5-(Bromomethyl)-2-methoxypyridine Hydrobromide: Key FAQs

5-(Bromomethyl)-2-methoxypyridine hydrobromide is a reactive heterocyclic alkylating agent used as a versatile building block in organic synthesis, providing a pyridine-bearing benzylic bromide electrophile in a stable, isolable hydrobromide salt form.

Product SKU

B1341177

Chemical Name

5-(Bromomethyl)-2-methoxypyridine hydrobromide

Functional Class

Benzylic bromide electrophile / heterocyclic alkylating agent

Salt Form

Hydrobromide salt (improves solid-state stability relative to free base)

Key Reactive Site

Benzylic C–Br bond at the 5-position of the methoxypyridine ring

Primary Application

N-alkylation, O-alkylation, C-alkylation, and cross-coupling precursor synthesis

What Is 5-(Bromomethyl)-2-methoxypyridine Hydrobromide?

5-(Bromomethyl)-2-methoxypyridine hydrobromide (Aladdin SKU: B1341177) is a pyridine-based heterocyclic compound carrying a bromomethyl (–CH₂Br) group at the 5-position and a methoxy (–OCH₃) group at the 2-position of the pyridine ring. It is supplied as a hydrobromide salt, which confers improved solid-state stability and ease of handling compared with the corresponding free base.

The compound belongs to the class of benzylic bromide electrophiles. Because the bromomethyl group is activated by the adjacent electron-deficient pyridine ring, the C–Br bond is highly reactive toward nucleophilic substitution, making this reagent a valuable building block for introducing the 2-methoxypyridin-5-ylmethyl fragment into target molecules.

How Should This Reagent Be Stored and Handled?

As an alkyl bromide and a hydrobromide salt, 5-(Bromomethyl)-2-methoxypyridine hydrobromide should be stored in a cool, dry, well-ventilated location away from light, moisture, and incompatible materials such as strong bases and strong nucleophiles. Refrigerated storage (2–8 °C) under an inert atmosphere (nitrogen or argon) in a tightly sealed container is recommended to minimise hydrolysis and decomposition of the benzylic bromide functionality.

Standard laboratory precautions for alkyl bromide reagents apply: wear appropriate personal protective equipment (gloves, eye protection, lab coat), work in a fume hood, and consult the Safety Data Sheet (SDS) before use. Avoid prolonged skin contact or inhalation of dust or vapours.

Note: Specific stability data and shelf-life figures are not provided in the available product documentation. Researchers should verify current lot-specific certificates of analysis supplied with the product.

What Are the Main Synthetic Applications?

The highly electrophilic benzylic bromide moiety in 5-(Bromomethyl)-2-methoxypyridine hydrobromide enables a broad range of synthetic transformations:

• N-Alkylation: Reaction with amines, nitrogen heterocycles, or azide anions to install the methoxypyridylmethyl group on nitrogen-containing nucleophiles.
• O-Alkylation: Etherification with alcohols or phenols under basic conditions.
• C-Alkylation: Reaction with stabilised carbanions (malonates, active methylene compounds) to form new C–C bonds.
• Phosphonium salt formation: Treatment with triphenylphosphine to yield a phosphonium salt suitable for Wittig-type chemistry.
• Precursor to organolithium or Grignard reagents: Metal–halogen exchange can be considered under appropriate conditions.

The 2-methoxy substituent on the pyridine ring can also serve as a handle for further functionalisation, for example via demethylation to reveal a hydroxypyridine or pyridinone moiety.

How Is the Hydrobromide Salt Handled in Reactions?

Because the reagent is supplied as a hydrobromide salt, the protonated amine (if any free-base amine character were present) or the acid component must be accounted for in reaction stoichiometry. For most alkylation reactions where the bromomethyl group is the reactive electrophile, the hydrobromide salt can often be used directly without prior free-basing, provided that the reaction conditions include a suitable base (e.g., K₂CO₃, Cs₂CO₃, Et₃N, or DIPEA) to neutralise the HBr released during the reaction.

If the free base form is required, careful treatment with a mild base (e.g., aqueous Na₂CO₃ followed by extraction into an organic solvent) can be used, although the free benzylic bromide may be more prone to decomposition and should be used promptly after liberation.

Caution: Specific free-basing protocols for this compound have not been validated in the available source material. Researchers should optimise conditions based on their specific reaction requirements.

How to Order and What to Expect from Aladdin Scientific

5-(Bromomethyl)-2-methoxypyridine hydrobromide is available from Aladdin Scientific under SKU B1341177. Orders can be placed through the Aladdin Scientific website or by contacting the sales team directly. Product documentation, including the certificate of analysis (CoA) and safety data sheet (SDS), is available upon request or via the product page.

For bulk quantities, custom packaging, or specific purity requirements, contact Aladdin Scientific customer service. Lot-specific analytical data (e.g., NMR, HPLC purity, melting point) should be reviewed prior to use to confirm the material meets experimental requirements.

Frequently asked questions

What nucleophiles react well with 5-(Bromomethyl)-2-methoxypyridine hydrobromide?

The activated benzylic bromide undergoes efficient S_N2 reactions with a wide range of nucleophiles, including primary and secondary amines, phenolates and alkoxides (O-alkylation), stabilised carbanions such as malonates, azides, thiols, and thiolates. Softer nucleophiles generally react rapidly owing to the enhanced electrophilicity imparted by the electron-withdrawing pyridine ring.

Does the hydrobromide salt affect the reactivity of the bromomethyl group?

The hydrobromide counterion is not covalently bonded to the bromomethyl carbon and does not directly reduce its electrophilicity. However, when using the salt in reactions, an additional equivalent of base must be included to neutralise the HBr. Failure to account for the extra acid may reduce yields by protonating the nucleophile or shifting the reaction equilibrium unfavourably.

What solvents are suitable for reactions using this reagent?

Polar aprotic solvents such as DMF, DMSO, acetonitrile, and THF are commonly employed for S_N2 alkylation reactions with benzylic bromides, as they solvate cations effectively without deactivating the nucleophile. The choice of solvent will also depend on the solubility of the hydrobromide salt and the nucleophilic partner. Consult the experimental literature for optimised conditions relevant to specific transformations.

Is 5-(Bromomethyl)-2-methoxypyridine hydrobromide air- and moisture-sensitive?

Benzylic bromide compounds are generally susceptible to hydrolysis in the presence of moisture, forming the corresponding benzyl alcohol and HBr. Although the hydrobromide salt form provides some additional physical stability relative to the free base, prolonged exposure to atmospheric moisture should be avoided. Short-term bench handling is typically feasible, but the reagent should be stored sealed under inert gas when not in use.

Can this reagent be used in cross-coupling reactions?

Benzylic bromides can in principle participate in transition-metal-catalysed cross-coupling reactions (e.g., Suzuki, Negishi, or Kumada couplings) as the electrophilic coupling partner, although benzylic halides may require careful optimisation of catalyst, ligand, and conditions to suppress side reactions such as homo-coupling or elimination. The 2-methoxypyridine motif may also coordinate to metal centres, which could influence catalytic outcomes and should be considered during reaction design.

References

1. March, J.; Smith, M. B. March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 7th ed.; Wiley: Hoboken, NJ, 2013. (General reference for S_N2 reactivity of benzylic halides.)
2. Aladdin Scientific product page for 5-(Bromomethyl)-2-methoxypyridine hydrobromide, SKU B1341177. (Primary source for product identity and availability.)

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