1-(4-Chlorophenyl)-1-cyclopropanemethanol: Properties & Uses

1-(4-Chlorophenyl)-1-cyclopropanemethanol is a structurally distinctive secondary alcohol featuring a cyclopropane ring and a para-chlorophenyl substituent, making it a valuable building block in pharmaceutical and fine-chemical synthesis.

Chemical Name

1-(4-Chlorophenyl)-1-cyclopropanemethanol

SKU / Catalog Number

C771038

Molecular Formula

C₁₀H₁₁ClO

Compound Class

Aryl cyclopropane secondary alcohol

Key Functional Groups

Secondary hydroxyl (–OH), cyclopropane ring, para-chlorophenyl group

Primary Application

Pharmaceutical intermediate and synthetic building block

Chemical Structure and Physicochemical Properties

1-(4-Chlorophenyl)-1-cyclopropanemethanol (molecular formula C₁₀H₁₁ClO) belongs to the class of aryl cyclopropane secondary alcohols. Its structure consists of a cyclopropane ring bearing both a hydroxymethyl group and a para-chlorophenyl substituent at the same carbon, creating a sterically constrained chiral center.

The cyclopropane ring imparts unique electronic and conformational properties compared with simple aliphatic systems: the ring bonds exhibit partial π-character through Walsh orbital interactions, which can influence reactivity at adjacent positions. The para-chloro substituent on the phenyl ring is mildly electron-withdrawing, affecting the acidity of the hydroxyl group and the electrophilicity of the benzylic carbon.

Key physicochemical characteristics expected for this class of compound include moderate lipophilicity (log P estimated in the range of 2–3, pending experimental confirmation), limited water solubility, and stability under standard laboratory storage conditions when kept away from strong oxidants and bases. The secondary alcohol group is amenable to a range of transformations including oxidation, esterification, and halogenation.

Synthesis and Role as a Building Block

Aryl cyclopropane methanols such as 1-(4-Chlorophenyl)-1-cyclopropanemethanol are typically accessed via nucleophilic addition of cyclopropyllithium or a cyclopropyl Grignard reagent (e.g., cyclopropylmagnesium bromide) to a para-chlorobenzaldehyde, followed by aqueous workup. This retrosynthetic disconnection is straightforward and scalable, making the compound readily available for multi-gram preparative purposes.

Alternatively, reduction of the corresponding ketone — 1-(4-chlorophenyl)-1-cyclopropan-1-yl methanone (or cyclopropyl 4-chlorophenyl ketone) — using sodium borohydride or lithium aluminum hydride furnishes the racemic alcohol. Asymmetric reduction using chiral CBS catalysts or biocatalytic ketoreductases can provide enantioenriched material where stereochemistry is relevant to downstream applications.

As a building block, the compound offers several synthetic handles: (1) the hydroxyl can be activated as a mesylate or tosylate for SN2 displacement; (2) oxidation yields the ketone precursor; (3) acid-catalyzed ring-opening of the strained cyclopropane can provide homoallylic or ring-opened intermediates. These versatile transformations make it attractive for library synthesis and lead optimization campaigns in drug discovery.

Research and Pharmaceutical Applications

1-(4-Chlorophenyl)-1-cyclopropanemethanol and its structural analogs occupy an important niche in medicinal chemistry. The combination of a strained cyclopropane ring with an aryl group and a hydrogen-bond-donating hydroxyl provides a three-dimensional scaffold with favorable drug-like properties, including conformational rigidity that can improve selectivity when binding to biological targets.

Compounds bearing the 4-chlorophenyl motif are well-represented in bioactive molecules targeting receptors and enzymes across CNS, antifungal, and agrochemical fields. The cyclopropane ring itself is a well-documented bioisostere for double bonds and carbonyl groups, and its inclusion often modulates metabolic stability by resisting cytochrome P450-mediated oxidation.

In a research context, this compound may serve as: (a) an intermediate in the preparation of cyclopropane-containing drug candidates; (b) a reference standard for analytical method development; (c) a probe molecule in structure-activity relationship (SAR) studies exploring the effect of ring strain and halogen substitution on biological activity. Researchers in synthetic chemistry, medicinal chemistry, and chemical biology will find it a versatile reagent.

Handling, Storage, and Safety Considerations

As with most aryl chloride-containing organic compounds, 1-(4-Chlorophenyl)-1-cyclopropanemethanol should be handled following standard laboratory safety practices. Personnel should wear appropriate personal protective equipment (PPE) including chemical-resistant gloves, safety goggles, and a lab coat. Operations generating dust or aerosols should be conducted in a fume hood.

The compound should be stored in a tightly sealed container in a cool, dry, well-ventilated area, away from incompatible materials such as strong oxidizing agents, strong bases, and reactive metals. Typical recommended storage temperatures for such solid or low-melting organic reagents are 2–8 °C or room temperature under inert atmosphere, depending on the specific physical form supplied.

Disposal must comply with local, regional, and national regulations governing organic chemical waste. Users should consult the Safety Data Sheet (SDS) provided by Aladdin Scientific for complete hazard classifications, first-aid measures, and disposal guidance specific to this product before use.

Frequently asked questions

What is 1-(4-Chlorophenyl)-1-cyclopropanemethanol used for in research?

It is primarily used as a pharmaceutical intermediate and synthetic building block in medicinal chemistry. Its cyclopropane ring and para-chlorophenyl group make it useful for constructing drug-like scaffolds, conducting SAR studies, and serving as a reference standard in analytical chemistry workflows.

How should 1-(4-Chlorophenyl)-1-cyclopropanemethanol be stored to maintain stability?

The compound should be stored in a tightly sealed container in a cool, dry, and well-ventilated location, away from strong oxidants and bases. Depending on the supplied form, storage at 2–8 °C under an inert atmosphere is recommended. Always refer to the product SDS for specific storage conditions.

What synthetic routes are available to prepare 1-(4-Chlorophenyl)-1-cyclopropanemethanol?

The compound can be prepared by nucleophilic addition of a cyclopropyl Grignard reagent or cyclopropyllithium to 4-chlorobenzaldehyde, or by reduction of the corresponding cyclopropyl 4-chlorophenyl ketone using NaBH₄ or LiAlH₄. Asymmetric reduction with chiral catalysts or ketoreductases can yield enantioenriched product when stereochemical purity is required.

Is 1-(4-Chlorophenyl)-1-cyclopropanemethanol available as a single enantiomer?

Aladdin Scientific lists the racemic form under SKU C771038. For enantiomerically enriched material, asymmetric synthetic routes or chiral resolution would need to be employed. Please contact Aladdin Scientific technical support for availability of specific stereoisomers.

What are the key chemical reactions that 1-(4-Chlorophenyl)-1-cyclopropanemethanol can undergo?

The secondary hydroxyl group can be oxidized to the ketone, esterified, or converted to a leaving group (mesylate/tosylate) for substitution reactions. The strained cyclopropane ring can undergo acid-catalyzed ring-opening to provide ring-expanded or homoallylic intermediates, and the aryl chloride can participate in transition-metal-catalyzed cross-coupling reactions.

References

1. March, J.; Smith, M. B. March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 7th ed.; Wiley: Hoboken, NJ, 2013.
2. Wessjohann, L. A.; Brandt, W.; Thiemann, T. Biosynthesis and Metabolism of Cyclopropane Rings in Natural Compounds. Chem. Rev. 2003, 103, 1625–1647. doi:10.1021/cr010299n
3. Faust, R. Fascinating Natural and Artificial Cyclopropane Architectures. Angew. Chem. Int. Ed. 2001, 40, 2251–2253.
4. Corey, E. J.; Helal, C. J. Reduction of Carbonyl Compounds with Chiral Oxazaborolidine Catalysts: A New Paradigm for Enantioselective Catalysis and a Powerful New Synthetic Method. Angew. Chem. Int. Ed. 1998, 37, 1986–2012.

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