JPH05286894A - New production of carboxylic acid ester or carboxylic acid thioster - Google Patents
New production of carboxylic acid ester or carboxylic acid thiosterInfo
- Publication number
- JPH05286894A JPH05286894A JP4175792A JP17579292A JPH05286894A JP H05286894 A JPH05286894 A JP H05286894A JP 4175792 A JP4175792 A JP 4175792A JP 17579292 A JP17579292 A JP 17579292A JP H05286894 A JPH05286894 A JP H05286894A
- Authority
- JP
- Japan
- Prior art keywords
- carboxylic acid
- ester
- general formula
- formula
- acid ester
- 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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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】本発明はカルボン酸エステル又は
カルボン酸チオエステルの新規な製造方法に関する。TECHNICAL FIELD The present invention relates to a novel method for producing a carboxylic acid ester or a carboxylic acid thioester.
【０００２】[0002]
【従来の技術】種々の生理活性物質にはエステル残基又
はチオエステル残基を含む化合物が数多く知られてお
り、エステル又はチオエステル合成反応は、有機合成上
極めて重要な反応である。2. Description of the Related Art Many compounds containing an ester residue or a thioester residue are known as various physiologically active substances, and the ester or thioester synthesis reaction is a very important reaction in organic synthesis.
【０００３】従来、対応するカルボン酸とアルコール又
はチオールから、カルボン酸エステル又はカルボン酸チ
オエステルを合成する方法としては以下に示す方法が一
般的である。Conventionally, as a method for synthesizing a carboxylic acid ester or a carboxylic acid thioester from a corresponding carboxylic acid and an alcohol or a thiol, the following method is generally used.
【０００４】即ち、（１）カルボン酸とアルコール又は
チオールとを、触媒量のプロトン酸又はルイス酸存在下
に加熱する方法、或いは、（２）当量以上のプロトン酸
又はルイス酸を用いる方法、並びに（３）塩基性条件下
でカルボン酸の活性誘導体とアルコール又はチオールか
ら合成する方法等である。That is, (1) a method of heating a carboxylic acid and an alcohol or a thiol in the presence of a catalytic amount of a protonic acid or a Lewis acid, or (2) a method of using an equivalent amount or more of a protonic acid or a Lewis acid, (3) A method of synthesizing an active derivative of a carboxylic acid and an alcohol or a thiol under basic conditions.
【０００５】しかし、種々の生理活性物質においては、
近年、ますます複雑な構造を持つ不安定な化合物が合成
目標として取り上げられることが多く、より中性に近い
温和な条件下で、しかも当量のカルボン酸とアルコール
又はチオールから円滑に進行するエステル又はチオエス
テル合成法が医薬品合成上からも望まれている。However, in various physiologically active substances,
In recent years, unstable compounds having an increasingly complex structure are often taken up as a synthetic target, and the ester or the ester which smoothly proceeds from a moderate amount of carboxylic acid and alcohol or thiol under mild conditions close to neutrality. The thioester synthesis method is also desired from the viewpoint of drug synthesis.
【０００６】当量のカルボン酸とアルコール又はチオー
ルから、エステル又はチオエステルを得る簡便な合成法
に関する知見は未だ数少なく、例えば、１−アルキル−
２−ハロピリジニウム塩によるエステル化反応(T.Mukai
yama,Angew.Chem.,Int.ED.Engl,18,707(1979))及び2,4,
6−トリクロロベンゾイルクロリドを用い、塩基性条件
下、混合酸無水物を経由する方法(K.Hirata,H.Saeki,T.
Katsuki,and M.Yamaguchi,Bull.Chem.Soc.Japan.,52,19
89(1979))が挙げられる。しかし、これらの方法では、
不飽和エステル類を、異性化を伴うことなく純粋に得る
ことが困難なことも知られている。エステル又はチオエ
ステルを得る簡便な合成法の開発は、有機合成上未だ残
された大きな課題である。There are still few findings on a simple synthetic method for obtaining an ester or thioester from an equivalent amount of carboxylic acid and alcohol or thiol, for example, 1-alkyl-
Esterification reaction with 2-halopyridinium salt (T. Mukai
yama, Angew.Chem., Int.ED.Engl, 18,707 (1979)) and 2,4,
Using 6-trichlorobenzoyl chloride, under basic conditions, via a mixed acid anhydride (K. Hirata, H. Saeki, T.
Katsuki, and M.Yamaguchi, Bull.Chem.Soc.Japan., 52,19
89 (1979)). But with these methods,
It is also known that it is difficult to obtain unsaturated esters purely without isomerization. Development of a simple synthetic method for obtaining an ester or a thioester is a major problem that remains in organic synthesis.
【０００７】[0007]
【発明が解決しようとする問題点】本発明の目的は、ア
ルコール又はチオールと、当量もしくは小過剰のカルボ
ン酸から、温和な条件下で、効率的にカルボン酸エステ
ル又はカルボン酸チオエステルを製造する方法を提供す
ることにある。DISCLOSURE OF THE INVENTION An object of the present invention is to efficiently produce a carboxylic acid ester or a carboxylic acid thioester from alcohol or thiol and an equivalent or small excess of carboxylic acid under mild conditions. To provide.
【０００８】[0008]
【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研究を重ねた結果、アルコール又
はチオール又はそのシリル誘導体と、当量もしくは小過
剰のカルボン酸又はそのシリルエステル誘導体を反応さ
せ、カルボン酸エステル又はカルボン酸チオエステルを
製造する際に、一般式（３） （Ｒ6ＣＯ）2Ｏ （３） （式中、Ｒ6は置換基を有していてもよいアリール基を
示す）で表されるカルボン酸無水物と触媒量のカチオン
性触媒を共存させることにより、温和な条件下で、効率
的にカルボン酸エステル又はカルボン酸チオエステルを
製造できることを見出し、発明を完成した。Means for Solving the Problems As a result of intensive studies to solve the above problems, the present inventors have found that alcohol or thiol or its silyl derivative and an equivalent or small excess of carboxylic acid or its silyl ester derivative. In the production of a carboxylic acid ester or a carboxylic acid thioester, the compound represented by the general formula (3) (R 6 CO) 2 O (3) (in the formula, R 6 is an aryl group which may have a substituent) The present invention has been completed and found that a carboxylic acid ester or a carboxylic acid thioester can be efficiently produced under mild conditions by coexisting a carboxylic acid anhydride represented by ..
【０００９】したがって、本発明は、一般式（１） Ｒ1ＣＯＯＺ （１） （式中、Ｒ1は置換基を有していてもよいアルキル基又
はアリール基を、Ｚは水素又はＳｉ（Ｒ2）（Ｒ3）（Ｒ
4）を示し、Ｒ2、Ｒ3、Ｒ4は同一又は相異なる低級アル
キル基を示す）で表されるカルボン酸又はカルボン酸シ
リルエステル誘導体と、一般式（２） Ｒ5ＸＺ （２） （式中、Ｒ5は置換基を有していてもよいアルキル基又
はアリール基を、Ｘは酸素原子又は硫黄原子を示し、Ｚ
は前記と同一）で表されるアルコール又はチオール、或
いはそのシリル誘導体とを反応させる工程において、一
般式（３） （Ｒ6ＣＯ）2Ｏ （３） （式中、Ｒ6は置換基を有していてもよいアリール基を
示す）で表されるカルボン酸無水物と触媒量のカチオン
性触媒を共存させることを特徴とするカルボン酸エステ
ル又はカルボン酸チオエステルの製造方法に関する。Accordingly, the present invention has the general formula (1) R 1 COOZ (1 ) ( wherein, R 1 represents an alkyl group or an aryl group which may have a substituent group, Z is hydrogen or Si (R 2 ) (R 3 ) (R
4 ), wherein R 2 , R 3 and R 4 represent the same or different lower alkyl groups) and a carboxylic acid or carboxylic acid silyl ester derivative represented by the general formula (2) R 5 XZ (2) ( In the formula, R 5 is an optionally substituted alkyl group or aryl group, X is an oxygen atom or a sulfur atom, and Z is
In the step of reacting with an alcohol or a thiol represented by the above) or a silyl derivative thereof, in the general formula (3) (R 6 CO) 2 O (3) (in the formula, R 6 has a substituent). (Which represents an optionally substituted aryl group), and a catalytic amount of a cationic catalyst are allowed to coexist together with a carboxylic acid ester or a carboxylic acid thioester.
【００１０】即ち、触媒量のカチオン性触媒の存在下
に、一般式（１） Ｒ1ＣＯＯＺ （１） （式中、Ｚは前記と同一）で表されるカルボン酸又はカ
ルボン酸シリルエステル誘導体と一般式（３） （Ｒ6ＣＯ）2Ｏ （３） （式中、Ｒ6は前記と同一）で表されるカルボン酸無水
物とを、アセトニトリル、エーテル、１，２−ジクロル
エタン、ベンゼン、トルエン、ジクロルメタン等の反応
に関与しない溶媒中、０〜５０℃、好ましくは１０〜３
０℃で反応させ、次いで一般式（２） Ｒ5ＸＺ （２） （式中、Ｒ5，Ｘ，Ｚ，は前記と同一）で表されるアル
コール又はチオール、或いはそのシリル誘導体とを反応
させることにより対応するカルボン酸エステル又はカル
ボン酸チオエステル（４） Ｒ1ＣＯＸＲ5 （４） （式中、Ｘ，Ｒ1、Ｒ5は前記と同一）を高収率で得るこ
とができる。That is, in the presence of a catalytic amount of a cationic catalyst, a carboxylic acid or a carboxylic acid silyl ester derivative represented by the general formula (1) R 1 COOZ (1) (wherein Z is the same as above) A carboxylic acid anhydride represented by the general formula (3) (R 6 CO) 2 O (3) (wherein R 6 is the same as the above) is treated with acetonitrile, ether, 1,2-dichloroethane, benzene, and toluene. , In a solvent that does not participate in the reaction such as dichloromethane, 0 to 50 ° C., preferably 10 to 3
The reaction is carried out at 0 ° C., and then an alcohol or thiol represented by the general formula (2) R 5 XZ (2) (wherein R 5 , X, Z, are the same as described above) or a silyl derivative thereof is reacted. As a result, the corresponding carboxylic acid ester or carboxylic acid thioester (4) R 1 COXR 5 (4) (in the formula, X, R 1 and R 5 are the same as above) can be obtained in high yield.
【００１１】ここで、一般式（１）中のＲ1並びに一般
式（２）中のＲ5は基本的にはいかなる置換基でもよ
く、一般にエステル化反応が困難とされている置換基を
有するものでも本発明方法によればエステル化が可能で
ある。Here, R 1 in the general formula (1) and R 5 in the general formula (2) may be basically any substituents, and generally have a substituent that is difficult to esterify. Esterification is possible even by using the method of the present invention.
【００１２】一般式（１）及び一般式（２）においてＺ
は水素であることも可能だが、Ｚが置換シリル基である
場合が好ましく、Ｒ2、Ｒ3、Ｒ4は、炭素数１〜６の低
級アルキル基で、例えばメチル基、エチル基、ｔ−ブチ
ル基等が好ましい。Z in the general formulas (1) and (2)
May be hydrogen, but it is preferable that Z is a substituted silyl group, and R 2 , R 3 and R 4 are lower alkyl groups having 1 to 6 carbon atoms, for example, methyl group, ethyl group, t- Butyl group and the like are preferable.
【００１３】また、一般式（３）のＲ6は、電子吸引性
基を有するアリール基が好ましく、特にフッ素原子、塩
素原子等のハロゲン原子、トリクロルメチル基、トリフ
ルオロメチル基等のハロゲン置換低級アルキル基等で置
換されたフェニル基が好ましい。Further, R 6 in the general formula (3) is preferably an aryl group having an electron-withdrawing group, particularly a halogen atom such as a fluorine atom and a chlorine atom, a halogen-substituted lower group such as a trichloromethyl group and a trifluoromethyl group. A phenyl group substituted with an alkyl group or the like is preferable.
【００１４】また、カチオン性触媒とは、四塩化チタ
ン、塩化ハフニウム、塩化ジルコニウム、塩化アルミニ
ウム、塩化ガリウム、塩化インジウム、塩化鉄、塩化ス
ズ (II)等の各種ルイス酸、又は過塩素酸銀、トリフル
オロメタンスルホン酸銀等の銀塩と各種ルイス酸との複
合塩、及びトリフルオロメタンスルホン酸スズ(II)等が
好ましく、基質である一般式（１）の化合物に対しての
０．０１〜１００モル％使用することが好ましい。０．
０１モル％以下では充分な触媒効果が得られず、１００
モル％以上加えても触媒効果に変わりはなく、製造コス
トが嵩むだけである。The cationic catalyst means various Lewis acids such as titanium tetrachloride, hafnium chloride, zirconium chloride, aluminum chloride, gallium chloride, indium chloride, iron chloride and tin (II) chloride, or silver perchlorate, A complex salt of a silver salt such as silver trifluoromethanesulfonate and various Lewis acids, tin (II) trifluoromethanesulfonate, and the like are preferable, and 0.01 to 100 relative to the compound of the general formula (1) which is a substrate. It is preferable to use mol%. 0.
If it is less than 01 mol%, a sufficient catalytic effect cannot be obtained,
Addition of more than mol% does not change the catalytic effect, but only increases the manufacturing cost.
【００１５】本発明方法によれば、通常の混合酸無水物
を用いたエステル化反応で副生する不純物（上記一般式
で言えば、一般式（２）で表される化合物と一般式
（３）で表される化合物が反応したもの）はまったく得
られず、高い化学選択性を示す。一般式（１）及び一般
式（２）でＺが置換シリル基である化合物は、対応する
カルボン酸並びにアルコール又はチオールより通常良く
知られた方法により製造することができ、得られたシリ
ル化合物は単離する事なく、本発明方法に使用すること
ができる。According to the method of the present invention, impurities by-produced in the esterification reaction using a usual mixed acid anhydride (in the above general formula, the compound represented by the general formula (2) and the general formula (3) The compound represented by) is not obtained at all and shows high chemoselectivity. The compounds of the general formula (1) and the general formula (2) in which Z is a substituted silyl group can be prepared from the corresponding carboxylic acid and alcohol or thiol by a generally known method. It can be used in the method of the present invention without isolation.
【００１６】[0016]
【実施例】以下に実施例を示し、本発明方法の有用性を
示すが、本発明は実施例に限定されるものではない。EXAMPLES The usefulness of the method of the present invention is shown below, but the present invention is not limited to the examples.
【００１７】実施例１ Example 1
【００１８】[0018]
【化１】 [Chemical 1]
【００１９】アルゴン気流下、トリフルオロメタンスル
ホン酸銀（９．９ｍｇ，０．０３８５ｍＭ）を２ｍｌの
ジクロルメタンに懸濁させ、室温にて四塩化チタンのト
ルエン溶液０．０３８５ｍｌ（０．５モル濃度、０．０
１９３ｍＭ）を加え、同温度で０．５時間撹拌した。こ
れにジクロルメタン１．５ｍｌに溶解した３−フェニル
プロピオン酸トリメチルシリルエステル（４５．６ｍ
ｇ、０．２０５ｍＭ）及び４−トリフルオロメチル安息
香酸無水物（７０．０ｍｇ、０．１９３ｍＭ）の混液を
加えた。次いで、ジクロルメタン０．５ｍｌに溶解した
４−フェニル−２−ブタントリメチルシリルエーテル
（４４．６ｍｇ、０．２０１ｍＭ）を加えて、同温度で
３時間撹拌した。反応液にｐＨ７のリン酸緩衝液を加え
た後、ジクロルメタンで抽出した。有機層を無水硫酸ナ
トリウムで乾燥後、濾液を減圧濃縮した。残渣をシリカ
ゲル薄層クロマトグラフィー（展開溶媒ヘキサン：酢酸
エチル＝９：１）にて精製し、目的物（５０．３ｍｇ、
収率９２％）を得た。ＮＭＲ（ＣＤＣｌ3、ＴＭＳ標
準） δＰＰＭ：７．３１〜７．１１（１０Ｈ，ｍ）、
４．９９〜４．８８（１Ｈ，ｍ）、２．９５（２Ｈ，
ｔ，Ｊ＝７．９Ｈｚ）、２．６６〜２．５１（４Ｈ，
ｍ）、１．９６〜１．７２（２Ｈ，ｍ）、１．２１（３
Ｈ，ｄ，Ｊ＝６．３Ｈｚ）。Under a stream of argon, silver trifluoromethanesulfonate (9.9 mg, 0.0385 mM) was suspended in 2 ml of dichloromethane, and at room temperature, 0.0385 ml of a toluene solution of titanium tetrachloride (0.5 molar concentration, 0 .0
193 mM) was added, and the mixture was stirred at the same temperature for 0.5 hr. 3-phenylpropionic acid trimethylsilyl ester dissolved in 1.5 ml of dichloromethane (45.6 m)
g, 0.205 mM) and 4-trifluoromethylbenzoic anhydride (70.0 mg, 0.193 mM). Then, 4-phenyl-2-butanetrimethylsilyl ether (44.6 mg, 0.201 mM) dissolved in 0.5 ml of dichloromethane was added, and the mixture was stirred at the same temperature for 3 hours. After adding a pH 7 phosphate buffer to the reaction solution, the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel thin layer chromatography (developing solvent hexane: ethyl acetate = 9: 1) to obtain the desired product (50.3 mg,
Yield 92%) was obtained. NMR (CDCl 3 , TMS standard) δPPM: 7.31 to 7.11 (10H, m),
4.99-4.88 (1H, m), 2.95 (2H, m)
t, J = 7.9 Hz), 2.66 to 2.51 (4H,
m), 1.96 to 1.72 (2H, m), 1.21 (3
H, d, J = 6.3 Hz).
【００２０】実施例２〜５ 実施例１に準じて、一般式（３）で表されるカルボン酸
無水物を変更して反応を実施した。結果を表１に示す。 Examples 2 to 5 According to Example 1, the reaction was carried out by changing the carboxylic acid anhydride represented by the general formula (3). The results are shown in Table 1.
【００２１】[0021]
【化２】 [Chemical 2]
【００２２】[0022]
【表１】 [Table 1]
【００２３】実施例６〜１４ 実施例１に準じて、カチオン性触媒を変更して反応を実
施した。結果を表２に示す。 Examples 6 to 14 In accordance with Example 1, the reaction was carried out by changing the cationic catalyst. The results are shown in Table 2.
【００２４】[0024]
【化３】 [Chemical 3]
【００２５】[0025]
【表２】 [Table 2]
【００２６】実施例１５〜２５ 実施例１に準じて、カルボン酸シリルエステル誘導体及
びシリルエーテル誘導体、並びにカチオン性触媒を変更
して反応を実施した。結果を表３に示す。 Examples 15 to 25 According to Example 1, the reaction was carried out by changing the carboxylic acid silyl ester derivative and the silyl ether derivative and the cationic catalyst. The results are shown in Table 3.
【００２７】[0027]
【化４】 [Chemical 4]
【００２８】[0028]
【表３】 [Table 3]
【００２９】実施例２６ Example 26
【００３０】[0030]
【化５】 [Chemical 5]
【００３１】アルゴン気流下、過塩素酸銀２０．５ｍｇ
を２ｍｌのジクロルメタンに懸濁させ、室温にて四塩化
チタンのトルエン溶液０．０９９ｍｌ（０．５モル濃
度）を加え、更に乾燥したモレキュラシーブス３Ａ５０
ｍｇを加え０．５時間撹拌した。これにジクロルメタン
１ｍｇに溶解した酢酸１５．９ｍｇ及び４−トリフルオ
ルメチル安息香酸無水物８９．８ｍｇの混液を加えた。
次いで、ジクロルメタン０．５ｍｌに溶解した４−フェ
ニル−２−ブタノール３７．２ｍｇを加えて、同温度で
３時間撹拌した。反応液に飽和重曹水を加えた後、ジク
ロルメタンで抽出した。有機層を無水硫酸ナトリウムで
乾燥後、濾液を減圧濃縮した。残渣をシリカゲル薄層ク
ロマトグラフィー（展開溶媒ヘキサン：酢酸エチル＝
９：１）にて精製し、目的物３９．９ｍｇ（収率８４
％）を得た。ＮＭＲ（ＣＤＣｌ3，ＴＭＳ標準） δＰ
ＰＭ：７．３１〜７．１５（５Ｈ，ｍ）、４．９７〜
４．９０（１Ｈ，ｍ）、２．７３〜２．５３（２Ｈ，
ｍ）、２．０３（３Ｈ，ｓ）、１．９９〜１．７６（２
Ｈ，ｍ）、１．２５（３Ｈ，ｄ，Ｊ＝６．３Ｈｚ）。20.5 mg of silver perchlorate under a stream of argon
Was suspended in 2 ml of dichloromethane, 0.099 ml (0.5 molar concentration) of a toluene solution of titanium tetrachloride was added at room temperature, and further dried Molecular Sieves 3A50.
mg was added and the mixture was stirred for 0.5 hours. A mixed solution of 15.9 mg of acetic acid and 89.8 mg of 4-trifluoromethylbenzoic anhydride dissolved in 1 mg of dichloromethane was added thereto.
Next, 37.2 mg of 4-phenyl-2-butanol dissolved in 0.5 ml of dichloromethane was added, and the mixture was stirred at the same temperature for 3 hours. Saturated aqueous sodium hydrogen carbonate was added to the reaction solution, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate, and the filtrate was concentrated under reduced pressure. The residue was subjected to silica gel thin layer chromatography (developing solvent hexane: ethyl acetate =
9: 1) to obtain 39.9 mg of the desired product (yield 84
%) Was obtained. NMR (CDCl 3 , TMS standard) δP
PM: 7.31 to 7.15 (5H, m), 4.97 to
4.90 (1H, m), 2.73 to 2.53 (2H,
m), 2.03 (3H, s), 1.99 to 1.76 (2
H, m), 1.25 (3H, d, J = 6.3 Hz).
【００３２】実施例２７ Example 27
【００３３】[0033]
【化６】 [Chemical 6]
【００３４】アルゴン気流下、トリフルオロメタンスル
ホン酸スズ（ＩＩ）２０．４ｍｇを２ｍｌのジクロルメ
タンに加え、室温で０．５時間撹拌した。これにジクロ
ルメタン１ｍｌに溶解したクロトン酸トリメチルシリル
エステル３９．５ｍｇ及び４−トリフルオロメチル安息
香酸無水物８８．６ｍｇの混液を加えた。次いで、ジク
ロルメタン０．５ｍｌに溶解した３−フェニル−１−プ
ロパントリメチルシリルエーテル５２．４ｍｇを加え
て、同温度で３時間撹拌した。反応液に飽和重曹水を加
えた後、ジクロルメタンで抽出した。有機層を無水硫酸
ナトリウムで乾燥後、濾液を減圧濃縮した。残渣をシリ
カゲル薄層クロマトグラフィー（展開溶媒ヘキサン：酢
酸エチル＝９：１）にて精製し、目的物４６．８ｍｇ
（収率９４％）を得た。ＮＭＲ（ＣＤＣｌ3，ＴＭＳ標
準） δＰＰＭ：７．２７〜６．９２（５Ｈ，ｍ）、
５．８８（１Ｈ，ｄ，Ｊ＝１．７Ｈｚ）、５．８２（１
Ｈ，ｄ，Ｊ＝１．７Ｈｚ）、４．１４（２Ｈ，ｔ，Ｊ＝
６．６Ｈｚ）、２．７０（２Ｈ，ｔ，Ｊ＝７．２Ｈ
ｚ）、２．０３〜１．９６（２Ｈ，ｍ）、１．８７（３
Ｈ，ｄｄ，Ｊ＝６．９Ｈｚ，１．７Ｈｚ）。Under an argon stream, 20.4 mg of tin (II) trifluoromethanesulfonate was added to 2 ml of dichloromethane, and the mixture was stirred at room temperature for 0.5 hours. A mixed solution of 39.5 mg of crotonic acid trimethylsilyl ester and 88.6 mg of 4-trifluoromethylbenzoic anhydride dissolved in 1 ml of dichloromethane was added thereto. Then, 52.4 mg of 3-phenyl-1-propanetrimethylsilyl ether dissolved in 0.5 ml of dichloromethane was added, and the mixture was stirred at the same temperature for 3 hours. Saturated aqueous sodium hydrogen carbonate was added to the reaction solution, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel thin layer chromatography (developing solvent hexane: ethyl acetate = 9: 1) to obtain 46.8 mg of the desired product.
(Yield 94%) was obtained. NMR (CDCl 3 , TMS standard) δPPM: 7.27 to 6.92 (5H, m),
5.88 (1H, d, J = 1.7Hz), 5.82 (1
H, d, J = 1.7 Hz), 4.14 (2H, t, J =
6.6 Hz), 2.70 (2H, t, J = 7.2H
z), 2.03 to 1.96 (2H, m), 1.87 (3
H, dd, J = 6.9 Hz, 1.7 Hz).
【００３５】実施例２８ Example 28
【００３６】[0036]
【化７】 [Chemical 7]
【００３７】アルゴン気流下、トリフルオロメタンスル
ホン酸銀（７．３ｍｇ，０．０２８４ｍＭ）を２ｍｌの
ジクロルメタンに懸濁させ、室温にて四塩化チタンのト
ルエン溶液０．０２８４ｍｌ（０．５モル濃度、０．０
１４２ｍＭ）を加え、同温度で０．５時間撹拌した。こ
れにジクロルメタン１．５ｍｌに溶解した３−フェニル
プロピオン酸トリメチルシリルエステル（３５．８ｍ
ｇ、０．１６１ｍＭ）及び４−トリフルオロメチル安息
香酸無水物（５６．５ｍｇ、０．１５６ｍＭ）の混液を
加えた。次いで、ジクロルメタン０．５ｍｌに溶解した
フェニルチオトリメチルシラン（２５．７ｍｇ、０．１
４１ｍＭ）を加えて、同温度で３時間撹拌した。反応液
にｐＨ７のリン酸緩衝液を加えた後、ジクロルメタンで
抽出した。有機層を無水硫酸ナトリウムで乾燥後、濾液
を減圧濃縮した。残渣をシリカゲル薄層クロマトグラフ
ィー（展開溶媒ヘキサン：酢酸エチル＝９：１）にて精
製し、目的物（３１．５ｍｇ、収率９２％）を得た。Ｎ
ＭＲ（ＣＤＣｌ3、ＴＭＳ標準） δＰＰＭ：７．３９
〜７．１９（１０Ｈ，ｍ）、３．０４〜２．９２（４
Ｈ，ｍ）。Under a stream of argon, silver trifluoromethanesulfonate (7.3 mg, 0.0284 mM) was suspended in 2 ml of dichloromethane, and at room temperature, 0.0284 ml of a toluene solution of titanium tetrachloride (0.5 molar concentration, 0 .0
(142 mM) was added, and the mixture was stirred at the same temperature for 0.5 hr. 3-phenylpropionic acid trimethylsilyl ester (35.8 m) dissolved in 1.5 ml of dichloromethane.
g, 0.161 mM) and 4-trifluoromethylbenzoic anhydride (56.5 mg, 0.156 mM). Then, phenylthiotrimethylsilane (25.7 mg, 0.1%) dissolved in 0.5 ml of dichloromethane.
41 mM) was added and the mixture was stirred at the same temperature for 3 hours. After adding a pH 7 phosphate buffer to the reaction solution, the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel thin layer chromatography (developing solvent hexane: ethyl acetate = 9: 1) to obtain the desired product (31.5 mg, yield 92%). N
MR (CDCl 3 , TMS standard) δPPM: 7.39
~ 7.19 (10H, m), 3.04 to 2.92 (4
H, m).
【００３８】実施例２９〜４２ 実施例２８に準じて、カルボン酸シリルエステル誘導体
及びシリルチオエーテル誘導体を変更して反応を実施し
た。結果を表４に示す。Examples 29 to 42 According to Example 28, the reaction was carried out by changing the carboxylic acid silyl ester derivative and the silyl thioether derivative. The results are shown in Table 4.
【００３９】[0039]
【化８】 [Chemical 8]
【００４０】[0040]
【表４】 [Table 4]
【００４１】[0041]
【発明の効果】以上のように、本発明方法によればアル
コール又はチオールとカルボン酸から、温和な条件下
で、高収率でカルボン酸エステル又はカルボン酸チオエ
ステルを製造することが可能である。As described above, according to the method of the present invention, it is possible to produce a carboxylic acid ester or a carboxylic acid thioester from alcohol or thiol and carboxylic acid in a high yield under mild conditions.
Claims (3)
はアリール基を、Ｚは水素又はＳｉ（Ｒ2）（Ｒ3）（Ｒ
4）を示し、Ｒ2、Ｒ3、Ｒ4は同一又は相異なる低級アル
キル基を示す）で表されるカルボン酸又はカルボン酸シ
リルエステル誘導体と、一般式（２） Ｒ5ＸＺ （２） （式中、Ｒ5は置換基を有していてもよいアルキル基又
はアリール基を、Ｘは酸素原子又は硫黄原子を示し、Ｚ
は前記と同一）で表されるアルコール又はチオール、或
いはそのシリル誘導体とを反応させる工程において、一
般式（３） （Ｒ6ＣＯ）2Ｏ （３） （式中、Ｒ6は置換基を有していてもよいアリール基を
示す）で表されるカルボン酸無水物と触媒量のカチオン
性触媒を共存させることを特徴とするカルボン酸エステ
ル又はカルボン酸チオエステルの製造方法。1. A compound represented by the general formula (1) R 1 COOZ (1) (wherein, R 1 is an alkyl group or aryl group which may have a substituent, Z is hydrogen or Si (R 2 ) (R 3 ) (R
4 ), wherein R 2 , R 3 and R 4 represent the same or different lower alkyl groups) and a carboxylic acid or carboxylic acid silyl ester derivative represented by the general formula (2) R 5 XZ (2) ( In the formula, R 5 is an optionally substituted alkyl group or aryl group, X is an oxygen atom or a sulfur atom, and Z is
In the step of reacting with an alcohol or a thiol represented by the above) or a silyl derivative thereof, in the general formula (3) (R 6 CO) 2 O (3) (in the formula, R 6 has a substituent). Which represents an optionally substituted aryl group) and a catalytic amount of a cationic catalyst are allowed to coexist, and a method for producing a carboxylic acid ester or a carboxylic acid thioester.
ロフェニル基である請求項１記載のカルボン酸エステル
又はカルボン酸チオエステルの製造方法。2. The method for producing a carboxylic acid ester or a carboxylic acid thioester according to claim 1, wherein R 6 in the general formula (3) is a 4-fluorophenyl group.
ルオロメチルフェニル基である請求項１記載のカルボン
酸エステル又はカルボン酸チオエステルの製造方法。3. The method for producing a carboxylic acid ester or a carboxylic acid thioester according to claim 1, wherein R 6 in the general formula (3) is a 4-trifluoromethylphenyl group.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP17579292A JP3298929B2 (en) | 1992-02-10 | 1992-07-02 | Novel method for producing carboxylic acid ester or carboxylic acid thioester |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2399892 | 1992-02-10 | ||
| JP4-23998 | 1992-02-10 | ||
| JP17579292A JP3298929B2 (en) | 1992-02-10 | 1992-07-02 | Novel method for producing carboxylic acid ester or carboxylic acid thioester |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH05286894A true JPH05286894A (en) | 1993-11-02 |
| JP3298929B2 JP3298929B2 (en) | 2002-07-08 |
Family
ID=26361450
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP17579292A Expired - Fee Related JP3298929B2 (en) | 1992-02-10 | 1992-07-02 | Novel method for producing carboxylic acid ester or carboxylic acid thioester |
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| Country | Link |
|---|---|
| JP (1) | JP3298929B2 (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002036538A1 (en) * | 2000-10-16 | 2002-05-10 | Japan Science And Technology Corporation | Process for producing esterificated condensate |
| JP2006083068A (en) * | 2004-09-14 | 2006-03-30 | Toagosei Co Ltd | Method for producing aromatic ester compound |
| US7847019B2 (en) | 2007-10-15 | 2010-12-07 | California Institute Of Technology | Functionalized polymers using protected thiols |
| WO2015064498A1 (en) * | 2013-10-30 | 2015-05-07 | 三菱レイヨン株式会社 | Phenyl(meta)acrylate production method and phenyl(meta)acrylate composition |
| WO2017090581A1 (en) * | 2015-11-26 | 2017-06-01 | 三菱レイヨン株式会社 | Method for producing carboxylic acid thioester |
-
1992
- 1992-07-02 JP JP17579292A patent/JP3298929B2/en not_active Expired - Fee Related
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002036538A1 (en) * | 2000-10-16 | 2002-05-10 | Japan Science And Technology Corporation | Process for producing esterificated condensate |
| US7301045B2 (en) | 2000-10-16 | 2007-11-27 | Japan Science And Technology Corporation | Method for preparing ester condensate |
| JP2006083068A (en) * | 2004-09-14 | 2006-03-30 | Toagosei Co Ltd | Method for producing aromatic ester compound |
| JP4539250B2 (en) * | 2004-09-14 | 2010-09-08 | 東亞合成株式会社 | Method for producing aromatic ester compound |
| US7847019B2 (en) | 2007-10-15 | 2010-12-07 | California Institute Of Technology | Functionalized polymers using protected thiols |
| US8283438B2 (en) | 2007-10-15 | 2012-10-09 | California Institute Of Technology | Functionalized polymers using protected thiols |
| WO2015064498A1 (en) * | 2013-10-30 | 2015-05-07 | 三菱レイヨン株式会社 | Phenyl(meta)acrylate production method and phenyl(meta)acrylate composition |
| US9771315B2 (en) | 2013-10-30 | 2017-09-26 | Mitsubishi Chemical Corporation | Phenyl (meth)acrylate production method and phenyl (meth)acrylate composition |
| US9783480B2 (en) | 2013-10-30 | 2017-10-10 | Mitsubishi Chemical Corporation | Phenyl (meth)acrylate production method and phenyl (meth)acrylate composition |
| WO2017090581A1 (en) * | 2015-11-26 | 2017-06-01 | 三菱レイヨン株式会社 | Method for producing carboxylic acid thioester |
| JPWO2017090581A1 (en) * | 2015-11-26 | 2018-09-13 | 三菱ケミカル株式会社 | Method for producing carboxylic acid thioester |
| US10377706B2 (en) | 2015-11-26 | 2019-08-13 | Mitsubishi Chemical Corporation | Method for producing carboxylic acid thioester |
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| Publication number | Publication date |
|---|---|
| JP3298929B2 (en) | 2002-07-08 |
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