3-Chloro-5-nitro-2-(2H-1,2,3-triazol-2-yl)pyridine
[CAS# 1832583-40-0]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyridine compound >> Nitropyridine
• Name: 3-Chloro-5-nitro-2-(2H-1,2,3-triazol-2-yl)pyridine
• Molecular Formula: C₇H₄ClN₅O₂
• Molecular Weight: 225.59
• CAS Registry Number: 1832583-40-0
• SMILES: C1=NN(N=C1)C2=C(C=C(C=N2)[N+](=O)[O-])Cl

Properties

• Density: 1.8±0.1 g/cm³ Calc.^*
• Boiling point: 408.4±55.0 ºC 760 mmHg (Calc.)^*
• Flash point: 200.8±31.5 ºC (Calc.)^*
• Index of refraction: 1.769 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H315-H319-H335
• Precautionary Statements: P261-P305+P351+P338

Discovory and Applicatios

The chemical substance 3-chloro-5-nitro-2-(2H-1,2,3-triazol-2-yl)pyridine is a functionalized pyridine derivative bearing chloro, nitro, and triazole substituents, recognized in organic chemistry as a versatile synthetic intermediate, particularly in pharmaceutical and agrochemical synthesis. Its discovery and applications are well-documented in the literature, rooted in the development of heterocyclic chemistry and triazole functionalization.

The origins of this compound are tied to the study of pyridine derivatives, which have been explored since the 19th century for their presence in natural products and utility as synthetic scaffolds. The introduction of nitro and chloro groups to pyridine rings gained prominence in the mid-20th century, driven by their electron-withdrawing properties and reactivity in nucleophilic substitution. The 1,2,3-triazole moiety, particularly the 2H-isomer, became significant in the late 20th century following advances in click chemistry and triazole synthesis, notably through copper-catalyzed azide-alkyne cycloaddition. The specific combination of a 3-chloro, 5-nitro, and 2-(2H-1,2,3-triazol-2-yl) substitution pattern emerged to meet the pharmaceutical industry’s demand for electron-deficient, heterocyclic intermediates with biologically relevant motifs. Advances in regioselective functionalization during the 1970s and 1980s enabled the precise synthesis of such compounds.

Synthetically, 3-chloro-5-nitro-2-(2H-1,2,3-triazol-2-yl)pyridine is typically prepared through a multi-step process. A common route starts with 2,3-dichloro-5-nitropyridine, where the nitro and chloro groups are pre-installed or introduced via nitration and chlorination of a pyridine precursor. The 2-position is functionalized with the 2H-1,2,3-triazole by nucleophilic aromatic substitution, reacting the 2-chloro group with 1,2,3-triazole under basic conditions to favor N-2 attachment. Alternatively, the triazole can be introduced via a cross-coupling approach, such as a copper-catalyzed reaction of a 2-halo-5-nitropyridine with a triazole precursor. The 3-chloro group is retained or introduced via selective chlorination, ensuring regioselectivity. These steps rely on well-established heterocyclic, nitration, and triazole chemistry protocols, delivering high yields and purity.

The primary application of this compound is as a synthetic intermediate in pharmaceutical chemistry. The pyridine core is a privileged scaffold in drugs targeting cancer, inflammation, and infectious diseases, due to its ability to engage in hydrogen bonding and π-interactions. The 3-chloro group serves as a handle for cross-coupling reactions, such as Suzuki-Miyaura or Buchwald-Hartwig couplings, enabling the introduction of diverse substituents. The 5-nitro group enhances electron deficiency, aiding nucleophilic substitutions, and can be reduced to an amine for further functionalization. The 2H-1,2,3-triazole moiety, known for its stability and bioisosteric properties, improves binding affinity and pharmacokinetic profiles. This compound is frequently used in the synthesis of kinase inhibitors, antimicrobial agents, and receptor modulators, where the combination of electron-withdrawing and heterocyclic groups optimizes target specificity.

In agrochemical synthesis, the compound is employed to develop pesticides and fungicides, where nitro and triazole groups contribute to bioactivity and stability. In academic research, it serves as a model for studying regioselective functionalization, triazole chemistry, and the electronic effects of nitro and chloro substituents. Its synthesis has advanced the development of triazole incorporation and halogenation techniques.

The significance of 3-chloro-5-nitro-2-(2H-1,2,3-triazol-2-yl)pyridine lies in its role as a multifunctional intermediate that combines the biological relevance of pyridine and triazole with the synthetic versatility of chloro and nitro groups. Its development reflects progress in regioselective heterocyclic synthesis and click chemistry. By enabling the efficient synthesis of complex, biologically active molecules, it has become a critical tool in advancing pharmaceutical, agrochemical, and chemical research.