Among partially fluorinated aromatic acids, 2,3,5,6-tetrafluoro-4-methoxybenzoic acid (CAS 3153-01-3) is notable for a substitution pattern that leaves the ring with only one strongly electron-donating substituent. Four ring fluorines withdraw electron density and occupy the positions that would otherwise be open to oxidation, while the para-methoxy group supplies the only significant electron-donating effect in the molecule. For process and discovery chemists, that combination is usually the reason this scaffold is selected at all: it delivers a benzoic acid that is simultaneously more electron-poor and more resistant to ring oxidation than the parent compound.
KEY IDENTITY DATA
CAS number: 3153-01-3
IUPAC name: 2,3,5,6-tetrafluoro-4-methoxybenzoic acid
Molecular formula: C8H4F4O3
Molecular weight: 224.11 g/mol
Appearance: white crystalline solid
Melting point: 122-124 degrees C
MDL number: MFCD00129961
PubChem CID: 952397
WHY THE SUBSTITUTION PATTERN MATTERS
The 2,3,5,6-tetrafluoro pattern places a fluorine at every ring position not occupied by the carboxylic acid and the methoxy group. Fluorine is small enough to substitute for hydrogen without major steric change, but its electronegativity lowers the energy of the aromatic system and deactivates the ring toward electrophilic attack. In practice, this shifts the chemistry away from ring functionalization and toward the two handles the molecule does offer: the carboxylic acid and the methoxy ether.
The methoxy group is the exception to that electron-poor picture. It is a weak director that reinforces the para relationship with the acid, and it can be converted to the corresponding phenol by demethylation when a 4-hydroxy-2,3,5,6-tetrafluorobenzoic acid derivative is wanted instead. Because the four ring fluorines remain in place throughout, the tetrafluoro substitution pattern survives transformations that would otherwise alter the ring.
THE CARBOXYLIC ACID AS THE MAIN DERIVATIZATION POINT
Most downstream work on this building block starts at the acid. Standard transformations include:
- Esterification to methyl, ethyl or higher alkyl 2,3,5,6-tetrafluoro-4-methoxybenzoates, which are useful where a more lipophilic or volatile derivative is needed.
- Amide coupling with aliphatic or aromatic amines, giving fluorinated benzamides for screening libraries and process intermediates.
- Conversion to the corresponding benzoyl chloride, which is the more reactive acylating form when the acid itself reacts too slowly. The acid chloride analogue, 2,3,5,6-tetrafluoro-4-methoxybenzoyl chloride (CAS 107535-74-0), is stocked separately and is often the preferred starting point for large-scale acylation.
TYPICAL DOWNSTREAM USE
The compound is supplied as a research and industrial building block rather than as an active substance. Typical work includes:
- Preparation of fluorinated benzoate esters and amides for pharmaceutical and agrochemical discovery, where ring fluorination is used to slow oxidative metabolism and to tune lipophilicity.
- Synthesis of tetrafluorinated phenol derivatives through demethylation, giving intermediates that are difficult to access by direct ring fluorination.
- Ligand and scaffold work in materials and specialty chemical research, where a rigid, electron-poor aromatic core is wanted.
HANDLING AND STORAGE
The material is a carboxylic acid and should be handled as an irritant, with gloves, eye protection and local exhaust ventilation. It is stable at room temperature when kept dry. Store in a tightly closed container, protected from moisture and direct light, and segregate from strong bases and oxidizing agents. Bulk quantities should be kept in a cool, dry store away from sources of ignition.
QUALITY DOCUMENTATION AND SUPPLY
H2-CHEM supplies CAS 3153-01-3 as a catalog item at 97% purity, with a lot-based Certificate of Analysis issued for each batch. Because the acid is hygroscopic in humid conditions and the melting point range is a useful identity check, both assay and melting point data are reported per lot. Packaging is available in laboratory and pilot-scale quantities, and export documentation can be prepared for the destination country on request.
For current stock, packaging options and pricing, see the product page at www.h2-chem.cn/product.php?id=2530 or send your specification and required quantity to sales@h2-chem.cn. Related fluorinated aromatic acids and acid chlorides, including CAS 107535-74-0, are listed in the fluorinated compounds catalog.
NOTE: This product is intended for research, development and industrial manufacturing use. It is not for diagnostic, therapeutic or veterinary use.
