2-Chloro-4-fluoro-benzenepropionic acid - ≥98% , CAS No.174603-38-4

CAS: 174603-38-4 Cat. No.: C299488 Formula: C₉H₈ClFO₂ Molecular Weight: 202.61

GRADE & PURITY ≥98%

Synonyms

DTXSID10472158 | 3-(2-CHLORO-4-FLUORO-PHENYL)-PROPIONIC ACID | CWLAMJYAQMNGPA-UHFFFAOYSA-N | A811667 | AMY16158 | F9994-0613 | Benzenepropanoic acid, 2-chloro-4-fluoro- | F14499 | 2-Chloro-4-fluoro-benzenepropionic acid, AldrichCPR | SCHEMBL5045620 | 3-(2

Storage

Room temperature

Shipped In

Normal

Specifications

Synonyms

DTXSID10472158 | 3-(2-CHLORO-4-FLUORO-PHENYL)-PROPIONIC ACID | CWLAMJYAQMNGPA-UHFFFAOYSA-N | A811667 | AMY16158 | F9994-0613 | Benzenepropanoic acid, 2-chloro-4-fluoro- | F14499 | 2-Chloro-4-fluoro-benzenepropionic acid, AldrichCPR | SCHEMBL5045620 | 3-(2

Specifications & Purity

≥98%

Storage

Room temperature

Shipped In

Normal

Purity

≥98%

Names and Identifiers

Canonical Smiles

C1=CC(=C(C=C1F)Cl)CCC(=O)O

IUPAC Name

3-(2-chloro-4-fluorophenyl)propanoic acid

InChIKey

CWLAMJYAQMNGPA-UHFFFAOYSA-N

INCHI

1S/C9H8ClFO2/c10-8-5-7(11)3-1-6(8)2-4-9(12)13/h1,3,5H,2,4H2,(H,12,13)

Isomeric SMILES

C1=CC(=C(C=C1F)Cl)CCC(=O)O

Molecular Weight

202.61

Reaxy-Rn

9258345

Reaxys-RN_link_address

https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=9258345&ln=

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Phenylpropanoids and polyketides
    • Class Phenylpropanoic acids

• Kingdom: Organic compounds
• Superclass: Phenylpropanoids and polyketides
• Class: Phenylpropanoic acids
• Subclass: Not available
• Intermediate Tree Nodes: Not available
• Direct Parent: Phenylpropanoic acids
• Alternative Parents: Fluorobenzenes Chlorobenzenes Aryl fluorides Aryl chlorides Monocarboxylic acids and derivatives Carboxylic acids Organofluorides Organochlorides Organic oxides Hydrocarbon derivatives Carbonyl compounds
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: 3-phenylpropanoic-acid - Chlorobenzene - Halobenzene - Fluorobenzene - Aryl chloride - Aryl fluoride - Aryl halide - Benzenoid - Monocyclic benzene moiety - Carboxylic acid derivative - Carboxylic acid - Monocarboxylic acid or derivatives - Organic oxygen compound - Organohalogen compound - Organochloride - Organofluoride - Carbonyl group - Organooxygen compound - Hydrocarbon derivative - Organic oxide - Aromatic homomonocyclic compound
• Description: This compound belongs to the class of organic compounds known as phenylpropanoic acids. These are compounds with a structure containing a benzene ring conjugated to a propanoic acid.
• 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: 202.610 g/mol
• XLogP3: 2.400
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 3
• Exact Mass: 202.02 Da
• Monoisotopic Mass: 202.02 Da
• Topological Polar Surface Area: 37.300 Ų
• Heavy Atom Count: 13
• 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

Not applicable as standardized bioassay protocols (e.g., WB, IHC, IF, FC) do not pertain to this small-molecule reagent.

• Practical lab usage (general)
  • For stock solutions, dissolve at 10–100 mM in dry DMSO or DMF; for reaction charging, weigh solid accurately and add directly or via solvent slurry.
  • For workup, consider basify–extract–acidify to isolate the free acid efficiently. Dry organic layers over MgSO4/Na2SO4 and minimize heating to avoid byproduct formation.

Refer to your internal SOPs for reaction setup, inert atmosphere handling, and purification.

Biological Roles

• Item-specific biological information: Not specified for this item; this product is supplied for research use only.

• General context (chemistry/biochemistry)

  • 2-Chloro-4-fluoro-benzenepropionic acid is a small halogenated aromatic carboxylic acid used primarily as a synthetic intermediate. It has no known endogenous biological role.
  • Halogenated arylpropionic motifs appear in medicinal chemistry as lipophilic fragments influencing metabolic stability, membrane permeability, and target binding through halogen bonding and hydrophobic contacts (general SAR principles). However, any biological activity is scaffold- and substituent-dependent and cannot be inferred for this compound alone.
  • The carboxylic acid can form salts with biogenic amines and may be masked as esters or amides to modulate physicochemical properties during probe/API synthesis (prodrug strategies in general medicinal chemistry literature).

No clinical or therapeutic claims are made or implied; this compound is intended strictly as a chemical building block.

Buffer Applications

This compound is not a standard buffering agent.

• Applicability
  • As a monocarboxylic acid (pKa typical of arylpropionic acids ~4–5, literature), it is not commonly used to prepare laboratory buffers with defined pH ranges.
  • If pH manipulation is required during workup, transient formation of its carboxylate (with NaHCO3/Na2CO3) can aid extraction, but this is not a buffering application per se.

For true buffer systems at acidic pH, use established agents such as acetate (pH ~3.6–5.6) or citrate (pH ~3–6.2).

Green Alternatives

• Solvent choices (greener replacements)

  • Replace DMF/DMAc with 2‑MeTHF, CPME, EtOAc, or propylene carbonate when feasible (e.g., Steglich esterifications in EtOAc; Suzuki couplings in 2‑MeTHF or CPME with aqueous base).
  • Use ethanol/2‑propanol for Fischer esterifications instead of halogenated solvents.

• Reagent choices

  • Amide couplings: Favor T3P (in EtOAc/2‑MeTHF) or DIC + Oxyma/ethyl cyano(hydroxyimino)acetate over HATU/HBTU to reduce hazardous waste (literature guidance). Enzymatic esterifications in green solvents are possible for select substrates.
  • Acid activation: CDI (forms CO2/imidazole byproducts) as an alternative to SOCl2/oxalyl chloride when compatible.

• Energy and workup

  • Employ micellar catalysis (TPGS-750-M) for some couplings to reduce organic solvent volumes.
  • Use aqueous bicarbonate washes and crystallization from EtOAc/hexanes or EtOAc/heptane to minimize chlorinated solvent usage.

• Tradeoffs

  • Greener solvents may lower substrate solubility; adjust concentration/temperature or add co-solvents.
  • Some green coupling systems can require longer reaction times or higher catalyst loadings; balance EHS benefits against throughput.

• Quick comparison (general)

  • DMF: high solubility, difficult removal, reproductive hazard; 2‑MeTHF/CPME: renewable/safer, good for Pd couplings, easier workup; EtOAc: biodegradable, great for extraction and crystallization.

Pharmaceutical Uses

• Item-specific regulatory/compendial status: Not specified for this item; no pharmacopeial designation provided.

• General formulation/manufacturing context (no therapeutic claims)

  • Role: Halogenated arylpropionic acids are common intermediates in the synthesis of drug candidates, enabling modular installation of amides, esters, and further aryl substitutions via cross-coupling.
  • Use in route design: The orthogonal aryl chloride versus aryl fluoride reactivity allows late-stage diversification while maintaining a para‑F tag for analytical tracking (19F NMR) or SAR.
  • Excipient status: Not typically used as an excipient.

Any use in GMP manufacturing would require full specification, impurity profiling, and compliance with relevant regulatory guidance; this listing is for research use only.

Physical Properties

• Item-specific specifications (this lot)

  • Boiling point, melting point, density, refractive index, water/peroxide/metal content: Not specified for this item; refer to CoA/Spec Sheet.

• Literature/computed properties (informational; typical for structure class)

  • Physical state: Expected crystalline solid or low-melting solid for arylalkyl carboxylic acids with two ring halogens (literature/general trend).
  • Acid strength (pKa): Carboxylic acid pKa typically ~4.2–4.7 for arylpropionic acids; ring halogens can slightly increase acidity (literature, analogous compounds).
  • Solubility profile (qualitative):
    • Water: Low to very low at neutral pH; increased solubility in basic aqueous media via carboxylate formation (general behavior of aromatic acids).
    • Organic: Good solubility in polar aprotic solvents (DMF, DMSO, NMP); moderate in esters (EtOAc), ketones (MEK, acetone), chlorinated solvents (DCM, CHCl3); lower in nonpolar hydrocarbons (hexanes, heptane) (literature/experience).
  • Partitioning: cLogP predicted in the ~3 range owing to aryl and halo substituents counterbalanced by –CO2H (computational estimate; tool-dependent).
  • Thermal behavior: Carboxylic acids can show broad melting due to polymorphism and hydrogen bonding; decarboxylation not expected under mild heating (general behavior).

Note: Use these literature/computed insights for planning only; verify with item CoA/SDS for process-critical specifications.

Quality & Grades

• Item-specific quality information

  • Grade/purity: Not specified for this item; refer to CoA/Spec Sheet for assay, residual solvents, and impurity profile.
  • Appearance: Not specified for this item; refer to CoA for lot-specific description.

• Guidance on grades (general)

  • Research-grade building blocks are typically assayed by 1H NMR/13C NMR and HPLC/GC for purity; water content by Karl Fischer as applicable. For chromatography-sensitive work, low-UV-absorbance solvents/reagents are preferred, but this solid reagent’s UV properties are generally non-critical.
  • Stabilizers: None typically required for this class; the compound is usually bench-stable. If present, stabilizers/inhibitors would be disclosed on the CoA and may need removal prior to certain reactions (e.g., crystallization, chromatography).
  • Trace metals/ionic impurities: Relevant when used in cross-coupling screens. If ppm limits matter, request CoA/Spec Sheet.

• Recommendations

  • For process development or analytical reference standards, request a detailed CoA including assay basis, residual solvents, and impurity IDs. For medicinal chemistry, confirm identity by NMR and LC–MS upon receipt.

Reaction & Applications

This multifunctional building block combines a reactive carboxylic acid with orthogonally addressable aryl C–Cl and C–F bonds.

• Carboxylic acid derivatizations

  • Amide formation: HATU/HBTU/T3P/DIC–Oxyma or EDCI in DMF/DCM with DIPEA/Et3N; useful for library synthesis of amides bearing the 2‑Cl,4‑F aryl motif.
  • Esterification: Fischer (ROH, catalytic H2SO4), Steglich (DCC/DMAP) for base-sensitive partners; CDI-mediated formation of imidazolides.
  • Acid chloride: SOCl2 or (COCl)2 with catalytic DMF; enables acylations or Curtius rearrangement (via acyl azide) to isocyanates/amines.
  • Redox-active esters (RAEs): N‑hydroxyphthalimide (NHPI) ester formation allows decarboxylative cross-couplings (borylation, arylation, alkylation) under Ni/photoredox catalysis (literature).

• Aryl halide chemistry

  • Pd-catalyzed cross-coupling at C–Cl (Suzuki–Miyaura, Buchwald–Hartwig, Heck). The aryl fluoride typically remains intact, enabling selective mono-functionalization; activation of C–F generally requires special conditions or strongly activating substituents.
  • Lithiation/metal–halogen exchange at C–Cl (e.g., iPrMgCl•LiCl, t‑BuLi at low temperature) with subsequent electrophile trapping; carboxylic acid should be protected/converted to a non-acidic derivative (e.g., Weinreb amide) to avoid acid–base quench.

• Strategy and selectivity

  • Orthogonal handles permit sequential synthesis: first, amide/ester formation at the acid; second, Pd-catalyzed coupling at aryl chloride; optionally, late-stage C–F activation (SNAr rarely viable without additional ring activation).

• Use cases (examples from literature/general practice)

  • Synthesis of fluorinated/halogenated arylalkyl amides and esters for SAR studies.
  • Installation of boron (via Miyaura borylation at C–Cl) to access 4‑fluoro‑2‑substituted boronates for iterative couplings.

Reaction Conditions

The following are literature/general conditions for this functional class; adjust to substrate and scale. They are guidance, not item specifications.

• Amide coupling (carboxylic acid)

  • HATU (1.1–1.5 eq), amine (1.1–1.5 eq), DIPEA (2–4 eq), DMF or DCM, 0–25°C, 1–16 h. Typical isolated yields 70–95% for unhindered partners (literature).
  • T3P (50 wt% in EtOAc), amine, DIPEA, EtOAc/2‑MeTHF, rt to 50°C, 2–6 h; efficient workup via aqueous basification.

• Esterification

  • Fischer: ROH (5–10 eq), catalytic H2SO4 or p‑TsOH, reflux 4–16 h; remove water (Dean–Stark for non-protic cosolvents) to drive conversion.
  • Steglich: DCC (1.2 eq), catalytic DMAP, CH2Cl2, 0°C → rt, 2–12 h; filter urea byproduct.

• Acid chloride formation

  • SOCl2 (2–5 eq), catalytic DMF, reflux 1–3 h; evaporate volatiles under reduced pressure; use immediately or store cold/dry if stable.

• Suzuki–Miyaura at aryl chloride (selective vs C–F)

  • Pd2(dba)3 (1–2 mol%), XPhos/SPhos (2–4 mol%), K3PO4 or Cs2CO3 (2–3 eq), toluene/2‑MeTHF/H2O (biphasic), 80–110°C, 2–12 h. Typical yields 60–90% depending on boronate.

• Buchwald–Hartwig amination

  • Pd(OAc)2 (1–3 mol%), BrettPhos or RuPhos ligand (2–6 mol%), NaOtBu or Cs2CO3, toluene/dioxane, 80–110°C, 6–24 h.

• Redox-active ester (NHP) formation and decarboxylative coupling

  • DIC (1.1 eq), NHPI (1.1 eq), DMAP (cat.), CH2Cl2, rt, 2–4 h → Ni-catalyzed borylation (NiCl2•dppp, B2pin2, base), or photoredox arylation under Ir/Ru catalysts (literature protocols).

Note: Protect or transform the acid (e.g., ester/amide) when employing strong bases or organometallics to avoid acid–base quenching.

Safety & Handling

• Item-specific hazard data

  • GHS classification, pictograms, signal word, and H-statements: Not specified for this item; consult the product SDS for authoritative safety information.

• General safety considerations for aryl carboxylic acids (literature/general)

  • Hazards: May cause skin/eye irritation and respiratory irritation if dusts or aerosols are generated. Avoid ingestion and prolonged contact.
  • PPE: Safety glasses with side shields, lab coat, and appropriate chemical-resistant gloves (e.g., nitrile). Use in a fume hood to avoid inhalation of dust/vapors.
  • First aid (overview):
    • Inhalation: Move to fresh air; seek medical advice if symptoms persist.
    • Skin contact: Wash with soap and water; remove contaminated clothing.
    • Eye contact: Rinse cautiously with water for several minutes; remove contact lenses if present and easy; seek medical attention for persistent irritation.
    • Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.
  • Incompatibilities: Strong oxidizing agents; strong bases/acids may react (neutralization/heat). Convert to salts only with controlled neutralization. Avoid reagents forming acid chlorides (e.g., SOCl2, oxalyl chloride) unless intended.
  • Thermal/processing notes: Avoid overheating; if forming acid chlorides, manage HCl/SO2 evolution. Aryl halides are generally stable but avoid strong nucleophiles at elevated temperature unless part of intended synthesis.

Always defer to the current SDS and institutional risk assessments before use.

Solvent Selection

• Polarity/behavior (general for arylalkyl carboxylic acids)

  • Weak acid; exists as neutral acid in non-basic organics and as carboxylate in basic aqueous media.
  • Preferred solvents for handling/stock solutions: DMSO, DMF, NMP (high solubility); EtOAc, MeOH/EtOH (moderate); DCM/CHCl3 (moderate); poor in aliphatic hydrocarbons.

• Miscibility and extraction

  • Workups often benefit from basify–extract–acidify cycles: dissolve in base (NaHCO3/Na2CO3), wash organics, then re-acidify to precipitate/extract the free acid into an organic solvent (EtOAc/MTBE).
  • For salt formation or crystallization screening, water/MeOH/IPA with controlled pH are common.

• When to choose alternatives

  • If moisture-sensitive transformations (e.g., acid chloride formation) are planned, use dry solvents (toluene, THF, DCM) and exclude water.
  • For cross-couplings on the aryl chloride, toluene, 1,4-dioxane, or CPME with inorganic base (K3PO4, Cs2CO3) are typical; polar aprotics (DMF/DMAc) can accelerate but are less green.

• Small comparison (general)

  • DMF/DMSO: Highest solubility; difficult removal. THF/2-MeTHF: good balance of solubility/volatility. EtOAc: greener, good for extractions and crystallizations. Toluene: good for high-temperature couplings; hydrophobic.

Storage & Reconstitution

• Item-specific

  • Storage conditions: Room temperature (as provided in Product Data). Store tightly closed in a dry, well-ventilated place away from incompatible materials.
  • Shipping: Shipped under normal conditions.

• General guidance for this compound class

  • Stability: Aromatic carboxylic acids with aryl halides are typically bench-stable. Protect from prolonged exposure to moisture if the free acid could form hydrates; avoid strong light/heat during long-term storage.
  • Container: Amber glass or HDPE with PTFE-lined cap recommended for long-term storage; include desiccant if in humid environments.
  • Reconstitution/solution preparation: Prepare stock solutions in dry DMSO, DMF, NMP, MeOH, EtOH, EtOAc, DCM, or mixtures thereof, depending on intended use. For moisture-sensitive downstream steps (e.g., acid chloride formation), ensure anhydrous solvents and inert atmosphere.
  • Freeze–thaw: Not typically applicable to solids. If storing solutions, aliquot and store under inert gas at 2–8°C or −20°C to minimize hydrolysis/oxidation; avoid repeated freeze–thaw cycles.

For any lot-specific handling nuances (e.g., appearance, residual solvent), consult the CoA/Spec Sheet and SDS.

Structure & Identity

A halogenated arylalkyl carboxylic acid featuring an ortho-chloro and para-fluoro pattern on a benzene ring bearing a 3‑carboxypropyl substituent (3-(2-chloro-4-fluorophenyl)propanoic acid).

• Item-specific (from Product Data)

  • Product name: 2-Chloro-4-fluoro-benzenepropionic acid (SKU: C299488)
  • CAS: 174603-38-4
  • PubChem CID: 11769583
  • InChIKey: 55486 (as provided)
  • Storage conditions: Room temperature; shipped under normal conditions
  • Research use: For research use only

• Literature/computed identifiers and features (informational; not item specifications)

  • Synonym: 3-(2-chloro-4-fluorophenyl)propanoic acid
  • Proposed SMILES: O=C(O)CCc1c(Cl)ccc(F)c1
  • Proposed molecular formula: C9H8ClFO2
  • Calculated molecular weight: ~202.45 g/mol (from formula)
  • Functional groups: Aromatic ring; aryl chloride (C–Cl); aryl fluoride (C–F); aliphatic carboxylic acid (–CO2H)
  • Structural description (2D): A benzene ring substituted at C1 by a –CH2–CH2–CO2H chain, at C2 by Cl (ortho to side chain), and at C4 by F (para to side chain); no stereocenters.

• Not specified for this item; refer to CoA/Spec Sheet for authoritative structural identifiers (SMILES/InChI/InChIKey, MF/MW if required).

Synthetic Utility

• Orthogonal functional handles

  • –CO2H: convertible to amides, esters, acyl chlorides, anhydrides, and RAEs for decarboxylative couplings.
  • Aryl C–Cl: competent in Pd-catalyzed Suzuki/Miyaura borylation, Buchwald–Hartwig amination, Negishi/Stille couplings; also amenable to directed metalation/halogen–metal exchange.
  • Aryl C–F: generally inert under standard cross-coupling, enabling selective monofunctionalization; can be engaged under harsh conditions (e.g., borylation with special catalysts, or SNAr only with strong activation elsewhere).

• Retrosynthetic value

  • Can serve as a convergent node: build the side chain via carboxyl chemistry, then diversify the aryl chloride; or pre-functionalize the aryl ring and introduce the acid via homologation (e.g., Ar–CH2–CH2–CN → hydrolysis).
  • Carboxyl as directing group: temporary masks (Weinreb amide) facilitate controlled acylations; conversion to acyl fluoride (DAST alternatives not applicable) enables mild coupling.

• Downstream diversification

  • Install boronate at C–Cl (Pd/dppf or XPhos), then iterate Suzuki to furnish biaryl arrays while retaining para‑F.
  • Curtius to isocyanate → urea/carbamate libraries anchored on the 2‑Cl,4‑F arylpropyl scaffold.
  • RAEs for Ni/photoredox decarboxylative arylation/alkylation expanding beyond classical two-electron chemistry.

Target Specificity

Not applicable. This product is a small-molecule chemical building block, not a biological macromolecule or affinity reagent. No antigen/epitope, clone, isotype, or species reactivity information applies.

Frequently Asked Questions

What is the purity of this product?

This product is supplied at ≥98% purity (chemical assay). Lot-specific values are stated on the Certificate of Analysis.

How should this product be stored?

Store at room temperature.

How is this product shipped?

This product ships under standard ambient conditions. No temperature-controlled packaging is required.

What are the CAS number, molecular formula and molecular weight?

The CAS Number is 174603-38-4, the molecular formula is C9H8ClFO2, and the molecular weight is 202.61 g/mol. InChIKey CWLAMJYAQMNGPA-UHFFFAOYSA-N.

What documentation is provided?

Available product documentation, including Certificates of Analysis (COA), Safety Data Sheets (SDS), and specification sheets, is shown in the product document area. Document availability and access follow the current site policy.