4-Difluoromethoxy-3-hydroxybenzaldehyde
[CAS# 151103-08-1]

Identification

• Classification: Chemical reagent >> Organic reagent >> Aromatic aldehyde (containing acetal, hemiacetal)
• Name: 4-Difluoromethoxy-3-hydroxybenzaldehyde
• Synonyms: 3-Hydroxy-4-diflouromethylbenzaldehyde
• Molecular Formula: C₈H₆F₂O₃
• Molecular Weight: 188.13
• CAS Registry Number: 151103-08-1
• EC Number: 687-745-0
• SMILES: C1=CC(=C(C=C1C=O)O)OC(F)F

Properties

• Density: 1.4±0.1 g/cm³, Calc.^*
• Melting point: 85-90 °C (Expl.)
• Index of Refraction: 1.533, Calc.^*
• Boiling Point: 280.6±35.0 °C (760 mmHg), Calc.^*
• Flash Point: 123.5±25.9 °C, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07;GHS09 Warning
• Risk Statements: H302-H315-H319-H335-H411
• Safety Statements: P261-P264-P270-P271-P273-P280-P301+P312-P302+P352-P304+P340-P305+P351+P338-P312-P330-P332+P313-P337+P313-P362-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Eye irritation	Eye Irrit.	2	H319
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335
Acute toxicity	Acute Tox.	4	H302
Chronic hazardous to the aquatic environment	Aquatic Chronic	2	H411
Chronic hazardous to the aquatic environment	Aquatic Chronic	4	H413
Eye irritation	Eye Irrit.	2A	H319

Discovery and Applications

4-Difluoromethoxy-3-hydroxybenzaldehyde is a chemical compound that belongs to the class of substituted benzaldehydes. It features a hydroxyl group at position 3 and a difluoromethoxy group at position 4 on the benzene ring. This specific substitution pattern introduces unique chemical properties, such as enhanced electron-donating effects from the hydroxyl group and electron-withdrawing effects from the difluoromethoxy group. These structural characteristics give the compound potential applications in various areas of organic chemistry, pharmaceuticals, and material science.

The discovery of 4-difluoromethoxy-3-hydroxybenzaldehyde is part of ongoing research into the development of new aromatic aldehyde derivatives with functional groups that can influence reactivity, solubility, and biological activity. Benzaldehydes are known for their versatility in synthetic chemistry, and modifications to their substituent groups can lead to significant changes in their reactivity. The introduction of difluoromethoxy and hydroxy groups onto the aromatic ring makes 4-difluoromethoxy-3-hydroxybenzaldehyde an interesting compound for further study and application.

One of the key areas of application for 4-difluoromethoxy-3-hydroxybenzaldehyde is in medicinal chemistry. The aldehyde functional group is a common feature in bioactive molecules, and the compound’s unique substituent pattern has drawn attention for its potential as a precursor in the synthesis of biologically active compounds. The difluoromethoxy group is known to impart increased metabolic stability, while the hydroxy group can provide hydrogen bonding interactions with biological targets. These properties make 4-difluoromethoxy-3-hydroxybenzaldehyde a valuable intermediate in the development of new drug candidates, especially in the search for molecules with enhanced efficacy and selective biological activity.

In addition to its medicinal applications, this compound has potential uses in material science, particularly in the development of organic semiconductors and light-emitting materials. The difluoromethoxy and hydroxy groups can influence the electronic properties of the aromatic ring, making the compound suitable for incorporation into materials for optoelectronic devices. Organic semiconductors, which are used in applications such as organic light-emitting diodes (OLEDs) and organic photovoltaic cells (OPVs), can benefit from the unique properties of substituted benzaldehydes like 4-difluoromethoxy-3-hydroxybenzaldehyde. Its electron-withdrawing and donating groups allow for fine-tuning of the electronic structure, which can improve charge transport and light emission characteristics.

4-Difluoromethoxy-3-hydroxybenzaldehyde also finds utility in the synthesis of other organic compounds. Its reactivity as an aldehyde makes it a useful starting material for various condensation reactions, such as those leading to the formation of imines or other heterocyclic structures. By modifying the aldehyde group or incorporating it into larger molecular frameworks, researchers can create a wide range of compounds with diverse applications, from fine chemicals to functional materials.

In summary, 4-difluoromethoxy-3-hydroxybenzaldehyde is a versatile compound with a broad range of potential applications. Its unique substituent pattern, consisting of a difluoromethoxy and hydroxy group, confers interesting chemical properties that make it valuable in fields such as medicinal chemistry, material science, and synthetic chemistry. Its use as an intermediate in drug development, organic electronics, and the synthesis of new chemical compounds highlights its importance in modern chemical research and industry.

References

2013. Synthesis and structure confirmation of the impurity in crude roflumilast product. Research on Chemical Intermediates, 39(8), 3783-3792.
DOI: 10.1007/s11164-013-1187-z

2012. Isolation, synthesis and structure confirmation of the impurity in crude roflumilast product. Research on Chemical Intermediates, 39(3), 1085-1095.
DOI: 10.1007/s11164-012-0823-3

2012. A convenient method for the synthesis of roflumilast. Research on Chemical Intermediates, 39(3), 1067-1076.
DOI: 10.1007/s11164-012-0742-3