5-Chloro-3-methyl-4-nitro-1H-pyrazole: Properties & Applications
5-Chloro-3-methyl-4-nitro-1H-pyrazole: Properties & Applications
5-chloro-3-methyl-4-nitro-1H-pyrazole is a halogenated, nitro-substituted pyrazole heterocycle widely employed as a versatile synthetic building block in medicinal chemistry, agrochemical research, and the preparation of structurally diverse pharmacologically active compounds.
- IUPAC Name
- 5-chloro-3-methyl-4-nitro-1H-pyrazole
- Molecular Formula
- C4H4ClN3O2
- Molecular Weight
- 161.55 g/mol
- Key Functional Groups
- Chloro (C-5), Nitro (C-4), Methyl (C-3), NH (N-1)
- Catalog SKU
- C177168
- Compound Class
- Halogenated nitropyrazole heterocycle
- Primary Application
- Synthetic building block for medicinal and agrochemical research
Chemical Structure and Physicochemical Properties
5-Chloro-3-methyl-4-nitro-1H-pyrazole (CAS catalog SKU: C177168) belongs to the pyrazole family of five-membered nitrogen-containing heterocycles. Its molecular formula is C4H4ClN3O2 with a molecular weight of approximately 161.55 g/mol. The compound features three electronically distinct substituents on the pyrazole ring: a chloro group at the 5-position, a nitro group at the 4-position, and a methyl group at the 3-position, along with a free NH at the 1-position.
The combination of electron-withdrawing nitro and chloro groups with the electron-donating methyl group results in a polarized, aromatic ring system. The NH tautomer is typically favored in solid state. The nitro group at C-4 activates the adjacent C-5 position toward nucleophilic aromatic substitution, while the C-5 chloro group serves as a leaving group in such reactions. This electronic profile makes the compound highly reactive and synthetically tractable for further functionalization.
Synthesis and Role as a Building Block
5-Chloro-3-methyl-4-nitro-1H-pyrazole is most commonly prepared by the chlorination of 3-methyl-4-nitro-1H-pyrazole using chlorinating agents such as phosphorus oxychloride (POCl3) or N-chlorosuccinimide (NCS) under controlled conditions. The regioselectivity of chlorination at C-5 is directed by the combined electronic effects of the methyl and nitro substituents already present on the ring.
As a building block, this compound offers multiple handles for diversification. The C-5 chloro group undergoes nucleophilic aromatic substitution (SNAr) with amines, alkoxides, and thiolates to afford 5-amino-, 5-alkoxy-, or 5-thioether-substituted pyrazoles. The nitro group can be reduced to a primary amine, enabling access to 4-aminopyrazole scaffolds that are prevalent in kinase inhibitor chemotypes. The NH can be alkylated or acylated to introduce N-substituents, providing N-substituted pyrazole libraries relevant to fragment-based drug discovery.
Applications in Medicinal and Agrochemical Research
The pyrazole scaffold is one of the most privileged heterocycles in drug discovery, present in numerous approved pharmaceuticals and clinical candidates. 5-Chloro-3-methyl-4-nitro-1H-pyrazole serves as a key precursor in the synthesis of biologically active pyrazole derivatives. The 4-amino derivatives accessible from this compound have been explored in the design of kinase inhibitors, anti-inflammatory agents, and antimicrobial compounds.
In agrochemical research, nitropyrazole-based intermediates have been employed in the synthesis of insecticides and herbicides. The structural flexibility afforded by the three functional handles (Cl, NO2, NH) allows chemists to rapidly explore structure-activity relationships (SAR) by parallel or combinatorial synthesis approaches. This compound is therefore valuable both in early-stage lead identification and in optimization campaigns.
Handling, Storage, and Safety Considerations
5-Chloro-3-methyl-4-nitro-1H-pyrazole should be handled with standard laboratory precautions appropriate for nitroaromatic and organochlorine compounds. Personal protective equipment (PPE) including chemical-resistant gloves, safety goggles, and a laboratory coat should be worn at all times. Operations involving significant quantities should be conducted in a well-ventilated fume hood to minimize inhalation exposure to dust or vapors.
The compound should be stored in a cool, dry place, away from heat sources, open flames, and strong reducing agents. Containers should be kept tightly sealed when not in use to prevent moisture uptake and contamination. Disposal must comply with applicable local, national, and institutional regulations for halogenated and nitro-containing organic waste. Researchers should consult the Safety Data Sheet (SDS) provided with the product (SKU: C177168) for complete hazard information, first-aid measures, and regulatory classifications before use.
Frequently asked questions
What is 5-chloro-3-methyl-4-nitro-1H-pyrazole used for in research?
It is primarily used as a synthetic building block in medicinal chemistry and agrochemical research. The compound's three reactive functional groups—the C-5 chloro, C-4 nitro, and N-1 hydrogen—enable diverse chemical transformations, including nucleophilic aromatic substitution, nitro reduction, and N-alkylation, facilitating rapid access to diverse pyrazole-based compound libraries.
How should 5-chloro-3-methyl-4-nitro-1H-pyrazole (C177168) be stored?
The compound should be stored in a cool, dry, well-ventilated area in a tightly sealed container, away from heat, flames, and incompatible materials such as strong reducing agents. Always refer to the product SDS for specific temperature and humidity storage requirements.
Can the chloro group in 5-chloro-3-methyl-4-nitro-1H-pyrazole be displaced by nucleophiles?
Yes. The electron-withdrawing nitro group at C-4 activates the C-5 position toward nucleophilic aromatic substitution (SᵊAr). Amines, alkoxides, and thiolates are among the nucleophiles that can effectively displace the chloro leaving group under appropriate reaction conditions, providing direct access to 5-substituted pyrazole derivatives.
What is the molecular weight of 5-chloro-3-methyl-4-nitro-1H-pyrazole?
The molecular weight of 5-chloro-3-methyl-4-nitro-1H-pyrazole is approximately 161.55 g/mol, corresponding to the molecular formula C4H4ClN3O2.
Is 5-chloro-3-methyl-4-nitro-1H-pyrazole relevant to kinase inhibitor development?
Yes. Reduction of the nitro group at C-4 yields a 4-aminopyrazole, a scaffold commonly found in kinase inhibitor pharmacophores. This transformation makes 5-chloro-3-methyl-4-nitro-1H-pyrazole a useful precursor for preparing kinase inhibitor candidates in drug discovery programs.
References
- Elguero, J. Pyrazoles. In Comprehensive Heterocyclic Chemistry II; Katritzky, A. R., Rees, C. W., Scriven, E. F. V., Eds.; Pergamon: Oxford, 1996; Vol. 3, pp 1–75.
- Fustero, S.; Sánchez-Roselló, M.; Barrio, P.; Simón-Fuentes, A. From 2000 to Mid-2010: A Fruitful Decade for the Synthesis of Pyrazoles. Chem. Rev. 2011, 111, 6984–7034. doi:10.1021/cr2000459
- Vijesh, A. M.; Isloor, A. M.; Telkar, S.; Arulmoli, T.; Fun, H.-K. Synthesis and antimicrobial studies of some new pyrazole derivatives. Arab. J. Chem. 2013, 6, 197–204. doi:10.1016/j.arabjc.2010.10.009
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