(4-((4-(Trifluoromethoxy)phenoxy)methyl)phenyl)boronic Acid: Key Facts
(4-((4-(Trifluoromethoxy)phenoxy)methyl)phenyl)boronic Acid: Key Facts
(4-((4-(Trifluoromethoxy)phenoxy)methyl)phenyl)boronic acid(contains varying amounts of Anhydride) is a fluorinated arylboronic acid building block widely used as a coupling partner in palladium-catalyzed cross-coupling reactions and as a versatile intermediate in medicinal and materials chemistry research.
- SKU
- P728696
- Chemical Name
- (4-((4-(Trifluoromethoxy)phenoxy)methyl)phenyl)boronic acid (contains varying amounts of Anhydride)
- Key Functional Groups
- Boronic acid (–B(OH)₂), trifluoromethoxy (–OCF₃), aryl ether (–O–)
- Anhydride Content
- Contains varying amounts of boroxine anhydride; purity assessment should account for anhydride fraction
- Primary Application
- Suzuki–Miyaura cross-coupling, medicinal chemistry synthesis, materials science
- Storage Recommendation
- Store in a cool, dry place away from moisture; seal tightly after use
Chemical Identity and Structure
(4-((4-(Trifluoromethoxy)phenoxy)methyl)phenyl)boronic acid is an arylboronic acid featuring a para-substituted benzyloxy linker connecting a 4-(trifluoromethoxy)phenyl group to the boronic-acid-bearing phenyl ring. The molecule thus combines three distinct chemical motifs: a reactive boronic acid group capable of covalent and reversible interactions, an aryl ether linkage providing conformational flexibility, and a trifluoromethoxy (–OCF₃) substituent that imparts strong electron-withdrawing character and enhanced metabolic stability to derived compounds.
As is common with arylboronic acids, this compound may partially or fully dehydrate to form the corresponding boroxine (cyclic anhydride, B₃O₃ core) under ambient conditions, particularly upon prolonged storage or exposure to low humidity. The label notation contains varying amounts of Anhydride reflects this equilibrium. In aqueous or protic media the anhydride readily reverts to the free boronic acid, so its presence does not typically diminish synthetic utility.
Applications in Synthetic Chemistry
Suzuki–Miyaura Cross-Coupling: Arylboronic acids are cornerstone reagents in palladium-catalyzed Suzuki–Miyaura reactions, enabling the formation of biaryl and aryl–heteroaryl carbon–carbon bonds under mild conditions. (4-((4-(Trifluoromethoxy)phenoxy)methyl)phenyl)boronic acid can serve as the organoboron coupling partner with aryl or vinyl halides and pseudohalides, delivering trifluoromethoxy-functionalized biaryl products relevant to pharmaceutical and agrochemical programs.
Medicinal Chemistry: The –OCF₃ group is a prized bioisostere in drug design, modulating lipophilicity (logP), membrane permeability, and resistance to oxidative metabolism. Incorporation of this motif via boronic-acid-based coupling facilitates the rapid assembly of fluorinated scaffolds for structure–activity relationship (SAR) studies.
Materials and Supramolecular Chemistry: Boronic acids reversibly bind diols, enabling dynamic covalent frameworks, sensors for saccharides, and stimuli-responsive polymers. The fluorinated aryl ether backbone of this compound may additionally contribute useful dielectric or optical properties in materials applications.
Handling, Storage, and Purity Considerations
Anhydride Equilibrium: Because this product contains varying amounts of the boroxine anhydride, researchers should be aware that the nominal molecular weight of the free boronic acid (MW ≈ 312.09 g/mol) differs from that of the trimeric anhydride. When preparing stock solutions or calculating stoichiometry, it is advisable to verify effective boronic acid content by ¹H NMR or titration, or to use an excess relative to the nominal mass.
Moisture Sensitivity: Although boronic acids are not acutely moisture-sensitive, prolonged exposure to humid air can promote hydrolysis products or physical clumping. Store in a sealed vial under inert atmosphere or with a desiccant. Refrigeration (2–8 °C) is generally recommended for long-term stability.
Safety: Handle with standard laboratory precautions: use appropriate personal protective equipment (gloves, safety glasses, lab coat). Consult the Safety Data Sheet (SDS) provided by Aladdin Scientific before use. Avoid inhalation of dust and contact with skin or eyes. Dispose of waste in accordance with local regulations.
Reagent Specification and Quality Assurance
Aladdin Scientific supplies (4-((4-(Trifluoromethoxy)phenoxy)methyl)phenyl)boronic acid under SKU P728696. As with all Aladdin boronic acid reagents, the product undergoes quality control analysis to confirm chemical identity and assess purity. Because the anhydride content is variable, lot-specific certificates of analysis (CoA) are available and should be consulted for precise purity values before initiating sensitive synthetic procedures.
Researchers requiring high-purity material free of anhydride may consider recrystallization from water or aqueous organic solvent mixtures, which hydrolyzes the boroxine back to the monomeric boronic acid. Alternatively, storing the solid reagent over a mild humidifying agent can maintain the compound predominantly in the free acid form.
Frequently asked questions
Why does this boronic acid contain varying amounts of anhydride, and does it affect my reaction?
Arylboronic acids readily dehydrate to form cyclic trimeric boroxines (anhydrides) under dry conditions; the equilibrium shifts back to the free boronic acid in the presence of water or protic solvents. In most Suzuki–Miyaura or other cross-coupling reactions run in aqueous or mixed aqueous/organic media, the anhydride is hydrolyzed in situ and does not negatively affect yield. However, for precise stoichiometric calculations, consult the lot CoA or determine the effective boronic acid content by NMR.
What reaction conditions are typically used for Suzuki–Miyaura coupling with this reagent?
Typical Suzuki–Miyaura conditions employ a palladium catalyst (e.g., Pd(PPh₃)₄, Pd(dppf)Cl₂, or Pd₂(dba)₃ with a phosphine ligand), an inorganic base (e.g., K₂CO₃, Cs₂CO₃, or Na₂CO₃), and a mixed aqueous/organic solvent system (e.g., DMF/H₂O, dioxane/H₂O, or EtOH/H₂O) at temperatures ranging from room temperature to 100 °C. Specific optimization may be required depending on the aryl halide coupling partner and desired product.
How should I store SKU P728696 to maximize shelf life?
Store the compound in a tightly sealed container under an inert atmosphere (nitrogen or argon) in a cool, dry location, ideally at 2–8 °C with a desiccant. Avoid repeated freeze–thaw cycles and prolonged exposure to air or moisture. Under these conditions, the reagent should remain stable for an extended period; refer to the product label and CoA for the manufacturer's recommended shelf life.
Is this compound suitable for medicinal chemistry fragment-based screening?
Yes. Fluorinated arylboronic acids, including those bearing –OCF₃ groups, are valuable in fragment-based drug discovery (FBDD) due to the metabolic stability and lipophilicity-modulating effects of fluorine substituents. The boronic acid moiety itself can also serve as a pharmacophore targeting serine proteases or other enzymes with active-site residues capable of forming reversible covalent adducts with boron.
References
- Miyaura, N.; Suzuki, A. Palladium-Catalyzed Cross-Coupling Reactions of Organoboron Compounds. Chem. Rev. 1995, 95, 2457–2483. doi:10.1021/cr00039a007
- Hall, D. G. (Ed.) Boronic Acids: Preparation and Applications in Organic Synthesis, Medicine and Materials, 2nd ed.; Wiley-VCH: Weinheim, 2011.
- Purser, S.; Moore, P. R.; Swallow, S.; Gouverneur, V. Fluorine in medicinal chemistry. Chem. Soc. Rev. 2008, 37, 320–330. doi:10.1039/b610213c
Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.
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