3-Cyclopropylmethoxy-4-difluoromethoxybenzoic acid
[CAS# 162401-62-9]

Identification

• Classification: Organic raw materials >> Carboxylic compounds and derivatives
• Name: 3-Cyclopropylmethoxy-4-difluoromethoxybenzoic acid
• Molecular Formula: C₁₂H₁₂F₂O₄
• Molecular Weight: 258.22
• CAS Registry Number: 162401-62-9
• EC Number: 605-288-7
• SMILES: C1CC1COC2=C(C=CC(=C2)C(=O)O)OC(F)F

Properties

• Density: 1.4±0.1 g/cm³, Calc.^*
• Melting point: 118-120 °C (Expl.)
• Index of Refraction: 1.528, Calc.^*
• Boiling Point: 356.4±37.0 °C (760 mmHg), Calc.^*
• Flash Point: 169.4±26.5 °C, Calc.^*

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

Safety Data

• Hazard Symbols: GHS07;GHS09 Warning
• Risk Statements: H302-H315-H319-H335-H411-H413
• Safety Statements: P261-P264-P264+P265-P270-P271-P273-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P319-P321-P330-P332+P317-P337+P317-P362+P364-P391-P403+P233-P405-P501

Hazard Classification

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

Discovery and Applications

3-Cyclopropylmethoxy-4-difluoromethoxybenzoic acid is a complex organic compound featuring two distinct functional groups attached to a benzene ring: a cyclopropylmethoxy group at position 3 and a difluoromethoxy group at position 4. These unique substituents contribute to the compound’s distinctive chemical reactivity, making it a valuable building block in various fields of synthetic chemistry, including medicinal chemistry and materials science. The presence of both a strained cyclopropyl group and an electron-withdrawing difluoromethoxy group gives the molecule interesting electronic and steric properties that have been explored for potential applications in drug development and organic electronics.

The discovery of 3-cyclopropylmethoxy-4-difluoromethoxybenzoic acid is part of ongoing research into the functionalization of aromatic compounds with both electron-donating and electron-withdrawing groups. The cyclopropylmethoxy group is known for imparting steric strain to the molecule, which can influence the reactivity of the compound and make it useful in specific chemical reactions. The difluoromethoxy group, on the other hand, is an electron-withdrawing group that can stabilize certain reactive intermediates and influence the compound’s solubility and metabolic stability. These properties make 3-cyclopropylmethoxy-4-difluoromethoxybenzoic acid an attractive candidate for use in synthetic chemistry, particularly in the design of complex bioactive molecules.

In medicinal chemistry, this compound has been studied as a potential intermediate for the synthesis of novel pharmaceuticals. The cyclopropylmethoxy group introduces a unique steric effect, which can be used to control the three-dimensional structure of drug candidates, enhancing their interaction with biological targets. The difluoromethoxy group contributes to increased metabolic stability, as it can reduce the rate of degradation by enzymes. This combination of properties makes 3-cyclopropylmethoxy-4-difluoromethoxybenzoic acid a useful scaffold for the development of drugs with improved bioavailability and selectivity for specific receptors or enzymes.

The compound’s ability to influence electronic properties also makes it a valuable material in the field of organic electronics. The difluoromethoxy group, with its electron-withdrawing nature, can affect the electronic structure of organic semiconductors, potentially improving their performance in devices such as organic light-emitting diodes (OLEDs) or organic photovoltaics (OPVs). The cyclopropylmethoxy group may contribute to the rigidity of the molecule, enhancing the mechanical properties of the materials when incorporated into thin films or other electronic components. Researchers have begun exploring the potential of such compounds to improve the efficiency and stability of organic electronic devices.

Moreover, the reactivity of 3-cyclopropylmethoxy-4-difluoromethoxybenzoic acid in various chemical transformations makes it a versatile intermediate for the synthesis of other complex organic molecules. Its ability to undergo nucleophilic substitution reactions and form adducts with other electrophiles makes it useful in the creation of new materials with tailored properties. This opens up opportunities for further research and innovation in both drug discovery and materials science.

In conclusion, 3-cyclopropylmethoxy-4-difluoromethoxybenzoic acid is a promising compound with significant potential in medicinal chemistry and materials science. Its unique combination of steric and electronic effects, derived from the cyclopropylmethoxy and difluoromethoxy substituents, offers exciting possibilities for the development of novel therapeutic agents and advanced organic materials. Ongoing research continues to explore its applications, particularly in drug design and organic electronics.

References

2020. Direct Oxidation of Primary Alcohols to Carboxylic Acids. Synthesis, 52(24), 3825-3834.
DOI: 10.1055/s-0040-1706102

2015. Roflumilast. Pharmaceutical Substances.
URL: https://pharmaceutical-substances.thieme.com/ps/search-results?docUri=KD-18-0068

2013. Synthesis and structure confirmation of the impurity in crude roflumilast product. Research on Chemical Intermediates, 40(2), 665-672.
DOI: 10.1007/s11164-013-1187-z