JPH0570387A - Method for producing (s)-(-)-dihydro-alpha-damascol - Google Patents
Method for producing (s)-(-)-dihydro-alpha-damascolInfo
- Publication number
- JPH0570387A JPH0570387A JP3262517A JP26251791A JPH0570387A JP H0570387 A JPH0570387 A JP H0570387A JP 3262517 A JP3262517 A JP 3262517A JP 26251791 A JP26251791 A JP 26251791A JP H0570387 A JPH0570387 A JP H0570387A
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- compound
- trimethyl
- reaction
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は、フル−ツ様あるいはフ
ラワ−様の香気香味を有し、食品用あるいは香粧品用の
調合香料の素材として有用な（ｓ）−（−）−α−ダマ
スコンの合成中間体である（ｓ）−（−）−デヒドロ−
α−ダマスコールの新規な製法に関する。BACKGROUND OF THE INVENTION The present invention has a flavor-like or flower-like aroma and is useful as a raw material of a compounded flavor for foods or cosmetics (s)-(-)-α-. (S)-(-)-dehydro- which is a synthetic intermediate of Damascon
The present invention relates to a new method for producing α-Damascor.
【０００２】[0002]
【従来の技術】本発明者らは先に後記式（１）で表され
る（ｓ）−（−）−α−ダマスコンのの新規な製造方法
として下記反応式（Ａ）に従う製法を提案した（特願平
３−６２４７５号）。2. Description of the Related Art The inventors of the present invention have previously proposed a process according to the following reaction formula (A) as a novel process for producing (s)-(-)-α-damascon represented by the following formula (1). (Japanese Patent Application No. 3-62475).
【０００３】[0003]
【化４】 [Chemical 4]
【０００４】式中、Ｂｕはブチル基を表し、ＤＭＳＯは
ジメチルスルホキサイドを表す。In the formula, Bu represents a butyl group and DMSO represents dimethyl sulfoxide.
【０００５】[0005]
【発明が解決しようとする課題】しかしながら、上記反
応式（Ａ）によれば、式（５）の化合物から式（８）の
化合物を合成する際に人体に有害とされている錫化合物
を使用していること及び式（５）の化合物から式（３）
の化合物に至るまで４工程を要し、さらに収率の点にお
いても改善を必要とするという課題がある。However, according to the above reaction formula (A), a tin compound which is harmful to the human body is used when the compound of formula (8) is synthesized from the compound of formula (5). From the compound of formula (5)
There is a problem that 4 steps are required to reach the compound of (1) and further improvement is required in terms of yield.
【０００６】[0006]
【課題を解決するための手段】本発明者らは反応工程の
短縮及び錫化合物を使用しない反応方法につき鋭意研究
した。その結果、式（５）の化合物をテトラ−ｎ−ブチ
ルアンモニウムハライド及び１−ハロゲノ−２−ブチン
とを塩基の存在下に反応させることにより後記式（４）
の化合物を容易に合成することができ、さらこの式
（４）の化合物をテトラメチルエチレンジアミン（以
下、ＴＭＥＤＡと称する）及びｎ−ブチルリチウム（ｎ
-ＢuＬi）の存在下にＷｉｔｔｉｇ転位反応させること
により式（３）化合物が一挙に得られることを見いだし
本発明を完成した。[Means for Solving the Problems] The inventors of the present invention have earnestly studied the shortening of the reaction process and the reaction method not using a tin compound. As a result, by reacting the compound of formula (5) with tetra-n-butylammonium halide and 1-halogeno-2-butyne in the presence of a base, the following formula (4)
The compound of formula (4) can be easily synthesized, and the compound of formula (4) is further added to tetramethylethylenediamine (hereinafter referred to as TMEDA) and n-butyllithium (n.
The present invention was completed by finding that the compound of formula (3) can be obtained all at once by carrying out the Wittig rearrangement reaction in the presence of -BuLi).
【０００７】本発明による式（５）の化合物から式
（３）の化合物を製造する方法は下記に示す反応式
（Ｂ）で表すことができる。The method for producing the compound of formula (3) from the compound of formula (5) according to the present invention can be represented by the following reaction formula (B).
【０００８】[0008]
【化５】 [Chemical 5]
【０００９】式中、Ｘはハロゲン元素を表す。In the formula, X represents a halogen element.
【００１０】この反応で使用される式（５）の化合物
は、同一出願人による発明の名称「光学活性２，４，４
−トリメチル−２−シクロヘキセン−１−オール及びそ
の製法」（特願平３−６２３９３号）の明細書に記載さ
れた方法により容易に合成することができる。その概要
は、例えば下記の反応式Ｃによって示すことができる。The compound of formula (5) used in this reaction is the same as that of the invention of the same applicant as "optical activity 2,4,4".
-Trimethyl-2-cyclohexen-1-ol and a method for producing the same "(Japanese Patent Application No. 3-62393). The outline can be shown, for example, by the following reaction formula C.
【００１１】[0011]
【化６】 [Chemical 6]
【００１２】式中、Ａc2Ｏは無水酢酸を、ＤＭＡＰはジ
メチルアミノピリジンを夫々示す。すなわち、エチルビ
ニルケトンとイソブチルアルデヒドから式（ａ）で表さ
れる２，４，４−トリメチル−２−シクロヘキセン−１
−オンを合成し、これを還元して式（ｂ）で表されるラ
セミ体の２，４，４−トリメチル−２−シクロヘキセン
−１−オールに導き、該ラセミ体アルコールを、従来既
知の酢酸エステル化反応を採用することにより、式
（ｃ）で表される（±）−２，４，４−トリメチル−２
−シクロヘキセニルアセテートに容易に導くことができ
る。In the formula, Ac 2 O represents acetic anhydride, and DMAP represents dimethylaminopyridine. That is, 2,4,4-trimethyl-2-cyclohexene-1 represented by the formula (a) is obtained from ethyl vinyl ketone and isobutyraldehyde.
-One was synthesized and reduced to lead to a racemic 2,4,4-trimethyl-2-cyclohexen-1-ol represented by the formula (b), and the racemic alcohol was converted to a conventionally known acetic acid. By adopting the esterification reaction, (±) -2,4,4-trimethyl-2 represented by the formula (c) is represented.
-Can be easily led to cyclohexenyl acetate.
【００１３】このようにして得られた、ラセミ体のアセ
テートを、例えばブタ肝臓エステラーゼ、ブタすい臓リ
パーゼ等のエステル分解酵素を用いて不斉加水分解し、
更にシリカゲルクロマトグフィー等によって精製するこ
とにより、本発明の出発原料である１００％ｅ.ｅ.（ｅ
ｎａｎｔｈｉｏ ｅｘｃｅｓｓ：光学収率）の（Ｒ）−
（＋）−２，４，４−トリメチル−シクロヘキセン−１
−オール［式（５）の化合物］を容易に得ることができ
る。The racemic acetate thus obtained is asymmetrically hydrolyzed using an esterase such as pig liver esterase or pig pancreatic lipase.
Further purification by silica gel chromatography etc. yields 100% ee (e
(R) -of the nanoexcess: optical yield)
(+)-2,4,4-Trimethyl-cyclohexene-1
-All [compound of formula (5)] can be easily obtained.
【００１４】以下、前記反応式（Ｂ）に従う本発明によ
る式（３）化合物の製造方法を順次詳細に説明する。Hereinafter, a method for producing the compound of formula (3) according to the present invention according to the reaction formula (B) will be sequentially described in detail.
【００１５】まず上記式（４）の化合物は、上記式
（５）の化合物をテトラ−ｎ−ブチルアンモニウムハラ
イド及び塩基の存在下に１−ハロゲノ−２−ブチンと反
応させることにより容易に且つ高収率で得ることができ
る。First, the compound of the above formula (4) is easily and highly reacted by reacting the compound of the above formula (5) with 1-halogeno-2-butyne in the presence of a tetra-n-butylammonium halide and a base. It can be obtained in yield.
【００１６】この反応に使用することのできる１−ハロ
ゲノ−２−ブチンとしては、例えば１−ブロモ−２ブチ
ン、１−クロロ−２−ブチン、１−フルオロ−２−ブチ
ン及び１−ヨード−２−ブチン等を挙げることができ
る。Examples of the 1-halogeno-2-butyne that can be used in this reaction include 1-bromo-2butyne, 1-chloro-2-butyne, 1-fluoro-2-butyne and 1-iodo-2. -Butyne and the like can be mentioned.
【００１７】またテトラ−ｎ−ブチルアンモニウムハラ
イドとしては、例えばヨウ化テトラ−ｎ−ブチルアンモ
ニウム、塩化−ｎ−ブチルアンモニウム、臭化−ｎ−ブ
チルアンモニウム及びフッ化−ｎ−ブチルアンモニウム
等を挙げることができる。Examples of tetra-n-butylammonium halides include tetra-n-butylammonium iodide, -n-butylammonium chloride, -n-butylammonium bromide and -n-butylammonium fluoride. You can
【００１８】さらに塩基としては、例えば水酸化ナトリ
ウム、水酸化カリウム、水素化ナトリウム、水素化カリ
ウム、ｎ−ブチルリチウム等を挙げることができる。Further, examples of the base include sodium hydroxide, potassium hydroxide, sodium hydride, potassium hydride, n-butyllithium and the like.
【００１９】式（５）の化合物から式（４）の化合物を
合成する際の反応は、例えば式（５）のアルコール１モ
ルに対してテトラ−ｎ−ブチルアンモニウムハライド約
０．００５〜約０．５モル［約０．００５〜約０．５当
量（以下、ｅｑと表す）］、塩基性物質約１〜約５０モ
ル（約１〜約５０ｅｑ）及び式（５）の化合物に対して
約０．１〜約５重量倍の水を加え、この混合物を撹拌し
ながら１−ハロゲノ−２−ブチン約１〜約１０モル（約
１〜約１０ｅｑ）を約１〜約３０分間で滴下し、その後
約０〜約８０℃にて約１〜約２４時間撹拌することによ
り行なうことができる。反応終了後反応混合物を水中に
注入しエーテルで抽出する。エーテル層を飽和塩化アン
モニウム、飽和食塩水などで洗浄し、硫酸マグネシウム
などの乾燥剤で脱水乾燥後、溶媒を除去して粗製物を得
る。得られる粗製物を例えばシリカゲルクロマトグラフ
ィー（例えばｎ−ヘキサン：酢酸エチル＝２９：１）に
て精製し、目的の化合物（４）を得る。The reaction for synthesizing the compound of formula (4) from the compound of formula (5) is carried out, for example, by adding about 0.005 to about 0 tetra-n-butylammonium halide to 1 mol of the alcohol of formula (5). 0.5 mol [about 0.005 to about 0.5 equivalent (hereinafter referred to as eq)], about 1 to about 50 mol of a basic substance (about 1 to about 50 eq) and about 5 to the compound of the formula (5). 0.1 to about 5 times by weight of water is added, and about 1 to about 10 moles of 1-halogeno-2-butyne (about 1 to about 10 eq) is added dropwise over about 1 to about 30 minutes while stirring the mixture. Thereafter, the stirring can be performed at about 0 to about 80 ° C. for about 1 to about 24 hours. After completion of the reaction, the reaction mixture is poured into water and extracted with ether. The ether layer is washed with saturated ammonium chloride, saturated saline and the like, dried and dried with a drying agent such as magnesium sulfate, and then the solvent is removed to obtain a crude product. The obtained crude product is purified by, for example, silica gel chromatography (for example, n-hexane: ethyl acetate = 29: 1) to obtain the target compound (4).
【００２０】次に式（４）の化合物から式（３）の化合
物を合成するには、式（４）のエーテル化合物１モルに
対してＴＭＥＤＡ約０．１〜約５モル（約０．１〜約５
ｅｑ）及び式（４）の化合物に対して約３〜約３０重量
倍の乾燥エーテル等の有機溶媒を加え混合する。この混
合物を撹拌しながらドライアイス−アセトン−液体窒素
等の冷媒を用いて約−８５〜約−５０℃に冷却する。そ
こへ例えばｎ−ヘキサン、エーテル等の有機溶媒に約１
〜約２規定程度の濃度に溶解したｎ−ブチルリチウム約
１〜約５モル（約１〜約５ｅｑ）を約−８５〜約−５０
℃程度に保ちながら約１０〜約１２０分間で滴下する。
この混合物を同温度に冷却しながら更に約０．５〜約５
時間撹拌する。その後約−４０〜約−１０℃まで昇温し
同温度で約０．５〜約５時間撹拌して反応を終了する。
反応混合物を飽和塩化アンモニウム、飽和食塩水などに
注入し、エーテル等で数回抽出する。溶媒層を脱水乾燥
後、溶媒を除去して化合物（３）の粗製物を得る。この
粗製物をシリカゲルクロマトグラフィー等で精製するこ
とにより目的とする式（３）の化合物を高純度で得るこ
とができる。該式（３）の化合物は、前記反応式Ａに従
って側鎖の還元及び水酸基の酸化反応を行うことにより
容易に式（３）で表される（ｓ）−（−）−α−ダマス
コンに導くことができる。Next, in order to synthesize the compound of formula (3) from the compound of formula (4), about 0.1 to about 5 mol (about 0.1 mol) of TMEDA is added to 1 mol of the ether compound of formula (4). ~ About 5
eq) and the compound of formula (4) are added in an amount of about 3 to about 30 times by weight an organic solvent such as dry ether and mixed. The mixture is cooled to about −85 to about −50 ° C. with stirring using a refrigerant such as dry ice-acetone-liquid nitrogen. There, for example, an organic solvent such as n-hexane or ether is added to about 1
~ N-butyllithium dissolved in a concentration of about 2N about 1 to about 5 mol (about 1 to about 5eq) about -85 to about -50.
While maintaining the temperature at about 0 ° C, the solution is added dropwise for about 10 to about 120 minutes.
While cooling the mixture to the same temperature, about 0.5 to about 5
Stir for hours. Thereafter, the temperature is raised to about −40 to about −10 ° C., and the reaction is completed by stirring at the same temperature for about 0.5 to about 5 hours.
The reaction mixture is poured into saturated ammonium chloride, saturated saline and the like, and extracted several times with ether and the like. After the solvent layer is dehydrated and dried, the solvent is removed to obtain a crude compound (3). The target compound of formula (3) can be obtained in high purity by purifying this crude product by silica gel chromatography or the like. The compound of formula (3) is easily converted into (s)-(-)-α-damascon represented by formula (3) by reducing the side chain and oxidizing the hydroxyl group according to the reaction formula A. be able to.
【００２１】以下、参考例及び実施例により本発明の数
態様をさらに具体的に説明する。Hereinafter, several aspects of the present invention will be described more specifically with reference to Examples and Examples.
【００２２】[0022]
【参考例１】２，４，４−トリメチル−２−シクロヘキセン−１−オ
ン［反応式Ｃ中の式（ａ）の化合物］の合成 エチルビニルケトン７５．０ｇ（８９２mmol）とイソブ
チルアルデヒド９６．４ｇ（１．３４ mol）の混合物を
５０℃以下に保ち、かき混ぜながら濃硫酸２．２５ｍｌ
を少しづつ加えた。混合液を室温で５時間かき混ぜた
後、Ｄｅａｎ−Ｓｔａｒｋ ｔｒａｐを装着し、還流条
件下に１６時間反応を行った。残渣を減圧蒸留し、ｂ.
ｐ.５４〜５５℃／５Torrの２，４，４−トリメチル−
２−シクロヘキセン−１−オン８６．２ｇを得た。[Reference Example 1] 2,4,4-trimethyl-2-cyclohexene-1-o
Synthesis of the compound of formula (a) in reaction formula C] A mixture of 75.0 g (892 mmol) of ethyl vinyl ketone and 96.4 g (1.34 mol) of isobutyraldehyde was kept at 50 ° C. or lower, and concentrated while stirring. 2.25 ml
Was added little by little. After stirring the mixed solution at room temperature for 5 hours, a Dean-Stark trap was attached, and a reaction was performed for 16 hours under reflux conditions. The residue is distilled under reduced pressure, b.
p.54-55 ° C / 5 Torr 2,4,4-trimethyl-
86.2 g of 2-cyclohexen-1-one was obtained.
【００２３】[0023]
【参考例２】（±）−２，４，４−トリメチル−２−シクロヘキセン
−１−オール［反応式Ｃ中の式（ｂ）の化合物］の合成 エーテル８００ｍｌに水素化リチウムアルミニウム１
８．５ｇ（４８６mmol）を溶解し、この溶液をかき混ぜ
ながら０℃に冷却し、参考例１で得られたケトン体６
７．１ｇ（４８６mmol）をエーテル３００ｍｌに溶解し
た溶液を滴下した。０℃で１時間かき混ぜた後、水を少
しづつ加えて水素化リチウムアルミニウムを分解した。
固形物をろ過し洗浄後、濾液を濃縮して残渣を減圧蒸留
してｂ．ｐ．，８９〜９０℃／１９Torrの（±）−２，
４，４−トリメチル−２−シクロヘキセン−１−オール
６２．８ｇを得た。Reference Example 2 (±) -2,4,4-trimethyl-2-cyclohexene
-1-ol [Compound of formula (b) in reaction formula C] Synthetic ether 800 ml was added with lithium aluminum hydride 1
8.5 g (486 mmol) was dissolved, the solution was cooled to 0 ° C. with stirring, and the ketone body 6 obtained in Reference Example 1 was dissolved.
A solution prepared by dissolving 7.1 g (486 mmol) in 300 ml of ether was added dropwise. After stirring at 0 ° C. for 1 hour, water was added little by little to decompose lithium aluminum hydride.
After filtering and washing the solid, the filtrate is concentrated and the residue is distilled under reduced pressure. B. p. , 89-90 ° C / 19 Torr (±) -2,
62.8 g of 4,4-trimethyl-2-cyclohexen-1-ol was obtained.
【００２４】[0024]
【参考例３】（±）−２，４，４−トリメチル−２−シクロヘキセニ
ルアセテート[反応式Ｃ中の式（ｃ）の化合物］の合成 参考例２で得られたラセミ体アルコール６１．５ｇ（４
３９mmol）、無水酢酸６７．３ｇ（６５９mmol）及びピ
リジン７７ｍｌの混合物をかき混ぜながら０℃に冷却
し、そこへＤＭＡＰ４．３ｇ（３５．２mmol）をすこし
づつ加えた。さらに０℃で１時間かき混ぜた後、反応液
を氷水中に注ぎエーテルで抽出する。抽出物を硫酸銅水
溶液、炭酸ナトリウム水溶液及び食塩水で洗浄し、硫酸
マグネシウムで乾燥した後エーテルを回収し、残渣を減
圧蒸留してｂ．ｐ．８２〜８４℃／１０.５Torrの
（±）−２，４，４−トリメチル−２−シクロヘキセニ
ルアセテート７５．７ｇを得た。Reference Example 3 (±) -2,4,4-trimethyl-2-cyclohexeni
Synthesis of luacetate [compound of formula (c) in reaction formula C] 61.5 g (4%) of racemic alcohol obtained in Reference Example 2
39 mmol), 67.3 g (659 mmol) of acetic anhydride and 77 ml of pyridine were stirred and cooled to 0 ° C., and 4.3 g (35.2 mmol) of DMAP was added thereto little by little. After stirring at 0 ° C. for 1 hour, the reaction solution is poured into ice water and extracted with ether. The extract was washed with an aqueous solution of copper sulfate, an aqueous solution of sodium carbonate and brine, dried over magnesium sulfate and then the ether was recovered, and the residue was distilled under reduced pressure to b. p. 75.7 g of (±) -2,4,4-trimethyl-2-cyclohexenyl acetate having a temperature of 82 to 84 ° C./10.5 Torr was obtained.
【００２５】[0025]
【参考例４】（Ｒ）−（＋）−２，４，４−トリメチル−２−シクロ
ヘキセン−１−オール［式（５）の化合物］の合成 式（ｃ）の化合物２６．３ｇ（１４５mmol）を０．１モ
ル燐酸バッファー（イオン交換水：メタノール＝８：
２；ｐＨ７．５）１．１ｌ中に分散させ、激しくかき混
ぜながら−１０℃に冷却し、ブタ肝臓エステラーゼ（シ
グマ社製）５０２５０unitを加えて６５時間酵素分解を
行った。反応液を食塩と塩化アンモニウムで飽和させ、
エーテルで３回抽出した。抽出液を炭酸ナトリウム、食
塩水で洗浄し、炭酸マグネシウムで乾燥後エーテルを回
収し、残渣２７．５ｇをシリカゲルクロマトグラフィー
により精製した。その結果、式（７）の化合物、（Ｒ）
−（＋）−２，４，４−トリメチル−２−シクロヘキセ
ン−１−オール５．３２ｇを得た。この化合物の物性値
は、ｂ．ｐ．６３〜６４℃／３Torr；［α］D＝＋９
５．７°（２１℃）（Ｃ＝１．１３、ＭｅＯＨ）；１０
０％ｅ.ｅ．であった。Reference Example 4 (R)-(+)-2,4,4-trimethyl-2-cyclo
Synthesis of hexen-1-ol [compound of formula (5)] 26.3 g (145 mmol) of the compound of formula (c) in 0.1 mol phosphate buffer (ion exchanged water: methanol = 8:
2; pH 7.5) was dispersed in 1.1 liter, cooled to -10 ° C with vigorous stirring, and 50250 unit of pig liver esterase (Sigma) was added and enzymatically decomposed for 65 hours. Saturate the reaction solution with sodium chloride and ammonium chloride,
Extract 3 times with ether. The extract was washed with sodium carbonate and brine, dried over magnesium carbonate, ether was recovered, and 27.5 g of the residue was purified by silica gel chromatography. As a result, the compound of formula (7), (R)
5.32 g of-(+)-2,4,4-trimethyl-2-cyclohexen-1-ol was obtained. The physical properties of this compound are as described in b. p. 63 to 64 ° C / 3 Torr; [α] D = + 9
5.7 ° (21 ° C.) (C = 1.13, MeOH); 10
0% ee Met.
【００２６】[0026]
【実施例１】（Ｒ）−（＋）−２，４，４，−トリメチル−２−シク
ロヘキセン−１−イル−２−ブチニルエーテル［式
（４）の化合物］の合成 １０ミリリットルのナスフラスコにＮａＯＨ６４０ｍｇ
（１２ｍｍｏｌ，４．０ｅｑ）、水２３１ｍｇ、ヨウ化
テトラ−ｎ−ブチルアンモニウム７４ｍｇ（０．２ｍｍ
ｏｌ，０．０５ｅｑ）及び式（５）の（Ｒ）−（＋）−
２，４，４−トリメチル−２−シクロヘキセン−１−オ
ール５６０ｍｇ（４．０ｍｍｏｌ）を仕込み、そこへ室
温条件で１−ブロモ−２−ブチン７９７ｍｇ（６．０ｍ
ｍｏｌ，１．５ｅｑ）を５分間で滴下し、室温下約２０
時間撹拌する。反応終了後、反応液を水中に注ぎエーテ
ルで抽出する。エーテル層を飽和塩化アンモニウム水溶
液で洗浄後、硫酸マグネシウムで乾燥し、溶液をエバポ
レーターで濃縮して残渣をシリカゲルクロマトグラフィ
ー（ｎ−ヘキサン：酢酸エチル＝２９：１）で精製して
式（４）のエーテル体精製物７４７ｍｇ（収率９７％）
を得た。この化合物の物性値は［α］D＝＋２１．２°
（２１℃；Ｃ＝３．０３，ＥｔＯＨ）。Example 1 (R)-(+)-2,4,4, -trimethyl-2-cyclo
Rohexen-1-yl-2-butynyl ether [Formula
Compound of (4)] NaOH 640 mg in a 10 ml eggplant flask.
(12 mmol, 4.0 eq), water 231 mg, tetra-n-butylammonium iodide 74 mg (0.2 mm
ol, 0.05 eq) and (R)-(+)-of the formula (5).
2,4,4-Trimethyl-2-cyclohexen-1-ol (560 mg, 4.0 mmol) was charged, and 1-bromo-2-butyne (797 mg, 6.0 m) was added thereto at room temperature.
mol, 1.5 eq) was added dropwise over 5 minutes, and at room temperature about 20
Stir for hours. After completion of the reaction, the reaction solution is poured into water and extracted with ether. The ether layer was washed with a saturated aqueous solution of ammonium chloride, dried over magnesium sulfate, the solution was concentrated with an evaporator, and the residue was purified by silica gel chromatography (n-hexane: ethyl acetate = 29: 1) to obtain the compound of formula (4). Purified ether product 747 mg (yield 97%)
Got The physical properties of this compound are [α] D = + 21.2 °
(21 ° C; C = 3.03, EtOH).
【００２７】[0027]
【実施例２】（Ｓ）−（−）−デヒドロ−α−ダマスコール［式
（３）の化合物］の合成 実施例１で得られた式（４）のエーテル体３４６ｍｇ、
乾燥エーテル２．０ｍｌ、テトラメチルエチレンジアミ
ン（ＴＭＥＤＡ）２７０μｌ（１．８ｍｍｏｌ，１．０
ｅｑ）を仕込み、この溶液をアセトン−ドライアイス−
液体窒素浴で−８５℃に冷却する。そこへｎ−ＢｕＬｉ
−ヘキサン溶液（１．６Ｎ）３．４ｍｌ（５．４ｍｍｏ
ｌ，３．０ｅｑ）を−８５〜−８０℃に保ちながら３５
分間で滴下し、同温で２時間かき混ぜた後昇温し、−４
０〜−３０℃で１．５時間撹拌する。反応液を塩化アン
モニウム水溶液中に注ぎ、エーテルで抽出する。抽出液
を洗浄後、乾燥して濃縮し、残渣をシリカゲルクロマト
グラフィーにより精製し、式（３）の（Ｓ）−（−）−
デヒドロ−α−ダマスコール１８８ｍｇを得た（Ｙ＝５
４％）。その物性値は次のとおりであった。［α］D＝
−２０８°（２１℃；Ｃ＝２．７５，ＥｔＯＨ）。Example 2 (S)-(−)-dehydro-α-damascol [formula
Compound of (3)] 346 mg of ether of formula (4) obtained in Example 1
2.0 ml of dry ether, 270 μl of tetramethylethylenediamine (TMEDA) (1.8 mmol, 1.0)
eq) and charged with acetone-dry ice-
Cool to -85 ° C with a liquid nitrogen bath. N-BuLi there
-Hexane solution (1.6 N) 3.4 ml (5.4 mmo
1, 3.0 eq) while maintaining at −85 to −80 ° C.
Dropwise over a period of 2 minutes, stir at the same temperature for 2 hours, and then raise the temperature, -4
Stir at 0--30 ° C for 1.5 hours. The reaction solution is poured into an aqueous solution of ammonium chloride and extracted with ether. The extract is washed, dried and concentrated, and the residue is purified by silica gel chromatography to give (S)-(-)-of formula (3).
188 mg of dehydro-α-damaskol was obtained (Y = 5
4%). The physical properties were as follows. [Α] D =
-208 ° (21 ° C; C = 2.75, EtOH).
【００２８】[0028]
【発明の効果】本発明によれば、高光学純度を有する
（Ｒ）−（＋）−２，４，４−トリメチル−２−シクロ
ヘキセン−１−オールを出発原料とし、短い反応工程に
より香料物質として有用な（Ｓ）−（−）−α−ダマス
コンの合成中間体である（ｓ）−（−）−デヒドロ−α
−ダマスコールを工業的に極めて有利に、且つ高光学純
度をもって製造することができる。INDUSTRIAL APPLICABILITY According to the present invention, (R)-(+)-2,4,4-trimethyl-2-cyclohexen-1-ol having a high optical purity is used as a starting material, and a fragrance substance is produced by a short reaction process. (S)-(−)-dehydro-α which is a synthetic intermediate of (S)-(−)-α-damascon useful as
-Damascor can be produced industrially with great advantage and with high optical purity.
───────────────────────────────────────────────────── フロントページの続き (72)発明者 天池 正康 神奈川県川崎市中原区苅宿335 長谷川香 料株式会社川崎研究所内 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Masayasu Amaike 335 Kayajuku, Nakahara-ku, Kawasaki-shi, Kanagawa Hasegawa Kaori Co., Ltd.
Claims (1)
２−シクロヘキセン−１−オ−ルをテトラ−ｎ−ブチル
アンモニウムハライド及び塩基の存在下に１−ハロゲノ
−２−ブチンと反応させて、下記式（４） 【化２】 で示される（Ｒ）−（＋）−２，４，４−トリメチル−
２−シクロヘキセニル−２−ブチニルエーテルを形成さ
せ、該式（４）の化合物をテトラメチルエチレンジアミ
ン（ＴＭＥＤＡ）及びｎ−ブチルリチウムの存在下にウ
ィッティヒ（Ｗｉｔｔｉｇ）転位反応を行うことを特徴
とする下記式（３） 【化３】 で示される（ｓ）−（−）−デヒドロ−α−ダマスコー
ルの製造方法。1. The following formula (5): (R)-(+)-2,4,4-trimethyl-
2-Cyclohexene-1-ol was reacted with 1-halogeno-2-butyne in the presence of tetra-n-butylammonium halide and a base to give the following formula (4): (R)-(+)-2,4,4-trimethyl-
2-cyclohexenyl-2-butynyl ether is formed, and the compound of the formula (4) is subjected to a Wittig rearrangement reaction in the presence of tetramethylethylenediamine (TMEDA) and n-butyllithium. Formula (3) below The manufacturing method of (s)-(-)-dehydro- (alpha) -damaskol shown by these.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP26251791A JP2804654B2 (en) | 1991-09-17 | 1991-09-17 | Method for producing (S)-(-)-dehydro-α-damaschol |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP26251791A JP2804654B2 (en) | 1991-09-17 | 1991-09-17 | Method for producing (S)-(-)-dehydro-α-damaschol |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH0570387A true JPH0570387A (en) | 1993-03-23 |
| JP2804654B2 JP2804654B2 (en) | 1998-09-30 |
Family
ID=17376907
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP26251791A Expired - Fee Related JP2804654B2 (en) | 1991-09-17 | 1991-09-17 | Method for producing (S)-(-)-dehydro-α-damaschol |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2804654B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009537132A (en) * | 2006-05-18 | 2009-10-29 | レール・リキード−ソシエテ・アノニム・プール・レテュード・エ・レクスプロワタシオン・デ・プロセデ・ジョルジュ・クロード | Use of mixtures of solid carbonic acid and liquid nitrogen in quick freezing applications |
-
1991
- 1991-09-17 JP JP26251791A patent/JP2804654B2/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009537132A (en) * | 2006-05-18 | 2009-10-29 | レール・リキード−ソシエテ・アノニム・プール・レテュード・エ・レクスプロワタシオン・デ・プロセデ・ジョルジュ・クロード | Use of mixtures of solid carbonic acid and liquid nitrogen in quick freezing applications |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2804654B2 (en) | 1998-09-30 |
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