2,4-Dimethoxybromobenzene

    2,4-Dimethoxybromobenzene, systematically named 1-Bromo-2,4-dimethoxybenzene, has a CAS number of 17715-69-4, a molecular formula of C₈H₉BrO₂, and a molecular weight of 217.06 g/mol. This compound typically appears as a colorless to pale yellow liquid or low-melting-point solid. It has a melting point of 25-26°C, a boiling point of 153-155°C at 18 mmHg, and a density of 1.507 g/mL.

    The molecule consists of a benzene ring skeleton with a bromine atom at the 1-position and two methoxy groups (-OCH₃) at the 2- and 4-positions. This specific substitution pattern imparts unique chemical properties to the compound. Both methoxy groups are electron-donating substituents that provide electron density to the benzene ring through both resonance and inductive effects, thereby activating the ring toward electrophilic aromatic substitution reactions. Meanwhile, the bromine atom serves as an excellent leaving group that can be substituted by various nucleophiles in cross-coupling reactions.

    The compound has an XLogP3 value of approximately 2.5, indicating moderate lipophilicity, which influences its solubility behavior in organic solvents. The molecule contains two hydrogen bond acceptors (from the oxygen atoms of the two methoxy groups), zero hydrogen bond donors, and two rotatable bonds. The topological polar surface area is 18.46 Ų. At room temperature, the compound exists as a liquid but solidifies into a crystalline solid below 25°C.

    Catalytic Bromination: Using N-bromosuccinimide in the presence of a catalyst allows for selective bromination under relatively mild conditions, yielding high-purity product.This compound participates in several important organic transformations: Suzuki-Miyaura Cross-Coupling: In the presence of a palladium catalyst and a base, the bromine atom undergoes cross-coupling with aryl or alkyl boronic acids to generate biaryl compounds. This is one of the most important applications of this compound.Buchwald-Hartwig Amination: The bromine atom reacts with primary or secondary amines under palladium catalysis to form carbon-nitrogen bonds, producing aniline derivatives.

    Miyaura Borylation: Under palladium catalysis with bis(pinacolato)diboron, the bromine is converted to a boronic ester, providing a more flexible synthetic strategy for subsequent coupling reactions.Sonogashira Coupling: Reaction with terminal alkynes under palladium/copper co-catalysis yields arylalkyne compounds.

    Pharmaceutical Intermediate: This compound serves as an important intermediate for synthesizing various drug molecules. Methoxy groups are commonly used in medicinal chemistry to modulate lipophilicity, metabolic stability, and bioavailability of drug candidates. The bromine atom provides a convenient site for subsequent functional group transformations.

    Agrochemicals: It can be used as an intermediate for synthesizing insecticides, herbicides, and fungicides. The presence of two methoxy groups helps enhance biological activity. Organic Materials: It serves as a building block in the synthesis of organic light-emitting diodes, liquid crystal materials, and conductive polymers. Chemical Reagent: As a common organic synthesis building block in laboratories, it is used to construct various aryl ether compounds.

    This compound should be stored in a cool, dry, well-ventilated area away from ignition sources and oxidizing agents. Since it is a liquid at room temperature, it is recommended to store it in sealed containers to prevent volatilization. Appropriate personal protective equipment should be worn during handling, including protective gloves, safety goggles, and a lab coat. Avoid contact with skin and eyes.

    2,4-Dimethoxybromobenzene, as an important aryl bromide, plays a significant role in organic synthesis, pharmaceutical development, and materials science due to its unique chemical structure  and reactivity. The combination of two electron-donating methoxy groups and a reactive bromine atom makes it an ideal starting material for constructing complex molecular frameworks.