2-Chloromethyl-3,4-dimethoxypyridinium chloride
[CAS# 72830-09-2]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyridine compound >> Pyridine derivative
• Name: 2-Chloromethyl-3,4-dimethoxypyridinium chloride
• Synonyms: 2-(Chloromethyl)-3,4-dimethoxypyridinium hydrochloride
• Molecular Formula: C₈H₁₁Cl₂NO₂
• Molecular Weight: 224.08
• CAS Registry Number: 72830-09-2
• EC Number: 416-440-5
• SMILES: COC1=C(C(=NC=C1)CCl)OC.Cl

Properties

• Melting point: 155 °C (Decomposes) (Expl.)

Safety Data

• Hazard Symbols: GHS05;GHS07;GHS08;GHS09 Danger
• Risk Statements: H302-H312:-H315:-H317:-H318:-H373-H411:
• Safety Statements: P260-P261-P264-P264+P265-P270-P272-P273-P280-P301+P317-P302+P352-P305+P354+P338-P317-P319-P321-P330-P332+P317-P333+P317-P362+P364-P391-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin irritation	Skin Irrit.	2	H315
Skin sensitization	Skin Sens.	1	H317
Serious eye damage	Eye Dam.	1	H318
Acute toxicity	Acute Tox.	4	H302
Specific target organ toxicity - repeated exposure	STOT RE	2	H373
Acute toxicity	Acute Tox.	4	H312
Chronic hazardous to the aquatic environment	Aquatic Chronic	2	H411

• Transport Information: UN 3077

Discovery and Applications

2-Chloromethyl-3,4-dimethoxypyridinium chloride is a synthetic heterocyclic salt characterized by a pyridinium core substituted with chloromethyl and methoxy groups. The molecular formula is C₈H₁₁Cl₂NO₂. The structure includes a positively charged nitrogen atom in the pyridine ring, giving it pyridinium salt properties, with chlorine present both as a substituent (chloromethyl group at position 2) and as a counterion (chloride ion).

This compound is primarily used as a reactive intermediate in organic synthesis, particularly in the preparation of functionalized pyridine derivatives and as an alkylating agent. The chloromethyl substituent is an electrophilic site that readily undergoes nucleophilic substitution reactions, allowing for the introduction of various nucleophiles such as amines, thiols, or alcohols. The 3,4-dimethoxy groups influence the electronic properties of the pyridinium ring, enhancing its stability and reactivity.

In synthetic organic chemistry, 2-chloromethyl-3,4-dimethoxypyridinium chloride serves as a useful building block for the synthesis of bioactive molecules, pharmaceuticals, and agrochemicals. Its reactivity profile facilitates the construction of more complex heterocyclic structures through subsequent substitution or coupling reactions. The presence of electron-donating methoxy groups on the aromatic ring can modulate the compound’s chemical behavior, making it a versatile reagent in multi-step synthesis.

This compound is related structurally and functionally to other pyridinium salts used as coupling reagents, such as the Mukaiyama reagent or Vilsmeier-type reagents, which are important in activating carbonyl groups or facilitating the formation of amides and esters. Its specific substitution pattern can affect its reactivity and selectivity in these processes.

Due to the presence of the electrophilic chloromethyl group and the charged pyridinium center, 2-chloromethyl-3,4-dimethoxypyridinium chloride must be handled carefully. It is generally stable as a crystalline solid under dry conditions but can react violently with nucleophiles or moisture. Proper laboratory precautions including use of gloves, eye protection, and working in a fume hood are recommended.

In summary, 2-chloromethyl-3,4-dimethoxypyridinium chloride is a synthetic pyridinium salt used as a reactive intermediate and alkylating agent in organic synthesis. Its electrophilic chloromethyl substituent and electron-rich aromatic ring make it valuable for constructing complex heterocycles and bioactive molecules in pharmaceutical and agrochemical research.

References

2014. fac-Cobalt(III)-azido complexes derived from substituted pyridyl-based tridentate amines. Transition Metal Chemistry, 39(6).
DOI: 10.1007/s11243-014-9837-6

2008. Validated Chromatographic Methods for the Determination of Process Related Toxic Impurities in Pantoprazole Sodium. Chromatographia, 68(5-6).
DOI: 10.1365/s10337-008-0718-z

2003. Pantoprazole sodium. Pharmaceutical Substances.
URL: https://pharmaceutical-substances.thieme.com/ps/search-results?docUri=KD-16-0006