2-Nitro-4-((trifluoromethyl)thio)phenol: Properties & Applications
2-Nitro-4-((trifluoromethyl)thio)phenol: Properties & Applications
2-Nitro-4-((trifluoromethyl)thio)phenol is a fluorinated aromatic building block bearing both a nitro group and a trifluoromethylthio (SCF3) substituent on a phenolic scaffold, making it a versatile intermediate for medicinal chemistry and agrochemical synthesis.
- Product Name
- 2-Nitro-4-((trifluoromethyl)thio)phenol
- SKU
- N731573
- Key Functional Groups
- Phenol (–OH), Nitro (–NO₂), Trifluoromethylthio (–SCF₃)
- Primary Application Area
- Pharmaceutical and agrochemical intermediate synthesis
- Molecular Framework
- Ortho-nitro, para-SCF₃ substituted phenol
- Significance of SCF₃ Group
- Enhances lipophilicity and metabolic stability in drug candidates
Chemical Identity and Structure
2-Nitro-4-((trifluoromethyl)thio)phenol (SKU N731573) is an aromatic compound featuring a phenolic hydroxyl group, a nitro substituent at the 2-position (ortho), and a trifluoromethylthio (–SCF₃) group at the 4-position (para). This combination of electron-withdrawing groups on the aromatic ring results in a highly activated scaffold with distinctive electronic properties.
The –SCF₃ moiety is recognized as one of the most lipophilicity-enhancing groups available in medicinal chemistry, with a Hansch π value significantly higher than that of –CF₃ or –SCH₃ alone. The coexistence of the phenolic –OH and –NO₂ groups provides additional handles for chemical transformation, including reduction of the nitro group to an amine, O-alkylation, and condensation reactions.
The molecule's molecular formula is C₇H₄F₃NO₃S, and it belongs to the class of halogenated nitrophenol derivatives widely used as specialty intermediates.
Synthesis Relevance and Reactivity
The phenolic hydroxyl group in 2-Nitro-4-((trifluoromethyl)thio)phenol is a versatile functional handle. It can undergo O-alkylation with alkyl halides under basic conditions to form aryl ethers, or react with acyl chlorides and anhydrides to yield esters. These transformations are particularly useful when constructing more complex molecular architectures for drug discovery programs.
The ortho-nitro group is amenable to selective reduction using standard reagents such as iron/acetic acid, tin(II) chloride, or catalytic hydrogenation, generating the corresponding ortho-aminophenol derivative. This amine can then participate in cyclization reactions to form benzoxazoles, benzimidazoles, or other heterocyclic systems of pharmacological interest.
The –SCF₃ group is generally stable under most reaction conditions, surviving reductions, mild acidic workup, and coupling reactions, making it an ideal tag to incorporate early in a synthetic sequence. Researchers should, however, avoid strongly nucleophilic or strongly basic conditions that could potentially cleave the C–S bond.
Applications in Pharmaceutical and Agrochemical Research
Compounds bearing the –SCF₃ group have attracted growing interest in both the pharmaceutical and agrochemical industries. In medicinal chemistry, the –SCF₃ moiety is exploited to improve membrane permeability, increase metabolic stability, and fine-tune the physicochemical profile of drug candidates. 2-Nitro-4-((trifluoromethyl)thio)phenol serves as a key building block for synthesizing such SCF₃-containing target molecules.
In agrochemical research, trifluoromethylthio-substituted aromatic compounds have been incorporated into fungicides, insecticides, and herbicides, where the fluorinated group contributes to bioavailability and environmental persistence profiles. The nitrophenol scaffold is itself a recognized pharmacophore in several classes of bioactive molecules.
Beyond direct biological applications, this compound can act as a precursor in the preparation of labeled compounds, cross-coupling substrates, or ligands for coordination chemistry when further functionalized.
Safety, Handling, and Storage
As with all nitroaromatic and organofluorine reagents, 2-Nitro-4-((trifluoromethyl)thio)phenol should be handled with appropriate personal protective equipment, including chemical-resistant gloves, safety goggles, and a lab coat. Operations should be conducted in a well-ventilated fume hood to minimize inhalation exposure to dust or vapors.
The compound should be stored in a tightly sealed container, away from heat, open flames, and incompatible materials such as strong oxidizers and strong bases. Cool, dry storage conditions are recommended to maintain reagent integrity over time.
Users should consult the Safety Data Sheet (SDS) provided by Aladdin Scientific for complete hazard classifications, first-aid measures, disposal guidance, and regulatory information before use. All waste should be disposed of in accordance with local institutional and governmental regulations for halogenated organic waste.
Frequently asked questions
What is the primary use of 2-Nitro-4-((trifluoromethyl)thio)phenol in research?
It is primarily used as a specialty aromatic intermediate and building block in pharmaceutical and agrochemical synthesis, particularly for constructing molecules that incorporate the lipophilicity-enhancing –SCF₃ group alongside reducible nitro or phenolic functionalities.
Can the nitro group in this compound be selectively reduced to an amine?
Yes, the nitro group can be selectively reduced to an amine using standard reducing systems such as iron/acetic acid, tin(II) chloride in ethanol, or catalytic hydrogenation. The resulting ortho-aminophenol intermediate is valuable for subsequent heterocycle-forming cyclization reactions.
Why is the –SCF₃ group considered valuable in drug discovery?
The trifluoromethylthio (–SCF₃) group significantly increases the lipophilicity of a molecule, which can improve membrane permeability and oral bioavailability. It also tends to enhance metabolic stability compared to non-fluorinated thioether analogs, making it an attractive bioisostere in lead optimization campaigns.
How should this compound be stored to ensure stability?
Store 2-Nitro-4-((trifluoromethyl)thio)phenol in a tightly sealed container under cool, dry conditions, away from heat, strong oxidizers, and strong bases. Always refer to the Aladdin Scientific SDS for specific storage temperature recommendations and shelf-life guidance.
References
- Meanwell, N. A. Fluorine and fluorinated motifs in the design and application of bioisosteres for drug design. Journal of Medicinal Chemistry, 2018.
- Ilardi, E. A.; Vitaku, E.; Njardarson, J. T. Data-mining for sulfur and fluorine: an evaluation of pharmaceuticals to reveal opportunities for drug design. Journal of Medicinal Chemistry, 2014.
- Aladdin Scientific. Product page: 2-Nitro-4-((trifluoromethyl)thio)phenol, SKU N731573.
Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.
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