Methyl 6 bromo 2 naphthoate uses

Methyl 6-bromo-2-naphthoate is commonly used in the synthesis of adapalene, a retinoid targeting RARβ and RARγ receptors. While there is no direct association with specific natural substances, it can be synthesized in the laboratory. Research on this compound mainly focuses on its potential applications in organic synthesis as a precursor for constructing more complex molecules. After an aromatic Finkelstein reaction, methyl 6-bromo-2-naphthoate can be hydrolyzed to yield 6-iodo-2-naphthoic acid. The structure of methyl 6-bromo-2-naphthoate is as follows:

Methyl 6 bromo 2 naphthoate uses

Methyl 6 bromo 2 naphthoate uses in Chemical

Methyl 6-bromo-2-naphthoate serves as a multifunctional precursor for various organic compounds. The bromine atom is a reactive site prone to substitution reactions, allowing the introduction of different functional groups. This feature makes it a valuable starting material for constructing complex molecules.

Methyl 6-bromo-2-naphthoate can be used to synthesize:

• 6-vinyl-2-naphthaldehyde.
• 6-[3-tert-butyl-4-[(tert-butyl)ethoxy]phenyl]-2-naphthoate.
• 6-(3-tert-butyl-4-methoxyphenyl)-2-naphthoate.
• 6-[3-(1-adamantyl)-4-[[(2,3-dimethyl-1,3-dioxane-4-yl)methoxy]phenyl]-2-naphthoate.
• 2-bromo-6-(bromomethyl)naphthalene.

Zong Xinjie and others used methyl 6-bromo-2-naphthoate and hydrazine hydrate to synthesize 6-bromo-2-naphthoyl hydrazone, which was then reacted with halogenated benzaldehydes to produce three new types of dihalonaphthoylhydrazones (C18H12BrXN2O, X=F, Cl, Br). X-ray crystallography revealed that these three hydrazones belong to the monoclinic system, P21 space group. All three hydrazones showed high thermal stability with decomposition temperatures exceeding 330°C. Fluorescence spectra indicated that each hydrazone formed a complex with bovine serum albumin (BSA) via static quenching, with binding constants (KA) around 10⁵ L·mol^-1, indicating strong binding ability.

Methyl 6 bromo 2 naphthoate uses in Pharmaceutical

Methyl 6-bromo-2-naphthoate can be used as an intermediate for synthesizing candidate drugs with desired pharmacological properties.

Synthesis of Adapalene

Methyl 6-bromo-2-naphthoate is a key intermediate in the synthesis of adapalene. Liu Ying and others used bromophenol and adamantanol as starting materials to obtain 2-(1-adamantyl)-4-bromophenol (4) under sulfuric acid and glacial acetic acid catalysis; compound (4) was methylated with dimethyl sulfate to form 2-(1-adamantyl)-4-bromobenzyl ether (5); compound (5) was reacted with methyl 6-bromo-2-naphthoate to yield 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoate (7); compound (7) was saponified under lithium hydroxide to obtain adapalene (1). The total yield for the four-step reaction was 71.1%.

In Liu Zhichang and others' report, 1-adamantanol and 4-bromophenol were reacted through the Fukuyama reaction and phenolic hydroxyl methylation to obtain 2-(1-adamantyl)-4-bromobenzyl ether. This was then cross-coupled with methyl 6-bromo-2-naphthoate using bimetallic catalysis, followed by saponification to produce adapalene with a total yield of 67%.

Synthesis of Dasabuvir

Qian Ping and others used ortho-tert-butylphenol as the starting material, which underwent halogenation, methylation, and Ullmann coupling to produce the key intermediate 1-(3-tert-butyl-5-iodo-4-methoxyphenyl) pyrimidine-2,4-(1H,3H)-dione (5). Methyl 6-bromo-2-naphthoate was used as the starting material, which underwent hydrolysis, Curtis rearrangement, sulfonylation, and substitution reactions to produce the intermediate N-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl)naphthalene-2-yl)methanesulfonamide (9). Intermediate 5 was then coupled with intermediate 9 via Suzuki coupling to obtain dasabuvir.

Research and Development

Beyond specific applications, methyl 6-bromo-2-naphthoate is a valuable tool in chemical research. Its reactive and structural features make it suitable for studying reaction mechanisms, developing new synthetic methods, and exploring structure-activity relationships in various chemical contexts.

Benefits of Using Methyl 6-Bromo-2-Naphthoate

High Purity

Methyl 6-bromo-2-naphthoate boasts a purity of up to 98%, a critical factor in chemical reactions. This high purity ensures consistency and reliability, minimizing the impact of impurities on reaction outcomes. Contaminants often interfere with desired chemical pathways, leading to reduced yields or unwanted by-products. Using high-purity starting materials like methyl 6-bromo-2-naphthoate can enhance the reproducibility and efficiency of synthesis processes.

Reaction Efficiency

The chemical properties of methyl 6-bromo-2-naphthoate significantly impact its reaction efficiency. Particularly, the bromine atom acts as a multifunctional functional group, participating in various transformations. Its electrophilic nature makes it susceptible to nucleophilic attack, allowing for the introduction of diverse substituents onto the naphthalene core. Additionally, the ester functional group provides opportunities for further modifications, such as hydrolysis or reduction, expanding the possibilities for synthesis. These combined properties make methyl 6-bromo-2-naphthoate a valuable cornerstone in constructing complex molecules.

Versatility

Methyl 6-bromo-2-naphthoate exhibits exceptional versatility in chemical synthesis. Its adaptability is evident in its role as a precursor for various compounds, including pharmaceuticals, dyes, and materials. The bromine atom can be selectively functionalized to introduce different groups, while the ester part can be manipulated to produce various derivatives. This flexibility enables chemists to tailor molecules according to specific needs, making it an indispensable tool in synthetic chemistry.

Handling and Safety Information for Methyl 6-Bromo-2-Naphthoate

Proper Storage Conditions

Proper storage is crucial for maintaining the stability of the compound and preventing degradation. Exposure to high temperatures, moisture, or light can accelerate decomposition. It is recommended to store this chemical in a sealed container away from incompatible substances.

Safety Precautions

As with any chemical, appropriate personal protective equipment should be worn, including gloves, goggles, and laboratory coats. Adequate ventilation is essential to minimize vapor exposure. Avoid contact with skin and eyes, and do not ingest the compound. In case of accidental contact, rinse the affected area with plenty of water and seek medical attention if necessary.

References

• Zong Xinjie, Liu Xiangrong, Zhao Shunsheng, et al. Synthesis, Crystal Structure, and Interaction with BSA and ct-DNA of Dihalogenated Naph thoylhydrazones [J]. Chemical Research and Application, 2018, 30(4): 542-549. DOI:10.3969/j.issn.1004-1656.2018.04.014.
• Liu Ying, Ma Xiaohua, Yang Xianhua, et al. Synthesis of Adapalene [J]. Journal of Xinyang Normal University (Natural Science Edition), 2007, 20(4): 472-474. DOI:10.3969/j.issn.1003-0972.2007.04.028.
• Liu Zhichang, Long Bohua, Zheng Donghui, et al. Synthesis of Adapalene via Bimetallic Catalyzed Cross-Coupling Reaction [J]. China Medical Industry Journal, 2006, 37(4): 219-220. DOI:10.3969/j.issn.1001-8255.2006.04.002.
• Qian Ping, Xia Juanjuan, Du Xinming, et al. Research on the Synthesis Process of Dasabuvir [J]. Chinese Journal of Medicinal Chemistry, 2016, 26(5): 375-379. DOI:10.14142/j.cnki.cn21-1313/r.2016.05.004.
• Charpentier B, Bernardon J M, Eustache J, et al. Synthesis, Structure-Affinity Relationships, and Biological Activities of Ligands Binding to Retinoic Acid Receptor Subtypes [J]. Journal of Medicinal Chemistry, 1995, 38(26): 4993-5006.
• Silvestri F, García-Iglesias M, Yum J H, et al. Carboxy-1, 4-phenylenevinylene-and Carboxy-2, 6-naphthylene-vinylene Unsymmetrical Substituted Zinc Phthalocyanines for Dye-Sensitized Solar Cells [J]. Journal of Porphyrins and Phthalocyanines, 2009, 13(03): 369-375.