Production Method 1

139301-27-2

828-27-3

Reaction Conditions

1.1 Reagents: Oxygen Catalysts: Iron oxide (Fe2O3) Solvents: Tetrahydrofuran ;  rt
1.2 Reagents: Water

Reference

Ligand- and base-free synthesis of phenols by rapid oxidation of arylboronic acids using iron(III) oxide

Sawant, Sanghapal D.; et al, Tetrahedron Letters, 2014, 55(4), 811-814

Production Method 2

2035508-27-9

828-27-3

Reaction Conditions

1.1 Reagents: Water Catalysts: Sodium cyanide Solvents: Ethanol ;  12 h, 50 °C

Reference

An efficient and chemoselective deprotection of aryl tert-butyldimethylsilyl (TBDMS) ethers by NaCN

Qiao, Xue-jun; et al, Journal of the Brazilian Chemical Society, 2016, 27(5), 899-904

Production Method 3

1800-70-0

828-27-3

Reaction Conditions

1.1 Reagents: Sodium hydroxide Solvents: Water

Reference

Preparation of (trifluoromethoxy)phenols from bis[(trifluoromethoxy)phenyl] carbonates

, Japan, , ,

Production Method 4

37181-39-8

828-27-3

Reaction Conditions

1.1 Reagents: Sodium acetate ,  Water Catalysts: Cuprous chloride Solvents: Dimethylformamide ;  2 h, 40 °C

Reference

Copper-catalyzed synthesis of phenol and diaryl ether derivatives via hydroxylation of diaryliodoniums

Ye, Lianbao; et al, RSC Advances, 2019, 9(37), 21525-21529

Production Method 5

828-27-3

Reaction Conditions

1.1 Reagents: Cesium fluoride Solvents: Dimethylformamide ;  1 h, 60 °C

Reference

2-(Trimethylsilyl)ethanol as a new alcohol equivalent for copper-catalyzed coupling of aryl iodides

Dibakar, Mullick; et al, Tetrahedron Letters, 2011, 52(41), 5338-5341

Production Method 6

407-14-7

828-27-3

Reaction Conditions

1.1 Reagents: Dabco ,  Water Catalysts: Nickel dichloride ,  2,4,5,6-Tetrakis(diphenylamino)-1,3-benzenedicarbonitrile Solvents: 1,3-Dimethyl-2-imidazolidinone ;  3 h, rt

Reference

Machine-Learning Classification for the Prediction of Catalytic Activity of Organic Photosensitizers in the Nickel(II)-Salt-Induced Synthesis of Phenols

Noto, Naoki ; et al, Angewandte Chemie, 2023, 62(11),

Production Method 7

139301-27-2

828-27-3

Reaction Conditions

1.1 Reagents: Hydrogen peroxide Catalysts: Povidone-iodine Solvents: Water ;  25 °C

Reference

A practical method for preparation of phenols from arylboronic acids catalyzed by iodopovidone in aqueous medium

Lu, Guangying; et al, Tetrahedron Letters, 2019, 60(39),

Production Method 8

139301-27-2

828-27-3

Reaction Conditions

1.1 Reagents: Potassium hydroxide ,  Oxygen Catalysts: Quinone Solvents: Water ;  23 h, reflux
1.2 Reagents: Hydrochloric acid Solvents: Water

Reference

Benzoquinone-promoted aerobic oxidative hydroxylation of arylboronic acids in water

Cheng, Guolin; et al, Synthesis, 2014, 46(3), 295-300

Production Method 9

37181-39-8

828-27-3

Reaction Conditions

1.1 Reagents: Water ,  Vitreous silica Catalysts: N-Benzyl-2-pyridone Solvents: Chlorobenzene ;  36 h, 105 °C

Reference

Organocatalytic Synthesis of Phenols from Diaryliodonium Salts with Water under Metal-Free Conditions

Katagiri, Kotone; et al, Organic Letters, 2022, 24(28), 5149-5154

Production Method 10

659-28-9

828-27-3

Reaction Conditions

1.1 Reagents: m-Chloroperbenzoic acid

Reference

(2R)-2-Methylchromane-2-carboxylic acids: Discovery of selective PPARα agonists as hypolipidemic agents

Koyama, Hiroo; et al, Bioorganic & Medicinal Chemistry Letters, 2005, 15(14), 3347-3351

Production Method 11

330-12-1

828-27-3

Reaction Conditions

1.1 Reagents: Sodium fluoride ,  Lithium perchlorate ,  Bis(pinacolato)diborane ,  N-Fluorobenzenesulfonimide Catalysts: Tetrakis(acetonitrile)copper(1+) tetrafluoroborate Solvents: Acetonitrile ;  6 h
1.2 Reagents: Sodium peroxoborate ,  Oxygen Solvents: Tetrahydrofuran ,  Water ;  1 h, rt
1.3 Reagents: Ammonium chloride Solvents: Water ;  rt

Reference

Decarboxylative Borylation and Cross-Coupling of (Hetero)aryl Acids Enabled by Copper Charge Transfer Catalysis

Dow, Nathan W.; et al, Journal of the American Chemical Society, 2022, 144(14), 6163-6172

Production Method 12

461-82-5

828-27-3

Reaction Conditions

1.1 Reagents: Sodium nitrite ,  Sulfuric acid

Reference

Modifications of primaquine as antimalarials. 3. 5-Phenoxy derivatives of primaquine

Nodiff, Edward A.; et al, Journal of Medicinal Chemistry, 1982, 25(9), 1097-101

Production Method 13

2916-68-9

103962-05-6

828-27-3

Reaction Conditions

1.1 Reagents: Cesium carbonate Catalysts: 1,10-Phenanthroline ,  Cuprous iodide Solvents: Toluene ;  14 h, 110 °C; 110 °C → rt
2.1 Reagents: Cesium fluoride Solvents: Dimethylformamide ;  1 h, 60 °C

Reference

2-(Trimethylsilyl)ethanol as a new alcohol equivalent for copper-catalyzed coupling of aryl iodides

Dibakar, Mullick; et al, Tetrahedron Letters, 2011, 52(41), 5338-5341

Production Method 14

14874-70-5

1493-13-6

828-27-3

Reaction Conditions

1.1 Solvents: Dichloromethane ;  0 °C; 0 °C; 15 min, rt
2.1 Reagents: Water ,  Vitreous silica Catalysts: N-Benzyl-2-pyridone Solvents: Chlorobenzene ;  36 h, 105 °C

Reference

Organocatalytic Synthesis of Phenols from Diaryliodonium Salts with Water under Metal-Free Conditions

Katagiri, Kotone; et al, Organic Letters, 2022, 24(28), 5149-5154

Production Method 15

828-27-3

98-86-2

Reaction Conditions

1.1 Catalysts: Palladium Solvents: Ethanol ,  Water ;  6 h, 120 °C

Reference

Catalytic C-O bond cleavage in a β-O-4 lignin model through intermolecular hydrogen transfer

Ahsan Usman, Muhammad; et al, Inorganica Chimica Acta, 2021, 521,

4-(Trifluoromethoxy)phenol Raw materials

• 1-Bromo-4-(trifluoromethoxy)benzene
• 4-(Trifluoromethoxy)benzaldehyde
• Phenol, 4-(trifluoromethoxy)-, carbonate (2:1)
• tert-Butyldimethyl-(4-(trifluoromethoxy)phenoxy)silane
• Borate(1-),tetrafluoro-
• 4-(Trifluoromethoxy)aniline
• 2-(Trimethylsilyl)ethanol
• [4-(trifluoromethoxy)phenyl]boronic acid
• Trifluoromethanesulfonic acid
• 1-Iodo-4-(trifluoromethoxy)benzene
• 4-(Trifluoromethoxy)benzoic acid

4-(Trifluoromethoxy)phenol Preparation Products

• 4-(Trifluoromethoxy)phenol (828-27-3)
• Acetophenone (98-86-2)

• 1. Establishment and implications of a characterization method for magnetic nanoparticle using cell tracking velocimetry and magnetic susceptibility modified solutions
  Huading Zhang,Lee R. Moore,Maciej Zborowski,P. Stephen Williams,Shlomo Margel,Jeffrey J. Chalmers Analyst, 2005,130, 514-527
• 2. Emergence of microfluidic wearable technologies
  Joo Chuan Yeo,Kenry Lab Chip, 2016,16, 4082-4090
• 3. Exchangeability of amino acid residues with similar physicochemical properties in coiled-coil interactions?
  Guiying Zhang,Maosheng Cheng,Yanni Li,Keliang Liu,Lifeng Cai Chem. Commun., 2013,49, 11086-11088
• 4. Excellent lithium ion storage property of porous MnCo2O4 nanorods?
  Peiyuan Zeng,Xiaoxiao Wang,Ming Ye,Qiuyang Ma,Jianwen Li,Wanwan Wang,Baoyou Geng,Zhen Fang RSC Adv., 2016,6, 23074-23084
• 5. Fast synthesis of red Li3BaSrLn3(WO4)8:Eu3+ phosphors for white LEDs under near-UV excitation by a microwave-assisted solid state reaction method and photoluminescence studies
  Bo Wei,Zhenyu Liu,Chen Xie,Shu Yang,Wentao Tang,Aiwei Gu,Wing-Tak Wong,Ka-Leung Wong J. Mater. Chem. C, 2015,3, 12322-12327

• Solvents and Organic Chemicals Organic Compounds Benzenoids Phenols 4-alkoxyphenols
• Solvents and Organic Chemicals Organic Compounds Alcohol/Ether
• Solvents and Organic Chemicals Organic Compounds Hydrocarbons

Introduction to 4-(Trifluoromethoxy)phenol (CAS No. 828-27-3)

4-(Trifluoromethoxy)phenol, with the chemical formula C?H?F?O? and CAS number 828-27-3, is a fluorinated aromatic compound that has garnered significant attention in the field of pharmaceutical and agrochemical research. This compound belongs to the class of phenolic derivatives, characterized by the presence of a trifluoromethoxy group attached to a benzene ring. The introduction of fluorine atoms into organic molecules often enhances their metabolic stability, bioavailability, and binding affinity, making 4-(Trifluoromethoxy)phenol a valuable intermediate in the synthesis of various bioactive molecules.

The structural motif of 4-(Trifluoromethoxy)phenol consists of a phenol ring substituted with a trifluoromethoxy group at the para position. This arrangement imparts unique electronic and steric properties to the molecule, influencing its reactivity and interactions with biological targets. The trifluoromethoxy group is known to exhibit strong electron-withdrawing effects through resonance and inductive mechanisms, which can modulate the electronic properties of the aromatic ring. This feature makes 4-(Trifluoromethoxy)phenol a versatile building block for designing molecules with tailored pharmacological profiles.

In recent years, 4-(Trifluoromethoxy)phenol has been extensively studied for its potential applications in drug discovery. The phenolic hydroxyl group in this compound can participate in hydrogen bonding interactions, making it an attractive scaffold for developing molecules that interact with biological macromolecules such as proteins and nucleic acids. Additionally, the fluorinated aromatic system can improve the lipophilicity of drug candidates, enhancing their membrane permeability and cellular uptake.

One of the most compelling aspects of 4-(Trifluoromethoxy)phenol is its role as a precursor in the synthesis of various pharmacologically active compounds. For instance, it has been utilized in the preparation of fluorinated analogs of nonsteroidal anti-inflammatory drugs (NSAIDs), which exhibit improved efficacy and reduced side effects compared to their non-fluorinated counterparts. The introduction of fluorine atoms into NSAID structures has been shown to enhance their binding affinity to cyclooxygenase enzymes (COX-1 and COX-2), leading to more potent anti-inflammatory activity.

Furthermore, 4-(Trifluoromethoxy)phenol has found applications in the development of anticancer agents. Fluorinated phenols have been investigated for their ability to inhibit kinases and other enzymes involved in cancer cell proliferation. Recent studies have demonstrated that compounds derived from 4-(Trifluoromethoxy)phenol can selectively target tumor cells while minimizing toxicity to healthy tissues. This selectivity is attributed to the unique electronic properties of fluorinated aromatic systems, which can enhance binding interactions with specific biological targets over non-fluorinated analogs.

The agrochemical industry has also recognized the potential of 4-(Trifluoromethoxy)phenol as a key intermediate in the synthesis of pesticides and herbicides. Fluorinated phenolic compounds have been shown to exhibit enhanced stability against environmental degradation, improving their effectiveness in controlling pests and weeds. Additionally, these compounds often demonstrate improved selectivity towards target organisms, reducing harm to beneficial flora and fauna.

From a synthetic chemistry perspective, 4-(Trifluoromethoxy)phenol serves as a versatile intermediate for constructing more complex molecular architectures. The presence of both a hydroxyl and a trifluoromethoxy group allows for diverse functionalization strategies, including etherification, esterification, and coupling reactions with other heterocycles. These transformations have enabled the preparation of novel compounds with potential therapeutic applications in areas such as antiviral and antibacterial research.

Recent advancements in computational chemistry have further highlighted the significance of 4-(Trifluoromethoxy)phenol in drug discovery. Molecular modeling studies have revealed that this compound can adopt multiple conformations depending on its environment, influencing its interactions with biological targets. These insights have guided the design of optimized derivatives with improved pharmacokinetic properties.

The environmental impact of using fluorinated compounds like 4-(Trifluoromethoxy)phenol is also an area of growing interest. While these compounds offer numerous advantages in terms of bioactivity and stability, their persistence in the environment raises concerns about potential long-term ecological effects. Ongoing research aims to develop strategies for synthesizing fluorinated derivatives that are both effective and environmentally sustainable.

In conclusion, 4-(Trifluoromethoxy)phenol (CAS No. 828-27-3) is a multifaceted compound with significant potential in pharmaceutical and agrochemical applications. Its unique structural features make it an invaluable intermediate for synthesizing bioactive molecules with enhanced efficacy and selectivity. As research continues to uncover new applications for this compound, it is likely to remain a cornerstone in medicinal chemistry for years to come.

• 142990-39-4(Benzene, trifluoromethoxy-)
• 169222-42-8((4-(Trifluoromethoxy)phenyl)magnesium bromide, 0.50 M in THF)
• 142990-38-3(Benzene, difluoromethoxy-)
• 142738-94-1(1-methoxy-3-(trifluoromethoxy)benzene)
• 827-99-6(3-(Trifluoromethoxy)phenol)
• 87789-47-7(4-(Difluoromethoxy)phenol)
• 456-55-3((Trifluoromethoxy)benzene)
• 710-18-9(4-(Trifluoromethoxy)anisole)
• 458-92-4((Difluoromethoxy)benzene)
• 552332-04-4((3-(Trifluoromethoxy)phenyl)magnesium bromide, 0.50 M in THF)