JPS63239269A - 1,4-dihydro-4-oxoquinoline compound and its production - Google Patents
1,4-dihydro-4-oxoquinoline compound and its productionInfo
- Publication number
- JPS63239269A JPS63239269A JP62290757A JP29075787A JPS63239269A JP S63239269 A JPS63239269 A JP S63239269A JP 62290757 A JP62290757 A JP 62290757A JP 29075787 A JP29075787 A JP 29075787A JP S63239269 A JPS63239269 A JP S63239269A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- compound
- general formula
- formulas
- 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.)
- Granted
Links
- -1 1,4-dihydro-4-oxoquinoline compound Chemical class 0.000 title claims description 21
- 238000004519 manufacturing process Methods 0.000 title claims description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 21
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 7
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 claims abstract description 7
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 6
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 6
- 125000001153 fluoro group Chemical group F* 0.000 claims description 5
- 238000010438 heat treatment Methods 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims 8
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 abstract description 10
- 238000006798 ring closing metathesis reaction Methods 0.000 abstract description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 abstract 1
- 230000000844 anti-bacterial effect Effects 0.000 abstract 1
- 230000000694 effects Effects 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- GXHFUVWIGNLZSC-UHFFFAOYSA-N meldrum's acid Chemical compound CC1(C)OC(=O)CC(=O)O1 GXHFUVWIGNLZSC-UHFFFAOYSA-N 0.000 abstract 1
- 239000010499 rapseed oil Substances 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 30
- 238000006243 chemical reaction Methods 0.000 description 23
- 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
- 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
- 239000000203 mixture Substances 0.000 description 12
- 239000000843 powder Substances 0.000 description 12
- 238000002844 melting Methods 0.000 description 11
- 230000008018 melting Effects 0.000 description 11
- 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 10
- 239000007810 chemical reaction solvent Substances 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 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
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- LTMHNWPUDSTBKD-UHFFFAOYSA-N diethyl 2-(ethoxymethylidene)propanedioate Chemical compound CCOC=C(C(=O)OCC)C(=O)OCC LTMHNWPUDSTBKD-UHFFFAOYSA-N 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 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 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- OPOFPVOALIOZBR-UHFFFAOYSA-N 1-fluoroquinolin-4-one Chemical compound C1=CC=C2N(F)C=CC(=O)C2=C1 OPOFPVOALIOZBR-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-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
- 239000005457 ice water Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 3
- ROBKVGDBQLURAF-UHFFFAOYSA-N 1,4-dihydroquinoline Chemical compound C1=CC=C2CC=CNC2=C1 ROBKVGDBQLURAF-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 compound [Br] WKBOTKDWSSQWDR-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
- 239000007864 aqueous solution Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 238000006114 decarboxylation reaction Methods 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
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 230000003595 spectral effect Effects 0.000 description 2
- DTQVDTLACAAQTR-DYCDLGHISA-N trifluoroacetic acid-d1 Chemical compound [2H]OC(=O)C(F)(F)F DTQVDTLACAAQTR-DYCDLGHISA-N 0.000 description 2
- IRFSXVIRXMYULF-UHFFFAOYSA-N 1,2-dihydroquinoline Chemical compound C1=CC=C2C=CCNC2=C1 IRFSXVIRXMYULF-UHFFFAOYSA-N 0.000 description 1
- 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
- BUTIDJREEDINSI-UHFFFAOYSA-N 2-bromo-4,5-difluoroaniline Chemical compound NC1=CC(F)=C(F)C=C1Br BUTIDJREEDINSI-UHFFFAOYSA-N 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- LLWADFLAOKUBDR-UHFFFAOYSA-N 2-methyl-4-chlorophenoxybutyric acid Chemical compound CC1=CC(Cl)=CC=C1OCCCC(O)=O LLWADFLAOKUBDR-UHFFFAOYSA-N 0.000 description 1
- BYZXOYSEYWCLOK-UHFFFAOYSA-N 6-fluoro-1h-quinolin-4-one Chemical compound C1=C(F)C=C2C(O)=CC=NC2=C1 BYZXOYSEYWCLOK-UHFFFAOYSA-N 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
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 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
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- BQHDXNZNSPVVKB-UHFFFAOYSA-N diethyl 2-methylidenepropanedioate Chemical compound CCOC(=O)C(=C)C(=O)OCC BQHDXNZNSPVVKB-UHFFFAOYSA-N 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 229910052740 iodine 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
- 239000002994 raw material Substances 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
Landscapes
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
- Quinoline Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
星東上五皿里方1
本発明は、下記一般式[■]:
(式中、X及びYは同−又は異なってフッ素原子又は塩
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[I]」という)及びその
製造法に関する。[Detailed Description of the Invention] Hoshitojo Gosara Rikata 1 The present invention is represented by 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.) The present invention relates to a 1,4-dihydro-4-oxoquinoline compound (hereinafter simply referred to as "the compound of the present invention [I]") and a method for producing the same.
嚢米Ω返ヨ
本発明化合物[I]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おる。The compound [I] 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.
明が 決しようとする。l 慮
本発明化合物[I]は、本発明者らの一部はかにより開
発中の新規な9−ハロゲン−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
。Ming tries to decide. l Considered, the compound [I] of the present invention is a novel 9-halogen-5-alkyl-8-unsubstituted to trisubstituted piperazinyl-benzo[ij]quinolidine- which is currently being developed by the present inventors.
It is useful as an intermediate in the production of 2-carboxylic acid antibacterial agents.
同 点を解決するための≦
本発明化合物[I]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−シ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。In order to solve the same point, the compound [I] of the present invention has the following general formula [■]: (wherein, X
and Y have the same meanings as above. ) and 2,2-dimethyl-1,3-dioxane-4,
6-Sion and ethyl orthoformate are reacted to form the following general formula [■]: (wherein, X and Y have the same meanings as above).
)で示される化合物に変換しく以下a工程という)、こ
の化合物[III]をついで加熱閉環する(以下す工程
という)ことにより製造することができる。) can be produced by converting the compound [III] into a compound represented by (hereinafter referred to as step a), and then subjecting this compound [III] to ring closure by heating (hereinafter referred to as step a).
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’Cで、15分〜10時間
、好ましくは30分〜5時間行う。The reaction in step a is carried out without a solvent or in a reaction solvent at a concentration of 20 to 110
C., preferably 50 to 110'C, for 15 minutes to 10 hours, preferably 30 minutes to 5 hours.
反応)容媒としては、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[n]に対する使用量は、2.2−ジメチル−1,
3−ジオキサン−4,6−シ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。Examples of the reaction medium include methanol, ethanol, propyl alcohol, benzene, toluene, and a mixture of two or more thereof. The amount used for the aniline compound [n] is 2,2-dimethyl-1,
Both 3-dioxane-4,6-sion and ethyl orthoformate are used in 1 to 6 moles, preferably 1 to 3 moles. Similarly, the reaction solvent is 0.5 to 20 times the weight, preferably 1
~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[1
]を、伝熱媒体中、120〜300℃、好ましくは17
0〜260℃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(ビフェニル
とジフェ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[DI]に対して1〜
50@重量、好ましくは2〜in重量とする。The heating ring-closing reaction in step b is the compound [1] obtained in step a.
] in a heat transfer medium at 120-300°C, preferably 17
It is carried out at 0 to 260°C for 2 minutes to 5 hours, preferably 5 minutes to 2 hours. Examples of the heat transfer medium include Dowtherm A (a mixture of biphenyl and diphenyl ether) or rapeseed oil, and the amount used is 1 to 100% of the compound [DI].
50@wt, preferably 2-in.wt.
また、本発明化合物[I]は、前記一般式[II]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[IV]:(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
しく以下C工程という)、この化合物[IV]を加熱閉
環して下記一般式[V](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く以下C工程と
いう)、ついでこの化合物[V]を加水分解しく以下C
工程という)、最後に脱炭酸する(以下f工程という)
ことによっても製造することができる。In addition, the compound [I] of the present invention can be obtained by reacting the aniline compound represented by the general formula [II] with diethyl ethoxymethylenemalonate, and producing the following general formula [IV]: (wherein, X and Y are the same as above. (hereinafter referred to as C step), this compound [IV] is ring-closed by heating to form the following general formula [V] (wherein, X and Y have the same meanings as above). (hereinafter referred to as C step), and then this compound [V] is hydrolyzed (hereinafter referred to as C step).
process), and finally decarboxylation (hereinafter referred to as f process)
It can also be manufactured by
C工程の反応は、無溶媒又は反応溶媒中、20〜190
’C1好ましくは60〜150’C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。The reaction in step C is carried out without a solvent or in a reaction solvent at a reaction temperature of 20 to 190
'C1 preferably at 60-150'C for 1-10 hours,
Preferably it is carried out for 2 to 6 hours. As a reaction solvent, methanol, ethanol, propyl alcohol, benzene, toluene, ethyl acetate, N.
N−ジメチルホルムアミドもしくはジメチルスル小キシ
ド又はこれらの二種以上からなる混合液が挙げられる。Examples include N-dimethylformamide, dimethyl sulfide, or a mixture of two or more thereof.
エトキシメチレンマロン酸ジエチルは、アニリン化合物
[II]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[n]に対して1〜50倍重量
、好ましくは3〜20倍重量とする。Diethyl ethoxymethylene malonate is used in a molar amount of 1 to 5 times, preferably 1 to 2 times, the amount of aniline compound [II]. When a reaction solvent is used, the amount of the reaction solvent used is 1 to 50 times, preferably 3 to 20 times the weight of the aniline compound [n].
C工程の加熱閉環反応は、C工程で得られる化合物[I
V]ヲ、伝熱媒体中、200〜3QO℃、好ましくは2
50〜280’Cで、10分〜10時間、好ましくは3
0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[I
V]に対して1〜50(8重量、好ましくは2〜10倍
重量とする。The heating ring-closing reaction in Step C is performed on the compound [I
V] 200-3QO℃ in a heat transfer medium, preferably 2
50-280'C, 10 minutes-10 hours, preferably 3
Do this for 0 minutes to 3 hours. Examples of the heat transfer medium include Dowtherm A or rapeseed oil, and the amount used is determined by the amount of the compound [I
V] to 1 to 50 (8 weight, preferably 2 to 10 times the weight).
C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[V]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 C 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 acids include dilute hydrochloric acid or dilute sulfuric acid.
Examples of the alkali include aqueous solutions of sodium hydroxide and potassium hydroxide, respectively. Examples of the reaction solvent include methanol, ethanol, propyl alcohol, dioxane, and acetic acid. The amount of the reaction solvent to be used is 1 to 50 times, preferably 5 to 10 times the weight of the compound [V] obtained in the previous step.
f工程の脱炭酸反応は、C工程で得られる固形物を、伝
熱媒体中、200〜300℃、好ましくは250〜28
0℃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C工程で得られる化合物[
V]に対して1〜50倍重口、好ましくは2〜10(8
重量とする。In the decarboxylation reaction in step f, the solid obtained in step C is heated at 200 to 300°C, preferably 250 to 28°C, in a heat transfer medium.
The treatment is carried out at 0°C for 10 minutes to 10 hours, preferably 30 minutes to 3 hours. Examples of the heat transfer medium include Dowtherm A or rapeseed oil, and the amount used is determined by the amount of the compound obtained in step C [
V], 1 to 50 times heavier, preferably 2 to 10 times heavier (8
Weight.
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[II]は、下記反応工程式Aに従って製造する
ことができる。In addition, in step a and step C, the aniline compound [II] serving as a raw material can be produced according to the following reaction scheme A.
反応工程式A
(アニリン化合物[■]〉
(反応工程式中、X及びYは前記と同意義でおる。)
11及l旦皿り皇1
本発明化合物[I]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[XIII]の9−ハ
ロゲン−5−アルキル−8−無置換乃至三置換ピペラジ
ニル−ベンゾ[ijlキノリジン−2−カルボン酸化合
物に誘導され得る。Reaction Scheme A (Aniline Compound [■]> (In the Reaction Scheme, X and Y have the same meanings as above.) According to B, a 9-halogen-5-alkyl-8-unsubstituted to trisubstituted piperazinyl-benzo[ijlquinolidine-2-carboxylic acid compound of the following general formula [XIII] useful as an antibacterial agent can be derived.
(以下余白)
(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、R及びR8は
同−又は異なって水素原子、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−又は異なってフッ素原
子又は塩素原子を夫々表わし、×1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って更に説明する
。(Left below) (In the reaction scheme, R1 represents a lower alkyl group, R2 represents a methyl group or ethyl group, R3 represents a methyl group, ethyl group or methoxyethyl group, and R4 represents a methyl group, ethyl group or propyl group. R5 represents a methyl group or an ethyl group, R6 represents a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, or a 2-hydroxyethyl group, and R and R8 are the same or different and represent a hydrogen atom, a methyl group, or ethyl group, respectively, where R8 may be bonded to the same carbon to which R7 is bonded, X and Y are the same or different and represent a fluorine atom or a chlorine atom, respectively, and x1 and X3 are bromine or an iodine atom, respectively, and X2 represents a chlorine atom or a bromine atom.) The present invention will be further explained with reference to Examples.
実施例1
(a工程) 1〜ルエン900dに、2−ブロモ−5−
クロロ−4−フルオロアニリン449.0Ij(2,0
0モル)、2,2−ジメチル−1゜3−ジオキサン−4
,6−ジオン317.0び(2,20モル)及びオルト
ギ酸エチル340. EEF(2,30モル)を加え、
30分間、加熱還流した。Example 1 (Step a) 1 to 900d of toluene, 2-bromo-5-
Chloro-4-fluoroaniline 449.0Ij (2,0
0 mol), 2,2-dimethyl-1゜3-dioxane-4
, 317.0 of 6-dione (2.20 mol) and 340.0 of ethyl orthoformate. Add EEF (2,30 mol),
The mixture was heated to reflux for 30 minutes.
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201〜2
03℃(分解)でおった。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- 749.6 g (yield: 99%) of colorless crystals of 1,3-dioxane-4,6-dione were obtained. Melting point is 201-2
03°C (decomposition).
(b工程) 上述の結晶605.8tj(1,60モル
)を、予め185°Cに加熱しておいたダウサームAの
1860dに一度に加え、175〜185℃で15分間
撹拌した。この反応液を空温まで冷却したのち更に氷冷
し、これにベキサン1860戒を注ぎ撹拌した。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350.8y (
収率79%)を得た。融点は230〜232℃でおった
。(Step b) 605.8tj (1.60 mol) of the above crystals were added at once to Dowtherm A 1860d which had been heated to 185°C in advance, and stirred at 175-185°C for 15 minutes. This reaction solution was cooled to air temperature and then further cooled on ice, and Bexane 1860 was poured into it and stirred. Then, the precipitated solid was collected by filtration, washed with a small amount of ethyl acetate,
8-bromo-5-chloro-6-fluoro-4-oxo-
Colorless crystals of 1,4-dihydroquinoline 350.8y (
A yield of 79% was obtained. The melting point was 230-232°C.
1日−核磁気共鳴スペクトル、(CF3 GOOD。1st - Nuclear magnetic resonance spectrum, (CF3 GOOD.
δ)ニ
ア、50(IH,d)、 8.23(1N、d)、 8
.83(IH,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−ブロモー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380.93を得た。融点は183〜185℃でめっ
た。δ) Near, 50 (IH, d), 8.23 (1N, d), 8
.. 83 (IH, d) Example 2 In the above Example 1, 2-bromo-5-chloro-4-fluoroaniline in step a was replaced with 481.9 g (2,00 mol) of 2-bromo-4,5-dichloroaniline. The procedure was carried out in almost the same manner except that 380.93 of a colorless crystal of 8-bromo-5,6-dichloro-4-oxo-1,4-dihydroquinoline was obtained. The melting point was 183-185°C.
1H’t<’a気共15スベ’) トJI/ (CF3
C00D。1H't<'a ki 15 sube') トJI/ (CF3
C00D.
δ)ニ
ア、51(IH,d)、 8.22(IH,S)、 8
.84(IH,d)X思■旦
(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−シオン331.5g(2,
30モル)、オルトギ酸エチル311.2g (2,1
0モル)及びトルエン850mAを混合し、これを30
分間加熱還流した。δ) Near, 51 (IH, d), 8.22 (IH, S), 8
.. 84 (IH, d)
,3-dioxane-4,6-sion 331.5g (2,
30 mol), ethyl orthoformate 311.2 g (2,1
0 mole) and 850 mA of toluene were mixed, and this was mixed with 30
The mixture was heated to reflux for a minute.
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6
80.99 (収率94%)を得た。融点は190〜1
92℃(分解)であった。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-1,3-dioxane-4°6-dione colorless crystals 6
80.99 (yield 94%) was obtained. Melting point is 190-1
The temperature was 92°C (decomposed).
(b工程) 上述の結晶543.39 (1,50モル
)をダウサームAの1.6.l!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1.6Nを注ぎ入
れ、析出した固形物を濾取した。(Step b) The above crystal 543.39 (1,50 mol) was mixed with 1.6 mol of Dowtherm A. l! The temperature of this suspension was raised to 250° C. for 30 minutes while stirring. Next, this reaction solution was cooled with ice, 1.6N of ether was poured into it, and the precipitated solid was collected by filtration.
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234.1tj(収率60%)を得た。This solid was washed with a small amount of ether and 8-bromo-5
, 234.1tj (yield 60%) of colorless crystals of 6-difluoro-4-oxo-1,4-dihydroquinoline were obtained.
融点は212〜214°Cでめった。The melting point was 212-214°C.
1日−核磁気共鳴スペクトル(CF3COOD。1 day - Nuclear magnetic resonance spectrum (CF3COOD.
δ) ニ
ア、47(1M、d)、 8.23(IH,dd)、
8.80(IH,d)X塵■A
(C工程) 2−ブロモ−5−クロロ−4−フルオロア
ニリン449.Oび(2,00モル)とエトキシメチレ
ンマロン酸ジエチル432.59(2,00モル〉とを
混和し、135〜140℃で4時間撹拌し、2−ブロモ
ー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。δ) Near, 47 (1M, d), 8.23 (IH, dd),
8.80 (IH, d) Obi (2,00 mol) and 432.59 (2,00 mol) diethyl ethoxymethylenemalonate were mixed and stirred at 135 to 140°C for 4 hours to form 2-bromo-5-chloro-4-fluoroanilino. Diethyl methylenemalonate was produced.
(d工程) この反応生成液を空温まで冷却し、これに
ダウサームAの1.61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3.2.1!を加えて撹拌した。(Step d) This reaction product liquid was cooled to air temperature, 1.61 of Dowtherm A was poured into it, and 4
Stir for hours. This reaction solution was cooled on ice, and then 3.2.1! of ether was added to it. was added and stirred.
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460.19(収率66%)を得た。The precipitated solid was collected by filtration, washed with a small amount of ether, and
-bromo-5-chloro-3-ethoxycarbonyl-6-
460.19 (yield: 66%) of colorless powder of fluoro-4-oxo-1,4-dihydroquinoline was obtained.
(C工程) 上述の粉末348.6ff (1,00−
Eル)をエタノール1400dに懸濁し、これに20%
水酸化ナトリウム水溶液720rniを注ぎ、1.5時
間、加熱還流した。この反応液を氷水700dに注ぎ、
濃塩酸にてpH’lに調整した。(Step C) 348.6ff of the above powder (1,00-
Suspend Ele) in 1400d of ethanol and add 20%
720 rni of sodium hydroxide aqueous solution was poured into the mixture, and the mixture was heated under reflux for 1.5 hours. Pour this reaction solution into 700 d of ice water,
The pH was adjusted to 1 with concentrated hydrochloric acid.
析出した結晶性粉末を濾取し、ついで水洗し、乾燥した
。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1
0100O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1000m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°Cであり、′H−核磁気共
鳴スベクトルは実施例1に記載した数値と全く一致した
。(Step f) The entire amount of this crystalline powder is
0100O and stirred at 265-270°C for 1 hour. The reaction solution was ice-cooled, 1000 ml of ether was added and stirred, and the precipitated solid was collected by filtration. The resulting solid was washed with a small amount of ether to give 8-bromo-5-chloro-
246.1 g (yield: 89%) of colorless crystals of 6-fluoro-4-oxo-1,4-dihydroquinoline were obtained. The melting point of this crystal was 230-232°C, and the 'H-Nuclear Magnetic Resonance Svector was completely consistent with the value described in Example 1.
X血■支
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481.9SJ (2,00モル)に変更した
以外(よほぼ同様に操作し、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410.29を得た。In Example 4, 2-bromo-5-chloro-
8-Bromo-5,6-dichloro-4-oxo- 410.29 of a colorless crystal of 1,4-dihydroquinoline was obtained.
この結晶の融点は183〜185℃でおり、′H−核磁
気共鳴スベクトルは実施例2に記載した数値と全く一致
した。The melting point of this crystal was 183-185°C, and the 'H-nuclear magnetic resonance spectral value was completely consistent with the value described in Example 2.
割O坦
(C工程)2−ブロモ−4,5−ジフルオロアニリン4
16.1g(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、12
0〜125℃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。Split O-flat (C step) 2-bromo-4,5-difluoroaniline 4
16.1 g (2,00 mol) was added to 432.5 g (2,00 mol) of diethyl ethoxymethylenemalonate, and 12
The mixture was stirred at 0 to 125° C. for 6 hours to produce diethyl 2-bromo-4,5-difluoroanilinomethylenemalonate.
(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1.5fIに徐々に注ぎ、265
〜270℃で1.5時間撹拌した。(Step d) This reaction product liquid was gradually poured into 1.5 fI of Dowtherm A which had been heated to 270°C in advance.
Stir at ~270°C for 1.5 hours.
この反応液を氷冷し、これにエーテル1.5g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。This reaction solution was ice-cooled, 1.5 g of ether was added thereto with stirring, and the precipitated solid was collected by filtration. This solid was washed with a small amount of ether to obtain 425.1 g (yield: 64%) of a colorless powder of 8-bromo-5,6-difluoro-3-ethoxycarbonyl-4-oxo-1,4-dihydroquinoline. Ta.
(C工程) 得られた粉末332.1 g(1,00モ
ル)をエタノール1400m1に懸濁し、20%水酸化
ナトリウム水溶液690rriiを加え、2時間加熱還
流した。この反応液を氷水4.51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 C) 332.1 g (1,00 mol) of the obtained powder was suspended in 1400 ml of ethanol, 690 rrii of a 20% aqueous sodium hydroxide solution was added, and the mixture was heated under reflux for 2 hours. This reaction solution was poured into ice water (4.5%), adjusted to pH 1 with concentrated hydrochloric acid, and then the crystalline powder precipitated in the adjusted 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1
000rIJ1に懸濁し、これを265〜270℃で1
時間撹拌した。得られた反応液を水冷し、これにエーテ
ル1000rr11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226.39(収率87%
)を得た。この結晶の融点は212〜214℃であり、
′H−核磁気共鳴スベクトルは実施例3に記載した数値
と全く一致した。(Step f) The entire amount of this crystalline powder is
000rIJ1 and incubate it at 265-270°C.
Stir for hours. The resulting reaction solution was cooled with water, 1,000 rr 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
-bromo-5,6-difluoro-4-oxo-1,4-
Colorless crystals of dihydroquinoline 226.39 (yield 87%)
) was obtained. The melting point of this crystal is 212-214°C,
The 'H-Nuclear Magnetic Resonance vector was completely consistent with the values described in Example 3.
釆厘恩l
(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)、2゜2−ジメチル
−1,3−ジオキサン−4,6−シオン317.0!?
(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900威を混合し、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719.39(収率95%)
を得た。融点は197〜199℃(分解)であった。(Step C) 449.0 g (2,00 mol) of 2-bromo-4-chloro-5-fluoroaniline, 317.0 g (2,00 mol) of 2゜2-dimethyl-1,3-dioxane-4,6-sion ! ?
(2.20 mol), ethyl orthoformate 340.8 g (
2.30 moles) and 900 moles of ethanol were mixed, and the mixture was heated under reflux for 30 minutes. The reaction solution was cooled on ice, the precipitated solid was collected by filtration, and then washed with a small amount of ethanol.
5-(2-bromo-4-chloro-5-fluoroanilinomethylene)-2,2-dimethyl-1,3-dioxane-
Colorless crystals of 4,6-dione 719.39 (yield 95%)
I got it. The melting point was 197-199°C (decomposed).
(b工程)上述の結晶567.99 (1,50モル)
をダウサームAの1700d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1700d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.(1(収率72%)を得
た。融点は225〜227℃でおった。(Step b) Above crystal 567.99 (1,50 mol)
suspended in Dowtherm A 1700d, 200-210
Stirred at ℃ for 30 minutes. This reaction solution was ice-cooled, and 1700 d of hexane was poured into it and stirred. Then, the precipitated solid was collected by filtration and washed with a small amount of ethanol to obtain 8-bromo-6.
Colorless crystals of -chloro-5-fluoro-4-oxo-1,4-dihydroquinoline 296. (1 (yield 72%)) The melting point was 225-227°C.
1日−核磁気共鳴スペクトル(CF3COOD。1 day - Nuclear magnetic resonance spectrum (CF3COOD.
δ)ニ
ア、49(IH,d)、8.23(1?l、d)、8.
82(IH,d)1思U
(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432.5ff(2,00モル)とを
混和し、130〜135℃で5時間撹拌し、2−ブロモ
ー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。δ) Near, 49 (IH, d), 8.23 (1?l, d), 8.
82 (IH, d) 1 U (Step C) 449.0 g (2,00 mol) of 2-bromo-4-chloro-5-fluoroaniline and 432.5 ff (2,00 mol) of diethyl ethoxymethylenemalonate. were mixed and stirred at 130-135°C for 5 hours to produce diethyl 2-bromo4-chloro-5-fluoroanilinomethylenemalonate.
(C工程)この反応液にダウサームAの1.61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1.61を加えて撹拌した。(Step C) 1.61 of Dowtherm A was poured into this reaction solution and stirred at 265 to 270°C for 3 hours. This reaction solution was ice-cooled, and then 1.61 g of ether was added thereto and stirred.
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。The precipitated solid was collected by filtration, washed with a small amount of ether, and
-bromo-6-chloro-3-ethoxycarbonyl-5-
488.0 g (yield 70%) of colorless powder of fluoro-4-oxo-1,4-dihydroquinoline was obtained.
(e工程)上述の粉末348.6y (1,00モル)
をエタノール1400mに懸濁し、これに20%水駿化
ナトリウム水溶液700m1を加え2時間加熱還流した
。この反応液を氷水14001dに注ぎ、濃塩酸にてp
I−11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) Above powder 348.6y (1,00 mol)
was suspended in 1,400 ml of ethanol, 700 ml of a 20% aqueous sodium hydroxide solution was added thereto, and the mixture was heated under reflux for 2 hours. This reaction solution was poured into ice water 14001d, and the solution was purified with concentrated hydrochloric acid.
Adjusted to I-11. 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10
100O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1000d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、′H−核磁気共鳴スベ
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 total amount of this crystalline powder is 10% of Dowtherm A.
The mixture was suspended at 100O and stirred at 265-270°C for 1 hour. This reaction solution was ice-cooled, 1000 d of ether was added and stirred, and the precipitated solid was collected by filtration. The resulting solid was washed with a small amount of ether to give 8-bromo-6-chloro-5-
226.7 g (yield: 82%) of colorless crystals of fluoro-4-oxo-1,4-dihydroquinoline were obtained. The melting point of this crystal was 225 to 227°C, and the 'H-nuclear magnetic resonance spectral value was completely consistent with the value described in Example 7.
Claims (3)
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。(1) General formula [I]: ▲There are mathematical formulas, chemical formulas, tables, etc.▼[I] (In the formula, X and Y are the same or different and represent a fluorine atom or a chlorine atom, respectively.) 1, 4 represented by -dihydro-4-oxoquinoline compound.
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[III]:▲数式、化学式、表等
があります▼[III] (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[ I ]:▲数式、化学式、表等が
あります▼[ I ] (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
。(2) General formula [II]: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ [II] (In the formula, X and Y are the same or different and represent a fluorine atom or a chlorine atom, respectively.) ,2,2-dimethyl-1,
By reacting 3-dioxane-4,6-dione and ethyl orthoformate, the general formula [III]: ▲ There are numerical formulas, chemical formulas, tables, etc. ▼ [III] (In the formula, X and Y have the same meanings as above. General formula [I]: ▲There are mathematical formulas, chemical formulas, tables, etc.▼[I] (In the formula, X and Y are A method for producing a 1,4-dihydro-4-oxoquinoline compound shown in (same meaning as above).
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[IV]:▲数式、化学
式、表等があります▼[IV] (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[V
]: ▲数式、化学式、表等があります▼[V] (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[ I ]: ▲数式、化学式、表等があります▼[ I ] (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) General formula [II]: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ [II] (In the formula, X and Y are the same or different and represent a fluorine atom or a chlorine atom, respectively.) , and ethoxymethylene diethyl malonate to form a compound represented by the general formula [IV]: ▲Mathematical formula, chemical formula, table, etc.▼[IV] (wherein, X and Y have the same meanings as above) This compound is ring-closed by heating to form the general formula [V
]: ▲There are mathematical formulas, chemical formulas, tables, etc.▼[V] (In the formula, General formula [I] characterized by carbonation: ▲There are mathematical formulas, chemical formulas, tables, etc.▼1,4-dihydro represented by [I] (wherein, X and Y have the same meanings as above) - A method for producing a 4-oxoquinoline compound.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP27668486 | 1986-11-21 | ||
JP61-276684 | 1986-11-21 |
Publications (2)
Publication Number | Publication Date |
---|---|
JPS63239269A true JPS63239269A (en) | 1988-10-05 |
JPH046707B2 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) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1995023787A1 (en) * | 1994-03-01 | 1995-09-08 | Ishihara Sangyo Kaisha, Ltd. | Process 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 |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1995023787A1 (en) * | 1994-03-01 | 1995-09-08 | Ishihara Sangyo Kaisha, Ltd. | Process for producing 5,7-dichloro-4-hydroxyquinoline |
Also Published As
Publication number | Publication date |
---|---|
JPH046707B2 (en) | 1992-02-06 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JPH0148911B2 (en) | ||
CN114292231A (en) | 2-methyl-8-substituent-quinoline and preparation method thereof | |
JP2004500324A (en) | Novel synthesis and crystallization of piperazine ring-containing compounds | |
GB2031934A (en) | Chromogenic pyridine compounds | |
US2797218A (en) | Cinnoline derivatives | |
JPH02215750A (en) | Preparation of 2,6-dichlorophenylaminobenzeneacetic acid derivative | |
JPS63239269A (en) | 1,4-dihydro-4-oxoquinoline compound and its production | |
JPS6143339B2 (en) | ||
US4216340A (en) | Preparation of 5-(2,4-difluorophenyl)salicylic acid and derivatives | |
JP2788221B2 (en) | Novel method for producing quinoline-2,3-dicarboxylic acid | |
AU2003249262B2 (en) | Process for the preparation of imidazo(1,2-a)pyridine-3-acetamides | |
JPH0217161A (en) | Production of tris (2-cyanoethyl) amine | |
CN106167469A (en) | A kind of method of synthesis 2 amino 4,6 dihydroxy-pyrimidines | |
US4256639A (en) | Process for the synthesis of isatin derivatives | |
US6465653B2 (en) | Noncatalyzed synthesis of 4-hydroxyquinolines and/or tautomers thereof | |
JPH0742300B2 (en) | Amifloxacin intermediate | |
JPH0330596B2 (en) | ||
KR930003757B1 (en) | The producing method of substituted beta phenyl acrylic acid | |
JPS58172389A (en) | Manufacture of 1,2,5,6-tetrahydro-4-h- pyrrolo(3,2,1-ij)-quinolin-4-one and novel 5-halogen-1,2,3-(1,2-dihydropyrrolo)-4-quinolone as intermediate product | |
CA1081251A (en) | Process for the preparation of 3-alkyl-cyclopentane-1, 2-diones, and itermediates therefor | |
JPS593995B2 (en) | 2- Styryl -3,1- Benzoxazine -4- | |
JPS5859971A (en) | Preparation of 3-hydroxyquinophthalone compound | |
JPS5855187B2 (en) | Basic dye manufacturing method | |
JPH06135937A (en) | Production of 5,5-disubstituted hydantoin | |
JPH083045B2 (en) | Process for producing dichlorosilicon naphthalocyanine |