JPH046707B2 - - Google Patents
Info
- Publication number
- JPH046707B2 JPH046707B2 JP62290757A JP29075787A JPH046707B2 JP H046707 B2 JPH046707 B2 JP H046707B2 JP 62290757 A JP62290757 A JP 62290757A JP 29075787 A JP29075787 A JP 29075787A JP H046707 B2 JPH046707 B2 JP H046707B2
- Authority
- JP
- Japan
- Prior art keywords
- formula
- compound
- general formula
- compound represented
- bromo
- 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 - Lifetime
Links
- 150000001875 compounds Chemical class 0.000 claims description 23
- -1 1,4-dihydro-4-oxoquinoline compound Chemical class 0.000 claims description 19
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 8
- 238000010438 heat treatment Methods 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 125000001153 fluoro group Chemical group F* 0.000 claims description 5
- GXHFUVWIGNLZSC-UHFFFAOYSA-N meldrum's acid Chemical compound CC1(C)OC(=O)CC(=O)O1 GXHFUVWIGNLZSC-UHFFFAOYSA-N 0.000 claims description 5
- LTMHNWPUDSTBKD-UHFFFAOYSA-N diethyl 2-(ethoxymethylidene)propanedioate Chemical compound CCOC=C(C(=O)OCC)C(=O)OCC LTMHNWPUDSTBKD-UHFFFAOYSA-N 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 230000000911 decarboxylating effect Effects 0.000 claims description 2
- 230000003301 hydrolyzing effect Effects 0.000 claims description 2
- RLAHWVDQYNDAGG-UHFFFAOYSA-N Methanetriol Chemical compound OC(O)O RLAHWVDQYNDAGG-UHFFFAOYSA-N 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 30
- 238000006243 chemical reaction Methods 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- 239000000243 solution Substances 0.000 description 20
- 239000013078 crystal Substances 0.000 description 18
- 239000007787 solid Substances 0.000 description 18
- 238000001914 filtration Methods 0.000 description 15
- MHCVCKDNQYMGEX-UHFFFAOYSA-N 1,1'-biphenyl;phenoxybenzene Chemical compound C1=CC=CC=C1C1=CC=CC=C1.C=1C=CC=CC=1OC1=CC=CC=C1 MHCVCKDNQYMGEX-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 239000000843 powder Substances 0.000 description 12
- 239000007810 chemical reaction solvent Substances 0.000 description 11
- 238000002844 melting Methods 0.000 description 11
- 230000008018 melting Effects 0.000 description 11
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 6
- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 4
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 4
- IRFSXVIRXMYULF-UHFFFAOYSA-N 1,2-dihydroquinoline Chemical compound C1=CC=C2C=CCNC2=C1 IRFSXVIRXMYULF-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-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
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 235000019484 Rapeseed oil Nutrition 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- ROBKVGDBQLURAF-UHFFFAOYSA-N 1,4-dihydroquinoline Chemical compound C1=CC=C2CC=CNC2=C1 ROBKVGDBQLURAF-UHFFFAOYSA-N 0.000 description 2
- BUTIDJREEDINSI-UHFFFAOYSA-N 2-bromo-4,5-difluoroaniline Chemical compound NC1=CC(F)=C(F)C=C1Br BUTIDJREEDINSI-UHFFFAOYSA-N 0.000 description 2
- ZPMKGKUWDFEBFB-UHFFFAOYSA-N 2-bromo-4-chloro-5-fluoroaniline Chemical compound NC1=CC(F)=C(Cl)C=C1Br ZPMKGKUWDFEBFB-UHFFFAOYSA-N 0.000 description 2
- QNKQNJJCNWUOHC-UHFFFAOYSA-N 2-bromo-5-chloro-4-fluoroaniline Chemical compound NC1=CC(Cl)=C(F)C=C1Br QNKQNJJCNWUOHC-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- BQHDXNZNSPVVKB-UHFFFAOYSA-N diethyl 2-methylidenepropanedioate Chemical compound CCOC(=O)C(=C)C(=O)OCC BQHDXNZNSPVVKB-UHFFFAOYSA-N 0.000 description 2
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- XJDDLMJULQGRLU-UHFFFAOYSA-N 1,3-dioxane-4,6-dione Chemical compound O=C1CC(=O)OCO1 XJDDLMJULQGRLU-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- MAMRRASCBCVQHO-UHFFFAOYSA-N 2-bromo-4,5-dichloroaniline Chemical compound NC1=CC(Cl)=C(Cl)C=C1Br MAMRRASCBCVQHO-UHFFFAOYSA-N 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- ZCILODAAHLISPY-UHFFFAOYSA-N biphenyl ether Natural products C1=C(CC=C)C(O)=CC(OC=2C(=CC(CC=C)=CC=2)O)=C1 ZCILODAAHLISPY-UHFFFAOYSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- PUSKHXMZPOMNTQ-UHFFFAOYSA-N ethyl 2,1,3-benzoselenadiazole-5-carboxylate Chemical compound CCOC(=O)C1=CC=C2N=[Se]=NC2=C1 PUSKHXMZPOMNTQ-UHFFFAOYSA-N 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- QEZIFBAXJMHDJP-UHFFFAOYSA-N n-chloro-4-fluoroaniline Chemical compound FC1=CC=C(NCl)C=C1 QEZIFBAXJMHDJP-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- PMZDQRJGMBOQBF-UHFFFAOYSA-N quinolin-4-ol Chemical compound C1=CC=C2C(O)=CC=NC2=C1 PMZDQRJGMBOQBF-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
Landscapes
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
- Quinoline Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
【発明の詳細な説明】
産業上の利用分野
本発明は、下記一般式［］：
（式中、Ｘ及びＹは同一又は異なつてフツ素原
子又は塩素原子を夫々表わす。）
で示される１，４−ジヒドロ−４−オキソキノリ
ン化合物（以下単に「本発明化合物［］とい
う）及びその製造法に関する。DETAILED DESCRIPTION OF THE INVENTION Industrial Field of Application The present invention relates to the following general formula []: (In the formula, X and Y are the same or different and represent a fluorine atom or a chlorine atom, respectively.) Regarding manufacturing methods.
従来の技術
本発明化合物［］は本発明者らにより初めて
合成されたものであり、公知文献未記載の化合物
である。Prior Art The compound of the present invention [ ] was synthesized for the first time by the present inventors, and is a compound that has not been described in any known literature.
発明が解決しようとする問題点
本発明化合物［］は、本発明者らの一部ほか
により開発中の新規な９−ハロゲノ−５−アルキ
ル−８−無置換乃至三置換ピペラジニル−ベンゾ
［ij］キノリジン−２−カルボン酸系抗菌剤の製
造中間体として有用である。Problems to be Solved by the Invention The compound of the present invention [] is a novel 9-halogeno-5-alkyl-8-unsubstituted to trisubstituted piperazinyl-benzo[ij] currently under development by some of the present inventors and others. It is useful as an intermediate in the production of quinolidine-2-carboxylic acid antibacterial agents.
問題点を解決するための手段
本発明化合物［］は、下記一般式［］：
（式中、Ｘ及びＹは前記と同意義である。）
で示されるアニリン化合物と、２，２−ジメチル
−１，３−ジオキサン−４，６−ジオン及びオル
トギ酸エチルとを反応させ、下記一般式［］：
（式中、Ｘ及びＹは前記と同意義である。）
で示される化合物に変換し（以下ａ工程という）、
この化合物［］をついで加熱閉環する（以下ｂ
工程という）ことにより製造することができる。Means for Solving the Problems The compound of the present invention [] has the following general formula []: (wherein, General formula []: (In the formula, X and Y have the same meanings as above.) (hereinafter referred to as step a),
This compound [ ] is then heated and ring-closed (hereinafter b
(referred to as a process).
ａ工程の反応は、無溶媒又は反応溶媒中、20〜
110℃、好ましくは50〜110℃で、15分〜10時間、
好ましくは30分〜５時間行う。反応溶媒として
は、メタノール、エタノール、プロピルアルコー
ル、ベンゼンもしくはトルエン又はこれらの二種
以上からなる混合液などが挙げられる。アニリン
化合物［］に対する使用量は、２，２−ジメチ
ル−１，３−ジオキサン−４，６−ジオン及びオ
ルトギ酸エチルともに、１〜６倍モル、好ましく
は１〜３倍モルとする。同じく反応溶媒は0.5〜
20倍重量、好ましくは１〜10倍重量とする。 The reaction in step a is carried out without a solvent or in a reaction solvent for 20 to
110℃, preferably 50-110℃, 15 minutes to 10 hours,
Preferably it is carried out for 30 minutes to 5 hours. Examples of the reaction solvent include methanol, ethanol, propyl alcohol, benzene, toluene, and a mixture of two or more thereof. The amount of both 2,2-dimethyl-1,3-dioxane-4,6-dione and ethyl orthoformate to be used is 1 to 6 times the mole, preferably 1 to 3 times the mole relative to the aniline compound []. Similarly, the reaction solvent is 0.5~
20 times the weight, preferably 1 to 10 times the weight.
ｂ工程の加熱閉環反応は、ａ工程で得られる化
合物［］を、伝熱媒体中、120〜300℃、好まし
くは170〜260℃で、２分〜５時間、好ましくは５
分〜２時間行う。伝熱媒体としては、ダウサーム
Ａ（ビフエニルとジフエニルエーテルとの混合物）
又はナタネ油などが挙げられ、その使用量は、化
合物［］に対して１〜50倍重量、好ましくは２
〜10倍重量とする。 In the heating ring-closing reaction in step b, the compound obtained in step a is heated in a heat transfer medium at 120 to 300°C, preferably 170 to 260°C, for 2 minutes to 5 hours, preferably 5 hours.
Do this for minutes to 2 hours. As a heat transfer medium, Dowtherm A (mixture of biphenyl and diphenyl ether)
or rapeseed oil, etc., and the amount used is 1 to 50 times the weight of the compound [], preferably 2 times the weight.
~10 times the weight.
また、本発明化合物［］は、前記一般式
［］で示されるアニリン化合物とエトキシメチ
レンマロン酸ジエチルとを反応させ、下記一般式
［］：
（式中、Ｘ及びＹは前記と同意義である。）
で示される化合物を生成し（以下ｃ工程という）、
この化合物［］を加熱閉環して下記一般式
［］：
（式中、Ｘ及びＹは前記と同意義である。）
で示される化合物に変換し（以下ｄ工程という）、
ついでこの化合物［］を加水分解し（以下ｅ工
程という）、最後に脱炭酸する（以下ｆ工程とい
う）ことによつても製造することができる。 The compound of the present invention [] can be obtained by reacting the aniline compound represented by the general formula [] with diethyl ethoxymethylenemalonate, and the compound [] is prepared by the following general formula []: (In the formula, X and Y have the same meanings as above.) Produce a compound represented by (hereinafter referred to as step c),
This compound [] is ring-closed by heating to form the following general formula []: (In the formula, X and Y have the same meanings as above.) (hereinafter referred to as step d),
It can also be produced by subsequently hydrolyzing this compound [] (hereinafter referred to as step e) and finally decarboxylating it (hereinafter referred to as step f).
ｃ工程の反応は、無溶媒又は反応溶媒中、20〜
190℃、好ましくは60〜150℃で、１〜10時間、好
ましくは２〜６時間行う。反応溶媒としては、メ
タノール、エタノール、プロピルアルコール、ベ
ンゼン、トルエン、酢酸エチル、Ｎ，Ｎ−ジメチ
ルホルムアミドもしくはジメチルスルホキシド又
はこれらの二種以上からなる混合液が挙げられ
る。エトキシメチレンマロン酸ジエチルは、アニ
リン化合物［］に対して１〜５倍モル、好まし
くは１〜２倍モル使用する。反応溶媒を用いる場
合、その反応溶媒の使用量は、アニリン化合物
［］に対して１〜50倍重量、好ましくは３〜20
倍重量とする。 The reaction in step c is carried out without a solvent or in a reaction solvent for 20~
It is carried out at 190°C, preferably 60-150°C, for 1-10 hours, preferably 2-6 hours. Examples of the reaction solvent include methanol, ethanol, propyl alcohol, benzene, toluene, ethyl acetate, N,N-dimethylformamide, dimethyl sulfoxide, or a mixture of two or more thereof. Diethyl ethoxymethylenemalonate is used in a molar amount of 1 to 5 times, preferably 1 to 2 times, based on the aniline compound []. When a reaction solvent is used, the amount of the reaction solvent used is 1 to 50 times the weight of the aniline compound [], preferably 3 to 20 times the weight of the aniline compound [].
Double the weight.
ｄ工程の加熱閉環反応は、ｃ工程で得られる化
合物［］を、伝熱媒体中、200〜300℃、好まし
くは250〜280℃で、10分〜10時間、好ましくは30
分〜３時間行う。伝熱媒体としては、ダウサーム
Ａ又はナタネ油などが挙げられ、その使用量は、
化合物［］に対して１〜50倍重量、好ましくは
２〜10倍重量とする。 In the heating ring-closing reaction in step d, the compound obtained in step c is heated in a heat transfer medium at 200 to 300°C, preferably 250 to 280°C, for 10 minutes to 10 hours, preferably 30
Do this for minutes to 3 hours. Examples of the heat transfer medium include Dowtherm A or rapeseed oil, and the amount used is:
The amount is 1 to 50 times, preferably 2 to 10 times the weight of the compound [].
ｅ工程の加水分解反応は、酸又はアルカリの過
剰量を用い、反応溶媒中、０〜120℃、好ましく
は使用反応溶媒の還流温度で、15分〜10時間、好
ましくは30分〜３時間行う。酸としては希塩酸ま
たは希硫酸などが、アルカリとしては水酸化ナト
リウム又は水酸化カリウムの水溶液がそれぞれ挙
げられる。反応溶媒としては、メタノール、エタ
ノール、プロピルアルコール、ジオキサン又は酢
酸などが挙げられる。なお、反応溶媒の使用量
は、前工程で得られる化合物［］に対して１〜
50倍重量、好ましくは５〜10倍重量とする。 The hydrolysis reaction in step e is carried out using an excess amount of acid or alkali in a reaction solvent at 0 to 120°C, preferably at the reflux temperature of the reaction solvent used, for 15 minutes to 10 hours, preferably 30 minutes to 3 hours. . Examples of the acid include dilute hydrochloric acid or dilute sulfuric acid, and examples of the alkali include an aqueous solution of sodium hydroxide or potassium hydroxide. Examples of the reaction solvent include methanol, ethanol, propyl alcohol, dioxane, and acetic acid. In addition, the amount of reaction solvent used is 1 to 1 for the compound [] obtained in the previous step.
50 times the weight, preferably 5 to 10 times the weight.
ｆ工程の脱炭酸反応は、ｅ工程で得られる固形
物を、伝熱媒体中、200〜300℃、好ましくは250
〜280℃で、10分〜10時間、好ましくは30分〜３
時間行う。伝熱媒体としては、ダウサームＡ又は
ナタネ油などが挙げられ、その使用量はｄ工程で
得られる化合物［］に対して１〜50倍重量、好
ましくは２〜10倍重量とする。 In the decarboxylation reaction in step f, the solid obtained in step e is heated at 200 to 300°C, preferably at 250°C in a heat transfer medium.
~280℃, 10 minutes to 10 hours, preferably 30 minutes to 3
Do time. Examples of the heat transfer medium include Dowtherm A or rapeseed oil, and the amount used is 1 to 50 times, preferably 2 to 10 times, the weight of the compound obtained in step d.
なお、ａ工程及びｃ工程において、原料となる
アニリン化合物［］は、下記反応工程式Ａに従
つて製造することができる。 In addition, in the steps a and c, the aniline compound [ ] serving as a raw material can be produced according to the following reaction scheme A.
（反応工程式中、Ｘ及びＹは前記と同意義であ
る。）
作用及び発明の効果
本発明化合物［］は、例えば下記反応工程式
Ｂに従い、抗菌剤として有用な下記一般式［
］の９−ハロゲノ−５−アルキル−８−無置換
乃至三置換ピペラジニル−ベンゾ［ij］キノリジ
ン−２−カルボン酸化合物に誘導され得る。 (In the reaction scheme, X and Y have the same meanings as described above.) Action and Effect of the Invention The compound of the present invention [] can be prepared by the following general formula [], which is useful as an antibacterial agent, according to the following reaction scheme B, for example.
] 9-halogeno-5-alkyl-8-unsubstituted to trisubstituted piperazinyl-benzo[ij]quinolidine-2-carboxylic acid compound.
（反応工程式中、R1は低級アルキル基を、R2
はメチル基又はエチル基を、R3はメチル基、エ
チル基又はメトキシエチル基を夫々表わし、R4
はメチル基、エチル基又はプロピル基を、R5は
メチル基又はエチル基を夫々表わし、R6は水素
原子、炭素数１〜３個のアルキル基又は２−ヒド
ロキシエチル基を表わし、R7及びR8は同一又は
異なつて水素原子、メチル基又はエチル基を夫々
表わし、ここでR8はR7が結合する同一炭素に結
合していてもよく、Ｘ及びＹは同一又は異なつて
フツ素原子又は塩素原子を夫々表わし、X1及び
X3は臭素原子又はヨウ素原子を夫々表わし、X2
は塩素原子又は臭素原子を表わす。）
本発明を実施例をもつて更に説明する。 (In the reaction scheme, R 1 is a lower alkyl group, R 2
represents a methyl group or an ethyl group, R 3 represents a methyl group, an ethyl group or a methoxyethyl group, and R 4
represents a methyl group, an ethyl group, or a propyl group, R 5 represents a methyl group or an ethyl group, R 6 represents a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, or a 2-hydroxyethyl group, R 7 and R 8 are the same or different and represent a hydrogen atom, a methyl group, or an ethyl group, respectively, R 8 may be bonded to the same carbon to which R 7 is bonded, and X and Y are the same or different and represent a fluorine atom. or each represents a chlorine atom, X 1 and
X 3 represents a bromine atom or an iodine atom, respectively, and X 2
represents a chlorine atom or a bromine atom. ) The present invention will be further explained with examples.
実施例 １
（ａ工程）トルエン900mlに、２−ブロモ−５
−クロロ−４−フルオロアニリン449.0ｇ（2.00
モル）、２，２−ジメチル−１，３−ジオキサン
−４，６−ジオン317.0ｇ（2.20モル）及びオル
トギ酸エチル340.8ｇ（2.30モル）を加え、30分
間、加熱還流した。この反応液を氷冷し、析出し
た固形物を濾取し、ついで少量のメタノールで洗
浄し、５−（２−ブロモ−５−クロロ−４−フル
オロアニリノメチレン）−２，２−ジメチル−１，
３−ジオキサン−４，６−ジオンの無色結晶
749.6ｇ（収率99％）を得た。融点は201〜203℃
（分解）であつた。Example 1 (Step a) Add 2-bromo-5 to 900 ml of toluene.
-Chloro-4-fluoroaniline 449.0g (2.00
317.0 g (2.20 mol) of 2,2-dimethyl-1,3-dioxane-4,6-dione and 340.8 g (2.30 mol) of ethyl orthoformate were added thereto, and the mixture was heated under reflux for 30 minutes. The reaction solution was cooled on ice, and the precipitated solid was collected by filtration, washed with a small amount of methanol, and 5-(2-bromo-5-chloro-4-fluoroanilinomethylene)-2,2-dimethyl- 1,
Colorless crystals of 3-dioxane-4,6-dione
749.6g (yield 99%) was obtained. Melting point is 201-203℃
It was (decomposition).
（ｂ工程）上述の結晶605.8ｇ（1.60モル）を、
予め185℃に加熱しておいたダウサームＡの1860
mlに一度に加え、175〜185℃で15分間撹拌した。
この反応液を室温まで冷却したのち更に氷冷し、
これにヘキサン1860mlを注ぎ撹拌した。ついで析
出した固形物を濾取し、少量の酢酸エチルで洗浄
し、８−ブロモ−５−クロロ−６−フルオロ−４
−オキソ−１，４−ジヒドロキノリンの無色結晶
350.8ｇ（収率79％）を得た。融点は230〜232℃
であつた。 (Step b) 605.8 g (1.60 mol) of the above crystals,
Dowtherm A 1860 preheated to 185℃
ml at once and stirred at 175-185°C for 15 minutes.
This reaction solution was cooled to room temperature and then further cooled on ice.
1860 ml of hexane was poured into this and stirred. The precipitated solid was then collected by filtration, washed with a small amount of ethyl acetate, and 8-bromo-5-chloro-6-fluoro-4
-Colorless crystals of oxo-1,4-dihydroquinoline
350.8g (yield 79%) was obtained. Melting point is 230-232℃
It was hot.
1H−核磁気共鳴スペクトル（CF3COOD，
δ）：
7.50（1H，ｄ），8.23（1H，ｄ），8.83（1H，ｄ）
実施例 ２
上述の実施例１において、ａ工程の２−ブロモ
−５−クロロ−４−フルオロアニリンを２−ブロ
モ−４，５−ジクロロアニリン481.9ｇ（2.00モ
ル）に変更した以外はほぼ同様に操作し、８−ブ
ロモ−５，６−ジクロロ−４−オキソ−１，４−
ジヒドロキノリンの無色結晶380.9ｇを得た。融
点は183〜185℃であつた。 1 H-Nuclear Magnetic Resonance Spectrum (CF 3 COOD,
δ): 7.50 (1H, d), 8.23 (1H, d), 8.83 (1H, d) Example 2 In Example 1 above, 2-bromo-5-chloro-4-fluoroaniline in step a was 8-Bromo-5,6-dichloro-4-oxo-1,4-
380.9 g of colorless crystals of dihydroquinoline were obtained. The melting point was 183-185°C.
1H−核磁気共鳴スペクトル（CF3COOD，
δ）：
7.51（1H，ｄ），8.22（1H，ｓ），8.84（1H，ｄ）
実施例 ３
（ａ工程）２−ブロモ−４，５−ジフルオロア
ニリン416.1ｇ（2.00モル）、２，２−ジメチル−
１，３−ジオキサン−４，６−ジオン331.5ｇ
（2.30モル）、オルトギ酸エチル311.2ｇ（2.10モ
ル）及びトルエン850mlを混合し、これを30分間
加熱還流した。得られた反応液を氷冷し、析出し
た固形物を濾取し、ついで少量のエーテルで洗浄
し、５−（２−ブロモ−４，５−ジフルオロアニ
リノメチレン）−２，２−ジメチル−１，３−ジ
オキサン−４，６−ジオンの無色結晶680.9ｇ
（収率94％）を得た。融点は190〜192℃（分解）
であつた。 1 H-Nuclear Magnetic Resonance Spectrum (CF 3 COOD,
δ): 7.51 (1H, d), 8.22 (1H, s), 8.84 (1H, d) Example 3 (Step a) 416.1 g (2.00 mol) of 2-bromo-4,5-difluoroaniline, 2,2 -dimethyl-
1,3-dioxane-4,6-dione 331.5g
(2.30 mol), 311.2 g (2.10 mol) of ethyl orthoformate, and 850 ml of toluene were mixed and heated under reflux for 30 minutes. The resulting reaction solution was ice-cooled, the precipitated solid was collected by filtration, and then washed with a small amount of ether to give 5-(2-bromo-4,5-difluoroanilinomethylene)-2,2-dimethyl- 680.9g colorless crystals of 1,3-dioxane-4,6-dione
(yield 94%). Melting point is 190-192℃ (decomposition)
It was hot.
（ｂ工程）上述の結晶543.3ｇ（1.50モル）を
ダウサームＡの1.6に懸濁し、この懸濁液を撹
拌下に30分間で250℃まで昇温させた。ついでこ
の反応液を氷冷し、これにエーテル1.6を注ぎ
入れ、析出した固形物を濾取した。この固形物を
少量のエーテルで洗浄し、８−ブロモ−５，６−
ジフルオロ−４−オキソ−１，４−ジヒドロキノ
リンの無色結晶234.1ｇ（収率60％）を得た。融
点は212〜214℃であつた。 (Step b) 543.3 g (1.50 mol) of the above crystals were suspended in 1.6 ml of Dowtherm A, and the temperature of this suspension was raised to 250° C. for 30 minutes while stirring. Next, this reaction solution was ice-cooled, 1.6 liters of ether was poured into it, and the precipitated solid was collected by filtration. This solid was washed with a small amount of ether and 8-bromo-5,6-
234.1 g (yield: 60%) of colorless crystals of difluoro-4-oxo-1,4-dihydroquinoline were obtained. The melting point was 212-214°C.
1H−核磁気共鳴スペクトル（CF3COOD，
δ）：
7.47（1H，ｄ），8.23（1H，dd），8.80（1H，ｄ）
実施例 ４
（ｃ工程）２−ブロモ−５−クロロ−４−フル
オロアニリン449.0ｇ（2.00モル）とエトキシメ
チレンマロン酸ジエチル432.5ｇ（2.00モル）と
を混和し、135〜140℃で４時間撹拌し、２−ブロ
モ−５−クロロ−４−フルオロアニリノメチレン
マロン酸ジエチルを生成させた。 1 H-Nuclear Magnetic Resonance Spectrum (CF 3 COOD,
δ): 7.47 (1H, d), 8.23 (1H, dd), 8.80 (1H, d) Example 4 (Step c) 449.0 g (2.00 mol) of 2-bromo-5-chloro-4-fluoroaniline and ethoxy The mixture was mixed with 432.5 g (2.00 mol) of diethyl methylenemalonate and stirred at 135 to 140°C for 4 hours to produce diethyl 2-bromo-5-chloro-4-fluoroanilinomethylenemalonate.
（ｄ工程）この反応生成液を室温まで冷却し、
これにダウサームＡの1.6を注ぎ、265〜270℃
で４時間撹拌した。この反応液を氷冷し、ついで
これにエーテル3.2を加えて撹拌した。析出し
た固形物を濾取し、少量のエーテルで洗浄し、８
−ブロモ−５−クロロ−３−エトキシカルボニル
−６−フルオロ−４−オキソ−１，４−ジヒドロ
キノリンの無色粉末460.1ｇ（収率66％）を得た。 (Step d) Cool this reaction product liquid to room temperature,
Pour 1.6 of Dowtherm A into this and heat to 265-275℃.
The mixture was stirred for 4 hours. This reaction solution was ice-cooled, and then 3.2 liters of ether was added thereto and stirred. The precipitated solid was collected by filtration, washed with a small amount of ether, and
460.1 g (yield: 66%) of colorless powder of -bromo-5-chloro-3-ethoxycarbonyl-6-fluoro-4-oxo-1,4-dihydroquinoline was obtained.
（ｅ工程）上述の粉末348.6ｇ（1.00モル）を
エタノール1400mlに懸濁し、これに20％水酸化ナ
トリウム水溶液720mlを注ぎ、1.5時間、加熱還流
した。この反応液を氷水700mlに注ぎ、濃塩酸に
てPH１に調整した。析出した結晶性粉末を濾取
し、ついで水洗し、乾燥した。 (Step e) 348.6 g (1.00 mol) of the above powder was suspended in 1400 ml of ethanol, and 720 ml of a 20% aqueous sodium hydroxide solution was poured into the suspension, followed by heating under reflux for 1.5 hours. This reaction solution was poured into 700 ml of ice water, and the pH was adjusted to 1 with concentrated hydrochloric acid. The precipitated crystalline powder was collected by filtration, then washed with water and dried.
（ｆ工程）この結晶性粉末の全量をダウサーム
Ａの1000mlに懸濁し、265〜270℃で１時間撹拌し
た。この反応液を氷冷し、エーテル1000mlを加え
て撹拌し、析出した固形物を濾取した。得られた
固形物を少量のエーテルで洗浄し、８−ブロモ−
５−クロロ−６−フルオロ−４−オキソ−１，４
−ジヒドロキノリンの無色結晶246.1ｇ（収率89
％）を得た。この結晶の融点は230〜232℃であ
り、 1H−核磁気共鳴スペクトルは実施例１に記
載した数値と全く一致した。 (Step f) The entire amount of this crystalline powder was suspended in 1000 ml of Dowtherm A and stirred at 265 to 270°C for 1 hour. This reaction solution was ice-cooled, 1000 ml of ether was added and stirred, and the precipitated solid was collected by filtration. The obtained solid was washed with a small amount of ether and 8-bromo-
5-chloro-6-fluoro-4-oxo-1,4
-246.1 g of colorless crystals of dihydroquinoline (yield: 89
%) was obtained. The melting point of this crystal was 230-232°C, and the 1 H-nuclear magnetic resonance spectrum completely matched the values described in Example 1.
実施例 ５
実施例４において、ｃ工程の２−ブロモ−５−
クロロ−４−フルオロアニリンを２−ブロモ−
４，５−ジクロロアニリン481.9ｇ（2.00モル）
に変更した以外はほぼ同様に操作し、８−ブロモ
−５，６−ジクロロ−４−オキソ−１，４−ジヒ
ドロキノリンの無色結晶410.2ｇを得た。この結
晶の融点は183〜185℃であり、 1H−核磁気共鳴
スペクトルは実施例２に記載した数値と全く一致
した。Example 5 In Example 4, 2-bromo-5- in step c
Chloro-4-fluoroaniline to 2-bromo-
4,5-dichloroaniline 481.9g (2.00mol)
The same procedure was repeated except that 410.2 g of colorless crystals of 8-bromo-5,6-dichloro-4-oxo-1,4-dihydroquinoline were obtained. The melting point of this crystal was 183-185°C, and the 1 H-nuclear magnetic resonance spectrum was completely consistent with the values described in Example 2.
実施例 ６
（ｃ工程）２−ブロモ−４，５−ジフルオロア
ニリン416.1ｇ（2.00モル）をエトキシメチレン
マロン酸ジエチル432.5ｇ（2.00モル）に加え、
120〜125℃で６時間撹拌し、２−ブロモ−４，５
−ジフルオロアニリノメチレンマロン酸ジエチル
を生成させた。Example 6 (Step c) 416.1 g (2.00 mol) of 2-bromo-4,5-difluoroaniline was added to 432.5 g (2.00 mol) of diethyl ethoxymethylenemalonate,
Stir at 120-125°C for 6 hours, and add 2-bromo-4,5
- Difluoroanilinomethylene diethyl malonate was produced.
（ｄ工程）この反応生成液を予め270℃に加熱
しておいたダウサームＡの1.5に徐々に注ぎ、
265〜270℃で1.5時間撹拌した。この反応液を氷
冷し、これにエーテル1.5を撹拌下に加え、析
出した固形物を濾取した。この固形物を少量のエ
ーテルで洗浄し、８−ブロモ−５，６−ジフルオ
ロ−３−エトキシカルボニル−４−オキソ−１，
４−ジヒドロキノリンの無色粉末425.1ｇ（収率
64％）を得た。 (Step d) Gradually pour this reaction product liquid into 1.5 ml of Dowtherm A that has been preheated to 270°C.
Stirred at 265-270°C for 1.5 hours. This reaction solution was ice-cooled, 1.5 liters of ether was added to it with stirring, and the precipitated solid was collected by filtration. This solid was washed with a small amount of ether and 8-bromo-5,6-difluoro-3-ethoxycarbonyl-4-oxo-1,
425.1g of colorless powder of 4-dihydroquinoline (yield
64%).
（ｅ工程）得られた粉末332.1ｇ（1.00モル）
をエタノール1400mlに懸濁し、20％水酸化ナトリ
ウム水溶液690mlを加え、２時間加熱還流した。
この反応液を氷水4.5に注ぎ、濃塩酸にてPH１
に調整し、ついで調整液中に析出した結晶性粉末
を濾取、水洗、乾燥した。 (Step e) Obtained powder 332.1g (1.00 mol)
was suspended in 1400 ml of ethanol, 690 ml of 20% aqueous sodium hydroxide solution was added, and the mixture was heated under reflux for 2 hours.
Pour this reaction solution into ice water 4.5, and add concentrated hydrochloric acid to pH 1.
Then, the crystalline powder precipitated in the adjustment solution was collected by filtration, washed with water, and dried.
（ｆ工程）この結晶性粉末の全量をダウサーム
Ａの1000mlに懸濁し、これを265〜270℃で１時間
撹拌した。得られた反応液を氷冷し、これにエー
テル1000mlを撹拌下に加え、析出した固形物を濾
取した。この固形物を少量のエーテルで洗浄し、
８−ブロモ−５，６−ジフルオロ−４−オキソ−
１，４−ジヒドロキノリンの無色結晶226.3ｇ
（収率87％）を得た。この結晶の融点は212〜214
℃であり、 1H−核磁気共鳴スペクトルは実施例
３に記載した数値と全く一致した。 (Step f) The entire amount of this crystalline powder was suspended in 1000 ml of Dowtherm A, and this was stirred at 265 to 270°C for 1 hour. The resulting reaction solution was ice-cooled, 1000 ml of ether was added thereto with stirring, and the precipitated solid was collected by filtration. Wash this solid with a small amount of ether and
8-Bromo-5,6-difluoro-4-oxo-
226.3g colorless crystals of 1,4-dihydroquinoline
(yield 87%). The melting point of this crystal is 212-214
℃, and the 1 H-nuclear magnetic resonance spectrum completely coincided with the values described in Example 3.
実施例 ７
（ａ工程）２−ブロモ−４−クロロ−５−フル
オロアニリン449.0ｇ（2.00モル）、２，２−ジメ
チル−１，３−ジオキサン−４，６−ジオン
317.0ｇ（2.20モル）、オルトギ酸エチル340.8ｇ
（2.30モル）及びエタノール900mlを混合し、これ
を30分間加熱還流した。この反応液を氷冷し、析
出した固形物を濾取し、ついで少量のエタノール
で洗浄し、５−（２−ブロモ−４−クロロ−５−
フルオロアニリノメチレン）−２，２−ジメチル
−１，３−ジオキサン−４，６−ジオンの無色結
晶719.3ｇ（収率95％）を得た。融点は197〜199
℃（分解）であつた。Example 7 (Step a) 449.0 g (2.00 mol) of 2-bromo-4-chloro-5-fluoroaniline, 2,2-dimethyl-1,3-dioxane-4,6-dione
317.0g (2.20mol), ethyl orthoformate 340.8g
(2.30 mol) and 900 ml of ethanol were mixed and heated under reflux for 30 minutes. The reaction solution was cooled on ice, and the precipitated solid was collected by filtration, washed with a small amount of ethanol, and 5-(2-bromo-4-chloro-5-
719.3 g (yield: 95%) of colorless crystals of (fluoroanilinomethylene)-2,2-dimethyl-1,3-dioxane-4,6-dione were obtained. Melting point is 197-199
℃ (decomposition).
（ｂ工程）上述の結晶567.9ｇ（1.50モル）を
ダウサームＡの1700mlに懸濁し、200〜210℃で30
分間撹拌した。この反応液を氷冷し、これにヘキ
サン1700mlを注ぎ撹拌した。ついで析出した固形
物を濾取し少量のエタノールで洗浄し、８−ブロ
モ−６−クロロ−５−フルオロ−４−オキソ−
１，４−ジヒドロキノリンの無色結晶296.9ｇ
（収率72％）を得た。融点は225〜227℃であつた。 (Step b) 567.9 g (1.50 mol) of the above crystals were suspended in 1700 ml of Dowtherm A, and
Stir for a minute. This reaction solution was ice-cooled, and 1700 ml of hexane was poured into it and stirred. The precipitated solid was then collected by filtration and washed with a small amount of ethanol to give 8-bromo-6-chloro-5-fluoro-4-oxo-
296.9g colorless crystals of 1,4-dihydroquinoline
(yield 72%). The melting point was 225-227°C.
1H−核磁気共鳴スペクトル（CF3COOD，
δ）：
7.49（1H，ｄ），8.23（1H，ｄ），8.82（1H，ｄ）
実施例 ８
（ｃ工程）２−ブロモ−４−クロロ−５−フル
オロアニリン449.0ｇ（2.00モル）とエトキシメ
チレンマロン酸ジエチル432.5ｇ（2.00モル）と
を混和し、130〜135℃で５時間撹拌し、２−ブロ
モ−４−クロロ−５−フルオロアニリノメチレン
マロン酸ジエチルを生成させた。 1 H-Nuclear Magnetic Resonance Spectrum (CF 3 COOD,
δ): 7.49 (1H, d), 8.23 (1H, d), 8.82 (1H, d) Example 8 (Step c) 449.0 g (2.00 mol) of 2-bromo-4-chloro-5-fluoroaniline and ethoxy 432.5 g (2.00 moles) of diethyl methylenemalonate were mixed and stirred at 130 to 135°C for 5 hours to produce diethyl 2-bromo-4-chloro-5-fluoroanilinomethylenemalonate.
（ｄ工程）この反応液にダウサームＡの1.6
を注ぎ265〜270℃で３時間撹拌した。この反応液
を氷冷し、ついでこれにエーテル1.6を加えて
撹拌した。析出した固形物を濾取し、少量のエー
テルで洗浄し、８−ブロモ−６−クロロ−３−エ
トキシカルボニル−５−フルオロ−４−オキソ−
１，４−ジヒドロキノリンの無色粉末488.0ｇ
（収率70％）を得た。 (Step d) Add 1.6% of Dowtherm A to this reaction solution.
and stirred at 265-270°C for 3 hours. This reaction solution was cooled with ice, and then 1.6 liters of ether was added and stirred. The precipitated solid was collected by filtration and washed with a small amount of ether to give 8-bromo-6-chloro-3-ethoxycarbonyl-5-fluoro-4-oxo-
1,4-dihydroquinoline colorless powder 488.0g
(yield 70%).
（ｅ工程）上述の粉末348.6ｇ（1.00モル）を
エタノール1400mlに懸濁し、これに20％水酸化ナ
トリウム水溶液700mlを加え２時間加熱還流した。
この反応液を氷水1400mlに注ぎ、濃塩酸にてPH１
に調整した。析出した結晶性粉末を濾取し、つい
で水洗し乾燥した。 (Step e) 348.6 g (1.00 mol) of the above powder was suspended in 1400 ml of ethanol, and 700 ml of a 20% aqueous sodium hydroxide solution was added thereto, followed by heating under reflux for 2 hours.
Pour this reaction solution into 1400ml of ice water, and add concentrated hydrochloric acid to pH 1.
Adjusted to. The precipitated crystalline powder was collected by filtration, then washed with water and dried.
（ｆ工程）この結晶性粉末の全量をダウサーム
Ａの1000mlに懸濁し、265〜270℃で１時間撹拌し
た。この反応液を氷冷し、エーテル1000mlを加え
て撹拌し、析出した固形物を濾取した。得られた
固形物を少量のエーテルで洗浄し、８−ブロモ−
６−クロロ−５−フルオロ−４−オキソ−１，４
−ジヒドロキノリンの無色結晶226.7ｇ（収率82
％）を得た。この結晶の融点は225〜227℃であ
り、 1H−核磁気共鳴スペクトルは実施例７に記
載した数値と全く一致した。 (Step f) The entire amount of this crystalline powder was suspended in 1000 ml of Dowtherm A and stirred at 265 to 270°C for 1 hour. This reaction solution was ice-cooled, 1000 ml of ether was added and stirred, and the precipitated solid was collected by filtration. The obtained solid was washed with a small amount of ether and 8-bromo-
6-chloro-5-fluoro-4-oxo-1,4
-226.7 g of colorless crystals of dihydroquinoline (yield: 82
%) was obtained. The melting point of this crystal was 225-227°C, and the 1 H-nuclear magnetic resonance spectrum was completely consistent with the values described in Example 7.
Claims (1)
子又は塩素原子を夫々表わす。） で示される１，４−ジヒドロ−４−オキソキノリ
ン化合物。 ２ 一般式［］： （式中、Ｘ及びＹは同一又は異なつてフツ素原
子又は塩素原子を夫々表わす。） で示されるアニリン化合物と、２，２−ジメチル
−１，３−ジオキサン−４，６−ジオン及びオル
トギ酸エチルとを反応させ、一般式［］： （式中、Ｘ及びＹは前記と同意義である。） で示される化合物に変換し、この化合物をついで
加熱閉環することを特徴とする一般式［］： （式中、Ｘ及びＹは前記と同意義である。） で示される１，４−ジヒドロ−４−オキソキノリ
ン化合物の製造法。 ３ 一般式［］： （式中、Ｘ及びＹは同一又は異なつてフツ素原
子又は塩素原子を夫々表わす。） で示されるアニリン化合物と、エトキシメチレン
マロン酸ジエチルとを反応させ、一般式［］： （式中、Ｘ及びＹは前記と同意義である。） で示される化合物を生成し、この化合物を加熱閉
環して一般式［］： （式中、Ｘ及びＹは前記と同意義である。） で示される化合物に変換し、ついでこの化合物を
加水分解し、最後に脱炭酸することを特徴とする
一般式［］： （式中、Ｘ及びＹは前記と同意義である。） で示される１，４−ジヒドロ−４−オキソキノリ
ン化合物の製造法。[Claims] 1 General formula []: (In the formula, X and Y are the same or different and represent a fluorine atom or a chlorine atom, respectively.) A 1,4-dihydro-4-oxoquinoline compound represented by the following. 2 General formula []: (In the formula, X and Y are the same or different and represent a fluorine atom or a chlorine atom, respectively.) An aniline compound represented by: 2,2-dimethyl-1,3-dioxane-4,6-dione and orthoformic acid By reacting with ethyl, the general formula []: (In the formula, X and Y have the same meanings as above.) The general formula [] is characterized by converting it into a compound represented by the formula, and then ring-closing this compound by heating: (In the formula, X and Y have the same meanings as above.) A method for producing a 1,4-dihydro-4-oxoquinoline compound represented by the following. 3 General formula []: (In the formula, X and Y are the same or different and represent a fluorine atom or a chlorine atom, respectively.) The aniline compound represented by the formula is reacted with diethyl ethoxymethylene malonate, and the general formula []: (In the formula, X and Y have the same meanings as above.) A compound represented by the formula is produced, and this compound is ring-closed by heating to give the general formula []: (In the formula, X and Y have the same meanings as above.) A general formula [] characterized by converting into a compound represented by, then hydrolyzing this compound, and finally decarboxylating it: (In the formula, X and Y have the same meanings as above.) A method for producing a 1,4-dihydro-4-oxoquinoline compound represented by the following.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61-276684 | 1986-11-21 | ||
| JP27668486 | 1986-11-21 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS63239269A JPS63239269A (en) | 1988-10-05 |
| JPH046707B2 true JPH046707B2 (en) | 1992-02-06 |
Family
ID=17572877
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62290757A Granted JPS63239269A (en) | 1986-11-21 | 1987-11-19 | 1,4-dihydro-4-oxoquinoline compound and its production |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS63239269A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE223901T1 (en) * | 1994-03-01 | 2002-09-15 | Ishihara Sangyo Kaisha | METHOD FOR PRODUCING 5,7 DICHLORO-4-HYDROXYQUINOLINE |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5758668A (en) * | 1980-07-28 | 1982-04-08 | Dynamit Nobel Ag | Manufacture of quinoline, naphthyridine and other nitrogen-bi-heterocyclic compound |
-
1987
- 1987-11-19 JP JP62290757A patent/JPS63239269A/en active Granted
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5758668A (en) * | 1980-07-28 | 1982-04-08 | Dynamit Nobel Ag | Manufacture of quinoline, naphthyridine and other nitrogen-bi-heterocyclic compound |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS63239269A (en) | 1988-10-05 |
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