2-Chloropyrimidine: Properties, Uses & Handling FAQ

2-Chloropyrimidine is a halogenated diazine building block widely employed in medicinal chemistry and materials science for the introduction of a pyrimidine ring via nucleophilic aromatic substitution reactions.

CAS Number

1722-12-9

Molecular Formula

C₄H₃ClN₂

Molecular Weight

114.53 g/mol

Appearance

White to off-white crystalline solid

Aladdin SKU

C132282

Primary Use

Electrophilic pyrimidine building block for SNAr reactions and cross-coupling

What Is 2-Chloropyrimidine and What Are Its Key Properties?

2-Chloropyrimidine (CAS 1722-12-9) is a six-membered nitrogen-containing heterocyclic compound belonging to the pyrimidine family. Its molecular formula is C₄H₃ClN₂ with a molecular weight of 114.53 g/mol. The compound features a pyrimidine ring with a chlorine substituent at the 2-position, flanked by the two ring nitrogen atoms at positions 1 and 3.

The presence of the two electron-withdrawing ring nitrogens activates the carbon bearing the chlorine toward nucleophilic aromatic substitution (SNAr), making the C–Cl bond considerably more reactive than a comparable chlorobenzene derivative. At room temperature, 2-Chloropyrimidine is a white to off-white crystalline solid. It is soluble in common organic solvents such as dichloromethane, ethanol, acetonitrile, and tetrahydrofuran, but has limited solubility in water.

What Are the Main Synthetic Applications of 2-Chloropyrimidine?

2-Chloropyrimidine is a versatile electrophilic building block used across multiple areas of synthetic chemistry:

• Nucleophilic Aromatic Substitution (SNAr): The electron-deficient pyrimidine ring undergoes facile displacement of chloride by oxygen, nitrogen, sulfur, and carbon nucleophiles. This allows straightforward access to 2-amino-, 2-alkoxy-, and 2-thio-pyrimidine derivatives, which are prevalent pharmacophores.
• Transition-Metal-Catalyzed Cross-Coupling: 2-Chloropyrimidine participates in palladium-catalyzed reactions such as Suzuki–Miyaura, Buchwald–Hartwig, and Negishi couplings, enabling the construction of biaryl and heteroaryl frameworks important in drug discovery.
• Pharmaceutical Intermediate: The pyrimidine core is found in numerous bioactive molecules, including kinase inhibitors, antiviral agents, and antimicrobials. 2-Chloropyrimidine serves as a key starting material or intermediate in the synthesis of such compounds.
• Materials Science: Pyrimidine-containing frameworks derived from 2-Chloropyrimidine are explored in the design of organic semiconductors and ligands for coordination chemistry.

How Should 2-Chloropyrimidine Be Stored and Handled Safely?

Storage: Store 2-Chloropyrimidine in a tightly sealed container in a cool, dry, and well-ventilated location, away from moisture, heat, and incompatible materials such as strong oxidizers, strong bases, and strong acids. Storage at 2–8 °C under inert atmosphere is recommended for long-term preservation of purity.

Handling Precautions: 2-Chloropyrimidine is classified as an irritant. It may cause irritation to the skin, eyes, and respiratory tract upon contact or inhalation. Always handle in a fume hood wearing appropriate personal protective equipment (PPE): nitrile gloves, safety goggles, and a lab coat. Avoid generating dust. In case of skin or eye contact, flush immediately with copious amounts of water and seek medical advice.

Waste Disposal: Dispose of waste material in accordance with local and national environmental regulations. Do not discharge into drains or the environment.

How Does 2-Chloropyrimidine Compare to Other Chloropyrimidine Isomers?

The chloropyrimidine isomers—2-chloro, 4-chloro, and 5-chloropyrimidine—differ in their reactivity and selectivity profiles due to the varying positions of the chlorine substituent relative to the ring nitrogen atoms.

2-Chloropyrimidine positions the chlorine symmetrically between both nitrogens, providing high electrophilic activation at C-2 and making it the most reactive of the common isomers toward SNAr. This symmetry also simplifies regioselectivity considerations in many reactions.

4-Chloropyrimidine places chlorine adjacent to one nitrogen, offering an activated but less symmetrical reactive site, which can provide useful chemoselectivity in multistep syntheses.

5-Chloropyrimidine bears the chlorine at a position not directly activated by the flanking nitrogens toward SNAr; it is therefore significantly less reactive in nucleophilic substitution but useful as a substrate for metal-catalyzed reactions.

The choice among isomers is dictated by the desired substitution pattern and the reactivity requirements of the target molecule.

Quality, Purity, and Ordering Information

Aladdin Scientific offers 2-Chloropyrimidine (SKU: C132282) as a research-grade reagent. Researchers should consult the product specification sheet (CoA) for the confirmed purity grade, analytical data (including GC or HPLC purity, melting point, and NMR), and batch-specific information before use.

When placing an order, verify that the required quantity and purity grade meet your experimental needs. For bulk or custom quantities, contact Aladdin's sales team. Proper documentation, including Safety Data Sheet (SDS), is available on the product page to support regulatory compliance in your laboratory.

For questions about compatibility, alternative grades, or technical support regarding 2-Chloropyrimidine, Aladdin's technical support team is available to assist.

Frequently asked questions

What is the CAS number for 2-Chloropyrimidine?

The CAS registry number for 2-Chloropyrimidine is 1722-12-9. This number uniquely identifies the compound and should be used when searching databases, placing orders, or citing the compound in publications.

Why is 2-Chloropyrimidine more reactive in SNAr reactions than chlorobenzene?

The two ring nitrogen atoms at positions 1 and 3 of the pyrimidine ring are strongly electron-withdrawing. This electron deficiency stabilizes the Meisenheimer complex intermediate formed during nucleophilic aromatic substitution, significantly lowering the activation energy compared to chlorobenzene, which lacks such activating groups. As a result, 2-Chloropyrimidine undergoes SNAr with a wide range of nucleophiles under mild conditions.

Can 2-Chloropyrimidine be used in palladium-catalyzed cross-coupling reactions?

Yes, 2-Chloropyrimidine is a competent electrophilic partner in palladium-catalyzed cross-coupling reactions, including Suzuki–Miyaura (with boronic acids), Buchwald–Hartwig (for C–N bond formation), and Negishi couplings (with organozinc reagents). Appropriate ligand selection is important to achieve good yields with aryl chloride substrates, as C–Cl bonds are generally less reactive than C–Br or C–I bonds in oxidative addition.

What solvents are suitable for reactions involving 2-Chloropyrimidine?

2-Chloropyrimidine dissolves readily in polar aprotic solvents such as DMF, DMSO, acetonitrile, and THF, making these suitable choices for SNAr and cross-coupling reactions. Dichloromethane and ethanol are also commonly used. Water should generally be avoided as the primary solvent due to limited solubility, though aqueous co-solvent systems may be applicable in specific cases.

How should I confirm the purity of the 2-Chloropyrimidine I receive from Aladdin?

Each batch of Aladdin's 2-Chloropyrimidine (SKU: C132282) is accompanied by a Certificate of Analysis (CoA) that details the purity (typically assessed by GC or HPLC), melting point, and other quality parameters. The CoA can be downloaded from the product page using the batch number printed on the label. If you require additional analytical verification, techniques such as ¹H NMR, ¹³C NMR, or mass spectrometry can be used to confirm identity and purity.

References

1. March, J.; Smith, M. B. March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 7th ed.; Wiley: Hoboken, NJ, 2013. (Chapter on Nucleophilic Aromatic Substitution)
2. Joule, J. A.; Mills, K. Heterocyclic Chemistry, 5th ed.; Wiley-Blackwell: Oxford, 2010. (Chapter on Pyrimidines)
3. Miyaura, N.; Suzuki, A. Palladium-Catalyzed Cross-Coupling Reactions of Organoboron Compounds. Chem. Rev. 1995, 95, 2457–2483. doi:10.1021/cr00039a007
4. Aladdin Scientific. 2-Chloropyrimidine Product Page, SKU C132282. https://www.aladdin-e.com

Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.