Ethyl 4-bromo-2,3-dimethylbenzoate - ≥95% , CAS No.1804403-79-9

CAS: 1804403-79-9 Cat. No.: E973019 Formula: C₁₁H₁₃BrO₂ Peso molecolare: 257.120

GRADE & PURITY ≥95%

Storage

Room temperature

Specifications

Specifiche e purezza

≥95%

Condizioni di conservazione di stoccaggio

Room temperature

Purezza

≥95%

Nomi e identificatori

• Sorrisi canonici: CCOC(=O)C1=C(C(=C(C=C1)Br)C)C
• IUPAC Name: ethyl 4-bromo-2,3-dimethylbenzoate
• InChIKey: YENASFHZCMLMNN-UHFFFAOYSA-N
• INCHI: 1S/C11H13BrO2/c1-4-14-11(13)9-5-6-10(12)8(3)7(9)2/h5-6H,4H2,1-3H3
• Peso molecolare: 257.120

Proprietà chimiche e fisiche

• Peso molecolare: 257.120 g/mol
• XLogP3: 3.600
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 3
• Exact Mass: 256.01 Da
• Monoisotopic Mass: 256.01 Da
• Topological Polar Surface Area: 26.300 Ų
• Heavy Atom Count: 14
• Formal Charge: 0
• Complexity: 205.000
• 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 application protocols (e.g., WB, IHC, IF, FC) apply to this small-molecule building block. For synthetic applications, refer to the Reaction Conditions and Synthetic Utility tabs for representative procedures and optimization guidance.

Biological Roles

This product is a small-molecule synthetic intermediate (aryl bromide ester) and is not intended for biological role studies. It is not a natural metabolite, cofactor, or biopolymer component. Any biological interactions would be nonspecific hydrophobic binding typical of substituted aromatic esters.

• Research use note: For research use only (per Product Data). Not for human or veterinary use.

• General chemistry perspective:

  • The molecule is neutral, lipophilic, and lacks ionizable functionality; it is unlikely to engage in specific enzymatic roles without designed context.
  • If incorporated into SAR studies, the ester can serve as a masked acid; hydrolysis in biological matrices may occur, but rates are highly context-dependent and must be determined experimentally.

For biochemistry-focused work, prefer dedicated biochemical reagents or characterized ligands; this catalog item is best viewed as a chemical building block for upstream synthesis rather than a probe.

Buffer Applications

Not typically applicable. Ethyl 4-bromo-2,3-dimethylbenzoate is a hydrophobic organic building block and does not function as a buffering agent. If used in assays or extractions, prepare stock solutions in compatible organic co-solvents (e.g., DMSO, THF, EtOH) and dilute into the assay buffer within the tolerated organic percentage.

Green Alternatives

While this item is a building block (not a solvent), its use commonly involves choices that impact sustainability, notably solvent selection and cross-coupling methodology. Consider the following greener strategies (literature-based):

• Greener solvent swaps for common operations:

  • Replace dioxane/DMF with 2-MeTHF, CPME, toluene, or propylene carbonate where compatible with catalyst/base and solubility.
  • Favor ethanol/water co-solvent systems in Suzuki couplings when feasible.

• Catalyst and coupling strategy:

  • Use ligand-efficient Pd or Ni systems at ppm levels; heterogeneous catalysts or supported Pd can aid recovery.
  • Employ base- and aqueous-tolerant systems to reduce organic solvent volumes.

• Avoiding halogen where possible: Not directly applicable to this fixed aryl bromide substrate; however, analogous cross-couplings can sometimes start from carboxylate derivatives (decarboxylative couplings) to avoid prehalogenation.

• Comparison snapshot (qualitative):

  • 1,4-Dioxane vs 2-MeTHF: 2-MeTHF is bio-derived, lower toxicity, higher hydrophobicity; dioxane offers water miscibility but is classified with greater health concerns.
  • DMF/DMAc vs acetonitrile/Me-THF: MeCN and 2-MeTHF present improved EHS profiles and easier removal; DMF/DMAc provide high polarity but have reproductive toxicity concerns.

• Workup/waste minimization:

  • Favor in situ generated boronates and aqueous micellar catalysis (e.g., surfactant-enabled Suzuki) to reduce organic solvent usage.
  • Plan telescoped ester conversions (e.g., coupling → direct amidation without isolation) to reduce solvent cycles.

Tradeoffs: Greener solvents may change rate/solubility and require catalyst/base re-optimization. Always confirm performance at scale with appropriate DoE.

Pharmaceutical Uses

This product is offered for research use only and is not an excipient or API. No pharmacopeial status is provided in the Product Data.

• Potential roles in pharmaceutical R&D (general):

  • Synthetic intermediate: The aryl bromide enables rapid diversification by cross-coupling to generate analog libraries. The ethyl ester can be converted to the corresponding acid, amide, or alcohol for property tuning.
  • Process development: Useful in studying steric/electronic effects of 2,3-dimethyl substitution on benzoate cores.

• Formulation considerations: As a hydrophobic small molecule lacking ionizable groups, it is not suitable as a buffering or stabilizing excipient. If handled in formulation labs (e.g., as an impurity standard or synthetic intermediate), dissolve in appropriate organic solvents and avoid aqueous systems.

No therapeutic or clinical claims are made or implied. Refer to internal quality systems for any GMP-adjacent usage.

Physical Properties

Item-specific physicochemical specifications have not been provided for this catalog entry. The following guidance distinguishes between unspecified values for this item and general/literature expectations for the compound class.

• Appearance (Product Data): Not specified for this item; refer to CoA/Spec Sheet.
• Molecular formula (literature/inferred): C11H13BrO2
• Molecular weight (literature/computed): ~257.12 g/mol
• Melting/boiling point: Not specified for this item; consult SDS/CoA. Aromatic ethyl benzoates with ring substitution are typically low-melting liquids or low-melting solids with high boiling points (>250 °C) under ambient pressure (literature, qualitative).
• Density, refractive index, viscosity: Not specified for this item; refer to CoA/Spec Sheet.
• Solubility (qualitative, literature):
  • Expected to be insoluble in water and miscible or highly soluble in common organic solvents (e.g., dichloromethane, chloroform, toluene, THF, ethyl acetate, acetone).
• LogP/partitioning (qualitative, literature): Aromatic ester with bromine and two methyls suggests moderate-to-high hydrophobicity (logP likely >3), favoring organic phases.
• pKa: Not applicable (no ionizable groups in neutral range); carboxylate is masked as an ethyl ester.

Note: For method validation, chromatographic method setup, or density-sensitive handling, obtain lot-specific values from the Aladdin CoA/Spec Sheet. Avoid using literature values as acceptance criteria for QC without internal verification.

Quality and Grades

• Grade/purity (Product Data): Not specified for this item; refer to CoA/Spec Sheet for assay, impurity profile, and chromatographic purity.

• What to expect from research-grade aryl bromide esters (general guidance):

  • Assay typically reported by GC or HPLC area% with complementary 1H NMR integration; residual solvents, water (Karl Fischer), and inorganic halides are often controlled but may not be universally specified.
  • Metallic impurities are rarely specified for small-molecule building blocks unless intended for catalysis-sensitive steps; check CoA if ppm limits are critical.

• Stabilizers/inhibitors: None indicated in Product Data. If sensitive transformations are planned (e.g., low-level Pd-catalyzed couplings), pre-treat with basic alumina or silica only after confirming no ester hydrolysis; otherwise, use as received.

• Documentation and traceability:

  • Request the lot-specific CoA for assay, residual solvents, and identity confirmation (NMR/LC-MS/HRMS where available).
  • If using for GMP-adjacent research, qualify incoming material with orthogonal ID tests (1H/13C NMR, GC/LC retention match, HRMS) and define acceptance criteria internally.

• Practical note: For cross-coupling, trace adventitious acid or base can affect catalyst speciation. If purity is not specified, consider quick preps (filtration, short plug) to remove polar micro-impurities that could poison catalysts.

Reaction and Applications

Ethyl 4-bromo-2,3-dimethylbenzoate is a versatile aryl bromide–ester synthon. The Ar–Br enables metal-catalyzed cross-coupling, while the ethyl benzoate can be orthogonally transformed to acids, amides, or alcohols.

• Cross-coupling (literature):

  • Suzuki–Miyaura: Couples with aryl/alkenyl/alkyl boron reagents under Pd catalysts (e.g., Pd(PPh3)4, Pd(dppf)Cl2) with bases such as K2CO3, K3PO4, Cs2CO3 in toluene/EtOH/H2O or dioxane/H2O. The para-bromide to the ester is typically reactive; 2,3-dimethyl groups add mild steric bulk but generally allow coupling.
  • Buchwald–Hartwig amination: Formation of anilines/anilides using Pd precatalysts and dialkylbiaryl phosphines; use NaOtBu or Cs2CO3 in toluene/dioxane.
  • Negishi/Kumada/Stille: Formation of C–C bonds with organozinc, Grignard, or stannanes; take ester compatibility into account (protect from nucleophilic attack).

• Halogen–metal exchange (literature):

  • iPrMgCl·LiCl (Turbo Grignard) or n-BuLi can effect Br–Mg/Li exchange at low temperature to generate the aryl metal reagent for subsequent electrophile trapping (e.g., formylation, borylation). Stringent temperature control is required to avoid ester reduction or addition.

• Ester transformations (orthogonal):

  • Hydrolysis to acid (basic or acidic), followed by amidation or coupling.
  • Reduction to benzyl alcohol derivative (LiAlH4, DIBAL-H) with caution to avoid Ar–Br reduction.
  • Direct aminolysis or transesterification under catalytic conditions.

• Electrophilic aromatic substitution: Remaining positions are deactivated by the ester but activated by methyls; further EAS is generally less predictable and cross-coupling is preferred for regiocontrol.

• Applications: Useful intermediate for substituted toluate scaffolds, agrochemical discovery, materials monomers, and late-stage diversification via coupling/functional group interconversion.

Reaction Conditions

The following conditions are general literature guidance for aryl bromide esters of this class; optimize per substrate/catalyst.

• Suzuki–Miyaura arylation:

  • Catalyst: 1–3 mol% Pd(PPh3)4 or 1–2 mol% Pd(dppf)Cl2; for hindered partners, use dialkylbiaryl phosphine ligands.
  • Base: K3PO4 (2–3 equiv), K2CO3, or Cs2CO3.
  • Solvent: 1,4-dioxane/H2O (3:1), toluene/H2O, or 2-MeTHF/H2O.
  • Temperature: 60–100 °C; 2–12 h. Higher temperatures may be needed for sterically demanding couplings.

• Buchwald–Hartwig amination:

  • Catalyst: Pd2(dba)3 (0.5–1 mol% Pd) + BrettPhos/RuPhos, or precatalysts.
  • Base: NaOtBu or Cs2CO3 (2–3 equiv).
  • Solvent: Toluene or dioxane; 80–110 °C; 4–16 h.

• Bromine–metal exchange (for formylation/borylation):

  • n-BuLi (1.0–1.2 equiv) in anhydrous THF or Et2O at −78 to −40 °C, 10–30 min, then trap with DMF (for aldehyde) or B(OMe)3/pinacol/B2pin2 (for boronate). Carefully control temperature to avoid ester addition/reduction; Turbo Grignard (iPrMgCl·LiCl) at −20 to 0 °C can be milder toward esters.

• Ester conversions:

  • Hydrolysis: KOH/MeOH/H2O (basic) or HCl/EtOH (acidic), rt–60 °C, 1–6 h.
  • Amide coupling: Convert to acid (TFA or base hydrolysis), then EDCI/HOBt, HATU, or CDI in DMF/DCM with base (DIPEA), rt–40 °C, 1–12 h.

• Analytical monitoring: LC–MS (APCI/ESI) readily detects Br isotopic pattern (M and M+2). Use inert atmosphere for metal-catalyzed couplings; rigorously dry solvents.

Safety and Handling

Safety information specific to this item (GHS classification, hazard statements, pictograms) is not provided in the Product Data. Always review the Aladdin SDS for authoritative guidance before use.

• GHS/SDS:
  • Signal word / H-statements / Pictograms: Not specified for this item; refer to SDS.
• General hazards (class-based, literature): Aromatic bromides and esters are commonly classified as irritants; avoid inhalation of vapors/aerosols and contact with skin/eyes. Combustible organic liquid/solid; keep away from ignition sources.
• PPE: Wear chemical-resistant gloves (e.g., nitrile), lab coat, safety glasses or splash goggles. Use in a fume hood to control vapors and dust/aerosols.
• Handling notes:
  • Avoid strong bases if ester integrity is required (risk of saponification/transesterification).
  • Aryl bromides may undergo metalation; keep away from reactive metals and strong nucleophiles unless intended.
  • Prevent release to the environment; halogenated aromatics can be persistent.
• Incompatibilities (general): Strong bases (for ester stability), strong oxidizers (combustion risk), strong reducing agents/organometallics (may attack the ester or aryl–Br bond).
• First aid (overview; defer to SDS):
  • Inhalation: Move to fresh air, seek medical advice if symptoms persist.
  • Skin/eye contact: Rinse with water for at least 15 minutes; remove contaminated clothing; seek medical advice if irritation develops.
  • Ingestion: Rinse mouth, do not induce vomiting; get medical attention.
• Fire response: Use CO2, dry chemical, or foam. Combustion may produce CO/CO2 and HBr; firefighters should wear SCBA.

Solvent Selection

This product is a synthetic building block rather than a solvent. Selection of reaction or processing solvent should be guided by the chemistry planned for the aryl bromide and/or the ester.

• Polarity and solubility (qualitative): Hydrophobic aromatic ester; generally soluble in apolar to mid-polar organic media (toluene, xylene, chlorinated solvents, THF, EtOAc, acetone, MeCN), and essentially insoluble in water.

• Typical solvent choices by transformation (literature-based guidance):

  • Pd-catalyzed cross-coupling (Suzuki, Buchwald–Hartwig): 1,4-dioxane/water, toluene, THF, or Me-THF; base and water content tuned to catalyst.
  • Ni-catalyzed couplings/reductive couplings: DMAc, NMP, THF, 2-MeTHF, or dioxane; use dry, degassed conditions.
  • Lithium–halogen exchange: Anhydrous Et2O or THF at −78 to −20 °C (avoid ester reduction by controlling temperature and stoichiometry).
  • Ester hydrolysis/amidation: MeOH/THF/H2O (basic or acidic), or amide coupling in DMF/DCM/MeCN with coupling reagents.

• Workup/extraction: Partition effectively into DCM/EtOAc from aqueous phases; salting out can improve phase separation due to hydrophobicity.

• Small comparison (qualitative):

  • Toluene vs dioxane: Toluene is greener and higher boiling; dioxane offers miscibility with water and often higher coupling rates but has more stringent EH&S concerns.
  • THF vs 2-MeTHF: 2-MeTHF is a greener alternative with similar solubility and higher hydrophobicity (see Green Alternatives tab).

Storage and Reconstitution

• Storage (Product Data): Room temperature.
• Container: Store tightly closed in an amber glass bottle to minimize photolysis and oxidative discoloration. Purge headspace with inert gas if long-term storage and frequent openings are expected.
• Atmosphere: Keep dry; esters can hydrolyze slowly in the presence of moisture and base.
• Stability: Aryl bromide esters are generally stable under ambient conditions when protected from light and moisture. Avoid prolonged exposure to strong acids/bases and high temperatures.
• Reconstitution/Preparation: Not applicable; supplied as a neat small molecule. For solution preparation, dissolve in a compatible anhydrous organic solvent (e.g., DCM, toluene, THF, EtOAc, MeCN). Prepare reaction solutions under inert atmosphere for metal-catalyzed couplings.
• Freeze–thaw: Not relevant to neat solids/liquids; if preparing stock solutions, store in sealed, moisture-free vials at 2–8 °C or room temperature depending on solvent, and avoid repeated warming/cooling cycles to limit peroxide formation in ethers and solvent evaporation.
• Shipping: Not specified for this item; refer to CoA/Spec Sheet. Typically ships as a non-hazardous or limited-quantity organic chemical unless otherwise noted in SDS.

Always consult the Aladdin SDS for definitive handling and storage recommendations.

Structure and Identity

Ethyl 4-bromo-2,3-dimethylbenzoate is an aryl bromide bearing an ethyl benzoate ester and two adjacent methyl substituents on the ring. It serves as a multifunctional building block combining a cross-coupling handle (Ar–Br) with a transformable carboxylate ester.

• Item identifiers (Product Data):

  • SKU: E973019
  • Product Name: Ethyl 4-bromo-2,3-dimethylbenzoate
  • CAS: 1804403-79-9
  • PubChem CID: 121229121
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.

• Composition/Formula:

  • Molecular formula (literature/inferred from name): C11H13BrO2
  • Molecular weight (literature/computed): ~257.12 g/mol (C11=132.11, H13=13.13, Br=79.90, O2=32.00)

• Structural features (descriptive):

  • Aromatic ring with substituents at positions 1 (ethyl ester, –CO2Et), 2 and 3 (–CH3), and 4 (–Br) relative to the carbonyl carbon as position 1.
  • Functional groups: aryl bromide (cross-coupling handle), ethyl ester (amenable to hydrolysis, reduction, amidation), and two ortho/meta methyl groups (steric/electronic modulation).
  • 2D description: a benzene core; para to the ester is bromine; adjacent to the ester on both ortho and ortho′ sides are methyl groups; the ethyl ester extends from the carboxyl carbon with a –CH2–CH3 chain.

• Stereochemistry: None (achiral, no stereogenic centers).

Synthetic Utility

This scaffold integrates three modular elements that facilitate convergent synthesis:

• Aryl bromide (para to the ester):

  • Readily engages in Pd- or Ni-catalyzed cross-couplings (Suzuki, Buchwald–Hartwig, Negishi, Kumada, Stille), enabling C(sp2)–C and C(sp2)–N/O/S bond formation with broad partner scope.
  • Compatible with borylation (Miyaaura) to access the corresponding pinacol boronate for subsequent iterative coupling.

• Ethyl ester:

  • Orthogonal handle for late-stage derivatization: hydrolysis to acid, Curtius/Schmidt chemistry from the acid, amide coupling, or chemoselective reduction to benzyl alcohols.
  • Provides electron withdrawal that can modulate oxidative addition rates in cross-coupling (often beneficial vs purely electron-rich rings).

• 2,3-Dimethyl substitution:

  • Adds steric bias near the ester, potentially influencing regioselectivity in further functionalization and reducing undesired ortho-metalation proximal to the ester.

Retrosynthetic considerations (literature):

• Disconnections via C–Br: Plan library synthesis by fixing the benzoate core then diversifying via boron partners or amines.
• Orthogonal sequencing: Perform cross-coupling first (to preserve ester), then convert the ester in the final steps; or invert the order if coupling partners are base-sensitive.

Purification/workup tips: The product and analogs often show strong retention on silica due to the aromatic core; hexanes/EtOAc or toluene/EtOAc gradients are effective. Monitor for debromination side-products under hydrogenating or strongly reducing conditions.

Target Specificity

Not applicable. This product is a small-molecule chemical building block and is not an antibody, enzyme, or biological affinity reagent. No target, epitope, clone, or species reactivity information applies.