JP2906062B2 - Method for producing 2-furylcarbinol derivative - Google Patents
Method for producing 2-furylcarbinol derivativeInfo
- Publication number
- JP2906062B2 JP2906062B2 JP21314689A JP21314689A JP2906062B2 JP 2906062 B2 JP2906062 B2 JP 2906062B2 JP 21314689 A JP21314689 A JP 21314689A JP 21314689 A JP21314689 A JP 21314689A JP 2906062 B2 JP2906062 B2 JP 2906062B2
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- Japan
- Prior art keywords
- reaction
- formula
- furylcarbinol
- general formula
- derivative
- Prior art date
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- Expired - Lifetime
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Description
【発明の詳細な説明】 ＜産業上の利用分野＞ 本発明は医農薬の中間体，とりわけプロスタグランデ
ィン中間体として有用な２−フリルカルビノール誘導体
の製造法に関する。The present invention relates to a method for producing a 2-furylcarbinol derivative useful as an intermediate for medicinal and agricultural chemicals, particularly as a prostaglandin intermediate.
＜従来の技術＞ 従来，上記２−フリルカルビノール誘導体の製造法と
して例えば,4−（２−フリル）−４−ヒドロキシ−１−
ブチンとハロゲン化アルキルとを反応させる方法（特開
昭62-29568号公報）が知られている。<Prior Art> Conventionally, as a method for producing the above 2-furylcarbinol derivative, for example, 4- (2-furyl) -4-hydroxy-1-
A method of reacting butyne with an alkyl halide (JP-A-62-29568) is known.
＜発明が解決しようとする課題＞ しかしながら上記の方法ではリチウムアミド，または
ブチルリチウム等発火の危険性が高く取扱が困難な試薬
を使用するため，工業的には必ずしも満足できるものと
は言い難い。<Problems to be Solved by the Invention> However, the above-mentioned method uses a reagent that is difficult to handle due to a high risk of ignition such as lithium amide or butyllithium, and therefore cannot be said to be industrially satisfactory.
本発明の目的はプロスタグランディン等の中間体であ
る２−フリルカルビノール誘導体を工業的にも有利に製
造することである。An object of the present invention is to produce a 2-furylcarbinol derivative which is an intermediate such as prostaglandin in an industrially advantageous manner.
＜課題を解決するための手段＞ 本発明者らはプロスタグランディンの中間体の製造法
を提供すべく種々検討した結果，フルフラール類と容易
に合成可能なアセチレン性ハロゲノエステル類とを反応
させることにより，工業的にも有利に２−フリルカルビ
ノール誘導体が製造できることを見出し本発明に至っ
た。<Means for Solving the Problems> The present inventors have conducted various studies to provide a method for producing an intermediate of prostaglandin, and as a result, have found that furfurals can be reacted with easily synthesized acetylenic halogenoesters. As a result, the present inventors have found that a 2-furylcarbinol derivative can be produced industrially advantageously, thereby leading to the present invention.
すなわち，本発明は一般式〔Ｉ〕 （式中，R1は水素原子または低級アルキル基を表わ
す。） で示されるフルフラール類と，一般式〔II〕 Ｘ−CH2−Ｃ≡ＣCH2 ｎCOOR2 〔II〕 （式中,Xはハロゲン原子を表わし，R2は水素原子または
低級アルギル基を表わす。ｎは２〜４の整数を表わ
す。） で示されるアセチレン性ハロゲノエステル類とを，亜鉛
及び水の存在下に反応させることを特徴とする一般式
〔III〕 （式中，R1，R2及びｎは前記と同じ意味を表わす。） で示される２−フリルカルビノール誘導体の製造法であ
る。That is, the present invention relates to the general formula [I] (In the formula, R 1 represents a hydrogen atom or a lower alkyl group.) And a general formula [II] X—CH 2 —C≡CCH 2 n COOR 2 [II] (where X is Represents a halogen atom, R 2 represents a hydrogen atom or a lower argyl group, and n represents an integer of 2 to 4.) The acetylenic halogenoester represented by the following formula: Characteristic general formula [III] (Wherein, R 1 , R 2 and n have the same meanings as described above.) A method for producing a 2-furylcarbinol derivative represented by the formula:
以下，本発明について詳細に説明する。 Hereinafter, the present invention will be described in detail.
本発明で使用される上記一般式〔Ｉ〕のフルフラール
類としては,4−メチルフルフラール,4−エチルフルフラ
ール,4−ｎ−プロピルフルフラール,4−イソプロピルフ
ルフラール,4−ｎ−ビチルフルフラール,4−イソブチル
フルフラール,4−tert.−ブチルフルフラール等が例示
される。Examples of the furfural of the general formula (I) used in the present invention include 4-methylfurfural, 4-ethylfurfural, 4-n-propylfurfural, 4-isopropylfurfural, 4-n-bitylfurfural, and 4-furfural. Isobutylfurfural, 4-tert.-butylfurfural and the like are exemplified.
これらのフルフラール類〔Ｉ〕は通常，一般式〔II〕
で示されるアセチレン性ハロゲノエステル類に対して１
〜４倍当量，好ましくは１〜２倍当量使用される。These furfural compounds [I] usually have the general formula [II]
1 to the acetylenic halogenoester represented by
It is used up to 4 times equivalent, preferably 1 to 2 times equivalent.
一般式〔II〕で示されるアセチレン性ハロゲノエステ
ル類としては ６−ブロモ−，または６−クロロ−４−
ヘキシン酸メチル,7−ブロモ−，または７−クロロ−５
−ヘプチン酸メチル,8−ブロモ−，または８−クロロ−
６−オクチン酸メチル等が例示される。As the acetylenic halogenoester represented by the general formula [II], 6-bromo- or 6-chloro-4-
Methyl hexate, 7-bromo-, or 7-chloro-5
-Methyl heptate, 8-bromo-, or 8-chloro-
Examples thereof include 6-methyl octinate.
亜鉛としては，通常粉末または微粉末のものが使用さ
れる。As zinc, powder or fine powder is usually used.
亜鉛は通常，一般式〔II〕で示されるアセチレン性ハ
ロゲノエステル類に対して１〜３倍当量，好ましくは１
〜２倍当量使用される。Zinc is usually used in an amount of 1 to 3 equivalents, preferably 1 equivalent, to the acetylenic halogenoester represented by the general formula [II].
Used up to twice equivalent.
水は通常，一般式〔II〕で示されるアセチレン性ハロ
ゲノエステル類に対して１〜50倍重量使用されるが，そ
の使用量は特に制限されるものではない。Water is usually used in an amount of 1 to 50 times the weight of the acetylenic halogenoester represented by the general formula [II], but the amount thereof is not particularly limited.
本発明においては水以外に有機溶媒を共存させてもよ
く，かかる有機溶媒としては,n−ヘキサン等の脂肪族
系，トルエン，キシレン等の芳香族系炭化水素，あるい
はジエチルエーテルもしくはテトラヒドロフラン等のエ
ーテル系溶媒が挙げられる。In the present invention, an organic solvent other than water may be allowed to coexist. Examples of the organic solvent include aliphatic hydrocarbons such as n-hexane, aromatic hydrocarbons such as toluene and xylene, and ethers such as diethyl ether and tetrahydrofuran. System solvents.
これらの有機溶媒は通常，一般式〔II〕で示されるア
セチレン性ハロゲノエステル類に対して0.1〜30倍重量
使用されるが，その使用量は特に制限されない。These organic solvents are usually used in an amount of 0.1 to 30 times the weight of the acetylenic halogenoester represented by the general formula [II], but the amount used is not particularly limited.
本発明において塩化アンモニウムまたは臭化アンモニ
ウム等のハロゲン化アンモニウムを共存させても良く，
その使用量は通常水に対して0.05〜１倍重量，好ましく
は0.1〜１倍重量である。In the present invention, an ammonium halide such as ammonium chloride or ammonium bromide may coexist.
The used amount is usually 0.05 to 1 times by weight, preferably 0.1 to 1 time by weight with respect to water.
また，ハロゲン化アンモニウムに代えて酸を使用する
こともできる。Further, an acid can be used in place of the ammonium halide.
かかる酸としては，塩酸，リン酸等の鉱酸，または酢
酸等の有機酸が使用され，その使用量は特に制限されな
いが，好ましくは一般式〔II〕で示されるアセチレン性
ハロゲノエステル類に対して0.01〜10倍モルである。As such an acid, a mineral acid such as hydrochloric acid or phosphoric acid, or an organic acid such as acetic acid is used. The amount of the acid is not particularly limited, but is preferably based on the acetylenic halogenoester represented by the general formula [II]. It is 0.01 to 10 times mol.
さらに，本発明いおいては有機第４級アンモニウム塩
を使用することもできる。Further, in the present invention, an organic quaternary ammonium salt can be used.
かかる有機第４級アンモニウム塩としては例えば，テ
トラ−ｎ−ブチルアンモニウムブロミド，テトラ−ｎ−
ブチルアンモニウムクロリド，テトラ−ｎ−ペンチルア
ンモニウムブロミド，テトラ−ｎ−ペンチルアンモニウ
ムアイオダイド，ベンジルトリエチルアンモニウムブロ
ミド，ベンジルトリプロピルアンモニウムクロリド，ベ
ンジルトリプロピルアンモニウムアイオダイド，ドデシ
ルトリメチルアンモニウムブロミド，セチルトリメチル
アンモニウムクロリド等が挙げられる。Such organic quaternary ammonium salts include, for example, tetra-n-butylammonium bromide, tetra-n-
Butylammonium chloride, tetra-n-pentylammonium bromide, tetra-n-pentylammonium iodide, benzyltriethylammonium bromide, benzyltripropylammonium chloride, benzyltripropylammonium iodide, dodecyltrimethylammonium bromide, cetyltrimethylammonium chloride, etc. No.
本発明の反応温度は，通常５〜95℃，好ましくは10〜
80℃，より好ましくは20〜60℃で行われ，反応の終点は
通常，一般式〔II〕で示されるアセチレン性ハロゲノエ
ステル類を反応系から検出できなくなった時点をもって
決定される。The reaction temperature of the present invention is usually 5 to 95 ° C, preferably 10 to 95 ° C.
The reaction is carried out at 80 ° C, more preferably at 20 to 60 ° C, and the end point of the reaction is usually determined when the acetylenic halogenoester represented by the general formula [II] can no longer be detected from the reaction system.
反応終了後，反応混合物を通常の後処理，例えば濾
過，抽出，分液等の後，シリカゲルカラムクロマトグラ
フィーによる精製により，目的化合物である一般式〔II
I〕で示される２−フリルカルビノール誘導体を得るこ
とができる。After completion of the reaction, the reaction mixture is subjected to usual post-treatments, for example, filtration, extraction, liquid separation, and the like, followed by purification by silica gel column chromatography to obtain the target compound represented by the general formula [II
A 2-furylcarbinol derivative represented by the formula (I) can be obtained.
＜発明の効果＞ 本発明によれば従来の合成法で用いていた発火危険性
の高い試薬を使用することなく，フルフラール類〔Ｉ〕
と，容易に合成可能なアセチレン性ハロゲノエステル類
〔II〕とを，亜鉛と水の存在下２−フリルカルビノール
誘導体を工業的にも有利に製造することができる。<Effect of the Invention> According to the present invention, furfurals [I] can be obtained without using a reagent having a high risk of ignition used in a conventional synthesis method.
And an acetylenic halogeno ester [II] which can be easily synthesized, and a 2-furylcarbinol derivative can be industrially advantageously produced in the presence of zinc and water.
該誘導体は医農薬，とりわけプロスタグランディン中
間体として有用である。The derivatives are useful as medicinal and agricultural chemicals, especially as prostaglandin intermediates.
＜実施例＞ 以下，実施例により本発明をさらに詳細に説明する。<Example> Hereinafter, the present invention will be described in more detail with reference to examples.
実施例１ 窒素雰囲気下，フルフラール0.88g,トルエン0.87g,亜
鉛粉0.78g,テトラ−ｎ−ブチルアンモニウムブロミド0.
26g及び水7.8gの混合物に30〜35℃で塩化アンモニウム
1.13gを加えた。Example 1 Under a nitrogen atmosphere, furfural 0.88 g, toluene 0.87 g, zinc powder 0.78 g, tetra-n-butylammonium bromide.
Ammonium chloride in a mixture of 26 g and 7.8 g of water at 30-35 ° C
1.13g was added.
反応液を25℃まで冷却し,25〜30℃で７−ブロモ−５
−ヘプチン酸メチル1gを30分〜１時間かけて加えた。滴
下終了後，同温度で５時間撹拌した。The reaction solution is cooled to 25 ° C, and 7-bromo-5 is added at 25-30 ° C.
-1 g of methyl heptate was added over 30 minutes to 1 hour. After completion of the dropwise addition, the mixture was stirred at the same temperature for 5 hours.
反応終了後，反応液にトルエン200mlを加えて濾過
し，有機層を少量の５％炭酸水素ナトリウム水溶液，飽
和食塩水で洗浄後，硫酸マグネシウムで乾燥し，溶媒を
減圧下に留去して粗生成物を得た。更にこれをシリカゲ
ルクロマトグラフィーにより精製して８−（２フリル）
−８−ヒドロキシ−５−オクチン酸メチル0.62gを得
た。After completion of the reaction, 200 ml of toluene was added to the reaction solution, and the mixture was filtered. The organic layer was washed with a small amount of a 5% aqueous sodium hydrogen carbonate solution and saturated saline, dried over magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain a crude product. The product was obtained. This was further purified by silica gel chromatography to give 8- (2 furyl)
0.62 g of methyl -8-hydroxy-5-octoate was obtained.
実施例２ 窒素雰囲気下，フルフラール0.88g,トルエン0.87g,亜
鉛粉0.78g,テトラ−ｎ−ブチルアンモニウムブロミド0.
26g,水7.8g及び酢酸0.20gの混合物に,30〜35℃で７−ブ
ロモ−５−ヘプチン酸メチル1gを30分〜１時間かけて加
えた。滴下終了後，同温度で４時間撹拌した。Example 2 Under a nitrogen atmosphere, furfural 0.88 g, toluene 0.87 g, zinc powder 0.78 g, tetra-n-butylammonium bromide 0.1 g.
To a mixture of 26 g, 7.8 g of water and 0.20 g of acetic acid was added 1 g of methyl 7-bromo-5-heptinate at 30-35 ° C over 30 minutes to 1 hour. After completion of the dropwise addition, the mixture was stirred at the same temperature for 4 hours.
反応終了後，実施例１に準じて後処理を行い,8−（２
フリル）−８−ヒドロキシ−５−オクチン酸メチル0.71
gを得た。After completion of the reaction, post-treatment was carried out according to Example 1, and 8- (2
Methyl (furyl) -8-hydroxy-5-octate 0.71
g was obtained.
実施例３ ７−ブロモ−５−ヘプチン酸メチルに代えて８−ブロ
モ−６−オクチン酸メチルを用いる以外は実施例１に準
じて反応及び後処理をして,9−（２−フリル）−９−ヒ
ドロキシ−６−ノニン酸メチル0.67gを得た。Example 3 The reaction and post-treatment were conducted in the same manner as in Example 1 except that methyl 8-bromo-6-octoate was used instead of methyl 7-bromo-5-heptinate to give 9- (2-furyl)- 0.67 g of methyl 9-hydroxy-6-nonate was obtained.
実施例４ フルフラールに代えて４−メチルフルフラールを用い
る以外は実施例１に準じて反応及び後処理して,8−（４
−メチル−２−フリル）−８−ヒドロキシ−５−オクチ
ン酸メチル0.51gを得た。Example 4 A reaction and a post-treatment were carried out in the same manner as in Example 1 except that 4-methylfurfural was used instead of furfural to obtain 8- (4
0.51 g of methyl (methyl-2-furyl) -8-hydroxy-5-octoate was obtained.
───────────────────────────────────────────────────── フロントページの続き (72)発明者 南井 正好 大阪府大阪市此花区春日出中３丁目１番 98号 住友化学工業株式会社内 (56)参考文献 特開 昭62−29568（ＪＰ，Ａ) 特開 昭62−281875（ＪＰ，Ａ) 特開 昭63−30480（ＪＰ，Ａ) 特開 昭63−33372（ＪＰ，Ａ) ────────────────────────────────────────────────── ─── Continuation of front page (72) Inventor Masayoshi Minami 3-1-198, Kasuganaka, Konohana-ku, Osaka-shi, Japan Sumitomo Chemical Co., Ltd. (56) References JP-A-62-29568 (JP, A) JP-A-62-281875 (JP, A) JP-A-63-30480 (JP, A) JP-A-63-33372 (JP, A)
Claims (4)
す。） で示されるフルフラール類と，一般式 （式中,Xはハロゲン原子を表わし、R2は水素原子または
低級アルギル基を表わす。ｎは２〜４の整数を表わ
す。） で示されるアセチレン性ハロゲノエステル類とを，亜鉛
及び水の存在下に反応させることを特徴とする一般式 （式中，R1，R2及びｎは前記と同じ意味を表わす。） で示される２−フリルカルビノール誘導体の製造法。(1) General formula (In the formula, R 1 represents a hydrogen atom or a lower alkyl group.) (Wherein, X represents a halogen atom, R 2 represents a hydrogen atom or a lower argyl group, and n represents an integer of 2 to 4), and an acetylenic halogenoester represented by the following formula: General formula characterized by reacting below (In the formula, R 1 , R 2 and n have the same meanings as described above.) A method for producing a 2-furylcarbinol derivative represented by the formula:
せる請求項１記載の製造法。2. The process according to claim 1, wherein the reaction is carried out in the presence of an ammonium halide.
造法。3. The process according to claim 1, wherein the reaction is carried out in the presence of an acid.
る請求項２または３記載の製造法。4. The process according to claim 2, wherein the reaction is carried out in the presence of a quaternary ammonium salt.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP21314689A JP2906062B2 (en) | 1989-08-18 | 1989-08-18 | Method for producing 2-furylcarbinol derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP21314689A JP2906062B2 (en) | 1989-08-18 | 1989-08-18 | Method for producing 2-furylcarbinol derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH0377878A JPH0377878A (en) | 1991-04-03 |
| JP2906062B2 true JP2906062B2 (en) | 1999-06-14 |
Family
ID=16634341
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP21314689A Expired - Lifetime JP2906062B2 (en) | 1989-08-18 | 1989-08-18 | Method for producing 2-furylcarbinol derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2906062B2 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR071312A1 (en) | 2008-04-09 | 2010-06-09 | Scinopharm Taiwan Ltd | PROCESS FOR THE PREPARATION OF PROSTAGLANDINE ANALOGS AND THEIR INTERMEDIARIES |
-
1989
- 1989-08-18 JP JP21314689A patent/JP2906062B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0377878A (en) | 1991-04-03 |
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