(S)-tert-butyl 2-(6-bromo-1H-benzo[d]imidazol-2-yl)pyrrolidine-1-carboxylate
[CAS# 1208007-67-3]

Identification

• Classification: Organic raw materials >> Carboxylic compounds and derivatives >> Carboxylic esters and their derivatives
• Name: (S)-tert-butyl 2-(6-bromo-1H-benzo[d]imidazol-2-yl)pyrrolidine-1-carboxylate
• Synonyms: tert-butyl (2S)-2-(6-bromo-1H-benzimidazol-2-yl)pyrrolidine-1-carboxylate
• Molecular Formula: C₁₆H₂₀BrN₃O₂
• Molecular Weight: 366.25
• CAS Registry Number: 1208007-67-3
• SMILES: CC(C)(C)OC(=O)N1CCC[C@H]1C2=NC3=C(N2)C=C(C=C3)Br

Properties

• Density: 1.4±0.1 g/cm³ Calc.^*
• Boiling point: 528.6±40.0 ºC 760 mmHg (Calc.)^*
• Flash point: 273.5±27.3 ºC (Calc.)^*
• Index of refraction: 1.624 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H315-H319
• Precautionary Statements: P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313

Discovory and Applicatios

(S)-tert-butyl 2-(6-bromo-1H-benzo[d]imidazol-2-yl)pyrrolidine-1-carboxylate is a chiral heterocyclic compound widely used in synthetic organic chemistry as an intermediate for constructing complex molecules, particularly those with pharmaceutical or catalytic significance. It features a benzimidazole ring substituted at the 6-position with a bromine atom, a stereocontrolled pyrrolidine moiety, and a tert-butoxycarbonyl (Boc) protecting group on the nitrogen of the pyrrolidine ring.

The discovery and use of benzimidazole derivatives trace back to early studies in medicinal chemistry, where the benzimidazole scaffold was recognized for its structural resemblance to purines. This resemblance has allowed benzimidazole compounds to serve as bioisosteres in numerous drug design efforts. The benzimidazole core in this compound is modified with a bromine atom at the 6-position, making it a reactive site for further derivatization via electrophilic aromatic substitution or cross-coupling reactions. The 6-bromo substituent is particularly useful for facilitating palladium-catalyzed transformations, including Suzuki, Stille, and Buchwald–Hartwig couplings, to append various aryl or heteroaryl groups under controlled conditions.

The (S)-configured pyrrolidine ring is a five-membered nitrogen-containing heterocycle, a structural motif that appears in many natural products and therapeutic agents. The stereochemistry is of particular importance, as it often influences the compound’s pharmacodynamic and pharmacokinetic profiles. Enantiomerically enriched pyrrolidine derivatives are frequently found in drugs acting as enzyme inhibitors, neurotransmitter modulators, and receptor agonists or antagonists. The stereoselective incorporation of the (S)-pyrrolidine unit into this molecule suggests its application in the development of enantioselective ligands or as an intermediate for active pharmaceutical ingredients.

The Boc (tert-butoxycarbonyl) group attached to the nitrogen atom of the pyrrolidine serves as a protecting group, allowing selective reactions to be performed on other parts of the molecule while maintaining the integrity of the nitrogen center. The Boc group is acid-labile and can be removed under mild acidic conditions such as treatment with trifluoroacetic acid. This feature enables stepwise synthetic elaboration in multi-step synthetic sequences, which is advantageous in medicinal chemistry and peptide synthesis.

Applications of (S)-tert-butyl 2-(6-bromo-1H-benzo[d]imidazol-2-yl)pyrrolidine-1-carboxylate are primarily in synthetic organic chemistry. Its structure enables use in the preparation of chiral ligands for asymmetric catalysis, especially those designed to coordinate with transition metals through the nitrogen atoms of the benzimidazole and pyrrolidine. These ligands have been employed in enantioselective transformations such as asymmetric hydrogenations and allylic substitutions. Furthermore, the compound may serve as a precursor to benzimidazole-based drugs and materials with antimicrobial, antiviral, and anticancer properties, as the benzimidazole ring system is a common pharmacophore in medicinal chemistry.

The synthesis of this compound typically begins with the formation of the benzimidazole core, followed by bromination at the 6-position using reagents like N-bromosuccinimide. The chiral pyrrolidine ring is introduced via nucleophilic substitution or coupling reactions, ensuring retention of stereochemical configuration. The nitrogen of the pyrrolidine is then protected with a Boc group to allow for subsequent selective chemistry. Overall, the synthetic route is designed to provide high enantiomeric purity and yield, making the compound suitable for applications in research and development.

The compound is generally a crystalline solid with good solubility in organic solvents such as dichloromethane, ethyl acetate, and dimethylformamide. It should be stored in a dry, inert atmosphere to prevent degradation, particularly of the Boc group, which can hydrolyze under moist conditions. As with all brominated aromatic compounds and nitrogen-containing heterocycles, appropriate safety precautions should be observed, including the use of gloves, protective eyewear, and a fume hood.

In conclusion, (S)-tert-butyl 2-(6-bromo-1H-benzo[d]imidazol-2-yl)pyrrolidine-1-carboxylate is a versatile chiral intermediate with applications in asymmetric catalysis, drug discovery, and the synthesis of complex organic molecules. Its combination of reactive functionality and controlled stereochemistry makes it a valuable tool in the advancement of chemical synthesis.