4-Chloro-2-fluoro-5-nitrophenol - ≥98% , CAS No.98404-02-5

CAS: 98404-02-5 Cat. No.: C979110 Summenformel: C₆H₃ClFNO₃ Molekulargewicht: 191.54 EG-Nummer: 185-476-9 PubChem CID: 18625319

GRADE & PURITY ≥98%

Storage

Room temperature

Specifications

Spezifikationen & Reinheit

≥98%

Storage

Room temperature

Reinheit

≥98%

Namen und Kennungen

• Kanonisches Lächeln: C1=C(C(=CC(=C1O)F)Cl)[N+](=O)[O-]
• IUPAC Name: 4-chloro-2-fluoro-5-nitrophenol
• InChIKey: DIIWMWNVGLVEFJ-UHFFFAOYSA-N
• INCHI: 1S/C6H3ClFNO3/c7-3-1-4(8)6(10)2-5(3)9(11)12/h1-2,10H
• Isomere SMILES: C1=C(C(=CC(=C1O)F)Cl)[N+](=O)[O-]
• PubChem CID: 18625319
• Molekulargewicht: 191.54

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Klasse Phenols
      • Subclass Nitrophenols

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Klasse: Phenols
• Subclass: Nitrophenols
• Intermediate Tree Nodes: Not available
• Direct Parent: Nitrophenols
• Alternative Parents: Nitrobenzenes P-chlorophenols Nitroaromatic compounds O-fluorophenols 1-hydroxy-2-unsubstituted benzenoids Chlorobenzenes Fluorobenzenes Aryl chlorides Aryl fluorides Propargyl-type 1,3-dipolar organic compounds Organic oxoazanium compounds Organooxygen compounds Organic oxides Hydrocarbon derivatives Organic salts Organochlorides Organofluorides Organonitrogen compounds Organic cations
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Nitrophenol - Nitrobenzene - 2-fluorophenol - Nitroaromatic compound - 4-chlorophenol - 2-halophenol - 4-halophenol - 1-hydroxy-2-unsubstituted benzenoid - Halobenzene - Fluorobenzene - Chlorobenzene - Monocyclic benzene moiety - Aryl halide - Aryl chloride - Aryl fluoride - Organic nitro compound - C-nitro compound - Organic 1,3-dipolar compound - Propargyl-type 1,3-dipolar organic compound - Allyl-type 1,3-dipolar organic compound - Organic oxoazanium - Organonitrogen compound - Organooxygen compound - Organic oxygen compound - Organic nitrogen compound - Organic salt - Hydrocarbon derivative - Organofluoride - Organochloride - Organohalogen compound - Organic oxide - Organic cation - Aromatic homomonocyclic compound
• Beschreibung: This compound belongs to the class of organic compounds known as nitrophenols. These are compounds containing a nitrophenol moiety, which consists of a benzene ring bearing both a hydroxyl group and a nitro group on two different ring carbon atoms.
• External Descriptors: Not available

Data sources

1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61.

DOI: 10.1186/s13321-016-0174-y

Chemische und physikalische Eigenschaften

• Molekulargewicht: 191.540 g/mol
• XLogP3: 2.000
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 0
• Exact Mass: 190.979 Da
• Monoisotopic Mass: 190.979 Da
• Topological Polar Surface Area: 66.100 Ų
• Heavy Atom Count: 12
• Formal Charge: 0
• Complexity: 186.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 0
• Undefined Atom Stereocenter Count: 0
• Defined Bond Stereocenter Count: 0
• Undefined Bond Stereocenter Count: 0
• The total count of all stereochemical bonds: 0
• Covalently-Bonded Unit Count: 1

Application Protocols

No biological assay or immunoassay protocols are specified for this small-molecule reagent. Typical use involves organic synthesis workflows:

• Dissolution: Charge to a dry flask; dissolve/suspend in a suitable solvent (e.g., DMF, DMSO, MeCN, dioxane) under inert atmosphere if moisture-sensitive reagents will be added.
• Base addition: Introduce base slowly with cooling if forming the phenolate or initiating SNAr.
• Reaction monitoring: Track by TLC, HPLC, or LC–MS; quench with controlled acidification to recover neutral phenol if needed.

For detailed, reaction-specific procedures, consult the synthetic literature matching your nucleophile/coupling partner. No standardized dilutions or biological controls apply.

Biological Roles

This product is a small, synthetic nitrohalophenolic building block used in chemical research. It does not have a recognized physiological role.

• General notes (informational, not item-specific claims):
  • Phenolic moieties are common in natural products and can engage in hydrogen bonding and redox chemistry, but heavily deactivated nitrohalophenols like this compound are typically used as synthetic intermediates rather than biological probes.
  • Nitro and halogen substituents modulate lipophilicity and electron density; in medicinal chemistry, such groups are used to tune potency and metabolic stability after further derivatization.

No clinical or therapeutic claims are made. For research/lab use only.

Buffer Applications

Not typically applicable. 4-Chloro-2-fluoro-5-nitrophenol is not used as a buffer component. As a weak acid, its phenolic pKa is influenced by substituents, but it is not part of standard buffering systems. For lab work, choose established buffers (e.g., phosphate, acetate, Tris) appropriate to your pH range and ionic strength.

Green Alternatives

While this product is a solid aryl building block (not a solvent), greener choices can be made in the surrounding process chemistry.

• Greener solvent choices for typical transformations:

  • SNAr: Replace DMF/DMSO where possible with 2-MeTHF, CPME, propylene carbonate, or MeCN, balancing rate vs. ease of removal and safety.
  • Cross-coupling: Use bio-derived 2-MeTHF or green ethers (CPME) in place of dioxane/THF; aqueous micellar media with surfactants (e.g., TPGS-750-M) are viable for some Pd-catalyzed couplings.
  • Workup: Favor EtOAc/IPA/H2O systems over chlorinated solvents for extraction and crystallization.

• Reagent and energy considerations:

  • Bases: Carbonates (K2CO3, Cs2CO3) and organic superbases (DBU) can reduce waste vs. stoichiometric inorganic hydroxides in some SNArs.
  • Catalysis: Modern Pd catalysts at ppm–ppb levels in micelles or flow reactors can reduce metal usage and improve E-factors.
  • Temperature: Intensification via microwaves or flow can shorten times and lower overall energy consumption.

Comparison snapshot (general):

• DMF vs 2-MeTHF: DMF offers superior polarity for SNAr but has health/environmental concerns and difficult removal; 2-MeTHF is bio-based and easy to remove but may require higher temperature/longer time.
• Dioxane vs CPME: Dioxane is problematic (suspected carcinogen); CPME is hydrophobic, forms fewer peroxides than THF, and often enables water-tolerant conditions.

Note: Green choices must be validated for your specific substrate/nucleophile and desired selectivity.

Pharmaceutical Uses

• Item-specific pharmacopeial status or excipient role: Not specified for this item; refer to CoA/Spec Sheet if applicable.

General information (non-clinical):

• This compound is best viewed as a synthetic intermediate/scaffold in discovery chemistry. It may be transformed (e.g., by SNAr, coupling, or nitro reduction) to generate drug-like analogs, but it is not itself an excipient or approved pharmaceutical ingredient.
• For GMP or clinical manufacturing, ensure sourcing with appropriate quality systems, impurity profiles, and residual solvent controls; this SKU is designated for research use only.

Physical Properties

• Item-specific properties from Product Data:

  • Appearance: Not specified for this item; refer to CoA/Spec Sheet.
  • Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
  • Storage conditions: Room temperature (per Product Data).
  • Shipped in: Not specified for this item; refer to CoA/Spec Sheet.

• Literature/general property trends for 4-chloro-2-fluoro-5-nitrophenol (reference only):

  • Molecular formula: C6H3ClFNO3 (literature)
  • Molecular weight: ~191.54 g/mol (literature)
  • Physical state: typically a crystalline solid for closely related nitrohalophenols (literature trend).
  • Acidity: phenolic OH substantially acidified by ortho/para nitro and halogen substituents; pKa is expected to be appreciably lower than phenol (literature expectation), facilitating formation of soluble phenolates in basic media.
  • Solubility profile: limited in water as neutral phenol; increased solubility in polar aprotic organics (DMF, DMSO, NMP, acetone) and in alcohols; significantly more soluble in aqueous base as the phenolate salt (general phenol behavior).
  • Partitioning: electron-deficient phenols are less hydrophobic than parent halobenzenes; logP expected to be moderate (literature expectation for nitrohalophenols), but item-specific value is not available here.

Important: Where specific numerical values (mp, bp, density, refractive index, UV cutoff, trace impurities) are required, consult the item’s CoA/Spec Sheet; they are not specified for this item here.

Quality and Grades

• Item-specific grade/purity: Not specified for this item; refer to CoA/Spec Sheet.

• Guidance on grades (general information for research use chemicals):

  • Research-grade materials are suitable for synthetic chemistry, method development, and structure–activity exploration. Where trace-metal content, low water, or low UV background are critical (e.g., for catalysis or analytical applications), look for specifications such as “anhydrous,” “trace-metal screened,” or “HPLC grade.”
  • Stabilizers: Not applicable/unspecified for this item. Phenolic solids typically do not require stabilizers; however, some nitroaromatics can be light-sensitive—amber packaging is often used as a precaution.
  • Documentation: A Certificate of Analysis (CoA) typically lists identity confirmation (e.g., 1H/13C NMR, HPLC area % or GC purity), residual solvents, and water by KF if applicable. For this SKU C979110, consult the CoA/Spec Sheet for definitive specifications.

• Fit-for-use considerations:

  • For cross-coupling or base-driven SNAr, residual inorganic salts and moisture content can affect outcomes. Dry the solid under vacuum if needed and verify purity by HPLC/LC–MS.
  • If using in photochemical or electrochemical methods, consider additional purity controls (UV/Vis background, conductivity) as required by your protocol.

Reaction and Applications

As a highly activated nitrohalophenol, 4-chloro-2-fluoro-5-nitrophenol is a versatile aryl building block enabling orthogonal functionalization.

• Nucleophilic aromatic substitution (SNAr):

  • The aryl fluoride (para to NO2) is strongly activated toward SNAr by O-, N-, S-, and C-nucleophiles under basic conditions in polar aprotic solvents. The aryl chloride (ortho to NO2) is also activated and can undergo SNAr with harder nucleophiles or at elevated temperatures.
  • Chemoselectivity: F typically reacts faster than Cl in SNAr. Sequential substitution allows stepwise installation of two different nucleophiles.

• O-Functionalization of the phenol:

  • Williamson ether synthesis (alkyl halides or sulfonates) and carbonate/urethane formation (e.g., with chloroformates or isocyanates). Phenol protection as silyl ethers or benzyl ethers enables selective reactions at the halo sites.

• Cross-coupling chemistry:

  • The aryl chloride can participate in Pd-catalyzed Suzuki–Miyaura, Buchwald–Hartwig, or Stille couplings using appropriate ligand sets (e.g., dialkylbiaryl phosphines) and bases. Aryl fluoride is generally inert to Pd-catalyzed cross-coupling but remains available for SNAr.

• Nitro group transformations:

  • Reduction to an aniline unveils 4-chloro-2-fluoro-5-aminophenol, enabling diazotization, Sandmeyer variants, or intramolecular cyclizations (e.g., benzoxazoles/benzoxazines after appropriate derivatization).

• Applications:

  • Preparation of densely substituted anisoles/arylethers, diaryl amines, thioethers, and N/O heteroaryl linkers for medicinal chemistry SAR libraries and functional materials, leveraging the complementary reactivity of F, Cl, NO2, and OH.

Reaction Conditions

General literature guidance for electron-deficient nitrohalophenols (not item-specific specifications):

• SNAr on aryl fluoride (para to NO2):

  • Solvent: DMSO, DMF, NMP, or MeCN.
  • Base: K2CO3, Cs2CO3, NaH, or t-BuOK depending on nucleophile.
  • Temperature: 25–120 °C (room temperature for strong nucleophiles; 80–120 °C for weaker ones).
  • Time: 1–24 h; often accelerated under microwave heating.
  • Notes: F typically leaves more readily than Cl; control order of substitution by temperature and nucleophile strength.

• SNAr on aryl chloride (ortho to NO2):

  • Stronger conditions may be required vs F-site. Typical: DMSO or DMF, Cs2CO3 or t-BuOK, 80–140 °C.

• Pd-catalyzed coupling at aryl chloride:

  • Suzuki–Miyaura (to install aryl/alkenyl): Pd2(dba)3 (0.5–2 mol%) + SPhos/XPhos/RuPhos, K3PO4 or K2CO3, toluene/dioxane/H2O, 60–100 °C.
  • Buchwald–Hartwig amination: Pd(OAc)2 (1–3 mol%) + BrettPhos/AdBrettPhos, NaOtBu or Cs2CO3, t-AmOH/toluene, 60–110 °C.
  • Notes: Protect or deprotonate phenol as needed to avoid O-arylation or catalyst inhibition; use bases compatible with phenols.

• Phenol O-alkylation (Williamson):

  • Base: K2CO3 in acetone/MeCN or NaH in THF/DMF.
  • Temperature: 0–60 °C (alkyl halides, tosylates).

• Nitro reduction:

  • Catalytic hydrogenation (H2, Pd/C) in EtOH/EtOAc at ambient–50 °C; or Fe/AcOH, SnCl2/HCl for chemoselective reductions.

Adjust conditions to substrate/nucleophile scope and scale; confirm by small-scale screening.

Safety and Handling

• Item-specific hazard classification (GHS, pictograms, H-statements): Not specified for this item; refer to the SDS for authoritative information.

• General safety profile (phenolic nitrohalogenated aromatics; informational only):

  • Hazards: Phenols can cause skin and eye irritation and may be harmful if inhaled or absorbed through skin. Nitroaromatics may pose additional toxicity concerns. Avoid dust formation and inhalation.
  • PPE: Use lab coat, safety glasses or chemical splash goggles, and appropriate chemical-resistant gloves (e.g., nitrile). Employ a fume hood for weighing and handling to minimize inhalation exposure.
  • Handling: Avoid contact with strong bases and strong oxidizers when not intended for reaction. For intentional base treatment (to form phenolate), ensure pressure relief and controlled addition due to possible exotherm. Prevent contact with metals that may corrode in the presence of phenolic compounds under basic conditions.
  • Storage: Room temperature as per Product Data. Keep tightly closed in a dry, well-ventilated place. Protect from moisture to prevent caking and unintended salt formation; store away from strong acids/bases and oxidizers.
  • First aid (overview; defer to SDS): If on skin/eyes, rinse with plenty of water for at least 15 minutes and remove contaminated clothing. If inhaled, move to fresh air. If ingested, rinse mouth; do not induce vomiting; seek medical advice.

Always consult the product SDS for definitive hazard, exposure limits, and emergency procedures.

Solvent Selection

This compound is an electron-deficient phenol bearing F, Cl, and NO2. It behaves as a weak acid and is polarizable, favoring polar organic media.

• Miscibility/solubility (literature/general):

  • Good: DMSO, DMF, NMP, DMAc, acetonitrile, acetone, methanol/ethanol, ethyl acetate.
  • Moderate: dichloromethane, THF, dioxane.
  • Poor as neutral phenol in water; readily soluble as phenolate in aqueous base.

• Selection by application:

  • SNAr reactions: polar aprotic solvents (DMSO, DMF, NMP) support anionic nucleophiles and enhance rates; 1,4-dioxane or MeCN are alternatives where removal is prioritized.
  • O-alkylation (Williamson): alcohol or polar aprotic solvents with K2CO3/Na2CO3 or stronger base; phase-transfer variants in biphasic toluene/aqueous base also common.
  • Pd-catalyzed cross-coupling at aryl chloride: toluene, dioxane, THF, or tert-amyl alcohol often used with bulky dialkylbiaryl phosphine ligands; polar cosolvents can aid solubility of bases.

• Practical tips:

  • For analytical prep (HPLC), dissolve first in DMSO or MeOH, then dilute with water/aqueous buffer as needed; ensure pH control to avoid precipitation of the neutral phenol.
  • If base is present, anticipate salt formation (phenolate), which changes solubility and extraction behavior; acidify to pH ~2–3 during workup to recover the neutral phenol.

Note: Choose greener solvents where feasible; see Green Alternatives.

Storage and Reconstitution

• Storage (per Product Data): Store at room temperature.
• Container: Keep tightly sealed in original container; use desiccant if ambient humidity is high. Protect from prolonged light exposure as a precaution for nitroaromatics.
• Inerting: Not required for storage, but recommended during moisture-sensitive reactions.
• Reconstitution: Not applicable—this is a solid organic reagent. For solution preparation, dissolve in a suitable organic solvent (e.g., DMSO, DMF, MeCN, acetone, alcohols). Prepare fresh solutions for sensitive transformations; phenolate solutions should be used promptly.
• Stability considerations: Avoid long-term contact with strong bases or oxidizers. If material cakes due to humidity, gently pulverize under dry atmosphere prior to weighing.
• Shipping: Not specified for this item; refer to CoA/Spec Sheet.

Always follow your institution’s chemical hygiene plan and consult the SDS for full handling and storage guidance.

Structure and Identity

4-Chloro-2-fluoro-5-nitrophenol is a polyfunctional nitrohalophenol featuring three strongly electron-withdrawing substituents on a phenolic core.

• Item-specific identifiers from Product Data:

  • CAS: 98404-02-5
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet. (Catalog lists "64257", which is not a full InChIKey.)
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.

• Research use note: For research use only.

• Literature/computed identifiers and features (for reference):

  • Typical molecular formula (literature): C6H3ClFNO3
  • Typical molecular weight (literature, monoisotopic ≈ 191.54 g/mol)
  • Structural features: phenolic OH at C1; F at C2 (ortho to OH); Cl at C4 (para to OH); NO2 at C5 (meta to OH, ortho to Cl, para to F). The aryl ring is thus highly deactivated toward electrophilic substitution and activated toward nucleophilic aromatic substitution at positions bearing halogens.
  • Stereochemistry: none (achiral, planar aromatic).

• 2D structure (described in words): a benzene ring bearing an OH group, with substituents arranged so that fluorine is adjacent to the hydroxyl, chlorine is opposite the hydroxyl (para), and a nitro group sits adjacent to the chlorine. The remaining two ring positions carry hydrogens.

Notes: All literature values are provided for context only and are not item-specific specifications.

Synthetic Utility

The orthogonal reactivity of F, Cl, NO2, and OH on this arene enables rich, divergence-friendly synthesis.

• Orthogonal handles:

  • Aryl F (para to NO2): highly activated for SNAr—ideal for installing alkoxides, amines, thiolates, or stabilized carbanions.
  • Aryl Cl (ortho to NO2): activated for SNAr but also accessible to Pd-catalyzed cross-coupling (Suzuki–Miyaura, Buchwald–Hartwig) with appropriate ligands.
  • Phenolic OH: convertible to ethers, esters, carbonates, or used for directed metalation after protection.
  • Nitro: reducible to anilines, convertible to nitroso/hydroxylamine intermediates, or leveraged as a temporary activating group for SNAr.

• Strategy examples:

  • Sequence A (SNAr-first): Substitute F with a nucleophile (e.g., morpholine) in DMSO/K2CO3, then couple the aryl chloride via Pd catalysis; finish by reducing NO2 to diversify further.
  • Sequence B (Coupling-first): Pd-couple at Cl to introduce aryl/alkenyl motifs, protect OH, then perform SNAr at F to append polar solubilizers; deprotect as needed.
  • Phenol derivatization: Install a carbonate (e.g., p-nitrophenyl or chloroformate-derived) as a traceless activating group for subsequent intramolecular cyclizations (benzoxazoles/benzoxazines) after nitro reduction.

• Retrosynthetic value:

  • Serves as a convergent node to access 1,2,4,5-substituted phenyl frameworks, enabling rapid SAR matrix generation by varying nucleophiles and coupling partners.

Target Specificity

Not applicable. This SKU is a small-molecule chemical reagent, not a biological targeting reagent (e.g., antibody, enzyme inhibitor with defined biological target claims). No antigen/epitope or species reactivity is associated with this product.