JPH0482138B2 - - Google Patents
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- Publication number
- JPH0482138B2 JPH0482138B2 JP11838085A JP11838085A JPH0482138B2 JP H0482138 B2 JPH0482138 B2 JP H0482138B2 JP 11838085 A JP11838085 A JP 11838085A JP 11838085 A JP11838085 A JP 11838085A JP H0482138 B2 JPH0482138 B2 JP H0482138B2
- Authority
- JP
- Japan
- Prior art keywords
- formula
- fluoro
- chloro
- nitroaniline
- general formula
- 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
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は、医薬品の中間体として有用な一般式
（式中、Ｙは水素または塩素を示す）
で表わされるハロゲノニトロアニリン誘導体およ
びその製造方法に関する。[Detailed Description of the Invention] [Industrial Application Field] The present invention provides a general formula useful as an intermediate for pharmaceuticals. (In the formula, Y represents hydrogen or chlorine.) The present invention relates to a halogenonitroaniline derivative represented by the formula (wherein, Y represents hydrogen or chlorine) and a method for producing the same.
本発明化合物は、本発明者らによつて初めて合
成された新規化合物であつて、本発明者らによつ
て開発された極めて有用な新規抗菌剤８−クロロ
−１−シクロプロピル−６−フルオロ−１，４−
ジヒドロ−７−（４あるいは３−メチル−１−ピ
ペラジニルまたは無置換１−ピペラジニル）−４
−オキソ−３−キノリンカルボン酸等の製造中間
体として使用される。
The compound of the present invention is a novel compound synthesized for the first time by the present inventors, and is an extremely useful new antibacterial agent 8-chloro-1-cyclopropyl-6-fluoro, which was developed by the present inventors. -1,4-
Dihydro-7-(4 or 3-methyl-1-piperazinyl or unsubstituted 1-piperazinyl)-4
-Used as an intermediate in the production of oxo-3-quinolinecarboxylic acid, etc.
かかる一般式（）で表わされる化合物は以下
に記載の如く製造される。
The compound represented by the general formula () is produced as described below.
すなわち、一般式
（式中、Ｒは低級アルキル基を示す）
で表わされる化合物を濃硫酸中で−20℃から100
℃、好ましくは０℃から室温で硝酸あるいはその
塩例えば硝酸カリ、硝酸ナトリウム等と反応させ
る事により一般式
（式中、Ｒは前記に同じ）
で表わされるニトロ化合物が製造される。次にこ
の化合物〔′〕を一般に良く知られた加水分解
方法、例えば塩酸、希硫酸あるいはこれらとアル
コールや酢酸の混液中で加温する方法により式
で表わされる３−クロロ−４−フルオロ−６−ニ
トロアニリンに誘導する。 That is, the general formula (In the formula, R represents a lower alkyl group) The compound represented by
By reacting with nitric acid or its salts such as potassium nitrate, sodium nitrate, etc. at temperatures ranging from 0°C to room temperature, the general formula A nitro compound represented by (wherein R is the same as above) is produced. Next, this compound ['] is subjected to a generally well-known hydrolysis method, such as a method of heating in hydrochloric acid, dilute sulfuric acid, or a mixture of these and alcohol or acetic acid to obtain the formula 3-chloro-4-fluoro-6-nitroaniline represented by
更に化合物〔〕は適当な溶媒、例えば酢酸中
で０℃から100℃、好ましくは10℃から50℃にて
適当なクロル化剤を作用させ塩素を導入する事に
より式
で表わされる２，３−ジクロロ−４−フルオロ−
６−ニトロアリニンに変換される。 Furthermore, the compound [] can be converted to the formula by introducing chlorine through the action of a suitable chlorinating agent at 0°C to 100°C, preferably 10°C to 50°C, in a suitable solvent such as acetic acid. 2,3-dichloro-4-fluoro-
Converted to 6-nitroalinine.
以下、実施例により本発明を説明する。 The present invention will be explained below with reference to Examples.
実施例 １
Ｎ−（３−クロロ−４−フルオロフエニル）ア
セタミドの合成
３−クロロ−４−フルオロアニリン100ｇ
（0.687mol）に無水酢酸200mlを加えると発熱が
起こる。30分間放置後、反応液を１の水に注
ぎ、析出物を濾取してエタノール400mlに溶かし、
熱水600mlを加えて時々攪拌しながら放冷し、析
出晶を濾取して目的物119.4ｇを得た。融点118〜
119℃
元素分析値（％）：C8H7ClFNO
計算値 Ｃ：51.22，Ｈ：3.76，Ｎ：7.47
実測値 Ｃ：51.04，Ｈ：3.72，Ｎ：7.43
実施例 ２
Ｎ−（３−クロロ−４−フルオロ−６−ニトロ
フエニル）アセタミドの合成
Ｎ−（３−クロロ−４−フルオロフエニル）ア
セタミド55ｇ（0.293mol）を濃硫酸165mlに溶か
し、氷−食塩浴中で攪拌しながら、濃硝酸
（d1.42）154mlを５〜10℃、１時間で滴下した。
同温で１時間攪拌後、反応液を氷水中に注ぎ、析
出物を濾取して十分に水洗し、アセトニトリルか
ら再結晶して、黄色針状晶の目的物48.9ｇを得
た。Example 1 Synthesis of N-(3-chloro-4-fluorophenyl)acetamide 100 g of 3-chloro-4-fluoroaniline
When 200ml of acetic anhydride is added to (0.687mol), heat is generated. After standing for 30 minutes, the reaction solution was poured into water from step 1, the precipitate was collected by filtration, and dissolved in 400 ml of ethanol.
600 ml of hot water was added, and the mixture was allowed to cool with occasional stirring, and the precipitated crystals were collected by filtration to obtain 119.4 g of the desired product. Melting point 118~
119℃ Elemental analysis value (%): C 8 H 7 ClFNO Calculated value C: 51.22, H: 3.76, N: 7.47 Actual value C: 51.04, H: 3.72, N: 7.43 Example 2 N-(3-chloro- Synthesis of 4-fluoro-6-nitrophenyl) acetamide 55 g (0.293 mol) of N-(3-chloro-4-fluorophenyl) acetamide was dissolved in 165 ml of concentrated sulfuric acid, and while stirring in an ice-salt bath, concentrated nitric acid ( d1.42) 154 ml was added dropwise at 5 to 10°C over 1 hour.
After stirring at the same temperature for 1 hour, the reaction solution was poured into ice water, and the precipitate was collected by filtration, thoroughly washed with water, and recrystallized from acetonitrile to obtain 48.9 g of the desired product in the form of yellow needles.
融点114〜115℃
元素分析値（％）：C8H6ClFN2O3
計算値 Ｃ：41.31，Ｈ：2.60，Ｎ：12.04
実測値 Ｃ：41.48，Ｈ：2.52，Ｎ：12.13
実施例 ３
３−クロロ−４−フルオロ−６−ニトロアニリ
ンの合成
Ｎ−（３−クロロ−４−フルオロ−６−ニトロ
フエニル）アセタミド30ｇ（0.129mol）を濃塩
酸50ml及びエタノール200mlの混合溶液に加え、
2.5時間還流した。反応液に氷水300mlを加え、析
出晶を濾取、水洗し、乾燥して黄色針状晶の目的
物24.9ｇを得た。融点149.5〜150℃
元素分析値（％）：C8H4ClFN2O2
計算値 Ｃ：37.82，Ｈ：2.11，Ｎ：14.70
実測値 Ｃ：37.85，Ｈ：2.03，Ｎ：14.80
実施例 ４
２，３−ジクロロ−４−フルオロ−６−ニトロ
アニリンの合成
３−クロロ−４−フルオロ−６−ニトロアニリ
ン14.3ｇ（0.075mol）を酢酸150mlに溶かし、18
〜20℃で70分間塩素ガスを吹き込んだ。反応液を
氷水300mlに注ぎ、析出物を濾取して水洗し、エ
タノールから再結晶して黄色針状晶の目的物
14.33ｇを得た。融点161℃
元素分析値（％）：C6H3Cl2FN2O2
計算値 Ｃ：32.03，Ｈ：1.34，Ｎ：12.45
実測値 Ｃ：32.17，Ｈ：1.26，Ｎ：12.65 Melting point 114-115℃ Elemental analysis value (%): C 8 H 6 CLFN 2 O 3 Calculated value C: 41.31, H: 2.60, N: 12.04 Actual value C: 41.48, H: 2.52, N: 12.13 Example 3 3 -Synthesis of chloro-4-fluoro-6-nitroaniline Add 30 g (0.129 mol) of N-(3-chloro-4-fluoro-6-nitrophenyl)acetamide to a mixed solution of 50 ml of concentrated hydrochloric acid and 200 ml of ethanol.
Refluxed for 2.5 hours. 300 ml of ice water was added to the reaction solution, and the precipitated crystals were collected by filtration, washed with water, and dried to obtain 24.9 g of the desired product in the form of yellow needle-like crystals. Melting point 149.5-150℃ Elemental analysis value (%): C 8 H 4 ClFN 2 O 2 Calculated value C: 37.82, H: 2.11, N: 14.70 Actual value C: 37.85, H: 2.03, N: 14.80 Example 4 2 , 3-dichloro-4-fluoro-6-nitroaniline Dissolve 14.3 g (0.075 mol) of 3-chloro-4-fluoro-6-nitroaniline in 150 ml of acetic acid,
Chlorine gas was bubbled for 70 min at ~20°C. The reaction solution was poured into 300 ml of ice water, the precipitate was collected by filtration, washed with water, and recrystallized from ethanol to obtain the desired product as yellow needle-shaped crystals.
14.33g was obtained. Melting point 161℃ Elemental analysis value (%): C 6 H 3 Cl 2 FN 2 O 2 Calculated value C: 32.03, H: 1.34, N: 12.45 Actual value C: 32.17, H: 1.26, N: 12.65
Claims (1)
びその塩。 ２ 一般式 （式中、Ｒは低級アルキル基を示す） で表わされる化合物をニトロ化したのち、加水分
解する事を特徴とする式 で表わされる３−クロロ−４−フルオロ−６−ニ
トロアニリンの製造方法。 ３ ３−クロロ−４−フルオロ−６−ニトロアニ
リンをクロル化剤で処理する事を特徴とする式 で表わされる２，３−ジクロロ−４−フルオロ−
６−ニトロアリニンの製造方法。[Claims] 1. General formula (In the formula, Y represents hydrogen or chlorine.) A halogenonitroaniline derivative and a salt thereof. 2 General formula (In the formula, R represents a lower alkyl group) A formula characterized by nitrating and then hydrolyzing the compound represented by A method for producing 3-chloro-4-fluoro-6-nitroaniline represented by 3 Formula characterized by treating 3-chloro-4-fluoro-6-nitroaniline with a chlorinating agent 2,3-dichloro-4-fluoro-
Method for producing 6-nitroalinine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11838085A JPS61205238A (en) | 1985-05-31 | 1985-05-31 | Halogenonitroaniline derivative and production thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11838085A JPS61205238A (en) | 1985-05-31 | 1985-05-31 | Halogenonitroaniline derivative and production thereof |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP60046216A Division JPS61205258A (en) | 1985-03-08 | 1985-03-08 | Quinolonecarboxylic acid derivative and production thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS61205238A JPS61205238A (en) | 1986-09-11 |
| JPH0482138B2 true JPH0482138B2 (en) | 1992-12-25 |
Family
ID=14735264
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP11838085A Granted JPS61205238A (en) | 1985-05-31 | 1985-05-31 | Halogenonitroaniline derivative and production thereof |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS61205238A (en) |
-
1985
- 1985-05-31 JP JP11838085A patent/JPS61205238A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS61205238A (en) | 1986-09-11 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| LAPS | Cancellation because of no payment of annual fees |