ、有機相と水相に分け、水相をエ
ーテル抽出した。有機相を合わせ亜ニチオン酸ナトリウ
ム水溶液と振った後、乾燥（Na2SO4）、濃縮し、粗生成
物291mgを得た。nmr (CDCl 3 ) δ; 1.32 (s, 3H), 1.42 (s, 6H), 1.73 (m, 2H), 2.01 (s, 3H), 2.04 (s, 3H), 2.09 (s, 3H), 2.31 (S, 3H), 2.67 (m, 2H), 3.77 (s, 2H), 6.16 (s, 1H) ir (neat) cm- 3 ; 3460, 1750, 1450, 1365, 1200, 1105, 1050, 1005, 900,855,810 (6) (S) -6-hydroxy-2,5,7,8-tetramethylchroman-2-methanol ( 7 ) 147 mg (3.87 mmol) of lithium aluminum hydride was suspended in 10 ml of tetrahydrofuran, and 336 mg of compound 6 was suspended.
A solution of (1.00 mmol) in 14 ml of tetrahydrofuran was added dropwise. After reacting for 2 hours under reflux, a small amount of water was added.
The mixture was poured into a 1N-NaOH aqueous solution, separated into an organic phase and an aqueous phase, and the aqueous phase was extracted with ether. The organic phases were combined, shaken with an aqueous solution of sodium dithionite, dried (Na 2 SO 4 ) and concentrated to obtain 291 mg of a crude product.
これをメタノール10mlに溶解させ、塩化第一スズ1gの
1N-塩酸2ml溶液を加え、２時間還流させた。反応液を水
にあけエーテル抽出した後、洗浄（飽和NaHCO3水溶
液）、乾燥（MgSO4）、濃縮し、粗生成物234gを得た。
これをシリカゲルカラムクロマトグラフィーにより精製
し、標題化合物7 189mg（収率80％）を得た。This was dissolved in 10 ml of methanol, and 1 g of stannous chloride was dissolved.
A 2 ml solution of 1N hydrochloric acid was added, and the mixture was refluxed for 2 hours. The reaction solution was poured into water, extracted with ether, washed (saturated NaHCO 3 aqueous solution), dried (MgSO 4 ) and concentrated to obtain 234 g of a crude product.
This was purified by silica gel column chromatography to obtain the title compound 7 (189 mg, yield 80%).
以下の物性値と文献値1)との一致により構造を確認し
た。The structure was confirmed by agreement between the following physical property values and literature values1 ) .
nmr(CCl4-CDCl3)δ； 1.14（s,3H）,1.3（brs,1H）,1.68（t,J＝ 7Hz,2H）,2.02（s,9H）,2.53（t,J＝7Hz, 2H）,3.45（s,2H）,4（brs,1H） m.p.;129.5〜131.0℃ ▲〔α〕21 D▼＝−2.87°（Ｃ＝1.4,CH2Cl2） 文献値m.p.;127〜128℃ 〔α〕D＝−2.88℃（Ｃ＝0.52,CH2Cl2） １）文献:Helv.Chim.Acta.,62, 2384（1979）nmr (CCl 4 -CDCl 3 ) δ; 1.14 (s, 3H), 1.3 (brs, 1H), 1.68 (t, J = 7 Hz, 2H), 2.02 (s, 9H), 2.53 (t, J = 7 Hz, 2H), 3.45 (s, 2H), 4 (brs, 1H) mp; 129.5 to 131.0 ° C ▲ [α] 21 D ▼ = -2.87 ° (C = 1.4, CH 2 Cl 2 ) Literature mp; 127 to 128 ° C. [α] D = -2.88 ℃ (C = 0.52 , CH 2 Cl 2) 1) Document:. Helv.Chim.Acta, 62, 2384 ( 1979)
Claims (2)
環化することを特徴とする一般式 で表されるクロマン誘導体の製造方法。(1) General formula (Wherein X represents a protecting group for a hydroxyl group) after reductively desulfurizing and deprotecting a compound represented by the formula:
General formula characterized by cyclization A method for producing a chroman derivative represented by the formula:
マトロピー転位反応を行い、 一般式 （式中、Ｘは水酸基の保護基を示す） で表される化合物を得、次いで該化合物を、還元的に脱
硫し、脱保護した後、環化することを特徴とする一般式 で表されるクロマン誘導体の製造方法。(2) Is represented by the general formula (In the formula, X represents a protecting group for a hydroxyl group) and a 2,3-digmatropic rearrangement reaction with a trimethylhydroquinone derivative represented by the general formula: Wherein X represents a protecting group for a hydroxyl group, and the compound is reductively desulfurized, deprotected, and then cyclized. A method for producing a chroman derivative represented by the formula:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62225863A JP2620251B2 (en) | 1987-09-09 | 1987-09-09 | Method for producing chroman derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62225863A JP2620251B2 (en) | 1987-09-09 | 1987-09-09 | Method for producing chroman derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6468366A JPS6468366A (en) | 1989-03-14 |
| JP2620251B2 true JP2620251B2 (en) | 1997-06-11 |
Family
ID=16836028
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62225863A Expired - Lifetime JP2620251B2 (en) | 1987-09-09 | 1987-09-09 | Method for producing chroman derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2620251B2 (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6949684B2 (en) | 1998-03-03 | 2005-09-27 | Daiso Co., Ltd. | Process for preparing 1,2,4-butanetriol |
| CA2322480A1 (en) * | 1998-03-03 | 1999-09-10 | Daiso Co., Ltd. | Process for producing 1,2,4-butanetriol |
| JP4845776B2 (en) * | 2007-03-07 | 2011-12-28 | 株式会社不二鉄工所 | Web cutting and winding method |
-
1987
- 1987-09-09 JP JP62225863A patent/JP2620251B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6468366A (en) | 1989-03-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4248889A (en) | 3,5-Dihydroxypentanoic ester derivatives having antihyperlipaemic activity | |
| HUE025904T2 (en) | Methods for purifying trans-(-)-delta9-tetrahydrocannabinol and trans-(+)-delta9-tetrahydrocannabinol | |
| EP1840125B1 (en) | Intermediates for the preparation of dioxane-2-alkyl carbamates | |
| WO1994008943A1 (en) | 2-amino-1,3-propanediol compound and immunosuppressant | |
| Effenberger et al. | Stereoselective synthesis of biologically active tetronic acids | |
| FR2565232A1 (en) | NOVEL FATTY ACID DIESTERS AND A, A-TREHALOSE, PROCESS FOR THEIR PREPARATION AND THERAPEUTIC USE THEREOF | |
| CA2099444C (en) | Process for preparing tert-butyl (3r,5s)-6-hydroxy-3,5-o- isopropylidene-3,5-dihydroxyhexanoate | |
| US4113873A (en) | 8-azaprostanoic acid derivatives | |
| JP2620251B2 (en) | Method for producing chroman derivative | |
| JPS63310882A (en) | Polyoxygenated labdane derivative and manufacture | |
| US4343796A (en) | 2,3-Bis-hydroxybenzyl-derivatives | |
| Forzato et al. | Baker's yeast reduction of 4-hetero-2-(2-nitroethyl) cyclohexanones | |
| FR2486076A1 (en) | AMINOCYCLOPENTANONE AMIDES, THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM | |
| US4024181A (en) | Analogues of prostanoic acids | |
| EP0685473B1 (en) | Benzoheterocyclic compounds, as antioxidants | |
| PT87927B (en) | 7- (1H-PYRROL-3-YLO) ACIDS, OF ITS CORRESPONDING DELTA-LACTONES AND SALTS, AND OF PHARMACEUTICAL COMPOSITIONS THAT CONTAIN THEM | |
| Cantrell | Reactivity of photochemically excited 3-acylthiophenes, 3-acylfurans, and the formylthiophenes and furans | |
| EP0003221B1 (en) | Process for the manufacture of 3,4-dihydro-benzopyran derivatives and starting materials in this process | |
| US5902886A (en) | Method for synthesizing oxetan-2-ones and intermediates for their preparation | |
| EP0217135B1 (en) | Spiro[benzofuran-2(3H), 1'cycloheptane]s, a process and intermediates for their preparation and their use as medicaments | |
| JP2517743B2 (en) | Production method of optically active alcohol | |
| US4296121A (en) | Novel prostaglandin derivatives of the Δ2-PGF2 and Δ2-PGE2 series and process for their manufacture | |
| FR2488604A1 (en) | HETEROPROSTAGLANDIN DERIVATIVES AND METHODS OF PREPARATION THEREOF | |
| JP4690039B2 (en) | Taxane derivative functionalized at position 14 and process for its production | |
| Chikashita et al. | Stereoselective Synthesis of Trans Isomers of a Volatile Compound Isolated from the Elm Bark Beetle" Pteleobius vittatus" via Stereospecific Cyclodehydration Route. |