2-(Chloro(4-chlorophenyl)methyl)pyridine: Properties & Uses

2-(Chloro(4-chlorophenyl)methyl)pyridine is a bifunctional halogenated organic intermediate featuring both a reactive benzylic chloride and a pyridine ring, making it a versatile building block for medicinal chemistry and fine chemical synthesis.

CAS / Product SKU

C190886 (Aladdin SKU); confirm CAS with SDS

Molecular Formula

C₁₂H₉Cl₂N

Molecular Weight

238.11 g/mol (calculated)

Key Functional Groups

Benzylic C–Cl, pyridyl ring (2-position substitution), aryl C–Cl (para)

Primary Application

Reactive electrophilic intermediate for N-alkylation, C–C coupling, and nucleophilic substitution reactions

Storage Recommendation

Store in a cool, dry, well-ventilated area away from moisture and incompatible oxidizers; confirm exact conditions on SDS

Chemical Identity and Structure

2-(Chloro(4-chlorophenyl)methyl)pyridine is an organochlorine compound that consists of a pyridine ring bearing a chloro(4-chlorophenyl)methyl substituent at the 2-position. This architecture places two distinct chlorine atoms in the molecule: one as a reactive benzylic chloride at the sp³ carbon bridging the pyridine and the 4-chlorophenyl ring, and a second as an aryl chloride on the para position of the phenyl ring.

The molecular formula is C₁₂H₉Cl₂N with a calculated molecular weight of approximately 238.11 g/mol. The benzylic position is activated toward nucleophilic displacement by the adjacent electron-withdrawing pyridine nitrogen, making the benzylic C–Cl bond significantly more electrophilic than a simple benzyl chloride. The aryl chloride, by contrast, is comparatively inert under mild conditions but can participate in transition-metal-catalysed cross-coupling reactions.

Note: Researchers should confirm CAS number, exact purity, and physical constants (melting point, appearance) from the Aladdin Certificate of Analysis for lot C190886 prior to use.

Synthesis and Reactivity

Compounds of the chloro(aryl)(2-pyridyl)methane class are typically accessible via chlorination of the corresponding carbinol precursor — in this case, (4-chlorophenyl)(pyridin-2-yl)methanol — using reagents such as thionyl chloride (SOCl₂) or oxalyl chloride under anhydrous conditions. The reaction proceeds through an intermediate chlorosulfite ester that collapses to yield the benzylic chloride with inversion or racemisation depending on solvent and conditions.

In terms of downstream reactivity, the activated benzylic chloride undergoes:

• S_N2 reactions with amines, thiols, alcohols, and soft carbon nucleophiles (e.g., malonates, enolates), enabling rapid library synthesis of new chemical entities.
• N-Alkylation of nitrogen heterocycles, useful for preparing quaternary ammonium salts or tertiary amines relevant to CNS-active compound series.
• Transition-metal-catalysed coupling: the aryl C–Cl bond can engage in Suzuki–Miyaura, Negishi, or Buchwald–Hartwig couplings under appropriate palladium catalysis, providing access to biaryl or aminoaryl analogues.

Review flag: Specific reaction yields, conditions, and literature precedents should be verified against primary sources before inclusion in experimental protocols.

Applications in Medicinal and Fine Chemistry

The structural motif of a (2-pyridyl)(4-chlorophenyl)methyl group is present in or related to several pharmacologically relevant scaffolds. Combining a Lewis-basic pyridine nitrogen with a lipophilic chlorophenyl group confers useful physicochemical properties such as moderate lipophilicity (log P typically in the 2–4 range for analogues, though specific values for this compound require experimental determination) and the capacity for metal coordination or hydrogen-bond acceptance.

Potential application areas include:

• Antihistamine and CNS research: Diarylmethyl and diarylmethylamine motifs are well represented in first- and second-generation antihistamines. This intermediate could serve as a precursor to amine-containing analogues via nucleophilic displacement.
• Kinase inhibitor scaffolds: Pyridine-containing diarylmethyl fragments appear in kinase inhibitor programmes; the aryl chloride handle enables diversification via cross-coupling.
• Agrochemical research: Halogenated pyridine-aryl intermediates are also employed in the synthesis of fungicides and insecticides.

Review flag: Specific pharmacological data or drug-candidate citations have not been provided in the source material and must not be implied without primary literature support.

Safety, Handling, and Storage

As a benzylic chloride, 2-(Chloro(4-chlorophenyl)methyl)pyridine should be treated as a lachrymatory and potentially irritating reagent. Standard precautions for reactive alkyl halides apply:

• Personal protective equipment (PPE): Chemical-splash goggles, nitrile gloves, and a laboratory coat are the minimum requirements. Handling should be performed in a fume hood.
• Moisture sensitivity: Benzylic chlorides can undergo hydrolysis on contact with water; keep the reagent sealed and store under dry conditions.
• Incompatibilities: Strong oxidisers, strong bases, and water should be avoided. Reactions with amines should be conducted with controlled addition to manage exothermicity.
• Waste disposal: Follow institutional and local regulations for halogenated organic waste disposal.

Always consult the current Safety Data Sheet (SDS) supplied by Aladdin for lot-specific hazard classifications, GHS pictograms, first-aid measures, and regulatory information before handling product C190886.

Analytical Characterisation and Quality Considerations

Researchers receiving lot C190886 should verify identity and purity using standard analytical techniques prior to use in critical syntheses:

• ¹H NMR spectroscopy: Expected signals include aromatic protons of the pyridine ring (4H, multiplets in the δ 7.2–8.6 ppm region), aromatic protons of the 4-chlorophenyl ring (4H, AA'BB' pattern), and the characteristic benzylic methine proton (1H, singlet, typically δ 6.0–6.5 ppm for analogous α-chloro benzylic protons). Exact chemical shifts should be confirmed against the Aladdin CoA.
• ¹³C NMR / Mass spectrometry: A molecular ion cluster consistent with two chlorine atoms (M, M+2, M+4 in approximately 9:6:1 ratio) confirms the molecular formula C₁₂H₉Cl₂N.
• HPLC purity: Request the Certificate of Analysis for lot-specific purity data. Purity ≥95% (by HPLC) is typically expected for synthetic-grade intermediates.
• Karl Fischer titration: Recommended if moisture-sensitive downstream reactions are planned.

Review flag: Specific NMR chemical shift values listed here are estimates based on analogue compounds and must be cross-checked against experimentally acquired spectra or the Aladdin CoA.

Frequently asked questions

What is 2-(Chloro(4-chlorophenyl)methyl)pyridine used for in research?

It is primarily used as an electrophilic building block in organic synthesis. The reactive benzylic chloride enables rapid introduction of the (4-chlorophenyl)(pyridin-2-yl)methyl pharmacophore via Sₙ2 reactions with amines, thiols, and carbon nucleophiles, while the aryl chloride supports palladium-catalysed cross-coupling for further structural diversification.

How should 2-(Chloro(4-chlorophenyl)methyl)pyridine be stored to maintain stability?

The compound should be stored in a tightly sealed container in a cool, dry, and well-ventilated location, away from moisture, water, and incompatible materials such as strong oxidisers. Exposure to humidity can cause hydrolysis of the benzylic chloride. Always refer to the current Aladdin SDS for lot-specific storage conditions.

Is 2-(Chloro(4-chlorophenyl)methyl)pyridine hazardous, and what PPE is required?

As a benzylic chloride, it is expected to be irritating to skin, eyes, and the respiratory tract and may have lachrymatory properties. At minimum, chemical-splash goggles, nitrile gloves, and a laboratory coat should be worn, and all handling should be performed in a fume hood. Consult the Aladdin SDS for the full GHS hazard classification and first-aid procedures specific to this product.

How can I confirm the identity and purity of lot C190886 upon receipt?

Request the Certificate of Analysis (CoA) from Aladdin, which provides lot-specific purity (typically by HPLC), appearance, and any available spectral data. You can further confirm identity by ¹H NMR — looking for the characteristic benzylic methine singlet and the two sets of aromatic protons — and by mass spectrometry, where the twin-chlorine isotope pattern in the molecular ion cluster serves as a diagnostic confirmation.

Can the aryl chloride in this compound be used in Suzuki cross-coupling reactions?

Yes, aryl chlorides can participate in Suzuki–Miyaura coupling under palladium catalysis, typically requiring more active catalyst systems (e.g., Pd with bulky phosphine or NHC ligands) than aryl bromides or iodides. The benzylic chloride may need protection or selective reactivity management during such transformations. Specific conditions should be optimised and validated in your laboratory.

References

1. Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed.; Oxford University Press: Oxford, 2012. (General reference for nucleophilic substitution and benzylic halide reactivity)
2. Miyaura, N.; Suzuki, A. Palladium-Catalyzed Cross-Coupling Reactions of Organoboron Compounds. Chem. Rev. 1995, 95, 2457–2483. doi:10.1021/cr00039a007
3. Aladdin Scientific. Certificate of Analysis, Product C190886, 2-(Chloro(4-chlorophenyl)methyl)pyridine. Aladdin Scientific Corp. (lot-specific; request from supplier).

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