1-(2-Chloro-3-pyridinyl)-1-ethanone
[CAS# 55676-21-6]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyridine compound >> Chloropyridine
• Name: 1-(2-Chloro-3-pyridinyl)-1-ethanone
• Molecular Formula: C₇H₆ClNO
• Molecular Weight: 155.58
• CAS Registry Number: 55676-21-6
• EC Number: 695-379-8
• SMILES: CC(=O)C1=C(N=CC=C1)Cl

Properties

• Density: 1.2±0.1 g/cm³ Calc.^*
• Boiling point: 232.0±20.0 °C 760 mmHg (Calc.)^*
• Flash point: 94.1±21.8 °C (Calc.)^*
• Index of refraction: 1.535 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H335
• Safety Statements: P261-P264-P264+P265-P270-P271-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P319-P321-P330-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin irritation	Skin Irrit.	2	H315
Acute toxicity	Acute Tox.	4	H302
Specific target organ toxicity - single exposure	STOT SE	3	H335
Eye irritation	Eye Irrit.	2	H319
Acute toxicity	Acute Tox.	3	H331
Acute toxicity	Acute Tox.	3	H301
Acute toxicity	Acute Tox.	4	H332
Eye irritation	Eye Irrit.	2A	H319
Acute toxicity	Acute Tox.	3	H311
Acute toxicity	Acute Tox.	4	H312

Discovery and Applications

1-(2-Chloro-3-pyridinyl)-1-ethanone is a chlorinated heteroaromatic ketone consisting of a pyridine ring substituted at the 2-position with a chlorine atom and at the 3-position with an ethanone group. As a halogenated pyridyl ketone, this compound has been utilized primarily as a synthetic intermediate in the development of bioactive molecules, particularly in medicinal and agrochemical research.

The compound belongs to a broader class of substituted pyridines, which are widely recognized for their pharmacological relevance and synthetic versatility. Pyridine rings, due to their nitrogen atom, exhibit electron-deficient aromatic character, making them useful scaffolds for various electrophilic and nucleophilic substitution reactions. The chlorine substituent at the 2-position further modulates the electronic properties of the ring, increasing its reactivity toward nucleophilic aromatic substitution (SNAr), while the carbonyl group at the 3-position provides a reactive site for condensation and addition reactions.

1-(2-Chloro-3-pyridinyl)-1-ethanone is typically synthesized through the acylation of 2-chloro-3-pyridine using acetylating agents such as acetyl chloride or acetic anhydride in the presence of a Lewis acid catalyst. The resulting ketone displays reactivity patterns characteristic of both aryl ketones and halogenated heterocycles, making it suitable for a range of downstream chemical transformations.

One of the principal applications of this compound is in the synthesis of more complex heterocyclic frameworks for pharmaceutical purposes. The carbonyl functionality at the ethanone moiety can undergo transformations such as oxime formation, hydrazone formation, or enamine condensation, enabling the synthesis of various heterocyclic rings that are common in therapeutic agents. In particular, derivatives of this compound have been used in the design of kinase inhibitors and other small-molecule modulators with anti-inflammatory, antiviral, or anticancer activity.

The 2-chloropyridinyl moiety is known for its role in enhancing binding interactions with biological targets due to its electronic properties and ability to participate in hydrogen bonding or halogen bonding. As a result, synthetic chemists often employ this group in lead optimization during drug discovery efforts. By varying the substituents on the ethanone group, researchers can explore structure–activity relationships and optimize properties such as potency, selectivity, and metabolic stability.

In agrochemical chemistry, halogenated pyridines like 1-(2-chloro-3-pyridinyl)-1-ethanone have been incorporated into the design of compounds with herbicidal and insecticidal properties. The chloro-substituted pyridine ring is a known pharmacophore in several commercial crop protection agents. The compound can be further derivatized to generate active ingredients that disrupt enzymatic pathways in target pests or weeds while minimizing toxicity to crops and humans.

The synthetic utility of 1-(2-chloro-3-pyridinyl)-1-ethanone also extends to the preparation of pyridine-based ligands for coordination chemistry. The electron-withdrawing effects of the chlorine and carbonyl groups enhance the coordinating ability of the nitrogen atom in the pyridine ring, allowing for the formation of stable metal-ligand complexes. These complexes are of interest in the development of homogeneous catalysts, sensors, and coordination polymers.

Overall, 1-(2-chloro-3-pyridinyl)-1-ethanone is a valuable intermediate in synthetic organic chemistry. Its dual functionality as a halogenated pyridine and a ketone offers chemists a versatile platform for the generation of structurally diverse and biologically relevant molecules across multiple domains of research and application.

References

1998. Functionalization of pyridines. 2. Synthesis of acylpyridines, pyridinecarboxylic acids, and their derivatives. Review. Chemistry of Heterocyclic Compounds, 34(8).
DOI: 10.1007/bf02311322

2022. Methods for the synthesis of 1H-pyrazolo[3,4-b]pyridine derivatives. Russian Chemical Bulletin, 71(5).
DOI: 10.1007/s11172-022-3487-1

2013. Microwave-assisted synthesis of five-membered S-heterocycles. Journal of the Iranian Chemical Society, 11(2).
DOI: 10.1007/s13738-013-0325-2