3,5-Dichlorobenzonitrile
[CAS# 6575-00-4]

Identification

• Classification: Chemical reagent >> Organic reagent >> Cyanide/nitrile
• Name: 3,5-Dichlorobenzonitrile
• Molecular Formula: C₇H₃Cl₂N
• Molecular Weight: 172.01
• CAS Registry Number: 6575-00-4
• EC Number: 229-495-3
• SMILES: C1=C(C=C(C=C1Cl)Cl)C#N

Properties

• Density: 1.4±0.1 g/cm³ Calc.^*
• Melting point: 64 - 66 ºC (Expl.)
• Boiling point: 223.3±20.0 ºC 760 mmHg (Calc.)^*
• Flash point: 85.8±16.0 ºC (Calc.)^*
• Index of refraction: 1.584 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H302-H312-H315-H319-H332-H335
• Precautionary Statements: P261-P264-P264+P265-P270-P271-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P317-P319-P321-P330-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

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

Discovory and Applicatios

3,5-Dichlorobenzonitrile is an aromatic organic compound with the molecular formula C₇H₃Cl₂NO. It consists of a benzene ring substituted with chlorine atoms at the 3 and 5 positions and a nitrile group at the 1 position. The compound is a white to pale yellow crystalline solid under standard conditions and is primarily valued in the chemical industry for its role as an intermediate in the synthesis of agrochemicals, pharmaceuticals, and specialty chemicals.

The development of 3,5-dichlorobenzonitrile as a useful synthetic building block can be traced back to efforts in the mid-20th century to produce halogenated benzonitrile derivatives for agricultural applications. Among various structural isomers, the 3,5-dichloro variant demonstrated particular utility due to the influence of its electron-withdrawing substituents, which enhance the molecule’s reactivity toward nucleophilic aromatic substitution. This reactivity makes it a versatile starting material for the introduction of diverse functional groups on the aromatic ring.

One of the earliest and most notable applications of 3,5-dichlorobenzonitrile was in the synthesis of herbicides. In this context, it serves as a precursor to active ingredients that inhibit plant growth by disrupting amino acid synthesis. Specifically, its use as a key intermediate in the preparation of dichlobenil, a selective herbicide effective against perennial weeds, established its industrial importance. Dichlobenil is applied mainly in non-crop areas such as pathways, railways, and industrial sites to control unwanted vegetation without affecting desired crops.

Beyond agrochemicals, 3,5-dichlorobenzonitrile is also used in the synthesis of pharmaceutical compounds. Its nitrile group provides a functional handle for subsequent modifications, including conversion to amides, amines, and carboxylic acids. In drug discovery, it has been employed in the preparation of small-molecule libraries, particularly for compounds that target neurological receptors and enzymes. The dichloro substitution pattern is known to modulate lipophilicity and metabolic stability, traits desirable in medicinal chemistry for optimizing the pharmacokinetic profile of lead compounds.

In materials chemistry, derivatives of 3,5-dichlorobenzonitrile are used in the preparation of liquid crystalline compounds and polymers. Its ability to participate in cross-coupling reactions, such as Suzuki or Sonogashira coupling, allows the construction of extended π-conjugated systems, which are critical for the development of optoelectronic materials.

Industrial production of 3,5-dichlorobenzonitrile typically involves chlorination of benzonitrile under controlled conditions, ensuring selective substitution at the desired positions. Alternatively, it can be synthesized via Sandmeyer-type reactions starting from 3,5-dichloroaniline. These processes are designed to minimize by-products and maximize yield while adhering to environmental and safety regulations.

Due to its toxicity and environmental persistence, handling of 3,5-dichlorobenzonitrile requires careful attention to safety protocols. Inhalation or ingestion can be harmful, and prolonged exposure may cause irritation or sensitization. Accordingly, its storage and disposal are subject to regulatory oversight in many countries to prevent environmental contamination.

In summary, 3,5-dichlorobenzonitrile is a well-established intermediate with applications across multiple industries. Its discovery and development reflect a broader trend in synthetic chemistry to utilize halogenated aromatics as modular and reactive compounds. Continued research into its derivatives contributes to innovation in areas ranging from agriculture to pharmaceuticals and advanced materials.

References

2020. Synthesis of Dichlorobenzamide Derivatives: Crystal Structures of 3,5-Dichloro-N-(2-chlorophenyl)benzamide and 3,5-Dichloro-N-(4-chlorophenyl)benzamide. Journal of Chemical Crystallography, 50(4).
DOI: 10.1007/s10870-020-00822-9

2013. FT-IR, FT-Raman spectra and other molecular properties of 3,5-dichlorobenzonitrile: A DFT study. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 116.
DOI: 10.1016/j.saa.2013.07.028

2007. Nucleophilic Attack on Nitriles. Science of Synthesis, 1.
URL: https://science-of-synthesis.thieme.com/app/text/?id=SD-033-00565