4-Bromo-1-butene: Properties, Synthesis & Lab Applications

4-Bromo-1-butene is a bifunctional homoallylic alkyl bromide widely employed as a versatile synthetic building block in organic chemistry, enabling alkylation, cyclization, and cross-coupling reactions through its reactive terminal alkene and primary C–Br bond.

CAS Number

5162-44-7

Molecular Formula

C₄H₇Br

Molecular Weight

135.00 g/mol

Appearance

Colorless to pale yellow liquid

Boiling Point

~98–100 °C at 760 mmHg

Functional Groups

Terminal alkene (vinyl) and primary alkyl bromide

Key Reactivity

Nucleophilic substitution (SN2), Grignard formation, ring-closing metathesis, radical reactions

Chemical Identity and Physical Properties

4-Bromo-1-butene (CAS 5162-44-7) is a four-carbon homoallylic bromide with the molecular formula C₄H₇Br and a molecular weight of approximately 135.00 g/mol. Its structure features a terminal vinyl group (CH₂=CH–) at C-1 and a primary C–Br bond at C-4, making it a bifunctional molecule capable of independent reactivity at each end.

The compound is a colorless to pale yellow liquid at room temperature with a boiling point of approximately 98–100 °C at atmospheric pressure. It is miscible with common organic solvents such as diethyl ether, tetrahydrofuran (THF), dichloromethane, and toluene, but essentially immiscible with water. Its density is reported to be approximately 1.33 g/mL at 25 °C. Like other primary alkyl bromides, it is moisture-sensitive and should be stored under inert atmosphere at low temperature (2–8 °C) to prevent decomposition or hydrolysis.

Reactivity and Key Reactions

The dual functionality of 4-Bromo-1-butene makes it an exceptionally versatile reagent in synthetic organic chemistry. The primary C–Br bond is highly susceptible to SN2 substitution, allowing efficient alkylation of a broad range of nucleophiles including amines, thiols, alcohols (as alkoxides), carbanions (enolates, organolithiums), and cyanide.

Grignard and Organolithium Formation: Treatment of 4-Bromo-1-butene with magnesium turnings in anhydrous THF or diethyl ether affords the corresponding homoallylic Grignard reagent (3-butenylmagnesium bromide), a widely used nucleophile for chain elongation and addition to carbonyl compounds. Care must be taken to avoid Wurtz coupling side reactions.

Ring-Closing Metathesis (RCM) Precursors: The terminal alkene of 4-Bromo-1-butene can be incorporated into diene substrates after initial alkylation, subsequently enabling ring-closing olefin metathesis with Grubbs-type catalysts to construct five- and six-membered carbocyclic and heterocyclic rings.

Radical and Transition-Metal-Catalyzed Reactions: Under radical conditions, the allylic position and the C–Br bond both participate in chain-propagation steps. Palladium-catalyzed cross-coupling (e.g., Suzuki, Negishi, Heck) can also be applied to install aryl or vinyl groups onto the carbon skeleton.

Cyclization: Intramolecular reactions exploiting both functional groups enable synthesis of cyclobutane, cyclopentane, and lactam/lactone ring systems, making this reagent valuable in target-oriented synthesis of natural products and pharmaceuticals.

Applications in Organic Synthesis

4-Bromo-1-butene serves as a key building block across numerous areas of synthetic chemistry:

• Natural Product Synthesis: The homoallylic bromide unit is a recurrent structural motif in terpenoid, alkaloid, and polyketide natural products. Researchers use 4-Bromo-1-butene to introduce the butenyl side chain or as the electrophilic partner in fragment coupling strategies.
• Pharmaceutical Intermediates: The compound is employed in the preparation of drug candidates and active pharmaceutical ingredients (APIs) requiring a four-carbon tether with an olefinic handle for further diversification (e.g., via oxidation, dihydroxylation, epoxidation, or hydroformylation).
• Polymer and Material Science: As a chain-transfer agent or co-monomer, 4-Bromo-1-butene can be incorporated into polymer backbones, enabling post-polymerization functionalization via the residual bromide.
• Bioconjugation and Probe Chemistry: The electrophilic bromide enables conjugation to biomolecule nucleophiles (e.g., cysteine thiols, lysine amines), while the alkene provides a handle for thiol–ene click chemistry or cross-metathesis labeling.

Safe Handling, Storage, and Regulatory Considerations

Hazard Profile: 4-Bromo-1-butene is a flammable liquid and an irritant. It may cause skin, eye, and respiratory tract irritation upon contact or inhalation. As a primary alkyl bromide, it is a potential alkylating agent; prolonged or repeated exposure should be avoided. Appropriate personal protective equipment (PPE) — including nitrile gloves, safety goggles, and a lab coat — must be worn at all times when handling this compound.

Ventilation: All operations should be conducted in a well-ventilated fume hood to minimize vapor inhalation. The vapor density is greater than air; ensure low-lying areas are adequately ventilated.

Storage: Store in a tightly sealed container under inert gas (nitrogen or argon) at 2–8 °C, away from heat, ignition sources, oxidizers, and strong bases. Refrigerated storage slows polymerization of the vinyl group and hydrolysis of the C–Br bond.

Disposal: Dispose of waste material in accordance with local, national, and institutional regulations for halogenated organic solvents. Do not pour down the drain.

Regulatory Status: Users should consult the current Safety Data Sheet (SDS) supplied with the product for up-to-date GHS classifications, transport information (UN number, packing group), and jurisdiction-specific requirements.

Frequently asked questions

What nucleophiles react efficiently with 4-Bromo-1-butene via SN2?

The primary C–Br bond in 4-Bromo-1-butene undergoes efficient SN2 substitution with a wide range of nucleophiles, including sodium or potassium alkoxides, thiolates, primary and secondary amines, malonate enolates, cyanide (to give the nitrile), azide, and organocuprates. Reactions are typically run in polar aprotic solvents such as DMF, DMSO, or acetonitrile at 0 °C to room temperature.

How should 4-Bromo-1-butene be stored to maximize shelf life?

4-Bromo-1-butene should be stored in a tightly sealed, amber glass container under an inert atmosphere (nitrogen or argon) at 2–8 °C. These conditions retard both vinyl group polymerization and hydrolysis of the alkyl bromide. Avoid exposure to light, moisture, heat, and strong oxidizers. Always inspect for discoloration before use, as a darkening color may indicate degradation.

Can 4-Bromo-1-butene be used directly in Grignard reactions?

Yes. 4-Bromo-1-butene reacts with magnesium turnings in anhydrous THF or diethyl ether to form 3-butenylmagnesium bromide, a homoallylic Grignard reagent. Activation of the magnesium (e.g., with iodine or 1,2-dibromoethane) is often recommended to initiate the reaction. The internal alkene remains largely intact under standard Grignard conditions, though competing Wurtz coupling can be minimized by slow addition and controlled temperature.

What is the difference between 4-Bromo-1-butene and allyl bromide in synthesis?

Allyl bromide (3-bromo-1-propene) has the C–Br bond directly adjacent to the double bond (allylic position), making it highly reactive toward SN2 and prone to SN1 pathways due to allylic stabilization. 4-Bromo-1-butene has one additional methylene unit separating the alkene and the bromide (homoallylic), resulting in a more selective primary alkyl bromide with reduced allylic reactivity. This extra carbon spacer alters the ring sizes accessible by cyclization and the conformational properties of products.

References

1. March, J.; Smith, M. B. March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 7th ed.; Wiley: Hoboken, NJ, 2013.
2. Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed.; Oxford University Press: Oxford, 2012.
3. Grubbs, R. H. (Ed.) Handbook of Metathesis; Wiley-VCH: Weinheim, 2003.
4. Aladdin Scientific Product Page: 4-Bromo-1-butene, SKU B106906.

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