4-Hydroxyisophthalaldehyde: Handling & Application Protocol

4-Hydroxyisophthalaldehyde is a bifunctional aromatic building block bearing both a phenolic hydroxyl group and two aldehyde moieties, making it a versatile reagent for constructing Schiff bases, covalent organic frameworks, and luminescent sensor scaffolds.

Chemical Name

4-Hydroxyisophthalaldehyde

SKU

H157418

Molecular Formula

C8H6O3

Molecular Weight

150.13 g/mol

Key Functional Groups

Two aldehyde groups (–CHO) and one phenolic hydroxyl group (–OH) on an isophthalic scaffold

Recommended Storage

Cool, dry place away from light; seal tightly under inert atmosphere after opening

Primary Applications

Schiff base formation, MOF/COF construction, fluorescent probes, macrocycle synthesis

Compound Overview and Properties

4-Hydroxyisophthalaldehyde (CAS not confirmed in source material; flag for review) is an aromatic dialdehyde derived from the isophthalic acid skeleton, with a hydroxyl substituent at the 4-position of the benzene ring. Its molecular formula is C₈H₆O₃ and molecular weight is approximately 150.13 g/mol.

The compound possesses three reactive sites: two electrophilic aldehyde carbons capable of condensation with amines, hydrazines, or hydroxamic acids, and one nucleophilic phenolic –OH group available for O-alkylation, O-acylation, or coordination with metal centres. This trifunctionality underpins its broad utility as a molecular building block.

Physically, 4-Hydroxyisophthalaldehyde is typically a pale-yellow to white crystalline solid at room temperature. It exhibits moderate solubility in polar aprotic solvents such as DMSO and DMF, limited solubility in ethanol and acetone, and low solubility in water and non-polar solvents. Exact melting point and spectroscopic data should be confirmed against the certificate of analysis supplied with SKU H157418.

Safe Handling and Storage

Personal Protective Equipment (PPE): Always wear nitrile gloves, safety goggles, and a laboratory coat when handling 4-Hydroxyisophthalaldehyde. Work in a well-ventilated fume hood, particularly during weighing operations, to avoid inhalation of dust or vapours.

Storage conditions: Store the compound in a tightly sealed container in a cool (15–25 °C), dry location protected from light. After opening, purge the headspace with dry nitrogen or argon before resealing to minimise moisture ingress and oxidative degradation of the aldehyde groups.

Stability notes: Aldehydes can be susceptible to aerial oxidation to the corresponding carboxylic acids over time. Inspect the material visually and by TLC or NMR before use in sensitive applications if the container has been opened previously.

Waste disposal: Dispose of residues according to local regulations for aromatic organic compounds. Do not pour into drains. Consult the Safety Data Sheet (SDS) for SKU H157418 for full hazard classification and first-aid measures.

Solution Preparation Protocol

Recommended solvents: DMSO and DMF are the preferred solvents for stock solution preparation due to the compound's good solubility in these media. Ethanol may be used for applications requiring protic media, though heating to ~50 °C may aid dissolution.

Step-by-step procedure:

1. Allow the sealed container to equilibrate to room temperature before opening to prevent condensation on the solid.
2. Tare a clean, dry glass vial on an analytical balance.
3. Transfer the required mass of 4-Hydroxyisophthalaldehyde (H157418) using a dry spatula. Avoid prolonged exposure to ambient air.
4. Add the appropriate volume of dry, anhydrous solvent (e.g., anhydrous DMSO) to achieve the desired concentration. For a 100 mM stock solution: dissolve 15.0 mg in approximately 1.0 mL DMSO.
5. Cap the vial and vortex or stir gently at room temperature until fully dissolved. Sonication may assist dissolution.
6. Filter through a 0.22 µm PTFE syringe filter if particulate-free solutions are required.
7. Store stock solutions at –20 °C under inert atmosphere and protect from light. Verify stability by checking for precipitation or colour change before use.

Note: Concentration values are illustrative; confirm solubility limits experimentally for your specific application and solvent system.

Key Synthetic Applications

4-Hydroxyisophthalaldehyde's unique combination of functional groups enables its use across several advanced research domains:

1. Schiff Base and Imine Formation: The two aldehyde groups react readily with primary amines under mild conditions (room temperature to 60 °C, often without catalyst) to yield bis-imine (Schiff base) products. These intermediates are widely used as ligands for transition metal complexes and as precursors to macrocyclic or polymeric architectures. The phenolic –OH further enriches the coordination sphere.

2. Covalent Organic Frameworks (COFs) and Metal-Organic Frameworks (MOFs): As a bifunctional aldehyde linker with an additional –OH anchor, 4-Hydroxyisophthalaldehyde is suitable for constructing two-dimensional or three-dimensional porous frameworks. The phenol oxygen can participate in hydrogen bonding or post-synthetic metalation, tuning pore environment and functionality.

3. Fluorescent Probes and Chemosensors: The electron-deficient aromatic aldehyde system, conjugated with the phenolic donor, creates a push-pull electronic structure amenable to fluorescence-based detection. Derivatives synthesised from this compound have been explored for sensing metal ions and reactive species.

4. Macrocycle and Cage Synthesis: In combination with diamines or polyamines, the dialdehyde unit directs the formation of [2+3] or [4+6] condensation products (macrocycles, cages), which are of interest in supramolecular chemistry, host-guest chemistry, and molecular recognition.

Troubleshooting and Quality Control

Poor solubility: If the compound fails to dissolve completely, warm the solvent gently (40–50 °C) and sonicate. Avoid temperatures above 80 °C to prevent decomposition. Switch to DMSO if using a less polar solvent.

Unexpected colour change: A deepening yellow or brown colour in the solid or solution may indicate oxidation of aldehyde groups to carboxylic acids or formation of aldol condensation by-products. Re-characterise by ¹H NMR (aldehyde protons typically appear at δ 9.8–10.3 ppm) and IR (carbonyl stretches ~1680–1700 cm^-1 for aromatic aldehydes).

Low imine yield in Schiff base synthesis: Ensure the amine substrate is anhydrous. Use molecular sieves (3 Å or 4 Å) to sequester water generated during condensation. Dean-Stark azeotropic removal of water is also effective in toluene or xylene systems.

Quality control checks: Confirm identity and purity of H157418 by TLC (suitable eluent: ethyl acetate/hexane mixtures), ¹H/¹³C NMR, and HPLC before use in critical experiments. Refer to the certificate of analysis for lot-specific purity data.

Frequently asked questions

What solvents are best for dissolving 4-Hydroxyisophthalaldehyde?

DMSO and DMF provide the best solubility for 4-Hydroxyisophthalaldehyde. Ethanol can also be used with gentle warming (~50 °C). Water and non-polar solvents such as hexane are not recommended due to poor solubility.

How should 4-Hydroxyisophthalaldehyde be stored to maintain stability?

Store the compound in a tightly sealed container at 15–25 °C, away from light and moisture. After opening, purge with dry nitrogen or argon before resealing. Stock solutions in DMSO should be kept at –20 °C under inert atmosphere.

Can 4-Hydroxyisophthalaldehyde be used directly to build metal-organic frameworks?

Yes. The compound's dual aldehyde groups can condense with amine linkers to form imine-linked COFs, while the phenolic –OH group can coordinate to metal nodes or participate in hydrogen-bonding networks, making it a versatile linker for MOF and COF construction. Specific solvothermal conditions depend on the target framework and should be optimised experimentally.

How can I confirm the purity of H157418 before use?

Check the lot-specific certificate of analysis provided with the product. For additional in-house verification, perform TLC using ethyl acetate/hexane as eluent, and confirm aldehyde proton signals by 1H NMR (δ ~9.8–10.3 ppm). HPLC can also be used for quantitative purity assessment.

Is 4-Hydroxyisophthalaldehyde suitable for fluorescent probe synthesis?

Yes. The conjugated push-pull electronic system created by the electron-withdrawing aldehyde groups and the electron-donating phenol on the aromatic ring makes derivatives of this compound promising fluorophore precursors. It has been explored in the synthesis of chemosensors for metal ions and reactive oxygen species, though specific performance data depend on the final probe structure.

References

1. Aladdin Scientific product page and certificate of analysis for 4-Hydroxyisophthalaldehyde, SKU H157418.
2. Textbook reference: March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure. Smith, M. B. Wiley, 8th ed. (general Schiff base condensation chemistry).
3. General reference on COF synthesis using aromatic dialdehydes and amines: Diercks, C. S.; Yaghi, O. M. Science 2017, 355, eaal1585. (COF chemistry background; specific applicability to this compound needs verification.) doi:10.1126/science.aal1585

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