4-Bromo-1-isopropyl-1H-imidazole: Properties & Applications
4-Bromo-1-isopropyl-1H-imidazole: Properties & Applications
4-Bromo-1-isopropyl-1H-imidazole is a halogenated, N-alkylated imidazole derivative widely valued as a versatile synthetic building block in medicinal chemistry, heterocyclic synthesis, and transition-metal-catalyzed cross-coupling reactions.
- Chemical Name
- 4-Bromo-1-isopropyl-1H-imidazole
- CAS Number
- Needs verification — see review flags
- Molecular Formula
- C₆H₉BrN₂
- Molecular Weight
- 189.05 g/mol (calculated)
- Key Functional Groups
- C-4 aryl bromide, N-1 isopropyl group, imidazole ring
- Primary Application
- Synthetic intermediate for heterocyclic and medicinal chemistry
- SKU
- B589690
Chemical Structure and Key Properties
4-Bromo-1-isopropyl-1H-imidazole belongs to the class of N-substituted bromoimidazoles. The imidazole ring is a five-membered aromatic heterocycle containing two nitrogen atoms at positions 1 and 3. In this compound, the N-1 nitrogen bears an isopropyl substituent, conferring enhanced lipophilicity and steric bulk relative to unsubstituted or N-methyl analogues. The bromine atom at C-4 serves as a highly reactive handle for further functionalization.
The aromatic character of the imidazole ring imparts planarity and π-electron delocalization, contributing to the compound's stability under standard laboratory storage conditions. The C–Br bond at the 4-position is well-suited for oxidative addition into palladium(0) and other transition-metal catalysts, making it an ideal electrophilic partner in cross-coupling reactions. The isopropyl group at N-1 prevents N–H tautomerism and eliminates ambiguity in regioselective reactions, which is a significant advantage over unprotected imidazoles.
Synthesis and Functionalization Strategies
The C-4 bromide of 4-Bromo-1-isopropyl-1H-imidazole can be leveraged in a broad range of transformations. Palladium-catalyzed cross-coupling reactions—including Suzuki–Miyaura, Negishi, Sonogashira, and Buchwald–Hartwig protocols—are among the most commonly employed methods to introduce aryl, vinyl, alkynyl, and amino substituents at the 4-position. These reactions typically proceed under mild conditions using commercially available palladium catalysts and appropriate bases.
The compound can also undergo lithium–halogen exchange at low temperatures (e.g., −78 °C with n-BuLi) to generate the corresponding C-4 lithiated species, which can then be quenched with a wide variety of electrophiles such as aldehydes, ketones, chlorosilanes, and carbon dioxide. Additionally, copper-mediated coupling and nucleophilic aromatic substitution routes may be applicable depending on the target structure. The N-1 isopropyl group remains stable under most of these conditions, ensuring regioselectivity throughout the synthetic sequence.
Applications in Medicinal and Agrochemical Research
Imidazole-containing scaffolds are prominent in drug discovery owing to the ring's ability to mimic histidine residues, coordinate metal ions in enzyme active sites, and engage in hydrogen-bonding interactions with biological targets. 4-Bromo-1-isopropyl-1H-imidazole serves as a key intermediate for the preparation of pharmacologically active imidazole derivatives, including kinase inhibitors, antifungal agents, and other bioactive heterocycles.
The N-isopropyl substitution pattern is particularly useful in medicinal chemistry because it can enhance metabolic stability and membrane permeability compared to smaller N-alkyl groups. Researchers synthesizing compound libraries for high-throughput screening (HTS) or structure–activity relationship (SAR) studies frequently employ this building block to introduce the 1-isopropylimidazol-4-yl pharmacophore into candidate molecules. In agrochemical research, bromoimidazole intermediates have been used in the development of fungicides and insecticides with heterocyclic cores.
Handling, Storage, and Safety Considerations
As with most organobromine heterocyclic intermediates, 4-Bromo-1-isopropyl-1H-imidazole should be handled with standard laboratory precautions. Researchers are advised to wear appropriate personal protective equipment (PPE), including nitrile gloves, safety glasses, and a laboratory coat. Operations that may generate dust or aerosols should be conducted in a well-ventilated fume hood.
The compound should be stored in a tightly sealed container, away from moisture, light, and incompatible materials such as strong oxidizers and strong bases. Cool, dry storage conditions (typically 2–8 °C or as specified on the product certificate of analysis) are recommended to maintain long-term stability. Users should consult the Safety Data Sheet (SDS) for complete hazard information, first-aid measures, and disposal guidance before use. Specific GHS hazard classifications and precautionary statements should be verified against the current SDS provided with the product (SKU B589690).
Frequently asked questions
What cross-coupling reactions is 4-Bromo-1-isopropyl-1H-imidazole compatible with?
The C-4 bromide is compatible with a range of palladium-catalyzed cross-coupling reactions, including Suzuki–Miyaura (with arylboronic acids), Negishi (with organozinc reagents), Sonogashira (with terminal alkynes), and Buchwald–Hartwig amination. Lithium–halogen exchange at −78 °C followed by electrophile quench is also a viable strategy for C-4 functionalization.
Why is the N-1 isopropyl group important in this building block?
The N-1 isopropyl group eliminates N–H tautomerism present in unprotected imidazoles, ensuring regioselective reactivity at C-4. It also increases the lipophilicity and can improve metabolic stability of derived compounds, making it a strategically valuable substituent in medicinal chemistry programs.
How should 4-Bromo-1-isopropyl-1H-imidazole (SKU B589690) be stored to ensure stability?
The compound should be stored in a tightly sealed container under cool, dry conditions, away from moisture, light, and strong oxidizing agents. Storage at 2–8 °C is generally recommended for halogenated heterocyclic intermediates; consult the product certificate of analysis and SDS for specific requirements for this lot.
Is 4-Bromo-1-isopropyl-1H-imidazole used in drug discovery?
Yes. The 1-isopropylimidazol-4-yl pharmacophore is incorporated into a range of biologically active molecules, including kinase inhibitors and antifungal candidates. The compound serves as a key intermediate for SAR studies and compound-library synthesis where the imidazole scaffold is required.
References
- Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed.; Oxford University Press: Oxford, 2012. (General reference for imidazole chemistry and cross-coupling reactions.)
- Küenburg, B.; Czollner, L.; Bracher, F.; Jordis, U. Development of a Pilot-Scale Process for the Anti-Alzheimer Drug (−)-Galanthamine Using Large-Scale Pd-Catalyzed Reactions and Imidazole Chemistry. Org. Process Res. Dev. 1999, 3, 425–431. (Cited as a general example of palladium-catalyzed imidazole functionalization; relevance to this specific compound needs verification.) doi:10.1021/op990026a
- Aladdin Scientific Product Page: 4-Bromo-1-isopropyl-1H-imidazole, SKU B589690. (Primary source for product identity and availability.)
Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.
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