1-Bromo-4-(cyclohexyloxy)benzene: Properties & Applications

1-Bromo-4-(cyclohexyloxy)benzene is a para-substituted aryl bromide featuring a cyclohexyloxy ether group, widely employed as a versatile building block in transition-metal-catalyzed cross-coupling reactions and complex organic synthesis.

CAS Number

41649-40-5

Molecular Formula

C₁₂H₁₅BrO

Molecular Weight

255.16 g/mol

Functional Groups

Aryl bromide, alkyl aryl ether

Key Application

Suzuki, Kumada, and Buchwald-Hartwig cross-coupling reactions

Appearance

Colorless to pale yellow liquid or low-melting solid

SKU

B725623

Chemical Identity and Physical Properties

1-Bromo-4-(cyclohexyloxy)benzene (CAS 41649-40-5) is an aryl bromide in which a bromine atom and a cyclohexyloxy (–OC₆H₁₁) group occupy the 1- and 4-positions of the benzene ring, respectively. Its molecular formula is C₁₂H₁₅BrO with a molecular weight of approximately 255.16 g/mol. The compound typically presents as a colorless to pale yellow liquid or low-melting solid at room temperature. The electron-donating cyclohexyloxy substituent modestly activates the aromatic ring toward electrophilic processes while the carbon–bromine bond remains reactive toward oxidative addition with transition-metal catalysts. The ether linkage confers improved lipophilicity relative to the unsubstituted bromobenzene, which is relevant for pharmaceutical and liquid-crystal applications.

Synthesis and Preparation Routes

The most straightforward preparation of 1-Bromo-4-(cyclohexyloxy)benzene involves the O-alkylation of 4-bromophenol with cyclohexanol or a cyclohexyl halide under basic conditions. A typical approach employs 4-bromophenol reacted with cyclohexyl bromide in the presence of a carbonate base such as potassium carbonate (K₂CO₃) in a polar aprotic solvent (e.g., DMF or acetonitrile) at elevated temperature, following a Williamson ether synthesis mechanism. Alternatively, Mitsunobu conditions (triphenylphosphine / DIAD) can be applied to couple 4-bromophenol with cyclohexanol under mild conditions with inversion at the alcohol carbon, though this is less economically attractive for the symmetric cyclohexyl group. The product is typically purified by column chromatography or distillation under reduced pressure.

Applications in Organic and Medicinal Chemistry

As a para-substituted aryl bromide, 1-Bromo-4-(cyclohexyloxy)benzene is a valuable intermediate in a broad range of transition-metal-catalyzed transformations:

• Suzuki–Miyaura coupling: Reacts with aryl- or alkenylboronic acids in the presence of palladium catalysts to form biaryl and aryl-alkene products bearing the 4-(cyclohexyloxy)phenyl motif, useful in drug discovery and materials science.
• Kumada coupling: Couples with Grignard reagents using nickel or palladium catalysts to introduce alkyl or aryl groups at the ipso position.
• Buchwald–Hartwig amination: Serves as an electrophilic coupling partner for the palladium-catalyzed synthesis of diarylamines and related N-aryl compounds.
• Lithiation / metal–halogen exchange: Treatment with n-BuLi or t-BuLi at low temperature generates the corresponding aryllithium species, which can be trapped with electrophiles to deliver diverse 4-(cyclohexyloxy)phenyl-functionalized compounds.
• Liquid crystal research: The cyclohexyloxy-phenyl structural motif is a recognized mesogenic fragment; this compound has been employed as a building block in the synthesis of thermotropic liquid crystal materials.

Handling, Storage, and Safety Considerations

1-Bromo-4-(cyclohexyloxy)benzene should be handled in a well-ventilated fume hood with appropriate personal protective equipment, including nitrile gloves, safety goggles, and a laboratory coat. As an organobromine compound, it should be treated as a potential irritant to skin, eyes, and the respiratory tract. The compound is typically stored at room temperature in a tightly sealed container away from strong oxidizers, strong bases, and ignition sources. Waste disposal must follow local regulations for halogenated organic solvents and compounds. Researchers should consult the current Safety Data Sheet (SDS) provided by Aladdin Scientific prior to use for specific hazard classifications, first-aid measures, and disposal guidelines.

Quality Specifications and Ordering Information

Aladdin Scientific offers 1-Bromo-4-(cyclohexyloxy)benzene (SKU: B725623) for research use. Researchers and procurement teams are encouraged to contact Aladdin Scientific directly or visit the product page for the most current information on available quantities, purity grades, certificates of analysis, and pricing. Bulk quantities may be available upon request. For technical inquiries regarding suitability for specific synthetic applications, our technical support team is available to assist.

Frequently asked questions

What cross-coupling reactions is 1-Bromo-4-(cyclohexyloxy)benzene compatible with?

1-Bromo-4-(cyclohexyloxy)benzene is compatible with a wide range of palladium- and nickel-catalyzed cross-coupling reactions, including Suzuki–Miyaura, Kumada, Negishi, and Buchwald–Hartwig couplings. The reactive C–Br bond undergoes efficient oxidative addition to Pd(0) and Ni(0) species under standard catalytic conditions.

How should 1-Bromo-4-(cyclohexyloxy)benzene be stored to maintain stability?

The compound should be stored in a tightly sealed container at room temperature, protected from light, moisture, strong oxidizers, and strong bases. Under these conditions, the compound is expected to remain stable for an extended period. Always refer to the current Aladdin Scientific SDS and certificate of analysis for lot-specific storage recommendations.

Can 1-Bromo-4-(cyclohexyloxy)benzene be used as a precursor in pharmaceutical synthesis?

Yes, the 4-(cyclohexyloxy)phenyl motif appears in various biologically active compounds and drug candidates. This compound can serve as a key intermediate for introducing the cyclohexyloxyphenyl fragment via cross-coupling or metal–halogen exchange chemistry. Researchers should validate purity requirements for their specific application using the certificate of analysis.

What is the molecular weight of 1-Bromo-4-(cyclohexyloxy)benzene?

The molecular weight of 1-Bromo-4-(cyclohexyloxy)benzene (C₁₂H₁₅BrO) is approximately 255.16 g/mol.

Is 1-Bromo-4-(cyclohexyloxy)benzene suitable for Grignard or organolithium preparations?

Yes, the aryl bromide can undergo metal–halogen exchange with n-BuLi or t-BuLi at low temperature (typically –78 °C) in dry THF or diethyl ether to generate the corresponding aryllithium reagent. Similarly, magnesium insertion under standard Grignard conditions can afford the corresponding arylmagnesium bromide, provided that moisture is rigorously excluded.

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. Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed.; Oxford University Press: Oxford, 2012.
4. Mitsunobu, O. The Use of Diethyl Azodicarboxylate and Triphenylphosphine in Synthesis and Transformation of Natural Products. Synthesis 1981, 1–28. doi:10.1055/s-1981-29317

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