JPH0920715A - Production of 2-substituted-1,3-indanedione derivative - Google Patents
Production of 2-substituted-1,3-indanedione derivativeInfo
- Publication number
- JPH0920715A JPH0920715A JP7174905A JP17490595A JPH0920715A JP H0920715 A JPH0920715 A JP H0920715A JP 7174905 A JP7174905 A JP 7174905A JP 17490595 A JP17490595 A JP 17490595A JP H0920715 A JPH0920715 A JP H0920715A
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- carbon atoms
- group
- alkyl group
- alkyl
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Classifications
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は、医薬および農薬の中間
体として有用な２置換−１，３−インダンジオンの製造
法に関する。TECHNICAL FIELD The present invention relates to a method for producing a disubstituted-1,3-indandione which is useful as an intermediate for medicines and agricultural chemicals.
【０００２】[0002]
【従来の技術および発明が解決しようとする課題】従
来、２置換−１，３インダンジオン誘導体の製造法とし
ては、α位にメチレンを持つケトンとフタル酸エステル
誘導体とを塩基の存在下反応させる製造法（W. A. Mosh
er et. al., J. Org. Chem., 36, 1561 (1971)）、α位
にメチレンを持つエステルとフタル酸エステル誘導体と
を金属ナトリウムの存在下反応させる製造法（Koelsch,
Byers, J. Am. Chem. Soc., 62, 560 (1940) ）などが
知られている。しかしながら、上記製造法では、２置換
−１，３−インダンジオン誘導体の収率がフタル酸エス
テル誘導体に対し３０〜６０％と低く、また工業的に使
用し難い金属ナトリウムを用いるといった点で、工業的
製造法として満足し難いものであった。2. Description of the Related Art Conventionally, as a method for producing a disubstituted-1,3 indandione derivative, a ketone having a methylene at the α-position is reacted with a phthalate derivative in the presence of a base. Manufacturing method (WA Mosh
er et. al., J. Org. Chem., 36 , 1561 (1971)), a method of reacting an ester having a methylene at the α-position with a phthalate derivative in the presence of metallic sodium (Koelsch,
Byers, J. Am. Chem. Soc., 62 , 560 (1940)) are known. However, in the above-mentioned production method, the yield of the 2-substituted-1,3-indandione derivative is as low as 30 to 60% with respect to the phthalate ester derivative, and metal sodium, which is industrially difficult to use, is used. It was hard to be satisfied as an industrial manufacturing method.
【０００３】[0003]
【課題を解決するための手段】本発明者らは、上記課題
を解決するために鋭意検討した結果、α位にメチレン基
を持つエステルとフタル酸エステル誘導体とを塩基の存
在下反応させることにより、２置換−１，３−インダン
ジオン誘導体が高収率で得られることを見いだし、本発
明を完成するに至った。Means for Solving the Problems As a result of intensive studies for solving the above problems, the present inventors have found that an ester having a methylene group at the α-position is reacted with a phthalate ester derivative in the presence of a base. It was found that the 2-substituted-1,3-indandione derivative was obtained in high yield, and the present invention was completed.
【０００４】すなわち、本発明の要旨は、下記一般式
（１）That is, the gist of the present invention is the following general formula (1):
【０００５】[0005]
【化７】Ｒ1 ＣＨ2 ＣＯ2 Ｒ2 （１）Embedded image R 1 CH 2 CO 2 R 2 (1)
【０００６】（上記式中、Ｒ1 は炭素数１〜１０のアル
キル基、炭素数２〜１０のアルケニル基または炭素数２
〜１０のアルキニル基を表し、Ｒ2 は炭素数１〜４のア
ルキル基を表す）で表されるエステル類と、下記一般式
（２）(In the above formula, R 1 is an alkyl group having 1 to 10 carbon atoms, an alkenyl group having 2 to 10 carbon atoms or 2 carbon atoms.
An alkynyl group of 10 to 10 and R 2 represents an alkyl group of 1 to 4 carbon atoms) and the following general formula (2)
【０００７】[0007]
【化８】 Embedded image
【０００８】（上記式中、Ｒ3 は炭素数１〜４のアルキ
ル基を表し、Ｒ4 、Ｒ5 、Ｒ6 およびＲ7 はそれぞれ独
立して、水素原子、炭素数１〜１０のアルキル基、炭素
数２〜１０のアルケニル基、炭素数２〜１０のアルキニ
ル基、炭素数１〜１０のアルコキシル基またはハロゲン
原子を表す）で表されるフタル酸エステル誘導体とを塩
基の存在下、反応させることを特徴とする、下記一般式
（３）(In the above formula, R 3 represents an alkyl group having 1 to 4 carbon atoms, and R 4 , R 5 , R 6 and R 7 are each independently a hydrogen atom or an alkyl group having 1 to 10 carbon atoms. Represents an alkenyl group having 2 to 10 carbon atoms, an alkynyl group having 2 to 10 carbon atoms, an alkoxyl group having 1 to 10 carbon atoms or a halogen atom) in the presence of a base. Which is characterized by the following general formula (3)
【０００９】[0009]
【化９】 Embedded image
【００１０】（上記式中、Ｒ1 は炭素数１〜１０のアル
キル基、炭素数２〜１０のアルケニル基、炭素数２〜１
０のアルキニル基を表し、Ｒ4 、Ｒ5 、Ｒ6 およびＲ7
はそれぞれ独立して、水素原子、炭素数１〜１０のアル
キル基、炭素数２〜１０のアルケニル基、炭素数２〜１
０のアルキニル基、炭素数１〜１０のアルコキシル基ま
たはハロゲン原子を表す）で表される２置換−１，３−
インダンジオン誘導体の製造法に存する。(In the above formula, R 1 is an alkyl group having 1 to 10 carbon atoms, an alkenyl group having 2 to 10 carbon atoms, and 2-1 to 2 carbon atoms.
Represents an alkynyl group of 0 and represents R 4 , R 5 , R 6 and R 7
Are each independently a hydrogen atom, an alkyl group having 1 to 10 carbon atoms, an alkenyl group having 2 to 10 carbon atoms, or 2-1 to 2 carbon atoms.
0 represents an alkynyl group, an alkoxyl group having 1 to 10 carbon atoms or a halogen atom).
It exists in a method for producing an indandione derivative.
【００１１】以下、本発明を詳細に説明する。本発明で
は、下記一般式（１）Hereinafter, the present invention will be described in detail. In the present invention, the following general formula (1)
【００１２】[0012]
【化１０】Ｒ1 ＣＨ2 ＣＯ2 Ｒ2 （１）Embedded image R 1 CH 2 CO 2 R 2 (1)
【００１３】（上記式中、Ｒ1 は炭素数１〜１０のアル
キル基、炭素数２〜１０のアルケニル基またはアルキニ
ル基を表し、Ｒ2 は炭素数１〜４のアルキル基を表す）
で表されるエステル類と、下記一般式（２）(In the above formula, R 1 represents an alkyl group having 1 to 10 carbon atoms, an alkenyl group having 2 to 10 carbon atoms or an alkynyl group, and R 2 represents an alkyl group having 1 to 4 carbon atoms)
And an ester represented by the following general formula (2)
【００１４】[0014]
【化１１】 Embedded image
【００１５】（上記式中、Ｒ3 は炭素数１〜４のアルキ
ル基を表し、Ｒ4 、Ｒ5 、Ｒ6 およびＲ7 はそれぞれ独
立して、水素原子、炭素数１〜１０のアルキル基、炭素
数２〜１０のアルケニル基、炭素数２〜１０のアルキニ
ル基、炭素数１〜１０のアルコキシル基またはハロゲン
原子を表す）で表されるフタル酸エステル誘導体とを、
無溶媒あるいは溶媒に懸濁、溶解した塩基中に加熱下滴
下し、滴下終了後、さらに加熱、反応させ、反応終了
後、水を加え反応を停止し、有機溶媒で洗浄後、水層を
酸性とし有機溶媒と接触させ有機層を分離、濃縮するこ
とにより、下記一般式（３）(In the above formula, R 3 represents an alkyl group having 1 to 4 carbon atoms, and R 4 , R 5 , R 6 and R 7 are each independently a hydrogen atom or an alkyl group having 1 to 10 carbon atoms. Represents an alkenyl group having 2 to 10 carbon atoms, an alkynyl group having 2 to 10 carbon atoms, an alkoxyl group having 1 to 10 carbon atoms, or a halogen atom).
After dropping dropwise with heating in a solvent-free or solvent-suspended or dissolved base, further heat and react after the addition, after the reaction is complete, add water to stop the reaction, wash with an organic solvent, and then acidify the aqueous layer. By contacting with an organic solvent and separating and concentrating the organic layer, the following general formula (3)
【００１６】[0016]
【化１２】 Embedded image
【００１７】（上記式中、Ｒ1 は炭素数１〜１０のアル
キル基、炭素数２〜１０のアルケニル基、炭素数２〜１
０のアルキニル基を表し、Ｒ4 、Ｒ5 、Ｒ6 およびＲ7
はそれぞれ独立して、水素原子、炭素数１〜１０のアル
キル基、炭素数２〜１０のアルケニル基、炭素数２〜１
０のアルキニル基、炭素数１〜１０のアルコキシル基ま
たはハロゲン原子を表す）で表される２置換−１，３−
インダンジオン誘導体を製造する。(In the above formula, R 1 is an alkyl group having 1 to 10 carbon atoms, an alkenyl group having 2 to 10 carbon atoms, or 2-1 to 2 carbon atoms.
Represents an alkynyl group of 0 and represents R 4 , R 5 , R 6 and R 7
Are each independently a hydrogen atom, an alkyl group having 1 to 10 carbon atoms, an alkenyl group having 2 to 10 carbon atoms, or 2-1 to 2 carbon atoms.
0 represents an alkynyl group, an alkoxyl group having 1 to 10 carbon atoms or a halogen atom).
An indandione derivative is produced.
【００１８】上記式において、炭素数１〜１０のアルキ
ル基としては、メチル基、エチル基、 プロピル基、イ
ソプロピル基、ブチル基、イソブチル基、ペンチル基、
ネオペンチル基、ヘキシル基、２−メチル−ヘキシル
基、ヘプチル基、オクチル基、デシル基等が挙げられ
る。炭素数２〜１０のアルケニル基としては、エテニル
基、１−プロペニル基、１−ブテニル基、１，３−ブタ
ジエニル基、１−ペンテニル基、２−ペンテニル基、１
−ヘキセニル基、２−エチル−２−ブテニル基、２−オ
クテニル基、（４−エテニル）−５−ヘキセニル基、２
−デセニル基、炭素数２〜１０のアルキニル基として
は、エチニル基、１−プロピニル基、１−ブチニル基、
１−ペンチニル基、３−ペンチニル基、１−ヘキシニル
基、２−エチル-２−ブチニル基、２−オクチニル基、
（４−エチニル）−５−ヘキシニル基、２−デシニル基
等が挙げられる。炭素数１〜４のアルキル基としては、
メチル基、エチル基、プロピル基、イソプロピル基、ブ
チル基、イソブチル基、sec-ブチル基が挙げられる。炭
素数１〜１０のアルコキシル基としては、メトキシ基、
エトキシ基等が挙げられる。ハロゲン原子としては、フ
ッ素原子、塩素原子、臭素原子、沃素原子等が挙げられ
る。In the above formula, as the alkyl group having 1 to 10 carbon atoms, methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, pentyl group,
Examples include neopentyl group, hexyl group, 2-methyl-hexyl group, heptyl group, octyl group, decyl group and the like. Examples of the alkenyl group having 2 to 10 carbon atoms include ethenyl group, 1-propenyl group, 1-butenyl group, 1,3-butadienyl group, 1-pentenyl group, 2-pentenyl group, 1
-Hexenyl group, 2-ethyl-2-butenyl group, 2-octenyl group, (4-ethenyl) -5-hexenyl group, 2
-The decenyl group and the alkynyl group having 2 to 10 carbon atoms include an ethynyl group, a 1-propynyl group, a 1-butynyl group,
1-pentynyl group, 3-pentynyl group, 1-hexynyl group, 2-ethyl-2-butynyl group, 2-octynyl group,
(4-ethynyl) -5-hexynyl group, 2-decynyl group and the like can be mentioned. As an alkyl group having 1 to 4 carbon atoms,
Examples thereof include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, and a sec-butyl group. As the alkoxyl group having 1 to 10 carbon atoms, a methoxy group,
Examples thereof include an ethoxy group. Examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.
【００１９】本発明において、Ｒ1 としては、炭素数１
〜１０のアルキル基が好ましく、さらに好ましくは炭素
数１〜４のアルキル基である。Ｒ2 としては、炭素数１
〜４のアルキル基、さらに好ましくは炭素数１〜２のア
ルキル基である。Ｒ4 〜Ｒ7としては、水素原子、炭素
数１〜１０のアルキル基およびハロゲン原子が好まし
く、さらに好ましくは水素原子、炭素数１〜４のアルキ
ル基およびハロゲン原子であり、特に好ましくは水素原
子である。In the present invention, R 1 has 1 carbon atom.
It is preferably an alkyl group having 10 to 10, more preferably an alkyl group having 1 to 4 carbon atoms. R 2 has 1 carbon atom
Is an alkyl group having 4 to 4 carbon atoms, and more preferably an alkyl group having 1 to 2 carbon atoms. As R 4 to R 7 , a hydrogen atom, an alkyl group having 1 to 10 carbon atoms and a halogen atom are preferable, a hydrogen atom, an alkyl group having 1 to 4 carbon atoms and a halogen atom are more preferable, and a hydrogen atom is particularly preferable. Is.
【００２０】本発明で使用される塩基としては、例え
ば、周期律表ＩもしくはII族金属の水素化物または周期
律表ＩもしくはII族金属のアルコキシドが挙げられる。
周期律表ＩおよびII族金属の水素化物としては、水素化
ナトリウム、水素化カリウム、水素化カルシウム等が挙
げられ、周期律表ＩおよびII族金属のアルコキシドとし
ては、ナトリウムメトキシド、ナトリウムエトキシド、
ナトリウムtert−ブトキシド、カリウムtert−ブトキシ
ド、マグネシウムメトキシド、マグネシウムエトキシド
等が挙げられる。これらの中でも、特にナトリウムおよ
びカリウムの水素化物並びにアルコキシドが好ましい。Examples of the base used in the present invention include a hydride of a metal of Group I or II of the periodic table or an alkoxide of a metal of Group I or II of the periodic table.
Examples of hydrides of metals of groups I and II of the periodic table include sodium hydride, potassium hydride, calcium hydride, and the like, and alkoxides of metals of groups I and II of the periodic table include sodium methoxide and sodium ethoxide. ,
Sodium tert-butoxide, potassium tert-butoxide, magnesium methoxide, magnesium ethoxide and the like can be mentioned. Among these, sodium and potassium hydrides and alkoxides are particularly preferable.
【００２１】塩基として周期律表ＩおよびII族金属のア
ルコキシドを用いた場合には、反応速度および反応収率
の点からアルコールを系外へ除去する操作を行うことが
好ましい。本発明において、上記式（１）で表わされる
エステル類の使用量は、特に制限されるものではない
が、反応収率の点から上記式（２）で表わされるフタル
酸エステルに対し１０〜３００重量％用いるのが好まし
い。また、本発明で使用される塩基の使用量は、上記式
（１）で表わされるエステル類に対し、５０〜５００モ
ル％、好ましくは８０〜３００モル％の範囲とするのが
良い。When an alkoxide of a metal of Group I or II of the Periodic Table is used as a base, it is preferable to remove alcohol from the system from the viewpoint of reaction rate and reaction yield. In the present invention, the amount of the ester represented by the above formula (1) is not particularly limited, but from the viewpoint of reaction yield, it is 10 to 300 relative to the phthalate ester represented by the above formula (2). It is preferred to use weight percent. The amount of the base used in the present invention is in the range of 50 to 500 mol%, preferably 80 to 300 mol% with respect to the ester represented by the above formula (1).
【００２２】本発明の反応は、無溶媒あるいは溶媒で希
釈した状態にて実施される。希釈に使用される溶媒とし
ては、反応に不活性な溶媒であれば特に制限されない
が、ヘキサン、オクタン、ベンゼン、トルエン、キシレ
ン等の炭化水素、ジエチルエーテル、テトラヒドロフラ
ン、ジオキサン、ジブチルエーテル、ジメトキシエタ
ン、ジエトキシエタン等のエーテル系溶媒等が挙げら
れ、特にエーテル系溶媒が反応速度の点から好ましい。
溶媒の使用量は特に制限されるものではないが、フタル
酸エステル誘導体に対し、好ましくは０〜１００倍量
（重量）、より好ましくは２〜３０倍量の範囲で実施さ
れる。本発明の反応温度は、通常０〜３００℃、好まし
くは５０〜２００℃の温度範囲で実施される。上記した
反応で生成する化合物の反応混合物からの分離、精製
は、それ自体既知の通常用いられる方法、例えば、抽
出、再結晶、クロマトグラフィー等により行うことがで
きる。The reaction of the present invention is carried out without solvent or diluted with a solvent. The solvent used for the dilution is not particularly limited as long as it is a solvent inert to the reaction, but is a hydrocarbon such as hexane, octane, benzene, toluene, xylene, diethyl ether, tetrahydrofuran, dioxane, dibutyl ether, dimethoxyethane, Examples thereof include ether solvents such as diethoxyethane, and ether solvents are particularly preferable from the viewpoint of reaction rate.
The amount of the solvent used is not particularly limited, but it is preferably 0 to 100 times (weight), more preferably 2 to 30 times the amount of the phthalate ester derivative. The reaction temperature of the present invention is usually 0 to 300 ° C., preferably 50 to 200 ° C. Separation and purification of the compound produced in the above reaction from the reaction mixture can be carried out by a commonly used method known per se, for example, extraction, recrystallization, chromatography and the like.
【００２３】[0023]
【実施例】以下、本発明を実施例についてさらに詳細に
説明するが、本発明はその要旨を越えない限り、以下の
実施例に限定されるものでない。 実施例１ 水素化ナトリウム１９．２ｇ（水素化ナトリウムを６０
％の分散体として含有する油性試薬）をｎ−ジブチルエ
ーテル２００ｍｌに懸濁させ、加熱還流下、フタル酸ジ
エチル４４．４ｇと酪酸エチル２７．９ｇの混合物を３
０分間かけて滴下し、滴下終了後６時間加熱還流した。
反応液を冷却後、水２００ｍｌを加え、溶解、分液後、
水層をトルエン１００ｍｌで洗浄し、水層に濃塩酸４５
ｍｌを加えて酸性とした。分離してくる油分をトルエン
２００ｍｌで抽出し、有機層を水１００ｍｌで２回洗浄
後、濃縮することにより２−エチル−１，３−インダン
ジオン３０．４ｇ（ガスクロマトグラフィー分析による
純度９５．６％）を得た。その収率は、フタル酸ジエチ
ルに対し８７．３％であった。EXAMPLES The present invention will now be described in more detail with reference to examples, but the present invention is not limited to the following examples as long as the gist thereof is not exceeded. Example 1 19.2 g of sodium hydride (60 g of sodium hydride
% Of the oily reagent contained as a dispersion) in 200 ml of n-dibutyl ether, and under heating and reflux, a mixture of 44.4 g of diethyl phthalate and 27.9 g of ethyl butyrate is mixed with 3 ml.
The mixture was added dropwise over 0 minutes, and heated under reflux for 6 hours after completion of the addition.
After cooling the reaction solution, 200 ml of water was added to dissolve and separate the liquid,
The aqueous layer was washed with 100 ml of toluene, and the aqueous layer was concentrated with concentrated hydrochloric acid 45
It was made acidic by adding ml. The separated oil was extracted with 200 ml of toluene, and the organic layer was washed twice with 100 ml of water and then concentrated to give 30.4 g of 2-ethyl-1,3-indandione (purity 95.6 by gas chromatography analysis. %) Was obtained. The yield was 87.3% with respect to diethyl phthalate.
【００２４】実施例２ カリウムtert−ブトキシド４．３ｇをトルエン１００ｍ
ｌに懸濁させ、２０℃でフタル酸ジエチル７．０ｇと酪
酸エチル５．５ｇの混合物を３０分間かけて滴下し、滴
下終了後、８０℃で３時間反応させた。反応液を冷却
後、水１００ｍｌを加え、溶解、分液後、水層をトルエ
ン５０ｍｌで洗浄し、水層に濃塩酸２５ｍｌを加え酸性
とした。分離してくる油分をトルエン１００ｍｌで抽出
し、有機層を水５０ｍｌで２回洗浄後、濃縮することに
より２−エチル−１，３−インダンジオン３．７ｇ（ガ
スクロマトグラフィー分析による純度９５．０％）を得
た。その収率は、フタル酸ジエチルに対し６４．０％で
あった。Example 2 4.3 g of potassium tert-butoxide was added to 100 m of toluene.
The mixture was suspended in 1, and a mixture of 7.0 g of diethyl phthalate and 5.5 g of ethyl butyrate was added dropwise at 20 ° C. over 30 minutes, and after completion of the dropping, reaction was carried out at 80 ° C. for 3 hours. After cooling the reaction solution, 100 ml of water was added, dissolved and separated, and then the aqueous layer was washed with 50 ml of toluene, and 25 ml of concentrated hydrochloric acid was added to the aqueous layer to make it acidic. The separated oil was extracted with 100 ml of toluene, and the organic layer was washed twice with 50 ml of water and then concentrated to give 3.7 g of 2-ethyl-1,3-indandione (purity 95.0 by gas chromatography analysis: 95.0). %) Was obtained. The yield was 64.0% based on diethyl phthalate.
【００２５】実施例３ 水素化ナトリウム８．４ｇ（水素化ナトリウムを６０％
の分散体として含有する油性試薬）を混合キシレン２０
０ｍｌに懸濁させ、加熱還流下、フタル酸ジエチル２
２．２ｇと酪酸エチル１３．９ｇの混合物を３０分間か
けて滴下し、滴下終了後６時間加熱還流した。反応液を
冷却後、水２００ｍｌを加え溶解、分液後、水層をトル
エン１００ｍｌで洗浄し、水層に濃塩酸２０ｍｌを加え
酸性とした。分離してくる油分をトルエン２００ｍｌで
抽出し、有機層を水１００ｍｌで２回洗浄後、濃縮する
ことにより２−エチル-１，３-インダンジオン１２．９
ｇ（ガスクロマトグラフィー分析による純度９６．０
％）を得た。その収率は、フタル酸ジエチルに対し７
４．２％であった。Example 3 8.4 g of sodium hydride (60% sodium hydride)
Xylene 20 mixed with an oily reagent) contained as a dispersion of
Suspend in 0 ml and heat to reflux with diethyl phthalate 2
A mixture of 2.2 g and ethyl butyrate 13.9 g was added dropwise over 30 minutes, and the mixture was heated under reflux for 6 hours after the completion of the addition. After cooling the reaction solution, 200 ml of water was added to dissolve it, and after liquid separation, the aqueous layer was washed with 100 ml of toluene, and 20 ml of concentrated hydrochloric acid was added to the aqueous layer to make it acidic. The separated oil was extracted with 200 ml of toluene, and the organic layer was washed twice with 100 ml of water and then concentrated to give 2-ethyl-1,3-indandione 12.9.
g (purity 96.0 by gas chromatography analysis
%) Was obtained. The yield is 7 for diethyl phthalate.
4.2%.
【００２６】実施例４ ナトリウムエトキシド１７．０ｇ（ナトリウムエトキシ
ドを６０％の分散体として含有する油性試薬）をジブチ
ルエーテル２００ｍｌに懸濁させ、加熱還流下、フタル
酸ジエチル４４．４ｇと酪酸エチル２５．６ｇの混合物
を３０分間かけて滴下し、滴下終了後６時間加熱還流し
た。この際、副生するエタノールを系外に留出させなが
ら反応を行った。反応液を冷却後、水２００ｍｌを加え
溶解、分液後水層をトルエン１００ｍｌで洗浄し、水層
に濃塩酸４５ｍｌを加え酸性とした。分離してくる油分
をトルエン２００ｍｌで抽出し、有機層を水１００ｍｌ
で２回洗浄後、濃縮することにより２−エチル−１，３
−インダンジオン２９．４ｇ（ガスクロマトグラフィー
分析による純度９５．８％）を得た。その収率は、フタ
ル酸ジエチルに対し８４．３％であった。Example 4 17.0 g of sodium ethoxide (an oily reagent containing 60% of sodium ethoxide as a dispersion) was suspended in 200 ml of dibutyl ether, and 44.4 g of diethyl phthalate and ethyl butyrate were heated and refluxed. 25.6 g of the mixture was added dropwise over 30 minutes, and the mixture was heated under reflux for 6 hours after completion of the addition. At this time, the reaction was carried out while distilling out by-produced ethanol out of the system. After cooling the reaction solution, 200 ml of water was added to dissolve it, and after liquid separation, the aqueous layer was washed with 100 ml of toluene, and 45 ml of concentrated hydrochloric acid was added to the aqueous layer to make it acidic. The separated oil was extracted with 200 ml of toluene, and the organic layer was extracted with 100 ml of water.
2-Ethyl-1,3 by concentrating after washing twice with
-29.4 g of indandione (purity 95.8% by gas chromatography analysis) were obtained. The yield was 84.3% with respect to diethyl phthalate.
【００２７】比較例１ ナトリウム１０．５ｇとフタル酸ジエチル５５．０ｇの
混合物中に、１１５℃で酪酸エチル３０．０ｇを滴下
し、滴下終了後１１５℃で４時間反応させた。反応液を
冷却後、水およびエーテルを加え、分液後、水層に濃硫
酸を加え酸性とした。分離してくる油分をエーテルで抽
出し、濃縮後、蒸留することにより２−エチル−１，３
−インダンジオン１３．７ｇを得た。その収率はフタル
酸ジエチルに対し３２．０％であった。Comparative Example 1 30.0 g of ethyl butyrate was added dropwise at 115 ° C. to a mixture of 10.5 g of sodium and 55.0 g of diethyl phthalate, and after completion of the reaction, reaction was carried out at 115 ° C. for 4 hours. After cooling the reaction solution, water and ether were added, and after liquid separation, concentrated sulfuric acid was added to the aqueous layer to make it acidic. The separated oil is extracted with ether, concentrated and then distilled to give 2-ethyl-1,3.
-13.7 g of indandione were obtained. The yield was 32.0% based on diethyl phthalate.
【００２８】比較例２ 水素化ナトリウム２４．０ｇ（水素化ナトリウムを５０
％の分散体として含有する油性試薬）をベンゼン５００
ｍｌに懸濁させた中に、フタル酸ジメチル１００．０ｇ
と４−ヘプタノン５４．３ｇの混合物を滴下し、滴下終
了後１５時間加熱還流した。反応液を冷却後、水７５０
ｍｌを加え溶解、分液後、水層をトルエン５０ｍｌで洗
浄し、水層に濃塩酸２５ｍｌを加え酸性とした。分離し
てくる油分ををトルエン１００ｍｌで抽出し、濃縮後、
アルミナカラムクロマトグラフィーで精製することによ
り２−エチル−１，３−インダンジオン４８．４ｇを得
た。その収率はフタル酸ジメチルに対し５４．０％であ
った。Comparative Example 2 Sodium hydride 24.0 g (sodium hydride 50
% Of oily reagent) contained as a dispersion of benzene 500
100.0 g of dimethyl phthalate while suspended in ml
And 4-heptanone (54.3 g) were added dropwise, and the mixture was heated under reflux for 15 hours after completion of the addition. After cooling the reaction solution, water 750
After addition of ml, dissolution and liquid separation, the aqueous layer was washed with 50 ml of toluene, and 25 ml of concentrated hydrochloric acid was added to the aqueous layer to make it acidic. The separated oil is extracted with 100 ml of toluene, and after concentration,
Purification by alumina column chromatography gave 48.4 g of 2-ethyl-1,3-indandione. The yield was 54.0% with respect to dimethyl phthalate.
【００２９】[0029]
【発明の効果】本発明によれば、医薬および農薬の中間
体として有用な２置換−１，３−インダンジオンを高収
率で容易に得ることができ、その工業的価値は高い。INDUSTRIAL APPLICABILITY According to the present invention, 2-substituted-1,3-indandione useful as an intermediate for medicines and agricultural chemicals can be easily obtained in high yield, and its industrial value is high.
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.6 識別記号 庁内整理番号 ＦＩ 技術表示箇所 Ｃ０７Ｃ 49/697 Ｃ０７Ｃ 49/697 // Ｃ０７Ｂ 61/00 ３００ Ｃ０７Ｂ 61/00 ３００ ─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. 6 Identification number Office reference number FI technical display location C07C 49/697 C07C 49/697 // C07B 61/00 300 C07B 61/00 300
Claims (4)
数２〜１０のアルケニル基または炭素数２〜１０のアル
キニル基を表し、Ｒ2 は炭素数１〜４のアルキル基を表
す）で表されるエステル類と、下記一般式（２） 【化２】 （上記式中、Ｒ3 は炭素数１〜４のアルキル基を表し、
Ｒ4 、Ｒ5 、Ｒ6 およびＲ7 はそれぞれ独立して、水素
原子、炭素数１〜１０のアルキル基、炭素数２〜１０の
アルケニル基、炭素数２〜１０のアルキニル基、炭素数
１〜１０のアルコキシル基またはハロゲン原子を表す）
で表されるフタル酸エステル誘導体とを塩基の存在下、
反応させることを特徴とする、下記一般式（３） 【化３】 （上記式中、Ｒ1 は炭素数１〜１０のアルキル基、炭素
数２〜１０のアルケニル基、炭素数２〜１０のアルキニ
ル基を表し、Ｒ4 、Ｒ5 、Ｒ6 およびＲ7 はそれぞれ独
立して、水素原子、炭素数１〜１０のアルキル基、炭素
数２〜１０のアルケニル基、炭素数２〜１０のアルキニ
ル基、炭素数１〜１０のアルコキシル基またはハロゲン
原子を表す）で表される２置換−１，３−インダンジオ
ン誘導体の製造法。1. A compound represented by the following general formula (1): embedded image R 1 CH 2 CO 2 R 2 (1) (wherein R 1 is an alkyl group having 1 to 10 carbon atoms, an alkenyl having 2 to 10 carbon atoms). Group or an alkynyl group having 2 to 10 carbon atoms, and R 2 represents an alkyl group having 1 to 4 carbon atoms), and an ester represented by the following general formula (2): (In the above formula, R 3 represents an alkyl group having 1 to 4 carbon atoms,
R 4 , R 5 , R 6 and R 7 are each independently a hydrogen atom, an alkyl group having 1 to 10 carbon atoms, an alkenyl group having 2 to 10 carbon atoms, an alkynyl group having 2 to 10 carbon atoms, and 1 carbon atom. 10 represents an alkoxyl group or a halogen atom)
In the presence of a phthalate derivative represented by
The following general formula (3) is characterized in that the reaction is carried out. (In the above formula, R 1 represents an alkyl group having 1 to 10 carbon atoms, an alkenyl group having 2 to 10 carbon atoms, an alkynyl group having 2 to 10 carbon atoms, and R 4 , R 5 , R 6 and R 7 are respectively Independently represent a hydrogen atom, an alkyl group having 1 to 10 carbon atoms, an alkenyl group having 2 to 10 carbon atoms, an alkynyl group having 2 to 10 carbon atoms, an alkoxyl group having 1 to 10 carbon atoms or a halogen atom). Of the substituted 2-substituted-1,3-indandione derivative.
し、Ｒ2 は炭素数１〜４のアルキル基を表す）で表され
るエステル類と、下記一般式（５） 【化５】 （上記式中、Ｒ3 は炭素数１〜４のアルキル基を表す）
で表されるフタル酸エステルとを塩基の存在下、反応さ
せることを特徴とする、下記一般式（６） 【化６】 （上記式中、Ｒ1'は炭素数１〜１０のアルキル基を表
す）で表される２置換−１，３-インダンジオン誘導体
の製造法。2. A compound represented by the following general formula (4): embedded image R 1 ′ CH 2 CO 2 R 2 (4) (wherein R 1 ′ represents an alkyl group having 1 to 10 carbon atoms, and R 2 is An ester represented by a C1-4 alkyl group) and a compound represented by the following general formula (5): (In the above formula, R 3 represents an alkyl group having 1 to 4 carbon atoms)
A phthalic acid ester represented by the following formula in the presence of a base, characterized by the following general formula (6): (In the above formula, R 1 ′ represents an alkyl group having 1 to 10 carbon atoms) and a method for producing a 2-substituted-1,3-indandione derivative.
の水素化物を用いることを特徴とする請求項１または２
記載の製造法。3. A hydride of a metal of Group I or II of the periodic table is used as the base.
Production method as described.
のアルコキシドを用いることを特徴とする請求項１また
は２記載の製造法。4. The method according to claim 1, wherein an alkoxide of a metal of Group I or II of the periodic table is used as the base.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP17490595A JP3513726B2 (en) | 1995-07-11 | 1995-07-11 | Method for producing disubstituted-1,3-indandione derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP17490595A JP3513726B2 (en) | 1995-07-11 | 1995-07-11 | Method for producing disubstituted-1,3-indandione derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH0920715A true JPH0920715A (en) | 1997-01-21 |
| JP3513726B2 JP3513726B2 (en) | 2004-03-31 |
Family
ID=15986758
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP17490595A Expired - Fee Related JP3513726B2 (en) | 1995-07-11 | 1995-07-11 | Method for producing disubstituted-1,3-indandione derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3513726B2 (en) |
-
1995
- 1995-07-11 JP JP17490595A patent/JP3513726B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JP3513726B2 (en) | 2004-03-31 |
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