Halauxifen , CAS No.943832-60-8

CAS: 943832-60-8 Cat. No.: H986604 Formula: C₁₃H₉Cl₂FN₂O₃ Molecular Weight: 331.13 EC Number: 879-000-5 PubChem CID: 25181547

Storage

Room temperature

Specifications

Storage

Room temperature

Names and Identifiers

Canonical Smiles

COC1=C(C=CC(=C1F)C2=NC(=C(C(=C2)N)Cl)C(=O)O)Cl

IUPAC Name

4-amino-3-chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)pyridine-2-carboxylic acid

InChIKey

KKLBEFSLWYDQFI-UHFFFAOYSA-N

INCHI

1S/C13H9Cl2FN2O3/c1-21-12-6(14)3-2-5(10(12)16)8-4-7(17)9(15)11(18-8)13(19)20/h2-4H,1H3,(H2,17,18)(H,19,20)

Isomeric SMILES

COC1=C(C=CC(=C1F)C2=NC(=C(C(=C2)N)Cl)C(=O)O)Cl

PubChem CID

25181547

Molecular Weight

331.13

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Class Pyridines and derivatives
      • Subclass Phenylpyridines

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Class: Pyridines and derivatives
• Subclass: Phenylpyridines
• Intermediate Tree Nodes: Not available
• Direct Parent: Phenylpyridines
• Alternative Parents: Pyridinecarboxylic acids Phenoxy compounds Anisoles Methoxybenzenes Alkyl aryl ethers Aminopyridines and derivatives Chlorobenzenes Fluorobenzenes Aryl chlorides Aryl fluorides Vinylogous halides Heteroaromatic compounds Amino acids Carboxylic acids Azacyclic compounds Organic oxides Organochlorides Organofluorides Primary amines Hydrocarbon derivatives
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: 2-phenylpyridine - Pyridine carboxylic acid - Pyridine carboxylic acid or derivatives - Phenol ether - Phenoxy compound - Methoxybenzene - Anisole - Alkyl aryl ether - Chlorobenzene - Aminopyridine - Halobenzene - Fluorobenzene - Monocyclic benzene moiety - Benzenoid - Aryl halide - Aryl fluoride - Aryl chloride - Heteroaromatic compound - Vinylogous halide - Amino acid or derivatives - Amino acid - Azacycle - Carboxylic acid derivative - Carboxylic acid - Ether - Organochloride - Organofluoride - Organonitrogen compound - Organic nitrogen compound - Hydrocarbon derivative - Organohalogen compound - Organic oxide - Amine - Organic oxygen compound - Primary amine - Organooxygen compound - Aromatic heteromonocyclic compound
• Description: This compound belongs to the class of organic compounds known as phenylpyridines. These are polycyclic aromatic compounds containing a benzene ring linked to a pyridine ring through a CC or CN bond.
• 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

Chemical and Physical Properties

• Molecular Weight: 331.120 g/mol
• XLogP3: 3.000
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 3
• Exact Mass: 329.997 Da
• Monoisotopic Mass: 329.997 Da
• Topological Polar Surface Area: 85.400 Ų
• Heavy Atom Count: 21
• Formal Charge: 0
• Complexity: 390.000
• 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 antibody or kit-style application protocols apply to this small molecule.
• General laboratory usage examples (research-only, not item-specific):
  • Analytical stock: dissolve in DMSO at 10–50 mM, vortex and sonicate if needed; dilute to working concentrations with MeCN/H2O for LC–MS injections. Filter through 0.2 µm PTFE.
  • Solubility screening: test DMSO, MeCN, MeOH, and buffered saline (pH 7.4 and pH 9) at 1 mg/mL; evaluate by visual inspection and HPLC area count for stability.
  • Stability check: incubate solutions at ambient and 40 C for 24–72 h; analyze by LC–MS to detect hydrolysis or oxidation. Adjust solvent/pH accordingly.

Biological Roles

• Item-specific biological data: Not specified for this item; refer to CoA/Spec Sheet for any available characterization.
• Literature/general context (for research use only, no agricultural claims):
  • Halauxifen-class molecules are synthetic auxin mimics interacting with plant hormone pathways. In biochemical research, they serve as tools to study auxin receptor complexes, signaling modulation, and transcriptional responses in plant systems.
  • Typical in vitro applications: binding assays with auxin receptors/co-receptors, transcriptomic profiling in plant cells/tissues, and transport/uptake studies using radiolabeled or tagged analogs (when available).
  • Metabolism studies: phase I/II biotransformations (oxidation, conjugation such as glucosylation) can be explored in plant microsomes or whole-tissue incubations to map metabolite profiles (research context).
  • Environmental fate research: sorption, hydrolysis, and photolysis kinetics are characterized in controlled lab systems to inform mechanistic understanding; use appropriate containment and waste management.

Buffer Applications

• This product is a small-molecule research compound rather than a buffering reagent. It is not typically used to set or maintain pH in biochemical assays.
• Practical lab note (general):
  • When preparing aqueous working solutions or dosing solutions, select a buffer compatible with your biological system (e.g., phosphate, HEPES, MOPS). Adjust pH to keep the compound in desired ionization state (acid vs. salt) to balance solubility and permeability.
  • Prepare concentrated stocks in DMSO or MeCN, then dilute into the chosen buffer while maintaining final organic cosolvent below assay tolerance levels.

Green Alternatives

• EHS considerations (general for arylpicolinate solids):

  • The compound itself is a non-volatile solid; environmental impact in the lab is primarily tied to solvent and reagent choices during handling, synthesis, and analysis.

• Greener solvent choices (general guidance):

  • Prefer MeCN or EtOAc over chlorinated solvents when feasible for chromatography and sample prep.
  • For SNAr or couplings, consider 2-MeTHF, CPME, or propylene carbonate as replacements for THF/toluene/DMF where compatible with reactivity and workup.

• Comparison (general; not item-specific):

  | Use case | Conventional | Greener alternative | Trade-offs | |---|---|---|---| | Stock solutions | DMSO | 60–80% EtOH/Water (if solubility allows) | Lower solubility; potential precipitation in cold storage | | Flash chromatography | DCM/MeOH | EtOAc/MeOH or Heptane/EtOAc | Different selectivity; may lengthen runs | | Couplings | DMF/NMP | 2-MeTHF, CPME, Cyrene, propylene carbonate | Base/catalyst compatibility; higher bp complicates workup | | Aqueous work | Acetonitrile | MeOH or IPA (for LC, if MS permits) | MS sensitivity and backpressure considerations |

• Process notes:

  • Minimize halogenated solvent waste; use microscale reactions and concentrate by rotavap with cold traps. Employ solid-phase workups to reduce solvent volumes.
  • Evaluate solvent selection via PMI/E-factor and safety profiles (boiling point, flash point, toxicity) before scale-up.

Pharmaceutical Uses

• This compound is not an excipient or pharmaceutical standard; it is provided strictly for research and analytical use. No pharmacopeial status is indicated.
• Potential laboratory roles (general, non-clinical):
  • Analytical system suitability and calibration for LC–MS method development when studying arylpicolinate chemotypes.
  • Internal reference for evaluating microsomal stability, permeability, or protein binding in discovery workflows (comparative benchmarking only).

Physical Properties

• Item-specific values (specs):
  • Appearance: Not specified for this item; refer to CoA/Spec Sheet.
  • Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.
  • Water/peroxide/metal content, UV cutoff, refractive index: Not specified for this item; refer to CoA/Spec Sheet.
• Literature/general property expectations for arylpicolinate carboxylic acids (for planning only; not item specifications):
  • Physical state: typically a crystalline solid (literature).
  • Solubility: sparingly soluble in water at neutral pH; readily soluble in polar aprotic organic solvents (DMSO, DMF, NMP, acetonitrile, acetone) and in alcohols; solubility increases in basic aqueous media via carboxylate formation (literature).
  • Acid–base: contains one carboxylic acid; apparent pKa for analogous benzoic acids often ~4–5 (literature, scaffold-level guidance). Actual pKa depends on substitution pattern.
  • Partitioning: halogenated aryl ethers with a carboxyl group typically show moderate to high logP in neutral form and lower logD at higher pH due to ionization (literature trend).
  • Thermal behavior: many such solids melt/decompose prior to boiling; exact mp/bp must be taken from the specific CoA/Spec Sheet for this item.
• Practical notes:
  • For analytical stock solutions, DMSO or acetonitrile are commonly used; filtration through 0.2 µm PTFE syringes improves reproducibility (general guidance).

Quality and Grades

• Item-specific grade/purity and stabilizers: Not specified for this item; refer to CoA/Spec Sheet.
• Interpreting grades (general guidance):
  • “Analytical/Reference” or “>98%” grades are commonly used for quantitative analytical work (LC–MS/GC–MS calibration, residue analysis). Lower impurity baselines reduce interference and improve method sensitivity.
  • “Screening/Library” grades typically emphasize identity confirmation with acceptable purity for HTS or SAR screening; trace-level impurity profiling may be limited relative to reference standard grades.
  • Stabilizers: none are typically required for aryl carboxylic acids; esters may occasionally include trace acid scavengers. If a stabilizer is present, it will be disclosed on the CoA.
• What is specific to this item:
  • Storage condition provided: room temperature. Other item-specific quality details (assay method, residual solvents, heavy metals, water content, chromatographic purity) are Not specified for this item; refer to CoA/Spec Sheet.
• Recommendations:
  • For quantitation or regulatory method development, request the latest CoA and, if needed, impurity/identity package (1H/13C NMR, HRMS, LC purity, water, residual solvents).

Reaction and Applications

• Research/application domains (non-agricultural, for laboratory research only):
  • Analytical reference: commonly used as a reference material for developing LC–MS residue/metabolite methods and for stability studies of arylpicolinate scaffolds (literature context).
  • SAR and MOA research: probe compound for auxin receptor/transport studies in plant biology at the biochemical level (no claims on agricultural performance; research-only use).
• Representative chemical transformations on the scaffold (literature/general):
  • Esterification/Amidation: convert the carboxylic acid to methyl/ethyl esters or amides using EDCI/HOBt, DCC, or acid chloride methods; useful for pro-molecule analogs or derivatization.
  • Salt formation: preparation of alkali metal or amine salts to modulate solubility and crystallinity for analytics.
  • SNAr on halogenated pyridines: nucleophilic substitution at activated positions (e.g., –F) with O-, N-, or S-nucleophiles under basic conditions (K2CO3/Cs2CO3, DMF, 60–120 C).
  • Cross-coupling on aryl halides: Suzuki–Miyaura or Buchwald–Hartwig to access analog libraries when a coupling handle is present.
• Practical tips:
  • Drying: for acid forms, dry under high vacuum at ambient–40 C over P2O5 or in a desiccator to constant weight prior to analytical weigh-outs.
  • Purification: reverse-phase prep LC (C18, water/MeCN with 0.1% acid) or flash chromatography (DCM/MeOH or EtOAc/hexanes with 0.1% AcOH to sharpen bands).

Reaction Conditions

• The following are literature/general conditions for transformations relevant to the halauxifen scaffold; they are guidance only and not specific to this item:
• Esterification (acid to methyl/ethyl ester):
  • Conditions: MeOH, catalytic H2SO4 or p-TsOH, reflux 2–6 h; or DCC/DMAP in CH2Cl2 at 0–25 C, 2–12 h.
  • Notes: For sensitive substrates, use Steglich esterification (DCC/DMAP) at low temperature to minimize side reactions.
• Amide coupling:
  • Conditions: HATU (1.1 eq), DIPEA (2 eq), DMF or MeCN, 0–25 C, 1–4 h. Alternatively, EDCI (1.2 eq)/HOBt or HOAt with base, 25 C, 4–16 h.
  • Notes: For heteroaryl acids, pre-activation as acid chloride (SOCl2, catalytic DMF) followed by amination in pyridine or DCM can be effective.
• SNAr on halogenated pyridine ring:
  • Conditions: nucleophile (ROH, RNH2), base (Cs2CO3/K2CO3), DMF/DMSO, 80–120 C, 4–24 h.
  • Notes: Electron-withdrawing groups and ring nitrogen enhance reactivity; monitor by LC–MS.
• Suzuki–Miyaura coupling (if aryl halide present):
  • Conditions: Pd(PPh3)4 (1–3 mol%), base (K2CO3, 2 eq), solvent (2-MeTHF/EtOH/H2O or dioxane/H2O), 60–90 C, 4–16 h.
  • Notes: Protect or mask the acid (as ester or salt) if it inhibits catalysis.
• Analytical preparation:
  • Typical LC mobile phases: H2O/MeCN or H2O/MeOH with 0.05–0.1% formic acid or ammonium formate; UV detection often at 220–260 nm alongside MS.

Safety and Handling

• Item-specific hazard data:
  • GHS classification, signal word, pictograms, and H-statements: Not specified for this item; refer to SDS.
• General safety considerations for halogenated aryl carboxylic acids/esters (literature-based, not a substitute for SDS):
  • Expected hazards: may cause skin/eye irritation and respiratory tract irritation; avoid inhalation of dusts and contact with skin/eyes. Handle in a fume hood.
  • PPE: lab coat, safety glasses or face shield, and appropriate chemical-resistant gloves (e.g., nitrile). Avoid open handling of fine powders; use local exhaust ventilation.
  • Incompatibilities: strong oxidizers; strong bases/acids can promote hydrolysis or salt formation; avoid prolonged contact with reactive metals when using strong bases.
  • Thermal/chemical stability: aryl–O–aryl ethers are generally stable; ester analogs can hydrolyze under strong base/acid; carboxylic acids can form salts with bases.
  • First aid (overview): in case of eye or skin contact, rinse with water for at least 15 minutes; remove contaminated clothing. If inhaled, move to fresh air. If ingested, rinse mouth and seek medical attention. Provide SDS to healthcare providers.
  • Spill/leak: avoid dust generation; collect by HEPA vacuum or damp disposable towels; dispose according to local regulations.
• Always consult the product-specific SDS for authoritative hazard, exposure limits, and disposal instructions.

Solvent Selection

• Polarity and solvation (general for halogenated aryl carboxylic acids/esters):
  • Prefer polar aprotic solvents for stock solutions: DMSO, DMF, NMP, acetonitrile. Alcohols (MeOH, EtOH, i-PrOH) are also suitable; solubility often increases upon mild warming and sonication.
  • Aqueous handling: the free acid form is sparingly water-soluble at neutral pH; dissolve using a small amount of DMSO or MeOH, then dilute into buffered media. Alternatively, prepare soluble salts with mild base (e.g., NaHCO3) if compatible with your application.
• Compatibility:
  • Stable in most organic solvents. Avoid prolonged exposure to strong bases in protic solvents if ester hydrolysis is a concern (for ester analogs). For LC–MS, use H2O/MeCN or H2O/MeOH with 0.1% formic acid or ammonium formate, depending on ionization mode.
• Selection tips:
  • For bioassays: DMSO stocks (10–50 mM) are common; final DMSO typically ≤0.5% v/v in assays (general guidance).
  • For synthetic transformations: use polar aprotic solvents (DMF/DMSO) for SNAr on the heteroaromatic ring; use chlorinated solvents or toluene for coupling steps if needed, with due consideration of EHS.
• Quick comparison (general):
  • DMSO: highest solvency; hygroscopic; strong MS background.
  • MeCN: LC–MS friendly; moderate solvency.
  • MeOH/EtOH: protic; useful for salt formation and transesterification contexts.

Storage and Reconstitution

• Item-specific storage and logistics:
  • Storage Conditions: Room temperature (as provided in Product Data).
  • Shipped In: Not specified for this item; refer to CoA/Spec Sheet.
• General storage guidance for small-molecule solids:
  • Keep tightly closed in original container, protected from light and moisture. Store in a desiccator or cabinet at controlled room temperature. Avoid high humidity to prevent clumping and potential hydration.
  • If subdividing, aliquot into amber glass vials with PTFE-lined caps; label with open date and lot/aliquot IDs.
• Reconstitution (general recommendations; not item-specific):
  • Prepare concentrated stocks in dry DMSO or acetonitrile. Typical stock levels: 10–50 mM. For aqueous applications, dilute into buffer immediately before use to minimize precipitation.
  • For the free acid: dissolve in minimal organic solvent or convert to a salt with a mild base for aqueous work. Filter sterilize (0.2 µm) if sterility is required for cell-based assays.
• Stability monitoring:
  • Periodically verify identity/purity by HPLC or LC–MS after prolonged storage. Avoid repeated heating or prolonged exposure to basic conditions that may promote hydrolysis in ester analogs.
• Research Use Note: For research use only.

Structure and Identity

• Item-specific (from Product Data):
  • Product name: Halauxifen (SKU: H986604)
  • CAS: 943832-60-8
  • CID: 25181547
  • InChIKey: 182429 (as provided)
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular formula: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.
• Literature/General identity notes (not item-specific):
  • Halauxifen is the generic name for an arylpicolinate auxin-mimicking small molecule used widely as a herbicidal active in agrochemical R&D. In literature, it features a halogenated pyridine (picolinate) linked via an aryl–O–aryl ether to a substituted benzoic acid/benzoate framework.
  • Typical functional groups: heteroaromatic nitrogen (pyridine), aryl–O–aryl ether linkage, and a carboxylic acid (or its ester analog in proherbicide forms such as the methyl ester). Halogen substituents (Cl/F) are commonly present on the heteroaromatic ring.
  • 2D structure description (literature): a substituted pyridinyl ring bearing halogens and a carboxylate-derived handle, connected through an ether oxygen to a substituted benzene ring; overall a biaryl ether with one ring heteroaromatic.
• Stereochemistry: No stereocenters are typically present in the canonical halauxifen scaffold (literature).

Synthetic Utility

• Functional group manifold (literature/general for halauxifen scaffold):
  • Carboxylic acid handle: enables esterification (Fischer, Steglich), amidation (EDC/HOBt, HATU), or conversion to acyl chlorides/anhydrides for further derivatization.
  • Aryl–O–aryl ether linkage: generally robust; however, demethylation or ether exchange is feasible under strong conditions for analog generation.
  • Halogenated heteroaromatic (pyridine): supports SNAr, metal–halogen exchange, and palladium-catalyzed cross-couplings at suitably activated positions.
• Retrosynthetic value:
  • Common disconnections include: (1) aryl–O coupling (nucleophilic substitution of a heteroaryl halide by a phenoxide), (2) assembly of the benzoic acid fragment followed by ether formation, and (3) late-stage halogenation on the heteroaryl ring to tune electronics.
• Derivatization strategies:
  • Pro-molecule approach: convert acid to alkyl esters to modulate lipophilicity and controlled hydrolysis in model systems.
  • Bioisosteres: replace carboxylic acid with tetrazole or sulfonamide; adjust heteroaryl substitution to probe receptor interactions in plant biology research.
• Purification/characterization:
  • LC–MS (ESI−/ESI+) depending on ionization of acid/ester; 1H/13C NMR in DMSO-d6 or CDCl3; HRMS for exact mass confirmation.

Target Specificity

• Item-specific biological target data (antigen/epitope/clone/isotype/species) are not applicable to this small-molecule chemical.
• For biochemical research context only (literature): halauxifen-class molecules engage plant auxin-related pathways; no antibody/biologic target information applies here.