JPH0713041B2 - Halogenonitrobenzene derivative and method for producing the same - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a general formula useful as an intermediate for pharmaceuticals. (Wherein, X represents chlorine or fluorine) and a halogenonitrobenzene derivative represented by the formula and a method for producing the same.

[Problems to be solved by the invention]

The compound of the present invention is a novel compound synthesized for the first time by the present inventors and is a very useful novel antibacterial agent 8-chloro-1-cyclopropyl-6-fluoro-1,4 developed by the present inventors. -Dihydro-7- (4 or 3
-Methyl-1-piperazinyl or unsubstituted 1-piperazinyl) -4-oxo-3-quinolinecarboxylic acid and the like are used as intermediates for the production.

[Means for solving problems]

The compound represented by the general formula [I] is produced as described below.

That is, 2,3-dichloro-4-fluoro-6-nitroaniline [II] is diazotized with nitrite in an aqueous hydrochloric acid solution and boiled in the presence or absence of copper powder, or
The diazo solution is treated with copper chloride at a temperature from 0 ° C. to the boiling point of the solvent, or more preferably in a suitable solvent such as acetonitrile, dimethylformamide or the like, 2,3-dichloro-4-fluoro- Production of 2,3,4-trichloro-5-fluoronitrobenzene [III] by reacting 6-nitroaniline [II] with cupric chloride and nitrite such as tertiary butyl nitrite at room temperature to 100 ° C You can do it.

Further, the compound [III] is heated to 100 to 200 ° C. in at least twice the molar amount of metal fluoride such as potassium fluoride or cesium fluoride and a suitable solvent such as dimethyl sulfoxide, sulfolane or dimethylformamide. As a result, 3-chloro-2,4,5-trifluoronitrobenzene [I
V].

〔Example〕

 Hereinafter, the present invention will be described with reference to examples.

Example 1 Synthesis of N- (3-chloro-4-fluorophenyl) acetamide When 200 g of acetic anhydride is added to 100 g (0.687 mol) of 3-chloro-4-fluorophenyl, an exotherm occurs. After standing for 30 minutes, the reaction solution was poured into 1 water, 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. got g. Melting point
One hundred eighteen to one hundred nineteen ° C. Elemental analysis _{(%): C 8 H 7} ClFNO Calcd C: 51.22, H: 3.76, N: 7.47 Found C: 51.04, H: 3.72, N: 7.43 Example 2 N-(3- Synthesis of chloro-4-fluoro-6-nitrophenyl) acetamide N- (3-chloro-4-fluorophenyl) acetamide
Dissolve 55 g (0.293 mol) in 165 ml concentrated sulfuric acid, and stir in a ice-salt bath while adding 154 ml of concentrated nitric acid (d1.42) at 5 to 10 ° C.
Dropped over time. After stirring at the same temperature for 1 hour, the reaction solution was poured into ice water, the precipitate was collected by filtration, washed thoroughly with water, and recrystallized from acetonitrile to obtain 48.9 g of the objective product as yellow needle crystals.

Mp 114-115 ° C. Elemental analysis _{(%): C 8 H 6} ClFN 2 O 3 Calculated C: 41.31, H: 2.60, N: 12.04 Found C: 41.48, H: 2.52, N: 12.13 Example 3 3 -Chloro-4-fluoro-6-nitroaniline synthesis N- (3-chloro-4-fluoro-6-nitrophenyl) acetamide 30 g (0.129 mol) was added to a mixed solution of concentrated hydrochloric acid 50 ml and ethanol 200 ml for 2.5 hours. Refluxed. Ice water (300 ml) 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 as yellow needle crystals. Mp 149.5-150 ° C. Elemental analysis _{(%): C 6 H 4} ClFN 2 O 2 Calculated C: 37.82, H: 2.11, N: 14.70 Found C: 37.85, H: 2.03, N: 14.80 Example 4 2 Synthesis of 3,3-dichloro-4-fluoro-6-nitroaniline 3-chloro-4-fluoro-6-nitroaniline 14.3 g
(0.075 mol) was dissolved in 150 ml of acetic acid, and chlorine gas was blown thereinto at 18 to 20 ° C for 70 minutes. 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 14.33 g of the desired product as yellow needle crystals. Mp 161 ° C. Elemental analysis _{(%): C 6 H 3} Cl 2 FN 2 O 2 Calculated C: 32.03, H: 1.34, N: 12.45 Found C: 32.17, H: 1.26, N: 12.65 Example 5 2 Synthesis of 3,3,4-trichloro-5-fluoronitrobenzene 13.58 g (0.10 mol) anhydrous cupric chloride and 12.4 g (0.12 mol) tertiary butyl nitrite anhydrous acetonitrile 10
To the 0 ml solution, 18.05 g (0.08 mol) of 2,3-dichloro-4-fluoro-6-nitroaniline was added little by little over 30 minutes at 60 to 62 ° C. After stirring at 60-65 ° C for 30 minutes, cool the reaction mixture to ice-water.
Pour into dilute hydrochloric acid (dilute hydrochloric acid 100 ml, ice water 200 ml) and add benzene 10
Extract 3 times with 0 ml, wash the organic layer successively with dilute hydrochloric acid and water, dry over anhydrous sodium sulfate and concentrate, and distill the residue to obtain the desired product.
Obtained 17.26 g.

Boiling point 137-142 ° C / 27 mmHg NMR (δ in CDCl ₃ ), 7.65 (d, J = 7.5 Hz) Example 6 Synthesis of 3-chloro-2,4,5-trifluoronitrobenzene Anhydrous containing 64.9 g of potassium fluoride Dimethyl sulfoxide 2
To the 30 ml suspension, 54.4 g of 2,3,4-trichloro-5-fluoronitrobenzene was added at 140 ° C, and the mixture was stirred at the same temperature for 10 minutes. The reaction solution was poured into 700 ml of ice water, extracted with petroleum ether, the organic layer was washed successively with water, an aqueous potassium carbonate solution and water, dried over anhydrous sodium sulfate, and concentrated to obtain a residue, which was purified by distillation. 9.7 g of the desired product was obtained.

Boiling point 95-108 ° C / 30mmHg NMR (δ in CDCl ₃ ), 7.94 (ddd, J = 6.7,7.6,9.0Hz)

Claims (3)

[Claims] 1. A general formula (In the formula, X represents chlorine or fluorine) A halogenonitrobenzene derivative represented by the formula: 2. A method of reacting 2,3-dichloro-4-fluoro-6-nitroaniline with nitrous acid or its ester and copper chloride, 2,3,4-trichloro-5-.
Method for producing fluoronitrobenzene. 3. A method comprising reacting 2,3,4-trichloro-5-fluoronitrobenzene with a metal fluoride salt.
Process for producing chloro-2,4,5-trifluoronitrobenzene.