JPS596867B2 - Calbostyril Yudou Tainoseizohou - Google Patents
Calbostyril Yudou TainoseizohouInfo
- Publication number
- JPS596867B2 JPS596867B2 JP6445475A JP6445475A JPS596867B2 JP S596867 B2 JPS596867 B2 JP S596867B2 JP 6445475 A JP6445475 A JP 6445475A JP 6445475 A JP6445475 A JP 6445475A JP S596867 B2 JPS596867 B2 JP S596867B2
- Authority
- JP
- Japan
- Prior art keywords
- formula
- general formula
- reaction
- yudou
- tainoseizohou
- 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
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 125000005606 carbostyryl group Chemical group 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 2
- 150000001875 compounds Chemical class 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 10
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 6
- JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000007800 oxidant agent Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 235000011054 acetic acid Nutrition 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- ZCDOYSPFYFSLEW-UHFFFAOYSA-N chromate(2-) Chemical compound [O-][Cr]([O-])(=O)=O ZCDOYSPFYFSLEW-UHFFFAOYSA-N 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- HDHQZCHIXUUSMK-UHFFFAOYSA-N 4-hydroxy-2-quinolone Chemical compound C1=CC=C2C(O)=CC(=O)NC2=C1 HDHQZCHIXUUSMK-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 150000001243 acetic acids Chemical class 0.000 description 1
- 239000000808 adrenergic beta-agonist Substances 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- DVECBJCOGJRVPX-UHFFFAOYSA-N butyryl chloride Chemical compound CCCC(Cl)=O DVECBJCOGJRVPX-UHFFFAOYSA-N 0.000 description 1
- QGJOPFRUJISHPQ-NJFSPNSNSA-N carbon disulfide-14c Chemical compound S=[14C]=S QGJOPFRUJISHPQ-NJFSPNSNSA-N 0.000 description 1
- -1 chromate ester Chemical class 0.000 description 1
- KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Chemical class O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- SOCTUWSJJQCPFX-UHFFFAOYSA-N dichromate(2-) Chemical compound [O-][Cr](=O)(=O)O[Cr]([O-])(=O)=O SOCTUWSJJQCPFX-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229940015043 glyoxal Drugs 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical class C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 1
- ZXZKYYHTWHJHFT-UHFFFAOYSA-N quinoline-2,8-diol Chemical group C1=CC(=O)NC2=C1C=CC=C2O ZXZKYYHTWHJHFT-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229940082569 selenite Drugs 0.000 description 1
- MCAHWIHFGHIESP-UHFFFAOYSA-L selenite(2-) Chemical compound [O-][Se]([O-])=O MCAHWIHFGHIESP-UHFFFAOYSA-L 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Landscapes
- Quinoline Compounds (AREA)
Description
【発明の詳細な説明】
本発明は新規なるカルボスチリル誘導体の製造法に関す
る。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for producing carbostyryl derivatives.
本発明で得られるカルボスチリル誘導体は一般式〔式中
Ｒ＿１、Ｒ＿２及びＲ＿３は水素原子又は炭素数１〜４
個の低級アルキル基を示す。The carbostyril derivative obtained in the present invention has the general formula [wherein R_1, R_2 and R_3 are hydrogen atoms or have 1 to 4 carbon atoms]
represents lower alkyl groups.
〕で表わされる化合物であつて、β−アドレナリン作働
薬の中間体として有用なものである。] and is useful as an intermediate for β-adrenergic agonists.
本発明に係るカルボスチリル誘導体は一般式〔式中Ｒ１
、Ｒ２及びＲ３は夫々上記と同様の意味を表わす。The carbostyryl derivative according to the present invention has the general formula [wherein R1
, R2 and R3 each have the same meaning as above.
〕で表わされる化合物を酸化することにより製造される
。] is produced by oxidizing the compound represented by
上記に於いて、Ｒ１、Ｒ２及びＲ３で示される炭素数１
〜４個の低級アルキル基としては例えばメチル、エチル
、プロピル、イソプロピル、Ｓｅｃブチル、 Ｔｅｒｔ
−ブチル等が挙げられる。In the above, the number of carbon atoms represented by R1, R2 and R3 is 1
Examples of ~4 lower alkyl groups include methyl, ethyl, propyl, isopropyl, Secbutyl, Tert
-butyl and the like.
本発明の出発物質である一般式（１）で表わされる化合
物は新規化合物である。該化合物は例えば公知０一般式
〔式中Ｒ１及びＲ２は夫々上記と同様の意味を表わす。The compound represented by general formula (1), which is the starting material of the present invention, is a new compound. The compound may be expressed, for example, by the well-known general formula (wherein R1 and R2 each represent the same meaning as above).
〕で表わされる化合物と一般式 〔式中Ｒ３は上記と同様の意味を表わす。] Compounds and general formula [In the formula, R3 represents the same meaning as above.
またＸは・・ロゲン原子を示す。〕で表わされる酸ハラ
イドとをフリーデルクラフツ触媒の存在下に反応させる
ことにより得られる。Moreover, X represents a rogen atom. ] with an acid halide in the presence of a Friedel-Crafts catalyst.
この反応に使用されるフリーデルクラフツ触媒としては
特に限定されないが、一般に無水塩化アルミニウム、チ
タンクロライド等が有利に用いられる。また一般式（）
で表わされる化合物と一般式（）で表わされる酸・・ラ
ードとの使用割合は適宜選択すればよいが、一般に前者
に対し後者を等モル〜５倍モル（好ましくは等モル〜３
倍モル）用いるのがよい。上記反応は無溶媒で行なつて
もよく、またジクロロエタン、ジクロロメタン等のハロ
ゲン化アルキル、二硫化炭素、ニトロベンゼン等の溶媒
中で行なつてもよい。また反応温度、反応時間は適宜選
択すればよいが、通常室温〜１２０℃（好ましくは５０
〜８０′Ｃ）で１〜１５時間（好ましくは３〜１０時間
）反応させることにより有利に進行する。この反応によ
り本発明に使用される一般式（１）で表わされる化合物
を得ることができる。本発明に於いて一般式（１）で表
わされる化合物の酸化反応は、広く酸化反応条件下に行
なうことができるが、通常は酸化剤の存在下に行なわれ
る。The Friedel-Crafts catalyst used in this reaction is not particularly limited, but anhydrous aluminum chloride, titanium chloride, etc. are generally advantageously used. Also general formula ()
The ratio of the compound represented by the formula () and the acid represented by the general formula ()... lard may be selected as appropriate, but generally the latter is used in an equimolar to 5-fold molar ratio (preferably an equimolar-3 molar ratio) to the former.
It is better to use 2 times the mole. The above reaction may be carried out without a solvent, or in a solvent such as an alkyl halide such as dichloroethane or dichloromethane, carbon disulfide, or nitrobenzene. The reaction temperature and reaction time may be selected as appropriate, but are usually room temperature to 120°C (preferably 50°C
The reaction proceeds advantageously by carrying out the reaction at a temperature of 1 to 15 hours (preferably 3 to 10 hours) at a temperature of 1 to 80'C. Through this reaction, the compound represented by the general formula (1) used in the present invention can be obtained. In the present invention, the oxidation reaction of the compound represented by general formula (1) can be carried out under a wide range of oxidation reaction conditions, but is usually carried out in the presence of an oxidizing agent.
この際使用される酸化剤としては、特に限定されないが
、一般に二酸化セレン、亜セレン酸並びに重クロム酸塩
、クロム酸塩、クロム酸塩化物、クロム酸エステル等の
クロム酸類が用いられる。本反応は一般に溶媒中で行な
われ、この際使用される溶媒としては、例えばジオキサ
ン、テトラヒドロフラン、ジエチルエーテル等のエーテ
ル類、酢酸、酢酸エチル等の酢酸類、水等が挙げられる
。反応温度は酸化剤の種類等により適宜選択すればよい
が、一般に室温乃至溶媒の還流温度附近（好ましくは６
０℃乃至溶媒の還流温度附近）で有利に進行する。本反
応により一般式（）で表わされる化合物の５位置換基−
ＣＯ−ＣＨ２−Ｒ３（Ｒ３は前記に同じ）のメチレン基
のみが酸化された本発明の目的化合物が得られる。The oxidizing agent used in this case is not particularly limited, but generally selenium dioxide, selenite, and chromic acids such as dichromate, chromate, chromate chloride, and chromate ester are used. This reaction is generally carried out in a solvent, and examples of the solvent used include ethers such as dioxane, tetrahydrofuran and diethyl ether, acetic acids such as acetic acid and ethyl acetate, and water. The reaction temperature may be appropriately selected depending on the type of oxidizing agent, etc., but is generally around room temperature or the reflux temperature of the solvent (preferably 6
The reaction proceeds advantageously at temperatures ranging from 0°C to around the reflux temperature of the solvent. In this reaction, the 5-position substituent of the compound represented by the general formula () -
The target compound of the present invention is obtained in which only the methylene group of CO-CH2-R3 (R3 is the same as above) is oxidized.
本発明の目的化合物は抽出、濃縮、洗浄、再結晶等の通
常の分離手段により精製することができる。本発明の原
料を得るための適当な方法を下記参考例に示し、引き続
き実施例を示す。The target compound of the present invention can be purified by conventional separation means such as extraction, concentration, washing, and recrystallization. A suitable method for obtaining the raw material of the present invention is shown in the following Reference Examples, followed by Examples.
参考例 １
８−ヒドロキシカルボスチリル１０ｙに二硫化炭素２０
ｍ１及び塩化ｎ−プチリル１８７を加えて氷冷攪拌下、
塩化アルミニウム２５ｙを少量ずつ加え十分混合する。Reference example 1 10y of 8-hydroxycarbostyryl and 20y of carbon disulfide
m1 and n-butyryl chloride 187 were added and stirred under ice cooling.
Add aluminum chloride 25y little by little and mix thoroughly.
次に浴温８０℃で１０時間加熱した後傾斜して二硫化炭
素層を除き、砕氷を加えて残留物を結晶化させる。析出
した結晶を沢取し、水洗、乾燥後メタノールより再結晶
して融点２２５洗Ｃ（分解点）の５−ｎ−ブチリル一８
ヒドロキシカルボスチリル１２．７７を得る。実施例
１
ジオキサン１００ｍ１に二酸化セレン１１．１ｆ７及び
水３ｍ１を加えて加熱し、該二酸化セレンを溶解し、５
−アセチル−８−ヒドロキシカルボスチリル２０．３ｙ
を加えて６時間加熱還流する。Next, after heating at a bath temperature of 80° C. for 10 hours, the carbon disulfide layer is removed by tilting, and crushed ice is added to crystallize the residue. A lot of precipitated crystals were collected, washed with water, dried, and then recrystallized from methanol to obtain 5-n-butyryl-8 with a melting point of 225C (decomposition point).
12.77 hydroxycarbostyril is obtained. Example
1 Add 11.1f7 of selenium dioxide and 3ml of water to 100ml of dioxane and heat to dissolve the selenium dioxide,
-acetyl-8-hydroxycarbostyryl 20.3y
and heated under reflux for 6 hours.
ジオキサン層を濃縮乾固し、残渣を沢取、水洗後エタノ
］＊−ルーエチルエーテルより再結晶して融点２９５〜
２９７℃の無色針状晶の（８−ヒドロキシカルボスチリ
ル−５−イル）グリオキサール１５．１７を得る。適当
な出発物質を用い上記実施例に準じて得られる本発明の
各化合物を下記第１表に示す。The dioxane layer was concentrated to dryness, the residue was collected, washed with water, and then recrystallized from ethyl ether, melting point 295~
15.17 of (8-hydroxycarbostyryl-5-yl)glyoxal is obtained as colorless needle-like crystals at 297°C. Compounds of the present invention obtained according to the above examples using appropriate starting materials are shown in Table 1 below.
Claims (1)
１〜４個の低級アルキル基を示す。 〕▲数式、化学式、表等があります▼ 〔式中Ｒ＿１、Ｒ＿２及びＲ＿３は夫々上記と同様の意
味を表わす。 〕で表わされるカルボスチリル誘導体の製造法。[Claims] 1 General formula ▲ Numerical formula, chemical formula, table, etc. ▼ [In the formula, R_1, R_2 and R_3 represent a hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms. ]▲There are mathematical formulas, chemical formulas, tables, etc.▼ [In the formula, R_1, R_2 and R_3 each represent the same meaning as above. ] A method for producing a carbostyryl derivative represented by
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6445475A JPS596867B2 (en) | 1975-05-28 | 1975-05-28 | Calbostyril Yudou Tainoseizohou |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6445475A JPS596867B2 (en) | 1975-05-28 | 1975-05-28 | Calbostyril Yudou Tainoseizohou |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS51141879A JPS51141879A (en) | 1976-12-07 |
| JPS596867B2 true JPS596867B2 (en) | 1984-02-15 |
Family
ID=13258696
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP6445475A Expired JPS596867B2 (en) | 1975-05-28 | 1975-05-28 | Calbostyril Yudou Tainoseizohou |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS596867B2 (en) |
-
1975
- 1975-05-28 JP JP6445475A patent/JPS596867B2/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| JPS51141879A (en) | 1976-12-07 |
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