(Bromomethyl)cyclopropane: Properties, Handling & Synthesis Guide

(Bromomethyl)cyclopropane is a versatile primary alkyl bromide building block widely employed in organic synthesis as an alkylating agent and as a precursor for cyclopropylmethyl and homoallyl transformations.

CAS Number

7051-34-5

Molecular Formula

C4H7Br

Molecular Weight

135.00 g/mol

Appearance

Colorless to pale yellow liquid

Boiling Point

~108–110 °C at 760 mmHg

Density

~1.39 g/mL at 25 °C

Reactivity Class

Primary alkyl bromide; SN2-active

Storage Condition

Cool, dry, well-ventilated area; away from light and ignition sources

Chemical Identity and Physical Properties

(Bromomethyl)cyclopropane (synonym: cyclopropylmethyl bromide; CAS 7051-34-5) has the molecular formula C₄H₇Br and a molecular weight of 135.00 g/mol. It consists of a cyclopropane ring bearing a –CH₂Br group at the exocyclic position, classifying it as a primary alkyl bromide.

The compound is a colorless to pale yellow liquid with a boiling point of approximately 108–110 °C at atmospheric pressure and a density of approximately 1.39 g/mL at 25 °C. It is sparingly soluble in water but miscible with common organic solvents including diethyl ether, tetrahydrofuran (THF), dichloromethane, and acetone.

A notable structural feature is the strained cyclopropane ring adjacent to the methylene bromide unit. Under Lewis acid or radical conditions, this strain can facilitate ring-opening reactions that generate homoallylic intermediates, distinguishing (bromomethyl)cyclopropane from simple primary alkyl bromides.

Synthetic Applications

(Bromomethyl)cyclopropane serves as a primary alkylating agent in a broad range of synthetic transformations. Its principal applications include:

• SN2 Alkylation: The primary C–Br bond undergoes efficient bimolecular nucleophilic substitution with soft nucleophiles such as thiolates, amines, malonate anions, and phenolates under mild conditions, enabling introduction of the cyclopropylmethyl group into target scaffolds.
• Grignard and Organometallic Reagent Preparation: Treatment with magnesium in anhydrous ether or THF yields cyclopropylmethylmagnesium bromide, a useful Grignard reagent for 1,2-addition reactions to aldehydes, ketones, and esters.
• Metal-Catalyzed Cross-Coupling: (Bromomethyl)cyclopropane can participate in transition-metal-catalyzed reactions (e.g., Suzuki, Negishi, Kumada-type couplings) when activated with appropriate catalysts, providing cyclopropylmethyl-substituted products.
• Ring-Opening Pathways: Under Lewis acid promotion or radical initiation, the cyclopropylcarbinyl system can undergo rapid ring opening to the homoallylic bromide (3-butenyl bromide), enabling access to homoallylic intermediates from a single reagent.
• Pharmaceutical and Agrochemical Synthesis: The cyclopropylmethyl motif is found in numerous bioactive molecules; (bromomethyl)cyclopropane provides a direct handle for introducing this pharmacophore during medicinal chemistry campaigns.

Safe Handling, Storage, and Waste Disposal

Hazard Profile: (Bromomethyl)cyclopropane is a flammable liquid and a lachrymator. It is an irritant to skin, eyes, and the respiratory tract, and the bromide may pose alkylating hazard upon prolonged exposure. Always consult the current Safety Data Sheet (SDS) before use.

Personal Protective Equipment (PPE): Use chemical-resistant gloves (nitrile or neoprene), safety goggles, and a laboratory coat. All operations should be conducted in a well-ventilated fume hood to prevent inhalation of vapors.

Storage: Store in a tightly sealed container in a cool (2–8 °C recommended for long-term stability), dry, well-ventilated area away from heat, open flames, and incompatible materials such as strong oxidizers, strong bases, and reactive metals. Protect from light to minimize decomposition.

Stability and Incompatibilities: The compound is stable under recommended storage conditions. It is incompatible with strong reducing agents, alkali metals, and strong Lewis or Brønsted acids that could promote undesired ring-opening or elimination.

Waste Disposal: Dispose of according to local, regional, and national regulations governing halogenated organic waste. Do not pour down the drain. Collect in appropriate labeled waste containers and arrange collection through a licensed hazardous-waste contractor.

Quality, Purity, and Analytical Characterization

For reliable synthetic outcomes, the purity of (bromomethyl)cyclopropane is a critical parameter. Aladdin Scientific supplies this reagent with documented purity specifications; researchers should verify the certificate of analysis (CoA) for each lot.

Recommended Analytical Methods:

• GC-FID/GC-MS: Gas chromatography is the primary technique for assessing chemical purity. The compound and common impurities (e.g., cyclopropylmethanol, homoallylic bromide) are well resolved under standard capillary column conditions.
• ¹H NMR Spectroscopy: Characteristic signals include the cyclopropane ring protons (multiplets, δ 0.2–0.6 and 0.8–1.0 ppm), the ring methine (δ ~1.0–1.2 ppm), and the –CH₂Br methylene (δ ~3.2–3.4 ppm).
• ¹³C NMR Spectroscopy: Key resonances appear for the cyclopropane carbons (δ ~4–10 ppm) and the –CH₂Br carbon (δ ~28–32 ppm).
• Refractive Index / Density: Physical constants can be compared against literature values as a quick identity check.

Impurities such as the ring-opened isomer (3-butenyl bromide) or oxidation products can affect reaction selectivity; researchers working on sensitive applications should use freshly opened material or verify purity by GC prior to use.

Reaction Protocol: SN2 Alkylation with a Malonate Nucleophile

The following general protocol illustrates the use of (bromomethyl)cyclopropane in a representative SN2 alkylation. Adapt conditions to your specific substrate.

Materials: (Bromomethyl)cyclopropane (Aladdin SKU B109676), diethyl malonate (or other active methylene compound), anhydrous potassium carbonate (K₂CO₃) or sodium hydride (NaH), anhydrous DMF or acetone, inert atmosphere (N₂ or Ar).

Procedure:

1. Under an inert atmosphere, dissolve the active methylene nucleophile (1.0 equiv) in anhydrous DMF (5–10 mL/mmol).
2. Add K₂CO₃ (1.5–2.0 equiv) or NaH (1.1–1.2 equiv, 60% dispersion in mineral oil, pre-washed). Stir at room temperature for 15–30 min to generate the anion.
3. Add (bromomethyl)cyclopropane (1.0–1.2 equiv) dropwise. The reaction is typically exothermic; maintain temperature with an ice bath if necessary.
4. Stir at room temperature to 60 °C (depending on substrate reactivity) for 2–12 h, monitoring by TLC or GC.
5. Upon completion, pour the mixture onto water and extract with ethyl acetate. Wash the organic layer with brine, dry over MgSO₄, filter, and concentrate under reduced pressure.
6. Purify by column chromatography or distillation as appropriate.

Notes: Minimize exposure to air and moisture. Excess base should be avoided with acid-sensitive substrates. Ring-opening side reactions are negligible under these mild nucleophilic conditions.

Frequently asked questions

What is the difference between (bromomethyl)cyclopropane and cyclopropyl bromide?

(Bromomethyl)cyclopropane (CAS 7051-34-5) has the bromine on an exocyclic methylene (–CH2Br) attached to the cyclopropane ring, making it a primary alkyl bromide that reacts readily via SN2. Cyclopropyl bromide (bromocyclopropane, CAS 4399-47-7) has the bromine directly on the ring carbon and behaves as a vinyl-like system with reduced SN2 reactivity due to the Walsh orbital character of cyclopropane.

Can (bromomethyl)cyclopropane undergo ring opening, and under what conditions?

Yes. The cyclopropylcarbinyl system is known to undergo very rapid ring opening to give the homoallylic (3-butenyl) cation or radical under cationic or radical conditions respectively. Lewis acids, strong Brønsted acids, or radical initiators can promote ring opening. Under standard SN2 conditions with soft nucleophiles (bases in aprotic solvents at mild temperatures), ring opening is minimal and the intact cyclopropylmethyl product predominates.

How should (bromomethyl)cyclopropane be stored to maximize shelf life?

Store the compound in a tightly sealed amber glass bottle in a cool, dry, well-ventilated area (2–8 °C is recommended for long-term storage) away from light, heat, moisture, and incompatible materials such as strong oxidizers and reactive metals. Always check the CoA for lot-specific purity before use, and verify purity by GC if the material has been stored for an extended period.

Is (bromomethyl)cyclopropane suitable for preparing Grignard reagents?

Yes. (Bromomethyl)cyclopropane reacts with magnesium turnings in anhydrous THF or diethyl ether under standard Grignard conditions to give cyclopropylmethylmagnesium bromide. Care should be taken because the resulting Grignard reagent can equilibrate with the ring-opened homoallylmagnesium bromide at elevated temperatures; reactions should ideally be run at low to ambient temperature to maintain cyclopropylmethyl selectivity.

What are typical signs that (bromomethyl)cyclopropane has degraded?

Degradation is typically indicated by a color change from colorless or pale yellow to amber or brown, formation of a precipitate (inorganic bromide salts from hydrolysis), or a significant drop in GC purity. A strong acidic odor or the presence of HBr may also suggest hydrolytic decomposition. Any lot showing these signs should be discarded and not used in sensitive reactions.

References

1. March, J. Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 4th ed.; Wiley-Interscience: New York, 1992.
2. Carey, F. A.; Sundberg, R. J. Advanced Organic Chemistry, Part A: Structure and Mechanisms, 5th ed.; Springer: New York, 2007.
3. Nonhebel, D. C.; Walton, J. C. Free-Radical Chemistry; Cambridge University Press: Cambridge, 1974. (Cyclopropylcarbinyl ring opening kinetics discussed.)
4. Aladdin Scientific. Certificate of Analysis, (Bromomethyl)cyclopropane, SKU B109676. [Lot-specific; consult current CoA at www.aladdin-e.com]

Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.