JPS5822031B2 - β-Ketosulfoxides and their production method - Google Patents
β-Ketosulfoxides and their production methodInfo
- Publication number
- JPS5822031B2 JPS5822031B2 JP6062576A JP6062576A JPS5822031B2 JP S5822031 B2 JPS5822031 B2 JP S5822031B2 JP 6062576 A JP6062576 A JP 6062576A JP 6062576 A JP6062576 A JP 6062576A JP S5822031 B2 JPS5822031 B2 JP S5822031B2
- Authority
- JP
- Japan
- Prior art keywords
- double line
- multiplet
- allyloxyphenyl
- chloro
- chloroform
- 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.)
- Expired
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 150000003462 sulfoxides Chemical class 0.000 claims description 6
- 150000002148 esters Chemical class 0.000 claims description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 24
- 150000001875 compounds Chemical class 0.000 description 11
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 238000005481 NMR spectroscopy Methods 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 238000000921 elemental analysis Methods 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 206010030113 Oedema Diseases 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 235000010418 carrageenan Nutrition 0.000 description 3
- 229920001525 carrageenan Polymers 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- OTKFCIVOVKCFHR-UHFFFAOYSA-N (Methylsulfinyl)(methylthio)methane Chemical compound CSCS(C)=O OTKFCIVOVKCFHR-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 2
- 239000005977 Ethylene Substances 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 239000000679 carrageenan Substances 0.000 description 2
- 229940113118 carrageenan Drugs 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000010446 mirabilite Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- RSIJVJUOQBWMIM-UHFFFAOYSA-L sodium sulfate decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]S([O-])(=O)=O RSIJVJUOQBWMIM-UHFFFAOYSA-L 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 2
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- VOEFELLSAAJCHJ-UHFFFAOYSA-N 1-(3-chlorophenyl)-2-(methylamino)propan-1-one Chemical compound CNC(C)C(=O)C1=CC=CC(Cl)=C1 VOEFELLSAAJCHJ-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 230000003501 anti-edematous effect Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000000548 hind-foot Anatomy 0.000 description 1
- DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
【発明の詳細な説明】
本発明は一般式
（式中Ｒ１及びＲ２はアルキル基またはアリール基であ
る。DETAILED DESCRIPTION OF THE INVENTION The present invention is based on the general formula (wherein R1 and R2 are an alkyl group or an aryl group).
）で示されるβ−ケトスルホキシド類及びその製造法に
関するものである。) and its production method.
Ｒ１及びＲ２のアルキル基としてはメチル、エチル、プ
ロピル、ブチル基のようなアルキル基である。The alkyl groups for R1 and R2 include alkyl groups such as methyl, ethyl, propyl, and butyl groups.
具体的な化合物としては１−オキソ−１−（３−／；’
ロロー４−アリルオキシフェニル）−２−メチルスルフ
ィニル−２−メチルチオエタン、１−オキソ−１−（３
−り四〇−４−アリルオキシフェニル）−２−エチルス
ルフィニル−２−エチルチオエタン、１−オキソ−１−
（３−クロロ−４−アリルオキシフェニル）−２−プロ
ピルスルフィニル−２−プロピルチオエタン、１−オキ
ソ−１−（３−クロロ−４−アリルオキシフェニル）
−２−７−チルスルフィニル−２−ブチルチオエタン等
である。A specific compound is 1-oxo-1-(3-/;'
Rolow (4-allyloxyphenyl)-2-methylsulfinyl-2-methylthioethane, 1-oxo-1-(3
-40-4-allyloxyphenyl)-2-ethylsulfinyl-2-ethylthioethane, 1-oxo-1-
(3-chloro-4-allyloxyphenyl)-2-propylsulfinyl-2-propylthioethane, 1-oxo-1-(3-chloro-4-allyloxyphenyl)
-2-7-tylsulfinyl-2-butylthioethane and the like.
本発明で得られる化合物類はすべて文献未知物質であり
、ラットを用いてのカラゲニン浮腫法で消炎作用が認め
られ医薬品として有用なものである。All of the compounds obtained in the present invention are unknown substances in the literature, and their anti-inflammatory effect was observed in the carrageenan edema method using rats, and they are useful as pharmaceuticals.
また本発明で得られる化合物はこれより適邑な化学的手
段（下記参考側参照）を施すことにより消炎剤として賞
用されている式■で示される３−クロｃｌ −４−アリ
ルオキシフェニル酢酸に収率よく誘導できることから重
要な医薬品の中間体である。Furthermore, the compound obtained by the present invention can be obtained by applying appropriate chemical means (see reference side below) to obtain a compound of the formula (3), 3-chlorocl-4-allyloxyphenylacetic acid, which is used as an anti-inflammatory agent. It is an important pharmaceutical intermediate because it can be derived in good yield.
（式中Ｒ３はアルキル基である。(In the formula, R3 is an alkyl group.
）で示されるニス・チルと一般式
％式％（）
Ｃ式中Ｒ１及びＲ２はアルキル基またはアリール基であ
る。) and the general formula %Formula %()C In the formula, R1 and R2 are an alkyl group or an aryl group.
）で示されるα位にスルフィド結合を有するスルホキシ
ドとを塩基の存在下に反応させることにより前記一般式
（Ｉ）で表わされるところの新規化合物であるβ−ケト
スルホキシド類を製造する方法も抱括するものである。) is reacted with a sulfoxide having a sulfide bond at the α-position in the presence of a base to produce β-ketosulfoxides, which are novel compounds represented by the general formula (I). It is something to do.
この反応の実施に幽って反応溶媒としてはテトラヒドロ
フラン、ジエチルエーテル、ジオキサン、■、２−ジメ
トキシエタン、ベンゼン、トルエンの如き反応に関与し
ない非プロトン性有機溶媒を用いることが出来る。In carrying out this reaction, aprotic organic solvents that do not participate in the reaction, such as tetrahydrofuran, diethyl ether, dioxane, 2-dimethoxyethane, benzene, and toluene, can be used as the reaction solvent.
また本反応では塩基の存在が必須で、用いる塩基として
は例えば水素化ナトリウム、水素化カリウム、ブチルリ
チウム、メチルリチウム、リチウムジイソプロピルアミ
ド等の如き強塩基が好ましい。Further, the presence of a base is essential in this reaction, and the base used is preferably a strong base such as sodium hydride, potassium hydride, butyllithium, methyllithium, lithium diisopropylamide, and the like.
エステル（ｎ）とα位にスルフィド結合を有するスルホ
キシド（２）の使用量は等モル量で十分であり、また塩
基の使用量は（２）に対して２当量が好ましいが所望で
あれば過剰に加えても良い。Equimolar amounts of the ester (n) and the sulfoxide (2) having a sulfide bond at the α-position are sufficient, and the amount of the base used is preferably 2 equivalents relative to (2), but an excess can be added if desired. May be added to.
反応は室温下で円滑に進行し、所望であれば加温しても
よい。The reaction proceeds smoothly at room temperature, and may be heated if desired.
反応時間は１〜４０時間で十分である。A reaction time of 1 to 40 hours is sufficient.
本発明で得られた化合物類は文献未知であり、赤外線吸
収スペクトル、核磁気共鳴スペクトルおよび元素分析に
よりその構造を確認した。The compounds obtained in the present invention are unknown in the literature, and their structures were confirmed by infrared absorption spectroscopy, nuclear magnetic resonance spectroscopy, and elemental analysis.
次に実施例及び参考例にて本反応を具体的に説明するが
これに限定されるものではない。Next, this reaction will be specifically explained in Examples and Reference Examples, but is not limited thereto.
ン実流側 １
メチルメチルチオメチルスルホキシド１．０’１をテト
ラヒドロフラン１０ｍ１にとかし、水冷下水素化ナトリ
ウム（５０係含有）９００１ｎ９を加え３０分攪拌する
。Actual stream side 1 Dissolve 1.0'1 of methyl methylthiomethyl sulfoxide in 10 ml of tetrahydrofuran, add 9001 n9 of sodium hydride (containing 50%) under water cooling, and stir for 30 minutes.
室温下、３−クロロ−４−アリ；ルオキシ安息香酸メチ
ル２．０ｇを加え、更に１９時間攪拌する。At room temperature, 2.0 g of methyl 3-chloro-4-aryloxybenzoate was added, and the mixture was further stirred for 19 hours.
クロロホルム４０ ｍｌ、酢酸５ｍｌおよび水２ＴＬｌ
を加えたのち、芒硝と炭酸カリウムで乾燥する。40 ml of chloroform, 5 ml of acetic acid and 2 TL of water
After adding , it is dried with Glauber's salt and potassium carbonate.
溶媒を減圧濃縮後カラムクロマトグラフィー（シリカゲ
ル、クロロホルム）により分離：し、１−オキソ−１−
（３−クロロ−４−アリルオキシフェニル）−２−メチ
ルスルフィニル−２−メチルチオエタン１．９５１収率
７０係）を淡黄色油状物質として得た。After concentrating the solvent under reduced pressure, it was separated by column chromatography (silica gel, chloroform), and 1-oxo-1-
(3-chloro-4-allyloxyphenyl)-2-methylsulfinyl-2-methylthioethane (1.951 yield, 70%) was obtained as a pale yellow oil.
このものはＮＭＲから２種の立体異性体の３＝４混合物
であることが明らかとなった。NMR revealed that this product was a 3=4 mixture of two stereoisomers.
ＩＲ（ｎｅａｔ） ： Ｉ ６６０ＣｒｆＬ−１と１０
５０ｃｍ−’ＮＭＲ（ＣＤＣｌ２）：
成分Ａ：δ２．１２（３Ｈ，−重線）、２．８７（３Ｈ
５−重線）。IR (neat): I 660CrfL-1 and 10
50 cm-'NMR (CDCl2): Component A: δ2.12 (3H, - double line), 2.87 (3H
5-double line).
成分Ｂ：δ２．２２（３Ｈ，−重線）、２．６４（３Ｈ
９−重線）。Component B: δ2.22 (3H, - double line), 2.64 (3H
9- double line).
成分Ａ、Ｂ共通：δ４．６５（２Ｈ，二重線、Ｊ＝４．
５Ｈｚ） 、 ５．１８−６．３０ （３Ｈ。Common to components A and B: δ4.65 (2H, double line, J=4.
5Hz), 5.18-6.30 (3H.
多重線）、５．５５（ＩＨ，−重線）。multiplet), 5.55 (IH, - multiplet).
６．８５−８．０ （３Ｈ，多重線）。6.85-8.0 (3H, multiplet).
元素分析（Ｃ１３Ｈ１５０３ＣＩＳ２）：計算値（イ）
：Ｃ、４８，９６；Ｈ，４，７４：Ｓ 。Elemental analysis (C13H1503CIS2): Calculated value (a)
:C, 48,96; H, 4,74:S.
２０．１１゜ 実験値（イ）：Ｃ、４８，８７：Ｈ，４，５８：Ｓ 。20.11° Experimental values (a): C, 48,87:H, 4,58:S.
１９．９３゜
実施例 ２
メチルメチルチオメチルスルホキシド２．２１．９をテ
トラヒドロフラン２０ｒＩＬｌに溶かし、−１５°Ｃで
ｎ−ブチルリチウムのヘキサン溶液（１，４ｍｍｏ ｌ
／ｒｒｔｌ ） １３ ｍｌを加えて同温で３０分攪拌
する。19.93゜Example 2 Methylmethylthiomethylsulfoxide 2.21.9 was dissolved in 20rILl of tetrahydrofuran, and a hexane solution of n-butyllithium (1.4mmol
/rrtl) 13 ml was added and stirred at the same temperature for 30 minutes.
３−クロロ−４−アリルオキシ安息香酸エチル２．１１
．９を加えて一１５℃で２時間、室温で１０時間攪拌す
る。Ethyl 3-chloro-4-allyloxybenzoate 2.11
．． 9 was added and stirred at -15°C for 2 hours and at room temperature for 10 hours.
以下実施例１と同様の処理をして、１−オキソ−１−（
３−クロロ−４−アリルオキシフェニル）−２−メチル
スルフィニル−２−メチルチオエタン２．１６．９（収
率７７係）を淡黄色油状物質として得た。Thereafter, the same treatment as in Example 1 was carried out, and 1-oxo-1-(
2.16.9 (yield: 77%) of 3-chloro-4-allyloxyphenyl)-2-methylsulfinyl-2-methylthioethane was obtained as a pale yellow oil.
参考例 １
１−オキソ−１−（３−り四ロー４−アリルオキシフェ
ニル）−２−メチルスルフィニル−２−メチルチオエタ
ン１．ＯＪをメタノール５０７７１１に溶解し、水冷下
、水素化ホウ素ナトリウム１２０１ｎ９を加え、室温で
３時間攪拌したのちアセトンＩＴｔｌにて過剰の水素化
ホウ素ナトリウムを分解し、減圧濃縮する。Reference Example 1 1-oxo-1-(3-ri-4-allyloxyphenyl)-2-methylsulfinyl-2-methylthioethane 1. OJ is dissolved in methanol 507711, sodium borohydride 1201n9 is added under water cooling, and after stirring at room temperature for 3 hours, excess sodium borohydride is decomposed with acetone ITtl and concentrated under reduced pressure.
残留物にクロロホルム３０Ｉ７１１を加え抽出し、水１
０ｍ１で洗浄する。The residue was extracted with chloroform 30I711, and water 1
Wash with 0ml.
クロロホルム層は芒硝にて乾燥後、減圧留去し、四塩化
炭素より結晶化し、１−ヒドロキシ−１−（３−クロロ
−４−アリルオキシフェニル）−２−メチルスルフィニ
ル−２−メチルチオエタンを３種の立体異性体混合物と
して無色結晶で５２０７Ｑ（収率５１係）得た。The chloroform layer was dried over Glauber's salt, evaporated under reduced pressure, and crystallized from carbon tetrachloride to give 1-hydroxy-1-(3-chloro-4-allyloxyphenyl)-2-methylsulfinyl-2-methylthioethane. 5207Q (yield: 51%) was obtained as colorless crystals as a mixture of stereoisomers.
この混合物は、メタノールより分別再結晶を行ない融点
１６２−１６３℃の無色針状晶（異性体ａ）および融点
１０３〜１０５℃の無色針林晶（異性体ｂ）を得た。This mixture was fractionally recrystallized from methanol to obtain colorless needle crystals (isomer a) with a melting point of 162-163°C and colorless needle crystals (isomer b) with a melting point of 103-105°C.
又四塩化炭素結晶化母液は、減圧濃縮後カラムクロマト
グラフィー（シリカゲル、クロロホルム）で分離し、無
色油状物（（異性体ｃ）２５０■および４種の異性体混
合物７０ｍｆｌを得た。The carbon tetrachloride crystallization mother liquor was concentrated under reduced pressure and separated by column chromatography (silica gel, chloroform) to obtain 250 μl of a colorless oil ((isomer c) and 70 mfl of a mixture of four isomers.
全収率８４０■（８３’ｌ）。異性体（ａ）：
ＩＲ（ＫＢｒ） ： ３２００ｃｍ−１とｌ０４０ｃｆ
ＩＬ−１ＮＭＲ（ｄ ｓ −ＤＭＳ Ｏ） ：δ１．９
３（３Ｈ，−重線）２．７７（３Ｈ，−重線）、３．７
８
（Ｉｎ２幅広い一重線）、４．６３ 。Total yield: 840 sq. (83'l). Isomer (a): IR (KBr): 3200cm-1 and 1040cf
IL-1NMR (ds-DMSO): δ1.9
3 (3H, - double line) 2.77 (3H, - double line), 3.7
8 (In2 wide singlet), 4.63.
（２Ｈ５二重線、Ｊ＝４．５Ｈｚ） 。(2H5 doublet, J=4.5Hz).
５．２０−６．３５ （４Ｈ、多重線）。5.20-6.35 (4H, multiplet).
６．８−７．７（３Ｈ，多重線）。6.8-7.7 (3H, multiplet).
異性体（ｂ）：
ＩＲ（ＫＢｒ） ： ３２００ｃｍ−’とｌ０３５ｃｆ
ＩＬ−” 。Isomer (b): IR (KBr): 3200cm-' and l035cf
IL-”.
ＮＭＲ（ｄ ｓ −ＤＭＳ Ｏ） ：δ２．０５（３Ｈ
，−重線）。NMR (ds-DMSO): δ2.05 (3H
, - heavy line).
２４３０（３Ｈ，−重線）、３．５７ （ＩＨ５二重線、 Ｊ＝５Ｈｚ） 。2430 (3H, - double line), 3.57 (IH5 double line, J=5Hz).
４．７０（２Ｈ，二重線、Ｊ＝４．５
Ｈｚ）、 ５．００ （Ｉ Ｈを二重線、Ｊ＝５Ｈｚ）
、 ５．２５−６．４０ （３Ｈ、多重線） 、 ６．
８−７．８ （３Ｈ、多重線）。4.70 (2H, double line, J=4.5 Hz), 5.00 (IH double line, J=5Hz)
, 5.25-6.40 (3H, multiplet), 6.
8-7.8 (3H, multiplet).
異性体（Ｃ）：
ＩＲ（ｎｅｓｔ）： ３３００ｃｙｒＬ−’と１０１０
ｃｆｒＬ−”ＮＭＲ（ＣＤＣ１３）：δ１．９６（３Ｈ
，−重線）。Isomer (C): IR (nest): 3300 cyrL-' and 1010
cfrL-”NMR (CDC13): δ1.96 (3H
, - heavy line).
２．７０ （３Ｈ、−重線）、３．７６ （ＩＨ５二重線、Ｊ＝８Ｈｚ）。2.70 (3H, - double line), 3.76 (IH5 doublet, J=8Hz).
４．５２（２Ｈ，二重線ｖ Ｊ ＝４．５ Ｈｚ ）
１４．８２（ＩＨ，二重線、Ｊ＝８Ｈ２）。4.52 (2H, double line v J = 4.5 Hz)
14.82 (IH, double line, J=8H2).
５．１０−６．３０ （３Ｈ，多重線）。5.10-6.30 (3H, multiplet).
６．７−７．５ （３Ｈ、多重線）。6.7-7.5 (3H, multiplet).
３立体異性体の結晶性混合物の元素分析 （Ｃ１３Ｈ１７０３Ｓ２Ｃｌ）： 計算値（ト）：Ｃ，４８，６６；Ｈ，５，３４；Ｓ。Elemental analysis of a crystalline mixture of three stereoisomers (C13H1703S2Cl): Calculated value (g): C, 48,66; H, 5,34; S.
１９．９８゜ 実験値（イ）：Ｃ、４８，７４：Ｈ，５，３３；Ｓ 。19.98° Experimental values (a): C, 48,74: H, 5,33; S.
２０．１５
参考例 ２
１−ヒドロキシ−１−（３−クロロ−４−アリルオキシ
フェニル）−２−メチルスルフィニル−２−メチルチオ
エタン〔参考例２で得られた異性体（ｃ）〕１００ｍ？
、ピリジン２５ｍ１．無水酢酸２．５７７１１の混合物
を室温で１５時間攪拌したのち、過剰のピリジン及び無
水酢酸を減圧留去する。20.15 Reference Example 2 1-Hydroxy-1-(3-chloro-4-allyloxyphenyl)-2-methylsulfinyl-2-methylthioethane [isomer (c) obtained in Reference Example 2] 100m?
, 25 ml of pyridine. After stirring a mixture of 2.57711 acetic anhydride at room temperature for 15 hours, excess pyridine and acetic anhydride were distilled off under reduced pressure.
残渣はクロロホルム２０ＴＬｌに溶解し、水５ｍｌで洗
浄し芒硝乾燥後溶媒留去。The residue was dissolved in 20 TL of chloroform, washed with 5 ml of water, dried over sodium sulfate, and the solvent was distilled off.
更にカラムクロマトグラフィー（シリカゲル、クロロホ
ルム）により分離精製し、１−アセトキシ−１−（３−
クロロ−４−アリルオキシフェニル）−２−メチルスル
フィニル−２−メチルチオエタンを油状物として１００
■（収率９０係）得た。It was further separated and purified by column chromatography (silica gel, chloroform) to obtain 1-acetoxy-1-(3-
100% of chloro-4-allyloxyphenyl)-2-methylsulfinyl-2-methylthioethane as an oil.
(yield: 90%) was obtained.
ＩＲ（ｎｅａｔ）： １７４０ｃｍ ’ＮＭＲ（ＣＤ
ＣＩ３）：δ２．０８（３Ｈ，−重線）。IR(neat): 1740cm'NMR(CD
CI3): δ2.08 (3H, - double line).
２．２０（３Ｈ，−重線）、２．６９（３Ｈ，−重線）
、 ４．２４（ＩＨ，二重線、 Ｊ＝８Ｈｚ ） 。2.20 (3H, - double line), 2.69 (3H, - double line)
, 4.24 (IH, double line, J=8Hz).
４．６６（２Ｈ，二重線、Ｊ＝４．５
Ｈｚ）、 ６．０５ （１Ｈを二重線、Ｊ＝８Ｈｚ）
、 ５．２５−６．３０ （３Ｈ、多重線） 、 ６．
７−７．７ （３Ｈ，多重線）。4.66 (2H, double line, J=4.5 Hz), 6.05 (1H double line, J=8Hz)
, 5.25-6.30 (3H, multiplet), 6.
7-7.7 (3H, multiplet).
元素分析（Ｃ１５Ｈ１９０４Ｓ２Ｃ■）：計算値（イ）
：Ｃ，４９，６４；Ｈ，５，２７；Ｓ。Elemental analysis (C15H1904S2C■): Calculated value (a)
:C,49,64;H,5,27;S.
１７．６７゜ 実験値（イ）：Ｃ、４９，５８；Ｈ，５，３１；Ｓ 。17.67° Experimental values (a): C, 49,58; H, 5,31; S.
１７．７７゜
参考例 ３
１−アセトキシ−１−（３−クロロ−４−アリルオキシ
フェニル）−２−メチルスルフィニル−２−メチルチオ
エタン４５０７ｎ９をメタノール２５ＴＬｌに溶解し、
トリエチルアミン０．４ ｍｌを加えた後、８時間加熱
環流する。17.77゜Reference Example 3 Dissolve 4507n9 of 1-acetoxy-1-(3-chloro-4-allyloxyphenyl)-2-methylsulfinyl-2-methylthioethane in 25TLl of methanol,
After adding 0.4 ml of triethylamine, the mixture was heated under reflux for 8 hours.
溶媒を減圧留去後カラムクロマトグラフィー（シリカゲ
ル、クロロホルム）により分離精製し、１−メチルスル
フィニル−１−メチルチオ−２−（３−クロロ−４−ア
リルオキシフェニル）エチレン３４０〜（収率ｓｏ％）
を得た。After distilling off the solvent under reduced pressure, it was separated and purified by column chromatography (silica gel, chloroform) to obtain 1-methylsulfinyl-1-methylthio-2-(3-chloro-4-allyloxyphenyl)ethylene 340 ~ (yield so%)
I got it.
ＩＲ（ｎｅａｔ） ： Ｉ Ｏ６０ｃｍ、−’ＮＭＲ
（ＣＣＩ４）：δ２．３０（３Ｈ，−重線）。IR (neat): IO60cm, -'NMR
(CCI4): δ2.30 (3H, - double line).
２．６２（３Ｈ，−重線）、４．６２
（２Ｈ２二重線ｔ Ｊ ＝４．５ Ｈｚ ） ｔ５．２
０−６．３５ （３Ｈ、多重線）。2.62 (3H, - double line), 4.62 (2H2 double line t J = 4.5 Hz) t5.2
0-6.35 (3H, multiplet).
７．４２（Ｉｎ、−重線）、６．８９− ８．０６（３Ｈ，多重線）。7.42 (In, - double line), 6.89- 8.06 (3H, multiplet).
元素分析（Ｃ１３Ｈ０５０２Ｓ２Ｃ■）：計算値（イ）
：Ｃ、５１，５６；Ｈ，４，９９；Ｓ 。Elemental analysis (C13H0502S2C■): Calculated value (a)
:C, 51,56; H, 4,99; S.
２１．１７゜ 実験値（イ）：Ｃ，５１，６２；Ｈ，４，９３；Ｓ。21.17° Experimental values (a): C, 51,62; H, 4,93; S.
２１．２５゜
参考例 ４
】−メチルスルフィニル−１−メチルチオ−２−（３−
クロロ−４−アリルオキシフェニル）エチレン２．６ｇ
を１，２−ジメトキシエタン２０ｍ１に溶解した後、濃
塩酸８ＴＬｌを少量づつ加え室温で２５時間攪拌する。21.25゜Reference Example 4 ]-Methylsulfinyl-1-methylthio-2-(3-
2.6 g of chloro-4-allyloxyphenyl)ethylene
After dissolving in 20ml of 1,2-dimethoxyethane, 8TLl of concentrated hydrochloric acid was added little by little and stirred at room temperature for 25 hours.
クロロホルム１５０ＴＩＬｌと水３０ＴＬｌを加えたの
ち、水層をさらにクロロホルム５０ＴＬｌで抽出する。After adding 150 TL of chloroform and 30 TL of water, the aqueous layer is further extracted with 50 TL of chloroform.
有機層をあわせ無水硫酸マグネシウムで乾燥後クロロホ
ルムを留去、残留物にエーテル１００１ｒＬｌを加え、
重炭酸ナトリウム飽和水溶液で抽出する（６０ｍｌｌで
２回）。The organic layers were combined, dried over anhydrous magnesium sulfate, chloroform was distilled off, and ether 1001rLl was added to the residue.
Extract with saturated aqueous sodium bicarbonate solution (2 x 60 ml).
水層を塩酸。で酸性にしたのちクロロホルムで抽出する
（１００ｍｌで３回）。Add hydrochloric acid to the aqueous layer. After acidifying with water, extract with chloroform (3 times with 100 ml).
抽出液を無水硫酸マグネシウムで乾燥後溶媒を留去し、
シクロヘキサンから結晶化、再結晶して融点９］−９２
°Ｃの無色針状晶として３−クロロ−４−アリルオキシ
フェニル酢酸１．６８ｇ（収率８６．８係）を得た。After drying the extract over anhydrous magnesium sulfate, the solvent was distilled off.
Crystallized from cyclohexane, recrystallized with melting point 9]-92
1.68 g (yield: 86.8%) of 3-chloro-4-allyloxyphenylacetic acid was obtained as colorless needle-like crystals.
ＩＲ（ＫＢｒ） ： １６９０ｃｒＩＬ−’ＮＭＲ（Ｃ
ＤＣＩ３） ：δ３．５２（２Ｈ，−重線）。IR(KBr): 1690crIL-'NMR(C
DCI3): δ3.52 (2H, - double line).
４．５８（２Ｈ，二重線、Ｊ ＝＝４．５Ｈｚ ） ｔ
５．１８−６．３２ （３Ｈ、多重線）。4.58 (2H, double line, J ==4.5Hz) t
5.18-6.32 (3H, multiplet).
６．７２−７．５２ （３Ｈ、多重線）。6.72-7.52 (3H, multiplet).
１１．５６（ＩＨ，−重線）。11.56 (IH, - double line).
元素分析（Ｃ１１Ｈ１１０３Ｃ■）：
計算値□□□：Ｃ，６０，９８；Ｈ，５，１１゜実験値
（イ）：Ｃ、６１，０５；Ｈ，５，０６゜カラゲニン浮
腫法による本発明化合物の消炎作用く実験法〉
実施例１で得た本発明化合物を０．３ ％カルボキシメ
チルセルロース・ナトリウム（ＣＭＣ−Ｎａ）に懸濁し
、ＳＤ系雌雄性ラット１群５匹、体重１１０〜１４０ｇ
）に経口投与した。Elemental analysis (C11H1103C■): Calculated value □□□: C, 60,98; H, 5,11° Experimental value (a): C, 61,05; H, 5,06° Compound of the present invention by carrageenin edema method Experimental method for anti-inflammatory effect> The compound of the present invention obtained in Example 1 was suspended in 0.3% sodium carboxymethylcellulose (CMC-Na), and a group of 5 SD male and female rats weighed 110 to 140 g.
) was administered orally.
投与１時間後に１係カラゲニン溶液０．１ ｍｌを各ラ
ットの右後肢足耶に皮下投与し、その後１時間毎に定容
積を測定し、次式：
（但し、ＥＣはコントロール群の浮腫強度の平均値を、
ＥＤは被験薬投与群の浮腫強度を示す）により抑制率（
係）を算出し′差。One hour after administration, 0.1 ml of the 1st carrageenan solution was subcutaneously administered to the right hind foot of each rat, and a constant volume was then measured every hour. The average value,
ED indicates the edema intensity of the study drug administration group), and the inhibition rate (
) and calculate the difference.
なお、コントロール群は被験薬の代りに０．３係ＣＭＣ
−Ｎａのみを経口投与した。The control group received 0.3 CMC instead of the test drug.
-Na alone was orally administered.
また対照薬としてフェニルブタシン（ＰＢ）を用いた。Furthermore, phenylbutacin (PB) was used as a control drug.
く結果〉
本発明化合物および対照薬の１２．５．２５．５０およ
び１００■／ｋｙの各投与量における抑制率（被験薬の
投与後３時間での値）を表１に示す。Results> Table 1 shows the inhibition rates (values 3 hours after administration of the test drug) of the compound of the present invention and the control drug at each dose of 12.5, 25.50 and 100 μ/ky.
表１
抑制率（イ）
投与量（１ｒｖｋｇ） １２．５ ２５ ５０
１００投与群
対照薬（ＰＢ） １１．７ １６，７ ３２．９
３７．５本発明化合物 ２２．９ ２１．０ ４２．
９ ４４．０（実施例１）
表１に示す如く、本発明化合物はＰＢに優る抗浮腫活性
を示した。Table 1 Inhibition rate (a) Dose (1rvkg) 12.5 25 50
100 administration group control drug (PB) 11.7 16,7 32.9
37.5 Compound of the present invention 22.9 21.0 42.
9 44.0 (Example 1) As shown in Table 1, the compound of the present invention exhibited anti-edema activity superior to PB.
Claims (1)
ことを特徴とする一般式 （式中Ｒ１およびＲ２はアルキル基である。 ）で示されるβ−ケトスルホキシド類の製造法。[Claims] 1 In the general formula c, R1 and R2 are an alkyl group. ) β-Ketosulfoxides represented by 2. Reacting an ester represented by the general formula (in which R3 is an alkyl group) and a sulfoxide represented by the general formula % (in the formula, R1 and R2 are an alkyl group) in the presence of a strong base. A method for producing β-ketosulfoxides represented by the general formula (wherein R1 and R2 are alkyl groups), characterized by:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6062576A JPS5822031B2 (en) | 1976-05-27 | 1976-05-27 | β-Ketosulfoxides and their production method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6062576A JPS5822031B2 (en) | 1976-05-27 | 1976-05-27 | β-Ketosulfoxides and their production method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS52144645A JPS52144645A (en) | 1977-12-02 |
| JPS5822031B2 true JPS5822031B2 (en) | 1983-05-06 |
Family
ID=13147656
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP6062576A Expired JPS5822031B2 (en) | 1976-05-27 | 1976-05-27 | β-Ketosulfoxides and their production method |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5822031B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10984998B2 (en) | 2017-10-26 | 2021-04-20 | Shimadzu Corporation | Mass spectrometer |
-
1976
- 1976-05-27 JP JP6062576A patent/JPS5822031B2/en not_active Expired
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10984998B2 (en) | 2017-10-26 | 2021-04-20 | Shimadzu Corporation | Mass spectrometer |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS52144645A (en) | 1977-12-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US3853952A (en) | 2-ethynylcyclopropane compounds and process for the preparation thereof | |
| PT89409A (en) | PROCESS FOR THE PREPARATION OF NEW 3,5-DIHYDROXYCARBOXYL ACIDS AND THEIR DERIVATIVES, OF PHARMACEUTICAL COMPOSITIONS CONTAINING THESE COMPOUNDS, AS WELL AS INTERMEDIATE PRODUCTS FOR THE SYNTHESIS OF THE NEW COMPOUNDS | |
| CA2107150C (en) | Chromenic derivatives having a triene lateral chain, process for the preparation thereof and pharmaceutical compositions containing them | |
| JPS5822031B2 (en) | β-Ketosulfoxides and their production method | |
| US4906757A (en) | Process for the preparation of dextrorotatory 3-(3-pyridyl)-1H,3H-pyrrolo [1,2-c]-7-thiazolecarboxylic acid | |
| CN102153455B (en) | A method for synthesizing multiple substituted 3-phenyl four-membered cycloalkenes | |
| JPS588391B2 (en) | α-Hydroxyaldehyde mercaptal S-oxides and their production method | |
| JPH0358335B2 (en) | ||
| US3712928A (en) | Phenylcyclohexane derivatives and methods for their manufacture | |
| CN110804069A (en) | Preparation method of thio-phosphine (phosphate) ester substituted allene compound | |
| US4169953A (en) | Tricyclo[4.3.1.12,5 ]undecane-1-carboxylic acid and derivatives thereof and a process for producing the same | |
| JPH02290830A (en) | Production of glutaric acid derivative | |
| CN113583012B (en) | Synthesis method of pyrano [4,3-b ] pyridine-2, 7-dione compound | |
| JPS5822032B2 (en) | β-oxysulfoxide derivative and method for producing the same | |
| JPS63264448A (en) | Novel beta-ketonitrile | |
| JPS599536B2 (en) | Kanjiyouka Gobutsuno Seizouhou | |
| US5041620A (en) | Method for producing optically active 2-cyclopenten-4-one-1-ol esters, 2-cyclopenteno-4-one-1-ol ester and complexes thereof with optically active 1,6-diphenyl-2,4-hexadiyne-1,6-diol | |
| JPS5811437B2 (en) | 1-Sulfinyl-1-thio-2-(3-chloro-4-allyloxyphenyl)ethylene | |
| JPH10251217A (en) | New benzenesulfonylamine derivative, its production and pharmaceutical composition containing the same | |
| Landesberg et al. | Addition of N-bromosuccinimide to 3-sulfolene | |
| JPH0129793B2 (en) | ||
| JP2765575B2 (en) | Process for producing substituted cyclopentenone and substituted cyclohexenone derivatives | |
| US4176196A (en) | Hypoglycemic arylcyclohexane acetic acids | |
| JPH03127780A (en) | Anilinopyrimidine derivative | |
| JPH0812658A (en) | Production of sydnones |