2-(4-Chlorophenyl)isonicotinic acid - ≥97% , CAS No.500586-44-7

CAS: 500586-44-7 Cat. No.: C1339227 Formula: C₁₂H₈ClNO₂ Peso molecolare: 233.65 PubChem CID: 284943

GRADE & PURITY ≥97%

Storage

Room temperature

Shipped In

Normal

Specifications

Specifiche e purezza

≥97%

Condizioni di conservazione di stoccaggio

Room temperature

Spedito in

Normal

Purezza

≥97%

Nomi e identificatori

• Sorrisi canonici: C1=CC(=CC=C1C2=NC=CC(=C2)C(=O)O)Cl
• IUPAC Name: 2-(4-chlorophenyl)pyridine-4-carboxylic acid
• InChIKey: BRBHDPCWBZWZTP-UHFFFAOYSA-N
• INCHI: 1S/C12H8ClNO2/c13-10-3-1-8(2-4-10)11-7-9(12(15)16)5-6-14-11/h1-7H,(H,15,16)
• Isomeri SMILES: C1=CC(=CC=C1C2=NC=CC(=C2)C(=O)O)Cl
• PubChem CID: 284943
• Peso molecolare: 233.65

Taxonomic Classification

Taxonomy Tree

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

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Classe: Pyridines and derivatives
• Subclass: Phenylpyridines
• Intermediate Tree Nodes: Not available
• Direct Parent: Phenylpyridines
• Alternative Parents: Pyridinecarboxylic acids Chlorobenzenes Aryl chlorides Heteroaromatic compounds Monocarboxylic acids and derivatives Carboxylic acids Azacyclic compounds Organopnictogen compounds Organooxygen compounds Organonitrogen compounds Organochlorides Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: 2-phenylpyridine - Pyridine carboxylic acid or derivatives - Pyridine carboxylic acid - Halobenzene - Chlorobenzene - Benzenoid - Monocyclic benzene moiety - Aryl halide - Aryl chloride - Heteroaromatic compound - Azacycle - Monocarboxylic acid or derivatives - Carboxylic acid - Carboxylic acid derivative - Organic nitrogen compound - Organic oxygen compound - Organopnictogen compound - Organic oxide - Hydrocarbon derivative - Organooxygen compound - Organonitrogen compound - Organochloride - Organohalogen compound - Aromatic heteromonocyclic compound
• Descrizione: 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

Proprietà chimiche e fisiche

• Peso molecolare: 233.650 g/mol
• XLogP3: 3.000
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 2
• Exact Mass: 233.024 Da
• Monoisotopic Mass: 233.024 Da
• Topological Polar Surface Area: 50.200 Ų
• Heavy Atom Count: 16
• Formal Charge: 0
• Complexity: 251.000
• 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

Not applicable as a biological reagent. No tested immunoassay or cell-based application protocols are provided for this small molecule.

• For synthetic use, consider:

  • Preparing 100–500 mM stock solutions in dry DMSO or DMF for parallel synthesis or HTS assay development (chemistry context only).
  • Filtration through 0.2 µm PTFE syringe filters before automated dispensing to remove particulates.

• Item-specific recommended dilutions/conditions: Not specified for this item; refer to CoA/Spec Sheet for any available internal test methods.

Biological Roles

This product is a synthetic aromatic carboxylic acid intended for research chemistry. No biological role is assigned for this specific derivative.

• General context (non-clinical, literature):

  • Pyridine-4‑carboxylic acid (isonicotinic acid) motifs are common heteroaromatic fragments in chemical biology probes and medicinal chemistry scaffolds; they can engage in hydrogen bonding (carboxylate/amide) and metal coordination (pyridyl N).
  • The para‑chloro phenyl group modulates lipophilicity and electronics, affecting binding in SAR exploration. The chlorine can serve as a synthetic handle for diversification rather than as a bioactive feature per se.

• Cautions:

  • Do not infer pharmacological or clinical properties from this information. This product is provided strictly for research use only as stated in the Product Data.

Buffer Applications

Not typically used as a buffer. Although it contains a carboxylic acid and a basic pyridine nitrogen, this compound is not employed as a standard buffering agent.

• Practical note:
  • For aqueous workups, conversion to the carboxylate (e.g., NaHCO3/Na2CO3) improves water solubility, but this is for extraction/purification rather than buffering.
  • Use dedicated buffers (e.g., phosphate, acetate, HEPES) for pH control in biological or analytical applications.

Green Alternatives

While the compound itself is a solid building block, greener choices can be made in the processes that use it (solvents, reagents, energy input).

• Greener solvent options (literature guidance):

  • Replace DMF/DMAc with Cyrene, propylene carbonate, N‑butyl pyrrolidone, or sulfolane where compatible.
  • Use 2‑MeTHF, CPME, or EtOAc instead of dioxane/toluene for esterifications and some couplings.
  • Employ aqueous micellar media (e.g., TPGS‑750‑M) for amide couplings or Suzuki reactions when substrates permit.

• Coupling reagent choices:

  • Prefer catalytic amide formations (C–O activation/ester intermediates) or greener reagents like T3P over DCC/HOBt (reduced hazardous byproducts).

• Energy and waste:

  • Flow chemistry and microwave heating can reduce reaction times and energy consumption.
  • Design crystallization-driven purifications to minimize chromatography and solvent waste.

• Example comparison (general): | Workflow | Conventional | Greener alternative | Trade-offs | |---|---|---|---| | Amide coupling | DMF + HATU | 2‑MeTHF + T3P | Solubility may require cosolvent; T3P byproducts are water-soluble | | Suzuki on Ar–Cl | Dioxane/toluene | CPME/H2O or EtOH/H2O | Catalyst/ligand re-optimization often needed | | Esterification | DCM + DCC/DMAP | EtOAc + catalytic acid | Longer times; higher temp but easier workup |

Note: Validate solvent/catalyst compatibility for this specific substrate before scale-up.

Pharmaceutical Uses

No pharmacopeial or excipient status is provided for this item; it is sold for research use only.

• Typical role in drug discovery (general):

  • Employed as a heteroaryl building block to prepare amide/ester libraries (isonicotinamide derivatives) and to explore cross-coupling diversification via the para‑chloro phenyl group.
  • Useful for tuning physicochemical properties (pKa shifts, lipophilicity) during lead optimization.

• Formulation context:

  • If used as an analytical reference or synthetic intermediate, stocks are commonly prepared in DMSO or DMF due to limited aqueous solubility of the neutral acid.

• Compliance note:

  • No medical, diagnostic, or therapeutic use is implied. Confirm internal quality requirements with the CoA before use in regulated workflows.

Physical Properties

Note: No item-specific physical specifications are provided. Values below are literature-based expectations for closely related structures and should be used only as general guidance.

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight: ~233.65 g/mol (literature/computed for C12H8ClNO2)
• Acid/base character (literature): weak carboxylic acid (pKa for pyridine-4‑carboxylic acids typically ~4.6–5.0); pyridine N is weakly basic (conjugate acid pKaH typically ~5.2). Exact values for this substituted derivative are not widely reported.
• Solubility profile (literature/typical behavior)
  • Water: low at neutral pH; increased solubility as its carboxylate salt (basic aqueous media)
  • Organic: soluble in polar aprotic solvents (DMSO, DMF, NMP), moderately soluble in MeOH/EtOH; sparing in nonpolar media
• Partitioning (literature expectation): aromatic biaryl with one acid group and one halogen; logP expected in the low-to-moderate range in its neutral form; becomes highly water soluble upon deprotonation.
• Melting/boiling points: Not widely reported for this exact compound; analogous aryl‑isonicotinic acids often melt in the 180–260 °C range with decomposition. Not specified for this item; refer to CoA/Spec Sheet.
• Refractive index, density, UV cutoff, metal limits, residuals: Not specified for this item; refer to CoA/Spec Sheet.

Quality and Grades

• Grade/purity: Not specified for this item; refer to CoA/Spec Sheet.

• Intended use: Research use only (per Product Data). Not for human or veterinary applications.

• What “research grade” typically implies:

  • Suitable for synthetic organic chemistry, medicinal chemistry hit-to-lead work, and analytical characterization.
  • Trace metal content, residual solvent levels, and chromatographic purity are not standardized across vendors; verify by CoA for your lot if these attributes are critical.

• Impurities to consider for this structural class (general guidance):

  • Residual starting materials (e.g., corresponding biaryls, unchlorinated/over‑chlorinated analogs)
  • Esters or anhydrides (if acid activation was used), residual coupling reagents
  • Inorganic salts from workup

• Stabilizers/additives:

  • None stated. If long-term storage is planned for moisture‑sensitive downstream derivatizations (e.g., acid chloride formation), keep the solid tightly closed and dry.

• Recommended verification (best practice):

  • 1H/13C NMR in DMSO‑d6 or CDCl3 with a base drop to sharpen carboxylic signal; HRMS to confirm C12H8ClNO2; HPLC or UPLC purity check with diode‑array detection around 200–350 nm.

Reaction and Applications

This compound is a versatile heteroaryl building block combining a carboxylic acid handle, a pyridine nitrogen, and a para‑chloro aryl coupling site.

• Representative transformations (literature/general):

  • Amide coupling: Convert to isonicotinamide derivatives using EDC/HOBt, HATU/DIPEA, or T3P; acid chloride route via SOCl2/oxalyl chloride then amination.
  • Esterification: Fischer esterification (ROH/H+, Dean–Stark) or Steglich esterification (DCC/DMAP) to modulate lipophilicity and solubility.
  • Cross-coupling at the para‑chloro phenyl: Suzuki–Miyaura (B(pin)/B(OH)2 partners), Buchwald–Hartwig amination, or Negishi/Kumada, leveraging modern Pd/Ni catalysts and bulky ligands optimized for aryl chlorides.
  • Decarboxylative functionalization: Activation as redox-active esters (e.g., NHPI) enabling Ni/photoredox decarboxylative cross-couplings to access 2‑(4‑chlorophenyl)‑substituted pyridyl radicals/alkylations.
  • N‑oxidation/coordination: Pyridine N-oxidation (mCPBA) as a directing group; coordination to transition metals for catalysis or material assembly.

• Application areas (non-clinical):

  • Medicinal chemistry: generation of diverse isonicotinamide/ester libraries with a 2‑(4‑chlorophenyl) motif.
  • Materials/coordination: ligand precursors where the carboxylate and pyridyl N chelate metal centers.

• Practical tips:

  • Ensure anhydrous conditions for acid chloride formation; trap HCl with base.
  • For aryl chloride couplings, use electron-rich bulky ligands (e.g., XPhos, SPhos, BrettPhos) and higher temperatures (90–120 °C) as needed.
  • Carboxylate salts can improve solubility in polar solvents and facilitate phase-transfer in biphasic couplings.

Reaction Conditions

General, literature-based conditions for common transformations of this substrate (optimize per system; not item-specific specs):

• Amide coupling (carboxyl → amide):

  • HATU (1.1–1.5 eq), DIPEA (2–4 eq), DMF or NMP, 0–25 °C to rt, 1–16 h; typical isolated yields 70–95% for unhindered amines.
  • EDC·HCl (1.2 eq), HOAt/HOBt (0.1–0.2 eq), DIPEA (2–3 eq), DCM/DMF, 0 °C→rt.
  • T3P (50% in EtOAc, 1.3–1.8 eq) with amine (1.1–1.5 eq) in 2‑MeTHF or EtOAc, 25–60 °C.

• Esterification:

  • Steglich: DCC (1.1 eq), catalytic DMAP (5–10 mol%), DCM or EtOAc, 0 °C→rt.
  • Fischer: ROH (excess), catalytic H2SO4 or p‑TsOH, reflux (Dean–Stark for higher alcohols).

• Aryl chloride cross-coupling (para‑Cl on phenyl):

  • Suzuki–Miyaura: Pd(dppf)Cl2 (2–5 mol%), K3PO4 or K2CO3 (2–3 eq), dioxane/H2O or CPME/H2O, 80–110 °C, 4–16 h.
  • Buchwald–Hartwig amination: Pd2(dba)3 (1–2 mol% Pd) + XPhos/BrettPhos (2–4 mol%), NaOtBu or Cs2CO3, toluene/DMAc, 90–120 °C.

• Decarboxylative cross-coupling (via RAEs, literature):

  • Activate to NHPI ester (DIC/DMAP), then NiCl2(dppp) (5–10 mol%) + photocatalyst (e.g., Ir(ppy)3, 1 mol%), blue LEDs, MeCN, rt.

• Workup/purification tips:

  • Acid/base partitions: extract carboxylate into aqueous base; re-acidify to precipitate.
  • Crystallization from alcohols or EtOAc/hexanes often effective for neutral acid or esters.

Safety and Handling

Safety classifications are not provided in the Product Data; consult the SDS for authoritative guidance. The notes below reflect general good laboratory practice for aromatic carboxylic acids and aryl chlorides.

• GHS information (item-specific):

  • Signal word: Not specified for this item; refer to SDS.
  • Hazard statements / pictograms / classification: Not specified for this item; refer to SDS.

• Anticipated hazards (general):

  • May cause skin/eye irritation; dust may irritate respiratory tract. Avoid inhalation of powders and contact with eyes/skin.
  • Not expected to form peroxides. Nonvolatile solid; combustible organic.

• Handling and PPE (best practice):

  • Work in a fume hood; minimize dust generation.
  • Wear lab coat, safety glasses, and appropriate gloves (e.g., nitrile). Use respiratory protection if powders become airborne and ventilation is inadequate.

• Incompatibilities (general):

  • Strong bases (will form carboxylate salts; exotherm possible upon neutralization)
  • Strong oxidizers (as with most organics)
  • Strong electrophiles (acid chlorides formed intentionally require moisture exclusion)

• First aid (summary; defer to SDS):

  • Skin/eye contact: Rinse with water for several minutes; remove contaminated clothing; seek medical attention if irritation persists.
  • Inhalation: Move to fresh air; seek medical advice if symptoms occur.
  • Ingestion: Rinse mouth; do not induce vomiting; obtain medical attention.

• Fire fighting: Use CO2, dry powder, or foam; avoid water streams that may spread material. Thermal decomposition may release HCl/NOx.

Solvent Selection

As a moderately polar, heteroaromatic carboxylic acid, this solid typically dissolves best in polar aprotic media or alcohols, and in basic aqueous systems as its carboxylate.

• Polarity/miscibility (general expectations):

  • Preferred: DMSO, DMF, NMP for stock solutions and coupling reactions
  • Also useful: MeOH/EtOH (especially with gentle warming or base), acetonitrile for some catalytic couplings
  • Limited solubility: Toluene, EtOAc at ambient; improved upon heating or as salts/esters
  • Water: low as the neutral acid; good as carboxylate in basic buffers

• Choosing solvents by task:

  • Amide/ester formation: DMF, DCM, or MeCN (with carbodiimide or uronium reagents); 2‑MeTHF or EtOAc for greener workflows
  • Cross-coupling on the aryl chloride: toluene, dioxane, CPME, or DMAc with Pd/Ni catalysts; include aqueous base if Suzuki
  • Salt formation and purification: aqueous NaHCO3/Na2CO3 extractions; recrystallization from alcohols or alcohol/ester mixtures

• Small comparison (general):

  • DMSO vs DMF: DMSO offers broader solubility and thermal stability; DMF is lower viscosity and easier to remove.
  • MeCN vs DCM: MeCN is polar protic-compatible and higher bp; DCM is highly volatile and less green.

Storage and Reconstitution

• Storage (item-specific): Room temperature (Product Data). Keep tightly closed in a dry place; protect from prolonged exposure to moisture and light.

• Shipping (item-specific): Shipped under normal ambient conditions (Product Data).

• Shelf life and stability:

  • Aromatic carboxylic acids are generally stable solids under ambient conditions. Avoid strong bases/acids and high humidity to prevent salt formation or hydrolysis of derived esters/acid chlorides.

• Reconstitution and stock solutions (general guidance):

  • Prepare concentrated stocks in anhydrous DMSO or DMF (e.g., 100–500 mM) for synthetic or analytical use.
  • For aqueous operations, dissolve with a small amount of base (e.g., NaOH) to form the carboxylate, then adjust pH as needed.
  • Filter sterilize solutions if required for instrumentation (0.2 µm PTFE/NYLON depending on solvent).

• Freeze–thaw/aliquoting:

  • Solid: no freeze–thaw concerns.
  • Solutions: store in sealed amber vials at 2–8 °C (or frozen for DMSO) and minimize freeze–thaw cycles by aliquoting.

• Disposal: Follow institutional and local regulations for halogenated organic waste; neutralize acids/bases appropriately before disposal.

Structure and Identity

A biaryl, pyridinecarboxylic‑acid building block featuring a para‑chlorophenyl substituent at the 2‑position of an isonicotinic acid scaffold.

• Item-specific identifiers (from Product Data)

  • CAS: 500586-44-7
  • SKU: C1339227
  • Storage: Room temperature (Product Data)
  • Shipped: Normal (ambient) (Product Data)
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet. (Product Data lists a nonstandard string)
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.

• Computed/literature structural details (non-spec, for reference)

  • Preferred name: 2-(4-Chlorophenyl)isonicotinic acid (isoquinoline is not involved; “isonicotinic” = pyridine‑4‑carboxylic acid core)
  • Molecular formula (derived from structure): C12H8ClNO2 (literature/computed)
  • Molecular weight: ~233.65 g/mol using 35.45 for Cl (literature/computed)
  • Core features: biaryl system (pyridine–phenyl), carboxylic acid at pyridine C4, para‑chloro on the phenyl ring, one ring nitrogen (pyridine).
  • 2D description: a pyridine ring bearing a carboxyl group at the ring para position relative to N (isonicotinic acid), and a 4‑chlorophenyl substituent at the pyridine 2‑position.

• Functional groups and handles

  • Carboxylic acid (for amidation/esterification, coupling chemistry)
  • Aryl chloride (para‑Cl) as a potential cross‑coupling site (Pd/Ni catalysis)
  • Heteroaromatic nitrogen (pyridine) for coordination or N‑oxide formation.

Synthetic Utility

Key handles make this substrate valuable in multi-dimensional diversification campaigns.

• Carboxylic acid (at pyridine C4):

  • Amide formation with primary/secondary amines (EDC/HOBt, HATU, PyBOP, T3P). Offers rapid access to isonicotinamide derivatives, a prominent motif in medicinal chemistry.
  • Ester formation for pro-moieties or protecting groups; subsequent hydrolysis provides a traceless handle for solubility control.
  • Activation to acid chlorides or anhydrides for higher reactivity.

• Aryl chloride (para on phenyl):

  • Cross-coupling platform: Suzuki–Miyaura (boronates), Buchwald–Hartwig (amines), Ullmann-type (under Cu catalysis), and Chan–Lam (with boronic acids/amines under oxidative conditions).
  • Late-stage diversification orthogonal to carboxyl derivatization, enabling 2D SAR matrices (vary amide while coupling at Ar–Cl).

• Pyridine nitrogen:

  • Coordination to metals (catalyst ligation; MOF/coordination polymer precursors) and N‑oxidation as a directing group for C–H functionalization on adjacent positions.

• Retrosynthetic value:

  • Serves as a convergent node for biaryl assembly (preinstalled 4‑chloro phenyl) plus downstream amide/ester elaboration, reducing step count in scaffold hopping campaigns.

Target Specificity

Not applicable. This product is a small-molecule reagent and does not have antibody/biomolecular target specificity attributes.

• Antigen/epitope/clone/isotype: Not applicable.
• Species reactivity: Not applicable.