5-Acetyl-4,6-dichloropyrimidine
[CAS# 60025-06-1]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyrimidine compound >> Chloropyrimidine
• Name: 5-Acetyl-4,6-dichloropyrimidine
• Synonyms: 1-(4,6-dichloropyrimidin-5-yl)ethanone
• Molecular Formula: C₆H₄Cl₂N₂O
• Molecular Weight: 191.01
• CAS Registry Number: 60025-06-1
• EC Number: 848-964-9
• SMILES: CC(=O)C1=C(N=CN=C1Cl)Cl

Properties

• Solubility: Slightly soluble (4.2 g/L) (25 °C), Calc.^*
• Density: 1.454±0.06 g/cm³ (20 °C 760 Torr), Calc.^*
• Melting point: 90-91 °C^**
• Index of Refraction: 1.557, Calc.^*
• Boiling point: 240.3±35.0 °C (760 Torr), Calc.^*
• Flash point: 99.1±25.9 °C, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software V11.02 (©1994-2019 ACD/Labs)

^** Clark, Jim

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H315-H319-H335
• Safety 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
Specific target organ toxicity - single exposure	STOT SE	3	H335
Eye irritation	Eye Irrit.	2A	H319
Skin irritation	Skin Irrit.	2	H315

Discovery and Applications

5-Acetyl-4,6-dichloropyrimidine is an important heterocyclic compound that plays a key role in organic synthesis, particularly in the development of pharmaceuticals and agrochemicals. Structurally, it features a pyrimidine ring with chlorine substituents at the 4- and 6-positions and an acetyl group at the 5-position. This specific arrangement of functional groups provides the molecule with unique reactivity, allowing for a wide range of chemical transformations and applications.

The discovery and synthesis of 5-acetyl-4,6-dichloropyrimidine are linked to the broader exploration of pyrimidine derivatives in the early-to-mid 20th century. Pyrimidines are fundamental structures in organic chemistry due to their presence in nucleic acids, such as DNA and RNA, as well as various synthetic bioactive molecules. The introduction of electron-withdrawing chlorine atoms into the pyrimidine ring increases the compound’s electrophilic character, enhancing its potential as an intermediate in diverse chemical reactions.

In pharmaceutical chemistry, 5-acetyl-4,6-dichloropyrimidine serves as a valuable building block for the synthesis of antiviral, antibacterial, and anticancer agents. The presence of reactive chlorine atoms allows for selective nucleophilic substitution, enabling the attachment of different functional groups that can modify biological activity. For example, by substituting the chlorine atoms with amino or hydroxyl groups, chemists can create derivatives that exhibit enhanced pharmacological properties. Such modifications have led to the development of drugs targeting bacterial infections and viral diseases.

Agrochemical research has also benefited from 5-acetyl-4,6-dichloropyrimidine. Many modern pesticides, herbicides, and fungicides are based on pyrimidine structures, which can be tailored to improve efficacy and selectivity. The acetyl group at the 5-position provides a site for further chemical modifications, allowing the creation of compounds that effectively combat specific pests or plant diseases while minimizing environmental impact. The versatility of this compound in agrochemical synthesis lies in its ability to serve as a scaffold for various bioactive molecules.

Additionally, 5-acetyl-4,6-dichloropyrimidine is employed in the development of advanced materials. Pyrimidine derivatives have been explored for their potential in electronic and optical applications, such as organic light-emitting diodes (OLEDs) and liquid crystals. The electron-withdrawing chlorine atoms contribute to the compound’s ability to participate in π-conjugated systems, which are essential for such applications. Modifying the molecule with appropriate substituents can enhance its thermal and chemical stability, making it suitable for use in high-performance materials.

The synthesis of 5-acetyl-4,6-dichloropyrimidine typically involves chlorination of precursor pyrimidine compounds followed by acetylation at the 5-position. Common methods include the use of reagents such as phosphorus oxychloride or thionyl chloride for chlorination and acetyl chloride or acetic anhydride for acetylation. Advances in synthetic techniques have improved the yield and purity of this compound, making it more accessible for large-scale applications.

Research into the applications of 5-acetyl-4,6-dichloropyrimidine continues to expand as scientists explore new ways to harness its chemical properties. Its utility as a versatile intermediate in pharmaceutical, agrochemical, and material science ensures that it remains a valuable component in modern organic synthesis. The ongoing development of derivatives based on this compound reflects its importance in addressing challenges in medicine, agriculture, and technology.

References

2013. Reaction of Ethyl 3,3-Diaminoacrylate with Pyrimidine Series o-Chloro Ketones. Synthesis of Pyrido[4,3-d]Pyrimidines and 6H-1,3,6,7-Tetra-azaphenalenes. *Chemistry of Heterocyclic Compounds*, 49(3). DOI: 10.1007/s10593-013-1269-2

2007. Direction of Hydrolysis of Esters of Some Pyrimidine-5-Carboxylic Acids. *Chemistry of Heterocyclic Compounds*, 43(11). DOI: 10.1007/s10593-007-0228-1

1985. Pyrimidines. 75. Syntheses Based on Acetylpyrimidines. 4,6-Dihydroxy-5-Acetylpyrimidine and Preparation of 4',5-Bipyrimidines and Their Derivatives. *Chemistry of Heterocyclic Compounds*, 21(3). DOI: 10.1007/bf00506674