1. Product Overview
2-Chloro-6-fluorobenzaldehyde (CAS: 98591-38-9) is an ortho-halogenated benzaldehyde derivative with the molecular formula C₇H₄ClFO and a molecular weight of 158.56 g/mol. This compound features a benzene ring bearing an aldehyde group at the 1-position, a chlorine atom at the 2-position, and a fluorine atom at the 6-position (ortho to both the aldehyde and the chlorine). At room temperature it typically appears as a colorless to pale yellow liquid or low-melting solid (melting point around 20–22 °C), with a characteristic aromatic/aldehydic odor.
The presence of the highly reactive aldehyde, combined with two orthogonal halogen substituents (Cl and F) on the aromatic ring, makes this a strategically valuable building block in organic synthesis. The aldehyde readily participates in condensations, reductions, and nucleophilic additions, while the ortho-chloro and para-fluoro halogens provide handles for selective cross-coupling or nucleophilic aromatic substitution, enabling stepwise scaffold elaboration in medicinal and agrochemical chemistry.
2. Key Features and Advantages
• Aldehyde + Di‑Halogen Motif: The formyl group allows immediate condensation (Schiff base formation with amines, Knoevenagel with active methylenes), reduction to alcohol or oxidation to acid, while Cl/F substituents support downstream Pd‑catalyzed couplings or SNAr.
• Ortho‑Substitution Pattern: 2‑Cl/6‑F arrangement creates steric and electronic effects useful for modulating reactivity and for constructing fused heterocycles via intramolecular cyclization after aldehyde functionalization.
• High Purity Grade: Typically supplied at ≥98% purity (GC/HPLC), suitable for sensitive pharmaceutical and fine‑chemical synthesis.
• Versatile Intermediate: Widely used in parallel library synthesis, API intermediate preparation, and agrochemical active ingredient development.
• Well‑Characterized: Standard analytical data (¹H/¹³C NMR, GC‑MS, IR for aldehyde C=O stretch ~1690–1720 cm⁻¹) routinely provided.
• Scalable Supply: Available from 1 g laboratory packs up to multi‑kilogram quantities for process R&D.
3. Main Applications
3.1 Pharmaceutical Intermediate
2‑Chloro‑6‑fluorobenzaldehyde is a key starting material for constructing bioactive small molecules:
• Schiff Base & Heterocycle Formation: Condensation with amines yields imines that can be reduced to secondary amines or cyclized to benzodiazepines, quinazolines, and indole derivatives used in kinase inhibitor and CNS drug discovery.
• Aldehyde‑Based Cyclizations: Reaction with hydrazines → pyrazoles; with hydroxylamine → oximes/isoxazoles; with malononitrile → Knoevenagel adducts that cyclize to coumarins or chromenes with antiparasitic/anticancer relevance.
• Fluorinated Pharmacophore: The 2‑Cl/6‑F pattern introduces metabolic stability and tuned lipophilicity (log P ~2.1 predicted) into derived APIs, valuable in designing fluorinated drug candidates.
3.2 Agrochemical Research
Halogenated benzaldehydes are foundational in crop‑protection chemistry:
• Used to synthesize fluorinated pyrethroid analogues, strobilurin‑type fungicides, and benzaldehyde‑derived herbicides via aldol/condensation routes.
• The aldehyde enables easy attachment of heterocyclic warheads (triazoles, oxadiazoles) common in modern pesticide design.
3.3 Organic Synthesis & Material Science
• Serves as a model substrate for studying ortho‑halogen effects on aromatic electrophilic substitution and on aldehyde‑directed ortho‑metalation (DoM).
• Employed in preparing fluorinated liquid‑crystal precursors and fluorescent dyes where the aldehyde is converted to styryl or azomethine linkages.
4. Technical Specifications
5. Storage and Handling
Storage Conditions
• Store in a cool, dry place at 2–8 °C in a tightly sealed container.
• Protect from light and air; aldehydes are prone to slow air oxidation to the corresponding benzoic acid and to photodegradation.
• Keep under inert atmosphere (argon or nitrogen) to minimize oxidation; use amber vials or foil wrapping.
• Store away from strong bases, strong oxidizers, and amines (will form imines on contact).
• For long‑term storage (>6 months), maintain under inert gas with desiccant; periodically check for acid formation by TLC/GC.
Handling Precautions
• Handle in a well‑ventilated area or fume hood to avoid inhalation of vapors/dust and skin contact.
• Aldehydes can be irritants; avoid direct contact with skin, eyes, and clothing.
• Use appropriate PPE as detailed in Section 6.
6. Safety Overview
Hazard Identification
• GHS Classification (typical supplier SDS): GHS07, Signal Word: Warning.
• Hazard Statements: H302 (Harmful if swallowed), H315 (Causes skin irritation), H319 (Causes serious eye irritation), H335 (May cause respiratory irritation).
• Intended strictly for industrial and scientific research use; not for human/veterinary therapeutic use, not for food/feed/cosmetic application.
• Aldehydes are potential sensitizers; prolonged exposure should be avoided.
First Aid Measures
• Inhalation: Move to fresh air. Seek medical attention if irritation or breathing difficulty persists.
• Skin Contact: Remove contaminated clothing. Rinse affected area thoroughly with soap and water.
• Eye Contact: Rinse immediately with plenty of running water for at least 15 minutes, holding eyelids open. Consult an ophthalmologist if irritation continues.
• Ingestion: Rinse mouth. Do NOT induce vomiting. Seek immediate medical attention.
Personal Protective Equipment (PPE)
• Eye/Face Protection: Safety goggles or face shield.
• Hand Protection: Nitrile chemical‑resistant gloves.
• Body Protection: Lab coat, long sleeves, closed‑toe shoes.
• Respiratory Protection: NIOSH‑approved organic vapor respirator or dust mask if handling generates aerosols/vapors.
Disposal Considerations
• Dispose of as hazardous chemical waste per local, regional, and national regulations.
• Do not discard in drains or release into the environment.
• Incinerate in a licensed chemical waste facility.
