320-98-9 | 5-Fluoro-2-nitrobenzoic acid

CAS:320-98-9 | 5-Fluoro-2-nitrobenzoic acid,Description

Synthesis Analysis

The synthesis of related fluorinated nitrobenzoic acid derivatives is described in several papers. For instance, 4-Chloro-2-fluoro-5-nitrobenzoic acid is synthesized and used as a multireactive building block for the preparation of various heterocyclic compounds, including benzimidazoles and benzotriazoles, which are significant in drug discovery. Another synthesis process for 5-fluoro-2-nitrobenzotrifluoride is achieved using a continuous-flow millireactor system, which offers better control over impurities and higher process efficiency compared to traditional batch reactors. Additionally, a novel route for the synthesis of 5-nitrobenzoxazole derivatives starting from 2-fluoro-5-nitroaniline is reported, highlighting the use of solvent-free conditions and the efficiency of the process.

Molecular Structure Analysis

The molecular structure of related compounds is confirmed through various analytical techniques. Single-crystal X-ray diffraction is used to unambiguously confirm the structure of a series of fluorinated benzimidazole-substituted nitronyl nitroxides. Similarly, the structure of 1-Fluoro-2,5-dimethoxy-4-nitrobenzene is confirmed by X-ray crystallography, along with NMR, elemental analysis, EI-MS, and FT-IR.

Chemical Reactions Analysis

The chemical reactivity of fluorinated nitrobenzoic acid derivatives is explored in the context of their use as intermediates in various reactions. For example, the reaction of 5-fluorobenzimidazolyl-2-thione with chloroacetic acid leads to the synthesis of thiazolo[3,2-a]benzimidazol-3(2-H)-ones, with studies on the orientation of cyclization. The reactivity of these compounds is influenced by their functional groups, which can participate in a variety of chemical transformations.

Physical and Chemical Properties Analysis

The physical and chemical properties of fluorinated nitrobenzoic acid derivatives are characterized in several studies. The acidity and redox properties of a series of fluorinated benzimidazole-substituted nitronyl nitroxides are investigated, revealing that the introduction of fluorine atoms significantly enhances the acidity of the compounds. The supramolecular hydrogen-bonding patterns of 5-fluorouracil cocrystals are studied, demonstrating the importance of specific hydrogen-bond donor and acceptor groups in the design of pharmaceutical cocrystals. Additionally, the use of 7-fluoro-4-nitrobenzo-2-oxa-1,3-diazole as a fluorescent labeling reagent for amino acids in high-performance liquid chromatography is reported, indicating its utility in sensitive detection methods.

Scientific Research Applications

1. Synthesis of 5-fluoro-2-nitrobenzotrifluoride

• Application Summary : 5-fluoro-2-nitrobenzotrifluoride is synthesized in a continuous-flow millireactor system through the nitration of 3-fluorobenzotrifluoride using mixed acid as a nitrating agent.
• Methods of Application : The process safety was evaluated based on the temperature rise with the use of Reaction Calorimeter and Differential Scanning Calorimetry. The mass transfer limitation for this nitration process in the millireactor was evaluated.
• Results or Outcomes : Compared with the traditional batch reactor, the flow reactor could achieve better control over impurity and higher process efficiency because of its enhanced mass and heat transfer rates under the optimized conditions.

2. Synthesis of Active Pharmaceutical Ingredients (APIs)

• Application Summary : 5-fluoro-2-nitrobenzotrifluoride is widely used as an intermediate in the synthesis and development of new active pharmaceutical ingredients (APIs). In particular, it is an important intermediate for synthesis of vasokinetic kinin antagonist, which is used to treat acute pain, neuropathic pain, and inflammatory pain symptoms.
• Methods of Application : An original synthetic process for this intermediate involves the nitration of 3-fluorobenzotrifluoride in batch reactors.
• Results or Outcomes : The synthesis of APIs using 5-fluoro-2-nitrobenzotrifluoride has led to the rapid development of popular antibacterial, anti-inflammatory, and analgesic drugs.

3. Synthesis of p38α Mitogen-Activated Protein Kinase (MAPK) Inhibitors

• Application Summary : 5-Fluoro-2-nitrobenzoic acid participates in the synthesis of novel quinazolinones that are potential inhibitors of p38α mitogen-activated protein kinase (MAPK).
• Methods of Application : The specific methods of application or experimental procedures were not detailed in the source.
• Results or Outcomes : The synthesis of p38α MAPK inhibitors using 5-Fluoro-2-nitrobenzoic acid could potentially lead to the development of new therapeutic agents.

4. Synthesis of Dibenz[b,f]oxazepin-11(10H)-ones

• Application Summary : 2-Fluoro-5-nitrobenzoic acid may be used in the synthesis of dibenz[b,f]oxazepin-11(10H)-ones.
• Methods of Application : The synthesis involves the nucleophilic aromatic substitution (SNAr) of fluorine in 2-fluoro-5-nitrobenzoic acid with the OH of various 2-aminophenols on solid support.
• Results or Outcomes : The specific results or outcomes were not detailed in the source.

5. Synthesis of Substituted Dibenzazocines

• Application Summary : 2-Fluoro-5-nitrobenzoic acid may be used in the synthesis of substituted dibenzazocines.
• Methods of Application : The synthesis involves SNAr of fluorine in 2-fluoro-5-nitrobenzoic acid with the OH function of the immobilized polysubstituted phenols.
• Results or Outcomes : The specific results or outcomes were not detailed in the source.

6. Synthesis of Oxazepines

• Application Summary : 2-Fluoro-5-nitrobenzoic acid may be used in the synthesis of oxazepines.
• Methods of Application : The specific methods of application or experimental procedures were not detailed in the source.
• Results or Outcomes : The specific results or outcomes were not detailed in the source.

7. Synthesis of N1-(2,4-dichlorophenyl)-2-amino-5-fluorobenzamide

• Application Summary : 5-Fluoro-2-nitrobenzoic acid is an intermediate formed during the synthesis of N1-(2,4-dichlorophenyl)-2-amino-5-fluorobenzamide.
• Methods of Application : The specific methods of application or experimental procedures were not detailed in the source.
• Results or Outcomes : The specific results or outcomes were not detailed in the source.

8. Synthesis of Dibenz[b,f]oxazepin-11(10H)-ones 

• Application Summary : 2-Fluoro-5-nitrobenzoic acid may be used in the synthesis of dibenz[b,f]oxazepin-11(10H)-ones.
• Methods of Application : The synthesis involves the nucleophilic aromatic substitution (SNAr) of fluorine in 2-fluoro-5-nitrobenzoic acid with the OH of various 2-aminophenols on solid support.
• Results or Outcomes : The specific results or outcomes were not detailed in the source.

9. Synthesis of Substituted Dibenzazocines

• Application Summary : 2-Fluoro-5-nitrobenzoic acid may be used in the synthesis of substituted dibenzazocines.
• Methods of Application : The synthesis involves SNAr of fluorine in 2-fluoro-5-nitrobenzoic acid with the OH function of the immobilized polysubstituted phenols.
• Results or Outcomes : The specific results or outcomes were not detailed in the source.

Safety And Hazards

5-Fluoro-2-nitrobenzoic acid is considered hazardous. It causes skin irritation, serious eye irritation, and may cause respiratory irritation. It is recommended to wear personal protective equipment/face protection, ensure adequate ventilation, avoid getting it in eyes, on skin, or on clothing, avoid ingestion and inhalation, and avoid dust formation.

Future Directions

5-Fluoro-2-nitrobenzoic acid is widely used as an intermediate in the synthesis and development of new active pharmaceutical ingredients (APIs). It is an important intermediate for the synthesis of vasokinetic kinin antagonist, which is used to treat acute pain, neuropathic pain, and inflammatory pain symptoms. This continuous-flow synthesis strategy would be beneficial for the commercial manufacturing of fine chemicals and pharmaceutical intermediates with the involvement of nitration.

More Information