Ethyl 3,5-dibromothiophene-2-carboxylate - ≥98% , CAS No.62224-22-0

CAS: 62224-22-0 Cat. No.: E1007981 Summenformel: C₇H₆Br₂O₂S Molekulargewicht: 314.000

GRADE & PURITY ≥98%

Storage

Room temperature

Specifications

Spezifikationen & Reinheit

≥98%

Storage

Room temperature

Reinheit

≥98%

Namen und Kennungen

• Kanonisches Lächeln: CCOC(=O)C1=C(C=C(S1)Br)Br
• IUPAC Name: ethyl 3,5-dibromothiophene-2-carboxylate
• InChIKey: CYQHUIACPXDUIL-UHFFFAOYSA-N
• INCHI: 1S/C7H6Br2O2S/c1-2-11-7(10)6-4(8)3-5(9)12-6/h3H,2H2,1H3
• Molekulargewicht: 314.000

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Klasse Thiophenes
      • Subclass Thiophene carboxylic acids and derivatives

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Klasse: Thiophenes
• Subclass: Thiophene carboxylic acids and derivatives
• Intermediate Tree Nodes: Not available
• Direct Parent: Thiophene carboxylic acids and derivatives
• Alternative Parents: 2,3,5-trisubstituted thiophenes Aryl bromides Vinylogous halides Heteroaromatic compounds Carboxylic acid esters Organooxygen compounds Organobromides Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: 2,3,5-trisubstituted thiophene - Thiophene carboxylic acid or derivatives - Aryl halide - Aryl bromide - Heteroaromatic compound - Vinylogous halide - Carboxylic acid ester - Carboxylic acid derivative - Organic oxygen compound - Organic oxide - Hydrocarbon derivative - Organooxygen compound - Organobromide - Organohalogen compound - Aromatic heteromonocyclic compound
• Beschreibung: This compound belongs to the class of organic compounds known as thiophene carboxylic acids and derivatives. These are compounds containing a thiophene ring which bears a carboxylic acid group (or a salt/ester thereof).
• 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

Chemische und physikalische Eigenschaften

• Molekulargewicht: 314.000 g/mol
• XLogP3: 3.900
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 3
• Exact Mass: 313.843 Da
• Monoisotopic Mass: 311.846 Da
• Topological Polar Surface Area: 54.500 Ų
• Heavy Atom Count: 12
• Formal Charge: 0
• Complexity: 177.000
• 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 antibody/assay-specific or bioanalytical application protocols are associated with this small-molecule building block. For synthetic use, refer to the Reaction Conditions, Synthetic Utility, and Reaction & Applications sections for practical guidance.

Biological Roles

This compound is a synthetic, non-natural, halogenated heteroaromatic ester used primarily as a building block in chemical synthesis. It does not have established endogenous biological roles.

• No known roles in primary metabolism or signaling pathways (literature).
• In research contexts, thiophene-containing scaffolds can be explored as fragments or cores in structure–activity relationship studies; however, any biological activity would arise from downstream derivatives rather than from this reagent itself.
• Materials science: 3,5-disubstituted thiophene-2-carboxylate derivatives frequently appear in conjugated oligomers/polymers used in organic electronics; biological interaction is not the focus.

For laboratory safety in biological settings:

• Treat as a general organic chemical with potential cytotoxicity; avoid exposure to cell cultures except under controlled experimental design.

No medical or clinical claims are made; this product is for research use only (Product Data).

Buffer Applications

Not typically applicable. Ethyl 3,5-dibromothiophene-2-carboxylate is a hydrophobic organic building block and is not used as a buffering agent. For aqueous work, select standard biological buffers (e.g., phosphate, HEPES) and dissolve this compound in a biocompatible co-solvent if needed for dosing into aqueous systems.

Green Alternatives

While the substrate itself is a halogenated heteroaromatic (not inherently “green”), process greenness can be improved by solvent and base choices, and by using more benign coupling partners.

Greener process options (literature/analogy):

• Solvents: Replace chlorinated solvents with 2-MeTHF, CPME, toluene, or bio-derived esters when compatible with catalysts and bases.
• Aqueous/micellar catalysis: Consider micellar Suzuki couplings (e.g., TPGS-750-M in water) to minimize organic solvent usage.
• Bases: Favor carbonate/phosphate bases over strong hydroxides to reduce corrosion and salt load.
• Coupling partners: Use organoboron reagents (Suzuki) over stannanes (Stille) to avoid organotin toxicity and waste.

Compact comparison (literature/analogy):

• DCM/CHCl3 vs 2-MeTHF/CPME
  • Safety/environment: Chlorinated solvents have higher environmental impact; 2-MeTHF/CPME are considered greener with favorable life-cycle metrics.
  • Performance: 2-MeTHF often matches THF reactivity and tolerates water; CPME offers low peroxide formation and broad solubility.
• DMF/NMP vs Cyrene/PC/green esters
  • Alternatives like Cyrene or propylene carbonate may work in some couplings; verify catalyst compatibility.

Trade-offs:

• Greener solvents can alter catalyst solubility and rate; small-scale scouting is recommended.
• Micellar systems may require surfactant removal steps in workup.

Note: Substrate halogens are intrinsic to reactivity; minimizing excess and maximizing coupling efficiency improve overall E-factor.

Pharmaceutical Uses

No pharmacopeial or excipient status is provided for this item. It is best regarded as a synthetic intermediate for discovery chemistry rather than a formulation component.

• Excipient role: Not specified for this item; refer to CoA/Spec Sheet.
• Typical R&D use (literature/analogy): As a halogenated heteroaryl ester, it can serve as a precursor to libraries of thiophene-containing amides, acids, alcohols, and biaryls for structure–activity exploration.
• Regulatory note: For research use only (Product Data). Not for diagnostic or therapeutic applications.

Process considerations for discovery support:

• If used in parallel synthesis, validate residual bromide content in final APIs/intermediates per internal specifications.
• Ensure removal of Pd (or other catalyst metals) after coupling (e.g., through scavengers, activated carbon) in medicinal chemistry workflows.

Physical Properties

Item-specific measured physical constants are not provided in the Product Data. Do not treat the following as product specifications; consult the CoA/Spec Sheet for definitive values.

• Appearance: Not specified for this item; refer to CoA/Spec Sheet. (Product Data)
• Boiling point / Melting point: Not specified for this item; refer to CoA/Spec Sheet.
• Density, refractive index: Not specified for this item; refer to CoA/Spec Sheet.
• Solubility (general expectations, literature/analogy):
  • Expected to be soluble in common organic solvents (e.g., dichloromethane, chloroform, toluene, THF, ethyl acetate) due to its nonpolar/weakly polar heteroaryl core and ester functionality.
  • Poorly soluble in water (typical for thiophene esters with dihalogenation).
• Partitioning (qualitative, literature/analogy): Moderate hydrophobicity is expected from two aryl bromides; the ester adds limited polarity.
• UV/Vis (qualitative): Thiophene chromophore absorbs in the near-UV; no item-specific cutoff is available.

Practical implications:

• For analytical HPLC/GC method development, begin with non-aqueous or mixed organic mobile phases; adjust based on observed retention.
• For recrystallization (if solid), candidate solvents often include hexanes/EtOAc or toluene/EtOH systems; for oils, consider bulb-to-bulb distillation or column chromatography.

Reminder: When precise numerical data (mp, bp, density) are required for process design, obtain the lot-specific CoA/Spec Sheet.

Quality and Grades

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

Interpretation and practical notes:

• In the absence of a stated grade (e.g., “98%,” “HPLC grade,” or “AR”), treat the material as a general research-grade reagent suitable for synthetic, analytical method development, and materials R&D. Verify impurity profiles (halide content, residual solvents, and potential debrominated/overbrominated congeners) on the lot-specific CoA when process sensitivity is high.
• For cross-coupling applications, trace metal contamination is typically not limiting; however, if you are developing metal-catalyzed transformations where background metals can poison catalysts, consider passing the reagent through short silica or performing a quick 1H NMR QC to confirm integrity prior to use.
• UV absorbance specifications (for chromatographic use) are not provided. If low-UV background is critical, evaluate by baseline scans in your mobile phase.
• Water/peroxide/metal limits: Not specified for this item; refer to CoA/Spec Sheet.

Documentation:

• Certificate of Analysis (CoA) and Specification Sheet should be requested for batch-specific purity, identity (NMR/HRMS/GC/LC), and handling notes.

Reaction and Applications

Ethyl 3,5-dibromothiophene-2-carboxylate is a versatile bifunctional heteroaryl building block. The two aryl–Br positions enable iterative or double cross-couplings while the 2-ester remains available for orthogonal transformations.

Representative application families (literature/analogy):

• Cross-couplings on aryl bromides: Suzuki–Miyaura, Stille, Negishi, Kumada; access to 3,5-disubstituted thiophene-2-carboxylates for materials (OPV, OLED) and medicinal chemistry scaffolds.
• Halogen–lithium exchange: n-BuLi/t-BuLi at low temperature to form 3- or 5-lithiated intermediates, followed by electrophile trapping (formylation, acylation, borylation). Control conditions to avoid ester enolization/transesterification.
• Direct borylation: Pd-catalyzed Miyaura borylation to yield bis-boronates for subsequent diversification.
• Ester chemistry: Hydrolysis to the corresponding acid (thiophene-2-carboxylic acid derivative), amidation (EDC/HOBt, HATU) after hydrolysis or via direct ester–amide exchange under forcing conditions; reduction (DIBAL-H) to the aldehyde or alcohol (protect ester selectivity relative to aryl–Br).

Practical tips:

• Use dry, degassed solvents; oxygen and water reduce catalytic efficiency in cross-coupling.
• Thiophenes can coordinate to Pd; ligands with appropriate steric/electronic profiles (e.g., SPhos/XPhos) often enhance rates.
• Sequential couplings: If differentiation between C3 and C5 is needed, leverage steric/electronic bias or temperature/ligand control; otherwise, expect similar reactivity.
• Monitor for debromination; add sacrificial halide sources or adjust base/ligand to suppress.

Reaction Conditions

General literature guidance for aryl bromide couplings and heteroaryl ester transformations. These are not product specifications; optimize for your system.

• Suzuki–Miyaura coupling (heteroaryl–Br):
  • Catalyst/ligand: Pd(PPh3)4 (2–5 mol%), Pd2(dba)3 (1–2 mol%) with SPhos/XPhos (2–4 mol%).
  • Base: K2CO3, K3PO4, or Cs2CO3 (2–3 equiv).
  • Solvent: 1,4-dioxane/H2O (3:1), THF/H2O, or toluene/H2O.
  • Temperature/time: 70–100 °C, 4–18 h; monitor for debromination.
• Stille coupling:
  • Catalyst: Pd(PPh3)4 (2–5 mol%) or Pd2(dba)3/P(o-tol)3.
  • Solvent: Toluene or DMF; 80–110 °C.
• Negishi/Kumada:
  • Reagents: R–ZnX or R–MgX′; catalysts such as Pd(dppf)Cl2 (1–3 mol%). THF often preferred; 0–80 °C.
• Halogen–lithium exchange:
  • Base: n-BuLi or t-BuLi (1.0–1.2 equiv per site) in dry THF or Et2O at –78 to –40 °C.
  • Quench: electrophiles (DMF for formylation; B(OMe)3 then oxidative workup for boronic esters).
  • Caution: Protect ester from nucleophilic attack by temperature control and rapid electrophile capture.
• Ester hydrolysis:
  • Basic: K2CO3 or NaOH (aq/alcoholic), rt–60 °C.
  • Acidic: HCl or H2SO4 in MeOH/EtOH; reflux.
• DIBAL-H reduction to aldehyde:
  • Solvent: Toluene or DCM, –78 to –20 °C; 1.0–1.5 equiv DIBAL-H; acidic workup.

Yields: Strongly dependent on substituents/partners; 60–90% is common for well-optimized couplings (literature reports).

Safety and Handling

GHS classification details and pictograms are not provided for this item. The following guidance is general to halogenated heteroaromatic esters; always consult the SDS for authoritative safety information.

• GHS/Signal word/H-statements: Not specified for this item; refer to SDS.
• Likely hazards (general): May cause skin/eye irritation; harmful if swallowed or inhaled; combustible organic liquid/solid; harmful to aquatic life (common for organobromides). Avoid dusts/vapors.
• PPE: Lab coat, safety glasses or splash goggles, and appropriate chemical-resistant gloves (e.g., nitrile). Handle in a fume hood to avoid inhalation of vapors or aerosols.
• Storage: Room temperature (Product Data). Keep in a tightly closed container, protected from moisture and strong oxidizers. Store away from strong bases and nucleophiles that could induce transesterification or hydrolysis under forcing conditions.
• Incompatibilities (general): Strong oxidizers; strong bases and strong nucleophiles (may attack the ester); very strong reducing agents (could affect C–Br bonds).
• First aid (overview):
  • Inhalation: Move to fresh air; seek medical attention if symptoms persist.
  • Skin/eye contact: Rinse with water for at least 15 minutes; remove contaminated clothing; seek medical attention if irritation persists.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.
• Spill/accidental release: Contain, absorb with inert material, collect in suitable waste container. Ventilate area and avoid ignition sources.
• Waste: Dispose in accordance with local regulations for halogenated organic waste.

Solvent Selection

This compound is a moderately hydrophobic, halogenated heteroaryl ester. Solvent choice should balance solubility of both substrate and catalysts and the needs of the transformation.

• Polarity class: Low-to-moderate polarity aromatic ester (literature/analogy).
• Expected miscibility/solubility (literature/analogy):
  • Good: DCM, chloroform, toluene, THF, dioxane, ethyl acetate, acetone, DMF/DMAc, NMP.
  • Limited: Alcohols (MeOH/EtOH) depending on temperature.
  • Poor: Water.
• Cross-coupling contexts:
  • Suzuki–Miyaura: 1,4-dioxane/H2O, toluene/H2O, or THF/H2O mixtures commonly used; base choice (K2CO3, K3PO4, Cs2CO3) dictates aqueous content.
  • Stille/Negishi/Kumada: Toluene, THF, or DMF are frequent.
• Purification:
  • Normal-phase silica chromatography with hexanes/EtOAc or hexanes/DCM gradients typically provides good resolution from mono-brominated or debrominated impurities.

Small comparison (literature/analogy):

• Toluene: High boiling, good for Pd-catalyzed couplings with aryl bromides.
• THF/1,4-dioxane: Better for polar bases, supports micellar water content.
• DMF/NMP: Excellent solubility but harder workup; consider for challenging couplings.

Tip: For crystallization, try nonpolar/polar pairs (hexanes/EtOAc); for oils, use high-boiling solvents for thermal treatments (e.g., toluene) and concentrate under reduced pressure.

Storage and Reconstitution

• Storage temperature: Room temperature (Product Data). Protect from moisture and strong light. Keep container tightly closed.
• Shipped in: Not specified for this item; refer to CoA/Spec Sheet.
• Physical state/appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Reconstitution: Not applicable—this item is supplied neat as a small-molecule reagent. If preparing stock solutions, use dry, oxygen-free organic solvents (e.g., toluene, THF, DCM) and store aliquots under inert gas at low temperature when long-term stability is required.
• Freeze–thaw: Not applicable to solids; for solutions, avoid repeated freeze–thaw by aliquoting.
• Shelf life: Refer to CoA/Spec Sheet. Periodically verify integrity by 1H NMR or LC–MS if stored for extended periods.

Note: Always consult the lot-specific CoA and SDS for authoritative handling and stability information.

Structure and Identity

Ethyl 3,5-dibromothiophene-2-carboxylate is a dihalogenated thiophene bearing an ethyl ester at the 2-position, offering two aryl–Br handles for cross-coupling and a preserved ester for subsequent derivatization.

• CAS: 62224-22-0 (Product Data)
• PubChem CID: 13177180 (Product Data)
• InChIKey: Not specified for this item; refer to CoA/Spec Sheet. (Product Data)
• SMILES: Not specified for this item; refer to CoA/Spec Sheet. (Product Data)
• Molecular formula: C7H6Br2O2S (literature/structure-derived)
• Molecular weight: ~313.99 g/mol (literature/structure-derived)

Structural features (described):

• Core: five-membered aromatic thiophene ring (one sulfur heteroatom).
• Substitution pattern: bromine atoms at the 3- and 5-positions; an ethyl carboxylate (–CO2Et) at the 2-position; one remaining ring hydrogen at the 4-position.
• Functional groups: two aryl bromides (electrophilic handles for Pd-catalyzed cross-coupling or halogen–lithium exchange) and an ethyl ester (amenable to hydrolysis, reduction, or amidation).
• 2D depiction in words: a thiophene ring with S at position 1; moving clockwise, position 2 bears –C(=O)OCH2CH3, positions 3 and 5 each bear –Br, and position 4 carries H.

Notes:

• Any stereochemistry is not applicable (planar heteroaromatic).

Synthetic Utility

Key reactivity elements enable orthogonal functionalization strategies:

• Two aryl–Br groups (positions 3 and 5):
  • Pd-catalyzed cross-couplings (Suzuki–Miyaura, Stille, Negishi, Kumada) to introduce aryl, alkenyl, alkyl, or heteroaryl groups.
  • Halogen–lithium exchange (n-BuLi, –78 to –40 °C) followed by electrophile trapping (formylation with DMF; borylation with B(OMe)3 then oxidation or Pd-catalyzed couplings from the boronate).
• Ethyl ester at position 2:
  • Hydrolysis to acid (basic or acidic conditions), then amide coupling (HATU/EDC) to generate amides.
  • Reduction (DIBAL-H) to the corresponding aldehyde at low temperature; LiAlH4 or BH3 can afford the alcohol (protect aryl–Br from side reactions by controlling conditions).
  • Transesterification to tune protecting group properties.

Strategic sequences (literature/analogy):

• Sequential cross-coupling to build unsymmetrical 3,5-disubstituted thiophenes by controlling ligand, temperature, and reagent stoichiometry.
• Build donor–acceptor architectures: couple an electron-rich aryl at one bromide and an electron-poor aryl at the other; retain or convert the ester to modulate electronics/solubility.

Analytical tips:

• Monitor reactions by LC–MS using the bromine isotopic pattern (M and M+2 of equal intensity) to track bromide-containing species.
• 1H/13C NMR: ester signals (quartet/triplet for –CH2CH3) assist in identity confirmation; aromatic region changes track coupling progress.

Target Specificity

Not applicable. This product is a small-molecule synthetic building block and does not have biological target specificity, antigen recognition, isotype, or species reactivity attributes.