N-(3-Chlorophenyl)phthalamic acid , CAS No.5406-21-3

CAS: 5406-21-3 Cat. No.: N1067130 Formula: C₁₄H₁₀ClNO₃ Peso molecolare: 275.680 Numero EC: 666-310-9

Storage

Room temperature

Specifications

Condizioni di conservazione di stoccaggio

Room temperature

Nomi e identificatori

Sorrisi canonici

C1=CC=C(C(=C1)C(=O)NC2=CC(=CC=C2)Cl)C(=O)O

IUPAC Name

2-[(3-chlorophenyl)carbamoyl]benzoic acid

InChIKey

XSSZPZGQMKGAKN-UHFFFAOYSA-N

INCHI

1S/C14H10ClNO3/c15-9-4-3-5-10(8-9)16-13(17)11-6-1-2-7-12(11)14(18)19/h1-8H,(H,16,17)(H,18,19)

Peso molecolare

275.680

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Classe Benzene and substituted derivatives
      • Subclass Anilides
        • Level5 Aromatic anilides
          • Level6 Benzanilides

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Classe: Benzene and substituted derivatives
• Subclass: Anilides
• Intermediate Tree Nodes: Aromatic anilides
• Direct Parent: Benzanilides
• Alternative Parents: Benzoic acids Benzamides Benzoyl derivatives Chlorobenzenes Aryl chlorides Secondary carboxylic acid amides Monocarboxylic acids and derivatives Carboxylic acids Organopnictogen compounds Organooxygen compounds Organonitrogen compounds Organochlorides Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Benzanilide - Benzamide - Benzoic acid or derivatives - Benzoic acid - Benzoyl - Halobenzene - Chlorobenzene - Aryl chloride - Aryl halide - Secondary carboxylic acid amide - Carboxamide group - Carboxylic acid derivative - Carboxylic acid - Monocarboxylic acid or derivatives - Hydrocarbon derivative - Organohalogen compound - Organochloride - Organonitrogen compound - Organopnictogen compound - Organic oxygen compound - Organic nitrogen compound - Organooxygen compound - Organic oxide - Aromatic homomonocyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as benzanilides. These are aromatic compounds containing an anilide group in which the carboxamide group is substituted with a benzene ring. They have the general structure RNC(=O)R', where R,R'= benzene.
• 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: 275.680 g/mol
• XLogP3: 3.300
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 3
• Exact Mass: 275.035 Da
• Monoisotopic Mass: 275.035 Da
• Topological Polar Surface Area: 66.400 Ų
• Heavy Atom Count: 19
• Formal Charge: 0
• Complexity: 348.000
• 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 vendor-tested bioassay or immunoassay application protocols are provided for this small-molecule building block.

• Typical laboratory uses (general):
  • Synthesis: cyclodehydration to the corresponding imide; amide/ester coupling at the carboxyl group; Pd-catalyzed cross-coupling on the 3-chlorophenyl ring.
  • Analytical stock solutions: prepare at 10–100 mM in anhydrous DMSO or DMF; dilute into reaction media or assay buffers as needed.

For step-by-step synthetic procedures, consult peer-reviewed literature for phthalamic acid cyclizations and N-aryl chloride cross-couplings, and adapt to your substrate and equipment.

Biological Roles

This product is intended for research use only. It is not a biological reagent per se, and no biological function is assigned for this catalog item.

• General note (literature context): Aromatic phthalimide/phthalamic motifs occur in a variety of research probes and materials; however, N-(3-chlorophenyl)phthalamic acid itself does not have an established physiological role. Any bioactivity reported for related N-aryl phthalimides or amides is scaffold-dependent and cannot be generalized.
• Chemical biology relevance (conceptual):
  • The carboxylic acid can be used to conjugate to amines (amide formation) or to immobilize on amine-functionalized surfaces, potentially enabling screening libraries or materials with H-bonding arrays.
  • After cyclodehydration to the imide, the rigid, planar imide ring often shows strong π–π interactions, relevant in materials studies rather than cellular pathways.

No claims are made regarding metabolic pathways, targets, or in vivo roles. For any biological experiments, ensure appropriate solubilization (e.g., DMSO stocks diluted into assay buffers) and control for compound aggregation/precipitation. Always comply with institutional biosafety guidance.

Buffer Applications

This compound is not a buffering agent and is not typically used to prepare biological buffers. It contains a carboxylic acid but lacks the conjugate base/acid pair behavior and solubility profile desired for practical buffering in aqueous systems.

• Practical note: If introduced into aqueous buffers for assays, dissolution will generally require a co-solvent (e.g., DMSO) or pH adjustment to form the carboxylate. Validate solubility and avoid precipitation by slow dilution and keeping final organic content within assay limits (commonly ≤1–2% v/v DMSO).

For buffer preparation guidance, refer instead to dedicated buffers such as phosphate, HEPES, MOPS, or acetate systems.

Green Alternatives

While the substance itself is a solid building block rather than a process solvent, greener choices center on reaction media and dehydrating strategies used with it.

• Greener solvent choices (literature/best practice):
  • Prefer 2-methyltetrahydrofuran (2-MeTHF), CPME, or bio-ethanol over chlorinated solvents where feasible for coupling or cyclodehydration workflows. DMF/DMAc/NMP offer performance but carry regulatory concerns; consider propylene carbonate or ethyl acetate where solubility permits.
• Greener dehydrations to the imide:
  • Acetic anhydride (reagent/solvent) is comparatively benign and recyclable vs SOCl2/POCl3. Polyphosphoric acid (PPA) enables solvent-minimized protocols at elevated temperature.
  • Solid-supported carbodiimides (e.g., PS-DCC) or catalytic dehydrations (e.g., acetic anhydride with catalytic acid) can reduce waste.

Comparison (general guidance):

• Option: Acetic anhydride reflux

  • Pros: halogen-free, recyclable, simple workup
  • Cons: Large solvent volumes; acetylation side products if nucleophiles present

• Option: SOCl2-mediated cyclization

  • Pros: Fast at lower temps; high conversions
  • Cons: Corrosive byproducts (SO2, HCl); off-gassing; scrubbing required

• Option: PPA melt (80–120 °C)

  • Pros: Minimal solvent; often high yield
  • Cons: Viscous handling; challenging workup

Adopt DoE to balance solubility, EHS profile, and throughput; validate product quality (CoA-based) after process changes.

Pharmaceutical Uses

No pharmacopeial grade or excipient designation is provided for this item. It is supplied for research use only.

• Formulation/excipient role: Not typical. Aromatic phthalamic acids are generally used as synthetic intermediates rather than as formulation excipients.
• Process chemistry context (literature):
  • Useful as an intermediate toward N-aryl phthalimides, which may appear in medicinal chemistry campaigns as scaffolds, linkers, or protecting groups.
  • The carboxylic acid can be leveraged for pro-drug exploration or conjugation in discovery settings, but such activities are outside the scope of this catalog listing and carry no implied suitability for human/animal use.
• Regulatory: No USP/EP monograph is known for this specific compound. For any GMP-related work, a comprehensive specification set (identity, assay, impurities, residual solvents, elemental impurities) and vendor qualification would be required; none is claimed here.

Use strictly in preclinical laboratory research. Do not use for diagnostic or therapeutic purposes.

Physical Properties

Item-specific specifications are not provided in the Product Data for this SKU. The following are general/literature expectations for N-aryl phthalamic acids of this structure; do not treat as specifications.

• Appearance (item-specific): Not specified for this item; refer to CoA/Spec Sheet.
• Melting point (literature expectation): typically high for phthalamic acids/imides precursors (often >150 °C), but an exact MP for this specific compound is not readily available in standard references.
• Boiling point: Not applicable (decomposes before boiling under ambient pressure for analogous solids; literature trend).
• Density: Not specified for this item; refer to CoA/Spec Sheet.
• Solubility (literature/experience):
  • Water: expected to be very low at neutral pH due to aromaticity; solubility increases in basic aqueous media via carboxylate formation.
  • Organic: soluble in polar aprotic solvents (DMSO, DMF, NMP); sparingly to moderately soluble in alcohols (MeOH/EtOH) upon warming; limited in nonpolar solvents (toluene, hexanes).
• Acid–base behavior (literature):
  • Carboxylic acid pKa for analogous aromatic acids typically ~3–4; amide N is essentially nonbasic (conjugated). Exact pKa values for this compound are not located here.
• LogP (qualitative): expected moderate (aromatic rings + Cl increase lipophilicity; carboxylate reduces under basic conditions). No numeric value provided.
• Refractive index/UV cutoff: Not specified for this item; refer to CoA/Spec Sheet.

For process design, verify all quantitative properties on the lot-specific CoA before use.

Quality and Grades

• Grade/Purity (item-specific): Not specified for this item; refer to CoA/Spec Sheet.
• What this means in practice:
  • Without a stated grade (e.g., “98%,” “AR,” “HPLC”), users should confirm assay, impurity profile, and any stabilizers on the lot-specific CoA before deploying in critical synthesis.
  • For solid building blocks like aryl phthalamic acids, relevant quality attributes typically include: organic purity (HPLC/GC/NMR), residual solvents, water content (KF), halide identity/level (to confirm meta-chloro substitution), and assay by qNMR if applicable.
• UV background and chromatography:
  • If intended for photochemical or trace analysis work, verify UV absorbance profile; aryl systems often have significant UV absorption. If “HPLC grade” were required, this would imply low UV-absorbing impurities and low fluorescence background—no such claim is made here.
• Stabilizers/Additives: Not specified for this item; refer to CoA/Spec Sheet.
• Documentation best practices:
  • Request CoA, NMR spectrum, HPLC trace, MS, and optionally elemental analysis to confirm C/H/N/Cl stoichiometry (literature formula C14H10ClNO3) and assess inorganic residue.
  • If you plan telescoped cyclodehydrations to the imide, ensure low inorganic salts and carbodiimide residues (if any) to avoid side reactions.

Storage note (item-specific): Room temperature per Product Data. Protect from moisture for reproducibility in coupling/dehydration chemistry.

Reaction and Applications

This compound is a versatile intermediate linking a phthalamic acid core to a meta-chloro aniline moiety. Key application families (literature/practice):

• Cyclodehydration to N-(3-chlorophenyl)phthalimide:
  • Dehydrating agents such as acetic anhydride (reflux), SOCl2 (with a catalytic base), POCl3, P2O5, or polyphosphoric acid convert phthalamic acids to the corresponding imides in good yields.
  • Practical note: remove water continuously (Dean–Stark) if using azeotropic solvents; monitor by TLC/LC–MS (loss of CO2H and shift in polarity).
• Functionalization of the 3-chlorophenyl ring:
  • The aryl chloride can participate in Pd-catalyzed cross-couplings (Suzuki–Miyaura, Buchwald–Hartwig, Stille) or nucleophilic aromatic substitutions (if activated by additional substituents), enabling rapid access to N-aryl phthalimides or amides with tailored substituents.
  • Metal–halogen exchange (e.g., with t-BuLi at low temp) can install directing groups; quench with electrophiles to diversify the N-aryl fragment (expert handling required).
• Carboxylate chemistry at the acid terminus:
  • Coupling to form esters or secondary amides using EDC/HOBt, DIC/DMAP, or HATU/DIPEA in DMF/DCM; the adjacent amide can influence reactivity (intramolecular H-bonding).
  • Salt formation (Na/K) provides water-soluble derivatives useful for crystallization or purification.
• Supramolecular/solid-state uses:
  • The acid–amide motif offers robust H-bonding networks; literature reports use similar phthalamic acids in crystal engineering and co-crystal formation studies.

These applications make N-(3-chlorophenyl)phthalamic acid a practical precursor to imides and a platform for diversification on the N-aryl ring.

Reaction Conditions

General literature guidance for transformations of N-aryl phthalamic acids; optimize per substrate and scale. Values are indicative, not specifications.

• Cyclodehydration to imide:
  • Acetic anhydride (Ac2O): Reflux 1–4 h, 3–6 equiv relative to substrate; can act as solvent. Workup by quench into ice–water and neutralization; typical isolated yields reported for analogous substrates: 70–95%.
  • SOCl2 (with catalytic DMF): 2–5 equiv SOCl2, 0.05–0.1 equiv DMF, reflux 1–3 h; inert atmosphere recommended. Remove volatiles, then neutralize to precipitate product.
  • PPA: 80–120 °C, 1–3 h; viscous medium—dilute with ice–water, neutralize, and filter.
• Amide/ester formation at the acid group:
  • HATU/DIPEA (DMF, 0–25 °C to RT, 2–12 h). Monitor by HPLC; base equivalents 2–3. For hindered alcohols, add catalytic DMAP and elevate to 40–60 °C.
  • Acid chloride route: Oxalyl chloride (1.5–2.0 equiv) with catalytic DMF in DCM, 0 °C to RT, 1–2 h, then couple with nucleophile and base at 0–25 °C.
• Cross-coupling on the 3-chlorophenyl ring (after or before cyclization):
  • Suzuki–Miyaura: Pd(PPh3)4 (2–5 mol%), base (K2CO3/Cs2CO3), 1,4-dioxane/H2O (3:1), 80–100 °C, 6–16 h.
  • Buchwald–Hartwig amination: Pd2(dba)3 (1–2 mol%) + bulky biaryl phosphine (2–6 mol%), NaOtBu, toluene or dioxane, 90–110 °C, 8–20 h.
• Analytical monitoring: TLC often shows modest movement; LC–MS preferable. Expect mass consistent with literature MW ~275.69 g/mol; imide shows –18 amu (loss of H2O) relative to acid/amide pair.

Always run small-scale trials and ensure compatibility with the compound’s acid/amide functionalities.

Safety and Handling

• GHS classification and pictograms (item-specific): Not specified for this item; refer to SDS.
• Likely hazards (general for aromatic carboxylic acids and aryl amides):
  • May cause skin/eye irritation and respiratory tract irritation as dust. Avoid inhalation of particulates and contact with eyes/skin.
  • Not expected to form peroxides. Not volatile; main risks are from dust and thermal decomposition products.
• PPE (good laboratory practice):
  • Safety glasses or goggles; lab coat; appropriate chemically resistant gloves (e.g., nitrile). Use a particulate respirator if dust generation is likely and ventilation is inadequate.
• Handling guidance:
  • Work in a fume hood to control dust. Prevent electrostatic accumulation when weighing.
  • Avoid strong heating; decomposition may produce corrosive/irritating fumes (HCl, NOx, CO/CO2) typical for chlorinated aromatics and amides.
• Incompatibilities (general):
  • Strong oxidizing agents; strong bases/acids for prolonged periods (hydrolysis possible under forcing conditions); dehydrating agents will cyclize it to the imide.
  • Acid chlorides/carbodiimides may react at the carboxyl group; handle mixtures deliberately.
• First aid (overview; defer to SDS):
  • Inhalation: move to fresh air; seek medical attention if symptoms persist.
  • Skin/eyes: rinse with water for several minutes; remove contaminated clothing; seek medical attention if irritation continues.
  • Ingestion: rinse mouth; do not induce vomiting; seek medical advice.
• Fire fighting (general):
  • Use CO2, dry chemical, or foam. Combustion can release HCl and NOx; wear SCBA.

Always consult the SDS for authoritative hazard classification and response procedures.

Solvent Selection

As a polar, multifunctional aromatic solid (carboxylic acid + secondary aryl amide), N-(3-chlorophenyl)phthalamic acid dissolves best in hydrogen-bonding or polar aprotic media.

• Polarity/miscibility profile (general/literature):
  • Preferred: DMSO, DMF, DMAc, NMP (good solubility at ambient; excellent on mild heating).
  • Useful: Methanol, ethanol, isopropanol (often require heating/sonication); acetone/MeCN show variable solubility.
  • Limited: Ethyl acetate, chlorinated solvents (DCM/CHCl3) may suspend; solubility improves with small amounts of base (e.g., Et3N) forming carboxylate salts.
  • Poor: Nonpolar hydrocarbons (hexanes, heptane) and ethers at RT.
• pH-assisted dissolution:
  • Aqueous basic media (NaHCO3/Na2CO3) can form the carboxylate, giving high aqueous solubility; acidify to reprecipitate.
  • Avoid prolonged strong base if preserving the amide; harsh conditions can hydrolyze.
• Choosing among solvents (practical tips):
  • For cyclodehydration to the imide, use acetic anhydride (solvent/reagent), toluene or xylene with Dean–Stark (with catalysts like Ac2O, PPA), or SOCl2-mediated conditions (solventless or in refluxing toluene).
  • For amide couplings at the carboxyl group, DMF or DCM (with coupling reagents) are standard; include base (DIPEA) as needed.
• Small comparison (literature/experience):
  • DMSO vs DMF: DMSO maximizes solubility for analytical stocks; DMF preferred for many coupling reactions due to lower viscosity and easier workup.
  • Alcohols: greener but may compete in dehydrations/esterifications; control water content.

Verify solvent compatibility with downstream steps and analytical methods.

Storage and Reconstitution

• Storage (item-specific): Room temperature (per Product Data). Keep container tightly closed in a dry, well-ventilated place. Protect from moisture to maintain assay and prevent variable solubility.
• Shipped in: Not specified for this item; refer to CoA/Spec Sheet.
• Stability (general): Aromatic carboxamides are typically stable for extended periods at ambient conditions when dry and protected from light. Avoid prolonged exposure to strong acids/bases.
• Reconstitution/preparation of solutions (practical guidance):
  • Analytical stocks: Dissolve in anhydrous DMSO or DMF to 10–100 mM. Vortex/sonicate gently if needed. Filter (PTFE, 0.2 µm) for HPLC/assay use.
  • Aqueous work: To introduce into aqueous systems, prepare a DMSO concentrate and dilute slowly into buffer under stirring; final DMSO ≤1–2% v/v is common. Alternatively, adjust pH with mild base to form the carboxylate salt transiently.
  • Reaction charges: For cyclodehydration, charge neat acetic anhydride or selected solvent prior to heating; ensure venting/scrubbing if using SOCl2.
• Freeze–thaw: Not applicable for solids. If preparing frozen aliquots of DMSO solutions, minimize freeze–thaw cycles by aliquoting; store at ≤–20 °C in dry conditions and equilibrate to RT before opening.

Always refer to the product’s CoA and SDS for lot-specific stability, compatibility, and handling details. Research use only.

Structure and Identity

N-(3-Chlorophenyl)phthalamic acid is an N-aryl phthalamic acid bearing a meta-chloro substituent on the aniline-derived ring. It contains a benzene ring ortho-disubstituted by a carboxylic acid and an amide carbonyl (the phthalamic acid core), with the amide nitrogen further substituted by a 3-chlorophenyl group.

• Item-specific registry data (from Product Data):

  • CAS: 5406-21-3
  • CID: 221873
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.

• Structure description (general/literature-based):

  • Core motif: ortho-benzamide–benzoic acid (phthalamic acid) featuring adjacent amide (–CONH–) and carboxylic acid (–CO2H) on the same benzene ring (1,2-relationship).
  • N-substituent: 3-chlorophenyl group attached to the amide nitrogen (N–H retained; secondary amide). The chloro is meta to the N–C bond on the aniline ring.
  • Functional groups: aromatic carboxylic acid, secondary aryl amide, aryl chloride; multiple H-bond donor/acceptor sites.
  • Stereochemistry: achiral; no stereocenters.

• Empirical formula and mass (literature/computed for this structure):

  • Molecular formula (literature): C14H10ClNO3
  • Molecular weight (literature): ~275.69 g/mol

Note: The descriptive and formula information above is provided as literature-based structural context. For the definitive identifiers supplied with this specific catalog item (e.g., SMILES, InChIKey), please consult the CoA/Spec Sheet.

Synthetic Utility

N-(3-Chlorophenyl)phthalamic acid offers orthogonal handles—an aryl chloride, a carboxylic acid, and a conjugated secondary amide—enabling diverse transformations (literature/practice):

• Cyclodehydration → N-(3-chlorophenyl)phthalimide:
  • Robust route to a rigid imide ring. The imide can undergo further N–aryl ring diversification (cross-coupling) or serve as a protecting/anchoring motif.
• Carboxyl activation and coupling:
  • Convert the acid to the acid chloride (SOCl2, oxalyl chloride) or use coupling reagents (EDC/HCl with HOBt/HOAt, DIC/DMAP, HATU/DIPEA) to form esters or amides. The neighboring amide may H-bond intramolecularly, sometimes slowing acylation—use catalysts (DMAP) and maintain anhydrous conditions.
• Aryl chloride diversification:
  • Pd-catalyzed Suzuki–Miyaura coupling with boronic acids (bases: K2CO3, Cs2CO3; solvents: dioxane/H2O, toluene) to append aryl/heteroaryl groups.
  • Buchwald–Hartwig amination to install amines (ligands: XPhos/BrettPhos; catalysts: Pd2(dba)3 or Pd(OAc)2; bases: NaOtBu, Cs2CO3).
  • Negishi/Stille couplings or directed ortho-metalation strategies for advanced elaboration (handle with care due to amide acidity).
• Hydrolysis/Transamidation (forcing):
  • Under strong acidic or basic conditions and heat, N-aryl amides can hydrolyze; this delivers phthalic acid derivatives and 3-chloroaniline—typically slow due to resonance stabilization.
• Supramolecular assembly/co-crystal formation:
  • The acid–amide synthon forms reliable H-bonding motifs for crystal engineering and cocrystal screens.

These features make the compound a practical node in retrosynthetic planning for imide-containing architectures and N-aryl elaborations.

Target Specificity

Not applicable. This product is a small-molecule chemical building block, not a biological targeting reagent (e.g., antibody, ligand with defined biomolecular target). No antigen/epitope, species reactivity, clone, or isotype information applies.