4,6-Dichloronicotinic acid
[CAS# 73027-79-9]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyridine compound >> Pyridine derivative
• Name: 4,6-Dichloronicotinic acid
• Synonyms: 4,6-Dichloropyridine-3-carboxylic acid; 2,4-Dichloro-5-pyridinecarboxylic acid
• Molecular Formula: C₆H₃Cl₂NO₂
• Molecular Weight: 192.00
• CAS Registry Number: 73027-79-9
• EC Number: 695-891-1
• SMILES: C1=C(C(=CN=C1Cl)C(=O)O)Cl

Properties

• Density: 1.6±0.1 g/cm³, Calc.^*
• Index of Refraction: 1.606, Calc.^*
• Boiling Point: 337.0±37.0 ºC (760 mmHg), Calc.^*
• Flash Point: 157.6±26.5 ºC, Calc.^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H315-H319-H335
• Precautionary Statements: P261-P264-P264+P265-P271-P280-P302+P352-P304+P340-P305+P351+P338-P319-P321-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335
Eye irritation	Eye Irrit.	2	H319
Eye irritation	Eye Irrit.	2A	H319

Discovory and Applicatios

4,6-Dichloronicotinic acid is a halogenated derivative of nicotinic acid (also known as niacin), a key compound in the vitamin B3 group. This organic compound features chlorine atoms at the 4 and 6 positions on the aromatic ring of the nicotinic acid structure, alongside the carboxyl group at the 1-position. The substitution of chlorine atoms introduces specific chemical and physical properties, such as increased lipophilicity and reactivity, that make 4,6-dichloronicotinic acid valuable in various applications across chemistry, pharmaceuticals, and material sciences.

The discovery of 4,6-dichloronicotinic acid is rooted in the study of halogenated derivatives of nicotinic acid. These compounds are of significant interest because of their potential biological activity and utility in synthetic chemistry. The synthesis of 4,6-dichloronicotinic acid generally involves the selective chlorination of nicotinic acid under controlled conditions. Chlorine can be introduced to the aromatic ring using reagents such as chlorine gas or thionyl chloride, often in the presence of a solvent and at elevated temperatures to ensure the selective substitution at the desired positions. The availability of 4,6-dichloronicotinic acid as a stable compound allows it to be used as an intermediate in the synthesis of a variety of other chemical entities.

One of the primary applications of 4,6-dichloronicotinic acid is in organic synthesis. The presence of two chlorine atoms on the aromatic ring makes it a versatile starting material for further chemical modifications. These chlorines can be replaced in nucleophilic substitution reactions, enabling the introduction of various functional groups to the aromatic core. This feature is particularly useful in the synthesis of biologically active compounds and materials. The compound's ability to undergo reactions such as cross-coupling, nucleophilic aromatic substitution, and electrophilic aromatic substitution further enhances its role as a building block in synthetic chemistry.

In the field of medicinal chemistry, 4,6-dichloronicotinic acid and its derivatives are explored for their potential pharmacological activities. The structure of nicotinic acid and its derivatives is known to influence key metabolic and receptor pathways, and halogenation at the 4 and 6 positions can modulate these effects. 4,6-Dichloronicotinic acid has shown promise as a scaffold for the development of compounds targeting various diseases, including cancer, inflammation, and neurodegenerative disorders. Halogenated nicotinic acid derivatives have also been studied for their antibacterial and antiviral properties, with several showing potential as lead compounds in drug development. The dichlorination of the nicotinic acid molecule could also enhance its interaction with enzymes or receptors, leading to new therapeutic possibilities.

In agrochemicals, 4,6-dichloronicotinic acid has been studied for its potential as a precursor to the synthesis of pesticides and herbicides. The chlorinated nicotinic acid derivatives are known to interact with nicotinic receptors in pests, disrupting their nervous system and leading to their death. This property makes 4,6-dichloronicotinic acid a candidate for the development of novel, environmentally friendly agrochemicals. The compound’s high reactivity and the ease with which it can be further functionalized offer opportunities to develop selective pest control agents that target specific species without harming non-target organisms.

In material science, 4,6-dichloronicotinic acid is explored for its potential in the design of advanced materials, including polymers, sensors, and optoelectronic devices. The halogenated structure of the compound can affect the electronic properties of materials, making it useful in the development of conductive polymers or materials for energy storage. Moreover, the compound's ability to form coordination complexes with metals may make it a valuable precursor for the synthesis of metal-organic frameworks (MOFs) or catalysts for chemical reactions.

In conclusion, 4,6-dichloronicotinic acid is a highly versatile compound with applications across several fields, including organic synthesis, medicinal chemistry, agrochemicals, and materials science. Its halogenated structure offers unique reactivity and biological properties that are being explored in the development of new drugs, pest control agents, and functional materials. As research continues, the compound's potential in both industrial and pharmaceutical applications is expected to expand further, providing new avenues for the development of advanced chemical products.

References

2008. Methyl 4,6-dichloro-pyridine-3-carboxylate. Acta Crystallographica Section E Structure Reports Online, 64(6).
DOI: 10.1107/s1600536808011914

2007. Via Organolithium Reagents. Science of Synthesis, 31.
URL: https://www.thieme.de/en/thieme-chemistry/science-of-synthesis-54711.htm