Ethyl 4,6-dichloronicotinate
[CAS# 40296-46-6]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyridine compound >> Pyridine derivative
• Name: Ethyl 4,6-dichloronicotinate
• Synonyms: 4,6-Dichloropyridine-3-carboxylic acid ethyl ester
• Molecular Formula: C₈H₇Cl₂NO₂
• Molecular Weight: 220.05
• CAS Registry Number: 40296-46-6
• EC Number: 803-915-0
• SMILES: CCOC(=O)C1=CN=C(C=C1Cl)Cl

Properties

• Density: 1.4±0.1 g/cm³ Calc.^*
• Boiling point: 276.3±35.0 ºC 760 mmHg (Calc.)^*
• Flash point: 120.9±25.9 ºC (Calc.)^*
• Index of refraction: 1.541 (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

Ethyl 4,6-dichloronicotinate is a chemical compound that belongs to the class of nicotinic acid derivatives. It is characterized by the presence of ethyl ester functionality at the carboxyl group of nicotinic acid, with chlorine atoms at the 4 and 6 positions of the pyridine ring. This molecule has garnered attention in various chemical fields, including organic synthesis and pharmaceutical research, due to its unique structure and potential applications.

The discovery of ethyl 4,6-dichloronicotinate is tied to the exploration of halogenated pyridine derivatives, which are commonly synthesized for their bioactive properties. Halogenation, especially with chlorine, is a widely used strategy in medicinal chemistry and materials science, as halogen atoms can influence both the electronic properties and reactivity of organic compounds. The introduction of the ethyl ester group further increases the compound's solubility and accessibility in organic reactions, making it useful as an intermediate in the synthesis of more complex molecules.

The synthesis of ethyl 4,6-dichloronicotinate typically involves the halogenation of nicotinic acid derivatives using chlorine or other chlorinating agents, followed by esterification of the resulting acid with ethanol or ethyl alcohol. The selective introduction of chlorine atoms at the 4 and 6 positions of the pyridine ring can be controlled by carefully selecting reaction conditions and reagents, ensuring high yields and purity of the final product. This compound can also be synthesized through direct chlorination methods or via coupling reactions with appropriate electrophiles.

Ethyl 4,6-dichloronicotinate has a variety of applications, particularly in medicinal chemistry. It serves as an important intermediate in the synthesis of pharmaceutical compounds, including those aimed at treating a range of diseases. The halogenation of pyridine derivatives, like ethyl 4,6-dichloronicotinate, is commonly employed in the preparation of compounds with anticancer, anti-inflammatory, and antimicrobial properties. The dichloro substitution pattern in the pyridine ring can increase the compound's stability and enhance its interaction with biological targets, making it useful in drug discovery efforts.

This compound is also used as a building block in the development of agrochemicals. Its derivatives have been explored for their potential as herbicides and pesticides, where the chlorine substitution pattern enhances the bioactivity and selectivity toward target organisms. The ability of ethyl 4,6-dichloronicotinate to undergo further chemical transformations, such as nucleophilic substitution reactions, makes it a versatile precursor for a wide range of functionalized products.

In materials science, ethyl 4,6-dichloronicotinate can serve as a precursor to other functionalized nicotinic acid derivatives used in the synthesis of organic semiconductors and other advanced materials. The chlorinated pyridine ring is of interest for designing materials with specific electronic and optical properties, which can be applied in the development of electronic devices, sensors, and coatings.

In summary, ethyl 4,6-dichloronicotinate is a significant compound in organic chemistry and pharmaceutical research due to its halogenated pyridine structure. Its synthesis involves the chlorination of nicotinic acid derivatives followed by esterification, and it is widely used as an intermediate in the production of pharmaceuticals, agrochemicals, and materials. Its ability to undergo further chemical transformations, along with its bioactivity, makes it a valuable compound in various chemical industries.

References

2024. An improved synthetic strategy for the multigram-scale synthesis of DNA-PK inhibitor AZD7648. Chemical Papers, 78(7).
DOI: 10.1007/s11696-024-03306-8

2022. Synthesis of an Adaptor-Associated Kinase 1 Inhibitor. Synfacts, 18(5).
DOI: 10.1055/s-0041-1738033