In the realm of heterocyclic chemistry, 2,4-Dichloropyrimidine (CAS No. 3934-20-1) plays a crucial role as a versatile building block for pharmaceuticals, agrochemicals, and specialty organic compounds. Its ability to undergo selective substitution reactions makes it an indispensable intermediate in the synthesis of biologically active molecules.
This article provides a comprehensive overview of 2,4-Dichloropyrimidine, covering its structure, synthesis routes, physical properties, and major applications across industries.
2,4-Dichloropyrimidine is a chlorinated heterocyclic compound derived from pyrimidine, a six-membered aromatic ring containing two nitrogen atoms. Substitution of chlorine atoms at the 2nd and 4th positions enhances its electrophilic reactivity, making it an excellent precursor for further functionalization.
Chemical Name: 2,4-Dichloropyrimidine
CAS Number: 3934-20-1
Molecular Formula: C₄H₂Cl₂N₂
Molecular Weight: 165.98 g/mol
Appearance: Colorless to light yellow crystalline solid
Structure:
Pyrimidine ring with chlorine atoms at positions 2 and 4
Formula representation:
The pyrimidine ring in 2,4-dichloropyrimidine consists of alternating carbon and nitrogen atoms, creating a stable aromatic system. The chlorine atoms are attached to carbon atoms adjacent to nitrogen atoms, which increases the molecule’s electrophilic nature.
Because of this, the compound readily undergoes nucleophilic aromatic substitution (SNAr), allowing the replacement of chlorine atoms with other functional groups such as amines, alkoxides, or thiols.
This reactivity forms the foundation for its use in synthesizing a variety of substituted pyrimidines—common scaffolds in modern medicinal chemistry.
Several routes exist for synthesizing 2,4-dichloropyrimidine, but the most widely used methods include:
(a) Chlorination of Pyrimidine Precursors
Direct chlorination of pyrimidine or dihydropyrimidine derivatives using reagents such as phosphorus oxychloride (POCl₃) or thionyl chloride (SOCl₂) in the presence of catalysts.
The reaction typically proceeds under controlled temperature conditions (90–120 °C), yielding 2,4-dichloropyrimidine with high purity.
(b) Ring Construction Approach
Another approach involves constructing the pyrimidine ring from precursors like malononitrile and formamide, followed by chlorination.
This route is preferred for large-scale synthesis due to better yield and fewer by-products.
Property |
Value |
|---|---|
Molecular Formula |
C₄H₂Cl₂N₂ |
Molecular Weight |
165.98 g/mol |
Boiling Point |
184–186 °C |
Melting Point |
43–46 °C |
Density |
1.41 g/cm³ |
Solubility |
Soluble in organic solvents like ethanol, ether, and chloroform; slightly soluble in water |
Stability |
Stable under normal conditions; hydrolyzes slowly in moisture |
These properties make it easy to store and handle in laboratory and industrial environments, provided standard safety measures are followed.
2,4-Dichloropyrimidine serves as a key intermediate in drug synthesis, particularly for molecules containing pyrimidine rings—a core structure in many antiviral, anticancer, and anti-inflammatory drugs.
Examples include:
Antiviral agents (e.g., HIV reverse transcriptase inhibitors)
Kinase inhibitors used in cancer therapy
Antibacterial compounds where pyrimidine scaffolds enhance bioactivity
In the agrochemical industry, 2,4-dichloropyrimidine is used to produce herbicides, fungicides, and insecticides.
Its ability to form stable yet reactive intermediates allows manufacturers to develop compounds with improved selectivity and environmental compatibility.
Some specialty dyes and optical brighteners incorporate pyrimidine-based frameworks derived from this compound, enhancing brightness and stability under UV light.
In advanced materials research, 2,4-dichloropyrimidine is used in the functionalization of polymers and nanomaterials to introduce nitrogen-rich coordination sites or electron-withdrawing groups for electronic and optical applications.
Like most chlorinated heterocycles, 2,4-dichloropyrimidine should be handled with care:
Avoid skin or eye contact; use gloves and protective eyewear.
Work in a well-ventilated fume hood to minimize inhalation.
Store in tightly closed containers, away from moisture and strong oxidizers.
Dispose of according to local hazardous waste regulations.
Hazard classification: Irritant; may cause skin and respiratory tract irritation upon exposure.
As the demand for heterocyclic building blocks continues to grow in pharmaceutical and materials chemistry, compounds like 2,4-Dichloropyrimidine will remain essential.
Recent advancements in green synthesis and microwave-assisted chlorination techniques are making production more efficient and environmentally friendly.
Emerging research focuses on using this compound as a starting material for pyrimidine-based drug discovery, opening new possibilities for therapeutic innovation in 2025 and beyond.
2,4-Dichloropyrimidine (CAS 3934-20-1) exemplifies the importance of small yet highly functionalized heterocyclic compounds in modern chemistry. Its dual chlorine substitutions provide exceptional versatility, allowing chemists to design a broad range of bioactive and functional molecules.
From drug development to agrochemical synthesis, this compound’s relevance continues to grow—underscoring its role as a cornerstone in both academic and industrial chemical research.
