JPS61251655A - Production of 5-(1-(alkoxycarbonyl)ethyl)-2-phenylthio phenylacetic acid ester - Google Patents
Production of 5-(1-(alkoxycarbonyl)ethyl)-2-phenylthio phenylacetic acid esterInfo
- Publication number
- JPS61251655A JPS61251655A JP9126485A JP9126485A JPS61251655A JP S61251655 A JPS61251655 A JP S61251655A JP 9126485 A JP9126485 A JP 9126485A JP 9126485 A JP9126485 A JP 9126485A JP S61251655 A JPS61251655 A JP S61251655A
- Authority
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- Prior art keywords
- formula
- ethyl
- phenylthio
- acid
- acid ester
- Prior art date
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- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【発明の詳細な説明】
本発明は、抗炎症剤として有用な２−（１０゜１１−ジ
ヒドロ−１０−オキソ、ジベンゾ（ｂ、ｆ）チェピン−
２−イル）プロピオン酸〔ｖ〕の製造のための中間体と
して極めて有用な５−［１−（アルコキシカルブニル）
エチル）−２−フェニルチオ フェニル酢酸エステルｉ
（ｆｆ〕の製造法に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention provides 2-(10°11-dihydro-10-oxo,dibenzo(b,f)chepin-
5-[1-(alkoxycarbunyl) extremely useful as an intermediate for the production of 2-yl)propionic acid [v]
ethyl)-2-phenylthio phenyl acetate i
(ff).
さらに詳しくは一般式ＣＤ
（式中、Ｒ１は低級アルキル基を表す）で表さｎる５−
プロピオニル−２−フェニルチオ ７エ二ル酢酸エステ
ルを、強酸の存在下で、一般式［１）％式％（１１
（式中、Ｒ２はメチル基またはエチル基を表す）１表さ
れるオルトギ酸エステル及び一般式（１）（式中、Ｒ６
は水素原子またはメチル基を表す）１表される。ジアセ
トキシアリールヨードと反応させることを特徴とする一
般式（ＩＴ）
（式中、Ｒ２は前記した基と同一であり、Ｒ４はＲ１ま
たはＲ２はそれぞれ前記した基と同一である）で表され
る５−ＣＩ−（アルコキシカルブニル）エチル）−２−
フェニルチオ フェニル酢酸エステルの製造方法に関す
る。More specifically, 5-5-
Propionyl-2-phenylthio 7enylacetic acid ester was added to the orthoformic acid ester represented by the general formula [1)% formula% (11 (wherein, R2 represents a methyl group or an ethyl group) 1 in the presence of a strong acid. and general formula (1) (wherein, R6
represents a hydrogen atom or a methyl group)1. Represented by the general formula (IT) (wherein, R2 is the same as the group described above, and R4 is the same as the group described above, and R1 or R2 is the same as the group described above), which is characterized by being reacted with diacetoxyaryliodine. 5-CI-(alkoxycarbunyl)ethyl)-2-
The present invention relates to a method for producing phenylthiophenylacetic acid ester.
本発明の製造法は次の反応工程により示される：（式中
、Ｒ４およびＲ２は前記した基と同一′１％あり、Ｒ４
はＲ１またはＲ２を表す）
従１５−（１−（アルコキシカルブニル）エチルツー２
−フェニルチオ フェニル酢酸エステル類を製造する有
用な方法として、例えば特開昭５８−１１３１６８には
下記の方法が記載されている。The production method of the present invention is illustrated by the following reaction steps: (wherein R4 and R2 are 1% identical to the groups described above, R4
represents R1 or R2)
-Phenylthio As a useful method for producing phenylacetic acid esters, the following method is described, for example, in JP-A-58-113168.
しかし、この方法は反応工程が冗長な上に繁雑な操作と
長時間の後処理を必要とする点で工業的に有利な方法と
は言い難い。However, this method cannot be said to be industrially advantageous since the reaction steps are lengthy and require complicated operations and long post-treatments.
本発明者らは、かかる欠点を解決し得る５−（（１−フ
ルコキシカル？ニル）エチル）−２−フェニルチオ フ
ェニル酢酸エステル類ノ新規す製造法について鋭意検討
した結果、経済性に優れかつ製造適性の高い製造法を見
い出し、本発明を完成するに至った。The present inventors have conducted intensive studies on a new method for producing 5-((1-flukoxycarnyl)ethyl)-2-phenylthiophenylacetic acid esters that can solve these drawbacks, and have found that it is highly economical and suitable for production. The present invention was completed by discovering a manufacturing method with high efficiency.
すなわち、本発明の目的は、工業的に有利な５−［１−
（アルコキシカルブニル）エチルツー２−フェニルチオ
フェニル酢酸エステル類の製造法を提供することにｓ
ｂ、その特徴とするところは、一般式（１）ｒ表される
５−プロピオニル−２−７エールチオフエニル酢酸を原
料とし、強酸の存在下、一般式（ｎ）で表されるオルト
ギ酸エステル及び一般式（１）で表されるジアセトキシ
アリールヨードと反応させて一般式（ＩＶ）’ｔ’表さ
れる５−〔１−（アルコキシカルブニル）エチル）−２
−フェニルチオフェニル酢酸エステルを得ることにある
。That is, the object of the present invention is to obtain an industrially advantageous 5-[1-
To provide a method for producing (alkoxycarbyl)ethyl-2-phenylthiophenylacetic acid esters.
b. Its characteristics are that 5-propionyl-2-7 ethiophenylacetic acid represented by general formula (1)r is used as a raw material, and orthoformic acid represented by general formula (n) is produced in the presence of a strong acid. 5-[1-(alkoxycarbunyl)ethyl)-2 represented by general formula (IV) 't' by reacting with an ester and a diacetoxyaryliodine represented by general formula (1)
- To obtain phenylthiophenyl acetate.
例えば、本発明の実施において使用する強酸としては、
濃硫酸、Ｐ−トルエンスルホン酸の如き有機スルホン酸
、及びポリスチレンスルホン酸やＮａｆｉｏｎ（商品名
、アルドリッチ社ｆｆ）の如きスルホン酸基を有する高
分子担体が有用ｆある。使用量については酸の種類によ
って異なるが、例えば濃硫酸の場合、化合物（Ｉｌｌに
対して０．５〜６．５倍モル、好ましくは１．０〜２．
５倍モル使用するのが適当である。また化合物（ｎ）で
表されるオルトギ酸エステルは、反応溶媒を兼ねて過剰
に使用するのが有利である。For example, strong acids used in the practice of the present invention include:
Concentrated sulfuric acid, organic sulfonic acids such as P-toluenesulfonic acid, and polymeric carriers having sulfonic acid groups such as polystyrene sulfonic acid and Nafion (trade name, Aldrich Co., Ltd.) are useful. The amount used varies depending on the type of acid, but for example, in the case of concentrated sulfuric acid, it is 0.5 to 6.5 times the mole of the compound (Ill, preferably 1.0 to 2.
It is appropriate to use 5 times the molar amount. Further, it is advantageous to use the orthoformic acid ester represented by compound (n) in excess so that it also serves as a reaction solvent.
さらに化合物〔夏〕で表わされるジアセトキシアリール
ヨードは、化合物（Ｉｌｌに対して１．０〜５．０倍モ
ル、好ましくは１．１〜１．６倍モル使用することがで
きる。Further, the diacetoxyaryl iodo represented by the compound [Natsu] can be used in an amount of 1.0 to 5.0 times the mole, preferably 1.1 to 1.6 times the mole of the compound (Ill).
反応温度は４０〜１００Ｃが好ましいう所定の時間反応
した後、反応混合物を水中に注加し、適当な有機溶媒、
例えば酢酸エチルの如きエステル類、トルエン、キシレ
ンの如き芳香族炭化水素、エチルエーテルの如きエーテ
ル類、塩化メチレンの如きハロゲン化炭化水素類を用い
て抽出、水洗後溶媒を留去して目的物〔■〕を高収率で
得ることができる。尚、出発物質〔■〕とオルトギ酸エ
ステル（ＩＤの組み合せによっては、反応中エステル交
換がおこることがある為、生成物が２〜４種のジエステ
ル混合物として得られることもある。このことは抗炎症
剤として有用な２−（１０，１１，−、ジヒドロ−１０
−オキンジペンゾ［ｂ、ｆ］チェピン−２−イル）プロ
ピオン酸を製造する上〒、何んら不都合を与えない。The reaction temperature is preferably 40 to 100C. After reacting for a predetermined time, the reaction mixture is poured into water, and a suitable organic solvent,
For example, extraction is performed using esters such as ethyl acetate, aromatic hydrocarbons such as toluene and xylene, ethers such as ethyl ether, and halogenated hydrocarbons such as methylene chloride. After washing with water, the solvent is distilled off to obtain the desired product. (2)] can be obtained in high yield. Note that depending on the combination of starting material [■] and orthoformic acid ester (ID), transesterification may occur during the reaction, so the product may be obtained as a mixture of 2 to 4 types of diesters. 2-(10,11,-,dihydro-10) useful as an inflammatory agent
-Oquinedipenzo[b,f]chepin-2-yl)propionic acid is produced without causing any inconvenience.
５−プロピオニル−２−フェニルチオ フェニル酢酸エ
ステルを原料とする従来の５−（１−（アルコキシカル
ゼニル）エチル）−２−フェニルチオ フェニル酢酸エ
ステル類の製造法は、反応工程が長い上に、繁雑な操作
と長時間の後処理を必要とするなど、工業的に有利な方
法とは言い難い。The conventional method for producing 5-(1-(alkoxycarzenyl)ethyl)-2-phenylthiophenylacetates using 5-propionyl-2-phenylthiophenylacetate as a raw material requires a long reaction process and is complicated. It cannot be said to be an industrially advantageous method as it requires operations and long post-treatments.
これに対して、本発明は、同一原料かられずか１工程で
目的とするジエステルが得られ、しかも特別な設備を必
要とせず、操作も非常に簡単、安全で、公知技術に比べ
著しく優れた製造方法である。In contrast, the present invention allows the desired diester to be obtained from the same raw materials in just one step, does not require special equipment, is extremely simple and safe to operate, and is significantly superior to known techniques. This is the manufacturing method.
以下実施例によって本発明を説明するが、本発明はこの
実施例に限定されるものではない。The present invention will be explained below with reference to Examples, but the present invention is not limited to these Examples.
実施例 １
ｓ−Ｃ１−（エトキシカルゼニル）エチル〕＝２−フェ
ニルチオ フェニル酢酸エチルの合成（（ＩＶ） ：
Ｒ１＝ Ｒ２＝エチル）５−プロピオニル−２−フェニ
ルチオ フェニル酢酸エチル１６．４１１ （０，０５
ｍｏｌ ）、・ジアセトキシフェニルヨード１９．６１
（０，０６ｍｏｌ）およびオルトギ酸エチル１５０ｍ
１の混合溶液に、濃硫酸９．８ｇ（Ｑｉ Ｏｍｏｆ）を
滴下して、６ａＣで２時間攪拌した。これを氷水５００
ｍ１に投入し、酢酸エチルで抽出、つい〒水洗し芒硝〒
乾燥後、減圧濃縮した。Example 1 Synthesis of s-C1-(ethoxycarzenyl)ethyl]=2-phenylthio ethyl phenylacetate ((IV):
R1= R2=ethyl) 5-propionyl-2-phenylthio ethyl phenylacetate 16.411 (0,05
mol ), diacetoxyphenyl iodide 19.61
(0.06 mol) and ethyl orthoformate 150 m
9.8 g of concentrated sulfuric acid (Qi Omof) was added dropwise to the mixed solution of 1, and the mixture was stirred at 6aC for 2 hours. Add this to 500 ml of ice water
m1, extracted with ethyl acetate, washed with water, and dissolved in mirabilite.
After drying, it was concentrated under reduced pressure.
残留物を蒸留（沸点： １８３〜１８５Ｃ１０，２ｍｍ
Ｈｌｉ＋）し淡黄色の油状物質１５．８．９（収率８５
％）を得た。Distill the residue (boiling point: 183-185C10.2mm
Hli+) pale yellow oily substance 15.8.9 (yield 85
%) was obtained.
ＮＭＲスペクトル（重クロロホルムｍ液）：δ ：
１．０ 〜１．５ （９Ｈ，ｍ）３．５ 〜４．２
（７Ｈ，ｍ）
７．０ 〜７．４ （８Ｈ，ｍ）
実施例 ２
５−（１−（メ）キシカルゼニル）エチル〕−２−フェ
ニルチオ フェニル酢酸メチルの合成（Ｃｒ’ｌ’Ｊ
： Ｒ１＝ Ｒ２＝メチル）５−７’ロヒオニル−２−
フェニルチオ ７エ二ル酢酸メチル１２．６１ （０，
０４ｍｏｌ）、ジアセトキシフェニルヨード１５．５１
１ （０，０５ｍｏｌ）およびオルトギ酸エチル１００
ｍ１の混合溶液に、濃硫酸７．８１ （０，０８ｍｏｆ
）を滴下して、６（１−ｔ％６時間攪拌した。これを氷
水４００ｍ１ に投入し、酢酸エチルで抽出、ついで水
洗した芒硝〒乾燥後、減圧濃縮した。NMR spectrum (deuterated chloroform solution): δ:
1.0 ~ 1.5 (9H, m) 3.5 ~ 4.2
(7H, m) 7.0 - 7.4 (8H, m) Example 2 Synthesis of 5-(1-(meth)xycarzenyl)ethyl]-2-phenylthio methyl phenylacetate (Cr'l'J
: R1= R2=methyl)5-7'rohionyl-2-
Phenylthio 7-enylacetate methyl 12.61 (0,
04 mol), diacetoxyphenyl iodide 15.51
1 (0.05 mol) and ethyl orthoformate 100
Add 7.81 m of concentrated sulfuric acid (0.08 mof
) was added dropwise and stirred for 6 hours. This was poured into 400 ml of ice water, extracted with ethyl acetate, washed with water, dried, and concentrated under reduced pressure.
残留物を蒸留（沸点： １７５〜１７７Ｃ１０，２ｍｍ
Ｈｇ）し淡黄色の油状物質１ｔｓｇ（収率８４％）を得
たＯ
ＮＭＲ，（ペク）ル（重クロロホルム？Ｍ）：δ ：
１．４ （３ＩＴ、ｄ）３．６
（！Ｈ，ｓ）
３．７ （３Ｈ，ｓ）
３．７５ （１１（、Ｑ〆）
５．８ （２Ｈ，ｓ）
７、（１−７，４（８Ｈ，ｍ）
（ほか６名）Distill the residue (boiling point: 175-177C10.2mm
Hg) and obtained 1 tsg (yield 84%) of a pale yellow oily substance. O NMR, (deuterochloroform?M): δ:
1.4 (3IT, d) 3.6
(!H,s) 3.7 (3H,s) 3.75 (11(,Q〆) 5.8 (2H,s) 7, (1-7,4(8H,m) (6 others)
Claims (4)
ル酢酸エステルを、強酸の存在下で、一般式〔II〕 ＣＨ（ＯＲ＿２）＿３〔II〕 （式中、Ｒ＿２はメチル基またはエチル基を表す）で表
されるオルトギ酸エステル及び一般式〔III〕▲数式、
化学式、表等があります▼〔III〕 （式中、Ｒ＿３は水素原子またはメチル基を表す）で表
されるジアセトキシアリールヨードと反応させることを
特徴とする一般式〔IV〕 ▲数式、化学式、表等があります▼〔IV〕 （式中、Ｒ＿２は前記した基と同一であり、Ｒ＿４はＲ
＿２を表し、Ｒ＿１およびＲ＿２はそれぞれ前記した基
と同一である） で表される５−〔１−（アルコキシカルボニル）エチル
〕−２−フェニルチオフェニル酢酸エステルの製造法。(1) General formula [I] ▲There are mathematical formulas, chemical formulas, tables, etc.▼[I] (In the formula, R_1 represents a lower alkyl group) 5-propionyl-2-phenylthiophenyl acetate, In the presence of a strong acid, the orthoformate ester represented by the general formula [II] CH(OR_2)_3[II] (in the formula, R_2 represents a methyl group or an ethyl group) and the general formula [III]▲mathematical formula,
There are chemical formulas, tables, etc. ▼ [III] (In the formula, R_3 represents a hydrogen atom or a methyl group) General formula characterized by reaction with diacetoxyaryliodine [IV] ▲ Numerical formula, chemical formula, There are tables, etc. ▼ [IV] (In the formula, R_2 is the same as the above group, and R_4 is R
_2, R_1 and R_2 are each the same as the above-mentioned group) A method for producing 5-[1-(alkoxycarbonyl)ethyl]-2-phenylthiophenyl acetate.
る特許請求の範囲第一項記載の方法。(2) The method according to claim 1, wherein in the general formula [I], R_1 is an ethyl group.
る特許請求の範囲第一項記載の方法。(3) The method according to claim 1, wherein in the general formula [I], R_1 is a methyl group.
方法。(4) The method according to claim 1, wherein the strong acid is concentrated sulfuric acid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP9126485A JPS61251655A (en) | 1985-04-30 | 1985-04-30 | Production of 5-(1-(alkoxycarbonyl)ethyl)-2-phenylthio phenylacetic acid ester |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP9126485A JPS61251655A (en) | 1985-04-30 | 1985-04-30 | Production of 5-(1-(alkoxycarbonyl)ethyl)-2-phenylthio phenylacetic acid ester |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS61251655A true JPS61251655A (en) | 1986-11-08 |
Family
ID=14021561
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP9126485A Pending JPS61251655A (en) | 1985-04-30 | 1985-04-30 | Production of 5-(1-(alkoxycarbonyl)ethyl)-2-phenylthio phenylacetic acid ester |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS61251655A (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61227561A (en) * | 1985-03-30 | 1986-10-09 | Nippon Chemiphar Co Ltd | Production of 5-(1-carboxyethyl)-2-phenylthiophenylacetic acid derivative |
-
1985
- 1985-04-30 JP JP9126485A patent/JPS61251655A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61227561A (en) * | 1985-03-30 | 1986-10-09 | Nippon Chemiphar Co Ltd | Production of 5-(1-carboxyethyl)-2-phenylthiophenylacetic acid derivative |
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