375857-65-1 | 3-Bromo-7-(trifluoromethyl)imidazo[1,2-a]pyrimidine

CAS:375857-65-1 | 3-Bromo-7-(trifluoromethyl)imidazo[1,2-a]pyrimidine,Description

3-Bromo-7-(trifluoromethyl)imidazo[1,2-a]pyrimidine is a chemical compound that serves as a key intermediate in the synthesis of various heterocyclic compounds. This compound is characterized by the presence of a bromine atom at the third position and a trifluoromethyl group at the seventh position on the imidazo[1,2-a]pyrimidine ring system. The imidazo[1,2-a]pyrimidine scaffold is a prominent feature in many pharmacologically active molecules and is of significant interest in medicinal chemistry due to its potential biological activities.

Synthesis Analysis

The synthesis of 3-Bromo-7-(trifluoromethyl)imidazo[1,2-a]pyrimidine derivatives has been achieved through various methods. One approach involves the copper-mediated aerobic oxidative coupling of pyridines and enamides, which tolerates a wide range of functional groups and proceeds under mild conditions. Another method described the solid-phase synthesis of imidazo[1,2-a]pyrimidine derivatives by condensation between an α-bromoketone bound to solid support and various 2-aminopyrimidine derivatives. Additionally, the synthesis of imidazo[1,2-a]pyrimidine derivatives from 2-aminopyrimidines, methyl aryl ketones, and halogens, particularly bromine, has been reported, leading to the formation of bromo-substituted compounds.

Molecular Structure Analysis

The molecular structure of 3-Bromo-7-(trifluoromethyl)imidazo[1,2-a]pyrimidine is characterized by the imidazo[1,2-a]pyrimidine core, which is a fused heterocyclic system combining imidazole and pyrimidine rings. The presence of the bromine atom and the trifluoromethyl group on this core structure allows for further functionalization through various chemical reactions, making it a versatile intermediate for the synthesis of more complex molecules.

Chemical Reactions Analysis

The bromine atom in 3-Bromo-7-(trifluoromethyl)imidazo[1,2-a]pyrimidine is a reactive site that can undergo nucleophilic aromatic substitution (SNAr) reactions. For instance, the C-5 position can be functionalized by activating the C–O bond of the lactam function, followed by the addition of amine or thiol to yield monosubstituted derivatives. Arylation at the C-3 position can be performed via Suzuki–Miyaura cross-coupling using aromatic and heteroaromatic boronic acids. Furthermore, the compound can participate in Michael addition/intramolecular cyclization reactions for the synthesis of fluoromethylated imidazo[1,2-a]pyrimidines.

Physical and Chemical Properties Analysis

The physical and chemical properties of 3-Bromo-7-(trifluoromethyl)imidazo[1,2-a]pyrimidine are influenced by the electron-withdrawing effects of the bromine and trifluoromethyl groups. These substituents can affect the electron density of the heterocyclic core, potentially impacting the reactivity and stability of the compound. The presence of these groups also allows for the introduction of additional functional groups through various chemical reactions, which can be tailored to produce compounds with desired physical and chemical properties for potential applications in drug discovery and development.

Scientific Research Applications

Synthesis and Characterization

• Palladium-Catalyzed Arylation : Imidazo[1,2-a]pyrimidines, including 3-bromo-7-(trifluoromethyl)imidazo[1,2-a]pyrimidine, can be arylated at the 3-position using aryl bromides, base, and a catalytic amount of palladium. This method offers an efficient one-step synthesis approach from unsubstituted heterocycles (Li et al., 2003).
• Synthesis of Derivatives : The compound and its derivatives can be synthesized by reacting 2-aminopyrimidines with methyl aryl ketones and halogens, leading to various substituted 2-arylimidazo[1,2-a]pyrimidines (Kochergin et al., 2000).

Applications in Chemistry

• Anti-corrosion Activity : Heterocyclic compounds containing imidazo[1,2-a]pyrimidine moiety, synthesized through a series of reactions, have shown potential for anti-corrosion applications (Rehan et al., 2021).
• Solid-Phase Synthesis : Imidazo[1,2-a]pyrimidines can be synthesized on a solid support, which is significant for the development of pharmaceutical compounds and for streamlining chemical synthesis processes (Kazzouli et al., 2003).
• Fluorescent Properties : Certain derivatives of imidazo[1,2-a]pyrimidine exhibit fluorescent properties, which can be harnessed in the development of biomarkers and photochemical sensors (Velázquez-Olvera et al., 2012) .

Future Directions

The serious ecological problems nowadays provoke scientists to search environmentally benign synthetic strategies as much as possible. This will likely influence future research directions in the synthesis of imidazo[1,2-a]pyridines and related compounds.

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