4-[(4-Chlorobenzyl)oxy]-3-methoxybenzenecarbaldehyde: Lab Handling Guide

4-[(4-Chlorobenzyl)oxy]-3-methoxybenzenecarbaldehyde is a synthetic aromatic aldehyde building block featuring a vanillin-derived scaffold with a 4-chlorobenzyl ether at the para-oxygen, widely employed as an intermediate in medicinal chemistry and fine-chemical synthesis.

IUPAC Name

4-[(4-Chlorobenzyl)oxy]-3-methoxybenzaldehyde

CAS Number

To be confirmed — see SDS (SY-250424)

Molecular Formula

C₁₅H₁₃ClO₃

Molecular Weight

276.72 g/mol

Functional Groups

Aldehyde, aryl ether, methoxy

Appearance

Typically a white to off-white crystalline solid (verify with CoA)

Storage Condition

Store at room temperature in a cool, dry place away from light and moisture

Aladdin SKU

C1369288

Chemical Identity and Structure

4-[(4-Chlorobenzyl)oxy]-3-methoxybenzenecarbaldehyde (SKU C1369288) is a substituted benzaldehyde derived from the vanillin scaffold. The compound retains the characteristic 3-methoxy group of vanillin but replaces the free 4-hydroxyl with a 4-chlorobenzyl ether linkage, yielding a molecular formula of C₁₅H₁₃ClO₃ and a molecular weight of approximately 276.72 g/mol.

The molecule contains three reactive or functionally significant motifs: (1) an aldehyde group at the 1-position of the ring, amenable to nucleophilic addition, condensation, and oxidation reactions; (2) a methoxy substituent at the 3-position; and (3) a 4-chlorobenzyl ether at the 4-position, which introduces a halogenated aryl handle suitable for further cross-coupling or nucleophilic substitution chemistry. This combination makes the compound a versatile intermediate in multi-step organic synthesis.

Note: Verify CAS number, exact melting point, and purity specification against the current Certificate of Analysis (CoA) and Safety Data Sheet (SDS reference SY-250424) supplied with each lot.

Handling, Safety, and Storage

Personal Protective Equipment (PPE): When handling 4-[(4-Chlorobenzyl)oxy]-3-methoxybenzenecarbaldehyde, wear appropriate laboratory PPE including nitrile gloves, a laboratory coat, and safety goggles. Work in a well-ventilated area or under a fume hood, particularly when weighing or dissolving the compound, to minimise inhalation of dust or vapour.

Storage: Store the compound at room temperature in a tightly sealed container in a cool, dry location away from direct light, heat sources, and moisture. Keep away from strong oxidisers and reducing agents. Ensure the container is clearly labelled and segregated from incompatible materials in accordance with your institution's chemical storage policy.

Waste Disposal: Dispose of waste material in accordance with local environmental regulations and your institutional chemical waste management procedures. Do not dispose of down the drain. Consult the SDS (reference SY-250424) for specific hazard classifications and first-aid measures before use.

Review flag: Specific GHS hazard categories, H-statements, and P-statements must be confirmed from the current SDS (SY-250424) — do not rely solely on this guideline for safety decisions.

Solubility and Solution Preparation

As a lipophilic aromatic aldehyde, 4-[(4-Chlorobenzyl)oxy]-3-methoxybenzenecarbaldehyde is expected to show good solubility in common polar aprotic solvents such as dimethyl sulfoxide (DMSO), dimethylformamide (DMF), and dichloromethane (DCM), as well as in ethyl acetate and tetrahydrofuran (THF). Solubility in water is anticipated to be low due to the hydrophobic 4-chlorobenzyl ether moiety.

Recommended preparation protocol:

1. Accurately weigh the required mass using a calibrated analytical balance in a fume hood.
2. Transfer to an appropriate glass vial and add a minimal volume of DMSO or DCM to dissolve fully with gentle mixing or brief sonication.
3. If aqueous buffers are required (e.g., for biological assays), prepare a concentrated stock in DMSO (typically ≤10 mM) and dilute into aqueous buffer to keep the final DMSO concentration ≤1% v/v to avoid solvent artefacts.
4. Filter through a 0.22 µm PTFE syringe filter if particulate-free solutions are required.
5. Store prepared solutions under inert atmosphere (nitrogen or argon) at −20 °C and protect from light to minimise aldehyde oxidation.

Review flag: Exact solubility values (mg/mL) in specific solvents have not been confirmed from the source material; experimental determination is recommended.

Applications in Organic Synthesis and Research

4-[(4-Chlorobenzyl)oxy]-3-methoxybenzenecarbaldehyde serves as a multifunctional building block in synthetic organic chemistry. Its principal applications include:

• Schiff base and imine formation: The reactive aldehyde condenses readily with primary amines to form imines (Schiff bases), which are common precursors to pharmacologically active compounds, ligands, and dyes.
• Knoevenagel and aldol condensations: The activated benzaldehyde undergoes Knoevenagel condensation with active methylene compounds (e.g., malononitrile, Meldrum's acid) to yield α,β-unsaturated products with potential biological activity.
• Reductive amination: In the presence of a reducing agent (e.g., NaBH₃CN, NaBH(OAc)₃), the aldehyde can be used in reductive amination to install a homoveratrylamine-type fragment onto nitrogen-containing scaffolds.
• Cross-coupling and further functionalisation: The aromatic chloride on the benzyl ether moiety provides an additional handle for palladium-catalysed cross-coupling reactions (e.g., Suzuki, Buchwald–Hartwig), enabling rapid diversification of the molecular scaffold.
• Medicinal chemistry intermediates: Vanillin-derived aldehydes bearing aryloxy substituents are reported in the literature as precursors to compounds with antimicrobial, anticancer, and enzyme-inhibitory properties.

Review flag: Specific biological activity or reported IC₅₀ values for this exact compound are not confirmed in the source material; literature references should be sought and cited independently.

Quality, Purity, and Analytical Verification

Aladdin Scientific supplies 4-[(4-Chlorobenzyl)oxy]-3-methoxybenzenecarbaldehyde (C1369288) as a research-grade reagent. Each lot is accompanied by a Certificate of Analysis (CoA) that specifies purity, appearance, and relevant physicochemical data determined by the manufacturer.

Recommended verification techniques:

• TLC/HPLC: Thin-layer chromatography or reverse-phase HPLC provides a rapid assessment of compound purity. An appropriate HPLC method would use a C18 column with an acetonitrile–water gradient and UV detection at 254 nm or 280 nm, given the aromatic chromophore.
• ¹H NMR: Proton NMR in CDCl₃ or DMSO-d₆ should confirm the aldehyde proton (δ ~9.8–10.0 ppm, singlet), ArH protons, OCH₂ benzylic protons (~5.1–5.2 ppm, singlet), and OCH₃ (~3.9 ppm, singlet). Integration ratios must match the expected structure.
• IR spectroscopy: A strong C=O stretch near 1680–1700 cm⁻¹ is characteristic of an aromatic aldehyde. The C–O–C ether stretches near 1250 and 1050 cm⁻¹ should also be present.
• Mass spectrometry: ESI-MS or APCI-MS should show [M+H]⁺ at m/z 277.1 (for ³⁵Cl isotope) with a characteristic M+2 chlorine isotope pattern.

Review flag: Specific purity specification (e.g., ≥97%, ≥98%) and exact NMR chemical shifts must be confirmed from the CoA (SDS reference SY-250424). The MS values stated here are calculated from molecular formula and are consistent with C₁₅H₁₃ClO₃; verify experimentally.

Frequently asked questions

What solvents are recommended for dissolving 4-[(4-Chlorobenzyl)oxy]-3-methoxybenzenecarbaldehyde?

DMSO, DMF, DCM, ethyl acetate, and THF are recommended as primary solvents. Water solubility is expected to be low due to the hydrophobic chlorobenzyl ether group. For biological assays requiring aqueous media, prepare a concentrated DMSO stock and dilute to keep final DMSO ≤1% v/v.

How should I store 4-[(4-Chlorobenzyl)oxy]-3-methoxybenzenecarbaldehyde to maintain stability?

Store the neat compound at room temperature in a tightly sealed container in a cool, dry, dark location away from oxidisers. Solutions should be stored at −20 °C under an inert atmosphere (N₂ or Ar) and protected from light to prevent aldehyde oxidation to the corresponding carboxylic acid.

What analytical methods can confirm the identity and purity of this compound?

Identity can be confirmed by ¹H NMR (aldehyde singlet at ~9.8–10.0 ppm; benzylic OCH₂ singlet at ~5.1–5.2 ppm), IR (C=O stretch ~1680–1700 cm⁻¹), and ESI-MS ([M+H]⁺ at m/z 277.1 with chlorine isotope pattern). Purity is best assessed by reverse-phase HPLC with UV detection at 254 nm. Always cross-reference with the CoA supplied with each lot.

Can 4-[(4-Chlorobenzyl)oxy]-3-methoxybenzenecarbaldehyde be used in cross-coupling reactions?

Yes. The 4-chloro substituent on the benzyl ether provides a handle for palladium-catalysed cross-coupling reactions such as Suzuki–Miyaura and Buchwald–Hartwig couplings, enabling further diversification of the molecular scaffold. Optimisation of palladium catalyst, ligand, base, and solvent is recommended for best yields.

Where can I find the Safety Data Sheet (SDS) for this product?

The Safety Data Sheet for 4-[(4-Chlorobenzyl)oxy]-3-methoxybenzenecarbaldehyde (SDS reference SY-250424) is available from Aladdin Scientific. Contact our customer service team or visit the product page for SKU C1369288 on the Aladdin Scientific website to download the current SDS before handling the material.

References

1. Aladdin Scientific. Product Information and Safety Data Sheet: 4-[(4-Chlorobenzyl)oxy]-3-methoxybenzenecarbaldehyde, SKU C1369288, SDS Reference SY-250424. Aladdin Scientific Corp.
2. March, J. Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 4th ed. Wiley-Interscience, 1992. (General reference for aldehyde reactivity, Knoevenagel condensation, reductive amination, and imine formation.)
3. Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed. Oxford University Press, 2012. (Textbook-level reference for aromatic aldehyde chemistry and cross-coupling reactions.)

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