3,4,5,6-Tetrachloropyridine-2-carbonitrile
[CAS# 17824-83-8]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyridine compound >> Chloropyridine
• Name: 3,4,5,6-Tetrachloropyridine-2-carbonitrile
• Molecular Formula: C₆Cl₄N₂
• Molecular Weight: 241.89
• CAS Registry Number: 17824-83-8
• EC Number: 241-784-6
• SMILES: C(#N)C1=C(C(=C(C(=N1)Cl)Cl)Cl)Cl

Properties

• Density: 1.8±0.1 g/cm³ Calc.^*
• Boiling point: 297.4±35.0 ºC 760 mmHg (Calc.)^*
• Flash point: 133.6±25.9 ºC (Calc.)^*
• Index of refraction: 1.621 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS06;GHS07;GHS09 Danger
• Hazard Statements: H301-H302-H315-H317-H319-H335-H400-H410
• Precautionary Statements: P261-P264-P264+P265-P270-P271-P272-P273-P280-P301+P316-P301+P317-P302+P352-P304+P340-P305+P351+P338-P319-P321-P330-P332+P317-P333+P317-P337+P317-P362+P364-P391-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
Acute toxicity	Acute Tox.	3	H301
Skin sensitization	Skin Sens.	1	H317
Acute hazardous to the aquatic environment	Aquatic Acute	1	H400
Acute toxicity	Acute Tox.	4	H302
Chronic hazardous to the aquatic environment	Aquatic Chronic	1	H410

Discovory and Applicatios

3,4,5,6-Tetrachloropyridine-2-carbonitrile is a halogenated pyridine derivative characterized by the presence of four chlorine atoms on the pyridine ring at the 3, 4, 5, and 6 positions and a nitrile group at the 2 position. This compound belongs to a broader class of chloropyridines that have been extensively studied for their chemical reactivity and potential applications in the synthesis of complex molecules.

The discovery of 3,4,5,6-tetrachloropyridine-2-carbonitrile traces back to investigations in the mid-20th century focused on the functionalization of pyridine rings. Chlorination of pyridine derivatives under controlled conditions was a common strategy to increase chemical stability and modulate electronic properties. Specifically, the synthesis of this compound typically involves chlorination of 2-cyanopyridine using strong chlorinating agents such as phosphorus pentachloride (PCl₅) or thionyl chloride (SOCl₂) in the presence of catalysts or under thermal activation. Alternatively, tetrachloropyridine precursors can undergo cyanation reactions to introduce the nitrile group selectively at the 2 position.

In terms of chemical behavior, the multiple chlorine substituents on the aromatic ring exert a strong electron-withdrawing effect, significantly affecting the reactivity of the pyridine core. The presence of these substituents decreases the nucleophilicity of the nitrogen atom in the ring and makes the carbon atoms of the ring more electrophilic. As a result, 3,4,5,6-tetrachloropyridine-2-carbonitrile is particularly useful as an intermediate in nucleophilic aromatic substitution (S_NAr) reactions, where one or more chlorine atoms can be selectively displaced by nucleophiles such as amines, alkoxides, or thiolates under mild conditions.

Applications of 3,4,5,6-tetrachloropyridine-2-carbonitrile are mainly found in the synthesis of advanced agrochemicals, pharmaceuticals, and specialty materials. Its use in agrochemical research includes the construction of herbicides and fungicides where the pyridine ring acts as a central scaffold for biological activity. The electron-deficient nature of the ring facilitates the attachment of various functional groups that can enhance the selectivity and potency of bioactive molecules. In pharmaceutical development, derivatives of chloropyridines have been explored for their antimicrobial, antiviral, and anticancer properties, although 3,4,5,6-tetrachloropyridine-2-carbonitrile itself is more commonly employed as a synthetic building block rather than an active pharmaceutical ingredient.

In materials science, compounds derived from 3,4,5,6-tetrachloropyridine-2-carbonitrile have been investigated for their electronic and optical properties. The introduction of donor or acceptor groups through nucleophilic substitution can generate molecules with tailored charge-transport characteristics, making them candidates for applications in organic electronics, such as organic light-emitting diodes (OLEDs) and organic field-effect transistors (OFETs).

The high chemical stability imparted by the multiple chlorine atoms also makes this compound an attractive intermediate for the synthesis of molecules that must endure harsh chemical or environmental conditions. For example, incorporation of chlorinated pyridine units can enhance the durability and resistance of polymers and coatings to oxidative degradation and UV exposure.

Handling of 3,4,5,6-tetrachloropyridine-2-carbonitrile requires appropriate safety measures due to the potential toxicity associated with chlorinated aromatic compounds. Proper personal protective equipment and ventilation are necessary to avoid inhalation or skin contact, and waste disposal must comply with regulations concerning halogenated organic materials.

Overall, 3,4,5,6-tetrachloropyridine-2-carbonitrile is a valuable and well-established compound in synthetic organic chemistry, providing a versatile platform for the development of functionalized molecules across several fields of research and industry.

References

1993. Reactions of polyhalopyridines. 1. Reaction of the isomeric tetrachlorocyanopyridines and pentachloropyridine with salts of N,N-dialkyldithiocarbamic acid and the X-ray structural investigation of the reaction products. Chemistry of Heterocyclic Compounds, 29(9).
DOI: 10.1007/bf00534387

1998. Reactions of polyhalogenopyridines. 15. Reaction of isomeric tetrachlorocyanopyridines and pentachloropyridine with potassium isopropyltrithiocarbonate. Chemistry of Heterocyclic Compounds, 34(3).
DOI: 10.1007/bf02290720

2017. Synthesis, structure, and the energetic properties of tetraazidopyridine-4-carbonitrile. Chemistry of Heterocyclic Compounds, 53(6).
DOI: 10.1007/s10593-017-2124-7