1-(4-Bromophenyl)pyrrolidine: Properties, Handling & Lab Use

1-(4-Bromophenyl)pyrrolidine is a versatile aryl bromide building block widely employed in palladium-catalyzed cross-coupling reactions and medicinal chemistry programs as a source of the electron-rich 4-(pyrrolidin-1-yl)phenyl motif.

CAS Number

50777-97-4

Molecular Formula

C₁₀H₁₂BrN

Molecular Weight

226.11 g/mol

Appearance

Pale yellow to off-white solid or low-melting solid

Key Functional Groups

Aryl bromide, tertiary amine (pyrrolidine)

Primary Application

Cross-coupling substrate and synthetic intermediate in organic and medicinal chemistry

Storage Condition

Sealed, cool, dry, and dark place; protect from moisture

Chemical Identity and Structural Features

1-(4-Bromophenyl)pyrrolidine (CAS 50777-97-4) consists of a pyrrolidine ring attached at its nitrogen to the para position of a bromobenzene ring. The molecular formula is C₁₀H₁₂BrN with a molecular weight of approximately 226.11 g/mol. The compound features two complementary reactive handles: (1) the aryl C–Br bond, which is an excellent electrophilic partner for transition-metal-catalyzed cross-coupling reactions such as Suzuki–Miyaura, Buchwald–Hartwig, and Kumada couplings; and (2) the tertiary pyrrolidine nitrogen, which imparts significant electron-donating character to the arene via resonance, raising the electron density at the ortho and para positions of the ring. This electronic activation distinguishes it from simple aryl bromides and can influence both the reactivity of the C–Br bond toward oxidative addition and the physicochemical properties (e.g., lipophilicity, basicity) of derived intermediates and products. The absence of N–H functionality means the compound is less prone to oxidative degradation pathways associated with secondary amines.

Synthetic Applications and Role as a Building Block

The aryl bromide handle of 1-(4-Bromophenyl)pyrrolidine makes it a broadly useful electrophilic partner in a range of transition-metal-catalyzed transformations commonly employed in modern drug discovery and materials science programs:

• Suzuki–Miyaura coupling: Reacts with aryl- or heteroarylboronic acids/esters in the presence of a Pd catalyst and base to furnish biaryls bearing the electron-donating 4-(pyrrolidinyl)phenyl group.
• Buchwald–Hartwig amination: The C–Br bond can undergo Pd-catalyzed C–N bond formation with primary or secondary amines, enabling rapid assembly of diarylamine scaffolds.
• Negishi and Kumada coupling: Compatible with organozinc and Grignard reagents for C–C bond construction under Pd or Ni catalysis.
• Directed C–H functionalization: The electron-rich arene can participate in directed or undirected C–H activation sequences when combined with appropriate directing groups or catalysts.
• Medicinal chemistry: The pyrrolidinyl-phenyl motif is a recurring pharmacophore in CNS-active compounds and kinase inhibitors; this building block enables efficient SAR exploration around such scaffolds.

Researchers should note that the electron-donating pyrrolidine group may moderate the rate of oxidative addition compared with electron-neutral or electron-poor aryl bromides, and catalyst/ligand selection should be optimized accordingly.

Safe Handling, Storage, and Disposal

Hazard overview: 1-(4-Bromophenyl)pyrrolidine is an organic amine-containing aryl bromide. In the absence of a published Safety Data Sheet (SDS) for this specific compound in the source material, researchers should apply standard precautionary principles applicable to reactive aryl bromides and tertiary amines. Always consult the supplier SDS before use.

Personal protective equipment (PPE): Wear chemical-splash safety goggles, nitrile gloves, and a laboratory coat. Work in a well-ventilated fume hood, particularly when weighing or handling the neat compound, to minimize inhalation of dust or vapors.

Storage: Store in a tightly sealed container in a cool (15–25 °C), dry, and dark location away from strong oxidizers and moisture. Do not store with strong acids or oxidizing agents. Under appropriate conditions the compound is expected to be stable for an extended period; however, periodic purity checks by TLC, HPLC, or NMR are advisable.

Spill management: Contain spills with inert absorbent material (e.g., vermiculite or dry sand). Avoid generating dust. Collect and transfer to a sealed, labeled waste container. Wash affected surfaces with water followed by appropriate detergent.

Disposal: Dispose of in accordance with local, regional, and national regulations for chemical waste. Do not discharge to drains, waterways, or the environment.

Quality, Purity, and Analytical Verification

For research applications, particularly those in medicinal chemistry and process chemistry, verifying the identity and purity of 1-(4-Bromophenyl)pyrrolidine before use is strongly recommended. The following analytical techniques are commonly applied:

• ¹H NMR spectroscopy: Characteristic signals include aromatic protons appearing as an AA'BB' system (two doublets) in the 7.1–7.4 ppm region, and aliphatic pyrrolidine CH₂ protons at approximately 1.9–2.0 ppm (β-CH₂) and 3.2–3.3 ppm (α-CH₂ adjacent to nitrogen). Exact shifts may vary with solvent.
• ¹³C NMR spectroscopy: Expected signals for the ipso carbons bearing the nitrogen substituent and the bromide, aromatic CH carbons, and aliphatic ring carbons provide a diagnostic fingerprint.
• HPLC (reverse-phase): Purity assessment ≥95% (area%) is typical for research-grade material. LC-MS can simultaneously confirm molecular weight (expected [M+H]⁺ at m/z 226/228 reflecting the ⁷⁹Br/⁸¹Br isotope pattern).
• Melting point: Verification against literature or certificate-of-analysis (CoA) values confirms identity and detects gross impurities.
• Karl Fischer titration: If moisture-sensitive downstream reactions (e.g., organolithium chemistry) are planned, water content determination is advisable.

Always request and review the Certificate of Analysis (CoA) from Aladdin Scientific prior to use. Contact technical support if purity or identity does not meet experimental requirements.

Frequently asked questions

What transition-metal-catalyzed reactions is 1-(4-Bromophenyl)pyrrolidine suitable for?

1-(4-Bromophenyl)pyrrolidine is well-suited as an electrophilic coupling partner in Suzuki–Miyaura, Buchwald–Hartwig, Negishi, and Kumada cross-coupling reactions owing to its reactive aryl C–Br bond. The electron-donating pyrrolidine group should be taken into account when selecting the palladium catalyst and phosphine ligand system, as it influences the rate of oxidative addition.

How should 1-(4-Bromophenyl)pyrrolidine be stored to maintain stability?

The compound should be stored in a tightly sealed container under cool (15–25 °C), dry, and dark conditions, away from moisture and strong oxidizers. Periodic purity verification by HPLC or NMR is advisable for long-term stocks to ensure the material remains fit for purpose.

How can I confirm the identity and purity of the compound before use?

Review the Certificate of Analysis (CoA) supplied by Aladdin Scientific for lot-specific purity data. Independent verification can be achieved by ¹H NMR (checking the characteristic aromatic AA'BB' pattern and pyrrolidine CH₂ signals) and reverse-phase HPLC purity determination. LC-MS confirmation of the [M+H]⁺ isotope pattern at m/z 226/228 is a rapid and reliable identity check.

Is 1-(4-Bromophenyl)pyrrolidine air- and moisture-sensitive?

As a tertiary arylamine, 1-(4-Bromophenyl)pyrrolidine is generally more stable to air and moisture than primary or secondary aryl amines. Nevertheless, it is good laboratory practice to store the compound sealed and dry, and to handle it in a fume hood. For highly sensitive downstream reactions, use of inert atmosphere (N₂ or Ar) techniques is recommended.

What personal protective equipment is recommended when handling this compound?

Researchers should wear chemical-splash safety goggles, nitrile gloves, and a laboratory coat as a minimum. All weighing and manipulation of the neat compound should be performed in a well-ventilated fume hood. Consult the supplier SDS for comprehensive hazard and first-aid information before beginning work.

References

1. Miyaura, N.; Suzuki, A. Palladium-Catalyzed Cross-Coupling Reactions of Organoboron Compounds. Chem. Rev. 1995, 95, 2457–2483. doi:10.1021/cr00039a007
2. Hartwig, J. F. Evolution of a Fourth Generation Catalyst for the Amination and Thioetherification of Aryl Halides. Acc. Chem. Res. 2008, 41, 1534–1544. doi:10.1021/ar800098p
3. Aladdin Scientific. Product Certificate of Analysis: 1-(4-Bromophenyl)pyrrolidine, SKU B151811. Aladdin Scientific, Shanghai.

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