JPS5899480A - Novel chroman derivative - Google Patents
Novel chroman derivativeInfo
- Publication number
- JPS5899480A JPS5899480A JP19609781A JP19609781A JPS5899480A JP S5899480 A JPS5899480 A JP S5899480A JP 19609781 A JP19609781 A JP 19609781A JP 19609781 A JP19609781 A JP 19609781A JP S5899480 A JPS5899480 A JP S5899480A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- formula
- dione
- heating
- spiro
- 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.)
- Granted
Links
- VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical class C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 title claims description 3
- 150000001875 compounds Chemical class 0.000 abstract description 23
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 abstract description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 abstract description 7
- 210000000695 crystalline len Anatomy 0.000 abstract description 7
- 239000002904 solvent Substances 0.000 abstract description 7
- 238000010438 heat treatment Methods 0.000 abstract description 6
- 238000006243 chemical reaction Methods 0.000 abstract description 5
- 230000000694 effects Effects 0.000 abstract description 5
- 230000002401 inhibitory effect Effects 0.000 abstract description 5
- 230000008961 swelling Effects 0.000 abstract description 5
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 abstract description 4
- 102000016912 Aldehyde Reductase Human genes 0.000 abstract description 4
- 108010053754 Aldehyde reductase Proteins 0.000 abstract description 4
- 125000000217 alkyl group Chemical group 0.000 abstract description 4
- NDKBVBUGCNGSJJ-UHFFFAOYSA-M benzyltrimethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)CC1=CC=CC=C1 NDKBVBUGCNGSJJ-UHFFFAOYSA-M 0.000 abstract description 3
- 238000000034 method Methods 0.000 abstract description 3
- 229920000137 polyphosphoric acid Polymers 0.000 abstract description 3
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 abstract description 2
- 239000001099 ammonium carbonate Substances 0.000 abstract description 2
- 235000012501 ammonium carbonate Nutrition 0.000 abstract description 2
- 239000012024 dehydrating agents Substances 0.000 abstract description 2
- 238000003402 intramolecular cyclocondensation reaction Methods 0.000 abstract description 2
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 abstract description 2
- 239000003795 chemical substances by application Substances 0.000 abstract 2
- NYISILLQMHWGTP-UHFFFAOYSA-N 3'-sulfanylspiro[2,3-dihydrochromene-4,5'-imidazolidine]-2',4'-dione Chemical compound SN1C(NC2(C1=O)CCOC1=CC=CC=C12)=O NYISILLQMHWGTP-UHFFFAOYSA-N 0.000 abstract 1
- 230000003301 hydrolyzing effect Effects 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 239000013078 crystal Substances 0.000 description 8
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- SOOARYARZPXNAL-UHFFFAOYSA-N 2-(Methylthio)phenol Chemical compound CSC1=CC=CC=C1O SOOARYARZPXNAL-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 125000004414 alkyl thio group Chemical group 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 235000017168 chlorine Nutrition 0.000 description 2
- 125000001309 chloro group Chemical class Cl* 0.000 description 2
- 238000012136 culture method Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000002826 placenta Anatomy 0.000 description 2
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- NMCXSNYBUXYMLO-UHFFFAOYSA-N 3-(4-methylsulfanylphenoxy)propanoic acid Chemical compound CSC1=CC=C(OCCC(O)=O)C=C1 NMCXSNYBUXYMLO-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 101100256637 Drosophila melanogaster senju gene Proteins 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 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
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000000460 chlorine Chemical group 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- KMPWYEUPVWOPIM-KODHJQJWSA-N cinchonidine Chemical compound C1=CC=C2C([C@H]([C@H]3[N@]4CC[C@H]([C@H](C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-KODHJQJWSA-N 0.000 description 1
- KMPWYEUPVWOPIM-UHFFFAOYSA-N cinchonidine Natural products C1=CC=C2C(C(C3N4CCC(C(C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-UHFFFAOYSA-N 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 150000002344 gold compounds Chemical class 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- WQGWDDDVZFFDIG-UHFFFAOYSA-N pyrogallol Chemical compound OC1=CC=CC(O)=C1O WQGWDDDVZFFDIG-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Landscapes
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】 本発明は新規なタロマン誘導体に関する。[Detailed description of the invention] The present invention relates to novel taloman derivatives.
次式［Ｙ］で示されるスピロ−［タロマン−４゜４′−
イミダゾリジン］−２’、ｆｆ−ジオン０６位にフッ素
、塩素、臭素もしくはメトキシ基が置換し、または６．
７もしくは６．８位に２個の塩素が置換した化合物はす
でに発表されている（西独特許出願公告第１．ｌ１５．
９１５号、特公昭５５−８４１８２号、特開昭５３−１
４４５７５号）。Spiro-[taloman-4゜4'-
imidazolidine]-2', ff-dione substituted with fluorine, chlorine, bromine or methoxy group at the 06 position, or 6.
Compounds in which two chlorines are substituted at the 7 or 6.8 position have already been announced (West German Patent Application Publication No. 1.l15.
No. 915, JP 55-84182, JP 53-1
No. 44575).
しかしながら、化合物［Ｙ］がアルキルメルカプト基で
置換されたもの（↓未だ知られていない。However, compounds in which the compound [Y] is substituted with an alkylmercapto group (↓not yet known).
本発明者らは置換基として低級アルキルメルカプト基を
有筆る化合物を合成し、それが有用な薬理活性を示すこ
とを発見して、本発明を確立するに至った。The present inventors synthesized a notable compound having a lower alkylmercapto group as a substituent, discovered that it exhibited useful pharmacological activity, and established the present invention.
本発明は、式
で示される６−低級アルキルメルカプドースビロー［タ
ロマン−４，４′−イミダゾリジン］ ２／ 、 ５／
−ジオンよりなる新規クロマン誘導体である。The present invention provides 6-lower alkyl mercapdose birow [taloman-4,4'-imidazolidine] 2/, 5/
- It is a new chroman derivative consisting of dione.
本発明の化合物は、たとえば、下記のようにして製造さ
れうる。The compound of the present invention can be produced, for example, as follows.
先ス、ｐ−低級アルキルメルカプトフェノールをアクリ
ロニトリルと反応させて３−（ｐ−低級アルキルメルカ
プトフェノキシ）プロピオニトリル〔ｎ′〕を得る。こ
の反応は、好ましくはトリトンＢのような促進剤の存在
下に溶媒中で行われる。First, p-lower alkylmercaptophenol is reacted with acrylonitrile to obtain 3-(p-lower alkylmercaptophenoxy)propionitrile [n']. This reaction is preferably carried out in a solvent in the presence of a promoter such as Triton B.
溶媒の好ましい例は含水メタノールである。A preferred example of the solvent is aqueous methanol.
化合物［ＩＶ］を加水分解すれば相当するカルボン酸す
なわち３−（ｐ−低級アルキルメルカプトフェノキシ〕
−プロピオン酸〔■〕が得られる。When compound [IV] is hydrolyzed, the corresponding carboxylic acid, namely 3-(p-lower alkylmercaptophenoxy)
-Propionic acid [■] is obtained.
加水分解は、たとえば濃塩酸と加熱することによって行
われる。Hydrolysis is carried out, for example, by heating with concentrated hydrochloric acid.
次に化合物［ＩＮを分子内閉環反応に付じて４−低級ア
ルキルメルカプト−４−タロマノン［ＩＩ］を得る。こ
の反応は化合物［■］をポリリン酸のような脱水剤と加
熱することによって行われる。Next, the compound [IN is subjected to an intramolecular ring closure reaction to obtain 4-lower alkylmercapto-4-talomanone [II]. This reaction is carried out by heating the compound [■] with a dehydrating agent such as polyphosphoric acid.
続いて、化合物［Ｕ］に、たとえばシアンカリウムと炭
酸アンモニクムを作用させると本発明の６−低級アルキ
ルメルカプドースピロー［タロマン−４，４′−イミダ
ゾリジン］−１，５’−ジオン［Ｉｌが得られる。Subsequently, when the compound [U] is reacted with, for example, potassium cyanide and ammonium carbonate, the 6-lower alkylmercapdose pyro[taloman-4,4'-imidazolidine]-1,5'-dione [Il is obtained.
反応は、たとえば、エタノール、ジオキサン、エチレン
グリコール、ジメチルホルムアミドのような水溶性含酸
素有機溶媒を用い、耐圧容器中で溶媒の沸点以上に加熱
して行うこともできるが。The reaction can also be carried out, for example, by using a water-soluble oxygen-containing organic solvent such as ethanol, dioxane, ethylene glycol, or dimethylformamide, and heating it to a temperature above the boiling point of the solvent in a pressure-resistant container.
沸点未満の温間で行うこともできる。It can also be carried out at temperatures below the boiling point.
上記の反応は次式に示される。The above reaction is shown in the following equation.
〔■〕〔。〕
Ｃ式中、Ｒは低級アルキル基を表わす）化合物［Ｉｌは
構造式中に不岑炭素を有するので、通常ラセミ型として
得られ、るが、これは公知の方法により、たとえばプル
シン、シンコニジンのような光学活性の塩基を低級アル
コール中で作用させて偏左右異性体塩を生成させ、これ
を分別結晶したのち酸で分解することにより、光学分割
することができる。[■] [. [In the formula C, R represents a lower alkyl group] Compound [Il has an essential carbon in the structural formula, so it is usually obtained as a racemic type, but this can be obtained by a known method, such as purusin, cinchonidine, etc. Optical resolution can be achieved by reacting such an optically active base in a lower alcohol to produce a left-right isomer salt, which is fractionally crystallized and then decomposed with an acid.
化合物（Ｉｌは著るしいＡＲ阻害作用を有する。Compound (Il) has a significant AR inhibitory effect.
代表的な６−２メチルメルカプドースビロー〔クロ（１
）人胎盤ＡＲの阻害作用
上記化合物（Ａ）のアルドース還元酵素活性の阻害作用
をＳ、 Ｈａｙｍｅｎ ｅｂ ａｌ、 、 Ｊｏｕｒｎ
ａｌ ｏｆ Ｂｉ。Typical 6-2 methyl mercapdose billow [chloro(1
) Inhibitory effect on human placenta AR The inhibitory effect of the above compound (A) on aldose reductase activity was determined by S. Haymen et al., Journal.
al of Bi.
ｌｏｇｉｃａｌ ＣｈｅｍｉｓｔｒｙｔＶｏｌ、２４０
，８７７（１９６５）およびＪｉｎ Ｈ，Ｋｉｎｏｓｈ
ｉ’ｔａ ｅｔ ａｌ、、Ｍｅｔａｂｏｌｉｓｍ。Logical Chemistry Vol, 240
, 877 (1965) and Jin H, Kinosh.
i'ta et al., Metabolism.
ＶＯｌ、２８１Ｎｒ、４．５ｕＥ）１）１１，４６２（
１９７９）等に記載された方法に準じて試験した。試験
に使用した酵素は人胎盤からとった部分的に精製された
アルドース還元酵素である。比較のために既知化合物６
−フルオル−スピロ−［タロマン−４，４′−イミダゾ
リジノ］ −２／ 、 ５／−ジオン（Ｂ）を用い、化
合物の濃度を種々変更して各濃度における酵素活性を測
定し、活性−阻害率をチとして表記する。VOl, 281Nr, 4.5uE) 1) 11,462(
The test was conducted according to the method described in (1979) et al. The enzyme used in the test was partially purified aldose reductase from human placenta. Known compound 6 for comparison
-Fluoro-spiro-[taloman-4,4'-imidazolidino]-2/, 5/-dione (B) was used, the concentration of the compound was varied, the enzyme activity at each concentration was measured, and the activity-inhibition rate was determined. is expressed as chi.
（幻 ラット水晶体培養法での水晶体膨潤抑制作用（３
０ｍＭキジローズ添加培養液中で４８時間培養・）
前記Ａ、Ｂ両化金化合物ット水晶体培養法による水晶体
膨潤抑制効果をＨ，Ｏｂａｚａｗａ ｅｔ ａｌ、。(Illusion: Suppression of crystalline lens swelling in rat lens culture method (3)
Cultured for 48 hours in a culture medium supplemented with 0mM Pheasant Rose. The effect of suppressing lens swelling by the A and B amphoteric gold compound lens culture method was reported by H. Obazawa et al.
工ｎｖｅｓｔ、ｏｐｈｔｈａ１ｍｏｘ Ｖｏｌ １３．
ＩＪｒ、３，２Ｑ４（１９７４）に記載された方法によ
って試験した。Engineering best, ophthalmox Vol 13.
IJr, 3, 2Q4 (1974).
各化合物について得られた結果は水晶体の膨潤抑制率と
して次表に示す。The results obtained for each compound are shown in the following table as the swelling inhibition rate of the crystalline lens.
米水分（１ｗｖ）／乾燥重量（Ｉ Ｑｉｙ）以上のよう
に、本発明の化合物は化合物（Ｂ）にくらべ、五Ｒ明書
作用および水晶体膨潤抑制作用がすぐれている。As can be seen from the rice water content (1wv)/dry weight (I Qiy), the compound of the present invention is superior to compound (B) in its five-R clarification effect and lens swelling-inhibiting effect.
次に実施例の形で本発明化合物の製造例を示す。Next, production examples of the compounds of the present invention will be shown in the form of examples.
実施例
ｐ−メチルメルカプトフェノール（１ｏＦ）とアクリロ
ニトリル（５７Ｆ）との混合物に攪拌しながら少量のト
リトンＢ（ベンジルトリメチルアンモニクムヒドロキシ
ド）の４０１メタノール溶液１．５−を加え、１８時間
加熱還流、攪拌を続−けたのち、反応混合物を室温に放
置した。クロロホルム２００ｍｅを加えて不溶物を沖去
し、Ｆ液を５％Ｎａ０）Ｔ水溶液１０ｍｅずつで８回、
次いで希塩酸１０ｍｅずつで２回、最後に水２Ｏｍｅず
つで３回水洗し、無水Ｎａ２ＳＯ４で乾燥後、溶媒を留
去して粗結晶１１ｙを得た。これを９５％エタノールか
ら再結晶して、無色針状晶、ｍｐ８４−８６℃の３−（
ｐ−メチルメルカプト７エ／キシ）プロピオニトリル１
０．７ ？ （収率７８％〕を得た。Example p-To a mixture of methylmercaptophenol (1oF) and acrylonitrile (57F) was added a small amount of 401 methanol solution 1.5- of Triton B (benzyltrimethylammonicum hydroxide) with stirring, and heated under reflux for 18 hours. After continued stirring, the reaction mixture was left at room temperature. Add 200me of chloroform to remove insoluble matter, and add 10me of 5% Na0)T aqueous solution to solution F 8 times.
Next, it was washed twice with 10 me each of diluted hydrochloric acid and finally three times with 20 me each of water, dried over anhydrous Na2SO4, and the solvent was distilled off to obtain crude crystals 11y. This was recrystallized from 95% ethanol to give colorless needle crystals, mp 84-86°C, 3-(
p-Methylmercapto 7eth/xy)propionitrile 1
0.7? (Yield 78%) was obtained.
工Ｒ（ＫＢｒ）ｃｍ ：２２５０．１６００Ｐ Ｍ
Ｒ（ＣＤ Ｃ／ Ｂ ）δ：２．４８（３Ｈ，ＥＩ）
、２．７９（２Ｈ，ｔ、Ｊ−７Ｈｚ）、４１６（２Ｈ，
ｔ、Ｊ−７Ｈ２）、６．８２（２Ｈ，ｄｄ、；−８Ｈ２
，１，５Ｈ２）。Engineering R (KBr) cm: 2250.1600P M
R (CD C / B ) δ: 2.48 (3H, EI)
, 2.79 (2H, t, J-7Hz), 416 (2H,
t, J-7H2), 6.82 (2H, dd,;-8H2
, 1, 5H2).
７．２８（２Ｈ，ａｄ、Ｊ−８Ｈ２，１，５Ｈ２）３−
（ｐ−メチルメルカプトフェノキシ）プロピオニトリル
（５２〕を濃塩酸（約１５ｍｅ）に溶解し、１８時間加
熱還流した。反応混合物を氷（約１００ｙ）上に注ぎ、
析出した結晶を沖取し。7.28 (2H, ad, J-8H2,1,5H2)3-
(p-Methylmercaptophenoxy)propionitrile (52) was dissolved in concentrated hydrochloric acid (approximately 15 me) and heated under reflux for 18 hours. The reaction mixture was poured onto ice (approximately 100 y).
Offshore the precipitated crystals.
冷水で洗浄後、１０チＮａＯＨ水溶液（約１５０ｍ／）
に溶解した。不溶物を戸去し、涙液をＨＣＩ 酸性と
し、析出する結晶をｐ取し０、水洗後、クロロホルムに
加温しながら溶解した。グロロホルム層を乾燥後、溶媒
を留去して無色結晶の３−（ｐ−メチルメルカプトフェ
ノキシ〕−プロピオン酸８．８２（収率６１％）を得た
。After washing with cold water, 10 t NaOH aqueous solution (approx. 150 m/)
dissolved in. Insoluble materials were removed, the lachrymal fluid was acidified with HCI, and the precipitated crystals were removed to zero, washed with water, and then dissolved in chloroform with heating. After drying the gloloform layer, the solvent was distilled off to obtain 8.82 g of 3-(p-methylmercaptophenoxy)-propionic acid (yield: 61%) as colorless crystals.
工Ｒ（ＫＢｒ）ｃｍ ：３１ＱＱ−２５ＱＱ（ｂｒ
。Engineering R (KBr) cm: 31QQ-25QQ (br
.
ａｄ）、１６８０ＰＭＲ（ＣＤＣｌ２：ＣＤＢＯＤ−１
０：１）δ：２．７０（２Ｈ，ｔ、、Ｔ−７Ｈｚ）、４
２７（２Ｈ１ｔｌＪ−７Ｈ２）１４９６（ＩＨｌｂ）、
６．８８（２Ｈ，ｄ４．Ｊ−８Ｈ２，１，５Ｈ２）１７
．８″ｏ（２’Ｈ、ｄａ 、 Ｊ−８Ｈ２、１，５−Ｈ
ｚ ）８−（’９−メチルメルカプトフェノキシ）プロ
ピオン酸（８，２９）にポリリン酸（３２Ｆ）を加え、
攪拌しながら水溶に、１５分間加温した。反応混合物を
氷（約３０（１）上に注ぎ、酢酸エチル７０ｍｅずつで
８回抽出した。酢酸エチル層を無水Ｍｙ８０４で乾燥し
、乾燥剤を戸去し、ｐ液から溶媒を留去′した。残った
液体を減圧蒸留して６−メチルメルカブトー４−クロマ
ノン２．ｏｒ（ｆｆｌ率６９チ）を得た。ｂｐＨ５−１
１８℃（０，４２Ｔｏｒｒ）−１゜
工Ｒ（ｌｉｑｕｉｄ ｆｉｌｍ）ａｍ 、２９８
０Ｉ２９１０．２８７０．１６８０．１５９５ｐＭＲ（
ｃＤｃｌｓ）ｌｊ： ２．４５（８Ｈ，＋３）、２．７
９（２Ｈ１ｔ、Ｊ−６Ｈ２）１４５１（２Ｈ，ｔ、、Ｔ
−６Ｈ２）、ｆｉ、８７（ｌＨ，ｄ４．、Ｔ＝１３Ｉ（
Ｚ、ｌＨ２）。ad), 1680PMR (CDCl2:CDBOD-1
0:1) δ: 2.70 (2H, t, , T-7Hz), 4
27 (2H1tlJ-7H2) 1496 (IHlb),
6.88 (2H, d4.J-8H2, 1, 5H2) 17
．． 8″o(2’H, da, J-8H2, 1,5-H
z) Add polyphosphoric acid (32F) to 8-('9-methylmercaptophenoxy)propionic acid (8,29),
The aqueous solution was heated for 15 minutes while stirring. The reaction mixture was poured onto ice (approx. 30(1)) and extracted 8 times with 70ml of ethyl acetate. The ethyl acetate layer was dried with anhydrous My804, the desiccant was removed, and the solvent was distilled off from the p solution. The remaining liquid was distilled under reduced pressure to obtain 6-methylmercabuto-4-chromanone 2.or (ffl ratio 69). bpH 5-1
18℃(0.42Torr)-1℃R(liquid film)am, 298
0I2910.2870.1680.1595pMR(
cDcls) lj: 2.45 (8H, +3), 2.7
9 (2H1t, J-6H2) 1451 (2H,t,,T
-6H2), fi, 87(lH, d4., T=13I(
Z, lH2).
＝７．３９（ｌＨ，ｍ）、７．７５（ｌＨ，（１，Ｊ−
２Ｉ（Ｚ）ＫｃＮ（ｘ、５’ｐ）と（ＮＩ（４）２ＣＯ
３（Ｍｌ）の混合物に５０％エタノール（２０ｍｌ’）
を加え、攪拌しなから浴温６４−６６℃で６７時間加温
した。反応混合物を氷水で冷却後、水（約１５ｍｅ）を
加え、（ＩＮ−ＨＣ／で酸性とし、析出する固体を戸数
し、充分水洗後、２Ｎ−ＮａＯＨ（５０ｍ（りに溶解し
、酢酸エチル１５ｍｅずつで３回抽出した。=7.39(lH,m), 7.75(lH,(1,J-
2I(Z)KcN(x, 5'p) and (NI(4)2CO
50% ethanol (20 ml') to a mixture of 3 (Ml)
was added, and the mixture was heated at a bath temperature of 64-66°C for 67 hours without stirring. After cooling the reaction mixture with ice water, water (approximately 15 ml) was added, acidified with (IN-HC/), the precipitated solid was collected, washed thoroughly with water, and then dissolved in 2N-NaOH (50 ml) and 15 ml of ethyl acetate. Extracted three times.
アルカリ性水性層を６Ｎ−ＨＣ／で酸性とし、析出する
結晶を戸数し、水でよく洗浄し、減圧乾燥して粗結晶２
．１］を得た。これを９５チエタノールから再結晶して
、無色プリズム晶、ｍｐ１８８カ
ー１８９℃の（１／−メチルメｉつ°ドースピロー〔タ
ロマン−４，４′−イミダゾリジンＥ−２’＋５’−ジ
オン１．４９ （収率３７．５ ％ ）を得た。The alkaline aqueous layer was made acidic with 6N-HC/, and the precipitated crystals were collected, washed thoroughly with water, and dried under reduced pressure to obtain crude crystals 2.
．． 1] was obtained. This was recrystallized from 95% ethanol to give colorless prismatic crystals. (yield 37.5%).
ＩＲ（ＫＢｒ）ａｍ ：ａａ５ｏ、ａ２ｏｏ、ａｏ
５０．１７８０．１７２０
ＰＭＲ（ＣＤＣ／３：ＣＤ３０Ｄ−５：３）δ：２．０
３−２．４６（２Ｈ，ｍ）、２．３９（３ＨＩ Ｅｌ）
、２．９３−４．８Ｍ４Ｈ，ｍ）、６．７３−７．４７
（３Ｈ，ｍ）元素分析値 組成式： Ｃ＋２Ｈ＋２Ｎ２
０ａＳ計算値 Ｃ；５４５５．Ｎｉ４５５．Ｎｉ１Ｏ，
６１測定値 Ｃ；５４６４．Ｈ；４４９．Ｎｉ１０．５
７出 願 人 千寿製薬株式会社IR(KBr)am :aa5o, a2oo, ao
50.1780.1720 PMR (CDC/3:CD30D-5:3) δ:2.0
3-2.46 (2H, m), 2.39 (3HI El)
, 2.93-4.8M4H, m), 6.73-7.47
(3H, m) Elemental analysis value Composition formula: C+2H+2N2
0aS calculation value C; 5455. Ni455. Ni1O,
61 measurement value C; 5464. H;449. Ni10.5
7 Applicant: Senju Pharmaceutical Co., Ltd.
Claims (1)
ロマン−４，４′−イミダゾリジン〕−２７゜５′−ジ
オンよりなる新規クロマン誘導体[Scope of Claims] A novel chroman derivative consisting of 6-lower alkylmercapdose [taloman-4,4'-imidazolidine]-27°5'-dione not represented by the formula
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP19609781A JPS5899480A (en) | 1981-12-04 | 1981-12-04 | Novel chroman derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP19609781A JPS5899480A (en) | 1981-12-04 | 1981-12-04 | Novel chroman derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5899480A true JPS5899480A (en) | 1983-06-13 |
| JPS634831B2 JPS634831B2 (en) | 1988-02-01 |
Family
ID=16352161
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP19609781A Granted JPS5899480A (en) | 1981-12-04 | 1981-12-04 | Novel chroman derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5899480A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0317230U (en) * | 1989-06-30 | 1991-02-20 |
-
1981
- 1981-12-04 JP JP19609781A patent/JPS5899480A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS634831B2 (en) | 1988-02-01 |
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