JPH0127048B2 - - Google Patents
Info
- Publication number
- JPH0127048B2 JPH0127048B2 JP4404282A JP4404282A JPH0127048B2 JP H0127048 B2 JPH0127048 B2 JP H0127048B2 JP 4404282 A JP4404282 A JP 4404282A JP 4404282 A JP4404282 A JP 4404282A JP H0127048 B2 JPH0127048 B2 JP H0127048B2
- Authority
- JP
- Japan
- Prior art keywords
- homoisotwistane
- present
- sulfuric acid
- hydroxymethyltricyclo
- 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
Links
- MCEWXTWROUCMOU-UHFFFAOYSA-N decahydro-1,6-methanonaphthalene Chemical compound C1CC2C3CCCC2CC1C3 MCEWXTWROUCMOU-UHFFFAOYSA-N 0.000 claims description 14
- -1 hydrogen anion Chemical class 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 6
- NJKIJYKRBHGRME-UHFFFAOYSA-N hexahydro-2-hydroxymethyl-4,7-methanoindan Chemical compound C1C2CCC1C1C2CC(CO)C1 NJKIJYKRBHGRME-UHFFFAOYSA-N 0.000 claims description 4
- RSJKGSCJYJTIGS-UHFFFAOYSA-N undecane Chemical compound CCCCCCCCCCC RSJKGSCJYJTIGS-UHFFFAOYSA-N 0.000 claims description 4
- 238000000034 method Methods 0.000 description 12
- 150000001875 compounds Chemical class 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 8
- 239000012043 crude product Substances 0.000 description 6
- QWTDNUCVQCZILF-UHFFFAOYSA-N isopentane Chemical compound CCC(C)C QWTDNUCVQCZILF-UHFFFAOYSA-N 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
- 239000002994 raw material Substances 0.000 description 5
- 229930195733 hydrocarbon Natural products 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000004215 Carbon black (E152) Substances 0.000 description 3
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 3
- AFABGHUZZDYHJO-UHFFFAOYSA-N dimethyl butane Natural products CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 3
- 150000002430 hydrocarbons Chemical class 0.000 description 3
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 238000004817 gas chromatography Methods 0.000 description 2
- UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- HIPPBUJQSIICJN-UHFFFAOYSA-N 3385-61-3 Chemical compound C12CC=CC2C2CC(O)C1C2 HIPPBUJQSIICJN-UHFFFAOYSA-N 0.000 description 1
- HSPRVWPULGKMRC-UHFFFAOYSA-N 57526-50-8 Chemical compound C12CCCC2C2CC(CO)C1C2 HSPRVWPULGKMRC-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- NHTMVDHEPJAVLT-UHFFFAOYSA-N Isooctane Chemical compound CC(C)CC(C)(C)C NHTMVDHEPJAVLT-UHFFFAOYSA-N 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- JVSWJIKNEAIKJW-UHFFFAOYSA-N dimethyl-hexane Natural products CCCCCC(C)C JVSWJIKNEAIKJW-UHFFFAOYSA-N 0.000 description 1
- 208000001848 dysentery Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- GYNNXHKOJHMOHS-UHFFFAOYSA-N methyl-cycloheptane Natural products CC1CCCCCC1 GYNNXHKOJHMOHS-UHFFFAOYSA-N 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- HIFJUMGIHIZEPX-UHFFFAOYSA-N sulfuric acid;sulfur trioxide Chemical compound O=S(=O)=O.OS(O)(=O)=O HIFJUMGIHIZEPX-UHFFFAOYSA-N 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
Description
【発明の詳細な説明】
本発明は次の式（）：
で表わされる４−ホモイソツイスタン（トリシク
ロ〔５，３，１，03,8〕ウンデカン）の製造法に
関する。
４−ホモイソツイスタン（）の誘導体には、
抗ウイルス作用等の有用な生理作用を有するもの
が多く知られている〔K.Aigami等J.Med.Chem.，
19，536（1976）及びPhytochemistry16，41
（1977）〕。従つて、本発明はこれらの化合物の合
成中間体である４−ホモイソツイスタン（）を
合成する有用な方法である。
従来、４−ホモイソツイスタン（）を製造す
る方法としては、次式（）：
で表わされる８−ヒドロキシメチルトリシクロ
〔５，２，１，02,6〕デカンを濃硫酸及び水素アニ
オン源の存在下で異性化と還元を行う方法が知ら
れている（特開昭52−68166号）。この方法は、４
−ホモイソツイスタン（）への変換選択性が高
いという利点はあるが、原料化合物（）が高価
なロジウム触媒を用いて製造しなければならない
という点で工業的方法として必ずしも満足できる
ものではなかつた。
本発明者らは、４−ホモイソツイスタン（）
の工業的製造法について鋭意研究を行つた結果、
本発明を完成した。
本発明方法は、次の反応式によつて示される。
すなわち、本発明は、３又は４−ヒドロキシメ
チルトリシクロ〔５，２，１，02,6〕デカン（）
を濃硫酸及び水素アニオン源の存在下で異性化と
還元を行つて４−ホモイソツイスタン（）を製
造する方法である。
本発明方法の原料化合物（）は工業的に容易
に入手できるものであり、例えば西独ルール・ヒ
エミー（Ruhr Chemie）より「TCDアルコール
Ｍ」（西独特許第934889号）として市販されてい
る。
本発明方法を実施するには、３又は４−ヒドロ
キシメチルトリシクロ〔５，２，１，02,6〕デカ
ン（）を濃硫酸及び水素アニオン源たる炭化水
素と共に撹拌すればよい。
本発明で使用する濃硫酸は、濃度が75〜100％、
特に90〜98％のものが好ましく、75％未満では異
性化が有効に行われず、また100％を超える発煙
硫酸を用いると酸化反応が併発して目的物の収率
が低下する。濃硫酸は原料化合物（）に対して
当量ないし1000倍（重量）、特に10〜100倍の量を
使用するのが好ましい。
水素アニオン源としては各種の脂肪族及び脂環
式炭化水素を使用できるが、あまり沸点の高いも
のは目的化合物（）との分離が困難となるため
好ましくない。好ましい具体例としては、例えば
ｎ−ペンタン、iso−ペンタン、ｎ−ヘキサン、
ｎ−ヘプタン、iso−オクタン、シクロペンタン、
シクロヘキサン、メチルシクロヘキサン等が挙げ
られる。水素アニオン源の使用量は目的物の収率
にあまり大きな影響を及ぼさないが、多い方がよ
い傾向にあり、一般には原料化合物（）に対し
て10〜1000倍（重量）の範囲で使用するのが望ま
しい。
反応温度は−５〜100℃、特に０〜30℃が好ま
しく、反応は数十分ないし数時間で完了する。
反応後、水素アニオン源たる炭化水素の層を分
取し、蒸留等の手段によつて当該炭化水素を除去
すれば粗生成物が得られる。この粗生成物は、キ
ヤピラリーカラムを用いるガスクロ分析の結果、
４−ホモイソツイスタン（）を約47％、式
（）及び（）で表わされるトリシクロウンデ
カン異性体をそれぞれ約14％及び約７％、その他
の花合物を約32％含む混合物であつた。
【式】【式】
本発明の４−ホモイソツイスタン（）は上記
粗生成物を例えば回転バンド蒸留器を用いて分留
すれば高純度のものとして単離することができ
る。
叙上の如く、本発明方法は一見すると前述の特
開昭52−68166号の方法と同一のように見えるが、
本発明方法では、後者の方法では生成されない式
（）及び（）の化合物が副生することから、
両者は全く異つた経路で反応が進行していること
がわかる。そして、前述した如く、本発明方法
は、原料化合物（）の入手が容易な点で当該公
知方法より工業的方法として有利である。
次に実施例を挙げて説明する。
実施例 １
95％濃硫酸1000ｇを撹拌しながら、これに３−
ヒドロキシメチルトリシクロ〔５，２，１，02,6〕
デカン及び４−ヒドロキシメチルトリシクロ
〔５，２，１，02,6〕デカンの混合物100ｇ（0.6モ
ル）のイソペンタン溶液（イソペンタン1000ｇ）
を約２時間かけて滴下する。滴下終了後さらに１
時間撹拌を続ける。この間反応温度を15℃に保
つ。反応終了後1000ｇの氷水の中へ投入し、ｎ−
ヘキサンで２回抽出する。抽出液を飽和食塩水で
２回洗浄した後、無水硫酸マグネシウム上で乾燥
する。過後蒸留により、粗生成物50.4ｇ（収率
56％）を単離した。この粗生成物のキヤピラリー
カラムによるガスクロ分析の結果、４−ホモイソ
ツイスタンの含量は47％であつた。粗生成物を回
転バンド蒸留器（理論段数40段）で分留する事に
より純度95％の４−ホモイソツイスタン18.5ｇ
（沸点107℃／25mmHg）を得た。
このものの各種スペクトルが標品〔本発明者
ら、Chemistry Letters，1185（1973）：J.Org.
Chem.，40，276（1975）〕のそれと同一であるこ
とから、４−ホモイソツイスタンであることが確
認された。 [Detailed Description of the Invention] The present invention is based on the following formula (): The present invention relates to a method for producing 4-homoisotwistane (tricyclo[5,3,1,0 3,8 ]undecane) represented by Derivatives of 4-homoisotwistane () include:
Many substances are known to have useful physiological effects such as antiviral effects [K. Aigami et al. J. Med. Chem.,
19, 536 (1976) and Phytochemistry 16 , 41
(1977)]. Therefore, the present invention is a useful method for synthesizing 4-homoisotwistane (), which is a synthetic intermediate for these compounds. Conventionally, as a method for producing 4-homoisotwistane (), the following formula (): A method is known in which 8-hydroxymethyltricyclo[5,2,1,0 2,6 ]decane, represented by −68166). This method consists of 4
-Although it has the advantage of high conversion selectivity to homoisotwistane (), it is not necessarily satisfactory as an industrial method in that the raw material compound () must be produced using an expensive rhodium catalyst. Ta. The present inventors have proposed that 4-homoisotwistane ()
As a result of intensive research on industrial manufacturing methods,
The invention has been completed. The method of the present invention is shown by the following reaction formula. That is, the present invention provides 3- or 4-hydroxymethyltricyclo[ 5,2,1,02,6 ]decane ()
This is a method for producing 4-homoisotwistane (2) by isomerizing and reducing it in the presence of concentrated sulfuric acid and a hydrogen anion source. The raw material compound () for the method of the present invention is easily available industrially, and is commercially available, for example, from Ruhr Chemie, West Germany, as "TCD Alcohol M" (West German Patent No. 934889). To carry out the process of the present invention, 3- or 4-hydroxymethyltricyclo[5,2,1,0 2,6 ]decane () may be stirred with concentrated sulfuric acid and a hydrocarbon as a source of hydrogen anions. The concentrated sulfuric acid used in the present invention has a concentration of 75 to 100%,
In particular, 90 to 98% is preferable; if it is less than 75%, isomerization will not be carried out effectively, and if fuming sulfuric acid is used in excess of 100%, oxidation reactions will occur together, resulting in a decrease in the yield of the target product. It is preferable to use concentrated sulfuric acid in an amount equivalent to to 1000 times (by weight), particularly 10 to 100 times the amount of the raw material compound (2). Various aliphatic and alicyclic hydrocarbons can be used as the hydrogen anion source, but those with too high a boiling point are not preferred because they will be difficult to separate from the target compound (2). Preferred specific examples include n-pentane, iso-pentane, n-hexane,
n-heptane, iso-octane, cyclopentane,
Examples include cyclohexane and methylcyclohexane. The amount of hydrogen anion source used does not have a great effect on the yield of the target product, but a larger amount tends to be better, and it is generally used in a range of 10 to 1000 times (by weight) relative to the raw material compound (). is desirable. The reaction temperature is preferably -5 to 100°C, particularly 0 to 30°C, and the reaction is completed in several tens of minutes to several hours. After the reaction, the hydrocarbon layer serving as the source of hydrogen anions is separated, and the hydrocarbon is removed by means such as distillation to obtain a crude product. As a result of gas chromatography analysis using a capillary column, this crude product was found to be
It is a mixture containing about 47% of 4-homoisotwistane (), about 14% and about 7% of tricycloundecane isomers represented by formulas () and (), respectively, and about 32% of other compounds. Ta. [Formula] [Formula] 4-Homoisotwistane () of the present invention can be isolated as a highly pure product by fractionating the above-mentioned crude product using, for example, a rotating band distiller. As mentioned above, at first glance, the method of the present invention appears to be the same as the method of Japanese Patent Application Laid-Open No. 52-68166, but
In the method of the present invention, compounds of formulas () and (), which are not produced in the latter method, are produced as by-products.
It can be seen that both reactions proceed in completely different routes. As mentioned above, the method of the present invention is more advantageous as an industrial method than the known method in that the raw material compound () is easily available. Next, an example will be given and explained. Example 1 While stirring 1000 g of 95% concentrated sulfuric acid, add 3-
Hydroxymethyltricyclo[5,2,1,0 2,6 ]
A solution of 100 g (0.6 mol) of a mixture of decane and 4-hydroxymethyltricyclo[5,2,1,0 2,6 ]decane in isopentane (1000 g of isopentane)
drip over about 2 hours. After dripping, add 1 more
Continue stirring for an hour. During this time, keep the reaction temperature at 15°C. After the reaction was completed, the n-
Extract twice with hexane. The extract is washed twice with saturated brine and then dried over anhydrous magnesium sulfate. After distillation, 50.4 g of crude product (yield
56%) were isolated. As a result of gas chromatography analysis of this crude product using a capillary column, the content of 4-homoisotwistane was 47%. 18.5 g of 4-homoisotwistane with a purity of 95% is obtained by fractionating the crude product using a rotating band distiller (40 theoretical plates).
(boiling point 107°C/25mmHg) was obtained. Various spectra of this product are standard [Inventors, Chemistry Letters, 1185 (1973): J.Org.
Chem., 40 , 276 (1975)], it was confirmed that it was 4-homoisotwistane.
Claims (1)
クロ〔５，２，１，02,6〕デカンを濃硫酸及び水
素アニオン源の存在下で異性化と還元を行うこと
を特徴とする式（）： で表わされる４−ホモイソツイスタン（トリシク
ロ〔５，３，１，03,8〕ウンデカン）の製造法。[Claims] 1 Formula (): A formula () characterized in that 3 or 4-hydroxymethyltricyclo[5,2,1,0 2,6 ]decane represented by isomerized and reduced in the presence of concentrated sulfuric acid and a hydrogen anion source: A method for producing 4-homoisotwistane (tricyclo[5,3,1,0 3,8 ]undecane) represented by
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4404282A JPS58162535A (en) | 1982-03-19 | 1982-03-19 | Production of 4-homotwistane |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4404282A JPS58162535A (en) | 1982-03-19 | 1982-03-19 | Production of 4-homotwistane |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS58162535A JPS58162535A (en) | 1983-09-27 |
| JPH0127048B2 true JPH0127048B2 (en) | 1989-05-26 |
Family
ID=12680559
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP4404282A Granted JPS58162535A (en) | 1982-03-19 | 1982-03-19 | Production of 4-homotwistane |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS58162535A (en) |
-
1982
- 1982-03-19 JP JP4404282A patent/JPS58162535A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS58162535A (en) | 1983-09-27 |
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