2-Chloro-6-methoxypyrazine: Properties, Uses & FAQs

2-Chloro-6-methoxypyrazine is a halogenated, methoxy-substituted pyrazine heterocycle widely employed as a versatile building block in pharmaceutical synthesis, agrochemical research, and medicinal chemistry.

CAS Number

38557-72-1

Molecular Formula

C5H5ClN2O

Molecular Weight

144.56 g/mol

Aladdin SKU

C192788

Appearance

White to off-white crystalline solid

Key Functional Groups

Aryl chloride, methoxy group, pyrazine ring

What Is 2-Chloro-6-methoxypyrazine?

2-Chloro-6-methoxypyrazine (CAS 38557-72-1; Aladdin SKU C192788) is a disubstituted pyrazine bearing a chloro substituent at the 2-position and a methoxy group at the 6-position. The pyrazine core is a six-membered aromatic heterocycle containing two nitrogen atoms at the 1- and 4-positions, which confers electron-deficient character to the ring. This electron deficiency, combined with the activating influence of the methoxy group and the leaving-group ability of the chloro substituent, makes the molecule an excellent electrophilic partner in nucleophilic aromatic substitution (SNAr) reactions and a reliable substrate for transition-metal-catalyzed cross-coupling reactions such as Suzuki-Miyaura, Buchwald-Hartwig, and Negishi couplings.

The compound is commercially available as a white to off-white crystalline solid with a molecular formula of C5H5ClN2O and a molecular weight of 144.56 g/mol. It serves as a key pharmaceutical intermediate and agrochemical building block, enabling rapid construction of complex pyrazine-containing architectures from a single, stable starting material.

Synthetic Applications and Reactivity

The dual functionality of 2-Chloro-6-methoxypyrazine makes it particularly attractive for medicinal chemists. The C–Cl bond is amenable to a broad range of transformations:

• Nucleophilic Aromatic Substitution (SNAr): Amines, alkoxides, and thiolates can displace the chloride under mild conditions, producing 2-amino-, 2-alkoxy-, or 2-thioether-substituted methoxypyrazines. The electron-withdrawing pyrazine nitrogens activate the ring toward SNAr.
• Palladium-Catalyzed Cross-Coupling: The aryl chloride participates in Suzuki-Miyaura (boronic acids), Negishi (organozinc), and Buchwald-Hartwig (amination) reactions using appropriate palladium catalyst systems. Bulky phosphine ligands (e.g., SPhos, XPhos) are typically required to activate the less-reactive C–Cl bond relative to aryl bromides or iodides.
• Methoxy Group Manipulation: The methoxy group can be selectively demethylated (e.g., with BBr3 or TMSI) to afford 2-chloro-6-hydroxypyrazine, or retained as a directing or blocking group in further functionalization sequences.

These features collectively make 2-Chloro-6-methoxypyrazine a convergent building block for constructing drug-like heterocyclic scaffolds, particularly in kinase inhibitor, antiviral, and antibacterial programs.

Handling, Storage, and Safety

Although 2-Chloro-6-methoxypyrazine is a relatively stable crystalline solid under normal laboratory conditions, standard precautions for handling halogenated heterocycles should be observed:

• Personal Protective Equipment (PPE): Wear nitrile gloves, safety goggles, and a lab coat. Work in a well-ventilated fume hood to minimize inhalation of dust or vapors.
• Storage: Store in a tightly sealed container in a cool, dry, dark location (recommended 2–8 °C or room temperature as specified on the Certificate of Analysis). Avoid prolonged exposure to moisture, light, and air, which may cause slow degradation over time.
• Stability: The compound is stable under recommended storage conditions. The aryl chloride bond is resistant to hydrolysis under ambient conditions but may react slowly with strong nucleophiles over extended storage periods.
• Disposal: Dispose of waste material in accordance with local, national, and institutional regulations for halogenated organic compounds.

Always consult the Safety Data Sheet (SDS) provided by Aladdin Scientific before use. Specific hazard classifications, first-aid measures, and regulatory information are detailed therein.

Purity, Quality, and Analytical Specifications

For research-grade applications, purity is a critical parameter. Aladdin Scientific supplies 2-Chloro-6-methoxypyrazine (SKU C192788) with purity specifications verified by established analytical methods. Researchers should review the Certificate of Analysis (CoA) accompanying each lot for the following key quality attributes:

• Purity (GC or HPLC): Typical research-grade lots are supplied at ≥97% or ≥98% purity; confirm exact specification on the lot-specific CoA.
• Identity Confirmation: Structural identity is routinely confirmed by NMR spectroscopy (1H and 13C) and/or mass spectrometry (MS). Key 1H NMR features include two characteristic pyrazine ring proton singlets and the methoxy singlet (~3.9 ppm).
• Appearance: White to off-white crystalline or powdered solid; discoloration may indicate degradation.
• Water Content: Karl Fischer titration may be used to confirm suitability for moisture-sensitive reactions.

If your application demands higher purity (e.g., ≥99% for reference standard use), contact Aladdin Scientific's technical team to inquire about available grades or custom purification options.

Ordering and Availability

2-Chloro-6-methoxypyrazine is available from Aladdin Scientific under SKU C192788. To place an order or request a quotation:

• Visit the Aladdin Scientific website and search by product name or SKU C192788.
• Select the required pack size and quantity; multiple pack sizes may be available to suit screening, scale-up, or bulk needs.
• Download the current Safety Data Sheet (SDS) and Certificate of Analysis (CoA) directly from the product page prior to use.
• For bulk quantities, custom packaging, or special purity requirements, contact the Aladdin Scientific sales or technical support team directly.

Aladdin Scientific maintains inventory of commonly requested building blocks to support fast dispatch. Lead times for non-stock quantities may vary; contact customer service for current availability and delivery estimates.

Frequently asked questions

What reactions is 2-Chloro-6-methoxypyrazine commonly used for?

2-Chloro-6-methoxypyrazine is primarily used in nucleophilic aromatic substitution (SNAr) with amines, alkoxides, or thiolates, and in palladium-catalyzed cross-coupling reactions including Suzuki-Miyaura, Buchwald-Hartwig amination, and Negishi coupling. These transformations enable efficient construction of diverse pyrazine-containing heterocyclic scaffolds for pharmaceutical and agrochemical research.

How should 2-Chloro-6-methoxypyrazine be stored to maintain stability?

The compound should be stored in a tightly sealed container in a cool, dry, and dark environment, typically at 2–8 °C or at room temperature as specified on the lot Certificate of Analysis. It should be protected from moisture, prolonged light exposure, and air. Under these recommended conditions, the compound is stable for extended periods.

What is the purity of 2-Chloro-6-methoxypyrazine supplied by Aladdin Scientific?

Aladdin Scientific supplies 2-Chloro-6-methoxypyrazine (SKU C192788) at research-grade purity, typically ≥97% as determined by GC or HPLC. The exact purity specification for each lot is stated on the accompanying Certificate of Analysis, which can be downloaded from the product page on the Aladdin Scientific website.

Can the chloro group in 2-Chloro-6-methoxypyrazine be selectively functionalized in the presence of the methoxy group?

Yes. The C–Cl bond is selectively reactive under both SNAr and cross-coupling conditions, while the methoxy group remains largely inert under typical reaction conditions. This chemoselectivity allows the chloro position to be transformed first, after which the methoxy group can subsequently be manipulated (e.g., demethylated) if required, providing excellent orthogonal reactivity for multi-step synthesis.

Is a Safety Data Sheet (SDS) available for 2-Chloro-6-methoxypyrazine?

Yes, a Safety Data Sheet (SDS) for 2-Chloro-6-methoxypyrazine (SKU C192788) is available for download directly from the product listing on the Aladdin Scientific website. Researchers should consult the SDS before handling the compound to familiarize themselves with hazard classifications, first-aid measures, PPE requirements, and proper disposal procedures.

References

1. General reference: Smith, M. B. March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 8th ed. Wiley, 2019. (Nucleophilic aromatic substitution and cross-coupling reactions of aryl halides.)
2. Negishi, E. Handbook of Organopalladium Chemistry for Organic Synthesis. Wiley-Interscience, 2002. (Palladium-catalyzed cross-coupling methodologies applicable to aryl chlorides.)
3. Aladdin Scientific Product Page: 2-Chloro-6-methoxypyrazine, SKU C192788. https://www.aladdin-e.com (Certificate of Analysis and SDS available on request.)

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