JPH0631249B2 - Method for producing thiophane derivative - Google Patents
Method for producing thiophane derivativeInfo
- Publication number
- JPH0631249B2 JPH0631249B2 JP28003784A JP28003784A JPH0631249B2 JP H0631249 B2 JPH0631249 B2 JP H0631249B2 JP 28003784 A JP28003784 A JP 28003784A JP 28003784 A JP28003784 A JP 28003784A JP H0631249 B2 JPH0631249 B2 JP H0631249B2
- Authority
- JP
- Japan
- Prior art keywords
- dibenzyl
- thiophane
- compound
- tetrahydrofuran
- producing
- 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.)
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Description
【発明の詳細な説明】 本発明はチオファン誘導体の製造法に関するものであ
る。更に詳しくは、テトラヒドロフラン中、３級アミン
の存在下、次式(A) で表される３，４−（１′，３′−ジベンジル−２′−
ケトイミダゾリド）−２−ケトチオファン（以下化合物
Ａと略す）に１，４−ジハロゲノマグネシウムブタン、
次いで二酸化炭素を反応させて次式(B) で表される３，４−（１′，３′−ジベンジル−２′−
ケトイミダゾリド）−２−ヒドロキシ−２−（ω−カル
ボキシブチル）チオファン（以下化合物Ｂと略す）を
得、さらに化合物Ｂを脱水して次式(C) で表される３，４−（１′，３′−ジベンジル−２′−
ケトイミダゾリド）−２−（ω−カルボキシブチリデ
ン）チオファン（以下化合物Ｃと略す）を得、さらに化
合物Ｃを還元して次式(D) で表される３，４−（１′，３′−ジベンジル−２′−
ケトイミダゾリド）−２−（ω−カルボキシブチル）チ
オファン（以下化合物Ｄと略す）を得ることを特徴とす
る製造法に関するものである。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing a thiophane derivative. More specifically, in the presence of a tertiary amine in tetrahydrofuran, the following formula (A) 3,4- (1 ', 3'-dibenzyl-2'-
Keto imidazolide) -2-ketothiophane (hereinafter abbreviated as compound A) with 1,4-dihalogenomagnesium butane,
Then react with carbon dioxide to obtain the following formula (B) 3,4- (1 ', 3'-dibenzyl-2'-
Ketoimidazolide) -2-hydroxy-2- (ω-carboxybutyl) thiophane (hereinafter abbreviated as compound B) is obtained, and compound B is dehydrated to obtain the following formula (C). 3,4- (1 ', 3'-dibenzyl-2'-
Ketoimidazolid) -2- (ω-carboxybutylidene) thiophane (hereinafter abbreviated as compound C) is obtained, and compound C is further reduced to give the following formula (D): 3,4- (1 ', 3'-dibenzyl-2'-
The present invention relates to a process for producing a ketoimidazolide) -2- (ω-carboxybutyl) thiophane (hereinafter abbreviated as compound D).
化合物Ｂ、Ｃ、Ｄはビオチン（ビタミンＨ）を製造する
為の重要な中間体である。Compounds B, C and D are important intermediates for producing biotin (vitamin H).
従来化合物Ｂ、Ｃ、Ｄを製造する方法として特公昭４６
−３５８０号公報および薬学雑誌第８８巻、９６４−９
７０頁（１９６８年）に記載の方法が知られている。こ
の方法は化合物Ａの２位にω−カルボキシブチル基を導
入する方法としてすぐれた方法であるが、化合物Ｂを製
造する際の反応で反応に低温（−２０〜−５０℃）を
必要とする事、臭化マグネシウム等ルイス酸の添加を
必要とする事等、工業的に実施するには種々の欠点を有
している。As a method for producing conventional compounds B, C and D, Japanese Patent Publication No.
-3580 Publication and Pharmaceutical Journal Vol. 88, 964-9
The method described on page 70 (1968) is known. This method is an excellent method for introducing a ω-carboxybutyl group into the 2-position of compound A, but requires a low temperature (-20 to -50 ° C) for the reaction in the production of compound B. However, there are various drawbacks in industrial implementation, such as the need to add a Lewis acid such as magnesium bromide.
本発明者らは、これらの欠点を克服するため、種々検討
した結果、反応溶媒にテトラヒドロフランを用いて３級
アミンの存在下に、化合物Ａと１，４−ジハロゲノマグ
ネシウムブタンを反応させ、次いで二酸化炭素を反応さ
せた場合、各工程とも反応温度は比較的高温（５〜−２
０℃）でもよく、かつルイス酸の添加を必要とせず、化
合物Ｂが高収率で生成することを見出し、本発明を完成
するに至った。In order to overcome these drawbacks, the present inventors have made various investigations, and as a result, reacted with compound A and 1,4-dihalogenomagnesium butane in the presence of a tertiary amine using tetrahydrofuran as a reaction solvent, and then, When carbon dioxide is reacted, the reaction temperature in each step is relatively high (5--2
It was found that Compound B can be produced in a high yield without needing to add a Lewis acid, and the present invention has been completed.
本発明を実施するには１，４−ジクロル又はジブロム等
のジハロゲノブタンと金属マグネシウムより調整される
（この時、１，２−ジブロムエタン、ヨウ素等でマグネ
シウムを活性化してもよい。）１，４−ジハロゲノマグ
ネシウムブタンとテトラヒドロフラン溶液にトリエチル
アミン、Ｎ，Ｎ，Ｎ′，Ｎ′−テトラメチルエチレンジ
アミン、トリ−ｎ−プロピルアミン、Ｎ，Ｎ−ジメチル
アニリン等の３級アミンを加え、これに化合物Ａを反応
させ（反応）次いでこの反応溶液中に炭酸ガスを導入
するか又はドライアイスを添加して反応させた（反応
）のち、（反応、とも反応温度は１０〜−５０℃
で実施できる）、常法により、加水分解することによっ
て、化合物Ｂを製造することが出来る。本反応において
化合物Ａに対する各試薬のモル比はジハロゲノブタン1.
0〜5.0（好ましくは1.5〜2.5）、金属マグネシウム2.0
〜10.0（好ましくは3.0〜5.0）、３級アミン0.1〜5.0
（好ましくは1.5〜2.5）が適当である。３級アミンとし
てはたとえばトリエチルアミン、Ｎ，Ｎ，Ｎ′，Ｎ′−
テトラメチルエチレンジアミン、トリ−ｎ−プロピルア
ミン、Ｎ，Ｎ−ジメチルアニリン等があげられるが、特
にＮ，Ｎ，Ｎ′，Ｎ′−テトラメチルエチレンジアミン
の使用が好ましい。こうして得られた化合物Ｂを、酢
酸、硫酸、ｐ−トルエンスルホン酸等の酸性触媒の存在
下、適当な溶媒例えば、ベンゼン、トルエン、１，２−
ジクロルエタン等の溶媒中で加熱、脱水することにより
化合物Ｃを製造することができ、さらにこうして得られ
る化合物Ｃを酸化パラジウム、パラジウム−活性炭、又
はニッケル−ケイソウ土等の触媒を用いて還元すること
により、化合物Ｄを製造することが出来る。こうして得
られた化合物Ｄは通常の脱ベンジル化によってビオチン
とすることが出来る。In order to carry out the present invention, dihalogenobutane such as 1,4-dichloro or dibrom and metal magnesium are prepared (at this time, magnesium may be activated with 1,2-dibromoethane, iodine, etc.) 1,4- Tertiary amines such as triethylamine, N, N, N ', N'-tetramethylethylenediamine, tri-n-propylamine and N, N-dimethylaniline were added to a solution of dihalogenomagnesium butane and tetrahydrofuran, and Compound A was added thereto. After reacting (reaction), carbon dioxide gas is introduced into this reaction solution or dry ice is added to react (reaction), and then (reaction, both reaction temperature is 10 to -50 ° C).
Compound B) can be produced by hydrolysis according to a conventional method. In this reaction, the molar ratio of each reagent to compound A is dihalogenobutane 1.
0-5.0 (preferably 1.5-2.5), metallic magnesium 2.0
~ 10.0 (preferably 3.0 ~ 5.0), tertiary amine 0.1 ~ 5.0
(Preferably 1.5 to 2.5) is suitable. Examples of the tertiary amine include triethylamine, N, N, N ', N'-
Examples thereof include tetramethylethylenediamine, tri-n-propylamine, N, N-dimethylaniline, etc., and N, N, N ', N'-tetramethylethylenediamine is particularly preferably used. The compound B thus obtained is treated with a suitable solvent such as benzene, toluene, 1,2- in the presence of an acidic catalyst such as acetic acid, sulfuric acid or p-toluenesulfonic acid.
Compound C can be produced by heating and dehydrating in a solvent such as dichloroethane, and further reducing Compound C thus obtained by using a catalyst such as palladium oxide, palladium-activated carbon, or nickel-diatomaceous earth. , Compound D can be produced. The compound D thus obtained can be converted to biotin by conventional debenzylation.
以下に実施例を挙げ具体的に説明するが、本発明はこれ
らに限定されるものではない。Examples will be specifically described below, but the present invention is not limited thereto.
（実施例１） マグネシウム2.4ｇ、テトラヒドロフラン２０ｍの懸
濁液に１，２−ジブロムエタン0.9ｇ、テトラヒドロフ
ラン１０ｍからなる溶液を３０〜３５℃で滴下した。
次いでこれに１，４−ジクロルブタン6.1ｇ、テトラヒ
ドロフラン２０ｍからなる溶液を３５〜４０℃で滴下
し（時々冷却しながら）滴下後同温度で３時間攪拌し
た。この反応液にＮ，Ｎ，Ｎ′，Ｎ′−テトラメチルエ
チレンジアミン2.4ｇおよびテトラヒドロフラン５０ｍ
を加えたのち、−１０〜−２０℃に冷却し、これに
（±）−３，４−（１′，３′−ジベンジル−２′−ケ
トイミダゾリド）−２−ケトチオファン8.0ｇ、テトラ
ヒドロフラン５０ｍからなる溶液を−１０〜−２０℃
で滴下した。滴下後同温度で１時間攪拌、次に炭酸ガス
を３０分導入した。この反応液をあらかじめ冷却してお
いた希塩酸中に１０℃以下で注入し、分解した。この反
応液をトルエンで抽出し、水洗浄後、減圧濃縮した。残
渣の油状物に１０％炭酸カリウム１００ｍを加え、溶
解し、一部不溶の油状物は、酢酸エチルで抽出し、除去
した。水層に酢酸エチルを加え、２０％硫酸でpH7.0に
調整し分液した。有機層を水洗浄後減圧濃縮し、（±）
−３，４−（１′，３′−ジベンジル−２′−ケトイミ
ダゾリド）−２−ヒドロキシ−２−（ω−カルボキシブ
チル）チオファン8.29ｇを油状物として得た。原料のケ
トチオファンに対する収率は79.6％であった。Example 1 A solution of 0.9 g of 1,2-dibromoethane and 10 m of tetrahydrofuran was added dropwise to a suspension of 2.4 g of magnesium and 20 m of tetrahydrofuran at 30 to 35 ° C.
Then, a solution of 6.1 g of 1,4-dichlorobutane and 20 m of tetrahydrofuran was added dropwise thereto at 35 to 40 ° C. (while cooling occasionally), and the mixture was stirred at the same temperature for 3 hours. 2.4 g of N, N, N ', N'-tetramethylethylenediamine and 50 m of tetrahydrofuran were added to this reaction liquid.
Then, the mixture was cooled to −10 to −20 ° C., and (±) -3,4- (1 ′, 3′-dibenzyl-2′-ketoimidazolide) -2-ketothiophane (8.0 g) and tetrahydrofuran (50 m) were added. Solution at -10 to -20 ℃
It was dripped at. After dropping, the mixture was stirred at the same temperature for 1 hour, and then carbon dioxide gas was introduced for 30 minutes. The reaction solution was poured into diluted hydrochloric acid which had been cooled in advance at 10 ° C. or lower to decompose. The reaction solution was extracted with toluene, washed with water, and concentrated under reduced pressure. 100 m of 10% potassium carbonate was added to the residual oily substance to dissolve it, and the partially insoluble oily substance was extracted with ethyl acetate and removed. Ethyl acetate was added to the aqueous layer, pH was adjusted to 7.0 with 20% sulfuric acid, and the layers were separated. The organic layer was washed with water and concentrated under reduced pressure, (±)
8.29 g of -3,4- (1 ', 3'-dibenzyl-2'-ketoimidozolid) -2-hydroxy-2- (ω-carboxybutyl) thiophane was obtained as an oil. The yield of ketothiophane as a raw material was 79.6%.
ＩＲcm-1(KBr)3400,1710〜1690 （実施例２） マグネシウム8.6ｇ、テトラヒドロフラン７５ｍの懸
濁液に１，２−ジブロムエタン3.2ｇ、１，４−ジクロ
ルブタン2.5ｇ、テトラヒドロフラン３７ｍからなる
溶液を３０〜３５℃で２５分要して滴下した。次いでこ
れに１，４−ジクロルブタン20.5ｇ、テトラヒドロフラ
ン７５ｍからなる溶液を３０分要して滴下し、（時々
冷却しながら）滴下後、同温度で３時間攪拌した。この
反応液にＮ，Ｎ，Ｎ′，Ｎ′−テトラメチルエチレンジ
アミン9.0ｇおよびテトラヒドロフラン１９０ｍを加
えたのち−４０〜−４５℃に冷却した。これに（±）−
３，４−（１′，３′−ジベンジル−２′−ケトイミダ
ゾリド）−２−ケトチオファン30.0ｇ、テトラヒドロフ
ラン１９０ｍからなる溶液を−４０〜−４５℃で約１
０分を要して滴下し、同温度で１時間攪拌後、炭酸ガス
を３０分導入した。この反応液をあらかじめ冷却してお
いた１０％硫酸４００ｍ中に１５℃以下で注入し、分
解した。（±）−３，４−（１′，３′−ジベンジル−
２′−ケトイミダゾリド）−２−ヒドロキシ−２−（ω
−カルボキシブチル）チオファンを含むこの反応液にト
ルエンを加え、抽出した。有機層に濃硫酸0.8ｇを加
え、６０−７０℃で１時間攪拌した。反応液を水で洗浄
後、減圧濃縮した。残渣に１０％炭酸カリウム４００ｍ
を加え溶解し、一部不溶の油状物は酢酸エチルで抽出
し、除去した。水層に酢酸エチル３００ｍを加え、２
０％硫酸でpH7.3に調整したのち、有機層を分液、水で
洗浄後減圧濃縮した。（＋）−３，４−（１′，３′−
ジベンジル−２′−ケトイミダゾリド）−２−（ω−カ
ルボキシブチリデン）チオファン34.1ｇを白色の結晶と
して得た。原料ケトチオファンに対する収率は91.1％で
あった。IRcm −1 (KBr) 3400, 1710 to 1690 (Example 2) A suspension of magnesium 8.6 g and tetrahydrofuran 75 m was added with a solution of 1,2-dibromoethane 3.2 g, 1,4-dichlorobutane 2.5 g, and tetrahydrofuran 37 m in 30 It was added dropwise at ˜35 ° C. in 25 minutes. Then, a solution of 20.5 g of 1,4-dichlorobutane and 75 m of tetrahydrofuran was added dropwise thereto over 30 minutes, and after dropwise addition (while cooling occasionally), the mixture was stirred at the same temperature for 3 hours. To this reaction solution, 9.0 g of N, N, N ', N'-tetramethylethylenediamine and 190 m of tetrahydrofuran were added, and then cooled to -40 to -45 ° C. (±)-
A solution consisting of 30.0 g of 3,4- (1 ', 3'-dibenzyl-2'-ketoimidozolid) -2-ketothiophane and 190 m of tetrahydrofuran at -40 to -45 ° C was about 1: 1.
The mixture was added dropwise over 0 minutes, and after stirring at the same temperature for 1 hour, carbon dioxide gas was introduced for 30 minutes. This reaction liquid was poured into 400 m of 10% sulfuric acid that had been cooled in advance at 15 ° C or lower to decompose. (±) -3,4- (1 ', 3'-dibenzyl-
2'-Ketomiimidazolide) -2-hydroxy-2- (ω
Toluene was added to this reaction solution containing -carboxybutyl) thiophane and extraction was performed. 0.8 g of concentrated sulfuric acid was added to the organic layer, and the mixture was stirred at 60 to 70 ° C for 1 hour. The reaction solution was washed with water and concentrated under reduced pressure. 400m of 10% potassium carbonate on the residue
Was added and dissolved, and the partially insoluble oily matter was extracted with ethyl acetate and removed. Add 300m of ethyl acetate to the water layer and add 2
After adjusting the pH to 7.3 with 0% sulfuric acid, the organic layer was separated, washed with water and concentrated under reduced pressure. (+)-3,4- (1 ', 3'-
34.1 g of dibenzyl-2'-ketoimidazolide) -2-([omega] -carboxybutylidene) thiophane was obtained as white crystals. The yield based on the raw material ketothiophane was 91.1%.
又、本化合物は酢酸エチル−エーテルより再結晶するこ
とにより、 融点 ８５〜８６℃ ▲〔α〕23 D▼ ＋236.2゜（Ｃ＝1.0，メタノール） の物性を示した。By recrystallizing this compound from ethyl acetate-ether, it showed the following physical properties: melting point 85-86 ° C. [α] 23 D + 236.2 ° (C = 1.0, methanol).
（実施例３） 実施例２のＮ，Ｎ，Ｎ′，Ｎ′−テトラメチルエチレン
ジアミン9.0ｇの代りにトリエチルアミン9.0ｇを用いた
以外は実施例２と同様に反応および後処理を行ない
（＋）−３，４−（１′，３′−ジベンジル−２′−ケ
トイミダゾリド）−２−（ω−カルボキシブチリデン）
チオファン31.6ｇを白色の結晶として得た。原料ケトチ
オファンに対する収率は84.4％であった。(Example 3) The reaction and post-treatment were carried out in the same manner as in Example 2 except that 9.0 g of triethylamine was used instead of 9.0 g of N, N, N ', N'-tetramethylethylenediamine in Example 2 (+). -3,4- (1 ', 3'-dibenzyl-2'-ketoimidazolid) -2- (ω-carboxybutylidene)
31.6 g of thiophane was obtained as white crystals. The yield based on the raw material ketothiophane was 84.4%.
（実施例４） 実施例３で得られた（＋）−３，４−（１′，３′−ジ
ベンジル−２′−ケトイミダゾリド）−２−（ω−カル
ボキシブチリデン）チオファン20ｇをイソプロピルアル
コール１８０ｍ、水２０ｍの溶液に溶解し、酸化パ
ラジウム1.0ｇを用いて水素圧3.0〜5.0kg/cm2、３５〜
４５℃で５時間接触還元した。(Example 4) 20 g of (+)-3,4- (1 ', 3'-dibenzyl-2'-ketoimidazolide) -2- (ω-carboxybutylidene) thiophane obtained in Example 3 was added to 180 m of isopropyl alcohol. , Dissolved in a solution of 20 m of water, and using 1.0 g of palladium oxide, a hydrogen pressure of 3.0 to 5.0 kg / cm 2 , 35 to 35
It was catalytically reduced at 45 ° C. for 5 hours.
反応後反応液を減圧濃縮し、溶媒を留去した。残渣にト
ルエン１８０ｍ、活性炭2.0ｇを加え、触媒を過し
除去した。液を減圧濃縮し、(-)−３，４−（１′，
３′−ジベンジル−２′−ケトイミダゾリド）−２−
（ω−カルボキシブチル）チオファン19.9ｇを油状物と
して得た。収率99.0％ 本化合物は冷蔵庫で一夜放置することにより結晶化し
た。After the reaction, the reaction solution was concentrated under reduced pressure and the solvent was distilled off. Toluene 180m and activated carbon 2.0g were added to the residue, and the catalyst was removed by filtration. The liquid was concentrated under reduced pressure, and (-)-3,4- (1 ',
3'-dibenzyl-2'-keto imidazolide) -2-
19.9 g of (ω-carboxybutyl) thiophane was obtained as an oil. Yield 99.0% This compound was crystallized by leaving it in the refrigerator overnight.
又、本化合物は酢酸エチル−エーテルより再結晶するこ
とにより、融点９１〜９２℃ ▲〔α〕23 D▼ −26.8゜（Ｃ＝1.0，メタノール） の物性を示した。By recrystallizing this compound from ethyl acetate-ether, it showed physical properties with a melting point of 91 to 92 ° C. [α] 23 D -26.8 ° (C = 1.0, methanol).
Claims (6)
下、３，４−（１′，３′−ジベンジル−２′−ケトイ
ミダゾリド）−２−ケトチオファンに１，４−ジハロゲ
ノマグネシウムブタン、次いで二酸化炭素を反応させる
ことを特徴とする３，４−（１′，３′−ジベンジル−
２′−ケトイミダゾリド）−２−ヒドロキシ−２−（ω
−カルボキシブチル）チオファンの製造法。1. In tetrahydrofuran in the presence of a tertiary amine, 3,4- (1 ', 3'-dibenzyl-2'-ketoimidazolid) -2-ketothiophane, 1,4-dihalogenomagnesium butane, and then carbon dioxide. 3,4- (1 ', 3'-dibenzyl-, characterized in that
2'-Ketomiimidazolide) -2-hydroxy-2- (ω
-Method for producing carboxybutyl) thiophane.
メチルエチレンジアミンである特許請求の範囲第１項記
載の製造法。2. The method according to claim 1, wherein the tertiary amine is N, N, N ', N'-tetramethylethylenediamine.
下、３，４−（１′，３′−ジベンジル−２′−ケトイ
ミダゾリド）−２−ケトチオファンに１，４−ジハロゲ
ノマグネシウムブタン、次いで二酸化炭素を反応させ、
３，４−（１′，３′−ジベンジル−２′−ケトイミダ
ゾリド）−２−ヒドロキシ−２−（ω−カルボキシブチ
ル）チオファンを得て、次いでこれを脱水すること特徴
とする３，４−（１′，３′−ジベンジル−２′−ケト
イミダゾリド）−２−（ω−カルボキシブチリデン）チ
オファンの製造法。3. Tetrahydrofuran in the presence of a tertiary amine, 3,4- (1 ', 3'-dibenzyl-2'-ketoimidazolid) -2-ketothiophane, 1,4-dihalogenomagnesium butane and then carbon dioxide. React
3,4- (1 ', 3'-dibenzyl-2'-ketoimidazolide) -2-hydroxy-2- (ω-carboxybutyl) thiophane is obtained, which is then dehydrated. Process for producing 1 ', 3'-dibenzyl-2'-ketoimidazolid) -2- (ω-carboxybutylidene) thiophane.
メチルエチレンジアミンである特許請求の範囲第３項記
載の製造法。4. The method according to claim 3, wherein the tertiary amine is N, N, N ', N'-tetramethylethylenediamine.
下、３，４−（１′，３′−ジベンジル−２′−ケトイ
ミダゾリド）−２−ケトチオファンに１，４−ジハロゲ
ノマグネシウムブタン、次いで二酸化炭素を反応させ
３，４−（１′，３′−ジベンジル−２′−ケトイミダ
ゾリド）−２−ヒドロキシ−２−（ω−カルボキシブチ
ル）チオファンを得、次いでこれを脱水して３，４−
（１′，３′−ジベンジル−２′−ケトイミダゾリド）
−２−（ω−カルボキシブチリデン）チオファンを得、
更にこれを還元することを特徴とする３，４−（１′，
３′−ジベンジル−２′−ケトイミダゾリド）−２−
（ω−カルボキシブチル）チオファンの製造法。5. Tetrahydrofuran in the presence of a tertiary amine, 3,4- (1 ', 3'-dibenzyl-2'-ketoimidazolid) -2-ketothiophane, 1,4-dihalogenomagnesium butane, and then carbon dioxide. To give 3,4- (1 ', 3'-dibenzyl-2'-ketoimidazolid) -2-hydroxy-2- (ω-carboxybutyl) thiophane, which is then dehydrated to give 3,4-
(1 ', 3'-dibenzyl-2'-ketoimidazolide)
-2- (ω-carboxybutylidene) thiophane is obtained,
Furthermore, it is characterized by reducing it. 3,4- (1 ',
3'-dibenzyl-2'-keto imidazolide) -2-
A method for producing (ω-carboxybutyl) thiophane.
メチルエチレンジアミンである特許請求の範囲第５項記
載の製造法。6. The method according to claim 5, wherein the tertiary amine is N, N, N ', N'-tetramethylethylenediamine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP28003784A JPH0631249B2 (en) | 1984-12-24 | 1984-12-24 | Method for producing thiophane derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP28003784A JPH0631249B2 (en) | 1984-12-24 | 1984-12-24 | Method for producing thiophane derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS61151194A JPS61151194A (en) | 1986-07-09 |
| JPH0631249B2 true JPH0631249B2 (en) | 1994-04-27 |
Family
ID=17619413
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP28003784A Expired - Fee Related JPH0631249B2 (en) | 1984-12-24 | 1984-12-24 | Method for producing thiophane derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0631249B2 (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2125820C (en) * | 1993-07-08 | 2006-05-02 | Masahiko Mizuno | Process for producing thiophene derivative |
| DE4411101C2 (en) * | 1994-03-30 | 1996-02-01 | Merck Patent Gmbh | Process for the preparation of a D - (+) - biotin intermediate |
| JPH09227564A (en) | 1995-12-20 | 1997-09-02 | Sumitomo Chem Co Ltd | Production of imidazole derivative |
| CA2193774C (en) * | 1995-12-26 | 2005-02-01 | Norihiko Hirata | Process for producing 1-hydroxythienoimidazole carboxylic acid and thienoimidazole carboxylic acid |
| EP1167373A1 (en) * | 2000-06-22 | 2002-01-02 | E-Sung Chemicals Co., Ltd. | Ferrocenyldiphosphine-ruthenium complexes and a hydrogenation process of exocyclic double bond of d-thiophene to d-thiophane |
-
1984
- 1984-12-24 JP JP28003784A patent/JPH0631249B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JPS61151194A (en) | 1986-07-09 |
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