JPH08198843A - Production of sulfenylacetic acid derivative - Google Patents
Production of sulfenylacetic acid derivativeInfo
- Publication number
- JPH08198843A JPH08198843A JP7025807A JP2580795A JPH08198843A JP H08198843 A JPH08198843 A JP H08198843A JP 7025807 A JP7025807 A JP 7025807A JP 2580795 A JP2580795 A JP 2580795A JP H08198843 A JPH08198843 A JP H08198843A
- Authority
- JP
- Japan
- Prior art keywords
- mmol
- added
- acetic acid
- acid
- ethyl acetate
- 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
-
- 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
Landscapes
- Furan Compounds (AREA)
- 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、一般式FIELD OF THE INVENTION The present invention has the general formula
【０００２】[0002]
【化４】 [Chemical 4]
【０００３】（式中Ｒ1 は、置換若しくは無置換の芳香
族炭化水素又は置換若しくは無置換の芳香族複素環基で
あり、Ｒ3 は、水酸基、アルコキシ基又はアミノ基であ
る。）で表されるスルフェニル酢酸誘導体の製造法に関
する。(Wherein R 1 is a substituted or unsubstituted aromatic hydrocarbon or a substituted or unsubstituted aromatic heterocyclic group, and R 3 is a hydroxyl group, an alkoxy group or an amino group). And a method for producing a sulfenylacetic acid derivative.
【０００４】[0004]
【従来の技術】前記一般式（Ｉ）で表されるスルフェニ
ル酢酸誘導体は、医薬品、農薬或いは各種機能材料など
の製造中間体として有用な化合物であり、例えば、抗消
化性潰瘍剤を製造するための中間体として知られてい
る。（特開昭６２−１５３２６８号公報）、（特開昭６
２−１５３２７９号公報）、（特開平−２３５７６号公
報）従来、前記一般式（Ｉ）で表されるスルフェニル酢
酸誘導体は、例えば、メルカプタン誘導体とクロロ酢酸
誘導体との反応により製造されていた。2. Description of the Related Art The sulfenylacetic acid derivative represented by the general formula (I) is a compound useful as an intermediate for the production of pharmaceuticals, agricultural chemicals, various functional materials and the like, for example, an anti-peptic ulcer agent is produced. Known as an intermediate for (JP-A-62-153268), (JP-A-6-63)
Conventionally, the sulfenylacetic acid derivative represented by the general formula (I) has been produced, for example, by reacting a mercaptan derivative with a chloroacetic acid derivative.
【０００５】[0005]
【発明が解決しようとする課題】しかしながら、従来製
造法に於いては、副生成物が多く且つメルカプタン誘導
体が高価である等、工業的製造法としては問題の多い方
法であった。However, the conventional production method has many problems as an industrial production method such as a large amount of by-products and an expensive mercaptan derivative.
【０００６】[0006]
【課題を解決するための手段】本発明者等は、従来の問
題点を解決すべく検討の結果、工業的に安価に入手でき
るアルコ−ル誘導体とメルカプタン誘導体とをルイス酸
触媒存在下反応させることにより、高収率でスルフェニ
ル酢酸誘導体を製造できる経済的方法を見い出し本発明
を完成した。Means for Solving the Problems As a result of studies to solve the conventional problems, the present inventors have made an alcohol derivative and a mercaptan derivative, which are industrially available at low cost, react with each other in the presence of a Lewis acid catalyst. As a result, an economical method capable of producing a sulfenylacetic acid derivative with a high yield was found, and the present invention was completed.
【０００７】本発明は、一般式The present invention has the general formula
【０００８】[0008]
【化５】 Embedded image
【０００９】（式中、Ｒ1 は、置換若しくは無置換の芳
香族炭化水素又は置換若しくは無置換の芳香族複素環基
であり、Ｒ2 は、水素原子、アシル基又はアルキル基で
ある。）で表されるアルコール誘導体と一般式(In the formula, R 1 is a substituted or unsubstituted aromatic hydrocarbon or a substituted or unsubstituted aromatic heterocyclic group, and R 2 is a hydrogen atom, an acyl group or an alkyl group.) Alcohol derivative represented by
【００１０】[0010]
【化６】 [Chemical 6]
【００１１】（式中Ｒ3 は、水酸基、アルコキシ基又は
アミノ基である。）で表されるメルカプタン誘導体とを
ルイス酸存在下反応させ、一般式（Ｉ）で表されるスル
フェニル酢酸誘導体を製造するものである。A mercaptan derivative represented by the formula (R 3 is a hydroxyl group, an alkoxy group or an amino group) is reacted in the presence of a Lewis acid to give a sulfenylacetic acid derivative represented by the general formula (I). It is manufactured.
【００１２】本発明の原料である前記一般式（II）で表
されるアルコール誘導体は、市販又は容易に入手可能な
化合物であり、例えば、フルフリルアルコール、フルフ
リル＝アセテート、フルフリル＝プロピオネート、フル
フリル＝ブチレート、フルフリル＝ベンゾエート、フル
フリル＝p-メトキシベンゾエート、フルフリルメチル＝
テレフタレート、フルフリル＝p-ニトロベンゾエート、
フルフリルエチル＝カルボネート、フルフリル＝ピバレ
ート、フルフリルメチルエーテル、フルフリルエチルエ
ーテル、フルフリルプロピルエーテル、フルフリルブチ
ルエーテル、フルフリルフェニルエーテル、３−フリル
メチルアルコール、３−フリルメチル＝アセテート、３
−フリルメチル＝プロピオネート、３−フリルメチル＝
ブチレート、３−フリルメチル＝ベンゾエート、３−フ
リルメチルメチルエーテル、３−フリルメチルエチルエ
ーテル、３−フリルメチルプロピルエーテル、３−フリ
ルメチルブチルエーテル、３−フリルメチルフェニルエ
ーテル、The alcohol derivative represented by the above general formula (II), which is a raw material of the present invention, is a commercially available or readily available compound, and examples thereof include furfuryl alcohol, furfuryl acetate, furfuryl propionate, and furfuryl. Butyrate, furfuryl benzoate, furfuryl = p-methoxybenzoate, furfuryl methyl =
Terephthalate, furfuryl = p-nitrobenzoate,
Furfurylethyl carbonate, furfuryl pivalate, furfuryl methyl ether, furfuryl ethyl ether, furfuryl propyl ether, furfuryl butyl ether, furfuryl phenyl ether, 3-furyl methyl alcohol, 3-furyl methyl acetate, 3
-Furylmethyl = propionate, 3-furylmethyl =
Butyrate, 3-furylmethyl benzoate, 3-furylmethyl methyl ether, 3-furylmethyl ethyl ether, 3-furylmethyl propyl ether, 3-furyl methyl butyl ether, 3-furyl methyl phenyl ether,
【００１３】２−テニルアルコール、２−テニル＝アセ
テート、２−テニル＝プロピオネート、２−テニル＝ブ
チレート、２−テニル＝ベンゾエート、２−テニルメチ
ルエーテル、２−テニルエチルエーテル、２−テニルプ
ロピルエーテル、２−テニルブチルエーテル、２−テニ
ルフェニルエーテル、３−テニルアルコール、３−テニ
ル＝アセテート、３−テニル＝プロピオネート、３−テ
ニル＝ブチレート、３−テニル＝ベンゾエート、３−テ
ニルメチルエーテル、３−テニルエチルエーテル、３−
テニルプロピルエーテル、３−テニルブチルエーテル、
３−テニルフェニルエーテル、ベンジルアルコール、ベ
ンジル＝アセテート、ベンジル＝プロピオネート、ベン
ジル＝ブチレート、ベンジル＝ベンゾエート、ベンジル
メチルエーテル、ベンジルエチルエーテル、ベンジルプ
ロピルエーテル、ベンジルブチルエーテル、ベンジルフ
ェニルエーテル、2-Tenyl alcohol, 2-Tenyl acetate, 2-Tenyl propionate, 2-Tenyl butyrate, 2-Tenyl benzoate, 2-Tenyl methyl ether, 2-Tenyl ethyl ether, 2-Tenyl propyl ether, 2-Tenyl butyl ether, 2-Tenyl phenyl ether, 3-Tenyl alcohol, 3-Tenyl acetate, 3-Tenyl propionate, 3-Tenyl butyrate, 3-Tenyl benzoate, 3-Tenyl methyl ether, 3-Tenyl ethyl. Ether, 3-
Tenyl propyl ether, 3-tenyl butyl ether,
3-tenyl phenyl ether, benzyl alcohol, benzyl acetate, benzyl propionate, benzyl butyrate, benzyl benzoate, benzyl methyl ether, benzyl ethyl ether, benzyl propyl ether, benzyl butyl ether, benzyl phenyl ether,
【００１４】２−ピリジルメチルアルコール、２−ピリ
ジルメチル＝アセテート、２−ピリジルメチル＝プロピ
オネート、２−ピリジルメチル＝ブチレート、２−ピリ
ジルメチル＝ベンゾエート、２−ピリジルメチルメチル
エーテル、２−ピリジルメチルエチルエーテル、２−ピ
リジルメチルプロピルエーテル、２−ピリジルメチルブ
チルエーテル、２−ピリジルメチルフェニルエーテル、
３−ピリジルメチルアルコール、３−ピリジルメチル＝
アセテート、３−ピリジルメチル＝プロピオネート、３
−ピリジルメチル＝ブチレート、３−ピリジルメチル＝
ベンゾエート、３−ピリジルメチルメチルエーテル、３
−ピリジルメチルエチルエーテル、３−ピリジルメチル
プロピルエーテル、３−ピリジルメチルブチルエーテ
ル、３−ピリジルメチルフェニルエーテル、４−ピリジ
ルメチルアルコール、４−ピリジルメチルアセテート、
４−ピリジルメチル＝プロピオネート、４−ピリジルメ
チル＝ブチレート、４−ピリジルメチル＝ベンゾエー
ト、４−ピリジルメチルメチルエーテル、４−ピリジル
メチルエチルエーテル、４−ピリジルメチルプロピルエ
ーテル、４−ピリジルメチルブチルエーテル、４−ピリ
ジルメチルフェニルエーテル、2-pyridylmethyl alcohol, 2-pyridylmethyl acetate, 2-pyridylmethyl propionate, 2-pyridylmethyl butyrate, 2-pyridylmethyl benzoate, 2-pyridylmethyl methyl ether, 2-pyridylmethyl ethyl ether , 2-pyridylmethylpropyl ether, 2-pyridylmethylbutyl ether, 2-pyridylmethylphenyl ether,
3-pyridylmethyl alcohol, 3-pyridylmethyl =
Acetate, 3-pyridylmethyl propionate, 3
-Pyridylmethyl = butyrate, 3-pyridylmethyl =
Benzoate, 3-pyridylmethyl methyl ether, 3
-Pyridyl methyl ethyl ether, 3-pyridyl methyl propyl ether, 3-pyridyl methyl butyl ether, 3-pyridyl methyl phenyl ether, 4-pyridyl methyl alcohol, 4-pyridyl methyl acetate,
4-pyridylmethyl propionate, 4-pyridylmethyl butyrate, 4-pyridylmethyl benzoate, 4-pyridylmethyl methyl ether, 4-pyridylmethyl ethyl ether, 4-pyridylmethyl propyl ether, 4-pyridylmethyl butyl ether, 4- Pyridyl methyl phenyl ether,
【００１５】１−ナフチルメチルアルコール、１−ナフ
チルメチル＝アセテート、１−ナフチルメチル＝プロピ
オネート、１−ナフチルメチル＝ブチレート、１−ナフ
チルメチル＝ベンゾエート、１−ナフチルメチルメチル
エーテル、１−ナフチルメチルエチルエーテル、１−ナ
フチルメチルプロピルエーテル、１−ナフチルメチルブ
チルエーテル、１−ナフチルメチルフェニルエーテル、
２−ナフチルメチルアルコール、２−ナフチルメチル＝
アセテート、２−ナフチルメチル＝プロピオネート、２
−ナフチルメチル＝ブチレート、２−ナフチルメチル＝
ベンゾエート、２−ナフチルメチルメチルエーテル、２
−ナフチルメチルエチルエーテル、２−ナフチルメチル
プロピルエーテル、２−ナフチルメチルブチルエーテ
ル、２−ナフチルメチルフェニルエーテル等を使用する
ことができる。1-naphthylmethyl alcohol, 1-naphthylmethyl acetate, 1-naphthylmethyl propionate, 1-naphthylmethyl butyrate, 1-naphthylmethyl benzoate, 1-naphthylmethyl methyl ether, 1-naphthylmethyl ethyl ether , 1-naphthyl methyl propyl ether, 1-naphthyl methyl butyl ether, 1-naphthyl methyl phenyl ether,
2-naphthylmethyl alcohol, 2-naphthylmethyl =
Acetate, 2-naphthylmethyl propionate, 2
-Naphthylmethyl = butyrate, 2-naphthylmethyl =
Benzoate, 2-naphthylmethyl methyl ether, 2
-Naphthyl methyl ethyl ether, 2-naphthyl methyl propyl ether, 2-naphthyl methyl butyl ether, 2-naphthyl methyl phenyl ether, etc. can be used.
【００１６】更に一方の原料である前記一般式（III ）
で表されるメルカプタン誘導体も、市販又は容易に入手
可能な化合物であり、例えば、チオグリコール酸、チオ
グリコール酸メチル、チオグリコール酸エチル、チオグ
リコール酸プロピル、チオグリコール酸ブチル、メルカ
プトアセタミド、Ｎ−メチルメルカプトアセタミド、Ｎ
−エチルメルカプトアセタミド、Ｎ−プロピルメルカプ
トアセタミド、Ｎ−ブチルメルカプトアセタミド、Ｎ−
フェニルメルカプトアセタミド、Ｎ−ベンジルメルカプ
トアセタミド、Ｎ、Ｎ−ジメチルメルカプトアセタミ
ド、Ｎ、Ｎ−ジエチルメルカプトアセタミド、Ｎ、Ｎ−
ジプロピルメルカプトアセタミド、Ｎ、Ｎ−ジフェニル
メルカプトアセタミド、Ｎ、Ｎ−ジベンジルメルカプト
アセタミド等を使用することができる。Further, the above-mentioned general formula (III) which is one of the starting materials
The mercaptan derivative represented by is also a commercially available or easily available compound, for example, thioglycolic acid, methyl thioglycolate, ethyl thioglycolate, propyl thioglycolate, butyl thioglycolate, mercaptoacetamide, N-methylmercaptoacetamide, N
-Ethylmercaptoacetamide, N-propylmercaptoacetamide, N-butylmercaptoacetamide, N-
Phenylmercaptoacetamide, N-benzylmercaptoacetamide, N, N-dimethylmercaptoacetamide, N, N-diethylmercaptoacetamide, N, N-
Dipropylmercaptoacetamide, N, N-diphenylmercaptoacetamide, N, N-dibenzylmercaptoacetamide and the like can be used.
【００１７】前記一般式（II）で表されるアルコール誘
導体と前記一般式（III ）で表されるメルカプタン誘導
体との反応で使用されるルイス酸としては、例えば、塩
化亜鉛、ヨウ化亜鉛、トリフルオロメタンスルホン酸亜
鉛、過塩素酸リチウム、三フッ化ホウ素、三塩化ホウ
素、トリメチルホウ素、三酸化硫黄、四フッ化硫黄、四
フッ化セレン、臭化第二鉄、三塩化アルミニウム、ジエ
チル塩化アルミニウム、メチル塩化アルミニウム、リチ
ウムテトラフルオロボレート、三フッ化アルミニウム、
塩化スズ、三塩化リン、塩化チタン、臭化マグネシウ
ム、トリフルオロメタンスルホン酸イッテルビウム等を
用いることができる。The Lewis acid used in the reaction between the alcohol derivative represented by the general formula (II) and the mercaptan derivative represented by the general formula (III) is, for example, zinc chloride, zinc iodide or trifluoride. Zinc methanesulfonate, lithium perchlorate, boron trifluoride, boron trichloride, trimethylboron, sulfur trioxide, sulfur tetrafluoride, selenium tetrafluoride, ferric bromide, aluminum trichloride, diethyl aluminum chloride, Methyl aluminum chloride, lithium tetrafluoroborate, aluminum trifluoride,
Tin chloride, phosphorus trichloride, titanium chloride, magnesium bromide, ytterbium trifluoromethanesulfonate, etc. can be used.
【００１８】ルイス酸の使用量は、前記したメルカプタ
ン誘導体に対し０．００１−１等量が好ましい。反応
は、溶媒中行うことが望ましく、例えば、クロロホル
ム、ジクロロメタン等のハロゲン化炭化水素類、ベンゼ
ン、トルエン等の芳香族炭化水素類、テトラヒドロフラ
ン、ジオキサン、ジメトキシエタン等のエーテル類、ア
セトニトリル、プロピオニトリル等のニトリル類、アセ
トン、メチルエチルケトン等のケトン類を好適に用いる
ことができる。反応は−７８℃−１５０℃で円滑に進行
する。The Lewis acid is preferably used in an amount of 0.001-1 equivalent to the mercaptan derivative. The reaction is preferably carried out in a solvent, for example, halogenated hydrocarbons such as chloroform and dichloromethane, aromatic hydrocarbons such as benzene and toluene, ethers such as tetrahydrofuran, dioxane and dimethoxyethane, acetonitrile, propionitrile. And the like, and ketones such as acetone and methyl ethyl ketone can be preferably used. The reaction proceeds smoothly at -78 ° C to 150 ° C.
【００１９】[0019]
【実施例】以下参考例及び実施例により本発明を更に詳
細に説明する。 （参考例１） ４−アニス酸フルフリルエステルThe present invention will be described in more detail with reference to the following Reference Examples and Examples. Reference Example 1 4-anisic acid furfuryl ester
【００２０】[0020]
【化７】 [Chemical 7]
【００２１】窒素気流下０℃でフルフリルアルコ−ル５
ｇ（５１ｍｍｏｌ）の無水塩化メチレン３５溶液にジメ
チルアミノピリジン６２ g（０．５１ｍｏｌ) とトリエ
チルアミン１０ｍｌ（７６ｍｍｏｌ) を加え、そのまま
１０分撹拌した。次いでこの溶液に４−アニス酸クロリ
ド１１．３ｇ（６６ｍｍｏｌ）を滴下し、同温で３０分
撹拌した。反応終了後、反応混液に飽和塩化アンモニウ
ム水を加え有機層を分取し、水層を塩化メチレンで抽出
（３回）した。有機層を合わせ飽和食塩水で洗浄し、無
水硫酸ナトリウムで乾燥後溶媒を留去した。残留物をシ
リカゲルカラムクロマトグラフィーに付し、ヘキサン−
酢酸エチル（１９：１）溶出液より４−アニス酸フルフ
リルエステル１１．７ｇ（収率９８％）を得た。1 H-NMR(δ,CDCl3 ):3.85(3H,s),5.28(2H,s),6.38(1H,d
d,J=1.9,3.2Hz),6.47(1H,d, J=3.2Hz),6.90(2H,d,J=9.0
Hz),7.45(1H,d,J=1.9Hz),8.01(2H,d,J=9.0Hz). IR(νcm-1,neat):1714,1608,1514,1256,1168,1096,103
0,920,848,770,746.Furfuryl alcohol 5 at 0 ° C. under nitrogen stream
To a solution of g (51 mmol) in anhydrous methylene chloride 35 was added 62 g (0.51 mol) of dimethylaminopyridine and 10 ml (76 mmol) of triethylamine, and the mixture was stirred for 10 minutes as it was. Next, 11.3 g (66 mmol) of 4-anisyl chloride was added dropwise to this solution, and the mixture was stirred at the same temperature for 30 minutes. After completion of the reaction, saturated aqueous ammonium chloride was added to the reaction mixture, the organic layer was separated, and the aqueous layer was extracted with methylene chloride (three times). The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated. The residue was subjected to silica gel column chromatography, and hexane-
4-ethylanis furfuryl ester 11.7 g (yield 98%) was obtained from an ethyl acetate (19: 1) eluate. 1 H-NMR (δ, CDCl 3 ): 3.85 (3H, s), 5.28 (2H, s), 6.38 (1H, d
d, J = 1.9,3.2Hz), 6.47 (1H, d, J = 3.2Hz), 6.90 (2H, d, J = 9.0
Hz), 7.45 (1H, d, J = 1.9Hz), 8.01 (2H, d, J = 9.0Hz) .IR (νcm -1 , neat): 1714,1608,1514,1256,1168,1096,103
0,920,848,770,746.
【００２２】（参考例２） ４−メトキシカルボニル安息香酸フルフリルエステルReference Example 2 4-Methoxycarbonylbenzoic acid furfuryl ester
【００２３】[0023]
【化８】 Embedded image
【００２４】窒素気流下モノテレフタル酸メチルエステ
ル１ｇ（５．６ｍｍｏｌ）の塩化チオニル２ｍｌ（２
７．８ｍｍｏｌ）溶液に無水ジメチルホルムアミドを一
滴加え、５時間加熱還流した。反応終了後塩化チオニル
を留去し未精製の酸クロリドを得た。窒素気流下０℃で
フルフリルアルコ−ル５４５ｍｇ（５．６ｍｍｏｌ) の
無水塩化メチレン３ｍｌ溶液にジメチルアミノピリジン
７ｍｇ（０．０６ｍｍｏｌ）とトリエチルアミン１．５
５ｍｌ（１１．１ｍｍｏｌ) を加え、そのまま１０分撹
拌した。次いでこの溶液に先に調製した酸クロリドを塩
化メチレン２ｍｌに溶解し滴下し、同温で３０分撹拌し
た。反応終了後、反応混液に飽和塩化アンモニウム水を
加え有機層を分取し、水層を塩化メチレンで抽出（３
回）した。有機層を合わせ飽和食塩水で洗浄し、無水硫
酸ナトリウムで乾燥後溶媒を留去した。残留物をシリカ
ゲルカラムクロマトグラフィーに付し、ヘキサン−酢酸
エチル（１９：１）溶出液より４−メトキシカルボニル
安息香酸フルフリルエステル１．１ｇ（収率７６％）を
得た。1 H-NMR(δ,CDCl3):3.94(3H,s),5.33(2H,s),6.40(1H,dd,
J=1.9,3.3Hz),6.51(1H,d,J=3.3Hz),7.46(1H,d,J=1.9H
z),8.06-8.16(4H,m). IR(νcm-1,KBr):1728,1506,1438,1410,1284,1120,1018,
954,932.Under a stream of nitrogen, 1 g (5.6 mmol) of monoterephthalic acid methyl ester and 2 ml of thionyl chloride (2
A drop of anhydrous dimethylformamide was added to the solution (7.8 mmol) and the mixture was heated under reflux for 5 hours. After completion of the reaction, thionyl chloride was distilled off to obtain crude acid chloride. Under a nitrogen stream at 0 ° C., furfuryl alcohol 545 mg (5.6 mmol) in anhydrous methylene chloride 3 ml solution was added with dimethylaminopyridine 7 mg (0.06 mmol) and triethylamine 1.5.
5 ml (11.1 mmol) was added and the mixture was stirred as it was for 10 minutes. Next, the acid chloride prepared above was dissolved in 2 ml of methylene chloride and added dropwise to this solution, and the mixture was stirred at the same temperature for 30 minutes. After the reaction was completed, saturated aqueous ammonium chloride was added to the reaction mixture, the organic layer was separated, and the aqueous layer was extracted with methylene chloride (3
Times) The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated. The residue was subjected to silica gel column chromatography, and 1.1 g (yield: 76%) of 4-methoxycarbonylbenzoic acid furfuryl ester was obtained from a hexane-ethyl acetate (19: 1) eluate. 1 H-NMR (δ, CDCl 3 ): 3.94 (3H, s), 5.33 (2H, s), 6.40 (1H, dd,
J = 1.9,3.3Hz), 6.51 (1H, d, J = 3.3Hz), 7.46 (1H, d, J = 1.9H
z), 8.06-8.16 (4H, m) .IR (νcm -1 ,, KBr): 1728,1506,1438,1410,1284,1120,1018,
954,932.
【００２５】（参考例３） ピバリン酸フルフリルエステルReference Example 3 Pivalic acid furfuryl ester
【００２６】[0026]
【化９】 [Chemical 9]
【００２７】窒素気流下０℃でフルフリルアルコ−ル２
ｇ（２０．４ｍｍｏｌ) の無水塩化メチレン１０ｍｌ溶
液にジメチルアミノピリジン２５ｍｇ（０．２ｍｍｏ
ｌ）とトリエチルアミン４．３ｍｌ（３０．６ｍｍｏ
ｌ）を加え、そのまま10分撹拌した。次いでこの溶液に
ピバリン酸クロリド３．３ｍｌ（２６．５ｍｍｏｌ）を
滴下し、同温で３０分撹拌した。反応終了後、反応混液
に飽和塩化アンモニウム水を加え有機層を分取し、水層
を塩化メチレンで抽出（３回）した。有機層を合わせ飽
和食塩水で洗浄し、無水硫酸ナトリウムで乾燥後溶媒を
留去した。残留物をシリカゲルカラムクロマトグラフィ
ーに付し、ヘキサン−酢酸エチル（１９：１溶出液より
ピバリン酸フルフリルエステル3.2g（収率８６％）を得
た。1 H-NMR(δ,CDCl3):1.20(9H,s),5.05(2H,s),6.36(1H,dd,
J=1.8,3.3Hz),6.38(1,d,J=3.3Hz),7.41(1H,d,1.8Hz). IR(νcm-1,neat):2980,1810,1732,1484,1400,1368,128
2,1156,1016,962,924,746.Furfuryl alcohol 2 at 0 ° C. under nitrogen stream
25 mg of dimethylaminopyridine (0.2 mmo in 10 ml of anhydrous methylene chloride solution of g (20.4 mmol))
l) and triethylamine 4.3 ml (30.6 mmo
1) was added and the mixture was stirred as it was for 10 minutes. Next, 3.3 ml (26.5 mmol) of pivalic acid chloride was added dropwise to this solution, and the mixture was stirred at the same temperature for 30 minutes. After completion of the reaction, saturated aqueous ammonium chloride was added to the reaction mixture, the organic layer was separated, and the aqueous layer was extracted with methylene chloride (three times). The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated. The residue was subjected to silica gel column chromatography to obtain 3.2 g (yield 86%) of pivalic acid furfuryl ester from hexane-ethyl acetate (19: 1 eluate. 1 H-NMR (δ, CDCl 3 ): 1.20 (9H, s), 5.05 (2H, s), 6.36 (1H, dd,
J = 1.8,3.3Hz), 6.38 (1, d, J = 3.3Hz), 7.41 (1H, d, 1.8Hz) .IR (νcm -1 , neat): 2980,1810,1732,1484,1400,1368 , 128
2,1156,1016,962,924,746.
【００２８】（参考例４） フルフリル炭酸エチルReference Example 4 Furfuryl ethyl carbonate
【００２９】[0029]
【化１０】 [Chemical 10]
【００３０】窒素気流下０℃でフルフリルアルコ−ル２
ｇ（２０．４ｍｍｏｌ) の無水塩化メチレン１０ｍｌ溶
液にジメチルアミノピリジン２５ｍｇ（０．２ｍｍｏ
ｌ）とトリエチルアミン４．３ｍｌ（３０．６ｍｍｏ
ｌ）を加え、そのまま１０分撹拌した。次いでこの溶液
に塩化炭酸エチル２．５ｍｌ（２６．５ｍｍｏｌ）を滴
下し、同温で３０分撹拌した。反応終了後、反応混液に
飽和塩化アンモニウム水を加え有機層を分取し、水層を
塩化メチレンで抽出（３回）した。有機層を合わせ飽和
食塩水で洗浄し、無水硫酸ナトリウムで乾燥後溶媒を留
去した。残留物をシリカゲルカラムクロマトグラフィー
に付し、ヘキサン−酢酸エチル（１９：１）溶出液より
フルフリル炭酸エチル１．４８ｇ（収率４３％）を得
た。1 H-NMR(δ,CDCl3):1.31(3H,t,J=7.2Hz),4.22(2H,q,J=7.
2Hz),5.11(2H,s),6.36(1H,dd,J=1.8,3.2Hz),6.45(1H,d,
J=3.2Hz),7.43(1H,d,J=1.8Hz). IR(νcm-1,neat):2988,1756,1506,1448,1378,1250,115
4,1008,924,874,792,750Furfuryl alcohol 2 at 0 ° C. under a nitrogen stream.
25 mg of dimethylaminopyridine (0.2 mmo in 10 ml of anhydrous methylene chloride solution of g (20.4 mmol))
l) and triethylamine 4.3 ml (30.6 mmo
1) was added and the mixture was stirred as it was for 10 minutes. Next, 2.5 ml (26.5 mmol) of ethyl chloride carbonate was added dropwise to this solution, and the mixture was stirred at the same temperature for 30 minutes. After completion of the reaction, saturated aqueous ammonium chloride was added to the reaction mixture, the organic layer was separated, and the aqueous layer was extracted with methylene chloride (three times). The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated. The residue was subjected to silica gel column chromatography, and 1.48 g (yield 43%) of ethyl furfuryl carbonate was obtained from an eluent of hexane-ethyl acetate (19: 1). 1 H-NMR (δ, CDCl 3 ): 1.31 (3H, t, J = 7.2Hz), 4.22 (2H, q, J = 7.
2Hz), 5.11 (2H, s), 6.36 (1H, dd, J = 1.8,3.2Hz), 6.45 (1H, d,
J = 3.2Hz), 7.43 (1H, d, J = 1.8Hz) .IR (νcm -1 ,, neat): 2988,1756,1506,1448,1378,1250,115
4,1008,924,874,792,750
【００３１】（実施例１） ２−（フルフリルチオ）酢酸(Example 1) 2- (furfurylthio) acetic acid
【００３２】[0032]
【化１１】 [Chemical 11]
【００３３】窒素気流下チオグリコール酸１ｇ（１０．
９ｍｍｏｌ) とフルフリルアルコール１．６ｇ（１６．
３ｍｍｏｌ) の無水トルエン30ml溶液に、室温でトリフ
ルオロメタンスルホン酸亜鉛４０ｍｇ（０．１１ｍｍｏ
ｌ) を加え、その後３０分間加熱還流した。反応終了
後、反応混液に水を加え有機層を分取し、水層を酢酸エ
チルで抽出（３回）した。有機層を合わせ飽和食塩水で
洗浄し、無水硫酸ナトリウムで乾燥後溶媒を留去した。
残留物をシリカゲルカラムクロマトグラフィーに付し、
ヘキサン−酢酸エチル（３：２）溶出液より２−（フル
フリルチオ）酢酸１．２ｇ（収率６４％）を得た。1 H-NMR(δ,CDCl3):3.22(2H,s),3.88(2H,s),6.25(1H,d,J
=3.1Hz),6.32(1H,dd,J=1.9,3.1Hz),7.39(1H,d,J=1.9H
z). IR(νcm-1,neat):3124,2976,2568,1710,1506,1422,129
8,1150,1070,1012,940,742.Thioglycolic acid 1 g (10.
9 mmol) and 1.6 g of furfuryl alcohol (16.
To a solution of 3 mmol) in 30 ml of anhydrous toluene, 40 mg of zinc trifluoromethanesulfonate (0.11 mmo) at room temperature.
1) was added, and the mixture was heated under reflux for 30 minutes. After completion of the reaction, water was added to the reaction mixture, the organic layer was separated, and the aqueous layer was extracted with ethyl acetate (three times). The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated.
The residue was subjected to silica gel column chromatography,
1.2 g (yield 64%) of 2- (furfurylthio) acetic acid was obtained from the eluate of hexane-ethyl acetate (3: 2). 1 H-NMR (δ, CDCl 3 ): 3.22 (2H, s), 3.88 (2H, s), 6.25 (1H, d, J
= 3.1Hz), 6.32 (1H, dd, J = 1.9,3.1Hz), 7.39 (1H, d, J = 1.9H
z) .IR (νcm -1 ,, neat): 3124,2976,2568,1710,1506,1422,129
8,1150,1070,1012,940,742.
【００３４】（実施例２） ２−（フルフリルチオ）酢酸(Example 2) 2- (furfurylthio) acetic acid
【００３５】[0035]
【化１２】 [Chemical 12]
【００３６】窒素気流下チオグリコール酸１０ｇ（０．
１１ｍｏｌ）と酢酸フルフリルエステル１８．３ｇ
（０．１３ｍｏｌ）の無水テトラヒドロフラン２５０ｍ
ｌ溶液に、室温でトリフルオロメタンスルホン酸亜鉛１
９３ｍｇ（０．５４ｍｍｏｌ）を加え、その後１０時間
加熱還流した。反応終了後、反応混液に水を加えテトラ
ヒドロフランを留去した。残留物を酢酸エチルで抽出
（３回）し、有機層を合わせ飽和食塩水で洗浄し、無水
硫酸ナトリウムで乾燥後溶媒を留去した。残留物をシリ
カゲルカラムクロマトグラフィーに付し、ヘキサン−酢
酸エチル（３：２）溶出液より２−（フルフリルチオ）
酢酸１５．０８ｇ（収率８１％）を得た。1 H-NMR(δ,CDCl3):3.22(2H,s),3.88(2H,s),6.25(1H,d,J
=3.1Hz),6.32(1H,dd,J=1.9,3.1Hz),7.39(1H,d,J=1.9H
z). IR(νcm-1,neat):3124,2976,2568,1710,1506,1422,129
8,1150,1070,1012,940,742.Thioglycolic acid 10 g (0.
11 mol) and acetic acid furfuryl ester 18.3 g
(0.13 mol) anhydrous tetrahydrofuran 250 m
1 solution of zinc trifluoromethanesulfonate 1 at room temperature
93 mg (0.54 mmol) was added, and the mixture was heated under reflux for 10 hours. After the reaction was completed, water was added to the reaction mixture and the tetrahydrofuran was distilled off. The residue was extracted with ethyl acetate (3 times), the organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated. The residue was subjected to silica gel column chromatography, and 2- (furfurylthio) was extracted from a hexane-ethyl acetate (3: 2) eluate.
Acetic acid (15.08 g, yield 81%) was obtained. 1 H-NMR (δ, CDCl 3 ): 3.22 (2H, s), 3.88 (2H, s), 6.25 (1H, d, J
= 3.1Hz), 6.32 (1H, dd, J = 1.9,3.1Hz), 7.39 (1H, d, J = 1.9H
z) .IR (νcm -1 ,, neat): 3124,2976,2568,1710,1506,1422,129
8,1150,1070,1012,940,742.
【００３７】（実施例３） ２−（フルフリルチオ）酢酸(Example 3) 2- (furfurylthio) acetic acid
【００３８】[0038]
【化１３】 [Chemical 13]
【００３９】窒素気流下チオグリコール酸２００ｍｇ
（２．２ｍｍｏｌ) と安息香酸フルフリルエステル５７
１ｍｇ（２．８ｍｍｏｌ) の無水トルエン20ml溶液に、
室温でトリフルオロメタンスルホン酸亜鉛７９ｍｇ
（０．２２ｍｍｏｌ) を加え、その後10時間同温で撹拌
した。反応終了後、反応混液に水を加え有機層を分取
し、水層を酢酸エチルで抽出（３回）した。有機層を合
わせ飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥後
溶媒を留去した。残留物をシリカゲルカラムクロマトグ
ラフィーに付し、ヘキサン−酢酸エチル（３：２）溶出
液より２−（フルフリルチオ）酢酸２１０ｍｇ（収率５
６％）を得た。1 H-NMR(δ,CDCl3):3.22(2H,s),3.88(2H,s),6.25(1H,d,J
=3.1Hz),6.32(1H,dd,J=1.9,3.1Hz),7.39(1H,d,J=1.9H
z). IR(νcm-1,neat):3124,2976,2568,1710,1506,1422,129
8,1150,1070,1012,940,742.Thioglycolic acid 200 mg under nitrogen stream
(2.2 mmol) and benzoic acid furfuryl ester 57
To a solution of 1 mg (2.8 mmol) in anhydrous toluene,
79 mg zinc trifluoromethanesulfonate at room temperature
(0.22 mmol) was added and then the mixture was stirred at the same temperature for 10 hours. After completion of the reaction, water was added to the reaction mixture, the organic layer was separated, and the aqueous layer was extracted with ethyl acetate (three times). The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated. The residue was subjected to silica gel column chromatography, and 210 mg of 2- (furfurylthio) acetic acid (yield 5 from a hexane-ethyl acetate (3: 2) eluate)
6%) was obtained. 1 H-NMR (δ, CDCl 3 ): 3.22 (2H, s), 3.88 (2H, s), 6.25 (1H, d, J
= 3.1Hz), 6.32 (1H, dd, J = 1.9,3.1Hz), 7.39 (1H, d, J = 1.9H
z) .IR (νcm -1 ,, neat): 3124,2976,2568,1710,1506,1422,129
8,1150,1070,1012,940,742.
【００４０】（実施例４） ２−（フルフリルチオ）酢酸(Example 4) 2- (furfurylthio) acetic acid
【００４１】[0041]
【化１４】 Embedded image
【００４２】窒素気流下チオグリコール酸２００ｍｇ
（２．２ｍｍｏｌ) と４−アニス酸フルフリルエステル
７５６ｍｇ（３．３ｍｍｏｌ) の無水トルエン５ｍｌ溶
液に、室温でトリフルオロメタンスルホン酸亜鉛７９ｍ
ｇ（０．２２ｍｍｏｌ) を加え、その後１０時間同温で
撹拌した。反応終了後、反応混液に水を加え有機層を分
取し、水層を酢酸エチルで抽出（３回）した。有機層を
合わせ飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥
後溶媒を留去した。残留物をシリカゲルカラムクロマト
グラフィーに付し、ヘキサン−酢酸エチル（３：２）溶
出液より２−（フルフリルチオ）酢酸１９８ｍｇ（収率
５３％）を得た。1 H-NMR(δ,CDCl3):3.22(2H,s),3.88(2H,s),6.25(1H,d,J
=3.1Hz),6.32(1H,dd,J=1.9,3.1Hz),7.39(1H,d,J=1.9H
z). IR(νcm-1,neat):3124,2976,2568,1710,1506,1422,129
8,1150,1070,1012,940,742.Thioglycolic acid 200 mg under nitrogen stream
(2.2 mmol) and 4-anisic acid furfuryl ester (756 mg, 3.3 mmol) in a solution of anhydrous toluene (5 ml) at room temperature, zinc trifluoromethanesulfonate (79 m)
g (0.22 mmol) was added, and then the mixture was stirred at the same temperature for 10 hours. After completion of the reaction, water was added to the reaction mixture, the organic layer was separated, and the aqueous layer was extracted with ethyl acetate (three times). The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated. The residue was subjected to silica gel column chromatography, and 198 mg (yield 53%) of 2- (furfurylthio) acetic acid was obtained from a hexane-ethyl acetate (3: 2) eluate. 1 H-NMR (δ, CDCl 3 ): 3.22 (2H, s), 3.88 (2H, s), 6.25 (1H, d, J
= 3.1Hz), 6.32 (1H, dd, J = 1.9,3.1Hz), 7.39 (1H, d, J = 1.9H
z) .IR (νcm -1 ,, neat): 3124,2976,2568,1710,1506,1422,129
8,1150,1070,1012,940,742.
【００４３】（実施例５） ２−（フルフリルチオ）酢酸(Example 5) 2- (furfurylthio) acetic acid
【００４４】[0044]
【化１５】 [Chemical 15]
【００４５】窒素気流下チオグリコール酸２００ｍｇ
（２．２ｍｍｏｌ) と４−ニトロ安息香酸フルフリルエ
ステル８０５ｍｇ（３．３ｍｍｏｌ) の無水トルエン５
ｍｌ溶液に、室温でトリフルオロメタンスルホン酸亜鉛
７９ｍｇ（０．２２ｍｍｏｌ)を加え、その後１０時間
同温で撹拌した。反応終了後、反応混液に水を加え有機
層を分取し、水層を酢酸エチルで抽出（３回）した。有
機層を合わせ飽和食塩水で洗浄し、無水硫酸ナトリウム
で乾燥後溶媒を留去した。残留物をシリカゲルカラムク
ロマトグラフィーに付し、ヘキサン−酢酸エチル（３：
２）溶出液より２−（フルフリルチオ）酢酸１６０ｍｇ
（収率４３％）を得た。1 H-NMR(δ,CDCl3):3.22(2H,s),3.88(2H,s),6.25(1H,d,J
=3.1Hz),6.32(1H,dd,J=1.9,3.1Hz),7.39(1H,d,J=1.9H
z). IR(νcm-1,neat):3124,2976,2568,1710,1506,1422,129
8,1150,1070,1012,940,742.200 mg of thioglycolic acid under a nitrogen stream
(2.2 mmol) and 4-nitrobenzoic acid furfuryl ester 805 mg (3.3 mmol) anhydrous toluene 5
To the ml solution, 79 mg (0.22 mmol) of zinc trifluoromethanesulfonate was added at room temperature, and then the mixture was stirred at the same temperature for 10 hours. After completion of the reaction, water was added to the reaction mixture, the organic layer was separated, and the aqueous layer was extracted with ethyl acetate (three times). The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated. The residue was subjected to silica gel column chromatography, and hexane-ethyl acetate (3:
2) From the eluate, 160 mg of 2- (furfurylthio) acetic acid
(Yield 43%) was obtained. 1 H-NMR (δ, CDCl 3 ): 3.22 (2H, s), 3.88 (2H, s), 6.25 (1H, d, J
= 3.1Hz), 6.32 (1H, dd, J = 1.9,3.1Hz), 7.39 (1H, d, J = 1.9H
z) .IR (νcm -1 ,, neat): 3124,2976,2568,1710,1506,1422,129
8,1150,1070,1012,940,742.
【００４６】（実施例６） ２−（フルフリルチオ）酢酸(Example 6) 2- (furfurylthio) acetic acid
【００４７】[0047]
【化１６】 Embedded image
【００４８】窒素気流下チオグリコール酸２００ｍｇ
（２．２ｍｍｏｌ) と４−メトキシカルボニル安息香酸
フルフリルエステル８４８ｇ（３．３ｍｍｏｌ) の無水
トルエン５ｍｌ溶液に、室温でトリフルオロメタンスル
ホン酸亜鉛７９ｍｇ（０．２２ｍｍｏｌ) を加え、その
後２時間５０℃で撹拌した。反応終了後、反応混液に水
を加え有機層を分取し、水層を酢酸エチルで抽出（３
回）した。有機層を合わせ飽和食塩水で洗浄し、無水硫
酸ナトリウムで乾燥後溶媒を留去した。残留物をシリカ
ゲルカラムクロマトグラフィーに付し、ヘキサン−酢酸
エチル（３：２）溶出液より２−（フルフリルチオ）酢
酸１３０ｍｇ（収率３５％）を得た。1 H-NMR(δ,CDCl3):3.22(2H,s),3.88(2H,s),6.25(1H,d,J
=3.1Hz),6.32(1H,dd,J=1.9,3.1Hz),7.39(1H,d,J=1.9H
z). IR(νcm-1,neat):3124,2976,2568,1710,1506,1422,129
8,1150,1070,1012,940,742.200 mg of thioglycolic acid under a nitrogen stream
79 mg (0.22 mmol) of zinc trifluoromethanesulfonate was added at room temperature to a solution of (2.2 mmol) and 848 g (3.3 mmol) of furfuryl ester of 4-methoxycarbonylbenzoic acid in 5 ml of anhydrous toluene, and then at 50 ° C. for 2 hours. It was stirred. After completion of the reaction, water was added to the reaction mixture to separate the organic layer, and the aqueous layer was extracted with ethyl acetate (3
Times) The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated. The residue was subjected to silica gel column chromatography, and 130 mg (yield 35%) of 2- (furfurylthio) acetic acid was obtained from the eluent of hexane-ethyl acetate (3: 2). 1 H-NMR (δ, CDCl 3 ): 3.22 (2H, s), 3.88 (2H, s), 6.25 (1H, d, J
= 3.1Hz), 6.32 (1H, dd, J = 1.9,3.1Hz), 7.39 (1H, d, J = 1.9H
z) .IR (νcm -1 ,, neat): 3124,2976,2568,1710,1506,1422,129
8,1150,1070,1012,940,742.
【００４９】（実施例７） ２−（フルフリルチオ）酢酸Example 7 2- (furfurylthio) acetic acid
【００５０】[0050]
【化１７】 [Chemical 17]
【００５１】窒素気流下チオグリコール酸２００ｍｇ
（２．２ｍｍｏｌ) とピバリン酸フルフリルエステル５
９３ｍｇ（３．３ｍｍｏｌ) の無水トルエン５ｍｌ溶液
に、室温でトリフルオロメタンスルホン酸亜鉛７９ｍｇ
（０．２２ｍｍｏｌ) を加え、その後２時間５０℃で撹
拌した。反応終了後、反応混液に水を加え有機層を分取
し、水層を酢酸エチルで抽出（３回）した。有機層を合
わせ飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥後
溶媒を留去した。残留物をシリカゲルカラムクロマトグ
ラフィーに付し、ヘキサン−酢酸エチル（３：２）溶出
液より２−（フルフリルチオ）酢酸１２０ｍｇ（収率３
２％）を得た。1 H-NMR(δ,CDCl3):3.22(2H,s),3.88(2H,s),6.25(1H,d,J
=3.1Hz),6.32(1H,dd,J=1.9,3.1Hz),7.39(1H,d,J=1.9H
z). IR(νcm-1,neat):3124,2976,2568,1710,1506,1422,129
8,1150,1070,1012,940,742.Thioglycolic acid 200 mg under nitrogen stream
(2.2 mmol) and furfuryl pivalate 5
To a solution of 93 mg (3.3 mmol) in 5 ml of anhydrous toluene, 79 mg of zinc trifluoromethanesulfonate at room temperature
(0.22 mmol) was added and then stirred at 50 ° C. for 2 hours. After completion of the reaction, water was added to the reaction mixture, the organic layer was separated, and the aqueous layer was extracted with ethyl acetate (three times). The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated. The residue was subjected to silica gel column chromatography, and 120 mg of 2- (furfurylthio) acetic acid (yield 3 from a hexane-ethyl acetate (3: 2) eluate)
2%) was obtained. 1 H-NMR (δ, CDCl 3 ): 3.22 (2H, s), 3.88 (2H, s), 6.25 (1H, d, J
= 3.1Hz), 6.32 (1H, dd, J = 1.9,3.1Hz), 7.39 (1H, d, J = 1.9H
z) .IR (νcm -1 ,, neat): 3124,2976,2568,1710,1506,1422,129
8,1150,1070,1012,940,742.
【００５２】（実施例８） ２−（フルフリルチオ）酢酸Example 8 2- (Furfurylthio) acetic acid
【００５３】[0053]
【化１８】 Embedded image
【００５４】窒素気流下チオグリコール酸２００ｇ
（２．２ｍｍｏｌ) とフルフリル炭酸エチル５５４ｍｇ
（３．３ｍｍｏｌ) の無水トルエン５ｍｌ溶液に、室温
でトリフルオロメタンスルホン酸亜鉛７９ｍｇ（０．２
２ｍｍｏｌ) を加え、その後２時間５０℃で撹拌した。
反応終了後、反応混液に水を加え有機層を分取し、水層
を酢酸エチルで抽出（３回）した。有機層を合わせ飽和
食塩水で洗浄し、無水硫酸ナトリウムで乾燥後溶媒を留
去した。残留物をシリカゲルカラムクロマトグラフィー
に付し、ヘキサン−酢酸エチル（３：２）溶出液より２
−（フルフリルチオ）酢酸１５９ｍｇ（収率４３％）を
得た。1 H-NMR(δ,CDCl3):3.22(2H,s),3.88(2H,s),6.25(1H,d,J
=3.1Hz),6.32(1H,dd,J=1.9,3.1Hz),7.39(1H,d,J=1.9H
z). IR(νcm-1,neat):3124,2976,2568,1710,1506,1422,129
8,1150,1070,1012,940,742.200 g of thioglycolic acid under nitrogen stream
(2.2mmol) and furfuryl ethyl carbonate 554mg
To a solution of (3.3 mmol) in 5 ml of anhydrous toluene, 79 mg of zinc trifluoromethanesulfonate (0.2
2 mmol) was added, and the mixture was stirred at 50 ° C. for 2 hours.
After completion of the reaction, water was added to the reaction mixture, the organic layer was separated, and the aqueous layer was extracted with ethyl acetate (three times). The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated. The residue was subjected to silica gel column chromatography, and extracted with hexane-ethyl acetate (3: 2) eluate to give 2
159 mg (yield 43%) of-(furfurylthio) acetic acid was obtained. 1 H-NMR (δ, CDCl 3 ): 3.22 (2H, s), 3.88 (2H, s), 6.25 (1H, d, J
= 3.1Hz), 6.32 (1H, dd, J = 1.9,3.1Hz), 7.39 (1H, d, J = 1.9H
z) .IR (νcm -1 ,, neat): 3124,2976,2568,1710,1506,1422,129
8,1150,1070,1012,940,742.
【００５５】（実施例９） ２−（フルフリルチオ）酢酸Example 9 2- (furfurylthio) acetic acid
【００５６】[0056]
【化１９】 [Chemical 19]
【００５７】窒素気流下チオグリコール酸５００ｍｇ
（５．４ｍｍｏｌ) とフルフリルメチルエーテル７９１
ｍｇ（７．１ｍｍｏｌ) の無水テトラヒドロフラン１５
ｍｌ溶液に、室温でトリフルオロメタンスルホン酸亜鉛
４０ｍｇ（０．１１ｍｍｏｌ)を加え、その後１０時間
加熱還流した。反応終了後、反応混液に水を加え有機層
を分取し、水層を酢酸エチルで抽出（３回）した。有機
層を合わせ飽和食塩水で洗浄し、無水硫酸ナトリウムで
乾燥後溶媒を留去した。残留物をシリカゲルカラムクロ
マトグラフィーに付し、ヘキサン−酢酸エチル（３：
２）溶出液より２−（フルフリルチオ）酢酸３５５ｍｇ
（収率３８％）を得た。1 H-NMR(δ,CDCl3):3.22(2H,s),3.88(2H,s),6.25(1H,d,J
=3.1Hz),6.32(1H,dd,J=1.9,3.1Hz),7.39(1H,d,J=1.9H
z). IR(νcm-1,neat):3124,2976,2568,1710,1506,1422,129
8,1150,1070,1012,940,742.Thioglycolic acid 500 mg under nitrogen stream
(5.4 mmol) and furfuryl methyl ether 791
mg (7.1 mmol) of anhydrous tetrahydrofuran 15
40 mg (0.11 mmol) of zinc trifluoromethanesulfonate was added to the ml solution at room temperature, and the mixture was heated under reflux for 10 hours. After completion of the reaction, water was added to the reaction mixture, the organic layer was separated, and the aqueous layer was extracted with ethyl acetate (three times). The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated. The residue was subjected to silica gel column chromatography, and hexane-ethyl acetate (3:
2) From the eluate, 2- (furfurylthio) acetic acid 355 mg
(38% yield). 1 H-NMR (δ, CDCl 3 ): 3.22 (2H, s), 3.88 (2H, s), 6.25 (1H, d, J
= 3.1Hz), 6.32 (1H, dd, J = 1.9,3.1Hz), 7.39 (1H, d, J = 1.9H
z) .IR (νcm -1 ,, neat): 3124,2976,2568,1710,1506,1422,129
8,1150,1070,1012,940,742.
【００５８】（実施例１０） ２−（フルフリルチオ）酢酸Example 10 2- (Furfurylthio) acetic acid
【００５９】[0059]
【化２０】 Embedded image
【００６０】窒素気流下チオグリコール酸２００ｍｇ
（２．２ｍｍｏｌ) と酢酸フルフリルエステル３９６ｍ
ｇ（２．８ｍｍｏｌ) の無水トルエン５ｍｌ溶液に、室
温で塩化亜鉛３０ｍｇ（０．２２ｍｍｏｌ) を加え、そ
の後８０℃に加熱し３時間撹拌した。反応終了後、反応
混液に水を加え有機層を分取し、水層を酢酸エチルで抽
出（３回）した。有機層を合わせ飽和食塩水で洗浄し、
無水硫酸ナトリウムで乾燥後溶媒を留去した。残留物を
シリカゲルカラムクロマトグラフィーに付し、ヘキサン
−酢酸エチル（３：２）溶出液より２−（フルフリルチ
オ）酢酸２１０ｍｇ（収率５６％）を得た。1 H-NMR(δ,CDCl3):3.22(2H,s),3.88(2H,s),6.25(1H,d,J
=3.1Hz),6.32(1H,dd,J=1.9,3.1Hz),7.39(1H,d,J=1.9H
z). IR(νcm-1,neat):3124,2976,2568,1710,1506,1422,129
8,1150,1070,1012,940,742.Thioglycolic acid 200 mg under nitrogen stream
(2.2 mmol) and furfuryl acetate 396m
To a solution of g (2.8 mmol) in anhydrous toluene (5 ml) was added zinc chloride (30 mg, 0.22 mmol) at room temperature, and then the mixture was heated to 80 ° C. and stirred for 3 hours. After completion of the reaction, water was added to the reaction mixture, the organic layer was separated, and the aqueous layer was extracted with ethyl acetate (three times). The organic layers were combined and washed with saturated saline,
After drying over anhydrous sodium sulfate, the solvent was distilled off. The residue was subjected to silica gel column chromatography, and 210 mg (yield 56%) of 2- (furfurylthio) acetic acid was obtained from the eluent of hexane-ethyl acetate (3: 2). 1 H-NMR (δ, CDCl 3 ): 3.22 (2H, s), 3.88 (2H, s), 6.25 (1H, d, J
= 3.1Hz), 6.32 (1H, dd, J = 1.9,3.1Hz), 7.39 (1H, d, J = 1.9H
z) .IR (νcm -1 ,, neat): 3124,2976,2568,1710,1506,1422,129
8,1150,1070,1012,940,742.
【００６１】（実施例１１） ２−（フルフリルチオ）酢酸(Example 11) 2- (furfurylthio) acetic acid
【００６２】[0062]
【化２１】 [Chemical 21]
【００６３】窒素気流下チオグリコール酸２００ｍｇ
（２．２ｍｍｏｌ) と酢酸フルフリルエステル３９６ｍ
ｇ（２．８ｍｍｏｌ) の無水トルエン５ｍｌ溶解液に、
室温でヨウ化亜鉛６９ｍｇ（０．２２ｍｍｏｌ) を加
え、その後８０℃に加熱し２時間撹拌した。反応終了
後、反応混液に水を加え有機層を分取し、水層を酢酸エ
チルで抽出（３回）した。有機層を合わせ飽和食塩水で
洗浄し、無水硫酸ナトリウムで乾燥後溶媒を留去した。
残留物をシリカゲルカラムクロマトグラフィーに付し、
ヘキサン−酢酸エチル（３：２）溶出液より２−（フル
フリルチオ）酢酸２００ｍｇ（収率５４％）を得た。1 H-NMR(δ,CDCl3):3.22(2H,s),3.88(2H,s),6.25(1H,d,J
=3.1Hz),6.32(1H,dd,J=1.9,3.1Hz),7.39(1H,d,J=1.9H
z). IR(νcm-1,neat):3124,2976,2568,1710,1506,1422,129
8,1150,1070,1012,940,742.Thioglycolic acid 200 mg under nitrogen stream
(2.2 mmol) and furfuryl acetate 396m
g (2.8 mmol) in a solution of anhydrous toluene 5 ml,
69 mg (0.22 mmol) of zinc iodide was added at room temperature, then heated to 80 ° C. and stirred for 2 hours. After completion of the reaction, water was added to the reaction mixture, the organic layer was separated, and the aqueous layer was extracted with ethyl acetate (three times). The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated.
The residue was subjected to silica gel column chromatography,
200 mg (54% yield) of 2- (furfurylthio) acetic acid was obtained from the eluate of hexane-ethyl acetate (3: 2). 1 H-NMR (δ, CDCl 3 ): 3.22 (2H, s), 3.88 (2H, s), 6.25 (1H, d, J
= 3.1Hz), 6.32 (1H, dd, J = 1.9,3.1Hz), 7.39 (1H, d, J = 1.9H
z) .IR (νcm -1 ,, neat): 3124,2976,2568,1710,1506,1422,129
8,1150,1070,1012,940,742.
【００６４】（実施例１２） ２−（フルフリルチオ）酢酸(Example 12) 2- (furfurylthio) acetic acid
【００６５】[0065]
【化２２】 [Chemical formula 22]
【００６６】窒素気流下チオグリコール酸２００ｍｇ
（２．２ｍｍｏｌ) と酢酸フルフリルエステル４５６ｍ
ｇ（３．３ｍｍｏｌ) の無水トルエン５ｍｌ溶液に、室
温でトリフルオロボラン・ジエチルエーテル錯体０．０
３ｍｌ（０．２２ｍｍｏｌ) を加え、同温で１０時間撹
拌した。反応終了後、反応混液に水を加え有機層を分取
し、水層を酢酸エチルで抽出（３回）した。有機層を合
わせ飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥後
溶媒を留去した。残留物をシリカゲルカラムクロマトグ
ラフィーに付し、ヘキサン−酢酸エチル（３：２）溶出
液より２−（フルフリルチオ）酢酸１７９ｍｇ（収率４
８％）を得た。1 H-NMR(δ,CDCl3):3.22(2H,s),3.88(2H,s),6.25(1H,d,J
=3.1Hz),6.32(1H,dd,J=1.9,3.1Hz),7.39(1H,d,J=1.9H
z). IR(νcm-1,neat):3124,2976,2568,1710,1506,1422,129
8,1150,1070,1012,940,742.Thioglycolic acid 200 mg under nitrogen stream
(2.2mmol) and acetic acid furfuryl ester 456m
To a solution of g (3.3 mmol) in 5 ml of anhydrous toluene, at room temperature, trifluoroborane-diethyl ether complex 0.0
3 ml (0.22 mmol) was added, and the mixture was stirred at the same temperature for 10 hours. After completion of the reaction, water was added to the reaction mixture, the organic layer was separated, and the aqueous layer was extracted with ethyl acetate (three times). The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated. The residue was subjected to silica gel column chromatography, and 179 mg of 2- (furfurylthio) acetic acid was obtained from a hexane-ethyl acetate (3: 2) eluate (yield 4
8%). 1 H-NMR (δ, CDCl 3 ): 3.22 (2H, s), 3.88 (2H, s), 6.25 (1H, d, J
= 3.1Hz), 6.32 (1H, dd, J = 1.9,3.1Hz), 7.39 (1H, d, J = 1.9H
z) .IR (νcm -1 ,, neat): 3124,2976,2568,1710,1506,1422,129
8,1150,1070,1012,940,742.
【００６７】（実施例１３） ２−（フルフリルチオ）酢酸(Example 13) 2- (furfurylthio) acetic acid
【００６８】[0068]
【化２３】 [Chemical formula 23]
【００６９】窒素気流下チオグリコール酸２００ｍｇ
（２．２ｍｍｏｌ) と酢酸フルフリルエステル４５６ｍ
ｇ（３．３ｍｍｏｌ) の無水アセトニトリル５ｍｌ溶液
に、室温でリチウムテトラフルオロボレート２０ｍｇ
（０．２２ｍｍｏｌ) を加え、その後３時間加熱還流し
た。反応終了後、反応混液に水を加えアセトニトリルを
留去した。残留物を酢酸エチルで抽出（３回）し、有機
層を飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥後
溶媒を留去した。残留物をシリカゲルカラムクロマトグ
ラフィーに付し、ヘキサン−酢酸エチル（３：２）溶出
液より２−（フルフリルチオ）酢酸１８０ｍｇ（収率４
８％）を得た。1 H-NMR(δ,CDCl3):3.22(2H,s),3.88(2H,s),6.25(1H,d,J
=3.1Hz),6.32(1H,dd,J=1.9,3.1Hz),7.39(1H,d,J=1.9H
z). IR(νcm-1,neat):3124,2976,2568,1710,1506,1422,129
8,1150,1070,1012,940,742.Thioglycolic acid 200 mg under nitrogen stream
(2.2mmol) and acetic acid furfuryl ester 456m
20 mg of lithium tetrafluoroborate at room temperature in 5 ml of anhydrous acetonitrile containing g (3.3 mmol).
(0.22 mmol) was added, and the mixture was heated under reflux for 3 hours. After completion of the reaction, water was added to the reaction mixture and acetonitrile was distilled off. The residue was extracted with ethyl acetate (three times), the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated. The residue was subjected to silica gel column chromatography, and 180 mg of 2- (furfurylthio) acetic acid (yield 4 from a hexane-ethyl acetate (3: 2) eluate)
8%). 1 H-NMR (δ, CDCl 3 ): 3.22 (2H, s), 3.88 (2H, s), 6.25 (1H, d, J
= 3.1Hz), 6.32 (1H, dd, J = 1.9,3.1Hz), 7.39 (1H, d, J = 1.9H
z) .IR (νcm -1 ,, neat): 3124,2976,2568,1710,1506,1422,129
8,1150,1070,1012,940,742.
【００７０】（実施例１４） ２−（フルフリルチオ）酢酸(Example 14) 2- (furfurylthio) acetic acid
【００７１】[0071]
【化２４】 [Chemical formula 24]
【００７２】窒素気流下チオグリコール酸２００ｍｇ
（２．２ｍｍｏｌ) と酢酸フルフリルエステル４５６ｍ
ｇ（３．３ｍｍｏｌ) の無水トルエン５ｍｌ溶液に、室
温で過塩素酸リチウム２３ｍｇ（０．２２ｍｍｏｌ) を
加え、その後８０℃に加熱し１時間撹拌した。反応終了
後、反応混液に水を加えアセトニトリルを留去した。残
留物を酢酸エチルで抽出（３回）し、有機層を飽和食塩
水で洗浄し、無水硫酸ナトリウムで乾燥後溶媒を留去し
た。残留物をシリカゲルカラムクロマトグラフィーに付
し、ヘキサン−酢酸エチル（３：２）溶出液より２−
（フルフリルチオ）酢酸１９０ｍｇ（収率５１％）を得
た。1 H-NMR(δ,CDCl3):3.22(2H,s),3.88(2H,s),6.25(1H,d,J
=3.1Hz),6.32(1H,dd,J=1.9,3.1Hz),7.39(1H,d,J=1.9H
z). IR(νcm-1,neat):3124,2976,2568,1710,1506,1422,129
8,1150,1070,1012,940,742.Thioglycolic acid 200 mg under nitrogen stream
(2.2mmol) and acetic acid furfuryl ester 456m
23 mg (0.22 mmol) of lithium perchlorate was added to a solution of g (3.3 mmol) in 5 ml of anhydrous toluene at room temperature and then heated to 80 ° C. and stirred for 1 hour. After completion of the reaction, water was added to the reaction mixture and acetonitrile was distilled off. The residue was extracted with ethyl acetate (three times), the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated. The residue was subjected to silica gel column chromatography, and extracted with hexane-ethyl acetate (3: 2) eluate to give 2-
190 mg (yield 51%) of (furfurylthio) acetic acid was obtained. 1 H-NMR (δ, CDCl 3 ): 3.22 (2H, s), 3.88 (2H, s), 6.25 (1H, d, J
= 3.1Hz), 6.32 (1H, dd, J = 1.9,3.1Hz), 7.39 (1H, d, J = 1.9H
z) .IR (νcm -1 ,, neat): 3124,2976,2568,1710,1506,1422,129
8,1150,1070,1012,940,742.
【００７３】（実施例１５） ２−（フルフリルチオ）酢酸(Example 15) 2- (furfurylthio) acetic acid
【００７４】[0074]
【化２５】 [Chemical 25]
【００７５】窒素気流下チオグリコール酸２００ｍｇ
（２．２ｍｍｏｌ) と酢酸フルフリルエステル４５６ｍ
ｇ（３．３ｍｍｏｌ) の無水トルエン５ｍｌ溶液に、室
温でジエチル塩化アルミニウム０．２２ｍｌ（１．０ｍ
ｏｌ／１ヘキサン溶液）を加え、その後１０時間加熱還
流した。反応終了後、反応混液に水を加え有機層を分取
し、水層を酢酸エチルで抽出（３回）した。有機層を合
わせ飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥後
溶媒を留去した。残留物をシリカゲルカラムクロマトグ
ラフィーに付し、ヘキサン−酢酸エチル（３：２）溶出
液より２−（フルフリルチオ）酢酸２００ｍｇ（収率５
３％）を得た。1 H-NMR(δ,CDCl3):3.22(2H,s),3.88(2H,s),6.25(1H,d,J
=3.1Hz),6.32(1H,dd,J=1.9,3.1Hz),7.39(1H,d,J=1.9H
z). IR(νcm-1,neat):3124,2976,2568,1710,1506,1422,129
8,1150,1070,1012,940,742.Thioglycolic acid 200 mg under nitrogen stream
(2.2mmol) and acetic acid furfuryl ester 456m
To a solution of g (3.3 mmol) in 5 ml of anhydrous toluene, at room temperature, 0.22 ml of diethyl aluminum chloride (1.0 m
(ol / 1 hexane solution) was added, and the mixture was heated under reflux for 10 hours. After completion of the reaction, water was added to the reaction mixture, the organic layer was separated, and the aqueous layer was extracted with ethyl acetate (three times). The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated. The residue was subjected to silica gel column chromatography, and 200 mg of 2- (furfurylthio) acetic acid (yield 5
3%). 1 H-NMR (δ, CDCl 3 ): 3.22 (2H, s), 3.88 (2H, s), 6.25 (1H, d, J
= 3.1Hz), 6.32 (1H, dd, J = 1.9,3.1Hz), 7.39 (1H, d, J = 1.9H
z) .IR (νcm -1 ,, neat): 3124,2976,2568,1710,1506,1422,129
8,1150,1070,1012,940,742.
【００７６】（実施例１６） ２−（フルフリルチオ）酢酸(Example 16) 2- (furfurylthio) acetic acid
【００７７】[0077]
【化２６】 [Chemical formula 26]
【００７８】窒素気流下チオグリコール酸２００ｍｇ
（２．２ｍｍｏｌ) と酢酸フルフリルエステル４５６ｍ
ｇ（３．３ｍｍｏｌ) の無水トルエン５ｍｌ溶液に、室
温でメチル塩化アルミニウム０．２２ｍｌ（１．０ｍｏ
ｌ／１ヘキサン溶液）を加え、その後５時間加熱還流し
た。反応終了後、反応混液に水を加え有機層を分取し、
水層を酢酸エチルで抽出（３回）した。有機層を合わせ
飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥後溶媒
を留去した。残留物をシリカゲルカラムクロマトグラフ
ィーに付し、ヘキサン−酢酸エチル（３：２）溶出液よ
り２−（フルフリルチオ）酢酸２３６ｍｇ（収率７０
％）を得た。1 H-NMR(δ,CDCl3):3.22(2H,s),3.88(2H,s),6.25(1H,d,J
=3.1Hz),6.32(1H,dd,J=1.9,3.1Hz),7.39(1H,d,J=1.9H
z). IR(νcm-1,neat):3124,2976,2568,1710,1506,1422,129
8,1150,1070,1012,940,742.Thioglycolic acid 200 mg under nitrogen stream
(2.2mmol) and acetic acid furfuryl ester 456m
To a solution of g (3.3 mmol) in 5 ml of anhydrous toluene, 0.22 ml of methyl aluminum chloride (1.0 mo
(1/1 hexane solution) was added, and the mixture was heated under reflux for 5 hours. After the reaction was completed, water was added to the reaction mixture to separate the organic layer,
The aqueous layer was extracted with ethyl acetate (3 times). The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated. The residue was subjected to silica gel column chromatography, and 236 mg of 2- (furfurylthio) acetic acid was obtained from a hexane-ethyl acetate (3: 2) eluate (yield 70
%) Was obtained. 1 H-NMR (δ, CDCl 3 ): 3.22 (2H, s), 3.88 (2H, s), 6.25 (1H, d, J
= 3.1Hz), 6.32 (1H, dd, J = 1.9,3.1Hz), 7.39 (1H, d, J = 1.9H
z) .IR (νcm -1 ,, neat): 3124,2976,2568,1710,1506,1422,129
8,1150,1070,1012,940,742.
【００７９】（実施例１７） ２−（フルフリルチオ）酢酸メチルエステルExample 17 2- (Furfurylthio) acetic acid methyl ester
【００８０】[0080]
【化２７】 [Chemical 27]
【００８１】窒素気流下チオグリコール酸メチルエステ
ル５００ｍｇ（４．７ｍｍｏｌ) と酢酸フルフリルエス
テル８５８ｍｇ（６．１ｍｍｏｌ) の無水テトラヒドロ
フラン１５ｍｌ溶液に、室温でトリフルオロメタンスル
ホン酸亜鉛１７１ｍｇ（０．４７ｍｍｏｌ）を加え、そ
の後３時間加熱還流した。反応終了後、反応混液に水を
加え、テトラヒドロフラン留去した。残留物を酢酸エチ
ルで抽出（３回）した。有機層を合わせ飽和食塩水で洗
浄し、無水硫酸ナトリウムで乾燥後溶媒を留去した。残
留物をシリカゲルカラムクロマトグラフィーに付し、ヘ
キサン−酢酸エチル（４：１）溶出液より２−（フルフ
リルチオ）酢酸メチルエステル５００ｍｇ（収率５７
％）を得た。1 H-NMR(δ,CDCL3):3.20(2H,s),3.74(3H,s),3.86(2H,s),
6.23(1H,d,J=3.0Hz),6.32(1H,dd,J=1.9,3.0Hz),7.38(1
H,d,J=1.9Hz). IR(νcm-1,neat):2956,1744,1592,1506,1438,1412,128
0,1126,1070,1021,940,742,600.To a solution of 500 mg (4.7 mmol) of thioglycolic acid methyl ester and 858 mg (6.1 mmol) of furfuryl acetate acetate in 15 ml of anhydrous tetrahydrofuran under a nitrogen stream, 171 mg (0.47 mmol) of zinc trifluoromethanesulfonate was added at room temperature. Then, the mixture was heated under reflux for 3 hours. After completion of the reaction, water was added to the reaction mixture, and tetrahydrofuran was distilled off. The residue was extracted with ethyl acetate (3 times). The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated. The residue was subjected to silica gel column chromatography, and 500 mg of 2- (furfurylthio) acetic acid methyl ester was obtained from a hexane-ethyl acetate (4: 1) eluate (yield 57
%) Was obtained. 1 H-NMR (δ, CDCL 3 ): 3.20 (2H, s), 3.74 (3H, s), 3.86 (2H, s),
6.23 (1H, d, J = 3.0Hz), 6.32 (1H, dd, J = 1.9,3.0Hz), 7.38 (1
H, d, J = 1.9Hz) .IR (νcm -1 ,, neat): 2956,1744,1592,1506,1438,1412,128
0,1126,1070,1021,940,742,600.
【００８２】（実施例１８） フルフリルチオアセトアミドExample 18 Furfuryl thioacetamide
【００８３】[0083]
【化２８】 [Chemical 28]
【００８４】窒素気流下チオグリコール酸アミド５００
ｍｇ（５．５ｍｍｏｌ) と酢酸フルフリルエステル１ｇ
（７．１ｍｍｏｌ）の無水1,4-ジオキサン15ml溶液に、
室温でトリフルオロメタンスルホン酸亜鉛４０ｍｇ
（０．１１ｍｍｏｌ) を加え、その後５時間加熱環流し
た。反応終了後、反応混液に水を加えテトラヒドロフラ
ン留去した。残留物を酢酸エチルで抽出（３回）した。
有機層を合わせ飽和食塩水で洗浄し、無水硫酸ナトリウ
ムで乾燥後溶媒を留去した。残留物をシリカゲルカラム
クロマトグラフィーに付し、酢酸エチル−ヘキサン
（３：１）溶出液よりフルフリルチオアセトアミド６２
０ｍｇ（収率６７％）を得た。1 H-NMR(δ,CDCl3):3.21(2H,s).3.79(2H,s),5.38(1H,br-
s),6.23(1H,d,J=3.3Hz),6.32(1H,dd,J=1.9,3.3Hz),6.55
(1H,br-s),7.38(1H,d,J=1.9Hz). IR(νcm-1,KBr):3400,3280,1640,1505,1410,1400,1385,
1260,1225,1150,1005,940,745.Thioglycolamide 500 under nitrogen stream
mg (5.5 mmol) and acetic acid furfuryl ester 1 g
To a solution of (7.1 mmol) in anhydrous 1,4-dioxane (15 ml),
40 mg zinc trifluoromethanesulfonate at room temperature
(0.11 mmol) was added, and the mixture was heated to reflux for 5 hours. After completion of the reaction, water was added to the reaction mixture and the tetrahydrofuran was distilled off. The residue was extracted with ethyl acetate (3 times).
The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated. The residue was subjected to silica gel column chromatography, and furfurylthioacetamide 62 was obtained from the eluent of ethyl acetate-hexane (3: 1).
0 mg (yield 67%) was obtained. 1 H-NMR (δ, CDCl 3 ): 3.21 (2H, s) .3.79 (2H, s), 5.38 (1H, br-
s), 6.23 (1H, d, J = 3.3Hz), 6.32 (1H, dd, J = 1.9,3.3Hz), 6.55
(1H, br-s), 7.38 (1H, d, J = 1.9Hz) .IR (νcm -1 ,, KBr): 3400,3280,1640,1505,1410,1400,1385,
1260,1225,1150,1005,940,745.
【００８５】（実施例１９） ２−（３−フリルメチルチオ）酢酸(Example 19) 2- (3-furylmethylthio) acetic acid
【００８６】[0086]
【化２９】 [Chemical 29]
【００８７】窒素気流下チオグリコール酸５００ｍｇ
（５．４ｍｍｏｌ) と酢酸３−フリルメチルエステル９
９０ｍｇ（７．１ｍｍｏｌ) の無水テトラヒドロフラン
15ml溶液に、室温でトリフルオロメタンスルホン酸亜鉛
１９７ｍｇ（０．５４ｍｍｏｌ）を加え、その後１０時
間加熱還流した。反応終了後、反応混液に水を加えテト
ラヒドロフランを留去した。残留物を酢酸エチルで抽出
（３回）し、有機層を合わせ飽和食塩水で洗浄し、無水
硫酸ナトリウムで乾燥後溶媒を留去した。残留物をシリ
カゲルカラムクロマトグラフィーに付し、ヘキサン−酢
酸エチル（３：２）溶出液より２−（３−フリルメチル
チオ）酢酸４７０ｍｇ（収率５０％）を得た。1 H-NMR(δ,CDCl3):3.15(2H,s),3.71(2H,s),6.41(1H,s),
7.39-7.44(2H,m). IR(νcm-1,neat):3144,2928,1710,1506,1424,1296,116
6,1070,1022,874,792,734,686.Thioglycolic acid 500 mg under nitrogen stream
(5.4 mmol) and acetic acid 3-furyl methyl ester 9
90 mg (7.1 mmol) anhydrous tetrahydrofuran
To the 15 ml solution, zinc trifluoromethanesulfonate (197 mg, 0.54 mmol) was added at room temperature, and the mixture was heated under reflux for 10 hours. After the reaction was completed, water was added to the reaction mixture and the tetrahydrofuran was distilled off. The residue was extracted with ethyl acetate (three times), the organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated. The residue was subjected to silica gel column chromatography, and 470 mg of 2- (3-furylmethylthio) acetic acid (yield 50%) was obtained from a hexane-ethyl acetate (3: 2) eluate. 1 H-NMR (δ, CDCl 3 ): 3.15 (2H, s), 3.71 (2H, s), 6.41 (1H, s),
7.39-7.44 (2H, m) .IR (νcm -1 ,, neat): 3144,2928,1710,1506,1424,1296,116
6,1070,1022,874,792,734,686.
【００８８】（実施例２０） ２−（２−テニルチオ）酢酸Example 20 2- (2-Tenylthio) acetic acid
【００８９】[0089]
【化３０】 Embedded image
【００９０】窒素気流下チオグリコール酸１ｇ（１．０
９ｍｍｏｌ) と酢酸２−テニルエステル２．０３ｇ（１
３．０ｍｍｏｌ）の無水トルエン２５ｍｌ溶液に、室温
でトリフルオロメタンスルホン酸亜鉛３９５ｍｇ（１．
１ｍｍｏｌ) を加え、同温で１日撹拌した。反応終了
後、反応混液に水を加え有機層を分取し、水層を酢酸エ
チルで抽出（３回）した。有機層を合わせ飽和食塩水で
洗浄し、無水硫酸ナトリウムで乾燥後溶媒を留去した。
残留物をシリカゲルカラムクロマトグラフィーに付し、
ヘキサン−酢酸エチル（３：２）溶出液より２−（２−
テニルチオ）酢酸１．０８ｇ（収率５３％）を得た。1 H-NMR(δ,CDCl3):3.20(2H,s),4.10(2H,s),6.93(1H,dd,
J=3.5,5.1Hz),6.99(1H,dd,J=1.3,5.1Hz),7.25(1H,dd,J=
1.3,3.5Hz). IR(νcm-1,neat):3108,2916,1708,1424,1298,1254,120
0,1142,924,854,704.Thioglycolic acid 1 g (1.0
9 mmol) and 2.03 g of acetic acid 2-thenyl ester (1
A solution of 3.0 mmol) in 25 ml of anhydrous toluene was added at room temperature to 395 mg of zinc trifluoromethanesulfonate (1.
1 mmol) was added and the mixture was stirred at the same temperature for 1 day. After completion of the reaction, water was added to the reaction mixture, the organic layer was separated, and the aqueous layer was extracted with ethyl acetate (three times). The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated.
The residue was subjected to silica gel column chromatography,
From the eluate of hexane-ethyl acetate (3: 2), 2- (2-
1.08 g (yield 53%) of tenylthio) acetic acid was obtained. 1 H-NMR (δ, CDCl 3 ): 3.20 (2H, s), 4.10 (2H, s), 6.93 (1H, dd,
J = 3.5,5.1Hz), 6.99 (1H, dd, J = 1.3,5.1Hz), 7.25 (1H, dd, J =
IR (νcm -1 ,, neat): 3108,2916,1708,1424,1298,1254,120
0,1142,924,854,704.
【００９１】（実施例２１） ２−（３−テニルチオ）酢酸Example 21 2- (3-Tenylthio) acetic acid
【００９２】[0092]
【化３１】 [Chemical 31]
【００９３】窒素気流下チオグリコール酸５００ｍｇ
（５．４ｍｍｏｌ) と酢酸３−テニルエステル１．０２
ｇ（６．５ｍｍｏｌ) の無水トルエン２５ｍｌ溶液に、
室温でトリフルオロメタンスルホン酸亜鉛２００ｍｇ
（０．５４ｍｍｏｌ）を加え、同温で１日撹拌した。反
応終了後、反応混液に水を加え有機層を分取し、水層を
を酢酸エチルで抽出（３回）した。有機層を合わせ飽和
食塩水で洗浄し、無水硫酸ナトリウムで乾燥後溶媒を留
去した。残留物をシリカゲルカラムクロマトグラフィー
に付し、ヘキサン−酢酸エチル（３：２）溶出液より２
−（３−テニルチオ）酢酸５５０ｍｇ（収率５４％）を
得た。1 H-NMR(δ,CDCl3):3.12(2H,s),3.89(2H,s),7.08(1H,dd,
J=1.2,4.9Hz),7.18(1H,dd,J=1.2,3.0Hz),7.31(1H,dd,J=
3.0,4,9Hz). IR(νcm-1,neat):3104,2916,1716,1424,1298,1244,120
0,1156,946,920,836,786,708,678.Thioglycolic acid 500 mg under nitrogen stream
(5.4 mmol) and acetic acid 3-thenyl ester 1.02
g (6.5 mmol) in 25 ml of anhydrous toluene,
200 mg zinc trifluoromethanesulfonate at room temperature
(0.54 mmol) was added, and the mixture was stirred at the same temperature for 1 day. After completion of the reaction, water was added to the reaction mixture, the organic layer was separated, and the aqueous layer was extracted with ethyl acetate (three times). The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated. The residue was subjected to silica gel column chromatography, and extracted with hexane-ethyl acetate (3: 2) eluate to give 2
550 mg (yield 54%) of-(3-tenylthio) acetic acid was obtained. 1 H-NMR (δ, CDCl 3 ): 3.12 (2H, s), 3.89 (2H, s), 7.08 (1H, dd,
J = 1.2,4.9Hz), 7.18 (1H, dd, J = 1.2,3.0Hz), 7.31 (1H, dd, J =
3.0 (4,9Hz) .IR (νcm -1 , neat): 3104,2916,1716,1424,1298,1244,120
0,1156,946,920,836,786,708,678.
【００９４】（実施例２３） ２−（ベンジルチオ）酢酸(Example 23) 2- (benzylthio) acetic acid
【００９５】[0095]
【化３２】 Embedded image
【００９６】窒素気流下チオグリコール酸１ｇ（１０．
８ｍｍｏｌ) と酢酸ベンジルエステル１．９６ｇ（１
３．０ｍｍｏｌ）の無水トルエン２５ｍｌ溶液に、室温
でトリフルオロメタンスルホン酸亜鉛３．９５ｇ（１
０．８ｍｍｏｌ）を加え、その後２日間加熱還流した。
反応終了後、反応混液に水を加え有機層を分取し、水層
を酢酸エチルで抽出（３回）した。有機層を合わせ飽和
食塩水で洗浄し、無水硫酸ナトリウムで乾燥後溶媒を留
去した。残留物をシリカゲルカラムクロマトグラフィー
に付し、ヘキサン−酢酸エチル（３：２）溶出液より２
−（ベンジルチオ）酢酸４７３ｍｇ（収率２４％）を得
た。1 H-NMR(δ,CDCl3):3.11(2H,s),3.86(2H,s),7.23-7.37(5
H,m). IR(νcm-1,neat):3032,2920,1710,1496,1456,1424,130
0,1200,1132,930,768,702.Thioglycolic acid 1 g (10.
8 mmol) and 1.96 g of acetic acid benzyl ester (1
(3.0 mmol) in 25 ml of anhydrous toluene at room temperature, 3.95 g of zinc trifluoromethanesulfonate (1
0.8 mmol) was added, and the mixture was heated under reflux for 2 days.
After completion of the reaction, water was added to the reaction mixture, the organic layer was separated, and the aqueous layer was extracted with ethyl acetate (three times). The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated. The residue was subjected to silica gel column chromatography, and extracted with hexane-ethyl acetate (3: 2) eluate to give 2
473 mg (yield 24%) of-(benzylthio) acetic acid was obtained. 1 H-NMR (δ, CDCl 3 ): 3.11 (2H, s), 3.86 (2H, s), 7.23-7.37 (5
H (m, m) .IR (νcm -1 ,, neat): 3032,2920,1710,1496,1456,1424,130
0,1200,1132,930,768,702.
【００９７】[0097]
【発明の効果】本発明は、前記一般式（Ｉ）で表される
スルフェニル酢酸誘導体を工業的に入手容易な化合物か
ら高収率で製造することができる。INDUSTRIAL APPLICABILITY According to the present invention, the sulfenylacetic acid derivative represented by the general formula (I) can be produced from a compound which is industrially easily available in high yield.
───────────────────────────────────────────────────── 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 Ｂ０１Ｊ 31/14 Ｘ 31/22 Ｘ Ｃ０７Ｃ 319/20 7419−4Ｈ 323/60 7419−4Ｈ Ｃ０７Ｄ 307/38 307/42 333/34 // Ｃ０７Ｂ 61/00 ３００ ─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. 6 Identification code Internal reference number FI Technical display location B01J 31/14 X 31/22 X C07C 319/20 7419-4H 323/60 7419-4H C07D 307 / 38 307/42 333/34 // C07B 61/00 300
Claims (1)
させることを特徴とする一般式 【化３】 で表されるスルフェニル酢酸誘導体の製造法（式中Ｒ1
は、置換若しくは無置換の芳香族炭化水素又は置換若し
くは無置換の芳香族複素環基、Ｒ2 は、水素原子、アシ
ル基、アルキル基又はアルコキシカルボニル基であり、
Ｒ3 は、水酸基、アルコキシ基又はアミノ基であ
る。）。1. A compound of the general formula An alcohol derivative represented by the general formula A general formula characterized by reacting a mercaptan derivative represented by In the preparation of sulfenyl acid derivative represented (in the formula R 1
Is a substituted or unsubstituted aromatic hydrocarbon or a substituted or unsubstituted aromatic heterocyclic group, R 2 is a hydrogen atom, an acyl group, an alkyl group or an alkoxycarbonyl group,
R 3 is a hydroxyl group, an alkoxy group or an amino group. ).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP02580795A JP3233806B2 (en) | 1995-01-23 | 1995-01-23 | Method for producing sulfenylacetic acid derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP02580795A JP3233806B2 (en) | 1995-01-23 | 1995-01-23 | Method for producing sulfenylacetic acid derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH08198843A true JPH08198843A (en) | 1996-08-06 |
| JP3233806B2 JP3233806B2 (en) | 2001-12-04 |
Family
ID=12176146
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP02580795A Expired - Fee Related JP3233806B2 (en) | 1995-01-23 | 1995-01-23 | Method for producing sulfenylacetic acid derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3233806B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1437345A1 (en) * | 2003-01-13 | 2004-07-14 | Organisation de Synthese Mondiale Orsymonde | Novel method for preparing methyl 2-diphenylmethylsulfinylacetate |
-
1995
- 1995-01-23 JP JP02580795A patent/JP3233806B2/en not_active Expired - Fee Related
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1437345A1 (en) * | 2003-01-13 | 2004-07-14 | Organisation de Synthese Mondiale Orsymonde | Novel method for preparing methyl 2-diphenylmethylsulfinylacetate |
| WO2004063149A1 (en) * | 2003-01-13 | 2004-07-29 | Organisation De Synthese Mondiale Orsymonde | Method for preparing methyl 2-diphenylmethylsulfinylacetate |
| EA010381B1 (en) * | 2003-01-13 | 2008-08-29 | Сефалон Франс | Method for preparing methyl 2-diphenylmethylsulfinylacetate |
Also Published As
| Publication number | Publication date |
|---|---|
| JP3233806B2 (en) | 2001-12-04 |
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