4-Bromo-1-ethoxy-2-methylbenzene: Properties & Lab Uses

4-Bromo-1-ethoxy-2-methylbenzene is a halogenated aromatic ether that serves as a versatile building block in organic synthesis, combining an electrophilic bromine handle, an electron-donating ethoxy group, and an ortho methyl substituent on a single benzene scaffold.

IUPAC Name

4-Bromo-1-ethoxy-2-methylbenzene

Molecular Formula

C9H11BrO

Molecular Weight

215.09 g/mol

Functional Groups

Aryl bromide, aryl ether, methyl substituent

Primary Application

Organic synthesis building block and cross-coupling precursor

SKU

B692691

Chemical Structure and Physical Properties

4-Bromo-1-ethoxy-2-methylbenzene (CAS relevant structure: C₉H₁₁BrO, MW 215.09 g/mol) is a trisubstituted benzene derivative bearing three distinct substituents: a bromine atom at the 4-position, an ethoxy (–OC₂H₅) group at the 1-position, and a methyl group at the 2-position. The ethoxy group acts as an electron-donating substituent via resonance, increasing electron density at the ortho and para positions of the ring, while the methyl group provides additional weak electron donation through hyperconjugation. The bromine atom, being a moderate electron-withdrawing group by induction yet weakly electron-donating by resonance, renders the C–Br bond susceptible to oxidative addition in transition-metal-catalyzed reactions. As a liquid or low-melting solid at ambient conditions (exact melting/boiling point data should be confirmed from the certificate of analysis), the compound is generally handled under standard laboratory conditions with appropriate ventilation.

Synthesis Relevance and Cross-Coupling Reactions

The aryl bromide functionality in 4-Bromo-1-ethoxy-2-methylbenzene makes it a highly versatile electrophilic partner in palladium- and nickel-catalyzed cross-coupling reactions. These include Suzuki–Miyaura coupling with arylboronic acids, Negishi coupling with organozinc reagents, Kumada coupling with Grignard reagents, and Heck coupling with alkenes. The electron-rich aromatic ring, conferred by the ethoxy substituent, moderates the reactivity relative to electron-poor aryl bromides, necessitating careful choice of catalyst system and reaction conditions to achieve efficient conversion. Additionally, the aryl C–Br bond may be utilized in lithium–halogen exchange at low temperatures to generate the corresponding aryllithium species, which can then react with a wide range of electrophiles. The ortho-methyl group can introduce steric considerations that influence regioselectivity and coupling efficiency, particularly in sterically demanding transformations.

Applications in Pharmaceutical and Materials Research

Trisubstituted aryl bromides such as 4-Bromo-1-ethoxy-2-methylbenzene are frequently employed as intermediates in the synthesis of active pharmaceutical ingredients (APIs), agrochemicals, and functional materials. The ethoxy-methyl-substituted arene scaffold appears in numerous pharmacophore libraries, where variation of the halide position and electronic character of ring substituents is used to explore structure–activity relationships (SAR). In materials science, analogous electron-rich aryl units are incorporated into conjugated polymers, organic semiconductors, and liquid-crystal mesogens via iterative cross-coupling steps. The compound may also serve as a precursor to the corresponding boronic acid, stannane, or zinc reagent, thereby acting as a nucleophilic equivalent in reversed polarity approaches. Researchers in medicinal chemistry value this building block for its balanced lipophilicity contributed by the ethoxy and methyl groups, which can positively influence ADMET profiles of derived drug candidates.

Handling, Storage, and Safety Considerations

As with all organobromine compounds, 4-Bromo-1-ethoxy-2-methylbenzene should be handled with standard laboratory precautions. Users are advised to consult the Safety Data Sheet (SDS) before use, wear appropriate personal protective equipment (PPE) including nitrile gloves, safety glasses, and a laboratory coat, and work in a well-ventilated fume hood. The compound should be stored in a tightly sealed container away from strong oxidizing agents, strong bases, and moisture, at cool room temperature or as directed on the product label. Disposal must follow local and institutional regulations for halogenated organic waste. Researchers should verify purity by NMR or GC prior to use in sensitive synthetic steps to ensure reproducible results. Aladdin Scientific's product B692691 is supplied with a certificate of analysis (CoA) detailing purity specifications; customers are encouraged to request the CoA for full characterization data.

Frequently asked questions

What cross-coupling reactions is 4-Bromo-1-ethoxy-2-methylbenzene suitable for?

4-Bromo-1-ethoxy-2-methylbenzene is suitable for palladium-catalyzed Suzuki–Miyaura, Negishi, Heck, and Kumada cross-coupling reactions, leveraging its reactive aryl C–Br bond. It can also undergo lithium–halogen exchange to generate an aryllithium nucleophile for further functionalization.

How should 4-Bromo-1-ethoxy-2-methylbenzene be stored to maintain purity?

The compound should be stored in a tightly sealed container at cool room temperature, away from strong oxidizing agents, strong bases, and moisture. Refer to the product label and Safety Data Sheet for specific storage temperature recommendations, and always request the certificate of analysis for purity data.

What is the molecular formula and molecular weight of 4-Bromo-1-ethoxy-2-methylbenzene?

The molecular formula of 4-Bromo-1-ethoxy-2-methylbenzene is C9H11BrO, and its molecular weight is approximately 215.09 g/mol.

Can 4-Bromo-1-ethoxy-2-methylbenzene be used as a pharmaceutical intermediate?

Yes, trisubstituted aryl bromides of this type are widely used as intermediates in the synthesis of active pharmaceutical ingredients and agrochemicals. The ethoxy and methyl substituents provide balanced lipophilicity, which can beneficially influence the ADMET properties of derived drug candidates. Researchers should verify suitability for their specific synthetic route.

References

1. Miyaura, N.; Suzuki, A. Palladium-Catalyzed Cross-Coupling Reactions of Organoboron Compounds. Chemical Reviews 1995, 95 (7), 2457–2483. doi:10.1021/cr00039a007
2. Johansson Seechurn, C. C. C.; Kitching, M. O.; Colacot, T. J.; Snieckus, V. Palladium-Catalyzed Cross-Coupling: A Historical Contextual Perspective to the 2010 Nobel Prize. Angewandte Chemie International Edition 2012, 51 (21), 5062–5085. doi:10.1002/anie.201107017
3. Aladdin Scientific. Product Certificate of Analysis for 4-Bromo-1-ethoxy-2-methylbenzene, SKU B692691. Aladdin Scientific, accessed 2024.

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