3-(2-Methylphenyl)picolinic acid - ≥96% , CAS No.1226205-60-2

CAS: 1226205-60-2 Cat. No.: M963467 Formula: C₁₃H₁₁NO₂ Peso molecolare: 213.23 PubChem CID: 52983872

GRADE & PURITY ≥96%

Storage

Room temperature

Specifications

Specifiche e purezza

≥96%

Condizioni di conservazione di stoccaggio

Room temperature

Purezza

≥96%

Nomi e identificatori

Sorrisi canonici

CC1=CC=CC=C1C2=C(N=CC=C2)C(=O)O

IUPAC Name

3-(2-methylphenyl)pyridine-2-carboxylic acid

InChIKey

LVVPVMDWQNWONK-UHFFFAOYSA-N

INCHI

1S/C13H11NO2/c1-9-5-2-3-6-10(9)11-7-4-8-14-12(11)13(15)16/h2-8H,1H3,(H,15,16)

Isomeri SMILES

CC1=CC=CC=C1C2=C(N=CC=C2)C(=O)O

PubChem CID

52983872

Peso molecolare

213.23

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 Toluenes Heteroaromatic compounds Carboxylic acids Azacyclic compounds Organopnictogen compounds Organooxygen compounds Organonitrogen compounds Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: 3-phenylpyridine - Pyridine carboxylic acid - Pyridine carboxylic acid or derivatives - Toluene - Monocyclic benzene moiety - Benzenoid - Heteroaromatic compound - Carboxylic acid derivative - Carboxylic acid - Azacycle - Organic nitrogen compound - Hydrocarbon derivative - Organic oxide - Organooxygen compound - Organonitrogen compound - Organopnictogen compound - Organic oxygen 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: 213.230 g/mol
• XLogP3: 2.700
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 2
• Exact Mass: 213.079 Da
• Monoisotopic Mass: 213.079 Da
• Topological Polar Surface Area: 50.200 Ų
• Heavy Atom Count: 16
• Formal Charge: 0
• Complexity: 254.000
• 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 assay-specific protocols are provided for this small-molecule reagent.

• General usage examples (research context)
  • Stock preparation: dissolve the solid in anhydrous DMSO (e.g., 10–50 mg/mL); sonicate gently if needed. Filter (0.22 µm PTFE) before use in assays.
  • Amide synthesis: activate acid (e.g., HATU/DIPEA in DMF), add amine at 0–5 °C, warm to RT, and monitor by LC-MS.
  • Complex preparation: basify to pH ~7.5–8.0 in H2O/MeOH, add metal salt slowly with stirring, and monitor by UV–vis or MS.

For validated, application-specific protocols, consult primary literature relevant to picolinic acid derivatives.

Biological Roles

• Product Data: Research Use Only.

• Literature/general context (no clinical claims)

  • Picolinic acid itself is a known chelating metabolite; however, 3-(2-methylphenyl)picolinic acid is a synthetic derivative without established endogenous biological role.
  • As an aromatic carboxylic acid bearing a pyridyl nitrogen, it can form picolinate complexes with transition metals. Such complexes are often studied for catalysis, photophysics, and as model systems for metalloenzyme mimicry.
  • The carboxylate acidity and pyridyl basicity provide pH-dependent ionization, influencing membrane permeability and binding to protein metal sites in biophysical studies.
  • In medicinal chemistry workflows, picolinic-acid–like motifs can serve as metal-binding fragments or as directing groups in late-stage diversification (purely research/discovery context).

No specific biochemical pathway participation or receptor/target interactions are established for this exact compound in the literature provided here.

Buffer Applications

This compound is not a conventional buffering agent. While it contains an acidic (carboxyl) and a basic (pyridyl) site, it is not typically used to prepare laboratory buffers.

• Practical note
  • For aqueous handling, pH adjustment can convert the acid to its carboxylate salt to improve solubility, but standard buffers (e.g., phosphate, HEPES, acetate) are recommended for controlled pH systems.
  • If metal chelation is undesired in biochemical assays, avoid using this compound in buffered systems containing trace metals.

Green Alternatives

Greener choices relate primarily to solvent and coupling reagent selection rather than the substrate.

• Preferred solvents (relative greenness vs common choices)

  • 2-MeTHF vs THF: similar polarity with better renewability and lower peroxide tendency.
  • CPME vs DCM/Et2O: broader liquid range, low peroxide formation, and favorable phase separations.
  • EtOAc or Me-THF for extraction instead of chlorinated solvents when feasible.

• Coupling chemistry

  • Use COMU/TCDI/CDI or green peptide-coupling protocols to reduce HOBt-related hazards and minimize urea waste.
  • Enzymatic or catalytic esterifications in green solvents (2-MeTHF, Cyrene) can replace classical Fischer conditions.

• Small comparison (general)

  | Task | Conventional | Greener alternative | Trade-offs | | --- | --- | --- | --- | | Amide coupling | DCM/DMF + HATU | 2-MeTHF/EtOAc + CDI/COMU | Solubility may limit loading | | Workup | DCM extraction | EtOAc/MTBE | Slightly higher solvent volume | | Drying | Molecular sieves | Vacuum + azeotrope | Time vs convenience |

Note: Selection must balance EHS metrics with reaction performance; verify with small-scale trials.

Pharmaceutical Uses

No pharmacopeial excipient status or formulation role is specified for this item.

• General discovery context (non-clinical)

  • Utilized as a heteroaromatic building block in medicinal chemistry SAR campaigns to introduce a picolinic acid handle for metal binding or as a convertible directing group.
  • Potential roles include: intermediate for amide-linked libraries, prodrug ester precursors, or ligand fragments for metalloenzyme-targeted tool compounds—strictly for research and development.

• Compliance note

  • For any GMP or clinical use, dedicated qualification, impurity profiling, and regulatory documentation would be required. This product is sold strictly for research use only.

Physical Properties

• Product Data (item-specific)

  • 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.

• Literature/Computed values (reference only; not item specifications)

  • Expected physical state: crystalline solid (typical for aromatic carboxylic acids).
  • Estimated MW (from name-derived formula C13H11NO2): ~214.23 g/mol (literature estimate).
  • Acidic functionality: one carboxylic acid (typical pKa for picolinic/benzoic acids ~3–5; electron-withdrawing pyridyl may modestly acidify; literature guidance only).
  • Basic site: pyridyl nitrogen (conjugate acid pKa typically ~1–5 for pyridines; literature guidance only).
  • Solubility (qualitative, literature): low in water at neutral pH; soluble in polar aprotic solvents (DMSO, DMF, NMP); improved aqueous solubility upon basification (carboxylate salt) or in alcohols with heating.
  • Partitioning: biaryl scaffold suggests moderate hydrophobicity (logP likely >2; literature expectation).

• Practical notes (general)

  • For NMR, DMSO‑d6 or CD3OD commonly dissolve aromatic acids; basification (e.g., NaOD/D2O) can aid aqueous spectra.
  • Refractive index, UV cutoff, residual water/peroxide/metal levels: Not specified for this item; refer to CoA/Spec Sheet.

Quality and Grades

• Product Data (item-specific)

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

• Interpreting common grades (general guidance)

  • Research grade: suitable for most synthetic and discovery workflows; impurity profiles may include trace solvents or isomeric byproducts.

  • 98% or >99% purity (if specified): supports structure–activity studies and metal complexation; check residual solvent and water content if critical.

  • HPLC-grade designation (for solvents) or LC/MS suitability (for solids) implies low UV background and low non-volatile residue; for building blocks like this acid, look for tight limits on related biaryl isomers and residual halides/metals from coupling steps.

• Stabilizers/additives

  • No stabilizer is expected for this class; if present, it will be disclosed on the CoA. Verify any salt forms (e.g., sodium carboxylate) vs free acid.

• Recommendations

  • Request CoA for exact assay, identity confirmation (1H/13C NMR, HRMS), residual metal content (if cross-coupling was used), water (Karl Fischer), and chromatographic purity method.
  • For metal-critical catalysis, ask for ICP-MS data (Pd, Ni, Cu). For crystallography/complexation, verify absence of coordinating impurities (amines, pyridines).

Reaction and Applications

As a picolinic-acid–derived biaryl, this compound functions both as a building block and as a ligand precursor.

• Building block transformations (literature/general)

  • Amide formation: carbodiimide (EDC/HOBt), uronium (HATU/HBTU), or CDI protocols; pyridyl N can modestly affect reactivity—use base (DIPEA, NMM) and control stoichiometry.
  • Esterification: Fischer (ROH/H+, reflux) or Steglich (DCC/DMAP, RT) to access esters for protection or solubility tuning.
  • Decarboxylative couplings: access biaryl/alkenyl derivatives via Ag/Cu/Ni/Pd-catalyzed decarboxylative cross-coupling (literature precedent for pyridine-2-carboxylates).
  • Directed C–H functionalization: the N,O bidentate motif (picolinamide derivatives) is a classic directing group for ortho-C–H activation; conversion to the amide enables diverse C–C/C–X formation.

• Coordination chemistry

  • Picolinate ligation: deprotonated acid (picolinate) chelates metals (e.g., Zn2+, Cu2+, Ln3+) through pyridyl N and carboxylate O. The o-tolyl substituent adds steric/electronic modulation for catalyst design or luminescent complexes.

• Practical tips

  • Drying: if anhydrous conditions are needed, azeotrope with toluene or dry under high vacuum at mild temperature; avoid decarboxylation by excessive heat.
  • Activation: for acid chloride formation, oxalyl chloride or thionyl chloride with catalytic DMF; exclude moisture and quench cautiously.
  • Purification: strong π–π interactions can cause tailing; add 0.1–1% acetic acid or triethylamine to silica eluents depending on free acid vs ester/amide form.

Reaction Conditions

Illustrative conditions (literature-style guidance; adapt to your substrate and scale):

• Amide coupling (carboxylic acid → amide)

  • HATU (1.1 eq), DIPEA (2 eq), DMF or NMP, 0.05 M, 0–25 °C, 1–4 h; typical isolated yields 70–95% with unhindered amines. For greener variant, CDI (1.2 eq) in 2-MeTHF, 25–50 °C.

• Esterification (Fischer)

  • ROH (5–10 eq), catalytic H2SO4 or p-TsOH, Dean–Stark (if water immiscible) or neat/alcohol reflux, 2–16 h; 60–90% yields common. Steglich: DCC (1.1 eq), DMAP (0.1 eq), DCM, 0–25 °C.

• Acid chloride formation

  • Oxalyl chloride (1.5–2 eq), catalytic DMF, DCM, 0 °C → RT, 1–3 h; follow by in situ coupling with amine in DCM/THF and base (Et3N).

• Decarboxylative cross-coupling (carboxylate as coupling handle)

  • Ni/Pd catalysis with redox-active esters (NHPI derivatives): DMA or MeCN, 25–60 °C, 4–16 h; use Zn/Mn as reductant in some protocols.

• Metal complexation (picolinate formation)

  • Adjust pH 6–8 to deprotonate CO2H; mix with metal salts (e.g., Zn(OAc)2) in MeOH/H2O; room temperature assembly delivers N,O-chelated complexes.

These ranges are general references from heteroaromatic carboxylic acid chemistry; optimize stoichiometry, temperature, and time for your specific substrate and scale.

Safety and Handling

• Product Data (item-specific)

  • GHS Classification: Not specified for this item; refer to SDS.
  • Signal Word: Not specified for this item; refer to SDS.
  • H-Statements/Pictograms: Not specified for this item; refer to SDS.

• General laboratory safety guidance for aromatic carboxylic acids and pyridines (not a substitute for SDS)

  • Likely hazards: may cause skin/eye irritation and respiratory tract irritation as dust. Avoid inhalation and contact with skin/eyes.
  • PPE: lab coat, safety glasses or chemical splash goggles, and appropriate chemical-resistant gloves (e.g., nitrile). Handle solids in a fume hood to avoid dust exposure.
  • First aid (general): rinse eyes cautiously with water for several minutes; wash skin with soap and water; move exposed persons to fresh air; seek medical attention if symptoms persist.
  • Storage incompatibilities: avoid strong oxidizers and strong bases/acids that may cause salt formation or degradation; avoid acylation reagents unless intended. Keep container tightly closed to limit moisture uptake and contamination.
  • Thermal behavior: decompose on strong heating; avoid grinding-generated heat and ignition sources of organic dusts.
  • Waste: dispose according to institutional and regulatory guidelines for organic acids/heteroaromatics. Do not release to the environment.

Always consult the product’s SDS for authoritative hazard, toxicological, and handling information.

Solvent Selection

This compound is a biaryl heteroaromatic carboxylic acid. Solvent choice is driven by ionization state and target operation (reaction vs. analysis).

• Polarity/miscibility profile (literature-based expectations)

  • Poorly soluble in water at neutral pH; readily forms soluble carboxylate salts in basic aqueous media.
  • Good solubility in polar aprotics (DMSO, DMF, NMP) and moderate in hot alcohols (MeOH, EtOH, iPrOH). Limited in nonpolar hydrocarbons unless converted to esters/salts.

• Typical selections by task

  • Reaction medium: DMF, DCM, THF, dioxane, MeCN for coupling/activation; toluene or xylene for high-temperature steps; 2-MeTHF as greener ether option.
  • Workup: partition with EtOAc/MTBE; basify aqueous layer to extract anions or acidify to precipitate the free acid.
  • Analytical: dissolve in MeOH/ACN with 0.1% acid/base as needed; DMSO stocks (10–50 mg/mL) for bioassay sample prep.

• Comparative notes

  • DMSO vs DMF: DMSO excels for stock solutions and stability; DMF suits amidations but may react with acid chlorides.
  • Alcohols: facilitate Fischer esterification; risk of transesterification in subsequent steps.

Item-specific solvent limits and UV cutoffs: Not specified for this item; refer to CoA/Spec Sheet.

Storage and Reconstitution

• Product Data (item-specific)

  • Storage Conditions: Room temperature.
  • Shipped In: Not specified for this item; refer to CoA/Spec Sheet.

• General storage guidance

  • Keep tightly closed in the original container, protected from moisture and direct light. Store in a dry place; inclusion of a desiccant is recommended for long-term stability.
  • Avoid prolonged exposure to elevated temperatures. For multi-month storage, a cool, dry cabinet is preferred.

• Reconstitution and solutions

  • Prepare concentrated stocks in dry DMSO, DMF, or MeOH. Typical laboratory stocks: 10–50 mg/mL. For aqueous use, dissolve under basic conditions to form the carboxylate salt, then adjust pH as needed.
  • Filter solutions through 0.22 µm PTFE prior to sensitive applications. Divide into single-use aliquots to minimize freeze–thaw; store DMSO stocks at −20 °C when compatible with your workflow.

• Stability notes

  • Avoid strong acids/bases in solution for extended periods to prevent hydrolysis or decarboxylation. Monitor solution stability by LC/MS over time.

Refer to the product CoA and SDS for any item-specific stability data and handling instructions.

Structure and Identity

Brief overview: 3-(2-Methylphenyl)picolinic acid is a heteroaromatic carboxylic acid featuring a pyridine-2-carboxylic acid (picolinic acid) core bearing an o-tolyl (2-methylphenyl) substituent at the 3-position. The scaffold offers a bidentate N,O donor set (pyridyl N and carboxylate O), useful in coordination chemistry and as a directing group in synthesis.

• Product Data
  • CAS: 1226205-60-2
  • InChIKey: 210529 (as provided; appears non-standard/truncated—verify against CoA/Spec Sheet)
  • 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/Computed (for reference only; not item specifications)
  • Putative molecular formula (from structure name): C13H11NO2 (neutral acid) or C13H11NO2; common MW estimate ≈ 213–215 g/mol depending on exact isotopic composition.
  • Structural features: one pyridine ring; one benzenoid ring with ortho-methyl; one carboxylic acid at pyridine C2; aryl–aryl linkage at pyridine C3.
  • 2D description in words: a six-membered pyridine ring bearing a carboxylic acid ortho to the ring nitrogen (picolinic motif); at the carbon next to the acid (pyridine C3) an o-tolyl ring is attached, the tolyl ring carrying a methyl group adjacent to the biaryl junction.
• Stereochemistry: none (achiral, no stereocenters).

Synthetic Utility

Key functional motifs and reactivity (general literature guidance):

• Carboxylic acid handle

  • Amide/ester formation enables rapid derivatization; conversion to acid chloride or mixed anhydrides expands options (Friedel–Crafts acylations of activated aromatics, Curtius rearrangement via acyl azide to reach amines/isocyanates).
  • Decarboxylation pathways under radical or metal catalysis enable C–C bond formations (e.g., Minisci-type on heteroarenes using derived N-oxides/esters).

• Pyridyl nitrogen

  • Acts as a Lewis base, enabling temporary coordination to catalysts (Pd, Ni, Ru) that can accelerate cross-couplings or C–H activations when transformed to picolinamides (bidentate directing groups).

• Biaryl core with ortho-methyl

  • Provides steric bias for atroposelective or regioselective transformations; oxidation of benzylic methyl can furnish aldehyde/acids, enabling further diversification.

• Retrosynthetic value

  • The scaffold can arise from biaryl coupling (e.g., Suzuki/Migita) followed by oxidation to the acid or, conversely, coupling of a preformed picolinic acid derivative with an o-tolyl partner.

• Purification and analytics

  • Expect strong UV absorbance (pyridine/phenyl). LC-MS-friendly; monitor amide/ester derivatives by ESI+/- depending on ionization state.

Target Specificity

Not applicable. This product is a small-molecule heteroaromatic acid, not an antibody, enzyme, or biologic. No target/epitope/isotype information applies. For molecular recognition or binding studies, refer instead to the Synthetic Utility and Reaction & Applications sections.