3-[(2-Bromophenoxy)methyl]benzoic acid - ≥95% , CAS No.438473-78-0

CAS: 438473-78-0 Cat. No.: B1328153 Fórmula: C₁₄H₁₁BrO₃ Peso molecular: 307.143 PubChem CID: 2064014

GRADE & PURITY ≥95%

Storage

Room temperature

Shipped In

Normal

Specifications

Especificaciones y pureza

≥95%

Condiciones de almacenamiento de almacenamiento

Room temperature

Enviado en

Normal

Pureza

≥95%

Nombres e identificadores

Sonrisas canónicas

C1=CC=C(C(=C1)OCC2=CC(=CC=C2)C(=O)O)Br

IUPAC Name

3-[(2-bromophenoxy)methyl]benzoic acid

InChIKey

OGTOSXWRKAZOKL-UHFFFAOYSA-N

INCHI

1S/C14H11BrO3/c15-12-6-1-2-7-13(12)18-9-10-4-3-5-11(8-10)14(16)17/h1-8H,9H2,(H,16,17)

Isómeros SMILES

C1=CC=C(C(=C1)OCC2=CC(=CC=C2)C(=O)O)Br

PubChem CID

2064014

Peso molecular

307.143

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Clase Benzene and substituted derivatives
      • Subclass Benzoic acids and derivatives

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Clase: Benzene and substituted derivatives
• Subclass: Benzoic acids and derivatives
• Intermediate Tree Nodes: Not available
• Direct Parent: Benzoic acids
• Alternative Parents: Phenoxy compounds Phenol ethers Benzoyl derivatives Bromobenzenes Alkyl aryl ethers Aryl bromides Monocarboxylic acids and derivatives Carboxylic acids Organobromides Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Benzoic acid - Phenoxy compound - Benzoyl - Phenol ether - Halobenzene - Bromobenzene - Alkyl aryl ether - Aryl bromide - Aryl halide - Monocarboxylic acid or derivatives - Ether - Carboxylic acid - Carboxylic acid derivative - Organooxygen compound - Organobromide - Organohalogen compound - Hydrocarbon derivative - Organic oxide - Organic oxygen compound - Aromatic homomonocyclic compound
• Descripción: This compound belongs to the class of organic compounds known as benzoic acids. These are organic Compounds containing a benzene ring which bears at least one carboxyl group.
• 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

Propiedades químicas y físicas

• Peso molecular: 307.140 g/mol
• XLogP3: 3.600
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 4
• Exact Mass: 305.989 Da
• Monoisotopic Mass: 305.989 Da
• Topological Polar Surface Area: 46.500 Ų
• Heavy Atom Count: 18
• Formal Charge: 0
• Complexity: 282.000
• 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. No biological assay protocols (e.g., WB, IHC, IF, FC) are associated with this small-molecule reagent. For synthetic use, refer to the Reaction Conditions and Synthetic Utility sections for general laboratory procedures and starting points.

Biological Roles

This product is a synthetic aromatic carboxylic acid building block, not a biological metabolite or cofactor.

• General context (literature)

  • Benzoic acid derivatives can interact with proteins and membranes depending on substitution, but 3-[(2-bromophenoxy)methyl]benzoic acid has no established endogenous biological function.
  • The aryl bromide is a synthetic handle rather than a biological motif; any biological activity would be system- and substituent-specific and must be empirically determined.

• Research use only

  • Per Product Data: For research use only. Not intended for food, drug, household, or cosmetic use.

Buffer Applications

Not typically used as a buffering agent. As a monocarboxylic aromatic acid, it lacks the conjugate acid/base pair characteristics and pKa spacing required for effective laboratory buffer systems.

• Practical note
  • The carboxylate salt can be formed in basic aqueous solutions (e.g., NaHCO3/Na2CO3) to aid extractions or purifications, but this is a workup tactic rather than a buffering application.

Green Alternatives

While the compound itself is a fixed building block, greener choices arise in solvent/coupling reagent selection and halide handling during its use.

• Greener solvent swaps (literature guidance)

  • Replace THF/dioxane with 2-MeTHF or CPME for Pd-catalyzed couplings and esterifications; improved safety (higher boiling point, lower peroxide formation for CPME) and bio-based sourcing (2-MeTHF).
  • Favor EtOAc or MeTHF over DCM for extractions and Steglich esterifications when feasible.
  • Use water or water-organic biphasic systems (e.g., dioxane/H2O → 2-MeTHF/H2O) for Suzuki couplings.

• Reagent choices

  • Amide couplings: EDC/Oxyma or CDI can reduce urea waste vs. DCC; T3P is another lower-hazard dehydrative option (easier workup).
  • Cross-coupling: Employ ligand-efficient Pd systems or Ni catalysts at low loadings; consider micellar catalysis (e.g., TPGS-750-M in water) to reduce organic solvent use.

• Comparison table (general)

  • THF/dioxane vs. 2-MeTHF/CPME: Similar coupling performance; greener profile for 2-MeTHF/CPME; check solubility and catalyst compatibility.
  • DCM vs. EtOAc: EtOAc safer/greener; may require higher temperature or more time.

• Waste and workup

  • Segregate halogenated waste due to aryl bromide. Optimize crystallizations to minimize chromatography. Recycle solvents where validated.

Pharmaceutical Uses

No pharmacopeial or excipient status is specified for this item.

• Item-specific (Product Data)

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

• General context (non-clinical)

  • Compounds of this type are commonly used as synthetic intermediates in discovery chemistry to build libraries of amides, esters, and cross-coupled derivatives. Any use in pharmaceutical research is as a building block under GMP or non-GMP workflows as required. No therapeutic claims are made or implied.

Physical Properties

• Item-specific (Product Data)

  • Appearance: 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 (informational, not product specifications)

  • Empirical formula (from structure name): C14H11BrO3 (literature/computed)
  • Formula weight: ~307.14 g/mol (literature/computed)
  • Physical state/volatility: Aromatic carboxylic acids of this size are typically low-volatility solids with moderate melting points (literature expectation; exact MP/BP not specified for this item).
  • Acid–base: Contains one carboxylic acid (expected pKa for benzoic acids typically ~4.0–4.5; literature generality, not measured for this compound).
  • Solubility profile (general): Poorly soluble in water in neutral form; soluble in common organic solvents (e.g., DCM, THF, EtOAc) and in aqueous base as the benzoate salt (general behavior of aryl benzoic acids; not item-specific).

• Not specified for this item; refer to CoA/Spec Sheet

  • Melting point, boiling point, density, refractive index, logP, UV cutoff, water/peroxide/metal content.

Quality and Grades

• Item-specific (Product Data)

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

• Guidance on grades (general)

  • For synthetic building blocks like aryl bromides/benzoic acids, common grades include “research grade,” “>95% purity,” or “>98% purity.” Higher purity can reduce byproducts in cross-couplings and amide couplings and improve analytical reproducibility.
  • If LC/GC/HPLC suitability is important (e.g., analytical reference work), low-UV and low-residual-solvent specifications are often preferred. Verify by CoA.

• Stabilizers/additives

  • No stabilizer is listed for this item. In general, benzylic aryl ethers and benzoic acids do not require stabilizers. If trace acid is problematic for your chemistry, consider baselining material by triturating or performing a short plug filtration before use.

• Recommended verification

  • Confirm identity and purity via NMR (1H, 13C), HRMS, and HPLC/GC as appropriate. The aryl bromide provides a characteristic isotopic pattern (M/M+2) in MS. Carboxylic acid proton appears broad downfield in 1H NMR; benzylic CH2 as a singlet near 4.9–5.2 ppm (typical literature range).

Reaction and Applications

As a bifunctional building block, 3-[(2-bromophenoxy)methyl]benzoic acid participates in diverse transformations enabling convergent synthesis of biaryls, heteroaryls, and functionalized amides/esters.

• Transformations at the carboxylic acid

  • Amide couplings: HATU/DIPEA, EDC·HCl/HOBt (or Oxyma), T3P, or PyBOP deliver amides with primary/secondary amines. Benzylic ether typically survives standard coupling conditions.
  • Esterifications: Fischer (acid-catalyzed in ROH), Steglich (DCC/DMAP), or via acid chlorides (SOCl2 or oxalyl chloride, then ROH/Et3N). Mixed anhydrides (pivaloyl chloride, isobutyl chloroformate) are viable.
  • Decarboxylative methods: With modern photocatalysis or Ni/Ag catalysis, decarboxylative cross-couplings or radical additions can install diverse groups on the benzylic/aryl framework (literature generality).

• Transformations at the aryl bromide (on the distal ring)

  • Cross-couplings: Suzuki–Miyaura (with boronic acids/esters), Buchwald–Hartwig amination, Sonogashira (terminal alkynes), Heck (olefins), and Kumada/Negishi. Ortho-bromo orientation can influence selectivity and facilitate intramolecular cyclizations.
  • Metal–halogen exchange: With iPrMgCl·LiCl or n-BuLi at low temperature, followed by trapping (formylation, borylation, etc.). Protect carboxyl with base-sensitive precautions or pre-convert to amide/ester.

• Ether linkage

  • Generally stable to bases and moderate acids; cleaves under strong Lewis acids or BBr3 (demethylation-type conditions extend to some benzylic aryl ethers). Can be leveraged for intramolecular cyclization strategies if appropriately functionalized.

• Representative applications

  • Late-stage diversification of benzoic-acid–containing scaffolds.
  • Preparation of ortho-substituted phenyl analogs via Pd-catalyzed chemistry while retaining a coupling handle (the acid) for subsequent derivatization.

Reaction Conditions

The following are literature-style general conditions for analogous substrates; optimize for your system. They are not item-specific specifications.

• Suzuki–Miyaura coupling (at aryl Br)

  • Catalyst: Pd(PPh3)4 (1–3 mol%) or Pd-PEPPSI-type precatalyst (0.5–1 mol%)
  • Base: K2CO3, K3PO4, or Cs2CO3 (2–3 equiv)
  • Solvent: 2-MeTHF/H2O or dioxane/H2O (3:1)
  • Temperature/time: 60–90°C, 2–12 h
  • Notes: Carboxylic acid tolerated; add phase-transfer agent (TBAB) if needed. For steric cases, use SPhos/XPhos ligands.

• Buchwald–Hartwig amination

  • Catalyst/ligand: Pd2(dba)3 (1 mol% Pd) with XPhos or BrettPhos; or precatalysts
  • Base: NaOtBu or K3PO4
  • Solvent: Toluene, tAmOH, or CPME
  • 80–110°C, 6–18 h; acids may require base equivalents to neutralize.

• Sonogashira coupling

  • Pd(PPh3)2Cl2 (1–2 mol%), CuI (2–5 mol%), Et3N or iPr2NH as base
  • THF, MeCN, or 2-MeTHF; 25–60°C, 2–8 h. Copper-free protocols available.

• Amide coupling (from acid)

  • HATU (1.1–1.5 equiv), DIPEA (2–3 equiv), amine (1.0–1.5 equiv)
  • Solvent: DMF, DCM, or MeCN; 0–25°C to RT, 1–6 h. Oxyma/EDC alternatives reduce HOBt hazards.

• Steglich esterification

  • DCC (1.1 equiv), DMAP (0.1 equiv), ROH (2–5 equiv), DCM or EtOAc, 0–25°C, 2–16 h; filter urea byproduct.

• Halogen–metal exchange

  • iPrMgCl·LiCl or n-BuLi (1.1–1.5 equiv) in THF at −78 to −20°C; quench with electrophile (B(OMe)3, DMF, etc.). Protect or neutralize the acid functionality as needed.

Safety and Handling

• Item-specific (Product Data)

  • GHS Classification: Not specified for this item; refer to SDS.
  • Signal Word: Not specified for this item; refer to SDS.
  • H-Statements: Not specified for this item; refer to SDS.
  • Pictograms: Not specified for this item; refer to SDS.
  • Storage Conditions: Room temperature
  • Shipped In: Normal

• General safety considerations (literature/general guidance; defer to SDS for authoritative details)

  • Likely hazards: Carboxylic acids and aryl bromides are commonly classified as irritants; avoid contact with skin, eyes, and clothing. Handle powders to minimize dust generation.
  • PPE: Safety glasses, lab coat, and appropriate chemical-resistant gloves. Use in a fume hood to avoid inhalation of dust or vapors generated during heating.
  • Incompatibilities: Strong bases will form the carboxylate salt; strong oxidizers and strong reducing agents may be incompatible. Avoid strong acids/Lewis acids if ether cleavage is of concern.
  • Fire and reactivity: Non-volatile and not highly flammable, but organic solids can burn; keep away from ignition sources. The aryl bromide may participate in metal-catalyzed reactions—avoid contact with reactive metals except under controlled synthetic conditions.
  • First aid overview: If on skin/eyes, rinse with water for several minutes; if inhaled, move to fresh air; if ingested, rinse mouth. Seek medical attention per SDS guidance.
  • Disposal: Dispose of according to institutional and local regulations for halogenated organic compounds.

Solvent Selection

This compound is an aromatic carboxylic acid with an ether-linked 2-bromophenyl substituent. Solvent choice is usually driven by the planned transformation (couplings vs. amidations) and by solubility.

• Polarity/miscibility (general expectations)

  • Neutral form: sparingly soluble in water; soluble in moderately polar organic solvents such as DCM, THF, 2-MeTHF, EtOAc, acetone, MeCN, toluene, and in strong H-bond donors like MeOH/EtOH.
  • As carboxylate (in base): soluble in aqueous basic media (NaHCO3/Na2CO3/NaOH) and in polar aprotic solvents.

• Typical solvent choices by application

  • Amide coupling: DMF, DMAc, NMP, or DCM with coupling reagents (HATU, EDCI, PyBOP). For greener choices, 2-MeTHF or EtOAc with organo-bases is increasingly used.
  • Esterification (Fischer): Toluene, toluene/Dean–Stark, or MeOH/acid catalysis. Steglich esterification: DCM or THF.
  • Cross-coupling at the aryl bromide: Dioxane/water, THF/water, toluene, CPME, or MeCN, often with aqueous base. 2-MeTHF is a common greener alternative to THF/dioxane.

• Comparison notes

  • DCM vs. EtOAc: DCM offers higher solubility for many aryl acids but has higher environmental concerns; EtOAc is greener but may need warming.
  • THF/dioxane vs. 2-MeTHF/CPME: Greener ethers can deliver comparable outcomes while enabling easier workup and reduced peroxide concerns (especially CPME).

Storage and Reconstitution

• Item-specific (Product Data)

  • Storage Conditions: Room temperature
  • Shipped In: Normal

• General handling guidance

  • Keep container tightly closed in a dry, well-ventilated place. Protect from prolonged exposure to strong light or heat.
  • Hygroscopicity: Aromatic carboxylic acids are generally not highly hygroscopic, but cap promptly after use to prevent moisture uptake and contamination.
  • Reconstitution/solution preparation: Prepare solutions in suitable organic solvents (e.g., DCM, THF, EtOAc, MeCN, MeOH, DMF) according to your application. Filter if necessary through a 0.2 µm PTFE membrane. For aqueous work, convert to the carboxylate with base to enhance solubility.
  • Freeze-thaw: Not applicable to solids; if storing stock solutions, aliquot and store per solvent stability guidelines (e.g., −20°C for DMF or MeCN solutions) and minimize freeze–thaw cycles.

• Shelf life

  • No item-specific shelf-life data are provided; use CoA/Spec Sheet for lot-specific guidance. Under proper storage, aryl carboxylic acids/ethers are typically stable for extended periods.

Structure and Identity

3-[(2-Bromophenoxy)methyl]benzoic acid is an aryl carboxylic acid bearing an ether-linked 2-bromophenyl substituent at the meta position of the benzoate ring.

• Item-specific (Product Data)

  • CAS: 438473-78-0
  • InChIKey: 257574 (as provided)
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.

• Computed/Literature identity (informational)

  • Molecular formula (derived from structure name): C14H11BrO3 (literature/computed)
  • Molecular weight: ~307.14 g/mol (literature/computed)
  • IUPAC-style description: 3-[(2-bromophenoxy)methyl]benzoic acid; consists of a benzoic acid core (–CO2H) substituted at the 3-position by a –CH2–O–Ar group, where Ar is a 2-bromophenyl ring.

• Structural features (general description)

  • Functional groups: carboxylic acid (acidic handle for coupling/esterification), aryl bromide (cross-coupling/metal–halogen exchange), aryl–O–CH2– ether linkage (generally inert under many conditions, but cleavable under strong Lewis/Brønsted acids).
  • Ring systems: two benzene rings connected via a benzylic ether (–CH2–O–) spacer; bromine in the ortho position on the distal ring relative to the ether oxygen.
  • 2D description: Benzoic acid ring with CO2H para to H; at the meta position resides a –CH2–O– group that connects to a second phenyl ring bearing Br at the ortho site. No stereocenters (achiral), rigid aromatic framework.

Synthetic Utility

Key functional handles enable orthogonal diversification:

• Carboxylic acid

  • Rapid access to amides (HATU/EDC/T3P methodologies), esters (Fischer, Steglich), and acid chlorides (SOCl2, (COCl)2) for further elaboration. Carboxylate directing effects can be exploited in C–H activation methodologies (literature generality).

• Aryl bromide (on the 2-bromophenyl ring)

  • Cross-coupling platform: Suzuki (to biaryls), Buchwald–Hartwig (aryl amines), Sonogashira (aryl alkynes), Heck (vinylarenes), and carbonylations (CO insertion to aryl esters/amides). Ortho-bromine can enable intramolecular cyclizations to benzofuran-like motifs if appropriately tethered.
  • Halogen–metal exchange for electrophile trapping (e.g., borylation → boronate esters, formylation → aldehydes). Exercise care with the acid—convert to amide/ester or use Schlenk techniques and low temperatures.

• Benzylic ether linker

  • Contributes rigidity and spatial separation; generally robust to bases/nucleophiles, enabling stepwise chemistry at the acid or aryl bromide without protecting groups.

• Strategy in synthesis

  • Perform cross-coupling first under basic aqueous conditions, then engage the acid in coupling/esterification, or vice versa, depending on solubility and compatibility. The two handles provide a modular route to dual diversification (aryl diversification plus acyl diversification) ideal for SAR campaigns.

Target Specificity

Not applicable. This product is a small-molecule chemical building block and does not possess biological target specificity data (no antigen/epitope, clone, or isotype). Use is in synthetic chemistry research.