JPS6130571A - Preparation of 3-phenyl-4-cyanopyrrole - Google Patents
Preparation of 3-phenyl-4-cyanopyrroleInfo
- Publication number
- JPS6130571A JPS6130571A JP59150619A JP15061984A JPS6130571A JP S6130571 A JPS6130571 A JP S6130571A JP 59150619 A JP59150619 A JP 59150619A JP 15061984 A JP15061984 A JP 15061984A JP S6130571 A JPS6130571 A JP S6130571A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- group
- lower alkyl
- tosylmethyl isocyanide
- reaction
- 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.)
- Granted
Links
Landscapes
- Pyrrole Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
（産業上の利用分野）
本発明は医薬、農薬の中間体として有用な一般式
（式中、Ｘはハロゲン原子、低級アルキル基、低級ハロ
アルキル基、アルキルアミノ基、アルコキシル基、ニト
ロ基、シアン基及びメチレンジオキ７基の群から選ばれ
た異種又は同種の置換基を、ｎｉｔ：０，１又は２を示
す。）で表わされるピロール誘導体の製造方法に関する
ものである。DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention describes the general formula (wherein X is a halogen atom, a lower alkyl group, a lower haloalkyl group, an alkylamino group, an alkoxyl The present invention relates to a method for producing a pyrrole derivative represented by a different or similar substituent selected from the group consisting of a nitro group, a cyan group, a nitro group, a cyan group, and a methylene dioxy group (nit: 0, 1, or 2).
上記ピロール誘導体は、例えば１位にアシル化すること
により特開昭５６−７９６７２．５５−５１０６６．５
５−５７５０８等に記載の農園芸用殺菌剤の中間体とし
て有用である。The above-mentioned pyrrole derivative can be obtained by, for example, acylating at the 1-position,
It is useful as an intermediate for agricultural and horticultural fungicides described in 5-57508 and the like.
（従来の技術）
上記ピロール誘導体の製造方法としては、Ｔｅｔｒａｈ
ｅｄｒｏｎ Ｌｅｔｔｅｒｓ Ｎｏ、５２、ｐｐ５３３
７−５３４０．１９７２に記載の下記反応式に示す方法
が知られている。(Prior art) As a method for producing the above-mentioned pyrrole derivative, Tetrah
edron Letters No. 52, pp533
The method shown in the following reaction formula described in No. 7-5340.1972 is known.
ｎ
（ＩＶ） （Ｉｆ）
ｎ
しかしながら該製造方法は３５チと低収率のため化合物
（ｍ）を得るには繁雑な精製工程が必要であるばかりで
なく、原料化合物（■）は例えば、一般式
（式中、Ｘ及びｎは前記と同じ意味を示し、ＲはＨ又は
低級アルキル基を示す。）で表わされるα−シアノ桂皮
酸類を脱炭酸することによシ得られるが、脱炭酸の条件
が厳しかったシ、真空蒸留又は再結晶等のｆ製工程が必
要である等工業原料として好ましいものではなく、該製
造方法は工業的製造方法としては好ましいものではなか
った。n (IV) (If) n However, this production method not only requires a complicated purification process to obtain compound (m) due to the low yield of 35%, but also the raw material compound (■), for example, It can be obtained by decarboxylating α-cyanocinnamic acids represented by the formula (wherein, X and n have the same meanings as above, and R represents H or a lower alkyl group); The production method was not preferred as an industrial raw material because the conditions were severe and production steps such as vacuum distillation or recrystallization were necessary.
（発明が解決しようとする問題点）
□本発明者らは入手しやすい原料を用いて収率よく前記
ピロール誘導体を製造する方法について検討を重ね本発
明を完成した。(Problems to be Solved by the Invention) □The present inventors have completed the present invention after repeated studies on a method for producing the above-mentioned pyrrole derivatives in good yield using readily available raw materials.
（問題点を解決するための手段）
本発明は一般式（１）で表わされるα−シアン桂皮酸類
と式（１）で表わされるトシルメチルイソシアニドとを
有機溶媒中、塩基又は触媒の存在下、反応させることを
特徴とする一般式（ＩＩＩ）で表わされるピロール誘導
体の製造方法である。(Means for Solving the Problems) The present invention provides an α-cyaninnamic acid represented by the general formula (1) and a tosylmethyl isocyanide represented by the formula (1) in an organic solvent in the presence of a base or a catalyst. This is a method for producing a pyrrole derivative represented by general formula (III), which is characterized by carrying out a reaction.
塩基としては水素化ナトリウム、ナトリウムアルコキシ
ド、カリウムアルコキシド、金属ナトリウム、水酸化ナ
トリウム、水酸化カリウム、炭酸カリウムあるいは炭酸
ナトリウム等の有機又は無機塩基が用いられる。As the base, an organic or inorganic base such as sodium hydride, sodium alkoxide, potassium alkoxide, metallic sodium, sodium hydroxide, potassium hydroxide, potassium carbonate or sodium carbonate is used.
有機溶媒としてれ塩基として水素化ナトリウム、アルコ
キシド、金属ナトリウム等を用いる場合にはベンゼン、
トルエン、エーテル、テトラヒドロフラン、ジメトキシ
エタン等の非水素溶媒を用いることができるが、好まし
くはジメトキシエタン、ジメチルスルホキシド、ジメチ
ルホルムアミド等のアニオン安定化溶媒を用いるか又は
トシルメチルイソシアニドと当量のジメチルスルホキシ
ドもしくはジメチルホルムアミドを添加した混合溶媒を
用いるのが良い。塩基として水酸化ナトリウム、水酸化
カリウム、炭酸カリウム、炭酸ナトリウムを用いる場合
は前記の溶媒の他にメタノール、エタノール又はメタノ
ール、エタノールとノ１０ゲン系溶媒、例えば塩化メチ
レンとの混合溶媒等を用いるξともできる。触媒として
はトシルメチルイソシアニドと錯体を形成する銅化合物
、例えば酸化第−銅等が用いられる。When using sodium hydride, alkoxide, metallic sodium, etc. as an organic solvent and as a base, benzene,
Non-hydrogen solvents such as toluene, ether, tetrahydrofuran, dimethoxyethane can be used, but preferably anionic stabilizing solvents such as dimethoxyethane, dimethyl sulfoxide, dimethyl formamide are used, or dimethyl sulfoxide or dimethyl in an amount equivalent to tosylmethyl isocyanide is used. It is preferable to use a mixed solvent to which formamide is added. When sodium hydroxide, potassium hydroxide, potassium carbonate, or sodium carbonate is used as a base, in addition to the above-mentioned solvents, methanol, ethanol, methanol, a mixed solvent of ethanol and a solvent such as methylene chloride, etc. are used. You can also do it. As the catalyst, a copper compound that forms a complex with tosylmethylisocyanide, such as cupric oxide, is used.
反応温度は、使用する塩基、溶媒等により異なるが通常
−１Ｏ°〜１００℃、好ましくは０℃〜４０℃の緩和な
条件下で行われる。The reaction temperature varies depending on the base, solvent, etc. used, but it is usually carried out under mild conditions of -10° to 100°C, preferably 0°C to 40°C.
（作 用）
本発明の製造方法は緩和な条件で反応が進行することか
ら、公知の製造方法とは全く異なった以下に示す反応機
構で反応が進行するものと思われる。(Function) Since the reaction proceeds under mild conditions in the production method of the present invention, it is thought that the reaction proceeds according to the reaction mechanism shown below, which is completely different from known production methods.
（実施例）
以下、実施例を挙げて本発明について更に詳しく説明す
るが本発明の製造方法はこれら実施例に限定されるもの
ではない。(Examples) Hereinafter, the present invention will be explained in more detail with reference to Examples, but the manufacturing method of the present invention is not limited to these Examples.
実施例１
α−シアン桂皮酸エチルエステル１０．０６Ｆ（５０，
０ミリモル）とトシルメチルイソシアニ）’ Ｉ Ｑ：
２５ｆ（５２，５ミリモル）を乾燥したジメトキシエタ
ン８０ｍ１！に溶かし、その溶液をＮ２気流下５０チＮ
ａＨ２，８８ｒ（６０，０ミリモル）の乾燥したジメト
キシエタン５ｏ＋ｎＱの懸濁液Ｋ Ｏ’〜５℃の間で滴
下し反応させた。Example 1 α-cyanocinnamic acid ethyl ester 10.06F (50,
0 mmol) and tosylmethyl isocyanin)' IQ:
80 ml of dimethoxyethane containing 25 f (52.5 mmol)! The solution was heated to 50 N under a stream of N2.
A suspension of aH2,88r (60,0 mmol) in dry dimethoxyethane 5o+nQ was added dropwise to react between KO' and 5°C.
滴下後室温で１時間攪拌し反応を完結させた抜水５０ｍ
ｆｆ１を加え１０チＨＣ１でｐＩ（８に中和し７た。そ
の後ジメトキシエタンを減圧留去し、次いで水１００ｍ
ｅを加え３０分間攪拌の後析出した結晶を濾過し、水及
びトルエンで洗浄後乾燥して３−フェニル−４−シアノ
ピロール７４８１を得た。収率８８．９％ ｍｐｌ
２９〜１ ３０℃実施例２
Ｃ７゜
α−シアノ−Ｏ−クロル桂皮酸エチルエステル１１．７
８ ｆ （５０，０ミリモル）をエタノールｓｏｍｅに
溶かし００Ｃ〜３°Ｃに冷却の後ナトリウムエトキシド
４．０８ ｔ （６０，０ミＩＪモル）を加えた。次い
でトシルメチルイソシアニド１０．２５ ｔ （５２，
５ミリモル）を塩化メチレン？０ｎｌに溶かした溶液を
００〜３℃の間で滴下し反応させ、同温度で１時間攪拌
し反応を完結させた。その抜水５０ ｍｌ＋、を加え１
０％ ＨＣｌでｐＨ８とした後塩化メチレン及びエタノ
ールを減圧留去し、次いで水１００ｍ１を加え３０分間
撹拌の後析出した結晶を濾過し、水で洗浄後乾燥シて３
− （２−り四ルフェニル）−４−シアンビロール９．
９３２を得た。収率９８０チ ｍｐ１３８〜１３９ ℃
実施例３
？メトキシエタン１００社に水酸化カリウム１２゜６：
ｌ’ （２２５，０ミリモル）を加え冷却下０°〜１０
℃でα−シアノ−３，４−ジメトキシ桂皮酸１１．６６
Ｆ（５０，０ミリモル）を分割添加し、同温度で３０分
間攪拌した。次いでトシルメチルイソシアニド１０．２
５ ｔ （５２，５ミリモル）をジットキシエタン□
Ｑ ｍＱに溶かした溶液を室温で１時間で滴下し、滴下
後２時間室温で攪拌し反応完結させた。その抜水７０ｍ
１を加え１０％ＨＣ１でｐＨ８とした後ジメトキシエタ
ンを減圧留去し、次いで水８０ｍ１を加え３０分間攪拌
の後析出した結晶を濾過し、水で洗浄後乾燥して３−（
３，４−ジメトキシフェニル）−４−シアノピロールｉ
０．５Ｏｆを得た。収率９２０％ ｍｐ２１２〜２１４
℃
実施例４
■
メタノール８０艷に炭酸カリウム２０．７３９（１５０
，０ミリモル）とα−シアノ−ｐ−シアノ桂皮酸９゜９
１ｆ（５０，０ミＩＪモル）を加え室温で３０分間攪拌
した。次いでトシルメチルイソシアニド１０．２５ｆｃ
５２．５ミリモル）を塩化メチレン７９ｉｉＪＣ溶かし
た溶液を３０°〜４０℃の間で滴下し、滴下後４０℃で
３時間攪拌し反応させた。その抜水５０威を加え１０チ
ＨＣｔでｐＨ８とした後塩化メチレン、及びメタノール
を減圧留去し、次いで水１００ｍ１を加え３０分間攪拌
の後析出した結晶を濾過し、水で洗浄後乾燥して３−（
４−シアノフェニル）−４−シアノピロール７８３ｔを
得た。収率８１０５チ ｍｐｌ ７０〜１７２℃
実施例５
水酸化カリウム１２．６２ ｆ （２２５，０ミリモル
）をメタノール８０ＴｄｌＫ溶かし、冷却下０°〜１０
℃でα−シアノ−２，３−ジクロル桂皮酸を添加し、同
温度で３０分間攪拌した。次いでトシルメチルイソシア
ニド１０．２５ ｔ （５２，５ミリモル）を塩化メチ
レン７０艷に溶かした溶液を００〜５℃の間で滴下し、
滴下後３０分間同温度で攪拌し反応を完結させた。その
抜水５０ｍ１を加え１０チＨＣＬでｐＨ８とした数基化
メチレン、及びメタノールを減圧留去し、次いで水１０
０ｍｆｆ１を加え３０分間攪拌の後析出した結晶を濾過
し、水で洗浄後乾燥して３−（２，３−ジク鴛ルフェニ
ル）−４−シアノピロール１１７３ ｔを得た。収率９
９．０ ％ ｍｐｌ ５２〜１５３℃
実施例６〜１８
実施例５と同様な方法により反応を行なった。After dropping, stir at room temperature for 1 hour to complete the reaction.
ff1 was added and the pI was neutralized to 8 with 10 ml of HCl (7). Dimethoxyethane was then distilled off under reduced pressure,
After stirring for 30 minutes, the precipitated crystals were filtered, washed with water and toluene, and dried to obtain 3-phenyl-4-cyanopyrrole 7481. Yield 88.9% mpl
29-1 30℃ Example 2 C7゜α-cyano-O-chlorocinnamic acid ethyl ester 11.7
8 f (50.0 mmol) was dissolved in some ethanol and cooled to 00°C to 3°C, and then 4.08 t (60.0 mmol) of sodium ethoxide was added. Then 10.25 t of tosylmethyl isocyanide (52,
5 mmol) in methylene chloride? A solution dissolved in 0 nl was added dropwise at a temperature of 00 to 3°C to react, and the reaction was completed by stirring at the same temperature for 1 hour. Add 50 ml of the drained water + 1
After adjusting the pH to 8 with 0% HCl, methylene chloride and ethanol were distilled off under reduced pressure. Then, 100 ml of water was added and after stirring for 30 minutes, the precipitated crystals were filtered, washed with water, and dried for 3
- (2-ri-tetraphenyl)-4-cyanvirol9.
I got 932. Yield: 980 cm mp: 138-139°C Example 3? Potassium hydroxide 12°6 to 100 methoxyethane:
l' (225,0 mmol) and cooled from 0° to 10
α-cyano-3,4-dimethoxycinnamic acid 11.66 at °C
F (50.0 mmol) was added in portions and stirred at the same temperature for 30 minutes. Then tosylmethylisocyanide 10.2
5 t (52.5 mmol) of ditoxyethane□
A solution dissolved in Q mQ was added dropwise at room temperature over 1 hour, and after the dropwise addition, the mixture was stirred at room temperature for 2 hours to complete the reaction. The drainage water is 70m
1 and adjusted to pH 8 with 10% HCl, dimethoxyethane was distilled off under reduced pressure, then 80 ml of water was added and after stirring for 30 minutes, the precipitated crystals were filtered, washed with water and dried to give 3-(
3,4-dimethoxyphenyl)-4-cyanopyrrole i
Obtained 0.5Of. Yield 920% mp212-214
°C Example 4 ■ Potassium carbonate 20.739 (150
, 0 mmol) and α-cyano-p-cyanocinnamic acid 9°9
1f (50.0 mmol) was added and stirred at room temperature for 30 minutes. Then tosylmethylisocyanide 10.25fc
A solution of 52.5 mmol) dissolved in 79iiJC of methylene chloride was added dropwise between 30° and 40°C, and after the dropwise addition, the mixture was stirred at 40°C for 3 hours to react. After adding 50 ml of water and adjusting the pH to 8 with 10 HCt, methylene chloride and methanol were distilled off under reduced pressure. Next, 100 ml of water was added and after stirring for 30 minutes, the precipitated crystals were filtered, washed with water, and dried. 3-(
783t of 4-cyanophenyl)-4-cyanopyrrole was obtained. Yield 8105 cmpl 70~172°C Example 5 Potassium hydroxide 12.62 f (225.0 mmol) was dissolved in methanol 80 TdlK and cooled at 0°~10°C.
α-Cyano-2,3-dichlorocinnamic acid was added at °C, and the mixture was stirred at the same temperature for 30 minutes. Next, a solution of 10.25 t (52.5 mmol) of tosylmethyl isocyanide dissolved in 70 mmol of methylene chloride was added dropwise between 00 and 5°C.
After the dropwise addition, the mixture was stirred at the same temperature for 30 minutes to complete the reaction. 50 ml of the drained water was added, and the pH was adjusted to 8 with 10 ml of HCl. The methylene and methanol were distilled off under reduced pressure, and then 10 ml of water was added.
After adding 0mff1 and stirring for 30 minutes, the precipitated crystals were filtered, washed with water, and dried to obtain 1173 t of 3-(2,3-dichlorophenyl)-4-cyanopyrrole. Yield 9
9.0% mpl 52-153°C Examples 6-18 Reactions were carried out in the same manner as in Example 5.
結果を表−１に示す。The results are shown in Table-1.
（発明の効果）
上記実施例からも明らかなように本発明の製造方法は緩
和な条件で反応が進行し、しかも目的物がほぼ定量的に
得られることから精製工程もはとんど必要のない工業的
に非常に優れたピロール銹導体の製造方法である。(Effects of the Invention) As is clear from the above examples, the production method of the present invention allows the reaction to proceed under mild conditions, and moreover, the target product can be obtained almost quantitatively, so no purification steps are necessary. This is an industrially superior manufacturing method for pyrrole conductors.
Claims (3)
アルキル基、アルキルアミノ基、アルコキシル基、ニト
ロ基、シアノ基及びメチレンジオキシ基の群から選ばれ
た異種又は同種の置換基を、ｎは０、１又は２を、Ｒは
Ｈ又は低級アルキル基を示す。）で表わされるα−シア
ノ桂皮酸類と、式▲数式、化学式、表等があります▼（
II） で表わされるトシルメチルイソシアニドとを反応させる
ことを特徴とする一般式 ▲数式、化学式、表等があります▼（III） （式中、Ｘ及びｎは前記と同じ意味を示す。）で表わさ
れるピロール誘導体の製造方法。(1) General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (I) (In the formula, X is a halogen atom, lower alkyl group, lower haloalkyl group, alkylamino group, alkoxyl group, nitro group, cyano group, and methylenedi α-cyanocinnamic acids represented by different or similar substituents selected from the group of oxy groups, where n is 0, 1 or 2, and R is H or a lower alkyl group; There are chemical formulas, tables, etc.▼(
II) General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (III) (In the formula, X and n have the same meanings as above.) A method for producing a pyrrole derivative.
囲第１項記載の製造方法。(2) The manufacturing method according to claim 1, wherein the reaction is carried out in the presence of a base in an organic solvent.
囲第１項記載の製造方法。(3) The manufacturing method according to claim 1, wherein the reaction is carried out in an organic solvent in the presence of a catalyst.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59150619A JPS6130571A (en) | 1984-07-20 | 1984-07-20 | Preparation of 3-phenyl-4-cyanopyrrole |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59150619A JPS6130571A (en) | 1984-07-20 | 1984-07-20 | Preparation of 3-phenyl-4-cyanopyrrole |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6130571A true JPS6130571A (en) | 1986-02-12 |
| JPH0432064B2 JPH0432064B2 (en) | 1992-05-28 |
Family
ID=15500824
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP59150619A Granted JPS6130571A (en) | 1984-07-20 | 1984-07-20 | Preparation of 3-phenyl-4-cyanopyrrole |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6130571A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4960789A (en) * | 1987-11-09 | 1990-10-02 | Bayer Aktiengesellschaft | 3-cyano-4-phenyl-pyrroles as fungicides |
| WO1991005769A1 (en) * | 1989-10-17 | 1991-05-02 | Nippon Soda Co., Ltd. | Novel pyrrole monomer, process for preparing the same, and functional polymer film |
-
1984
- 1984-07-20 JP JP59150619A patent/JPS6130571A/en active Granted
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4960789A (en) * | 1987-11-09 | 1990-10-02 | Bayer Aktiengesellschaft | 3-cyano-4-phenyl-pyrroles as fungicides |
| WO1991005769A1 (en) * | 1989-10-17 | 1991-05-02 | Nippon Soda Co., Ltd. | Novel pyrrole monomer, process for preparing the same, and functional polymer film |
| US5278295A (en) * | 1989-10-17 | 1994-01-11 | Nippon Soda Co., Ltd. | Pyrrole monomer |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0432064B2 (en) | 1992-05-28 |
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